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Background: Congestion is the hallmark clinical manifestation of heart failure (HF) syndrome and a strong predictor of poor outcomes. Despite rapid improvements in volume status during the hospital course, about half of all patients are discharged with residual congestion, which significantly increases the risk of readmission and affects survival. Although nurse-led disease management programs (DMP) improve outcomes, patients may not be offered this level of support, often because of limited resources. Risk stratification to target DMP to high risk patients is essential; nevertheless, despite DMP and risk assessment, readmission due to re-congestion remains frequent, possibly linked to insufficient decongestion at index discharge. Thus, there is an imperative to ensure euvolemia pre-discharge and monitor post-discharge for early detection of re-congestion. To date, pre-discharge euvolemia is usually based on subjective clinical assessment, which is sometimes inaccurate. Therefore, applying sensitive congestion assessments pre-discharge may help to detect residual congestion and guide the administration of diuretic treatment before and after hospital discharge, during DMP home visits – we call this strategy “DMP-plus”. The primary focus of this thesis was guided decongestion and early detection of deterioration. Hypothesis It is hypothesised that targeting high risk patients (i.e., 33% risk or more) at an enhanced post-discharge, nurse-led DMP, comprised of ultrasound-guided decongestion and constant patient monitoring using mobile health (m-Health), will improve short-term adverse outcomes in patients admitted for ADHF. Objectives: i. To evaluate novel non-invasive congestion assessments and establish the most practical that can be applied to all patients by any health practitioner. ii. To use technological advances to: a) detect, track and eliminate congestion with a portable, non-invasive assessment and b) enhance patient monitoring with an m-Health digital HF ava

Background and Aims: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis with no established clinical guidelines. We sought to define the clinical outcomes of patients presenting with HH managed with current standards-of-care. Method(s): International Classification of Diseases-10 codes identified cirrhotic patients with HH presenting to 3 tertiary centres (Melbourne, Australia) from 2010 to 2018. HH was defined as pleural effusion in the absence of cardiopulmonary disease. Medical records were reviewed to determine baseline characteristics and survival. Primary outcome was 12-month mortality. The Kaplan-Meier method was used to calculate survival probability. Result(s): 83 patients were included. Median age was 59 years (IQR 54-63), 57% were male and median MELD score was 29 (IQR 25-33). Common causes of cirrhosis were viral (33%), alcohol (27%) and nonalcoholic fatty liver disease (19%); 29% had hepatocellular carcinoma. Pleural effusions were typically right-sided (83%) and 73% had concurrent ascites. There were 169 hospital admissions for HH over the study period. Median length of stay was 11 days and 22% required intensive care unit admission. 89% and 7% patients were prescribed diuretics and non-selective beta-blockers respectively at presentation. Diuretic therapy alone was commenced in 13 (8%) presentations while 120 (71%) received diuresis and pleurocentesis (median 3L drained); 17% required blood products to facilitate pleurocentesis. 23 patients received intercostal drain insertion, 1 pleurodesis and 10 proceeded to transjugular intrahepatic portosystemic shunt insertion. 31 (37%) patients underwent liver transplantation (OLT). Significant complications were observed in 45% of admissions, including: infection [n = 25], hepatic encephalopathy [n = 19] and pneumothorax [n = 11]. 86% patients required re-admission within 6-months of index admission. The 12-month mortality rate was 29% (n = 24) and probability of transpla

Background and Aim: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis, with no established clinical guidelines.We sought to define the clinical outcomes of patients presenting with HH and managed with current standards of care. Method(s): ICD-10 codes identified cirrhotic patients with HH presenting to three tertiary centers in Melbourne, Australia, from 2010 to 2018. HH was defined as pleural effusion in the absence of cardiopulmonary disease. Medical records were reviewed to determine baseline characteristics and survival. The primary outcome was 12-month mortality. The Kaplan- Meier method was used to calculate survival probability. Result(s): A total of 82 patients were included (median age, 59 years [IQR, 54-63]; 56% male; median Model for End-Stage Liver Disease score, 29 [IQR, 25-33]). Common causes of cirrhosis were viral (33%), non-alcoholic fatty liver disease (19%), and alcohol (16%); 29% of patients had hepatocellular carcinoma. Pleural effusions were typically right-sided (85%), and 73% had concurrent ascites. There were 169 hospital admissions for HH during the study period. Mean length of stay was 12 days, and 27% required intensive care unit admission. At presentation, 89% and 7% of patients were prescribed diuretics and non-selective betablockers, respectively. Diuretic therapy alone was commenced in 13 presentations (8%), while 120 patients (71%) received diuresis and pleurocentesis (median, 3 L drained); 25% required blood products to facilitate pleurocentesis. Twenty-three patients received intercostal drain insertion, one had pleurodesis, and 10 proceeded to transjugular intrahepatic portosystemic shunt insertion. There were 24 patients (29%) who underwent orthotopic liver transplantation (OLT). Significant complications were observed in 46% of admissions, including acute kidney injury (n = 54), infection (n = 28), hepatic encephalopathy (n = 21), and pneumothorax (n = 11). Overall, 83% of patients require

Ischemic damage to brain cells results from a significant decrease in arterial blood flow to brain tissue or as a result of a long or shortening of the blood vessels in the brain. The result of these processes is focal or diffuse brain injury. A clear violation of microcirculation leads to several microinfarctions and occlusive lesions of large arteries - extensive cerebral infarctions

In the present study, we explored the therapeutic potential of bioreactor-grown cell cultures of the medicinal plant species Dioscorea deltoidea, Tribulus terrestris and Panax japonicus to treat carbohydrate metabolism disorders (CMDs) in laboratory rats. In the adrenaline model of hyperglycemia, aqueous suspensions of cell biomass pre-administered at a dose of 100 mg dry biomass/kg significantly reduced glucose level in animal blood 1–2.5 h (D. deltoidea and T. terrestris) or 1 h (P. japonicus) after adrenaline hydrochloride administration. In a streptozotocin-induced model of type 2 diabetes mellitus, the cell biomass of D. deltoidea and T. terrestris acted towards normalization of carbohydrate and lipid metabolism, as evidenced by a significant reduction of daily diuresis (by 39– 57%), blood-glucose level (by 46–51%), blood content in urine (by 78–80%) and total cholesterol (25– 36%) compared to animals without treatment. Bioactive secondary metabolites identified in the cell cultures and potentially responsible for their actions were deltoside, 25(S)-protodioscin and protodioscin in D. deltoidea; furostanol-type steroidal glycosides and quinic acid derivatives in T. terrestris; and ginsenosides and malonyl-ginsenosides in P. japonicus. These results evidenced for high potential of bioreactor-grown cell suspensions of these species for prevention and treatment of CMD, which requires further investigation. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This.

BACKGROUND: Animal models implicate FGF-23 (fibroblast growth factor-23) as a direct contributor to adverse cardiorenal interactions such as sodium avidity, diuretic resistance, and neurohormonal activation, but this has not been conclusively demonstrated in humans. Therefore, we aimed to evaluate whether FGF-23 is associated with parameters of cardiorenal dysfunction in humans with heart failure, independent of confounding factors. METHODS: One hundred ninety-nine outpatients with heart failure undergoing diuretic treatment at the Yale Transitional Care Center were enrolled and underwent blood collection, and urine sampling before and after diuretics. RESULTS: FGF-23 was associated with several metrics of disease severity such as higher home loop diuretic dose and NT-proBNP (N-terminal pro-B-type natriuretic peptide), and lower estimated glomerular filtration rate, serum chloride, and serum albumin. Multivariable analysis demonstrated no statistically significant association between FGF-23 and sodium avidity measured by fractional excretion of sodium, or proximal or distal tubular sodium reabsorption, either before diuretic administration or at peak diuresis (P≥0.11 for all). Likewise, FGF-23 was not independently associated with parameters of diuretic resistance (diuretic excretion, cumulative urine and sodium output, and loop diuretic efficiency [P≥0.33 for all]) or neurohormonal activation (plasma or urine renin [P≥0.36 for all]). Moreover, the upper boundary of the 95% CI of all the partial correlations were ≤0.30, supporting the lack of meaningful correlations. FGF-23 was not associated with mortality in multivariable analysis (P=0.44). CONCLUSIONS: FGF-23 was not meaningfully associated with any cardiorenal parameter in patients with heart failure. While our methods cannot rule out a small effect, FGF-23 is unlikely to be a primary driver of cardiorenal interactions.

