A review on microbial contamination cases in Tunisian coastal marine areas.

Microbial pollution in marine environments is one of the critical issues with regard to the sanitary status of recreational activities and seafood harvesting due to a potential contamination by pathogenic microorganisms. This review's objectives were to identify instances of bacterial, viral and protozoan parasite pollution in the Tunisian coastal region and to make recommendations for further research. Fecal indicators such as Escherichia coli and Salmonella spp. were detected in samples of clams and mussels. Vibrionaceae species were also recorded in seawater, sediment, fish and clams in different sites from north to south with the dominance of Vibrio alginolyticus. Bivalve mollusks collected from the Tunisian coast have been revealed to harbor viruses as well as protozoan parasites. Furthermore, the isolation of multidrug-resistant bacterial strains from Tunisian coastlines proves the significant spread and circulation of antibiotic resistance caused by the massive use of antibiotics. In conclusion, we suggest intensive monitoring and cutting-edge wastewater treatment technologies to enhance seawater quality and preserve the biodiversity of aquatic life. Rapid detection techniques for the most important pathogenic microorganisms in seafood and seawater must be also developed to reduce human health risk.

Chemical Composition Analysis, Antioxidant, and Antibacterial Activities of Eggplant Leaves.

Agricultural by-products represent one of the biggest pollutants for the environment, therefore, investigating new sources for the extraction of bioactive compounds is a topic of great interest for the entire scientific community. This work is aimed at studying the chemical composition (pigments, phenolics, volatile compounds) and biological activities (antioxidant and antimicrobial properties) of young and mature leaves of five eggplant cultivars (Solanum melongena L.) grown in Tunisia (Tizona, A1014, Nawel, A336, and Mirval). Pigment analysis showed no statistical variations between the two types of leaves, whereas higher levels of anthocyanins were recorded in young leaves of three out of five cultivars (24.7-52.8 mg 100 g-1 ). Total phenolic compounds (966.5-2072.6 mg 100 g-1 ) and o-diphenols (343.9-741.2 mg 100 g-1 ) contents varied significantly according to leaf age and cultivar. However, no statistically significant variation between young and mature leaves was found in flavonols and tannins content. As for volatile profiles, 62 constituents were characterized with non-terpene derivatives (52.0-61.6 %) and apocarotenes (19.9-35.6 %) as major chemical classes. Regarding the antioxidant activity, methanol extracts of Tizona cultivar mature leaves displayed important antiradical properties using DPPH, ABTS, and phosphomolybdenum assays (IC50 0.1, 0.2 and 0.01 mg mL-1 , respectively). With regards to reducing power determination, the most active extract was obtained from mature A1014 leaves. Further, young Mirval leaves proved to be significantly active from a bactericidal point of view against Candida albicans and Staphylococcus aureus of 3.1 mg mL-1 and 0.2 mg mL-1 MBC, respectively. In conclusion, eggplant leaves are a noteworthy source of antioxidant and antimicrobial compounds with potential use in the pharmaceutical, the cosmetics and the food industries.

Investigation of caffeine taste mechanism through a statistical physics modeling of caffeine dose-taste response curve by a biological putative caffeine adsorption process in electrophysiological response.

This work is a contribution to understand the taste mechanism of caffeine molecule using a modeling of a putative adsorption process by model expressions established by a statistical physics treatment. A physicochemical and a gustative parts are the main constituents of this work. We start with a physicochemical investigation of the adsorption process of caffeine molecule, as adsorbate in liquid phase, onto ß-cyclodextrin as adsorbent. Experimental adsorption isotherm curves of caffeine onto ß-cyclodextrin coated onto Quartz crystal are carried out at three different temperatures. The Hill model expression with three parameters n, NM and C1/2, established by statistical physics formalism investigated in part I, is the best fitting model of the experimental data. Thermodynamic potential functions that govern the adsorption process, such as entropy, internal energy and Gibbs free enthalpy are investigated. PSD and AED are derived by a steric and energetic derivatives of the Hill model. In part II the same method of fitting is applied to the taste electrophysiological dose-response curve by a caffeine putative adsorption on gustative nerve in caterpillar. All the physicochemical parameters introduced in the fitting Hill model expression, serve first, to analyze the taste mechanism of the bitter caffeine taste. Secondly, all these stereographic and energetic parameters will be considered henceforward for an objective characterization of caffeine molecule taste in both its two aspects, intensive and qualitative aspects of caffeine taste.

