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Sample records for increased childhood liver

  1. Increased childhood liver cancer mortality and arsenic in drinking water in Northern Chile

    PubMed Central

    Liaw, Jane; Marshall, Guillermo; Yuan, Yan; Ferreccio, Catterina; Steinmaus, Craig; Smith, Allan H.

    2009-01-01

    Arsenic in drinking water is an established cause of lung, bladder and skin cancers in adults, and may also cause adult kidney and liver cancer. Some evidence for these effects originated from Region II of Chile which had a period of elevated arsenic levels in drinking water, in particular from 1958 to 1970. This unique exposure scenario provides a rare opportunity to investigate the effects of early-life arsenic exposure on childhood mortality; to our knowledge, this is the first study of childhood cancer mortality and high concentrations of arsenic in drinking water. In this paper, we compare cancer mortality rates under the age of 20 in Region II during 1950–2000 with those of unexposed Region V, dividing subjects into those born before, during or after the peak exposure period. Mortality from the most common childhood cancers, leukemia and brain cancer, were not increased in the exposed population. However, we found childhood liver cancer mortality occurred at higher rates than expected; for those exposed as young children liver cancer mortality between ages 0–19 was especially high: the relative risk (RR) for males born during this period was 8.9 (95% CI 1.7–45.8; p=0.009), for females the corresponding RR was 14.1 (95% CI 1.6–126; p=0.018), and for males and females pooled, the RR was 10.6 (95% CI 2.9–39.2; p<0.001). These findings suggest exposure to arsenic in drinking water during early childhood may result in an increase in childhood liver cancer mortality. PMID:18708388

  2. Increased childhood liver cancer mortality and arsenic in drinking water in northern Chile.

    PubMed

    Liaw, Jane; Marshall, Guillermo; Yuan, Yan; Ferreccio, Catterina; Steinmaus, Craig; Smith, Allan H

    2008-08-01

    Arsenic in drinking water is an established cause of lung, bladder, and skin cancers in adults and may also cause adult kidney and liver cancers. Some evidence for these effects originated from region II of Chile, which had a period of elevated arsenic levels in drinking water, in particular from 1958 to 1970. This unique exposure scenario provides a rare opportunity to investigate the effects of early-life arsenic exposure on childhood mortality; to our knowledge, this is the first study of childhood cancer mortality and high concentrations of arsenic in drinking water. In this article, we compare cancer mortality rates under the age of 20 in region II during 1950 to 2000 with those of unexposed region V, dividing subjects into those born before, during, or after the peak exposure period. Mortality from the most common childhood cancers, leukemia and brain cancer, was not increased in the exposed population. However, we found that childhood liver cancer mortality occurred at higher rates than expected. For those exposed as young children, liver cancer mortality between ages 0 and 19 was especially high: the relative risk (RR) for males born during this period was 8.9 [95% confidence interval (95% CI), 1.7-45.8; P = 0.009]; for females, the corresponding RR was 14.1 (95% CI, 1.6-126; P = 0.018); and for males and females pooled, the RR was 10.6 (95% CI, 2.9-39.2; P < 0.001). These findings suggest that exposure to arsenic in drinking water during early childhood may result in an increase in childhood liver cancer mortality.

  3. Non-alcoholic fatty liver disease and childhood obesity.

    PubMed

    Mathur, Prashant; Das, Manoja K; Arora, Narendra K

    2007-04-01

    Obesity has emerged as a significant global health problem in the pediatric population. Pediatric liver disease is a serious complication of childhood obesity. Non-alcoholic steatohepatitis (NASH) is an entity in the spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from fat in the liver--simple steatosis, NASH/ steatohepatitis--fat with in.ammation and/or fibrosis to advanced fibrosis and cirrhosis when fat may no longer be present. NASH is associated with obesity, diabetes, insulin resistance (IR), and hypertriglyceridemia. Children get NAFLD, and the incidence of this pediatric liver disease is rising as childhood obesity becomes increasingly prevalent. Although much remains to be learned about pediatric NAFLD, it is already evident that children with NASH risk progressive liver damage, including cirrhosis. Liver biopsy is required for definitive diagnosis, and other causes of fatty liver in childhood must be excluded. Gradual weight loss through increased regular exercise and a low-fat, low-refined carbohydrate diet appears to be effective. Drug treatments are being developed. The important message is that childhood obesity poses important health problems, including but not limited to potentially severe chronic liver disease. Early diagnosis of children who are only overweight is a worthy goal so that strategies to limit obesity can be instituted as early as possible. Identification of genetic risks is important, but management will invariably require changes in environmental factors. In addition to individual treatment, a multifaceted, societal initiative is required for solving the childhood obesity epidemic.

  4. [Childhood liver transplantation. Long-term results].

    PubMed

    Jara, Paloma; Hierro, Loreto

    2010-05-01

    Liver transplantation allows long-term survival (10 years or more) in 75% of children receiving transplants before 2000. The risk of mortality after the first year is 4-10% in the next 10-20 years. Chronic rejection affects 6%. The need for late retransplantation is 3-5%. However, the follow-up of these patients involves the management of diverse problems in the graft (immunological, biliary, vascular) and others related to the use of immunosuppressants (renal dysfunction, lymphoproliferative syndrome). The transition from pediatric to adult care generates special needs. Adolescence and young adulthood are associated with a lack of compliance. Adult specialists should be aware of the special features of the original diagnosis and the surgical techniques used in childhood transplantation. Final quality of life is good overall but is lower than that in healthy young persons.

  5. Increased coagulation in childhood obesity.

    PubMed

    Bilge, Yildiz Dallar; Alioglu, Bulent; Simşek, Enver; Tapci, Ayse Esra; Ozen, Cınar

    2012-11-01

    This study aims to explore the relation between childhood obesity and procoagulant and anticoagulant systems. Fifty-one obese children and 32 normal-weighted children with similar age and gender distribution and between ages of 5 and 16 years were recruited to the study. Antropometric measures of all subjects, existence of any accompanying disease, and medication histories had been recorded. Full blood count, procoagulant, and anticoagulant coagulation tests were run for all subjects. When hematologic variables of obese children were compared with those of healthy controls, it was found that average erythrocyte hemoglobin concentration, erythrocyte distribution width, and platelet count of obese children are significantly higher than healthy control group. It was also found that fibrinogen, thrombin time, factor (F) VIII, FIX, FX, and von Willebrand factor levels of obese children are higher than healthy control group. By contrast, antithrombin levels of obese children are found to be lower. In our study, we found that there is a procoagulant increase in the coagulation system activity of obese children compared to non-obese healthy children, whereas there is a significant decrease in anticoagulant system. These changes occurred in obese patients, especially higher levels of plasma procoagulant factors such as fibrinogen, FVIII, FIX, and von Willebrand factor, lead us to think that there is an activity in these patients at endothelial level. Further studies are needed on endothelial activity of obese children.

  6. Liver Abscess: Increasing Occurrence in Premature Newborns

    PubMed Central

    Bosnalı, Oktav; Moralıoğlu, Serdar; Pektaş, Osman

    2013-01-01

    Neonatal liver abscess is a very rare condition associated with high morbidity and mortality rates. There seems to be an increasing trend of this rare condition amongst the newborns admitted to neonatal intensive care units. We report a case of liver abscess in a premature newborn and briefly review the literature and discuss its management. PMID:26023443

  7. Arterial pressure suffices to increase liver stiffness.

    PubMed

    Piecha, Felix; Peccerella, Teresa; Bruckner, Tom; Seitz, Helmut-Karl; Rausch, Vanessa; Mueller, Sebastian

    2016-11-01

    Noninvasive measurement of liver stiffness (LS) has been established to screen for liver fibrosis. Since LS is also elevated in response to pressure-related conditions such as liver congestion, this study was undertaken to learn more about the role of arterial pressure on LS. LS was measured by transient elastography (μFibroscan platform, Echosens, Paris, France) during single intravenous injections of catecholamines in anesthetized rats with and without thioacetamide (TAA)-induced fibrosis. The effect of vasodilating glycerol trinitrate (GTN) on LS was also studied. Pressures in the abdominal aorta and caval and portal veins were measured in real time with the PowerLab device (AD Instruments, Dunedin, New Zealand). Baseline LS values in all rats (3.8 ± 0.5 kPa, n = 25) did not significantly differ from those in humans. Epinephrine and norepinephrine drastically increased mean arterial pressure (MAP) from 82 to 173 and 156 mmHg. Concomitantly, LS almost doubled from 4 to 8 kPa, while central venous pressure remained unchanged. Likewise, portal pressure only showed a slight and delayed increase. In the TAA-induced fibrosis model, LS increased from 9.5 ± 1.0 to 25.6 ± 14.7 kPa upon epinephrine injection and could efficiently be decreased by GTN. We finally show a direct association in humans in a physiological setting of elevated cardiac output and MAP. During continuous spinning at 200 W, MAP increased from 84 ± 8 to 99 ± 11 mmHg while LS significantly increased from 4.4 ± 1.8 to 6.7 ± 2.1 kPa. In conclusion, our data show that arterial pressure suffices to increase LS. Moreover, lowering MAP efficiently decreases LS in fibrotic livers that are predominantly supplied by arterial blood. Copyright © 2016 the American Physiological Society.

  8. Childhood Energy Intake Is Associated with Nonalcoholic Fatty Liver Disease in Adolescents123

    PubMed Central

    Anderson, Emma L; Howe, Laura D; Fraser, Abigail; Macdonald-Wallis, Corrie; Callaway, Mark P; Sattar, Naveed; Day, Chris; Tilling, Kate; Lawlor, Debbie A

    2015-01-01

    Background: Greater adiposity is an important risk factor for nonalcoholic fatty liver disease (NAFLD). Thus, it is likely that dietary intake is involved in the development of the disease. Prospective studies assessing the relation between childhood dietary intake and risk of NAFLD are lacking. Objective: This study was designed to explore associations between energy, carbohydrate, sugar, starch, protein, monounsaturated fat, polyunsaturated fat, saturated fat, and total fat intake by youth at ages 3, 7, and 13 y and subsequent (mean age: 17.8 y) ultrasound scan (USS)–measured liver fat and stiffness and serum alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase. We assessed whether observed associations were mediated through fat mass at the time of outcome assessment. Methods: Participants were from the Avon Longitudinal Study of Parents and Children. Trajectories of energy and macronutrient intake from ages 3–13 y were obtained with linear-spline multilevel models. Linear and logistic regression models examined whether energy intake and absolute and energy-adjusted macronutrient intake at ages 3, 7, and 13 y were associated with liver outcomes. Results: Energy intake at all ages was positively associated with liver outcomes; for example, the odds of having a USS-measured liver fat per 100 kcal increase in energy intake at age 3 y were 1.79 (95% CI: 1.14, 2.79). Associations between absolute macronutrient intake and liver outcomes were inconsistent and attenuated to the null after adjustment for total energy intake. The majority of associations attenuated to the null after adjustment for fat mass at the time liver outcomes were assessed. Conclusion: Higher childhood and early adolescent energy intake is associated with greater NAFLD risk, and the macronutrients from which energy intake is derived are less important. These associations appear to be mediated, at least in part, by fat mass at the time of outcome assessment. PMID

  9. Metabolic syndrome in childhood from impaired carbohydrate metabolism to nonalcoholic fatty liver disease.

    PubMed

    Manco, Melania

    2011-10-01

    Compelling evidence supports the concept that nonalcoholic fatty liver disease (NAFLD) represents the hepatic component of metabolic syndrome (MetS). Intrahepatic fat seems to predict more strongly than does visceral adiposity an individual's cardiovascular risk and the likelihood that metabolic abnormalities are present in youth. Young individuals with fatty liver are more insulin resistant and present with a higher prevalence of metabolic abnormalities than do individuals without intrahepatic fat accumulation. They also present with a certain endothelial dysfunction and greater carotid intima-media thickness. Conversely, youth with MetS seem to have an increased risk of developing liver inflammation, a condition termed nonalcoholic steatohepatitis (NASH), and fibrosis. In the context of MetS, the liver is central in that it can drive both hepatic and systemic insulin resistance, trigger low-grade inflammation, and promote atherogenic processes. In the context of MetS, NAFLD and altered carbohydrate metabolism track from childhood to adulthood. Thus, prevention, recognition, and effective treatment of these two abnormalities may limit the burden of morbidity and mortality associated with obesity and may delay onset of cardiovascular disease in early adulthood. The present review aims at systematically presenting evidence of the critical interplay of fatty liver and altered glucose metabolism in youth. It attempts to provide pathogenetic explanations for such an association and the rationale for its treatment, with particular regard to nutritional interventions. Key teaching points: Overweight and obese youth should be screened for fatty liver disease once after puberty by liver function tests and ultrasonography. Screening for fatty liver should be accurately performed in young patients with features of metabolic syndrome. Obese patients with fatty liver are at increased risk for altered glucose metabolism, thus they should undergo an oral glucose tolerance test

  10. Gastrointestinal and liver lesions in primary childhood Sjögren syndrome.

    PubMed

    Kashiwagi, Yasuyo; Hatsushika, Tatsuro; Tsutsumi, Norito; Go, Soken; Nishimata, Shigeo; Kawashima, Hisashi

    2017-06-01

    Sjögren syndrome (SS) is characterized by lymphocytic infiltration of exocrine glands, mainly the lacrimal and salivary glands, leading to keratoconjunctivitis sicca and xerostomia. SS is one of the most common autoimmune rheumatic diseases in adults; however, few cases of primary childhood SS with gastrointestinal and liver lesions have been reported in the literature. We report five cases of primary childhood SS with gastrointestinal and liver lesions. Multiple gastric biopsies in four cases revealed atrophic gastritis in the antrum of the stomach or chronic gastritis. Liver biopsies in two cases revealed nonalcoholic steatohepatitis. Careful clinical approach and follow-up for gastrointestinal and liver lesions are required.

  11. Increased Synthesis of Liver Erythropoietin with CKD.

    PubMed

    de Seigneux, Sophie; Lundby, Anne-Kristine Meinild; Berchtold, Lena; Berg, Anders H; Saudan, Patrick; Lundby, Carsten

    2016-08-01

    Anemia of CKD seems to be related to impaired production of renal erythropoietin (Epo). The glycosylation pattern of Epo depends on the synthesizing cell and thus, can indicate its origin. We hypothesized that synthesis of Epo from nonkidney cells increases to compensate for insufficient renal Epo production during CKD. We determined plasma Epo levels and Epo glycosylation patterns in 33 patients with CKD before undergoing dialysis and nine patients with CKD undergoing dialysis. We compared these values with values obtained in healthy volunteers and other controls. Although patients with CKD before undergoing dialysis had median (interquartile range) Epo levels higher than those of healthy controls (13.8 IU/L; interquartile range, 10.0-20.7 IU/L versus 8.4 IU/L; interquartile range, 7.6-9.0 IU/L; P<0.01), these patients were moderately anemic (mean±SD; hemoglobin =118±17 g/L). Detected as the percentage of migrated isoforms (PMI), Epo glycosylation in patients with CKD before undergoing dialysis (PMI=36.1±11.7%) differed from that in healthy controls (PMI=9.2±3.8%; P<0.01) but not from that in umbilical cord plasma (PMI=53.9±10.6%; P>0.05), which contains mainly liver-derived Epo. Furthermore, glycosylation modification correlated with eGFR loss. These results suggest that patients with CKD maintain persistent Epo synthesis despite declining renal function, and this maintenance may result in part from increased liver Epo synthesis.

  12. Long-term effect of childhood liver transplantation on body cell mass.

    PubMed

    Ee, Looi Cheng; Hill, Rebecca Joanne; Beale, Kerrie; Noble, Charlton; Fawcett, Jonathan; Cleghorn, Geoffrey John

    2014-08-01

    Malnutrition is common in end-stage liver disease, but a correction after transplantation is expected. Body cell mass (BCM) assessment using total body potassium (TBK) measurements is considered the gold standard for assessing nutritional status. The aim of this study was to examine the BCM and, therefore, nutritional status of long-term survivors after childhood liver transplantation. This was a longitudinal nested cohort study of patients undergoing transplantation at <18 years of age and surviving >3 years with ongoing review at our center. TBK measurements were obtained before transplantation and during long-term follow-up. BCM was calculated from TBK and was adjusted for the height raised to power p, which depended on sex (BCM/height(p)). The effects of the age at transplant, linear growth impairment, a diagnosis of biliary atresia, and steroid use were assessed. Thirty-two patients (20 males) participated; 59% had biliary atresia. The median age at transplant was 2.11 years (range = 0.38-10.92 years). Posttransplant testing was performed at a median of 7.23 years (range = 3.28-14.99 years) when they were 10.12 years old (range = 4.56-20.77 years). This cohort attained mean z scores for height, weight, and body mass index of -0.41 ± 1.36, -0.26 ± 1.14, and 0.04 ± 0.99, respectively. BCM/height(p) was reduced before transplantation but was further reduced after transplantation (P < 0.001) despite the normalization of height and weight. Weight recovery, therefore, likely came from increased fat mass and not BCM. Linear growth impairment was associated with a greater reduction in posttransplant BCM/height(p) (P = 0.02). In multivariate analyses, only an older age at transplant predicted reduced posttransplant BCM/height(p) (P = 0.02). The age at transplant, sex, steroid use, and underlying diagnosis did not predict changes in BCM/height(p) after transplantation. In conclusion, weight recovery in long-term survivors of childhood liver transplantation is likely

  13. Candidiasis of the liver and spleen in childhood

    SciTech Connect

    Miller, J.H.; Greenfield, L.D.; Wald, B.R.

    1982-02-01

    Four children with acute leukemia and surgically documented candidiasis of the liver and/or spleen were examined with a combination of diagnostic imaging modalities including /sup 99m/Tc-sulfur colloid and /sup 67/Ga- citrate scintigraphy, gray-scale ultrasound, and body computed tomography (CT). Abnormalities were detected in every individual examined. /sup 99m/Tc-sulfur colloid scintigraphy revealed ''cold'' areas in the liver or spleen. With /sup 67/Ga scintigraphy, these areas were ''cold'' in some individuals and ''hot'' in others. Gray-scale ultrasound demonstrated hypoechoic lesions with central areas of increased echogenicity in hepatic involvement, and hypoechoic replacement of the spleen in splenic involvement. CT in one patient revealed low-density areas without contrast enhancement within the hepatic parenchyma and unsuspected renal involvement.

  14. Candidiasis of the liver and spleen in childhood

    SciTech Connect

    Miller, J.H.; Greenfield, L.D.; Wald, B.R.

    1982-02-01

    Four children with acute leukemia and surgically documented candidiasis of the liver and/or spleen were examined with a combination of diagnostic imaging modalities including /sup 99/mTc-sulfur colloid and /sup 67/Ga-citrate scintigraphy, gray-scale ultrasound, and body computed tomography (CT). Abnormalities were detected in every individual examined. /sup 99/mTc-sulfur colloid scintigraphy revealed cold areas in the liver or spleen. With /sup 67/Ga scintigraphy, these areas were cold in some individuals and hot in others. Gray-scale ultrasound demonstrated hypoechoic lesions with central areas of increased echogenicity in hepatic involvement, and hypoechoic replacement of the spleen in splenic involvement. CT in one patient revealed low-density areas without contrast enhancement within the hepatic parenchyma and unsuspected renal involvement.

  15. Non-alcoholic fatty liver disease is associated with early left ventricular dysfunction in childhood acute lymphoblastic leukaemia survivors.

    PubMed

    Delvecchio, Maurizio; Muggeo, Paola; Monteduro, Mariantonietta; Lassandro, Giuseppe; Novielli, Chiara; Valente, Federica; Salinaro, Emanuela; Zito, Annapaola; Ciccone, Marco Matteo; Miniello, Vito Leonardo; Santoro, Nicola; Giordano, Paola; Faienza, Maria Felicia

    2017-02-01

    Childhood acute lymphoblastic leukaemia (ALL) survivors have an increased risk of metabolic and cardiovascular disease. We aimed to assess the presence of non-alcoholic fatty liver disease (NAFLD) in childhood ALL and if it is associated with early cardiovascular dysfunction. In total, 53 childhood ALL survivors and 34 controls underwent auxological evaluation, biochemical assay, liver, heart and vascular ultrasound study. NAFLD was more frequent in ALL patients than in controls (39.6% vs 11.7%, P < 0.01). Patients with NAFLD were more obese and insulin resistant than patients without NAFLD. Flow-mediated dilatation and interventricular septum were lower in the ALL group than those in the control group (P < 0.001 for both). The patients with NAFLD showed lower left ventricular ejection fraction than those without NAFLD (P = 0.011). In ALL survivors, BMI-SDS and subcutaneous fat were the strongest predictors of NAFLD, whereas preperitoneal adipose tissue and C-reactive protein were the strongest predictors of left ventricular ejection fraction. Childhood ALL survivors had higher prevalence of NAFLD than healthy controls, which is associated with early left ventricular impairment. In the case of fatty liver, a comprehensive heart evaluation is mandatory. We strongly recommend to prevent visceral adiposity in ALL survivors, to search for metabolic syndrome or its components and to reinforce the need of intervention on diet and lifestyle during the follow-up of these patients. © 2017 European Society of Endocrinology.

  16. ADOPTION OF MELD SCORE INCREASES THE NUMBER OF LIVER TRANSPLANT

    PubMed Central

    NACIF, Lucas Souto; ANDRAUS, Wellington; MARTINO, Rodrigo Bronze; SANTOS, Vinicius Rocha; PINHEIRO, Rafael Soares; HADDAD, Luciana BP; D'ALBUQUERQUE, Luiz Carneiro

    2014-01-01

    Background Liver transplantation is performed at large transplant centers worldwide as a therapeutic intervention for patients with end-stage liver diseases. Aim To analyze the outcomes and incidence of liver transplantation performed at the University of São Paulo and to compare those with the State of São Paulo before and after adoption of the Model for End-Stage Liver Disease (MELD) score. Method Evaluation of the number of liver transplantations before and after adoption of the MELD score. Mean values and standard deviations were used to analyze normally distributed variables. The incidence results were compared with those of the State of São Paulo. Results There was a high prevalence of male patients, with a predominance of middle-aged. The main indication for liver transplantation was hepatitis C cirrhosis. The mean and median survival rates and overall survival over ten and five years were similar between the groups (p>0.05). The MELD score increased over the course of the study period for patients who underwent liver transplantation (p>0.05). There were an increased number of liver transplants after adoption of the MELD score at this institution and in the State of São Paulo (p<0.001). Conclusion The adoption of the MELD score led to increase the number of liver transplants performed in São Paulo. PMID:25184772

  17. Childhood abuse is associated with increased startle reactivity in adulthood.

    PubMed

    Jovanovic, Tanja; Blanding, Nineequa Q; Norrholm, Seth D; Duncan, Erica; Bradley, Bekh; Ressler, Kerry J

    2009-01-01

    Understanding the neurobiological correlates of childhood maltreatment is critical to delineating stress-related psychopathology. The acoustic startle response (ASR) is a subcortical reflex modulated by neural systems implicated in posttraumatic stress disorder (PTSD). The ASR is conserved across species and is increased in rodent models of developmental stress. We measured ASR to a 40 ms noise probe as well as fear-potentiated startle using electromyographic recordings of the eyeblink in a primarily African American sample (N=60) from a highly traumatized civilian population. We assessed self-reported history of abuse with the Childhood Trauma Questionnaire and current symptoms with the PTSD Symptom Scale and the Beck Depression Inventory. We found that subjects reporting a history of high levels of physical or sexual abuse had increased startle on all trial types relative to those with low abuse (P<.01). This effect remained significant after co-varying for the subjects' age and sex, as well as PTSD and depression symptoms. Perceived childhood sexual abuse was the greatest predictor of increased startle response. Notably, emotional abuse in childhood did not affect baseline startle, and all groups demonstrated equivalent levels of fear-potentiated startle. The long-lasting effects of early life trauma result in increased risk for adult psychopathology. These new data demonstrate that a self-report history of child abuse is related to altered baseline startle response that is not accounted for by PTSD or depression symptoms. Increased startle may be a biomarker of stress responsiveness that can be a persevering consequence of early trauma exposure during childhood.

  18. Assessment of biochemical liver markers, physical activity, fitness and body mass index for a cardiometabolic risk model in childhood.

    PubMed

    Konidari, A; Auth, M K H; Murphy, M H; Cunningham, C; Foweather, L; Gobbi, R; Graves, L E F; Hopkins, N D; Stratton, G; Boddy, L M

    2014-05-01

    The aim of this study was to investigate clustered cardiometabolic risk scores in healthy 10- to 12-year-olds using anthropometric characteristics, measurements of cardiorespiratory fitness (CRF) and physical activity and blood markers of metabolic disease. We also evaluated how including markers of liver cell injury would affect the clustered cardiometabolic risk assessment model. This cross-sectional study focused on 99 children aged 10-12 years. The main outcome included assessing participants with increased and low cardiometabolic risk factors using a clustered risk score model that incorporated markers implicated in metabolic syndrome pathogenesis. Two clustered risk scores were calculated, one incorporating markers of liver cell injury. Children classified as 'increased risk' exhibited significantly lower CRF and higher body mass index Z-scores than their 'low-risk' peers. No significant differences in physical activity were observed. This trend remained unchanged when markers of liver injury were included in the clustered risk assessment model. The clustered risk score model is a scientifically robust method of cardiometabolic risk assessment, which reiterates the importance of weight reduction and CRF promotion in childhood. Our study did not show a significant contribution of liver injury markers, and further research is needed to evaluate their effect on cardiometabolic risk stratification in childhood. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  19. Dietary sugar intake increases liver tumor incidence in female mice

    PubMed Central

    Healy, Marin E.; Lahiri, Sujoy; Hargett, Stefan R.; Chow, Jenny D.Y.; Byrne, Frances L.; Breen, David S.; Kenwood, Brandon M.; Taddeo, Evan P.; Lackner, Carolin; Caldwell, Stephen H.; Hoehn, Kyle L.

    2016-01-01

    Overnutrition can promote liver cancer in mice and humans that have liver damage caused by alcohol, viruses, or carcinogens. However, the mechanism linking diet to increased liver tumorigenesis remains unclear in the context of whether tumorigenesis is secondary to obesity, or whether nutrients like sugar or fat drive tumorigenesis independent of obesity. In male mice, liver tumor burden was recently found to correlate with sugar intake, independent of dietary fat intake and obesity. However, females are less susceptible to developing liver cancer than males, and it remains unclear how nutrition affects tumorigenesis in females. Herein, female mice were exposed to the liver carcinogen diethylnitrosamine (DEN) and fed diets with well-defined sugar and fat content. Mice fed diets with high sugar content had the greatest liver tumor incidence while dietary fat intake was not associated with tumorigenesis. Diet-induced postprandial hyperglycemia and fasting hyperinsulinemia significantly correlated with tumor incidence, while tumor incidence was not associated with obesity and obesity-related disorders including liver steatosis, glucose intolerance, or elevated serum levels of estrogen, ALT, and lipids. These results simplify the pathophysiology of diet-induced liver tumorigenesis by focusing attention on the role of sugar metabolism and reducing emphasis on the complex milieu associated with obesity. PMID:26924712

  20. Dietary sugar intake increases liver tumor incidence in female mice.

    PubMed

    Healy, Marin E; Lahiri, Sujoy; Hargett, Stefan R; Chow, Jenny D Y; Byrne, Frances L; Breen, David S; Kenwood, Brandon M; Taddeo, Evan P; Lackner, Carolin; Caldwell, Stephen H; Hoehn, Kyle L

    2016-02-29

    Overnutrition can promote liver cancer in mice and humans that have liver damage caused by alcohol, viruses, or carcinogens. However, the mechanism linking diet to increased liver tumorigenesis remains unclear in the context of whether tumorigenesis is secondary to obesity, or whether nutrients like sugar or fat drive tumorigenesis independent of obesity. In male mice, liver tumor burden was recently found to correlate with sugar intake, independent of dietary fat intake and obesity. However, females are less susceptible to developing liver cancer than males, and it remains unclear how nutrition affects tumorigenesis in females. Herein, female mice were exposed to the liver carcinogen diethylnitrosamine (DEN) and fed diets with well-defined sugar and fat content. Mice fed diets with high sugar content had the greatest liver tumor incidence while dietary fat intake was not associated with tumorigenesis. Diet-induced postprandial hyperglycemia and fasting hyperinsulinemia significantly correlated with tumor incidence, while tumor incidence was not associated with obesity and obesity-related disorders including liver steatosis, glucose intolerance, or elevated serum levels of estrogen, ALT, and lipids. These results simplify the pathophysiology of diet-induced liver tumorigenesis by focusing attention on the role of sugar metabolism and reducing emphasis on the complex milieu associated with obesity.

  1. Investigating a Liver Fat: Arterial Stiffening Pathway in Adult and Childhood Obesity.

    PubMed

    Rider, Oliver J; Banerjee, Rajarshi; Rayner, Jennifer J; Shah, Ravi; Murthy, Venkatesh L; Robson, Matthew D; Neubauer, Stefan

    2016-01-01

    To investigate the relationship between hepatic fat content, circulating triglyceride levels and aortic stiffness in adult and childhood obesity. Seventy-seven adults and 18 children across a wide range of body mass index (18.5-52.6 kg/m(2); percentile 8-100) with no identifiable cardiac risk factors underwent; 1H- magnetic resonance spectroscopy to quantify hepatic fat content and magnetic resonance imaging to assess aortic pulse wave velocity (PWV) and regional distensibility. In adults, multivariable regression showed age (β=0.09; P=0.02), liver fat (β=2.5; P=0.04), and serum triglyceride (β=0.47; P=0.01) to be independent predictors of PWV. Age and blood pressure-adjusted, moderated regression showed that 43% of the total negative effect of hepatic fat on PWV is attributable to indirect effects via increased triglyceride (P=0.005). In addition, regional distensibility was positively correlated with hepatic fat (ascending; r=-0.35; descending, r=-0.23; abdominal, r=-0.41; all P<0.001). Similar to that seen in adults, PWV (r=0.72; P<0.001) and abdominal regional distensibility (r=-0.52; P<0.001) were correlated with liver fat in children. Increasing age, liver fat, and triglyceride are all related to increased aortic stiffness in adults. Even when controlling for the effects of age and blood pressure, hepatic fat has a negative effect on PWV, with substantial indirect effect occurring via increased circulating triglyceride level. This relationship between hepatic fat and aortic stiffness occurs early in the obesity process and is also seen in children. As such, hepatic fat content is a potential therapeutic target to treat the elevated vascular risk in obesity. © 2015 American Heart Association, Inc.

  2. Increased sinusoidal volume and solute extraction during retrograde liver perfusion

    SciTech Connect

    Bass, N.M.; Manning, J.A.; Weisiger, R.A.

    1989-06-01

    Retrograde isolated liver perfusion has been used to probe acinar functional heterogeneity, but the hemodynamic effects of backward flow have not been characterized. In this study, extraction of a long-chain fatty acid derivative, 12-N-methyl-7-nitrobenzo-2-oxa-1,3-diazol-amino stearate (12-NBDS), was greater during retrograde than during anterograde perfusion of isolated rat liver. To determine whether hemodynamic differences between anterograde and retrograde perfused livers could account for this finding, the hepatic extracellular space was measured for both directions of flow by means of (/sup 14/C)sucrose washout during perfusion as well as by direct measurement of (/sup 14/C)sucrose entrapped during perfusion. A three- to fourfold enlargement of the total hepatic extracellular space was found during retrograde perfusion by both approaches. Examination of perfusion-fixed livers by light microscopy and morphometry revealed that marked distension of the sinusoids occurred during retrograde perfusion and that this accounts for the observed increase in the (/sup 14/C)sucrose space. These findings support the hypothesis that maximum resistance to perfusate flow in the isolated perfused rat liver is located at the presinusoidal level. In addition, increased transit time of perfusate through the liver and greater sinusoidal surface area resulting from sinusoidal distension may account for the higher extraction of 12-NBDS and possibly other compounds by retrograde perfused liver.

  3. Zolpidem Use Associated With Increased Risk of Pyogenic Liver Abscess

    PubMed Central

    Liao, Kuan-Fu; Lin, Cheng-Li; Lai, Shih-Wei; Chen, Wen-Chi

    2015-01-01

    Abstract The purpose of this study was to explore the association between zolpidem use and pyogenic liver abscess in Taiwan. This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. We identified 1325 patients aged 20 to 84 years with the first-attack of pyogenic liver abscess as the cases, and 5082 patients without pyogenic liver abscess matched with sex, age, comorbidities, and index year of hospitalization for pyogenic liver abscess as the controls. Patients whose last remaining 1 tablet for zolpidem was noted ≤7 days before the date of admission for pyogenic liver abscess were defined as current use of zolpidem. Patients whose last remaining 1 tablet for zolpidem was noted >7 days before the date of admission for pyogenic liver abscess were defined as late use of zolpidem. Patients who never received 1 prescription for zolpidem were defined as never use of zolpidem. A multivariable unconditional logistic regression model was used to measure the odds ratio (OR) and 95% confidence interval (CI) to explore the association between zolpidem use and pyogenic liver abscess. After adjustment for possible confounding variables, the adjusted OR of pyogenic liver abscess was 3.89 for patients with current use of zolpidem (95% CI 2.89, 5.23), when compared with those with never use of zolpidem. The adjusted OR decreased to 0.85 for those with late use of zolpidem (95% CI 0.70, 1.03), but without statistical significance. Current use of zolpidem is associated with the increased risk of pyogenic liver abscess. Physicians should take the risk of pyogenic liver abscess into account when prescribing zolpidem. PMID:26266369

  4. Increasing childhood influenza vaccination: a cluster randomized trial.

    PubMed

    Nowalk, Mary Patricia; Lin, Chyongchiou Jeng; Hannibal, Kristin; Reis, Evelyn C; Gallik, Gregory; Moehling, Krissy K; Huang, Hsin-Hui; Allred, Norma J; Wolfson, David H; Zimmerman, Richard K

    2014-10-01

    Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%. To evaluate an intervention to increase childhood influenza vaccination across age and racial groups. In 2011-2012, a total of 20 primary care practices treating children were randomly assigned to the intervention and control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity. The average vaccination differences from pre-intervention to the intervention year were significantly larger in the intervention arm (n=10 practices) than the control arm (n=10 practices); for children aged 9-18 years (11.1 pct pts intervention vs 4.3 pct pts control, p<0.05); for non-white children (16.7 pct pts intervention vs 4.6 pct pts control, p<0.001); and overall (9.9 pct pts intervention vs 4.2 pct pts control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race, and intervention, the likelihood of vaccination increased with younger age group (6-23 months); white race; commercial insurance; the practice's pre-intervention vaccination rate; and being in the intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9-18 years. A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza vaccination uptake across age and racial groups without targeting specific groups, especially in practices with large

  5. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

    PubMed Central

    Temple, Jonathan L.; Cordero, Paul; Li, Jiawei; Nguyen, Vi; Oben, Jude A.

    2016-01-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention. PMID:27314342

  6. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence.

    PubMed

    Temple, Jonathan L; Cordero, Paul; Li, Jiawei; Nguyen, Vi; Oben, Jude A

    2016-06-15

    Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%-20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, "paediatric" NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention.

  7. Increasing relational memory in childhood with unitization strategies.

    PubMed

    Robey, Alison; Riggins, Tracy

    2017-08-28

    Young children often experience relational memory failures, which are thought to result from immaturity of the recollection processes presumed to be required for these tasks. However, research in adults has suggested that relational memory tasks can be accomplished using familiarity, a process thought to be mature by the end of early childhood. The goal of the present study was to determine whether relational memory performance could be improved in childhood by teaching young children memory strategies that have been shown to increase the contribution of familiarity in adults (i.e., unitization). Groups of 6- and 8-year-old children were taught to use visualization strategies that either unitized or did not unitize pictures and colored borders. Estimates of familiarity and recollection were extracted by fitting receiver operator characteristic curves (Yonelinas, Journal of Experimental Psychology: Learning, Memory, and Cognition 20, 1341-1354, 1994, Yonelinas, Memory & Cognition 25, 747-763, 1997) based on dual-process models of recognition. Bayesian analysis revealed that strategies involving unitization improved memory performance and increased the contribution of familiarity in both age groups.

  8. Chronic exercise increases insulin binding in muscles but not liver

    SciTech Connect

    Bonen, A.; Clune, P.A.; Tan, M.H.

    1986-08-01

    It has been postulated that the improved glucose tolerance provoked by chronic exercise is primarily attributable to increased insulin binding in skeletal muscle. Therefore, the authors investigated the effects of progressively increased training (6 wk) on insulin binding by five hindlimb skeletal muscles and in liver. In the trained animals serum insulin levels at rest were lower either in a fed or fasted state and after an oral glucose tolerance test. Twenty-four hours after the last exercise bout sections of the liver, soleus (S), plantaris (P), extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG) muscles were pooled from four to six rats. Insulin binding to plasma membranes increased in S, P, and EDL but not in WG or in liver. There were insulin binding differences among muscles. Comparison of rank orders of insulin binding data with published glucose transport data for the same muscles revealed that these parameters do not correspond well. In conclusion, insulin binding to muscle is shown to be heterogeneous and training can increase insulin binding to selected muscles but not liver.

  9. Childhood Maltreatment Increases the Risk for Visceral Obesity

    PubMed Central

    Li, Li; Chassan, Rachel A.; Bruer, Emily H.; Gower, Barbara A.; Shelton, Richard C.

    2015-01-01

    Objective Reports regarding the associations between childhood maltreatment (CM) and body fat composition remain heterogeneous in humans although it is indicated in preclinical studies. Moreover, the effects of CM subtypes on different types of body fat are unclear. Thus this study is to determine the associations between CM and its subtypes with body fat and to explore the potential pathways. Methods Participants were assessed for a history of CM by the Childhood Trauma Questionnaire, and were divided into the CM group (with CM exposures) and non-CM group (without CM exposures). Body composition was measured by dual-energy X-ray absorptiometry. Subjects provided salivary and blood samples. Results Compared with the non-CM group, CM subjects had greater visceral fat mass (1136±160g vs. 836±116g, p<0.05) but not total body fat, android fat, body mass index or waist-to-hip ratio. Moreover, CM subjects had a blunted cortisol awakening response and elevated inflammatory factors. Correlation analysis indicated that CM subtypes had differential effects on visceral adiposity and cortisol awakening response. Conclusions Our results suggest that CM exposure is linked with increased visceral fat deposition, and the perturbation of the HPA axis activity and activation of the immune system may be 2 potential pathways that explain this relationship. PMID:26146933

  10. Familial Mediterranean Fever -- an increasingly important childhood disease in Sweden.

    PubMed

    Wekell, P; Friman, V; Balci-Peynircioglu, B; Yilmaz, E; Fasth, A; Berg, S

    2013-02-01

    To characterize Familial Mediterranean Fever (FMF) in western Sweden, focusing on genotype, clinical picture, prevalence and age of onset as well as time to diagnosis. Patients with autoinflammatory diseases are continuously registered at the five main hospitals in Western Sweden. Case records of patients with FMF were analysed retrospectively. Population data on immigration was retrieved from Statistics Sweden. Until 2008, 37 patients with FMF were identified. The prevalence among inhabitants of Turkish, Lebanese, Syrian and Iranian origin was 173, 124, 86 and 17/100 000, respectively. Median age at first symptoms was 4 years (range 3 month-37 years) and at diagnosis 10 years (range 2-44 years). Median time from first symptoms to diagnosis was 4 years (range <1 year-34 years). Among 32 patients screened for twelve common mutations, 75% were homozygotes or compound heterozygotes, 16% were heterozygotes and in 9% no mutation was found. In our cohort the frequencies of symptoms were fever 100%, peritonitis 92%, pleuritis 22% and arthritis 11%. The majority of patients with FMF present during childhood. The prevalence among immigrants in western Sweden is in the same range as in their country of origin. Time to diagnosis needs to be shortened by means of increased awareness of the disease. ©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.

  11. Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions.

    PubMed

    Alvarez, Daniel; Orozco, Federico; Mella, José María; Anders, Maria; Antinucci, Florencia; Mastai, Ricardo

    2015-01-01

    The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. We evaluated the effect of food intake on LS in patients with different degrees of liver disease. We evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. Food intake increased PBF (51±10%, p<0.001). Splanchnic hyperemia was accompanied by a significant rise in LS (from 7.8±3.3 to 10.3±4.1kPa, p<0.001). These increases were similar in patients with minimal fibrosis(F≤1) and in those with more advanced fibrosis or cirrhosis (F>1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  12. Childhood Conduct Problems Are Associated with Increased Partnership and Parenting Difficulties in Adulthood

    ERIC Educational Resources Information Center

    Raudino, Alessandra; Woodward, Lianne J.; Fergusson, David M.; Horwood, L. John

    2012-01-01

    This paper uses data from a sample of 337 parents studied at age 30 to examine the linkages between childhood conduct problems assessed at ages 7-9 and later partnership and parenting outcomes. The key findings of this study were: 1) increasing levels of childhood conduct problems were associated with increased risk of partnership difficulties,…

  13. Childhood Conduct Problems Are Associated with Increased Partnership and Parenting Difficulties in Adulthood

    ERIC Educational Resources Information Center

    Raudino, Alessandra; Woodward, Lianne J.; Fergusson, David M.; Horwood, L. John

    2012-01-01

    This paper uses data from a sample of 337 parents studied at age 30 to examine the linkages between childhood conduct problems assessed at ages 7-9 and later partnership and parenting outcomes. The key findings of this study were: 1) increasing levels of childhood conduct problems were associated with increased risk of partnership difficulties,…

  14. Variability and rapid increase in body mass index during childhood are associated with adult obesity.

    PubMed

    Li, Shengxu; Chen, Wei; Sun, Dianjianyi; Fernandez, Camilo; Li, Jian; Kelly, Tanika; He, Jiang; Krousel-Wood, Marie; Whelton, Paul K

    2015-12-01

    Body mass index (BMI) in childhood predicts obesity in adults, but it is unknown whether rapid increase and variability in BMI during childhood are independent predictors of adult obesity. The study cohort consisted of 1622 Bogalusa Heart Study participants (aged 20 to 51 years at follow-up) who had been screened at least four times during childhood (aged 4-19 years). BMI rate of change during childhood for each individual was assessed by mixed models; BMI residual standard deviation (RSD) during childhoodwas used as a measure of variability. The average follow-up period was 20.9 years. One standard deviation increase in rate of change in BMI during childhood was associated with 1.39 [95% confidence interval (CI): 1.17-1.61] kg/m(2) increase in adult BMI and 2.98 (95% CI: 2.42-3.56) cm increase in adult waist circumference, independently of childhood mean BMI. Similarly, one standard deviation increase in RSD in BMI during childhood was associated with 0.46 (95% CI: 0.23-0.69) kg/m(2) increase in adult BMI and 1.42 (95% CI: 0.82-2.02) cm increase in adult waist circumference. Odds ratio for adult obesity progressively increased from the lowest to the highest quartile of BMI rate of change or RSD during childhood (P for trend < 0.05 for both). Rapid increase and greater variability in BMI during childhood appear to be independent risk factors for adult obesity. Our findings have implications for understanding body weight regulation and obesity development from childhood to adulthood. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

  15. Variability and rapid increase in body mass index during childhood are associated with adult obesity

    PubMed Central

    Li, Shengxu; Chen, Wei; Sun, Dianjianyi; Fernandez, Camilo; Li, Jian; Kelly, Tanika; He, Jiang; Krousel-Wood, Marie; Whelton, Paul K

    2015-01-01

    Background: Body mass index (BMI) in childhood predicts obesity in adults, but it is unknown whether rapid increase and variability in BMI during childhood are independent predictors of adult obesity. Methods: The study cohort consisted of 1622 Bogalusa Heart Study participants (aged 20 to 51 years at follow-up) who had been screened at least four times during childhood (aged 4–19 years). BMI rate of change during childhood for each individual was assessed by mixed models; BMI residual standard deviation (RSD) during childhoodwas used as a measure of variability. The average follow-up period was 20.9 years. Results: One standard deviation increase in rate of change in BMI during childhood was associated with 1.39 [95% confidence interval (CI): 1.17–1.61] kg/m2 increase in adult BMI and 2.98 (95% CI: 2.42–3.56) cm increase in adult waist circumference, independently of childhood mean BMI. Similarly, one standard deviation increase in RSD in BMI during childhood was associated with 0.46 (95% CI: 0.23–0.69) kg/m2 increase in adult BMI and 1.42 (95% CI: 0.82–2.02) cm increase in adult waist circumference. Odds ratio for adult obesity progressively increased from the lowest to the highest quartile of BMI rate of change or RSD during childhood (P for trend < 0.05 for both). Conclusions: Rapid increase and greater variability in BMI during childhood appear to be independent risk factors for adult obesity. Our findings have implications for understanding body weight regulation and obesity development from childhood to adulthood. PMID:26452389

  16. Nonalcoholic fatty liver disease increases risk for gastroesophageal reflux symptoms.

    PubMed

    Catanzaro, Roberto; Calabrese, Federica; Occhipinti, Sergio; Anzalone, Maria Grazia; Italia, Angelo; Milazzo, Michele; Marotta, Francesco

    2014-08-01

    Nonalcoholic fatty liver disease (NAFLD) is now recognized as a leading cause of liver dysfunction. Gastroesophageal reflux disease (GERD) is a common disorder causing symptoms that often impair patients' quality of life. In recent years, the prevalence of both these diseases has increased, partially overlapping the rise of metabolic disorders. We investigated whether a relation does exist between NAFLD and GERD symptoms. Cross-sectional study among 206 outpatients diagnosed with NAFLD and 183 controls. We collected clinical and laboratory data, assessed severity and frequency of GERD symptoms and the esophageal endoscopic pattern. The prevalence of GERD symptoms was higher in NAFLD patients than controls (61.2 vs. 27.9%, p < 0.001). We found a positive association between NAFLD and the experiencing of heartburn, regurgitation and belching. GERD symptoms were related to body mass index (BMI) and metabolic syndrome (MetS); a strong association persisted after adjustment for all the covariates (adjusted OR 3.49, 95 CI% 2.24-5.44, p < 0.001). Our data show that the prevalence of GERD typical symptoms is higher in patients with NAFLD. GERD was associated with higher BMI and MetS, but not with age and diabetes type 2. NAFLD remained strongly associated with GERD, independently of a coexisting MetS status. Consistent with these findings, MetS can be considered a shared background, but cannot completely explain this correlation. We suggest NAFLD as an independent risk factor for GERD symptoms.

  17. Increased prevalence of intestinal inflammation in patients with liver cirrhosis

    PubMed Central

    Saitoh, Osamu; Sugi, Kazunori; Kojima, Keishi; Matsumoto, Hisashi; Nakagawa, Ken; Kayazawa, Masanobu; Tanaka, Seigou; Teranishi, Tsutomu; Hirata, Ichiro; Katsu, Ken-ichi

    1999-01-01

    AIM: To investigate the pathophysiology of the digestive tract in patients with liver cirrhosis. METHODS: In 42 cirrhotic patients and 20 control subjects, the following fecal proteins were measured by enzyme-linked immunosorbent assay: albumin (Alb), transferrin (Tf), and α1-antitrypsin (α1-AT) as a marker for intestinal protein loss, hemoglobin (Hb) for bleeding, PMN-elastase for intestinal inflammation, and secretory IgA for intestinal immunity. RESULTS: The fecal concentrations of Hb, Alb, Tf, α1-AT, an d PMN-elastase were increased in 13 (31%), 8 (19%), 10 (24%), 6 (14%), and 11 (26%) cases among 42 patients, respectively. Fecal concentration of secretory IgA was decreased in 7 (17%) of 42 patients. However, these fecal concentrations were not related to the severity or etiology of liver cirrhosis. The serum Alb level was significantly decreased in patients with intestinal protein loss compared to that in patients without intestinal protein loss. CONCLUSION: These findings suggest that: ① besides the well-known pathological conditions, such as bleeding and protein loss, intestinal inflammation and decreased intestinal immunity are found in cirrhotic patients; ② intestinal protein loss contributes to hypoalbuminemia in cirrhotic patients, and ③ intestinal inflammation should not be over looked in cirrhotic patients, since it may contribute to or cause intestinal protein loss and other various path ological conditions. PMID:11819475

  18. Risk Factors Associated with Increased Morbidity in Living Liver Donation

    PubMed Central

    Candido, Helry L.; da Fonseca, Eduardo A.; Feier, Flávia H.; Pugliese, Renata; Benavides, Marcel A.; Silva, Enis D.; Gordon, Karina; de Abreu, Marcelo Gama; Canet, Jaume; Chapchap, Paulo; Neto, Joao Seda

    2015-01-01

    Living donor liver donation (LDLD) is an alternative to cadaveric liver donation. We aimed at identifying risk factors and developing a score for prediction of postoperative complications (POCs) after LDLD in donors. This is a retrospective cohort study in 688 donors between June 1995 and February 2014 at Hospital Sírio-Libanês and A.C. Camargo Cancer Center, in São Paulo, Brazil. Primary outcome was POC graded ≥III according to the Clavien-Dindo classification. Left lateral segment (LLS), left lobe (LL), and right lobe resections (RL) were conducted in 492 (71.4%), 109 (15.8%), and 87 (12.6%) donors, respectively. In total, 43 (6.2%) developed POCs, which were more common after RL than LLS and LL (14/87 (16.1%) versus 23/492 (4.5%) and 6/109 (5.5%), resp., p < 0.001). Multivariate analysis showed that RL resection (OR: 2.81, 95% CI: 1.32 to 3.01; p = 0.008), smoking status (OR: 3.2, 95% CI: 1.35 to 7.56; p = 0.012), and blood transfusion (OR: 3.15, 95% CI: 1.45 to 6.84; p = 0.004) were independently associated with POCs. RL resection, intraoperative blood transfusion, and smoking were associated with increased risk for POCs in donors. PMID:26788361

  19. Risk Factors Associated with Increased Morbidity in Living Liver Donation.

    PubMed

    Candido, Helry L; da Fonseca, Eduardo A; Feier, Flávia H; Pugliese, Renata; Benavides, Marcel A; Silva, Enis D; Gordon, Karina; de Abreu, Marcelo Gama; Canet, Jaume; Chapchap, Paulo; Neto, Joao Seda

    2015-01-01

    Living donor liver donation (LDLD) is an alternative to cadaveric liver donation. We aimed at identifying risk factors and developing a score for prediction of postoperative complications (POCs) after LDLD in donors. This is a retrospective cohort study in 688 donors between June 1995 and February 2014 at Hospital Sírio-Libanês and A.C. Camargo Cancer Center, in São Paulo, Brazil. Primary outcome was POC graded ≥III according to the Clavien-Dindo classification. Left lateral segment (LLS), left lobe (LL), and right lobe resections (RL) were conducted in 492 (71.4%), 109 (15.8%), and 87 (12.6%) donors, respectively. In total, 43 (6.2%) developed POCs, which were more common after RL than LLS and LL (14/87 (16.1%) versus 23/492 (4.5%) and 6/109 (5.5%), resp., p < 0.001). Multivariate analysis showed that RL resection (OR: 2.81, 95% CI: 1.32 to 3.01; p = 0.008), smoking status (OR: 3.2, 95% CI: 1.35 to 7.56; p = 0.012), and blood transfusion (OR: 3.15, 95% CI: 1.45 to 6.84; p = 0.004) were independently associated with POCs. RL resection, intraoperative blood transfusion, and smoking were associated with increased risk for POCs in donors.

  20. Expanding Exposure: Can Increasing the Daily Duration of Head Start Reduce Childhood Obesity?

    ERIC Educational Resources Information Center

    Frisvold, David E.; Lumeng, Julie C.

    2011-01-01

    Coinciding with the work requirements of welfare reform in the mid-1990s, the early childhood education program, Head Start, significantly expanded to increase the availability of full-day classes. Using unique administrative data, we examine the effect of full-day compared to half-day attendance on childhood obesity. This effect is identified…

  1. An Affordance Network for Engagement: Increasing Parent and Family Agency in an Early Childhood Education Setting

    ERIC Educational Resources Information Center

    Clarkin-Phillips, Jeanette; Carr, Margaret

    2012-01-01

    Research from the United Kingdom suggests that early childhood centres that operate from a multi or integrated service model, offering opportunities for parents to attend to a range of their needs and aspirations, increase the ability and the inclination of families to engage with their child's learning at the early childhood centre. Integrated…

  2. Expanding Exposure: Can Increasing the Daily Duration of Head Start Reduce Childhood Obesity?

    ERIC Educational Resources Information Center

    Frisvold, David E.; Lumeng, Julie C.

    2011-01-01

    Coinciding with the work requirements of welfare reform in the mid-1990s, the early childhood education program, Head Start, significantly expanded to increase the availability of full-day classes. Using unique administrative data, we examine the effect of full-day compared to half-day attendance on childhood obesity. This effect is identified…

  3. The increasing burden of potentially preventable liver disease among adult liver transplant recipients: A comparative analysis of liver transplant indication by era in Australia and New Zealand.

    PubMed

    Howell, Jessica; Balderson, Glenda; Hellard, Margaret; Gow, Paul; Strasser, Simone; Stuart, Katherine; Wigg, Alan; Jeffrey, Gary; Gane, Ed; Angus, Peter W

    2016-02-01

    Hepatitis C (HCV), hepatitis B (HBV), alcohol-related liver disease (ALD), and non-alcohol-related fatty liver disease (NAFLD) are leading indications for adult liver transplantation in Australia and New Zealand. However, these diseases are potentially preventable through effective primary and/or secondary prevention strategies. This study evaluates the relative contribution of potentially preventable liver diseases to liver transplant numbers in Australia and New Zealand over time. Prospectively recorded clinical, demographic, and outcome data were collected from the Australian and New Zealand Liver Transplant Registry for all primary adult liver transplants performed in Australia and New Zealand from 1 January 1985 until 31 December 2012. Potentially preventable liver disease was defined as HBV, HCV, NAFLD, ALD, and HCC. The etiology of liver disease leading to liver transplantation and the proportion of preventable liver disease-related liver transplantation was compared between Era 1 (1985-1993), Era 2 (1994-2003), and Era 3 (2004-2012). Overall, 1252 of 3266 adult primary liver transplants (38.3%) were performed for potentially preventable liver disease. There was a significant increase in the proportion of liver transplants because of preventable liver disease from 21.2% (93 of 439) in Era 1, to 49.8% (623 of 1252) in Era 2 and 63.5% (1000 of 1575) in Era 3 (P < 0.0001). Over time, there was a significant increase in HCV (P < 0.0001), ALD (P = 0.002), and NAFLD (P < 0.0001) as a primary indication for adult liver transplant, whereas HBV has significantly decreased from Era 1 to Era 3 as an indication for transplant (P < 0.0001). The number of transplants performed for HCC also increased across Eras (P < 0.0001), with 84% due to underlying potentially preventable liver disease. Since 2004, the majority of primary adult liver transplants within Australia and New Zealand have been because of potentially preventable liver diseases and the

  4. Does breastfeeding increase risk of early childhood caries?

    PubMed

    Paglia, L

    2015-09-01

    According to the WHO, "breastfeeding is the normal way of providing young infants with the nutrients they need for healthy growth and development. Exclusive breastfeeding is recommended up to 6 months of age, with continued breastfeeding along with appropriate complementary foods up to two years of age or beyond". However, several studies have reported prolonged and unrestricted breastfeeding as a potential risk factor for primary tooth caries (ECC). On-demand breastfeeding, particularly while lying down at night, would seem to cause ECC because milk remains in the baby's mouth for long periods of time. There is lack of evidence that human milk is cariogenic; other factors, such as oral hygiene, may be more influential in caries development than on-demand breastfeeding. Moreover the biomechanics of breastfeeding differs from those of bottle feeding and milk is expressed into the soft palate and swallowed without remaining on teeth. Indeed we cannot forget that the main factor influencing caries development in infants is the presence of bacteria streptococcus mutans that thrives in a combination of sugars, small amounts of saliva and a low pH. Today the question is open and recently Chaffee, Felines, Vitolo et al. [2014] have found that breastfeeding for 24 months or longer increases the prevalence of severe early childhood caries in low-income families in Porto Alegre, Brazil. These results do not claim that prolonged breastfeeding is the cause of tooth decay; we can expect an association with food for infants often rich in refined sugars, which cause the reduction of the protective effect of saliva on the deciduous teeth enamel. In Japan, Kato, Yorifuji, Yamakawa et al. [2015] have found that infants who had been breastfed for at least 6 or 7 months, both exclusively and partially, were at elevated risk of dental caries at the age of 30 months compared with those who had been exclusively fed with formula. The authors themselves say, however, that further studies

  5. Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population-based cohort study.

    PubMed

    Asdahl, Peter Haubjerg; Winther, Jeanette Falck; Bonnesen, Trine Gade; De Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Holmqvist, Anna Sällfors; Malila, Nea; Tryggvadottir, Laufey; Wesenberg, Finn; Dahlerup, Jens Frederik; Olsen, Jørgen Helge; Hasle, Henrik

    2016-10-01

    Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects. © 2016 UICC.

  6. Childhood and later life stressors and increased inflammatory gene expression at older ages.

    PubMed

    Levine, M E; Cole, S W; Weir, D R; Crimmins, E M

    2015-04-01

    Adverse experiences in early life have the ability to "get under the skin" and affect future health. This study examined the relative influence of adversities during childhood and adulthood in accounting for individual differences in pro-inflammatory gene expression in late life. Using a pilot-sample from the Health and Retirement Study (N = 114) aged from 51 to 95, OLS regression models were run to determine the association between a composite score from three proinflammatory gene expression levels (PTGS2, ILIB, and IL8) and 1) childhood trauma, 2) childhood SES, 3) childhood health, 4) adult traumas, and 5) low SES in adulthood. Our results showed that only childhood trauma was found to be associated with increased inflammatory transcription in late life. Furthermore, examination of interaction effects showed that childhood trauma exacerbated the influence of low SES in adulthood on elevated levels of inflammatory gene expression-signifying that having low SES in adulthood was most damaging for persons who had experienced traumatic events during their childhood. Overall our study suggests that traumas experienced during childhood may alter the stress response, leading to more sensitive reactivity throughout the lifespan. As a result, individuals who experienced greater adversity in early life may be at higher risk of late life health outcomes, particularly if adulthood adversity related to SES persists. Copyright © 2015. Published by Elsevier Ltd.

  7. Hepatic splenosis mimicking liver metastases in a patient with history of childhood immature teratoma

    PubMed Central

    Trotovsek, Blaz; Skrbinc, Breda

    2016-01-01

    Abstract Background Hepatic splenosis is rare condition, preceded by splenectomy or spleen trauma, the term refers to nodular implantation of normal splenic tissue in the liver. In patients with history of malignancy in particular, it can be mistaken for metastases and can lead to unnecessary diagnostic procedures or inappropriate treatment. Case report Twenty-two-year old male was treated for immature teratoma linked to undescended right testicle after birth. On regular follow-up examinations no signs of disease relapse or long-term consequences were observed. He was presented with incidental finding of mature cystic teratoma after elective surgery for what appeared to be left-sided inguinal hernia. The tumour was most likely a metastasis of childhood teratoma. Origin within remaining left testicle was not found. Upon further imaging diagnostics, several intrahepatic lesions were revealed. Based on radiologic appearance they were suspicious to be metastases. The patient underwent two ultrasound guided fine-needle aspiration biopsies. Cytologic diagnosis was inconclusive. Histology of laparoscopically obtained tissue disclosed presence of normal splenic tissue and led to diagnosis of hepatic splenosis. Conclusions Though hepatic splenosis is rare, it needs to be included in differential diagnosis of nodular hepatic lesions. Accurate interpretation of those lesions is crucial for appropriate management of the patient. If diagnosis eludes after cytologic diagnostics alone, laparoscopic excision of nodular lesion is warranted before considering more extensive liver resection. PMID:27247554

  8. Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury

    PubMed Central

    Cho, Young-Eun; Im, Eun-Ju; Moon, Pyong-Gon; Mezey, Esteban; Song, Byoung-Joon; Baek, Moon-Chang

    2017-01-01

    Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury. The circulating EVs, isolated from plasma of APAP-exposed, ethanol-fed mice, or alcoholic hepatitis patients versus normal control counterparts, were characterized by proteomics and biochemical methods. Liver specific EV proteins were analyzed by immunoblots and ELISA. The amounts of total and liver-specific proteins in circulating EVs from APAP-treated mice significantly increased in a dose- and time-dependent manner. Proteomic analysis of EVs from APAP-exposed mice revealed that the amounts of liver-specific and/or hepatotoxic proteins were increased compared to those of controls. Additionally, the increased protein amounts in EVs following APAP exposure returned to basal levels when mice were treated with N-acetylcysteine or glutathione. Similar results of increased amounts and liver-specific proteins in circulating EVs were also observed in mice exposed to hepatotoxic doses of thioacetamide or d-galactosamine but not by non-hepatotoxic penicillin or myotoxic bupivacaine. Additionally, binge ethanol exposure significantly elevated liver-specific proteins in circulating EVs from mice and alcoholics with alcoholic hepatitis, compared to control counterparts. These results indicate that circulating EVs in drug- and alcohol-mediated hepatic injury contain liver-specific proteins that could serve as specific biomarkers for hepatotoxicity. PMID:28225807

  9. Childhood obesity: a review of increased risk for physical and psychological comorbidities.

    PubMed

    Pulgarón, Elizabeth R

    2013-01-01

    Worldwide estimates of childhood overweight and obesity are as high as 43 million, and rates continue to increase each year. Researchers have taken interest in the childhood obesity epidemic and the impact of this condition across health domains. The consequences of childhood and adolescent obesity are extensive, including both medical and psychosocial comorbidities. The purpose of this review was to consolidate and highlight the recent literature on the comorbidities associated with childhood obesity, both nationally and internationally. PubMed and PsychINFO searches were conducted on childhood obesity and comorbidities. The initial search of the terms obesity and comorbidity yielded >5000 published articles. Limits were set to include studies on children and adolescents that were published in peer-reviewed journals from 2002 to 2012. These limits narrowed the search to 938. Review of those articles resulted in 79 that are included in this review. The major medical comorbidities associated with childhood obesity in the current literature are metabolic risk factors, asthma, and dental health issues. Major psychological comorbidities include internalizing and externalizing disorders, attention-deficit hyperactivity disorder, and sleep problems. The high prevalence rates of childhood obesity have resulted in extensive research in this area. Limitations to the current childhood obesity literature include differential definitions of weight status and cut-off levels for metabolic risk factors across studies. Additionally, some results are based on self-report of diagnoses rather than chart reviews or physician diagnosis. Even so, there is substantial support for metabolic risk factors, internalizing disorders, attention-deficit hyperactivity disorder, and decreased health-related quality of life as comorbidities to obesity in childhood. Additional investigations on other diseases and conditions that might be associated with childhood obesity are warranted and

  10. Malnutrition induces gut atrophy and increases hepatic fat infiltration: studies in a pig model of childhood malnutrition

    PubMed Central

    Lykke, Mikkel; Hother, Anne-Louise; Hansen, Christian F; Friis, Henrik; Mølgaard, Christian; Michaelsen, Kim F; Briend, André; Larsen, Torben; Sangild, Per T; Thymann, Thomas

    2013-01-01

    Childhood malnutrition is a problem in developing countries, and pathological changes in digestive organs such as the intestine and liver are poorly understood. An animal model to study the progression of severe acute malnutrition could elucidate pathological changes in the intestine and liver. We sought to characterize growth and clinical changes during malnutrition related to structural and functional indices in the intestine and liver. Newly weaned piglets were given ad libitum access to a maize flour diet (MAIZE, n=9) or a nutritionally optimized reference diet (REFERENCE, n=12) for 7 weeks. Growth, hematology and clinical biochemistry where recorded weekly. After 7 weeks, the MAIZE pigs had lower body weights than the REF pigs (8.3 kg vs. 32.4 kg, P < 0.001), indicating severe stunting and moderate to severe wasting. This was paralleled by lower values for hematocrit, hemoglobin and mean cell volume in MAIZE vs. REFERENCE (P < 0.01), indicating anemia. Although the observed temporal changes in MAIZE were associated with atrophy of the small intestinal mucosa (P < 0.001), digestive enzyme activity was only marginally reduced. Serum alanine aminotransferase, bilirubin and albumin were increased in the MAIZE pigs (P < 0.001), and the liver had a vacuolated appearance and tendency toward increased triglyceride content (P=0.054). We conclude that liver and intestinal indices are compromised during malnutrition and are associated with temporal changes in growth and hematological and biochemical endpoints. The pig model is relevant for malnourished infants and can act as a valuable tool for understanding the pathophysiology of malnutrition. PMID:23977413

  11. An Increasing Socioeconomic Gap in Childhood Overweight and Obesity in China

    PubMed Central

    James, Sherman A.; Merli, M. Giovanna; Zheng, Hui

    2014-01-01

    We used a new conceptual framework that integrates tenets from health economics, social epidemiology, and health behavior to analyze the impact of socioeconomic forces on the temporal changes in the socioeconomic status (SES) gap in childhood overweight and obesity in China. In data from the China Health and Nutrition Survey for 1991 to 2006, we found increased prevalence of childhood overweight and obesity across all SES groups, but a greater increase among higher-SES children, especially after 1997, when income inequality dramatically increased. Our findings suggest that for China, the increasing SES gap in purchasing power for obesogenic goods, associated with rising income inequality, played a prominent role in the country’s increasing SES gap in childhood obesity and overweight. PMID:24228657

  12. An increasing socioeconomic gap in childhood overweight and obesity in China.

    PubMed

    He, Wei; James, Sherman A; Merli, M Giovanna; Zheng, Hui

    2014-01-01

    We used a new conceptual framework that integrates tenets from health economics, social epidemiology, and health behavior to analyze the impact of socioeconomic forces on the temporal changes in the socioeconomic status (SES) gap in childhood overweight and obesity in China. In data from the China Health and Nutrition Survey for 1991 to 2006, we found increased prevalence of childhood overweight and obesity across all SES groups, but a greater increase among higher-SES children, especially after 1997, when income inequality dramatically increased. Our findings suggest that for China, the increasing SES gap in purchasing power for obesogenic goods, associated with rising income inequality, played a prominent role in the country's increasing SES gap in childhood obesity and overweight.

  13. [Liver and spleen biometrics in childhood-onset systemic lupus erythematosus patients].

    PubMed

    Guariento, Andressa; Silva, Marco Felipe C; Tassetano, Priscilla S F; Rocha, Sílvia Maria S; Campos, Lúcia M A; Valente, Marcelo; Silva, Clovis A

    2015-01-01

    To evaluate liver and spleen dimensions in childhood-onset systemic lupus erythematosus (c-SLE) patients and healthy controls. 30 c-SLE patients and 30 healthy control volunteers underwent abdominal ultrasound. The following two liver measurements were performed in left hepatic lobe: craniocaudal and anteroposterior and three in right hepatic lobe (RHL): posterior craniocaudal (PCC-RHL), anterior craniocaudal and anteroposterior. Three spleen dimension measurements were also evaluated: longitudinal, transverse and anteroposterior. Demographic, clinical and laboratorial data, SLEDAI-2K, ECLAM, SLAM and treatment were assessed. Mean current age was similar in c-SLE and controls (170.31 ± 27.81 vs. 164.15 ± 39.25 months; p = 0.486). The mean of PCC-RHL dimension was significantly higher in c-SLE compared to controls (13.30 ± 1.85 vs. 12.52 ± 0.93, p = 0.044). There were no differences between the other hepatic biometrics and splenic parameters (p > 0.05). Further analysis in c-SLE patients according to PCC-RHL dimension ≥ 13.3cm versus < 13.3 cm showed that the median of SLEDAI-2K [8(0-18) vs. 2(0-8), p=0.004], ECLAM [4(0-9) vs. 2(0-5), p = 0.019] and SLAM [5(1-13) vs. 2(0-14), p = 0.016] were significantly higher in patients with higher PCC-RHL dimension, likewise the frequencie of nephritis (77% vs. 29%, p = 0.010). Liver enzymes were similar in both groups (p > 0.05). Positive correlation was observed between SLEDAI-2K and PCC-RHL (p = 0.001, r = +0.595). Negative correlation was evidenced between disease duration and longitudinal dimension of spleen (p = 0.031, r = -0.394). Our data raises the possibility that disease activity could lead to a subclinical and localized hepatomegaly during the disease course. Long disease duration resulted to spleen atrophy in c-SLE patients. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

  14. Childhood adversity increases vulnerability for behavioral symptoms and immune dysregulation in women with breast cancer.

    PubMed

    Witek Janusek, Linda; Tell, Dina; Albuquerque, Kevin; Mathews, Herbert L

    2013-03-01

    Women respond differentially to the stress-associated with breast cancer diagnosis and treatment, with some women experiencing more intense and/or sustained behavioral symptoms and immune dysregulation than others. Childhood adversity has been identified to produce long-term dysregulation of stress response systems, increasing reactivity to stressors encountered during adulthood. This study determined whether childhood adversity increased vulnerability for more intense and sustained behavioral symptoms (fatigue, perceived stress, and depressive symptoms), poorer quality of life, and greater immune dysregulation in women (N=40) with breast cancer. Evaluation was after breast surgery and through early survivorship. Hierarchical linear modeling was used to examine intra-individual and inter-individual differences with respect to initial status and to the pattern of change (i.e. trajectory) of outcomes. At initial assessment, women exposed to childhood emotional neglect/abuse had greater perceived stress, fatigue, depressive symptoms and poorer quality of life, as well as lower natural killer cell activity (NKCA). Although these outcomes improved over time, women with greater childhood emotional neglect/abuse exhibited worse outcomes through early survivorship. No effect was observed on the pattern of change for these outcomes. In contrast, childhood physical neglect predicted sustained trajectories of greater perceived stress, worse quality of life, and elevated plasma IL-6; with no effect observed at initial assessment. Thus, childhood adversity leaves an enduring imprint, increasing vulnerability for behavioral symptoms, poor quality of life, and elevations in IL-6 in women with breast cancer. Further, childhood adversity predisposes to lower NKCA at a critical time when this immune-effector mechanism is most effective at halting nascent tumor seeding.

  15. Childhood cod liver oil consumption and bone mineral density in a population-based cohort of peri- and postmenopausal women: the Nord-Trondelag Health Study.

    PubMed

    Forsmo, Siri; Fjeldbo, Sigurd Kjørstad; Langhammer, Arnulf

    2008-02-15

    Use of cod liver oil, which is rich in vitamins A and D, is traditionally recommended during the fall and winter months as a protective measure against vitamin D deficiency in several countries. It is not known whether childhood cod liver oil intake is related to variations in bone mineral density (BMD) or fractures in adult life. In 2001, a total of 3,052 Norway women aged 50-70 years had forearm BMD measured in a substudy of the population-based Nord-Trøndelag Health Study. Women reporting no childhood cod liver oil intake had statistically significantly higher BMD than those with any ingestion of cod liver oil. The odds ratio for low BMD (>1 standard deviation below age-specific mean) in women reporting cod liver oil intake throughout the year as compared with women with no intake was 2.3 (95% confidence interval: 1.4, 3.9), adjusted for body mass index, smoking, menopausal status, estrogen use, and current milk consumption. There were indications of a negative dose-response effect of childhood cod liver oil intake on bone. Although the vitamin A content of commercial cod liver oil was recently reduced by 75% in Norway, the past high concentration remains a possible explanation for the observed negative association between childhood cod liver oil intake and forearm BMD.

  16. Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals

    PubMed Central

    van Rooij, Sanne J. H.; Stevens, Jennifer S.; Ely, Timothy D.; Fani, Negar; Smith, Alicia K.; Kerley, Kimberly A.; Lori, Adriana; Ressler, Kerry J.; Jovanovic, Tanja

    2016-01-01

    Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes. PMID:27683563

  17. Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals.

