Search

A wide range of differences of cations concentrations (Na, K, Ca, Mg) in hemolymph, blood serum of multicellular animals and humans was revealed. It was established that constancy of K/Na ratio 0.034 +/- 0.001 is strictly maintained in these organisms. Except for some freshwater and marine organisms, Mg/Na ratio is sustained on the same level in the wide range of concentrations of these ions in serum of vertebrates and hemolymph of invertebrates. Ca/Na ratio is higher in hemolymph of freshwater mollusks. The question about possible reasons of physiological differences of Ca/Na and Mg/Na rations compared to constancy of K/Na ratio is discussed.

Solute-free water clearance increased by 186% in water loaded rats treated with glucagon-like peptide 1 compared to untreated group. The effect of glucagon-like peptide 1 was reproduced in experiments with its synthetic analogue exenatide. Serum osmolality in water loaded rats treated with exenatide was closer to normal level on 30, 45, 60 min of experiment compared to the untreated group and reached the control value in 60 min. Administration of glucagon-like peptide 1 receptor antagonist to water loaded rats delayed (5 ml per 100 g bw) or prevented (2 ml per 100 g bw) increase in solute-free water clearance. The obtained data suggest the involvement of glucagon-like peptide 1 in osmotic homeostasis and indicate the unique physiologic role of incretins in regulation of water balance.

The investigation deals with effect of analogues of conopressin S--a peptide of the vasopressin family with amino acid replacement in the 2nd and 4th positions (characteristic of invertebrate peptides)--on transport of water and ions in the rat kidney. At administration to female Wistar rats, 1-deamino-conopressin S produced a weak action on water transport and had no effect on urinary K+ and Na+ excretion. Its analogue, 1-deamino-Tyr2-conopressin S, caused antidiuretic and kaliuretic action without affecting the Na+ excretion. Estimation of significance of the variant of optic isomer of arginine in the 4th and 8th position of the molecular for the antidiuretic and kaliuretic action of the peptide showed that 1-deamino-Tyr2,D-Arg4-conopressin S and 1-deamino-Tyr2,D-Arg4,8-conopressin S did not affect the urinary K+ excretion and renal water reabsorption, whereas action of 1-deamino-Tyr2,D-Arg8-conopressin S did not differ from action of 1-deamino-Tyr2-conopressin S. Thus, it has been established that the selective kaliuretic action of analogues of conopressin S on rat kidney depends on the presence of tyrosine in the 2nd and of L-arginine, but not of D-arginine, in the 4th position of the molecule.

Exenatide effect was studied in 55 human including 38 patients with type 2 diabetes mellitus without signs of diabetic nephropathy and primary renal diseases. Preliminary study with water load in volume from 0.5 to 1% b.w. showed that water load equal to 0.7% b.w. caused significant increase in urine excretion. The rise of diuresis after 10 microg Byetta (exenatide) injection and simultaneous water load of 0.7% of b.w. depended on increase in solute-free water clearance. Thus, exenatide (mimetic of GLP-1) action let us to consider its possible role as component of osmoregulation system in human. This peptide provides high efficiency of renal function in osmotic homeostasis.

Leaching of granitoids of the paleoproterozoic age was performed from several seconds to 360 days in water solutions (pH < 6.0) in the oxygen or argon medium. Under these conditions the entrance of K+ into the solution has been shown to occur at the higher rate than that of Na+. The obtained data are considered as evidence in favor of a possibility of the existence at the earlier stages of the Earth geologic history of water reservoirs with predominance of K+ over Na+. The K+/Na+ ratio exceeding 1 has been shown in prokaryotes, in cells and tissues of the free living and parasitic species of invertebrate and vertebrate animals. At the same time in the extracellular fluid of the fresh water, marine, and terrestrial animals, in which the Na+ concentration varies from 13 to 482 mmol/l, the K+/Na+ ratio is preserved at the level of 0.034 +/- 0.001. These results are discussed in connection with the problem of origin of protocells and of concentration ratios of monovalent cations in water phases of multicellular organisms.

