Effect of allopurinol in the course of adriamycin induced nephropathy

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, and 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 ± 6.39 mg/24 h; NCG = 59.8 ± 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 ± 17.5 mg/24h; TNG-I = 49.1 ± 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 ± 22.23 mg/24 h ad 72.66 ± 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48% and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.

Effects of glucose infusion on the endocrine, metabolic and cardiorespiratory responses to halothane anaesthesia of ponies

Glucose was infused intravenously into six ponies during halothane anaesthesia, to evaluate its effect on their endocrine response to anaesthesia. The ponies were premedicated with acepromazine, and anaesthesia was induced with thiopentone and maintained with halothane in oxygen for two hours. Glucose was infused to maintain the plasma glucose concentration above 20 mmol/litre. Anaesthesia was associated with hypothermia, a decrease in haematocrit, hypotension, hyperoxaemia, respiratory acidosis and an increase in the plasma concentrations of lactate and arginine vasopressin. The concentration of β-endorphin in plasma increased transiently after 20 minutes but there were no changes in concentrations of adrenocorticotrophic hormone, dynorphin, cortisol or catecholamines. These data suggest that the glucose infusion attenuated the normal adrenal response of ponies to halothane anaesthesia.

Role of ticlopidine on adriamycin-induced nephropathy

The effect of ticlopidine on rats with adriamycin nephropathy was observed during 26 weeks. In the ticlopidine-treated nephrotic animals (TNG), proteinuria was less than in the untreated nephrotic animals (NG), but this difference was significant only at week 6 (TNG = 47.27 ± 16.52 versus NG = 100.08 ± 13.83 mg/24h, p < 0.01) and week 26 (TNG = 157.00 ± 28.73 versus NG = 217.00 ± 21.73 mg/24h, p< 0.01) after ADR injection. NG presented severe tubulointerstitial abnormalities with a tubulointerstitial lesion index of 3+. No difference in glomerular lesions was observed among the groups (NG median = 6%, TNG median = 4% and TCG median = 2%). The tubulointerstitial lesion index of TNG was less intense (median = 2+) but not different from those of the control groups (CG median = 1+; TCG median = 0+) nor NG (median = 3+). We concluded that the treatment with ticlopidine produced some partially beneficial effects but did not prevent the development of adriamycin-induced nephropathy.

Investigation into the use of the Laryngeal Mask Airway in pentobarbital anesthetized dogs

Objective - To investigate the use of the laryngeal mask airway (LMA) in dogs. Study Design - Prospective experimental study. Animals - Eight healthy adult mixed breed dogs weighing from 15 to 20 kg. Methods - The dogs were anesthetized with intravenous pentobarbital. An LMA was introduced after the induction of anesthesia and 1 L/min O2 plus 1 L/min air was delivered using a circle anesthetic system. Respiratory rate, tidal volume, arterial O2 saturation (pulse oximetry), end tidal CO2, inspired fraction of O2, pulse rate, and mean arterial blood pressure were measured after the insertion of the LMA and 30, 60, 90, and 120 minutes afterwards. Results - There were no changes in respiratory rate, tidal volume, arterial O2 saturation, and pulse rate during anesthesia. End tidal CO2 decreased significantly by the end of anesthesia and ventilation appeared satisfactory. Conclusions - An LMA appeared to be an alternative option to maintain the patency of the airway in dogs. Clinical Relevance - This device may allow safe maintenance of an airway in dogs when intubation is difficult or when it interferes with the procedure (eg, cervical myelography). ©Copyright 1999 by The American College of Veterinary Surgeons.

