Plasma Lipid Parameters Research Articles

Should diabetic ketosis without acidosis be included in ketosis‐prone type 2 diabetes mellitus?

The incidence of ketosis-prone type 2 diabetes is very low except for people of sub-Saharan African origin and African Americans. However, there also are some type 2 diabetes patients with diabetic ketosis without acidosis (DKWA). We question whether DKWA should be included as a subtype of ketosis-prone type 2 diabetes mellitus and compared the clinical characteristics of DKWA and diabetic ketoacidosis (DKA) patients. The study population consisted of 594 consecutive unrelated Chinese inpatients with newly diagnosed type 2 diabetes. Demographic and clinical characteristics (age, gender, family history of diabetes, body mass index, blood pressure and plasma lipid parameters) were recorded. The patients were divided into ketosis-resistant diabetes (KRD), DKWA and DKA groups on the basis of urinary ketones, blood pH and bicarbonate levels. The blood glucose and c-peptide levels of the patients were also evaluated. The prevalence of KRD, DKWA and DKA were 78.33%, 19.72% and 1.95%, respectively, in the study population. The clinical characteristics of patients with DKWA group patients were similar to those with DKA, except that DKA patients had higher blood glucose and deteriorated β cell function. Diabetic ketosis without acidosis and DKA patients share similar clinical characteristics; DKWA should be considered ketosis-prone type 2 diabetes. Therefore, the prevalence of ketosis-prone type 2 diabetes might be underestimated.

Effects of a farnesoid X receptor antagonist on hepatic lipid metabolism in primates

We aimed to elucidate the mechanism underlying the anti-dyslipidemic effect of compound-T3, a farnesoid X receptor antagonist, by investigating its effects on hepatic lipid metabolism in non-human primates. We administered lipid-lowering drugs for 7 days to cynomolgus monkeys receiving a high-fat diet, and subsequently measured the levels of lipid parameters in plasma, feces, and hepatic tissue fluids. Compound-T3 (0.3 and 3mg/kg p.o.) significantly decreased the plasma levels of non-high-density lipoprotein (non-HDL) cholesterol and apolipoprotein B in a dose-dependent manner. It also decreased the mRNA levels of hepatic small heterodimer partner-1, induced the mRNA expression of hepatic cholesterol 7α-hydroxylase, reduced hepatic cholesterol and triglyceride levels, increased fecal bile acid excretion, and upregulated the expression of hepatic low-density lipoprotein (LDL) receptor. Furthermore, compound-T3 significantly increased plasma HDL cholesterol and apolipoprotein A-I levels. The mRNA expression levels of hepatic apolipoprotein A-I tended to increase after compound-T3 treatment. Compound-T3 also induced accumulation of hepatic bile acids and decreased the mRNA expression levels of the hepatic bile acid export pump. The effects of cholestyramine (300mg/kg p.o.) on the plasma and hepatic lipid parameters were similar to those of compound-T3, and it increased fecal bile acid levels without causing accumulation of hepatic bile acids. These findings suggest that LDL receptor-mediated hepatic LDL incorporation due to cholesterol catabolism catalyzed by cholesterol 7α-hydroxylase decreases plasma non-HDL cholesterol levels. Upregulation of hepatic apolipoprotein A-I mRNA expression may partially contribute to the increase in HDL cholesterol levels mediated by compound-T3.

The Impact of Fasting during Ramadan on the Glycemic Control of Patients with Type 2 Diabetes Mellitus

Millions of Muslims fast from dawn until dusk during the annual Islamic holy month of Ramadan. Most of the studies evaluating biochemical changes in diabetic patients during Ramadan showed little changes in the glycemic control. In this study, our aim was to assess the impact of fasting during Ramadan on glycemic control in patients with type 2 diabetes. We examined 122 patients with type 2 diabetes (82 female, 40 male, age 56.93 ± 9.57 years) before and after the Ramadan. 66.4% of the patients were treated with oral antidiabetic (OAD) alone, 6.5% with a combination of insulin plus OAD and 19.7% with insulin alone. 88 of 122 patients fasted during Ramadan (26.98 ± 5.93 days). Weight, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), postprandial glucose (PPG), fructosamine, HbA1c, fasting insulin and lipid parameters were measured. The frequencies of both severe hyperglycemia and hypoglycemia were higher in the fasting group, but the difference was not significant (p=0.18). Weight, BMI, waist circumference, blood pressure, FPG (143.38 ± 52.04 vs. 139.31 ± 43.47 mg/dl) PPG (213.40 ± 98.56 vs. 215.66+109.31 mg/dl), fructosamine (314.18 ± 75.40 vs. 314.49 ± 68.36 µmol/l), HbA1c (6.33 ± 0.98 vs. 6.22 ± 0.92%) and fasting insulin (12.61 ± 8.94 vs. 10.51 ± 6.26 µU/ml) were unchanged in patients who fasted during Ramadan. Microalbuminuria significantly decreased during Ramadan (132.85 ± 197.11 vs. 45.03 ± 73.11 mg/dl). In this study, we concluded that fasting during Ramadan did not worsen the glycemic control of patients with type 2 diabetes.

