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Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle. Am J Physiol Renal Physiol 286: F1144-F1153, 2004. First published February 10, 2004; 10.1152/ajprenal. 00236.2003.--Pharmacological interruption of angiotensin II type 1 (A[T.sub.1] receptor signaling during nephrogenesis in rats perturbs renal tubular development. Perturbed tubulogenesis may contribute to longterm impairment of urinary concentrating ability, which is the main functional irreversible defect. The aim of this study was to further characterize tubular developmental deficits in neonatal rats, focusing on the thick ascending limb of Henle (TALH), known to undergo profound developmental changes and to be involved in urine-concentrating mechanisms. We have carried out immunohistochemistry and Western immunoblotting using antibodies directed against the major histocompatibility complex class II (MHC II) molecule and different TALH-specific markers, namely, cyclooxygenase-2 (COX-2), TammHorsfall glycoprotein (THP), and the bumetanide-sensitive [Na.sup.+]-[K.sup.+]2 [Cl.sup.-] cotransporter (BSC-1/NKCC2). Immunohistochemistry demonstrated expression of MHC II, COX-2, THP, and BSC-1/NKCC2 proteins in normally developing TALH cells. The A[T.sub.1]Freceptor antagonist losartan abolished MHC II expression exclusively in the developing TALH cells. Increased expression of COX-2 and THP was observed in the TALH cells of losartan-treated rats. Western immunoblotting confirmed increases in cortical and medullary COX-2 and THP abundance and revealed a decrease in cortical BSC-1/NKCC2 abundance in response to losartan treatment. We conclude that neonatal losartan treatment causes significant changes in the phenotype of the developing TALH in the rat. renal development; A[T.sub.1] receptor blockade; major histocompatibility complex class II molecule; cyclooxygenase-2; Tamm-Horsfall glycoprotein; bumetanide-sensitive sodium-potassium-chloride cotransporter

Aims: There is an urgent need to explore the impact of the COVID-19 pandemic on adolescent mental health and health behaviours. To date, there are no such studies on Swedish adolescents. As COVID-19 emerged in the middle of our ongoing 2-year follow-up examination of the Study of Adolescence Resilience and Stress, we had the unique opportunity to use the corona outbreak as a 'natural experiment' to study the impact of COVID-19 on 15-year-old adolescents in Sweden. Methods: Adolescents (baseline age 13.6±0.4 years) were recruited from schools in western Sweden (during the COVID-19 outbreak schools were kept open for those under 16 years of age). The COVID-19 pandemic reached Sweden on 31 January 2020. A total of 1316 adolescents answered the 2-year follow-up survey before (unexposed to COVID-19 pandemic, controls) and 584 after 1 February 2020 (COVID19-exposed). Data on stress, psychosomatic symptoms, happiness, relationships with parents and peers, school and health behaviours were collected. Results: Adolescents reported higher levels of stress and psychosomatic symptoms and lower levels of happiness at follow-up compared to baseline. These changes occurred to a similar extent in both the control and COVID-19-exposed groups. Likewise, the COVID-19-exposed group showed no deterioration in peer relations or relations with parents versus controls. We did not find any significant differences between groups regarding sleep duration and physical activity. Conclusions: Swedish adolescents exposed to COVID-19 during most of 2020 showed no differences in longitudinal changes in mental health, relationships with parents and peers, and health behaviours compared to those not exposed to COVID-19. [ABSTRACT FROM AUTHOR]

Measuring the amount of plasma free metanephrines appears to be the best diagnostic test for identifying patients who have an adrenal gland tumor called a pheochromocytoma. This was the conclusion of researchers who measured plasma free metanephrines, plasma catecholamines, urinary catecholamines, urinary total and fractionated metanephrines, and urinary vanillylmandelic acid in a study of 858 patients., Context Diagnosis of pheochromocytoma depends on biochemical evidence of catecholamine production by the tumor. However, the best test to establish the diagnosis has not been determined. Objective To determine the biochemical test or combination of tests that provides the best method for diagnosis of pheochromocytoma. Design, Setting, and Participants Multicenter cohort study of patients tested for pheochromocytoma at 4 referral centers between 1994 and 2001. The analysis included 214 patients in whom the diagnosis of pheochromocytoma was confirmed and 644 patients who were determined to not have the tumor. Main Outcome Measures Test sensitivity and specificity, receiver operating characteristic curves, and positive and negative predictive values at different pretest prevalences using plasma free metanephrines, plasma catecholamines, urinary catecholamines, urinary total and fractionated metanephrines, and urinary vanillylmandelic acid. Results Sensitivities of plasma free metanephrines (99% [95% confidence interval (CI), 96%-100%]) and urinary fractionated metanephrines (97% [95% CI, 92%-99%]) were higher than those for plasma catecholamines (84% [95% CI, 78%-89%]), urinary catecholamines (86% [95% CI, 80%-91 %]), urinary total metanephrines (77% [95% CI, 68%-85%]), and urinary vanillylmandelic acid (64% 1195% CI, 55%-71 %]). Specificity was highest for urinary vanillylmandelic acid (95% [95% CI, 93%-97%]) and urinary total metanephrines (93% [95% CI, 89%-97%]); intermediate for plasma free metanephrines (89% [95% CI, 87%-92%]), urinary catecholamines (88% [95% Cl, 85%91%]), and plasma catecholamines (81 % [95% CI, 78%-84%]); and lowest for urinary fractionated metanephrines (69% [95% Cl, 64%-72%]). Sensitivity and specificity values at different upper reference limits were highest for plasma free metanephrines using receiver operating characteristic curves. Combining different tests did not improve the diagnostic yield beyond that of a sin gle test of plasma free metanephrines. Conclusion Plasma free metanephrines provide the best test for excluding or confirming pheochromocytoma and should be the test of first choice for diagnosis of the tumor.

