Effect of Hafnia alvei on Morphophysiologic Parameters and Gut Microbiota of Mice with Inherited Type 2 Diabetes Mellitus.

Inbred mouse strains KK.Cg-a/a and KK.Cg-Ay/a known as genetic models of type 2 diabetes mellitus significantly surpassed the control strain C57BL/6J in the body weight, relative weight of extractable fat, and basal blood glucose levels. Real-timePCR of fecal samples from KK.Cg-a/a and KK.Cg-Ay/a mice revealed dysbiosis typical of type 2 diabetes mellitus in humans and animals. Long-term intragastric administration of a suspension of Hafnia alvei bacteria had no effect on the above morphometric and biochemical parameters. At the same time, recovery of the Bacteroides spp. population in KK.Cg-Ay/a mice and a decrease in the number of Bifidobacterium spp. in KK.Cg-a/a mice were observed. The possibility of therapeutic use of the probiotic based on H. alvei is discussed.

Effect of TRPV1 on Activity of Isoforms of Constitutive Nitric Oxide Synthase during Regulation of Bicarbonate Secretion in the Stomach.

Application of mild irritants (1 M NaCl; pH 2.0) on the gastric mucosa potentiates the protective secretion of bicarbonates by epithelial cells. This response is mainly mediated by capsaicin-sensitive afferent nerve endings located in the submucosa. It was shown that activation of vanilloid type 1 receptors (TRPV1) induced by exogenous acidification of GM is not sufficient to potentiate the production of HCO3, including production depending on neuronal NO synthase. However, the effect of exogenous acid on TRPV1 leads to activation of endothelial NO synthase that restrict the gastric secretion of [Formula: see text].

Interaction of Constitutive Nitric Oxide Synthases with Cyclooxygenases in Regulation of Bicarbonate Secretion in the Gastric Mucosa.

Neuronal NO synthase blocker 7-nitroindazole suppressed bicarbonate secretion in rat gastric mucosa induced by mild local irritation with 1 M NaCl (pH 2.0). Non-selective blocker of neuronal and endothelial synthases, Nω-nitro-L-arginine (L-NNA), did not affect HCO3- production, but inhibited secretion after pretreatment with omeprazole. Non-selective cyclooxygenase blocker indomethacin inhibited HCO3- production under conditions of normal synthase activity and in the presence of L-NNA, but was ineffective when co-administered with 7-nitroindazole. It was concluded that neuronal and endothelial synthases are involved in different mechanisms of regulation of HCO3- secretion in the gastric mucosa induced by mild irritation. Activation of neuronal synthase stimulated HCO3- production, which is mediated mainly through activation of cyclooxygenase. Theoretically, activation of endothelial synthase should suppress HCO3- production. The effect of endothelial synthase depends on acid secretion in the stomach and bicarbonate concentration in the submucosa, as it was demonstrated in experiments with intravenous NaHCO3 infusion.

[EFFECT OF T1R3 RECEPTOR PROTEIN DELETION ON GLUCONEOGENESIS AND LIPID METABOLISM IN MICE].

Receptors of the T1R family are molecular sensors for sweet taste stimuli. They are expressed not only in the oral cavity, but in most of endocrine cells controlling homeostasis of glucose as well as in adipocytes. Earlier, we have demonstrated that deletion of the Taslr3 gene, which encodes the T1R3 protein, reduces glucose tolerance, elevates insulin resistance and cause a decrease of blood glucose level after food deprivation. The goal of the study was to elucidate an involvement of T1R3 in control of endogenous glucose synthesis and lipid metabolism. Experiments were performed with an inbred mouse strain C57BL/6ByJ and the Taslr3-gene knockout strain C57BL/6J-Tas1r3tm1Rfm maintained at the normocaloric diet. It was shown in vivo that the presence of intact T1R3 stimulates gluconeogenesis and lipid utilization during starvation and likely promotes glycogen synthesis. Additionally, T1R3 potentiates utilization of triglycerides and glycerol (in fed state) and restricts secretion of glucagon during fasting but does not affect insulin output. Thus, T1R3-mediated visceral reception of metabolites is involved in control of carbohydrate and lipid metabolism.