Monitoring of Lipids, Enzymes, and Creatine Kinase in Patients on Lipid-Lowering Drug Therapy

A number of plasma lipid parameters have been used to estimate cardiovascular risk and to be targets for treatment to reduce risk. Most risk algorithms are based on total cholesterol (T-C) or low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and most intervention trials have targeted the LDL-C levels. Emerging measures, which in some cases may be better for risk calculation and as alternative treatment targets, are apolipoprotein B and non-HDL-C. Other lipid measures that may contribute in risk analysis are triglycerides (TG), lipoprotein(a), and lipoprotein-associated phospholipase A2. The primary treatment target in cardiovascular prevention is LDL-C, and potential alternative targets are apoB and non-HDL-C. In selected individuals at high cardiovascular (CV) risk, TG should be targeted, but HDL-C, Lp(a), and ratios such as LDL-C/HDL-C or apoB/apoAI are not recommended as treatment targets. Lipids should be monitored during titration to targets. Thereafter, lipids should be checked at least once a year or more frequently to improve treatment adherence if indicated. Monitoring of muscle and liver enzymes should be done before the start of treatment. In stable conditions during treatment, the focus should be on clinical symptoms that may alert muscle or liver complications. Routine measurement of CK or ALT is not necessary during treatment with statins.

The impact of fasting during Ramadan on the glycemic control of patients with type 2 diabetes mellitus

Background Millions of Muslims fast from dawn until dusk during the annual Islamic holy month of Ramadan. Most of the studies evaluating biochemical changes in diabetic patients during Ramadan showed little changes in the glycemic control. In this study, our aim was to assess the impact of fasting during Ramadan on glycemic control in patients with type 2 diabetes. Methods and design We examined 122 patients with type 2 diabetes (82 female, 40 male, age 56.93 ± 9.57 years) before and after the Ramadan. 66.4% of the patients were treated with oral antidiabetic (OAD) alone, 6.5% with a combination of insulin plus OAD and 19.7% with insulin alone. 88 of 122 patients fasted during Ramadan (26.98 ± 5.93 days). Weight, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), postprandial glucose (PPG), fructosamine, HbA1c, fasting insulin and lipid parameters were measured. Results The frequencies of both severe hyperglycemia and hypoglycemia were higher in the fasting group, but the difference was not significant (p=0.18). Weight, BMI, waist circumference, blood pressure, FPG (143.38 ± 52.04 vs. 139.31 ± 43.47 mg/dl) PPG (213.40 ± 98.56 vs. 215.66+109.31 mg/dl), fructosamine (314.18 ± 75.40 vs. 314.49 ± 68.36 µmol/l), HbA1c (6.33 ± 0.98 vs. 6.22 ± 0.92%) and fasting insulin (12.61 ± 8.94 vs. 10.51 ± 6.26 µU/ml) were unchanged in patients who fasted during Ramadan. Microalbuminuria significantly decreased during Ramadan (132.85 ± 197.11 vs. 45.03 ± 73.11 mg/dl). Conclusions In this study, we concluded that fasting during Ramadan did not worsen the glycemic control of patients with type 2 diabetes.