We compared parameters of water-salt balance in Wistar female rats fed normal chows during more than 2 weeks. Potassium content was 1.4-fold higher in diet I than in diet II, and sodium end water content was 3.3- and 7.5-fold higher in diet II than in diet I. Blood osmolality and concentration of Na+, K+, Mg2+ were equal in rats fed different chow. In water-loaded rats (5 ml of water/100 bw per os) fed different chow, urine flow rate did not differ, but solute-free water excretion was higher by 40.2% in the rats fed diet II vs. diet I. The sort of diet did not affect the renal sodium excretion during oral administration of 5 ml 0.9% NaCl per 100 g bw to rats. After vasopressin injection solute-free water reabsorption was 1.5-fold higher in rats fed diet II. Natriuretic and hydruretic effect of exenatide, glucagon-like peptide 1 mimetic, was weaker in rats fed diet I. The data obtained indicate that organism can effectively maintain blood parameters. The modulation of hormone regulatory effects on water and sodium balance was found to depend on the state of organism under diet consumed continuously.

Exenatide injection to female Wistar rats induced an increase in diuresis, urinary sodium and mild potassium excretion. The maximum natriuretic effect of exenatide was 18500 times more pronounced compared to that of furosemide in equimolar dose. The natriuretic and diuretic effects after combined administration of maximum doses of exenatide and furosemide were additive, which was indicative of different mechanisms of their action on the nephron. Exenatide probably inhibits sodium reabsorption in renal proximal segment. The data obtained might be essential for assessment of the clinical use of exenatide to excrete extracellular fluid excess in cases of edemation and to maintain potassium balance.

Efficacy of drugs reduced proximal reabsorption was compared in experiments with female Wistar rats. Urine flow rate for the 1st h of experiment was enhanced after polyethylene glycol-400 (PEG) and 6% Na2SO4 infusion by over 30-fold, exenatide--40-fold, glycerol--11-fold as compared with the control. The maximal values of Na+ excretion were observed during Na2SO4 and exenatide administration (280 +/- 31 micromol/h vs. 3.2 +/- 0.6 Imol/h/100 g bw). The highest K+ excretion was revealed in experiments with glycerol administration (41 +/- 5 micromol/h vs. 7 +/- 2 micromol/h/100 g bw), Mg2+ --after exenatide injection (5.3 +/- 1.3 micromol/h vs. 0.16 +/- 0.03 micromol/ h/100 g bw). Diuretic effects were additive after combined administration of maximal doses of exenatide and PEG which suggests a different mechanism of action of solutes filtrated (PEG) to the proximal nephron segment and generated due to Na+/HW-exchange inhibition (exenatide). Osmotic diuretics differ by potency, mechanism of diuretic action and selectivity of ion excretion).

The calculated values of the binding energy of nonapeptides with receptors in docking with their influence on reabsorption of osmotically free water in a rat bud in vivo were compared. Vasotocin and some its analogs were intramuscularly introduced to non-narcotized rat females of the Wistar line in doses from 0.1 pmol to 0.5 nmol/kg of body weight against the background of peroral water load (50 ml/kg of body weight). A significant correlation between the calculated interaction energy of peptides with V2-receptors and an increase of reabsorption of osmotically free water in the rat bud stimulated by injection of nonapeptides was found. The results evidence that alterations in rat bud in vivo caused by analogs of vasotocin and their interactions with V2-receptors can be accurately simulated.

We have developed an imitation model of the appearance of regulation of physiological functions of protocell at the initial stages of evolution of living system. It is based on suggestion of the appearance of signal function in spontaneously formed products of partial hydrolysis of the protocell polypeptides, based on which there appear the regulatory molecules--quanta of regulation. For construction of the model, the mathematical apparatus of final automats and of genetic algorithm is used. The model has demonstrated the positive role of involvement of regulatory peptides in the system of regulation of protocell functions to provide its viability under the changing envelopment conditions.

