Burden and correlates of readmissions related to pulmonary edema in US hemodialysis patients: a cohort study.

Background: Pulmonary edema is prevalent and may be a common cause of hospital readmissions in hemodialysis patients. We aimed to estimate the national burden of, and identify correlates of, readmissions related to pulmonary edema among hemodialysis patients. Methods: In this retrospective cohort study using national registry data, we identified prevalent US hemodialysis patients (n = 215 251) with index admissions while under Medicare primary coverage in 2011-13. We defined readmissions as admissions occurring within 30 days of the index discharge and pulmonary edema-related readmissions as readmissions with discharge diagnoses of fluid overload, heart failure or pulmonary edema. Multivariable logistic regression models were used to determine odds ratios (ORs) for pulmonary edema-related readmissions by patient and index admission characteristics. Results: About one-quarter (23%) of index hospital admissions were followed by a readmission, with nearly half (44%) of the readmissions being associated with pulmonary edema. The strongest independent correlate of pulmonary edema-related readmission was a pulmonary edema-related index admission [OR = 2.32; 95% confidence interval (CI) 2.22-2.41]. With the exception of dialysis vintage <1 year (OR = 1.18; 95% CI 1.14-1.22), chronic obstructive pulmonary disease (OR = 1.34; 95% CI 1.29-1.38), dialysis non-compliance (OR = 1.53; 95% CI 1.41-1.64) and congestive heart failure (OR = 1.85; 95% CI 1.77-1.93), patient characteristics were not generally associated with higher risk of pulmonary edema-related readmission. Conclusions: Readmissions related to pulmonary edema are common in hemodialysis patients. Interventions aimed at preventing such readmissions could have a substantial impact on readmissions overall, particularly targeted at incident hemodialysis patients with a prior history of heart failure and patients initially admitted for pulmonary edema.

TMPRSS13 deficiency impairs stratum corneum formation and epidermal barrier acquisition.

Membrane-anchored serine proteases serve as important regulators of multiple developmental and homoeostatic processes in mammals. TMPRSS13 (transmembrane protease, serine 13; also known as mosaic serine protease large-form, MSPL) is a membrane-anchored serine protease with unknown biological functions. In the present study, we used mice with the Tmprss13 gene disrupted by a ß-galactosidase-neomycin fusion gene insertion to study the expression and function of the membrane-anchored serine protease. High levels of Tmprss13 expression were found in the epithelia of the oral cavity, upper digestive tract and skin. Compatible with this expression pattern, Tmprss13-deficient mice displayed abnormal skin development, leading to a compromised barrier function, as measured by the transepidermal fluid loss rate of newborn mice. The present study provides the first biological function for the transmembrane serine protease TMPRSS13.

Early factors associated with fluid sequestration and outcomes of patients with acute pancreatitis.

BACKGROUND & AIMS: Predicting level of fluid sequestration could help identify patients with acute pancreatitis (AP) who need more or less aggressive fluid resuscitation. We investigated factors associated with level of fluid sequestration in the first 48 hours after hospital admission in patients with AP and effects on outcome. METHODS: We analyzed data from consecutive adult patients with AP admitted to the Brigham and Women's Hospital in Boston, Massachusetts, from June 2005 to December 2007 (n = 266) or the Alicante University General Hospital in Spain from September 2010 to December 2012 (n = 137). Level of fluid sequestration in the first 48 hours after hospital admission was calculated by subtracting the total amount of fluid administered and lost in the first 48 hours of hospitalization. Demographic and clinical variables obtained in the emergency department were analyzed to identify factors associated with level of fluid sequestration in the first 48 hours after hospital admission. Outcome assessed included length of hospital stay, acute fluid collection(s), pancreatic necrosis, persistent organ failure, and mortality. RESULTS: The median level of fluid sequestration in the first 48 hours after hospital admission was 3.2 L (1.4-5 L). The simple and multiple linear regression models showed that younger age, alcohol etiology, hematocrit, glucose, and systemic inflammatory response syndrome were significantly associated with increased levels of fluid sequestration in the first 48 hours after hospital admission. Increased level of fluid sequestration in the first 48 hours was significantly associated with longer hospital stays and higher rates of acute fluid collection, pancreatic necrosis, and persistent organ failure. There was a nonsignificant trend toward a higher level of fluid sequestration in the first 48 hours among patients who died. CONCLUSION: Age, alcoholic etiology of AP, hematocrit, glucose, and presence of systemic inflammatory response syndrome in the emergency department were independent predictors of increased levels of fluid sequestration in the first 48 hours after hospital admission. These patients have higher risks of local and systemic complications and longer hospital stays.

