Toxicol Ind Health 2006 Mar; 22(2): 65-85 (Read article online)

Reed MD, Blair LF, Burling K, Daly I, Gigliotti AP, Gudi R, Mercieca MD, McDonald JD, O'Callaghan JP, Seilkop SK, Ronskoh NL, Wagner VO, Kraska RC

The U.S. Environmental Protection Agency's National Ambient Air Quality Standards for ozone and particulate matter (PM) require urban non-attainment areas to implement pollution-reduction strategies for anthropogenic source emissions. The type of fuel shown to decrease combustion emissions components versus traditional diesel fuel, is the diesel emulsion. The Lubrizol Corporation, in conjunction with Lovelace Respiratory Research Institute and several subcontracting laboratories, recently conducted a health assessment of the combustion emissions of PuriNOx diesel fuel emulsion (diesel-water-methanol) in rodents. Combustion emissions from either of two, 2002 model Cummins 5.9L ISB engines, were diluted with charcoal-filtered air to exposure concentrations of 125, 250 and 500 microg total PM/m3. The engines were operated on a continuous, repeating, heavy-duty certification cycle (U.S. Code of Federal Regulations, Title 40, Chapter I) using Rotella-T 15W-40 engine oil. Nitrogen oxide (NO) and PM were reduced when engines were operated on PuriNOx versus California Air Resources Board diesel fuel under these conditions. Male and female F344 rats were housed in Hazleton H2000 exposure chambers and exposed to exhaust atmospheres 6 h/day, five days/week for the first 11 weeks and seven days/week thereafter. Exposures ranged from 61 to 73 days depending on the treatment group. Indicators of general toxicity (body weight, organ weight, clinical pathology and histopathology), neurotoxicity (glial fibrillary acidic protein assay), genotoxicity (Ames assay, micronucleus, sister chromatid exchange), and reproduction and development were measured. Overall, effects observed were mild. Emulsion combustion emissions were not associated with neurotoxicity, reproductive/developmental toxicity, or in vivo genotoxicity. Small decreases in serum cholesterol in the 500-microg/m3 exposure group were observed. PM accumulation within alveolar macrophages was evident in all exposure groups. The latter findings are consistent with normal physiological responses to particle inhalation. Other statistically significant effects were present in some measured parameters of other exposed groups, but were not clearly attributed to emissions exposure. Positive mutagenic responses in several strains of Salmonella typhimurium were observed subsequent to treatment with emulsion emissions subfractions. Based on the cholesterol results, it can be concluded that the 250-microg/m3 exposure level was the no observed effect level. In general, biological findings in exposed rats and bacteria were consistent with exposure to petroleum diesel exhaust in the F344 rat and Ames assays.

Mol Cell Biochem 2006 May 23; (Read article online)

Raeder MB, Fernø J, Vik-Mo AO, Steen VM

Drug-induced weight gain is a major problem in the treatment of psychiatric disorders, especially with some antipsychotic- and antidepressant drugs. We have recently demonstrated that antipsychotic- and antidepressant drugs activate the SREBP (sterol regulatory element-binding proteins) transcription factors in human- and rat glial cells, with subsequent up-regulation of downstream genes involved in cholesterol- and fatty acid biosynthesis. Since stimulation of cellular lipogenesis in the liver could be of relevance for the metabolic side effects of these drugs, we have now investigated the effects of antidepressants, antipsychotic- and mood-stabilizing drugs on cell cultures of human liver cells. For several of the drugs being strongly associated with weight gain (clozapine, imipramine, and amitriptyline), we observed a very pronounced activation of SREBP. Ziprasidone and buproprion, however, which are not associated with weight gain, did hardly stimulate the SREBP system. For haloperidol, olanzapine and mirtazapine, the correspondence between metabolic side effects and SREBP stimulation in liver cells was less obvious. The mood-stabilizers did not increase SREBP activation. The results indicate a relationship between drug-induced activation of SREBP in cultured human liver cells and weight gain side-effects of antidepressant and antipsychotic drugs.