Characterization of fig achenes' oil of Ficus carica grown in Tunisia.

This work investigated the composition of the oil extract from achenes of "Kholi" variety of Ficus carica, grown in Tunisia. Fatty acid and sterol compositions were analyzed by gas chromatography (GC) coupled to flame ionization detector (FID). Furthermore, the antioxidant capacity in fig achenes' oil was assessed by employing two different in vitro assays such as DPPH, ABTS(+) radical scavenging capacities. Our results indicated that the fig achenes' oil is a rich source of bioactive molecules. The soxhlet n-hexane extraction of these achenes produced a total oil yield of 16.24%. The predominant fatty acid was linolenic acid. Concerning phytosterols, the total amount reached 1061.45 mg/100 g with a predominance of Δ(5,23)-stigmastadienol (73.78%). Regarding antioxidant activities, the half maximal inhibitory concentration (IC50) was 215.86 µg/ml and Trolox equivalent antioxidant capacity (TEAC) was 95.25 mM. These data indicate that fig achenes oil of F. carica could be potentially useful in food and pharmaceutical applications.

The Effect of Vitis vinifera L. Leaves Extract on Leishmania infantum.

Vitis vinifera L.is a traditional Asian herb widely used for different health problems. In the present research, the ethanolic and the aqueous extracts of Vitis vinifera L. leaves collected from shrub, grown in Tunisia, were prepared and evaluated for the antileishmanial activity against Leishmani ainfantum promastigotes. The inhibitory concentration 50 (IC50) was determined and the results showed that the etahnolic extract is more active than the aqueous one (IC50= 0.108 mg/mL). Microscopic observations showed that the ethanolic extract promoted the destruction of cytoplasmic and nuclear membranes of Leishmani ainfantum promastigotes and altered the overall shape of the cell. In order to explain the difference of antileishmanial activity between ethanolic and aqueous extracts, anthocyanins amount was determined by spectrophotometry. It was found that the ethanolic extract is richer in anthocyanins than the aqueous one which can explain the higher antileishmanial activity of the ethanolic extract.

Alteration of lipid status and lipid metabolism, induction of oxidative stress and lipid peroxidation by 2,4-dichlorophenoxyacetic herbicide in rat liver.

This study aims to investigate the effects of the 2,4-dichlorophenoxyacetic herbicide (2,4-D) on plasma lipids, lipoproteins concentrations, hepatic lipid peroxidation, fatty acid composition and antioxidant enzyme activities in rats. Animals were randomly divided into four groups of 10 each: control group and three 2,4-D-treated groups G1, G2 and G3 were administered 15, 75 and 150 mg/kg/BW/d 2,4-D by gavage for 28 d, respectively. Results showed that 2,4-D caused significant negative changes in the biochemical parameters investigated. The malondialdehyde level was significantly increased in 2,4-D-treated groups. Fatty acid composition of the liver was also significantly changed with 2,4-D exposure. Furthermore, the hepatic antioxidant enzyme activities were significantly affected. Finally, 2,4-D at the studied doses modifies lipidic status, disrupt lipid metabolism and induce hepatic oxidative stress. In conclusion, at higher doses, 2,4-D may play an important role in the development of vascular disease via metabolic disorder of lipoproteins, lipid peroxidation and oxidative stress.

Biochemical and histological evaluation of kidney damage after sub-acute exposure to 2,4-dichlorophenoxyacetic herbicide in rats: involvement of oxidative stress.

