Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new minocin research articles will be listed here shortly after becoming available to us.
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Medical research on minocin
[Is good old minocycline a new neuroprotective drug?]
Rev Neurol. 2008 Jul 1-15; 47(1): 31-8
Melero-Fernández de Mera RM, García-Martínez E, Fernández-Gómez FJ, Hernández-Guijo JM, Aguirre N, Galindo MF, Jordán J
INTRODUCTION: During the last decade, the neuroprotective effects of minocycline have been a matter of an intense debate. A broad amount of contradictory studies can be found in the scientific literature, going from neuroprotection to the exacerbation of toxicity in diverse experimental models. Such differences could be the result of minocycline acting on multiple pharmacological targets. DEVELOPMENT: In the present review we will go over these pharmacological targets and the effects derived from their modulation by minocycline. Among others, its antioxidant activity derived from its chemical structure or its modulator effect on several enzymes such as nitric oxide synthase will be reviewed. Furthermore, the effects of minocycline on the intracellular pathways implicated in neurodegenerative processes including apoptosis stages, activation decision and execution will be addressed. CONCLUSIONS: All the mechanisms described herein have not escaped to a scientific community needed of new therapeutic drugs for the treatment of neurodegenerative conditions. However, the sparse clinical trials carried out so far are mainly aimed at assessing its tolerability and safety or are still in progress. We believe that more studies, both clinical and pre-clinical, should be carried out in order to ascertain the therapeutic window and the neurodegenerative disorders in which minocycline could be useful.
Cerebellum. 2008 Jul 1;
Viscomi MT, Latini L, Florenzano F, Bernardi G, Molinari M
Degenerative changes in areas remote from the primary lesion site have been linked to the clinical outcome of focal brain damage, and inflammatory mechanisms have been considered to play a key role in the pathogenesis of these remote cell death phenomena. Minocycline is a tetracycline derivative, therapeutically effective in various experimental models of central nervous system (CNS) injuries that include inflammatory and apoptotic mechanisms, although recent findings have yielded mixed results. In this study, we investigated the effectiveness of minocycline treatment in reducing remote cell death. Glial activation and neuronal loss in precerebellar stations following cerebellar lesion were investigated using immunohistochemistry and Western blot techniques. Our results show that minocycline was effective in reducing microglial activations in axotomized precerebellar nuclei, but failed to mitigate either astrocytic response or neuronal loss. This finding supports the role of minocycline in modulating inflammatory response after CNS lesion and suggests its ineffectiveness in influencing degenerative phenomena in areas remote from the primary lesion site.
Ned Tijdschr Geneeskd. 2008 May 31; 152(22): 1271-5
Kertzman MG, Smeets JG, Boukes FS, Goudswaard AN
The 1999 practice guideline 'Acne vulgaris' from the Dutch College of General Practitioners has been revised. Benzoyl peroxide and local retinoids are first choice in local treatment of acne. When treatment with oral antibiotics is indicated, doxycycline is first choice. Use of minocycline is not recommended in general practice. It is recommended that both local and oral antibiotics are always combined with local benzoyl peroxide or a local retinoid. Oral contraceptives are only recommended in women with acne who also desire contraception. Use of oral contraceptives containing cyproterone acetate is no longer recommended in women with acne, because they are not more effective than other oral contraceptives. Treatment with oral isotretinoin may be given by the general practitioner, as long as the treatment guidelines are carefully followed.
Exposure to metal ions regulates mRNA levels of APP and BACE1 in PC12 cells: Blockage by curcumin.