Inhal Toxicol 2006 Jul; 18(8): 575-9 (Read article online)

Ergüder IB, Ergüder T, Ozkan C, Bozkurt N, Soylu K, Devrim E, Durak I

The aim of this study was to compare short-term effects of smoking cessation on blood oxidant/antioxidant status, cholesterol levels, and paraoxonase activity. Sixteen healthy, asymptomatic long-term cigarette smokers (mean age: 35 +/- 9 yr) participated in the study in the smoking cessation program. After and before smoking cessation, subjects were examined for oxidant/antioxidant status, cholesterol level, paraoxonase activity, breath carbon monoxide levels, and blood carboxyhemoglobin values. When compared to previous values, subjects were revealed statistically significant decreases in malondialdehyde and carbon monoxide levels 4 wk after smoking cessation. The ratio of high-density lipoprotein (HDL) low-density lipoprotein (LDL) cholesterol was found to be increased. Significantly increased to paraoxonase activity was also observed in the bood samples obtained after cigarette cessation period. It was concluded that all these changes observed after smoking cessation might be of importance in the reduction of cardiovascular risk parameters in the smokers.

Biochem Biophys Res Commun 2006 May 15; (Read article online)

Oh KS, Kim M, Lee J, Kim MJ, Nam YS, Ham JE, Shin SS, Yoon M, Lee CM

Swim training for 6 weeks significantly decreased body weight gain, adipose tissue mass, and adipocyte size in both sexes of genetically obese db/db mice compared with their respective sedentary controls. Swim training also caused significant decreases in serum levels of free fatty acids, triglycerides, and total cholesterol in both sexes of obese mice. Concomitantly, hepatic mRNA levels of peroxisome proliferator-activated receptor alpha (PPARalpha) target enzymes responsible for mitochondrial and peroxisomal fatty acid beta-oxidation were significantly increased by swim training. Moreover, mRNA levels of uncoupling protein 2 (UCP2) in liver were also markedly increased by swim training. In conclusion, these results suggest that swim training-induced transcriptional activation of hepatic PPARalpha target enzymes and UCP2 may effectively prevent body weight gain, adiposity, and lipid disorders caused by leptin receptor deficiency in both sexes of mice.

Heart 2006 May 22; (Read article online)

McElduff P, Jaefarnezhad M, Durrington PN

Objective To compare national and international recommendations for statin treatment in the primary prevention of cardiovascular disease in middle aged men. Design Application of the current American, British and European recommendations to results of a prospective study. Participants Men aged 49-65 years (n=1653), who participated in the Caerphilly Prospective Study. Main outcome measures Proportion who would receive statin treatment, the number needed to treat (NNT) to prevent one first cardiovascular (CVD) event (myocardial infarction and stroke) over 10 years and the potential number of events prevented over 10 years in the whole population (population impact) by the use of statins in accordance with each set of guidelines, assuming a reduction of risk in the range 10-50% using the observed events and base-line risk factors. Results There were 212 events. For an anticipated reduction in first CVD events of 30% with statin treatment, the NNT was 26.0, if the whole population was treated. The lowest NNT was 12.1 for the National Health Service Framework (NSF), achieved when only 14% of the men received a statin. However, this prevented the lowest number of events (19.2/212) and had the smallest population impact on CVD incidence (-9.1%). The American and earlier Joint British Societies guidelines, although giving NNT's of around 21 prevented more events and had a greater population impact of -21.6 to - 23.3%. They did, however, target some 60% of the male population. The British Hypertension Society guidelines and new Joint British Societies recommendations achieved the greatest population impact of -27% whilst maintaining the NNT at 22.2. They did, however, target three quarters of this population. Conclusion Even effective preventive therapy will have little impact in preventing disease if its deployment does not include those at typical risk. Whether cholesterol-lowering on such a scale should be attempted with medication raises philosophical, psychological and economic considerations, particularly in view of the high likelihood of individual benefit from statin treatment. More effective nutritional policies to reduce serum cholesterol on a population level and reduce the requirement statins in primary prevention should also be considered.

