Effect of Freezer Programs on Real-Time Storage Results of Dissolution Profiles

Carstensen and Rhodes¹ have suggested that when, in stability programs, assays cannot be performed immediately after the protocol-designated storage time, then freezing them until such a time when assays can be performed would be a reasonable manner to retain the protocol schedule. They caution, however, that such a procedure may not be valid for dissolution data. The article to follow deals with real-time data showing that such a process is feasible for Nalidixic Acid tablets (and presumably for other tablets as well), and that, furthermore, the dissolution pattern would seem to be “frozen” as well.     

Influence of labour on epidermal growth factor receptor distribution of the human chorion at term gestation

Ten patients with biopsy verified chronic hepatitis C virus (HCV) infection were treated with oral ribavirin at a dose of 1,000-1,200 mg per day in two divided doses for 12 weeks. Serum alanine aminotransferase (ALT) levels and hepatitis C viral ribonucleic acid (RNA) levels in serum were followed prior to, during, and 12 weeks posttreatment. ALT levels decreased significantly in all patients during therapy from a mean level of 3.21 mukat/l (range 1.22 to 7.79) before, to 1.25 mukat/l (range 0.78 to 2.04) at the end of treatment (P < 0.005). Hereafter, relapse to pretreatment levels was seen within 12 weeks after treatment stop. The hepatitis C viral RNA levels decreased from a mean 10 log titer of 4.1 (range 1-6) before treatment to 3.4 (range 1-5) at treatment stop. Five patients did not change their HCV RNA titers during treatment. Twelve weeks posttreatment only 3 patients had lower titers than prior to treatment. We conclude that oral ribavirin seems to reduce the viral load, at least temporarily, in some patients with chronic viremic HCV infection. Further studies are needed to evaluate fully the effect of oral ribavirin on chronic HCV infection.     

Increased concentrations of octachlorodibenzo-p-dioxin in cases with breast cancer--results from a case-control study

Organochlorines are persistent and highly lipophilic environmental contaminants which bioaccumulate in the food chain. Some of these chemicals, 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and polychlorinated biphenyls (PCBs), have been suggested to be of significance in the aetiology of breast cancer. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an anti-oestrogen in animal studies and should be thus lower the risk of breast cancer. The other isomers of polychlorinated dibenzo-p-dioxins (PCDDs) or the chemically related polychlorinated dibenzofurans (PCDFs) have not been tested regarding carcinogenesis of the breast. The purpose of this study was to investigate whether PCDDs or PCDFs influence the risk for breast cancer. Consecutive patients who underwent surgery for a breast disease between 1993 and 1995 were recruited for the study. Cases were 22 patients with infiltrative breast cancer and controls were 19 patients operated for a benign breast disease during the same time period. Approximately 10 g of breast tissue free from tumour was taken from the specimen and frozen until analysis. Fat was extracted, cleaned and analysed with a high-resolution gas chromatograph coupled to a high-resolution mass spectrometer. Median concentrations of octachlorinated dibenzo-p-dioxin (OCDD) were 598 (170-14,880) and 396 (103-1,847) pg/g lipid in the cases and in the controls, respectively. In a multivariate logistic regression analysis controlling for other risk factors for breast cancer increased odds ratio (OR) was obtained for OCDD: 401-1000 pg/g lipid yielded OR 3.8, 95% confidence interval (CI) 0.4-39, > 1000 pg/g lipid gave OR 5.2, CI 0.4-72. When the lipid OCDD variable was examined as a continuous risk factor there was a 1.09 (9%), CI 0.95-1.25, increase in the adjusted OR for breast cancer per 100 unit (pg/g lipid) increase in OCDD. No differences were found between cases and controls for the other six tested PCDDs. Mean concentration of TCDD was in the cases 3.6 (1.0-7.9) and in the controls 3.3 (1.1-6.3) pg/g lipid. For PCDFs no significant differences were found between cases and controls. The results were not changed if oestrogen or progesterone receptor status, S-phase fraction and DNA ploidy were considered. Breast tissue concentration of OCDD was increased in cancer patients, whereas the concentrations of other PCDDs and PCDFs were equal in cases and controls.     

Deformation and fracture of glass bead/ CTBN-rubber/epoxy composites

Carboxyl-terminated butadiene-acrylonitrile-rubber decreases modulus and yield stress of the studied epoxy but increases fracture toughness. The addition of glass bead compensates for the loss in modulus but has little effect on yield stress. However, it significantly contributes to the fracture toughness by providing additional mechanisms for toughening of both the unmodified and rubber-modified epoxy. For the toughened epoxies studied, fracture surfaces gave only limited information on fracture mechanisms since significant energy absorption also occurs in the material below the fracture surface. Suggestions for suitable material compositions for fiber composite matrices are given.