Pilocarpine-induced seizure-like activity with increased BNDF and neuropeptide Y expression in organotypic hippocampal slice cultures

Organotypic hippocampal slice cultures were treated with the muscarinic agonist pilocarpine to study induced seizure-like activity and changes in neurotrophin and neuropeptide expression. For establishment of a seizure-inducing protocol, 2-week-old cultures derived from 6–8-day-old rats were exposed to 0.1 mM to 5 mM of pilocarpine for 4 h to 7 days. Other cultures were treated with pilocarpine for 7 days and left for 7–14 days in normal medium. Age-matched, non-treated cultures served as controls. Intracellular recordings from CA1 pyramidal cells revealed increased spontaneous activity in 31 of 35 cultures superfused with 0.1 or 5 mM pilocarpine. Epileptiform discharges were recorded in 17 of the 31 cultures, and 19 displayed frequencies specifically in the 6–12-Hz (Theta rhythm) range when superfused with pilocarpine. The pilocarpine effect was blocked by simultaneous superfusion with the muscarinic receptor antagonist atropine (100 μM). Regardless of dose and exposure time, the pilocarpine treatment induced very limited neuronal cell death, recorded as cellular propidium iodide uptake. Cultures exposed to 5 mM pilocarpine for up to 7 days displayed increased BDNF expression when analyzed by Western blot and ELISA. This BDNF increase correlated with increased neuropeptide Y immunoreactivity, known to accompany seizure activity. Addition of BDNF (200 ng/ml) to otherwise untreated cultures also upregulated NPY expression. The pilocarpine-induced seizure-like activity in hippocampal slice cultures, with concomitant increase in BDNF and NPY expression, is compared with in vivo observations and discussed in terms of the potential use of the easily accessible slice cultures in experimental seizure research.     

In vitro blood-brain barrier permeability and cerebral endothelial cell uptake of the neuroprotective nitrone compound NXY-059 in normoxic,hypoxic and ischemic conditions

The free radical trapping nitrone compounds alpha-phenyl-N-tert-butylnitrone (PBN), 2-sulfophenyl-N-tert-butylnitrone (S-PBN) and disodium 2,4-disulfophenyl-N-tert-butyl nitrone (NXY-059) are effective neuroprotective agents in experimental models of both transient and permanent focal ischemia. A recent in vivo study suggested that NXY-059 had poor brain uptake in a transient ischemia model. We have now examined its blood-brain barrier permeability and cerebral endothelial uptake during hypoxic and ischemic conditions using an in vitro model of the blood-brain barrier. The in vitro blood-brain barrier permeability and cerebral endothelial uptake of NXY-059 and S-PBN were low during normoxic conditions. In contrast, PBN had very high blood-brain barrier penetration in vitro which confirmed earlier in vivo results. The permeability of [14C]NXY-059 increased 3.5 times after 9 h of hypoxia or 3 h of ischemia. There was, respectively, a 5-fold and more than 10-fold increase, after 6 and 9 h of ischemia. The control molecule [3H]inulin (M(r) approximately 5000) showed a similar increase in permeability under the same experimental conditions indicating a major change in the transport properties of the endothelium. There was a 60% reduction in the ATP levels of astrocytes after 3 h of ischemia and a 90% reduction after 9 h. The reduction in ATP levels in endothelial cells was somewhat lower. The uptake of NXY-059 in cerebral endothelial cells under normoxic, hypoxic or 9 h of ischemic conditions was negligible. NXY-059, S-PBN and PBN showed no effects on vesicular transport or the integrity of the blood-brain barrier in normoxic or ischemic conditions, nor did the compounds induce any change in the ATP levels of the cells. In conclusion, it is possible that the increase in blood-brain barrier permeability of [14C]NXY-059 which occurs during prolonged ischemia in vitro reflects a change which may be of importance to the neuroprotective effects of this nitrone free radical trapping agent.     

