Alternative method for oral administration of insoluble toxins to rats. A prenatal study of L-mimosine.

L-mimosine is a compound found in Leucaena leucocephala, that is used as animal feed due to its high protein content, but it can also cause intoxication. Due to its low solubility in organic and aqueous solvents, its administration in laboratory animals is difficult, especially in delicate periods such as pregnancy. Thus, to circumvent such problems, this study proposes a stress-free form of oral administration with gelatin tablets with flavoring (meat broth) for 14 consecutive days of the gestational period (GD06 to GD20). For that, 17 pregnant Wistar rats divided into 3 groups were used: control (CO; n = 5) not treated; gelatin (GEL; n = 6), which received a gelatin tablet with flavoring; and gelatin with flavoring added 140 mg/kg of L-mimosine (GM; n = 6). All animals received feed and water ad libitum. The parameters analyzed were body weight gain, water and feed consumption, serum biochemistry, blood count and reproductive indices. Among these, only the real and total weight gains of dams showed statistically significant differences, with a decrease in the group GM. Thus, we could observe that flavored gelatin was an efficient and effective administration method to insoluble compounds and long-term administration to pregnant rats, with quick adaptation and without refusal by the animals. In addition, we could observe a direct effect of L-mimosine on the animals' weight gain; however, the dose administered was not sufficient to confer maternal and fetal toxicity.

Remote ischemic preconditioning in myocardial protection in hemodialysis patients.

BACKGROUND: Remote ischemic preconditioning (RIPC) is a procedure that generates a brief period of ischemia followed by reperfusion. The role of RIPC in protecting myocardial ischemia during hemodialysis is not yet established. The aim of the study was to evaluate RIPC myocardial protection as evaluated by ultrasensitive I troponin in hemodialysis outpatients. PATIENTS AND METHODS: A double-blind randomized trial with two groups: intervention submitted to RIPC and control group without RIPC. Intervention group received RIPC in three consecutive hemodialysis sessions. Blood samples were taken before and after each session. Blood urea nitrogen for calculation of single-pool Kt/v and ultrasensitive I troponin were measured to evaluate dialysis adequacy and myocardial injury. RESULTS: A total of 47 patients were randomized. About 60.8% were men and 54% were diabetic. The mean single-pool Kt/v was 1.51 in the intervention group and 1.49 in control. The ultrasensitive troponin I measured no significant change from the time of collection: before or after dialysis. CONCLUSION: The RIPC applied in three consecutive sessions did not demonstrate superiority to control, therefore another study tested RIPC in 12 consecutive sessions with a positive result in myocardial protection. In our study, more than half of the patients were diabetic. Diabetic patients have a trend to show a lower response to RIPC because of the greater presence of collateral coronary circulation. In summary, in this model there was no interference of RIPC in ultrasensitive troponin I values, but troponin had a high negative predictive value for myocardial infarction in all tested models.

Inability of Turbidimetry Method in Detecting Glycated Hemoglobin to Select Diabetes Mellitus Patients According to Their Concentrations of Blood Glucose Levels.

BACKGROUND: Diabetes mellitus is a chronicle illness in which there is a high blood glucose level defined as hyperglycemia, resulted by a deficiency in insulin secretion and/or in its action. Nowadays, it is being seen as a public health problem and is reaching increasing proportions with regard to the appearance of new cases. For diagnosis, sensible and accurate methods should be used to avoid complications of the sickness. The measure of glycated hemoglobin may not be used for diagnosis, but is the reference method to evaluate the grade of glycemic control in the long term, reflecting the blood glucose level in the latest 2-3 months. The aim of this study was to evaluate the grade of concordance between turbidimetry and liquid chromatography methods in the glycated hemoglobin determination and to estimate the sensibility and specificity values of turbidimetry. METHODS: This study included 133 blood samples obtained from patients and healthy donors, ageing between 18 and 80 years with glycemic values between 58 and 473 mg/dl. RESULTS AND CONCLUSION: Turbidimetry is a useful method for determining glycemic levels above 100 and over 200 mg/dl, but does not have the ability to select samples with intermediary blood glucose concentrations.

Endothelial, renal and hepatic variables in Wistar rats treated with Vancomycin.

Vancomycin (VCM) is indicated in combat against Gram-positive infections, but it is not considered a first-choice drug because of its adverse effects. It is believed that oxidative stress is the primary mechanism of endothelial injury and the consequent VCM toxicity, which varies from phlebitis to nephrotoxicity. Moreover, dose recommendations, dilution, rates and types of infusion are still controversial. The aim of this study was to determine the effect of different VCM dilutions in endothelial, liver and kidney injuries by biochemical parameters and histopathological analysis. Wistar rats were randomly divided into six groups and subjected to femoral vein cannulation for drug administration. Control groups received 0.9 ml of saline and the others received VCM (10mg/Kg/day) at dilutions of 5.0 and 10.0 mg/mL for 3 and 7 days. Homocysteine, hs-CRP, AST, ALT, GGT, urea, creatinine, lycopene, alpha-tocopherol, beta-carotene and retinol were analyzed. Kidney, liver and cannulated femoral vein fragments were collected.This study showed alterations in ALT which featured hepatotoxicity. However, drug dilutions were not able to show changes in other biochemical parameters. In contrast, kidney and endothelium pathological changes were observed. More studies are needed to characterize VCM induced kidney and endothelium toxicity and biochemical markers able to show such morphological modifications.

