Hypertonic NaCl Solution Research Articles

Condensed tannin accretions specifically distributed in mesophyll cells of non-salt secretor mangroves help in salt tolerance.

Auto-fluorescent condensed tannins specifically accumulated in mesophyll cells of non-salt secretor mangroves are involved in the compartmentation of Na+ and osmotic regulation, contributing to their salt tolerance. Salinity is a major abiotic stress affecting the distribution and growth of mangrove plants.The salt exclusion mechanism from salt secretor mangrove leaves is quite known; however, salt management strategies in non-salt secretor leaves remain unclear. In this study, we reported the auto-fluorescent inclusions (AFIs) specifically accumulated in mesophyll cells (MCs) of four non-salt secretor mangroves but absent in three salt secretors. The AFIs increased with the leaf development under natural condition, and applied NaCl concentrations applied in the lab. The AFIs in MCs were isolated and identified as condensed tannin accretions (CTAs) using the dye dimethyl-amino-cinnamaldehyde (DMACA), specific for condensed tannin (CT), both in situ leaf cross sections and in the purified AFIs. Fluorescence microscopy and transmission electron microscope (TEM) analysis indicated that the CTAs originated from the inflated chloroplasts. The CTAs had an obviousmembrane and could induce changes in shape and fluorescence intensity in hypotonic and hypertonic NaCl solutions, suggesting CTAs might have osmotic regulation ability and play an important role in the osmotic regulation in MCs. The purified CTAs were labeled by the fluorescent sodium-binding benzofuran isophthalate acetoxymethyl ester (SBFI-AM), confirming they were involved in the compartmentation of excess Na+ in MCs. This study provided a new view on the salt resistance-associated strategies in mangroves.

Влияние изменений водно-солевого баланса на ионо- и осморегулирующую функции почек у озерной лягушки

Changes in the water-salt balance and excretion of ions by the kidney after subcutaneous injections of hypertonic and isotonic NaCl solutions and dehydration were analyzed in lake frogs (Pelophylax ridibundus). The introduction of 0,75 M NaCl and dehydration for 1 hour increased the serum osmolality and Na+ and Cl– concentrations, and injections of isotonic solution did not affect these parameters. The applied treatments increased the level of Na+ and Cl– in the urine, and renal excretion of these ions. The most pronounced changes, including an increase in diuresis and glomerular filtration rate, were found after 0,75 М NaCl injection. In renal proximal tubules, changes in the pattern of the chloride channel (ClC-5), presumably involved in the process of protein endocytosis, were detected. An increase in the number of ClC-5-immunopositive tubule profiles and the intensity of the fluorescent signal in the apical cytoplasm of epithelial cells were revealed by immunohistochemistry and confocal microscopy. Studied effects of hypernatremia, hypervolemia and dehydration may be useful for further investigations of kidney function and mechanisms of epithelial tubular transport in frog models.

BRONCHIECTASIS IN ADULT PATIENTS: CLINICAL PECULIARITIES AND APPROACHES TO THE TREATMENT.

The aim: To perform a clinical analysis of bronchiectasis in adults, to analyze the effectiveness of nebulizer therapy with hypertonic NaCl solution with hyaluronic acid. Materials and methods: All patients were performed clinical-functional examination (MRC dyspnea index, Sp O2, 6-minute walking test, external respiration function); calculated the index BODE, analyzed the SGRQ, studied the results of sputum. Statistical data analysis was performed using the Microsoft Excel for Microsoft 365 MSO 16.0.13530.2040418 package of statistical functions. Results: The main symptom in 100% of cases was chronic cough with production of sputum. Patients were concerned about shortness of breath (91.7%), episodic hemoptysis (29.2%), systemic symptoms (fatigue, weight loss). Hypertonic NaCl solution has a direct mucolytic effect, osmotic and anti-edematous effect. Protection of the mucous membrane of the respiratory tract makes hyaluronic acid an ideal additional component of hypertonic saline solution. All patients showed a positive effect of treatment immediately. After 2 weeks, the respiratory rate decreased, the FEV1 index increased at 8.6 (p<0.05), SpO2 increased up to 93.75 ± 7.13%, the number of points according to the SGRQ decreased, BODE index also decreased. Conclusions: Leading clinical signs of bronchiectasis were: a chronic cough with daily sputum production (100% of patients), shortness of breath (91.7%). The use of nebulizer inhalations decreased shortness of breath at 17.6% (р<0.05), improved external respiratory function indices (FVCL increased at 9.7% (р<0.01), FEV1 at 8.6% (р<0.01)) and blood oxygen saturation increased at 4.9% (р<0.05)). The offered complex increased tolerance to physical exertion (the 6-minute walk test and 4-year survival (BODE prognostic index).