Food Chem Toxicol 2006 Mar 30; (Read article online)

Tada Y, Fujitani T, Yano N, Takahashi H, Yuzawa K, Ando H, Kubo Y, Nagasawa A, Ogata A, Kamimura H

Tetrabromobisphenol A (TBBPA), brominated flame retardant, is produced in the largest amounts globally for use in plastics or building materials. TBBPA has been detected in sediment, air at the dismantling plant or human serum samples. In the present study, we examined the effects of prenatal and postnatal exposure to TBBPA in mice. TBBPA (99.1% pure) in diet was administered to pregnant ICR mice at doses of 0% (control), 0.01%, 0.1% or 1.0% from gestational day 0 to weaning at postnatal day 27. The average daily food intake and body weight of dams showed no significant differences between the control and treated groups. There were no dose-related effects on reproductive data. Serum concentrations of total-cholesterol and liver weights of treated dams and offspring were higher than those of the control mice. Histological findings in treated dams or offspring showed the increase of focal necrosis of hepatocytes and inflammatory cell infiltration in the liver, and increase of dilation or atrophy of renal tubules and cyst in the kidney. TBBPA was developed as a new, safe class of flame retardant and was not highly toxic. However, the present data suggested that TBBPA caused a lipid metabolic disorder and hepatic or kidney lesion, under these conditions.

Expert Rev Cardiovasc Ther 2006 May; 4(3): 345-351 (Read article online)

van der Graaf A, Hutten BA, Kastelein JJ, Vissers MN

Heterozygous familial hypercholesterolemia is associated with elevated low-density lipoprotein cholesterol levels and the development of premature cardiovascular disease. Despite this general statement, data regarding the incidence of cardiovascular disease in young women with familial hypercholesterolemia are lacking. In this review, information of age-specific incidence, risk factors and therapeutic avenues in women with heterozygous familial hypercholesterolemia are discussed.

Expert Rev Cardiovasc Ther 2006 May; 4(3): 283-91 (Read article online)

Armani A, Toth PP

Dyslipidemia is a highly heterogeneous group of disorders strongly influenced by both genetic and environmental factors. Dyslipidemia significantly increases risk for atherosclerotic disease and all of its various clinical manifestations. Identifying patients with dyslipidemia and initiating therapies aimed at normalizing the lipid profile has been demonstrated to significantly reduce the risk for myocardial infarction, stroke and cardiovascular mortality in both the primary and secondary prevention settings. Guidelines in Europe, Canada and the USA emphasize the need to reduce the burden of atherogenic lipoproteins in serum and to raise levels of high-density lipoproteins in patients at risk for cardiovascular events. Statins have emerged as front-line therapy for managing dyslipidemia, especially in patients with elevated serum levels of low-density lipoprotein cholesterol. As guidelines emphasize the need to reduce serum low-density lipoprotein cholesterol to lower levels, goal attainment can be challenging. The use of combination therapy increases the likelihood of therapeutic success for many patients. Furthermore, a significant percentage of patients with dyslipidemia either cannot achieve goals on statin monotherapy, choose not to take a statin or do not tolerate these drugs due to adverse side effects, such as myalgias, weakness or hepatotoxicity. This article summarizes the pharmacology, clinical efficacy and safety of colesevelam hydrochloride, a bile acid-binding resin. Bile acid-binding resins are orally administered anion-exchange resins that are not absorbed systemically. These agents bind bile acids and reduce their reabsorption at the level of the terminal ileum and prevent their enterohepatic recirculation. Colesevelam has a favorable side effect and toxicity profile and significantly impacts serum levels of lipoproteins when used as monotherapy or when used in combination with either statins or ezetimibe.

