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Background: Chronic systemic low-grade inflammation is a key feature of obesity because of adipose tissue inflam-mation with overexpressed pro-inflammatory cytokines. Magnesium (Mg) deficiency is one of the pathophysiological links between inflammation and obesity. Detection of factors contributing to obesity are therefore fundamental strategy in obesity management. Aim of Study: To determine the relationship between the serum level of Mg, dietary intake of Mg and inflammation among a sample of Medical Ain Shams students. Subjects and Methods: The current study is a descriptive study of 60 medical students divided into two equal groups. Group 1 includes normal weight students with BMI between 18.5-24.9kg/m2 and group 2 includes obese students with BMI >!30kg/m2. Results: There was a significant increase in BMI, Waist Circumference (WC), Waist Hip Ratio (WHR), C-Reactive Protein (CRP), and decrease in serum Mg and dietary intake of Mg in the obese group compared to normal weight group. Moreover, BMI, WC, and WHR were positively correlated with CRP and negatively correlated with serum Mg. Serum Mg and dietary intake of Mg were negatively correlated with CRP. Conclusion: Our study may lend an additional support to the positive relationship between obesity and inflammatory status. Also, it confirms the negative relationship between obesity/inflammatory stress to Mg status in this subset of obese students as compared to normal weight students in Faculty of Medicine, Ain Shams University.

Background: Overweight and obesity occur when excess fat accumulation increases risk to health, leading to expression of co-morbid diseases occur at different thresholds. That's why obesity is now recognized as a chronic or non-communicable disease. Aim of Study: To assess serum uric acid and diet contrib-uting in its increased concentration level in relation to inflam-mation in a subsample of obese medical students as compared to normal-weight medical students in Faculty of Medicine Ain Shams University. Subjects and Methods: The current study is a case control study of 63 students among 1220 Ain Shams medical students. Our study group was divided into two groups. Group 1 included 30 students with BMI between 18.5-24.9Kg/m2. Group 2 included 33 students with BMI >!30Kg/m2. Results: There was significant difference between the two groups in weight, waist circumference and waist hip ratio, but not for height. As regards CRP serum level, the obese group showed significant increase in serum level. In the same time there was a significant positive correlation between the CRP serum level and BMI, WC and WHR in both groups. On the other hand, protein intake was significantly higher in obese group than normal weight group, as a part of increased caloric intake. When comparing serum uric acid level in the two groups there was a statistically significant difference, and on searching for a relation between the serum uric acid and BMI, WC, CRP and protein intake serum level, a positive correlation was found. Conclusion: Serum UA level is a crucial biomarker, it could induce inflammation and hence increases adiposity or its increase results from increased obesity. Moreover, increased serum uric acid is correlated to increased protein intake in obese individuals with increased total caloric intake specially protein content.

Effective interventions and treatments for complex diseases have been implemented globally, however, coverage in Africa has been comparatively lower due to lack of capacity, clinical applicability and knowledge on the genetic contribution to disease and treatment. Currently, there is a scarcity of genetic data on African populations, which have enormous genetic diversity. Pharmacogenomics studies have the potential to revolutionise treatment of diseases, therefore, African populations are likely to benefit from these approaches to identify likely responders, reduce adverse side effects and optimise drug dosing. This review discusses clinical pharmacogenetics studies conducted in African populations, focusing on studies that examined drug response in complex diseases relevant to healthcare. Several pharmacogenetics associations have emerged from African studies, as have gaps in knowledge.

