Hypothalamic And Peripheral Noradrenergic Responses To Changes In Baroreceptor Input In Conscious Rats With And Without Renal Nerves

Hypothalamic and peripheral noradrenergic systems have been implicated in baroreflex control of arteria pressure. However, the relationship between changes in the hypothalamic noradrenergic activity and changes in peripheral sympathetic activity is unclear. The first study examined this relationship in conscious Wistar rats following changes in baroreceptor input to the CNS produced by: (1) transection of aortic depressor nerve (ADN) (removal of specific baroreceptor input), (2) acute hypotension for 60 min produced by infusion of nitroprusside, and (3) acute hypertension for 60 min produced by infusion of phenylephrine. An index of norepinephrine (NE) turnover was used to assess the noradrenergic activity by measuring the decline in endogenous concentration of NE after inhibition of NE synthesis.;ADN transection, caused a significant elevation in arterial pressure, heart rate and NE turnover in the hypothalamus, midbrain, medulla, skeletal muscle, and kidney but not in the duodenum. Acute hypotension produced a reflex increase in heart rate and an increased NE turnover in the posterior hypothalamus (PH) and all peripheral organs examined (skeletal muscle, kidney and duodenum). Acute hypertension produced no significant changes in NE turnover in the hypothalamus or the peripheral organs examined.;Recent electrophysiological evidence suggests that baroreceptor information and afferent renal fibers may interact at the level of the hypothalamus. To determine the nature of such an interaction, the effect of renal denervation on hypothalamic and peripheral noradrenergic responses to changes in baroreceptor input were examined. Renal denervation normalized the elevated arterial pressure and increased NE turnover in the hypothalamus and skeletal muscle seen after ADN transection. In the acutely hypotensive group renal denervation abolished the increased NE turnover in PH but not in the peripheral organs. Renal denervation in the acutely hypertensive animals caused a significant decrease in NE turnover in the hypothalamus, unmasking an inhibitory influence of loaded baroreceptors .;In conclusion there is an inhibitory influence from the baroreceptor afferent and an excitatory influence from the renal afferents on the noradrenergic systems in the hypothalamus. Furthermore, hypothalamic and peripheral noradrenergic activity are not tightly linked, as dissociation of these two systems can be produced under certain conditions

Comparative Study of Double Pass Solar Air Heater with Solar Air Heater with Baffles & With Longitudinal Fins

Solar air heater is a most popular device in the space heating and industrial processes applications. But solar air heater has lower heat-transfer coefficient between the absorber plate and the air stream, which results in a lower thermal efficiency of the heater. The solar air heaters efficiency can be affected by various parameters such as collector length, number of channels, depth of channels, type of absorber plate, number and material of glass covers, air inlet temperature and air velocity. Comparative study of double pass solar air heater with fins, baffles and porous material’s effect has been carried out in this research study. Also, mass flow rate at the outlet of the double pass solar air heater in the metallic wiry sponge is significantly improve as compared to the other double pass solar air heater. So that, the maximum efficiency as been gained in the double pass solar air heater with metallic wiry sponge as compared to the other. DOI: 10.17762/ijritcc2321-8169.15056

A Review to Enhance the Efficiency of Double Pass Solar Air Heater

Solar air heater is a most popular device in the space heating and industrial processes applications. But solar air heater has lower heat-transfer coefficient between the absorber plate and the air stream, which results in a lower thermal efficiency of the heater. The solar air heaters efficiency can be affected by various parameters such as collector length, number of channels, depth of channels, type of absorber plate, number and material of glass covers, air inlet temperature and air velocity. The effect of fins, Baffles and porous media on double pass solar air heater will measured by this research study. This aim is to analyze the thermal efficiency of double pass solar air heater and measured the effect of different type of media on the efficiency of it. The effects of major parameters temperature difference, air velocity, pressure difference, mass flow rate of the air has been observed for these perform study. DOI: 10.17762/ijritcc2321-8169.15025

Kinetic and Thermodynamic Approaches for the Efficient Formation of Mechanical Bonds

