Clinical Physiology: Role in Studying Basic Problems of the Regulation of Renal Functions in Humans

Clinical physiology is described as a unique branch of human physiology that allows basic regulatory mechanisms of renal functions to be revealed. The analysis of physiological mechanisms that change the renal functions under the influence of endogenous or exogenous factors made it possible to detect new aspects of the regulatory system involved. The following problems are discussed: (1) the role of autacoids in the regulation of ion and water transport in the kidney; (2) the significance of functional loading tests for assessing the main components of the regulatory system of water and electrolyte balance; (3) the variety of sources of human blood hormones; and (4) the intranephron redistribution of water and electrolyte flows, which does not change their excretion by the kidney but affects the regulation of the totality of body functions.     

Human physiology: kidney

The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.     

Human physiology: The kidney

The content of human physiology as an independent part of modern physiology is discussed. It is substantiated that not only special sections of physiology where functions are specific for humans (the physiology of intellectual activity, speech, labor, and sport), but also the characteristics of functions and the specificity of regulation of each of the physiological systems are subjects of human physiology. The boundaries of the norm, the characteristics of regulation in humans, new chapters of renal physiology that appeared due to the achievements of molecular physiology and require fundamentally new approaches are exemplified by the physiology of the kidneys and water-electrolyte balance.     

The caudal neurosecretory system

Summary Recent information on the caudal neurosecretory system (urophysis) is collated, with special reference to cellular biology including neural relations, activity and chemistry of the biological principles associated with the urophysis, pharmacological analysis of the receptors for these principles, and their possible functions in a physiological sense. The existence of at least two principles, urotensins I and II, is well established. They differ pharmacologically and chemically and may arise from different cell types. At present, osmoregulation, cardiovascular regulation and reproduction are the most likely aspects of organismal physiology wherein these principles may be involved.Dedicated to Professor Doctor Berta Scharrer on the occasion of her seventieth birthday, with profound admiration and affection     

Uncoupling proteins in modulation of mitochondrial functions--therapeutic prospects

Enormous interest in mitochondrial uncoupling proteins (UCPs) is caused by relevant impact of these energy-dissipating systems on cellular energy transduction. A key role of UCPs in regulation of mitochondrial metabolism is supported by existence of their different isoforms in various mammalian tissues. Recent studies have shown that UCPs have an important part in pathogenesis of various disorders, such as obesity, type-2 diabetes, cachexia, aging or tumor. The obscure roles of UCPs in normal physiology and their emerging role in pathophysiology, provide exciting potential for further investigation. However, neither the exact physiological nor biochemical roles of UCP homologues are well understood. Therefore, providing mechanistic explanation of their functions in cellular physiology may be the basis for potential farmacological targeting of UCPs in future on clinical scale.     

Calcitonin, an enigmatic hormone: does it have a function?

This editorial presents our view of the status of thyroidal calcitonin (TCT) in mammalian physiology. The discovery of calcitonin (CT) enabled the development of a valuable therapeutic agent but the early experiments most likely misled us with regard to its physiological significance. These early purported roles for TCT, first as an agent important in blood calcium regulation and later as an agent to prevent hypercalcemia, are no longer considered as physiological functions. While large supraphysiological doses of CT have an effect on the morphology and function of osteoclasts, it is unlikely that these effects of CT are important in the normal physiology of osteoclasts or bone remodeling. It is surprising that 38 years after the discovery of TCT there is no consensus as to its role in normal mammalian physiology. This editorial concerns three possibilities with respect to TCT: 1) the hormone is vestigial; 2) the hormone plays a role in water metabolism, ionic concentrations, and/or acid-base balance, actions that may not involve calcium metabolism at all; and 3) TCT acts to store phosphate postprandially on bone surfaces as a labile calcium-phosphate colloid, an action that may provide calcium needed for use in non-feeding periods or to reduce postprandial loss of phosphate when dietary phosphate is limited. Also discussed are recent publications indicating that CT synthesized in non-thyroidal tissues (NTCT) may have paracrine actions.     

Functional evolution: origin and problems

In the article the history of comparative and evolutionary physiology since the early XIX is given. The most substantial methods of evolutionary physiology are described. In the mid-50ies Orbely put forward the suggestion concerning two tasks facing evolutionary physiology, namely the study of evolution of functions and functional evolution. In the present work attention is given to the principles underlying evolution of functions on different levels of physiological systems. The main aspects of functional evolution are discussed.     

