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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. General Information about Childhood Liver Cancer

    MedlinePlus

    ... Childhood Liver Cancer Treatment (PDQ®)–Patient Version General Information About Childhood Liver Cancer Go to Health Professional ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  3. Viral infections of the liver in childhood

    PubMed Central

    Zuckerman, A. J.

    1974-01-01

    Hepatitis A and hepatitis B viruses and yellow fever virus are the most important causes of acute inflammation of the liver. Hepatitis is also frequently associated with other common viral infections such as cytomegalovirus (human herpesvirus 5) and EB virus (human herpesvirus 4). In addition, there are a number of viruses which occasionally display increased hepatotropism producing a clinical picture which is similar to classical hepatitis. PMID:4377172

  4. Addressing childhood obesity through increased physical activity.

    PubMed

    Hills, Andrew P; Okely, Anthony D; Baur, Louise A

    2010-10-01

    Obesity is affecting an increasing proportion of children globally. Despite an appreciation that physical activity is essential for the normal growth and development of children and prevents obesity and obesity-related health problems, too few children are physically active. A concurrent problem is that today's young people spend more time than previous generations did in sedentary pursuits, including watching television and engaging in screen-based games. Active behavior has been displaced by these inactive recreational choices, which has contributed to reductions in activity-related energy expenditure. Implementation of multifactorial solutions considered to offer the best chance of combating these trends is urgently required to redress the energy imbalance that characterizes obesity. The counterproductive 'shame and blame' mentality that apportions responsibility for the childhood obesity problem to sufferers, their parents, teachers or health-care providers needs to be changed. Instead, these groups should offer constant support and encouragement to promote appropriate physical activity in children. Failure to provide activity opportunities will increase the likelihood that the children of today will live less healthy (and possibly shorter) lives than their parents. PMID:20736922

  5. Increased plasma homocysteine in liver cirrhosis.

    PubMed

    Bosy-Westphal, A; Petersen, S; Hinrichsen, H; Czech, N; J Müller, M

    2001-05-01

    Background: Homocysteine (Hcy), is an atherogenic and thrombogenic risk factor which has also been proposed to be involved in hepatic fibrinogenesis. Hcy metabolism, depends on the cofactors folate, vit. B12, and the vit. B6 vitamer pyridoxalphosphate (PLP). Metabolism of these vitamins is frequently disturbed in cirrhotics, but little is known about plasma Hcy levels in these patients. Methods: Plasma levels of Hcy, methionine, serine, cysteine, PLP, vit. B12 and folate, and standard clinical/biochemical parameters of liver disease were measured in 43 postabsorptive patients with biopsy proven cirrhosis of different origin. Results: 74% of the patients had elevated plasma Hcy levels defined as >13.4 µmol/l (mean+2SD of healthy age matched controls). Increased plasma Hcy concentrations were seen in alcoholic as well as in non-alcoholic cirrhosis. Excluding patients with impaired renal function (n=7), Hcy concentrations remained elevated in 69% of the patients. We found a high prevalence of pathological plasma vitamin concentrations of 33% for increased vit. B12 levels and 5% and 80% for decreased folate and vit. B6 levels, respectively. Mean plasma vitamin B12 concentrations increased, folate remained unchanged and PLP concentrations decreased with deteriorating liver function. Hcy concentrations were correlated with levels of creatinine (r=0.44, P<0.01), serine (r=-0.46, P<0.01), and cysteine (r=0.38, P<0.05), but showed no association with parameters of liver function and with plasma levels of folate, vit. B12 und vit. B6. This was contrary to data obtained in healthy individuals. In a stepwise multiple regression serine and cysteine best explained the variance in Hcy levels. Conclusions: Elevated basal Hcy-plasma levels are frequently seen cirrhotic patients. Variations of Hcy concentration in liver cirrhosis are not explained by plasma levels of cofactors of Hcy metabolism. PMID:11282484

  6. The Childhood Incidents That Increase Later Suicide Risk

    MedlinePlus

    ... Incidents That Increase Later Suicide Risk Exposure to domestic violence, abuse cast a long shadow, study finds To ... 13, 2016 (HealthDay News) -- Adults who witnessed parental domestic violence in childhood are at increased risk for suicide ...

  7. Undifferentiated embryonal liver sarcoma in childhood: A case report

    PubMed Central

    HE, BIN; XU, KEYU; HUANG, KATE; HUANG, YUEHAN; LI, PENG; CHEN, ZHENKUN; SHI, HONGQI; ZHANG, QIYU; SHAN, YUNFENG

    2014-01-01

    In order to improve the diagnosis and therapy of undifferentiated embryonal liver sarcoma (UELS), the present study presents the case of a 9-year-old female with UELS and discusses UELS in childhood. The patient presented with abdominal pain and fever. The laboratory tests, radiographic examination and pathological features presented by the female were similar to those of typical cases of UELS reported in childhood. The patient initially received surgical treatment and the immunohistochemical findings suggested that the patient had UELS. The patient’s parents refused adjuvant chemotherapy and demonstrated a right prerenal mass 6 months post-surgery. Microscopic examination revealed that the tumor was evidence of undifferentiated embryonal sarcoma recurrence. However, the patient was comfortable and physical examination revealed no abnormal conditions. In addition, the laboratory results were normal. Abdominal computed tomography scan and ultrasound were performed every 3 months to monitor the tumor recurrence. At the time of writing, it has been 6 months after the second surgical procedure and there has been no appearence of abnormalities. Previous studies have shown that patients who receive combined therapy with complete tumor resection and adjuvant chemotherapy have a longer survival time than those who undergo surgical therapy alone. Complete tumor resection combined with adjuvant chemotherapy may reduce the risk of recurrence and enhance the survival time in patients with UELS. PMID:25120671

  8. Undifferentiated embryonal liver sarcoma in childhood: A case report.

    PubMed

    He, Bin; Xu, Keyu; Huang, Kate; Huang, Yuehan; Li, Peng; Chen, Zhenkun; Shi, Hongqi; Zhang, Qiyu; Shan, Yunfeng

    2014-09-01

    In order to improve the diagnosis and therapy of undifferentiated embryonal liver sarcoma (UELS), the present study presents the case of a 9-year-old female with UELS and discusses UELS in childhood. The patient presented with abdominal pain and fever. The laboratory tests, radiographic examination and pathological features presented by the female were similar to those of typical cases of UELS reported in childhood. The patient initially received surgical treatment and the immunohistochemical findings suggested that the patient had UELS. The patient's parents refused adjuvant chemotherapy and demonstrated a right prerenal mass 6 months post-surgery. Microscopic examination revealed that the tumor was evidence of undifferentiated embryonal sarcoma recurrence. However, the patient was comfortable and physical examination revealed no abnormal conditions. In addition, the laboratory results were normal. Abdominal computed tomography scan and ultrasound were performed every 3 months to monitor the tumor recurrence. At the time of writing, it has been 6 months after the second surgical procedure and there has been no appearence of abnormalities. Previous studies have shown that patients who receive combined therapy with complete tumor resection and adjuvant chemotherapy have a longer survival time than those who undergo surgical therapy alone. Complete tumor resection combined with adjuvant chemotherapy may reduce the risk of recurrence and enhance the survival time in patients with UELS. PMID:25120671

  9. Early childhood sexual abuse increases suicidal intent.

    PubMed

    Lopez-Castroman, Jorge; Melhem, Nadine; Birmaher, Boris; Greenhill, Laurence; Kolko, David; Stanley, Barbara; Zelazny, Jamie; Brodsky, Beth; Garcia-Nieto, Rebeca; Burke, Ainsley K; Mann, J John; Brent, David A; Oquendo, Maria A

    2013-06-01

    Childhood sexual abuse has been consistently associated with suicidal behavior. We studied suicide attempt features in depressed individuals sexually abused as children. On average, sexual abuse started before age 9. It frequently coexisted with physical abuse. Suicide attempters more often had personality disorders and had endured abuse for longer, but did not differ in terms of other clinical characteristics from non-attempters. Earlier onset of sexual abuse and its duration were associated with more suicide attempts. However, when personality disorders were included in the regression model, only these disorders predicted number of attempts. The severity of sexual abuse and the coexistence of physical abuse were correlated with age at first suicide attempt. However, only severity of sexual abuse was marginally associated with age at first suicide attempt in the regression model. Finally, the earlier the age of onset of sexual abuse, the higher the intent, even after controlling for age, sex and personality disorders. This suggests that the characteristics of childhood sexual abuse, especially age of onset, should be considered when studying the risk for suicidal behavior in abused populations. PMID:23737424

  10. Early childhood sexual abuse increases suicidal intent

    PubMed Central

    Lopez-Castroman, Jorge; Melhem, Nadine; Birmaher, Boris; Greenhill, Laurence; Kolko, David; Stanley, Barbara; Zelazny, Jamie; Brodsky, Beth; Garcia-Nieto, Rebeca; Burke, Ainsley K; Mann, J John; Brent, David A; Oquendo, Maria A

    2013-01-01

    Childhood sexual abuse has been consistently associated with suicidal behavior. We studied suicide attempt features in depressed individuals sexually abused as children. On average, sexual abuse started before age 9. It frequently coexisted with physical abuse. Suicide attempters more often had personality disorders and had endured abuse for longer, but did not differ in terms of other clinical characteristics from non-attempters. Earlier onset of sexual abuse and its duration were associated with more suicide attempts. However, when personality disorders were included in the regression model, only these disorders predicted number of attempts. The severity of sexual abuse and the coexistence of physical abuse were correlated with age at first suicide attempt. However, only severity of sexual abuse was marginally associated with age at first suicide attempt in the regression model. Finally, the earlier the age of onset of sexual abuse, the higher the intent, even after controlling for age, sex and personality disorders. This suggests that the characteristics of childhood sexual abuse, especially age of onset, should be considered when studying the risk for suicidal behavior in abused populations. PMID:23737424

  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. PMID:26757994

  12. 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.

  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 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.

  14. 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

  15. 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

  16. 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

    2016-01-01

    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

  17. Increased Porphyrins in Primary Liver Cancer Mainly Reflect a Parallel Liver Disease

    PubMed Central

    Kaczynski, Jerzy; Hansson, Göran; Wallerstedt, Sven

    2009-01-01

    Hepatic porphyries have been associated with an increased risk of primary liver cancer (PLC), which on the other hand may cause an increased porphyrin production. To evaluate the role of an underlying liver disorder we analyzed porphyrins in patients with hepatocellular carcinoma (HCC) (n = 65), cholangiocellular carcinoma (n = 3), or suspected PLC, which turned out to be metastases (n = 18) or a benign disorder (n = 11). None of the patients had a family history of porphyry or clinical signs of porphyry. Increased aminolevulinic acid or porphyrin values were common not only in patients with PLC (43%) but also in metastatic (50%) and benign (64%) liver disorders. The corresponding proportion for HCC patients with liver cirrhosis (55%) was higher (P < .05) than in those without cirrhosis (17%). We conclude that symptomatic porphyries are unusual in PLC, whereas elevated urinary and/or faecal porphyrins are common, primarily reflecting a parallel liver disease and not the PLC. PMID:19841684

  18. Significance of increased `splenic uptake' on liver scintiscanning

    PubMed Central

    Eddleston, A. L. W. F.; Blendis, L. M.; Osborn, S. B.; Williams, Roger

    1969-01-01

    Peak activity over the spleen as a percentage of peak activity over the liver was measured in 265 99mTechnetium sulphur colloid liver scintiscans. The value exceeded 70% in 50 cases. In 32 of these cirrhosis was present; the other 18 scans were from patients with a wide variety of conditions, including secondary deposits, hepatitis, and diseases involving the reticuloendothelial system. A measure of the total activity in the spleen was derived from the peak activity and the length of the spleen. In cirrhosis this was closely related to the finding of oesophageal varices thus showing the importance of a collateral circulation (which allows colloid to bypass the liver) in the increased uptake of colloid by the spleen. In eight patients with hepatosplenomegaly due to blood dyscrasia or disease involving the reticuloendothelial system, total activities in the liver and spleen were estimated from the anteroposterior colour dot scan, and both liver and spleen blood flow were measured by methods independent of reticuloendothelial cell function. The results showed that the main factor causing increased uptake of colloid by the spleen in these diseases was an increased blood flow in the spleen relative to that in the liver. ImagesFIG. 1FIG. 5 PMID:5386628

  19. 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

    2016-01-01

    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

  20. 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

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

    PubMed

    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, we 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 (P less than 0.05) or fasted (P less than 0.05) state and after an oral glucose tolerance test (n = 8) (P less than 0.05). 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. From control animals, killed at the same time of day, muscles and liver were also obtained. Insulin binding to plasma membranes increased in S, P, and EDL (P less than 0.05) but not in WG (P = 0.07), RG (P greater than 0.1), or in liver (P greater than 0.1). There were insulin binding differences among muscles (P less than 0.05). 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. PMID:3526921

  2. Appendectomy correlates with increased risk of pyogenic liver abscess

    PubMed Central

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

    2016-01-01

    Abstract Little is known on the association between appendectomy and pyogenic liver abscess. The objective of this study was to investigate the association between appendectomy and the risk of pyogenic liver abscess in Taiwan. This population-based retrospective cohort study was conducted using the hospitalization dataset of the Taiwan National Health Insurance Program. There were 212,530 subjects age 20 to 84 years with newly diagnosed appendectomy as the appendectomy group since 1998 to 2010, and 850,099 randomly selected subjects without appendectomy as the nonappendectomy group. Both appendectomy and nonappendectomy groups were matched with sex, age, comorbidities, and index year of diagnosing appendectomy. The incidence of pyogenic liver abscess at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was applied to investigate the hazard ratio (HR) and 95% confidence interval (CI) for risk of pyogenic liver abscess associated with appendectomy and other comorbidities including alcoholism, biliary stone, chronic kidney disease, chronic liver diseases, and diabetes mellitus. The overall incidence of pyogenic liver abscess was 1.73-fold greater in the appendectomy group than that in the nonappendectomy group (3.85 vs 2.22 per 10,000 person-years, 95% CI 1.71, 1.76). The multivariable regression analysis disclosed that the adjusted HR of pyogenic liver abscess was 1.77 for the appendectomy group (95% CI 1.59, 1.97), when compared with the nonappendectomy group. Appendectomy is associated with increased hazard of pyogenic liver abscess. Further studies remain necessary to confirm our findings. PMID:27368018

  3. 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,…

  4. Increased metallothionein in mouse liver, kidneys, and duodenum during lactation.

    PubMed

    Solaiman, D; Jonah, M M; Miyazaki, W; Ho, G; Bhattacharyya, M H

    2001-03-01

    Lactation-induced increases in cadmium absorption and retention have been demonstrated in mid-lactating mice, but no systematic measurements of endogenous metal-binding protein concentrations during lactation have been reported. Using Cd/hemoglobin radioassay, this study detected significant increases in metallothionein (MT) concentrations in liver (4-fold), kidneys (2-fold), and duodenum (2-fold), but not jejunum, of mouse dams on days 13 and 20 of lactation. These increases occurred in the absence of cadmium exposure and were specific to the lactation period; dams 5 days after weaning showed MT levels that were similar to those of nonpregnant (NP) mice. Similarly, Northern blot analyses of livers from lactating mice demonstrated that MT mRNA concentrations in maternal liver during mid-lactation were 6-fold higher than those observed 5 days after pups were weaned. Gel filtration of final supernatants from the Cd/hemoglobin assay confirmed that the Cd-binding molecule induced during lactation was indeed metallothionein. In addition, chromatographic analyses of cytosols from tissues taken from dams administered small amounts of Cd (66 ng/mouse) showed that the trace amounts of Cd absorbed through the maternal gastrointestinal tract during mid-lactation were also bound to the MT. These results indicate MT induction in mouse dams occurs as a physiological consequence of lactation, requiring no external stimulus. This induced MT participates in binding low levels of dietary cadmium consumed by the dam. During lactation, elevated maternal MT may affect pathways for essential trace metals as well as sequester toxic metals harmful to the neonate. Multiparous humans may have increased risk of accumulating environmental Cd. PMID:11222885

  5. 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…

  6. 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

  7. 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. PMID:27194488

  8. 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

  9. 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

  10. Evaluation of hypointense liver lesions during hepatobiliary phase MR imaging in normal and cirrhotic livers: is increasing flip angle reliable?

    PubMed

    Xiao, Yu-dong; Ma, Cong; Liu, Jun; Li, Hua-bing; Zhang, Zi-shu; Zhou, Shun-ke

    2016-01-01

    Gd-EOB-DTPA is a newly developed liver specific magnetic resonance contrast agent, which is widely used for focal liver lesion (FLL) detection and liver function evaluation. However, it has been demonstrated that hepatocytes uptake of Gd-EOB-DTPA obviously decreased in cirrhotic liver, and cirrhotic liver parenchyma may show reduced enhancement in hepatobiliary phase, which would result in decreased liver-to-lesion contrast (LLC) and liver to lesion signal intensity ratio (LLSIR). Therefore, it is important to improve the image quality in cirrhotic liver, as it may alter therapeutic strategy. In this paper, we have shown adjustments of the flip angle (FA) provides a simple step to achieve better image quality for evaluation of FLLs, especially to those patients with severe liver cirrhosis. On the basis of our quantitative analysis, both of the LLC and the LLSIR with high FA protocol were always higher than those of low FA protocol. Additionally, on high FA images, more FLLs were detected, peritumoral invasion was found, boundary of the tumor was more remarkably, and better visualization of bile duct was observed. In conclusion, for the patient with severe liver cirrhosis, increasing FA can obviously improve the image quality, which is helpful for FLLs depiction. PMID:26732462

  11. 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

  12. Percutaneous Portal Vein Embolization Increases the Feasibility and Safety of Major Liver Resection for Hepatocellular Carcinoma in Injured Liver

    PubMed Central

    Azoulay, Daniel; Castaing, Denis; Krissat, Jinane; Smail, Alloua; Marin Hargreaves, Guillermo; Lemoine, Antoinette; Emile, Jean-François; Bismuth, Henri

    2000-01-01

    Objective To assess the influence of preoperative portal vein embolization (PVE) on the long-term outcome of liver resection for hepatocellular carcinoma (HCC) in injured liver. Summary Background Data On an healthy liver, PVE of the liver to be resected induces hypertrophy of the remnant liver and increases the safety of hepatectomy. On injured liver, this effect is still debated. Methods During the study period, 10 patients underwent preoperative PVE and 19 patients did not before resection of three or more liver segments for HCC in injured liver (cirrhosis or fibrosis). PVE was performed when the estimated rate of remnant functional liver parenchyma (ERRFLP) assessed by computed tomographic scan volumetry was less than 40%. Results In all patients, PVE was feasible. There were no deaths or complications. The ERRFLP after PVE was significantly increased compared with the pre-PVE value. Liver resection was performed after PVE in 9 of 10 patients, with surgical death and complication rates of 0% and 45%, respectively. PVE increased the number of resections of three or more segments by 47% (9/19). Overall actuarial survival rates with or without previous PVE (89%, 67%, and 44% vs. 80%, 53%, and 53% at 1, 3 and 5 years, respectively) and disease-free actuarial survival rates (86%, 64%, and 21% vs. 55%, 17%, and 17% at 1, 3, and 5 years respectively) after hepatectomy were comparable. Conclusion With the use of PVE, more patients with previously unresectable HCC in injured liver can benefit from resection. Long-term survival rates are comparable to those after resection without PVE. PMID:11066138

  13. 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. PMID:24228657

  14. 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

  15. Childhood Adversity Accelerates Intended Reproductive Timing in Adolescent Girls without Increasing Interest in Infants

    PubMed Central

    Clutterbuck, Stephanie; Adams, Jean; Nettle, Daniel

    2014-01-01

    Women experiencing greater childhood adversity exhibit faster reproductive trajectories. One possible psychological mechanism underlying this phenomenon is an increased interest in infants. Interest in infants is thought to be an adaptation important for successful rearing as it motivates the acquisition of caretaking skills. We investigated the relationships between childhood adversity, intended reproductive timing and interest in infants in a sample of English adolescent girls. Specifically we sought to investigate the relationship between 1) childhood adversity and intended reproductive timing; 2) childhood adversity and interest in infants; and 3) intended reproductive timing and interest in infants. Additionally we explored different methods of measuring interest in infants using self-reported fondness for babies, a forced choice adult versus infant paper-based preference task and a novel computer based attention task using adult and infant stimuli. In total 357 girls aged nine to 14 years participated in the study, which took place in schools. Participants completed the two interest in infants tasks before moving on to a childhood adversity questionnaire. Girls with more childhood adversity reported earlier ideal ages at parenthood. We found some evidence that, contrary to our predictions, girls with less childhood adversity were more interested in infants. There was no relationship between intended reproductive timing and interest in infants. The different measurements for interest in infants were only weakly related, if at all, highlighting the complexity of measuring this construct. Our findings suggest that rather than interest in infants being a mechanism for the effect of childhood adversity on early reproductive timing it might instead be an indicator of future reproductive strategies. PMID:24454778

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

    PubMed Central

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

    2012-01-01

    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 trajectory 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. PMID:22659062

  17. Childhood abuse or neglect is associated with increased vasomotor symptom reporting among midlife women

    PubMed Central

    Thurston, Rebecca C.; Bromberger, Joyce; Chang, Yuefang; Goldbacher, Edie; Brown, Charlotte; Cyranowski, Jill M.; Matthews, Karen A.

    2010-01-01

    Objectives This study tested the hypothesis that women exposed to childhood abuse or neglect would have an increased likelihood of reporting hot flashes and night sweats during the menopausal transition. Design This hypothesis was evaluated in 332 white and African American women participating in the Study of Women’s Health Across the Nation Mental Health Study, a prospective investigation of women transitioning through menopause. Childhood abuse and neglect were measured once with the Child Trauma Questionnaire. Vasomotor symptoms (any/none hot flashes, night sweats) were reported annually over 8 years. Associations between maltreatment and vasomotor symptoms were estimated with generalized estimating equations. Results Childhood abuse or neglect was associated with increased reporting of hot flashes (odds ratio = 1.73, 95% CI: 1.23–2.43) and night sweats (odds ratio = 1.75, 95% CI: 1.26–2.43) in age-adjusted models. Results persisted in multivariable models and across several types of abuse and neglect. Conclusions The experience of childhood abuse and neglect is associated with increased vasomotor symptom reporting in adulthood. The sequelae of childhood abuse and neglect may persist well into adulthood to influence the occurrence of vasomotor symptoms at midlife. PMID:18257140

  18. High fat diet-induced liver steatosis promotes an increase in liver mitochondrial biogenesis in response to hypoxia.

    PubMed

    Carabelli, Julieta; Burgueño, Adriana L; Rosselli, Maria Soledad; Gianotti, Tomas Fernández; Lago, Nestor R; Pirola, Carlos J; Sookoian, Silvia

    2011-06-01

    Mitochondrial DNA (mtDNA) copy number plays a key role in the pathophysiology of metabolic syndrome-related phenotypes, but its role in non-alcoholic fatty liver disease (NAFLD) is not well understood. We evaluated the molecular mechanisms that may be involved in the regulation of liver mtDNA content in a high-fat-induced rat model of NAFLD. In particular, we tested the hypothesis that liver mtDNA copy number is associated with liver expression of HIF-1α. Rats were given either standard chow diet (SCD, n = 10) or high-fat diet (HFD, n = 15) for 20 weeks. Subsequently, mtDNA quantification using nuclear DNA (nDNA) as a reference was carried out using real time quantitative PCR. HFD induced a significant increase in liver mtDNA/nDNA ratio, which significantly correlated with the liver triglyceride content (R: 0.29, P < 0.05). The liver mtDNA/nDNA ratio significantly correlated with the hepatic expression of HIF-1α mRNA (R: 0.37, P < 0.001); liver HIF-1α mRNA was significantly higher in the HFD group. In addition, liver cytochrome c oxidase subunit IV isoform 1 (COX4I1) mRNA expression was also positively correlated with liver mtDNA content. The hepatic expression of mRNA of transcriptional factors that regulate mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and PGC-1β, nuclear respiratory factor-1 (NRF-1), peroxisome proliferator-activated receptor δ and Tfam, was not associated with the liver mtDNA content. Neither hepatocyte apoptosis nor oxidative stress was involved in the HIF-1α-mediated increase in mtDNA copy number. In conclusion, we found that HFD promotes an increase in liver mitochondrial biogenesis in response to hypoxia via HIF-1α, probably to enhance the mitochondrial function as well as to accommodate the metabolic load. PMID:20629985

  19. High fat diet-induced liver steatosis promotes an increase in liver mitochondrial biogenesis in response to hypoxia

    PubMed Central

    Carabelli, Julieta; Burgueño, Adriana L; Rosselli, Maria Soledad; Gianotti, Tomas Fernández; Lago, Nestor R; Pirola, Carlos J; Sookoian, Silvia

    2011-01-01

    Abstract Mitochondrial DNA (mtDNA) copy number plays a key role in the pathophysiology of metabolic syndrome-related phenotypes, but its role in non-alcoholic fatty liver disease (NAFLD) is not well understood. We evaluated the molecular mechanisms that may be involved in the regulation of liver mtDNA content in a high-fat-induced rat model of NAFLD. In particular, we tested the hypothesis that liver mtDNA copy number is associated with liver expression of HIF-1α. Rats were given either standard chow diet (SCD, n= 10) or high-fat diet (HFD, n= 15) for 20 weeks. Subsequently, mtDNA quantification using nuclear DNA (nDNA) as a reference was carried out using real time quantitative PCR. HFD induced a significant increase in liver mtDNA/nDNA ratio, which significantly correlated with the liver triglyceride content (R: 0.29, P < 0.05). The liver mtDNA/nDNA ratio significantly correlated with the hepatic expression of HIF-1α mRNA (R: 0.37, P < 0.001); liver HIF-1α mRNA was significantly higher in the HFD group. In addition, liver cytochrome c oxidase subunit IV isoform 1 (COX4I1) mRNA expression was also positively correlated with liver mtDNA content. The hepatic expression of mRNA of transcriptional factors that regulate mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and PGC-1β, nuclear respiratory factor-1 (NRF-1), peroxisome proliferator-activated receptor δ and Tfam, was not associated with the liver mtDNA content. Neither hepatocyte apoptosis nor oxidative stress was involved in the HIF-1α-mediated increase in mtDNA copy number. In conclusion, we found that HFD promotes an increase in liver mitochondrial biogenesis in response to hypoxia via HIF-1α, probably to enhance the mitochondrial function as well as to accommodate the metabolic load. PMID:20629985

  20. 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…

  1. 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,…

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

    PubMed Central

    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 was divided into childhood-onset BP (age and BP onset <12 years; n = 192), adolescents with early-onset BP (age ≥12 years and BP onset <12 years; n = 136), and adolescents with late-onset BP (age and BP onset ≥12 years; n = 110). Lifetime family history of psychiatric illness was ascertained for first- and second-degree relatives through both direct interview of caretakers and the Family History Screen. Results After significant demographic and clinical factors were controlled for, children and adolescents with childhood-onset BP showed higher percentages of positive first-degree family history for depression, anxiety, attention-deficit/hyperactivity, conduct, and substance dependence disorders and suicidal behaviors compared with adolescents with late onset. Subjects with childhood-onset BP also showed elevated familial loading for depression and attention-deficit/hyperactive disorder in second-degree relatives. Conclusions These data support a model that postulates a higher density of familial risk for a broad range of psychopathology in childhood-onset BP. PMID:17242623

  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. 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.

  5. Calpain 2-mediated autophagy defect increases susceptibility of fatty livers to ischemia–reperfusion injury

    PubMed Central

    Zhao, Q; Guo, Z; Deng, W; Fu, S; Zhang, C; Chen, M; Ju, W; Wang, D; He, X

    2016-01-01

    Hepatic steatosis is associated with significant morbidity and mortality after liver resection and transplantation. This study focuses on the role of autophagy in regulating sensitivity of fatty livers to ischemia and reperfusion (I/R) injury. Quantitative immunohistochemistry conducted on human liver allograft biopsies showed that, the reduction of autophagy markers LC3 and Beclin-1 at 1 h after reperfusion, was correlated with hepatic steatosis and poor survival of liver transplant recipients. In animal studies, western blotting and confocal imaging analysis associated the increase in sensitivity to I/R injury with low autophagy activity in fatty livers. Screening of autophagy-related proteins showed that Atg3 and Atg7 expression levels were marked decreased, whereas calpain 2 expression was upregulated during I/R in fatty livers. Calpain 2 inhibition or knockdown enhanced autophagy and suppressed cell death. Further point mutation experiments revealed that calpain 2 cleaved Atg3 and Atg7 at Atg3Δ92–97 and Atg7Δ344–349, respectively. In vivo and in vitro overexpression of Atg3 or Atg7 enhanced autophagy and suppressed cell death after I/R in fatty livers. Collectively, calpain 2-mediated degradation of Atg3 and Atg7 in fatty livers increases their sensitivity to I/R injury. Increasing autophagy may ameliorate fatty liver damage and represent a valuable method to expand the liver donor pool. PMID:27077802

  6. Marginal Copper Deficiency Increases Liver Neutrophil Accumulation After Ischemia/Reperfusion in Rats

    PubMed Central

    Sakai, Nozomu; Shin, Thomas; Schuster, Rebecca; Blanchard, John; Lentsch, Alex B.; Johnson, William Thomas

    2010-01-01

    Copper deficiency can cause a host of major cardiovascular complications including an augmented inflammatory response through effects on both neutrophils and the microvascular endothelium. In the present study, we evaluated the effect of marginal copper deficiency on the neutrophilic response to hepatic ischemia/reperfusion injury, a condition that induces an inflammatory response. Male weanling Sprague–Dawley rats were fed purified diets which were either copper-adequate (6.3 mg/kg) or copper-marginal (1.62 mg/kg) for 4 weeks prior to undergoing 90 min of partial hepatic ischemia followed by 8 h of reperfusion. Liver injury was assessed by serum levels of alanine aminotransferase and by liver histology. Liver neutrophil accumulation was determined by tissue myeloperoxidase content. There was no significant difference in liver injury between copper-adequate and copper-marginal rats. However, liver neutrophil accumulation was significantly increased in copper-marginal rats. These findings were confirmed histologically. Liver expression of the adhesion molecule, intercellular adhesion molecule-1 (ICAM-1), was increased in copper-marginal rats compared to copper-adequate rats. The results suggest that neutrophil accumulation is increased through enhanced ICAM-1 expression in liver of copper-marginal rats after ischemia/reperfusion, but that this does not result in increased liver injury. PMID:20544302

  7. Parental neglect during childhood and increased risk of obesity in young adulthood.

    PubMed

    Lissau, I; Sørensen, T I

    1994-02-01

    The association of various features of family life with obesity in childhood is well established, but less is known about the effect of these influences on the risk of later obesity. In this prospective, population-based study, we examined the influence of parental care in childhood on the risk of obesity in the offspring in young adulthood. In 1974, 1258 pupils aged 9-10 years were randomly selected from the third grade of Copenhagen schools. Information on 987 pupils was obtained from the form teachers on family structure and the perceived support from the parents; school medical services reported on the child's general hygiene. 756 (86%) of the 881 eligible participants were followed up 10 years later. The influence of family factors in childhood on the risk of obesity (body-mass index > 95th centile) in young adulthood was estimated by odds ratios with control for age and body-mass index in 1974, sex, and social background. Family structure (biological or other parents and number of siblings) did not significantly affect the risk of adult obesity. Parental neglect greatly increased the risk in comparison with harmonious support (odds ratio 7.1 [95% CI 2.6-19.3]). Dirty and neglected children had a much greater risk of adult obesity than averagely groomed children (9.8 [3.5-28.2]). However, being an only child, receiving overprotective parental support, or being well-groomed had no effect. Parental neglect during childhood predicts a great risk of obesity in young adulthood, independent of age and body-mass index in childhood, sex, and social background. PMID:7905145

  8. Zinc monotherapy is effective in Wilson’s disease patients with mild liver disease diagnosed in childhood: a retrospective study

    PubMed Central

    2014-01-01

    Background Wilson’s disease (WD) evolves rapidly and is fatal if untreated. The treatment of WD patients with mild liver disease is not clearly defined. To address this issue, we evaluated long-term outcomes of three treatment regimens (D-penicillamine, zinc or both) in patients diagnosed in childhood. Methods We retrospectively evaluated efficacy, compliance and reasons for treatment discontinuation in 42 WD patients (median age at diagnosis: 6 years; median follow-up: 12 years) with mild liver disease. Treatment duration for each treatment block until a medication change or completion of follow-up was analyzed. Events of change of treatment were evaluated using Kaplan-Meier analysis. Results Total discontinuations due to treatment failure or adverse events were more frequent in patients receiving D-penicillamine (45%) or combination (36%) therapy than in patients receiving zinc (12%) (P = .001 and P = .02, respectively). Treatment failure was more frequent on D-penicillamine (28%) and combination therapy (36%) than on zinc (12%); the difference was statistically significant only between zinc and combination therapy (P = .03). First-line zinc monotherapy controlled WD-related liver disease in 13/15 patients (87%); the two subjects that failed on zinc were poor adherent. Zinc was effective in 3/5 (60%) patients that failed on D-penicillamine and combination regimens. All 15 D-penicillamine responders that switched to zinc had good control of liver disease at a median follow-up of 13.1 years. Among 6 D-penicillamine non-responders that switched to zinc, 4 (67%) responded. At follow-up completion, only 5/42 (12%) patients failed. Adverse event-induced discontinuation was significantly more frequent in patients on D-penicillamine than in patients receiving zinc (P = .03). Conclusions Zinc monotherapy is effective in controlling WD-related liver disease both as first-line and as maintenance treatment in patients with mild liver disease diagnosed in

  9. 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. PMID:20838830

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

    PubMed

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

    1993-09-01

    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. PMID:8102720

  11. 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

  12. 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

  13. 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. PMID:14668265

  14. 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. PMID:24691161

  15. 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.…

  16. 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.

  17. Nod2 deficiency protects mice from cholestatic liver disease by increasing renal excretion of bile acids

    PubMed Central

    Wang, Lirui; Hartmann, Phillipp; Haimerl, Michael; Bathena, Sai P.; Sjöwall, Christopher; Almer, Sven; Alnouti, Yazen; Hofmann, Alan F.; Schnabl, Bernd

    2014-01-01

    Background & aims Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis. Methods We studied experimental cholestatic liver disease induced by bile duct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2−/− mice. Results Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2−/− mice than wild type mice following bile duct ligation for 3 weeks. In contrast to wild type mice, Nod2−/− mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1β in a Nod2 dependent fashion. Conclusions Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte. PMID:24560660

  18. Increased P-glycoprotein messenger RNA stability in rat liver tumors in vivo.

    PubMed

    Lee, C H; Bradley, G; Ling, V

    1998-10-01

    P-glycoproteins (Pgp) are comprised of a small family of plasma membrane proteins whose abundance in cultured cells is often associated with the multidrug resistance phenotype. Overexpression of Pgp has been observed in many types of human cancers, but the molecular basis for this overexpression has not been established. We have used primary monolayer cultures of adult rat hepatocytes and a stepwise model of rat liver carcinogenesis to study the regulation of Pgp gene expression. We observed a marked overexpression of Pgp, specifically the class II Pgp, in both systems. In addition, we observed that a number of unrelated genes including alpha-tubulin, beta-actin, gamma-actin, cytokeratin 8, cytokeratin 18, and c-myc are overexpressed in cultured hepatocytes, and they are also overexpressed during liver carcinogenesis and in transplantable tumors. Nuclear run-on assays showed no increase in the transcriptional activity of Pgp genes in transplantable liver tumors compared to normal liver. Studies of in vivo mRNA stability, however, revealed that all three Pgp mRNAs were relatively stable in transplantable liver tumors (t(1/2) > 12 h), in contrast to what was found in normal liver (t(1/2) < 2 h). In addition, mRNA for several other genes, including alpha-tubulin, c-myc, and cyclin D1, all appear to be stabilized in the tumors. These findings suggest that the overexpression of Pgp genes in rat liver tumors may be the result of a mechanism involving stabilization of a diverse group of mRNAs. PMID:9731740

  19. [Complication management after liver transplantation. Increasing patient safety by standardized approach and interdisciplinary cooperation].

    PubMed

    Houben, P; Gotthardt, D N; Radeleff, B; Sauer, P; Büchler, M W; Schemmer, P

    2015-02-01

    The interdisciplinary management of postoperative complications in liver transplantation is of extreme importance. Due to organ shortage and prioritization of the most severely ill recipients in the model for end-stage liver disease (MELD)-based allocation, both donor and recipient associated morbidity are increasing. An interdisciplinary, structured monitoring concept is essential for the timely identification and specific treatment of postoperative complications. Interdisciplinary clinical rounds, laboratory testing and Doppler ultrasound monitoring of the graft perfusion are as important as comprehensive anti-infection prophylaxis and immunosuppression. Arterial perfusion disorders of any kind, biliary complications and postoperative fluid accumulation demand individualized therapeutic concepts. In summary, the success of liver transplantation depends on the communication and coordinated interdisciplinary cooperation of all disciplines involved. PMID:25604306

  20. Hepatoprotectant Ursodeoxycholyl Lysophosphatidylethanolamide Increasing Phosphatidylcholine Levels as a Potential Therapy of Acute Liver Injury

    PubMed Central

    Chamulitrat, Walee; Zhang, Wujuan; Xu, Weihong; Pathil, Anita; Setchell, Kenneth; Stremmel, Wolfgang

    2012-01-01

    It has been long known that hepatic synthesis of phosphatidylcholine (PC) is depressed during acute such as carbon tetrachloride-induced liver injury. Anti-hepatotoxic properties of PC as liposomes have been recognized for treatment of acute liver damage. Ursodeoxycholate (UDCA) is a known hepatoprotectant in stabilizing cellular membrane. For therapeutic management of liver injury, we coupled UDCA with a phospholipid known as ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE). UDCA-LPE has been shown to first-in-class hepatoprotectant being superior to UDCA or PC. It inhibits mitochondrial damage and apoptosis, elicits survival signaling pathway, and promotes regeneration of hepatocytes. We herein report that a unique contribution of UDCA-LPE in increasing concentrations of PC in vitro and in vivo. UDCA-LPE-treated hepatocytes contained significantly increased PC levels. UDCA-LPE underwent the hydrolysis to LPE which was not the precursor of the increased PC. The levels of PC in the liver and blood were increased rapidly after intraperitoneally administration UDCA-LPE, and were found to be sustained even after 24 h. Among PC synthesis genes tested, UDCA-LPE treatment of mouse hepatocytes increased transcription of CDP-diacylglycerol synthase 1 which is an enzyme catalyzing phosphatidic acid to generate intermediates for PC synthesis. Thus, UDCA-LPE as a hepatoprotectant was able to induce synthesis of protective PC which would supplement for the loss of PC occurring during acute liver injury. This property has placed UDCA-LPE as a candidate agent for therapy of acute hepatotoxicity such as acetaminophen poisoning. PMID:22363296

  1. 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. PMID:19488046

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

    PubMed Central

    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.

    2016-01-01

    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 Hbbth1/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. PMID:26635037

  3. 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

  4. 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. PMID:22031624

  5. 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

  6. Liver.

    PubMed

    Kim, W R; Lake, J R; Smith, J M; Skeans, M A; Schladt, D P; Edwards, E B; Harper, A M; Wainright, J L; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    The median waiting time for patients with MELD ≥ 35 decreased from 18 days in 2012 to 9 days in 2014, after implementation of the Share 35 policy in June 2013. Similarly, mortality among candidates listed with MELD ≥ 35 decreased from 366 per 100 waitlist years in 2012 to 315 in 2014. The number of new active candidates added to the pediatric liver transplant waiting list in 2014 was 655, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) continued to decline, 401 active and 173 inactive. The number of deceased donor pediatric liver transplants peaked at 542 in 2008 and was 478 in 2014. The number of living donor liver pediatric transplants was 52 in 2014; most were from donors closely related to the recipients. Graft survival continued to improve among pediatric recipients of deceased donor and living donor livers. PMID:26755264

  7. 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

  8. Dietary alpha-linolenic acid increases brain but not heart and liver docosahexaenoic acid levels.

    PubMed

    Barceló-Coblijn, Gwendolyn; Collison, Lauren W; Jolly, Christopher A; Murphy, Eric J

    2005-08-01

    Fish oil-enriched diets increase n-3 FA in tissue phospholipids; however, a similar effect by plant-derived n-3 FA is poorly defined. To address this question, we determined mass changes in phospholipid FA, individual phospholipid classes, and cholesterol in the liver, heart, and brain of rats fed diets enriched in flax oil (rich in 18:3n-3), fish oil (rich in 22:6n-3 and 20:5n-3), or safflower oil (rich in 18:2n-6) for 8 wk. In the heart and liver phospholipids, 22:6n-3 levels increased only in the fish oil group, although rats fed flax oil accumulated 20:5n-3 and 22:5n-3. However, in the brain, the flax and fish oil diets increased the phospholipid 22:6n-3 mass. In all tissues, these diets decreased the 20:4n-6 mass, although the effect was more marked in the fish oil than in the flax oil group. Although these data do not provide direct evidence for 18:3n-3 elongation and desaturation by the brain, they demonstrate that 18:3n-3-enriched diets reduced tissue 20:4n-6 levels and increased cellular n-3 levels in a tissue-dependent manner. We hypothesize, based on the lack of increased 22:6n-3 but increased 18:3n-3 in the liver and heart, that the flax oil diet increased circulating 18:3n-3, thereby presenting tissue with this EFA for further elongation and desaturation. PMID:16296397

  9. 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

  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. 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. PMID:24757127

  12. 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

  13. 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. PMID:20416398

  14. Decline in Physical Fitness From Childhood to Adulthood Associated With Increased Obesity and Insulin Resistance in Adults

    PubMed Central

    Dwyer, Terence; Magnussen, Costan G.; Schmidt, Michael D.; Ukoumunne, Obioha C.; Ponsonby, Anne-Louise; Raitakari, Olli T.; Zimmet, Paul Z.; Blair, Steven N.; Thomson, Russell; Cleland, Verity J.; Venn, Alison

    2009-01-01

    OBJECTIVE To examine how fitness in both childhood and adulthood is associated with adult obesity and insulin resistance. RESEARCH DESIGN AND METHODS A prospective cohort study set in Australia in 2004–2006 followed up a cohort of 647 adults who had participated in the Australian Schools Health and Fitness Survey in 1985 and who had undergone anthropometry and cardiorespiratory fitness assessment during the survey. Outcome measures were insulin resistance and obesity, defined as a homeostasis model assessment index above the 75th sex-specific percentile and BMI ≥30 kg/m2, respectively. RESULTS Lower levels of child cardiorespiratory fitness were associated with increased odds of adult obesity (adjusted odds ratio [OR] per unit decrease 3.0 [95% CI 1.6–5.6]) and insulin resistance (1.7 [1.1–2.6]). A decline in fitness level between childhood and adulthood was associated with increased obesity (4.5 [2.6–7.7]) and insulin resistance (2.1 [1.5–2.9]) per unit decline. CONCLUSIONS A decline in fitness from childhood to adulthood, and by inference a decline in physical activity, is associated with obesity and insulin resistance in adulthood. Programs aimed at maintaining high childhood physical activity levels into adulthood may have potential for reducing the burden of obesity and type 2 diabetes in adults. PMID:19106381

  15. 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. PMID:25749341

  16. 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. PMID:25725782

  17. 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

  18. Large intestine permeability is increased in patients with compensated liver cirrhosis.

    PubMed

    Pijls, Kirsten E; Koek, Ger H; Elamin, Elhaseen E; de Vries, Hanne; Masclee, Ad A M; Jonkers, Daisy M A E

    2014-01-01

    Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Increased intestinal permeability has been found in patients with liver cirrhosis, but data on small and large intestine permeability and tight junctions (TJs) in patients with compensated cirrhosis are scarce. We aimed to investigate both small and large intestine permeability in patients with stable compensated cirrhosis compared with healthy controls and evaluated the expression of TJ proteins in mucosal biopsies at duodenal and sigmoid level. Intestinal permeability was assessed in 26 patients with compensated cirrhosis and 27 matched controls using a multisugar test. Duodenal and sigmoid biopsies were available from a subgroup for analyses of gene transcription and expression of key TJ proteins by qRT-PCR and ELISA, respectively. Median 0-5-h urinary sucrose excretion and lactulose/rhamnose ratio were comparable between patients with compensated cirrhosis and controls, whereas 5-24-h urinary sucralose/erythritol ratio was increased in these patients. Downregulation of gene transcription was found for claudin-3 in duodenal biopsies and claudin-4 in sigmoid biopsies, and at the protein level occludin expression was significantly increased in both duodenal and sigmoid biopsies. This study shows that gastroduodenal and small intestine permeability are not altered, whereas large intestine permeability is increased in patients with stable compensated cirrhosis. Only limited alterations were found regarding the expression of TJ proteins in both the small and large intestine. PMID:24264047

  19. 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

  20. Folate supplementation increases genomic DNA methylation in the liver of elder rats.

    PubMed

    Choi, Sang-Woon; Friso, Simonetta; Keyes, Mary K; Mason, Joel B

    2005-01-01

    The availability of folate is implicated as a determinant of DNA methylation, a functionally important feature of DNA. Nevertheless, when this phenomenon has been examined in the rodent model, the effect has not always been observed. Several reasons have been postulated for the inconsistency between studies: the rodent is less dependent on folate as a methyl source than man; juvenile animals, which most studies use, are more resistant to folate depletion than old animals; methods to measure genomic DNA methylation might not be sensitive enough to detect differences. We therefore examined the relationship between folate and genomic DNA methylation in an elder rat model with a newly developed method that can measure genomic DNA methylation sensitively and precisely. Thirty-nine 1-year-old rats were divided into three groups and fed a diet containing 0, 4.5 or 18 mumol folate/kg (folate-deplete, -replete and -supplemented groups, respectively). Rats were killed at 8 and 20 weeks. At both time points, mean liver folate concentrations increased incrementally between the folate-deplete, -replete and -supplemented rats (P for trend <0.001) and by 20 weeks hepatic DNA methylation also increased incrementally between the folate-deplete, -replete and -supplemented rats (P for trend=0.025). At both time points folate-supplemented rats had significantly increased levels of DNA methylation compared with folate-deplete rats (P<0.05). There was a strong correlation between hepatic folate concentration and genomic DNA methylation in the liver (r 0.48, P=0.004). In the liver of this animal model, dietary folate over a wide range of intakes modulates genomic DNA methylation. PMID:15705222

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

    PubMed Central

    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

    2016-01-01

    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/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. PMID:27432511

  2. Food restriction prevents an age-associated increase in rat liver beta-adrenergic receptors

    SciTech Connect

    Dax, E.M.; Ingram, D.K.; Partilla, J.S.; Gregerman, R.I.

