Cláudio Galeano Zettler

DNA damage in brain cells of mice treated with an oxidized form of apomorphine.

We investigated whether systemic injection of apomorphine and its oxidation derivative 8-oxo-apomorphine-semiquinone (8-OASQ) could induce DNA damage in mice brain, using the single-cell gel assay. 8-OASQ induced DNA damage in the brains at 1 and 3 h, but not at 24 h after treatment whereas apomorphine induced a slight increase in brain DNA damage frequency at 3 h after treatment, suggesting that both drugs display genotoxic activity in brain tissue.

Protective effect of allopurinol in the renal ischemia–reperfusion in uninephrectomized rats

The effect of allopurinol (an inhibitor of xanthine oxidase) on oxidative stress, renal dysfunction, and histologic alterations was evaluated during the renal ischemia--reperfusion in uninephrectomized rats. Renal malondialdehyde and serum creatinine levels significantly increased after renal ischemia--reperfusion. However, the pretreatment with allopurinol demonstrated a protector effect in these parameters. Renal ischemia--reperfusion provoked a significant renal damage in the operated group. Tubular atrophy and interstitial fibrosis were attenuated by allopurinol when given prior to the surgery. In our study, allopurinol had a strong tendency to exert a beneficial effect during renal ischemia--reperfusion in uninephrectomized rats.

The role of nitric oxide pathway in the renal ischemia-reperfusion injury in rats.

INTRODUCTION Nitric oxide (NO), synthesized from L-arginine by the enzyme nitric oxide synthase (NOS), seems to play an ambiguous role during tissue ischemia-reperfusion injury. Our objective was to evaluate the effects of L-arginine, a NO donor, and N(G)-nitro-L-arginine-methylester (L-NAME), a NOS inhibitor, on oxidative stress, renal dysfunction, histologic alterations and surgical mortality rate induced by renal ischemia-reperfusion (RIR) in uninephrectomized rats. MATERIALS AND METHODS One-hundred and ninety-seven Wistar rats were randomized into five experimental groups. Group 1: sham operation; group 2: right uninephrectomy (UNI); group 3: UNI + RIR in the contralateral kidney; group 4: UNI + L-NAME (20 mg/kg; intraperitoneally) + RIR; and group 5: UNI + L-arginine + RIR. The effect of the drugs was evaluated by lipid peroxidation measured by the renal malondialdehyde (MD) content and chemiluminescence (CL) levels, serum creatinine (Cr) levels, urinary volume, tubular necrosis and athrophy, inflammatory infiltrate, interstitial fibrosis as histologic evaluation and surgical mortality rate after the procedures. A P value less than 0.05 was considered significant. RESULTS Right uninephrectomy did not alter the renal parameters. RIR increased Cr levels (at 24 and 96 h of reperfusion), index of lipid peroxidation (both MD and QL levels), and worsened the histologic aspects. Pretreatment with L-arginine reduced the kidney levels of QL when compared with the non-treated group (5574 +/- 909 vs. 13 660 +/- 1104 cps/mg of protein; P < 0.05) but increased the MD levels (0.97 +/- 0.24 vs. 0.79 +/- 0.06 nmol/mg of protein; P < 0.05). Moreover, L-arginine attenuated the increment of Cr levels, inflammatory infiltrate and tubular athrophy in rats subjected to RIR (P < 0.05). On the other hand, pretreatment with L-NAME increased both CL (17 482 +/- 4397 vs. 13 660 +/- 1104 cps/mg of protein; P < 0.05) and MD levels (1.16 +/- 0.11 vs. 0.79 +/- 0.06 nmol/mg of protein; P < 0.05). Furthermore, L-NAME worsened the renal dysfunction (P < 0.05) at 192 h after the RIR, and surgical mortality rates were similar (P > 0.05). CONCLUSION L-arginine has a tendency to exert a beneficial effect on renal damage during RIR in rats. Moreover, L-NAME seems to worsen the renal damage by increasing the kidney-levels of CL and impairment of renal function probably due to reduction of NO production.

Ki-67 and p53 correlation prognostic value in squamous cell carcinomas of the oral cavity and tongue.