Actual Problems of Physiology of Microorganisms

Physiology of microorganisms is traditionally considered as one of branches of microbiology. Fundamental works in this field, the last of which were written almost 40 years ago, included such issues, as chemical composition, physico-chemical properties, metabolism, respiration, reproduction, and growth of microorganisms. For the last few decades, the main efforts of scientists in these fields were concentrated on decoding molecular-genetic mechanisms underlying functioning of microbial cells. At the same time, the accumulated scientific data in adjacent fields of biological science require insistently the necessity of new understanding and systematization of results of study of processes of vital activity of all species of living organisms, based on general integrative physiological principles. By the present time, it has been convincingly proved that the existence of higher organisms is impossible without constant interaction with the world of microbes and, hence, physiology of human, animals or plants is inextricably connected with physiological processes of their inhabiting microorganisms. In the present work the main actual problems of modern physiology of microorganisms are considered, and the necessity of separation of this branch of knowledge as an autonomous part of physiology is emphasized.     

Physiology in XXI century: natural science and medicine

Progress of physiology is closely connected with achievements of the adjacent sciences that developed particularly intensively at the end of the XX century. The key role in strategy of physiological investigations is played by study of the nature of regulation of individual processes providing activity of the organism as a whole. By the example of study of renal function there are discussed the issue of integration of its incretory and secretory functions, elucidation of the mechanism of activity of regulatory systems with taking into account the wide diversity of types and subtypes of receptors, interaction of numerous variants of cotransporters, pumps, water and ion channels, which eventually provides the amazing efficiency of the coordinated work of several organs and systems for stabilization of physical-chemical parameters of the internal environment. Development of physiology is of importance for progress of natural science and clinical medicine, as its achievements facilitate discovery of mechanisms of physiological functions, elucidation of defect of the locus underlying dysfunction.     

The histophysiology and pathophysiology of the peritoneum

The peritoneum is an extensive serous organ with both epithelial and mesenchymal features and a variety of functions. Diseases such as inflammatory peritonitis and peritoneal carcinomatosis can induce disturbance of the complex physiological functions. To understand the peritoneal response in disease, normal embryonic development, anatomy in healthy conditions and physiology of the peritoneum have to be understood. This review aims to summarize and discuss the literature on these basic peritoneal characteristics.The peritoneum is a dynamic organ capable of adapting its structure and functions to various physiological and pathological conditions. It is a key element in regulation of inflammatory responses, exchange of peritoneal fluid and prevention of fibrosis in the abdominal cavity. Disturbance of these mechanisms may lead to serious conditions such as the production of large amounts of ascites, the generation of fibrotic adhesions, inflammatory peritonitis and peritoneal carcinomatosis.The difficulty to treat diseases, such as inflammatory peritonitis and peritoneal carcinomatosis, stresses the necessity for new therapeutic strategies. This review provides a detailed background on the peritoneal anatomy, microenvironment and immunologic responses which is essential to generate new hypotheses for future research.     

Genomics and homeostasis

The Cannon lecture this year illustrates how knowledge of DNA sequences of complex living organisms is beginning to shape the landscape of physiology in the 21st century. Enormous challenges and opportunities now exist for physiologists to relate the galaxy of genes to normal and pathological functions. The first extensive genomic systems biology map for cardiovascular and renal function was completed last year as well as a new hypothesis-generating tool ("physiological profiling") that enables us to hypothesize relationships between specific genes responsible for the regulation of regulatory pathways. Techniques of chromosomal substitution (consomic and congenic rats) are beginning to confirm statistical results from linkage analysis studies, narrow the regions of genetic interest for positional cloning, and provide genetically well-defined control strains for physiological studies. Patterns of gene expression identified by microarray and mapping of expressed genes to chromosomal sites are adding to the understanding of systems physiology. The previously unimaginable goal of connecting approximately 36,000 genes to the complex functions of mammalian systems is indeed well underway.     

