Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function.
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Acute episodes of severe renal ischemia result in acute renal failure (ARF). These episodes are followed by a characteristic recovery and repair response, whereby tubular morphology and renal function appear completely restored within approximately 1 mo. However, the chronic effects of such an injury have not been well studied. Male rats were subjected to 60-min bilateral ischemia followed by reperfusion, yielding a characteristic injury. Postischemic animals manifested severe diuresis, peaking at 1 wk postinjury (volume: >45 ml/day, ARF vs. 18 ml/day, sham; P < 0.05). Urine flow subsequently declined but remained significantly elevated vs. sham animals for a 40-wk period. The prolonged alteration in urinary concentrating ability was attributable, in part, to a diminished capacity to generate a hypertonic medullary interstitium. By week 16, proteinuria developed in the post-ARF group and progressed for the duration of the study. Histological examination revealed essentially normal tubular morphology at 4 and 8 wk postinjury but the development of tubulointerstitial fibrosis at 40 wk. Transforming growth factor (TGF)-beta1 expression was elevated at 40 wk, but not at 4 and 8 wk postinjury. Microfil analysis revealed an approximately 30-50% reduction in peritubular capillary density in the inner stripe of the outer medulla at 4, 8, and 40 wk in post-ARF groups vs. sham animals. In addition, post-ARF rats manifested a significant pressor response to a low dose of ANG II (15 ng x kg(-1) x min(-1)). We hypothesize that severe ischemic injury results in a permanent alteration of renal capillary density, contributing to a urinary concentrating defect and the predisposition toward the development of renal fibrosis. (+info)
Water acquisition and partitioning in Drosophila melanogaster: effects of selection for desiccation-resistance.
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We examined physiological features related to water balance in five replicate populations of Drosophila melanogaster that have undergone selection for enhanced resistance to desiccation (D populations) and in five replicate control (C) populations. Adult D flies contain 34 % more water than the control flies. We examined two hypotheses for increased water acquisition in the D flies: (i) that they accumulate more water early in development and (ii) that they have a reduced post-eclosion diuretic water loss. We found no evidence of differential water or dry mass acquisition between the C and D populations prior to adulthood. We also found no evidence of differential post-eclosion diuresis, i.e. both C and D groups showed insignificant changes in water volume in the 4 h period immediately after eclosion. In addition, we quantified water content in the intra- and extracellular compartments of the C and D populations and were able to identify the hemolymph as the primary storage site of the 'extra' water carried by the desiccation-resistant flies. We estimated that 68 % of the increased water volume observed in the D flies was contained in the hemolymph. Desiccation-resistance was strongly correlated with hemolymph volume and only weakly with intracellular water volume. Survival during desiccation was also strongly related to the carbohydrate content of the D flies. It has been presumed that the D flies accumulate carbohydrate primarily as intracellular glycogen, which would result in a significant increase in intracellular water volume. We found that carbohydrate content was weakly correlated with intracellular water volume and more strongly with hemolymph volume. The carbohydrate pool in the D flies may, therefore, be contained in the extracellular compartment as well as in cells. These results are suggestive of the importance of modifications in hemolymph volume and hemolymph solute concentrations in the evolution of enhanced desiccation-tolerance in populations of Drosophila melanogaster. (+info)
Hydration status affects nuclear distribution of transcription factor tonicity responsive enhancer binding protein in rat kidney.
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Tonicity responsive enhancer binding protein (TonEBP) is the transcription factor that regulates tonicity responsive expression of proteins that catalyze cellular accumulation of compatible osmolytes. In cultured MDCK cells, hypertonicity stimulates the activity of TonEBP via a combination of increased protein abundance and increased nuclear localization. For investigating regulation of TonEBP in the kidney, rats were subjected to water loading or dehydration. Water loading lowered urine osmolality and mRNA expression of sodium/myo-inositol cotransporter (SMIT), a target gene of TonEBP, in the renal medulla; dehydration doubled the urine osmolality and increased SMIT mRNA expression. In contrast, overall abundance of TonEBP and its mRNA measured by immunoblot and ribonuclease protection assay, respectively, was not affected. Immunohistochemical analysis, however, revealed that nuclear distribution of TonEBP is generally increased throughout the medulla in dehydrated animals compared with water loaded animals. Increased nuclear localization was particularly dramatic in thin limbs. Notable exceptions were the middle to terminal portions of the inner medullary collecting ducts and blood vessels, where a change in TonEBP distribution was not evident. Immunohistochemical detection of SMIT mRNA revealed that the changes in nuclear distribution of TonEBP correlate with expression of SMIT. It is concluded that under physiologic conditions, nucleocytoplasmic distribution is the dominant mode of regulation of TonEBP in the renal medulla. (+info)
Matching spiracle opening to metabolic need during flight in Drosophila.
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The respiratory exchange system of insects must maximize the flux of respiratory gases through the spiracles of the tracheal system while minimizing water loss. This trade-off between gas exchange and water loss becomes crucial when locomotor activity is increased during flight and metabolic needs are greatest. Insects that keep their spiracles mostly closed during flight reduce water loss but limit the flux of oxygen and carbon dioxide into and out of the tracheal system and thus attenuate locomotor performance. Insects that keep their spiracles completely open allow maximum gas exchange but face desiccation stress more quickly. Experiments in which water vapor was used as a tracer gas to track changes in the conductance of the respiratory system indicated that flying fruit flies minimize potential water loss by matching the area of the open spiracles to their gas exchange required for metabolic needs. This behavior maintained approximately constant pressure for carbon dioxide (1.35 kilopascals) and oxygen (19.9 kilopascals) within the tracheal system while reducing respirometric water loss by up to 23% compared with a strategy in which the spiracles are held wide open during flight. The adaptive spiracle-closing behavior in fruit flies has general implications for the ecology of flying insects because it shows how these animals may cope with environmental challenges during high locomotor performance. (+info)
Osmolar relation between cerebrospinal fluid and serum in hyperosmolar hypernatraemic dehydration.