S-51-6: RENOVASCULAR HYPERTENSION AND BRAIN: ROLE OF THE RENIN-ANGIOTENSIN SYSTEM AND SODIUM

Renovascular hypertension is a type of secondary hypertension. Renovascular hypertensive 2-kidney, 1-clip (2K1C) rats have an increased activity of the renin-angiotensin system, and it is an experimental model to study renovascular hypertension. Renovascular hypertensive 2K1C rats have an imbalance of RAS components in the brain, an impairment of the baroreflex and they present an increase in daily intake of hypertonic NaCl solution. Therefore, we focused on studying: 1) the effects of overexpression of RAS components in the in the nucleus of the solitary tract (NTS), a brainstem area involved with cardiovascular control, 2) the brain mechanisms involved with the sodium appetite (operationally defined as an ingestion of hypertonic NaCl solution) in 2K1C rats. In adult Holtzman rats, the left renal artery was partially occluded by a silver clip with an opening of 0.2 mm to induce 2K1C. The experiments started after 6 weeks (hypertension plateau). We observed that increasing angiotensin type 2 receptor (AT2R) expression in the NTS attenuated the development of renovascular hypertension and also reversed the impairment of the baroreflex observed in 2K1C rats. Furthermore, an observed decrease in mRNA levels of angiotensin-converting enzyme 2 in the NTS of 2K1C rats was restored to control levels after viral-mediated increases in AT2R at this site. Virally mediated blockade of an intracellular pathway activated by angiotensin II (ANG II) acting in type 1 receptor (AT1R) in the NTS attenuated the development of renovascular hypertension and also reversed the impairment of the baroreflex. Daily 0.3 M NaCl intake transiently increased from the 2nd to the 5th week after 2K1C surgery. On the 6th week, in spite of comparable daily 0.3 M NaCl intake between 2K1C and sham rats, water deprivation (used to induce sodium appetite) produced a greater increase 0.3 M NaCl intake in 2K1C rats. Moreover, this intake is totally blocked by central AT1R and mineralocorticoid receptor antagonism. These data demonstrated that ANG II acting in the AT1R in the NTS is involved with the development of hypertension and baroreflex impairment in 2K1C and that AT2 overexpression at the same site can counteract these effects. In addition, the results demonstrated the participation of ANG II and aldosterone acting centrally in the enhanced sodium intake in water deprived 2K1C rats.

Ефективність і безпечність застосування інгаляцій 6% N-ацетилцистеїну в 3% розчині NaCl у клінічній практиці (огляд літератури)

The article summarizes the literature on the use of N-acetylcysteine and its combination with 3% NaCl solution (FLU-ACYL broncho) in clinical practice. Studies show that N-acetylcysteine is currently effective in the treatment of respiratory diseases due to its multicomponent effects on the respiratory system and the immune system. Hypertonic (3%) NaCl solution potentiates the action of N-acetylcysteine by inhalation and allows to achieve good results in the treatment of acute and chronic respiratory diseases in the optimal time. One of the well-known in Ukraine products for fast and effective evacuation of viscous sputum is FLU-ACIL broncho, sterile solution for nebulizer and instillation. One 5 ml ampoule contains 300 mg of NAC, which has a mucolytic effect in direct contact with mucus, and 150 mg of hypertonic NaCl solution, which draws water from the intracellular space into the extracellular space by osmosis and increases the proportion of water in the bronchial secretion, dilutes it and thus facilitates its removal. The combination of NAC with hypertonic NaCl solution creates synergy and allows to obtain optimal treatment results with minimal side effects. This combination has mucolytic, anti-film, antiviral, antioxidant, anti-inflammatory and immunomodulatory effects, making it promising in a pandemic SARS-CoV-2. No conflict of interests was declared by the authors.

Diagnostic and therapeutic approach to hypernatremia.