[ROLES OF CONSTITUTIVE SYNTHASES OF NITRIC OXIDE IN THE REGULATION OF GASTRIC BICARBONATE SECRETION INDUCED BY MILD IRRITATION OF THE MUCOSA].

Roles of isoforms of constitutive synthase of nitric oxide, neuronal or endothelial (nNOS or eNOS), in control of gastric bicarbonate secretion induced by mild irritation of the gastric mucosa was assessed at the normoacid state or after blockade of gastric acid secretion with omeprazole. In anesthetized rats, the concentration of HCO3- in luminal perfusate was calculated basing on measurements of pH/PCO2. Mucosal irritation during 20 min with acidic hypertonic solution (1 M NaCl, pH 2.0) caused marked and omeprazole-independent increase of HCO-secretion. Selective blocker ofnNOS in vivo 7-nitroindazole (7-NI), and the nonselective blocker ofnNOS and eNOS, N(G)-nitro-L-arginine (L-NNA), were applied either intravenously (10 mg/kg), or locally via retrograde injection into the splenic artery (1 mg/kg). At the normo-acid state, the irritation-induced secretion of was suppressed by 7-NI, but was not affected by L-NNA. After administration of omeprazole, both 7-NI and L-NNA equally inhibited HCO3- output. The effect of 7-NI (but not L-NNA) was abolished by cyclooxygenase (COX) inhibitor, indomethacin, which by itself suppressed irritation-induced secretion of HCO3-. Additionally, bicarbonate output was substantially reduced by the blocker of soluble guanylate cyclase (GC), methylene blue. We conclude that irritation-induced secretion of HCO3- is largely mediated by intramural nNOS and depends on GC-COX interaction. As it was theoretically estimated, eNOS activity caused a reduction of HCO3- output in the normo-acid stomach. Omeprazole abolished the effect of eNOS.

The Involvement of the T1R3 Receptor Protein in the Control of Glucose Metabolism in Mice at Different Levels of Glycemia.

The heterodimeric protein T1R2/T1R3 is a chemoreceptor mediating taste perception of sugars, several amino acids, and non-caloric sweeteners in humans and many other vertebrate species. The T1R2 and T1R3 proteins are expressed not only in the oral cavity, but also in the intestine, pancreas, liver, adipose tissue, and in structures of the central nervous system, which suggests their involvement in functions other than gustatory perception. In this study, we analyzed the role of the T1R3 protein in regulation of glucose metabolism in experiments with the gene-knockout mouse strain C57BL/6J-Tas1r3tm1Rfm (Tas1r3-/-), with a deletion of the Tas1r3 gene encoding T1R3, and the control strain C57BL/6ByJ with the intact gene. Glucose tolerance was measured in euglycemic or food-deprived mice after intraperitoneal or intragastric glucose administration. We have shown that in the Tas1r3-/- strain, in addition to the disappearance of taste preference for sucrose, glucose tolerance is also substantially reduced, and insulin resistance is observed. The effect of the Tas1r3 gene knockout on glucose utilization was more pronounced in the euglycemic state than after food deprivation. The baseline glucose level after food deprivation was lower in the Tas1r3-/- strain than in the control strain, which suggests that T1R3 is involved in regulation of endogenous glucose production. These data suggest that the T1R3-mediated glucoreception interacts with the KATP-dependent mechanisms of regulation of the glucose metabolism, and that the main role is likely played by T1R3 expressed in the pancreas and possibly in the central nervous system, but not in the intestinal mucosa, as it was suggested earlier.

[Involvement of Tas1r3 receptor protein in control of the metabolism of glucose at different levels of glycemia in mice].