Omega-3 fatty acids, polymorphisms and lipid related cardiovascular disease risk factors in the Inuit population

BackgroundTissue concentrations of fatty acids (FAs) and genetic variations are well-known factors which affect the cardiovascular disease (CVD) risk. The objective was to examine whether the genetic variability of 20 candidate genes and red blood cells (RBCs) percentage of total n-3 polyunsaturated fatty acids (PUFA), a biomarker of dietary n-3 PUFA intake, modulate lipid related CVD risk factors in the Inuit population.MethodsData from the Qanuippitaa Nunavik Health Survey (n = 553) were analysed via multivariate regression models with 40 known polymorphisms, RBCs percentage of n-3 PUFA, and the interaction term to take into account the effect on plasma lipid and apolipoporotein levels.ResultsIndividuals being heterozygotes for CETP C-4502T (rs183130) or G-971A (rs4783961) together with higher n-3 PUFA had lower triacylglycerol (TG) concentrations compared to homozygotes for the minor allele. Further, effects of a stronger beneficial association between n-3 PUFA in RBCs and plasma lipid parameters- including lower total cholesterol (TC), lower low-density lipoprotein cholesterol (LDL-C) or higher high-density lipoprotein cholesterol (HDL-C) concentrations- were associated with AGT M235T (rs699) TT genotype, CETP G-971A (rs4783961) AG genotype, T allele carriers of CETP C-4502T (rs183130), and T allele carriers of CETP Ile405Val (rs5882). In contrast, higher n-3 PUFA in RBCs were associated with adverse lipid profiles- including increased LDL-C, increased apolipoprotein B100 or decreased HDL-C concentrations- in G allele carriers of the APOA5 -3 A/G (rs651821), C allele carriers of APOA5 T-1131C (rs662799), G carriers of APOC3 SstI (rs5128) and G carriers of APOA4 Asn147Ser (rs5104).ConclusionOverall, these results suggest that percentage of total n-3 PUFA of RBCs are associated with lipids related CVD risk factors conferred by genetic variations in the Inuit population.

Plasma PCSK9 Is a Late Biomarker of Severity in Patients With Severe Trauma Injury

PCSK9 (proprotein convertase subtilisin kexin type 9) is a secreted protease that modulates cholesterol homeostasis by decreasing low-density lipoprotein receptor expression. Low levels of plasma lipoproteins are related to severity of illness and survival in patients of intensive care units (ICU). The aim of the study was to investigate the regulation of plasma PCSK9 and its association with plasma lipid parameters and clinical markers of severity during critical illness. The plasma biobank from the previously published HYPOLYTE prospective study was used to measure PCSK9 concentrations by ELISA at days 0 and 8 in 111 patients admitted to surgical ICU for severe multiple trauma. Patients were randomly assigned to hydrocortisone therapy or placebo. Plasma PCSK9 levels were increased by 2-fold between days 0 and 8 (231 ± 116 vs 481 ± 227 ng/ml; P = .0001). Hydrocortisone therapy did not alter PCSK9 concentrations (451 ± 216 vs 511 ± 239 ng/ml in placebo group; P = .33). PCSK9 was positively associated with low-density lipoprotein-cholesterol (Pearson coefficient, 0.26; P = .007) at day 0, but not at day 8. At day 8, an inverse correlation was found between PCSK9 and high-density lipoprotein-cholesterol (β = -653; P = .004). Although baseline PCSK9 concentrations were not associated to severity scores, PCSK9 values at day 8 were related to injury severity score (β = 6.17; P = .0007), length of stay in ICU (β = 6.14; P = .0001), and duration of both mechanical ventilation (β = 8.26; P = .0001) and norepinephrine infusion (β = 18.57; P = .015). Plasma PCSK9 appears as a late biomarker of illness severity in patients with severe multiple trauma.

Resveratrol protects against atherosclerosis, but does not add to the antiatherogenic effect of atorvastatin, in APOE*3-Leiden.CETP mice

Resveratrol is a major constituent of traditional Asian medicinal herbs and red wine and is suggested to be a potential antiatherosclerotic drug due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate whether resveratrol protects against atherosclerosis development in APOE*3-Leiden.CETP (E3L.CETP) mice and adds to the antiatherogenic effect of mild statin treatment, currently the most widely used antiatherogenic therapy. E3L.CETP mice were fed a cholesterol-rich diet without (control) or with resveratrol (0.01% w/w), atorvastatin (0.0027% w/w) or both for 14 weeks. During the study plasma lipid, inflammatory and oxidative stress parameters were determined. Resveratrol reduced atherosclerotic lesion area (−52%) in the aortic root, comparable to atorvastatin (−40%) and the combination of both drugs (−47%). The collagen/macrophage ratio in the atherosclerotic lesion, a marker of plaque stability, was increased by resveratrol (+108%), atorvastatin (+124%) and the combination (+154%). Resveratrol decreased plasma cholesterol levels (−19%) comparable to atorvastatin (−19%) and the combination (−22%), which was completely confined to (very)low-density lipoprotein cholesterol levels in all groups. Post hoc analyses showed that the antiatherogenic effect of atorvastatin could be explained by cholesterol lowering, while the antiatherosclerotic effect of resveratrol could be attributed to factors additional to cholesterol lowering. Markers of inflammation and oxidative stress were not different, but resveratrol improved macrophage function. We conclude that resveratrol potently reduces atherosclerosis development and induces a more stable lesion phenotype in E3L.CETP mice. However, under the experimental conditions tested, resveratrol does not add to the antiatherogenic effect of atorvastatin.

