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Biomedical subjects

P Drouin

Publications and source records attributed to P Drouin.

At least 19 recordsLinked to original sources
PubMed1996

Role of albumin glycation on the erythrocyte aggregation: an in vitro study.

The increased erythrocyte aggregation observed in diabetes mellitus is mainly due to changes in the balance between aggregating factors and anti-aggregating ones, like albumin. Since chronic hyperglycaemia results in protein glycation, we examined the effect of in vitro glycation of albumin on its anti-aggregating role with blood from 29 Type 1 diabetic patients and 29 healthy controls. After the addition of glycated and unglycated albumin, samples had a glycation level of 24% for healthy controls and 28% for diabetic patients. Erythrocyte aggregation was determined by the analysis of the light backscattered by a blood suspension. Erythrocytes from healthy controls suspended in glycated albumin had significantly higher rates of rouleaux formation (p < 0.01) than in unglycated albumin and increased cohesion of rouleaux (p < 0.05). The erythrocyte aggregation in diabetic patients underwent similar changes (p < 0.01). The time-resolved fluorescence of the single tryptophan residue was monitored to describe the changes in the conformational equilibrium of albumin. The lifetime data showed that the increases in the two lifetime components and in the relative proportion of the major lifetime are in agreement with a conformational change in albumin after glycation. Thus, the changes in albumin conformation could be responsible for the smaller hypoaggregating effect of glycated albumin.

Adult↗
PubMed1996

Multiorgan fatal chronic complications following radiation treatment for cancer of the cervix--results of fibroblast assay.

We report a case of severe chronic normal tissue injury following conventional irradiation in a 33-year-old patient with a strong family history of cancer. Her cultured fibroblasts exhibited a response to low-dose-rate irradiation similar to fibroblasts taken from a normal individual. For acute irradiation her fibroblasts showed a slight increased sensitivity to single doses compared to fibroblasts from a normal individual. This difference was much larger when fractionated irradiation was given. It is concluded that the hypersensitive response of this patient was due to the fractionated radiotherapy and not to the low-dose-rate brachytherapy. We believe that this is the first report of this form of cellular radiosensitivity which is mainly expressed in fractionated radiotherapy.

Adult↗
PubMed1996

Apo B-containing lipoprotein particles in poorly controlled insulin-dependent diabetes.

The goal of this study was to compare the structural and biological characteristics of apolipoprotein (apo) B-100-containing particle subfractions isolated from poorly controlled diabetic patients with insulin-dependent diabetes (IDDM), and healthy controls matched for sex, age and body mass index (BMI). Different apo B-containing particles were isolated by sequential immunochromatography and were free of apo A-I, apo A-II, apo A-IV and apo(a). Particles lipoprotein (Lp) B/C-III contained apo B and apo C-III. They were free of apo E. Particles Lp B/E contained apo B and apo E. They were free of apo C-III. Particles Lp B were devoided of apo C-III and apo E. All these particles could contain other known apolipoproteins not cited here, as for example apo C-II and/or apo C-I. The plasma levels of cholesterol, triglycerides, phospholipids, apo A-I, B-100, C-III, E, total Lp B/C-III, total Lp B/E were not different between patients and controls. The physico-chemical properties of Lp B/C-III and Lp B/E were similar in both groups. Only Lp B from patients exhibited some changes, an increase in the size and a decrease in the cholesterol and cholesteryl ester levels. The conformational properties of the lipoproteins were studied through their immunoreactivity against four different anti-apo B-100 monoclonal antibodies (MAb) for which sequential epitopes have been located on the protein, and one MAb for which the epitope is conformationally expressed. Again, minor changes were observed between patients and controls, and only a slight decrease in the immunoreactivity of the epitope encompassing amino-acid residues 405 to 539 of Lp B and of the conformationally expressed epitope of Lp B/C-III were found in patients. Nevertheless, whatever these conformational and/or physico-chemical modifications may be, they were not sufficient to induce functional alterations in the binding of the particles from the patients to the LDL-receptor of HeLa cells. This study shows that IDDM is not associated with any significant abnormalities in the apo-containing lipoprotein particles. The excessive occurrence of coronary heart disease (CHD) and other atherosclerotic vascular disease in patients with IDDM must have other causes.

Adult↗
PubMed1996

Intraperitoneal insulin infusion improves the depletion in choline-containing phospholipids of lipoprotein B particles in type I diabetic patients.