The present study evaluated the effects of sub-acute exposure to different doses of 2,4-dichlorophenoxyacetic acid (2,4-D) on rat kidney. Forty animals were divided into four equal groups and treated with different doses of 2,4-D: 0, 15, 75 and 150 mg/kg body weight per day via oral gavage for 28 consecutive days. Renal function, histopathology, tissue malondialdehyde and antioxidant enzyme activities were evaluated. The results showed a significant decrease (p < 0.01) in uric acid level and an increase in plasma levels of urea and creatinine (p < 0.01) in rats administered 2,4-D at the three studied doses. The activities of catalase and superoxide dismutase were significantly affected for all treated rats, while glutathione peroxidase significantly decreased in rats exposed to 2,4-D at a dose of 150 mg/kg. Through sub-acute treatment, starting from the low to the high doses of 2,4-D, there were significant increase in kidney MDA as compared to controls. The histopathological study revealed tubular damages, glomerular alterations, vascular congestion and increased number of pyknotic nuclei in kidneys of all 2,4-D treated groups. The severity of these alterations increase in a dose-dependent manner. Our findings confirm that sub-acute exposure to 2,4-D induced oxidative renal dysfunction in rats. Therefore, at higher doses, 2,4-D may be implicated in the pathogenesis of kidney failure via lipid peroxidation and oxidative stress.

Hypolipidimic and antioxidant activities of virgin olive oil and its fractions in 2,4-diclorophenoxyacetic acid-treated rats.

OBJECTIVE: We examined the effects of extra virgin olive oil (EVOO) and its hydrophilic and lipophilic fractions on serum lipids, oxidative stress, and morphologic and functional liver damages induced by 2,4-diclorophenoxyacetic acid (2,4-D). METHODS: Male Wistar rats were divided randomly into eight groups: control; 2,4-D at a dose of 5 mg/kg of body weight (2,4-D); 2,4-D plus EVOO (2,4-D/EVOO); 2,4-D plus the hydrophilic fraction (2,4-D/OOHF); 2,4-D plus the lipophilic fraction (2,4-D/OOLF); only EVOO (EVOO); only the hydrophilic fraction (OOHF); and only the lipophilic fraction (OOLF). These components were administered daily by gavage for 4 wk. RESULTS: A hepatic architecture aberration, increased activities of aspartate and alanine aminotransferase enzymes, total and low-density lipoprotein cholesterol, and malondialdehyde (MDA) level, and a decreased antioxidant defense system were observed in the 2,4-D group. The administration of EVOO restored the damage caused by 2,4-D by a significant decrease of plasma total and low-density lipoprotein levels and a moderate increase of high-density lipoprotein cholesterol. The 2,4-D/OOHF group exhibited a pronounced enhancement of the antioxidant defense system by an increase of superoxide dismutase, catalase, and glutathione peroxidase levels and a decrease of plasma and liver MDA levels. However, less improvement in the liver histoarchitecture and antioxidant status was observed in rats supplemented with OOLF diet, despite its richness in α-tocopherol. CONCLUSION: Extra virgin olive oil may be a potential functional food source of antioxidants than can decrease the frequency of cardiovascular diseases and liver damage.

[Association between oxidative stress parameters and inflammation markers according to the gravity of the acute coronary syndrome]. / Association entre les paramètres du stress oxydatif et les marqueurs de l'inflammation selon la gravité du syndrome coronaire aigu.

