REPERFUSION FOLLOWING MYOCARDIAL ISCHAEMIA ENHANCES INOSITOL PHOSPHATE RELEASE IN THE ISOLATED PERFUSED RAT HEART

1. Global myocariial ischaemia (MI) for periods greater tan 5 min caused an inhibition of phosphatidylinositol specific phospholipase C (PtdIns-PLC) activity. 2. Two min reperfusion following a 20 min MI period, a time point associated with reperfusion-induced arrhythmias, resulted in an activation of PtdIns-PLC activity, dependent on endogenous noradrenaline and mediated via al-adrenoceptors. 3. This 2 min reperfusion response, in contrast to healthy myocardium, resulted in: (i) enhanced PtdIns-PLC activity; (ii) increased sensitivity to endogenous noradrenaline; (iii) rapid increases in inositol(1,4,5)trisphosphate (Ins(1,4,5)P3); and (iv) PLC hydrolysis primarily of PtdIns(4,5)P₂, such that the majority of InsP isomers derive from Ins(1,4,5)P₃. 4. Together, these data suggest a functional role for Ins(1,4,5)P3 under postischaemic reperfusion conditions, and provide a possible link between al-adrenoceptor stimulation of the PtdIns turnover pathway and reperfusion injury.     

Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers

Ten healthy subjects received buspirone (30 mg orally) with and without pre-treatment with the 5-HT1A receptor antagonist, pindolol (80 mg over 3 days). Following pindolol treatment the growth hormone and hypothermic responses to buspirone were significantly decreased. There was also a delay in the onset of the prolactin response to buspirone but the total amount of prolactin secretion, calculated as area under the curve, was not significantly reduced. The data suggest that the growth hormone and hypothermic responses to buspirone in humans are mediated by 5-HT1A receptors, but an explanation founded on pharmacokinetic factors cannot presently be excluded. Both this latter possibility and the lack of selectivity of pindolol for 5-HT receptors indicate the need for the further neuroendocrine studies of the mode of action of buspirone, preferably with more selective 5-HT1A receptor antagonists.     

Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B signal transduction pathway.

Studies presented here show that overall NF-kappa B signal transduction begins with a parallel series of stimuli-specific pathways through which cytokines (tumor necrosis factor alpha), oxidants (hydrogen peroxide and mitomycin C), and phorbol ester (phorbol 12-myristate 13-acetate) individually initiate signaling. These initial pathways culminate in a common pathway through which all of the stimulating agents ultimately signal NF-kappa B activation. We distinguish the stimuli-specific pathways by showing that the oxidative stimuli trigger NF-kappa B activation in only one of two human T-cell lines (Wurzburg but not Jurkat), whereas tumor necrosis factor alpha and phorbol 12-myristate 13-acetate readily stimulate in both lines. We propose the common pathway as the simplest way of accounting for the common requirements and properties of the signaling pathway. We include a redox-regulatory mechanism(s) in this common pathway to account for the previously demonstrated redox regulation of NF-kappa B activation in Jurkat cells (in which oxidants don't activate NF-kappa B); we put tyrosine phosphorylation in the common pathway by showing that kinase activity (inhibitable by herbimycin A and tyrphostin 47) is required for NF-kappa B activation by all stimuli tested in both cell lines. Since internal sites of oxidant production have been shown to play a key role in the cytokine-stimulated activation of NF-kappa B, and since tyrosine kinase and phosphatase activities are known to be altered by oxidants, these findings suggest that intracellular redox status controls NF-kappa B activation by regulating tyrosine phosphorylation event(s) within the common step of the NF-kappa B signal transduction pathway.     