    1989-05-01

    In male Wistar rats fed ad libitum (24% protein, 4.5 Kcal/gm), the (/sup 125/I)iodopindolol binding capacity of the beta-adrenergic receptors in liver of 24-month-old animals is 3-4 times greater than that of 6-month-old counterparts. In rats fed the same diet, on alternate days from weaning, the receptor capacity did not increase significantly between 6 and 24 months (10.20 +/- 0.55 vs 9.20 +/- 0.72 fmol/mg) or between 24 and 30 months. This was not due to acute dietary deprivation, as rats food-restricted for only 2 weeks, at 23.5 months of age, also showed elevated receptor capacities compared to 6-month-old ad libitum fed animals. Moreover, intermittent feeding produced no significant effects among 6-month-old animals, whether restricted since weaning or for two weeks prior to sacrifice. Many biochemical parameters that decrease with aging in rats fed ad libitum are prevented by dietary restriction. Our results demonstrate that a reproducible biochemical process that increases with aging is also prevented with dietary restriction. The age-related, liver beta-receptor increase may be a potentially reliable marker for studying biochemical perturbations that modify life span.

  3. 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…

  4. 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…

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

    PubMed

    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

  6. 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…

  7. 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…

  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. 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…

  10. 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

    2016-03-01

    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. PMID:26851372

  11. 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

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

    PubMed

    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

  13. Increased All-Cause, Liver, and Cardiac Mortality among Hepatitis C Virus-seropositive Blood Donors

    PubMed Central

    Guiltinan, Anne M.; Kaidarova, Zhanna; Custer, Brian; Orland, Jennie; Strollo, Angela; Cyrus, Sherri; Busch, Michael P.; Murphy, Edward L.

    2010-01-01

    Hospital-based studies suggest that hepatitis C virus (HCV) infection causes frequent cirrhosis, hepatocellular carcinoma, and mortality, but epidemiologic studies have shown less morbidity and mortality. The authors performed a retrospective cohort study of 10,259 recombinant immunoblot assay-confirmed, HCV antibody-positive (HCV+), allogeneic blood donors from 1991 to 2002 and 10,259 HCV antibody-negative (HCV−) donors matched for year of donation, age, gender, and Zone Improvement Plan Code (ZIP Code). Vital status through 2003 was obtained from the US National Death Index, and hazard ratios with 95% confidence intervals were calculated by survival analysis. After a mean follow-up of 7.7 years, there were 601 (2.92%) deaths: 453 HCV+ and 148 HCV− (hazard ratio (HR) = 3.13, 95% confidence interval (CI): 2.60, 3.76). Excess mortality in the HCV+ group was greatest in liver-related (HR = 45.99, 95% CI: 11.32, 186.74), drug- or alcohol-related (HR = 10.81, 95% CI: 4.68, 24.96), and trauma/suicide (HR = 2.99, 95% CI: 2.05, 4.36) causes. There was also an unexpected increase in cardiovascular mortality among the HCV+ donors (HR = 2.21, 95% CI: 1.41, 3.46). HCV infection is associated with a significant, threefold increase in overall mortality among former blood donors, including significantly increased mortality from liver and cardiovascular causes. High rates of mortality from drug/alcohol and trauma/suicide causes are likely due to lifestyle factors and may be at least partially preventable. PMID:18203734

  14. Impaired Gallbladder Motility and Increased Gallbladder Wall Thickness in Patients with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Colak, Yasar; Bozbey, Gulcin; Erim, Tolga; Caklili, Ozge Telci; Ulasoglu, Celal; Senates, Ebubekir; Mutlu, Hasan Huseyin; Mesci, Banu; Doğan, Mehmet Sait; Tasan, Guralp; Enc, Feruze Yilmaz; Tuncer, Ilyas

    2016-01-01

    Background/Aims Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Along with the increase in the incidence of NAFLD and associated obesity, an increase in gallbladder disease (GD) has been noted. This has led to the identification of a new disease entity called fatty GD. There is a gap in the literature on the dynamics of gallbladder function in patients with NAFLD. Methods An observational case-control study, a total of 50 patients with biopsy proven NAFLD without gallbladder stone/sludge and 38 healthy comparison subjects were enrolled. Fasting, postprandial gallbladder volumes (PGV), gallbladder ejection fraction (GEF), and fasting gallbladder wall thickness (FGWT) were measured by real-time 2-dimensional ultrasonography. Results Fasting gallbladder wall thickness, fasting gallbladder volumes and PGV were significantly higher in patients with NAFLD than control subjects (P < 0.001, P = 0.006, and P < 0.001, respectively). Gallbladder ejection fraction was significantly lower in the NAFLD group than the controls (P = 0.008). The presence of NAFLD was an independent predictor for GEF, PGV, and FGWT. Also, steatosis grade was an independent predictor for GEF, and GEF was significantly lower in the nonalcoholic steatohepatitis (NASH) subgroup than the controls. Conclusions Gallbladder dysfunction and increase in gallbladder wall thickness exists in asymptomatic (without stone/sludge and related symptoms) patients with NAFLD and are useful in identifying fatty GD. Measurement of these variables in NAFLD patients may be useful in identifying those at higher risk for GD. PMID:26932908

  15. Zolpidem Use Associated With Increased Risk of Pyogenic Liver Abscess: A Case-Control Study in Taiwan.

    PubMed

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

    2015-08-01

    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

  16. Transforming growth factor beta mRNA increases during liver regeneration: a possible paracrine mechanism of growth regulation.

    PubMed Central

    Braun, L; Mead, J E; Panzica, M; Mikumo, R; Bell, G I; Fausto, N

    1988-01-01

    Transforming growth factor beta (TGF-beta) is a growth factor with multiple biological properties including stimulation and inhibition of cell proliferation. To determine whether TGF-beta is involved in hepatocyte growth responses in vivo, we measured the levels of TGF-beta mRNA in normal liver and during liver regeneration after partial hepatectomy in rats. TGF-beta mRNA increases in the regenerating liver and reaches a peak (about 8 times higher than basal levels) after the major wave of hepatocyte cell division and mitosis have taken place and after the peak expression of the ras protooncogenes. Although hepatocytes from normal and regenerating liver respond to TGF-beta, they do not synthesize TGF-beta mRNA. Instead, the message is present in liver nonparenchymal cells and is particularly abundant in cell fractions enriched for endothelial cells. TGF-beta inhibits epidermal growth factor-induced DNA synthesis in vitro in hepatocytes from normal or regenerating liver, although the dose-response curves vary according to the culture medium used. We conclude that TGF-beta may function as the effector of an inhibitory paracrine loop that is activated during liver regeneration, perhaps to prevent uncontrolled hepatocyte proliferation. Images PMID:3422749

  17. 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. PMID:21835690

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

    PubMed

    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 P Y

    2014-04-01

    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

  19. 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

  20. 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.

  1. Increased P-selectin gene expression in the liver vasculature and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock.

    PubMed

    Essani, N A; Fisher, M A; Simmons, C A; Hoover, J L; Farhood, A; Jaeschke, H

    1998-03-01

    We studied the role of P-selectin, an adhesion molecule known to be important for neutrophil localization to sites of inflammation, in a model of inflammatory liver injury. Male C3Heb/FeJ (ET-sensitive) mice treated with 700 mg/kg galactosamine and 100 microg/kg Salmonella abortus equi endotoxin (Gal/ET), murine tumor necrosis factor alpha (TNF-alpha, 15 microg/kg), or interleukin-1 (IL-1, 13-23 microg/kg), showed increased P-selectin mRNA levels in the liver. In contrast, C3H/HeJ (ET-resistant) mice responded only to cytokines with P-selectin mRNA formation. Whereas no P-selectin expression was detectable in control livers, there was temporary staining of endothelium in large blood vessels but not in sinusoids between 3 and 5 h after ET, TNF-alpha, or IL-1 treatment. Severe liver injury induced by Gal/ET at 7 h was not inhibited by an anti-P-selectin antibody in C3Heb/FeJ mice or in P-selectin-deficient animals. Sequestration of neutrophils in sinusoids, i.e. those neutrophils that have been identified as critical for the injury, was not affected by the antibody or in P-selectin-deficient mice. However, the temporary margination in portal and post-sinusoidal venules was reduced by 75% in anti-P-selectin antibody-treated animals and by 51% in P-selectin-deficient mice. We conclude that hepatic P-selectin gene transcription in vivo involves cytokines. However, blocking P-selectin neither attenuated sinusoidal neutrophil sequestration nor prevented neutrophil-induced liver injury during endotoxin shock but attenuated neutrophil margination in larger vessels. Thus, our data demonstrate similarities and fundamental differences in the requirement for adhesion molecules to localize neutrophils in the liver vasculature compared to other organs during an inflammatory response. PMID:9500515

  2. POST-TRANSPLANT HYPERGLYCEMIA IS ASSOCIATED WITH INCREASED RISK OF LIVER ALLOGRAFT REJECTION

    PubMed Central

    Wallia, Amisha; Parikh, Neehar D; Molitch, Mark E; Mahler, Eileen; Tian, Lu; Huang, Jie Jenny; Levitsky, Josh

    2010-01-01

    BACKGROUND Intensive glycemic control has been shown to positively impact outcomes in an intensive care setting. Whether this practice is beneficial after liver transplantation (LT) is not known. METHODS A retrospective review of patients undergoing LT from 2/02-07/04 was conducted to analyze the association between peri-operative hyperglycemia and outcomes after LT. Covariates included pre-existing diabetes, mean glucose three months pre-LT, need for insulin drip post-LT, mean total glucose during the post-LT hospitalization, age, gender, type of transplant, and MELD score. Outcomes within one year of LT included rejection, infection, re-hospitalization, prolonged ventilation, and patient/graft survival. RESULTS 113 LT and 31 liver-kidney recipients were included. By multivariate logistic regression adjusting for covariates, the rejection rate was significantly lower for patients with postoperative glucose levels < 200 mg/dL (n=114) vs. > 200 mg/dL (n=30) (OR 0.055, 95%CI [0.0154, 0.200], p<0.001). The need for prolonged ventilation was more common in patients with glucose < 200 vs. > 200 mg/dL (OR 4.30, 95%CI [1.284, 14.388], p=0.018). While other outcomes, infection, re-hospitalization, patient/graft survival, were not different among the glucose control groups, rejection was associated with increased re-hospitalizations and infections. CONCLUSION Our data demonstrate an association between immediate post-transplant glycemic control and the development of subsequent rejection. Prospective trials investigating the effects of perioperative glycemic control on outcomes and morbidity after LT are warranted. PMID:20098286

  3. Gastroesophageal Reflux Disease Increases Infant Acute Respiratory Illness Severity, but not Childhood Asthma.

    PubMed

    Valet, Robert S; Carroll, Kecia N; Gebretsadik, Tebeb; Minton, Patricia A; Woodward, Kimberly B; Liu, Zhouwen; Hartert, Tina V

    2014-03-01

    It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronchiolitis severity or childhood asthma inception. Four hundred thirty-two infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection were studied. The primary exposure was the parental report of a previous GERD diagnosis. Outcomes included bronchiolitis severity at initial presentation and childhood asthma diagnosis at age 4. Infants with parentally reported GERD had a higher bronchiolitis severity score (range=0-12, clinically significant difference=0.5), indicating more severe disease, than infants without reported GERD (median 5.5 [interquartile range 3.5-9.0] among those with reported GERD versus 4.0 [1.0-7.0] among those without, P=0.005). This association persisted after adjusting for infant age, race, gender, and secondhand smoke exposure by a propensity score (adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.46, P=0.02). The parental report of GERD during infancy was not associated with the parental report of asthma diagnosis at age 4. GERD during infancy may contribute to acute respiratory illness severity, but is not associated with asthma diagnosis at age 4. Future prospective studies are needed to confirm these findings. PMID:24669353

  4. Nitric oxide (NO) inhibits antigen-stimulated increases in vasoconstriction and glycogenolysis in perfused livers derived from sensitized rats

    SciTech Connect

    Hines, K.L.; Bates, J.N.; Fisher, R.A. )

    1991-03-11

    Recent studies in the authors laboratory demonstrated that infusion of antigen into perfused livers from sensitized rats produces increases in hepatic portal pressure, increases in hepatic glucose output and decreases in hepatic oxygen consumption. In the present study, effects of NO on these hepatic responses to antigen challenge were investigated. Infusion of NO into perfused livers from sensitized rats attenuated ovalbumin induced increases in hepatic portal pressure and glucose output approximately 85% and 90%, respectively, and abolished ovalbumin-induced decreases in hepatic oxygen consumption. The duration of ovalbumin-stimulated increases in hepatic portal pressure was reduced nearly 90% by NO. Similarly, infusion of NO into perfused livers from sensitized rats inhibited increases in hepatic portal pressure and glucose output in response to platelet-activating factor (PAF) nearly 80 and 90%, respectively. In contrast, NO inhibited completely hepatic vasoconstriction in response to phenylephrine without altering glycogenolytic responses to this {alpha}-adrenergic agonist. These results provide evidence for regulatory effects of NO on hemodynamic and glycogenolytic responses to antigen in perfused livers from sensitized rats. These observations support previous findings which suggest that hepatic responses to sensitizing antigen may be mediated by PAF or other autacoid mediators which stimulate glycogenolysis in liver by indirect mechanisms involving hepatic vasoconstriction.

  5. 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

  6. SIRT1 increases YAP- and MKK3-dependent p38 phosphorylation in mouse liver and human hepatocellular carcinoma

    PubMed Central

    Zhang, Xiao; Qiao, Yongxia; Liu, Xiangfan; Chang, Yefei; Yu, Yongchun; Sun, Fenyong; Wang, Jiayi

    2016-01-01

    Both oncoprotein and tumor-suppressor activity have been reported for SIRTUIN1 (SIRT1) and p38 in many types of cancer. The effect of SIRT1 on p38 phosphorylation (p-p38) remains controversial and may be organ- and cell-specific. We found that SIRT1 is essential for maintaining liver size and weight in mice. SIRT1 levels were elevated in human HCC compared to adjacent normal liver tissue, and its expression correlated positively with p-p38 levels. Additionally, SIRT1-activated p38 increased liver cancer malignancy. SIRT1 increased phosphorylation and nuclear accumulation of p38, possibly by increasing MKK3 expression. SIRT1 also induced YAP expression, which in turn increased MKK3 transcription. Positive correlations between SIRT1, YAP, MKK3, and p-p38 levels indicate that blocking their activity may prove helpful in treating HCC. PMID:26824501

  7. 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

  8. 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.

  9. Appendectomy correlates with increased risk of pyogenic liver abscess: A population-based cohort study in Taiwan.

    PubMed

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

    2016-06-01

    Little is known on the association between appendectomy and pyogenic liver abscess. The objective of this study was to investigate the association between appendectomy and the risk of pyogenic liver abscess in Taiwan.This population-based retrospective cohort study was conducted using the hospitalization dataset of the Taiwan National Health Insurance Program. There were 212,530 subjects age 20 to 84 years with newly diagnosed appendectomy as the appendectomy group since 1998 to 2010, and 850,099 randomly selected subjects without appendectomy as the nonappendectomy group. Both appendectomy and nonappendectomy groups were matched with sex, age, comorbidities, and index year of diagnosing appendectomy. The incidence of pyogenic liver abscess at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was applied to investigate the hazard ratio (HR) and 95% confidence interval (CI) for risk of pyogenic liver abscess associated with appendectomy and other comorbidities including alcoholism, biliary stone, chronic kidney disease, chronic liver diseases, and diabetes mellitus.The overall incidence of pyogenic liver abscess was 1.73-fold greater in the appendectomy group than that in the nonappendectomy group (3.85 vs 2.22 per 10,000 person-years, 95% CI 1.71, 1.76). The multivariable regression analysis disclosed that the adjusted HR of pyogenic liver abscess was 1.77 for the appendectomy group (95% CI 1.59, 1.97), when compared with the nonappendectomy group.Appendectomy is associated with increased hazard of pyogenic liver abscess. Further studies remain necessary to confirm our findings. PMID:27368018

  10. SR-A and SREC-I binding peptides increase HDAd-mediated liver transduction

    PubMed Central

    Piccolo, Pasquale; Annunziata, Patrizia; Mithbaokar, Pratibha; Brunetti-Pierri, Nicola

    2014-01-01

    Helper-dependent adenoviral (HDAd) vectors can mediate long-term, high-level transgene expression from transduced hepatocytes without inducing chronic toxicity. However, vector therapeutic index is narrow because of a toxic acute response with potentially lethal consequences elicited by high vector doses. Kupffer cells and liver sinusoidal endothelial cells (LSECs) are major barriers to efficient hepatocyte transduction. We investigated two small peptides (PP1 and PP2) developed by phage display to block scavenger receptor type A (SR-A) and scavenger receptor expressed on endothelial cells type I (SREC-I) respectively, for enhancement of HDAd-mediated hepatocyte transduction efficiency. Pre-incubation of J774A.1 macrophages with either PP1 or PP2 prior to HDAd infection significantly reduced viral vector uptake. In vivo, fluorochrome-conjugated PP1 and PP2 injected intravenously into mice co-localized with both CD68 and CD31 on Kupffer cells and LSECs, respectively. Compared to saline pre-treated animals, intravenous injections of both peptides prior to the injection of an HDAd resulted in up to 3.7- and 2.9-fold increase of hepatic transgene expression with PP1 and PP2, respectively. In addition to hepatocyte transduction, compared to control saline injected mice, pre-treatment with either peptide resulted in no increased levels of serum interleukin-6 (IL-6), the major marker of adenoviral vector acute toxicity. In summary, we developed small peptides that significantly increase hepatocyte transduction efficacy and improve HDAd therapeutic index with potential for clinical applications. PMID:25119377

  11. Increased HO-1 Levels Ameliorate Fatty Liver Development Through a Reduction of Heme and Recruitment of FGF21

    PubMed Central

    Hinds, Terry D.; Sodhi, Komal; Meadows, Charles; Fedorova, Larisa; Puri, Nitin; Kim, Dong Hyun; Peterson, Stephen J.; Shapiro, Joseph; Abraham, Nader G.; Kappas, Attallah

    2013-01-01

    Objective Obese leptin deficient (ob/ob) mice are a model of adiposity that displays increased levels of fat, glucose and liver lipids. Our hypothesis is that HO-1 overexpression ameliorates fatty liver development. Design and Methods Obese mice were administered cobalt protoporphyrin (CoPP) and stannic mesoporphyrin (SnMP) for 6 weeks. Heme, HO-1, HO activity, PGC1α, FGF21, glycogen content and lipogenesis were assessed. Results CoPP administration increased hepatic HO-1 protein levels and HO activity, decreased hepatic heme, body weight gain, glucose levels and resulted in decreased steatosis. Increased levels of HO-1 produced a decrease in lipid droplet size, FAS levels involving recruitment of FGF21, PPARα and Glut 1. These beneficial effects were reversed by inhibition of HO activity. Conclusion Increased levels of HO-1 and HO activity reduced the levels of obesity by reducing hepatic heme and lipid accumulation. These changes were manifested by decreases in cellular heme, increases in FGF21, glycogen content and fatty liver. The beneficial effect of HO-1 induction results from an increase in PPARα and FGF21 levels and a decrease in PGC1α, levels they were reversed by SnMP. Low levels of HO-1 and HO activity are responsible for fatty liver. PMID:23839791

  12. Effects of Increased Von Willebrand Factor Levels on Primary Hemostasis in Thrombocytopenic Patients with Liver Cirrhosis

    PubMed Central

    Wannhoff, Andreas; Müller, Oliver J.; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A.; Gotthardt, Daniel N.

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180±62 s with Col-Epi and 160±70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥150/nL and hematocrit ≥27.0%, pathological PFA-100 results were found. In thrombocytopenic (<150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3±235.9% vs. 338.7±151.6%, P = 0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future. PMID

  13. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

    PubMed

    Wannhoff, Andreas; Müller, Oliver J; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A; Gotthardt, Daniel N

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (< 150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3 ± 235.9% vs. 338.7 ± 151.6%, P = 0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future

  14. 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. PMID:24779467

  15. 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

  16. Overexpression of transforming growth factor-alpha causes liver enlargement and increased hepatocyte proliferation in transgenic mice.

    PubMed Central

    Webber, E. M.; Wu, J. C.; Wang, L.; Merlino, G.; Fausto, N.

    1994-01-01

    constitutive overexpression of TGF-alpha causes increased hepatocyte proliferation and liver enlargement in young animals and is associated with a delay in the establishment of hepatic polyploidy. These findings as well as the response of transgenic mice to partial hepatectomy show that constitutive overexpression of TGF-alpha initially caused increased but regulated hepatocyte proliferation which in older animals was compensated in part by a faster cell turnover. At 8 to 10 months of age, proliferative activity may become constitutive in some TGF-alpha expressing hepatocytes.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 4 PMID:8053497

  17. Hypolipidemic action of the SERM acolbifene is associated with decreased liver MTP and increased SR-BI and LDL receptors.

    PubMed

    Lemieux, Christian; Gélinas, Yves; Lalonde, Josée; Labrie, Fernand; Cianflone, Katherine; Deshaies, Yves

    2005-06-01

    This study aimed to identify the mechanisms of the hypolipidemic action of the selective estrogen receptor modulator (SERM) acolbifene (ACOL). Four weeks of treatment with ACOL reduced fasting and postprandial plasma triglycerides (TGs), an effect associated with lower VLDL-TG secretion rate (-25%), and decreased mRNA of microsomal triglyceride transfer protein (MTP; -29%). ACOL increased liver TG concentration (+100%) and amplified the feeding-induced increase in the master lipogenic regulators sterol-regulatory element binding protein-1a (SREBP-1a) and SREBP-1c. ACOL decreased total, HDL, and non-HDL cholesterol (CHOL) by 50%. SREBP-2 mRNA and HMG-CoA reductase activity were minimally affected by ACOL. However, in the fasted state, liver concentration of scavenger receptor class B type I (SR-BI) protein, but not mRNA, was 3-fold higher in ACOL-treated than in control animals and correlated with plasma HDL-CHOL levels (r = 0.80, P < 0.002). Liver LDL receptor (LDLR) protein, but not mRNA, was increased 2-fold by ACOL, independently of the nutritional status. This study demonstrates that ACOL possesses the unique ability among SERMs to reduce VLDL-TG secretion, likely by reducing MTP expression, and strongly suggests that the robust hypocholesterolemic action of ACOL is related to increased removal of CHOL from the circulation as a consequence of enhanced liver SR-BI and LDLR abundance. PMID:15741653

  18. GLUT2 proteins and PPARγ transcripts levels are increased in liver of ovariectomized rats: reversal effects of resistance training

    PubMed Central

    Tomaz, Luciane M.; Barbosa, Marina R.; Farahnak, Zahra; Lagoeiro, Cristiani G.; Magosso, Natalia S.S; Lavoie, Jean-Marc; Perez, Sérgio E. A.

    2016-01-01

    [Purpose] This study investigated the effects of ovariectomy (Ovx) and 12 weeks of resistance training (RT) on gene expression of GLUT2, the main glucose transporter in the liver, and on PPARγ, a transcription factor known to target GLUT2 expression. [Methods] Forty Holtzman rats were divided into 5 groups: Sham-sedentary (Sed), Sham- RT, Ovx-Sed, Ovx-RT, and Ovx-Sed with hormone replacement (E2). The RT protocol consisted of sessions held every 72 h for 12 weeks, during which the animals performed 4 to 9 vertical climbs (1.1 m) at 2 min intervals with progressively heavier weights (30 g after the fourth climb) tied to the tail. The E2 silastic capsule was inserted into the rats’ backs 48 hours before the first RT session. [Results] In addition to liver fat, GLUT2 protein levels and PPARγ transcripts were increased (P < 0.05) in Ovx compared to Sham-Sed animals, suggesting increased hepatic glucose uptake under estrogen deficient conditions. RT and E2 in Ovx rats decreased liver fat accumulation as well as GLUT2 and PPARγ gene expression to the level of Sham- Sed animals. [Conclusion] The results of this study suggest that liver GLUT2 as well as PPARγ expression in Ovx rats are accompanied by increased fat accumulation and glucose uptake, thus providing a substrate for increased de novo lipogenesis. RT appears to be an appropriate exercise model to circumvent these effects. PMID:27508154

  19. 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

  20. Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo *

    PubMed Central

    Wang, Jun-ming; Sheng, Yu-chen; Ji, Li-li; Wang, Zheng-tao

    2014-01-01

    The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B-induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity. PMID:24903991

  1. 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

  2. Increased MMP-7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia.

    PubMed

    Kerola, Anna; Lampela, Hanna; Lohi, Jouko; Heikkilä, Päivi; Mutanen, Annika; Hagström, Jaana; Tervahartiala, Taina; Sorsa, Timo; Haglund, Caj; Jalanko, Hannu; Pakarinen, Mikko P

    2016-07-01

    The molecular mechanisms underlying progressive liver fibrosis following surgical treatment of biliary atresia (BA) remain unclear. Our aim was to address hepatic gene and protein expression and serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after successful portoenterostomy (PE), and relate them to histological signs of liver injury, clinical follow-up data and biochemical markers of hepatic function. LIver biopsies and serum samples were obtained from 25 children after successful PE at median age of 3.3 years. Serum MMP concentrations were determined by enzyme-linked immune sorbent assay. Hepatic gene expression of MMPs and TIMPs was analyzed using real-time reverse-transcription PCR. Liver expression of MMP-7 and cytokeratin-7 was studied using immunohistochemistry. Despite effective clearance of biochemical and histological cholestasis following PE, BA patients showed increased hepatic gene expression of MMP-7 (29-fold, p < 0.001), MMP-2 (3.1-fold, p < 0.001), MMP-14 (1.7-fold, p = 0.007), and TIMP-1 (1.8-fold, p < 0.001), when compared to controls. Similar to a biliary epithelial marker cytokeratin-7, expression of MMP-7 localized in biliary epithelium of bile ducts and ductal proliferations and periportal hepatocytes and was increased (p < 0.001) in relation to controls. BA patients had 6-fold higher serum levels of MMP-7 (p < 0.001), which correlated positively with hepatic MMP-7 gene (r = 0.548, p = 0.007) and protein (r = 0.532, p = 0.007) expression. Patients showed a positive correlation between biliary MMP-7 expression and Metavir fibrosis stage (r = 0.605, p = 0.001) and portal fibrosis grade (r = 0.606, p = 0.001). Neither similarly increased MMP-7 expression nor correlation with liver fibrosis was observed in patients with intestinal failure-associated liver disease and comparable Metavir stage. In conclusion, our findings support an unique role of altered

  3. 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

  4. Genetics Home Reference: North American Indian childhood cirrhosis

    MedlinePlus

    ... Health Conditions North American Indian childhood cirrhosis North American Indian childhood cirrhosis Enable Javascript to view the expand/ ... Download PDF Open All Close All Description North American Indian childhood cirrhosis is a rare liver disorder that ...

  5. [Liver and artificial liver].

    PubMed

    Chamuleau, R A

    1998-06-01

    Despite good results of orthotopic liver transplantation in patients with fulminant hepatic failure the need still exists for an effective and safe artificial liver, able to temporarily take over the complex liver function so as to bridge the gap with transplantation or regeneration. Attempts to develop non-biological artificial livers have failed, mostly when controlled clinical trials were performed. In the last decade several different types of bioartificial livers have been devised, in which the biocomponent consists of freshly isolated porcine hepatocytes or a human hepatoblastoma cell line. The majority use semipermeable hollow fibers known from artificial kidney devices. The liver cells may lie either inside or outside the lumen of these fibers. In vitro analysis of liver function and animal experimental work showing that the bioartificial liver increases survival justify clinical application. Bioartificial livers are connected to patients extracorporeally by means of plasmapheresis circuit for periods of about 6 hours. In different trials about 40 patients with severe liver failure have been treated. No important adverse effects have not been reported in these phase I trials. Results of controlled studies are urgently needed. As long as no satisfactory immortalised human liver cell line with good function is available, porcine hepatocytes will remain the first choice, provided transmission of porcine pathogens to man is prevented. PMID:9752034

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

    PubMed Central

    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. PMID:27537547

  7. 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. PMID:24434909

  8. INCREASED LIVER PATHOLOGY IN HEPATITIS C VIRUS TRANSGENIC MICE EXPRESSING THE HEPATITIS B VIRUS X PROTEIN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 id...

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

    PubMed

    Cox, Andrew G; Hwang, Katie L; Brown, Kristin K; Evason, Kimberley J; 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

    2016-08-01

    The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signalling 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 tumour 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, suppressing 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

  10. 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. PMID:23861071

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

    PubMed Central

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

    2016-01-01

    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. PMID:26985891

  12. 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

  13. 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 a sample…

  14. 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

  15. 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

  16. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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. PMID:26472223

  2. 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. PMID:26101530

  3. 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". PMID:24275070

  4. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human

    PubMed Central

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-01-01

    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. PMID:27562371

  5. 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

    2016-01-01

    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. PMID:27562371

  6. 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…

  7. Increasing Awareness of Developmentally Appropriate Practices in the Early Childhood Education Community through Pre-Service and In-Service Training Programs.

    ERIC Educational Resources Information Center

    Crowther, Ingrid C.

    This practicum report describes a community college program developed for the purpose of increasing the awareness of early childhood personnel in a central Ontario (Canada) community concerning the benefits of developmentally appropriate practices. The need for the program arose from a discrepancy between the emphasis in community college courses…

  8. 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. PMID:26573906

  9. Increased long-latency reflex activity as a sufficient explanation for childhood hypertonic dystonia: a neuromorphic emulation study

    PubMed Central

    Sohn, Won J.; Niu, Chuanxin M.; Sanger, Terence D.

    2015-01-01

    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 long-latency stretch reflex leading to hypertonia. Approach We modelled 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 (VLSI) 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 32ms delay and a long-latency pathway with 64ms 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 long-latency stretch reflex is by itself sufficient to cause many of the features of hypertonic dystonia. PMID:25946372

  10. 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.

  11. Parental stress increases the effect of traffic-related air pollution on childhood asthma incidence

    PubMed Central

    Shankardass, Ketan; McConnell, Rob; Jerrett, Michael; Milam, Joel; Richardson, Jean; Berhane, Kiros

    2009-01-01

    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. PMID:19620729

  12. 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. PMID:20395947

  13. 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

  14. Increased Frequency of Micronuclei in Adults with a History of Childhood Sexual Abuse: A Discordant Monozygotic Twin Study

    PubMed Central

    York, Timothy P.; Brumelle, Jenni; Juusola, Jane; Kendler, Kenneth S.; Eaves, Lindon J.; Amstadter, Ananda B.; Aggen, Steven H.; Jones, Kimberly H.; Ferreira-Gonzalez, Andrea; Jackson-Cook, Colleen

    2013-01-01

    Background Childhood sexual abuse (CSA) is a traumatic life event associated with an increased lifetime risk for psychopathology/morbidity. The long-term biological consequences of CSA-elicited stress on chromosomal stability in adults are unknown. The primary aim of this study was to determine if the rate of acquired chromosomal changes, measured using the cytokinesis-block micronucleus assay on stimulated peripheral blood lymphocytes, differs in adult female monozygotic twins discordant for CSA. Methods Monozygotic twin pairs discordant for CSA were identified from a larger population-based sample of female adult twins for whom the experience of CSA was assessed by self-report (51 individuals including a reference sample). Micronuclei (MN) contain chromatin from structurally normal or abnormal chromosomes that are excluded from the daughter nuclei during cell division and serve as a biomarker to assess acquired chromosomal instability. Results Female twins exposed to CSA exhibited a 1.63-fold average increase in their frequency of MN compared to their nonexposed genetically identical cotwins (Paired t-test, t16 = 2.65, P = 0.017). No additional effects of familial factors were detected after controlling for the effect of CSA exposure. A significant interaction between CSA history and age was observed, suggesting that the biological effects of CSA on MN formation may be cumulative. Conclusions These data support a direct link between CSA exposure and MN formation measured in adults that is not attributable to genetic or environmental factors shared by siblings. Further research is warranted to understand the biological basis for the observed increase in acquired chromosomal findings in people exposed to CSA and to determine if acquired somatic chromosomal abnormalities/somatic clonal mosaicism might mediate the adult pathology associated with CSA. PMID:23383158

  15. Piceatannol increases the expression of hepatocyte growth factor and IL-10 thereby protecting hepatocytes in thioacetamide-induced liver fibrosis.

    PubMed

    Abd-Elgawad, Hazem; Abu-Elsaad, Nashwa; El-Karef, Amr; Ibrahim, Tarek

    2016-07-01

    Piceatannol is a polyphenolic analog of resveratrol that selectively inhibits the non-receptor tyrosine kinase-Syk. This study investigates the potential ability of piceatannol to attenuate liver fibrosis and protect hepatocytes from injury. Thioacetamide was injected in adult male mice (100 mg/kg, i.p., 3 times/week) for 8 weeks. Piceatannol (1 or 5 mg/kg per day) was administered by oral gavage during the last 4 weeks. Liver function biomarkers, tissue malondialdehyde (MDA), cytokeratin-18 (CK18), hepatocyte growth factor (HGF), and interleukin-10 (IL-10) were measured. Necroinflammation, fibrosis, expression of transforming growth factor (TGF)-β1, and α-smooth muscle actin (SMA) were scored by histopathological examination and immunohistochemistry. Obtained results showed ability of piceatannol (1 mg/kg) to restore liver function and reduce inflammation. It significantly (p < 0.001) reduced MDA, CK18, TGF-β1, and α-SMA expression, and increased HGF and IL-10. It can be concluded that piceatannol at low dose can inhibit TGF-β1 induced hepatocytes apoptosis and exerts an anti-inflammatory effect attenuating fibrosis progression. PMID:27186801

  16. 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. PMID:22461484

  17. 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

  18. 17β-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

    PubMed

    Mason, Julie K; Kharotia, Shikhil; Wiggins, Ashleigh K A; Kitson, Alex P; Chen, Jianmin; Bazinet, Richard P; Thompson, Lilian U

    2014-08-01

    Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status. PMID:24913495

  19. 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

  20. 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

  1. 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…

  2. Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation

    PubMed Central

    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

    2015-01-01

    Objectives: 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). Methods: 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. Results: (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. Conclusion: 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. PMID:26133108

  3. 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. PMID:26331987

  4. 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. PMID:25824762

  5. A Randomized Trial to Increase Acceptance of Childhood Vaccines by Vaccine-Hesitant Parents: A Pilot Study

    PubMed Central

    Williams, S. Elizabeth; Rothman, Russell L.; Offit, Paul A.; Schaffner, William; Sullivan, Molly; Edwards, Kathryn M.

    2013-01-01

    Objective A cluster-randomized trial was performed to evaluate an educational intervention to improve parental attitudes and vaccine uptake in vaccine-hesitant parents. Methods Two primary care sites were randomized to provide families with either usual care, or an intervention (video and written information) for vaccine-hesitant parents. Eligible parents included those presenting for their child’s 2 week well visit with performance on the Parent Attitudes about Childhood Vaccines (PACV) survey suggesting vaccine hesitancy (score ≥25). Enrollees completed PACV surveys at the 2 month well visit and vaccination status at 12 weeks of age was assessed. The primary outcome was the difference in PACV scores obtained at enrollment and 2 months between the two groups. The proportion of on-time vaccination was also compared at 12 weeks. Results 454 parents were approached and 369 (81.3%) participated; 132 had PACV scores ≥ 25 and were enrolled [67 in the control group (mean PACV score = 37) and 55 in the intervention group (mean PACV score = 40)]. Two month PACV surveys were completed by 108 (~90%) of enrollees. Parents in the intervention group had a significant decrease in PACV score at two months compared to control (median difference = 6.7, p=0.049); this remained significant after adjustment for baseline PACV score, race/ethnicity, and income (p=0.044). There was no difference in the on-time receipt of vaccines between groups at 12 weeks. Conclusions A brief educational intervention for vaccine-hesitant parents was associated with a modest but significant increase in measured parental attitudes towards vaccines. PMID:24011750

  6. Does autologous blood transfusion during liver transplantation for hepatocellular carcinoma increase risk of recurrence?

    PubMed Central

    Araujo, Raphael LC; Pantanali, Carlos Andrés; Haddad, Luciana; Rocha Filho, Joel Avancini; D’Albuquerque, Luiz Augusto Carneiro; Andraus, Wellington

    2016-01-01

    AIM: To analyze outcomes in patients who underwent liver transplantation (LT) for hepatocellular carcinoma (HCC) and received autologous intraoperative blood salvage (IBS). METHODS: Consecutive HCC patients who underwent LT were studied retrospectively and analyzed according to the use of IBS or not. Demographic and surgical data were collected from a departmental prospective maintained database. Statistical analyses were performed using the Fisher’s exact test and the Wilcoxon rank sum test to examine covariate differences between patients who underwent IBS and those who did not. Univariate and multivariate Cox regression models were developed to evaluate recurrence and death, and survival probabilities were estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: Between 2002 and 2012, 158 consecutive patients who underwent LT in the same medical center and by the same surgical team were identified. Among these patients, 122 (77.2%) were in the IBS group and 36 (22.8%) in the non-IBS group. The overall survival (OS) and recurrence free survival (RFS) at 5 years were 59.7% and 83.3%, respectively. No differences in OS (P = 0.51) or RFS (P = 0.953) were detected between the IBS and non-IBS groups. On multivariate analysis for OS, degree of tumor differentiation remained as the only independent predictor. Regarding patients who received IBS, no differences were detected in OS or RFS (P = 0.055 and P = 0.512, respectively) according to the volume infused, even when outcomes at 90 d or longer were analyzed separately (P = 0.518 for both outcomes). CONCLUSION: No differences in RFS or OS were detected according to IBS use. Trials addressing this question are justified and should be designed to detect small differences in long-term outcomes. PMID:26981190

  7. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. 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…

  9. 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…

  10. 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…

  11. Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography

    PubMed Central

    Harman, David J; Ryder, Stephen D; James, Martin W; Jelpke, Matthew; Ottey, Dominic S; Wilkes, Emilie A; Card, Timothy R; Aithal, Guruprasad P; Guha, Indra Neil

    2015-01-01

    Objectives To assess the feasibility of a novel diagnostic algorithm targeting patients with risk factors for chronic liver disease in a community setting. Design Prospective cross-sectional study. Setting Two primary care practices (adult patient population 10 479) in Nottingham, UK. Participants Adult patients (aged 18 years or over) fulfilling one or more selected risk factors for developing chronic liver disease: (1) hazardous alcohol use, (2) type 2 diabetes or (3) persistently elevated alanine aminotransferase (ALT) liver function enzyme with negative serology. Interventions A serial biomarker algorithm, using a simple blood-based marker (aspartate aminotransferase:ALT ratio for hazardous alcohol users, BARD score for other risk groups) and subsequently liver stiffness measurement using transient elastography (TE). Main outcome measures Diagnosis of clinically significant liver disease (defined as liver stiffness ≥8 kPa); definitive diagnosis of liver cirrhosis. Results We identified 920 patients with the defined risk factors of whom 504 patients agreed to undergo investigation. A normal blood biomarker was found in 62 patients (12.3%) who required no further investigation. Subsequently, 378 patients agreed to undergo TE, of whom 98 (26.8% of valid scans) had elevated liver stiffness. Importantly, 71/98 (72.4%) patients with elevated liver stiffness had normal liver enzymes and would be missed by traditional investigation algorithms. We identified 11 new patients with definite cirrhosis, representing a 140% increase in the number of diagnosed cases in this population. Conclusions A non-invasive liver investigation algorithm based in a community setting is feasible to implement. Targeting risk factors using a non-invasive biomarker approach identified a substantial number of patients with previously undetected cirrhosis. Trial registration number The diagnostic algorithm utilised for this study can be found on clinicaltrials.gov (NCT02037867), and is

  12. 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. PMID:26520617

  13. Combined dyslipidemia in childhood.

    PubMed

    Kavey, Rae-Ellen W

    2015-01-01

    Combined dyslipidemia (CD) is now the predominant dyslipidemic pattern in childhood, characterized by moderate-to-severe elevation in triglycerides and non-high-density lipoprotein cholesterol (non-HDL-C), minimal elevation in low-density lipoprotein cholesterol (LDL-C), and reduced HDL-C. Nuclear magnetic resonance spectroscopy shows that the CD pattern is represented at the lipid subpopulation level as an increase in small, dense LDL and in overall LDL particle number plus a reduction in total HDL-C and large HDL particles, a highly atherogenic pattern. In youth, CD occurs almost exclusively with obesity and is highly prevalent, seen in more than 40% of obese adolescents. CD in childhood predicts pathologic evidence of atherosclerosis and vascular dysfunction in adolescence and young adulthood, and early clinical cardiovascular events in adult life. There is a tight connection between CD, visceral adiposity, insulin resistance, nonalcoholic fatty liver disease, and the metabolic syndrome, suggesting an integrated pathophysiological response to excessive weight gain. Weight loss, changes in dietary composition, and increases in physical activity have all been shown to improve CD significantly in children and adolescents in short-term studies. Most importantly, even small amounts of weight loss are associated with significant decreases in triglyceride levels and increases in HDL-C levels with improvement in lipid subpopulations. Diet change focused on limitation of simple carbohydrate intake with specific elimination of all sugar-sweetened beverages is very effective. Evidence-based recommendations for initiating diet and activity change are provided. Rarely, drug therapy is needed, and the evidence for drug treatment of CD in childhood is reviewed. PMID:26343211

  14. High-sucrose diet increases ROS generation, FFA accumulation, UCP2 level, and proton leak in liver mitochondria.

    PubMed

    Ruiz-Ramírez, Angélica; Chávez-Salgado, Monserrath; Peñeda-Flores, José Antonio; Zapata, Estrella; Masso, Felipe; El-Hafidi, Mohammed

    2011-12-01

    Obesity, a risk factor for insulin resistance, contributes to the development of type 2 diabetes and cardiovascular diseases. The relationship between increased levels of free fatty acids in the liver mitochondria, mitochondrial function, and ROS generation in rat model of obesity induced by a high-sucrose diet was not sufficiently established. We determined how the bioenergetic functions and ROS generation of the mitochondria respond to a hyperlipidemic environment. Mitochondria from sucrose-fed rats generated H(2)O(2) at a higher rate than the control mitochondria. Adding fatty acid-free bovine serum albumin to mitochondria from sucrose-fed rats significantly reduced the rate of H(2)O(2) generation. In contrast, adding exogenous oleic or linoleic acid exacerbated the rate of H(2)O(2) generation in both sucrose-fed and control mitochondria, and the mitochondria from sucrose-fed rats were more sensitive than the control mitochondria. The increased rate of H(2)O(2) generation in sucrose-fed mitochondria corresponded to decreased levels of reduced GSH and vitamin E and increased levels of Cu/Zn-SOD in the intermembrane space. There was no difference between the levels of lipid peroxidation and protein carbonylation in the two types of mitochondria. In addition to the normal activity of Mn-SOD, GPX and catalase detected an increased activity of complex II, and upregulation of UCP2 was observed in mitochondria from sucrose-fed rats, all of which may accelerate respiration rates and reduce generation of ROS. In turn, these effects may protect the mitochondria of sucrose-fed rats from oxidative stress and preserve their function and integrity. However, in whole liver these adaptive mechanisms of the mitochondria were inefficient at counteracting redox imbalances and inhibiting oxidative stress outside of the mitochondria. PMID:21917631

  15. 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.

  16. 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

    2014-01-01

    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. PMID:25299819

  17. Sugars increase non-heme iron bioavailability in human epithelial intestinal and liver cells.

    PubMed

    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

  18. Suppressed liver tumorigenesis in fat-1 mice with elevated omega-3 fatty acids is associated with increased omega-3 derived lipid mediators and reduced TNF-α

    PubMed Central

    Weylandt, Karsten H.; Krause, Lena F.; Gomolka, Beate; Chiu, Cheng-Ying; Bilal, Süleyman; Nadolny, Anja; Waechter, Simon F.; Fischer, Andreas; Rothe, Michael

    2011-01-01

    Liver tumors, particularly hepatocellular carcinoma (HCC), are a major cause of morbidity and mortality worldwide. The development of HCC is mostly associated with chronic inflammatory liver disease of various etiologies. Previous studies have shown that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) dampen inflammation in the liver and decrease formation of tumor necrosis factor (TNF)-α. In this study, we used the fat-1 transgenic mouse model, which endogenously forms n-3 PUFA from n-6 PUFA to determine the effect of an increased n-3 PUFA tissue status on tumor formation in the diethylnitrosamine (DEN)-induced liver tumor model. Our results showed a decrease in tumor formation, in terms of size and number, in fat-1 mice compared with wild-type littermates. Plasma TNF-α levels and liver cyclooxygenase-2 expression were markedly lower in fat-1 mice. Furthermore, there was a decreased fibrotic activity in the livers of fat-1 mice. Lipidomics analyses of lipid mediators revealed significantly increased levels of the n-3 PUFA-derived 18-hydroxyeicosapentaenoic acid (18-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDHA) in the livers of fat-1 animals treated with DEN. In vitro experiments showed that 18-HEPE and 17-HDHA could effectively suppress lipopolysacharide-triggered TNF-α formation in a murine macrophage cell line. The results of this study provide evidence that an increased tissue status of n-3 PUFA suppresses liver tumorigenesis, probably through inhibiting liver inflammation. The findings also point to a potential anticancer role for the n-3 PUFA-derived lipid mediators 18-HEPE and 17-HDHA, which can downregulate the important proinflammatory and proproliferative factor TNF-α. PMID:21421544

  19. 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

  20. Resilience to childhood maltreatment is associated with increased resting-state functional connectivity of the salience network with the lingual gyrus.