Introduction: We aimed to study the effects of daily variation in solute intake on urine volume in patients with syndrome of inappropriate secretion of antidiuretic hormone secretion (SIADH), syndrome of nephrogenic antidiuresis (NSIAD), central diabetes insipidus (CDI), or nephrogenic diabetes insipidus (NDI). Materials and methods: In 6 patients with CDI, 7 patients with NDI, 7 patients with SIADH, and 2 patients with NSIAD we had the opportunity to have 24-hour urine collections during normal diet before any treatment. We had two 24-hour urine collections with a difference of at least 20% in solute output (measured by the formula urine osmolality × urine volume). In 1 patient with NDI taking a high protein diet we analyzed the effect of a normal protein intake on diuresis. With respect to patients with NDI and CDI we included only patients with a urine osmolality lower than 110 mOsm/kgH2O, and for SIADH/NSIAD we included only patients with a urine osmolality between 500 and 700 mOsm/kgH2O. Results: When the data of the patients with CDI/NDI were pooled, a high correlation between urine volume and solute output was observed (R = 0.83; p < 0.001). In 1 patient with X-linked NDI, we decreased urine volume simply by decreasing protein intake. If we pooled the data concerning SIADH/NSIAD, a correlation was observed between urine volume and solute output (R = 0.94; p < 0.001). As expected, increasing solute intake is beneficial in SIADH/NSIAD, while decreasing it decreases diuresis in NDI. Conclusion: Daily variations in solute output affect urine volume in NDI/CDI/SIADH/NSIAD, this could affect serum sodium (SNa) despite no variation in fluid intake. In SIADH, if solute intake is lower than usual for a few days it may significantly influence the SNa level despite no variation in fluid intake., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Key pointsAcclimatization to hypoxia leads to a reduction in plasma volume (PV) that restores arterial O-2 content.Findings from studies investigating the mechanisms underlying this PV contraction have been controversial, possibly as experimental conditions were inadequately controlled.We examined the mechanisms underlying the PV contraction evoked by 4 days of exposure to hypobaric hypoxia (HH) in 11 healthy lowlanders, while strictly controlling water intake, diet, temperature and physical activity.Exposure to HH-induced an similar to 10% PV contraction that was accompanied by a reduction in total circulating protein mass, whereas diuretic fluid loss and total body water remained unchanged.Our data support an oncotically driven fluid redistribution from the intra- to the extravascular space, rather than fluid loss, as the mechanism underlying HH-induced PV contraction.Extended hypoxic exposure reduces plasma volume (PV). The mechanisms underlying this effect are controversial, possibly as previous studies have been confounded by inconsistent experimental conditions. Here, we investigated the effect of hypobaric hypoxia (HH) on PV in a cross-over study that strictly controlled for diet, water intake, physical activity and temperature. Eleven males completed two 4-day sojourns in a hypobaric chamber, one in normoxia (NX) and one in HH equivalent to 3500 m altitude. PV, urine output, volume-regulating hormones and plasma protein concentration were determined daily. Total body water (TBW) was determined at the end of both sojourns by deuterium dilution. Although PV was 8.1 +/- 5.8% lower in HH than in NX after 24 h and remained similar to 10% lower thereafter (all P <0.002), no differences were detected in TBW (P = 0.17) or in 24 h urine volumes (all P > 0.23). Plasma renin activity and circulating aldosterone were suppressed in HH during the first half of the sojourn (all P <0.05) but thereafter similar to NX, whe

Aims: Sodium–glucose co-transporter 2 (SGLT2) inhibitors improve clinical outcome in patients with heart failure (HF), but the mechanisms behind their beneficial effects are not yet fully understood. We examined the effects of empagliflozin on renal sodium and glucose handling in patients with acute HF. Methods and results: This study was a pre-defined sub-study of a double-blind, randomized, placebo-controlled, multicentre study (EMPA-RESPONSE-AHF). Patients were allocated within 24 h of an acute HF admission to either empagliflozin 10 mg/day (n = 40) or placebo (n = 39) for 30 days. Markers of glucose and sodium handling were measured daily during the first 96 h and at day 30. Patients were 76 (range 38–89) years old and 33% had diabetes. The use of loop diuretics during the first 96 h was similar in both groups. Empagliflozin increased fractional glucose excretion with a peak after 24 h (21.8% vs. 0.1%; P < 0.001), without affecting plasma glucose concentration, while fractional sodium and chloride excretion and urinary osmolality remained unchanged (P >0.3 for all). However, empagliflozin increased plasma osmolality (delta osmolality at 72 h: 5 ± 8 vs. 2 ± 5 mOsm/kg; P = 0.049). Finally, there was an early decline in estimated glomerular filtration rate with empagliflozin vs. placebo (−10 ± 12 vs. −2 ± 12 mL/min/1.73 m2; P = 0.009), which recovered within 30 days. Conclusion: In patients with acute HF, empagliflozin increased fractional glucose excretion and plasma osmolality, without affecting fractional sodium excretion or urine osmolality and caused a temporary decline in estimated glomerular filtration rate. This suggests that empagliflozin stimulates osmotic diuresis through increased glycosuria rather than natriuresis in patients with acute HF.

Platypnea-orthodeoxia syndrome (POS) is a rare condition characterized by dyspnoea and deoxygenation in an upright position that is relieved by supine positioning. There are only five published accounts of it occurring post-lobectomy. We present the case of a 72-year-old male with 3 months of supposedly unexplained dyspnoea after right lower lobectomy for lung cancer who was confirmed to have POS. We highlight the importance of recognition and management as well as provide a brief summary of the pathophysiology.Copyright © The Author(s) 2019.

Background: In hyponatremia, due to the inappropriate secretion of antidiuretic hormone (SIADH), a high versus low solute intake will affect the urine volume (UV) and, hence, the SNa level. The clinical implication of the fractional solute excretion is presented. Methods: In 35 normal controls and 24 patients with SIADH and urine osmolality higher than serum osmolality, we compared exact solute intake obtained from 24 h urine collection, with the estimated value obtained on a urine morning spot sample by the formula: eGFR (L/min) × Sosm × 1440 × FE.Osm (%) = mmol/24 h. The exact UV was compared with the estimated value given by the formula: eGFR × 1440 × S.Creat/U.Creat (for eGFR the MDRD was used). In 65 patients with chronic SIADH, from which a morning spot urine sample was available, we determined the estimated fluid and solute intake. Results: A good correlation was observed between the measured solute output or urine volume and the estimated values obtained from the controls (r = 0.86) as well as in SIADH (r = 0.91). Conclusion: Patients with low solute intake (FE.Osm <1.4%) and low diuresis (V/eCcr <0.8%) should increase their intake by taking oral urea, for example. Patients with high solute intake (FE.Osm >2.5%) and high diuresis (V/eCcr >1.5%) could usually be treated by mild water restriction (<1.5-21/24 h)., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Fluid bolus (FB) contribute to positive fluid balance and may not have a beneficial effect. Following cardiac surgery FB are common but often based on simple physiology (heart rate, blood pressure, urine output) as measures of fluid responsiveness are more complex and may not be valid in this cohort. Method(s): Post-operative cardiac surgical patients who received a FB in ICU in the first 24 hours were included. Using a questionnaire based tool, the reasons for a FB and the perceived efficacy by the prescriber were recorded. Physiological data were recorded before and one hour after each FB. A FB was said to be "mean arterial pressure (MAP) responsive" if the FB caused a sustained increase in MAP of at least 5 mmHg. Result(s): Over 5 months, 74 patients (95% on-pump surgery) were recruited. A total of 135 FBs were administered. Each patient received a median of 1(1-2) FB, with a median volume of 0.25 (0.25-0.5) liters. Postoperatively 47% of patients received one FB, 31% received two FBs and 22% received three or more FBs. The most common fluid used was 4% albumin (85%). The main reasons for giving a FB were low MAP (72%), low urine output (21%) and low filling pressure (11%). Overall, 1 hour after a FB, there was an increase in MAP and central venous pressure, and a decrease in urine output, hemoglobin and serum calcium level. However, there was no change in heart rate, vasopressor rate, central venous oxygen saturation or serum lactate levels (Table). Overall, FBs contributed to 45% of fluid balance and only 48% of FB were MAP responsive. Conclusion(s): Lower MAP was the most common reason for FB and sustained physiological efficacy of FB were small.

Aquaporins (AQPs) are proteins that span plasma membranes allowing the movement of water and small solutes into or out of cells. The type, expression levels and activity of AQPs play a major role in the relative permeability of each cell to water or other solutes. Research on arthropod AQPs has expanded in the last 10 years due to the completion of several arthropod genome projects and the increased availability of genetic information accessible through other resources such as de novo transcriptome assemblies. In particular, there has been significant advancement in elucidating the roles that AQPs serve in relation to the physiology of blood-feeding arthropods of medical importance. The focus of this review is upon the significance of AQPs in relation to hematophagy in arthropods. This will be accomplished via a narrative describing AQP functions during the life history of hematophagic arthropods that includes the following critical phases: (1) Saliva production necessary to blood feeding, (2) Intake and excretion of water during blood digestion, (3) Reproduction and egg development and (4) Off-host environmental stress tolerance. The concentration on these phases will highlight known vulnerabilities in the biology of hematophagic arthropods that could be used to develop novel control strategies as well as research topics that have yet to be examined.

