Efficacy of inotropic support of the failing heart

The clinical literature on the subject of inotropic therapy of heart failure, particularly use of digitalis glycosides, is full of contradictions. Most of this disparity can be accounted for if not reconciled by taking the methodology of the clinical trials into consideration. Because drug interventions may produce subtle effects requiring a subjective determination, the questions being asked in these studies cannot be answered without removing as many sources of bias as possible from the patient management and data analysis. If a study has not been adequately randomized, double-blinded, and placebo-controlled, the clinical findings will be inconclusive at best. Systolic myocardial dysfunction plays a pivotal role in the pathogenesis of CHF in many patients and is a prerequisite for the use of cardiotonic drugs. Although the clinical signs of heart failure may be relieved initially by diuretics and vasodilators, compensation may require the addition of a positive inotrope, particularly in advanced cases. In veterinary medicine, the choice of positive inotrope is limited to digoxin, digitoxin, dobutamine, or amrinone. Digoxin possesses superior pharmacokinetics and is the cardiac glycoside of choice for use in the dog. Dobutamine and amrinone are more potent inotropes, but since they must be administered by continuous intravenous infusion, their use is limited to critical care therapy. At the present time, only digoxin can be administered orally for sustained long-term maintenance therapy. Milrinone, a more potent derivative of amrinone, also offers this option, but it has not been available since its brief trial debut as an investigational drug. None of the nonglycoside alternatives couples the benefits of positive inotropic and negative chronotropic effects. Consequently, digoxin remains the mainstay for chronic inotropic support of the heart. Atrial fibrillation with a rapid ventricular response rate is the prime indication for digoxin. In the last few years, evidence from methodologically sound clinical trials on humans has also restored faith in the efficacy of digoxin for treating heart failure in patients with normal sinus rhythm. From these studies, the profile of a digitalis responsive heart failure patient has emerged. Digoxin is most likely to be efficacious when heart failure is associated with chronic, severe ventricular systolic dysfunction, which has resulted in ventricular dilatation. The most reliable clinical marker is the presence of a third heart sound (gallop rhythm). Although the patients in the worst heart failure generally have the shortest survival time, they may also have the most dramatic short-term clinical benefit. However, once cardiac reserve is exhausted in the terminal stages of failure, cardiotonic stimulation ceases to be effective.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of dietary selenium on humoral immunocompetence of ponies

Fifteen Shetland ponies were used in a 7-wk trial to study the effect of supplemental Se on humoral antibody production. Four 3-yr-old, five 2-yr-old and six yearling ponies were depleted of Se before being assigned randomly to either a low Se (.02 ppm) or higher Se (.22 ppm) diet. Each pony was challenged antigenically with 2 ml of sheep packed red blood cells upon receiving its respective diet and again 2 wk post-treatment. Blood samples were drawn weekly and assayed for glutathione peroxidase activity, Se and immunoglobulin concentration and antibody titers. Compared with those ponies receiving the low Se concentrate, ponies receiving the Se-supplemented diet had higher (P less than .01) glutathione peroxidase activities and blood Se concentrations during the later weeks of the experiment. An enhanced primary response was observed in Se-supplemented ponies as evidenced by increased hemagglutination titers. Higher IgG concentrations (P less than .01) also were observed in the Se-supplemented group. Dietary Se concentration of .02 ppm was inadequate for optimum immune function in the equine.     

Elevated manganese levels in blood and central nervous system occur before onset of clinical signs in scrapie and bovine spongiform encephalopathy

Prion diseases, or transmissible spongiform encephalopathies, are neurodegenerative diseases that can only be accurately diagnosed by analysis of central nervous system tissue for the presence of an abnormal isoform of the prion protein known as PrP(Sc). Furthermore, these diseases have long incubation periods during which there are no clear symptoms but where the infectious agent could still be present in the tissues. Therefore, the development of diagnostic assays to detect a surrogate marker for the presence of prion disease is essential. Previous studies on mice experimentally infected with scrapie, an ovine spongiform encephalopathy, suggested that changes in the levels of Mn occur in the blood and brain before the onset of symptoms of the disease. To assess whether these findings have relevance to the animal diseases scrapie and bovine spongiform encephalopathy, tissues from bovine spongiform encephalopathy- and scrapie-infected cattle and sheep were analyzed for their metal content and compared with values for noninfected animals. In field cases and experimentally infected animals, elevated Mn was associated with prion infection. Although some central nervous system regions showed elevated Mn, other regions did not. The most consistent finding was an elevation of Mn in blood. This change was present in experimentally infected animals before the onset of symptoms. In scrapie-infected sheep, elevated Mn levels occurred regardless of the genotype of the sheep and were even detected in scrapie-resistant sheep in which no symptoms of disease were detected. These findings suggest that elevated blood Mn could be a potential diagnostic marker for prion infection even in the absence of apparent clinical disease.     