Neurosci Lett. 2008 Aug 8; 440(3): 344-7
Lin R, Chen X, Li W, Han Y, Liu P, Pi R
Amyloid beta peptide (Abeta), generated by proteolytic cleavage of the amyloid precursor protein (APP), play a pivotal role in the pathogenesis of Alzheimer's disease (AD). The key step in the generation of Abeta is cleavage of APP by beta-site APP-cleaving enzyme 1 (BACE1). There is increasing evidence supporting an interaction between APP, Abeta and metal ions. Both APP and Abeta affect ion homeostasis. Conversely, metal ions may interact with several AD-associated pathways involved in neurofibrillary tangle formation, secretase cleavage of APP, proteolytic degradation of Abeta and the generation of reactive oxygen species. However, the underlying mechanisms remain elusive. Here we first reported the differential effects of AD-related metal ions at subtoxic concentrations on the transcription levels of APP and BACE1 in PC12 cells. Copper (Cu(2+), 50-100muM) and manganese (Mn(2+), 50-100muM) potently increased the expression of both APP and BACE1 in a time- and concentration-dependent pattern, while zinc (Zn(2+)), iron (Fe(2+)) and aluminum (Al(3+)) did not. To uncover the mechanism(s) of the increasing expression by these ions, we observed the effects of several antioxidants and some specific inhibitors on the up-expression of APP and BACE1 by metal ions. Curcumin almost completely blocked the effects of these irons, while minocycline and sodium ferulate slightly suppressed the increased BACE1 mRNA level. Signaling pathway specific inhibitors PD98059, SB203580 and CEP11004 modestly blocked the up-transcription of APP induced by copper. These results suggest that these irons cause differential effects on the expression of APP and BACE1 in PC12 cells, and curcumin can significantly reverse their effects.
J Dermatol. 2008 Jun; 35(6): 346-53
Fukuda H, Saotome A, Usami N, Urushibata O, Mukai H
Nocardiosis is a mixed suppurative and granulomatous inflammatory disease caused by infection with Nocardia organisms, a group of aerobic actinomycetes. We recently encountered a 25-year-old woman with posttraumatic nocardiosis of the lower extremities. The clinical symptoms noted during her first visit included erythematous swelling of the right knee accompanied by white maceration of the center of the knee and erosions, shallow ulcers and satellite pustules. In addition, multiple erythematous areas (up to the size of the tip of the thumb) were linearly distributed on the right thigh. These lesions were painful, and right inguinal lymphadenopathy was also noted. No lesion was found in internal organs such as the lungs. Histopathologically, signs of nonspecific granulomatous inflammation were observed, as well as several filamentous branching bacilli positive on Grocott stain. The organisms isolated from culture of pus were acid-fast, Gram-positive long rods. The isolated strain was finally identified as Nocardia brasiliensis. The patient was therefore diagnosed with lymphocutaneous type of primary cutaneous nocardiosis caused by N. brasiliensis. Drip infusion of flomoxef sodium was initially performed to treat her condition. Because of exacerbation of erythematous swelling of the right knee and an increase in number of pustules, treatment was switched to oral minocycline hydrochloride therapy. The disease healed 9 weeks after the start of oral minocycline hydrochloride therapy. Our patient was free of systemic immunosuppression and was neither under 10 nor over 65 years of age. She may therefore be considered a rare case of lymphocutaneous type of nocardiosis. We present this case and discuss reported cases of primary cutaneous nocardiosis due to N. brasiliensis in Japan.
Evidence-based therapy for cutaneous sarcoidosis.
