Subcutaneous adipose tissue measurements and better metabolic prediction

The aim of the study was to establish the importance of an additional measurement of subcutaneous adipose tissue thickness (SAT) on a predetermined position on the waistline, and its relation to waist measurements as an improvement of metabolic prediction in equally obese subjects. One hundred and forty two consecutive patients were enrolled in the study: stratified by weight as normal (body mass index — BMI 20–25 kg/m²), overweight (BMI 25–30 kg/m²) and obese (BMI >30 kg/m²); and by fasting glucose level as normoglycemic, impaired fasting glucose (IFG), or with type 2 diabetes mellitus (T2DM). SAT was measured in relaxed expiration, 3 cm left of the umbilicus, with ultrasound. Fasting blood samples for glucose, insulin and HbAlc were taken. Waist circumference was slightly higher in the IFG (112.8 cm) and normoglycemic groups (115.62 cm), compared to T2DM (108.15 cm). The T2DM group had a lower average SAT (2.7 cm) than both the IFG group (3.4 cm, p<0.01) and the normoglycemic group (4.2cm, p=0.001). The homeostatic model of assessment for insulin resistance (HOMA IR) was the lowest in normoglycemic and the highest in IFG group. Waistline radius to SAT ratio provides better insight into the deterioration of glucose metabolism than standard anthropometric markers of abdominal obesity in equally obese patients.     

Effects of chronic ethanol consumption on levels of adipokines in visceral adipose tissues and sera of rats

Aim:

To investigate the effects of ethanol on adipokines (leptin, adiponectin, resistin, visfatin and cartonectin) levels in visceral adipose tissue (VAT) and sera, and explore the correlation between VAT and serum adipokine levels.

Methods:

Forty-eight Wistar rats were randomly divided into control, low, middle and high ethanol treatment groups that received 0, 0.5, 2.5, or 5.0 g of ethanol·kg^-1·d^-1, respectively, via gastric tubes for 22 weeks. The levels of fasting blood glucose (FBG) and fasting serum insulin (FINS) were measured and homeostasis model assessment of insulin resistance (HOMA-IR) values were calculated. Adipokines in perirenal and epididymal VAT and sera were measured by enzyme-linked immunosorbent assays (ELISAs).

Results:

High-dose treatments of ethanol (vs control group) significantly increased FINS (eg 37.86%) and HOMA-IR values (eg 40.63%). In VAT, levels of leptin, resistin and visfatin in the middle- and high-dose groups were significantly elevated, whereas adiponectin and cartonectin levels decreased. In sera, changes in adipokine levels were similar to that observed in VAT, with the exception of cartonectin. These ethanol-induced effects were dose-dependent. A positive correlation existed between VAT and serum adipokine levels, except for cartonectin.

Conclusion:

Chronic ethanol consumption affects adipokine levels in VAT and sera in a dose-dependent manner, with the exception of serum cartonectin. The altered levels of adipokines in VAT and sera are positively correlated.     

Sarsasapogenin improves adipose tissue inflammation and ameliorates insulin resistance in high-fat diet-fed C57BL/6J mice

Insulin resistance is a major cause of type 2 diabetes and metabolic syndrome.Macrophage infiltration into obese adipose tissue promotes inflammatory responses that contribute to the pathogenesis of insulin resistance.Suppression of adipose tissue inflammatory responses is postulated to increase insulin sensitivity in obese patients and animals.Sarsasapogenin(ZGY)is one of the metabolites of timosaponin AIII in the gut,which has been shown to exert anti-inflammatory action.In this study,we investigated the effects of ZGY treatment on obesity-induced insulin resistance in mice.We showed that pretreatment with ZGY(80 mg·kg^?1·d^?1,ig,for 18 days)significantly inhibited acute adipose tissue inflammatory responses in LPS-treated mice.In high-fat diet(HFD)-fed obese mice,oral administration of ZGY(80 mg·kg^?1·d^?1,for 6 weeks)ameliorated insulin resistance and alleviated inflammation in adipose tissues by reducing the infiltration of macrophages.Furthermore,we demonstrated that ZGY not only directly inhibited inflammatory responses in macrophages and adipocytes,but also interrupts the crosstalk between macrophages and adipocytes in vitro,improving adipocyte insulin resistance.The insulin-sensitizing and anti-inflammatory effects of ZGY may result from inactivation of the IKK/NF-κB and JNK inflammatory signaling pathways in adipocytes.Collectively,our findings suggest that ZGY ameliorates insulin resistance and alleviates the adipose inflammatory state in HFD mice,suggesting that ZGY may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.     

