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Save imaging techniques like MRI and PET scanning are of great advantage here and these techniques also play an important role in refining animal experiments.20 Nevertheless, it is extremely difficult to eliminate all animal models from physiological research. Recent 3D tissue models of human colonic epithelium have been developed which will improve the mechanistic understanding of human intestinal function.11 The possibility of obtaining the information required through ethical research on human subjects or human tissue should be considered. Factors that confound the prediction of renal medullary oxygenation and risk of acute kidney injury from measurement of bladder urine oxygen tension. In recent years, most of the manuscripts published as a regular paper in ACTA Physiologica are based on animal experiments. [Extracted from the article]

The present paper deals with a fundamental issue in neuroscience: the inter-neuronal communication. The paper gives a brief account of our previous and more recent theoretical contributions to the subject and also reports new recent data that support some aspects of our proposal on two major modes of communication in the central nervous system: the wiring and the volume transmission. There exist two competing theories on inter-neuronal communication: the neuron doctrine and the theory of the diffuse nerve network, supported by Cajal and Golgi, respectively (see their respective Nobel Lectures). The present paper gives a brief account of a view on inter-neuronal communication in the brain, the volume and wiring transmission concept that to a great extent reconcile these two theories. Thus, the theory of volume and wiring transmission are summarized and its recent developments that allow to extend these two modes of communication from the cellular network to the molecular network level is also briefly illustrated. The explanatory value of this broadened view is further enhanced by our recent proposal on the existence of a Global Molecular Network enmeshing the entire central nervous system. It may be interesting to note that also the Global Molecular Network theory is reminiscent of the old reticular theory of Apathy. Finally, the so-called ‘tide hypothesis’ for diffusion of signals in the brain is briefly discussed and its possible extension to the molecular level is for the first time introduced. Early indirect evidence supporting volume transmission in the brain was the discovery of transmitter-receptor mismatches. Thus, as an experimental part of the present paper a new approach to evaluate transmitter-receptor mismatches is given and evidence for inter-relationships between temperature micro-gradients and mismatches is provided. [ABSTRACT FROM AUTHOR]

The article provides instructions for authors who want to submit their manuscripts to "Acta Physiologica," the official journal of the Federation of European Physiological Societies. The journal contains original contributions to physiology and related sciences such as pharmacology and biochemistry. It provides instructions for electronic submission.

Physiologically, macro- and microcirculation differ markedly as macrocirculation deals with pulsatile pressure and flow and microcirculation with steady pressure and flow. Various such haemodynamic aspects correspond to a large heterogeneity in the structure and function of the vascular tree. In the past, diseases such as hypertension and diabetes mellitus were classified on the basis of the structure and function of small and large arteries. The purpose of this paper is to review the cross-talk between the micro- and macrocirculation. We shall discuss this cross-talk from the perspective of the development, physiology and pathology of the entire arterial tree. [ABSTRACT FROM AUTHOR]

Exactly 50 years ago, I was a post‐doc in the laboratory of Olov Lindberg in Stockholm measuring fatty acid oxidation by mitochondria isolated from thermogenic brown adipose tissue, when we noticed a curious nonlinearity in the respiration rate. This initiated a convoluted chain of experiments revealing that the mitochondria were textbook demonstrations of the then novel and highly controversial "chemiosmotic hypothesis" of Peter Mitchell and that thermogenesis was regulated by a proton short‐circuit, mediated by a 32 kDa "uncoupling protein," UCP1, activated by fatty acid. This review is a personal account of the research into the bioenergetics of isolated brown adipocytes and isolated mitochondria, which led, after fifteen years of investigation, to what is still accepted as the "canonical" UCP1‐mediated mechanism of nonshivering thermogenesis, uniting whole animal physiology with mitochondrial bioenergetics. [ABSTRACT FROM AUTHOR]

