Leptospirosis is a public health problem worldwide. Severe leptospirosis manifests as pulmonary edema leading to acute respiratory distress syndrome and polyuric acute renal failure (ARF). The etiology of leptospirosis-induced pulmonary edema is unclear. Lung edema clearance is largely affected by active sodium transport out of the alveoli rather than by reversal of the Starling forces. The objective of this study was to profile leptospirosis-induced ARF and pulmonary edema. We inoculated hamsters with leptospires and collected 24-h urine samples on postinoculation day 4. On day 5, the animals were killed, whole blood was collected, and the kidneys and lungs were removed. Immunoblotting was used to determine expression and abundance of water and sodium transporters. Leptospirosis-induced ARF resulted in natriuresis, lower creatinine clearance, and impaired urinary concentrating ability. Renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2 was lower in infected animals, whereas that of the Na-K-2Cl cotransporter NKCC2 was higher. Leptospirosis-induced lesions, predominantly in the proximal tubule, were responsible for the polyuria and natriuresis observed. The polyuria might also be attributed to reduced aquaporin 2 expression and the attendant urinary concentrating defect. In the lungs, expression of the epithelial sodium channel was lower, and NKCC1 expression was upregulated. We found that leptospirosis profoundly influences the sodium transport capacity of alveolar epithelial cells and that impaired pulmonary fluid handling can impair pulmonary function, increasing the chance of lung injury. Greater knowledge regarding sodium transporter dysregulation in the lungs and kidneys can provide new perspectives on leptospirosis treatment.

Magnesium is a potent vasodilator whose effects have not been evaluated in renal ischemia. The antioxidant properties of N-acetylcysteine (NAC) partially protect animals from ischemic/reperfusion injury. This study was designed to evaluate magnesium supplementation, alone or combined with NAC, on ischemic acute renal failure. Rats were maintained on normal diets, supplemented or not with MgCl 2 ⅐6H 2 O (1% in drinking water) for 23 d, and some rats received NAC (440 mg/kg body wt) on days 20 to 23. On day 21, ischemia was induced by clamping both renal arteries for 30 min. Five groups were studied: Normal, ischemia, ischemia؉magnesium, ischemia؉NAC, and ischemia؉magnesium؉NAC. GFR (inulin clearance), renal blood flow (RBF), FEH 2 O, and FENa were determined. Serum magnesium was decreased in ischemia-only rats. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. However, NAC completely restored the tubular damage induced by ischemia/reperfusion. Semiquantitative immunoblotting showed that NAC prevented the decreased expression of Na-K-2Cl co-transporter and aquaporin 2 after renal ischemia/reperfusion. Untreated rats with acute renal failure demonstrated markedly decreased endothelial nitric oxide synthase expression. Significantly, treatment with NAC, magnesium, or both completely inhibited downregulation of endothelial nitric oxide synthase. The tubular necrosis scores were lower in rats that were treated with NAC alone or with the magnesium-NAC combination. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. The NAC protected tubules from ischemia, decreased infiltrating macrophages/lymphocytes, and had a mild protective effect on GFR. In ischemic/reperfusion injury, renal function benefits more from the magnesium-NAC combination than from magnesium alone.

It is well-known that glucagon increases fractional excretion of urea in rats after a protein intravenous infusion. This effect was investigated by using: (a) in vitro microperfusion technique to measure [(14)C]-urea permeability (Pu x 10(-5)cm/s) in inner medullary collecting ducts (IMCD) from normal rats in the presence of 10(-7)M of glucagon and in the absence of vasopressin and (b) immunoblot techniques to determine urea transporter expression in tubule suspension incubated with the same glucagon concentration. Seven groups of IMCDs (n = 47) were studied. Our results revealed that: (a) glucagon decreased urea reabsorption dose-dependently; (b) the glucagon antagonist des-His(1)-[Glu(9)], blocked the glucagon action but not vasopressin action; (c) the phorbol myristate acetate, decreased urea reabsorption but (d) staurosporin, restored its effect; e) staurosporin decreased glucagon action, and finally, (f) glucagon decreased UT-A1 expression. We can conclude that glucagon reduces UT-A1 expression via a glucagon receptor by stimulating PKC.