Different lipids remodeling signature demonstrated heterogeneity of white adipose tissue browning

OBJECTIVE White adipose tissue(WAT)browning confers beneficial effects on metabolic diseases.However, visceral adipose tissue(VAT) is not as susceptible to browning as subcutaneousadipose tissue(SAT).Therefore, interpreting the heterogeneity of VAT and SAT in brown remodeling is extremely important. METHODS We first investigated the effects of beta-3 adrenergic stimulation by CL316, 243 on systemic metabolism. Then, highcoverage targeted lipidomics approach with multiple reaction monitoring(MRM) was utilized to provide extensive detection of lipid metabolites in VAT and SAT using an Exion ultra performance liquid chromatography(UPLC)coupled with Sciex QTRAP 6500 Plus. RESULTS Beta-3 adrenergic stimulation notably ameliorated the systemic metabolism. Moreover, comprehensive lipidomics analysis elucidated different lipids adaptation between VAT and SAT in adrenergic-induced browning. CL316, 243 induced browning heterogeneity of VAT and SAT with more dramatic alteration of total lipid classes and individual molecular lipid species in VAT rather than SAT, though VAT is resistant to browning. Specifically, CL316, 243 stimulation differentially affected glycerides content in VAT and SAT and boosted the abundance of more glycerophospholipids species in VAT than in SAT. Besides, CL316,243 increased sphingolipids in VAT without changes in SAT, meanwhile, elevated cardiolipin species more prominently in VAT than in SAT. Further study uncovered that the lipids remodeling heterogeneity of VAT and SAT may attribute to a more significant alteration of lipids metabolism genes in VAT rather than SAT in response to CL316,243 treatment. CONCLUSION Our datasets provide acomprehensive analysis of lipids metabolic heterogeneity between VAT and SAT browning and may provide promising lipid targets to motivate WAT browning.     

The effects of ambient particulate matter on human adipose tissue

ABSTRACT

The effects of particulate matter (PM) air pollution on adipose tissue have mainly been studied in animal models. The aim of this study was to examine the potential associations between PM exposure and 25 cellular markers in human omental (OM) and subcutaneous (SC) adipose tissue. The PM exposure assessments for both PM_2.5 (PM <2.5 μm in diameter) and PM₁₀ (<10 μm) were based upon a novel hybrid satellite-based spatio-temporally resolved model. We calculated the PM exposure above the background threshold for 1 week (acute phase), 3 and 6 months (intermediate phase), and 1 year (chronic phase) prior to tissue harvesting and tested the associations with adipose cell metabolic effects using multiple linear regressions and heat maps strategy. Chemokine levels were found to increase after acute and intermediate exposure duration to PM₁₀. The levels of stress signaling biomarkers in the SC and OM tissues rose after acute exposure to PM₁₀ and PM_2.5. Macrophage and leucocyte counts were associated with severity of PM exposure in all three duration groups. Adipocyte diameter decreased in all exposure periods. Our results provide evidence for significant contribution of air pollutants exposure to adipose tissue inflammation as well as for pathophysiological mechanisms of metabolic dysregulation that may be involved in the observed responses.     

Differential effects of a gelatinase inhibitor on adipocyte differentiation and adipose tissue development

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Epicardial adipose tissue and atrial fibrillation: pathophysiological mechanisms,clinical implications,and potential therapies

Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with increased cardiovascular morbidity and mortality. Epicardial adipose tissue (EAT) serves as a biologically active organ with important endocrine and inflammatory function. Review An accumulating body of evidence suggests that EAT is associated with the initiation, perpetuation, and recurrence of AF, but the precise role of EAT in AF pathogenesis is not completely elucidated. Pathophysiological mechanisms involve adipocyte infiltration, profibrotic and pro-inflammatory paracrine effects, oxidative stress, neural mechanisms, and genetic factors.

Conclusions: Notably, EAT accumulation seems to be associated with stroke and adverse cardiovascular outcomes in AF. Weight loss, specific medications and ablation of ganglionated plexi (GP) seem to be potential therapies in this setting.     