Aims: Diets containing high‐fat and high sugar (HFHS) lead to overweight/obesity. Overweight/obesity increases the risk of infertility, and of the pregnant mother and her child for developing metabolic conditions. Overweight/obesity has been recreated in mice, but most studies focus on the effects of chronic, long‐term HFHS diet exposure. Here, we exposed mice to HFHS from 3 weeks prior to pregnancy with the aim of determining impacts on fertility, and gestational and neonatal outcomes. Methods: Time‐domain NMR scanning was used to assess adiposity, glucose, and insulin tolerance tests were employed to examine metabolic physiology, and morphological and proteomic analyses conducted to assess structure and nutrient levels of maternal organs and placenta. Results: Fertility measures of HFHS dams were largely the same as controls. HFHS dams had increased adiposity pre‐pregnancy, however, exhibited exacerbated lipolysis/hyper‐mobilization of adipose stores in late pregnancy. While there were no differences in glucose or insulin tolerance, HFHS dams were hyperglycemic and hyperinsulinemic in pregnancy. HFHS dams had fatty livers and altered pancreatic islet morphology. Although fetuses were hyperglycemic and hyperinsulinemic, there was no change in fetal growth in HFHS dams. There were also reductions in placenta formation. Moreover, there was increased offspring loss during lactation, which was related to aberrant mammary gland development and milk protein composition in HFHS dams. Conclusions: These findings are relevant given current dietary habits and the development of maternal and offspring alterations in the absence of an increase in maternal weight and adiposity during pregnancy, which are the current clinical markers to determine risk across gestation. [ABSTRACT FROM AUTHOR]

Protein kinase C and casein kinase substrate in neurons (PACSINs), or syndapins (synaptic dynamin‐associated proteins), are a family of proteins involved in the regulation of cell cytoskeleton, intracellular trafficking and signalling. Over the last twenty years, PACSINs have been mostly studied in the in vitro and ex vivo settings, and only in the last decade reports on their function in vivo have emerged. We first summarize the identification, structure and cellular functions of PACSINs, and then focus on the relevance of PACSINs in vivo. During development in various model organisms, PACSINs participate in diverse processes, such as neural crest cell development, gastrulation, laterality development and neuromuscular junction formation. In mouse, PACSIN2 regulates angiogenesis during retinal development and in human, PACSIN2 associates with monosomy and embryonic implantation. In adulthood, PACSIN1 has been extensively studied in the brain and shown to regulate neuromorphogenesis, receptor trafficking and synaptic plasticity. Several genetic studies suggest a role for PACSIN1 in the development of schizophrenia, which is also supported by the phenotype of mice depleted of PACSIN1. PACSIN2 plays an essential role in the maintenance of intestinal homeostasis and participates in kidney repair processes after injury. PACSIN3 is abundant in muscle tissue and necessary for caveolar biogenesis to create membrane reservoirs, thus controlling muscle function, and has been linked to certain genetic muscular disorders. The above examples illustrate the importance of PACSINs in diverse physiological or tissue repair processes in various organs, and associations to diseases when their functions are disturbed. [ABSTRACT FROM AUTHOR]

Recent advances in cardiac imaging have revitalized the assessment of fundamental physiological concepts. In the field of cardiac physiology, invasive measurements with pressure‐volume (PV) loops have served as the gold standard methodology for the characterization of left ventricular (LV) function. From PV loop data, fundamental aspects of LV chamber function are derived such as work, efficiency, stiffness and contractility. However, the parametrization of these aspects is limited because of the need for invasive procedures. Through the utilization of recent advances in echocardiography, magnetic resonance imaging and positron emission tomography, it has become increasingly feasible to quantify these fundamental aspects of LV function non‐invasively. Importantly, state‐of‐the‐art imaging technology enables direct assessment of myocardial performance, thereby extending functional assessment from the net function of the LV chamber, as is done with PV loops, to the myocardium itself. With a strong coupling to underlying myocardial physiology, imaging measurements of myocardial work, efficiency, stiffness and contractility could represent the next generation of functional parameters. The purpose of this review is to discuss how the new imaging parameters of myocardial work, efficiency, stiffness and contractility can bring cardiac physiologists, researchers and clinicians alike one step closer to underlying myocardial physiology. [ABSTRACT FROM AUTHOR]

The article discusses the reports within the issue, which were presented at the fifth international symposium on cell volume regulation and its physiological and pathophysiological implications, held in September 2005 in Copenhagen, Denmark. Major themes of the articles include sensors and transducers of the cell volume signal, effectors in cell volume regulations and the relation between cellular and extracellular volume and signal transduction in the brain.

