A novel effect of bismuth ions: selective inhibition of the biological activity of glycine-extended gastrin

Although bismuth salts have been used for over two centuries for the treatment of various gastrointestinal disorders, the mechanism of their therapeutic action remains controversial. Because gastrins bind two trivalent ferric ions with high affinity, and because ferric ions are essential for the biological activity of glycine-extended gastrin 17, we have investigated the hypothesis that trivalent bismuth ions influence the biological activity of gastrins. Binding of bismuth ions to gastrins was measured by fluorescence quenching and NMR spectroscopy. The effects of bismuth ions on gastrin-stimulated biological activities were measured in inositol phosphate, cell proliferation, and cell migration assays. Fluorescence quenching experiments indicated that both glycine-extended and amidated gastrin 17 bound two bismuth ions. The NMR spectral changes observed on addition of bismuth ions revealed that Glu-7 acted as a ligand at the first bismuth ion binding site. In the presence of bismuth ions the ability of glycine-extended gastrin 17 to stimulate inositol phosphate production, cell proliferation, and cell migration was markedly reduced. In contrast, bismuth ions had little effect on the affinity of the CCK-2 receptor for amidated gastrin 17, or on the stimulation of inositol phosphate production by amidated gastrin 17. We conclude that bismuth ions may act, at least in part, by blocking the effects of glycine-extended gastrin 17 on cell proliferation and cell migration in the gastrointestinal tract. This is the first report of a specific inhibitory effect of bismuth ions on the action of a gastrointestinal hormone.     

A Quantitative Analysis of Secretion-Grooming Behaviour in the Water Bug Plea minutissima Leach (Heteroptera,Pleidae): Control by Abiotic Factors

The pigmy backswimmer, Plea minutissima, from time to time leaves the water to apply its antimicrobial metathoracic gland secretion to its water-repellent ventral pubescence (“secretion-grooming”) which is enclosed by an air sheath when submerged and has a respiratory function. Secretion-grooming keeps the hairs free of microbial contamination and thus hydrophobous and functional. The grooming behaviour is regulated by abiotic factors. It is released by an increase in light intensity or water temperature, with a sudden rise in temperature being particularly effective. The higher the temperature and light intensity, the faster the grooming act is performed and completed. The grooming motivation is higher at a higher ambient temperature, but declines once the behaviour has been brought to completion. As a consequence the highest grooming activity in the field is observed in summer on the first sunny day after a prolonged period of overcast days. The tying of secretion-grooming to abiotic factors probably serves to destroy epizoic microorganisms before they begin to multiply more rapidly at higher temperatures. The mechanisms regulating the secretion-grooming behaviour of Plea may be of significance also for the regulation of certain other insect behaviours (e.g., flight behaviour).     

Respiratory chain defect of myocardial mitochondria in idiopathic dilated cardiomyopathy of Doberman pinscher dogs.

Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of unknown cause. We tested the hypothesis that IDCM was associated with a myocardial metabolic defect by determining a comprehensive biochemical profile of metabolite concentrations and enzyme activities for the major metabolic pathways of the myocardium. We used the Doberman pinscher breed as a naturally occurring canine model of IDCM and compared its myocardial profile with that of healthy adult mongrels. Compared with controls, myocardium in IDCM had markedly reduced mitochondrial electron transport activity and myoglobin concentration, in association with acidosis and energy depletion following anoxic challenge: 60% decreased NADH dehydrogenase and 50% decreased ATP synthetase activities; 90% decreased myoglobin concentration; and 30% reduced ATP and 50% increased lactate and proton concentrations. Sarcoplasmic reticulum Ca(2+)-transport ATPase was decreased by 42%. There was a 15% compensatory increase in fatty acid oxidation and Krebs cycle activity. Other biochemical changes were mild by comparison with the mitochondrial defects. We conclude that IDCM is associated with a marked impairment of mitochondrial production of ATP, arising from decreased activity of the mitochondrial electron transport system, including myoglobin. These changes may be secondary to an underlying genetic defect or may indicate a deficiency of the mitochondrial respiratory chain that predisposes this breed to heart failure.     

Does breaking up prolonged sitting when sleep restricted affect postprandial glucose responses and subsequent sleep architecture? – a pilot study

ABSTRACT

This pilot study investigated the impact of breaking up prolonged sitting with light-intensity walking on postprandial glucose responses and sleep architecture. In a randomized, counterbalanced, crossover design, six healthy males completed a sitting condition and an active condition (sitting interrupted with light-intensity walking) for three consecutive days, following 5-h sleep opportunities at night. Postprandial glucose response and sleep (time spent in all stages) was assessed. Breaking up prolonged sitting with light-intensity walking did not affect postprandial glucose responses in sleep-restricted participants; however a small increase (~9 min) in slow-wave sleep was observed.     

Plant DNA methyltransferases

DNA methylation is an important modification of DNA that plays a role in genome management and in regulating gene expression during development. Methylation is carried out by DNA methyltransferases which catalyse the transfer of a methyl group to bases within the DNA helix. Plants have at least three classes of cytosine methyltransferase which differ in protein structure and function. The METI family, homologues of the mouse Dnmt1 methyltransferase, most likely function as maintenance methyltransferases, but may also play a role in de novo methylation. The chromomethylases, which are unique to plants, may preferentially methylate DNA in heterochromatin; the remaining class, with similarity to Dnmt3 methyltransferases of mammals, are putative de novo methyltransferases. The various classes of methyltransferase may show differential activity on cytosines in different sequence contexts. Chromomethylases may preferentially methylate cytosines in CpNpG sequences while the Arabidopsis METI methyltransferase shows a preference for cytosines in CpG sequences. Additional proteins, for example DDM1, a member of the SNF2/SWI2 family of chromatin remodelling proteins, are also required for methylation of plant DNA.     

Cerebral malaria in children in South Sudan: 8 years experience in 261 cases

Two hundred-sixty-one (261) cases of cerebral malaria within last 8 years from 3 tropical clinics in South Sudan were analyzed. Coma was present at 79.8% and convulsions at 25.6%. However 90.5% of children were cured. Commonest antimalarial drugs used were intravenous quinine, clindamycin, artesunate and artemeter.     

Etiology, risks factors, therapy of nosocomial cerebrovascular infections

Nosocomial cerebrovacsular infections are substantial cause of mortality and morbidity in patients after neurosurgery. Risk factors, etiology, treatment strategies and outcome of nosocomial meningitis and brain abscess are briefly reviewed.     

Bacterial meningitis after craniocerebral trauma in the community

Craniocerebral trauma is one of major risk factors for development of meningitis. We reviewed 30 cases of bacterial meningitis occurring in community after craniocerebral trauma. Alcohol abuse was significant risk factor occurring in trauma patients with meningitis present in 50% in our cohort (p=0.0001). The most common pathogen in posttraumatic meningitis was Str. pneumoniae (90% vs. 33.8%, p=0.0001). However mortality was very low, only 5% probably because of early diagnosis and treatment of patients at risk for bacterial meningitis but neurologic sequellea were significantly more common (p=0.00001) in patients after craniocerebral trauma.