WR1065 mitigates AZT-ddI-induced mutagenesis and inhibits viral replication

The success of nucleoside reverse transcriptase inhibitors (NRTIs) in treating HIV-1 infection and reducing mother-to-child transmission of the virus during pregnancy is accompanied by evidence that NRTIs cause long-term health risks for cancer and mitochondrial disease. Thus, agents that mitigate toxicities of the current combination drug therapies are needed. Previous work had shown that the NRTI-drug pair zidovudine (AZT)–didanosine (ddI) was highly cytotoxic and mutagenic; thus, we conducted preliminary studies to investigate the ability of the active moiety of amifostine, WR1065, to protect against the deleterious effects of this NRTI-drug pair. In TK6 cells exposed to 100 μM AZT-ddI (equimolar) for 3 days with or without 150 μM WR1065, WR1065 enhanced long-term cell survival and significantly reduced AZT-ddI-induced mutations. Follow-up studies were conducted to determine if coexposure to AZT and WR1065 abrogated the antiretroviral efficacy of AZT. In human T-cell blasts infected with HIV-1 in culture, inhibition of p24 protein production was observed in cells treated with 10 μM AZT in the absence or presence of 5–1,000 μM WR1065. Surprisingly, WR1065 alone exhibited dose-related inhibition of HIV-1 p24 protein production. WR1065 also had antiviral efficacy against three species of adenovirus and influenza A and B. Intracellular levels of unbound WR1065 were measured following in vitro/in vivo drug exposure. These pilot study results indicate that WR1065, at low intracellular levels, has cytoprotective and antimutagenic activities against the most mutagenic pair of NRTIs and has broad spectrum anti-viral effects. These findings suggest that the activities have a possible common mode of action that merits further investigation

Recent Surgical and Medical Advances in the Treatment of Dupuytren’s Disease - A Systematic Review of the Literature

Dupuytren’s disease (DD) is a type of fibromatosis which progressively results in the shortening and thickening of the fibrous tissue of the palmar fascia. This condition which predominantly affects white-northern Europeans has been identified since 1614. DD can affect certain activities of daily living such as face washing, combing hair and putting hand in a glove. The origin of Dupuytren’s contracture is still unknown, but there are a number of treatments that doctors have come across throughout the years. Historically surgery has been the mainstay treatment for DD but not the only one. The objective is to make a structured review of the most recent advances in treatment of DD including the surgical and medical interventions. We have looked at the most relevant published articles regarding the various treatment options for DD. This review has taken 55 articles into consideration which have met the inclusion criteria. The most recent treatments used are multi-needle aponeurotomy, extensive percutaneous aponeurotomy and lipografting, injecting collagenase Clostridium histolyticum, INF-gamma and shockwave therapy as well as radiotherapy. Each of these treatments has certain advantages and drawbacks and cannot be used for every patient. In order to prevent this condition, spending more time and money in the topic is required to reach better and more consistent treatments and ultimately to eradicate this disease