Differential expression of miRNAs in the visceral adipose tissue of patients with non‐alcoholic fatty liver disease

Aliment Pharmacol Ther 2010; 32: 487–497

Summary

Background Progression of non‐alcoholic fatty liver disease (NAFLD) can be facilitated by soluble molecules secreted by visceral adipose tissue (VAT). MicroRNAs (miRNAs) are likely to regulate some of these molecular pathways involved in pathogenesis of NAFLD. Aim To profile miRNA expression in the visceral adipose tissue of patients with NAFLD. Methods Visceral adipose tissue samples were collected from NAFLD patients and frozen. Patients with biopsy‐proven NAFLD were divided into non‐alcoholic steatohepatitis (NASH) (n = 12) and non‐NASH (n = 12) cohorts controlled for clinical and demographic characteristics. Extracted total RNA was profiled using TaqMan Human MicroRNA arrays. Univariate Mann–Whitney comparisons and multivariate regression analysis were performed to compare miRNA profiles. Results A total of 113 miRNA differentially expressed between NASH patients and non‐NASH patients (P < 0.05). Of these, seven remained significant after multiple test correction (hsa‐miR‐132, hsa‐miR‐150, hsa‐miR‐433, hsa‐miR‐28‐3p, hsa‐miR‐511, hsa‐miR‐517a, hsa‐miR‐671). Predicted target genes for these miRNAs include insulin receptor pathway components (IGF1, IGFR13), cytokines (CCL3, IL6), ghrelin/obestatin gene, and inflammation‐related genes (NFKB1, RELB, FAS). In addition, two miRNA species, hsa‐miR‐197 and hsa‐miR‐99, were significantly associated with pericellular fibrosis in NASH patients (P < 0.05). Levels of IL‐6 in the serum negatively correlated with the expression levels of all seven miRNAs capable of down regulating IL‐6 encoding gene. Conclusions miRNA expression from VAT may contribute to the pathogenesis of NAFLD – a finding which may distinguish relatively simple steatosis from NASH. This could help identify potential targets for pharmacological treatment regimens and candidate biomarkers for NASH.     

Comparison of collagen content in skin wounds evaluated by biochemical assay and by computer-aided histomorphometric analysis

Context: The quantification of total collagen is of major importance in a wide range of research areas, including the study of cutaneous wound healing and new drugs trials.

Objective: The total collagen content in skin biopsies was compared by biochemical hydroxyproline assay and by two computer-aided histomorphometric analyses of histological sections.

Materials and methods: Two methods were used to evaluate collagen formation: the hydroxyproline assay, as the gold standard and histomorphometric image analysis of the filled areas by corresponding stained collagen fibres, using picrosirius and Gomori’s trichrome staining. The image analyses were determined by digital densitometry recognition using computer-aided ImageJ software. One-way ANOVA, simple linear regression and ANCOVA were applied for the statistical analysis and correlation.

Results: In a simple linear regression analysis carried out on the 14th day period after the induction of skin injury, three techniques, picrosirius red (F?=?33.57, p?=?0.00), Gomori’s trichrome (F?=?81.61, p?=?0.00) and hydroxyproline content (F?=?16.85, p?=?0.00) were able to detect collagen production. After scale adjustment, there were no significant differences among either the slopes (F?=?1.17, p?=?0.32) or the intercepts (F?=?0.69, p?=?0.51) of the estimated regression lines. It seems that a highly significant correlation exists between the histomorphometrical analysis and hydroxyproline assay.

Discussion and conclusion: The morphometric analysis proved to be adequate and can be used as a simple, rapid, low-cost technology for evaluating total collagen in cutaneous wound specimens, compared with the gold standard hydroxyproline assay.     