Mol Cell Biochem 2006 May 23; (Read article online)

Hack B, Witting PK, Rayner BS, Stocker R, Headrick JP

Despite the general understanding that ischemia-reperfusion (I/R) promotes oxidant stress, specific contributions of oxidant stress or damage to myocardial I/R injury remain poorly defined. Moreover, whether endogenous 'cardioprotectants' such as adenosine act via limiting this oxidant injury is unclear. Herein we characterized effects of 20 min ischemia and 45 min reperfusion on cardiovascular function, oxidative stress and damage in isolated perfused mouse hearts (with glucose or pyruvate as substrate), and examined whether 10 muM adenosine modified these processes. In glucose-perfused hearts post-ischemic contractile function was markedly impaired (< 50% of pre-ischemia), cell damage assessed by lactate dehydrogenase (LDH) release was increased (12 +/- 2 IU/g vs. 0.2 +/- 0.1 IU/g in normoxic hearts), endothelial-dependent dilation in response to ADP was impaired while endothelial-independent dilation in response to nitroprusside was unaltered. Myocardial oxidative stress increased significantly, based on decreased glutathione redox status ([GSSG]/[GSG + GSSH] = 7.8 +/- 0.3% vs. 1.3 +/- 0.1% in normoxic hearts). Tissue cholesterol, native cholesteryl esters (CE) and the lipid-soluble antioxidant alpha-tocopherol (alpha-TOH, the most biologically active form of vitamin E) were unaffected by I/R, whereas markers of primary lipid peroxidation (CE-derived lipid hydroperoxides and hydroxides; CE-O(O)H) increased significantly (14 +/- 2 vs. 2 +/- 1 pmol/mg in normoxic hearts). Myocardial alpha -tocopherylquinone (alpha-TQ; an oxidation product of alpha -TOH) also increased (10.3 +/- 1.0 vs. 1.7 +/- 0.2 pmol/mg in normoxic hearts). Adenosine treatment improved functional recovery and vascular function, and limited LDH efflux. These effects were associated with an anti-oxidant effect of adenosine, as judged by inhibition of I/R-mediated changes in glutathione redox status (by 60%), alpha-TQ (80%) and CE-O(O)H (100%). Provision of 10 mM pyruvate as sole substrate (to by-pass glycolysis) modestly reduced I/R injury and changes in glutathione redox status and alpha-TQ, but not CE-O(O)H. Adenosine exerted further protection and anti-oxidant actions in these hearts. Functional recoveries and LDH efflux correlated inversely with oxidative stress and alpha -TQ (but not CE-O(O)H) levels. Collectively, our data reveal selective oxidative events in post-ischemic murine hearts, which are effectively limited by adenosine (independent of substrate). Correlation of post-ischemic cardiovascular outcomes with specific oxidative events (glutathione redox state, alpha-TQ) supports an important anti-oxidant component to adenosinergic protection.

Life Sci 2006 Apr 29; (Read article online)

Savegnago L, Borges VC, Alves D, Jesse CR, Rocha JB, Nogueira CW

The aim of the present study was to evaluate pharmacological and toxicological properties of 1-buthyltelurenyl-2-methylthioheptene (compound 1). In vitro, compound 1 at 1 muM was effective in reducing lipid peroxidation induced by Fe/EDTA. Compound 1 presented neither thiol peroxidase nor thiol oxidase activity and did not change delta-ALA-D (delta-aminolevulinate dehydratase) activity (10-400 muM). Calculated LD(50) of compound 1, administered by oral route, was 65.1 mumol/kg. Rats treated with compound 1 did not reveal any motor impairment in the open field. Hepatic, renal and cerebral lipid peroxidation in treated rats did not differ from those in control rats. Conversely, 0.5 mumol/kg of compound 1 decreased lipid peroxidation in spleen. delta-ALA-D activity in liver and spleen was inhibited in rats treated with the higher dose of compound 1 but no significant differences were detected in renal delta-ALA-D activity. AST (aspartate aminotransferase) and ALT (alanine aminotransferase) activities as well as urea and creatinine levels were increased by high doses of compound 1 (50-75 mumol/kg). Compound 1 induced a significant decrease in plasma triglyceride levels but none of the doses tested changed the cholesterol level. This is a promising compound for more detailed pharmacological studies involving organotellurium compounds.