Effect of a high-fructose diet on glucose tolerance, plasma lipid and hemorheological parameters during oral contraceptive administration in female rats

Oral contraceptive (OC) use and increased fructose feeding have been associated with altered cardiometabolic effects. The effect of increased dietary fructose during OC use on cardiometabolic parameters is unknown. We investigated the effects of a high-fructose diet on body weight gain, fasting blood glucose, glucose tolerance, plasma lipid and hemorheological parameters in female rats treated with a combination of OC steroids (norgestrel/ethinyl estradiol; NEE). Rats were given (p.o.) vehicle, high-dose NEE (10.0 μg norgestrel/1.0 μg ethinyl estradiol) or low-dose NEE (1.0 μg norgestrel/0.1 μg ethinyl estradiol) with or without high dietary fructose daily for 6 weeks. Results demonstrated that high-dose NEE but not low-dose NEE treatment led to significant increases in hematocrit, blood viscosity, and decreases in body weight gain, glucose tolerance, and plasma HDL-cholesterol level. Both NEE treatments resulted in significant increases in plasma viscosity and triglyceride. Increased dietary fructose without NEE treatment produced significant increases in fasting blood glucose, hematocrit, blood and plasma viscosities, while increased dietary fructose significantly potentiated the effects on blood and plasma viscosities observed during NEE treatment. Conversely, the effects of NEE treatment on body weight gain, glucose tolerance, plasma triglyceride and HDL-cholesterol were significantly attenuated. In conclusion, the results indicate that increase in dietary fructose may worsen abnormal blood rheology. The results also demonstrate that increased dietary fructose may not impact negatively on glucose and lipid metabolisms during OC use. The findings imply that fructose-enriched diet might be an important consideration during OC use regarding blood rheological properties.

Serum Calcium and Risk of Cardio Vascular Diseases with Menopause in North Indian Women

Menopause is a natural transition but has inconvenient effects on ageing women due to lack of health/ treatment awareness. Calcium supplements, which are commonly recommended to elderly people, particularly post menopausal women. Recent evidence warns that taking calcium supplements might increase myocardial infarction (MI) risk. We aimed to evaluate the relation of different biochemical and anthropometric parameters with baseline characteristic of postmenopausal women, related to risk of cardio vascular diseases (CVD). Correlation between fasting serum lipid profile [serum total cholesterol, serum triglyceride, serum HDL, (AIP; logTG/HDL)] with serum calcium and different anthropometric parameters in 200 menopausal women aged 45-56 years was studied retrospectively. All biochemical parameters were measured on fully automated analyser using standard reagent kits. History was taken through questionnaires from subjects with complains regarding menopause after taking verbal consent. In menopausal women between age 45-48 years when serum total cholesterol and serum triglyceride were in higher range and statically significant, at the same atherogenic index of plasma (AIP) was not significant, while above 48 years in age when serum calcium found to be in the normal range (8.7-11.0 mg/dl), atherogenic index of plasma (AIP) and serum lipid parameters show a statically significant relation to risk of CVD, and most of our subjects were unaware about menopausal symptoms and it’s treatment because of illiteracy. The counseling activity should go on complained regarding menopause with all anthropometric and biochemical parameters.