Increased interstitial protein because of impaired lymph drainage does not induce fibrosis and inflammation in lymphedema.

OBJECTIVE: The pathophysiology of lymphedema is incompletely understood. We asked how transcapillary fluid balance parameters and lymph flow are affected in a transgenic mouse model of primary lymphedema, which due to an inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) signaling lacks dermal lymphatics, and whether protein accumulation in the interstitium occurring in lymphedema results in inflammation. METHODS AND RESULTS: As estimated using a new optical-imaging technique, we found that this signaling defect resulted in lymph drainage in hind limb skin of K14-VEGFR-3-Ig mice that was 34% of the corresponding value in wild-type. The interstitial fluid pressure and tissue fluid volumes were significantly increased in the areas of visible swelling only, whereas the colloid osmotic pressure in plasma, and thus the colloid osmotic pressure gradient, was reduced compared to wild-type mice. An acute volume load resulted in an exaggerated interstitial fluid pressure response in transgenic mice. There was no accumulation of collagen or lipid in skin, suggesting that chronic edema presented in the K14-VEGFR-3-Ig mouse was not sufficient to induce changes in tissue composition. Proinflammatory cytokines (interleukin-2, interleukin-6, interleukin-12) in subcutaneous interstitial fluid and macrophage infiltration in skin of the paw were lower, whereas the monocyte/macrophage cell fraction in blood and spleen was higher in transgenic compared with wild-type mice. CONCLUSIONS: Our data suggest that a high interstitial protein concentration and longstanding edema is not sufficient to induce fibrosis and inflammation characteristic for the human condition and may have implications for our understanding of the pathophysiology of this condition.

Brain cell swelling during hypocapnia increases with hyperglycemia or ketosis.

BACKGROUND: Severe hypocapnia reduces cerebral blood flow (CBF) and is known to be a risk factor for diabetic ketoacidosis (DKA)-related cerebral edema and cerebral injury in children. Reductions in CBF resulting from hypocapnia alone, however, would not be expected to cause substantial cerebral injury. We hypothesized that either hyperglycemia or ketosis might alter the effects of hypocapnia on CBF and/or cerebral edema associated with CBF reduction. METHODS: We induced hypocapnia (pCO2 20 ± 3 mmHg) via mechanical ventilation in three groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451 ± 78 mg/dL), and 15 ketotic rats (ß-hydroxy butyrate 3.0 ± 1.0 mmol/L). We used magnetic resonance imaging to measure CBF and apparent diffusion coefficient (ADC) values in these groups and in 17 ventilated rats with normal pCO2 (40 ± 3 mmHg). In a subset (n = 35), after 2 h of hypocapnia, pCO2 levels were normalized (40 ± 3 mmHg) and ADC and CBF measurements were repeated. RESULTS: Declines in CBF with hypocapnia occurred in all groups. Normalization of pCO2 after hypocapnia resulted in hyperemia in the striatum. These effects were not substantially altered by hyperglycemia or ketosis. Declines in ADC (suggesting brain cell swelling) during hypocapnia, however, were greater during both hyperglycemia and ketosis. CONCLUSIONS: We conclude that brain cell swelling associated with hypocapnia is increased by both hyperglycemia and ketosis, suggesting that these metabolic conditions may make the brain more vulnerable to injury during hypocapnia.