Polyphenols from Hibiscus sabdariffa calices were administered to patients with metabolic syndrome (125 mg/kg/day for 4 wk, n = 31) and spontaneously hypertensive rats (125 or 60 mg/kg in a single dose or daily for 1 wk, n = 8 for each experimental group). The H. sabdariffa extract improved metabolism, displayed potent anti-inflammatory and antioxidant activities, and significantly reduced blood pressure in both humans and rats. Diuresis and inhibition of the angiotensin I-converting enzyme were found to be less important mechanisms than those related to the antioxidant, anti-inflammatory, and endothelium-dependent effects to explain the beneficial actions. Notably, polyphenols induced a favorable endothelial response that should be considered in the management of metabolic cardiovascular risks. © 2014 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

CONTEXT: Verbascum nigrum L. (Scrophulariaceae) is a perennial plant used in folk medicine for the treatment of kidney diseases due to its presumable diuretic properties. OBJECTIVE: We investigated the diuretic activity and toxicity of extracts from different parts of V. nigrum and identified a group of compounds responsible for the biological effect. MATERIALS AND METHODS: Five ethanol extracts from herb, roots, flowers, leaves and stems as well as five fractions of polar compounds isolated from herb of V. nigrum were orally administrated as a single dose of 50 mg/kg to rats. Urinary excretion and electrolyte content were measured at 3 and 6 h after the treatment. The acute toxicity of the V. nigrum extracts and fractions was evaluated in mice.RESULTS: All extracts, except the one prepared from the roots, showed a significant increase of the urine output within first 3 h after their administration. The extract from stems was the most active, inducing urine output of 14.6 ± 0.8 ml/kg BW versus 5.2 ± 1.4 ml/kg BW of the control. It also demonstrated saluretic activity with a natriuretic index 4.1 and a kaliuretic index 3.8. The diuretic activity was correlated with the flavonoid content in the plant organs. Flavonoid fractions demonstrated significant activity; the higher content of flavonoids (expressed as hesperidin) translated into more pronounced diuretic (35.9 ± 2.1 ml/kg BW) and saluretic effects (natriuretic index 4.5 and kaliuretic index 5.4). CONCLUSION: The diuretic activity of traditionally used V. nigrum was validated experimentally. The pharmacological effect was attributed to flavonoids, which accumulated in aerial parts of the plant, mainly in stems.

Background. Hyaluronan (HA) is the dominant glycosaminoglycan in the renomedullary interstitium. Renomedullary HA has been implicated in tubular fluid handling due to its water-attracting properties and the changes occurring in parallel to acute variations in the body hydration status. less thanbrgreater than less thanbrgreater thanMethods. HA production was inhibited by 4-methylumbelliferone (4-MU in drinking water for 5 days, 1.45 +/- 0.07 g/day/kg body weight) in rats prior to hydration. less thanbrgreater than less thanbrgreater thanResults. Following hypotonic hydration for 135 min in control animals, diuresis and osmotic excretion increased while sodium excretion and glomerular filtration rate (GFR) remained unchanged. The medullary and cortical HA contents were 7.85 +/- 1.29 ng/mg protein and 0.08 +/- 0.01 ng/mg protein, respectively. Medullary HA content after 4-MU was 38% of that in controls (2.98 +/- 0.95 ng/g protein, p andlt; 0.05), while the low cortical levels were unaffected. Baseline urine flow was not different from that in controls. The diuretic response to hydration was, however, only 51% of that in controls (157 +/- 36 versus 306 +/- 54 mu l/g kidney weight/135 min, p andlt; 0.05) and the osmolar excretion only 47% of that in controls (174 +/- 47 versus 374 +/- 41 mu Osm/g kidney weight/135 min, p andlt; 0.05). Sodium excretion, GFR, and arterial blood pressure were similar to that in control rats and unaltered during hydration. less thanbrgreater than less thanbrgreater thanConclusions. Reduction of renomedullary interstitial HA using 4-MU reduces the ability of the kidney to respond appropriately upon acute hydration. The results strengthen the concept of renomedullary HA as a modulator of tubular fluid handling by changing the physicochemical properties of the interstitial space., Funding Agencies|Swedish Research Council

Sandflies (Phlebotominae, Nematocera, Diptera) are responsible for transmission of leishmaniasis and other protozoan-borne diseases in humans, and these insects depend on the regulation of water balance to cope with the sudden and enormous intake of blood over a very short time period. The sandfly inventory of neuropeptides, including those that regulate diuretic processes, is completely unknown. Direct MALDI-TOF/TOF mass spectrometric analysis of dissected ganglia of Phlebotomus papatasi, combined with a data-mining of sandfly genome contigs, was used to identify native CAPA-peptides, a peptide class associated with the regulation of diuresis in other hematophagous insects. The CAPA-peptides identified in this study include two CAPA-PVKs, differentially processed CAPA-PK, and an additional CAPA precursor peptide. The mass spectrometric analysis of different parts of the neuroendocrine system of the sandfly indicate that it represents the first insect which accumulates CAPA-PVKs exclusively in hormone release sites of abdominal ganglia and CAPA-PK (nearly) exclusively in the corpora cardiaca. Additionally, sandflies feature the smallest abdominal ganglia (35 micro m) where CAPA-peptides could be detected so far. The small size of the abdominal ganglia does not appear to affect the development of the median neurosecretory system as it obviously does in another comparably small insect species, Nasonia vitripennis, in which no capa-gene expression was found. Rather, immunocytochemical analyses confirm that the general architecture in sandflies appears identical to that of much larger mosquitoes., Published in Peptides, 2012.

gamma-L-Glutamyl-L-dopa (gludopa) is a dopamine (DA) prodrug with a high degree of renal selectivity. We compared the acute renal effects of gludopa in conscious control rabbits (n = 6) and rabbits with doxorubicin-induced congestive heart failure (CHF, n = 5). Normal saline and gludopa 25 and 100 mug/kg/min were infused intravenously (i.v.), each for 60 min. One week later, the same protocol was followed except that the DA-1 antagonist SCH 23390 was given i.v. in a dose of 0.3 mg/kg 10 min before gludopa infusion. An additional control group (n = 6) received the DA-1 antagonist alone and saline vehicle infusion throughout the study period. In both control and CHF groups, gludopa elicited significant and similar increases in urine flow (70, 62%), sodium excretion (127, 98%), and renal blood flow (RBF) (33, 27%), and decreased renal vascular resistance (RVR) (-23, -38%). All these changes were abolished by previous DA-1 antagonism with SCH 23390. Blood pressure (BP), heart rate (HR), and hindlimb blood flow (HBF) remained unchanged during gludopa infusion in both groups. In the control group, but not in the CHF group, plasma renin activity (PRA) increased during gludopa infusion; this was not influenced by DA-1 antagonism. In normal rabbits (n = 6), treatment with SCH 23390 alone had no significant effect on renal excretory function or haemodynamics. During gludopa administration, plasma DA concentration was not significantly altered, whereas urine DA excretion and renal DA content were markedly increased. Intrarenal conversion of gludopa to DA was significantly less in CHF rabbits as compared with the control group. Acute administration of gludopa produced renal vasodilation, natriuresis, and diuresis in rabbits with doxorubicin-induced CHF, similar to that observed in normal rabbits. These responses were mediated by intrarenally generated DA through DA-1 receptors.

Severe lithium intoxication, whether accidental or deliberate, is associated with significant morbidity and mortality and therefore qualifies as a medical emergency. Treatment has generally been aimed at enhancing the excretion of lithium from the body. Forced diuresis, although modestly enhancing lithium excretion, is of limited efficacy. Excellent lithium clearances are obtained with haemodialysis. However, significant problems with this technique exist, including its restricted availability and a rebound rise in lithium levels after its cessation, in addition to hypotension, electrolyte imbalances, and other haemodialysis technique specific complications. New continuous dialytic techniques, such as acute continuous haemodiafiltration, presently used in critically ill patients with established acute renal failure, also offer highly effective extraction of lithium whilst avoiding many of the difficulties encountered with conventional haemodialysis techniques. Such advances in dialytic therapies for the critically ill offer a significant advance in the treatment of severe lithium intoxication.