The distribution of apolipoprotein E gene polymorphism in Chinese civil aircrews, and a possible risk factor to their overweight and dyslipidemia is cumulative flight time

BackgroundThe prevalence of dyslipidemia and overweight is significantly higher in aircrews than that in general population. The purpose of the study was to examine the distribution of APOE gene polymorphism and the influence of which as well as occupational environment on dyslipidemia and overweight in Chinese civil aircrews. MethodsAPOE gene polymorphism was investigated using PCR-RFLP, plasma lipid parameters were measured by standard enzymatic kits and personal information of the aircrews was collected through questionnaires. ResultsThe allele frequencies among aircrews were ε2: 17.0%, ε3: 80.9%, and ε4: 2.1%, APOE gene polymorphism was associated with significant differences in TC and LDL-C. E2 individuals had the lowest TC and LDL-C concentrations, and E4 participants had the highest levels (p<0.001). In addition, the TC and LDL-C concentrations, as well as BMI rose with the increasing cumulative flying hours (p<0.05). The further logistic regression analysis showed the significant associations of BMI and dyslipidemia (p<0.0001, OR=2.093), cumulative flight time and overweight (p<0.0001, OR=1.560). ConclusionsThe distribution of APOE alleles among aircrews was provided for the first time, which is not fully identical with that among general population. These data also suggested the cumulative flight time influenced dyslipidemia and overweight as an environmental contributor.

Gene–diet interactions on plasma lipid levels in the Inuit population

The Inuit population is often described as being protected against CVD due to their traditional dietary patterns and their unique genetic background. The objective of the present study was to examine gene-diet interaction effects on plasma lipid levels in the Inuit population. Data from the Qanuippitaa Nunavik Health Survey (n 553) were analysed via regression models which included the following: genotypes for thirty-five known polymorphisms (SNP) from twenty genes related to lipid metabolism; dietary fat intake including total fat (TotFat) and saturated fat (SatFat) estimated from a FFQ; plasma lipid levels, namely total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and TAG. The results demonstrate that allele frequencies were different in the Inuit population compared with the Caucasian population. Further, seven SNP (APOA1 - 75G/A (rs670), APOB XbAI (rs693), AGT M235T (rs699), LIPC 480C/T (rs1800588), APOA1 84T/C (rs5070), PPARG2 - 618C/G (rs10865710) and APOE 219G/T (rs405509)) in interaction with TotFat and SatFat were significantly associated with one or two plasma lipid parameters. Another four SNP (APOC3 3238C>G (rs5128), CETP I405V (rs5882), CYP1A1 A4889G (rs1048943) and ABCA1 Arg219Lys (rs2230806)) in interaction with either TotFat or SatFat intake were significantly associated with one plasma lipid variable. Further, an additive effect of these SNP in interaction with TotFat or SatFat intake was significantly associated with higher TC, LDL-C or TAG levels, as well as with lower HDL-C levels. In conclusion, the present study supports the notion that gene-diet interactions play an important role in modifying plasma lipid levels in the Inuit population.

Abstract 287: Plasma PCSK9 Concentrations in Critically Ill Patients

Objective. Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that impairs LDL clearance by promoting the LDL receptor (LDLR) degradation. Plasma lipid parameters (LDL-C and HDL-C) are related to severity of illness and survival in intensive care patients. Here, we aimed to determine whether circulating PCSK9 concentrations were correlated to the severity of illness in patients with multiple trauma. Methods/Results. Plasma PCSK9 were measured, at day 0 and 8 after admission, by ELISA in 111 patients hospitalized in ICU for severe trauma. Patients were included in the HIPOLYTE study and were randomly assigned to hydrocortisone therapy or placebo. Plasma PCSK9 levels were significantly increased by 161% at day 8 compared to day 0 (481 ± 227 vs 231 ± 117 ng/ml, P=0.0001). Hydrocortisone therapy did not alter PCSK9 concentrations at day 8 compared to placebo (451 ± 216 vs 511 ± 239ng/ml, P=0.33). In the whole population of the study, PCSK9 was positively associated with LDL-C (Pearson coefficient : 0.26, p=0.007) at day 0, but not with markers of severity illness. At day 8, an inverse correlation was found between PCSK9 and HDL-C (β =-653 ; P=0.004). Interestingly, PCSK9 concentrations at day 8 were related to markers of severity illness as injury severity score (β =6.17 ; P=0.0007), length of stay in ICU (β =6.14 ; P=0.0001), duration of both mechanical ventilation (β =8.26 ; P=0.0001) and cathecolamines infusion (β =18.57; P=0.015). Conclusion. PCSK9 appears as a late biomarker of severity illness in patients hospitalized for multiple trauma in ICU. These results open new perspectives for a role of PCSK9 in critical illness.