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The relation between cerebrospinal fluid (CSF) and serum osmolality was studied in 16 patients with hyperosmolar hypernatraemic dehydration before treatment. After correcting shock and acidosis, 0-45% saline in 2-5 or 5% dextrose was infused in each patient over a 48- to 72-hour period. During rehydration, serum osmolality, electrolyte concentrations, urea nitrogen, and blood pH were measured sequentially. Five patients developed severe neurological abnormalities within 48 hours of addmission (convulsions 2, convulsions with hemiplegia 2, hemiplegia 1). Of these, 3 had residual defects on follow-up at least one year later. This group was indistinguishable from the 11 without significant neurological abnormality, both on clinical grounds before rehydration, and after analysis of admission and subsequent serum biochemical variables. A significant osmolar gap (greater than 4 mmol/kg H2O) between serum and CSF was found in 13 patients. Severe neurological disturbance only occurred when CSF osmolality exceeded that of serum by 7 or more mmol/kg H2O. Discriminant analysis of the paired osmolar data showed that D = -117+1-74 X(CSF osmolality) -1-41 X (serum osmolality), and that severe neurological abnormality was predicted when D was positive. (+info)
Characterization of (2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo- 2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide (SSR149415), a selective and orally active vasopressin V1b receptor antagonist.
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(2S,4R)-1-[5-Chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo- 2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide (SSR149415), the first selective, nonpeptide vasopressin V1b receptor antagonist yet described, has been characterized in vitro and in vivo. SSR149415 showed competitive nanomolar affinity for animal and human V1b receptors and exhibited much lower affinity for rat and human V1a, V2, and oxytocin receptors. Moreover, this compound did not interact with a large number of other receptors, enzymes, or ion channels. In vitro, SSR149415 behaved as a full antagonist and potently inhibited arginine vasopressin (AVP)-induced Ca2+ increase in Chinese hamster ovary cells expressing rat or human V1b receptors. The in vivo activity of SSR149415 has been studied in several models of elevated corticotropin secretion in conscious rats. SSR149415 inhibited exogenous AVP-induced increase in plasma corticotropin, from 3 mg/kg i.p. and 10 mg/kg p.o. upwards. Similarly, this compound antagonized AVP-potentiated corticotropin release provoked by exogenous corticoliberin at 3 mg/kg p.o. The effect lasted for more than 4 h at 10 mg/kg p.o. showing a long-lasting oral effect. SSR149415 (10 mg/kg p.o.) also blocked corticotropin secretion induced by endogenous AVP increase subsequent to body water loss. Moreover, 10 mg/kg i.p SSR149415 inhibited plasma corticotropin elevation after restraint-stress in rats by 50%. In the four-plate test, a mouse model of anxiety, SSR149415 (3 mg/kg p.o. upwards) displayed anxiolytic-like activity after acute and 7-day repeated administrations. Thus, SSR149415 is a potent, selective, and orally active V1b receptor antagonist. It represents a unique tool for exploring the functional role of V1b receptors and deserves to be clinically investigated in the field of stress and anxiety. (+info)
Epidemiology of acute viral gastroenteritis in children hospitalized in Rouen, France.
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This study assessed the epidemiologic characteristics of acute viral gastroenteritis in hospitalized children. A stool sample obtained from each child was analyzed for the presence of astrovirus, calicivirus, rotavirus, adenovirus, enterovirus, and digestive bacteria. Of the 438 stool samples obtained, 138 tested positive for > or =1 pathogen during the winters of 1997-1998 and 1998-1999 (P<.001). Virologic tests revealed rotavirus in 17.3% of samples, calicivirus in 7.3%, astrovirus in 6.8%, adenovirus in 0.7%, and > or =1 virus in 5.4%. Median age was higher for patients with rotavirus gastroenteritis than it was for those with astrovirus or calicivirus gastroenteritis (P=.014). Mean duration of hospitalization was statistically significantly lower for children with rotavirus gastroenteritis (P=.022), despite the more-frequent dehydration observed among children with rotavirus versus those with astrovirus or calicivirus gastroenteritis (P=.007). In contrast, enteral rehydration was more rapidly achieved in patients with gastroenteritis due to rotavirus. (+info)
Evaluation of two intravenous rehydration solutions in cholera and non-cholera diarrhoea.
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A clinical trial was carried out with 126 male patients over 2 years of age suffering from diarrhoea requiring intravenous rehydration, 80 of the patients suffering from cholera and 46 from non-cholera diarrhoea. A new "diarrhoea treatment solution" (DTS) containing sodium at a concentration of 118 mmol/litre and glucose at 44 mmol/litre was compared with the usual Dacca intravenous solution (DS) which has a sodium concentration of 133 mmol/litre and contains no glucose. The other constituents and their concentrations were the same in both solutions. All the patients responded well clinically and made an uneventful recovery. Oral water intake measured during the first 24 h was higher in the group receiving the DS. This group also excreted a significantly higher quantity of sodium in the urine. A significant fall in the level of blood glucose from the admission values occurred in both the groups; the fall was relatively less in the DTS group, this solution containing 44 mmol of glucose per litre. Further work is required to find the optimum concentration of glucose in the solution for infants and young children. (+info)