Monosialoganglioside GM1 inhibits neurotoxicity after hypothermic circulatory arrest

BACKGROUND/AIM: A herbal medicine, Sho-saiko-to (TJ-9), has recently been orally administered to patients with chronic liver disease in Japan and has been reported to inhibit the development of hepatocellular carcinoma. The aim of this study was to investigate whether TJ-9 has an inhibitory effect on the development of preneoplastic lesions and liver fibrosis in rats. METHODS: The effects of the TJ-9 were examined using the choline-deficient L-amino acid-defined (CDAA) diet-induced liver fibrosis model in 16-week-old male Wistar rats. RESULTS: TJ-9 (1% w/w) prevented fibrosis, as indicated by reduced hydroxyproline content in the liver and inhibition of the increase in a serum marker of fibrosis (hyaluronic acid), without reducing the increase in serum alanine aminotransferase and aspartate aminotransferase. TJ-9 also reduced the expression of type III procollagen alpha 1 mRNA in the liver, as well as the proliferation of myofibroblast-like cells (activated stellate cells, activated Ito cells). Furthermore, TJ-9 reduced the number of preneoplastic lesions, detected as enzyme-altered (glutathione S-transferase placental form-positive) lesions, in the liver. CONCLUSIONS: These results indicate that the herbal medicine Sho-saiko-to (TJ-9) prevents fibrosis as well as preneoplastic lesions, not by inhibiting hepatocyte cell death but by inhibiting the activation of stellate cells, which are considered to be the main collagen-producing cells, leading to a reduction in the development of preneoplastic lesions.     

Clinical predictors of HIV-1 infection among preschool children in Dar es Salaam, Tanzania

Seroprevalence of HIV-1 infection was determined in children aged between eighteen months and five years, attending maternal and child health (MCH) clinics in Dar es Salaam, Tanzania. A total of 889 children were eligible for the study, however seven children could not be enrolled because their mothers/guardians absconded and blood could not be drawn from 21 children due to refusal of mothers/guardians and from another 12 children due to technical reasons. Therefore, the participation rate was 95.5%. Of the 849 children screened, 14 (1.65%) were found to have IgG anti HIV-1 antibodies in their sera. The main clinical features found in children with symptomatic HIV-1 disease were weight loss, generalized lymphadenopathy, recurrent fevers, and prolonged diarrhoea. The utility of clinical features suggestive of HIV-1 infection (according to CDC classification) in identifying HIV-1 infection in children was evaluated and found to have high sensitivity (100%), specificity (96.9%) and negative predictive value (100%), but a low positive predictive value (35%). Marked variations in progression to symptomatic phase were noted, whereby some relatively young children had progressed to symptomatic phase (CDC class P-2A), while some older children were still in the asymptomatic stage (CDC class P-1 C). None of the symptomatic HIV-1 infected children presented with neurological disease, severe opportunistic infections, or malignancies. Although reduced mid-upper arm circumference and weight-for-age were associated with HIV seropositivity, these clinical parameters had low positive predictive values compared to the CDC classification.     

Expression of the c-erbB-3 gene product in gastric cancer

The pattern of c-erbB-3 gene product was studied in 91 advanced gastric carcinomas, adjacent hyperplastic mucosa, intestinal metaplasia and dysplasia and in normal controls, using immunohistochemistry in archival material. All tumours showed positive c-erbB-3 staining in both cytoplasm and membrane. No significant differences of expression were observed between intestinal and diffuse-type carcinomas or any other clinical parameters. Of interest is the expression in the adjacent mucosa, which is extensive, cytoplasmic, and of lower intensity than in the tumours. Further studies are currently being carried out to clarify the role of this protein in tumour behaviour and gastric carcinogenesis.     

On the metabolism of prostaglandins by rat brain homogenate

Using radio-immuno assays for prostaglandins and prostaglandin metabolites, three prostaglandin metabolizing enzymes were found in the 100,000 X g supernatant of rat brain, 15-hydroxy-prostaglandin-dehydrogenase, delta13-reductase and prostaglandin E-9-keto-reductase. Specific activity of the latter enzyme was highest in striatum and midbrain and lowest in cortex, cerebellum and spinal cord.     

Design, synthesis, and conformational analysis of a novel series of HIV protease inhibitors

A combination of structure-based design and both solution, and solid-phase synthesis were utilized to derive a potent (nM) series of HIV-1 protease inhibitors bearing a structurally novel backbone. Detailed structural analysis of several inhibitors prepared in this series has suggested that rigidification of the P1/P2 region of this class of molecules may result in compounds with improved potency.     

Effects of amperozide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol

Ventilatory acclimatization to sustained hypoxia (VASH) is the time-dependent increase in ventilation that occurs during prolonged exposure to hypoxia. We tested the hypothesis that carotid body (CB) dopaminergic mechanisms are down-regulated during VASH, which would allow CB afferent discharge and ventilation to increase beyond the initial response to hypoxia. Domperidone (DOM; 1.0 mg.kg-1) was administered intravenously to block CB dopamine (DA) receptors after VASH was complete in awake goats. DOM caused a significant augmentation of the ventilatory response to hypoxia in acclimatized goats, failing to support the hypothesis. We conclude that inhibitory CB dopaminergic function is not significantly reduced following prolonged hypoxia, and that down-regulation of CB dopaminergic mechanisms may not be involved in VASH in the goat.