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- Adipocyte cell size, free fatty acids and apolipoproteins are associated with non-alcoholic liver injury progression in severely obese patients. [JOURNAL ARTICLE]
- Metabolism 2014 Sep 6.
Obesity is a modern pandemic with continuous expansion and represents an independent risk factor for non-alcoholic fatty liver disease (NAFLD), the most common liver disease in westernized countries. The crosstalk between adipose tissue and the liver is key to the development of NAFLD.Therefore, in an observational study blood, visceral adipose tissue and liver tissue were obtained from 93 severely obese patients with a mean age of 43years and mean BMI of 52kg/m(2) at the time of weight loss surgery. In a subset of patients a follow-up blood sample was obtained 6weeks after surgery to assess acute effects of weight loss. In addition to routine parameters of liver injury, serum samples were analyzed for leptin, adiponectin, free fatty acids (FFAs), and several apolipoproteins.The diameter of visceral adipocytes correlated to liver injury, serum markers of inflammation and serum adipokine levels. Liver injury assessed by serology (ALT, AST) and histology (NAFLD activity score, NAS) was independent of the BMI. However, serum levels of triglycerides and Apolipoprotein CIII (ApoCIII) were associated with NAS. Serum levels and composition of FFAs, especially long chain FFAs, also correlated with NAS. Analysis of serum samples six weeks after surgery revealed beneficial changes in serum triglycerides, levels of ApoCIII and several FFAs.In severely obese patients beneficial effects on liver injury can been observed as early as six weeks after bariatric surgery. These effects may be explained by the observed changes in adipose tissue and lipid metabolism. Collectively, these findings underline the importance of the link between adipose tissue and the liver.
- Dietary administration of laminarin improves the growth performance and immune responses in Epinephelus coioides. [JOURNAL ARTICLE]
- Fish Shellfish Immunol 2014 Sep 26.
This study was conducted to evaluate the effects of laminarin on the growth performance, immunological and biochemical parameters, as well as immune related genes expression in the grouper, Epinephelus coioides. One hundred and eight fish were randomly divided into four groups (45 groupers/group). Blank control group was fed with the basal diet, while low, medium and high doses of laminarin groups were fed with the basal diet supplemented with 0.5%, 1.0%, and 1.5% laminarin, respectively, for 48 days. The immunological and biochemical parameters in blood were investigated. The mRNA levels of IL-1β, IL-8, and TLR2 in midgut were also evaluated by quantitative real-time PCR. Dietary laminarin supplementation significantly improved the specific growth rate and the feed efficiency ratio of the fish. The level of TP and the activity of LZM, CAT and SOD were higher than that of the control. The levels of UREA and CREA as well as the activity of ALP were lower than of the control. There was no significant difference in the levels of ALT and AST between control groups and treated groups. In addition, dietary laminarin supplementation decreased the levels of C3 and C4. The expression of immune response genes IL-1β, IL-8, and TLR2 showed significant increases (P<0.05) in groupers fed low dose (0.5%) and medium dose (1.0%) of laminarin compared with the blank control. These results suggest that laminarin modulates the immune response and stimulates growth of the fish.
- Common Variants in the CRP Promoter are Associated with a High C-Reactive Protein Level in Kawasaki Disease. [JOURNAL ARTICLE]
- Pediatr Cardiol 2014 Sep 30.
Kawasaki disease (KD) is an acute self-limiting form of vasculitis that afflicts infants and children and manifests as fever and signs of mucocutaneous inflammation. Children with KD show various laboratory inflammatory abnormalities, such as elevations in their white blood cell (WBC) count, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). We here performed a genome-wide association study (GWAS) of 178 KD patients to identify the genetic loci that influence 10 important KD laboratory markers: WBC count, neutrophil count, platelet count, CRP, ESR, hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and total protein. A total of 165 loci passed our arbitrary stage 1 threshold for replication (p < 1 × 10(-5)). Of these, only 2 SNPs (rs12068753 and rs4786091) demonstrated a significant association with the CRP level in replication study of 473 KD patients (p < 0.05). The SNP located at the CRP locus (rs12068753) demonstrated the most significant association with CRP in KD patients (beta = 4.73 and p = 1.20 × 10(-6) according to the stage 1 GWAS; beta = 3.65 and p = 1.35 × 10(-8) according to the replication study; beta = 3.97 and p = 1.11 × 10(-13) according to combined analysis) and explained 8.1 % of the phenotypic variation observed. However, this SNP did not demonstrate any significant association with CRP in the general population (beta = 0.37 and p = 0.1732) and only explained 0.1 % of the phenotypic variation in this instance. Furthermore, rs12068753 did not affect the development of coronary artery lesions or intravenous immunoglobulin resistance in KD patients. These results indicate that common variants in the CRP promoter can play an important role in the CRP levels in KD.