Background: With advances in neonatal intensive care, increasing numbers of preterm neonates are now surviving. In the past they would have died before there was time to develop chronic lung disease (CLD). Based on the definition of a neonate requiring any form of respiratory therapy (oxygen or assisted ventilation) at 36 weeks' post-menstrual age, the CLD rate in Australia is 52% in those <28 weeks and 12% in those 28-32 weeks gestation. The high CLD rate in the former group is due to their improved survival rates (one-year survival rate of infants born in the State of Victoria is 41% at 23 and 24 weeks, 73% at 25 weeks, and 88% at 26 weeks). Data sources: Randomized controlled trials (RCTs), including meta-analyses and Cochrane reviews on the prevention and treatment of CLD were identified in the published literature. Result(s): The following perinatal strategies were found to be effective in preventing or minimizing CLD: antenatal corticosteroids, postnatal surfactant, reduced oxygen saturation targeting at 89%-94%, early use of continuous positive airway pressure, synchronized ventilation, permissive hypercapnia ventilation strategy, high frequency oscillatory ventilation, closure of symptomatic patent ductus arteriosus with indomethacin, reduced fluid intake, and inhaled nitric oxide. Several anti-inflammatory and anti-oxidant agents have been found in RCTs to be effective, including vitamin A and recombinant human superoxide dismutase. Clinical management after the development of CLD includes appropriate oxygen and ventilation strategies, fluid restriction, and diuretic and bronchodilator therapy. Postnatal corticosteroid therapy is efficacious but its side-effect is increasing. The risk of cerebral palsy outweighs the benefit of therapy. Only in severe CLD, low-dose and short-course dexamethasone should be used. Conclusion(s): Ongoing basic and clinical research is required to identify perinatal and neonatal interventions that are effective in either preventi

Summary Patients with burn injuries involving more than 20 percent of the total body surface area lose a lot of fluid and are in the risk of developing a severe hypovolemia. Fluid resuscitation is a corner stone in burn care and is important for preventingfurthercomplications. The most common resuscitation formula is the Parkland Formula. Hourly urine output is a measure used to evaluate if the fluid given is sufficient enough to maintain a sustainable tissue perfusion. Inhalation injury, abuse of alcohol and drugs are some of the factors that may increase the amountoffluid needed. The purposefor this study is to study thecompliance to fluid resuscitation guidelines at a burn unit and which factors lead to deviation from the guidelines. Patient charts for 38 patients with burn injury >20%, > 18 years of age with a length of stay >48 hours, were reviewed regarding size of burn injury, hourly amount of fluid given, hourly urine output and presence of inhalation injury.Statistic significancewas found between the mean values of the differences in percentage between actual and calculated fluid amount for the first 24 hours. The differences in percentage between actual and calculated hourly urine output did not reach statistic significance. The result shows complianceto the fluid resuscitation guidelines. A larger sample would be required in order to investigate which factors causing deviations from the guidelines.

Nos flebotomíneos (Diptera: Psychodidae) o hábito pela hematofagia é responsável pela indução de vários processos fisiológicos também na transmissão de Leishmania Ross. O presente estudo compara o sangue de ave, de mamífero e com infecção por Leishmania amazonensis Lainson & Shaw sobre o potencial biológico de Lutzomyia migonei (França) e de Lutzomyia ovallesi Ortiz. Foram utilizadas fêmeas das duas espécies alimentadas artificialmente com sangue de hamster (Mesocricetus auratus Waterhouse) e frango (Gallus gallus Linnaeus), infectados com L. amazonensis. Os grupos controle foram alimentados somente com sangue, sem parasitas. Foram determinados o grau de repasto sanguíneo, o tempo de digestão, o padrão de diurese, o tempo de oviposição, a sobrevivencia a oviposição e a fecundidade. A espécie L. migonei quando alimentada com sangue de hamster e frango apresentaram maior fecundidade do que as fêmeas de L. ovallesi, a maior fecundidade foi com sangue de frango. A presença de Leishmania no sangue de frango ou sangue de hamster diminuiu significativamente o seu consumo, o que resultou na diminuição da sobrevida das fêmeas após a oviposição em L. migonei alimentados com sangue de frango e não com sangue de hamsters. Entretanto, não afetar a quantidade de sangue e a sobrevivência de oviposição de L. ovallesi. A infecção com L. amazonensis causo um aumento no número de ovos retidos e diminuiu o número de ovos postos por L. migonei e L. ovallesi, especialmente com sangue de frango e também reduz o tempo de digestão do sangue em ambas as espécies com sangue de frango, mas não com sangue de hamster. Embora o sangue de frango foi menos eficaz do que o sangue de hamster sobre o potencial biológico de L. migonei e L. ovallesi, não exclui o sangue de frango como uma fonte de sangue para a manutenção das populações de ambas as espécies nas casas., En los flebótomos (Diptera: Psychodidae), la ingesta sanguínea es responsable de la inducción de varios procesos fisiológicos y es determinante en la transmisión de Leishmania Ross. El presente trabajo estudia la sangre de ave, de mamífero y mezclada con Leishmania amazonensis Lainson & Shaw sobre el potencial biológico de Lutzomyia migonei França y Lutzomyia ovallesi Ortiz. Se utilizaron hembras de ambas especies alimentadas artificialmente con sangre de hámster (Mesocricetus auratus Waterhouse) y de pollo (Gallus gallus Linnaeus), mezclada con L. amazonensis. Los grupos controles fueron hembras alimentadas sólo con sangre. Se determinó el grado de ingurgitación sanguínea, el tiempo de digestión sanguínea, el modelo de diuresis, el tiempo de oviposición, la sobrevivencia a la ovipostura y la fecundidad. L. migonei alimentadas con ambos tipos de sangre presentó mayor fecundidad que las hembras de L. ovallesi, la mayor fecundidad se registró con sangre de pollo. La presencia de Leishmania en la sangre de pollo o hámster disminuyó significativamente la masa sanguínea ingerida y redujo la sobrevivencia a la ovipostura en las hembras de L. migonei alimentadas con sangre de pollo y no con sangre de hámster. Sin embargo, no afectó la masa sanguínea ingerida, ni la sobrevivencia a la ovipostura de L. ovallesi. Mientras que la infección con L. amazonensis aumentó la cantidad de huevos retenidos y disminuyó el número de huevos puestos por L. migonei y por L. ovallesi en especial con sangre de pollo. Además, disminuyó el tiempo de digestión sanguínea en ambas especies alimentadas con sangre de pollo, pero no con la sangre de hámster. Aunque la sangre de pollo fue menos efectiva que la sangre de hámster sobre el potencial biológico de L. migonei y L. ovallesi, no se descarta a la sangre de pollo como una fuente sanguínea importante en el mantenimiento de las poblaciones de ambas especies en el peridomicilio.

Introduction: Extensive burn injury has systemic consequences due to capillary leak. After restoration of cellular integrity, infused fluid volume has to be removed partially. This can provoke electrolyte disorders. Purpose: We investigated the effect of progressive fluid removal on serum sodium level.Method: Retrospective study. Patients admitted to a burn unit were analyzed and separated in two groups without (Group A) or with (Group B) prolonged hypernatremia. Daily infusion-diuresis-ratio (IDR) was analyzed.Results: Fourty (12 female; 28 male) patients with a mean age of 47±19 years, a total burn surface area (TBSA) of 26±12%, and a mean abbreviated burned severity index (ABSI) score of 7.3±2 were included. In Group A 25 patients with a mean age of 47±18 years, a mean TBSA of 23±11%, and a mean ABSI score of 6.9±2.1 were summarized. In Group B 15 patients with a mean age of 47±22 years, a mean TBSA of 30±13%, and a mean ABSI score of 8.1±1.7 were included. Hypernatremia occurred on day 5±1.4. There was no significant difference between both groups for fluid resuscitation amount within the first 24 hours . Statistical analysis of the first 7 days after burn injury showed a significantly higher percentage of removed fluid in Group B for day 3, day 4, day 5, day 6 and day 7. Conclusions: Amount and velocity of fluid removal regimen after burn injury can provoke electrolyte disorders. Serum sodium concentration can be used to calculate need of fluid resuscitation for fluid maintenance. There is a need of an established fluid removal strategy., Einführung: Ausgedehnte Brandverletzungen gehen mit einem Verlust der zellulären Integrität einher. Das während dieser Phase infundierte Volumen muss, nach Wiedererlangen der zellulären Integrität, dem Brandverletzen partiell wieder entzogen werden. Dies kann Elektrolytdysregulationen provozieren. Fragestellung: Es wurde untersucht, ob ein Zusammenhang zwischen der Intensivität des Volumenentzuges und der Serum-Natrium-Konzentration festzustellen ist.Methoden: Retrospektive Studie an Schwerbrandverletzten. Es erfolgte eine Aufteilung der Patienten in normonatriäm (Gruppe A) und hypernatriäm (Gruppe B). Ergebnisse: Vierzig Patienten (12 Frauen; 28 Männer) mit einem durchschnittlichen Alter von 47±19 Jahre, eine verbrannten Körperoberfläche (TBSA) von 26±12% und einem abbreviated burned severity index (ABSI) von 7,3±2 wurden analysiert. In Gruppe A (25 Patienten) wurde ein mittleres Alter von 47±18 Jahre, eine TBSA von 23±11% und ein ABSI von 6,9±2,1 berechnet. In Gruppe B (15 Patienten) lag ein durchschnittliches Alter von 47±22 Jahren, eine TBSA von 30±13% und ein abbreviated burned severity index (ABSI) von 8,1±1,7 vor. Eine Hypernatriämie trat am 5.±1,4 Tag auf. Es zeigte sich keine signifikant unterschiedliche Volumentherapie während der ersten 24 Stunden nach dem thermalen Trauma. Die statistische Analyse der ersten 7 Tage nach der Brandverletzung zeigte signifikant höhere Volumenentzüge in Gruppe B für die Tage 3, 4, 5, 6 und 7. Schlussfolgerung: Ein kalkulierter Volumenentzug nach ausgedehnten Brandverletzungen kann eine Serum-Natrium-Dysregulation vermeiden. Die Serum-Natrium-Konzentration kann einen Beitrag zur Kalkulation des individuellen Volumenstatus nach Brandverletzungen leisten.

