Arsenic's shadowy influence: A systematic review of its carcinogenic role in gallbladder cancer.

INTRODUCTION: Gallbladder carcinoma (GBC) and cholangiocarcinoma are aggressive forms of cancer developed in the gallbladder and biliary tracts which are related to the liver. This systematic review aimed to highlight the significant association between gallbladder, biliary cancers, and arsenic exposure. METHODS: An extensive search was conducted in Embase, Cochrane, Scopus, PubMed, and Web of Science. We included studies that assessed arsenic levels in gallbladder cancer patients, without restrictions on age, sex, or language. Biological samples, such blood, bile, gallbladder tissue, gallstones, and hair were obtained, and arsenic levels were measured. Also, arsenic water and soil concentrations were collected. RESULTS: A total of 13 studies were included in our review. These studies included 2234 non-gallbladder carcinoma patients and 22 585 gallbladder carcinoma cases. The participant demographics showed a gender distribution of 862 males and 1845 females, with an age range of 20-75 years. The average body mass index (BMI) was 19.8 kg/m2 for nongallbladder carcinoma patients and 20.1 kg/m2 for gallbladder carcinoma cases. The selected studies examined arsenic concentrations across various biological samples, including blood, hair, gallstones, and bile. Blood arsenic levels ranged from 0.0002 to 0.3893 µg/g and were significantly associated with increased gallbladder carcinoma risk in several studies. Hair also demonstrated a significant correlation, with arsenic concentrations ranging from 0.0002 to 6.9801 µg/g. CONCLUSION: There is a strong link between arsenic exposure and gallbladder cancer or cholangiocarcinoma. Even chronic exposure to low-moderate amounts could lead to gallbladder carcinoma. These findings stress the need for more comprehensive and dedicated studies, to control arsenic water/soil levels and seek other preventive measures for this high mortality disease.

Impact of exercise on renal function, oxidative stress, and systemic inflammation among patients with type 2 diabetic nephropathy.

Background: Diabetic nephropathy (DN) is a prevalent microvascular diabetic complication all over the world. Objective: This study was designed to measure oxidative stress, systemic inflammation and kidney function response to exercise training in patients with type 2 diabetic (T2DM) nephropathy. Material and Methods: Eighty obese T2DM patients (50 males and 30 females), their body mass index (BMI) mean was 33.85±3.43 Kg/m2 and the mean of diabetes chronicity was 12.53±2.64 year participated in the present study and enrolled two groups; group I: received aerobic exercise training and group II: received no training intervention. Results: The mean values of creatinine, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were significantly decreased, while the mean values of interleukin-10 (IL-10), glutathione peroxidase (GPx) and glutathione (GSH) were significantly increased in group (A) after the aerobic exercise training, however the results of the control group were not significant. In addition, there were significant differences between both groups at the end of the study (P<0.05). Conclusion: There is evidence that aerobic exercise training modulated oxidative stress and inflammatory cytokines and improved renal function among patients with diabetic nephropathy.

The contribution of cooking appliances and residential traffic proximity to aerosol personal exposure.

PURPOSE: Indoor and outdoor factors affect personal exposure to air pollutants. Type of cooking appliance (i.e. gas, electricity), and residential location related to traffic are such factors. This research aims to investigate the effect of cooking with gas and electric appliances, as an indoor source of aerosols, and residential traffic as outdoor sources, on personal exposures to particulate matter with an aerodynamic diameter lower than 2.5 µm (PM2.5), black carbon (BC), and ultrafine particles (UFP). METHODS: Forty subjects were sampled for four consecutive days measuring personal exposures to three aerosol pollutants, namely PM2.5, BC, and UFP, which were measured using personal sensors. Subjects were equally distributed into four categories according to the use of gas or electric stoves for cooking, and to residential traffic (i.e. houses located near or away from busy roads). RESULTS/CONCLUSION: Cooking was identified as an indoor activity affecting exposure to aerosols, with mean concentrations during cooking ranging 24.7-50.0 µg/m3 (PM2.5), 1.8-4.9 µg/m3 (BC), and 1.4 × 104-4.1 × 104 particles/cm3 (UFP). This study also suggest that traffic is a dominant source of exposure to BC, since people living near busy roads are exposed to higher BC concentrations than those living further away from traffic. In contrast, the contribution of indoor sources to personal exposure to PM2.5 and UFP seems to be greater than from outdoor traffic sources. This is probably related to a combination of the type of building construction and a varying range of activities conducted indoors. It is recommended to ensure a good ventilation during cooking to minimize exposure to cooking aerosols. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40201-020-00604-7.