Among the growing collection of molecular systems under consideration for nanoscale device applications, mechanically interlocked compounds derived from electrochemically switchable bistable [2]rotaxanes and [2]catenanes show great promise. These systems demonstrate dynamic, relative movements between their components, such as shuttling and circumrotation, enabling them to serve as stimuli-responsive switches operated via reversible, electrochemical oxidation−reduction rather than through the addition of chemical reagents. Investigations into these systems have been intense for a number of years, yet limitations associated with their synthesis have hindered incorporation of their mechanical bonds into more complex architectures and functional materials. We have recently addressed this challenge by developing new template-directed synthetic protocols, operating under both kinetic and thermodynamic control, for the preparation of bistable rotaxanes and catenanes. These methodologies are compatible with the molecular recognition between the π-electron-accepting cyclobis(paraquat-p-phenylene) (CBPQT4+) host and complementary π-electron-donating guests. The procedures that operate under kinetic control rely on mild chemical transformations to attach bulky stoppering groups or perform macrocyclizations without disrupting the host−guest binding of the rotaxane or catenane precursors. Alternatively, the protocols that operate under thermodynamic control utilize a reversible ring-opening reaction of the CBPQT4+ ring, providing a pathway for two cyclic starting materials to thread one another to form more thermodynamically stable catenaned products. These complementary pathways generate bistable rotaxanes and catenanes in high yields, simplify mechanical bond formation in these systems, and eliminate the requirement that the mechanical bonds be introduced into the molecular structure in the final step of the synthesis. These new methods have already been put into practice to prepare previously unavailable rotaxane architectures and novel complex materials. Furthermore, the potential for utilizing mechanically interlocked architectures as device components capable of information storage, the delivery of therapeutic agents, or other desirable functions has increased significantly as a result of the development of these improved synthetic protocols

Neurogenic Hypertension Mediated Mitochondrial Abnormality Leads to Cardiomyopathy: Contribution of UPR mt and Norepinephrine-miR- 18a-5p-HIF-1α Axis

Aims: Hypertension increases the risk of heart disease. Hallmark features of hypertensive heart disease is sympathoexcitation and cardiac mitochondrial abnormality. However, the molecular mechanisms for specifically neurally mediated mitochondrial abnormality and subsequent cardiac dysfunction are unclear. We hypothesized that enhanced sympatho-excitation to the heart elicits cardiac miR-18a-5p/HIF-1α and mitochondrial unfolded protein response (UPRmt) signaling that lead to mitochondrial abnormalities and consequent pathological cardiac remodeling. Methods and Results: Using a model of neurogenic hypertension (NG-HTN), induced by intracerebroventricular (ICV) infusion of Ang II (NG-HTN; 20 ng/min, 14 days, 0.5 μl/h, or Saline; Control, 0.9%) through osmotic mini-pumps in Sprague-Dawley rats (250-300 g), we attempted to identify a link between sympathoexcitation (norepinephrine; NE), miRNA and HIF-1α signaling and UPRmt to produce mitochondrial abnormalities resulting in cardiomyopathy. Cardiac remodeling, mitochondrial abnormality, and miRNA/HIF-1α signaling were assessed using histology, immunocytochemistry, electron microscopy, Western blotting or RT-qPCR. NG-HTN demonstrated increased sympatho-excitation with concomitant reduction in UPRmt, miRNA-18a-5p and increased level of HIF-1α in the heart. Our in silico analysis indicated that miR-18a-5p targets HIF-1α. Direct effects of NE on miRNA/HIF-1α signaling and mitochondrial abnormality examined using H9c2 rat cardiomyocytes showed NE reduces miR-18a-5p but increases HIF-1α. Electron microscopy revealed cardiac mitochondrial abnormality in NG-HTN, linked with hypertrophic cardiomyopathy and fibrosis. Mitochondrial unfolded protein response was decreased in NG-HTN indicating mitochondrial proteinopathy and proteotoxic stress, associated with increased mito-ROS and decreased mitochondrial membrane potential (ΔΨm), and oxidative phosphorylation. Further, there was reduced cardiac mitochondrial biogenesis and fusion, but increased mitochondrial fission, coupled with mitochondrial impaired TIM-TOM transport and UPRmt. Direct effects of NE on H9c2 rat cardiomyocytes also showed cardiomyocyte hypertrophy, increased mitochondrial ROS generation, and UPRmt corroborating the in vivo data. Conclusion: In conclusion, enhanced sympatho-excitation suppress miR-18a-5p/HIF-1α signaling and increased mitochondrial stress proteotoxicity, decreased UPRmt leading to decreased mitochondrial dynamics/OXPHOS/ΔΨm and ROS generation. Taken together, these results suggest that ROS induced mitochondrial transition pore opening activates pro-hypertrophy/fibrosis/inflammatory factors that induce pathological cardiac hypertrophy and fibrosis commonly observed in NG-HTN