Heart 2006 May 22; (Read article online)

Ingelsson E, Arnlöv J, Lind L, Sundström J

OBJECTIVE: The relation of the metabolic syndrome to incident heart failure (HF) is unknown. Thus, our aim was to explore the metabolic syndrome as a possible risk factor for development of HF. DESIGN: Community-based cohort study. SETTING: Uppsala, Sweden. PARTICIPANTS: We enrolled 2314 50-year-old men free from HF, myocardial infarction and valvular disease at baseline between 1970 and 1974, and they were followed until the age of 70. We used a modified National Cholesterol Education Program (NCEP) definition of the metabolic syndrome with body mass index in the place of waist circumference. MAIN OUTCOME MEASURE: First hospitalisation for heart failure. RESULTS: In multivariable Cox proportional hazards models adjusted for established risk factors for HF (hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking and body mass index), the presence at baseline of the metabolic syndrome (hazard ratio, 1.66; 95% confidence interval, 1.02-2.70) was a predictor of subsequent HF. This relation was even stronger when adjusting for the presence of an acute myocardial infarction during follow-up in addition to the other established risk factors for CHF (hazard ratio 1.80, 95% confidence interval 1.11-2.91). CONCLUSION: The metabolic syndrome was a significant predictor of HF, independent of established risk factors for HF including an interim myocardial infarction, during two decades of follow-up in a community-based sample of middle-aged men. This implies that the metabolic syndrome provides important risk information beyond that carried by established risk factors for HF.

Mol Cell Biochem 2006 May 23; (Read article online)

Xi L, Ghosh S, Wang X, Das A, Anderson FP, Kukreja RC

Hypercholesterolemia (HCL) is commonly associated with impaired vascular relaxation response and augmented vasoconstriction. Interestingly, it was shown that animals with HCL were less vulnerable to seizures and several clinical studies also revealed a better outcome after stroke in the patients with HCL. To this context, the present study was designed to test the hypothesis that HCL would enhance the animals' resistance to severe systemic hypoxia and in turn prolong their survival time under such noxious condition. Four groups of middle-aged (mean age: 51.1 +/- 2.8 weeks) male C57BL/6J wild-type mice (C57BL-WT) and low-density lipoprotein receptor knockout mice (LDLR-KO) were included in the study: two groups were exposed to severe normobaric hypoxia (5% F(I)O(2)) and other two groups were used for brain tissue sample collection and Western blot analysis. The survival time under the hypoxic condition was recorded for each animal. Individual blood samples were collected immedtately after the cessation of spontaneous breathing for measuring plasma total cholesterol (TCL) and triglycerides. The results show that the hypoxia survival time was longer in LDLR-KO than C57BL-WT (i.e. 3.7 +/- 0.5 versus 2.3 +/- 0.2 min; P < 0.05). A positive correlation was found between TCL and the survival time (r (2) = 0.43; P < 0.05). Furthermore, a significant downregulation of vascular endothelial growth factor (VEGF) was observed in the brain tissue of LDLR-KO, as compared with C57BL-WT (n, = 3/group; P < 0.05), whereas expression of heme oxygenase 1 was similar in these two groups. We conclude that HCL enhances resistance to lethal systemic hypoxia (i.e. 61% increase in survival time) in middle-aged mice. This paradoxical protective effect of HCL was associated with a concomitant downregulation of cerebral VEGF expression, which could potentially blunt the hypoxia-triggered and VEGF-mediated pathophysiological events leading to death.

Horm Metab Res 2006 May; 38(5): 300-7 (Read article online)

Li Y, Fisher E, Klapper M, Boeing H, Pfeiffer A, Hampe J, Schreiber S, Burwinkel B, Schrezenmeir J, Döring F

