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Biomedical subjects

V Durlach

Publications and source records attributed to V Durlach.

At least 37 records · Page 2Linked to original sources

[Five years of DiabCare--France: assessment and outlook].

The Declaration of Saint Vincent was the starting point for the European DiabCare system. Five years of French experience with this system now provide an opportunity for critical assessment. Within the perspective of quality assurance, DiabCare is an efficient developmental tool which should eventually allow the divergence between real and ideal quality to be reduced. On the basis of a European scientific reference system, each country uses its own funds to organise national campaigns with the assistance of pharmaceutical firms. Each year a transverse collection of a month's data concerning all hospitalised diabetic patients is done at the European level by means of a standardised form. Confidential and anonymous analysis of the data is then performed by the scientific committee of DiabCare-France and the CERIM of Lille. Each participating physician receives a report specifying the situation for his group and providing anonymous comparisons with national data. This rich database offers each centre the possibility for "personalised" appraisal and retrospective evaluation of modifications in medical practices. DiabCare is in fact of interest to a variety of persons and organisations. For the patient, the DiabCare sheet and the forthcoming Diabcard (smart card) are means of providing guidance for the annual checkup. The general practitioner or specialist has indications about his patients' condition and guidance for more rigorous management. Interestingly, DiabCare is the only evaluation programme approved by general practitioner unions. For the hospital department, DiabCare provides much more detailed information than PMSI, offering a department head useful arguments in support of specific budget allocations and allowing the care team to consider its activity and determine priorities. It is a useful and precise evaluation tool for hospitals in the perspective of future accreditation. For the national and international scientific community, it provides data which, though biased by voluntary participation and non-epidemiological, are useful for analysis and comparison of particular diabetological circumstances in the field. In this respect, it is noteworthy that the World Health Organisation (WHO), the International Diabetes Federation, and the CSD have supported this initiative. For WHO, care practices and payment systems differ considerably in European countries, so that the existence of a common tool for collecting and evaluating data allows relevant procedures to be identified more quickly and communicated and recommended to the different governments. Finally, in view of the human and economic burden caused by late complications of diabetes, society can benefit. Any improvement in the control of risk factors and the objective reduction of complications is important for survival of the health care system.

Data Interpretation, Statistical↗

Evaluation of serum glycated lipoprotein(a) levels in noninsulin-dependent diabetic patients.

OBJECTIVE: Serum Lp(a) levels are generally considered unaffected by non-insulin-dependent diabetes mellitus (NIDDM). However, high Lp(a) concentrations as well as an increased rate of nonenzymatic glycation of proteins may be involved in degenerative diabetic complications. DESIGN AND METHODS: We measured serum glycated Lp(a) levels in 17 NIDDM patients, as compared to 14 normoglycaemic controls. Glycated proteins were separated from nonglycated ones by boronate affinity chromatography, and specific proteins assayed by immunonephelometric methods in both fractions. RESULTS: The percentage of glycated Lp(a) was 1.5 +/- 0.4% (mean +/- SD) in the control group, and was significantly higher in NIDDM patients: 4.3 +/- 1.5% (p < 0.01). The basal level of Lp(a) glycation was lower than that of other proteins, particularly apo B (4.0 +/- 0.7%). By contrast, the variations of glycated Lp(a) levels were of greater amplitude (+ 187%) than those of glycated apo B (+ 67%). Glycated Lp(a) values were significantly elevated in patients with micro and macrovascular complications in comparison with uncomplicated patients. CONCLUSIONS: These results suggest that glycated Lp(a) may be considered a potentially interesting parameter in the pathophysiology of diabetic vascular complications.

Adult↗

Post-prandial metabolism of triglyceride-rich lipoproteins in non-insulin-dependent diabetic patients before and after bezafibrate treatment.