Abstract 482: Peroxisome Proliferator-Activated Receptor α Modulation with Fenofibrate Does Not Alter the Clinical or Inflammatory Responses to Evoked Endotoxemia in Humans

Introduction: Inflammation plays a crucial role in the pathophysiology of cardiometabolic disease. Some experimental data and clinical trials suggest that PPAR-α activation and fibrate therapy suppress inflammation in humans, potentially promoting anti-atherogenic actions. Human experimental endotoxemia provides a controlled model for the study of atherogenic inflammatory responses and their modulation in vivo . We hypothesized that fenofibrate would suppress the inflammatory responses to endotoxin (LPS) in healthy humans. Methods: In the Fenofibrate and Omega-3 Fatty Acid Modulation of Endotoxemia study, 36 healthy volunteers (mean age 26 ± 7 years; mean BMI 24 ± 3 kg/m 2 ; 56% male; 72% Caucasian, 19% African, 8% Asian ancestry) were randomized to fenofibrate 145 mg or placebo daily. After 8 weeks of treatment, subjects underwent a low-dose LPS challenge (0.6 ng/kg intravenous bolus). Anthropometric, clinical, and blood measures were collected at baseline, pre-LPS, and serially for 24 hours after LPS exposure. Results: Compared to placebo, fenofibrate reduced total cholesterol (170 ± 35 to 137 ± 31 mg/dL, p=0.009) and tended to decrease triglycerides (78 ± 40 to 57 ± 23 mg/dL, p=0.611) prior to LPS. LPS induced a modest clinical response with increased temperature, heart rate, and blood pressure ( p &lt;0.001 for all). Cytokines and chemokines increased significantly, peaking 2 to 4 hours post-LPS (TNFα 12-fold, IL-6 13-fold, IL-10 9-fold, MCP-1 10-fold; p &lt;0.001 for all). Acute phase reactants also increased, peaking at 24 hours (serum amyloid A (SAA) 14-fold, C-reactive protein (CRP) 9-fold; both p &lt;0.001). Compared to placebo, fenofibrate had no effect on LPS-induced clinical responses, cytokine or chemokine release as measured by peak response or area under the curve (AUC). Fenofibrate also had no effect on plasma CRP or lipid parameters following LPS. Although peak SAA and SAA AUC tended to be lower with fenofibrate vs. placebo, the differences were not statistically significant ( p =0.08 for both). Conclusions: PPAR-α modulation with fenofibrate did not attenuate clinical or inflammatory responses during low-grade human endotoxemia. These data suggest the anti-inflammatory properties of fenofibrate at clinically-relevant dosing are limited.

The effect of bone marrow transplantation on oxidative stress in X-linked adrenoleukodystrophy

Oxidative stress plays an important role in the pathophysiology of neurodegenerative diseases, including X-linked adrenoleukodystrophy (X-ALD). In the present work, we evaluated lipid (malondialdehyde [MDA] content) and protein (sulfhydryl and carbonyl contents) oxidative damage parameters in plasma from X-ALD patients before and after bone marrow transplant (BMT), in order to verify if this treatment is capable to alter the oxidative parameters studied. We also evaluated the plasma concentration of hexacosanoic acid (C26:0) from X-ALD patients and correlated it with the oxidative damage parameters investigated. We observed that MDA content was significantly increased in plasma of X-ALD patients before BMT and after BMT when compared to controls, and that it was significantly reduced in plasma of X-ALD after BMT when compared to the before BMT group. These results indicate that lipid peroxidation is stimulated in X-ALD patients but there is a significant reduction of lipid peroxidation after BMT. Next, we observed a significant reduction of sulfhydryl content in plasma of X-ALD patients before BMT compared to controls indicating protein oxidative damage and that this measurement was increased in these patients after BMT as compared to before BMT. We found no significant differences in plasma carbonyl content in X-ALD patients before and after BMT as compared to controls. However, we observed a significant reduction in this parameter in X-ALD patients after BMT compared to before BMT. Finally, C26:0 plasma concentration was significantly reduced in X-ALD patients after BMT when compared to before BMT. We found no significant correlations between MDA and carbonyl values with C26:0 levels of the patients before BMT and after BMT, but a significant inverse correlation between sulfhydryl content and C26:0 levels was detected. In conclusion, the present study reinforces the hypothesis that lipid peroxidation and protein damage are induced in plasma of X-ALD patients and, in addition, demonstrates that BMT treatment is capable to reduce this pathogenic process. Taken together, the data obtained from plasma of X-ALD patients before and after BMT showing induction and protection, respectively, of oxidative stress, allowed to suggest that BMT, when well succeeded and under the recommendations, is effective to reduce C26:0 plasma levels and the increased lipid and protein oxidative damage in X-ALD.

