MINOCYCLINE, ALZHEIMER'S, AND OTHER NEUROLOGICAL DISORDERS. / LA MINOCICLINA, EL ALZHEIMER, Y OTROS TRASTORNOS NEUROLOGICOS.

The Minocycline, new uses for an old antibiotic, update.!!

La minociclina, nuevos usos para un viejo antibiótico, actualización. !! 

 

 

EDITORIAL ENGLISH

 ==================

Hello again DERMAGIC friends, today with this interesting topic on the MINOCYCLINE. Minocycline Belongs to the second generation class of cyclines, member of the tetracycline class. It was synthesized in 1967 and marketed in 1972. 

Minocycline has an antiinfectious activity with a spectrum similar to that of other cyclines, notably against Chlamydias, Treponema and Proprionibacterium acnes, An old antibiotic that through time has been discovered beneficial properties in some diseases that perhaps you never imagined.

This publication was launched to the net a few years ago under the title of THE MINOCYCLINE, THE GOOD THE BAD AND THE UGLY. This medicine has been discovered beneficial properties in diseases for which was not created or launched to the market, such is the case of LEPRA, which describes its BACTERICIDE effect On Mycobacterium Leprae. Mainly this drug has been, was and is used for acne treatment. But little Soon the range of its use was extended.

Today I bring you this update, to draw the attention of all readers in the sense that this "old" medicine today is described anti-inflammatory and neuroprotective properties in neurological diseases, among Which highlight ALZHEIMER'S DISEASE AND SCHIZOPHRENIA. (References 31-53)
 

 

 THE GOOD:

 ==========

 

 This popular medication will have beneficial effects on disease like:

 

 1.) LEPROSY (MYCOBACTERIUM LEPRAE)

 2.) SCLERODERMA.

 3.) PEMPHIGUS.

 4.) PYODERMA GANGRENOSUM.

 5.) CICATRICIAL PEMPHIGOID

 6.) RETICULATED PAPILLOMATOSIS.

 7.) LYME DISEASE (ERYTHEMA MIGRANS)

 8.) ACNE

 9.) CHLAMYDIAS

 10.) TREPONEMA

 11.) MYCOBATERIUM KANSAII

 12.) PULMONARY NOCARDIOSIS.

 12.) BLASTOMYCOSIS.

 13.) RHEUMATOID ARTHRITIS.

 14.) HEPATIC CYSTS and OTHERS.

 

The most interesting of the subject on the MINOCYCLINE is its use in neorological disorders discovering neoroprotector effects. Minocycline has been found to have beneficial effects on inflammation, microglial activation, nitric oxide production, and apoptotic cell death into the central nervous system, and is being used in diseases such as:

 

 1.) ALZHEIMER'S DISEASE.

 2.) PARKINSON'S DISEASE

 3.) MULTIPLE SCLEROSIS.

 4.) BIPOLAR DISORDERS.

 5. SCHIZOPHRENIA.

 6.) AUTOINMUNE ENCEPHALOMYELITIS.

 

 Who was going to think that this old antibiotic that has more than 40 years in the market, today is being used in diseases such as Alzheimer's and schizophrenia.

The big question is? Minocycline could be used to provoke neuroprotection or to improve the inflammatory state in these neurological disorders at a minimal dose to avoid side effects ?. The only way to know this is through more studies about it.

It would also be interesting to know what level of neuroprotection developed those patients who took minocycline in the long term for the treatment of acne.
  

 

 THE BAD AND THE UGLY:

 ======================

 As all medicines Minocycline have their adverse effects, Among them lupus, vasculitis and otrers.

 
This publication, (updated today) was launched a few years ago under the name of THE MINOCYCLINE, THE GOOD, BAD AND THE UGLY ... and was a total success, to the point that was published in the DERMATOLOGIC magazine of CHILE... And today, this antibiotic continues to show NEW positive properties.

The facts in these 73 references !!

 

 greetings to all !!!

 

 Dr. Jose Lapenta.

 EDITORIAL ESPAÑOL
 ==================
 Hola de nuevo amigos DERMAGICOS, hoy con este interesante tema sobre la MINOCICLINA. La Minociclina pertenece a la segunda generación de ciclinas, miembro de las tetraciclinas. Se sintetizó en 1967 y se comercializó en 1972. 

La Minociclina tiene una actividad antiinfecciosa con un espectro similar al de otras ciclinas, especialmente contra Clamidias, Treponema y Proprionibacterium acnes. Un  antiguo antibiótico que a través del tiempo se le han descubierto propiedades beneficiosas en algunas enfermedades que tal vez nunca imaginaste.

Esta publicacion fue lanzada a la red hace unos años bajo el titulo de LA MINOCICLINA, LO BUENO LO MALO Y LO FEO. A Esta medicina se le han descubierto propiedades beneficiosas en enfermedades para las cuales no fue creada ni lanzada el mercado, tal es el caso de la LEPRA, donde se describe su efecto BACTERICIDA sobre el Mycobacterium Leprae. Principalmente esta droga ha sido, fue y es usada para e tratamiento del acne. Pero poco a poco se fue extendiendo el rango de sus uso.

 Hoy se las traigo actualizada, para llamar la atencion de todos los lectores en el sentido de que a esta ¨vieja¨ medicina hoy dia se le describen propiedades antiinflamatorias y neuroprotectoras en enfermedades neurologicas, entre las que destacan la ENFERMEDAD DE ALZHEIMER Y LA ESQUIZOFRENIA. (referencias 31 -53)

LO BUENO:
==========
 Este medicamento popular tiene efectos beneficiosos sobre enfermedades como:

 1.) LEPRA (MYCOBACTERIUM LEPRAE)
 2.) ESCLERODERMIA.
 3.) PEMFIGO.
 4.) PYODERMA GANGRENOSO.
 5.) PEMFIGOIDE CICATRICIAL
 6.) PAPILOMATOSIS RETICULADA.
 7.) ENFERMEDAD DE LYME (ERITEMA MIGRANS)
 8.) ACNE
 9.) CHLAMYDIA
 10.) TREPONEMA
 11.) MYCOBATERIUM KANSAII
 12.) NOCARDIOSIS PULMONAR.
 12.) BLASTOMICOSIS.
 13.) ARTRITIS REUMATOIDE.
 14.) QUISTES HEPATICOS y OTROS.

 Pero lo más interesante del tema sobre la MINOCICLINA es su uso en desórdenes neorológicos, descubriendose efectos neoroprotectores. Se ha descubierto que la minociclina tiene efectos beneficiosos sobre la inflamación, la activación microglial, la producción de óxido nítrico y la muerte celular apoptótica en el sistema nervioso central y se utiliza en enfermedades tales como:

 1.) ENFERMEDAD DE ALZHEIMER.
 2.) ENFERMEDAD DE PARKINSON
 3.) ESCLEROSIS MÚLTIPLE.
 4.) TRASTORNOS BIPOLARES.
 5.) ESQUIZOFRENIA.
 6.) ENCEFALOMIELITIS AUTOINMUNE.

 ¿Quién iba a pensar que este viejo antibiótico que tiene más de 40 años en el mercado, hoy está siendo utilizado en enfermedades como el Alzheimer y la esquizofrenia.


La gran pregunta es ? podria utilizarse la minociclina para provocar neuroprotecccion o mejorar el estado inflamatorio en estos desordenes neurologicos, a dosis minima para evitar efectos secundarios.? La unica manera de saberlo es mediante mas estudios al respecto.

Tambien seria interesante conocer que nivel de neuroproteccion desarrollaron aquellos pacientes que tomaron minociclina a largo plazo para el tratamiento del acne.

 LO MALO Y LO FEO:
 ==================
 Como todos los medicamentos la Minociclina tiene sus efectos adversos, dstacan el lupus, vasculitis y otros.

Esta publicacion (hoy actualizada), hace unos años fue lanzada a la red bajo el nombre de La MINOCICLINA, LO BUENO, LO MALO Y LO FEO... y fue un exito total, al punto que fue publicada en la REVISTA DERMATOLOGICA DE CHILE...y hoy dia, este antibiotico sigue mostrando NUEVAS  propiedades positivas.

Los hechos en estas 73 referencias !!

 saludos a todos !!!

 Dr. Jose Lapenta R.
 