Aerobic versus resistance exercises on systemic inflammation and sleep parameters in obese subjects with chronic insomnia syndrome.

BACKGROUND: Chronic primary insomnia is a prevalent sleep disorder that is associated with adverse effects on health outcomes. Exercise is often considered a non-pharmacological approach that could have beneficial effects on sleep. OBJECTIVE: The aim of the study was to compare the impact of aerobic and resistance exercise training on quality of sleep and inflammatory markers among subjects with chronic primary insomnia. MATERIAL AND METHODS: Sixty previously sedentary subjects with chronic primary insomnia subjects enrolled in this study, their age ranged from 31-52 years. All participants were randomly assigned to aerobic exercise intervention group (group A, n=35) or resistance exercise intervention group (group B, n=35). Polysomnographic recordings for sleep quality assessment, IL-6, IL-10 and TNF-α were measured before and at the end of the study after six months. RESULTS: There was a significant increase in the total sleep duration, sleep efficiency, sleep onset latency and IL-10 in group(A) and group (B) in addition to significant reduction in awake time after sleep onset, REM latency, IL-6 and TNF-α after 6 months of aerbic and resistance exercise training. However, there were significant differences between both groups at the end of the study. CONCLUSION: Aerobic exercise training is more appropriately than resistance exercise training in modulation of inflammatory and sleep quality among subjects with chronic primary insomnia.

Inflammatory cytokines and sleep parameters response to life style intervention in subjects with obese chronic insomnia syndrome.

BACKGROUND: Chronic primary insomnia is a prevalent sleep disorder that is associated with adverse effects on health outcomes. Sleep disturbance is usually associated with abnormal level of systemic inflammation biomarkers. OBJECTIVE: The aim of this study was to detect changes in sleep quality and inflammatory markers following weight loss among subjects with chronic primary insomnia. MATERIAL AND METHODS: Eighty previously sedentary subjects with chronic primary insomnia subjects enrolled in this study, their age ranged from 32-51 year were randomly assigned to life style intervention group (group A, n=40) or control group (group B, n=40). Polysomnographic recordings for sleep quality assessment, IL-6, IL-10 and TNF-α were measured before and at the end of the study after six months. RESULTS: There was a significant increase in the total sleep duration, sleep efficiency, sleep onset latency and IL-10 in addition to significant reduction in awake time after sleep onset, REM latency, IL-6 and TNF-α after 6 months of in group(A) as a result of weight loss program; while the results of the control group (group B) were not significant. Also, there were significant differences between both groups at the end of the study. CONCLUSION: Life style intervention modulates systemic inflammatory parameters and sleep quality among subjects with chronic primary insomnia.

Weight reduction improves immune system and inflammatory cytokines in obese asthmatic patients.

BACKGROUND: Activation of immunological and systemic inflammation markers are common in obesity and asthma. OBJECTIVE: The target of this study was to assess impact of weight reduction on immunological and systemic inflammation markers in obese asthma patients. MATERIAL AND METHODS: Eighty asthmatic patients of both sex; their age and body mass index (BMI) mean were 38.72 ± 7.14 year and 32.65 ± 3.18 Kg/m2 respectively. Exclusion criteria included smokers, infections, vaccinations, cancer, surgery, immune system disorders and medications that may influence immune system function as anti-inflammatory medications, analgesics and anti-depressant. All subjects were randomly enrolled in weight reduction group (group A) or control group (group B). RESULTS: The main findings in the present study indicated that weight reducing program in group (A) was associated with significant reduction in the mean values of IL6, TNF-α, and IL8 in addition to significant increase in the mean values of CD4 and CD8 cell count . However, findings of group (B) showed no significant changes. Moreover, Comparison between both groups at the end of the study revealed significant differences. CONCLUSION: Weight reduction improved immunological and systemic inflammation markers in obese asthma patients.

Aerobic exercise affects sleep, psychological wellbeing and immune system parameters among subjects with chronic primary insomnia.