Fatty acid-binding protein 2 (FABP2) is a cytosolic protein expressed exclusively in epithelial cells of the small intestine. Some, albeit not conclusive, evidence indicates that the Thr-allele of FABP2 Ala54Thr polymorphism is associated with type 2 diabetes. More recently, common FABP2 promoter polymorphisms have shown association with postprandial increase of triglycerides, body composition and plasma lipid levels. Therefore, we reasoned that variants in the FABP2 promoter may also predispose to type 2 diabetes mellitus. In our Caucasian study population, we found three SNPs and three insertion-deletion polymorphisms that are in complete linkage disequilibrium defining promoter haplotype A and B within 1kb 5' of the FABP2 initiation codon. Haplotype calculations indicated that the FABP2 promoter and Ala54Thr variants were strongly linked. Functional analysis of promoter fragments demonstrated that haplotype difference is caused by polymorphisms within 260 bp downstream of the FABP2 initiation codon. Using a prospective case-control study nested within the EPIC-Potsdam cohort of 192 incident type 2 diabetes cases and 384 sex-/age-matched controls, male subjects carrying the FABP2 haplotype B allele showed significantly decreased risk of type 2 diabetes when adjusted for BMI (OR = 0.50, 95 % CI = 0.28 - 0.87, p < 0.05) and additional covariates (OR = 0.42, 95 % CI 0.22 - 0.81, p < 0.01). Further adjustment for the Ala54Thr polymorphism revealed an OR of 0.18 (95 % CI 0.06 - 0.49, p < 0.001). Similarly, Ala/Ala homozygote males carrying the promoter haplotype B had decreased risk (0.33, 0.11 - 0.94, p < 0.05) of type 2 diabetes after stratification for the Ala54Thr polymorphism. FABP2 promoter haplotypes or genotype combinations defined by the promoter and Ala54Thr polymorphism were not associated with BMI, body fat, leptin, HbA (1c), total cholesterol or HDL. In conclusion, our findings suggest that the functional FABP2 promoter haplotype may contribute to type 2 diabetes in a sex-specific manner.

Atherosclerosis 2006 May 20; (Read article online)

Ishizaka N, Ishizaka Y, Toda EI, Hashimoto H, Nagai R, Yamakado M

Hyperuricemia is postulated to be a risk factor for atherosclerotic diseases, although whether it is independent of classical atherogenic risk factors is controversial. The automatic computer-assisted measurement of brachial-ankle pulse wave velocity (baPWV) is a valid and reproducible method by which to assess arterial stiffness, a potential surrogate marker of early atherosclerosis. By analyzing cross-sectional data from 982 individuals who underwent health screening, we have investigated whether serum uric acid is associated with high baPWV, which was determined as the highest quartile of baPWV values, in a sex-specific manner. Multivariate analysis showed that the odds ratios (95% CI) of the highest baPWV quartile across the sex-specific quartiles of serum uric acid were 1.0, 2.80 (0.93-8.40), 2.13 (0.74-6.19), and 2.76 (1.01-7.55) in women, and 1.0, 1.10 (0.55-2.20), 1.97 (1.04-3.75), and 2.24 (1.10-4.56) in men after adjusting for age, total and HDL-cholesterol, BMI, systolic blood pressure, triglycerides, fasting glucose and smoking status. The association between uric acid and high baPWV was observed in both subjects with metabolic syndrome and those without. These data suggest that in both genders, serum uric acid level is associated with increased baPWV, a marker of arterial stiffness, and is in part independent of other conventional risk factors for atherosclerosis and metabolic syndrome.

Undersea Hyperb Med 2006 Mar-Apr; 33(2): 95-101 (Read article online)

Kostopanagiotou G, Hamamoto I, Hartwell V, Nemoto EM

Nitrogen at high pressures and anesthetics increase lipid monolayer surface pressure and in turn modulates monolayer associated lipolytic enzyme activity that could alter membrane lipids. We tested the hypothesis that nitrogen at pressures of 5 and 10 megapascals (MPa) and pentobarbital induce alterations in synaptosomal membrane phospholipid and free fatty acid (FFA). Rat cortical synaptosomes in Krebs-Henseleit buffer were placed in steel chambers and incubated for four hours at 37 degrees C: at 5 or 10 MPa of O2/balance N2; at one 0.1 MPa on room air, and with 10 mg pentobarbital. Free fatty acids (FFA) were quantified by thin-layer and gas chromatography, and neutral and acidic lipids by high-pressure thin layer chromatography and protein by Biorad colorimetric assay. Statistical analyses were by ANOVA and posthoc analysis by Neuman-Keuls and Kruskal-Wallis tests at p < 0.05. Sphyngomyelin, phosphatidylcholine, phosphatidylethanolamine, cerebroside and cholesterol were unchanged by 5 and 10 MPa nitrogen and pentobarbital. Free fatty acids (16:00, 18:00, 18:01, 20:00, 22:0, 22:01 and 24:01) at 10 MPa were reduced compared to 5 MPa (p < 0.05) but unaffected by pentobarbital. The decrease in synaptosomal membrane FFA at 10 MPa suggests attenuated hydrolysis of membrane phospholipids without detectable alterations in membrane phospholipid composition.