Gut microbiota-derived short-chain fatty acids (SCFAs) have been reported to result in a wide range of health benefits including improvements in body composition and reduced body weight. However, excess production of colonic SCFAs has been implicated in the promotion of obesity. In this study, we aimed to explore the interrelation between diet, SCFAs production and obesity. This study included 31 subjects divided into a lean group and an obese group. Their dietary habits were assessed by means of food-frequency questionnaire and 24-hour recall then blood samples were collected from all of them. Analysis of short-chain fatty acids (i.e., acetate, propionate, and butyrate) in serum was performed using gas chromatography-mass spectrometry (GC-MS). Dietary assessment revealed that obese subjects had a significantly higher intake of carbohydrate, fat and sodium while lean subjects had a significantly higher intake of dietary fiber. Serum levels of propionate were higher in lean subjects compared to obese subjects (P

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-κB inhibitor (SN50) effect on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-κB activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-κB inhibitor, SN50 (50μg/ml). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50μg/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-κB p65 and AGT. Gene expression of TNF-α and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-κB p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight (P=

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise because of the pathogenic inflammatory nature of the abdominal fat depot. Pro-inflammatory cytokine and adipokine upregulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered to have an important function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the effect of an NF-κB inhibitor (SN50) on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its effects on NF-κB activity in human adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight subjects and 10 obese subjects with and without hypertension and treated with 10 ng/mL of lipopolysaccharides (LPS) in the presence and absence of NF-κB inhibitor SN50 (50 μg/mL). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10 ng/mL) and SN50 (50 μg/mL) using commercially available assays. The NF-κB p65 protein and AGT were detected by the western blot technique. Gene expression of TNF-α and AGT were detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of abdominal subcutaneous (AbdSc) adipocytes with LPS (10 ng/mL) caused a significant increase in NF-κB p65 in overweight subjects and obese subjects with and without hypertension (p = 0.001) at 24 h of incubation, whereas, SN50-NF-κB inhibitor caused a reduction in NF-κB p65 in overweight subjects (p < 0.001) and obese subjects with and without hypertension (p = 0.001) at 24 h of incubation. Treatment of AbdSc adipocytes with 10 ng/mL LPS caused a significant increase in TNF-α secretion in overweight subjects and obese subjects at all time points (p < 0.001), whereas SN50 led to a decrease in TNF-α secretion at 3 and 12 h of incubation. Treatment of AbdSc adipocytes with LPS (10 ng/mL) caused a twofold increase in TNF-α and AGT gene expression compared with untreated cells, whereas, in the presence of SN50, it reduced mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent important biomarkers to evaluate hypertension risk and may provide insight into the pathogenesis of obesity-related hypertension.

With the introduction of integrated approach in the medical curriculum, there is a need to teach basic sciences in a way relevant to real clinical scenarios. The aim of this study is to investigate the feasibility of case-based learning (CBL) for teaching of medical biochemistry to a large number of medical students. It also evaluates both the students’ and faculty members’ perception of this approach. CBL was introduced in teaching medical biochemistry in the Neuroscience block for the second-year medical students. This study’s students were from two consecutive academic years (n = 721 and 769). Four clinical cases were prepared. Students were divided into subgroups, each having one CBL session every 2 weeks. Students were encouraged to work together to understand the given clinical scenario by building on past knowledge obtained through other teaching modalities and new knowledge acquired during the session. A pretest was administered at the beginning of the session, and an identical posttest administered at the end of the session. Perception of both the students and facilitators of the CBL-teaching approach was evaluated using end-of-block questionnaires. In both studied academic years, students got higher scores in posttest compared to pretest scores with a statistically significant difference of the paired scores (P

