PubMed Health⌕ Search

Biomedical subjects

P Duriez

Publications and source records attributed to P Duriez.

At least 19 recordsLinked to original sources
PubMed2006

PPAR: a new pharmacological target for neuroprotection in stroke and neurodegenerative diseases.

PPARs (peroxisome-proliferator-activated receptors) are ligand-activated transcriptional factor receptors belonging to the so-called nuclear receptor family. The three isoforms of PPAR (alpha, beta/delta and gamma) are involved in regulation of lipid or glucose metabolism. Beyond metabolic effects, PPARalpha and PPARgamma activation also induces anti-inflammatory and antioxidant effects in different organs. These pleiotropic effects explain why PPARalpha or PPARgamma activation has been tested as a neuroprotective agent in cerebral ischaemia. Fibrates and other non-fibrate PPARalpha activators as well as thiazolidinediones and other non-thiazolidinedione PPARgamma agonists have been demonstrated to induce both preventive and acute neuroprotection. This neuroprotective effect involves both cerebral and vascular mechanisms. PPAR activation induces a decrease in neuronal death by prevention of oxidative or inflammatory mechanisms implicated in cerebral injury. PPARalpha activation induces also a vascular protection as demonstrated by prevention of post-ischaemic endothelial dysfunction. These vascular effects result from a decrease in oxidative stress and prevention of adhesion proteins, such as vascular cell adhesion molecule 1 or intercellular cell-adhesion molecule 1. Moreover, PPAR activation might be able to induce neurorepair and endothelium regeneration. Beyond neuroprotection in cerebral ischaemia, PPARs are also pertinent pharmacological targets to induce neuroprotection in chronic neurodegenerative diseases.

Brain↗
PubMed2004

[Anti-cholesterol agents, new therapeutic approaches].

Statins and fibrates constitute the two major families of lipid-lowering agents. Statins are widely used for the treatment of pure hypercholesterolaemia while fibrates are used for the treatment of hypertriglyceridemia. Both drugs are also used for the treatment of mixed dyslipidemia. Some fibrates efficiently lower serum LDL-cholesterol. Statins inhibit HMG-CoA reductase and decrease cellular cholesterol synthesis. The resulting lower intracellular cholesterol concentration induces the activation of SREBP thus inducing the over expression and transcription of the LDL receptor gene. This over expression of the LDL receptor in the liver increases the clearance of circulating LDL thus decreasing the LDL-cholesterol plasma levels. The effects of fibrates on lipid metabolism are entirely due to their capacity to activate PPAR-alpha and to induce the over expression of genes containing a PPRE in their promoter. Fibrates decrease triglyceride concentrations by increasing the beta-oxidation of fatty acids in the liver and by decreasing triglyceride-VLDL synthesis. Fibrates also decrease triglycerides by increasing the hydolysys of triglycerides in chylomicron and VLDL through their capacity to increase and to decrease the lipoprotein lipase and the apo C-III transcription, respectively. Fibrates could decrease triglycerides partly by inducing apo A-V over-expression. These molecules increase HDL-cholesterol by increasing apo A-I and apo A-II transcription. Therefore the mechanisms of action of statins and fibrates depend on their capacity to modulate the expression of genes controlling lipoprotein metabolism.

Animals↗
PubMed2003

Fatty acid abnormalities in chronic pancreatitis: effect of concomitant diabetes mellitus.

