scholarly journals Role of Carbonic Anhydrases and Inhibitors in Acid–Base Physiology: Insights from Mathematical Modeling

2019 ◽  
Vol 20 (15) ◽  
pp. 3841 ◽  
Author(s):  
Occhipinti ◽  
Boron
Keyword(s):  
Mathematical Modeling ◽  
Ph Regulation ◽  
Reaction Diffusion ◽  
The Body ◽  
Whole Body ◽  
Facilitated Diffusion ◽  
Carbonic Anhydrases ◽  
Physiological Processes ◽  
Urinary Acid

Carbonic anhydrases (CAs) catalyze a reaction fundamental for life: the bidirectional conversion of carbon dioxide (CO2) and water (H2O) into bicarbonate (HCO3−) and protons (H+). These enzymes impact numerous physiological processes that occur within and across the many compartments in the body. Within compartments, CAs promote rapid H+ buffering and thus the stability of pH-sensitive processes. Between compartments, CAs promote movements of H+, CO2, HCO3−, and related species. This traffic is central to respiration, digestion, and whole-body/cellular pH regulation. Here, we focus on the role of mathematical modeling in understanding how CA enhances buffering as well as gradients that drive fluxes of CO2 and other solutes (facilitated diffusion). We also examine urinary acid secretion and the carriage of CO2 by the respiratory system. We propose that the broad physiological impact of CAs stem from three fundamental actions: promoting H+ buffering, enhancing H+ exchange between buffer systems, and facilitating diffusion. Mathematical modeling can be a powerful tool for: (1) clarifying the complex interdependencies among reaction, diffusion, and protein-mediated components of physiological processes; (2) formulating hypotheses and making predictions to be tested in wet-lab experiments; and (3) inferring data that are impossible to measure.

scholarly journals Collagen drinks for functional nutrition

2018 ◽  
Vol 80 (3) ◽  
pp. 97-103
Author(s):  
L. V. Antipova ◽  
S. A. Storublevtsev ◽  
A. A. Getmanova
Keyword(s):  
Connective Tissue ◽  
Main Part ◽  
Jerusalem Artichoke ◽  
The Body ◽  
Whole Body ◽  
Energy Functions ◽  
Preventive Actions ◽  
Prevention And Treatment ◽  
Experimental Laboratory

In the process of life of the body continuously consumed nutrients that perform plastic and energy functions. The source of nutrients is a variety of foods, consisting of a complex of proteins, fats and carbohydrates, which in the process of digestion are converted into digestible substances. Collagen is the basis of connective tissue and binds the cells in the tissues, creates the frame of the whole body. The gastrointestinal tract, as a system of organs, is no exception and is designed process and extract nutrients from food. Most organs consist of connective tissue, accounting for 60–90% of their mass, which confirms its importance and the role of collagen in this regard can not be estimated. Collagen functions in the body are diverse, one of the main - part in digestion, the violation of which is the cause of diseases such as gastritis and ulcers. For the prevention and treatment of such diseases are very useful liquid collagen-containing food in the form of functional drinks. Developed and obtained in the experimental laboratory a variety of drinks on a collagen basis, with the use of additional broth with sea buckthorn pulp, tincture of dried chicory root powder and broth with the flesh of Jerusalem artichoke. An invaluable contribution to the therapeutic and preventive actions of all these components is proved not only scientifically, but also time-tested.

Pathogenesis as a problem of functional incompetence and imbalance in the population of T-lymphocytes

2021 ◽  
pp. 109-119
Author(s):  
Н.М. Геворкян ◽  
Н.В. Тишевская
Keyword(s):  
T Lymphocytes ◽  
Personalized Medicine ◽  
The Body ◽  
Lymphoid Cells ◽  
Human Diseases ◽  
Regulatory Role ◽  
Total Rna ◽  
Physiological Processes ◽  
Health And Disease

Цель обзора - анализ клеточной основы патогенеза различных заболеваний в свете регуляторной роли Т-лимфоцитов. Рассматривается роль поликлонального многообразия популяции Т-лимфоцитов, особых свойств этих клеток-представителей гомеостатической системы организма в физиологических процессах в норме и при патологии. Указаны перспективы терапевтического и профилактического воздействий, связанные с использованием суммарных РНК нормальных лимфоидных клеток аллогенной и ксеногенной природы. Указана также возможность создания с помощью лимфоцитарных суммарных РНК адекватных моделей заболеваний человека на пути к развитию персонифицированной медицины. This review provides an analysis of the cellular basis of the pathogenesis of various diseases in the light of the regulatory role of T-lymphocytes. The role of the polyclonal diversity of the population of T-lymphocytes, the special properties of these cells-representatives of the homeostatic system of the body, in physiological processes in health and disease is considered. Prospects for therapeutic and prophylactic effects associated with the use of total RNA of normal lymphoid cells of allogeneic and xenogenic origin are indicated. The possibility of creating, using lymphocytic total RNA, adequate models of human diseases for the development of personalized medicine is also indicated.