====================================================================== REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES
====================================================================== ====================================================================== ()()()()()()()()()()()()LO BUENO () THE GOOD ()()()()()()()()()()()()()() 
=========================================================================
1.) Superior antibacterial action and reduced incidence of bacterial
resistance in minocycline compared to tetracycline-treated acne patients.
2.) Tetracycline-resistant propionibacteria from acne patients are
cross-resistant to doxycycline, but sensitive to minocycline.
3.) Research letters : Minocycline in early diffuse scleroderma
4.) Minocycline in lepromatous leprosy.
5.) Efficacy of minocycline in single dose and at 100 mg twice daily for
lepromatous leprosy.
6.) Field trial on efficacy of supervised monthly dose of 600 mg rifampin,
400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first
results.
7.) Bactericidal activity of a single-dose combination of ofloxacin plus
minocycline, with or without rifampin, against Mycobacterium leprae in mice
and in lepromatous patients.
8.) Efficacy of single dose multidrug therapy for the treatment of
single-lesion paucibacillary leprosy. Single-lesion Multicentre Trial Group.
9.) Bactericidal activity of single dose of clarithromycin plus
minocycline, with or without ofloxacin, against Mycobacterium leprae in
patients.
10.) WHO Expert Committee on Leprosy.
11.) Experimental evaluation of possible new short-term drug regimens for
treatment of multibacillary leprosy.
12.) Powerful bactericidal activities of clarithromycin and minocycline
against Mycobacterium leprae in lepromatous leprosy.
13.) Minocycline is a useful adjuvant therapy for pemphigus.
14.) Confluent and reticulated papillomatosis: response to minocycline.
15.) Minocycline treatment for confluent and reticulated papillomatosis.
16.) No detection of Borrelia burgdorferi-specific DNA in erythema migrans
lesions after minocycline treatment.
17.) Minimizing cicatricial pemphigoid orodynia with minocycline.
18.) Response of atypical bullous pyoderma gangrenosum to oral minocycline
hydrochloride and topical steroids.
19.) Blastomycosis-like pyoderma--report of a case responsive to
combination therapy utilizing minocycline and carbon dioxide laser
debridement.
20.) A sporotrichoid-like Mycobacterium kansasii infection of the skin
treated with minocycline hydrochloride.
21.) Primary lymphocutaneous nocardiosis due to Nocardia otitidiscaviarum:
the first case report from Japan.
22.) Minocycline treatment of pulmonary nocardiosis.
23.) Minocycline in rheumatoid arthritis. A 48-week, double-blind,
placebo-controlled trial. MIRA Trial Group [see comments]
24.) Minocycline prevents the decrease in bone mineral density and
trabecular bone in ovariectomized aged rats.
25.) Minocycline and cefotaxime in the treatment of experimental murine
Vibrio vulnificus infection.
26.) The role of minocycline in the treatment of intracranial 9L glioma.
27.) Evaluation of the long-term efficacy and safety of locally-applied
minocycline in adult periodontitis patients.
28.) Clinical and microbiological effects of minocycline-loaded
microcapsules in adult periodontitis.
29.) The broad-spectrum activity and efficacy of catheters coated with
minocycline and rifampin.
30.) Symptomatic hepatic cysts: treatment with single-shot injection of
minocycline hydrochloride 31.) Systematic review and meta-analysis of the efficacy and safety of minocycline in schizophrenia.
32.) Adjunctive minocycline for schizophrenia: A meta-analysis of randomized controlled trials.
33.) Minocycline as an adjunct for treatment-resistant depressive symptoms: study protocol for a pilot randomised controlled trial.
34.) Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2x2 clinical trial.
35.) Interferon β-secreting mesenchymal stem cells combined with minocycline attenuate experimental autoimmune encephalomyelitis.
36.) Glatiramer acetate in combination with minocycline in patients with relapsing--remitting multiple sclerosis: results of a Canadian, multicenter, double-blind, placebo-controlled trial.
37.) The Anti-Inflammatory Role of Minocycline in Alzheimer´s Disease.
38.) Discovering new treatments for Alzheimer's disease by repurposing approved medications.
39.) Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder.
40.) Anti-apoptotic and anti-oxidative mechanisms of minocycline against sphingomyelinase/ceramide neurotoxicity: implication in Alzheimer's disease and cerebral ischemia.
41.) Clinical potential of minocycline for schizophrenia.
42.) The potential of minocycline for neuroprotection in human neurologic disease.
43.) Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis.
44.) The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the Lyme disease spirochete Borrelia burgdorferi.
45.)[Minocycline].
46.) Minocycline attenuates neuronal cell death and improves cognitive impairment in Alzheimer's disease models.
 47.) Minocycline and neurodegenerative diseases.
48.) Minocycline attenuates Aβ oligomers-induced pro-inflammatory phenotype in primary microglia while enhancing Aβ fibrils phagocytosis.
49) Discovering new treatments for Alzheimer's disease by repurposing approved medications.
50.) Anti-apoptotic and anti-oxidative mechanisms of minocycline against sphingomyelinase/ceramide neurotoxicity: implication in Alzheimer's disease and cerebral ischemia.
 51.) Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology.
 52.) Reductions in amyloid-beta-derived neuroinflammation, with minocycline, restore cognition but do not significantly affect tau hyperphosphorylation.
 53.) Minocycline may be useful to prevent/treat postoperative cognitive decline in elderly patients.
==================================================================== ====================================================================
1.) Superior antibacterial action and reduced incidence of bacterial
resistance in minocycline compared to tetracycline-treated acne patients.
====================================================================
ARTICLE SOURCE: Br J Dermatol (England), Feb 1990, 122(2) p233-44
AUTHOR(S): Eady EA; Cove JH; Holland KT; Cunliffe WJ
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Twenty-five previously untreated acne patients were monitored
throughout a 6-month course of therapy with either tetracycline or
minocycline for changes in the numbers of staphylococci, propionibacteria
and yeasts of the genus Malessezia on the skin surface. Antibiotic
resistant staphylococci and propionibacteria were also counted. Minocycline
(50 mg b.d.) produced a 10-fold greater reduction in propionibacterial
numbers compared to tetracycline (500 mg b.d.) after 12 (P less than 0.02,
t-test) and 24 weeks (P less than 0.05) of therapy. As treatment
progressed, propionibacteria were replaced by yeasts, numbers of which were
significantly increased by week 12 (P less than 0.02) in
tetracycline-treated patients and by week 24 (P less than 0.01) in
minocycline-treated patients. This suggests that yeasts have no role in the
pathogenesis of acne but may compete with propionibacteria for the same
niche. Overgrowth of antibiotic resistant staphylococci prevented any
decrease in staphylococcal numbers in tetracycline-treated patients, but
minocycline produced a significant and sustained reduction in
staphylococcal numbers after 1 week of therapy (P less than 0.001). An
increase in the number of multiply resistant (greater than or equal to 3
resistances) staphylococci occurred in 67% of tetracycline-treated and 33%
of minocycline-treated patients by the end of the treatment period. There
was no evidence of propionibacterial resistance in either treatment group.
This study shows that minocycline has much greater antibacterial activity
in vivo against both staphylococci and propionibacteria and produces less
staphylococcal antibiotic resistance than tetracycline. 
=========================================================================
2.) Tetracycline-resistant propionibacteria from acne patients are
cross-resistant to doxycycline, but sensitive to minocycline.
=========================================================================
ARTICLE SOURCE: Br J Dermatol (England), May 1993, 128(5) p556-60
AUTHOR(S): Eady EA; Jones CE; Gardner KJ; Taylor JP; Cove JH; Cunliffe WJ
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Antibiotic-resistant propionibacteria are being isolated with
increasing frequency from antibiotic-treated acne patients. Minimum
inhibitory concentrations (MICs) of three tetracyclines, extensively used
in acne therapy, were determined for 46 resistant and 19 sensitive
propionibacteria isolates. Sensitive strains were inhibited by or = 1
microgram/ml of all three tetracyclines. For every resistant strain tested,
the MIC of tetracycline exceeded that of doxycycline which, in turn,
exceeded that of minocycline. The mean MIC for resistant strains was 20.61
+/- 4.56 micrograms/ml of tetracycline, 9.70 +/- 2.03 micrograms/ml of
doxycycline and 1.95 +/- 0.35 micrograms/ml of minocycline. In order to
determine whether these strains could be inhibited by concentrations of
minocycline achievable in vivo, serum levels of minocycline were determined
in acne patients receiving either the recommended dose of 50 mg b.d. (20
males, 14 females), or twice this dose (21 males, 12 females). Serum levels
were significantly higher (P 0.001, Student's t-test) in patients receiving
100 mg b.d. Males on 50 mg b.d. had significantly lower serum levels than
females on the same dose (P 0.05. Student's t-test). For all patients, the
mean serum level on high-dose minocycline was 2.46 +/- 0.45 micrograms/ml,
compared with 1.38 +/- 0.30 micrograms/ml on the smaller dose. These
results indicate that tetracycline-resistant propionibacteria should be
considered clinically minocycline sensitive, if patients who harbour such
strains are prescribed 100 mg b.d. The recommended dose of minocycline for
treating acne, especially in male patients, should be re-assessed. 
=========================================================================
3.) Research letters : Minocycline in early diffuse scleroderma
=========================================================================
The Lancet 1998;352(9142):1755-6
Minocycline may effectively treatearly diffuse scleroderma. 11 patients in
the early stages of skin disease treated in open-label fashion for up to one
year with minocycline. Six patients completed the study, of whom four had
complete resolution of disease. 
=========================================================================
4.) Minocycline in lepromatous leprosy.
=========================================================================
Author
Fajardo TT Jr; Villahermosa LG; dela Cruz EC; Abalos RM; Franzblau SG;
Walsh GP
Address
Clinical Research Branch, Leonard Wood Memorial Center, Cebu City, The
Philippines.
Source
Int J Lepr Other Mycobact Dis, 63(1):8-17 1995 Mar
Abstract
Twelve patients were treated with three dose levels of minocycline for 30
days, primarily to detect the dose-related effects on Mycobacterium leprae
viability, followed by another 5 months of daily minocycline for overall
efficacy and persistence of clinical and antibacterial effects.
Subsequently, the patients were given standard WHO/MDT chemotherapy for
multibacillary leprosy. Clinical improvement was recognizable during the
first month, occurring much earlier among those on minocycline 200 mg daily
than those who received minocycline 100 mg daily. A similar change also was
observed in one patient 11 days after three daily doses of 100 mg of
minocycline. At the end of 6 months, all patients were clinically improved
with a slight reduction in the average bacterial index (BI) and logarithmic
index of bacilli in biopsy (LIB). The effects of minocycline on viability
by mouse foot pad inoculation and palmitic acid oxidation assays were noted
beginning at 10 to 14 days of daily dosing and becoming more definite after
30 days of treatment. Both tests correlated fairly well. Doses of 200 mg
daily did not appear to be more efficient than minocycline 100 daily.
Phenolic glycolipid-I (PGL-I) antigen determinations done on some patients
during the first month remained positive and did not correlate with changes
in viability results. At the end of 6 months, after 5 months of 100 mg of
minocycline monotherapy, no viable organisms could be demonstrated by mouse
foot pad inoculation and palmitic acid oxidation assays; assays for PGL-I
antigen were all negative.(ABSTRACT TRUNCATED AT 250 WORDS) 
=========================================================================
5.) Efficacy of minocycline in single dose and at 100 mg twice daily for
lepromatous leprosy.
=========================================================================
Int J Lepr Other Mycobact Dis (United States), Dec 1994, 62(4) p568-73
AUTHOR(S): Gelber RH; Murray LP; Siu P; Tsang M; Rea TH
AUTHOR'S ADDRESS: San Francisco Regional Hansen's Disease Program, CA 94115.
PUBLICATION TYPE: CLINICAL TRIAL; JOURNAL ARTICLE
ABSTRACT: A clinical trial of minocycline in a total of 10 patients with
previously untreated lepromatous leprosy was conducted in order to evaluate
the efficacy of a single, initial, 200-mg dose and 100 mg twice daily of
minocycline for a total duration of up to 3 months. Patients improved
remarkably quickly. Although single-dose therapy did not result in a
significant killing of Mycobacterium leprae, viable M. leprae were cleared
from the dermis regularly by 3 months of twice-daily therapy, a rate
similar to that achieved by minocycline 100 mg once daily. Because more
side effects were noted herein than previously with 100 mg daily, we
recommend that minocycline, when applied, be administered at 100 mg daily
to leprosy patients. 
=========================================================================
6.) Field trial on efficacy of supervised monthly dose of 600 mg rifampin,
400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first
results.
=========================================================================
Author
Mane I; Cartel JL; Grosset JH
Address
Institut de Leprologie Appliquee, Dakar CD Annexe, Senegal.
Source
Int J Lepr Other Mycobact Dis, 65(2):224-9 1997 Jun
Abstract
In 1995, a field trial was implemented in Senegal in order to evaluate the
efficacy of a regimen based on the monthly supervised intake of rifampin
600 mg, ofloxacin 400 mg and minocycline 100 mg to treat leprosy. During
the first year of the trial, 220 patients with active leprosy (newly
detected or relapsing after dapsone monotherapy) were recruited: 102
paucibacillary (PB) (60 males and 42 females) and 118 multibacillary (MB)
(71 males and 47 females). All of them accepted the new treatment (none
requested to be preferably put under standard WHO/MDT), no clinical sign
which could be considered as a toxic effect of the drug was noted, and none
of the patients refused to continue treatment because of any clinical
trouble. The compliance was excellent: the 113 patients (PB and MB)
detected during the first 6 months of the trial have taken six monthly
doses in 6 months, as planned. The rate of clearance and the progressive
decrease of cutaneous lesions was satisfactory. Although it is too soon to
give comprehensive results, it should be noted that no treatment failure
was observed in the 56 PB patients who have completed treatment and have
been followed up for 6 months. The long-term efficacy of the new regimen is
to be evaluated on the rate of relapse during the years following the
cessation of treatment. If that relapse rate is acceptable (similar to that
observed in patients after treatment with current standard WHO/ MDT), the
new regimen could be a solution to treat, for instance, patients very
irregular and/or living in remote or inaccessible areas since no selection
of rifampin-resistant Mycobacterium leprae should be possible (a monthly
dose of ofloxacin and minocycline being as effective as a dose of dapsone
and clofazimine taken daily for 1 month). Nevertheless, until longer term
results of this and other trials become available, there is no
justification for any change in the treatment strategy, and all leprosy
patients should be put under standard WHO/MDT. 
=========================================================================
7.) Bactericidal activity of a single-dose combination of ofloxacin plus
minocycline, with or without rifampin, against Mycobacterium leprae in mice
and in lepromatous patients.
=========================================================================
Author
Ji B; Sow S; Perani E; Lienhardt C; Diderot V; Grosset J
Address
Facult´e de M´edecine Piti´e-Salp^etri`ere, Paris, France.
bacterio@biomath.jussieu.fr
Source
Antimicrob Agents Chemother, 42(5):1115-20 1998 May
Abstract
To develop a fully supervisable, monthly administered regimen for treatment
of leprosy, the bactericidal effect of a single-dose combination of
ofloxacin (OFLO) and minocycline (MINO), with or without rifampin (RMP),
against Mycobacterium leprae was studied in the mouse footpad system and in
previously untreated lepromatous leprosy patients. Bactericidal activity
was measured by the proportional bactericidal method. In mouse experiments,
the activity of a single dose of the combination OFLO-MINO was dosage
related; the higher dosage of the combination displayed bactericidal
activity which was significantly inferior to that of a single dose of RMP,
whereas the lower dosage did not exhibit a bactericidal effect. In the
clinical trial, 20 patients with previously untreated lepromatous leprosy
were treated with a single dose consisting of either 600 mg of RMP plus 400
mg of OFLO and 100 mg of MINO or 400 mg of OFLO plus 100 mg of MINO. The
OFLO-MINO combination exhibited definite bactericidal activity in 7 of 10
patients but was less bactericidal than the RMP-OFLO-MINO combination. Both
combinations were well tolerated. Because of these promising results, a
test of the efficacy of multiple doses of ROM in a larger clinical trial
appears justified. 
=========================================================================
8.) Efficacy of single dose multidrug therapy for the treatment of
single-lesion paucibacillary leprosy. Single-lesion Multicentre Trial Group.
=========================================================================
Source
Indian J Lepr, 69(2):121-9 1997 Apr-Jun
Abstract
A multicentre double-blind controlled clinical trial was carried out to
compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin
400 mg plus minocycline 100 mg (ROM) administered as single dose with that
of the standard six-month WHO/MDT/PB regimen. The subjects included 1483
cases with one skin lesion who were previously untreated, were
smear-negative, and had no evidence of peripheral nerve trunk involvement,
and they were randomly divided into study and control groups. The total
duration of the study from the day of intake was 18 months, and 1381
patients completed study. Only 12 patients were categorized as treatment
failure and no difference was observed between the two regimens. Occurrence
of mild side-effects and leprosy reactions were minimal (less than 1%) in
both groups. This study showed that ROM is almost as effective as the
standard WHO/MDT/PB in the treatment of single lesion PB leprosy. 
=========================================================================
9.) Bactericidal activity of single dose of clarithromycin plus
minocycline, with or without ofloxacin, against Mycobacterium leprae in
patients.
=========================================================================
Author
Ji B; Jamet P; Perani EG; Sow S; Lienhardt C; Petinon C; Grosset JH
Address
Facult´e de M´edecine Piti´e-Salp^etri`ere, Paris, France.
Source
Antimicrob Agents Chemother, 40(9):2137-41 1996 Sep
Abstract
Fifty patients with newly diagnosed lepromatous leprosy were allocated
randomly to one of five groups and treated with either a month-long
standard regimen of multidrug therapy (MDT) for multibacillary leprosy, a
single dose of 600 mg of rifampin, a month-long regimen with the dapsone
(DDS) and clofazimine (CLO) components of the standard MDT, or a single
dose of 2,000 mg of clarithromycin (CLARI) plus 200 mg of minocycline
(MINO), with or without the addition of 800 mg of ofloxacin (OFLO). At the
end of 1 month, clinical improvement accompanied by significant decreases
of morphological indexes in skin smears was observed in about half of the
patients of each group. A significant bactericidal effect was demonstrated
in the great majority of patients in all five groups by inoculating the
footpads of mice with organisms recovered from biopsy samples obtained
before and after treatment. Rifampin proved to be a bactericidal drug
against Mycobacterium leprae more potent than any combination of the other
drugs. A single dose of CLARI-MINO, with or without OFLO, displayed a
degree of bactericidal activity similar to that of a regimen daily of doses
of DDS-CLO for 1 month, suggesting that it may be possible to replace the
DDS and CLO components of the MDT with a monthly dose of CLARI-MINO, with
or without OFLO. However, gastrointestinal adverse events were quite
frequent among patients treated with CLARI-MINO, with or without OFLO, and
may be attributed to the higher dosage of CLARI or MINO or to the
combination of CLARI-MINO plus OFLO. In future trials, therefore, we
propose to reduce the dosages of the drugs to 1,000 mg of CLARI, 100 mg of
MINO, and 400 mg of OFLO. 
=========================================================================
10.) WHO Expert Committee on Leprosy.
=========================================================================
Source: World Health Organ Tech Rep Ser, 874():1-43 1998
Abstract
Considerable progress has been made in the fight against leprosy during the
past 10-15 years, following the introduction of multidrug therapy (MDT)
regimens and the establishment of the goal of eliminating leprosy as a
public health problem by the year 2000. Current estimates indicate that