Acute eosinophilic pneumonia in a New York City firefighter exposed to World Trade Center dust

We report a sentinel case of acute eosinophilic pneumonia in a firefighter exposed to high concentrations of World Trade Center dust during the rescue effort from September 11 to 24. The firefighter presented with a Pa(O2) of 53 mm Hg and responded to oxygen and corticosteroids. Computed tomography scan showed patchy ground glass density, thickened bronchial walls, and bilateral pleural effusions. Bronchoalveolar lavage recovered 70% eosinophils, with only 1% eosinophils in peripheral blood. Eosinophils were not degranulated and increased levels of interleukin-5 were measured in bronchoalveolar lavage and serum. Mineralogic analysis counted 305 commercial asbestos fibers/10(6) macrophages including those with high aspect ratios, and significant quantities of fly ash and degraded fibrous glass. Acute eosinophilic pneumonia is a rare consequence of acute high dust exposure. World Trade Center dust consists of large particle-size silicates, but fly ash and asbestos fibers may be found in bronchoalveolar lavage cells.     

The p53 codon 72 polymorphism in black South African women and the risk of cervical cancer

The p53 codon 72 genotype was examined in blood samples taken from 121 Zulu-speaking black South African women with histologically proven squamous carcinoma of the cervix. Freshly biopsied tumour tissue was also available for human papillomavirus subtyping from 100 of these women. A control group consisted of 251 healthy race-matched women attending a contraceptive service facility. The results show that there were no statistically significant differences in the frequency of the homozygous arginine genotype between patients with cancer of cervix, irrespective of human papillomavirus status, and healthy controls. This finding suggests that the arginine allele does not predispose towards viral tumour genesis in this population, and supports the findings of research done in other ethnic groups.     

Delivery of Soluble Tumor Necrosis Factor Receptor from In-Situ Forming PLGA Implants: In-Vivo

Pharmaceutical Research -     

Analysis of the role of thyroidectomy and thymectomy in the surgical treatment of secondary hyperparathyroidism

Purpose

Parathyroidectomy can be subtotal or total with an autograft for the treatment of renal hyperparathyroidism. In both cases, it may be extended with bilateral thymectomy and total or partial thyroidectomy. Thymectomy may be recommended in combination with parathyroidectomy in order to prevent mediastinal recurrence. Also, the occurrence of thyroid disease observed in patients with hyperparathyroidism is poorly understood and the incidence of cancer is controversial. The aim of the present study was to report the experience of a single center in the surgical treatment of renal hyperparathyroidism and to analyse the role of thyroid and thymus surgery in association with parathyroidectomy.

Seroprevalence of hepatitis C virus and associated risk behaviours: a population-based study in San Juan, Puerto Rico

BACKGROUND: Limited information about the epidemiology of hepatitis C virus (HCV) infection is available in Puerto Rico, one of the areas hardest hit by the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) epidemic. We estimated the prevalence of HCV infection and identified correlates of seropositivity in the municipality of San Juan, Puerto Rico. METHODS: A probability cluster design was employed to select a sample of households representative of the population aged 21-64 years in San Juan during 2001-2002. All 964 subjects completed a face-to-face interview to gather data on demographics and self-reported risk behaviours followed by venipuncture for HCV antibody testing. Variables that were at least marginally associated with HCV seroprevalence (P < 0.10) in the bivariate analyses were considered for inclusion into the multiple logistic regression model to estimate the adjusted prevalence odds ratio (POR). RESULTS: Overall weighted prevalence of HCV infection was 6.3% (95% CI 3.6-10.9%). A significant (P < 0.05) higher prevalence was observed among subjects with the following characteristics: age 30-49 (9.5%), male sex (10.6%), < or =12 years of education (9.6%), no health coverage (12.6%), lifetime heroin use (39.2%), lifetime cocaine use (39.6%), tattooing practices (34.2%), history of imprisonment (32.8%), and self-reported histories of hepatitis B virus infection (30.4%) and HIV/AIDS (92.1%). Multivariate logistic regression revealed that tattooing practices (POR = 8.9; 95% CI 1.7-44.7), lifetime cocaine use (POR = 5.5; 95% CI 2.2-13.5), blood transfusions prior to 1992 (POR = 4.0; 95% CI 1.6-10.1), lifetime heroin use (POR = 3.3; 95% CI 1.4-7.8), and history of imprisonment (POR = 2.3; 95% CI 1.1-4.9) remained significantly associated with HCV seropositivity. CONCLUSIONS: The large prevalence of HCV infection observed in Puerto Rican adults residing in San Juan suggest that HCV infection is an emerging public health concern and merits further investigation.