Deletion of adipose triglyceride lipase abolishes blood flow increase after β3-adrenergic stimulation in visceral adipose tissue of mice

Dynamic changes in adipose tissue blood flow (ATBF) with nutritional status play a role in the regulation of metabolic and endocrine functions. Activation of the sympathetic nervous system via β-adrenergic receptors (β-AR) contributes to the control of postprandial enhancement of ATBF. Herein, we sought to identify the role of each β-AR subtype in the regulation of ATBF in mice. We monitored the changes in visceral epididymal ATBF (VAT BF), induced by local infusion of dobutamine, salbutamol, and CL316,243 (a selective β1-, β2-, and β3-AR agonist, respectively) into VAT of lean CD-1 mice and global adipose triglyceride lipase (ATGL) knockout (KO) mice, using laser Doppler flowmetry. Administration of CL316,243, known to promote lipolysis in adipocytes, significantly increased VAT BF of CD-1 mice to a greater extent compared to that of the vehicle, whereas administration of dobutamine or salbutamol did not produce significant differences in VAT BF. The increase in VAT BF induced by β3-AR stimulation disappeared in ATGL KO mice as opposed to their wild-type (WT) littermates, implying a role of ATGL-mediated lipolysis in the regulation of VAT BF. Different vascular reactivities occurred despite no significant differences in vessel density and adiposity between the groups. Additionally, the expression levels of the angiogenesis-related genes were significantly higher in VAT of ATGL KO mice than in that of WT, implicating an association of ATBF responsiveness with angiogenic activity in VAT. Our findings suggest a potential role of β3-AR signaling in the regulation of VAT BF via ATGL-mediated lipolysis in mice.     

The role of microalbuminuria and insulin resistance as significant risk factors for white matter lesions in Japanese type 2 diabetic patients

ABSTRACT

Objective: The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. Microalbuminuria, which is associated with diabetes, has been flagged as a novel predictor for cerebrovascular events. This preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with microalbuminuria and insulin resistance in patients with type 2 diabetic mellitus (DM) not receiving insulin treatment.

Patients and methods: Based on brain magnetic resonance imaging (MRI) findings, 90 type 2 diabetic patients were divided into two groups: a WML-positive group (57?±?8 years, mean?±?SD, n?=?34) and a WML-negative group (57?±?6 years, n?=?56). The level of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin (F-IRI), homeostasis model assessment (HOMA) index, and hemoglobin A _1c (HbA1c).

Results: The body mass index was higher in the WML-positive group than in the WML-negative group (p?<?0.01). Plasma levels of triglycerides were higher while high-density lipoprotein cholesterol (HDL-C) was lower in the WML-positive group than in the WML-negative group (p?<?0.05 and p?<?0.0001, respectively). Fasting plasma glucose (p?<?0.005), insulin concentrations (p?<?0.0001), HOMA index (p?<?0.0001), and urinary albumin excretion (p?<?0.0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the microalbuminuria and insulin resistance (p?<?0.005, p?<?0.0005, respectively).

Conclusion: The results of this preliminary study indicate that the presence of WML was associated with the microalbuminuria and insulin resistance in these Japanese patients with type 2 DM; larger cohort studies are warranted to confirm these findings.     

Waist-hip ratio and low HDL predict the risk of coronary artery disease in Pakistanis

SUMMARY

Objective: To establish risk factor causal associations for coronary artery disease (CAD) in the native Pakistani population.

Methods: We conducted a hospital-based, case-control study of 200 cases with angiographically documented CAD and 200 age-and sex-matched controls without angiographic evidence of CAD. Patients on lipid lowering therapy were excluded. Lifestyle, anthropometric and biochemical risk factors were assessed in both groups.

Results: The presence of CAD was associated with current, past or passive smoking, a history of diabetes and high blood pressure, a positive family history of CAD, body fat percentage, waist-hip ratio (WHR), low apolipoprotein A1 or low HDL, lipoprotein (a), glucose, insulin, insulin resistance, C-reactive protein (CRP), total cholesterol to HDL ratio (TC/HDL) and creatinine on univariate conditional logistic regression analysis. In multiple regression analysis, significant independent

associations were found with low HDL (OR 0.11; 95% CI 0.04–0.34; p?<?0.001) positive family history (OR 1.79; 95% CI 1.09-2.93; p?=?0.02), CRP (OR 1.45; 95% CI 1.19–1.75; p?<?0.001) and WHR (OR 1.04; 95% CI 1.01-1.08; p?=?0.01). Angiograms were also quantified for the extent and severity of CAD by the Gensini scoring system. Quantitative angiographic data showed associations with age (p?=?0.01), the duration of diabetes (p?=?0.04), WHR (p?=?0.06), low HDL (p?<?0.001), lipoprotein (a) (p?=?0.001), creatinine (p?<?0.001) and CRP (p?=?0.007). Results indicate that total and LDL cholesterol were not significant risk factors in this study; levels were below currently accepted thresholds for treatment.