OBJECTIVE: Patients with chronic pancreatitis suffer from malabsorption and nutritional deficiencies. However there is little data available concerning the fatty acid profile in chronic pancreatitis. Diabetes mellitus, a common complication of this disease, could interfere with the metabolism of fatty acids. SUBJECTS: We therefore compared the fatty acid composition of LDL from four groups of male patients with (a) chronic pancreatitis without diabetes (ND-CP; n=12), (b) diabetes secondary to chronic pancreatitis and insulin-treated (CP-D; n=35); (c) type 1 diabetes (n=25); and (d) controls (n=20). RESULTS: The patients in both groups of chronic pancreatitis (ND-CP and CP-D) had lower mean values for linoleic acid than that seen in the type 1 DM and control groups, whereas monounsaturated fatty acids (MUFA; 18 : 1(n-9) and (16 : 1(n-7)) were significantly increased in these two groups (ND-CP and CP-D). Docosa-hexaenoic-acid (22 : 6(n-3)) was significantly decreased in the CP-D group (P>0.05), a response that could be explained by the effects of diabetes mellitus and by selenium deficiency. In this way, diabetes was associated with a decrease in the docosa-hexaenoic-acid (22 : 6(n-3); r=0.30, P=0.005), and selenium was correlated with DHA (r=0.28, P=0.029) and with the 22 : 6(n-3)/20 : 5(n-3) ratio (evaluating the delta 4 desaturation); r=0.31, P=0.022), independently of the diabetes effect. Selenium was negatively correlated with 20 : 4(n-6)/20 : 3(n-6) ratio (evaluating the delta 5 desaturase; r=-0.30; P=0.025). These results suggest that these two factors may have a role in the regulation of the desaturation process. If we consider that a ratio of 16 : 1(n-7)/18 : 2(n-6) greater than 0.086 in plasma indicates an EFAn-6 deficiency, 40% of our CP patients, 57.6% of CP-D patients and 13.6% of type 1 DM patients were involved. CONCLUSIONS: The consequences of these deficiencies are not evaluated in this disease. However, correction of the fundamental deficiencies in essential fatty acids and in selenium seems desirable in chronic pancreatitis.

Adult↗
PubMed2003

[Coronary angioplasty using 5 or 6 F guide catheters. Results of a comparative, monocentric, prospective randomized study].

Improvement of balloon and stent profile allows to use smaller-diameter catheters to avoid vascular complications by reduce the size of puncture site. First studies using 5 F guiding catheters showed good results in term of safety and feasibility. The authors performed a prospective, randomised study to define exactly the place of such small catheter compared to 6 F approach. One hundred forty eight patients were randomised, 77 in the 5 F group. The success rate per lesions was not significantly different but was less in the 5 F group (91.1 vs 96.5%). The crossover to 6 F allows good results in mainly cases. Limitations are unstable back up, worse opacification, and inability to use covered stent and to treat bifurcation lesions. There are no advantages in term of vascular complications. So, these catheters seem to be limited to treat simple lesion, allowing using the same sheath immediately after coronarography, but these results must be confirmed in a large, multicentric study.

Adult↗
PubMed2003

Hawthorn extracts inhibit LDL oxidation.

Polyphenol-rich diet decreases cardiovascular risk. LDL oxidation is the primary event in atherosclerosis plaque formation and antioxidants such as polyphenols were shown to inhibit LDL oxidation and atherosclerosis development. Hawthorn (Crataegus) and derived pharmaceuticals are rich in polyphenols and already prescribed to treat moderate heart failure, nervousness and sleep disorders. Extracts either from fresh plant parts (flower buds, flowers, young leaves or green fruits) or from dried pharmaceutical parts (flowers and flowering tops) were previously shown to be effective inhibitors of lipoperoxidation and scavengers of oxygen species. In this study, the capacity of total and ethyl-acetate extracts from dried pharmaceutical flowers, tops and fruits to inhibit Cu(2+)-induced LDL oxidation was tested. This capacity was positively linked to their content in total polyphenols, proanthocyanidins (global and oligomeric forms), as well as to their content in two individual phenolics: a flavanol, the dimeric procyanidin B2 and a flavonol glycoside, hyperoside. Flavanol-type phenolics showed to be higher active than the majority of the flavonoids tested in inhibiting Cu(2+)-induced LDL peroxidation. This study suggests that hawthorn could be a source of polyphenols able to inhibit LDL oxidation.