Hypernatremia occurs when the plasma sodium concentration is greater than 145mmol/L. Depending on the duration, hypernatremia can be differentiated into acute and chronic. According to severity: mild, moderate and threatening hypernatremia. Finally, depending on pathogenesis, hypernatremia can be defined as hypervolemic, hypovolemic, and euvolemic. Acute hypervolemic hypernatremia is often secondary to increased sodium intake (hypertonic NaCl and NaHCO3 solutions). Instead, chronic hypervolemic hypernatremia may be an expression of primary hyperaldosteronism. Euvolemic hypernatremia occurs in diabetes insipidus: depending on the underlying pathogenesis, it can be classified into two basic types: neurogenic (or central) and nephrogenic. The neurogenic form may be triggered by traumatic, vascular or infectious events; the nephrogenic form may be due to pharmacological causes, such as lithium, or non-pharmacological ones, such as hypokalemia. For hypovolemic hypernatremia, possible explanations are renal or extrarenal losses. The main goal of treatment of hypernatremia is the restoration of plasma tonicity. In particular, if the imbalance has occurred acutely, rapid correction improves the prognosis by preventing the effects of cellular dehydration; if hypernatremia has developed slowly, over a period of days, a slow correction rate (no more than 0.4mmol/L/h) is recommended.

Hypertonic Solution in Severe COVID-19 Patient: A Potential Adjuvant Therapy.

Coronavirus disease 2019 (COVID-19) features hyper-inflammation, cytokine storm, neutrophil function changes, and sodium chloride (NaCl) homeostasis disruption, while the treatment with NaCl hypertonic solutions (HS) controls electrolytic body homeostasis and cell functions. HS treatment is a simple, popular, economic, and feasible therapy to regulate leukocyte function with a robust anti-inflammatory effect in many inflammatory diseases. The purpose of this narrative review is to highlight the knowledge on the use of HS approaches against viral infection over the past years and to describe the mechanisms involved in the release of neutrophil extracellular traps (NETs) and production of cytokine in severe lung diseases, such as COVID-19. We reported the consequences of hyponatremia in COVID-19 patients, and the immunomodulatory effects of HS, either in vitro or in vivo. We also described the relationship between electrolyte disturbances and COVID-19 infection. Although there is still a lack of clinical trials, hypertonic NaCl solutions have marked effects on neutrophil function and NETs formation, emerging as a promising adjuvant therapy in COVID-19.

Randomised comparative study on the efficacy of 3% versus 30% NaCl solution in the treatment of umbilical granuloma.

This study aimed to compare the efficacy of 3% versus 30% NaCl solution in treating umbilical granuloma (UG) and to evaluate parental satisfaction. A randomised, double-blinded, comparative study in neonates with UG was conducted. Stratified, block-of-four randomisation was used to allocate neonates into two groups, treated with 3% or 30% pharmaceutical-grade NaCl solution, three times daily. The time to resolution was determined by daily photographs of UG and weekly hospital visits. If there was no response after 2 weeks, silver nitrate was used. Parental satisfaction was measured on a rating scale of 1-5. One hundred neonates were enrolled, 48 in the 3% NaCl group and 52 in the 30% NaCl group. Baseline demographic data were not different between the groups. There was no significant difference in the resolution rate (93.8% vs 98.1%) or the median (interquartile range) time to resolution (7 (5-13) vs 7 (4-11) days) between the 3% and 30% NaCl groups, respectively. No skin burn or cellulitis was detected. About 95% of parents scored >4 for satisfaction. Hypertonic NaCl solution is highly effective in treating UG without side effects. Hypertonic NaCl solution should be considered as an alternative treatment for UG.

Evaluation of the efficacy and safety of the 7% hypertonic solution with hyaluronic acid in patients with COVID-19 in the outpatient phase