    PubMed

    van der Werff, Steven J A; Pannekoek, J Nienke; Veer, Ilya M; van Tol, Marie-José; Aleman, André; Veltman, Dick J; Zitman, Frans G; Rombouts, Serge A R B; Elzinga, Bernet M; van der Wee, Nic J A

    2013-11-01

    The experience of childhood maltreatment is related to an increased risk of developing a variety of psychiatric disorders, as well as a change in the structure of the brain. However, not much is known about the neurobiological basis of resilience to childhood maltreatment. This study aims to identify resting-state functional connectivity (RSFC) patterns specific for resilience to childhood maltreatment, focusing on the default mode and salience network and networks seeded from the amygdala and left dorsomedial prefrontal cortex. Resting-state functional MRI scans were obtained in 33 individuals. Seeds in the bilateral amygdala, the dorsal anterior cingulate cortex (dACC), the posterior cingulate cortex and the left dorsomedial prefrontal cortex were defined and used to examine whether resilient individuals differed from vulnerable individuals and healthy controls in RSFC with other brain regions. Within the salience network, the resilient group was associated with increased RSFC between the left dACC and a region containing the bilateral lingual gyrus and the occipital fusiform gyrus compared to both the vulnerable group and the healthy controls. In this study, we found RSFC patterns specific for resilient individuals. Regions that are implicated are related on a functional level to declarative memory and the processing of emotional stimuli. PMID:23948312

  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. PMID:27430420

  2. Increased expression of 78 kD glucose-regulated protein promotes cardiomyocyte apoptosis in a rat model of liver cirrhosis

    PubMed Central

    Zhang, Lili; Zhang, Huiying; Lv, Minli; Jia, Jiantao; Fan, Yimin; Tian, Xiaoxia; Li, Xujiong; Li, Baohong; Ji, Jingquan; Wang, Limin; Zhao, Zhongfu; Han, Dewu; Ji, Cheng

    2015-01-01

    Aims: This study was to investigate the role and underlying mechanism of 78 kD glucose-regulated protein (GRP78) in cardiomyocyte apoptosis in a rat model of liver cirrhosis. Methods: A rat model of liver cirrhosis was established with multiple pathogenic factors. A total of 42 male SD rats were randomly divided into the liver cirrhosis group and control group. Cardiac structure analysis was performed to assess alterations in cardiac structure. Cardiomyocytes apoptosis was detected by TdT-mediated dUTP nick end labeling method. Expression of GRP78, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) and B cell lymphoma-2 (Bcl-2) was detected by immunohistochemical staining. Results: The ratios of left ventricular wall thickness to heart weight and heart weight to body weight were significantly increased with the progression of liver cirrhosis (P < 0.05). Apoptosis index of cardiomyocytes was significantly increased with the progression of liver cirrhosis (P < 0.05). The expression levels of GRP78, CHOP and caspase-12 were significantly increased in the progression of liver cirrhosis (P < 0.05). The expression levels of NF-κB p65 and Bcl-2 were highest in the 4-wk liver cirrhosis, and they were decreased in the 6-wk and 8-wk in the progression of liver cirrhosis. GRP78 expression levels were positively correlated with apoptosis index, CHOP and caspase-12 expression levels (P < 0.05). CHOP expression levels were negatively correlated with NF-κB p65 and Bcl-2 expression levels (P < 0.05). Conclusion: Increased expression of GRP78 promotes cardiomyocyte apoptosis in rats with cirrhotic cardiomyopathy. PMID:26464674

  3. Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia-reperfusion injury in steatotic livers of ob/ob mice

    PubMed Central

    Hasegawa, Tadashi; Ito, Yoshiya; Wijeweera, Jayanthika; Liu, Jie; Malle, Ernst; Farhood, Anwar; McCuskey, Robert S.; Jaeschke, Hartmut

    2016-01-01

    Steatosis is a major risk factor for complications after liver surgery. Since neutrophil cytotoxicity is critical for ischemia-reperfusion injury in normal livers, the aim of the present study was to evaluate whether an exaggerated inflammatory response could cause the increased injury in steatotic livers. In C57Bl/6 mice, 60 min of warm hepatic ischemia triggered a gradual increase in hepatic neutrophil accumulation during reperfusion with peak levels of 100-fold over baseline at 12 h of reperfusion. Neutrophil extravasation and a specific neutrophil-induced oxidant stress (immunostaining for hypochlorous acid-modified epitopes) started at 6 h of reperfusion and peaked at 12–24 h. Ob/ob mice, which had a severe macrovesicular steatosis, suffered significantly higher injury (alanine transaminase activity: 18,000 ± 2,100 U/l; 65% necrosis) compared with lean littermates (alanine transaminase activity: 4,900 ± 720 U/l; 24% necrosis) at 6 h of reperfusion. However, 62% fewer neutrophils accumulated in steatotic livers. This correlated with an attenuated increase in mRNA levels of several proinflammatory genes in ob/ob mice during reperfusion. In contrast, sham-operated ob/ob mice had a 50% reduction in liver blood flow and 35% fewer functional sinusoids compared with lean littermates. These deficiencies in liver blood flow and the microcirculation were further aggravated only in ob/ob mice during reperfusion. The attenuated inflammatory response and reduced neutrophil-induced oxidant stress observed in steatotic livers during reperfusion cannot be responsible for the dramatically increased injury in ob/ob mice. In contrast, the aggravated injury appears to be mediated by ischemic necrosis due to massive impairment of blood and oxygen supply in the steatotic livers. PMID:17307725

  4. Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia-reperfusion injury in steatotic livers of ob/ob mice.

    PubMed

    Hasegawa, Tadashi; Ito, Yoshiya; Wijeweera, Jayanthika; Liu, Jie; Malle, Ernst; Farhood, Anwar; McCuskey, Robert S; Jaeschke, Hartmut

    2007-05-01

    Steatosis is a major risk factor for complications after liver surgery. Since neutrophil cytotoxicity is critical for ischemia-reperfusion injury in normal livers, the aim of the present study was to evaluate whether an exaggerated inflammatory response could cause the increased injury in steatotic livers. In C57Bl/6 mice, 60 min of warm hepatic ischemia triggered a gradual increase in hepatic neutrophil accumulation during reperfusion with peak levels of 100-fold over baseline at 12 h of reperfusion. Neutrophil extravasation and a specific neutrophil-induced oxidant stress (immunostaining for hypochlorous acid-modified epitopes) started at 6 h of reperfusion and peaked at 12-24 h. Ob/ob mice, which had a severe macrovesicular steatosis, suffered significantly higher injury (alanine transaminase activity: 18,000 +/- 2,100 U/l; 65% necrosis) compared with lean littermates (alanine transaminase activity: 4,900 +/- 720 U/l; 24% necrosis) at 6 h of reperfusion. However, 62% fewer neutrophils accumulated in steatotic livers. This correlated with an attenuated increase in mRNA levels of several proinflammatory genes in ob/ob mice during reperfusion. In contrast, sham-operated ob/ob mice had a 50% reduction in liver blood flow and 35% fewer functional sinusoids compared with lean littermates. These deficiencies in liver blood flow and the microcirculation were further aggravated only in ob/ob mice during reperfusion. The attenuated inflammatory response and reduced neutrophil-induced oxidant stress observed in steatotic livers during reperfusion cannot be responsible for the dramatically increased injury in ob/ob mice. In contrast, the aggravated injury appears to be mediated by ischemic necrosis due to massive impairment of blood and oxygen supply in the steatotic livers. PMID:17307725

  5. Resveratrol Induces a Mitochondrial Complex I-dependent Increase in NADH Oxidation Responsible for Sirtuin Activation in Liver Cells*

    PubMed Central

    Desquiret-Dumas, Valérie; Gueguen, Naïg; Leman, Géraldine; Baron, Stéphanie; Nivet-Antoine, Valérie; Chupin, Stéphanie; Chevrollier, Arnaud; Vessières, Emilie; Ayer, Audrey; Ferré, Marc; Bonneau, Dominique; Henrion, Daniel; Reynier, Pascal; Procaccio, Vincent

    2013-01-01

    Resveratrol (RSV) has been shown to be involved in the regulation of energetic metabolism, generating increasing interest in therapeutic use. SIRT1 has been described as the main target of RSV. However, recent reports have challenged the hypothesis of its direct activation by RSV, and the signaling pathways remain elusive. Here, the effects of RSV on mitochondrial metabolism are detailed both in vivo and in vitro using murine and cellular models and isolated enzymes. We demonstrate that low RSV doses (1–5 μm) directly stimulate NADH dehydrogenases and, more specifically, mitochondrial complex I activity (EC50 ∼1 μm). In HepG2 cells, this complex I activation increases the mitochondrial NAD+/NADH ratio. This higher NAD+ level initiates a SIRT3-dependent increase in the mitochondrial substrate supply pathways (i.e. the tricarboxylic acid cycle and fatty acid oxidation). This effect is also seen in liver mitochondria of RSV-fed animals (50 mg/kg/day). We conclude that the increase in NADH oxidation by complex I is a crucial event for SIRT3 activation by RSV. Our results open up new perspectives in the understanding of the RSV signaling pathway and highlight the critical importance of RSV doses used for future clinical trials. PMID:24178296

  6. 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.

  7. Atorvastatin increases miR-124a expression: a mechanism of Gamt modulation in liver cells.

    PubMed

    Phulukdaree, Alisa; Moodley, Devapregasan; Khan, Sajidah; Chuturgoon, Anil A

    2015-11-01

    Atorvastatin is used to control cholesterol and lipid levels in hyperlipidaemic and hypercholesterolaemic patients. Myopathy and hepatotoxicity, however, have been reported as side effects in a small percentage of statin users. This study aimed to investigate the cytotoxicity and the effect of atorvastatin on microRNA expression in HepG2 cells. The methylthiazol tetrazolium assay was used to assess hepatocyte viability and at 20 μM atorvastatin (24 h) treatment were 82 ± 1.5% viable (P = 0.0002). Levels of intracellular ATP in cells treated with 20 μM atorvastatin were reduced by 1.25-fold, P = 0.002. Cytotoxicity, measured by the release of intracellular lactate dehydrogenase, was increased from 0.95 ± 0.29 units in control cells to 1.12 ± 0.02 units (P = 0.002) in atorvastatin treated cells. A panel of 84-miRNA species was used to evaluate the effect of atorvastatin on miRNA expression. MiR-124a was significantly up-regulated by atorvastatin (12.94-fold). A significant decrease in GAMT expression (3.54-fold) was observed in atorvastatin treated cells following quantitative PCR analysis. In addition, western blotting data showed GAMT protein levels were significantly lower than the controls (3.02-fold) and analysis of creatine levels in treated cells showed a significant decrease in the atorvastatin treated culture supernatant compared to control culture supernatant (32.33 ± 3.51 μM/l vs. 59.67 ± 1.52μM/l, P = 0.0056). This is the first study to show that atorvastatin up-regulates miR-124a levels and consequently modulates GAMT expression in hepatocytes. PMID:25926069

  8. 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. PMID:27086005

  9. Elevation in liver enzymes is associated with increased IL-2 and predicts severe outcomes in clinically apparent dengue virus infection.

    PubMed

    Senaratne, Thamarasi; Carr, Jillian; Noordeen, Faseeha

    2016-07-01

    The objective of the present study was to assess the circulating TNF-α and IL-2 levels in dengue virus (DENV) infected patients and to correlate these with clinical severity of DENV infections. A single analyte quantitative immunoassay was used to detect TNF-α and IL-2 in 24 dengue fever (DF) and 43 dengue haemorrhagic fever (DHF) patients, 15 healthy adults and 6 typhoid patients. The mean TNF-α and IL-2 levels of DENV- infected patients were higher than that of healthy adults and typhoid patients. No significant difference in TNF-α levels was noted between DF and DHF patients (p=0.5) but a significant increase in IL-2 levels was observed in DHF compared with DF patients (mean of DF=59.7pg/mL, mean of DHF=166.9pg/mL; p=0.02). No significant association of TNF-α or IL-2 levels was noted with packed cell volume (>45), thrombocytopenia, leucopenia or the presence of viraemia. The liver function tests measuring AST (aspartate aminotransferase) (p=0.01) and ALT (alanine aminotransferase) (p=0.02) levels were significantly elevated in DENV-infected patients. AST:ALT was significantly elevated in DHF/DSS (dengue shock syndrome) compared with DF patients. A significant positive linear correlation was noted between AST and IL-2 (r=0.31; p=0.01) and ALT and IL-2 elevations (r=0.2; p=0.02). Thus, AST and ALT levels correlate with both disease severity and circulating IL-2 levels. We suggest a role for circulating IL-2 in liver dysfunction and propose that a combined assessment of AST/ALT in conjunction with IL-2 at the early stages of symptomatic DENV infection may be useful to predict the severe forms of dengue. PMID:27155816

  10. 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

  11. Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis B

    PubMed Central

    Tang, Kuo-Tung; Hung, Wei-Ting; Chen, Yi-Hsing; Lin, Ching-Heng; Chen, Der-Yuan

    2016-01-01

    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. PMID:26928373

  12. 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

  13. 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

    2016-01-01

    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. PMID:26928373

  14. Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis C.

    PubMed

    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

  15. Analyzing the impact of increasing Mechanical Index (MI) and energy deposition on shear wave speed (SWS) reconstruction in human liver

    PubMed Central

    Deng, Yufeng; Palmeri, Mark L.; Rouze, Ned C.; Rosenzweig, Stephen J.; Abdelmalek, Manal F.; Nightingale, Kathryn R.

    2015-01-01

    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 2 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 8 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. PMID:25896024

  16. 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

  17. 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.

  18. Testosterone Increases Susceptibility to Amebic Liver Abscess in Mice and Mediates Inhibition of IFNγ Secretion in Natural Killer T Cells

    PubMed Central

    Lotter, Hannelore; Helk, Elena; Bernin, Hannah; Jacobs, Thomas; Prehn, Cornelia; Adamski, Jerzy; González-Roldán, Nestor; Holst, Otto; Tannich, Egbert

    2013-01-01

    Amebic liver abscess (ALA), a parasitic disease due to infection with the protozoan Entamoeba histolytica, occurs age and gender dependent with strong preferences for adult males. Using a mouse model for ALA with a similar male bias for the disease, we have investigated the role of female and male sexual hormones and provide evidence for a strong contribution of testosterone. Removal of testosterone by orchiectomy significantly reduced sizes of abscesses in male mice, while substitution of testosterone increased development of ALA in female mice. Activation of natural killer T (NKT) cells, which are known to be important for the control of ALA, is influenced by testosterone. Specifically activated NKT cells isolated from female mice produce more IFNγ compared to NKT cells derived from male mice. This high level production of IFNγ in female derived NKT cells was inhibited by testosterone substitution, while the IFNγ production in male derived NKT cells was increased by orchiectomy. Gender dependent differences were not a result of differences in the total number of NKT cells, but a result of a higher activation potential for the CD4− NKT cell subpopulation in female mice. Taken together, we conclude that the hormone status of the host, in particular the testosterone level, determines susceptibility to ALA at least in a mouse model of the disease. PMID:23424637

  19. Testosterone increases susceptibility to amebic liver abscess in mice and mediates inhibition of IFNγ secretion in natural killer T cells.

    PubMed

    Lotter, Hannelore; Helk, Elena; Bernin, Hannah; Jacobs, Thomas; Prehn, Cornelia; Adamski, Jerzy; González-Roldán, Nestor; Holst, Otto; Tannich, Egbert

    2013-01-01

    Amebic liver abscess (ALA), a parasitic disease due to infection with the protozoan Entamoeba histolytica, occurs age and gender dependent with strong preferences for adult males. Using a mouse model for ALA with a similar male bias for the disease, we have investigated the role of female and male sexual hormones and provide evidence for a strong contribution of testosterone. Removal of testosterone by orchiectomy significantly reduced sizes of abscesses in male mice, while substitution of testosterone increased development of ALA in female mice. Activation of natural killer T (NKT) cells, which are known to be important for the control of ALA, is influenced by testosterone. Specifically activated NKT cells isolated from female mice produce more IFNγ compared to NKT cells derived from male mice. This high level production of IFNγ in female derived NKT cells was inhibited by testosterone substitution, while the IFNγ production in male derived NKT cells was increased by orchiectomy. Gender dependent differences were not a result of differences in the total number of NKT cells, but a result of a higher activation potential for the CD4(-) NKT cell subpopulation in female mice. Taken together, we conclude that the hormone status of the host, in particular the testosterone level, determines susceptibility to ALA at least in a mouse model of the disease. PMID:23424637

  20. 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

  1. 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

    2015-01-01

    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

  2. Childhood Obesity

    PubMed Central

    Ahmad, Qazi Iqbal; Ahmad, Charoo Bashir; Ahmad, Sheikh Mushtaq

    2010-01-01

    Obesity is increasing at an alarming rate throughout the world. Today it is estimated that there are more than 300 million obese people world-wide. Obesity is a condition of excess body fat often associated with a large number of debilitating and life-threatening disorders. It is still a matter of debate as to how to define obesity in young people. Overweight children have an increased risk of being overweight as adults. Genetics, behavior, and family environment play a role in childhood overweight. Childhood overweight increases the risk for certain medical and psychological conditions. Encourage overweight children to expand high energy activity, minimize low energy activity (screen watching), and develop healthful eating habits. Breast feeding is protective against obesity. Diet restriction is not recommended in very young children. Children are to be watched for gain in height rather than reduction in weight. Weight reduction of less than 10% is a normal variation, not significant in obesity. PMID:21448410

  3. Childhood obesity.

    PubMed

    Ahmad, Qazi Iqbal; Ahmad, Charoo Bashir; Ahmad, Sheikh Mushtaq

    2010-01-01

    Obesity is increasing at an alarming rate throughout the world. Today it is estimated that there are more than 300 million obese people world-wide. Obesity is a condition of excess body fat often associated with a large number of debilitating and life-threatening disorders. It is still a matter of debate as to how to define obesity in young people. Overweight children have an increased risk of being overweight as adults. Genetics, behavior, and family environment play a role in childhood overweight. Childhood overweight increases the risk for certain medical and psychological conditions. Encourage overweight children to expand high energy activity, minimize low energy activity (screen watching), and develop healthful eating habits. Breast feeding is protective against obesity. Diet restriction is not recommended in very young children. Children are to be watched for gain in height rather than reduction in weight. Weight reduction of less than 10% is a normal variation, not significant in obesity. PMID:21448410

  4. Stages of Childhood Liver Cancer

    MedlinePlus

    ... checked for pieces of the hepatitis virus . MRI (magnetic resonance imaging) with gadolinium : A procedure that uses a magnet, ... the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI). Enlarge Magnetic resonance imaging (MRI) of the ...

  5. Is there an increased risk of metabolic syndrome among childhood acute lymphoblastic leukemia survivors? A developing country experience.

    PubMed

    Mohapatra, Sonali; Bansal, Deepak; Bhalla, A K; Verma Attri, Savita; Sachdeva, Naresh; Trehan, Amita; Marwaha, R K

    2016-03-01

    Data on metabolic syndrome (MS) in survivors of childhood acute lymphoblastic leukemia (ALL) from developing countries are lacking. The purpose of this single-center, uncontrolled, observational study was to assess the frequency of MS in our survivors. The survivors of ALL ≤15 years at diagnosis, who had completed therapy ≥2 years earlier, were enrolled. Anthropometric measurements (weight, height, waist circumference), biochemistry (glucose, insulin, triglycerides, high-density lipoprotein [HDL], thyroid function tests, C-reactive protein [CRP], magnesium), measurement of blood pressure, and Tanner staging were performed. MS was defined by International Diabetes Federation (IDF) and the National Cholesterol Education Program Third Adult Treatment Panel guidelines (NCEP ATP III) criteria, modified by Cook et al. (Arch Pediatr Adolesc Med. 2003;157:821-827) and Ford et al. (Diabetes Care. 2005;28:878-881). The median age of 76 survivors was 11.9 years (interquartile range [IQR]: 9.6-13.5). Twenty-four (32%) survivors were obese or overweight. The prevalence of insulin resistance (17%), hypertension (7%), hypertriglyceridemia (20%), and low HDL (37%) was comparable to the prevalence in children/adolescents in historical population-based studies from India. The prevalence of MS ranged from 1.3% to 5.2%, as per different defining criteria. Cranial radiotherapy, age at diagnosis, sex, or socioeconomic status were not risk factors for MS. The prevalence of MS in survivors of childhood ALL, at a median duration of 3 years from completion of chemotherapy, was comparable to the reference population. The prevalence of being obese or overweight was, however, greater than historical controls. PMID:26984439

  6. 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

  7. 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. PMID:27185751

  8. Liver growth factor induces testicular regeneration in EDS-treated rats and increases protein levels of class B scavenger receptors.

    PubMed

    Lobo, M V T; Arenas, M I; Huerta, L; Sacristán, S; Pérez-Crespo, M; Gutiérrez-Adán, A; Díaz-Gil, J J; Lasunción, M A; Martín-Hidalgo, A

    2015-01-15

    The aim of the present work was to determine the effects of liver growth factor (LGF) on the regeneration process of rat testes after chemical castration induced by ethane dimethanesulfonate (EDS) by analyzing some of the most relevant proteins involved in cholesterol metabolism, such as hormone sensitive lipase (HSL), 3β-hydroxysteroid dehydrogenase (3β-HSD), scavenger receptor SR-BI, and other components of the SR family that could contribute to the recovery of steroidogenesis and spermatogenesis in the testis. Sixty male rats were randomized to nontreated (controls) and LGF-treated, EDS-treated, and EDS + LGF-treated groups. Testes were obtained on days 10 (T1), 21 (T2), and 35 (T3) after EDS treatment, embedded in paraffin, and analyzed by immunohistochemistry and Western blot. LGF improved the recovery of the seminiferous epithelia, the appearance of the mature pattern of Leydig cell interstitial distribution, and the expression of mature SR-BI. Moreover, LGF treatment resulted in partial recovery of HSL expression in Leydig cells and spermatogonia. No changes in serum testosterone were observed in control or LGF-treated rats, but in EDS-castrated animals LGF treatment induced a progressive increase in serum testosterone levels and 3β-HSD expression. Based on the pivotal role of SR-BI in the uptake of cholesteryl esters from HDL, it is suggested that the observed effects of LGF would facilitate the provision of cholesterol for sperm cell growth and Leydig cell recovery. PMID:25389365

  9. [The flavonoids effect against vinblastine, cyclophosphamide and paracetamol toxicity by inhibition of lipid-peroxydation and increasing liver glutathione concentration].

    PubMed

    Lahouel, M; Boulkour, S; Segueni, N; Fillastre, J P

    2004-07-01

    The paracetamol and cyclophosphamid are metabolized in the liver by the cytochrome P450. The formed reactive intermediates are responsible of a hepatocyte depletion of the glutathion and a lipoperoxydation. the vinblastine is also a chemotherapeutic agent hepatotoxic and hematotoxic. Otherwise, flavonoïds are polyphenols substances of plant origin having some biological and anti-oxydative properties. However no information is available on their effects on glutathion and glutathion-s-transferases. In our research, we valued the effect of oral administration of flavonoids (diosmine and quercetine) under shape of propolis extract to 60 mg/kg daily during 14 days, on hematological and hepatic toxicity of a single dose of cyclophosphamide 80 mg/kg by intravenous way, vinblastine 2 mg/kg by intravenous way and the hepatic toxicity of the paracetamol managed by oral way to 200 mg/kg corresponding to 2/3 the DL50 at the rat female albinos wistar. We did a blood numeration, an assessment of serum activities of transaminases and alkali phosphatases as well as quantification of the glutathion and the malondialdehyde (MDA) in liver homogenats of rats treated. Analyses are done at regular intervals; 1, 3, 7 and 14 days after the administration of drugs. In the group of rats treated by the cyclophosphamid paracetamol alone we observed since the 1st day, an increase of lipid peroxide (MDA) of 120% and a downfall of hepatic glutathion including the group receiving the vinblastine (until 210% of reduction). In the same way a severe leucopenia and a thrombopenia (70% of reduction) are observed between the 3rd and the 14th day at rats treated by the chemotherapeutic agents alone (cyclophosphamide and vinblastine). The combination of flavonoids with drugs have clearly reduced the effect of drugs toxicity. Indeed, the aplasic observed with the vinblastine, as well as the leucopenia and thrombopenia of the cyclophosphamide are corrected entirely. In the same way, we noted a restoration

  10. Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome

    PubMed Central

    Pereira, Troy J; Fonseca, Mario A; Campbell, Kristyn E; Moyce, Brittany L; Cole, Laura K; Hatch, Grant M; Doucette, Christine A; Klein, Julianne; Aliani, Michel; Dolinsky, Vernon W

    2015-01-01

    Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring. Key points Gestational diabetes mellitus is a common complication of pregnancy, but its effects on the offspring are poorly understood. We developed a rat model of diet-induced gestational diabetes mellitus that recapitulates many of the clinical features of the disease, including excessive gestational

  11. Short term exposure to perluoroalkyl acids causes increase of hepatic lipid and triglyceride in conjunction with liver hypertrophy

    EPA Science Inventory

    ABSTRACT BODY: Persistent presence of perfluoroalkyl acids (PFAAs) in the environment is due to extensive use of industrial and consumer products. These chemicals activate peroxisome proliferatoractivated receptor-alpha (PPARa) in liver and after lipid metabolism. The current stu...

  12. High feeding intensity increases the severity of fatty liver in the American mink (Neovison vison) with potential ameliorating role for long-chain n-3 polyunsaturated fatty acids

    PubMed Central

    2014-01-01

    Background Rapid body fat mobilization, obesity, and an inadequate supply of n-3 polyunsaturated fatty acids (PUFA) have been suggested to play roles in the etiology of fatty liver in the American mink (Neovison vison). This study examined the effects of feeding intensity and dietary fat source on fatty liver induced by fasting. In a multi-factorial design, 3 different fat sources (herring oil, rich in n-3 PUFA, soya oil, rich in n-6 PUFA, and canola oil, rich in n-9 monounsaturated fatty acids) were fed to mink at a low and high feeding intensity for 10 weeks, followed by an overnight or a 5-day fasting treatment to induce fatty liver. Results Fasting led to the development of fatty liver with increased severity in the mink fed at the high feeding intensity. The herring oil diet, high in long-chain n-3 PUFA, was found to decrease the severity of fatty liver in the mink at the high feeding intensity. Conclusion Preventing excessive weight gain and increasing dietary intake of n-3 long-chain PUFA may help prevent excessive lipid accumulation during prolonged periods of fasting or inappetence by promoting hepatic fatty acid oxidation. PMID:24438337

  13. Interleukin-10 increases reverse cholesterol transport in macrophages through its bidirectional interaction with liver X receptor α

    SciTech Connect

    Halvorsen, Bente; Holm, Sverre; Yndestad, Arne; Scholz, Hanne; Sagen, Ellen Lund; Nebb, Hilde; Holven, Kirsten B.; Dahl, Tuva B.; Aukrust, Pål

    2014-08-08

    Highlights: • IL-10 promotes reverse cholesterol efflux from lipid loaded macrophages. • IL-10 increases the expression of ABCA-1 and ABCG-1. • IL-10 exhibits cross-talk with the nuclear receptor LXRα. - Abstract: Interleukin (IL)-10 is a prototypical anti-inflammatory cytokine that has been shown to attenuate atherosclerosis development. In addition to its anti-inflammatory properties, the anti-atherogenic effect of IL-10 has recently also been suggested to reflect a complex effect of IL-10 on lipid metabolism in macrophages. In the present study we examined the effects of IL-10 on cholesterol efflux mechanism in lipid-loaded THP-1 macrophages. Our main findings were: (i) IL-10 significantly enhanced cholesterol efflux induced by fetal-calf serum, high-density lipoprotein (HDL){sub 2} and apolipoprotein A-1. (ii) The IL-10-mediated effects on cholesterol efflux were accompanied by an increased IL-10-mediated expression of the ATP-binding cassette transporters ABCA1 and ABCG1, that was further enhanced when the cells were co-activated with the liver X receptor (LXR)α agonist (22R)-hydroxycholesterol. (iii) The effect of LXRα activation on the IL-10-mediated effects on the ATP-binding cassette transporters seems to include enhancing effects on the IL-10 receptor 1 (IL10R1) expression and interaction with STAT-3 signaling. (iv) These enhancing effects on ABCA1 and ABCG1 was not seen when the cells were stimulated with the IL-10 family members IL-22 and IL-24. This study suggests that the anti-atherogenic properties of IL-10 may include enhancing effects on cholesterol efflux mechanism that involves cross-talk with LXRα activation.

  14. Increasing expression of gastrointestinal phenotypes and p53 along with histologic progression of intraductal papillary neoplasia of the liver.

    PubMed

    Shimonishi, Tomonori; Zen, Yoh; Chen, Tse-Ching; Chen, Miin-Fu; Jan, Yi-Yin; Yeh, Ta-Sen; Nimura, Yuji; Nakanuma, Yasuni

    2002-05-01

    Intraductal papillary neoplasia of the liver (IPN-L) was recently proposed as the name for intraductal papillary proliferation of neoplastic biliary epithelium with a fine fibrovascular stalk resembling intraductal papillary mucinous neoplasm of the pancreas. We histochemically and immunohistochemically examined IPN-L alone or associated with hepatolithiasis, with an emphasis on the gastrointestinal metaplasia, nuclear p53 expression, and histologic progression. A total of 66 cases of IPN-L were divided into 4 groups: group 1, IPN-L with low-grade dysplasia (13 cases); group 2, IPN-L with high-grade dysplasia (20 cases); group 3, IPN-L lined with carcinoma in situ and no or microinvasion (19 cases); and group 4, group 3 with distinct invasive carcinoma (14 cases). It is suggested that IPN-L progresses from group 1 to group 4. As controls, 20 cases of nonneoplastic intrahepatic large bile ducts and 17 cases of nonpapillary invasive intrahepatic cholangiocarcinoma (ICC) were used. Biliary epithelial hypersecretion of sialomucin rather than sulfomucin was prevalent in IPN-L, and this was associated with the progression of INP-L. Immunohistochemically, cytokeratin (CK) 20 and MUC2, a gastrointestinal marker, were expressed more frequently in IPN-L than in nonneoplastic bile ducts and nonpapillary ICC (P <0.01), and their incidence were significantly increased in parallel with the progression of IPN-L (P < 0.01). In contrast, expression of CK 7, a biliary marker, was decreased in IPN-L compared with nonpapillary ICC. Nuclear p53 immunostaining was detected in 30% of IPN-L as a whole and increased in tandem with the progression of IPN-L (P < 0.01). It is suggested that IPN-L forms a spectrum of biliary epithelial neoplasia with frequent gastrointestinal metaplasia, different from the usual nonpapillary ICC, and shows stepwise progression from the perspective of mucin profile, gastrointestinal metaplasia, and p53 nuclear expression. PMID:12094375

  15. Altered pressure pain thresholds and increased wind-up in adult patients with chronic back pain with a history of childhood maltreatment: a quantitative sensory testing study.

    PubMed

    Tesarz, Jonas; Eich, Wolfgang; Treede, Rolf-Detlef; Gerhardt, Andreas

    2016-08-01

    Childhood maltreatment (CM) has been associated with an increased risk of nonspecific chronic low back pain (nsCLBP). However, the mechanisms underlying this association are unclear. Therefore, this study considered whether distinct types of CM are accompanied by specific alterations in somatosensory function. A total of 176 subjects with nsCLBP and 27 pain-free controls (PCs) were included. The Childhood Trauma Questionnaire (CTQ) was used to categorize patients into 2 groups (abused/neglected vs nonabused/nonneglected) for 5 types of CM (emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect). The standardized quantitative sensory testing protocol of the "German Research Network on Neuropathic Pain" was performed to obtain comprehensive profiles on somatosensory function, including detection and pain thresholds, pain sensitivity, and assessments of temporal summation (wind-up). Between 17.7% and 51.4% of subjects with nsCLBP reported CM, depending on the type of CM. Childhood Trauma Questionnaire subscores for emotional and sexual abuse were significantly higher in subjects with nsCLBP than in PCs. Compared with PCs, subjects with CM showed reduced pressure pain thresholds (PPTs), irrespective of the type of CM. Regarding distinct types of CM, subjects with nsCLBP with emotional abuse reported significantly higher wind-up than those without, and sexual abuse was accompanied by enhanced touch sensitivity. Our findings suggest that CM is nonspecifically associated with a decreased PPT in nsCLBP. Emotional abuse apparently leads to enhanced spinal pain summation, and sexual abuse leads to enhanced touch sensitivity. These results emphasize the importance of emotional abuse in nsCLBP and suggest that CM can induce long-term changes in adult somatosensory function. PMID:27075429

  16. Fatty liver accompanies an increase of Lactobacillus acidophilus in the hind gut of C57/BL mice fed a high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High-fat diets can produce obesity and have been linked to the development of nonalcoholic fatty liver disease (NAFLD), which also induces changes in the gut microbiome. This study tested the hypothesis that high-fat feeding increases certain predominate hind gut bacteria in a C57BL/6 mouse model o...

  17. Increases in the serum acute phase proteins after ozone exposure are associated with induction of genes in the lung but not liver

    EPA Science Inventory

    Acute Phase Response (APR), a systemic reaction to infection, trauma, and inflammation, is characterized by increases and decreases in plasma levels of positive and negative acute phase proteins (APP), respectively. Although the liver has been shown to contribute to APR in variou...

  18. Increased accumulation of fumonisin B1, sphingoid bases and sphingoid base 1-phosphates: explaining the differential sensitivity of rat kidney and liver to fumonisin toxicity.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisins are mycotoxins in maize and inhibitors of ceramide synthase a key enzyme in the de novo sphingolipid biosynthesis pathway. In liver and kidney inhibition of ceramide synthase results in a marked increase in the ceramide precursor sphinganine. This study was conducted to investigate the di...

  19. Childhood obesity.

    PubMed

    Seth, Anju; Sharma, Rajni

    2013-04-01

    Childhood obesity is an issue of serious medical and social concern. In developing countries including India, it is a phenomenon seen in higher socioeconomic strata due to the adoption of a western lifestyle. Consumption of high calorie food, lack of physical activity and increased screen time are major risk factors for childhood obesity apart from other genetic, prenatal factors and socio-cultural practices. Obese children and adolescents are at increased risk of medical and psychological complications. Insulin resistance is commonly present especially in those with central obesity and manifests as dyslipidemia, type 2 diabetes mellitus, impaired glucose tolerance, hypertension, polycystic ovarian syndrome and metabolic syndrome. Obese children and adolescents often present to general physicians for management. The latter play a key role in prevention and treatment of obesity as it involves lifestyle modification of the entire family. This article aims at discussing the approach to diagnosis and work-up, treatment and preventive strategies for childhood obesity from a general physician's perspective. PMID:23255079

  20. Protective effects of protostemonine on LPS/GalN-induced acute liver failure: Roles of increased hepatic expression of heme oxygenase-1.

    PubMed

    Cheng, Zhuo; Yue, Ling; Zhao, Wenhao; Yang, Xinzhou; Shu, Guangwen

    2015-12-01

    Here, we explored protective effects of protostemonine (PSN), on mouse acute liver failure induced by lipopolysaccharide/d-galactosamine (LPS/GalN). PSN dose-dependently declined LPS/GalN-induced lethality of mice as well as increase of ALT/AST activities in their serum. Hepatoprotective effects of PSN were also supported by liver histopathological examinations. After LPS/GalN treatment, severe oxidative stresses in the liver could be detected by boosted MDA and ROS as well as decreased GSH. Moreover, hepatic expression of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, were sharply elevated. These symptoms were dose-dependently ameliorated by PSN. Mechanistically, PSN promoted the transcription and translation of heme oxygenase-1 (HO-1) in hepatocytes and liver Kupffer cells. Nrf2 is a master transcription factor contributing to the expression of HO-1. PSN elevated Nrf2 nuclear accumulation and enhanced Nrf2/HO-1 promoter interaction. Suppressing enzyme activity of HO-1 by co-treating mice with HO-1 inhibitor ZnPP abolished protective effects of PSN. ZnPP also abrogated alleviative impacts of PSN on LPS/GalN-mediated hepatic oxidative stresses and inflammatory responses. Finally, we showed that PSN exhibited undetectable toxic effects on vital organs of mice. Our findings suggested that PSN is able to attenuate LPS/GalN-induced acute liver failure and upregulating HO-1 expression is implicated in its hepatoprotective activity. PMID:26363973

  1. Ischemic preconditioning of rat livers from non-heart-beating donors decreases parenchymal cell killing and increases graft survival after transplantation.

    PubMed

    Currin, Robert T; Peng, Xing-Xi; Lemasters, John J

    2012-01-01

    A critical shortage of donors exists for liver transplantation, which non-heart-beating cadaver donors could help ease. This study evaluated ischemic preconditioning to improve graft viability after non-heart-beating liver donation in rats. Ischemic preconditioning was performed by clamping the portal vein and hepatic artery for 10 min followed by unclamping for 5 min. Subsequently, the aorta was cross-clamped for up to 120 min. After 2 h of storage, livers were either transplanted or perfused with warm buffer containing trypan blue. Aortic clamping for 60 and 120 min prior to liver harvest markedly decreased 30-day graft survival from 100% without aortic clamping to 50% and 0%, respectively, which ischemic preconditioning restored to 100 and 50%. After 60 min of aortic clamping, loss of viability of parenchymal and nonparenchymal cells was 22.6 and 5.6%, respectively, which preconditioning decreased to 3.0 and 1.5%. Cold storage after aortic clamping further increased parenchymal and non-parenchymal cell killing to 40.4 and 10.1%, respectively, which ischemic preconditioning decreased to 12.4 and 1.8%. In conclusion, ischemic preconditioning markedly decreased cell killing after subsequent sustained warm ischemia. Most importantly, ischemic preconditioning restored 100% graft survival of livers harvested from non-heart-beating donors after 60 min of aortic clamping. PMID:22888183

  2. Preexposure to Olive Oil Polyphenols Extract Increases Oxidative Load and Improves Liver Mass Restoration after Hepatectomy in Mice via Stress-Sensitive Genes

    PubMed Central

    Marinić, Jelena; Broznić, Dalibor; Milin, Čedomila

    2016-01-01

    Polyphenols can act as oxidants in some conditions, inducing redox-sensitive genes. We investigated the effect of preexposure to the olive oil polyphenols extract (PFE) on time-dependent changes in the hepatic oxidative state in a model of liver regeneration—a process in which oxidative stress associated with the metabolic overload accounts for the early events that contribute to the onset of liver self-repair. Liver regeneration was induced by one-third hepatectomy in mice. Prior to hepatectomy, mice were intraperitoneally given either PFE (50 mg/kg body weight) or saline for seven consecutive days, while respective controls received vehicle alone. Redox state-regulating enzymes and thiol proteins along with the mRNA levels of Nrf2 gene and its targets γ-glutamylcysteine synthetase and heme oxygenase-1 were determined at different time intervals after hepatectomy. The liver mass restoration was calculated to assess hepatic regeneration. The resulting data demonstrate the effectiveness of preexposure to PFE in stimulating liver regeneration in a model of a small tissue loss which may be ascribed to the transient increase in oxidant load during the first hours after hepatectomy and associated induction of stress response gene-profiles under the control of Nrf2. PMID:26925195

  3. Nonalcoholic Fatty Liver Disease is Associated with Increased Carotid Intima-Media Thickness in Type 1 Diabetic Patients

    PubMed Central

    Zhang, Lei; Guo, Kaifeng; Lu, Junxi; Zhao, Fangya; Yu, Haoyong; Han, Junfeng; Bao, Yuqian; Chen, Haibing; Jia, Weiping

    2016-01-01

    A growing body of evidence suggests that NAFLD is associated with an increased risk of incident CVD events both in patients without diabetes and in those with type 2 diabetes (T2DM). However, no published data are available regarding the association between NAFLD and C-IMT in T1DM. A total of 722 patients (371 men) with T1DM were included in this cross-sectional study. The main outcome measures were detection of NAFLD, C-IMT and classical risk factors. The mean age of the subjects was 46.2 years, and 51.1% were male. The prevalence of NAFLD was 15.9%. NAFLD patients had a markedly greater C-IMT (0.81 ± 0.25 vs. 0.69 ± 0.18 mm; p < 0.001) and frequency of carotid plaque (28.9% vs. 16.9%; p < 0.05) than those without fatty liver. Moreover, the differences in C-IMT remained after adjusting for potential confounders. A stepwise linear regression analysis revealed that age (standardized β, 0.326; p < 0.001), NAFLD (standardized β, 0.151, p < 0.001), and hsCRP (standardized β, 0.115, p = 0.008) were independently associated with C-IMT in all subjects. Our data show NAFLD is associated with elevated C-IMT in T1DM independent of conventional cardiovascular disease risk factors. PMID:27226159

  4. Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice

    PubMed Central

    Ferreira, Sandra M.; Vettorazzi, Jean F.; Nardelli, Tarlliza R.; Araujo, Hygor N.; Santos, Gustavo J.; Carneiro, Everardo M.; Boschero, Antonio C.; Rezende, Luiz F.; Costa-Júnior, José M.

    2016-01-01

    The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60–70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt, pathway was increased in the liver and skeletal muscle of trained mice. In an apparent contrast to the reduced insulinemia, glucose-stimulated insulin secretion was increased in isolated islets of these mice. However, insulin clearance was increased after acute exercise and was accompanied by increased expression of the insulin-degrading enzyme (IDE), in the liver and skeletal muscle. Finally, C2C12, but not HEPG2 cells, incubated at different concentrations of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 3-h, showed increased expression of IDE. In conclusion, acute exercise increases insulin clearance, probably due to an augmentation of IDE expression in the liver and skeletal muscle. The elevated IDE expression, in the skeletal muscle, seems to be mediated by activation of AMPK-ACC pathway, in response to exercise. We believe that the increase in the IDE expression, comprise a safety measure to maintain glycemia at or close to physiological levels, turning physical exercise more effective and safe. PMID:27467214

  5. Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice.

    PubMed

    Kurauti, Mirian A; Freitas-Dias, Ricardo; Ferreira, Sandra M; Vettorazzi, Jean F; Nardelli, Tarlliza R; Araujo, Hygor N; Santos, Gustavo J; Carneiro, Everardo M; Boschero, Antonio C; Rezende, Luiz F; Costa-Júnior, José M

    2016-01-01

    The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60-70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt, pathway was increased in the liver and skeletal muscle of trained mice. In an apparent contrast to the reduced insulinemia, glucose-stimulated insulin secretion was increased in isolated islets of these mice. However, insulin clearance was increased after acute exercise and was accompanied by increased expression of the insulin-degrading enzyme (IDE), in the liver and skeletal muscle. Finally, C2C12, but not HEPG2 cells, incubated at different concentrations of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 3-h, showed increased expression of IDE. In conclusion, acute exercise increases insulin clearance, probably due to an augmentation of IDE expression in the liver and skeletal muscle. The elevated IDE expression, in the skeletal muscle, seems to be mediated by activation of AMPK-ACC pathway, in response to exercise. We believe that the increase in the IDE expression, comprise a safety measure to maintain glycemia at or close to physiological levels, turning physical exercise more effective and safe. PMID:27467214

  6. Increased placental fatty acid transporter 6 and binding protein 3 expression and fetal liver lipid accumulation in a mouse model of obesity in pregnancy.

    PubMed

    Díaz, Paula; Harris, Jessica; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-12-15

    Obesity in pregnancy is associated with increased fetal growth and adiposity, which, in part, is determined by transplacental nutrient supply. Trophoblast uptake and intracellular trafficking of lipids are dependent on placental fatty acid transport proteins (FATP), translocase (FAT/CD36), and fatty acid binding proteins (FABP). We hypothesized that maternal obesity in mice leads to increased placental expression of FAT/CD36, FATPs, and FABPs, and lipid accumulation in the fetal liver. C57/BL6J female mice were fed either a control (C; n = 10) or an obesogenic (OB; n = 10) high-fat, high-sugar diet before mating and throughout pregnancy. At E18.5, placentas and fetal livers were collected. Trophoblast plasma membranes (TPM) were isolated from placental homogenates. Expression of FAT/CD36 and FATP (TPM) and FABP (homogenates) was determined by immunoblotting. Gene expression was assessed by RT-quantitative PCR. Sections of fetal livers were stained for Oil Red O, and lipid droplets were quantified. TPM protein expression of FAT/CD36, FATP 2, and FATP 4 was comparable between C and OB groups. Conversely, TPM FATP 6 expression was increased by 35% in OB compared with C placentas without changes in mRNA expression. FABPs 1, 3-5 and PPARγ were expressed in homogenates, and FABP 3 expression increased 27% in OB compared with C placentas; however, no changes were observed in mRNA expression. Lipid droplet accumulation was 10-fold higher in the livers of fetuses from OB compared with C group. We propose that increased lipid transport capacity in obese mice promotes transplacental fatty acid transport and contributes to excess lipid accumulation in the fetal liver. PMID:26491104

  7. Glucose-6-phosphatase mRNA and activity are increased to the same extent in kidney and liver of diabetic rats.

    PubMed

    Mithieux, G; Vidal, H; Zitoun, C; Bruni, N; Daniele, N; Minassian, C

    1996-07-01

    Using Northern blot with a specific glucose-6-phosphatase (Glc6Pase) cDNA probe and enzymatic activity determination, we studied the effect of streptozotocin-induced diabetes on Glc6Pase in rat gluconeogenic tissues. The Glc6Pase mRNA abundance was increased four to five times in both the liver and kidney of diabetic rats. This was correlated with a concomitant 130% increase in Glc6Pase catalytic subunit in both tissues. The elevated level of Glc6Pase mRNA was significantly corrected in both the liver and kidney of diabetic rats after a 12-h insulin treatment. We also studied Glc6Pase mRNA and activity in gluconeogenic tissues during the fed-fasted and fasted-refed transitions in normal rats. In the liver, the abundance of Glc6Pase mRNA was sharply increased about four times after 24 or 48 h of fasting. In the kidney, the Glc6Pase mRNA level was gradually increased some three and five times after 24 and 48 h of fasting, respectively. The increase of Glc6Pase mRNA in both organs was matched with a doubling of the activity of Glc6Pase catalytic subunit: rapid in the liver and gradual in the kidney. The liver Glc6Pase mRNA abundance in 48-h fasted rats was acutely and importantly decreased upon refeeding. The kidney Glc6Pase mRNA level was also significantly lowered under these conditions, albeit less rapidly. These data demonstrate that efficient control of Glc6Pase takes place in both gluconeogenic organs at the pretranslational level and suggest that insulin might play an important role in this control. In addition, using reverse transcription-polymerase chain reaction and Northern blot, we report that Glc6Pase mRNA is not detectable in several other tissues previously assumed to express the enzyme. PMID:8666139

  8. Decreased bile-acid synthesis in livers of hepatocyte-conditional NADPH-cytochrome P450 reductase-null mice results in increased bile acids in serum.