BACKGROUND: Cardiovascular disease is the consequence of appearance and development of atherosclerosis lesions of associated with a inflammatory complication. AIM: To elucidate a possible association between several inflammation and oxidative stress markers according to the severity of coronary artery disease. METHODS: This study was carried on 93 coronary subjects with: unstable angina (UA; n=42); stable angina (SA; n=15) and acute myocardial infarction (AMI; n=36) and 140 control subjects to whom lipidic, oxidative and inflammatory parameters were determined. RESULTS: In addition to a moderate hyperhomocysteinemia observed in the coronary artery disease, a significant higher levels of the oxidized LDL (ox-LDL) were found among these patients (p< 0.001). A positive correlation was found between the markers of the inflammation and the gravity of the acute coronary syndrome. One note a significant increase of the rate of ox-LDL and high sensitive CRP to AMI by reports in UA and SA (p=0.00, and p=0.001 respectively) which is linked to an elevation of the plasmatic concentration of the total homocysteine. CONCLUSION: This study suggests an association between the markers of the inflammation and oxidative parameters in the acute coronary syndrome.

Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2,4-Dichlorophenoxyacetic acid-treated rats.

BACKGROUND: Olive oil's beneficial effects are not only related to its high content of oleic acid, but also to the antioxidant potential of its polyphenols. In this study, we assess the effects of virgin olive oil and its fractions on 2,4-D- induced oxidative damage in the liver of rats. METHODS: Male Wistar rats were randomly divided into eight groups of ten each: (C) a control group, (D) group that received 2,4-D (5 mg/kg b.w.), (D/EVOO) group treated with 2,4-D plus extra virgin olive oil, (D/OOHF) group that received 2,4-D plus hydrophilic fraction, (D/OOLF) group treated with 2,4-D plus lipophilic fraction, (EVOO) group that received only extra virgin olive oil, (OOHF) group given hydrophilic fraction and (OOLF) group treated with lipophilic fraction. These components were daily administered by gavage for 4 weeks. RESULTS: A significant liver damage was observed in rats treated with 2,4-D via increased serum levels of transaminases and alkaline phosphatase, hepatic lipid peroxidation and decreased hepatic antioxidant enzyme activities, namely, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The liver's fatty acid composition was also significantly modified with 2,4-D exposure. However, extra virgin olive oil and hydrophilic fraction intake during 2,4-D treatment induced a significant increase in the antioxidant enzyme activities and a decrease in the conjugated dienes (CD) and thiobarbituric acid-reactive substances (TBARs) levels in the liver. The lipophilic fraction supplemented to 2,4-D- treated rats did not show any improvement in the liver oxidative status while a marked improvement was detected in the hepatic fatty acid composition of rats supplemented with olive oil and the two fractions. CONCLUSION: We concluded that the protective effect of olive oil against oxidative damage induced by 2,4-D is mainly related to the antioxidant potential of its hydrophilic fraction.

Dietary olive oil effect on antioxidant status and fatty acid profile in the erythrocyte of 2,4-D- exposed rats.

BACKGROUND: Oxidative stress produced by reactive oxygen species (ROS) has been linked to the development of several diseases such as cardiovascular, cancer, and neurodegenerative diseases. This study investigates the possible protective effect of extra virgin olive oil (EVOO), lipophilic fraction (OOLF) and hydrophilic fraction (OOHF) on oxidative stress and fatty acid profile of erythrocytes in 2,4-D treated rats. METHODS: Male Wistar rats were divided randomly into eight groups: control (C), (2,4-D) at a dose of 5 mg/kg b.w., (2,4-D/EVOO) was given 2,4-D plus EVOO, (2,4-D/OOHF) that received 2,4-D plus hydrophilic fraction, (2,4-D/OOLF) treated with 2,4-D plus lipophilic fraction, (EVOO) that received only EVOO, (OOHF) was given hydrophilic fraction and (OOLF) treated with lipophilic fraction. These components were daily administered by gavages for 4 weeks. RESULTS: 2,4-D treatment lead to decrease of antioxidant enzyme activities, namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) associated with a higher amount of MDA level. Erythrocyte membranes' fatty acid composition was also significantly modified with 2,4-D exposure. EVOO and hydrophilic fraction supplemented to rats with or not 2,4-D treatment enhanced the antioxidant enzyme activities and reduced the MDA level. However, lipophilic fraction did not show any improvement in oxidative damage induced by 2,4-D in spite its richness in MUFA and vitamins. CONCLUSION: EVOO administered to 2,4-D-treated rats protected erythrocyte membranes against oxidative damage by means of preventing excessive lipid peroxidation to increase the MUFA composition and increase maintaining antioxidants enzymes at normal concentrations.