Horm Metab Res 2006 May; 38(5): 336-40 (Read article online)

Heliövaara MK, Strandberg TE, Karonen SL, Ebeling P

BACKGROUND: Adiponectin is a recently discovered plasma protein with many associations to glucose and lipid metabolism. Due to its central role in cardiovascular diseases and insulin resistance, we studied the relationship between serum adiponectin and factors reflecting glucose and lipid metabolism. METHODS AND RESULTS: Thirty healthy participants (20M/10F, age 32.0 +/- 2.1 years, BMI 25.8 +/- 0.9 kg/m (2) and HbA (1c) 5.2 +/- 0.1 %) were studied four times at approximately one week intervals. The effects of a 4-hour euglycemic hyperinsulinemia (40 mU/m (2)/min), saline infusion (control), oral glucose, and oral fat load on serum adiponectin were studied. No significant correlation was found between serum adiponectin and insulin sensitivity before (r = 0.25) or after adjustment for age, BMI and gender (r = 0.04). Adiponectin concentration correlated inversely with HbA (1c) (r = - 0.43, p < 0.05), insulin concentration (r = - 0.38, p < 0.05) and triglyceride concentration (r = - 0.42, p < 0.05) but positively with HDL cholesterol (r = 0.38, p < 0.05). Metabolic procedures had no effect on serum adiponectin. CONCLUSIONS: Our findings favor the interpretation that adiponectin is not causally related to insulin sensitivity in healthy participants. The strongest associations of adiponectin in healthy participants are to be found to lipid metabolism. Serum levels of adiponectin are very stable and not acutely affected by hyperinsulinemia, oral glucose or fat load.

Biosci Biotechnol Biochem 2006 May; 70(5): 1134-9 (Read article online)

Inoue H, Kobayashi-Hattori K, Horiuchi Y, Oishi Y, Arai S, Takita T

We investigated the regulatory effects of structural differences among methylxanthine derivatives on the elevation of body fat percentage in developmental-stage rats. Caffeine, theophylline and theobromine were used as the methylxanthines. High-fat diets (20% lard) containing each methylxanthine (0.025%) were administered to male Sprague-Dawley rats for 12 weeks, with the result that the body fat percentage was generally reduced in each methylxanthine-fed group. The abdominal adipose tissue weight in the caffeine group was also significantly lower than that in the control group, the serum cholesterol and triglyceride levels in the caffeine group also being significantly lower than the levels in the control group. The study results suggest that caffeine could contribute most to preventing arteriosclerotic diseases.

Prog Neuropsychopharmacol Biol Psychiatry 2006 May 20; (Read article online)