    PubMed

    Cheng, Xingguo; Zhang, Youcai; Klaassen, Curtis D

    2014-10-01

    NADPH-cytochrome P450 reductase (Cpr) is essential for the function of microsomal cytochrome P450 monooxygenases (P450), including those P450s involved in bile acid (BA) synthesis. Mice with hepatocyte-specific deletion of NADPH-cytochrome P450 reductase (H-Cpr-null) have been engineered to understand the in vivo function of hepatic P450s in the metabolism of xenobiotics and endogenous compounds. However, the impact of hepatic Cpr on BA homeostasis is not clear. The present study revealed that H-Cpr-null mice had a 60% decrease in total BA concentration in liver, whereas the total BA concentration in serum was almost doubled. The decreased level of cholic acid (CA) in both serum and livers of H-Cpr-null mice is likely due to diminished enzyme activity of Cyp8b1 that is essential for CA biosynthesis. Feedback mechanisms responsible for the reduced liver BA concentrations and/or increased serum BA concentrations in H-Cpr-null mice included the following: 1) enhanced alternative BA synthesis pathway, as evidenced by the fact that classic BA synthesis is diminished but chenodeoxycholic acid still increases in both serum and livers of H-Cpr-null mice; 2) inhibition of farnesoid X receptor activation, which increased the mRNA of Cyp7a1 and 8b1; 3) induction of intestinal BA transporters to facilitate BA absorption from the intestine to the circulation; 4) induction of hepatic multidrug resistance-associated protein transporters to increase BA efflux from the liver to blood; and 5) increased generation of secondary BAs. In summary, the present study reveals an important contribution of the alternative BA synthesis pathway and BA transporters in regulating BA concentrations in H-Cpr-null mice. PMID:25034404

  9. Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Berlanga, Alba; Guiu-Jurado, Esther; Martinez, Salomé; Armengol, Sandra; Sabench, Fàtima; Ras, Rosa; Hernandez, Mercè; Aguilar, Carmen; Colom, Josep; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS) and steatohepatitis (NASH) cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients. Materials and Methods We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30) and morbidly obese women (n = 97) with or without NAFLD. Results We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, there was no difference between SS and NASH. Moreover, we observed that circulating levels of alpha-ketoglutarate were associated with glucose metabolism parameters, lipid profile, hepatic enzymes and steatosis degree. In addition, diagnostic performance of alpha-ketoglutarate has been analyzed in NAFLD patients. The AUROC curves from patients with liver steatosis exhibited an acceptable clinical utility. Finally, we showed that the combination of biomarkers (AST, ALT and alpha-ketoglutarate) had the highest accuracy in diagnosing liver steatosis. Conclusion These findings suggest that alpha-ketoglutarate can determine the presence of non-alcoholic fatty liver in morbidly obese patients but it is not valid a biomarker for NASH. PMID:27123846

  10. Steeper increases in body mass index during childhood correlate with blood pressure elevation in adolescence: a long-term follow-up study in a Japanese community.

    PubMed

    Kuwahara, Erika; Asakura, Keiko; Nishiwaki, Yuji; Komatsu, Hirokazu; Nakazawa, Akemi; Ushiku, Hideo; Maejima, Fumio; Nishigaki, Yoshio; Hasegawa, Tomonobu; Okamura, Tomonori; Takebayashi, Toru

    2014-02-01

    The aim of this study was to clarify the relationship between long-term changes in body mass index (BMI) during childhood and adolescent blood-pressure levels in a general Japanese population. We used health report data from 900 Japanese children between 1983 and 2007. After adjusting for baseline BMI and other confounding factors multivariate linear regression analyses were performed to examine the relationship between changes in BMI (ΔBMI) over a 6-year period (6-12 years) and blood pressure once children reached ages 14 or 15. Sub-group analyses were also performed to ascertain the relationship between ΔBMI and blood pressure at 9th grade for children who had been in the bottom BMI tertile at 1st grade. Endpoint blood-pressure levels in boys (systolic and diastolic) and girls (systolic) from the group whose BMIs increased the most were significantly higher than those from the group whose BMIs increased the least (P<0.05, analysis of variance). After adjustment for baseline BMI and school-entrance year, the former group showed higher blood pressure at the endpoint than the latter (P<0.05, multiple regression analysis). Further adjustment for baseline blood pressure also showed similar results in a combined-sex analysis (n=592). Higher ΔBMI was associated with higher SBP9 even in children whose BMI was in the lowest tertile at baseline after adjustment for sex and school-entrance year (P=0.02, multiple regression analysis). Steeper BMI increases during primary school lead to adolescent increases in blood pressure even if baseline BMI is low. Growth during childhood should be carefully managed. PMID:24026043

  11. Soluble CD163 is not increased in visceral fat and steatotic liver and is even suppressed by free fatty acids in vitro.

    PubMed

    Bauer, Sabrina; Weiss, Thomas S; Wiest, Reiner; Schacherer, Doris; Hellerbrand, Claus; Farkas, Stefan; Scherer, Marcus N; Ritter, Mirko; Schmitz, Gerd; Schäffler, Andreas; Buechler, Christa

    2011-12-01

    Visceral fat differs from subcutaneous fat by higher local inflammation and increased release of IL-6 and free fatty acids (FFA) which contribute to hepatic steatosis. IL-6 has been shown to upregulate the monocyte/macrophage specific receptor CD163 whose soluble form, sCD163, is increased in inflammatory diseases. Here, it was analyzed whether CD163 and sCD163 are differentially expressed in the human fat depots and fatty liver. CD163 mRNA and protein were similarly expressed in paired samples of human visceral and subcutaneous fat, and comparable levels in portal venous and systemic venous blood of liver-healthy controls indicate that release of sCD163 from visceral adipose tissue was not increased. CD163 was also similarly expressed in steatotic liver when compared to non-steatotic tissues and sCD163 was almost equal in the respective sera. Concentrations of sCD163 were not affected when passing the liver excluding substantial hepatic removal/release of this protein. A high concentration of IL-6 upregulated CD163 protein while physiological doses had no effect. However, sCD163 was not increased by any of the IL-6 doses tested. FFA even modestly decreased CD163 and sCD163. The anti-inflammatory mediators fenofibrate, pioglitazone, and eicosapentaenoic acid (EPA) did not influence sCD163 levels while CD163 was reduced by EPA. These data suggest that in humans neither visceral fat nor fatty liver are major sources of sCD163. PMID:21839737

  12. Interaction of occupational manganese exposure and alcohol drinking aggravates the increase of liver enzyme concentrations from a cross-sectional study in China

    PubMed Central

    2013-01-01

    Background Over exposure to manganese (Mn) can damage the human central nervous system and potentially cause liver toxicity. Alcohol drinking is also one of the well-known harmful factors to hepatic organism. The interaction between Mn exposure and alcohol consumption to liver function was investigated in this study. Methods A total of 1112 on-the-spot workers were included in the cross-sectional survey from a large scale of manganese exposed workers healthy cohort (MEWHC) in a ferro-manganese refinery company. A questionnaire was used to collect the demographic information, occupational history, and alcohol drinking habits. Occupational health examination was carried out for each worker. The five key serum indices, including total bilirubin (TBILI), direct bilirubin (DBILI), indirect bilirubin (IBILI), alanine transaminase (ALT), and aspartate transaminase (AST), were determined to evaluate the liver function of each subject. Results Workers exposed to high levels of Mn had significantly elevated serum concentrations of liver enzymes (DBILI: 3.84±1.20 μmol/L, ALT: 27.04±19.12 IU/L, and AST: 29.96±16.68 IU/L), when compared to those in the low-exposure group (DBIL: 3.54±0.85 μmol/L, ALT: 20.38±10.97 IU/L, and AST: 26.39±8.07 IU/L), all P<0.01. These serum indices had a significantly increasing trend with the elevation of Mn exposure level (Ptrend <0.01). In addition, the workers with alcohol drinking also showed higher concentrations of liver enzymes than those non-drinkers, especially, and there was significant interaction between Mn exposure and alcohol consumption in terms of these three indices (P<0.001). Conclusions Occupational exposure to Mn can lead to a dose-dependent increase of liver enzyme concentrations, and interact with alcohol drinking to potentially aggravate the liver damage. It will be important for Mn exposed workers to control drinking and also assess liver function in the occupational health examination. PMID:23587294

  13. Liver Panel

    MedlinePlus

    ... liver; the best test for detecting hepatitis Alkaline phosphatase (ALP) – an enzyme related to the bile ducts ... only moderately elevated or close to normal. Alkaline phosphatase (ALP) ALP may be significantly increased with obstructed ...

  14. Immunizing pigs with Ascaris suum hemoglobin increases the inflammatory response in the liver but fails to induce a protective immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine whether purified Ascaris suum hemoglobin (AsHb) is a suitable vaccine candidate for the control of Ascaris infections, pigs were 30 vaccinated with AsHb in combination with QuilA adjuvant and challenged with A. suum eggs. The number of liver lesions and worms in the intestine was assess...

  15. Boron (B) deprivation increases plasma homocysteine and decreases liver S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The diverse effects of B deprivation suggest that B affects a biomolecule involved in a variety of biochemical reactions. An experiment was conducted to determine whether dietary B affects the liver concentration of SAM, a frequently used enzyme substrate, especially for methylation reactions that y...

  16. Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68+ Cells during Chronic HBV Infection

    PubMed Central

    Said, Elias A.; Al-Reesi, Iman; Al-Riyami, Marwa; Al-Naamani, Khalid; Al-Sinawi, Shadia; Al-Balushi, Mohammed S.; Koh, Crystal Y.; Al-Busaidi, Juma Z.; Idris, Mohamed A.; Al-Jabri, Ali A.

    2016-01-01

    Background The failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68+ cells has not been explored in HBV-infected livers. Methods Double staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas. Results Chronic HBV infection was associated with increased CD68+CD86+ cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68+CD80+ and CD68+PD-L1+ cells, compared to the control group. While CD68+CD80+ cell count in portal areas correlated with the fibrosis score, CD68+CD80+ cell percentage in lobular areas correlated with the inflammation grade. Conclusion The upregulation of CD86 but not CD80 and PD-L1 on CD68+ cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68+ cells correlates with liver inflammation and fibrosis. PMID:27348308

  17. Consumption of sucrose and high-fructose corn syrup does not increase liver fat or ectopic fat deposition in muscles.

    PubMed

    Bravo, Stephen; Lowndes, Joshua; Sinnett, Stephanie; Yu, Zhiping; Rippe, James

    2013-06-01

    It has been postulated that fructose-induced triglyceride synthesis is augmented when accompanied by glucose. Chronic elevations could lead to excess fat accumulation in the liver and ectopic fat deposition in muscles, which in turn could contribute to the induction of abnormalities in glucose homeostasis, insulin resistance, and the subsequent development of type 2 diabetes. Our objective was to evaluate the effect of the addition of commonly consumed fructose- and (or) glucose-containing sugars in the usual diet on liver fat content and intramuscular adipose tissue. For 10 weeks, 64 individuals (mean age, 42.16 ± 11.66 years) consumed low-fat milk sweetened with either high-fructose corn syrup (HFCS) or sucrose; the added sugar matched consumption levels of fructose in the 25th, 50th, and 90th percentiles of the population. The fat content of the liver was measured with unenhanced computed tomography imaging, and the fat content of muscle was assessed with magnetic resonance imaging. When the 6 HFCS and sucrose groups were averaged, there was no change over the course of 10 weeks in the fat content of the liver (13.32% ± 10.49% vs. 13.21% ± 10.75%; p > 0.05), vastus lateralis muscle (3.07 ± 0.74 g per 100 mL vs. 3.15 ± 0.84 g per 100 mL; p > 0.05), or gluteus maximus muscle (4.08 ± 1.50 g per 100 mL vs. 4.24 ± 1.42 g per 100 mL; p > 0.05). Group assignment did not affect the result (interaction > 0.05). These data suggest that when fructose is consumed as part of a typical diet in normally consumed sweeteners, such as sucrose or HFCS, ectopic fat storage in the liver or muscles is not promoted. PMID:23724887

  18. Increased hepatic receptor interacting protein kinase 3 expression due to impaired proteasomal functions contributes to alcohol-induced steatosis and liver injury

    PubMed Central

    Wang, Shaogui; Ni, Hong-Min; Dorko, Kenneth; Kumer, Sean C.; Schmitt, Timothy M.; Nawabi, Atta; Komatsu, Masaaki; Huang, Heqing; Ding, Wen-Xing

    2016-01-01

    Chronic alcohol exposure increased hepatic receptor-interacting protein kinase (RIP) 3 expression and necroptosis in the liver but its mechanisms are unclear. In the present study, we demonstrated that chronic alcohol feeding plus binge (Gao-binge) increased RIP3 but not RIP1 protein levels in mouse livers. RIP3 knockout mice had decreased serum alanine amino transferase activity and hepatic steatosis but had no effect on hepatic neutrophil infiltration compared with wild type mice after Gao-binge alcohol treatment. The hepatic mRNA levels of RIP3 did not change between Gao-binge and control mice, suggesting that alcohol-induced hepatic RIP3 proteins are regulated at the posttranslational level. We found that Gao-binge treatment decreased the levels of proteasome subunit alpha type-2 (PSMA2) and proteasome 26S subunit, ATPase 1 (PSMC1) and impaired hepatic proteasome function. Pharmacological or genetic inhibition of proteasome resulted in the accumulation of RIP3 in mouse livers. More importantly, human alcoholics had decreased expression of PSMA2 and PSMC1 but increased protein levels of RIP3 compared with healthy human livers. Moreover, pharmacological inhibition of RIP1 decreased Gao-binge-induced hepatic inflammation, neutrophil infiltration and NF-κB subunit (p65) nuclear translocation but failed to protect against steatosis and liver injury induced by Gao-binge alcohol. In conclusion, results from this study suggest that impaired hepatic proteasome function by alcohol exposure may contribute to hepatic accumulation of RIP3 resulting in necroptosis and steatosis while RIP1 kinase activity is important for alcohol-induced inflammation. PMID:26769846

  19. Interferon-alpha 2b increases fibrolysis in fibrotic livers from bile duct ligated rats: possible participation of the plasminogen activator.

    PubMed

    Rodríguez-Fragoso, L; González, M P; Muriel, P

    1995-12-01

    Interferons are known to prevent liver collagen by an antifibrogenic mechanism that involves mRNA procollagen regulation. The aim of the present work was to determine whether interferon could also decrease collagen by increasing its degradation. Fibrosis was induced in male Wistar rats by double ligation and section of the common bile duct. Interferon-alpha 2b (100,000 IU/rat s.c.) was administered to bile duct ligated rats daily after surgery for 4 weeks. Interferon increased the capacity of the liver to degrade type I and III collagens and matrigel. In addition, the plasminogen activator activity also increased. Since plasminogens are thought to be key participants in the balance of proteolytic activities that regulate extracellular matrix degradation, their elevation may also provide another antifibrotic (proteolytic) mechanism of action of interferon. PMID:8966190

  20. Inhibition of miR122a by Lactobacillus rhamnosus GG culture supernatant increases intestinal occludin expression and protects mice from alcoholic liver disease.

    PubMed

    Zhao, Haiyang; Zhao, Cuiqing; Dong, Yuanyuan; Zhang, Min; Wang, Yuhua; Li, Fengyuan; Li, Xiaokun; McClain, Craig; Yang, Shulin; Feng, Wenke

    2015-05-01

    Alcoholic liver disease (ALD) has a high morbidity and mortality. Chronic alcohol consumption causes disruption of intestinal microflora homeostasis, intestinal tight junction barrier dysfunction, increased endotoxemia, and eventually liver steatosis/steatohepatitis. Probiotic Lactobacillus rhamnosus GG (LGG) and the bacteria-free LGG culture supernatant (LGGs) have been shown to promote intestinal epithelial integrity and protect intestinal barrier function in ALD. However, little is known about how LGGs mechanistically works to increase intestinal tight junction proteins. Here we show that chronic ethanol exposure increased intestinal miR122a expression, which decreased occludin expression leading to increased intestinal permeability. Moreover, LGGs supplementation decreased ethanol-elevated miR122a level and attenuated ethanol-induced liver injury in mice. Similar to the effect of ethanol exposure, overexpression of miR122a in Caco-2 monolayers markedly decreased occludin protein levels. In contrast, inhibition of miR122a increased occludin expression. We conclude that LGGs supplementation functions in intestinal integrity by inhibition of miR122a, leading to occludin restoration in mice exposed to chronic ethanol. PMID:25746479

  1. Childhood obesity.

    PubMed

    Han, Joan C; Lawlor, Debbie A; Kimm, Sue Y S

    2010-05-15

    Worldwide prevalence of childhood obesity has increased greatly during the past three decades. The increasing occurrence in children of disorders such as type 2 diabetes is believed to be a consequence of this obesity epidemic. Much progress has been made in understanding of the genetics and physiology of appetite control and from these advances, elucidation of the causes of some rare obesity syndromes. However, these rare disorders have so far taught us few lessons about prevention or reversal of obesity in most children. Calorie intake and activity recommendations need reassessment and improved quantification at a population level because of sedentary lifestyles of children nowadays. For individual treatment, currently recommended calorie prescriptions might be too conservative in view of evolving insight into the so-called energy gap. Although quality of research into both prevention and treatment has improved, high-quality multicentre trials with long-term follow-up are needed. Meanwhile, prevention and treatment approaches to increase energy expenditure and decrease intake should continue. Recent data suggest that the spiralling increase in childhood obesity prevalence might be abating; increased efforts should be made on all fronts to continue this potentially exciting trend. PMID:20451244

  2. Periportal CD4+ cell infiltration increases in HIV/hepatitis C virus-coinfected patients commencing ART, whereas CD8+ cells clear from the liver.

    PubMed

    Gani, Rino A; Yunihastuti, Evy; Krisnuhoni, Ening; Saraswati, Henny; Djauzi, Sjamsurizal; Lesmana, Laurentius A; Lee, Silvia; Price, Patricia

    2014-08-01

    Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common in Asia, but the effects of antiretroviral therapy (ART) are unclear. Histopathological changes in the liver are described in a prospective study of HCV-seropositive HIV-infected patients at Cipto Mangunkusomo Hospital (Jakarta, Indonesia). Liver biopsy specimens were collected at baseline (n = 48) and 48 weeks (n = 34). Ishak scores showed mild but detectable inflammation and/or fibrosis. Levels of portal inflammation declined during ART (P = .03), whereas fibrosis remained (P = .11). Portal infiltration of CD4(+) cells increased during ART (P < .0001), whereas infiltration of CD8(+) cells subsided. Numbers of CD4(+) cells in the liver at baseline correlated with circulating CD4(+) T-cell counts (P = .03-.05). Numbers of liver-infiltrating CD4(+) and CD8(+) cells at baseline were not associates with subsequent experience of an immune restoration disease, which is defined by a rise in alanine transaminase levels during ART. PMID:24585895

  3. Protein kinase C is increased in the liver of humans and rats with non-insulin-dependent diabetes mellitus: an alteration not due to hyperglycemia.

    PubMed Central

    Considine, R V; Nyce, M R; Allen, L E; Morales, L M; Triester, S; Serrano, J; Colberg, J; Lanza-Jacoby, S; Caro, J F

    1995-01-01

    We tested the hypothesis that liver protein kinase C (PKC) is increased in non-insulin-dependent diabetes mellitus (NIDDM). To this end we examined the distribution of PKC isozymes in liver biopsies from obese individuals with and without NIDDM and in lean controls. PKC isozymes alpha, beta, epsilon and zeta were detected by immunoblotting in both the cytosol and membrane fractions. Isozymes gamma and delta were not detected. There was a significant increase in immunodetectable PKC-alpha (twofold), -epsilon (threefold), and -zeta (twofold) in the membrane fraction isolated from obese subjects with NIDDM compared with the lean controls. In obese subjects without NIDDM, the amount of membrane PKC isozymes was not different from the other two groups. We next sought an animal model where this observation could be studied further. The Zucker diabetic fatty rat offered such a model system. Immunodetectable membrane PKC-alpha, -beta, -epsilon, and -zeta were significantly increased when compared with both the lean and obese controls. The increase in immunodetectable PKC protein correlated with a 40% elevation in the activity of PKC at the membrane. Normalization of circulating glucose in the rat model by either insulin or phlorizin treatment did not result in a reduction in membrane PKC isozyme protein or kinase activity. Further, phlorizin treatment did not improve insulin receptor autophosphorylation nor did the treatment lower liver diacylglycerol. We conclude that liver PKC is increased in NIDDM, a change that is not secondary to hyperglycemia. It is possible that PKC-mediated phosphorylation of some component in the insulin signaling cascade contributes to the insulin resistance observed in NIDDM. Images PMID:7769136

  4. H. hepaticus-induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response

    PubMed Central

    García, Alexis; Zeng, Yu; Muthupalani, Sureshkumar; Ge, Zhongming; Potter, Amanda; Mobley, Melissa W.; Boussahmain, Chakib; Feng, Yan; Wishnok, John S.; Fox, James G.

    2011-01-01

    Chronic microbial infection influence cancer progression but the mechanisms that link them remain unclear. Constitutive androstane receptor (CAR) is a nuclear receptor that regulates enzymes involved in endobiotic and xenobiotic metabolism. CAR activation is a mechanism of xenobiotic tumor promotion, however, the effects of chronic microbial infection on tumor promotion have not been studied in the context of CAR function. Here we report that CAR limits the effects of chronic infection-associated progression of liver cancer. CAR knockout (KO) and wild-type (WT) male mice were treated or not with the tumor initiator diethylnitrosamine (DEN) at 5 weeks of age and then orally inoculated with Helicobacter hepaticus (Hh) or sterile media at 8 weeks of age. At 50 weeks postinoculation mice were euthanized for histopathological, microbiological, molecular, and metabolomic analyses. Hh infection induced comparable hepatitis in WT and KO mice with or without DEN that correlated with significant upregulation of Tnfα and toll receptor Tlr2. Notably, DEN-treated Hh-infected KO mice exhibited increased numbers of liver lobes with dysplasia and neoplasia, as well as increased multiplicity of neoplasia, relative to similarly treated WT mice. Enhanced tumor promotion was associated with decreased hepatic expression of P450 enzymes Cyp2b10 and Cyp3a11, increased expression of Camp, and increased serum concentrations of chenodeoxycholic acid. Together, our findings suggest that liver tumor promotion is enhanced by an impaired metabolic detoxification of endobiotics and a persistent microbial-induced immune response. PMID:21335546

  5. Dietary quebracho tannins are not absorbed, but increase the antioxidant capacity of liver and plasma in sheep.

    PubMed

    López-Andrés, Patricia; Luciano, Giuseppe; Vasta, Valentina; Gibson, Trevor M; Biondi, Luisa; Priolo, Alessandro; Mueller-Harvey, Irene

    2013-08-01

    A total of sixteen lambs were divided into two groups and fed two different diets. Of these, eight lambs were fed a control diet (C) and eight lambs were fed the C diet supplemented with quebracho tannins (C+T). The objective of the present study was to assess whether dietary quebracho tannins can improve the antioxidant capacity of lamb liver and plasma and if such improvement is due to a direct transfer of phenolic compounds or their metabolites, to the animal tissues. Feed, liver and plasma samples were purified by solid-phase extraction (SPE) and analysed by liquid chromatography-MS for phenolic compounds. Profisitinidin compounds were identified in the C+T diet. However, no phenolic compounds were found in lamb tissues. The liver and the plasma from lambs fed the C+T diet displayed a greater antioxidant capacity than tissues from lambs fed the C diet, but only when samples were not purified with SPE. Profisetinidin tannins from quebracho seem not to be degraded or absorbed in the gastrointestinal tract. However, they induced antioxidant effects in animal tissues. PMID:23312208

  6. Researching Early Childhood Education: European Perspectives.

    ERIC Educational Resources Information Center

    David, Tricia, Ed.

    At a time when crucial questions concerning the nature of early childhood and early childhood education are being increasingly examined worldwide, an exploration of the issues, priorities, and methodologies of research in early childhood education may provide valuable material for debate. This book focuses on research in early childhood education…

  7. Pediatric fatty liver disease: Role of ethnicity and genetics

    PubMed Central

    Marzuillo, Pierluigi; Miraglia del Giudice, Emanuele; Santoro, Nicola

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver. PMID:24966605

  8. Increasing Levels of Dietary Hempseed Products Leads to Differential Responses in the Fatty Acid Profiles of Egg Yolk, Liver and Plasma of Laying Hens.

    PubMed

    Neijat, M; Suh, M; Neufeld, J; House, J D

    2016-05-01

    The limited efficiency with which dietary alpha-linolenic acid (ALA) is converted by hens into docosahexaenoic acid (DHA) for egg deposition is not clearly understood. In this study, dietary ALA levels were increased via the inclusion of hempseed (HS) and hempseed oil (HO) in hen diets, with the goal of assessing the effects on the fatty acid (FA) profiles of total lipids and lipid classes in yolk, liver and plasma. Forty-eight hens were individually caged and fed one of six diets containing either HS:10, 20 or 30, HO:4.5 or 9.0 (%, diet) or a control (containing corn oil), providing a range (0.1-1.28 %, diet) of ALA. Fatty acid methyl esters of total lipids and lipid classes, including phosphatidyl choline (PtdCho) and ethanolamine (PtdEtn) in yolk, plasma and liver were then determined. Levels of n-3 FAs in both total lipids and lipid classes increased in all tissues. ALA and eicosapentaenoic acid (EPA) increased linearly, while docosapentaenoic acid and DHA increased quadratically. The FA profiles of yolk closely reflected levels in both plasma and liver. While ALA was highly concentrated in the triacylglycerol, it was low but equally distributed between PtdCho and PtdEtn in all tissues; however, the net accumulation was lower (P < 0.0001) in liver compared to yolk and plasma. Levels of EPA and ALA in yolk-PtdEtn were linearly (P < 0.0001; R (2) = 0.93) associated, and reflected those in liver-PtdEtn (P < 0.0001; R (2) = 0.90). In the liver, a strong inverse correlation (P < 0.0001; r = -0.94) between PL-DHA and ALA-to-EPA ratio in PtdEtn supports theories of low substrate availability, possibly limiting the conversion of ALA into DHA for egg enrichment. PMID:27052441

  9. Ischaemia and reperfusion injury of rat liver increases expression of glutathione S-transferase A1/A2 in zone 3 of the hepatic lobule.

    PubMed Central

    Branum, G D; Selim, N; Liu, X; Whalen, R; Boyer, T D

    1998-01-01

    Effects of ischaemia-reperfusion injury (I/R) of liver on expression of rat glutathione S-transferase (rGST) isoenzymes that metabolize products of oxidative stress were examined. Rats underwent lobar liver ischaemia for 30 min followed by reperfusion. In ischaemic lobes, rGSTA1/A2 transcript levels increased significantly 12 h after I/R (2.94-fold) and protein levels increased significantly at 24 h (1.45-fold); increased transcript levels were also observed in nonischaemic lobes (1.78-fold). Superoxide dismutase prevented I/R and the increases in transcript and protein levels in ischaemic and non-ischaemic lobes. By in-situ hybridization, increases in transcript levels at 6 h were present in zones 2 and 3 of the ischaemic lobes and peaked at 12 h (2.5-fold zone 2, 4.5-fold zone 3). Significant increases in transcript levels also were observed at 24 h in zones 2 (2.0-fold) and 3 (2.9-fold) of non-ischaemic lobes. Nuclear run-off assays showed a 1.8-fold increase in rGSTA1/A2 transcription rates in ischaemic lobes at 3 h. We conclude that I/R causes increased rGSTA1/A2 expression in the zone of the hepatic lobule most susceptible to oxidative injury and that this expression may be an important defence against injury. PMID:9461493

  10. Liver disease in menopause

    PubMed Central

    Brady, Carla W

    2015-01-01

    There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure. PMID:26167064

  11. Childhood Obesity Associates Haemodynamic and Vascular Changes That Result in Increased Central Aortic Pressure with Augmented Incident and Reflected Wave Components, without Changes in Peripheral Amplification.

    PubMed

    Castro, Juan M; García-Espinosa, Victoria; Curcio, Santiago; Arana, Maite; Chiesa, Pedro; Giachetto, Gustavo; Zócalo, Yanina; Bia, Daniel

    2016-01-01

    The aims were to determine if childhood obesity is associated with increased central aortic blood pressure (BP) and to characterize haemodynamic and vascular changes associated with BP changes in obese children and adolescents by means of analyzing changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR), and net and relative contributions of reflected waves to the aortic pulse wave amplitude. We included 117 subjects (mean/range age: 10 (5-15) years, 49 females), who were obese (OB) or had normal weight (NW). Peripheral and central aortic BP, PWV, and pulse wave-derived parameters (augmentation index, amplitude of forward and backward components) were measured with tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). With independence of the presence of dyslipidemia, hypertension, or sedentarism, the aortic systolic and pulse BP were higher in OB than in NW subjects. The increase in central BP could not be explained by the elevation in the relative contribution of reflections to the aortic pressure wave and higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP could be explained by an increase in the amplitude of both incident and reflect wave components associated to augmented SV and/or PWV. PMID:26881081

  12. Childhood Obesity Associates Haemodynamic and Vascular Changes That Result in Increased Central Aortic Pressure with Augmented Incident and Reflected Wave Components, without Changes in Peripheral Amplification

    PubMed Central

    Castro, Juan M.; García-Espinosa, Victoria; Curcio, Santiago; Arana, Maite; Chiesa, Pedro; Giachetto, Gustavo; Zócalo, Yanina; Bia, Daniel

    2016-01-01

    The aims were to determine if childhood obesity is associated with increased central aortic blood pressure (BP) and to characterize haemodynamic and vascular changes associated with BP changes in obese children and adolescents by means of analyzing changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR), and net and relative contributions of reflected waves to the aortic pulse wave amplitude. We included 117 subjects (mean/range age: 10 (5–15) years, 49 females), who were obese (OB) or had normal weight (NW). Peripheral and central aortic BP, PWV, and pulse wave-derived parameters (augmentation index, amplitude of forward and backward components) were measured with tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). With independence of the presence of dyslipidemia, hypertension, or sedentarism, the aortic systolic and pulse BP were higher in OB than in NW subjects. The increase in central BP could not be explained by the elevation in the relative contribution of reflections to the aortic pressure wave and higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP could be explained by an increase in the amplitude of both incident and reflect wave components associated to augmented SV and/or PWV. PMID:26881081

  13. Socioeconomic position in childhood and cancer in adulthood: a rapid-review

    PubMed Central

    Vohra, Jyotsna; Marmot, Michael G; Bauld, Linda; Hiatt, Robert A

    2016-01-01

    Background The relationship of childhood socioeconomic position (SEP) to adult cancer has been inconsistent in the literature and there has been no review summarising the current evidence focused solely on cancer outcomes. Methods and results We performed a rapid review of the literature, which identified 22 publications from 13 studies, primarily in the UK and northern European countries that specifically analysed individual measures of SEP in childhood and cancer outcomes in adulthood. Most of these studies adjusted for adult SEP as a critical mediator of the relationship of interest. Conclusions Results confirm that childhood socioeconomic circumstances have a strong influence on stomach cancer and are likely to contribute, along with adult circumstances, to lung cancer through cumulative exposure to smoking. There was also some evidence of increased risk of colorectal, liver, cervical and pancreatic cancers with lower childhood SEP in large studies, but small numbers of cancer deaths made these estimates imprecise. Gaps in knowledge and potential policy implications are presented. PMID:26715591

  14. Increased diet-induced fatty streak formation in female mice with deficiency of liver-derived insulin-like growth factor-I.

    PubMed

    Svensson, Johan; Sjögren, Klara; Levin, Malin; Borén, Jan; Tivesten, Åsa; Ohlsson, Claes

    2016-06-01

    The role of endocrine IGF-I for atherosclerosis is unclear. We determined the importance of circulating, liver-derived IGF-I for fatty streak formation in mice. Mice with adult, liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice, serum IGF-I reduced by approximately 80 %) and control mice received an atherogenic (modified Paigen) diet between 6 and 12 months of age. At study end, Oil Red O staining of aortic root cryosections showed increased fatty streak area and lipid deposition in female but not in male LI-IGF-I(-/-) mice compared to controls. Mac-2 staining of aortic root and measurements of CD68 mRNA level in femoral artery revealed increased macrophage accumulation in proportion to the increased fatty streak area in female LI-IGF-I(-/-) mice. Moreover, female LI-IGF-I(-/-) mice displayed increased serum cholesterol and interleukin-6 as well as increased vascular cell-adhesion molecule 1 (VCAM1) mRNA levels in the femoral artery and elevated VCAM1 protein expression in the aortic root. Thus, increased diet-induced fatty streak formation in female LI-IGF-I(-/-) mice was associated with increased serum cholesterol and signs of systemic inflammation, endothelial activation, lipid deposition, and macrophage infiltration in the vascular wall. PMID:26627099

  15. Liver metabolomics reveals increased oxidative stress and fibrogenic potential in gfrp transgenic mice in response to ionizing radiation.

    PubMed

    Cheema, Amrita K; Pathak, Rupak; Zandkarimi, Fereshteh; Kaur, Prabhjit; Alkhalil, Lynn; Singh, Rajbir; Zhong, Xiaogang; Ghosh, Sanchita; Aykin-Burns, Nukhet; Hauer-Jensen, Martin

    2014-06-01

    Although radiation-induced tissue-specific injury is well documented, the underlying molecular changes resulting in organ dysfunction and the consequences thereof on overall metabolism and physiology have not been elucidated. We previously reported the generation and characterization of a transgenic mouse strain that ubiquitously overexpresses Gfrp (GTPH-1 feedback regulatory protein) and exhibits higher oxidative stress, which is a possible result of decreased tetrahydrobiopterin (BH4) bioavailability. In this study, we report genotype-dependent changes in the metabolic profiles of liver tissue after exposure to nonlethal doses of ionizing radiation. Using a combination of untargeted and targeted quantitative mass spectrometry, we report significant accumulation of metabolites associated with oxidative stress, as well as the dysregulation of lipid metabolism in transgenic mice after radiation exposure. The radiation stress seems to exacerbate lipid peroxidation and also results in higher expression of genes that facilitate liver fibrosis, in a manner that is dependent on the genetic background and post-irradiation time interval. These findings suggest the significance of Gfrp in regulating redox homeostasis in response to stress induced by ionizing radiation affecting overall physiology. PMID:24824572

  16. Liver Metabolomics Reveals Increased Oxidative Stress and Fibrogenic Potential in Gfrp Transgenic Mice in Response to Ionizing Radiation

    PubMed Central

    2015-01-01

    Although radiation-induced tissue-specific injury is well documented, the underlying molecular changes resulting in organ dysfunction and the consequences thereof on overall metabolism and physiology have not been elucidated. We previously reported the generation and characterization of a transgenic mouse strain that ubiquitously overexpresses Gfrp (GTPH-1 feedback regulatory protein) and exhibits higher oxidative stress, which is a possible result of decreased tetrahydrobiopterin (BH4) bioavailability. In this study, we report genotype-dependent changes in the metabolic profiles of liver tissue after exposure to nonlethal doses of ionizing radiation. Using a combination of untargeted and targeted quantitative mass spectrometry, we report significant accumulation of metabolites associated with oxidative stress, as well as the dysregulation of lipid metabolism in transgenic mice after radiation exposure. The radiation stress seems to exacerbate lipid peroxidation and also results in higher expression of genes that facilitate liver fibrosis, in a manner that is dependent on the genetic background and post-irradiation time interval. These findings suggest the significance of Gfrp in regulating redox homeostasis in response to stress induced by ionizing radiation affecting overall physiology. PMID:24824572

  17. Dietary L-carnitine supplementation increases lipid deposition in the liver and muscle of yellow catfish (Pelteobagrus fulvidraco) through changes in lipid metabolism.

    PubMed

    Zheng, Jia-Lang; Luo, Zhi; Zhuo, Mei-Qing; Pan, Ya-Xiong; Song, Yu-Feng; Hu, Wei; Chen, Qi-Liang

    2014-09-14

    Carnitine has been reported to improve growth performance and reduce body lipid content in fish. Thus, we hypothesised that carnitine supplementation can improve growth performance and reduce lipid content in the liver and muscle of yellow catfish (Pelteobagrus fulvidraco), a commonly cultured freshwater fish in inland China, and tested this hypothesis in the present study. Diets containing l-carnitine at three different concentrations of 47 mg/kg (control, without extra carnitine addition), 331 mg/kg (low carnitine) and 3495 mg/kg (high carnitine) diet were fed to yellow catfish for 8 weeks. The low-carnitine diet significantly improved weight gain (WG) and reduced the feed conversion ratio (FCR). In contrast, the high-carnitine diet did not affect WG and FCR. Compared with the control diet, the low-carnitine and high-carnitine diets increased lipid and carnitine contents in the liver and muscle. The increased lipid content in the liver could be attributed to the up-regulation of the mRNA levels of SREBP, PPARγ, fatty acid synthase (FAS) and ACCa and the increased activities of lipogenic enzymes (such as FAS, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and malic enzyme) and to the down-regulation of the mRNA levels of the lipolytic gene CPT1A. The increased lipid content in muscle could be attributed to the down-regulation of the mRNA levels of the lipolytic genes CPT1A and ATGL and the increased activity of lipoprotein lipase. In conclusion, in contrast to our hypothesis, dietary carnitine supplementation increased body lipid content in yellow catfish. PMID:24933091

  18. Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins

    PubMed Central

    Ouellet-Morin, I.; Wong, C. C. Y.; Danese, A.; Pariante, C. M.; Papadopoulos, A. S.; Mill, J.; Arseneault, L.

    2014-01-01

    Background Childhood adverse experiences are known to induce persistent changes in the hypothalamic–pituitary–adrenal (HPA) axis reactivity to stress. However, the mechanisms by which these experiences shape the neuroendocrine response to stress remain unclear. Method We tested whether bullying victimization influenced serotonin transporter gene (SERT) DNA methylation using a discordant monozygotic (MZ) twin design. A subsample of 28 MZ twin pairs discordant for bullying victimization, with data on cortisol and DNA methylation, were identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994–1995 cohort of families with twins. Results Bullied twins had higher SERT DNA methylation at the age of 10 years compared with their non-bullied MZ co-twins. This group difference cannot be attributed to the children’s genetic makeup or their shared familial environments because of the study design. Bullied twins also showed increasing methylation levels between the age of 5 years, prior to bullying victimization, and the age of 10 years whereas no such increase was detected in non-bullied twins across time. Moreover, children with higher SERT methylation levels had blunted cortisol responses to stress. Conclusions Our study extends findings drawn from animal models, supports the hypothesis that early-life stress modifies DNA methylation at a specific cytosine–phosphate–guanine (CpG) site in the SERT promoter and HPA functioning and suggests that these two systems may be functionally associated. PMID:23217646

  19. Pet ownership is associated with increased risk of non-atopic asthma and reduced risk of atopy in childhood: findings from a UK birth cohort

    PubMed Central

    Collin, S.M.; Granell, R; Westgarth, C; Murray, J; Paul, E; Sterne, J.A.C.; Henderson, A. John

    2014-01-01

    Background Studies have shown an inverse association of pet ownership with allergy but inconclusive findings for asthma. Objective To investigate whether pet ownership during pregnancy and childhood was associated with asthma and atopy at age 7 years in a UK population-based birth cohort. Methods Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to investigate associations of pet ownership at six time-points from pregnancy to age 7 years with asthma, atopy (grass, house-dust mite, and cat skin prick test) and atopic versus non-atopic asthma at age 7 years using logistic regression models adjusted for child's sex, maternal history of asthma/atopy, maternal smoking during pregnancy and family adversity. Results 3,768 children had complete data on pet ownership, asthma and atopy. Compared with non-ownership, continuous ownership of any pet (before and after age 3 years) was associated with 52% lower odds of atopic asthma (odds ratio [OR] 0.48, 95% CI 0.34–0.68). Pet ownership tended to be associated with increased risk of non-atopic asthma, particularly rabbits (OR 1.61, 1.04–2.51) and rodents (OR 1.86, 1.15–3.01), comparing continuous versus non-ownership. Pet ownership was consistently associated with lower odds of sensitization to grass, house-dust mite and cat allergens, but rodent ownership was associated with higher odds of sensitization to rodent allergen. Differential effects of pet ownership on atopic versus non-atopic asthma were evident for all pet types. Conclusions Pet ownership during pregnancy and childhood in this birth cohort was consistently associated with a reduced risk of aeroallergen sensitization and atopic asthma at age 7 years, but tended to be associated (particularly for rabbits and rodents) with an increased risk of non-atopic asthma. Clinical relevance The opposing effects on atopy versus non-atopic asthma might be considered by parents when they are deciding whether to acquire a pet. PMID:25077415

  20. Liver Cancer

    MedlinePlus

    ... body digest food, store energy, and remove poisons. Primary liver cancer starts in the liver. Metastatic liver ... and spreads to your liver. Risk factors for primary liver cancer include Having hepatitis B or C ...

  1. Liver scan

    MedlinePlus

    ... hyperplasia or adenoma of the liver Abscess Budd-Chiari syndrome Infection Liver disease (such as cirrhosis or ... Amebic liver abscess Cirrhosis Hepatic vein obstruction (Budd-Chiari) Hepatitis Liver cancer - hepatocellular carcinoma Liver disease Splenic ...

  2. Liver-Specific Deletion of Phosphatase and Tensin Homolog Deleted on Chromosome 10 Significantly Ameliorates Chronic EtOH-Induced Increases in Hepatocellular Damage.

    PubMed

    Shearn, Colin T; Orlicky, David J; McCullough, Rebecca L; Jiang, Hua; Maclean, Kenneth N; Mercer, Kelly E; Stiles, Bangyan L; Saba, Laura M; Ronis, Martin J; Petersen, Dennis R

    2016-01-01

    Alcoholic liver disease is a significant contributor to global liver failure. In murine models, chronic ethanol consumption dysregulates PTEN/Akt signaling. Hepatospecific deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTENLKO) mice possess constitutive activation of Akt(s) and increased de novo lipogenesis resulting in increased hepatocellular steatosis. This makes PTENLKO a viable model to examine the effects of ethanol in an environment of preexisting steatosis. The aim of this study was to determine the impact of chronic ethanol consumption and the absence of PTEN (PTENLKO) compared to Alb-Cre control mice (PTENf/f) on hepatocellular damage as evidenced by changes in lipid accumulation, protein carbonylation and alanine amino transferase (ALT). In the control PTENf/f animals, ethanol significantly increased ALT, liver triglycerides and steatosis. In contrast, chronic ethanol consumption in PTENLKO mice decreased hepatocellular damage when compared to PTENLKO pair-fed controls. Consumption of ethanol elevated protein carbonylation in PTENf/f animals but had no effect in PTENLKO animals. In PTENLKO mice, overall hepatic mRNA expression of genes that contribute to GSH homeostasis as well as reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations were significantly elevated compared to respective PTENf/f counterparts. These data indicate that during conditions of constitutive Akt activation and steatosis, increased GSH homeostasis assists in mitigation of ethanol-dependent induction of oxidative stress and hepatocellular damage. Furthermore, data herein suggest a divergence in EtOH-induced hepatocellular damage and increases in steatosis due to polyunsaturated fatty acids downstream of PTEN. PMID:27124661

  3. Liver-Specific Deletion of Phosphatase and Tensin Homolog Deleted on Chromosome 10 Significantly Ameliorates Chronic EtOH-Induced Increases in Hepatocellular Damage

    PubMed Central

    Orlicky, David J.; McCullough, Rebecca L.; Jiang, Hua; Maclean, Kenneth N.; Mercer, Kelly E.; Stiles, Bangyan L.; Saba, Laura M.; Ronis, Martin J.; Petersen, Dennis R.

    2016-01-01

    Alcoholic liver disease is a significant contributor to global liver failure. In murine models, chronic ethanol consumption dysregulates PTEN/Akt signaling. Hepatospecific deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTENLKO) mice possess constitutive activation of Akt(s) and increased de novo lipogenesis resulting in increased hepatocellular steatosis. This makes PTENLKO a viable model to examine the effects of ethanol in an environment of preexisting steatosis. The aim of this study was to determine the impact of chronic ethanol consumption and the absence of PTEN (PTENLKO) compared to Alb-Cre control mice (PTENf/f) on hepatocellular damage as evidenced by changes in lipid accumulation, protein carbonylation and alanine amino transferase (ALT). In the control PTENf/f animals, ethanol significantly increased ALT, liver triglycerides and steatosis. In contrast, chronic ethanol consumption in PTENLKO mice decreased hepatocellular damage when compared to PTENLKO pair-fed controls. Consumption of ethanol elevated protein carbonylation in PTENf/f animals but had no effect in PTENLKO animals. In PTENLKO mice, overall hepatic mRNA expression of genes that contribute to GSH homeostasis as well as reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations were significantly elevated compared to respective PTENf/f counterparts. These data indicate that during conditions of constitutive Akt activation and steatosis, increased GSH homeostasis assists in mitigation of ethanol-dependent induction of oxidative stress and hepatocellular damage. Furthermore, data herein suggest a divergence in EtOH-induced hepatocellular damage and increases in steatosis due to polyunsaturated fatty acids downstream of PTEN. PMID:27124661

  4. PARC/CCL18 Is a Plasma CC Chemokine with Increased Levels in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Struyf, Sofie; Schutyser, Evemie; Gouwy, Mieke; Gijsbers, Klara; Proost, Paul; Benoit, Yves; Opdenakker, Ghislain; Van Damme, Jo; Laureys, Geneviève

    2003-01-01

    Chemokines play an important role in leukocyte mobilization, hematopoiesis, and angiogenesis. Tissue-specific expression of particular chemokines also influences tumor growth and metastasis. Here, the CC chemokine pulmonary and activation-regulated chemokine (PARC)/CCL18 was measured in pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Surprisingly, PARC immunoreactivity was consistently detected in plasma from healthy donors. After purification to homogeneity, the presence of intact PARC (1–69) and processed PARC (1–68) in normal human plasma was confirmed by sequence and mass spectrometry analysis. Furthermore, PARC serum levels were significantly increased in children with T-ALL and prepreB-ALL compared to control serum samples, whereas serum levels in AML and preB-ALL patients were not significantly different from controls. In contrast, the hemofiltrate CC chemokine-1 (HCC-1)/CCL14 was not found to be a biomarker in any of these patients’ strata, whereas the cytokine interleukin-6 (IL-6) was significantly decreased in AML and prepreB-ALL. Stimulated leukocytic cell lines or lymphoblasts from patients produced IL-8/CXCL8 or macrophage inflammatory protein-1α (MIP-1α/CCL3) but not PARC, not even after IL-4 or IL-10 treatment. However, PARC was produced by superantigen or IL-4 stimulated monocytes co-cultured with lymphocytes or lymphoblastic cells. Serum PARC levels thus constitute a novel leukemia marker, possibly reflecting tumor/host cell interactions in the circulation. PMID:14578205

  5. Increased miR-16 expression induced by hepatitis C virus infection promotes liver fibrosis through downregulation of hepatocyte growth factor and Smad7.