Objective: To assist healthcare providers in evidence-based clinical decision-making for the management of overweight and obese adults in Saudi Arabia. Methods: The Ministry of Health, Riyadh, Kingdom of Saudi Arabia assembled an expert Saudi panel to produce this clinical practice guideline in 2015. In collaboration with the methodological working group from McMaster University, Hamilton, Canada, using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, which describes both the strength of recommendation and the quality of evidence Results: After identifying 11 questions, corresponding recommendations were agreed upon as guidance for the management of overweight and obese adults. These included strong recommendations in support of lifestyle interventions rather than usual care alone, individualized counseling interventions rather than generic educational pamphlets, physical activity rather than no physical activity, and physical activity in addition to diet rather than diet alone. Metformin and orlistat were suggested as conditional recommendations for the management of overweight and obesity in adults. Bariatric surgery was recommended, conditionally, for the management of obese adults (body mass index of ≥40 or ≥35 kg/m 2 with comorbidities). Conclusions: The current guideline includes recommendation for the non-pharmacological, pharmacological, and surgical management of overweight and obese adults. In addition, the panel recommends conducting research priorities regarding lifestyle interventions and economic analysis of drug therapy within the Saudi context, as well as long term benefits and harms of bariatric surgery. Saudi Med J 2016; Vol. 37 (10): 1151-1162 doi: 10.15537/smj.2016.10.14353 How to cite this article: Alfadda AA, Al-Dhwayan MM, Alharbi AA, Al Khudhair BK, Al Nozha OM, Al-Qahtani NM, Alzahrani SH, Bardisi WM, Sallam RM, Riva JJ, Brozek JL, Schunemann HJ, Moore A. The Saudi clinical practice guideline for the management of overweight and obesity in adults. Saudi Med J . 2016 Oct;37(10):1151-62. doi: 10.15537/smj.2016.10.14353.

Indoleamine 2,3-dioxygenase (IDO), a catabolizing enzyme of tryptophan, is a novel immunosuppressive agent blocking T-cell activation in neoplastic cells, including acute myeloid leukemia (AML) cells. IDO inhibitors as 1-methyl tryptophan (1MT) can abrogate IDO enzymatic activity and may result in an effective immune response. Mononuclear cells (MNCs) were separated from peripheral blood of 25 AML patients and 25 normal adults. IDO expression was detected by RT-PCR and its enzymatic activity by a colorimetric method. MNCs were cultured and the effects of Adriamycin, 1MT and a mixture of both on blast and lymphocyte cell counts after 24 and 72 h were detected. IDO mRNA and activity were detected in 52% of patients and absent in normal subjects. There was a significant correlation between IDO mRNA expression and its enzymatic activity in AML. IDO activity was correlated positively with patient's ages and negatively with hemoglobin levels. There was a significant inhibition of blast cells proliferation with Adriamycin and more inhibition when combined with 1MT. The inhibition was more after 72 h more than 24 h of culture. However, using 1MT alone showed no significant inhibitory effect on blast cells, with a significant increase in lymphocyte counts. Our study confirms the role of indoleamine 2,3-dioxygenase in tumor-induced immune tolerance and points to the possible benefit of 1-methyl tryptophan as immunotherapeutic enhancing the anticancer effects of traditional chemotherapeutics.

Objective—Preeclampsia has been associated with elevated pro-inflammatory markers, increased sympathetic activity and decreased plasma volume. We hypothesized that these associations would be identified in women prior to a first pregnancy. Methods—We studied 76 healthy nulligravid subjects measuring the pro-inflammatory markers Creactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha. Plasma volume (PV) was measured in supine position and corrected for body mass index (BMI). We examined supine plasma levels of epinephrine and norepinephrine and blood pressure response to Valsalva’s maneuver to quantify sympathetic activation. We then examined the association of plasma volume and sympathetic activity with pro-inflammatory cytokines with P < 0.05 accepted for significance. Results—CRP was significantly increased in subjects with lowest PV/BMI quartile when compared to middle two quartiles and highest quartile (ANOVA, p = 0.037). We found no significant association of PV/BMI with either interleukin 6 or tumor necrosis factor alpha. Both plasma epinephrine concentration (r = 0.29, P = 0.02) and the phase II_L blood pressure response to Valsalva’s maneuver (r = 0.44, P < 0.0001) were associated with serum IL-6 concentrations. Conclusions—Low plasma volume is associated with increased CRP levels and increased sympathetic tone is linked to elevated IL-6 concentration in young non-pregnant women. These findings represent elements of a non-pregnancy phenotype that parallels the findings observed in preeclampsia and in women at risk for ischemic cardiovascular disease. This suggests that the relationships observed during preeclampsia, which have been associated with placental pathology, may predate pregnancy and be independent of placental activity.