Retarded post-prandial (pp) lipid clearance is potentially a major component of the increased cardiovascular risk incurred by hypertriglyceridaemic non-insulin-dependent diabetic mellitus (NIDDM) patients. The effect of bezafibrate (Bz, 400 mg per day for 5 weeks on chylomicron (CM) and remnant clearance after loads of 100 g of fat and vitamin A was therefore explored in 10 male patients (glycaemia 11.9 +/- 3.3 TG 4.5 +/- 2.4 mmol L(-1)). In all subjects CM-TG and retinyl palmitate (RP) were reduced by 50%, but 8-h non-CM (remnant) RP decreased only in initially mildly hypertriglyceridaemic subjects (-35%, P < 0.05), while in three patients with very elevated initial TG (epsilon3/3, epsilon3/2 and epsilon2/2 genotypes) 8-h remnant RP increased by 100%. The decrease in pp CM-TG correlated with that of fasting Sf 20-400 (r = 0.686, P = 0.026), suggesting that improved lipolysis was a major determinant of hypolipidaemic effect. Apo CIII synthesis is known to be depressed by Bz: concentrations were lower under Bz (P < 0.05). A positive correlation (r = 0.880, P < 0.001) with fasting TG before treatment and its disappearance after treatment suggested an involvement of high concentrations with hypertriglyceridaemia. Post-prandial non-esterified fatty acids were decreased by 35 in correlation with a significant (-19%, P < 0.05) improvement in fasting glycaemia (r = 0.801, P < 0.005). These results suggest that Bz acts both on lipolysis and on removal of CM remnants, but that removal can become saturated when lipolysis is massively improved.

Aged↗

Lipoprotein(a) isoforms display differences in affinity for plasminogen-like binding to human mononuclear cells.

Binding of lipoprotein(a) (Lp(a)) to membrane proteins of the monocyte-macrophage cell lineage may be an important event in atheroma formation. Since Lp(a) with distinct apolipoprotein(a) (apo(a)) isoforms may show differences in their affinity with regard to fibrin binding, the existence of such a functional behavior in the interaction of apo(a) in Lp(a) with these cells was explored using the monocytic cell line THP-1. Lp(a) preparations containing small size apo(a) isoforms (M(r) = 450,000 to 550,000) and high molecular mass isoforms (M(r) > or = 700,000) were purified from plasmas containing > 0.35 g/L of Lp(a) obtained from subjects (n = 14) with cardiovascular atherosclerotic disease. Binding of plasminogen to THP-1 cells was performed using the method of radioisotopic dilution. For binding of Lp(a) to cells, the THP-1 monocytic cells were incubated with varying concentrations of the different Lp(a) preparations; cells were then washed and the amount of Lp(a) bound was detected with a radiolabeled polyclonal antibody directed against apo(a). Binding due to kringle interactions with lysine residues was calculated by subtracting from the total bound the amount of Lp(a) bound (approximately 10%) in the presence of 6-aminohexanoic acid. Analysis of data with the Langmuir equation indicated identical and independent (non-interacting) sites and allowed evaluation of the Kd. Binding isotherms of small size isoforms showed saturation and a high affinity (Kd = 25.8 +/- 19 nmol/L) relative to that of plasminogen (Kd = 1750 +/- 760 nmol/L). A similar difference (Kd = 17.5 +/- 7.9 nmol/L versus Kd = 600 +/- 220 nmol/L) was found when binding experiments were performed with a fibrin surface. In contrast, binding isotherms of the high molecular mass isoforms did not show saturation at the highest Lp(a) concentrations used, thus indicating a lower affinity. In conclusion, these results show that apo(a) isoforms may display polymorphism-linked functional heterogeneity with regard to cell binding, which may explain the higher association with cardiovascular risk of small size isoforms. These qualitative differences in the binding of apo(a) isoforms to fibrin or cells may modulate the cardiovascular risk associated with high levels of Lp(a).

Adult↗

Short-term intensive insulin therapy in insulin-requiring diabetes: effectiveness and factors predicting success.