there are about 1.15 million cases of leprosy in the world, compared with
10-12 million cases in the mid-1980s. This report presents the conclusions
of a WHO Expert Committee convened to review the global leprosy situation
and the technology available for eliminating the disease, to identify the
remaining obstacles to reaching the goal of eliminating leprosy as a public
health problem, and to make appropriate recommendations for the future on
technical and operational matters. The current status of leprosy
elimination is discussed, and the various antileprosy drugs are reviewed,
including the most recently available drugs. On the basis of field trials
and clinical studies, the Committee concludes that a single dose of a
combination of rifampicin, ofloxacin and minocycline is an acceptable and
cost-effective alternative regimen for the treatment of single-lesion
paucibacillary leprosy, and that the duration of the current MDT regimen
for multibacillary leprosy could possibly be shortened to 12 months. The
Committee points out the need for improved management of reactions and
neuritis and prevention of leprosy-related disabilities and impairments,
and recommends that antileprosy activities should become an integral part
of general health services and should involve communities to the fullest
extent possible. 
=========================================================================
11.) Experimental evaluation of possible new short-term drug regimens for
treatment of multibacillary leprosy.
=========================================================================
Author
Banerjee DK; McDermott-Lancaster RD; McKenzie S
Address
Department of Medical Microbiology, St George's Hospital Medical School,
London, United Kingdom. banerjee@sghms.ac.uk.
Source
Antimicrob Agents Chemother, 41(2):326-30 1997 Feb
Abstract
Groups of nude mice, with both hind footpads infected with 10(8)
Mycobacterium leprae organisms, were treated with 4-week courses of
different drug combinations. The effect treatment on each group was
evaluated by subinoculating footpad homogenates from the treated mice into
groups of normal and nude mice for subsequent regrowth, assessed 1 year
later. A combination of rifampin (RMP) with clarithromycin (CLARI),
minocycline (MINO), and ofloxacin (OFLO) resulted in the complete killing
of M. leprae after 3 weeks of treatment. A combination of sparfloxacin
(SPAR) and RMP also resulted in a similar bactericidal effect after 3 weeks
of treatment. Other drug combinations showed variable effects. Very little
or no effect was observed with any regimen if the treatment was given for
less than 2 weeks. World Health Organization (WHO) multidrug therapy (MDT)
given for 8 weeks was as effective as the two combinations described above.
The results suggest that multidrug combinations consisting of RMP-OFLO (or
SPAR)-CLARI (and/or MINO) are as effective as the WHO MDT for the treatment
of experimental leprosy. Moreover, they imply that these combinations,
which were found to be active in a 4-week experimental treatment protocol,
could be administered as treatment to patients for a period of time shorter
than the present 2-year regimen without a loss of effectiveness. 
=========================================================================
12.) Powerful bactericidal activities of clarithromycin and minocycline
against Mycobacterium leprae in lepromatous leprosy.
=========================================================================
ARTICLE SOURCE: J Infect Dis (United States), Jul 1993, 168(1) p188-90
AUTHOR(S): Ji B; Jamet P; Perani EG; Bobin P; Grosset JH
AUTHOR'S ADDRESS: Faculte de Medecine Pitie-Salpetriere, Paris, France.
PUBLICATION TYPE: CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED
TRIAL
ABSTRACT: Thirty-six patients with newly diagnosed lepromatous leprosy
were allocated randomly to three groups and treated for 56 days with
minocycline (100 mg daily), clarithromycin (500 mg daily), or
clarithromycin (500 mg) plus minocycline (100 mg daily). All groups had
rapid and remarkable clinical improvement and significant decline of the
bacterial and morphologic indices in skin smears during treatment. More
than 99% and 99.9% of the viable Mycobacterium leprae had been killed by 28
and 56 days of treatment, respectively, as measured by inoculation of
organisms recovered from skin samples, taken before and during treatment,
into the footpads of immunocompetent and nude mice. Clinical improvement
and bactericidal activity did not differ significantly among the three
groups. Adverse reactions were rare and mild, and no laboratory abnormality
was detected during the trial. Both clarithromycin and minocycline
displayed powerful bactericidal activities against M. leprae in leprosy
patients and may be considered important components of new multidrug
regimens for the treatment of multibacillary leprosy. 
=========================================================================
13.) Minocycline is a useful adjuvant therapy for pemphigus.
=========================================================================
Author
Gaspar ZS; Walkden V; Wojnarowska F
Address
Department of Dermatology, Churchill, Oxford Radcliffe Hospital,
Headington, UK.
Source
Australas J Dermatol, 37(2):93-5 1996 May
Abstract
Pemphigus is an autoimmune blistering disease with high mortality if
untreated. The cases of 10 patients who had minocycline 100 mg daily added
as adjuvant therapy are reported. Prior to the use of minocycline, all
patients had active disease, nine were on prednisolone (10-40 mg) and five
were on azathioprine (100-200 mg). The response was assessed on clinical
improvement and reduction of immunosuppressive (IS) drugs. It was graded
into four categories: major, minor, equivocal and no significant response.
A major response was seen in four patients, minor in two, equivocal in one
and no improvement in three patients. The prednisolone dose in the six
responders was reduced to 0-6 mg (0 mg in three patients), with an average
decrease of 21 mg. The average time to respond was 8 months. Of the six
responders, three were on azathioprine, which was ceased in two patients
and reduced by two-thirds in the other patient. No patient ceased
minocycline because of side effects. In conclusion, minocycline 100 mg
daily is a simple, safe and well tolerated treatment that should be tried
in patients with pemphigus to reduce disease activity and/or the dose of
potent IS agents. 
=========================================================================
14.) Confluent and reticulated papillomatosis: response to minocycline.
=========================================================================
Author
Montemarano AD; Hengge M; Sau P; Welch M
Address
Department of Dermatology, Walter Reed Army Medical Center, Washington, DC
20307, USA.
Source
J Am Acad Dermatol, 34(2 Pt 1):253-6 1996 Feb
Abstract
BACKGROUND: Confluent and reticulated papillomatosis (CRP) of Gougerot and
Carteaud is an uncommon disorder of unknown cause for which a variety of
treatments have been proposed. OBJECTIVE: We attempted to evaluate the
effectiveness of oral minocycline. METHODS: Nine patients with CRP were
treated with oral minocycline, 50 mg twice a day, for 6 weeks. The average
follow-up period was 11 months. Recurrence rate, side effects, and
effectiveness of therapy were assessed. RESULTS: All patients except two
had a 90% to 100% response to therapy. Recurrences were noted in three
patients, all of whom responded to re-treatment with minocycline. None of
the nine patients had an adverse reaction. CONCLUSION: Minocycline, 50 mg
twice a day, is safe and effective for CRP. 
=========================================================================
15.) Minocycline treatment for confluent and reticulated papillomatosis.
=========================================================================
Author
Chang SN; Kim SC; Lee SH; Lee WS
Address
Department of Dermatology, Yonsei University College of Medicine, Seoul,
Korea.
Source
Cutis, 57(6):454-7 1996 Jun
Abstract
We report six cases of confluent and reticulated papillomatosis in which
the skin lesions cleared almost completely after treatment with
minocycline. Patients with confluent and reticulated papillomatosis often
do not respond well to a variety of therapeutic agents. The response of
confluent and reticulated papillomatosis to minocycline was first described
in 1965. Although the pharmacologic mechanisms of minocycline in confluent
and reticulated papillomatosis are unknown, we suggest that it should be
considered as a first-choice therapeutic agent because of its marked
effectiveness. 
=========================================================================
16.) No detection of Borrelia burgdorferi-specific DNA in erythema migrans
lesions after minocycline treatment.
=========================================================================
ARTICLE SOURCE: Arch Dermatol (United States), Jun 1995, 131(6) p678-82
AUTHOR(S): Muellegger RR; Zoechling N; Soyer HP; Hoedl S; Wienecke R;
Volkenandt M; Kerl H
AUTHOR'S ADDRESS: Department of Dermatology, Karl-Franzens University,
Graz, Austria.
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: BACKGROUND AND DESIGN: Early treatment of erythema migrans is
important to prevent late complications. Minocycline possesses several
attributes, making it potentially useful in the treatment of borrelial
infections. In our study, minocycline was administered to 14 patients with
erythema migrans. Punch biopsy specimens were obtained from the (affected)
skin of all patients before and after therapy. The formalin-fixed,
paraffin-embedded specimens were analyzed by polymerase chain reaction for
the presence of Borrelia burgdorferi-specific DNA. RESULTS: Polymerase
chain reaction assay succeeded in amplifying B burgdorferi-specific DNA
from the first biopsy specimen, obtained from the border of erythema
migrans before initiating treatment, in eight (57%) of 14 patients. At the
end of minocycline therapy, however, polymerase chain reaction analysis
disclosed no B burgdorferi-specific DNA in any of the 14 patients. The good
clinical response of our patients with erythema migrans substantiates our
molecular findings. CONCLUSIONS: The presented polymerase chain reaction
data, together with the clinical outcome, indicate that minocycline may be
useful for treatment of early Lyme borreliosis. 
=========================================================================
17.) Minimizing cicatricial pemphigoid orodynia with minocycline.
=========================================================================
ARTICLE SOURCE: Br J Dermatol (England), May 1995, 132(5) p784-9
AUTHOR(S): Poskitt L; Wojnarowska F
AUTHOR'S ADDRESS: Dermatology Department, Amersham General Hospital,
Bucks, U.K.
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Cicatricial pemphigoid is a rare autoimmune blistering disease
of the elderly. It predominantly affects the mucosae, causing pain and
scarring. the target antigen is within the lamina lucida of the basement
membrane zone. Potential complications of systemic steroid and other
immunosuppressive therapy have prompted trials of other means of treatment.
We describe a series of seven patients treated with minocycline, six of
whom derived sustained alleviation of orodynia. Four patients developed
hyperpigmentation, and two complained of gastrointestinal discomfort which
necessitated cessation of minocycline. Complete steroid withdrawal was
achieved in two cases. Neither the disease progression nor the response to
treatment was influenced by the immunoglobulin isotype or titre. The role
of minocycline as a useful adjunct to therapy is discussed. 
=========================================================================
18.) Response of atypical bullous pyoderma gangrenosum to oral minocycline
hydrochloride and topical steroids.
=========================================================================
ARTICLE SOURCE: Acta Derm Venereol (Sweden), 1990, 70(6) p538-9
AUTHOR(S): Reynolds NJ; Peachey RD
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: An 80-year-old Caucasian female with rheumatoid arthritis and
recurrent atypical bullous pyoderma gangrenosum is described. There was no
evidence of any underlying myeloproliferative disorder. Rapid healing
occurred in response to oral minocycline hydrochloride and topical
clobetasol propionate. 
=========================================================================
19.) Blastomycosis-like pyoderma--report of a case responsive to
combination therapy utilizing minocycline and carbon dioxide laser
debridement.
=========================================================================
ARTICLE SOURCE: J Dermatol Surg Oncol (United States), Oct 1986, 12(10)
p1041-4
AUTHOR(S): Sawchuk WS; Heald PW
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Blastomycosis-like pyoderma is an uncommon reaction pattern to a
superficial bacterial infection in persons with a variety of predisposing
conditions such as chronic ethanol use and poor nutrition. We are reporting
a case that initially responded poorly to previously described treatment
regimens but responded well to combination treatment with carbon dioxide
laser debridement and long-term minocycline. 
=========================================================================
20.) A sporotrichoid-like Mycobacterium kansasii infection of the skin
treated with minocycline hydrochloride.
=========================================================================
ARTICLE SOURCE: Br J Dermatol (England), Jul 1979, 101(1) p75-9
AUTHOR(S): Dore N; Collins JP; Mankiewicz E
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: A sporotrichoid-like Mycobacterium kansasii infection of the
skin is reported. This is the fifth reported case in the English literature
of dermatological manifestations of a M. kansasii infection and the first
reported case of a response to minocycline hydrochloride therapy. 
=========================================================================
21.) Primary lymphocutaneous nocardiosis due to Nocardia otitidiscaviarum:
the first case report from Japan.
=========================================================================
ARTICLE SOURCE: J Dermatol (Japan), May 1995, 22(5) p344-7
AUTHOR(S): Suzuki Y; Toyama K; Utsugi K; Yazawa K; Mikami Y; Fujita M;
Shinkai H
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: We report a case of lymphocutaneous syndrome caused by Nocardia
otitidiscaviarum (formerly known as N. caviae) in a 78-year-old woman who
underwent long-term therapy with prednisolone for bronchial asthma.
Histological examination showed granulomatous reaction with multiple
polymorphonuclear leukocytes and revealed a Gram positive filament in the
dermis. Gram-positive, slightly acid-fast branched filaments were also
found in the smear of the purulent material. The cell wall constituents of
the isolate were meso-diaminopimelic acid, arabinose, and galactose; the
mycolic acid pattern of the isolate was Nocardia type. The organism
decomposed xanthine and hypoxanthine, but not tyrosine or casein, which
distinguished it from N. asteroides and N. brasiliensis. The skin lesions
responded to minocycline and later to a combination of doxycycline and
ofloxacin. This primary lymphocutaneous nocardiosis due to N.
otitidiseaviarum is the first in Japan. 
=========================================================================
22.) Minocycline treatment of pulmonary nocardiosis.
=========================================================================
ARTICLE SOURCE: JAMA (United States), Aug 19 1983, 250(7) p930-2
AUTHOR(S): Petersen EA; Nash ML; Mammana RB; Copeland JG
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Minocycline hydrochloride was used to treat pulmonary infections
with Nocardia asteroides in five cardiac allograft recipients. In three
patients, minocycline was successfully used as the only antinocardial
agent. Two other patients were found to have leukopenia after initial
therapy with sulfisoxazole. These two patients were subsequently treated
with minocycline. The clinical success with minocycline in these highly
immunosuppressed patients suggests that minocycline is an effective
antinocardial agent. These data did not allow any conclusion regarding
which drug, minocycline or sulfisoxazole, is superior in the treatment of
this disease. 
=========================================================================
23.) Minocycline in rheumatoid arthritis. A 48-week, double-blind,
placebo-controlled trial. MIRA Trial Group [see comments]
=========================================================================
Author
Tilley BC; Alarc´on GS; Heyse SP; Trentham DE; Neuner R; Kaplan DA; Clegg
DO; Leisen JC; Buckley L; Cooper SM; et al
Address
Henry Ford Health Sciences Center, Detroit, Michigan.
Source
Ann Intern Med, 122(2):81-9 1995 Jan 15
Abstract
OBJECTIVE: To assess the safety and efficacy of minocycline in the
treatment of rheumatoid arthritis. DESIGN: A double-blind, randomized,
multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo.
SETTING: 6 clinical centers in the United States. PATIENTS: 219 adults with
active rheumatoid arthritis who had previous limited treatment with
disease-modifying drugs. MEASUREMENTS: As the primary outcomes, 60
diarthrodial joints were examined for tenderness, and 58 joints were
examined for swelling (hips excluded). Grip strength, evaluator's global
assessment, morning stiffness, Modified Health Assessment Questionnaire,
patient's global assessment, hematocrit, erythrocyte sedimentation rate,
platelet count, and IgM rheumatoid factor levels were also assessed;
radiographs of both hands and wrists were taken. RESULTS: 109 and 110
patients were randomly assigned to receive minocycline and placebo,
respectively. At entry, demographic, clinical, and laboratory measurements
were similar in both groups. Most patients had mild to moderate disease
activity and some evidence of destructive disease. At the week 48 visit,
79% of the minocycline group and 78% of the placebo group continued to
receive the study medication. At 48 weeks, more patients in the minocycline
group than in the placebo group showed improvement in joint swelling (54%
and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both
comparisons). The minocycline group also showed greater improvement in
hematocrit, erythrocyte sedimentation rate, platelet count, and IgM
rheumatoid factor levels (all P values < 0.001), and more patients
receiving minocycline had laboratory values within normal ranges at 48
weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all
greater than the critical value of 0.005 (Bonferroni adjustment for
multiple comparisons). The frequency of reported side effects was similar
in both groups, and no serious toxicity occurred. CONCLUSIONS: Minocycline
was safe and effective for patients with mild to moderate rheumatoid
arthritis. Its mechanisms of action remain to be determined. 
=========================================================================
24.) Minocycline prevents the decrease in bone mineral density and
trabecular bone in ovariectomized aged rats.
=========================================================================
Author
Williams S; Wakisaka A; Zeng QQ; Barnes J; Martin G; Wechter WJ; Liang CT
Address
Gerontology Research Center, National Institute of Aging, National
Institutes of Health, Baltimore, MD 21224, USA.
Source
Bone, 19(6):637-44 1996 Dec
Abstract
In the current study, we examined the effects of minocycline, on the
osteopenia of ovariectomized aged rats. Old female rats were randomly
divided into five groups: sham, ovariectomized control and ovariectomized
treated with minocycline, 17beta-estradiol, or both agents. Bone samples
were collected 8 wk after the treatment. Ovariectomy reduced bone mineral
density of the whole femur and at the condylar, distal metaphyseal and
head-neck-trochanter regions 10%-19% and the loss of bone density was
prevented by treatment with minocycline or 17beta-estradiol.
Histomorphometric analysis of distal femur showed ovariectomy reduced the
trabecular bone area, the trabecular bone number, trabecular bone thickness
and increased the trabecular bone separation. The microanatomic structure
of trabecular bone also showed that the number of nodes, node to node,
cortical to node, node to free end was reduced by ovariectomy. Treatment
with minocycline attenuated the effect of ovariectomy on trabecular bone in
aged animals. In contrast, cortical bone was not affected by ovariectomy or
minocycline treatment. The effect of minocycline on bone turnover was also
examined. Minocycline increased osteoid surface, mineralizing surface,
mineral apposition rate, bone formation rate and reduced eroded surface. We
have therefore concluded that the modest increase in bone mineral density
and the improvement in the trabecular bone status noted in minocycline
treated ovariectomized aged rats is likely due to an increase in bone
formation coupled with a decrease in bone resorption. 
=========================================================================
25.) Minocycline and cefotaxime in the treatment of experimental murine
Vibrio vulnificus infection.
=========================================================================
Author
Chuang YC; Ko WC; Wang ST; Liu JW; Kuo CF; Wu JJ; Huang KY
Address
Department of Internal Medicine, National Cheng Kung University Hospital,
Tainan, Taiwan.
Source
Antimicrob Agents Chemother, 42(6):1319-22 1998 Jun
Abstract
We conducted an in vivo study with the mouse model of Vibrio vulnificus
infection to evaluate the efficacies of therapy with minocycline or
cefotaxime alone and in combination. V. vulnificus was introduced
subcutaneously into the area over the right thigh. The inoculum size ranged
from 1.0 x 10(3) to 1.2 x 10(8) CFU from experiment to experiment but was
constant for all animals in the same experiment. Antibiotics were given
intraperitoneally 2 h after the bacteria were inoculated. In experiments 1
to 4, the standard dose for humans was used to treat the infection, while
in experiment 5, five times the standard dose for humans was used to treat
the infection. In experiment 1, with a small inoculum of 5 x 10(3) CFU, all