Insulin-dependent diabetes mellitus (IDDM) is characterized by altered composition of atherogenic lipoproteins, especially a depletion in choline-containing phospholipids (PL) of apolipoprotein (apo) B lipoproteins (LpB). To determine the effects of continuous intraperitoneal (IP) insulin infusion (CIPII) on this qualitative lipoprotein abnormality, we compared lipoprotein profiles of 14 IDDM patients treated by continuous subcutaneous insulin infusion (CSII) and at 2 and 4 months after treatment with CIPII using an implantable pump. IDDM patients were in fair metabolic control and were compared with 14 healthy control subjects matched for sex, age, body mass index, and plasma lipids. The following parameters were studies: hemoglobin A1c (HbA1c), monthly blood glucose, daily insulin dose (units per kilogram per day), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, apo A-I, and apo B. Choline-containing PL were assessed in plasma and in apo B- and no-apo B-containing lipoprotein particles (LpB and Lp no B). As compared with the control group, plasma PL and LpB-PL were significantly lower in IDDM patients treated by CSII (2.95 +/- 0.26 v 3.30 +/- 0.45 mmol/L,P<.05, and 1.09 +/- 0.45 v 1.68 +/- 0.33 mmol/L,P<.01, respectively). No significant differences were observed for Lp no B lipid determinations between both groups. After initiation of CIPII, IDDM patients did not experience any significant changes in mean values for body mass index, HbA1c, and monthly blood glucose throughout the study. Daily insulin doses were identical to those observed before IP therapy. Lipid parameters remained unchanged in IDDM patients (TC, TG, HDL and LDL cholesterol, apo A-I, and apo B). A moderate but progressive elevation of plasma PL was noted, and after 4 months of CIPII, PL and LpB-PL levels were no longer significantly different between IDDM patients and controls. The increase in plasma and LpB choline-containing PL observed after 2 and 4 months of CIPII is not linked to changes in blood glucose control, body weight or daily insulin requirements. These changes may be related to the route of insulin administration, which may be accompanied by a reduction of lipoprotein lipase (LPL) activity and consequently a reduction of phospholipase activity. These results suggest that IP insulin delivery may be a more physiological route that increases the choline-containing PL content of LpB particles.

Adult↗
PubMed1996

Classification of bacteria nodulating Lathyrus japonicus and Lathyrus pratensis in northern Quebec as strains of Rhizobium leguminosarum biovar viciae.

The diversity of two populations of rhizobia isolated from Lathyrus japonicus (30 strains) and Lathyrus pratensis (49 strains) growing in northern regions of Quebec, Canada, was determined on the basis of phenotypic characteristics, multilocus enzyme electrophoresis, DNA-DNA homology, and 16S ribosomal DNA sequencing. According to numerical analysis of phenotypic characteristics, strains were divided into four groups. Strains isolated from L. pratensis fell in groups I to III; the latter included reference strains of Rhizobium leguminosarum. All strains isolated from L. japonicus were included in group IV. All strains had nodulation characteristics similar to those of R. leguminosarum bv. viciae. Strains isolated from L. japonicus originating from an arctic region were usually able to grow at 5 degrees C and were more likely to be tolerant to copper (CuCl2.H2O, 100 micrograms/ml) and lead [Pb(CH3COO)2, 500 micrograms/ml] than strains isolated from L. pratensis from a boreal zone. However, both populations of Lathyrus strains were adapted to the cold in comparison to reference strains from temperate regions. Each population had similar genetic diversity (H = 0.45), determined by multilocus enzyme electrophoresis of the loci encoding eight enzymes, but the diversity obtained by analyzing all strains including the reference strains (H = 0.58) was higher. Representative strains of both populations showed high levels of DNA homology among themselves and with R. leguminosarum. Partial sequences of the 16S ribosomal RNA genes were similar to those reported for R. leguminosarum bv. viciae. We conclude that the strains isolated from L. japonicus and L. pratensis belong to R. leguminosarum bv. viciae but are distinguishable by growth at 5 degrees C, which is a characteristic related to their geographic origin.

Base Sequence↗
PubMed1996

Hyperinsulinemia is related to erythrocyte phospholipid composition and membrane fluidity changes in obese nondiabetic women.