BACKGROUND: Chronic primary insomnia is characterized by long-term difficulties in maintaining and initiating sleep, too early waking up, poor mood, fatigue, impaired concentration and poor quality of life. Exercise training is recommended to prevent and alleviate sleep disorders. OBJECTIVE: The aim of the study was to investigate the influence of aerobic exercise training on quality of sleep, psychological wellbeing and immune system among subjects with chronic primary insomnia. MATERIAL AND METHODS: Eighty previously sedentary subjects with chronic primary insomnia subjects enrolled in this study, their age ranged from 35-56 years. All participants were randomly assigned to supervised aerobic exercise intervention group (group A, n=40) or control group (group B, n=40). Polysomnographic recordings for sleep quality assessment, Beck Depression Inventory (BDI), Profile of Mood States(POMS), Rosenberg Self-Esteem Scale (RSES), number of CD3+, CD4+, CD8+ T cells count and CD4/CD8 ratio were measured before and at the end of the study after six months. RESULTS: There was a significant increase in the total sleep duration, sleep efficiency and sleep onset latency in group(A) after six months of aerobic exercise training, while, wake time after sleep onset and rapid eye movement (REM) latency significantly reduced after six months of aerobic training compared with values obtained prior to aerobic exercise training. Also, the mean values of BDI, POMS, CD3 count, CD4 count and CD8 count decreased significantly and the mean value of RSES significantly increased in group (A) after the aerobic exercise training, while the results of the control group were not significant. Moreover, there were significant differences between both groups at the end of the study. CONCLUSION: Exercise training can be considered as a non-pharmacological modalty for modifying sleep quality, psychological wellbeing and immune system among subjects with chronic primary insomnia.

Weight reduction ameliorates inflammatory cytokines, adipocytokines and endothelial dysfunction biomarkers among Saudi patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) considered as one of the cardiovascular disorders (CVD) principle risk factor as diabetes is associated with abnormal levels of endothelial function, inflammatory and adipocytokines. OBJECTIVE: The aim of this study was to measure the impact of weight reducing on inflammatory cytokines, adipocytokines and endothelial function biomarkers among obese T2DM patients. METHODS: One-hundred T2DM patients enrolled in the present study; the age range was 35-55 year. Participants shared in this study were enrolled in group (A) received diet control and aerobic exercise on treadmill, while, group (B) had no intervention for 3 months. RESULTS: The mean values of body mass index (BMI), tumor necrosis factor -alpha (TNF-α), interleukin-6 (IL-6), leptin, inter-cellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), E-selectin and plasminogen activator inhibitor-1 activity (PAI-1 activity) were significantly decreased and adiponectin was increased significantly in the training group, however the results of the control group were not significant. Also, there were significant differences between both groups at the end of the study. CONCLUSION: Weight reducing program modulates inflammatory cytokines, adipocytokines and endothelial function biomarkers among obese T2DM patients.

Aerobic exercise modulates cytokine profile and sleep quality in elderly.

BACKGROUND: Sleep disturbance is a major problem for older adults which can be exacerbated by increased inflammation as aging is associated with increased circulating pro-inflammatory and lower anti-inflammatory cytokines. There is a need to develop alternative medicine techniques to help improve sleep quality in the elderly. OBJECTIVE: To investigate the effects of aerobic exercise training on the sleep quality and inflammatory cytokines in elderly subjects. MATERIAL AND METHODS: Forty previously sedentary elderly subjects participated in this study, their age ranged from 61- 67 years. All subjects were randomly assigned to supervised aerobic exercise intervention group (group A, n=25) or control group (group B, n=25). Polysomnographic recordings for sleep quality assessment, interleukin- 6 (IL-6), tumor necrosis factor- alpha (TNF-α) and interleukin-10 (IL-10) were measured before and after 6 months at the end of the study. RESULTS: There was a significant increase in total sleep duration, sleep efficiency and sleep onset latency in group(A) after 6 months of aerobic exercise training, while, wake time after sleep onset and rapid eye movement (REM) latency significantly reduced after 6 months of aerobic training compared with values obtained prior to aerobic exercise training. Also, the mean values of TNF- α and IL-6 decreased significantly and the mean value of IL-10 significantly increased in group (A) after the aerobic exercise training, however the results of the control group were not significant. Moreover, there were significant differences between both groups at the end of the study. CONCLUSION: Exercise training can be considered as a non-pharmacological modality for modifying sleep quality and inflammation among elderly.