mice in the saline-treated control group and the cefotaxime-, minocycline-,
and combined antibiotic-treated groups survived. In experiment 2, with a
moderate inoculum of 1.2 x 10(5) CFU, all the mice in the three
antibiotic-treated groups survived, while only two of nine mice in the
control group survived. In experiment 3, with a large inoculum of 8.0 x
10(7) CFU, six of nine mice in the combined antibiotic-treated group
survived, while only one of nine mice in the cefotaxime-treated group and
none of the mice in the control and minocycline-treated groups survived. In
experiment 4, with a large inoculum of 1.2 x 10(8) CFU, 8 of 20 mice in the
combined antibiotic-treated group survived, while none of the 20 mice in
the control group, the group treated with cefotaxime alone, and the group
treated with minocycline alone survived. In experiment 5, in which mice
were infected with a large inoculum of 6.6 x 10(7) CFU and treated with
five times the standard human dose of antibiotics, 10 of 12 mice in the
combined antibiotic-treated group survived, while only 4 of 12 mice in the
minocycline-treated group, 1 of 12 mice in the cefotaxime-treated group,
and none of the mice in the control group survived. In experiments 3 to 5,
the difference in the survival rates between the combined
antibiotic-treated and minocycline-treated groups was statistically
significant (P < 0.05). These results indicate that combination therapy
with cefotaxime and minocycline is distinctly more advantageous than
therapy with the single antibiotic regimen for the treatment of severe
experimental V. vulnificus infections. 
=========================================================================
26.) The role of minocycline in the treatment of intracranial 9L glioma.
=========================================================================
Author
Weingart JD; Sipos EP; Brem H
Address
Department of Neurological Surgery, Johns Hopkins University School of
Medicine, Baltimore, Maryland.
Source
J Neurosurg, 82(4):635-40 1995 Apr
Abstract
This study was designed to explore the question of whether minocycline, a
semisynthetic tetracycline shown to inhibit tumor-induced angiogenesis,
could control the growth of the rat intracranial 9L gliosarcoma.
Minocycline was tested alone and in combination with
1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in vivo. Treatment was started
at the time of intracranial implantation of 9L gliosarcoma into male
Fischer 344 rats, 5 days later, or after tumor resection. Minocycline was
delivered locally with a controlled-release polymer or systemically by
intraperitoneal injection. Systemic minocycline did not extend survival
time. Local treatment with minocycline by a controlled-release polymer
implanted at the time of tumor implantation extended median survival time
by 530% (p < 0.001) compared to treatment with empty polymer. When
treatment was begun 5 days after tumor implantation, minocycline delivered
locally or systemically had no effect on survival. However, after tumor
resection, treatment with locally delivered minocycline resulted in a 43%
increase in median survival time (p < 0.002) compared to treatment with
empty polymer. Treatment with a combination of minocycline delivered
locally in a controlled-release polymer and systemic BCNU 5 days after
tumor implantation resulted in a 93% extension of median survival time
compared to BCNU alone (p < 0.002). In contrast, treatment with a
combination of systemic minocycline and BCNU did not increase survival time
compared to systemic BCNU alone. These results demonstrate that minocycline
affects tumor growth when delivered locally and suggest that minocycline
may be a clinically effective modulator of intracranial tumor growth when
used in combination with a chemotherapeutic agent and surgical resection. 
=========================================================================
27.) Evaluation of the long-term efficacy and safety of locally-applied
minocycline in adult periodontitis patients.
=========================================================================
Author
Timmerman MF; van der Weijden GA; van Steenbergen TJ; Mantel MS; de Graaff
J; van der Velden U
Address
Department of Periodontology, Academic Centre for Dentistry, Amsterdam, The
Netherlands.
Source
J Clin Periodontol, 23(8):707-16 1996 Aug
Abstract
The objectives of the present study were to establish in a long-term
investigation the safety as well as the clinical and microbiological
efficacy of scaling and rootplaning combined with local application of 2%
minocycline hydrochloride-gel versus placebo-gel in patients with moderate
to severe chronic adult periodontitis. This was an 18 months, randomized,
double-blind, parallel, comparative study, in which 20 healthy patients
with moderate to severe chronic periodontitis participated. At baseline,
all patients received professional oral hygiene-instruction and supra- and
subgingival scaling and root planing. The minocycline-gel was applied
subgingivally baseline, 2 weeks, 1, 3, 6, 9 and 12 months. Microbiological
evaluation was carried out using DMDx to identify the following bacteria:
Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus
actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum and
Treponema denticola. In addition standard microbiological techniques were
used for the detection of P. gingivalis, P. intermedia, P. micros, A.
actinomycetemcomitans, C. rectus, F. nucleatum, C. albicans and
Enterobacteriaceae. Results showed a statistically significant improvement
for all clinical parameters irrespective of the treatment modality. No
differences were observed between test and control with regard to probing
depth and attachment level. The DMDx data showed a significant reduction in
both the numbers and the prevalence over the 15 months period, but no
significant difference between groups. Culture data showed that at baseline
two-third were positive for P. gingivalis and P. intermedia. Analysis over
the 18 month period showed no significant difference between the two
treatment modalities. C. albicans and Enterobacteriaceae were detected only
in small proportions at each time interval in a limited number of patients.
No adverse reactions were observed during the trial period. The present
patient group responded favourably to scaling and rootplaning, but did not
benefit from an effect of local of minocycline. Subgingival debridement in
combination with oral hygiene instruction by itself has been shown to be
effective. It remains to be studied whether local application of
minocycline can be effective as an adjunct to mechanical therapy in sites
that respond poorly to conventional treatment. 
=========================================================================
28.) Clinical and microbiological effects of minocycline-loaded
microcapsules in adult periodontitis.
=========================================================================
Author
Yeom HR; Park YJ; Lee SJ; Rhyu IC; Chung CP; Nisengard RJ
Address
Department of Periodontology, College of Dentistry, Seoul National
University, Korea.
Source
J Periodontol, 68(11):1102-9 1997 Nov
Abstract
Clinical and microbiological effects of subgingival delivery of 10%
minocycline-loaded (MC), bioabsorbable microcapsules were examined in 15
adult periodontitis patients. Patients received oral hygiene instruction 2
weeks prior to the study. At baseline (day 0) all teeth received
supragingival scaling (SC); 2 quadrants received no further treatment and 1
quadrant received subgingival scaling and root planning (SRP). In the
fourth quadrant, the tooth with the deepest probing sites (at least 1 site
> or = 5 mm) was treated with minocycline microcapsules. The sites were
evaluated at baseline and weeks 1, 2, 4, and 6. Clinical indices included
bleeding on probing (BOP), probing depths (PD), and attachment loss (AL).
Microbiological evaluations included percent morphotypes by phase-contrast
microscopy; cultivable anaerobic, aerobic, and black-pigmented Bacteroides
(BPB); and percent Porphyromonas gingivalis, Prevotella intermedia,
Eikenella corrodens, and Actinomyces viscosus by indirect
immunofluorescence. In the SC + MC group, BOP, PD, and AL were
significantly reduced from baseline for weeks 1 to 6. BOP in the SC + MC
group was significantly reduced compared to the SRP group from weeks 2 to
6. In the SC + MC group the percent of spirochetes and motile rods
decreased and the percent of cocci increased after 1 week. The increased
cocci and decreased motile rods were statistically greater at weeks 4 and 6
in the SC + MC group compared to the SRP group. This study demonstrates
that local subgingival delivery of 10% minocycline-loaded microcapsules as
an adjunct to scaling results in reduction in the percent sites bleeding on
probing greater than scaling and root planning alone and induces a
microbial response more favorable for periodontal health than scaling and
root planing. 
=========================================================================
29.) The broad-spectrum activity and efficacy of catheters coated with
minocycline and rifampin.
=========================================================================
Author
Raad I; Darouiche R; Hachem R; Mansouri M; Bodey GP
Address
Section of Infectious Diseases, University of Texas M. D. Anderson Cancer
Center, Houston 77030, USA.
Source
J Infect Dis, 173(2):418-24 1996 Feb
Abstract
The in vitro and in vivo activities of catheters coated with minocycline
and rifampin and with chlorhexidine gluconate and silver sulfadiazine were
evaluated. When incubated in serum at 37 degrees C, the half-life of the
inhibitory activity of catheters coated with minocycline and rifampin was
25 days compared with 3 days for catheters coated with chlorhexidine
gluconate and silver sulfadiazine. In a rabbit model, catheters coated with
minocycline and rifampin were significantly more efficacious than catheters
coated with chlorhexidine and silver sulfadiazine in preventing
colonization and infection with Staphylococcus aureus (P < .05). Catheters
coated with minocycline and rifampin demonstrated broad-spectrum in vitro
inhibitory activity against gram-positive bacteria, gram-negative bacteria,
and Candida albicans that was significantly superior to the inhibitory
activity of catheters coated with chlorhexidine gluconate and silver
sulfadiazine (P < .01). Minocycline and rifampin were also highly
efficacious in preventing colonization and infection in vivo. 
=========================================================================
30.) Symptomatic hepatic cysts: treatment with single-shot injection of
minocycline hydrochloride.
=========================================================================
Author
Cellier C; Cuenod CA; Deslandes P; Auroux J; Landi B; Siauve N; Barbier JP;
Frija G
Address
Department of Gastroenterology, Universit´e Ren´e Descartes, H^opital
Laennec, Paris, France.
Source
Radiology, 206(1):205-9 1998 Jan
Abstract
PURPOSE: To assess the efficacy of percutaneous minocycline hydrochloride
sclerotherapy in symptomatic hepatic cysts. MATERIALS AND METHODS: From
November 1992 to June 1994, seven of eight consecutive adults with large
symptomatic hepatic cysts (diameter, 55-130 mm) were treated with a single
intracystic injection of minocycline hydrochloride in an ambulatory
procedure. Five patients had a solitary cyst, and two had polycystic liver
disease. The target cyst was punctured under ultrasound guidance and local
anesthesia with a 22-gauge Chiba needle. Half of the cyst content was
aspirated before injection of 100-500 mg of minocycline hydrochloride
diluted in 5-25 mL of saline. The minocycline hydrochloride was left in the
cyst at the end of the procedure. RESULTS: After a mean follow-up of 28
months (range, 24-42 months), all five patients with solitary cysts were
asymptomatic and four had documented complete cyst regression; the two
patients with multiple hepatic cysts showed only transient clinical
improvement. CONCLUSION: Single-shot injection of minocycline hydrochloride
is an effective treatment for symptomatic solitary hepatic cysts but is
less effective in polycystic liver disease. 
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31.) Systematic review and meta-analysis of the efficacy and safety of minocycline in schizophrenia.
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CNS Spectr. 2017 Feb 9:1-12. doi: 10.1017/S1092852916000638. [Epub ahead of print]
Solmi M1, Veronese N2, Thapa N3, Facchini S4, Stubbs B5, Fornaro M6, Carvalho AF7, Correll CU8.
Author information
11Department of Neurosciences,University of Padova,Padova,Italy.
23Institute for Clinical Research and Education in Medicine (IREM),Padova,Italy.
35Kaski Sewa Hospital and Research Centre,Pokhara,Nepal.
44Department of Medicine (DIMED), Geriatrics Section,University of Padova,Padova,Italy.
56Physiotherapy Department,South London and Maudsley NHS Foundation Trust,London,United Kingdom.
68New York Psychiatric Institute,Columbia University,New York,New York,USA.
79Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine,Federal University of Ceará,Fortaleza,Ceará,Brazil.
810The Zucker Hillside Hospital,Psychiatry Research,Northwell Health,Glen Oaks,New York,USA.
Abstract
OBJECTIVE:
Our aim was to perform an updated systematic review and meta-analysis on the efficacy and safety of adjunctive minocycline as a treatment of schizophrenia.
METHODS:
We conducted a PubMed/Scopus database search from inception to 3 February 2016 for randomized, placebo-controlled trials (RCTs), open non-randomized studies, and case reports/series evaluating minocycline in patients with schizophrenia. Random-effects meta-analysis of positive, negative, depressive, and cognitive symptom rating scales, discontinuation and adverse effects rates calculating standardized mean difference (SMD), and risk ratios±95% confidence intervals (CI 95%) were calculated.
RESULTS:
Six RCTs were eligible (minocycline n=215, placebo n=198) that demonstrated minocycline's superiority versus placebo for reducing endpoint Positive and Negative Syndrome Scale (PANSS) total scores (SMD=-0.59; CI 95%=[1.15, -0.03]; p=0.04), negative (SMD=-0.76; CI 95%=[-1.21, -0.31]; p=0.001); general subscale scores (SMD=-0.44; CI 95%=[-0.88, -0.00]; p=0.05), Clinical Global Impressions scores (SMD=-0.50; CI 95%=[-0.78, -0.22]; p<0.001); and executive functioning (SMD=0.22; CI 95%=[0.01, 0.44]; p=0.04). Endpoint PANSS positive symptom scores (p=0.13), depression rating scale scores (p=0.43), attention (p=0.47), memory (p=0.52), and motor speed processing (p=0.50) did not significantly differ from placebo, before execution of a trim-and-fill procedure. Minocycline did not differ compared to placebo on all-cause discontinuation (p=0.56), discontinuation due to inefficacy (p=0.99), and intolerability (p=0.51), and due to death (p=0.32). Data from one open-label study (N=22) and three case series (N=6) were consistent with the metaanalytic results.
CONCLUSIONS:
Minocycline appears to be an effective adjunctive treatment option in schizophrenia, improving multiple relevant disease dimensions. Moreover, minocycline has an acceptable safety and tolerability profile. However, more methodologically sound and larger RCTs remain necessary to confirm and extend these results.
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32.) Adjunctive minocycline for schizophrenia: A meta-analysis of randomized controlled trials.
================================================================
Eur Neuropsychopharmacol. 2017 Jan;27(1):8-18. doi: 10.1016/j.euroneuro.2016.11.012. Epub 2016 Dec 2.
Xiang YQ1, Zheng W2, Wang SB3, Yang XH4, Cai DB5, Ng CH6, Ungvari GS7, Kelly DL8, Xu WY9, Xiang YT10.
Author information
1National Clinical Research Center for Mental Disorders, Beijing, China & Center of Depression, Beijing Institute for Brain Disorders, China; Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
2The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. Electronic address: zhengwei0702@163.com.
3Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao.
4The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China.
5Faculty of Traditional Chinese Medicine, the First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
6Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia.
7The University of Notre Dame Australia/Marian Centre, Perth, Australia; School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth, Australia.
8Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
9The Affiliated Hospital of JiangXi University of Traditional Chinese Medicine, Nanchang, China.
10Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao. Electronic address: xyutly@gmail.com.
Abstract
This study aimed to conduct a meta-analysis of the efficacy and safety of adjunctive minocycline for schizophrenia. Randomized controlled trials (RCTs) comparing adjunctive minocycline with placebo in patients with schizophrenia were included in the meta-analysis. Two independent investigators extracted and synthesized data. Standard mean differences (SMDs), risk ratio (RR) ±95% confidence intervals (CIs) and the number-needed-to-harm (NNH) were calculated. Eight RCTs with 548 schizophrenia patient including 286 (52.2%) patients on minocycline (171.9±31.2mg/day) and 262 (47.8%) on placebo completed 18.5±13.4 weeks of treatment. Meta-analyses of Positive and Negative Syndrome Scale (PANSS) (7 RCTs with 8 treatment arms)/Brief Psychiatric Rating Scale (BPRS) (1 RCT) total score [SMD: -0.64, (95%CI: -1.02, -0.27), P=0.0008; I2=74%], positive, negative and general symptom scores [SMD: -0.69 to -0.22 (95%CI: -0.98, -0.03), P=0.02-0.00001; I2=7-63%] revealed a significant superiority of adjunctive minocycline treatment over the placebo. There was no significant difference regarding neurocognitive function, discontinuation rate and adverse drug reactions between the two groups. This meta-analysis showed that adjunctive minocycline appears to be efficacious and safe for schizophrenia. Due to significant heterogeneity, future studies with a large sample size are needed to confirm these findings.
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33.) Minocycline as an adjunct for treatment-resistant depressive symptoms: study protocol for a pilot randomised controlled trial.
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Trials. 2015 Sep 15;16:410. doi: 10.1186/s13063-015-0933-5.
Husain MI1, Chaudhry IB2, Rahman RR3, Hamirani MM4, Qurashi I5, Khoso AB6, Deakin JF7, Husain N8, Young AH9.
Author information
1Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK. ishrat-h@doctors.net.uk.
2The Mount, Whalley Road, Accrington, Lanacashire, BB5 5DE, UK. imran.chaudhry@manchester.ac.uk.
3Dow Institute of Health Sciences, Karachi, Pakistan. razaur@yahoo.com.
4Department of Psychiatry, Abbasi Shaheed Hospital, Karachi, Pakistan. mhamirani@gmail.com.
5Ashworth Research Centre, Mersey Care NHS Trust, Parkbourn, Maghull, L51 1HW, UK. inti.qurashi@merseycare.nhs.uk.
6Pakistan Institute of Learning and Living, Karachi, Pakistan. ameerbuxkhoso@gmail.com.
7University of Manchester, Oxford Road, Manchester, UK. bill.deakin@manchester.ac.uk.
8University of Manchester, Oxford Road, Manchester, UK. nusrat.husain@manchester.ac.uk.
9Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK. allan.young@kcl.ac.uk.
Abstract
BACKGROUND:
Depression is one of the leading causes of disability worldwide. A high proportion of patients do not respond to standard drug treatments. Recent evidence has suggested that anti-inflammatory treatment may have beneficial effects in major depression. Minocycline is a tetracycline antibiotic with good CNS penetration that exerts effects on multiple interacting symptoms implicated in the pathophysiology of mood disorders. Open-label studies have suggested that minocycline is effective as an adjunct drug in improving depressive symptoms.
METHODS/DESIGN:
This is a multi-centre, 3-month, double-blind, placebo-controlled, pilot trial of minocycline added to treatment as usual for patients suffering from DSM-IV major depressive disorder. This will be a double-blind, randomised, controlled, two parallel-arm study with 20 participants in each arm, giving a total of 40 participants. There will be a screening visit, a randomization visit and four follow-up visits. Clinical assessments using the Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ -9) and the Generalised Anxiety Disorder scale (GAD-7) will be carried out at every visit. Side effects checklists will also be undertaken at each visit. Biomarkers (inflammatory cytokines and CRP) will be measured at baseline and at the end of the treatment phase. Minocycline will be started at 100 mg once daily (OD) and will be increased to 200 mg at two weeks.
DISCUSSION:
Anti-inflammatory treatments have been shown to have some beneficial effects in the treatment of major depressive disorder. The aim of this pilot randomised controlled trial is to establish the degree of improvement in depressive symptoms with the addition of minocycline to treatment as usual.
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34.) Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2x2 clinical trial.
===============================================================
BMJ Open. 2012 Feb 22;2(1):e000643. doi: 10.1136/bmjopen-2011-000643. Print 2012.
Savitz J1, Preskorn S, Teague TK, Drevets D, Yates W, Drevets W.
Author information
1Laureate Institute for Brain Research (LIBR), Tulsa, Oklahoma, USA.
Abstract
INTRODUCTION:
New medication classes are needed to improve treatment effectiveness in the depressed phase of bipolar disorder (BD). Extant evidence suggests that BD is characterised by neural changes such as dendritic remodelling and glial and neuronal cell loss. These changes have been hypothesised to result from chronic inflammation. The principal aims of the proposed research is to evaluate the antidepressant efficacy in bipolar depression of minocycline, a drug with neuroprotective and immune-modulating properties, and of aspirin, at doses expected to selectively inhibit cyclooxygenase 1 (COX-1).
METHODS AND ANALYSIS:
120 outpatients between 18 and 55 years of age, who meet DSM-IV-TR criteria for BD (type I or II) and for a current major depressive episode will be recruited to take part in a randomised, double-blind, placebo-controlled, parallel-group, proof-of-concept clinical trial following a 2×2 design. As adjuncts to existing treatment, subjects will be randomised to receive one of the four treatment combinations: placebo-minocycline plus placebo-aspirin, active-minocycline plus placebo-aspirin, placebo-minocycline plus active-aspirin or active-minocycline plus active-aspirin. The dose of minocycline and aspirin is 100 mg twice daily and 81 mg twice daily, respectively. Antidepressant response will be evaluated by assessing changes in the Montgomery-Asberg Depression Rating Scale scores between baseline and the end of the 6-week trial. As secondary outcome measures, the anti-inflammatory effects of minocycline and aspirin will be tested by measuring pre-treatment and post-treatment levels of C reactive protein and inflammatory cytokines.
ETHICS AND DISSEMINATION:
Minocycline has been widely used as an antibiotic in doses up to 400 mg/day. Low-dose aspirin has been safely used on a worldwide scale for its role as an antithrombotic and thrombolytic. The study progress will be overseen by a Data, Safety and Monitoring Board, which will meet once every 6 months. Results of the study will be published in peer-reviewed publications.
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35.) Interferon β-secreting mesenchymal stem cells combined with minocycline attenuate experimental autoimmune encephalomyelitis.
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J Neuroimmunol. 2014 Sep 15;274(1-2):20-7. doi: 10.1016/j.jneuroim.2014.06.001. Epub 2014 Jun 20.
Hou Y1, Heon Ryu C2, Jun JA1, Kim SM2, Jeong CH1, Jeun SS3.
Author information
Author information
1Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
2Postech-Catholic Biomedical Engineering Institute, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
3Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: ssjeun@catholic.ac.kr
Abstract
We previously demonstrated that interferon β (IFN-β)-secreting mesenchymal stem cells (MSCs-IFN-β) strongly reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE), compared with MSCs alone. Recently, minocycline ameliorates the clinical severity of multiple sclerosis (MS). Herein, we evaluated the effects of a combined treatment of MSCs-IFN-β and minocycline on EAE mice. The combined treatment significantly alleviated the clinical severity mainly by maintaining the integrity of blood-spinal cord barrier, in a manner likely involving inhibition of microvascular disruption, matrix metalloproteinases, neuroinflammation, and enhancement of immunomodulatory effects. Therefore, this combined treatment has the potential to improve the functional recovery of patients with MS.
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36.) Glatiramer acetate in combination with minocycline in patients with relapsing--remitting multiple sclerosis: results of a Canadian, multicenter, double-blind, placebo-controlled trial.
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Mult Scler. 2009 Oct;15(10):1183-94. doi: 10.1177/1352458509106779. Epub 2009 Sep 23.
Metz LM1, Li D, Traboulsee A, Myles ML, Duquette P, Godin J, Constantin M, Yong VW; GA/minocycline study investigators.
Collaborators (4)
Yeung MM, Patry DG, Zabad RK, Stenerson PE.
Author information
1Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada. lmetz@ucalgary.ca
Abstract
Minocycline is proposed as an add-on therapy to improve the efficacy of glatiramer acetate in relapsing-remitting multiple sclerosis. The effect of minocycline plus glatiramer acetate was evaluated in this double-blind, placebo-controlled study by determining the total number of T1 gadolinium-enhanced lesions at months 8 and 9 in patients who were starting glatiramer acetate and had at least one T1 gadolinium-enhanced lesion on screening magnetic resonance imaging. Forty-four participants were randomized to either minocycline 100 mg twice daily or matching placebo for 9 months as add-on therapy. They were assessed at screening and months 1, 3, 6, 8 and 9. Forty participants completed the study. Compared with glatiramer acetate/placebo, glatiramer acetate/minocycline reduced the total number of T1 gadolinium-enhanced lesions by 63% (mean 1.47 versus 2.95; p = 0.08), the total number of new and enlarging T2 lesions by 65% (mean 1.84 versus 5.14; p = 0.06), and the total T2 disease burden (p = 0.10). A higher number of gadolinium-enhanced lesions were present in the glatiramer acetate/minocycline group at baseline; this was incorporated into the analysis of the primary endpoint but makes interpretation of the data more challenging. The risk of relapse tended to be lower in the combination group (0.19 versus 0.41; p = NS). Treatment was safe and well tolerated. We conclude that efficacy endpoints showed a consistent trend favoring combination treatment. As minocycline is a relatively safe oral therapy, further study of this combination is warranted in relapsing-remitting multiple sclerosis.
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37.) The Anti-Inflammatory Role of Minocycline in Alzheimer´s Disease.
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Curr Alzheimer Res. 2016;13(12):1319-1329
Budni J1, Garcez ML, de Medeiros J, Cassaro E, Bellettini-Santos T, Mina F, Quevedo J.
Author information
1Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo, Sul Catarinense, 88806-000 Criciúma, SC, Brazil. josiane.budni@unesc.net.
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder where the main risk factor is age, since its incidence increases dramatically after the age of 60. It is the most common form of dementia, and is accompanied by memory loss and cognitive impairment. Although AD was discovered over a century ago, the only drugs approved by the US Food and Drug Administration for use in its treatment are four cholinesterase inhibitors and memantine. However, these drugs are not fully effective in the treatment of AD. Therefore, the incessant search for new methods of treating AD continues, with the hope of improving both the effectiveness of therapies and the quality of life for patients suffering with AD. Current evidence suggests that the antibiotic minocycline could be a potential therapeutic drug for use in the treatment of AD due to its anti-neuroinflammatory effects. Minocycline is a tetracycline derivative that combines an anti-inflammatory property that is capable of crossing the blood brain barrier with neuroprotective properties that work by limiting inflammation and oxidative stress. Several studies have established the presence of inflammatory markers in the brains of patients suffering with AD, including elevated levels of cytokines/chemokines and microgliosis in damaged regions. Cytokines have been associated with increased tau phosphorylation and decreased levels of synaptophysin, establishing their roles in the cytoskeletal and synaptic alterations that take place in AD. Therefore, pharmacological approaches that allow for the discovery and development of new anti-inflammatory agents such as minocycline will be welcomed in the continuing struggle against AD. Considering these facts, this review will discuss the anti-inflammatory mechanisms underlying the neuroprotective effects of minocycline as a novel therapeutic approach for the treatment of AD.
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38.) Discovering new treatments for Alzheimer's disease by repurposing approved medications.
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Curr Top Med Chem. 2013;13(18):2306-27.
Appleby BS1, Cummings JL.
Author information
1Cleveland Clinic Lou Ruvo Center for Brain Health, 9500 Euclid Avenue/U10, Cleveland, OH 44195. applebyb77@gmail.com.
Abstract
Alzheimer's disease (AD) is the most common cause of dementia and a major cause of morbidity and mortality. The greatest risk factor for AD is age and as many countries are experiencing an aging population, the expected rise in AD threatens to have serious medical and socioeconomic impact in the coming decades. The only approved medications for AD are symptomatic and there are no currently available disease modifying treatments. Hence, a disease modifying treatment is desperately needed for AD not only for proper care and management of affected patients, but also to reduce society's socioeconomic burden. Developing novel compounds for any indication is a time, effort, and money consuming endeavor and most treatments never make it to market. Other research and development strategies are needed, especially for the treatment of AD. We provide a review of the current literature in assessing possibilities of repurposing medications currently used for non-AD indications. Many different compounds from many different pharmacological classes have already been studied in an AD context. We provide a "pragmatic drug repurposing score" for each of these compounds based on type of studies conducted, number of possible mechanisms of action, efficacy in AD and other neurodegenerative disease studies, tolerability profile, and their ability to cross the blood brain barrier. The current data suggest several compounds worthy of further study as treatments for AD. Compounds with the highest scores include lithium, minocycline, exenatide, valproic acid, methylene blue, and nicotine.
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39.) Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder.
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Clin Interv Aging. 2013;8:1089-95. doi: 10.2147/CIA.S46536. Epub 2013 Aug 19.
Cai Z1, Yan Y, Wang Y.
Author information
1Department of Neurology, the Lu'an Affiliated Hospital of Anhui Medical University, Lu'an People's Hospital, Lu'an, Anhui Province, People's Republic of China. c0909@hotmail.com
Abstract
BACKGROUND:
Compelling evidence has shown that diabetic metabolic disorder plays a critical role in the pathogenesis of Alzheimer's disease, including increased expression of β-amyloid protein (Aβ) and tau protein. Evidence has supported that minocycline, a tetracycline derivative, protects against neuroinflammation induced by neurodegenerative disorders or cerebral ischemia. This study has evaluated minocycline influence on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the brain of diabetic rats to clarify neuroprotection by minocycline under diabetic metabolic disorder.
METHOD:
An animal model of diabetes was established by high fat diet and intraperitoneal injection of streptozocin. In this study, we investigated the effect of minocycline on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the hippocampus of diabetic rats via immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay.
RESULTS:
These results showed that minocycline decreased expression of Aβ protein and lowered the phosphorylation of tau protein, and retarded the proinflammatory cytokines, but not amyloid precursor protein.
CONCLUSION:
On the basis of the finding that minocycline had no influence on amyloid precursor protein and beta-site amyloid precursor protein cleaving enzyme 1 which determines the speed of Aβ generation, the decreases in Aβ production and tau hyperphosphorylation by minocycline are through inhibiting neuroinflammation, which contributes to Aβ production and tau hyperphosphorylation. Minocycline may also lower the self-perpetuating cycle between neuroinflammation and the pathogenesis of tau and Aβ to act as a neuroprotector. Therefore, the ability of minocycline to modulate inflammatory reactions may be of great importance in the selection of neuroprotective agents, especially in chronic conditions like diabetes and Alzheimer's disease.
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40.) Anti-apoptotic and anti-oxidative mechanisms of minocycline against sphingomyelinase/ceramide neurotoxicity: implication in Alzheimer's disease and cerebral ischemia.
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Chen SD1, Yin JH, Hwang CS, Tang CM, Yang DI.
Author information
1Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Abstract
Sphingolipids represent a major class of lipids in which selected family members act as bioactive molecules that control diverse cellular processes, such as proliferation, differentiation, growth, senescence, migration and apoptosis. Emerging evidence reveals that sphingomyelinase/ceramide pathway plays a pivotal role in neurodegenerative diseases that involve mitochondrial dysfunction, oxidative stress and apoptosis. Minocycline, a semi-synthetic second-generation tetracycline derivative in clinical use for infection control, is also considered an effective protective agent in various neurodegenerative diseases in pre-clinical studies. Acting via multiple mechanisms, including anti-inflammatory, anti-oxidative and anti-apoptotic effects, minocycline is a desirable candidate for clinical trials in both acute brain injury as well as chronic neurodegenerative disorders. This review is focused on the anti-apoptotic and anti-oxidative mechanisms of minocycline against neurotoxicity induced by sphingomyelinase/ceramide in relation to neurodegeneration, particularly Alzheimer's disease and cerebral ischemia.
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41.) Clinical potential of minocycline for schizophrenia.
====================================================
CNS Neurol Disord Drug Targets. 2008 Oct;7(4):376-81.
Miyaoka T1.
Author information
1Department of Psychiatry, Shimane University School of Medicine, Izumo, Japan. miyanyan@med.shimane-u.ac.jp
Abstract
Minocycline, an antibiotic of the tetracycline family, has been shown to display neurorestorative or neuroprotective properties in various models of neurodegenerative diseases. In particular, it has been shown to delay motor alterations, inflammation and apoptosis in models of Huntington's disease, amyotrophic lateral sclerosis and Parkinson's disease. Despite controversies about its efficacy, the relative safety and tolerability of minocycline have led to various clinical trials. Recently, we reported the antipsychotic effects of minocycline in patients with schizophrenia. In a pilot investigation, we administered minocycline as an open-label adjunct to antipsychotic medication to patients with schizophrenia. The results of this trial suggested that minocycline might be a safe and effective adjunct to antipsychotic medications, and that augmentation with minocycline may prove to be a viable strategy for "boosting" antipsychotic efficacy and for treating schizophrenia. The present review summarizes the available data supporting the clinical testing of minocycline for patients with schizophrenia. In addition, we extend our discussion to the potential applications of minocycline for combining this treatment with cellular and molecular therapy.
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42.) The potential of minocycline for neuroprotection in human neurologic disease.
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Clin Neuropharmacol. 2004 Nov-Dec;27(6):293-8.
Zemke D1, Majid A.
Author information
1Department of Neurology and Ophthalmology, Michigan State University, East Lansing, Michigan 48824, USA.
Abstract
Minocycline is a member of the tetracycline class of molecules with broad-spectrum antibiotic activity. The unique properties of minocycline result in increased tissue distribution when compared with the other tetracyclines. Of particular interest is the ability of minocycline to diffuse into the central nervous system at clinically effective levels. Aside from its antimicrobial properties, minocycline has been found to have beneficial effects on inflammation, microglial activation, matrix metalloproteinases, nitric oxide production, and apoptotic cell death. Concordantly, minocycline has been found to have neuroprotective effects in animal models of a number of diseases including stroke, multiple sclerosis, and Parkinson disease. The proven safety of minocycline over decades of use as an antibiotic suggests that it may have potential for development into an effective treatment of multiple neurologic conditions in humans.
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43.) Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis.
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Mishra MK1, Basu A.
Author information
1National Brain Research Centre, Manesar, Haryana, India.
Abstract
Minocycline is broadly protective in neurological disease models featuring inflammation and cell death and is being evaluated in clinical trials. Japanese encephalitis virus (JEV) is one of the most important causes of viral encephalitis worldwide. There is no specific treatment for Japanese encephalitis (JE) and no effective antiviral drugs have been discovered. Studies indicate that JE involves profound neuronal loss as well as secondary inflammation caused because of cell death. Minocycline is a semisynthetic second-generation tetracycline that exerts anti-inflammatory and antiapoptotic effects that are completely separate from its antimicrobial action. Because tetracycline treatment is clinically well tolerated, we investigated whether minocycline protects against experimental model of JE. Intravenous inoculation of GP78 strain of JEV in adult mice results in lethal encephalitis and caused primarily because of neuronal death and secondary inflammation caused because of cell death. Minocycline confers complete protection in mice following JEV infection (p < 0.0001). Neuronal apoptosis, microglial activation, active caspase activity, proinflammatory mediators, and viral titer were markedly decreased in minocycline-treated JEV infected mice on ninth day post-infection. Treatment with minocycline may act directly on brain cells, because neuronal cell line Neuro2a were also salvaged from JEV-induced death. Our data suggest that minocycline may be a candidate to consider in human clinical trials for JE patients.
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44.) The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the Lyme disease spirochete Borrelia burgdorferi.
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J Infect Dis. 2009 May 1;199(9):1379-88. doi: 10.1086/597807.
Bernardino AL1, Kaushal D, Philipp MT.
Author information
1Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USA.
Abstract
Tetracyclines moderate inflammatory responses of various etiologies. We hypothesized that tetracyclines, in addition to their antimicrobial function, could exert control over the inflammation elicited by Borrelia burgdorferi. To model systemic effects, we used the human monocytic cell line THP-1; to model effects in the central nervous system, we used rhesus monkey brain astrocytes and microglia. Cells were stimulated with live or sonicated B. burgdorferi or with the lipoprotein outer surface protein A in the presence of increasing concentrations of doxycycline or minocycline. Both antibiotics significantly reduced the production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8 in a dose-dependent manner in all cell types. Microarray analyses of the effect of doxycycline on gene transcription in spirochete-stimulated monocytes revealed that the NFKB and CHUK (alias, IKKA) genes were down-regulated. Functionally, phosphorylation of IkappaBalpha and binding of NF-kappaB to target DNA were both reduced in these cells. Our results suggest that tetracyclines may have a dual therapeutic effect in Lyme disease.
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45.) [Minocycline].
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[Article in French]
Bernier C1, Dréno B.
Author information
1Clinique Dermatologique, Hôtel-Dieu, Place Alexis Ricordeau, 44093 Nantes Cedex 1.
Abstract
Minocycline belongs to the second generation class of cyclines. It was synthesized in 1967 and marketed in 1972. Minocycline has an antiinfectious activity with a spectrum similar to that of other cyclines, notably against Chlamydias, Treponema and Proprionibacterium acnes. The antiinflammatory activity is associated with this antiinfectious action is greater than that of first generation cyclines with specifically a modulator effect on epidermal cytokines. The pharmokinetics of minocycline is characterized by an excellent absorption, a long half-life and an important lipophilic property inducing good tissue distribution. Clinical trials of minocycline have mainly been performed in sexually transmissible diseases and in acne, a field where randomized studies are the most frequent. These trials show that the effect of minocycline is not stronger than first generation cyclines or doxycycline, but that the action is quicker than that of tetracycline at the dose of 500 mg a day. Minocycline is also efficient in nocardiasis, mycobacteriosis, leprosy, Lyme disease, pyoderma gangrenosum, autoimmune bullous dermatitis, Carteaud disease, and prurigo. However, the effect of minocycline in these different conditions has always been evaluated in open trials with a small number of patients. The usual side effects of cyclines, i.e. digestive problems, fungal infections, are less frequent than with first generation cyclines. No photosensitivity has been demonstrated although pigmentations have been described. Dizziness is a specific side effect of minocycline. Furthermore, rare but severe side effects have been reported, including hypersensitivity syndrome, autoimmune hepatitis, and lupus. Regular indications for minocycline in dermatology are acne and three sexually transmissible diseases (mycoplasm, chlamydia, treponema). Proposed dosage is 100 mg per day in sexually transmissible disease with a reduction to 50 mg per day after 15 days in acne.
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 46.) Minocycline attenuates neuronal cell death and improves cognitive impairment in Alzheimer's disease models.
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 Neuropsychopharmacology. 2007 Nov;32(11):2393-404. Epub 2007 Apr 4.
 Choi Y1, Kim HS, Shin KY, Kim EM, Kim M, Kim HS, Park CH, Jeong YH, Yoo J, Lee JP, Chang KA, Kim S, Suh YH.
 Author information