Aim: To study brain‐sparing physiological responses in a rodent model of birth asphyxia which reproduces the asphyxia‐defining systemic hypoxia and hypercapnia. Methods: Steady or intermittent asphyxia was induced for 15‐45 minutes in anaesthetized 6‐ and 11‐days old rats and neonatal guinea pigs using gases containing 5% or 9% O2 plus 20% CO2 (in N2). Hypoxia and hypercapnia were induced with low O2 and high CO2 respectively. Oxygen partial pressure (PO2) and pH were measured with microsensors within the brain and subcutaneous ("body") tissue. Blood lactate was measured after asphyxia. Results: Brain and body PO2 fell to apparent zero with little recovery during 5% O2 asphyxia and 5% or 9% O2 hypoxia, and increased more than twofold during 20% CO2 hypercapnia. Unlike body PO2, brain PO2 recovered rapidly to control after a transient fall (rat), or was slightly higher than control (guinea pig) during 9% O2 asphyxia. Asphyxia (5% O2) induced a respiratory acidosis paralleled by a progressive metabolic (lact)acidosis that was much smaller within than outside the brain. Hypoxia (5% O2) produced a brain‐confined alkalosis. Hypercapnia outlasting asphyxia suppressed pH recovery and prolonged the post‐asphyxia PO2 overshoot. All pH changes were accompanied by consistent shifts in the blood‐brain barrier potential. Conclusion: Regardless of brain maturation stage, hypercapnia can restore brain PO2 and protect the brain against metabolic acidosis despite compromised oxygen availability during asphyxia. This effect extends to the recovery phase if normocapnia is restored slowly, and it is absent during hypoxia, demonstrating that exposure to hypoxia does not mimic asphyxia. [ABSTRACT FROM AUTHOR]

Aim Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles. Methods Global cerebral ischaemia was induced in male Wistar rats by bilateral common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral blood flow was determined by quantitative autoradiography. Intraparenchymal arterioles were isolated and pressurized, and concentration-response curves to endothelin-1 with and without the endothelin B receptor-selective antagonist BQ788 was generated. Endothelin B receptor expression was investigated by quantitative flow cytometry and immunohistochemistry. Results We observed increased endothelin-1-mediated contractility of parenchymal arterioles correlating with reduced cerebral blood flow of the cortex, hippocampus and caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin-1-mediated contractility was abolished by BQ788, and the vascular smooth muscle cell-specific expression of endothelin B receptors was significantly increased after global cerebral ischaemia. Conclusion Increased endothelin-1-mediated contractility and expression of endothelin B receptors in the intraparenchymal vasculature contributes to the development of delayed cerebral hypoperfusion after global cerebral ischaemia in combination with vascular changes of the pial vasculature. [ABSTRACT FROM AUTHOR]

Haemodynamic forces influence the functional properties of vascular endothelium. Endothelial cells (ECs) have a variety of receptors, which sense flow and transmit mechanical signals through mechanosensitive signalling pathways to recipient molecules that lead to phenotypic and functional changes. Arterial architecture varies greatly exhibiting bifurcations, branch points and curved regions, which are exposed to various flow patterns. Clinical studies showed that atherosclerotic plaques develop preferentially at arterial branches and curvatures, that is in the regions exposed to disturbed flow and shear stress. In the atheroprone regions, the endothelium has a proinflammatory phenotype associated with low nitric oxide production, reduced barrier function and increased proadhesive, procoagulant and proproliferative properties. Atheroresistant regions are exposed to laminar flow and high shear stress that induce prosurvival antioxidant signals and maintain the quiescent phenotype in ECs. Indeed, various flow patterns contribute to phenotypic and functional heterogeneity of arterial endothelium whose response to proatherogenic stimuli is differentiated. This may explain the preferential development of endothelial dysfunction in arterial sites with disturbed flow. [ABSTRACT FROM AUTHOR]

Micro RNAs (mi RNAs) have within the past decade emerged as key regulators of metabolic homoeostasis. Major tissues in intermediary metabolism important during development of the metabolic syndrome, such as β-cells, liver, skeletal and heart muscle as well as adipose tissue, have all been shown to be affected by mi RNAs. In the pancreatic β-cell, a number of mi RNAs are important in maintaining the balance between differentiation and proliferation (miR-200 and miR-29 families) and insulin exocytosis in the differentiated state is controlled by miR-7, miR-375 and miR-335. MiR-33a and MiR-33b play crucial roles in cholesterol and lipid metabolism, whereas miR-103 and miR-107 regulates hepatic insulin sensitivity. In muscle tissue, a defined number of mi RNAs (miR-1, miR-133, miR-206) control myofibre type switch and induce myogenic differentiation programmes. Similarly, in adipose tissue, a defined number of mi RNAs control white to brown adipocyte conversion or differentiation (miR-365, miR-133, miR-455). The discovery of circulating mi RNAs in exosomes emphasizes their importance as both endocrine signalling molecules and potentially disease markers. Their dysregulation in metabolic diseases, such as obesity, type 2 diabetes and atherosclerosis stresses their potential as therapeutic targets. This review emphasizes current ideas and controversies within mi RNA research in metabolism. [ABSTRACT FROM AUTHOR]