scholarly journals The Neural Regulation of Cancer

2020 ◽  
Vol 4 (1) ◽  
pp. 371-390
Author(s):  
Shawn Gillespie ◽  
Michelle Monje
Keyword(s):  
Nervous System ◽  
Crucial Role ◽  
The Body ◽  
Tissue Homeostasis ◽  
Neural Regulation ◽  
Physiological Processes

The nervous system is intimately involved in physiological processes from development and growth to tissue homeostasis and repair throughout the body. It logically follows that the nervous system has the potential to play analogous roles in the context of cancer. Progress toward understanding the crucial role of the nervous system in cancer has accelerated in recent years, but much remains to be learned. Here, we highlight rapidly evolving concepts in this burgeoning research space and consider next steps toward understanding and therapeutically targeting the neural regulation of cancer.

Role of facilitated diffusion of calcium by calbindin in intestinal calcium absorption

1992 ◽  
Vol 262 (2) ◽  
pp. C517-C526 ◽  
Author(s):  
J. J. Feher ◽  
C. S. Fullmer ◽  
R. H. Wasserman
Keyword(s):  
Negative Feedback ◽  
Calcium Absorption ◽  
Feedback Inhibition ◽  
Basolateral Membrane ◽  
Reaction Diffusion ◽  
Diffusion Problem ◽  
Facilitated Diffusion ◽  
Calbindin D9k ◽  
And Diffusion

Computer simulations of transcellular Ca2+ transport in enterocytes were carried out using the simulation program SPICE. The program incorporated a negative-feedback entry of Ca2+ at the brush-border membrane that was characterized by an inhibitor constant of 0.5 microM cytosolic Ca2+ concentration ([Ca2+]). The basolateral Ca(2+)-ATPase was simulated by a four-step mechanism that resulted in Michaelis-Menten kinetics with a Michaelis constant of 0.24 microM [Ca2+]. The cytosolic diffusion of Ca2+ was simulated by dividing the cytosol into 10 slabs of equal width. Ca2+ binding to calbindin-D9K was simulated in each slab, and diffusion of free Ca2+, free calbindin, and Ca(2+)-laden calbindin was simulated between each slab. The cytosolic [Ca2+] of the simulated cells was regulated within the physiological range. Calbindin-D9K reduced the cytosolic [Ca2+] gradient, increased Ca2+ entry into the cell by removing the negative-feedback inhibition of Ca2+ entry, increased cytosolic Ca2+ flow, and increased the efflux of Ca2+ across the basolateral membrane by increasing the free [Ca2+] immediately adjacent to the pump. The enhancement of transcellular Ca2+ transport was nearly linearly dependent on calbindin-D9K concentration. The values of the dissociation constant (Kd) for calbindin-D9K were previously obtained experimentally in the presence and absence of KCl. Calbindin with the Kd obtained in the presence of KCl enhanced the simulated Ca2+ transport more than with the Kd obtained in the absence of KCl. This result suggests that the physiological Kd of calbindin is optimal for the enhancement of transcellular Ca2+ transport. The simulated Ca2+ flow was less than that predicted from the "near-equilibrium" analytic solution of the reaction-diffusion problem.

Physiological effects of endogenous ouabain: control of intracellular Ca2+ stores and cell responsiveness

1993 ◽  
Vol 264 (6) ◽  
pp. C1367-C1387 ◽  
Author(s):  
M. P. Blaustein
Keyword(s):  
Steady State ◽  
Cell Types ◽  
Whole Body ◽  
Cellular Mechanisms ◽  
Signaling Mechanism ◽  
Physiological Processes ◽  
Endogenous Ouabain ◽  
Adrenal Cortical Hormone ◽  
Salt And Water Balance

