Effect of nicorandil upon different guinea-pig and rat isolated organ preparations in vitro

A study of the effect of nicorandil (N-2-(hydroxyethyl)nicotinamide nitrate, CAS 65141-46-0), a potassium channel and guanylatecyclase activator, upon preparations of rat was deferens and uterus, and guinea pig ileum was performed. Nicorandil does not modify rat isolated was deferens responses to noradrenaline (norepinephrine) and potassium. The drug exerts a non-competitive antagonist effect upon rat isolated uterus response to serotonin, histamine, oxytocin, and, at high concentrations, inhibits guinea-pig isolated ileum responses to acetylcholine, histamine, 4-aminopyridine and potassium.     

Sister chromatid exchanges produced by imipramine and desipramine in mouse bone marrow cells treated in vivo

Imipramine and desipramine are two widely used tricyclic antidepressants which have shown conflicting results in regard to their in vitro genotoxic evaluation. The aim of this investigation was to determine the capacity of these compounds to induce in vivo sister-chromatid exchanges (SCEs) in mouse bone marrow cells. For each compound, the animals were organized in five groups constituted by five individuals. They were intraperitoneally (ip) administered with the test substances as follows: a negative control group treated with 0.4 ml of distilled water, a positive control group administered with cyclophosphamide (70 mg/kg), three groups treated with imipramine (7, 20 and 60 mg/kg), and three other groups treated with desipramine (2, 20 and 60 mg/kg). The general procedure included the subcutaneous implantation to each mouse of a 5-bromodesoxyuridine tablet (45 mg), and 1 h later, the administration of the chemicals involved. Twenty-one hours after the tablet implantation, the mice received colchicine, and 3 h later their femoral bone marrow was obtained in KCL, fixed, and stained with the Hoechst-Giemsa method. The results showed that both compounds were SCE inducers, starting from the second tested dose. The response of these compounds was dose-dependent, and showed that the highest tested dose increased about four times the SCE control level. The cellular proliferation kinetics was not affected by the chemicals, and the mitotic indexes were slightly diminished with the highest dose. These results indicate an in vivo genotoxic potential for both chemicals, and suggest that it is pertinent to follow their evaluation in other models.     

Left paramesocolic hernia with retroperitoneal incarceration of jejunum

We present a case left paramesocolic hernia and review the literature. The patients was a 14 years old male and had suffered periods of relapses into abdominal pain from the age of three. When for years old he was operated on using the Nisses technique. Also a laparoscopy had already been performed on this same patient when he was 13 years old, without discovering any pathological conditions. In a new upper gastrointestinal serie, realized one year later, a retroperitoneal incarceration and a paraduodenal loop of jejunum was observed, which obstructed, partially the second part of the duodenum. We have not found the anatomical characteristics of this case in any previous report. In the ample literature pressured, it was confirmed that almost all the clinical cases, previously published had suffered a relapse abdominal pain crisis, diagnosed in advanced states and in/or emergency situations. This produces a mortality rate higher than 20% and or irreparable digestive damage. In cases involving paraduodenal hernias, there exists a low rate of diagnostic suspicion. These delays and diagnostic errors cause irreparable damage. In those patients who suffer relapses into abdominal pain syndrome, one should always include the differential diagnosis of PMH, applying a complete gastrointestinal serie or a CT-Scan with contrast.     

Regulation by nitric oxide of endotoxin-induced tissue factor and plasminogen activator inhibitor-1 in endothelial cells

The increase in nitric oxide (NO) production in lipopolysaccharide (LPS)-induced sepsis is thought to contribute to the development of shock. However, NO could also play an antithrombotic role. Little is known about the modulating effect of NO on the endothelial overexpression and production of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) occurring in endotoxemia. We analyzed the effect of N(G)-nitro-L-arginine-methyl-ester (L-NAME), an inhibitor of NO synthases, and S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a NO donor, on the expression and synthesis of TF and PAI-1 by LPS-challenged human umbilical vein endothelial cells (HUVEC): L-NAME enhanced the increase in TF mRNA and antigen levels (P <0.05) observed in LPS-treated HUVEC; SNAP down-regulated the LPS-induced TF increment (p <0.05). However, no effects of NO on regulation of the LPS-dependent increase in PAI-1 could be seen. Thus, NO could play an antithrombotic role in sepsis by down-regulating the endothelial overexpression and production of TF.     

Sustained ventricular tachycardia as a marker of inadequate myocardial perfusion during the acute phase of myocardial infarction

BACKGROUND: Sustained ventricular tachycardia (VT) complicating the acute phase of myocardial infarction (AMI) is a quite rare event but with short-term unfavorable prognosis. The clinical characteristics as well as the therapeutic implications have not yet been well defined. HYPOTHESIS: This paper attempts to prove that VT may be considered a marker of inadequate myocardial perfusion after thrombolysis. METHODS: To assess the clinic-electroangiographic characteristics and prognosis of patients with VT occurring within the first 4 days of an AMI, a case-control study was carried out in 23 patients from a total of 1,100 patients (1.9%) hospitalized with AMI between March 1993 and July 1997. These patients were compared with a control group of 131 patients hospitalized consecutively. A statistical analysis was made using the chi-square test, t-test, and logistic regression. RESULTS: There were no differences among groups with regard to age, gender, and area of necrosis. Average time for the onset of VT was 26 h (range 0-92 h). Sixteen patients underwent coronary angiography: 4 patients had left main coronary artery disease, 2 had single-vessel disease, 8 had lesions in two vessels, and 2 had triple-vessel disease. Univariate analysis showed that patients with VT had a higher incidence of creatine phosphokinase (CPK)-MB peak > 300 UI/l (61 vs. 30%; p<0.001), more frequent occurrence of previous AMI (48 vs. 17%; p<0.001), and acute intraventricular conduction disorders (26 vs. 4%; p<0.001). Furthermore, these patients suffered ischemia previous to VT more frequently (65 vs. 11%; p<0.0001), and had a greater mortality rate than that in the control group (35 vs. 4%; p<0.0001). In the multivariant analysis, the variables related to the occurrence of VT were CPK-MB peak > 300 IU/l (OR 5.9; 95% CI 1.6-21), acute intraventricular conduction disorders (OR 9.02; 95% CI 1.7-48), and ischemia immediately prior to VT (odds ratio [OR] 19.64; 95% confidence interval [CI] 5.3-73). CONCLUSIONS: Ventricular tachycardia may be considered a marker of inadequate myocardial perfusion after thrombolysis; therefore, a more aggressive revascularization treatment in these patients would be advisable. The profile of patients with AMI, hospitalized in the coronary care unit, who will likely suffer from VT is previous AMI, CPK-MB peak > 300, acute intraventricular conduction disorders, Killip > I, and ischemia previous to VT.     

Whipple's disease with isolated central nervous system symptomatology diagnosed by molecular identification of Tropheryma whippelii in peripheral blood

We report a new case of Whipple's disease (WD) confined to the central nervous system. The patient presented with ataxia, ophthalmoplegia, hypersomnia, hemiparesis and generalized myorhythmia. The diagnosis was confirmed by identification of specific sequences of the causal agent of WD, the actinobacteria Tropheryma whippelii (TW), by PCR of DNA extracted from peripheral blood. An epidemiological survey of TW in patients with dementia suggests that WD is an uncommon cause of dementia in our population. Molecular methods may allow rapid identification of TW in peripheral fluids, and non-invasive diagnosis of this disorder.