The article focuses on the studies to be presented at the Turkish Society of Physiological Sciences 42nd National Physiology Congress. The studies include "The Effect of Apelin on the Expression of Atrial Natriuretic Peptide in Cardiac Tissue," "Effect of Nicotine on The Smooth Muscle Cell Proliferation and Intracellular Calcium Levels," and "Lithium's Effect on Streptozotocin-induced Experimental Diabetes Rats of Vascular Smooth Muscle Cell Proliferation."

The article presents abstracts on physiology topics which include cardioventricular remodeling in teaching curricula, teaching physiology to medical students, and neuromodulation in neuropsychiatric diseases.

The article presents abstracts on physiology which include effect of azacytidine on prostate cancer cells, oxidative stress in prostate cancer patients and anti-oxidant activity of nebivolol in acute pancreatitis.

The article discusses the diagnosis, prognosis and treatment of channelopathies or ion channel diseases. Topics addressed include the role of ion channels in gate ion flux, the discovery and description of ion channel structure and functions, and the physiology and pathology of channel. The general classes of ion chanelopathies are cation channels, sodium channels, potassium channels, calcium channels, chloride channels, water channels and gap junction proteins.

Aim Drinking water induces short-term cardiovascular and metabolic changes. These effects are considered to be triggered by gastric distension and osmotic factors, but little is known about the influence of water temperature. Methods We determined, in a randomized crossover study, the acute cardiovascular and metabolic responses to 500 mL of tap water at 3 °C (cold), 22 °C (room) and 37 °C (body) in 12 young humans to ascertain an effect of water temperature. We measured continuous beat-to-beat haemodynamics, skin blood flux with laser-Doppler flowmetry and resting energy expenditure by indirect calorimetry starting with a 30-min baseline followed by a 4-min drink period and a subsequent 90-min post-drink observation. Results Ingestion of cold- and room-tempered water led to decreased heart rate ( P < 0.01) and double product ( P < 0.01), and increased stroke volume ( P < 0.05); these effects were not observed with body-tempered water. Drinking cold- and room-, but not body-tempered water, led to increased high frequency power of heart rate variability ( P < 0.05) and baroreflex sensitivity ( P < 0.05). Cold- and room-tempered water increased energy expenditure over 90 min by 2.9% ( P < 0.05) and 2.3% (ns), respectively, accompanied by a diminished skin blood flux ( P < 0.01), thereby suggesting that both small increases in heat production together with decreased heat loss contribute to warming up the ingested water to intra-abdominal temperature levels. Conclusions Overall, ingestion of cold- and room-, but not body-tempered water reduced the workload to the heart through a reduction in heart rate and double product which could be mediated by an augmented cardiac vagal tone. [ABSTRACT FROM AUTHOR]

Aims The adiposity rebound is the age in childhood when body mass index is at a minimum before increasing again. The age at rebound is highly variable. An early age is associated with increased obesity in later childhood and adult life. We have reported that an early rebound is predicted by low weight gain between birth and 1 year of age and resulting low body mass index at 1 year. Here, we examine whether age at adiposity rebound is determined by influences during infancy or is a consequence of foetal growth. Our hypothesis was that measurements of body size at birth are related to age at adiposity rebound. Methods Longitudinal study of 2877 children born in Helsinki, Finland, during 1934-1944. Results Early age at adiposity rebound was associated with small head circumference and biparietal diameter at birth, but not with other measurements of body size at birth. The mean age at adiposity rebound rose from 5.8 years in babies with a head circumference of ≤33 cm to 6.2 in babies with a head circumference of >36 cm ( P for trend = 0.007). The association between thinness in infancy and early rebound became apparent at 6 months of age. It was not associated with adverse living conditions. In a simultaneous regression, small head circumference at birth, high mother's body mass index and tall maternal stature each had statistically significant trends with early adiposity rebound ( P = 0.002, <0.001, 0.004). Conclusion We hypothesize that the small head size at birth that preceded an early adiposity rebound was the result of inability to sustain a rapid intra-uterine growth trajectory initiated in association with large maternal body size. This was followed by catch-up growth in infancy, and we hypothesize that this depleted the infant's fat stores. [ABSTRACT FROM AUTHOR]