Introduction. Since 2020, the pandemic caused by the SARS-CoV-2 virus poses a serious threat to health systems in many countries around the world. Finding inexpensive and affordable, effective and safe medications that can promote rapid recovery and reduce the risk of a severe course of COVID-19 is an important challenge for the health care system of any country. It has long been known that 7% hypertonic sodium chloride solution has nonspecific antiviral, antibacterial and antifungal properties. A 2020 study shows the effectiveness of hypertonic NaCl solutions in blocking SARS-CoV-2 replication in Vero cells. These data suggest that hypertonic solutions can be used as a prophylactic and alternative comprehensive treatment for patients with COVID-19.Aim. We study the efficacy and safety of hypertonic solution with hyaluronic acid in patients undergoing outpatient treatment with mild to moderate COVID-19.Materials and methods. We conducted an open prospective study of the use of hyaluronic acid (HA) solution 7% (Ingasalin® forte 7%) in outpatients with confirmed SARS-CoV-2 infection who had 1 or more risk factors for a severe course of the disease. Patients were divided into 2 groups of 30 patients each. The main group received, in addition to standard therapy (according to the interim guidelines in effect at the time of treatment, version 14 dated 12/27/21), inhalation of 7% HG with HA in the morning and evening for 10 days; patients in the control group received standard therapy according to the interim guidelines.Results and discussion. Patients of the study group who received hyaluronic acid solution 7% had statistically significant decrease of dyspnea and normalization of saturation values already on the 5th day of therapy compared to patients of the control group. One patient in the study group was hospitalized, and 4 patients in the control group were hospitalized. There were no side effects associated with the administration of hyaluronic acid solution 7%. Also, there was no development of cough or its intensification against the background of inhalation in patients of the main group.Conclusion. It is reasonable to use hyaluronic acid solution 7% in outpatients with mild to moderate COVID-19 and with one or more risk factors of severe disease course as part of complex therapy.

Липосомальная форма дексаметазона в коррекции экспериментального острого повреждения легких

Objective. To investigate the possibility of pharmacological correction of acute lung injury of aspiration genesis with a liposomal form of dexamethasone in experiment. Materials and methods. For the experiment, simple liposomes were prepared from phosphatidylcholine and cholesterol with an average size of 320±50 nm and a dexamethasone concentration of 2.98±0.02 mg/ml. The study used outbred white rats, divided into four groups of 16 animals. 1st group Control (without experimental therapy), 2nd group - Experiment 1, where a solution of dexamethasone was injected intravenously at a dose of 6 mg/kg, 3rd group - Experiment 2, where an intravenous combination of dexamethasone solution (6 mg/kg) and hypertonic (7.5%) NaCl solution was administered once, and group 4 - Experiment 3, where liposomes with dexamethasone (6 mg/kg) were injected intravenously once in hypertensive (7.5%) NaCl solution. The main functional parameters of the animals (heart rate, blood pressure, saturation of hemoglobin with oxygen, partial pressure of blood oxygen and respiration rate) were subject to analysis. Functional parameters were analyzed before modeling acute lung injury and after 5 min, 1, 4, 24 hours, and 6 days. At the end of the experiment (day 6) the degree of pulmonary edema and histological signs of acute lung injury were assessed. Morphology was assessed quantitatively in each group. Results. The study found that liposomal dexamethasone in hypertonic NaCl solution, when administered intravenously, was more effective than aqueous dexamethasone solution in correcting functional impairment in acute lung injury. The combination of hypertonic sodium chloride solution with dexamethasone more markedly increases blood pressure and reduces the degree of pulmonary oedema. In acidine pepsin aspiration, liposomal dexamethasone in hypertonic NaCl solution most effectively increased animal survival. Conclusion. Compared with dexamethasone in hypertonic NaCl solution, liposomal dexamethasone is more effective in increasing animal survival and protecting lung tissue from aspiration damage by acidine pepsin.

Роль етапу дегідратації в розвитку постгіпертонічного гемолізу еритроцитів ссавців

The aim of this study was to assess the level of damage to mammalian erythrocytes under post-hypertonic shock depending on the concentration of NaCl in the dehydration medium and to determine the effect of hypertonic NaCl solutions on the condition of mammalian erythrocytes by flow cytometry. To achieve this goal, spectrophotometric and cytometry research methods were used. The data obtained showed that post-hypertonic lysis of mammalian erythrocytes depends on the concentration of NaCl in the dehydration medium. The most sensitive to the effects of post-hypertonic shock are rat erythrocytes, the least sensitive are rabbit cells. Cytometry studies revealed significant changes in the histograms of the distribution of erythrocytes of all mammalian species with increasing salt concentration in the dehydration medium. These changes are species-specific and are probably related to changes in cell volume and morphology. The data revealed a relationship between the level of post-hypertonic hemolysis and the values of such indicators as the median distribution and the coefficient of variation. Thus, an increase in the sensitivity of mammalian erythrocytes to post-hypertonic shock with increasing salt concentration in dehydration medium was usually accompanied by a decrease in the median cell division, and higher values of the coefficient of variation are characteristic of mammalian erythrocytes resistant to post-hypertonic shock.

