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BackgroundThe olive fly, Bactrocera oleae, is the most devastating pest of cultivated olives. Its control has been traditionally based on insecticides, mainly organophosphates and pyrethroids. In recent years, the naturalyte spinosad is used against the olive fly. As with other insecticides, spinosad is subject to selection pressures that have led to resistance development. Mutations in the α6 subunit of the nicotinic acetylcholine receptor (nAChR) have been implicated in spinosad resistance in several species (e.g., Drosophila melanogaster) but excluded in others (e.g., Musca domestica). Yet, additional mechanisms involving enhanced metabolism of detoxification enzymes (such as P450 monooxygenases or mixed function oxidases) have also been reported. In order to clarify the spinosad resistance mechanisms in the olive fly, we searched for mutations in the α6-subunit of the nAChR and for up-regulated genes in the entire transcriptome of spinosad resistant olive flies.ResultsThe olive fly α6-subunit of the nAChR was cloned from the laboratory sensitive strain and a spinosad selected resistant line. The differences reflected silent nucleotide substitutions or conserved amino acid changes. Additionally, whole transcriptome analysis was performed in the two strains in order to reveal any underlying resistance mechanisms. Comparison of over 13,000 genes showed that in spinosad resistant flies nine genes were significantly over-expressed, whereas ~40 were under-expressed. Further functional analyses of the nine over-expressed and eleven under-expressed loci were performed. Four of these loci (Yolk protein 2, ATP Synthase FO subunit 6, Low affinity cationic amino acid transporter 2 and Serine protease 6) showed consistently higher expression both in the spinosad resistant strain and in wild flies from a resistant California population. On the other side, two storage protein genes (HexL1 and Lsp1) and two heat-shock protein genes (Hsp70 and Hsp23) were unfailingly under-expressed in resistant flies.ConclusionThe observed nucleotide differences in the nAChR-α6 subunit between the sensitive and spinosad resistant olive fly strains did not advocate for the involvement of receptor mutations in spinosad resistance. Instead, the transcriptome comparison between the two strains indicated that several immune system loci as well as elevated energy requirements of the resistant flies might be necessary to lever the detoxification process.

Abstract Background The metabolic syndrome (MetS), as well as postprandial hypertriglyceridemia, is associated with coronary heart disease. This study aimed to evaluate the postprandial lipemia after oral fat tolerance test (OFTT) in subjects with MetS and compare them to hypertensive (HTN) and healthy subjects. Results OFTT was given to 33 men with MetS (defined by the Adult Treatment Panel III), 17 HTN and 14 healthy men. The MetS group was further divided according to fasting triglycerides (TG) into TG ≥ 150 [MetS+TG, (n = 22)] or The postprandial response was significantly higher in MetS compared to HTN and healthy men [AUC (SD) in mg/dl/h; 2534 ± 1016 vs. 1620 ± 494 and 1019 ± 280, respectively, p ≤ 0.001]. The TG levels were increased significantly in MetS+TG compared to MetS-TG subjects at 4 (p = 0.022), 6 (p < 0.001) and 8 hours (p < 0.001). The TG were increased significantly in MetS-TG compared to healthy subjects at 4 (p = 0.011), 6 (p = 0.001) and 8 hours (p = 0.015). In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 8.462, p < 0.001). Conclusion Fasting TG concentration is the main determinant of postprandial lipemia. However, an exaggeration of TG postprandialy was found in normotriglyceridemic MetS and HTN compared to healthy subjects. This suggests that intervention to lower fasting TG levels should be recommended in MetS subjects.

Telomeres, repetitive DNA sequences found at the ends of chromosomes, shorten with age in proliferating human tissues and are implicated in senescence. Previous studies suggest that shorter telomeres impair immune and cardiovascular function and result in increased mortality. Although few, prior studies have documented ethnic/population differences in human telomere lengths. The nature and cause(s) of these population differences remain poorly understood. Here, we extend the work of Salpea et al. () by reporting variation in mean blood telomere lengths (BTL) from 765 individuals from 14 study centers across 11 European countries. Subjects are male students (ages 18-28), half of whom had fathers with myocardial infarction before 55 and the remainder age-matched controls. Controlling for age and case-control status, telomere lengths averaged 10.20 kilobases (interpolated from qPCR measures) across study centers and ranged from 5.10 kilobases in Naples, Italy to 18.64 kilobases in Ghent, Belgium-a greater than threefold difference across populations. These population level differences in BTLs were neither explained by national level measures of population genetic structure nor by national level ecological analysis of indices of infection/economic status. These findings suggest considerable population variation in BTL in Europe that is not obviously a result of broad measures of population structure or infection/economic exposure measured in early life or in adulthood. Studying telomere dynamics in a wider variety of populations, and with greater attention to lifecycle dynamics, will be important to help elucidate the causes and possible consequences of human population variation in telomere length. Am. J. Hum. Biol., 2011. © 2011 Wiley-Liss, Inc [ABSTRACT FROM AUTHOR]