Aim: Sprint exercise is characterized by repeated sessions of brief intermittent exercise at a high relative workload. However, little is known about the effect on mTOR pathway, an important link in the regulation of muscle protein synthesis. An earlier training study showed a greater increase in muscle fibre cross-sectional area in women than men. Therefore, we tested the hypothesis that the activation of mTOR signalling is more pronounced in women than in men. Healthy men ( n = 9) and women ( n = 8) performed three bouts of 30-s sprint exercise with 20-min rest in between. Methods: Multiple blood samples were collected over time, and muscle biopsy specimens were obtained at rest and 140 min after the last sprint. Results: Serum insulin increased by sprint exercise and more so in women than in men [gender (g) × time (t)]: P = 0.04. In skeletal muscle, phosphorylation of Akt increased by 50% (t, P = 0.001) and mTOR by 120% (t, P = 0.002) independent of gender. The elevation in p70S6k phosphorylation was larger in women (g × t, P = 0.03) and averaged 230% ( P = 0.006) as compared to 60% in men ( P = 0.04). Phosphorylation rpS6 increased by 660% over time independent of gender (t, P = 0.003). Increase in the phosphorylation of p70S6k was directly related to increase in serum insulin ( r = 0.68, P = 0.004). Conclusion: It is concluded that repeated 30-s all-out bouts of sprint exercise separated by 20 min of rest increases Akt/ mTOR signalling in skeletal muscle. Secondly, signalling downstream of mTOR was stronger in women than in men after sprint exercise indicated by the increased phosphorylation of p70S6k. [ABSTRACT FROM AUTHOR]

Aim: The effects of obesity on cardiac function during incremental exercise to peak oxygen consumption ( VO2peak) have not been previously described. The purpose of this study was to compare submaximal and maximal cardiac function during exercise in normal-weight and obese adults. Methods: Normal-weight ( n = 20; means ± SE: age = 21.9 ± 0.5 years; BMI = 21.8 ± 0.4 kg m−2) and obese ( n = 15; means ± SE: age = 25.1 ± 5.2 years; BMI = 34.1 ± 01.0 kg m−2) participants were assessed for body composition, VO2peak and cardiac variables (thoracic bioimpedance analysis) at rest and at heart rates (HR) of 110, 130, 150 and 170 beats min−1 and maximal HR during incremental cycling exercise to exhaustion. Differences between groups were assessed with mixed-model ancova with repeated measures. Cardiac variables were statistically indexed for body surface area and resting HR. VO2 and arteriovenous oxygen difference (a- vO2) were statistically indexed for fat-free mass and resting HR. Results: Significant main effects for group indicated obese participants had higher cardiac output (Q) index and stroke volume (SV) index but lower ejection fraction (EF) and a- vO2 index during incremental exercise to exhaustion compared with their normal-weight peers, despite similar submaximal and maximal VO2 and absolute power outputs ( P < 0.05). Conclusions: Our findings suggest that although Q index and SV index were higher in obese, young adults, EF and a- vO2 index were significantly lower when compared to matched, normal-weight adults. [ABSTRACT FROM AUTHOR]

Aim: Endurance and resistance training (ET and RT, respectively) in older subjects have been proven beneficial against metabolic or cardiovascular disorders and against sarcopaenia respectively. Like ET, RT may also increase muscle oxidative capacities. In addition, it could be questioned whether RT, similarly to ET, is able to increase muscle energetic stores such as intra-myocellular lipids (IMCL) and glycogen contents. To evaluate a possible ET- and RT-induced parallel increase in oxidative capacity and energetic stores, active elderly men (72 ± 2 years) were submitted to a 14-week training programme (three times week−1) combining lower body endurance and upper body resistance. Methods: Muscle samples were collected in ET vastus lateralis (VLat) and RT deltoid (Del) muscles before and after training. IMCL and glycogen contents were assessed by histochemistry (Oil Red O and periodic acid-Schiff staining, respectively) and by biochemical assay for glycogen. Citrate synthase (CS, marker of mitochondrial citric acid cycle), β-hydroxyacyl coenzyme A dehydrogenase (β-HAD, beta-oxidation) and phosphofructokinase (PFK, glycolytic pathway) activities were determined and so was the capillary interface index (LC/PF). Results: Both training regimens significantly increased CS and LC/PF in ET-VLat and RT-Del. IMCL content and β-HAD activity increased ( P < 0.05) only in ET-VLat, whereas PFK activity increased ( P < 0.05) only in RT-Del. Glycogen content was not significantly altered in response to training in both muscles. Conclusion: Unlike RT, which induced an increase in PFK, ET is able to increase IMCL content and β-oxidation capacity in active elderly men, even though both training may improve CS activity and LC/PF. [ABSTRACT FROM AUTHOR]

The authors reflect on good publication practices in physiology. They stress the significance of author's awareness in the manuscript's content to monitor and check its completeness. Moreover, they notes the essential role of identifying fraud and auto-plagiarism in the manuscript and explore measures in taking research involving human and animals.