Effects of short-term exposure to particulate matter air pollution on cognitive performance.

This paper assesses the effect of short-term exposure to particulate matter (PM) air pollution on human cognitive performance via a double cross over experimental design. Two distinct experiments were performed, both of which exposed subjects to low and high concentrations of PM. Firstly, subjects completed a series of cognitive tests after being exposed to low ambient indoor PM concentrations and elevated PM concentrations generated via candle burning, which is a well-known source of PM. Secondly, a different cohort underwent cognitive tests after being exposed to low ambient indoor PM concentrations and elevated ambient outdoor PM concentrations via commuting on or next to roads. Three tests were used to assess cognitive performance: Mini-Mental State Examination (MMSE), the Stroop Color and Word test, and Ruff 2 & 7 test. The results from the MMSE test showed a statistically robust decline in cognitive function after exposure to both the candle burning and outdoor commuting compared to ambient indoor conditions. The similarity in the results between the two experiments suggests that PM exposure is the cause of the short-term cognitive decline observed in both. The outdoor commuting experiment also showed a statistically significant short-term cognitive decline in automatic detection speed from the Ruff 2 and 7 selective attention test. The other cognitive tests, for both the candle and commuting experiments, showed no statistically significant difference between the high and low PM exposure conditions. The findings from this study are potentially far reaching; they suggest that elevated PM pollution levels significantly affect short term cognition. This implies average human cognitive ability will vary from city to city and country to country as a function of PM air pollution exposure.

Impact of aerobic exercise versus resisted exercise on endothelial activation markers and inflammatory cytokines among elderly.

BACKGROUND: Aging is the major risk factor for the development of cardiovascular diseases as aging increases plasma levels of pro-inflammatory mediators and endothelial dysfunction. Physical exercise is a potential strategy for improving the endothelial dysfunction and chronic inflammation that accompanies aging. However, there is a need to differentiate between aerobic and resistance exercise training regarding endothelial activation markers and systemic inflammation among elderly population. OBJECTIVE: The aim of this study was to compare the impact of six months of aerobic versus resisted exercise training on inflammatory cytokines and endothelial activation markers among elderly. MATERIAL AND METHODS: Eighty previously sedentary elderly subjects participated in this study, their age ranged from 61-66 years. All subjects were randomly assigned to supervised aerobic exercise intervention group (group A, n=40) or resistance exercise group (group B, n=40). RESULTS: The mean value of interleukin-10 (IL-10) was significantly increased, where the mean value of inter-cellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), E-selectin, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were significantly decreased in group (A) and group (B). In addition, there were significant differences in the mean levels of the investigated parameters between group (A) and group (B) at the end of the study. CONCLUSION: The current study provides evidence that aerobic exercise is more appropriate in modulate entering altered endothelial activation and inflammatory markers than resisted exercise among elderly population.

Impact of aerobic versus resisted exercise training on systemic inflammation biomarkers and quality of Life among obese post-menopausal women.

BACKGROUND: Although post-menopausal obesity is an important public national health problem in Saudi Arabia, to date no study has evaluated the effects of weight reduction on biochemical & clinical parameters and quality of Life for obese Saudi post-menopausal women. OBJECTIVE: The aim of this study was examine the effects of aerobic versus resisted exercise training effects upon systemic inflammation biomarkers and quality of life for obese post-menopausal Saudi women. MATERIAL AND METHODS: One hundred Saudi post-menopausal obese women participated in this study, their age ranged from 50-58 years and their body mass index (BMI) ranged from 30-35 kg/m2. All participants were divided into two equal groups: The first group received aerobic exercise training on treadmill where, the second group received resisted exercise training. Health-related quality of life (SF-36 HRQL), tumor necrosis factor- alpha(TNF-α), Interleukin-2(IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6) and C-reactive protein (CRP) were measured before and after 3 months at the end of the study. RESULTS: The mean values of SF-36 HRQL subscale scores were significantly increased, while the mean value of TNF-α, Il-2, IL-4, IL-6, CRP and BMI were significantly decreased in both groups after treatments. There were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment with more changes in patients received aerobic exercise training. CONCLUSION: The current study provides evidence that aerobic exercise is more appropriate than resisted exercise training in modulating inflammatory cytokines and quality of life among obese post-menopausal women.