Objective:To replicate the associations of leukocyte telomere length (LTL) with variants at four loci and to investigate their associations with coronary heart disease (CHD) and type II diabetes (T2D), in order to examine possible causal effects of telomere maintenance machinery on disease aetiology. Methods:Four SNPs at three loci BICD1 (rs2630578 GγC), 18q12.2 (rs2162440 GγT), and OBFC1 (rs10786775 CγG, rs11591710 AγC) were genotyped in four studies comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs (rs12696304 CγG, rs10936601G>T and rs16847897 GγC) at the TERC locus were genotyped in these four studies, in addition to an offspring study of 765 healthy students. For all samples, LTL had been measured using a real-time PCR-based method. Results:Only one SNP was associated with a significant effect on LTL, with the minor allele G of OBFC1 rs10786775 SNP being associated with longer LTL (β=0.029, P=0.04). No SNPs were significantly associated with CHD or T2D. For OBFC1 the haplotype carrying both rare alleles (rs10786775G and rs11591710C, haplotype frequency 0.089) was associated with lower CHD prevalence (OR: 0.77; 95% CI: 0.61–0.97; P= 0.03). The TERC haplotype GTC (rs12696304G, rs10936601T and rs16847897C, haplotype frequency 0.210) was associated with lower risk for both CHD (OR: 0.86; 95% CI: 0.75-0.99; P=0.04) and T2D (OR: 0.74; 95% CI: 0.61–0.91; P= 0.004), with no effect on LTL. Only the last association remained after adjusting for multiple testing. Conclusion:Of reported associations, only that between the OBFC1 rs10786775 SNP and LTL was confirmed, although our study has a limited power to detect modest effects. A 2-SNP OBFC1 haplotype was associated with higher risk of CHD, and a 3-SNP TERC haplotype was associated with both higher risk of CHD and T2D. Further work is required to confirm these results and explore the mechanisms of these effects. [ABSTRACT FROM AUTHOR]

Background: The metabolic syndrome (MetS) is associated with an increased incidence of coronary heart disease (CHD). Postprandial hypertriglyceridaemia is also associated with CHD. The aim of this study was to evaluate the postprandial llipaemia after an oral fat tolerance test (OFIT) in women with MetS. Methods: OFTT was given to 21 menopausal women with MetS (defined by the Adult Treatment Panel III) and to 12 healthy menopausal women. Triglyceride (TG) levels were measured before and 2,4, 6 and 8 h after the OFTT. The postprandial response was quantified by the areas under the curve (AUC) of TG levels. MetS women were subdivided according to body mass index (BMI) < or ≥ 30 kg/m², and to fasting TG levels < or ≥ 150 mg/dL. Results: The response to the OFIT was significantly higher in the MetS group compared to healthy [AUC(S.D.), in mg/dL/h; 2014 (933) versus 732 (197), p < 0.001]. The subjects with BMI < or ≥ 30 kg/m2 had similar fasting TG levels [157 (60) mg/dL versus 158 (67) mg/dL] and AUC [1975 (898) versus 2072 (1044), respectively]. The MetS women with TG ≥ 150 mg/dL had higher AUC compared to those with TG < 150 mg/dL [2502 (854) versus 1281 (441), p =0.002]. In linear regression analysis, where BMI, high-density lipoprotein cholesterol, fasting TG, HOMA-IR and QUICKI were the independent variables, only fasting TGs significantly predicted the AUC (coefficient B = 11.866, p =0.008). Conclusions: The fasting TG concentration is the main determinant of postprandial lipaemia. The obesity state was not an additional determinant for exaggerated postprandial response in MetS women. The abnormal postprandial lipaemia could be added as an important metabolic disturbance to the MetS. [ABSTRACT FROM AUTHOR]