Diuresis following blood-gorging in Rhodnius prolixus is the major process leading to the transmission of Chagas disease. We have cloned the cDNA of the first receptor known to be involved in an antidiuretic strategy in insects, a strategy that prevents diuresis. This receptor belongs to the insect CAPA receptor family known in other insects to be activated by peptides encoded within the capability gene. We characterize the expression profile in fifthinstars and find expression is localized to the alimentary canal. Highest transcript levels are found in Malpighian tubules and the anterior midgut, which are known targets of the antidiuretic hormone, RhoprCAPA- 2., Published in PNAS, v107 n22 p10290-10295, June 1, 2010.

The insect kinins are multifunctional neuropeptides found in a variety of arthropod species, including the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae). A series of biostable insect kinin analogs based on the shared C-terminal pentapeptide core region were fed in solutions of artificial diet to the pea aphid over a period of 3 days and evaluated for antifeedant and aphicidal activity. The analogs contained either alpha,alpha-disubstituted or beta-amino acids in key positions to enhance resistance to tissue-bound peptidases and retain activity in a number of insect kinin bioassays and/or on expressed receptors. Three of the biostable analogs demonstrated antifeedant activity, with a marked reduction in honeydew formation observed after 1 day, and very high mortality. In contrast, an unmodified, parent insect kinin and two other analogs containing some of the same structural components that promote biostability are inactive. The most active analog, double Aib analog K-Aib-1 ([Aib]FF[Aib]WGa), featured aphicidal activity calculated at an LC50 of 0.063 nmol/ml (0.048 mg/ml) and an LT50 of 1.68 days, matching the potency of some commercially available aphicides. The mechanism of this activity has yet to be established. The aphicidal activity of the biostable insect kinin analogs may result from different potential mechanisms as disruption of digestive processes by interfering with gut motility patterns, digestive enzyme release and/or with fluid cycling in the gut, and also nutrient transport across the gut itself; all processes shown to be regulated by the insect kinins in other insects. However the mechanism(s) is(are) not yet known. The active insect kinin analogs represent potential leads in the development of selective environmentally friendly pest aphid control agents., Published in Peptides, v31 p498 505, 2010.

ObjectiveThe efficacy of liraglutide, a human glucagon-like peptide-1 (GLP-1) analog, to prevent or delay diabetes in UCD-T2DM rats, a model of polygenic obese type 2 diabetes, was investigated.Research design and methodsAt 2 months of age, male rats were divided into three groups: control, food-restricted, and liraglutide. Animals received liraglutide (0.2 mg/kg s.c.) or vehicle injections twice daily. Restricted rats were food restricted to equalize body weights to liraglutide-treated rats. Half of the animals were followed until diabetes onset, whereas the other half of the animals were killed at 6.5 months of age for tissue collection.ResultsBefore diabetes onset energy intake, body weight, adiposity, and liver triglyceride content were higher in control animals compared with restricted and liraglutide-treated rats. Energy-restricted animals had lower food intake than liraglutide-treated animals to maintain the same body weights, suggesting that liraglutide increases energy expenditure. Liraglutide treatment delayed diabetes onset by 4.1 ± 0.8 months compared with control (P < 0.0001) and by 1.3 ± 0.8 months compared with restricted animals (P < 0.05). Up to 6 months of age, energy restriction and liraglutide treatment lowered fasting plasma glucose and A1C concentrations compared with control animals. In contrast, liraglutide-treated animals exhibited lower fasting plasma insulin, glucagon, and triglycerides compared with both control and restricted animals. Furthermore, energy-restricted and liraglutide-treated animals exhibited more normal islet morphology.ConclusionsLiraglutide treatment delays the development of diabetes in UCD-T2DM rats by reducing energy intake and body weight, and by improving insulin sensitivity, improving lipid profiles, and maintaining islet morphology.

A simple method has been recently proposed to assess acute hydration status in humans; however, several questions remain regarding its reliability, validity, and practicality. Objective: Establish reliability of a simple method to assess euhydration, that is, to analyze whether this method can be used as a consistent indicator of a person´s hydration status. In addition, the study sought to assess the effect exercise has on urine volume when euhydration is maintained and a standardized volume of water is ingested. Methods: Five healthy physically active men and five healthy physically active women, 22.5 ± 2.3 years of age (mean ± standard deviation) reported to the laboratory after fasting for 10 hours or more on three occasions, each one week apart. During the two identical resting euhydration conditions (EuA and EuB), participants remained seated for 45 minutes. During the exercise condition (EuExer), participants exercised intermittently in an environmental chamber (average temperature and relative humidity = 32 ± 3°C and 65 ± 7%, respectively) for a period of 45 minutes and drank water to offset loss due to sweating. The order of treatments was randomized. Upon finishing the treatment period, they ingested a volume of water equivalent to 1.43% body mass (BM) within 30 minutes. Urine was collected and measured henceforth every 30 minutes for 3 hours. Results: Urine volume eliminated during EuExer (1205 ± 399.5 ml) was not different from EuB (1072.2±413.1 ml) or EuA (1068 ± 382.87 ml) (p-value = 0.44). Both resting conditions were practically identical (p-value = 0.98) and presented a strong intraclass correlation (r = 0.849, p-value = 0.001). Conclusions: This method, besides simple, proved to be consistent in all conditions; therefore, it can be used with the certainty that measurements are valid and reliable., Recientemente se ha propuesto un método sencillo para evaluar el estado agudo de hidratación en humanos, pero persisten varias preguntas con respecto a su confiabilidad, validez y utilidad práctica. Objetivo: establecer la confiabilidad de un método simple para comprobar euhidratación, es decir, evaluar si este método puede ser usado como un indicador consistente del estado de hidratación de una persona. Además, se buscaba evaluar el efecto que tiene el ejercicio sobre la producción de orina, cuando se mantiene el estado de euhidratación y se ingiere un volumen estandarizado de agua. Métodos: cinco hombres y cinco mujeres saludables y físicamente activos, con 22,5 ± 2,3 años (media ± desviación estándar), se presentaron al laboratorio después de un ayuno de 10 horas o más; en tres ocasiones, separadas por una semana de tiempo. En las dos condiciones idénticas de reposo (EuA y EuB), permanecieron sentados durante 45 minutos. En la condición de ejercicio (EuEjer) realizaron ejercicio intermitentemente en una cámara de clima controlado (temperatura media y humedad relativa = 32 ± 3° C y 65 ± 7%, respectivamente) por un lapso de 45 minutos, bebiendo agua para reponer las pérdidas por sudoración. El orden de los tratamientos fue aleatorio. Al terminar el tratamiento ingirieron un volumen de agua equivalente a 1,43% masa corporal (MC) en 30 minutos, y se recogieron y midieron los volúmenes de orina eliminados posteriormente cada 30 minutos durante 3 horas. Resultados: El volumen de orina eliminado para la condición EuEjer (1205 ± 399.5 mL) no fue diferente de EuB (1072.2±413.1 mL) ni de EuA (1068 ± 382.87mL) (p= 0.44); las dos condiciones de reposo fueron prácticamente idénticas (p = 0,98), y presentaron una correlación intraclase fuerte (r = 0.849, p = 0.001). Conclusiones: Este método, además de simple, demostró ser consistente en sus mediciones, por lo que puede ser utilizado con la certeza de que las mediciones son válidas y confiables.

The multifunctional arthropod insect kinins share the evolutionarily conserved C-terminal pentapeptide motif Phe-X1-X2-Trp-Gly-NH2, where X1 = His, Asn, Ser, or Tyr and X2 = Ser, Pro, or Ala. Insect kinins regulate diuresis in many species of insects. Compounds with similar biological activity could be exploited for the control of arthropod pest populations such as the mosquito Aedes aegypti (L.) and the southern cattle tick Rhipicephalus (Boophilus) microplus (Canestrini), vectors of human and animal pathogens, respectively. Insect kinins, however, are susceptible to fast enzymatic degradation by endogenous peptidases that severely limit their use as tools for pest control or for endocrinological studies. To enhance resistance to peptidases, analogs of the insect kinins incorporating bulky a,a-disubstituted amino acids in positions adjacent to both primary and secondary peptidase hydrolysis sites were synthesized. In comparison with a control insect kinin, several of these analogs are highly stable to hydrolysis by degradative enzymes ANCE, neprilysin and Leucine aminopeptidase. Six analogs were evaluated by calcium bioluminescence assay on recombinant receptors from mosquito and tick. Four of these analogs either matched or exceeded the potency of the control kinin peptide agonist. One of these was about 5-fold more potent than the control agonist on the tick receptor. This analog was 8-fold more potent than the control agonist on the mosquito receptor, and twice more potent than the endogenous Aedes kinin-II. The analog also demonstrated potent activity in an in vitro Aedes Malpighian tubule fluid secretion assay. Similar comparisons of analog potency cannot be made to tick kinins because no endogenous kinin has yet been identified. These potent, biostable analogs represent ideal new tools for endocrinologists studying arthropod kinin-regulated processes in vivo, particularly for ticks in which their role remains to be established., Published in General and Comparative Endocrinology, v162 p122-128, 2009. Prepared in collaboration with the Department of Entomology, Texas A&M University, College Station, the Dept of Biological Sciences, University of Leeds, UK, and the School of Biological and Chemical Sciences, Birkbeck College, University of London, UK. Sponsored in part by NATO.