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

DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF IVERMECTIN AND CLORSULON IN IVERCAM INJECTION

A precise, simple, accurate and selective method was developed and validate for estimation of Ivermectin and Clorsulon in Ivercam injection, Reversed phase high performance liquid chromatographic (RP-HPLC) method was developed for routine quantification of Ivermectin and Clorsulon in laboratory prepared mixtures as well as in combined dosage form. Chromatographic separation was achieved on a BDS hypersil C18 (5μ, 250 x 4.6 mm) utilizing mobile phase of filtered and degassed mixture of 60 phosphate buffer (pH 5.5 adjusted with 1% O-phosphoric acid) and Methanol (60:40 v/v) at a flow rate of 1 mL/min with UV detection at 234 nm. The method has been validated for linearity, accuracy and precision. In RP-HPLC method, the calibration graphs were linear in the concentration range of 2.5-7.5 μg/ml for Ivermectin and 25-75 μg/ml for Clorsulon with percentage recoveries of 100.34 % and 99.76% for Ivermectin and Clorsulon respectively. Conclusion: The results obtained by RP-HPLC methods are rapid, accurate and precise. Therefore proposed method can be used for routine analysis of Clorsulon and Ivermectin in injection

Enhanced Central Sympathetic Tone Induces Heart Failure with Preserved Ejection Fraction (HFpEF) in Rats

Heart failure with preserved ejection fraction (HFpEF) is a heterogenous clinical syndrome characterized by diastolic dysfunction, concentric cardiac left ventricular (LV) hypertrophy, and myocardial fibrosis with preserved systolic function. However, the underlying mechanisms of HFpEF are not clear. We hypothesize that an enhanced central sympathetic drive is sufficient to induce LV dysfunction and HFpEF in rats. Male Sprague-Dawley rats were subjected to central infusion of either saline controls (saline) or angiotensin II (Ang II, 20 ng/min, i.c.v) via osmotic mini-pumps for 14 days to elicit enhanced sympathetic drive. Echocardiography and invasive cardiac catheterization were used to measure systolic and diastolic functions. Mean arterial pressure, heart rate, left ventricular end-diastolic pressure (LVEDP), and ± dP/dt changes in responses to isoproterenol (0.5 μg/kg, iv) were measured. Central infusion of Ang II resulted in increased sympatho-excitation with a consequent increase in blood pressure. Although the ejection fraction was comparable between the groups, there was a decrease in the E/A ratio (saline: 1.5 ± 0.2 vs Ang II: 1.2 ± 0.1). LVEDP was significantly increased in the Ang II-treated group (saline: 1.8 ± 0.2 vs Ang II: 4.6 ± 0.5). The increase in +dP/dt to isoproterenol was not significantly different between the groups, but the response in -dP/dt was significantly lower in Ang II-infused rats (saline: 11,765 ± 708 mmHg/s vs Ang II: 8,581 ± 661). Ang II-infused rats demonstrated an increased heart to body weight ratio, cardiomyocyte hypertrophy, and fibrosis. There were elevated levels of atrial natriuretic peptide and interleukin-6 in the Ang II-infused group. In conclusion, central infusion of Ang II in rats induces sympatho-excitation with concurrent diastolic dysfunction, pathological cardiac concentric hypertrophy, and cardiac fibrosis. This novel model of centrally mediated sympatho-excitation demonstrates characteristic diastolic dysfunction in rats, representing a potentially useful preclinical murine model of HFpEF to investigate various altered underlying mechanisms during HFpEF in future studie

A toxicological review of Bhallataka

Bhallataka (Semecarpus anacardium Linn.) is mentioned in the group of Sthavar vanaspatika Visha in different Ayurvedic text book’s also it is irritant organic vegetable poison. All the parts are poisonous mostly seeds are hazadous to human, due to its irritant property. The Bhallataka nut contain bhilwanol and semecarpal as toxic ingredient show some medicinal properties. By its hot potency it has some local action like Sphotjananam (Ushna-Virya). An number of Ayurvedic formulation includes this drug after the proper Shodhana (purification) as in judicious use of Asuddha (impure) Bhallataka may results in toxic effect like burning sensation of skin blister formation, ulcer and so on. Treatment of toxic effect of Bhallataka is described various texts of Ayurveda. Modern toxicology also describes manifestation, treatment, autopsy finding and medico legal aspect of semecarpus anacardium linn