The cholecystocolic bypass with jejunal interposition graft for bile acid depletion in bile and portal blood in guinea pigs.

Ileal bypass and cholecystostomy are used in children with selected cholestatic diseases to lower the bile acid (BA) levels in bile and blood and improve outcome. The efficacy of a cholecystocolic bypass in achieving the same goals was investigated in guinea pigs. In the study group (n=7), a cholecystocolic bypass was performed using a jejunal graft interposed between the gallbladder and the cecum. In the control group (n=5), a cholecystojejunal bypass was performed with a similar graft implanted in the proximal jejunum. Total BA concentration was measured in bile and portal blood at surgery (D0) and 30 days later (D30) by pooling the concentrations of 7 individual BA. D30/D0 BA ratios were compared. All animals developed normally without clinical symptoms. A 76% reduction in the bile T-BA levels was observed in both groups (p<0.05). A 80% decrease of T-BA levels was observed in portal vein in study group (p<0.05), suggesting that ileal bile flow and BA ileal reabsorption were highly impaired. No change in portal vein BA levels was observed in control group. Cholecystocolic bypass led to a significant loss of bile acids in guinea pigs and might be considered for bile diversion in pediatric patients with selected cholestatic diseases.

[Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal]. / Polymorphisme génétique de pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2) et fatty acid binding protein (FABP2) chez la population diabétique du Sénégal.

We reported a study about three candidate genes which may be involved in non-insulin dependent diabetes mellitus (NIDDM): Pyruvate Dehydrogenase Kinase 4 (PDK4), Paraoxonase 2 (PON2) and Fatty Acid Binding Protein 2 (FABP2). The reported mutation in the three candidate genes were tested for 179 black subjects from Dakar (Sénégal) by PCR-RFLP techniques. There was no significant difference between both control and NIDDM subjects. The genotype frequency in the senegalese population was quite similar as compared to reported frequency in white populations excepted for PDK4 polymorphism. These results suggest that none of these gene variants is a major NIDDM predisposing locus for the negroid population of Senegal.

Iron metabolism, free radicals, and oxidative injury.

Iron has the capacity to accept and donate electrons readily. This capability makes it physiologically essential, as a useful component of cytochromes and oxygen-binding molecules. However, iron is also biochemically dangerous; it can damage tissues by catalyzing the conversion of hydrogen peroxide to free-radical ions that attack cellular membranes, protein and DNA. This threat is reduced in the healthy state where, because of the fine iron metabolism regulation, there is never appreciable concentration of 'free iron'. Under pathological conditions, iron metabolism and superoxide metabolism are clearly interactive. Each can exacerbate the toxicity of the other. Iron overload may amplify the damaging effects of superoxide overproduction in a very broad spectrum of inflammatory, both acute and chronic, conditions. Furthermore, chronic oxidative stress may modulate iron uptake and storage, leading to a self-sustained and ever-increasing spiral of cytotoxic and mutagenic events. The iron chelator deferroxamine is able to chelate 'free iron' even inside the cell. Its regular clinical use is to promote the excretion of an iron overload, when phlebotomy is harmful, and the dosage varies between 2-10 g/d. In conditions where deferroxamine is used to prevent the iron-driven oxygen toxicity, i.e., acute or chronic inflammatory diseases with oxidative stress, the dosage can be extremely reduced and the addition of antioxidants could be useful.

Does warm antegrade intermittent blood cardioplegia really protect the heart during coronary surgery?

