Search PubMed⌕ Search

Biomedical subjects

S Halimi

Publications and source records attributed to S Halimi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Heat stress fails to protect myocardium of streptozotocin-induced diabetic rats against infarction.

OBJECTIVE: Protection conferred by heat stress (HS) against ischaemia-reperfusion injury, in term of mechanical function and myocardial necrosis, has been extensively studied. In contrast, the effects of disease states on this HS-induced cytoprotective response are less known. Therefore, we investigated the effects of prior heat stress on the infarct size in the isolated heart and on the myocardial heat stress protein (HSP) 72 synthesis, in a model of insulin-dependent diabetic rats. METHODS: Three groups of animals were studied: D rats were rendered diabetic by 55 mg/kg streptozotocin i.v. injection. DI rats received the same treatment plus a daily injection of insulin started 2 weeks after and V rats received the vehicle of streptozotocin plus a daily injection of saline. Eight weeks later, D, DI and V rats were either heat-stressed (42 degrees C for 15 min) or sham-anaesthetised. Twenty-four hours later, their hearts were isolated, perfused using the Langendorff technique, and subjected to a 30 min occlusion of the left coronary artery followed by 120 min of reperfusion. Myocardial HSP72 content was measured 24 h after HS or sham treatment using an electrophoresis coupled with a Western blot analysis. RESULTS: Infarct-to-risk ratio (I/R) was significantly reduced in hearts from heat-stressed (11.7 +/- 2.0%) compared to sham (30.0 +/- 3.2%) V rats. This cardioprotection was not observed in hearts from D (I/R: 31.4 +/- 3.3 vs. 34.3 +/- 3.5%) and DI (I/R: 28.7 +/- 1.6 vs. 30.3 +/- 1.6%) rats. Risk zones were similar between all experimental groups. The incidence of ventricular arrhythmias during ischaemia and reperfusion periods was not different between the six experimental groups. Western blot analysis of the myocardial HSP72 content showed a comparable heat stress-induced increase of this protein, in V, D and DI animals. CONCLUSION: These results demonstrate that myocardial protective effect induced by heat stress could not extend to a pathological animal model like the diabetic rat and seems to be unrelated to the HSP72 level. Further investigations are required to elucidate the precise role of the heat stress proteins in this adaptive response.

Analysis of Variance↗
PubMed1999

End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions.

The incidence of patients with end-stage renal failure and diabetes mellitus type 2 as a comorbid condition has increased progressively in the past decades, first in the United States and Japan, but subsequently in all countries with a western lifestyle. Although there are explanations for this increase, the major factor is presumably diminishing mortality from hypertension and cardiovascular causes, so that patients survive long enough to develop nephropathy and end-stage renal failure. This review summarizes the striking differences between countries against the background of a similar tendency of an increasing incidence in all countries. Survival on renal replacement therapy continues to be substantially worse for patients with type 2 diabetes. A major reason for this observation is that patients enter renal replacement programs with cardiovascular morbidity acquired in the preterminal phase of renal failure. It is argued that the challenge for the future will be better patient management in earlier phases of diabetic nephropathy to attenuate or prevent progression, as well as cardiovascular complications.

Cross-Cultural Comparison↗
PubMed1999

Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. The Diabiopsies Group.

Renal interstitial expansion is now considered a useful marker of progression of several nephropathies. This study describes a multicenter, prospective, double-blind, placebo-controlled, randomized trial of the effects of Perindopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 diabetic patients with proteinuria ranging from 70 to 4210 mg/d and relatively preserved GFR (creatinine clearance >60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the presence of nondiabetic nephropathy. The remaining 22 were randomized ( 11 to Perindopril [PE], 11 to placebo [PO]), and 19 (9 PE, 10 PO) underwent follow-up biopsy at 2 yr. BP was controlled equally in both groups throughout. Proteinuria increased in PO patients (+1562 mg/d) but declined in PE patients (-156 mg/d) (P < 0.05). Morphometric analysis was performed by light microscopy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (31.7 +/- 5.3 versus 40.2 +/- 11.1%; P = 0.001) but was unchanged in PE patients (33.8 +/- 4.9 versus 34.7 +/- 6.6%; P = 0.50). It is concluded that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril prevents interstitial expansion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of interstitial changes in type 2 diabetic patients with nephropathy.

