Effect of heart failure on catecholamine granule morphology and storage in chromaffin cells

One of the key mechanisms involved in sympathoexcitation in chronic heart failure (HF) is the activation of the adrenal glands. Impact of the elevated catecholamines on the hemodynamic parameters has been previously demonstrated. However, studies linking the structural effects of such overactivation with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not been previously reported. In this study, HF was induced in male Sprague-Dawley rats by ligation of the left coronary artery. Five weeks after surgery, cardiac function was assessed by ventricular hemodynamics. HF rats showed increased adrenal weight and adrenal catecholamine levels (norepinephrine, epinephrine and dopamine) compared with sham-operated rats. Rats with HF demonstrated increased small synaptic and dense core vesicle in splanchnic–adrenal synapses indicating trans-synaptic activation of catecholamine biosynthetic enzymes, increased endoplasmic reticulum and Golgi lumen width to meet the demand of increased catecholamine synthesis and release, and more mitochondria with dilated cristae and glycogen to accommodate for the increased energy demand for the increased biogenesis and exocytosis of catecholamines from the adrenal medulla. These findings suggest that increased trans-synaptic activation of the chromaffin cells within the adrenal medulla may lead to increased catecholamines in the circulation which in turn contributes to the enhanced neurohumoral drive, providing a unique mechanistic insight for enhanced catecholamine levels in plasma commonly observed in chronic HF condition

Impact of Chromogranin A deficiency on catecholamine storage, catecholamine granule morphology and chromaffin cell energy metabolism in vivo

Chromogranin A (CgA) is a prohormone and granulogenic factor in neuroendocrine tissues with a regulated secretory pathway. The impact of CgA depletion on secretory granule formation has been previously demonstrated in cell culture. However, studies linking the structural effects of CgA deficiency with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not previously been reported. Adrenomedullary content of the secreted adrenal catecholamines norepinephrine (NE) and epinephrine (EPI) was decreased 30–40 % in Chga-KO mice. Quantification of NE and EPI-storing dense core (DC) vesicles (DCV) revealed decreased DCV numbers in chromaffin cells in Chga-KO mice. For both cell types, the DCV diameter in Chga-KO mice was less (100–200 nm) than in WT mice (200–350 nm). The volume density of the vesicle and vesicle number was also lower in Chga-KO mice. Chga-KO mice showed an ~47 % increase in DCV/DC ratio, implying vesicle swelling due to increased osmotically active free catecholamines. Upon challenge with 2 U/kg insulin, there was a diminution in adrenomedullary EPI, no change in NE and a very large increase in the EPI and NE precursor dopamine (DA), consistent with increased catecholamine biosynthesis during prolonged secretion. We found dilated mitochondrial cristae, endoplasmic reticulum and Golgi complex, as well as increased synaptic mitochondria, synaptic vesicles and glycogen granules in Chga-KO mice compared to WT mice, suggesting that decreased granulogenesis and catecholamine storage in CgA-deficient mouse adrenal medulla is compensated by increased VMAT-dependent catecholamine update into storage vesicles, at the expense of enhanced energy expenditure by the chromaffin cell

Investigation of complete and incomplete fusion in 7^{7}Li+124^{124}Sn reaction around Coulomb barrier energies

The complete and incomplete fusion cross sections for $^{7}$Li+$^{124}$Sn reaction were measured using online and offline characteristic $\gamma$-ray detection techniques. The complete fusion (CF) cross sections at energies above the Coulomb barrier were found to be suppressed by $\sim$ 26 \% compared to the coupled channel calculations. This suppression observed in complete fusion cross sections is found to be commensurate with the measured total incomplete fusion (ICF) cross sections. There is a distinct feature observed in the ICF cross sections, i.e., $\textit{t}$-capture is found to be dominant than $\alpha$-capture at all the measured energies. A simultaneous explanation of complete, incomplete and total fusion (TF) data was also obtained from the calculations based on Continuum Discretized Coupled Channel method with short range imaginary potentials. The cross section ratios of CF/TF and ICF/TF obtained from the data as well as the calculations showed the dominance of ICF at below barrier energies and CF at above barrier energies.Comment: 9 pages, 8 figure

Ross syndrome: a case report

Ross syndrome is a rare partial dysautonomic syndrome of unknown aetiology, characterized by segmental hypo/ anhidrosis associated with Holmes-Adie syndrome (tonic pupil and hypo/areflexia). The hypohydrosis or anhydrosis is patchy initially, later it becomes segmental or diffuse. This is due to affection of postganglionic cholinergic parasympathetic and sympathetic fibers involvement. There are a very few cases (approximately 50) have been reported in the literature since its original description. Author report a 22 years old male with classical features of Ross syndrome

Van der Knaap disease

Van der Knaap disease is a rare form of leukodystrophy, phenotypically characterized by megalencephaly, early-onset ataxia, pyramidal features, cognitive impairment, with an autosomal recessive inheritence. MRI Brain shows T1 and FLAIR hypointense subcortical cysts in mostly temporal lobes and in fronto-parietal subcortical areas. Authors report a 20 yr. girl with typical features

