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Cites a study which determines whether bone loss or fractures are associated with the presence of aortic calcifications among a large cohort of French women. Observation of lower femoral T-score and BMD in women with calcifications; Positive association of markers of bone loss and a history of fractures with the presence of vascular calcifications; Likelihood of osteoprotegerin levels to be higher among persons with fractures but not in the presence of calcifications.

Objectives: Paraoxonase-1 (PON1) detoxifies homocysteine thiolactone (HcyT) in human blood and could thus delay the development of atherosclerosis. We investigated (a) PON1 activity and polymorphisms, and (b) the relationship between PON1 activity, homocysteine (Hcy) and the severity of CAD patients in Tunisian population., Design and Methods: We used PCR-RFLP analysis to detect the Q192R and L55M variants of the PON1 gene in 100 patients with CAD and in 120 healthy controls. Paraoxonase activity was measured spectrophotometrically using phenylacetate as a substrate. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay., Results: We found an increased Hcy level in CAD patients compared to the control group (15.86+/-8.63 vs. 11.9+/-3.25 micromol/L respectively, P<0.001), and a decrease in PON1 activity in CAD patients as compared to the control group (117+/-56 vs. 181+/-73 U/mL respectively, P<0.001). PON1 Q192R and L55M polymorphisms were not associated with the presence of CAD (P=0.592, P=0.294, respectively). However, we found that PON1 activity is lower with the PON1 192RR than with PON1 192QQ genotypes in the study population. Furthermore, there were no association between PON1 L55M polymorphism and PON1 activity. We showed a significant decrease in PON1 activity in CAD patients presenting 0- to 3-vessel stenosis (155+/-39; 135+/-36; 103+/-22; 77+/-24 U/mL, respectively; P<0.001)., Conclusion: In this study, we showed that low PON1 activity is associated with the PON1 192RR genotypes and associated with the severity of CAD in the Tunisian population. We hypothesize that high level of Hcy together with low PON1 activity results in an increased plasma HcyT plasma concentration leading to protein N-homocysteinylation and the development and progression of atherosclerosis.

Background: Hyperhomocysteinaemia is an independent, graded risk factor for coronary artery disease (CAD). The methylenetetrahydrofolate reductase (MTHFR) polymorphism is associated with hyperhomcysteinaemia and may therefore influence individual susceptibility to CAD. We have investigated this risk factor in a Tunisian Arab population., Methods: Polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect the C677T and A1298C variants of the MTHFR gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed as the number of affected vessels. Plasma total homocysteine (tHcy) concentration was determined using a direct chemiluminescence assay., Results: MTHFR CC, CT and TT genotype frequencies in the CAD group were significantly different from those observed in the control group (49%, 35% and 16% versus 48.3%, 45.8% and 5.8%, respectively; P = 0.031). However, MTHFR AA, AC and CC genotypes frequencies in the CAD group were not significantly different from the control group ( P = 0.568). Patients with CAD showed higher plasma tHcy concentrations than patients without CAD (15.86 +/- 8.63 micromol/L versus 11.90 +/- 3.25 micromol/L, P < 0.001). There was no association between the MTHFR polymorphisms and the number of stenosed vessels. Patients with the MTHFR TT genotype had higher plasma tHcy, serum creatinine, cholesterol and triglyceride concentrations than patients with the MTHFR CC genotype., Conclusions: The C677T polymorphism of the MTHFR gene is associated with hyperhomocysteinaemia, lipid dysregulation and the presence of CAD in this Tunisian Arab population.

Background: Hyperhomocysteinemia is an independent, graded risk factor for coronary artery disease (CAD). The G894T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia and could influence individual susceptibility to CAD. The aims of this study were to investigate (a) the relationship of the eNOS G894T polymorphism with the presence and the severity of CAD and (b) the possible relationship between hyperhomocysteinemia and the eNOS G894T variant for the risk of CAD severity in a Tunisian population., Methods: We used PCR with restriction fragment length polymorphism analysis to detect the G894T variant of the eNOS gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed by the number of affected vessels. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay., Results: The frequencies of the eNOS GG, GT, and TT genotypes in the CAD group were significantly different from those in the control group (45%, 44%, and 11% vs 60%, 35.8% and 4.2%, respectively; P = 0.035). There was no association between the eNOS G894T genotype frequencies and the number of stenosed vessels (P = 0.149). In the CAD group, the coexistence of the 894 GT or TT genotypes and hyperhomocysteinemia led to an increased risk of CAD severity., Conclusion: The G894T polymorphism of the eNOS gene is associated with the presence of CAD, and in conjunction with hyperhomocysteinemia, increased the risk of CAD severity in a Tunisian population.