Aqp2-expressing cells give rise to renal intercalated cells.

The mammalian collecting duct comprises principal and intercalated cells, which maintain sodium/water and acid/base balance, respectively, but the epigenetic contributors to the differentiation of these cell types remain unknown. Here, we investigated whether the histone H3 K79 methyltransferase Dot1l, which is highly expressed in principal cells, participates in this process. Taking advantage of the distribution of aquaporin 2 (Aqp2), which localizes to principal cells of the collecting duct, we developed mice lacking Dot1l in Aqp2-expressing cells (Dot1l(AC)) and found that these mice had approximately 20% fewer principal cells and 13%-16% more intercalated cells than control mice. This deletion of Dot1l in principal cells abolished histone H3 K79 methylation in these cells, but unexpectedly, most intercalated cells also had undetectable di-methyl K79, suggesting that Aqp2(+) cells give rise to intercalated cells. These Aqp2(+) cell-derived intercalated cells were present in both developing and mature kidneys. Furthermore, compared with control mice, Dot1l(AC) mice had 40% higher urine volume and 18% lower urine osmolarity with relatively normal electrolyte and acid-base homeostasis. In conclusion, these data suggest that Dot1l deletion facilitates the differentiation of some α- and ß-intercalated cells from Aqp2-expressing progenitor cells or mature principal cells.

Protean presentation and multiple challenges of nephrocalcinosis in pregnancy (six pregnancies in four patients).

BACKGROUND: Nephrocalcinosis is an umbrella term covering increased content of calcium salts in the renal parenchyma, interstitial damage and potential evolution towards renal failure. Pregnancy is often the first occasion for biochemical or imaging tests in young women and may allow early diagnosis. Conversely, even mild kidney disease may represent a challenge in pregnancy. AIM: The aim of this study was to report on four patients in whom nephrocalcinosis was first diagnosed during pregnancy, exemplifying the protean presentation and multiple challenges of nephrocalcinosis in pregnancy. METHODS: This is a case series study including data on all pregnancies prospectively gathered in the Nephrological-Obstetric Unit dedicated to pregnancy and kidney diseases (2000-11). RESULTS: Six pregnancies were observed in four patients (31-35 years; one twin pregnancy, one ongoing, one patient with three pregnancies). Symptoms were oedema in two (later developed in a further patient), renal functional impairment and electrolyte imbalance in two each. Two patients developed hypertension late in pregnancy. Electrolyte imbalance was life-threatening in one patient (severe acidosis, severe hyperkalaemia: 7.5 mEq/L). Delivery was by Caesarean section in three patients, preterm in one. Multiple or long hospitalizations for metabolic reasons were needed in three patients, the fourth was hospitalized for obstetric reasons. In all patients, diagnosis of nephrocalcinosis was made at ultrasounds during basic nephrological evaluation, confirmed at computerized tomography scan in three. The pathogenesis was linked to diuretic abuse in one case and to collagen disease, inborn errors and prematurity, possibly associated with diuretic misuse, in the others. CONCLUSION: Nephrocalcinosis may have protean presentations in pregnancy. The risk of severe electrolyte derangements, oedema and hypertension warrants strict clinical surveillance.

Hemodynamic and biochemical benefits of the objective measurement of fluid status in hemodialysis patients.