UNLABELLED Epidermoid carcinomas represent from 90% to 95% of oral cavity malignant neoplasias, making up 13,470 cases/year. AIMS To correlate p53 and Ki-67 expressions in mouth and tongue carcinomas with lymph node status, gender, histological grade, tumor volume and pathological stage. MATERIALS AND METHODS We carried out a retrospective study of 28 cases of mouth and tongue epidermoid carcinomas. They were submitted to immunohistochemical study in order to check the expression of p53 and Ki-67 antibodies and statistically compare them in terms of lymph node status, gender, histological grade, tumor volume and pathological staging. RESULTS The individually analyzed p53 proved to have statistical significance (p<0.05) when compared to tumor volume (p=0.029). Despite a strong tendency, the p53/tumor volume relation was not significant. When p53 + Ki67 were analyzed, tumor volume had p < 0.05 (p = 0.029). DISCUSSION Literature shows that the expression of p53 and Ki-67 is related to the presence of metastasis to lymph nodes and a worse prognosis. CONCLUSION In oral cavity and tongue epidermoid carcinomas, p53 and Ki-67 are related to larger tumors, metastasis to lymph nodes and very likely to a worse prognosis.

Uso de quercetina a longo prazo em ratos cirróticos

PURPOSE: The long term use of quercetin flavonoid was evaluated in cirrhotic rats by common biliary duct bondage (LDB). METHODS: 32 male Wistar rats were submitted to LDB or simulation, and distributed in 4 groups: 1) control, 2) cirrhotic, 3) cirrhotic treated with quercetin the second day after the surgical procedure; and 4) cirrhotic treated with quercetin after the fourteenth day of the surgical procedure. The hepatic function was analyzed through biochemical tests (TB and DB) and enzymatic activity (ALT, AST, AP and GGT). In the anatomopatological analysis, Hematoxilin & Eosin (HE Group 2 = 46 days; Group 3 = 71 days; and the Group 4 = 90 days. In the animals with bondage of common biliary duct, there was an increase of the hepatic and anzymatic function tests, which was reduced with the treatment with quercetin. Cirrhosis, portal and centrolobular vascular congestion, were identified in the histopatological analysis with H&E and Picrosirius. CONCLUSION: The use of quercetin decreased significantly the biochemical alterations caused by cirrhosis, increasing the time of survival of the animals with secondary biliary cirrhosis due to LDB.

Nonalcoholic Steatohepatitis in Nondiabetic Obese Patients

BACKGROUND Nonalcoholic steatohepatitis (NASH) is a major disorder in patients with persistent changes in aminotransferase activity who test negative for viral markers and autoantibodies. Although NASH has been correlated with obesity, no study has been carried out exclusively with nondiabetic obese patients. OBJECTIVES To evaluate the occurrence of NASH in obese patients without diabetes mellitus and to assess the severity of histological involvement of the liver. PATIENTS AND METHODS Serum aminotransferase levels were evaluated in 912 obese patients seen at an outpatient clinic in Porto Alegre, Brazil, from 1997 to 1999. Sixty-eight patients were found to have altered aminotransferase levels in more than one test. Thirty-five patients were excluded due to the presence of diabetes mellitus (n=12), the presence of viral markers (n=11), alcohol consumption (n=8) and the use of hepatotoxic drugs (n=4). NASH was diagnosed when histological findings revealed macrovesicular steatosis associated with lobular inflammatory infiltrate and hepatocellular injury. RESULTS Of the 912 obese patients studied, 33 patients with altered aminotransferase levels underwent liver biopsy. Four patients were excluded because they had steatosis only; the remaining 29 patients (3.18%) fulfilled the diagnostic criteria established for NASH. The mean age of the 29 patients was 42.2 +/- 11.9 years; 65.52% of the patients were women. Grading of histological findings revealed mild disease in 58.6% of cases; important proliferation of fibrous tissue was absent in most cases. CONCLUSIONS NASH is a common disease among nondiabetic obese patients with altered aminotransferase levels, and it usually manifests as a mild clinical condition, although more severe lesions may be observed.