Conclusions: The cardiovascular risk profile in this population is consistent with metabolic syndrome where low HDL and WHR can be used to predict the risk of CAD. Results suggest the need to redefine the currently practised approach to CAD management in this population to fit local needs.     

Antiretroviral concentrations and surrogate measures of efficacy in the brain tissue and CSF of preclinical species

Abstract

1. Antiretroviral concentrations in cerebrospinal fluid (CSF) are used as surrogate for brain tissue, although sparse data support this. We quantified antiretrovirals in brain tissue across preclinical models, compared them to CSF, and calculated 90% inhibitory quotients (IQ₉₀) for nonhuman primate (NHP) brain tissue. Spatial distribution of efavirenz was performed by mass-spectrometry imaging (MSI).

2. HIV or RT-SHIV-infected and uninfected animals from two humanized mouse models (hemopoietic-stem cell/RAG2-, n?=?36; bone marrow-liver-thymus/BLT, n?=13) and an NHP model (rhesus macaque, n?=18) were dosed with six antiretrovirals. Brain tissue, CSF (NHPs), and plasma were collected at necropsy. Drug concentrations were measured by LC-MS/MS. Rapid equilibrium dialysis determined protein binding in NHP brain.

3. Brain tissue penetration of most antiretrovirals were >10-fold lower (p?<?0.02) in humanized mice than NHPs. NHP CSF concentrations were >13-fold lower (p?<0.02) than brain tissue with poor agreement except for efavirenz (r?=?0.91, p?=?0.001). Despite 97% brain tissue protein binding, efavirenz achieved IQ₉₀>1 in all animals and 2-fold greater white versus gray matter concentration.

4. Brain tissue penetration varied across animal models for all antiretrovirals except raltegravir, and extrapolating brain tissue concentrations between models should be avoided. With the exception of efavirenz, CSF is not a surrogate for brain tissue concentrations.     

Modeling the oral glucose tolerance test in normal and impaired glucose tolerant states: a population approach

Objective: The conventional approach to analyzing data from oral glucose tolerance testing (OGTT) requires model identification in each individual separately (standard two stage, STS), ignoring knowledge about the population as a whole. In practice, however, the OGTT is sparsely sampled and individual estimates are often not resolvable from available data. This weakness is often encountered in large scale trials or epidemiological studies, leading to either multiple imputations or simply much less data available for analysis.

Methods: We have applied a population approach, nonlinear mixed effects modeling, to plasma glucose, insulin and C-peptide data obtained from a 120?minute OGTT undertaken by 106 subjects with varying glucose tolerance. This method provides estimates of population means, variances and covariances of model parameters and empirical Bayes estimates of individual parameter values, as well as measures of intra-individual (within-subject) and inter-individual (between-subject) variability. The recently developed oral glucose minimal model was used to evaluate insulin sensitivity, and a combined model approach was used to assess β-cell secretion.

Results: Applying these models allowed for the reconstruction of insulin secretion and glucose absorption profiles and gave population indexes of insulin sensitivity (S_I?=?6.51?±?1.20?×?10^?4 min^?1·μU^?1·ml), fractional hepatic extraction of insulin (F?=?0.522?±?0.291) and fractional insulin clearance (k_I?=?0.258?±?0.151?min^?1). Whereas the traditional approach to parameter estimation failed to recover estimates in more than one third of the population, the population approach provided individual estimates in all subjects. Examination of the empirical Bayes estimates showed that individual parameter estimates were able to differentiate well between individuals at glucose tolerant states ranging from euglycemia to overt type 2 diabetes.

Conclusions: Our findings suggest that population analysis is a powerful tool for obtaining accurate assessments of indexes of insulin sensitivity and β-cell function from the OGTT, especially in epidemiological studies with large numbers of sparsely sampled subjects.     

The association of smokeless tobacco use and pack-years of smokeless tobacco with age-related macular degeneration in Indian population

Aim: To explore the association of use versus no use and the influence of pack-year use of smokeless tobacco with that of early and late age-related macular degeneration (AMD) in rural and urban south Indian population. We hypothesized that the use and pack-years of use would be significantly associated with both early and late AMD. We therefore sought to examine subjects who gave a history of using smokeless tobacco and we quantified the usage as pack-years, to examine the association with that of early and late AMD.