The relationship between norepinephrine (NE) release and spillover in the human heart, kidneys and forearm was investigated by monitoring the specific activities of exogenous tritium-labeled NE in plasma and interstitial fluid. Results reveal that NE spillover significantly underestimates NE release. In the kidneys, NE release is thrice the spillover rate, in skeletal muscles release is 12 times the spillover while in the heart it is more than 20 times the spillover.

The effects of neonatal administration on the ability of the rat kidneys to secrete acid and acidify urine were investigated using metabolic balance studies and clearance experiments in anesthetized adult rats which received enalapril from day 5 to 24. Results reveal that the kidney tubules of these rats have impaired urinary concentrating function but intact acid excretion and urinary acidification functions.

Research shows that cardiac tyrosine hydroxylation is boosted by exercise in human beings. The sympathetic nervous system releases more of the biochemical cardiac norepinephrine than dihydroxyphenylalanine following stimulation from the enzyme tyrosine hydroxylase. The turnover rate of the neurotransmitter norepinephrine and related levels in tyrosine hydroxylation are considered.

The mechanism underlying the cardiorenal epinephrine release was analyzed through isotope-dilution method which was used on patients with congestive heart failure and hypertension and healthy individuals as the control variable. Results have shown that under baseline conditions, cardiac release of Epi in congestive heart patients was evident through (3H)Epi dilution. A decrease in cardiorenal fractional extractions of epinephrine was noted following neuronal blockade.

A study was conducted on potassium and sodium balance during dietary sodium loading and restriction in enalapril-treated adult Wistar rats. The rats exhibited sodium retention during loading and normal adaptation and transient renal potassium wastage during restriction. Enalapril-treated rats also exhibited reduced renal sodium and potassium handling as well as weak urinary concentrating ability.

Researchers have been able to simultaneously assess arm and leg norepinephrine (NE) spillover related to 100 g tissue and total limb weight by using state-state infusion of (H)NE and body composition determination by dual-energy X-ray absorptiometry-scan. It was found that fractional extraction of (H)NE was similar in arm and leg. However, there was a differentiated NE spillover within skeletal muscle, with NE spillover being lower from leg than from arm. This may be the result of a combination of lower sympathetic outflow and higher NE neuronal uptake.

A study carried out in swine to estimate hepatomesentric release and removal of norepinephrine (NE), found that sampling portal, arterial and hepatic venous plasma is essential for the complete examination of NE spillover from hepatomesenteric organs as a reliable index of sympathetic outflow. The net hepatomesentric spillover estimated using arterial and hepatic venous measurements is exceeded by the sum of mesentric and hepatic NE spillover. The study provides a method, involving the calculation of both mesentric and hepatic NE spillover, to evaluate sympathetic nervous function in conditions such as circulatory shock.

A study on metabolism of concentration and catecholamines using anesthetized swine reveals important role of mesenteric organs in the production of dopamine and norepinephrine metabolism. Production of mesenteric organs does not exceed removal of dihydroxyphenylacetic acid and the concentration of homovanillic acid by the liver. This results in more hepatic than renal elimination of the metabolites of the body, besides implying an underestimation of dopamine production by mesenteric organs.

A study involved the measurement of the operational myocardial capillary diffusion capacity in relation to the permeability surface area product (PS) for Cr-EDTA and vitamin-B12 in isolated beating Langendorff-perfused rat hearts, after previous exposure to long-standing pressure and volume overload. The overload causes a cardiac hypertrophy that was formed to almost the same extent in both experimental settings. Contrary to previous morphometric estimations in pressure overload hypertrophy, myocardial capillary diffusion capacity was well maintained. In volume overloaded cardiac hypertroply, the myocardial capillary diffusion capacity was well maintained.

Abstract We have quantitatively analyzed the confocal spectra of colloidal quantum dots (QDs) in rat endothelial progenitor cells (EPCs) by using Leica TCS SP5 Confocal Microscopy System. Comparison of the confocal spectra of QDs located inside and outside EPCs revealed that the interaction between the QDs and EPCs effectively reduces the radius of the exciton confinement inside the QDs so that the excitonic energy increases and the QD fluorescence peak blueshifts. Furthermore, the EPC environment surrounding the QDs shields the QDs so that the excitation of the QDs inside the cells is relatively weak, whereas the QDs outside the cells can be highly excited. At high excitations, the occupation of the ground excitonic state in the QD outside the cells becomes saturated and high-energy states excited, resulting in a large relaxation energy and a broad fluorescence peak. This permits, in concept, to use QD biomarkers to monitor EPCs by characterizing QD fluorescence spectra.