A Systematic Review of Weight-Based Metoprolol for Acute Atrial Fibrillation with Rapid Ventricular Rate.

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in the emergency department (ED) and when patients present in acute AF with rapid ventricular rate (RVR), it can result in significant morbidity and mortality. Primary treatment modalities are aimed at rate control with the two most common agents being intravenous metoprolol and diltiazem. Some evidence suggests that diltiazem may be more effective at controlling rate in these patients; however, the dosing strategies, pharmacologic differences, and study designs may play a role in the observation of these differences.

Lessons in stability from thermophilic proteins.

Studies that compare proteins from thermophilic and mesophilic organisms can provide insights into ability of thermophiles to function at their high habitat temperatures and may provide clues that enable us to better define the forces that stabilize all proteins. Most of the comparative studies have focused on thermal stability and show, as expected, that thermophilic proteins have higher Tm values than their mesophilic counterparts. Although these comparisons are useful, more detailed thermodynamic analyses are required to reach a more complete understanding of the mechanisms thermophilic protein employ to remain folded over a wider range of temperatures.

Both inducible nitric oxide synthase and NADPH oxidase contribute to the control of virulent phase I Coxiella burnetii infections.

Host control of Coxiella burnetii infections is believed to be mediated primarily by activated monocytes/macrophages. The activation of macrophages by cytokines leads to the production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) that have potent antimicrobial activities. The contributions of ROI and RNI to the inhibition of C.

Vaccines against Coxiella infection.

Coxiella burnetii is an obligate intracellular bacterium that causes a worldwide zoonotic disease, Q fever. Since C. burnetii infection is an occupational hazard and could develop into severe chronic disease in humans, vaccination should be considered to protect individuals at-risk of contact with naturally infected animals or exposure to the agents.

Disruption of cadherin/catenin expression, localization, and interactions during HgCl2-induced nephrotoxicity.

The cadherin/catenin complex is an essential regulator of intercellular adhesion and is critical for the establishment of epithelial cell polarity. The purpose of this study was to (1) determine the spatial pattern of cadherin and catenin expression, colocalization, and interaction along the mouse nephron, and (2) investigate the expression, localization, and interaction of proximal tubular cadherins and catenins during mercuric chloride-induced nephrotoxicity. Using a combination of Western blot analysis, colocalization studies, and coimmunoprecipitation, we conclude that two distinct cadherin/catenin complexes exist in adult mouse kidney proximal tubules: N-cadherin/beta-catenin/alpha-catenin and E-cadherin/beta-catenin/alpha-catenin/p120-catenin.

Chronic ethanol reduces nicotine-induced dopamine release in PC12 cells.

Background: There is a high correlation between alcohol and nicotine use; that is, alcohol use is associated with high levels of smoking. One important aspect of nicotine addiction appears to be the activation of nicotinic acetylcholine receptors on dopaminergic neurons projecting from the ventral tegmental area to the nucleus accumbens. The release of dopamine from these neurons is thought to mediate, at least in part, the reward of nicotine consumption.

The use of flow cytometry to detect expression of subunits encoded by 11 Salmonella enterica serotype Typhimurium fimbrial operons.

The Salmonella enterica serotype Typhimurium (S. Typhimurium) genome contains 13 putative fimbrial operons termed agf (csg), fim, pef, lpf, bcf, saf, stb, stc, std, stf, sth, sti and stj. Evidence for in vitro expression of fimbrial proteins encoded by these operons is currently only available for agf, fim and pef.

Molecular and phenotypic analysis of the CS54 island of Salmonella enterica serotype typhimurium: identification of intestinal colonization and persistence determinants.

The shdA gene is carried on a 25-kb genetic island at centisome 54 (CS54 island) of the Salmonella enterica serotype Typhimurium chromosome. In addition to shdA, the CS54 island of Salmonella serotype Typhimurium strain LT2 contains four open reading frames designated ratA, ratB, sivI, and sivH. DNA hybridization analysis revealed that the CS54 island is comprised of two regions with distinct phylogenetic distribution within the genus Salmonella.

Cloning and porin activity of the major outer membrane protein P1 from Coxiella burnetii.