Materials and methods: This was part of Sankara Nethralaya: Rural–Urban Age-related Macular degeneration study (SN-RAM study), which was conducted between 2007 and 2010. Subjects aged 60 years or older or those turning 60 in the present calendar year, with a history of using smokeless tobacco were noted along with duration and number of packs used per day. Smokeless tobacco was defined as chewed-tobacco (loose leaves) and/or snuff (finely chopped tobacco). Subjects underwent detailed ophthalmic evaluation including cataract grading using the Lens Opacities Classification System (LOCS III), 45° 4-field stereoscopic fundus photography and AMD evaluation. Pack-years of smokeless tobacco use was stratified as <15, 15–34 and ≥35 years; the association of tobacco use and pack-years of use with that of early and late AMD was examined. A p value of Results: The number of smokeless tobacco users was significantly higher in rural (n?=?767) than in urban groups (n?=?281), p?p?=?0.756 or that between AMD and no AMD, p?=?0.562. Use of smokeless tobacco compared with no use was significantly associated with late AMD, OR=?3.178, 95%CI: 1.095, 9.227, p?=?0.033, when adjusted for age, gender, rural-urban differences, presence of diabetes, socioeconomic status, systolic and diastolic blood pressure, total cholesterol, low-density and high-density lipoprotein levels. The association was not significant for early AMD, p?=?0.582. The pack-years of use did not show a statistically significant association with early or late AMD. Furthermore, out of the 1048 subjects, 547 reported as using areca nut. Of which, 415 (75.8%) subjects had no AMD, 119 (21.7%) showed evidence of early AMD and 13 (2.4%) had late AMD. There was no significant association between the use of areca nut and early AMD, (X² (1, N?=?930)?=?2.345, p?=?0.126) or with that of late AMD (X² (1, N?=?761)?=?0.075, p?=?0.785).

Conclusions: Smokeless tobacco use compared with no use, is associated with late AMD, regardless of the pack-years of use. Tobacco use is a modifiable risk factor. Efforts to reduce or stop the use of smokeless tobacco is indicated in an effort to prevent vision loss with respect to late AMD.     

Identity talk on dangerous consumptions down-under

Abstract

Aim: To explore participation with alcohol marketing (i.e. commenting on brand statuses) and user-created promotion on social media (i.e. photos of peers drinking) by young people in the United Kingdom (UK), and what association this has with higher-risk consumption and brand identification.

Method: Online cross-sectional survey with 11–19-year olds in the UK (n?=?3,399) (average age: 15?years old). Past-month participation was measured for five forms of alcohol marketing on social media and one form of user-created promotion (all Yes/No). Past-month awareness of nine wider alcohol marketing activities, social media apps used at least weekly, and ownership of branded merchandise were included as covariates. Outcomes included higher-risk consumption in current drinkers (≥5 AUDIT-C) and brand identification in all respondents (8 pictures with brand names removed).

Results: Over one-in-ten respondents (13.2%) had participated with at least one form of marketing on social media or participated with user-created promotion (12.2%). For both, participation was greater in current drinkers and those of legal purchasing age. A logistic regression found that participation with two or more forms of marketing on social media (AOR?=?1.96, p?AOR?=?3.46, p?SD?=?2.12) alcohol brands. A linear regression found participation with marketing on social media was not associated with brand identification (β?=?0.01, p?=?.42) but participation with user-created promotion was (β?=?0.05, p?Conclusion: Social media provides opportunities for adolescents to participate with commercial marketing and user-created promotion and this is associated with higher-risk consumption and brand identification.     

Serum paraoxonase activity and oxidative status in subjects with alopecia areata

Abstract

Introduction: Previous studies have suggested that oxidative stress may play an important role in the pathogenesis of alopecia areata (AA) but these reports are limited and conflicting.

Objectives: The aim of this study was to investigate serum paraoxonase-1 (PON1) activity and oxidative status in subjects with AA.

Materials and methods: Thirty-nine subjects with AA and 39 healthy controls were enrolled. Serum PON1 activity, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined.

Results: Serum TAC levels and PON1 activity were significantly lower in the subjects with AA than controls (p?=?0.038, p?=?0.001, respectively), whereas TOS levels and OSI were significantly higher (both, p?=?0.001) in the subjects with AA.