High density lipoprotein-anionic peptide factor effect on reverse cholesterol transport in type 2 diabetic patients with and without coronary artery disease.

OBJECTIVES: To verify if HDL3 Anionic Peptide Factor (HDL3-APF) is as an apolipoprotein that promotes the reverse cholesterol transport. DESIGN AND METHODS: We investigated a possible association between plasma HDL3-APF concentration, cholesterol efflux from Fu5AH cells and cholesteryl ester transfer protein (CETP) activity in type 2 diabetic patients with coronary artery disease (CAD) (n=36), those without CAD (n=20), and 37 healthy subjects. RESULTS: Plasma APF concentrations were decreased in diabetics with CAD compared to controls (p<0.01). Cellular cholesterol efflux was decreased in diabetics without and with CAD, (p<0.01 and p<0.001 respectively). CETP activity was significantly elevated in all patient groups. Multiple linear regression analysis shows that cholesterol efflux was independently and positively related only to APF concentrations in controls. CONCLUSIONS: APF is likely to be a key independent factor for promoting cellular cholesterol efflux in healthy subjects. However this association is altered in type 2 diabetes.

Genotypic interactions of renin-angiotensin system genes with diabetes type 2 in a Tunisian population.

AIMS: To explore the role of genetic variants of angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE I/D), and angiotensin type 1 receptor (AT1R A1166C) as predictors of diabetes risk and to examine their combined effects on type 2 diabetes mellitus (T2DM) patients. MAIN METHODS: One hundred and fourteen T2DM patients were compared to 175 healthy controls with similar age and sex. KEY FINDINGS: The genotypic frequencies for all three genes alone were significantly associated with increased risk of developing diabetes. Logistic regression analysis of classic coronary risk factors and the genetic polymorphisms demonstrated that hypertension and ACE DD genotype were the most significant contributors to T2DM. For the renin-angiotensin system (RAS) genes, the risk of T2DM in individuals with one risk genotype was 1.9 (95%CI: 1.1-3.0, p=0.017) higher than those with zero risk genotype. Individuals who carried two risk genotypes had a 4.0 (95%CI 1.7-9.4, p=0.001) times higher risk of T2DM than those who did not carry any risk genotypes of the RAS genes. Most interestingly, the risk of T2DM for individuals with three risk genotypes was 26.2 (95%CI: 5.8-117.9, p<0.001) higher than those with zero risk genotype. SIGNIFICANCE: The results of the present study imply that genotyping of renin-angiotensin system genes could become an important part of the clinical process of risk identification for T2DM in Tunisian population.

Association of the C677T MTHFR polymorphism with homocysteine, ox-LDL levels, and thiolactonase activities in the severity of coronary syndrome.

Coronary artery diseases (CAD) are influenced by multiple genes of modest effect as the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, related to MTHFR activity and total plasma homocysteine (tHcy) concentration. This study was designed to evaluate tHcy, oxidized low-density lipoprotein (LDL) (ox-LDL), high-sensibility C-reactive protein (Hs CRP) levels, and homocysteine thiolactonase (HTase) activities as new risk factors for CAD and to investigate an association between MTHFR polymorphism tHcy concentrations and coronary syndrome severity. Our results showed significantly higher levels of tHcy and ox-LDL in patients associated with lower HTase activities. These levels increased proportionally to disease severity. Total plasma Hcy levels were negatively correlated to HTase activities in patients where the TT genotype was significantly more frequent. In a multivariate analysis, tHcy level was the only independent factor affecting the coronary syndrome severity. High tHcy levels are associated with coronary syndrome severity and may be explained either by the elevated prevalence of TT genotype or by the diminished HTase activities.

