Candidiasis of the liver and spleen in childhood

International Nuclear Information System (INIS)

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

1982-01-01

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 99 mTc-sulfur colloid and 67 Ga-citrate scintigraphy, gray-scale ultrasound, and body computed tomography (CT). Abnormalities were detected in every individual examined. 99 mTc-sulfur colloid scintigraphy revealed cold areas in the liver or spleen. With 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

Candidiasis of the liver and spleen in childhood

Energy Technology Data Exchange (ETDEWEB)

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.

Autoimmune diseases of the liver and biliary tract and overlap syndromes in childhood.

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Maggiore, G; Riva, S; Sciveres, M

2009-03-01

Autoimmune liver diseases in childhood includes Autoimmune Hepatitis (AIH) and Primary (Autoimmune) Sclerosing Cholangitis (P(A)SC). Both diseases are characterized by a chronic, immune-mediated liver inflammation involving mainly hepatocytes in AIH and bile ducts in PSC. Both diseases, if untreated, lead to liver cirrhosis. AIH could be classified, according to the autoantibodies pattern, into two subtypes: AIH type 1 presents at any age as a chronic liver disease with recurrent flares occasionally leading to liver cirrhosis and liver failure. Characterizing autoantibodies are anti-nuclear (ANA) and anti-smooth muscle (SMA), usually at high titer (>1:100). These autoantibodies are not specific and probably do not play a pathogenic role. AIH type 2 shows a peak of incidence in younger children, however with a fluctuating course. The onset is often as an acute liver failure. Anti-liver kidney microsome autoantibodies type 1 (LKM1) and/or anti-liver cytosol autoantibody (LC1) are typically found in AIH type 2 and these autoantibodies are accounted to have a potential pathogenic role. Diagnosis of AIH is supported by the histological finding of interface hepatitis with massive portal infiltration of mononuclear cells and plasmocytes. Inflammatory bile duct lesions are not unusual and may suggest features of ''overlap'' with P(A)SC. A diagnostic scoring system has been developed mainly for scientific purposes, but his diagnostic role in pediatric age is debated. Conventional treatment with steroids and azathioprine is the milestone of therapy and it is proved effective. Treatment withdrawal however should be attempted only after several years. Cyclosporin A is the alternative drug currently used for AIH and it is effective as steroids. P(A)SC exhibit a peak of incidence in the older child, typically in pre-pubertal age with a slight predominance of male gender. Small bile ducts are always concerned and the histological picture shows either acute cholangitis (bile duct

Increasing Early Childhood Preservice Teachers' Intercultural Sensitivity through the ABCs

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Monroe, Lisa; Ruan, Jiening

2018-01-01

While the early childhood student population has become increasingly diverse in the U.S., its teaching force remains primarily European American. The diverse student population demands that early childhood educators possess intercultural sensitivity in order to teach their culturally diverse learners effectively. This study examined the…

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

Science.gov (United States)

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

2015-01-01

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

Increased sinusoidal volume and solute extraction during retrograde liver perfusion

International Nuclear Information System (INIS)

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

1989-01-01

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

Candidiasis of the liver and spleen in childhood

Energy Technology Data Exchange (ETDEWEB)

Miller, J.H. (Childrens Hospital of Los Angeles, CA); 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.

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

Science.gov (United States)

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 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.

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

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

2015-01-01

The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. We evaluated the effect of food intake on LS in patients with different degrees of liver disease. We evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. Food intake increased PBF (51±10%, p1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

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

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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,…

Fibropolycystic liver disease in children

International Nuclear Information System (INIS)

Veigel, Myka Call; Prescott-Focht, Julia; Zinati, Reza; Rodriguez, Michael G.; Shao, Lei; Moore, Charlotte A.W.; Lowe, Lisa H.

2009-01-01

Fibropolycystic liver diseases are a group of associated congenital disorders that present most often in childhood. These disorders include congenital hepatic fibrosis, biliary hamartomas, autosomal dominant polycystic liver disease, choledochal cysts and Caroli disease. We present a discussion and illustrations of the embryology, genetics, anatomy, pathology, imaging approach and key imaging features that distinguish fibropolycystic liver disease in children. The pathogenesis of these disorders is believed to be abnormal development of the embryonic ductal plates, which ultimately form the liver and biliary systems. An understanding of the abnormal embryogenesis helps to explain the characteristic imaging features of these disorders. (orig.)

Childhood maltreatment is associated with increased body mass index and increased C-reactive protein levels in first-episode psychosis patients.

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Hepgul, N; Pariante, C M; Dipasquale, S; DiForti, M; Taylor, H; Marques, T R; Morgan, C; Dazzan, P; Murray, R M; Mondelli, V

2012-09-01

The high incidence of the metabolic syndrome in patients with psychosis is mainly attributed to antipsychotic treatment. However, it is also possible that psychological stress plays a role, inducing a chronic inflammatory process that may predispose to the development of metabolic abnormalities. We investigated the association between childhood maltreatment and inflammatory and metabolic biomarkers in subjects with first-episode psychosis and healthy controls. Body mass index (BMI), weight and waist circumference were measured in 95 first-episode psychosis patients and 97 healthy controls. Inflammatory and metabolic markers were measured in a subsample of 28 patients and 45 controls. In all the subjects we collected information on childhood maltreatment and recent stressors. Patients with childhood maltreatment had higher BMI [25.0 (S.E.=0.6) kg/m2] and C-reactive protein (CRP) levels [1.1 (S.E.=0.6) mg/dl] when compared with healthy controls [23.4 (S.E.=0.4) kg/m2, p=0.030 and 0.2 (S.E.=0.1) mg/dl, p=0.009, respectively]. In contrast, patients without childhood maltreatment were not significantly different from healthy controls for either BMI [24.7 (S.E.=0.6) kg/m2, p=0.07] or CRP levels [0.5 (S.E.=0.2) mg/dl, p=0.25]. After controlling for the effect of BMI, the difference in CRP levels across the three groups remained significant (F 2,58=3.6, p=0.035), suggesting that the increase in inflammation was not driven by an increase in adipose tissue. Childhood maltreatment is associated with higher BMI, and increased CRP levels, in patients with a first-episode psychosis. Further studies need to confirm the mechanisms underlying the putative causal relationship between childhood maltreatment and higher BMI, and whether this is indeed mediated by increased inflammation.

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

Science.gov (United States)

Pulgarón, Elizabeth R

2013-01-01

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

Increase in childhood asthma admissions in an urbanising population

African Journals Online (AJOL)

Objective. In South Africa, rapid urbanisation has increased the risk of childhood asthma. This report reviews the pattern of asthma admissions to the Paediatric Department of Ga-Rankuwa Hospital, South Africa, from 1986 to 1996. Design. Inpatient admission data were reviewed for 1986- 1996. A detailed analysis of the ...

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

Science.gov (United States)

Jereb, Sara; Trotovsek, Blaz; Skrbinc, Breda

2016-06-01

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. 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. 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.

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

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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…

Increased liver alkaline phosphatase and aminotransferase ...

African Journals Online (AJOL)

The effect of daily, oral administration of ethanolic extract of Khaya senegalensis stem bark (2mg/kg body weight) for 18days on the alkaline phosphatase, aspartate and alanine aminotransferase activities of rat liver and serum were investigated. Compared with the control, the activities of liver alkaline phosphatase (ALP), ...

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

Science.gov (United States)

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

2015-04-01

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

Childhood trauma increases the risk of post-traumatic stress disorder in response to first-episode psychosis.

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Bendall, Sarah; Alvarez-Jimenez, Mario; Hulbert, Carol A; McGorry, Patrick D; Jackson, Henry J

2012-01-01

To investigate the relationship between childhood trauma, post-traumatic stress symptoms due to the experience of childhood trauma, and post-traumatic stress symptoms due to the experience of psychosis. The current study assessed childhood trauma and post-traumatic stress disorder (PTSD) symptoms as a result of both childhood trauma and psychosis using the Impact of Events Scale - Revised, in a group of 36 people with first-episode psychosis. Reported rates of clinical level post-psychotic PTSD symptoms, childhood trauma and childhood trauma-related clinical level PTSD symptoms were 47% (95% CI 31-64%), 64% (95% CI 48-80%) and 39% (95% CI 23-55%), respectively. Reporting childhood trauma increased the risk of developing post-psychosis PTSD 27-fold (95% CI 2.96-253.80, p = 0.01). Having childhood trauma-related PTSD increased the risk of developing post-psychosis PTSD 20-fold (95% CI 3.38-123.25, p = 0.01). These risks were not explained by illness factors such as duration of untreated psychosis, age of onset or severity of psychotic symptoms. Those without post-psychotic PTSD symptoms at clinical levels were unlikely to report childhood trauma (6%; 95% CI 3-8%). These results suggest the cognitive, social and biological consequences of childhood trauma can prevent effective recovery from the trauma of acute first-episode psychosis resulting in post-psychotic PTSD. Treatment strategies for post-psychotic PTSD must address childhood trauma and related PTSD.

Increased carboxyhemoglobin level during liver resection with inflow occlusion.

Science.gov (United States)

Godai, Kohei; Hasegawa-Moriyama, Maiko; Kuniyoshi, Tamotsu; Matsunaga, Akira; Kanmura, Yuichi

2013-04-01

Controlling stress responses associated with ischemic changes due to bleeding and ischemia/reperfusion injury is essential for anesthetic management. Endogenous carboxyhemoglobin (COHb) is produced in the oxidative degradation of heme proteins by the stress-response enzyme heme oxygenase. Although the COHb level is elevated in critically ill patients, changes in endogenous COHb during anesthesia have not been well investigated. Therefore, we evaluated changes in endogenous COHb levels in patients undergoing liver resections with inflow occlusion. Levels of COHb were significantly increased after the Pringle maneuver. The inflow occlusion time in patients with increased COHb after the Pringle maneuver (∆COHb > 0.3 %) was significantly longer than in patients without increased COHb (∆COHb < 0.3 %) (P = 0.01). In addition, COHb changes were correlated with inflow occlusion time (P = 0.005, R(2) = 0.21). Neither total blood loss, transfusion volume of packed red blood cells, operation time, nor anesthetic time differed between patients with and without increased COHb. The results indicated that endogenous COHb levels were increased by inflow occlusion in patients undergoing liver resections, which suggests that changes in COHb may correlate with hepatic ischemia/reperfusion injury induced by inflow occlusion.

Indian Childhood Cirrhosis: Case Report and Pediatric Diagnostic Challenges

Directory of Open Access Journals (Sweden)

Jaivinder Yadav

2015-08-01

Full Text Available Introduction: Indian childhood cirrhosis is a chronic liver disease usually seen in paediatric age group and is unique to the Indian subcontinent. The definitive causative factor for the disease is not found till now but excess copper ingestion has been associated with it.Case presentation: An Indian origin one and half year old premorbidly normal male child presented with history of gradual distension of abdomen for 6 months and jaundice, generalized body swelling, high colour urine for 20 days. There was no history of any bleeding or feature suggestive of hepatic encephalopathy. On physical examination child was icteric, pale and had anasarca, massive hepatosplenomegaly and ascites. The child was evaluated for various causes of hepatic failure in pediatric age group including infective, metabolic and autoimmune etiologies. Unfortunately the child succumbed to the illness. The post-mortem liver biopsy and copper estimation cleared the air, revealing Indian childhood cirrhosis as the underlying etiology.Conclusion: Though Indian childhood cirrhosis is a rare entity and reported less frequently in literature, the treating pediatrician should keep this as a differential in case of pediatric hepatic failure. The liver biopsy and hepatic copper estimation are the gold standard diagnostic tests for diagnosing Indian Childhood cirrhosis.

Scannographic appearance of increased colloid uptake in the left liver lobe (Case presentation)

International Nuclear Information System (INIS)

Tadzher, Isak S.; Josifovska, Tatjana; Popgjorcheva, Daniela

1996-01-01

Incidentally increased uptake of Tc-99m sulfur colloid was found in scannographic images in the whole left liver lobe in all positions (PA, AP, DL, LL). The patient, a 60-year-old woman, was three years earlier cholocystecomized and had since occasional pain in the right upper abdominal quadrant due to biliary dyskinesia. Accessory spleen tissue was seen as well in the inferior lineal pole, probably presenting Shurer's phenomenon of 'lienis in liene' thus augmenting the serendipity of the scanographic findings. Imaging of the accessory spleen with heat denaturated spherocytes - Tc-99m confirmed the lienal structure of the tissue with preserved red pulp trabecular trapping mechanism in addition to phagocytic function of lineal Kupffer cells (in white pulp). Mebrofenin-Tc-99m (IDA-agent) showed in our patient normal distribution in both liver lobes contrary to focal nodular hyperplasia and adenoma of the liver where IDA-radio- pharmaceuticals have delayed clearance due to abnormal biliary canaliculi. In our patient uptake, distribution, excretion and liver washout of mebrofenin-Tc-99m was found to be normal. This is in favor of an exclusive, solitary increase of the number of Kupffer cells confined to the whole left lobe of the liver. Increased colloid uptake in the left liver lobe is dependent on a greater number of Kupffer cells pro volume than in the right lobe. (Author)

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

Science.gov (United States)

Villalobos-García, Daniel; Hernández-Muñoz, Rolando

2017-08-01

Hepatic ethanol oxidation increases according to its concentration and is raised to near-saturation levels of alcohol dehydrogenase (ADH); therefore, re-oxidation of NADH becomes rate limiting in ethanol metabolism by the liver. Adenosine is able to increase liver ethanol oxidation in both in vivo and in vitro conditions; the enhancement being related with the capacity of the nucleoside to accelerate the transport of cytoplasmic reducing equivalents to mitochondria, by modifying the subcellular distribution of the malate-aspartate shuttle components. In the present study, we explored the putative effects of adenosine and other purines on liver ethanol oxidation mediated by non-ADH pathways. Using the model of high precision-cut rat liver slices, a pronounced increase of ethanol oxidation was found in liver slices incubated with various intermediates of the purine degradation pathway, from adenosine to uric acid (175-230%, over controls). Of these, urate had the strongest (230%), whereas xanthine had the less pronounced effect (178% over controls). The enhancement was not abolished by 4-methylpyrazole, indicating that the effect was independent of alcohol dehydrogenase. Conversely, aminotriazole, a catalase inhibitor, completely abolished the effect, pointing out that this enhanced ethanol oxidation is mediated by catalase activity. It is concluded that the H 2 O 2 needed for catalase activity is derived from the oxidation of (hypo)xanthine by xanthine oxidase and the oxidation of urate by uricase. The present and previous data led us to propose that, depending on the metabolic conditions, adenosine might be able to stimulate the metabolism of ethanol through different pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased risk of antidepressant use in childhood cancer survivors

DEFF Research Database (Denmark)

Lund, Lasse Wegener; Winther, J.F.; Cederkvist, L

2015-01-01

to the National Prescription Drug Database, which worldwide is the oldest nationwide registry of prescription medication. Hazard ratios (HRs) for antidepressant use were estimated in a Cox proportional hazards model stratified on sex, with population comparisons as referents. RESULTS: Overall, childhood cancer......AIM: Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. METHODS: Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage....... Increased HRs of 30-50% were seen for survivors of cancers of all main groups (haematological malignancies, central nervous system (CNS) and solid tumors); the highest risk was among children treated with haematopoietic stem cell transplantation (HR, 1.9; 95% CI, 1.2-3.1). Our data suggested that the risk...

Childhood Obesity: A Review of Increased Risk for Physical and Psychological Co-morbidities

Science.gov (United States)

Pulgarón, Elizabeth R.

2013-01-01

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

A Public Health Issue that Increased Prevelance: Non-Acholic Fatty Liver Disease

Directory of Open Access Journals (Sweden)

Muammer Kara

2014-02-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD, is a liver disease, that occur in non alcohol users, with same histological features of alcoholic liver disease. The increased importance of NAFLD is depends on its close relation of current problems such as Type 2 Diabetes Mellitus and hyperlipidemia, and its high prevalence as %20-30, in Europe and Middle East. NAFLD has a wide spectrum from simple steatozis (SS, liver cell damage, non alcoholic steatohepatitis (NASH with inflammation to high stage fibrosis, and cirrhosis. Hepathocellular cancer and liver failure might develop in cirrhosis patients. Biopsy is gold standard for NAFLD diagnosis; differentiate from SS and NASH and defining NASH stages. Nutrition regulations and slow and continuous weight loss with regular exercises is still best treatment method [TAF Prev Med Bull 2014; 13(1.000: 65-76

Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease.

Science.gov (United States)

Pereira, Evelyn Nunes Goulart da Silva; Silvares, Raquel Rangel; Flores, Edgar Eduardo Ilaquita; Rodrigues, Karine Lino; Ramos, Isalira Peroba; da Silva, Igor José; Machado, Marcelo Pelajo; Miranda, Rosiane Aparecida; Pazos-Moura, Carmen Cabanelas; Gonçalves-de-Albuquerque, Cassiano F; Faria-Neto, Hugo Caire de Castro; Tibiriça, Eduardo; Daliry, Anissa

2017-01-01

This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle contrast imaging (LSCI), respectively. Oxidative stress and inflamatory parameters were analysed by TBARs, catalase enzyme activity, RT-PCR and ELISA. The participation of advanced glycation end-products (AGE) and its receptor RAGE was evaluated by the measurement of gene and protein expression of RAGE by RT-PCR and Western-blot, respectively and by liver and serum quantification of fluorescent AGEs. Wistar rats fed high-fat diet (HFD) showed increase in epididymal and abdominal fat content, systolic arterial blood pressure, fasting blood glucose levels, hepatic triglycerides and cholesterol, and impairment of glucose and insulin metabolisms. Liver histology confirmed the presence of steatosis and ultrasound analysis revealed increased liver size and parenchymal echogenicity in HFD-fed rats. HFD causes significant increases in leukocyte rolling and adhesion on hepatic microcirculation and decrease in liver microvascular blood flow. Liver tissue presented increase in oxidative stress and inflammtion. At 20 weeks, there was a significantly increase in AGE content in the liver and serum of HFD-fed rats and an increase in RAGE gene expression in the liver. The increase in liver AGE levels and microcirculatory disturbances could play a role in the pathogenesis of liver injury and are key components of NAFLD.

Childhood height increases the risk of prostate cancer mortality

DEFF Research Database (Denmark)

Aarestrup, J; Gamborg, M; Cook, M B

2015-01-01

cancers. Cox proportional hazards regressions were performed. RESULTS: 630 men had prostate cancer recorded as the underlying cause of death. Childhood height at age 13years was positively associated with prostate cancer-specific mortality (hazard ratio [HR]per z-score=1.2, 95% confidence interval [CI]: 1.1-1.3......). Associations were significant at all other childhood ages. Growth analyses showed that height at age 13years had a stronger association with prostate cancer-specific mortality than height at age 7, suggesting the association at age 7 is largely mediated through later childhood height. The tallest boys at age...... 13years had a significantly worse survival, but only when restricted to a diagnosis at years of age (HRz-score of 1=1.7, 95% CI: 1.3-2.4). These associations were significant at all other childhood ages. Childhood BMI was not associated with prostate cancer mortality or survival. CONCLUSION...

Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

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Haider Raza

2015-02-01

Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

Study Finds Small Increase in Cancer Risk after Childhood CT Scans

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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.

Parental stress and air pollution increase childhood asthma in China.

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Deng, Qihong; Deng, Linjing; Lu, Chan; Li, Yuguo; Norbäck, Dan

2018-08-01

Although air pollution and social stress may independently increase childhood asthma, little is known on their synergistic effect on asthma, particularly in China with high levels of stress and air pollution. To examine associations between exposure to a combination of parental stress and air pollution and asthma prevalence in children. We conducted a cohort study of 2406 preschool children in Changsha (2011-2012). A questionnaire was used to collect children's lifetime prevalence of asthma and their parental stress. Parental socioeconomic and psychosocial stresses were respectively defined in terms of housing size and difficulty concentrating. Children's exposure to ambient air pollutants was estimated using concentrations measured at monitoring stations. Associations between exposure to parental stress and air pollution and childhood asthma were estimated by multiple logistic regression models using odds ratio (OR) and 95% confidence interval (CI). Life time prevalence of asthma in preschool children (6.7%) was significantly associated with parental socioeconomic and psychosocial stresses with OR (95% CI) respectively 1.48 (1.02-2.16) and 1.64 (1.00-2.71). Asthma was also associated with exposure to air pollutants, with adjusted OR (95% CI) during prenatal and postnatal periods respectively 1.43 (1.10-1.86) and 1.35 (1.02-1.79) for SO 2 and 1.61 (1.19-2.18) and 1.76 (1.19-2.61) for NO 2 . The association with air pollution was significant only in children exposed to high parental stress, the association with parental stress was significant only in children exposed to high air pollution, and the association was the strongest in children exposed to a combination of parental stress and air pollution. Sensitivity analysis showed that the synergistic effects of parental stress and air pollution on childhood asthma were stronger in boys. Parental stress and air pollution were synergistically associated with increased childhood asthma, indicating a common biological

Glucagon infusion increases rate of purine synthesis de novo in rat liver

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Itakura, Mitsuo; Maeda, Noriaki; Tsuchiya, Masami; Yamashita, Kamejiro

1987-01-01

Based on the parallel increases of glucagon, the second peak of hepatic cAMP, and the rate of purine synthesis de novo in the prereplicative period in regenerating rate liver after a 70% hepatectomy, it was hypothesized that glucagon is responsible for the increased rate of purine synthesis de novo. To test this hypothesis, the effect of glucagon or dibutyryl cAMP infusion on the rate of purine synthesis de novo in rat liver was studied. Glucagon infusion but not insulin or glucose infusion increased the rate of purine synthesis de novo, which was assayed by [ 14 C]glycine or [ 14 C]formate incorporation, by 2.7- to 4.3-fold. Glucagon infusion increased cAMP concentrations by 4.9-fold and 5-phosphoribosyl-1-pyrophosphate concentrations by 1.5-fold in liver but did not change the specific activity of amidophosphoribosyltransferase or purine ribonucleotide concentrations. Dibutyryl cAMP infusion also increased the rate of purine synthesis de novo by 2.2- to 4.0-fold. Because glucagon infusion increased the rate of purine synthesis de novo in the presence of unchanged purine ribonucleotide concentrations, it is concluded that glucagon after infusion or in animals after a 70% hepatectomy is playing an anabolic role to increase the rate of purine synthesis de novo by increasing cAMP and 5-phosphoribosyl-1-pyrophosphate concentrations

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

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Xiaoqing Shao

2017-07-01

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

Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence.