Effect of Glycemic Carbohydrates on Short-term Satiety and Food Intake

We examine the relationships between glycemic carbohydrate and its effects on short-term satiety and food intake. Both high- and low-glycemic carbohydrates have an impact on satiety, but their effects have different time courses. High-glycemic carbohydrates are associated with a reduction in appetite and food intake in the short term (e.g., one hour), whereas the satiating effects of lower-glycemic carbohydrates appear to be delayed (e.g., 2 to 3 hours). There is no consistent evidence that an increase in blood glucose, either acute or sustained, is the primary determinant of their effects on food intake and satiety. Many other preabsorptive and postabsorptive signals for satiety exist and may be the determining factors. Further studies are needed to delineate the role of glycemic carbohydrates and their mechanisms of action in determining satiety.     

AN UNUSUAL CAUSE OF RECTOVAGINAL FISTULA

An unusual case of rectovaginal fistula is reported. An 81 year old woman presented to the geriatric team with a request to review her faecal incontinence. It was discovered that she had a predilection for placing foreign objects in her vagina. In this instance a carbonated drink top had formed a rectovaginal fistula.     

Effects of methyl isocyanate on rat muscle cells in culture.

Since the Bhopal disaster, in which the causal agent was methyl isocyanate (MIC), exposed people have complained of various disorders including neuromuscular dysfunction. In an attempt to gain some information about the response of muscle tissue to MIC its effects were investigated in cells in culture isolated from muscle of 2 day old rats. After treatment with a range of MIC concentrations (0.025-0.5 microliter/5 ml culture) the total number of nuclei of the two main cell types (fibroblasts and myoblasts) and the number of nuclei in muscle fibres (myotubes) were recorded. At lower doses which had little effect on the total number of nuclei, the formation of muscle fibres--that is, fusion of muscle cells--was prevented as the proportion of nuclei in myotubes was decreased. At higher doses both cell types were killed. This would suggest either an effect on muscle differentiation or a selective toxicity towards myoblasts. The observations were supported by light and electron microscopy.     

Inpatient management of asthma in the Chicago suburbs: the Suburban Asthma Management Initiative (SAMI).

BACKGROUND: Assessment of inpatient asthma management has generally been limited to urban settings, including Chicago, which is known for its high asthma morbidity and mortality. Previously published data have been based on survey methodology. The Suburban Asthma Consortium (SAC) sought to obtain patient-based data unique to the Chicago suburbs to improve asthma care in those areas. OBJECTIVE: To evaluate current inpatient asthma management based on the 1997 National Asthma Education and Prevention Program (NAEPP). DESIGN: Retrospective chart review of all hospitalized patients 3-65 years bearing asthma-related ICD-9 codes for fiscal year 2002 in community, nonteaching hospitals in Chicago suburbs. RESULTS: Nine hundred two cases were submitted from seven hospitals. The majority ( > or = 75%) received inhaled bronchodilators, systemic steroids, oxygen and pulse oximetry. Antibiotic use (67%), chest radiography (85%), complete blood count (77%), and electrolytes (59%) appeared excessive in view of NAEPP recommendations. Peak flow monitoring (PFM) was recorded on admission in 45% of patients 5 years old and older; 52% had PFM during hospitalization. Thirty-eight percent of patients were taking ICS prior to admission; of those not on ICS, only 12% were newly diagnosed asthmatics. Overall, 51% of patients were discharged with ICS. Patients were more likely to receive ICS at discharge if they had required intensive care (ICU), had been on ICS prior to admission, were referred to an asthma specialist while hospitalized, or were insured. Patients with Medicare/Medicaid (MC/MA) had more repeat emergency visits and hospitalizations, longer lengths of stay, and received less ICS at discharge. Depending on the parameter, 41% or less patients received discharge planning education and were not more likely to have received education if in the ICU. Results ranged significantly between hospitals for most parameters (p < 0.05 or less). CONCLUSION: Study subjects received appropriate acute therapy and oxygen monitoring, but there was a divergence from NAEPP recommendations regarding PFM, ICS use, antibiotics, and laboratory evaluation. Patients receiving MC/MA experienced higher morbidity and received less ICS. Discharge asthma education was suboptimal for most hospitals. Most parameters demonstrated significantly wide practice variations between hospitals. Peak flow monitoring and patient education findings differed significantly from those in survey-conducted studies.