Bronchial granulocytes in the development of epithelial destruction and oxidative lipid modification in patients with bronchial asthma with cold and osmotic airway hyperresponsiveness

Free radical damage to the respiratory tract in patients with asthma leads to the destruction of the bronchial parenchyma and the generation of signaling molecules of inflammation by parenchymal cells. Objective: to study the role of the structural and functional status of granulocytes in the development of epithelial destruction and oxidative lipid modification in the bronchi of asthma patients with airway hyperresponsiveness to cold and hyperosmolar stimuli. Material and methods. In 48 asthma patients, the level of asthma control was assessed according to the Asthma Control Test (ACT) questionnaire; lung function; bronchial response to 3-minute isocapnic hyperventilation with cold (- 20 °C) air (IHCA) and with ultrasonic inhalation of hypertonic (4.5 %) NaCl solution (IHS). The cellular composition and the degree of cellular destruction in induced sputum (IS) were measured. Reaction products for enzymes from the group of heme-containing peroxidases (myeloperoxidase in neutrophils, peroxidase in eosinophils) with the calculation of the average cytochemical coefficient were studied. The content of lipid peroxidation products in according to ultraviolet absorption spectra of lipid extracts in exhaled breath condensate (EBC) was assessed. Results. Patients of group 1 (n=15) with airway hyperresponsiveness to IHCA and IHS in relation to group 2 (n=33) with a negative reaction had lower ACT (14.7±1.4 vs. 18.4±0.8 points, p=0.017). In sputum, the number of neutrophils in groups 1 and 2 was 41.8±6.4 vs. 33.6±3.4 %, eosinophils – 23.5±3.5 vs. 14.9±2.6 %; average cytochemical coefficient of peroxidase 117.5±12.5 vs. 88.8±8.9 pixels (p=0.07), cell destruction index (CDI) of bronchial epithelium 0.56±0.04 vs. 0.39±0.02 r.u. (p =0.0002). The content of diene conjugates (E233) in EBC in group 1 was higher than in group 2 (0.07±0.008 vs. 0.05±0.005 optical units, p˂0.05). A correlation was found between peroxidase level and CDI, the number of totally destroyed cells (IV class of cell destruction), between the number of neutrophils in IS and E233, as well as the ratio of E233 to E206 (non-oxidized lipids) in EBC. Conclusion. In asthma patients with airway hyperresponsiveness to cold and hyperosmolar stimuli, changes in the structure of the epithelium and the structural and functional profile of granulocytes are associated with the activation of the peroxidase function of granulocytes and are interrelated with lipid peroxidation.