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Harley, M

2010-10-01

Adolescent cannabis use has been shown in many studies to increase the risk of later psychosis. Childhood trauma is associated with both substance misuse and risk for psychosis. In this study our aim was to investigate whether there is a significant interaction between cannabis use and childhood trauma in increasing the risk for experiencing psychotic symptoms during adolescence.

The efficacy of aspartate aminotransferase-toplatelet ratio index for assessing hepatic fibrosis in childhood nonalcoholic steatohepatitis for medical practice

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Earl Kim

2013-01-01

Full Text Available Purpose: Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD, and it has become one of the most common causes of childhood chronic liver diseases which significant as a cause of liver related mortality and morbidity in children in the United States. The development of simpler and easier clinical indices for medical practice is needed to identify advanced hepatic fibrosis in childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST-to-platelet ratio index (APRI have been proposed as a simple and noninvasive predictor to evaluate hepatic fibrosis in several liver diseases. APRI could be a good alternative to detect pathologic change in childhood NAFLD. The purpose of this study is to validate the efficacy of APRI for assessing hepatic fibrosis in childhood NAFLD based on FibroScan. Methods: This study included 23 children with NAFLD who underwent FibroScan. Clinical, laboratory and radiological evaluation including APRI was performed. To confirm the result of this study, 6 patients received liver biopsy. Results: Factors associated with hepatic fibrosis (stiffness measurement &gt;5.9 kPa Fibroscan were triglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariate analysis, APRI were correlated with hepatic fibrosis (&gt;5.9 kPa. In receiver operating characteristics curve, APRI of meaningful fibrosis (cutoff value, 0.4669; area under the receiver operating characteristics, 0.875 presented sensitivity of 94%, specificity of 66%, positive predictive value of 94%, and negative predictive value of 64%. Conclusion: APRI might be a noninvasive, simple, and readily available method for medical practice to predict hepatic fibrosis of childhood NAFLD.

Combined dyslipidemia in childhood.

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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. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care.

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Vajro, Pietro; Ferrante, Lorenza; Lenta, Selvaggia; Mandato, Claudia; Persico, Marcello

2014-04-01

Advances in the management of children with chronic liver disease have enabled many to survive into adulthood with or without their native livers, so that the most common of these conditions are becoming increasingly common in adult hepatology practice. Because the aetiologies of chronic liver disease in children may vary significantly from those in adulthood, adults with paediatric-onset chronic liver disease may often present with clinical manifestations unfamiliar to their adulthood physician. Transition of medical care to adult practice requires that the adulthood medical staff (primary physicians and subspecialists) have a comprehensive knowledge of childhood liver disease and their implications, and of the differences in caring for these patients. Pending still unavailable Scientific Society guidelines, this article examines causes, presentation modes, evaluation, management, and complications of the main paediatric-onset chronic liver diseases, and discusses key issues to aid in planning a program of transition from paediatric to adult patients. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Childhood adversity accelerates intended reproductive timing in adolescent girls without increasing interest in infants.

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Stephanie Clutterbuck

Full Text Available 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.

Increased expression of PPARγ in high fat diet-induced liver steatosis in mice

International Nuclear Information System (INIS)

Inoue, Mitsutaka; Ohtake, Takaaki; Motomura, Wataru; Takahashi, Nobuhiko; Hosoki, Yayoi; Miyoshi, Shigeki; Suzuki, Yasuaki; Saito, Hiroyuki; Kohgo, Yutaka; Okumura, Toshikatsu

2005-01-01

The present study was performed to examine a hypothesis that peroxisome proliferator-activated receptor γ (PPARγ) is implicated in high fat diet-induced liver steatosis. Mice were fed with control or high fat diet containing approximately 10% or 80% cholesterol, respectively. Macroscopic and microscopic findings demonstrated that lipid accumulation in the liver was observed as early as 2 weeks after high fat diet and that high fat diet for 12 weeks developed a fatty liver phenotype, establishing a novel model of diet-induced liver steatosis. Gene profiling with microarray and real-time PCR studies demonstrated that among genes involved in lipid metabolism, adipogenesis-related genes, PPARγ and its targeted gene, CD36 mRNA expression was specifically up-regulated in the liver by high fat diet for 2 weeks. Immunohistochemical study revealed that PPARγ protein expression is increased in the nuclei of hepatocytes by high fat diet. It was also shown that protein expression of cAMP response element-binding protein (CREB), an upstream molecule of PPARγ, in the liver was drastically suppressed by high fat diet. All these results suggest for the first time that the CREB-PPARγ signaling pathway may be involved in the high fat diet-induced liver steatosis

Liver damage and senescence increases in patients developing hepatocellular carcinoma.

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Rey, Silvia; Quintavalle, Cristina; Burmeister, Katharina; Calabrese, Diego; Schlageter, Manuel; Quagliata, Luca; Cathomas, Gieri; Diebold, Joachim; Molinolo, Alfredo; Heim, Markus H; Terracciano, Luigi M; Matter, Matthias S

2017-08-01

Most patients with a hepatocellular carcinoma (HCC) have an underlying chronic liver inflammation, which causes a continuous damage leading to liver cirrhosis and eventually HCC. However, only a minority of cirrhotic patients develop HCC. To assess a possible differential impact of liver inflammation in patients developing HCC versus patients remaining tumor-free, we designed a longitudinal study and analysed liver tissue of the same patients (n = 33) at two points in time: once when no HCC was present and once several years later when an HCC was present. As a control group, we followed cirrhotic patients (n = 37) remaining tumor-free over a similar time frame. We analysed cell damage and senescence of hepatocytes by measuring γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, nuclear size, and telomere length. γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, in the first liver biopsy was similar in patients developing HCC later on and cirrhotic patients remaining tumor free. In contrast, γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, was significantly higher in the second non-tumoral liver biopsy of HCC patients than in the control patients. Consequently, the individual increase in γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, from the first biopsy to the second biopsy was significantly higher in patients developing HCC than in patients remaining tumor free. In addition, changes in nuclear size and telomere length revealed a more pronounced cell aging in patients developing HCC than in patients remaining tumor free. Hepatocytes from patients developing HCC go through more pronounced cell damage and senescence in contrast to cirrhotic patients remaining tumor free. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

ERAD defects and the HFE-H63D variant are associated with increased risk of liver damages in Alpha 1-Antitrypsin Deficiency

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Di Martino, Julie; Ruiz, Mathias; Garin, Roman; Restier, Lioara; Belmalih, Abdelouahed; Marchal, Christelle; Cullin, Christophe; Arveiler, Benoit; Fergelot, Patricia; Gitler, Aaron D.; Lachaux, Alain; Couthouis, Julien

2017-01-01

Background The most common and severe disease causing allele of Alpha 1-Antitrypsin Deficiency (1ATD) is Z-1AT. This protein aggregates in the endoplasmic reticulum, which is the main cause of liver disease in childhood. Based on recent evidences and on the frequency of liver disease occurrence in Z-1AT patients, it seems that liver disease progression is linked to still unknown genetic factors. Methods We used an innovative approach combining yeast genetic screens with next generation exome sequencing to identify and functionally characterize the genes involved in 1ATD associated liver disease. Results Using yeast genetic screens, we identified HRD1, an Endoplasmic Reticulum Associated Degradation (ERAD) associated protein, as an inducer of Z-mediated toxicity. Whole exome sequencing of 1ATD patients resulted in the identification of two variants associated with liver damages in Z-1AT homozygous cases: HFE H63D and HERPUD1 R50H. Functional characterization in Z-1AT model cell lines demonstrated that impairment of the ERAD machinery combined with the HFE H63D variant expression decreased both cell proliferation and cell viability, while Unfolded Protein Response (UPR)-mediated cell death was hyperstimulated. Conclusion This powerful experimental pipeline allowed us to identify and functionally validate two genes involved in Z-1AT-mediated severe liver toxicity. This pilot study moves forward our understanding on genetic modifiers involved in 1ATD and highlights the UPR pathway as a target for the treatment of liver diseases associated with 1ATD. Finally, these findings support a larger scale screening for HERPUD1 R50H and HFE H63D variants in the sub-group of 1ATD patients developing significant chronic hepatic injuries (hepatomegaly, chronic cholestasis, elevated liver enzymes) and at risk developing liver cirrhosis. PMID:28617828

Arsenite induced oxidative damage in mouse liver is associated with increased cytokeratin 18 expression

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Gonsebatt, M.E. [UNAM, Ciudad Universitaria, Dept. Medicina Genomica y Toxicologia Ambiental, Instituto de Investigaciones Biomedicas, Mexico (Mexico); Razo, L.M. del; Sanchez-Pena, L.C. [Seccion de Toxicologia, CINVESTAV, Mexico (Mexico); Cerbon, M.A. [Facultad de Quimica, UNAM, Departamento de Biologia, Mexico (Mexico); Zuniga, O.; Ramirez, P. [Facultad de Estudios Superiores Cuautitlan, UNAM, Laboratorio de Toxicologia Celular, Coordinacion General de Estudios de Posgrado e Investigacion, Cuautitlan Izcalli, Estado de Mexico (Mexico)

2007-09-15

Cytokeratins (CK) constitute a family of cytoskeletal intermediate filament proteins that are typically expressed in epithelial cells. An abnormal structure and function are effects that are clearly related to liver diseases as non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. We have previously observed that sodium arsenite (SA) induced the synthesis of CK18 protein and promotes a dose-related disruption of cytoplasmic CK18 filaments in a human hepatic cell line. Both abnormal gene expression and disturbance of structural organization are toxic effects that are likely to cause liver disease by interfering with normal hepatocyte function. To investigate if a disruption in the CK18 expression pattern is associated with arsenite liver damage, we investigated CK18 mRNA and protein levels in liver slices treated with low levels of SA. Organotypic cultures were incubated with 0.01, 1 and 10 {mu}M of SA in the absence and presence of N-acetyl cysteine (NAC). Cell viability and inorganic arsenic metabolism were determined. Increased expression of CK18 was observed after exposure to SA. The addition of NAC impeded the oxidative effects of SA exposure, decreasing the production of thiobarbituric acid-reactive substances and significantly diminishing the up regulation of CK18 mRNA and protein. Liver arsenic levels correlated with increased levels of mRNA. Mice treated with intragastric single doses of 2.5 and 5 mg/kg of SA showed an increased expression of CK18. Results suggest that CK18 expression may be a sensible early biomarker of oxidative stress and damage induced by arsenite in vitro and in vivo. Then, during SA exposure, altered CK expression may compromise liver function. (orig.)

Increasing risk of psychiatric morbidity after childhood onset type 1 diabetes

DEFF Research Database (Denmark)

Dybdal, Daniel; Tolstrup, Janne S; Sildorf, Stine M

2018-01-01

AIMS/HYPOTHESIS: The aim of this study was to investigate psychiatric morbidity following childhood onset of type 1 diabetes. METHODS: In a matched, population-based cohort study based on Danish national registers, we identified children and adolescents who had been diagnosed as an in- or outpati......AIMS/HYPOTHESIS: The aim of this study was to investigate psychiatric morbidity following childhood onset of type 1 diabetes. METHODS: In a matched, population-based cohort study based on Danish national registers, we identified children and adolescents who had been diagnosed as an in...... of psychiatric disorders as well as the effects of age at onset and duration of type 1 diabetes on the risk of subsequently developing psychiatric morbidities. RESULTS: An increased risk of being diagnosed with mood disorders and anxiety, dissociative, eating, stress-related and somatoform disorders was observed....... CONCLUSIONS/INTERPRETATION: In the years following type 1 diabetes onset, an increased risk of eating disorders, anxiety and mood disorders, substance misuse, and personality disorders was found. These findings highlight a clinical need to monitor the mental health of children and adolescents in the years...

Increased frontal functional networks in adult survivors of childhood brain tumors

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Hongbo Chen

2016-01-01

Full Text Available Childhood brain tumors and associated treatment have been shown to affect brain development and cognitive outcomes. Understanding the functional connectivity of brain many years after diagnosis and treatment may inform the development of interventions to improve the long-term outcomes of adult survivors of childhood brain tumors. This work investigated the frontal region functional connectivity of 16 adult survivors of childhood cerebellar tumors after an average of 14.9 years from diagnosis and 16 demographically-matched controls using resting state functional MRI (rs-fMRI. Independent component analysis (ICA was applied to identify the resting state activity from rs-fMRI data and to select the specific regions associated with executive functions, followed by the secondary analysis of the functional networks connecting these regions. It was found that survivors exhibited differences in the functional connectivity in executive control network (ECN, default mode network (DMN and salience network (SN compared to demographically-matched controls. More specifically, the number of functional connectivity observed in the survivors is higher than that in the controls, and with increased strength, or stronger correlation coefficient between paired seeds, in survivors compared to the controls. Observed hyperconnectivity in the selected frontal functional network thus is consistent with findings in patients with other neurological injuries and diseases.

[A rare differential diagnosis of a somatoform autonomous disorder of the gastro-intestinal tract: the hepatocellular liver carcinoma in childhood].

Science.gov (United States)

Voll, Renate

2008-07-01

A severely ill 11-year-old boy came to the child psychiatric outpatient department of the Fachkrankenhaus Neckargemünd with the diagnosis of a somatoform disorder. Main symptoms included nausea, vomiting, abdominal pain and diarrhoea. He wished to be examined in order to enter the Stephen-Hawking-School for physically handicapped children in the town of Neckargemünd. Manual examination revealed a palpable mass in the right upper quadrant of the abdomen, which was imaged as a tumour of the liver. During the subsequent operation, a 500 ml hepatocellular carcinoma was found. The symptoms of the hepatocellular carcinoma, which rarely occurs in childhood, can perfectly mimic those of a somatoform disorder of the gastro-intestinal tract.

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

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

2014-12-07

To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD). A case-control study was performed. Cases were 40 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (HFF ≥ 5%), and confirmed by liver biopsy with ≥ 5% of hepatocytes containing macrovesicular fat. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1) with the cases on age, gender, pubertal stage and as closely as possible on body mass index- standard deviation score. All participants underwent clinical examination, laboratory tests including zonulin, inflammatory and metabolic parameters, and MRI for measurement of HFF and visceral adipose tissue. Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD [median (interquartile range), 4.23 (3.18-5.89) vs 3.31 (2.05-4.63), P 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 zonulin and lobular inflammation (P = 0.23), ballooning (P = 0.10), fibrosis score (P = 0.18), or presence of nonalcoholic steatohepatitis (P = 0.17). Within the entire study population, zonulin levels were positively associated with gamma-glutamyl transferase, 2-h insulin, HFF, and negatively associated with whole-body insulin sensitivity index (WBISI), after adjustment for age, gender and pubertal status. When the associations were restricted to the group of NAFLD patients, 2-h insulin, hepatic fat, and WBISI retained statistical significance. Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of

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

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Byoung-Joon Song

2013-01-01

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

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

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Min Yang

2014-10-01

Full Text Available 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.

Liver transplantation from maastricht category 2 non-heart-beating donors: a source to increase the donor pool?

Science.gov (United States)

Otero, A; Gómez-Gutiérrez, M; Suárez, F; Arnal, F; Fernández-García, A; Aguirrezabalaga, J; García-Buitrón, J; Alvarez, J; Máñez, R

2004-04-01

The demand for liver transplantation has increasingly exceeded the supply of cadaver donor organs. Non-heart-beating donors (NHBDs) may be an alternative to increase the cadaver donor pool. The outcome of 20 liver transplants from Maastricht category 2 NHBD was compared with that of 40 liver transplants from heart-beating donors (HBDs). After unsuccessful cardiopulmonary resuscitation (CPR), cardiopulmonary support with simultaneous application of chest and abdominal compression (CPS; n = 6) or cardiopulmonary bypass (CPB; n = 14) was used to maintain the donors. At a minimum follow-up of 2 years, actuarial patient and graft survival rates with livers from Maastricht category 2 NHBD were 80% and 55%, respectively. Transplantation of organs from these donors was associated with a significantly higher incidence of primary nonfunction, biliary complications, and more severe initial liver dysfunction compared with organs from HBDs. The graft survival rates was 83% for livers from NHBDs preserved with CPS and 42% in those maintained with CPB.

CT diagnosis of neuroblastoma in childhood

International Nuclear Information System (INIS)

Li Xin; Zhang Liqun; Yang Zhiyong

1997-01-01

Purpose: To evaluate CT in the diagnosis of neuroblastoma in childhood. Materials and methods: Analysis of CT manifestations in 26 cases proved by operation and pathology, including neuroblastoma 21 cases, ganglioneuroblastoma 5 cases. Thorax 7 cases (27%), adrenal gland 16 cases (62%), abdomen-pelvis paravertebral sympathetic chain 3 cases (11%). Bolus injection of contrast medium was given in all cases. Results: Adrenal gland and posterior superior mediastinum were the most common sites for neuroblastoma. 73% of neuroblastoma had calcifications. Neuroblastoma was more commonly calcified than ganglioneuroblastoma. Metastases were also calcified. Degree of enhancement was associated with the type of neuroblastoma. Tumor extension into the spinal canal was seen in 2 cases. 43% neuroblastoma of adrenal directly invaded the kidney in 7 cases. Right lobe of liver was involved in 3 cases, metastases to liver in 1 case, enlargement of lymph nodes 19 cases. Approximately 68% of patients showed increase of urinary Vanilly-mandelic acid (VMA). Preoperative diagnostic accuracy was 92%. Conclusion: CT is recognized as a useful technique for the diagnosis of neuroblastoma. The site of predilection, calcification, lymph node metastases and VMA increase in urine or serum are important basis for diagnosis

Increase in left liver lobe function after preoperative right portal vein embolisation assessed with gadolinium-EOB-DTPA MRI.

Science.gov (United States)

Geisel, Dominik; Lüdemann, Lutz; Keuchel, Thomas; Malinowski, Maciej; Seehofer, Daniel; Stockmann, Martin; Hamm, Bernd; Gebauer, Bernhard; Denecke, Timm

2013-09-01

To prospectively evaluate the early development of regional liver function after right portal vein embolisation (PVE) with Gd-EOB-DTPA-enhanced MRI in patients scheduled for extended right hemihepatectomy. Ten patients who received a PVE before an extended hemihepatectomy were examined before and 14 days after PVE using Gd-EOB-DTPA-enhanced MRI of the liver. In these sequences representative region of interest measurements were performed in the embolised right (RLL) and the non-embolised left liver lobe (LLL). The volume as well as hepatic uptake index (HUI) was calculated independently for each lobe. Relative enhancement 14 days after PVE decreased in the RLL and increased significantly in the LLL (P DTPA-enhanced MRI, which could reflect the redirected portal venous blood flow and the rapid utilisation of a hepatic functional reserve. • Preoperative portal vein embolisation (PVE) is widely performed before right-sided hepatic resection. • PVE increases intravenous contrast medium uptake in the left lobe of liver. • The hepatic uptake index for the left liver lobe increases rapidly after PVE. • Left liver lobe function increase may be visualised by Gd-EOB-DTPA-enhanced MRI.

Modeling social norms increasingly influences costly sharing in middle childhood.

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House, Bailey R; Tomasello, Michael

2018-07-01

Prosocial and normative behavior emerges in early childhood, but substantial changes in prosocial behavior in middle childhood may be due to it becoming integrated with children's understanding of what is normative. Here we show that information about what is normative begins influencing children's costly sharing in middle childhood in a sample of 6- to 11-year-old German children. Information about what is normative was most influential when indicating what was "right" (i.e., "The right thing is to choose this"). It was less influential when indicating what was prescribed by a rule (i.e., "There is a rule that says to choose this") or when it indicated what the majority of people do (i.e., "Most people choose this"). These findings support the idea that middle childhood is when social norms begin to shape children's costly sharing and provide insight into the psychological foundations of the relationship between norms and prosocial behavior. Copyright © 2018 Elsevier Inc. All rights reserved.

Growth hormone increases and maturation decreases glutamine synthetase turnover rate in rat liver

International Nuclear Information System (INIS)

Lin, C.K.

