Acute renal failure caused by nephrotoxins.
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Renal micropuncture studies have greatly changed our views on the pathophysiology of acute renal failure caused by nephrotoxins. Formerly, this type of renal insufficiency was attributed to a direct effect of the nephrotoxins on tubule epithelial permeability. According to that theory, glomerular filtration was not greatly diminished, the filtrate formed being absorbed almost quantitatively and nonselectively across damaged tubule epithelium. Studies in a wide variety of rat models have now shown glomerular filtration to be reduced to a level which will inevitably cause renal failure in and of itself. Passive backflow of filtrate across tubular epithelium is either of minor degree or nonexistent even in models where frank tubular necrosis has occurred. This failure of filtration cannot be attributed to tubular obstruction since proximal tubule pressure is distinctly subnormal in most models studied. Instead, filtration failure appears best attributed to intrarenal hemodynamic alterations. While certain facts tend to incriminate the renin-angiotensin system as the cause of the hemodynamic aberrations, others argue to the contrary. The issue is underactive investigation. (+info)
Influence of body temperature on the development of fatigue during prolonged exercise in the heat.
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We investigated whether fatigue during prolonged exercise in uncompensable hot environments occurred at the same critical level of hyperthermia when the initial value and the rate of increase in body temperature are altered. To examine the effect of initial body temperature [esophageal temperature (Tes) = 35.9 +/- 0.2, 37.4 +/- 0. 1, or 38.2 +/- 0.1 (SE) degrees C induced by 30 min of water immersion], seven cyclists (maximal O2 uptake = 5.1 +/- 0.1 l/min) performed three randomly assigned bouts of cycle ergometer exercise (60% maximal O2 uptake) in the heat (40 degrees C) until volitional exhaustion. To determine the influence of rate of heat storage (0.10 vs. 0.05 degrees C/min induced by a water-perfused jacket), four cyclists performed two additional exercise bouts, starting with Tes of 37.0 degrees C. Despite different initial temperatures, all subjects fatigued at an identical level of hyperthermia (Tes = 40. 1-40.2 degrees C, muscle temperature = 40.7-40.9 degrees C, skin temperature = 37.0-37.2 degrees C) and cardiovascular strain (heart rate = 196-198 beats/min, cardiac output = 19.9-20.8 l/min). Time to exhaustion was inversely related to the initial body temperature: 63 +/- 3, 46 +/- 3, and 28 +/- 2 min with initial Tes of approximately 36, 37, and 38 degrees C, respectively (all P < 0.05). Similarly, with different rates of heat storage, all subjects reached exhaustion at similar Tes and muscle temperature (40.1-40.3 and 40. 7-40.9 degrees C, respectively), but with significantly different skin temperature (38.4 +/- 0.4 vs. 35.6 +/- 0.2 degrees C during high vs. low rate of heat storage, respectively, P < 0.05). Time to exhaustion was significantly shorter at the high than at the lower rate of heat storage (31 +/- 4 vs. 56 +/- 11 min, respectively, P < 0.05). Increases in heart rate and reductions in stroke volume paralleled the rise in core temperature (36-40 degrees C), with skin blood flow plateauing at Tes of approximately 38 degrees C. These results demonstrate that high internal body temperature per se causes fatigue in trained subjects during prolonged exercise in uncompensable hot environments. Furthermore, time to exhaustion in hot environments is inversely related to the initial temperature and directly related to the rate of heat storage. (+info)
Desiccation resistance in interspecific Drosophila crosses. Genetic interactions and trait correlations.
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We used crosses between two closely related Drosophila species, Drosophila serrata and D. birchii, to examine the genetic basis of desiccation resistance and correlations between resistance, physiological traits, and life-history traits. D. serrata is more resistant to desiccation than D. birchii, and this may help to explain the broader geographical range of the former species. A comparison of F2's from reciprocal crosses indicated higher resistance levels when F2's originated from D. birchii mothers compared to D. serrata mothers. However, backcrosses had a resistance level similar to that of the parental species, suggesting an interaction between X-linked effects in D. serrata that reduce resistance and autosomal effects that increase resistance. Reciprocal differences persisted in hybrid lines set up from the different reciprocal crosses and tested at later generations. Increased desiccation resistance was associated with an increased body size in two sets of hybrid lines and in half-sib groups set up from the F4's after crossing the two species, but size associations were inconsistent in the F2's. None of the crosses provided evidence for a positive association between desiccation resistance and glycogen levels, or evidence for a tradeoff between desiccation resistance and early fecundity. However, fecundity was positively correlated with body size at both the genetic and phenotypic levels. This study illustrates how interspecific crosses may provide information on genetic interactions between traits following adaptive divergence, as well as on the genetic basis of the traits. (+info)
Pilsicainide intoxication in a patient with dehydration.
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An 81-year-old woman developed pilsicainide intoxication associated with dehydration. The patient had been taking pilsicainide (100 mg/day) for 1 year because of paroxysmal atrial fibrillation. Her renal function was within normal limits. One week before admission, she was suffering from pneumonia, and had appetite loss, fever, and severe fatigue. Physical examination revealed dehydration. The electrocardiogram (ECG) on admission showed atrioventricular dissociation, idioventricular rhythm with marked QRS widening and QTc prolongation. The plasma concentration of pilsicainide on admission was markedly elevated at 6.2 microg/ml, approximately 6 times the therapeutic range (0.25-1.0 microg/ml). Continuous saline infusion was initiated for the treatment of dehydration,which progressively improved. As a result, sinus rhythm was recovered 2 h after admission, and the QRS and JT intervals gradually normalized. This is an interesting case because the proarrhythmia of pilsicainide was induced by dehydration. (+info)
Regulation of aquaporin mRNA expression in rat kidney by water intake.