Standardization of a method to study angiogenesis in a mouse model.

In the adult organism, angiogenesis is restricted to a few physiological conditions. On the other hand, uncontrolled angiogenesis have often been associated to angiogenesis-dependent pathologies. A variety of animal models have been described to provide more quantitative analysis of in vivo angiogenesis and to characterize pro- and antiangiogenic molecules. However, it is still necessary to establish a quantitative, reproducible and specific method for studies of angiogenesis factors and inhibitors. This work aimed to standardize a method for the study of angiogenesis and to investigate the effects of thalidomide on angiogenesis. Sponges of 0.5 x 0.5 x 0.5 cm were implanted in the back of mice groups, control and experimental (thalidomide 200 mg/K/day by gavage). After seven days, the sponges were removed. The dosage of hemoglobin in sponge and in circulation was performed and the ratio between the values was tested using nonparametric Mann-Whitney test. Results have shown that sponge-induced angiogenesis quantitated by ratio between hemoglobin content in serum and in sponge is a helpful model for in vivo studies on angiogenesis. Moreover, it was observed that sponge-induced angiogenesis can be suppressed by thalidomide, corroborating to the validity of the standardized method.

Incidence of Leptospirosis infection in the East Zone of Sao Paulo City, Brazil.

BACKGROUND: Leptospirosis is a zoonosis which is spread through contamined running water. This contaminations is seriously affected by the flooding which occurs in the area surrounding the Aricanduva river. The transmission of the disease results mainly from the contact of water with soil contaminated by the urine of infected animals. We aimed to conduct an epidemiological survey on Leptospirosis cases in Sao Paulo East Zone area. METHOD: The analysis conducted in this study was based on data collected from the health authorities of that region close the Aricanduva river between 2007 and 2008 years, which give the rates of confirmed cases, mortality and death from human Leptospirosis. Other information concerned with the relationships among rainfall index, points of flooding and incidence of Leptospirosis. RESULTS: We observed a direct and important water contamination. Records of flooding points and dates of the reported cases in the region showed a direct relationship from which the period of higher rainfall also recorded an increase in cases. The annual record of the city and the region and rainfall regions also presented correlation. CONCLUSION: The association between the indices of flooding and Leptospirosis cases indicates that preventive measures are necessary to avoid exposing the community.

Antioxidant effect of simvastatin is not enhanced by its association with alpha-tocopherol in hypercholesterolemic patients.

Among the pleiotropic effects of statins, their antioxidant action may be involved in their protective effects. Thus, we investigated the antioxidant effect of simvastatin, associated or not with alpha-tocopherol, on levels of electronegative low-density lipoprotein (LDL-), nitrotyrosine, thiols (homocysteine, glutathione, cysteine, methionine), and lipid-soluble antioxidants in blood plasma of hypercholesterolemic subjects. In this study, 25 hypercholesterolemic subjects were treated for 2 months with simvastatin (20 mg/day) and with simvastatin (20 mg/day) + alpha-tocopherol (400 IU/day). Concentrations of thiols were determined by high-performance capillary electrophoresis-laser-induced fluorescene. Lipid-soluble antioxidants were determined by HPLC, and LDL-, and nitrotyrosine by ELISA. Simvastatin, independent of its association with alpha-tocopherol, reduced plasma concentrations of LDL-, nitrotyrosine, total cholesterol, and LDL cholesterol and the LDL cholesterol/HDL cholesterol ratio. Neither simvastatin nor simvastatin plus alpha-tocopherol altered plasma levels of the thiols analyzed. alpha-Tocopherol did not change the antioxidant effect of simvastatin on the levels of LDL- and nitrotyrosine in hypercholesterolemic subjects. The reduction of LDL- and nitrotyrosine by simvastatin seems to be related to the pleiotropic effects of this statin, and it may have an important protective effect against endothelial dysfunction and atherosclerosis.

