The epithelial sodium channel in inflammation and blood pressure modulation

A major regulator of blood pressure and volume homeostasis in the kidney is the epithelial sodium channel (ENaC). ENaC is composed of alpha(α)/beta(β)/gamma(γ) or delta(δ)/beta(β)/gamma(γ) subunits. The δ subunit is functional in the guinea pig, but not in routinely used experimental rodent models including rat or mouse, and thus remains the least understood of the four subunits. While the δ subunit is poorly expressed in the human kidney, we recently found that its gene variants are associated with blood pressure and kidney function. The δ subunit is expressed in the human vasculature where it may influence vascular function. Moreover, we recently found that the δ subunit is also expressed human antigen presenting cells (APCs). Our studies indicate that extracellular Na+ enters APCs via ENaC leading to inflammation and salt-induced hypertension. In this review, we highlight recent findings on the role of extra-renal ENaC in inflammation, vascular dysfunction, and blood pressure modulation. Targeting extra-renal ENaC may provide new drug therapies for salt-induced hypertension

Breast Cancer: Impact of Modifiable and Non-Modifiable Risk Factors Among Premenopausal Women of Karachi, Sindh

Objective: The goal of present study was to probe the interplay between modifiable and non-modifiable factors and breast cancer (BC) risk. Methodology: Two hundred and twenty-eight (228) BC cases and 503 healthy volunteers with 20-45years of age without history of BC were recruited from tertiary hospitals located in Karachi, a metropolitan city ofPakistan. Major risk factors for the BC were evaluated using pretested self-structured questionnaire. Results: The adjusted regression analysis showed that Balouchi (OR=12.93, 95%CI=4.26-39.17) and Sindhi (OR=9.41, 95%CI=4.72-18.77) ethnicity, familial history of BC (OR=1.83, 95%CI=1.16-2.91), low socioeconomic status (OR=26.81, 95%CI=17.56-40.94), marital age >30yrs (OR=20.99, 95%CI=4.15-106.24),hormone replacement therapy (OR=1.95, 95%CI=1.03-3.69), being obese (OR=1.589, 95%CI=1.03-2.46),high waist-to-Hip ratio (WHR) (OR=2.69, 95%CI=1.67-4.32), apple shape body (OR=2.62, 95%CI=1.63-4.21), consanguineous marriages (OR=1.62, 95% CI=1.15-2.29) and sun exposure <1 hr/day (OR=7.56,95%CI=3.002-19.04), daily intake of beef (OR = 1.544, 95%CI=1.004-2.373), dry fruits (OR=1.922,95%CI=1.233-2.996), rice (OR= 2.412, 95%CI=1.17-4.973), tea and coffee (OR=2.299, 95%CI=1.246-4.24)and less consumption of milk (OR=1.942, 95%CI=1.344-2.807) and fruits (OR=2.952, 95%CI=1.505-5.792) were increased the BC risk among premenopausal women. Conversely, first pregnancy <24yrs (OR=0.53,95%CI=0.33-0.85), WHR <0.85 (OR=0.296, 95%CI=0.15-0.59), avocado body shape (OR=0.31,95%CI=0.16-0.61), excessive chicken (OR=0.403, 95%CI=0.206-0.791) and eggs (OR=0.479, 95CI=0.304-0.755) consumption were considered a protective factor. Conclusion: Ethnicity, SES, marital age, HRT, breast cancer family history, overweight and obesity,intermarriages and sun exposure may be the major risk factors for BC among premenopausal women of Sindh, Pakistan. Diet may also play a role in developing BC

Investigation of the cardiac depressant effect of Caralluma tuberculate N.E.Br on isolated rabbit heart