A rare variety of congenital adrenal hyperplasia with mosaic Klinefelter syndrome: a unique combination presenting with ambiguous genitalia and sexual precocity

Congenital adrenal hyperplasia (CAH) due to the three-beta-hydroxysteroid-dehydrogenase (3ß-HSD) enzyme deficiency is a rare autosomal recessive disorder presenting with sexual precocity in a phenotypic male. Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy presenting with hypergonadotropic hypogonadism in a male. However, only a handful of cases of mosaic KS have been described in the literature. The co-existence of mosaic KS with CAH due to 3ß-HSD enzyme deficiency portrays a unique diagnostic paradox where features of gonadal androgen deficiency are masked by simultaneous adrenal androgen excess. Here, we report a 7-year-old phenotypic male boy who, at birth presented with ambiguous genitalia, probably a microphallus with penoscrotal hypospadias. Later on, he developed accelerated growth with advanced bone age, premature pubarche, phallic enlargement and hyperpigmentation. Biochemically, the patient was proven to have CAH due to 3ß-HSD deficiency. However, the co-existence of bilateral cryptorchidism made us to consider the possibility of hypogonadism as well, and it was further explained by concurrent existence of mosaic KS (47,XXY/46,XX). He was started on glucocorticoid and mineralocorticoid replacement and underwent right-sided orchidopexy on a later date. He showed significant clinical and biochemical improvement on subsequent follow-up. However, the declining value of serum testosterone was accompanied by rising level of FSH thereby unmasking hypergonadotropic hypogonadism due to mosaic KS. In future, we are planning to place him on androgen replacement as well. Learning points: •• Ambiguous genitalia with subsequent development of sexual precocity in a phenotypic male points towards some unusual varieties of CAH. •• High level of serum testosterone, adrenal androgen, plasma ACTH and low basal cortisol are proof of CAH, whereas elevated level of 17-OH pregnenolone is biochemical marker of 3ß-HSD enzyme deficiency. •• Final diagnosis can be obtained with sequencing of HSD3B2 gene showing various mutations. •• Presence of bilateral cryptorchidism in such a patient may be due to underlying hypogonadism. •• Karyotyping in such patient may rarely show mosaic KS (47,XXY/46,XX) and there might be unmasking of hypergonadotropic hypogonadism resulting from adrenal androgen suppression from glucocorticoid treatment.

Impact of aerobic exercises on selected inflammatory markers and immune system response among patients with sickle cell anemia in asymptomatic steady state.

BACKGROUND & OBJECTIVE: Sickle cell anemia (SCA) is well recognized as a chronic inflammatory disease. Despite progress in therapy, SCA remains a cause of significant morbidity and mortality. The relationship between exercise and immune function has been of great interest to the scientific community and the lay public. The aim of this study was to measure the impact of aerobic exercise training on the immunologic parameters and inflammatory cytokines of patients with sickle cell anemia (SCA) in asymptomatic steady state. MATERIAL AND METHODS: Sixty asymptomatic sickle cell anemia patients were involved in this study, their age ranged from 25- 40 years and were assigned to two sub-groups; group (A) received aerobic exercise training for 12 weeks, however group (B) received no training intervention for 12 weeks. Parameters of CD3, CD4 and CD8 were quantified, Leukocyte, differential counts, IL-6 and TNF-α were measured before and after 12 weeks, at the end of the study. RESULTS: The mean values of CD3, CD4 and CD8, leukocyte, monocytes counts, IL-6 and TNF-α were significantly decreased in group (A), while group (B) showed non-significant changes in these parameters. Also; there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment. CONCLUSION: The current study provides evidence that aerobic exercise training improves inflammatory markers and immune system in patients with sickle cell anemia (SCA) in asymptomatic steady state.

Inflammatory cytokines and immune system modulation by aerobic versus resisted exercise training for elderly.

