Volatile products and new polymer structures formed on Co-60 gamma-radiolysis of poly(lactic acid) and poly(glycolic acid)

A gas product analysis has been conducted on gamma-irradiated samples of poly(lactic acid) (PLA) and poly(glycolic acid) (PGA) by means of gas chromatography. The major volatile products have been identified to be CO, CO2, CH4 and C2H6 for PLA, and CO and CO2 for PGA. In addition, the yield of evolved gases for PLA has been found to be 1.81 for CO2, 0.98 for CO, 0.026 for CH4 and 0.012 for C2H6; and that for PGA to be 1.70 for CO2 and 0.42 for CO. The new chain ends formed due to gamma-induced bond cleavage in PLA have been assigned to CH3-CH2-CO-O- and CH3-CH2-O-CO-, and the G values for formation of these chain ends were found to be 1.9 and 0.6, respectively. The G value for chain scission reported previously of 2.3 is comparable with that for the formation of the propanoic acid end group. (C) 1997 Elsevier Science Limited.

The Swiss heroin trials: testing alternative approaches

Over half a million heroin misusers receive oral methadone maintenance treatment world-wide1 but the maintenance prescription of injectable opioid drugs, like heroin, remains controversial. In 1992 Switzerland began a large scale evaluation of heroin and other injectable opiate prescribing that eventually involved 1035 misusers. 2 3 The results of the evaluation have recently been reported.4 These show that it was feasible to provide heroin by intravenous injection at a clinic, up to three times a day, for seven days a week. This was done while maintaining good drug control, good order, client safety, and staff morale. Patients were stabilised on 500 to 600 mg heroin daily without evidence of increasing tolerance. Retention in treatment was 89% at six months and 69% at 18 months.4 The self reported use of non-prescribed heroin fell signifianctly, but other drug use was minimally affected. The death rate was 1% per year, and there were no deaths from overdose among participants . . . [Full text of this article]

Absorption of sunscreens across human skin: an evaluation of commercial products for children and adults

Aims Topical sunscreens are routinely applied to the skin by a large percentage of the population. This study assessed the extent of absorption of a number of common chemical sunscreen agents into and through human skin following application of commercially available products. Methods Sunscreen products were applied to excised human epidermis in Franz diffusion cells with the amount penetrating into and across the epidermis assessed by h.p.l.c. for 8 h following application. Results All sunscreen agents investigated penetrated into the skin (0.25 g m(-2) or 14% of applied dose), but only benzophenone-3 passed through the skin in significant amounts (0.08 g m(-2) or 10% of the applied dose). With one exception, suncreen agents in corresponding products marketed for adults and children had similar skin penetration profiles. Conclusions Whilst limited absorption across the skin was observed for the majority of the sunscreens tested, benzophenone-3 demonstrated sufficiently high penetration to warrant further investigation of its continued application.

Reverse transcription of a naturally occurring nonretroviral RNA produces a precise deletion in the majority of its cDNA products

A precise, reproducible deletion made during in vitro reverse transcription of RNA2 from the icosahedral positive-stranded Helicoverpa armigera stunt virus (Tetraviridae) is described. The deletion, located between two hexamer repeats, is a 50-base sequence that includes one copy of the hexamer repeat. Only the Moloney murine leukemia virus reverse transcriptase and its derivative Superscript I, carrying a deletion of the carboxy-terminal RNase H region, showed this response, indicating a template-switching mechanism different from one proposed that involves a RNase H-dependent strand transfer, Superscript II, however, which carries point mutations to reduce RNase H activity, does not cause a deletion. A possible mechanism involves the enzyme pausing at the 3' side of a stem-loop structure and the 3' end of the nascent DNA strand separating from the template and reannealing to the upstream hexamer repeat.

High HIV incidence and prevalence among young women in rural South Africa: Developing a cohort for intervention trials

Objective: To measure prevalence and model incidence of HIV infection. Setting: 2013 consecutive pregnant women attending public sector antenatal clinics in 1997 in Hlabisa health district, South Africa. Historical seroprevalence data, 1992-1995. Methods: Serum remaining from syphilis testing was tested anonymously for antibodies to HIV to determine seroprevalence. Two models, allowing for differential mortality between HIV-positive and HIV-negative people, were used. The first used serial seroprevalence data to estimate trends in annual incidence. The second, a maximum likelihood model, took account of changing force of infection and age-dependent risk of infection, to estimate age-specific HIV incidence in 1997. Multiple logistic regression provided adjusted odds ratios (OR) for risk factors for prevalent HIV infection. Results: Estimated annual HIV incidence increased from 4% in 1992/1993 to 10% in 1996/1997. In 1997, highest age-specific incidence was 16% among women aged between 20 and 24 years. in 1997, overall prevalence was 26% (95% confidence interval [CI], 24%-28%) and at 34% was highest among women aged between 20 and 24 years. Young age (<30 years; odds ratio [OR], 2.1; p = .001), unmarried status (OR 2.2; p = .001) and living in less remote parts of the district (OR 1.5; p = .002) were associated with HIV prevalence in univariate analysis. Associations were less strong in multivariate analysis. Partner's migration status was not associated with HIV infection. Substantial heterogeneity of HIV prevalence by clinic was observed (range 17%-31%; test for trend, p = .001). Conclusions: This community is experiencing an explosive HIV epidemic. Young, single women in the more developed parts of the district would form an appropriate cohort to test, and benefit from, interventions such as vaginal microbicides and HIV vaccines.