Canonical transient receptor potential 4 and its small molecule modulators

Canonical transient receptor potential 4(TRPC4) forms non-selective cation channels that contribute to phospholipase C-dependent Ca2+ entry into cells following stimulation of G protein coupled receptors and receptor tyrosine kinases.Moreover,the channels are regulated by pertussis toxin-sensitive Gi/o proteins,lipids,and various other signaling mechanisms.TRPC4-containing channels participate in the regulation of a variety of physiological functions,including excitability of both gastrointestinal smooth muscles and brain neurons.This review is to present recent advances in the understanding of physiology and development of small molecular modulators of TRPC4 channels.     

5α-Reductases In Human Physiology: an Unfolding Story

Objective5a-reductases are a family of isozymes expressed in a wide host of tissues including the central nervous system (CNS) and play a pivotal role in male sex ual differentiation, development and physiology.MethodsA comprehensive literature search from 1970 to 2011 was made through PubMed and the relevant information was summarized.Results5a reductases convert testosterone, proges terone, deoxycorticosterone, aldosterone and corticoste rone into their respective 5a-dihydro-derivatives, which serve as substrates for 3a-hydroxysteroid dehydrogenase enzymes. The latter transforms these 5a-reduced metabo lites into a subclass of neuroactive steroid hormones with distinct physiological functions. The neuroactive steroid hormones modulate a multitude of functions in human physiology encompassing regulation of sexual differen tiation, neuroprotection, memory enhancement, anxiety, sleep and stress, among others. In addition, 5a -reductase type 3 is also implicated in the N-glycosylation of pro teins via formation of dolichol phosphate. The family of 5a-reductases was targeted for drug development to treat pathophysiological conditions, such as benign prostatic hyperplasia and androgenetic alopecia. While the clinical use of 5a-reductase inhibitors was well established, the scope and the magnitude of the adverse side effects of such drugs, especially on the CNS, is still unrecognized due to lack of knowledge of the various physiological functions of this family of enzymes, especially in the CNS.ConclusionThere is an urgent need to better under stand the function of 5a-reductases and the role of neuro active steroids in human physiology in order to minimize the potential adverse side effects of inhibitors targeting 5a-reductases to treat benign prostatic hyperplasia and androgenic alopecia. (Endocr Pract. 2012;18:965-975)     

Physiological regulatory networks: ecological roles and evolutionary constraints

Ecological and evolutionary physiology has traditionally focused on one aspect of physiology at a time. Here, we discuss the implications of considering physiological regulatory networks (PRNs) as integrated wholes, a perspective that reveals novel roles for physiology in organismal ecology and evolution. For example, evolutionary response to changes in resource abundance might be constrained by the role of dietary micronutrients in immune response regulation, given a particular pathogen environment. Because many physiological components impact more than one process, organismal homeostasis is maintained, individual fitness is determined and evolutionary change is constrained (or facilitated) by interactions within PRNs. We discuss how PRN structure and its system-level properties could determine both individual performance and patterns of physiological evolution.     

Aims of undergraduate physiology education: a view from the University of Chicago

Physiology may play an important, if not essential role, in a liberal arts education because it provides a context for integrating information and concepts from diverse biological and extra-biological disciplines. Instructors of physiology may aid in fulfilling this role by clarifying the core concepts that physiological details exemplify. As an example, presented here are the core principles that are the basis for an undergraduate physiology course taught at the University of Chicago. The first of these is: Evolution has resulted in organisms comprising mechanisms for maintenance, growth, and reproduction, despite perturbations of the internal and external environment. Such principles necessitate a coupling of physiology to diverse disciplines (i.e., "sciomics") and provide a basis for integrating discoveries in other disciplines.     

论心理对生理的影响和作用

本文阐述了心理对生理的能动作用。在一定的条件下,人的心理可影响其生理功能,两者互为因果、相互影响。生理是心理活动的物质基础,心理是其生理的驱动力和标志。本文论述了精神、情绪、意念、信念、暗示等心理活动对生理的影响和作用及中医论心理对生理的作用,中医利用情志疗法的理论达到心理对生理趋向健康的作用。同时论证了肠道菌群通过心理间接影响生理功能,通过微生态制剂调节肠道菌群的微生态平衡,可改善患者的神经症状,使之心理活动达到最佳状态,进而使人的生理趋向健康。     

The novel Hha/YmoA family of nucleoid-associated proteins: use of structural mimicry to modulate the activity of the H-NS family of proteins