In October, 2011 120 years from the birth day of the great surgeon acad. USSR Ac. Med. Sci. S.S. Judin. Article include data on S.S.Judin's work and his life in Novosibirsk, new materials of the biography of the great surgeon, original photos.

Evolution of living organisms is closely connected with evolution of structure of the system of regulations and its mechanisms. The functional ground of regulations is chemical signalization. As early as in unicellular organisms there is a set of signal mechanisms providing their life activity and orientation in space and time. Subsequent evolution of ways of chemical signalization followed the way of development of ways of delivery of chemical signal and development of mechanisms of its regulation. The mechanisms of chemical regulation of the signal interaction is discussed by the example of the specialized system of transduction of signal from neuron to neuron, of effect of hormone on the epithelial cell and modulation of this effect. These mechanisms are considered as the most important ways of the fine and precise adaptation of chemical signalization underlying functioning of physiological systems and organs of the living organism.

Physiology studies the functions of different organs, systems and how they maintain the integrity of organisms. Nervous and endocrine systems react to stimulus, causality plays a key role in their activities. Physical and chemical conditions of fluids in the internal environment serve as a background and an active modulator for regulatory influences. Autacoid formation is in many respects based on probable events. It has been proved, that during the formation of regulatory systems in cell evolution the appearance of regulatory molecules was based on statistical probability of quantum events: sporadical appearance in cells during metabolism of peptides, lipids, hydrolysis of larger molecules on fragments, quanta, which received physiological activity in the form of function regulators. These processes in their adapted, according to Darwin's mechanism of natural selection, value were recorded into the genome since synthesis readings of the polypeptides were fixed. The formation of multicellular organisms was promoted by the arise of regulatory systems and their integration under the supervision of the nervous system.

New analogs of some neurohypophyseal hormones (oxypressin, hydrin, glumitocin, vasotocin) have been synthesized. Experiments with injection of these peptides to rats showed that substitution of C-terminal glycinamide on beta-ethanolamine (glycinol) or ethylamine in 1-deamino-arginine vasotocin resulted in loss of natriuretic but not antidiuretic activity. Analogs of oxypressin and hydrin exhibited neither natriuretic activity nor ability to affect water reabsorption. Glumitocin analog induced renal sodium ion excretion and did not influence potassium ion excretion.

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 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.

Participation of kidney in maintenance of constancy of parameters of the organism internal medium is connected with formation in it of physiologically active substances. They are components of systems of regulation of water-salt balance, arterial pressure, blood coagulation, erythropoiesis. Mechanisms of normalization by kidney of concentration of hormones in blood and of modulation of action of hormones are analyzed.

Injections of furosemide at a dose of 0.3 micromol per 100 g body weight or 1-deamino-arginine-vasotocin (1dAVT) at a dose of 0.05 nmol per 100 g body weight induced nearly equal increase in urinary sodium excretion: up to 406 +/- 20 and 405 +/- 23 micromol/2 h, respectively. Increase in urinary sodium excretion after injection of 1d-AVT was followed by enhancement of solute free water reabsorption from -0.51 +/- 0.05 to -2.75 +/- 0.11 ml/2 h (p < 0.05). On the contrary, furosemide injection induced a significant decrease in solute free water reabsorption to -0.19 +/- 0.06 ml/2 h (p < 0.05) and led to the appearance of solute free water in urine during peak of diuretic reaction. These data for the first time show that furosemide not only decreases sodium reabsorption, but also blocks some componentin molecular mechanism of vasopressin-dependent increase of the osmotic permeability of water.

Influence of enalaprilat, angiotensin converting enzyme inhibitor, on a functional proteinuria associated with increase in diuresis unduced by furosemide, 1-deamino-arginine vasotocin (1d-AVT) injection or water loading was investigated in experiments with Wistar rats. Intraperitoneal injection of 0.1 mg/100 g b.w. of enalaprilat resulted in reduction of glomerular filtration rate, solute-free water reabsorption and solutes excretion, particularly potassium excretion, after 1d-AVT administration and decrease in diuresis and solute-free water excretion after oral water loading. Enalaprilat injection did not influence on the level of proteinuria induced by the various types ofdiuresis and albuminuria during water diuresis and 1d-AVT-dependent saluresis. The data obtained have shown that decrease in angiotensin II production in the renal structures does not affect protein excretion rate during examined forms of proteinuria and suggest existence of a multicomponent system of the pressure stabilization in the glomerular apparatus.