1985-01-01

An investigation was made of the effect of hypophysectomy and growth hormone (GH) replacement regimen (1 mg/100 g twice daily for 30 days); and maturation (from 25 up to 90 days) on the liver and brain glutamine synthetase (GS) mass and turnover rates in rats. The first order decay rate of enzyme 14 C radioactivity was determined between 1 and 4 days to obtain the half-life (T/sub 1/2/) of GS. The hepatic GS mass was determined by immunoassay. GS turnover (GS/sub s/) was calculated from T/sub 1/2/ and the GS mass (i.e., K = 0.693/T/sub 1/2/; GS/sub s/ = K x GS mass). It was concluded that: (1) GS specific activity is not decreased by hypophysectomy or increased by GH. These results suggested that observed endocrine induced changes in GS are due to changes in GS mass. (2) The liver GS turnover rate is significantly reduced by hypophysectomy and increased by GH replacement. It was proposed that GH specifically enhances synthesis of GS in the liver. (3) Maturation (25, 40, 60, and 90 days) decreases GS turnover rate in both liver and brain of normal rats. This similar effect of maturation suggests that the observed age induced decline in GS turnover rate is not related to GH in all tissues

Small-for-Size Liver Transplantation Increases Pulmonary Injury in Rats: Prevention by NIM811

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Qinlong Liu

2012-01-01

Full Text Available Pulmonary complications after liver transplantation (LT often cause mortality. This study investigated whether small-for-size LT increases acute pulmonary injury and whether NIM811 which improves small-for-size liver graft survival attenuates LT-associated lung injury. Rat livers were reduced to 50% of original size, stored in UW-solution with and without NIM811 (5 μM for 6 h, and implanted into recipients of the same or about twice the donor weight, resulting in half-size (HSG and quarter-size grafts (QSG, respectively. Liver injury increased and regeneration was suppressed after QSG transplantation as expected. NIM811 blunted these alterations >75%. Pulmonary histological alterations were minimal at 5–18 h after LT. At 38 h, neutrophils and monocytes/macrophage infiltration, alveolar space exudation, alveolar septal thickening, oxidative/nitrosative protein adduct formation, and alveolar epithelial cell/capillary endothelial apoptosis became overt in the lungs of QSG recipients, but these alterations were mild in full-size and HSG recipients. Liver pretreatment with NIM811 markedly decreased pulmonary injury in QSG recipients. Hepatic TNFα and IL-1β mRNAs and pulmonary ICAM-1 expression were markedly higher after QSG transplantation, which were all decreased by NIM811. Together, dysfunctional small-for-size grafts produce toxic cytokines, leading to lung inflammation and injury. NIM811 decreased toxic cytokine formation, thus attenuating pulmonary injury after small-for-size LT.

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

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

2015-01-01

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

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

Science.gov (United States)

Kurz, Herbert; Riedler, Jose

2003-01-01

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

A paradoxical signal intensity increase in fatty livers using opposed-phase gradient echo imaging with fat-suppression pulses

International Nuclear Information System (INIS)

Mulkern, Robert V.; Voss, Stephan; Loeb Salsberg, Sandra; Krauel, Marta Ramon; Ludwig, David S.

2008-01-01

With the increase in obese and overweight children, nonalcoholic fatty liver disease has become more prevalent in the pediatric population. Appreciating subtleties of magnetic resonance (MR) signal intensity behavior from fatty livers under different imaging conditions thus becomes important to pediatric radiologists. We report an initially confusing signal behavior - increased signal from fatty livers when fat-suppression pulses are applied in an opposed-phase gradient echo imaging sequence - and seek to explain the physical mechanisms for this paradoxical signal intensity behavior. Abdominal MR imaging at 3 T with a 3-D volumetric interpolated breath-hold (VIBE) sequence in the opposed-phase condition (TR/TE 3.3/1.3 ms) was performed in five obese boys (14±2 years of age, body mass index >95th percentile for age and sex) with spectroscopically confirmed fatty livers. Two VIBE acquisitions were performed, one with and one without the use of chemical shift selective (CHESS) pulse fat suppression. The ratios of fat-suppressed over non-fat-suppressed signal intensities were assessed in regions-of-interest (ROIs) in five tissues: subcutaneous fat, liver, vertebral marrow, muscle and spleen. The boys had spectroscopically estimated hepatic fat levels between 17% and 48%. CHESS pulse fat suppression decreased subcutaneous fat signals dramatically, by more than 85% within regions of optimal fat suppression. Fatty liver signals, in contrast, were elevated by an average of 87% with CHESS pulse fat suppression. Vertebral marrow signal was also significantly elevated with CHESS pulse fat suppression, while spleen and muscle signals demonstrated only small signal increases on the order of 10%. We demonstrated that CHESS pulse fat suppression actually increases the signal intensity from fatty livers in opposed-phase gradient echo imaging conditions. The increase can be attributed to suppression of one partner of the opposed-phase pair that normally contributes to the

A paradoxical signal intensity increase in fatty livers using opposed-phase gradient echo imaging with fat-suppression pulses

Energy Technology Data Exchange (ETDEWEB)

Mulkern, Robert V.; Voss, Stephan [Harvard Medical School, Department of Radiology, Children' s Hospital Boston, Boston, MA (United States); Loeb Salsberg, Sandra; Krauel, Marta Ramon; Ludwig, David S. [Harvard Medical School, Department of Medicine, Children' s Hospital Boston, Boston, MA (United States)

2008-10-15

With the increase in obese and overweight children, nonalcoholic fatty liver disease has become more prevalent in the pediatric population. Appreciating subtleties of magnetic resonance (MR) signal intensity behavior from fatty livers under different imaging conditions thus becomes important to pediatric radiologists. We report an initially confusing signal behavior - increased signal from fatty livers when fat-suppression pulses are applied in an opposed-phase gradient echo imaging sequence - and seek to explain the physical mechanisms for this paradoxical signal intensity behavior. Abdominal MR imaging at 3 T with a 3-D volumetric interpolated breath-hold (VIBE) sequence in the opposed-phase condition (TR/TE 3.3/1.3 ms) was performed in five obese boys (14{+-}2 years of age, body mass index >95th percentile for age and sex) with spectroscopically confirmed fatty livers. Two VIBE acquisitions were performed, one with and one without the use of chemical shift selective (CHESS) pulse fat suppression. The ratios of fat-suppressed over non-fat-suppressed signal intensities were assessed in regions-of-interest (ROIs) in five tissues: subcutaneous fat, liver, vertebral marrow, muscle and spleen. The boys had spectroscopically estimated hepatic fat levels between 17% and 48%. CHESS pulse fat suppression decreased subcutaneous fat signals dramatically, by more than 85% within regions of optimal fat suppression. Fatty liver signals, in contrast, were elevated by an average of 87% with CHESS pulse fat suppression. Vertebral marrow signal was also significantly elevated with CHESS pulse fat suppression, while spleen and muscle signals demonstrated only small signal increases on the order of 10%. We demonstrated that CHESS pulse fat suppression actually increases the signal intensity from fatty livers in opposed-phase gradient echo imaging conditions. The increase can be attributed to suppression of one partner of the opposed-phase pair that normally contributes to the

The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children

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Anna Di Sessa

2017-07-01

Full Text Available The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood.

Liver scanning in diffuse liver disease

International Nuclear Information System (INIS)

Aiginger, P.; Atefie, K.; Scherak, O.; Wolf, A.; Hoefer, R.; Seyfried, H.

1975-01-01

The results of liver scans performed with sup(99m)Tc-sulphur colloid in 169 patients suffering from diffuse liver diseases and in 48 normal controls were evaluated. The patients with reactive hepatitis, acute hepatitis, chronic persistent hepatitis, fatty liver and fibrosis of the liver show only minimal deviations from the scintigraphic pattern. On the contrary, highly increased colloid uptake in the spleen is found in cases of chronic aggressive hepatitis, whilst the intrahepatic distribution of the colloid is approximately normal. In cases of liver cirrhosis, increased colloid uptake is found in the left lobe of the liver as well as in the spleen and in the bone marrow. Either normal findings or cirrhosis-like changes of the colloid distribution are observed in patients with alcoholic hepatitis. (orig.) [de

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

Science.gov (United States)

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

2012-01-01

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

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

Science.gov (United States)

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.

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

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Abidullah Khan

2016-01-01

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

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

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

2014-04-01

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

Portal Vein Embolization with Contralateral Application of Stem Cells Facilitates Increase of Future Liver Remnant Volume in Patients with Liver Metastases

International Nuclear Information System (INIS)

Ludvík, Jaroslav; Duras, Petr; Třeška, Vladislav; Matoušková, Táňa; Brůha, Jan; Fichtl, Jakub; Lysák, Daniel; Ferda, Jiří; Baxa, Jan

2017-01-01

ObjectivesThis study aimed to evaluate the progress of future liver remnant volume (FLRV) in patients with liver metastases after portal vein embolization (PVE) with the application of hematopoietic stem cells (HSCs) and compare it with a patients control group after PVE only.MethodsTwenty patients (group 1) underwent PVE with contralateral HSC application. Subsequently, CT volumetry with the determination of FLRV was performed at weekly intervals, in total three weeks. A sample of twenty patients (group 2) who underwent PVE without HSC application was used as a control group.ResultsThe mean of FLRV increased by 173.2 mL during three weeks after the PVE/HSC procedure, whereas by 98.9 mL after PVE only (p = 0.015). Furthermore, the mean daily growth of FLRV by 7.6 mL in group 1 was significantly higher in comparison with 4.1 mL in group 2 (p = 0.007).ConclusionsPVE with the application of HSC significantly facilitates growth of FLRV in comparison with PVE only. This method could be one of the new suitable approaches to increase the resectability of liver tumours.

Portal Vein Embolization with Contralateral Application of Stem Cells Facilitates Increase of Future Liver Remnant Volume in Patients with Liver Metastases

Energy Technology Data Exchange (ETDEWEB)

Ludvík, Jaroslav, E-mail: ludvikj@fnplzen.cz; Duras, Petr [Charles University, Department of Imaging Methods, University Hospital and Faculty of Medicine in Pilsen (Czech Republic); Třeška, Vladislav [Charles University, Department of Surgery, University Hospital and Faculty of Medicine in Pilsen (Czech Republic); Matoušková, Táňa [Charles University, Department of Imaging Methods, University Hospital and Faculty of Medicine in Pilsen (Czech Republic); Brůha, Jan; Fichtl, Jakub [Charles University, Department of Surgery, University Hospital and Faculty of Medicine in Pilsen (Czech Republic); Lysák, Daniel [Charles University, Department of Haemato-Oncology, University Hospital and Faculty of Medicine in Pilsen (Czech Republic); Ferda, Jiří; Baxa, Jan [Charles University, Department of Imaging Methods, University Hospital and Faculty of Medicine in Pilsen (Czech Republic)

2017-05-15

ObjectivesThis study aimed to evaluate the progress of future liver remnant volume (FLRV) in patients with liver metastases after portal vein embolization (PVE) with the application of hematopoietic stem cells (HSCs) and compare it with a patients control group after PVE only.MethodsTwenty patients (group 1) underwent PVE with contralateral HSC application. Subsequently, CT volumetry with the determination of FLRV was performed at weekly intervals, in total three weeks. A sample of twenty patients (group 2) who underwent PVE without HSC application was used as a control group.ResultsThe mean of FLRV increased by 173.2 mL during three weeks after the PVE/HSC procedure, whereas by 98.9 mL after PVE only (p = 0.015). Furthermore, the mean daily growth of FLRV by 7.6 mL in group 1 was significantly higher in comparison with 4.1 mL in group 2 (p = 0.007).ConclusionsPVE with the application of HSC significantly facilitates growth of FLRV in comparison with PVE only. This method could be one of the new suitable approaches to increase the resectability of liver tumours.

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

Science.gov (United States)

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

Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice.

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Du, Xianhong; Wu, Zhuanchang; Xu, Yong; Liu, Yuan; Liu, Wen; Wang, Tixiao; Li, Chunyang; Zhang, Cuijuan; Yi, Fan; Gao, Lifen; Liang, Xiaohong; Ma, Chunhong

2018-05-07

As an immune checkpoint, Tim-3 plays roles in the regulation of both adaptive and innate immune cells including macrophages and is greatly involved in chronic liver diseases. However, the precise roles of Tim-3 in nonalcoholic steatohepatitis (NASH) remain unstated. In the current study, we analyzed Tim-3 expression on different subpopulations of liver macrophages and further investigated the potential roles of Tim-3 on hepatic macrophages in methionine and choline-deficient diet (MCD)-induced NASH mice. The results of flow cytometry demonstrated the significantly increased expression of Tim-3 on all detected liver macrophage subsets in MCD mice, including F4/80 + CD11b + , F4/80 + CD68 + , and F4/80 + CD169 + macrophages. Remarkably, Tim-3 knockout (KO) significantly accelerated MCD-induced liver steatosis, displaying higher serum ALT, larger hepatic vacuolation, more liver lipid deposition, and more severe liver fibrosis. Moreover, compared with wild-type C57BL/6 mice, Tim-3 KO MCD mice demonstrated an enhanced expression of NOX2, NLRP3, and caspase-1 p20 together with increased generation of IL-1β and IL-18 in livers. In vitro studies demonstrated that Tim-3 negatively regulated the production of reactive oxygen species (ROS) and related downstream pro-inflammatory cytokine secretion of IL-1β and IL-18 in macrophages. Exogenous administration of N-Acetyl-L-cysteine (NAC), a small molecular inhibitor of ROS, remarkably suppressed caspase-1 p20 expression and IL-1β and IL-18 production in livers of Tim-3 KO mice, thus significantly reducing the severity of steatohepatitis induced by MCD. In conclusion, Tim-3 is a promising protector in MCD-induced steatohepatitis by controlling ROS and the associated pro-inflammatory cytokine production in macrophages.

Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function.

Science.gov (United States)

Kołodziejski, Paweł A; Pruszyńska-Oszmałek, Ewa; Strowski, Mathias Z; Nowak, Krzysztof W

2017-06-01

Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. Obestatin reduced body weight and decreased serum glucose, fructosamine, and β-hydroxybutyrate levels, as well as total and low-density lipoprotein fractions of cholesterol. In addition, obestatin increased high-density lipoproteins cholesterol levels and enhanced insulin sensitivity in mice with type 2 diabetes mellitus. Moreover, obestatin diminished liver mass, hepatic triglycerides and cholesterol contents, while glycogen content was higher in livers of healthy and mice with type 2 diabetes mellitus treated with obestatin. These changes were accompanied by reduction of increased alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transpeptidase in T2DM mice with type 2 diabetes mellitus. Obestatin increased adiponectin levels and reduced leptin concentration. Obestatin influenced the expression of genes involved in lipid and carbohydrate metabolism by increasing Fabp5 and decreasing G6pc, Pepck, Fgf21 mRNA in the liver. Obestatin increased both, AKT and AMPK phosphorylation, and sirtuin 1 (SIRT1) protein levels as well as mRNA expression in the liver. Obestatin improves metabolic abnormalities in type 2 diabetes mellitus, restores hepatic lipid contents and decreases hepatic enzymes. Therefore, obestatin could potentially have a therapeutic relevance in treating of insulin resistance and metabolic dysfunctions in type 2 diabetes mellitus.

Childhood liver diseases in Ga-Rankuwa Hospital, South Africa ...

African Journals Online (AJOL)

Rankuwa Hospital Histopathology Laboratory. Design: A retrospective study. Setting: Ga-Rankuwa Histopathology Laboratory. Subjects: Seventy two patients who underwent a liver biopsy during the study period. Methods: Laboratory records ...

Early Childhood Stress and Child Age Predict Longitudinal Increases in Obesogenic Eating Among Low-Income Children.

Science.gov (United States)

Miller, Alison L; Gearhardt, Ashley N; Retzloff, Lauren; Sturza, Julie; Kaciroti, Niko; Lumeng, Julie C

2018-01-31

To identify whether psychosocial stress exposure during early childhood predicts subsequent increased eating in the absence of hunger (EAH), emotional overeating, food responsiveness, and enjoyment of food. This was an observational longitudinal study. Among 207 low-income children (54.6% non-Hispanic white, 46.9% girls), early childhood stress exposure was measured by parent report and a stress exposure index calculated, with higher scores indicating more stress exposure. Eating behaviors were measured in early (mean, 4.3; standard deviation, 0.5 years) and middle (mean, 7.9; standard deviation, 0.7 years) childhood. Observed EAH was assessed by measuring kilocalories of palatable food the child consumed after a meal. Parents reported on child eating behaviors on the Child Eating Behavior Questionnaire. Child weight and height were measured and body mass index z score (BMIz) calculated. Multivariable linear regression, adjusting for child sex, race/ethnicity, and BMIz, was used to examine the association of stress exposure with rate of change per year in each child eating behavior. Early childhood stress exposure predicted yearly increases in EAH (β = 0.14; 95% confidence interval, 0.002, 0.27) and Emotional Overeating (β = 0.14; 95% confidence interval, 0.008, 0.27). Stress exposure was not associated with Food Responsiveness (trend for decreased Enjoyment of Food; β = -0.13; 95% confidence interval, 0.002, -0.26). All child obesogenic eating behaviors increased with age (P Early stress exposure predicted increases in child eating behaviors known to associate with overweight/obesity. Psychosocial stress may confer overweight/obesity risk through eating behavior pathways. Targeting eating behaviors may be an important prevention strategy for children exposed to stress. Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Childhood Obesity

OpenAIRE

Trandafir, Laura Mihaela; Ioniuc, Ileana; Miron, Ingrith

2017-01-01

Childhood obesity has important consequences for health and wellbeing both during childhood and also in later adult life. The rising prevalence of childhood obesity poses a major public health challenge in both developed and developing countries by increasing the burden of chronic non-communicable diseases. Despite the urgent need for effective preventative strategies, there remains disagreement over its definition due to a lack of evidence on the optimal cut-offs linking childhood BMI to dis...

Increased Expression of TGF-β1 in Correlation with Liver Fibrosis during Echinococcus granulosus Infection in Mice.

Science.gov (United States)

Liu, Yumei; Abudounnasier, Gulizhaer; Zhang, Taochun; Liu, Xuelei; Wang, Qian; Yan, Yi; Ding, Jianbing; Wen, Hao; Yimiti, Delixiati; Ma, Xiumin

2016-08-01

To investigate the potential role of transforming growth factor (TGF)-β1 in liver fibrosis during Echinococcus granulosus infection, 96 BALB/c mice were randomly divided into 2 groups, experimental group infected by intraperitoneal injection with a metacestode suspension and control group given sterile physiological saline. The liver and blood samples were collected at days 2, 8, 30, 90, 180, and 270 post infection (PI), and the expression of TGF-β1 mRNA and protein was determined by real-time quantitative RT-PCR and ELISA, respectively. We also evaluated the pathological changes in the liver during the infection using hematoxylin and eosin (H-E) and Masson staining of the liver sections. Pathological analysis of H-E stained infected liver sections revealed liver cell edema, bile duct proliferation, and structural damages of the liver as evidenced by not clearly visible lobular architecture of the infected liver, degeneration of liver cell vacuoles, and infiltration of lymphocytes at late stages of infection. The liver tissue sections from control mice remained normal. Masson staining showed worsening of liver fibrosis at the end stages of the infection. The levels of TGF-β1 did not show significant changes at the early stages of infection, but there were significant increases in the levels of TGF-β1 at the middle and late stages of infection (Pgranulosus infection may play a significant role in liver fibrosis associated with E. granulosus infection.

A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

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Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

2016-04-01

Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

Body mass index in school-aged children and the risk of routinely diagnosed non-alcoholic fatty liver disease in adulthood

DEFF Research Database (Denmark)

Zimmermann, Esther; Gamborg, Michael; Holst, Claus

2015-01-01

OBJECTIVE: The relation between childhood overweight and adult non-alcoholic fatty liver disease (NAFLD) is largely unknown. We investigated if weight and weight gain in childhood increases the risk of being diagnosed with NAFLD in routine clinical settings in adulthood. PARTICIPANTS: We studied.......23) per 1-unit gain in BMI z-score in men and women, respectively. Associations were similar when adjusted for BMI z-score at age 13 years, and were consistent across birth years. CONCLUSIONS: A BMI gain in school-aged children is associated with adult NAFLD. Intriguingly, BMI gain appears to have...

Liver fibrosis in bile duct-ligated rats correlates with increased hepatic IL-17 and TGF-β2 expression.

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Zepeda-Morales, Adelaida Sara M; Del Toro-Arreola, Susana; García-Benavides, Leonel; Bastidas-Ramírez, Blanca E; Fafutis-Morris, Mary; Pereira-Suárez, Ana L; Bueno-Topete, Miriam R

2016-01-01

BACKGROUND AND RATIONALE FOR THE STUDY: IL-17, TGF-β1/2 are cytokines involved in the development of kidney, pulmonary and liver fibrosis. However, their expression kinetics in the pathogenesis of cholestatic liver fibrosis have not yet been fully explored. The aim of the study was to analyze the expression of IL-17, RORγt, NKp46, TGF-β1, and TGF-β2 in the liver of rats with bile duct ligation (BDL). Hepatic IL-17A gene expression analyzed by qRT-PCR showed a dramatic increase of 350 and 10 fold, at 8 and 30 days post BDL, respectively. TGFβ1 and TGFβ2 gene expression significantly increased throughout the whole fibrotic process. At the protein level in liver homogenates, IL-17, TGF-β1, and RORγt significantly increased at 8 and 30 days after BDL. Interestingly, a significant increase in the protein levels of TGF-β2 and decrease of NKp46 was observed only 30 days after BDL. Unexpectedly, TGF-β2 exhibited stronger signals than TGF-β1 at the gene expression and protein levels. Histological analysis showed bile duct proliferation and collagen deposition. Our results suggest that pro-fibrogenic cytokines IL-17, TGF-β1 and, strikingly, TGF-β2 might be important players of liver damage in the pathogenesis of early and advanced experimental cholestatic fibrosis. Th17 cells might represent an important source of IL-17, while NK cell depletion may account for the perpetuation of liver damage in the BDL model.

Prevalence and Correlates of Suspected Nonalcoholic Fatty Liver Disease in Chinese Children

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Peige Song

2017-04-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD has become a serious public health problem worldwide; however, the availability of information on the prevalence of NAFLD in the general pediatric population is still limited. The primary aim of this study was to reveal the prevalence and correlates of suspected NAFLD in Chinese children at the national level. Data from the China Health and Nutrition Surveys (CHNS was used. Weight, height, waist circumference (WC, blood pressure (BP were measured for children aged 7–18 years. Blood samples were collected and analyzed. Children were classified as having suspected NAFLD if common causes of liver disease were excluded, and serum alanine aminotransferase (ALT values were above the established thresholds (>22.1 IU/L for girls and >25.8 IU/L for boys. A percentage of 9.03% (75 out of 831 of Chinese children was found to have suspected NAFLD. Overweight and obesity according to BMI percentiles, abdominal obesity, hyperuricemia (uric acid (UA > 327 μmol/L, and elevated total cholesterol (TC were all detected as the correlates of childhood suspected NAFLD when adjusting for other factors. Our study revealed the prevalence of suspected NAFLD in general Chinese children at the national level for the first time. Our findings indicate that suspected NAFLD in children is associated with increasing childhood morbidities, further studies are needed to better understand the prevalence of childhood NAFLD and its correlates, and large-scale programs should be launched to screen NAFLD in the pediatric population in China.