The Hha/YmoA family of proteins is a group of conserved, low-molecular-weight proteins involved in the regulation of gene expression. Studies performed in Escherichia coli, Salmonella sp. and Yersinia sp. highlight the contribution of these proteins in regulating bacterial virulence, horizontal gene transfer and cell physiology. Genes encoding such proteins are located on chromosomes and plasmids in different genera of Gram-negative bacteria. Their mode of action is currently being analysed by studying direct binding of Hha to DNA and as a component of protein complexes with regulatory functions. Recent data on the interaction of Hha with the H-NS family of proteins and structural information suggest a physiological role for such protein complexes in many aspects of gene regulation.     

Managing odds in stem cells: insights into the role of mitochondrial antioxidant enzyme MnSOD

Reactive oxygen species (ROS) have been poised at a straddled state of being beneficiary as well detrimental depending on its threshold levels. Maintaining the homeostasis of ROS is imperative for normal cellular physiology, wherein physiological concentrations of ROS are involved in cell signaling and elevated ROS contribute to the development of various diseases. Superoxide dismutases (SODs), enzymes involved in dismutation of superoxide anion to hydrogen peroxide, arrive as a first line of defense when there is perturbation in the homeostasis of ROS. As mitochondria are the main site of superoxide production, among SODs, mitochondrial manganese SOD (MnSOD) is the primary antioxidant enzyme that protects cells from ROS. Most importantly, knockout of MnSOD leads to postnatal lethality and tissue-specific conditional knockout in brain resulted in death of mice, conclusively portraying the essential role of MnSOD in development. Although MnSOD has been extensively discussed with the purview of tumor biology and aging, understanding the crucial role of MnSOD in stem cell physiology is still at its infant stage. Ever increasing progress in stem cell research has recently unveiled the essential role of MnSOD in self-renewal and differentiation of stem cells. In this review, we will conglomerate the current aspects by which MnSOD can contribute to embryonic stem cells’ and adult stem cells’ functions and interpret the necessity of understanding MnSOD for further stem cell mediated applications.     

NCS-1 is a regulator of calcium signaling in health and disease

Neuronal Calcium Sensor-1 (NCS-1) is a highly conserved calcium binding protein which contributes to the maintenance of intracellular calcium homeostasis and regulation of calcium-dependent signaling pathways. It is involved in a variety of physiological cell functions, including exocytosis, regulation of calcium permeable channels, neuroplasticity and response to neuronal damage. Over the past 30?years, continuing investigation of cellular functions of NCS-1 and associated disease states have highlighted its function in the pathophysiology of several disorders and as a therapeutic target. Among the diseases that were found to be associated with NCS-1 are neurological disorders such as bipolar disease and non-neurological conditions such as breast cancer. Furthermore, alteration of NCS-1 expression is associated with substance abuse disorders and severe side effects of chemotherapeutic agents. The objective of this article is to summarize the current body of evidence describing NCS-1 and its interactions on a molecular and cellular scale, as well as describing macroscopic implications in physiology and medicine. Particular attention is paid to the role of NCS-1 in development and prevention of chemotherapy induced peripheral neuropathy (CIPN).     

Phytoserotonin: A review

Serotonin (5-hydroxytryptamine; SER) is one of the well-studied indoleamine neurotransmitters in vertebrates. Recently SER has also been reported in wide range of plant species. The precise function of SER at the physiological level, particularly growth regulation, flowering, xylem sap exudation, ion permeability and plant morphogenesis in plant system has not been clear. Though SER is found in different parts of plant species including leaves, stems, roots, fruits and seeds, the quantity of SER within plant tissues varies widely. SER has been recently shown as a plant hormone in view of its auxin-like activity. This brief review provides an overview of SER biosynthesis, localization, its role in plant morphogenesis and possible physiological functions in plants. This would certainly help to elucidate further the multiple roles of SER in plant morphogenesis. In the future it may form the basis for studies on involvement of SER in cellular signaling mechanisms in plants. Apart from these gaps in understanding the role of SER in ontogeny of plant physiology and ecological, adaptations have been emphasized. Thus, overall perspectives in this area of research and its possible implications have been presented.Key words: biosynthesis, growth regulation, occurrence, physiological functions, phytoserotonin, plant morphogenesis, serotonin