- Lack of persistent hepatitis E virus infection as a cause for unexplained transaminase elevation in renal transplant recipients in India. [JOURNAL ARTICLE]
- Indian J Gastroenterol 2014 Oct 1.
Hepatitis E virus (HEV) infection is highly endemic in India, being the most common cause of acute hepatitis; however, no case of chronic infection has been reported. All the human isolates of HEV from India till date have belonged to genotype 1. In contrast, in non-endemic areas, genotype 3 is the most prevalent, and persistent HEV infection has been reported among solid-organ transplant recipients. Whether persistent infection occurs with genotype 1 HEV is unclear. We therefore looked for evidence of HEV infection among renal transplant recipients with elevated alanine transaminase (ALT).Renal transplant recipients receiving immunosuppressive therapy were screened for ALT levels, irrespective of time duration since renal transplant. For those with ALT levels equal to or exceeding 50 IU/mL on at least two occasions ≥3 weeks apart, serum was tested for HEV RNA using a sensitive real-time reverse transcription polymerase chain reaction assay. For those testing positive, HEV genotyping and follow up for duration of viral persistence were planned.Of the 275 patients studied, 49 (17.8 %, 44 male, median age = 39.5 years) had elevated ALT levels (median = 62 [range = 50-477] IU/L). None of these 49 patients had detectable HEV RNA in the serum using an assay with detection sensitivity of 300 copies of RNA/mL of specimen.Our data indicate that persistent HEV infection is an infrequent cause of ALT elevation in Indian renal transplant recipients who are receiving immunosuppressive drugs. This suggests that infection with genotype 1 HEV may have either no or low potential to cause persistent infection.
- Normal Alanine Transferase: an Independent Indicator of Adiposity Related Comorbidity Risk in Youth. [JOURNAL ARTICLE]
- J Diabetes 2014 Sep 30.
Elevated levels of alanine aminotransferase (ALT) are associated with obesity and are often a consequence of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to assess the relationship between ALT and risk factors for adiposity-related co-morbidities in a diverse population of middle school children.We measured height, weight, body fatness (bioelectrical impedance), waist circumference, insulin sensitivity, phase 1 insulin release (acute insulin response following intravenous glucose), beta-cell function (acute insulin response corrected for insulin sensitivity), ALT, lipid profiles, and circulating concentrations of IL-6, C-reactive protein, adiponectin, and TNF-α in a multi-ethnic/racial population of 106 middle school students (age 11-14 years, 45F) of varying BMI.ALT was significantly correlated with BMI, % body fat, fat mass, waist circumference, fasting insulin, insulin resistance, triglycerides, and was inversely correlated with HDL in children, even though all values of ALT were "normal" (range of 4.0-33.0 U/L). ALT was significantly higher in males than females even when corrected for body fatness. Significant correlations with lipids and insulin resistance persisted even when adjusted for age, gender, and body fatness.Even within the normative range, ALT levels were significantly correlated with anthropomorphic and biochemical risk factors for adiposity-related co-morbidities in youth. Therefore, because ALT is correlated with dyslipidemia, insulin resistance, and central fat distribution, it might also serve as a marker of risk for adiposity-related co-morbidities beyond NAFLD.
- N-Acetylcysteine Attenuates Ischemia-Reperfusion-Induced Apoptosis and Autophagy in Mouse Liver via Regulation of the ROS/JNK/Bcl-2 Pathway. [Journal Article]
- PLoS One 2014; 9(9):e108855.
