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Therapeutic Arsenal (therapeutic + arsenal)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury

JOURNAL OF NEUROCHEMISTRY, Issue 5 2006
Barry W. Festoff
Abstract Minocycline, a clinically used tetracycline for over 40 years, crosses the blood,brain barrier and prevents caspase up-regulation. It reduces apoptosis in mouse models of Huntington's disease and familial amyotrophic lateral sclerosis (ALS) and is in clinical trial for sporadic ALS. Because apoptosis also occurs after brain and spinal cord (SCI) injury, its prevention may be useful in improving recovery. We analyzed minocycline's neuroprotective effects over 28 days following contusion SCI and found significant functional recovery compared to tetracycline. Histology, immunocytochemistry, and image analysis indicated statistically significant tissue sparing, reduced apoptosis and microgliosis, and less activated caspase-3 and substrate cleavage. Since our original report in abstract form, others have published both positive and negative effects of minocycline in various rodent models of SCI and with various routes of administration. We have since found decreased tumor necrosis factor-,, as well as caspase-3 mRNA expression, as possible mechanisms of action for minocycline's ameliorative action. These results support reports that modulating apoptosis, caspases, and microglia provide promising therapeutic targets for prevention and/or limiting the degree of functional loss after CNS trauma. Minocycline, and more potent chemically synthesized tetracyclines, may find a place in the therapeutic arsenal to promote recovery early after SCI in humans. [source]

Review article: investigational agents for chronic hepatitis C

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009
A. J. V. THOMPSON
Summary Background, The need for effective treatment for chronic hepatitis C infection has driven the development of novel antiviral agents that target specific steps in the viral replication cycle. Aim, To evaluate the current literature concerning investigational agents for chronic hepatitis C virus infection. Methods, Resources used included PubMed, conference proceedings from the American and European Liver Associations' meetings 2005,2008 and the National Institute of Health's clinical trials website (http://www.clinicaltrials.gov). The focus was restricted to investigational agents that have progressed beyond preclinical development. Results, Over 50 investigational agents for chronic hepatitis C infection are currently in clinical development. Specifically targeted anti-viral therapy for HCV (STAT-C) shows great promise with NS3/4a protease inhibitors now entering phase 3 programmes. New interferon-, and ribavirin formulations aim to optimize anti-viral efficacy yet limit toxicity. Other candidates include novel immunomodulators and therapeutic vaccines. Conclusions, A new era of therapy for chronic hepatitis C beckons, promising increased cure rates with shortened duration of therapy. However, the era will not be without challenges including viral resistance, drug toxicity and the need to optimize combination therapy in the face of a rapidly evolving therapeutic arsenal. [source]

Safety and efficacy of rituximab in systemic lupus erythematosus: Results from 136 patients from the French autoimmunity and rituximab registry

ARTHRITIS & RHEUMATISM, Issue 8 2010
Benjamin Terrier
Objective A number of open-label studies have suggested the potential benefit of rituximab (RTX) in systemic lupus erythematosus (SLE). However, in 2 recent randomized controlled trials (RCTs) of RTX, the primary end points were not met. We undertook this study to evaluate the safety and efficacy of RTX in off-trial patients with SLE seen in regular clinical practice. Methods We analyzed prospective data from the French AutoImmunity and Rituximab (AIR) registry, which includes data on patients with autoimmune disorders treated with RTX. Results One hundred thirty-six patients received treatment for SLE. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) was 11.3 ± 8.9 at baseline. Severe infections were noted in 12 patients (9%), corresponding to a rate of 6.6/100 patient-years. Most severe infections occurred within the first 3 months after the last RTX infusion. Five patients died, due to severe infection (n = 3) or refractory autoimmune disease (n = 2). Overall response was observed in 80 of 113 patients (71%) by the SELENA,SLEDAI assessment. Efficacy did not differ significantly between patients receiving RTX monotherapy and those receiving concomitant immunosuppressive agents (who had higher baseline disease activity). Articular, cutaneous, renal, and hematologic improvements were noted in 72%, 70%, 74%, and 88% of patients, respectively. Among responders, 41% experienced a relapse of disease, with a response in 91% after retreatment with RTX. Conclusion Data from the AIR registry show a satisfactory tolerance profile and clinical efficacy of RTX in patients with SLE. The contrasting results with those from recent RCTs leave open the question of the therapeutic use of RTX in SLE. Additional controlled studies with new designs are needed to define the place of RTX in the therapeutic arsenal for SLE. [source]

Secondary delusional parasitosis treated with paliperidone

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2009
R. W. Freudenmann
Summary Second-generation antipsychotics (SGA) are increasingly used in primary and secondary delusional parasitosis (DP) because of their better overall tolerability compared with first-generation antipsychotics (FGA) such as pimozide. Controlled clinical trials with antipsychotics in DP are lacking, owing to difficulties in obtaining informed consent and in securing adherence to a study protocol by patients with DP. We present the case of an 88-year-old man with a 12-year history of DP secondary to leucoencephalopathy. After 9 days of an age-adapted dose of paliperidone, the patient no longer experienced the presence of vermin on his skin and stopped showering at night to get rid off of them. Paliperidone was well tolerated. At follow-up after 2 weeks, the DP was still remitted. Paliperidone appears to expand the therapeutic arsenal in treating DP with modern SGAs; however, this finding needs to be replicated. [source]