Objective This study aims to explore the baseline adipocytokine profiles of adult Saudis and evaluate their relationship in the development of insulin resistance. Methods In this cross-sectional study, 300 adult Saudis with varying glucose tolerance were recruited. They were grouped into NGT, IGT and DM. Anthropometrics, glucose and lipid profiles were analyzed by routine methods; leptin, adiponectin, resistin and CRP were measured by ELISA. Results Insulin resistance was significantly correlated with levels of CRP ( R = 0.32, p = 0.02) in the NGT; with leptin levels ( R = 0.46, p = 0.001) in the IGT; and with adiponectin levels ( R = 0.25, p = 0.001) in all groups. In males, resistin and CRP exhibited significant correlations to insulin resistance ( R = 0.33, p = 0.005); in females significant correlation was demonstrated between insulin resistance and adiponectin ( R = 0.32, p = 0.003). Significant associations exist in the adipocytokine profiles of adults with different glucose tolerance. Conclusion Certain adipocytokines can be used not only as promising markers but also as potential adjunct therapy with regards to insulin sensitivity and obesity.

Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases., The hormone adiponectin is produced by fat cells and has positive metabolic effects. Here, Kim et al. show that DNA methyltransferase 1 (DNMT1) represses adiponectin expression through hypermethylation of its promoter, and that inflammatory cytokines enhance DNMT1 activity in obese mice and humans.

This study determined the effects of a high-fat meal on circulating endotoxin and cardiometabolic indices in adult Arab women. The cohort consisted of 92 consenting Saudi women (18 non-diabetic (ND)) control subjects, Age 24.4 ± 7.9 year, body mass index (BMI) 22.2 ± 2.2 Kg/m2), 24 overweight/obese (referred to as overweight-plus (overweight+)) subjects (Age 32.0 ± 7.8 year, BMI 28.5 ± 1.5 Kg/m2) and 50 type 2 diabetes mellitus (T2DM) patients (Age 41.5 ± 6.2 year, BMI 35.2 ± 7.7 Kg/m2). All were given a high-fat meal (standardized meal: 75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast of 12–14 h. Anthropometrics were obtained and fasting blood glucose, lipids, and endotoxin were serially measured for four consecutive postprandial hours. Endotoxin levels were significantly elevated prior to a high-fat meal in the overweight+ and T2DM than the controls (p &lt, 0.05). Furthermore, the postprandial cardiometabolic changes led to a more detrimental risk profile in T2DM subjects than other groups, with serial changes most notable in glucose, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol), and insulin levels (p-values &lt, 0.05). The same single meal given to subjects with different metabolic states had varying impacts on cardiometabolic health. Endotoxemia is exacerbated by a high-fat meal in Arab subjects with T2DM, accompanied by a parallel increase in cardiometabolic risk profile, suggesting disparity in disease pathogenesis of those with or without T2DM through the altered cardiometabolic risk profile rather than variance in metabolic endotoxinaemia with a high-fat meal.

Decay accelerating factor (DAF) is a widely distributed glycoprotein which aids in the inactivation of complement. DAF is also a cellular receptor for certain group B coxsackieviruses (CVB) and is responsible for the viral hemagglutinating activity for human red blood cells (RBC). Healthy, young female volunteers donated blood on days 11 and 22 of the ovarian cycle. Samples were categorized into luteal and follicular phases based on serum progesterone level (P4 either or = 2.0 ng/mL, luteal) and analyzed by flow cytomtery for DAF expression on RBC and CD21 + B lymphocytes. Cycling females showed significant variation in CVB-induced hemagglutination and % RBC or CD19 + cells which were DAF +. There was a strong correlation between serum estradiol levels and % RBC expressing DAF (P < 0.01) in the follicular, but not in the luteal ovarian phase. Infection of white blood cells with green-fluorescent protein CVB (GFP-CVB) showed a correlation between infectivity of CD19+ cells and DAF expression. This indicates that women may show differential susceptibility to CVB infection in the luteal and follicular phases of the ovarian cycle.