 1Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea.

 Abstract

 Minocycline is a semi-synthetic tetracycline antibiotic that effectively crosses the blood-brain barrier. Minocycline has been reported to have significant neuroprotective effects in models of cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, and Huntington's and Parkinson's diseases. In this study, we demonstrate that minocycline has neuroprotective effects in in vitro and in vivo Alzheimer's disease models. Minocycline was found to attenuate the increases in the phosphorylation of double-stranded RNA-dependent serine/threonine protein kinase, eukaryotic translation initiation factor-2 alpha and caspase 12 activation induced by amyloid beta peptide1-42 treatment in NGF-differentiated PC 12 cells. In addition, increases in the phosphorylation of eukaryotic translation initiation factor-2 alpha were attenuated by administration of minocycline in Tg2576 mice, which harbor mutated human APP695 gene including the Swedish double mutation and amyloid beta peptide(1-42)-infused rats. We found that minocycline administration attenuated deficits in learning and memory in amyloid beta peptide(1-42)-infused rats. Increased phosphorylated state of eukaryotic translation initiation factor-2 alpha is observed in Alzheimer's disease patients' brains and may result in impairment of cognitive functions in Alzheimer's disease patients by decreasing the efficacy of de novo protein synthesis required for synaptic plasticity. On the basis of these results, minocycline may prove to be a good candidate as an effective therapeutic agent for Alzheimer's disease.
 ==============================================================
 47.) Minocycline and neurodegenerative diseases.
 =======================================================
 Behav Brain Res. 2009 Jan 23;196(2):168-79. doi: 10.1016/j.bbr.2008.09.040. Epub 2008 Oct 11.

 Kim HS1, Suh YH.
 Author information

 1Department of Pharmacology, Seoul National University, College of Medicine, Seoul, Republic of Korea.

 Abstract

 Minocycline is a semi-synthetic, second-generation tetracycline analog which is effectively crossing the blood-brain barrier, effective against gram-positive and -negative infections. In addition to its own antimicrobacterial properties, minocycline has been reported to exert neuroprotective effects over various experimental models such as cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease, kainic acid treatment, Huntington' disease and multiple sclerosis. Minocycline has been focused as a neuroprotective agent over neurodegenerative disease since it has been first reported that minocycline has neuroprotective effects in animal models of ischemic injury [Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koisinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA 1998;95:15769-74; Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA 1999;96:13496-500]. Recently, the effect of minocycline on Alzheimer's disease has been also reported. Although its precise primary target is not clear, the action mechanisms of minocycline for neuroprotection reported so far are; via; the inhibition of mitochondrial permeability-transition mediated cytochrome c release from mitochondria, the inhibition of caspase-1 and -3 expressions, and the suppression of microglial activation, involvement in some signaling pathways, metalloprotease activity inhibition. Because of the high tolerance and the excellent penetration into the brain, minocycline has been clinically tried for some neurodegenerative diseases such as stroke, multiple sclerosis, spinal cord injury, amyotropic lateral sclerosis, Hungtington's disease and Parkinson's disease. This review will briefly summarize the effects and action mechanisms of minocycline on neurodegenerative diseases.
 ====================================================================
 48.) Minocycline attenuates Aβ oligomers-induced pro-inflammatory phenotype in primary microglia while enhancing Aβ fibrils phagocytosis.
 ==============================================================
 Neurosci Lett. 2015 Nov 16;609:36-41. doi: 10.1016/j.neulet.2015.10.024. Epub 2015 Oct 17.

 El-Shimy IA1, Heikal OA2, Hamdi N3.
 Author information

 1Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, The German University in Cairo, New Cairo City, Cairo, Egypt.
 2Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, The German University in Cairo, New Cairo City, Cairo, Egypt; Narcotics, Ergogenics & Poisons Department, National Research Center, Giza, Egypt.
 3Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, The German University in Cairo, New Cairo City, Cairo, Egypt. Electronic address: nabila.hamdi@guc.edu.eg.

 Abstract

 Microglia, the brain innate immune cells, are activated in response to amyloid beta (Aβ) resulting in neuroinflammation in AD brains. Recently, two phenotypes have been described for microglia: the pro-inflammatory classical and the anti-inflammatory alternative. Changes in microglia phenotype that control their phagocytic function are yet to be determined. The highly neurotoxic Aβ oligomers (oAβ) formed at an early disease stage induce pro-inflammatory microglia activation releasing neurotoxic mediators and contributing to neurodegeneration. A novel strategy for AD treatment is to attenuate microglia-induced inflammation while maintaining efficient Aβ clearance. Minocycline effectively crosses the blood-brain barrier and has widely reported neuroprotective effects. Yet, its exact mechanism of neuroprotection and its effects on microglia are still unknown. The aim of this study is to investigate the effect of minocycline on the phagocytic uptake of fAβ by primary microglia in relation to their activation state in an inflammatory milieu generated by oAβ or LPS. The study shows that minocycline is able to attenuate oAβ-induced neuroinflammatory response of microglia by inhibiting their pro-inflammatory phenotype activation. In addition, a significant enhancement of fAβ phagocytosis by minocycline- treated microglia is reported for the first time, providing novel insight into its neuroprotective role in AD.
 =========================================================================
 49) Discovering new treatments for Alzheimer's disease by repurposing approved medications.
 ======================================================================
 Curr Top Med Chem. 2013;13(18):2306-27.

 Appleby BS1, Cummings JL.
 Author information

 1Cleveland Clinic Lou Ruvo Center for Brain Health, 9500 Euclid Avenue/U10, Cleveland, OH 44195. applebyb77@gmail.com.

