Clastogenic effect of fenfluramine in mice bone marrow cells in vivo

Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo.     

Impact of nutritional status on peritonitis in CAPD patients.

OBJECTIVE: To determine the impact of nutritional status on peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) in a developing country. METHODS: 56 patients with end-stage renal disease on CAPD were randomly selected for this study. These patients were assessed for nutritional status and peritonitis episodes. Nutritional parameters were assessed by anthropometry, diet, body mass index (BMI), Nutritional Risk Index (NRI), serum albumin level, and Subjective Global Assessment (SGA). Based on SGA, patients were categorized into either group 1 (malnutrition, n = 31) or group 2 (normal nutritional status, n = 25). Peritonitis was considered the primary outcome and was compared between the two groups. RESULTS: Demographic profiles, Kt/V, creatinine clearance, and mean follow-up of the two groups were similar. Number of peritonitis episodes was significantly higher in patients with malnutrition (25/31) compared to patients with normal nutritional status (4/25) (p = 0.001). Mean peritonitis rate per patient per year was also significantly higher in patients with malnutrition (0.99 +/- 1.07) compared to patients with normal nutritional status (0.18 +/- 0.42) (p = 0.007). On univariate analysis, malnutrition based on SGA (p = 0.009), NRI (p = 0.02), serum albumin level (p = 0.005), and calorie intake (p = 0.006) was a significant predictor of peritonitis. On multivariate Cox regression analysis, only SGA (p = 0.001, odds ratio 0.08, 95% confidence interval 0.02-0.36) was found to be a significant predictor of peritonitis. On general linear model, the observed power of prediction of peritonitis was 0.96 based on SGA. On Kaplan-Meier survival analysis, peritonitis-free survival in patients with normal nutrition (42 months) was significantly higher compared to patients with malnutrition (21 months) based on SGA (log rank p = 0.003). CONCLUSION: We conclude that peritonitis rate is high in patients with malnutrition and that malnutrition indices, especially SGA, can predict the peritonitis rate in CAPD patients.     

Effect of heterophil depletion by 5-fluorouracil on infectious bronchitis virus infection in chickens.

An anti-tumour drug, 5-fluorouracil (5 FU) was used to deplete heterophils in 11-day-old white leghorn chickens. The reduction in heterophil numbers was monitored by total and differential white cell counts in the peripheral blood. Three days after injection of 5 FU, when the heterophil numbers were significantly reduced, chickens were infected with the Massachusetts strain of infectious bronchitis virus (IBV). Following infection, although the numbers of birds exhibiting clinical signs (nasal exudate) were significantly higher in the 5 FU treated group, the consistency of the nasal exudate was characteristically thin and watery. No significant differences were seen in the virus titres in trachea, lung and kidney between normal and heteropaenic chickens infected with IBV. However, the epithelial cell damage in the tracheal sections was less in the heterophil-depleted chickens.     

Plasma cell granuloma of jaw A case report

A 65 year old Punjabi male presented with an exophytic lesion, 3 Cm. in diameter, which was pedunculated, on the attached gingiva. It was situated on the right side, near the motars. On histological examination, it was diagnosed as plasma cell granuloma.     

Natural killer cells and reproductive failure--theory, practice and prejudice

The relationship between peripheral blood natural killer (NK) cells and reproductive failure is one of the most controversial areas in reproductive medicine. Amidst much publicity, peripheral blood NK cell testing is being promoted as a useful diagnostic test to guide the initiation of a variety of immunosuppressive therapies amongst patients with either recurrent miscarriage or infertility. We contend (i) that at present there is no scientific basis for the introduction of NK cell testing into routine clinical practice, and (ii) that the use of immunosuppressant agents based on the results of such testing may potentially be harmful.     

Rapid particle agglutination test for human immunodeficiency virus: hospital-based evaluation

The performance of a rapid particle agglutination test for human immunodeficiency virus (HIV) (Capillus HIV type 1 [HIV-1]/HIV-2) on hospital samples is compared with enzyme-linked immunosorbent assays. The test had a sensitivity and specificity of 99 and 98.9%, respectively. In addition, the test was reactive on plasma samples from all individuals infected with HIV-1 subtype C. This test can safely be used for voluntary counseling and testing in India.     