    PubMed

    Zhu, Bin; Wei, Xiao-Xia; Wang, Tian-Bao; Zhou, Yan-Cai; Liu, A-Min; Zhang, Guang-Wen

    2015-08-01

    Hepatitis C virus (HCV) is involved in the initiation and progression of liver fibrosis by regulating genes encoding host proteins. However, the underlying mechanism of HCV-induced liver fibrosis is still to be determined. Reverse transcription polymerase chain reaction (RT-PCR) and western blot were performed to investigate the effect of HCV infection on the expression of the cellular microRNA miR-16 and its target genes encoding hepatocyte growth factor (HGF) and Smad7 in patients infected with HCV and in a liver cell line, QSG-7701, transfected with Ad-HCV, a recombinant adenovirus construct for expression of the HCV core protein. Regulation of HGF and Smad7 expression by miR-16 was assessed using luciferase reporter construct assays and miR-16 mimic transfection. Interferon-α (IFN-α) was used to verify the alteration of gene expression induced by HCV in QSG-7701 cells. Here, we found that miR-16 levels were increased in patients with HCV infection and were correlated with HGF and Smad7 expression levels in patients with HCV infection. Furthermore, HGF and Smad7 were predicted by bioinformatics analysis to be targets of miR-16. Upregulation of miR-16 and decreased HGF and Smad7 expression were still shown in QSG-7701 cells infected with Ad-HCV. Additionally, interferon-α (IFN-α) could reverse the changes in gene expression induced by HCV infection. These results suggest that the upregulation of miR-16 expression induced by HCV infection is a novel mechanism that contributes to downregulation of HGF and Smad7 in the development of liver fibrosis. PMID:26071245

  6. Liver (Hepatocellular) Cancer Prevention

    MedlinePlus

    ... Liver cancer is not common in the United States. Liver cancer is the fourth most common cancer and the third leading cause of cancer death in the world. In the United States, men, especially Chinese American men, have an increased ...

  7. Fatty liver accompanies an increase in lactobacillus species in the hind gut of C57BL/6 mice fed a high-fat diet.

    PubMed

    Zeng, Huawei; Liu, Jun; Jackson, Matthew I; Zhao, Feng-Qi; Yan, Lin; Combs, Gerald F

    2013-05-01

    High-fat (HF) diets can produce obesity and have been linked to the development of nonalcoholic fatty liver disease and changes in the gut microbiome. To test the hypothesis that HF feeding increases certain predominant hind gut bacteria and development of steatohepatitis, C57BL/6 mice were fed an HF (45% energy) or low-fat (LF) (10% energy) diet for 10 wk. At the end of the feeding period, body weights in the HF group were 34% greater than those in the LF group (P < 0.05). These changes were associated with dramatic increases in lipid droplet number and size, inflammatory cell infiltration, and inducible nitric oxide (NO) synthase protein concentration in the livers of mice fed the HF diet. Consistent with the fatty liver phenotype, plasma leptin and tumor necrosis factor-α concentrations were also elevated in mice fed the HF diet, indicative of chronic inflammation. Eight of 12 pairs of polymerase chain reaction (PCR) primers for bacterial species that typically predominate hind gut microbial ecology generated specific PCR products from the fecal DNA samples. The amount of DNA from Lactobacillus gasseri and/or Lactobacillus taiwanensis in the HF group was 6900-fold greater than that in the LF group. Many of these bacteria are bile acid resistant and are capable of bile acid deconjugation. Because bile acids are regulators of hepatic lipid metabolism, the marked increase of gut L. gasseri and/or L. taiwanensis species bacteria with HF feeding may play a role in development of steatohepatitis in this model. PMID:23486979

  8. The UDP-glucuronosyltransferase (UGT) 1A polymorphism c.2042C>G (rs8330) is associated with increased human liver acetaminophen glucuronidation, increased UGT1A exon 5a/5b splice variant mRNA ratio, and decreased risk of unintentional acetaminophen-induced acute liver failure.

    PubMed

    Court, Michael H; Freytsis, Marina; Wang, Xueding; Peter, Inga; Guillemette, Chantal; Hazarika, Suwagmani; Duan, Su X; Greenblatt, David J; Lee, William M

    2013-05-01

    Acetaminophen is cleared primarily by hepatic glucuronidation. Polymorphisms in genes encoding the acetaminophen UDP-glucuronosyltransferase (UGT) enzymes could explain interindividual variability in acetaminophen glucuronidation and variable risk for liver injury after acetaminophen overdose. In this study, human liver bank samples were phenotyped for acetaminophen glucuronidation activity and genotyped for the major acetaminophen-glucuronidating enzymes (UGTs 1A1, 1A6, 1A9, and 2B15). Of these, only three linked single nucleotide polymorphisms (SNPs) located in the shared UGT1A-3'UTR region (rs10929303, rs1042640, rs8330) were associated with acetaminophen glucuronidation activity, with rs8330 consistently showing higher acetaminophen glucuronidation at all the tested concentrations of acetaminophen. Mechanistic studies using luciferase-UGT1A-3'UTR reporters indicated that these SNPs do not alter mRNA stability or translation efficiency. However, there was evidence for allelic imbalance and a gene-dose proportional increase in the amount of exon 5a versus exon 5b containing UGT1A mRNA spliced transcripts in livers with the rs8330 variant allele. Cotransfection studies demonstrated an inhibitory effect of exon 5b containing cDNAs on acetaminophen glucuronidation by UGT1A1 and UGT1A6 cDNAs containing exon 5a. In silico analysis predicted that rs8330 creates an exon splice enhancer site that could favor exon 5a (over exon 5b) utilization during splicing. Finally, the prevalence of rs8330 was significantly lower (P = 0.027, χ(2) test) in patients who had acute liver failure from unintentional acetaminophen overdose compared with patients with acute liver failure from other causes or a race- or ethnicity-matched population. Together, these findings suggest that rs8330 is an important determinant of acetaminophen glucuronidation and could affect an individual's risk for acetaminophen-induced liver injury. PMID:23408116

  9. Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss

    PubMed Central

    Schmitz, J.; Evers, N.; Awazawa, M.; Nicholls, H.T.; Brönneke, H.S.; Dietrich, A.; Mauer, J.; Blüher, M.; Brüning, J.C.

    2016-01-01

    Objective Obesity represents a major risk factor for the development of type 2 diabetes mellitus, atherosclerosis and certain cancer entities. Treatment of obesity is hindered by the long-term maintenance of initially reduced body weight, and it remains unclear whether all pathologies associated with obesity are fully reversible even upon successfully maintained weight loss. Methods We compared high fat diet-fed, weight reduced and lean mice in terms of body weight development, adipose tissue and liver insulin sensitivity as well as inflammatory gene expression. Moreover, we assessed similar parameters in a human cohort before and after bariatric surgery. Results Compared to lean animals, mice that demonstrated successful weight reduction showed increased weight gain following exposure to ad libitum control diet. However, pair-feeding weight-reduced mice with lean controls efficiently stabilized body weight, indicating that hyperphagia was the predominant cause for the observed weight regain. Additionally, whereas glucose tolerance improved rapidly after weight loss, systemic insulin resistance was retained and ameliorated only upon prolonged pair-feeding. Weight loss enhanced insulin action and resolved pro-inflammatory gene expression exclusively in the liver, whereas visceral adipose tissue displayed no significant improvement of metabolic and inflammatory parameters compared to obese mice. Similarly, bariatric surgery in humans (n = 55) resulted in massive weight reduction, improved hepatic inflammation and systemic glucose homeostasis, while adipose tissue inflammation remained unaffected and adipocyte-autonomous insulin action only exhibit minor improvements in a subgroup of patients (42%). Conclusions These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue

  10. Adenosine triphosphate infusion increases liver energy status in advanced lung cancer patients: an in vivo 31P magnetic resonance spectroscopy study.

    PubMed

    Leij-Halfwerk, Susanne; Agteresch, Hendrik J; Sijens, Paul E; Dagnelie, Pieter C

    2002-02-01

    We recently observed inhibition of weight loss in patients with advanced nonsmall-cell lung cancer after intravenous infusion of ATP. Because liver ATP levels were found to be decreased in lung cancer patients with weight loss, the present 31P magnetic resonance spectroscopy (MRS) study was aimed at investigating whether ATP infusion restores liver energy status in these patients. Nine patients with advanced nonsmall-cell lung cancer (stage IIIB/IV) were studied 1 week before (baseline) and at 22 to 24 hours of continuous ATP infusion (37-75 microg/kg/min). Localized hepatic 31P MR spectra (repetition time 15 seconds), obtained in the overnight-fasted state, were analyzed for ATP and P(i) content. Ten healthy subjects (without ATP infusion) served as control. Liver ATP levels in lung cancer patients increased from 8.8 +/- 0.7% (relative to total MR-detectable phosphate; mean +/- SE) at baseline to 12.2 +/- 0.9% during ATP infusion (P <.05), i.e., a level similar to that in healthy subjects (11.9 +/- 0.9%). The increase in ATP level during ATP infusion was most prominent in patients with > or = 5% weight loss (baseline: 7.9 +/- 0.7%, during ATP infusion: 12.8 +/- 1.0%, P < 0.01). In conclusion, ATP infusion restores hepatic energy levels in patients with advanced lung cancer, especially in weight-losing patients. These changes may contribute to the previously reported beneficial effects of ATP infusion on the nutritional status of lung cancer patients. PMID:11826418

  11. Prevalence of fatty liver in non-obese Japanese children with atopic dermatitis.

    PubMed

    Kimata, Hajime

    2005-06-01

    Fatty liver in non-obese Japanese children was observed in 3.2% of non-atopic children and in 17.6% of patients with atopic dermatitis in 2000. The prevalence of fatty liver in non-obese children aged 0-12 years was studied from 2001 to 2003. Subjects were either non-atopic children, or suffering from bronchial asthma, allergic rhinitis, or atopic dermatitis. Fatty liver was studied by abdominal ultrasound scans. The prevalence of fatty liver was increasing annually, and it reached to 12.5% in non-atopic children, 13.1% in patients with bronchial asthma, 13.7% in patients with allergic rhinitis, or 33.9% in patients with atopic dermatitis, in 2003. Since fatty liver in childhood may be a risk factor for lifestyle-related diseases in future, care should be taken to prevent it. PMID:15995275

  12. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  13. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  14. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  15. Increasing the HIFU ablation rate through an MRI-guided sonication strategy using shock waves: feasibility in the in vivo porcine liver

    NASA Astrophysics Data System (ADS)

    Ramaekers, P.; de Greef, M.; van Breugel, J. M. M.; Moonen, C. T. W.; Ries, M.

    2016-02-01

    This study investigated whether an MR-guided pulsed HIFU ablation strategy could be implemented under clinical conditions, using a transducer designed for uterine fibroid ablation, to obtain an ablation rate that is sufficiently high for clinical abdominal HIFU therapy in highly perfused organs. A pulsed HIFU ablation strategy, aimed at increasing the energy absorption in the HIFU focal area by local shock wave formation in the non-linear pressure regime, was compared to an energy-equivalent continuous wave sonication strategy in the linear pressure regime. Both ablation strategies were used for transcutaneous sonication of pre-defined treatment cells in the livers of 5 pigs in vivo. Temperature evolution in both the target area as well as the pre-focal muscle layer was monitored simultaneously using MR thermometry. Local energy absorption and thermal dose volumes were shown to be increased using the pulsed ablation strategy, while preserving healthy tissue in the near field of the acoustic beam. Respiratory motion compensation of both acoustic energy delivery and MR thermometry was applied through gating based on MR navigator echoes. Histopathology showed that confluent vacuolated thermal lesions were created when the pulsed ablation strategy was used. Additionally, it was shown that the heat sink effect caused by the presence of larger vessels could be overcome. The pulsed HIFU ablation strategy achieved an ablation rate of approximately 4 ml per hour in the in vivo porcine liver, without causing undesired damage to healthy tissues in the near field.

  16. Increasing the HIFU ablation rate through an MRI-guided sonication strategy using shock waves: feasibility in the in vivo porcine liver.

    PubMed

    Ramaekers, P; de Greef, M; van Breugel, J M M; Moonen, C T W; Ries, M

    2016-02-01

    This study investigated whether an MR-guided pulsed HIFU ablation strategy could be implemented under clinical conditions, using a transducer designed for uterine fibroid ablation, to obtain an ablation rate that is sufficiently high for clinical abdominal HIFU therapy in highly perfused organs. A pulsed HIFU ablation strategy, aimed at increasing the energy absorption in the HIFU focal area by local shock wave formation in the non-linear pressure regime, was compared to an energy-equivalent continuous wave sonication strategy in the linear pressure regime. Both ablation strategies were used for transcutaneous sonication of pre-defined treatment cells in the livers of 5 pigs in vivo. Temperature evolution in both the target area as well as the pre-focal muscle layer was monitored simultaneously using MR thermometry. Local energy absorption and thermal dose volumes were shown to be increased using the pulsed ablation strategy, while preserving healthy tissue in the near field of the acoustic beam. Respiratory motion compensation of both acoustic energy delivery and MR thermometry was applied through gating based on MR navigator echoes. Histopathology showed that confluent vacuolated thermal lesions were created when the pulsed ablation strategy was used. Additionally, it was shown that the heat sink effect caused by the presence of larger vessels could be overcome. The pulsed HIFU ablation strategy achieved an ablation rate of approximately 4 ml per hour in the in vivo porcine liver, without causing undesired damage to healthy tissues in the near field. PMID:26757987

  17. Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1

    PubMed Central

    Kumsta, R; Marzi, S J; Viana, J; Dempster, E L; Crawford, B; Rutter, M; Mill, J; Sonuga-Barke, E J S

    2016-01-01

    Exposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. Although the mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied the impact of severe early-life adversity on epigenetic variation in a sample of adolescents adopted from the severely depriving orphanages of the Romanian communist era in the 1980s. We quantified buccal cell DNA methylation at ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6–43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=16) not exposed to severe deprivation. Although no probe-wise differences remained significant after controlling for the number of probes tested, we identified an exposure-associated differentially methylated region (DMR) spanning nine sequential CpG sites in the promoter-regulatory region of the cytochrome P450 2E1 gene (CYP2E1) on chromosome 10 (corrected P=2.98 × 10−5). Elevated DNA methylation across this region was also associated with deprivation-related clinical markers of impaired social cognition. Our data suggest that environmental insults of sufficient biological impact during early development are associated with long-lasting epigenetic changes, potentially reflecting a biological mechanism linking the effects of early-life adversity to cognitive and neurobiological phenotypes. PMID:27271856

  18. Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1.

    PubMed

    Kumsta, R; Marzi, S J; Viana, J; Dempster, E L; Crawford, B; Rutter, M; Mill, J; Sonuga-Barke, E J S

    2016-01-01

    Exposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. Although the mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied the impact of severe early-life adversity on epigenetic variation in a sample of adolescents adopted from the severely depriving orphanages of the Romanian communist era in the 1980s. We quantified buccal cell DNA methylation at ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6-43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=16) not exposed to severe deprivation. Although no probe-wise differences remained significant after controlling for the number of probes tested, we identified an exposure-associated differentially methylated region (DMR) spanning nine sequential CpG sites in the promoter-regulatory region of the cytochrome P450 2E1 gene (CYP2E1) on chromosome 10 (corrected P=2.98 × 10(-5)). Elevated DNA methylation across this region was also associated with deprivation-related clinical markers of impaired social cognition. Our data suggest that environmental insults of sufficient biological impact during early development are associated with long-lasting epigenetic changes, potentially reflecting a biological mechanism linking the effects of early-life adversity to cognitive and neurobiological phenotypes. PMID:27271856

  19. Upregulated Expression of A20 on Monocytes is Associated With Increased Severity of Acute-on-Chronic Hepatitis B Liver Failure: A Case-Control Study.

    PubMed

    Guo, Yonghong; He, Yu; Zhang, Ying; Zhou, Yun; Qin, Yuan; Fan, Chao; Ji, Guangxi; Zhang, Peixin; Jia, Zhansheng

    2015-09-01

    A20 expression is increased in various inflammatory diseases. However, the role of A20 in acute-on-chronic liver failure is unknown. This study was to evaluate A20 expression on monocytes and its associations with the severity of acute-on-chronic hepatitis B liver failure (ACHBLF). Thirty-seven patients with ACHBLF, 20 patients with chronic hepatitis B (CHB), and 15 healthy controls (HC) were enrolled in this case-control study. A20-positive monocytes were identified using flow cytometry. Serum levels of interleukin (IL)-10, IL-12p70, and TNF-α were determined using bead cytometry. A20 and IL-10 expressions were examined in THP-1 cells stimulated by lipopolysaccharide (LPS). The frequency of A20+ monocytes was significantly increased in patients with ACHBLF compared with HC (median [interquartile range, IQR]: 15.7 [22.8]% vs 2.5 [4.7]%, P < 0.001). Increased monocyte A20 expression was detected during the progression phase (including the mild/moderate and severe grades of ACHBLF) compared with patients in the recovery phase (both P < 0.05), and in the ACHBLF worsening group compared with patients in the improvement group (P < 0.001). LPS treatment upregulated A20 and IL-10 expressions in THP-1 cells. A20 expression on monocytes from patients with ACHBLF was positively correlated with total bilirubin (r = 0.60, P = 0.0001), direct bilirubin (r = 0.63, P < 0.0001), and MELD score (r = 0.43, P = 0.008), and inversely with prothrombin activity (r = -0.33, P = 0.046). IL-10 and TLR4 expression levels in monocytes, and serum levels of IL-10, IL-12p70, and TNF-α were increased in patients with ACHBLF compared with patients with CHB and HC. Increased A20 expression on monocytes was associated with the severity of ACHBLF. PMID:26426612

  20. The subcellular location, maturation and response to increased plasma glucagon of Ruthenium Red-insensitive calcium-ion transport in rat liver

    PubMed Central

    Bygrave, Fyfe L.; Tranter, Charmaine J.

    1978-01-01

    1. The subcellular distribution and maturation of Ruthenium Red-insensitive Ca2+ transport activity were determined in livers of rats ranging in age from 3 days pre-term to 10 weeks of adult life and compared with those of glucose 6-phosphatase, 5′-nucleotidase and Ruthenium Red-sensitive Ca2+ transport. Initial rates of Ruthenium Red-insensitive Ca2+ transport were highest in those fractions enriched in glucose 6-phosphatase, i.e. the microsomal fraction; this fraction was devoid of Ruthenium Red-sensitive Ca2+ transport activity. Although the heaviest fraction (nuclear) contained significant amounts of 5′-nucleotidase activity it was devoid of Ruthenium Red-insensitive Ca2+ transport activity. 2. Foetal rat liver contain minimal amounts of Ruthenium Red-insensitive Ca2+ transport activity, glucose 6-phosphatase and 5′-nucleotidase activities. These begin to be expressed concomitantly soon after birth; Ruthenium Red-insensitive Ca2+ transport is maximal by 3 to 4 days and remains so for up to at least 10 weeks of adult life. Glucose 6-phosphatase also reaches a peak at 3–4 days, but then rapidly decreases to approach adult values. Maximal activity of 5′-nucleotidase in the microsomal and nuclear fractions is seen about 4–6 days after birth; this enzyme activity remains increased for up to about 10 days and then falls, but not as rapidly as glucose 6-phosphatase. It is tentatively suggested that the bulk of the Ruthenium Red-insensitive Ca2+ transport is attributable to the system derived from the endoplasmic reticulum. 3. Administration of glucagon to adult rats enhances by 2–3-fold the initial rate of Ruthenium Red-insensitive Ca2+ transport in the intermediate but not the microsomal fraction. The hormone-induced effect is fully suppressed by co-administration of puromycin, is dose-dependent with half-maximal response at approx. 1μg of glucagon/100g body wt. and time-dependent exhibiting a half-maximal response about 1h after administration of the

  1. Liver angioscintigraphy: clinical applications.

    PubMed

    Dragoteanu, Mircea; Cotul, Sabin O; Pîgleşan, Cecilia; Tamaş, Stefan

    2004-03-01

    Liver angioscintigraphy (LAS) is a radio-isotope method for the investigation of liver perfusion and its alteration in various hepatic diseases. It measures the arterial and portal venous fractions of total liver blood flow. The percentage of liver blood flow supplied by hepatic artery is estimated mathematically by the hepatic perfusion index (HPI), normally between 25 % and 40 %. The decrease of portal blood flow in liver cirrhosis is compensated ("buffer" mechanisms) by increased arterial supply, with higher HPI value. For a patient with chronic liver disease, HPI over 50% suggests arterialization of hepatic perfusion, guiding the diagnose to liver cirrhosis. Splenic curve is completing the diagnostic information of the hepatic curve. Corroborated with per rectal scintigraphy and liver SPECT, LAS offers a good hemodynamic staging of chronic inflammatory liver diseases. Malignant tumors (primitive or metastases) increase the arterial supply of the liver and decrease the portal flow, HPI being over 50% (currently 65 % - 90 %). Benign tumors do not change portal/arterial liver blood flow ratio. SPECT or non-scintigraphic morphological investigations increase the diagnostic value of LAS for primitive liver tumors. Liver cancer occurring on cirrhosis is a limitative factor for LAS. Hepatic metastases increase the arterial perfusion (and HPI value) very quickly, before their size allows morphologic imaging diagnosis. LAS is therefore an early method to diagnose liver metastases being especially used in colorectal cancer. Other clinical applications of LAS are: follow up of liver toxicity of drugs, evaluation of portal vein permeability, post surgery follow up of the liver tumor patients. PMID:15054528

  2. Liver Facts

    MedlinePlus

    ... Home / Before The Transplant / Organ Facts / Liver Organ Facts Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver ... Receiving "the call" About the Operation Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Facts How the Liver Works The liver is one ...

  3. Increased anaplerosis, TCA cycling, and oxidative phosphorylation in the liver of dairy cows with intensive body fat mobilization during early lactation.

    PubMed

    Schäff, Christine; Börner, Sabina; Hacke, Sandra; Kautzsch, Ulrike; Albrecht, Dirk; Hammon, Harald M; Röntgen, Monika; Kuhla, Björn

    2012-11-01

    The onset of milk production lets mammals experience an enormous energy and nutrient demand. To meet these requirements, high-yielding dairy cows mobilize body fat resulting in an augmented hepatic oxidative metabolism, which has been suggested to signal for depressing hunger after calving. To examine how the extent of fat mobilization influences hepatic oxidative metabolism and thus potentially feed intake, blood and liver samples of 19 Holstein cows were taken throughout the periparturient period. Retrospectively grouped according to high (H) and low (L) liver fat content, H cows showed higher fatty acid but lower amino acid plasma concentrations and lower feed intake than L cows. The hepatic phospho-AMPK/total AMP ratio was not different between groups but decreased after parturition. A 2-DE coupled MALDI-TOF-TOF analysis and qRT-PCR studies revealed H cows having lower expressions of major enzymes involved in mitochondrial β-oxidation, urea cycling, and the pentose phosphate pathway but higher expressions of enzymes participating in peroxisomal and endoplasmic fatty acid degradation, pyruvate and TCA cycling, amino acid catabolism, oxidative phosphorylation, and oxidative stress defense. These data indicate that increasing lipolysis leads to augmenting nutrient catabolism for anaplerosis and mitochondrial respiration, providing a molecular link between hepatic oxidative processes and feed intake. PMID:23046364

  4. Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

    PubMed

    Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

    2012-11-30

    Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. PMID:23085348

  5. Increased Susceptibility of Gracilinanus microtarsus Liver Mitochondria to Ca2+-Induced Permeability Transition Is Associated with a More Oxidized State of NAD(P)

    PubMed Central

    Ronchi, Juliana A.; Henning, Barbara; Ravagnani, Felipe G.; Figueira, Tiago R.; Castilho, Roger F.; dos Reis, Sergio F.; Vercesi, Anibal E.

    2015-01-01

    In addition to be the cell's powerhouse, mitochondria also contain a cell death machinery that includes highly regulated processes such as the membrane permeability transition pore (PTP) and reactive oxygen species (ROS) production. In this context, the results presented here provide evidence that liver mitochondria isolated from Gracilinanus microtarsus, a small and short life span (one year) marsupial, when compared to mice, are much more susceptible to PTP opening in association with a poor NADPH dependent antioxidant capacity. Liver mitochondria isolated from the marsupial are well coupled and take up Ca2+ but exhibited a much lower Ca2+ retention capacity than mouse mitochondria. Although the known PTP inhibitors cyclosporin A, ADP, and ATP significantly increased the marsupial mitochondria capacity to retain Ca2+, their effects were much larger in mice than in marsupial mitochondria. Both fluorescence and HPLC analysis of mitochondrial nicotinamide nucleotides showed that both content and state of reduction (mainly of NADPH) were lower in the marsupial mitochondria than in mice mitochondria despite the similarity in the activity of the glutathione peroxidase/reductase system. Overall, these data suggest that PTP opening is an important event in processes of Ca2+ signalling to cell death mediated by mitochondrial redox imbalance in G. microtarsus. PMID:26583063

  6. Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study.

    PubMed

    Eyster, M E; Fried, M W; Di Bisceglie, A M; Goedert, J J

    1994-08-15

    We have previously observed an increased frequency of liver failure in human immunodeficiency virus (HIV)-infected hemophiliacs. The purpose of this study was to quantitate hepatitis C virus (HCV) RNA levels in serial samples from HIV-seropositive (HIV+) and HIV-seronegative (HIV-) hemophiliacs before and after HIV seroconversion, and to examine the relationship of HCV RNA levels to CD4 cell counts and to hepatic dysfunction over time. HCV RNA levels were measured on serial samples of serum stored frozen from 17 HCV+/HIV+ and 17 HCV+/HIV- subjects matched within 5 years of their birth dates. All were HCV+ before study entry. HCV RNA levels were quantitated by a branched DNA-enhanced label amplification (bDNA) assay. For samples less than the cut off, HCV RNA was measured by the nested polymerase chain reaction. Individual changes over time, clinical groups, and mean values within predetermined time windows were compared with Wilcoxon rank sum tests. Mean HCV RNA levels increased from 2.76 (standard error [SE] 1.33) x 10(5) to 2.84 (SE 1.39) x 10(6) eq/mL during the first 2 years after HIV seroconversion (P = .006). Baseline HCV RNA levels in the pre-HIV seroconversion group were not significantly different from the baseline levels in those who remained HIV (P = .79). Over the entire period of study, HCV RNA levels increased nearly threefold in those who remained HIV- (mean 9.47 [SE 4.78] x 10(5) to 2.81 [SE 1.13] x 10(6)/mL; P = .02). Among those who became HIV+, HCV RNA levels increased 58-fold (mean 2.85 [SE 1.26] x 10(5) to 1.66 [SE 0.57] x 10(7) eq/mL; P = .0001). The rate of increase in HCV RNA levels was eightfold faster for HIV+ subjects than for subjects who remained HIV- (P = .009). HCV RNA levels increased twofold higher in 5 subjects who developed liver failure compared with the 12 who did not (P = .43). HCV RNA levels correlated significantly with CD4 counts (R = -.33, P = .01) and serum aspartate aminotransferase levels (AST) (R = .36, P = .007). We

  7. Thyroid-Stimulating Hormone Increases HNF-4α Phosphorylation via cAMP/PKA Pathway in the Liver

    PubMed Central

    Song, Yongfeng; Zheng, Dongmei; Zhao, Meng; Qin, Yejun; Wang, Tingting; Xing, Wanjia; Gao, Ling; Zhao, Jiajun

    2015-01-01

    Hepatocyte nuclear factor-4 alpha (HNF-4α) is an orphan nuclear receptor with important roles in hepatic metabolism. Protein phosphorylation plays a functional role in its nuclear localization, DNA binding, and transactivation. Thyroid-stimulating hormone (TSH) is a hormone produced by the anterior pituitary gland, whose direct effect on the metabolic pathway has been observed. Our previous study demonstrated that TSH significantly decreases hepatic nuclear HNF-4α expression. However, whether TSH can influence HNF-4α phosphorylation is unclear. Here, we discovered that TSH can increase HNF-4α phosphorylation and modulate its subcellularlocalization. When HepG2 cells were treated with TSH, the phosphorylation of HNF-4α increased and its nuclear localization was interrupted. Cytoplasmic HNF-4α increased, while nuclear HNF-4α decreased. When the cAMP/PKA pathway was inhibited by the PKA inhibitor H89 and the adenylate cyclase (AC) inhibitor SQ22536, the TSH-mediated phosphorylation of HNF-4α was disrupted. When Tshr was silenced in mice, the phosphorylation of HNF-4α decreased, and cytoplasmic HNF-4α decreased while nuclear HNF-4α increased. In conclusion, our study revealed a novel mechanism by which TSH regulated the hepatic HNF-4α subcellular localization, suggesting the possibility that one of the effects of TSH is to reduce the expression of HNF-4α target genes. PMID:26302721

  8. Meta-analysis of Gene Expression in the Mouse Liver Reveals Biomarkers Associated with Inflammation Increased Early During Aging

    EPA Science Inventory

    Aging is associated with a predictable loss of cellular homeostasis, a decline in physiological function and an increase in various diseases. We hypothesized that similar age-related gene expression profiles would be observed in mice across independent studies. Employing a metaan...

  9. Maneb disturbs expression of superoxide dismutase and glutathione peroxidase, increases reactive oxygen species production, and induces genotoxicity in liver of adult mice.

    PubMed

    Ben Amara, Ibtissem; Ben Saad, Hajer; Hamdaoui, Latifa; Karray, Aida; Boudawara, Tahia; Ben Ali, Yassine; Zeghal, Najiba

    2015-08-01

    Maneb (MB), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. However there is a lack of informations regarding the risks arising from MB exposure on non target organisms, especially mammals. The aim of this study was to investigate the morphological, biochemical and molecular aspects of liver injury after exposure of mice to MB. Four doses of MB corresponding to 1/8 (group D1), 1/6 (group D2), 1/4 (group D3), and 1/2 (group D4) of lethal dose (DL50 = 1500 mg/kg body weight) were administered to adult mice. Oxidative stress parameters were also objectified by molecular and histological endpoints in the liver. Maneb caused hepatotoxicity as characterized by the significant increase in the levels of malondialdehyde and protein oxidation marker, advanced oxidation protein products (AOPP). The activities of catalase, glutathione peroxidase, superoxide dismutase and the levels of glutathione decreased significantly in all treated mice, while vitamin C levels decreased only in group D4. We also noted a significant decrease in gene expression of superoxide dismutase and glutathione peroxidase enzymes. Maneb caused nucleic acids degradation testifying its genotoxicity. Yet, biochemical markers in plasma showed a decrease in total protein and an increase in aspartate, alanine amino transferases and bilirubin levels in all treatment groups. Moreover, plasma levels of cholesterol, triglycerides and low density lipoprotein-cholesterol significantly increased, while those of high density lipoprotein-cholesterol decreased. These biochemical alterations were correlated with significantly histological changes. Our data showed, for the first time, that intraperitoneal injection of very high non environmentally relevant MB concentrations to adult mice resulted in oxidative stress leading to hepatotoxicity and the impairment of defense systems, confirming the

  10. Markets and Childhood Obesity Policy

    ERIC Educational Resources Information Center

    Cawley, John

    2006-01-01

    In examining the childhood obesity epidemic from the perspective of economics, John Cawley looks at both possible causes and possible policy solutions that work through markets. The operation of markets, says Cawley, has contributed to the recent increase in childhood overweight in three main ways. First, the real price of food fell. In…

  11. Childhood Victimization and Lifetime Revictimization

    ERIC Educational Resources Information Center

    Widom, Cathy Spatz; Czaja, Sally J.; Dutton, Mary Ann

    2008-01-01

    Objective: To examine the fundamental hypothesis that childhood victimization leads to increased vulnerability for subsequent (re)victimization in adolescence and adulthood and, if so, whether there are differences in rates of experiencing traumas and victimizations by gender, race/ethnicity, and type of childhood abuse and/or neglect. Methods:…

  12. Managing childhood obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The prevalence of childhood obesity has steadily increased over the last decades, with approximately 35% of children aged 6-19 classified as overweight or obese. Recently, a plateau in the increasing rates of obesity has been observed. Despite this leveling off, overweight and obese children are hea...

  13. Increase in the ADP/ATP exchange in rat liver mitochondria irradiated in vitro by helium-neon laser

    SciTech Connect

    Passarella, S.; Ostuni, A.; Atlante, A.; Quagliariello, E.

    1988-10-31

    To gain some insight into the mechanism of cell photostimulation by laser light, measurements were made of the rate of ADP/ATP exchange in mitochondria irradiated with the low power continuous wave Helium Neon laser (energy dose 5 Joules/cm2). To do this a method has been developed to continuously monitor ATP efflux from phosphorylating mitochondria caused by externally added ADP, by photometrically following the NADP+ reduction which occurs in the presence of glucose, hexokinase, glucose-6-phosphate dehydrogenase and effluxed ATP. The NADP+ reduction rate shows hyperbolic dependence on ADP concentration (Km and Vmax values 8.5 +/- 0.87 microM and 20.7 +/- 0.49 nmoles NADP+ reduced/min x mg mitochondrial protein, respectively), and proves to measure the activity of the ADP/ATP translocator as shown by inhibition experiments using atracyloside, powerful inhibitor of this carrier. Irradiation was found to enhance the rate of ADP/ATP antiport, with externally added ADP ranging between 5 and 100 microM. As a result of experiments carried out with mitochondria loaded with either ATP or ADP, the increase in the activity of the ADP/ATP translocator is here proposed to depend on the increase in the electrochemical proton gradient which occurs owing to irradiation of mitochondria.

  14. High-Fat Diet Reduces the Formation of Butyrate, but Increases Succinate, Inflammation, Liver Fat and Cholesterol in Rats, while Dietary Fibre Counteracts These Effects

    PubMed Central

    Jakobsdottir, Greta; Xu, Jie; Molin, Göran; Ahrné, Siv; Nyman, Margareta

    2013-01-01

    Introduction Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs), particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation. Objective To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks. Material and Methods Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin – acetic acid; guar gum – propionic acid; or a mixture – butyric acid). At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks. Results and Discussion Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet. PMID:24236183

  15. Childhood Leukemia

    MedlinePlus

    Leukemia is cancer of the white blood cells. It is the most common type of childhood cancer. ... blood cells help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. ...

  16. Childhood Leukemia

    MedlinePlus

    ... acute types. Symptoms include Infections Fever Loss of appetite Tiredness Easy bruising or bleeding Swollen lymph nodes Night sweats Shortness of breath Pain in the bones or joints Risk factors for childhood leukemia include having a brother ...

  17. Rapamycin reverses age-related increases in mitochondrial ROS production at complex I, oxidative stress, accumulation of mtDNA fragments inside nuclear DNA, and lipofuscin level, and increases autophagy, in the liver of middle-aged mice.

    PubMed

    Martínez-Cisuelo, V; Gómez, J; García-Junceda, I; Naudí, A; Cabré, R; Mota-Martorell, N; López-Torres, M; González-Sánchez, M; Pamplona, R; Barja, G

    2016-10-01

    Rapamycin consistently increases longevity in mice although the mechanism of action of this drug is unknown. In the present investigation we studied the effect of rapamycin on mitochondrial oxidative stress at the same dose that is known to increase longevity in mice (14mgofrapamycin/kg of diet). Middle aged mice (16months old) showed significant age-related increases in mitochondrial ROS production at complex I, accumulation of mtDNA fragments inside nuclear DNA, mitochondrial protein lipoxidation, and lipofuscin accumulation compared to young animals (4months old) in the liver. After 7weeks of dietary treatment all those increases were totally or partially (lipofuscin) abolished by rapamycin, middle aged rapamycin-treated animals showing similar levels in those parameters to young animals. The decrease in mitochondrial ROS production was due to qualitative instead of quantitative changes in complex I. The decrease in mitochondrial protein lipoxidation was not due to decreases in the amount of highly oxidizable unsaturated fatty acids. Rapamycin also decreased the amount of RAPTOR (of mTOR complex) and increased the amounts of the PGC1-α and ATG13 proteins. The results are consistent with the possibility that rapamycin increases longevity in mice at least in part by lowering mitochondrial ROS production and increasing autophagy, decreasing the derived final forms of damage accumulated with age which are responsible for increased longevity. The decrease in lipofuscin accumulation induced by rapamycin adds to previous information suggesting that the increase in longevity induced by this drug can be due to a decrease in the rate of aging. PMID:27498120

  18. Migraine and lifestyle in childhood.

    PubMed

    Casucci, Gerardo; Villani, Veronica; d'Onofrio, Florindo; Russo, Antonio

    2015-05-01

    Migraine is one of the most frequently reported somatic complaints in childhood, with a negative impact on health-related quality of life. The incidence of migraine in childhood has substantially increased over the past 30 years, probably due to both increased awareness of the disease and lifestyle changes in this age group. Indeed, several conditions have been identified as risk factors for migraine in childhood. Amongst these, dysfunctional family situation, the regular consumption of alcohol, caffeine ingestion, low level of physical activity, physical or emotional abuse, bullying by peers, unfair treatment in school and insufficient leisure time seem to play a critical role. Nevertheless, there are only few studies about the association between migraine and lifestyle in childhood, due to previous observations specifically focused on "headache" in children. In this brief review, we will concentrate upon recent studies aimed to explore migraine and lifestyle risk factors in childhood. PMID:26017522

  19. Liver Wellness

    MedlinePlus

    ... to liver wellness. • There are more than 100 liver diseases. • Liver disease is one of the top 10 causes of ... out of every 10 Americans is affected by liver disease. • Some liver diseases such as hepatitis A, hepatitis ...

  20. PRKAR1A overexpression is associated with increased ECPKA autoantibody in liver fluke-associated cholangiocarcinoma: application for assessment of the risk group.

    PubMed

    Loilome, Watcharin; Yooyuen, Sasithorn; Namwat, Nisana; Sithithaworn, Paiboon; Puapairoj, Anucha; Kano, Junko; Noguchi, Masayuki; Miwa, Masanao; Yongvanit, Puangrat

    2012-12-01

    Cholangiocarcinoma (CCA) associated with Opisthorchis viverrini (Ov) chronic infection is the most frequent primary liver cancer in Thailand, and current approaches to early diagnosis and curative treatments are largely disappointing. We hypothesize a role for protein kinase A (PKA) in Ov-induced CCA. First, we studied the PKA isozyme switching in the liver from the hamster CCA model using quantitative (q) PCR, in situ hybridization, and immunohistochemical and western blot analysis. Second, the presence of extracellular PKA (ECPKA) in CCA cell lines and their conditioned media was demonstrated by western blot and PKA activity assay. Third, we determined the association between PRKAR1A expression and serum ECPKA autoantibody in patients with CCA by ELISA. We demonstrated that an increased PRKAR1A expression is restricted to the biliary cells starting from week 1, with remarkable up-regulation when CCA has completely developed by week 24. The switching of the PKA regulatory subunit isoforms from PRKAR2B/PKAII to PRKAR1A/PKAI is significantly associated with cholangiocyte proliferation. Further, we observed that human CCA cell lines express PRKAR1A but not PRKAR2B and excrete ECPKA. Finally, ECPKA autoantibodies are detected in serum of patients with CCA, adenocarcinoma, and Ov infection with periductal fibrosis, but not from Ov-infected subjects without periductal fibrosis lesion and healthy controls. We conclude that PKA isozyme switching and the PRKAR1A/PKAI pathway might contribute to the induction of cholangiocyte transformation and proliferation in Ov-induced CCA. Overexpression of PRKAR1A leads to secretion of ECPKA which is associated with serum autoantibody that may constitute a biomarker for human CCA genesis. PMID:22922884

  1. Dietary ɛ-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats

    PubMed Central

    Hosomi, Ryota; Yamamoto, Daiki; Otsuka, Ren; Nishiyama, Toshimasa; Yoshida, Munehiro; Fukunaga, Kenji

    2015-01-01

    ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

  2. Dietary ɛ-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats.

    PubMed

    Hosomi, Ryota; Yamamoto, Daiki; Otsuka, Ren; Nishiyama, Toshimasa; Yoshida, Munehiro; Fukunaga, Kenji

    2015-03-01

    ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

  3. Liver Transplant

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  4. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  5. Liver disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the liver ...

  6. Liver biopsy

    MedlinePlus

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  7. Fasting Plasma Insulin at 5 Years of Age Predicted Subsequent Weight Increase in Early Childhood over a 5-Year Period—The Da Qing Children Cohort Study

    PubMed Central

    Chen, Yan Yan; Wang, Jin Ping; Jiang, Ya Yun; Li, Hui; Hu, Ying Hua; Lee, Kok Onn; Li, Guang Wei

    2015-01-01

    Background The association between hyperinsulinemia and obesity is well known. However, it is uncertain especially in childhood obesity, if initial fasting hyperinsulinemia predicts obesity, or obesity leads to hyperinsulinemia through insulin resistance. Objective To investigate the predictive effect of fasting plasma insulin on subsequent weight change after a 5-year interval in childhood. Methods 424 Children from Da Qing city, China, were recruited at 5 years of age and followed up for 5 years. Blood pressure, anthropometric measurements, fasting plasma insulin, glucose and triglycerides were measured at baseline and 5 years later. Results Fasting plasma insulin at 5 years of age was significantly correlated with change of weight from 5 to 10 years (ΔWeight). Children in the lowest insulin quartile had ΔWeight of 13.08±0.73 kg compare to 18.39±0.86 in the highest insulin quartile (P<0.0001) in boys, and similarly 12.03±0.71 vs 15.80±0.60 kg (P<0.0001) in girls. Multivariate analysis showed that the predictive effect of insulin at 5 years of age on subsequent weight gain over 5 years remained statistically significant even after the adjustment for age, sex, birth weight, TV-viewing time and weight (or body mass index) at baseline. By contrast, the initial weight at 5 years of age did not predict subsequent changes in insulin level 5 years later. Children who had both higher fasting insulin and weight at 5 years of age showed much higher levels of systolic blood pressures, fasting plasma glucose, the homeostasis model assessment for insulin resistance (HOMA-IR) and triglycerides at 10 years of age. Conclusions Fasting plasma insulin at 5 years of age predicts weight gain and cardiovascular risk factors 5 year later in Chinese children of early childhood, but the absolute weight at 5 years of age did not predict subsequent change in fasting insulin. PMID:26047327

  8. Cerebral blood flow velocity increases during a single treatment with the molecular adsorbents recirculating system in patients with acute on chronic liver failure.

    PubMed

    Schmidt, L E; Svendsen, L B; Sørensen, V R; Hansen, B A; Larsen, F S

    2001-08-01

    The aim of this uncontrolled pilot study is to determine the effect of treatment with the molecular adsorbents recirculating system (MARS) on cerebral perfusion in patients with acute on chronic liver failure (AOCLF). In 8 patients (median age, 44 years; range, 35 to 52 years) admitted with AOCLF, a single 10-hour MARS treatment was performed. Hepatic encephalopathy (HE) was graded according to the Fogarty criteria. Changes in cerebral perfusion were determined by transcranial Doppler as mean flow velocity (V(mean)) in the middle cerebral artery. Arterial ammonia and bilirubin levels were monitored as a measure of the capability of the MARS to remove water-soluble and protein-bound toxins. During MARS treatment, HE grade improved in 3 patients and remained unchanged in 5 patients (P =.11). V(mean) increased from 42 cm/sec (range, 26 to 59 cm/sec) to 72 cm/sec (range, 52 to 106 cm/sec; P <.05), whereas arterial ammonia level decreased from 88 micromol/L (range, 45 to 117 micromol/L) to 71 micromol/L (range, 26 to 98 micromol/L; P <.05) and bilirubin level from 537 micromol/L (range, 324 to 877 micromol/L) to 351 micromol/L (range, 228 to 512 micromol/L; P <.05). In conclusion, cerebral perfusion is increased and levels of ammonia and bilirubin are reduced during MARS treatment in patients with AOCLF. PMID:11510016

  9. FXR and liver carcinogenesis

    PubMed Central

    Huang, Xiong-fei; Zhao, Wei-yu; Huang, Wen-dong

    2015-01-01

    Farnesoid X receptor (FXR) is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms: 1) FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2) FXR promotes liver regeneration and repair after injury; 3) FXR protects liver cells from death and enhances cell survival; 4) FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5) FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer. PMID:25500874

  10. Lead Poisoning in Childhood.

    ERIC Educational Resources Information Center

    Pueschel, Siegfried M., Ed.; Linakis, James G., Ed.; Anderson, Angela C., Ed.

    The magnitude of childhood lead poisoning has been inexplicably neglected by modern medicine and by legislators. However, since the 1970s, increased attention has been focused on lead poisoning, and advances have been made in several areas, including understanding of the neurodevelopmental and behavioral ramifications of lead poisoning, and…

  11. Increased levels of low-density lipoprotein cholesterol within the normal range as a risk factor for nonalcoholic fatty liver disease

    PubMed Central

    Zhu, Gui-Qi; Braddock, Martin; Zhang, Dong-Chu; Shi, Ke-Qing; Song, Dan; Zheng, Ming-Hua

    2016-01-01

    Objectives Dyslipidemia exists within the setting of NAFLD and the relationship of a normal level of low-density lipoprotein cholesterol (LDL-c) with NAFLD is largely unknown. This large population-based study aimed to investigate the association between LDL-c levels within the normal range and the incidence of NAFLD. Methods A total of 60527 subjects from 2 medical centers who had undergone liver ultrasonography were initially enrolled into this study. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver disease. Subjects were divided into 4 groups (Q1 to Q4) by normal LDL-c quartiles : Q1: ≤ 2.00, Q2: 2.10-2.35, Q3: 2.36-2.68 and Q4: 2.69-3.12 mmol/L. The odds ratios (OR), hazard ratio (HR) and 95% confidence intervals (CIs) for NAFLD were calculated across each quartile of LDL-c, using the Q1 as reference. Results The prevalence rates of NAFLD in a cross-sectional population from Q1 to Q4 were 19.34%, 25.86%, 35.65% and 42.08%, respectively. The OR for NAFLD in the cross-sectional population were 1.31 (95% CI 1.14-1.54), 1.73 (95% CI 1.46-2.04), and 1.82 (95% CI 1.49-2.23), respectively, after adjusting for known confounding variables. The HR for NAFLD in the longitudinal population were 1.23 (95% CI 1.12-1.35), 1.57 (95% CI 1.44-1.72) and 2.02 (95% CI 1.86-2.21), compared with Q1. Subjects with higher LDL-c level within the normal range had an increased cumulative incidence rate of NAFLD. Conclusions Increased levels of LDL-c within the normal range may play a significant role in the prevalence and incidence of NAFLD, independent of other confounding factors. PMID:26735337

  12. Decreased Cholesterol Uptake and Increased Liver X Receptor-Mediated Cholesterol Efflux Pathways During Prostaglandin F2 Alpha-Induced and Spontaneous Luteolysis in Sheep1

    PubMed Central

    Seto, Nickie L.; Bogan, Randy L.