Increased natural killer activity does not prevent progression of experimental kala-azar

Kala-azar is the visceral form of leishmaniasis and it is caused by intracellular parasites from the complex Leishmania donovani. Golden hamster (Mesocricetus auratus) infected with Leishmania donovani develop a disease very similar to human Kala-azar. There is conspicuous hipergammaglobulinaemia and their T cells do not respond to stimulation with parasite antigens. We used this experimental model to evaluate the natural killer (NK) activity during the initial phase of the disease. Outbred hamsters infected by intravenous route with 5.106 amastigotes of L. donovani 1S showed a concurrent increase in the spleen weight and in the spleen cell number. Using the single cell assay we detected a significant increase in the percentage of NK effector cells on the 4th day of infection. Imprints from spleen and liver showed at days 14 and 28 a significant increase in the parasite burden. These results show that the increased NK activity in the beginning of the infection was not able to restrain the progression of the disease in this experimental model.

Análise das vantagens de duas técnicas anestésicas - Venosa e inalatória - Para colecistectomia por videolaparoscopia

Background and Objectives - It is essential to reduce health care costs without impairing the quality of care. Propofol is associated to faster recovery and it is known that post-anesthesia care unit (PACU) costs are high. The aim of this study was to evaluate the advantages of two anesthesia regimens - propofol continuous infusion or isoflurane - taking into account the cost of both techniques on PACU stay. Methods - Forty seven patients, physical status ASA I, II and III, undergoing laparoscopic cholecystectomy were divided into 2 groups according to the anesthetic agent: G1, conventional propofol continuous infusion (100-150 μg.kg-1.min-1) and G2, isoflurane. All patients were induced with sufentanil (1 μg.kg-1) and propofol (2 mg.kg-1) and were kept in a re-inhalation circuit (2 L.min-1 of fresh gas flow) with 50% N2O in O2, sufentanil (0.01 μg.kg-1.min-1) and atracurium (0.5 mg.kg-1), or pancuronium (0.1 mg.kg-1) for asthma patients. All patients received atropine and neostigmine at the end of the surgery. Prophylactic ondansetron, dipyrone and tenoxican were administered and, when necessary, tramadol and N-butylscopolamine. Costs of anesthetic drugs (COST), total PACU stay (t-PACU), and PACU stay after extubation (t-EXT) were computed for both groups. Results - Costs were significantly lower in the isoflurane group but t-PACU was 26 minutes longer and t-EXT G1

Eficácia e segurança do uso inalatório da adrenalina-L na laringite pós-intubação utilizada em associação com a dexametasona

Objective: to assess the efficacy and safety of the use of nebulized L-epinephrine associated with dexamethasone in post-intubation laryngitis. Method: we carried out a prospective, randomized, double-blind, placebo controlled study with two cohorts of patients with postintubation laryngitis graded 3 to 6 by Downes and Raphaely score and during two years. Our population was divided into two groups: A and B; both groups received intravenous dexamethasone and nebulized saline with (group B) and without (group A) L-epinephrine. The efficacy was assessed by Downes and Raphaely's score. The side effects of epinephrine were evaluated according to occurrence of arrhythmia, to increased blood pressure, and to average heart rate of group B in comparison to group A. Results: twenty-two patients were included in group A (average score = 4.8) and 19 in group B (average score = 5.2). During treatment, 3 patients in group A presented a score of 8 and were reintubated. This group also showed higher clinical scores than group B during the first two hours of the protocol; these results were not statistically significant. No side effects were observed due to epinephrine. The gasometric parameters were adequate in both groups, but better in the control group. Conclusions: we did not observe increased efficacy for the treatment of post-intubation laryngitis when nebulized L-epinephrine was used simultaneously with intravenous dexamethasone. Some indicators, however, did present a favorable trend when combined therapy was used and should be submitted to further evaluation.

Hepatic bleeding induced by streptokinase and heparin in a patient with acute myocardial infarction