Hepatic ischemia-reperfusion injury (HIRI) remains a pivotal clinical problem after hemorrhagic shock, transplantation, and some types of toxic hepatic injury. Apoptosis and autophagy play important roles in cell death during HIRI. It is also known that N-acetylcysteine (NAC) has significant pharmacologic effects on HIRI including elimination of reactive oxygen species (ROS) and attenuation of hepatic apoptosis. However, the effects of NAC on HIRI-induced autophagy have not been reported. In this study, we evaluated the effects of NAC on autophagy and apoptosis in HIRI, and explored the possible mechanism involved.A mouse model of segmental (70%) hepatic warm ischemia was adopted to determine hepatic injury. NAC (150 mg/kg), a hepatoprotection agent, was administered before surgery. We hypothesized that the mechanism of NAC may involve the ROS/JNK/Bcl-2 pathway. We evaluated the expression of JNK, P-JNK, Bcl-2, Beclin 1 and LC3 by western blotting and immunohistochemical staining. Autophagosomes were evaluated by transmission electron microscopy (TEM).We found that ALT, AST and pathological changes were significantly improved in the NAC group. Western blotting analysis showed that the expression levels of Beclin 1 and LC3 were significantly decreased in NAC-treated mice. In addition, JNK, p-JNK, Bax, TNF-α, NF-κB, IL2, IL6 and levels were also decreased in NAC-treated mice.NAC can prevent HIRI-induced autophagy and apoptosis by influencing the JNK signal pathway. The mechanism is likely to involve attenuation of JNK and p-JNK via scavenged ROS, an indirect increase in Bcl-2 level, and finally an alteration in the balance of Beclin 1 and Bcl-2.
- Natural History and Response to Treatment of HCV Infection Among Egyptian Survivors of Childhood Malignancy. [JOURNAL ARTICLE]
- Pediatr Hematol Oncol 2014 Sep 29.
Background: Children with cancer are at a high risk for hepatitis C virus infection due to immunosuppression secondry to chemotherapy and multiple transfusions of blood products. We aim to evaluate the presence of HCV infection in children with malignant diseases, risk factors, clinical course, laboratory, histopathological findings, and response to HCV treatment. Method: We described 31 patients referred to the pediatric hepatology clinic at Cairo University pediatric hospital and presenting with postmalignant virus C infection. Data collected included that of medical history, physical examination, and periodic evaluation clinically, laboratory, and histopathologically during their follow up. Results: The mean age at diagnosis of HCV infection was 8 ± 3.3 years, the period of follow up of the patients in the hepatology clinic ranged from 0.3 to 15 years with a mean of 2.6 ± 2.3 years. Risk factors for HCV acquisition were chemotherapy in 93.5%, blood transfusions in 83.9%, and operations in 64.5%. Out of the 31 cases, 51.6% had leukemia. At first presentation, serum ALT level was elevated in 83.9% and AST level was elevated in 80.6%. Liver biopsy was performed in 26 cases; 96.1% had mild to moderate activity, 32% had no fibrosis, and 68% had mild to moderate fibrosis. Eighteen cases received HCV treatment. The response to HCV treatment was 27.7%. Although hepatitis C infection acquired by childhood cancer survivors was presented initially with high rate of elevated liver enzymes and PCR positivity, it seems to have a relatively benign clinical course with mild to moderate chronic hepatitis.
- [The relationship between calcaneus bone mineral density and metabolic syndrome]. [English Abstract, Journal Article]
- Zhonghua Nei Ke Za Zhi 2014 Jul; 53(7):542-5.