Gram-negative identification card for identification of Salmonella, Escherichia coli, and other Enterobacteriaceae isolated from foods: collaborative study

Twelve laboratories evaluated the Gram-Negative Identification (GNI) Card to identify members of the Enterobacteriaceae. Eighty-four isolates, previously isolated from foods, were used in the collaborative study; the isolates represented 12 genera within the Enterobacteriaceae group. Each collaborator streaked each isolate on tryptic soy agar plates for purity. In the method, plates are incubated 18-24 h at 35 degrees C. Isolated colonies are then subcultured to tryptic soy agar slants and incubated 18-24 h at 35 degrees C. An emulsion is made from the growth on the slant in 1.8 mL 0.45% sodium chloride solution. The GNI Card is filled and placed in a reader/incubator. Isolates are identified and an identification is printed. The Vitek System correctly identified 96.7% of Salmonella sp., 97.0% of Escherichia coli, and an average of 93.8% of the other enteric genera. The method using the Vitek System and GNI Card has been approved interim official first action by AOAC as a screening method for the presumptive identification of Salmonella sp., E. coli, and other Enterobacteriaceae isolated from foods.     

Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans

Coevolution of mammals and their gut microbiota has profoundly affected their radiation into myriad habitats. We used shotgun sequencing of microbial community DNA and targeted sequencing of bacterial 16S ribosomal RNA genes to gain an understanding of how microbial communities adapt to extremes of diet. We sampled fecal DNA from 33 mammalian species and 18 humans who kept detailed diet records, and we found that the adaptation of the microbiota to diet is similar across different mammalian lineages. Functional repertoires of microbiome genes, such as those encoding carbohydrate-active enzymes and proteases, can be predicted from bacterial species assemblages. These results illustrate the value of characterizing vertebrate gut microbiomes to understand host evolutionary histories at a supraorganismal level.     

Very-Long-Baseline Radio Interferometry: The Mark III System for Geodesy, Astrometry, and Aperture Synthesis

The Mark III very-long-baseline interferometry (VLBI) system allows recording and later processing of up to 112 megabits per second from each radio telescope of an interferometer array. For astrometric and geodetic measurements, signals from two radio-frequency bands (2.2 to 2.3 and 8.2 to 8.6 gigahertz) are sampled and recorded simultaneously at all antenna sites. From these dual-band recordings the relative group delays of signals arriving at each pair of sites can be corrected for the contributions due to the ionosphere. For many radio sources for which the signals are sufficiently intense, these group delays can be determined with uncertainties under 50 picoseconds. Relative positions of widely separated antennas and celestial coordinates of radio sources have been determined from such measurements with 1 standard deviation uncertainties of about 5 centimeters and 3 milliseconds of arc, respectively. Sample results are given for the lengths of baselines between three antennas in the United States and three in Europe as well as for the arc lengths between the positions of six extragalactic radio sources. There is no significant evidence of change in any of these quantities. For mapping the brightness distribution of such compact radio sources, signals of a given polarization, or of pairs of orthogonal polarizations, can be recorded in up to 28 contiguous bands each nearly 2 megahertz wide. The ability to record large bandwidths and to link together many large radio telescopes allows detection and study of compact sources with flux densities under 1 millijansky.     

镉对鲫非特异性免疫力的影响

采用毒性实验方法研究了镉对鲫非特异性免疫力的影响,确定镉诱导免疫毒性效应及其毒性参数。在试验剂量和时间范围内的结果显示,镉对鲫白细胞数量(WBC)、中性粒细胞的吞噬率(PR)和补体50%溶血活性(CH50)均有剂量-效应关系、时间-效应关系和Hormesis现象,1.25mg·kg-1注射染Cd2+胁迫时对WBC、PR和CH50有激活作用,2.5和3.75mg·kg-1注射染Cd2+胁迫时对WBC、PR和CH50有抑制作用;WBC顶点所对应的时间为染Cd2+后4d,PR顶点所对应的时间为染Cd2+后2d,CH50顶点所对应的时间为染Cd2+后1d。所以Cd2+对鲫具有明显的免疫毒性。     

Negative linear compressibility and massive anisotropic thermal expansion in methanol monohydrate

The vast majority of materials shrink in all directions when hydrostatically compressed; exceptions include certain metallic or polymer foam structures, which may exhibit negative linear compressibility (NLC) (that is, they expand in one or more directions under hydrostatic compression). Materials that exhibit this property at the molecular level--crystalline solids with intrinsic NLC--are extremely uncommon. With the use of neutron powder diffraction, we have discovered and characterized both NLC and extremely anisotropic thermal expansion, including negative thermal expansion (NTE) along the NLC axis, in a simple molecular crystal (the deuterated 1:1 compound of methanol and water). Apically linked rhombuses, which are formed by the bridging of hydroxyl-water chains with methyl groups, extend along the axis of NLC/NTE and lead to the observed behavior.