Analogues ofarginine vasotocin with replacement of amino acids in 4, 7 and 8 positions of the hormone were synthesized. After water loading the injection of 1 x 10(-12) mol per 100 g BW 1-deamino-8-homoarginine vasotocin, 1-deamino-4-threonine-8-arginine vasotocin and 1-deamino-4-threonine-8-D-arginine vasotocin increased solute-free water reabsorption, but did not affect cations excretion (Na, K, Ca, Mg). Presence of glycine in 9th position and proline in 7th position ofa vasotocin molecule is essential for hormone interaction with a V2-receptor. In rats, injection of 5 x 10(-11) mol 1-deamino-8-homoarginine vasotocin or 1-deamino-4-threonine-8-arginine vasotocin dramatically increased urinary sodium and potassium excretion and enforced osmotically free water reabsorption but very little affected urinary magnesium and calcium excretion. The injection in the same dose of other synthesized vasotocin analogues did not affect the cations excretion. The issue of physiological mechanisms of kidney's selective response related to water, one- and bivalent cations excretion after injection of vasotocin analogues is discussed. Inhibition of cations transport is associated with activation of any V-receptor (but not V2-receptor). This effect takes place only in presence of L-arginine instead of D-arginine in the analogue.

After 12 days on space fight, body mass of gerbils decreased by 32.9%; however, the effective systems of regulation did not let changes in the concentration of Na, K, Mg ions in fresh samples of the renal cortex. These data are viewed as a reflection of the regulation systems strategy to preserve the optimal conditions for functioning of the kidney, a vital body organ. The cations were reduced significantly in the renal medulla when calculated for dry mass and compared with the synchronous control. This could have changed the osmoregulating function of the kidney during space fight and, due to small cations accumulation, caused the drop of the cortex/medulla osmotic gradient. Locations of V1a-, V1b- and V2-receptors and aquaporin 1 and 2 in renal tubule cells of gerbils before and fight are described.

Introduction in stomach of unanaesthetized healthy rats of 5 ml per 100 g BW water or an injection of 0.05-0.1 nmol per 100 g BW arginine vasotocin and its analogues led to increase of diuresis and urine protein excretion. Excretion of proteins increased from 132 +/- 78 to 365 +/- 80 microg at water loading (p < 0.01) and to 423 +/- 143 microg after injection 1-desamino-8-arginine vasotocin (p < 0.01). Direct dependence was revealed between increase of diuresis and renal protein excretion. At water loading and an injection of arginine vasotocin and its analogues, protein excretion reached close maximum values despite distinctions of force and the mechanism of diuretic effects of applied factors. The assumption was substantiated, that increase of renal protein excretion in both variants of experiments depends on change of conditions of protein filtration in glomerular apparatus of the kidney due to increasing of efferent arterioles tonus.

Evolutionary physiology as independent direction of physiology was formed in the XX century and was rapidly developing in its second half. To evaluate some tendencies of this process, we analyzed publications in Journal of Evolutionary Biochemistry and Physiology, one of the leading specialized periodicals on this problem. Analysis of works published for 4 decades has shown that the majority of papers deals with study of evolution of function of the nervous system (40-60 papers per year), less papers concern study of functions of sensory and visceral systems (20-30 per year). Among the used method, the most widely spread is the comparative-physiological method. By the end of the 1990s the number of works with use of methods of embryophysiology decreased. In the performed studies, predominant are physiological methods. Use of biochemical methods decreased, while of methods of molecular biology increased. The most often used objects of studies were mammals. By the end of the XX--beginning of the XXI century, in the greater number of papers the object of study has become human, while the number of publications in which experiments were performed on amphibians, reptiles, and birds decreased. More than a half of all works were carried out in St. Petersburg (Leningrad); the number of papers submitted from Moscow institutions gradually decreased, but the number of works from regions of Russia rose. Most studies were performed at institutes of the Russian Academy of Sciences and universities, while the number of papers from institutes of the Russian Academy of Medical Sciences decreased. For the last few years, several generalizations on evolution of functions and functional evolution have been formulated; handbooks and monographs on problems of evolutional physiology have been published.

