Short coupled variant of torsade de pointes: our experience and review of the literature

We present three cases of short-coupled variant of torsade de pointes with review of the literature. These women presented with syncope or presyncope due to torsade de pointes initiated by a short-coupled premature ventricular beat and without evidence of prolonged QT. There were no electrolyte disturbances in all cases, no apparent structural heart disease in two cases and a mild interventricular septum hypertrophy in the other case. One patient took spiramycin and metronidazole and another was taking pheniramin and lincomycin without any evidence of cause to effect relationship. One patient responded to verapamil but died suddendly after 44 months of follow-up. The two others recieved implantable cardioverter-defibrillators and verapamil per os. They still alive 46 and 54 months later. Short-coupled variant of torsade de pointes have a high incidence of sudden death, so it is very important for physicians to identify and treat it promptly. Long-term verapamil treatement is effective but still insufficient and patients should be considered for implantable cardioverter-defibrillator therapy.     

Bacteriologic features of urinary tract infections in children in the Sousse area, Tunisia

Urinary tract infection (UTI) is frequent in childhood. Our purpose is to determine the bacteriologic profile of UTI in children through a retrospective study of 1281 urinary specimens analysed in the Laboratory of Microbiology of F. Hached University hospital of Sousse between 1997 and 2002 (2000 except). The most frequent pathogens recovered were E. coli (71%), K. pneumoniae (10%) P. mirabilis (8%), Staphylococcus (1.6%), P. aeruginosa (1%) and others (2%). E. coli susceptibility to antibiotics was characterised by the high resistance percentage to amoxicillin (60%), to amoxicilline - acid clavulanic (54%) and to cotrimoxazole (40%). The resistance percentage to third generation cephalosporins, to aminoglycosides and to nitrofurane remained very low, respectively of 1.5%, 1% and 1%. High resistance rates among K. pneumoniae strains towards to amoxicillin - acid clavulanic and Cefotaxim, respectively of 63 and 39% were noticed. The resistance percentages to amikacin and cotrimoxazole were respectively of 17 and 65%, but only of 4% to nitrofurane. 70% of P. mirabilis strains were resistant to amoxicillin, 63% of them remained susceptible to amoxicillin - acid clavulanic. No resistance was shown to amikacin against 31% towards cotrimoxazole.     

Serum selenium is associated with plasma homocysteine concentrations in elderly humans

Low selenium levels in humans have been associated with several pathologies; however, an earlier animal investigation found a direct association between Se intake and total plasma homocysteine (tHcy) concentrations. To date, the importance of serum selenium levels in association with tHcy in humans has not been determined. We evaluated the cross-sectional association of blood selenium concentrations with plasma tHcy and other determinants of this cardiovascular disease risk factor. We estimated protein intake and measured the blood status of selenium, tHcy, and several other related factors in serum such as folate, vitamin B-12, and creatinine. Serum selenium was inversely associated with tHcy, explaining 5.8% of tHcy variance with respect to 2.2% accounted for by serum folate. Furthermore, there was a 63% decreased risk of higher tHcy concentrations (>14 micro mol/L) for subjects with serum selenium in the highest tertile (P = 0.013). We also found an inverse association of protein intake with tHcy in men (beta = -0.144; P = 0.036), which disappeared after controlling for serum Se concentrations (beta = -0.055; P = 0.003). In conclusion, selenium should be considered as a potential factor to lower tHcy. In addition, the described association between protein intake and homocysteine levels could be mediated by this trace element.     

Well-characterized garlic-derived materials are not hypolipidemic in APOE*3-Leiden transgenic mice

Garlic is reported to have beneficial effects on risk factors associated with cardiovascular disease, including normalization of plasma lipid levels. However, numerous studies do not support this beneficial effect of garlic on plasma lipids. This contradiction may result from the use of different garlic-derived materials, experimental designs, and/or animal models. The present study investigated the hypolipidemic effect of garlic-derived materials in APOE*3-Leiden mice, a model well suited for drug and dietary intervention studies of hyperlipidemia. APOE*3-Leiden mice were fed a garlic-derived sulfur-rich compound, either allicin (0.29 g.L drinking water(-1)) or diallyldisulfide (0.27 g.kg diet(-1)), or powdered garlic, of either the kwai (42 g.kg diet(-1)) or morado (42 g.kg diet(-1)) variety. The amounts of garlic-derived materials supplied allowed free intake of allicin or allicin equivalents (diallyldisulfide, kwai, or morado) at 44 mg.kg body wt(-1).d(-1). Mice were fed a nonpurified diet for 4 wk, followed by a Western diet for 8 wk, both supplemented with the garlic-derived materials. These diets had no consistent effect on plasma lipids and did not affect lipoprotein profiles, which are markers for whole-body cholesterol synthesis and intestinal sterol absorption. The current data indicate that the postulated effects of garlic on cardiovascular disease are not caused via modulation of plasma lipid levels.     