    PubMed

    van Rooij, Sanne J H; Stevens, Jennifer S; Ely, Timothy D; Fani, Negar; Smith, Alicia K; Kerley, Kimberly A; Lori, Adriana; Ressler, Kerry J; Jovanovic, Tanja

    2016-01-01

    Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes.

  18. Does Childhood Disability Increase Risk for Child Abuse and Neglect?

    ERIC Educational Resources Information Center

    Leeb, Rebecca T.; Bitsko, Rebecca H.; Merrick, Melissa T.; Armour, Brian S.

    2012-01-01

    In this article we review the empirical evidence for the presumptions that children with disabilities are at increased risk for child maltreatment, and parents with disabilities are more likely to perpetrate child abuse and neglect. Challenges to the epidemiological examination of the prevalence of child maltreatment and disabilities are…

  19. Does Childhood Disability Increase Risk for Child Abuse and Neglect?

    ERIC Educational Resources Information Center

    Leeb, Rebecca T.; Bitsko, Rebecca H.; Merrick, Melissa T.; Armour, Brian S.

    2012-01-01

    In this article we review the empirical evidence for the presumptions that children with disabilities are at increased risk for child maltreatment, and parents with disabilities are more likely to perpetrate child abuse and neglect. Challenges to the epidemiological examination of the prevalence of child maltreatment and disabilities are…

  20. Investing in Early Childhood: Increasing Funding for Smart Start Programs

    ERIC Educational Resources Information Center

    Voices for America's Children, 2005

    2005-01-01

    In 2004, Voices for America's Children member Kansas Action for Children, partnered with state and local organizations to increase funding for Smart Start Kansas, a successful early care and education program. Kansas Children's Campaign, an initiative of Kansas Action for Children, collaborated with a key state organization, legislators,…

  1. Exposure to the Chinese Famine in Childhood Increases Type 2 Diabetes Risk in Adults.

    PubMed

    Wang, Jing; Li, Yaru; Han, Xu; Liu, Bing; Hu, Hua; Wang, Fei; Li, Xiulou; Yang, Kun; Yuan, Jing; Yao, Ping; Miao, Xiaoping; Wei, Sheng; Wang, Youjie; Liang, Yuan; Zhang, Xiaomin; Guo, Huan; Yang, Handong; Hu, Frank B; Wu, Tangchun; He, Meian

    2016-11-01

    Evidence shows that exposure to poor conditions in early life is associated with an increased risk of chronic diseases in adults. We investigated whether exposure to the Chinese famine (1959-1961) in the fetal stage or in childhood (0-9 y) was associated with type 2 diabetes (T2D) and hyperglycemia in adulthood. We included 7801 subjects aged 56.4 ± 3.3 y from the Dongfeng-Tongji cohort. Subjects were classified into late-, middle-, and early-childhood-exposed, fetal-exposed, and unexposed groups. Excess mortality rate was used to evaluate the severity of famine. Logistic regression models were used to analyze the famine-dysglycemia associations. Generalized linear models were used to assess the famine effects on dysglycemia risk during the 5-y follow-up period among 3100 subjects. In descriptive analyses, the risk of T2D was significantly greater in the middle-childhood-exposed group (OR: 1.44; 95% CI: 1.10, 1.87; P = 0.007), and the risk of hyperglycemia was higher in the middle- and late-childhood-exposed groups than in the unexposed group (OR: 1.54; 95% CI: 1.26, 1.88 and OR: 1.51; 95% CI: 1.23, 1.85, respectively). In sex-specific analyses, women exposed in middle childhood (OR: 1.55; 95% CI: 1.16, 2.06) and late childhood (OR: 1.40; 95% CI: 1.05, 1.87) had a higher risk of T2D than unexposed women. This association was not found in men. Similar associations were found for hyperglycemia risk. Moreover, subjects who experienced severe famine in childhood had a 38% higher T2D risk (95% CI: 1.05, 1.81) than those exposed to less severe famine. In retrospective cohort analyses, participants who experienced famine in middle childhood had a higher hyperglycemia risk relative to the unexposed group (RR: 2.06; 95% CI: 1.08, 3.90). Exposure to the Chinese famine in childhood was related to an increased risk of adulthood T2D and hyperglycemia, particularly in women. © 2016 American Society for Nutrition.

  2. Study Finds Small Increase in Cancer Risk after Childhood CT Scans

    Cancer.gov

    A study published in the June 6, 2012, issue of The Lancet shows that radiation exposure from computed tomography (CT) scans in childhood results in very small but increased risks of leukemia and brain tumors in the first decade after exposure.

  3. Childhood-Onset Bipolar Disorder: Evidence for Increased Familial Loading of Psychiatric Illness

    ERIC Educational Resources Information Center

    Rende, Richard; Birmaher, Boris; Axelson, David; Strober, Michael; Gill, Mary Kay; Valeri, Sylvia; Chiappetta, Laurel; Ryan, Neal; Leonard, Henrietta; Hunt, Jeffrey; Iyengar, Satish; Keller, Martin

    2007-01-01

    Objective: To determine whether childhood-onset bipolar disorder (BP) is associated with an increased psychiatric family history compared with adolescent-onset BP. Method: Semistructured psychiatric interviews were conducted for 438 youth with BP spectrum disorders. To evaluate the effects of age at onset and psychiatric family history, the sample…

  4. Childhood-Onset Bipolar Disorder: Evidence for Increased Familial Loading of Psychiatric Illness

    ERIC Educational Resources Information Center

    Rende, Richard; Birmaher, Boris; Axelson, David; Strober, Michael; Gill, Mary Kay; Valeri, Sylvia; Chiappetta, Laurel; Ryan, Neal; Leonard, Henrietta; Hunt, Jeffrey; Iyengar, Satish; Keller, Martin

    2007-01-01

    Objective: To determine whether childhood-onset bipolar disorder (BP) is associated with an increased psychiatric family history compared with adolescent-onset BP. Method: Semistructured psychiatric interviews were conducted for 438 youth with BP spectrum disorders. To evaluate the effects of age at onset and psychiatric family history, the sample…

  5. Pediatric non-alcoholic fatty liver disease: an increasing public health issue.

    PubMed

    Berardis, S; Sokal, E

    2014-02-01

    Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition that encompasses a wide spectrum of liver abnormalities ranging from simple liver steatosis to steatohepatitis (non-alcoholic steatohepatitis), which may be associated with fibrosis and progress to cirrhosis and end-stage liver disease. NAFLD has recently become the most common cause of chronic liver disease in children and adolescents. NAFLD prevalence, alongside obesity, continues to increase among pediatric patients. Obesity is believed to represent a major risk factor for NAFLD, which is considered to be the liver presentation of the metabolic syndrome. Although the pathogenesis of NAFLD is not fully understood, the notion that multiple factors affect disease development and progression is widely accepted. Both genetic background and environmental factors contribute to NAFLD development. A more complete understanding of the pathogenesis may aid in developing non-invasive diagnostic tools and identifying new therapeutic targets. Liver biopsy currently remains the gold standard for NAFLD diagnosis and staging. Although lifestyle and diet modifications are key in NAFLD treatment, the development of new pharmacological therapies is crucial for patients who are unresponsive to first-line therapy. Pediatric NAFLD is an increasing public health issue that remains underdiagnosed. A large-scale screening in the high-risk population, especially among the overweight pediatric patients, should be considered, including measurement of serum transaminases and liver ultrasound. It is crucial to treat this condition as soon as possible in order to avoid the progression to end-stage liver disease.

  6. Prenatal acetaminophen induces liver toxicity in dams, reduces fetal liver stem cells, and increases airway inflammation in adult offspring.

    PubMed

    Karimi, Khalil; Keßler, Timo; Thiele, Kristin; Ramisch, Katherina; Erhardt, Annette; Huebener, Peter; Barikbin, Roja; Arck, Petra; Tiegs, Gisa

    2015-05-01

    During pregnancy, acetaminophen is one of the very few medications recommended by physicians to treat fever or pain. Recent insights from epidemiological studies suggest an association between prenatal acetaminophen medication and an increased risk for development of asthma in children later in life. The underlying pathogenesis of such association is still unknown. We aimed to develop a mouse model to provide insights into the effect of prenatal acetaminophen on maternal, fetal and adult offspring's health. The toxic effect of acetaminophen was studied in mice on 1) maternal liver; mirrored by biomarkers of liver injury, centrilobular necrosis, and infiltration of granulocytes; 2) fetal liver; reflected by the frequency of hematopoietic stem cells, and 3) postnatal health; evaluated by the severity of allergic airway inflammation among offspring. We observed an increased susceptibility towards acetaminophen-induced liver damage in pregnant mice compared to virgins. Moreover, hematopoietic stem cell frequency in fetal liver declined in response to acetaminophen. Furthermore, a greater severity of airway inflammation was observed in offspring of dams upon prenatal acetaminophen treatment, identified lung infiltration by leukocytes and eosinophil infiltration into the airways. Our newly developed mouse model on prenatal use of acetaminophen reflects findings from epidemiological studies in humans. The availability of this model will allow improvement in our understanding of how acetaminophen-related hepatotoxicity is operational in pregnant individuals and how an increased risk for allergic diseases in response to prenatal acetaminophen is mediated. Such insights, once available, may change the recommendations for prenatal acetaminophen use. Copyright © 2014 European Association for the Study of the Liver. All rights reserved.

  7. Liver congestion in heart failure contributes to inappropriately increased serum hepcidin despite anemia.

    PubMed

    Ohno, Yukako; Hanawa, Haruo; Jiao, Shuang; Hayashi, Yuka; Yoshida, Kaori; Suzuki, Tomoyasu; Kashimura, Takeshi; Obata, Hiroaki; Tanaka, Komei; Watanabe, Tohru; Minamino, Tohru

    2015-01-01

    Hepcidin is a key regulator of mammalian iron metabolism and mainly produced by the liver. Hepcidin excess causes iron deficiency and anemia by inhibiting iron absorption from the intestine and iron release from macrophage stores. Anemia is frequently complicated with heart failure. In heart failure patients, the most frequent histologic appearance of liver is congestion. However, it remains unclear whether liver congestion associated with heart failure influences hepcidin production, thereby contributing to anemia and functional iron deficiency. In this study, we investigated this relationship in clinical and basic studies. In clinical studies of consecutive heart failure patients (n = 320), anemia was a common comorbidity (41%). In heart failure patients without active infection and ongoing cancer (n = 30), log-serum hepcidin concentration of patients with liver congestion was higher than those without liver congestion (p = 0.0316). Moreover, in heart failure patients with liver congestion (n = 19), the anemia was associated with the higher serum hepcidin concentrations, which is a type of anemia characterized by induction of hepcidin. Subsequently, we produced a rat model of heart failure with liver congestion by injecting monocrotaline that causes pulmonary hypertension. The monocrotaline-treated rats displayed liver congestion with increase of hepcidin expression at 4 weeks after monocrotaline injection, followed by anemia and functional iron deficiency observed at 5 weeks. We conclude that liver congestion induces hepcidin production, which may result in anemia and functional iron deficiency in some patients with heart failure.

  8. Increased serum levels of lipogenic enzymes in patients with severe liver steatosis

    PubMed Central

    2012-01-01

    Background Lipid metabolism is altered in subjects with liver steatosis. FAS is a key enzyme in de novo lipogenesis and both FAS gene expression and enzymatic activity are primarily regulated by metabolic signals in the liver. Lipoprotein lipase (LPL), the rate-limiting enzyme for the hydrolysis of core triglycerides, plays a pivotal role in lipid metabolism. This study aims to investigate if circulating levels of FAS and LPL could be clinically associated with liver steatosis. Methods In this work, we present data obtained from a subsample of 94 subjects with liver steatosis enrolled by NUTRIEPA study, a nutritional trial in subjects with liver steatosis. Serum levels of FAS protein and LPL activity were evaluated by ELISA test and by a fluorescent method, respectively. The diagnosis and the degree of liver steatosis were based on laboratory and ecographic measurements. Statistical methods included Kruskal-Wallis analysis of variance and Wilcoxon signed-rank test, where appropriate. The χ2 test has been performed to analyse categorical variables. Results The subjects with severe steatosis had significantly higher serum levels of FAS protein and LPL activity compared to subjects with mild and moderate liver steatosis. Moreover, a positive trend in serum levels of FAS expression from lower to higher degree of steatosis was also detected. Conclusions We describe a relationship between human liver steatosis and elevated levels of circulating lipogenic enzymes. Increased serum levels of FAS expression and LPL activity could be considered a marker of severe liver steatosis. PMID:23110339

  9. Relationship between Neck Circumference and Non-Alcoholic Fatty Liver Disease in Childhood Obesity.

    PubMed

    Hatipoğlu, Nihal; Doğan, Serap; Mazıcıoğlu, M Mümtaz; Kurtoğlu, Selim

    2016-03-05

    The aim of this study was to establish the association between anthropometric parameters and non-alcoholic fatty liver disease (NAFLD) and to determine the most reliable measurement as a parameter in predicting NAFLD. Two-hundred fifty-three obese children of ages 10 to 18 years were enrolled in this study. Anthropometric data and metabolic parameters such as fasting blood glucose, insulin and lipid levels, were measured. Liver function tests were assessed. NAFLD was determined by ultrasound. Most metabolic parameters and anthropometric indices were significantly higher in children with NAFLD. A univariate logistic regression analysis was performed, taking NAFLD status as the dependent variable and anthropometric parameters as the independent variables. NAFLD was affected significantly by the anthropometric values. The multiple logistic regression analysis showed that neck circumference (NC) was the only parameter which determined the risk in both genders. Each 1 cm increase in the NC increased the risk of NAFLD 1.544-fold (p<0.001, 95% confidence interval (CI): 1.357-2.214) in the boys and 1.733-fold (p=0.001, 95% CI: 1.185-2.012) in the girls. Receiver operating characteristic analysis was performed to compare the reliability of anthropometric measurements. NC was observed to be a better indicator. Measurement of the NC was shown to be associated with NAFLD in children. We suggest the use of NC as a novel, simple, practical, and reliable anthropometric index in predicting children at risk for NAFLD.

  10. Relationship between Neck Circumference and Non-Alcoholic Fatty Liver Disease in Childhood Obesity

    PubMed Central

    Hatipoğlu, Nihal; Doğan, Serap; Mazıcıoğlu, M. Mümtaz; Kurtoğlu, Selim

    2016-01-01

    Objective: The aim of this study was to establish the association between anthropometric parameters and non-alcoholic fatty liver disease (NAFLD) and to determine the most reliable measurement as a parameter in predicting NAFLD. Methods: Two-hundred fifty-three obese children of ages 10 to 18 years were enrolled in this study. Anthropometric data and metabolic parameters such as fasting blood glucose, insulin and lipid levels, were measured. Liver function tests were assessed. NAFLD was determined by ultrasound. Results: Most metabolic parameters and anthropometric indices were significantly higher in children with NAFLD. A univariate logistic regression analysis was performed, taking NAFLD status as the dependent variable and anthropometric parameters as the independent variables. NAFLD was affected significantly by the anthropometric values. The multiple logistic regression analysis showed that neck circumference (NC) was the only parameter which determined the risk in both genders. Each 1 cm increase in the NC increased the risk of NAFLD 1.544-fold (p<0.001, 95% confidence interval (CI): 1.357-2.214) in the boys and 1.733-fold (p=0.001, 95% CI: 1.185-2.012) in the girls. Receiver operating characteristic analysis was performed to compare the reliability of anthropometric measurements. NC was observed to be a better indicator. Conclusion: Measurement of the NC was shown to be associated with NAFLD in children. We suggest the use of NC as a novel, simple, practical, and reliable anthropometric index in predicting children at risk for NAFLD. PMID:26758497

  11. Rapid neonatal weight gain increases risk of childhood overweight in offspring of diabetic mothers.

    PubMed

    Plagemann, Andreas; Harder, Thomas; Rodekamp, Elke; Kohlhoff, Rainer

    2012-09-01

    Increased neonatal weight gain has been suggested as risk factor for later overweight. Offspring of diabetic mothers (ODM) have a long-term increased overweight risk. However, the role of early postnatal weight gain for later overweight has not been addressed so far in ODM. We investigated whether increased weight gain during the first 4 months is related to later overweight in ODM. Determinants of childhood overweight and neonatal weight gain were analyzed in 152 ODM from the Kaulsdorf Cohort Study by MANOVA and regression analyses. Independent of birth weight, weight gain during the first 4 months was positively related to childhood relative body weight (P=0.001). Each 100 g-increase in weight during this period increased overweight risk by 65% (95%CI: 10-247%). ODM with rapid early weight gain had a more than six-fold increased risk of later overweight (OR: 6.77; 95%CI: 1.36-33.6). Early neonatal intake of breast milk from metabolically healthy mothers protected from rapid early weight gain (P=0.03). Increased weight gain during the first 4 months of life is a strong, independent risk factor for childhood overweight in ODM. Preventing nutritionally-induced rapid early weight gain in ODM might be a promising strategy to lower their long-term overweight risk.

  12. Coffee consumption protects against progression in liver cirrhosis and increases long-term survival after liver transplantation.

    PubMed

    Friedrich, Kilian; Smit, Mark; Wannhoff, Andreas; Rupp, Christian; Scholl, Sabine G; Antoni, Christoph; Dollinger, Matthias; Neumann-Haefelin, Christoph; Stremmel, Wolfgang; Weiss, Karl Heinz; Schemmer, Peter; Gotthardt, Daniel Nils

    2016-08-01

    Therapeutic options to treat progression of end-stage liver disease (ESLD) or improve long-term survival after liver transplantation remain scarce. We investigated the impact of coffee consumption under these conditions. We recorded coffee consumption habits of 379 patients with ESLD awaiting liver transplantation and 260 patients after liver transplantation. Survival was analyzed based on coffee intake. One hundred ninety-five patients with ESLD consumed coffee on a daily basis, while 184 patients did not. Actuarial survival was impaired (P = 0.041) in non-coffee drinkers (40.4 ± 4.3 months, 95% confidence interval [CI]: 32.0-48.9) compared with coffee drinkers (54.9 ± 5.5 months, 95% CI: 44.0-65.7). In subgroup analysis, the survival of patients with alcoholic liver disease (ALD; P = 0.020) and primary sclerosing cholangitis (PSC; P = 0.017) was increased with coffee intake while unaffected in patients with chronic viral hepatitis (P = 0.517) or other liver disease entities (P = 0.652). Multivariate analysis showed that coffee consumption of PSC and ALD patients retained as an independent risk factor (odds ratio [OR]: 1.94; 95% CI: 1.15-3.28; P = 0.013) along with MELD score (OR: 1.13; 95% CI: 1.09-1.17; P = 0.000). Following liver transplantation, long-term survival was longer in coffee drinkers (coffee: 61.8 ± 2.0 months, 95% CI: 57.9-65.8) than non-drinkers (52.3 ± 3.5 months, 95% CI: 45.4-59.3; P = 0.001). Coffee consumption delayed disease progression in ALD and PSC patients with ESLD and increased long-term survival after liver transplantation. We conclude that regular coffee intake might be recommended for these patients. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  13. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease.

    PubMed

    Estes, Chris; Razavi, Homie; Loomba, Rohit; Younossi, Zobair; Sanyal, Arun J

    2017-08-12

    Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are highly prevalent in the US, where they are a growing cause of cirrhosis and hepatocellular carcinoma (HCC), and increasingly, an indicator for liver transplantation. A Markov model was used to forecast NAFLD disease progression. Incidence of NAFLD was based on historical and projected changes in adult prevalence of obesity and type 2 diabetes mellitus (DM). Assumptions were derived from published literature where available, and validated using national surveillance data for incidence of NAFLD-related HCC. Projected changes in NAFLD-related cirrhosis, advanced liver disease, and liver-related mortality were quantified through 2030. Prevalent NAFLD cases are forecasted to increase 21%, from 83.1 (2015) to 100.9 million (2030), while prevalent NASH cases will increase 63% from 16.52 to 27.00 million cases. Overall NAFLD prevalence among the adult population (aged ≥15 years) is projected at 33.5% in 2030, and the median age of the NAFLD population will increase from 50 to 55 years during 2015-2030. In 2015, approximately 20% of NAFLD cases were classified as NASH, increasing to 27% by 2030, a reflection of both disease progression and an aging population. Incidence of decompensated cirrhosis will increase 168% to 105,430 cases by 2030, while incidence of HCC will increase by 137% to 12,240 cases. Liver deaths will increase 178% to an estimated 78,300 deaths in 2030. During 2015-2030, there are nearly 800,000 excess liver deaths. With continued high rates of adult obesity and DM, and an aging population, NAFLD-related liver disease and mortality will increase in the US. Strategies to slow the growth of NAFLD cases and therapeutic options are necessary to mitigate disease burden. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  14. Chronic non-cholestatic liver disease is not associated with an increased fracture rate in children.

    PubMed

    Konstantynowicz, Jerzy; Lebensztejn, Dariusz M; Skiba, Elzbieta; Sobaniec-Lotowska, Maria E; Abramowicz, Pawel; Piotrowska-Jastrzebska, Janina; Kaczmarski, Maciej

    2011-05-01

    Chronic liver disease in adults is a risk factor of osteoporosis, but little is known about risk of fractures in children with non-cholestatic liver disease. The aim of this study was to investigate associations among the severity of liver fibrosis, bone mass and low-energy fractures in children. History of fractures, anthropometry, and bone mass and size were examined in 39 Caucasian children (25 boys, 14 girls) aged 7.1-18 years (mean 11.9 ± 3.1) with chronic hepatitis B and liver fibrosis evidenced by liver biopsy. Severity of liver fibrosis was based on histological classification according to the method of Batts and Ludwig (mild, 1-2 scores; advanced, 3 scores) and Ishak (1-3 and 4-5 scores, respectively). Bone mineral content (BMC), density (BMD) and body composition were determined in the total body and lumbar spine using dual energy X-ray absorptiometry. Seven subjects (4 girls, 3 boys; 18% of the sample) had low BMD in the total body and lumbar spine region (Z-scores below -2.0). No associations were found among BMC, BMD, bone size and the severity of liver fibrosis. Nine boys (36% of all boys) and one girl reported repeated fractures (forearm, wrist, tibia, ankle, humerus), showing trends similar to the prevalence in general population. Fractures were neither associated with lower BMD/BMC nor with scores of liver fibrosis. Deficits in BMD in children with chronic hepatitis B are not associated with the severity of liver fibrosis. This study suggests that non-cholestatic liver disease does not increase the risk of low-energy fractures during growth. From the practical perspective, however, children with chronic liver disease should be screened for history and clinical risk factors for fractures rather than referred to bone density testing.

  15. Weight trajectories through infancy and childhood and risk of non-alcoholic fatty liver disease in adolescence: the ALSPAC study.

    PubMed

    Anderson, Emma L; Howe, Laura D; Fraser, Abigail; Callaway, Mark P; Sattar, Naveed; Day, Chris; Tilling, Kate; Lawlor, Debbie A

    2014-09-01

    Adiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of infant and childhood adiposity with subsequent NAFLD risk. We examined associations of weight-for-height trajectories from birth to age 10 with liver outcomes in adolescence, and assessed the extent to which associations are mediated through fat mass at the time of outcome assessment. Individual trajectories of weight and height were estimated for participants in the Avon Longitudinal Study of Parents and Children using random-effects linear-spline models. Associations of birthweight (adjusted for birth length) and weight change (adjusted for length/height change) from 0-3 months, 3 months-1 y, 1-3 y, 3-7 y, and 7-10 y with ultrasound scan (USS) determined liver fat and stiffness, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) at mean age 17.8 y were assessed with linear and logistic regressions. Mediation by concurrent fat mass was assessed with adjustment for fat mass at mean age 17.8 y. Birth weight was positively associated with liver stiffness and negatively with ALT and AST. Weight change from birth to 1 y was not associated with outcomes. Weight change from 1-3 y, 3-7 y, and 7-10 y was consistently positively associated with USS and blood-based liver outcomes. Adjusting for fat mass at mean age 17.8 y attenuated associations toward the null, suggesting associations are largely mediated by concurrent body fatness. Greater rates of weight-for-height change between 1 y and 10 y are consistently associated with adverse liver outcomes in adolescence. These associations are largely mediated through concurrent fatness. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  16. Increased metallothionein content in rat liver induced by x irradiation and exposure to high oxygen tension

    SciTech Connect

    Shiraishi, N.; Aono, K.; Utsumi, K.

    1983-08-01

    X irradiation and exposure to high oxygen tension are known to induce lipid peroxidation. The effects of these stresses on hepatic content of metallothionein, which may be involved in the regulation of zinc and copper metabolism, have been studied. The amount of metallothionein in rat liver was increased 11-fold by a high dose of X irradiation (1000 R). Increased metallothionein content (about 15 times) was also observed in liver of rats exposed to high oxygen tension for 3 days.

  17. Perinatal oxytocin increases the risk of offspring bipolar disorder and childhood cognitive impairment

    PubMed Central

    Freedman, David; Brown, Alan S.; Shen, Ling; Schaefer, Catherine A.

    2014-01-01

    Background We tested the hypothesis that perinatal oxytocin, given to pregnant women to induce labor, is related to offspring bipolar disorder (BP) and worse childhood cognitive performance among offspring. We also tested the association between childhood cognition and later BP. Methods A population-based birth cohort derived from the Child Health and Development Study (CHDS) which included nearly all pregnant women receiving obstetric care from the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) between1959–1966. Prospectively obtained medical and offspring cognitive performance were used. Potential cases with BP from the cohort were identified by database linkages. This protocol identified 94 cases who were matched 1:8 to controls. Results Perinatal oxytocin was associated with a 2.4 times increased odds of later BP. Oxytocin was also associated with decreased performance on the Raven Matrices, but not on the Peabody Picture Vocabulary Test (PPVT). Childhood cognition was not associated with later BP. Limitations Loss to follow-up must be considered in all birth cohort studies. Additionally, the childhood cognitive battery did not include tests related to multiple domains of cognition which have been associated with later BP. A third limitation is the modest sample size of those exposed to oxytocin. Conclusions This study provides evidence for a potentially important perinatal risk factor for BP and cognitive impairment in childhood. While the association between perinatal oxytocin and offspring BP must be viewed cautiously until further studies can attempt to replicate the result, it lends support to the broader view that neurodevelopmental factors contribute to BP. PMID:25462398

  18. Do gastrointestinal tract infections in infancy increase blood pressure in childhood? A cohort study.

    PubMed

    Martin, R M; Kramer, M S; Dahhou, M; Platt, R W; Patel, R; Bogdanovich, N; Matush, L; Davey Smith, G

    2010-12-01

    It has been hypothesised that dehydration in infancy could permanently increase sodium retention, raising blood pressure in later life. In this study, the association between gastrointestinal tract infection in infancy, a clinically relevant exposure often accompanied by dehydration, and raised blood pressure in childhood was investigated. Data from a cohort study nested within a cluster-randomised trial of breastfeeding promotion in the Republic of Belarus were analysed. 17 046 healthy breastfed infants were enrolled from 31 maternity hospitals. 13 889 (81.5%) children were followed-up at 6.5 years. Exposure measures were any gastrointestinal infection in infancy (to 1 year) and hospitalisations for gastrointestinal infection in infancy and in childhood (1-6.5 years). The outcomes were systolic and diastolic blood pressure at age 6.5 years. The prevalence of any gastrointestinal infection in infancy, and of hospitalisation for gastrointestinal infection in infancy or childhood, was 11.4%, 3.2% and 6.0%, respectively. No associations were observed between systolic blood pressure and any gastrointestinal infection (mean difference in those with minus those without infection -0.04 mm Hg; 95% CI -0.52 to 0.43) or hospitalisation for gastrointestinal infection (difference=-0.22 mm Hg; -1.07 to 0.64) in infancy. Nor were associations observed between diastolic blood pressure and any gastrointestinal infection during infancy or hospitalisation for gastrointestinal infection during infancy or childhood. No evidence was found to prove that hospitalisation for gastrointestinal infection in infancy or childhood leads to raised blood pressure at age 6.5 years in a developed country setting.

  19. Increasing the effective concentration of melphalan in experimental rat liver tumours: comparison of isolated liver perfusion and hepatic artery infusion.

    PubMed Central

    Marinelli, A.; van Dierendonck, J. H.; van Brakel, G. M.; Irth, H.; Kuppen, P. J.; Tjaden, U. R.; van de Velde, C. J.

    1991-01-01

    Regional chemotherapy allows further exploitation of the steep dose response curve of most chemotherapeutic agents, while systemic toxicity remains tolerable. We investigated the difference in maximally tolerated dose, pharmacokinetics and antitumour effect comparing administration of melphalan as a bolus in isolated liver perfusion (ILP) or via hepatic artery infusion (HAI). For these in vivo studies an experimental model for liver metastases in male WAG/Ola rats is obtained by subcapsular inoculation of CC531 rat colon carcinoma cells. In this system, ILP allowed administration of a two times higher dose than HAI (12 mg kg-1 vs 6 mg kg-1). In both treatment modalities systemic toxicity (leukopenia) was dose limiting. No hepatic toxicity was observed. Bolus administration of the maximally tolerated doses of melphalan in HAI (6 mg kg-1) and ILP (12 mg kg-1) resulted in four times higher concentrations in both liver and tumour tissue of the ILP treated rats. However, the ratio of mean drug concentration in liver vs tumour tissue appeared to be 1.5 times that found for HAI. In the range of the in tumour tissue measured melphalan concentrations the CC531 cells showed a steep dose response relationship in vitro. Whereas HAI resulted in significant tumour growth delay, complete remissions were observed in 90% of the rats treated with ILP. This study shows that with 12 mg kg-1 melphalan in ILP highly effective drug concentrations are achieved in CC531 tumour tissue; although the melphalan concentration in liver tissue shows an even higher increase than in tumour tissue, hepatic toxicity is negligible in this dose range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1764369

  20. Conivaptan increases serum sodium in hyponatremic patients with end-stage liver disease.

    PubMed

    O'Leary, Jacqueline G; Davis, Gary L

    2009-10-01

    Hyponatremia is associated with increased mortality in patients with end-stage liver disease and a greater risk of perioperative mortality with liver transplantation. We performed a retrospective review of our experience with conivaptan as a means of acutely increasing serum sodium in end-stage liver disease patients. The primary group consisted of 15 patients with end-stage liver disease who remained hyponatremic despite discontinuation of diuretics and a 1-L fluid restriction. Twenty milligrams of conivaptan was intravenously administered over 30 minutes, and this was followed by an infusion of 20 mg over 24 hours for 1 to 4 days. A second group of 9 hyponatremic end-stage liver disease patients was treated with 1-L fluid restriction and conivaptan while remaining on diuretics. In the group without diuretics, the mean serum sodium was 124 mmol/L 1 day before and on the day of conivaptan initiation, but the serum sodium rose to a mean of 127.7 mmol/L by day 1 and further increased to 128.6 mmol/L by the second day of the infusion. Despite the continuation of diuretics, the second group of 9 patients also had an increase in serum sodium from the day of conivaptan initiation (125.7 mmol/L) to 2 days after the treatment (130.6 mmol/L). Eleven patients underwent successful liver transplantation, 2 remained on the list for transplantation, and 11 were not candidates for transplantation and either died (7) or were discharged home and lost to follow-up (4). In conclusion, a short course of conivaptan increases serum sodium in patients with end-stage liver disease and may reduce the risk of proceeding to liver transplantation. Further study in a prospective clinical trial is needed to confirm safety and efficacy.

  1. Early behavioral inhibition and increased error monitoring predict later social phobia symptoms in childhood.

    PubMed

    Lahat, Ayelet; Lamm, Connie; Chronis-Tuscano, Andrea; Pine, Daniel S; Henderson, Heather A; Fox, Nathan A

    2014-04-01

    Behavioral inhibition (BI) is an early childhood temperament characterized by fearful responses to novelty and avoidance of social interactions. During adolescence, a subset of children with stable childhood BI develop social anxiety disorder and concurrently exhibit increased error monitoring. The current study examines whether increased error monitoring in 7-year-old, behaviorally inhibited children prospectively predicts risk for symptoms of social phobia at age 9 years. A total of 291 children were characterized on BI at 24 and 36 months of age. Children were seen again at 7 years of age, when they performed a Flanker task, and event-related potential (ERP) indices of response monitoring were generated. At age 9, self- and maternal-report of social phobia symptoms were obtained. Children high in BI, compared to those low in BI, displayed increased error monitoring at age 7, as indexed by larger (i.e., more negative) error-related negativity (ERN) amplitudes. In addition, early BI was related to later childhood social phobia symptoms at age 9 among children with a large difference in amplitude between ERN and correct-response negativity (CRN) at age 7. Heightened error monitoring predicts risk for later social phobia symptoms in children with high BI. Research assessing response monitoring in children with BI may refine our understanding of the mechanisms underlying risk for later anxiety disorders and inform prevention efforts. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. All rights reserved.

  2. Polμ deficiency increases resistance to oxidative damage and delays liver aging.

    PubMed

    Escudero, Beatriz; Lucas, Daniel; Albo, Carmen; Dhup, Suveera; Bacher, Jeff W; Sánchez-Muñoz, Aránzazu; Fernández, Margarita; Rivera-Torres, José; Carmona, Rosa M; Fuster, Encarnación; Carreiro, Candelas; Bernad, Raquel; González, Manuel A; Andrés, Vicente; Blanco, Luis; Roche, Enrique; Fabregat, Isabel; Samper, Enrique; Bernad, Antonio

    2014-01-01

    Polμ is an error-prone PolX polymerase that contributes to classical NHEJ DNA repair. Mice lacking Polμ (Polμ(-/-)) show altered hematopoiesis homeostasis and DSB repair and a more pronounced nucleolytic resection of some V(D)J junctions. We previously showed that Polμ(-/-) mice have increased learning capacity at old ages, suggesting delayed brain aging. Here we investigated the effect of Polμ(-/-) deficiency on liver aging. We found that old Polμ(-/-) mice (>20 month) have greater liver regenerative capacity compared with wt animals. Old Polμ(-/-) liver showed reduced genomic instability and increased apoptosis resistance. However, Polμ(-/-) mice did not show an extended life span and other organs (e.g., heart) aged normally. Our results suggest that Polμ deficiency activates transcriptional networks that reduce constitutive apoptosis, leading to enhanced liver repair at old age.

  3. Increased risk of antidepressant use in childhood cancer survivors: a Danish population-based cohort study.

    PubMed

    Lund, Lasse Wegener; Winther, J F; Cederkvist, L; Andersen, K K; Dalton, S O; Appel, C W; Rechnitzer, C; Schmiegelow, K; Johansen, C

    2015-03-01

    Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage to the National Prescription Drug Database, which worldwide is the oldest nationwide registry of prescription medication. Hazard ratios (HRs) for antidepressant use were estimated in a Cox proportional hazards model stratified on sex, with population comparisons as referents. Overall, childhood cancer survivors were at increased risk of having antidepressants prescribed (HR, 1.4; 95% confidence interval (CI), 1.3-1.5). The excess absolute risk of antidepressant use was 2.5 per 1000 person-years (95% CI, 1.7-3.3), equivalent to an excess of 2.5 survivors for every 100 survivors followed for 10years. Increased HRs of 30-50% were seen for survivors of cancers of all main groups (haematological malignancies, central nervous system (CNS) and solid tumors); the highest risk was among children treated with haematopoietic stem cell transplantation (HR, 1.9; 95% CI, 1.2-3.1). Our data suggested that the risk was most pronounced for children treated in the most recent calendar periods (test for interaction between cancer and calendar periods: P<0.001), especially for survivors of haematological cancers (P=0.007). Interaction analysis of the effect of parental socioeconomic position and psychiatric disease on the association between childhood cancer and antidepressant use indicated no modifying effect. Childhood cancer survivors should be followed-up for depression. Our results indicate an increasing need for follow-up especially in survivors treated by more recent, intensive anticancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Weight trajectories through infancy and childhood and risk of non-alcoholic fatty liver disease in adolescence: The ALSPAC study

    PubMed Central

    Anderson, Emma L.; Howe, Laura D.; Fraser, Abigail; Callaway, Mark P.; Sattar, Naveed; Day, Chris; Tilling, Kate; Lawlor, Debbie A.

    2014-01-01

    Background & Aims Adiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of infant and childhood adiposity with subsequent NAFLD risk. We examined associations of weight-for-height trajectories from birth to age 10 with liver outcomes in adolescence, and assessed the extent to which associations are mediated through fat mass at the time of outcome assessment. Methods Individual trajectories of weight and height were estimated for participants in the Avon Longitudinal Study of Parents and Children using random-effects linear-spline models. Associations of birthweight (adjusted for birth length) and weight change (adjusted for length/height change) from 0–3 months, 3 months–1 y, 1–3 y, 3–7 y, and 7–10 y with ultrasound scan (USS) determined liver fat and stiffness, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) at mean age 17.8 y were assessed with linear and logistic regressions. Mediation by concurrent fat mass was assessed with adjustment for fat mass at mean age 17.8 y. Results Birth weight was positively associated with liver stiffness and negatively with ALT and AST. Weight change from birth to 1 y was not associated with outcomes. Weight change from 1–3 y, 3–7 y, and 7–10 y was consistently positively associated with USS and blood-based liver outcomes. Adjusting for fat mass at mean age 17.8 y attenuated associations toward the null, suggesting associations are largely mediated by concurrent body fatness. Conclusions Greater rates of weight-for-height change between 1 y and 10 y are consistently associated with adverse liver outcomes in adolescence. These associations are largely mediated through concurrent fatness. PMID:24768828

  5. Liver surgery in the presence of cirrhosis or steatosis: Is morbidity increased?

    PubMed Central

    McCormack, Lucas; Capitanich, Pablo; Quiñonez, Emilio

    2008-01-01

    Background data The prevalence of steatosis and hepatitis-related liver cirrhosis is dramatically increasing together worldwide. Cirrhosis and, more recently, steatosis are recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection when compared with patients with healthy liver. Objective To review present knowledge regarding how the presence of cirrhosis or steatosis can influence postoperative outcome after liver resection. Methods A critical review of the English literature was performed to provide data concerning postoperative outcome of patients presenting injured livers who required hepatectomy. Results In clinical studies, the presence of steatosis impaired postoperative outcome regardless the severity and quality of the hepatic fat. A great improvement in postoperative outcome has been achieved using modern and multidisciplinary preoperative workup in cirrhotic patients. Due to the lack of a proper classification for morbidity and a clear definition of hepatic failure in the literature, the comparison between different studies is very limited. Although, many surgical strategies have been developed to protect injured liver surgery, no one have gained worldwide acceptance. Conclusion Surgeons should take the presence of underlying injured livers into account when planning the extent and type of hepatic surgery. Preoperative and perioperative interventions should be considered to minimize the additional damage. Further randomized trials should focus on the evaluation of novel preoperative strategies to minimize risk in these patients. Each referral liver center should have the commitment to report all deaths related to postoperative hepatic failure and to use a common classification system for postoperative complications. PMID:18439273

  6. Obesity Increases Sensitivity to Endotoxin Liver Injury: Implications for the Pathogenesis of Steatohepatitis

    NASA Astrophysics Data System (ADS)

    Yang, Shi Qi; Zhi Lin, Hui; Lane, M. Daniel; Clemens, Mark; Diehl, Anna Mae

    1997-03-01

    Genetically obese fatty/fatty rats and obese/obese mice exhibit increased sensitivity to endotoxin hepatotoxicity, quickly developing steatohepatitis after exposure to low doses of lipopolysaccharide (LPS). Among obese animals, females are more sensitive to endotoxin liver injury than males. LPS induction of tumor necrosis factor α (TNFα ), the proven affecter of endotoxin liver injury, is no greater in the livers, white adipose tissues, or sera of obese animals than in those of lean controls. Indeed, the lowest serum concentrations of TNF occur in female obese rodents, which exhibit the most endotoxin-induced liver injury. Several cytokines that modulate the biological activity of TNF are regulated abnormally in the livers of obese animals. After exposure to LPS, mRNA of interferon γ , which sensitizes hepatocytes to TNF toxicity, is overexpressed, and mRNA levels of interleukin 10, a TNF inhibitor, are decreased. The phagocytic activity of liver macrophages and the hepatic expression of a gene encoding a macrophage-specific receptor are also decreased in obesity. This new animal model of obesity-associated liver disease demonstrates that hepatic macrophage dysfunction occurs in obesity and suggests that this might promote steatohepatitis by sensitizing hepatocytes to endotoxin.

  7. Vitamin A supplementation and increased prevalence of childhood diarrhoea and acute respiratory infections.

    PubMed

    Stansfield, S K; Pierre-Louis, M; Lerebours, G; Augustin, A

    1993-09-04

    There is uncertainty over whether vitamin A supplementation reduces morbidity among children with subclinical deficiency of the vitamin. Hence a double-blind, placebo-controlled trial of the effect of vitamin A supplementation on childhood morbidity was conducted among 11,124 children aged 6-83 months in the northwest of Haiti. After a random start, children were sequentially assigned by household units to receive either megadose vitamin A or placebo in three distribution cycles 4 months apart. 2 to 8 weeks after each administration of the vitamin A and placebo capsules, indicators of childhood morbidity were reassessed through interviews conducted in the homes of participating families. The vitamin A group was found to have an increased 2-week prevalence of all symptoms and signs of childhood morbidity assessed, including diarrhoea (rate ratio [RR] = 1.09, 95% confidence interval 1.05-1.14), rhinitis (RR = 1.02, 95% confidence interval 1.00-1.04), cold/flu symptoms (RR = 1.04, 95% confidence interval 1.01-1.06), cough (RR = 1.07, 95% confidence interval 1.03-1.11), and rapid breathing (RR = 1.18, 95% confidence interval 1.09-1.27). The study shows an increased 2-week prevalence of diarrhoea and the symptoms of respiratory infections after vitamin A supplementation.

  8. Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer

    ClinicalTrials.gov

    2015-05-14

    Childhood Hepatocellular Carcinoma; Papillary Thyroid Cancer; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Thyroid Cancer; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

  9. Childhood Abuse, Nonadherence, and Medical Outcome in Pediatric Liver Transplant Recipients

    ERIC Educational Resources Information Center

    Shemesh, Eyal; Annunziato, Rachel A.; Yehuda, Rachel; Shneider, Benjamin L.; Newcorn, Jeffrey H.; Hutson, Carolyn; Cohen, Judith A.; Briere, John; Gorman, Jack M.; Emre, Sukru

    2007-01-01

    Objective: The study assessed the relationship between a history of child abuse, nonadherence to medications, and medical outcome in children who had a liver transplant. Method: Abuse history for children and adolescents ages 8 to 21 who underwent a liver transplantation at Mount Sinai Medical Center in New York was obtained in interviews in 2002.…

  10. Childhood Abuse, Nonadherence, and Medical Outcome in Pediatric Liver Transplant Recipients

    ERIC Educational Resources Information Center

    Shemesh, Eyal; Annunziato, Rachel A.; Yehuda, Rachel; Shneider, Benjamin L.; Newcorn, Jeffrey H.; Hutson, Carolyn; Cohen, Judith A.; Briere, John; Gorman, Jack M.; Emre, Sukru

    2007-01-01

    Objective: The study assessed the relationship between a history of child abuse, nonadherence to medications, and medical outcome in children who had a liver transplant. Method: Abuse history for children and adolescents ages 8 to 21 who underwent a liver transplantation at Mount Sinai Medical Center in New York was obtained in interviews in 2002.…

  11. Changes in childhood food consumption patterns: a cause for concern in light of increasing body weights.

    PubMed

    St-Onge, Marie-Pierre; Keller, Kathleen L; Heymsfield, Steven B

    2003-12-01

    Childhood obesity is currently at its highest: recent statistics show that 16% of children between the ages of 6 and 11 y are overweight [> or =95th percentile of body mass index (BMI; in kg/m(2)) for age] and that an additional 14.3% are at risk of becoming overweight (> or =85th percentile but < 95th percentile of BMI for age). As children's body weights have increased, so has their consumption of fast foods and soft drinks. The proportion of foods that children consumed from restaurants and fast food outlets increased by nearly 300% between 1977 and 1996. Children's soft drink consumption has also increased during those years, and now soft drinks provide soft drink consumers 188 kcal/d beyond the energy intake of nonconsumers. These changes in food intakes among children may partly explain the rise in childhood obesity observed in the past few years. Although the mechanism of appetite regulation will not be explored in this report, it is hypothesized that the greater energy intakes in children who consume large amounts of soft drinks and fast foods are not compensated for by increased physical activity or decreased energy intakes. Furthermore, overweight and obesity in childhood may predispose persons to morbidity in adulthood. Blood pressure and fasting insulin and cholesterol concentrations are higher in overweight children than in normal-weight children. This review focuses on current food patterns and eating habits of children, in an attempt to explain their increasing BMI. In addition, a critical review of food service and political practices regarding food choices for children at school is included.

  12. Paradoxical increase in liver ketogenesis during long-term insulin-induced hypoglycemia in diabetic rats.

    PubMed

    Schiavon, Fabiana P M; Gazola, Vilma A F G; Furlan, Maria M D P; Barrena, Helenton C; Bazotte, Roberto B

    2011-02-01

    It is well established that insulin inhibits liver ketogenesis. However, during insulin-induced hypoglycemia (IIH) the release of counterregulatory hormones could overcome the insulin effect on ketogenesis. To clarify this question the ketogenic activity in livers from alloxan-diabetic rats submitted to long-term IIH was investigated. Moreover, liver glycogenolysis, gluconeogensis, ureagenesis and the production of L-lactate were measured, and its correlation with blood levels of ketone bodies (KB), L-lactate, glucose, urea and ammonia was investigated. For this purpose, overnight fasted alloxan-diabetic rats (DBT group) were compared with control non-diabetic rats (NDBT group). Long-term IIH was obtained with an intraperitoneal injection of Detemir insulin (1 U/kg), and KB, glucose, L-lactate, ammonia and urea were evaluated at 0, 2, 4, 6, 8 or 10 h after insulin injection. Because IIH was well established two hours after insulin injection this time was used for liver perfusion experiments. The administration of Detemir insulin decreased (P < 0.05) blood KB and glucose levels, but there was an increase in the blood L-lactate levels and a rebound increase in blood KB during the glucose recovery phase of IIH. In agreement with these results, the capacity to produce KB from octanoate was increased in the livers of DBT rats. Moreover, the elevated blood L-lactate levels in DBT rats could be attributed to the higher (P < 0.05) glycogenolysis when part of glucose from glycogenolysis enters glycolysis, producing L-lactate. In contrast, except glycerol, gluconeogenesis was negligible in the livers of DBT rats. Therefore, during long-term IIH the higher liver ketogenic capacity of DBT rats increased the risk of hyperketonemia. In addition, in spite of the fact that the insulin injection decreased blood KB, there was a risk of worsening lactic acidosis.

  13. Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease.

    PubMed

    Reilly, Norelle R; Lebwohl, Benjamin; Hultcrantz, Rolf; Green, Peter H R; Ludvigsson, Jonas F

    2015-06-01

    Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  14. Increased in vitro phosphorylation of rat liver nucleolar proteins following triiodothyronine administration.

    PubMed

    Fugassa, E; Gallo, G; Pertica, M

    1976-11-15

    It has been shown that triiodothyronine (Ta) administration to thyroidectomized rats induces an increase in the in vitro net 32P uptake into liver nucleolar proteins. Such an increase depends on a stimulation of the nucleolus-associated protein kinase activity and not on a lower dephosphorylation rate.

  15. [A 56-year-old female patient with Raynaud's syndrome, increased liver enzymes and neuropsychiatric symptoms].

    PubMed

    Hass, H G; Kaiser, S

    2006-10-06

    A 56-year-old woman presented with increased liver enzymes (GPT, GOT), arthralgias, Raynaud's syndrome and disturbance of sleep and concentration. Serology and liver biopsy indicated chronic hepatitis C infection (HCV) and viral-induced liver cirrhosis with unremarkable liver synthesizing parameters. An HCV-triggered cryoglobinemia was excluded, but high elevated antinuclear antibodies (ANA) and anti-RNP autoantibodies, typical serological parameters of mixed tissue collagenous (Sharp}s disease), were detectable. Magnetic resonance spectroscopy (H-MRS) was performed to differentiate between cerebral vasculitis and mild hepatic encephalopathy. This detected abnormal pattern of cerebral metabolites (myo-inositol and choline), is specific for HE. After onset of an antiviral therapy (terferon/ribavirin), low protein diet with supplementation of l-ornithine-l-aspartate the arthralgia and neuropsychiatric symptoms rapidly improved and HCV-RNA PCR became negative. Unfortunately, after cessation of antiviral treatment the patient had a relapse of HCV with a worsening of the arthralgia and the Raynaud symptoms (HCV-triggered Sharp}s disease). Even in patients with mildly abnormal liver function and liver cirrhosis it is important to consider (mild) hepatic encephalopathy if neuropsychiatric symptoms occur.

  16. Increased Th17 cells contribute to disease progression in patients with HBV-associated liver cirrhosis.

    PubMed

    Sun, H Q; Zhang, J Y; Zhang, H; Zou, Z S; Wang, F S; Jia, J H

    2012-06-01

    T helper (Th) 17 cells have been demonstrated to participate in the pathogenesis of HBV-associated liver damage. However, little is known regarding the immunopathogenic role of liver fibrosis in patients with HBV-associated liver cirrhosis. The aims of this study were to evaluate whether Th17 cells are related to disease progression in patients and to explore the possible mechanisms. The frequencies of circulating Th17 cells were analysed in 78 patients with hepatitis B and cirrhosis (Child A: 34; Child B: 22; Child C 22) and matched controls. Liver samples were collected from 13 patients with HBV-associated cirrhosis, 23 patients with chronic hepatitis B and 12 healthy controls for immunohistochemical analysis. IL-17 receptor expression was studied on liver biopsies and in human hepatic stellate cells as well as their response to recombinant IL-17 by flow cytometry. Patients with hepatitis B-associated cirrhosis with more severe disease displayed significant increases in peripheral numbers of Th17 cells as well as in IL-17 plasma levels. The increased intrahepatic IL-17(+) cells correlated positively with fibrotic staging scores and clinical progression from CHB to cirrhosis. Moreover, many IL-17(+) cells were located in fibrotic areas in the liver of patients with cirrhosis. In vitro, IL-17 together with IL-17-activated monocytes, could promote the activation of stellate cells, which, in turn, aggravated liver fibrosis and the inflammatory response. In summary, increased peripheral and intrahepatic Th17 cells are enriched in patients with hepatitis B and cirrhosis and contribute further to the severity of disease progression through induction of stellate cell activation.

  17. Liver volume and hepatic adiposity in childhood: relations to body growth and visceral fat.

    PubMed

    Malpique, R; Bassols, J; López-Bermejo, A; Diaz, M; Villarroya, F; Pavia, J; Congo, A; de Zegher, F; Ibáñez, L

    2017-08-14

    The sequence of prenatal growth restraint and postnatal catch-up growth may lead to hepato-visceral adiposity, insulin resistance and low-grade inflammation before the onset of puberty. In prepubertal children born appropriate for gestational age (AGA) or small for gestational age (SGA), we assessed potential relationships between the aforementioned sequence and liver volume. The study population consisted of 86 children (41 AGA and 45 SGA with catch-up growth; age (mean±s.e.m.), 8.5±0.1 years), recruited into two prospective longitudinal studies. Anthropometry, endocrine-metabolic variables and inflammatory and hepatic markers were assessed, along with liver volume, hepatic adiposity and abdominal fat partitioning (by magnetic resonance imaging). AGA and SGA children differed in hepato-visceral adiposity, but had similar liver volumes. Boys had larger livers than girls, and higher sex hormone binding globulin and inflammation markers. Liver volume correlated with height Z-score, body mass index Z-score, HOMA-IR (homeostasis model assessment-insulin resistance) and with subcutaneous and visceral fat, but not with birth weight Z-score or with hepatic adiposity. Height, visceral fat, gender and HOMA-IR were major determinants of liver volume, together explaining 61% of its variance. The trajectory from prenatal restraint, via postnatal catch-up, to hepato-visceral adiposity and insulin resistance does not appear to be detectably influenced by prepubertal alterations of liver volume. Further follow-up will disclose the potential role of liver volume in the pubertal segment of this trajectory, and whether the augmented fat content and visceral adiposity in SGA subjects is followed by the development of metabolic syndrome and hepatic dysfunction in adulthood.International Journal of Obesity advance online publication, 19 September 2017; doi:10.1038/ijo.2017.198.

  18. Myeloid deletion of nuclear factor erythroid 2-related factor 2 increases atherosclerosis and liver injury.

    PubMed

    Collins, Alan R; Gupte, Anisha A; Ji, Ruirui; Ramirez, Maricela R; Minze, Laurie J; Liu, Joey Z; Arredondo, Magda; Ren, Yuelan; Deng, Tuo; Wang, Jun; Lyon, Christopher J; Hsueh, Willa A

    2012-12-01

    To determine the impact of hematopoietic deletion of nuclear factor- (erythroid-derived 2) like 2 factor (Nrf2) on the development of atherosclerosis and liver injury in an obese, hypercholesterolemic mouse model. Two-month-old male low-density lipoprotein receptor-deficient mice were lethally irradiated and transplanted with either wild type or Nrf2-deficient (Nrf2(-/-)) bone marrow cells. At 3 months of age, mice were placed on an obesogenic high-fat diet (HFD), high-cholesterol diet for 7 months. Despite no differences in body weight, body fat percentage, liver fat, plasma glucose, lipids, or insulin, the HFD-fed Nrf2(-/-) bone marrow recipients had increased proinflammatory vascular gene expression, a significant increase in atherosclerosis area (18% versus 28%; P=0.018) and lesion complexity, and a marked increase in liver fibrosis. The acceleration of vascular and liver injury may arise from enhanced macrophage migration, inflammation, and oxidative stress resulting from myeloid Nrf2 deficiency. Myeloid-derived Nrf2 activity attenuates atherosclerosis development and liver inflammation and fibrosis associated with obesity. Prevention of oxidative stress in macrophage and other myeloid lineage cells may be an important therapeutic target to reduce inflammation-driven complications of obesity.

  19. Increased expression of Zinc finger protein 267 in non-alcoholic fatty liver disease

    PubMed Central

    Schnabl, Bernd; Czech, Barbara; Valletta, Daniela; Weiss, Thomas S; Kirovski, Georgi; Hellerbrand, Claus

    2011-01-01

    Hepatocellular lipid accumulation is a hallmark of non-alcoholic fatty liver disease (NAFLD), which encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and ultimately cirrhosis. Zinc finger protein 267 (ZNF267) belongs to the family of Kruppel-like transcription factors, which regulate diverse biological processes that include development, proliferation, and differentiation. We have previously demonstrated that ZNF267 expression is up-regulated in liver cirrhosis and is further increased in hepatocellular carcinoma (HCC). Here, we analyzed the expression of ZNF267 in tissue specimens of NAFLD patients and found a significant up-regulation compared to normal liver tissue. Noteworthy, ZNF267 mRNA was already significantly increased in steatotic liver tissue without inflammation. In line with this, incubation of primary human hepatocytes with palmitic acid induced a dose-dependent lipid accumulation and corresponding dose-dependent ZNF267 induction in vitro. Furthermore, hepatocellular lipid accumulation induced formation of reactive oxygen species (ROS), and also chemically induced ROS formation increased ZNF267 mRNA expression. In summary with previous findings, which revealed ZNF267 as pro-fibrogenic and pro-cancerogenic factor in chronic liver disease, the present study further suggests ZNF267 as promising therapeutic target particularly for NAFLD patients. In addition, it further indicates that hepatic steatosis per se has pathophysiological relevance and should not be considered as benign. PMID:22076166

  20. Childhood maltreatment is associated with increased risk of subclinical hypothyroidism in pregnancy.

    PubMed

    Moog, Nora K; Heim, Christine M; Entringer, Sonja; Kathmann, Norbert; Wadhwa, Pathik D; Buss, Claudia

    2017-10-01

    The critical importance of thyroid hormones for fetal development is well established. The developing fetus is dependent on the mother for adequate thyroid hormone supply, and maternal thyroid dysfunction in pregnancy may result in suboptimal fetal development. Because exposure to childhood maltreatment (CM) has been associated with thyroid dysfunction in the non-pregnant state, we sought to test the hypothesis that exposure to CM may represent a risk factor for the development of maternal hypothyroidism in pregnancy. The study was conducted in a healthy cohort of 102 pregnant mothers who were followed across the entire course of pregnancy. At each trimester thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were measured in maternal serum. Experience of CM was assessed using the Childhood Trauma Questionnaire. After adjusting for potentially confounding variables, CM exposure was associated with increased TSH concentrations across pregnancy (F1,94.6=11.52, p=0.001) and with a 4- to 7-fold increased risk of TSH levels above the trimester-specific clinical cut-off values. Women with clinically elevated TSH concentrations did not differ in fT4 concentrations from women with normal TSH concentrations (p>0.1), suggesting subclinical hypothyroidism. Our findings suggest that there is a substantial and clinically relevant increased risk for thyroid dysfunction during pregnancy among women exposed to abuse or neglect in their childhood. This could potentially have adverse consequences for fetal brain development. Thus, these findings highlight the critical importance of considering CM exposure as a potential risk factor for (subclinical) hypothyroidism in pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. [An increase in allergic diseases in childhood--current hypotheses and possible prevention].

    PubMed

    Kurz, Herbert; Riedler, Jose

    2003-01-01

    During the last few decades there has ben a significant rise in the prevalence of allergic diseases such as asthma, hay fever and atopic dermatitis. Epidemiological studies strongly suggest that this increase is real and not due to changes in diagnostic labelling. It has become increasingly clear that a complex interplay between genetic and environmental factors account for this phenomenon. Genetically predisposed individuals are at an increased susceptibility to develop asthma or other allergic diseases when exposed to certain environmental or lifestyle factors. Particularly passive smoking has been shown to increase the risk for asthma in many studies and for atopy at least in some studies. This association is less clear for the exposure to sulfur dioxide, particulate matter, diesel exhaust and ozone. Lifestyle factors like socioeconomic status, sib-ship size, early childhood infections, dietary habits, growing up in antroposophic families or on a farm are more and more realised to be of great relevance for the development of allergic conditions. At the moment, there is a lot of uncertainty about which recommendations should be given for primary prevention. Recent studies have challenged the old paradigma that avoidance of early allergen contact could prevent the development of allergic disease. However, there is consensus that avoidance of smoking during pregnancy and avoidance of passive smoking during childhood should be recommended for primary prevention of asthma.

  2. Fatty Liver, Insulin Resistance, and Obesity: Relationships With Increase in Coronary Artery Calcium Over Time.

    PubMed

    Sung, Ki-Chul; Ryu, Seungho; Lee, Jong-Young; Lee, Sung Ho; Cheong, Eun Sun; Wild, Sarah H; Byrne, Christopher D

    2016-06-01

    Nonalcoholic fatty liver disease, insulin resistance (IR), and obesity frequently coexist with type 2 diabetes mellitus (DM), but it is uncertain whether these risk factors for vascular disease contribute to a change in atherosclerosis over time, independently of DM status. We hypothesized that the combination of fatty liver, IR, and obesity would be associated with an increase in coronary artery calcium (CAC) score over time, independently of DM status, other cardiovascular risk factors, and medications. Data were analyzed from a South Korean occupational cohort of 2175 people. The outcome was increase in cardiac computed tomography CAC score between baseline and follow-up. Insulin resistance was defined by homeostatic model assessment of insulin resistance (HOMA-IR) ≥75th percentile and fatty liver by ultrasound. In 592 (27.2%) participants, CAC score increased from baseline (mean ± SD; mean age at baseline, 44.8 ± 5.5 years); and in 1583 subjects, CAC did not change or improved during follow-up (mean age, 41.6 ± 5.6 years). Diabetes mellitus, HOMA-IR, fatty liver, and obesity prevalence were all higher (all P < 0.001) in participants whose CAC score increased from baseline. Adjusting for DM and potential confounders, the combination of IR, obesity, and fatty liver was independently associated with increase in CAC score over time (hazard ratio: 2.46, 95% confidence interval: 1.50-4.03). The combination of fatty liver, IR, and obesity is associated with progression of atherosclerosis over time independently of DM, cardiovascular risk factors, and all medications for cardiovascular disease and DM. © 2016 Wiley Periodicals, Inc.

  3. Liver grafts procured from donors after circulatory death have no increased risk of microthrombi formation.

    PubMed

    Verhoeven, Cornelia J; Simon, Tiarah C; de Jonge, Jeroen; Doukas, Michael; Biermann, Katharina; Metselaar, Herold J; Ijzermans, Jan N M; Polak, Wojciech G

    2016-12-01

    Microthrombi formation provoked by warm ischemia and vascular stasis is thought to increase the risk of nonanastomotic strictures (NAS) in liver grafts obtained by donation after circulatory death (DCD). Therefore, potentially harmful intraoperative thrombolytic therapy has been suggested as a preventive strategy against NAS. Here, we investigated whether there is histological evidence of microthrombi formation during graft preservation or directly after reperfusion in DCD livers and the development of NAS. Liver biopsies collected at different time points during graft preservation and after reperfusion were triple-stained with hematoxylin-eosin (H & E), von Willebrand factor VIII (VWF), and Fibrin Lendrum (FL) to evaluate the presence of microthrombi. In a first series of 282 sections obtained from multiple liver segments of discarded DCD grafts, microthrombi were only present in 1%-3% of the VWF stainings, without evidence of thrombus formation in paired H & E and FL stainings. Additionally, analysis of 132 sections obtained from matched, transplanted donation after brain death and DCD grafts showed no difference in microthrombi formation (11.3% versus 3.3% respectively; P = 0.082), and no relation to the development of NAS (P = 0.73). Furthermore, no microthrombi were present in perioperative biopsies in recipients who developed early hepatic artery thrombosis. Finally, the presence of microthrombi did not differ before or after additional flushing of the graft with preservation solution. In conclusion, the results of our study derogate from the hypothesis that DCD livers have an increased tendency to form microthrombi. It weakens the explanation that microthrombi formation is a main causal factor in the development of NAS in DCD and that recipients could benefit from intraoperative thrombolytic therapy to prevent NAS following liver transplantation. Liver Transplantation 22 1676-1687 2016 AASLD.

  4. Splenectomy Correlates With Increased Risk of Pyogenic Liver Abscess: A Nationwide Cohort Study in Taiwan

    PubMed Central

    Lai, Shih-Wei; Lai, Hsueh-Chou; Lin, Cheng-Li; Liao, Kuan-Fu

    2015-01-01

    Objectives Little is known about the risk of pyogenic liver abscess in patients with splenectomy. We explored the relationship between splenectomy and pyogenic liver abscess in Taiwan. Methods We conducted a nationwide cohort analysis using the hospitalization dataset of the Taiwan National Health Insurance Program. We included 17 779 subjects aged 20–84 years who underwent splenectomy in 1998 to 2010 (splenectomy group) and 70 855 randomly selected subjects without splenectomy (non-splenectomy group). Both groups were matched by sex, age, other comorbidities, and hospitalization year of receiving splenectomy. The incidence of pyogenic liver abscess at the end of 2011 was measured. The multivariable Cox proportional hazard regression model was used to estimate the hazard ratios and 95% confidence intervals for pyogenic liver abscess associated with splenectomy and other comorbidities. Results The overall incidence rate was 3.75-fold higher in the splenectomy group than that in the non-splenectomy group (2.15 vs 0.57 per 1000 person-years; 95% confidence interval, 3.57–3.94). After controlling for potential confounding factors, the adjusted hazard ratio of pyogenic liver abscess was 3.89 in subjects with splenectomy (95% confidence interval, 3.20–4.72) when compared with subjects without splenectomy. In further analysis, the hazard ratio markedly increased to 14.34 for those with splenectomy and having any of the assessed comorbidities, including alcoholism, biliary stone, chronic kidney disease, chronic liver diseases, and diabetes mellitus (95% confidence interval, 10.61–19.39). Conclusions Patients with splenectomy are at an increased risk of developing pyogenic liver abscess, particularly when they have comorbid conditions. PMID:26256773

  5. Increasing prevalence of childhood overweight and obesity in a coastal province in China.

    PubMed

    Zhang, Y; Zhao, J; Chu, Z; Zhou, J

    2016-12-01

    The increasing prevalence of childhood obesity constitutes a serious public health problem in both developed and developing countries. The present study examined the prevalent trends in overweight and obesity among children and adolescents in Shandong, China spanning 29 years (1985-2014). Data for this study were obtained from four cross-sectional surveys of schoolchildren carried out in 1985, 1995, 2005 and 2014 in Shandong Province, China. A total of 39 943 students aged 7-18 years were included in this study (14 458 in 1985, 7 198 in 1995, 8 568 in 2005 and 9 719 in 2014). Using IOTF criteria, the prevalence of overweight and obesity increased from 1.73% and 0.05% for boys, 1.67% and 0.04% for girls in 1985 to 20.83% and 10.39% for boys, 15.81% and 4.35% for girls in 2014; Using World Health Organization criteria, the prevalence of overweight and obesity increased from 2.76% and 0.45% for boys, 2.46% and 0.11% for girls in 1985 to 20.30% and 18.16% for boys, 18.89% and 6.58% for girls in 2014, respectively. Childhood overweight and obesity has entered the extensively epidemic stage in this region at present. Comprehensive strategies of intervention should include periodical monitoring, education on pattern of nutrition, oxygen-consuming physical exercises and healthy dietary behaviour. © 2015 World Obesity Federation.

  6. Nicotine increases hepatic oxygen uptake in the isolated perfused rat liver by inhibiting glycolysis.

    PubMed

    Dewar, Brian J; Bradford, Blair U; Thurman, Ronald G

    2002-06-01

    Nicotine influences energy metabolism, yet mechanisms remain unclear. Since the liver is one of the largest organs and performs many metabolic functions, the goal of this study was to determine whether nicotine would affect respiration and other metabolic functions in the isolated perfused liver. Infusion of 85 microM nicotine caused a rapid 10% increase in oxygen uptake over basal values of 105 +/- 5 micromol/g/h in perfused livers from fed rats, and an increase of 27% was observed with 850 microM nicotine. Concomitantly, rates of glycolysis of 105 +/- 8 micromol/g/h were decreased to 52 +/- 9 micromol/g/h with nicotine, whereas ketone body production was unaffected. Nicotine had no effect on oxygen uptake in glycogen-depleted livers from 24-h fasted rats. Furthermore, addition of glucose to perfused livers from fasted rats partially restored the stimulatory effect of nicotine. Infusion of atractyloside, potassium cyanide, or glucagon blocked the nicotine-induced increase in respiration. Intracellular calcium was increased in isolated hepatocytes by nicotine, a phenomenon prevented by incubation of cells with d-tubocurarine, a nicotinic acetylcholine receptor antagonist. Respiration was also increased approximately 30% in hepatocytes isolated from fed rats by nicotine, whereas hepatocytes isolated from fasted rats showed little response. In the presence of N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), an inhibitor of cyclic AMP-dependent protein kinase A, nicotine failed to stimulate respiration. These data support the hypothesis that inhibition of glycolysis by nicotine increases oxygen uptake due to an ADP-dependent increase in mitochondrial respiration.

  7. PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease.

    PubMed

    Salameh, Habeeb; Masadeh, Maen; Al Hanayneh, Muhannad; Petros, Vincent; Maslonka, Matthew; Nanda, Arjun; Singal, Ashwani K

    2016-12-18

    To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms. Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients.

  8. α-SMA overexpression associated with increased liver fibrosis in infants with biliary atresia.

    PubMed

    Dong, Rui; Luo, Yi; Zheng, Shan

    2012-12-01

    The mechanisms responsible for increased collagen production and hepatic fibrosis in biliary atresia (BA) remain largely unknown. We evaluated α-smooth muscle actin (α-SMA) expression in liver and the porta hepatis in infants with BA. Immunohistochemical staining for α-SMA and CD68 in the BA liver and porta hepatis was performed. A semiquantitative 3-grade staging system was employed to estimate liver fibrosis. The densities of CD68 in BA liver and the levels of direct bilirubin were assessed in relation to α-SMA expression. α-SMA was found to be overexpressed in epithelial cells and in periductular collagen fibers. The expression in infants with BA was higher than that in the control group (P < 0.05). The amount of α-SMA in BA was positively correlated with liver fibrosis scores (r = 0.549, P = 0.022). The levels of α-SMA in the liver of BA were negatively related with improvements in direct bilirubin levels, 3 months postoperatively (r = -0.653, P = 0.029). The correlation between the α-SMA and CD-68 expression was not significantly different (r = 0.444, P = 0.057). The expression of α-SMA in BA liver is higher than that in contro1 group. α-SMA expression is negatively correlated with the reduction of direct bilirubin, 3 months postoperatively, probably due to fibrosis or cirrhosis affecting the entire biliary system.

  9. PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease

    PubMed Central

    Salameh, Habeeb; Masadeh, Maen; Al Hanayneh, Muhannad; Petros, Vincent; Maslonka, Matthew; Nanda, Arjun; Singal, Ashwani K

    2016-01-01

    AIM To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. METHODS Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms. RESULTS Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. CONCLUSION PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients. PMID:28050240

  10. Do Single Experiences of Childhood Abuse Increase Psychopathology Symptoms in Adulthood?

    PubMed

    Rehan, Wail; Antfolk, Jan; Johansson, Ada; Santtila, Pekka

    2016-05-03

    Experiencing emotional, physical, and/or sexual abuse in childhood increases the risk (compared with baseline) of developing psychopathological symptoms in adulthood. In the present study, we explored the effects of experiencing only a single abusive event on adulthood psychopathology, and compared this with the risk in individuals with no abusive experiences and with the risk in individuals with several abusive experiences. We used a Finnish population-based sample of 10,980 adult participants (3,766 male and 7,214 female twins and their siblings). The participants reported abuse experiences using the Childhood Trauma Questionnaire (CTQ) and current psychopathology symptoms using the depression and anxiety scales of the Brief Symptom Inventory-18 (BSI-18). We found that in both men and women even single experiences of emotional and sexual abuse were associated with increased psychopathology symptoms compared with no abuse experiences. Single experiences of physical abuse did not, however, increase the risk in either women or men. As expected, experiences of repeated abuse (of all abuse types) increased the risk of psychopathology symptoms compared with experiences of single abuse. When we isolated individuals who only had a single experience of any type of abuse (i.e., emotional, physical, or sexual) to control for possible co-morbidity, no increased risk was found. This study shows that individuals who report experiencing single events of abuse of a specific abuse type have an increased risk of displaying psychopathology symptoms in adulthood. This increase is, however, mainly due to co-morbidity of abuse types.

  11. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

    PubMed

    Bjursell, Mikael; Wedin, Marianne; Admyre, Therése; Hermansson, Majlis; Böttcher, Gerhard; Göransson, Melker; Lindén, Daniel; Bamberg, Krister; Oscarsson, Jan; Bohlooly-Y, Mohammad

    2013-01-01

    Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH) and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  12. Erythropoietin administration increases splenic erythroferrone protein content and liver TMPRSS6 protein content in rats.

    PubMed

    Gurieva, Iuliia; Frýdlová, Jana; Rychtarčíková, Zuzana; Vokurka, Martin; Truksa, Jaroslav; Krijt, Jan

    2017-02-28

    Erythroferrone (ERFE) and TMPRSS6 are important proteins in the regulation of iron metabolism. The objective of the study was to examine splenic ERFE and liver TMPRSS6 synthesis in rats treated with a combination of iron and erythropoietin (EPO). EPO was administered to female Wistar rats at 600U/day for four days, iron-pretreated rats received 150mg of iron before EPO treatment. Content of ERFE and TMPRSS6 proteins was determined by commercial antibodies. Iron pretreatment prevented the EPO-induced decrease in hepcidin expression. Content of phosphorylated SMAD 1,5,8 proteins was decreased in the liver by both EPO and iron plus EPO treatment. Fam132b expression in the spleen was increased both by EPO and iron plus EPO treatments; these treatments also significantly induced splenic Fam132a expression. ERFE protein content in the spleen was increased both by EPO and iron plus EPO to a similar extent. EPO administration increased TMPRSS6 content in the plasma membrane-enriched fraction of liver homogenate; in iron-pretreated rats, this increase was abolished. The results confirm that iron pretreatment prevents the EPO-induced decrease in liver Hamp expression. This effect probably occurs despite high circulating ERFE levels, since EPO-induced ERFE protein synthesis is not influenced by iron pretreatment.