Insulin-requiring diabetes (IRD) is a condition of permanent blood glucose imbalance which occurs despite a regulated diet and treatment with maximum doses of oral anti-diabetic drugs (glibenclamide 15 mg/d + metformin 1,700 mg/d). This report describes the results of a 2-year prospective study in 75 IRD patients treated to eliminate their insulin requirement. All had residual endogenous insulin secretion (REIS) (urinary C peptide > 80 micrograms/24 h and/or basal C peptide > 2.4 ng/ml) and were treated for 10 days by subcutaneous insulin infusion via a portable pump. REIS was measured, and insulin resistance was determined by an insulin tolerance test (ITT) to define their insulin sensitivity index (DG/G) before and after 10-day intensive therapy. The patients were monitored as outpatients, and the attempt at remission was considered to be a failure (F) or a success (S). Thirty of the 75 patients (40%) were in remission at 1 year, and 14/67 (21%) at 2 years. No clinical criterion differentiated successes from failures at 1 year, nor was the initial degree of blood glucose imbalance or the REIS predictive of the metabolic changes that occurred after insulin therapy. However, the drop in the insulin requirement (IR) (-26% for F and -39% for S, p < 0.05) and the increases in the DG/G index (+68 +/- 51% for F and 176 +/- 50% for S, p < 0.01) after insulin therapy were indicative of their condition 1 year later. Receiving operating characteristic curves showed that a 35% decrease in IR and an 80% increase in DG/G were indicative of a successful outcome at 1 year, with a specificity and sensitivity of about 70%. It is concluded that a decrease in daily IR and an increase in the DG/G index during insulin treatment are prognostic indicators of the course of insulin-requiring diabetics after temporary intensive insulin treatment.

Diabetes Mellitus, Type 1↗

Neurotic, neuromuscular and autonomic nervous form of magnesium imbalance.

The nervous form of magnesium imbalance represents the best documented experimental and clinical aspects of magnesium disorders. The nervous form of primary magnesium deficit (MD) in the adult appears as the best descriptive model for analysis of the symptomatology, aetiology, physiopathology, diagnosis and therapy of the most frequent form of MD. Nervous hyperexcitability due to chronic MD in the adult results in a non-specific clinical pattern with associated central and peripheral neuromuscular symptoms, analogous to the symptomatology previously described in medical literature as latent tetany, hyperventilation syndrome, spasmophilia, chronic fatigue syndrome, neurocirculatory asthenia and idiopathic Barlow's disease. On encountering this non-specific pattern, the signs of neuromuscular hyperexcitability are of much greater importance. Trousseau's sign is less sensitive than Chvostek's sign, but their sensitivities are increased by hyperventilation (Von Bondsdorff's test). Examination of the precordial area will be conducted in order to search clinical stigmata of mitral valve prolapse (MVP) which is a frequent dyskinesia due to chronic MD (about a quarter to one-third of cases). The electromyogram (EMG) shows one (or several) trains of autorhythmic activities beating for more than 2 min of one of the three tetanic activities (uniplets, multiplets or 'complex tonicoclonic tracings') during one of the three facilitation procedures: tourniquet-induced ischaemia lasting 10 min. post-ischaemia lasting 10 min after the removal of the tourniquet and hyperventilation over 5 min. A repetitive EMG constitutes the principal mark of nervous hyperexcitability (NHE) due to MD. The echocardiogram (ECC) is the best tool for detecting MVP, the 2-dimensional ECC with pulsed Doppler being more accurate than time-motion ECC. The routine ionic investigations comprise five static tests: plasma and erythrocyte magnesium, plasma calcium and daily magnesiuria and calciuria. An evaluation of magnesium intake is desirable. Normal concentrations of magnesium in blood do not rule out the diagnosis of the nervous form of primary chronic MD. The histograms of MD group reveal Gaussian type magnesaemias with significantly lower means and the constituent elements can be individually hypo- (one-third of cases), normo- (about two-thirds of cases) and even, exceptionally, hyper-magnesaemic. The diagnosis of MD requires an oral magnesium load test. At physiological dose (5 mg of Mg/kg/day), oral magnesium is totally devoid of the pharmacological effects of parenteral magnesium. Corrections of symptomatology by this oral physiological magnesium load is the best proof that it was due to magnesium deficiency. In particular clinical forms, more sophisticated studies may be useful: standard and quantitative electroencephalograms, electropolygraphic studies of afternoon sleep, electronystagmography, optokinetic test, skin conductance reflex, psychometric inventories, standard or monitoring electrocardiogram, treadmill test, other static and dynamic investigations: e.g. ionized free Mg2+, lymphocyte Mg, brain Mg, cerebrospinal Mg, Mg balance, Mg parenteral load test, glucose load, and even radio-isotope study, the only one able to reveal intestinal magnesium hypersecretion. Nervous primary chronic MD progresses by phases of decompensation against a background of latency. Marginal magnesium deficiency, that is to say an insufficient magnesium intake which merely requires simple oral physiological supplementation, is fundamental in the aetiology of primary magnesium deficit. However a constitutional homeostatic lability of the nervous system or of magnesium metabolism such as belonging to the B35 type of HLA group must be involved. Part of the aetiology of this magnesium deficit is a magnesium depletion, where the disorder which induces magnesium deficit is related to a dysregulation of the control mechanisms of magnesium status which requires a more or less difficult