Obstetric blood loss: priorities in the choice of infusion solutions

Background. Bleeding accounts for 34 % of maternal mortality. Every 7 minutes 1 woman dies from bleeding during the labour. Retrospective analysis of medical records shows that in 60-80 % of cases, fatal consequences can be avoided. Criteria for defining the concept of “massive blood loss” are the loss of 100 % of circulating blood volume (CBV) within 24 hours or 50 % of CBV within 3 hours, loss of 150 ml/min, of 2 % of body weight within 3 hours, reduction of hematocrit by 10 % in combination with hemodynamic disturbances, one-time blood loss more than 1500-2000 ml or 25-35 % CBV, the need for transfusion of &gt;10 doses of erythromass for 24 hours. The main causes of bleeding in obstetrics include uterine atony, premature placental abruption, uterine rupture, placental abruption, hereditary blood diseases, coagulopathy, sepsis, amniotic fluid embolism.&#x0D; Objective. To describe infusion therapy (IT) for obstetric bleeding.&#x0D; Materials and methods. Analysis of literature data on this issue.&#x0D; Results and discussion. Strategies for the treatment of obstetric hemorrhage include restriction of the traditional massive crystalloid-based IT, applying the principle of antihypertensive resuscitation, using of adequate doses of tranexamic acid, fibrinogen concentrate and prothrombin complex concentrate, early informed use of blood components, and low-volume IT. Routine use of unbalanced crystalloid solutions in critically severe patients is dangerous. Infusion of large amounts of 0.9 % NaCl may cause metabolic hyperchloremic acidosis. Therefore, except in cases of hypochloremia, it is advisable to replace saline with balanced solutions. Reosorbilact (“Yuria-Pharm”) is the most suitable solution for this purpose. It mobilizes the own fluid of the organism, helping it to move from the intercellular space into the vessels. Hypotensive resuscitation involves the introduction of limited amounts of fluid in the early stages of treatment of hemorrhagic shock (until the bleeding stops). Low-volume IT program is a part of hypotensive resuscitation. In this case, the following solutions can be used: Reosorbilact, Sorbilact, Gekoton (“Yuria-Pharm”), 130/0.4 hydroxyethyl starch (HES), hypertonic NaCl solutions (including combined solutions with colloids), polyhydric alcohols. It should be noted that the new generation of HEC has less effect on coagulation than older drugs. Due to the risk of kidney damage, HEC solutions should be used in the lowest effective dose for as shortest period of time as possible. HEC infusion should be stopped as soon as hemodynamic targets are reached. Solutions containing polyhydric alcohols (Reosorbilact, Sorbilact, Xylate) occupy an important position in IT of critically ill patients. Due to their high osmolarity, Reosorbilact and Sorbilact cause fluid to move from the intercellular space into the vascular bed, improving microcirculation and tissue perfusion. The polyhydric alcohol sorbitol contained in these solutions creates increased osmotic pressure in the renal tubules, which provides a diuretic effect. In case of the blood loss volume of I-II functional class up to 1500 ml and stopped bleeding, IT is performed in a limited mode. The volume of intravenous infusion together with blood components should not exceed 200 % of the blood loss volume. Reosorbilact (10-15 ml/kg) is an initial solution in combination with 0.9 % NaCl (20-30 ml/kg). In case of unstable hemodynamics HEC may be added (up to 1,5 L). Blood components are used only in case of confirmed coagulopathy and continued bleeding. In case of massive critical blood loss &gt;1500-2000 ml, it is advisable to use the protocol of massive blood transfusion 1:1:1:1. In order to reduce the pathological response of the endothelium to IT, it is advisable to use a substrate for the nitric oxide synthesis, namely, Tivortin (“Yuria-Pharm”). To stop life-threatening obstetric bleeding, CBV must be refilled using the protocol of massive blood transfusion and automatic blood reinfusion, oxytocin and prostaglandin analogues for the correction of uterine tone, uterine massage, correction of coagulopathy, balloon tamponade of the uterus.&#x0D; Conclusions. 1. Emergency care for massive bleeding in obstetrics is one of the priorities in reducing maternal morbidity and mortality. 2. Intensive therapy of blood loss should be based on modern recommendations and the use of modern drugs. 3. The indications for transfusion of blood components should be clearly applied.

Complex Method of CT and Morphological Examination of Placental Angioarchitechtonics.

We propose an original method of complex assessment of the placental angioarchitechtonics based on computed tomography (CT) and morphological examination. A prerequisite condition of successful examination and assessment of the placental angioarchitechtonics is the pre-preparative stage including clearing of the placental and umbilical cord vessels from blood clots by placement of placenta into 10% hypertonic NaCl solution and then on a hygroscopic substrate. The major stage of this method is injection of contrast staining mixtures into the umbilical vessels followed by CT. The concentration of radiocontrast agent in water solution of gouache should be 70% for arteries and 15% for veins. The volumes of mixtures for contrast staining should be calculated according to the weight of the placenta. The contrast staining mixture was first injected into the catheterized unpaired umbilical vein, and then into both umbilical arteries. Each injection of the contrast staining mixture was visually inspected; then branching of the stained vessel was photographed and scanned by CT. The CT scans were used to construct 3D models of placental vessels and spectral color maps, which made it possible to examine the peculiarities of placental angioarchitechtonics, to identify and evaluate anastomoses of placental vessels, and to establish the type of these anastomoses.

SLC9A4 in the organum vasculosum of the lamina terminalis is a [Na+] sensor for the control of water intake.