Adult↗
PubMed1999

An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats.

Recently there has been growing interest in the effects of antioxidants on insulin activity. In the present study, we investigated the effect of metformin on free radical activity and insulin sensitivity in high fructose-fed rats, a diet that leads to insulin resistance. The animals were divided into four groups (n = 16 per group; experiment duration = 6 weeks): the control (C) group received a standard diet; the control metformin (CM) group was fed a control diet and received metformin (200 mg x kg(-1) x day(-1) in water); the fructose control (FT) group was fed a diet in which fructose composed 56.8% of the total carbohydrates; and the fructose metformin (FM) group received high-fructose diet and metformin (200 mg x kg(-1) x day(-1) in water). The glucose clamp technique was used to determine insulin sensitivity in eight animals per group. Metabolic and oxidative stress parameters were measured in the remaining rats. In the FT rats, insulin resistance, lower red cell CuZn superoxide dismutase activity and lower blood reduced glutathione were observed. Metformin treatment improved both the insulin activity and the antioxidant defense system. In the CM group, metformin had no effect on metabolic parameters, but improved red cell antioxidant enzyme activities and the blood GSH level, which suggests that it has an antioxidant activity independent of its effect on insulin activity.

Animals↗
PubMed1999

Prediction of cardiovascular events in clinically selected high-risk NIDDM patients. Prognostic value of exercise stress test and thallium-201 single-photon emission computed tomography.

OBJECTIVE: We evaluated the prognostic value of an exercise stress test and thallium-201 scintigraphy for the prediction of cardiac events in selected high-risk NIDDM patients. RESEARCH DESIGN AND METHODS: NIDDM patients (n = 158, 105 men, aged 63 +/- 9 years) with two or more of the following criteria were prospectively included: age > or = 65 years, active smoking, hypertension > 160/95 mmHg, hypercholesterolemia (cholesterol > 5.70 mmol/l or LDL > 3.10 mmol/l), peripheral artery disease, abnormal rest electrocardiogram, or microalbuminuria (20-200 micrograms/min). An exercise-stress scintigraphy was performed in 77 patients able to exercise, while a dipyridamole scintigraphy was performed in 80 patients unable to exercise. Follow-up was 23 +/- 17 months. Major end points were cardiac deaths or nonfatal myocardial infarction. RESULTS: The annual event rate was 7.31% (deaths: 8, myocardial infarction: 14). Independent predictors of events were as follows: an age > 60 (P = 0.02), an abnormal rest electrocardiogram (P = 0.02), microalbuminuria (P = 0.001), the inability to exercise (P = 0.009), and the presence of more than two defects on scintigraphy (P = 0.001). A cardiac death occurred in 1.3% of patients able to exercise versus 8.8% of patients unable to exercise (odds ratio = 6.8, P = 0.001). Among patients unable to exercise, large perfusion defects corresponded to an annual mortality rate of 22.3%. Conversely, the negative predictive value of a normal scintigraphy for the occurrence of death was 97%. CONCLUSIONS: Inability to exercise and large perfusion defects on thallium-201 scan are major predictors of future death and myocardial infarction in high-risk NIDDM patients.

Activities of Daily Living↗
PubMed1999

Huge progression of diabetes prevalence and incidence among dialysed patients in mainland France and overseas French territories. A second national survey six years apart. (UREMIDIAB 2 study).