OBJECTIVE: Intermittent antegrade blood cardioplegia (IABC) has been standardized as a routine technique for myocardial protection in coronary surgery. However, if the myocardium is known to tolerate short periods of ischemia during hypothermic arrest, it may be less tolerant of warm ischemia, so the optimal cardioplegic temperature of intermittent antegrade blood cardioplegia is still controversial. The aim of this study was to compare the effects of warm intermittent antegrade blood cardioplegia and cold intermittent antegrade blood cardioplegia on myocardial pH and different parameters of the myocardial metabolism. METHODS: Thirty patients undergoing first-time isolated coronary surgery were randomly allocated into two groups: group 1 (15 patients) received warm (37 degrees C) intermittent antegrade blood cardioplegia and group 2 (15 patients) received cold (4 degrees C) intermittent antegrade blood cardioplegia. The two randomization groups had similar demographic and angiographic characteristics. Total duration of cardiopulmonary bypass (108+/-17 and 98+/-21 min) and of aortic cross-clamping (70+/-13 and 65+/-15 min) were similar. The cardioplegic solutions were prepared by mixing blood with potassium and infused at a flow rate of 250 ml/min for a concentration of 20 mEq/l during 2 min after each anastomosis or after 15 min of ischemia. Intramyocardial pH was continuously measured during cardioplegic arrest by a miniature glass electrode and values were corrected by temperature. Myocardial metabolism was assessed before aortic clamping (pre-XCL), 1 min after removal of the clamp (XCL off) and 15 min after reperfusion (Rep) by collecting coronary sinus blood samples. All samples were analyzed for lactate, creatine kinase (MB fraction), myoglobin and troponin I. Creatine kinase and troponin I were also daily evaluated in peripheral blood during 6 days post-operatively. RESULTS: The clinical outcomes and the haemodynamic parameters between the two groups were identical. In group 1, XCL off and Rep were associated with higher coronary sinus release of lactate (5.5 +/- 1.8 and 2.2 +/- 0.5 mmol/l) than in group 2 (2.0 +/- 0.7 and 1.6 +/- 0.3 mmol/l, P < 0.05). Mean intramyocardial pH was lower in group 1 (7.23 +/- 0.08) than in group 2 (7.65 +/- 0.30, P < 0.05). There were no significant differences between the two groups with respect of creatine kinase (MB fraction) either after Rep or during the post-operative period. Lower coronary sinus release of myoglobin was detected at Rep in group 1 (170 +/- 53 microg/l) than in group 2 (240 +/- 95 microg/l, P < 0.05). At day 1, a lower release of troponin I was found in group 1 (0.11 +/- 0.07 g/ml) compared to group 2 (0.17 +/- 0.07 ng/ml, P < 0.05). CONCLUSION: With regards to similar clinical and haemodynamic results, myocardial protection induced by warm IAEX is associated with more acidic conditions (intramyocardial pH and lactate release) and less myocardial injury (myoglobin and troponin I release) than cold intermittent antegrade blood cardioplegia during coronary surgery.

[Effect of "micronized" C60 fullerene on the microbial growth in vitro]. / Effet du fullerène C60 "micronisé" sur la croissance microbienne in vitro.

The effect of C60 "micronized fullerene was tested by a manual and automatised (Analyzer Bioscreen C(R)) micromethod on the microbial growth of 22 collection strains: E. coli (5), P. aeruginosa (2), S. Typhimurium (6), S. aureus (2), L. monocytogenes (2), E. hirae (1), B. cereus (1), B. subtilis (1), B. pumilus (1) et C. albicans (1). No effect on microbial growth was observed with C60 "micronized fullerene (43.2 microg/ml) on all strains studied: no difference was found with doubling time, slope and growth rate constant. The results of cytotoxicity obtained with animal models or in vitro cultures as human monocyte, leukocyte or macrophage confirm the absence of effect of C60 fullerene at a concentration compatible with microbial or biological models. This study is included in research program headed "Therapeutics perspectives of fullerenes.

A review of myocardial normothermia: its theoretical basis and the potential clinical benefits in cardiac surgery.

Myocardial protection during cardiac surgery aims to preserve myocardial function while providing a bloodless and motionless operating field to make surgery easier. Myocardial protection is achieved by decreasing the oxygen needs using hypothermia and producing electromechanical cardiac arrest using potassium infusion which allows surgery to be performed on a non-beating heart. The deleterious effects of hypothermia include dysfunction of enzymatic systems, development of acidosis, a decrease in tissue oxygen delivery, an increase in blood viscosity and a decrease in erythrocyte deformability. Ninety percent of the decrease in oxygen consumption is obtained by inducing electromechanical arrest and inducing hypothermia has little additional benefit. Maintenance of systemic and myocardial normothermia reduces problems and provides a more physiological approach for cardiopulmonary bypass (CPB). The current results obtained using normothermic protection are very encouraging, and it is an easier inexpensive option. This review summarizes the current knowledge on the benefits of normothermia, based upon experimental and clinical studies.

Insulin assays and reference values.