In 19th century and at the beginning 20th century, reports appeared in the field of comparative and ontogenetic physiology and the value of these methods for understanding of evolution of functions. The term "evolutionary physiology" was suggested by A. N. Severtsov in 1914. In the beginning of 30s, in the USSR, laboratories for researches in problems of evolutionary physiology were created, the results of these researches having been published. In 1956 in Leningrad, the Institute of Evolutionary Physiology was founded by L. A. Orbeli. He formulates the goals and methods of evolutionary physiology. In the following half a century, the evolutionary physiology was actively developed. The evolutionary physiology solves problems of evolution of function of functions evolution, often involving methods of adjacent sciences, including biochemistry, morphology, molecular biology.

A dynamic imitational model is developed of initial stages of cell evolution based on role of environmental cation concentration. The model is developed on our hypothesis, concerning the medium of the appearance of protocells. Could be potassium water reservoirs rather than sea salt water with its predominance of sodium salts. The necessary elements of appearance the protocells served organic molecules, code of their synthesis, and formation of macromolecules under favorable ion concentration in environment High K+ and Mg2+ concentration and bow Na+. The model is based on an assumption that one of the first stages in evolution of life was the appearance in potassium-magnesium water reservoirs of organic molecules capable for selfreplication on the basis of genetic code and formation of protocells with potassium cytoplasm. The model has demonstrated necessity of formation of cell envelope for development of the protocell. Replacement of the dominant cation in water reservoirs-potassium by sodium-required the appearance of ion-transporting devices in plasma membrane and their participation in adaptation of cells to environment. This stage of evolution was accompanied by the most important morpho-functional event--formation of the plasma membrane instead of cell envelope. The membrane provided the ion asymmetry in the cell (preservation of K+ in it) relatively to the sodium external medium for maintaining optimal intracellular medium. In the model system, predecessors of animal cells elaborated mechanism of maintenance of the potassium cytoplasm with the sodium counter-ion dominating in the environment.

The physiology throughout centuries was considered as the basic fundamental science in medicine. Rapid development of molecular biology, genetics and of some other natural sciences in 2nd half XX demanded century not only the answer to a question on the sciences defining the base of development of medicine, but also key problems of its progress. The biomedicine is formed, its methods are discussed, is frequent in system of natural sciences, parities with physiology. The special attention is given unconditional necessity of finding-out of molecular mechanisms of functions, targets of action of physiologically active substances and obligatory correlation of data of modeling with the same processes in conditions in vivo in whole body. The role of various sciences in the decision of fundamental problems of medicine, a place and role of physiology in modern medicine is shown.

Experiments on rats showed that the intramuscular injections of arginine-vasotocin (AVT), 1-deamino-arginine-vasotocin (1dAVT) or 1-deamino-1-monocarba-arginine-vasotocin (1dlmcAVT) at a dose of 5 x 10(-11) mole per 100 g body weight increase renal excretion of Na+, K+, and Mg2+. Antagonist of V1 receptors (OPC-21268) decreases the effect of 1dAVT nonapeptides on renal excretion of the studied ions. A model of VIb-receptor is constructed and a correlation is shown between the energy of interaction of the V1b-receptor and the natriuretic effect of the studied vasotocin analogs.