    2015-01-01

    In nonprimate species, it has been well established that prostaglandin F2 alpha (PGF2alpha) initiates luteolysis. Changes in intracellular cholesterol concentrations caused by modulation of cholesterol uptake and efflux may mediate PGF2alpha-induced luteolysis. These changes in cholesterol efflux and uptake are controlled, in part, by the liver x receptors (LXR) alpha (NR1H3) and beta (NR1H2), nuclear receptors that increase expression of genes necessary for cholesterol efflux or limiting cholesterol uptake. Therefore, we hypothesized that PGF2alpha reduces expression of cholesterol uptake and increases expression of cholesterol efflux genes, mediated in part by enhanced LXR activity. To test this hypothesis, an induced luteolysis model was used whereby ewes were treated during their midluteal phase with saline or PGF2alpha and corpora lutea (CL) collected 12, 24, or 48 h later for determination of mRNA and protein concentrations by quantitative real-time PCR and Western blot analysis, respectively. As a complementary approach, CL undergoing spontaneous luteolysis were compared to midluteal phase CL. The lipoprotein receptors responsible for cholesterol uptake were significantly decreased in both luteolysis models. Expression of the LXR target gene ATP binding cassette subfamily A1 (ABCA1), an important mediator of cholesterol efflux, was significantly increased in both experimental models. Chromatin immunoprecipitation confirmed that PGF2alpha treatment resulted in enhanced NR1H3 and NR1H2 binding to the ABCA1 promoter. Qualitative changes in lipid droplet distribution were also observed following PGF2alpha treatment. These data support the hypothesis that reduced cholesterol uptake and increased efflux mediate luteolysis in sheep, which is partially controlled by PGF2alpha stimulation of LXR activity. PMID:25882703

  13. Liver-specific GH receptor gene-disrupted (LiGHRKO) mice have decreased endocrine IGF-I, increased local IGF-I, and altered body size, body composition, and adipokine profiles.

    PubMed

    List, Edward O; Berryman, Darlene E; Funk, Kevin; Jara, Adam; Kelder, Bruce; Wang, Feiya; Stout, Michael B; Zhi, Xu; Sun, Liou; White, Thomas A; LeBrasseur, Nathan K; Pirtskhalava, Tamara; Tchkonia, Tamara; Jensen, Elizabeth A; Zhang, Wenjuan; Masternak, Michal M; Kirkland, James L; Miller, Richard A; Bartke, Andrzej; Kopchick, John J

    2014-05-01

    GH is an important regulator of body growth and composition as well as numerous other metabolic processes. In particular, liver plays a key role in the GH/IGF-I axis, because the majority of circulating "endocrine" IGF-I results from GH-stimulated liver IGF-I production. To develop a better understanding of the role of liver in the overall function of GH, we generated a strain of mice with liver-specific GH receptor (GHR) gene knockout (LiGHRKO mice). LiGHRKO mice had a 90% decrease in circulating IGF-I levels, a 300% increase in circulating GH, and significant changes in IGF binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, IGFBP-5, and IGFBP-7. LiGHRKO mice were smaller than controls, with body length and body weight being significantly decreased in both sexes. Analysis of body composition over time revealed a pattern similar to those found in GH transgenic mice; that is, LiGHRKO mice had a higher percentage of body fat at early ages followed by lower percentage of body fat in adulthood. Local IGF-I mRNA levels were significantly increased in skeletal muscle and select adipose tissue depots. Grip strength was increased in LiGHRKO mice. Finally, circulating levels of leptin, resistin, and adiponectin were increased in LiGHRKO mice. In conclusion, LiGHRKO mice are smaller despite increased local mRNA expression of IGF-I in several tissues, suggesting that liver-derived IGF-I is indeed important for normal body growth. Furthermore, our data suggest that novel GH-dependent cross talk between liver and adipose is important for regulation of adipokines in vivo. PMID:24517230

  14. High-dose green tea polyphenol intake decreases CYP3A expression in a liver-specific manner with increases in blood substrate drug concentrations.

    PubMed

    Ikarashi, Nobutomo; Ogawa, Sosuke; Hirobe, Ryuta; Kusunoki, Yoshiki; Kon, Risako; Ochiai, Wataru; Sugiyama, Kiyoshi

    2016-06-30

    In recent years, the intake of functional foods containing high-doses of green tea polyphenols (GP) has been increasing. In this study, the long-term safety of high-dose GP was assessed from a pharmacokinetic point of view by focusing on the drug-metabolizing enzyme, cytochrome P450 (CYP). Mice were fed a diet containing 3% GP for 4weeks, and the CYP expression levels and activity were determined. The GP-treated group showed a significant decrease in the hepatic CYP3A and an increase in the hepatic CYP2C expression compared with the control group. CYP1A, CYP2D, and CYP2E expression were not different between the GP-treated and the control groups. In the small intestine, there were no differences in the CYP3A protein levels between the groups. The increase in the plasma triazolam concentration in the GP-treated group was observed. Although no changes were found in the hepatic CYP3A levels in mice receiving a diet containing 0.1% GP for 4weeks, a significant decrease was seen in the hepatic CYP3A level in mice receiving a diet containing 3% GP for only 1week. This study revealed that the intake of a high-dose GP results in a liver-specific decrease in the CYP3A expression level. The results also indicated that the effects of GP on CYP3A were not observed following the intake of a low-dose GP. In the future, caution should be taken in cases when functional foods containing a high-dose GP are concomitantly consumed with a CYP3A substrate drug. PMID:27130545

  15. Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats.

    PubMed

    Kim, Y W; Kim, J Y; Lee, S K

    1999-10-01

    In order to evaluate the role of visceral and subcutaneous fat tissue in insulin sensitivity and lipid metabolism, we measured the fasting levels of plasma free fatty acid (FFA) and insulin, glucose disappearance rate (Rd), and hepatic glucose production rate (HGP) after surgical removal of visceral (VF) or subcutaneous (SF) fat tissue in monosodium glutamate-obese (MSG-Ob) rats. Monosodium glutamate obesity was induced in rats by neonatal injection of MSG. Surgery to remove fat was done at 15 weeks of age. The experiments were done four weeks after the surgery. MSG-Ob rats showed increased levels of FFA, insulin, and HGP and decreased Rd compared to normal rats. In the VF group, the FFA level and HGP were decreased to normal values, Rd was partially normalized, but the level of insulin did not change significantly compared to MSG-Ob. In the SF group, FFA and Rd were partially normalized, but HGP was not suppressed significantly compared to MSG-Ob. These results suggest that visceral fat affects the insulin sensitivity of liver and FFA concentration more than subcutaneous fat; however, no significant difference was shown on whole body insulin sensitivity and fasting insulin concentration. PMID:10576150

  16. Liver transplantation with deceased ABO-incompatible donors is life-saving but associated with increased risk of rejection and post-transplant complications.

    PubMed

    Thorsen, Trygve; Dahlgren, Ulrika S; Aandahl, Einar Martin; Grzyb, Krzysztof; Karlsen, Tom H; Boberg, Kirsten M; Rydberg, Lennart; Naper, Christian; Foss, Aksel; Bennet, William

    2015-07-01

    ABO-incompatible (ABOi) liver transplantation (LT) with deceased donor organs is performed occasionally when no ABO-compatible (ABOc) graft is available. From 1996 to 2011, 61 ABOi LTs were performed in Oslo and Gothenburg. Median patient age was 51 years (range 13-75); 33 patients were transplanted on urgent indications, 13 had malignancy-related indications, and eight received ABOi grafts for urgent retransplantations. Median donor age was 55 years (range 10-86). Forty-four patients received standard triple immunosuppression with steroids, tacrolimus, and mycophenolate mofetil, and forty-four patients received induction with IL-2 antagonist or anti-CD20 antibody. Median follow-up time was 29 months (range 0-200). The 1-, 3-, 5-, and 10-year Kaplan-Meier estimates of patient survival (PS) and graft survival (GS) were 85/71%, 79/57%, 75/55%, and 59/51%, respectively, compared to 90/87%, 84/79%, 79/73%, and 65/60% for all other LT recipients in the same period. The 1-, 3-, 5-, and 10-year GS for A2 grafts were 81%, 67%, 62%, and 57%, respectively. In conclusion, ABOi LT performed with non-A2 grafts is associated with inferior graft survival and increased risk of rejection, vascular and biliary complications. ABOi LT with A2 grafts is associated with acceptable graft survival and can be used safely in urgent cases. PMID:25736519

  17. Higher Estimated Net Endogenous Acid Production May Be Associated with Increased Prevalence of Nonalcoholic Fatty Liver Disease in Chinese Adults in Hong Kong

    PubMed Central

    Chan, Ruth; Wong, Vincent Wai-Sun; Chu, Winnie Chiu-Wing; Wong, Grace Lai-Hung; Li, Liz Sin; Leung, Jason; Chim, Angel Mei-Ling; Yeung, David Ka-Wai; Sea, Mandy Man-Mei; Woo, Jean; Chan, Francis Ka-Leung; Chan, Henry Lik-Yuen

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto’s method and potential renal acid load (PRAL) was calculated using Remer’s method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to

  18. Propiconazole increases reactive oxygen species levels in mouse hepatic cells in culture and in mouse liver by a cytochrome P450 enzyme mediated process

    EPA Science Inventory

    Propiconazole induces hepatocarcinomas and hepatoadenomas in mice and is a rat liver tumor promoter. Transcriptional, proteomic, metabolomic and biochemical studies of hepatic tissues from mice treated with propiconazole under the conditions of the chronic bioassay indicate that ...

  19. [Tumours and liver transplants].

    PubMed

    Mejzlík, Vladimír; Husová, Libuše; Kuman, Milan; Štěpánková, Soňa; Ondrášek, Jiří; Němec, Petr

    2015-01-01

    Liver transplantation as a curative treatment method can be used for selected primary liver tumours, in particular for hepatocellular carcinoma and rather rare semi-malignant tumours such as epithelioid hemangioendothelioma, further for infiltration of liver by metastatic neuroendocrine tumours (provided that metastases are only located in the liver and the primary tumour was removed) and for benign tumours (hemangiomas and adenomas) with oppression symptoms and size progression. Cholangiocarcinoma is not indicated for liver transplantation at the CKTCH Brno. In recent years liver transplants for hepatocellular carcinoma have increased and hepatocellular carcinoma has also been more frequently found ex post, in the explanted livers. Liver transplantation is indicated in selected patients with a good chance of long-term survival after liver transplantation (a generally accepted limit is 5 year survival of 50 % after transplantation). By 20 March 2015 there were liver transplants carried out on 38 patients - in 25 of them was hepatocellular carcinoma diagnosed before transplantation and in 13 it was found in the liver explants. 5 year survival following transplantation is reached by 53 % of this cohort. 32 % patients suffered from chronic hepatitis C. The longest surviving (32 years) patient at CKTCH Brno had liver transplanted for a big fibrolamellar hepatocellular carcinoma, which points to the prognostic significance of tumour histology: the criterion only considered in some indication schemes for practical reasons. Benign liver tumours (adenomatosis, cystadenoma, hemangioma with oppression symptoms) are rather rare indications and the transplantation results are favourable. 4 patients underwent transplantation for infiltration of liver by carcinoid, tumour recurrence occurred in one. PMID:26375706

  20. Development of Strategies to Increase Enrollment in Clinical Trials for Children With Cancer

    ClinicalTrials.gov

    2014-02-12

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Leukemia; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Psychosocial Effects of Cancer and Its Treatment; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  1. Childhood Obesity

    ERIC Educational Resources Information Center

    Yuca, Sevil Ari, Ed.

    2012-01-01

    This book aims to provide readers with a general as well as an advanced overview of the key trends in childhood obesity. Obesity is an illness that occurs due to a combination of genetic, environmental, psychosocial, metabolic and hormonal factors. The prevalence of obesity has shown a great rise both in adults and children in the last 30 years.…

  2. Second Childhood.

    ERIC Educational Resources Information Center

    Arluke, Arnold; Levin, Jack

    1982-01-01

    Ageism (unfair stereotyping of older adults), deeply embedded in the culture of 20th-century America, is reinforced by television and newspapers. The media depict old people as rigid, meddlesome, sexless, conservative, unhealthy, and forgetful. Most pernicious of all old age stereotypes is that of second childhood. Popular culture portrays…

  3. [Liver and drug metabolism].

    PubMed

    Mikheeva, O M

    2011-01-01

    Liver metabolism aims to change the biological activity of drugs to make them water-soluble to be excreted with bile and urine. The degree of metabolism depends on fermentative capacity for each drag (P450 fermentative system is localized in microsomal fraction of hepatocyte). Metabolism ability also changes under the influence of other substances. Liver diseases lead up to decrease of drug clirens and to increase the semi-excretion time because of reduction of liver metabolism. Therefore the drags usually undergoing intensive liver metabolism necessitate a high risk of overdose when liver diseases present. On the other hand no risk of overdose exist when drags with low liver metabolism are used. PMID:21560652

  4. Glucocorticosteroids trigger reactivation of human cytomegalovirus from latently infected myeloid cells and increase the risk for HCMV infection in D+R+ liver transplant patients

    PubMed Central

    Van Damme, Ellen; Sauviller, Sarah; Lau, Betty; Kesteleyn, Bart; Griffiths, Paul; Burroughs, Andrew; Emery, Vincent; Sinclair, John

    2015-01-01

    Graft rejection in transplant patients is managed clinically by suppressing T-cell function with immunosuppressive drugs such as prednisolone and methylprednisolone. In such immunocompromised hosts, human cytomegalovirus (HCMV) is an important opportunistic pathogen and can cause severe morbidity and mortality. Currently, the effect of glucocorticosteroids (GCSs) on the HCMV life cycle remains unclear. Previous reports showed enhanced lytic replication of HCMV in vitro in the presence of GCSs. In the present study, we explored the implications of steroid exposure on latency and reactivation. We observed a direct effect of several GCSs used in the clinic on the activation of a quiescent viral major immediate-early promoter in stably transfected THP-1 monocytic cells. This activation was prevented by the glucocorticoid receptor (GR) antagonist Ru486 and by shRNA-mediated knockdown of the GR. Consistent with this observation, prednisolone treatment of latently infected primary monocytes resulted in HCMV reactivation. Analysis of the phenotype of these cells showed that treatment with GCSs was correlated with differentiation to an anti-inflammatory macrophage-like cell type. On the basis that these observations may be pertinent to HCMV reactivation in post-transplant settings, we retrospectively evaluated the incidence, viral kinetics and viral load of HCMV in liver transplant patients in the presence or absence of GCS treatment. We observed that combination therapy of baseline prednisolone and augmented methylprednisolone, upon organ rejection, significantly increased the incidence of HCMV infection in the intermediate risk group where donor and recipient are both HCMV seropositive (D+R+) to levels comparable with the high risk D+R− group. PMID:25312585

  5. Glucocorticosteroids trigger reactivation of human cytomegalovirus from latently infected myeloid cells and increase the risk for HCMV infection in D+R+ liver transplant patients.

    PubMed

    Van Damme, Ellen; Sauviller, Sarah; Lau, Betty; Kesteleyn, Bart; Griffiths, Paul; Burroughs, Andrew; Emery, Vincent; Sinclair, John; Van Loock, Marnix

    2015-01-01

    Graft rejection in transplant patients is managed clinically by suppressing T-cell function with immunosuppressive drugs such as prednisolone and methylprednisolone. In such immunocompromised hosts, human cytomegalovirus (HCMV) is an important opportunistic pathogen and can cause severe morbidity and mortality. Currently, the effect of glucocorticosteroids (GCSs) on the HCMV life cycle remains unclear. Previous reports showed enhanced lytic replication of HCMV in vitro in the presence of GCSs. In the present study, we explored the implications of steroid exposure on latency and reactivation. We observed a direct effect of several GCSs used in the clinic on the activation of a quiescent viral major immediate-early promoter in stably transfected THP-1 monocytic cells. This activation was prevented by the glucocorticoid receptor (GR) antagonist Ru486 and by shRNA-mediated knockdown of the GR. Consistent with this observation, prednisolone treatment of latently infected primary monocytes resulted in HCMV reactivation. Analysis of the phenotype of these cells showed that treatment with GCSs was correlated with differentiation to an anti-inflammatory macrophage-like cell type. On the basis that these observations may be pertinent to HCMV reactivation in post-transplant settings, we retrospectively evaluated the incidence, viral kinetics and viral load of HCMV in liver transplant patients in the presence or absence of GCS treatment. We observed that combination therapy of baseline prednisolone and augmented methylprednisolone, upon organ rejection, significantly increased the incidence of HCMV infection in the intermediate risk group where donor and recipient are both HCMV seropositive (D+R+) to levels comparable with the high risk D+R- group. PMID:25312585

  6. Survivors of childhood cancer.

    PubMed

    Bradwell, Moira

    2009-05-01

    Treatment of childhood cancer aims to cure with minimum risk to the patient's subsequent health. Monitoring the long-term effects of treatment on children and young adults is now an essential part of the continued care of survivors. Late effects include: impact on growth, development and intellectual function; organ system impairment; the development of second malignancies; and psychosocial problems. These can adversely affect long-term survival and the quality of life. In the UK, models of long-term follow up for survivors of childhood cancer vary from centre to centre but nurses have a significant role to play. Combining the nurse specialist role with that of the advanced practitioner ensures that the goals of improving the quality of nursing care to the survivors of childhood cancer are achieved and maximises the nursing contribution to their follow up. With the number of childhood cancer survivors increasing, providing holistic, health promotional care, tailored to the specific needs of survivors will be crucial for their future. PMID:19505060

  7. [Childhood hypertension].

    PubMed

    Takemura, Tsukasa

    2015-11-01

    For accurate diagnosis of childhood hypertension, selection of appropriate manchette size according to the child age and the circumstantial size of upper limb is essentially important. In addition, except for the emergency case of hypertension, repeated measurement of blood pressure would be desirable in several weeks interval. Recently, childhood hypertension might be closely related to the abnormality of maternal gestational period caused by the strict diet and the maternal smoking. Developmental Origins of Health and Disease(DOHaD) theory is now highlighted in the pathogenesis of adulthood hypertension. To prevent hypertension of small-for-date baby in later phase of life, maternal education for child nursing should be conducted. In children, secondary hypertension caused by renal, endocrinologic, or malignant disease is predominant rather than idiopathic hypertension. PMID:26619664

  8. Kidney Injury in Liver Disease.

    PubMed

    Regner, Kevin R; Singbartl, Kai

    2016-07-01

    Acute kidney injury (AKI) occurs frequently in patients with liver disease and increases morbidity and mortality. Hepatorenal syndrome is a common cause of AKI in patients with decompensated cirrhosis and is due to alterations in systemic and renal hemodynamics. Serum creatinine-based estimation of kidney function is a key component of the Model for End-stage Liver Disease score in liver transplant candidates. Continuous renal replacement therapy is used in critically ill patients with liver failure and AKI. Simultaneous liver-kidney transplantation (SLK) may be required in patients with liver failure and prolonged AKI. Identification of appropriate candidates for SLK remains controversial. PMID:27339675

  9. Fatty liver accompanies an increase in Lactobacillus species in the hind gut of C57BL/6 mice fed a high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High-fat diets can produce obesity and have been linked to the development of nonalcoholic fatty liver disease (NAFLD). They have also been shown to induce changes in the gut microbiome, metabolic products of which have also been linked to NAFLD. This study tested the hypothesis that high-fat fee...

  10. Increased 4-hydroxynonenal protein adducts in male GSTA4–4/PPAR-alpha double knockout mice enhance injury during early stages of alcoholic liver disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To test the significance of lipid peroxidation in the development of alcoholic liver injury, an ethanol (EtOH) liquid diet was fed to male wild type 129/SvJ mice, and glutathione S-transferase A4-4 null (GSTA4-/-) mice for 40 d. GSTA4-/- mice were also crossed with peroxisome proliferator-activated ...

  11. Increased accumulation of 4-hydroxynonenal adducts in male GSTA4/PPAR alpha double knockout mice enhances injury during early stages of alcoholic liver disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hepatic lipid peroxidation and accumulation of aldehyde-adducted proteins occur early in alcohol-mediated injury and are postulated to mediate the subsequent pro-inflammatory and fibrotic responses observed in alcoholic liver disease. To test the significance of lipid peroxidation formation in the ...

  12. Liver transplant

    MedlinePlus

    ... series References Keefe EB. Hepatic failure and liver transplantation. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... 2011:chap 157. Martin P, Rosen HR. Liver transplantation. In: Feldman M, Friedman LS, Brandt LJ, eds. ...

  13. Liver spots

    MedlinePlus

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun ...

  14. Liver biopsy

    MedlinePlus

    ... Test is Performed The biopsy helps diagnose many liver diseases . The procedure also helps assess the stage (early, advanced) of liver disease. This is especially important in hepatitis C infection. ...

  15. Liver Diseases

    MedlinePlus

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

  16. Mesenchymal Hamartoma of the Liver in an Infant With Beckwith-Wiedemann Syndrome: A Rare Condition Mimicking Hepatoblastoma.

    PubMed

    Abrahao-Machado, Lucas F; de Macedo, Fabiane C; Dalence, Carlos; Stambo, Glenn; Abrahao-Machado, Eduarda F; Abrahao-Machado, Elaine C F; Bahrami, Armita; Nascimento, Antonio G

    2015-07-01

    Patients with Beckwith-Wiedemann syndrome (BWS) are known to be at an increased risk for childhood malignancies, particularly Wilms tumor and hepatoblastoma. We report a case of genetically confirmed BWS in a 5-month-old girl who presented with a 9.5-cm abdominal mass associated with elevated α-fetoprotein levels. The clinical impression was strongly suggestive of hepatoblastoma. Histologic examination of the surgically excised mass revealed mesenchymal hamartoma of the liver (MHL), a benign hepatic neoplasm. PMID:26203458

  17. Liver Biopsy

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​. Alternate Language URL Español Liver Biopsy Page Content On this page: What is ... Points to Remember Clinical Trials What is a liver biopsy? A liver biopsy is a procedure that ...

  18. Liver Biopsy

    MedlinePlus

    ... PDF, 341 KB)​​​​. Alternate Language URL Español Liver Biopsy Page Content On this page: What is a ... to Remember Clinical Trials What is a liver biopsy? A liver biopsy is a procedure that involves ...

  19. Liver transplantation☆

    PubMed Central

    Rossi, M.; Mennini, G.; Lai, Q.; Ginanni Corradini, S.; Drudi, F.M.; Pugliese, F.; Berloco, P.B.

    2007-01-01

    Orthotopic liver transplantation (OLT) involves the substitution of a diseased native liver with a normal liver (or part of one) taken from a deceased or living donor. Considered an experimental procedure through the 1980s, OLT is now regarded as the treatment of choice for a number of otherwise irreversible forms of acute and chronic liver disease. The first human liver transplantation was performed in the United States in 1963 by Prof. T.E. Starzl of the University of Colorado. The first OLT to be performed in Italy was done in 1982 by Prof. R. Cortesini. The procedure was successfully performed at the Policlinico Umberto I of the University of Rome (La Sapienza). The paper reports the indications for liver transplantation, donor selection and organ allocation in our experience, surgical technique, immunosuppression, complications and results of liver transplantation in our center. PMID:23396075

  20. Studies on immunoproteasome in human liver. Part I: Absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis

    SciTech Connect

    Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena; Mishto, Michele; Santoro, Aurelia; Fiorentino, Michelangelo; Capri, Miriam; Cescon, Matteo; Grazi, Gian Luca; Grigioni, Walter Franco; D'Errico-Grigioni, Antonia; Franceschi, Claudio

    2010-06-25

    Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical data have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.

  1. Fatty liver disease in children: eat now pay later

    PubMed Central

    Fitzpatrick, Emer; Dhawan, Anil

    2010-01-01

    Introduction With the recent epidemic in childhood obesity, nonalcoholic fatty liver disease (NAFLD) has become an emerging problem and a common cause of chronic liver disease in children. Methods In this review, the most recent insights on the pathogenesis, diagnosis, natural history, and treatment of NAFLD in children are discussed. PMID:20305757

  2. Non-Alcoholic Fatty Liver Disease in Children: Focus on Nutritional Interventions

    PubMed Central

    Yang, Min; Gong, Sitang; Ye, Shui Qing; Lyman, Beth; Geng, Lanlan; Chen, Peiyu; Li, Ding-You

    2014-01-01

    With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD) has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD. PMID:25353664

  3. Non-alcoholic fatty liver disease in children: focus on nutritional interventions.

    PubMed

    Yang, Min; Gong, Sitang; Ye, Shui Qing; Lyman, Beth; Geng, Lanlan; Chen, Peiyu; Li, Ding-You

    2014-11-01

    With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD) has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD. PMID:25353664

  4. Myths of Childhood.

    ERIC Educational Resources Information Center

    Paris, Joel

    This book calls into question the degree to which early childhood experiences affect psychological development, critiquing three related myths: (1) personality is formed by early childhood experiences; (2) mental disorders are caused by early childhood experiences; and (3) effective psychotherapy depends on reconstructing childhood experiences.…

  5. Overview of Childhood Schizophrenia.

    ERIC Educational Resources Information Center

    Bryan, Betsy

    Childhood schizophrenia is a rare but serious disorder with complex symptoms that affect children and their families. Childhood schizophrenia was once the term applied for all childhood psychoses, including autism and mood disorders, but more recently researchers have distinguished childhood schizophrenia from other disorders. There are differing…

  6. Increased Whole-Body and Sustained Liver Cortisol Regeneration by 11β-Hydroxysteroid Dehydrogenase Type 1 in Obese Men With Type 2 Diabetes Provides a Target for Enzyme Inhibition

    PubMed Central

    Stimson, Roland H.; Andrew, Ruth; McAvoy, Norma C.; Tripathi, Dhiraj; Hayes, Peter C.; Walker, Brian R.

    2011-01-01

    OBJECTIVE The cortisol-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies glucocorticoid levels in liver and adipose tissue. 11β-HSD1 inhibitors are being developed to treat type 2 diabetes. In obesity, 11β-HSD1 is increased in adipose tissue but decreased in liver. The benefits of pharmacological inhibition may be reduced if hepatic 11β-HSD1 is similarly decreased in obese patients with type 2 diabetes. To examine this, we quantified in vivo whole-body, splanchnic, and hepatic 11β-HSD1 activity in obese type 2 diabetic subjects. RESEARCH DESIGN AND METHODS Ten obese men with type 2 diabetes and seven normal-weight control subjects were infused with 9,11,12,12-[2H]4cortisol (40%) and cortisol (60%) at 1.74 mg/h. Adrenal cortisol secretion was suppressed with dexamethasone. Samples were obtained from the hepatic vein and an arterialized hand vein at steady state and after oral administration of cortisone (5 mg) to estimate whole-body and liver 11β-HSD1 activity using tracer dilution. RESULTS In obese type 2 diabetic subjects, the appearance rate of 9,12,12-[2H]3cortisol in arterialized blood was increased (35 ± 2 vs. 29 ± 1 nmol/min, P < 0.05), splanchnic 9,12,12-[2H]3cortisol production was not reduced (29 ± 6 vs. 29 ± 6 nmol/min), and cortisol appearance in the hepatic vein after oral cortisone was unchanged. CONCLUSIONS Whole-body 11β-HSD1 activity is increased in obese men with type 2 diabetes, whereas liver 11β-HSD1 activity is sustained, unlike in euglycemic obesity. This supports the concept that inhibitors of 11β-HSD1 are likely to be most effective in obese type 2 diabetic subjects. PMID:21266326

  7. Dual control mechanism for heme oxygenase: tin(IV)-protoporphyrin potently inhibits enzyme activity while markedly increasing content of enzyme protein in liver.

    PubMed Central

    Sardana, M K; Kappas, A

    1987-01-01

    Tin(IV)-protoporphyrin (Sn-protoporphyrin) potently inhibits heme degradation to bile pigments in vitro and in vivo, a property that confers upon this synthetic compound the ability to suppress a variety of experimentally induced and naturally occurring forms of jaundice in animals and humans. Utilizing rat liver heme oxygenase purified to homogeneity together with appropriate immunoquantitation techniques, we have demonstrated that Sn-protoporphyrin possesses the additional property of potently inducing the synthesis of heme oxygenase protein in liver cells while, concurrently, completely inhibiting the activity of the newly formed enzyme. Substitution of tin for the central iron atom of heme thus leads to the formation of a synthetic heme analogue that regulates heme oxygenase by a dual mechanism, which involves competitive inhibition of the enzyme for the natural substrate heme and simultaneous enhancement of new enzyme synthesis. Cobaltic(III)-protoporphyrin (Co-protoporphyrin) also inhibits heme oxygenase activity in vitro, but unlike Sn-protoporphyrin it greatly enhances the activity of the enzyme in the whole animal. Co-protoporphyrin also acts as an in vivo inhibitor of heme oxygenase; however, its inducing effect on heme oxygenase synthesis is so pronounced as to prevail in vivo over its inhibitory effect on the enzyme. These studies show that certain synthetic heme analogues possess the ability to simultaneously inhibit as well as induce the enzyme heme oxygenase in liver. The net balance between these two actions, as reflected in the rate of heme oxidation activity in the whole animal, appears to be influenced by the nature of the central metal atom of the synthetic metalloporphyrin. Images PMID:3470805

  8. The frequency of multipotent CD133(+)CD45RA(-)CD34(+) hematopoietic stem cells is not increased in fetal liver compared with adult stem cell sources.

    PubMed

    Radtke, Stefan; Haworth, Kevin G; Kiem, Hans-Peter

    2016-06-01

    The cell surface marker CD133 has been used to describe a revised model of adult human hematopoiesis, with hematopoietic stem cells and multipotent progenitors (HSCs/MPPs: CD133(+)CD45RA(-)CD34(+)) giving rise to lymphomyeloid-primed progenitors (LMPPs: CD133(+)CD45RA(+)CD34(+)) and erythromyeloid progenitors (EMPs: CD133(low)CD45RA(-)CD34(+)). Because adult and fetal hematopoietic stem and progenitor cells (HSPCs) differ in their gene expression profile, differentiation capabilities, and cell surface marker expression, we were interested in whether the reported segregation of lineage potentials in adult human hematopoiesis would also apply to human fetal liver. CD133 expression was easily detected in human fetal liver cells, and the defined hematopoietic subpopulations were similar to those found for adult HSPCs. Fetal HSPCs were enriched for EMPs and HSCs/MPPs, which were primed toward erythromyeloid differentiation. However, the frequency of multipotent CD133(+)CD45RA(-)CD34(+) HSPCs was much lower than previously reported and comparable to that of umbilical cord blood. We noted that engraftment in NSG (NOD scid gamma [NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ]) mice was driven mostly by LMPPs, confirming recent findings that repopulation in mice is not a unique feature of multipotent HSCs/MPPs. Thus, our data challenge the general assumption that human fetal liver contains a greater percentage of multipotent HSCs/MPPs than any adult HSC source, and the mouse model may have to be re-evaluated with respect to the type of readout it provides. PMID:27016273

  9. Online Early Childhood Professional Development: Selected Experiences

    ERIC Educational Resources Information Center

    Olsen, Heather

    2010-01-01

    Early childhood professional development opportunities are expanding rapidly throughout the country. With nearly 12 million children under the age of 5 in some kind of early childhood setting, there is an effort to increase the quality of care and education. In fact, 97% of states require child care professionals to commit to ongoing professional…

  10. Attachment in Middle Childhood: Progress and Prospects

    ERIC Educational Resources Information Center

    Bosmans, Guy; Kerns, Kathryn A.

    2015-01-01

    Contrary to the substantial amount of research on infant, preschool, adolescent, and adult attachment, middle childhood has long been neglected by the international attachment research community. In the past two decades, however, there has been a steep increase in research focusing on middle childhood attachment. This article provides an overview…

  11. Treatment of Childhood Obesity: A Systematic Review

    ERIC Educational Resources Information Center

    Staniford, Leanne J.; Breckon, Jeff D.; Copeland, Robert J.

    2012-01-01

    Childhood obesity trends have increased dramatically over the past three decade's. The purpose of this quantitative systematic review is to provide an update of the evidence, illustrating the efficacy of childhood obesity treatment, considering whether treatment fidelity has been measured and/or reported and whether this related to the treatment…

  12. Interactive media for childhood obesity prevention

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Childhood obesity is a worldwide pandemic that increases the risk of type 2 diabetes, cardiovascular diseases, and multiple cancers, and reduces quality of life and functional ability. Fruit, 100% juice, and vegetable (FJV) intake, and physical activity (PA) are behaviors related to childhood obesit...

  13. Endocrinopathies in Survivors of Childhood Neoplasia

    PubMed Central

    Barnes, Nicole; Chemaitilly, Wassim

    2014-01-01

    Advancements in cancer treatments have increased the number of survivors of childhood cancers. Endocrinopathies are common complications following cancer therapy and may occur decades later. The objective of the current review is to address the main endocrine abnormalities detected in childhood cancer survivors including disorders of the hypothalamic-pituitary axis, thyroid, puberty, gonads, bone, body composition, and glucose metabolism. PMID:25295241

  14. Striving for Quality in Early Childhood Inclusion

    ERIC Educational Resources Information Center

    Brancato, Kimberly

    2013-01-01

    An essential component of best practice in the field of early childhood special education is the inclusion of children with disabilities in typical early childhood settings. As the practice of inclusion has increased in recent years it has become imperative to ensure that children with disabilities attend quality programs. The main purpose of this…

  15. An increased diversity of HCV isolates were characterized among 393 patients with liver disease in China representing six genotypes, 12 subtypes, and two novel genotype 6 variants

    PubMed Central

    Gu, Lin; Tong, Wangxia; Yuan, Manqiong; Lu, Teng; Li, Chunhua; Lu, Ling

    2013-01-01

    Background We have recently determined HCV isolates among volunteer blood donors and IDUs in southern China and revealed the genotype distribution patterns not only different between the two studied cohorts but also from what we have sampled in 2002. A changed pattern could have also occurred among patients with liver disease. Materials/Methods Both E1 and NS5B sequences of HCV were characterized among 393 patients with liver disease followed by phylogenetic analysis. Results Six HCV genotypes, 12 subtypes (1b: 65.9%, 6a: 17.1%, 2a: 7.4%, 3a: 3.6%, 3b: in 3.3%, 6e: 0.76%, and 1a, 1c, 2b, 2f, 4d, and 5a each 0.25%), and two novel genotype 6 variants were classified, showing the greatest complexity of HCV hitherto found in China. Although the predominance of 1b followed by 6a is largely consistent with what we have sampled in 2002, the identification of single isolates of 1c, 2f, 4d, 5a, and two novel HCV-6 variants were first reported. Excluding 4d from a European visitor, all the others were from Chinese patients. Since the 6a proportion (17.1%, 67/393) was unexpectedly lower than what we have recently detected among blood donors (34.8%, 82/236) and IDUs (51.5%, 70/136), further statistical analyses were conducted. Comparison of the mean ages showed that among the 393 patients, those infected with 1b were significantly (6.7 years) older than those with 6a, while the 393 patients as a whole were significantly older than the 236 blood donors (8.4 years) and 136 IDUs (12.6 years) we have recently reported. Explanations are that younger individuals had higher proportions of 6a infections while patients with liver disease could have acquired their infections earlier than volunteer blood donors and IDUs. Conclusion Among 393 patients with liver disease, a great diversity in HCV was detected, which reflects a constantly changing pattern of HCV genotypes in China over time. PMID:23706765

  16. Early Childhood Education in Scandinavia.

    ERIC Educational Resources Information Center

    Austin, Gilbert R.; Dittman, Laura

    This article discusses the move toward greater equality of educational opportunity in Scandinavia with particular emphasis on early childhood education. The increasing demand for preschool education in Denmark, Finland, Norway and Sweden is related to low birth rates together with increased employment of women and the general demand for equality…

  17. Annotation: Childhood-Onset Schizophrenia--Clinical and Treatment Issues

    ERIC Educational Resources Information Center

    Asarnow, Joan Rosenbaum; Tompson, Martha C.; McGrath, Emily P.

    2004-01-01

    Background: In the past 10 years, there has been increased research on childhood-onset schizophrenia and clear advances have been achieved. Method: This annotation reviews the recent clinical and treatment literature on childhood-onset schizophrenia. Results: There is now strong evidence that the syndrome of childhood-onset schizophrenia exists…

  18. N-3 Polyunsaturated Fatty Acids Improve Liver Lipid Oxidation-Related Enzyme Levels and Increased the Peroxisome Proliferator-Activated Receptor α Expression Level in Mice Subjected to Hemorrhagic Shock/Resuscitation

    PubMed Central

    Zhang, Li; Tian, Feng; Gao, Xuejin; Wang, Xinying; Wu, Chao; Li, Ning; Li, Jieshou

    2016-01-01

    Appropriate metabolic interventions after hemorrhagic shock/resuscitation injury have not yet been identified. We aimed to examine the effects of fish oil on lipid metabolic intervention after hemorrhagic shock/resuscitation. Firstly, 48 C57BL/6 mice were assigned to six groups (n = 8 per group). The sham group did not undergo surgery, while mice in the remaining groups were sacrificed 1–5 days after hemorrhagic shock/resuscitation. In the second part, mice were treated with saline or fish oil (n = 8 per group) five days after injury. We determined serum triglyceride levels and liver tissues were collected and prepared for qRT-PCR or Western blot analysis. We found that triglyceride levels were increased five days after hemorrhagic shock/resuscitation, but decreased after addition of fish oil. After injury, the protein and gene expression of carnitine palmitoyltransferase 1A, fatty acid transport protein 1, and peroxisome proliferator-activated receptor-α decreased significantly in liver tissue. In contrast, after treatment with fish oil, the expression levels of these targets increased compared with those in the saline group. The present results suggest n-3 polyunsaturated fatty acids could improve lipid oxidation-related enzymes in liver subjected to hemorrhagic shock/resuscitation. This function is possibly accomplished through activating the peroxisome proliferator-activated receptor-α pathway. PMID:27110821

  19. N-3 Polyunsaturated Fatty Acids Improve Liver Lipid Oxidation-Related Enzyme Levels and Increased the Peroxisome Proliferator-Activated Receptor α Expression Level in Mice Subjected to Hemorrhagic Shock/Resuscitation.

    PubMed

    Zhang, Li; Tian, Feng; Gao, Xuejin; Wang, Xinying; Wu, Chao; Li, Ning; Li, Jieshou

    2016-01-01

    Appropriate metabolic interventions after hemorrhagic shock/resuscitation injury have not yet been identified. We aimed to examine the effects of fish oil on lipid metabolic intervention after hemorrhagic shock/resuscitation. Firstly, 48 C57BL/6 mice were assigned to six groups (n = 8 per group). The sham group did not undergo surgery, while mice in the remaining groups were sacrificed 1-5 days after hemorrhagic shock/resuscitation. In the second part, mice were treated with saline or fish oil (n = 8 per group) five days after injury. We determined serum triglyceride levels and liver tissues were collected and prepared for qRT-PCR or Western blot analysis. We found that triglyceride levels were increased five days after hemorrhagic shock/resuscitation, but decreased after addition of fish oil. After injury, the protein and gene expression of carnitine palmitoyltransferase 1A, fatty acid transport protein 1, and peroxisome proliferator-activated receptor-α decreased significantly in liver tissue. In contrast, after treatment with fish oil, the expression levels of these targets increased compared with those in the saline group. The present results suggest n-3 polyunsaturated fatty acids could improve lipid oxidation-related enzymes in liver subjected to hemorrhagic shock/resuscitation. This function is possibly accomplished through activating the peroxisome proliferator-activated receptor-α pathway. PMID:27110821

  20. Sulfasalazine prevents the increase in TGF-β, COX-2, nuclear NFκB translocation and fibrosis in CCl4-induced liver cirrhosis in the rat.

    PubMed

    Chávez, E; Castro-Sánchez, L; Shibayama, M; Tsutsumi, V; Moreno, M G; Muriel, P

    2012-09-01

    It has been demonstrated that this sulfasalazine (SF) inhibits the nuclear factor κB (NFκB) pathway, which regulates important genes during inflammation and immune answer. The aim of this work was to evaluate the effects of SF on carbon tetrachloride (CCl(4))-induced liver fibrosis. We formed the following experimental groups of rats: controls, damage induced by chronic CCl(4) (0.4 g/kg, intraperitoneally, three times a week for 8 weeks) administration and CCl(4) + SF (100 mg/kg/day, postoperatively for 8 weeks) administration. We determined the activities of alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), cyclooxygenase (COX)-1 and COX-2, lipid peroxidation, glutathione levels, collagen content, expression of transforming growth factor-β (TGF-β) and nuclear translocation of NFκB. SF was capable to inhibit the ALT and γ-GTP elevated levels induced with the CCl(4) administration. SF had antioxidant properties, prevented the lipid peroxidation and the imbalance of reduced and oxidized glutathione produced by CCl(4). Importantly, SF blocked the accumulation of collagen in the liver, the expression of TGF-β, the nuclear translocation of NFκB and the activity of COX-2, all induced with the administration of CCl(4) in the rat. These results show that SF has strong antifibrotic properties because of its antioxidant properties and its ability to prevent nuclear translocation of NFκB and consequently the expression of TGF-β and the activity of COX-2. PMID:22381741

  1. "Learning Stories"--Crossing Borders: Introducing Qualitative Early Childhood Observation Techniques to Early Childhood Practitioners in Saudi Arabia

    ERIC Educational Resources Information Center

    Nyland, Berenice; Alfayez, Shatha

    2012-01-01

    Early childhood education has become a focus of government policy across the world. Part of the present increased interest in early childhood education has been a focus on curriculum frameworks and socio/cultural methods of assessment. Currently, New Zealand has emerged as a world leader in early childhood education, and observation and assessment…

  2. Pregnancy after liver transplantation.

    PubMed

    Ramirez, Carlo B; Doria, Cataldo

    2014-11-01

    Women constitute >30% of patients undergoing liver transplantation (orthotopic liver transplantation, OLT) and about 8% are of reproductive age, and 5% are pediatric females who will mostly survive into adulthood and will consider pregnancy. Although pregnancy in OLT recipients is associated with an increased incidence of hypertension, preeclampsia, anemia, preterm deliveries, and cesarean section, acute rejection and liver allograft loss do not appear to be increased and pregnancy-related maternal death is uncommon. The incidence of structural malformations in the newborn of liver transplant recipients is reported to be 4.4%, which is similar to the rate of 3-5% in the US general population. Patients are advised to defer conception for at least 1-2 years after OLT, while maintaining effective contraception. Pregnancy after OLT usually results in a favorable maternal and neonatal outcome when there is coordinated pre- and perinatal care by a multidisciplinary team composed of obstetric-gynecologists, and a transplant team. PMID:25257968

  3. Teen Obesity May Mean Liver Disease Later

    MedlinePlus

    ... news/fullstory_159416.html Teen Obesity May Mean Liver Disease Later Study found risk increased as weight went ... obese could be at increased risk for severe liver disease later in life, a new study suggests. The ...

  4. A Narrative Inquiry of Technology as a Viable Support to Revitalizing and Increasing the Choctaw Language among American Indians and Non-Indians in an Early Childhood Setting

    ERIC Educational Resources Information Center

    McClour, Christine Elizabeth

    2015-01-01

    In the past several decades the global village has witnessed a rapid decline in the number of indigenous languages. This study was a narrative inquiry within a qualitative methodology. Two research questions were used to analyze the narratives of Choctaw Nation Head Start teachers concerning technology usage for increasing, and revitalizing the…

  5. Including Young Children With "New" Chronic Illnesses in an Early Childhood Education Setting.

    ERIC Educational Resources Information Center

    Fauvre, Mary

    1988-01-01

    Presents suggestions for successfully including young children with "new" life-threatening, chronic illnesses -- various types of cancer, heart, liver, and kidney diseases -- in early childhood education classes. (BB)

  6. Alcoholic liver disease: The gut microbiome and liver crosstalk

    PubMed Central

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier or preventing cellular responses to microbial products protect from experimental alcoholic liver disease. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of alcoholic liver disease. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship and consequences for alcoholic liver disease. We also discuss how the liver affects the intestinal microbiota. PMID:25872593

  7. Analgesia after liver transplantation

    PubMed Central

    Milan, Zoka

    2015-01-01

    This article addresses postoperative analgesia in patients with end-stage liver disease who have undergone liver transplantation (LT). Postoperative analgesia determines how patients perceive LT. Although important, this topic is underrepresented in the current literature. With an increased frequency of fast tracking in LT, efficient intra- and postoperative analgesia are undergoing changes. We herein review the current literature, compare the benefits and disadvantages of the therapeutic options, and make recommendations based on the current literature and clinical experience. PMID:26413222

  8. Obesity and Metabolic Disease After Childhood Cancer.

    PubMed

    Barnea, Dana; Raghunathan, Nirupa; Friedman, Danielle Novetsky; Tonorezos, Emily S

    2015-11-01

    As care for the childhood cancer patient has improved significantly, there is an increasing incidence of treatment-related late effects. Obesity and type 2 diabetes mellitus are common and significant metabolic conditions in some populations of adult survivors of childhood cancer. Results from the Childhood Cancer Survivor Study and other large cohorts of childhood cancer survivors reveal that long-term survivors of acute lymphoblastic leukemia and those who received total body irradiation or abdominal radiotherapy are at highest risk. The potential mechanisms for the observed increase in risk, including alterations in leptin and adiponectin, pancreatic insufficiency, poor dietary habits, sedentary lifestyle, and perhaps changes in the composition of the gut microbiota, are reviewed. Discussion of exercise and diet intervention studies shows that further research about the barriers to a healthy lifestyle and other interventions in childhood cancer survivors is warranted. PMID:26568532

  9. Liver spots

    MedlinePlus

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ...

  10. How Are Childhood Cancers Found?

    MedlinePlus

    ... Topic How are childhood cancers treated? How are childhood cancers found? Screening for childhood cancers Screening is testing for a disease such ... in people who don’t have any symptoms. Childhood cancers are rare, and there are no widely ...