Conclusions: Our results suggest that reduced PON1 activity may be related to increased oxidant and decreased antioxidant levels. These data indicated that oxidant/antioxidant imbalance may play a role in the etiopathogenesis of AA.     

Dose-dependent effects of chronic ethanol on mouse adipose tissue lipase activity and cyclic AMP accumulation

1. The effects of two chronic ethanol treatment schedules, which produce different plasma ethanol concentrations, on the specific activities of adipose tissue lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) have been investigated in brown and white fat.
2. Mice provided with 20% ethanol solution as sole drinking fluid for 28 days consumed between 13 and 15 g ethanol kg⁻¹ body weight day⁻¹ over days 22–28. The mean plasma ethanol concentration was 4.94±1.4 mM (n=8) at 09 h 00 min on day 28 when the lipase assays were performed. Mice given ethanol in a liquid diet for 7 days consumed between 15 and 18 g ethanol day⁻¹ over days 3–7. The mean plasma ethanol concentration was 15.9±4.7 mM (n=8) at 09 h 00 min on day 7. These concentrations of ethanol had no effect on the activity of either LPL or HSL in vitro.
3. LPL activity in white and brown fat (expressed as nmol fatty acids released h⁻¹ mg⁻¹ acetone powder) was unaltered 60 min following an acute injection of ethanol (2.5 g kg⁻¹, i.p.) which produced a mean blood ethanol level of 37.5±6.7 mM. HSL activity in white fat (expressed as nmol fatty acid released h⁻¹ mg⁻¹ protein) was also unaffected by this acute dose of ethanol, but the activity in brown fat was significantly reduced: 3.07±0.30 (n=8) after ethanol compared to 4.36±0.25 (n=12) in controls (P<0.01).
4. LPL activity in white fat was little altered by either of the chronic ethanol treatment schedules whilst LPL activity in the brown fat from the same animals was significantly increased compared to the respective control values: 0.27±0.03 (ethanol drinking), control: 0.16±0.01; 0.79±0.14 (ethanol liquid diet), control: 0.39±0.05.
5. HSL activity in white fat was significantly increased by the chronic drinking treatment (7.7±0.5; control: 3.78±0.17, n=8) at the same time that the activity in brown fat was reduced (3.76±0.2; control: 4.74±0.16). The ethanol liquid diet also reduced HSL activity in brown fat but had negligible effect in white fat.
6. The effects of the two chronic ethanol treatments on adenosine 3′ : 5′-cyclic monophosphate (cyclic AMP) accumulation in brown and white fat were very similar, both qualitatively and quantitatively, to the effects on HSL.
7. It has been shown that brown and white adipose tissues respond differently to the presence of chronic ethanol and that the response is dependent both upon the concentration of ethanol and the nature of the diet with which the ethanol is administered. The effects of ethanol on adipose tissue HSL activity appear to be mediated via changes in the tissue cyclic AMP level and, in this respect, brown fat is more sensitive to ethanol than white fat.

     

24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain

ABSTRACT

Background: Collagen hydrolysate is a nutritional supplement that has been shown to exert an anabolic effect on cartilage tissue. Its administration appears beneficial in patients with osteoarthritis.

Objective: To investigate the effect of collagen hydrolysate on activity-related joint pain in athletes who are physically active and have no evidence of joint disease.

Design and setting: A prospective, randomized, placebo-controlled, double-blind study was conducted at Penn State University in University Park, Pennsylvania. Parameters including joint pain, mobility, and inflammation were evaluated with the use of a visual analogue scale during a 24-week study phase.

Study participants: Between September 2005 and June 2006, 147 subjects who competed on a varsity team or a club sport were recruited. Data from 97 of 147 subjects could be statistically evaluated.

Intervention: One hundred and forty-seven subjects (72 male, 75 female) were randomly assigned to two groups: a group (n?=?73) receiving 25?mL of a liquid formulation that contained 10?g of collagen hydrolysate (CH-Alpha)^* and a group (n?=?74) receiving a placebo, which consisted of 25?mL of liquid that contained xanthan.

Main outcome measures: The primary efficacy parameter was the change in the visual analogue scales from baseline during the study phase in relation to the parameters referring to pain, mobility, and inflammation.