Antioxidant effect of simvastatin is not enhanced by its association with a-Tocopherol in hypercholesterolemic patient

Among the pleiotropic effects of statins, their antioxidant action may be involved in their protective effects.Thus, we investigated the antioxidant effect of simvastatin, associated or not with a-tocopherol, on levels ofelectronegative low-density lipoprotein (LDL ), nitrotyrosine, thiols (homocysteine, glutathione, cysteine, methionine),and lipid-soluble antioxidants in blood plasma of hypercholesterolemic subjects. In this study, 25 hypercholesterolemicsubjects were treated for 2 months with simvastatin (20 mg/day) and with simvastatin (20 mg/day) + a-tocopherol (400IU/day). Concentrations of thiols were determined by high-performance capillary electrophoresis–laser-inducedfluorescene. Lipid-soluble antioxidants were determined by HPLC, and LDL , and nitrotyrosine by ELISA. Simvastatin,independent of its association with a-tocopherol, reduced plasma concentrations of LDL , nitrotyrosine, totalcholesterol, and LDL cholesterol and the LDL cholesterol/HDL cholesterol ratio. Neither simvastatin nor simvastatinplus a-tocopherol altered plasma levels of the thiols analyzed. a-Tocopherol did not change the antioxidant effect ofsimvastatin on the levels of LDL and nitrotyrosine in hypercholesterolemic subjects. The reduction of LDL andnitrotyrosine by simvastatin seems to be related to the pleiotropic effects of this statin, and it may have an importantprotective effect against endothelial dysfunction and atherosclerosis.

Effects of simvastatin and L-arginine on vasodilation, nitric oxide metabolites and endogenous NOS inhibitors in hypercholesterolemic subjects.

Hypercholesterolemia is linked to endothelial dysfunction and enhancement of the endogenous inhibitor of NO synthase. The statins have lipid-lowering and pleiotropic properties, which could exert protective effects on the endothelium in hypercholesterolemia. The association of L-arginine with simvastatin could promote a further improvement on endothelial function in this condition. Thus, we investigated whether simvastatin, with or without supplementation with L-arginine, could improve endothelium-dependent vasodilation. In this study, 25 hypercholesterolemic subjects were treated according to the following protocol: washout period of 1 month; simvastatin (20 mg/day) for 2 months; simvastatin (20 mg/day) + L-arginine (7 g/day) for 2 months. From these patients, 10 were chosen at random for evaluation of vascular function by high resolution ultrasonography of the brachial artery. In subjects treated with simvastatin plus L-arginine, an increase of L-arginine levels (68%) and L-arginine/asymmetric dimethylarginine (ADMA) ratio (67%) were observed. Simvastatin reduced the plasma concentrations of NO metabolites nitrite + nitrate (NOx: 34%), S-nitrosothiols (RSNO: 42%), total cholesterol (25%), low density lipoprotein (LDL)-cholesterol (36%) and the LDL-cholesterol/high density lipoprotein (HDL-cholesterol ratio (34%). Simvastatin, associated or not to L-arginine, did not affect ADMA levels and endothelium-dependent vasodilation. Our data showed that simvastatin reduced the plasma concentrations of NOx and RSNO without affecting either the levels of ADMA or endothelium-dependent vasodilation in hypercholesterolemia.

Effects of Simvastatin and L-arginine on vasodilation, nitric oxide metabolics and endogenous NOS Inhibitors in hypercholesterolemic subjects

The statins have lipid-lowering and pleiotropic properties, which could exert protective effects on the endothelium in hypercholesterolemia. The association of L-arginine with simvastatin could promote a further improvement on endothelial function in this condition. Thus, we investigated whether simvastatin, with or without supplementation with L-arginine, could improve endothelium-dependent vasodilation. In this study, 25 hypercholesterolemic subjects were treated according to the following protocol: washout period of 1 month; simvastatin (20 mg/day) for 2 months; simvastatin (20 mg/day) þ L-arginine (7 g/day) for 2 months. From these patients, 10 were chosen at random for evaluation of vascular function by high resolution ultrassonography of the brachial artery. In subjects treated with simvastatin plus L-arginine, an increase of L-arginine levels (68%) and L-arginine/asymmetric dimethylarginine (ADMA) ratio (67%) were observed. Simvastatin reduced the plasma concentrations of NO metabolites nitrite þ nitrate (NOx: 34%), S-nitrosothiols (RSNO: 42%), total cholesterol (25%),low density lipoprotein (LDL)-cholesterol (36%) and the LDL-cholesterol/high density lipoprotein (HDL)-cholesterol ratio (34%). Simvastatin, associated or not to L-arginine, did not affect ADMA levels and endotheliumdependent vasodilation. Our data showed that simvastatin reduced the plasma concentrations of NOx and RSNO without affecting either the levels of ADMA or endothelium- dependent vasodilation in hypercholesterolemia...

Alcaptonúria: relato de dois casos e revisão bibliográfica / Alcaptonuria: A propos of two cases and bibliographic review

A alcaptonúria é uma doença rara, na qual ocorre a formaçäo de um pigmento que se acumula na cartilagem, pele e tecidos conectivos (ocronose), resultando em artrite, lesöes cardiovasculares, hiperpigmentaçäo da pele e outras patologias. Os autores descrevem dois casos de alcaptonúria, detectados em dois irmäos, sendo um do sexo masculino, com idade de 12 anos, e outro do sexo feminino, com dois meses de idade, que foram diagnosticados através da anamnese e dosagem de AH urinário por cromatografia.