Preliminary experiences with a single-patient trials service in general practice

Objective: To pilot a single-patient trials (SPTs) service in general practice, designed to improve decision-making about long-term medications for chronic conditions. Design: 12-week within-patient, randomised, double-blind, placebo-controlled, crossover comparison of ibuprofen with paracetamol for osteoarthritis, involving three pairs of two-week treatment periods for each participating patient. Setting and patients: Patients attending an academic general practice with a clinical diagnosis of osteoarthritis, with pain of at least a month's duration severe enough to warrant consideration of long-term non-steroidal anti-inflammatory drug (NSAID) use. Main outcome measures: Pain and stiffness; measures of overall arthritis compared with previous fortnight; preference for NSAID at the end of each two-week treatment period; use of escape analgesia; side effects; and management changes as a result of the SPTs. Results: Eight of 14 patients completed SPTs. One was a clear responder to NSAIDs, five were non-responders, and two were indefinite. Of the five who were using NSAIDs before the SPT, two continued and three ceased using them. Clinically useful information assisted decision-making for all eight participants. Medication management changed for six. Conclusions: Single-patient trials can be successfully implemented in general practice and might be a valuable method for GPs to identify patients who respond to medication for chronic stable conditions such as osteoarthritis, in which individual response to medication is variable.

Identification of physiologically functional peptides in dairy products

A wide range of peptides produced from milk proteins have been demonstrated to produce a physiological response in model systems. These peptides may be released from intact proteins in the gastrointestinal tract by proteolytic digestion, but are also present in fermented products such as cheese and yogurt, as a result of the action of inherent proteases, such as plasmin, and/or bacterial proteases released by the starter culture. This study investigated the presence of peptides, previously reported to have bioactive properties, in commercially available yogurts and cheeses.

Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: systematic review and meta-analysis of randomised controlled trials including more than 5000 women

We aimed to determine the effectiveness of the vaginally administered spermicide nonoxynol-9 (N-9) among women for the prevention of HIV and other sexually transmitted infections (STIs), We did a systematic review of randomised controlled trials, Nine such trials including 5096 women, predominantly sex workers, comparing N-9 with placebo or no treatment, were included. Primary outcomes were new HIV infection, new episodes of various STIs, and genital lesions. Five trials included HIV and nine included STI outcomes, and all but one (2% of the data) contributed to the meta-analysis. Overall, relative risks of HIV infection (1.12, 95% confidence interval 0.88-1.42), gonorrhoea (0.91, 0.67-1.24), chlamyclia (0.88, 0.77-1.01), cervical infection (1.01, 0.84-1-22), trichomoniasis (0.84, 0.69-1.02), bacterial vaginosis (0.88, 0.74-1.04) and candidiasis (0.97, 0.84-1.12) were not significantly different in the N-9 and placebo or no treatment groups. Genital lesions were more common in the N-9 group (1.18, 1.02-1.36). Our review has found no statistically significant reduction in risk of HIV and STIs, and the confidence intervals indicate that any protection that may exist is likely to be very small. There is some evidence of harm through genital lesions. N-9 cannot be recommended for HIV and STI prevention.

Efficacy of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy for ovarian cancer

Transfer of the herpes simplex virus type I thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. Effective gene therapy,, depends on the efficient transfer and specific targeting of therapeutic genes and their protein products to target cells. The purpose of this study was to investigate the anti-tumor effect of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy in animal models. Mouse models were generated with intraperitoneal injection of human epithelial ovarian cancer cells 3AO, which are MUC1-positive. HTV-1-based lentiviral vectors carrying VP22-TK or scFv-VP22-TK were prepared. The animals were injected intraperitoneally with lentivirus containing scFv-VP22-TK, VP22-TK followed by GCV treatment. Combined treatment of lentivirus-expressed scFv-VP22-TK or VP22-TK with GCV inhibited the proliferation and prolonged survival times compared with the control vector. The survival time of animals treated with scFv-VP22-TK/GCV was significantly longer than that of animals treated with VP22-TK/GCV (p = 0.006). Conclusion: Our results suggest that MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy can efficiently inhibit ovarian tumor growth and increase survival in a nude mouse model of ovarian carcinoma. These data support the development of this method for human clinical trials.