The impact of health-management training programs in Latin America on job performance

A study was undertaken in Mexico, Colombia, and El Salvador to determine the impact of a management training program on health managers' job performance. A quasi-experimental design was used where in the baseline study an intervention group of 85 district health managers in the three countries was compared with a control group of 71 managers who did not receive the training program. After the implementation of an 18-month training program (which included 5-day training workshops and a series of tasks to be carried out between the workshops), the outcome in terms of improved job performance (i.e. use of predefined management techniques) was measured through twelve management performance indicators. The data collection tools were two questionnaires, participant observation in managers' workplaces, focus group discussions, staff interviews, and document analysis. In Mexico, the control group showed 8.3 times weaker management performance compared to the intervention group; in Colombia the value was 3.6 and in El Salvador 2.4. Factors associated with a successful training outcome were: (a) training techniques, (b) strengthening of enabling factors, and (c) reinforcement mechanisms.     

Inhibition of c-Jun N-terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats

1 Myocardial ischemia/reperfusion is associated with inflammation, apoptosis and necrosis. During this process, c-jun N-terminal kinase is activated in cardiac myocytes resulting in apoptosis. 2 This study investigates the effects of AS601245, a nonpeptide ATP competitive JNK inhibitor, on infarct size caused by myocardial ischemia/reperfusion in anaesthetized rats. The left descending coronary artery of anaesthetized rats was occluded for 30 min and then reperfused for 3 h. AS601245 was administered 5 min before the end of the ischemia period as an i.v. bolus (1.5, 4.5 or 15 mg kg(-1) i.v.) followed by continuous i.v. infusion (18, 55 and 183 microg kg(-1) min(-1), respectively) during reperfusion. Controls received saline only. 3-Aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, was used as reference compound at 10 mg kg(-1) i.v. bolus plus 0.17 mg kg(-1) min(-1) continuous infusion. 3 AS601245 significantly reduced infarct size at 4.5 mg kg(-1) (-44%; P<0.001) and 15 mg kg(-1) i.v. (-40.3%; P<0.001) similarly to 3-aminobenzamide (-44.2%; P<0.001). This protective effect was obtained without affecting hemodynamics or reducing ST-segment displacement. 4 The beneficial effects on infarct size correlated well with the reduction of c-jun phosphorylation (-85%; P<0.001 versus control) and of TUNEL-positive cells (-82.1%; P<0.001) in post-ischemic cardiomyocytes. No change in the phosphorylation state of p38 MAPK and ERK in post-ischemic heart was observed in the presence of AS601245 in comparison to the vehicle-treated group. 5 These results demonstrate that blocking the JNK pathway may represent a novel therapeutic approach for treating myocardial ischemia/reperfusion-induced cardiomyocyte death.     

Lung microvascular permeability and neutrophil recruitment are differently regulated by nitric oxide in a rat model of intestinal ischemia-reperfusion

We investigated the effect of two inhibitors of nitric oxide (NO) synthesis, N(w)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, on lung inflammation caused by intestinal ischemia/reperfusion in rats. Relative to the sham-operated rats, intestinal ischemia/reperfusion (ischemia: 45 min; reperfusion: 30 min, 2 and 4 h) induced neutrophil recruitment (increased myeloperoxidase activity) and increased microvascular permeability (Evans blue dye extravasation) in the lungs and increased tumor necrosis factor (TNF) levels in the serum (L-929 cytotoxicity assay). L-NAME given before the ischemia exacerbated neutrophil accumulation, plasma extravasation, serum TNF and caused death of the animals, which was prevented by concomitant injection of L-arginine. Lung and systemic effects of intestinal ischemia/reperfusion were not modified when L-NAME was given just before reperfusion. Treatment with aminoguanidine inhibited plasma extravasation without affecting the other parameters evaluated. Dexamethasone reduced all the parameters. Our results indicate that during intestinal ischemia/reperfusion both constitutive and inducible NO synthases are called to exert a differential modulatory effect on lung inflammation and that maintenance of adequate levels of NO during ischemia is essential for the animals survival.     

Synthesis and chemical-pharmacological characterization of the antimetastatic NAMI-A-type Ru(III) complexes (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)], (Na)[trans-RuCl4(dmso-S)(dmtp)], and [mer-RuCl3(H2O)(dmso-S)(dmtp)] (dmtp = 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine)