  11. Proteoglycans in liver cancer.

    PubMed

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  12. Proteoglycans in liver cancer

    PubMed Central

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  13. Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity

    PubMed Central

    Halbritter, Jan; Gee, Heon Yung; Porath, Jonathan D.; Lawson, Jennifer A.; Airik, Rannar; Shril, Shirlee; Allen, Susan J.; Stein, Deborah; Al Kindy, Adila; Beck, Bodo B.; Cengiz, Nurcan; Moorani, Khemchand N.; Ozaltin, Fatih; Hashmi, Seema; Sayer, John A.; Bockenhauer, Detlef; Soliman, Neveen A.; Otto, Edgar A.; Lifton, Richard P.; Hildebrandt, Friedhelm

    2015-01-01

    Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering, and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis and allows identification of novel candidate genes. PMID:26489029

  14. Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity.

    PubMed

    Braun, Daniela A; Schueler, Markus; Halbritter, Jan; Gee, Heon Yung; Porath, Jonathan D; Lawson, Jennifer A; Airik, Rannar; Shril, Shirlee; Allen, Susan J; Stein, Deborah; Al Kindy, Adila; Beck, Bodo B; Cengiz, Nurcan; Moorani, Khemchand N; Ozaltin, Fatih; Hashmi, Seema; Sayer, John A; Bockenhauer, Detlef; Soliman, Neveen A; Otto, Edgar A; Lifton, Richard P; Hildebrandt, Friedhelm

    2016-02-01

    Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes. PMID:26489029

  15. Assessing Thai Early Childhood Teachers' Knowledge of Inclusive Education

    ERIC Educational Resources Information Center

    Agbenyega, Joseph S.; Klibthong, Sunanta

    2014-01-01

    An ever-increasing number of children with and without disabilities are attending early childhood programmes and learning together. Early childhood inclusion considers all children with and without disabilities, and their families as full members of the early childhood community. Although many early childhood teachers accept the educational rights…

  16. The combination of conjugated linoleic acid (CLA) and extra virgin olive oil increases mitochondrial and body metabolism and prevents CLA-associated insulin resistance and liver hypertrophy in C57Bl/6 mice.

    PubMed

    Baraldi, Flávia G; Vicentini, Tatiane M; Teodoro, Bruno G; Dalalio, Felipe M; Dechandt, Carlos R P; Prado, Ieda M R; Curti, Carlos; Cardoso, Fernanda C; Uyemura, Sergio A; Alberici, Luciane C

    2016-02-01

    Clinical conditions associated with obesity can be improved by daily intake of conjugated linoleic acid (CLA) or extra virgin olive oil (EVOO). Here we investigated whether dietary supplementation with CLA and EVOO, either alone or in combination, changes body metabolism associated with mitochondrial energetics. Male C57Bl/6 mice were divided into one of four groups: CLA (1:1 cis-9, trans-11:trans-10, cis-12; 18:2 isomers), EVOO, CLA plus EVOO or control (linoleic acid). Each mouse received 3 g/kg body weight of the stated oil by gavage on alternating days for 60 days. Dietary supplementation with CLA, alone or in combination with EVOO: (a) reduced the white adipose tissue gain; (b) increased body VO2 consumption, VCO2 production and energy expenditure; (c) elevated uncoupling protein (UCP)-2 expression and UCP activity in isolated liver mitochondria. This organelle, when energized with NAD(+)-linked substrates, produced high amounts of H2O2 without inducing oxidative damage. Dietary supplementation with EVOO alone did not change any metabolic parameter, but supplementation with CLA itself promoted insulin resistance and elevated weight, lipid content and acetyl-CoA carboxylase-1 expression in liver. Interestingly, the in vivo antioxidant therapy with N-acetylcysteine abolished the CLA-induced rise of body metabolism and liver UCP expression and activity, while the in vitro antioxidant treatment with catalase mitigated the CLA-dependent UCP-2 expression in hepatocytes; these findings suggest the participation of an oxidative-dependent pathway. Therefore, this study clarifies the mechanisms by which CLA induces liver UCP expression and activity, and demonstrates for the first time the beneficial effects of combined CLA and EVOO supplementation. PMID:26878792

  17. Childhood medulloblastoma.

    PubMed

    Massimino, Maura; Biassoni, Veronica; Gandola, Lorenza; Garrè, Maria Luisa; Gatta, Gemma; Giangaspero, Felice; Poggi, Geraldina; Rutkowski, Stefan

    2016-09-01

    Medulloblastoma accounts for 15-20% of childhood nervous system tumours. The risk of dying was reduced by 30% in the last twenty years. Patients are divided in risk strata according to post-surgical disease, dissemination, histology and some molecular features such as WNT subgroup and MYC status. Sixty to 70% of patients older than 3 years are assigned to the average-risk group. High-risk patients include those with disseminated and/or residual disease, large cell and/or anaplastic histotypes, MYC genes amplification. Current and currently planned clinical trials will: (1) evaluate the feasibility of reducing both the dose of craniospinal irradiation and the volume of the posterior fossa radiotherapy (RT) for those patients at low biologic risk, commonly identified as those having a medulloblastoma of the WNT subgroup; (2) determine whether intensification of chemotherapy (CT) or irradiation can improve outcome in patients with high-risk disease; (3) find target therapies allowing tailored therapies especially for relapsing patients and those with higher biological risk. PMID:27375228

  18. [Childhood tuberculosis].

    PubMed

    Hamzaoui, A

    2015-01-01

    Childhood TB is an indication of failing TB control in the community. It allows disease persistence in the population. Mortality and morbidity due to TB is high in children. Moreover, HIV co-infection and multidrug-resistant diseases are as frequent in children as in adults. Infection is more frequent in younger children. Disease risk after primary infection is greatest in infants younger than 2 years. In case of exposure, evidence of infection can be obtained using the tuberculin skin test (TST) or an interferon-gamma assay (IGRA). There is no evidence to support the use of IGRA over TST in young children. TB suspicion should be confirmed whenever possible, using new available tools, particularly in case of pulmonary and lymph node TB. Induced sputum, nasopharyngeal aspiration and fine needle aspiration biopsy provide a rapid and definitive diagnosis of mycobacterial infection in a large proportion of patients. Analysis of paediatric samples revealed higher sensitivity and specificity values of molecular techniques in comparison with the ones originated from adults. Children require higher drugs dosages than adults. Short courses of steroids are associated with TB treatment in case of respiratory distress, bronchoscopic desobstruction is proposed for severe airways involvement and antiretroviral therapy is mandatory in case of HIV infection. Post-exposure prophylaxis in children is a highly effective strategy to reduce the risk of TB disease. The optimal therapy for treatment of latent infection with a presumably multidrug-resistant Mycobacterium tuberculosis strain is currently not known. PMID:24932504

  19. Childhood craniopharyngioma.

    PubMed

    Müller, Hermann L

    2013-03-01

    Craniopharyngiomas (CP) are partly cystic embryogenic malformations of the sellar and parasellar region. With an overall incidence of 0.5-2.0 new cases/million population/year, approximately 30-50 % of all cases represent childhood CP. Typical manifestations at diagnosis are headache, visual impairment, polyuria/polydypsia, growth retardation, puberty development disturbances, and significant weight gain. Therapy of choice in children with favorable tumor localization is complete resection with the intention to maintain optic nerve and hypothalamic-pituitary functions. In children with unfavorable tumor localization (hypothalamic involvement), a limited resection followed by local irradiation is recommended. Although overall surgical survival rates are high (92 %), recurrence after complete resection and progression after incomplete resection are typical post-surgical events. Particularly troublesome for the pediatric patient are the disturbances to their pubescent development and overall growth. Accordingly, the appropriate time point of irradiation after incomplete resection is under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Quality of life is substantially reduced in approximately 50 % of long-term survivors due to sequelae, notably morbid hypothalamic obesity. CP should be recognized as a chronic disease requiring constant monitoring of the early life as well as post-pubescent consequences and appropriate medical resources for treatment in order to provide optimal quality of survival for patients. PMID:22678820

  20. Childhood aphasias.

    PubMed

    Martins, I P

    1997-01-01

    The study of acquired childhood aphasia has shown that the aphasic syndromes found in adults are reproducible in children with identical lesion sites and that some brain areas are essential for aphasia recovery. Besides, language deficits and learning difficulties are very common in the long-term follow-up of those children. This suggests that the adult pattern of cerebral organization for speech is established early in life and alternative organizations have a lasting price. Yet in contradiction with this, children with focal lesions sustained pre- or perinatally do not show developmentally the aphasic syndromes observed in older children and adults. One possible explanation is that the areas responsible for learning a function are different from those subserving that function as a more mature stage of development. Concerning specific language impairment in children, there is a growing evidence that such syndromes are genetically determined, but there is still a missing link between this predisposition and the structural/functional defects underlying them. The finding that these children are often impaired in other areas of mental development indicates that there may be a more basic cognitive defect underlying their language disorders. PMID:9059756

  1. Fusobacterium Liver Abscess

    PubMed Central

    Buelow, Ben D.; Lambert, Joelle M.; Gill, Ryan M.

    2013-01-01

    Fusobacterium is well characterized as an oropharyngeal pathogen that may induce a septic thrombophlebitis by direct extension of abscess into an adjacent neck vessel (Lemierre's syndrome); its potential for visceral abscess formation, however, remains under-recognized. A 65-year-old man with a recent history of multiple rim-enhancing liver lesions presented to the emergency room with fever and abdominal pain. Based on interval increase in the size of the lesions, abscess was suspected. A liver biopsy was performed, and although no organism could be identified on routine microscopy, Warthin-Starry stain revealed Gram-negative bacilli consistent with an anaerobic Fusobacterium species as the underlying etiology of liver abscess formation. Subsequent anaerobic culture results confirmed the diagnosis. This case highlights the importance of consideration for Fusobacterium infection in the setting of liver abscess if anaerobic organisms have not yet been excluded on initial culture evaluation. PMID:24348321

  2. Fusobacterium liver abscess.

    PubMed

    Buelow, Ben D; Lambert, Joelle M; Gill, Ryan M

    2013-01-01

    Fusobacterium is well characterized as an oropharyngeal pathogen that may induce a septic thrombophlebitis by direct extension of abscess into an adjacent neck vessel (Lemierre's syndrome); its potential for visceral abscess formation, however, remains under-recognized. A 65-year-old man with a recent history of multiple rim-enhancing liver lesions presented to the emergency room with fever and abdominal pain. Based on interval increase in the size of the lesions, abscess was suspected. A liver biopsy was performed, and although no organism could be identified on routine microscopy, Warthin-Starry stain revealed Gram-negative bacilli consistent with an anaerobic Fusobacterium species as the underlying etiology of liver abscess formation. Subsequent anaerobic culture results confirmed the diagnosis. This case highlights the importance of consideration for Fusobacterium infection in the setting of liver abscess if anaerobic organisms have not yet been excluded on initial culture evaluation. PMID:24348321

  3. Liver bioengineering

    PubMed Central

    Caralt, Mireia; Velasco, Enrique; Lanas, Angel; Baptista, Pedro M

    2014-01-01

    Liver bioengineering has been a field of intense research and popular excitement in the past decades. It experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization1–3. Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue. Even notable novel strategies that rely on iPSC-derived liver progenitor cells potential to self-organize in association with endothelial cells in hepatic organoids are lacking critical components of the native tissue (e.g., bile ducts, functional vascular network, hepatic microarchitecture, etc)4. Hence, it is vital to understand the strengths and short comes of our current strategies in this quest to re-create liver organogenesis in vitro. To shed some light into these issues, this review describes the different actors that play crucial roles in liver organogenesis and highlights the steps still missing to successfully generate whole livers and hepatic organoids in vitro for multiple applications. PMID:25102189

  4. Neuroimaging of scoliosis in childhood.

    PubMed

    Kim, F M; Poussaint, T Y; Barnes, P D

    1999-02-01

    A curvature abnormality may be the initial or major presenting feature in a child with disease of the spinal column or spinal neuraxis. A simplified classification of common spinal curvature abnormalities of childhood include idiopathic, congenital/dysraphic, skeletal dysplasia, neurofibromatosis, and painful. The great majority of childhood scoliosis falls into the idiopathic category. Atypical clinical or radiographic features in a presumed idiopathic scoliosis may indicate an otherwise occult tumor or hydrosyringomyelia, or may be a consequence of increasing curvature with disk protrusion, nerve impingement, or cord attenuation. Neuroimaging beyond plain films is commonly necessary for atypical idiopathic scoliosis and for the other categories of scoliosis listed. PMID:9974506

  5. Liver transplantation in Ireland.

    PubMed

    Iqbal, Masood; Elrayah, Elgaily A; Traynor, Oscar; McCormick, P Aiden

    2016-07-01

    The Irish National Liver Transplant program commenced in 1993 in St. Vincent's University Hospital in Dublin. It is an adult-only program and is the only liver transplant program in Ireland. Pediatric recipients are referred to King's College Hospital in the United Kingdom. To date, almost 1000 adult liver transplants have been performed. Current 1-year patient survival is 93%, and 5-year survival is 79%. The program is fully funded by the government health service. There is a close collaboration with the United Kingdom Organ Donation and Transplant Directorate, and there is an arrangement for organ sharing for super-urgent transplants. Traditionally, organ donation rates have been high in Ireland. However, demand for liver transplant has increased over the past 20 years, and waiting lists are now lengthening. Deceased cardiac death donation is now being considered, but there are no plans for living related donor liver transplant. Donor coordinators have recently been appointed to the major hospitals in Ireland, and it is hoped that this initiative will lead to an increase in organ donation rates. Liver Transplantation 22 1014-1018 2016 AASLD. PMID:27065358

  6. Health lifestyles in early childhood.

    PubMed

    Mollborn, Stefanie; James-Hawkins, Laurie; Lawrence, Elizabeth; Fomby, Paula

    2014-12-01

    This study integrates two important developments, the concept of health lifestyles (which has focused on adults and adolescents) and the increased attention to early childhood. We introduce the concept of children's health lifestyles, identifying differences from adult health lifestyles and articulating intergenerational transmission and socialization processes shaping children's health lifestyles. Using the nationally representative Early Childhood Longitudinal Study-Birth Cohort (2001-2007; N ≈ 6,150), latent class analyses identify predominant health lifestyles among U.S. preschoolers. Five distinct empirical patterns representing health lifestyles emerge, two capturing low and medium levels of overall risk across domains and three capturing domain-specific risks. Social background predicts children's health lifestyles, but lower household resources often explain these relationships. Across kindergarten measures of cognition, behavior, and health, preschool health lifestyles predict children's development even after controlling for social disadvantage and concurrent household resources. Further research on health lifestyles throughout childhood is warranted. PMID:25413801

  7. Tooth decay - early childhood

    MedlinePlus

    Bottle mouth; Bottle carries; Baby bottle tooth decay; Early childhood caries (ECC) ... chap 304. Ribeiro NM, Ribeiro MA. Breastfeeding and early childhood caries: a critical review. J Pediatr (Rio J) . ...

  8. Stages of Childhood Rhabdomyosarcoma

    MedlinePlus

    ... risk rhabdomyosarcoma. The following risk groups are used: Low-risk childhood rhabdomyosarcoma Low-risk childhood rhabdomyosarcoma is ... therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to ...

  9. Childhood Brain Tumors

    MedlinePlus

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  10. Childhood Interstitial Lung Disease

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Childhood Interstitial Lung Disease? Childhood interstitial (in-ter-STISH-al) lung disease, ... with similar symptoms—it's not a precise diagnosis. Interstitial lung disease (ILD) also occurs in adults. However, the cause ...

  11. What Is Childhood Leukemia?

    MedlinePlus

    ... key statistics for childhood leukemia? What is childhood leukemia? Cancer starts when cells start to grow out ... start making antibodies to fight them. Types of leukemia in children Leukemia is often described as being ...

  12. Childhood Brain Tumors

    MedlinePlus

    ... They are among the most common types of childhood cancers. Some are benign tumors, which aren't ... can still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches ...

  13. Liver Regeneration

    PubMed Central

    Michalopoulos, George K.

    2009-01-01

    Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other. PMID:17559071

  14. Early Childhood Intervention in China

    ERIC Educational Resources Information Center

    Zheng, Yuzhu; Maude, Susan P.; Brotherson, Mary Jane

    2015-01-01

    With rapid economic development and increasing awareness of the importance of early childhood intervention (ECI), China is re-examining its social and educational practices for young children with disabilities. This re-examination may have a significant impact on young children with disabilities in China. It may also set an example for other…

  15. Childhood cancer: A growing problem.

    PubMed Central

    Schmidt, C W

    1998-01-01

    Childhood cancer is the leading cause of disease-related death among children in the United States,and rates are increasing by approximately 1% each year. Unfortunately,the science of epidemiology has not provided definitive answers to the question of why cancer strikes children. PMID:9422708

  16. What Is Liver Cancer?

    MedlinePlus

    ... Topic Key statistics about liver cancer What is liver cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  17. Benign Liver Tumors

    MedlinePlus

    ... Search: Your Liver Liver Health and Wellness Recipes Liver Disease Information Patients & Families Caregiver's FAQ Become an Organ ... 2013 Liver Awareness Month Personal Story - David Roncori Liver Disease - The Big Picture 13 Ways to a Healthy ...

  18. Different-Sized Gold Nanoparticle Activator/Antigen Increases Dendritic Cells Accumulation in Liver-Draining Lymph Nodes and CD8+ T Cell Responses.

    PubMed

    Zhou, Qianqian; Zhang, Yulong; Du, Juan; Li, Yuan; Zhou, Yong; Fu, Qiuxia; Zhang, Jingang; Wang, Xiaohui; Zhan, Linsheng

    2016-02-23

    The lack of efficient antigen and activator delivery systems, as well as the restricted migration of dendritic cells (DCs) to secondary lymph organs, dramatically limits DC-based adoptive immunotherapy. We selected two spherical gold nanoparticle (AuNP)-based vehicles of optimal size for activator and antigen delivery. Their combination (termed the NanoAu-Cocktail) was associated with the dual targeting of CpG oligonucleotides (CpG-ODNs) and an OVA peptide (OVAp) to DC subcellular compartments, inducing enhanced antigen cross-presentation, upregulated expression of costimulatory molecules and elevated secretion of T helper1 cytokines. We demonstrated that the intravenously transfused NanoAu-Cocktail pulsed DCs showed dramatically improved in vivo homing ability to lymphoid tissues and were settled in T cell area. Especially, by tissue-distribution analysis, we found that more than 60% of lymphoid tissues-homing DCs accumulated in liver-draining lymph nodes (LLNs). The improved homing ability of NanoAu-Cocktail pulsed DCs was associated with the high expression of chemokine receptor 7 (CCR7) and rearrangement of the cytoskeletons. In addition, by antigen-specific tetramers detection, NanoAu-Cocktail pulsed DCs were proved able to elicit strong antigen-specific CD8+ T cell responses, which provided enhanced protection from viral invasions. This study highlights the importance of codelivering antigen/adjuvant using different sized gold nanoparticles to improve DC homing and therapy. PMID:26771692

  19. The TERT promoter SNP rs2853669 decreases E2F1 transcription factor binding and increases mortality and recurrence risks in liver cancer.

    PubMed

    Ko, Eunkyong; Seo, Hyun-Wook; Jung, Eun Sun; Kim, Baek-hui; Jung, Guhung

    2016-01-01

    A common single-nucleotide polymorphism in the telomerase reverse transcriptase (TERT) promoter, rs2853669 influences patient survival rates and the risk of developing cancer. Recently, several lines of evidence suggest that the rs2853669 suppresses TERT promoter mutation-mediated TERT expression levels and cancer mortality as well as recurrence rates. However, no reports are available on the impact of rs2853669 on TERT expression in hepatocellular carcinoma (HCC) and its association with patient survival. Here, we found that HCC-related overall and recurrence-free survival rates were not associated with TERT promoter mutation individually, but rs2853669 and the TERT promoter mutation in combination were associated with poor survival rates. TERT mRNA expression and telomere fluorescence levels were greater in patients with HCC who had both the combination. The combination caused TERT promoter methylation through regulating the binding of DNA methyltransferase 1 and histone deacetylase 1 to the TERT promoter in HCC cell lines. The TERT expression level was significantly higher in HCC tumor with a methylated promoter than in that with an unmethylated promoter. In conclusion, we demonstrate a substantial role for the rs2853669 in HCC with TERT promoter mutation, which suggests that the combination of the rs2853669 and the mutation indicate poor prognoses in liver cancer. PMID:26575952

  20. The TERT promoter SNP rs2853669 decreases E2F1 transcription factor binding and increases mortality and recurrence risks in liver cancer

    PubMed Central

    Ko, Eunkyong; Seo, Hyun-Wook; Jung, Eun Sun; Kim, Baek-hui; Jung, Guhung

    2016-01-01

    A common single-nucleotide polymorphism in the telomerase reverse transcriptase (TERT) promoter, rs2853669 influences patient survival rates and the risk of developing cancer. Recently, several lines of evidence suggest that the rs2853669 suppresses TERT promoter mutation-mediated TERT expression levels and cancer mortality as well as recurrence rates. However, no reports are available on the impact of rs2853669 on TERT expression in hepatocellular carcinoma (HCC) and its association with patient survival. Here, we found that HCC-related overall and recurrence-free survival rates were not associated with TERT promoter mutation individually, but rs2853669 and the TERT promoter mutation in combination were associated with poor survival rates. TERT mRNA expression and telomere fluorescence levels were greater in patients with HCC who had both the combination. The combination caused TERT promoter methylation through regulating the binding of DNA methyltransferase 1 and histone deacetylase 1 to the TERT promoter in HCC cell lines. The TERT expression level was significantly higher in HCC tumor with a methylated promoter than in that with an unmethylated promoter. In conclusion, we demonstrate a substantial role for the rs2853669 in HCC with TERT promoter mutation, which suggests that the combination of the rs2853669 and the mutation indicate poor prognoses in liver cancer. PMID:26575952

  1. Health Behaviors of Childhood Cancer Survivors

    PubMed Central

    Ford, Jennifer S.; Barnett, Marie; Werk, Rachel

    2014-01-01

    There has been a dramatic increase in the number of childhood cancer survivors living to an old age due to improved cancer treatments. However, these survivors are at risk of numerous late effects as a result of their cancer therapy. Engaging in protective health behaviors and limiting health damaging behaviors are vitally important for these survivors given their increased risks. We reviewed the literature on childhood cancer survivors’ health behaviors by searching for published data and conference proceedings. We examine the prevalence of a variety of health behaviors among childhood cancer survivors, identify significant risk factors, and describe health behavior interventions for survivors.

  2. Liver xenotransplantation.

    PubMed

    Marino, I R; Tzakis, A G; Fung, J J; Todo, S; Doyle, H R; Manez, R; Starzl, T E

    1993-10-01

    During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure. PMID:25951555

  3. Liver cirrhosis.

    PubMed Central

    Williams, E. J.; Iredale, J. P.

    1998-01-01

    Liver fibrosis and its related complications continue to represent a significant worldwide healthcare burden. Over the past decade there has been considerable improvement in our understanding of the cellular mechanisms and pathophysiology underlying hepatic fibrosis. This greater insight into the relevant basic sciences may lead to the development of novel treatment strategies designed to block the fibrogenic cascade or even enhance matrix degradation. In addition, there have been significant advances in the management of the complications of cirrhosis, with specific treatments now available for some conditions. Perhaps most notably, liver transplantation is now a highly successful treatment for end-stage liver disease and should be considered in all patients with chronic liver disease. PMID:9683971

  4. Liver transplant

    MedlinePlus

    Risks for any anesthesia are: Problems breathing Reactions to medications Risks for any surgery are: Bleeding Heart attack or stroke Infection Liver transplant surgery and management after surgery carry major risks. There is ...

  5. How robust is the evidence of an emerging or increasing female excess in physical morbidity between childhood and adolescence? Results of a systematic literature review and meta-analyses

    PubMed Central

    MacLean, Alice; Sweeting, Helen; Egan, Matt; Der, Geoff; Adamson, Joy; Hunt, Kate

    2013-01-01

    For asthma and psychological morbidity, it is well established that higher prevalence among males in childhood is replaced by higher prevalence among females by adolescence. This review investigates whether there is evidence for a similar emerging female ‘excess’ in relation to a broad range of physical morbidity measures. Establishing whether this pattern is generalised or health outcome-specific will further understandings of the aetiology of gender differences in health. Databases (Medline; Embase; CINAHL; PsycINFO; ERIC) were searched for English language studies (published 1992–2010) presenting physical morbidity prevalence data for males and females, for at least two age-bands within the age-range 4–17 years. A three-stage screening process (initial sifting; detailed inspection; extraction of full papers), was followed by study quality appraisals. Of 11 245 identified studies, 41 met the inclusion criteria. Most (n = 31) presented self-report survey data (five longitudinal, 26 cross-sectional); 10 presented routinely collected data (GP/hospital statistics). Extracted data, supplemented by additional data obtained from authors of the included studies, were used to calculate odds ratios of a female excess, or female:male incident rate ratios as appropriate. To test whether these changed with age, the values were logged and regressed on age in random effects meta-regressions. These showed strongest evidence of an emerging/increasing female excess for self-reported measures of headache, abdominal pain, tiredness, migraine and self-assessed health. Type 1 diabetes and epilepsy, based on routinely collected data, did not show a significant emerging/increasing female excess. For most physical morbidity measures reviewed, the evidence broadly points towards an emerging/increasing female excess during the transition to adolescence, although results varied by morbidity measure and study design, and suggest that this may occur at a younger age than previously

  6. Developmental Pathways from Parental Substance Use to Childhood Academic Achievement

    PubMed Central

    Brook, Judith S.; Saar, Naomi S.; Brook, David W.

    2010-01-01

    This cross-sectional study examined the pathways to childhood academic achievement in 209 African American and Puerto Rican children and their mothers. There were three pathways to childhood academic achievement: (a) the mother-child relationship and the child’s personality mediated between parental substance use and childhood academic achievement; (b) the child’s personality mediated between parental education and childhood academic achievement; and (c) there was a direct relationship between the child’s gender and childhood academic achievement. Policy and clinical implications suggest the importance of increasing educational opportunities for all parents, providing substance use treatment and self-esteem workshops, and altering the school curriculum. PMID:20525035

  7. [Liver intervention].

    PubMed

    Oi, H

    2000-12-01

    Interventional radiology is now widely performed for the treatment of liver tumors, because surgery is sometimes limited by poor liver function. Transcatheter arterial chemoembolization(TACE) is an effective therapy for hepatocellular carcinoma. Lipiodol TACE shows a strong antitumor effect because of the overflow of excess iodized oil into the portal veins, and segmental TACE is recommended to avoid deteriorating liver function. Selective CT arteriography is performed in order to decide on the treatment area, and TACE under CT guidance leads to effective results in terms of dense accumulation of the chemotherapeutic drug in the individual tumors that are affected by the ischemic state and anticancer drugs. Percutaneous microwave or radiofrequency coagulation therapy is adequate for a few of the hypovascular tumors. Excessive coagulation through the needle tract is indispensable in these therapies, and precisely designed puncture is necessary to minimize damage to the liver parenchyma. Selective chemotherapy to the tumor-bearing organ is the first step in a number of liver tumors. Continuous intra-arterial infusion chemotherapy is performed for multiple liver metastases. The reservoir implantation technique is percutaneously achieved via the left subclavian artery under ultrasound guidance, without the exposure of an artery in the incision method, which can induce thrombus formation. PMID:11197832

  8. Pediatric non-alcoholic fatty liver disease: New insights and future directions

    PubMed Central

    Marzuillo, Pierluigi; del Giudice, Emanuele Miraglia; Santoro, Nicola

    2014-01-01

    One of the most common complications of childhood obesity is the non-alcoholic fatty liver disease (NAFLD), which is the most common form of liver disease in children. NAFLD is defined by hepatic fat infiltration > 5% hepatocytes, as assessed by liver biopsy, in the absence of excessive alcohol intake, viral, autoimmune and drug-induced liver disease. It encompasses a wide spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis, which, in turn, can evolve into cirrhosis and end stage liver disease. Obesity and insulin resistance are the main risk factors for pediatric NAFLD. In fact, NAFLD is strongly associated with the clinical features of insulin resistance especially the metabolic syndrome, prediabetes and type 2 diabetes mellitus (T2D). In particular, it has been clearly shown in obese youth that the prevalence of metabolic syndrome, pre-diabetes and type 2 diabetes increases with NAFLD severity progression. Evidence that not all of the obese patients develop NAFLD suggests that the disease progression is likely to depend on complex interplay between environmental factors and genetic predisposition. Recently, a non-synonymous SNP (rs738409), characterized by a C to G substitution encoding an isoleucine to methionine substitution at the amino acid position 148 in the patatin like phospholipase containing domain 3 gene (PNPLA3), has been associated with hepatic steatosis in a multiethnic cohort of adults as well as in children. Another important polymorphisms that acts with PNPLA3 to convey susceptibility to fatty liver in obese youths is the rs1260326 polymorphism in the glucokinase regulatory protein. The pharmacological approach in NAFLD children poorly adherent to or being unresponsive/partially responsive to lifestyle changes, is aimed at acting upon specific targets involved in the pathogenesis. There are some therapeutic approaches that are being studied in children. This article reviews the current knowledge regarding

  9. Childhood Gender Nonconformity: A Risk Indicator for Childhood Abuse and Posttraumatic Stress in Youth

    PubMed Central

    Rosario, Margaret; Corliss, Heather L.; Koenen, Karestan C.; Austin, S. Bryn

    2012-01-01

    OBJECTIVES: Childhood gender nonconformity has been associated with poorer relationships with parents, but it is unknown if childhood gender nonconformity is associated with childhood abuse or risk of posttraumatic stress disorder (PTSD) in youth. METHODS: We examined whether gender nonconformity before age 11 years was associated with childhood sexual, physical, and psychological abuse and lifetime risk of probable PTSD by using self-report questionnaire data from the 2007 wave of the Growing Up Today Study (n = 9864, mean age = 22.7 years), a longitudinal cohort of US youth. We further examined whether higher exposure to childhood abuse mediated possible elevated prevalence of PTSD in nonconforming children. Finally, we examined whether association of childhood gender nonconformity with PTSD was independent of sexual orientation. RESULTS: Exposure to childhood physical, psychological, and sexual abuse, and probable PTSD were elevated in youth in the top decile of childhood gender nonconformity compared with youth below median nonconformity. Abuse victimization disparities partly mediated PTSD disparities by gender nonconformity. Gender nonconformity predicted increased risk of lifetime probable PTSD in youth after adjustment for sexual orientation. CONCLUSIONS: We identify gender nonconformity as an indicator of children at increased risk of abuse and probable PTSD. Pediatricians and school health providers should consider abuse screening for this vulnerable population. Further research to understand how gender nonconformity might increase risk of abuse and to develop family interventions to reduce abuse risk is needed. PMID:22351893

  10. Childhood obesity: causes and consequences.

    PubMed

    Sahoo, Krushnapriya; Sahoo, Bishnupriya; Choudhury, Ashok Kumar; Sofi, Nighat Yasin; Kumar, Raman; Bhadoria, Ajeet Singh

    2015-01-01

    Childhood obesity has reached epidemic levels in developed as well as in developing countries. Overweight and obesity in childhood are known to have significant impact on both physical and psychological health. Overweight and obese children are likely to stay obese into adulthood and more likely to develop non-communicable diseases like diabetes and cardiovascular diseases at a younger age. The mechanism of obesity development is not fully understood and it is believed to be a disorder with multiple causes. Environmental factors, lifestyle preferences, and cultural environment play pivotal roles in the rising prevalence of obesity worldwide. In general, overweight and obesity are assumed to be the results of an increase in caloric and fat intake. On the other hand, there are supporting evidence that excessive sugar intake by soft drink, increased portion size, and steady decline in physical activity have been playing major roles in the rising rates of obesity all around the world. Childhood obesity can profoundly affect children's physical health, social, and emotional well-being, and self esteem. It is also associated with poor academic performance and a lower quality of life experienced by the child. Many co-morbid conditions like metabolic, cardiovascular, orthopedic, neurological, hepatic, pulmonary, and renal disorders are also seen in association with childhood obesity. PMID:25949965

  11. Cardiovascular consequences of childhood obesity.

    PubMed

    McCrindle, Brian W

    2015-02-01

    Childhood and adolescent overweight and obesity is an important and increasingly prevalent public health problem in Canada and worldwide. High adiposity in youth is indicated in clinical practice by plotting body mass index on appropriate percentile charts normed for age and sex, although waist measures might be a further tool. High adiposity can lead to adiposopathy in youth, with associated increases in inflammation and oxidative stress, changes in adipokines, and endocrinopathy. This is manifest as cardiometabolic risk factors in similar patterns to those in noted in obese adults. Obesity and cardiometabolic risk factors have been shown to be associated with vascular changes indicative of early atherosclerosis, and ventricular hypertrophy, dilation, and dysfunction. These cardiovascular consequences are evident in youth, but childhood obesity is also predictive of similar consequences in adulthood. Childhood obesity and risk factors have been shown to track into adulthood and worsen in most individuals. The result is an exponential acceleration of atherosclerosis, which can be predicted to translate into an epidemic of premature cardiovascular disease and events. A change in paradigm is needed toward preventing and curing atherosclerosis and not just preventing cardiovascular disease. This would necessarily create an imperative for preventing and treating childhood obesity. Urgent attention, policy, and action are needed to avoid the enormous future social and health care costs associated with the cardiovascular consequences of obesity in youth. PMID:25661547

  12. Childhood obesity: causes and consequences

    PubMed Central

    Sahoo, Krushnapriya; Sahoo, Bishnupriya; Choudhury, Ashok Kumar; Sofi, Nighat Yasin; Kumar, Raman; Bhadoria, Ajeet Singh

    2015-01-01

    Childhood obesity has reached epidemic levels in developed as well as in developing countries. Overweight and obesity in childhood are known to have significant impact on both physical and psychological health. Overweight and obese children are likely to stay obese into adulthood and more likely to develop non-communicable diseases like diabetes and cardiovascular diseases at a younger age. The mechanism of obesity development is not fully understood and it is believed to be a disorder with multiple causes. Environmental factors, lifestyle preferences, and cultural environment play pivotal roles in the rising prevalence of obesity worldwide. In general, overweight and obesity are assumed to be the results of an increase in caloric and fat intake. On the other hand, there are supporting evidence that excessive sugar intake by soft drink, increased portion size, and steady decline in physical activity have been playing major roles in the rising rates of obesity all around the world. Childhood obesity can profoundly affect children's physical health, social, and emotional well-being, and self esteem. It is also associated with poor academic performance and a lower quality of life experienced by the child. Many co-morbid conditions like metabolic, cardiovascular, orthopedic, neurological, hepatic, pulmonary, and renal disorders are also seen in association with childhood obesity. PMID:25949965

  13. Liver-Regenerative Transplantation: Regrow and Reset.

    PubMed

    Collin de l'Hortet, A; Takeishi, K; Guzman-Lepe, J; Handa, K; Matsubara, K; Fukumitsu, K; Dorko, K; Presnell, S C; Yagi, H; Soto-Gutierrez, A

    2016-06-01

    Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)-derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS-derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation. PMID:26699680

  14. Liver-Regenerative Transplantation: Regrow and Reset

    PubMed Central

    de l’Hortet, A. Collin; Takeishi, K.; Guzman-Lepe, J.; Handa, K.; Matsubara, K.; Fukumitsu, K.; Dorko, K.; Presnell, S. C.; Yagi, H.; Soto-Gutierrez, A.

    2016-01-01

    Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)–derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS-derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation. PMID:26699680

  15. Adiponectin in childhood.

    PubMed

    Jeffery, Alison N; Murphy, Michael J; Metcalf, Brad S; Hosking, Joanne; Voss, Linda D; English, Patrick; Sattar, Naveed; Wilkin, Terence J

    2008-01-01

    Adiponectin, a hormone produced and secreted by adipocytes, is present in circulation in high circulating concentrations, suggesting an important physiological role. An indirect regulator of glucose metabolism, adiponectin increases insulin sensitivity, improves glucose tolerance and inhibits inflammation. Plasma adiponectin relates inversely to adiposity and, importantly, reflects the sequelae of accumulation of excess adiposity. The role of adiponectin in adults has been explored in detail. Studies in children are now available and, given the increasing rates of childhood obesity, it is important to establish the role of adiponectin in mediating insulin resistance and cardiovascular disease in this age group. This paper reviews the regulation of adiponectin, its effect on body mass, glucose metabolism and cardiovascular risk in infants, children and adolescents. It demonstrates clear links between adiponectin and features of the metabolic syndrome in obese children and adolescents. However, adiponectin's role as a predictor of metabolic dysfunction in healthy, normal-weight youngsters is less clear. PMID:19086185

  16. Brain development in childhood.

    PubMed

    Taki, Yasuyuki; Kawashima, Ryuta

    2012-01-01

    Although human brain development continues throughout childhood and adolescence, it is a non-linear process both structurally and functionally. Here we review studies of brain development in healthy children from the viewpoint of structure and the perfusion of gray and white matter. Gray matter volume increases and then decreases with age, with the developmental time of the peak volume differing among brain regions in the first and second decades of life. On the other hand, white matter volume increase is mostly linear during those periods. As regards fractional anisotropy, most regions show an exponential trajectory with aging. In addition, cerebral blood flow and gray matter volume are proportional at similar developmental ages. Moreover, we show that several lifestyle choices, such as sleeping habits and breakfast staple, affect gray matter volume in healthy children. There are a number of uninvestigated important issues that require future study. PMID:23166579

  17. Disorders of childhood growth and development: childhood obesity.

    PubMed

    Mendez, Robert; Grissom, Maureen

    2013-07-01

    The incidence of childhood obesity in the United States is estimated at 17%, or 12 million children ages 2 to 19 years. Obesity is a multifactorial condition with syndromic and nonsyndromic variants. Genetic, social, ethnic, endocrinologic, and behavioral issues are all potential etiologic factors. Preventive efforts should begin with monitoring from birth and include breastfeeding until age 6 months, avoiding juices, and promoting fruit and vegetable consumption and adequate exercise. Childhood obesity is diagnosed based on body mass index; a child is considered overweight at the 85th to 95th percentiles and obese at or above the 95th percentile. After obesity is diagnosed, testing should include blood pressure levels, fasting lipid profile, diabetes screening, and liver function tests. The physician should obtain a detailed history of the physical activity level and food intake and assess possible complications of obesity, including depression and hypertension, annually. Lifestyle interventions with family involvement are the mainstay of management, with pharmacotherapy or bariatric surgery considered for adolescents only if intensive lifestyle modifications have failed and in the presence of comorbidities. Intervention by multiple disciplines (ie, medicine, nutrition, psychology) is recommended, and family physicians are encouraged to become more involved in encouraging physical activity and improved nutrition for children. PMID:23869391

  18. Cholelithiasis and Cholecystitis in Childhood

    PubMed Central

    Wingert, Willis A.; Mikity, Victor G.

    1967-01-01

    Six cases of cholecystitis and cholelithiasis confirmed by x-ray examination and surgical operation were observed in a ten-year period. Due to the wide variability in signs and symptoms in children, cholecystitis and cholelithiasis can be diagnosed only with a high degree of clinical suspicion and roentgenological examination. Gallbladder disease is uncommon in childhood but should be considered in children with vague abdominal pains or bouts of unexplained jaundice. If a normal appendix is found at laparotomy in the “acute abdomen,” the surgeon would be wise to palpate other specific organs within the abdomen, including the liver and gallbladder. The treatment of choice is cholecystectomy. The prognosis for recovery is excellent if there is no complicating systemic disease. ImagesFigure 1.Figure 2.Figure 3. PMID:6045485

  19. Obesity and liver transplantation

    PubMed Central

    Ayloo, Subhashini; Armstrong, John; Hurton, Scott; Molinari, Michele

    2015-01-01

    The percentage of overweight and obese patients (OPs) waiting for a liver transplant continues to increase. Despite the significant advances occurred in bariatric medicine, obesity is still considered a relative contraindication to liver transplantation (LT). The main aim of this review is to appraise the literature on the outcomes of OPs undergoing LT, treatments that might reduce their weight before, during or after surgery, and discuss some of the controversies and limitations of the current knowledge with the intent of highlighting areas where future research is needed. PMID:26421262

  20. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. Hepatocellular ...

  1. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. ...

  2. Liver disease - resources

    MedlinePlus

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...

  3. Tests for Liver Cancer

    MedlinePlus

    ... cancer Next Topic Liver cancer stages Tests for liver cancer If you have some of the signs ... cancer has come back (recurred). Other blood tests Liver function tests (LFTs): Because liver cancer often develops ...

  4. Liver transplant - series (image)

    MedlinePlus

    The liver is in the right upper abdomen. The liver serves many functions, including the detoxification of substances delivered ... A liver transplant may be recommended for: liver damage due to alcoholism (Alcoholic cirrhosis) primary biliary cirrhosis long-term ( ...

  5. Childhood tuberculosis.

    PubMed

    Jacobs, R F; Eisenach, K D

    1993-01-01

    The dramatic resurgence and increase in the total number of cases of tuberculous infection and disease in children is alarming in the United States. With poverty, poor access to health care, overcrowding (predominantly in inner-city areas), and an increase in immigration from areas with high endemic rates of tuberculosis, the problem in children will continue to increase. If the impact of coinfection with HIV and M. tuberculosis becomes significant, as it has in adults in the United States, this increase in the total number of cases of tuberculous disease could be staggering. The impact of multiple drug-resistant strains of M. tuberculosis and the current crises in availability of effective antituberculous drugs will need to undergo basic and clinical research. Although the possibility for eradication of M. tuberculosis as a human pathogen in the United States still exists, clinicians must reeducate themselves regarding the epidemiology, pathophysiology, diagnostic work-up, and effective treatment of children with tuberculosis in the current situation of increasing tuberculous disease and resistant organisms in children. PMID:8217004

  6. Physical Activity Is Prospectively Associated With Adolescent Nonalcoholic Fatty Liver Disease

    PubMed Central

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

    2016-01-01

    ABSTRACT Objectives: The aim of the present study was to assess whether objectively measured physical activity at mean ages 12 and 14 years are prospectively associated with ultrasound scan liver fat and stiffness (alanine aminotransferase, aspartate aminotransferase [AST], and γ-glutamyl transferase [GGT]) assessed at mean age 17.8 years. Methods: Participants were from the Avon Longitudinal Study of Parents and Children. Total physical activity (counts per minute) and minutes of moderate to vigorous physical activity (MVPA) were measured using ActiGraph accelerometers at mean ages 12 and 14 years. Results: Greater total physical activity and MVPA at ages 12 and 14 years were associated with lower odds of liver fat and lower GGT levels at mean age 17.8 years, such as per 15-minute increase in daily MVPA at age 12 years, the confounder adjusted odds ratio of liver fat was 0.47 (95% confidence interval [CI] 0.27–0.84). Associations attenuated after additional adjustment for fat mass as a potential confounder (eg, per 15-minute increase in daily MVPA at age 12 years, the odds ratio of liver fat attenuated to 0.65 [95% CI 0.35–1.21]) or a potential mediator (eg, per 15-minute increase in daily MVPA at age 12 years the odds ratio of liver fat attenuated to 0.59 [95% CI 0.32–1.09]). Results did not further attenuate after additional adjustment for insulin resistance. There was some evidence that greater total physical activity and MVPA at age 12 years were associated with the higher AST levels. Conclusions: Adolescents who were more active in childhood have lower odds of fatty liver and lower GGT levels. These findings are likely to be, at least in part, explained by adiposity. PMID:26252921

  7. Childhood Overweight and Obesity

    MedlinePlus

    ... Resources & Publications Reports Prevention Strategies & Guidelines Fact Sheets Social Media Tools ... now affects 1 in 6 children and adolescents in the United States. Childhood Obesity Facts How ...

  8. Liver transplantation in Germany.

    PubMed

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD. PMID:27082951

  9. Current Issues in Liver Transplantation

    PubMed Central

    2016-01-01

    The state of liver transplantation continues to evolve. This article focuses on 3 separate yet important issues within this field. First, there is a proposal to change the allocation of donor livers in the United States. The fundamental premise of this proposal is to equalize access to donor livers across the country. To accomplish this goal, the proposal is to increase the geographic area of liver allocation. As might be expected, there is a great deal of controversy surrounding the possibility of a major change in liver allocation and distribution. A second area of interest, and perhaps the most important therapeutic breakthrough in the field of hepatology, is the introduction of direct-acting antiviral agents against hepatitis C virus (HCV) infection. With cure rates up to 100%, an increasing proportion of liver transplant candidates and recipients are being cured of HCV infection with therapies that have minimal side effects. Consequently, the impact of HCV infection on patient and graft survival will likely improve substantially over the next few years. Finally, this article reviews the role of donor-specific antibodies (DSAs) in antibody-mediated rejection. Long recognized as an important factor in graft survival in renal transplantation, DSAs have recently been shown to be a strong predictor of graft and patient survival in liver transplantation. However, the importance of DSAs in liver transplantation is uncertain, in large part due to the absence of proven therapies. PMID:27231452

  10. Pediatric liver transplant for urea cycle disorders and organic acidemias: United Network for Organ Sharing (UNOS) data 2002–2012

    PubMed Central

    Perito, Emily R.; Rhee, Sue; Roberts, John Paul; Rosenthal, Philip

    2013-01-01

    Background Decision-making about liver transplant is unique in children with urea cycle disorders (UCD) and organic acidemias (OA) because of immediate high priority on the waiting list, not related to severity of disease. There is limited national outcomes data on which to base recommendations about liver transplant for UCD or OA. Methods Retrospective analysis of UNOS data on liver recipients <18 years, transplanted 2002–12. Repeat transplants excluded. Results 5.4% of pediatric liver transplants were liver-only for UCD/OA. UCD/OA increased from 4.3% of transplants in 2002–05 to 7.4% in 2010–12 (p<0.0001). 96% were deceased donor. Of these, 59% were transplanted at <2 years of age. Graft survival improved as age at transplant increased (p=0.04). By 5 years post-transplant, graft survival was 78% for children <2 years at transplant and 88% for those ≥2 years (p=0.06). Vascular thrombosis caused 45% of graft losses; 65% in children <2 years. Patient survival also improved as age at transplant increased; 5-year patient survival was 88% in UCD/OA children <2 years at transplant and 99% in those ≥2 years (p=0.006). At last-follow up (54 ± 34.4 months), children transplanted for UCD/OA were more likely to have cognitive and motor delay than those transplanted for other indications. Cognitive and motor delay in UCD/OA children were associated with metabolic disorder but not predicted by age or weight at transplant, gender, ethnicity, split vs. whole liver, or hospitalization at transplant in univariate and multivariate analysis. Conclusion Most liver transplants for UCD/OA occur in early childhood. Further research is needed on the benefits of early transplant for UCD/OA, as younger age may increase post-transplant morbidity. PMID:24136671

  11. Childhood asthma.

    PubMed Central

    Clark, N M; Brown, R W; Parker, E; Robins, T G; Remick, D G; Philbert, M A; Keeler, G J; Israel, B A

    1999-01-01

    Asthma prevalence in children has increased 58% since 1980. Mortality has increased by 78%. The burden of the disease is most acute in urban areas and racial/ethnic minority populations. Hospitalization and morbidity rates for nonwhites are more than twice those for whites. Asthma is characterized by recurrent wheezing, breathlessness, chest tightness, and coughing. Research in the past decade has revealed the importance of inflammation of the airways in asthma and clinical treatment to reduce chronic inflammation. Asthma is associated with production of IgE to common environmental allergens including house dust mite, animal dander, cockroach, fungal spores, and pollens. Some interventions to reduce symptoms through control of dust mite and animal dander have had positive results. Control of symptoms through interventions to reduce exposures to cockroach antigen has not been reported. Studies illustrating causal effects between outdoor air pollution and asthma prevalence are scant. Increases in asthma prevalence have occurred at the same time as general improvements in air quality. However, air quality appears to exacerbate symptoms in the child who already has the disease. Decreased pulmonary function has been associated with exposure to particulates and bronchial hyperresponsiveness to smoke, SO(2) and NO(2). Symptoms have been correlated with increased levels of respirable particulates, ozone, and SO(2). Interventions that reduce the negative outcomes in asthma associated with outdoor environmental factors have not been reported. Control of asthma in children will entail the collaborative efforts of patients, family, clinical professionals, and school personnel, as well as community-wide environmental control measures and conducive national and local policies based on sound research. Images Figure 1 PMID:10423388

  12. An Evaluation of Partnerships for Early Childhood Mental Health

    ERIC Educational Resources Information Center

    Shamblin, Sherry R.