It has been suggested that changes in the properties of cell membranes are involved in an altered insulin action. However, the influence of changes in the distribution of phospholipid classes has not been explored. We investigated 69 obese nondiabetic normoglycemic women (17 patients with impaired glucose tolerance) with varying degrees of insulin sensitivity to determine the phospholipid composition and fluid state of their erythrocyte plasma membranes. The fasting plasma insulin, the homeostasis model analysis of insulin resistance (HOMA), and the integrated area under the insulin curve (AUC-I) after an oral glucose challenge were used as markers of insulin resistance. Results were divided into normal glucose tolerance (NGT) and impaired glucose tolerance. There was a positive correlation in NGT group between the membrane sphingomyelin (SM) content and the fasting plasma insulin (r = 0.523; P < 0.0001), HOMA value (r = 0.483; P < 0.0005), and AUC-I (r = 0.352; P < 0.05) and negative correlations between membrane fluidity determined with two fluorescent probes and plasma fasting insulin (r = 0.320; r = -0.365; P < 0.05) and HOMA value (r = 0.321; r = -0.382; P < 0.05). There were also correlations between SM and the three markers of insulin resistance in the impaired glucose tolerance group. There was no correlation between insulin resistance and other membrane components. Stepwise multiple regression analysis in the NGT group confirmed that the membrane SM content was an independent predictor of plasma fasting insulin, HOMA values, and AUC-I variations. Sphingomyelin could be one of the membrane parameters contributing to insulin resistance.

Administration, Oral↗
PubMed1996

Accessibility of human apolipoprotein B-100 epitopes in insulin-dependent diabetes: relation with the surface lipid environment of atherogenic particles.

The physicochemical modifications (composition and conformation) of lipoproteins containing apolipoprotein B-100 (apo B-100) were studied in normocholesterolaemic adequately controlled Type 1 insulin-dependent diabetic patients. Thirty-one normocholesterolaemic (serum cholesterol < 6.50 mmol/l) diabetic male patients and 31 age-and body mass index-adjusted healthy normolipaemic male controls were studied. Cholesterol and choline-containing phospholipids were measured in total serum and in two lipoprotein subfractions containing or not apo B (LpB and LpnoB respectively). These subfractions were separated by precipitation with concanavalin A. Total apo B-100 and two lipoprotein particles defined according to their apo B-100 epitope accessibility were determined using respectively anti-apo B polyclonal and two monoclonal antibodies that reacted with specific epitopes on the apo B molecule. Despite a classical lipid profile (cholesterol and triglyceride levels), which was quite normal in plasma from patients as compared to controls, a depletion of choline-containing phospholipid content in serum and more specifically in LpB particles was observed in diabetic patients. Decreased cholesterol content was also observed in LpB particles. Immunological analysis demonstrated an increased number of lipoprotein particles (a condition previously related to coronary artery disease) and decreased immunoaccessibility of a conformationally expressed apo B-100 epitope. These conformational changes were correlated with modifications of the surface phospholipid environment of LpB particles. It is concluded that subtle abnormalities in the composition and conformation of atherogenic apo-B-containing lipoproteins occur in Type 1 diabetes mellitus. These structural modifications may be one factor accounting for the increased rate of atherosclerosis in diabetes, despite the existence of a normal classical lipid profile.

Adult↗
PubMed1995

Laparoscopic staging of early ovarian cancer.

The relevance of staging in early ovarian carcinoma is reviewed in light of the advances in surgical laparoscopy. Data from the literature suggest that a lymphadenectomy should be performed instead of a sampling. We have realized the former through laparoscopy. In this paper we propose a detailed surgical technique, similar to the laparotomy approach, that ensures an adequate nodal evaluation. Ten patients underwent a completion of staging by laparoscopy, including peritoneal washings for cytology, peritoneal and ovarian biopsies, an infracolic omentectomy, and a lymph node dissection. The use of laparoscopy for staging of early ovarian carcinoma appears to be a valuable alternative to traditional surgical staging.

Adult↗
PubMed1995

Decreased erythrocyte membrane fluidity in poorly controlled IDDM. Influence of ketone bodies.

