Current research in physiology最新文献

Lead acetate associated tissue injury has been linked to altered antioxidant defenses, hyperuricemia and inflammation. We hypothesized that watermelon rind extract, would ameliorate lead acetate-induced hepato-renal injury.

Thirty Male Wistar rats received distilled water, lead acetate (Pb; 5 mg/kg) with or without watermelon rind extract (WM; 400 mg/kg; WM + Pb; 15 days of WM pretreatment); Pb + WM (15 days of WM post treatment) and simultaneous treatment (WM-Pb) for 30 days.

Lead toxicity led to elevated serum malondialdehyde, creatinine, urea, uric acid, lactate dehydrogenase, liver injury enzymes, as well as decreased body weight. Decreased serum levels of reduced glutathione, nitric oxide, total protein and glutathione peroxidase activity was also observed. However, these alterations were ameliorated by watermelon rind extract in lead acetate-treated rats.

Watermelon rind ethanol extract protects against lead acetate-induced hepato-renal injury through improved antioxidant defenses at least in part, via uric acid/nitric oxide-dependent pathway signifying the health benefits of this agricultural waste and a potential for waste recycling while limiting environmental pollution.

Maternal treatment with dexamethasone induces oxidative stress in the reproductive structures of offspring. Consumption of Allium cepa Linn improves antioxidant status. This study was designed to evaluate the protective role of Allium cepa Linn juice on maternal dexamethasone induced alterations in reproductive functions of the female offspring of Wistar rats.

Twenty lactating dams (180–200 ​g) were randomly assigned into four groups (n ​= ​5) on the day of parturition and treated as follows during lactation for 21 days: Control (5 ​ml/kg BW distilled water); Dexamethasone (60 ​μg/kg BW); Allium cepa (5 ​ml/kg BW); Dexamethasone ​+ ​Allium cepa (60 ​μg/kg BW ​+ ​5 ​ml/kg BW). The female offspring were separated at birth. Days of vaginal opening and first oestrus cycle, length and frequency of estrous cycle as well as serum hormonal profiles were assessed as measure of reproductive functions. Ovarian superoxide dismutase (SOD) activity, catalase activity and malondialdehyde (MDA) level were measured as indices of oxidative stress.

Oestrous cycle length, frequencies of diestrus as well as the Ovarian MDA were significantly increased (p ​< ​0.05) in dexamethasone (DEX) group relative to control group. Serum 17β-oestradiol and corticosterone level in addition to SOD and catalase activities were significantly reduced (p ​< ​0.05) in DEX group relative to control. Co-administration of Dex with Allium cepa Linn juice reduced the oestrous length, frequency of diestrous as well as ovarian MDA. There was also a significant increase in serum 17β-oestradiol, ovarian SOD and catalase activity.

The results suggest that Allium cepa could protect against alterations in reproductive functions of offspring induced by maternal treatment with dexamethasone during lactation in Wistar rats. The flavonoid constituent of onion may also help in reducing oxidative stress in the offspring.

Objective

Sprint-interval training (SIT) and intermittent fasting are effective independent methods in achieving clinical health outcomes. However, the impact of both modalities when performed concurrently is unclear. The aim of this study was to compare the effects of 6 weeks of SIT performed in the fasted versus fed state on physiological and clinical health markers in healthy adults. Methods. Thirty recreationally-active participants were equally randomised into either the fasted (FAS; 4 males, 11 females) or the fed (FED; 6 males, 9 females) group. For all exercise sessions, FAS participants had to fast ≥10 h prior to exercising while FED participants had to consume food within 3 h to exercise. All participants underwent three sessions of SIT per week for 6 weeks. Each session consists of repeated bouts of 30-s Wingate Anaerobic cycle exercise. Pre- and post-training peak oxygen uptake (VO_2peak), isokinetic leg strength, insulin sensitivity, blood pressure and serum lipid levels were assessed. Results. There were no differences in baseline physiological and clinical measures between both groups (all p > 0.05). VO_2peak improved by 6.0 ± 8.8% in the FAS group and 5.3 ± 10.6% in the FED group (both p < 0.05), however the difference in improvement between groups was not statistically significant (p > 0.05). A similar pattern of results was seen for knee flexion maximum voluntary contraction at 300°·s⁻¹. SIT training in either fasted or fed state had no impact on insulin sensitivity (both p > 0.05). There was significant reduction in diastolic blood pressure (8.2 ± 4.2%) and mean arterial pressure (7.0 ± 3.2%) in the FAS group (both p < 0.05) but not FED group (both p > 0.05). Conclusion. VO_2peak and leg strength improved with SIT regardless of whether participants trained in the fasted or fed state. Chronic SIT in the fasted state may potentially reduce blood pressure to a greater extent than the same chronic SIT in the fed state.