Administration, Oral↗

Dietary magnesium intake in a French adult population.

Magnesium intake was assessed using six 24-h dietary records during a 1-year period in 5,448 subjects (3,111 women 35-60 yrs old and 2,337 men 45-60 yrs old) in the SU.VI.MAX cohort, selected at a national level in France. The overall mean dietary intake was estimated at 369 +/- 106 mg/day in men and 280 +/- 84 mg/day in women. 77 per cent of women and 72 per cent of men had dietary magnesium intakes lower than recommended dietary allowances; 23 per cent of women and 18 per cent of men consumed less than 2/3 of these RDA. A strong positive correlation existed between energy and magnesium intake (r = 0.79; p < 10(-4)). Slight variations were observed according to socio-professional and educational levels and place of residence. Cereal products represented the main contribution in both men (21 per cent) and women (19.8 per cent). In men, the second source was represented by alcoholic beverages (11.7 per cent), which were a lower source of magnesium in women (5.5 per cent). Dairy products, vegetables, meat and poultry were the other main sources of dietary magnesium intake.

Adult↗

Are age-related neurodegenerative diseases linked with various types of magnesium depletion?

Age-related human neurodegenerative diseases are a major social and medical problem. It is therefore logical to take into consideration every theory with an overall approach to neurodegenerative diseases. This environmental proposal relies mainly on data concerning the Western Pacific amyotrophic lateral sclerosis-Parkinsonism-dementia complex (WP ALS-PD) considered as 'a prototypal human neurodegenerative disease' and on extrapolation from it to the bulk of neurodegenerative diseases (NDD). NDD would be due to an accelerated ageing process in certain populations of neurons due to the noxious synergy of (1) increased environmental slow deleterious factors (such as slow toxins) and of (2) decreased environmental protective factors (Mg deficient intake particularly). First, it was observed that three apparently dissimilar conditions occurred at extraordinary high rates in the Guam area: motoneuron disease (ALS), Parkinson's disease (P) and Alzheimer's-like dementia (D). Next, several other foci of endemic ALS-PD were found in Asia and Oceania in three Western Pacific population groups. These included the Chamorro people in Mariana Islands (Guam and Rota), the Auyu and Jakai people of West New Guinea and the Japanese residents of the Kii peninsula (Honshu island). The post-Second World War decline of the occurrence of WP ALS-PD in all three high incidence disease foci coupled with the absence of demonstrable heritable or transmissible factors had led to focus the search for the cause of this degenerative disease on nontransmissible environmental factors that are disappearing as the susceptible population groups acculturate to modern way. Epidemiologic study has shown that preference for traditional Chamorro food is the only one of 23 tested variables significantly associated with an increased risk for PD. An early suggestion incriminated the toxic seed of the false sago palm (Cycas circinalis L) which was used in traditional food and medicine. Laboratory investigation of cycad seed revealed the presence of various toxins and particularly of an 'unusual' non protein aminoacid: L-BMAA (beta-N-methylamino-L-alanine), an excitotoxic aminoacid. This slow toxin presents some structural similarity to another 'unusual' excitotoxic aminoacid: L-BOAA (beta-N-oxalyl-amino-L-alanine), an exogenous neurotoxin present in the grass pea (Lathyrus sativus) whose excessive consumption may cause lathyrism. The excitotoxicity of both L-BMAA and L-BOAA mainly concerns non-NMDA receptors. The neurotoxicity of these aminoacids varies with experimental models failing to induce an experimental model akin to WP ALS-PD or displaying many of the motor-system and behavioral changes of WP ALS-PD. It may be due to the presence of physiological levels of bicarbonate or of various toxic cofactors: bio-organic such as cycasin or inorganic such as pollutant metals e.g. aluminum or manganese, together with the lack of protective factors (e.g. calcium and magnesium deficiencies). Combined Al intoxication with Ca-Mg deficiencies is a reasonable model to investigate the pathogenesis of neurodegenerative diseases and eventually to screen their treatments. It may also be considered as a model of magnesium deficit, but it does not concern simple magnesium deficiency reversible with mere oral physiological magnesium supplementation. Magnesium deficiency cannot result in neurodegenerative disease. Combined Al intoxication with Ca-Mg deficiencies is not reversible through physiological oral magnesium supplementation. It therefore constitutes a type of experimental magnesium depletion model, instrumental in the investigation of the pathogenesis of magnesium depletion and in the screening of its still unknown possible treatments. (ABSTRACT TRUNCATED)