Enhanced depletion of glutathione and increased liver oxidative damage in aflatoxin-fed mice infected with Plasmodium berghei

DEFF Research Database (Denmark)

Ankrah, N A; Sittie, A; Addo, P G

1995-01-01

levels accompanied by a significant increase in serum cholinesterase and liver malonic dialdehyde levels in the mice fed aflatoxin compared with those in the control group. The results suggested that malaria parasites can enhance depletion of host glutathione and oxidative damage of the liver in mice fed...

Use of Antibiotics during pregnancy increases the risk of Asthma in early childhood

DEFF Research Database (Denmark)

Stensballe, Lone Graff; Simonsen, Jacob; Jensen, Signe Marie

2013-01-01

OBJECTIVES: To investigate the hypothesis that mother's use of antibiotics in pregnancy could influence asthma and eczema in early life. STUDY DESIGN: Subjects were included from the Copenhagen Prospective Study on Asthma in Childhood cohort of children born of mothers with asthma (N = 411). Severe...... verified eczema. All children were followed to age 5 years in a cohort study design. RESULTS: The Copenhagen Prospective Study on Asthma in Childhood data showed increased risk of asthma exacerbation (hazard ratio 1.98 [95% CI 1.08-3.63]) if mothers had used antibiotics during third trimester. The Danish...... asthma exacerbations and eczema were diagnosed by research unit physicians. Replication was sought in children from the Danish National Birth Cohort (N = 30 675). Asthma outcomes were hospitalization and use of inhaled corticosteroids. Eczema was defined by an algorithm developed from cases of clinically...

Prognosis, with evaluation of general biochemistry, of liver disease in lymphoedema cholestasis syndrome 1 (LCS1/Aagenaes syndrome).

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Drivdal, Monica; Trydal, Torleif; Hagve, Tor-Arne; Bergstad, Ingunn; Aagenaes, Oystein

2006-04-01

To investigate the prognosis of liver disease in Aagenaes syndrome (lymphoedema cholestasis syndrome 1 (LCS1)), which is an autosomal recessive inherited syndrome consisting of neonatal cholestasis with intermittent cholestatic episodes in childhood into adulthood and development of lymphoedema. Forty Norwegian patients are known to have this condition, 25 of whom are alive. A clinical description of the liver disease is supplied with a case-control study. In this paper we review the course of the liver disease in the Norwegian cohort of patients and present results from a case-control study in the patients above 10 years of age. The case-control study was performed on 15 patients without clinical cholestasis (itching and sometimes jaundice) at the time of the study. An evaluation of 11 patients above 15 years of age without chronic biochemical cholestasis (increased alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and/or serum bile acids) was also carried out. For each patient one randomly identified control person was included (15 in one study, 11 in the other). Cirrhosis with either transplantation or death in infancy or early childhood occurred in six patients; slowly developing cirrhosis occurred in three patients. Two patients may be in the process of developing cirrhosis. Significantly increased ALP and GGT levels were found in patients with normal liver biochemistry in the preceding years when compared with the case control group. Additionally, albumin was found to be lower in older patients. Compared with that for other types of hereditary neonatal cholestasis, patients with LCS1 have a relatively good prognosis. More than 50% can expect a normal life span.

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

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

2011-08-01

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

A High-Fat, High-Fructose Diet Induces Antioxidant Imbalance and Increases the Risk and Progression of Nonalcoholic Fatty Liver Disease in Mice

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Kanokwan Jarukamjorn

2016-01-01

Full Text Available 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.

Long-term intake of a high protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats

KAUST Repository

Diaz Rua, Ruben

2017-04-19

Intake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition. Moreover, changes in expression of genes involved in acid–base maintenance and oxidative stress indicate alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. Up-regulation of immune-related genes was also observed. In concordance with changes at gene expression level, we observed increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly increased hepatic mRNA and protein levels of HSP90, a marker of liver injury. Thus, we show for the first time that long-term consumption of an HP diet, resulting in a high acid load, results in a hepatic transcriptome signature reflecting increased TG deposition and increased signs of health risk (increased inflammation, alterations in the acid–base equilibrium and oxidative stress). Persistence of this altered metabolic status could have unhealthy consequences.

Long-term intake of a high protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats

KAUST Repository

Diaz Rua, Ruben; Keijer, Jaap; Palou, Andreu; van Schothorst, Evert M.; Oliver, Paula

2017-01-01

Intake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition. Moreover, changes in expression of genes involved in acid–base maintenance and oxidative stress indicate alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. Up-regulation of immune-related genes was also observed. In concordance with changes at gene expression level, we observed increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly increased hepatic mRNA and protein levels of HSP90, a marker of liver injury. Thus, we show for the first time that long-term consumption of an HP diet, resulting in a high acid load, results in a hepatic transcriptome signature reflecting increased TG deposition and increased signs of health risk (increased inflammation, alterations in the acid–base equilibrium and oxidative stress). Persistence of this altered metabolic status could have unhealthy consequences.

Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats.

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Díaz-Rúa, Rubén; Keijer, Jaap; Palou, Andreu; van Schothorst, Evert M; Oliver, Paula

2017-08-01

Intake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition. Moreover, changes in expression of genes involved in acid-base maintenance and oxidative stress indicate alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. Up-regulation of immune-related genes was also observed. In concordance with changes at gene expression level, we observed increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly increased hepatic mRNA and protein levels of HSP90, a marker of liver injury. Thus, we show for the first time that long-term consumption of an HP diet, resulting in a high acid load, results in a hepatic transcriptome signature reflecting increased TG deposition and increased signs of health risk (increased inflammation, alterations in the acid-base equilibrium and oxidative stress). Persistence of this altered metabolic status could have unhealthy consequences. Copyright © 2017 Elsevier Inc. All rights reserved.

Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

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Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

2018-01-01

An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

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

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Mikael Bjursell

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

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

Science.gov (United States)

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

2013-01-01

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

Childhood trauma and increased peripheral cytokines in young adults with major depressive: Population-based study.

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Pedrotti Moreira, Fernanda; Wiener, Carolina David; Jansen, Karen; Portela, Luis Valmor; Lara, Diogo R; Souza, Luciano Dias de Mattos; da Silva, Ricardo Azevedo; Oses, Jean Pierre

2018-06-15

The aim of this study was to evaluate the effect of childhood trauma in cytokine serum levels of individuals with MDD. This was a cross-sectional study population-based, with people aged 18 to 35. The Mini International Neuropsychiatric Interview (M.I.N.I) measured to current major depressive disorder (MDD). To evaluate traumatic experiences during childhood, the Childhood Trauma Questionnaire (CTQ) was applied. Serum TNF- α, IL-6 and IL-10 levels were measured by ELISA using a commercial kit. The total sample comprised 166 young adults, of these: 40.4% were subjects with MDD and childhood trauma and 59.6% were diagnosed with MDD without childhood trauma. In relation to serum interleukin levels, subjects with childhood trauma showed a significantly higher serum IL-6 (p = 0.013) and IL-10 levels (p = 0.022) to compare no childhood trauma. Subjects with childhood trauma was observed positive correlation between serum IL-6 and physical abuse (r = 0.232, p = 0.035) and emotional abuse (r = 0.460, p ≤ 0.001). Moreover, IL-10 were positive correlation with physical abuse (r = 0.258, p = 0.013). TNF- α was not associated with childhood trauma. Childhood maltreatment may result higher inflammation dysregulation in individuals with depression than individuals that no has childhood maltreatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Substance P increases liver fibrosis by differential changes in senescence of cholangiocytes and hepatic stellate cells.

Science.gov (United States)

Wan, Ying; Meng, Fanyin; Wu, Nan; Zhou, Tianhao; Venter, Julie; Francis, Heather; Kennedy, Lindsey; Glaser, Trenton; Bernuzzi, Francesca; Invernizzi, Pietro; Glaser, Shannon; Huang, Qiaobing; Alpini, Gianfranco

2017-08-01

Substance P (SP) is involved in the proliferation of cholangiocytes in bile duct-ligated (BDL) mice and human cholangiocarcinoma growth by interacting with the neurokinin-1 receptor (NK-1R). To identify whether SP regulates liver fibrosis during cholestasis, wild-type or NK-1R knockout (NK-1R -/- ) mice that received BDL or sham surgery and multidrug resistance protein 2 knockout (Mdr2 -/- ) mice treated with either an NK-1R antagonist (L-733,060) or saline were used. Additionally, wild-type mice were treated with SP or saline intraperitoneally. In vivo, there was increased expression of tachykinin precursor 1 (coding SP) and NK-1R in both BDL and Mdr2 -/- mice compared to wild-type mice. Expression of tachykinin precursor 1 and NK-1R was significantly higher in liver samples from primary sclerosing cholangitis patients compared to healthy controls. Knockout of NK-1R decreased BDL-induced liver fibrosis, and treatment with L-733,060 resulted in decreased liver fibrosis in Mdr2 -/- mice, which was shown by decreased sirius red staining, fibrosis gene and protein expression, and reduced transforming growth factor-β1 levels in serum and cholangiocyte supernatants. Furthermore, we observed that reduced liver fibrosis in NK-1R -/- mice with BDL surgery or Mdr2 -/- mice treated with L-733,060 was associated with enhanced cellular senescence of hepatic stellate cells and decreased senescence of cholangiocytes. In vitro, L-733,060 inhibited SP-induced expression of fibrotic genes in hepatic stellate cells and cholangiocytes; treatment with L-733,060 partially reversed the SP-induced decrease of senescence gene expression in cultured hepatic stellate cells and the SP-induced increase of senescence-related gene expression in cultured cholangiocytes. Collectively, our results demonstrate the regulatory effects of the SP/NK-1R axis on liver fibrosis through changes in cellular senescence during cholestatic liver injury. (Hepatology 2017;66:528-541). © 2017 by the American

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

International Nuclear Information System (INIS)

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.

2006-01-01

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

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

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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.

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

International Nuclear Information System (INIS)

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

1989-01-01

In male Wistar rats fed ad libitum (24% protein, 4.5 Kcal/gm), the [ 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

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

DEFF Research Database (Denmark)

Lissau, I; Sørensen, T I

1994-01-01

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 o...

Focal nodular hyperplasia of the liver: an unusual association with diabetes mellitus in a child and review of literature

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Trizzino Antonino

2010-05-01

Full Text Available Abstract Hepatic hemangioma, adenoma and focal nodular hyperplasia are the most frequent benign lesions of the liver, but they are all infrequent among pediatric population. The reports of focal nodular hyperplasia in children have recently increased in number, with many cases associated to drug intake, particularly to chemotherapy. We here describe, to our knowledge, the first case of focal nodular hyperplasia in association with diabetes mellitus in childhood.

Risk Factors Associated with Increased Morbidity in Living Liver Donation

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Helry L. Candido

2015-01-01

Full Text Available 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.

Lipopolysaccharide precipitates hepatic encephalopathy and increases blood-brain barrier permeability in mice with acute liver failure.

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Chastre, Anne; Bélanger, Mireille; Nguyen, Bich N; Butterworth, Roger F

2014-03-01

Acute liver failure (ALF) is frequently complicated by infection leading to precipitation of central nervous system complications such as hepatic encephalopathy (HE) and increased mortality. There is evidence to suggest that when infection occurs in ALF patients, the resulting pro-inflammatory mechanisms may be amplified that could, in turn, have a major impact on blood-brain barrier (BBB) function. The aim of this study was to investigate the role of endotoxemia on the progression of encephalopathy in relation to BBB permeability during ALF. Adult male C57-BL6 mice with ALF resulting from azoxymethane-induced toxic liver injury were administered trace amounts of the endotoxin component lipopolysaccharide (LPS). Effects on the magnitude of the systemic inflammatory response, liver pathology and BBB integrity were measured as a function of progression of HE, defined as time to loss of corneal reflex (coma). Lipopolysaccharide caused additional two- to seven-fold (P liver pathology and associated increases of circulating transaminases as well as increased hyperammonaemia consistent with a further loss of viable hepatocytes. LPS treatment of ALF mice led to a rapid precipitation of hepatic coma and the BBB became permeable to the 25-kDa protein immunoglobulin G (IgG). This extravasation of IgG was accompanied by ignificant up-regulation of matrix metalloproteinase-9 (MMP-9), an endopeptidase known to modulate opening of the BBB in a wide range of neurological disorders. These findings represent the first direct evidence of inflammation-related BBB permeability changes in ALF. © 2013 John Wiley & Sons A/S. Publishing by John Wiley & Sons Ltd.

Fatty Liver

International Nuclear Information System (INIS)

Filippone, A.; Digiovandomenico, V.; Digiovandomenico, E.; Genovesi, N.; Bonomo, L.

1991-01-01

The authors report their experience with the combined use of US and CT in the study of diffuse and subtotal fatty infiltration of the liver. An apparent disagreement was initially found between the two examinations in the study of fatty infiltration. Fifty-five patients were studied with US and CT of the upper abdomen, as suggested by clinics. US showed normal liver echogenicity in 30 patients and diffuse increased echogenicity (bright liver) in 25 cases. In 5 patients with bright liver, US demonstrated a solitary hypoechoic area, appearing as a 'skip area', in the quadrate lobe. In 2 patients with bright liver, the hypoechoic area was seen in the right lobe and exhibited no typical US features of 'Skip area'. Bright liver was quantified by measuring CT density of both liver and spleen. The relative attenuation values of spleen and liver were compared on plain and enhanced CT scans. In 5 cases with a hypoechoic area in the right lobe, CT findings were suggestive of hemangioma. A good correlation was found between broght liver and CT attenuation values, which decrease with increasing fat content of the liver. Moreover, CT attenuation values confirmed US findings in the study of typical 'skip area', by demonstrating normal density - which suggests that CT can characterize normal tissue in atypical 'skip area'

Assessment of pathologic increase in liver stiffness enables earlier diagnosis of CFLD: Results from a prospective longitudinal cohort study.

Directory of Open Access Journals (Sweden)

Victoria Klotter

Full Text Available About 30% of patients with Cystic Fibrosis (CF develop CF-associated liver disease (CFLD. Recent studies have shown that transient elastography (TE, as a method to quantify liver stiffness, allows non-invasive diagnosis of CFLD in adults and children with CF. Within this study we aimed to prospectively identify patients at risk for development of CFLD by longitudinal analysis of liver stiffness and fibrosis scores in a 5-year follow-up. 36 pediatric and 16 adult patients with initial liver stiffness below the cut-off value indicative of CFLD (6.3 kPa were examined by transient elastography for 4-5 years. TE, APRI-, and FIB-4-scores were assessed and compared by Kruskal-Wallis test and receiver operating characteristic (ROC-analysis. Frequencies were compared by Chi2-test. Among the 36 patients participating in this study, a subgroup of 9 patients developed liver stiffness >6.3 kPa after 4-5 years with an increase of ΔTE >0.38 kPa/a (the group with increasing liver stiffness was labelled TEinc. APRI- and FIB-4 scores confirmed the rationale for grouping. The frequency of CFLD assessed by conventional diagnosis was significantly higher in TEinc-group compared to the control group (TEnorm. None of the adult CF patients matched criteria for TEinc-group. For the first time it was shown that the non-invasive longitudinal assessment of TE allows identification of patients with progression of CFLD in a subgroup of juvenile but not in adult CF patients. Comparing TE to conventional fibrosis-scores underlined the strength of the continuous assessment of liver stiffness for the exact diagnosis of progressive CFLD. The newly described cut-off for pathologic increase of liver stiffness, ΔTEcutoff = 0.38kPa/a, might enable to detect developing CFLD using consequent follow up TE measurements before reaching the level of stiffness indicating established CFLD. Nevertheless, the limited size of the analyzed cohort should encourage a prospective, multi

Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose?

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Kalsi SS

2011-10-01

Full Text Available Sarbjeet S Kalsi1,2, David M Wood2–4, W Stephen Waring5, Paul I Dargan2–4 1Emergency Department, 2Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London; 3King's Health Partners, 4King's College London, London; 5York Teaching Hospital NHS Foundation Trust, York, UK Abstract: Paracetamol (acetaminophen, N-acetyl-p-aminophenol, 4-hydroxyacetanilide is the most common cause of acute liver failure in developed countries. There are a number of factors which potentially impact on the risk of an individual developing hepatotoxicity following an acute paracetamol overdose. These include the dose of paracetamol ingested, time to presentation, decreased liver glutathione, and induction of cytochrome P450 (CYP isoenzymes responsible for the metabolism of paracetamol to its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI. In this paper, we review the currently published literature to determine whether induction of relevant CYP isoenzymes is a risk factor for hepatotoxicity in patients with acute paracetamol overdose. Animal and human in vitro studies have shown that the CYP isoenzyme responsible for the majority of human biotransformation of paracetamol to NAPQI is CYP2E1 at both therapeutic and toxic doses of paracetamol. Current UK treatment guidelines suggest that patients who use a number of drugs therapeutically should be treated as “high-risk” after paracetamol overdose. However, based on our review of the available literature, it appears that the only drugs for which there is evidence of the potential for an increased risk of hepatotoxicity associated with paracetamol overdose are phenobarbital, primidone, isoniazid, and perhaps St John's wort. There is no evidence that other drugs often quoted as increasing risk, such as carbamazepine, phenytoin, primidone, rifampicin, rifabutin, efavirenz, or nevirapine, should be considered risk factors for hepatotoxicity in patients presenting with acute paracetamol overdose. Keywords

Perioperative liver and spleen elastography in patients without chronic liver disease.

Science.gov (United States)

Eriksson, Sam; Borsiin, Hanna; Öberg, Carl-Fredrik; Brange, Hannes; Mijovic, Zoran; Sturesson, Christian

2018-02-27

To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors. Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s ( P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more ( P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy ( n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin ( R 2 = 0.154, Pearson's r = 0.392, P = 0.032) and international normalized ratio ( R 2 = 0.285, Pearson's r = 0.534, P = 0.003). Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease.

Twenty years of childhood coeliac disease in The Netherlands: A rapidly increasing incidence

NARCIS (Netherlands)

George, E.K.; Mearin, M.L.; Franken, H.C.M.; Houwen, R.H.J.; Hirasing, R.A.; Vandenbroucke, J.P.

1997-01-01

Background - The incidence of coeliac disease varies internationally. Aims - To assess the incidence of childhood coeliac disease in The Netherlands and to study the clinical features and the presence of associated disorders. Subjects - Identified cases of childhood coeliac disease in The

The increase of metallothionein content in rat liver induced by x-ray irradiation and its physiological function

International Nuclear Information System (INIS)

Shiraishi, Noriyuki; Miyahara, Masanobu; Utsumi, Kozo; Aono, Kaname; Inoue, Bunji.

1982-01-01

Whether or not stress promotes peroxidase reaction of lipids in vivo influences the biosynthesis of metallothionein (MT) was studied. After X-ray irradiation rats were exposed to oxygen, and the liver supernatant was examined. The Zn distribution in the liver supernatant fraction of 10,000 in molecular weight, which was attributed to MT in origin, was small in the control group, but was great in the stress group. The amount of Cd found to the 10,000 fraction (Zn in MT is relatively easily replaced by Cd) was extremely smaller in the control group than in the stress group. These data indicate that the amount of Zn is small, with no appreciable presence of MT, in the 10,000 fraction of the control group. The X-ray irradiated group showed a marked increase of Zn 5 and 7 days later, indicating a definite increase of MT, and the group exposed to O 2 showed similar phenomena, suggesting induction of MT synthesis in the rat liver. (Chiba, N.)

Liver protein expression in dairy cows with high liver triglycerides in early lactation

DEFF Research Database (Denmark)

Sejersen, Henrik; Sørensen, Martin Tang; Larsen, Torben

2012-01-01

Fatty liver is a frequent subclinical health disorder in dairy cows that may lead to disorders related to the liver function. However, the effect of triglyceride (TG) accumulation on liver metabolic pathways is still unclear. The objective was, therefore, to characterize quantitative differences...... in the liver proteome between early lactation dairy cows with a low or high liver TG content. The liver proteome analysis indicated that a high liver TG content in early lactation dairy cows is associated with increased oxidation of saturated fatty acids, oxidative stress, and urea synthesis...... and decreasedoxidation of unsaturated fatty acids. Furthermore, liver gluconeogenesis is apparently not impaired by an increased liver TG content. Based on correlations between liver proteins and plasma components, we suggest that future studies investigate the sensitivity and specificity of plasma aspartate...

Self-reported history of childhood smoking is associated with an increased risk for peripheral arterial disease independent of lifetime smoking burden.

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James R Priest

Full Text Available Atherosclerotic disorders are well known to be associated with obesity, lipid profile, smoking, hypertension and other medical comorbidities, and large cohort studies have explored the childhood correlates to these adult risk factors. However, there has been little investigation into the childhood risk factors for peripheral arterial disease (PAD. We endeavored to better understand the role of smoking in childhood in the risk for PAD in a well described cohort of 1,537 adults at high risk for cardiovascular disease. In a multivariate regression model, we observed an increased risk of PAD among those who reported a history of smoking during childhood (OR = 2.86; 95% CI, 1.99-4.11; P<0.001, which remained statistically significant after controlling for lifetime smoking burden (OR = 1.55; 95% CI, 1.00-2.41; P = 0.049. Our novel observation of disproportionate risk of PAD conferred by a history of childhood smoking may reflect an unrecognized biological mechanism such as a unique susceptibility to vascular injury or an unaccounted for covariate such as secondhand smoke exposure in childhood. This observation suggests further investigation is required into the pathophysiology of smoking in the developing vasculature and the need for detailed clinical data about patterns of childhood smoking and smoke exposure.