Calorie restriction (CR) involves a reductions of calorie intake without altering the nutritional balance, and has many beneficial effects, such as improving oxidative metabolism and extending lifespan. However, CR decreases in skeletal muscle mass and fat mass in correlation with the reduction in food intake. Lactate is known to have potential as a signaling molecule rather than a metabolite during exercise. In this study, we examined the effects of the combination of caloric restriction and lactate administration on skeletal muscle adaptation in order to elucidate a novel role of lactate. We first demonstrated that daily lactate administration (equivalent to 1 g/kg of body weight) for 2 weeks suppressed CR-induced muscle atrophy by activating mammalian/mechanistic target of rapamycin (mTOR) signaling, a muscle protein synthesis pathway, and inhibited autophagy-induced muscle degradation. Next, we found that lactate administration under calorie restriction enhanced mitochondrial enzyme activity (citrate synthase and succinate dehydrogenase) and the expression of oxidative phosphorylation (OXPHOS) protein expression. Our results suggest that lactate administration under caloric restriction not only suppresses muscle atrophy but also improves mitochondrial function.

Zinc finger protein 1 (ZPR1) is required for cellular replication and viability. Recently, ZPR1 variant rs964184 has been repeatedly linked to high plasma triglyceride levels, metabolic syndrome, type 2 diabetes mellitus (T2DM), and nonalcoholic fatty liver disease (NAFLD), suggesting its involvement in lipid metabolism. This article attempts to explain how ZPR1 contributes to the mechanism of high-fat diet-associated cognitive decline through three premises: i) high-fat diet results in cognitive decline, ii) ZPR1 deficiency also results in cognitive decline, and iii) high-fat diet results in ZPR1 deficiency. Therefore, ZPR1 has the potential to be the connection between high-fat diet and cognitive decline. The two modalities of cognitive decline caused by low concentrations of ZPR1 are reduced brain-derived growth factor (BDNF) synthesis and neuron death, both occurring in the hippocampus. Downregulation of ZPR1 may lead to decreased synthesis of BDNF due to reduced concentrations of peroxisome proliferator-activated receptor-gamma (PPAR-γ), tropomyosin receptor kinase B (Trk B), and cAMP response element-binding protein (CREB), resulting in reduced ability to form and retain long-term memory as well as reduced neuroplasticity. Likewise, low concentrations of ZPR1 facilitate neuron death by producing lower amount of spinal motor neuron (SMN) protein, causing genomic instability, activating mixed-lineage protein kinase 3 (MLK3), mitogen-activated protein kinase 7 (MKK7), and c-Jun N-terminal kinase 3 (JNK3) signal cascade, and ultimately resulting in the activation of Caspase 3.

This study investigated the influence of heat pre-conditioning on the recovery of muscle torque, microvascular function, movement economy and stride mechanics following exercise-induced muscle damage (EIMD). Twenty male participants were equally assigned to a control (CON) and an experimental group (HEAT), and performed a 30-min downhill run (DHR) to elicit EIMD. HEAT group received three consecutive days of heat exposure (45.1 ​± ​3.2 ​min of hot water immersion at 42 ​°C) prior to DHR. Microvascular function (near-infrared spectroscopy), maximal voluntary contraction (MVC) torque of the knee extensors, as well as two treadmill-based steady-state runs performed below (SSR-1) and above (SSR-2) the first ventilatory threshold were assessed prior to DHR and repeated for four consecutive days post-DHR (D1-POST to D4-POST). The decline in MVC torque following EIMD was attenuated in HEAT compared with CON at D1-POST (p ​= ​0.037), D3-POST (p ​= ​0.002) and D4-POST (p ​= ​0.022). Muscle soreness increased in both CON and HEAT, but was significantly attenuated in HEAT compared with CON at D2-POST (p ​= ​0.024) and D3-POST (p ​= ​0.013). Microvascular function decreased in CON from D1-POST to D3-POST (p ​= ​0.009 to 0.018), and was lower compared with HEAT throughout D1-POST to D3-POST (p ​= ​0.003 to 0.017). Pre-heat treatment decreased the magnitude of strength loss and muscle soreness, as well as attenuated the decline in microvascular function following EIMD. Heat treatment appears a promising pre-conditioning strategy when embarking on intensified training periods or competition.

Progressive sodium retention and cumulative plasma volume expansion occur to support the developing fetus during pregnancy. Sodium retention is regulated by individual tubular transporters and channels. An increase or decrease in any single transporter could cause a change in sodium balance. Understanding the time-course for changes in each sodium transporter during pregnancy will enable us to understand progressive sodium retention seen in pregnancy. Here, we examined the activity of the major apical sodium transporters found in the nephron using natriuretic response tests in virgin, early pregnant, mid-pregnant, and late pregnant rats. We also measured renal and serum aldosterone levels. We found that furosemide sensitive sodium transport (NKCC2) is only increased during late pregnancy, thiazide sensitive sodium transport (NDCBE/pendrin) is increased in all stages of pregnancy, and that benzamil sensitive sodium transport (ENaC) is increased beginning in mid-pregnancy. We also found that serum aldosterone levels progressively increased throughout gestation and kidney tissue aldosterone levels increased only during late pregnancy. Here we have shown progressive turning on of specific sodium transport mechanisms to help support progressive sodium retention through the course of gestation. These mechanisms contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

Silent information Regulators (SIRT1) gene stimulates antioxidants’ expression, repairs cells damaged by oxidative stress (OS), and prevents the cells’ dysfunction. In particular, the role of different Sirtuins, particularly SIRT1 in reproduction, has been widely studied over the past decade. Decreased SIRT 1 causes mitochondrial dysfunction by increasing Reactive Oxygen Species (ROS), lipid peroxidation, and DNA damage in both male and female gametes (Sperms and Oocytes), leading to infertility. In the female reproductive system, SIRT1 regulates proliferation and apoptosis in granulosa cells (GCs), and its down-regulation is associated with a reduced ovarian reserve. SIRT1 also modulates the stress response to OS in GCs by targeting a transcription factor vital for ovarian functions and maintenance.