Purpose: To investigate the histopathological and cardiac depressant effect of the aqueous methanol extract of Caralluma tuberculata N.E. Br (AMECT) (family: Asclepiadaceae)’ and to determine if there is a scientific basis for its cardiovascular diseases-related folkloric use. Methods: The effect of AMECT in different concentrations ranging from 0.00001 to 1.0 mg/mL were evaluated in isolated perfused rabbit heart to assess their effect on the force of contraction and heart rate using Langendorff’s apparatus. Atropine and adrenaline were used to identify the underlying mechanism of response produced by AMECT. The extract was studied for its possible mechanism in the absence and presence of atropine and adrenaline. In addition, sub-chronic toxicity and histopathological study of heart tissues in rats were assessed by administering 500 mg/kg of extract. Results: At all concentrations, AMECT produced significant (p &lt; 0.001) negative ionotropic and negative chronotropic effects. The most significant effect was observed at 0.001 mg/mL and higher concentrations hence 0.001 mg/mL was selected for further studies. Pre-incubation with atropine did not significantly inhibit the effects of AMECT. However, AMECT significantly (p &lt; 0.01) blocked the cardiac stimulant effect of adrenaline. In the histopathological studies, AMECT did not produce any significant cellular changes or signs of toxicity in the sub-chronic toxicity study. Conclusion: The cardiac-depressant responses of AMECT may involve the β-adrenergic receptors in the myocardium of isolated rabbit heart thus confirming the rationale for its use in ethnomedicine for cardiac diseases

Dynamic Evaluation of Desiccant Dehumidification Evaporative Cooling Options for Greenhouse Air-Conditioning Application in Multan (Pakistan)

This study provides insights into the feasibility of a desiccant dehumidification-based Maisotsenko cycle evaporative cooling (M-DAC) system for greenhouse air-conditioning application. Conventional cooling techniques include direct evaporative cooling, refrigeration systems, and passive/active ventilation. which are commonly used in Pakistan; however, they are either not feasible due to their energy cost, or they cannot efficiently provide an optimum microclimate depending on the regions, the growing seasons, and the crop being cultivated. The M-DAC system was therefore proposed and evaluated as an alternative solution for air conditioning to achieve optimum levels of vapor pressure deficit (VPD) for greenhouse crop production. The objective of this study was to investigate the thermodynamic performance of the proposed system from the viewpoints of the temperature gradient, relative humidity level, VPD, and dehumidification gradient. Results showed that the standalone desiccant air-conditioning (DAC) system created maximum dehumidification gradient (i.e., 16.8 g/kg) and maximum temperature gradient (i.e., 8.4 °C) at 24.3 g/kg and 38.6 °C ambient air conditions, respectively. The DAC coupled with a heat exchanger (DAC+HX) created a temperature gradient nearly equal to ambient air conditions, which is not in the optimal range for greenhouse growing conditions. Analysis of the M-DAC system showed that a maximum air temperature gradient, i.e., 21.9 °C at 39.2 °C ambient air condition, can be achieved, and is considered optimal for most greenhouse crops. Results were validated with two microclimate models (OptDeg and Cft) by taking into account the optimality of VPD at different growth stages of tomato plants. This study suggests that the M-DAC system is a feasible method to be considered as an efficient solution for greenhouse air-conditioning under the climate conditions of Multan (Pakistan)

Juglone in Oxidative Stress and Cell Signaling

Juglone (5-hydroxyl-1,4-naphthoquinone) is a phenolic compound found in walnuts. Because of the antioxidant capacities of phenolic compounds, juglone may serve to combat oxidative stress, thereby protecting against the development of various diseases and aging processes. However, being a quinone molecule, juglone could also act as a redox cycling agent and produce reactive oxygen species. Such prooxidant properties of juglone may confer health effects, such as by killing cancer cells. Further, recent studies revealed that juglone influences cell signaling. Notably, juglone is an inhibitor of Pin1 (peptidyl-prolyl cis/trans isomerase) that could regulate phosphorylation of Tau, implicating potential effects of juglone in Alzheimer&rsquo;s disease. Juglone also activates mitogen-activated protein kinases that could promote cell survival, thereby protecting against conditions such as cardiac injury. This review describes recent advances in the understanding of the effects and roles of juglone in oxidative stress and cell signaling

Dynamics of novel exact soliton solutions to Stochastic Chiral Nonlinear Schrödinger Equation

