Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non alcoholic fatty liver disease in rats

AIM： To evaluate the potential of S-nitroso-N-acetylcysteine （SNAC） in inhibition of lipid peroxidation and the effect of oral SNAC administration in the prevention of nonalcoholic fatty liver disease （NAFLD） in an animal model.METHODS： NAFLD was induced in Wistar male rats by choline-deficient diet for 4 wk. SNAC-treated animals （n=6） （1.4 mg/kg/day of SNAC, orally） were compared to 2 control groups： one （n=6） received PBS solution and the other （n=6） received NAC solution （7 mg/kg/d）. Histological variables were semiquantitated with respect to macro and microvacuolar fat changes, its zonal distribution, foci of necrosis, portal and perivenular fibrosis, and inflammatory infiltrate with zonal distribution. LOOHs from samples of liver homogenates were quantified by HPLC. Nitrate levels in plasma of portal vein were assessed by chemiluminescence. Aqueous low-density lipoprotein （LDL） suspensions （200 pg protein/mL） were incubated with CuCl2 （300 μmol/L） in the absence and presence of SNAC （300 μmol/L） for 15 h at 37 ℃ Extent of LDL oxidation was assessed by fluorimetry. Linoleic acid （LA） （18.8 μmol/L） oxidation was induced by soybean lipoxygenase （SLO） （0.056 μmol/L） at 37 ℃ in the presence and absence of N-acetylcysteine （NAC） and SNAC （56 and 560 pmol/L） and monitored at 234 nm. RESULTS： Animals in the control group developed moderate macro and microvesicular fatty changes in periportal area. SNAC-treated animals displayed only discrete histological alterations with absence of fatty changes and did not develop liver steatosis. The absence of NAFLD in the SNAC-treated group was positively correlated with a decrease in the concentration of LOOH in liver homogenate, compared to the control group （0.7±0.2 nmol/mg vs 3.2±0.4 nmol/mg protein, respectively, P〈0.05）, while serum levels of aminotransferases were unaltered. The ability of SNAC in preventing lipid peroxidation was confirmed in in vitro experiments using LA and LDL as model substrates. CONCLUSION： Oral administration of SNAC prevents the onset of NAFLD in Wistar rats fed with cholinedeficient diet. This effect is correlated with the ability of SNAC to block the propagation of lipid peroxidation in vitro and in vitro.

Pre-and postoperative systemic hemodynamic evaluation in patients subjected to esophagogastric devascularization plus splenectomy and distal splenorenal shunt:A comparative study in schistomomal portal hypertension

AIM: To investigate the systemic hemodynamic effects of two surgical procedures largely employed for treatment of schistosomal portal hypertension. METHODS: Thirty-six patients undergoing elective surgical treatment of portal hypertension due to hepatosplenic mansonic schistosomiasis were prospectively evaluated. All patients were subjected to preoperative pulmonary artery catheterization; 17 were submitted to esophagogastric devascularization and splenectomy (EGDS) and 19 to distal splenorenal shunt (DSRS). The systemic hemodynamic assessment was repeated 4 d after the surgical procedure. RESULTS: Preoperative evaluation revealed (mean ± SD) an increased cardiac index (4.78 ± 1.13 L/min per m2),associated with a reduction in systemic vascular resistance index (1457 ± 380.7 dynes.s/cm5.m2). The mean pulmonary artery pressure (18 ± 5.1 mmHg) as well as the right atrial pressure (7.9 ± 2.5 mmHg) were increased,while the pulmonary vascular resistance index (133 ± 62 dynes.s/cm5.m2) was decreased. Four days after EGDS,a significant reduction in cardiac index (3.80 ± 0.4 L/min per m2,P < 0.001) and increase in systemic vascular resistance index (1901.4 ± 330.2 dynes.s/cm5. m2,P < 0.001) toward normal levels were observed. There was also a significant reduction in pulmonary artery pressure (12.65 ± 4.7 mmHg,P < 0.001) and no significant changes in the pulmonary vascular resistance index (141.6 ± 102.9 dynes.s/cm5.m2). Four days after DSRS,a non-significant increase in cardiac index (5.2 ± 0.76 L/min per m2) and systemic vascular resistance index (1389 ± 311 dynes.s/cm5.m2) was observed. There was also a non-significant increase in pulmonary artery pressure (19.84 ± 5.2 mmHg),right cardiac work index (1.38 ± 0.4 kg.m/m2) and right ventricular systolic work index (16.3 ± 6.3 g.m/m2),without significant changes in the pulmonary vascular resistance index (139.7 ± 67.8 dynes.s/cm5.m2). CONCLUSION: The hyperdynamic circulatory state observed in mansonic schistosomiasis was corrected by EGDS,but was maintained in patients who underwent DSRS. Similarly,the elevated mean pulmonary artery pressure was corrected after EGDS and maintained after DSRS. EGDS seems to be the most physiologic surgery for patients with schistosomal portal hypertension.

Surgical treatment of familial adenomatous polyposis: Dilemmas and current recommendations

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome characterized by multiple adenomatous polyps (predisposing to colorectal cancer development) and numerous extracolonic manifestations. The underlying genetic burden generates variable clinical features that may influence operative management. As a precancerous hereditary condition, the rationale of performing a prophylactic surgery is a mainstay of FAP management. The purpose of the present paper is to bring up many controversial aspects regarding surgical treatment for FAP, and to discuss the results and perspectives of the operative choices and approaches. Preferably, the decision-making process should not be limited to the conventional confrontation of pros and cons of ileorectal anastomosis or restorative proctocolectomy. A wide discussion with the patient may evaluate issues such as age, genotype, family history, sphincter function, the presence or risk of desmoid disease, potential complications of each procedure and chances of postoperative surveillance. Therefore, the definition of the best moment and the choice of appropriate procedure constitute an individual decision that must take into consideration patient&#x02019;s preferences and full information about the complex nature of the disease. All these facts reinforce the idea that FAP patients should be managed by experienced surgeons working in specialized centers to achieve the best immediate and long-term results.

Melanoma of the gallbladder misdiagnosed as gallbladder cancer

To the Editor:Metastatic melanoma of the gallbladder is extremely rare,and despite appropriate therapy its prognosis is poor withfew patients surviving more than 2 years. We present acase of gallbladder involvement by malignant melanomain a