Subtle fluid imbalance can cause poor clinical outcomes among hemodialysis patients. However, the traditional subjective assessment of fluid status may be inadequate. We evaluated whether the objective measurement and optimization of fluid status could be beneficial for hemodynamic and biochemical parameters in hemodialysis patients. We enrolled 120 hemodialysis patients, who were clinically euvolemic for at least 3 months. Based on the results of a body composition monitor, we divided the patients into the following two groups: the hyperhydrated group (post hemodialysis fluid overload ≥ 1.1 L) and the dehydrated group (post hemodialysis fluid overload < -1.1 L). We reduced the patient's body weight in the hyperhydrated group and raised the body weight in the dehydrated group towards normohydration (-1.1 L ≤ fluid overload < 1.1 L) for 16 weeks. Forty-four of 120 patients were in the hyperhydrated group, and 18 of 120 patients in the dehydrated group. After 16 weeks, systolic blood pressure and pulse pressure decreased in the hyperhydrated group, while there was no increase in blood pressure in the dehydrated group after the intervention. Serum levels of monocyte chemotactic protein-1, an inflammatory marker, gradually decreased in the hyperhydrated group, and serum adiponectin levels, an anti-atherogenic biomarker, increased in the two groups. We found that hyperhydrated patients contributed over 1/3 of the participants despite enrolling clinically euvolemic patients and that body composition monitor-guided optimization of body fluid status may lead to improvement of inflammatory markers and anti-atherogenic adipokines as well as hemodynamic parameters in hemodialysis patients.

Maintenance and regulation of extracellular volume and the ion environment in Drosophila larval nerves.

In mammals and insects, paracellular blood barriers isolate the nervous system from the rest of the animal. Glia and accessory cells of the nervous system use pumps, channels, cotransporters, and exchangers collectively to maintain the extracellular ion environment and osmotic balance in the nervous system. At present, the molecular mechanisms that regulate this process remain unclear. In humans, loss of extracellular ion and volume regulation in the nervous system poses serious health threats. Drosophila is a model genetic organism with a proven track record for uncovering molecular mechanisms relevant to human health and disease. Here, we review what is known about extracellular ion and volume regulation in larval abdominal nerves, present some new data about the impact of neural activity on the extracellular environment, and relate the findings to mammalian systems. Homologies have been found at the level of morphology, physiology, molecular mechanisms, and mutant phenotypes. The Fray-Ncc69 module regulates extracellular volume in larval nerves. Genetic rescue experiments with the mammalian orthologs prove this module has a direct correlate in humans. This and other molecular homologies, together with the similar physiological needs, suggest that uncovering the molecular mechanisms of ion and volume regulation in larval nerves will likely provide significant insights into this process in mammalian systems.

Time-dependent changes in proinflammatory and neurotrophic responses of microglia and astrocytes in a rat model of osmotic demyelination syndrome.

Osmotic demyelination syndrome (ODS) is a serious demyelinating disease in the central nervous system usually caused by rapid correction of hyponatremia. In an animal model of ODS, we previously reported microglial accumulation expressing proinflammatory cytokines. Microglia and astrocytes secreting proinflammatory cytokines and neurotrophic factors are reported to be involved in the pathogenesis of demyelinative diseases. Therefore, to clarify the role of microglial and astrocytic function in ODS, we examined the time-dependent changes in distribution, morphology, proliferation, and mRNA/protein expression of proinflammatory cytokines, neurotrophic factors, and matrix metalloproteinase (MMP) in microglia and astrocytes 2 days (early phase) and 5 days (late phase) after the rapid correction of hyponatremia in ODS rats. The number of microglia time dependently increased at demyelinative lesion sites, proliferated, and expressed tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase, and MMP2, 9, and 12 at the early phase. Microglia also expressed leukemia inhibitory factor (a neurotrophic factor) and phagocytosed myelin debris at the late phase. The number of astrocytes time dependently increased around demyelinative lesions, extended processes to lesions, proliferated, and expressed nerve growth factor and glial cell line-derived neurotrophic factor at the late phase. Moreover, treatment with infliximab, a monoclonal antibody against TNF-α, significantly attenuated neurological impairments. Our results suggest that the role of microglia in ODS is time dependently shifted from detrimental to protective and that astrocytes play a protective role at the late phase. Modulation of excessive proinflammatory responses in microglia during the early phase after rapid correction may represent a therapeutic target for ODS.

Meniere's disease: new concepts, new treatments.