Aging↗

Postprandial cholesteryl ester transfer and high density lipoprotein composition in normotriglyceridemic non-insulin-dependent diabetic patients.

Altered postprandial HDL metabolism is a possible cause of defective reverse cholesterol transport and increased cardiovascular risk in diabetic patients with a normal fasting lipoprotein profile. Ten normolipidemic, normoponderal non-insulin dependent diabetes mellitus (NIDDM) patients and seven controls received a 980 kcal meal containing 78 g lipids with 100 000 IU vitamin A. Chylomicron clearance was not different, but area under the curve (AUC) for retinyl palmitate in chylimicron-free serum (remnant clearance) was greater in patients (P < 0.02). LCAT activity increased postprandially to the same extent in both groups. In control subjects, cholesteryl ester transfer protein (CETP) activity (CETA) also increased by 20% (P < 0.01 at 6 h) in parallel with a 20% decrease in HDL2-CE (r = -0.55, P = 0.009). In NIDDM patients, on the contrary, CETA which was 35% higher in the fasting state (P < 0.005), decreased postprandially yet HDL2-CE remained unchanged. Postprandial HDL3 of controls were enriched with phospholipid (PL) (30.3 +/- 2.6% at 6 h) with respect to fasting (25.6 +/- 2.5%, P < 0.01) and to NIDDM-HDL3 (25.8 +/- 1.7% at 6 h, P < 0.01). These results show that variation in plasma CETA has little impact on HDL2-CE in NIDDH subjects. They support the concept that, in controls, the combined enrichment of HDL3 with PL, increased LCAT and CETA create the conditions for stimulation of cell cholesterol efflux and CE transfer to apo B lipoproteins. In NIDDM, because of the lesser HDL3 enrichment with PL and of the inverse trend of CETA, these conditions fail to occur, depriving the patients of a potentially efficient mechanism of unesterified cholesterol (UC) clearance, despite their strictly normal preprandial profile.

Adult↗

The antifibrinolytic effect of lipoprotein(a) in heterozygous subjects is modulated by the relative concentration of each of the apolipoprotein(a) isoforms and their affinity for fibrin.

Individuals heterozygous for the apolipoprotein(a) [apo(a)] trait have phenotypes combining two different lipoprotein(a) [La(a)] particle suspecies that are present in plasma at a different concentration. Evaluation of the ability of each of these isoforms to bind to fibrin and affect plasminogen binding is essential to assess the pathogenic role of Lp(a) in these subjects; therefore, fractions containing different ratios of Lp(a) with distinct apo(a) isoforms (e.g. B/S3, S1/S4) were prepared by density gradient ultracentrifugation of plasma, and tested. Lp(a) fractions containing mainly small apo(a) isoforms (either B or S1) showed the highest affinity for fibrin (Kd approximately 150 nmol L-1) and the best competitor activity for plasminogen, whereas fractions containing mainly the high molecular mass isoforms (either S3 or S4) showed the lowest affinities (Kd > or = 500 nmol L-1). An increase in Kd was observed as a function of the relative content in isoforms of high molecular mass in these fractions. This inverse relationship between affinity for fibrin and apo(a) size indicates that Lp(a) subspecies in heterozygotes may have different pathogenic potential. Thus, the antifibrinolytic effect of Lp(a) in heterozygous subjects would depend on the relative concentration of the isoform with the highest affinity for fibrin.

