Vitiligo and juvenile diabetes mellitus

Five juvenile diabetics had vitiligo. In two children, the vitiligo preceded the onset of diabetes. Four of the five patients had thyroid, adrenal, or gastric antibodies or a combination of these. In three children HLA-B8 antigens were detected, and one additional patient had HLA-Bw15. Of eight nondiabetic children with vitiligo, one had abnormal glucose tolerance. To the evidence supporting an autoimmune form of diabetes mellitus we add another observation: the association of insulin-dependent diabetes and childhood vitiligo.     

Effects of feeding increasing levels of wet corn gluten feed on production and ruminal fermentation in lactating dairy cows

An experiment was conducted to evaluate the effects of increasing dietary inclusion rates of wet corn gluten feed (WCGF; Sweet Bran; Cargill Inc., Blair, NE) on milk production and rumen parameters. Four primiparous and 4 multiparous ruminally cannulated Holstein cows averaging 90 ± 13 d in milk (mean ± SD) were randomly assigned to 1 of 4 sequences in a replicated 4 × 4 Latin square experiment with 28-d periods. Treatments were diets containing 0, 11, 23, and 34% WCGF on a dry matter basis; alfalfa hay, corn silage, corn grain, soybean meal, expeller soybean meal, and mineral supplements were varied to maintain similar nutrient concentrations across diets. Performance and measures of ruminal fermentation were monitored. Linear and quadratic effects of increasing WCGF inclusion rate were assessed using mixed-model analysis. Increasing dietary WCGF linearly increased dry matter intake (26.7, 25.9, 29.3, and 29.7 kg/d for 0, 11, 23, and 34% WCGF, respectively) and milk production (36.8, 37.0, 40.1, and 38.9 kg/d). Concentrations of milk components did not differ among treatments; however, protein and lactose yields increased linearly and fat yield tended to increase linearly when more WCGF was fed. This led to greater production of energy-corrected milk (38.2, 38.8, 41.7, and 40.4 kg/d) and solids-corrected milk (35.2, 35.7, 38.5, and 37.2 kg/d), but efficiency of production linearly decreased. Increased WCGF in the diet tended to linearly decrease ruminal pH (6.18, 6.12, 6.14, and 5.91), possibly because mean particle size was below typical recommendations for all diets, and diets with greater proportions of WCGF had a smaller mean particle size. Ruminal acetate concentration decreased linearly and propionate increased linearly as WCGF inclusion rate increased. Treatments had a quadratic effect on ammonia concentration, with greater concentrations for the 0 and 34% WCGF diets. In situ digestibility of soybean hulls showed a significant diet-by-time interaction, and increasing dietary levels of WCGF linearly decreased in situ neutral detergent fiber disappearance at 24 h. Change in body condition score increased linearly with increasing WCGF inclusion rate. Results indicate that adding WCGF to dairy rations can increase energy-corrected milk yield, and this increase appears to be driven, at least in part, by an increase in dry matter intake.     

The effect of sample freezing on proton magic-angle spinning NMR spectra of biological tissue

Magic-angle spinning (MAS) has recently been shown to enhance spectral resolution in NMR examinations of intact biological tissue ex vivo. This work demonstrates that freezing certain tissue samples before examination by 1H MAS NMR can have a marked effect on their spectra. Spectra of rat kidney after freezing in liquid nitrogen, compared with spectra before freezing, showed a significant increase in signal intensities from alanine (>100%), glutamine (>40%), and glycine (>100%), and a decrease in signals assigned to lipids and other macromolecules. Some resonances--such as from leucine, valine, isoleucine, and aspartate--only became visible after freezing the tissue. These observations suggest that low temperature storage of tissue necropsies or biopsies might affect the results of a MAS NMR analysis, possibly resulting in the misinterpretation of metabolite changes to pathogen or disease effects.     