The heterodimeric protein T1R2/T1R3 is a chemoreceptor mediating taste perception of sugars, several amino acids, and non-caloric sweeteners in humans and many other vertebrate species. The T1R2 and T1R3 proteins are expressed not only in the oral cavity, but also in the intestine, pancreas, liver, adipose, tissue, and in structures of the central nervous system, which suggests their involvement in functions other than gustatory perception. In this study, we analyzed the role of the T1R3 protein in regulation of glucose metabolism in experiments with the gene-knockout mouse strain C57BL6J-Tas1r3(tm1Rfm) (Tas1r3-/-), with a deletion of the Tas1r3 gene encoding T1R3, and the control strain C57BL/6ByJ with the intact gene. Glucose tolerance was measured in euglycemic or food-deprived mice after intraperitoneal to disappearance glucose administration. We have shown that in the Tas1r3-/- strain, in addition to disappearance of taste preference for sucrose, glucose tolerance is also substantially reduced, and insulin resistance is observed. The effect of the Tas1r3 gene knockout on glucose utilization was more pronounced in the euglycemic state than after food deprivation. The baseline glucose level after food deprivation was lower in the Tas1r3-/- strain than in the control strain, which suggested that the T1R3 is involved in regulation of endogenous glucose production. These data suggest that the T1R3-mediated glucoreception interacts with the K(ATP)-dependent mechanisms of regulation of the glucose metabolism, and that the main role is likely played by T1R3 expressed in the pancreas and possibly in the central nervous system, but not in the intestinal mucosa, as it was suggested earlier.

Effect of proton pump inhibitors on the secretion of bicarbonates and pepsinogen induced by chemical stimulation of the gastric mucosa.

Proton pump inhibitors were shown to affect the sensitivity of the gastric mucosa to chemical agents. This effect is associated with inhibition of proton back-diffusion and increase in the permeability of the gastric epithelium. We studied the effect of omeprazole on gastric secretion of bicarbonates and pepsinogen induced by irritation of the gastric mucosa in narcotized rats with a hypertonic solution of high acidity (500 mM NaCl, pH 2.0). Irritation of the gastric mucosa increased the basal secretion of bicarbonates and potentiated the secretion of HCO3(-)and pepsinogen induced by electrostimulation of the vagus nerve. Omeprazole stimulated the prostaglandin-induced increase in the basal secretion of HCO3(-)and pepsinogen. By contrast, bicarbonate production in response to vagal stimulation was suppressed in the presence of omeprazole. Our results indicate that proton pump blockade has a modulatory effect on gastric secretion of bicarbonates and pepsinogen induced by chemical stimulation of the gastric mucosa.

[Effect of mild irritants on gastric outputs of bicarbonates and pepsinogen depends on the rate of acid secretion].

The aggressive luminal content in the stomach activates gastroprotective processes affecting exocrine and endocrine secretion of gastric glands and permeability of the pre-epithelial mucus layer. The aim of the study was to investigate effects of chemical irritants similar to physiological characteristics of digestion (pH 2.0 and/or 500 mM NaCl) on outputs of bicarbonates and pepsinogen as well as assess the role of endogenous acid production in control ofnon-parietal secretion during irritation of the gastric mucosa. In experiments on conscious rats with chronic gastric fistula as well as on anesthetized animals it was demonstrated that luminal infusion of acidic hyperosmotic solution of NaCl enhances basal secretions of bicarbonates and pepsinogen that was fully blocked by indomethacin. Suppression of gastric acid secretion by omeprazole potentiates the stimulative effect of mild irritants likely due to the reduction of pH gradient on the surface of gastric mucosa which causes the growth of sensitivity of the epithelium to chemical stimuli and the increase of synthesis ofprostaglandins. Additionally, mild irritation enhances secretion of HCO3(-) and pepsinogen induced by stimulation of the vagus nerve; and this response does not depend on the action ofprostaglandins. The enhancing effect of irritation on the vagally induced bicarbonate output was eliminated after the treatment with omeprazole.