Adult↗

Serum lipoprotein (a) concentrations in a population of 819 non-insulin-dependent diabetic patients.

Variations in serum Lp(a) concentrations were studied in a large population of non-insulin-dependent diabetic (NIDDM) patients in relation to long-term complications. Lp(a) concentrations were measured by immunonephelometry in 819 NIDDM subjects and compared with those of 128 controls. Correlations were investigated relative to plasma lipid and glycaemic parameters, body mass index (BMI) and macro- and microvascular complications. Mean absolute and relative variations of Lp(a) concentrations were studied in a subgroup of 245 patients over a one-year period. No significant differences were found between Lp(a) concentrations in NIDDM and control subjects. No relationship was evidenced with macrovascular and microvascular complications or glycaemic control. Mean relative Lp(a) variations were correlated with BMI and absolute and relative variations in triglyceridaemia. These results confirm the absence of any alterations of Lp(a) concentrations in a large cohort of NIDDM patients, either with or without micro- and macrovascular complications, but suggest a particular modulatory role for BMI and serum triglyceride variations.

Adult↗

Multiple binding with identical linkage: a mechanism that explains the effect of lipoprotein(a) on fibrinolysis.

We have previously shown that both recombinant apo(a) and native Lp(a) inhibit the binding of Glu-plasminogen to fibrin surfaces [Fleury & Anglés-Cano (1991) Biochemistry 30, 7630-7638; Rouy et al. (1992) Biochemistry 31, 6332-6339]. The aim of the present study was to characterize the mechanism of this inhibition and to define the parameters governing binding when two different Lp(a) species compete with plasminogen for fibrin, a situation that may be found in vivo in subjects heterozygous for the apo(a) trait. The Kd for the binding of plasminogen to fibrin was 660 nM whereas the affinity of Lp(a) was inversely related to apo(a) size (Kd range: 50 to > 500 nM). To determine the effect of plasminogen on Lp(a) binding and reciprocally, competition experiments were performed. The Kd of either Lp(a) or plasminogen for fibrin remained unchanged in the presence of the other competitor whereas Bmax, the maximal amount bound, was importantly decreased. In a similar fashion, competition for fibrin binding among Lp(a) isoforms was shown with the use of Lp(a) density fractions containing varying proportions of isoforms B (approximately 460 kDa) and S3 (approximately 640 kDa); variations in Kd values (from 141 nM to 460 nM) as a function of the relative content in isoform S3 were observed. Altogether, these results are indicative of multiple binding by ligands that bind with different affinities to equivalent but independent sites. Thus, in plasma from heterozygous subjects, the influence of each Lp(a) isoform on fibrinolysis will depend on their affinity for fibrin and on their concentration relative to each other and to plasminogen.

Binding, Competitive↗

Modulation of low density lipoprotein subclasses by alimentary lipemia in control and normotriglyceridemic non-insulin-dependent diabetic subjects.

Conventional factors do not fully account for the increased cardiovascular risk in NIDDM but, because of the underlying disorders in lipid metabolism, the postprandial state can be expected to induce temporary changes of a potentially atherogenic nature. The response to a 1000-kcal meal (70% lipid; 100,000 IU vitamin A) over 8 h was compared in 10 normoponderal, normotriglyceridemic NIDDM male patients and 12 controls. In patients lipolysis was normal, but remnant clearance was delayed (P < 0.02) and apo E concentrations were lower. LDL-C decreased postprandially, more in patients (P < 0.05), while LDL-PL accumulated in controls but not in patients. As a result UC:PL decreased in controls (P < 0.05) not in patients. The distribution of LDL subclasses shifted towards large particles in controls (LDL-I, 42%; LDL-II, 50%; LDL-III, 7.6% at 6 h) and smaller ones in patients (LDL-I, 29%; LDL-II, 56%; LDL-III, 16% at 6 h). In controls only, the percentage of LDL-III correlated negatively with apo E (r = -0.97, P < 0.001) suggesting that apo E promotes removal of light particles before they reach LDL-III and may be a limiting factor in patients. We conclude that the postprandial state is potentially more atherogenic in normoponderal, normotriglyceridemic patients than in controls: remnant clearance is delayed, the UC:PL ratio of LDL fails to decrease postprandially as it does in controls, limiting the acceptor capacity of LDL for UC, and the distribution of LDL subclasses is shifted towards a more atherogenic profile.