Bariatric surgery is the most successful therapeutic approach to weight loss, but how it leads to weight loss, and how it resolves obesity-related complications, including type-2 diabetes, are poorly understood. This study, comprising two groups of individuals, one on a low-calorie diet ( n = 5) and one undergoing bariatric surgery ( n = 7), used both targeted and untargeted proteomic approaches to determine changes in protein levels pre- and post-intervention (i.e. 3–6 months later). Changes were observed in both circulating and excreted proteins following weight loss. Targeted multiplexed biochip arrays measured 12 plasma peptides/proteins involved in metabolism and inflammation: C-peptide, ferritin, interleukin-6, interleukin-1 alpha, resistin, insulin, tumor necrosis factor alpha, leptin, plasminogen-activator inhibitor-1, adiponectin, cystatin C, and C-reactive protein. Following a low-calorie diet, plasma insulin and C-reactive protein levels were significantly reduced ( P = 0.045 and P = 0.030, respectively); adiponectin increased and leptin decreased following surgery ( P = 0.014 and P = 0.005, respectively). Untargeted proteomic analysis employing 2D difference in-gel electrophoresis (DIGE) showed 28 protein spots with ≥1.5-fold changes in expression following weight loss by a low-calorie diet; comparison of pre- and post-intervention urine samples from the bariatric surgery group showed changes in excretion of 110 protein spots. The combination of targeted protein analysis by multiplexed arrays and an exploratory (i.e. an unbiased or discovery) proteomic assessment of hundreds of proteins offers valuable insights into the mechanistic differences between alternative weight-loss strategies. This is a powerful hypothesis-generating approach to study complex, multifactorial syndromes such as obesity. The findings that arise from these studies can then be validated in targeted, hypothesis-directed investigations.

Atherosclerosis is a chronic inflammatory disease characterized by T lymphocyte infiltration into the atherosclerotic plaque. Assessments of T cell subtypes have demonstrated a predominance of CD4+ T helper (Th) cells, implicated Th1 and Th17 immunity in both human and mouse atherogenesis, and provided some evidence suggesting protective roles of Th2 and T regulatory cells. Observations that certain inbred mouse strains have an inherent T helper bias suggests a genetic predisposition toward developing a particular T helper phenotype. This review summarizes our current understanding of mechanisms of antigen processing for major histocompatibility complex (MHC) molecules, describes the different T helper cell subsets and their roles in atherosclerosis, and discusses mechanisms of genetic predisposition toward Th1/Th2 bias in mice. We also present data from our laboratory demonstrating inherent Th1/Th2 phenotypes in apparently healthy human volunteers that are stable over time, and discuss the potential implications for cardiovascular disease.

Background Although T‐helper type 1 (Th1) cells are considered important in atherosclerosis, the relationships between Th1 and Th2 cells and atherosclerosis have not been examined in population‐based studies. Methods and Results We measured Th cells as a percentage of lymphocytes by flow cytometry using CD 4 staining (% CD 4) in 917 participants of the Multi‐Ethnic Study of Atherosclerosis. We also measured interferon gamma–positive and interleukin‐4‐positive CD 4 + cells, representing Th1 and Th2 subpopulations (%Th1 and %Th2), respectively. We found that % CD 4 was 1.5% lower per 10 years of age ( P CD 4 and lower %Th1 and %Th2 values than other race/ethnic groups. Body mass index ( BMI ) and blood pressure were associated with % CD 4, but no traditional cardiovascular disease ( CVD ) risk factors were associated with %Th1 or %Th2. In multivariable models, the major independent variable associated with %Th1 was cytomegalovirus ( CMV ) antibody titer, with minor contributions from age, sex, seasonality, and interleukin‐6. In models with coronary artery calcification level as the outcome, significant independent variables included age, sex, smoking status, and %Th1 (β=0.25; P ≤0.01). Both %Th1 and %Th2 were associated with common carotid intimal media thickness (β=0.02 and −0.02, respectively; both P BMI . Conclusions Th1 bias is associated with subclinical atherosclerosis in a multiethnic population. The main Th1 correlate was CMV infectious burden. These findings are consistent with a role of Th1 cells in atherosclerosis and suggest the importance of prospective studies of T‐helper cell biasing in CVD .