Our understanding of Meniere's disease is being revamped. For decades, the condition was thought to be caused by excessive fluid retention (hydrops) in the endolymphatic spaces of the inner ear, which led to tears or ruptures of the membranous structures that affect hearing and balance. More recently, research has shown that hydrops is not always associated with Meniere's and ought not to be considered the ultimate cause of its symptoms. New theories center on the fact that Meniere's disease may not have a single cause but may well be a common endpoint of a variety of anatomic or physiologic variables, including ischemic or even autoimmune injuries. This article describes the new thinking about Meniere's and explains why current treatment approaches, although they are based on outdated understanding, may still be valuable for alleviating symptoms in some patients.

Neurologic disease in a pig.

Three 4-week-old Yorkshire-Hampshire cross piglets from a litter of 9 (7 liveborn) developed convulsions the day of weaning. They were subsequently obtunded, ataxic, and hypermetric and had intention tremors. An affected male pig was presented live for necropsy on day 5 postweaning. This animal was euthanatized and necropsied. No significant grossly visible postmortem lesions were found. Histologic examination of the brain disclosed laminar necrosis of the submeningeal cerebral and cerebellar cortices with replacement by broad sheets of gitter cells. Occasional cerebral and cerebellar leptomeningeal and parenchymal vessels were surrounded by lymphocytes with fewer eosinophils. The morphologic diagnosis was severe multifocal subcortical cerebral and cerebellar laminar necrosis with moderate multifocal lymphocytic and eosinophilic cerebral and cerebellar leptomeningeal and parenchymal perivasculitis. The history and histologic findings are consistent with an etiologic diagnosis of sodium ion intoxication.

Bioimpedance spectroscopy for fluid status assessment in patients with decompensated liver cirrhosis: Implications for peritoneal dialysis.

Bioimpedance spectroscopy (BIS) is routinely used in peritoneal dialysis patients and might aid fluid status assessment in patients with liver cirrhosis, but the effect of ascites volume removal on BIS-readings is unknown. Here we determined changes in BIS-derived parameters and clinical signs of fluid overload from before to after abdominal paracentesis. Per our pre-specified sample size calculation, we studied 31 cirrhotic patients, analyzing demographics, labs and clinical parameters along with BIS results. Mean volume of the abdominal paracentesis was 7.8 ± 2.6 L. From pre-to post-paracentesis, extracellular volume (ECV) decreased (20.2 ± 5.2 L to 19.0 ± 4.8 L), total body volume decreased (39.8 ± 9.8 L to 37.8 ± 8.5 L) and adipose tissue mass decreased (38.4 ± 16.0 kg to 29.9 ± 12.9 kg; all p < 0.002). Correlation of BIS-derived parameters from pre to post-paracentesis ranged from R² = 0.26 for body cell mass to R² = 0.99 for ECV. Edema did not correlate with BIS-derived fluid overload (FO ≥ 15% ECV), which occurred in 16 patients (51.6%). In conclusion, BIS-derived information on fluid status did not coincide with clinical judgement. The changes in adipose tissue mass support the BIS-model assumption that fluid in the peritoneal cavity is not detectable, suggesting that ascites (or peritoneal dialysis fluid) mass should be subtracted from adipose tissue if BIS is used in patients with a full peritoneal cavity.

Prevalence and clinical demographics of cerebral salt wasting in patients with aneurysmal subarachnoid hemorrhage.