Purpose: Cholesteryl ester transfer protein (CETP) gene is involved in the reverse cholesterol transport in humans. Thus, it is a candidate for studying the susceptibility to coronary heart disease (CHD). The goal of the current investigation was to determine any association between CETP polymorphisms (I405V and TaqIB), and severity of coronary stenosis, since the extent of coronary artery narrowing has been considered as a primary determinant of survival in CHD patients. Methods: The severity of coronary stenosis was estimated by Gensini (GS) and Duke Jeopardy (JS) scores in 130 men with documented CHD (mean age 61 +/- 10 yr). Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism analysis. Results: The allele frequencies for both TaqIB and I405V were found in Hardy-Weinberg equilibrium. Homozygotes for I had lower GS compared with heterozygotes (IV) and homozygotes for V [72(95% CI 51-92) vs. 122(95% CI 88-157) and 136 (95% CI 74-198), P = 0.009, P = 0.010, respectively]. In addition, GS differed between carriers of I and carriers of V allele [86(95% CI 72-101) vs. 128(95% CI 102-154), P = 0.003]. A correlation was found between the GS and I405V polymorphism (r = 0.250, P = 0.005), but not with JS. Conclusion: Homozygosity for I405 favours less severe coronary stenosis. Our findings indicate that the I405V polymorphism may have potential importance in screening individuals at high risk for developing CHD, establishing efficient prevention measures, and searching for other risk factors for CHD. However, further prospective investigations in larger populations are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: To replicate the associations of leukocyte telomere length (LTL) with variants at four loci and to investigate their associations with coronary heart disease (CHD) and type II diabetes (T2D), in order to examine possible causal effects of telomere maintenance machinery on disease aetiology., Methods: Four SNPs at three loci BICD1 (rs2630578 GγC), 18q12.2 (rs2162440 GγT), and OBFC1 (rs10786775 CγG, rs11591710 AγC) were genotyped in four studies comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs (rs12696304 CγG, rs10936601G>T and rs16847897 GγC) at the TERC locus were genotyped in these four studies, in addition to an offspring study of 765 healthy students. For all samples, LTL had been measured using a real-time PCR-based method., Results: Only one SNP was associated with a significant effect on LTL, with the minor allele G of OBFC1 rs10786775 SNP being associated with longer LTL (β=0.029, P=0.04). No SNPs were significantly associated with CHD or T2D. For OBFC1 the haplotype carrying both rare alleles (rs10786775G and rs11591710C, haplotype frequency 0.089) was associated with lower CHD prevalence (OR: 0.77; 95% CI: 0.61-0.97; P= 0.03). The TERC haplotype GTC (rs12696304G, rs10936601T and rs16847897C, haplotype frequency 0.210) was associated with lower risk for both CHD (OR: 0.86; 95% CI: 0.75-0.99; P=0.04) and T2D (OR: 0.74; 95% CI: 0.61-0.91; P= 0.004), with no effect on LTL. Only the last association remained after adjusting for multiple testing., Conclusion: Of reported associations, only that between the OBFC1 rs10786775 SNP and LTL was confirmed, although our study has a limited power to detect modest effects. A 2-SNP OBFC1 haplotype was associated with higher risk of CHD, and a 3-SNP TERC haplotype was associated with both higher risk of CHD and T2D. Further work is required to confirm these results and explore the mechanisms of these effects.

Introduction: Previous studies of ours have shown that simvastatin (S) and nicotinic acid (NA) lower the alcohol (Alc)-induced increase of triglycerides. The aim of this study was to evaluate which drug is more effective and safe in decreasing Alc-induced hypertriglyceridaemia in Wistar rats., Methods: Male Wistar rats were randomised into 6 groups, which were fed with: (1) olive oil (Oil group, n=10); (2) Oil + Alc, (Alc group, n=10); (3) S solution in Oil (65 microg/100g body weight), (S group, n=10); (4) NA solution in Oil (8.5 mg/100g body weight), (NA group, n=8); (5) S solution in Oil + AIc (S+Alc group, n=10); and (6) NA solution in Oil + Alc (NA+Alc group, n=9). Another 13 male Wistar rats were fed only a standard laboratory diet (control group). After 8 weeks, blood samples were drawn and the livers were removed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total cholesterol (TC) and triglycerides (TG) were measured. Liver histopathology was also assessed., Results: Liver histopathology was similar in all groups and within the normal range. The TG plasma concentration in the Alc group was higher than in the control rats (p < 0.001) or any other groups (Oil, p < 0.001, or S, p < 0.001, or NA, p = 0.003). The Oil, S+Alc, NA+Alc and control groups had similar TG levels, but these were significantly lower compared to the Alc group (p < 0.001). AST plasma concentration was higher in the Alc group compared to controls (p < 0.001), Oil (p < 0.001), S (p < 0.001) and NA (p < 0.001) groups, while the AST concentration in the S+Alc and Na+Alc groups was lower than in the Alc group (p = 0.042, p < 0.001, respectively)., Conclusions: NA and S, two drugs of different classes, seem to decrease Alc-induced secondary hypertriglyceridaemia to the same extent. Moreover, NA displays a better alleviation of Alc-induced AST raises compared to S, although it enhances small increases in AP and ALT levels.

