Effects of serotonin and the serotonin blocker metergoline on meal patterns and macronutrient selection

Serotonin [5-hydroxytryptamine(5-HT)] in the paraventricular nucleus (PVN) of rats has a suppressive effect on feeding behavior and causes a selective decrease in carbohydrate ingestion, specifically at the onset of the natural (dark) feeding period. Studies conducted here provide further evidence for this phenomena, showing a similar dose-related decrease in carbohydrate ingestion at dark onset after PVN injection of 5-HT or of the agonists, d-norfenfluramine or fluoxetine, which act through endogenous 5-HT. To further characterize the effects of this indoleamine on the macrostructure of feeding, a computer-automated data acquisition system was used to analyze macronutrient feeding patterns in freely feeding animals maintained on the pure diets of protein, carbohydrate, and fat. Results indicate that PVN administration of 5-HT at dark onset decreases intake of the carbohydrate nutrient by decreasing meal size, feeding time, and feeding rate for this nutrient and increasing the satiating effect of carbohydrate. These effects, which occur specifically during the first meal after injection, are opposite those seen after peripheral administration of the 5-HT receptor antagonist, metergoline. This drug stimulates feeding through a selective increase in carbohydrate intake, characterized by an increase in meal size, percent composition, and feeding time for this nutrient and a decrease in the satiety ratio for carbohydrate. These results implicate the serotonergic system in the termination of carbohydrate-rich meals that are prevalent during the early hours of the natural feeding cycle.     

ATP-Dependent inhibition of Ca2+-activated K+ channels in vascular smooth muscle cells by neuropeptide Y

Neuropeptide Y(NPY) inhibits Ca2+-activated K+ channels reversibly in vascular smooth muscle cells from the rat tail artery. NPY (200 microM) had no effect in the absence of intracellular adenosine 5'-triphosphate (ATP) and when the metabolic poison cyanide-M-chlorophenyl hydrozone (10 microM) was included in the intracellular pipette solution. NPY was also not effective when ATP was substituted by the non-hydrolysable ATP analogue adenosine 5'-[beta gamma-methylene]-triphosphate (AMP-PCP). NPY inhibited Ca2+-activated K+ channel activity when ATP was replaced by adenosine 5'-O-(3-thiotriphosphate) (ATP [gamma-S]) and the inhibition was not readily reversed upon washing. Protein kinase inhibitor (1 microM), a specific inhibitor of adenosine 3', 5'-cyclic monophosphate-dependent protein kinase, had no significant effect on the inhibitory action of NPY. The effect of NPY on single-channel activity was inhibited by the tyrosine kinase inhibitor genistein (10 microM) but not by daidzein, an inactive analogue of genistein. These observations suggest that the inhibition by NPY of Ca2+-activated K+ channels is mediated by ATP-dependent phosphorylation. The inhibitory effect of NPY was antagonized by the tyrosine kinase inhibitor genistein.     

Modeling electromigration lifetime under bidirectional currentstress

Electromigration reliability of interconnect under bidirectional current stress has been studied in a wide frequency range (mHz to 200 MHz). Experimental results show that the AC lifetime rises with the stress current frequency. The current density exponent and the activation energy of AC lifetime are found to be twice that of DC lifetime. Pure AC current stress failure at extremely high current density is believed to result from thermal migration of metal at hot/cold transition points     

Intercellular communication between dorsal root ganglion cells and colonic smooth muscle cells in vitro

This study demonstrates that the use of high field 1H NMR spectroscopy permits individual detection of phosphatidylcholine and sphingomyelin molecules at the surface of native low density lipoprotein (LDL) particles. Distinct behaviour was observed for the choline head group -N(CH3)3 resonances of these different phospholipids revealing preferential immobilisation for phosphatidylcholine. This suggests the existence of reversible and irreversible phosphatidylcholine-apolipoprotein B interactions and is consistent with microdomain formation at the surface monolayer of LDL. The novel resonance assignment and results show that 1H NMR can provide efficient and practical means for future studies on the structure and dynamics at the LDL surface.     