 Abstract

 Alzheimer's disease (AD) is the most common cause of dementia and a major cause of morbidity and mortality. The greatest risk factor for AD is age and as many countries are experiencing an aging population, the expected rise in AD threatens to have serious medical and socioeconomic impact in the coming decades. The only approved medications for AD are symptomatic and there are no currently available disease modifying treatments. Hence, a disease modifying treatment is desperately needed for AD not only for proper care and management of affected patients, but also to reduce society's socioeconomic burden. Developing novel compounds for any indication is a time, effort, and money consuming endeavor and most treatments never make it to market. Other research and development strategies are needed, especially for the treatment of AD. We provide a review of the current literature in assessing possibilities of repurposing medications currently used for non-AD indications. Many different compounds from many different pharmacological classes have already been studied in an AD context. We provide a "pragmatic drug repurposing score" for each of these compounds based on type of studies conducted, number of possible mechanisms of action, efficacy in AD and other neurodegenerative disease studies, tolerability profile, and their ability to cross the blood brain barrier. The current data suggest several compounds worthy of further study as treatments for AD. Compounds with the highest scores include lithium, minocycline, exenatide, valproic acid, methylene blue, and nicotine.
 =============================================================
 50.) Anti-apoptotic and anti-oxidative mechanisms of minocycline against sphingomyelinase/ceramide neurotoxicity: implication in Alzheimer's disease and cerebral ischemia.
 ===========================================================
 Free Radic Res. 2012 Aug;46(8):940-50. doi: 10.3109/10715762.2012.674640. Epub 2012 May 28.

 Chen SD1, Yin JH, Hwang CS, Tang CM, Yang DI.
 Author information

 1Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

 Abstract

 Sphingolipids represent a major class of lipids in which selected family members act as bioactive molecules that control diverse cellular processes, such as proliferation, differentiation, growth, senescence, migration and apoptosis. Emerging evidence reveals that sphingomyelinase/ceramide pathway plays a pivotal role in neurodegenerative diseases that involve mitochondrial dysfunction, oxidative stress and apoptosis. Minocycline, a semi-synthetic second-generation tetracycline derivative in clinical use for infection control, is also considered an effective protective agent in various neurodegenerative diseases in pre-clinical studies. Acting via multiple mechanisms, including anti-inflammatory, anti-oxidative and anti-apoptotic effects, minocycline is a desirable candidate for clinical trials in both acute brain injury as well as chronic neurodegenerative disorders. This review is focused on the anti-apoptotic and anti-oxidative mechanisms of minocycline against neurotoxicity induced by sphingomyelinase/ceramide in relation to neurodegeneration, particularly Alzheimer's disease and cerebral ischemia.
 ===============================================================
 51.) Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology.
 =========================================================
 J Neuroinflammation. 2012 Apr 2;9:62. doi: 10.1186/1742-2094-9-62.

 Ferretti MT1, Allard S, Partridge V, Ducatenzeiler A, Cuello AC.
 Author information

 1Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC H3G 1Y6, Canada.

 Abstract
 BACKGROUND:

 A growing body of evidence indicates that inflammation is one of the earliest neuropathological events in Alzheimer's disease. Accordingly, we have recently shown the occurrence of an early, pro-inflammatory reaction in the hippocampus of young, three-month-old transgenic McGill-Thy1-APP mice in the absence of amyloid plaques but associated with intracellular accumulation of amyloid beta petide oligomers. The role of such a pro-inflammatory process in the progression of the pathology remained to be elucidated.
 METHODS AND RESULTS:

 To clarify this we administered minocycline, a tetracyclic derivative with anti-inflammatory and neuroprotective properties, to young, pre-plaque McGill-Thy1-APP mice for one month. The treatment ended at the age of three months, when the mice were still devoid of plaques. Minocycline treatment corrected the up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 observed in young transgenic placebo mice. Furthermore, the down-regulation of inflammatory markers correlated with a reduction in amyloid precursor protein levels and amyloid precursor protein-related products. Beta-site amyloid precursor protein cleaving enzyme 1 activity and levels were found to be up-regulated in transgenic placebo mice, while minocycline treatment restored these levels to normality. The anti-inflammatory and beta-secretase 1 effects could be partly explained by the inhibition of the nuclear factor kappa B pathway.
 CONCLUSIONS:

 Our study suggests that the pharmacological modulation of neuroinflammation might represent a promising approach for preventing or delaying the development of Alzheimer's disease neuropathology at its initial, pre-clinical stages. The results open new vistas to the interplay between inflammation and amyloid pathology.
 ===================================================
 52.) Reductions in amyloid-beta-derived neuroinflammation, with minocycline, restore cognition but do not significantly affect tau hyperphosphorylation.
 ==================================================
 Parachikova A1, Vasilevko V, Cribbs DH, LaFerla FM, Green KN.
 Author information

 1Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4545, USA.

 Abstract

 Cognitive decline in Alzheimer's disease (AD) occurs as a result of the buildup of pathological proteins and downstream events including an elevated and altered inflammatory response. Inflammation has previously been linked to increased abnormal phosphorylation of tau protein. To determine if endogenous amyloid-beta (Abeta)-induced neuroinflammation drives tau phosphorylation in vivo, we treated 8-month-old 3xTg-AD with minocycline, an anti-inflammatory agent, to assess how it influenced cognitive decline and development of pathology. 4 months of treatment restored cognition to non-transgenic performance. Inflammatory profiling revealed a marked decrease in GFAP, TNFalpha, and IL6 and an increase in the CXCL1 chemokines KC and MIP1a. Minocycline also reduced levels of insoluble Abeta and soluble fibrils. Despite reducing levels of the tau kinase cdk5 coactivator p25, minocycline did not have wide effects on tau pathology with only one phospho-epitope showing reduction with treatment (S212/S214). The sum of these findings shows that reduction of the inflammatory events in an AD mouse model prevents cognitive deficits associated with pathology, but that endogenous Abeta-derived neuroinflammation does not contribute significantly to the development of tau pathology.
 ===========================================================
 53.) Minocycline may be useful to prevent/treat postoperative cognitive decline in elderly patients.
 ==========================================================
 Med Hypotheses. 2011 May;76(5):733-6. doi: 10.1016/j.mehy.2011.02.010. Epub 2011 Feb 26.

 Fan L1, Wang TL, Xu YC, Ma YH, Ye WG.
 Author information

 1Department of Anaesthesiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

 Abstract

 Postoperative cognitive dysfunction (POCD) is reported to occur frequently after all types especially cardiac surgery in elderly patients. It can be short-term or long-term and some cases even develop into Alzheimer's disease (AD). Although multi-risk factors associated with POCD have been identified, the etiology and pathophysiological mechanisms of this surgical complication remain elusive. Therefore, developing strategies for preventing or treating POCD is still challenging. However, increasing evidence suggests that central and systemic inflammation triggered by surgery likely plays a fundamental role in POCD developing and progression. Minocycline, a tetracycline derivative with anti-inflammatory properties, has been shown to be effective in treating neuroinflammatory related conditions or neurodegenerative diseases such as AD, Parkinson's disease, Huntington's disease. Considering that inflammation may be a potential factor of POCD and minocycline is effective in improving cognitive dysfunction induced by inflammation, we hypothesize that minocycline may be useful to treat/prevent the POCD development after surgery in elderly patients.
  ======================================================================
()()()(()()()()()()()()( LO MALO () THE BAD ()()()()()()()()()()()()()()
======================================================================
1.) Minocycline induced autoimmune hepatitis and systemic lupus
erythematosus-like syndrome [see comments]
2.) Minocycline and Lupuslike Syndrome in Acne Patients
3.) Minocycline-induced lupus.
4.) Minocycline related lupus.
5.) Acute hepatitis and drug-related lupus induced by minocycline treatment.
6.) Minocycline-induced pneumonitis with bilateral hilar lymphadenopathy
and pleural effusion.
7.) Comparative safety of tetracycline, minocycline, and doxycycline.
8.) Serious adverse reactions induced by minocycline. Report of 13
patients and review of the literature.
9.) [Side effects of minocycline in the treatment of acne vulgaris]
10.) Serious dermatologic reactions in children.
11.) Serum sickness-like syndrome associated with minocycline therapy.
12.) Minocycline-induced loss of potassium from erythrocytes:
identification of a family with an augmented response.
======================================================================
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======================================================================
13.) Minocycline-induced hyperpigmentation in leprosy.
14.) Psoriatic arthritis and minocycline induced autoantibodies.
15.) Minocycline hydrochloride hyperpigmentation complicating treatment of
pyoderma gangrenosum.
16.) Minocycline-induced oral pigmentation.
17.) Nodular hyperplasia, black thyroid, and chronic minocycline ingestion
in a teenager.
18.) Black bones following long-term minocycline treatment.
19.) Pigmented postacne osteoma cutis in a patient treated with
minocycline: report and review of the literature.
20.) ANA (+) ANCA (+) systemic vasculitis associated with the use of minocycline: case-based review.
=========================================================================
()()()()()()()()()()( LO MALO () THE BAD ()()()()()()()()()()()()()()()()
=========================================================================
1.) Minocycline induced autoimmune hepatitis and systemic lupus
erythematosus-like syndrome [see comments]
=========================================================================
Author
Gough A; Chapman S; Wagstaff K; Emery P; Elias E
Address
Department of Rheumatology, Harrogate District Hospital.
Source
BMJ, 312(7024):169-72 1996 Jan 20
Abstract
Monocycline is the most widely prescribed systemic antibiotic for acne
largely because it needs to be given only once or twice a day and seems not
to induce resistance. Up to April 1994 11 cases of minocycline induced
systemic lupus erythematosus and 16 cases of hepatitis had been reported to
the Committee on Safety of Medicines. An analysis of these cases together
with seven other cases shows the severity of some of these reactions. Two
patients died while taking the drug for acne and a further patient needed a
liver transplant. Acne itself can induce arthritis and is often seen in
association with autoimmine liver disease, but the clinical and biochemical
resolution seen after withdrawal of the drug, despite deterioration of the
acne, suggests a drug reaction. In five cases re-exposure led to
recurrence. Because reactions may be severe early recognition is important
to aid recovery and also to avoid invasive investigations and treatments
such as corticosteroids and immunosuppresants. Safer alternatives should be
considered for treating acne.

=========================================================================
2.) Minocycline and Lupuslike Syndrome in Acne Patients
=========================================================================
Miriam C. J. M. Sturkenboom, PhD, PharmD, MSc; Christoph R. Meier, PhD,
MSc; Hershel Jick, MD; Bruno H. C. Stricker, PhD, MB
Arch Intern Med. 1999;159:493-497

Background: Recently several case reports described the association between
minocycline and lupuslike syndrome. Minocycline, one of
the tetracyclines, is widely used to treat acne. We aimed to examine the
association of exposure to minocycline and other tetracyclines with the
development
of lupuslike syndrome.

Methods: We conducted a nested case-control study in a cohort of 27,688 acne
patients aged 15 to 29 years, using data automatically recorded on general
practitioners' office computers in the United Kingdom. Controls were matched
to cases on age, sex, and practice. The main outcome was lupuslike syndrome
defined as the occurrence of polyarthritis or polyarthralgia of unknown
origin,
with negative rheumatoid factor or latex agglutination test, positive or
unmeasured antinuclear factor, elevated or unmeasured erythrocyte
sedimentation rate, and absence of or unmeasured antinative DNA antibody
levels.

Results: We identified 29 cases and selected 152 controls. Current single
use of
minocycline was associated with an 8.5-fold (95% confidence interval [CI],
2.1-35) increased risk of developing lupuslike syndrome compared with
nonusers and past users of tetracyclines combined. The risk of past
exposure to
any of the tetracyclines was closely similar to nonuse (relative risk, 1.3;
95%
CI, 0.5-3.3). Current use of doxycycline, oxytetracycline, or tetracycline
combined was associated with a 1.7-fold (95% CI, 0.4-8.1) increase of risk.
The
risk increased with longer use.

Conclusion: Current use of minocycline increased the risk of developing
lupuslike syndrome 8.5-fold in the cohort of young acne patients. The
effect was
stronger in longer-term users. However, the absolute risk of developing
lupuslike syndrome seems to be relatively low.

=========================================================================
3.) Minocycline-induced lupus.
=========================================================================
Author
Farver DK
Address
College of Pharmacy, South Dakota State University, Brookings, USA.
dfarver@sunflowr.usd.edu
Source
Ann Pharmacother, 31(10):1160-3 1997 Oct
Abstract
OBJECTIVE: To report a case of drug-induced lupus occurring 5 months after
the initiation of minocycline therapy for acne. DATA SOURCE: Case report
information was obtained from the physician, patient's family, and the
medical record. MEDLINE and Index Medicus were searched to obtain relevant
published literature from 1966 to 1996. CASE SUMMARY: A 14-year-old white
girl developed symptoms of myalgias, arthralgias, polyarthritis, and
flushed face. The antinuclear antibody test was positive. Minocycline was
discontinued and the patient's condition dramatically improved within 7
days. CONCLUSIONS: Healthcare providers should recognize early common and
unusual symptoms of minocycline-induced lupus in adolescents being treated
for acne.

=========================================================================
4.) Minocycline related lupus.
=========================================================================
Author
Masson C; Chevailler A; Pascaretti C; Legrand E; Br´egeon C; Audran M
Address
Service de Rhumatologie, CHU d'Angers, France.
Source
J Rheumatol, 23(12):2160-1 1996 Dec
Abstract
The determination of a factor triggering lupus-like symptoms could yield
new insights into the management of rheumatic disease. We describe a case
of minocycline related lupus in a young patient positive for HLA-DR2 who
was prescribed minocycline 4 times for mild acne and developed rheumatic
symptoms each time. We review 8 other cases.

=========================================================================
5.) Acute hepatitis and drug-related lupus induced by minocycline treatment.
=========================================================================
Author
Golstein PE; Deviere J; Cremer M
Address
Department of Gastroenterology, Erasmus Hospital, Universit´e Libre de
Bruxelles, Belgium.
Source
Am J Gastroenterol, 92(1):143-6 1997 Jan
Abstract
Minocycline is widely prescribed for long-term treatment in acne. Major
side effects are rare and include hepatitis and drug-related lupus.
Hepatitis can be early and acute or late and chronic, whereas lupus
presents as a tardive and insidious disease. We report a case of
minocycline-induced lupus initially presenting as acute hepatitis, evolving
to chronic cytolysis, in a young man treated for facial acne.

=========================================================================
6.) Minocycline-induced pneumonitis with bilateral hilar lymphadenopathy
and pleural effusion.
=========================================================================
ARTICLE SOURCE: Intern Med (Japan), Mar 1994, 33(3) p177-9
AUTHOR(S): Bando T; Fujimura M; Noda Y; Hirose J; Ohta G; Matsuda T
PUBLICATION TYPE: JOURNAL ARTICLE; REVIEW (12 references); REVIEW,
ABSTRACT: A 65-year-old man developed respiratory failure with diffuse
interstitial shadow, bilateral pleural effusion, and bilateral hilar
lymphadenopathy on chest X-ray and CT, after intravenous administration of
minocycline. Corticosteroid therapy was effective. The findings from
bronchoalveolar lavage (BAL) and transbronchial lung biopsy were compatible
with eosinophilic pneumonia. Provocation test supported this diagnosis, but
the lymphocyte stimulation test was negative. A review of the literature
and the diagnoses of drug-induced pulmonary diseases are discussed.