Selective regulation of acid, pepsinogen, and bicarbonate secretion in the stomach by different C-fiber populations of vagus nerve.

Acute experiments on anesthetized rats showed that group B nerve fibers of the subphrenic portion of the vagus nerve do not participate in the regulation of gastric secretion. Gastric acid production is mainly controlled by fast C-fibers (2.11 0.09 m/sec), while secretion of pepsinogen and bicarbonates depends on activity of both fast and slow (0.95 0.11 m/sec) C-fibers. Some fast conduction C-fibers stimulating the release of bicarbonates in the stomach are capsaicin-sensitive afferents. The local effect of these afferents depends on cholinergic transmission and most probably it is mediated via its modulation.

[The role of histamine in vagal and gastrin effects on the secretory function of the rat stomach]. / Rol' gistaminovogo zvena v mekhanizmakh vagusnykh i gastrinovykh vliianii na sekretornuiu funktsiiu zheludka krys.

In lumen-perfused stomachs of anaesthetized rat, acid and bicarbonate types of secretion were estimated on the basis of pH/PCO2 measurements. The data obtained reveal that, in anaesthetised rats, pentagastrin and cholinergic input affect acid secretion mainly indirectly via histamine release. Vagal effects on pepsinogen output are mediated partially via indirect histamine pathways. The direct action of pentagastrin, however, predominates. Bicarbonate production is subjected to cholinergic control alone.

[The neuronal impulse activity of the subepicardial plexus in the isolated heart of the cat]. / Impul'snaia aktivnost' neironov subépikardial'nogo spleteniia v izolirovannom serdtse koshki.

The unit activity recorded in the right atrium plexus of the Langendorff preparation was spontaneously irregular in 20 per cent of the neurons. Hexamethonium abolishes it. The spontaneous activity and vagus-induced discharges were inhibited by adrenaline or by stimulation of the stellate ganglion in nearly 30 per cent of the neurons. Activity of some spontaneously active units depended on the effect of the experimental procedure.

[The age-related characteristics of changes in osmotic and ionic homeostasis in spontaneously hypertensive rats]. / Vozrastnye osobennosti izmenenii osmoticheskogo i ionnogo gomeostaza u spontanno-gipertenzivnykh krys.

The 3-month old SHR differ from the WKY rats in that the former have an increased osmolality, concentration of albumins, activity (but not the concentration) of sodium and a reduced activity of potassium. The shifts in the albumins concentration occur, mainly, on account of the amino acid phenylalanine. The gradient increase of the sodium and potassium concentration between the plasma and muscular tissue in followed by a slight hyperpolarisation of the muscle fibers, a drop in the lability and a increase in pO2. The above shifts of homeostatic parameters were not revealed in the SHR and WKY rats of 1.5 and 6.0 months of age.

[Comparative effectiveness of intracoronary and systemic thrombolytic therapy of acute myocardial infarction]. / Sravnite'lnaia otsenka éffektivnosti intrakoronarnoi i sistemnoi tromboliticheskoi terapii ostrogo infarkta miokarda.

Systemic thrombolytic therapy with streptodekase was shown to produce the same effects as intracoronary thrombolytic therapy with avelysine. The blood flow in the coronary vessels could be restored in 72.7% with intracoronary therapy and in 66.7% with systemic thrombolytic therapy. Death rates were 9.1 and 8.9%, respectively, and in 3.1 and 3.3% with reperfusion. A difference was found in the frequency of myocardial infarction-associated complications, depending on the modality of thrombolytic therapy. In the authors' opinion, in clinical institutions where operations on coronary vessels are not supposed to be made after thrombolytic therapy, the systemic thrombolytic therapy with streptodekase should be preferred as it is simplier, safer and easier to apply.