  13. Severe Sarcopenia and Increased Fat Stores in Pediatric Patients With Liver, Kidney, or Intestine Failure.

    PubMed

    Mangus, Richard S; Bush, Weston J; Kubal, Chandrashekhar A; Miller, Christina

    2017-06-09

    Malnutrition and wasting predict clinical outcomes in children with severe chronic illness. Objectively calculated malnutrition in children with end-stage organ failure has not been well studied. This analysis compares children with kidney, liver or intestine failure to healthy controls to quantitate the disparity in muscle and fat stores. Children younger than age 19 with end stage liver, kidney or intestine failure and with pre-transplant computed tomography (CT) imaging were selected from the transplant database. Age and gender-matched healthy controls were selected from the trauma database. Measures of nutrition status included a scaled scoring of core muscle mass, and visceral and subcutaneous fat stores. Analysis was conducted using the pooled and individually matched subject-control differences. There were 81 subjects included in the final analysis (liver (n = 35), kidney (n = 20) and intestine (n = 26)). Children with end-stage liver disease had a 23% reduction in muscle mass, a 69% increase in visceral fat and a 29% increase in subcutaneous fat. End-stage renal disease patients had a 19% reduction in muscle mass and a 258% increase in subcutaneous fat. Intestine failure patients had a 24% reduction in muscle mass, a 30% increase in visceral fat and a 46% increase in subcutaneous fat. These results demonstrate significant sarcopenia and increased fat stores in end-stage organ failure patients which supports the idea of an active physiologic mechanism to store fat while losing muscle mass. Sarcopenia may be related to total protein loss from a catabolic state, or from decreased synthesis (liver), wasting (kidney) or malabsorption (intestine).

  14. Increased incidence of head and neck cancer in liver transplant recipients: a meta-analysis.

    PubMed

    Liu, Qian; Yan, Lifeng; Xu, Cheng; Gu, Aihua; Zhao, Peng; Jiang, Zhao-Yan

    2014-10-22

    It is unclear whether liver transplantation is associated with an increased incidence of post-transplant head and neck cancer. This comprehensive meta-analysis evaluated the association between liver transplantation and the risk of head and neck cancer using data from all available studies. PubMed and Web of Science were systematically searched to identify all relevant publications up to March 2014. Standardized incidence ratio (SIR) and 95% confidence intervals (CIs) for risk of head and neck cancer in liver transplant recipients were calculated. Tests for heterogeneity, sensitivity, and publishing bias were also performed. Of the 964 identified articles, 10 were deemed eligible. These studies included data on 56,507 patients with a total follow-up of 129,448.9 patient-years. SIR for head and neck cancer was 3.836-fold higher (95% CI 2.754-4.918, P = 0.000) in liver transplant recipients than in the general population. No heterogeneity or publication bias was observed. Sensitivity analysis indicated that omission of any of the studies resulted in an SIR for head and neck cancer between 3.488 (95% CI: 2.379-4.598) and 4.306 (95% CI: 3.020-5.592). Liver transplant recipients are at higher risk of developing head and neck cancer than the general population.

  15. Increased iron deposition in rat liver fibrosis induced by a high-dose injection of dimethylnitrosamine.

    PubMed

    Guo, Limei; Enzan, Hideaki; Hayashi, Yoshihiro; Miyazaki, Eriko; Jin, Yulan; Toi, Makoto; Kuroda, Naoto; Hiroi, Makoto

    2006-12-01

    Using a developed rat model of hepatic necrosis and subsequent fibrosis induced by a high-dose intraperitoneal injection of dimethylnitrosamine (DMN), we studied iron deposition and expression of transforming growth factor-beta(1) (TGF-beta(1)) during the development of persistent liver fibrosis. Rats were sacrificed at several timepoints from 6 h to 10 months post-injection and the livers were examined for iron content and distribution, and for expression of alpha-smooth muscle actin, ED-1, TGF-beta(1), and collagen (alpha(2))I. Morphologic evidence of acute submassive hemorrhagic necrosis peaked at 36 h; on day 3 the residual parenchyma contained activated hepatic stellate cells (HSCs) and necrotic areas contained numerous macrophages; and on day 5, necrotic tissues and erythrocytes had been phagocytosed and macrophages contained abundant iron deposits. From days 7 to 10, iron-laden macrophages and activated HSCs (myofibroblasts) populated the fibrous septa in parallel. From week 2 to month 10, closely arranged macrophages and myofibroblasts were found in central-to-central bridging fibrotic tissue. TGF-beta(1) was strongly detected in both macrophages and HSCs during development of liver fibrosis. Our data suggest that increased iron deposition may be involved in the initiation and perpetuation of rat liver fibrosis. Iron-laden macrophages may influence HSCs through the action of TGF-beta(1) in DMN-induced liver fibrosis.

  16. Increase in natural killer cell activity following living-related liver transplantation.

    PubMed

    Hirata, M; Kita, Y; Saito, S; Nishimura, M; Ito, M; Mizuta, K; Tanaka, H; Harihara, Y; Kawarasaki, H; Hashizume, K; Makuuchi, M

    1998-01-01

    We monitored the serial changes of natural killer cell (NK) activity in eight recipients of living-related liver transplantation. The HLA types of all eight patients were haplotypically identical with those of their donors. Tacrolimus and methylprednisolone were used for immunosuppression. The NK activity before transplantation was 24.1 +/- 20.2% which is surprisingly low when compared with the value for normal individuals (67.7 +/- 13.2%, P < 0.01) or a liver dysfunction group (49.4 +/- 21.9%, P < 0.05). Serial changes in NK activity revealed a minimum of 6.1 +/- 3.6% 1 week after transplantation, gradually increasing to 49.2 +/- 12.5% at 2 months after transplantation. These results suggest that the diseased liver might play an important role in the suppression of NK activity.

  17. Increased Expression of Hepatocyte Nuclear Factor 6 Stimulates Hepatocyte Proliferation during Mouse Liver Regeneration

    PubMed Central

    Tan, Yongjun; Yoshida, Yuichi; Hughes, Douglas E.; Costa, Robert H.

    2005-01-01

    Background & Aims The Hepatocyte Nuclear Factor 6 (HNF6 or ONECUT-1) protein is a cell-type specific transcription factor that regulates expression of hepatocyte-specific genes. Using hepatocytes for Chromatin Immunoprecipitation (ChIP) assays, the HNF6 protein was shown to associate with cell cycle regulatory promoters. Here, we examined whether increased levels of HNF6 stimulate hepatocyte proliferation during mouse liver regeneration. Methods Tail vein injection of adenovirus expressing the HNF6 cDNA (AdHNF6) was used to increase hepatic HNF6 levels during mouse liver regeneration induced by partial hepatectomy, and DNA replication was determined by Bromodeoxyuridine incorporation. Cotransfection and ChIP assays were used to determine transcriptional target promoters. Results Elevated expression of HNF6 during mouse liver regeneration causes a significant increase in the number of hepatocytes entering DNA replication (S-phase) and mouse hepatoma Hepa1-6 cells diminished for HNF6 levels by siRNA transfection exhibit a 50% reduction in S-phase following serum stimulation. This stimulation in hepatocyte S-phase progression was associated with increased expression of the hepatocyte mitogen Tumor Growth Factor α (TGFα) and the cell cycle regulators Cyclin D1 and Forkhead Box m1 (Foxm1) transcription factor. Cotransfection and ChIP assays show that TGFα, Cyclin D1, and HNF6 promoter regions are direct transcriptional targets of the HNF6 protein. Co-immunoprecipitation assays with regenerating mouse liver extracts reveal association between HNF6 and Foxm1 proteins and cotransfection assays show that HNF6 stimulates Foxm1 transcriptional activity. Conclusion These mouse liver regeneration studies show that increased HNF6 levels stimulate hepatocyte proliferation through transcriptional induction of cell cycle regulatory genes. PMID:16618419

  18. Hepatic Reticuloendothelial System Cell Iron Deposition is Associated with Increased Apoptosis in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Maliken, Bryan D.; Nelson, James E.; Klintworth, Heather M.; Beauchamp, Mary; Yeh, Matthew M.; Kowdley, Kris V.

    2013-01-01

    The goal of this study was to examine the relationship between presence of hepatic iron deposition, apoptosis, histologic features and serum markers of oxidative stress and cell death in nonalcoholic fatty liver disease. Clinical, biochemical, metabolic and independent histopathologic assessment was conducted in 83 unselected patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD)from a single center. Apoptosis and necrosis in serum was quantified using serum cytokeratin-18(CK18) M30 and M65ELISAsand in liver by TUNEL stainingin situ. Serum malondialdehyde(MDA) and thioredoxin-1 (Trx-1) levels were measured to evaluate oxidative stress. Presence of reticuloendothelial system cell (RES) iron in the liver was associated with nonalcoholic steatohepatitis (p<0.05) and increased hepatic TUNEL staining (p=0.02),as well as increased serum levels of apoptosis-specific (M30, p=0.013) and total (M65, p=0.006) CK-18 fragments, higher MDA (p=0.002) and lower antioxidant Trx-1 levels (p=0.012) compared to patients without stainable hepatic iron. NAFLD patients with a hepatocellular iron staining pattern also had increased serum MDA (p=0.006) but not M30 CK-18 levels or TUNEL staining compared to subjects without stainable hepatic iron. Patients with iron deposition limited to hepatocytes had a lower proportion of apoptosis-specific M30 fragments relative to total M65 CK-18 levels (37% vs. ≤ 25%, p<0.05). Conclusions Presence of iron in liver RES cells is associated with NASH, increased apoptosis and increased oxidative stress. Hepatocellular iron deposition in NAFLD is also associated with oxidative stress and may promote hepatocyte necrosis in this disease. PMID:23325576

  19. Hepatic reticuloendothelial system cell iron deposition is associated with increased apoptosis in nonalcoholic fatty liver disease.

    PubMed

    Maliken, Bryan D; Nelson, James E; Klintworth, Heather M; Beauchamp, Mary; Yeh, Matthew M; Kowdley, Kris V

    2013-05-01

    The aim of this study was to examine the relationship between the presence of hepatic iron deposition, apoptosis, histologic features, and serum markers of oxidative stress (OS) and cell death in nonalcoholic fatty liver disease (NAFLD). Clinical, biochemical, metabolic, and independent histopathologic assessment was conducted in 83 unselected patients with biopsy-proven NAFLD from a single center. Apoptosis and necrosis in serum was quantified using serum cytokeratin 18 (CK18) M30 and M65 enzyme-linked immunosorbent assays and in liver by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in situ. Serum malondialdehyde (MDA) and thioredoxin-1 (Trx1) levels were measured to evaluate OS. Presence of reticuloendothelial system (RES) cell iron in the liver was associated with nonalcoholic steatohepatitis (P < 0.05) and increased hepatic TUNEL staining (P = 0.02), as well as increased serum levels of apoptosis-specific (M30; P = 0.013) and total (M65; P = 0.006) CK18 fragments, higher MDA (P = 0.002) and lower antioxidant Trx1 levels (P = 0.012), compared to patients without stainable hepatic iron. NAFLD patients with a hepatocellular (HC) iron staining pattern also had increased serum MDA (P = 0.006), but not M30 CK18 levels or TUNEL staining, compared to subjects without stainable hepatic iron. Patients with iron deposition limited to hepatocytes had a lower proportion of apoptosis-specific M30 fragments relative to total M65 CK18 levels (37% versus ≤25%; P < 0.05). Presence of iron in liver RES cells is associated with NASH, increased apoptosis, and increased OS. HC iron deposition in NAFLD is also associated with OS and may promote hepatocyte necrosis in this disease. Copyright © 2013 American Association for the Study of Liver Diseases.

  20. Attenuation of epinephrine-induced increase in liver cyclic AMP by endogeneous insulin in vivo.

    PubMed

    Shikama, H; Ui, M

    1976-09-24

    1. Epinephrine-induced increase in rat liver cyclic AMP in vivo was potentiated when the circulating insulin was suppressed by injection of anti-insulin serum or by induction of diabetes. Consequently, phosphorylase was activated, glycogen synthetase was inactivated and glycogen accumulation induced by glucose load was prevented by epinephrine in the insulin-deficient rats to a much larger extent than in normal rats. 2. Insulin lack was effective in potentiating epinephrine-induced increase in liver and muscule cyclic AMP even after the treatment of rats with theophylline; the potentiation could not be solely accounted for by the inhibition of cyclic AMP phosphodiesterase. Thus, it is likely that insulin lack enhaces epinephrine activation of adenylate cyclase. 3. Unlike epinephrine, glucagon increased liver cyclic AMP to essentially the same extent whether the rat was treated with anti-insulin serum or not. 4. Based on the difference in dose-response curves between normal and insulin-deficient rats, a possibility is discussed that there are two adenylate cylase in the liver with higher and lower affinities for epinephrine and that circulating insulin blocks the high affinity enzyme selectively.

  1. Antibiotic Exposure in Early Life Increases Risk of Childhood Obesity: A Systematic Review and Meta-Analysis.

    PubMed

    Shao, Xiaoqing; Ding, Xiaolian; Wang, Bin; Li, Ling; An, Xiaofei; Yao, Qiuming; Song, Ronghua; Zhang, Jin-An

    2017-01-01

    A number of studies have previously assessed the impact of antibiotic exposure in early life on the risk of childhood obesity, but no systematic assessment is currently available. A systematic review and meta-analysis was performed to comprehensively and quantitatively elucidate the risk of childhood obesity caused by antibiotic exposure in early life. Literature search was performed in PubMed, Embase, and Web of Science. Random-effect meta-analysis was used to pool the statistical estimates. Fifteen cohort studies involving 445,880 participants were finally included, and all those studies were performed in developed countries. Antibiotic exposure in early life significantly increased risk of childhood overweight [relative risk (RR) = 1.23, 95% confidence interval (CI) 1.13-1.35, P < 0.001] and childhood obesity (RR = 1.21, 95% CI 1.13-1.30, P < 0.001). Antibiotic exposure in early life also significantly increased the z-score of childhood body mass index (mean difference: 0.07, 95% CI 0.05-0.09, P < 0.00001). Importantly, there was an obvious dose-response relationship between antibiotic exposure in early life and childhood adiposity, with a 7% increment in the risk of overweight (RR = 1.07, 95% CI 1.01-1.15, P = 0.03) and a 6% increment in the risk of obesity (RR = 1.06, 95% CI 1.02-1.09, P < 0.001) for each additional course of antibiotic exposure. In conclusion, antibiotic exposure in early life significantly increases risk of childhood obesity. Moreover, current analyses are mainly taken from developed countries, and therefore the impact of antibiotic exposure on risk of childhood obesity in vulnerable populations or developing countries still needs to be evaluated in future studies.

  2. Birth size and accelerated growth during infancy are associated with increased odds of childhood overweight in Mexican children.

    PubMed

    Jones-Smith, Jessica C; Fernald, Lia C H; Neufeld, Lynnette M

    2007-12-01

    The associations of birth size, rate of growth during infancy, and odds of childhood overweight have not yet been thoroughly investigated in contemporary cohorts in low- and middle-income countries. The primary aim of this study was to evaluate the influence of birth size (using body mass index at birth) and accelerated growth during infancy (defined as upward growth curve percentile crossing between birth and age 1 year) on the odds of childhood overweight. A secondary goal was to characterize the sociodemographic correlates of accelerated growth during infancy. Observational prospective cohort. Participants were 163 children and their mothers living in semiurban Mexico who were originally recruited between 1997 and 2000 and followed until 2005. Primary outcome was childhood overweight (as assessed by body mass index). Secondary outcome was accelerated growth during infancy. Multivariate linear regression and logistic regression were used to determine the associations among birth size, accelerated growth, and childhood overweight. Increased size at birth and accelerated growth during the first year of life increased the odds of childhood overweight (odds ratio [OR] 7.62, P<0.0005 and OR 2.23, P<0.05, respectively). The effect of accelerated growth on odds of childhood overweight varied by size at birth (OR for interaction term 0.63, P<0.05). Living in a "dual burden" household, where the child was underweight at birth and the mother was overweight 4 to 6 years after birth, was associated with accelerated growth during the first year of life. In a sample of Mexican children living in poverty, accelerated growth during infancy was associated with increased odds of childhood overweight among small and normal-sized babies. Among large babies, accelerated growth did not appear to pose an additional risk for overweight beyond that of high birth weight. Upward growth curve percentile crossing in infancy may be predictive of future childhood overweight status

  3. Atherogenic diet increases cholesteryl ester transfer protein messenger RNA levels in rabbit liver.

    PubMed

    Quinet, E M; Agellon, L B; Kroon, P A; Marcel, Y L; Lee, Y C; Whitlock, M E; Tall, A R

    1990-02-01

    Cholesteryl ester transfer activity is increased in plasma of cholesterol-fed rabbits. To investigate the mechanisms leading to changes in activity, we measured cholesteryl ester transfer protein (CETP) mass by RIA and CETP mRNA abundance by Northern and slot blot analysis using a human CETP cDNA probe in control (n = 8) and cholesterol-fed rabbits (n = 10). Cholesterol feeding (chow plus 0.5% cholesterol, 10% corn oil) for 30 d increased CETP mass in plasma 3.2-fold in the cholesterol-fed rabbits (12.45 +/- 0.82 micrograms/ml) compared with controls (3.86 +/- 0.38 micrograms/ml). In the hypercholesterolemic rabbit, liver CETP mRNA levels were increased 2.8 times control mRNA levels. Actin, apo E, lecithin-cholesterol acyltransferase, and albumin mRNA abundances were unchanged. In contrast to the widespread tissue distribution in humans, CETP mRNA was not detected in extrahepatic tissues of either control or cholesterol-fed animals. Using a sensitive RNase protection assay, the increase in liver CETP mRNA was detectable within 3 d of beginning the high cholesterol diet. Thus, in response to the atherogenic diet there is an early increase in liver CETP mRNA, probably causing increased CETP synthesis and secretion, and increased plasma CETP. The results indicate that the CETP gene may be regulated by diet-induced changes in lipid metabolism.

  4. Increased incidence of childhood leukemia in urban areas: a population-based case-control study.

    PubMed

    Malagoli, Carlotta; Malavolti, Marcella; Costanzini, Sofia; Fabbri, Sara; Tezzi, Sergio; Palazzi, Giovanni; Arcolin, Elisa; Vinceti, Marco

    2015-01-01

    We carried out a population-based case-control study to assess the possibility of an excess risk of childhood leukemia in urban areas, independently from road traffic pollution. Study subjects were the 111 cases of childhood leukemia diagnosed from 1998 to 2011 among residents of two provinces of the northern Italian Emilia-Romagna region, and 444 controls matched by age and sex. Through mapping of the region carried out by remote sensing, we examined the percentage of urban or rural area in the 100-meter circular buffer around each child's house. We also modeled annual average exposure to benzene and PM10 from vehicular traffic at each residence. In a multivariate model adjusting for benzene and PM10, the odds ratio of leukemia associated with residence in a highly urbanized area and residential area (≥95% land use of this type near the child's home) was 1.4 (95% confidence intervals 0.8-2.4) and 1.3 (0.8-2.2), respectively. An increased risk was also found in association with the proximity to «dumps, scrap yards, and building sites». No association emerged with residence in rural areas or near industrial plants. These results indicate that children living in urban areas experience an excess leukemia risk, independently from exposure to pollutants from vehicles.

  5. O-GlcNAcylation Increases ChREBP Protein Content and Transcriptional Activity in the Liver

    PubMed Central

    Guinez, Céline; Filhoulaud, Gaëlle; Rayah-Benhamed, Fadila; Marmier, Solenne; Dubuquoy, Céline; Dentin, Renaud; Moldes, Marthe; Burnol, Anne-Françoise; Yang, Xiaoyong; Lefebvre, Tony; Girard, Jean; Postic, Catherine

    2011-01-01

    OBJECTIVE Carbohydrate-responsive element–binding protein (ChREBP) is a key transcription factor that mediates the effects of glucose on glycolytic and lipogenic genes in the liver. We have previously reported that liver-specific inhibition of ChREBP prevents hepatic steatosis in ob/ob mice by specifically decreasing lipogenic rates in vivo. To better understand the regulation of ChREBP activity in the liver, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAc or O-GlcNAcylation), an important glucose-dependent posttranslational modification playing multiple roles in transcription, protein stabilization, nuclear localization, and signal transduction. RESEARCH DESIGN AND METHODS O-GlcNAcylation is highly dynamic through the action of two enzymes: the O-GlcNAc transferase (OGT), which transfers the monosaccharide to serine/threonine residues on a target protein, and the O-GlcNAcase (OGA), which hydrolyses the sugar. To modulate ChREBPOG in vitro and in vivo, the OGT and OGA enzymes were overexpressed or inhibited via adenoviral approaches in mouse hepatocytes and in the liver of C57BL/6J or obese db/db mice. RESULTS Our study shows that ChREBP interacts with OGT and is subjected to O-GlcNAcylation in liver cells. O-GlcNAcylation stabilizes the ChREBP protein and increases its transcriptional activity toward its target glycolytic (L-PK) and lipogenic genes (ACC, FAS, and SCD1) when combined with an active glucose flux in vivo. Indeed, OGT overexpression significantly increased ChREBPOG in liver nuclear extracts from fed C57BL/6J mice, leading in turn to enhanced lipogenic gene expression and to excessive hepatic triglyceride deposition. In the livers of hyperglycemic obese db/db mice, ChREBPOG levels were elevated compared with controls. Interestingly, reducing ChREBPOG levels via OGA overexpression decreased lipogenic protein content (ACC, FAS), prevented hepatic steatosis, and improved the lipidic profile of OGA-treated db/db mice

  6. Increased hepcidin in transferrin-treated thalassemic mice correlates with increased liver BMP2 expression and decreased hepatocyte ERK activation.

    PubMed

    Chen, Huiyong; Choesang, Tenzin; Li, Huihui; Sun, Shuming; Pham, Petra; Bao, Weili; Feola, Maria; Westerman, Mark; Li, Guiyuan; Follenzi, Antonia; Blanc, Lionel; Rivella, Stefano; Fleming, Robert E; Ginzburg, Yelena Z

    2016-03-01

    Iron overload results in significant morbidity and mortality in β-thalassemic patients. Insufficient hepcidin is implicated in parenchymal iron overload in β-thalassemia and approaches to increase hepcidin have therapeutic potential. We have previously shown that exogenous apo-transferrin markedly ameliorates ineffective erythropoiesis and increases hepcidin expression in Hbb(th1/th1) (thalassemic) mice. We utilize in vivo and in vitro systems to investigate effects of exogenous apo-transferrin on Smad and ERK1/2 signaling, pathways that participate in hepcidin regulation. Our results demonstrate that apo-transferrin increases hepcidin expression in vivo despite decreased circulating and parenchymal iron concentrations and unchanged liver Bmp6 mRNA expression in thalassemic mice. Hepatocytes from apo-transferrin-treated mice demonstrate decreased ERK1/2 pathway and increased serum BMP2 concentration and hepatocyte BMP2 expression. Furthermore, hepatocyte ERK1/2 phosphorylation is enhanced by neutralizing anti-BMP2/4 antibodies and suppressed in vitro in a dose-dependent manner by BMP2, resulting in converse effects on hepcidin expression, and hepatocytes treated with MEK/ERK1/2 inhibitor U0126 in combination with BMP2 exhibit an additive increase in hepcidin expression. Lastly, bone marrow erythroferrone expression is normalized in apo-transferrin treated thalassemic mice but increased in apo-transferrin injected wild-type mice. These findings suggest that increased hepcidin expression after exogenous apo-transferrin is in part independent of erythroferrone and support a model in which apo-transferrin treatment in thalassemic mice increases BMP2 expression in the liver and other organs, decreases hepatocellular ERK1/2 activation, and increases nuclear Smad to increase hepcidin expression in hepatocytes.

  7. Platelet count increase following phlebotomy in iron overloaded patients with liver cirrhosis.

    PubMed

    Franchini, Massimo

    2003-08-01

    Thrombocytopenia is a frequent hematological complication in patients with liver cirrhosis, but its pathogenesis is not clearly understood. We evaluated the effect of iron depletion by phlebotomy on platelet count in 62 consecutive iron overloaded patients with liver cirrhosis and thrombocytopenia. After a median follow-up of 30.2 months we observed a significant increase of platelet count in all patients (from mean baseline levels of 110.1 up to 168.22109/l at the end of follow-up, P<0.001) with platelet count normalization in 42 of them (67.7%). In addition, we observed a significant improvement of serum ALT levels (from pretreatment mean values of 126.7 up to 59.7 U/l at the end of follow-up, P<0.001) along with the reduction of serum ferritin levels and transferrin saturation during phlebotomy. Different pathogenetic mechanisms involving both humoral (erythropoietin and thrombopoietin, TPO) and physical (portal hypertension and hypersplenism) factors are here discussed to explain the platelet count increase following phlebotomy. Our results show that phlebotomy is effective not only in lowering iron overload, but also in improving liver function and thrombocytopenia in patients with liver cirrhosis.

  8. Polμ Deficiency Increases Resistance to Oxidative Damage and Delays Liver Aging

    PubMed Central

    Escudero, Beatriz; Lucas, Daniel; Albo, Carmen; Dhup, Suveera; Bacher, Jeff W.; Sánchez-Muñoz, Aránzazu; Fernández, Margarita; Rivera-Torres, José; Carmona, Rosa M.; Fuster, Encarnación; Carreiro, Candelas; Bernad, Raquel; González, Manuel A.; Andrés, Vicente; Blanco, Luis; Roche, Enrique; Fabregat, Isabel; Samper, Enrique; Bernad, Antonio

    2014-01-01

    Polμ is an error-prone PolX polymerase that contributes to classical NHEJ DNA repair. Mice lacking Polμ (Polμ−/−) show altered hematopoiesis homeostasis and DSB repair and a more pronounced nucleolytic resection of some V(D)J junctions. We previously showed that Polμ−/− mice have increased learning capacity at old ages, suggesting delayed brain aging. Here we investigated the effect of Polμ−/− deficiency on liver aging. We found that old Polμ−/− mice (>20 month) have greater liver regenerative capacity compared with wt animals. Old Polμ−/− liver showed reduced genomic instability and increased apoptosis resistance. However, Polμ−/− mice did not show an extended life span and other organs (e.g., heart) aged normally. Our results suggest that Polμ deficiency activates transcriptional networks that reduce constitutive apoptosis, leading to enhanced liver repair at old age. PMID:24691161

  9. Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats.

    PubMed

    Froh, Matthias; Conzelmann, Lars; Walbrun, Peter; Netter, Susanne; Wiest, Reiner; Wheeler, Michael-D; Lehnert, Mark; Uesugi, Takehiko; Scholmerich, Jurgen; Thurman, Ronald G

    2007-07-07

    To investigate the effects of heme oxygenase-1 (HO-1) against oxidant-induced injury caused by bile duct ligation (BDL). Either cobalt protoporphyrin (CoPP), a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis. Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and cytokine and collagen-Ialpha (Col-Ialpha) mRNA expression was detected using RNase protection assays. Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly, enzyme release was not reduced in rats receiving CoPP. Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius red-positive areas were increased to about 11.7% after BDL. Collagen-Ialpha and TGF-beta mRNA increased significantly by BDL. Again, this effect was increased by HO-1 overexpression. Hepatic fibrosis due to BDL is not reduced by the HO-1 inducer CoPP. In contrast, HO-1 overexpression increases liver injury in rats under conditions of experimental chronic cholestasis.

  10. Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

    PubMed Central

    Froh, Matthias; Conzelmann, Lars; Walbrun, Peter; Netter, Susanne; Wiest, Reiner; Wheeler, Michael D; Lehnert, Mark; Uesugi, Takehiko; Scholmerich, Jurgen; Thurman, Ronald G

    2007-01-01

    AIM: To investigate the effects of heme oxygenase-1 (HO-1) against oxidant-induced injury caused by bile duct ligation (BDL). METHODS: Either cobalt protoporphyrin (CoPP), a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis. Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and cytokine and collagen-Iα (Col-Iα) mRNA expression was detected using RNase protection assays. RESULTS: Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly, enzyme release was not reduced in rats receiving CoPP. Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius red-positive areas were increased to about 11.7% after BDL. Collagen-Iα and TGF-β mRNA increased significantly by BDL. Again, this effect was increased by HO-1 overexpression. CONCLUSION: Hepatic fibrosis due to BDL is not reduced by the HO-1 inducer CoPP. In contrast, HO-1 overexpression increases liver injury in rats under conditions of experimental chronic cholestasis. PMID:17659695

  11. Catalase increases ethanol oxidation through the purine catabolism in rat liver.

    PubMed

    Villalobos-García, Daniel; Hernández-Muñoz, Rolando

    2017-08-01

    Hepatic ethanol oxidation increases according to its concentration and is raised to near-saturation levels of alcohol dehydrogenase (ADH); therefore, re-oxidation of NADH becomes rate limiting in ethanol metabolism by the liver. Adenosine is able to increase liver ethanol oxidation in both in vivo and in vitro conditions; the enhancement being related with the capacity of the nucleoside to accelerate the transport of cytoplasmic reducing equivalents to mitochondria, by modifying the subcellular distribution of the malate-aspartate shuttle components. In the present study, we explored the putative effects of adenosine and other purines on liver ethanol oxidation mediated by non-ADH pathways. Using the model of high precision-cut rat liver slices, a pronounced increase of ethanol oxidation was found in liver slices incubated with various intermediates of the purine degradation pathway, from adenosine to uric acid (175-230%, over controls). Of these, urate had the strongest (230%), whereas xanthine had the less pronounced effect (178% over controls). The enhancement was not abolished by 4-methylpyrazole, indicating that the effect was independent of alcohol dehydrogenase. Conversely, aminotriazole, a catalase inhibitor, completely abolished the effect, pointing out that this enhanced ethanol oxidation is mediated by catalase activity. It is concluded that the H2O2 needed for catalase activity is derived from the oxidation of (hypo)xanthine by xanthine oxidase and the oxidation of urate by uricase. The present and previous data led us to propose that, depending on the metabolic conditions, adenosine might be able to stimulate the metabolism of ethanol through different pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Several statins increase body and liver fat accumulation in a model of metabolic syndrome.

    PubMed

    Aguirre, L; Hijona, E; Macarulla, M T; Gracia, A; Larrechi, I; Bujanda, L; Hijona, L; Portillo, M P

    2013-06-01

    Statins are a family of drugs used in hypercholesterolemia. The aim of this study was to analyze the effect of statins on body and liver fat accumulation in obese Zucker rats. Seventy Zucker (fa/fa) rats were divided into seven groups. Rats from six statin groups were treated with pravastatin, simvastatin, atorvastatin, rosuvastatin, fluvastatin and lovastatin respectively, at a dose of 0.6 mg/kg body weight/day. After 6 weeks, liver and white adipose tissue from intra-abdominal and subcutaneous locations were dissected and weighed. Subcutaneous adipose tissue from rosuvastatin, atorvastatin, fluvastatin and lovastatin treated rats was significantly increased. Fatty acid synthase (FAS) activity was increased by the administration of fluvastatin and lovastatin, as was glucose-6-P dehydrogenase (G6PDH) by the administration of atorvastatin and lovastatin. No changes were observed in malic enzyme (ME) activity. Furthermore, heparin-releasable lipoprotein lipase (HR-LPL) was increased in all groups where the subcutaneous depot was increased, and total LPL increased only in rosuvastatin and fluvastatin-treated groups. With regard to liver, there were no changes in weight but the amount of triacylglycerols was increased in rosuvastatin group, as well as its liver damage was higher. In this group FAS and G6PDH activities were increased and no changes were observed in ME, acyl CoA oxidase (ACO) and carnitine palmitoyltransferase-1a (CPT-1a) activities. All statins, with the exception of simvastatin, worsen insulin resistance. These results show that statins have different effects on body fat accumulation. Moreover, rosuvastatin also shows a prosteatotic effect. These results should be taken into account for statin choice in prescription.

  13. Maintenance of Increased Childhood Influenza Vaccination Rates 1 Year After an Intervention in Primary Care Practices.

    PubMed

    Nowalk, Mary Patricia; Zimmerman, Richard K; Lin, Chyongchiou Jeng; Reis, Evelyn Cohen; Huang, Hsin-Hui; Moehling, Krissy K; Hannibal, Kristin M; Matambanadzo, Annamore; Shenouda, Emeil M; Allred, Norma J

    2016-01-01

    Influenza vaccination rates among some groups of children remain below the Healthy People 2020 goal of 70%. Multistrategy interventions to increase childhood influenza vaccination have not been evaluated recently. Twenty pediatric and family medicine practices were randomly assigned to receive the intervention in either year 1 or year 2. This study focuses on influenza vaccine uptake in the 10 year 1 intervention sites during intervention and the following maintenance year. The intervention included the 4 Pillars Immunization Toolkit-a practice improvement toolkit, early delivery of donated vaccine for disadvantaged children, staff education, and feedback on progress. During the maintenance year, practices were not assisted or contacted, except to complete follow-up surveys. Student's t tests assessed vaccine uptake of children aged 6 months to 18 years, and multilevel regression modeling in repeated measures determined variables related to the likelihood of vaccination. Influenza vaccine uptake increased 12.4 percentage points (PP; P < .01) during active intervention and uptake was sustained (+0.4 PP; P > .05) during maintenance, for an average change of 12.7 PP over all sites, increasing from 42.2% at baseline to 54.9% (P < .001) during maintenance. In regression modeling that controlled for age, race, and insurance, likelihood of vaccination was greater during intervention than baseline (odds ratio 1.47; 95% confidence interval 1.44-1.50; P < .001) and greater during maintenance than baseline (odds ratio 1.50; 95% confidence interval 1.47-1.54; P < .001). In primary care practices, a multistrategy intervention that included the 4 Pillars Immunization Toolkit, early delivery of vaccine, and feedback was associated with significant improvements in childhood influenza vaccination rates that were maintained 1 year after active intervention. Copyright © 2016 Academic Pediatric Association. All rights reserved.

  14. Hyperammonemia Is Associated with Increasing Severity of Both Liver Cirrhosis and Hepatic Encephalopathy

    PubMed Central

    Ayub, Maimoona; Khan, Wazir Mohammad

    2016-01-01

    Background. Hyperammonemia resulting from chronic liver disease (CLD) can potentially challenge and damage any organ system of the body, particularly the brain. However, there is still some controversy regarding the diagnostic or prognostic values of serum ammonia in patients with over hepatic encephalopathy, especially in the setting of acute-on-chronic or chronic liver failure. Moreover, the association of serum ammonia with worsening Child-Pugh grade of liver cirrhosis has not been studied. Objective. This study was conducted to solve the controversy regarding the association between hyperammonemia and cirrhosis, especially hepatic encephalopathy in chronically failed liver. Material and Methods. In this study, 171 cirrhotic patients had their serum ammonia measured and analyzed by SPSS version 16. Chi-squared test and one-way ANOVA were applied. Results. The study had 110 male and 61 female participants. The mean age of all the participants in years was 42.33 ± 7.60. The mean duration (years) of CLD was 10.15 ± 3.53 while the mean Child-Pugh (CP) score was 8.84 ± 3.30. Chronic viral hepatitis alone was responsible for 71.3% of the cases. Moreover, 86.5% of participants had hepatic encephalopathy (HE). The frequency of hyperammonemia was 67.3%, more frequent in males (N = 81, z-score = 2.4, and P < 0.05) than in females (N = 34, z-score = 2.4, and P < 0.05), and had a statistically significant relationship with increasing CP grade of cirrhosis (χ2(2) = 27.46, P < 0.001, Phi = 0.40, and P < 0.001). Furthermore, serum ammonia level was higher in patients with hepatic encephalopathy than in those without it; P < 0.001. Conclusion. Hyperammonemia is associated with both increasing Child-Pugh grade of liver cirrhosis and hepatic encephalopathy. PMID:27847646

  15. Transient Elastography-Based Liver Stiffness Age-Dependently Increases in Children

    PubMed Central

    Tokuhara, Daisuke; Cho, Yuki; Shintaku, Haruo

    2016-01-01

    Background and Aims Pediatric use of liver transient elastography (TE) is attractive for its non-invasiveness, but reference values have not been established. We aimed to determine reference values for TE in children. Methods In pediatric patients (1 to 18 years), TE (FibroScan®) with an M probe was used for both liver stiffness measurement (LSM) and measurement of hepatic fat deposition by using a controlled attenuation parameter (CAP). The patients were divided into three relevant age groups: preschoolers (1 to 5 years), elementary school children (6 to 11 years), and adolescents (12 to 18 years). Overweight or obese patients or those with known liver disease, elevated serum liver enzymes, or hepatic echogenic abnormality were excluded from the study. Results Among 139 children, 123 (88.5%; 62 male; median age, 11.7 years; age range, 1.3 to 17.2 years) were successfully subjected to M-probe TE without anesthesia. Median LSM increased with age: it was 3.4 kPa (2.3 to 4.6 kPa, 5th to 95th percentiles) at ages 1 to 5 years; 3.8 (2.5 to 6.1) kPa at ages 6 to 11; and 4.1 (3.3 to 7.9) kPa at ages 12 to 18 (P = 0.001). Median CAP was not age dependent: it was 183 (112 to 242) for ages 1 to 18 years. Conclusions M-probe TE is suitable in a wide age range of children from age 1 year up. In children without evidence of liver disease, LSM has an age-dependent increase, whereas CAP does not differ between ages 1 and 18. PMID:27861607

  16. QT prolongation is associated with increased mortality in end stage liver disease.

    PubMed

    Kim, Sun Moon; George, Bennet; Alcivar-Franco, Diego; Campbell, Charles L; Charnigo, Richard; Delisle, Brian; Hundley, Jonathan; Darrat, Yousef; Morales, Gustavo; Elayi, Samy-Claude; Bailey, Alison L

    2017-04-26

    To determine the prevalence of QT prolongation in a large series of end stage liver disease (ESLD) patients and its association to clinical variables and mortality. The QT interval was measured and corrected for heart rate for each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females. Multiple clinical variables were evaluated including sex, age, serum sodium, international normalized ratio, creatinine, total bilirubin, beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology of liver disease. Among 406 ESLD patients analyzed, 207 (51.0%) had QT prolongation. The only clinical variable associated with QT prolongation was male gender (OR = 3.04, 95%CI: 2.01-4.60, P < 0.001). During the study period, 187 patients (46.1%) died. QT prolongation was a significant independent predictor of mortality (OR = 1.69, 95%CI: 1.03-2.77, P = 0.039). In addition, mortality was also associated with viral etiology of ESLD, elevated MELD score and its components (P < 0.05 for all). No significant reversibility in the QT interval was seen after liver transplantation. QT prolongation was commonly encountered in an ESLD population, especially in males, and served as a strong independent marker for increased mortality in ESLD patients.

  17. QT prolongation is associated with increased mortality in end stage liver disease

    PubMed Central

    Kim, Sun Moon; George, Bennet; Alcivar-Franco, Diego; Campbell, Charles L; Charnigo, Richard; Delisle, Brian; Hundley, Jonathan; Darrat, Yousef; Morales, Gustavo; Elayi, Samy-Claude; Bailey, Alison L

    2017-01-01

    AIM To determine the prevalence of QT prolongation in a large series of end stage liver disease (ESLD) patients and its association to clinical variables and mortality. METHODS The QT interval was measured and corrected for heart rate for each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females. Multiple clinical variables were evaluated including sex, age, serum sodium, international normalized ratio, creatinine, total bilirubin, beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology of liver disease. RESULTS Among 406 ESLD patients analyzed, 207 (51.0%) had QT prolongation. The only clinical variable associated with QT prolongation was male gender (OR = 3.04, 95%CI: 2.01-4.60, P < 0.001). During the study period, 187 patients (46.1%) died. QT prolongation was a significant independent predictor of mortality (OR = 1.69, 95%CI: 1.03-2.77, P = 0.039). In addition, mortality was also associated with viral etiology of ESLD, elevated MELD score and its components (P < 0.05 for all). No significant reversibility in the QT interval was seen after liver transplantation. CONCLUSION QT prolongation was commonly encountered in an ESLD population, especially in males, and served as a strong independent marker for increased mortality in ESLD patients. PMID:28515853

  18. Nonalcoholic fatty liver may increase the risk of operation in patients with fatty liver and the frequency of cancer in their first-degree relatives.

    PubMed

    Basaranoglu, Metin; Canbakan, Billur; Yildiz, Kemal; Ceylan, Bahadir; Baysal, Birol; Uysal, Omer; Senturk, Hakan

    2016-10-01

    Fatty liver is a common disease in developed countries. We investigated the frequency of operation in patients with fatty liver and the frequency of cancer in their first-degree relatives. In this study, we evaluated 105 patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD), 121 patients with hepatitis C (61 patients with fatty liver and 60 patients without fatty liver), 50 patients with inflammatory bowel disease (IBD), and 109 patients with dyspepsia as a control group. There was no difference for sex, mean age, and marital status among the groups, except that patients with IBD were younger than others (p < 0.001). The frequency of cancer in family was as follows: 18 % in IBD, 9 % in dyspepsia, 28 % in hepatitis C with hepatic steatosis, 21.5 % in hepatitis C without steatosis, and 27 % in NAFLD (p = 0.006). Then, we divided the study group into two groups-group 1: IBD + dyspepsia + hepatitis C without hepatic steatosis, and group 2: hepatitis C with hepatic steatosis + NAFLD-and performed the same analysis. We found that the frequency of cancer in family was 16 % in group 1 (the patients without fatty liver) vs. 24.4 % in group 2 (those with fatty liver; p = 0.037). We also investigated the rate of operation in patients. The results were as follows: 33 % in group 1 vs. 43 % in group 2 (p = 0.043). Independently of the underlying chronic diseases, occurrence of fat in the liver increased the frequency of operation in patients with fatty liver and the rate of cancer in their first-degree relatives. Understanding the underlying causes of fatty liver forms might decrease the cancer frequency in the population and number of operation in patients with fatty liver.

  19. UDP-glucuronosyltransferase expression in mouse liver is increased in obesity- and fasting-induced steatosis.

    PubMed

    Xu, Jialin; Kulkarni, Supriya R; Li, Liya; Slitt, Angela L

    2012-02-01

    UDP-glucuronosyltransferases (Ugt) catalyze phase II conjugation reactions with glucuronic acid, which enhances chemical polarity and the elimination from the body. Few studies have addressed whether Ugt expression and activity are affected by liver disease, such as steatosis. The purpose of this study was to determine whether steatosis induced by obesity or fasting could affect liver Ugt mRNA expression and activity. Male C57BL/6J and Lep(ob/ob) (ob/ob) mice were fed ad libitum or food was withheld for 24 h. In steatotic livers of ob/ob mice, Ugt1a1, -1a6, -1a9, -2a3, -3a1, and -3a2 mRNA expression increased. Fasting, which also induced steatosis, increased hepatic Ugt1a1, -1a6, -1a7, -1a9, -2b1, -2b5, -2a3, -3a1, and -3a2 mRNA expression in mouse liver. Likewise, acetaminophen glucuronidation increased by 47% in hepatic microsomes from ob/ob mice compared with that in C57BL/6J mice, but not after fasting. In both steatosis models, Ugt induction was accompanied by increased aryl hydrocarbon receptor, constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor (PPAR)-α, pregnane X receptor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and peroxisome proliferator-activated receptor-γ coactivator-1α mRNA expression. In addition, fasting increased CAR, PPAR, and Nrf2 binding activity. The work points to hepatic triglyceride concentrations corresponding with nuclear receptor and Ugt expression. The findings indicate that steatosis significantly alters hepatic Ugt expression and activity, which could have a significant impact on determining circulating hormone levels, drug efficacy, and environmental chemical clearance.

  20. UDP-Glucuronosyltransferase Expression in Mouse Liver Is Increased in Obesity- and Fasting-Induced Steatosis

    PubMed Central

    Xu, Jialin; Kulkarni, Supriya R.; Li, Liya

    2012-01-01

    UDP-glucuronosyltransferases (Ugt) catalyze phase II conjugation reactions with glucuronic acid, which enhances chemical polarity and the elimination from the body. Few studies have addressed whether Ugt expression and activity are affected by liver disease, such as steatosis. The purpose of this study was to determine whether steatosis induced by obesity or fasting could affect liver Ugt mRNA expression and activity. Male C57BL/6J and Lepob/ob (ob/ob) mice were fed ad libitum or food was withheld for 24 h. In steatotic livers of ob/ob mice, Ugt1a1, -1a6, -1a9, -2a3, -3a1, and -3a2 mRNA expression increased. Fasting, which also induced steatosis, increased hepatic Ugt1a1, -1a6, -1a7, -1a9, -2b1, -2b5, -2a3, -3a1, and -3a2 mRNA expression in mouse liver. Likewise, acetaminophen glucuronidation increased by 47% in hepatic microsomes from ob/ob mice compared with that in C57BL/6J mice, but not after fasting. In both steatosis models, Ugt induction was accompanied by increased aryl hydrocarbon receptor, constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor (PPAR)-α, pregnane X receptor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and peroxisome proliferator-activated receptor-γ coactivator-1α mRNA expression. In addition, fasting increased CAR, PPAR, and Nrf2 binding activity. The work points to hepatic triglyceride concentrations corresponding with nuclear receptor and Ugt expression. The findings indicate that steatosis significantly alters hepatic Ugt expression and activity, which could have a significant impact on determining circulating hormone levels, drug efficacy, and environmental chemical clearance. PMID:22031624

  1. Increased liver AGEs induce hepatic injury mediated through an OST48 pathway.

    PubMed

    Zhuang, Aowen; Yap, Felicia Yt; Bruce, Clinton; Leung, Chris; Plan, Manuel R; Sullivan, Mitchell A; Herath, Chandana; McCarthy, Domenica; Sourris, Karly C; Kantharidis, Phillip; Coughlan, Melinda T; Febbraio, Mark A; Hodson, Mark P; Watt, Matthew J; Angus, Peter; Schulz, Benjamin L; Forbes, Josephine M

    2017-09-25

    The protein oligosaccharyltransferase-48 (OST48) is integral to protein N-glycosylation in the endoplasmic reticulum (ER) but is also postulated to act as a membrane localised clearance receptor for advanced glycation end-products (AGE). Hepatic ER stress and AGE accumulation are each implicated in liver injury. Hence the objective of this study was to increase the expression of OST48 and examine the effects on hepatic function and structure. Groups of 8 week old male mice (n = 10-12/group) over-expressing the gene for OST48, dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST+/-), were followed for 24 weeks, while randomised to diets either low or high in AGE content. By week 24 of the study, either increasing OST48 expression or consumption of high AGE diet impaired liver function and modestly increased hepatic fibrosis, but their combination significantly exacerbated liver injury in the absence of steatosis. DDOST+/- mice had increased both portal delivery and accumulation of hepatic AGEs leading to central adiposity, insulin secretory defects, shifted fuel usage to fatty and ketoacids, as well as hepatic glycogen accumulation causing hepatomegaly along with hepatic ER and oxidative stress. This study revealed a novel role of the OST48 and AGE axis in hepatic injury through ER stress, changes in fuel utilisation and glucose intolerance.

  2. Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Song, Byoung-Joon; Abdelmegeed, Mohamed A.; Henderson, Lauren E.; Yoo, Seong-Ho; Wan, Jie; Purohit, Vishnudutt; Hardwick, James P.; Moon, Kwan-Hoon

    2013-01-01

    Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration) under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s) of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM) as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research. PMID:23691267

  3. Novel educational interventions in residency increase knowledge of chronic liver disease and career interest in hepatology.

    PubMed

    Mikolajczyk, Adam E; Farnan, Jeanne M; McConville, John F; Jensen, Donald M; Reddy, K Gautham; Te, Helen S; Reau, Nancy; Aronsohn, Andrew I

    2016-12-01

    There is an increasing burden of chronic liver disease (CLD) in the United States but a significant shortage of hepatologists. Thus, it is necessary to develop new recruitment strategies to the field of hepatology as well as ensure that non-gastroenterology-trained physicians are able to capably assist in the care of CLD. We established a novel, nonelective, inpatient hepatology rotation that uses required modules in the American Association for the Study of Liver Diseases Curriculum and Training-First Hepatitis B and C curriculums as well as in LiverLearning. A paper-based anonymous assessment was distributed to the inaugural 25 postgraduate years 2 and 3 internal medicine residents before and after the 2-week rotation over the course of 1 year. Both the prerotation and postrotation assessments included validated multiple-choice questions and Likert-type questions, which evaluated self-perceived knowledge and comfort with managing CLD. The mean comfort level (1 = not at all comfortable/strongly disagree, 5 = very comfortable/strongly agree) of managing several common liver diseases increased significantly after completion of the rotation (i.e., cirrhosis 2.8 versus 3.8, P < 0.001; hepatitis B 2.4 versus 3.4, P = 0.001; hepatitis C 2.6 versus 3.7, P = 0.002; nonalcoholic steatohepatitis 3.0 versus 4.0, P < 0.001; liver transplant care 2.1 versus 3.4, P < 0.001). There was also a significantly increased interest in hepatology as a career (2.6 versus 3.0, P = 0.03). Finally, the mean percentage of multiple-choice questions answered correctly on the pretest was 62% and posttest was 77% (P = 0.02). Our novel curriculum and nonelective hepatology rotation has effectively demonstrated improvement in internal medicine residents' comfort with and knowledge of CLD, and increased career interest in hepatology was also observed after completion of the curriculum, which suggests that more exposure to CLD could positively impact recruitment to the workforce; larger, multicenter

  4. The heritability of general cognitive ability increases linearly from childhood to young adulthood.

    PubMed

    Haworth, C M A; Wright, M J; Luciano, M; Martin, N G; de Geus, E J C; van Beijsterveldt, C E M; Bartels, M; Posthuma, D; Boomsma, D I; Davis, O S P; Kovas, Y; Corley, R P; Defries, J C; Hewitt, J K; Olson, R K; Rhea, S-A; Wadsworth, S J; Iacono, W G; McGue, M; Thompson, L A; Hart, S A; Petrill, S A; Lubinski, D; Plomin, R

    2010-11-01

    Although common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of life, this hypothesis has not previously been tested, in part because of the large sample sizes needed for an adequately powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years) and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries, a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite life's 'slings and arrows of outrageous fortune', do genetically driven differences increasingly account for differences in general cognitive ability? We suggest that the answer lies with genotype-environment correlation: as children grow up, they increasingly select, modify and even create their own experiences in part based on their genetic propensities.

  5. Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients.

    PubMed

    Qi, Xingshun; Han, Guohong; Ye, Chun; Zhang, Yongguo; Dai, Junna; Peng, Ying; Deng, Han; Li, Jing; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Zhang, Xintong; Wang, Ran; Guo, Xiaozhong

    2016-07-19

    BACKGROUND Portal venous system thrombosis (PVST) is a life-threatening complication of liver cirrhosis. We conducted a retrospective study to comprehensively analyze the prevalence and risk factors of PVST in liver cirrhosis. MATERIAL AND METHODS All cirrhotic patients without malignancy admitted between June 2012 and December 2013 were eligible if they underwent contrast-enhanced CT or MRI scans. Independent predictors of PVST in liver cirrhosis were calculated in multivariate analyses. Subgroup analyses were performed according to the severity of PVST (any PVST, main portal vein [MPV] thrombosis >50%, and clinically significant PVST) and splenectomy. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS Overall, 113 cirrhotic patients were enrolled. The prevalence of PVST was 16.8% (19/113). Splenectomy (any PVST: OR=11.494, 95%CI=2.152-61.395; MPV thrombosis >50%: OR=29.987, 95%CI=3.247-276.949; clinically significant PVST: OR=40.415, 95%CI=3.895-419.295) and higher hemoglobin (any PVST: OR=0.974, 95%CI=0.953-0.996; MPV thrombosis >50%: OR=0.936, 95%CI=0.895-0.980; clinically significant PVST: OR=0.935, 95%CI=0.891-0.982) were the independent predictors of PVST. The prevalence of PVST was 13.3% (14/105) after excluding splenectomy. Higher hemoglobin was the only independent predictor of MPV thrombosis >50% (OR=0.952, 95%CI=0.909-0.997). No independent predictors of any PVST or clinically significant PVST were identified in multivariate analyses. Additionally, PVST patients who underwent splenectomy had a significantly higher proportion of clinically significant PVST but lower MELD score than those who did not undergo splenectomy. In all analyses, the in-hospital mortality was not significantly different between cirrhotic patient with and without PVST. CONCLUSIONS Splenectomy may increase by at least 10-fold the risk of PVST in liver cirrhosis independent of severity of liver dysfunction.

  6. Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis

    PubMed Central

    Turola, Elena; Petta, Salvatore; Vanni, Ester; Milosa, Fabiola; Valenti, Luca; Critelli, Rosina; Miele, Luca; Maccio, Livia; Calvaruso, Vincenza; Fracanzani, Anna L.; Bianchini, Marcello; Raos, Nazarena; Bugianesi, Elisabetta; Mercorella, Serena; Di Giovanni, Marisa; Craxì, Antonio; Fargion, Silvia; Grieco, Antonio; Cammà, Calogero; Cotelli, Franco; Villa, Erica

    2015-01-01

    ABSTRACT Contrasting data exist on the effect of gender and menopause on the susceptibility, development and liver damage progression in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether menopause is associated with the severity of liver fibrosis in individuals with NAFLD and to explore the issue of ovarian senescence in experimental liver steatosis in zebrafish. In 244 females and age-matched males with biopsy-proven NAFLD, we assessed anthropometric, biochemical and metabolic features, including menopausal status (self-reported); liver biopsy was scored according to ‘The Pathology Committee of the NASH Clinical Research Network’. Young and old male and female zebrafish were fed for 24 weeks with a high-calorie diet. Weekly body mass index (BMI), histopathological examination and quantitative real-time PCR analysis on genes involved in lipid metabolism, inflammation and fibrosis were performed. In the entire cohort, at multivariate logistic regression, male gender [odds ratio (OR): 1.408, 95% confidence interval (95% CI): 0.779-2.542, P=0.25] vs women at reproductive age was not associated with F2-F4 fibrosis, whereas a trend was observed for menopause (OR: 1.752, 95% CI: 0.956-3.208, P=0.06). In women, menopause (OR: 2.717, 95% CI: 1.020-7.237, P=0.04) was independently associated with F2-F4 fibrosis. Similarly, in overfed zebrafish, old female fish with failing ovarian function [as demonstrated by extremely low circulating estradiol levels (1.4±0.1 pg/µl) and prevailing presence of atretic follicles in the ovaries] developed massive steatosis and substantial fibrosis (comparable with that occurring in males), whereas young female fish developed less steatosis and were totally protected from the development of fibrosis. Ovarian senescence significantly increases the risk of fibrosis severity both in humans with NAFLD and in zebrafish with experimental steatosis. PMID:26183212

  7. Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

    PubMed Central

    Manti, Sara; Romano, Claudio; Chirico, Valeria; Filippelli, Martina; Cuppari, Caterina; Loddo, Italia; Salpietro, Carmelo; Arrigo, Teresa

    2014-01-01

    Context: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". Results: NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. Conclusions: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH. PMID:24829591

  8. Life after cancer: how does public stigma increase psychological distress of childhood cancer survivors?

    PubMed

    Kim, Min Ah; Yi, Jaehee

    2014-12-01

    Public stigma is a major source of stress for cancer survivors. However, factors that buffer or exacerbate the negative effects of public stigma on psychological distress have not been elucidated. This study examined how perceived public stigma affects psychological distress as mediated by cancer disclosure, internalized reactions to stigma, and social support availability. Cross-sectional study. The study was conducted in South Korea. The study sample was 223 adolescent and young adult survivors of childhood cancer diagnosed before the age of 19 and currently between 15 and 39 years old. Psychological distress was assessed using the Brief Symptom Inventory-18. Structural equation modeling was used with 1000 bootstrap samples. The goodness of model fit was acceptable. Public stigma perceived by cancer survivors influenced psychological distress via cancer disclosure, internalized shame, and social support availability. Higher levels of perceived public stigma predicted higher levels of internalized shame and self-blame and lower levels of social support availability, which subsequently increased psychological distress. Higher levels of perceived public stigma predicted lower levels of disclosure about cancer history and experiences. Cancer disclosure indirectly ameliorated psychological distress by reducing internalized shame. This study offers evidence that cognitive and social factors play important roles in mediating the effects of perceived public stigma on psychological distress in Korean cancer survivors. A greater understanding of factors that influence psychological distress may help psychosocial oncology service providers to identify childhood cancer survivors in need of psychosocial services and provide them with appropriate resources and interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Increasing the demand for childhood vaccination in developing countries: a systematic review.

    PubMed

    Shea, Beverley; Andersson, Neil; Henry, David

    2009-10-14

    Attempts to maintain or increase vaccination coverage almost all focus on supply side interventions: improving availability and delivery of vaccines. The effectiveness and cost-effectiveness of efforts to increase demand is uncertain. We performed a systematic review of studies that provided quantitative estimates of the impact of demand side interventions on uptake of routine childhood vaccination. We retrieved studies published up to Sept 2008. The initial search retrieved 468 potentially eligible studies, including four systematic reviews and eight original studies of the impact of interventions to increase demand for vaccination. We identified only two randomised controlled trials. Interventions with an impact on vaccination uptake included knowledge translation (KT) (mass media, village resource rooms and community discussions) and non-KT initiatives (incentives, economic empowerment, household visits by extension workers). Most claimed to increase vaccine coverage by 20 to 30%. Estimates of the cost per vaccinated child varied considerably with several in the range of $10-20 per vaccinated child. Most studies reviewed here represented a low level of evidence. Mass media campaigns may be effective, but the impact depends on access to media and may be costly if run at a local level. The persistence of positive effects has not been investigated. The economics of demand side interventions have not been adequately assessed, but available data suggest that some may be very cost-effective.

  10. Increased liver pathology in hepatitis C virus transgenic mice expressing the hepatitis B virus X protein

    SciTech Connect

    Keasler, Victor V.; Lerat, Herve; Madden, Charles R.; Finegold, Milton J.; McGarvey, Michael J.; Mohammed, Essam M.A.; Forbes, Stuart J.; Lemon, Stanley M.; Hadsell, Darryl L.; Grona, Shala J.; Hollinger, F. Blaine; Slagle, Betty L. . E-mail: bslagle@bcm.edu

    2006-04-10

    Transgenic mice expressing the full-length HCV coding sequence were crossed with mice that express the HBV X gene-encoded regulatory protein HBx (ATX mice) to test the hypothesis that HBx expression accelerates HCV-induced liver pathogenesis. At 16 months (mo) of age, hepatocellular carcinoma was identified in 21% of HCV/ATX mice, but in none of the single transgenic animals. Analysis of 8-mo animals revealed that, relative to HCV/WT mice, HCV/ATX mice had more severe steatosis, greater liver-to-body weight ratios, and a significant increase in the percentage of hepatocytes staining for proliferating cell nuclear antigen. Furthermore, primary hepatocytes from HCV, ATX, and HCV/ATX transgenic mice were more resistant to fas-mediated apoptosis than hepatocytes from nontransgenic littermates. These results indicate that HBx expression contributes to increased liver pathogenesis in HCV transgenic mice by a mechanism that involves an imbalance in hepatocyte death and regeneration within the context of severe steatosis.

  11. Increasing Whole Grain Intake as Part of Prevention and Treatment of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Ross, Alastair B.; Godin, Jean-Philippe; Minehira, Kaori; Kirwan, John P.

    2013-01-01

    In conjunction with the rise in rates of obesity, there has been an increase in the rate of nonalcoholic fatty liver disease (NAFLD). While NAFLD at least partially originates from poor diet, there is a lack of nutritional recommendations for patients with suspected or confirmed diagnosis of NAFLD, beyond eating a healthy diet, increasing physical activity, and emphasising weight loss. The limited current literature suggests that there may be opportunities to provide more tailored dietary advice for people diagnosed with or at risk of NAFLD. Epidemiological studies consistently find associations between whole grain intake and a reduced risk of obesity and related diseases, yet no work has been done on the potential of whole grains to prevent and/or be a part of the treatment for fatty liver diseases. In this review, we examine the potential and the current evidence for whole grains having an impact on NAFLD. Due to their nutrient and phytochemical composition, switching from consuming mainly refined grains to whole grains should be considered as part of the nutritional guidelines for patients diagnosed with or at risk for fatty liver disease. PMID:23762052

  12. Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity

    PubMed Central

    Scott, Frank I; Horton, Daniel B.; Mamtani, Ronac; Haynes, Kevin; Goldberg, David S; Lee, Dale Y.; Lewis, James D

    2016-01-01

    Background & Aims Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years. Methods We performed a retrospective cohort study of 21,714 children in The Health Improvement Network —a population-representative dataset of more than 10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling. Results In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR]=1.21; 95% confidence interval [CI], 1.07–1.38). Odds ratios increased with repeated exposures: for 1–2 prescriptions, OR=1.07 (95% CI, 0.91–1.23); for 3–5 prescriptions, OR=1.41 (95% CI, 1.20–1.65); for 6 or more prescriptions, OR=1.47 (95% CI, 1.19–1.82). Antifungal agents were not associated with obesity (OR=0.81; 95% CI, 0.59–1.11). Conclusions Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity. PMID:27003602

  13. Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity.

    PubMed

    Scott, Frank I; Horton, Daniel B; Mamtani, Ronac; Haynes, Kevin; Goldberg, David S; Lee, Dale Y; Lewis, James D

    2016-07-01

    Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years. We performed a retrospective cohort study of 21,714 children in The Health Improvement Network-a population-representative dataset of >10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling. In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.07-1.38). ORs increased with repeated exposures: for 1-2 prescriptions, OR = 1.07 (95% CI, 0.91-1.23); for 3-5 prescriptions, OR = 1.41 (95% CI, 1.20-1.65); and for 6 or more prescriptions, OR = 1.47 (95% CI, 1.19-1.82). Antifungal agents were not associated with obesity (OR = 0.81; 95% CI, 0.59-1.11). Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Online course increases nutrition professionals' knowledge, skills, and self-efficacy in using an ecological approach to prevent childhood obesity.

    PubMed

    Stark, Christina M; Graham-Kiefer, Meredith L; Devine, Carol M; Dollahite, Jamie S; Olson, Christine M

    2011-01-01

    To assess the impact of an online continuing education course on the knowledge, skills, and self-efficacy of nutrition professionals to use an ecological approach to prevent childhood obesity. Quasi-experimental design using intervention and delayed intervention comparison groups with pre/post-course assessments. Online continuing education course. Nutrition and health professionals in an online course (n = 105) and a delayed intervention comparison group (n = 37). A 6-week, facilitated online course titled, Preventing Childhood Obesity: An Ecological Approach. Changes in knowledge, skills, and self-efficacy in using an ecological approach to address childhood obesity. Paired and independent sample t tests, factor analysis, regression analysis. In contrast to a comparison group, nutrition and health professionals who participated in a 6-week online course had statistically significant increases (P < .01) in their knowledge, skills, and self-efficacy related to using an ecological approach to prevent childhood obesity. A facilitated online course can be effective at increasing the knowledge, skills, and self-efficacy of community-based nutrition and health professionals in using an ecological approach to prevent childhood obesity in their communities. Copyright © 2011 Society for Nutrition Education. Published by Elsevier Inc. All rights reserved.

  15. Sub-chronically exposing mice to a polycyclic aromatic hydrocarbon increases lipid accumulation in their livers.

    PubMed

    Jin, Yuanxiang; Miao, Wenyu; Lin, Xiaojian; Wu, Tao; Shen, Hangjie; Chen, Shan; Li, Yanhong; Pan, Qiaoqiao; Fu, Zhengwei

    2014-09-01

    The potential for exposing humans and wildlife to environmental polycyclic aromatic hydrocarbons (PAHs) has increased. Risk assessments describing how PAHs disturb lipid metabolism and induce hepatotoxicity have only received limited attention. In the present study, seven-week-old male ICR mice received intraperitoneal injections of 0, 0.01, 0.1 or 1mg/kg body weight 3-methylcholanthrene (3MC) per week for 10 weeks. A high-fat diet was provided during the exposure. Histopathological lipid accumulation and lipid metabolism-related genes were measured. We observed that sub-chronic 3MC exposure significantly increased lipid droplet and triacylglycerol (TG) levels in the livers. A low dose of 3MC activated the aryl hydrocarbon receptor, which negatively regulated lipid synthesis in the livers. The primary genes including acetyl-CoA carboxylase (Acc), fatty acid synthase (Fas) and stearoyl-CoA desaturase 1 (Scd1) decreased significantly when compared with those in the control group, indicating that de novo fatty acid synthesis in the hepatocytes was significantly inhibited by the sub-chronic 3MC exposure. However, the free fatty acid (FFA) synthesis in the adipose tissue was greatly enhanced by up-regulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and sterol regulatory element binding protein-1c (SREBP1C) and target genes including Acc, Fas and Scd1. The synthesized FFA was released into the blood and then transported into the liver by the up-regulation of Fat and Fatp2, which resulted in the gradual accumulation of lipids in the liver. In conclusion, histological examinations and molecular level analyses highlighted the development of lipid accumulation and confirmed that 3MC significantly impaired lipid metabolism in mice.

  16. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy.

    PubMed

    Yang, Lili; Rozenfeld, Raphael; Wu, Defeng; Devi, Lakshmi A; Zhang, Zhenfeng; Cederbaum, Arthur

    2014-03-01

    Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy.

  17. Increase of hepatic fat accumulation by liver specific expression of Hepatitis B virus X protein in zebrafish.

    PubMed

    Shieh, Yun-Sheng; Chang, Yin-Shan; Hong, Jiann-Ruey; Chen, Li-Je; Jou, Luen-Kuang; Hsu, Chia-Chun; Her, Guor Mour

    2010-07-01

    The pathogenesis of fatty liver disease remains largely unknown. Here, we assessed the importance of hepatic fat accumulation on the progression of hepatitis in zebrafish by liver specific expression of Hepatitis B virus X protein (HBx). Transgenic zebrafish lines, GBXs, which selectively express the GBx transgene (GFP-fused HBx gene) in liver, were established. GBX Liver phenotypes were evaluated by histopathology and molecular analysis of fatty acid (FA) metabolism-related genes expression. Most GBXs (66-81%) displayed obvious emaciation starting at 4 months old. Over 99% of the emaciated GBXs developed hepatic steatosis or steatohepatitis, which in turn led to liver hypoplasia. The liver histology of GBXs displayed steatosis, lobular inflammation, and balloon degeneration, similar to non-alcoholic steatohepatitis (NASH). Oil red O stain detected the accumulation of fatty droplets in GBXs. RT-PCR and Q-rt-PCR analysis revealed that GBx induced hepatic steatosis had significant increases in the expression of lipogenic genes, C/EBP-alpha, SREBP1, ChREBP and PPAR-gamma, which then activate key enzymes of the de novo FA synthesis, ACC1, FAS, SCD1, AGAPT, PAP and DGAT2. In addition, the steatohepatitic GBX liver progressed to liver degeneration and exhibited significant differential gene expression in apoptosis and stress. The GBX models exhibited both the genetic and functional factors involved in lipid accumulation and steatosis-associated liver injury. In addition, GBXs with transmissible NASH-like phenotypes provide a promising model for studying liver disease.

  18. Increased beta-aminoisobutyric acid in rat liver with 6-azauracil and its enantiomer.

    PubMed

    Tamaki, N; Fujimoto, S; Mizutani, N; Mizota, C

    1985-10-21

    When 6-azauracil was subcutaneously injected, beta-aminoisobutyric acid and beta-alanine contents were increased 22 and 61-fold, respectively, in rat liver. Incorporation of [methyl-14C]thymine into beta-aminoisobutyric acid was increased to 42-fold by 6-azauracil treatment. The absolute configuration of this amino acid was proved to be the (R)-form by means of a gas-chromatographic technique. 6-Azauracil inhibited beta-alanine-pyruvate aminotransferase activity with an I50 of approx. 2.5 mM.

  19. Administration of Escherichia coli endotoxin to rat increases liver mass and hepatocyte volume in vivo.

    PubMed Central

    Qian, D; Brosnan, J T

    1996-01-01

    We have established, in vivo, an increase in liver mass and hepatocyte volume after a single intraperitoneal administration, to fasted rats, of Escherichia coli lipopolysaccharide (0127:B8) at 3 mg/kg. The phenomenon was time- and dose-dependent and could be prevented by treatment with polyclonal antiserum against tumour necrosis factor-alpha (TNF-alpha) before the endotoxin injection. Endotoxin caused an increase of 26% in the hepatic mass compared with fasted controls at 24 h. An increase of 27% in the hepatic water content underlay the altered hepatic mass which could not be accounted for by a change in the volume of hepatic blood and/or interstitial fluid (measured in vivo), suggesting an expansion in the hepatocellular volume. This is supported by an increase of 25% in the K+ content of the endotoxic livers. Morphometric study confirmed a 15% increase in hepatocyte volume after endotoxin administration. The data are discussed in the light of possible metabolic effects of increased hepatocyte volume. PMID:8573081

  20. Increasing Availability of Exposure Therapy Through Intensive Group Treatment for Childhood Anxiety and OCD.

    PubMed

    Whiteside, Stephen P H; Dammann, Julie E; Tiede, Michael S; Biggs, Bridget K; Hillson Jensen, Andrea

    2017-09-01

    Archival data were used to examine the feasibility of a 5-day, clinic-based, intensive exposure-based cognitive-behavioral group therapy for childhood anxiety disorders (CADs) and obsessive-compulsive disorder (OCD). Participants were 143 children (82 girls) aged 6 to 19 years ( M = 13.93 years, SD = 2.9 years) with CADs or OCD (or both) in 28 consecutive groups. Repeated-measures ANOVA in the subsample ( n = 57) with complete treatment data indicated positive change on all variables from pretreatment to posttreatment with few differences between CADs and OCD patients. Effect sizes were moderate to large for anxiety symptoms (parent reported = 0.74, child reported = 0.65) and impairment (parent reported = 1.02, child reported = 0.69). The intensive group protocol required fewer sessions and 36% fewer therapist-hours per patient than the individually administered protocol. The program increased treatment availability for families from diverse geographic areas ( M distance traveled to clinic = 407 miles, SD = 786.4 miles). These findings support further, well-controlled examination of the 5-day intensive group treatment protocol's efficacy and potential to increase availability of evidence-based exposure therapy.

  1. Childhood onset generalised dystonia can be modelled by increased gain in the indirect basal ganglia pathway.

    PubMed

    Sanger, T D

    2003-11-01

    Clinical experience suggests an important role of the indirect basal ganglia pathway in the genesis of childhood onset generalised dystonia, but it has been difficult to reconcile the increased muscle activity in dystonia with the current model of basal ganglia function in which the indirect pathway is considered primarily inhibitory. The aim of this study was to present a modification of the direct-indirect pathway model, in which the indirect pathway is inverting rather than purely inhibitory, so that while high signals are inhibited, low signals are amplified. As the basal ganglia may be a feedback loop that modifies cortical activity, instability from excessive gain in this feedback loop could explain features of dystonia. A detailed mathematical model is provided, together with simulations of cortical cell population spiking behaviour when connected through a basal ganglia loop. The simulations show that increased gain in the indirect pathway relative to the direct pathway can lead to unstable uncontrolled synchronous oscillations in cortex and basal ganglia. This behaviour could result in dystonia. The model provides a consistent explanation for the association of dystonia with parkinsonism and disorders characterised by dopamine depletion, the ability to treat some dystonias with dopamine, the ability of neuroleptic drug treatment to cause an acute dystonic reaction treatable with anticholinergic drugs, and the ability of pallidotomy or deep brain stimulation of the internal pallidum to alleviate symptoms of generalised dystonia.