=========================================================================
7.) Comparative safety of tetracycline, minocycline, and doxycycline.
=========================================================================
Author
Shapiro LE; Knowles SR; Shear NH
Address
Department of Medicine, Sunnybrook Hospital, University of Toronto Medical
School, Ontario, Canada.
Source
Arch Dermatol, 133(10):1224-30 1997 Oct
Abstract
BACKGROUND: Because minocycline can cause serious adverse events including
hypersensitivity syndrome reaction (HSR), serum sicknesslike reaction
(SSLR), and drug-induced lupus, a follow-up study based on a retrospective
review of our Drug Safety Clinic and the Health Protection Branch databases
and a literature review was conducted to determine if similar rare events
are associated with tetracycline and doxycycline. Cases of isolated single
organ dysfunction (SOD) attributable to the use of these antibiotics also
were identified. OBSERVATIONS: Nineteen cases of HSR due to minocycline, 2
due to tetracycline, and 1 due to doxycycline were identified. Eleven cases
of SSLR due to minocycline, 3 due to tetracycline, and 2 due to doxycycline
were identified. All 33 cases of drug-induced lupus were attributable to
minocycline. Forty cases of SOD from minocycline, 37 cases from
tetracycline, and 6 from doxycycline were detected. Hypersensitivity
syndrome reaction, SSLR, and SOD occur on average within 4 weeks of
therapy, whereas minocycline-induced lupus occurs on average 2 years after
the initiation of therapy. CONCLUSIONS: Early serious events occurring
during the course of tetracycline antibiotic treatment include HSR, SSLR,
and SOD. Drug-induced lupus, which occurs late in the course of therapy, is
reported only with minocycline. We theorize that minocycline metabolism may
account for the increased frequency of serious adverse events with this drug.

=========================================================================
8.) Serious adverse reactions induced by minocycline. Report of 13
patients and review of the literature.
=========================================================================
Author
Knowles SR; Shapiro L; Shear NH
Address
Division of Clinical Pharmacology, Sunnybrook Health Science Centre,
Toronto, Ontario.
Source
Arch Dermatol, 132(8):934-9 1996 Aug
Abstract
BACKGROUND: Minocycline has been reported to cause serious, albeit rare,
adverse events, including serum sickness-like reaction, hypersensitivity
syndrome reaction, and drug-induced lupus. A retrospective review of
patients seen in our Adverse Drug Reaction Clinic as well as information
obtained from the Health Protection Branch was done to identify patients
with minocycline-induced reactions. In addition, the literature concerning
serious reactions to minocycline was reviewed. OBSERVATIONS: Six patients
with a hypersensitivity syndrome reaction, 6 patients with a serum
sickness-like reaction, and 1 patient who had symptoms consistent with
drug-induced lupus were identified. A review of the literature identified
11 cases of hypersensitivity syndrome reaction, 1 case of serum
sickness-like reaction, and 24 cases of drug-induced lupus. Serum
sickness-like reactions occur sooner than hypersensitivity syndrome
reactions (15.6 vs 23.7 days, P = .04). Drug-induced lupus occurs on
average 2 years after the start of minocycline therapy. CONCLUSIONS:
Dermatologists need to be aware of the serious adverse reactions that can
develop after minocycline use. In patients who may require long-term
therapy with minocycline ( > 1 year), we suggest that antinuclear antibody
and hepatic transaminase levels be determined at baseline. Rechallenge with
minocycline or other tetracyclines is currently not recommended for
patients who develop these serious reactions.
Language

=========================================================================
9.) [Side effects of minocycline in the treatment of acne vulgaris]
=========================================================================
Author
Hoefnagel JJ; van Leeuwen RL; Mattie H; Bastiaens MT
Address
Afd. Dermatologie, Leids Universitair Medisch Centrum, Leiden.
Source
Ned Tijdschr Geneeskd, 141(29):1424-7 1997 Jul 19
Abstract
Minocycline is the most commonly used systemic antibiotic in the long-term
treatment (weeks to months) of severe acne vulgaris. Currently much
attention is being paid in the Dutch and international literature to the
safety of minocycline, after several reports on serious adverse events. The
clinical efficacy of minocycline in the treatment of acne vulgaris is
better than that of tetracycline and equal to that of doxycycline. The
serious adverse events of minocycline therapy described consist of
hyperpigmentation of various tissues, autoimmune disorders (systemic lupus
erythematosus, autoimmune hepatitis) and serious hypersensitivity reactions
(hypersensitivity syndrome reaction, pneumonitis and eosinophilia, and
serum sickness-like syndrome). In relation to the number of prescriptions,
the number of serious adverse events of minocycline described is small.
However, it is very important that prescribing doctors should be aware of
the possibility of these adverse events occurring during long-term
minocycline therapy and able to recognize the characteristic symptoms at an
early stage.

=========================================================================
10.) Serious dermatologic reactions in children.
=========================================================================
Author
Knowles S; Shapiro L; Shear NH
Address
Department of Clinical Pharmacology, Sunnybrook Health Science Centre,
Toronto, Ontario, Canada.
Source
Curr Opin Pediatr, 9(4):388-95 1997 Aug
Abstract
Although serious reactions comprise only a small percentage of total
adverse drug reactions, they are important in terms of morbidity and
potential mortality. An update on serious dermatologic reactions in
children is presented including serum sickness-like reactions due to
cefaclor, hypersensitivity syndrome reactions (HSRs), and drug-induced
pseudoporphyria. More detailed information on minocycline-induced reactions
including drug-induced lupus and HSRs and lamotrigine-induced toxic
epidermal necrolysis and Stevens-Johnson syndrome will be discussed.

=========================================================================
11.) Serum sickness-like syndrome associated with minocycline therapy.
=========================================================================
ARTICLE SOURCE: Allergy (Denmark), May 1990, 45(4) p313-5
AUTHOR(S): Puyana J; Urena V; Quirce S; Fernandez-Rivas M; Cuevas M; Fraj J
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: A 19 year-old youth was taking oral minocycline and after 8 days
he presented all four cardinal symptoms of serum sickness (urticaria,
fever, lymphadenopathy and joint symptoms). C3, C4 and CH50 evolution
imitate experimental serum sickness complement evolution. We exclude other
causes of this syndrome. Although other hypersensitivity reactions have
occurred with minocycline usage, to our knowledge serum sickness-like
syndrome has not been previously reported with this drug.

=========================================================================
12.) Minocycline-induced loss of potassium from erythrocytes:
identification of a family with an augmented response.
=========================================================================
ARTICLE SOURCE: J Infect Dis (United States), Oct 1978, 138(4) p455-62
AUTHOR(S): Kornguth ML; Kunin CM
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: The effect of several tetracycline antibiotics of human
erythrocytes was examined because of previous findings that these drugs
bind to erythrocyte membranes. Minocycline and cetocycline, two highly
lipid-soluble analogues, but not tetracycline, induced loss of K+ from red
blood cells. Loss of K+ increased linearly with time of incubation,
concentration of minocycline, and temperature. The effect of minocycline
was inhibited by plasma and calcium. The cells from one volunteer
consistently showed an augmented response to minocycline; similar findings
for family members of the volunteer suggested a dominant autosomal mode of
inheritance. The only abnormality noted in the subject was mild
reticulocytosis and a slightly reduced K+ content in his red blood cells.
Preliminary studies did not demonstrate alterations in protein composition
of his red blood cell membranes, enhanced osmotic fragility, or defects in
Ca++-dependent or ouabain-sensitive (Na+-K+)-dependent adenosine
triphosphatase activity. The exact site of the minocycline effect remains
to be determined.

=========================================================================
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=========================================================================
13.) Minocycline-induced hyperpigmentation in leprosy.
=========================================================================
Author
Fleming CJ; Hunt MJ; Salisbury EL; McCarthy SW; Barnetson RS
Address
Department of Dermatology, Royal Prince Alfred Hospital, New South Wales,
Australia.
Source
Br J Dermatol, 134(4):784-7 1996 Apr
Abstract
A 36-year-old man was treated with dapsone, rifampicin and clofazimine for
borderline lepromatous leprosy. After 9 months, his leprosy plaques became
progressively more red and after 23 months, the clofazimine was stopped and
he was given minocycline instead. Six weeks later, he developed blue-black
pigmentation in his leprosy lesions. The histology was consistent with
minocycline-induced hyperpigmentation. This is the first report of
minocycline-induced pigmentation in leprosy. We suggest it is important to
consider this side-effect before the administration of minocycline in
leprosy, particularly if it is prescribed in place of clofazimine.

=========================================================================
14.) Psoriatic arthritis and minocycline induced autoantibodies.
=========================================================================
Leitch DN; Haslock DI
Department of Rheumatology, South Cleveland Hospital, Middlesbrough,
Cleveland.
Clin Rheumatol (BELGIUM) May 1997 16 (3) p317-8 ISSN: 0770-3198
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9710
Subfile: INDEX MEDICUS
A case of psoriatic arthritis where diagnosis was originally complicated
by the
presence of minocycline-induced auto-antibodies and hepatic dysfunction.
The range
of auto-antibodies associated with minocycline includes ds DNA and SCL 70.

=========================================================================
15.) Minocycline hydrochloride hyperpigmentation complicating treatment of
pyoderma gangrenosum.
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ARTICLE SOURCE: J Dermatol (Japan), Dec 1994, 21(12) p965-7
AUTHOR(S): Miralles ES; Nunez M; Perez B; Ledo A
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Minocycline-associated hyperpigmentation is an uncommon side
effect. We report the case of a patient with pyoderma gangrenosum
successfully treated with oral minocycline but complicated by marked
hyperpigmentation in his pyoderma gangrenosum and acne scars. One of the
clinical forms of minocycline hyperpigmentation includes dark-blue or black
macules in depressed acne scars or other sites of skin inflammation; this
pattern seems to be independent of the total cumulative dose and the skin
process.

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16.) Minocycline-induced oral pigmentation.
=========================================================================
ARTICLE SOURCE: J Am Acad Dermatol (United States), Feb 1994, 30(2 Pt 2)
p350-4
AUTHOR(S): Siller GM; Tod MA; Savage NW
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Oral mucosal pigmentation is an infrequently reported side
effect of minocycline. Two patients with minocycline deposition within
teeth and bone, demonstrated by fluorescence microscopy, are described.
Minocycline is the only tetracycline reported to cause discoloration of the
oral mucosa. This may be the result of deposition of an insoluble
degradation product of minocycline in the underlying bone. Pigmentation is
not necessarily dose-dependent and may take months or years to resolve.

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17.) Nodular hyperplasia, black thyroid, and chronic minocycline ingestion
in a teenager.
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ARTICLE SOURCE: Arch Surg (United States), Dec 1992, 127(12) p1476-7
AUTHOR(S): Folsom DL; Gauderer MW; Dahms WT
PUBLICATION TYPE: JOURNAL ARTICLE; REVIEW (7 references); REVIEW OF
REPORTED CASES
ABSTRACT: An 18-year-old man with left-lobe thyroid hemiagenesis underwent
isthmectomy for management of a nodule that failed to take up radioactive
iodine during a nuclear scan. The resected tissue, which demonstrated
nodular hyperplasia, and the remaining right lobe, were black. The
association between deep staining and chronic minocycline ingestion was
subsequently recognized. Twelve years later, the patient remained
asymptomatic, suggesting that complete resection of tetracycline-stained
thyroid tissue is unnecessary.

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18.) Black bones following long-term minocycline treatment.
=========================================================================
ARTICLE SOURCE: Arch Pathol Lab Med (United States), Sep 1991, 115(9)
p939-41
AUTHOR(S): Rumbak MJ; Pitcock JA; Palmieri GM; Robertson JT
PUBLICATION TYPE: JOURNAL ARTICLE; REVIEW (16 references); REVIEW OF
REPORTED CASES
ABSTRACT: During a surgical procedure, black vertebrae were observed in a
42-year-old white woman. An undecalcified iliac crest bone biopsy specimen
revealed intense fluorescence compatible with tetracycline labeling and
osteoporosis. A urinary screening test was negative for amino acids. The
patient had been treated with minocycline hydrochloride (100 to 300 mg/d)
for at least 6 years. Since minocycline is known to discolor many body
tissues, it is likely that the black discoloration of bone in our patient
was caused by the long-term intake of the antibiotic.

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19.) Pigmented postacne osteoma cutis in a patient treated with
minocycline: report and review of the literature.
=========================================================================
ARTICLE SOURCE: J Am Acad Dermatol (United States), May 1991, 24(5 Pt 2)
p851-3
AUTHOR(S): Moritz DL; Elewski B
PUBLICATION TYPE: JOURNAL ARTICLE; REVIEW (19 references); REVIEW, TUTORIAL
ABSTRACT: Postacne osteoma cutis is a rare complication of acne vulgaris.
If it occurs during a course of tetracycline or minocycline therapy,
pigmented osteomas can occur as a result of tetracycline or minocycline
bone complexes. We report a case of pigmented postacne osteoma cutis that
developed after extensive acne surgery and a 2- to 3-month course of
minocycline. Previously reported cases have been treated surgically, but
our patient responded to 0.05% tretinoin cream, with transepidermal
elimination of some osteomas.

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20.) ANA (+) ANCA (+) systemic vasculitis associated with the use of minocycline: case-based review.
==================================================
Clin Rheumatol. 2013 Jul;32(7):1099-106. doi: 10.1007/s10067-013-2245-z. Epub 2013 Apr 21.

Lenert P1, Icardi M, Dahmoush L.
Author information

1Department of Internal Medicine, Carver College of Medicine, The University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA. petar-lenert@uiowa.edu

Abstract

Minocycline is a synthetic tetracycline-derived antibiotic with significant anti-inflammatory properties that may benefit patients with rheumatoid arthritis. Surprisingly, chronic exposure to minocycline can also cause a breach in immunologic tolerance resulting in a variety of autoimmune syndromes such as drug-induced lupus or autoimmune hepatitis. Vasculitis, most commonly resembling cutaneous polyarteritis nodosa, has also been seen in patients taking this drug. Herein, we present a case of biopsy-proven systemic vasculitis presenting as an ANA (+) ANCA (+) polyarteritis nodosa-like syndrome in a male patient who was taking minocycline for his acne for approximately 2 years. Patient initially presented with constitutional symptoms such as profound weight loss and fatigue, along with myalgias, oligoarticular arthritis, and livedo reticularis. About 2 months later, he developed a severe left testicular pain. Biopsy showed vasculitis complicated with the infarction of the left testis. Angiography revealed microaneurysms in the renal and splenic circulation. Stopping the offending drug, along with the short course of prednisone and hydroxychloroquine, resulted in prompt resolution of his symptoms. We additionally present a comprehensive review of biopsy-proven cases of vasculitis associated with chronic minocycline treatment focusing on its pathogenesis and clinical manifestations.
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