The article discusses the thesis about the regulation and physiological function of Nav1.5 and KCNQ1 channels. It states that tight regulation of the ionic currents is necessary to maintain many physiological functions within the body. It notes that the cardiac sodium current is responsible for the progression and initiation of the action potential, while current conducted by KCNQ1/KCNE1 channels resembles the cardiac I[K,s]current, which is important for repolarization.

This study investigated the effect of a 15-week life style intervention (hypocaloric diet and regular exercise) on glucose tolerance, skeletal muscle lipids and muscle metabolic adaptations in 14 female and 9 male morbidly obese subjects (age: 32.5 ± 2.3 years, body mass index: 46.1 ± 1.9 kg m). Before and after the life style intervention, an oral glucose tolerance test was performed and a muscle biopsy was obtained in the fasted state. Maximal oxygen uptake was measured by an indirect test. After the intervention, body weight was decreased ( P < 0.05) by 11 ± 1%, maximal oxygen uptake increased ( P < 0.05) by 18 ± 5% and glucose tolerance increased ( P < 0.05) by 12 ± 3%. Muscle glycogen was significantly increased by 47 ± 14%, but muscle ceramide and triacylglycerol content remained completely unchanged. No sex difference was observed for any of these parameters, but during submaximal exercise a marked decrease ( P < 0.05) of 15 ± 2% in respiratory exchange ratio was seen only in females indicating an enhanced fat oxidation. Despite a marked weight loss and an improved aerobic capacity muscle ceramide and triacylglycerol remained unchanged after intensive life style intervention, and muscle lipids hence do not seem to play a major role for the improved glucose tolerance in these morbidly obese subjects. Interestingly, only the females improved fat oxidation during submaximal exercise after the intervention implying the presence of a sex-dependent response to intensive life style adaptation. [ABSTRACT FROM AUTHOR]

The gastrointestinal (GI) tract is fundamental for the intake of fluid and electrolytes and accommodates a large proportion of bodily hemodynamics and host defence systems. Despite that the renin-angiotensin system (RAS) is a prominent regulatory system for fluid and electrolyte homeostasis its impact on GI physiology is only little explored. Recent data indicate that RAS is well expressed and active in the GI tract although exact physiological roles are to be settled. There are several reports showing influences by RAS and its key mediator angiotensin II (AngII) on intestinal epithelial fluid and electrolyte transport and data are accumulating, suggesting involvement in GI mucosal inflammation and carcinogenesis. Of particular interest is the increasing amount of experimental support for the involvement of AngII formation and actions via the AngII subtype 1 (AT1) receptor in the pathogenesis and treatment of inflammatory bowel disease. The picture of RAS in the GI tract is, however, far from complete. Because RAS is an important application area for reno-cardiovascular diseases, a number of pharmacological agents as well as research technologies already exist and can in the future be used for GI research. A marked expansion of knowledge concerning the role of RAS in GI physiology and pathophysiology is to be expected. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) and reactive nitrogen species have generally been considered as being highly reactive and cytotoxic molecules. Besides their noxious effects, ROS participate in physiological processes in a carefully regulated manner. By way of example, microbicidal ROS are produced in professional phagocytes, ROS function as short-lived messengers having a role in signal transduction and, among other processes, participate in the synthesis of the iodothyronine hormones, reproduction, apoptosis and necrosis. Because of their ability to mediate a crosstalk between key molecules, their role might be dual (at least in some cases). The levels of ROS increase from a certain age, being associated with various diseases typical of senescence. The aim of this review is to summarize the recent findings on the physiological role of ROS. Other issues addressed are an increase in ROS levels during ageing, and the possibility of the physiological nature of this process. [ABSTRACT FROM AUTHOR]