  2. Increased sensitivity of apolipoprotein E knockout mice to copper-induced oxidative injury to the liver.

    PubMed

    Chen, Yuan; Li, Bin; Zhao, Ran-ran; Zhang, Hui-feng; Zhen, Chao; Guo, Li

    2015-04-10

    Apolipoprotein E (ApoE) genotypes are related to clinical presentations in patients with Wilson's disease, indicating that ApoE may play an important role in the disease. However, our understanding of the role of ApoE in Wilson's disease is limited. High copper concentration in Wilson's disease induces excessive generation of free oxygen radicals. Meanwhile, ApoE proteins possess antioxidant effects. We therefore determined whether copper-induced oxidative damage differ in the liver of wild-type and ApoE knockout (ApoE(-/-)) mice. Both wild-type and ApoE(-/-) mice were intragastrically administered with 0.2 mL of copper sulfate pentahydrate (200 mg/kg; a total dose of 4 mg/d) or the same volume of saline daily for 12 weeks, respectively. Copper and oxidative stress markers in the liver tissue and in the serum were assessed. Our results showed that, compared with the wild-type mice administered with copper, TBARS as a marker of lipid peroxidation, the expression of oxygenase-1 (HO-1), NAD(P)H dehydrogenase, and quinone 1 (NQO1) significantly increased in the ApoE(-/-) mice administered with copper, meanwhile superoxide dismutase (SOD) activity significantly decreased. Thus, it is concluded that ApoE may protect the liver from copper-induced oxidative damage in Wilson's disease.

  3. Are Children Born with Birth Defects at Increased Risk of Injuries in Early Childhood?

    PubMed

    Rutkowski, Rachel E; Salemi, Jason L; Tanner, Jean Paul; Anjohrin, Suzanne; Cavicchia, Philip; Lake-Burger, Heather; Kirby, Russell S

    2017-09-01

    To investigate the extent to which children with birth defects experience differential likelihood of various injuries and injury-related hospitalizations in early childhood. The Florida Birth Defects Registry was used to identify infants born 2006-2010 with select birth defects. Injury matrices were used to detect injuries in inpatient, ambulatory, and emergency department admissions for each infant up to their third birthday. χ(2)tests were used to compare sociodemographic and perinatal characteristics of children, by presence of an injury-related hospital admission. Adjusted multivariable logistic and zero-inflated negative binomial regression models were used to investigate birth defect and injury associations and related hospital use. We observed a 21% (99% CI: 1.16-1.27) increased odds of injury in children with birth defects. All birth defect subgroups had a statistically significantly increased odds of injury (excluding chromosomal defects), with adjusted ORs ranging from 1.19 to 1.40. The combination of birth defects and injuries resulted in 40% (99% CI: 1.36-1.44) more frequent injury-related hospital visits and a 3-fold (99% CI: 2.76-2.96) increase in time spent receiving inpatient medical care. Over 30% of children with critical congenital heart defects had an injury-related hospital admission. Children born with specific birth defects are at increased likelihood of various injuries during early life. Although the magnitude of this increased likelihood varied by the mechanism by which the injury occurred, the location of the injury, and the type of birth defect, our study findings support a direct association between birth defects and injuries in early life. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease.

    PubMed

    Pacifico, Lucia; Bonci, Enea; Marandola, Lidia; Romaggioli, Sara; Bascetta, Stefano; Chiesa, Claudio

    2014-12-07

    To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD). A case-control study was performed. Cases were 40 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (HFF ≥ 5%), and confirmed by liver biopsy with ≥ 5% of hepatocytes containing macrovesicular fat. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1) with the cases on age, gender, pubertal stage and as closely as possible on body mass index- standard deviation score. All participants underwent clinical examination, laboratory tests including zonulin, inflammatory and metabolic parameters, and MRI for measurement of HFF and visceral adipose tissue. Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD [median (interquartile range), 4.23 (3.18-5.89) vs 3.31 (2.05-4.63), P < 0.01]. In patients with NAFLD, zonulin concentrations increased significantly with the severity of steatosis and the Spearman's coefficient revealed a positive correlation between zonulin values and steatosis (r = 0.372, P < 0.05); however, we did not find a significant correlation between zonulin and lobular inflammation (P = 0.23), ballooning (P = 0.10), fibrosis score (P = 0.18), or presence of nonalcoholic steatohepatitis (P = 0.17). Within the entire study population, zonulin levels were positively associated with gamma-glutamyl transferase, 2-h insulin, HFF, and negatively associated with whole-body insulin sensitivity index (WBISI), after adjustment for age, gender and pubertal status. When the associations were restricted to the group of NAFLD patients, 2-h insulin, hepatic fat, and WBISI retained statistical significance. Circulating

  5. Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease

    PubMed Central

    Pacifico, Lucia; Bonci, Enea; Marandola, Lidia; Romaggioli, Sara; Bascetta, Stefano; Chiesa, Claudio

    2014-01-01

    AIM: To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD). METHODS: A case-control study was performed. Cases were 40 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (HFF ≥ 5%), and confirmed by liver biopsy with ≥ 5% of hepatocytes containing macrovesicular fat. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1) with the cases on age, gender, pubertal stage and as closely as possible on body mass index- standard deviation score. All participants underwent clinical examination, laboratory tests including zonulin, inflammatory and metabolic parameters, and MRI for measurement of HFF and visceral adipose tissue. RESULTS: Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD [median (interquartile range), 4.23 (3.18-5.89) vs 3.31 (2.05-4.63), P < 0.01]. In patients with NAFLD, zonulin concentrations increased significantly with the severity of steatosis and the Spearman’s coefficient revealed a positive correlation between zonulin values and steatosis (r = 0.372, P < 0.05); however, we did not find a significant correlation between zonulin and lobular inflammation (P = 0.23), ballooning (P = 0.10), fibrosis score (P = 0.18), or presence of nonalcoholic steatohepatitis (P = 0.17). Within the entire study population, zonulin levels were positively associated with gamma-glutamyl transferase, 2-h insulin, HFF, and negatively associated with whole-body insulin sensitivity index (WBISI), after adjustment for age, gender and pubertal status. When the associations were restricted to the group of NAFLD patients, 2-h insulin, hepatic fat, and WBISI retained statistical

  6. Late effects of childhood cancer treatment: severe hypertriglyceridaemia, central obesity, non alcoholic fatty liver disease and diabetes as complications of childhood total body irradiation.

    PubMed

    Rajendran, R; Abu, E; Fadl, A; Byrne, C D

    2013-08-01

    Childhood cancer survivors may develop a number of endocrine complications linked to organ failure, such as hypogonadism, diabetes and growth hormone deficiency. However, increasing evidence now suggests that total body irradiation treatment, specifically, is linked with future risk of insulin resistance, hepatic steatosis and dyslipidaemia, possibly because total body irradiation affects adipocyte differentiation and impairs subcutaneous adipose tissue depot expansion during times of positive energy balance. We describe a 20-year-old woman who developed pancreatitis with severe hypertriglyceridaemia (serum triglycerides > 300 mmol/l) that required plasmapheresis. She had received total body irradiation prior to her bone marrow transplant at age 6 years for relapsed acute lymphoblastic leukaemia. She developed ovarian failure at age 12 years. At age 15 years she was noted to have hyperglycaemia, increased blood pressure, hepatic steatosis and mild hypertriglyceridaemia. She presented with severe hypertriglyceridaemia and eruptive xanthoma, and developed pancreatitis 12 h after admission. She was treated with plasmapheresis and intravenous insulin and made an excellent recovery. We implicate and discuss total body irradiation as the major contributing factor to her severe hypertriglyceridaemia, compounded by worsening glycaemic control, oestrogen deficiency and a changing adult lifestyle. Children who have received total body irradiation are at risk of diabetes and an exaggerated form of the metabolic syndrome with hypertriglyceridaemia, which can be life-threatening. We suggest that survivors of total body irradiation treatment require careful lifelong monitoring of their metabolic status. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  7. Activation of liver X receptor increases acetaminophen clearance and prevents its toxicity in mice.

    PubMed

    Saini, Simrat P S; Zhang, Bin; Niu, Yongdong; Jiang, Mengxi; Gao, Jie; Zhai, Yonggong; Hoon Lee, Jung; Uppal, Hirdesh; Tian, Hui; Tortorici, Michael A; Poloyac, Samuel M; Qin, Wenxin; Venkataramanan, Raman; Xie, Wen

    2011-12-01

    Overdose of acetaminophen (APAP), the active ingredient of Tylenol, is the leading cause of drug-induced acute liver failure in the United States. As such, it is necessary to develop novel strategies to prevent or manage APAP toxicity. In this report, we reveal a novel function of the liver X receptor (LXR) in preventing APAP-induced hepatotoxicity. Activation of LXR in transgenic (Tg) mice or by an LXR agonist conferred resistance to the hepatotoxicity of APAP, whereas the effect of LXR agonist on APAP toxicity was abolished in LXR-deficient mice. The increased APAP resistance in LXR Tg mice was associated with increased APAP clearance, increased APAP sulfation, and decreased formation of toxic APAP metabolites. The hepatoprotective effect of LXR may have resulted from the induction of antitoxic phase II conjugating enzymes, such as Gst and Sult2a1, as well as the suppression of protoxic phase I P450 enzymes, such as Cyp3a11 and Cyp2e1. Promoter analysis suggested the mouse Gst isoforms as novel transcriptional targets of LXR. The suppression of Cyp3a11 may be accounted for by the inhibitory effect of LXR on the PXR-responsive transactivation of Cyp3a11. The protective effect of LXR in preventing APAP toxicity is opposite to the sensitizing effect of pregnane X receptor, constitutive androstane receptor, and retinoid X receptor alpha. We conclude that LXR represents a potential therapeutic target for the prevention and treatment of Tylenol toxicity. Copyright © 2011 American Association for the Study of Liver Diseases.

  8. Does childhood victimization increase the risk of early death? A 25-year prospective study.

    PubMed

    White, Helene Raskin; Widom, Cathy Spatz

    2003-07-01

    Abuse and neglect have been shown to influence the mental and physical health of children; however, few studies have examined whether childhood victimization leads to an increased risk of early death. This paper compares mortality data and examines cause of death for a sample of 908 abused and/or neglected individuals and 667 matched controls who were followed up into young adulthood. Using data from a prospective cohort design study, a large group of children with substantiated cases of abuse (physical and sexual) and/or neglect approximately 25 years ago were matched with a control group of children and both groups were followed up into adulthood. The National Death Index was searched twice and official death certificates were collected for most individuals who had died. Surprisingly, there were no significant differences in rates of mortality for the two groups (abuse and neglect = 3.5%, controls = 3.0%). Furthermore, victims of child abuse and neglect were not more likely to experience a violent death. Our results do not provide support for a heightened rate of early death in abused and neglected children followed up into young adulthood. Limitations of the study are discussed as well as potential reasons for these unexpected findings.

  9. Childhood Exposure to Secondhand Smoke and Functional Mannose Binding Lectin Polymorphisms Are Associated with Increased Lung Cancer Risk

    PubMed Central

    Olivo-Marston, Susan E.; Yang, Ping; Mechanic, Leah E.; Bowman, Elise D.; Pine, Sharon R.; Loffredo, Christopher A.; Alberg, Anthony J.; Caporaso, Neil; Shields, Peter G.; Chanock, Stephen; Wu, Yanhong; Jiang, Ruoxiang; Cunningham, Julie; Jen, Jin; Harris, Curtis C.

    2010-01-01

    Background Exposure to secondhand smoke during adulthood has detrimental health effects, including increased lung cancer risk. Compared with adults, children may be more susceptible to secondhand smoke. This susceptibility may be exacerbated by alterations in inherited genetic variants of innate immunity genes. We hypothesized a positive association between childhood secondhand smoke exposure and lung cancer risk that would be modified by genetic polymorphisms in the mannose binding lectin-2 (MBL2) gene resulting in well-known functional changes in innate immunity. Methods Childhood secondhand smoke exposure and lung cancer risk was assessed among men and women in the ongoing National Cancer Institute-Maryland Lung Cancer (NCI-MD) study, which included 624 cases and 348 controls. Secondhand smoke history was collected via in-person interviews. DNA was used for genotyping the MBL2 gene. To replicate, we used an independent case-control study from Mayo Clinic consisting of 461 never smokers, made up of 172 cases and 289 controls. All statistical tests were two-sided. Results In the NCI-MD study, secondhand smoke exposure during childhood was associated with increased lung cancer risk among never smokers [odds ratio (OR), 2.25; 95% confidence interval (95% CI), 1.04-4.90]. This was confirmed in the Mayo study (OR, 1.47; 95% CI, 1.00-2.15). A functional MBL2 haplotype associated with high circulating levels of MBL and increased MBL2 activity was associated with increased lung cancer risk among those exposed to childhood secondhand smoke in both the NCI-MD and Mayo studies (OR, 2.52; 95% CI, 1.13-5.60, and OR, 2.78; 95% CI, 1.18-3.85, respectively). Conclusions Secondhand smoke exposure during childhood is associated with increased lung cancer risk among never smokers, particularly among those possessing a haplotype corresponding to a known overactive complement pathway of the innate immune system. PMID:19959685

  10. Childhood exposure to secondhand smoke and functional mannose binding lectin polymorphisms are associated with increased lung cancer risk.

    PubMed

    Olivo-Marston, Susan E; Yang, Ping; Mechanic, Leah E; Bowman, Elise D; Pine, Sharon R; Loffredo, Christopher A; Alberg, Anthony J; Caporaso, Neil; Shields, Peter G; Chanock, Stephen; Wu, Yanhong; Jiang, Ruoxiang; Cunningham, Julie; Jen, Jin; Harris, Curtis C

    2009-12-01

    Exposure to secondhand smoke during adulthood has detrimental health effects, including increased lung cancer risk. Compared with adults, children may be more susceptible to secondhand smoke. This susceptibility may be exacerbated by alterations in inherited genetic variants of innate immunity genes. We hypothesized a positive association between childhood secondhand smoke exposure and lung cancer risk that would be modified by genetic polymorphisms in the mannose binding lectin-2 (MBL2) gene resulting in well-known functional changes in innate immunity. Childhood secondhand smoke exposure and lung cancer risk was assessed among men and women in the ongoing National Cancer Institute-Maryland Lung Cancer (NCI-MD) study, which included 624 cases and 348 controls. Secondhand smoke history was collected via in-person interviews. DNA was used for genotyping the MBL2 gene. To replicate, we used an independent case-control study from Mayo Clinic consisting of 461 never smokers, made up of 172 cases and 289 controls. All statistical tests were two-sided. In the NCI-MD study, secondhand smoke exposure during childhood was associated with increased lung cancer risk among never smokers [odds ratio (OR), 2.25; 95% confidence interval (95% CI), 1.04-4.90]. This was confirmed in the Mayo study (OR, 1.47; 95% CI, 1.00-2.15). A functional MBL2 haplotype associated with high circulating levels of MBL and increased MBL2 activity was associated with increased lung cancer risk among those exposed to childhood secondhand smoke in both the NCI-MD and Mayo studies (OR, 2.52; 95% CI, 1.13-5.60, and OR, 2.78; 95% CI, 1.18-3.85, respectively). Secondhand smoke exposure during childhood is associated with increased lung cancer risk among never smokers, particularly among those possessing a haplotype corresponding to a known overactive complement pathway of the innate immune system.

  11. Cortisol administration increases hippocampal activation to infant crying in males depending on childhood neglect.

    PubMed

    Bos, Peter A; Montoya, Estrella R; Terburg, David; van Honk, Jack

    2014-10-01

    Animal studies show that exposure to parental neglect alters stress regulation and can lead to neural hyposensitivity or hypersensitivity in response to cortisol, most pronounced in the hippocampus. Cortisol, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, has also been related to parenting more directly, for example, in both sexes, cortisol levels increase when listening to infants crying, possibly to activate and facilitate effective care behavior. Severe trauma is known to negatively affect the HPA-axis in humans; however, it is unknown whether normal variation in parental care in the healthy population can alter sensitivity of the hippocampus to cortisol. Here, we investigate whether variation in experienced neglect changes neural sensitivity to cortisol when humans listen to infant crying, which is an unequivocal signal relevant for care behavior. In a placebo-controlled, within-subject neuroimaging study, we administered 40 mg cortisol to 21 healthy young males without children and used a validated task for measuring neural responses to infant crying. The Dutch version of the Childhood Trauma Questionnaire was used to index participants' early exposure to abuse and neglect. The data show that cortisol markedly increased hippocampal activation toward crying infants, and this effect varied significantly with parental neglect, even in our nonclinical subject sample. Without exposure to severe trauma or neglect, reduced self-experienced quality of parental care in the normal range already substantially increased hippocampal responsivity to cortisol. Altered hippocampal sensitivity to cortisol might be a cross-species marker for the risk of developing later life psychopathology.

  12. Steatohepatitis is developed by a diet high in fat, sucrose, and cholesterol without increasing iron concentration in rat liver.

    PubMed

    Takai, Katsuko; Funaba, Masayuki; Matsui, Tohru

    2016-04-01

    Iron overload to the liver is known to be a pathogenesis of nonalcoholic steatohepatitis through oxidative stress. High-fat diets have been reported to increase iron concentration in livers that developed steatohepatitis in experimental animals. However, the effect of high-fat diets on hepatic iron concentration is controversial. We hypothesized that a diet high in lard, cholesterol, and sucrose (Western diet) leads to the development of steatohepatitis without increasing hepatic iron concentration. Rats were given either a control or the Western diet for 12 weeks. The Western diet increased triacylglycerol concentration and oxidative stress markers such as the concentration of thiobarbituric acid reactive substances and messenger RNA (mRNA) expression of heme oxygenase-1 in the liver. The Western diet also increased the mRNA expression of macrophage-1 antigen, cluster of differentiation (CD) 45, and CD68 in the liver, and nuclear factor κB level in liver nuclear fraction, suggesting the development of hepatic inflammation. Histological observation also indicated fatty liver and hepatic inflammation in the rats given the Western diet. In contrast, the Western diet decreased iron concentration in the liver. These results clearly indicated that the diet high in lard, cholesterol, and sucrose induces steatohepatitis without increasing hepatic iron concentration.

  13. Immigrating to Canada During Early Childhood Associated with Increased Risk for Mood Disorders.

    PubMed

    Islam, Farah

    2015-08-01

    This study explored the impact of age at time of immigration on mental health in Canada. The Canadian Community Health Survey (CCHS) 2011 was analyzed to determine prevalence rates for mood disorders for those who immigrated during early childhood, middle childhood, adolescence, and adulthood. Multivariable logistic regression analysis was carried out on pooled CCHS 2007-2011 data to calculate risk of mood disorders. Those who immigrated during early childhood (before the age of six) had a significantly higher prevalence rate of mood disorders (6.83 %, 95 % CI 6.77-6.89) compared to those who immigrated later in life (4.83-4.88 %, 95 % CI 4.56-4.93). Immigrating during early childhood was also associated with elevated risk of mood disorders (OR 1.40, 95 % CI 1.04-1.88) compared to those who immigrated as adults after adjusting for key factors. Mental health services need to consider the factors associated with early childhood migration and the implications for early intervention programming.

  14. Utilization of Public Health Service Increased Risk Donors Yields Equivalent Outcomes in Liver Transplantation.

    PubMed

    Fleetwood, V A; Lusciks, J; Poirier, J; Hertl, M; Chan, E Y

    2016-01-01

    Background. The PHS increased risk donor (IRD) is underutilized in liver transplantation. We aimed to examine the posttransplant outcomes in recipients of increased-risk organs. Methods. We analyzed 228,040 transplants in the Organ Procurement and Transplantation Network database from 2004 to 2013. Endpoints were graft failure and death. Results were controlled for demographics and comorbidities. Statistical analysis utilized Fisher's test and logistic regression. Results. 58,816 patients were identified (5,534 IRD, 53,282 non-IRD). IRDs were more frequently male (69.2% versus 58.3%, p < 0.001), younger (34 versus 39, p < 0.001), and less likely to have comorbidities (p < 0.001). Waitlist time was longer for IRD graft recipients (254 versus 238 days, p < 0.001). All outcomes were better in the IRD group. Graft failure (23.6 versus 27.3%, p < 0.001) and mortality (20.4 versus 22.3%, p = 0.001) were decreased in IRD graft recipients. However, in multivariate analysis, IRD status was not a significant indicator of outcomes. Conclusion. This is the first study to describe IRD demographics in liver transplantation. Outcomes are improved in IRD organ recipients; however, controlling for donor and recipient comorbidities, ischemia time, and MELD score, the differences lose significance. In multivariate analysis, use of IRD organs is noninferior, with similar graft failure and mortality despite the infectious risk.

  15. Donor Liver Small Droplet Macrovesicular Steatosis Is Associated With Increased Risk for Recipient Allograft Rejection.

    PubMed

    Choi, Won-Tak; Jen, Kuang-Yu; Wang, Dongliang; Tavakol, Mehdi; Roberts, John P; Gill, Ryan M

    2017-03-01

    Although donor livers with <30% large droplet macrovesicular steatosis (MaS) and/or small droplet MaS (irrespective of percentage) are considered safe to use, this consensus is based on variable definitions of MaS subtypes and/or without a reproducible scoring system. We analyzed 134 donor liver biopsies from allografts transplanted at University of California at San Francisco between 2000 and 2015 to determine whether large and/or small droplet MaS is a risk factor for poor outcomes. Large droplet MaS was defined as a fat droplet occupying greater than one half of an individual hepatocyte, with nuclear displacement, and scored as the percentage of total parenchymal area replaced by large fat droplets on ×40 magnification. Small droplet MaS was defined as 1 to several discrete fat droplets, each occupying less than one half of an individual hepatocyte, and scored as the percentage of remaining hepatocytes (ie, hepatocytes not occupied by large fat droplets) containing small fat droplets on ×200 magnification (ie, small droplet MaS is the percentage of "remaining hepatocytes" with small fat droplets, and "remaining hepatocytes" is defined as 100% minus percent large droplet MaS). Thus, total MaS equals the sum of large and small droplet MaS, which cannot exceed 100%. Electronic medical records were reviewed to determine outcomes. There was an increased risk for acute cellular rejection (hazard ratio=2.5, P=0.0108) and bile duct loss suggestive of chronic ductopenic rejection (hazard ratio=2.4, P=0.0130) in donor livers with ≥30% small droplet MaS. Large droplet MaS (up to 60%) was not associated with adverse outcomes. Patient survival was not adversely affected by steatosis. Excellent agreement on the estimation of large (weighted κ=0.682) and small droplet MaS (weighted κ=0.780) was achieved. Our approach to donor steatosis scoring can identify liver allograft recipients at increased risk for rejection and highlights the importance of distinguishing between

  16. Bactericidal/permeability-increasing protein preserves leukocyte functions after major liver resection.

    PubMed

    Wiezer, M J; Meijer, C; Sietses, C; Prins, H A; Cuesta, M A; Beelen, R H; Meijer, S; van Leeuwen, P A

    2000-08-01

    To analyze postoperative leukocyte functions in patients undergoing hemihepatectomy, and to assess the effect of treatment with the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21). Extensive liver resection is associated with a high incidence of infectious complications. Because elimination of pathogenic microorganisms occurs mainly by leukocytes, this increased rate of infections is most likely due to an impaired function of these cells. Endotoxin, translocated from the gut into the systemic circulation as a result of increased gut permeability and reduced hepatic clearance function after major liver resection, may play an important role in the impairment of posthepatectomy leukocyte function. To investigate whether hemihepatectomy results in impaired leukocyte functions and to determine the role of endotoxin in this process, leukocyte oxidative burst and leukocyte antigen expression were studied in three groups of patients: patients undergoing a hemihepatectomy and receiving rBPI21 treatment, patients undergoing hemihepatectomy and receiving placebo, and as an extra control group patients undergoing other major abdominal surgeries. Blood samples were collected before surgery, 2 hours after surgery, and at days 1, 2, 5, and 7. Phorbol myristate acetate-stimulated oxidative burst was measured using dihydrorhodamine, and leukocyte surface expression of the antigens CD11b, CD16, and CD14 was investigated by indirect immunofluorescence. Both oxidative burst and membrane surface expression were quantified by flow cytometry. An indication of the antiendotoxin effect of rBPI21 treatment was provided by assessment of plasma lipopolysaccharide binding protein (LBP) levels by enzyme-linked immunosorbent assay. The oxidative burst in the hemihepatectomized patients receiving placebo and the controls increased 2 hours after surgery, whereas it decreased in the rBPI21-treated patients, resulting in significant differences between the groups

  17. Lack of correlation between hepatitis B virus infection and the increasing incidence of primary liver cancer in Sweden.

    PubMed

    Kaczynski, J; Hansson, G; Norkrans, G; Wallerstedt, S

    1991-01-01

    The incidence of primary carcinoma of the liver in Sweden has been reported to increase. In order to study the role of chronic hepatitis B virus (HBV) infection for liver cancer development 40 cases with hepatocellular carcinoma (HCC) were examined for the presence of HBV surface antigen and HBV core antigen in the cancer and in the surrounding non-neoplastic liver tissue. It was not possible to demonstrate a single case with tissue HBV antigen, indicating that HBV plays a minor role in the etiology of HCC in Sweden and thus does not seem to be responsible for the increasing incidence of this cancer.

  18. Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood.

    PubMed

    Bjerg, A; Ekerljung, L; Eriksson, J; Näslund, J; Sjölander, S; Rönmark, E; Dahl, Å; Holmberg, K; Wennergren, G; Torén, K; Borres, M P; Lötvall, J; Lundbäck, B

    2016-10-01

    To date, most studies of the 'allergy epidemic' have been based on self-reported data. There is still limited knowledge on time trends in allergic sensitization, especially among adults. To study allergic sensitization, its risk factors and time trends in prevalence. Within West Sweden Asthma Study (WSAS), a population-based sample of 788 adults (17-60 years) underwent skin prick tests (SPTs) for 11 aeroallergens 2009-2012. Specific IgE was analysed in 750 of the participants. Those aged 20-46 years (n = 379) were compared with the European Community Respiratory Health Survey sample aged 20-46 year from the same area (n = 591) in 1991-1992. Among those aged 20-46 years, the prevalence of positive SPT to pollen increased, timothy from 17.1% to 29.0% (P < 0.001) and birch from 15.6% to 23.7% (P = 0.002) between 1991-1992 and 2009-2012. Measurements of specific IgE confirmed these increases. Prevalence of sensitization to all other tested allergens was unchanged. In the full WSAS sample aged 17-60 years, any positive SPT was seen in 41.9%, and the dominating sensitizers were pollen (34.3%), animals (22.8%) and mites (12.6%). Pollen sensitization was strongly associated with rhinitis, whereas indoor allergens were more associated with asthma. Growing up with livestock or furred pets decreased the risk of sensitization, adjusted odds ratio 0.53 (0.28-0.995) and 0.68 (0.47-0.98), respectively. Pollen sensitization has increased in Swedish adults since the early 1990s, while the prevalence of sensitization to other allergens has remained unchanged. This is one plausible explanation for the increase in rhinitis 1990-2008 in Swedish adults, during which time the prevalence of asthma, which is more associated with perennial allergens, was stable. Contact with animals in childhood seems to reduce the risk of sensitization well into adulthood. One major factor contributing to the rise in pollen allergy is a significant increase in levels of birch and grass pollen over the past

  19. MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

    PubMed Central

    Thabet, Khaled; Asimakopoulos, Anastasia; Shojaei, Maryam; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L.; Berg, Thomas; Dore, Gregory J.; Grønbæk, Henning; Sheridan, David; Abate, Maria Lorena; Bugianesi, Elisabetta; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Fischer, Janett; Spengler, Ulrich; Nattermann, Jacob; Wahid, Ahmed; Rojas, Angela; White, Rose; Douglas, Mark W.; McLeod, Duncan; Powell, Elizabeth; Liddle, Christopher; van der Poorten, David; George, Jacob; Eslam, Mohammed; Gallego-Duran, Rocio; Applegate, Tanya; Bassendine, Margaret; Rosso, Chiara; Mezzabotta, Lavinia; Leung, Reynold; Malik, Barbara; Matthews, Gail; Grebely, Jason; Fragomeli, Vincenzo; Jonsson, Julie R.; Santaro, Rosanna

    2016-01-01

    Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis. PMID:27630043

  20. Bumetanide increases manganese accumulation in the brain of rats with liver damage.

    PubMed

    Montes, Sergio; Castro-Chávez, Armando; Florian-Soto, Circe; Heras-Romero, Yessica; Ríos, Camilo; Rivera-Mancía, Susana

    2016-03-05

    Hepatic encephalopathy is a common complication in cases of liver damage; it results from several factors, including the accumulation of toxic substances in the brain, e.g. manganese, ammonia and glutamine. We have previously reported that manganese favors ammonia and glutamine accumulation in the brain of cirrhotic rats, and we suggested that such effect could be mediated by manganese-elicited activation of the NKCC1 (Na(+)/K(+)/2Cl(-) cotransporter 1). To test this hypothesis, we used bumetanide, an NKCC1 blocker prescribed to treat ascites in cirrhotic patients; we expected that if NKCC1 was responsible for manganese-mediated ammonia buildup and the subsequent glutamine accumulation, bumetanide could counteract such effect and improve motor coordination. In addition, we considered essential to test the effect of bumetanide on manganese brain levels. We used a model of liver damage in rats, consisting in bile-duct ligation. Animals were exposed to manganese in the drinking water (1 mg/ml) for two weeks and ammonia in the food (20% w/w of ammonia acetate) during the second week after surgery. Bumetanide was administered intraperitoneally in the course of the ammonia treatment. We measured glutamine and manganese in three brain regions: frontal cortex, striatum and cerebellum. Bumetanide produced no effect on glutamine accumulation; however, because of bumetanide treatment, manganese was increased in the brain, and also the activity of gamma-glutamyl transferase in plasma; thus, we consider that the influence of bumetanide and similar diuretics on liver function and manganese homeostasis should be further studied.

  1. Childhood abuse is associated with increased hair cortisol levels among urban pregnant women

    PubMed Central

    Schreier, Hannah M C; Enlow, Michelle Bosquet; Ritz, Thomas; Gennings, Chris; Wright, Rosalind J

    2015-01-01

    Background Hypothalamic–pituitary–adrenal (HPA) axis activity is known to be altered following events such as childhood abuse. However, despite potential adverse consequences for the offspring of women who have experienced abuse, very little is known about altered HPA axis activity during pregnancy. Methods During pregnancy, 180 women from diverse racial/ethnic backgrounds reported on their exposure to emotional, physical and/or sexual abuse before the age of 11, and general post-traumatic stress symptoms (ie, not limited to childhood years or abuse experiences). Around delivery, they provided hair samples for the assessment of cortisol levels during pregnancy. Hair cortisol was assessed for each pregnancy trimester. The effect of childhood abuse on hair cortisol was assessed using mixed-effects analyses of covariance models allowing for within-subject correlated observations, and were first performed in the entire sample and subsequently stratified by race/ethnicity. Results Controlling for post-traumatic stress symptoms, hair cortisol levels varied by history of child abuse, F(2,166)=3.66, p=0.028. Childhood physical and/or sexual abuse was associated with greater hair cortisol levels, t(166)=2.65, p=0.009, compared with no history of abuse. Because childhood rates of abuse and hair cortisol levels varied by race/ethnicity, analyses were stratified by race/ethnicity. The associations between history of abuse and cortisol levels were only significant among black women, F(2,23)=5.37, p=0.012. Conclusions Childhood abuse, especially physical and/or sexual abuse, is associated with differences in cortisol production during pregnancy, particularly among black women. Future research should investigate how these differences impact physical and mental health outcomes among offspring of affected women. PMID:26219886

  2. Childhood abuse is associated with increased hair cortisol levels among urban pregnant women.

    PubMed

    Schreier, Hannah M C; Enlow, Michelle Bosquet; Ritz, Thomas; Gennings, Chris; Wright, Rosalind J

    2015-12-01

    Hypothalamic-pituitary-adrenal (HPA) axis activity is known to be altered following events such as childhood abuse. However, despite potential adverse consequences for the offspring of women who have experienced abuse, very little is known about altered HPA axis activity during pregnancy. During pregnancy, 180 women from diverse racial/ethnic backgrounds reported on their exposure to emotional, physical and/or sexual abuse before the age of 11, and general post-traumatic stress symptoms (ie, not limited to childhood years or abuse experiences). Around delivery, they provided hair samples for the assessment of cortisol levels during pregnancy. Hair cortisol was assessed for each pregnancy trimester. The effect of childhood abuse on hair cortisol was assessed using mixed-effects analyses of covariance models allowing for within-subject correlated observations, and were first performed in the entire sample and subsequently stratified by race/ethnicity. Controlling for post-traumatic stress symptoms, hair cortisol levels varied by history of child abuse, F(2,166)=3.66, p=0.028. Childhood physical and/or sexual abuse was associated with greater hair cortisol levels, t(166)=2.65, p=0.009, compared with no history of abuse. Because childhood rates of abuse and hair cortisol levels varied by race/ethnicity, analyses were stratified by race/ethnicity. The associations between history of abuse and cortisol levels were only significant among black women, F(2,23)=5.37, p=0.012. Childhood abuse, especially physical and/or sexual abuse, is associated with differences in cortisol production during pregnancy, particularly among black women. Future research should investigate how these differences impact physical and mental health outcomes among offspring of affected women. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells

    PubMed Central

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has little effect on endoderm development from iPSCs, it reduces formation of hepatic progenitor cells during early hepatic specification. The proliferative activities of early and mature hepatocyte-like cells are significantly decreased after alcohol exposure. Importantly, at a mature stage of hepatocyte-like cells, alcohol treatment increases two liver progenitor subsets, causes oxidative mitochondrial injury and results in liver disease phenotypes (i.e., steatosis and hepatocellular carcinoma associated markers) in a dose dependent manner. Some of the phenotypes were significantly improved by antioxidant treatment. This report suggests that fetal alcohol exposure may impair generation of hepatic progenitors at early stage of hepatic specification and decrease proliferation of fetal hepatocytes; meanwhile alcohol injury in post-natal or mature stage human liver may contribute to disease phenotypes. This human iPSC model of alcohol-induced liver injury can be highly valuable for investigating alcoholic injury in the fetus as well as understanding the pathogenesis and ultimately developing effective treatment for alcoholic liver disease in adults. PMID:27570479

  4. Impairments in real-world executive function increase from childhood to adolescence in autism spectrum disorders.

    PubMed

    Rosenthal, Michael; Wallace, Gregory L; Lawson, Rachel; Wills, Meagan C; Dixon, Eunice; Yerys, Benjamin E; Kenworthy, Lauren

    2013-01-01

    Although several studies have investigated developmental trajectories of executive functioning (EF) in individuals with autism spectrum disorders (ASD) using lab-based tasks, no study to date has directly measured how EF skills in everyday settings vary at different ages. The current study seeks to extend prior work by evaluating age-related differences in parent-reported EF problems during childhood and adolescence in a large cross-sectional cohort of children with ASD. Children (N = 185) with an ASD without intellectual disability participated in the study. Participants were divided into four groups based on age (5-7, 8-10, 11-13, and 14-18-year-olds). The four age groups did not differ in IQ, sex ratio, or autism symptoms. There were significant age effects (i.e., worsening scores with increasing age) in three of G. A. Gioia, P. K. Isquith, S. Guy, and L. Kenworthy's (2000) BRIEF: Behavior Rating Inventory of Executive Function, Odessa, FL, Psychological Assessment Resources scale scores: Initiate (p = .007), working memory (p = .003), and organization of materials (p = .023). In addition, analysis of the BRIEF scale profile revealed that, although multiple scales were elevated, the shift scale showed the greatest problems in both the youngest and oldest age cohorts. Older children with ASD show greater EF problems compared with the normative sample than younger children with ASD. Specifically, there is a widening divergence from the normative sample in metacognitive executive abilities in children with ASD as they age. This, in combination with significant, albeit more stable, impairments in flexibility, has implications for the challenges faced by high-functioning individuals with ASD as they attempt to enter mainstream work and social environments.

  5. Increased oxytocin levels among abstinent heroin addicts: Association with aggressiveness, psychiatric symptoms and perceived childhood neglect.

    PubMed

    Gerra, Lidia M; Gerra, Gilberto; Mercolini, Laura; Manfredini, Matteo; Somaini, Lorenzo; Pieri, Chiara M; Antonioni, Maina; Protti, Michele; Ossola, Paolo; Marchesi, Carlo

    2017-04-03

    A disruption of the oxytocin system seems to affect a variety of brain functions including emotions, mood and social behavior possibly underlying severe social deficits and susceptibility for substance use and mental health disorders. Early life adversity, such as insecure attachment in childhood, has been suggested to influence oxytocin tone contributing to a condition of neurobiological vulnerability. Aim of the present study was to investigate oxytocin serum levels in abstinent heroin addicted patients, in comparison with healthy controls, and the possible correlation with co-occurring psychiatric symptoms, aggressiveness and perception of parental neglect. Eighteen (18) abstinent patients, affected by heroin use disorders, and 18 control subjects, who never used drugs or abused alcohol, were included in the study and submitted to 1) collection of a blood sample for oxytocin assay, 2) Symptoms Check List 90 for psychiatric symptoms evaluation 3) Buss Durkee Hostility Inventory to measure aggressiveness 4) Child Experience of Care and Abuse-Questionnaire to retrospectively test the perception of parental neglect. Heroin exposure extent and heroin dosages were also recorded. Oxytocin serum levels were unexpectedly significantly higher among abstinent patients affected by heroin use disorders and positively correlated with psychiatric symptoms, aggressiveness and mother neglect scores. No correlation was evidenced between oxytocin and heroin exposure extent or dosages. Our findings appear to contradict the simplistic view of oxytocin as a pro-social hormone and confirm previous evidence concerning the peptide levels direct association with aggressive behavior and mood disorders. Considering a more complex mechanism, oxytocin would increase the sensitivity to social salience cues related to contextual or inter-individual factors, promoting pro-sociality in "safe" conditions and, in contrast, inducing more defensive and "anti-social" emotions and behaviors when the

  6. Liver-specific Deficiency of Serine Palmitoyltransferase Subunit 2 Decreases Plasma Sphingomyelin and Increases Apolipoprotein E Levels*

    PubMed Central

    Li, Zhiqiang; Li, Yan; Chakraborty, Mahua; Fan, Yifan; Bui, Hai H.; Peake, David A.; Kuo, Ming-Shang; Xiao, Xiao; Cao, Guoqing; Jiang, Xian-Cheng

    2009-01-01

    Sphingomyelin (SM) is one of the major lipid components of plasma lipoproteins. Serine palmitoyltransferase (SPT) is the key enzyme in SM biosynthesis. Mice totally lacking in SPT are embryonic lethal. The liver is the major site for plasma lipoprotein biosynthesis, secretion, and degradation, and in this study we utilized a liver-specific knock-out approach for evaluating liver SPT activity and also its role in plasma SM and lipoprotein metabolism. We found that a deficiency of liver-specific Sptlc2 (a subunit of SPT) decreased liver SPT protein mass and activity by 95 and 92%, respectively, but had no effect on other tissues. Liver Sptlc2 deficiency decreased plasma SM levels (in both high density lipoprotein and non-high density lipoprotein fractions) by 36 and 35% (p < 0.01), respectively, and increased phosphatidylcholine levels by 19% (p < 0.05), thus increasing the phosphatidylcholine/SM ratio by 77% (p < 0.001), compared with controls. This deficiency also decreased SM levels in the liver by 38% (p < 0.01) and in the hepatocyte plasma membranes (based on a lysenin-mediated cell lysis assay). Liver-specific Sptlc2 deficiency significantly increased hepatocyte apoE secretion and thus increased plasma apoE levels 3.5-fold (p < 0.0001). Furthermore, plasma from Sptlc2 knock-out mice had a significantly stronger potential for promoting cholesterol efflux from macrophages than from wild-type mice (p < 0.01) because of a greater amount of apoE in the circulation. As a result of these findings, we believe that the ability to control liver SPT activity could result in regulation of lipoprotein metabolism and might have an impact on the development of atherosclerosis. PMID:19648608

  7. S-adenosylmethionine increases circulating very-low density lipoprotein clearance in nonalcoholic fatty liver disease

    PubMed Central

    Martinez-Una, Maite; Varela-Rey, Marta; Mestre, Daniela; Fernandez-Ares, Larraitz; Fresnedo, Olatz; Fernandez-Ramos, David; Juan, Virginia Gutierrez-de; Martin-Guerrero, Idoia; Garcia-Orad, Africa; Luka, Zigmund; Wagner, Conrad; Lu, Shelly C; Garcia-Monzon, Carmelo; Finnell, Richard H; Aurrekoetxea, Igor; Buque, Xabier; Martinez-Chantar, M. Luz; Mato, Jose M.; Aspichueta, Patricia

    2014-01-01

    Background Very-low density-lipoproteins (VLDL) export lipids from liver to peripheral tissues and are the precursors of low-density-lipoproteins. Low levels of hepatic S-adenosylmethionine (SAMe) decrease triglyceride (TG) secretion in VLDL contributing to hepatosteatosis in methionine adenosyltransferase 1A knockout mice but nothing is known about the effect of SAMe over circulating VLDL metabolism. Objective We wanted to investigate whether excess SAMe could disrupt VLDL plasma metabolism and unravel the mechanisms involved. Methods Glycine N-methyltransferase (GNMT) knockout (KO), GNMT-PLIN2-KO and their respective wild types (WT) were used. A high fat diet (HFD) or a methionine deficient diet (MDD) was administrated to exacerbate or recover VLDL metabolism, respectively. Finally, 33 patients with nonalcoholic fatty-liver disease (NAFLD); 11 with hypertriglyceridemia and 22 with normal lipidemia were used in this study. Results We found that excess SAMe increases turnover of hepatic TG stores for secretion in VLDL in GNMT-KO mice, a model of NAFLD with high SAMe levels. The disrupted VLDL assembly resulted in the secretion of enlarged, phosphatidylethanolamine-poor, TG-and apoE-enriched VLDL-particles; special features that lead to increased VLDL clearance and decreased serum TG levels. Re-establishing normal SAMe levels restore VLDL secretion, features and metabolism. In NAFLD patients, serum TG levels are lower when hepatic GNMT-protein expression is decreased. Conclusion Excess hepatic SAMe levels disrupt VLDL assembly and features and increase circulating VLDL clearance which will cause increased VLDL-lipid supply to tissues and might contribute to the extrahepatic complications of NAFLD. Electronic word count: 235 PMID:25457203

  8. Behavioral and neurophysiological evidence for increased cognitive flexibility in late childhood

    PubMed Central

    Wolff, Nicole; Roessner, Veit; Beste, Christian

    2016-01-01

    Executive functions, like the capacity to control and organize thoughts and behavior, develop from childhood to young adulthood. Although task switching and working memory processes are known to undergo strong developmental changes from childhood to adulthood, it is currently unknown how task switching processes are modulated between childhood and adulthood given that working memory processes are central to task switching. The aim of the current study is therefore to examine this question using a combined cue- and memory-based task switching paradigm in children (N = 25) and young adults (N = 25) in combination with neurophysiological (EEG) methods. We obtained an unexpected paradoxical effect suggesting that memory-based task switching is better in late childhood than in young adulthood. No group differences were observed in cue-based task switching. The neurophysiological data suggest that this effect is not due to altered attentional selection (P1, N1) or processes related to the updating, organization, and implementation of the new task-set (P3). Instead, alterations were found in the resolution of task-set conflict and the selection of an appropriate response (N2) when a task has to be switched. Our observation contrasts findings showing that cognitive control mechanisms reach their optimal functioning in early adulthood. PMID:27349808

  9. Strengthening Families in Illinois: Increasing Family Engagement in Early Childhood Programs

    ERIC Educational Resources Information Center

    Jor'dan, Jamilah R.; Wolf, Kathy Goetz; Douglass, Anne

    2012-01-01

    Strengthening Families is a relationship-based child abuse and neglect prevention initiative started nationally in 2001 through a partnership between the Doris Duke Charitable Foundation and the Center for the Study of Social Policy (CSSP) in Washington, DC. Thirty-five states and several thousand early childhood programs nationwide implement…

  10. Childhood neglect and increased withdrawal and depressive severity in crack cocaine users during early abstinence.

    PubMed

    Francke, Ingrid D'avila; Viola, Thiago Wendt; Tractenberg, Saulo Gantes; Grassi-Oliveira, Rodrigo

    2013-10-01

    Studies have shown that environmental factors, such as exposure to childhood maltreatment, might shift the course of addiction. Little is known, however, about whether childhood physical neglect (PN) influences the severity of withdrawal and depressive symptoms during the detoxification period. This is a 3 weeks follow-up study. The participants were divided into 2 groups: those with a history of PN (PN+) (n=32) and those without a history of PN (PN-) (n=48). Clinical variables were assessed with the SCID-I, BDI-II, Childhood Trauma Questionnaire, Addiction Severity Index and Cocaine Selective Severity Assessment. Depressive symptom assessments were repeated at three time points. Withdrawal symptom assessments were repeated at five different points following detoxification. A repeated measures analysis of covariance indicated that the PN+ group exhibited a significantly lower reduction in the severity of withdrawal symptoms compared to the PN- group (p<0.05). Post hoc analyses showed that after 12 days of treatment, the severity of withdrawal symptoms in the PN+ group did not decrease in the same level as was observed in the PN- group. Moreover, a strong correlation was found between the severity of depression and the intensity of the abstinence symptoms during treatment. Patients who reported more depressive symptoms also exhibited more severe withdrawal symptoms. The ASI-6 indicated higher severity problems related to alcohol and psychiatric disorders in the PN+ groups. Our data support the role of childhood PN in the contingencies of the detoxification process of crack cocaine-dependent women.

  11. Implementation of Music Activities to Increase Language Skills in the At-Risk Early Childhood Population

    ERIC Educational Resources Information Center

    Seeman, Elissa

    2008-01-01

    The purpose of this study was to examine the short-term effects of a music education intervention on the receptive language skills of students in an at-risk early childhood program. The target population was nine students ages 3, 4, and 5 in an at-risk, inclusive classroom in a Chicago public school. The problem of language delay is indicated in…

  12. Strengthening Families in Illinois: Increasing Family Engagement in Early Childhood Programs

    ERIC Educational Resources Information Center

    Jor'dan, Jamilah R.; Wolf, Kathy Goetz; Douglass, Anne

    2012-01-01

    Strengthening Families is a relationship-based child abuse and neglect prevention initiative started nationally in 2001 through a partnership between the Doris Duke Charitable Foundation and the Center for the Study of Social Policy (CSSP) in Washington, DC. Thirty-five states and several thousand early childhood programs nationwide implement…

  13. New Wine in Old Bottles: Increasing the Coherence of Early Childhood Care and Education Policy.

    ERIC Educational Resources Information Center

    Barnett, W. Steven

    1993-01-01

    Analyzes public interest in early childhood care and education (ECCE) policy. Chronicles federal policy in this area from the mid-1960s to the present, with particular attention to changes in the amount of funding and its allocation. Argues that ECCE policy is inadequately funded, fragmented, and internally inconsistent, and provides alternative…

  14. Qualities for Early Childhood Care and Education in an Age of Increasing Superdiversity and Decreasing Biodiversity

    ERIC Educational Resources Information Center

    Ritchie, Jenny

    2016-01-01

    In this article it is argued that notions of "quality" in early childhood education have been captured by neo-liberal discourses. These discourses perpetuate the western, individualistic, normativising and exploitative attitudes and practices that are contributing to the climate crisis currently imperilling our planet. Educators may…

  15. New Wine in Old Bottles: Increasing the Coherence of Early Childhood Care and Education Policy.

    ERIC Educational Resources Information Center

    Barnett, W. Steven

    1993-01-01

    Analyzes public interest in early childhood care and education (ECCE) policy. Chronicles federal policy in this area from the mid-1960s to the present, with particular attention to changes in the amount of funding and its allocation. Argues that ECCE policy is inadequately funded, fragmented, and internally inconsistent, and provides alternative…

  16. Effects of messages from a media campaign to increase public awareness of childhood obesity.

    PubMed

    Barry, Colleen L; Gollust, Sarah E; McGinty, Emma E; Niederdeppe, Jeff

    2014-02-01

    To examine how video messages from a recent media campaign affected public attitudes about obesity prevention and weight-based stigma toward obese children. A survey-embedded experiment in May-June 2012 with nationally representative sample (N = 1,677) was conducted. Participants were randomized to view one of three messages of children recounting struggles with obesity, or to a control group. It was examined whether message exposure affected attitudes about: (1) the seriousness of childhood obesity and its consequences; (2) responsibility for addressing obesity; (3) support for prevention policies, and (4) stigma toward obese children. Participants viewing the messages attributed greater responsibility for addressing childhood obesity to the food and beverage industry, schools, and the government, compared to those in the control group. Overweight and female respondents viewing the messages reported lower weight-based stigma compared with overweight and female respondents in the control group, but messages had no effect on healthy weight and male respondents. Messages did not affect attitudes about the seriousness of childhood obesity, its consequences, or support for obesity prevention policies. It will be critical to assess on an ongoing basis how communication campaigns addressing childhood obesity shape public attitudes about obesity prevention. Copyright © 2013 The Obesity Society.

  17. Impact of a Cultural Self-Analysis Project: Increasing Early Childhood Preservice Teachers' Cultural Competency

    ERIC Educational Resources Information Center

    Fuller, David P.; Miller, Kevin J.; Dominguez, Laura C.

    2006-01-01

    This study explored the impact of a Cultural Self-Analysis (CSA) Project on early childhood undergraduate preservice teachers' cultural awareness and dispositions toward working with culturally diverse students and families. The project was based on the ABC's of Cultural Understanding and Communication, a model designed to facilitate the…

  18. Increasing the Physical Educator's Impact: Consulting, Collaborating, and Teacher Training in Early Childhood Programs.

    ERIC Educational Resources Information Center

    Helm, Judy Harris; Boos, Suzi

    1996-01-01

    This article describes how an early childhood education center in Peoria, Illinois, used physical educators as ongoing consultants/collaborators to develop a structured movement curriculum. Five interactive workshops for teachers provided training in movement principles and skills; individual consultations; and information on developmentally…

  19. Qualities for Early Childhood Care and Education in an Age of Increasing Superdiversity and Decreasing Biodiversity

    ERIC Educational Resources Information Center

    Ritchie, Jenny

    2016-01-01

    In this article it is argued that notions of "quality" in early childhood education have been captured by neo-liberal discourses. These discourses perpetuate the western, individualistic, normativising and exploitative attitudes and practices that are contributing to the climate crisis currently imperilling our planet. Educators may…

  20. IL-10 and TGF-β unbalanced levels in neutrophils contribute to increase inflammatory cytokine expression in childhood obesity.

    PubMed

    Medeiros, Nayara I; Mattos, Rafael T; Menezes, Carlos A; Fares, Rafaelle C G; Talvani, André; Dutra, Walderez O; Rios-Santos, Fabrício; Correa-Oliveira, Rodrigo; Gomes, Juliana A S

    2017-07-22

    Obesity is a multifactorial disease, associated with metabolic disorders, chronic low-grade inflammation, and impaired immunity. This study aimed to evaluate the childhood obesity-associated effects on neutrophil activation and cytokine production. We evaluated activation and recognition markers and cytokine production in neutrophils from the peripheral blood of children with obesity and normal weight using multicolor flow cytometry. We demonstrate a higher frequency of neutrophils in childhood obesity group (CO) compared to normal-weight group (NW). Our data showed that neutrophils from CO group are capable of antigen recognition and presentation through higher expression of TLR-4 (CD284) and HLA-DR in comparison with neutrophils from NW. On the other hand, neutrophils from CO group are faulty to deliver co-stimulatory signals, through lower expression of co-stimulatory molecules. We showed an increased expression of IL-6, IL-1β, IL-12, and TNF, and decreased expression of IL-8 and IL-10 by neutrophils from CO compared to NW, while TGF-β is equivalently expressed in neutrophils from both groups. Despite this, we observed that TGF-β/inflammatory cytokine ratio was significantly higher than the IL-10/inflammatory cytokine ratio only in CO group. Our analysis showed obesity altering the correlation profile for the expression of co-stimulatory, recognition, and activation molecules, as well as for cytokines by neutrophils, suggesting an association between lower IL-10 expression and inflammation in childhood obesity. The unbalance between the ratio of IL-10 and TGF-β expressions, the IL-10 lower expression, and changes in correlation profile seem to contribute with an inefficient regulation of inflammatory cytokine expression in childhood obesity. However, these changes still not may be considered the sole mechanism that directs inflammation during childhood obesity, once other molecules, pathways, and cells should be evaluated.

  1. Increased activity of rat liver nucleolar protein kinase following triiodothyronine administration.

    PubMed

    Fugassa, E; Gallo, G; Pertica, M; Voci, A; Orunesu, M

    1977-12-08

    Triiodothyronine (T3) administration to thyroidectomized rats induces a significant increase in the nucleolus-associated protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) activity. The general properties of the protein kinase solubilized from liver nucleoli have been investigated. Mg2+ (20 mM) is essential for the reaction and an appropriate concentration of NaCl (100 mM) is required to achieve maximal phosphorylation rates. The optimal pH for casein phosphorylation is 7.6. The kinase phosphorylates casein more efficiently than phosvitin and displays an almost undetectable activity towards histones and protamine. No significant stimulation of the kinase activity by cyclic AMP has been detected. The apparent Km values for casein and ATP are 1.5 mg/ml and 1.5-10(-5) M, respectively, and are not affected by the hormone administration.

  2. Ischemic Preconditioning Increases the Tolerance of Fatty Liver to Hepatic Ischemia-Reperfusion Injury in the Rat

    PubMed Central

    Serafín, Anna; Roselló-Catafau, Joan; Prats, Neus; Xaus, Carme; Gelpí, Emilio; Peralta, Carmen

    2002-01-01

    Hepatic steatosis is a major risk factor in ischemia-reperfusion. The present study evaluates whether preconditioning, demonstrated to be effective in normal livers, could also confer protection in the presence of steatosis and investigates the potential underlying protective mechanisms. Fatty rats had increased hepatic injury and decreased survival after 60 minutes of ischemia compared with lean rats. Fatty livers showed a degree of neutrophil accumulation and microcirculatory alterations similar to that of normal livers. However, in presence of steatosis, an increased lipid peroxidation that could be reduced with glutathione-ester pretreatment was observed after hepatic reperfusion. Ischemic preconditioning reduced hepatic injury and increased animal survival. Both in normal and fatty livers, this endogenous protective mechanism was found to control lipid peroxidation, hepatic microcirculation failure, and neutrophil accumulation, reducing the subsequent hepatic injury. These beneficial effects could be mediated by nitric oxide, because the inhibition of nitric oxide synthesis and nitric oxide donor pretreatment abolished and simulated, respectively, the benefits of preconditioning. Thus, ischemic preconditioning could be an effective surgical strategy to reduce the hepatic ischemia-reperfusion injury in normal and fatty livers under normothermic conditions, including hepatic resections, and liver transplantation. PMID:12163383

  3. Increased hepatic CD36 expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease

    PubMed Central

    Sheedfar, Fareeba; Sung, Miranda MY; Aparicio-Vergara, Marcela; Kloosterhuis, Niels J; Miquilena-Colina, Maria Eugenia; Vargas-Castrillón, Javier; Febbraio, Maria; Jacobs, René L; de Bruin, Alain; Vinciguerra, Manlio; García-Monzón, Carmelo; Hofker, Marten H; Dyck, Jason RB; Koonen, Debby PY

    2014-01-01

    CD36 has been associated with obesity and diabetes in human liver diseases, however, its role in age-associated nonalcoholic fatty liver disease (NAFLD) is unknown. Therefore, liver biopsies were collected from individuals with histologically normal livers (n=30), and from patients diagnosed with simple steatosis (NAS; n=26). Patients were divided into two groups according to age and liver biopsy samples were immunostained for CD36. NAFLD parameters were examined in young (12-week) and middle-aged (52-week) C57BL/6J mice, some fed with chow-diet and some fed with low-fat (LFD; 10% kcal fat) or high-fat diet (HFD; 60% kcal fat) for 12-weeks. CD36 expression was positively associated with age in individuals with normal livers but not in NAS patients. However, CD36 was predominantly located at the plasma membrane of hepatocytes in aged NAS patients as compared to young. In chow-fed mice, aging, despite an increase in hepatic CD36 expression, was not associated with the development of NAFLD. However, middle-aged mice did exhibit the development of HFD-induced NAFLD, mediated by an increase of CD36 on the membrane. Enhanced CD36-mediated hepatic fat uptake may contribute to an accelerated progression of NAFLD in mice and humans. Therapies to prevent the increase in CD36 expression and/or CD36 from anchoring at the membrane may prevent the development of NAFLD. PMID:24751397

  4. Increased Glutathione Synthesis Following Nrf2 Activation by Vanadyl Sulfate in Human Chang Liver Cells

    PubMed Central

    Kim, Areum Daseul; Zhang, Rui; Kang, Kyoung Ah; You, Ho Jin; Hyun, Jin Won

    2011-01-01

    Jeju ground water, containing vanadium compounds, was shown to increase glutathione (GSH) levels as determined by a colorimetric assay and confocal microscopy. To investigate whether the effects of Jeju ground water on GSH were specifically mediated by vanadium compounds, human Chang liver cells were incubated for 10 passages in media containing deionized distilled water (DDW), Jeju ground water (S1 and S3), and vanadyl sulfate (VOSO4). Vanadyl sulfate scavenged superoxide anion, hydroxyl radical and intracellular reactive oxygen species. Vanadyl sulfate effectively increased cellular GSH level and up-regulated mRNA and protein expression of a catalytic subunit of glutamate cysteine ligase (GCLC), which is involved in GSH synthesis. The induction of GCLC expression by vanadyl sulfate was found to be mediated by transcription factor erythroid transcription factor NF-E2 (Nrf2), which critically regulates GCLC by binding to the antioxidant response elements (AREs). Vanadyl sulfate treatment increased the nuclear translocation of Nrf2 and the accumulation of phosphorylated Nrf2. Extracellular regulated kinase (ERK) contributed to ARE-driven GCLC expression via Nrf2 activation. Vanadyl sulfate induced the expression of the active phospho form of ERK. Taken together, these results suggest that the increase in GSH level by Jeju ground water is, at least in part, due to the effects of vanadyl sulfate via the Nrf2-mediated induction of GCLC. PMID:22272109

  5. An increase in liver PPARγ2 is an initial event to induce fatty liver in response to a diet high in butter: PPARγ2 knockdown improves fatty liver induced by high-saturated fat.

    PubMed

    Yamazaki, Tomomi; Shiraishi, Sayaka; Kishimoto, Kyoko; Miura, Shinji; Ezaki, Osamu

    2011-06-01

    The effects of a diet rich in saturated fat on fatty liver formation and the related mechanisms that induce fatty liver were examined. C57BL/6J mice were fed butter or safflower oil as a high-fat (HF) diet (40% fat calories) for 2, 4, 10, or 17 weeks. Although both HF diets induced similar levels of obesity, HF butter-fed mice showed a two to threefold increase in liver triacylglycerol (TG) concentration compared to HF safflower oil-fed mice at 4 or 10 weeks without hyperinsulinemia. At 4 weeks, increases in peroxisome proliferator-activated receptor γ2 (PPARγ2), CD36, and adipose differentiation-related protein (ADRP) mRNAs were observed in HF butter-fed mice; at 10 weeks, an increase in sterol regulatory element-binding protein-1c (SREBP-1c) was observed; at 17 weeks, these increases were attenuated. At 4 weeks, a single injection of adenoviral vector-based short hairpin interfering RNA against PPARγ2 in HF butter-fed mice reduced PPARγ protein and mRNA of its target genes (CD36 and ADRP) by 43%, 43%, and 39%, respectively, with a reduction in liver TG concentration by 38% in 5 days. PPARγ2 knockdown also reduced mRNAs in lipogenic genes (fatty-acid-synthase, stearoyl-CoA desaturase 1, acetyl-CoA carboxylase 1) without alteration of SREBP-1c mRNA. PPARγ2 knockdown reduced mRNAs in genes related to inflammation (CD68, interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein-1). In conclusion, saturated fatty acid-rich oil induced fatty liver in mice, and this was triggered initially by an increase in PPARγ2 protein in the liver, which led to increased expression of lipogenic genes. Inactivation of PPARγ2 may improve fatty liver induced by HF saturated fat.

  6. Apolipoprotein CIII Overexpression-Induced Hypertriglyceridemia Increases Nonalcoholic Fatty Liver Disease in Association with Inflammation and Cell Death

    PubMed Central

    Paiva, Adriene A.; Raposo, Helena F.; Wanschel, Amarylis C. B. A.; Nardelli, Tarlliza R.

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the principal manifestation of liver disease in obesity and metabolic syndrome. By comparing hypertriglyceridemic transgenic mice expressing apolipoprotein (apo) CIII with control nontransgenic (NTg) littermates, we demonstrated that overexpression of apoCIII, independent of a high-fat diet (HFD), produces NAFLD-like features, including increased liver lipid content; decreased antioxidant power; increased expression of TNFα, TNFα receptor, cleaved caspase-1, and interleukin-1β; decreased expression of adiponectin receptor-2; and increased cell death. This phenotype is aggravated and additional NAFLD features are differentially induced in apoCIII mice fed a HFD. HFD induced glucose intolerance together with increased gluconeogenesis, indicating hepatic insulin resistance. Additionally, the HFD led to marked increases in plasma TNFα (8-fold) and IL-6 (60%) in apoCIII mice. Cell death signaling (Bax/Bcl2), effector (caspase-3), and apoptosis were augmented in apoCIII mice regardless of whether a HFD or a low-fat diet was provided. Fenofibrate treatment reversed several of the effects associated with diet and apoCIII expression but did not normalize inflammatory traits even when liver lipid content was fully corrected. These results indicate that apoCIII and/or hypertriglyceridemia plays a major role in liver inflammation and cell death, which in turn increases susceptibility to and the severity of diet-induced NAFLD. PMID:28163820

  7. Increased Risk of Smoking in Female Adolescents Who Had Childhood ADHD.

    PubMed

    Elkins, Irene J; Saunders, Gretchen R B; Malone, Stephen M; Keyes, Margaret A; Samek, Diana R; McGue, Matt; Iacono, William G

    2017-08-25

    This study examined the effects of childhood attention deficit hyperactivity disorder (ADHD) symptoms, both inattention and hyperactivity-impulsivity, on the development of smoking in male and female adolescents. Twin difference methods were used to control for shared genetic and environmental confounders in three population-based, same-sex twin samples (N=3,762; 64% monozygotic). One cohort oversampled female adolescents with ADHD beginning in childhood. Regressions of childhood inattentive and hyperactive-impulsive symptoms were conducted to predict smoking outcomes by age 17. ADHD effects were divided into those shared between twins in the pair and those nonshared, or different within pairs. Adolescents who had more severe ADHD symptoms as children were more likely to initiate smoking and to start smoking younger. The association of ADHD symptoms with daily smoking, number of cigarettes per day, and nicotine dependence was greater in females than in males. Monozygotic female twins with greater attentional problems than their co-twins had greater nicotine involvement, consistent with possible causal influence. These effects remained when co-occurring externalizing behaviors and stimulant medication were considered. Hyperactivity-impulsivity, while also more strongly related to smoking for female adolescents, appeared primarily noncausal. Smoking initiation and escalation are affected differentially by ADHD subtype and gender. The association of inattention with smoking in female adolescents may be causal, whereas hyperactivity-impulsivity appears to act indirectly, through shared propensities for both ADHD and smoking.

  8. The model for end-stage liver disease allocation system for liver transplantation saves lives, but increases morbidity and cost: a prospective outcome analysis.

    PubMed

    Dutkowski, Philipp; Oberkofler, Christian E; Béchir, Markus; Müllhaupt, Beat; Geier, Andreas; Raptis, Dimitri A; Clavien, Pierre-Alain

    2011-06-01

    We analyzed the first 100 patients who underwent liver transplantation by Model for End-Stage Liver Disease (MELD) allocation, and compared the outcome of patients on the waiting list and after orthotopic liver transplantation with the last 100 patients who underwent transplantation prior to the introduction of the MELD system in July 2007. MELD allocation resulted in decreased waiting list mortality (386 versus 242 deaths per 1000 patient-years, P < 0.0001) and the transplantation of sicker recipients (uncorrected median MELD score 13.5 versus 20, P = 0.003). Recipient posttransplant morbidity was significantly higher, mainly caused by increased percentage of renal failure requiring renal replacement therapy (13 versus 46%, P < 0.0001). However, kidney function recovered in most cases within 6 months after OLT. Hospital mortality remained similar in both groups (6% versus 9%). Patient 1-year survival was 91% versus 83% (pre-MELD versus MELD era, P = 0.2154), graft 1-year survival was 88% versus 78% (P = 0.1013), respectively. Costs accumulated were significantly higher after introduction of the MELD policy (US $81,967 versus US $127,453, a 55% increase, P = 0.02) with a strong correlation with the individual MELD score (P < 0.0001). The MELD system addresses the goal of fairness well. However, the postoperative course appears more difficult in the MELD era with increased financial burden, but reasonable patient and graft survival. This is the inevitable price to balance justice and utility in liver graft allocation. Copyright © 2011 American Association for the Study of Liver Diseases.

  9. Stunted growth, increased mortality, and liver tumors in offspring of polybrominated biphenyl (PBB) dosed sherman rats.

    PubMed

    Groce, D F; Kimbrough, R D

    1984-01-01

    Firemaster FF-1, a polybrominated biphenyl (PBB) mixture, was dissolved in corn oil and given as a dose of 200 mg/kg body weight to Sherman rats on d 7 and 14 of pregnancy. Control rats received equivalent doses of corn oil alone. Selected pups and all dams were killed 1 mo after pups were weaned. A total of 50 male and 50 female offspring per group were followed until they were 2 yr old. The livers of offspring killed at the ages of 2 mo and 2 yr had PBB levels of 2,4 (SD 1.2) and 0.8 (SD 0.65) mg/kg for females and 3.0 (SD 1.6) and 0.6 (SD 0.37) mg/kg for males, respectively. The incidence of hepatocellular carcinomas was 3/51 (5.9%) and 4/41 (9.6%) after 2 yr in females and males, respectively. Hepatocellular carcinomas were not observed among the controls. Neoplastic (hyperplastic) nodules of the liver were present in 9/51 (17.6%) and 2/41 (4.9%) of exposed females and males, respectively, whereas only 2/48 (4.2%) of control females and no control males had neoplastic (hyperplastic) nodules. Body weights were lower in PBB-exposed rats at ages 1, 6, 12, and 24 mo. Survival rates from birth to weaning were lower in PBB-exposed pups (89%) than in controls (98%). Mortality was two times higher in PBB-exposed males (64%) than in control males (32%) after 2 yr. Transplacental PBB exposure and exposure through milk resulted in PBB body burdens in the offspring still measurable at the end of their lifespan. These offspring had increased mortality rates and lower body weights than controls, and they developed hepatocellular carcinomas.

  10. Lactulose increases equol production and improves liver antioxidant status in barrows treated with Daidzein.

    PubMed

    Zheng, Weijiang; Hou, Yanjun; Yao, Wen

    2014-01-01

    Equol, one of the intestinal microflora metabolites of daidzein, has gained much attention for having greater bioactivity than its precursor (daidzein and daidzin) and seeming to be promoted by hydrogen gas. The effects of lactulose on the equol-producing capacity and liver antioxidant status of barrows treated with daidzein were investigated in this study. Male castrated piglets (barrows) of Landrace × Duroc, aged 40 days, were randomly divided into the following three groups: control group (C, n = 12, fed an isoflavones-free basic diet), daidzein group (D, n = 12, fed an isoflavones-free basic diet with 50 mg/kg of daidzein supplementation) and daidzein+lactulose group (D+L, n = 12, fed an isoflavones-free basic diet with 1% of lactulose and 50 mg/kg of daidzein supplementation). After 20 days, the profile of short-chain fatty acids in the colon digesta showed that lactulose significantly increased the fermented capacity in the gastrointestinal tract of the barrows. First-void urinary equol concentrations were significantly higher in the D+L group than in the D group (3.13 ± 0.93 compared to 2.11 ± 0.82 μg/ml, respectively). Furthermore, fecal equol levels were also significantly higher in the D+L group than in the D group (12.00 ± 2.68 compared to 10.00 ± 2.26 μg/g, respectively). The population of bacteroidetes and the percentage of bacteroidetes to bacteria in feces were higher in the D+L group than in the D group. The DGGE profiles results indicate that lactulose might shift the pathways of hydrogen utilization, and changing the profiles of SRB in feces. Moreover, the D+L group had weak enhancement of T-SOD and CuZn-SOD activities in the livers of barrows treated with daidzein.

  11. Lactulose Increases Equol Production and Improves Liver Antioxidant Status in Barrows Treated with Daidzein

    PubMed Central

    Zheng, Weijiang; Hou, Yanjun; Yao, Wen

    2014-01-01

    Equol, one of the intestinal microflora metabolites of daidzein, has gained much attention for having greater bioactivity than its precursor (daidzein and daidzin) and seeming to be promoted by hydrogen gas. The effects of lactulose on the equol-producing capacity and liver antioxidant status of barrows treated with daidzein were investigated in this study. Male castrated piglets (barrows) of Landrace×Duroc, aged 40 days, were randomly divided into the following three groups: control group (C, n = 12, fed an isoflavones-free basic diet), daidzein group (D, n = 12, fed an isoflavones-free basic diet with 50 mg/kg of daidzein supplementation) and daidzein+lactulose group (D+L, n = 12, fed an isoflavones-free basic diet with 1% of lactulose and 50 mg/kg of daidzein supplementation). After 20 days, the profile of short-chain fatty acids in the colon digesta showed that lactulose significantly increased the fermented capacity in the gastrointestinal tract of the barrows. First-void urinary equol concentrations were significantly higher in the D+L group than in the D group (3.13±0.93 compared to 2.11±0.82 μg/ml, respectively). Furthermore, fecal equol levels were also significantly higher in the D+L group than in the D group (12.00±2.68 compared to 10.00±2.26 μg/g, respectively). The population of bacteroidetes and the percentage of bacteroidetes to bacteria in feces were higher in the D+L group than in the D group. The DGGE profiles results indicate that lactulose might shift the pathways of hydrogen utilization, and changing the profiles of SRB in feces. Moreover, the D+L group had weak enhancement of T-SOD and CuZn-SOD activities in the livers of barrows treated with daidzein. PMID:24667812

  12. Increase in the prevalence of arthritis in adulthood among adults exposed to Chinese famine of 1959 to 1961 during childhood

    PubMed Central

    Xu, Xianglong; Liu, Lingli; Xie, Wenxi; Zhang, Yong; Zeng, Huan; Zhang, Fan; Reis, Cesar; Cao, Xianqing; Zhao, Yong

    2017-01-01

    Abstract The developmental origins hypothesis postulates that under-nutrition in the early stage of life is associated with an increased risk of disease in adulthood. This study aimed to examine the association of exposure to the Chinese famine of 1959 to 1961 in early life with the risk of arthritis in adulthood. From July to September 2009, the study adopted multistage stratified random sampling cross-sectional survey to recruit 1224 eligible adults in Chongqing. Famine exposure groups were categorized into 3 groups: (1) childhood exposure, (2) fetal exposure, and (3) nonexposure. Self-reported arthritis of physician diagnosis was obtained. A total of 1224 eligible respondents were interviewed, including 299 individuals exposed during childhood, 455 exposed when fetal, and 470 without exposure. The prevalence of arthritis in adulthood among individuals exposed to famine during childhood was significantly higher than those not exposed (17.39% vs 11.28%, odds ratio [OR] = 1.573 with a 95% confidence interval of [CI] [1.020, 2.424]). Persons exposed to famine during the fetal period did not significantly contribute to a higher rate of arthritis in adulthood than those who were not exposed to famine (13.19% vs 11.28%, OR = 1.072, 95% CI = 0.713, 1.613). In addition, education level, the average monthly income, sleep status, and satisfaction of the present living condition were associated with the risk of arthritis in adulthood. Exposure to the Chinese famine during childhood may be associated with an increased risk of arthritis in adulthood. This study suggests that early life nutrition may have an effect on the risk of arthritis in adulthood. PMID:28353598

  13. Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India

    PubMed Central

    2012-01-01

    Background Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population. Methods Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. Results Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased in the arsenic exposed group. Conclusions Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk. PMID:22883023

  14. Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India.