Sarandol A, Sarandol E, Eker SS, Karaagac EU, Hizli BZ, Dirican M, Kirli S

Major depressive disorder (MDD) is blaimed to play a role in the onset of coronary artery disease (CAD). The aim of the present study was to investigate serum paraoxonase/arylesterase activities and oxidation of apolipoprotein B-containing lipoproteins in patients with MDD. Oxidation of lipoproteins plays an important role in atherogenesis and the enzyme paraoxonase, has been shown to prevent lipoprotein oxidation. Furthermore, low paraoxonase activity was suggested to predict CAD. Eighty-six patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for MDD and 36 healthy control subjects were included in the study. Serum paraoxonase and arylesterase activities were determined spectrophotometrically. Malondialdehyde (MDA) levels of apolipoprotein B-containing lipoproteins were determined before (basal) and after incubation with copper-sulphate, that yielded basal- and Delta-MDA values, respectively. Serum paraoxonase/arylesterase activities were significantly reduced in the post-treatment group compared with the pre-treatment group. Basal-MDA (MDA) level was significantly higher in the MDD group compared with the control group. Delta-MDA level of the severe MDD group was significantly higher than that of the control group. There was a positive correlation between the oxidizability of apolipoprotein B-containing lipoproteins and the severity of the disease. Total cholesterol, HDL-cholesterol, LDL-cholesterol, apolipoprotein B levels were significantly higher and apolipoprotein AI levels were significantly lower in the MDD group compared with those of the control group. The findings of the present study suggest that: 1) antidepressant treatment might reduce serum paraoxonase activity/mass; 2) oxidation and oxidizability of apolipoprotein B-containing lipoproteins seem to be increased in MDD.

Aesthetic Plast Surg 2006 May 22; (Read article online)

Hong YG, Kim HT, Seo SW, Chang CH, Rhee EJ, Lee WY

Recent advances in liposuction techniques now make it possible to remove considerable amounts of subcutaneous adipose tissue. However, the metabolic consequences of this procedure are not well documented. The aim of this study was to identify the effects from the surgical removal of subcutaneous fat on the body weights and serum lipids of patients who have undergone large-volume liposuction. In this study, eleven consecutive patients with a minimum aspirate volume of 5,000 ml were evaluated, and their serum lipids were measured at a postoperative 2-month follow-up assessment. Tumescent fluid was infiltrated using the superwet technique. The liposuction device used was a Liposlim(R) power-assisted liposuction system. The amount of solution infiltrated and the volume of aspirate were measured. Pre- and postoperative serum lipids, body weights, and body mass indices were compared. Statistical analysis was performed on lipid profile changes and aspirate volumes using Spearman's correlations. The average volumes of infiltrate and aspirate were 7,241 and 6,790 ml, respectively. Mean body weight decreased from 64.5 +/- 18.8 to 59.9 s +/- 17.8 kg (p < 0.01). The change in body weight per 1 l of aspirate volume was 0.67 +/- 0.10 kg/l. The mean body mass index dropped from 23.8 +/- 4.4 to 22.0 +/- 4.2 kg/m(2) (p < 0.01), and the mean total serum cholesterol levels from 168.2 +/- 23.6 to 162.9 +/- 26.5 mg/dl, an average of 3.2%. The mean low-density lipoprotein (LDL) decreased from 94.3 +/- 20.5 to 89.5 +/- 19.0 mg/dl, a 5.1% drop, and the mean high-density lipoprotein (HDL) decreased from 55.8 +/- 9.5 to 53.7 +/- 10.7 mg/dl, a 3,8% drop. The mean HDL/LDL proportion increased from 62.6 +/- 20.9% to 63.5 +/- 22.4%, averaging 1.4%. However, no significant correlation was found between the aspirated volume of fat and lipid profile change. In conclusion, over a 2-month period, large-volume liposuction reduced weight and total cholesterol level and increased the HDL/LDL ratio. The authors hope to discover whether the therapeutic impact of liposuction is long-lasting, and to determine whether it reduces the morbidity and mortality associated with obesity.

Biochem Biophys Res Commun 2006 May 12; (Read article online)

Krishna D, Le Doux JM

A number of viruses, when they bind to cells, activate intracellular signals that facilitate post-binding steps of infection. To determine if retroviruses activate intracellular signaling, we transduced HeLa cells with amphotropic retroviruses produced by TelCeB6 cells and examined cell lysates for activated Rac1. We found that retroviruses activate Rac1. Rac1 activation was blocked when cells were depleted of cholesterol, cultured in suspension, or incubated with an anti-beta(1) integrin antibody, and when viruses were treated with heparinase III. Retrovirus activation of Rac1 did not require the amphotropic envelope protein. Gene transfer was reduced 2.4-fold when viruses were treated with heparinase III, but did not change when cells were transduced in the presence of function-blocking anti-beta(1) integrin antibodies. The implications of these findings with respect to retrovirus-cell interactions are discussed.