Nax is a brain [Na+] sensor expressed in the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT) in the brain. We previously demonstrated that Nax signals are involved in the control of water intake behavior through the Nax/TRPV4 pathway. Nax gene knockout mice showed significantly attenuated water intake after an intracerebroventricular (ICV) injection of a hypertonic NaCl solution; however, the induction of a certain amount of water intake still remained, suggesting that another unknown [Na+]-dependent pathway besides the Nax/TRPV4 pathway contributes to water intake. In the present study, we screened for novel [Na+] sensors involved in water intake control and identified SLC9A4 (also called sodium (Na+)/hydrogen (H+) exchanger 4 (NHE4)). SLC9A4 is expressed in angiotensin II (Ang II) receptor type 1a (AT1a)-positive neurons in the OVLT. Sodium-imaging experiments using cultured cells transfected with slc9a4 revealed that SLC9A4 was activated by increases in extracellular [Na+] ([Na+]o), but not osmolality. Moreover, the firing activity of SLC9A4-positive neurons was enhanced by increases in [Na+]o and Ang II. slc9a4 knockdown in the OVLT reduced water intake induced by increases in [Na+], but not osmolality, in the cerebrospinal fluid. ICV injection experiments of a specific inhibitor suggested that the increase in extracellular [H+] caused by SLC9A4 activation next stimulates acid-sensing channel 1a (AS1C1a) to induce water intake. Our results thus indicate that SLC9A4 in the OVLT functions as a [Na+] sensor for the control of water intake and that the SLC9A4 signal is independent of the Nax/TRPV4 pathway.

Effective diffusion coefficients and mass flux ratio during osmotic dehydration considering real shape and shrinkage

The aim of this work was to solve a model regarding water loss and soluble solids gain during osmotic dehydration (OD), considering real shape and solid shrinkage along the process. As an experimental case of study, OD of tomatoes halves of semi-ellipsoidal shape in hypertonic solutions of sucrose and NaCl, was selected. OD assays were carried out in two hypertonic solutions (soluble solids 35% and 50% (w/w)) with 1:8 (w/w) tomato/solution at 25 °C. Comsol Multiphysics coupled with Matlab computational tools were used for solving model's equations applying finite elements method and optimization algorithms for parameter estimation. Effective diffusion coefficients and water to soluble solids total mass flux ratios were determined. Diffusion coefficients resulted smaller than those for a rigid solid and are independent of the solids geometry and contraction. Water to soluble solids flux ratio was bigger than 1 and increased with the osmotic solution concentration and solid shrinkage.

Влияние ингибитора дипептидилпептидазы-4 на выведение ионов натрия и воды почками у крыс при изменениях водно-солевого баланса

Желудочно-кишечный тракт секретирует широкий спектр пептидов, регулирующих метаболические процессы и влияющих на функции почек и водно-солевой баланс. Эффекты данных биологически активных веществ можно усилить увеличением их периода полужизни путем угнетения фермента дипептидилпептидазы-4. Цель исследования - изучение экскреции ионов натрия и воды при угнетении дипептидилпептидазы-4 вилдаглиптином у крыс с различным состоянием водно-солевого баланса. Методика. Состояния гипернатриемии, гиперосмии или гипоосмии моделировали пероральным введением гипертонического и изотонического растворов NaCl и воды. Результаты. Вилдаглиптин вызвал дозозависимое снижение активности фермента дипептидилпептидазы-4 с максимумом эффекта при дозе 1 мг на 100 г массы тела. Его введение перед гипертонической натриевой нагрузкой увеличивало экскрецию натрия на 56%, усилило реабсорбцию осмотически свободной и свободной от натрия воды. Введение ингибитора дипептидилпептидазы-4 перед изотонической натриевой нагрузкой усиливало экскрецию натрия в той же степени, но не влияло на реабсорбцию воды. Инъекция вилдаглиптина, предваряющая водную нагрузку, вызвала антидиуретическую реакцию почек. Заключение. Блокада дипептидилпептидазы-4 вилдаглиптином способствует выведению из организма избыточного количества натрия и изменению реабсорбции воды в зависимости от концентрации ионов натрия в сыворотке крови, вероятно, за счет увеличения периода циркуляции кишечных регуляторных пептидов, секретирующихся в ответ на пероральные нагрузочные пробы NaCl. Данные процессы ускоряют восстановление водно-солевого гомеостаза в условиях поступления избытка натрия через желудочно-кишечный тракт. The gastrointestinal tract secretes multiple peptides that regulate metabolic processes and influence the kidney function and water-salt balance. The effects of these biologically active substances can be intensified by increasing their half-life through inhibition of the dipeptidyl peptidase-4 (DPP-4) enzyme. The aim of the study was investigation of sodium and water excretion after inhibition of DPP-4 with vildagliptin in rats with different states of the water-salt balance. Methods. The hypernatremic, hyperosmotic and hypoosmotic states were modeled by oral administration of hypertonic and isotonic NaCl solutions or water. Results. Vildagliptin induced a dose-dependent decrease in the DPP-4 activity with a maximum effect of 1 mg per 100 g of body weight. Vildagliptin administration prior to the hypertonic sodium load increased sodium excretion by 56% and stimulated reabsorption of solute-free and sodium-free water. Administration of the DPP-4 inhibitor before the isotonic sodium load increased sodium excretion to the same degree without affecting the water reabsorption. A vildagliptin injection prior to the water load resulted in an antidiuretic response of the kidneys. Conclusion. The inhibition of DPP-4 activity with vildagliptin promoted removal of excessive sodium from the body and changed the water reabsorption depending on the sodium concentration in the blood serum, presumably by prolonging circulation of the intestinal regulatory peptides secreted in response to oral NaCl load tests. These processes accelerate restoration of the water-salt homeostasis in the conditions of excessive sodium delivery through the gastrointestinal tract.