Alterations in GABAA receptor alpha 1 and alpha 4 subunit mRNA levels in thalamic relay nuclei following absence-like seizures in rats

Modification of GABAA receptor mRNA levels by seizure activity can regulate general neuronal excitability. The possibility of absence seizure-induced alteration in GABAA receptor alpha 1, alpha 4, beta 2, and gamma 2 subunit gene expression in thalamic relay nuclei was studied in a rat model of absence seizures induced by gamma-hydroxybutyric acid (GHB). We observed a marked increase in alpha 1 mRNA and a corresponding decrease in alpha 4 mRNA in thalamic relay nuclei 2-4 h after the onset of GHB-induced absence seizures (when the seizures were terminating). These changes were selective to these alpha isoforms as neither beta 2 nor gamma 2 mRNA changed following seizures and occurred only in thalamic relay nuclei but not in hippocampus, a structure from which absence seizures do not evolve. The alterations in alpha 1 and alpha 4 mRNA persisted until about 12 h, and by 24 h after the seizure-onset the mRNA levels normalized. Blocking GHB-seizures produced no change in the levels of alpha 1 and alpha 4 mRNA in thalamic relay nuclei, suggesting that seizures themselves were responsible for mRNA alterations. In order to determine if absence seizure-induced changes in alpha 1 and alpha 4 mRNA had any physiological significance, GHB was readministered in rats 6 and 24 h after the onset of seizures. The total duration of GHB-seizures was found to be significantly decreased when GHB was readministered at 6 h but not 24 h after the seizure-onset. These results suggest that absence seizures regulate GABAA receptor alpha 1 and alpha 4 gene expression in thalamic relay nuclei as a compensatory mechanism by which absence seizures are terminated.     

Emerging standardization in pharmacoeconomics

In this study, we reviewed pharmacoeconomic guidelines from the United Kingdom, Spain, Italy, Australia, Canada, and the United States to determine areas of emerging standardization. We examined the published literature, publication guidelines of major health journals, and published and unpublished recommendations from various task forces and conferences on related topics. The review revealed several general principles for which there was consensus across guidelines. These common features included the importance of using and reporting transparent methods so that readers can easily understand what calculations are being performed on which data elements, minimizing bias, and providing justification for the methods and assumptions used. Differences were detected across guidelines on the following topics: type of pharmacoeconomic assessment, perspective, comparators and data sources, data analysis, cost analysis, future cost analysis, outcomes assessment, modeling, time horizon, discounting, disclosure, and generalizability. Evolution of economic guidelines hinges on whether the primary goal is to increase the consistency or increase the validity of economic assessments. Some balance between these two objectives is desirable.     

Effects of poliovirus 3AB protein on 3D polymerase-catalyzed reaction

Poliovirus RNA replication requires the activities of a viral RNA-dependent RNA polymerase, 3Dpol, in conjunction with several additional viral and likely cellular proteins. The importance of both the 3A and 3B coding regions has been documented previously by genetic tests, and their biochemical activities have been the subject of several recent investigations. In this study, we examined the previously reported stimulation of 3D-catalyzed RNA synthesis by 3AB. We show that 3AB does not stimulate RNA synthesis on templates that are stably base paired to a primer, indicating that 3AB does not stabilize or otherwise activate 3Dpol for chain elongation. Similarly, it does not alter the kinetic parameters or binding affinities of 3D for substrates. In the absence of a primer, or in the presence of a primer that does not form a stable hybrid with the template, 3AB increases the utilization of 3'-hydroxyl termini as sites for chain elongation by 3D, and thereby stimulates RNA synthesis. 3AB may interact with and stabilize these sites and/or may recruit 3Dpol to the site, resulting in stimulation of the initiation of elongation events. We propose that this activity is required for stabilizing weak interactions that occur during nucleotidyl-protein-primed initiation events in the viral RNA replication complex.     

Prevalence of Neospora caninum and Toxoplasma gondii antibodies in sera from camels from Egypt

Sera from camels from Egypt were examined by the direct agglutination tests incorporating mercaptoethanol for antibodies to Neospora caninum and Toxoplasma gondii. Antibodies to N. caninum were found in 6 of 161 camels in titers of 1:40 (2 camels) and 1:80, 1:160, 1:640, and 1:1280 in 1 camel each, using N. caninum formalin preserved whole tachyzoites as antigen. Antibodies to T. gondii were found in 17.4% of 166 camels in titers of 1:25 (3 camels), 1:50 (18 camels). and > 1:500 (8 camels) using T. gondii tachyzoites. All 6 camels with N. caninum antibodies had no T. gondii antibodies in 1:4 dilution of serum, indicating specificity of the reaction. This is the first report of N. caninum prevalence in Egypt.