Ouabain is a well-known compound but a newly discovered adrenal cortical hormone that plays a role in cell Na+ regulation and in whole body salt and water balance. Ouabain may also be a paracrine hormone and may be secreted by some central nervous system neurons as well as by other types of cells. This article focuses on the cellular mechanisms that underlie the physiological (and pathophysiological) effects of ouabain. Ouabain directly inhibits the plasmalemmal Na+ pump in a variety of cell types. Low ouabain concentrations cause, in the steady state, a modest rise in the cytosolic Na+ concentration but only a minimal decline in membrane potential. All Na+ gradient-dependent processes may thereby be affected, albeit to only a small extent. Most important, however, is the secondary redistribution of Ca2+, mediated by Na(+)-Ca2+ exchange, that should slightly increase the cytosolic free Ca2+ concentration ([Ca2+]cyt). As a result of Ca2+ sequestration in intracellular stores [the endoplasmic and/or sarcoplasmic reticulum (ER/SR)], however, a new steady state is achieved with a slightly increased [Ca2+]cyt but a substantially augmented Ca2+ store; thus the ER/SR effectively acts as a Ca2+ amplifier. This extra stored Ca2+ is then available for mobilization whenever the cells are activated. Cytosolic Ca2+ is a key signaling mechanism in virtually all cells: it controls numerous physiological processes such as contraction, secretion, and excitability. Thus ouabain may modulate cell responsiveness via its influence on ER/SR Ca2+ stores. With these principles in mind, we examine evidence that endogenous ouabain may play a role in numerous physiological and pathophysiological processes associated with altered fluid and electrolyte metabolism and deviations from the normal blood pressure-blood volume relationship. We discuss the possible participation of ouabain in the regulation of vascular tone and then consider the putative role of ouabain in several forms of hypertension, congestive heart failure, thyroid and adrenocortical dysfunction, and diabetes mellitus, as well as in the adaptation to high altitude.

Renal interstitial hyaluronan: functional aspects during normal and pathological conditions

2012 ◽  
Vol 302 (11) ◽  
pp. R1235-R1249 ◽  
Author(s):  
Sara Stridh ◽  
Fredrik Palm ◽  
Peter Hansell
Keyword(s):  
Current Knowledge ◽  
Stone Formation ◽  
Ischemia Reperfusion ◽  
The Body ◽  
Receptor Expression ◽  
Whole Body ◽  
Hydration Status ◽  
Hyaluronan Synthases ◽  
Pathological Conditions

The glycosaminoglycan (GAG) hyaluronan (HA) is recognized as an important structural component of the extracellular matrix, but it also interacts with cells during embryonic development, wound healing, inflammation, and cancer; i.e., important features in normal and pathological conditions. The specific physicochemical properties of HA enable a unique hydration capacity, and in the last decade it was revealed that in the interstitium of the renal medulla, where the HA content is very high, it changes rapidly depending on the body hydration status while the HA content of the cortex remains unchanged at very low amounts. The kidney, which regulates fluid balance, uses HA dynamically for the regulation of whole body fluid homeostasis. Renomedullary HA elevation occurs in response to hydration and during dehydration the opposite occurs. The HA-induced alterations in the physicochemical characteristics of the interstitial space affects fluid flux; i.e., reabsorption. Antidiuretic hormone, nitric oxide, angiotensin II, and prostaglandins are classical hormones/compounds involved in renal fluid handling and are important regulators of HA turnover during variations in hydration status. One major producer of HA in the kidney is the renomedullary interstitial cell, which displays receptors and/or synthesis enzymes for the hormones mentioned above. During several kidney disease states, such as ischemia-reperfusion injury, tubulointerstitial inflammation, renal transplant rejection, diabetes, and kidney stone formation, HA is upregulated, which contributes to an abnormal phenotype. In these situations, cytokines and other growth factors are important stimulators. The immunosuppressant agent cyclosporine A is nephrotoxic and induces HA accumulation, which could be involved in graft rejection and edema formation. The use of hyaluronidase to reduce pathologically overexpressed levels of tissue HA is a potential therapeutic tool since diuretics are less efficient in removing water bound to HA in the interstitium. Although the majority of data describing the role of HA originate from animal and cell studies, the available data from humans demonstrate that an upregulation of HA also occurs in diabetic kidneys, in transplant-rejected kidneys, and during acute tubular necrosis. This review summarizes the current knowledge regarding interstitial HA in the role of regulating kidney function during normal and pathological conditions. It encompasses mechanistic insights into the background of the heterogeneous intrarenal distribution of HA; i.e., late nephrogenesis, its regulation during variations in hydration status, and its involvement during several pathological conditions. Changes in hyaluronan synthases, hyaluronidases, and binding receptor expression are discussed in parallel.