Drugs. 2008; 68(10): 1361-83
Doherty CB, Rosen T
Although healthcare providers have arrived at a relatively comfortable zone of accepted clinical practice in the management of cutaneous sarcoidosis, virtually every treatment is based on minimal evidence-based data and relies almost exclusively on anecdotal information. Although it would be convenient to blame this state of affairs on the lack of certainty about disease aetiology, the unavoidable fact is that little has been executed, even in the realm of well designed comparative trials. Nonetheless, worldwide accepted standard therapies for sarcoidosis include the administration of corticosteroids, antimalarials and methotrexate. A stepwise approach to patient care is appropriate, and potent topical corticosteroids (e.g. clobetasol) or repeated intralesional injections of triamcinolone (3-10 mg/mL) may be all that is needed in mild skin-limited disease. In patients requiring systemic therapy for recalcitrant or deforming skin lesions (or for widespread disease), corticosteroids (e.g. prednisone 40-80 mg/day, tapered accordingly) used alone or in combination with antimalarials or methotrexate may be indicated. Antimalarials and methotrexate are considered second-line interventions and may be used as monotherapy for steroid-resistant sarcoidosis or in patients unable to tolerate steroids. Given the concern regarding ocular toxicity, the maximum dosages of chloroquine and hydroxychloroquine should not exceed 3.5 and 6.5 mg/kg/day, respectively. Methotrexate is given in weekly doses of 10-30 mg, with the caveat that haematological, gastrointestinal, pulmonary and hepatic toxicities are possible. Despite universal acceptance as standard care, the aforementioned treatments often result in an incomplete clinical response or unacceptable adverse events. In such situations, more innovative treatment options may be used. Treatments that may well gain widespread future use include the tumour necrosis factor-alpha inhibitors infliximab and adalimumab. Experience is limited, but early reports are promising. Infliximab is administered via intravenous infusion at doses of 3-10 mg/kg at 0, 2 and 6 weeks and as indicated thereafter, whereas adalimumab is injected subcutaneously at doses of 40 mg either weekly or every 2 weeks. Because adalimumab is not approved for the management of sarcoidosis, the optimum dose administration interval is uncertain. However, it has been given in both weekly and every other week regimens. Isotretinoin, 0.5-2 mg/kg/day, has been used successfully in a handful of reported cases. However, the teratogenic potential of isotretinoin is often prohibitive considering that the primary demographic group likely to develop sarcoidosis is women of childbearing potential. Thalidomide at dosages of 50 to >400 mg/day has limited, albeit promising, supporting data. However, access is restricted in many countries because of a deserved pregnancy category X rating. Melatonin (20 mg/day) and allopurinol (100-300 mg/day) are not well studied in cutaneous sarcoidosis, and the clinical experience with tetracycline derivatives has been mixed. That said, there are compelling reports of therapeutic benefit with both doxycycline and minocycline. Because neither of these agents is associated with the severe toxicity of cytotoxic drugs, they may serve as effective therapy in some patients. Pentoxifylline (400 mg three times daily) has been of use in a small number of reported cases of pulmonary sarcoidosis, but there are no reports on its use in patients with primarily cutaneous disease. Both ciclosporin and chlorambucil have been largely abandoned given their associated toxicity and disappointingly unreliable efficacy. Finally, laser therapy is a newer modality that may provide patients with a quick and non-invasive treatment option for cutaneous sarcoidosis.
Minocycline protects melanocytes against H2O2-inducedcell death via JNK and p38 MAPK pathways.
Int J Mol Med. 2008 Jul; 22(1): 9-16
Song X, Xu A, Pan W, Wallin B, Kivlin R, Lu S, Cao C, Bi Z, Wan Y
Vitiligo is an acquired and progressive disorder manifested by the selective destruction of melanocytes in the skin. An extremely high level of hydrogen peroxide (H2O2) in plasma as well as in lesional skin has been reported in vitiligo patients. High H2O2 level has been suggested to be responsible for the disappearance of melanocytes in vitiligo. JNK and p38 MAPK are strongly induced by oxidative stress and related to neuron loss in neurodegenerative disorders. Minocycline, an antibiotic possessing antioxidant activity, is capable of attenuating oxidative stress-induced neurotoxicity. To investigate whether minocycline rescues melanocytes from H2O2-induced apoptosis, cultured mouse melanocytes (B10BR) were treated with H2O2 in the presence or absence of minocycline. Our data showed that H2O2 decreases cell viability in a concentration-dependent manner which is attenuated by minocycline. Also, H2O2 treatment activates JNK and p38 MAPK, and executive caspase 3 in B10BR cells. Minocycline significantly inhibits H2O2-induced activation of JNK, p38 MAPK and caspase 3. Collectively, we concluded that minocycline protects melanocytes against H2O2-induced apoptosis in vitro. Its protective effect is associated with the inhibition of JNK and p38 MAPK. Our findings suggest that minocycline, a clinically well-tolerated, safe antibiotic, may be used to prevent melanocyte loss in the early stage of vitiligo.
Pilot study of minocycline in relapsing-remitting multiple sclerosis.