Hepatotoxicity induced by sub-acute exposure of rats to 2,4-Dichlorophenoxyacetic acid based herbicide "Désormone lourd".

"Désormone Lourd" is a 2,4-Dichlorophenoxyacetic based herbicide that includes 600 g/L 2,4-D. In this study we analyzed the toxic effects of 2,4-D on rat liver. Animals were daily treated with 15, 75 and 150 mg/kg, via oral gavage during 4 weeks. Hepatotoxicity was monitored by quantitative analysis of the serum enzymes markers of hepatotoxicity. Oxidative stress markers, catalase and glutathione reductase (CAT and GR), were analyzed in liver. We also investigated liver tissues histopathologically. Our results revealed that, when rats of 2,4-D treated groups were compared with the control group, the body weight decreased and the liver weight increased significantly at the end of the 4th week. The microscopic evaluation showed that 2,4-D induced hepatic cord disruption, focal necrosis, vessel dilation and pycnotic nucleus. Histological effects were found in all treated groups and their severity was dose dependent. Through sub-acute treatment, starting from the low to the high doses of 2,4-D, it was observed that there were effects on the activity of the serum enzyme markers, on TSP, Alb and the glycemia levels. We also observed a significant reduction in the hepatic antioxidant enzyme activities. To conclude, we can suggest that 2,4-D induces hepatoxicity and cellular alterations in rat.

Screening of antileishmanial activity from marine sponge extracts collected off the Tunisian coast.

The present study reports on the in vitro antileishmanial activity of two Ircinidae (Dictyoceratida, Demospongiae, Porifera) Ircinia spinosula and Sarcotragus sp. Sampled from the east coast of Tunisia. The ethyl acetate, dichloromethane, and aqueous extracts were tested against Leishmania major promastigotes. The anti-proliferative activity was checked using different extracts concentration during 72 h. We found that the IC50 (sub-inhibitory concentration) values ranged from 1.39 to 264.67 mug/ml. The most active extract was that from sarcotragus sp dichloromethane extract. Microscopic observations showed that the extracts promoted cellular alterations and induce enlargement of the nucleus and modification of the parasite shape. These promising results in relation with in vitro antileishmanial activity open the way for complementary investigation in order to purify and identify active molecules.

Relationship between genetic polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase as risk factors for type 2 diabetes in Tunisian patients.

BACKGROUND/AIMS: The role of methylenetetrahydrofolate reductase (MTHFR) and angiotensin-converting enzyme (ACE) gene polymorphisms as being risk factors for diabetes is still controversial. The aim was to investigate the distribution of ACE and MTHFR genotypes as well as to evaluate the role of plasmatic total homocysteine levels (tHcy) and ACE activity in Tunisian patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: 115 T2DM patients compared to 116 healthy volunteers. RESULTS: The ACE I/D polymorphism was significantly associated with diabetes (p<0.0001). The DD genotype and D allele were more frequent in patients compared to control group [DD: OR=4.93; p<0.0001; 95 % CI: 2.71-8.97; D: OR=3.08, 95% CI: 2.09-4.51 p<0.0001]. MTHFR allele and genotype frequencies did not differ between patients and controls. The susceptibility to diabetes in individuals with genotypes DD+vTT was 13.39 and in the individuals with DD+CT was 6.57 times that of the controls. However, individuals with genotypes ID+CC or II+CT have a protective effect against diabetes. The DD and TT genotypes were associated with significantly higher ACE activity and tHcy levels in diabetics. CONCLUSION: Our data suggest that ACE ID polymorphism may act synergistically with MTHFR C677T polymorphism to assess diabetes risk.

Investigation of several virulence properties among Vibrio alginolyticus strains isolated from diseased cultured fish in Tunisia.