LP-BM5 virus causes changes in lactic dehydrogenase and oxygen radical production in splenocytes of C57BL/6J mice

The LP-BM5 murine leukemia virus causes acquired immunodeficiency syndrome in C57BL/6J mice (MAIDS), similar to that of AIDS in humans. The objective of this study was to determine the effect of LP-BM5 viral infection on cellular activation and membrane integrity of splenocytes. Oxidative burst in splenocytes in response to exposure to PMA (20 microg/ml) was significantly higher (p<.02) in infected than in control mice at two weeks post-infection using luminol-enhanced chemiluminescence. By 13 weeks post-infection superoxide anion production in infected mice was significantly lower when compared to controls coinciding with decreased proliferative response to mitogens. The extent of cell membrane damage as indicated by lactic dehydrogenase (LDH) activity in serum was significantly higher in infected than in control mice (p<.001). The results from this study suggests that LP-BM5 virus causes an initial stimulation of cellular activity followed by a decreased cell activation characterized by decreased proliferation of splenocytes and decreased oxygen radical production. Decreased cell membrane integrity indicated by increased LDH activity may partly be responsible for these changes.     

Antiserum against Escherichia coli J5 contains antibodies reactive with outer membrane proteins of heterologous gram-negative bacteria

The binding of IgG in antiserum to Escherichia coli J5 to the surface of Enterobacteriaceae and to cell wall fragments released from serum-exposed bacteria was studied in a search for potentially protective epitopes other than lipopolysaccharide (LPS). IgG titers to multiple heterologous gram-negative smooth bacteria increased following incubation of the bacteria in serum and decreased following absorption with serum-exposed heterologous bacteria. IgG eluted from absorbing bacteria bound to at least three conserved bacterial outer membrane proteins (OMPs), but not LPS, as assessed by immunoblotting. The same OMPs were present in LPS-containing macromolecular cell wall fragments released by incubation of heterologous gram-negative bacteria in human serum. Part of the protection offered by J5 antiserum could be from binding of IgG to conserved OMPs at the bacterial surface or to OMPs in cell-wall fragments released from dying bacteria.     

Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene

The authors have designed and constructed a plant-optimize synthetic gene encoding the Escherichia coli heat-labile enterotoxin B subunit (LT-B), for use in transgenic plants as an edible vaccine against enterotoxigenic E. coli. Expression of the synthetic LT-B gene in potato plants under the control of a constitutive promoter yielded increased accumulation of LT-B in leaves and tubers, as compared to the bacterial LT-B gene. The plant-derived LT-B assembled into native pentameric structures as evidenced by its ability to bind ganglioside. The authors demonstrated immunogenicity by feeding mice the raw tubers and comparing the anti-LT-B serum IgG and faecal IgA to that produced in mice gavaged with bacterial LT-B. Mice were fed three weekly doses of 5 g tuber tissue containing either 20 or 50 micrograms LT-B, or gavaged weekly with 5 micrograms of LT-B from recombinant E. coli. One week after the third dose, mice immunized with potato LT-B had higher levels of serum and mucosal anti-LT-B than those gavaged with bacterial LT-B. Mice were challenged by oral administration of 25 micrograms LT, and protection assessed by comparing the gut/carcass mass ratios. Although none of the mice were completely protected, the higher dose potato vaccine compared favourably with the bacterial vaccine. These findings show that an edible vaccine against E. coli LT-B is feasible.     

Static and free vibration analysis of variable-depth bridges of arbitrary alignments using the isoparametric spline finite strip method

The isoparametric spline finite strips for shells are employed to solve static and free vibration problems of variable-depth bridges of arbitrary alignments. Using this approach, a continuous bridge is first split up into substructures. Each substructure is modelled as an assemblage of isoparametric spline finite strips. Compatibility between substructures is ensured by suitable transformation at the interface. The presence of support diaphragms and bearings can also be accounted for. This method retains the computational efficiency of the spline finite strip method while it is much more flexible in geometric modelling. Solutions of this method are compared with other available solutions, and good agreement is observed.