Obesity and aging are interrelated conditions that both cause changes in adipocyte metabolism and affect the distribution of fat in both subcutaneous and visceral depots. In addition, both weight gain and aging can lead to similar clinical outcomes such as insulin resistance, cardiovascular disease, type 2 diabetes mellitus, atherosclerosis and stroke. Our objective was to examine the changes in protein expression within the subcutaneous adipose tissue of obese patients, matched for BMI, in relation to age. Mature adipocytes were isolated from liposuction samples of abdominal subcutaneous adipose tissue collected from both young (26.2±4.3 (mean age±SD); n=7) and old (52.2±4.7 (mean age±SD); n=7) obese individuals. Total protein extracts were then compared by two-dimensional difference in gel electrophoresis (2D DIGE). Thirty differentially expressed protein spots (ANOVA test, p≤0.05; fold-change ≥1.8) were detected, of which, 15 were identified by MALDI-TOF mass spectrometry. These were comprised of a total of thirteen unique protein sequences. Nine proteins were more abundant in the adipocytes isolated from old vs. young individuals. These proteins included prohibitin 1, protein disulphide isomerase A3, beta actin, profilin, aldo-ketoreductase 1 C2, alpha crystallin B and the annexins A1, A5 and A6. Four other proteins were less abundant in the adipocytes from old, obese subjects and these included keratin type 2 cytoskeletal 1, keratin type 2 cytoskeletal 10 and hemoglobins A and B. The differentially abundant proteins were investigated by Ingenuity Pathway Analysis (IPA) to reveal their associations with known biological functions. This analysis identified signal transducer and activator of transcription 3 as the central molecule in the connectivity map and the apoptotic pathway as the pathway with the highest score. Differences in the abundances of several proteins were confirmed by immunoblotting: i.e., prohibitin 1, protein disulphide isomerase A3, beta actin, profilin and signal transducer and activator of transcription 3 proteins. In conclusion, proteomic analysis of subcutaneous adipose tissue reveals differences in the abundance of proteins in adipocytes isolated from young vs. old individuals. These differentially abundant proteins are involved in the regulation of apoptosis, cellular senescence and inflammatory response. All these are common pathologic events in both obesity and aging.

During the past decades, it became obvious that reactive oxygen species (ROS) exert a multitude of biological effects covering a wide spectrum that ranges from physiological regulatory functions to damaging alterations participating in the pathogenesis of increasing number of diseases. This review summarizes the key roles played by the ROS in both health and disease. ROS are metabolic products arising from various cells; two cellular organelles are intimately involved in their production and metabolism, namely, the endoplasmic reticulum and the mitochondria. Updates on research that tremendously aided in confirming the fundamental roles of both organelles in redox regulation will be discussed as well. Although not comprehensive, this review will provide brief perspective on some of the current research conducted in this area for better understanding of the ROS actions in various conditions of health and disease.

