The MAO-B inhibitor deprenyl, but not the MAO-A inhibitor clorgyline, potentiates the neurotoxicity ofp-chloroamphetamine

The effect of co-administration of MAO inhibitors together with a low dose of the neurotoxic amphetaminep-chloroamphetamine (pCA) on neurotoxicity was examined. Neurotoxicity was assessed by measuring decreases in the binding of [³H]cyanoimipramine to serotonin uptake sites using quantitative autoradiography. By itself, a low dose of pCA (2 mg/kg) did not produce any alterations in radioligand binding, measured 7 days after drug administration. However, co-administration of the MAO-B selective inhibitor deprenyl (1 mg/kg) or the non-selective inhibitor pargyline (50 mg/kg) produced significant ecreases in radioligand binding. Measurements of the effects of these drugs on body temperature ruled out the possibility that deprenyl and pargyline were increasing neurotoxicity by producing a drug-induced hyperthermia. In contrast to the effects of deprenyl and pargyline, co-administration of the MAO-A selective inhibitor clorgyline (1 mg/kg) did not alter binding. By themselves none of the MAO inhibitors produced neurotoxic effects. There are a number of possible explanations for these results. Administration of deprenyl or pargyline, together with pCA, itself a MAO-A inhibitor, will lead to inhibition of both MAO-A and MAO-B activities. This will likely lead to an enhanced release of dopamine and serotonin compared with the release following administration of pCA alone or pCA together with clorgyline. Elevation of the extracellular levels of either or both of these monoamines could lead to enhanced neurotoxicity. Whatever the mechanism involved, our results show that the co-administration of a type-B MAOI enhances the neurotoxic effects of pCA on serotonin neurons.     

Prevalence of coeliac disease in diabetic children and their first-degree relatives in West Algeria: screening with serological markers

Atypical and relatively silent forms of coeliac disease (CD) have been described in insulin-dependent diabetes mellitus (IDDM). Our aim was to evaluate the prevalence of CD-IDDM with serological markers and to investigate the presence of CD in the IDDM first-degree relatives. During 1993 94 we explored 116 IDDM patients reported as new cases and 381 first-degree relatives of IDDM patients. Determination of IgA and IgG antigliadin antibodies (AGA) and IgA antiendomysium antibodies (AEA) was made. Jejunal biopsy was performed in symptomatic patients or in those with positive serological markers, (i) Nineteen IDDM-CD were identified and 5 were suspected. Thus, the prevalence of CD in IDDM patients was between 16.4 and 20%. AGA and/or AEA were abnormal in 13 and normal in 5. Sensitivity was 80% for the three tests when used simultaneously and specificity was 100%. (ii) In the family study, 26 sera of asymptomatic first-degree relatives of IDDM patients were positive for at least one of the serological markers; 13 of them had villous atrophy. Systematic serological screening in IDDM allowed us to detect CD and evaluate the true incidence.     

5' ins/del and 3' VNTR polymorphisms in the apolipoprotein B gene in relation to lipids and coronary artery disease.

BACKGROUND: Studies that considered apolipoprotein B (APOB) gene polymorphisms as risk factors for coronary artery disease (CAD) have reported conflicting results. We sought to analyze the association between 5' ins/del and 3' VNTR polymorphisms of APOB, lipid parameters and CAD risk. METHODS: We recruited 251 patients with CAD, documented by coronary angiography, and 94 controls. Genotyping was performed by PCR. Lipids and apolipoproteins were measured. RESULTS: 5' ins/del (ins/ins, ins/del, del/del) and 3' VNTR (LL, SS, LS) polymorphism frequencies were significantly (p<0.05) different between controls and CAD patients. LL and del/del were significantly associated with higher levels of apolipoprotein B (apoB), total cholesterol/high-density lipoprotein cholesterol ratio and apoB/apoA-I ratio (p<0.05) and with increased risk of CAD. The odds ratio for significant coronary stenosis associated with del/del was 3.2 (95% CI 1.6-36.42) (p=0.032) and with LL was 2.2 (95% CI 1.1-5.1) (p=0.042). CONCLUSIONS: The two polymorphisms exert an impact on lipid levels and contribute to the susceptibility to the development of CAD.     