Coxiella burnetii, the etiological agent of Q fever, is a gram-negative obligate intracellular bacterium. Two striking characteristics of this microorganism are its ability to thrive within a phagolysosome and its ability to persist in the environment outside a host cell. These abilities have been attributed to the existence of C.

Osmolyte effects on helix formation in peptides and the stability of coiled-coils.

The ability of several naturally occurring substances known as osmolytes to induce helix formation in an alanine-based peptide have been investigated. As predicted by the osmophobic effect hypothesis, the osmolytes studies here do induce helix formation. Trimethylamine-N-oxide (TMAO) is the best structure-inducing osmolytes investigated here, but it is not as effective in promoting helix formation as the common cosolvent trifluoroethanol (TFE).

Papillomavirus E1 proteins: form, function, and features.

The E1 proteins are the essential origin recognition proteins for papillomavirus (PV) replication. E1 proteins bind to specific DNA elements in the viral origin of replication and assemble into hexameric helicases with the aid of a second viral protein, E2. The resultant helicase complex initiates origin DNA unwinding to provide the template for subsequent syntheses of progeny DNA.

Microtubule-dependent regulation of vasomotor tone requires Rho-kinase.

Changes in microtubule polymerization state have been shown to affect many cellular events, including the contractile properties of smooth muscle. We have previously shown that depolymerization of microtubules causes significant vasoconstriction in arterioles. This vasoconstriction does not require the endothelium or an increase in vascular smooth muscle Ca2+.

Pore-forming protein structure analysis in membranes using multiple independent fluorescence techniques.

A large number of transmembrane proteins form aqueous pores or channels in the phospholipid bilayer, but the structural bases of pore formation and assembly have been determined experimentally for only a few of the proteins and protein complexes. The polypeptide segments that form the transmembrane pore and the secondary structure that creates the aqueous-lipid interface can be identified using multiple independent fluorescence techniques (MIFT). The information obtained from several different, but complementary, fluorescence analyses, including measurements of emission intensity, fluorescence lifetime, accessibility to aqueous and to lipophilic quenching agents, and fluorescence resonance energy transfer (FRET) can be combined to characterize the nature of the protein-membrane interaction directly and unambiguously.

Effects of N-nitropyrazoles on ocular blood flow of rabbits and retinal function recovery of rat eyes after ischemic insults.

Twelve compounds of N-nitropyrazoles were studied for their effects on ocular blood flow in rabbits and retinal function recovery in rat eyes after ischemic insults. Of the twelve N-nitropyrazoles examined, nine increased choroidal blood flow while five increased retinal blood flow significantly. On the other hand, all twelve compounds increased blood flow in iris and ciliary muscle without exception.

Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling.

We have performed a screening analysis of differential gene expression using a defined in vitro model of human capillary tube formation. Gene array, differential display and cDNA library screening were used to identify both known and novel differentially expressed genes. Major findings include: the upregulation and functional importance of genes associated with basement membrane matrix assembly; the upregulation of growth factors, transcription factors, anti-apoptotic factors, markers of endothelial cell differentiation, JAK-STAT signalling molecules, adhesion receptors, proteinase inhibitors and actin regulatory proteins; and expression changes consistent with inhibition of cell cycle progression, increased cholesterol biosynthesis, decreased ubiquitin-proteasome mediated degradation, and activation of G-protein signaling pathways.

Physiology of human lymphatic contractility: a historical perspective.

The lymphatic system is a transport system that has important roles in fluid/macromolecule homeostasis, lipid absorption, metastasis and immune function. It accomplishes these roles via the generation of a regulated lymph circulation which is dependent upon valves and pumps to overcome the normal fluid pressure gradients. Lymphatic contractility plays crucial roles in the regulation and generation of lymph transport.

Dietary n-3 polyunsaturated fatty acids modulate purified murine T-cell subset activation.

Studies in humans and murine disease models have clearly shown dietary fish oil to possess anti-inflammatory properties, apparently mediated by the n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To determine the mechanisms by which dietary EPA and DHA modulate mouse T-cell activation, female C57BL/6 mice were fed diets containing either 2% safflower oil (SAF), 2% fish oil (FO), or a 2% purified EPA/DHA ethyl ester mixture for 14 days. Splenic CD4 T cells ( approximately 90% purity) or CD8 T cells ( approximately 85% purity) were incubated with agonists which act at the plasma membrane receptor level [anti(alpha)-CD3/anti(alpha)-CD28], the intracellular level (PMA/Ionomycin), or at both the receptor and intracellular levels (alphaCD3/PMA).