Acetates↗
PubMed2002

Peroxisome proliferator-activated receptor activators inhibit oxidized low-density lipoprotein-induced endothelin-1 secretion in endothelial cells.

Endothelin is a potent vasoconstrictor peptide isolated from endothelial cells and it induces smooth muscle cell proliferation. Endothelin-1 secretion is increased in atheroma and induces deleterious effects such as vasospasm and atherosclerosis. Oxidized low-density lipoproteins (LDLs) induce atherosclerosis in the vascular wall, as well as endothelin-1 secretion in endothelial cells and are activators of both peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-gamma. PPAR-alpha (fibric acids) and PPAR-gamma (glitazones) activators are used to treat dyslipoproteinemias and type 2 diabetes, respectively. Furthermore, these drugs induce numerous pleiotropic effects, such as inhibiting thrombin-induced endothelin-1 secretion in endothelial cells. This study shows that both PPAR-alpha (Wy 14643) and PPAR-gamma activation (rosiglitazone) partially inhibit oxidized LDL-induced protein kinase C activity and endothelin-1 secretion in endothelial cells at the transcriptional levels and suggests that synthetic PPAR activators are stronger PPAR activators than oxidized LDL. This study also suggests that fibrate and glitazone treatments should have beneficial effects on the vascular wall by reducing endothelin-1 secretion and the resulting vasospasm and atherosclerosis.

Animals↗
PubMed2001

PPARalpha agonists inhibit tissue factor expression in human monocytes and macrophages.

BACKGROUND: Monocytic tissue factor (TF) expression may contribute to thrombogenicity associated with plaque rupture and may propagate thrombus formation at the site of vascular lesions. Induction of monocytic TF expression by endotoxin is mediated by the activation of transcription factors such as AP-1 and NF-kappaB. Both these signaling pathways are modulated by peroxisome proliferator-activated receptor-alpha (PPARalpha). Therefore, we have studied the effects of fibrates and other PPARalpha agonists on the expression of TF. METHODS AND RESULTS: We show that PPARalpha protein, like primary human monocytes, is also expressed in the human monocytic THP-1 cell line. Fenofibric acid, WY14643, and GW2331 inhibited TF mRNA upregulation after stimulation of THP-1 cells with lipopolysaccharide or interleukin-1ss. In primary human monocytes and macrophages, the lipopolysaccharide- or interleukin-1ss-mediated induction of TF activity was also inhibited by fenofibric acid, WY14643, or GW2331. CONCLUSIONS: These data indicate that activation of PPARalpha results in the downregulation of the TF gene. Our results suggest a novel role for PPARalpha in the control of atherosclerotic plaque thrombogenicity through its effects on TF expression in monocytes and macrophages.

Butyrates↗
PubMed2001

Di-tert-butylhydroxylated flavonoids protect endothelial cells against oxidized LDL-induced cytotoxicity.

The protective effect of di-tert-butylhydroxylated flavonoids (chalcones and arylidenes) against minimally oxidized LDL (mO-LDL)-induced cytotoxicity was studied in cultured bovine aortic endothelial cells. Most of the tested compounds decreased aldehydes formation in medium containing mO-LDL, but their capacity to inhibit LDL oxidation in the cellular medium was not sufficient to totally reduce the cellular toxicity of mO-LDL. Most of the tested flavonoids improved the integrity of cells exposed to mO-LDL, whereas butylated hydroxytoluene was ineffective and quercetin worsened the toxicity of mO-LDL. Moreover these flavonoids induced an increase in GSH cellular levels and their protective effects might be because of their inability to reduce metal ion. Arylidene 6 substituted at position 7 by a hydroxyl group was the most potent compound.

Adenosine Triphosphate↗
PubMed2001

PPARS, metabolic disease and atherosclerosis.