Introduction: The present investigation aimed to evaluate the influence of serum triglycerides (TG) on other plasma lipids in male patients less than 65 years of age intended for hypolipidaemic treatment., Methods: Lipid profiles of a cohort of 412 dyslipidaemic male patients aged 53.4 +/- 7.7 years (mean +/- standard deviation) were evaluated. Patients were stratified in accordance with their fasting plasma lipid levels. They were divided into multiple groups on the basis of serum TG (> or = 150 or < 150 mg/dl) and high-density lipoprotein cholesterol (HDL-C > or = 40 or < 40 mg/dl)., Results: Patients with TG > or = 150 mg/dl had higher total cholesterol and lower HDL-C levels compared with those with TG < 150 mg/dl (p = 0.005 and p < 0.001, respectively). Patients with HDL-C < 40 mg/dl had similar total cholesterol levels and higher TG levels compared to those with HDL-C > or = 40 mg/dl (p < 0.001). In all patients, an inverse correlation between TG and HDL-C was found (r = -0.286, p < 0.001). Additionally, HDL-C levels were inversely correlated with the TG concentration in patients with TG < 150 mg/dl (r = -0.135, p = 0.042) and TG > or = 150 mg/dl (r = -0.188, p = 0.002)., Conclusions: An inverse correlation between TG and HDL-C levels seems to exist in the sampled population, revealing a close link between the metabolic pathways for TG and HDL-C. This inverse correlation appears to persist even in patients with low fasting TG levels.

Introduction: The ingestion of alcohol (Alc) as well as gemfibrozil (Gem), a fibrate drug used to treat hypertriglyceridaemia, may occur on a long-term basis in humans. Since both Alc and Gem can disturb liver function, we assessed the effects of administering Alc together with Gem in Wistar rats., Materials and Methods: Male Wistar rats were randomized and divided into 4 groups of 10 each. They were fed (once a day) via a stomach tube with: i) 2 ml of polyethylene glycol (Peg); group Peg, ii) 2 ml of Peg + 2 ml of 25% v/v pure Alc in water; group Alc + Peg, iii) 2 ml of Gem solution in Peg (3.4 mg/100 g body weight); group Gem +Peg, iv) 2 ml of Gem solution in Peg 2 + 2 ml of Alc; group Gem +Alc +Peg. Another 13 male Wistar rats were only fed a standard laboratory diet (control group). After 8 weeks, blood samples were drawn and the livers removed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total cholesterol (TC) and triglycerides (TG) were measured. Liver histopathology was also assessed., Results: All tube-fed groups had higher body mass index compared to controls (p<0.001). The control group had lower AP compared to Gem+Peg and Gem +Alc+Peg groups (p=0.005 and p=0.018, respectively). The Peg group had lower AP compared to G+Peg (p=0.041). All tube-fed groups had lower ALT compared to controls (p<0.001). The TC levels were lower in tube-fed groups with Gem (Gem +Peg and Gem+Alc +Peg) compared to controls (p=0.002 and p=0.039, respectively). Among the tube-fed groups, the TC level was lower in Gem +Peg compared to Peg and Alc+Peg groups (p=0.047 and p=0.01, respectively). No differences were found among tube-fed groups and control rats in blood AST and TG. Liver histopathology was similar in all groups and within the normal range., Conclusion: A moderate amount of Alc daily together with Gem is safe in rats. Peg administration in Wistar rats protects from the Alc-induced TG and AST rises.