ROS-mediated damage to spermatozoa’s motility and morphology is responsible for 30–80% of men’s infertility cases. High levels of ROS can cause damage to deoxyribo nucleic acid (DNA) in the nucleus and mitochondria, lipid peroxidation, apoptosis, inactivation of enzymes, and oxidation of proteins in spermatozoa. SIRT 1 is a cardioprotective molecule that prevents atherosclerosis by modulating various mechanisms such as endothelial injury due to impaired nitric oxide (NO) production, inflammation, OS, and regulation of autophagy. SIRT 1 is abundantly expressed in tubular cells and podocytes. It is also found to be highly expressed in aquaporin 2 positive cells in the distal nephron suggesting its involvement in sodium and water handling. SIRT1 improves insulin resistance by reducing OS and regulating mitochondrial biogenesis and function. It also decreases adiposity and lipogenesis and increases fatty acid oxidation. So, its involvement in the multiple pathways ensures its unique role in reproductive and metabolic derangement mechanisms.

Background

Time-domain and non-linear methods can be used to quantify beat-to-beat repolarization variability but whether measures of repolarization variability can predict ventricular arrhythmogenesis in mice have never been explored.

Methods

Left ventricular monophasic action potentials (MAPs) were recorded during constant right ventricular 8 ​Hz pacing in Langendorff-perfused mouse hearts, in the presence or absence of the gap junction and sodium channel inhibitor heptanol (0.1, 0.5, 1 or 2 ​mM).

Results

Under control conditions, mean action potential duration (APD) was 39.4 ​± ​8.1 ​ms. Standard deviation (SD) of APDs was 0.3 ​± ​0.2 ​ms, coefficient of variation was 0.9 ​± ​0.8% and the root mean square (RMS) of successive differences in APDs was 0.15 ​± ​0.14 ​ms. Poincaré plots of APD_n+1 against APD_n revealed ellipsoid morphologies with a SD along the line-of-identity (SD2) to SD perpendicular to the line-of-identity (SD1) ratio of 4.6 ​± ​2.1. Approximate and sample entropy were 0.61 ​± ​0.12 and 0.76 ​± ​0.26, respectively. Detrended fluctuation analysis revealed short- and long-term fluctuation slopes of 1.49 ​± ​0.27 and 0.81 ​± ​0.36, respectively. Heptanol at 2 ​mM induced ventricular tachycardia in five out of six hearts. None of the above parameters were altered by heptanol during which reproducible electrical activity was observed (KW-ANOVA, P ​> ​0.05). Contrastingly, SD2/SD1 decreased to 2.03 ​± ​0.41, approximate and sample entropy increased to 0.82 ​± ​0.12 and 1.45 ​± ​0.34, and short-term fluctuation slope decreased to 0.82 ​± ​0.19 during the 20-s period preceding spontaneous ventricular tachy-arrhythmias (n ​= ​6, KW-ANOVA, P ​< ​0.05).

Conclusion

Measures of repolarization variability, such as SD2/SD1, entropy, and fluctuation slope are altered preceding the occurrence of ventricular arrhythmogenesis in mouse hearts. Changes in these variables may allow detection of impending arrhythmias for early intervention.

Postural orthostatic tachycardia syndrome (POTS) is a disorder epitomized by the story of the blind men and the elephant. Patients may see primary care internists or pediatricians due to fatigue, be referred to neurologists for “spells”, to cardiologists for evaluation of pre-syncope or chest pain, to gastroenterologists for nausea or dyspepsia, and even pulmonologists for dyspnea. Adoption of a more systematic approach to their evaluation and better characterization of patients has led to greater understanding of comorbidities, hypotheses prompting mechanistic investigations, and pharmacologic trials. Recent work has implicated disordered sympathetic nervous system activation in response to central (thoracic) hypovolemia. It is this pathway that leads one zero in on a putative focal point from which many of the clinical manifestations can be explained – specifically the carotid body. Despite heterogeneity in etiopathogenesis of a POTS phenotype, we propose that aberrant activation and response of the carotid body represents one potential common pathway in evolution. To understand this postulate, one must jettison isolationist or reductionist ideas of chemoreceptor and baroreceptor functions of the carotid body or sinus, respectively, and consider their interaction and interdependence both locally and centrally where some of its efferents merge. Doing so enables one to connect the dots and appreciate origins of diverse manifestations of POTS, including dyspnea for which the concept of neuro-mechanical uncoupling is wanting, thereby expanding our construct of this symptom. This perspective expounds our premise that POTS has a prominent respiratory component.