The effect of maternal hypercholesterolemia on the placenta and fetal arteries in rabbits

PURPOSE To investigate the degree of placental permeability in dyslipidemic rabbits and the consequent vascular dysfunction in fetuses of female rabbits with high lipoprotein levels. METHODS Fifteen adult females New Zealand White rabbits were divided into two groups. Group 1(n=5) - hypercholesterolemic diet with 0.5% cholesterol, and Group 2 (n=10) - control. On day 30, the levels of plasma lipoproteins and triglycerides were analyzed in the mothers, and the presence of collagen was analyzed in the placenta as well as in fetal coronary and aorta. Statistical analyses used the Students t and the Mann-Whitney tests. RESULTS Lipoprotein levels were significantly different (p=0.02 to p<0.001) in experimental and control groups. In the hypercholesterolemic group, total cholesterol levels were in average 793 mg/dl; triglycerides were in average 257 mg/dl; HDL-C was 48 mg/dl, and LDL-C was in average 692 mg/dl. The amount of collagen per micrometers square (mµ²) in samples from hypercholesterolemic animals was significantly higher than in the control group. CONCLUSIONS The study confirmed placental permeability to lipoproteins, shown by increased amounts of collagen in fetal tissues. This alteration results in increased susceptibility to atherosclerosis in adult life, representing a risk factor for the early development of disease, which may appear even in the prenatal period.

Effects of L-arginine and L-NAME on ischemia-reperfusion in rat liver

PURPOSE To evaluated the effects of L-arginine (a NO donor) and L-NAME (Nw-nitro-L-arginine methyl ester - a NOS inhibitor) on ischemia-reperfusion in rat livers. METHODS One hundred fifty two male Wistar rats were divided into four groups: control (simulated surgery); hepatic IR; pretreatment with L-arginine plus hepatic IR; and L-NAME plus hepatic IR. The hepatocellular damage was evaluated at the first, third and seventh days after the procedures through the alanine-aminotransferase (ALT) and aspartate-aminotransaminase (AST) levels, as well as histopathological features: vascular congestion (VC); steatosis (STE); necrosis (NEC); and inflammatory infiltration (INF). The mortality rate was also evaluated. RESULTS The pretreatment with L-NAME significantly worsened the AST levels after hepatic IR (p<0.05) at first day and L-arginine demonstrated an attenuating effect on ALT levels at seventh day (p<0.05). Furthermore, the administration of L-arginine was able to reduce the VC and STE in the seventh day after hepatic IR (p<0.05). The analysis of the mortality rates did not demonstrate any difference between the groups. Nevertheless, there was not effect of L-arginine and L-NAME on the mortality of the animals. CONCLUSION L-arginine/NO pathway has a role in the hepatic IR because the pretreatment with L-arginine partially had attenuated the hepatocellular damage induced by hepatic IR in rats.

The presence of metastases in regional lymph nodes is associated with tumor size and depth of invasion in sporadic gastric adenocarcinoma

Background Gastric adenocarcinoma is more often found in men over 50 years in the form of an antral lesion. The tumor has heterogeneous histopathologic features and a poor prognosis (median survival of 15% in five years). Aim To estimate the relationship between the presence of nodal metastasis and other prognostic factors in sporadic gastric adenocarcinoma. Method Were evaluated 164 consecutive cases of gastric adenocarcinoma previously undergone gastrectomy (partial or total), without clinical evidence of distant metastasis, and determined the following variables: topography of the lesion, tumor size, Borrmann macroscopic configuration, histological grade, early or advanced lesions, Lauren histological subtype, presence of signet ring cell, degree of invasion, perigastric lymph node status, angiolymphatic/perineural invasion, and staging. Results Were found 21 early lesions (12.8%) and 143 advanced lesions (87.2%), with a predominance of lesions classified as T3 (n=99/60, 4%) and N1 (n=62/37, 8%). The nodal status was associated with depth of invasion (p<0.001) and tumor size (p<0.001). The staging was related to age (p=0.048), histological grade (p=0.003), and presence of signet ring cells (p = 0.007), angiolymphatic invasion (p = 0.001), and perineural invasion (p=0.003). Conclusion In gastric cancer, lymph node involvement, tumor size and depth of invasion are histopathological data associated with the pattern of growth/tumor spread, suggesting that a wide dissection of perigastric lymph nodes is a fundamental step in the surgical treatment of these patients.

Leiomioma hepático em paciente imunocompetente

Diagnosis and treatment of hepatic tumors are a challenge for the surgeon in some situations. There are many histologic types of these neoplasms, and their diagnoses are increasing. Leyomioma of the liver is a rare pathology that is presented in this article in a 44 years old woman without immunosuppression. A review about its clinical aspects, image diagnosis and surgical therapy is discussed, based on the world medical literature.