In 2007, L. A. Orbeli would have been 125. He was distinguished by extremely wide scientific interrests; he created one of the most numerous and fruitful scientific schools. He authored prominent achievements in physiology of autonomic nervous system, evolutionary physiology, sensory physiology, renal physiology, physiology of underwater labor. Orbeli paid much attention to the scientific-organizational activity, he was academician-secretary of the Division of Biological Sciences of the USSR Academy of Sciences, President of the Society of Physiologists, Biochemists and Pharmacologists, Editor-in-Chief of the USSR Physiological Journal, etc. Principles of the scientific scholl founded by Orbeli are service to science and society, propity to scientific ethics, humanity.

In experiments on non-anesthetized female Wistar rats, it has been shown that injection of 1-deamino-arginine-vasotocin (1dAVT) increases sodium excretion and solute-free water reabsorption. Antagonists of V1-receptors (OPC-31260, Otsuka Pharmaceutical Co., Ltd., Japan) eliminates the effect water reabsorption whereas antagonist of V1-receptors (OPC-21268, Otsuka Pharmaceutical Co., Ltd., Japan) decreases the 1dAVT-dependent increase of Na+ and water excretion. A model of V1-receptors an a supposed topography of their interaction with 1dAVT are constructed.

A model is developed of evolution of an organism with digestive, respiratory, circulatory, and excretory systems at the single system. The model is realized on the basis of the language STELLA 8.0. A balance is found between perfection of each individual physiological system and necessary energy expenditures for survival of the organism as a whole. The model is based on a coupled development of several visceral systems. There is analyzed effect of a change of consumption of substances with food and of oxygen amount on their oxidation, a branching of blood flow to organs, specifically to kidneys, to excrete final products of metabolism from blood. The energy expenditures for circulation are believed to be proportional to blood flow in a given organ. An increase of efficiency of renal excretion from blood of final metabolic products and toxic substances has a favorable effect on inner medium and activity of each cell of an individual, but increases of the organism energy expenditures. Interrelation of these factors under conditions of adaptation to changing environmental conditions determines peculiarities of evolution of each physiological system in an individual.

The issue of the content of physiology as science, its methods, directions of modern physiology, and its place in the system of life sciences is discussed. Structure of the system of regulations, the role of endocrine system and autacoids in particular, and physiological significance of homeostasis are analyzed in detail. Problems are considered concerning the applied significance of physiology, interaction of universities and research institutions, organization ofphysiological studies in Russia. Data on members in the regional divisions of Pavlov Physiological Society are presented.

In experiments of the 5, 12 and 25-day old rat pups and adult rats in has been shown that after administration of yellow fluorescent protein (YFP) into stomach, its partial absorption in the non-degraded state in the small intestine takes place, with subsequent transport to kidney with blood flow and accumulation in cells of the proximal nephron segment. With age of rats, intensity of the intestinal YFP absorption decrease; the YFP accumulation in the kidney is more active in rats of the younger age groups than in adult animals. No accumulation of YFP in liver was revealed. The obtained data indicate an intensive absorption of YFP in the non-hydrolyzed form in the rat pup small intestine in early postnatal ontogenesis and an important role of kidney in protein metabolism and in proteolysis of exogenous proteins.

In experiments on non-anesthetized rats with administration into stomach of water (5 ml/100 g body mass) direct correlation has been found between an increase of diuresis and excretion of solute free water (r = 0.98, p < 0.01), while after injection to these animals of 5 x 10(-11) M arginine-vasotocin - between an increase of diuresis and simultaneous rise reabsorption of solute free water (r = 0.8, p < 0.01). The rise of diuresis after the vasotocin injection is due to inhibition of sodium re- absorption, with the solute excretion fraction increasing from 2.6 +/- 0.2 % to 11.9 +/- 1.2, p < 0.001. A similar physiological paradox - an increase of diuresis with the simultaneous increase of reabsorption of solute free water - has been revealed at night hours in children with tendency for nocturnal enuresis (r = 0.64, p < 0.01). Mechanism responsible for this phenomenon consists in a rise of diuresis due to a decrease of sodium ion reabsorption in the ascending Henle loop limb. A problem is discussed of the homeostatic significance of a decrease of sodium reabsorption combined with an increase of solute-free water reabsorption; it is suggested that this phenomenon is based on a redistribution of reabsorption inside the nephron - a decrease of ion and water reabsorption in the initial parts of the nephron distal segment and an increase of solute free water reabsorption with the antidiuretic hormone-stimulated high osmotic permeability of terminal parts of renal tubules. An intraperitoneal injection of V1-anatagonist (OPC-21268) decreased the natriuretic component of response to arginine-vasotocin, while injection of V2-antagonist (OPC-31260) eliminated the antidiuretic component.