In 1989, we conducted a survey (UREMIDIAB) on the prevalence of diabetes among the population on Renal Replacement Therapy (RRT) in Mainland France (MF), the lowest of the developed countries (6.9%) with a North-South gradient (higher prevalence in the North). This highlighted a possible (genetical or nutritional) "new french paradox" in mainland France populations. In 1992 we conducted a similar study in the french (mainly non caucasian) overseas territories (OT) hosting 3.2% of the total french population, and observed a prevalence of diabetes in RRT of 22.9%. The frequency of diabetes mellitus as a cause of ESRD increasing worldwide, we conducted a second survey in year 1995, in MF and the OT. This study, UREMIDIAB 2, included all of the 244 french dialysis centers. A "Center file" allowed us to determine the prevalence and incidence of diabetes in the french RRT population, (response rate 73%). Then a "Patient medical file" (response rate 64.8% for MF and 91% for the OT) provided detailed informations: type of diabetes (type 1 or 2), etiology of nephropathy, status of diabetic complications, family's geographic origin of the patient. In MF the prevalence of diabetics in RRT doubled within 6 years: 13.04% vs 6.9%, the incidence reached 15.7%. In the OT the prevalence and the incidence reached 25.7% and 35.6%, respectively. Type 2 diabetes represented 87% and 93% of the RRT diabetics in MF and the OT, respectively. Diabetic nephropathy was considered as the cause of renal failure in 91.3% of type 1 and 57.5% of type 2 diabetics under dialysis. We found: 14.7% of myocardial infarction, 12.7% of cerebral strokes, 17.6% of amputations (extreme 37% in some OT centers) among this diabetic RRT population. A North-East (higher prevalence) South-West (lower) gradient was confirmed. We conclude that, while an unusual low prevalence (< or = 13%) of diabetics under dialysis persists in some parts of Mainland France, the total prevalence has been doubled within 6 years (1989/95) and that in Overseas Territories, hosting similar mixed blood populations than USA (afro-caribbeans, asians, indians, micronesians and metis), the high incidence of diabetes in RRT has reached the US levels during the same period.

Diabetes Mellitus, Type 1↗
PubMed1998

Adenovirus-mediated catalase gene transfer reduces oxidant stress in human, porcine and rat pancreatic islets.

Susceptibility of pancreatic islets to oxidant stress may affect islet viability and contribute to primary non function of allo- or xenogenic grafts. We investigated the influence of overexpression of catalase (CAT) on the viability of human, porcine and rat islets, as well as INS-1 beta-cell line. Islets were transfected with a replication-deficient adenovirus vector containing human CAT cDNA under the control of the adenovirus major late promoter (AdCAT) or a vector containing no foreign gene (AdNull) and used as a control. Oxidant stress was induced 48 h later by xanthine oxidase-hypoxanthine (XO 25 mU/ml, HX 0.5 mmol/l) or hydrogen peroxide (100 or 250 micromol/l). Islet cell viability was assessed 72 h after CAT transfer by 4-[3-(4-Idophenyl)-2-(4 nitrophenyl)-2H-5-tetrazolio]-1,2,benzene disulphonate (WST-1) test. Baseline catalase activity was three to fourfold lower in porcine than in human islets. CAT activity was reproducibly increased 2.5- to 7-fold in AdCAT infected islets, at least for 13 days. Overall, AdCAT conferred on human and pig islets a protection of 26.1 +/- 6.1 and 21.2 +/- 9.8% on XOHX injury and 35.4 +/- 4.2 and 57.9 +/- 10.5% on H2O2 stress. Similarly, rat islet cells and INS-1 cells were protected on XOHX stress by 17.8 +/- 2.3 and 30.8 +/- 8.7%, respectively. AdNull had no effect. Basal and stimulated insulin secretion was preserved in AdCAT-transfected human islets despite a XOHX challenge. This study validates adenovirus-mediated catalase gene transfer as a realistic approach to reduce non specific inflammation effects on human or porcine islet grafts. Moreover the relevance of defense mechanisms, previously suggested in human islets, is here illustrated in porcine islets.

Adenoviridae↗
PubMed1998

ApoE polymorphism and albuminuria in diabetes mellitus: a role for LDL in the development of nephropathy in NIDDM?

BACKGROUND: Chronic hyperglycaemia stands with diabetes duration as the main predicting factor for the development of nephropathy in insulin dependent diabetes mellitus (IDDM). In contrast, nephropathy in non-insulin-dependent diabetes mellitus (NIDDM) presents with a different natural history and, as well as atherosclerosis, can precede diabetes diagnosis and even the onset of patent hyperglycaemia. The role of lipid abnormalities in this matter remains debated. METHODS: We studied the prevalence of nephropathy (N+ = urinary albumin excretion rate (UAE) > 20 mg/d) in 134 Caucasian NIDDM patients ranked according to alipoprotein E (apoE) genotype (same distribution in 132 controls). Age, diabetes duration and sex ratio did not differ between N+ and N-. A patient with E2E4 (n = 1) was excluded from the analysis. RESULTS: The prevalence of nephropathy was significantly reduced in E2 allele carriers (36%, 8/22) vs 69% (77/111) in E2 non-carriers (P < 0.01). Relative risk (RR) of E2 carriers developing nephropathy was 0.52 (95% CI = 0.35-0.80). Both groups were comparable in terms of age (55 +/- 11 vs 57 +/- 11 years), diabetes duration (15 +/- 9 vs 14 +/- 10 years) and prevalence of retinopathy (59 vs 48%). Similar results were observed when patients with diabetes duration longer than 8 years were studied (n = 94). CONCLUSIONS: It has been largely established that low-density lipoprotein (LDL)-cholesterol level in E2 allele carriers (whether diabetic or not) was lower than in E2 non-carriers. The 2-fold increase of nephropathy in E2 non-carriers with NIDDM argues for a role for LDL in the development of human nephropathy in NIDDM patients. This result is in agreement with previous data established both in vitro and in vivo in animal models. These findings support evidence for the pathogenic and morphologic similarities between kidney disease and atherosclerosis in NIDDM patients.