Ионорегулирующая функция почек и эффект глюкагоноподобного пептида-1 у крыс на высокосолевой диете

Glucagon-like peptide-1 (GLP-1) is the main incretin hormone that has an insulinotropic effect after a meal, as well as a physiologically significant natriuretic factor that contributes to the regulation of sodium and water balance. The aim of the work is to evaluate the effect of GLP-1 and its mimetic on the ion-regulating function of the kidneys in rats that are kept on a diet with a high concentration of NaCl for a long time, as well as in experimental hypervolemia and hypernatremia. In Wistar rats that received feed with a high content of NaCl (4%) for a month compared to animals on a standard diet (0.4% NaCl) the levels of blood pressure and atrial natriuretic peptide did not change, the aldosterone concentration in the blood decreased, the urinary excretion of sodium, calcium and chloride ions increased. After the administration of glucagon-like peptide-1 (GLP-1) and its mimetic, exenatide, the excretion of sodium ions and chlorides by the kidneys increased, the magnitude of natriuresis was equal in rats with different levels of NaCl intake with feed, that indicates the independence of the natriuretic action of GLP-1 from the excess of NaCl in the body due to the long-term high salt intake. In contrast to the standard diet, on high-salt feed, a lower level of aldosterone in the blood of rats caused a lower loss of potassium in the urine under the action of GLP-1 and exenatide. Similar changes in the urinary sodium and potassium excretion were observed under the action of GLP-1 mimetic in rats with hypervolemia caused by intraperitoneal administration of isotonic NaCl solution. A summation of the effects of exenatide and a loading test on the excretion of sodium was observed in rats with hypernatremia after administration of hypertonic solution of NaCl. Thus, GLP-1 is an effective natriuretic factor, both under standard conditions of water-salt balance, as well as with acute and chronic excess of NaCl in the body.

Na+] Increases in Body Fluids Sensed by Central Nax Induce Sympathetically Mediated Blood Pressure Elevations via H+-Dependent Activation of ASIC1a

Increases in sodium concentrations ([Na+]) in body fluids elevate blood pressure (BP) by enhancing sympathetic nerve activity (SNA). However, the mechanisms by which information on increased [Na+] is translated to SNA have not yet been elucidated. We herein reveal that sympathetic activation leading to BP increases is not induced by mandatory high salt intakes or the intraperitoneal/intracerebroventricular infusions of hypertonic NaCl solutions in Nax-knockout mice in contrast to wild-type mice. We identify Nax channels expressed in specific glial cells in the organum vasculosum lamina terminalis (OVLT) as the sensors detecting increases in [Na+] in body fluids and show that OVLT neurons projecting to the paraventricular nucleus (PVN) are activated via acid-sensing ion channel 1a (ASIC1a) by H+ ions exported from Nax-positive glial cells. The present results provide an insight into the neurogenic mechanisms responsible for salt-induced BP elevations.

Dose-dependent mortality involving convulsions due to subarachnoid Urografin® injection in rats.

An ionically hypertonic contrast medium Urografin® was inadvertently administered into the subarachnoid space of an individual and this resulted in convulsions and acute respiratory failure. We examined the effects of subarachnoid Urografin® injections on the rat central nervous system. The onset and frequency of the convulsions, as well as fatality, were dependent on the amount of Urografin® administered. No convulsions were observed in rats receiving injections of hypertonic NaCl solution or saline. The results confirmed that subarachnoid injections of Urografin® cause convulsions and death, as previously reported in human cases, and our study ascertained the causal relationship between the above malpractice and fatal outcomes.