Hypoxia is a consequence of inadequate oxygen availability. At the cellular level, lowered oxygen concentration activates signal cascades including numerous receptors, ion channels, second messengers, as well as several protein kinases and phosphatases. This, in turn, activates trans-factors like transcription factors, RNA-binding proteins and miRNAs, mediating an alteration in gene expression control. Each cell type has its unique constellation of oxygen sensors, couplers and effectors that determine the activation and predominance of several independent hypoxia-sensitive pathways. Hence, altered gene expression patterns in hypoxia result from a complex regulatory network with multiple divergences and convergences. Although hundreds of genes are activated by transcriptional control in hypoxia, metabolic rate depression, as a consequence of reduced ATP level, causes inhibition of mRNA translation. In a multi-phase response to hypoxia, global protein synthesis is suppressed, mainly by phosphorylation of eIF2-alpha by PERK and inhibition of mTOR, causing suppression of 5′-cap-dependent mRNA translation. Growing evidence suggests that mRNAs undergo sorting at stress granules, which determines the fate of mRNA as to whether being translated, stored, or degraded. Data indicate that translation is suppressed only at ‘free’ polysomes, but is active at subsets of membrane-bound ribosomes. The recruitment of specific mRNAs into subcellular compartments seems to be crucial for local mRNA translation in prolonged hypoxia. Furthermore, ribosomes themselves may play a significant role in targeting mRNAs for translation. This review summarizes the multiple facets of the cellular adaptation to hypoxia observed in mammals. [ABSTRACT FROM AUTHOR]

The article presents a dissertation of studies of the organization of the human nociceptive withdrawal reflex. It focuses on sensory convergence and stimulation site dependency. A list of abbreviations, including BF for biceps femoris and IL for iliopsoas, that are used are also listed. Two aspects of reflex physiology namely the organization of the reflex and the sensory integration/convergence at the spinal level were investigated in the studies.

Aim: To clarify the time-related changes in cardiac function and the mechanism underlying the cardiac dysfunction present in diabetes mellitus, we studied mechanical responses induced by α1- and β-adrenoceptors, the Ca2+-entry promoter Bay K 8644- and ryanodine (an agent known to inhibit Ca2+ release from the sarcoplasmic reticulum) in papillary muscles from streptozotocin (STZ)-induced diabetic and age-matched control rats. Methods: Male Wistar rats received a single injection of STZ (60 mg kg−1) via the tail vein to induce diabetes. For the mechanical studies, papillary muscle preparations were suspended in an organ bath and isometric contractions were measured in 1-, 4-, and 10-week STZ-induced diabetic and age-matched control rats. Results: In 1-week diabetic rats, the contractions induced by isoproterenol, methoxamine and Bay K 8644 were unchanged (vs. age-matched controls). In 4-week diabetic rats, (a) the isoproterenol- and Bay K 8644-induced contractions were impaired, (b) sensitivity to ryanodine was reduced, whereas (c) the methoxamine-induced contraction was unchanged. In 10-week diabetic rats, the isoproterenol- and Bay K 8644-induced contractile responses were impaired and the sensitivity to ryanodine was reduced, but in sharp contrast the methoxamine-induced contraction was enhanced. Both the mRNA level for the α1A adrenoceptor (but not the α1B or α1D mRNAs) and α1A adrenoceptor protein were increased in 10-week diabetic rats (vs. age-matched controls). Conclusion: These results suggest that impairments of β-adrenergic and Ca2+-handling mechanisms occur early in the development of cardiomyopathy in STZ-induced diabetic rats, and that this is followed by augmentation of α1A adrenoceptor-mediated inotropy due to α1A adrenoceptor upregulation. [ABSTRACT FROM AUTHOR]

Apoptosis is an active process with distinct features including loss of cell volume, chromatin condensation, internucleosomal DNA fragmentation, and apoptotic body formation. Among the classical characteristics that define apoptosis, the loss of cell volume has become a very important component of the programmed cell death process. Changes in cell volume result from alterations in the homeostasis of ions and in particular the movement of Na+ and K+ ions. Most living cells have a high concentration of intracellular K+ and a low concentration of intracellular Na+. This is in contrast to the outside of the cell, where there is a high concentration of extracellular Na+ and a low concentration of extracellular K+. Thus a concentration gradient exists for the loss and gain of intracellular K+ and Na+, respectively. This gradient is maintained through the activity of various ionic channels and transporters, but predominantly the activity of the Na+/K+-ATPase. During apoptosis, there is compelling evidence indicating an early increase in intracellular Na+ followed by a decrease in both intracellular K+ and Na+ suggesting a regulatory role for these cations during both the initial signalling, and the execution phase of apoptosis. Recent studies have shown that the Na+/K+-ATPase is involved in controlling perturbations of Na+ and K+ homeostasis during apoptosis, and that anti-apoptotic Bcl-2 and Bcl-XL molecules influence these ionic fluxes. Finally, understanding the regulation or deregulation of ionic homeostasis during apoptosis is critical to facilitate the treatment of cardiovascular, neurological, and renal diseases where apoptosis is known to play a major role. [ABSTRACT FROM AUTHOR]