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Three aquaporins (AQP) are present in the membrane of the principal collecting duct cells. On the apical side, the levels of AQP2 protein are increased in response to both arginine vasopressin and water deprivation. However, whether this change parallels changes in the abundance of AQP3 and AQP4 in the basolateral membrane is less well known. This study evaluates the effect of either dehydration or water loading on the rat kidney mRNA expression of AQP2, AQP3, and AQP4. Poly(A+)RNA was prepared from renal cortex and medulla of control, water-deprived, well hydrated, and water-deprived rats treated with OPC31260, a V2 receptor antagonist. Northern blots were done and mRNA levels were quantified using a PhosphorImager system. Relative to control, water deprivation increased the expression of cortical AQP2, -3, and -4, whereas water loading decreased the cortical and medullar expression of AQP2, -3, and -4. Therefore, in addition to AQP2 and -3, AQP4 expression is also regulated by water intake. Treatment with OPC31260 (40 mg/kg of weight per d) inhibited up to 20 to 30% the upregulation of AQP-mRNA induced by water deprivation. Blood values of arginine vasopressin and aldosterone were significantly increased by water deprivation, whereas they were unchanged by water overloading. Taken together, these results indicate that renal AQP2, -3, and -4 expression is regulated in a coordinated manner. Simultaneous up- or downregulation of the three transcripts occurred upon either water deprivation or water loading of animals, respectively. However, the signaling mechanism for the two long-term adaptive processes may be different, and, in addition to arginine vasopressin, other factors may be involved in the transcriptional regulatory processes. (+info)
Thermal dehydration-induced thirst in spontaneously hypertensive rats.
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Spontaneously hypertensive (SH) rats and normotensive Wistar-Kyoto (WKY) rats were exposed to either 25 or 37.5 degrees C for 3.5 h, and their thermal and water balance responses were compared. After exposure, either a blood sample was obtained or the rats were allowed to rehydrate for 4 h. SH rats had both higher core temperatures and evaporative water losses during heat exposure. Measurements of hematocrit, hemoglobin concentration, plasma protein and sodium concentrations, and plasma osmolality indirectly showed that the SH rats were dehydrated relative to the WKY rats after exposure to either 25 or 37.5 degrees C. SH rats drank significantly more water but also had significantly higher urine volumes than the WKY rats and thus rehydrated only slightly better than the WKY rats. SH and WKY rats had similar levels of water intake and urine output after 24 h of water deprivation. The elevated thermal response of SH rats to heat exposure does not appear to lead to uncompensatable changes in body water status. (+info)
Cardiovascular changes associated with dehydration and drinking in unrestrained, lactating goats.
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The aim of this study was to investigate if the alertness connected with seeing water increased arterial blood pressure and heart rate to the same extent as the act of drinking, and if ingestion of warm water caused a different effect compared with ingestion of cool water on these cardiovascular variables. Seven goats of the Swedish domestic breed (Capra hircus) were used in a cross-over design. The animals were dehydrated for 24 h. They were allowed to watch water being prepared for 11-16 min, after which they were given access to warm (35 degrees C) or cool (15 degrees C) water. The goats drank 6.86 +/- 0.36 l of the warm water and 4.54 +/- 0.35 l of the cool water (P < 0.05) within the first hour. The arterial blood pressure, heart rate and activity of the animals were registered by an implanted telemetric device. Dehydration did not affect the cardiovascular variables, except before feeding in the morning, when the heart rate accelerated faster in dehydrated goats. Heart rate increased abruptly when dehydrated goats saw water being prepared, remained at the increased level during drinking and then slowly declined. It increased again during the afternoon feeding, to a level similar to that on control days, but between 18.00 and 06.00 h the heart rate was higher than during control nights. Blood pressure did not change when the goats saw water, but increased when they drank. On the morning following rehydration, the rise in heart rate in response to feeding was delayed compared with that during control and dehydration periods. It is concluded that seeing water caused arousal in the goats, resulting in an accelerated heart rate. The additional rise in blood pressure during the act of drinking appears to be a combination of excitement and sensory inputs from the pharyngeal region, causing a temporary activation of the sympathetic nervous system. (+info)
The mouse as a model to study adhesion formation following endoscopic surgery: a preliminary report.
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Our aim was to investigate the feasibility of a mouse model to study adhesion formation following endoscopic surgery. Following preliminary studies to establish anaesthesia and pneumoperitoneum pressure, a prospective randomized study was carried out to investigate the effect of CO2 pneumoperitoneum on postoperative adhesions. In group I (control group), the duration of pneumoperitoneum was shorter than 5 min. In groups II, III and IV, pneumoperitoneum was maintained for 60 min without flow, with a continuous low flow (1 ml/min) and a continuous high flow (10 ml/min) through the abdominal cavities of the mice using non-humidified CO2, respectively. Adhesions were scored after 7 days by laparotomy. The total adhesion scores were 0.9 +/- 0.8 (n = 15) in control group, 2.4 +/- 0.8 (n = 15) (P < 0.001 versus control group) in group II with no flow, 2.6 +/- 1.3 (n = 15) (P < 0.001 versus control group) in group III with a continuous low flow and 4.3 +/- 0.9 (n = 15) (P < 0.001 versus control group and P < 0.001 versus group II and III) in group IV with a continuous high flow. In conclusion, the mouse can be used as a model to study adhesion formation following endoscopic surgery. Duration of CO2 pneumoperitoneum is a co-factor in adhesion formation. (+info)