LC, Magaldi AJ. Aquaporin 2 expression increased by glucagon in normal rat inner medullary collecting ducts. Am J Physiol Renal Physiol 296: F54 -F59, 2009. First published October 1, 2008 doi:10.1152/ajprenal.90367.2008.-It is well known that Glucagon (Gl) is released after a high protein diet and participates in water excretion by the kidney, principally after a protein meal. To study this effect in in vitro perfused inner medullary collecting ducts (IMCD), the osmotic water permeability (Pf; m/s) at 37°C and pH 7.4 in normal rat IMCDs (n ϭ 36) perfused with Ringer/HCO 3 was determined. Gl (10 Ϫ7 M) in absence of Vasopressin (AVP) enhanced the Pf from 4.38 Ϯ 1.40 to 11.16 Ϯ 1.44 m/s (P Ͻ 0.01). Adding 10 Ϫ8 , 10 Ϫ7 , and 10 Ϫ6 M Gl, the Pf responded in a dose-dependent manner. The protein kinase A inhibitor H8 blocked the Gl effect. The specific Gl inhibitor, des-His 1 -[Glu 9 ] glucagon (10 Ϫ7 M), blocked the Glstimulated Pf but not the AVP-stimulated Pf. There occurred a partial additional effect between Gl and AVP. The cAMP level was enhanced from the control 1.24 Ϯ 0.39 to 59.70 Ϯ 15.18 fm/mg prot after Gl 10 Ϫ7 M in an IMCD cell suspension. The immunoblotting studies indicated an increase in AQP2 protein abundance of 27% (cont 100.0 Ϯ 3.9 vs. Gl 127.53; P ϭ 0.0035) in membrane fractions extracted from IMCD tubule suspension, incubated with 10 Ϫ6 M Gl. Our data showed that 1) Gl increased water absorption in a dosedependent manner; 2) the anti-Gl blocked the action of Gl but not the action of AVP; 3) Gl stimulated the cAMP generation; 4) Gl increased the AQP2 water channel protein expression, leading us to conclude that Gl controls water absorption by utilizing a Gl receptor, rather than a AVP receptor, increasing the AQP2 protein expression. glucagon; aquaporin 2; water transport; glucagon antagonist; vasopressin GLUCAGON IS A POLYPEPTIDE whose major physiological role is to participate in the regulation of blood sugar levels. Its action is mainly on hepatic glycogenolysis and gluconeogenesis. Even though the kidney is not considered to be the principal target organ for the action of glucagon, it has been known since 1957 (22) that this hormone enhances sodium excretion after intravenous administration to dogs. Other investigators have confirmed the natriuretic effect of glucagon by using different doses (9, 18, 19). In 1958, Sutherland et al. (23) showed that glucagon was able to produce glycogen breakdown in hepatocytes by stimulating adenylyl cyclase and cyclic adenosine monophosphate (cAMP).In 1976, Mulvehill et al. (15) demonstrated that glucagon produced a dose-dependent stimulation of adenylyl cyclase in cell-free preparations of human renal medullas. This finding showed that the effect of glucagon could be mediated by cAMP. In the 1980s, Bailly et al. (4), by measuring glucagonsensitive adenylyl cyclase activity, showed that distal nephrons are highly responsive to this hormone, and Butlen et al. (7), using [125 I]glucagon, showed that the nephron has a specific receptor for glucagon. On the ot...

. Today, despite advances in AA use with the development of vacuum therapy, the Bogota Stock Exchange (BB) is still widely used. In our institution and throughout Brazil, both techniques are used and the study's goal is to evaluate the morbidity and the result of the integrity of the abdominal wall after the use of both techniques. METHODS METHODS METHODS METHODS METHODSA retrospective study was conducted at HCFMUSP, identifying patients undergoing temporary abdominal closure (FAT) between January 2005 and December 2011. Data were collected through review of medical records. Data were compared in patients undergoing treatment with assisted closing the vacuum and the Bogota bag.Inclusion criteria were temporary abdominal closure indication survival and the definitive abdominal closure. FAT indications included: abdominal trauma, severe abdominal sepsis and ACS. Data collected included age, FAT indication, the number of procedures in the operating room and the primary fascial closure rate. In the postoperative period, one group of three surgeons followed all patients and performed all reoperations. As soon as possible, the aponeurosis of the edges were subjected to progressive approach with careful not to cause abdominal hypertension.The demographics of the two study groups (BB and VAC) were compared using the chi-square test of Pearson or Fisher's exact test for categorical variables and the Student t test for continuous variables. RESULTS RESULTS RESULTS RESULTS RESULTSDuring the study period, 59 patients require some kind of temporary abdominal closure (FAT), however, only 29 patients survived the final abdominal closure (52.5% mortality). One patient was excluded (subject to closure Backaus forceps). Thus, 28 patients were included, and, after two years of follow-up, none of them developed abdominal hernia or intestinal fistulas.There was no statistical difference between the study groups with respect to age (p> 0.05) and a significant difference regarding indications for temporary abdominal closure (p <0.05) ( Table 1).The primary closure rates were similar in both groups (p = 0.98). The average time (days) for fascial closure was 10.8 days for the BB group and 7.52 days in the group VAC (Table 2). DISCUSSION DISCUSSION DISCUSSION DISCUSSION DISCUSSIONIn this study, there was no statistical difference between the closing assisted vacuum and the Bogota bag (VAC and BB) when analyzed the number of operations, the primary closure, and the average time of closing. However, a previous study 19 showed better results when using VAC BB was compared on the primary closure (50 to 70 %% and 88% for BB VAC). The best approach to achieve the definitive abdominal closure in patients with open abdomen remains controversial. To improve the fascial closure rate, the excess volume resuscitation should be avoided, the water balance should be carefully implemented, not only on admission, but also throughout the course of treatment with open abdomen 20 . The high rate of primary closure found in our patients, 80% for BB and 96% f...