CD1d deficiency exacerbates inflammatory dermatitis in MRL-lpr/lpr mice

Mechanisms responsible for the development of autoimmune skin disease in humans and animal models with lupus remain poorly understood. In this study, we have investigated the role of CD1d, an antigen-presenting molecule known to activate natural killer T cells, in the development of inflammatory dermatitis in lupus-susceptible MRL-lpr/lpr mice. In particular, we have established MRL-lpr/lpr mice carrying a germ-line deletion of the CD1d genes. We demonstrate that CD1d-deficient MRL-lpr/lpr mice, as compared with wild-type littermates, have more frequent and more severe skin disease, with increased local infiltration with mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d-deficient MRL-lpr/lpr mice had increased prevalence of CD4(+) T cells in the spleen and liver and of TCR alpha beta (+)B220(+) cells in lymph nodes. Furthermore, CD1d deficiency was associated with decreased T cell production of type 2 cytokines and increased or unchanged type 1 cytokines. These findings indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the mechanisms by which CD1d deficiency results in splenic T cell expansion and cytokine alterations, with increased dermal infiltration of dendritic cells and lymphocytes in MRL-lpr/lpr mice, will have implications for the pathogenesis of inflammatory skin diseases.     

Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis.

One strategy for improving resistance to opportunistic pathogens is to determine host cellular responses during the invasion process and upregulate those responses that are relevant to host defense mechanisms. Within this context, we have shown previously that invasion of endothelial cells by Candida albicans in vitro causes increased production of prostaglandins. As a prerequisite for modulating endothelial cell prostaglandin production, we now characterize the mechanisms through which this process occurs. Endothelial cell invasion by C. albicans appeared to stimulate the conversion of arachidonic acid into prostaglandins by upregulating the synthesis of endothelial cell cyclooxygenase and increasing the activity of the endothelial cell phospholipase. The enhanced activities of these two enzymes were independent of calphostin C-sensitive protein kinase C and resulted in the increased production and extracellular secretion of prostaglandin I2 (PGI2), PGF2 alpha, and PGE2. The secretion of these prostaglandins had no effect on the amount of endothelial cell injury induced by C. albicans. The role of the increased prostaglandin secretion by endothelial cells is likely related to modulation of the leukocyte response at the candida-leukocyte-endothelial cell interface.     

Creating a death register for general practice.

General practitioners complete approximately 26% of death certificates themselves but have considerable difficulty obtaining prompt and accurate information about their other patients who die. A random survey of district health authorities in England revealed that all were able to compile death lists but none included general practitioner details. This paper reviews the flow of information on patient deaths and describes a project to assess the feasibility of providing Newcastle general practitioners with comprehensive death registers. With the collaboration of the family health services authority and the district health authority, and with data from the regional perinatal mortality survey the creation each week of complete lists of patient deaths, broken down by general practitioner, is feasible. Death registers allow general practitioners to undertake audit of the quality of death certification and of the care of the recently deceased, and to improve the continuing care of the bereaved.     

Reciprocal T-B determinant spreading develops spontaneously in murine lupus: implications for pathogenesis

Summary: Recent work from several laboratories has shown that, in contrast to the widely held notion that one autoimmune disease is caused by one or a few related autoantigenic determinants, autoimmunity is fundamentally a continuously evolving process. The autoimmune responses shift, drift and diversify with time not only to other determinants in the original antigen but also to other antigens. We have described a form of determinant spreading - reciprocal T-B determinant spreading–where the induction of first T cells by peptides from an autoantibody molecule could lead to help provided to a variety of B cells displaying a cross-reactive version of the original determinant. The response spreads in this way by reciprocal T-B stimulation until large cohorts of T and B cells have expanded. Such spontaneous expansion must be important in clinical disease, since tolerance induction to a limited set of T-cell determinant peptides derived from an anti-DNA antibody VH region delayed the appearance of IgG anti-dsDNA antibodies and onset of lupus nephritis in the NZB/NZW Fl mouse model of systemic lupus erythematosus. Understanding the diversification patterns in autoimmune responses has enormous implications in developing peptide-targeted therapies.