High-performance liquid chromatographic determination of bisacodyl in pharmaceutical dosage forms marketed in Australia

HPLC methods have been developed for the assay of bisacodyl in various pharmaceutical forms. The extraction procedures are simple and the HPLC conditions separate bisacodyl from its degradation products. The chromatography was performed using a Merck LiChrospher RP-select B column, a mobile phase of 55% acetonitrile/45% 0.05 M KH2PO4 and detection by UV at 214 nm.     

Mesenteric vasculopathy in intestinal tuberculosis

BACKGROUND: Involvement of mesenteric vessels in intestinal tuberculosis and its role in the pathogenesis of the intestinal changes have not been studied histologically. AIM: To study mesenteric vessels in patients undergoing surgery for complications of intestinal tuberculosis. METHODS: Resected intestinal specimens from 68 patients presenting with intestinal perforation and intestinal obstruction were examined; involvement of the major mesenteric vessels was evaluated. RESULTS: Granulomas were seen in the vessel wall in one case and near the vessel wall in 11 cases, intraluminal thrombi were seen in 23 cases, and subintimal fibrosis in nine cases. Perivascular cuffing was seen in intramural and subserosal vessels in ten cases. CONCLUSIONS: Changes in the vessel wall may lead to gut ischemia, which may contribute to the development of strictures and stercoral perforation in intestinal tuberculosis.     

Cryoprecipitate prepared from plasma virally inactivated by the solvent detergent method

The newly discovered peptide nociceptin/orphanin FQ has been found to increase reactivity to pain and to influence locomotor activity after intracerebroventricular administration. This study investigated the possible role of hippocampal nociceptin/orphanin FQ in spatial learning and in spontaneous locomotion. Male rats were trained in the Morris water task after microinjection of 10 nmol nociceptin/orphanin FQ or artificial cerebrospinal fluid (as control) into the CA3 region of the dorsal hippocampus. Nociceptin/orphanin FQ was found to severely impair spatial learning without interfering with swimming performance. Intrahippocampal injection of nociceptin/ orphanin FQ markedly decreased exploratory locomotor activity including vertical movements (rearing). The data suggest that nociceptin/orphanin FQ is a potent modulator of synaptic plasticity within the hippocampus.     

Ganciclovir induces reproductive hazards in male rats after short-term exposure

1. The effect of short-term treatment of ganciclovir on male reproduction in adult rats was studied. The animals were treated subcutaneously with either a single dose of 60 mg/kg daily for 5 days (Gan5day) or with 100 mg/kg administered three times at 4 h-intervals (Gan1day). The effects were investigated every 2 weeks up to 8 weeks, followed by investigations 16 and 24 weeks after treatment to detect the potential of recovery. 2. Time to mating was significantly increased in Gan1day group. The pregnancy index and outcome were only decreased 8 weeks (Gan5day and Gan1day) or 16 weeks (Gan1day) after treatment. 3. The lowest values of sperm variables studied were registered 8 weeks after treatment: The number of spermatid was reduced up to 4% (Gan5day) or 2% (Gan1day) of control; the sperm number was 5% and 8% of control in Gan5day and Gan1day, respectively. Over 80% of sperm were abnormal in Gan5day group, and only few normal sperm was detected in Gan1day group. 4. Morphological investigation of testes revealed a clearcut time-dependency effect. Four weeks after treatment distinct alterations were located exclusively in the peripheral part of the tubuli which included fat inclusions, cell and pyknotic nuclear debris and swellings of Sertoli cells. The effect was reversible 24 weeks after treatment. 5. Ganciclovir induces testicular damage and affects sperm variables after short-term exposure. The intensity and degree of the hazards varied in between the time of investigation after treatment.     

Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion

Levels of allergen-specific IgE and IgE antibodies were determined in serum samples from 60 atopic and 11 normal dogs by means of commercially available ELISA test kits and a panel of 33 allergens. In the atopic population, IgE antibodies were most commonly identified with a specificity for Dermatophagoides farinae (78.3 per cent of affected dogs), D pteronyssinus (61.6 per cent), mould mix (25 per cent) and house dust (19 per cent), whereas the most frequently detected IgG antibodies had a specificity for D farinae (38.3 per cent), D pteronyssinus (33.3 per cent), mould mix (33.3 per cent), insect mix (16.6 per cent) and meadow fescue (16.6 per cent). The IgG subclass profile of allergen-specific antibodies was determined for five representative allergens from the panel. The IgG response to D farinae and D pteronyssinus was dominated by IgG4 antibodies, although lower levels of IgG2, and IgG3 and IgG1 D pteronyssinus antibodies were also detected. The IgG response to Timothy grass was predominantly within the IgG1 and IgG4 subclasses, IgG subclass selection in the response to mould mix and insect mix was broader, with relatively low level reactions from all four subclasses. The data suggest a degree of IgG subclass restriction in the humoral immune response of canine atopy which may be dependent upon the nature of the allergen.     

Immunohistochemical and morphological characterization of spontaneously occurring pheochromocytomas in the aging mouse

Pheochromocytomas in mice are rare tumors, and their expression of functional markers has not previously been assessed. In this study, 29 spontaneously occurring mouse pheochromocytomas were characterized morphologically and immunohistochemically to determine whether there are functional correlates to previously described morphological features and to provide a database for comparison with tumors that arise in genetically engineered animals. The tumors were derived from 28 mice 828-1,489 days old, of three genotypes. Considerable cytological and architectural polymorphism was observed both within and between tumors. Most of the tumor cells were comparable in size to normal chromaffin cells or were larger. Small basophilic cells, which are the predominant cell type in rat pheochromocytomas, were usually in the minority. All of the tumors and most of the cells within individual tumors expressed immunoreactive tyrosine hydroxylase (TH). The tumors were variably positive for phenylethanolamine-N-methyltransferase (PNMT) and chromogranin A (CGA). There did not appear to be a global association of specific cytological features with expression of TH, PNMT, or CGA, although cells of similar appearance often shared similar immunoreactivities within individual tumors. Small basophilic cells could be either PNMT-positive or PNMT-negative. The frequency, morphology, and immunophenotype of mouse pheochromocytomas suggest that the mouse may be more appropriate than the rat as a model for human adrenal medullary pathology. In addition, the expression of immunoreactive PNMT by mouse pheochromocytomas suggests that these tumors are a potential source of epinephrine-producing cell lines, for which adequate models currently do not exist.     

Rate of HIV-1 decline following antiretroviral therapy is related to viral load at baseline and drug regimen

OBJECTIVES AND DESIGN: The dynamics uf viral decline following the initiation of antiretroviral treatment were studied in 29 HIV-1-infected patients participating in a two-arm trial comparing immediate (group A: ritonavir, zidovudine and lamivudine) and delayed (group B: ritonavir supplemented by zidovudine and lamivudine on day 21) triple therapy. Parameters underlying viral dynamics were estimated using mathematical models tailored to these treatment protocols. RESULTS: The decline in plasma HIV-1 density between day 0 and 21 was steeper in group A (-2.27+/- 0.46 log10) than group B (-1.87+/-0.56 log10). In a subset of patients amenable to full mathematical analysis, a short-lived productively infected cell compartment (producing approximately 97% of total virions) decayed with a half-life of 1.0-2.5 days, whereas a long-lived infected cell compartment decayed with a half-life of 18.8-32.8 days. Estimates for the time for the elimination of virus from these two cell populations ranged from 474 to 802 days. The rate of loss of productively infected CD4+ T cells was positively correlated with baseline viral load in group A and in the combined dataset. CONCLUSIONS: These results suggest that HIV-infected cell populations may have a faster turnover in patients with higher viral loads due to higher infection rate parameters, higher rates of virus production, or lower virus clearance rates.