A putative protein inhibitor of activated STAT (PIASy) interacts with p53 and inhibits p53-mediated transactivation but not apoptosis.

The p53 protein has recently been reported to be capable of mediating apoptosis through a pathway that is not dependent on its transactivation function. We report here that the PIASy member of the protein inhibitor of activated STAT family inhibited p53's transactivation function without compromising its ability to induce apoptosis of the H1299 nonsmall cell lung carcinoma cell line. The p53 protein bound to PIASy in yeast two-hybrid assays and coprecipitated in complexes with p53 in immunoprecipitates from mammalian cells.

Adult-onset alcohol consumption induces osteopenia in female rats.

Background: Alcohol is a known risk factor for osteopenia and fracture in humans, and its effects on the skeleton have been studied extensively in animal models. Almost all studies of rats, however, have begun rats on alcohol diets while the animals were young and still growing. The purpose of the current study was to examine the effects of alcohol consumption on rats that began drinking alcohol as adults, so that the confounding effects of growth might be minimized.

NGF stimulation increases JNK2 phosphorylation and reduces caspase-3 activity in the olfactory bulb of estrogen-replaced animals.

Estrogen receptors are extensively colocalized with neurotrophins and their receptors in the rodent forebrain. We have shown previously that estrogen increases mRNA and protein expression of the nerve growth factor (NGF)-specific tyrosine kinase receptor, trkA, while decreasing expression of the universal neurotrophin receptor p75. In view of the pro-survival roles described for trks and the context-dependent stimulation of survival and cell death pathways activated by p75, differential regulation of these receptors by estrogen is likely to alter neurotrophin-dependent cell signaling.

Effects of nitric oxide donors and nitric oxide synthase substrates on ciliary muscle contracted by carbachol and endothelin for possible use in myopia prevention.

Research has suggested that the development of myopia may possibly be prevented by the use of drugs which facilitate relaxation of the intraocular ciliary muscle. We examined the effects of five nitric oxide-producing agents--two nitric oxide donors, hydralazine and sodium nitrite, and three nitric oxide synthase substrates, L-arginine, L-canavanine, and N-benzoyl-L-arginine ethyl ester--on isolated bovine ciliary muscle maximally contracted with either carbachol or endothelin-1. Of these agents, hydralazine and L-canavanine produced a relaxing effect on endothelin-1-contracted muscle that was significantly greater than relaxing effect on carbachol-contracted muscle.

Determinants of vaccine-induced resistance in animal models of pulmonary tuberculosis.

A more effective vaccine will be essential if the global tuberculosis (TB) pandemic is ever to be controlled. A large number of new tuberculosis vaccines have been developed, representing the whole range of modern strategies for vaccine formulation and delivery. There is currently no alternative to testing these new vaccines in experimental animals challenged with virulent Mycobacteriurn tuberculosis in order to assess their protective efficacy.

Biological and molecular characterization of an ECV-304-derived cell line resistant to p53-mediated apoptosis.

Upregulation of the p53 tumor suppressor protein by infection with a recombinant p53 adenovirus resulted in extensive apoptosis in ECV-304 cells and the eventual death of almost all the cells. To establish a system to elucidate the molecular mechanisms involved in p53-mediated apoptosis of these cells, we established a variant of ECV-304 that is resistant to p53-induced apoptosis by repeated infections with a recombinant p53 adenovirus. We have designated this variant as the DECV cell line (Differentiated ECV-304).

Capillary morphogenesis during human endothelial cell invasion of three-dimensional collagen matrices.

Here, we describe assay systems that utilize serum-free defined media to evaluate capillary morphogenesis during human endothelial cell (EC) invasion of three-dimensional collagen matrices. ECs invade these matrices over a 1-3-d period to form capillary tubes. Blocking antibodies to the alpha2beta1 integrin interfere with invasion and morphogenesis while other integrin blocking antibodies do not.