Effects of supplemental shade on thermoregulatory response of calves to heat challenge in a hutch environment

Holstein (n = 12) and Guernsey (n = 6) calves, housed in hutches, were used to evaluate the complex relationships among external environment, housing microclimate, and thermal status of calves. The study was conducted during the summer; 9 calves were housed in hutches under supplemental shade, and 9 calves were maintained in hutches under direct sunlight. Environmental and calf temperatures were measured twice daily at 0700 and 1500 h, which included determinations of air temperature, inner and outer surface temperatures of the hutch, rectal and skin temperatures of the calf, and respiration rate. Outer and inner surface temperatures of the hutch were lower under supplemental shade. Hutch air temperature was highly correlated with inner surface temperature and therefore was lower in the shaded environment. During the p.m. period, when heat stress was highest, calves housed in a shaded hutch environment had lower skin temperatures and respiration rates than did unshaded calves. Body temperature and respiration rates increased less for calves in shade than for calves in sun. These data define the relationship between the calf and the environment. Supplemental shade diminished the severity of heat stress experienced by calves that were housed in hutches during the summer.     

Cyclic nucleotides attenuate lipid peroxidation-mediated neuron toxicity

Recent studies suggest that increased lipid peroxidation and lipid peroxidation products, such as 4-hydroxynonenal (HNE), contribute to neuronal loss in conditions associated with oxidative stress. The focus of the present study was to determine possible neuroprotective effects of elevated cyclic nucleotide levels against lipid peroxidation and HNE-mediated neural toxicity. Application of 8-bromo derivative analogs of cAMP or cGMP resulted in attenuation of HNE-induced increases in mitochondrial calcium, reactive oxygen species, and neuron loss. Similar results were obtained when neural cells were pretreated with the phosphodiesterase inhibitors zaprinast or isobutylmethylxanthanine (IBMX). These data are consistent with a possible neuroprotective role for elevated cyclic nucleotide levels in disorders associated with increases in lipid peroxidation and HNE.     

A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators

BACKGROUND: Vesnarinone, an inotropic drug, was shown in a short-term placebo-controlled trial to improve survival markedly in patients with severe heart failure when given at a dose of 60 mg per day, but there was a trend toward an adverse effect on survival when the dose was 120 mg per day. In a longer-term study, we evaluated the effects of daily doses of 60 mg or 30 mg of vesnarinone, as compared with placebo, on mortality and morbidity. METHODS: We enrolled 3833 patients who had symptoms of New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 30 percent or less despite optimal treatment. The mean follow-up was 286 days. RESULTS: There were significantly fewer deaths in the placebo group (242 deaths, or 18.9 percent) than in the 60-mg vesnarinone group (292 deaths, or 22.9 percent) and longer survival (P=0.02). The increase in mortality with vesnarinone was attributed to an increase in sudden death, presumed to be due to arrhythmia. The quality of life had improved significantly more in the 60-mg vesnarinone group than in the placebo group at 8 weeks (P<0.001) and 16 weeks (P=0.003) after randomization. Trends in mortality and in measures of the quality of life in the 30-mg vesnarinone group were similar to those in the 60-mg group but not significantly different from those in the placebo group. Agranulocytosis occurred in 1.2 percent of the patients given 60 mg of vesnarinone per day and 0.2 percent of those given 30 mg of vesnarinone. CONCLUSIONS: Vesnarinone is associated with a dose-dependent increase in mortality among patients with severe heart failure, an increase that is probably related to an increase in deaths due to arrhythmia. A short-term benefit in terms of the quality of life raises issues about the appropriate therapeutic goal in treating heart failure.     

Phylogenetic and physiological diversity of sulphate-reducing bacteria isolated from a salt marsh sediment

Xenopus blastula cells activate different mesodermal genes as a concentration-dependent response to activin, which behaves like a morphogen. To understand how cells recognize morphogen concentration, we have bound naturally labeled activin to cells and related this to choice of gene activation. We find that the increasing occupancy of a single receptor type can cause cells to switch gene expression. Cells sense ligand concentration by the absolute number of occupied receptors per cell (100 and 300 molecules of bound activin induce Xbra and Xgsc, respectively, i.e., 2% and 6% of the total receptors) and not by a ratio of occupied to unoccupied receptors. The long duration of occupancy explains a previously described ratchet effect. Our results suggest a new concept of morphogen gradient formation and interpretation that is particularly well suited to the needs of early development.     