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

Science.gov (United States)

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.

Aging and a long-term diabetes mellitus increase expression of 1 α-hydroxylase and vitamin D receptors in the rat liver.

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Vuica, Ana; Ferhatović Hamzić, Lejla; Vukojević, Katarina; Jerić, Milka; Puljak, Livia; Grković, Ivica; Filipović, Natalija

2015-12-01

Diabetes mellitus (DM) is a metabolic disorder associated with serious liver complications. As a metabolic chronic disease, DM is very common in the elderly. Recent studies suggest ameliorating effects of vitamin D on metabolic and oxidative stress in the liver tissue in an experimental model of DM. The aim of this study was to investigate the expression of vitamin D receptors (VDRs) and 1α-hydroxylase, the key enzyme for the production of active vitamin D form (calcitriol) in the liver during long-term diabetes mellitus type 1 (DM1) in aging rats. We performed immunohistochemical analysis of liver expression of 1α-hydroxylase and VDRs during aging in long-term streptozotocin-induced DM1. 1α-Hydroxylase was identified in the monocyte/macrophage system of the liver. In addition to the nuclear expression, we also observed the expression of VDR in membranes of lipid droplets within hepatocytes. Aging and long-term DM1 resulted in significant increases in the number of 1α-hydroxylase immunoreactive cells, as well as the percentage of strongly positive VDR hepatocytes. In conclusion, the liver has the capacity for active vitamin D synthesis in its monocyte/macrophage system that is substantially increased in aging and long-term diabetes mellitus. These conditions are also characterized by significant increases in vitamin D receptor expression in hepatocytes. The present study suggests that VDR signaling system could be a potential target in prevention of liver complications caused by diabetes and aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Stages of Childhood Hodgkin Lymphoma

Science.gov (United States)

... Version Key Points Childhood Hodgkin lymphoma is a disease in which malignant (cancer) cells form in the lymph system. There are two types of childhood Hodgkin lymphoma. Epstein-Barr virus infection increases the risk of childhood Hodgkin ...

Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets.

Science.gov (United States)

Rodrigues, Angélica Heringer; Moreira, Carolina Campos Lima; Neves, Maria José; Botion, Leida Maria; Chaves, Valéria Ernestânia

2018-06-01

Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets. Copyright © 2018. Published by Elsevier Inc.

Childhood adversity increases the risk of onward transmission from perinatal HIV-infected adolescents and youth in South Africa.

Science.gov (United States)

Kidman, Rachel; Nachman, Sharon; Dietrich, Janan; Liberty, Afaaf; Violari, Avy

2018-05-01

Repeated exposure to childhood adversity (abuse, neglect and other traumas experienced before age 18) can have lifelong impacts on health. For HIV-infected adolescents and youth, such impacts may include onward transmission of HIV. To evaluate this possibility, the current study measured the burden of childhood adversity and its influence on risky health behaviors among perinatally-infected adolescents and youth. We surveyed 250 perinatally-infected adolescents and youth (13-24 years) receiving care in Soweto, South Africa. Both male and female participants reported on childhood adversity (using the ACE-IQ), sexual behavior, and psychosocial state. Viral load was also abstracted from their charts. We used logistic regressions to test the association between cumulative adversity and behavioral outcomes. Half the sample reported eight or more adversities. Overall, 72% experienced emotional abuse, 59% experienced physical abuse, 34% experienced sexual abuse, 82% witnessed domestic violence, and 91% saw someone being attacked in their community. A clear gradient emerged between cumulative adversities and behavioral risk. Having experienced one additional childhood adversity raised the odds of risky sexual behavior by almost 30% (OR 1.27, 95% CI 1.09-1.48). Viral suppression was poor overall (31% had viral loads >400 copies/ml), but was not related to adversity. Adversity showed a robust relationship to depression and substance abuse. Childhood adversity is common, influences the current health of HIV-positive adolescents and youth, and puts their sexual partners at risk for HIV infection. Greater primary prevention of childhood adversity and increased access to support services (e.g., mental health) could reduce risk taking among HIV-positive adolescents and youth. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ursolic acid and luteolin-7-glucoside improve lipid profiles and increase liver glycogen content through glycogen synthase kinase-3.

Science.gov (United States)

Azevedo, Marisa F; Camsari, Cagri; Sá, Carla M; Lima, Cristovao F; Fernandes-Ferreira, Manuel; Pereira-Wilson, Cristina

2010-06-01

In the present study, two phytochemicals - ursolic acid (UA) and luteolin-7-glucoside (L7G) - were assessed in vivo in healthy rats regarding effects on plasma glucose and lipid profile (total cholesterol, HDL and LDL), as well as liver glycogen content, in view of their importance in the aetiology of diabetes and associated complications. Both UA and L7G significantly decreased plasma glucose concentration. UA also significantly increased liver glycogen levels accompanied by phosphorylation of glycogen synthase kinase-3 (GSK3). The increase in glycogen deposition induced by UA (mediated by GSK3) could have contributed to the lower plasma glucose levels observed. Both compounds significantly lowered total plasma cholesterol and low-density lipoprotein levels, and, in addition, UA increased plasma high-density lipoprotein levels. Our results show that UA particularly may be useful in preventable strategies for people at risk of developing diabetes and associated cardiovascular complications by improving plasma glucose levels and lipid profile, as well as by promoting liver glycogen deposition.

Increased serum levels of hyaluronic acid in pregnancies complicated by preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome.

Science.gov (United States)

Osmers, R G; Schütz, E; Diedrich, F; Wehry, B; Krauss, T; Oellerich, M; Kuhn, W

1998-02-01

Fifteen percent of patients who later have hemolysis, elevated liver enzymes, and low platelets syndrome develop initially have nonspecific symptoms. Early diagnosis could ensure adequate obstetric management; however, prognostic biochemical tests are lacking. We hypothesized that elevated hyaluronic acid serum levels might be an early indicator of hemolysis, elevated liver enzymes, and low platelets syndrome because it is known to be a sensitive marker of liver cell function. Hyaluronic acid in serum was measured in patients with normal pregnancies (n = 109) and in those patients with pregnancies complicated by preeclampsia (n = 14) or hemolysis, elevated liver enzymes, and low platelets syndrome (n = 11). A significant increase in hyaluronic acid serum concentrations was observed in patients with hemolysis, elevated liver enzymes, and low platelets syndrome or with preeclampsia (p hyaluronic acid serum levels in hemolysis, elevated liver enzymes, and low platelets syndrome correlated with the clinical severity of the individual course of disease as measured by intensive care unit time (r = 0.72; p hyaluronic acid in preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome are significantly elevated and might play an important diagnostic and prognostic role in patients with hemolysis, elevated liver enzymes, and low platelets syndrome.

Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model.

Science.gov (United States)

Gorden, D Lee; Ivanova, Pavlina T; Myers, David S; McIntyre, J Oliver; VanSaun, Michael N; Wright, J Kelly; Matrisian, Lynn M; Brown, H Alex

2011-01-01

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to cirrhosis. While differences in liver lipids between disease states have been reported, precise composition of phospholipids and diacylglycerols (DAG) at a lipid species level has not been previously described. The goal of this study was to characterize changes in lipid species through progression of human NAFLD using advanced lipidomic technology and compare this with a murine model of early and advanced NAFLD. Utilizing mass spectrometry lipidomics, over 250 phospholipid and diacylglycerol species (DAGs) were identified in normal and diseased human and murine liver extracts. Significant differences between phospholipid composition of normal and diseased livers were demonstrated, notably among DAG species, consistent with previous reports that DAG transferases are involved in the progression of NAFLD and liver fibrosis. In addition, a novel phospholipid species (ether linked phosphatidylinositol) was identified in human cirrhotic liver extracts. Using parallel lipidomics analysis of murine and human liver tissues it was determined that mice maintained on a high-fat diet provide a reproducible model of NAFLD in regards to specificity of lipid species in the liver. These studies demonstrated that novel lipid species may serve as markers of advanced liver disease and importantly, marked increases in DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels characteristic of the disease and specific DAG species might be important lipid signaling molecules in the progression of NAFLD.

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

Science.gov (United States)

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

2015-12-01

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

A wandering liver

International Nuclear Information System (INIS)

Nichols, Brandon W.; Figarola, Maria S.; Standley, Todd B.

2010-01-01

A wandering liver has been described throughout modern medical literature as a rare entity. During the last few years, an increasing number of cases have been reported associated with colonic volvulus. We report a 17-year-old with a hypermobile liver seen on multiple radiographs and CT. The intraoperative findings demonstrated the liver in its normal anatomic position. We suggest that this entity is more common than thought, and the rise in incidence is likely secondary to increased utilization of pre-operative imaging of patients with colonic obstruction. Increased suspicion might result in further increased incidence of this exceedingly rare entity. (orig.)

A wandering liver

Energy Technology Data Exchange (ETDEWEB)

Nichols, Brandon W.; Figarola, Maria S.; Standley, Todd B. [University of South Alabama, Department of Radiology, Mobile, AL (United States)

2010-08-15

A wandering liver has been described throughout modern medical literature as a rare entity. During the last few years, an increasing number of cases have been reported associated with colonic volvulus. We report a 17-year-old with a hypermobile liver seen on multiple radiographs and CT. The intraoperative findings demonstrated the liver in its normal anatomic position. We suggest that this entity is more common than thought, and the rise in incidence is likely secondary to increased utilization of pre-operative imaging of patients with colonic obstruction. Increased suspicion might result in further increased incidence of this exceedingly rare entity. (orig.)

Reversibility of increased formation of catecholamines in patients with alcoholic liver disease

DEFF Research Database (Denmark)

Parlesak, Alexandr; Reisenauer, C.; Biermann, J.

2004-01-01

BACKGROUND: While chronic alcohol abuse has been shown to be associated with increased production of catecholamines, little is known about the reversibility of this increased sympathetic activity and the influence of severity of alcoholic liver disease (ALD). The aim of the present study...... was to investigate whether the increase in urinary excretion rates and plasma levels of catecholamines in alcohol-abusing patients are reversible during prolonged abstinence, especially with respect to the severity of ALD. METHODS: Urinary excretion rates and plasma levels of noradrenaline (NA), adrenaline (A...... concentrations of NA and A were increased in ALD1 and ALD2 about 2-fold, while those of DA were elevated only moderately compared to HC. During exercise under a load of 100 watts, the increases in plasma levels of NA and A with reference to the resting values were nearly identical in all three groups. Already...

Cavernous Transformation of the Portal Vein Might Increase the Risk of Liver Abscess

Directory of Open Access Journals (Sweden)

Xin-Bo Ai

2010-09-01

Full Text Available Cavernous transformation of the portal vein (CTPV is not quite common in adults, and cases with CTPV and acute liver abscess are lacking. We report a patient with CTPV inducing extrahepatic and intrahepatic obstruction, finally leading to acute liver abscess due to bile duct infection. We aim to find out the possible relationship between CTPV and acute liver abscess. A 45-year-old female patient was admitted to our hospital for recurrent upper abdominal pain and distension for one year, aggravated with fever for three years. A diagnosis of CTPV and liver abscess was made by 16-slice computed tomography. Effective antibiotics and drainage were used for this patients, and she was eventually cured. When treating patients with CTPV, extrahepatic and intrahepatic obstruction, one should be aware of the presence of acute liver abscess, and empirical antibiotics might be valuable.

Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Bahnsen, M; Bennett, P

1983-01-01

in patients with alcoholic cirrhosis. This decrease seems to be due to decreased liver function, decreasing hepatic blood flow, and increased portosystemic shunting. Oral testosterone loading may therefore be of prognostic significance in patients with alcoholic liver cirrhosis.......The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...

Autoimmune paediatric liver disease.

Science.gov (United States)

Mieli-Vergani, Giorgina; Vergani, Diego

2008-06-07

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

Alcoholic Liver Disease

Science.gov (United States)

... may be increased in women because their digestive system may be less able to process alcohol, thus increasing the amount of alcohol reaching the liver. Genetic makeup Genetic makeup is thought to be involved because alcoholic liver disease often ...

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases necroinflammation and hepatic stellate cell activation but does not exacerbate experimental liver fibrosis in mice

Energy Technology Data Exchange (ETDEWEB)

Lamb, Cheri L.; Cholico, Giovan N. [Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725 (United States); Pu, Xinzhu [Biomolecular Research Center, Boise State University, Boise, ID 83725 (United States); Hagler, Gerald D. [Department of Biological Sciences, Boise State University, Boise, ID 83725 (United States); Cornell, Kenneth A. [Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725 (United States); Biomolecular Research Center, Boise State University, Boise, ID 83725 (United States); Department of Chemistry and Biochemistry, Boise State University, Boise, ID 83725 (United States); Mitchell, Kristen A., E-mail: kristenmitchell@boisestate.edu [Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725 (United States); Department of Biological Sciences, Boise State University, Boise, ID 83725 (United States)

2016-11-15

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant and high-affinity ligand for the aryl hydrocarbon receptor (AhR). Increasing evidence indicates that AhR signaling contributes to wound healing, which involves the coordinated deposition and remodeling of the extracellular matrix. In the liver, wound healing is attributed to the activation of hepatic stellate cells (HSCs), which mediate fibrogenesis through the production of soluble mediators and collagen type I. We recently reported that TCDD treatment increases the activation of human HSCs in vitro. The goal of this study was to determine how TCDD impacts HSC activation in vivo using a mouse model of experimental liver fibrosis. To elicit fibrosis, C57BL6/male mice were treated twice weekly for 8 weeks with 0.5 ml/kg carbon tetrachloride (CCl{sub 4}). TCDD (20 μg/kg) or peanut oil (vehicle) was administered once a week during the last 2 weeks. Results indicate that TCDD increased liver-body-weight ratios, serum alanine aminotransferase activity, and hepatic necroinflammation in CCl{sub 4}-treated mice. Likewise, TCDD treatment increased mRNA expression of HSC activation and fibrogenesis genes, namely α-smooth muscle actin, desmin, delta-like homolog-1, TGF-β1, and collagen type I. However, TCDD treatment did not exacerbate fibrosis, nor did it increase the collagen content of the liver. Instead, TCDD increased hepatic collagenase activity and increased expression of matrix metalloproteinase (MMP)-13 and the matrix regulatory proteins, TIMP-1 and PAI-1. These results support the conclusion that TCDD increases CCl{sub 4}-induced liver damage and exacerbates HSC activation, yet collagen deposition and the development of fibrosis may be limited by TCDD-mediated changes in extracellular matrix remodeling. - Highlights: • TCDD increased liver damage and inflammation in mice treated with CCl{sub 4}. • TCDD treatment enhanced markers of hepatic stellate cell activation and

Childhood obesity case statement.

Science.gov (United States)

Esposito, Paul W; Caskey, Paul; Heaton, Lisa E; Otsuka, Norman

2013-04-01

The goal of this publication is to raise awareness of the impact of childhood obesity on the musculoskeletal health of children and its potential long-term implications. Relevant articles dealing with musculoskeletal disorders either caused by or worsened by childhood obesity were reviewed through a Pub Med search. Efforts to recognize and combat the childhood obesity epidemic were also identified through Internet search engines. This case statement was then reviewed by the members of the pediatric specialty group of the US Bone and Joint Initiative, which represents an extensive number of organizations dealing with musculoskeletal health. Multiple musculoskeletal disorders are clearly caused by or worsened by childhood obesity. The review of the literature clearly demonstrates the increased frequency and severity of many childhood musculoskeletal disorders. Concerns about the long-term implications of these childhood onset disorders such as pain and degenerative changes into adulthood are clearly recognized by all the member organizations of the US Bone and Joint Initiative. It is imperative to recognize the long-term implications of musculoskeletal disorders caused by or worsened by childhood obesity. It is also important to recognize that the ability to exercise comfortably is a key factor to developing a healthy lifestyle and maintaining a healthy body weight. Efforts to develop reasonable and acceptable programs to increase physical activity by all facets of society should be supported. Further research into the long-term implications of childhood musculoskeletal disorders related to childhood obesity is necessary. Copyright © 2013 Elsevier Inc. All rights reserved.

Metabolic effects of obesity causing disease in childhood.

Science.gov (United States)

Abrams, Pamela; Levitt Katz, Lorraine E

2011-02-01

Childhood obesity is rising to epidemic proportions throughout the world, and much emphasis has been placed on the long-term consequences that can result later, in adulthood. This article reviews the metabolic consequences of obesity that can manifest as disease during the childhood years. Obese children suffer from many disease processes once thought to affect only adults. They can have type 2 diabetes mellitus, and potentially early β cell failure with rapid progression to an insulin requirement. There is a high prevalence of fatty liver disease in obese children, and complications such as steatohepatitis and even cirrhosis can develop during childhood. Visceral fat has been shown to have many different properties than subcutaneous fat, and children with central adiposity can develop the metabolic syndrome with insulin resistance, hypertension, and dyslipidemia. Hyperandrogenism, sleep disturbances, and many types of orthopedic complications can also develop in young children. Physicians should not only warn obese children and their families about the long-term consequences of obesity for which they are at risk in adulthood, they should also screen for the many diseases that may already be present.

Factors influencing liver and spleen volume changes after donor hepatectomy for living donor liver transplantation

Energy Technology Data Exchange (ETDEWEB)

Bae, Ji Hee; Ryeom, Hunku; Song, Jung Hup [Kyungpook National University Hospital, Daegu (Korea, Republic of)

2013-11-15

To define the changes in liver and spleen volumes in the early postoperative period after partial liver donation for living-donor liver transplantation (LDLT) and to determine factors that influence liver and spleen volume changes. 27 donors who underwent partial hepatectomy for LDLT were included in this study. The rates of liver and spleen volume change, measured with CT volumetry, were correlated with several factors. The analyzed factors included the indocyanine green (ICG) retention rate at 15 minutes after ICG administration, preoperative platelet count, preoperative liver and splenic volumes, resected liver volume, resected-to-whole liver volume ratio (LV{sub R}/LV{sub W}), resected liver volume to the sum of whole liver and spleen volume ratio [LV{sub R}/(LV{sub W} + SV{sub 0})], and pre and post hepatectomy portal venous pressures. In all hepatectomy donors, the volumes of the remnant liver and spleen were increased (increased rates, 59.5 ± 50.5%, 47.9 ± 22.6%). The increment rate of the remnant liver volume revealed a positive correlation with LV{sub R}/LV{sub W} (r = 0.759, p < 0.01). The other analyzed factors showed no correlation with changes in liver and spleen volumes. The spleen and remnant liver volumes were increased at CT volumetry performed 2 weeks after partial liver donation. Among the various analyzed factors, LV{sub R}/LV{sub W} influences the increment rate of the remnant liver volume.

Association of decrease in liver triglyceride content with increase in plasma adiponectin levels after pioglitazone treatment in Japanese patients with type 2 diabetes

International Nuclear Information System (INIS)

Nagasawa, Kan; Kaneko, Yoshihito; Taneichi, Haruhito

2010-01-01

Pioglitazone, an insulin-sensitizing thiazolidinedione, has multiple clinical effects including improvement of insulin sensitivity, blood glucose levels and serum lipid profiles, decrease in liver triglyceride (TG) content, and increase in serum adiponectin. However, the correlation and causal relationship between these effects are not fully understood clinically. Therefore, we analyzed these relationships in patients with type 2 diabetes treated with pioglitazone, focusing on changes in liver TG content and serum adiponectin. Thirteen Japanese patients with type 2 diabetes were treated with pioglitazone (15 mg/day) for more than 3 months. Before and after the pioglitazone treatment, liver TG content was measured by magnetic resonance spectroscopy and various clinical variables were also measured. The pioglitazone treatment significantly decreased the liver TG content (-12.9±8.1%, p 2 =0.53, p=0.017), implying increased serum adiponectin may have decreased liver fat content. (author)

Ascorbic acid deficiency increases endotoxin influx to portal blood and liver inflammatory gene expressions in ODS rats.

Science.gov (United States)

Tokuda, Yuki; Miura, Natsuko; Kobayashi, Misato; Hoshinaga, Yukiko; Murai, Atsushi; Aoyama, Hiroaki; Ito, Hiroyuki; Morita, Tatsuya; Horio, Fumihiko

2015-02-01

The aim of this study was to determine whether ascorbic acid (AsA) deficiency-induced endotoxin influx into portal blood from the gastrointestinal tract contributes to the inflammatory changes in the liver. The mechanisms by which AsA deficiency provokes inflammatory changes in the liver were investigated in Osteogenic Disorder Shionogi (ODS) rats (which are unable to synthesize AsA). Male ODS rats (6-wk-old) were fed a diet containing sufficient (300 mg/kg) AsA (control group) or a diet without AsA (AsA-deficient group) for 14 or 18 d. On day 14, the hepatic mRNA levels of acute-phase proteins and inflammation-related genes were significantly higher in the AsA-deficient group than the control group, and these elevations by AsA deficiency were exacerbated on day 18. The serum concentrations of interleukin (IL)-1β and IL-6, which induce acute-phase proteins in the liver, were also significantly elevated on day 14 in the AsA-deficient group compared with the respective values in the control group. IL-1β mRNA levels in the liver, spleen, and lung were increased by AsA deficiency. Moreover, on both days 14 and 18, the portal blood endotoxin concentration was significantly higher in the AsA-deficient group than in the control group, and a significant correlation between serum IL-1β concentrations and portal endotoxin concentrations was found in AsA-deficient rats. In the histologic analysis of the ileum tissues, the number of goblet cells per villi was increased by AsA deficiency. These results suggest that AsA deficiency-induced endotoxin influx into portal blood from the gastrointestinal tract contributes to the inflammatory changes in the liver. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2016-08-26

The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: A combined transcriptomics and metabolomics analysis

NARCIS (Netherlands)

Kleemann, R.; Verschuren, L.; Erk, M.J. van; Nikolsky, Y.; Cnubben, N.H.P.; Verheij, E.R.; Smilde, A.K.; Hendriks, H.F.J.; Zadelaar, A.S.M.; Smith, G.J.; Kaznacheev, V.; Nikolskaya, T.; Melnikov, A.; Hurt-Camejo, E.; Greef, J. van der; Ommen, B. van; Kooistra, T.