Chemerin, a recognized chemoattractant, is expressed in adipose tissue and plays a role in adipocytes differentiation and metabolism. Gender- and adipose tissue-specific differences in human chemerin expression have not been well characterized. Therefore, these differences were assessed in the present study. The body mass index (BMI) and the circulating levels of chemerin and other inflammatory, adiposity and insulin resistance markers were assessed in female and male adults of varying degree of obesity. Chemerin mRNA expression was also measured in paired subcutaneous and visceral adipose tissue samples obtained from a subset of the study subjects. Serum chemerin concentrations correlated positively with BMI and serum leptin levels and negatively with high density lipoprotein (HDL)-cholesterol levels. No correlation was found between serum chemerin concentrations and fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, C-reactive protein or adiponectin. Similarly, no relation was observed with the homeostasis model assessment for insulin resistance (HOMA-IR) values. Gender- and adipose tissue-specific differences were observed in chemerin mRNA expression levels, with expression significantly higher in women than men and in subcutaneous than visceral adipose tissue. Interestingly, we found a significant negative correlation between circulating chemerin levels and chemerin mRNA expression in subcutaneous fat. Among the subjects studied, circulating chemerin levels were associated with obesity markers but not with markers of insulin resistance. At the tissue level, fat depot-specific differential regulation of chemerin mRNA expression might contribute to the distinctive roles of subcutaneous vs. visceral adipose tissue in human obesity.

Apoptosis within the placenta is increased in pregnancies complicated by pre-eclampsia (PE).This study aimed at evaluating the mitochondrial pathway of apoptosis in placenta of pregnant women with pre-eclampsia and correlate it with severity and pregnancy outcome . Apoptosis was assessed by measuring DNA fragmentation%,Bcl-2, p53 and caspase-9 in placental tissues from 25 pregnancies complicated by pre-eclampsia, and 25 placentas of normal pregnancy (NP). DNA fragmentation, p53 and caspase-9, were significantly increased while, Bcl-2 was significantly decreased in the placenta of pre-eclampsia group compared to control. No significant difference between mild and severe pre-eclampsia subgroups regarding these parameters could be found. DNA fragmentation was negatively correlated with Bcl-2 in PE group. Moreover, DNA fragmentation was negatively correlated with maternal age in both PE and control groups. A significant positive correlation between placental DNA fragmentation and gestational age in the NP group was observed. A significant negative correlation between caspase-9 activity, and fetal weight in PE group was found. It can be concluded that Hypoxia and ischemia induced by pre-eclampsia, up regulate p53 and reduce Bcl-2 expression with activation of caspase-9 and increasing DNA fragmentation in placental tissue. These results implicate the mitochondrial pathway in enhancing apoptosis in preeclamptic placenta and affecting fetal outcome but not the severity. Keywords : Apoptosis, p53, Bcl-2, Caspase-9, Mitochondria, Pre-eclampsia.

This study aims to identify which among the metabolic syndrome (MS) definitions are closely associated with pathological levels of leptin, adiponectin, resistin, tumour necrosis alpha (TNF-alpha) and C-reactive protein (CRP) among type 2 diabetics.Three hundred and five (160 males; 145 females) adult type 2 diabetic Saudis participated in this cross-sectional study. Leptin, adiponectin, resistin, TNF-alpha and CRP were analysed, using enzyme-linked immunosorbent assays (ELISA). Each participant was screened for MS based on the definitions of WHO, AHA/NHLBI and IDF.IDF holds the most identified patients [190 (62.3%)] in both, males [107 (66.9%)], and females [83 (57.2%)]. In males, hyperleptinemia, hypoadiponectinemia and hyperresistinemia were strongest in the AHA/NHLBI-defined MS [odds ratio (95% confidence interval 'CI') of 2.03 (1.05-3.93); 1.31 (0.55-3.1); 1.63 (0.42-6.4) respectively]. The risk of elevated CRP was highest on the WHO definition [odds ratio (95% CI) of 2.04 (0.46-9.04)]. In females, the IDF-defined MS has the strongest association in all four parameters: odds ratio (95% CI), as follows: leptin [2.09 (0.14-30.71)]; adiponectin [6.00 (0.47-76.17)]; resistin [0.47 (0.18-1.23)] and CRP [3.07 (0.21-45.10)].Gender differences exist in assessing the risk of various adipocytokine abnormalities in relation to the various criteria. This study supports the use of IDF definition among females and AHA/NHLBI in males in studies involving MS and obesity, since these definitions hold stronger predicting powers in detecting pathological levels of key adipocytokines.