Although rare, major bleeding is the most important side effect of thrombolytic therapy in acute myocardial infarction (AMI) (Levine et al., 1995). Spontaneous hepatic bleeding in normal liver after thrombolytic administration has rarely been reported in literature. To our knowledge, there are only three cases of hepatic bleeding related to thrombolytic therapy in AMI. In these, the used drugs were anisolylated plasminogen streptokinase activator complex (APSAC) (Garcia-Jiménez et al., 1997; Fox et al., 1991) and rt-PA (Garcia-Jiménez et al., 1997). We report a case of hepatic bleeding after streptokinase followed by units over 60 minutes). The next day, the patient developed third-degree atrioventricular block and a temporary pacemaker was inserted. Twenty-seven hours after streptokinase infusion, the patient complained of refractory chest pain that was interpreted as post-myocardial infarction angina; clotting screen was normal and intravenous heparin was started (80 U/kg followed by 18 U/kg/hour). After four hours of heparin administration, the patient presented abdominal pain and distension, and his blood pressure and hematocrit level dropped. Abdominal ultrasonography revealed free fluid in the peritoneal cavity (about 3,000 mL). A laparotomy disclosed blood in the abdominal cavity with bleeding from the right lateral hepatic segment, which was removed. The remaining abdominal viscera were normal and there was no other evidence of hemorrhage. The partial liver resection presented subcapsular hemorrhage with small parenchymal hemorrhage. Histopathological examination also revealed focal areas of ischemic centrilobular necrosis. The patient died of multiple organ system failure 21 days after admission. Copyright © 2002 By PJD Publications Limited.

Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury

Background. Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury. Method. A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n=7) or 15 min (group 2; n=7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview®; Institut National des Télécommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated. Results. Injection of contrast material significantly increased the apparent volume of lung tissue by 83 ± 57 ml in group 1 and 102 ± 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 ± 52 ml and 31 ± 18 ml. Conclusion. Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury, it seems prudent to avoid this procedure in critically ill patients undergoing a thoracic CT scan and to reserve its use for specific indications.

Papel das proteínas Yops de Yersinia pseudotuberculosis na ativação dos linfócitos B

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Progression of liver fibrosis in blood donors infected with hepatitis C virus

Background/Aims. Chronic hepatitis by HCV is progressive towards cirrhosis, with variable rate. We evaluated the rate of fibrosis progression (RFP), risk factors associated with advanced fibrosis (F3 and F4), and estimated the evolution time to cirrhosis. Methods. We transversely selected 142 blood donors infected only with HCV, with a known route of infection, submitted to liver biopsy at admission. RFP= ratio between stage of fibrosis (METAVIR)/estimated duration of infection in years. Non-parametric tests and logistic regression analysis, with significance level of 5% were used. Results. Median RFP was 0.086 U/year (0.05 - 0.142). Ten patients had F4 and 25 had F3. Median RFP values were significantly different (p=0.001) from one age group at contamination to the others and ALT and AST levels. There were no differences in the expected evolution to cirrhosis between intermediate fibrosers (F2) and the rapid fibrosers (F3 and F4). The independent variables associated with advanced fibrosis were ALT (OR 7.2) and GGT (OR 6.4) and age at inclusion (OR 1.12). Conclusion. This study suggests that RFP is extremely variable, it is exponential with age, and mainly influenced by host characteristics, especially age at contamination and possibly ethnical group. These asymptomatic patients had high percentage of fibrosis F2, F3 and F4.

Sildenafil for pulmonary hypertension treatment after cardiac surgery

Objective: To report on the use of sildenafil for pulmonary hypertension treatment of a newborn patient after cardiac surgery. Description: A female, full term newborn infant with diagnosis of double outlet right ventricle, pulmonary hypoplasia and subaortic ventricular septal defect, was submitted to Blalock surgery in the first week of life. In postoperative the newborn had pulmonary hypertension and persistent hypoxia, without response to nitric oxide, but with improved oxygenation after continuous intravenous infusion of prostaglandin E1. After several failed attempts to discontinue prostaglandin E1, oral sildenafil was used. There was a decrease in pulmonary vascular resistance with consequent oxygenation improvement and 48 hours later it was possible to discontinue prostaglandin E1 infusion. Comments: Sildenafil can be an alternative therapy for pulmonary hypertension, especially when there is no response to conventional therapy. Copyright © 2005 by Sociedade Brasileira de Pediatria.