Hyponatremia is a frequent complication following subarachnoid hemorrhage (SAH), and is commonly attributed either to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome (CSW). The object of this study is to elucidate the clinical demographics and sequelae of hyponatremia due to CSW in subjects with aneurysmal SAH. Retrospective chart review of patients >18 years with aneurysmal SAH admitted between January 2004 and July 2007 was performed. Subjects with moderate to severe hyponatremia (serum sodium <130 mmol l(-1)) were divided into groups consistent with CSW and SIADH based on urine output, fluid balance, natriuresis, and response to saline infusion. Clinical demographics were compared. Of 316 subjects identified, hyponatremia (serum sodium <135 mmol l(-1)) was detected in 187 (59.2%) subjects and moderate to severe hyponatremia in 48 (15.2%). Of the latter group, 35.4% were categorized with SIADH and 22.9% with CSW. Compared to eunatremic subjects, hyponatremia was associated with significantly longer hospital stay (15.7 +/- 1.9 vs. 9.6 +/- 1.1 days, p < 0.001). Subjects with CSW had similar mortality and duration of hospital stay vs. those with SIADH. Though less common than SIADH, CSW was detected in approximately 23% of patients with history of aneurysmal SAH and was not clearly associated with enhanced morbidity and mortality compared to subjects with SIADH. Further studies regarding the pathogenesis and management, along with the medical consequences, of CSW are important.

Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia.

Thiazide diuretics enhance renal Na+ excretion by blocking the Na+-Cl- cotransporter (NCC), and mutations in NCC result in Gitelman syndrome. The mechanisms underlying the accompanying hypocalciuria and hypomagnesemia remain debated. Here, we show that enhanced passive Ca2+ transport in the proximal tubule rather than active Ca2+ transport in distal convolution explains thiazide-induced hypocalciuria. First, micropuncture experiments in mice demonstrated increased reabsorption of Na+ and Ca2+ in the proximal tubule during chronic hydrochlorothiazide (HCTZ) treatment, whereas Ca2+ reabsorption in distal convolution appeared unaffected. Second, HCTZ administration still induced hypocalciuria in transient receptor potential channel subfamily V, member 5-knockout (Trpv5-knockout) mice, in which active distal Ca2+ reabsorption is abolished due to inactivation of the epithelial Ca2+ channel Trpv5. Third, HCTZ upregulated the Na+/H+ exchanger, responsible for the majority of Na+ and, consequently, Ca2+ reabsorption in the proximal tubule, while the expression of proteins involved in active Ca2+ transport was unaltered. Fourth, experiments addressing the time-dependent effect of a single dose of HCTZ showed that the development of hypocalciuria parallels a compensatory increase in Na+ reabsorption secondary to an initial natriuresis. Hypomagnesemia developed during chronic HCTZ administration and in NCC-knockout mice, an animal model of Gitelman syndrome, accompanied by downregulation of the epithelial Mg2+ channel transient receptor potential channel subfamily M, member 6 (Trpm6). Thus, Trpm6 downregulation may represent a general mechanism involved in the pathogenesis of hypomagnesemia accompanying NCC inhibition or inactivation.

Mitochondrial dysfunction and oxidative stress are involved in the mechanism of methotrexate-induced renal injury and electrolytes imbalance.

Methotrexate is a folate analog used against a wide range of diseases including malignancies and autoimmune disorders. On the other hand, clinical use of the MTX is associated with kidney injury and renal failure. There is no clear mechanism for MTX-induced renal injury. The current investigation was designed to evaluate the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of MTX-induced renal injury. Rats received MTX (a single dose of 20 or 30 mg/kg, i.p). Five days after MTX administration, serum biomarkers of kidney injury and tissue markers of oxidative stress were assessed. Moreover, kidney mitochondria were isolated, and several mitochondrial indices were determined. MTX-treated animals developed biochemical evidence of renal injury as judged by elevated serum blood urea nitrogen (BUN), creatinine (Cr) and along with hypokalemia, hypophosphatemia, hypocalcemia, and a decrease in serum glucose, and uric acid. Moreover, MTX caused an increase in kidney reactive oxygen species and lipid peroxidation. Renal glutathione reservoirs were also depleted, and tissue antioxidant capacity was decreased in MTX-treated animals. Kidney histopathological changes including interstitial inflammation, renal tubular degeneration, retraction glomeruli, and vascular congestion were also evident in MTX-treated rats. On the other hand, it was found that mitochondrial parameters including mitochondrial membrane potential, mitochondrial dehydrogenases activity, and mitochondrial glutathione and ATP content were decreased, while lipid peroxidation and mitochondrial permeabilization were increased with MTX treatment. These data suggest a role for mitochondrial dysfunction and oxidative stress in the mechanism of MTX nephrotoxicity.