Cardioprotective Effects of Diet with Different Grains on Lipid Profiles and Antioxidative System in Obesity-Induced Rats

In the present study, the nutritional quality of four grains including adlay (AD), buckwheat (BW), glutinous barley (GB), and white rice (WR) were evaluated in terms of plasma lipid parameters, gut transit time, and thickness of the aortic wall in rats. The rats were then raised for 4 weeks on the high-fat diet based on the American Institute of Nutrition-93 (AIN-93 G) diets containing 1 % cholesterol and 20 % dietary lipids. Forty male rats were divided into 4 groups and raised for 4 weeks with a diet containing one of the following grains: WR, AD, BW, or WB. The level of thiobarbituric acid-reactive substances (TBARS) in liver was shown to be higher in rats by the order of those fed WR, AD, GB, and BW. This indicates that other grains decreased oxidative stress in vivo more than WR. The superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase levels in the AD, BW, and GB groups were significantly higher than those in the WR group (p < 0.05). Plasma lipid profiles differed significantly according to grain combination, and decreased aortic wall thickness was consistent with the finding of decreased plasma low-density lipoprotein cholesterol (LDL-C) (p < 0.05) and increased high-density lipoprotein (HDL-C) in rats fed AD, BW, and GB (p < 0.001). The antioxidant and hypolipidemic capacities of grains are quite high, especially those of adlay, buckwheat, and glutinous barley. In conclusion, this study has demonstrated that the whole grains had a cardioprotective effect. This effect was related to several mechanisms that corresponded to lowering plasma lipids, decreasing TBARS, and increasing antioxidant activities.

In comparison with palm oil, dietary nut supplementation delays the progression of atherosclerotic lesions in female apoE-deficient mice

Epidemiological studies have demonstrated the benefits of nut consumption on cardiovascular risk factors and CHD, attributed to their fatty acid profile, rich in unsaturated fatty acids, and also to other nutrients. The effect of nuts on atherosclerotic lesions was studied in female and male apoE-knockout mice fed a diet supplemented with 3 % (w/w) mixed nuts (mix: almonds, hazelnuts and walnuts in a proportion of 0.25:0·25:0.50, respectively), and compared with mice receiving an isoenergetic diet of similar fat content provided as palm oil. After 12 weeks, plasma lipid parameters and aortic lesions were measured. Males receiving nuts had lower plasma cholesterol than the palm oil group, and both sex groups had lower plasma non-HDL-cholesterol and lower content of reactive oxygen species in LDL than mice receiving the palm oil diet, the latter decrease being more pronounced in females than in males. Females consuming the nut diet showed a smaller aortic lesion area than those consuming palm oil, whereas no differences were observed in males. In females, hepatic paraoxonase 2 (Pon2) mRNA increased, and no change was observed in prenylcysteine oxidase 1 (Pcyox1) expression after the consumption of the nut-containing diet. In addition, aortic atherosclerotic lesions correlated directly with total plasma cholesterol and inversely with hepatic Pon2 expression. The results suggest that the beneficial effect of nut intake in female apoE-deficient mice may be attributed to reduced non-HDL-cholesterol levels and enhanced PON2 antioxidant activity.

Effect Some Medicinal Plants Diets on Mono Sex Nile Tilapia (Oreochromis niloticus), Growth Performance, Feed Utilization and Physiological Parameters