MALDI-TOF/TOF tandem mass spectrometry has been applied to determine the complete sequence of a CAPA-PVK in the Gulf Coast tick, Amblyomma maculatum. Single cell analysis allowed the identification of the amino acid sequence of Ixori-PVK (PALIPFPRV-NH2), a periviscerokinin which had previously been identified from two other ticks, Ixodes ricinus and Boophilus microplus. The identification indicates greater conservation of sequence for the CAPA-PVK/CAP2b family in ticks as compared with insects. Side-chain fragmentation experiments provided data to distinguish between Leu/Ile ambiguities. The tick CAPA peptide shows a high sequence homology with other members of the insect periviscerokinin/ CAP2b peptides, which are associated with the regulation of critical physiological processes such as diuresis. Thus, the identification of this neuropeptide will provide the experimental basis to better understand regulation of water balance in these arthropods, providing a potential opportunity to develop neuropeptide-based control strategies against these livestock pests., Pub. in Pestycydy, v1-2, p67-73, 2008. ISSN 0208-8703.

With diabetes mellitus, the ability of the kidneys to maintain fluid balance is affected. Hyperglycaemia increases production of hyaluronan in cultured kidney cells implying that diabetes promotes induction of hyaluronan in the kidney. The aim of the present study was to determine if the interstitial matrix component hyaluronan is differently distributed within the kidney in diabetic rats compared to non-diabetic rats. Furthermore, to test if diabetic rats are able to respond with diuresis upon a hypotonic fluid load. The normal heterogeneous intrarenal distribution of hyaluronan was confirmed in non-diabetic control rats, with 60-fold more in the papilla than in the cortex. In diabetic animals, the cortical hyaluronan was unaffected but the papillary hyaluronan content was 3-fold higher than in non-diabetic rats. This increase correlated with a more than three-fold induction of the papillary hyaluronansynthase 2 mRNA expression. In non-diabetic animals, 2 h water loading increased papillary hyaluronan (+93%) and diuresis (17-fold). In diabetic animals, baseline diuresis was 8-fold higher than in non-diabetic animals, which correlated with hyperglycaemia, glucosuria and proteinuria. Water loading in diabetic animals did not further increase papillary hyaluronan or diuresis: the urine flow rate decreased. To conclude, papillary hyaluronan is elevated in diabetic rats, which coincides with induction of hyaluronan-synthase 2 mRNA, hyperglycaemia, glucosuria, proteinuria and overt diuresis. The inability to respond to a water load with further diuresis may be related to the already elevated papillary hyaluronan and the inability to change hyaluronan during water loading.

The kidney regulates the excretion of water and electrolytes, which maintains homeostasis and enables control of arterial blood pressure. Hyaluronan, a large negatively charged interstitial glucosaminoglycan, is heterogeneously distributed within the kidney, primarily found in the medulla. Medullary hyaluronan content changes depending on the state of body hydration and plays a part in fluid regulation through its water binding and viscoelastic properties. The aim of this thesis was to provide new insight into the regulation of intrarenal hyaluronan during different states of body hydration, during completion of kidney development, and during diabetes mellitus. Dehydration reduces medullary interstitial hyaluronan in parallel with reduced hyaluronan synthase 2 gene expression and increased urinary hyaluronidase activity. Acute hydration results in an increase in medullary hyaluronan, an increase that requires nitric oxide and prostaglandins. Urinary hyaluronidase activity decreases during hydration. The elevation of hyaluronan is important for reducing water permeability of the interstitium i.e. favoring diuresis. Changes in hyaluronan concentration constitute a morphoregulatory pathway that plays a key role in nephrogenesis. The reduction in neonatal hyaluronan depended on an angiotensin II mediated process that does not appear dependent on lymph vessel formation. If angiotensin II is blocked with an ACE inhibitor, hyaluronan accumulates, which results in structural and functional abnormalities in the kidney. Renomedullary hyaluronan is elevated during uncontrolled diabetes, which coincides with induction of hyaluronan synthase 2 mRNA, hyperglycemia, glucosuria, proteinuria and overt diuresis. The levels of hyaluronan are probably at a terminus ad quem as no further response was seen during hydration. The higher interstitial expression of hyaluronan during diabetes may be involved in the progression of diabetic nephropathy. This thesis in physiology provides new me

The distal convoluted tubule (DCT) plays an essential role in the reabsorption of NaCl by the kidney, a process that can be inhibited by thiazide diuretics. Parvalbumin (PV), a Ca(2+)-binding protein that plays a role in muscle fibers and neurons, is selectively expressed in the DCT, where its role remains unknown. We therefore investigated the renal phenotype of PV knockout mice (Pvalb(-/-)) vs. wild-type (Pvalb(+/+)) littermates. PV colocalized with the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) in the early DCT. The Pvalb(-/-) mice showed increased diuresis and kaliuresis at baseline with higher aldosterone levels and lower lithium clearance. Acute furosemide administration increased diuresis and natriuresis/kaliuresis, but, surprisingly, did not increase calciuria in Pvalb(-/-) mice. NaCl supplementation of Pvalb(-/-) mice increased calciuria at baseline and after furosemide. The Pvalb(-/-) mice showed no significant diuretic response to hydrochlorothiazide, but an accentuated hypocalciuria. A decreased expression of NCC was detected in the early DCT of Pvalb(-/-) kidneys in the absence of ultrastructural and apoptotic changes. The PV-deficient mice had a positive Ca(2+) balance and increased bone mineral density. Studies in mouse DCT cells showed that endogenous NCC expression is Ca(2+)-dependent and can be modulated by the levels of PV expression. These results suggest that PV regulates the expression of NCC by modulating intracellular Ca(2+) signaling in response to ATP in DCT cells. They also provide insights into the Ca(2+)-sparing action of thiazides and the pathophysiology of distal tubulopathies.

Acute altitude exposure causes a loss of total body water and plasma volume. Glycerol ingestion has been shown to be rapidly absorbed by the intestine, leading to increases in serum osmolality, plasma osmolality, and total body water. The purpose of this study was to determine the effects of glycerol ingestion on fluid balance and cardiovascular hemodynamics at rest and during exercise during hypobaric hypoxia. Twelve men (33 ± 8 yr, 177 ± 3 cm, 75 ± 11 kg, 52 ± 10 ml O2·kg -1·min-1) each completed 4, 3.5 hr trials in a randomized design: (A) 6% carbohydrate/electrolyte drink at 1524 m, (B) 5% glycerol drink at 1524 m, (C) 6% carbohydrate/electrolyte at 3659 m, and (D) 5% glycerol at 3659 m. The 3659 m trials were 2 weeks apart. Subjects consumed 30 ml/kg lean body mass of each drink in 5 equal volumes at minutes 0, 30, 60, 90 and 120. Exercise intensity was 50% of the ventilatory threshold at 1524 m. Plasma volume change, free water clearance, osmolar clearance, and body mass change were measured every 30 min. Cardiac output was measured at min 0 and 150 during rest and cycling by CO2 rebreathing. Glycerol ingestion (GLY) resulted in significantly lower free water clearance compared to carbohydrate/electrolyte (CHO) at min 90, 120, and 150 (p < 0.05) across altitude. Osmolar clearance was significantly higher for GLY vs CHO at min 60, 90, 120, and 150 (p< 0.05). No significant differences were found for plasma volume change, stroke volume, or heart rate. The body mass change and fluid retention were significantly higher for glycerol than for carbohydrate/ electrolyte (p< 0.05). Even though a 5% glycerol solution offset the diuresis of acute hypobaric hypoxia, there did not appear to be any beneficial effects on cardiovascular hemodynamics.

The insect kinins are present in a wide variety of insects and function as potent diuretic peptides in flies. A C-terminal aldehyde insect kinin analog, Fmoc-RFFPWG-H (R-LK-CHO), demonstrates stimulation of Malpighian tubule fluid secretion in crickets, but shows inhibition of both in vitro and in vivo diuresis in the housefly. R-LK-CHO reduced the total amount of urine voided over 3 h from flies injected with 1 mL of distilled water by almost 50%. The analog not only inhibits stimulation of housefly fluid secretion by the native kinin Musdo-K, but also by thapsigargin, a SERCA inhibitor, and by ionomycin, a calcium ionophore. The activity of R-LK-CHO is selective, however, as related C-terminal aldehyde analogs do not demonstrate an inhibitory response on housefly fluid secretion. The selective inhibitory activity of R-LK-CHO on housefly tubules represents an important lead in the development of environmentally friendly insect management agents based on the insect kinins., Pub. in Peptides, v28 p146-152, 2007.

Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level. The management of patients with rhabdomyolysis includes early vigorous hydration.

SCOPUS: ar.j, info:eu-repo/semantics/published

Stevioside is present in the plant Stevia rebaudiana Bertoni (SrB). Extracts of SrB have been used for the treatment of diabetes in, for example, Brazil, although a positive effect on glucose metabolism has not been unequivocally demonstrated. We studied the acute effects of stevioside in type 2 diabetic patients. We hypothesize that supplementation with stevioside to a test meal causes a reduction in postprandial blood glucose. Twelve type 2 diabetic patients were included in an acute, paired cross-over study. A standard test meal was supplemented with either 1 g of stevioside or 1 g of maize starch (control). Blood samples were drawn at 30 minutes before and for 240 minutes after ingestion of the test meal. Compared to control, stevioside reduced the incremental area under the glucose response curve by 18% (P =.013). The insulinogenic index (AUC(i,insulin)/AUC(i,glucose)) was increased by approximately 40% by stevioside compared to control (P <.001). Stevioside tended to decrease glucagon levels, while it did not significantly alter the area under the insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide curves. In conclusion, stevioside reduces postprandial blood glucose levels in type 2 diabetic patients, indicating beneficial effects on the glucose metabolism. Stevioside may be advantageous in the treatment of type 2 diabetes.

Fluid and electrolyte balance is affected differently at different stages of alcohol use. In this study, we examine the role of vasopressin (VP), an important hormone in body fluid regulation, in the physiological response to alcohol. A transient decrease in circulating VP levels occurs immediately after acute alcohol administration, but VP levels return to baseline levels while alcohol is still present in the blood, and there is no prolonged deficiency of VP associated with blood alcohol levels. Rather, alcohol-induced changes in renal responsiveness to VP appear to be responsible for the pattern of diuresis impaired water excretion, and recovery in the different phases of alcohol exposure. Up- and down-regulation of renal VP V2 receptors involved with renal tubular water reabsorption cause differentially altered renal function in the different phases of alcohol exposure. Further, this alcohol-induced renal receptor regulation is specific to the V2 receptors in the inner medulla region of the kidney. In addition, chronic alcohol exposure disrupts the relationships between VP synthesis, brain VP Vi receptors, and blood tonicity. Thus, alcohol-induced changes in VP regulation may affect the ability to respond to physiologic stimuli. Sensitivity of the VP system is currently being further examined with salt load stimulation studies.

Manduca diuresin (MD), a 30 amino acid peptide isolated from the tobacco hornworm Manduca sexta, was found to play an important role in the regulation of water and salt balance in the insect. To facilitate studies relating to the function and structure of MD, a synthetic gene encoding MD was assembled and expressed in Escherichia coli. Using an excretion vector, expression of the MD gene in an induced transformant was detected at the transcriptional and translational levels by Northern-blot and ELISA analyses, respectively. With the use of glutathione-S-transferase as the reporter protein, MD was confirmed to be expressed in E. coli. The recombinant product was resolved by reverse-phase HPLC into three peptide groups of different retention times, which were shown by mass spectrometry to be composed of MD deletants missing various lengths of the C-terminus. Despite the deletions and the absence of an amidated C-terminus, the deletants were shown to be biologically active, suggesting the importance of the N-terminus of MD for biological activity. (C) 2003 Elsevier Science (USA). All rights reserved.

We have previously shown that after effects of short term alcohol exposure cause rats to have an increased water diuresis in response to a water load whereas after long term alcohol exposure, rats exhibit an impaired ability to excrete a water load. Our latest data indicate that in a 4-week withdrawal phase from chronic alcohol exposure, water excretion impairment begins to return towards control levels. The up- and down-regulation of renal vasopressin V2 receptors appear to be behind differentially altered renal function in different phases of alcohol exposure. Prolonged diuresis during the acute phase of alcohol exposure is associated with a decrease in V2 receptor mRNA and a down-regulation of V2 receptors. During chronic alcohol exposure, renal V2 receptor mRNA is up-regulated, indicating that increased synthesis of V2 receptors causes increased renal efficacy of vasopressin despite similar circulating vasopressin levels between alcohol-exposed and control rats. During the withdrawal phase, V2 receptor mRNA returns toward normal levels, demonstrating that chronic alcohol-induced impairment of renal water excretion is reversible. Results suggest that alcohol-induced changes in renal responsiveness to vasopressin causes the pattern of diuresis, impaired water excretion, and recovery in the different phases of alcohol exposure.

Die Anwendung von Birkenblättern (Betulae folium) erfolgt zur Durchspülung der Harnwege. In der vorliegenden Arbeit wurde die Wirkungsweise der Birkenblätter auf verschiedenen Ebenen der Phytopharmakaforschung untersucht. Zunächst wurde in-vitro die Beeinflussung der Metallopeptidasen Neutrale Endopeptidase (NEP, EC 3.4.24.11), Angiotensin-Converting-Enzym (ACE, EC 3.4.15.1) und Leucin-Aminopeptidase (LAP, EC 3.4.11.2) durch Birkenblätterextrakte, -fraktionen und reine Naturstoffe untersucht. Die Auftrennung eines Methanol- und eines Ethylacetatextraktes führte nicht zur Gewinnung einzelner, für die Gesamtwirkungen der Extrakte verantwortlicher Fraktionen bzw. Komponenten. Die Eigenschaft der Flavonoide als wirksamkeitsmitbestimmende Inhaltsstoffe konnte jedoch bestätigt werden. Ein systematisches Screening von Flavonoiden ergab u.a., dass das Ausmaß der Enzymhemmung von der Anzahl der freien phenolischen OH-Funktionen bestimmt wurde und dass Flavonoidaglyka stärker die Enzyme hemmten, als die im Pflanzenmaterial vorliegenden Glykoside (IC50 NEP: Myricetin 42 Mikromol/L, Quercetin 192 Mikromol/L). Die in der Birkenrinde vorkommenden Triterpene Betulinsäure und Betulinol wurden als starke Inhibitoren der LAP erkannt (IC50 LAP: 7,3 +/- 1,4 bzw. 8,8 +/- 1,78 Mikromol/L). In einem nächsten Abschnitt der Arbeit wurden die Absorptionseigenschaften von Hyperosid und Rutin mit einem In-vitro-Perfusionsmodell am isolierten Rattendünndarm untersucht. Sowohl Rutin als auch Hyperosid traten unverändert als Glykoside durch den Darm in das Akzeptorkompartiment über. Auch in Form eines Birkenblätterextraktes wurde Hyperosid am Rattendünndarm absorbiert, der Extrakt veränderte jedoch nicht die Absorptionsrate. Als Mechanismus wurde der passive Transport durch die Poren der Tight junctions der Dünndarmzellen angenommen. Abschließend wurde eine Pilotstudie (n=14) durchgeführt, in der das ausgeschiedene Harnvolumen nach einmaliger Einnahme eines Birkenblättertees im Vergleich zu einer, Irrigation of the urinary tract is the therapeutic indication for Birch leaf (Betulae folium). In the present thesis, effects and efficacy of Birch leaves were investigated in various fields of medicinal plant research. The effects of Birch leaf extracts, their fractions, and pure natural compounds on the metallopeptidases - Neutral Endopeptidase (NEP, EC 3.4.24.11), Angiotensin Converting Enzyme (ACE, EC 3.4.15.1), and Leucine Aminopeptidase (LAP, EC 3.4.11.2) - were investigated in vitro. Phytochemical separation of extracts obtained by methanol and ethyl acetate did not result in more active fractions compared to those of the whole extracts. The ability of flavonoids to contribute to the efficacy reached by Birch leaf extracts, could be confirmed. A systematic screening could show that the inhibitory potency of flavonoids is dependent on the number of phenolic hydroxyl functions in their chemical structure. Aglycones of flavonoids were more active than their corresponding glycosides occurring in the plant material (IC50 NEP: myricetin 42 mikromol/L, quercetin 192 mikromol/L). Betulinic acid and betulinol, triterpenes of the bark of Betula, inhibited LAP strongly by reaching an IC50 of 7,3 +/- 1,4 mikromol/L and 8,8 +/- 1,78 mikromol/L, respectively. Furthermore, this thesis showed the absorption profiles of hyperoside and rutin in an isolated small intestine model of the rat. Both glycosides were detected in the acceptor compartment without being metabolised. Administration of hyperoside by a Birch leaf extract did not influence the absorption rate. A passive transport through the pores of the tight junctions, localized between the intestinal cells, was considered to be the mechanism of absorption of the flavonol glycosides. Finally, a human pilot study (n=14) was carried out. The excreted urinary volume was determined after a single intake of a Birch leaf infusion or tap water. An increased urine output after 4 hours of the test period was found in 50% of the vo