    PubMed

    Das, Nandana; Paul, Somnath; Chatterjee, Debmita; Banerjee, Nilanjana; Majumder, Niladri S; Sarma, Nilendu; Sau, Tanmoy J; Basu, Santanu; Banerjee, Saptarshi; Majumder, Papiya; Bandyopadhyay, Apurba K; States, J Christopher; Giri, Ashok K

    2012-08-10

    Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population. Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased in the arsenic exposed group. Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk.

  15. Portal vein omentin is increased in patients with liver cirrhosis but is not associated with complications of portal hypertension.

    PubMed

    Eisinger, Kristina; Krautbauer, Sabrina; Wiest, Reiner; Karrasch, Thomas; Hader, Yvonne; Scherer, Marcus N; Farkas, Stefan; Aslanidis, Charalampos; Buechler, Christa

    2013-09-01

    Omentin is a visceral fat-derived adipokine associated with endothelium-dependent vasodilation. Impaired endothelial function is a major cause of portal hypertension in liver cirrhosis. The aim was to assess associations of omentin with systemic markers of endothelial function, namely arginine and asymmetric dimethylarginine (ADMA) and complications of portal hypertension in liver cirrhosis. Systemic omentin was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS) and hepatic venous serum (HVS) of 40 patients with liver cirrhosis and 10 liver-healthy controls. ADMA and arginine were determined in SVS of the patients by ELISA. Omentin is elevated in PVS and tends to be increased in SVS and HVS of patients with liver cirrhosis compared with controls. Omentin is principally expressed in visceral fat, and PVS omentin tends to be higher than SVS levels. Lower HVS than PVS omentin suggests that omentin may be partly removed from the circulation by the liver. Omentin in serum is not associated with stages of liver cirrhosis defined by CHILD-POUGH or MELD score and is not affected in patients with ascites. HVS omentin tends to be reduced in patients with large varices compared with patients without/with small varices. Arginine/ADMA ratio is reduced in patients with massive ascites but is not associated with variceal size. Further, Arginine/ADMA ratio does not correlate with omentin. Current data show that PVS omentin is increased in liver cirrhosis but is not associated with complications of portal hypertension. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  16. Hepatic insulin signaling changes: possible mechanism in prenatal hypoxia-increased susceptibility of fatty liver in adulthood.

    PubMed

    Cao, Li; Mao, Caiping; Li, Shigang; Zhang, Yujuan; Lv, Juanxiu; Jiang, Shan; Xu, Zhice

    2012-10-01

    Nonalcoholic fatty liver disease (NAFLD) is strongly linked to insulin resistance. Prenatal hypoxia (PH) is a risk factor in programming of insulin resistance, glucose intolerance, and metabolic dysfunctions in later life, although the mechanisms are unclear. In this study, the role of metabolic and histological changes as well as the hepatic insulin signaling mechanisms were determined in increasing susceptibility of NAFLD in the fetus and offspring exposed to PH. Pregnant rats exposed to hypoxia (O(2) 10%) during pregnancy demonstrated decreased fetal body and liver weight as well as liver to body weight ratio, whereas these changes were not observed in the offspring. However, male liver to body weight ratio increased after PH stress. Microscopic analysis demonstrated that exposure to PH resulted in distorted architecture of the hepatic parenchyma cells with reduced cellularity in the fetus and offspring. Blood glucose and insulin levels were lower with enhanced insulin sensitivity and increased expression of hepatic insulin-signaling elements in the fetus. Furthermore, insulin resistance, impaired glucose homeostasis, and altered expression of insulin-signaling elements occurred in the offspring. Postnatal hypoxia increased hepatic lipid droplets and triglyceride in liver, whereas expressions of insulin-signaling elements were less in the offspring exposed to PH except glucose transporters 2. The results indicated that PH contributed to hepatocyte heteroplasia and metabolic changes that enhanced vulnerability for NAFLD in the offspring, probably via affecting insulin signaling pathway, including glucose transporters 2.

  17. Reproduction Does Not Adversely Affect Liver Mitochondrial Respiratory Function but Results in Lipid Peroxidation and Increased Antioxidants in House Mice.

    PubMed

    Mowry, Annelise V; Kavazis, Andreas N; Sirman, Aubrey E; Potts, Wayne K; Hood, Wendy R

    2016-01-01

    Reproduction is thought to come at a cost to longevity. Based on the assumption that increased energy expenditure during reproduction is associated with increased free-radical production by mitochondria, oxidative damage has been suggested to drive this trade-off. We examined the impact of reproduction on liver mitochondrial function by utilizing post-reproductive and non-reproductive house mice (Mus musculus) living under semi-natural conditions. The age-matched post-reproductive and non-reproductive groups were compared after the reproductive females returned to a non-reproductive state, so that both groups were in the same physiological state at the time the liver was collected. Despite increased oxidative damage (p = 0.05) and elevated CuZnSOD (p = 0.002) and catalase (p = 0.04) protein levels, reproduction had no negative impacts on the respiratory function of liver mitochondria. Specifically, in a post-reproductive, maintenance state the mitochondrial coupling (i.e., respiratory control ratio) of mouse livers show no negative impacts of reproduction. In fact, there was a trend (p = 0.059) to suggest increased maximal oxygen consumption by liver mitochondria during the ADP stimulated state (i.e., state 3) in post-reproduction. These findings suggest that oxidative damage may not impair mitochondrial respiratory function and question the role of mitochondria in the trade-off between reproduction and longevity. In addition, the findings highlight the importance of quantifying the respiratory function of mitochondria in addition to measuring oxidative damage.

  18. Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.

    PubMed

    Fok, Wilson C; Chen, Yidong; Bokov, Alex; Zhang, Yiqiang; Salmon, Adam B; Diaz, Vivian; Javors, Martin; Wood, William H; Zhang, Yongqing; Becker, Kevin G; Pérez, Viviana I; Richardson, Arlan

    2014-01-01

    Rapamycin was found to increase (11% to 16%) the lifespan of male and female C57BL/6J mice most likely by reducing the increase in the hazard for mortality (i.e., the rate of aging) term in the Gompertz mortality analysis. To identify the pathways that could be responsible for rapamycin's longevity effect, we analyzed the transcriptome of liver from 25-month-old male and female mice fed rapamycin starting at 4 months of age. Few changes (<300 transcripts) were observed in transcriptome of rapamycin-fed males; however, a large number of transcripts (>4,500) changed significantly in females. Using multidimensional scaling and heatmap analyses, the male mice fed rapamycin were found to segregate into two groups: one group that is almost identical to control males (Rapa-1) and a second group (Rapa-2) that shows a change in gene expression (>4,000 transcripts) with more than 60% of the genes shared with female mice fed Rapa. Using ingenuity pathway analysis, 13 pathways were significantly altered in both Rapa-2 males and rapamycin-fed females with mitochondrial function as the most significantly changed pathway. Our findings show that rapamycin has a major effect on the transcriptome and point to several pathways that would likely impact the longevity.

  19. Mice Fed Rapamycin Have an Increase in Lifespan Associated with Major Changes in the Liver Transcriptome

    PubMed Central

    Fok, Wilson C.; Chen, Yidong; Bokov, Alex; Zhang, Yiqiang; Salmon, Adam B.; Diaz, Vivian; Javors, Martin; Wood, William H.; Zhang, Yongqing; Becker, Kevin G.; Pérez, Viviana I.; Richardson, Arlan

    2014-01-01

    Rapamycin was found to increase (11% to 16%) the lifespan of male and female C57BL/6J mice most likely by reducing the increase in the hazard for mortality (i.e., the rate of aging) term in the Gompertz mortality analysis. To identify the pathways that could be responsible for rapamycin's longevity effect, we analyzed the transcriptome of liver from 25-month-old male and female mice fed rapamycin starting at 4 months of age. Few changes (<300 transcripts) were observed in transcriptome of rapamycin-fed males; however, a large number of transcripts (>4,500) changed significantly in females. Using multidimensional scaling and heatmap analyses, the male mice fed rapamycin were found to segregate into two groups: one group that is almost identical to control males (Rapa-1) and a second group (Rapa-2) that shows a change in gene expression (>4,000 transcripts) with more than 60% of the genes shared with female mice fed Rapa. Using ingenuity pathway analysis, 13 pathways were significantly altered in both Rapa-2 males and rapamycin-fed females with mitochondrial function as the most significantly changed pathway. Our findings show that rapamycin has a major effect on the transcriptome and point to several pathways that would likely impact the longevity. PMID:24409289

  20. Obesity portends increased morbidity and earlier recurrence following liver transplantation for hepatocellular carcinoma.

    PubMed

    Mathur, Abhishek; Franco, Edson S; Leone, John P; Osman-Mohamed, Hussein; Rojas, Haydy; Kemmer, Nyingi; Neff, Guy W; Rosemurgy, Alexander S; Alsina, Angel E

    2013-07-01

    Obesity has been associated with poor oncologic outcomes following pancreatoduodenectomy for pancreatic cancer. However, there is a paucity of evidence on the impact of obesity on postoperative complications, oncologic outcome and survival in patients with hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT). From a database of over 1000 patients who underwent OLT during 1996-2008, 159 patients with a diagnosis of HCC were identified. Demographic data, body mass index (BMI), perioperative parameters, recurrence and survival were obtained. Complications were grouped according to Clavien-Dindo grading (Grades I-V). There were increased incidences of life-threatening complications in overweight (58%) and obese (70%) patients compared with the non-obese patient group (41%) (P < 0.05). Furthermore, the incidence of recurrence of HCC was doubled in the presence of overweight (15%) and obesity (15%) compared with non-obesity (7%) (P < 0.05). Time to recurrence also decreased significantly. Differences in mean ± standard deviation survival in the overweight (45 ± 3 months) and obese (41 ± 4 months) groups compared with the non-obese group (58 ± 6 months) did not reach statistical significance. These findings indicate that BMI is an important surrogate marker for obesity and portends an increased risk for complications and a poorer oncologic outcome following OLT for HCC. © 2012 International Hepato-Pancreato-Biliary Association.

  1. Early-life indoor environmental exposures increase the risk of childhood asthma.

    PubMed

    Chen, Yang-Ching; Tsai, Ching-Hui; Lee, Yungling Leo

    2011-12-01

    We aim to explore the relationships between exposure to dampness, pets, and environmental tobacco smoke (ETS) early in life and asthma in Taiwanese children, and to discuss their links to early- and late-onset asthma. We conducted a 1:2 matched case-control study from the Taiwan Children Health Study, which was a nationwide study that recruited 12-to-14 year-old school children in 14 communities. The 579 mothers of the participants were interviewed by telephone about their children's environmental exposures before they were 5 years old, including the in-utero period. Childhood asthma was associated with exposure to early life environmental factors, such as cockroaches (OR=2.16; 95% CI, 1.15-4.07), visible mould (OR=1.75; 95% CI, 1.15-2.67), mildewy odors (OR=5.04; 95% CI, 2.42-10.50), carpet (OR=2.36; 95% CI, 1.38-4.05), pets (OR=2.11; 95% CI, 1.20-3.72), and more than one hour of ETS per day (OR=1.93; 95% CI, 1.16-3.23). The ORs for mildewy odors, feather pillows, and ETS during early childhood were greater among children with late-onset asthma. Cockroaches, carpet, pets, and in-utero exposures to ETS affected the timing of early-onset asthma. Exposure to these factors led to dose-responsiveness in the risk of asthma. And the earlier exposures may trigger the earlier onset. Interventions in avoiding these environmental exposures are necessary for early-prevention of childhood asthma.

  2. Increased sensitivity of the European medicines agency algorithm for classification of childhood granulomatosis with polyangiitis.

    PubMed

    Uribe, América G; Huber, Adam M; Kim, Susan; O'Neil, Kathleen M; Wahezi, Dawn M; Abramson, Leslie; Baszis, Kevin; Benseler, Susanne M; Bowyer, Suzanne L; Campillo, Sarah; Chira, Peter; Hersh, Aimee O; Higgins, Gloria C; Eberhard, Anne; Ede, Kaleo; Imundo, Lisa F; Jung, Lawrence; Kingsbury, Daniel J; Klein-Gitelman, Marisa; Lawson, Erica F; Li, Suzanne C; Lovell, Daniel J; Mason, Thomas; McCurdy, Deborah; Muscal, Eyal; Nassi, Lorien; Rabinovich, Egla; Reiff, Andreas; Rosenkranz, Margalit; Schikler, Kenneth N; Singer, Nora G; Spalding, Steven; Stevens, Anne M; Cabral, David A

    2012-08-01

    Granulomatosis with polyangiitis (Wegener's; GPA) and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare in childhood and are sometimes difficult to discriminate. We compared use of adult-derived classification schemes for GPA against validated pediatric criteria in the ARChiVe (A Registry for Childhood Vasculitis e-entry) cohort, a Childhood Arthritis and Rheumatology Research Alliance initiative. Time-of-diagnosis data for children with physician (MD) diagnosis of AAV and unclassified vasculitis (UCV) from 33 US/Canadian centers were analyzed. The European Medicines Agency (EMA) classification algorithm and European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) and American College of Rheumatology (ACR) criteria for GPA were applied to all patients. Sensitivity and specificity were calculated (MD-diagnosis as reference). MD-diagnoses for 155 children were 100 GPA, 25 microscopic polyangiitis (MPA), 6 ANCA-positive pauciimmune glomerulonephritis, 3 Churg-Strauss syndrome, and 21 UCV. Of these, 114 had GPA as defined by EMA, 98 by EULAR/PRINTO/PRES, and 87 by ACR. Fourteen patients were identified as GPA by EULAR/PRINTO/PRES but not by ACR; 3 were identified as GPA by ACR but not EULAR/PRINTO/PRES. Using the EMA algorithm, 135 (87%) children were classifiable. The sensitivity of the EMA algorithm, the EULAR/PRINTO/PRES, and ACR criteria for classifying GPA was 90%, 77%, and 69%, respectively, with specificities of 56%, 62%, and 67%. The relatively poor sensitivity of the 2 criteria related to their inability to discriminate patients with MPA. EULAR/PRINTO/PRES was more sensitive than ACR criteria in classifying pediatric GPA. Neither classification system has criteria for MPA; therefore usefulness in discriminating patients in ARChiVe was limited. Even when using the most sensitive EMA algorithm, many children remained unclassified.

  3. Head and neck irradiation in childhood: increased risk of developing thyroid disease

    SciTech Connect

    Sako, K. )

    1991-03-01

    A nodule of the thyroid in a patient with a history of prior irradiation to the head and neck area in childhood is more likely to be malignant than a nodule in the general population. Thirty-two of 144 such patients (22%) who came to surgery were found to have a carcinoma of the thyroid. A relative short-term (6 mo) trial with suppressive therapy with a thyroactive agent may be helpful in selecting out those nodules that may be malignant. Although considerable controversy continues to exist as to the proper surgical treatment, our current surgical management involves performing a total extracapsular thyroidectomy.11 references.

  4. Increased soluble CD36 is linked to advanced steatosis in nonalcoholic fatty liver disease.

    PubMed

    García-Monzón, Carmelo; Lo Iacono, Oreste; Crespo, Javier; Romero-Gómez, Manuel; García-Samaniego, Javier; Fernández-Bermejo, Miguel; Domínguez-Díez, Agustín; Rodríguez de Cía, Javier; Sáez, Alicia; Porrero, José Luís; Vargas-Castrillón, Javier; Chávez-Jiménez, Enrique; Soto-Fernández, Susana; Díaz, Ainhoa; Gallego-Durán, Rocío; Madejón, Antonio; Miquilena-Colina, María Eugenia

    2014-01-01

    Soluble CD36 (sCD36) clusters with insulin resistance, but no evidence exists on its relationship with hepatic fat content. We determined sCD36 to assess its link to steatosis in nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) patients. Two hundred and twenty-seven NAFLD, eighty-seven CHC, and eighty-five patients with histologically normal liver (NL) were studied. Steatosis was graded by Kleiner's histological scoring system. Serum sCD36 and hepatic CD36 expression was assessed by immunoassay and immunohistochemistry, respectively. In NAFLD, serum sCD36 levels were significantly higher in simple steatosis than in NL (361.4 ± 286.4 vs. 173.9 ± 137.4 pg/mL, respectively; P < 0.001), but not in steatohepatitis (229.6 ± 202.5 pg/mL; P = 0.153). In CHC, serum sCD36 levels were similar regardless of the absence (428.7 ± 260.3 pg/mL) or presence of steatosis (387.2 ± 283.6 pg/mL; P = 0.173). A progressive increase in serum sCD36 values was found in NAFLD depending on the histological grade of steatosis (P < 0.001), but not in CHC (P = 0.151). Serum sCD36 concentrations were independently associated with advanced steatosis in NAFLD when adjusted by demographic and anthropometric features [odds ratio (OR), 1.001; 95% confidence interval (CI), 1.000 to 1.002; P = 0.021] and by metabolic variables (OR, 1.002; 95% CI, 1.000 to 1.003; P = 0.001). Interestingly, a significant correlation was observed between hepatic CD36 and serum sCD36 (ρ = 0.499, P < 0.001). Increased serum sCD36 is an independent factor associated with advanced steatosis in NAFLD. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  5. ALKALINE RIBONUCLEASE ACTIVITY INCREASE IN RAT KIDNEY CORTEX AND LIVER AFTER TRYPAN BLUE AND OTHER AZO DYES ADMINISTRATION

    PubMed Central

    Rabinovitch, M.; Brentani, R.; Ferreira, S.; Fausto, N.; Maack, T.

    1961-01-01

    Acid azo dyes, most of them naphtholdisulfonic acid derivatives, were given intraperitoneally to rats and their effect on "alkaline" ribonuclease activity was studied in total homogenates of kidney cortex and liver. Acid treatment was used to release bound enzyme activity. Several of the dyes, including trypan blue, increased RNase activity in both organs 3 days after administration of single doses, while others, like Evans blue, were inactive. Activity was apparently bound to the sulfonic substitution in the 3, 6 positions in the naphthalene rings, substitutions in the benzidine rings being not critical. All of the active and most of the inactive compounds were taken up by tubule cells of kidney cortex and by reticular and parenchymal cells of liver. While the effect on both liver and kidney was obtained 1 day after trypan blue administration, RNase remained increased for only about 3 days in the first organ, and for at least a month in the second. However, repeated trypan blue doses increased liver enzyme activity for at least 9 days. Serum RNase activity was decreased after trypan blue administration. Ethionine administration together with trypan blue markedly blocked the effect of the dye on liver RNase activity; simultaneously given methionine partially reversed the action of the antimetabolite. This suggests that de novo synthesis of RNase is induced in liver by trypan blue. The action of ethionine on the kidney RNase response to trypan blue was less marked although significant; in view of the possible kidney uptake of the plasma enzyme, interpretation of this finding must be postponed. Results are discussed with reference to the mechanism of the structural specificity of the compounds used, cytological localization of the dyes and their mechanism of action on liver and kidney RNase. PMID:13738846

  6. Increased blood-brain transfer in a rabbit model of acute liver failure

    SciTech Connect

    Horowitz, M.E.; Schafer, D.F.; Molnar, P.; Jones, E.A.; Blasberg, R.G.; Patlak, C.S.; Waggoner, J.; Fenstermacher, J.D.

    1983-05-01

    The blood-to-brain transfer of (/sup 14/C)alpha-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine. The blood-to-brain transfer of alpha-aminoisobutyric acid was similar in control animals and animals 2 and 7 h after galactosamine injections, but was increased five- to tenfold in certain gray-matter areas of the brain in animals 11 and 18 h after galactosamine treatment. No detectable differences in white-matter uptake of (/sup 14/C)alpha-aminoisobutyric acid were found between the control and treated groups. The increase in alpha-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas. No clinical signs of early hepatic encephalopathy were observed in the treated rabbits, except for 1 animal from the 18-h postgalactosamine group. Thus, enhanced blood-brain transfer of alpha-aminoisobutyric acid preceded the development of overt hepatic encephalopathy. The distribution of radioactivity after the intravenous administration of (/sup 14/C)galactosamine showed that virtually none of the hepatotoxin localized in the brain, suggesting that the drug itself does not have a direct effect upon the blood-brain barrier or the brain. The increased uptake of alpha-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy.

  7. Fasting increases the concentrations of carbon tetrachloride and of its metabolite chloroform in the liver of mice.

    PubMed

    Pentz, R; Strubelt, O

    1983-05-01

    Fasting mice for 24 h strongly enhanced hepatic triglyceride concentrations as well as the hepatic levels of carbon tetrachloride (CCl4) and chloroform (CHCl3) after i.p. injection of 0.1 ml/kg CCl4. The ratio CHCl3:CCl4 was lower in the livers of the fasted than in those of the fed mice. Fasting-induced steatosis leading to an increased affinity of the liver to a lipophilic compound like CCl4 is considered to be the cause for the increase in CCl4 hepatotoxicity induced by fasting in mice.

  8. Simvastatin increases liver branched-chain α-ketoacid dehydrogenase activity in rats fed with low protein diet.

    PubMed

    Knapik-Czajka, Malgorzata

    2014-11-05

    The rate-limiting step in branched-chain amino acids (BCAAs) disposal is catalyzed by the mitochondrial branched-chain α-ketoacid dehydrogenase complex (BCKDH). BCKDH activity is regulated mainly by a reversible dephosphorylation (activation)/phosphorylation (inactivation) cycle catalyzed by a specific phosphatase (BDP) and kinase (BDK). Current catalytic activity of BCKDH, described as BCKDH activity state, and thus also BCAAs catabolic rate depend directly on the portion of BCKDH occurring in its active dephosphorylated form. Liver BCKDH activity state alters in response to different nutritional factors. Feeding rats a low-protein diet decreases BCKDH activity. It has been previously shown that lipid lowering drugs, fibrates upregulate liver BCKDH activity and stimulate BCAAs catabolism, especially under the condition of dietary protein deprivation. Effect of statins on liver BCKDH activity has not been studied yet. The present study was aimed at investigating the in vivo effect of simvastatin on liver BCKDH activity, as well as E1, E2 and BDP and BDK mRNA levels in rats fed with either a standard (23% protein) or a low protein (8% protein) diet. For 14 days, simvastatin (80 mg/kg b wt/day) or the vehicle (0.3% methylcellulose) were administrated orally by gavage to the treated and control groups, respectively. The actual BCKDH and total BCKDH activities were assayed spectrophotometrically prior to and following incubation with lambda phosphatase, respectively. The mRNA levels of the selected genes were quantified by means of a semi-quantitative RT-PCR. In rats fed with the low protein diet simvastatin administration reversed physiological adaptation of liver BCKDH to protein restriction and increased liver BCKDH activity state by 39% (p<0.05). Changes in BCKDH activity did not correspond to any changes in mRNA levels for BCKDH catalytic and regulatory enzymes. On the contrary, in rats fed with standard diet liver BCKDH activity state did not alter substantially

  9. Predialysis chronic kidney disease correlates with increased risk of pyogenic liver abscess: a population-based cohort study.

    PubMed

    Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

    2017-10-01

    The incidence of pyogenic liver abscess in Taiwan appears to be much higher than that in western countries. However, little is known about the incidence of pyogenic liver abscess among patients with predialysis chronic kidney disease. The objective of this study was to assess the association between predialysis chronic kidney disease and the risk of pyogenic liver abscess in Taiwan. This population-based, retrospective, cohort study was conducted to analyse the database of the Taiwan National Health Insurance Program. There were 81118 subjects aged 20-84 years with newly diagnosed chronic kidney disease as the predialysis chronic kidney disease group since 2000-2010, and 81118 randomly selected subjects without chronic kidney disease as the nonchronic kidney disease group. The predialysis chronic kidney disease group and the nonchronic kidney disease group were matched with sex, age and comorbidities. The incidence of pyogenic liver abscess at the end of 2013 was calculated in both groups. Subjects who currently received dialysis therapy before the endpoint were excluded from the study. The multivariable Cox proportional hazards regression model was used to assess the hazard ratio (HR) and 95% confidence interval (CI) for the risk of pyogenic liver abscess associated with predialysis chronic kidney disease and other comorbidities including alcohol-related disease, biliary stone, chronic liver disease and diabetes mellitus. The overall incidence of pyogenic liver abscess was 1·65-fold higher in the predialysis chronic kidney disease group than that in the nonchronic kidney disease group (1·38 vs. 0·83 per 1000 person-years, 95% CI 1·59, 1·71). After adjustment for covariables, the adjusted HR of pyogenic liver abscess was 1·51(95% CI 1·30, 1·76) for the predialysis chronic kidney disease group, comparing with the nonchronic kidney disease group. In addition, the adjusted HR would increase to 3·31 (95% CI 2·61, 4·19) for subjects with predialysis chronic

  10. Aroclor 1254 increases the genotoxicity of several carcinogens to liver primary cell cultures

    SciTech Connect

    Mendoza-Figueroa, T.; Lopez-Revilla, R.; Villa-Trevino, S.

    1985-01-01

    The genotoxicity of both direct-acting and precarcinogenic chemicals was evaluated in liver primary cell cultures (LPCC) from untreated and Aroclor 1254 (Ar) pretreated rats. Hepatocytes were isolated from partially hepatectomized rats and their DNA was labeled in vitro with (/sup 3/H) dThd; the molecular weight of single-stranded DNA was determined by alkaline sucrose sedimentation. Two parameters of DNA damage were defined: 1) the mean effective dose (ED50), i.e., the carcinogen concentration that decreased the DNA molecular weight to half the original, and 2) the DNA breaking potency (DBP), i.e., the number of breaks per DNA molecule produced by 2 h exposure to 1mM concentration of the chemical. Two hours exposure of LPCC from untreated rats to the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (6.8-340..mu..M) and to the precarcinogens benzo(a)pyrene (BaP) (0.05-0.33 mM) and dimethylnitrosamine (DMN) (0.45-16 mM) produced a concentration-dependent decrease in the molecular weight of DNA. Pretreatment of rats with Ar decreased significantly the sedimentation velocity of DNA and increased five, three, and two times the DBP of MNNG, BaP, and DMN, respectively. These results show that Ar-pretreatment of rats increases the genotoxicity of both direct-acting and precarcinogenic chemicals and suggest that Ar might increase the genotoxicity of chemical carcinogens perhaps by enhancing their metabolic activation, by producing direct genotoxic effects, or both. Our results also emphasize the carcinogenic risk that the environmental pollution by polychlorinated biphenyls might represent to humans.

  11. Inaccurate preoperative imaging assessment on biliary anatomy not increases biliary complications after living donor liver transplantation.

    PubMed

    Xu, Xiao; Wei, Xuyong; Ling, Qi; Wang, Kai; Bao, Haiwei; Xie, Haiyang; Zhou, Lin; Zheng, Shusen

    2012-04-01

    Accurate assessment of graft bile duct is important to plan surgical procedure. Magnetic resonance cholangiopancreatography (MRCP) has become an important diagnostic procedure in evaluation of pancreaticobiliary ductal abnormalities and has been reported as highly accurate. We aim to estimate the efficacy of preoperative MRCP on depicting biliary anatomy in living donor liver transplantation (LDLT), and to determine whether inaccurate preoperative imaging assessment would increase the biliary complications after LDLT. The data of 118 cases LDLT were recorded. Information from preoperative MRCP was assessed using intraoperative cholangiography (IOC) as the gold standard. The possible risk factors of recipient biliary complications were analyzed. Of 118 donors, 84 had normal anatomy (type A) and 34 had anatomic variants (19 cases of type B, 9 cases of type C, 1 case of type E, 2 cases of type F and 3 cases of type I) confirmed by IOC. MRCP correctly predicted all 84 normal cases and 17 of 34 variant cases, and showed an accuracy of 85.6% (101/118). The incidence of biliary complications was comparable between cases with accurate and inaccurate classification of biliary tree from MRCP, and between cases with normal and variant anatomy of bile duct. While cases with graft duct opening ≤5mm showed a significant higher incidence of total biliary complications (21.1% vs. 6.6%, P=0.028) and biliary stricture (10.5% vs. 1.6%, P=0.041) compared with cases with large duct opening >5mm. MRCP could correctly predict normal but not variant biliary anatomy. Inaccurate assessment of biliary anatomy from MRCP not increases the rate of biliary complications, while small-sized graft duct may cause an increase in biliary complications particularly biliary stricture after LDLT. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Increased risk of chronic liver disease in patients with bipolar disorder: A population-based study.

    PubMed

    Hsu, Jer-Hwa; Chien, I-Chia; Lin, Ching-Heng

    2016-01-01

    This study aimed to investigate the prevalence and incidence of chronic liver disease in patients with bipolar disorder. We used a random sample of 766,427 subjects aged ≥18 years from the National Health Research Institute database in the year 2005. Subjects with at least one primary diagnosis of bipolar disorder in 2005 were identified. Patients with a primary or secondary diagnosis of chronic liver disease were also defined. We compared the prevalence and associated factors of chronic liver disease between patients with bipolar disorder and the general population in 2005. We also compared the incidence of chronic liver disease in patients with bipolar disorder and the general population from 2006 to 2010. The prevalence of chronic liver disease in patients with bipolar disorder (13.9%) was 2.68 times higher than that of the general population (5.8%) in 2005. The average annual incidence of chronic liver disease in patients with bipolar disorder from 2006 to 2010 was also higher than that of the general population (2.95% vs. 1.73%; risk ratio: 1.71; 95% confidence interval: 1.46-2.01). Patients with bipolar disorder had a significantly higher prevalence and incidence of chronic liver disease than those in the general population, and younger patients with bipolar disorder have a much higher prevalence and incidence than those in the general population. Male sex, second-generation antipsychotic or antidepressant use, and hyperlipidemia were associated factors for chronic liver disease in patients with bipolar disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Increased Contracaecum osculatum infection in Baltic cod (Gadus morhua) livers (1982-2012) associated with increasing grey seal (Halichoerus gryphus) populations.

    PubMed

    Haarder, Simon; Kania, Per W; Galatius, Anders; Buchmann, Kurt

    2014-07-01

    Grey seals (Halichoerus gryphus), the main final host of the gastric parasitic nematode Contracaecum osculatum in the Baltic, have recently recolonized the southwestern Baltic Sea. This colonization could lead to an increase in prevalence and intensity of third-stage larvae of C. osculatum in livers of Baltic cod (Gadus morhua), which serve as transport host for this helminth. We performed a parasitologic study of cod in spring 2012 and compared the results with previously unpublished data from 1982/1983. Additionally, grey seals were counted annually from 2000 to 2011 at three haul-out sites in the southwestern Baltic. Of 97 cod livers examined in the 1982/1983 survey, 22% harbored C. osculatum larvae, whereas 55.1% of the examined cod livers (n=185) were infected in 2012; the mean intensity and mean abundance increased from 4.3 and 0.9 to 20.2 and 11.1, respectively. Molecular identification (PCR) confirmed the identity of the larvae. The grey seal population increased markedly during the 12-yr period. We suggest that the elevated parasitism of cod livers is associated with the successful re-establishment of grey seals in the southwestern Baltic.

  14. Increased Soluble Leptin Receptor Levels in Morbidly Obese Patients With Insulin Resistance and Nonalcoholic Fatty Liver disease

    PubMed Central

    Medici, Valentina; Ali, Mohamed R.; Seo, Suk; Aoki, Christopher A.; Rossaro, Lorenzo; Kim, Kyoungmi; Fuller, Will D.; Vidovszky, Tamas J.; Smith, William; Jiang, Joy X.; Maganti, Kalyani; Havel, Peter J.; Kamboj, Amit; Ramsamooj, Rajendra; Török, Natalie J.

    2016-01-01

    The adipocyte hormone, leptin has been demonstrated to have profibrogenic actions in vitro and in animal models. However, no correlation was found between plasma leptin levels and fibrosis stage in humans. Thus, our aim was to study whether soluble leptin receptor (SLR) or free leptin index (FLI; calculated as the ratio of leptin to SLR), may correlate better with the features of metabolic syndrome and with the histological grade and stage of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). We studied a population (n = 104) of morbidly obese patients undergoing bariatric surgery. Data including BMI, type 2 diabetes mellitus, hypertension, and hyperlipidemia were obtained. Plasma fasting leptin and SLR, fasting glucose and insulin were measured, and homeostasis model of assessment insulin resistance (HOMAIR) index and FLI were calculated. All patients had intraoperative liver biopsies. Leptin levels correlated with the BMI. The multiple regression analysis indicated that increasing HOMA and decreasing FLI were predictors of steatosis in the liver (P < 0.0003). SLR levels were positively correlated with the presence of diabetes mellitus and the stage of fibrosis. In conclusion, increased SLR levels in morbidly obese patients with diabetes are correlated with the stage of liver fibrosis, and may reflect progressive liver disease. PMID:20448542

  15. Dietary selenomethionine increases exon-specific DNA methylation of the p53 gene in rat liver and colon mucosa.

    PubMed

    Zeng, Huawei; Yan, Lin; Cheng, Wen-Hsing; Uthus, Eric O

    2011-08-01

    The regulation of site-specific DNA methylation of tumor suppressor genes has been considered as a leading mechanism by which certain nutrients exert their anticancer property. This study was to investigate whether selenium (Se) affects the methylation of globe genomic DNA and the exon-specific p53 gene. Three groups of rats (n = 6-7/group) were fed the AIN-93G basal diet supplemented with 0 [Se deficient (D)], 0.15 [Se adequate (A)], or 4 mg [Se supranutritional (S)] (Se as l-selenomethionine)/kg diet for 104 d, respectively. Rats fed the A or S diet had greater plasma and liver glutathione peroxidase activity, liver thioredoxin reductase activity, and plasma homocysteine concentration than those fed the D diet. However, compared with the A diet, rats fed the S diet did not further increase these Se-dependent enzyme activities or homocysteine concentration. In contrast, Se concentrations in kidney, liver, gastrocnemius muscle, and plasma were increased in a Se-dose-dependent manner. Interestingly, rats fed the S diet had significantly less global liver genomic DNA methylation than those fed the D diet. However, the S diet significantly increased the methylation of the p53 gene (exons 5-8) but not the β-actin gene (exons 2-3) DNA in liver and colon mucosa compared with those fed the D diet. Taken together, long-term Se consumption not only affects selenoprotein enzyme activities, homocysteine, tissue Se concentrations, and global genomic DNA methylation but also increases exon-specific DNA methylation of the p53 gene in a Se-dose-dependent manner in rat liver and colon mucosa.

  16. Annual Report to the Nation on the Status of Cancer, 1975–2012, Featuring the Increasing Incidence of Liver Cancer

    PubMed Central

    Ryerson, A. Blythe; Eheman, Christie R.; Altekruse, Sean F.; Ward, John W.; Jemal, Ahmedin; Sherman, Recinda L.; Henley, S. Jane; Holtzman, Deborah; Lake, Andrew; Noone, Anne-Michelle; Anderson, Robert N.; Ma, Jiemin; Ly, Kathleen N.; Cronin, Kathleen A.; Penberthy, Lynne; Kohler, Betsy A.

    2016-01-01

    BACKGROUND Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers. METHODS Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC’s National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992–2012 and mortality for 1975–2012) and short-term trends (2008–2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the disease. By using NCHS multiple causes of death data, hepatitis C virus (HCV) and liver cancer-associated death rates were examined from 1999 through 2013. RESULTS Among men and women of all major racial and ethnic groups, death rates continued to decline for all cancers combined and for most cancer sites; the overall cancer death rate (for both sexes combined) decreased by 1.5% per year from 2003 to 2012. Overall, incidence rates decreased among men and remained stable among women from 2003 to 2012. Among both men and women, deaths from liver cancer increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Among non-Hispanic (NH) white, NH black, and Hispanic men and women, liver cancer incidence

  17. Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer.

    PubMed

    Ryerson, A Blythe; Eheman, Christie R; Altekruse, Sean F; Ward, John W; Jemal, Ahmedin; Sherman, Recinda L; Henley, S Jane; Holtzman, Deborah; Lake, Andrew; Noone, Anne-Michelle; Anderson, Robert N; Ma, Jiemin; Ly, Kathleen N; Cronin, Kathleen A; Penberthy, Lynne; Kohler, Betsy A

    2016-05-01

    Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers. Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC's National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2012 and mortality for 1975-2012) and short-term trends (2008-2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the disease. By using NCHS multiple causes of death data, hepatitis C virus (HCV) and liver cancer-associated death rates were examined from 1999 through 2013. Among men and women of all major racial and ethnic groups, death rates continued to decline for all cancers combined and for most cancer sites; the overall cancer death rate (for both sexes combined) decreased by 1.5% per year from 2003 to 2012. Overall, incidence rates decreased among men and remained stable among women from 2003 to 2012. Among both men and women, deaths from liver cancer increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Among non-Hispanic (NH) white, NH black, and Hispanic men and women, liver cancer incidence rates were higher for persons born

  18. Increased absorbed liver dose in Selective Internal Radiation Therapy (SIRT) correlates with increased sphere-cluster frequency and absorbed dose inhomogeneity.

    PubMed

    Högberg, Jonas; Rizell, Magnus; Hultborn, Ragnar; Svensson, Johanna; Henrikson, Olof; Mölne, Johan; Gjertsson, Peter; Bernhardt, Peter

    2015-12-01

    The higher tolerated mean absorbed dose for selective internal radiation therapy (SIRT) with intra-arterially infused (90)Y microspheres compared to external beam therapy is speculated to be caused by absorbed dose inhomogeneity, which allows for liver regeneration. However, the complex liver microanatomy and rheology makes modelling less valuable if the tolerance doses are not based on the actual microsphere distribution. The present study demonstrates the sphere distribution and small-scale absorbed dose inhomogeneity and its correlation with the mean absorbed dose in liver tissue resected after SIRT. A patient with marginally resectable cholangiocarcinoma underwent SIRT 9 days prior to resection including adjacent normal liver tissue. The resected specimen was formalin-fixed and sliced into 1 to 2-mm sections. Forty-one normal liver biopsies 6-8 mm in diameter were punched from these sections and the radioactivity measured. Sixteen biopsies were further processed for detailed analyses by consecutive serial sectioning of 15 30-μm sections per biopsy, mounted and stained with haematoxylin-eosin. All sections were scrutinised for isolated or conglomerate spheres. Small-scale dose distributions were obtained by applying a (90)Y-dose point kernel to the microsphere distributions. A total of 3888 spheres were found in the 240 sections. Clusters were frequently found as strings in the arterioles and as conglomerates in small arteries, with the largest cluster comprising 453 spheres. An increased mean absorbed dose in the punch biopsies correlated with large clusters and a greater coefficient of variation. In simulations the absorbed dose was 5-1240 Gy; 90% were 10-97 Gy and 45% were <30 Gy, the assumed tolerance in external beam therapy. Sphere clusters were located in both arterioles and small arteries and increased in size with increasing sphere concentration, resulting in increased absorbed dose inhomogeneity, which contradicts earlier modelling studies.

  19. Low sphingosine-1-phosphate plasma levels are predictive for increased mortality in patients with liver cirrhosis

    PubMed Central

    Bartels, Michael; Scholz, Markus; Seehofer, Daniel; Berg, Thomas; Engelmann, Cornelius; Thiery, Joachim; Ceglarek, Uta

    2017-01-01

    Background & aim The association of circulating sphingosine-1-phosphate (S1P), a bioactive lipid involved in various cellular processes, and related metabolites such as sphinganine-1-phosphate (SA1P) and sphingosine (SPH) with mortality in patients with end-stage liver disease is investigated in the presented study. S1P as a bioactive lipid mediator, is involved in several cellular processes, however, in end-stage liver disease its role is not understood. Methods The study cohort consisted of 95 patients with end-stage liver disease and available information on one-year outcome. The median MELD (Model for end-stage liver disease) score was 12.41 (Range 6.43–39.63). The quantification of sphingolipids in citrated plasma specimen was performed after methanolic protein precipitation followed by hydrophilic interaction liquid chromatography and tandem mass spectrometric detection. Results S1P and SA1P displayed significant correlations with the MELD score. Patients with circulating S1P levels below the lowest tertile (110.68 ng/ml) showed the poorest one-year survival rate of only 57.1%, whereas one-year survival rate in patients with S1P plasma levels above 165.67 ng/ml was 93.8%. In a multivariate cox regression analysis including platelet counts, concentrations of hemoglobin and MELD score, S1P remained a significant predictor for three-month and one-year mortality. Conclusions Low plasma S1P concentrations are highly significantly associated with prognosis in end-stage liver disease. This association is independent of the stage of liver disease. Further studies should be performed to investigate S1P, its role in the pathophysiology of liver diseases and its potential for therapeutic interventions. PMID:28334008

  20. Swim training increases glucose output from liver perfused in situ with glucagon in fed and fasted rats.

    PubMed

    Drouin, Réjean; Robert, Geneviève; Milot, Martin; Massicotte, Denis; Péronnet, François; Lavoie, Carole

    2004-08-01

    The effect of endurance swim training (3 hours per day, 5 days/week, for 10 weeks) on hepatic glucose production (HGP) in liver perfused in situ for 60 minutes with glucagon and insulin was studied in Sprague-Dawley rats. The experiments were performed in fed rats and in rats fasted for 24 hours, but with lactate (8 mmol/L) added to the perfusion medium. Liver glycogen content was significantly lower in fasted than fed rats (fasted untrained and trained: 14 +/- 4 and 11 +/- 3 micromol glycosyl U/g of liver wet weight (WW); fed untrained and trained: 205 +/- 11 and 231 +/- 11 micromol glycosyl U/g of liver WW; not significantly different in trained and untrained rats). Glucagon increased HGP in the 4 experimental groups, but the increases were more rapid and pronounced in trained than in untrained rats in both fed and fasted states. HGP values (area under the curve [AUC] in micromol/g of liver WW) were significantly higher in trained fed (112.1 +/- 7.1 v 85.9 +/- 12.2 in untrained rats) than in trained fasted rats (50.8 +/- 4.4 v 34.7 +/- 3.6 in untrained rats). When compared with untrained rats, the total amount of glucose released by the liver in response to glucagon in trained rats was approximately 30% higher in the fed state and approximately 45% larger in the fasted state. These results indicate that endurance training increases the response of both glycogenolysis and gluconeogenesis to glucagon.

  1. [Non-alcoholic fatty liver disease in children and adolescents].

    PubMed

    Björklund, Jessica; Laursen, Tea Lund; Kazankov, Konstantin; Thomsen, Karen Louise; Hamilton-Dutoit, Stephen; Stenbøg, Elisabeth; Grønbæk, Henning

    2017-07-03

    Non-alcoholic fatty liver disease (NAFLD) is characterized by liver fat accumulation and non-alcoholic steatohepatitis (NASH) with inflammation and fibrosis, which may lead to cirrhosis also in childhood. NAFLD/NASH in children are related to obesity and the metabolic syndrome, and incidence and prevalence are expected to increase. Children having liver steatosis and elevated liver enzymes are most often asymptomatic, and a liver biopsy is necessary for correct diagnosis and staging. The treatment should focus on lifestyle changes, as pharmacological therapy needs further evaluation.

  2. Liver pathology associated with increased mortality in turkey breeder and meat turkey flocks.

    PubMed

    Popp, Christina; Hauck, Rüdiger; Vahlenkamp, Thomas W; Lüschow, Dörte; Kershaw, B Olivia; Hoferer, Marc; Hafez, Hafez M

    2014-09-01

    Between 2006 and 2011 a series of disease conditions characterized by raised mortality and liver disorders occurred in turkey breeder flocks and in meat turkey flocks in Germany. The flocks were between 12 and 23 wk of age, and mostly hens were affected. Clinical signs were nonspecific and accompanied by mortality varying between 1% and 7%. Affected birds displayed swollen livers that were marbled with black and red spots and yellowish areas. The pericardium was filled with an amber fluid, and the coronary groove was extensively filled with fat. Spleens were swollen, and a serous fluid that seemed to leak from the liver was present in the body cavity. Histopathological findings in all but one case included fatty degeneration of hepatocytes with parenchymal collapse and associated hemorrhages. Some animals showed cholangitis and hepatitis with intranuclear inclusion bodies. In three cases with breeders, electron microscopy detected virus particles that were between 23 and 30 nm and similar to parvo- or picornavirus. In addition, picornavirus RNA was detected in the livers of one meat turkey flock. Investigations by PCR for circovirus, polyomavirus parvovirus, and aviadenovirus yielded negative results in all cases, but an aviadenovirus was isolated from livers twice and a reovirus from the intestines once. Supplementation with vitamin E and selenium seemed to improve the situation. The most likely diagnosis is lipidosis, a metabolic disorder with complex etiology, which has rarely been described in turkeys.

  3. Increased expression of regulatory Tr1 cells in recurrent hepatitis C after liver transplantation.

    PubMed

    Carpentier, A; Conti, F; Stenard, F; Aoudjehane, L; Miroux, C; Podevin, P; Morales, O; Chouzenoux, S; Scatton, O; Groux, H; Auriault, C; Calmus, Y; Pancre, V; Delhem, N

    2009-09-01

    Immune response failure during HCV infection has been associated with the activity of regulatory T cells. Hepatitis C-related cirrhosis is the main reason for liver transplantation. However, 80% of transplanted patients present an accelerated recurrence of the disease. This study assessed the involvement of regulatory T-cell subsets (CD4+CD25+ cells: 'Treg' and CD49b+CD18+ cells: 'T regulatory-1' cells), in the recurrence of HCV after liver transplantation, using transcriptomic analysis, ELISA assays on serum samples and immunohistochemistry on liver biopsies from liver recipients 1 and 5 years after transplantation. Three groups of patients were included: stable HCV-negative recipients and those with mild and severe hepatitis C recurrence. At 5 years, Treg markers were overexpressed in all HCV+ recipients. By contrast, Tr1 markers were only overexpressed in patients with severe recurrence. At 1 year, a trend toward the overexpression of Tr1 was noted in patients evolving toward severe recurrence. IL-10 production, a characteristic of the Tr1 subset, was enhanced in severe recurrence at both 1 and 5 years. These results suggest that Tr1 are enhanced during severe HCV recurrence after liver transplantation and could be predictive of HCV recurrence. High levels of IL-10 at 1 year could be predictive of severe recurrence, and high IL-10 producers might warrant more intensive management.

  4. Genetic inhibition of hepatic acetyl-CoA carboxylase activity increases liver fat and alters global protein acetylationa

    PubMed Central

    Chow, Jenny D.Y.; Lawrence, Robert T.; Healy, Marin E.; Dominy, John E.; Liao, Jason A.; Breen, David S.; Byrne, Frances L.; Kenwood, Brandon M.; Lackner, Carolin; Okutsu, Saeko; Mas, Valeria R.; Caldwell, Stephen H.; Tomsig, Jose L.; Cooney, Gregory J.; Puigserver, Pere B.; Turner, Nigel; James, David E.; Villén, Judit; Hoehn, Kyle L.

    2014-01-01

    Lipid deposition in the liver is associated with metabolic disorders including fatty liver disease, type II diabetes, and hepatocellular cancer. The enzymes acetyl-CoA carboxylase 1 (ACC1) and ACC2 are powerful regulators of hepatic fat storage; therefore, their inhibition is expected to prevent the development of fatty liver. In this study we generated liver-specific ACC1 and ACC2 double knockout (LDKO) mice to determine how the loss of ACC activity affects liver fat metabolism and whole-body physiology. Characterization of LDKO mice revealed unexpected phenotypes of increased hepatic triglyceride and decreased fat oxidation. We also observed that chronic ACC inhibition led to hyper-acetylation of proteins in the extra-mitochondrial space. In sum, these data reveal the existence of a compensatory pathway that protects hepatic fat stores when ACC enzymes are inhibited. Furthermore, we identified an important role for ACC enzymes in the regulation of protein acetylation in the extra-mitochondrial space. PMID:24944901

  5. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis.

    PubMed

    Dulai, Parambir S; Singh, Siddharth; Patel, Janki; Soni, Meera; Prokop, Larry J; Younossi, Zobair; Sebastiani, Giada; Ekstedt, Mattias; Hagstrom, Hannes; Nasr, Patrik; Stal, Per; Wong, Vincent Wai-Sun; Kechagias, Stergios; Hultcrantz, Rolf; Loomba, Rohit

    2017-05-01

    Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD. Through a systematic review and meta-analysis, we identified five adult NAFLD cohort studies reporting fibrosis stage-specific mortality (0-4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRRs) with 95% confidence intervals (CIs) for all-cause and liver-related mortality were estimated. The study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Included were 1,495 NAFLD patients with 17,452 patient years of follow-up. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all-cause mortality, and this risk increased with increases in the stage of fibrosis: stage 1, MRR = 1.58 (95% CI 1.19-2.11); stage 2, MRR = 2.52 (95% CI 1.85-3.42); stage 3, MRR = 3.48 (95% CI 2.51-4.83); and stage 4, MRR = 6.40 (95% CI 4.11-9.95). The results were more pronounced as the risk of liver-related mortality increased exponentially with each increase in the stage of fibrosis: stage 1, MRR = 1.41 (95% CI 0.17-11.95); stage 2, MRR = 9.57 (95% CI 1.67-54.93); stage 3, MRR = 16.69 (95% CI 2.92-95.36); and stage 4, MRR = 42.30 (95% CI 3.51-510.34). Limitations of the study include an inability to adjust for comorbid conditions or demographics known to impact fibrosis progression in NAFLD and the inclusion of patients with simple steatosis and nonalcoholic steatohepatitis without fibrosis in the reference comparison group. The risk of liver-related mortality increases exponentially with increase in fibrosis stage; these data have important implications in assessing the utility of each stage and benefits of regression of fibrosis

  6. Increased CD163 expression is associated with acute-on-chronic hepatitis B liver failure

    PubMed Central

    Ye, Hong; Wang, Li-Yuan; Zhao, Jing; Wang, Kai

    2013-01-01

    AIM: To assess CD163 expression in plasma and peripheral blood and analyze its association with disease in acute-on-chronic hepatitis B liver failure (ACHBLF) patients. METHODS: A retrospective study was conducted from January 1, 2011 to January 1, 2012. Forty patients with ACHBLF (mean age 44.48 ± 12.28 years, range 18-69 years), 40 patients with chronic hepatitis B (CHB) (mean age 39.45 ± 12.22 years, range 21-57 years) and 20 age- and sex-matched healthy controls (mean age 38.35 ± 11.97 years, range 28-60 years) were included in this study. Flow cytometry was used to analyze the frequency of CD163+ peripheral blood mononuclear cells (PBMCs) and surface protein expression of CD163. Real-time transcription-polymerase chain reaction was performed to assess relative CD163 mRNA levels in PBMCs. Plasma soluble CD163 (sCD163) levels were measured by enzyme-linked immunosorbent assay. Clinical variables were also recorded. Comparisons between groups were analyzed by Kruskal-Wallis H test and Mann-Whitney U test. Statistical analyses were performed using SPSS 15.0 software and a P value < 0.05 was considered statistically significant. RESULTS: Flow cytometry showed that the population of CD163+ PBMCs was significantly greater in ACHBLF patients than in CHB patients and healthy controls (47.9645% ± 17.1542%, 32.0975% ± 11.0215% vs 17.9460% ± 6.3618%, P < 0.0001). However, there were no significant differences in mean fluorescence intensity of CD163+ PBMCs within the three groups (27.4975 ± 11.3731, 25.8140 ± 10.0649 vs 20.5050 ± 6.2437, P = 0.0514). CD163 mRNA expression in ACHBLF patients was significantly increased compared with CHB patients and healthy controls (1.41 × 10-2 ± 2.18 × 10-2, 5.10 × 10-3 ± 3.61 × 10-3 vs 37.0 × 10-4 ± 3.55 × 10-4, P = 0.02). Plasma sCD163 levels in patients with ACHBLF were significantly increased compared with CHB patients and healthy controls (4706.2175 ± 1681.1096 ng/mL, 1089.7160 ± 736.8395 ng/mL vs 435.9562 ± 440

  7. Increased CD163 expression is associated with acute-on-chronic hepatitis B liver failure.

    PubMed

    Ye, Hong; Wang, Li-Yuan; Zhao, Jing; Wang, Kai

    2013-05-14

    To assess CD163 expression in plasma and peripheral blood and analyze its association with disease in acute-on-chronic hepatitis B liver failure (ACHBLF) patients. A retrospective study was conducted from January 1, 2011 to January 1, 2012. Forty patients with ACHBLF (mean age 44.48 ± 12.28 years, range 18-69 years), 40 patients with chronic hepatitis B (CHB) (mean age 39.45 ± 12.22 years, range 21-57 years) and 20 age- and sex-matched healthy controls (mean age 38.35 ± 11.97 years, range 28-60 years) were included in this study. Flow cytometry was used to analyze the frequency of CD163+ peripheral blood mononuclear cells (PBMCs) and surface protein expression of CD163. Real-time transcription-polymerase chain reaction was performed to assess relative CD163 mRNA levels in PBMCs. Plasma soluble CD163 (sCD163) levels were measured by enzyme-linked immunosorbent assay. Clinical variables were also recorded. Comparisons between groups were analyzed by Kruskal-Wallis H test and Mann-Whitney U test. Statistical analyses were performed using SPSS 15.0 software and a P value < 0.05 was considered statistically significant. Flow cytometry showed that the population of CD163+ PBMCs was significantly greater in ACHBLF patients than in CHB patients and healthy controls (47.9645% ± 17.1542%, 32.0975% ± 11.0215% vs 17.9460% ± 6.3618%, P < 0.0001). However, there were no significant differences in mean fluorescence intensity of CD163+ PBMCs within the three groups (27.4975 ± 11.3731, 25.8140 ± 10.0649 vs 20.5050 ± 6.2437, P = 0.0514). CD163 mRNA expression in ACHBLF patients was significantly increased compared with CHB patients and healthy controls (1.41 × 10⁻² ± 2.18 × 10⁻², 5.10 × 10⁻³ ± 3.61 × 10⁻³ vs 37.0 × 10⁻⁴ ± 3.55 × 10⁻⁴, P = 0.02). Plasma sCD163 levels in patients with ACHBLF were significantly increased compared with CHB patients and healthy controls (4706.2175 ± 1681.1096 ng/mL, 1089.7160 ± 736.8395 ng/mL vs 435.9562 ± 440

  8. Post–Liver Transplant Delirium Increases Mortality and Length of Stay

    PubMed Central

    Oliver, Nathan; Bohorquez, Humberto; Anders, Stephanie; Freeman, Andrew; Fine, Kerry; Ahmed, Emily; Bruce, David S.; Carmody, Ian C.; Cohen, Ari J.; Seal, John; Reichman, Trevor W.; Loss, George E.

    2017-01-01

    Background: Incidence of delirium after liver transplantation (LT) has been reported to occur in 10%-47% of patients and is associated with increased hospital and intensive care unit lengths of stay and poor outcomes. Methods: Our primary objective was to evaluate the incidence and predisposing risk factors for developing delirium after LT. Our secondary objectives were to describe how delirium is managed in patients after LT, to examine the utilization of resources associated with delirium after LT, and to analyze the outcomes of patients who were treated for delirium after LT. Results: In a population of 181 consecutive patients who received an LT, 38 (21.0%) developed delirium. In the multivariate analysis, delirium was associated with pretransplant use of antidepressants (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.29-8.70) and pretransplant hospital admission for encephalopathy (OR 4.39, 95% CI 1.77-10.9). Patients with delirium spent more time on mechanical ventilation (2.0 vs 1.3 days, P=0.008) and had longer intensive care unit stays (4.6 vs 2.7 days, P=0.008), longer hospital stays (27.6 vs 11.2 days, P=0.003), and higher 6-month mortality (13.2% vs 1.4%, P=0.003) than patients who did not develop delirium. Conclusion: The presence of delirium is common after LT and is associated with high morbidity and mortality within the first 6 months posttransplant. Pretransplant factors independently associated with developing delirium after LT include prior use of antidepressants and pretransplant hospital admission for encephalopathy. Efforts should be made to identify patients at risk for delirium, as protocol-based management may improve outcomes in a cost-effective manner. PMID:28331444

  9. Exposure to industrial wideband noise increases connective tissue in the rat liver.

    PubMed

    Oliveira, Maria João R; Freitas, Diamantino; Carvalho, António P O; Guimarães, Laura; Pinto, Ana; Águas, Artur P

    2012-01-01

    Rats were daily exposed (eight hours/day) for a period of four weeks to the same high-intensity wideband noise that was recorded before in a large textile plant. Histologic observation of liver sections of the rats was used to perform quantitative comparison of hepatic connective tissue (dyed by Masson trichromic staining) between the noise-exposed and control animals. For that, we have photographed at random centrolobular areas of stained rat liver sections. We found that noise exposure resulted in significant enhancement in the area of collagen-rich connective tissue present in the centrolobular domain of the rat liver. Our data strengthen previous evidence showing that fibrotic transformation is a systemic effect of chronic exposure of rodents and humans to industrial wideband noise.

  10. Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors

    PubMed Central

    Gandhi, Chandrashekhar R.; Murase, Noriko; Subbotin, Vladimir M.; Uemura, Tadahiro; Nalesnik, Michael; Demetris, Anthony J.; Fung, John J.; Starzl, Thomas E.

    2010-01-01

    Background/Aims The response to the liver damage caused by portacaval shunt (PCS) is characterized by low-grade hyperplasia and atrophy. To clarify mechanisms of this dissociation, we correlated the expression of ‘hepatotrophic factors’ and the antihepatotrophic and proapoptotic peptide, transforming growth factor (TGF)-β, with the pathologic changes caused by PCS in rats. Methods PCS was created by side-to-side anastomosis between the portal vein and inferior vena cava, with ligation of the hilar portal vein. Hepatic growth mediators were measured to 2 months. Results The decrease in the liver/body weight ratio during the first 7 days which stabilized by day 15, corresponded to parenchymal cell apoptosis and increases in hepatic TGF-β concentration that peaked at 1.4 × baseline at 15 days before returning to control levels by day 30. Variable increases in the concentrations of growth promoters (hepatocyte growth factor, TGF-α and augmenter of liver regeneration) also occurred during the period of hepatocellular apoptosis. Conclusions The development of hepatic atrophy was associated with changes in TGF-β concentration, and occurred despite increased expression of multiple putative growth promoters. The findings suggest that apoptosis set in motion by TGF-β constrains the amount of hepatocyte proliferation independently from control of liver volume. PMID:12175629

  11. Liver failure induces a systemic inflammatory response. Prevention by recombinant N-terminal bactericidal/permeability-increasing protein.

    PubMed Central

    Boermeester, M. A.; Houdijk, A. P.; Meyer, S.; Cuesta, M. A.; Appelmelk, B. J.; Wesdorp, R. I.; Hack, C. E.; Van Leeuwen, P. A.

    1995-01-01

    The observed increased susceptibility of patients with fulminant hepatic failure for local and systemic infections has been hypothesized to be due to a failure for the hepatic clearance function and subsequent leaking of endogenous endotoxins into the systemic circulation. However, experimental evidence for such a systemic inflammation during liver failure due to endogenous endotoxemia is lacking. Therefore, we designed a study to clarify whether circulating endotoxins due to liver failure could lead to the development of systemic inflammations. In a rat model for liver failure induced by a two-thirds partial hepatectomy, we evaluated the course of circulating tumor necrosis factor and interleukin-6, changes in blood chemistry and hemodynamics, and histopathological changes in the lungs. Partially hepatectomized animals, but not sham-operated animals, demonstrated cardiac failure, increased levels of creatinin and urea, metabolic acidosis, high plasma levels of tumor necrosis factor and interleukin-6, and an influx of PMNs in the lungs-together indicating the development of a systemic inflammatory response. Continuous infusion of recombinant N-terminal bactericidal/permeability-increasing protein (rBPI23), a well described endotoxin-neutralizing protein, prevented these inflammatory reactions. Ex vivo experiments with rat plasma samples confirmed the presence of circulating endotoxins in partially hepatectomized rats as opposed to those treated with rBPI23. Thus, our results indicate that the early phase of liver failure induces a systemic inflammatory response triggered by circulating endotoxins, which can be prevented by perioperative infusion of rBPI23. Images Figure 2 PMID:7485405

  12. Increased Mortality from Lung Cancer and Bronchiectasis in Young Adults after Exposure to Arsenic in Utero and in Early Childhood

    PubMed Central

    Smith, Allan H.; Marshall, Guillermo; Yuan, Yan; Ferreccio, Catterina; Liaw, Jane; von Ehrenstein, Ondine; Steinmaus, Craig; Bates, Michael N.; Selvin, Steve

    2006-01-01

    Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta is the second largest city in Chile and had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. This unique exposure scenario provides a rare opportunity to investigate the long-term mortality impact of early-life arsenic exposure. In this study, we compared mortality rates in Antofagasta in the period 1989–2000 with those of the rest of Chile, focusing on subjects who were born during or just before the peak exposure period and who were 30–49 years of age at the time of death. For the birth cohort born just before the high-exposure period (1950–1957) and exposed in early childhood, the standardized mortality ratio (SMR) for lung cancer was 7.0 [95% confidence interval (CI), 5.4–8.9; p < 0.001] and the SMR for bronchiectasis was 12.4 (95% CI, 3.3–31.7; p < 0.001). For those born during the high-exposure period (1958–1970) with probable exposure in utero and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.5–9.9; p < 0.001) for lung cancer and 46.2 (95% CI, 21.1–87.7; p < 0.001) for bronchiectasis. These findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease. PMID:16882542

  13. Evidence for Increased 5α-Reductase Activity During Early Childhood in Daughters of Women With Polycystic Ovary Syndrome

    PubMed Central

    Torchen, Laura C.; Idkowiak, Jan; Fogel, Naomi R.; O'Neil, Donna M.; Shackleton, Cedric H. L.; Arlt, Wiebke

    2016-01-01

    Context: Polycystic ovary syndrome (PCOS) is a heritable, complex genetic disease. Animal models suggest that androgen exposure at critical developmental stages contributes to disease pathogenesis. We hypothesized that genetic variation resulting in increased androgen production produces the phenotypic features of PCOS by programming during critical developmental periods. Although we have not found evidence for increased in utero androgen levels in cord blood in the daughters of women with PCOS (PCOS-d), target tissue androgen production may be amplified by increased 5α-reductase activity analogous to findings in adult affected women. It is possible to noninvasively test this hypothesis by examining urinary steroid metabolites. Objective: We performed this study to investigate whether PCOS-d have altered androgen metabolism during early childhood. Design, Setting, and Participants: Twenty-one PCOS-d, 1–3 years old, and 36 control girls of comparable age were studied at an academic medical center. Main Outcome Measures: Urinary steroid metabolites were measured by gas chromatography/mass spectrometry. Twenty-four hour steroid excretion rates and precursor to product ratios suggestive of 5α-reductase and 11β-hydroxysteroid dehydrogenase activities were calculated. Results: Age did not differ but weight for length Z-scores were higher in PCOS-d compared to control girls (P = .02). PCOS-d had increased 5α-tetrahydrocortisol:tetrahydrocortisol ratios (P = .04), suggesting increased global 5α-reductase activity. There was no evidence for differences in 11β-hydroxysteroid dehydrogenase activity. Steroid metabolite excretion was not correlated with weight. Conclusions: Our findings suggest that differences in androgen metabolism are present in early childhood in PCOS-d. Increased 5α-reductase activity could contribute to the development of PCOS by amplifying target tissue androgen action. PMID:26990942

  14. Postoperative delirium is associated with increased intensive care unit and hospital length of stays after liver transplantation.

    PubMed

    Bhattacharya, Bishwajit; Maung, Adrian; Barre, Kimberly; Maerz, Linda; Rodriguez-Davalos, Manuel I; Schilsky, Michael; Mulligan, David C; Davis, Kimberly A

    2017-01-01

    Delirium is increasingly recognized as a common and important postoperative complication that significantly hinders surgical recovery. However, there is a paucity of data examining the incidence and impact of delirium after liver transplantation. Retrospective case series in a tertiary care center examining all (n = 144) adult patients who underwent liver transplantation during a 6-y period. Delirium occurred in 25% of the patients with an average duration of 4.56 d. Patients who developed delirium were older (P = 0.007), had higher preoperative model for end-stage liver disease score (P = 0.019) and longer pretransplant hospital length of stay (LOS; P = 0.003). Patients with delirium were also more likely to have alcohol ingestion as an etiology of the liver failure (P = 0.033). Delirious patients had a trend toward increased ventilator days (P = 0.235) and significantly longer postoperative hospital (P = 0.001) and intensive care unit LOS (P = 0.001). Delirium was also associated with an increased frequency of hospital acquired infections including urinary tract infections (P = 0.005) and pneumonias (P = 0.001). Delirium is a common occurrence among liver transplant patients associated with increased complications and LOSs. Further prospective studies are needed to determine the specific risk factors in this complex population and to determine if delirium has an impact on long-term outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Maternal Depression Increases Childhood Dental Caries: A Cohort Study in Brazil.

    PubMed

    Dos Santos Pinto, Gabriela; de Ávila Quevedo, Luciana; Britto Correa, Marcos; Sousa Azevedo, Marina; Leão Goettems, Marília; Tavares Pinheiro, Ricardo; Demarco, Flávio Fernando

    2017-01-01

    To investigate the relationship between maternal depression and childhood caries in a cohort of adolescent mothers. This cross-sectional study nested in a cohort evaluated a sample of 538 mother/child dyads. When the children were 24-36 months of age, data regarding oral health from children and mothers were collected by clinical dental examination. A mother's major depressive disorder was assessed by using the Mini International Neuropsychiatric Interview (MINI [Plus]), at the current moment. Independent variables were obtained by using questionnaires. The outcome on dental caries experience was dichotomized by using 2 cut points: dmfs ≥1 and dmfs ≥3. Poisson regression analysis, using a hierarchical approach, was applied to assess the association between major depressive disorder in mothers with and those without caries experience and the outcome. The prevalence of dental caries in children was 15.1% (n = 82). The mean dmfs index was 1.12 (SD = 3.72). The prevalence of major depressive disorder was 32.6% (n = 168). An interaction between caries status and depressive disorder was found, and after adjusted analysis, children from mothers with major depressive disorder with negative caries experience presented a higher caries prevalence (prevalence ratio 4.00, 95% confidence interval 1.29-12.41). Our findings suggest that maternal psychiatric disorders could have a negative impact on children's oral health. © 2016 S. Karger AG, Basel.

  16. Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth

    PubMed Central

    Brown, Kristin K.; Evason, Kimberley; Beltz, Sebastian; Tsomides, Allison; O'Connor, Keelin; Galli, Giorgio G.; Yimlamai, Dean; Chhangawala, Sagar; Yuan, Min; Lien, Evan C.; Wucherpfennig, Julia; Nissim, Sahar; Minami, Akihiro; Cohen, David E.; Camargo, Fernando D.; Asara, John M.; Houvras, Yariv; Stainier, Didier Y.R.; Goessling, Wolfram

    2016-01-01

    The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signaling provides the cellular building blocks required for rapid growth. Here, we demonstrate that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 (also known as YAP) develop enlarged livers and are prone to liver tumor formation. Transcriptomic and metabolomic profiling identify that Yap1 reprograms glutamine metabolism. Yap1 directly enhances glutamine synthetase (glul) expression and activity, elevating steady-state levels of glutamine and enhancing the relative isotopic enrichment of nitrogen during de novo purine and pyrimidine biosynthesis. Genetic or pharmacological inhibition of GLUL diminishes the isotopic enrichment of nitrogen into nucleotides, suppresses hepatomegaly and the growth of liver cancer cells. Consequently, Yap-driven liver growth is susceptible to nucleotide inhibition. Together, our findings demonstrate that Yap1 integrates the anabolic demands of tissue growth during development and tumorigenesis by reprogramming nitrogen metabolism to stimulate nucleotide biosynthesis. PMID:27428308

  17. Increased neuronal survival in the brainstem during liver injury: role of γ-aminobutyric acid and serotonin chitosan nanoparticles.

    PubMed

    Shilpa, J; Anitha, M; Paulose, C S

    2013-09-01

    γ-Aminobutyric acid (GABA)- and serotonin (5-HT)-mediated cell signaling, neuronal survival enhancement, and reduced neuronal death in brainstem during liver injury followed by active liver regeneration have a critical role in maintaining routine bodily functions. In the present study, GABAB and 5-HT2A receptor functional regulation, interrelated actions of neuronal survival factors, and expression of apoptotic factors in the brainstem during GABA and 5-HT chitosan nanoparticles-induced active liver regeneration in partially hepatectomized rats were evaluated. Partially hepatectomized rats were treated with the nanoparticles, and receptor assays and confocal microscopic studies of GABAB and 5-HT2A receptors, gene expression studies of GABAB and 5-HT2A receptors, nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), Akt-1, phospholipase C, Bax, and caspase-8 were performed with the brainstems of experimental animals. A significant decrease in GABAB and 5-HT2A receptor numbers and gene expressions denoted a homeostatic adjustment by the brain to trigger the sympathetic innervations during elevated DNA synthesis in the liver. The neuronal apoptosis resulting from the loss of liver function after partial hepatectomy was minimized by nanoparticle treatment in rats compared with rats with no treatment during regeneration. This was confirmed from the gene expression patterns of NF-κB, TNF-α, Akt-1, phospholipase C, Bax, and caspase-8. The present study revealed the potential of GABA and 5-HT chitosan nanoparticles for increasing neuronal survival in the brainstem during liver injury following regeneration, which avoids many neuropsychiatric problems. Copyright © 2013 Wiley Periodicals, Inc.

  18. Mesenchymal Stem Cells Increase Neo-Angiogenesis and Albumin Production in a Liver Tissue-Engineered Engraftment.

    PubMed

    Carraro, Amedeo; Buggio, Maurizio; Gardin, Chiara; Tedeschi, Umberto; Ferroni, Letizia; Zavan, Padova-Barbara

    2016-03-12

    The construction of a three-dimensional (3D) liver tissue is limited by many factors; one of them is the lack of vascularization inside the tissue-engineered construct. An engineered liver pocket-scaffold able to increase neo-angiogenesis in vivo could be a solution to overcome these limitations. In this work, a hyaluronan (HA)-based scaffold enriched with human mesenchymal stem cells (hMSCs) and rat hepatocytes was pre-conditioned in a bioreactor system, then implanted into the liver of rats. Angiogenesis and hepatocyte metabolic functions were monitored. The formation of a de novo vascular network within the HA-based scaffold, as well as an improvement in albumin production by the implanted hepatocytes, were detected. The presence of hMSCs in the HA-scaffold increased the concentration of growth factors promoting angiogenesis inside the graft. This event ensured a high blood vessel density, coupled with a support to metabolic functions of hepatocytes. All together, these results highlight the important role played by stem cells in liver tissue-engineered engraftment.

  19. The role of calcium and nitric oxide during liver enzyme release induced by increased physical forces as evidenced in partially hepatectomized rats.