PPAR-alpha belongs to the family of nuclear receptors. Activated PPAR-alpha stimulates the expression of genes involved in fatty acid and lipoprotein metabolism. PPAR-alpha activators, such as the normolipidaemic fibric acids, decrease triglyceride concentrations by increasing the expression of lipoprotein lipase and decreasing apo C-III concentration. Furthermore, they increase HDL-cholesterol by increasing the expression of apo A-I and apo A-II. PPAR-alpha activation by fibric acids improves insulin sensibility, and decreases thrombosis and vascular inflammation. PPAR-alpha activators (gemfibrozil) decrease the risk of coronary heart disease in patients with normal LDL-cholesterol and low HDL-cholesterol (VA-HIT) and they slow the progression of premature coronary atherosclerosis (BECAIT) (bezafibrate), particularly in patients with type 2 diabetes (DAIS) (fenofibrate).

Animals↗
PubMed2001

The role of fibric acids in atherosclerosis.

The hypolipidemic fibric acid drugs are peroxisome proliferator-activated receptor a (PPAR alpha) ligands. PPAR alpha activated by fibric acids form heterodimers with the 9-cis retinoic acid receptor (RXR). The PPAR/RXR heterodimers bind to peroxisome proliferator response elements (PPRE), which are located in numerous gene promoters and increase the level of the expression of mRNAs encoded by PPAR alpha target genes. Fibric acids decrease triglyceride plasma levels through increases in the expression of genes involved in fatty acid-beta oxidation. Furthermore, they decrease triglycerides by increasing lipoprotein lipase gene expression and by decreasing apolipoprotein C-III gene expression. Fibric acids increase high-density lipoprotein (HDL) cholesterol partly by increasing apolipoprotein A-I and apolipoprotein A-II gene expression. Fibric acids also reduce vascular wall inflammation and the expression of genes involved in different vascular functions (ie, vasomotricity, thrombosis). Fibric acids are used to treat primary hypertriglyceridemia and mixed hyperlipidemia. Some fibric acid molecules are active in essential hypercholesterolemia. Clinical evidence shows that fibric acids reduce coronary atherosclerosis progression in dyslipidemic patients (eg, bezafibrate, gemfibrozil) and in type 2 diabetic patients (fenofibrate). Gemfibrozil decreases coronary morbidity and mortality in patients with low HDL cholesterol, normal triglycerides,and normal low-density lipoprotein (LDL) cholesterol plasma levels. Further clinical studies are necessary to investigate if fibric acids decrease cardiovascular mortality in type 2 diabetes and in primary prevention of hypertriglyceridemia and hypolipidemia.

Arteriosclerosis↗
PubMed2001

Effect of the inflammation, chronic hyperglycemia, or malabsorption on the apolipoprotein A-IV concentration in type 1 diabetes mellitus and in diabetes secondary to chronic pancreatitis.

The metabolism of apolipoprotein (apo) A-IV in diabetes mellitus (DM) is poorly understood. Several factors, such as dietary fat intake, fat malabsorption, acute inflammation, and hormonal dysregulation can disturb the plasma apo A-IV concentration. We have compared the plasma apo A-IV concentrations in patients with type 1 DM and DM secondary to chronic pancreatitis to determine the effects of combinations of these factors. We examined 4 groups of male patients with chronic pancreatitis without diabetes (ND-CP) (n = 12), diabetes secondary to chronic pancreatitis and insulin-treated (CP-DM) (n = 32), type 1 diabetes (n = 25), and controls (n = 20). Plasma apo A-IV was significantly lower in the chronic pancreatitis patients (ND-CP and CP-DM) than in the other patients. Inflammatory proteins (fibrinogen, ceruloplasmin, and haptoglobin) were significantly elevated in the 2 chronic pancreatitis groups. The apo A-IV concentration was positively correlated with hemoglobin A(1c) (HbA(1c)) percentage in each group of diabetic patients (CP-DM, r =.35; P =.046; type 1 DM, r =.53; P =.010), in both groups of diabetic patients (r =.472; P <.0001) and negatively correlated with ceruloplasmin concentration in each group of diabetic patients (CP-DM, r = -.48; P =.0052; type 1 DM, r = -.66; P =.003), in both groups of diabetic patients (r = -.561; P <.0001), and in the whole population (r = -.463; P <.0001). Apo A-IV was also negatively correlated with haptoglobin in type 1 DM patients (r = -.434; P =.0435), in the both groups of diabetic patients (r = -.349; P =.0154), and in the whole population (r = -.351; P =.0019). Multiple linear regression analysis revealed that only HbA(1c) and ceruloplasmin were independent explanatory variables. Plasma apo A-IV is positively correlated with HbA(1c) suggesting that hyperglycemia per se selectively affects apo A-IV metabolism. The correlation between the concentrations of inflammatory protein and apo A-IV suggest a link between chronic inflammation and apo A-IV synthesis or catabolism. As apo A-IV is involved in reverse cholesterol transport, its low level in CP-DM may contribute to the accelerated development of atherosclerosis in these patients.