Analysis of Variance↗

Rapid and safe determination of human apolipoprotein E genotypes by miniaturised SDS-PAGE in non-insulin dependent diabetes mellitus.

AIMS: To present a non-isotopic procedure for the analysis of the different apolipoprotein E genotypes in normal subjects and patients with non-insulin dependent diabetes mellitus. METHODS: Apolipoprotein E genotypes were detected following polymerase chain reaction and miniaturised sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) (PhastSystem Pharmacia). RESULTS: The time taken from extraction of DNA from 6 microliters whole blood to the final result was eight hours. The allele frequencies in patients with diabetes mellitus in our series were similar to those found in the control subjects. CONCLUSIONS: SDS-PAGE is rapid, reliable and safe with few drawbacks, can be used as a routine procedure and may easily replace apolipoprotein E phenotyping.

Adult↗

[Post-prandial lipemia in diabetes. How? Why?].

Numerous studies show increasing evidences that a low post-prandial triglyceride metabolic capacity is likely to favour cardio-vascular disease, particularly coronary and cerebro-vascular atherosclerosis. Because of high fasting triglycerides, low HDL and high LDL3 lipid profile, abdominal obesity and insulin-resistance, Type 2 diabetic patients are candidates to altered post-prandial lipemia. However many practical and methodological difficulties remain concerning the nature, lipid quantity and composition of the lipid load, the choice of accurate markers of liver derived lipoproteins, pointing out the urgent need for a standardization procedure.

Diabetes Mellitus, Type 2↗

[Respiratory burst of neutrophils and cytokine profile in the non-insulin-dependent diabetic].

Many clinical and experimental data are in favour of a participation of leukocytes in vascular disease. Diabetes, a risk factor, is associated with a dysfunction of neutrophils. If chemotaxis and phagocytosis are deficient, it is not clearly established whether superoxide generation is conserved in these patients. We have measured this function in 35 noninsulin dependent diabetic patients, compared with a control population. We have assessed, in parallel, a profile of the cytokines involved in vascular phenomenons including TNF alpha, IL-1 beta et IL-6. Our results indicate that the generation of free radicals is normal in diabetics, with a significant elevation of TNF alpha. These results suggest a possible participation of this cytokine in the modulation of granulocyte reactivity.

Adult↗

Red blood cell magnesium concentrations: analytical problems and significance.

In order to assess total magnesium concentrations in human red blood cells (erythrocytes--ErMg), atomic absorption spectrometry (AAS) provides high accuracy and precise method rapid and amenable to automation. Taking care of eliminating the chronic marginal magnesium deficits, normal values of ErMg evaluated through a direct method and expressed as mmol/litre of packed cells are 2.3 +/- 0.24. Inductively coupled plasma-mass spectromettry (ICP-MS) is a multielemental analytical technique. Particle induced x-ray emission (PIXE) also provides multielemental capability, but is time-consuming and costly. Microelectrodes are the gold standard for intracellular Mg2+ measurements. But microelectrodes and fluorescence probes measure the activity of magnesium ions, not the concentrations. Ionized magnesium content of human intact erythrocyte is mainly assessed with the NMR method and with the zero point titration. The concentration of ionized magnesium as estimated by NMR (31P NMR method) was found to be 0.20 +/- 0.02 mmol/litre cell water and with the zero point titration 0.55 +/- 0.12. The uncertainty concerning the two current used techniques for free magnesium determination is worsened by the fact that magnesium inside red cells continually oscillates in vivo. Free magnesium constitutes a small part of total magnesium. Further studies are necessary to assess the importance of its variations in clinical medicine. Efflux of ErMg is controlled through membranous sodium-dependent and sodium-independent pathways and through genetic and neurohormonal regulations. Variations in the total or ionized ErMg do not necessarily mean that similar changes should exist in the magnesium pool. But it remains the basic static cellular magnesium item. Its value will be subsequently enhanced when it takes place among the clinical and paraclinical data of dynamic magnesium investigations.

Blood Chemical Analysis↗