Adult↗
PubMed1998

Strategies for graft immunomodulation in islet transplantation.

Immunomodulation of islets aims at reducing graft immunogenicity and vulnerability to attack by immune competent cells and inflammatory mediators. Data from he International Islet Transplant Registry clearly establish this aspect as a central issue for the future of islet and endocrine cell transplantation. A primary target for graft immunomodulation is donor-derived costimulatory activity. Islet culture at 24 degrees C for 7 days is efficient in decreasing graft immunogenicity without affecting islet viability and can readily be used in clinical transplantation. Low-dose ultraviolet B irradiation may also help improving the effectiveness of immunosuppressive therapy. CTLA4lg appears to be a promising approach to target direct and indirect T-cell activation and may soon be applied to free or encapsulated islet transplants. A second target is the T cell, and strategies rely on a gene transfer approach to switch on T-cell apoptosis using Fas ligand, or to modulate T-cell populations with cytokines. Current results suggest that additional basic investigations are needed. Finally, the beta cell may be manipulated to improve its resistance to inflammatory mediators. Data using transfer of various genes (bcl-2, adenovirus E3, catalase, HSP70) have shown promising perspectives.

Adjuvants, Immunologic↗
PubMed1998

[Benefits of blood glucose self-monitoring in the management of insulin-dependent (IDDM) and non-insulin-dependent diabetes (NIDDM). Analysis of the literature: mixed results].

Since the 1980s, self-monitoring of blood glucose (SMBG) has allowed easier and improved treatment of insulin-dependent diabetes mellitus (IDDM). SMBG has proved efficient in very selected patients and in conditions such as pregnancy, intensive insulin therapy (CSII and optimal bolus regimen), physical exercise and self-awareness of specific hypoglycaemic symptoms. Through the use of pen insulin injectors, SMBG should improve the autonomy, well-being and metabolic control of most IDDM patients. However, as SMBG is continuing to develop in France, costs are rising (estimated at $170 million per year in 1997), which has led some diabetologists to question its real benefit for all diabetic patients and its cost-effectiveness. Our study of published data indicates that SMBG often fails to be beneficial in non-selected IDDM patients, whether children adolescents or adults. However, educational sessions on SMBG and insulin dose adjustment have demonstrated that SMBG improves well-trained patients. Most authors recommend applying psychosocial scales and suitable educational tools to obtain positive results and justify the human and economic costs involved. In non-insulin-dependent diabetes mellitus (NIDDM), the use of SMBG is increasingly recommended by diabetologists and general practitioners. However, trials investigating the effects of SMBG in NIDDM patients have found no benefit for metabolic control or weight loss. We recommend a moderate use of SMBG in NIDDM patients and the development of clinical research strategies to study the benefit for NIDDM patients of a method which is increasing health costs appreciably.

Blood Glucose Self-Monitoring↗
PubMed1997

Standardization of procedure for efficient ex vivo gene transfer into porcine pancreatic islets with cationic liposomes.