Insulin is produced by beta cells in pancreatic islets of Langherans via a complex process of proteolytic conversion. A precursor molecule, proinsulin, is transported to the Golgi apparatus where it is packed into secretory granules. Maturation of the secretory granules is associated with conversion of proinsulin to insulin and C-peptide by enzymatic cleavage. Secretion of insulin into the bloodstream is accompanied by the release of small amounts of proinsulins. Insulin immunoassays consist of radioimmunoassays using polyclonal antisera which cross-react with proinsulins, and two-site assays using monoclonal antibodies. These immunometric assays have led to improvements in specificity and sensitivity as compared to radioimmunoassays. To determine reference values and limits, insulinaemia must be measured in normoglycaemic subjects with a normal body weight. Moreover, as insulinaemia is most often measured during stimulation tests, reference values must also be determined for the most common tests such as the oral glucose tolerance test or the intravenous glucose tolerance test. We report the analytical characteristics of insulin assays and review reference values and their interpretation. Wide-scale use of insulin assays remains a subject of research rather than a diagnostic application. Spontaneous hypoglycaemia, a disorder which can be caused by hyperinsulinism, insulinoma, insulin autoimmune syndrome and non-insulin-mediated factors, is almost the only clinical indication for the measurement of plasma insulin. Diabetes is diagnosed solely on the basis of chronic hyperglycaemia. Thus, measurement of plasma insulin has no clinical value in the diagnosis or management of diabetic patients, with the exception of rare cases including the syndrome of severe insulin resistance and abnormalities in beta-cell secretory products. Otherwise, insulin measurement is used in experimental investigations to study the pathophysiology of various disorders, especially diabetes. The reference and range of plasma insulin values are not yet clearly established, and the range of concentrations reported in the literature remains unsatisfactory. There is a need to standardise results and thereby improve comparability among studies.

[HLA-markers and diabetic retinopathy in the Senegalese population]. / Marqueurs HLA et rétinopathie diabétique dans la population Sénégalaise.

Patients with IDDM often develop severe forms of retinopathy, supposed to be associated to risk factors such as hypertension, poor glycemic control and nephropathy. A controversial intervention of a genetic marker was evoked so as some diabetic patients have retinopathy in the absence of known risk factors. HLA-DR and DQ markers were compared in two groups of patients with IDDM respectively constituted of patients with and without severe retinopathy. HLA typing was carried out by polymerase chain reaction (PCR) and restriction fragments of length polymorphism (RFLP). DR9 (p < 10(-4); O.R. = 8.36) and DQA1*0301 (p < 0.05; O.R = 2.92) alleles were positively associated to diabetic retinopathy, at the opposite of DR3 (p < 10(-3); O.R: 0.01) and DQA1* (p < 10(-9); O.R = 0.15). Furthermore, among the genotypes previously considered as risk markers of IDDM in senegalese people, only DR4: DQA1*0301:DQB1*0302/DR9: DQA1*0301: DQB1*0201 was often observed in retinopathy.

[Insulin-dependent diabetes in Senegal: HLA-DR combinations according to age of onset and sex]. / Le diabète insulino-dépendant en milieu Sénégalais: combinaisons HLA-DR en fonction de l'âge d'installation et du sexe.

In insulin-dependent diabetes mellitus, HLA-DR markers are involved, namely DR3, DR4 and DR9 alleles, among black senegalese populations. Studying the different associations of these alleles showed a strong predisposition to insulin-dependent diabetes mellitus with DR3/4 (p > 10(-2); OR = 13.6); DR4/9 (p < 10(-2); OR = 8.32) and DR9/9 (p < 0.05; OR = 7.78). And then it was observed a tendency to an inverse relationship of DR3/4 frequency with age of onset in male patients.

[Role of Maillard products in the chronic complications of diabetes mellitus. Bioclinical applications]. / Rôle des produits de Maillard dans les complications chroniques du diabète sucré. Applications biocliniques.

The formation of Maillard products is increased in the diabetes mellitus. These advanced glycated end products (AGEs) alter metabolic functions of macromolecules and increase free radical formation while decreasing free radical-scavenging enzyme activity. The elimination of AGEs is insured by the macrophage cells equipped with appropriate receptors (RAGE) and cleared by kidneys. The knowledge of these molecular mechanisms had allowed the emergence of biochemical analytes such as 3-deoxyglucosone, pentosidine, and carboxymethyl-lysine, as markers of the ris of micro- and macro-angiopathy, the main chronic complications of the diabetes mellitus.