The core objective of this study is to explore the some novel stochastic solutions. For this purpose, we consider the stochastic (2+1)-dimensional Chiral nonlinear Schrödinger equation (2D-SCNLSE) which is derived with multiplicative noise in the Itô sense. To achieve novel stochastic solutions, we employ two modified techniques as modified generalized exponential rational function method (mGERFM) and the modified rational sine-cosine and sinh-cosh methods. We extract exponential, periodic, bright, dark, and singular in single and combo forms. Due to the applications of the Chiral nonlinear Schrödinger equation in soliton theory, these solutions are extremely viable to exemplify some sensational complicated physical phenomena and applicable in diversified fields of applied sciences. This study enhances the theory of Itô calculus by directly performing it into analytical approaches for the solution of differential equations. To examine the impact of multiplicative noise on the results, several graphs have been plotted. We comprehend that the noise destroys the symmetry of the solutions of adopted model. The evaluated achievements suggested that the proposed methods are categorical, efficacious, reliable, and robust and can be the best way to handle other complex equations arising in applied sciences

Blood pressure-lowering and cardiovascular effects of plumbagin in rats: An insight into the underlying mechanisms

Background: Plumbagin, a natural phenolic compound is investigated for response against blood pressure and vascular reactivity. Methodology: Blood pressure lowering effects were observed by in-vivo invasive evaluation in normotensive rats, and in-vitro experimentation to measure changes of tension in isolated rat aorta and contractility in atria. Results: The percentage decrease in mean arterial pressure (MAP) observed with plumbagin intravenously at doses of 0.1, 0.5, 1, 5, 10 ​μg/kg in normotensive rats was 7.16 ​± ​2.35, 15.5 ​± ​5.62, 19.5 ​± ​5.27, 26 ​± ​6.67, 34.33 ​± ​8.80, respectively. Plumbagin exerted vasorelaxant effects in rat aorta, unaffected by the removal of vascular endothelium, and L-NAME and methylene blue pretreatment. Plumbagin completely inhibited phenylephrine (1 ​μM) and High K+ (80 ​mM) induced contractions. Similar to a Ca+2 channel antagonist, plumbagin caused a rightward shift in the Ca+2 concentration-response-curves (CRCs), resembling nifedipine. Pre-incubation with plumbagin, significantly suppressed contractions induced by phenylephrine in Ca+2-free medium via disrupting Ca+2 release from intracellular stores. No change in vasorelaxant response was observed with the addition of potassium channel blockers, TEA and BaCl2. In rat atrial strips, plumbagin exerted significant negative inotropic and chronotropic effects. No significant change was observed with atropine and atenolol pretreatment, so the effect appeared independent of muscarinic and beta-adrenergic receptors. Conclusion: This study suggests the blood pressure lowering effects of plumbagin. That could be contributed by a decrease in vascular resistance via calcium antagonism, interferences in calcium efflux, and depressive effects on the rate and force of cardiac contraction. Further studies would be necessary to probe deeper into the underlying mechanisms

Effect of voltage-gated sodium channels blockers on motility and viability of human sperm in vitro

Objective: To test the effect of voltage-gated sodium channels (VGSCs) blockers on the motility and viability of human sperm in-vitro and to evaluate the tested compounds as potential contact spermicidal.Methods: Sperm samples were obtained from healthy nonsmoking volunteers of age 25-30 years who had not taken any drug 3 months before and during the course of the study. The effect of VGSCs blockers evaluated from two pharmacological classes including antiarrhythmic (amiodarone, procainamide and disopyramide) and antiepileptic (carbamazepine, oxcarbazepine, phenytoin, and lamotrigine) drugs. They were tested on the in-vitro motility and viability of human sperm using Computer Assisted Semen Analyzer.Results: All tested drugs except oxcarbazepine showed dose dependent inhibition of total motility with significant reduction (P<0.05) at the maximum concentration of 200 μΜ when compared with the control. The concentrations of drugs that reduced total sperm motility to 50% of control (half maximal inhibitory concentration) were 2.76, 14.16 and 20.29 μΜ for phenytoin, lamotrigine and carbamazepine, respectively; and 2.53, 5.32 and 0.37 μΜ for amiodarone, procainamide and disopyramide, respectively. The anti-motility effects were reversible to various degrees. There was statistically insignificant difference in the inhibition of sperm viability among amiodarone, procainamide and disopyramide. Phenytoin demonstrated the most potent spermicidal action.Conclusions: VGSCs blockers have significant adverse effects on in-vitro motility of human spermatozoa. So in-vivo studies are required to determine their potential toxicological effects on human semen quality, which is an important factor regarding fertility. Moreover, these drugs have the potential to be developed into contact spermicidal