    2013-01-01

    Early Childhood Mental Health Consultation (ECMHC) has been linked to increased teacher competence and efficacy, as well as increased social skills and decreased challenging behaviors for participating children (Green, 2009). Partnerships for Early Childhood Mental Health ("Partnerships") is an ECMHC program in Southeastern Ohio. This…

  13. The Progression and Natural History of Pediatric Nonalcoholic Fatty Liver Disease.

    PubMed

    Goyal, Nidhi P; Schwimmer, Jeffrey B

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. Childhood NAFLD is associated with hepatic and nonhepatic morbidity and mortality. Nonhepatic associations include cardiovascular, metabolic, pulmonary, and psychological disorders. Cardiovascular conditions observed in childhood include left ventricular dysfunction. Furthermore, childhood obesity is associated with greater odds of having hepatocellular carcinoma as an adult. Evidence suggests that NAFLD may begin in utero in children of diabetic mothers. Thus rigorous efforts for structured diagnosis and follow-up are a priority to better develop the understanding of outcomes in pediatric NAFLD. PMID:27063272

  14. Treatment of mice with 2,3,7,8-Tetrachlorodibenzo-p-dioxin markedly increases the levels of a number of cytochrome P450 metabolites of omega-3 polyunsaturated fatty acids in the liver and lung

    PubMed Central

    Yang, J.; Solaimani, P.; Dong, H; Hammock, B.D.; Hankinson, O.

    2014-01-01

    We previously reported that 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increased the levels of several cytochrome P450 metabolites of the omega-6 polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA) and linoleic acid in the serum, liver, lung and spleen of C57BL/6 mice in an aryl hydrocarbon receptor (AHR)-dependent fashion. These increases correlated with increased levels of CYP1A1, CYP1A2 and/or CYP1B1. In the current study, we measured 77 oxylipins, including 59 that we had not measured previously, and demonstrate that TCDD also markedly increases the levels of many epoxide and diol metabolites of the omega-3 PUFAs, α-linolenic acid, eicosapentaenoic acid (EPA) and docasahexaenoic acid (DHA) in these mice. Since these epoxide metabolites have been reported to have opposite effects on angiogenesis, tumor growth and tumor metastasis compared with the equivalent metabolites of omega-6 PUFA, these observations have important implications with regard to the potential involvement of the cytochrome P450 metabolites of PUFAs in mediating the biological effects of TCDD and other agonists of AHR. PMID:24213002

  15. AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice.

    PubMed

    Crudele, Julie M; Finn, Jonathan D; Siner, Joshua I; Martin, Nicholas B; Niemeyer, Glenn P; Zhou, Shangzhen; Mingozzi, Federico; Lothrop, Clinton D; Arruda, Valder R

    2015-03-01

    Emerging successful clinical data on gene therapy using adeno-associated viral (AAV) vector for hemophilia B (HB) showed that the risk of cellular immune response to vector capsid is clearly dose dependent. To decrease the vector dose, we explored AAV-8 (1-3 × 10(12) vg/kg) encoding a hyperfunctional factor IX (FIX-Padua, arginine 338 to leucine) in FIX inhibitor-prone HB dogs. Two naïve HB dogs showed sustained expression of FIX-Padua with an 8- to 12-fold increased specific activity reaching 25% to 40% activity without antibody formation to FIX. A third dog with preexisting FIX inhibitors exhibited a transient anamnestic response (5 Bethesda units) at 2 weeks after vector delivery following by spontaneous eradication of the antibody to FIX by day 70. In this dog, sustained FIX expression reached ∼200% and 30% of activity and antigen levels, respectively. Immune tolerance was confirmed in all dogs after challenges with plasma-derived FIX concentrate. Shortening of the clotting times and lack of bleeding episodes support the phenotypic correction of the severe phenotype, with no clinical or laboratory evidence of risk of thrombosis. Provocative studies in mice showed that FIX-Padua exhibits similar immunogenicity and thrombogenicity compared with FIX wild type. Collectively, these data support the potential translation of gene-based strategies using FIX-Padua for HB. PMID:25568350

  16. AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice

    PubMed Central

    Crudele, Julie M.; Finn, Jonathan D.; Siner, Joshua I.; Martin, Nicholas B.; Niemeyer, Glenn P.; Zhou, Shangzhen; Mingozzi, Federico; Lothrop, Clinton D.

    2015-01-01

    Emerging successful clinical data on gene therapy using adeno-associated viral (AAV) vector for hemophilia B (HB) showed that the risk of cellular immune response to vector capsid is clearly dose dependent. To decrease the vector dose, we explored AAV-8 (1-3 × 1012 vg/kg) encoding a hyperfunctional factor IX (FIX-Padua, arginine 338 to leucine) in FIX inhibitor-prone HB dogs. Two naïve HB dogs showed sustained expression of FIX-Padua with an 8- to 12-fold increased specific activity reaching 25% to 40% activity without antibody formation to FIX. A third dog with preexisting FIX inhibitors exhibited a transient anamnestic response (5 Bethesda units) at 2 weeks after vector delivery following by spontaneous eradication of the antibody to FIX by day 70. In this dog, sustained FIX expression reached ∼200% and 30% of activity and antigen levels, respectively. Immune tolerance was confirmed in all dogs after challenges with plasma-derived FIX concentrate. Shortening of the clotting times and lack of bleeding episodes support the phenotypic correction of the severe phenotype, with no clinical or laboratory evidence of risk of thrombosis. Provocative studies in mice showed that FIX-Padua exhibits similar immunogenicity and thrombogenicity compared with FIX wild type. Collectively, these data support the potential translation of gene-based strategies using FIX-Padua for HB. PMID:25568350

  17. Coffee and liver health.

    PubMed

    Morisco, Filomena; Lembo, Vincenzo; Mazzone, Giovanna; Camera, Silvia; Caporaso, Nicola

    2014-01-01

    Coffee is one of the most widely used beverages in the world. It includes a wide array of components that can have potential implications for health. Several epidemiological studies associate coffee consumption with a reduced incidence of various chronic diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. Over the past 20 years, an increasing number of epidemiological and experimental studies have demonstrated the positive effects of coffee on chronic liver diseases. Coffee consumption has been inversely associated with the activity of liver enzymes in subjects at risk, including heavy drinkers. Coffee favours an improvement in hepatic steatosis and fibrosis, and a reduction in cirrhosis and the risk of hepatocellular carcinoma. The mechanisms of action through which it exerts its beneficial effects are not fully understood. Experimental studies show that coffee consumption reduces fat accumulation and collagen deposition in the liver and promotes antioxidant capacity through an increase in glutathione as well as modulation of the gene and protein expression of several inflammatory mediators. Animal and in vitro studies indicate that cafestol and kahweol, 2 diterpens, can operate by modulating multiple enzymes involved in the detoxification process of carcinogens causing hepatocellular carcinoma. It is unclear whether the benefits are significant enough to "treat" patients with chronic liver disease. While we await clarification, moderate daily unsweetened coffee use is a reasonable adjuvant to therapy for these patients. PMID:25291138

  18. Glycosylation and Liver Cancer

    PubMed Central

    Mehta, Anand; Herrera, Harmin; Block, Timothy

    2015-01-01

    Liver cancer is the 5th most common cancer, but the 2nd leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus (HBV) or hepatitis C virus infection (HCV). While chronic viral infection remains the main cause of liver disease and risk of HCC, rates of non –viral associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2–7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development. PMID:25727150

  19. Early Childhood Education.

    ERIC Educational Resources Information Center

    Elkind, David

    In five sections, this paper explores dimensions of early childhood education: schooling generally construed as nonparental instruction in knowledge, values, and skills. Section 1 looks at some of the factors which have contributed to the rapid growth of early childhood education in modern times. Section 2 briefly highlights the contributions of…

  20. Reframing Early Childhood Leadership

    ERIC Educational Resources Information Center

    Stamopoulos, Elizabeth

    2012-01-01

    Rapid changes in Australian education have intensified the role of early childhood leaders and led to unprecedented challenges. The Australian Curriculum (ACARA, 2011), mandated Australian "National Quality Framework" (NQF) for Early Childhood Education & Care (DEEWR, 2010b) and the "National Early Years Learning Framework" (EYLF) (DEEWR, 2009)…

  1. Childhood Roots of Schizophrenia

    ERIC Educational Resources Information Center

    Watt, Norman F.; Lubensky, Amy W.

    1976-01-01

    Earlier project reports compared childhood social behavior of nonmigratory schizophrenics and normal classmates by analyzing teachers' comments in school records. This article expands the sample to include migratory schizophrenics and analyzes childhood intellectual functioning. Behavioral differences indicated emotional immaturity and social…

  2. Childhood Obesity. ERIC Digest.

    ERIC Educational Resources Information Center

    Summerfield, Liane M.

    In this discussion of childhood obesity, the medical and psychological problems associated with the condition are noted. Childhood obesity most likely results from an interaction of nutritional, psychological, familial, and physiological factors. Three factors--the family, low-energy expenditure, and heredity--are briefly examined. Early…

  3. Early Childhood Centers

    ERIC Educational Resources Information Center

    Butin, Dan; Woolums, Jennifer

    2009-01-01

    Early childhood centers have become a common and necessary part of millions of Americans' lives. More women in the workforce, longer workweeks, and educational research supporting the importance of early education have all contributed to the rise of early childhood centers throughout the United States. Today, more than 30 percent of children under…

  4. Historian's Discovery of Childhood

    ERIC Educational Resources Information Center

    Frijhoff, Willem

    2012-01-01

    The "discovery of childhood" is a tricky notion because childhood is as much a fact of a biological and psychological nature as a cultural notion that through the centuries has been the object of changing perceptions, definitions, and images. Children barely speak in history; virtually everything we know about them is mediated by adults. Then how…

  5. Gene expression profiling indicates an increased capacity for proline, serine, and ATP synthesis and mitochondrial mass by the liver of steers grazing high vs. low endophyte-infected tall fescue.

    PubMed

    Liao, S F; Boling, J A; Matthews, J C

    2015-12-01

    Grazing -infected forages results in a variety of reduced animal performance parameters, collectively known as "fescue toxicosis." The initial, limited evaluations of hepatic mechanisms affected by fescue toxicosis have used transcriptomic expression profiling of experimental phenotypes developed by short-term feeding of concentrated ergot alkaloids or fescue seeds to rodents and steers. To assess the effects of fescue toxicosis in growing cattle using a commercially relevant phenotype, we induced fescue toxicosis in beef steers by summer-long grazing (89 to 105 d) of a single high toxic endophyte-infected tall fescue pasture (HE; 0.746 μg/g ergot alkaloids; 5.7 ha; = 10; BW = 267 ± 14.5 kg) vs. a low toxic endophyte tall fescue-mixed pasture (LE; 0.023 μg/g ergot alkaloids; 5.7 ha; = 9; BW = 266 ± 10.9 kg). High toxic endophyte tall fescue-mixed pasture steers had decreased BW (313 vs. 338 kg) and an increased potential for hepatic gluconeogenesis from AA-derived carbons. To gain a greater perspective into fescue toxicosis-induced hepatic metabolism and identify candidate regulatory mechanisms, the goal of the current research was to examine liver samples for changes in gene (mRNA) expression profiles using a Bovine Affymetrix microarray and selected reverse-transcription PCR and immunoblot analyses. The expression (false discovery rate < 10%; < 0.01) of 147 genes was increased (7 to 268%) and that of 227 was decreased (4 to 87%) in livers of HE vs. LE steers. The top (1) functional gene category was cell-mediated immune response (33 genes; ≤ 0.012), (2) canonical cell signaling pathway was primary immunodeficiency signaling (8 genes; ≤ 0.0003), and (3) canonical metabolic pathways were oxidative phosphorylation (5 genes; ≤ 0.016) and purine metabolism (8 genes; ≤ 0.029). High toxic endophyte tall fescue-mixed pasture steers had increased ( ≤ 0.022) expression of genes critical for increased (1) Pro () and Ser () synthesis, (2) shunting of AA carbons

  6. Childhood Cancer Statistics

    MedlinePlus

    ... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

  7. CHILDHOOD OBESITY AND ENVIRONMENTAL CHEMCALS

    PubMed Central

    La Merrill, Michele; Birnbaum, Linda S.

    2011-01-01

    Childhood and adolescent rates of obesity and overweight are continuing to increase in much of the world. Risk factors such as diet composition, excess caloric intake, decreased exercise, genetics, and the built environment are active areas of etiologic research. The obesogen hypothesis, which postulates that pre- and peri- natal chemical exposure can contribute to risk of childhood and adolescent obesity, remains relatively under-examined. This review surveys numerous classes of chemicals for which this hypothesis has been explored. We focus on human data where they exist and also discuss the findings of rodent and cell culture studies. Organochlorine chemicals as well as several classes of chemicals that are PPAR agonists are identified as possible risk factors for obesity. Recommendations for future epidemiologic and experimental research on the chemical origins of obesity are also given. PMID:21259261

  8. Childhood Maltreatment and Headache Disorders.

    PubMed

    Tietjen, Gretchen E

    2016-04-01

    Childhood maltreatment is substantiated in 12 % of children, but nearly 50 % adults recall having been neglected or abused as children. Maltreatment, especially emotional abuse, is associated with migraine. Dysregulation of the HPA axis, autonomic, immune, and metabolic systems appears to be a consequence of maltreatment, and is also reported in migraine. Areas of the brain structurally and functionally affected by childhood abuse and by migraine are also similar, and include the limbic system structures, which connect to pain regions in the brainstem. Putative mechanisms by which early life stress increases the likelihood of developing migraine include gene x environment interactions, in addition to epigenetic modifications via DNA methylation. These modifications are stable and may be transferred across generations, but they may also be reversed by some medications commonly used in migraine, including valproic acid and topiramate. PMID:26936357

  9. The dynamics of childhood poverty.

    PubMed

    Corcoran, M E; Chaudry, A

    1997-01-01

    Child poverty rates have remained high since the middle of the 1970s. While several trends, including declines in the number of children per family and increases in parental years of schooling, worked to reduce child poverty rates, several others, including show economic growth, widening economic inequality, and increases in the proportion of children living in mother-only families, had the opposite effect, pushing more children into poverty. Poverty is a common risk: One-third of all children will be poor for at least one year. For many, poverty lasts only a short while, but for a small percentage, poverty persists both throughout childhood and into the adult years. Poverty is not shared equally across different demographic groups. African-American children. Latino children, and children in mother-only families are disproportionately poor. Long-term poverty is even more concentrated than single-year poverty. In 1992, almost 90% of long-term poor children were African-American as compared to all poor children (single-year and long-term poor), of whom 60% were white. Both family structure and the labor market are implicated in long-term childhood poverty. Changes in employment of family members and changes in family composition are each strongly associated with transitions into and out of childhood poverty. Of these, changes in employment are the most important. PMID:9299836

  10. Introduction: Childhood implications of parental aging.

    PubMed

    Cedars, Marcelle I

    2015-06-01

    Men and women are increasingly delaying childbearing to the late 30s, the 40s and beyond. The implications of this societal change on childhood health and well-being have only recently been a focus of research. There are known increased perinatal risks associated with increasing maternal age, while paternal age seems to have a potentially greater negative impact on childhood health. Understanding the mechanisms underlying the aging of sperm and eggs, and how these changes impact offspring, is a critical next step as we work to help patients build healthy families. PMID:25936233

  11. Lot to give, got to live - the restless minds of the “Liver on Tour” project

    PubMed Central

    Macedo, Guilherme; Peixoto, Armando; Lopes, Susana

    2016-01-01

    The Liver on Tour was a special project devoted to increase the public awareness on Liver Health and Liver Diseases that the Portuguese Association for the Study of Liver Diseases launched throughout the country in 2010. PMID:27429718

  12. Metabolic syndrome and non-alcoholic fatty liver disease in liver surgery: The new scourges?

    PubMed Central

    Cauchy, François; Fuks, David; Zarzavadjian Le Bian, Alban; Belghiti, Jacques; Costi, Renato

    2014-01-01

    The aim of this topic highlight is to review relevant evidence regarding the influence of the metabolic syndrome (MS) and its associated liver manifestation, non-alcoholic fatty liver disease (NAFLD), on the development of liver cancer as well as their impact on the results of major liver surgery. MS and NAFLD, whose incidences are significantly increasing in Western countries, are leading to a changing profile of the patients undergoing liver surgery. A MEDLINE search was performed for relevant articles using the key words “metabolic syndrome”, “liver resection”, “liver transplantation”, “non alcoholic fatty liver disease”, “non-alcoholic steatohepatitis” and “liver cancer”. On one hand, the MS favors the development of primary liver malignancies (hepatocellular carcinoma and cholangiocarcinoma) either through NAFLD liver parenchymal alterations (steatosis, steatohepatitis, fibrosis) or in the absence of significant underlying liver parenchyma changes. Also, the existence of NAFLD may have a specific impact on colorectal liver metastases recurrence. On the other hand, the postoperative period following partial liver resection and liver transplantation is at increased risk of both postoperative complications and mortality. These deleterious effects seem to be related to the existence of liver specific complications but also higher cardio-vascular sensitivity in a setting of MS/NAFLD. Finally, the long-term prognosis after curative surgery joins that of patients operated on with other types of underlying liver diseases. An increased rate of patients with MS/NAFLD referred to hepatobiliary units has to be expected. The higher operative risk observed in this subset of patients will require specific improvements in their perioperative management. PMID:24868324

  13. Liver cancer mortality rate model in Thailand

    NASA Astrophysics Data System (ADS)

    Sriwattanapongse, Wattanavadee; Prasitwattanaseree, Sukon

    2013-09-01

    Liver Cancer has been a leading cause of death in Thailand. The purpose of this study was to model and forecast liver cancer mortality rate in Thailand using death certificate reports. A retrospective analysis of the liver cancer mortality rate was conducted. Numbering of 123,280 liver cancer causes of death cases were obtained from the national vital registration database for the 10-year period from 2000 to 2009, provided by the Ministry of Interior and coded as cause-of-death using ICD-10 by the Ministry of Public Health. Multivariate regression model was used for modeling and forecasting age-specific liver cancer mortality rates in Thailand. Liver cancer mortality increased with increasing age for each sex and was also higher in the North East provinces. The trends of liver cancer mortality remained stable in most age groups with increases during ten-year period (2000 to 2009) in the Northern and Southern. Liver cancer mortality was higher in males and increase with increasing age. There is need of liver cancer control measures to remain on a sustained and long-term basis for the high liver cancer burden rate of Thailand.

  14. Salvaging a Childhood Language

    PubMed Central

    Au, Terry Kit-fong; Oh, Janet S.; Knightly, Leah M.; Jun, Sun-Ah; Romo, Laura F.

    2008-01-01

    Childhood experience with a language seems to help adult learners speak it with a more native-like accent. Can analogous benefits be found beyond phonology? This study focused on adult learners of Spanish who had spoken Spanish as their native language before age 7 and only minimally, if at all, thereafter until they began to re-learn Spanish around age 14 years. They were compared with native speakers, childhood overhearers, and typical late-second-language (L2)-learners of Spanish. Both childhood speakers and overhearers spoke Spanish with a more native-like accent than typical late-L2-learners. On grammar measures, childhood speakers—although far from native-like—reliably outperformed childhood overhearers as well as typical late-L2-learners. These results suggest that while simply overhearing a language during childhood could help adult learners speak it with a more native-like phonology, speaking a language regularly during childhood could help re-learners use it with more native-like grammar as well as phonology. PMID:18496606

  15. Role of liver stem cells in hepatocarcinogenesis

    PubMed Central

    Xu, Lei-Bo; Liu, Chao

    2014-01-01

    Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the “cancer stem cell hypothesis”, which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells (liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future. PMID:25426254

  16. Liver Transplantation in Brazil.

    PubMed

    Bittencourt, Paulo Lisboa; Farias, Alberto Queiroz; Couto, Claudia Alves

    2016-09-01

    Over 1700 liver transplantations (LTs) are performed annually in Brazil. In absolute terms, the country performs more LT surgeries than anywhere else in Latin America and is third worldwide. However, due to its increasing population and inadequate donor organ supply, the country averages 5-10 LTs per million population, far lower than required. There is a marked heterogeneity in organ donation and LT activity throughout the country. Access to LT in the underprivileged North, Midwest, and Northeast regions of Brazil is scarce. Major challenges for the future of LT in Brazil will be to increase organ donation and access to LT. The reduction of those geographical disparities in donation, organ procurement, and LT due to political and financial constraints is of utmost importance. Liver Transplantation 22 1254-1258 2016 AASLD. PMID:27228568

  17. Should hepatitis B vaccination be introduced into childhood immunisation programmes in northern Europe?

    PubMed

    Zuckerman, Jane; van Hattum, Jan; Cafferkey, Mary; Gjørup, Ida; Hoel, Terje; Rummukainen, Maija-Liisa; Weiland, Ola

    2007-06-01

    Infection with hepatitis B causes between 500,000 and 1.2 million deaths per year worldwide, and is the leading cause of liver cancer. Over 12 years ago, WHO recommended that universal childhood hepatitis B vaccination be implemented globally. Despite this, Denmark, Finland, Iceland, Ireland, the Netherlands, Norway, Sweden, and the UK have yet to implement such a policy and instead currently adopt an "at-risk" strategy. Although all eight countries are classed as having low endemicity, factors such as increased travel and integration of immigrant communities are increasing the number of at-risk individuals in these countries. Considering the difficulty in identifying all at-risk individuals, and the lack of effectiveness of at-risk vaccination on reducing the overall incidence of hepatitis B, we recommend that these countries reassess their hepatitis B prevention strategies. Universal vaccination against hepatitis B is the only way to eliminate the major public-health impact of this disease. PMID:17521594

  18. Oral contraceptives and liver cancer.

    PubMed

    1997-11-01

    To date, nine case-control studies conducted in developed countries have identified an association between oral contraceptives (OCs) and liver cancer. The most recent population-based data from both developed and developing countries failed to confirm such an association, however. A study conducted by the World Health Organization in eight developing countries (Chile, China, Colombia, Israel, Kenya, Nigeria, Philippines, and Thailand), in which 122 women with liver cancer were matched with 802 controls, found no elevated risk for OC users compared with never-users (relative risk, 0.7; 95% confidence interval, 0.4-1.2). This study is particularly significant since it was conducted in countries where hepatitis B virus infection, an important risk factor for primary liver cancer, is widespread. In addition, population mortality data from the US, UK, Japan, and Sweden have failed to document increases in liver cancer cases coincident with increases in OC use. Given that population statistics can detect changes on the magnitude of a 40-50% decrease in the risk of ovarian and endometrial cancer related to OC use, they should be able to detect increases of two to 20 times the risk of liver cancer. The increased risk of liver cancer found in the case-control studies may reflect bias resulting from the small size of these studies. PMID:12348250

  19. Childhood cancer in Africa.

    PubMed

    Kruger, Mariana; Hendricks, Marc; Davidson, Alan; Stefan, Cristina D; van Eyssen, Ann L; Uys, Ronelle; van Zyl, Anel; Hesseling, Peter

    2014-04-01

    The majority of children with cancer live in low- and middle-income countries (LMICs) with little or no access to cancer treatment. The purpose of the paper is to describe the current status of childhood cancer treatment in Africa, as documented in publications, dedicated websites and information collected through surveys. Successful twinning programmes, like those in Malawi and Cameroon, as well as the collaborative clinical trial approach of the Franco-African Childhood Cancer Group (GFAOP), provide good models for childhood cancer treatment. The overview will hopefully influence health-care policies to facilitate access to cancer care for all children in Africa. PMID:24214130

  20. Orthotopic liver transplantation for giant liver haemangioma: A case report

    PubMed Central

    Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael

    2015-01-01

    In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient’s renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient’s lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network “Eurotransplant”. The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours. PMID:26722664

  1. Orthotopic liver transplantation for giant liver haemangioma: A case report.

    PubMed

    Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael

    2015-12-24

    In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours. PMID:26722664

  2. Childhood Maltreatment, PTSD, and Suicidal Behavior among African American Females.

    ERIC Educational Resources Information Center

    Thompson, Martie P.; Kaslow, Nadine J.; Lane, Danielle Bradshaw; Kingree, J. B.

    2000-01-01

    Investigates how childhood maltreatment and current post-traumatic stress disorder (PTSD) predict nonfatal suicide attempts among 335 African American women. PTSD in combination with any of the maltreatments of childhood increased the risk of suicide attempts. Suggests that interventions designed to reduce suicidal behavior should focus on women…

  3. Childhood as Social Investment, Rights and the Valuing of Education

    ERIC Educational Resources Information Center

    Kjorholt, Anne Trine

    2013-01-01

    This paper discusses the impact of and close interplay between global discourses on children, notions of (a good) childhood at the national and local levels and childhoods as these are lived and experienced in particular social contexts. Two increasingly powerful global images of children are explored: Children as individual subjects with rights…

  4. Trends in Demography of Childhood Poverty and Disability.

    ERIC Educational Resources Information Center

    Fujiura, Glenn T.; Yamaki, Kiyoshi

    2000-01-01

    This article presents childhood disability prevalence trends and their interaction with economic status. Estimates derived from National Health Interview Survey data (1983-96) indicate a significant increase in childhood disability rates. Analysis indicates a greater risk in single-parent households and a growing relationship between poverty and…

  5. Bilingualism and Multiculturalism Go to Early Childhood Programs.

    ERIC Educational Resources Information Center

    Fernandez, Roy Ceferino

    This presentation on the preparation of early childhood teachers addresses implication of multiculturalism and bilingual education in early childhood programs. The purpose of the presentation was threefold: (1) to increase understanding of bilingualism and multiculturalism; (2) to compare and contrast bilingualism and multiculturalism; and (3) to…

  6. Childhood Overweight: Parental Perceptions and Readiness for Change

    ERIC Educational Resources Information Center

    Howard, Kristen R.

    2007-01-01

    Although the national health crisis of childhood obesity is a well-documented problem, few if any clinical interventions have had success in curbing its growth. In fact, childhood obesity, along with its associated morbidities, continues to climb even in the face of increased awareness. Research shows that factors contributing to obesity are…

  7. Historical and Contemporary Evaluations of Early Childhood Programmes

    ERIC Educational Resources Information Center

    Saracho, Olivia N.

    2015-01-01

    Researchers continue to be interested in the evaluation of early childhood education programmes, their interventions, and the implementation of different types of evaluation. Their interest continues to increase and attract other researchers. In understanding the nature and appropriate use of evaluation in early childhood education and the basis…

  8. Key Concepts in Early Childhood Education and Care

    ERIC Educational Resources Information Center

    Nutbrown, Cathy

    2005-01-01

    This book aims to provide a series of starting points which will help readers to understand more about many key topics in early childhood education and care. In the rapidly changing field of early childhood education and care, it is becoming increasingly important for students and practitioners to have an awareness of the many topics that relate…

  9. Aesthetic Discourses in Early Childhood Settings: Dewey, Steiner, and Vygotsky

    ERIC Educational Resources Information Center

    Lim, Booyeun

    2004-01-01

    Early childhood, when young children are already capable of undergoing aesthetic experience, must be the starting point for aesthetic education. Despite increasing attention to the significant values of the arts in early childhood classrooms, no theoretical framework to support aesthetic education has been established. This article introduces the…

  10. Parental Perceptions of the Schools' Role in Addressing Childhood Obesity

    ERIC Educational Resources Information Center

    Murphy, Maureen; Polivka, Barbara

    2007-01-01

    As childhood obesity has increased, schools have struggled with their role in this epidemic. Parents with a school-age child in a suburban latchkey program were surveyed regarding their perceptions of childhood obesity, body mass index, and the school's role in prevention and treatment of obesity. More than 80% of participants identified…

  11. The Role of School Counselors in the Childhood Obesity Epidemic

    ERIC Educational Resources Information Center

    Larrier, Yvonne I.; Bakerson, Michelle A.; Linton, Jeremy M.; Walker, Lynne R.; Woolford, Susan J.

    2011-01-01

    Childhood obesity is a significant public health concern. Since 1960, the prevalence of childhood obesity in the United States increased dramatically from 5% to 16.9%. To date many interventions to address obesity in schools have focused on healthy changes to the content of vending machines, school lunches, and the addition of after school…

  12. Contemporary Trends and Developments in Early Childhood Education in China

    ERIC Educational Resources Information Center

    Zhu, Jiaxiong; Zhang, Jie

    2008-01-01

    Early childhood education in China has gone through a century-long development process and has made great progress in the past two decades. Contemporary early childhood education is becoming diverse in its forms and educational approaches, and is aligning itself with the increasingly open and diversified society. It is clear that early childhood…

  13. Internet Use during Childhood and the Ecological Techno-Subsystem

    ERIC Educational Resources Information Center

    Johnson, Genevieve Marie; Puplampu, Korbla P.

    2008-01-01

    Research findings suggest both positive and negative developmental consequences of Internet use during childhood (e.g., playing video games have been associated with enhanced visual skills as well as increased aggression). Several studies have concluded that environmental factors mediate the developmental impact of childhood online behaviour. From…

  14. Starting Strong II: Early Childhood Education and Care

    ERIC Educational Resources Information Center

    OECD Publishing (NJ3), 2006

    2006-01-01

    This review of early childhood education and care (ECEC) in twenty OECD countries describes the social, economic, conceptual and research factors that influence early childhood policy. These include increasing women's labour market participation; reconciling work and family responsibilities on a more equitable basis for women; confronting the…

  15. Infusing Early Childhood Mental Health into Early Intervention Services

    ERIC Educational Resources Information Center

    Grabert, John C.

    2009-01-01

    This article describes the process of enhancing early childhood mental health awareness and skills in non-mental health staff. The author describes a pilot training model, conducted the U.S. Army's Early Intervention Services, that involved: (a) increasing early childhood mental health knowledge through reflective readings, (b) enhancing…

  16. Nutritional Status and Liver Transplantation

    PubMed Central

    Merli, Manuela; Giusto, Michela; Giannelli, Valerio; Lucidi, Cristina; Riggio, Oliviero

    2012-01-01

    Chronic liver disease has a profound effect on nutritional status and undernourishment is almost universally present in patients with end-stage liver disease undergoing liver transplantation. In the last decades, due to epidemiological changes, a trend showing an increase in patients with end-stage liver disease and associated obesity has also been reported in developed countries. Nutrition abnormalities may influence the outcome after transplantation therefore, the importance to carefully assess the nutritional status in the work-up of patients candidates for liver transplantation is widely accepted. More attention has been given to malnourished patients as they represent the greater number. The subjective global nutritional assessment and anthropometric measurements are recognized in current guidelines to be adequate in identifying those patients at risk of malnutrition. Cirrhotic patients with a depletion in lean body mass and fat deposits have an increased surgical risk and malnutrition may impact on morbidity, mortality and costs in the post-transplantation setting. For this reason an adequate calorie and protein intake should always be ensured to malnourished cirrhotic patient either through the diet, or using oral nutritional supplements or by enteral or parenteral nutrition although studies supporting the efficacy of nutritional supplementation in improving the clinical outcomes after transplantation are still scarce. When liver function is restored, an amelioration in the nutritional status is expected. After liver transplantation in fact dietary intake rapidly normalizes and fat mass is progressively regained while the recovery of muscle mass can be slower. In some patients unregulated weight gain may lead to over-nutrition and may favor metabolic disorders (hypertension, hyperglycemia, hyperlipidemia). This condition, defined as ‘metabolic syndrome’, may play a negative role on the overall survival of liver transplant patients. In this report we

  17. Separate and Cumulative Effects of Adverse Childhood Experiences in Predicting Adult Health and Health Care Utilization

    ERIC Educational Resources Information Center

    Chartier, Mariette J.; Walker, John R.; Naimark, Barbara

    2010-01-01

    Objectives: Objectives of this population-based study were: (1) to examine the relative contribution of childhood abuse and other adverse childhood experiences to poor adult health and increased health care utilization and (2) to examine the cumulative effects of adverse childhood experiences on adult health and health care utilization. Methods:…

  18. Progression of Liver Disease

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  19. Liver Function Tests

    MedlinePlus

    ... herbal supplements you are taking. What are normal ranges for liver function tests? Normal ranges for liver function tests can vary by age, ... other factors. Laboratory test results usually provide normal ranges for each liver function test with your results. ...

  20. Liver Function Tests

    MedlinePlus

    ... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

  1. Pyogenic liver abscess

    MedlinePlus

    Liver abscess; Bacterial liver abscess ... There are many potential causes of liver abscesses, including: Abdominal infection, such as appendicitis , diverticulitis , or a perforated bowel Infection in the blood Infection of the bile draining tubes ...

  2. Diet and Your Liver

    MedlinePlus

    ... scarring of your liver (cirrhosis). For people with liver disease, even a small amount of alcohol can make ... time. Eating an unhealthy diet can lead to liver disease. For example, a person who eats a lot ...

  3. Adverse childhood experiences and health anxiety in adulthood.

    PubMed

    Reiser, Sarah J; McMillan, Katherine A; Wright, Kristi D; Asmundson, Gordon J G

    2014-03-01

    Childhood experiences are thought to predispose a person to the development of health anxiety later in life. However, there is a lack of research investigating the influence of specific adverse experiences (e.g., childhood abuse, household dysfunction) on this condition. The current study examined the cumulative influence of multiple types of childhood adversities on health anxiety in adulthood. Adults 18-59 years of age (N=264) completed a battery of measures to assess adverse childhood experiences, health anxiety, and associated constructs (i.e., negative affect and trait anxiety). Significant associations were observed between adverse childhood experiences, health anxiety, and associated constructs. Hierarchical multiple regression analysis indicted that adverse childhood experiences were predictive of health anxiety in adulthood; however, the unique contribution of these experience were no longer significant following the inclusion of the other variables of interest. Subsequently, mediation analyses indicated that both negative affect and trait anxiety independently mediated the relationship between adverse childhood experiences and health anxiety in adulthood. Increased exposure to adverse childhood experiences is associated with higher levels of health anxiety in adulthood; this relationship is mediated through negative affect and trait anxiety. Findings support the long-term negative impact of cumulative adverse childhood experiences and emphasize the importance of addressing negative affect and trait anxiety in efforts to prevent and treat health anxiety. PMID:24011493

  4. Retrograde reperfusion via vena cava lowers the risk of initial nonfunction but increases the risk of ischemic-type biliary lesions in liver transplantation--a randomized clinical trial.

    PubMed

    Heidenhain, Christoph; Heise, Michael; Jonas, Sven; Ben-Asseur, Manuela; Puhl, Gero; Mittler, Jens; Thelen, Armin; Schmidt, Sven; Langrehr, Jan; Neuhaus, Peter

    2006-09-01

    Initial nonfunction (INF) and biliary complications such as ischemic-type biliary lesion (ITBL) remain two major complications in clinical orthotopic liver transplantation (OLT). The influence of ischemia and reperfusion injury (I/R) as a significant risk factor for both complications is widely unquestioned. A new reperfusion technique that reduces I/R injury should lead to a reduction in both INF and ITBL. One hundred and thirty two OLT patients were included in this study and randomized into two groups. Group A underwent standard reperfusion with anterograde simultaneous arterial and portal reperfusion and group B received retrograde reperfusion via the vena cava before sequential anterograde reperfusion of portal vein and hepatic artery. Serum transaminase level as a surrogate parameter for I/R injury and serum bilirubin level as a parameter for graft function were significantly reduced during the first week after OLT in group B. INF rate was 7.7% in group A and 0% in group B (P = 0.058). ITBL incidence was 4.55% in group A versus 12.3% in group B (P = 0.053). Retrograde reperfusion seemed to be beneficial for hepatocytes, but was detrimental for the biliary epithelium. The unexplained increased incidence of ITBL after retrograde reperfusion will be focus of further investigation. PMID:16918535

  5. Childhood Vaccine Schedule

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... please turn Javascript on. When to Vaccinate What Vaccine Why Birth (or any age if not previously ...

  6. Reducing Childhood Obesity

    MedlinePlus

    ... Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... Ga. were the first three We Can! cities. Obesity Research: A New Approach The percentage of children ...

  7. Childhood Immunization Schedule

    MedlinePlus

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  8. Cardiovascular Conditions of Childhood

    MedlinePlus

    ... This childhood illness can result in long-term heart complications. Learn the symptoms, diagnosis and treatment for Kawasaki disease. Rheumatic Fever This inflammatory infection can occur after strep ...

  9. Childhood Cancer: Osteosarcoma

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Osteosarcoma KidsHealth > For Parents > Osteosarcoma Print A A A ... kids with osteosarcoma do recover. Risk for Childhood Osteosarcoma Osteosarcoma is most often seen in teenage boys. ...

  10. Reducing Childhood Obesity

    MedlinePlus

    ... To help counter the current epidemic of childhood obesity in the United States, five NIH institutes joined together in 2005 to start and promote an obesity-prevention program " We Can! "—"Ways to Enhance Children's ...

  11. Metabolic liver disease.

    PubMed

    McKiernan, Pat

    2012-06-01

    Diagnosis of metabolic liver disease requires a high level of diagnostic suspicion. Diet is usually the primary treatment for metabolic liver disease. Where indicated, liver transplantation provides lifelong functional correction of liver-based metabolic defects. Liver cell therapy warrants further study for the future treatment of metabolic liver disease. All families should receive genetic advice and pre-emptive management of future affected siblings. PMID:22521124

  12. Protective Effect of Salep on Liver

    PubMed Central

    Pourahmad, Morteza; Kargar Jahromi, Hossein; Kargar Jahromi, Zahra

    2015-01-01

    Background: Salep is used for various purposes in food industries and traditional medicine. Therefore, evaluation of its effect on the liver seems to be necessary. Objectives: The aim of this study was to assess salep effect on liver. Materials and Methods: In this experimental study, various concentrations of Salep were intraperitoneally administered to five groups of Wistar rats (control, placebo and 20, 40 and 80 mg/kg salep). After one month, liver enzymes and liver tissue were evaluated and compared between different groups. Results: Significant decreased level of liver enzymes, MDA (Malondialdehyde) and TOC (Total Oxidation Capacity) were found in various concentrations of salep administration. On the other hand, a significant increase was found in TAC (Total Antioxidant Capacity) level with various doses of salep. Conclusions: Elevated level of total protein and albumin and decreased level of liver enzyme by salep extract were found in this study. Therefore, this plant may be a useful medicine for patients with liver diseases. PMID:26034505

  13. Human immunodeficiency virus infection and the liver

    PubMed Central

    Crane, Megan; Iser, David; Lewin, Sharon R

    2012-01-01

    Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries. PMID:22489261

  14. Fibrosis in autoimmune and cholestatic liver disease.

    PubMed

    Penz-Österreicher, Melitta; Österreicher, Christoph H; Trauner, Michael

    2011-04-01

    Autoimmune and cholestatic liver disease account for a significant part of end-stage liver disease and are leading indications for liver transplantation. Especially cholestatic liver diseases (primary biliary cirrhosis and primary sclerosing cholangitis) appear to be different from other chronic liver diseases with regards to pathogenesis. Portal fibroblasts located in the connective tissue surrounding bile ducts appear to be different from hepatic stellate cells with regards to expression of marker proteins and response the profibrogenic and mitogenic stimuli. In addition there is increasing evidence for a cross talk between activated cholangiocytes and portal myofibroblasts. Several animal models have improved our understanding of the mechanisms underlying these chronic liver diseases. In the present review, we discuss the current concepts and ideas with regards to myofibroblastic cell populations, mechanisms of fibrosis, summarize characteristic histological findings and currently employed animal models of autoimmune and cholestatic liver disease. PMID:21497742

  15. Criminal consequences of childhood sexual victimization.

    PubMed

    Widom, C P; Ames, M A

    1994-04-01

    Using a prospective cohorts design, we assess the long-term criminal consequences of childhood sexual abuse through an examination of official criminal histories for a large sample of validated cases of childhood sexual abuse, compared to cases of physical abuse and neglect and a control group matched for age, race, sex, and approximate family socioeconomic status. Compared to other types of abuse and neglect, early childhood sexual abuse does not uniquely increase an individual's risk for later delinquent and adult criminal behavior. Childhood sexual abuse victims were at increased risk of arrest as a juvenile for being a runaway. As adults, child sexual abuse victims were at higher risk of arrest for sex crimes than controls, as were victims of physical abuse and neglect. Childhood sexual abuse victims were more likely to be arrested for prostitution as adults than other abuse and neglect victims and controls, regardless of gender. However, there was no support for a direct relationship among child sexual abuse, arrests for running away in adolescence, and adult arrests for prostitution. The findings also suggest an association for males between physical abuse and arrests for violent sex crimes (rape and/or sodomy). Caution is needed in interpreting these findings because of exclusive reliance on official record data and the possible impact of agency intervention. PMID:8187016

  16. Amebic liver abscess

    MedlinePlus

    Hepatic amebiasis; Extraintestinal amebiasis; Abscess - amebic liver ... Amebic liver abscess is caused by Entamoeba histolytica. This parasite causes amebiasis , an intestinal infection that is also called ...

  17. Ethical issues in split versus whole liver transplantation.

    PubMed

    Vulchev, Anntim; Roberts, John P; Stock, Peter G

    2004-11-01

    Technologic advances in split liver transplantation have resulted in an ethical dilemma. Although splitting a liver maximizes the number of patients receiving an organ transplant, it may increase the morbidity and mortality for the individual patient receiving the split liver. This essay explores the ethical issues involved in the allocation of split livers, and proposes general policy guidelines for the allocation of split versus whole liver transplants. PMID:15476469

  18. Do race, neglect, and childhood poverty predict physical health in adulthood? A multilevel prospective analysis.

    PubMed

    Nikulina, Valentina; Widom, Cathy Spatz

    2014-03-01

    Childhood neglect and poverty often co-occur and both have been linked to poor physical health outcomes. In addition, Blacks have higher rates of childhood poverty and tend to have worse health than Whites. This paper examines the unique and interacting effects of childhood neglect, race, and family and neighborhood poverty on adult physical health outcomes. This prospective cohort design study uses a sample (N=675) of court-substantiated cases of childhood neglect and matched controls followed into adulthood (M(age)=41). Health indicators (C-Reactive Protein [CRP], hypertension, and pulmonary functioning) were assessed through blood collection and measurements by a registered nurse. Data were analyzed using hierarchical linear models to control for clustering of participants in childhood neighborhoods. Main effects showed that growing up Black predicted CRP and hypertension elevations, despite controlling for neglect and childhood family and neighborhood poverty and their interactions. Multivariate results showed that race and childhood adversities interacted to predict adult health outcomes. Childhood family poverty predicted increased risk for hypertension for Blacks, not Whites. In contrast, among Whites, childhood neglect predicted elevated CRP. Childhood neighborhood poverty interacted with childhood family poverty to predict pulmonary functioning in adulthood. Gender differences in health indicators were also observed. The effects of childhood neglect, childhood poverty, and growing up Black in the United States are manifest in physical health outcomes assessed 30 years later. Implications are discussed. PMID:24189205

  19. Do race, neglect, and childhood poverty predict physical health in adulthood? A multilevel prospective analysis

    PubMed Central

    Nikulina, Valentina

    2015-01-01

    Childhood neglect and poverty often co-occur and both have been linked to poor physical health outcomes. In addition, Blacks have higher rates of childhood poverty and tend to have worse health than Whites. This paper examines the unique and interacting effects of childhood neglect, race, and family and neighborhood poverty on adult physical health outcomes. This prospective cohort design study uses a sample (N = 675) of court-substantiated cases of childhood neglect and matched controls followed into adulthood (Mage = 41). Health indicators (C-Reactive Protein [CRP], hypertension, and pulmonary functioning) were assessed through blood collection and measurements by a registered nurse. Data were analyzed using hierarchical linear models to control for clustering of participants in childhood neighborhoods. Main effects showed that growing up Black predicted CRP and hypertension elevations, despite controlling for neglect and childhood family and neighborhood poverty and their interactions. Multivariate results showed that race and childhood adversities interacted to predict adult health outcomes. Childhood family poverty predicted increased risk for hypertension for Blacks, not Whites. In contrast, among Whites, childhood neglect predicted elevated CRP. Childhood neighborhood poverty interacted with childhood family poverty to predict pulmonary functioning in adulthood. Gender differences in health indicators were also observed. The effects of childhood neglect, childhood poverty, and growing up Black in the United States are manifest in physical health outcomes assessed 30 years later. Implications are discussed. PMID:24189205

  20. Using old liver grafts for liver transplantation: where are the limits?

    PubMed

    Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

    2014-08-21

    The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts. PMID:25152573