To evaluate the association between calcaneus bone mineral density (BMD) and metabolic syndrome (MS).A cross-sectional study was carried out in 5 552 subjects with 1 987 men and 3 565 women (age:40-87 years old). MS was defined according to Chinese Diabetes Society criteria. BMD was assessed by quantitative ultrasound.The proportion of MS was 29.0% in male and 24.4% in female. There were no differences in BMD between MS and non-MS subjects in both genders. Linear trend analysis displayed that BMD was positively associated with the increase of MS components in post-menopausal women after adjustment of age, ALT, creatinine and exercises (P < 0.05). Moreover, multiple regression analysis showed that BMD was inversely correlated with age (β = -0.034, P < 0.001) and positively correlated with BMI (β = 0.046, P = 0.001) , TG (β = 0.066, P = 0.034) and systolic blood pressure (SBP) (β = 0.007, P = 0.039) in post-menopausal women with MS.BMD tended to increase with the numbers of MS components in post-menopausal women. It was positively correlated with BMI, TG and SBP in postmenopausal women with MS.
- Three percent weight reduction is the minimum requirement to improve health hazards in obese and overweight people in Japan. [JOURNAL ARTICLE]
- Obes Res Clin Pract 2014 September - October; 8(5):e466-e475.
Adequate goal-setting is important in health counselling and treatment for obesity and overweight. We tried to determine the minimum weight reduction required for improvement of obesity-related risk factors and conditions in obese and overweight Japanese people, using a nationwide intervention programme database.Japanese men and women (n=3480; mean age±standard deviation [SD], 48.3±5.9 years; mean body mass index±SD, 27.7±2.5kgm(-2)) with "Obesity Disease" or "Metabolic Syndrome" participated in a 6-month lifestyle modification programme (specific health guidance) and underwent follow-up for 6 months thereafter. The relationship between percent weight reduction and changes in 11 parameters of obesity-related diseases were examined.Significant weight reduction was observed 6 months after the beginning of the programme, and it was maintained for 1 year. Concomitant improvements in parameters for obesity-related diseases were also observed. One-third of the subjects reduced their body weight by ≥3%. In the group exhibiting 1% to <3% weight reduction, plasma triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), haemoglobin A1c (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γ-GTP) decreased significantly, and high-density lipoprotein cholesterol (HDL-C) increased significantly compared to the control group (±1% weight change group). In addition to the improvements of these 7 parameters (out of 11), significant reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG) and uric acid (UA) (total 11 of 11 parameters) were observed in the group with 3% to <5% weight reduction. In the group with ≥5% weight reduction, the same 11 parameters also improved as those in the group with 3% to <5% weight reduction.The 6-month lifestyle modification programme induced significant weight reduction and significant improvement of parameters of obesity-related diseases. All the measured obesity-related parameters were significantly improved in groups with 3% to <5% and ≥5% weight reduction. Based on these findings, the minimum weight reduction required for improvement of obesity-related risk factors or conditions is 3% in obese and overweight (by WHO classification) Japanese people.
- Influence of Dietary Zinc on Semen Traits and Seminal Plasma Antioxidant Enzymes and Trace Minerals of Beetal Bucks. [JOURNAL ARTICLE]
- Reprod Domest Anim 2014 Sep 26.
Zinc (Zn) is a potent antioxidant and plays a key role in scavenging free radicals. We hypothesized that supplementation of Zn would reduce the oxidative damage, which is linked with poor sperm quality. Sixteen bucks of similar average age (2 years) and body weight (41 kg) were randomly divided into four groups viz., 1, 2, 3 and 4 supplemented with zinc sulphate into the diet at the rate of 0, 50, 100 and 200 mg/buck/day, respectively, for 3 months. At the end of the experiment, semen samples were collected and assessed. Seminal plasma was separated to find the concentration of superoxide dismutase (SOD), glutathione peroxidase (GPx), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and trace minerals (Zn, Cu, Mn and Fe). The results revealed that semen volume (1.85 ± 0.01 ml) and sperm motility (88.23 ± 5.77%) increased significantly (p < 0.05) in supplemented groups compared with the control specifically in group 3. SOD (10.66 ± 0.23 inhibition rate %) and GPx (23.55 ± 0.49 mU/ml) increased significantly (p < 0.05) in group 3 with no effect on AST and ALT. Among seminal plasma trace elements, no significant change (p > 0.05) was observed. From the present results, we concluded that zinc sulphate at the rate of 100 mg/buck/day improved semen traits and seminal plasma antioxidant capacity in Beetal bucks.