Objective: Cardiopulmonary bypass (CPB) is known to cause part of the systemic inflammatory reaction after cardiac surgery that can be responsible for organ failure. A novel technique based on a minimal extracorporeal circulation (MECC(R)) system has been evaluated with regard to the inflammatory response in a prospective study involving patients undergoing coronary artery bypass grafting., Methods: Sixty consecutive patients were randomly assigned to either standard normothermic CPB (n=30) or the MECC system, with a reduced priming volume, no aortic venting and no venous reservoir, excluding the blood-air interface (n=30). Specific evaluation of cytokine release (IL-1beta, IL-6, TNF-alpha), as well as neutrophil elastase secretion and beta-thromboglobulin release from platelets and S100 protein assay were performed. Serial blood samples were taken prior to the onset, after initiation, at the end and after weaning of the CPB; further samples were collected 6 and 24h after the end of the CPB., Results: All patients were similar with regards to pre- and intra-operative characteristics and clinical outcomes were comparable for both groups. MECC system allowed a reduced hemodilution with a mean drop of the hematocrit of 8.5 vs. 15.3% (P<0.05). Mononuclear phagocytes dropped in a more important manner under standard CPB conditions (247+/-151 vs. 419+/-168, P=0.002), but both groups demonstrated a rise in monocyte count at the end of the CBP. No significant release of IL-1beta was observed in either group. By the end of CPB, IL-6 levels were significantly lower in the MECC group (38.8+/-19.6 vs. 87.9+/-78.9, P=0.04), despite a higher monocyte count. Plasma levels of TNF-alpha rised significantly more during standard CPB than with the MECC system (17.8+/-15.4 vs. 10.1+/-5.6, P=0.002). With MECC, the neutrophil elastase release was reduced (72.7+/-47.9 vs. 219.6+/-103.4, P=0.001). Platelet count remained at higher values with the minimal compared to standard CPB. It is noteworthy to consider that beta-thromboglobulin levels showed slightly lower platelet activation in the MECC group at all times of CPB (110.5+/-55.6 vs. 134.7+/-46.8, P=0.10). The pattern of release of S100 protein showed higher values in patients undergoing standard CPB than after MECC., Conclusions: The MECC system is suitable to maintain total extracorporeal circulation and demonstrates a lower inflammatory reaction when compared to standard CPB.

Pheochromocytoma and neuroblastoma are distinct tumours, but their biological diagnosis is based on secretion increase of one or several catecholamines. Assays have to be very sensible and specific for an early diagnosis. 24 hours urinary catecholamines and metabolites are currently measured, but technical improvements permit plasma metanephrine assay, an excellent indicator of pheochromocytoma. HPLC coupled to electrochemical detection represents the most efficient methodology. After a review of urinary and plasma assay methods, the authors show usual values of catecholamines, metanephrines, HVA and VMA, according to ages, and give examples of results encountered in classical or not tumours and in falsely positive cases. Urinary metanephrine assay is the most sensible and specific in biological diagnosis of pheochromocytoma, while catecholamines and VMA assays lack of sensibility. Results have to be given by 24 hours and by creatinine ratio. Metanephrine assay can be performed also in plasma and exhibits the same interest. However, in urine as in plasma, in case of renal failure, results cannot be interpreted. Neuroblastoma biological diagnosis is based classically on HVA, VMA, and dopamine assays, nowadays only in 24 hours urine (or in urinary micturition for screening), and results are also expressed as creatinine ratio. But even if several assays are advisable, 5% of the neuroblastoma cases do not produce increased catecholamine values. In some cases, metanephrine assay could be of interest. After the age of 12 months, clinical expression of neuroblastoma is dramatic in 70% of cases. So, a biological screening has been experimented in several countries including France. A French translation of the consensus conference report (1998) is appended, which shows the complexity of neuroblastoma screening. Now, there is no evidence that early tumour detection by screening lessens the mortality rate, but a weak benefit is not excluded.

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.

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.

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.

When diabetes has been diagnosed, its classification into different types is traditionally carried out according to clinical criteria. But with arising of new parameters, one of which is C-peptide, and various subtypes of diabetes, it became more difficult. So, in order to improve the accuracy of the classification, 270 diabetic patients and 269 controls, all black senegalese subjects, were submitted to a two-step oral glucose tolerance test (0 and 120 min.) with determination of plasma glucose and C-peptide concentrations. The majority of NIDDM were confirmed at the opposite of IDDM; furthermore, it has been pointed out a group corresponding with impaired glucose tolerance (IGT) among the initial controls. When comparing the two classification modes, before and after plasma C-peptide determination, it appeared statistically significant differences with p values of 10(-4) for both IDDM and NIDDM.

At the opposite of HLA-DR, HLA-DQ was not well documented in homogeneous negroïd populations. So, 93 IDDM and 115 control patients, all black senegalese people, were studied. The results showed three HLA-DQ IDDM-related susceptibility genotypes and also a high risk conferred by HLA-DR4/DR9 usually described in Mongoloïd people. Furthermore, DR:DQ associations allowed the identification of three IDDM predisposition genotypes, each of them with a characteristic mean age for disease diagnosis.

The measurement of plasma amino acid concentrations (50 samples) by gas-chromatography and by ion-exchange chromatography (IEC) indicates that the two methods correlate well. However, IEC provides higher values for proline, threonine and serine. The results are confirmed by the study of normal values obtained in healthy subjects.

Administration of phenobarbital, a known inducer of glutathione S-transferase activity in rat liver, failed to stimulate sulfobromophthalein (BSP) conjugation by liver cytosol in hamsters. The latter displayed poor ability to conjugate this substrate, despite very high glutathione-conjugating activity with the broad-spectrum substrate 1-chloro-2,4-dinitrobenzene (CDNB). Of the six substrates tested, in this species, 1,2-epoxy-3-(4-nitrophenoxy)propane (ENPP) was the only one whose conjugation was greatly enhanced by phenobarbital (+172%). Nevertheless, hamsters proved as responsive to phenobarbital induction as rats, since it increased their relative liver weight and microsomal enzyme activity. The deficient induction of liver BSP-conjugating activity observed with phenobarbital is consistent with the finding that it did not affect the hepatic transport of this substrate in hamsters.