Argan oil improves surrogate markers of CVD in humans

Limited - though increasing - evidence suggests that argan oil might be endowed with potential healthful properties, mostly in the areas of CVD and prostate cancer. We sought to comprehensively determine the effects of argan oil supplementation on the plasma lipid profile and antioxidant status of a group of healthy Algerian subjects, compared with matched controls. A total of twenty healthy subjects consumed 15 g/d of argan oil - with toasted bread - for breakfast, during 4 weeks (intervention group), whereas twenty matched controls followed their habitual diet, but did not consume argan oil. The study lasted 30 d. At the end of the study, argan oil-supplemented subjects exhibited higher plasma vitamin E concentrations, lower total and LDL-cholesterol, lower TAG and improved plasma and cellular antioxidant profile, when compared with controls. In conclusion, we showed that Algerian argan oil is able to positively modulate some surrogate markers of CVD, through mechanisms which warrant further investigation.     

Rapid sequence evolution of street rabies glycoprotein is related to the highly heterogeneous nature of the viral population.

The sequence of the glycoprotein gene of a street rabies virus was determined directly using fragments of a rabid dog brain after PCR amplification. Compared with that of the prototype strain CVS, this sequence displayed 10% divergence in overall amino acid composition. However only 6% divergence was noted in the ectodomain suggesting that structural constraints are exerted on this portion of the glycoprotein. A human strain isolated on cell culture from the saliva of a patient with clinical rabies had only five amino acid differences with the canine isolate, an indication of their close relatedness. These differences could have originated during transmission from dog to dog, or from dog to man, or during isolation on cell culture; they are nonetheless indicative of a genetic evolution of street rabies virus. This evolution was further evidenced by the selection of cell-adapted variants which displayed new amino acid substitutions in the glycoprotein. One of them concerned antigenic site III where arginine at position 333 was replaced by glutamine. As expected this substitution conferred resistance to a site IIIa monoclonal antibody (MAb), but surprisingly did not abolish neurovirulence for adult mice. However, a decrease in the neurovirulence of the cell-adapted variant in the presence of a site IIIa specific MAb was noted, suggesting that neurovirulence was due to a subpopulation neutralizable by the MAb. Simultaneous presence of both the parental and variant sequences was indeed evidenced in the brain of a mouse inoculated with the cell-adapted variant; during multiplication in the mouse brain, the frequency of the parental sequence rose from less than 10% to nearly 50%, indicating the selective advantage conferred by arginine 333 in nervous tissue. Altogether these results were suggestive of an intrinsic heterogeneity of street rabies virus. This heterogeneity was further demonstrated by the sequencing of molecular clones of the glycoprotein gene, which revealed that only one-third of the viral genomes present in the brain of a rabid dog had the consensus sequence. Two-thirds of the clones analyzed displayed from one to three amino acid substitutions. Such heterogeneous populations have been referred to as quasispecies, a concept which implies heterogeneous populations kept together in a dynamic equilibrium. This equilibrium could be rapidly displaced, giving the virus the capacity to adapt easily to new environmental conditions.     

Impairment of left and right ventricular longitudinal strain in asymptomatic children with type 1 diabetes

AimThe relationship between type 1 diabetes (T1DM) and cardiac function in children is not well established. The purpose of this study was to investigate whether children and adolescents with T1DM present early asymptomatic abnormalities of left ventricular (LV) and right ventricular (RV) function. In addition, we evaluated the relationship of any such abnormalities with glycemic control and diabetes duration.MethodsThis was a prospective study. Standard echocardiography, tissue Doppler imaging, and two-dimensional strain analysis were performed prospectively in 52 children with T1DM. The results were compared with those from 52 healthy children matched for age and sex.ResultsThere were no significant differences between the two groups in LV ejection fraction or RV systolic function. There was a difference between the two study groups in transtricuspid flow: the E-wave and A-wave velocities were significantly higher in the diabetic group. Left ventricular global longitudinal strain (LV GLS) was significantly lower in children with T1DM (?20.01 ± 1.86% vs. ?22.99 ± 0.98%, respectively; P < .001), as was RV free-wall longitudinal strain (RV FWLS) (?29.13 ± 1.85% vs. ?30.22 ± 1.53%, respectively; P = .002). LV GLS was correlated with diabetes duration (r = 0.444, P < .001) and glycated hemoglobin (HbA1c) (r = 0.683, P < .001); however, no correlation was found between RV FWLS and HbA1c or diabetes duration.ConclusionsOur findings suggest that LV GLS and RV FWLS are impaired in children with T1DM and that the decrease in LV GLS is correlated with diabetes duration and HbA1c levels.