Adult↗
PubMed2001

Mutator natural Escherichia coli isolates have an unusual virulence phenotype.

A small percentage of natural Escherichia coli isolates (both commensal and pathogenic) have a mutator phenotype related to defects in methyl-directed mismatch repair (MR) genes. We investigated whether there was a direct link between the mutator phenotype and virulence by (i) studying the relationships between mutation rate and virulence in a mouse model of extraintestinal virulence for 88 commensal and extraintestinal pathogenic E. coli isolates and (ii) comparing the virulence in mice of MR-deficient and MR-proficient strains that were otherwise isogenic. The results provide no support for the hypothesis that the mutator phenotype has a direct role in virulence or is associated with increased virulence. Most of the natural mutator strains studied displayed an unusual virulence phenotype with (i) a lack of correspondence between the number of virulence determinants and pathogenicity in mice and (ii) an intermediate level of virulence. On a large evolutionary scale, the mutator phenotype may help parasites to achieve an intermediate rate of virulence which mathematical models predict to be selected for during long-term parasite-host interactions.

Animals↗
PubMed2001

Evolution pattern of auto-antibodies against oxidized low-density lipoproteins in renal transplant recipients.

An increased degree of oxidative stress in renal transplant recipients and a possible role of ciclosporin A (Cs-A) immunosuppressive therapy in this process have already been described. However, prospective data using in vivo markers and the influence of Cs-A in the oxidizability of low-density lipoprotein (LDL) are scarce. We aimed at investigating in this prospective study the evolution pattern of auto-antibodies directed against malondialdehyde-modified LDL (MDA-LDL) and Cu2+-oxidized LDL in 28 stable renal transplant recipients on Cs-A immunosuppressive therapy before and after 3 successive years of renal transplantation. Also, the effect of enrichment of LDL with Cs-A on the susceptibility of LDL to in vitro oxidation was tested. The results showed a significant increase of both auto-antibody titres (MDA-LDL and Cu2+-oxidized LDL) after 1 year, and the values remained high during the 2nd and the 3rd year following transplantation. The yearly mean relative variations of auto-antibodies against MDA-LDL and Cu2+-oxidized LDL during the follow-up period were 133, 149, and 137%, and 111, 115, and 117%, respectively. A significant correlation was observed during the 1st year between Cs-A trough blood level and Cu2+-oxidized LDL auto-antibody: r = 0.04 (p = 0.046). Incorporation of Cs-A into LDL from healthy volunteers showed no changes during the lag phase in comparison with Cs-A-free LDL, indicating that Cs-A had no effect on in vitro LDL oxidizability. Our results suggest that Cs-A may be involved earlier in the LDL oxidation, but the mechanism by which it acts is still unclear.

Autoantibodies↗
PubMed2001

Current practice in the treatment of hyperlipidaemias.