Thirteen experimental diets containing 30% crude protein and 438.09 Kcal gross energy/100g were formulated to contain six different medical plants fenugreek meal (FM),Trigonella foenum-graecum; fenugreek sprouts meal (FSM); eucalyptus fresh leaves (EFL), Eucalyptus citriodora; hot pepper meal (HPM) Capsicum frutescens L. var. abbreviatum; thyme seeds meal (TSM) Thymus vulgaris and chamomile flowers meal (CFM), Matricaria recutita Lat three different levels (0.00; 1.00 and 2.00%) from each of such medicinal plant on the growth performance,feed utilization and whole body composition and physiological parameters of Nile tilapia Oreochromis niloticus fry. Fish were reared in twenty six glass aquaria with an average initial weight of 0.82 ± 0.3g/fish. The results of the present study illustrated that the averages of growth performance and feed utilization values as affected with medicinal plant sources indicate that FSM showed the highest growth performance and feed utilization values (P≤0.05) followed in a significant decreasing order by fenugreek meal (FM) and eucalyptus fresh leaves (EFL) then by hot pepper meal (HPM)and both Thyme meal (TM) and Chamomile flowers meal (CFM),respectively. Regardless of medicinal plants sources, The analysis of variance for medicinal plant levels (MPL) indicate that supplementation level of 1% revealed significant (P≤0.05) the highest growth performance and feed utilization values followed in a significant (P≤0.05) decreasing order by 0.00 and 2.00% level,respectively. Concerning the interaction between medicinal plants sources and their levels (0.00,1.00 and 2.00%) the highest growth performance and feed utilization values (P≤0.05) were obtained by group 1% FSM (diet No.4),while the lowest was recorded by the group 2% TSM (diet No.11).On the other hand, the interactions between medicinal plants sources and their levels observed the lowest total plasma protein(g/dl), total plasma lipid (g/dl), Hb (g/dl), Ht (%), AST (U/L), ALT (U/L) and uric acid concentrations (mg/dl) parameters were obtained by group 1% FSM (diet No.4),while the highest parameters were recorded by the 2% TSM (diet No.11). In general, and based on the obtained results it could be concluded that addition of 1% LMP to the diet which contain FSM is considered optimal for growth of mono-sex Nile tilapia,O. niloticus,fingerlings without any adverse effect on fish health.

Studies on the euglycemic and hypolipidemic potentials of the novel indole analogue of thiazolidinedione, DRF 2189.

Euglycemic and hypolipidemic activities of a novel indole analogue of thiazolidinedione, DRF 2189 (CAS 172647-53-9), have been evaluated in different animal models. Compared to troglitazone (CAS 97322-87-7), DRF 2189 exhibited interesting plasma glucose and triglyceride lowering activity in genetically diabetic and obese db/db mice. It also produced a significant reduction in plasma glucose, triglyceride, total cholesterol levels and improvement in oral glucose tolerance in another genetic mouse model, the ob/ob mice. In high-fat diet fed Sprague-Dawley rats, DRF 2189 treatment showed improvement in plasma lipid parameters. Like other thiazolidinediones, this compound also possesses peroxisome proliferator activated receptor gamma (PPAR gamma) transactivation potential. In anaesthetized rat experiment, DRF 2189 produced a transient fall in blood pressure without any change in the ECG pattern. It showed non-specific smooth muscle relaxant activity against acetylcholine, histamine and potassium chloride induced contractions in isolated guinea pig ileum. A twenty-eight-day toxicity study in Wistar rats did not show any signs of treatment related adverse effects. The overall antidiabetic and hypolipidemic activities of DRF 2189 are comparable with rosiglitazone (CAS 155141-29-0) and superior to troglitazone. In conclusion, results from these preclinical studies indicate that DRF 2189, a novel thiazolidinedione, has a marked potential for the management of type-2 diabetes.

Antihyperlipedemic activity of Cynodon dactylon extract in high-cholesterol diet fed Wistar rats

The aim of the present study was to investigate the potential role of an ethanolic extract of the entire plant of Cynodon dactylon in lowering the plasma lipid parameters in rats fed a high cholesterol diet. Wistar albino rats were randomly divided into four groups of six and for 45 days were administered either: 0.5ml water (negative controls); 30mg cholesterol (hypercholesterolemic animals); C dactylon extract at 400mg/kg body weight (positive control); or the same doses of both cholesterol and the extract (test animals). The effects of C dactylon on the lipid profile were assessed by measuring the plasma concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and very low-density lipoprotein cholesterol (VLDL-c). Administration of cholesterol showed significant elevation (p<0.001) of TC, LDL-c, VLDL-c, and TG concentrations, and of the TC:HDL-c ratio (p<0.05). Concurrent administration of C dactylon extract caused a significant decrease (p<0.001) in the concentrations of serum TC, LDL, HDL, VLDL TGs when compared with cholesterol fed control rats. The TC:HDL-c ratio was also declined significantly (p<0.001). These results suggest lipid-lowering effects of C dactylon, which serves as a new potential natural product for preventing hyperlipidemia.