scholarly journals Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism

2021 ◽  
Vol 9 ◽  
Author(s):  
Dianne M. Perez
Keyword(s):  
Adrenergic Receptors ◽  
Smooth Muscle Contraction ◽  
The Body ◽  
Whole Body ◽  
Selective Ligands ◽  
Recent Developments ◽  
Vascular Smooth Muscle Contraction ◽  
G Protein Coupled ◽  
Similar Affinity

The α1-adrenergic receptors (ARs) are G-protein coupled receptors that bind the endogenous catecholamines, norepinephrine, and epinephrine. They play a key role in the regulation of the sympathetic nervous system along with β and α2-AR family members. While all of the adrenergic receptors bind with similar affinity to the catecholamines, they can regulate different physiologies and pathophysiologies in the body because they couple to different G-proteins and signal transduction pathways, commonly in opposition to one another. While α1-AR subtypes (α1A, α1B, α1C) have long been known to be primary regulators of vascular smooth muscle contraction, blood pressure, and cardiac hypertrophy, their role in neurotransmission, improving cognition, protecting the heart during ischemia and failure, and regulating whole body and organ metabolism are not well known and are more recent developments. These advancements have been made possible through the development of transgenic and knockout mouse models and more selective ligands to advance their research. Here, we will review the recent literature to provide new insights into these physiological functions and possible use as a therapeutic target.

scholarly journals MicroRNAs as Important Regulators Mediate the Multiple Differentiation of Mesenchymal Stromal Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Chao Yang ◽  
Maowen Luo ◽  
Yu Chen ◽  
Min You ◽  
Qiang Chen
Keyword(s):  
Regenerative Medicine ◽  
Stromal Cells ◽  
Critical Role ◽  
The Body ◽  
Disease Treatment ◽  
Multipotent Stem Cells ◽  
Physiological Processes ◽  
Multiple Differentiation ◽  
Differentiation Efficiency

MicroRNAs (miRNAs) are endogenous short non-encoding RNAs which play a critical role on the output of the proteins, and influence multiple biological characteristics of the cells and physiological processes in the body. Mesenchymal stem/stromal cells (MSCs) are adult multipotent stem cells and characterized by self-renewal and multidifferentiation and have been widely used for disease treatment and regenerative medicine. Meanwhile, MSCs play a critical role in maintaining homeostasis in the body, and dysfunction of MSC differentiation leads to many diseases. The differentiation of MSCs is a complex physiological process and is the result of programmed expression of a series of genes. It has been extensively proven that the differentiation process or programmed gene expression is also regulated accurately by miRNAs. The differentiation of MSCs regulated by miRNAs is also a complex, interdependent, and dynamic process, and a full understanding of the role of miRNAs will provide clues on the appropriate upregulation or downregulation of corresponding miRNAs to mediate the differentiation efficiency. This review summarizes the roles and associated signaling pathways of miRNAs in adipogenesis, chondrogenesis, and osteogenesis of MSCs, which may provide new hints on MSCs or miRNAs as therapeutic strategies for regenerative medicine and biotherapy for related diseases.

scholarly journals mTOR Pathway is Involved in Energy Homeostasis Regulation as a Part of the Gut–Brain Axis

2020 ◽  
Vol 21 (16) ◽  
pp. 5715
Author(s):  
Veronica Pena-Leon ◽  
Raquel Perez-Lois ◽  
Luisa Maria Seoane
Keyword(s):  
Energy Homeostasis ◽  
The Body ◽  
Mtor Signaling ◽  
Physiological Processes ◽  
Energy Sensor ◽  
Relevant Role ◽  
Regulate Food Intake ◽  
Glucose And Lipid Homeostasis ◽  
Treatment Of Obesity

Mammalian, or mechanic, target of rapamycin (mTOR) signaling is a crucial factor in the regulation of the energy balance that functions as an energy sensor in the body. The present review explores how the mTOR/S6k intracellular pathway is involved in modulating the production of different signals such as ghrelin and nesfatin-1 in the gastrointestinal tract to regulate food intake and body weight. The role of gastric mTOR signaling in different physiological processes was studied in depth through different genetic models that allow the modulation of mTOR signaling in the stomach and specifically in gastric X/A type cells. It has been described that mTOR signaling in X/A-like gastric cells has a relevant role in the regulation of glucose and lipid homeostasis due to its interaction with different organs such as liver and adipose tissue. These findings highlight possible therapeutic strategies, with the gut–brain axis being one of the most promising targets in the treatment of obesity.

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