BACKGROUND: New strategies to improve the outcome of encapsulated porcine islet transplantation may involve the transfer of gene sequences affecting islet viability. While adenoviral vectors appear as the most efficient gene transfer system so far established for islets, non-viral-based vectors are most likely to fulfill microbiological safety criteria and be retained in the clinical setting. Our aim was to standardize the procedures of gene transfer into adult porcine islets using cationic liposome DOTAP. METHODS: Porcine islets obtained by collagenase digestion and density gradient purification were lipofected with plasmids coding for luciferase or beta-galactosidase under the control of simian virus 40 or cytomegalovirus promoter. The following parameters were explored: exposure time to vector (1-48 hr), DNA amount (1-15 microg/500 islets), and DOTAP to DNA ratio (2-16). Reporter gene expression was determined 48-72 hr after lipofection. RESULTS: Efficiency and reproducibility of transfection were maximal with the following procedure: 3-hr exposure time followed by islet washing, 12 microg of DNA per 500 islets (150 microm equivalent), and DOTAP to DNA ratio of 12 microl/microg. Freshly isolated islets in large aliquots (n=4000 in 50-ml tubes) were efficiently transduced with this procedure, and distribution of gene expression was homogenous when islets were subsequently plated in 500-islet aliquots. Luciferase gene expression was detected for a minimum of 7 days after lipofection. Gene expression was also evident up to 4 weeks after islet transplantation beneath the kidney capsule of athymic mice. Transfection of islets using the beta-galactosidase vector yielded 25% positive islets. Islet viability was not adversely affected. CONCLUSIONS: This islet lipofection procedure may help achieve the local release of a bioactive peptide in the graft environment and have therapeutic applications in islet transplantation.

Animals↗
PubMed1997

Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group.

Diabetic nephropathy is a glomerular disease due to uncontrolled diabetes and genetic factors. It can be caused by glomerular hypertension produced by capillary vasodilation, due to diabetes, against constitutional glomerular resistance. As angiotensin II increases glomerular pressure, we studied the relationship between genetic polymorphisms in the renin-angiotensin system-angiotensin I converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II, subtype 1, receptor-and the renal involvement of insulin-dependent diabetic subjects with proliferative retinopathy: those exposed to the risk of nephropathy due to diabetes. Of 494 subjects recruited in 17 centers in France and Belgium (GENEDIAB Study), 157 (32%) had no nephropathy, 104 (21%) incipient (microalbuminuria), 126 (25 %) established (proteinuria), and 107 (22%) advanced (plasma creatinine > or = 150 micromol/liter or renal replacement therapy) nephropathy. The severity of renal involvement was associated with ACE insertion/deletion (I/D) polymorphism: chi2 for trend 5.135, P = 0.023; adjusted odds ratio attributable to the D allele 1.889 (95% CI 1.209-2.952, P = 0.0052). Renal involvement was not directly linked to other polymorphisms. However, ACE I-D and AGT M235T polymorphisms interacted significantly (P = 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes. Thus, genetic determinants that affect renal angiotensin II and kinin productions are risk factors for the progression of glomerular disease in uncontrolled insulin-dependent diabetic patients.

Adult↗
PubMed1997

Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose diets.

The purpose of this study was to investigate the effects of vitamin E in rats fed a high fructose diet which leads to insulin resistance, on some components of the free radical defense system and on insulin sensitivity. The rats (postweaning, 50 g) were divided into three groups: the control group (C, n = 16), which received a purified diet containing 60 g/100 g carbohydrates, the high fructose-fed group (FT, n = 16),fed a diet in which 56.8% of the carbohydrate as fructose, and a high fructose and vitamin E-fed group (FVE, n = 16), fed the FT diet supplemented with 3.4 g vitamin E/kg diet (vs. 0.17 g/kg in C and FT groups). The duration of the treatment was 6 wk. Insulin sensitivity was determined in half of the rats in each group using the euglycemic hyperinsulinic glucose clamp technique. The remaining rats were investigated for plasma glucose, insulin, triglyceride and fructosamine concentrations and for components of the free radical defense system. The FT group had a significantly lower insulin sensitivity than the C group. Basal glycemia was not different among the groups. In comparison with the C group, the FT group had a greater lipid peroxidation, as indicated by the higher concentrations of plasma thiobarbituric acid reactive substances (TBARS) and blood disulfide glutathione (GSSG) and the lower Cu-Zn superoxide dismutase (Cu-Zn SOD) activity. These markers approached the values of the controls after addition of vitamin E. Moreover, the FVE group had a higher insulin sensitivity than the FT group, but it remained lower than in the C group. These results show that a high fructose diet in rats leads to insulin resistance and a defect in the free radical defense system. Vitamin E supplementation improves insulin sensitivity in fructose-fed rats.

Animals↗