2007-01-01

Background: Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver in the evolution of inflammation, we

Split-liver transplantation : An underused resource in liver transplantation

NARCIS (Netherlands)

Rogiers, Xavier; Sieders, Egbert

2008-01-01

Split-liver transplantation is an efficient tool to increase the number of liver grafts available for transplantation. More than 15 years after its introduction only the classical splitting technique has reached broad application. Consequently children are benefiting most from this possibility.

Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

Energy Technology Data Exchange (ETDEWEB)

Obayashi, Yoko, E-mail: youko_oobayashi@ajinomoto.com [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Campbell, Jean S.; Fausto, Nelson [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Yeung, Raymond S. [Department of Surgery, University of Washington School of Medicine, Seattle, WA (United States)

2013-07-19

Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/− mice was not enhanced. •The Tsc2+/− livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/− mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/− mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/− mice was not enhanced. Instead, the Tsc2+/− livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.

Multidisciplinary care of obese children and adolescents for one year reduces ectopic fat content in liver and skeletal muscle.

Science.gov (United States)

Fonvig, Cilius Esmann; Chabanova, Elizaveta; Ohrt, Johanne Dam; Nielsen, Louise Aas; Pedersen, Oluf; Hansen, Torben; Thomsen, Henrik S; Holm, Jens-Christian

2015-12-30

Ectopic fat deposition in liver and skeletal muscle tissue is related to cardiovascular disease risk and is a common metabolic complication in obese children. We evaluated the hypotheses of ectopic fat in these organs could be diminished following 1 year of multidisciplinary care specialized in childhood obesity, and whether this reduction would associate with changes in other markers of metabolic function. This observational longitudinal study evaluated 40 overweight children and adolescents enrolled in a multidisciplinary treatment protocol at the Children's Obesity Clinic, Holbæk, Denmark. The participants were assessed by anthropometry, fasting blood samples (HbA1c, glucose, insulin, lipids, and biochemical variables of liver function), and liver and muscle fat content assessed by magnetic resonance spectroscopy at enrollment and following an average of 12.2 months of care. Univariate linear regression models adjusted for age, sex, treatment duration, baseline degree of obesity, and pubertal developmental stage were used for investigating possible associations. The standard deviation score (SDS) of baseline median body mass index (BMI) was 2.80 (range: 1.49-3.85) and the median age was 14 years (10-17). At the end of the observational period, the 40 children and adolescents (21 girls) significantly decreased their BMI SDS, liver fat, muscle fat, and visceral adipose tissue volume. The prevalence of hepatic steatosis changed from 28 to 20 % (p = 0.26) and the prevalence of muscular steatosis decreased from 75 to 45 % (p = 0.007). Changes in liver and muscle fat were independent of changes in BMI SDS, baseline degree of obesity, duration of treatment, age, sex, and pubertal developmental stage. A 1-year multidisciplinary intervention program in the setting of a childhood obesity outpatient clinic confers a biologically important reduction in liver and muscle fat; metabolic improvements that are independent of the magnitude of concurrent weight loss

Efficacy of liver parenchymal enhancement and liver volume to standard liver volume ratio on Gd-EOB-DTPA-enhanced MRI for estimation of liver function

Energy Technology Data Exchange (ETDEWEB)

Yoneyama, Tomohide; Fukukura, Yoshihiko; Kamimura, Kiyohisa; Takumi, Koji; Umanodan, Aya; Nakajo, Masayuki [Kagoshima University Graduate School of Medical and Dental Sciences, Department of Radiology, Kagoshima City (Japan); Ueno, Shinichi [Kagoshima University Graduate School of Medical and Dental Sciences, Department of Surgical Oncology and Digestive Surgery, Kagoshima City (Japan)

2014-04-15

We aimed to develop and assess the efficacy of a liver function index that combines liver enhancement and liver volume to standard liver volume (LV/SLV) ratio on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. In all, 111 patients underwent a Gd-EOB-DTPA-enhanced MRI, including T1 mapping, before and 20 min after Gd-EOB-DTPA administration. We calculated the following Gd-EOB-DTPA-enhanced MRI-based liver function indices: relative enhancement of the liver, corrected enhancement of the liver-to-spleen ratio, LSC{sub N}20, increase rate of the liver-to-muscle ratio, reduction rate of T1 relaxation time of the liver, ΔR1 of the liver and K{sub Hep}; the indices were multiplied by the LV/SLV ratio. We calculated the correlations between an indocyanine green (ICG) clearance and the Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio, by using Pearson correlation analysis. There were significant correlations between all Gd-EOB-DTPA-enhanced MRI-based liver function indices and ICG clearance (r = -0.354 to -0.574, P < 0.001). All Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio (r = -0.394 to -0.700, P < 0.001) were more strongly correlated with the ICG clearance than those without multiplication by the LV/SLV ratio. Gd-EOB-DTPA-enhanced MRI-based liver function indices that combine liver enhancement and the LV/SLV ratio may more reliably estimate liver function. (orig.)

Increase in hospital admissions for acute childhood asthma in Cape ...

African Journals Online (AJOL)

To determine whether hospital admissions for acute childhood asthma were rising in Cape Town in line with the experience of other countries, Red Cross War Memorial Children's Hospital's records for the period 1978 - 1990 were analysed. These were compared with total admissions for non-surgical causes and lower ...

Advanced glycation end products promote ChREBP expression and cell proliferation in liver cancer cells by increasing reactive oxygen species.

Science.gov (United States)

Chen, Hanbei; Li, Yakui; Zhu, Yemin; Wu, Lifang; Meng, Jian; Lin, Ning; Yang, Dianqiang; Li, Minle; Ding, WenJin; Tong, Xuemei; Su, Qing

2017-08-01

The aim of the study was to elucidate the mechanism by which advanced glycation end products (AGEs) promote cell proliferation in liver cancer cells.We treated liver cancer HepG2 cells with 200 mg/L AGEs or bovine serum albumin (BSA) and assayed for cell viability, cell cycle, and apoptosis. We performed real-time PCR and Western blot analysis for RNA and protein levels of carbohydrate responsive element-binding protein (ChREBP) in AGEs- or BSA-treated HepG2 cells. We analyzed the level of reactive oxygen species (ROS) in HepG2 cells treated with AGEs or BSA.We found that increased S-phase cell percentage and decreased apoptosis contributed to AGEs-induced liver cancer cell proliferation. Real-time PCR and Western blot analysis showed that AGEs stimulated RNA and protein levels of ChREBP, a transcription factor promoting glycolysis and maintaining cell proliferation in liver cancer cells. Intriguingly, the level of ROS was higher in AGEs-treated liver cancer cells. Treating liver cancer cells with antioxidant N-acetyl cystein (NAC) partly blocked AGEs-induced ChREBP expression and cell proliferation.Our results suggest that the AGEs-ROS-ChREBP pathway plays a critical role in promoting ChREBP expression and liver cancer cell proliferation.

Liver

International Nuclear Information System (INIS)

Bernardino, M.E.; Sones, P.J. Jr.; Barton Price, R.; Berkman, W.A.

1984-01-01

Evaluation of the liver for focal lesions is extremely important because the liver is one of the most common sites for metastatic disease. Most patients with metastatic deposits to the liver have a survival rate of about 6 months. Thus, metastatic disease to the liver has an extremely grave prognosis. In the past patients with hepatic lesions had no therapeutic recourse. However, with recent aggressive surgical advances (such as partial hepatectomies) and hepatic artery embolization, survival of patients with hepatic metastases has increased. Thus it is important for noninvasive imaging not only to detect lesions early in their course, but also to give their true hepatic involvement and the extent of the neoplastic process elsewhere in the body. Recent advances in imaging have been rapidly changing over the past 5 years. These changes have been more rapid in computed tomography (CT) and ultrasound than in radionuclide imaging. Thus, the question addressed in this chapter is: What is the relationship of hepatic ultrasound to the other current diagnostic modalities in detecting metastatic liver disease and other focal liver lesions? Also, what is its possible future relationship to nuclear magnetic resonance?

Alternative regression models to assess increase in childhood BMI

OpenAIRE

Beyerlein, Andreas; Fahrmeir, Ludwig; Mansmann, Ulrich; Toschke, André M

2008-01-01

Abstract Background Body mass index (BMI) data usually have skewed distributions, for which common statistical modeling approaches such as simple linear or logistic regression have limitations. Methods Different regression approaches to predict childhood BMI by goodness-of-fit measures and means of interpretation were compared including generalized linear models (GLMs), quantile regression and Generalized Additive Models for Location, Scale and Shape (GAMLSS). We analyzed data of 4967 childre...

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

Science.gov (United States)

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

2018-01-01

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

gamma-Glutamyl transpeptidase overexpression increases metastatic growth of B16 melanoma cells in the mouse liver.

Science.gov (United States)

Obrador, Elena; Carretero, Julian; Ortega, Angel; Medina, Ignacio; Rodilla, Vicente; Pellicer, José A; Estrela, José M

2002-01-01

B16 melanoma (B16M) cells with high glutathione (GSH) content show rapid proliferation in vitro and high metastatic activity in the liver in vivo. gamma-Glutamyl transpeptidase (GGT)-mediated extracellular GSH cleavage and intracellular GSH synthesis were studied in vitro in B16M cells with high (F10) and low (F1) metastatic potential. GGT activity was modified by transfection with the human GGT gene (B16MF1/Tet-GGT cells) or by acivicin-induced inhibition. B16MF1/Tet-GGT and B16MF10 cells exhibited higher GSH content (35 +/- 6 and 40 +/- 5 nmol/10(6) cells, respectively) and GGT activity (89 +/- 9 and 37 +/- 7 mU/10(6) cells, respectively) as compared (P <.05) with B16MF1 cells (10 +/- 3 nmol GSH and 4 mU GGT/10(6) cells). Metastasis (number of foci/100 mm(3) of liver) increased in B16MF1 cells pretreated with GSH ester ( approximately 3-fold, P <.01), and decreased in B16MF1/Tet-GGT and B16MF10 cells pretreated with the GSH synthesis inhibitor L-buthionine (S,R)-sulphoximine ( approximately 5-fold and 2-fold, respectively, P <.01). Liver, kidney, brain, lung, and erythrocyte GSH content in B16MF1/Tet-GGT- or B16MF10-bearing mice decreased as compared with B16MF1- and non-tumor-bearing mice. Organic anion transporting polypeptide 1-independent sinusoidal GSH efflux from hepatocytes increased in B16MF1/Tet-GGT- or B16MF10-bearing mice ( approximately 2-fold, P <.01) as compared with non-tumor-bearing mice. Our results indicate that tumor GGT activity and an intertissue flow of GSH can regulate GSH content of melanoma cells and their metastatic growth in the liver.

A new liver function test using the asialoglycoprotein-receptor system on the liver cell membrane, 3

International Nuclear Information System (INIS)

Hazama, Hiroshi; Kawa, Soukichi; Kubota, Yoshitsugu

1986-01-01

We evaluated the vilidity of a new liver function test using liver scintigraphy based on the asialoglycoprotein (ASGP) receptor system on the liver cell membrane in rats with galactosamine-induced acute liver disorder and those with carbon tetra-chloride-induced chronic liver disorder. Neoglycoprotein (GHSA) produced by combining human serum albumin with 32 galactose units was labeled with 99m Tc and administered (50 μg/100 g body weight) to rats with acute or chronic liver disorder. Clearance curves were produced based on liver scintigrams and analysed using the two-compartment model to obtain parameters. In acute liver disorder, the prolongation of 99m Tc-GHSA clearance and the decrease in ASGP receptor activities correlated well to the increase in serum GOT and the decrease in the esterified to total cholesterol ratio (E/T ratio); in chronic liver disorder, they correlated significantly to the increase in the content of liver hydroxyproline (Hyp) which increased in proportion to the severity of liver fibrosis studied histologically, and to the decrease in the contents of cytochrome P-450 and cytochrome b 5 in liver microsomes. Significant correlation was observed between the prolongation of 99m Tc-GHSA clearance and the decrease in ASGP receptor activities in both acute and chronic liver disorders. These findings indicate that the measurement of 99m Tc-GHSA clearance can be a new liver function test sensitively reflecting the severity of liver damage. (author)

Childhood Adversities Increase the Risk of Psychosis: A Meta-analysis of Patient-Control, Prospective- and Cross-sectional Cohort Studies

Science.gov (United States)

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

Increased plasma levels of microparticles expressing CD39 and CD133 in acute liver injury

DEFF Research Database (Denmark)

Schmelzle, Moritz; Splith, Katrin; Wiuff Andersen, Lars

2013-01-01

BACKGROUND: We have previously demonstrated that CD133 and CD39 are expressed by hematopoietic stem cells (HSC), which are mobilized after liver injury and target sites of injury, limit vascular inflammation, and boost hepatic regeneration. Plasma microparticles (MP) expressing CD39 can block...... sacrificed and plasma MP were isolated by ultracentrifugation. HSC and CD133 MP levels were analyzed by fluorescence-activated cell sorting. Patients were enrolled with acute (n=5) and acute on chronic (n=5) liver injury with matched controls (n=7). Blood was collected at admission and plasma CD133 and CD39...... MP subsets were analyzed by fluorescence-activated cell sorting. RESULTS: HSC and CD133 MP levels were significantly increased only in the plasma of wild-type mice with acetaminophen hepatotoxicity (P

A national prospective study on childhood celiac disease in the Netherlands 1993-2000: an increasing recognition and a changing clinical picture

NARCIS (Netherlands)

Steens, R.F.; Csizmadia, C.G.; George, E.K.; Ninaber, M.K.; Hira Sing, R.A.; Mearin, M.L.

2005-01-01

P10, abdominal pain, and lassitude. The median age at diagnosis also increased. CONCLUSION: The recognition of childhood CD in the Netherlands has increased significantly during the last few years, and the clinical picture has changed as well. Our data may indicate an increasing awareness of the

Factors influencing liver and spleen volume changes after donor hepatectomy for living donor liver transplantation

International Nuclear Information System (INIS)

Bae, Ji Hee; Ryeom, Hunku; Song, Jung Hup

2013-01-01

To define the changes in liver and spleen volumes in the early postoperative period after partial liver donation for living-donor liver transplantation (LDLT) and to determine factors that influence liver and spleen volume changes. 27 donors who underwent partial hepatectomy for LDLT were included in this study. The rates of liver and spleen volume change, measured with CT volumetry, were correlated with several factors. The analyzed factors included the indocyanine green (ICG) retention rate at 15 minutes after ICG administration, preoperative platelet count, preoperative liver and splenic volumes, resected liver volume, resected-to-whole liver volume ratio (LV R /LV W ), resected liver volume to the sum of whole liver and spleen volume ratio [LV R /(LV W + SV 0 )], and pre and post hepatectomy portal venous pressures. In all hepatectomy donors, the volumes of the remnant liver and spleen were increased (increased rates, 59.5 ± 50.5%, 47.9 ± 22.6%). The increment rate of the remnant liver volume revealed a positive correlation with LV R /LV W (r = 0.759, p R /LV W influences the increment rate of the remnant liver volume.

Correlation with liver scintigram, reticuloendothelial function test, plasma endotoxin level and liver function tests in chronic liver diseases. Multivariate analysis

Energy Technology Data Exchange (ETDEWEB)

Ohmoto, Kenji; Yamamoto, Shinichi; Ideguchi, Seiji and others

1989-02-01

Liver scintigrams with Tc-99m phytate were reviewed in a total of 64 consecutive patients, comprising 28 with chronic hepatitis and 36 with liver cirrhosis. Reticuloendothelial (RES) function, plasma endotoxin (Et) levels and findings of general liver function tests were used as reference parameters to determine the diagnostic ability of liver scintigraphy. Multivariate analyses revealed that liver scintigrams had a strong correlation with RES function and Et levels in terms of morphology of the liver and hepatic and bone marrow Tc-99m uptake. General liver function tests revealed gamma globulin to be correlated with hepatic uptake and the degree of splenogemaly on liver scintigrams; and ICG levels at 15 min to be correlated with bone marrow and splenic uptake. Accuracy of liver scintigraphy was 73% for chronic hepatitis, which was inferior to general liver function tests (83%). When both modalities were combined, diangostic accuracy increased to 95%. Liver scintigraphy seems to be useful as a complementary approach. (Namekawa, K).

Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice.

Science.gov (United States)

Kim, In Hee; Xu, Jun; Liu, Xiao; Koyama, Yukinori; Ma, Hsiao-Yen; Diggle, Karin; You, Young-Hyun; Schilling, Jan M; Jeste, Dilip; Sharma, Kumar; Brenner, David A; Kisseleva, Tatiana

2016-08-01

We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between old-aged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or

Ultrasonographic detection of focal liver lesions: increased sensitivity and specificity with microbubble contrast agents

International Nuclear Information System (INIS)

Hohmann, J.; Albrecht, T.; Hoffmann, C.W.; Wolf, K.-J.

2003-01-01

Ultrasonography (US) is the first choice for screening patients with suspected liver lesions. However, due to a lack of contrast agents, US used to be less sensitive and specific compared with computed tomography (CT) and magnet resonance imaging (MRI). The advent of microbubble contrast agents increased both sensitivity and specificity dramatically. Rapid developments of the contrast agents as well as of special imaging techniques were made in recent years. Today numerous different US imaging methods exist which based either on Doppler or on harmonic imaging. They are using the particular behaviour of microbubbles in a sound field which varies depending on the energy of insonation (low/high mechanical index, MI) as well as on the properties of the agent themselves. Apart from just blood pool enhancement some agents have a hepatosplenic specific late phase. US imaging during this late phase using relatively high MI in phase inversion mode (harmonic imaging) or stimulated acoustic emission (SAE; Doppler method) markedly improves the detection of focal liver lesions and is also very helpful for lesion characterisation. With regards to detection, contrast enhanced US performs similarly to CT as shown by recent studies. Early results of studies using low MI imaging and the newer perfluor agents are also showing promising results for lesion detection. Low MI imaging with these agents has the advantage of real time imaging and is particularly helpful for characterisation of focal lesions based on their dynamic contrast behaviour. Apart from the techniques which based on the morphology of liver lesions there were some attempts for the detection of occult metastases or micrometastases by means of liver blood flow changes. Also in this field the use of US contrast agents appears to have advantages over formerly used non contrast-enhanced methods although no conclusive results are available yet

Multimodality postoperative imaging of liver transplantation

International Nuclear Information System (INIS)

Zamboni, Giulia A.; Pedrosa, Ivan; Kruskal, Jonathan B.; Raptopoulos, Vassilios

2008-01-01

Liver transplantation is the only effective and definitive treatment for patients with end-stage liver disease. The shortage of cadaveric livers has lead to the increasing use of split-liver transplantation and living-donor liver transplantation, but the expansion of the donor pool has increased the risk for postoperative vascular and biliary complications. Early recognition of the imaging appearances of the various postoperative complications of liver transplantation is crucial for both graft and patient survival. This review describes the imaging findings of normal and abnormal transplanted liver parenchyma and of vascular and biliary post-transplantation complications. (orig.)

Preoperative Right Portal Vein Embolization in Patients with metastatic liver disease. Metastatic liver volumes after RPVE

International Nuclear Information System (INIS)

Barbaro, B.; Stasi, C.D.I.; Marano, P.; Nuzzo, G.; Vellone, M.; Giuliante, F.

2003-01-01

Purpose:To quantify liver metastases and future remnant liver (FRL) volumes in patients who underwent right portal vein embolization (RPVE) and to evaluate the effects of this procedure on metastase growth. Material and Methods:Nine patients with liver metastases from primary colon (n = 5), rectal lesions (n = 1) and carcinoid tumors (n = 3) underwent spiral CT to evaluate the ratio of the non-tumorous parenchymal volume of the resected liver to that of the whole liver volume (R2). Hand tracing was used to isolate the entire liver, the resected liver and metastase volumes. All patients with R2 > 60% underwent RPVE. Results:FRL exhibited a 101-336 cm3 (average 241 cm3) increase in volume 1 month after RPVE. One patient refused surgery for 2 months and before surgery the increase in volume of the FRL was similar to that of other patients (180.64 cm3). Percent metastases volume from colorectal carcinoma in embolized liver parenchyma increased from 62.4% to 138.4% at 1 month and to 562% at 2 months after RPVE. Metastase volume from carcinoid tumors was unchanged. Conclusion:One month after RPVE, hypertrophy of the FRL is evident. In the embolized liver, there was a progressive increase in metastase volume from colorectal carcinoma while metastase volume from carcinoid tumor was unchanged in embolized and non-embolized liver

Fish oil prevents sucrose-induced fatty liver but exacerbates high-safflower oil-induced fatty liver in ddy mice.