Experiments on different bivalve and gastropod species living in fresh, brackish, and sea water of different salinity demonstrated a direct correlation between the osmolality of the hemolymph and interstitial fluid and the concentration of sodium ions in it. A direct correlation between the osmolality of the interstitial fluid and the content of potassium and magnesium ions in the tissues (adductor and foot) was revealed. The significance of physicochemical indices of the environment and formation of eukaryotic cells at the initial stages of animal evolution are discussed.

One of the key physiological problems of evolution is elucidation of the role of environmental inorganic factors in origin of life. A statement is substantiated that a highly significant event in evolution of life was the appearance of protocells with the K cytoplasm in K water reservoirs with their subsequent adaptation to the environment in which Na dominated. This step was accompanied by replacement of the cell envelope with the cell plasma membrane. Precursors of animals' elaborated mechanism of maintenance of the K-cytoplasm with Na-counterkation in the environment. In plants, Na remains a trace element, in animals the Na and K contents are approximately equal, but they are present in different fluid phases. In animals presence of Na+ in the external medium, K+ inside cells has become an initial pre-requisition for electrogenesis and appearance of asymmetrical cells. Electrogenesis of these cells has become a physiological pre-requisition for cell differentiation, the appearance of the nerve cell. Asymmetrical cell has provided development of absorption, digestion, excretion, respiration. Formation of the inner medium has become a prerequisite for establishment of homeostasis. Serum osmolality, sodium concentration, pH, Ca2+ are the most rigidly maintained constants in the blood serum of humans.

The circadian rhythm of urine formation was studied in younger (27 +/- 8 yr) and aged (76 +/- 3 yr) males. In 11 younger healthy examined persons a decrease of diuresis during the night as compared with the day time was due to a rise of solute free water reabsorption. In 31 aged males the change of the urine formation rhythm with increase of the nocturnal diuresis is based on a rise of osmolal clearance combined with an increase of the solute free water reabsorption. It is shown that blockade of autacoid secretion leads to normalization of the diuresis circadian rhythm. In 10 aged men, nocturia was due to a decrease of vasopressin secretion which resulted in a decrease of the solute free water reabsorption and an increase of diuresis. The obtained data are considered as an evidence for the role of renal autacoids, alongside with vasopressin, in regulation of the circadian rhythm of the kidney function.

Yellow fluorescent protein (3.6 ng) was administered through a catheter into the Wistar rat intestine lumen. By the method of confocal microscopy it has been established that as soon as in 3 min this protein appears in the epithelial cells of ileum, is absorbed into the blood and accumulated in cells of the nephron proximal segment, not being revealed in the liver, though. The protein accumulation in kidneys continues for several hours. The yellow fluorescent protein is homogeneously distributed in enterocytes, while in epithelial cells of the proximal tubule this protein is localized in vesicles. The data obtained indicate absorption of non-degraded yellow fluorescent protein in the intestine and role of kidney in metabolism not only of endogenous, but also of exogenous proteins.

The review summarizes data (more than 450 references) on concentration of human serum cations (Na+, K+, Ca2+, and Mg2+) and human blood serum osmolality depending on age, diverse physiological and pathological states, and action of physiologically active substances. There are summarized data of many thousand measurements of physicochemical parameters of the blood serum, the mean values of osmolality and cation concentrations in healthy people are calculated. The values are kept at a stable level throughtout the entire life since the moment of birth; in many cases they are maintained by regulatory systems within the normal limits and during various physiological and pathological states. There are formulated the main types of the states characterized by deviations from norm of physicochemical parameters of the internal medium fluids.