Ruthenium compounds have gained large interest for their potential application as chemotherapeutic agents, and in particular the complexes of the type (X)[trans-RuCl4(dmso-S)L] (X = HL or Na, NAMI-A or NAMI, respectively, for L = imidazole) are under investigation for their antimetastatic properties. The NAMI(-A)-like compounds are prodrugs that hydrolyze in vivo, and the investigation of their hydrolytic properties is therefore important for determining the nature of the potential active species. The NAMI-A-type Ru(III) complex 1, (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)] (dmtp is 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine), and the corresponding sodium analogue 2, (Na)[trans-RuCl4(dmso-S)(dmtp)], were synthesized. The hydrolyses of 1 and 2 in water as well as in buffered solutions were studied, and the first hydrolysis product, [mer-RuCl3(H2O)(dmso-S)(dmtp)].H2O (3), was isolated and characterized. The molecular structures of 1 and 3 were determined by single-crystal X-ray diffraction analyses and prove the importance of the hydrogen-bonding properties of dmtp to stabilize hydrolysis products. In vitro 1 (a) is not cytotoxic on tumor cells, following challenges from 1 to 72 h and concentrations up to 100 microM, (b) inhibits matrigel invasion at 0.1 mM and MMP-9 activity with an IC50 of about 1 mM, and (c) is devoid of pronounced effects on cell distribution among cell cycle phases. In vivo compound 1, similar to NAMI-A, significantly inhibits metastasis growth in mice bearing advanced MCa mammary carcinoma tumors. In the lungs, 1 is significantly less concentrated than NAMI-A, whereas no differences between these two compounds were found in other organs such as tumor, liver, and kidney. However, 1 caused edema and necrotic areas on liver parenchyma that are more pronounced than those caused by NAMI-A. Conversely, glomerular and tubular changes on kidney are less extensive than with NAMI-A. In conclusion, 1 confirms the excellent antimetastatic properties of this class of NAMI-A-type compounds and qualifies as an interesting alternative to NAMI-A for treating human cancers.     

The sigma<Subscript>1</Subscript> (σ<Subscript>1</Subscript>) receptor activation is a key step for the reactivation of cocaine conditioned place preference by drug priming

Rationale Cocaine-seeking behavior can be investigated in rodents using the conditioned place preference (CPP) paradigm, in which the drug-paired environment serves as a conditioned stimulus. Such approach allowed to previously demonstrate the importance of the neuromodulatory sigma₁ (₁) receptor in acquisition of cocaine-induced CPP. CPP can be extinguished and then reactivated, notably using a cocaine challenge (i.e., priming).Objectives and methods In order to examine the role of the ₁ receptor in reinstatement of Cocaine-seeking, Swiss mice acquired CPP with cocaine (30 mg/kg, ip) and then CPP was extinguished.Results A challenge cocaine priming (15 mg/kg) reactivated CPP up to 140% of the post-conditioning response. Pre-administration of the ₁ receptor antagonist BD1047 (330 mg/kg, ip) or repeated treatment with an antisense probe targeting the ₁ receptor prevented CPP reactivation. The ₁ agonist igmesine (1–10 mg/kg, ip) or the steroid dehydroepiandrosterone (DHEA, 10–40 mg/kg, sc) reactivated CPP, in a BD1047-sensitive manner. Moreover, the in vivo [³H](+)-SKF-10,047 binding levels to the ₁ receptor were increased after cocaine conditioning in numerous brain structures and these increases subsisted after extinction. Finally, cross-reactivation of cocaine-induced CPP was observed after phencyclidine (PCP), morphine, nicotine and ethanol administration. However, BD1047 blocked reactivation of CPP induced by PCP, morphine and nicotine but not ethanol.Conclusions Since activation of the ₁ receptor is not sufficient to sustain CPP in naive animals [Neuropsychopharmacology 26 (2002) 444], it is concluded that ₁ receptor activation is a key event for relapse to drug seeking. Activation may occur via sensitization due to enhanced in vivo available of receptors.     

Cyp1a1(-/-) male mice: protection against high-dose TCDD-induced lethality and wasting syndrome, and resistance to intrahepatocyte lipid accumulation and uroporphyria

To study liver toxicity and uroporphyrin (URO) accumulation and urinary excretion, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent ligand for the aryl hydrocarbon receptor (AHR), is often used as the prototype. In this study, we asked the question how important is the role of CYP1A1 in causing TCDD toxicity. Using a single large intraperitoneal dose of TCDD (200 microg/kg) and following the response over an 8-week period, we found this dose: (a) was lethal in less than 4 weeks to Cyp1a1(+/+) males but not to Cyp1a1(-/-) males or to females of either genotype; (b) caused a wasting syndrome in Cyp1a1(+/+) but not Cyp1a1(-/-) mice; (c) resulted in thymic atrophy, regardless of gender or genotype; (d) decreased spleen size and caused leukocytopenia in males but not females of either genotype; (e) caused hepatocyte hypertrophy in Cyp1a1(+/+) more so than in Cyp1a1(-/-) mice; (f) increased intrahepatocyte lipids and total liver fat content in Cyp1a1(+/+) more than Cyp1a1(-/-) males and females; and (g) caused uroporphyria in Cyp1a1(+/+) males much more than Cyp1a1(+/+) females, or in Cyp1a1(-/-) mice. Contrary to Cyp1a2(-/-) knockout mice that exhibited 15 times less accumulation of TCDD in liver than Cyp1a1/1a2(+/+) wild-type mice, Cyp1a1(-/-) mice did not show this altered TCDD distribution-indicating that CYP1A2 but not CYP1A1 is the major hepatic TCDD-binding "sink". Our data demonstrate that CYP1A1 contributes to high-dose TCDD-induced toxicity, uroporphyria, and lethality.