The purpose of the present study was to assess the suitability of roselle tea (Hibiscus Sabdariffa L.) for post-exercise rehydration, compared with pure water and a sports drink. Roselle tea is a beverage widely consumed in Mexico and highly regarded because of its purported diuretic properties. Sixteen physically active male students from the University of Costa Rica, aged 17 to 23 years old, drank each one of the three treatments on different days, the same day of the week, in random order. They arrived in the laboratory euhydrated and, after a standardized breakfast and a brief rest, exercised intermittently on a stationary bicycle in a climate-controlled room (30-35°C and 85% RH) until reaching 2.3% body mass loss dehydration. After a 30-min rest at room temperature, they drank a volume equivalent to 150% of their body mass loss of the drink assigned to that day, within 45 minutes. At the end of rehydration (0 min) urine collection was performed and repeated every 30 min for a total of 3 hours. Each sample was measured for volume, color and density. Sample volumes were analyzed as percentage of ingested fluid. Data were analyzed with descriptive statistics and two-way ANOVAs (repeated measures on both factors). While there were no statistically significant differences in total urine output (p = 0.084), an interaction was found between urine output, density, and color, with time (p < 0.001). Post-hoc analysis showed urine output to be higher initially with the sports drink, but it was significantly lower at time points 150 and 180 min. In addition, urine was significantly darker and denser at 0, 150, and 180 min with this drink, suggesting greater fluid conservation. From the results it is possible to conclude that roselle tea did not show a diuretic effect 3 hours after consumption, in exercise-dehydrated subjects. While it seems like rehydration is almost identical with the three drinks, urine composition and output dynamics is different with each beverage. I, El propósito del presente estudio fue determinar si el agua de jamaica (Hibiscus Sabdarifa L.), bebida muy consumida en México y considerada útil por su 'propiedad diurética', es adecuada para la rehidratación después del ejercicio, comparándola con una bebida deportiva y el agua pura. En este estudio participaron 16 varones, entre los 17 y 23 años de edad, físicamente activos y estudiantes de la Universidad de Costa Rica. Los sujetos consumieron los tres tratamientos en tres días distintos, el mismo día de la semana. El orden de los tratamientos fue aleatorizado. Los participantes se presentaron a cada prueba en un estado adecuado de hidratación y después de un desayuno estandarizado y un breve descanso, realizaron un ejercicio intermitente en bicicleta dentro de un cuarto de clima controlado (30-35°C y 85% HR) hasta alcanzar un 2.3% de pérdida de masa corporal. Después de descansar durante 30 min a temperatura ambiente consumieron el 150% de la pérdida de masa corporal de la bebida correspondiente a cada día, durante un período de 45 min. Al término del período de rehidratación (0 min) se inició la recolección de muestras de orina y se continuó cada 30 min hasta completar 3 horas. Se determinó el volumen, la densidady el color de cada una de las muestras. Los resultados de volumen se analizaron como el porcentaje del volumen ingerido. Para analizar los datos se utilizó estadística descriptiva y ANOVA de 2 vías de medidas repetidas en ambos factores. Aunque no hubo diferencias estadísticamente significativas en la producción total de orina (p = 0.084), se encontró una interacción entre la producción de orina, la densidad y el color, con el tiempo (p < 0.001). Al analizar estas interacciones, se observó que aunque en un inicio se excretó en mayor proporción, la producción de orina con la bebida deportiva fue significativamente menor a los 150 y180 min, además de que las orinas producidas por esta bebida fueron significativamente más densas y más oscuras a los 0, 150

Despite evidence of impaired renal fluid handling, hyponatremia, and water retention in chronic alcohol exposure and during withdrawal, the renal mechanisms involved and the role of altered vasopressin action in the kidney have not been elucidated. We have shown that the efficacy of endogenous vasopressin on the kidney and resultant changes in renal water excretion is differentially altered in the different phases of alcohol exposure. Rats acutely exposed to alcohol exhibit an increased water diuresis in response to a water load whereas rats chronically exposed to alcohol exhibit an impaired ability to excrete a water load. We have %further demonstrated that this impaired ability to excrete a water load in chronic alcohol exposure occurs under conditions of an increased renal sensitivity to vasopressin as demonstrated by suppressed diuretic efficacy of a V2 antagonist. Thus, our results to date have provided evidence of water imbalance with alcohol exposure that is likely due to altered function or numbers of vasopressin receptors, specifically renal V2 receptors, involved with tubular water reabsorption. Additionally, preliminary examination of the relationship between vasopressin pituitary and blood content indicates there is an uncoupling of the regulation of vasopressin release and circulating levels with alcohol exposure.

The hypotensive effects of the water extract of Marrubium vulgare L. and Foeniculum vulgare L. were investigated in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY). Oral administration of Marrubium or Foeniculum extract lowered the systolic blood pressure of SHR but not of WKY. In SHR, Foeniculum but not Marrubium treatment increased water, sodium and potassium excretion. Ex vivo as well as in vitro. Marrubium extract inhibited the contractile responses of rat aorta to noradrenaline and to KCl (100 mM). Inhibition was greater in aorta from SHR compared to WKY and was not affected by the NO synthase inhibitor N-nitro-L-arginine. Vascular effects of Foeniculum extract were less pronounced than those of Marrubium and were blocked by N-nitro-L-arginine. These results indicate that hypotensive activity of Marrubium and Foeniculum extracts seems to be mediated through different pathways: Foeniculum appeared to act mainly as a diuretic and a natriuretic while Marrubium displayed vascular relaxant activity.

Results from space have been unexpected and not predictable from the results of ground-based simulations. Therefore, the concept of how weightlessness and gravity modulates the regulation of body fluids must be revised and a new simulation model developed. The main questions to ask in the future are the following: Does weightlessness induce a diuresis and natriuresis during the initial hours of space flight leading to an extracellular and intravascular fluid volume deficit? Can sodium in excess be stored in a hitherto unknown way, particularly during space flight? Why are fluid and sodium retaining systems activated by spaceflight? Why are the renal responses to saline and water stimuli in space attenuated compared with those of ground simulations? How can the effects of weightlessness on fluid and electrolyte regulation be correctly simulated on the ground? The information obtained from space may be of relevance to fluid and electrolyte balance in edematous patients.

We have previously shown that fluid balances and body fluid regulation in microgravity (microG) differ from those on Earth (Drummer et al, Eur J Physiol 441:R66-R72, 2000). Arriving in microG leads to a redistribution of body fluid-composed of a shift of fluid to the upper part of the body and an exaggerated extravasation very early in-flight. The mechanisms for the increased vascular permeability are not known. Evaporation, oral hydration, and urinary fluid excretion, the major components of water balance, are generally diminished during space flight compared with conditions on Earth. Nevertheless, cumulative water balance and total body water content are stable during flight if hydration, nutritional energy supply, and protection of muscle mass are at an acceptable level. Recent water balance data disclose that the phenomenon of an absolute water loss during space flight, which has often been reported in the past, is not a consequence of the variable microG. The handling of sodium, however, is considerably affected by microG. Sodium-retaining endocrine systems, such as renin-aldosterone and catecholamines, are much more activated during microG than on Earth. Despite a comparable oral sodium supply, urinary sodium excretion is diminished and a considerable amount of sodium is retained-without accumulating in the intravascular space. An enormous storage capacity for sodium in the extravascular space and a mechanism that allows the dissociation between water and sodium handling likely contribute to the fluid balance adaptation in weightlessness.

According to a classic hypothesis, weightlessness should promote the renal excretion rate of sodium and water and lead to a fluid- and electrolyte-depleted state. This hypothesis is based on experiments in which weightlessness has been simulated in humans by head-down bed rest and water immersion. However, after 5 to 6 days of space mission, the diuretic and natriuretic responses to an intravenous isotonic saline load were attenuated and plasma norepinephrine and renin concentrations increased compared with those of the acute supine position before flight. Renal fluid excretion after an oral water load was also attenuated in space. Similar decreases were not observed during head-down bed rest. Sympathetic activity is of major importance in regulating blood volume and renal function. Studies in space have indicated that, compared with that while in a supine position on Earth, sympathoadrenal activity is increased during space flights as measured using plasma concentration and urinary excretion of norepinephrine and epinephrine. The space-induced activation of antinatriuretic mechanisms and sympathoadrenal activity could have been caused by early in-flight reduction in total and central blood volume. The decreased plasma volume may be explained by such factors as redistribution of plasma from the lower to the upper body (thin legs and puffy face), reduced food intake, and decreased muscle activity. The decrease in plasma volume and the subsequent increase in sympathetic activity is due, at least in part, to the abrupt cessation of activity in large muscle groups during microgravity, which normally counteracts the effects of gravity in the upright posture. This would lead to accumulation of albumin and fluid in the interstitial space.