    PubMed

    Díaz-Juárez, Julieta; Hernández-Muñoz, Rolando

    2011-03-01

    Although increased plasma enzyme activities could be diagnostic for tissue damage, the mechanisms controlling cellular enzyme release remain poorly understood. We found a selective and drastic elevation of serum enzyme activities accompanying rat liver regeneration after partial hepatectomy (PH), apparently controlled by a mechanism dependent on flow-bearing physical forces. In fact, this study assesses a putative role of calcium mobilization and nitric oxide (NO) production underlying rat liver enzyme release. The role of increased shear stress (by enhancing viscosity during perfusion) and the participation of cell calcium and NO were tested in isolated livers subjected to increasing flow rate. After PH, there was a drastic elevation of serum activities for liver enzyme markers, clearly predominating those of mitochondrial localization. Liver enzyme release largely depended on extracellular calcium entry, probably mediated by stretch-sensitive calcium channels, as well as by increasing NO production. However, these effects were differentially observed when comparing liver enzymes from cytoplasmic or mitochondrial compartments. Moreover, a possible role for cell-mediated mechanotransduction in liver enzyme release was suggested by increasing shear stress (high viscosity), which also selectively affected the release of the enzymes tested. Therefore, we show, for the first time, that flow-induced shear stress can control the amount of hepatic enzymes released into the bloodstream, which is largely regulated through modifications in cell calcium mobilization and production of liver NO, events markedly elevated in the proliferating rat liver. Copyright © 2011 American Association for the Study of Liver Diseases.

  20. Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia

    PubMed Central

    Honsawek, Sittisak; Chayanupatkul, Maneerat; Chongsrisawat, Voranush; Vejchapipat, Paisarn; Poovorawan, Yong

    2010-01-01

    AIM: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls. METHODS: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundice status. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children. PMID:21086566

  1. Astragalus membranaceus as a cause of increased CA19-9 and liver and kidney cysts: a case report.

    PubMed

    Tong, X; Xiao, D; Yao, F; Huang, T

    2014-10-01

    Astragalus membranaceus, one of the most common Chinese herbs, is widely used to prevent and treat a variety of diseases. Very few adverse reactions, caused by A. membranaceus, have been reported in the literature. The purpose of this article was to report a case of marked increase in carbohydrate antigen 19-9 (CA19-9) and the formation of liver and kidney cysts following oral administration of A. membranaceus. A 38-year-old woman was found to have a high serum CA19-9 level (156 U/mL) at her routine annual examination. On follow-up, several small cysts were found in her left kidney and liver by CT scan. Her medical history showed that she had taken Astragalus tea every day for 1 month. One month after she stopped taking it, the CA19-9 level decreased to 40·19 U/mL. Ten months later, PET-CT showed that there were no liver and kidney cysts. However, she took Astragalus powder again in the second year and 1 month later her CA19-9 level increased again to more than 1000 U/mL. Several small cysts were again seen in her left kidney and liver by enhanced CT. Her CA19-9 level gradually became normal after she stopped taking the Astragalus powder. This case strongly suggests that oral administration of A. membranaceus may lead to increase in CA19-9 and the formation of liver and kidney cysts. © 2014 John Wiley & Sons Ltd.

  2. Postnatal High-Fat Diet Increases Liver Steatosis and Apoptosis Threatened by Prenatal Dexamethasone through the Oxidative Effect

    PubMed Central

    Huang, Ying-Hsien; Chen, Chih-Jen; Tang, Kuo-Shu; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Tain, You-Lin; Chen, Chih-Cheng; Chu, En-Wei; Li, Shih-Wen; Yu, Hong-Ren; Huang, Li-Tung

    2016-01-01

    The objective of this study was to investigate cellular apoptosis in prenatal glucocorticoid overexposure and a postnatal high fat diet in rats. Pregnant Sprague-Dawley rats at gestational days 14 to 21 were administered saline (vehicle) or dexamethasone and weaned onto either a normal fat diet or a high fat diet for 180 days; in total four experimental groups were designated, i.e., vehicle treated group (VEH), dexamethasone treated group (DEX), vehicle treated plus high-fat diet (VHF), and dexamethasone treated plus high-fat diet (DHF). Chronic effects of prenatal liver programming were assessed at postnatal day 180. The apoptotic pathways involved proteins were analyzed by Western blotting for their expressions. Apoptosis and liver steatosis were also examined by histology. We found that liver steatosis and apoptosis were increased in the DHF, DEX, and VHF treated groups, and that the DHF treated group was increased at higher levels than the DEX and VHF treated groups. The expression of leptin was decreased more in the DHF treated group than in the DEX and VHF treated groups. Decreased peroxisome proliferator-activated receptor-gamma coactivator 1α, phosphoinositide-3-kinase, manganese superoxide dismutase and increased malondialdehyde expression levels were seen in DHF treated group relative to the DEX treated group. The DHF treated group exhibited higher levels of oxidative stress, apoptosis and liver steatosis than the DEX treated group. These results indicate that the environment of high-fat diet plays an important role in the development of liver injury after prenatal stress. PMID:26978357

  3. Stable overexpression of pregnane X receptor in HepG2 cells increases its potential for bioartificial liver application.

    PubMed

    Nibourg, Geert A A; Huisman, Maarten T; van der Hoeven, Tessa V; van Gulik, Thomas M; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

    2010-09-01

    To bridge patients with acute liver failure to transplantation or liver regeneration, a bioartificial liver (BAL) is urgently needed. A BAL consists of an extracorporeal bioreactor loaded with a bioactive mass that would preferably be of human origin and display high hepatic functionality, including detoxification. The human hepatoma cell line HepG2 exhibits many hepatic functions, but its detoxification function is low. In this study, we investigated whether stable overexpression of pregnane X receptor (PXR), a master regulator of diverse detoxification functions in the liver [eg, cytochrome P450 3A (CYP3A) activity], would increase the potential of HepG2 for BAL application. Stable overexpression was achieved by lentiviral expression of the human PXR gene, which yielded cell line cBAL119. In monolayer cultures of cBAL119 cells, PXR transcript levels increased 29-fold versus HepG2 cells. Upon activation of PXR by rifampicin, the messenger RNA levels of CYP3A4, CYP3A5, and CYP3A7 increased 49- to 213-fold versus HepG2 cells. According to reporter gene assays with different inducers, the highest increase in CYP3A4 promoter activity (131-fold) was observed upon induction with rifampicin. Inside BALs, the proliferation rates, as measured by the DNA content, were comparable between the 2 cell lines. The rate of testosterone 6beta-hydroxylation, a measure of CYP3A function inside BALs, increased 4-fold in cBAL119 BALs versus HepG2 BALs. Other functions, such as apolipoprotein A1 synthesis, urea synthesis, glucose consumption, and lactate production, remained unchanged or increased. Thus, stable PXR overexpression markedly increases the potential of HepG2 for BAL application. (c) 2010 AASLD.

  4. Increased Asthma Risk and Asthma-Related Health Care Complications Associated With Childhood Obesity

    PubMed Central

    Black, Mary Helen; Zhou, Hui; Takayanagi, Miwa; Jacobsen, Steven J.; Koebnick, Corinna

    2013-01-01

    Asthma is the most common chronic condition of childhood, yet the relationship between obesity and asthma risk and the impact of obesity on clinical asthma outcomes are not well understood. For this population-based, longitudinal study, demographic and clinical data were extracted from administrative and electronic health records of 623,358 patients aged 6–19 years who were enrolled in the Kaiser Permanente Southern California health plan in 2007–2011. Crude asthma incidence ranged from 16.9 per 1,000 person-years among normal-weight youth to 22.3 per 1,000 person-years among extremely obese youth. The adjusted risks of asthma for overweight, moderately obese, and extremely obese youth relative to those of normal weight youth were 1.16 (95% confidence interval: 1.13, 1.20), 1.23 (95% confidence interval: 1.19, 1.28), and 1.37 (95% confidence interval: 1.32, 1.42), respectively (Ptrend < 0.0001). The relationship between obesity and asthma risk was strongest in Asian/Pacific Islanders and in the youngest girls (aged 6–10 years), compared with other groups. Among youth who developed asthma, those who were moderately or extremely obese had more frequent asthma exacerbations requiring emergency department services and/or treatment with oral corticosteroids. In conclusion, obese youth are not only more likely to develop asthma, but they may be more likely to have severe asthma, resulting in a greater need for health care utilization and aggressive asthma treatment. PMID:23924576

  5. Dexamethasone increases UDP-glucuronyltransferase activity towards bilirubin, oestradiol and testosterone in foetal liver from rhesus monkey during late gestation.

    PubMed Central

    Leakey, J E; Althaus, Z R; Bailey, J R; Slikker, W

    1985-01-01

    We previously showed that in perinatal rhesus monkeys hepatic UDP-glucuronyltransferase activities appear to develop differentially in two clusters, analogous to those of the rat. We demonstrate here that hepatic UDP-glucuronyltransferase activities differ between the rat and the rhesus monkey in their response to glucocorticoids. Treatment of pregnant rhesus monkeys with dexamethasone during late gestation increases UDP-glucuronyltransferase activities towards bilirubin, oestradiol and testosterone in the foetal-liver microsomal fraction to 25, 4 and 4 times their low control values respectively. Analogous dexamethasone treatment in rat fails to increase these activities significantly in the foetal liver. These findings suggest that maternal glucocorticoid therapy in late gestation could greatly increase the newborn primate's capacity to glucuronidate bilirubin. PMID:3919703

  6. Role of IL28B genotype in the liver stiffness increase in untreated patients with chronic hepatitis C.

    PubMed

    Boglione, Lucio; Cusato, Jessica; Cariti, Giuseppe; Di Perri, Giovanni; D'Avolio, Antonio

    2017-09-01

    The role of interleukin (IL)28B has been deepened in the treatment response to pegylated-interferon in patients affected by chronic hepatitis C (CHC). However, recently the IL28B genotypes were also related to hepatic fibrosis progression in untreated patients, using the liver biopsy. The aim of this prospective and longitudinal study was to assess the role of different IL28B genotypes in the liver stiffness progression in a cohort of untreated subjects affected by CHC. We included in this analysis all untreated patients affected by CHC and followed for at least 5years with the annual evaluation of liver stiffness using Fibroscan®. All enrolled subjects were genotyped for rs8099917 and rs12979860 IL28B polymorphisms. In the study period, 266 patients were considered. After 5years we observed the following median stiffness increases: 6.7kPa [5.1-7.8] in TT/CC, 4.9kPa [4.1-5.0] in TT/TC, 3.4kPa [3.2-3.8] in TG/TC and 1.7kPa [1.2-1.9] in GG/TT. These values were statistically significant in all groups (p<0.001). In the multivariate analysis resulted as predictive factors of liver stiffness progression the following: IL28B TT/CC genotype (OR=4.571; 95%IC=2.381-12.994; p<0.001) and IL28B GG/TT genotype (OR=0.510; 95%IC=0.289-0.712; p=0.007). In this study we evidenced that IL28B genotypes were associated with a different level of liver stiffness increase after 5years and could be used to select the patients who should be treated with priority. Copyright © 2017. Published by Elsevier B.V.

  7. Monitoring of temperature increase and tissue vaporization during laser interstitial thermotherapy of ex vivo swine liver by computed tomography.

    PubMed

    Schena, E; Saccomandi, P; Giurazza, F; Del Vescovo, R; Mortato, L; Martino, M; Panzera, F; Di Matteo, F M; Beomonte Zobel, B; Silvestri, S

    2013-01-01

    Laser interstitial thermotherapy (LITT) is a minimally invasive technique used to thermally destroy tumour cells. Being based on hyperthermia, LITT outcome depends on the temperature distribution inside the tissue. Recently, CT scan thermometry, based on the dependence of the CT number (HU) on tissue temperature (T) has been introduced during LITT; it is an attractive approach to monitor T because it overcomes the concerns related to the invasiveness. We performed LITT on nine ex vivo swine livers at three different laser powers, (P=1.5 W, P=3 W, P=5 W) with a constant treatment time t=200 s; HU is averaged on two ellipsoidal regions of interest (ROI) of 0.2 cm2, placed at two distances from the applicator (d=3.6 mm and d=8.7 mm); a reference ROI was placed away from the applicator (d=30 mm). The aim of this study is twofold: 1) to evaluate the effect of the T increase in terms of HU variation in ex vivo swine livers undergoing LITT; and 2) to estimate the P value for tissue vaporization. To the best of our knowledge, this is the first study focused on the HU variation in swine livers undergoing LITT at different P. The reported findings could be useful to assess the effect of LITT on the liver in terms of both T changes and tissue vaporization, with the aim to obtain an effective therapy.

  8. Frailty is independently associated with increased hospitalisation days in patients on the liver transplant waitlist

    PubMed Central

    Sinclair, Marie; Poltavskiy, Eduard; Dodge, Jennifer L; Lai, Jennifer C

    2017-01-01

    AIM To investigate the impact of physical frailty on risk of hospitalisation in cirrhotic patients on the liver transplant waitlist. METHODS Cirrhotics listed for liver transplantation at a single centre underwent frailty assessments using the Fried Frailty Index, consisting of grip strength, gait speed, exhaustion, weight loss, and physical activity. Clinical and biochemical data including MELD score as collected at the time of assessment. The primary outcome was number of hospitalised days per year; secondary outcomes included incidence of infection. Univariable and multivariable analysis was performed using negative binomial regression to associate baseline parameters including frailty with clinical outcomes and estimated incidence rate ratios (IRR). RESULTS Of 587 cirrhotics, 64% were male, median age (interquartile range) was 60 (53-64) years and MELD score was 15 (12-18). Median Fried Frailty Index was 2 (1-3); 31.6% were classified as frail (fried frailty ≥ 3). During 12 mo of follow-up, 43% required at least 1 hospitalisation; 38% of which involved major infection. 107/184 (58%) frail and 142/399 (36%) non-frail patients were hospitalised at least once (P < 0.001). In univariable analysis, Fried Frailty Index was associated with total hospitalisation days per year (IRR = 1.51, 95%CI: 1.28-1.77; P ≤ 0.001), which remained significant on multivariable analysis after adjustment for MELD, albumin, and gender (IRR for frailty of 1.21, 95%CI: 1.02-1.44; P = 0.03). Incidence of infection was not influenced by frailty. CONCLUSION In cirrhotics on the liver transplant waitlist, physical frailty is a significant predictor of hospitalisation and total hospitalised days per year, independent of liver disease severity. PMID:28223735

  9. Progression from Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis Is Marked by a Higher Frequency of Th17 Cells in the Liver and an Increased Th17/Resting Regulatory T Cell Ratio in Peripheral Blood and in the Liver.

    PubMed

    Rau, Monika; Schilling, Anne-Kristin; Meertens, Jan; Hering, Ilona; Weiss, Johannes; Jurowich, Christian; Kudlich, Theodor; Hermanns, Heike M; Bantel, Heike; Beyersdorf, Niklas; Geier, Andreas

    2016-01-01

    Nonalcoholic fatty liver disease is increasing in prevalence. It can be subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Five to twenty percent of cases progress from NAFL to NASH. Increased hepatic Th17 cells and IL-17 expression were observed in NASH mice and patients, respectively. We analyzed CD4(+) effector T cells and regulatory T cells (Tregs) from peripheral blood and livers of NAFL and NASH patients. A total of 51 NAFL patients, 30 NASH patients, 31 nonalcoholic fatty liver disease patients (without histology), and 43 healthy controls were included. FACS analysis was performed on PBMCs and intrahepatic lymphocytes. Compared with healthy controls, a lower frequency of resting Tregs (rTregs; CD4(+)CD45RA(+)CD25(++)) and higher frequencies of IFN-γ(+) and/or IL-4(+) cells were detected among CD4(+) T cells of peripheral blood in NASH, and to a lesser degree in NAFL. In hepatic tissue, NAFL to NASH progression was marked by an increase in IL-17(+) cells among intrahepatic CD4(+) T cells. To define immunological parameters in peripheral blood to distinguish NAFL from NASH, we calculated different ratios. Th17/rTreg and Th2/rTreg ratios were significantly increased in NASH versus NAFL. The relevance of our findings for NASH pathogenesis was highlighted by the normalization of all of the changes 1 y after bariatric surgery. In conclusion, our data indicate that NAFL patients show changes in their immune cell profile compared with healthy controls. NAFL to NASH progression is marked by an increased frequency of IL-17(+) cells among intrahepatic CD4(+) T cells and higher Th17/rTreg and Th2/rTreg ratios in peripheral blood.

  10. Pretransplant Intra-arterial Liver-Directed Therapy Does Not Increase the Risk of Hepatic Arterial Complications in Liver Transplantation: A Single-Center 10-Year Experience.

    PubMed

    Kallini, Joseph R; Gabr, Ahmed; Ali, Rehan; Abouchaleh, Nadine; Riaz, Ahsun; Baker, Talia; Kulik, Laura; Caicedo, Juan; Salem, Riad; Lewandowski, Robert J

    2017-09-12

    To investigate the association between pretransplant intra-arterial liver-directed therapy (IAT) for hepatocellular carcinoma (HCC) and hepatic arterial complications (HAC) in orthotopic liver transplantation (OLT) [namely hepatic artery thrombosis (HAT) and/or the need for hepatic arterial conduit]. A total of 175 HCC patients (mean age: 60 years) underwent IAT with either transarterial chemoembolization or yttrium-90 (90Y) transarterial radioembolization prior to OLT between 2003 and 2013. A matched control cohort of 159 HCC patients who underwent OLT without prior IAT was selected. Incidence of HAC in both cohorts was investigated. The categorical differences between both cohorts were calculated by chi-square test. Among the 175 patients (chemoembolization, n = 82; radioembolization, n = 93), 8 (5%) required conduits due to HA disease (chemoembolization, n = 6; radioembolization, n = 2), 3 (2%) developed HAT (chemoembolization, n = 2; radioembolization, n = 1). Eleven of 175 patients (6.7%) had HAC. Of the 159 control patients, 6 (4%) needed conduits for HA disease and 3 (2%) developed HAT. Nine of 159 patients (5.7%) had HAC. Chi-square analysis between the IAT cohort and the control group yielded a p value of 0.810. When comparing chemoembolization to radioembolization, p = 0.076 (not significant at p < 0.05). Although aggressive pretransplant radioembolization and chemoembolization are both utilized in most liver transplant centers, neither appears to increase the risk of peri-transplant hepatic arterial complications in HCC patients.

  11. Kupffer cells-dependent inflammation in the injured liver increases recruitment of mesenchymal stem cells in aging mice

    PubMed Central

    Zong, Chen; Lai, Fobao; Zhu, Pengxi; Liu, Yu; Jiang, Jinghua; Yang, Yang; Gao, Lu; Ye, Fei; Zhao, Qiudong; Li, Rong; Han, Zhipeng; Wei, Lixin

    2016-01-01

    Mesenchymal stem cells (MSCs) repair tissue injury and may be used to treat immune associated diseases. In carbon tetrachloride (CCl4)-induced liver injury murine model, we administered MSCs. When MSCs were transmitted to young and old mice with liver injury, more MSCs were recruited in old mice. In old mice, inflammation, characterized by TNF-α and IL-6, was increased due to hyper-activation and hyper-function of Kupffer cells. Blocking Kupffer cells decreased MSCs migration in old mice. In vitro, Kupffer cells isolated from old mice secreted more inflammatory cytokines and chemokines. Thus, hyper-activation of Kupffer cells in old mice increased recruitment of MSCs after their therapeutic administration. PMID:26716516

  12. INCREASED RISK OF CHILDHOOD BRAIN TUMORS AMONG CHILDREN WHOSE PARENTS HAD FARM-RELATED PESTICIDE EXPOSURES DURING PREGNANCY.

    PubMed

    Kunkle, Brian; Bae, S; Singh, K P; Roy, D

    2014-11-01

    Malignant brain tumors rank second in both incidence and mortality by cancer in children, and they are the leading cause of cancer death in children. Relatively little is known about the etiology of childhood brain tumor (CBT). While there are several studies which link pesticide exposure to increased risk of CBT, findings have been inconsistent. We performed a meta-analysis on 15 published epidemiological studies to test that in utero exposure to pesticides may be involved in the development of brain cancer in children. Meta-analysis was performed using the general variance-based method and homogeneity was tested by means of the Q statistic. Summary relative risk (RR) estimates were calculated for childhood brain cancer from (1) paternal exposure to pesticides prior to conception, (2) both maternal and paternal exposure to pesticides during pregnancy, (3) maternal exposure during pregnancy to: (a) agricultural and (b) non-agricultural activities, and (4) childhood exposure to: (a) agricultural and (b) nonagricultural activities up to date of diagnosis with CBT. The comparative toxicogenomics database (CTD) was used to identify gene-pesticide-CBT interactions. Findings of meta-analyses revealed a significantly increased risk of CBT among children whose mothers had farm-related exposures during pregnancy (RR=1.48, 95% CI=1.18-1.84). A dose response was recognized when this risk estimate was compared to those for risk of CBT from maternal exposure to non-agricultural pesticides (e.g., home extermination, pest strips) during pregnancy (RR=1.36, 1.10-1.68), and risk of CBT among children exposed to agricultural activities (RR=1.32, 1.04-1.67). Three studies combined for the paternal exposure to pesticides during preconception produced a calculated summary risk estimate of odds ratio (OR) = 2.29 (95% CI: 1.39-3.78). Meta-analysis of five studies of paternal exposure to pesticides during pregnancy produced a final calculated summary risk estimate of OR = 1.63 (95% CI: 1

  13. INCREASED RISK OF CHILDHOOD BRAIN TUMORS AMONG CHILDREN WHOSE PARENTS HAD FARM-RELATED PESTICIDE EXPOSURES DURING PREGNANCY

    PubMed Central

    Kunkle, Brian; Bae, S.; Singh, K. P.; Roy, D.

    2015-01-01

    Malignant brain tumors rank second in both incidence and mortality by cancer in children, and they are the leading cause of cancer death in children. Relatively little is known about the etiology of childhood brain tumor (CBT). While there are several studies which link pesticide exposure to increased risk of CBT, findings have been inconsistent. We performed a meta-analysis on 15 published epidemiological studies to test that in utero exposure to pesticides may be involved in the development of brain cancer in children. Meta-analysis was performed using the general variance-based method and homogeneity was tested by means of the Q statistic. Summary relative risk (RR) estimates were calculated for childhood brain cancer from (1) paternal exposure to pesticides prior to conception, (2) both maternal and paternal exposure to pesticides during pregnancy, (3) maternal exposure during pregnancy to: (a) agricultural and (b) non-agricultural activities, and (4) childhood exposure to: (a) agricultural and (b) nonagricultural activities up to date of diagnosis with CBT. The comparative toxicogenomics database (CTD) was used to identify gene-pesticide-CBT interactions. Findings of meta-analyses revealed a significantly increased risk of CBT among children whose mothers had farm-related exposures during pregnancy (RR=1.48, 95% CI=1.18–1.84). A dose response was recognized when this risk estimate was compared to those for risk of CBT from maternal exposure to non-agricultural pesticides (e.g., home extermination, pest strips) during pregnancy (RR=1.36, 1.10–1.68), and risk of CBT among children exposed to agricultural activities (RR=1.32, 1.04–1.67). Three studies combined for the paternal exposure to pesticides during preconception produced a calculated summary risk estimate of odds ratio (OR) = 2.29 (95% CI: 1.39–3.78). Meta-analysis of five studies of paternal exposure to pesticides during pregnancy produced a final calculated summary risk estimate of OR = 1.63 (95

  14. Increased levels of rat liver RNA polymerase I(A) and I(B) following the administration of triiodothyronine.

    PubMed

    Zoncheddu, A; Accomando, R; Pertica, M; Carlini, A; Orunesu, M

    1981-06-15

    The levels of the transcribing RNA polymerase I(B) in the nucleus and of the non-transcribing RNA polymerase I(A) in the cytoplasm are both approximately doubled 24 h after a single i.p. injection of triiodothyronine into thyroidectomized rats. This suggests that the triiodothyronine-induced stimulation of ribosomal RNA synthesis is associated with an increase in the total RNA polymerase I content of rat liver cells.

  15. Childhood atopic dermatitis and warts are associated with increased risk of infection: a US population-based study.

    PubMed

    Silverberg, Jonathan I; Silverberg, Nanette B

    2014-04-01

    Previous studies suggested that atopic dermatitis (AD) is associated with aberrant immune responses, which might predispose toward both cutaneous and extracutaneous infections. The goal of this study was to determine whether childhood AD is associated with increased risk of warts, extracutaneous infections, and other atopic diseases and how these disorders cosegregate. The 2007 National Health Interview Survey from a nationally representative sample of 9417 children age 0 to 17 years was used. Children with AD and other atopic disease had higher odds of warts. In contrast, children with AD with or without other atopic disease had higher odds of extracutaneous infections, including strep throat, other sore throat, head or chest cold, influenza/pneumonia, sinus infections, recurrent ear infections, chickenpox, and urinary tract infections (P < .0001). Children with AD and other atopic disease had a higher number of infections than those with either disorder by itself (P < .0001). Warts were also associated with increased odds of all extracutaneous infections (P < .0001), except recurrent ear infections. Children with warts and AD had a higher number of infections than those with either disorder alone (P < .0001). Finally, children with AD and warts had higher odds of ever receiving a diagnosis of asthma, current asthma, asthma exacerbation in the past year, hay fever, and food allergy. Children with AD with warts had even higher odds of asthma, hay fever, and food allergies than those with AD and no warts. The associations between childhood AD, atopic disease, warts, and extracutaneous infections suggest that barrier disruption, immune disruption, or both contribute to susceptibility to warts and extracutaneous infections in children. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  16. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats

    PubMed Central

    Banerjee, Atrayee; Abdelmegeed, Mohamed A.; Jang, Sehwan; Song, Byoung-Joon

    2015-01-01

    The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT) or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH) (3.5 g/kg/dose oral gavages at 12-h intervals) or dextrose (Control). Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4), leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1) were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART), are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART. PMID:26484872

  17. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    PubMed

    Banerjee, Atrayee; Abdelmegeed, Mohamed A; Jang, Sehwan; Song, Byoung-Joon

    2015-01-01

    The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT) or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH) (3.5 g/kg/dose oral gavages at 12-h intervals) or dextrose (Control). Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4), leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1) were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART), are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  18. High Dietary Iron and Radiation Exposure Increase Biomarkers of Oxidative Stress in Blood and Liver of Rats

    NASA Technical Reports Server (NTRS)

    Morgan, Jennifer L. L.; Theriot, Corey A.; Wu, Honglu; Smith, Scott M.; Zwart, Sara R.

    2012-01-01

    Radiation exposure and increased iron (Fe) status independently cause oxidative damage that can result in protein, lipid, and DNA oxidation. During space flight astronauts are exposed to both increased radiation and increased Fe stores. Increased body Fe results from a decrease in red blood cell mass and the typically high Fe content of the food system. In this study we investigated the combined effects of radiation exposure (0.375 Gy of Cs-137 every other day for 16 days for a total of 3 Gy) and high dietary Fe (650 mg Fe/kg diet compared to 45 mg Fe/kg for controls) in Sprague-Dawley rats (n=8/group). Liver and serum Fe were significantly increased in the high dietary Fe groups. Likewise, radiation treatment increased serum ferritin and Fe concentrations. These data indicate that total body Fe stores increase with both radiation exposure and excess dietary Fe. Hematocrit decreased in the group exposed to radiation, providing a possible mechanism for the shift in Fe indices after radiation exposure. Markers of oxidative stress were also affected by both radiation and high dietary Fe, evidenced by increased liver glutathione peroxidase (GPX) and serum catalase as well as decreased serum GPX. We thus found preliminary indications of synergistic effects of radiation exposure and increased dietary Fe, warranting further study. This study was funded by the NASA Human Research Project.

  19. Increase of glycosaminoglycans and metalloproteinases 2 and 9 in liver extracellular matrix on early stages of extrahepatic cholestasis.

    PubMed

    Guedes, Pedro Luiz Rodrigues; Castañon, Maria Christina Marques Nogueira; Nagaoka, Márcia Regina; Aguiar, Jair Adriano Kopke de

    2014-01-01

    Cholestasis produces hepatocellular injury, leukocyte infiltration, ductular cells proliferation and fibrosis of liver parenchyma by extracellular matrix replacement. Analyze bile duct ligation effect upon glycosaminoglycans content and matrix metalloproteinase (MMPs) activities. Animals (6-8 weeks; n = 40) were euthanized 2, 7 or 14 days after bile duct ligation or Sham-surgery. Disease evolution was analyzed by body and liver weight, seric direct bilirubin, globulins, gamma glutamyl transpeptidase (GGT), alkaline phosphatase (Alk-P), alanine and aspartate aminotransferases (ALT and AST), tissue myeloperoxidase and MMP-9, pro MMP-2 and MMP-2 activities, histopathology and glycosaminoglycans content. Cholestasis caused cellular damage with elevation of globulins, GGT, Alk-P, ALT, AST. There was neutrophil infiltration observed by the increasing of myeloperoxidase activity on 7 (P = 0.0064) and 14 (P = 0.0002) groups which leads to the magnification of tissue injuries. Bile duct ligation increased pro-MMP-2 (P = 0.0667), MMP-2 (P = 0.0003) and MMP-9 (P<0.0001) activities on 14 days indicating matrix remodeling and establishment of inflammatory process. Bile duct ligation animals showed an increasing on dermatan sulfate and/or heparan sulfate content reflecting extracellular matrix production and growing mitosis due to parenchyma depletion. Cholestasis led to many changes on rats' liver parenchyma, as so as on its extracellular matrix, with major alterations on MMPs activities and glycosaminoglycans content.

  20. Increasing Choice or Inequality? Pathways through Early Education in Andhra Pradesh, India. Working Papers in Early Childhood Development, No. 58. Studies in Early Childhood Transitions

    ERIC Educational Resources Information Center

    Streuli, Natalia; Vennam, Uma; Woodhead, Martin

    2011-01-01

    This working paper is part of the Studies in Early Transitions series emerging from "Young Lives", a 15-year longitudinal study of childhood poverty in Ethiopia, India, Peru and Vietnam. It explores recent trends for children growing up in Andhra Pradesh, one of India's most populous states, based on Young Lives survey data collected for…

  1. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  2. Age-related consequences of childhood obesity.

    PubMed

    Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

    2014-01-01

    The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood.

  3. Hepatocyte X-box binding protein 1 deficiency increases liver injury in mice fed a high-fat/sugar diet.

    PubMed

    Liu, Xiaoying; Henkel, Anne S; LeCuyer, Brian E; Schipma, Matthew J; Anderson, Kristy A; Green, Richard M

    2015-12-15

    Fatty liver is associated with endoplasmic reticulum stress and activation of the hepatic unfolded protein response (UPR). Reduced hepatic expression of the UPR regulator X-box binding protein 1 spliced (XBP1s) is associated with human nonalcoholic steatohepatitis (NASH), and feeding mice a high-fat diet with fructose/sucrose causes progressive, fibrosing steatohepatitis. This study examines the role of XBP1 in nonalcoholic fatty liver injury and fatty acid-induced cell injury. Hepatocyte-specific Xbp1-deficient (Xbp1(-/-)) mice were fed a high-fat/sugar (HFS) diet for up to 16 wk. HFS-fed Xbp1(-/-) mice exhibited higher serum alanine aminotransferase levels compared with Xbp1(fl/fl) controls. RNA sequencing and Gene Ontogeny pathway analysis of hepatic mRNA revealed that apoptotic process, inflammatory response, and extracellular matrix structural constituent pathways had enhanced activation in HFS-fed Xbp1(-/-) mice. Liver histology demonstrated enhanced injury and fibrosis but less steatosis in the HFS-fed Xbp1(-/-) mice. Hepatic Col1a1 and Tgfβ1 gene expression, as well as Chop and phosphorylated JNK (p-JNK), were increased in Xbp1(-/-) compared with Xbp1(fl/fl) mice after HFS feeding. In vitro, stable XBP1-knockdown Huh7 cells (Huh7-KD) and scramble control cells (Huh7-SCR) were generated and treated with palmitic acid (PA) for 24 h. PA-treated Huh7-KD cells had increased cytotoxicity measured by lactate dehydrogenase release, apoptotic nuclei, and caspase3/7 activity assays compared with Huh7-SCR cells. CHOP and p-JNK expression was also increased in Huh7-KD cells following PA treatment. In conclusion, loss of XBP1 enhances injury in both in vivo and in vitro models of fatty liver injury. We speculate that hepatic XBP1 plays an important protective role in pathogenesis of NASH.

  4. CB1R antagonist increases hepatic insulin clearance in fat-fed dogs likely via upregulation of liver adiponectin receptors

    PubMed Central

    Iyer, Malini S.; Richey, Joyce M.; Woolcott, Orison O.; Asare Bediako, Isaac; Wu, Qiang; Kim, Stella P.; Stefanovski, Darko; Kolka, Cathryn M.; Hsu, Isabel R.; Catalano, Karyn J.; Chiu, Jenny D.; Ionut, Viorica; Bergman, Richard N.

    2015-01-01

    The improvement of hepatic insulin sensitivity by the cannabinoid receptor 1 (CB1R) antagonist rimonabant (RIM) has been recently been reported to be due to upregulation of adiponectin. Several studies demonstrated that improvement in insulin clearance accompanies the enhancement of hepatic insulin sensitivity. However, the effects of RIM on hepatic insulin clearance (HIC) have not been fully explored. The aim of this study was to explore the molecular mechanism(s) by which RIM affects HIC, specifically to determine whether upregulation of liver adiponectin receptors (ADRs) and other key genes regulated by adiponectin mediate the effects. To induce insulin resistance in skeletal muscle and liver, dogs were fed a hypercaloric high-fat diet (HFD) for 6 wk. Thereafter, while still maintained on a HFD, animals received RIM (HFD+RIM; n = 11) or placebo (HFD+PL; n = 9) for an additional 16 wk. HIC, calculated as the metabolic clearance rate (MCR), was estimated from the euglycemic-hyperinsulinemic clamp. The HFD+PL group showed a decrease in MCR; in contrast, the HFD+RIM group increased MCR. Consistently, the expression of genes involved in HIC, CEACAM-1 and IDE, as well as gene expression of liver ADRs, were increased in the HFD+RIM group, but not in the HFD+PL group. We also found a positive correlation between CEACAM-1 and the insulin-degrading enzyme IDE with ADRs. Interestingly, expression of liver genes regulated by adiponectin and involved in lipid oxidation were increased in the HFD+RIM group. We conclude that in fat-fed dogs RIM enhances HIC, which appears to be linked to an upregulation of the adiponectin pathway. PMID:26306598

  5. Colchicine reduces procollagen III and increases pseudocholinesterase in chronic liver disease

    PubMed Central

    Muntoni, Sergio; Rojkind, Marcos; Muntoni, Sandro

    2010-01-01

    AIM: To test whether colchicine would be an effective antifibrotic agent for treatment of chronic liver diseases in patients who could not be treated with α-interferon. METHODS: Seventy-four patients (46 males, 28 females) aged 40-66 years (mean 53 ± 13 years) participated in the study. The patients were affected by chronic liver diseases with cirrhosis which was proven histologically (n = 58); by chronic active hepatitis C (n = 4), chronic active hepatitis B (n = 2), and chronic persistent hepatitis C (n = 6). In the four patients lacking histology, cirrhosis was diagnosed from anamnesis, serum laboratory tests, esophageal varices and ascites. Patients were assigned to colchicine (1 mg/d) or standard treatment as control in a randomized, double-blind trial, and followed for 4.4 years with clinical and laboratory evaluation. RESULTS: Survival at the end of the study was 94.6% in the colchicine group and 78.4% in the control group (P = 0.001). Serum N-terminal peptide of type III procollagen levels fell from 34.0 to 18.3 ng/mL (P = 0.0001), and pseudocholinesterase levels rose from 4.900 to 5.610 mU/mL (P = 0.0001) in the colchicine group, while no significant change was seen in controls. Best results were obtained in patients with chronic hepatitis C and in alcoholic cirrhotics. CONCLUSION: Colchicine is an effective and safe antifibrotic drug for long-term treatment of chronic liver disease in which fibrosis progresses towards cirrhosis. PMID:20556834

  6. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

    PubMed

    Kunkel, Steven D; Elmore, Christopher J; Bongers, Kale S; Ebert, Scott M; Fox, Daniel K; Dyle, Michael C; Bullard, Steven A; Adams, Christopher M

    2012-01-01

    Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

  7. Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

    PubMed Central

    Kunkel, Steven D.; Elmore, Christopher J.; Bongers, Kale S.; Ebert, Scott M.; Fox, Daniel K.; Dyle, Michael C.; Bullard, Steven A.; Adams, Christopher M.

    2012-01-01

    Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness. PMID:22745735

  8. Pediatric nonalcoholic fatty liver disease.

    PubMed

    Bozic, Molly A; Subbarao, Girish; Molleston, Jean P

    2013-08-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the pediatric population. Increased recognition of this form of liver disease parallels the dramatic rise in childhood and adolescent obesity over the past 2 decades. Like adults, most children with NAFLD are obese, and comorbidities include insulin resistance, hypertension, and dyslipidemia. Unfortunately, pediatric NAFLD is not always a benign condition, with some children progressing to hepatic fibrosis and even cirrhosis in severe cases. The etiology of nonalcoholic steatohepatitis is not yet fully understood; however, hepatic steatosis in the context of insulin resistance and increased oxidative stress may lead to progressive disease. Although physical examination, laboratory evaluation, and radiographic findings provide clues to the potential presence of fatty liver disease, liver biopsy remains the gold standard for diagnosis. Lifestyle modification, including slow and steady weight loss, improved dietary habits, and increased daily, aerobic physical activity, remains the first-line approach in treating pediatric fatty liver disease. Antioxidant pharmacologic therapy such as use of vitamin E has shown some benefit in patients with biopsy-proven steatohepatitis. Nutrition plays an essential role not only in the development of fatty liver disease but also potentially in the treatment and prevention of progression to more severe disease.

  9. Liver Stiffness Values Are Lower in Pediatric Subjects than in Adults and Increase with Age: A Multifrequency MR Elastography Study.

    PubMed

    Etchell, Emily; Jugé, Lauriane; Hatt, Alice; Sinkus, Ralph; Bilston, Lynne E

    2017-04-01

    Purpose To determine if healthy hepatic mechanical properties differ between pediatric and adult subjects at magnetic resonance (MR) elastography. Materials and Methods Liver shear moduli in 24 healthy pediatric participants (13 children aged 5-14 years [seven boys, six girls] and 11 adolescents aged 15-18 years [six boys, five girls]) and 10 healthy adults (aged 22-36 years [five men, five women]) were obtained with 3-T MR elastography at 28, 56, and 84 Hz. Relationships between shear moduli and age were assessed with Spearman correlations. Differences between age groups were determined with one-way analysis of variance and Tukey multiple comparisons tests. Results Liver stiffness values (means ± standard deviations) were significantly lower in children and adolescents than in adults at 56 Hz (children, 2.2 kPa ± 0.3; adolescents, 2.2 kPa ± 0.2; adults, 2.6 kPa ± 0.3; analysis of variance, P = .009) and 84 Hz (children, 5.6 kPa ± 0.8; adolescents, 6.5 kPa ± 1.2; adults, 7.8 kPa ± 1.2; analysis of variance, P = .0003) but not at 28 Hz (children, 1.2 kPa ± 0.2; adolescents, 1.3 kPa ± 0.3; adults, 1.2 kPa ± 0.2; analysis of variance, P = .40). At 56 and 84 Hz, liver stiffness increased with age (Spearman correlation, r = 0.38 [P = .03] and r = 0.54 [P = .001], respectively). Stiffness varied less with frequency in children and adolescents than in adults (analysis of variance, P = .0009). No significant differences were found in shear moduli at 28, 56, or 84 Hz or frequency dependence between children and adolescents (P = .38, P = .99, P = .14, and P = .30, respectively, according to Tukey tests). Conclusion Liver stiffness values are lower and vary less with frequency in children and adolescents than in adults. Stiffness increases with age during normal development and approaches adult values during adolescence. Comparing pediatric liver stiffness to adult baseline values to detect pediatric liver mechanical abnormalities may not allow detection of mild

  10. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    PubMed

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-08-26

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

  11. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".

  12. A functional polymorphism of the NFKB1 gene increases the risk for alcoholic liver cirrhosis in patients with alcohol dependence.

    PubMed

    Marcos, Miguel; Pastor, Isabel; González-Sarmiento, Rogelio; Laso, Francisco Javier

    2009-11-01

    The genetic basis for the predisposition to alcoholic liver cirrhosis (ALC) remains unknown. Increasing evidence supports a role for the nuclear factor (NF)-kappaB, the NF-kappaB inhibitor alpha (NFKBIA), and the peroxisome proliferator-activated receptor (PPAR)-gamma in the pathogenesis of alcoholic liver disease, raising the possibility that common polymorphisms in genes encoding these molecules may confer susceptibility to ALC. The objective of this study was to analyze the relationship between common polymorphisms in NFKB1, NFKBIA, and PPARG2 genes and the presence of ALC. A total of 258 male alcoholics (161 without liver disease and 97 with ALC) and 101 healthy controls were genotyped for the -94ins/delATTG NFKB1, 3'-UTR+126G>A NFKBIA, and 34C>G PPARG2 polymorphisms. The association of these genetic variants with ALC was tested in alcoholic patients with alcohol abuse and alcohol dependence. A logistic regression analysis was further performed to analyze the model of inheritance. We found an association between the presence of the deletion allele in NFKB1 polymorphism and ALC in patients with alcohol dependence. We found no association between NFKBIA and PPARG2 polymorphisms and the presence of ALC. The deletion allele of the -94ins/del NFKB1 polymorphism could be associated with a higher risk of developing ALC through an increase in inflammation, as supported by previous data.

  13. Plasma levels of homocysteine and cysteine increased in pediatric NAFLD and strongly correlated with severity of liver damage.

    PubMed

    Pastore, Anna; Alisi, Anna; di Giovamberardino, Gianna; Crudele, Annalisa; Ceccarelli, Sara; Panera, Nadia; Dionisi-Vici, Carlo; Nobili, Valerio

    2014-11-17

    Non-alcoholic fatty liver disease (NAFLD) is a spectrum of metabolic abnormalities ranging from simple triglyceride accumulation in the hepatocytes to hepatic steatosis with inflammation, ballooning and fibrosis. It has been demonstrated that the pathogenesis of NAFLD involves increased oxidative stress, with consumption of the major cellular antioxidant, glutathione (GSH). Liver has a fundamental role in sulfur compound metabolism, although the data reported on plasma thiols status in NAFLD are conflicting. We recruited 63 NAFLD patients, and we analyzed all plasma thiols, such as homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CysGly) and GSH, by high-performance liquid chromatography (HPLC) with fluorescence detection. Hcy, Cys and CysGly plasma levels increased in NAFLD patients (p < 0.0001); whereas GSH levels were decreased in NAFLD patients when compared to controls (p < 0.0001). On the contrary, patients with steatohepatitis exhibited lower levels of Hcy and Cys than subjects without. Furthermore, a positive correlation was found between Hcy and Cys and the presence of fibrosis in children with NAFLD. Taken together, these data demonstrated a defective hepatic sulfur metabolism in children with NAFLD, and that high levels of Hcy and Cys probably correlates with a pattern of more severe histological liver damage, due to mechanisms that require further studies.

  14. Polyphenols decreased liver NADPH oxidase activity, increased muscle mitochondrial biogenesis and decreased gastrocnemius age-dependent autophagy in aged rats.

    PubMed

    Laurent, Caroline; Chabi, Beatrice; Fouret, Gilles; Py, Guillaume; Sairafi, Badie; Elong, Cecile; Gaillet, Sylvie; Cristol, Jean Paul; Coudray, Charles; Feillet-Coudray, Christine

    2012-09-01

    This study explored major systems of reactive oxygen species (ROS) production and their consequences on oxidative stress, mitochondriogenesis and muscle metabolism in aged rats, and evaluated the efficiency of 30-day oral supplementation with a moderate dose of a red grape polyphenol extract (RGPE) on these parameters. In the liver of aged rats, NADPH oxidase activity was increased and mitochondrial respiratory chain complex activities were altered, while xanthine oxidase activity remained unchanged. In muscles, only mitochondrial activity was modified with aging. The oral intake of RGPE decreased liver NADPH oxidase activity in the aged rats without affecting global oxidative stress, suggesting that NADPH oxidase was probably not the dominant detrimental source of production of O(2)·(-) in the liver. Interestingly, RGPE supplementation increased mitochondrial biogenesis and improved antioxidant status in the gastrocnemius of aged rats, while it had no significant effect in soleus. RGPE supplementation also decreased age-dependent autophagy in gastrocnemius of aged rats. These results extended existing findings on the beneficial effects of RGPE on mitochondriogenesis and muscle metabolism in aged rats.

  15. Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury.

    PubMed

    Grottke, Oliver; Braunschweig, Till; Spronk, Henri M H; Esch, Stephanie; Rieg, Annette D; van Oerle, Rene; ten Cate, Hugo; Fitzner, Christina; Tolba, Rene; Rossaint, Rolf

    2011-08-18

    Despite increasing use of prothrombin complex concentrate (PCC) to treat hemorrhage-associated coagulopathy, few studies have investigated PCC in trauma, and there is a particular lack of safety data. This study was performed to evaluate PCC therapy in a porcine model of coagulopathy with blunt liver injury. Coagulopathy was induced in 27 anesthetized pigs by replacing approximately 70% blood volume with hydroxyethyl starch 130/0.4 and Ringer's lactate solution; erythrocytes were collected and retransfused. Ten minutes after trauma, animals randomly received PCC (35 or 50 IU/kg) or saline. Coagulation parameters including thromboelastometry, thrombin generation, and blood loss were monitored for 2 hours. Internal organs were examined macroscopically and histologically to determine the presence of emboli and assess liver injury. Total blood loss was significantly lower and survival was higher in both PCC groups versus the control group (P < .05). These outcomes appeared to be dose-independent. Thromboembolism was found in all animals treated with 50 IU/kg PCC; 44% also showed signs of disseminated intravascular coagulation. Liver injury was similar in all animals. In conclusion, 35 IU/kg PCC safely improved coagulation and attenuated blood loss. However, the higher dose of PCC (50 IU/kg) appeared to increase the risk of thromboembolism and disseminated intravascular coagulation.

  16. Do naturally occurring magnetic nanoparticles in the human body mediate increased risk of childhood leukaemia with EMF exposure?

    PubMed

    Binhi, Vladimir

    2008-07-01

    To develop the hypothesis that magnetic nanoparticles, found in many organisms and often involved in biological reactions to weak electromagnetic fields (EMF), mediate EMF-induced DNA damage which could result in increased risk of childhood leukaemia and other cancers. An analysis of current research into magnetic nanoparticles. Physics estimates and the development of the hypothesis that intracellular magnetic nanoparticles chronically change the free radical concentration and can mediate the enhanced rate of DNA damage in hematopoietic stem cells. The properties of magnetic nanoparticles are considered and the naturally occurring magnetic field generated by a magnetic nanoparticle within a cell is calculated to be in the range of about 1-200 millitesla, which exceeds the level of the natural geomagnetic field by orders of magnitude. Experiments are summarized on the biological effects of static magnetic field in this range. It is shown that magnetic nanoparticles can increase the rate of free radical formation by a few percent, in the course of an idealized radical-pair reaction in a cell. A mechanism is discussed that explains how weak alternating magnetic fields, of the order of 0.4 muT, could cause an increase in the rate of leukaemia via millitesla fields produced around superparamagnetic nanoparticles in hematopoietic stem cells. The postulated presence of magnetic nanoparticles located in hematopoietic stem cells could constitute a cancer risk factor. Superparamagnetic nanoparticles can possibly mediate increased level of leukaemia caused by background exposure to low-frequency weak EMF.

  17. Childhood trauma is associated with increased brain responses to emotionally negative as compared with positive faces in patients with psychotic disorders.

    PubMed

    Aas, M; Kauppi, K; Brandt, C L; Tesli, M; Kaufmann, T; Steen, N E; Agartz, I; Westlye, L T; Andreassen, O A; Melle, I

    2017-03-01

    Childhood trauma increases risk of a range of mental disorders including psychosis. Whereas the mechanisms are unclear, previous evidence has implicated atypical processing of emotions among the core cognitive models, in particular suggesting altered attentional allocation towards negative stimuli and increased negativity bias. Here, we tested the association between childhood trauma and brain activation during emotional face processing in patients diagnosed with psychosis continuum disorders. In particular, we tested if childhood trauma was associated with the differentiation in brain responses between negative and positive face stimuli. We also tested if trauma was associated with emotional ratings of negative and positive faces. We included 101 patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM) schizophrenia spectrum or bipolar spectrum diagnosis. History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Brain activation was measured with functional magnetic resonance imaging during presentation of faces with negative or positive emotional expressions. After the scanner session, patients performed emotional ratings of the same faces. Higher levels of total childhood trauma were associated with stronger differentiation in brain responses to negative compared with positive faces in clusters comprising the right angular gyrus, supramarginal gyrus, middle temporal gyrus and the lateral occipital cortex (Cohen's d = 0.72-0.77). In patients with schizophrenia, childhood trauma was associated with reporting negative faces as more negative, and positive faces as less positive (Cohen's d > 0.8). Along with the observed negativity bias in the assessment of emotional valence of faces, our data suggest stronger differentiation in brain responses between negative and positive faces with higher levels of trauma.

  18. Acute treatment of constant darkness increases the efficiency of ATP synthase in rat liver mitochondria.

    PubMed

    Ramírez-Iñiguez, Ana Laura; Ortiz, Genaro Gabriel; El Hafidi, Mohammed; Rincón-Sánchez, Ana Rosa; Macías-Rodríguez, Ernesto; Pacheco-Moisés, Fermín Paul

    2009-01-01

    The circadian oscillations of many physiological processes provide an endogenous temporal program for the adaptive synchronization of mammals to the fluctuating external world. The lack of exposure to light causes the circadian system to undergo a process of dark adaptation similar to dark adaptation in the visual system. The aim of the present work was investigate the effect of acute treatment of constant darkness on mitochondrial ATP synthase activities and membrane fluidity in liver from male rat. We found that ATP synthase activity was not changed by the treatment. However ATPase activity and membrane fluidity were significantly diminished and pH gradient driven by ATP hydrolysis was incremented, in comparison from samples from rats kept on normal light/dark cycles. Additionally, the treatment of constant darkness diminishes the passive proton permeability of the inner mitochondrial membrane. In conclusion constant darkness induces a more efficient coupling between proton transport and catalysis, and increment the efficiency of the enzyme because the ratio of ATP synthase/ATPase activity was higher. These results exhibited the physiological adaptation of liver mitochondria to acute treatment of constant darkness in order to satisfy the cellular energy demand.

  19. Pyogenic liver abscesses associated with nonmetastatic colorectal cancers: An increasing problem in Eastern Asia

    PubMed Central

    Qu, Kai; Liu, Chang; Wang, Zhi-Xin; Tian, Feng; Wei, Ji-Chao; Tai, Ming-Hui; Zhou, Lei; Meng, Fan-Di; Wang, Rui-Tao; Xu, Xin-Sen

    2012-01-01

    AIM: To elaborate the clinicopathologic features of colorectal cancer-related pyogenic liver abscess (PLA). METHODS: Reported cases of colorectal cancer-related PLAs were collected from the literature published up to October 2011 and evaluated for their clinicopathologic features. Data of collected cases included demographics, clinical presentation, microbial findings and treatment. Categorical variables were compared by χ2 analysis and continuous variables were evaluated using Student’s t test. RESULTS: A total 96 cases of colorectal cancer-related PLA were collected from the previous literature. Most patients (60%) were male and 40% cases occurred in the age group of 61-70 years. Apart from some special types of PLA, there were significant differences in the microbiological spectrum between Eastern Asia and non-Eastern Asian countries, which implied different risk factors and courses of the disease. Gram negative bacteria especially Klebsiella pneumoniae (K. pneumoniae) PLA was predominant in Eastern Asia (80.0%) in contrast to non-Eastern Asian countries (P < 0.01). Meanwhile, most of the Eastern Asian patients exhibited smaller size of liver abscess and atypical presentation. Sigmoid colon and rectum (72.73%) were the main sites of tumor in Eastern Asian patients, whereas tumor sites were uneven among most of the non-Easter Asian PLA patients. CONCLUSION: K. pneumoniae PLA was strongly associated with colorectal cancer, especially those occurring in sigmoid colon and rectum, in elderly Eastern Asian male patients. PMID:22736918

  20. Can sorafenib increase survival for recurrent hepatocellular carcinoma after liver transplantation? A pilot study.

    PubMed

    Alsina, Angel E; Makris, Alexia; Nenos, Vasilios; Sucre, Eduardo; Arrobas, Jade; Franco, Edson; Kemmer, Nyingi

    2014-07-01

    Recurrence of hepatocellular carcinoma (HCC) remains a main detriment to long-term survival in liver transplants (LTx) for HCC. The study aims to review the use of sorafenib in recurrent HCC LTx in the Model End Stage Liver Disease era. Two hundred forty-seven patients with HCC LTx from 2002 to 2013 were included. Survival was calculated by the Kaplan-Meier (KM) method and Cox multivariate model. Twenty-two patients recurred (11%). By KM, overall survival was 27 months (standard deviation [SD], 3.2 months; median, 28.4 months). Mean time to recurrence was 16.9 months (SD, 2.8 months; median, 12 months). Nine patients were treated with sorafenib after recurrence. Median survival for sorafenib-treated patients was 42 months compared with a median of 16.2 months without sorafenib (-2 log likelihood ratio, P = 0.0582). By Cox, only sorafenib (P = 0.0233; hazard ratio, 8.528) and pathologic stage had a significant impact on survival. The recurrence rates of HCC LTx remain acceptable considering understaging and expansion of beyond Stage A. This pilot study of sorafenib in recurrent HCC demonstrates improved survival over historic controls. Many other factors affecting improved survival are explained. However, treatment remains palliative. Quality-of-life years and cost analysis need to be performed in this population.

  1. gamma-Glutamyl transpeptidase overexpression increases metastatic growth of B16 melanoma cells in the mouse liver.

    PubMed

    Obrador, Elena; Carretero, Julian; Ortega, Angel; Medina, Ignacio; Rodilla, Vicente; Pellicer, José A; Estrela, José M

    2002-01-01

    B16 melanoma (B16M) cells with high glutathione (GSH) content show rapid proliferation in vitro and high metastatic activity in the liver in vivo. gamma-Glutamyl transpeptidase (GGT)-mediated extracellular GSH cleavage and intracellular GSH synthesis were studied in vitro in B16M cells with high (F10) and low (F1) metastatic potential. GGT activity was modified by transfection with the human GGT gene (B16MF1/Tet-GGT cells) or by acivicin-induced inhibition. B16MF1/Tet-GGT and B16MF10 cells exhibited higher GSH content (35 +/- 6 and 40 +/- 5 nmol/10(6) cells, respectively) and GGT activity (89 +/- 9 and 37 +/- 7 mU/10(6) cells, respectively) as compared (P <.05) with B16MF1 cells (10 +/- 3 nmol GSH and 4 mU GGT/10(6) cells). Metastasis (number of foci/100 mm(3) of liver) increased in B16MF1 cells pretreated with GSH ester ( approximately 3-fold, P <.01), and decreased in B16MF1/Tet-GGT and B16MF10 cells pretreated with the GSH synthesis inhibitor L-buthionine (S,R)-sulphoximine ( approximately 5-fold and 2-fold, respectively, P <.01). Liver, kidney, brain, lung, and erythrocyte GSH content in B16MF1/Tet-GGT- or B16MF10-bearing mice decreased as compared with B16MF1- and non-tumor-bearing mice. Organic anion transporting polypeptide 1-independent sinusoidal GSH efflux from hepatocytes increased in B16MF1/Tet-GGT- or B16MF10-bearing mice ( approximately 2-fold, P <.01) as compared with non-tumor-bearing mice. Our results indicate that tumor GGT activity and an intertissue flow of GSH can regulate GSH content of melanoma cells and their metastatic growth in the liver.

  2. Hyperglycemia induces apoptosis in rat liver through the increase of hydroxyl radical: new insights into the insulin effect.

    PubMed

    Francés, Daniel E; Ronco, María T; Monti, Juan A; Ingaramo, Paola I; Pisani, Gerardo B; Parody, Juan P; Pellegrino, José M; Sanz, Paloma Martín; Carrillo, María C; Carnovale, Cristina E

    2010-05-01

    In this study, we analyzed the contribution of hydroxyl radical in the liver apoptosis mediated by hyperglycemia through the Bax-caspase pathway and the effects of insulin protection against the apoptosis induced by hyperglycemia. Male adult Wistar rats were randomized in three groups: control (C) (sodium citrate buffer, i.p.), streptozotocin (STZ)-induced diabetic (SID) (STZ 60 mg/kg body weight, i.p.), and insulin-treated SID (SID+I; 15 days post STZ injection, SID received insulin s.c., twice a day, 15 days). Rats were autopsied on day 30. In liver tissue, diabetes promoted a significant increase in hydroxyl radical production which correlated with lipid peroxidation (LPO) levels. Besides, hyperglycemia significantly increased mitochondrial BAX protein expression, cytosolic cytochrome c levels, and caspase-3 activity leading to an increase in apoptotic index. Interestingly, the treatment of diabetic rats with desferoxamine or tempol (antioxidants/hydroxyl radical scavengers) significantly attenuated the increase in both hydroxyl radical production and in LPO produced by hyperglycemia, preventing apoptosis by reduction of mitochondrial BAX and cytosolic cytochrome c levels. Insulin treatment showed similar results. The finding that co-administration of antioxidants/hydroxyl radical scavengers together with insulin did not provide any additional benefit compared with those obtained using either inhibitors or insulin alone shows that it is likely that insulin prevents oxidative stress by reducing the effects of hydroxyl radicals. Importantly, insulin significantly increased apoptosis inhibitor protein expression by induction of its mRNA. Taken together, our studies support that, at least in part, the hydroxyl radical acts as a reactive intermediate, which leads to liver apoptosis in a model of STZ-mediated hyperglycemia. A new anti-apoptosis signal for insulin is shown, given by an increase of apoptosis inhibitor protein.

  3. Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver.

    PubMed

    Mikula, Michal; Majewska, Aneta; Ledwon, Joanna Karolina; Dzwonek, Artur; Ostrowski, Jerzy

    2014-12-01

    Obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; also known as Ccl2). However, the chromatin make-up at these genes in the liver in obese individuals has not been explored. In this study, to identify obesity-mediated epigenetic changes at Tnfa and Ccl2, we used a murine model of obesity induced by a high-fat diet (HFD) and hyperphagic (ob/ob) mice. Chromatin immunoprecipitation (ChIP) assay was used to determine the abundance of permissive histone marks, namely histone H3 lysine 9 and 18 acetylation (H3K9/K18Ac), H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 36 trimethylation (H3K36me3), in conjunction with polymerase 2 RNA (Pol2) and nuclear factor (Nf)-κB recruitment in the liver. Additionally, to correlate the liver tissue-derived ChIP measurements with a robust in vitro transcriptional response at the Tnfa and Ccl2 genes, we used lipopolysaccharide (LPS) treatment to induce an inflammatory response in Hepa1-6 cells, a cell line derived from murine hepatocytes. ChIP revealed increased H3K9/K18Ac at Tnfa and Ccl2 in the obese mice, although the differences were only statistically significant for Tnfa (p<0.05). Unexpectedly, the levels of H3K4me3 and H3K36me3 marks, as well as Pol2 and Nf-κB recruitment, did not correspond with the increased expression of these two genes in the obese mice. By contrast, the acute treatment of Hepa1-6 cells with LPS significantly increased the H3K9/K18Ac marks, as well as Pol2 and Nf-κB recruitment at both genes, while the levels of H3K4me3 and H3K36me3 marks remained unaltered. These results demonstrate that increased Tnfa and Ccl2 expression in fatty liver at the chromatin level corresponds to changes in the level of histone H3 acetylation.

  4. Adverse childhood experiences and behavioral problems in middle childhood.

    PubMed

    Hunt, Tenah K A; Slack, Kristen S; Berger, Lawrence M

    2016-11-21

    Children who have been exposed to maltreatment and other adverse childhood experiences (ACEs) are at increased risk for various negative adult health outcomes, including cancer, liver disease, substance abuse, and depression. However, the proximal associations between ACEs and behavioral outcomes during the middle childhood years have been understudied. In addition, many of the ACE studies contain methodological limitations such as reliance on retrospective reports and limited generalizability to populations of lower socioeconomic advantage. The current study uses data from the Fragile Families and Child Wellbeing Study, a national urban birth cohort, to prospectively assess the adverse experiences and subsequent behavior problems of over 3000 children. Eight ACE categories to which a child was exposed by age 5 were investigated: childhood abuse (emotional and physical), neglect (emotional and physical), and parental domestic violence, anxiety or depression, substance abuse, or incarceration. Results from bivariate analyses indicated that Black children and children with mothers of low education were particularly likely to have been exposed to multiple ACE categories. Regression analyses showed that exposure to ACEs is strongly associated with externalizing and internalizing behaviors and likelihood of ADHD diagnosis in middle childhood. Variation in these associations by racial/ethnic, gender, and maternal education subgroups are examined. This study provides evidence that children as young as 9 begin to show behavioral problems after exposure to early childhood adversities.

  5. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

    USDA-ARS?s Scientific Manuscript database

    Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hypergl...

  6. Increased whole-body adiposity without a concomitant increase in liver fat is not associated with augmented metabolic dysfunction.

    PubMed

    Magkos, Faidon; Fabbrini, Elisa; Mohammed, B Selma; Patterson, Bruce W; Klein, Samuel

    2010-08-01

    Aim of this study was to determine whether an increase in adiposity, without a concomitant increase in intrahepatic triglyceride (IHTG) content, is associated with a deterioration in metabolic function. To this end, multiorgan insulin sensitivity, assessed by using a two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusion, and very low-density lipoprotein (VLDL) kinetics, assessed by using stable isotopically labeled tracer infusion and mathematical modeling, were determined in 10 subjects with class I obesity (BMI: 31.6 +/- 0.3 kg/m(2); 37 +/- 2% body fat; visceral adipose tissue (VAT): 1,225 +/- 144 cm(3)) and 10 subjects with class III obesity (BMI: 41.5 +/- 0.5 kg/m(2); 43 +/- 2% body fat; VAT: 2,121 +/- 378 cm(3)), matched on age, sex, and IHTG content (14 +/- 4 and 14 +/- 3%, respectively). No differences between class I and class III obese groups were detected in insulin-mediated suppression of palmitate (67 +/- 3 and 65 +/- 3%, respectively; P = 0.635) and glucose (67 +/- 3 and 73 +/- 5%, respectively; P = 0.348) rates of appearance in plasma, and the insulin-mediated increase in glucose disposal (218 +/- 18 and 193 +/- 30%, respectively; P = 0.489). In addition, no differences between class I and class III obese groups were detected in secretion rates of VLDL-triglyceride (6.5 +/- 1.0 and 6.0 +/- 1.4 micromol/l x min, respectively; P = 0.787) and VLDL-apolipoprotein B-100 (0.40 +/- 0.05 and 0.41 +/- 0.04 nmol/l x min, respectively; P = 0.866), and plasma clearance rates of VLDL-triglyceride (31 (16-59) and 29 (18-46) ml/min, respectively; P = 0.888) and VLDL-apolipoprotein B-100 (15 (11-19) and 17 (11-25) ml/min, respectively; P = 0.608). We conclude that increased adiposity without a concomitant increase in IHTG content does not cause additional abnormalities in adipose tissue, skeletal muscle, and hepatic insulin sensitivity, or VLDL metabolism.

  7. Levels of somatic hypermutations in B cell receptors increase during childhood

    PubMed Central

    Schatorjé, E J H; Driessen, G J; van Hout, R W N M; van der Burg, M; de Vries, E

    2014-01-01

    Somatic hypermutation (SHM) is an important step in antigen-driven B cell development creating B lymphocytes expressing high-affinity antibody receptors. It is known that the peripheral B lymphocyte compartments of healthy children and adults differ considerably. However, the development of SHM with age has not been studied in detail previously. Therefore, we used the immunoglobulin (Ig)κ-restriction enzyme hot-spot mutation assay (Igκ-REHMA) to gain an estimation of SHM levels in different age groups in order to relate this to the size of the memory B lymphocyte subpopulations. We show that the level of SHM increases rapidly during the first 2 years of life. This reflects the changes of the memory B cell subpopulations, but also changes in the SHM within memory B cell subsets, probably reflecting an increase of secondary memory B cell responses. PMID:25039369

  8. Increased erythrocyte protoporphyrins and blood lead - a pilot study of childhood growth patterns

    SciTech Connect

    Angle, C.R.; Kuntzelman, D.R. )

    1989-01-01

    The National Health and Nutrition Survey 1976-1980 demonstrated the inverse association of blood lead 8-35 {mu}g/dl (0.4-1.7 {mu}M) with height and weight in 2680 children 1-7 yr old. Growth has not been examined. A retrospective pilot study was made of growth, 0-42 mo, for 54 children found to have erythrocyte protoporphyrins >35 {mu}g/dl (0.6 mM) at 12-23 mo. For 24/54, all blood leads were <30 {mu}g/dl (1.2 {mu}M), with a peak annual mean of 18.5 {mu}g/dl (0.9 {mu}M); for 30/54, mean blood lead was 46.7 {mu}/dl (2.2 {mu}M) at 12-23 mo with all subsequent blood leads {ge}30 {mu}g/dl (1.2 {mu}M). In both groups the mean height and weight at birth were at the 25th percentile. The high-lead children had increased weight velocity at 15 mo of age and were heavier at 24 mo. Weight gain related to total caloric intake, supporting food consumption, and hand-to-mouth behavior as significant factors in an increased blood lead ages 9-24 mo. The monthly directional change of height and weight percentiles after 24 mo, however, showed a decreased frequency of upward shifts when blood lead was {ge}30 {mu}g/dl. Although an early high food intake appears to contribute to high blood lead by increasing the intake of lead from food and mouthing, persistent increases in the high blood lead and erythrocyte protoporphyrins were associated with subsequent growth retardation.

  9. Increasing incidence of childhood celiac disease in Sicily: results of a multicenter study.

    PubMed

    Magazzú, G; Bottaro, G; Cataldo, F; Iacono, G; Di Donato, F; Patane, R; Cavataio, F; Maltese, I; Romano, C; Arco, A

    1994-10-01

    By screening the patient list of four Sicilian centers of gastroenterology and those with gluten-free product consumption, 1074 patients (607 females and 467 males) with celiac disease, diagnosed between 1975 and 1989, were identified. A maximum cumulative incidence rate by birth cohort was reached in 1986 (1.65/1000). When the incidence rate was adjusted for the years of follow-up, the actual standardized rate was 3 cases per 1000 live births. Growth failure and chronic diarrhea were the most common symptoms, but a diminishing trend for chronic diarrhea was observed when symptoms were distributed by year of diagnosis. Even though 61.1% of all cases were diagnosed within six months from the onset of symptoms, mean age at diagnosis showed an increasing trend, from less than two years to approximately four years of age. The results of our study showed an increasing incidence of celiac disease due to diagnosis of less typical cases at an older age and also to a steady increase in the rate of diagnosis of cases with a classic clinical picture.

  10. Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice.

    PubMed

    Kim, In Hee; Xu, Jun; Liu, Xiao; Koyama, Yukinori; Ma, Hsiao-Yen; Diggle, Karin; You, Young-Hyun; Schilling, Jan M; Jeste, Dilip; Sharma, Kumar; Brenner, David A; Kisseleva, Tatiana

    2016-08-01

    We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between old-aged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or

  11. Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease.

    PubMed

    Castiella, Agustin; Zapata, Eva; Lucena, M Isabel; Andrade, Raúl J

    2014-04-27

    The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease.

  12. Increased childhood mortality and arsenic in drinking water in Matlab, Bangladesh: a population-based cohort study.

    PubMed

    Rahman, Mahfuzar; Sohel, Nazmul; Yunus, Mohammad; Chowdhury, Mahbub Elahi; Hore, Samar Kumar; Zaman, Khalequ; Bhuiya, Abbas; Streatfield, Peter Kim

    2013-01-01

    Arsenic in drinking water was associated with increased risk of all-cause, cancer, and cardiovascular death in adults. However, the extent to which exposure is related to all-cause and deaths from cancer and cardiovascular condition in young age is unknown. Therefore, we prospectively assessed whether long-term and recent arsenic exposures are associated with all-cause and cancer and cardiovascular mortalities in Bangladeshi childhood population. We assembled a cohort of 58406 children aged 5-18 years from the Health and Demographic Surveillance System of icddrb in Bangladesh and followed during 2003-2010. There were 185 non-accidental deaths registered in-about 0.4 million person-years of observation. We calculated hazard ratios for cause-specific death in relation to exposure at baseline (µg/L), time-weighted lifetime average (µg/L) and cumulative concentration (µg-years/L). After adjusting covariates, hazard ratios (HRs) for all-cause childhood deaths comparing lifetime average exposure 10-50.0, 50.1-150.0, 150.1-300.0 and ≥300.1µg/L were 1.37 (95% confidence interval [CI], 0.74-2.57), 1.44 (95% CI, 0.88-2.38), 1.22 (95% CI, 0.75-1.98) and 1.88 (95% CI, 1.14-3.10) respectively. Significant increased risk was also observed for baseline (P for trend = 0.023) and cumulative exposure categories (P for trend = 0.036). Girls had higher mortality risk compared to boys (HR for girls 1.79, 1.21, 1.64, 2.31; HR for boys 0.52, 0.53, 1.14, 0.99) in relation to baseline exposure. For all cancers and cardiovascular deaths combined, multivariable adjusted HRs amounted to 1.53 (95% CI 0.51-4.57); 1.29 (95% CI 0.43-3.87); 2.18 (95%CI 1.15-4.16) for 10.0-50.0, 50.1-150.0, and ≥150.1, comparing lowest exposure as reference (P for trend = 0.009). Adolescents had higher mortality risk compared to children (HRs = 1.53, 95% CI 1.03-2.28 vs. HRs = 1.30, 95% CI 0.78-2.17). Arsenic exposure was associated with substantial increased risk of deaths at young age

  13. Increased Incidence and Clinical Picture of Childhood Narcolepsy following the 2009 H1N1 Pandemic Vaccination Campaign in Finland

    PubMed Central

    Partinen, Markku; Saarenpää-Heikkilä, Outi; Ilveskoski, Ismo; Hublin, Christer; Linna, Miika; Olsén, Päivi; Nokelainen, Pekka; Alén, Reija; Wallden, Tiina; Espo, Merimaaria; Rusanen, Harri; Olme, Jan; Sätilä, Heli; Arikka, Harri; Kaipainen, Pekka; Julkunen, Ilkka; Kirjavainen, Turkka

    2012-01-01

    Background Narcolepsy is a rare neurological sleep disorder especially in children who are younger than 10 years. In the beginning of 2010, an exceptionally large number of Finnish children suffered from an abrupt onset of excessive daytime sleepiness (EDS) and cataplexy. Therefore, we carried out a systematic analysis of the incidence of narcolepsy in Finland between the years 2002–2010. Methods All Finnish hospitals and sleep clinics were contacted to find out the incidence of narcolepsy in 2010. The national hospital discharge register from 2002 to 2009 was used as a reference. Findings Altogether 335 cases (all ages) of narcolepsy were diagnosed in Finland during 2002–2009 giving an annual incidence of 0.79 per 100 000 inhabitants (95% confidence interval 0.62–0.96). The average annual incidence among subjects under 17 years of age was 0.31 (0.12–0.51) per 100 000 inhabitants. In 2010, 54 children under age 17 were diagnosed with narcolepsy (5.3/100 000; 17-fold increase). Among adults ≥20 years of age the incidence rate in 2010 was 0.87/100 000, which equals that in 2002–2009. Thirty-four of the 54 children were HLA-typed, and they were all positive for narcolepsy risk allele DQB1*0602/DRB1*15. 50/54 children had received Pandemrix vaccination 0 to 242 days (median 42) before onset. All 50 had EDS with abnormal multiple sleep latency test (sleep latency <8 min and ≥2 sleep onset REM periods). The symptoms started abruptly. Forty-seven (94%) had cataplexy, which started at the same time or soon after the onset of EDS. Psychiatric symptoms were common. Otherwise the clinical picture was similar to that described in childhood narcolepsy. Interpretation A sudden increase in the incidence of abrupt childhood narcolepsy was observed in Finland in 2010. We consider it likely that Pandemrix vaccination contributed, perhaps together with other environmental factors, to this increase in genetically susceptible children. PMID:22470463

  14. Intergenerational violence in Burundi: Experienced childhood maltreatment increases the risk of abusive child rearing and intimate partner violence.

