Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy

Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy.BackgroundRenal urinary concentration is associated with enhanced expression of rBSC1, a rat sodium cotransporter, in the thick ascending limb of Henle. Increased expression of rBSC1 was reported recently in nephrogenic diabetes insipidus induced by lithium chloride (Li nephropathy). However, the pathophysiological implication of altered rBSC1 expression has not yet been investigated.MethodsLi nephropathy was induced in rats by an oral administration of 40 mmol lithium/kg dry food. In rats with reduced urinary osmolality to less than 300 mOsm/kg H2O, we examined the expression of rBSC1 mRNA and protein, plasma arginine vasopressin (AVP) and RNA expression of kidney-specific water channel, aquaporin-2 (AQP2), of collecting ducts. Rats with Li nephropathy were treated with furosemide (3 mg/kg body weight), which blocks the activity of rBSC1, and changes in urine concentration, plasma AVP, medullary accumulation of Li ions, and apical AQP2 expression were determined.ResultsRats with Li nephropathy showed increased rBSC1 RNA and protein expression and reduced AQP2 RNA. In these rats, furosemide, which induces dilution of urine and polyuria in normal rats, resulted in a progressive and significant rise in urine osmolality from 167 ± 11 (mean ± SD) at baseline to 450 ± 45 mOsm/kg H2O at three hours after administration, and significant oliguria. In the same rats, plasma AVP decreased significantly from 5.7 to 3.0 pg/mL. In addition, recovery of apical AQP2 expression was noted in a proportion of epithelial cells of the collecting ducts. Although Li+ in the renal medulla was slightly lower in rats with Li nephropathy treated with furosemide, statistical significance was not achieved.ConclusionsOur results suggest that dehydration or high plasma AVP results in an enhanced rBSC1 expression in Li nephropathy, and that rBSC1 expression is closely associated with the adverse effects of Li ions on collecting duct function

Molecular Analysis of Neorickettsia risticii in Adult Aquatic Insects in Pennsylvania, in Horses Infected by Ingestion of Insects, and Isolated in Cell Culture

Upon ingestion of adult aquatic insects, horses developed clinical signs of Potomac horse fever, and Neorickettsia risticii was isolated from the blood. 16S rRNA and 51-kDa antigen gene sequences from blood, isolates, and caddis flies fed to the horses were identical, proving oral transmission of N. risticii from caddis flies to horses

Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut

The mechanism to maintain homeostasis of the gut microbiota remains largely unknown despite its critical role in the body defense. In the intestines of mice with deficiency of activation-induced cytidine deaminase (AID), the absence of hypermutated IgA is partially compensated for by the presence of large amounts of unmutated IgM and normal expression levels of defensins and angiogenins. We show here a predominant and persistent expansion of segmented filamentous bacteria throughout the small intestine of AID(–/–) mice. Reconstitution of lamina propria IgA production in AID(–/–) mice recovered the normal composition of gut flora and abolished the local and systemic activation of the immune system. The results indicate that secretions of IgAs rather than innate defense peptides are critical to regulation of commensal bacterial flora and that the segmented filamentous bacteria antigens are strong stimuli of the mucosal immune system

Fatal Tickborne Phlebovirus Infection in Captive Cheetahs, Japan

Two captive cheetahs from a zoo in Japan died of a severe fever with thrombocytopenia syndrome?like illness. Severe fever with thrombocytopenia syndrome virus, an endemic tickborne phlebovirus, was detected systemically with secretion of infectious viruses into the saliva. These cases highlight the risk for exposure of captive animals to endemic arthropodborne pathogens

Antenatal Growth, Gestational Age, Birth, Enteral Feeding, and Blood Citrulline Levels in Very Low Birth Weight Infants

Early enteral nutrition using reliable biomarkers of intestinal function must be established to improve neurodevelopmental outcomes in very low birth weight infants (VLBWIs). Serum citrulline levels reflect the intestinal function in adults. To elucidate the relationship among antenatal growth, postnatal enteral nutrition, and blood citrulline levels, a retrospective single-center observational study was conducted on 248 VLBWIs born between April 2014 and March 2021. A mixed effect model and post hoc simple slope analysis were used to estimate the correlations between clinical variables and citrulline levels at Early (day 5.1) and Late (day 24.3) postnatal ages. Greater gestational age, birth weight, and amount of enteral nutrition at the time of blood sampling were associated with lower citrulline levels at the Early postnatal age and higher citrulline levels at the Late postnatal age. Provided that Early citrulline levels predominantly reflect the consequence of antenatal citrulline metabolism, it is suggested that fetal growth and maturation are likely to promote citrulline catabolism in utero and its synthesis after birth. With additional insights into the temporal transition point wherein the maturation-dependent balance of citrulline metabolism shifts from catabolism-dominant to synthesis-dominant, citrulline emerges as a potential biomarker for assessing intestinal function and gastrointestinal disorders

Novel SPEG variants in a neonate with severe dilated cardiomyopathy and relatively mild hypotonia

Abstract Striated muscle preferentially expressed protein kinase (SPEG) variants have been reported to cause centronuclear myopathy associated with cardiac diseases. The severity of skeletal muscle symptoms and cardiac symptoms are presumably related to the location of the variant. Here, we report novel SPEG compound heterozygous pathological variants in a neonate with severe dilated cardiomyopathy and relatively mild hypotonia. This report expands the genotype-phenotype correlations of patients with SPEG variants