Can J Neurol Sci. 2008 May; 35(2): 185-91
Zhang Y, Metz LM, Yong VW, Bell RB, Yeung M, Patry DG, Mitchell JR
BACKGROUND: Current multiple sclerosis (MS) treatment is only partially effective and not all patients respond well. The goal in this study was to evaluate minocycline for its safety, tolerability, and MRI impact as a potential therapy over 36 months after a three month run-in in ten relapsing-remitting (RR) MS patients. METHODS: Clinical assessments were at three month intervals until six months, then at six month intervals. Three Tesla MRI was performed monthly during the run-in and first six months of treatment, then at 12, 24, and 36 months. RESULTS: Treatment was safe and well tolerated. Annualized relapse rate was 1.2 during the run-in and 0.25 during treatment. The proportion of active scans was lower during the first six months of treatment (5.6%, p < 0.001) and during the extension (8.7%, p = 0.002) than during the run-in (47.5%). Consistent with these outcomes, mean T2 lesion volume remained stable over three years and percent brain volume change was reduced during year three (-0.37%) of minocycline treatment. CONCLUSIONS: This trial is limited by small sample and no control group but suggests that minocycline is safe and potentially beneficial in RRMS. This supports further investigation of its efficacy.
Antimicrob Agents Chemother. 2008 Jun 23;
Dicenzo R, Peterson DR, Cruttenden K, Mariuz P, Rezk NL, Hochreiter J, Gelbard H, Schifitto G
Background: Minocycline and valproic acid are potential adjuvant therapies for the treatment of HIV-associated cognitive impairment. The purpose of the study was to determine if minocycline alone or in combination with valproic acid affected atazanavir plasma concentrations. Methods: Twelve adult HIV-infected subjects whose regimen included atazanavir/ritonavir 300/100 mg daily for at least 4 weeks were enrolled. Each subject received atazanavir/ritonavir on Day 1, atazanavir/ritonavir plus minocycline 100 mg twice daily on Days 2 - 15, and atazanavir/ritonavir plus minocycline 100 mg twice daily and valproic acid 250 mg twice daily on Days 16 - 30 with meals. Subjects had 11 plasma samples drawn over a dosing interval on Days 1, 15, and 30. Results: Minocycline and valproic acid coadministration was well tolerated in all 12 subjects (6 male; mean (SD) age = 43.1 (8.2) years). The geometric mean ratio (GMR (95% CI)) for atazanvir AUC24h, Cmin and Cmax with and without minocycline was 0.67 (0.50 - 0.90), 0.50 (0.28 - 0.89) and 0.75 (0.58 - 0.95), respectively. Similar decreases in atazanavir exposure were seen after the addition of valproic acid. The GMR (95% CI) for atazanavir AUC24h, Cmin and Cmax with and without minocycline plus valproic acid was 0.68 (0.43 - 1.06), 0.50 (0.24 - 1.06) and 0.66 (0.41 - 1.06), respectively. Neither minocycline nor minocycline plus valproic acid coadministration appeared to influence the plasma concentrations of ritonavir (p > 0.2). Conclusions: Minocycline coadministration resulted in decreased atazanavir exposure and there was no evidence that the addition of valproic acid mediated this effect.
Biologically based treatment of immature permanent teeth with pulpal necrosis: a case series.
J Endod. 2008 Jul; 34(7): 876-87
Jung IY, Lee SJ, Hargreaves KM
This case series reports the outcomes of 8 patients (ages 9-14 years) who presented with 9 immature permanent teeth with pulpal necrosis and apical periodontitis. During treatment, 5 of the teeth were found to have at least some residual vital tissue remaining in the root canal systems. After NaOCl irrigation and medication with ciprofloxacin, metronidazole, and minocycline, these teeth were sealed with mineral trioxide aggregate and restored. The other group of 4 teeth had no evidence of any residual vital pulp tissue. This second group of teeth was treated with NaOCl irrigation and medicated with ciprofloxacin, metronidazole, and minocycline followed by a revascularization procedure adopted from the trauma literature (bleeding evoked to form an intracanal blood clot). In both groups of patients, there was evidence of satisfactory postoperative clinical outcomes (1-5 years); the patients were asymptomatic, no sinus tracts were evident, apical periodontitis was resolved, and there was radiographic evidence of continuing thickness of dentinal walls, apical closure, or increased root length.