BACKGROUND: Aging is characterized with immunosenescence associated with a hyper-inflammatory state, characterized by elevated circulating levels of pro-inflammatory mediators. Physical exercise is a potential strategy for improving the immune system dysfunction and chronic inflammation that accompanies aging. However, there is a need to differentiate between aerobic and resistance exercise training regarding human immune system and systemic inflammation among the elderly Saudi population. OBJECTIVE: The aim of this study was to compare the impact of 6 months of aerobic versus resisted exercise training on inflammatory cytokines and immune system response among elderly. MATERIAL AND METHODS: Sixty previously sedentary elderly subjects participated in this study, their age ranged from 61-66 years. All Subjects were randomly assigned to supervised aerobic exercise intervention group (group A, n=40) or resistance exercise group (group B, n=40). Number of CD3+,CD4+,CD8+ T cells count and CD4/CD8 ratio were quantified, IL-6, TNF-α and IL10 were measured before and after 6 months, at the end of the study. RESULTS: The mean values of CD3+, CD4+ and CD8+ T cells count and IL-10 were significantly increased, whereas the mean values of CD4/CD8 ratio, IL-6 and TNF-α were significantly decreased in group (A) and group (B). Also; there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment. CONCLUSION: The current study provides evidence that aerobic exercise is more appropriate in modulating the immune system and inflammatory markers among the elderly population.

Impact of weight reduction on selected immune system response among Hepatitis C virus Saudi patients.

BACKGROUND: Recently, about 2.35% of the world populations are estimated to be chronically infected with hepatitis C virus (HCV). Previous cohort studies indicated that obesity increases risk of hepatic steatosis and fibrosis in non-diabetic patients with chronic hepatitis C infection due to diminished response to anti-viral therapy and as a result obesity is considered as an important factor in the progression of chronic HCV. However, there is a strong association between BMI and the human immune system among HCV patients. OBJECTIVE: This study aimed to examine effects of weight reduction program on selected immune parameters among HCV Saudi patients. MATERIAL AND METHODS: One-hundred obese Saudi patients with chronic HCV infection participated in this study, their age ranged from 50-58 years and their body mass index (BMI) ranged from 30-35 kg/m2. All Subjects were included in two groups: The first group received weight reduction program in the form of treadmill aerobic exercises in addition to diet control whereas, the second group received no therapeutic intervention. Parameters of CD3, CD4 and CD8 were quantified; Leukocyte, differential counts and BMI were measured before and after 3 months, at the end of the study. RESULTS: The mean values of BMI, white blood cells, total neutrophil count, monocytes, CD3, CD4 and CD8 were significantly decreased in the training group as a result of weight loss program; however the results of the control group were not significant. Also, there were significant differences between both groups at the end of the study. CONCLUSION: Weight loss modulates immune system parameters of patients with HCV.

Impact of weight reduction on insulin resistance, adhesive molecules and adipokines dysregulation among obese type 2 diabetic patients.

BACKGROUND: Type 2 diabetes mellitus is usually related to vascular problems and is associated with impairment in endothelial function characterized by impaired endothelial-dependent vasodilation and increased platelet adhesion. There is limitation in clinical studies that have addressed the beneficial effects of weight reduction in modulating biomarkers of endothelial dysfunction and adipokines dysregulation for obesity associated with type 2 diabetes mellitus. OBJECTIVE: This study was designed to detect the effects of weight loss on insulin resistance, adhesive molecules and adipokines dysregulation in obese type 2 diabetic patients. METHODS: Eighty obese patients with type 2 diabetes mellitus, their age ranged from 35-55 years and their body mass index ranged from 31-37 kg/m2 were equally assigned into 2 groups: the weight reduction group received aerobic exercises in addition to diet regimen, where the control group received medical treatment only for 12 weeks. RESULTS: There was a 24.04%, 19.33%, 22.78% ,12.28%, 9.35%, 22.53% & 10.12 % reduction in mean values of Homeostasis Model Assessment-Insulin Resistance Index (HOMA-IR), Leptin, Adiponectin, Resistin, intercellular cell adhesion molecule -1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin & body mass index (BMI) respectively in addition to 26.20% & 24.58% increase in the mean values of adiponectin & the quantitative insulin-sensitivity check index (QUICKI) respectively in group (A) at the end of the study. The mean values of leptin, resistin, insulin, HOMA-IR, ICAM-1, VCAM-1, E-selectin & BMI were significantly decreased in addition to significant increase in the mean values of adiponectin & QUICKI in group (A) those that received aerobic exercise training in addition to diet regimen. While the results of group (B) those that received no treatment intervention were not significant. In addition, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment (P<0.05). CONCLUSION: Within the limit of this study, 10% reduction in body mass index modulates insulin resistance, adhesive molecules and adipokines dysregulation among obese type 2 diabetic patients.