Results: When data from all subjects (n?=?97) were evaluated, six parameters showed statistically significant changes with the dietary supplement collagen hydrolysate (CH) compared with placebo: joint pain at rest, assessed by the physician (CH vs. placebo (–1.37?±?1.78 vs. –0.90?±?1.74 (?p?=?0.025)) and five parameters assessed by study participants: joint pain when walking (–1.11?±?1.98 vs. –0.46?±?1.63, p?=?0.007), joint pain when standing (–0.97?±?1.92 vs. –0.43?±?1.74, p?=?0.011), joint pain at rest (–0.81?±?1.77 vs. –0.39?±?1.56, p?=?0.039), joint pain when carrying objects (–1.45?±?2.11 vs. –0.83?±?1.71, p?=?0.014) and joint pain when lifting (–1.79?±?2.11 vs. –1.26?±?2.09, p?=?0.018). When a subgroup analysis of subjects with knee arthralgia (n?=?63) was performed, the difference between the effect of collagen hydrolysate vs. placebo was more pronounced. The parameter joint pain at rest, assessed by the physician, had a statistical significance level of p?=?0.001 (–1.67?±?1.89 vs. –0.86?±?1.77), while the other five parameters based on the participants’ assessments were also statistically significant: joint pain when walking (?p?=?0.003 (– 1.38?±?2.12 vs. – 0.54?±?1.65)), joint pain when standing (?p?=?0.015 (–1.17?±?2.06 vs. –0.50?±?1.68)), joint pain at rest with (?p?=?0.021 (–1.01 ±1.92 vs. –0.47?±?1.63)), joint pain when running a straight line (?p?=?0.027 (–1.50?±?1.97 vs. –0.80?±?1.66)) and joint pain when changing direction (?p?=?0.026 (–1.87?±?2.18 vs. –1.20?±?2.10)).

Conclusion: This was the first clinical trial of 24-weeks duration to show improvement of joint pain in athletes who were treated with the dietary supplement collagen hydrolysate. The results of this study have implications for the use of collagen hydrolysate to support joint health and possibly reduce the risk of joint deterioration in a high-risk group. Despite the study's size and limitations, the results suggest that athletes consuming collagen hydrolysate can reduce parameters (such as pain) that have a negative impact on athletic performance. Future studies are needed to support these findings.     

Cigarette Smoking is Independently Associated with Markers of Endothelial Dysfunction and Hyperinsulinaemia in Non-diabetic Individuals with Coronary Artery Disease

SUMMARY

Background: Oxidative stress and endothelial dysfunction have been introduced as a unifying pathological mechanism for early atherosclerotic disease. They are caused by a variety of stimuli including cigarette smoking (environmental) and type 2 diabetes (disease factor). However, the role of hyperinsulininaemia, a marker of insulin resistance, as a risk factor for atherosclerosis remains to be clarified.

Study objectives: To study the relationship of smoking, hyperinsulinaemia and biochemical markers of oxidative stress and endothelial dysfunction, in patients with coronary artery disease.

Design: Case-control study of 5-year survivor status in smokers, former smokers and non-smokers with angiographically documented stable coronary artery disease classified by self-reporting of smoking status together with plasma cotinine measurements.

Setting: Cardiology and cardiac surgery unit of a tertiary care referral centre.

Patients and methods: Plasma levels of vitamins C, E and selenium, and the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were assessed in 214 patients at baseline together with the glucose and insulin response to an oral glucose challenge. Sixty known or newly diagnosed type 2 diabetic patients (28%) were identified and excluded from further analysis.

Results: E-selectin and ICAM-1, serving as markers of endothelial dysfunction, significantly correlated with hyperinsulinaemia (p?<?0.05). Circulating immunoreactive insulin was elevated in active smokers and former smokers as compared to non-smokers after an oral glucose load (p?<?0.05 for the area under the insulin time curve), despite a similar glucose response. Smoking was associated with a decrease in antioxidant vitamins C (p?=?0.02) and E (p?=?0.03), and an increase of E-selectin (p?<?0.05) and ICAM-1 (p?<?0.001). Low baseline ICAM-1 and high vitamin C levels emerged as the most significant multivariate predictors of 5-year survival (p?<?0.001).

Conclusions: Hyperinsulinaemia in smokers is linked with markers of endothelial dysfunction. Impaired vascular reactivity can thus be a new possible mechanism linking insulin resistance and smoking.