Lack of inhibitory effect of zinc on prolactin secretion induced by cimetidine

The dopaminergic, serotoninergic and GABA-ergic systems are closely involved in PRL secretion, as well as thyrotropin-releasing hormone. There is some evidence that zinc interacts with some of these neuroamines and neuropeptides. The histamine H2-receptor cimetidine stimulates PRL secretion rapidly following an intravenous injection in man. In this sense, we investigated probable inhibitory effect of zinc on prolactin secretion following cimetidine injection (300 mg). Therefore, we studied five healthy adult men, before and after oral zinc administration (25 mg elemental zinc) during three consecutive months. The results did not demonstrate any inhibitory effect of zinc on prolactin secretion. So, we originally concluded that zinc did not interact with dopamine, serotonine, gamma-aminobutyric acid and the thyrotropin-releasing hormone in humans. In addition, the intravenous administration of cimetidine did not change the serum zinc profile. © 2005 Dustri-Vertag Dr. K. Feistle.

Low ethanol consumption induces enhancement of insulin sensitivity in liver of normal rats

Moderate amounts of alcohol intake have been reported to have a protective effect on the cardiovascular system and this may involve enhanced insulin sensitivity. We established an animal model of increased insulin sensitivity by low ethanol consumption and here we investigated metabolic parameters and molecular mechanisms potentially involved in this phenomenon. For that, Wistar rats have received drinking water either without (control) or with 3% ethanol for four weeks. The effect of ethanol intake on insulin sensitivity was analyzed by insulin resistance index (HOMA-IR), intravenous insulin tolerance test (IVITT) and lipid profile. The role of liver was investigated by the analysis of insulin signaling pathway, GLUT2 gene expression and tissue glycogen content. Rats consuming 3% ethanol showed lower values of HOMA-IR and plasma free fatty acids (FFA) levels and higher hepatic glycogen content and glucose disappearance constant during the IVITT. Neither the phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), nor its association with phosphatidylinositol-3-kinase (PI3-kinase), was affected by ethanol. However, ethanol consumption enhanced liver IRS-2 and protein kinase B (Akt) phosphorylation (3 times, P < 0.05), which can be involved in the 2-fold increased (P < 0.05) hepatic glycogen content. The GLUT2 protein content was unchanged. Our findings point out that liver plays a role in enhanced insulin sensitivity induced by low ethanol consumption. © 2005 Elsevier Inc. All rights reserved.

Immune Response to the Rhodococcus equi infection in high and low antibody-producing mice (selection IV-A)

Rhodococcus equi is a Gram-positive, facultative intracellular bacterium which infects macrophages and causes rhodococcal pneumonia and enteritis in foals. Recently, this agent has been recognized as an opportunistic pathogen for immunocompromised humans. Several murine experimental models have been used to study R. equi infection. High (H IV-A) and Low (L IV-A) antibody (Ab)-producers mice were obtained by bi-directional genetic selections for their ability to produce antibodies against sheep and human erythrocytes (Selection IV-A). These lines maintain their phenotypes of high and low responders also for other antigens than those of selection (multispeciflc effect). A higher macrophage activity in L IV-A mice has been described for several intracellular infectious agents, which could be responsible for their intense macrophage antigens (Ag)-handling and low Ab production. Due to these differences, L IV-A mice were found to exhibit a better performance to trigger an effective immune response towards intracellular pathogens. The objective of this work was to characterize the immune response of Selection IV-A against R. equi. H IV-A and L IV-A mice were infected with 2.0 × 10 6 CFU of ATCC 33701 +R. equi by intravenous route. With regards to bacterial clearance and survival assays, L IV-A mice were more resistant than H IV-A mice to virulent R. equi. L IV-A mice presented a higher hydrogen peroxide (H 2O 2) and nitric oxide (NO) endogenous production by splenic macrophages than H IV-A mice. L IV-A expressed the most intense cellular response, available by the Delayed-Type Hypersensitivity (DTH) reaction, which activated macrophages and produced more H 2O 2 and NO. The three times higher specific antibodies titres in H IV-A indicated that Selection IV-A maintained the multispecific effect and the polygenic control of humoral and cellular responses also to R. equi.