Primary and secondary prevention trials for coronary heart disease (CHD) in hyperlipidaemic or so-called 'normolipidaemic' patients with drugs affecting lipid metabolism have clearly confirmed that even slight alterations in lipoprotein metabolism are major risk factors for CHD. The global cardiovascular risk must be determined before deciding to treat patients with drugs affecting lipid metabolism. Screening for dyslipidaemia consists of determining cholesterol (C), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and triglyceride (TG) plasma levels and the decision to treat depends mainly on LDL-C plasma levels. Furthermore, secondary dyslipidaemia must be diagnosed and primary disease must be adequately treated. There are four classes of available lipid-regulating drugs: HMG-CoA reductase inhibitors (statins), bile acid sequestrants (resins), peroxisome proliferator-activated receptor-alpha (PPAR- alpha) activators (fibrates) and nicotinic acid. All four will be discussed in this review. Clinical trials have shown that drugs improving lipid metabolism reduce CHD relative risk from 24% (secondary prevention) to 37% (primary prevention) and the absolute risk from 2% (primary prevention) to 8.5% (secondary prevention). These studies indicate that the number of patients needed to be treated to economise one clinical event ranges from 12 (secondary prevention) to 50 (primary prevention). Clinical trials are currently testing the hypothesis that 'lower LDL-C is better'.

Animals↗
PubMed2001

Increased levels of high-density lipoprotein cholesterol are ineffective in inhibiting the development of immune responses to oxidized low-density lipoprotein and atherosclerosis in transgenic rabbits expressing human apolipoprotein (apo) A-I with severe hypercholesterolaemia.

High levels of high-density lipoprotein (HDL) cholesterol have been reported to protect against the development of atherosclerosis in humans by increasing reverse cholesterol transport and inhibiting the oxidation of low-density lipoprotein (LDL) due to the paraoxonase content of HDL. The purpose of the present study was to assess if there are any relationships between in vivo increases in serum levels of immunological LDL oxidation markers [autoantibodies against oxidized LDL, autoantibodies against malondialdehyde-modified LDL, LDL immune complexes and anti-cardiolipin autoantibodies], paraoxonase activity and the development of atherosclerosis in control rabbits and in transgenic rabbits expressing human apolipoprotein (apo) A-I. A total of 13 apo A-I transgenic rabbits and 18 non-transgenic littermates were fed on a cholesterol-rich diet (0.4%, w/w) for 14 weeks, and were monitored at weeks 0, 2, 6, 10 and 14. Aortic atherosclerotic lesions were measured at the end of this period. Human apo A-I transgenic rabbits with high HDL cholesterol levels were not protected against the development of atherosclerosis when they were fed on a cholesterol-rich diet which induced dramatic hypercholesterolaemia. Immunological markers of LDL oxidation increased and serum paraoxonase activity decreased similarly in control and transgenic rabbits. In conclusion, the present study demonstrates that high HDL cholesterol levels are ineffective in inhibiting increases in immunological markers of LDL oxidation and the development of atherosclerosis in a mammal with severe hypercholesterolaemia.

Animals↗
PubMed2001

[Fundamental data on atherosclerosis].

Atherosclerosis, a disease of large arteries is the primary cause of heart disease and stroke and is the cause of 50% of all deaths in industrialized countries. Epidemiological studies have revealed several important environmental (smoking, sedentary life, feeding) and genetic risk factors associated with atherosclerosis. Knowledge on molecular and cellular causes of atherosclerosis have considerably progressed for 20 years. However, it is highly difficult to propose a valuable atherogenesis model because numerous molecular and cellular abnormalities interact together to induce atheroma. Nevertheless, over the past decade, transgenic animals gave interesting physiopathological models of atherogenesis and the opportunity to elaborate a pertinent theory of plaque formation. It is now demonstrated that atherosclerosis is not a simple chronic degenerescence of vascular wall, depending on age and other risk factors (dyslipidaemia, smoking, diabetes) but rather a chronic inflammatory disease, which induces plaque rupture and acute cardiovascular disease (myocardial infarction and stroke).

Animals↗