Hydrogen peroxide production is affected by oxygen levels in mammalian cell culture.

Although oxygen levels in the extracellular space of most mammalian tissues are just a few percent, under standard cell culture conditions they are not regulated and are often substantially higher. Some cellular sources of reactive oxygen species, like NADPH oxidase 4, are sensitive to oxygen levels in the range between 'normal' physiological (typically 1-5%) and standard cell culture (up to 18%). Hydrogen peroxide in particular participates in signal transduction pathways via protein redox modifications, so the potential increase in its production under standard cell culture conditions is important to understand. We measured the rates of cellular hydrogen peroxide production in some common cell lines, including C2C12, PC-3, HeLa, SH-SY5Y, MCF-7, and mouse embryonic fibroblasts (MEFs) maintained at 18% or 5% oxygen. In all instances the rate of hydrogen peroxide production by these cells was significantly greater at 18% oxygen than at 5%. The increase in hydrogen peroxide production at higher oxygen levels was either abolished or substantially reduced by treatment with GKT 137831, a selective inhibitor of NADPH oxidase subunits 1 and 4. These data indicate that oxygen levels experienced by cells in culture influence hydrogen peroxide production via NADPH oxidase 1/4, highlighting the importance of regulating oxygen levels in culture near physiological values. However, we measured pericellular oxygen levels adjacent to cell monolayers under a variety of conditions and with different cell lines and found that, particularly when growing at 5% incubator oxygen levels, pericellular oxygen was often lower and variable. Together, these observations indicate the importance, and difficulty, of regulating oxygen levels experienced by cells in culture.

Topical bioavailability of diclofenac from locally-acting, dermatological formulations.

Assessment of the bioavailability of topically applied drugs designed to act within or beneath the skin is a challenging objective. A number of different, but potentially complementary, techniques are under evaluation. The objective of this work was to evaluate in vitro skin penetration and stratum corneum tape-stripping in vivo as tools with which to measure topical diclofenac bioavailability from three approved and commercialized products (two gels and one solution). Drug uptake into, and its subsequent clearance from, the stratum corneum of human volunteers was used to estimate the input rate of diclofenac into the viable skin layers. This flux was compared to that measured across excised porcine skin in conventional diffusion cells. Both techniques clearly demonstrated (a) the superiority in terms of drug delivery from the solution, and (b) that the two gels performed similarly. There was qualitative and, importantly, quantitative agreement between the in vitro and in vivo measurements of drug flux into and beyond the viable skin. Evidence is therefore presented to support an in vivo - in vitro correlation between methods to assess topical drug bioavailability. The potential value of the stratum corneum tape-stripping technique to quantify drug delivery into (epi)dermal and subcutaneous tissue beneath the barrier is demonstrated.

Impact of weight loss on oxidative stress and inflammatory cytokines in obese type 2 diabetic patients.

BACKGROUND: Type 2 diabetes mellitus is associated with abnormal markers of inflammatory cytokines and oxidative stress markers. Although, these abnormalities could be modulated with weight reduction; there is limitation in clinical studies that have addressed the beneficial effects of weight reduction in modulating biomarkers of inflammatory cytokines and oxidative stress for obesity associated with type 2 diabetes mellitus. OBJECTIVE: This study was designed to detect the effects of weight loss on the inflammatory cytokines, oxidative stress markers in obese type 2 diabetic patients. MATERIAL AND METHODS: Eighty obese patients with type 2 diabetes mellitus, their age ranged from 35-57 years and their body mass index ranged from 31-35 kg/m2 were equally assigned into 2 groups: the weight reduction group received aerobic exercises, diet regimen, where as the control group received medical treatment only for 12 weeks. RESULTS: The mean values of body mass index (BMI), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (sCRP), conjugated dienes (CD) and malondialdehyde (MDA) were significantly decreased, while the mean values of glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione (GSH) were significantly increased in patients of group (A), while changes were not significant in group (B). Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study. CONCLUSION: Weight loss ameliorates inflammatory cytokines and oxidative stress markers in obese type 2 diabetic patients.