[Hyperosmolarity: Intracellular effects and implication in dry eye disease]. / Hyperosmolarité : effets intracellulaires et implication dans la sécheresse oculaire.

Dry eye disease is a multifactorial disease affecting the lacrimal functional unit and which has a significant impact on the quality of life of patients. This pathology works as a vicious circle at the ocular surface in which hyperosmolarity of the tear film plays a key role. This review intends to describe the different reported intracellular effects induced by hyperosmolarity in cells: alteration of cytoskeleton, cell cycle slowdown, adaptation mechanisms triggered as restoration of cell volume and accumulation of compatible osmolytes, the crucial role of the osmoprotectant factor Nuclear Factor of the Activated T cells-5 (NFAT5), apoptosis, as well as oxidative stress and inflammatory responses caused by this particular condition. Reported effects of hyperosmolarity in the experimental studies specific of dry eye disease concerning ocular surface cells will be described in parallel. Indeed, these data allow to understand a part of the pathophysiology of the disease, and specially the links between tear hyperosmolarity and inflammation of the ocular surface, the second key of the pathology phenomenon.

THE ROLE OF HISTAMINE IN THE MECHANISM OF ANTIBIOTIC-INDUCED CHANGES IN COLONIC ION AND WATER TRANSPORT.

The first time the role of histamine and H1-histamine receptors in the mechanisms of ceftriaxone-induced diarrhea in rats. Investigation of the flow of water and electrolytes through the epithelium of the colon performed male rats Wistar (180-250 g), isolated area by perfusion in vivo, for the actions of ceftriaxone (50 mg/kg intramuscularly), histamine (1,8; 3,6; 7,2 mg/ kg, introperytonealno, and 3,6 mg*kg-1 *h-1 intravenously) and loratadine (1,7 mg/kg, per os). Histamine intravenous administration, similar to ceftriaxone, makes a pro-secretory effect on the transport of water and sodium. Blockade of H1-histamine receptors loratadine prevents clinical signs ceftriaxone-induced diarrhea that accompanied the restoration of total water flow indicators and potassium through the epithelium of the colon of rats. Loratadine can be recommended for the prevention of diarrhea antybiotykasotsiyovanoyi not infectious etiology.

Renal aquaporin water channels: from molecules to human disease.

Following the discovery of the aquaporin-1 water channel in 1991, molecular techniques have been developed to examine the roles of renal aquaporins-1, -2, -3, and -4 in disorders of water balance. This article reviews current knowledge regarding aquaporin function and dysfunction in water-losing and water-retaining states.

Is hypertension a disorder of volume control? What is the evidence?

The etiological factors responsible for the hypertensive phenotype are complex and several experimental and clinical observations point to a major role of the kidney as being responsible. Genetic studies of uncommon diseases which express monogenetic inheritance all have in common a dysregulation of Na+ balance and volume expansion. Furthermore, epidemiological data suggest an increased incidence of hypertension in communities with high excretory rates of Na+. Experimental data also suggest that low birth weight is associated with an increase in the frequency of hypertension later in life and raises the possibility that intrauterine imprinting may contribute to the expression of the phenotype. Upregulation of the Na+/K+/2Cl- and thiazide-sensitive transporters in low birth weight animals may provide the physiological basis for these observations. In addition, low birth weight is associated with a decrease in nephron number. Therefore, low nephron number may induce adaptive changes in utero which influence volume homeostasis later in life and subtle gain of function mutations in one or more of these transporters may unmask defects in volume homeostasis with increasing salt intake. Finally, the high prevalence of hypertension in functionally anephric patience seems to respond to sustained maintenance of 'dry weight' through ultrafiltration.