Alternate iron transport pathway. Mobilferrin and integrin in K562 cells

A transferrin-independent iron transport system in cells containing transferrin receptors was described previously by several investigators. Prior studies did not identify the proteins involved in this alternate iron transport pathway. Using a human-derived erythroleukemia tissue culture line, iron-binding proteins were isolated from cytosol and cell membranes. The cytosol protein was soluble in 60% ammonium sulfate, had a molecular mass similar to mobilferrin (56 kDa), and reacted with anti-mobilferrin antibodies. The water-insoluble radiolabeled protein was solubilized with Nonidet P-40 and immunoprecipitated with monoclonal antibody against beta 3 human integrin. Pulse-chase studies suggested sequential passage of iron to integrin, mobilferrin, and ferritin, respectively. Thus, the alternate iron transport pathway contained proteins similar to those observed in intestinal cells which did not possess transferrin receptors on their absorptive surface. The alternate iron transport pathway is only partially shared with zinc and cadmium. Mobilferrin bound zinc and iron competitively, but the two metals were not transported competitively into K562 cells. Immunoprecipitates of integrin containing radiozinc were obtained with a monoclonal antibody against beta 1 human integrin. This suggested iron and zinc may utilize different integrins to passage the cell membrane.     

1,5 Tesla MRI in focal nodular hyperplasia. Review of the literature apropos of 7 cases

There are increasing reports of unusual clinical features and atypical courses of syphilis in patients with acquired immunodeficiency syndrome. Recently, we had the opportunity to study an HIV-positive female patient with strong manifestations of secondary syphilis. The case is discussed together with the implications of secondary syphilis in her concomitant ocular affliction. Moreover, we comment on the clinico-therapeutic controversies brought about by the association of infection with Treponema pallidum and HIV.     

18F]fluoroalkyl analogues of the potent 5-HT1A antagonist WAY 100635: radiosyntheses and in vivo evaluation

Two analogues of the potent 5-HT1A antagonist WAY 100635 have been synthesized and radiolabelled with 18F, namely N-[2-[4-(2-2'-[18F] fluoroethoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xan e carboxamide ([18F]FEC) and N-[2-[4-(2-3'-[18F] fluoropropoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cycloh exa ne carboxamide ([18F]FPC). Biodistribution studies in rats showed selective uptake of both radiotracers in regions known to be rich in 5-HT1A receptors following i.v. injection. The ratio of radioactivity in hippocampus to that in the cerebellum was 5.5 (for [18F]FEC) and 7.5 (for [18F]FPC) at 60 min postinjection. Regional brain heterogeneity of radioactivity could be abolished by pretreatment with WAY 100635 and FPC but was unaffected by pretreatment with a variety of drugs including ketanserin, sulpiride, and SCH 23390. These results are compared vis-a-vis with those obtained using [11C]WAY 100635 to evaluate [18F]FEC and [18F]FPC as potential radiotracers for imaging 5-HT1A receptors by positron emission tomography.     

Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain

We have performed a multicentre trial to assess the performance of three techniques for absolute quantification of cerebral metabolites using in vivo proton nuclear magnetic resonance (NMR). The techniques included were 1) an internal water standard method, 2) an external standard method based on phantom replacement, and 3) a more sophisticated method incorporating elements of both the internal and external standard approaches, together with compartmental analysis of brain water. Only the internal water standard technique could be readily implemented at all participating sites and gave acceptable precision and interlaboratory reproducibility. This method was insensitive to many of the experimental factors affecting the performance of the alternative techniques, including effects related to loading, standing waves and B1 inhomogeneities; and practical issues of phantom positioning, user expertise and examination duration. However, the internal water standard method assumes a value for the concentration of NMR-visible water within the spectroscopic volume of interest. In general, it is necessary to modify this assumed concentration on the basis of the grey matter, white matter and cerebrospinal fluid (CSF) content of the volume, and the NMR-visible water content of the grey and white matter fractions. Combining data from 11 sites, the concentrations of the principal NMR-visible metabolites in the brains of healthy subjects (age range 20-35 years) determined using the internal water standard method were (mean+/-SD): [NAA]=10.0+/-3.4 mM (n=53), [tCho]=1.9+/-1.0 mM (n=51), [Cr + PCr]=6.5+/-3.7 mM (n=51). Evidence of system instability and other sources of error at some participating sites reinforces the need for rigorous quality assurance in quantitative spectroscopy.