Science.gov (United States)

Yamazaki, Tomomi; Nakamori, Akiko; Sasaki, Eriko; Wada, Satoshi; Ezaki, Osamu

2007-12-01

Diets high in sucrose/fructose or fat can result in hepatic steatosis (fatty liver). We analyzed the effects of dietary fish oil on fatty liver induced by sucrose, safflower oil, and butter in ddY mice. In experiment I, mice were fed a high-starch diet [70 energy% (en%) starch] plus 20% (wt/wt) sucrose in the drinking water or fed a high-safflower oil diet (60 en%) for 11 weeks. As a control, mice were fed a high-starch diet with drinking water. Fish oil (10 en%) was either supplemented or not. Mice supplemented with sucrose or fed safflower oil showed a 1.7-fold or 2.2-fold increased liver triglyceride content, respectively, compared with that of control mice. Fish oil completely prevented sucrose-induced fatty liver, whereas it exacerbated safflower oil-induced fatty liver. Sucrose increased SREBP-1c and target gene messenger RNAs (mRNAs), and fish oil completely inhibited these increases. In experiment II, mice were fed a high-safflower oil or a high-butter diet, with or without fish oil supplementation. Fish oil exacerbated safflower oil-induced fatty liver but did not affect butter-induced fatty liver. Fish oil increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and target CD36 mRNA in safflower oil-fed mice. These increases were not observed in sucrose-supplemented or butter-fed mice. The effects of dietary fish oil on fatty liver differ according to the cause of fatty liver; fish oil prevents sucrose-induced fatty liver but exacerbates safflower oil-induced fatty liver. The exacerbation of fatty liver may be due, at least in part, to increased expression of liver PPARgamma.

Simultaneous liver-pancreas transplantation for cystic fibrosis-related liver disease : A multicenter experience

NARCIS (Netherlands)

Bandsma, R. H. J.; Bozic, M. A.; Fridell, J. A.; Crull, M. H.; Molleston, J.; Avitzur, Y.; Mozer-Glassberg, Y.; Gonzalez-Peralta, R. P.; Hodik, M.; Fecteau, A.; de Angelis, M.; Durie, P.; Ng, V. L.

Background: Diabetes is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). While liver transplantation is well established for CF-related liver disease (CFLD), the role of simultaneous liver pancreas transplantation is less understood. Methods: We polled 81

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

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

Clofibric acid increases the formation of oleic acid in endoplasmic reticulum of the liver of rats.

Science.gov (United States)

Hirose, Akihiko; Yamazaki, Tohru; Sakamoto, Takeshi; Sunaga, Katsuyoshi; Tsuda, Tadashi; Mitsumoto, Atsushi; Kudo, Naomi; Kawashima, Yoichi

2011-01-01

The effects of 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) on the formation of oleic acid (18:1) from stearic acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [¹⁴C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) clofibric acid for 7 days; and the distribution of radiolabeled fatty acids among subcellular organelles, microsomes, peroxisomes, and mitochondria, was estimated on the basis of correction utilizing the yields from homogenates of marker enzymes for these organelles. The radioactivity was mostly localized in microsomes and the radiolabeled fatty acids present in microsomes were significantly increased by the treatment of rats with clofibric acid. The formation of radiolabeled 18:1 in microsomes markedly increased and incorporations of the formed [¹⁴C]18:1 into PC and phosphatidylethanolamine in microsomes were augmented in response to clofibric acid. The [¹⁴C]18:1 incorporated into PC was mostly located at the C-2 position, but not the C-1 position, of PC, and the radioactivity in 18:1 at the C-2 position of PC was strikingly increased by clofibric acid. These results obtained from the in vivo experiments directly link the findings that clofibric acid treatment induces microsomal stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase in the liver and the findings that the treatment with the drug elevated absolute mass and mass proportion of 18:1 at the C-2 position, but not the C-1 position, of PC in the liver together.

Including osteoprotegerin and collagen IV in a score-based blood test for liver fibrosis increases diagnostic accuracy.

Science.gov (United States)

Bosselut, Nelly; Taibi, Ludmia; Guéchot, Jérôme; Zarski, Jean-Pierre; Sturm, Nathalie; Gelineau, Marie-Christine; Poggi, Bernard; Thoret, Sophie; Lasnier, Elisabeth; Baudin, Bruno; Housset, Chantal; Vaubourdolle, Michel

2013-01-16

Noninvasive methods for liver fibrosis evaluation in chronic liver diseases have been recently developed, i.e. transient elastography (Fibroscan™) and blood tests (Fibrometer®, Fibrotest®, and Hepascore®). In this study, we aimed to design a new score in chronic hepatitis C (CHC) by selecting blood markers in a large panel and we compared its diagnostic performance with those of other noninvasive methods. Sixteen blood tests were performed in 306 untreated CHC patients included in a multicenter prospective study (ANRS HC EP 23 Fibrostar) using METAVIR histological fibrosis stage as reference. The new score was constructed by non linear regression using the most accurate biomarkers. Five markers (alpha-2-macroglobulin, apolipoprotein-A1, AST, collagen IV and osteoprotegerin) were included in the new function called Coopscore©. Using the Obuchowski Index, Coopscore© shows higher diagnostic performances than for Fibrometer®, Fibrotest®, Hepascore® and Fibroscan™ in CHC. Association between Fibroscan™ and Coopscore© might avoid 68% of liver biopsies for the diagnosis of significant fibrosis. Coopscore© provides higher accuracy than other noninvasive methods for the diagnosis of liver fibrosis in CHC. The association of Coopscore© with Fibroscan™ increases its predictive value. Copyright © 2012 Elsevier B.V. All rights reserved.

Adrenarche and middle childhood.

Science.gov (United States)

Campbell, Benjamin C

2011-09-01

Middle childhood, the period from 6 to 12 years of age, is defined socially by increasing autonomy and emotional regulation, somatically by the development of anatomical structures for subsistence, and endocrinologically by adrenarche, the adrenal production of dehydroepiandrosterone (DHEA). Here I suggest that DHEA plays a key role in the coordinated development of the brain and body beginning with middle childhood, via energetic allocation. I argue that with adrenarche, increasing levels of circulating DHEA act to down-regulate the release of glucose into circulation and hence limit the supply of glucose which is needed by the brain for synaptogenesis. Furthermore, I suggest the antioxidant properties of DHEA may be important in maintaining synaptic plasticity throughout middle childhood within slow-developing areas of the cortex, including the insula, thamalus, and anterior cingulate cortex. In addition, DHEA may play a role in the development of body odor as a reliable social signal of behavioral changes associated with middle childhood.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

2016-07-19

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

INCREASE OF GLYCOSAMINOGLYCANS AND METALLOPROTEINASES 2 AND 9 IN LIVER EXTRACELLULAR MATRIX ON EARLY STAGES OF EXTRAHEPATIC CHOLESTASIS

Directory of Open Access Journals (Sweden)

Pedro Luiz Rodrigues GUEDES

2014-12-01

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

Serum adiponectin is increased in advancing liver fibrosis and declines with reduction in fibrosis in chronic hepatitis B.

Science.gov (United States)

Hui, Chee-Kin; Zhang, Hai-Ying; Lee, Nikki P; Chan, Weng; Yueng, Yui-Hung; Leung, Kar-Wai; Lu, Lei; Leung, Nancy; Lo, Chung-Mau; Fan, Sheung-Tat; Luk, John M; Xu, Aimin; Lam, Karen S; Kwong, Yok-Lam; Lau, George K K

2007-08-01

Despite the possible role of adiponectin in the pathogenesis of liver cirrhosis, few data have been collected from patients in different stages of liver fibrosis. We studied the role of adiponectin in 2 chronic hepatitis B (CHB)-patient cohorts. Serum adiponectin was quantified by enzyme-linked immunosorbent assay. One-hundred liver biopsy specimens from CHB patients with different stages of fibrosis and 38 paired liver biopsies from hepatitis B e antigen-positive patients randomized to lamivudine (n=15), pegylated interferon alfa-2a (n=15) or pegylated interferon alfa-2a plus lamivudine (n=8) therapy for 48 weeks were assessed. Serum adiponectin was detected at levels ranging over fourfold magnitude with advancing fibrosis stage and correlated positively with fibrosis stage [r=0.45, p<0.001]. CHB patients with stage 0-1 fibrosis had higher composition of high molecular weight (HMW) form of adiponectin when compared with CHB patients with liver cirrhosis [mean+/-SEM 51.2+/-2.1% vs. 40.9+/-1.7%, respectively, p=0.001]. After antiviral therapy, patients with fibrosis reduction had marked decline in serum adiponectin level and increase in HMW form of adiponectin [mean+/-SEM 43.5+/-1.2% vs. 37.0+/-3.0%, respectively, p=0.04]. Serum adiponectin may have a role in fibrosis progression in CHB infection. A marked decline in serum adiponectin after antiviral therapy is associated with fibrosis reduction.

Radiation-induced liver damage

International Nuclear Information System (INIS)

Marcial, V.A.; Santiago-Delpin, E.A.; Lanaro, A.E.; Castro-Vita, H.; Arroyo, G.; Moscol, J.A.; Gomez, C.; Velazquez, J.; Prado, K.

1977-01-01

Due to the recent increase in the use of radiation therapy in the treatment of cancer with or without chemotherapy, the risk of liver radiation damage has become a significant concern for the radiotherapist when the treated tumour is located in the upper abdomen or lower thorax. Clinically evident radiation liver damage may result in significant mortality, but at times patients recover without sequelae. The dose of 3000 rads in 3 weeks to the entire liver with 5 fractions per week of 200 rads each, seems to be tolerated well clinically by adult humans. Lower doses may lead to damage when used in children, when chemotherapy is added, as in recent hepatectomy cases, and in the presence of pre-existent liver damage. Reduced fractionation may lead to increased damage. Increased fractionation, limitation of the dose delivered to the entire liver, and restriction of the high dose irradiation volume may afford protection. With the aim of studying the problems of hepatic radiation injury in humans, a project of liver irradiation in the dog is being conducted. Mongrel dogs are being conditioned, submitted to pre-irradiation studies (haemogram, blood chemistry, liver scan and biopsy), irradiated under conditions resembling human cancer therapy, and submitted to post-irradiation evaluation of the liver. Twenty-two dogs have been entered in the study but only four qualify for the evaluation of all the study parameters. It has been found that dogs are susceptible to liver irradiation damage similar to humans. The initial mortality has been high mainly due to non-radiation factors which are being kept under control at the present phase of the study. After the initial experiences, the study will involve variations in total dose and fractionation, and the addition of anticoagulant therapy for possible prevention of radiation liver injury. (author)

Filtration as the main mechanism of increased protein extravasation in liver cirrhosis

DEFF Research Database (Denmark)

Henriksen, J H; Parving, H H; Lassen, N A

1980-01-01

Transvascular escape rates of albumin and immunoglobulin-G, IgG (TERalb and TERIgG, i.e, the fractions of intravascular mass of albumin and IgG passing to the extravascular space per unit time) were determined simultaneously from the disappearance of intravenously injected 131I-labelled human serum...... albumin and 125I-labelled human IgG in eight patients with cirrhosis of the liver. The mean wedged hepatic venous pressure was 22 mmHg (range 13-34). TERalb and and TERIgG/TERalb ratio was on average 8.4 +/- 0.8%/h (SD), and 7.4 +/- 1.9%/h (SD), respectively and these values are significantly increased...

Importance and significance of liver echotomography in Wilson disease childhood

Energy Technology Data Exchange (ETDEWEB)

Corda, R; Nurchi, A M; Corrias, A; Corda, A; Giagheddu, M; Campisi, G

1987-01-01

We studed the hepatic echography patterns of young patients suffering from Wilson's Disease and compared these with results obtained from laboratory tests and parenchymal biopsy. Eight children, aged between 5 and 12 years (4 males and 4 females), were examined. The symptomatological pattern showed hepatomegaly and liver dysfunction with undetectable or very low serum ceruloplasmine levels and typical aspects of organic copper metabolism. In 50% of cases echography revealed a variable hyperreflection of the whole parenchyma, in connection with the presence of steatosis and aspects of intralobular inflammation. Fine and linear echoes were present, in 50% of the cases, with varying degrees of brightness, which was associated with the presence of fibrotic component or copper granules. Further echographic modifications were less frequent. Echography in close relatives of our patients was observed hepatomegaly and alteration of hepatic reflection associated with fibrotic component. In the evaluation of liver involvement in Wilson's Disease, these findings show that echotomography, when compared to hepatic biopsy, is less efficient in detecting different types of hepatic lesion but on a clinical basis it offers the possibility of evaluating their presence and gravity during the evolutive phase of the illness. This examination, unlike other methods, is completely non invasive; it may easily be repeated and may, in the future, come to be used as more precise diagnostic complement. 30 refs.

Immune mediated liver failure.

Science.gov (United States)

Wang, Xiaojing; Ning, Qin

2014-01-01

Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

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

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

2014-02-01

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

Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells.

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Sayılan Özgün, Gülben; Özgün, Eray; Tabakçıoğlu, Kıymet; Süer Gökmen, Selma; Eskiocak, Sevgi; Çakır, Erol

2017-12-01

Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. In vitro experimental study. HepG2 cells were incubated with 0 (control), 10, 50 and 200 μM of caffeine for 24 hours. Cell viability was evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels were measured by western blotting. We observed a significant increase on apolipoprotein A-1 and paraoxonase-1 protein levels in the cells incubated with 50 µM of caffeine and a significant increase on paraoxonase-1 protein level in the cells incubated with 200 µM of caffeine. Our study showed that caffeine does not change paraoxonase-3 protein level, but the higher doses used in our study do cause an increase in both apolipoprotein A-1 and paraoxonase-1 protein levels in liver cells.

Stress and Obesity in Childhood

OpenAIRE

Koch, Felix-Sebastian

2009-01-01

Childhood obesity is a serious health problem and prevalence increases dramatically around the world, including Sweden. The aim of the current thesis was to examine parents’ and children’s stress in relation to childhood obesity. Parenting stress, social support, parental worries, and serious life events, as well as children’s temperament, self-esteem, body dissatisfaction, saliva cortisol, weight and height were measured to estimate stress and the relation between stress and childhood obesit...

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

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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. Copyright © 2015 Elsevier Inc. All rights reserved.

Volumetric and functional recovery of the remnant liver after major liver resection with prior portal vein embolization : recovery after PVE and liver resection

NARCIS (Netherlands)

van den Esschert, J.W.; de Graaf, W.; van Lienden, K.P.; Busch, O.R.; Heger, M.; van Delden, O.M.; Gouma, D.J.; Bennink, R.J.; Laméris, J.S.; van Gulik, T.M.

2009-01-01

INTRODUCTION: Portal vein embolization is an accepted method to increase the future remnant liver preoperatively. The aim of this study was to assess the effect of preoperative portal vein embolization on liver volume and function 3 months after major liver resection. MATERIALS AND METHODS: This is

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

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Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

2016-09-01

Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Robot-assisted liver resection].

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Aselmann, H; Möller, T; Kersebaum, J-N; Egberts, J H; Croner, R; Brunner, M; Grützmann, R; Becker, T

2017-06-01

Robotic liver resection can overcome some of the limitations of laparoscopic liver surgery; therefore, it is a promising tool to increase the proportion of minimally invasive liver resections. The present article gives an overview of the current literature. Furthermore, the results of a nationwide survey on robotic liver surgery among hospitals in Germany with a DaVinci system used in general visceral surgery and the perioperative results of two German robotic centers are presented.

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

Science.gov (United States)

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

2016-01-01

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

Kisspeptin-10 Enhanced Egg Production in Quails Associated with the Increase of Triglyceride Synthesis in Liver

Directory of Open Access Journals (Sweden)

J. Wu

2013-08-01

Full Text Available Our previous results showed that kisspeptin-10 (Kp-10 injections via intraperitoneal (i.p. once daily for three weeks notably promoted the egg laying rate in quails. In order to investigate the mechanism behind the effects of Kp-10 on enhancing the egg laying rate in birds, this study focused on the alternations of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of age were allocated to three groups randomly, and subjected to 0 (control, Con, 10 nmol (low dosage, L and 100 nmol (high dosage, H Kp-10 injections via i.p. once daily for three weeks, respectively. At d 52, quails were sacrificed and sampled for further analyses. Serum E2 concentration was increased by Kp-10 injections, and reached statistical significance in H group. Serum triglyceride (TG concentrations were increased by 46.7% in L group and 36.8% in H group, respectively, but did not reach statistical significance, and TG contents in liver were significantly elevated by Kp-10 injections in a dose-dependent manner. Serum total cholesterol (Tch concentrations significantly decreased in H group, while in H group the hepatic Tch content was markedly increased. The level of non-esterified fatty acid (NEFA, apolipoprotein A1 and B (apoA1 and apoB were not altered by Kp-10 injections. The genes expression of sterol regulatory element binding protein-1 (SREBP-1, fatty acid synthetase (FAS, apolipoprotein VLDL-II (apoVLDL-II, cholesterol 7α-hydroxylase (CYP7A1 and vitellogenin II (VTG-II were significantly up-regulated by high but not low dosage of Kp-10 injection compared to the control group. However, the expression of SREBP-2, acetyl-CoA carboxylase (ACCα, malic enzyme (ME, stearoyl-CoA (Δ9 desaturase 1 (SCD1, apolipoprotein A1 (apoA1, fatty acid binding protein 2 (FABP2, 3-hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR, estrogen receptor α, β (ERα and β mRNA were not affected by Kp-10 treatment. In line with hepatic mRNA abundance, hepatic SREBP

Increase of peripheral Th17 lymphocytes during acute cellular rejection in liver transplant recipients.

Science.gov (United States)

Fan, Hua; Li, Li-Xin; Han, Dong-Dong; Kou, Jian-Tao; Li, Ping; He, Qiang

2012-12-15

Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+IL-17+ cells were measured by flow cytometry. The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes. Percentages of circulating Th17 cells were compared between the two groups and controls. The levels of circulating CD4+IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56+/-0.43% versus 1.79+/-0.44%, Pblood was positively correlated with the rejection activity index (r=0.79, P=0.0002). Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.

Impact of liver cirrhosis on liver enhancement at Gd-EOB-DTPA enhanced MRI at 3 Tesla

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Verloh, N., E-mail: niklas.verloh@stud.uni-regensburg.de [Department of Radiology, University Hospital Regensburg, Regensburg (Germany); Haimerl, M.; Rennert, J.; Müller-Wille, R.; Nießen, C. [Department of Radiology, University Hospital Regensburg, Regensburg (Germany); Kirchner, G. [Department of Gastroenterology, University Hospital Regensburg, Regensburg (Germany); Scherer, M.N. [Department of Surgery, University Hospital Regensburg, Regensburg (Germany); Schreyer, A.G.; Stroszczynski, C.; Fellner, C.; Wiggermann, P. [Department of Radiology, University Hospital Regensburg, Regensburg (Germany)

2013-10-01

Purpose: The purpose of this study was to assess differences in enhancement effects of liver parenchyma between normal and cirrhotic livers on dynamic, Gd-EOB-DTPA enhanced MRI at 3 T. Materials and methods: 93 patients with normal (n = 54) and cirrhotic liver (n = 39; Child–Pugh class A, n = 18; B, n = 16; C, n = 5) underwent contrast-enhanced MRI with liver specific contrast media at 3 T. T1-weighted volume interpolated breath hold examination (VIBE) sequences with fat suppression were acquired before contrast injection, in the arterial phase (AP), in the late arterial phase (LAP), in the portal venous phase (PVP), and in the hepatobiliary phase (HBP) after 20 min. The relative enhancement (RE) of the signal intensity of the liver parenchyma was calculated for all phases. Results: Mean RE was significantly different among all evaluated groups in the hepatobiliary phase and with increasing severity of liver cirrhosis, a decreasing, but still significant reduction of RE could be shown. Phase depending changes of RE for each group were observed. In case of non-cirrhotic liver or Child–Pugh Score A cirrhosis mean RE showed a significant increase between AP, LAP, PVP and HBP. For Child–Pugh B + C cirrhosis RE increased until PVP, however, there was no change in case of B cirrhosis (p = 0.501) and significantly reduced in case of C cirrhosis (p = 0.043) during HBP. Conclusion: RE of liver parenchyma is negatively affected by increased severity of liver cirrhosis, therefore diagnostic value of HBP could be limited in case of Child Pugh B + C cirrhosis.

Impact of liver cirrhosis on liver enhancement at Gd-EOB-DTPA enhanced MRI at 3 Tesla

International Nuclear Information System (INIS)

Verloh, N.; Haimerl, M.; Rennert, J.; Müller-Wille, R.; Nießen, C.; Kirchner, G.; Scherer, M.N.; Schreyer, A.G.; Stroszczynski, C.; Fellner, C.; Wiggermann, P.

2013-01-01

Purpose: The purpose of this study was to assess differences in enhancement effects of liver parenchyma between normal and cirrhotic livers on dynamic, Gd-EOB-DTPA enhanced MRI at 3 T. Materials and methods: 93 patients with normal (n = 54) and cirrhotic liver (n = 39; Child–Pugh class A, n = 18; B, n = 16; C, n = 5) underwent contrast-enhanced MRI with liver specific contrast media at 3 T. T1-weighted volume interpolated breath hold examination (VIBE) sequences with fat suppression were acquired before contrast injection, in the arterial phase (AP), in the late arterial phase (LAP), in the portal venous phase (PVP), and in the hepatobiliary phase (HBP) after 20 min. The relative enhancement (RE) of the signal intensity of the liver parenchyma was calculated for all phases. Results: Mean RE was significantly different among all evaluated groups in the hepatobiliary phase and with increasing severity of liver cirrhosis, a decreasing, but still significant reduction of RE could be shown. Phase depending changes of RE for each group were observed. In case of non-cirrhotic liver or Child–Pugh Score A cirrhosis mean RE showed a significant increase between AP, LAP, PVP and HBP. For Child–Pugh B + C cirrhosis RE increased until PVP, however, there was no change in case of B cirrhosis (p = 0.501) and significantly reduced in case of C cirrhosis (p = 0.043) during HBP. Conclusion: RE of liver parenchyma is negatively affected by increased severity of liver cirrhosis, therefore diagnostic value of HBP could be limited in case of Child Pugh B + C cirrhosis

Pediatric Non-alcoholic Fatty Liver Disease: Current Thinking.