    PubMed

    Crombach, Anselm; Bambonyé, Manassé

    2015-01-01

    Experiencing abuse during childhood affects the psychological well-being of individuals throughout their lives and may even influence their offspring by enhancing the likelihood of an intergenerational transmission of violence. Understanding the effects of childhood maltreatment on child-rearing practices and intimate partner violence might be of particular importance to overcome the consequences of violent conflicts in African societies. Using Burundi as an example, we aimed to explore the associations between childhood maltreatment, intimate partner violence, perceived partner intimidation, gender and the probability of violently acting out against one's own children or romantic partner. Amongst a sample of 141 men and 141 women in the capital of Burundi, we identified those who had biological children and those who lived or had lived in relationships. Using culturally appropriate instruments, we enquired about their exposure to childhood maltreatment and partner violence as well as their inclinations to act out violently. We found that childhood maltreatment and perceived partner intimidation were strong predictors for the perpetration of violence against children. Moreover, we found that women were more likely to use violence against children if they experienced partner violence and less likely to resort to violence if they felt intimidated. Men were more likely to perpetrate violence against their partner. Childhood maltreatment was again a strong predictor. The more women experienced partner violence, the more they fought back. Childhood maltreatment is a strong predictor for domestic violence and has to be addressed to interrupt the cycle of violence in post-conflict countries.

  15. [Family history of liver cancer increases the risk of liver cancer incidence: a 20-year prospective cohort study in Qidong, China].

    PubMed

    Sun, Yan; Tu, Hong; Lu, Peixin; Wang, Jinbing; Wu, Yan; Zhang, Qinan; Qian, Gengsun; Chen, Taoyang

    2014-10-01

    To evaluate whether first-degree family history of liver cancer plays a role in liver cancer incidence by prospective evaluation of a patient cohort in Qidong, China over a 20-year period. In May 1992, 708 hepatitis B surface antigen (HBsAg) carriers and 730 HBsAg-negadve controls from Qidong city were enrolled for participation in a prospective cohort study ending in November 2012.Follow-up was carried out every 6 to 12 months, and evaluations included serum assays to measure concentrations of alpha fetoprotein (AFP), HBsAg and alanine aminotransferase (ALT), as well as abdominal ultrasound to assess liver disease.The relationship between baseline (study entry) information of patients with first-degree family history of liver cancer and liver cancer incidence during the two decades of study was statistically assessed. There were 172 newly diagnosed liver cancer cases in the cohort during 25 753 person-years (py) of follow-up, representing an incidence of 667.88/100 000 py.The incidence rates of liver cancer among participants with or without liver cancer family history were 1 244.36/100 000 py and 509.70/100 000 py respectively, and the between-group difference reached the threshold for statistical significance (P less than 0.01, Relative Risk (RR):2.44, 95% Confidence Interval (CI):1.80-3.31).The incidence rates of liver cancer among participants who had a sibling with liver cancer and participants who had a parent with liver cancer were not significantly different (P > 0.05), but the liver cancer incidence among participants who had a mother with liver cancer was significantly higher than that of participants who had a father with liver cancer (P < 0.05, RR:1.86, 95% CI:1.03-3.36). Among the participants with liver cancer family history, 56.52% (39/69) were diagnosed before 50 years old, and this rate was significantly higher than that of participants without a family history of liver cancer (40.78%, 42/103, P less than 0.05).The incidence rate of liver cancer

  16. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication.

    PubMed

    Atkinson, Helen C; Marsh, Julie A; Rath, Shoshana R; Kotecha, Rishi S; Gough, Hazel; Taylor, Mandy; Walwyn, Thomas; Gottardo, Nicholas G; Cole, Catherine H; Choong, Catherine S

    2015-01-01

    Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P < 0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P = 0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P = 0.0005), disease risk (P < 0.0001), age (P = 0.0001), and BMI z-score (P < 0.0001) at diagnosis and total dose of steroid during maintenance (P = 0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.

  17. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication

    PubMed Central

    Atkinson, Helen C.; Marsh, Julie A.; Rath, Shoshana R.; Kotecha, Rishi S.; Gottardo, Nicholas G.; Cole, Catherine H.; Choong, Catherine S.

    2015-01-01

    Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P < 0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P = 0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P = 0.0005), disease risk (P < 0.0001), age (P = 0.0001), and BMI z-score (P < 0.0001) at diagnosis and total dose of steroid during maintenance (P = 0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL. PMID:26101530

  18. A High-Fat, High-Fructose Diet Induces Antioxidant Imbalance and Increases the Risk and Progression of Nonalcoholic Fatty Liver Disease in Mice

    PubMed Central

    Jearapong, Nattharat; Pimson, Charinya; Chatuphonprasert, Waranya

    2016-01-01

    Excessive fat liver is an important manifestation of nonalcoholic fatty liver disease (NAFLD), associated with obesity, insulin resistance, and oxidative stress. In the present study, the effects of a high-fat, high-fructose diet (HFFD) on mRNA levels and activities of the antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were determined in mouse livers and brains. The histomorphology of the livers was examined and the state of nonenzymatic reducing system was evaluated by measuring the glutathione system and the lipid peroxidation. Histopathology of the liver showed that fat accumulation and inflammation depended on the period of the HFFD-consumption. The levels of mRNA and enzymatic activities of SOD, CAT, and GPx were raised, followed by the increases in malondialdehyde levels in livers and brains of the HFFD mice. The oxidized GSSG content was increased while the total GSH and the reduced GSH were decreased, resulting in the increase in the GSH/GSSG ratio in both livers and brains of the HFFD mice. These observations suggested that liver damage and oxidative stress in the significant organs were generated by continuous HFFD-consumption. Imbalance of antioxidant condition induced by long-term HFFD-consumption might increase the risk and progression of NAFLD. PMID:27019761

  19. Increased T-cell sinusoidal lymphocytosis in liver biopsies in patients with chronic hepatitis C and mixed cryoglobulinemia.

    PubMed

    Carmack, Susanne; Taddei, Tamar; Robert, Marie E; Mistry, Pramod; Jain, Dhanpat

    2008-03-01

    Mixed cryoglobulinemia (MC) has a strong association with hepatitis C virus (HCV) infection and is associated with a higher degree of fibrosis and poor response to therapy. Currently, there are no known histological findings on liver biopsy that correlate with the presence of MC in HCV-infected patients, although we have occasionally noted prominent sinusoidal lymphocytosis in MC patients. The goal of this study is to determine whether sinusoidal lymphocytosis is a histological marker of MC in liver biopsies from patients with chronic hepatitis C. The liver clinic database at our institution was searched for chronic hepatitis C patients with MC who underwent liver biopsy during 1999-2005. Ten such cases were identified and were included in the study. Ten chronic hepatitis C MC-negative cases were matched for age and stage of fibrosis to serve as controls. Histological features (sinusoidal lymphocytes, inflammatory activity, acidophil bodies, and fibrosis stage) were evaluated in each biopsy. Clinical and laboratory data (serum protein electrophoresis, liver enzymes, hepatitis C viral load, treatment status, comorbidities, etc.) were also recorded. Formalin-fixed, paraffin-embedded sections were submitted for immunohistochemical analysis using antibodies against CD3, CD20, CD4, CD8, and CD68. Sinusoidal lymphocytes were counted in 5 hpf (40x) on hematoxylin and eosin (H&E) stain, and on CD3 and CD20 immunostains. The number of CD68+ Kupffer cells was also counted in a similar fashion. In the MC-positive versus MC-negative cases, mean fibrosis stage (2.4 vs. 2.4), inflammatory grade (1.7 vs. 2.1), lymphocyte count (359 vs. 128/5 hpf), and Kupffer cell count (239 vs. 220/5 HPF) were assessed. There was a significant increase in sinusoidal T-cell lymphocytes (P < 0.05) in MC-positive cases as compared to MC-negative cases. Nearly all sinusoidal lymphocytes were CD8-positive cells in both groups. Other histological parameters did not differ in the two groups. MC

  20. Increasing burden of childhood severe malaria in a Nigerian tertiary hospital: implication for control.

    PubMed

    Orimadegun, Adebola Emmanuel; Fawole, Olufunmi; Okereke, James Okorie; Akinbami, Felix Olukayode; Sodeinde, Olugbemiro

    2007-06-01

    Malaria remains an important public heath concern in Nigeria because of its impact on child and maternal health, but the contribution of severe malaria to morbidity among Nigerian children was scantly reported. This study was undertaking to document the hospital-burden of severe malaria among children in Ibadan in order to reflect on the impacts and health implications of the current malaria control strategies. A review of 6-year case records of all children admitted to the emergency ward of the University College Hospital Ibadan was carried out. Cases of severe malaria were defined as those children in whom parasitaemia were confirmed with blood film microscopy and any of the WHO case definitions for severe malaria was documented. Severe malaria cases constituted 11.3% of 16 031 admissions (2000-05) with 89.1% being children <5 years old. Cerebral malaria accounted for about one-fifth (19.7%) of all severe malaria cases. The yearly proportional morbidity rate from severe malaria ranged from 8.7% to 13.2% with significant increase from 2000 to 2004 (X2 = 48.49; df = 5; P < 0.001). Severe malaria accounted for 12.4% of all paediatric deaths with an estimated overall case fatality rate of 9.6%. Deaths from malaria were significantly associated with wasting (Z-score for weight-for-height increased trend in morbidity from severe malaria over the study period. Severe malarial anaemia was a more common complication of Plasmodium falciparum malaria than cerebral malaria in hospitalized Nigerian children and it was associated with a high number of deaths. The consequences of high rate of severe malaria may be beyond health as it also affects the economy and the developmental prospects of the country. There may therefore a need to review the current strategies for malaria control in Nigeria.

  1. Increasing incidence of childhood type 1 diabetes in Montenegro from 1997 to 2006.

    PubMed

    Samardzic, Mira; Marinkovic, Jelena; Kocev, Nikola; Curovic, Natasa; Terzic, Natasa

    2010-09-01

    To determine and analyze the incidence of type 1 diabetes mellitus (T1DM) in 0- to 14-yr-old children in Montenegro from 1997 to 2006. This was a prospective study. Primary case ascertainment came from a diabetes register and secondary independent data source was from prescription data. Age and sex-standardized incidence rates were calculated using direct method, assuming an equal distribution in each age/sex group. The 95% confidence interval (CI) were estimated assuming the Poisson distribution. The independent effects of calendar year, two 5-yr time periods, sex and age groups were estimated with Poisson regression modeling. During the 10-yr period, 184 new cases of type 1 diabetes were identified. Case ascertainment was 100% complete using the capture-recapture method. The mean annual standardized incidence rate over the 10-yr period was 13.4/100 000/yr (95% CI: 11.5-15.5). It increased on average by 4.6% per year (95% CI: -0.4 to -9.6%, p = 0.07). The time-period specific incidence rate from year 1997 to 2001 was significantly lower (10.8; 8.5-13.5) compared with the second period from 2002 to 2006 (16.3; 13.3-19.7), (p < 0.0001). The age-specific incidence for the 0-4-yr age group was significantly lower (8.9; 6.3-12.3) than in 5- to 9-yr age group (14.1; 10.8-18.1); and in the 10-14 yr group (17.2; 13.7-21.3) per 100,000 children. The incidence rate in last 5 yr places Montenegro in the group of countries with moderate risk for development of type 1 diabetes in children. The average annual increase in incidence is 4.6%.

  2. From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease.

    PubMed

    Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia Del Giudice, Emanuele; Santoro, Nicola

    2017-01-18

    In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness. In this editorial, we provide a brief overview of the current knowledge concerning the association between NAFLD and cardiac dysfunction.

  3. From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease

    PubMed Central

    Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia del Giudice, Emanuele; Santoro, Nicola

    2017-01-01

    In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness. In this editorial, we provide a brief overview of the current knowledge concerning the association between NAFLD and cardiac dysfunction. PMID:28144387

  4. Liver Test Results Do Not Identify Liver Disease in Adults with α-1 Antitrypsin Deficiency

    PubMed Central

    Clark, Virginia C.; Dhanasekaran, Renumathy; Brantly, Mark; Rouhani, Farshid; Schreck, Pamela; Nelson, David R.

    2012-01-01

    BACKGROUND & AIMS Liver disease is a significant cause of mortality among adults with α-1 antitrypsin (AAT) deficiency. Age and male sex are reported risk factors for liver disease. In the absence of adequate risk stratification, current recommendations are to intermittently test AAT-deficient adults for liver function. We evaluated this recommendation in a large group of adults with AAT deficiency, to determine the prevalence of increased levels of alanine aminotransferase (ALT) and identify risk factors for liver disease. METHODS We used the Alpha-1 Foundation DNA and Tissue Bank to identify a cross-section of AAT-deficient adults (n=647) with and without liver disease; individuals without AAT-deficiency were used as controls (n=152). Results from ALT tests were compared between groups. RESULTS The prevalence of liver disease among individuals with ATT-deficiency was 7.9%; an increased level of ALT was observed in 7.8% of ATT-deficient individuals, which did not differ significantly from controls. Mean levels of ALT fell within normal range for all groups. An increased level of ALT identified patients with liver disease with 11.9% sensitivity. The level of only γ- glutamyl transpeptidase was significantly higher in the AAT-deficient group than in controls (43 vs 30 IU/ml; P<.003). A childhood history of liver disease and male sex were risk factors for adult liver disease in the multivariate analysis. CONCLUSIONS An increased level of ALT does not identify adults with AAT deficiency who have liver disease. Male sex and liver disease during childhood might help identify those at risk. PMID:22835581

  5. Liver test results do not identify liver disease in adults with α(1)-antitrypsin deficiency.

    PubMed

    Clark, Virginia C; Dhanasekaran, Renumathy; Brantly, Mark; Rouhani, Farshid; Schreck, Pamela; Nelson, David R

    2012-11-01

    Liver disease is a significant cause of death among adults with α(1)-antitrypsin (A-AT) deficiency. Age and male sex are reported risk factors for liver disease. In the absence of adequate risk stratification, current recommendations are to intermittently test A-AT-deficient adults for liver function. We evaluated this recommendation in a large group of adults with A-AT deficiency to determine the prevalence of increased levels of alanine aminotransferase (ALT) and identify risk factors for liver disease. We used the Alpha-1 Foundation DNA and Tissue Bank to identify a cross section of A-AT-deficient adults (n = 647) with and without liver disease; individuals without A-AT deficiency were used as controls (n = 152). Results from ALT tests were compared between groups. The prevalence of liver disease among individuals with A-AT deficiency was 7.9%; an increased level of ALT was observed in 7.8% of A-AT-deficient individuals, which did not differ significantly from controls. Mean levels of ALT fell within normal range for all groups. An increased level of ALT identified patients with liver disease with 11.9% sensitivity. The level of only γ-glutamyl transpeptidase was significantly higher in the A-AT-deficient group than in controls (43 vs 30 IU/mL; P < .003). A childhood history of liver disease and male sex were risk factors for adult liver disease in the multivariate analysis. An increased level of ALT does not identify adults with A-AT deficiency who have liver disease. Male sex and liver disease during childhood might help identify those at risk. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood.

    PubMed

    Lluis, Anna; Depner, Martin; Gaugler, Beatrice; Saas, Philippe; Casaca, Vera Isabel; Raedler, Diana; Michel, Sven; Tost, Jorg; Liu, Jing; Genuneit, Jon; Pfefferle, Petra; Roponen, Marjut; Weber, Juliane; Braun-Fahrländer, Charlotte; Riedler, Josef; Lauener, Roger; Vuitton, Dominique Angèle; Dalphin, Jean-Charles; Pekkanen, Juha; von Mutius, Erika; Schaub, Bianca

    2014-02-01

    European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4(+)CD25(+) forkhead box protein 3 (FOXP3)(+) (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4(+)CD25(+), FOXP3(+) T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases. Copyright

  7. Possible role of insulin status in the increased lipogenic enzyme activity by dietary medium-chain triglyceride in rat liver.

    PubMed

    Takase, S; Hosoya, N

    1987-06-01

    The possible role of insulin status in the increase in liver lipogenic enzyme activities upon feeding medium-chain triglyceride (MCT) was investigated with streptozotocin-induced diabetic rats and insulin-treated diabetic rats. Rats were fed synthetic diets that contained either 2% corn oil (control), fat free, 13% MCT +2% corn oil, or 13% lard +2% corn oil, respectively. Feeding the MCT diet for 3 days increased serum ketone bodies in both the normal and diabetic rats. Insulin levels of MCT-fed rats tended to be higher than in normal animals. MCT feeding caused an enhancement of fatty acid synthetase (FAS) and malic enzyme (ME) in the liver of normal rats, whereas diabetic rats failed to register an increase in those activities due to MCT feeding. Administration of insulin to diabetic rats resulted in a recovery of the level of those enzyme activities to about the same degree as in each of the normal rat groups. It was interesting that diabetic MCT-fed rats with insulin treatment maintained higher enzyme activities in comparison to the lard and control groups. These results suggest that the increase in lipogenic enzyme activities caused by dietary MCT is presumably dependent on differences in insulin status.

  8. CHILDHOOD OBESITY

    PubMed Central

    Lakshman, Rajalakshmi; Elks, Cathy E.; Ong, Ken K.

    2013-01-01

    Clinical summary Childhood obesity has important consequences for health and wellbeing both during childhood and also in later adult life. The rising prevalence of childhood obesity poses a major public health challenge in both developed and developing countries by increasing the burden of chronic non-communicable diseases. Despite the urgent need for effective preventative strategies, there remains disagreement over its definition due to a lack of evidence on the optimal cut-offs linking childhood BMI to disease risks, and limited evidence on the most effective components of interventions to prevent childhood obesity. This article reviews the trends in childhood obesity, its genetic, nutritional and other risk factors, and preventative and treatment strategies. Particular emphasis is given to early-onset obesity in pre-school children, which, as a precursor to later childhood and adult obesity, provides insights into the developmental and genetic origins of obesity and also offers the potential for early preventative approaches with long-lasting benefits. PMID:23027812

  9. In-Group Ostracism Increases High-Fidelity Imitation in Early Childhood.

    PubMed

    Watson-Jones, Rachel E; Whitehouse, Harvey; Legare, Cristine H

    2016-01-01

    The Cyberball paradigm was used to examine the hypothesis that children use high-fidelity imitation as a reinclusion behavior in response to being ostracized by in-group members. Children (N = 176; 5- to 6-year-olds) were either included or excluded by in- or out-group members and then shown a video of an in-group or an out-group member enacting a social convention. Participants who were excluded by their in-group engaged in higher-fidelity imitation than those who were included by their in-group. Children who were included by an out-group and those who were excluded by an out-group showed no difference in imitative fidelity. Children ostracized by in-group members also displayed increased anxiety relative to children ostracized by out-group members. The data are consistent with the proposal that high-fidelity imitation functions as reinclusion behavior in the context of in-group ostracism.

  10. Increasing 3D Matrix Rigidity Strengthens Proliferation and Spheroid Development of Human Liver Cells in a Constant Growth Factor Environment.

    PubMed

    Bomo, Jérémy; Ezan, Frédéric; Tiaho, François; Bellamri, Medjda; Langouët, Sophie; Theret, Nathalie; Baffet, Georges

    2016-03-01

    Mechanical forces influence the growth and shape of virtually all tissues and organs. Recent studies show that increased cell contractibility, growth and differentiation might be normalized by modulating cell tensions. Particularly, the role of these tensions applied by the extracellular matrix during liver fibrosis could influence the hepatocarcinogenesis process. The objective of this study is to determine if 3D stiffness could influence growth and phenotype of normal and transformed hepatocytes and to integrate extracellular matrix (ECM) stiffness to tensional homeostasis. We have developed an appropriate 3D culture model: hepatic cells within three-dimensional collagen matrices with varying rigidity. Our results demonstrate that the rigidity influenced the cell phenotype and induced spheroid clusters development whereas in soft matrices, Huh7 transformed cells were less proliferative, well-spread and flattened. We confirmed that ERK1 played a predominant role over ERK2 in cisplatin-induced death, whereas ERK2 mainly controlled proliferation. As compared to 2D culture, 3D cultures are associated with epithelial markers expression. Interestingly, proliferation of normal hepatocytes was also induced in rigid gels. Furthermore, biotransformation activities are increased in 3D gels, where CYP1A2 enzyme can be highly induced/activated in primary culture of human hepatocytes embedded in the matrix. In conclusion, we demonstrated that increasing 3D rigidity could promote proliferation and spheroid developments of liver cells demonstrating that 3D collagen gels are an attractive tool for studying rigidity-dependent homeostasis of the liver cells embedded in the matrix and should be privileged for both chronic toxicological and pharmacological drug screening. © 2015 Wiley Periodicals, Inc.

  11. Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation.

    PubMed

    Otterdal, Kari; Haukeland, John Willy; Yndestad, Arne; Dahl, Tuva B; Holm, Sverre; Segers, Filip M; Gladhaug, Ivar P; Konopski, Zbigniew; Damås, Jan Kristian; Halvorsen, Bente; Aukrust, Pål

    2015-07-02

    The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism. We hypothesized that LIGHT could also have a pathogenic role in nonalcoholic fatty liver disease (NAFLD). Serum levels of LIGHT in NAFLD patients and control subjects, as well as LIGHT and interleukin (IL)-8 released from Huh7 (human hepatoma cell line) hepatocytes, were determined by enzyme-linked immunosorbent assay. The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR. (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin β receptor (LTβR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H2O2 (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes. We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction. Our findings should encourage further studies on the role of LIGHT in NAFLD development and progression.

  12. Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice

    PubMed Central

    Park, Han-Sol; Jang, Jung Eun; Ko, Myoung Seok; Woo, Sung Hoon; Kim, Bum Joong; Kim, Hyun Sik; Park, Hye Sun; Park, In-Sun; Koh, Eun Hee

    2016-01-01

    Background Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown. Methods Seven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD) with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day), for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver. Results Statin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα) were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels. Conclusion Statins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH. PMID:27098507

  13. Parental stress increases the effect of traffic-related air pollution on childhood asthma incidence.

    PubMed

    Shankardass, Ketan; McConnell, Rob; Jerrett, Michael; Milam, Joel; Richardson, Jean; Berhane, Kiros

    2009-07-28

    Exposure to traffic-related pollution (TRP) and tobacco smoke have been associated with new onset asthma in children. Psychosocial stress-related susceptibility has been proposed to explain social disparities in asthma. We investigated whether low socioeconomic status (SES) or high parental stress modified the effect of TRP and in utero tobacco smoke exposure on new onset asthma. We identified 2,497 children aged 5-9 years with no history of asthma or wheeze at study entry (2002-2003) into the Children's Health Study, a prospective cohort study in southern California. The primary outcome was parental report of doctor-diagnosed new onset asthma during 3 years of follow-up. Residential exposure to TRP was assessed using a line source dispersion model. Information about maternal smoking during pregnancy, parental education (a proxy for SES), and parental stress were collected in the study baseline questionnaire. The risk of asthma attributable to TRP was significantly higher for subjects with high parental stress (HR 1.51 across the interquartile range for TRP; 95% CI 1.16-1.96) than for subjects with low parental stress (HR 1.05, 95% CI 0.74-1.49; interaction P value 0.05). Stress also was associated with larger effects of in utero tobacco smoke. A similar pattern of increased risk of asthma was observed among children from low SES families who also were exposed to either TRP or in utero tobacco smoke. These results suggest that children from stressful households are more susceptible to the effects of TRP and in utero tobacco smoke on the development of asthma.

  14. Dendritic Cells Promote Macrophage Infiltration and Comprise a Substantial Proportion of Obesity-Associated Increases in CD11c+ Cells in Adipose Tissue and Liver

    PubMed Central

    Stefanovic-Racic, Maja; Yang, Xiao; Turner, Michael S.; Mantell, Benjamin S.; Stolz, Donna B.; Sumpter, Tina L.; Sipula, Ian J.; Dedousis, Nikolaos; Scott, Donald K.; Morel, Penelope A.; Thomson, Angus W.; O’Doherty, Robert M.

    2012-01-01

    Obesity-associated increases in adipose tissue (AT) CD11c+ cells suggest that dendritic cells (DC), which are involved in the tissue recruitment and activation of macrophages, may play a role in determining AT and liver immunophenotype in obesity. This study addressed this hypothesis. With the use of flow cytometry, electron microscopy, and loss-and-gain of function approaches, the contribution of DC to the pattern of immune cell alterations and recruitment in obesity was assessed. In AT and liver there was a substantial, high-fat diet (HFD)–induced increase in DC. In AT, these increases were associated with crown-like structures, whereas in liver the increase in DC constituted an early and reversible response to diet. Notably, mice lacking DC had reduced AT and liver macrophages, whereas DC replacement in DC-null mice increased liver and AT macrophage populations. Furthermore, delivery of bone marrow–derived DC to lean wild-type mice increased AT and liver macrophage infiltration. Finally, mice lacking DC were resistant to the weight gain and metabolic abnormalities of an HFD. Together, these data demonstrate that DC are elevated in obesity, promote macrophage infiltration of AT and liver, contribute to the determination of tissue immunophenotype, and play a role in systemic metabolic responses to an HFD. PMID:22851575

  15. Decreasing Computer Anxiety and Increasing Computer Usage among Early Childhood Education Majors through a Hands-On Approach in a Nonthreatening Environment.

    ERIC Educational Resources Information Center

    Castleman, Jacquelyn B.

    This practicum was designed to lessen the computer anxiety of early childhood education majors enrolled in General Curriculum or General Methods courses, to assist them in learning more about computer applications, and to increase the amount of time spent using computers. Weekly guidelines were given to the students, and a hands-on approach was…

  16. Administration of granulocyte colony stimulating factor after liver transplantation leads to an increased incidence and severity of ischemic biliary lesions in the rat model

    PubMed Central

    Dirsch, Olaf; Chi, Haidong; Ji, Yuan; Gu, Yan Li; Broelsch, Christoph E; Dahmen, Uta

    2006-01-01

    AIM: Recently it has been reported that granulocyte colony stimulating factor (G-CSF) can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a recipient of an organ graft with already impaired perfusion might cause further deterioration in the transplanted organ. This study evaluated whether G-CSF treatment worsens liver perfusion following liver transplantation in the rat model. METHODS: A non-arterialized rat liver transplantation model was employed to evaluate the effect of G-CSF treatment on the liver in a syngeneic and allogeneic strain combination. Study outcomes included survival time and liver damage as investigated by liver enzymes and liver histology. Observation times were 1 d, 1 wk and 12 wk. RESULTS: Rats treated with G-CSF had increased incidence and severity of biliary damage following liver transplantation. In these animals, hepatocellular necrosis was accentuated in the centrilobular region. These lesions are indicative of impaired perfusion in G-CSF treated animals. CONCLUSION: G-CSF should be used with caution in recipients of liver transplantation, as treatment might enhance preexisting, undetected perfusion problems and ultimately lead to ischemia induced biliary complications. PMID:16937499

  17. Increased alpha-amylase response to an acute psychosocial stress challenge in healthy adults with childhood adversity.

    PubMed

    Kuras, Yuliya I; McInnis, Christine M; Thoma, Myriam V; Chen, Xuejie; Hanlin, Luke; Gianferante, Danielle; Rohleder, Nicolas

    2017-01-01

    Childhood adversity is highly prevalent and linked to lasting psychological and physiological consequences. A potential mechanism for negative health outcomes is altered stress reactivity. While previous research has addressed associations of childhood adversity with stress system reactivity, sympathetic nervous system (SNS) stress reactivity is understudied. We therefore set out here to examining salivary alpha-amylase (sAA) reactivity in relation with childhood adversity. Forty-one healthy adult subjects (n = 24 male; n = 17 female) aged 18-34 years underwent the Trier Social Stress Test (TSST) and completed the Childhood Trauma Questionnaire (CTQ). Saliva for measurement of sAA was collected at three time points; before the TSST, immediately after, and 10 min post-TSST. We found that those with childhood trauma had a higher overall sAA response to the TSST, as seen in a repeated measures ANOVA (CTQ by time interaction: F(1.8,71.5) = 6.46, p = .01) and an independent samples t-test indicating higher sAA baseline to peak response (t = 3.22, p = .003). There was also a positive correlation between sAA reactivity and the CTQ subscales of childhood physical abuse (r = .46, p = .005) and emotional abuse (r = .37, p = .024). Healthy adults with low-to-moderate childhood adversity had a heightened sAA response immediately following the stressor. Higher SNS reactivity could be a link to negative health outcomes in adults with early adversity. Future research should address whether altered sAA reactivity is predictive of negative health outcomes in those with childhood adversity.

  18. Increased long-latency reflex activity as a sufficient explanation for childhood hypertonic dystonia: a neuromorphic emulation study

    NASA Astrophysics Data System (ADS)

    Sohn, Won J.; Niu, Chuanxin M.; Sanger, Terence D.

    2015-06-01

    Objective. Childhood dystonia is a movement disorder that interferes with daily movements and can have a devastating effect on quality of life for children and their families. Although injury to basal ganglia is associated with dystonia, the neurophysiological mechanisms leading to the clinical manifestations of dystonia are not understood. Previous work suggested that long-latency stretch reflex (LLSR) is hyperactive in children with hypertonia due to secondary dystonia. We hypothesize that abnormal activity in motor cortices may cause an increase in the LLSR leading to hypertonia. Approach. We modeled two possibilities of hyperactive LLSR by either creating a tonic involuntary drive to cortex, or increasing the synaptic gain in cortical neurons. Both models are emulated using programmable very-large-scale-integrated-circuit hardware to test their sufficiency for producing dystonic symptoms. The emulation includes a joint with two Hill-type muscles, realistic muscle spindles, and 2,304 Izhikevich-type spiking neurons. The muscles are regulated by a monosynaptic spinal pathway with 32 ms delay and a long-latency pathway with 64 ms loop-delay representing transcortical/supra-spinal connections. Main results. When the limb is passively stretched, both models produce involuntary resistance with increased antagonist EMG responses similar to human data; also the muscle relaxation is delayed similar to human data. Both models predict reduced range of motion in voluntary movements. Significance. Although our model is a highly simplified and limited representation of reflex pathways, it shows that increased activity of the LLSR is by itself sufficient to cause many of the features of hypertonic dystonia.

  19. Using quality improvement methods to increase use of pain prevention strategies for childhood vaccination.

    PubMed

    Schurman, Jennifer Verrill; Deacy, Amanda D; Johnson, Rebecca J; Parker, Jolynn; Williams, Kristi; Wallace, Dustin; Connelly, Mark; Anson, Lynn; Mroczka, Kevin

    2017-02-08

    To increase evidence-based pain prevention strategy use during routine vaccinations in a pediatric primary care clinic using quality improvement methodology. Specific intervention strategies (i.e., comfort positioning, nonnutritive sucking and sucrose analgesia, distraction) were identified, selected and introduced in three waves, using a Plan-Do-Study-Act framework. System-wide change was measured from baseline to post-intervention by: (1) percent of vaccination visits during which an evidence-based pain prevention strategy was reported as being used; and (2) caregiver satisfaction ratings following the visit. Additionally, self-reported staff and caregiver attitudes and beliefs about pain prevention were measured at baseline and 1-year post-intervention to assess for possible long-term cultural shifts. Significant improvements were noted post-intervention. Use of at least one pain prevention strategy was documented at 99% of patient visits and 94% of caregivers were satisfied or very satisfied with the pain prevention care received. Parents/caregivers reported greater satisfaction with the specific pain prevention strategy used [t(143) = 2.50, P ≤ 0.05], as well as greater agreement that the pain prevention strategies used helped their children's pain [t(180) = 2.17, P ≤ 0.05] and that they would be willing to use the same strategy again in the future [t(179) = 3.26, P ≤ 0.001] as compared to baseline. Staff and caregivers also demonstrated a shift in attitudes from baseline to 1-year post-intervention. Specifically, staff reported greater agreement that the pain felt from vaccinations can result in harmful effects [2.47 vs 3.10; t(70) = -2.11, P ≤ 0.05], less agreement that pain from vaccinations is "just part of the process" [3.94 vs 3.23; t(70) = 2.61, P ≤ 0.05], and less agreement that parents expect their children to experience pain during vaccinations [4.81 vs 4.38; t(69) = 2.24, P ≤ 0.05]. Parents/caregivers reported more favorable attitudes

  20. Using quality improvement methods to increase use of pain prevention strategies for childhood vaccination

    PubMed Central

    Schurman, Jennifer Verrill; Deacy, Amanda D; Johnson, Rebecca J; Parker, Jolynn; Williams, Kristi; Wallace, Dustin; Connelly, Mark; Anson, Lynn; Mroczka, Kevin

    2017-01-01

    AIM To increase evidence-based pain prevention strategy use during routine vaccinations in a pediatric primary care clinic using quality improvement methodology. METHODS Specific intervention strategies (i.e., comfort positioning, nonnutritive sucking and sucrose analgesia, distraction) were identified, selected and introduced in three waves, using a Plan-Do-Study-Act framework. System-wide change was measured from baseline to post-intervention by: (1) percent of vaccination visits during which an evidence-based pain prevention strategy was reported as being used; and (2) caregiver satisfaction ratings following the visit. Additionally, self-reported staff and caregiver attitudes and beliefs about pain prevention were measured at baseline and 1-year post-intervention to assess for possible long-term cultural shifts. RESULTS Significant improvements were noted post-intervention. Use of at least one pain prevention strategy was documented at 99% of patient visits and 94% of caregivers were satisfied or very satisfied with the pain prevention care received. Parents/caregivers reported greater satisfaction with the specific pain prevention strategy used [t(143) = 2.50, P ≤ 0.05], as well as greater agreement that the pain prevention strategies used helped their children’s pain [t(180) = 2.17, P ≤ 0.05] and that they would be willing to use the same strategy again in the future [t(179) = 3.26, P ≤ 0.001] as compared to baseline. Staff and caregivers also demonstrated a shift in attitudes from baseline to 1-year post-intervention. Specifically, staff reported greater agreement that the pain felt from vaccinations can result in harmful effects [2.47 vs 3.10; t(70) = -2.11, P ≤ 0.05], less agreement that pain from vaccinations is “just part of the process” [3.94 vs 3.23; t(70) = 2.61, P ≤ 0.05], and less agreement that parents expect their children to experience pain during vaccinations [4.81 vs 4.38; t(69) = 2.24, P ≤ 0.05]. Parents/caregivers reported

  1. Precision-cut liver slices from diet-induced obese rats exposed to ethanol are susceptible to oxidative stress and increased fatty acid synthesis.

    PubMed

    Duryee, Michael J; Willis, Monte S; Schaffert, Courtney S; Reidelberger, Roger D; Dusad, Anand; Anderson, Daniel R; Klassen, Lynell W; Thiele, Geoffrey M

    2014-02-01

    Oxidative stress from fat accumulation in the liver has many deleterious effects. Many believe that there is a second hit that causes relatively benign fat accumulation to transform into liver failure. Therefore, we evaluated the effects of ethanol on ex vivo precision-cut liver slice cultures (PCLS) from rats fed a high-fat diet resulting in fatty liver. Age-matched male Sprague-Dawley rats were fed either high-fat (obese) (45% calories from fat, 4.73 kcal/g) or control diet for 13 mo. PCLS were prepared, incubated with 25 mM ethanol for 24, 48, and 72 h, harvested, and evaluated for ethanol metabolism, triglyceride production, oxidative stress, and cytokine expression. Ethanol metabolism and acetaldehyde production decreased in PCLS from obese rats compared with age-matched controls (AMC). Increased triglyceride and smooth muscle actin production was observed in PCLS from obese rats compared with AMC, which further increased following ethanol incubation. Lipid peroxidation, measured by thiobarbituric acid reactive substances assay, increased in response to ethanol, whereas GSH and heme oxygenase I levels were decreased. TNF-α and IL-6 levels were increased in the PCLS from obese rats and increased further with ethanol incubation. Diet-induced fatty liver increases the susceptibility of the liver to toxins such as ethanol, possibly by the increased oxidative stress and cytokine production. These findings support the concept that the development of fatty liver sensitizes the liver to the effects of ethanol and leads to the start of liver failure, necrosis, and eventually cirrhosis.

  2. Developmentally dynamic genome: Evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence

    PubMed Central

    Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi

    2015-01-01

    The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems’ developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact. PMID:25944445

  3. Developmentally dynamic genome: Evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence.

    PubMed

    Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi

    2015-05-06

    The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems' developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact.

  4. Hepatocyte X-box binding protein 1 deficiency increases liver injury in mice fed a high-fat/sugar diet

    PubMed Central

    Henkel, Anne S.; LeCuyer, Brian E.; Schipma, Matthew J.; Anderson, Kristy A.; Green, Richard M.

    2015-01-01

    Fatty liver is associated with endoplasmic reticulum stress and activation of the hepatic unfolded protein response (UPR). Reduced hepatic expression of the UPR regulator X-box binding protein 1 spliced (XBP1s) is associated with human nonalcoholic steatohepatitis (NASH), and feeding mice a high-fat diet with fructose/sucrose causes progressive, fibrosing steatohepatitis. This study examines the role of XBP1 in nonalcoholic fatty liver injury and fatty acid-induced cell injury. Hepatocyte-specific Xbp1-deficient (Xbp1−/−) mice were fed a high-fat/sugar (HFS) diet for up to 16 wk. HFS-fed Xbp1−/− mice exhibited higher serum alanine aminotransferase levels compared with Xbp1fl/fl controls. RNA sequencing and Gene Ontogeny pathway analysis of hepatic mRNA revealed that apoptotic process, inflammatory response, and extracellular matrix structural constituent pathways had enhanced activation in HFS-fed Xbp1−/− mice. Liver histology demonstrated enhanced injury and fibrosis but less steatosis in the HFS-fed Xbp1−/− mice. Hepatic Col1a1 and Tgfβ1 gene expression, as well as Chop and phosphorylated JNK (p-JNK), were increased in Xbp1−/− compared with Xbp1fl/fl mice after HFS feeding. In vitro, stable XBP1-knockdown Huh7 cells (Huh7-KD) and scramble control cells (Huh7-SCR) were generated and treated with palmitic acid (PA) for 24 h. PA-treated Huh7-KD cells had increased cytotoxicity measured by lactate dehydrogenase release, apoptotic nuclei, and caspase3/7 activity assays compared with Huh7-SCR cells. CHOP and p-JNK expression was also increased in Huh7-KD cells following PA treatment. In conclusion, loss of XBP1 enhances injury in both in vivo and in vitro models of fatty liver injury. We speculate that hepatic XBP1 plays an important protective role in pathogenesis of NASH. PMID:26472223

  5. Increased risk of nonalcoholic fatty liver disease with occupational stress in Chinese policemen

    PubMed Central

    Li, Chen; Xing, Jing-Jing; Shan, An-Qi; Leng, Ling; Liu, Jin-Chuan; Yue, Song; Yu, Hao; Chen, Xi; Tian, Feng-Shi; Tang, Nai-Jun

    2016-01-01

    Abstract Nonalcoholic fatty liver disease (NAFLD) and occupational stress have been recognized as major public health concerns. We aimed to explore whether occupational stress was associated with NAFLD in a police population. A total of 6559 male police officers were recruited for this prospective study in April 2007. Among them, 2367 eligible subjects participated in follow-up from 2008 to 2011. NAFLD was diagnosed based on standard criteria. Occupational stress was evaluated by Occupational Stress Inventory-Revised scores. The incidence of NAFLD was 31.2% in the entire police. After adjusting for traditional risk factors, moderate occupational stress (MOS), high occupational stress (HOS), and high personal strain (HPS) were risk factors (MOS: hazard ratio [HR] = 1.237, 95% confidence interval [CI] = 1.049–1.460; HOS: HR = 1.727, 95% CI = 1.405–2.124; HPS: HR = 3.602, 95% CI = 1.912–6.787); and low occupational stress (LOS) and low personal strain (LPS) were protective factors (LOS: HR = 0.366, 95% CI = 0.173–0.776; LPS: HR = 0.490, 95% CI = 0.262–0.919) for NAFLD in the entire police cohort. HOS and HPS remained robust among traffic police. HOS and HPS were independent predictors for the development of NAFLD in a Chinese police population. Additional future prospective investigations are warranted to validate our findings. PMID:27861366

  6. Increasing Fears in Childhood.

    ERIC Educational Resources Information Center

    Taddeo, Danielle

    This study involved a survey based on a preliminary poll asking children in a Bronx (New York) classroom (N=26) to list their fears. Many children have fears at all levels of severity. The general perception seems to be that in recent years children are more stressed and less equipped to handle fear. The initial poll revealed that children's fears…

  7. Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective- and cross-sectional cohort studies.

    PubMed

    Varese, Filippo; Smeets, Feikje; Drukker, Marjan; Lieverse, Ritsaert; Lataster, Tineke; Viechtbauer, Wolfgang; Read, John; van Os, Jim; Bentall, Richard P

    2012-06-01

    Evidence suggests that adverse experiences in childhood are associated with psychosis. To examine the association between childhood adversity and trauma (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death, and bullying) and psychosis outcome, MEDLINE, EMBASE, PsychINFO, and Web of Science were searched from January 1980 through November 2011. We included prospective cohort studies, large-scale cross-sectional studies investigating the association between childhood adversity and psychotic symptoms or illness, case-control studies comparing the prevalence of adverse events between psychotic patients and controls using dichotomous or continuous measures, and case-control studies comparing the prevalence of psychotic symptoms between exposed and nonexposed subjects using dichotomous or continuous measures of adversity and psychosis. The analysis included 18 case-control studies (n = 2048 psychotic patients and 1856 nonpsychiatric controls), 10 prospective and quasi-prospective studies (n = 41,803) and 8 population-based cross-sectional studies (n = 35,546). There were significant associations between adversity and psychosis across all research designs, with an overall effect of OR = 2.78 (95% CI = 2.34-3.31). The integration of the case-control studies indicated that patients with psychosis were 2.72 times more likely to have been exposed to childhood adversity than controls (95% CI = 1.90-3.88). The association between childhood adversity and psychosis was also significant in population-based cross-sectional studies (OR = 2.99 [95% CI = 2.12-4.20]) as well as in prospective and quasi-prospective studies (OR = 2.75 [95% CI = 2.17-3.47]). The estimated population attributable risk was 33% (16%-47%). These findings indicate that childhood adversity is strongly associated with increased risk for psychosis.

  8. Childhood Adversities Increase the Risk of Psychosis: A Meta-analysis of Patient-Control, Prospective- and Cross-sectional Cohort Studies

    PubMed Central

    Varese, Filippo; Smeets, Feikje; Drukker, Marjan; Lieverse, Ritsaert; Lataster, Tineke; Viechtbauer, Wolfgang; Read, John; van Os, Jim; Bentall, Richard P.

    2012-01-01

    Evidence suggests that adverse experiences in childhood are associated with psychosis. To examine the association between childhood adversity and trauma (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death, and bullying) and psychosis outcome, MEDLINE, EMBASE, PsychINFO, and Web of Science were searched from January 1980 through November 2011. We included prospective cohort studies, large-scale cross-sectional studies investigating the association between childhood adversity and psychotic symptoms or illness, case-control studies comparing the prevalence of adverse events between psychotic patients and controls using dichotomous or continuous measures, and case-control studies comparing the prevalence of psychotic symptoms between exposed and nonexposed subjects using dichotomous or continuous measures of adversity and psychosis. The analysis included 18 case-control studies (n = 2048 psychotic patients and 1856 nonpsychiatric controls), 10 prospective and quasi-prospective studies (n = 41 803) and 8 population-based cross-sectional studies (n = 35 546). There were significant associations between adversity and psychosis across all research designs, with an overall effect of OR = 2.78 (95% CI = 2.34–3.31). The integration of the case-control studies indicated that patients with psychosis were 2.72 times more likely to have been exposed to childhood adversity than controls (95% CI = 1.90–3.88). The association between childhood adversity and psychosis was also significant in population-based cross-sectional studies (OR = 2.99 [95% CI = 2.12–4.20]) as well as in prospective and quasi-prospective studies (OR = 2.75 [95% CI = 2.17–3.47]). The estimated population attributable risk was 33% (16%–47%). These findings indicate that childhood adversity is strongly associated with increased risk for psychosis. PMID:22461484

  9. Does physical abuse, sexual abuse, or neglect in childhood increase the likelihood of same-sex sexual relationships and cohabitation? A prospective 30-year follow-up.

    PubMed

    Wilson, Helen W; Widom, Cathy Spatz

    2010-02-01

    Existing cross-sectional research suggests associations between physical and sexual abuse in childhood and same-sex sexual orientation in adulthood. This study prospectively examined whether abuse and/or neglect in childhood were associated with increased likelihood of same-sex partnerships in adulthood. The sample included physically abused (N = 85), sexually abused (N = 72), and neglected (N = 429) children (ages 0-11) with documented cases during 1967-1971 who were matched with non-maltreated children (N = 415) and followed into adulthood. At approximately age 40, participants (483 women and 461 men) were asked about romantic cohabitation and sexual partners, in the context of in-person interviews covering a range of topics. Group (abuse/neglect versus control) differences were assessed with cross-tabulations and logistic regression. A total of 8% of the overall sample reported any same-sex relationship (cohabitation or sexual partners). Childhood physical abuse and neglect were not significantly associated with same-sex cohabitation or sexual partners. Individuals with documented histories of childhood sexual abuse were significantly more likely than controls to report ever having had same-sex sexual partners (OR = 2.81, 95% CI = 1.16-6.80, p < or = .05); however, only men with histories of childhood sexual abuse were significantly more likely than controls to report same-sex sexual partners (OR = 6.75, 95% CI = 1.53-29.86, p < or = .01). These prospective findings provide tentative evidence of a link between childhood sexual abuse and same-sex sexual partnerships among men, although further research is needed to explore this relationship and to examine potential underlying mechanisms.

  10. Intergenerational violence in Burundi: Experienced childhood maltreatment increases the risk of abusive child rearing and intimate partner violence

    PubMed Central

    Crombach, Anselm; Bambonyé, Manassé

    2015-01-01

    Background Experiencing abuse during childhood affects the psychological well-being of individuals throughout their lives and may even influence their offspring by enhancing the likelihood of an intergenerational transmission of violence. Understanding the effects of childhood maltreatment on child-rearing practices and intimate partner violence might be of particular importance to overcome the consequences of violent conflicts in African societies. Objective Using Burundi as an example, we aimed to explore the associations between childhood maltreatment, intimate partner violence, perceived partner intimidation, gender and the probability of violently acting out against one's own children or romantic partner. Methods Amongst a sample of 141 men and 141 women in the capital of Burundi, we identified those who had biological children and those who lived or had lived in relationships. Using culturally appropriate instruments, we enquired about their exposure to childhood maltreatment and partner violence as well as their inclinations to act out violently. Results We found that childhood maltreatment and perceived partner intimidation were strong predictors for the perpetration of violence against children. Moreover, we found that women were more likely to use violence against children if they experienced partner violence and less likely to resort to violence if they felt intimidated. Men were more likely to perpetrate violence against their partner. Childhood maltreatment was again a strong predictor. The more women experienced partner violence, the more they fought back. Conclusions Childhood maltreatment is a strong predictor for domestic violence and has to be addressed to interrupt the cycle of violence in post-conflict countries. PMID:26679146

  11. Increased accumulation of 4-hydroxynonenal adducts in female GSTA4/PPAR alpha double knockout mice enhance steatosis and inflammation in a model of pediatric nonalcoholic fatty liver disease

    USDA-ARS?s Scientific Manuscript database

    Hepatocellular injury resulting from increased lipid peroxidation products and oxidative stress is considered a potential mechanism driving the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitsis (NASH). To test the significance of lipid peroxidation and protein...

  12. Chicken thigh, chicken liver, and iron-fortified wheat flour increase iron uptake in an in vitro digestion/Caco-2 cell model.

    PubMed

    Pachón, Helena; Stoltzfus, Rebecca J; Glahn, Raymond P

    2008-12-01

    The objective of this study was to test meat and fortified-food combinations to identify those that optimize iron uptake in an in vitro digestion/Caco-2 cell model, a proxy for iron bioavailability. Four experiments tested combinations of meats such as chicken (blood, spleen, liver, thigh), beef (cube steak), and fish (whole-fish meal) with iron-fortified foods (rice cereal, maize-soy flour, wheat flour). Chicken liver, thigh, spleen, blood, or fish meal increased the Caco-2 cell iron uptake from these combined with rice cereal (P< .05). Chicken liver, thigh, blood, and beef increased the Caco-2 cell iron uptake from these combined with wheat flour (P< .05). Chicken liver and thigh were tested further. Compared with the liver or thigh alone, adding fortified foods to these meats did not increase the Caco-2 cell iron uptake (P >or= .05). Adding either meat to the 3 fortified foods increased the Caco-2 cell iron uptake of the fortified foods (P< .05). Chicken liver, chicken thigh, and wheat flour were selected for an infant porridge because the combinations with the highest Caco-2 cell iron uptake were chicken thigh + wheat flour, chicken liver + wheat flour, and chicken liver + maize-soy flour, and wheat flour was the least expensive fortified food sold in the target population. Per unit of iron, the chicken thigh + wheat flour and chicken liver + wheat flour combinations resulted in the highest bioavailable iron. In the proportion of 3:1 fortified food:meat examined, meat increases the bioavailability of iron-fortified foods, but iron-fortified foods do not enhance total iron bioavailability when added to meat.

  13. Adjuvant treatment with tumor-targeting Salmonella typhimurium A1-R reduces recurrence and increases survival after liver metastasis resection in an orthotopic nude mouse model.

    PubMed

    Murakami, Takashi; Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2015-12-08

    Colon cancer liver metastasis is often the lethal aspect of this disease. Well-isolated metastases are candidates for surgical resection, but recurrence is common. Better adjuvant treatment is therefore needed to reduce or prevent recurrence. In the present study, HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used to establish liver metastases in nude mice. Mice with a single liver metastasis were randomized into bright-light surgery (BLS) or the combination of BLS and adjuvant treatment with tumor-targeting S. typhimurium A1-R. Residual tumor fluorescence after BLS was clearly visualized at high magnification by fluorescence imaging. Adjuvant treatment with S. typhimurium A1-R was highly effective to increase survival and disease-free survival after BLS of liver metastasis. The results suggest the future clinical potential of adjuvant S. typhimurium A1-R treatment after liver metastasis resection.

  14. Living donor liver transplantation does not increase tumor recurrence of hepatocellular carcinoma compared to deceased donor transplantation

    PubMed Central

    Xiao, Guang-Qin; Song, Jiu-Lin; Shen, Shu; Yang, Jia-Yin; Yan, Lu-Nan

    2014-01-01

    AIM: To compare the recurrence-free survival (RFS) and overall survival (OS) of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT). METHODS: We retrospectively collected clinical data from 408 liver cancer patients from February 1999 to September 2012. We used the chi-squared test or Fisher’s exact test to analyze the characteristics of LDLT and DDLT. Kaplan-Meier analysis was used to compare the RFS and OS in HCC. RESULTS: Three hundred sixty HBV-positive patients (276 DDLT and 84 LDLT) were included in this study. The mean follow-up time was 27.1 mo (range 1.1-130.8 mo). One hundred eighty-five (51.2%) patients died during follow-up. The 1-, 3-, and 5-year RFS rates for LDLT were 85.2%, 55.7%, and 52.9%, respectively; for DDLT, the RFS rates were 73.2%, 49.1%, and 45.3% (P = 0.115). The OS rates were similar between the LDLT and DDLT recipients, with 1-, 3-, and 5-year survival rates of 81.8%, 49.5%, and 43.0% vs 69.5%, 43.0%, and 38.3%, respectively (P = 0.30). The outcomes of HCC according to the Milan criteria after LDLT and DDLT were not significantly different (for LDLT: 1-, 3-, and 5-year RFS: 94.7%, 78.7%, and 78.7% vs 89.2%, 77.5%, and 74.5%, P = 0.50; for DDLT: 86.1%, 68.8%, and 68.8% vs 80.5%, 62.2%, and 59.8% P = 0.53). CONCLUSION: The outcomes of LDLT for HCC are not worse compared to the outcomes of DDLT. LDLT does not increase tumor recurrence of HCC compared to DDLT. PMID:25152599

  15. Ciprofibrate increases cholesteryl ester transfer protein gene expression and the indirect reverse cholesterol transport to the liver

    PubMed Central

    2009-01-01

    Background CETP is a plasma protein that modulates atherosclerosis risk through its HDL-cholesterol reducing action. The aim of this work was to examine the effect of the PPARα agonist, ciprofibrate, on the CETP gene expression, in the presence and absence of apolipoprotein (apo) CIII induced hypertriglyceridemia, and its impact on the HDL metabolism. Results Mice expressing apo CIII and/or CETP and non-transgenic littermates (CIII, CIII/CETP, CETP, non-Tg) were treated with ciprofibrate during 3 weeks. Drug treatment reduced plasma triglycerides (30-43%) and non-esterified fatty acids (19-47%) levels. Cholesterol (chol) distribution in plasma lipoprotein responses to ciprofibrate treatment was dependent on the genotypes. Treated CIII expressing mice presented elevation in VLDL-chol and reduction in HDL-chol. Treated CETP expressing mice responded with reduction in LDL-chol whereas in non-Tg mice the LDL-chol increased. In addition, ciprofibrate increased plasma post heparin lipoprotein lipase activity (1.3-2.1 fold) in all groups but hepatic lipase activity decreased in treated CETP and non-Tg mice. Plasma CETP activity and liver CETP mRNA levels were significantly increased in treated CIII/CETP and CETP mice (30-100%). Kinetic studies with 3H-cholesteryl ether (CEt) labelled HDL showed a 50% reduction in the 3H-CEt found in the LDL fraction in ciprofibrate treated compared to non-treated CETP mice. This means that 3H-CEt transferred from HDL to LDL was more efficiently removed from the plasma in the fibrate treated mice. Accordingly, the amount of 3H-CEt recovered in the liver 6 hours after HDL injection was increased by 35%. Conclusion Together these data showed that the PPARα agonist ciprofibrate stimulates CETP gene expression and changes the cholesterol flow through the reverse cholesterol transport, increasing plasma cholesterol removal through LDL. PMID:19930639

  16. Glycine facilitates gamma-glutamylcysteinylethyl ester-mediated increase in liver glutathione level.

    PubMed

    Nishida, K; Ohta, Y; Ishiguro, I

    1997-08-27

    gamma-Glutamylcysteinylethyl ester (gamma-GCE) increases reduced glutathione (GSH) levels in GSH-depleted rat hepatocytes. Because glycine, a constituent of GSH, exists at 0.3 to 0.4 mM in rat plasma, we examined the influence of glycine added to the medium on the action of gamma-GCE to increase GSH levels in the rat hepatocytes. Glycine (0.2-0.8 mM) dose-dependently enhanced gamma-GCE-mediated increase in intracellular GSH levels with an increase in intracellular gamma-GCE levels. These results indicate that exogenous glycine facilitates gamma-GCE-mediated increase in intracellular GSH levels in rat hepatocytes possibly by enhancing the uptake of gamma-GCE into the cells.

  17. Acetaminophen availability increases in Canada with no increase in the incidence of reports of inpatient hospitalizations with acetaminophen overdose and acute liver toxicity.

    PubMed

    Prior, Mary Jane; Cooper, Kimberly; Cummins, Peter; Bowen, Debra

    2004-01-01

    In September 1999, several Canadian provinces had place-of-sale restrictions lifted that had limited the sale of acetaminophen >325 mg and packages >24 tablets (any strength) to pharmacies only. This allowed the sale of all strengths of immediate-release acetaminophen in all package sizes in nonpharmacy locations. This study's purpose was to explore the effect that lifting restrictions on acetaminophen place of sale may have had on reported hospitalizations in Canada related to acetaminophen overdose toxicity. Using hospital discharge data, provinces with no preexisting restrictions on place of sale were compared with those in which restrictions were lifted in September 1999. Cases of reported APAP overdose included ICD-9/9-CM code 965.4, ICD-9 code E850.2, or ICD-9-CM code E850.4. Cases with reported acute liver toxicity included ICD-9/9-CM codes 570, 572.2, 572.4, V42.7, or procedure code 50.5. There were no significant differences between the 1.5-year periods pre- and post-September 1999 in annual incidence rates per 100,000 persons ages >/=12 years of hospitalizations reported with acetaminophen overdose, either overall or limited to those with death as an outcome, or in hospitalization reports with both acetaminophen overdose and acute liver toxicity, either overall (provinces with no restrictions: pre = 0.70, post = 0.80, P = 0.6328; provinces with restrictions lifted in September 1999: pre = 0.49, post = 0.47, P = 0.8649) or limited to those with death as an outcome (provinces with no restrictions: pre = 0.22, post = 0.12, P = 0.3030; provinces with restrictions lifted in September 1999: pre = 0.13, post = 0.09, P = 0.3589). In conclusion, the decision to lift Canadian place-of-sale restrictions increased acetaminophen availability and did not increase the rate of reported hospitalizations related to acetaminophen overdose toxicity.

  18. Increased Childhood Mortality and Arsenic in Drinking Water in Matlab, Bangladesh: A Population-Based Cohort Study

    PubMed Central

    Rahman, Mahfuzar; Sohel, Nazmul; Yunus, Mohammad; Chowdhury, Mahbub Elahi; Hore, Samar Kumar; Zaman, Khalequ; Bhuiya, Abbas; Streatfield, Peter Kim

    2013-01-01

    Background Arsenic in drinking water was associated with increased risk of all-cause, cancer, and cardiovascular death in adults. However, the extent to which exposure is related to all-cause and deaths from cancer and cardiovascular condition in young age is unknown. Therefore, we prospectively assessed whether long-term and recent arsenic exposures are associated with all-cause and cancer and cardiovascular mortalities in Bangladeshi childhood population. Methods and Findings We assembled a cohort of 58406 children aged 5–18 years from the Health and Demographic Surveillance System of icddrb in Bangladesh and followed during 2003–2010. There were 185 non-accidental deaths registered in-about 0.4 million person-years of observation. We calculated hazard ratios for cause-specific death in relation to exposure at baseline (µg/L), time-weighted lifetime average (µg/L) and cumulative concentration (µg-years/L). After adjusting covariates, hazard ratios (HRs) for all-cause childhood deaths comparing lifetime average exposure 10–50.0, 50.1–150.0, 150.1–300.0 and ≥300.1µg/L were 1.37 (95% confidence interval [CI], 0.74–2.57), 1.44 (95% CI, 0.88–2.38), 1.22 (95% CI, 0.75–1.98) and 1.88 (95% CI, 1.14–3.10) respectively. Significant increased risk was also observed for baseline (P for trend = 0.023) and cumulative exposure categories (P for trend = 0.036). Girls had higher mortality risk compared to boys (HR for girls 1.79, 1.21, 1.64, 2.31; HR for boys 0.52, 0.53, 1.14, 0.99) in relation to baseline exposure. For all cancers and cardiovascular deaths combined, multivariable adjusted HRs amounted to 1.53 (95% CI 0.51–4.57); 1.29 (95% CI 0.43–3.87); 2.18 (95%CI 1.15–4.16) for 10.0–50.0, 50.1–150.0, and ≥150.1, comparing lowest exposure as reference (P for trend = 0.009). Adolescents had higher mortality risk compared to children (HRs = 1.53, 95% CI 1.03–2.28 vs. HRs = 1.30, 95% CI 0.78–2.17). Conclusions Arsenic

  19. Aging and a long-term diabetes mellitus increase expression of 1 α-hydroxylase and vitamin D receptors in the rat liver.

    PubMed

    Vuica, Ana; Ferhatović Hamzić, Lejla; Vukojević, Katarina; Jerić, Milka; Puljak, Livia; Grković, Ivica; Filipović, Natalija

    2015-12-01

    Diabetes mellitus (DM) is a metabolic disorder associated with serious liver complications. As a metabolic chronic disease, DM is very common in the elderly. Recent studies suggest ameliorating effects of vitamin D on metabolic and oxidative stress in the liver tissue in an experimental model of DM. The aim of this study was to investigate the expression of vitamin D receptors (VDRs) and 1α-hydroxylase, the key enzyme for the production of active vitamin D form (calcitriol) in the liver during long-term diabetes mellitus type 1 (DM1) in aging rats. We performed immunohistochemical analysis of liver expression of 1α-hydroxylase and VDRs during aging in long-term streptozotocin-induced DM1. 1α-Hydroxylase was identified in the monocyte/macrophage system of the liver. In addition to the nuclear expression, we also observed the expression of VDR in membranes of lipid droplets within hepatocytes. Aging and long-term DM1 resulted in significant increases in the number of 1α-hydroxylase immunoreactive cells, as well as the percentage of strongly positive VDR hepatocytes. In conclusion, the liver has the capacity for active vitamin D synthesis in its monocyte/macrophage system that is substantially increased in aging and long-term diabetes mellitus. These conditions are also characterized by significant increases in vitamin D receptor expression in hepatocytes. The present study suggests that VDR signaling system could be a potential target in prevention of liver complications caused by diabetes and aging.

  20. Oxidative stress of brain and liver is increased by Wi-Fi (2.45GHz) exposure of rats during pregnancy and the development of newborns.

    PubMed

    Çelik, Ömer; Kahya, Mehmet Cemal; Nazıroğlu, Mustafa

    2016-09-01

    An excessive production of reactive oxygen substances (ROS) and reduced antioxidant defence systems resulting from electromagnetic radiation (EMR) exposure may lead to oxidative brain and liver damage and degradation of membranes during pregnancy and development of rat pups. We aimed to investigate the effects of Wi-Fi-induced EMR on the brain and liver antioxidant redox systems in the rat during pregnancy and development. Sixteen pregnant rats and their 48 newborns were equally divided into control and EMR groups. The EMR groups were exposed to 2.45GHz EMR (1h/day for 5 days/week) from pregnancy to 3 weeks of age. Brain cortex and liver samples were taken from the newborns between the first and third weeks. In the EMR groups, lipid peroxidation levels in the brain and liver were increased following EMR exposure; however, the glutathione peroxidase (GSH-Px) activity, and vitamin A, vitamin E and β-carotene concentrations were decreased in the brain and liver. Glutathione (GSH) and vitamin C concentrations in the brain were also lower in the EMR groups than in the controls; however, their concentrations did not change in the liver. In conclusion, Wi-Fi-induced oxidative stress in the brain and liver of developing rats was the result of reduced GSH-Px, GSH and antioxidant vitamin concentrations. Moreover, the brain seemed to be more sensitive to oxidative injury compared to the liver in the development of newborns.

  1. Boron deprivation decreases liver S-adenosylmethionine and spermidine and increases plasma homocysteine and cysteine in rats.

    PubMed

    Nielsen, Forrest Harold

    2009-01-01

    Two experiments were conducted with weanling Sprague-Dawley rats to determine whether changes in S-adenosylmethionine utilization or metabolism contribute to the diverse responses to boron deprivation. In both experiments, four treatment groups of 15 male rats were fed ground corn-casein based diets that contained an average of 0.05 mg (experiment 1) or 0.15 mg (experiment 2) boron/kg. In experiment 2, some ground corn was replaced by sucrose and fructose to increase oxidative stress. The dietary variables were supplemental 0 (boron-deprived) or 3 (boron-adequate) mg boron/kg and different fat sources (can affect the response to boron) of 75 g corn oil/kg or 65 g fish (menhaden) oil/kg plus 10 linoleic acid/kg. When euthanized at age 20 (experiment 1) and 18 (experiment 2) weeks, rats fed the low-boron diet were considered boron-deprived because they had decreased boron concentrations in femur and kidney. Boron deprivation regardless of dietary oil increased plasma cysteine and homocysteine and decreased liver S-adenosylmethionine, S-adenosylhomocysteine, and spermidine. Plasma concentration of 8-iso-prostaglandin F2alpha (indicator of oxidative stress) was not affected by boron, but was decreased by feeding fish oil instead of corn oil. Fish oil instead of corn oil decreased S-adenosylmethionine, increased spermidine, and did not affect S-adenosylhomocysteine concentrations in liver. Additionally, fish oil versus corn oil did not affect plasma homocysteine in experiment 1, and slightly increased it in experiment 2. The findings suggest that boron is bioactive through affecting the formation or utilization of S-adenosylmethionine. Dietary fatty acid composition also affects S-adenosylmethionine formation or utilization, but apparently through a mechanism different from that of boron.

  2. Age-dependent increase of etheno-DNA-adducts in liver and brain of ROS overproducing OXYS rats

    SciTech Connect

    Nair, Jagadeesan; Sinitsina, Olga; Vasunina, Elena A.; Nevinsky, Georgy A.; Laval, Jacques; Bartsch, Helmut . E-mail: h.bartsch@dkfz.de

    2005-10-21

    Reactive oxygen species (ROS) and lipid peroxidation (LPO) play a role in aging and degenerative diseases. To correlate oxidative stress and LPO-derived DNA damage, we determined etheno-DNA-adducts in liver and brain from ROS overproducing OXYS rats in comparison with age-matched Wistar rats. Liver DNA samples from 3- and 15-month-old OXYS and Wistar rats were analyzed for 1,N {sup 6}-ethenodeoxyadenosine ({epsilon}dA) and 3,N {sup 4}-ethenodeoxycytidine ({epsilon}dC) by immunoaffinity/{sup 32}P-postlabelling. While {epsilon}dA and {epsilon}dC levels were not different in young rats, adduct levels were significantly higher in old OXYS rats when compared to old Wistar or young OXYS rats. Frozen rat brain sections were analyzed for {epsilon}dA by immunostaining of nuclei. Brains from old OXYS rats accumulated {epsilon}dA more frequently than age-matched Wistar rats. Our results demonstrate increased LPO-induced DNA damage in organs of OXYS rats which correlates with their known shorter life-span and elevated frequency of chronic degenerative diseases.

  3. Ethanolic extract of Taheebo attenuates increase in body weight and fatty liver in mice fed a high-fat diet.

    PubMed

    Choi, Won Hee; Um, Min Young; Ahn, Jiyun; Jung, Chang Hwa; Park, Myung Kyu; Ha, Tae Youl

    2014-10-08

    We evaluated whether intake of an ethanolic extract of Taheebo (TBE) from Tabebuia avellanedae protects against body weight increase and fat accumulation in mice with high-fat diet (HFD)-induced obesity. Four-week old male C57BL/6 mice were fed a HFD (25% fat, w/w) for 11 weeks. The diet of control (HFD) mice was supplemented with vehicle (0.5% sodium carboxymethyl cellulose by gavage); the diet of experimental (TBE) mice was supplemented with TBE (150 mg/kg body weight/day by gavage). Mice administered TBE had significantly reduced body weight gain, fat accumulation in the liver, and fat pad weight, compared to HFD mice. Reduced hypertrophy of fat cells was also observed in TBE mice. Mice administered TBE also showed significantly lower serum levels of triglycerides, insulin, and leptin. Lipid profiles and levels of mRNAs and proteins related to lipid metabolism were determined in liver and white adipose tissue of the mice. Expression of mRNA and proteins related to lipogenesis were decreased in TBE-administered mice compared to mice fed HFD alone. These results suggest that TBE inhibits obesity and fat accumulation by regulation of gene expression related to lipid metabolism in HFD-induced obesity in mice.

  4. Sugars Increase Non-Heme Iron Bioavailability in Human Epithelial Intestinal and Liver Cells

    PubMed Central

    Christides, Tatiana; Sharp, Paul

    2013-01-01

    Previous studies have suggested that sugars enhance iron bioavailability, possibly through either chelation or altering the oxidation state of the metal, however, results have been inconclusive. Sugar intake in the last 20 years has increased dramatically, and iron status disorders are significant public health problems worldwide; therefore understanding the nutritional implications of iron-sugar interactions is particularly relevant. In this study we measured the effects of sugars on non-heme iron bioavailability in human intestinal Caco-2 cells and HepG2 hepatoma cells using ferritin formation as a surrogate marker for iron uptake. The effect of sugars on iron oxidation state was examined by measuring ferrous iron formation in different sugar-iron solutions with a ferrozine-based assay. Fructose significantly increased iron-induced ferritin formation in both Caco-2 and HepG2 cells. In addition, high-fructose corn syrup (HFCS-55) increased Caco-2 cell iron-induced ferritin; these effects were negated by the addition of either tannic acid or phytic acid. Fructose combined with FeCl3 increased ferrozine-chelatable ferrous iron levels by approximately 300%. In conclusion, fructose increases iron bioavailability in human intestinal Caco-2 and HepG2 cells. Given the large amount of simple and rapidly digestible sugars in the modern diet their effects on iron bioavailability may have important patho-physiological consequences. Further studies are warranted to characterize these interactions. PMID:24340076

  5. Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors.

    PubMed

    Gianfrancesco, Milena A; Acuna, Brigid; Shen, Ling; Briggs, Farren B S; Quach, Hong; Bellesis, Kalliope H; Bernstein, Allan; Hedstrom, Anna K; Kockum, Ingrid; Alfredsson, Lars; Olsson, Tomas; Schaefer, Catherine; Barcellos, Lisa F

    2014-01-01

    To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20s demonstrated a linear relationship with MS (p-trend=9.60×10(-4)), and a twofold risk of MS for females with a BMI≥30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles. Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  6. Pediatric Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Delvin, Edgard; Patey, Natasha; Dubois, Josée; Henderson, Melanie; Lévy, Émile

    2015-01-01

    Summary The rapidly increasing prevalence of childhood obesity and its associated co-morbidities such as hypertriglyceridemia, hyper-insulinemia, hypertension, early atherosclerosis, metabolic syndrome, and non-alcoholic fatty liver disease are major public health concerns in many countries. Therefore the trends in child and adolescent obesity should be closely monitored over time, as in the near future, we may anticipate a major increase of young adults with the stigmata of the metabolic syndrome, and of the related non-alcoholic fatty liver disease (NAFLD), that may lead to non-alcoholic steatohepatitis. PMID:28356817

  7. Increased risk of childhood acute lymphoblastic leukemia (ALL) by prenatal and postnatal exposure to high voltage power lines: a case control study in Isfahan, Iran.

    PubMed

    Tabrizi, Maral Mazloomi; Bidgoli, Sepideh Arbabi

    2015-01-01

    Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies, accounting for one fourth of all childhood cancer cases. Exposure to environmental factors around the time of conception or pregnancy can increase the risk of ALL in the offspring.This study aimed to evaluted the role of prenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL.This cross-sectional case control study was carried out on 22 cases and 100 controls who were born and lived in low socioeconomic families in Isfahan and hospitalized for therapeutic purposes in different hospitals from 2013-2014.With regard to the underlying risk factors, familial history and parental factors were noted but in this age, socioeonomic and zonal matched case control study, prenatal and childhood exposure to high voltage power lines was considered as the most important environmental risk factors of ALL (p=0.006, OR=3.651, CI 95%, 1.692-7.878). As the population was of low socioeconomic background, use of mobiles, computers and microwave was negligible. Moreover prenatal and postnatal exposure to indoor electrically charged objects was not determined to be a significant environmental factor. Thus, pre and post natal exposure to high voltage power lines and living in pollutant regions as well as familial influence could be described as risk factors of ALL for the first time in a low socioeconomic status Iranian population.

  8. Low Measured Hepatic Artery Flow Increases Rate of Biliary Strictures in Deceased Donor Liver Transplantation: An Age-Dependent Phenomenon.