We analysed 34 Vibrio alginolyticus strains isolated from gilthead sea bream Sparus aurata L. and sea bass Dicentrarchus labrax L. cultured in fish farms on the Tunisian Mediterranean coast for the presence of several virulence properties such as extracellular products (ECP) production, growth in iron-limiting conditions and survival in fish serum. The results obtained with different substrates showed that ECP of V. alginolyticus were hydrolytic. The virulence was correlated with the ability of strains to grow in the presence of non-immune fish serum or under conditions of iron limitation. We further examined the presence of virulence genes homologous to those in V. cholerae (toxR, toxS, VPI and ace); toxR was found in 16 V. alginolyticus strains and toxS in 17 strains out of 34 analysed. A positive amplification for the virulence pathogenicity island (VPI) was produced by 12 V alginolyticus strains. Finally, the ace expected amplification fragment was found in 7 V. alginolyticus isolates. Thus, the pathogenicity of V. alginolyticus may be the result of a combination of all these factors.

Association of homocysteine thiolactonase activity and PON1 polymorphisms with the severity of acute coronary syndrome.

INTRODUCTION: Excess of total homocysteine (tHcy) and decrease of thiolactonase activities (HTase) have been proposed as risk factors for coronary artery diseases (CAD). OBJECTIVES: We evaluated the relationship of tHcy and HTase with paraoxonase 1 (PON1) gene polymorphism according to CAD severity. DESIGN AND METHODS: 118 healthy volunteers and 91 CAD patients were compared. RESULTS: Serum levels of tHcy and oxidized LDL (ox-LDL) increased significantly by 26% and 48% in CAD patients and were associated with significantly lower levels of HDL cholesterol (p=0.02) and 42% of decrease in HTase activities (p<0.05). In these patients the HTase activity was negatively associated with tHcy and Hs CRP levels (r=-0.622, p=0.00 and r=-0.355, p=0.007 respectively) but positively associated with apoB and triglyceride levels (r=0.35, p=0.042 and r=0.308, p=0.003 respectively). HTase activity decreased inversely to the number of affected vessels and according to PON1 polymorphism. PON1 Q192R RR and PON1 L55M MM genotypes were associated with higher HTase activities. Only PON1 L55M (MM) genotype frequency was significantly higher in CAD patients than in controls (P<0.05), while its frequency was similar between the two subgroups according to CAD severity. In a multivariate analysis, tHcy levels were the only independent factor affecting the severity of cardiovascular disease (p=0.029). CONCLUSIONS: High tHcy levels are associated with the severity of cardiovascular disease and may be partly explained by the diminished HTase activities in these patients.

Reverse modulation of the HDL anionic peptide factor and phospholipid transfer protein activity in coronary artery disease and type 2 diabetes mellitus.

OBJECTIVES: The high density lipoprotein Anionic Peptide Factor (HDL(3)-APF) was previously described as an apolipoprotein that promotes the reverse cholesterol transport. Since phospholipid transfer protein (PLTP) is involved in such mechanism we attempted to focus on the two APF and PLTP proteins. DESIGN AND METHODS: We recruited 56 type 2 diabetic patients with (n=36) or without (n=20) coronary artery disease (CAD) and 19 CAD patients. The three groups were compared to 39 healthy control subjects. In all groups, lipid profile was determined and plasma APF concentrations and PLTP activity were measured. RESULTS: In all patients, the PLTP activity was significantly increased in comparison with controls (p<0.01), in concomitance with a plasma APF level decrease in groups with CAD (with and without type 2 diabetes) (p<0.01). Multiple linear regression analysis demonstrated that, when apoA-I, HDL-C, HDL-phospholipids and PLTP activity were taken into account as independent variables (after univariate regression analysis), HDL-PL was positively and independently related to APF (p<0.0001 in whole population; p=0.0090 in controls) and PLTP activity was negatively and independently related to APF in whole population and all patients' groups (all p<0.05), but positively and independently associated to APF in controls (p=0.0005). CONCLUSIONS: APF could be considered as a specific marker against CAD and type 2 diabetes mellitus and our results confirm the atherogenic behavior of PLTP in CAD. Thus, these two proteins are likely to be regulated in a reverse manner.