Observation and analysis of spatiotemporal characteristics of surface ozone and carbon monoxide at multiple sites in the Kathmandu Valley, Nepal

Residents of the Kathmandu Valley experience severe particulate and gaseous air pollution throughout most of the year, even during much of the rainy season. The knowledge base for understanding the air pollution in the Kathmandu Valley was previously very limited but is improving rapidly due to several field measurement studies conducted in the last few years. Thus far, most analyses of observations in the Kathmandu Valley have been limited to short periods of time at single locations. This study extends the past studies by examining the spatial and temporal characteristics of two important gaseous air pollutants (CO and O3) based on simultaneous observations over a longer period at five locations within the valley and on its rim, including a supersite (at Bode in the valley center, 1345&thinsp;m above sea level) and four satellite sites: Paknajol (1380&thinsp;m&thinsp;a.s.l.) in the Kathmandu city center; Bhimdhunga (1522&thinsp;m&thinsp;a.s.l.), a mountain pass on the valley's western rim; Nagarkot (1901&thinsp;m&thinsp;a.s.l.), another mountain pass on the eastern rim; and Naikhandi (1233&thinsp;m&thinsp;a.s.l.), near the valley's only river outlet. CO and O3 mixing ratios were monitored from January to July 2013, along with other gases and aerosol particles by instruments deployed at the Bode supersite during the international air pollution measurement campaign SusKat-ABC (Sustainable Atmosphere for the Kathmandu Valley – endorsed by the Atmospheric Brown Clouds program of UNEP). The monitoring of O3 at Bode, Paknajol and Nagarkot as well as the CO monitoring at Bode were extended until March 2014 to investigate their variability over a complete annual cycle. Higher CO mixing ratios were found at Bode than at the outskirt sites (Bhimdhunga, Naikhandi and Nagarkot), and all sites except Nagarkot showed distinct diurnal cycles of CO mixing ratio, with morning peaks and daytime lows. Seasonally, CO was higher during premonsoon (March–May) season and winter (December–February) season than during monsoon season (June–September) and postmonsoon (October–November) season. This is primarily due to the emissions from brick industries, which are only operational during this period (January–April), as well as increased domestic heating during winter, and regional forest fires and agro-residue burning during the premonsoon season. It was lower during the monsoon due to rainfall, which reduces open burning activities within the valley and in the surrounding regions and thus reduces sources of CO. The meteorology of the valley also played a key role in determining the CO mixing ratios. The wind is calm and easterly in the shallow mixing layer, with a mixing layer height (MLH) of about 250&thinsp;m, during the night and early morning. The MLH slowly increases after sunrise and decreases in the afternoon. As a result, the westerly wind becomes active and reduces the mixing ratio during the daytime. Furthermore, there was evidence of an increase in the O3 mixing ratios in the Kathmandu Valley as a result of emissions in the Indo-Gangetic Plain (IGP) region, particularly from biomass burning including agro-residue burning. A top-down estimate of the CO emission flux was made by using the CO mixing ratio and mixing layer height measured at Bode. The estimated annual CO flux at Bode was 4.9&thinsp;µg&thinsp;m−2&thinsp;s−1, which is 2–14 times higher than that in widely used emission inventory databases (EDGAR HTAP, REAS and INTEX-B). This difference in CO flux between Bode and other emission databases likely arises from large uncertainties in both the top-down and bottom-up approaches to estimating the emission flux. The O3 mixing ratio was found to be highest during the premonsoon season at all sites, while the timing of the seasonal minimum varied across the sites. The daily maximum 8&thinsp;h average O3 exceeded the WHO recommended guideline of 50&thinsp;ppb on more days at the hilltop station of Nagarkot (159 out of 357 days) than at the urban valley bottom sites of Paknajol (132 out of 354 days) and Bode (102 out of 353 days), presumably due to the influence of free-tropospheric air at the high-altitude site (as also indicated by Putero et al., 2015, for the Paknajol site in the Kathmandu Valley) as well as to titration of O3 by fresh NOx emissions near the urban sites. More than 78&thinsp;% of the exceedance days were during the premonsoon period at all sites. The high O3 mixing ratio observed during the premonsoon period  is of a concern for human health and ecosystems, including agroecosystems in the Kathmandu Valley and surrounding regions.</p

Role of Reactive Oxygen Species in Hyperadrenergic Hypertension: Biochemical, Physiological, and Pharmacological Evidence From Targeted Ablation of the Chromogranin A (Chga) Gene

Oxidative stress, an excessive production of reactive oxygen species (ROS) outstripping antioxidant defense mechanisms, occurs in cardiovascular pathologies including hypertension. Here, we used biochemical, physiological, and pharmacological approaches to explore the role of derangements of catecholamines, ROS, and NO• in the development of a hyper-adrenergic model of hereditary hypertension: targeted ablation (knockout, KO) of chromogranin A (Chga) in the mouse