Aim: By mathematical modelling, we analyse conditions for near-isotonic and isotonic transport by mammalian kidney proximal tubule. Methods: The model comprises compliant lateral intercellular space ( lis) and cells, and infinitely large luminal and peritubular compartments with diffusible species: Na+, K+, Cl− and an intracellular non-diffusible anion. Unknown model variables are solute concentrations, electrical potentials, volumes and hydrostatic pressures in cell and lis, and transepithelial potential. We used data mainly from rat proximal tubule to model epithelial cells and interspace with luminal and peritubular baths of identical composition. Results: The model of the tubular epithelium with physiological water permeability and paracellular electrical resistance generates solute coupled water uptake with an approx. 3% hypertonic absorbate. This function remains unperturbed following ‘blocking’ of apical water channels and in ‘aquaporin-null’ simulation. Reduced rate of volume reabsorption in AQP(-/-) mice would also require decreased apical sodium permeability. Paracellular convection accounts for approx. 36% of the net Na+ absorption, and the model epithelium accomplishes uphill water transport similar to rat proximal tubule. Na+ recirculation is required for truly isotonic transport. The tonicity of the absorbate and the recirculation flux depend critically on ion permeabilities of interspace basement membrane. Conclusion: Our model based on solute-solvent coupling in lateral space simulates major physiological features of proximal tubule, including significantly lower water permeability of the AQP1-null preparation, and a ratio of net sodium uptake and oxygen consumption exceeding that predicted from stoichiometry of the Na+/K+-pump. Physical properties of interspace basement membrane are critical for obtaining near-isotonic and truly isotonic transport. [ABSTRACT FROM AUTHOR]

The article presents abstracts on physiology which include migraine, calcium in heart and physiology of sport sciences and exercises.

An introduction is presented in which the editor discusses various topics within the issue including role of nitric oxide in the modulation of central angiotensin receptor, role of angiotensin receptor system in baroreflex, and nitric oxide synthase activity within the nucleus tractus solitarius.

In the vertebrate brain, neural stem cells (NSCs) generate both neuronal and glial cells throughout life. However, their neuro‐ and gliogenic capacity changes as a function of the developmental context. Despite the growing body of evidence on the variety of intrinsic and extrinsic factors regulating NSC physiology, their precise cellular and molecular actions are not fully determined. Our review focuses on thyroid hormone (TH), a vital component for both development and adult brain function that regulates NSC biology at all stages. First, we review comparative data to analyse how TH modulates neuro‐ and gliogenesis during vertebrate brain development. Second, as the mammalian brain is the most studied, we highlight the molecular mechanisms underlying TH action in this context. Lastly, we explore how the interplay between TH signalling and cell metabolism governs both neurodevelopmental and adult neurogenesis. We conclude that, together, TH and cellular metabolism regulate optimal brain formation, maturation and function from early foetal life to adult in vertebrate species. [ABSTRACT FROM AUTHOR]

EPO expressing cells according to additional cell MV3 cells were compared to the corresponding mock-transfected control cells. Tissue-resident immune cells play key roles in organ physiology by their cross-talk with non-immune cells and providing Methods mCCDcl1 cells derived from principal cells of a microdissected murine CCD were cultured on permeable support to Myotoxicity in mice, cytotoxicity on C2C12 cells) have been studied in the past, detailed effects on adult cells on a molecular. [Extracted from the article]

Single -cell genomics methods have greatly improved our ability to study minor cell populations in complex mixtures of cells We can now routinely profile many thousands of cells by single-cell RNA-seq Cell Interaction by Multiplet sequencing (CIM-seq) is based on sequencing of cell multiplets from incompletely dissociated In cells in general and in neurons in particular and their activity is crucial for keeping normal cell Effector/memory (TEM) cells limits cell proliferation and tumor suppression. [Extracted from the article]