    PubMed

    Kim, Peter T W; Fernandez, Hoylan; Gupta, Amar; Saracino, Giovanna; Ramsay, Michael; McKenna, Gregory J; Testa, Giuliano; Anthony, Tiffany; Onaca, Nicholas; Ruiz, Richard M; Klintmalm, Goran B

    2017-02-01

    This study was conducted to determine effect of lower measured hepatic arterial (HA) flow (<400 mL/min) on biliary complications and graft survival after deceased donor liver transplantation. Hepatic artery is the main blood supply to bile duct and lack of adequate HA flow is thought to be a risk factor for biliary complications. A retrospective review of 1300 patients who underwent deceased donor liver transplantation was performed. Patients with arterial complications were excluded to eliminate potential contribution to biliary complications from HA thrombosis. Patients were divided into low (<400 mL/min; N = 201) and high (≥400 mL/min; N = 1099) HA flow groups. Incidence of biliary complications and graft survival were analyzed. HA flows less than 400 mL/min were associated with increased rate of biliary strictures in younger donors (<50 years old), and in patients with duct-to-duct anastomoses (P = 0.028). Lower HA flows were associated with decreased graft survival (P = 0.013). Donor older than 50 years was associated with increased rate of biliary strictures (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.14-2.45; P = 0.0085) and graft failure (HR, 1.68; 95% CI, 1.35-2.1; P <0.0001) on multivariate analyses. HA flow less than 400 mL/min was associated with biliary strictures (HR, 1.53; 95% CI, 1.04-2.24; P = 0.0297) on univariate analysis only. HA flow less than 400 mL/min was associated with higher rate of biliary strictures in younger donors with duct-to-duct reconstruction and lower graft survival. A consideration should be given to increase the intraoperative HA flow to prevent biliary strictures in such patients.

  9. I148M variant in PNPLA3 reduces central adiposity and metabolic disease risks while increasing nonalcoholic fatty liver disease.

    PubMed

    Park, Jin-Ho; Cho, BeLong; Kwon, Hyuktae; Prilutsky, Daria; Yun, Jae Moon; Choi, Ho Chun; Hwang, Kyu-Baek; Lee, In-Hee; Kim, Jong-Il; Kong, Sek Won

    2015-12-01

    The I148M variant because of the substitution of C to G in PNPLA3 (rs738409) is associated with the increased risk of nonalcoholic fatty liver disease (NAFLD). In liver, I148M variant reduces hydrolytic function of PNPLA3, which results in hepatic steatosis; however, its association with the other clinical phenotype such as adiposity and metabolic diseases is not well established. To identify the impact of I148M variant on clinical risk factors of NAFLD, we recruited 1363 generally healthy Korean males after excluding alcoholic and secondary causes of hepatic steatosis. Central adiposity was assessed by computed tomography, and hepatic steatosis was evaluated by abdominal ultrasonography. The participants were predominantly middle-aged (49.0 ± 7.1 years; range 30-60 years), and the frequency of NAFLD was 44.2%. The rs738409-G allele carriers had a 1.19-fold increased risk for NAFLD (minor allele frequency 0.43; allelic odds ratio 1.38; P = 4.3 × 10(-5) ). Interestingly, the rs738409 GG carriers showed significantly lower levels of visceral and subcutaneous adiposity (P < 0.001 and = 0.015, respectively), BMI (P < 0.001), triglycerides (P < 0.001) and insulin resistance (P = 0.002) compared to CC carriers. These negative associations between clinical risk factors and rs738409-G dosage were more prominent in non-NAFLD group compared to those in NAFLD group. The I148M variant, although increasing the risk of NAFLD, was associated with reduced levels of central adiposity, BMI, serum triglycerides and insulin resistance, suggesting differential roles in fat storage and distribution according to cell types and metabolic status. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Adenovirus 36 Attenuates Weight Loss from Exercise but Improves Glycemic Control by Increasing Mitochondrial Activity in the Liver

    PubMed Central

    Ye, Michael B.; Park, Sooho; Kim, In-Beom; Nam, Jae-Hwan

    2014-01-01

    Human adenovirus type 36 (Ad36) as an obesity agent induces adiposity by increasing glucose uptake and promoting chronic inflammation in fat tissues; in contrast, exercise reduces total body fat and inflammation. Our objective was to determine the association between Ad36 and the effects of exercise on inflammation and glycemic control. In the human trials (n = 54), Korean children (aged 12–14 years) exercised for 60 min on three occasions each week for 2 months. We compared the body mass index (BMI) Z-scores before and after exercise. C57BL/6 mice were infected with Ad36 and Ad2 as a control, and these mice exercised for 12 weeks postinfection. After the exercise period, we determined the serum parameters and assessed the presence of inflammation and the mitochondrial function in the organs. Ad36-seropositive children who were subjected to a supervised exercise regimen had high BMI Z-scores whereas Ad36-seronegative children had lower scores. Similarly, Ad36-infected mice were resistant to weight loss and exhibited chronic inflammation of their adipose tissues despite frequent exercise. However, Ad36 combined with exercise reduced the levels of serum glucose, nonesterified fatty acids, total cholesterol, and insulin in virus-infected mice. Interestingly, virus infection increased the mitochondrial function in the liver, as demonstrated by the numbers of mitochondria, cytochrome c oxidase activity, and transcription of key mitochondrial genes. Therefore Ad36 counteracts the weight-loss effect of exercise and maintains the chronic inflammatory state, but glycemic control is improved by exercise synergistically because of increased mitochondrial activity in the liver. PMID:25479564

  11. In vivo vitamin C deficiency in guinea pigs increases ascorbate transporters in liver but not kidney and brain.

    PubMed

    Søgaard, Ditte; Lindblad, Maiken M; Paidi, Maya D; Hasselholt, Stine; Lykkesfeldt, Jens; Tveden-Nyborg, Pernille

    2014-07-01

    Moderate vitamin C (vitC) deficiency (plasma concentrations less than 23 μmol/L) affects as much as 10% of adults in the Western World and has been associated with an increased mortality in disease complexes such as cardiovascular disease and the metabolic syndrome. The distribution of vitC within the body is subjected to complex and nonlinear pharmacokinetics and largely depends on the sodium-dependent vitC-specific transporters, sodium-dependent vitamin C transporter 1 (SVCT1) and sodium-dependent vitamin C transporter 2 (SVCT2). Although currently not established, it is likely to expect that a state of deficiency may affect the expression of these transporters to preserve vitC concentrations in specific target tissues. We hypothesized that diet-induced states of vitC deficiency lead to alterations in the messenger RNA (mRNA) and/or protein expression of vitC transporters, thereby regulating vitC tissue distribution. Using guinea pigs as a validated model, this study investigated the effects of a diet-induced vitC deficiency (100 mg vitC/kg feed) or depletion (0 mg vitC/kg feed) on the expression of transporters SVCT1 and SVCT2 in selected tissues and the transport from plasma to cerebrospinal fluid (CSF). In deficient animals, SVCT1 was increased in the liver, whereas a decreased SVCT1 expression but increased SVCT2 mRNA in livers of depleted animals suggests a shift in transporter expression as response to the diet. In CSF, a constant plasma:CSF ratio shows unaltered vitC transport irrespective of dietary regime. The study adds novel information to the complex regulation maintaining vitC homeostasis in vivo during states of deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Rural to urban migration is associated with increased prevalence of childhood wheeze in a Latin-American city.

    PubMed

    Rodriguez, Alejandro; Vaca, Maritza G; Chico, Martha E; Rodrigues, Laura C; Barreto, Mauricio L; Cooper, Philip J

    2017-01-01

    The urbanisation process has been associated with increases in asthma prevalence in urban and rural areas of low-income and middle-income countries (LMICs). However, although rural to urban migration and migration between cities are considered important determinants of this process, few studies have evaluated the effects of internal migration on asthma in urban populations of LMICs. The present study evaluated the effects of internal migration on the prevalence of wheeze in an urban area of Latin America. We did a cross-sectional analysis of 2510 schoolchildren living in the city of Esmeraldas, Ecuador. Logistic regression was used to analyse associations between childhood wheeze and different aspects of migration among schoolchildren. 31% of schoolchildren were migrants. Rural to urban migrants had a higher prevalence of wheeze, (adj.OR=2.01,95% CI1.30 to 3.01, p=0.001) compared with non-migrants. Age of migration and time since migration were associated with wheeze only for rural to urban migrants but not for urban to urban migrants. Children who had migrated after 3 years of age had a greater risk of wheeze (OR 2.51, 95% CI 1.56 to 3.97, p=0.001) than non-migrants while migrants with less than 5 years living in the new residence had a higher prevalence of wheeze than non-migrants (<3 years: OR=2.34, 95% CI 1.26 to 4.33, p<0.007 and 3-5 years: OR=3.03, 95% CI 1.49 to 6.15, p<0.002). Our study provides evidence that rural to urban migration is associated with an increase in the prevalence of wheeze among schoolchildren living in a Latin-American city. Age of migration and time since migration were important determinants of wheeze only among migrants from rural areas. A better understanding of the social and environmental effects of internal migration could improve our understanding of the causes of the increase in asthma and differences in prevalence between urban and rural populations.

  13. Rural to urban migration is associated with increased prevalence of childhood wheeze in a Latin-American city

    PubMed Central

    Rodriguez, Alejandro; Vaca, Maritza G; Chico, Martha E; Rodrigues, Laura C; Barreto, Mauricio L; Cooper, Philip J

    2017-01-01

    Introduction The urbanisation process has been associated with increases in asthma prevalence in urban and rural areas of low-income and middle-income countries (LMICs). However, although rural to urban migration and migration between cities are considered important determinants of this process, few studies have evaluated the effects of internal migration on asthma in urban populations of LMICs. The present study evaluated the effects of internal migration on the prevalence of wheeze in an urban area of Latin America. Methods We did a cross-sectional analysis of 2510 schoolchildren living in the city of Esmeraldas, Ecuador. Logistic regression was used to analyse associations between childhood wheeze and different aspects of migration among schoolchildren. Results 31% of schoolchildren were migrants. Rural to urban migrants had a higher prevalence of wheeze, (adj.OR=2.01,95% CI1.30 to 3.01, p=0.001) compared with non-migrants. Age of migration and time since migration were associated with wheeze only for rural to urban migrants but not for urban to urban migrants. Children who had migrated after 3 years of age had a greater risk of wheeze (OR 2.51, 95% CI 1.56 to 3.97, p=0.001) than non-migrants while migrants with less than 5 years living in the new residence had a higher prevalence of wheeze than non-migrants (<3 years: OR=2.34, 95% CI 1.26 to 4.33, p<0.007 and 3–5 years: OR=3.03, 95% CI 1.49 to 6.15, p<0.002). Conclusions Our study provides evidence that rural to urban migration is associated with an increase in the prevalence of wheeze among schoolchildren living in a Latin-American city. Age of migration and time since migration were important determinants of wheeze only among migrants from rural areas. A better understanding of the social and environmental effects of internal migration could improve our understanding of the causes of the increase in asthma and differences in prevalence between urban and rural populations. PMID:28883931

  14. Increased susceptibility to liver injury after hemorrhagic shock in rats chronically fed ethanol: role of nuclear factor-kappa B, interleukin-6, and granulocyte colony-stimulating factor.

    PubMed

    Ono, Masafumi; Yu, Bi; Hardison, Edith G; Mastrangelo, Mary-Ann A; Tweardy, David J

    2004-06-01

    Chronic ethanol use preceding severe trauma and hemorrhagic shock (HS) is associated with an increased incidence of multiorgan failure (MOF) and death; however, the molecular basis for this increased susceptibility is unknown. We previously demonstrated that production of interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF), mediated by nuclear factor-kappa B (NF-kappa B), each make essential contributions to organ injury and inflammation in a rodent model of controlled HS, and we proposed in this study to examine the hypothesis that the increased susceptibility to MOF after shock/trauma in the setting of chronic ethanol use is due to an exaggerated activation of NF-kappa B and production of these proinflammatory cytokines. We observed increased HS-induced liver injury 4 h after resuscitation in rats fed the ethanol-containing Lieber-DeCarli liquid diet for 8 weeks compared with rats fed the control liquid diet (3-fold increase in serum alanine aminotransferase [ALT], P = 0.008, and 2-fold increase in focal liver necrosis, P = 0.005). The increased liver injury in the ethanol-fed HS rats was accompanied by a 70% increase in liver NF-kappa B activation (P < 0.05), a 3- to 5-fold increase in hepatocyte and Kupffer cell production of IL-6 and G-CSF (P < 0.05 for each), and a 2-fold increase in neutrophil infiltration (P < 0.005) compared with the control diet-fed HS rats. Thus, increased susceptibility to HS-induced liver injury in the setting of chronic ethanol use may be mediated, at least in part, by increased NF-kappa B activation resulting in increased local production of IL-6 and G-CSF and increased infiltration of neutrophils, which can damage liver cells directly and contribute to impaired sinusoidal blood flow.

  15. Increasing Early Childhood Educators' Use of Communication-Facilitating and Language-Modelling Strategies: Brief Speech and Language Therapy Training

    ERIC Educational Resources Information Center

    McDonald, David; Proctor, Penny; Gill, Wendy; Heaven, Sue; Marr, Jane; Young, Jane

    2015-01-01

    Intensive Speech and Language Therapy (SLT) training courses for Early Childhood Educators (ECEs) can have a positive effect on their use of interaction strategies that support children's communication skills. The impact of brief SLT training courses is not yet clearly understood. The aims of these two studies were to assess the impact of a brief…

  16. Online Course Increases Nutrition Professionals' Knowledge, Skills, and Self-Efficacy in Using an Ecological Approach to Prevent Childhood Obesity

    ERIC Educational Resources Information Center

    Stark, Christina M.; Graham-Kiefer, Meredith L.; Devine, Carol M.; Dollahite, Jamie S.; Olson, Christine M.

    2011-01-01

    Objective: To assess the impact of an online continuing education course on the knowledge, skills, and self-efficacy of nutrition professionals to use an ecological approach to prevent childhood obesity. Design: Quasi-experimental design using intervention and delayed intervention comparison groups with pre/post-course assessments. Setting: Online…

  17. An Intervention to Increase Early Childhood Staff Capacity for Promoting Children's Social-Emotional Development in Preschool Settings

    ERIC Educational Resources Information Center

    Green, Beth L.; Malsch, Anna M.; Kothari, Brianne Hood; Busse, Jessica; Brennan, Eileen

    2012-01-01

    This article describes the development, implementation, and outcomes of a pilot intervention designed to enhance preschool programs' ability to support children's social-emotional development. Working with two Head Start programs, the intervention included (1) restructuring existing early childhood mental health consultation services; (2) engaging…

  18. Increasing Early Childhood Educators' Use of Communication-Facilitating and Language-Modelling Strategies: Brief Speech and Language Therapy Training

    ERIC Educational Resources Information Center

    McDonald, David; Proctor, Penny; Gill, Wendy; Heaven, Sue; Marr, Jane; Young, Jane

    2015-01-01

    Intensive Speech and Language Therapy (SLT) training courses for Early Childhood Educators (ECEs) can have a positive effect on their use of interaction strategies that support children's communication skills. The impact of brief SLT training courses is not yet clearly understood. The aims of these two studies were to assess the impact of a brief…

  19. Online Course Increases Nutrition Professionals' Knowledge, Skills, and Self-Efficacy in Using an Ecological Approach to Prevent Childhood Obesity

    ERIC Educational Resources Information Center

    Stark, Christina M.; Graham-Kiefer, Meredith L.; Devine, Carol M.; Dollahite, Jamie S.; Olson, Christine M.

    2011-01-01

    Objective: To assess the impact of an online continuing education course on the knowledge, skills, and self-efficacy of nutrition professionals to use an ecological approach to prevent childhood obesity. Design: Quasi-experimental design using intervention and delayed intervention comparison groups with pre/post-course assessments. Setting: Online…

  20. An Intervention to Increase Early Childhood Staff Capacity for Promoting Children's Social-Emotional Development in Preschool Settings

    ERIC Educational Resources Information Center

    Green, Beth L.; Malsch, Anna M.; Kothari, Brianne Hood; Busse, Jessica; Brennan, Eileen

    2012-01-01

    This article describes the development, implementation, and outcomes of a pilot intervention designed to enhance preschool programs' ability to support children's social-emotional development. Working with two Head Start programs, the intervention included (1) restructuring existing early childhood mental health consultation services; (2) engaging…

  1. Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction.

    PubMed

    Qian, Guoqing; Tang, Lili; Lin, Shuhan; Xue, Kathy S; Mitchell, Nicole J; Su, Jianjia; Gelderblom, Wentzel C; Riley, Ronald T; Phillips, Timothy D; Wang, Jia-Sheng

    2016-09-01

    Dietary co-exposure to aflatoxin B1 (AFB1) and fumonisin B1 (FB1) and their interaction on hepatocellular carcinogenesis is of particular concern in toxicology and public health. In this study we evaluated the liver preneoplastic effects of single and sequential dietary exposure to AFB1 and FB1 in the F344 rat carcinogenesis model. Serum biochemical alterations, liver histopathological changes, and the formation of liver glutathione S transferase positive (GST-P+) foci were the major outcome parameters examined. Compared to the AFB1-only treatment, the FB1-only treatment induced less dysplasia, and more apoptosis and mitoses. Sequential AFB1 and FB1 treatment lead to increased numbers of dysplasia, apoptosis and foci of altered hepatocytes, as compared to either mycotoxin treatment alone. More importantly, sequential exposure to AFB1 and FB1 synergistically increased the numbers of liver GTP-P+ foci by approximately 7.3-and 12.9-fold and increased the mean sizes of GST-P+ foci by 6- and 7.5-fold, respectively, as compared to AFB1- or FB1-only treatment groups. In addition, liver ALT and AST levels were significantly increased after sequential treatment as compared to single treatment groups. The results demonstrate the interactive effect of dietary AFB1 and FB1 in inducing liver GST-P+ foci formation and provide information to model future intervention studies.

  2. Ultrasonic characterization of the nonlinear properties of canine livers by measuring shear wave speed and axial strain with increasing portal venous pressure.

    PubMed

    Rotemberg, Veronica; Byram, Brett; Palmeri, Mark; Wang, Michael; Nightingale, Kathryn

    2013-07-26

    Elevated hepatic venous pressure is the primary source of complications in advancing liver disease. Ultrasound imaging is ideal for potential noninvasive hepatic pressure measurements as it is widely used for liver imaging. Specifically, ultrasound based stiffness measures may be useful for clinically monitoring pressure, but the mechanism by which liver stiffness increases with hepatic pressure has not been well characterized. This study is designed to elucidate the nonlinear properties of the liver during pressurization by measuring both hepatic shear wave speed (SWS) and strain with increasing pressure. Tissue deformation during hepatic pressurization was tracked in 8 canine livers using successively acquired 3-D B-mode volumes and compared with concurrently measured SWS. When portal venous pressure was increased from clinically normal (0-5mmHg) to pressures representing highly diseased states at 20mmHg, the liver was observed to expand with axial strain measures up to 10%. At the same time, SWS estimates were observed to increase from 1.5-2m/s at 0-5mmHg (baseline) to 3.25-3.5m/s at 20mmHg. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Introduction to Childhood Studies

    ERIC Educational Resources Information Center

    Kehily, Mary Jane, Ed.

    2004-01-01

    Educationalists and social scientists are increasingly interested in childhood as a distinct social category, and Childhood Studies is now a recognized area of research and analysis. This book brings together the key themes of Childhood Studies in a broad and accessible introduction for students and practitioners working in this field.…

  4. The Synthetic Triterpenoid RTA 405 (CDDO-EA) Halts Progression of Liver Fibrosis and Reduces Hepatocellular Carcinoma Size Resulting in Increased Survival in an Experimental Model of Chronic Liver Injury

    PubMed Central

    Getachew, Yonas; Cusimano, Frank A.; Gopal, Purva; Reisman, Scott A.; Shay, Jerry W.

    2016-01-01

    Patients with cirrhosis have an increased risk of developing liver cancer and a higher rate of mortality. Cirrhosis currently has no known cure, and patients may benefit from new agents aimed at alleviating their complications and slowing down the rate of disease progression. Therefore, the effects of the orally bioavailable synthetic triterpenoid 2-cyano-3,12-dioxooleana- 1,9(11)-dien-28-oate-ethyl amide (CDDO-EA, RTA 405), which has potent antioxidative and antiinflammatory properties, was evaluated in a chronic carbon tetrachloride (CCl4)-induced model of liver cirrhosis and hepatocellular carcinoma (HCC). Mice were injected with CCl4 (to induce fibrosis and cirrhosis) or placebo biweekly for 12 weeks followed by CDDO-EA in the diet for 18 weeks with continued biweekly injections of CCl4. Chronic CCl4 administration resulted in cirrhosis, ascites, and HCC formation, associated with increased serum transforming growth factor-β1, hepatic hydroxyproline content, and increased serum bilirubin. CDDO-EA, whose administration commenced after establishment of liver fibrosis, decreased liver fibrosis progression, serum bilirubin, ascites, and HCC formation and markedly increased overall survival. CDDO-EA also attenuated -TNFα (tumor necrosis factor-α), α-SMA (alpha smooth muscle actin), augmented -IL-10 levels, and improved histologic and serologic markers of fibrosis. Conclusions: CDDO-EA mitigates the progression of liver fibrosis induced by chronic CCl4 administration, which is associated with the induction of antifibrogenic genes and suppression of profibrogenic genes. PMID:26443840

  5. Increased incidence of liver cancer after successful DAA treatment of chronic hepatitis C: Fact or fiction?

    PubMed

    Alberti, Alfredo; Piovesan, Sara

    2017-06-01

    Therapy of hepatitis C has been revolutionized by Direct Antiviral Agents. These drugs are safe and efficacious in all infected patients, including those with advanced, or decompensated cirrhosis, and are currently largely used in such cases in clinical practice worldwide. It was therefore cause of great concern the publication of two reports suggesting that treatment with DAAs could increase the risk of hepatocellular carcinoma in cirrhotic patients, particularly in those receiving antiviral therapy after having been cured for an HCC. These reports have generated a great and controversial debate and have been followed by a series of other publications not confirming such increased risk. This article summarizes published studies assessing the relation between DAA therapy and HCC in two different clinical setting: HCC recurrence in patients with an history of cured HCC and "de novo" HCC occurrence in patients without previous HCC. Rates of HCC recurrence after DAAs were extremely variable in different studies, reflecting great heterogeneity of this clinical setting. Data on "de novo" HCC incidence were more homogeneous and suggest that treatment with DAAs is not modifying the risk of developing HCC in the first 6-12 months. The possibility that treatment with DAAs may favour tumour growth and spread in individual patients with active HCC foci is suggested by some observations but remains unproven. There is clearly a need for prospective studies designed to better define these issues. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

    PubMed Central

    Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

    2006-01-01

    CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (P<0.05) of CYP2B6 protein levels was observed in all regions tested (caudate, putamen, hippocampus, cerebellum, brain stem and frontal cortex) ranging from 2-fold to 150-fold. CYP2B6 expression was induced in specific cells, such as frontal cortical pyramidal cells and thalamic neurons. In conclusion, chronic phenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

  7. Advanced glycation end products promote ChREBP expression and cell proliferation in liver cancer cells by increasing reactive oxygen species.

    PubMed

    Chen, Hanbei; Li, Yakui; Zhu, Yemin; Wu, Lifang; Meng, Jian; Lin, Ning; Yang, Dianqiang; Li, Minle; Ding, WenJin; Tong, Xuemei; Su, Qing

    2017-08-01

    The aim of the study was to elucidate the mechanism by which advanced glycation end products (AGEs) promote cell proliferation in liver cancer cells.We treated liver cancer HepG2 cells with 200 mg/L AGEs or bovine serum albumin (BSA) and assayed for cell viability, cell cycle, and apoptosis. We performed real-time PCR and Western blot analysis for RNA and protein levels of carbohydrate responsive element-binding protein (ChREBP) in AGEs- or BSA-treated HepG2 cells. We analyzed the level of reactive oxygen species (ROS) in HepG2 cells treated with AGEs or BSA.We found that increased S-phase cell percentage and decreased apoptosis contributed to AGEs-induced liver cancer cell proliferation. Real-time PCR and Western blot analysis showed that AGEs stimulated RNA and protein levels of ChREBP, a transcription factor promoting glycolysis and maintaining cell proliferation in liver cancer cells. Intriguingly, the level of ROS was higher in AGEs-treated liver cancer cells. Treating liver cancer cells with antioxidant N-acetyl cystein (NAC) partly blocked AGEs-induced ChREBP expression and cell proliferation.Our results suggest that the AGEs-ROS-ChREBP pathway plays a critical role in promoting ChREBP expression and liver cancer cell proliferation.

  8. Increase in de novo food allergies after pediatric liver transplantation: tacrolimus vs. cyclosporine immunosuppression.

    PubMed

    Lebel, Marie-Jeanne; Chapdelaine, Hugo; Paradis, Louis; Des Roches, Anne; Alvarez, Fernando

    2014-11-01

    Post-TAFA is an uncommon but serious complication of organ transplantation. This study aimed to compare the incidence of FA in CsA and tacrolimus-treated children following OLT and identify risk factors. The medical charts of all patients who underwent OLT at our institution were reviewed. Between 1985 and 2010, 218 OLTs were performed on 188 pediatric recipients, of which 154 were included in the study. Three patients (3%) of the 102 receiving CsA developed FA, compared with nine (17%) in the 52 tacrolimus-treated patients, the latter exceeding general population reported FA prevalence (RR 5.88; 95% CI: 1.66-20.81). All TAFA cases underwent transplantation before the age of three with an incidence of 29% (9/31) in the tacrolimus-treated children in comparison with 7% (3/41) in the CsA group (RR 3.97; 95% CI: 1.17-13.45). Eosinophilia was present in 81% of children receiving tacrolimus compared with 54% in the CsA group (p = 0.002). We observed a statistically significant increase incidence of FA in tacrolimus-treated children following an OLT and those under the age of three are particularly vulnerable. The underlying process is still unknown and probably multifactorial. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Increased oxygen radical-dependent inactivation of metabolic enzymes by liver microsomes after chronic ethanol consumption

    SciTech Connect

    Dicker, E.; Cederbaum, A.I. )

    1988-10-01

    Enzymatic and nonenzymatic mixed-function oxidase systems have been shown to generate an oxidant that catalyzes the inactivation of glutamine synthetase and other metabolic enzymes. Recent studies have shown that microsomes isolated from rats chronically fed ethanol generate reactive oxygen intermediates at elevated rates compared with controls. Microsomes from rats fed ethanol were found to be more effective than control microsomes in catalyzing the inactivation of enzymes added to the incubation system. The enzymes studied were alcohol dehydrogenase, lactic dehydrogenase, and pyruvate kinase. The inactivation process by both types of microsomal preparations was sensitive to catalase and glutathione plus glutathione peroxidase, but was not affected by superoxide dismutase or hydroxyl radical scavengers. Iron was required for the inactivation of added enzymes; microsomes from the rats fed ethanol remained more effective than control microsomes in catalyzing the inactivation of enzymes in the absence or presence of several ferric complexes. The inactivation of enzymes was enhanced by the addition of menadione or paraquat to the microsomes, and rates of inactivation were higher with the microsomes from the ethanol-fed rats. The enhanced generation of reactive oxygen intermediates and increased inactivation of enzymes by microsomes may contribute toward the hepatotoxic effects associated with ethanol consumption.

  10. Increased incidence and altered risk demographics of childhood lead poisoning: predicting the impacts of the CDC’s 5 µg/dL reference value in Massachusetts (USA).

    PubMed

    Handler, Phoebe; Brabander, Daniel

    2012-10-30

    In May 2012, the CDC adopted a new sliding scale reference value for childhood lead poisoning, reducing the former 10 μg/dL benchmark by half. Using Massachusetts (MA) as a model state, we estimated the change in the population of 9-47 month-olds at risk for lead poisoning. We then examined the impact of the 5 µg/dL reference value on the demographic characteristics of lead risk in MA communities. We find that the new CDC benchmark will lead to a 1470% increase in childhood lead poisoning cases among 9-47 month-olds in MA, with nearly 50% of the examined communities experiencing an increased prevalence of lead poisoning. Further, the top 10 MA communities with BLLs ≥5 μg/dL have significantly fewer foreign-born residents and significantly larger white populations than the highest risk communities formerly identified by the MA Childhood Lead Poisoning Prevention Program. The CDC's new 5 μg/dL lead poisoning benchmark will drastically increase the number of children with elevated BLLs and alter the distribution and demographics high-risk communities in MA.

  11. Iron overload alters glucose homeostasis, causes liver steatosis, and increases serum triacylglycerols in rats.

    PubMed

    Silva, Maísa; Silva, Marcelo E; de Paula, Heberth; Carneiro, Cláudia Martins; Pedrosa, Maria Lucia

    2008-06-01

    The objective of this study was to investigate the effect of iron overload with a hyperlipidemic diet on the histologic feature of hepatic tissue, the lipid and glycemic serum profiles, and the markers of oxidative damage and stress in a rat model. Twenty-four male Fischer rats, purchased from Experimental Nutrition Laboratory, Federal University of Ouro Preto, were assigned to 4 equal groups, 2 were fed a standard cholesterol-free diet (group C or control and CI or control with iron) containing 8.0% soybean oil and 2 were fed a hyperlipidemic diet (group H or hyperlipidemic and HI or hyperlipidemic with iron) containing 1.0% cholesterol and 25.0% soybean oil. A total of 50 mg of iron was administered to rats in groups CI and HI in 5 equal doses (1 every 3 weeks for a 16-week period) by intraperitoneal injections of 0.1 mL of iron dextran solution (100 g Fe(2+)/L; Sigma, St Louis, Mo). The other rats in groups C and H were treated in a similar manner but with sterile saline (0.1 mL). Irrespective of the diet, iron excess enhanced serum triacylglycerols (P < .05) and reduced serum glucose and glycated hemoglobin levels (P < .05) but did not affect serum cholesterol concentration. Histologic analysis showed steatosis in groups H and to a lesser extent in HI. No significant differences (P > .05) were observed in paraoxonase activities or in serum levels of free or total sulfhydryl radicals, malondialdehyde, or total antioxidants. The findings suggest that iron excess in the rat probably modifies lipid metabolism and, as a consequence, alters glucose homeostasis and increases the level of serum triacylglycerols but not of cholesterol.

  12. Melatonin increases intracellular calcium in the liver, muscle, white adipose tissues and pancreas of diabetic obese rats.

    PubMed

    Agil, A; Elmahallawy, E K; Rodríguez-Ferrer, J M; Adem, A; Bastaki, S M; Al-Abbadi, I; Fino Solano, Y A; Navarro-Alarcón, M

    2015-08-01

    Melatonin, a widespread substance with antioxidant and anti-inflammatory properties, has been found to act as an antidiabetic agent in animal models, regulating the release and action of insulin. However, the molecular bases of this antidiabetic action are unknown, limiting its application in humans. Several studies have recently shown that melatonin can modify calcium (Ca(2+)) in diabetic animals, and Ca(2+) has been reported to be involved in glucose homeostasis. The objective of the present study was to assess whether the antidiabetic effect of chronic melatonin at pharmacological doses is established via Ca(2+) regulation in different tissues in an animal model of obesity-related type 2 diabetes, using Zücker diabetic fatty (ZDF) rats and their lean littermates, Zücker lean (ZL) rats. After the treatments, flame atomic absorption spectrometry was used to determine Ca(2+) levels in the liver, muscle, main types of internal white adipose tissue, subcutaneous lumbar fat, pancreas, brain, and plasma. This study reports for the first time that chronic melatonin administration (10 mg per kg body weight per day for 6 weeks) increases Ca(2+) levels in muscle, liver, different adipose tissues, and pancreas in ZDF rats, although there were no significant changes in their brain or plasma Ca(2+) levels. We propose that this additional peripheral dual action mechanism underlies the improvement in insulin sensitivity and secretion previously documented in samples from the same animals. According to these results, indoleamine may be a potential candidate for the treatment of type 2 diabetes mellitus associated with obesity.

  13. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

  14. Increased Iron Loading Induces Bmp6 Expression in the Non-Parenchymal Cells of the Liver Independent of the BMP-Signaling Pathway

    PubMed Central

    Enns, Caroline A.; Ahmed, Riffat; Wang, Jiaohong; Ueno, Akiko; Worthen, Christal; Tsukamoto, Hidekazu; Zhang, An-Sheng

    2013-01-01

    Bone morphogenetic protein 6 (BMP6) is an essential cytokine for the expression of hepcidin, an iron regulatory hormone secreted predominantly by hepatocytes. Bmp6 expression is upregulated by increased iron-levels in the liver. Both hepatocytes and non-parenchymal liver cells have detectable Bmp6 mRNA. Here we showed that induction of hepcidin expression in hepatocytes by dietary iron is associated with an elevation of Bmp6 mRNA in the non-parenchymal cells of the liver. Consistently, incubation with iron-saturated transferrin induces Bmp6 mRNA expression in isolated hepatic stellate cells, but not in hepatocytes. These observations suggest an important role of the non-parenchymal liver cells in regulating iron-homeostasis by acting as a source of Bmp6. PMID:23565256

  15. Increased oxidative-modifications of cytosolic proteins in 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-exposed rat liver.

    PubMed

    Upreti, Vijay V; Moon, Kwan-Hoon; Yu, Li-Rong; Lee, Insong J; Eddington, Natalie D; Ye, Xiaoying; Veenstra, Timothy D; Song, Byoung-Joon

    2011-01-01

    It is well established that 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) causes acute liver damage in animals and humans. The aim of this study was to identify and characterize oxidative modification and inactivation of cytosolic proteins in MDMA-exposed rats. Markedly increased levels of oxidized and nitrated cytosolic proteins were detected 12 h after the second administration of two consecutive MDMA doses (10 mg/kg each). Comparative 2-DE analysis showed markedly increased levels of biotin-N-methylimide-labeled oxidized cytosolic proteins in MDMA-exposed rats compared to vehicle-treated rats. Proteins in the 22 gel spots of strong intensities were identified using MS/MS. The oxidatively modified proteins identified include anti-oxidant defensive enzymes, a calcium-binding protein, and proteins involved in metabolism of lipids, nitrogen, and carbohydrates (glycolysis). Cytosolic superoxide dismutase was oxidized and its activity significantly inhibited following MDMA exposure. Consistent with the oxidative inactivation of peroxiredoxin, MDMA activated c-Jun N-terminal protein kinase and p38 kinase. Since these protein kinases phosphorylate anti-apoptotic Bcl-2 protein, their activation may promote apoptosis in MDMA-exposed tissues. Our results show for the first time that MDMA induces oxidative-modification of many cytosolic proteins accompanied with increased oxidative stress and apoptosis, contributing to hepatic damage.

  16. Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis

    PubMed Central

    Massart, J; Robin, MA; Noury, F; Fautrel, A; Lettéron, P; Bado, A; Eliat, PA; Fromenty, B

    2012-01-01

    BACKGROUND AND PURPOSE Pentoxifylline is in clinical trials for non-alcoholic fatty liver disease and diabetic nephropathy. Metabolic and hepatic effects of pentoxifylline were assessed in a murine model of obesity and type 2 diabetes. EXPERIMENTAL APPROACH Pentoxifylline (100 mg·kg−1·day−1) was administered for 4 days or 3 weeks in lean and obese/diabetic ob/ob mice. Plasma lipids, glucose, other metabolites and relevant enzymes were measured by standard assays. Hepatic lipids in vivo were assessed with magnetic resonance spectroscopy and by histology. Hepatic extracts were also analysed with RT-PCR and Western blotting. KEY RESULTS Four days of pentoxifylline treatment slightly increased liver lipids in ob/ob mice. After 3 weeks, pentoxifylline exacerbated fatty liver and plasma transaminases in ob/ob mice but did not induce liver steatosis in lean mice. Plasma glucose was highest in fed, but not fasted, ob/ob mice treated with pentoxifylline. During the first 10 min of an oral glucose tolerance test, blood glucose increased more rapidly in pentoxifylline-treated mice. Jejunal expression of glucose transporter 2 isoform was increased in pentoxifylline-treated obese mice. Hepatic activity of carbohydrate response element binding protein (ChREBP) increased after pentoxifylline in ob/ob, but not lean, mice. Hepatic expression of lipogenic enzymes was highest in pentoxifylline-treated ob/ob mice. However, pentoxifylline reduced markers of oxidative stress and inflammation in ob/ob liver. CONCLUSION AND IMPLICATIONS Pentoxifylline exacerbated fatty liver in ob/ob mice through enhanced intestinal glucose absorption, increased postprandial glycaemia and activation of hepatic lipogenesis. Long-term treatment with pentoxifylline could worsen fatty liver in some patients with pre-existing hyperglycaemia. PMID:21740407

  17. A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6.

    PubMed

    De León-Nava, Marco A; Álvarez-Delgado, Carolina; Donis-Maturano, Luis; Hernández-Ruiz, Joselin; Manjarrez-Reyna, Aaron N; Cruz-Avilés, Edgar; Leon-Cabrera, Sonia; Morales-Montor, Jorge; Fragoso, José M; Escobedo, Galileo

    2016-12-01

    We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.

  18. A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6

    PubMed Central

    De León-Nava, Marco A; Álvarez-Delgado, Carolina; Donis-Maturano, Luis; Hernández-Ruiz, Joselin; Manjarrez-Reyna, Aaron N; Cruz-Avilés, Edgar; Leon-Cabrera, Sonia; Morales-Montor, Jorge; Fragoso, José M; Escobedo, Galileo

    2016-01-01

    We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients. PMID:27812602

  19. Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis B.

    PubMed

    Tang, Kuo-Tung; Hung, Wei-Ting; Chen, Yi-Hsing; Lin, Ching-Heng; Chen, Der-Yuan

    2016-03-01

    A few studies showed that long-term methotrexate (MTX) use exacerbates liver fibrosis and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients. We therefore conducted a population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic hepatitis B (CHB)-related cirrhosis among RA patients. We analyzed data from the National Health Insurance Research Database in Taiwan and identified 631 incident cases of RA among CHB patients (358 MTX users and 273 MTX non-users) from January 1, 1998 to December 31, 2007. After a median follow-up of more than 6 years since the diagnosis of CHB, a total of 41 (6.5%) patients developed liver cirrhosis. We did not find an increased risk of liver cirrhosis among CHB patients with long-term MTX use for RA. Furthermore, there was no occurrence of liver cirrhosis among 56 MTX users with a cumulative dose ≧3 grams after 97 months' treatment. In conclusion, our data showed that long-term MTX use is not associated with an increased risk for liver cirrhosis among RA patients with CHB. However, interpretation of the results should be cautious due to potential bias in the cohort.

  20. Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis C

    PubMed Central

    Tang, Kuo-Tung; Chen, Yi-Hsing; Lin, Ching-Heng; Chen, Der-Yuan

    2016-01-01

    A few studies have shown that methotrexate (MTX) use exacerbates liver fibrosis and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients, although the risk is low compared to psoriatics. We therefore conducted a population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic hepatitis C (CHC)-related cirrhosis among RA patients. We analyzed data from the National Health Insurance Research Database in Taiwan and identified 450 incident cases of RA among CHC patients (255 MTX users and 195 MTX non-users) from January 1, 1998 to December 31, 2007. After a median follow-up of more than 5 years since the diagnosis of CHC, a total of 55 (12%) patients developed liver cirrhosis. We did not find an increased risk of liver cirrhosis among CHC patients with long-term MTX use for RA. Furthermore, there was no occurrence of liver cirrhosis among the 43 MTX users with a cumulative dose ≧3 grams after 108 months of treatment. In conclusion, our data showed that long-term MTX use is not associated with an increased risk for liver cirrhosis among RA patients with CHC. However, these results should be interpreted with caution due to potential bias in the cohort. PMID:27609026

  1. Pediatric Non-alcoholic Fatty Liver Disease.

    PubMed

    Uppal, Vikas; Mansoor, Sana; Furuya, Katryn N

    2016-05-01

    Childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly, children are developing complications of obesity including liver disease. In fact, non-alcoholic fatty liver disease is the most common form of chronic liver disease seen in children today. Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease. On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of pediatric non-alcoholic fatty liver disease (NAFLD) has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.

  2. Liver reperfusion-induced decrease in dynamic compliance and increase in airway resistance are ameliorated by preischemic treatment with melatonin through scavenging hydroxyl radicals in rat lungs.

    PubMed

    Yeh, J-H; Su, C-L; Chen, C F; Wang, D; Wang, J-J

    2012-05-01

    Acute lung injury is frequently observed in patients subsequent to liver ischemia and reperfusion (I/R) injury. However, the changes in pulmonary function, eg, lung dynamic compliance (C(dyn)) and airway resistance (RI), are not well understood. We sought to study the alternations in pulmonary function during liver I/R and the protective effects of preischemic treatment with melatonin. Animals were divided into 3 groups: sham-operated, liver I/R, and intraperitoneal (i.p.) pretreatment with melatonin (15 mg/kg). Liver I/R was performed by clamping the hepatic artery and portal vein for 30 minutes followed by releasing for 2 hours. The C(dyn) and RI were studied at baseline and at 2 hours of reperfusion. We assessed the level of pulmonary hydroxyl radicals by methylguanidine (MG) content in the bronchoalveolar lavage fluid (BALF) as well as the liver damage using plasma levels of lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT). After 2 hours of liver reperfusion, C(dyn) was reduced by ∼25%, while RI increased by ∼16% (P < .05). The decreased C(dyn) and increased RI were markedly attenuated by melatonin pretreatment (P < .05). Melatonin pretreatment also protected the liver against I/R injury (P < .05), as seen by reduced LDH, GOT and GPT along with markedly reduced hydroxyl radicals (P < .05). Preischemic treatment with melatonin protected lung function against damage by liver I/R. The improvement in lung function was strongly associated with decreased hydroxyl radicals in the lungs. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Analyzing the Impact of Increasing Mechanical Index and Energy Deposition on Shear Wave Speed Reconstruction in Human Liver.

    PubMed

    Deng, Yufeng; Palmeri, Mark L; Rouze, Ned C; Rosenzweig, Stephen J; Abdelmalek, Manal F; Nightingale, Kathryn R

    2015-07-01

    Shear wave elasticity imaging (SWEI) has found success in liver fibrosis staging. This work evaluates hepatic SWEI measurement success as a function of push pulse energy using two mechanical index (MI) values (1.6 and 2.2) over a range of pulse durations. Shear wave speed (SWS) was measured in the livers of 26 study subjects with known or potential chronic liver diseases. Each measurement consisted of eight SWEI sequences, each with different push energy configurations. The rate of successful SWS estimation was linearly proportional to the push energy. SWEI measurements with higher push energy were successful in patients for whom standard push energy levels failed. The findings also suggest that liver capsule depth could be used prospectively to identify patients who would benefit from elevated output. We conclude that there is clinical benefit to using elevated acoustic output for hepatic SWS measurement in patients with deeper livers. Published by Elsevier Inc.

  4. Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats.

    PubMed

    Díaz-Rúa, Rubén; Keijer, Jaap; Palou, Andreu; van Schothorst, Evert M; Oliver, Paula

    2017-08-01

    Intake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition. Moreover, changes in expression of genes involved in acid-base maintenance and oxidative stress indicate alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. Up-regulation of immune-related genes was also observed. In concordance with changes at gene expression level, we observed increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly increased hepatic mRNA and protein levels of HSP90, a marker of liver injury. Thus, we show for the first time that long-term consumption of an HP diet, resulting in a high acid load, results in a hepatic transcriptome signature reflecting increased TG deposition and increased signs of health risk (increased inflammation, alterations in the acid-base equilibrium and oxidative stress). Persistence of this altered metabolic status could have unhealthy consequences. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Increase in the prevalence of arthritis in adulthood among adults exposed to Chinese famine of 1959 to 1961 during childhood: A cross-sectional survey.

    PubMed

    Xu, Xianglong; Liu, Lingli; Xie, Wenxi; Zhang, Yong; Zeng, Huan; Zhang, Fan; Reis, Cesar; Cao, Xianqing; Zhao, Yong

    2017-03-01

    The developmental origins hypothesis postulates that under-nutrition in the early stage of life is associated with an increased risk of disease in adulthood. This study aimed to examine the association of exposure to the Chinese famine of 1959 to 1961 in early life with the risk of arthritis in adulthood.From July to September 2009, the study adopted multistage stratified random sampling cross-sectional survey to recruit 1224 eligible adults in Chongqing. Famine exposure groups were categorized into 3 groups: (1) childhood exposure, (2) fetal exposure, and (3) nonexposure. Self-reported arthritis of physician diagnosis was obtained. A total of 1224 eligible respondents were interviewed, including 299 individuals exposed during childhood, 455 exposed when fetal, and 470 without exposure.The prevalence of arthritis in adulthood among individuals exposed to famine during childhood was significantly higher than those not exposed (17.39% vs 11.28%, odds ratio [OR] = 1.573 with a 95% confidence interval of [CI] [1.020, 2.424]). Persons exposed to famine during the fetal period did not significantly contribute to a higher rate of arthritis in adulthood than those who were not exposed to famine (13.19% vs 11.28%, OR = 1.072, 95% CI = 0.713, 1.613). In addition, education level, the average monthly income, sleep status, and satisfaction of the present living condition were associated with the risk of arthritis in adulthood.Exposure to the Chinese famine during childhood may be associated with an increased risk of arthritis in adulthood. This study suggests that early life nutrition may have an effect on the risk of arthritis in adulthood.

  6. Developmental origins of nonalcoholic fatty liver disease.

    PubMed

    Brumbaugh, David E; Friedman, Jacob E

    2014-01-01

    Obese pregnant women may transmit their metabolic phenotype to offspring, leading to a cycle of obesity and diabetes over generations. Early childhood obesity predicts nonalcoholic fatty liver disease (NAFLD), the most common chronic human liver disease. The fetus may be vulnerable to steatosis because immature fetal adipose depots are not available to buffer the excess transplacental lipid delivery in maternal obesity. In animal models, in utero high-fat diet exposure results in an increase in the accumulation of liver triglycerides in offspring and increased hepatic oxidative stress and apoptosis, perhaps priming the liver for later development of NAFLD. Innate immune dysfunction and necroinflammatory changes have been observed in postnatal offspring liver of animals born to high-fat-fed dams. Postweaning, livers of offspring exposed to maternal high-fat feeding in utero share pathophysiologic features with human NAFLD, including increased de novo lipogenesis and decreased free fatty acid oxidation. Human studies using magnetic resonance imaging have shown that maternal BMI predicts infant intrahepatocellular lipid storage, as seen in animal models. The generational transfer of NAFLD may occur via epigenetic changes in offspring liver. Transmission of microbiota from mother to infant may impact energy retention and immune function that contribute to a predisposition to NAFLD.

  7. High levels of dietary phytosterols affect lipid metabolism and increase liver and plasma TAG in Atlantic salmon (Salmo salar L.).

    PubMed

    Liland, Nina S; Espe, Marit; Rosenlund, Grethe; Waagbø, Rune; Hjelle, Jan I; Lie, Øyvind; Fontanillas, Ramon; Torstensen, Bente E

    2013-12-14

    Replacing dietary fishmeal (FM) and fish oil (FO) with plant ingredients in Atlantic salmon (Salmo salar L.) diets decreases dietary cholesterol and introduces phytosterols. The aim of the present study was to assess the effect of dietary sterol composition on cholesterol metabolism in Atlantic salmon. For this purpose, two dietary trials were performed, in which Atlantic salmon were fed either 100 % FM and FO (FM-FO) diet or one of the three diets with either high (80 %) or medium (40 %) plant protein (PP) and a high (70 %) or medium (35 %) vegetable oil (VO) blend (trial 1); or 70 % PP with either 100 % FO or 80 % of the FO replaced with olive, rapeseed or soyabean oil (trial 2). Replacing ≥ 70 % of FM with PP and ≥ 70 % of FO with either a VO blend or rapeseed oil increased plasma and liver TAG concentrations. These diets contained high levels of phytosterols and low levels of cholesterol. Fish fed low-cholesterol diets, but with less phytosterols, exhibited an increased expression of genes encoding proteins involved in cholesterol uptake and synthesis. The expression of these genes was, however, partially inhibited in rapeseed oil-fed fish possibly due to the high dietary and tissue phytosterol:cholesterol ratio. Atlantic salmon tissue and plasma cholesterol concentrations were maintained stable independent of the dietary sterol content.

  8. Oxidation Stability of Pig Liver Pâté with Increasing Levels of Natural Antioxidants (Grape and Tea)

    PubMed Central

    Pateiro, Mirian; Lorenzo, José M.; Vázquez, José A.; Franco, Daniel

    2015-01-01

    The present study investigated the effect of the addition of increasing levels of the natural antioxidants tea (TEA) and grape seed extracts (GRA) on the physiochemical and oxidative stability of refrigerated stored pig pâtés. In addition, a synthetic antioxidant and a control batch were used, thus a total of eight batches of liver pâté were prepared: CON, BHT, TEA (TEA50, TEA200 and TEA1000) and GRA (GRA50, GRA200 and GRA1000). Pâté samples were analyzed following 0, 4, 8 and 24 weeks of storage. Color parameters were affected by storage period and level of antioxidant extract. Samples with TEA200 and GRA1000 levels of extracts showed lower total color difference between 0 and 24 weeks. At the end of storage period, the lower TBARs values were obtained in samples with the highest concentration on natural extract. Overall, the evolution of volatile compounds showed an increase in those ones that arise from the lipid oxidation and samples with TEA1000 extract showed the lowest values. PMID:26785340

  9. Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus

    SciTech Connect

    Koo, Hyun-Young; Miyashita, Michio; Simon Cho, B.H.; Nakamura, Manabu T.

    2009-12-11

    Diets high in fructose cause hypertriglyceridemia and insulin resistance in part due to simultaneous induction of gluconeogenic and lipogenic genes in liver. We investigated the mechanism underlying the unique pattern of gene induction by dietary fructose. Male Sprague-Dawley rats (n = 6 per group) were meal-fed (4 h/d) either 63% (w/w) glucose or 63% fructose diet. After two weeks, animals were killed at the end of the last meal. Nuclear SREBP-1 was 2.2 times higher in fructose-fed rats than glucose-fed rats. Nuclear FoxO1 was elevated 1.7 times in fructose group, but did not reach significance (P = 0.08). Unexpectedly, no difference was observed in nuclear ChREBP between two groups. However, ChREBP DNA binding was 3.9x higher in fructose-fed animals without an increase in xylulose-5-phospate, a proposed ChREBP activator. In conclusion, the gene induction by dietary fructose is likely to be mediated in part by simultaneously increased ChREBP activity, SREBP-1 and possibly FoxO1 protein in nucleus.

  10. Paracetamol (acetaminophen) decreases hydrogen sulfide tissue concentration in brain but increases it in the heart, liver and kidney in mice.

    PubMed

    Wiliński, Bogdan; Wiliński, Jerzy; Somogyi, Eugeniusz; Góralska, Marta; Piotrowska, Joanna

    2011-01-01

    The biological action ofN-acetyl-p-aminophenol - paracetamol (acetaminophen) has been demonstrated to involve different mechanisms and is still not clear. Hydrogen sulfide (H2S) has been shown to play an important role in many physiological and pathological processes including nociception. The interaction between acetaminophen and endogenous H2S is unknown. Twenty four female CBA strain mice were administered intraperitoneal injections of N-acetyl-p-aminophenol solution: paracetemol in doses of 30 mg/kg b.w. per day (group D1, n = 8) or 100 mg/kg b.w. per day (group D2, n = 8).. The control group (n = 8) received physiological saline in portions of the same volume--0.2 ml. The measurements of tissue H2S concentration were performed with the Siegel spectrophotometric modified method. In the brain, the H2S tissue level decreased, but more significantly in the lower drug dose group. Conversely, there was a significant rise in the H2S tissue concentration in D1 and D2 groups in heart and kidney with the increase more pronounced in the group with the lower paracetamol dose. In the liver only the higher acetaminophen dose elicited a change in H2S concentration, increasing after administration of acetaminophen at 100 mg/kg. Our study demonstrates that paracetamol induces H2S tissue concentration changes in different mouse organs.

  11. Oxidation Stability of Pig Liver Pâté with Increasing Levels of Natural Antioxidants (Grape and Tea).

    PubMed

    Pateiro, Mirian; Lorenzo, José M; Vázquez, José A; Franco, Daniel

    2015-01-27

    The present study investigated the effect of the addition of increasing levels of the natural antioxidants tea (TEA) and grape seed extracts (GRA) on the physiochemical and oxidative stability of refrigerated stored pig pâtés. In addition, a synthetic antioxidant and a control batch were used, thus a total of eight batches of liver pâté were prepared: CON, BHT, TEA (TEA50, TEA200 and TEA1000) and GRA (GRA50, GRA200 and GRA1000). Pâté samples were analyzed following 0, 4, 8 and 24 weeks of storage. Color parameters were affected by storage period and level of antioxidant extract. Samples with TEA200 and GRA1000 levels of extracts showed lower total color difference between 0 and 24 weeks. At the end of storage period, the lower TBARs values were obtained in samples with the highest concentration on natural extract. Overall, the evolution of volatile compounds showed an increase in those ones that arise from the lipid oxidation and samples with TEA1000 extract showed the lowest values.

  12. Transplantation of a human iPSC-derived hepatocyte sheet increases survival in mice with acute liver failure.

    PubMed

    Nagamoto, Yasuhito; Takayama, Kazuo; Ohashi, Kazuo; Okamoto, Ryota; Sakurai, Fuminori; Tachibana, Masashi; Kawabata, Kenji; Mizuguchi, Hiroyuki

    2016-05-01

    Hepatocyte transplantation is one of the most attractive approaches for the treatment of patients with liver failure. Because human induced pluripotent stem cell-derived hepatocyte-like cells (iPS-HLCs) can be produced on a large scale and generated from a patient with liver failure, they are expected to be used for hepatocyte transplantation. However, when using conventional transplantation methods, i.e., intrasplenic or portal venous infusion, it is difficult to control the engraftment efficiency and avoid unexpected engraftment in other organs because the transplanted cells are delivered into blood circulation before their liver engraftment. In this study, to resolve these issues, we attempted to employ a cell sheet engineering technology for experimental hepatocyte transplantation. The human iPS-HLC sheets were attached onto the liver surfaces of mice with liver injury. This method reduced unexpected engraftment in organs other than the liver compared to that by intrasplenic transplantation. Human albumin levels in the mice with human iPS-HLC sheets were significantly higher than those in the intrasplenically-transplanted mice, suggesting the high potential for cell engraftment of the sheet transplantation procedure. In addition, human iPS-HLC sheet transplantation successfully ameliorated lethal acute liver injury induced by the infusion of carbon tetrachloride (CCl4). Moreover, we found that the hepatocyte growth factor secreted from the human iPS-HLC sheet played an important role in rescuing of mice from acute hepatic failure. Human iPS-HLC sheet transplantation would be a useful and reliable therapeutic approach for a patient with severe liver diseases. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  13. Introduction of complementary feeding before 4months of age increases the risk of childhood overweight or obesity: a meta-analysis of prospective cohort studies.

    PubMed

    Wang, Jing; Wu, Yuanjue; Xiong, Guoping; Chao, Tingting; Jin, Qiu; Liu, Rui; Hao, Liping; Wei, Sheng; Yang, Nianhong; Yang, Xuefeng

    2016-08-01

    The association between the age at introduction of complementary feeding and the risk of overweight or obesity during childhood has been hotly debated, but the result remains uncertain. This meta-analysis of prospective cohort studies attempted to evaluate this association, as well as provide evidence for infant feeding recommendations. The PubMed, Embase, and Cochrane databases were systematically searched for relevant original articles published prior to March 1, 2015 that met predefined inclusion criteria. The pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated using fix-effect or random-effect models, which were chosen based on heterogeneity among studies. Ten articles consisting of 13 studies, where 8 measured being overweight as an outcome and 5 measured being obese, were included in this meta-analysis. There were a total of 63,605 participants and 11,900 incident cases in the overweight studies, and 56,136 individuals and 3246 incident cases in the obese studies. The pooled results revealed that introducing complementary foods before 4months of age compared to at 4 to 6months was associated with an increased risk of being overweight (RR, 1.18; 95% CI, 1.06-1.31) or obese (RR, 1.33; 95% CI, 1.07-1.64) during childhood. No significant relationship was observed between delaying introduction of complementary foods after 6months of age, and being overweight (RR, 1.01; 95% CI, 0.90-1.13) or obese (RR, 1.02; 95% CI, 0.91-1.14) during childhood. The results of this study suggest that the introduction of complementary foods to infants before 4months of age should be avoided to protect against childhood obesity.

  14. Maltreatment in childhood substantially increases the risk of adult depression and anxiety in prospective cohort studies: systematic review, meta-analysis, and proportional attributable fractions.

    PubMed

    Li, M; D'Arcy, C; Meng, X

    2016-03-01

    Literature supports a strong relationship between childhood maltreatment and mental illness but most studies reviewed are cross-sectional and/or use recall to assess maltreatment and are thus prone to temporality and recall bias. Research on the potential prospective impact of maltreatment reduction on the incidence of psychiatric disorders is scarce. Electronic databases and grey literature from 1990 to 2014 were searched for English-language cohort studies with criteria for depression and/or anxiety and non-recall measurement of childhood maltreatment. Systematic review with meta-analysis synthesized the results. Study quality, heterogeneity, and publication bias were examined. Initial screening of titles and abstracts resulted in 199 papers being reviewed. Eight high-quality articles met eligibility criteria. Population attributable fractions (PAFs) estimated potential preventive impact. The pooled odds ratio (OR) between any type of maltreatment and depression was 2.03 [95% confidence interval (CI) 1.37-3.01] and 2.70 (95% CI 2.10-3.47) for anxiety. For specific types of maltreatment and depression or anxiety disorders, the ORs were: physical abuse (OR 2.00, 95% CI 1.25-3.19), sexual abuse (OR 2.66, 95% CI 1.88-3.75), and neglect (OR 1.74, 95% CI 1.35-2.23). PAFs suggest that over one-half of global depression and anxiety cases are potentially attributable to self-reported childhood maltreatment. A 10-25% reduction in maltreatment could potentially prevent 31.4-80.3 million depression and anxiety cases worldwide. This review provides robust evidence of childhood maltreatment increasing the risk for depression and anxiety, and reinforces the need for effective programs and policies to reduce its occurrence.

  15. Increased Childhood Abuse in Patients With Premenstrual Dysphoric Disorder in a Turkish Sample: A Cross-Sectional Study

    PubMed Central

    Albayrak, Yakup; Sahin, Basak

    2014-01-01

    Objective: Abuse is considered to have a place in the etiology of various psychiatric disorders. Premenstrual dysphoric disorder (PMDD) is one of the psychiatric disorders for which abuse could be an etiologic factor; however, few studies have investigated the relationship between abuse and PMDD. In this study, our aim was to investigate childhood abuse in patients with PMDD and compare them with healthy female subjects. Method: This cross-sectional study included 70 women with PMDD (DSM-IV-TR criteria) who were admitted to the outpatient psychiatry clinic of Ankara Yenimahalle State Hospital, Ankara, Turkey, between December 2012 and December 2013. Additionally, 78 healthy controls were included in the study. Sociodemographic, familial, and reproductive period characteristics of the women were recorded. All subjects were administered the Premenstrual Syndrome Scale (PMSS) and the Childhood Trauma Questionnaire (CTQ). Results: Among the sociodemographic characteristics, being a university graduate (76.9%) and being a public servant (70.5%) were significantly higher in the healthy control group (P = .01 and P = .01, respectively). A family history of PMDD (31.4%), a history of postpartum psychiatric disorders (11.4%), and a history of attempted suicide (7.1%) were higher in the PMDD group compared with the healthy control group (P = .001, P = .003, and P = .024, respectively). Significant differences were also found between PMDD and healthy controls in PMSS score (P ≤ .001), CTQ total scores (P = .002), and subscale scores including emotional abuse and emotional neglect (P = .004), physical abuse (P = .009), and sexual abuse (P = .012). Conclusions: To our knowledge, the present study is the first to investigate associations between PMDD and childhood abuse from Turkey. More comprehensive studies on this topic with larger sample sizes are required to enrich the literature and enable practitioners to be more effective in clinical practice. PMID:25664213

  16. Stages of Childhood Liver Cancer

    MedlinePlus

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  17. Adipocyte (Pro)Renin-Receptor Deficiency Induces Lipodystrophy, Liver Steatosis and Increases Blood Pressure in Male Mice.

    PubMed

    Wu, Chia-Hua; Mohammadmoradi, Shayan; Thompson, Joel; Su, Wen; Gong, Ming; Nguyen, Genevieve; Yiannikouris, Frédérique

    2016-07-01

    Adipose tissue dysfunction related to obesity is overwhelmingly associated with increased risk of developing cardiovascular diseases. In the setting of obesity, (pro)renin receptor (PRR) is increased in adipose tissue of mice. We sought to determine the physiological consequences of adipocyte-PRR deficiency using adiponectin-Cre mice. We report a unique model of adipocyte-PRR-deficient mice (PRR(Adi/Y)) with almost no detectable white adipose tissues. As a consequence, the livers of PRR(Adi/Y) mice were enlarged and demonstrated a marked accumulation of lipids. Adipocyte-specific deficiency of PRR increased systolic blood pressure and the concentration of soluble PRR in plasma. To determine whether adipocyte-PRR was involved in the development of obesity-induced hypertension, mice were fed a low-fat or a high-fat diet for 16 weeks. Adipocyte-PRR-deficient mice were resistant to diet-induced obesity. Both high-fat- and low-fat-fed PRR(Adi/Y) mice had elevated insulin levels. Interestingly, adipocyte-PRR deficiency improved glucose tolerance in high-fat-fed PRR(Adi/Y) mice. In response to feeding either low-fat or high-fat diets, systolic blood pressure was greater in PRR(Adi/Y) mice than in control mice. High-fat feeding elevated soluble PRR concentration in control and PRR(Adi/Y) mice. In vitro knockdown of PRR by siRNA significantly decreased mRNA abundance of PPARγ (peroxisome proliferator-activated receptor gamma), suggesting an important role for PRR in adipogenesis. Our data indicate that adipocyte-PRR is involved in lipid homeostasis and glucose and insulin homeostasis, and that soluble PRR may be a predictor of metabolic disturbances and play a role in systolic blood pressure regulation.

  18. The relationship between pediatric nonalcoholic fatty liver disease and cardiovascular risk factors and increased risk of atherosclerosis in obese children.

    PubMed

    Gökçe, Selim; Atbinici, Zehra; Aycan, Zehra; Cınar, Hasibe Gökçe; Zorlu, Pelin

    2013-02-01

    To investigate the relationship between nonalcoholic fatty liver disease and cardiovascular risk factors and increased risk of atherosclerosis in obese children. The study included 80 consecutive obese children who were stratified into group 1 [ultrasonographically diagnosed with NAFLD (n = 50)] and group 2 [not diagnosed with NAFLD (n = 30)]. The control group included 30 healthy children. The groups were compared in terms of clinical cardiovascular risk factors and carotid intimal medial thickness (CIMT) (as a marker of atherosclerosis) measured using B-mode ultrasound. Mean body mass index (BMI) and blood pressure (BP), as well as the frequency of dyslipidemia, metabolic syndrome (MetS), and insulin resistance (IR), were similar in groups 1 and 2. Mean BMI and triglyceride (TG) levels, and the frequency of IR and MetS, increased significantly as the grade of steatosis increased. Mean CIMT in group 1 was significantly greater than that in the control group (P < 0.01). There was a positive correlation between CIMT and age, BP, and BMI in groups 1 and 2. In addition, CIMT was correlated with TG, low high-density lipoprotein (HDL) cholesterol, MetS, and IR only in group 1. Linear regression analysis between CIMT and age, BP, BMI, TG level, HDL cholesterol level, IR, MetS, and grade of steatosis yielded a significant difference only for grade of steatosis. Cardiovascular risk factors are more impressive and CIMT was significantly higher in group 1 than in group 2 and the control group, indicating that they are associated with greater risk of atherosclerosis and future adverse cardiovascular events.

  19. Copper-binding proteins in liver of bluegills exposed to increased soluble copper under field and laboratory conditions.

    PubMed Central

    Harrison, F L; Lam, J R

    1986-01-01

    Livers from bluegills exposed to increased soluble copper (Cu) under field and laboratory conditions were analyzed to determine the concentration and distribution of Cu in metalloproteins of different molecular size. Analyses were performed on bluegills collected from the impoundment of the H. B. Robinson Steam Electric Plant (Florence, SC) near the effluent discharge from the power plant, near the water intake to the cooling system, and from a control pond as well as on bluegills exposed under controlled laboratory conditions. Metalloproteins were separated into low molecular weight (LMW), intermediate molecular weight (IMW), and high molecular weight (HMW) fractions by using high-performance liquid chromatography. In the field-exposed bluegills, Cu concentrations in the LMW, IMW, and HMW fractions were highest in bluegills from the discharge site and lowest in those from the control pond. In the laboratory-exposed bluegills, Cu concentrations in the fractions increased with exposure concentration and time. Concentrations of Cu in the LMW protein fraction and pellet of bluegills exposed to 160 micrograms Cu/L appeared to plateau with long exposure times, whereas those in the HMW fraction continued to increase. Bluegills maintained in 80 micrograms Cu/L water at pH 5.5 accumulated lower concentrations of Cu in the LMW and pellet fractions and higher amounts in the HMW than in those maintained in 80 micrograms Cu/L at pH 7.0. Mortality was dependent on exposure concentration and duration and was higher in bluegills maintained in water at pH 5.5 than at pH 7.0. PMID:3709431

  20. Short-term ingestion of a high protein diet increases liver and kidney mass and protein accretion but not cellularity in young pigs.

    PubMed

    Schoknecht, P A; Pond, W G

    1993-06-01

    Increased visceral organ mass raises the energy cost of maintenance in animals. To determine the nutritional factors that affect organ size during growth and development, we studied 12 genetically obese 4-week-old pigs for 14 days. The piglets had free access to either a control (17% protein) or a high protein (34%) diet. They were sacrificed after 14 days and their empty gastrointestinal tracts, livers, and kidneys were weighed and samples were analyzed for protein and DNA concentrations. The absolute and relative (percentage of body weight) weights of liver and kidneys were greater in high protein than control piglets: liver (313 vs 246 g, SD = 24, P < 0.09; 3.61% vs 3.18%, SD = 0.04, P < 0.01); kidneys (57 vs 41 g, SD = 4, P < 0.04; 0.66% vs 0.55%, SD = 0.02, P < 0.01). Protein content was greater in high protein than control pigs in both liver (48.2 vs 34.0 g, SD = 3.4, P < 0.03) and kidneys (6.0 vs 4.6 g, SD = 0.5, P < 0.06). Liver and kidney total DNA were unaffected by diet in both groups. The protein to DNA ratio was greater in high protein than control pigs in both liver (45.4 vs 39.0, SD = 0.6, P < 0.01) and kidneys (26.6 vs 24.9, SD = 0.4, P < 0.02). We conclude that when weaned pigs have free access to a high protein diet (2 x requirement) for 2 weeks, liver and kidney protein accretion increases, suggesting cell hypertrophy, with no clear evidence of cell hyperplasia.

  1. Ablation of interaction between IL-33 and ST2+ regulatory T cells increases immune cell-mediated hepatitis and activated NK cell liver infiltration.

    PubMed

    Noel, Gregory; Arshad, Muhammad Imran; Filliol, Aveline; Genet, Valentine; Rauch, Michel; Lucas-Clerc, Catherine; Lehuen, Agnès; Girard, Jean-Philippe; Piquet-Pellorce, Claire; Samson, Michel

    2016-08-01

    The IL-33/ST2 axis plays a protective role in T-cell-mediated hepatitis, but little is known about the functional impact of endogenous IL-33 on liver immunopathology. We used IL-33-deficient mice to investigate the functional effect of endogenous IL-33 in concanavalin A (Con A)-hepatitis. IL-33(-/-) mice displayed more severe Con A liver injury than wild-type (WT) mice, consistent with a hepatoprotective effect of IL-33. The more severe hepatic injury in IL-33(-/-) mice was associated with significantly higher levels of TNF-α and IL-1β and a larger number of NK cells infiltrating the liver. The expression of Th2 cytokines (IL-4, IL-10) and IL-17 was not significantly varied between WT and IL-33(-/-) mice following Con A-hepatitis. The percentage of CD25(+) NK cells was significantly higher in the livers of IL-33(-/-) mice than in WT mice in association with upregulated expression of CXCR3 in the liver. Regulatory T cells (Treg cells) strongly infiltrated the liver in both WT and IL-33(-/-) mice, but Con A treatment increased their membrane expression of ST2 and CD25 only in WT mice. In vitro, IL-33 had a significant survival effect, increasing the total number of splenocytes, including B cells, CD4(+) and CD8(+) T cells, and the frequency of ST2(+) Treg cells. In conclusion, IL-33 acts as a potent immune modulator protecting the liver through activation of ST2(+) Treg cells and control of NK cells. Copyright © 2016 the American Physiological Society.

  2. Serum fetuin B level increased in subjects of nonalcoholic fatty liver disease: a case-control study.

    PubMed

    Zhu, Jinzhou; Wan, Xingyong; Wang, Yuming; Zhu, Kefu; Li, Chunxiao; Yu, Chaohui; Li, Youming

    2017-04-01

    Fetuin is an endogenous inhibitor of the insulin receptor tyrosine kinase. Recent studies supported the possible role of fetuin B in metabolic diseases. This study is to evaluate the role of serum fetuin B in nonalcoholic fatty liver disease (NAFLD). A hospital-based case-control study of 184 subjects was conducted. Serum level of fetuin B was measured by enzyme-linked immunosorbent assay. The serum level of fetuin B in the control (91.0 ± 36.9 μg/ml) was lower than it in NAFLD (108.7 ± 38.5 μg/ml, P < 0.001). The percentage of NAFLD increased (42.9%, 58.7% and 60.2%; P < 0.001; linear-by-linear association: P < 0.001), as fetuin B concentration elevated in its tertiles, after adjustment of body mass index (BMI). Furthermore, compared with the 1st tertile, the 3rd tertile of fetuin B indicated an association with the presence of NAFLD (adjusted odds ratio = 2.087, 95% confidence interval [1.016 - 3.937], P = 0.023), after controlling age, sex, BMI, diabetes, hypertension and hypertriglyceridemia. Lastly, fetuin B correlated with diastolic blood pressure, serum alanine transaminase and triglycerides, among the controls. It suggested a potential association between serum fetuin B and the presence of NAFLD.

  3. Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis

    PubMed Central

    Carrière, Virginie; Arshad, Muhammad Imran; Le Seyec, Jacques; Lefevre, Benjamin; Farooq, Muhammad; Jan, Aurélien; Manuel, Christelle; Touami-Bernard, Laurence; Lucas-Clerc, Catherine; Genet, Valentine; Gascan, Hugues; Girard, Jean-Philippe; Chalmel, Frédéric; Lamontagne, Lucie; Piquet-Pellorce, Claire

    2017-01-01

    The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver. PMID:28607531

  4. N-Aralkyl substitution increases the affinity of adrenergic drugs for the alpha-adrenoceptor in rat liver.

    PubMed Central

    Aggerbeck, M; Guellaën, G; Hanoune, J

    1979-01-01

    1 The alpha-adrenoceptor of rat liver plasma membranes was studied by use of the specific alpha-antagonist [3H]-dihydroergocryptine ([3H]-DHEC). Catecholamines and adrenergic compounds displayed an order of affinity that is typical of an alpha-receptor. Nevertheless, protokylol, a potent beta-adrenoceptor agonist, exhibited a higher affinity than that of adrenaline for alpha-sites. This result might be due to its bulky substituent on the amino group. 2 Further displacement experiments between [3H]-DHEC and four pairs of drugs differently substituted on the amino group (isoprenaline vs Cc-25, orciprenaline vs fenoterol, AH 3474 vs labetalol, pindolol vs hydroxybenzylpindolol) provided evidence that N-alkyl substitution decreased the affinity for alpha-sites (20 micromolar less than KD less than 200 micromolar), whereas an N-aralkyl one