OBJECTIVE: To examine the factors that might alter the fluidity of erythrocyte membrane in insulin-dependent diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS: The subjects were 10 health men and 30 IDDM mem: 10 with good blood glucose (BG) control (HbA1c 5.88 +/- 0.60% [mean +/- SD]), 10 with poor BG control (HbA1C 9.48 +/- 1.05%), and 10 with poor BG control and mild to moderate diabetic ketoacidosis (DKA) (HbA1C 9.12 +/-2.25%, strongly positive ketonuria 3+ and elevated plasma beta-hydroxybutyrate). Erythrocyte membrane fluidity was determined by fluorescence polarization using 6-(9-anthroyloxy stearic acid as fluorescent probe. RESULTS: Membrane fluidity was normal in the diabetic patients with good BG control but significantly lower in the two groups of patients with poor BG control than in the healthy subjects (P < 0.01). The membrane fluidity in the poor BG control groups was also lower in the patients with DKA than in those without DKA (P < 0.01). CONCLUSIONS: The factors that most influence membrane fluidity in IDDM patients appear to be hyperglycemia and ketone bodies.

Adult↗
PubMed1995

[Lipoprotein (a) and diabetes mellitus].

Lp(a) has atherogenic and thrombotic properties and is considered to be a major risk factor for the development of atherosclerotic disease. The risk of cardiovascular disease is increased in both insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), and Lp(a) has attracted attention as a potential risk factor in diabetic patients. Lp(a) levels are "probably" elevated in IDDM patients and related to altered metabolic control and increased urinary albumin excretion rate or renal insufficiency, although results are controversial. There appears to be a real difference between the Lp(a) of patients with proliferative diabetic retinopathy and those with or without background retinopathy. The plasma Lp(a) level may therefore be associated with microangiopathy in some IDDM patients. However, data relating Lp(a) to complications of diabetes are limited, and the literature is conflicting. The few available data suggest that Lp(a) is not elevated in NIDDM patients and that there is no strong link between blood glucose control and plasma Lp(a). There is no clear evidence as to whether Lp(a) is related to microalbuminuria in NIDDM patients. There is little evidence for a correlation between increased risk of cardiovascular disease and plasma Lp(a) among diabetic patients. However, some diabetic patients with coronary heart disease have elevated plasma Lp(a), which seems to be correlated with genetic factors (especially the isoforms of apolipoprotein a) rather than to diabetes per se. Lp(a) synthesis and catabolism could be influenced by insulin or by diabetes and its metabolic concomitants. The atherogenic and thrombogenic potential of Lp(a) could also be increased in diabetic patients. Plasma Lp(a) should be measured for both IDDM and NIDDM patients. If the Lp(a) level is elevated, it seems reasonable to check the other major vascular risk factors.

Cardiovascular Diseases↗
PubMed1995

Non-enzymatic glycosylation of apolipoprotein A-I and its functional consequences.

High-density lipoproteins (HDL) are believed to protect against atherosclerosis by promoting the process of reverse cholesterol transport. This process involves different steps including efflux of cellular cholesterol, cholesterol esterification and lipid transport and exchange. Apolipoprotein (apo) A-I, the major HDL apolipoprotein, and the HDL-associated enzyme lecithin-cholesterol acyltransferase (LCAT), which uses apo A-I as a cofactor, play a crucial role in reverse cholesterol transport. HDL may be classified into species according to their apolipoprotein content. Recent data concerning HDL particles indicate that lipoproteins containing apo A-I but not apo A-II (LpA-I) are more effective carriers of free cholesterol and are associated with a protective effect against coronary heart disease. In vitro studies have shown that glycosylated HDL are functionally abnormal and may be considered atherogenic. Our study considers the different impacts of non-enzymatic glycosylation of apo A-I or protein-HDL on the reverse cholesterol transport process.

Apolipoprotein A-I↗
PubMed1994

Minimal model for determination of insulin sensitivity: repeatability in control and obese subjects.

A mathematical model was recently developed (minimal model) to estimate insulin sensitivity from the analysis of blood glucose and insulin concentration after a modified intravenous glucose tolerance test. This approach was successfully compared with the euglycemic glucose clamp in humans. In this study, we have analysed the distribution and reproducibility of this method in 10 healthy subjects and seven obese patients. We have observed a lower insulin sensitivity (SI) in obese patients (1.96 +/- 0.38 x 10(-4)/min/microU/ml) than in healthy subjects (8.19 +/- 1.16 x 10(-4)/min/microU/ml) with a small overlap between the two groups. The test was repeated twice and good repeatability was found with the method of Blank and Altman when a log transformation was applied to the data.

Adult↗