Science.gov (United States)

Nobili, Valerio; Socha, Piotr

2017-10-31

Non-alcoholic fatty liver disease (NAFLD), an increasingly prevalent paediatric disorder is diagnosed and managed by both paediatric gastroenterologists / hepatologists but also frequently by the general paediatrician. This paper updates recent advances in diagnostic and therapeutic approach which may be applied to everyday practice. Diagnosis of NAFLD takes into account the risk factor profile and is a diagnosis of exclusion. Techniques such as transient elastography and specific biomarkers aimed at improving diagnosis and monitoring of NAFLD need further validation in the paediatric population. Defining the risk to develop cirrhosis seems to be of primary importance already in childhood and a combination of genetic, clinical and environmental factors can help in monitoring and making decisions on therapy. Weight reduction therapy should be the aim of treatment approach but the compliance is poor and pharmacological treatment would be helpful- DHA, some probiotics, vitamin E are to be considered but evidence is not sufficient to recommend widespread use.

Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Bahnsen, M; Bennett, P

1983-01-01

The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...... with wedged-to-free hepatic vein pressure (r = +0.54; P less than 0.01). The increase of testosterone after the load did not correlate significantly with sex hormone-binding globulin (r = +0.35; P greater than 0.05). It is concluded that the hepatic extraction of testosterone is significantly decreased...

Promoting healthy lifestyles and decreasing childhood obesity: increasing physician effectiveness through advocacy.

Science.gov (United States)

Saxe, Jessica Schorr

2011-01-01

Childhood obesity is a well-documented public health crisis. Even many children who are not overweight have inadequate physical activity, poor nutrition, excessive television and other screen time, or some combination thereof. The solution lies in the community. Environmental interventions are among the most effective for improving public health. In addition to addressing lifestyle issues in the office, physicians should advocate for environmental approaches. We can advocate at institutional, local, state, and federal levels through speaking, writing, and collaborating with others. In the United States, the timing is right to synergize with efforts such as the White House Task Force on Childhood Obesity and the Surgeon General's emphasis on changing the national conversation "from a negative one about obesity and illness" to a positive one about health and fitness.

The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.

Science.gov (United States)

Hogg, Kirsten; Wood, Charlotte; McNeilly, Alan S; Duncan, W Colin

2011-01-01

Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS). We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin-like growth factor (IGF) and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5) or testosterone propionate (TP; n = 9) twice weekly (100 mg; i.m) from d62-102 (gestation 147 days). In a novel treatment paradigm, a second cohort received a direct C (n = 4) or TP (20 mg; n = 7) fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (Pfetal intervention (C and TP) led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK) was up-regulated in the fetal controls (Pfetal TP (Pfetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.

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

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Atrayee Banerjee

Full Text Available 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.

Childhood fitness reduces the long-term cardiometabolic risks associated with childhood obesity.

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Schmidt, M D; Magnussen, C G; Rees, E; Dwyer, T; Venn, A J

2016-07-01

The objective of this study was to examine whether childhood cardiorespiratory fitness attenuates or modifies the long-term cardiometabolic risks associated with childhood obesity. The study consisted of a 20-year follow-up of 1792 adults who participated in the 1985 Australian Schools Health and Fitness Survey when they were 7-15 years of age. Baseline measures included a 1.6-km run to assess cardiorespiratory fitness and waist circumference to assess abdominal adiposity. At follow-up, participants attended study clinics where indicators of Metabolic Syndrome (MetS) (waist circumference, blood pressure, fasting blood glucose and lipids) were measured and cardiorespiratory fitness was reassessed using a submaximal graded exercise test. Both high waist circumference and low cardiorespiratory fitness in childhood were significant independent predictors of MetS in early adulthood. The mutually adjusted relative risk of adult MetS was 3.00 (95% confidence interval: 1.85-4.89) for children in the highest (vs lowest) third of waist circumference and 0.64 (95% confidence interval: 0.43-0.96) for children with high (vs low) cardiorespiratory fitness. No significant interaction between waist circumference and fitness was observed, with higher levels of childhood fitness associated with lower risks of adult MetS among those with either low or high childhood waist circumference values. Participants who had both high waist circumference and low cardiorespiratory fitness in childhood were 8.5 times more likely to have MetS in adulthood than those who had low waist circumference and high cardiorespiratory fitness in childhood. Regardless of childhood obesity status, participants with low childhood fitness who increased their relative fitness by adulthood had a substantially lower prevalence of MetS than those who remained low fit. Childhood waist circumference and cardiorespiratory fitness are both strongly associated with cardiometabolic health in later life. Higher levels of

TESTOSTERONE CHANGES IN PATIENTS WITH LIVER CIRRHOSIS BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION AND ITS CORRELATION WITH MELD

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Rodrigo NITSCHE

2014-03-01

Full Text Available Context Hypogonadism is a common clinical situation in male patients with liver cirrhosis. Objectives The aim of the present study was to evaluate the effects of orthotopic liver transplantation on testosterone, free testosterone and sex hormone-binding globulin in male with advanced liver disease and also to determine the relationship of these changes with Model for End-stage Liver Disease (MELD score. Methods In a prospective study, serum levels of testosterone, free testosterone and sex hormone-binding globulin of 30 male adult patients with end-stage liver disease were measured 2 to 4 hours before and 6 months after orthotopic liver transplantation. Results Total testosterone levels increased after orthotopic liver transplantation and the number of patients with normal testosterone levels increased from 18 to 24. Free testosterone mean level in the pre-transplant group was 7.8 pg/mL and increased to 11.5 pg/mL (P = 0.10 and sex hormone-binding globulin level decreased after orthotopic liver transplantation returning to normal levels in MELD ≤18 - group (A (P<0.05. Conclusions Serum level changes of testosterone, free testosterone and sex hormone-binding globulin are more pronounced in cirrhotic males with MELD ≤18. Serum levels of testosterone and free testosterone increase and serum levels of sex hormone-binding globulin decrease after orthotopic liver transplantation.

Rethinking childhood adversity in chronic fatigue syndrome.

Science.gov (United States)

Clark, James E; Davidson, Sean L; Maclachlan, Laura; Newton, Julia L; Watson, Stuart

2018-01-01

Background: Previous studies have consistently shown increased rates of childhood adversity in chronic fatigue syndrome (CFS). However, such aetiopathogenic studies of CFS are potentially confounded by co-morbidity and misdiagnosis particularly with depression. Purpose: We examined the relationship between rates of childhood adversity using two complimentary approaches (1) a sample of CFS patients who had no lifetime history of depression and (2) a modelling approach. Methods: Childhood trauma questionnaire (CTQ) administered to a sample of 52 participants with chronic fatigue syndrome and 19 controls who did not meet criteria for a psychiatric disorder (confirmed using the Structured Clinical Interview for DSM-IV). Subsequently, Mediation Analysis (Baye's Rules) was used to establish the risk childhood adversity poses for CFS with and without depression. Results: In a cohort of CFS patients with depression comprehensively excluded, CTQ scores were markedly lower than in all previous studies and, in contrast to these previous studies, not increased compared with healthy controls. Post-hoc analysis showed that CTQ scores correlated with the number of depressive symptoms during the lifetime worst period of low mood. The probability of developing CFS given a history of childhood trauma is 4%, a two-fold increased risk compared to the general population. However, much of this risk is mediated by the concomitant development of major depression. Conclusions: The data suggests that previous studies showing a relationship between childhood adversity and CFS may be attributable to the confounding effects of co-morbid or misdiagnosed depressive disorder. Abbreviations: CFS: Chronic fatigue syndrome; CTQ: Childhood trauma questionnaire; MDD: Major depressive disorder; CA: Childhood adversity; P : Probability.

[Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation].

Science.gov (United States)

Fischer, H-P

2005-05-01

High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage. Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases

Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

NARCIS (Netherlands)

Geuken, Erwin; Visser, Dorien; Kuipers, Folkert; Blokzijl, Hans; Leuvenink, Henri G. D.; de Jong, Koert P.; Peeters, Paul M. J. G.; Jansen, Peter L. M.; Slooff, Maarten J. H.; Gouw, Annette S. H.; Porte, Robert J.

2004-01-01

BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily

Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

NARCIS (Netherlands)

Geuken, E; Visser, D; Kuipers, F; Blokzijl, H; Leuvenink, HGD; de Jong, KP; Peeters, PMJG; Jansen, PLM; Slooff, MJH; Gouw, ASH; Porte, RJ

2004-01-01

Background/Aims: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. Methods: In 28 liver transplant recipients, bile samples were collected daily

PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

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Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

2013-01-01

Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

A study of human liver ferritin and chicken liver and spleen using Moessbauer spectroscopy with high velocity resolution

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Oshtrakh, M. I., E-mail: oshtrakh@mail.utnet.ru [Ural State Technical University-UPI, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University-UPI, Faculty of Experimental Physics (Russian Federation)

2008-01-15

Lyophilized samples of human liver ferritin and chicken liver and spleen were measured at room temperature using Moessbauer spectroscopy with high velocity resolution. An increase in the velocity resolution of Moessbauer spectroscopy permitted us to increase accuracy and decrease experimental error in determining the hyperfine parameters of human liver ferritin and chicken liver and spleen. Moessbauer spectroscopy with high velocity resolution may be very useful for revealing small differences in hyperfine parameters during biomedical research.

Autoimmune liver serology: current diagnostic and clinical challenges.

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Bogdanos, Dimitrios-P; Invernizzi, Pietro; Mackay, Ian-R; Vergani, Diego

2008-06-07

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and non-specific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians' requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.

Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

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Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

2018-02-09

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

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

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Steven D Kunkel

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

Pediatric obesity and the liver

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Koot, B.G.P.

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of obesity. In some of those with NAFLD, the fat accumulation in the liver will cause inflammation and fibrosis and can ultimately cause liver failure. In addition, in adults it has been established that NAFLD increases the risk of

Dicranostiga leptopodu (Maxim.) Fedde extracts attenuated CCl4-induced acute liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function.

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Tang, Deping; Wang, Fang; Tang, Jinzhou; Mao, Aihong; Liao, Shiqi; Wang, Qin

2017-01-01

Dicranostiga Leptodu (Maxim.) fedde (DLF), a poppy plant, has been reported have many benefits and medicinal properties, including free radicals scavenging and detoxifying. However, the protective effect of DLF extracts against carbon tetrachloride (CCl 4 )-induced damage in mice liver has not been elucidated. Here, we demonstrated that DLF extracts attenuated CCl 4 -induced liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function. In this study, the mice liver damage evoked by CCl 4 was marked by morphology changes, significant rise in lipid peroxidation, as well as alterations of mitochondrial respiratory function. Interestingly, pretreatment with DLF extracts attenuated CCl 4 -induced morphological damage and increasing of lipid peroxidation in mice liver. Additionally, DLF extracts improved mitochondrial function by preventing the disruption of respiratory chain and suppression of mitochondrial Na + K + -ATPase and Ca 2+ -ATPase activity. Furthermore, administration with DLF extracts elevated superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels and maintained the balance of redox status. This results showed that toxic protection effect of DLF extracts on mice liver is mediated by improving mitochondrial respiratory function and keeping the balance of redox status, which suggesting that DLF extracts could be used as potential toxic protection agent for the liver against hepatotoxic agent. Copyright © 2016. Published by Elsevier Masson SAS.

The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.

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Kirsten Hogg

Full Text Available Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS. We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin-like growth factor (IGF and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5 or testosterone propionate (TP; n = 9 twice weekly (100 mg; i.m from d62-102 (gestation 147 days. In a novel treatment paradigm, a second cohort received a direct C (n = 4 or TP (20 mg; n = 7 fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (P<0.05 and the histological presence of fatty liver (P<0.05 independent of central obesity. Additionally, hepatic androgen receptor (AR; P<0.05, glucocorticoid receptor (GR; P<0.05, UDP- glucose ceramide glucosyltransferase (UGCG; P<0.05 and IGF1 (P<0.01 expression were upregulated. The direct fetal intervention (C and TP led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK was up-regulated in the fetal controls (P<0.05 and this was opposed by fetal TP (P<0.05. Hepatic estrogen receptor (ERα; P<0.05 and mitogen activated protein kinase kinase 4 (MAP2K4; P<0.05 were increased following fetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.

Obstructive Sleep Apnea and Non-alcoholic Fatty Liver Disease: Is the Liver Another Target?

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Aibek eMirrakhimov

2012-10-01

Full Text Available Obstructive sleep apnea (OSA is recurrent obstruction of the upper airway during sleep leading to intermittent hypoxia (IH. OSA has been associated with all components of the metabolic syndrome as well as with non-alcoholic fatty liver disease (NAFLD. NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to steatohepatitis (NASH, liver fibrosis and cirrhosis. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Obesity and insulin resistance lead to liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of NAFLD on liver biopsy. However, neither prospective nor interventional studies with continuous positive airway pressure (CPAP treatment have been performed. Studies in a mouse model showed that IH causes triglyceride accumulation in the liver and liver injury as well as hepatic inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1 IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing free fatty acids (FFA flux into the liver; (2 IH up-regulates lipid biosynthetic pathways in the liver; (3 IH induces oxidative stress in the liver; (4 IH up-regulates hypoxia inducible factor 1 alpha and possibly HIF-2 alpha, which may increase hepatic steatosis and induce liver inflammation and fibrosis. However, the role of FFA and different transcription factors in the pathogenesis of IH-induced NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done.

The genetics of childhood obesity and interaction with dietary macronutrients.

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Garver, William S; Newman, Sara B; Gonzales-Pacheco, Diana M; Castillo, Joseph J; Jelinek, David; Heidenreich, Randall A; Orlando, Robert A

2013-05-01

The genes contributing to childhood obesity are categorized into three different types based on distinct genetic and phenotypic characteristics. These types of childhood obesity are represented by rare monogenic forms of syndromic or non-syndromic childhood obesity, and common polygenic childhood obesity. In some cases, genetic susceptibility to these forms of childhood obesity may result from different variations of the same gene. Although the prevalence for rare monogenic forms of childhood obesity has not increased in recent times, the prevalence of common childhood obesity has increased in the United States and developing countries throughout the world during the past few decades. A number of recent genome-wide association studies and mouse model studies have established the identification of susceptibility genes contributing to common childhood obesity. Accumulating evidence suggests that this type of childhood obesity represents a complex metabolic disease resulting from an interaction with environmental factors, including dietary macronutrients. The objective of this article is to provide a review on the origins, mechanisms, and health consequences of obesity susceptibility genes and interaction with dietary macronutrients that predispose to childhood obesity. It is proposed that increased knowledge of these obesity susceptibility genes and interaction with dietary macronutrients will provide valuable insight for individual, family, and community preventative lifestyle intervention, and eventually targeted nutritional and medicinal therapies.

Childhood Maltreatment and Revictimization in a Homeless Population.

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Edalati, Hanie; Krausz, Michael; Schütz, Christian G

2016-09-01

We examined the hypothesis that exposure to childhood maltreatment increases the vulnerability to Adult Victimization (AV) in a homeless population (N = 500). We also investigated the effects of specific types (emotional, physical, and sexual) and cumulative experience of childhood maltreatment on AV, and whether gender moderates these relationships. All three groups with AV experience (emotional, physical, and sexual) indicated higher exposure to childhood abuse and cumulative maltreatment, and those who were sexually victimized as an adult showed higher exposure to childhood neglect. In addition, exposure to childhood maltreatment had type-specific and cumulative effects on AV. Exposure to all types of childhood abuse maintained a strong direct association with AV, regardless of demographic characteristics, including age, ethnicity, marital status, education level, and housing situation. In addition, exposure to physical neglect showed a significant relationship with Adult Sexual Victimization. Cumulative experience of childhood maltreatment was consistently associated with cumulative risk of experiencing AV. Gender had no significant effect on these relationships. Findings suggest that intervention programs in homeless population should consider the history of childhood maltreatment and its characteristics to increase the effectiveness of intervention strategies for AV in this population. © The Author(s) 2015.

[Childhood obesity].

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Chueca, M; Azcona, C; Oyárzabal, M

2002-01-01

Obesity during childhood and adolescence is an increasingly frequent cause for medical consultation. The increase in the prevalence of this disease, which has been considered as an epidemic by the World Health Organisation, is worrying. Obesity is a complex disease, whose aetiology still remains to be clarified due to the numerous factors involved: environmental, genetic, life style and behavioural, neuroendocrinological and metabolic. The persistence of childhood obesity until adulthood significantly increases the risk of suffering from diabetes mellitus, cardiovascular disease, hypertension, cholecystitis and cholelithiasis. Treatment of obesity is complicated and few patients regularly attend follow up examinations. A multidisciplinary team is required to carry out a suitable treatment, composed of paediatricians, dieticians, nurses, psychologists and psychiatrists. Successful treatment of obesity resides in reducing the calorie intake in relation to energy expenditure, and at the time providing instruction in appropriate eating habits and life styles that in the long term will promote the maintenance of the ideal weight.

Liver manifestations of cystic fibrosis

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Akata, Deniz; Akhan, Okan

2007-01-01

Chronic liver disease is one of the major complications of cystic fibrosis (CF). Significant liver disease is seen in 13-25% of children with CF. Improved life expectancy and prolonged follow-up have favored better characterization of the hepatic manifestations of CF and allowed direct observation of an increasing number of liver-related events. Liver disease typically develops in the first decade of life, with the incidence dropping rapidly after the age of 10 years. The wide spectrum of liver disease ranging from asymptomatic gallbladder abnormalities to biliary cirrhosis will be reviewed in this article

Hypothalamic-pituitary-gonadal function in men with liver cirrhosis before and after liver transplantation

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Bruno T. Zacharias

2014-12-01

Full Text Available Objective: To evaluate the influence of end-stage liver disease and orthotopic liver transplantation in the pituitary function and hormone metabolism before and after liver transplantation.Methods: In a prospective study, serum levels of follicle stimulating hormone (FSH, luteinizing hormone (LH, estradiol (E2 and prolactin (PRL of 30 male patients with cirrhosis were determined two to four hours before and six months after liver transplantation. The results were compared according to the Model for End-stage Liver Disease (MELD.Results: male patients with liver cirrhosis have hypogonadism. FSH was normal, but inappropriately low due to androgen failure; E2 and PRL, on their turn, were high. After liver transplantation, FSH and LH levels increased (p 18. The severity of cirrhosis had no influence on FSH, PRL and LH.

Risks of Liver (Hepatocellular) Cancer Screening

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... cancer. Having hepatitis or cirrhosis can increase the risk of developing liver cancer. Anything that increases the ... clinical trials is available from the NCI website . Risks of Liver (Hepatocellular) Cancer Screening Key Points Screening ...

Urinary excretion of water-soluble vitamins increases in streptozotocin-induced diabetic rats without decreases in liver or blood vitamin content.

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Imai, Eri; Sano, Mitsue; Fukuwatari, Tsutomu; Shibata, Katsumi

2012-01-01

It is thought that the contents of water-soluble vitamins in the body are generally low in diabetic patients because large amounts of vitamins are excreted into urine. However, this hypothesis has not been confirmed. To investigate this hypothesis, diabetes was induced in male Wistar rats (6 wk old) by streptozotocin treatment, and they were then given diets containing low, medium or sufficient vitamins for 70 d. The contents of 6 kinds of B-group vitamins, namely vitamin B₁, vitamin B₂, vitamin B₆, vitamin B₁₂, folate and biotin, were determined in the urine, blood and liver. No basic differences among the dietary vitamin contents were observed. The urinary excretion of vitamins was higher in diabetic rats than in control rats. The blood concentrations of vitamin B₁₂ and folate were lowered by diabetes, while, those of vitamin B₁, vitamin B₂, vitamin B₆, and biotin were not. All liver concentrations of vitamins were increased in diabetic rats above those in control rats. These results showed that streptozotocin-induced diabetes increased urinary excretion of water-soluble vitamins, though their blood and liver concentrations were essentially maintained in the rats.

Cytokines and Liver Diseases

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Herbert Tilg

2001-01-01

Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

Retroconversion is a minor contributor to increases in eicosapentaenoic acid following docosahexaenoic acid feeding as determined by compound specific isotope analysis in rat liver.

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Metherel, Adam H; Chouinard-Watkins, Raphaël; Trépanier, Marc-Olivier; Lacombe, R J Scott; Bazinet, Richard P

2017-01-01

Dietary docosahexaenoic acid (DHA, 22:6n-3) not only increases blood and tissue levels of DHA, but also eicosapentaenoic acid (EPA, 20:5n-3). It is generally believed that this increase is due to DHA retroconversion to EPA, however, a slower conversion of α-linolenic acid (ALA, 18:3n-3) derived EPA to downstream metabolic products (i.e. slower turnover of EPA) is equally plausible. In this study, 21-day old Long Evans rats were weaned onto an ALA only or DHA + ALA diet for 12 weeks. Afterwards, livers were collected and the natural abundance 13 C-enrichment was determined by compound specific isotope analysis (CSIA) of liver EPA by isotope ratio mass-spectrometry and compared to dietary ALA and DHA 13 C-enrichment. Isotopic signatures (per mil, ‰) for liver EPA were not different ( p  > 0.05) between the ALA only diet (-25.89 ± 0.39 ‰, mean ± SEM) and the DHA + ALA diet (-26.26 ± 0.40 ‰), suggesting the relative contribution from dietary ALA and DHA to liver EPA did not change. However, with DHA feeding estimates of absolute EPA contribution from ALA increased 4.4-fold (147 ± 22 to 788 ± 153 nmol/g) compared to 3.2-fold from DHA (91 ± 14 to 382 ± 13 nmol/g), respectively. In conclusion, CSIA of liver EPA in rats following 12-weeks of dietary DHA suggests that retroconversion of DHA to EPA is a relatively small contributor to increases in EPA, and that this increase in EPA is largely coming from elongation/desaturation of ALA.

Polyploidization of liver cells.

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Celton-Morizur, Séverine; Desdouets, Chantal

2010-01-01

Eukaryotic organisms usually contain a diploid complement of chromosomes. However, there are a number of exceptions. Organisms containing an increase in DNA content by whole number multiples of the entire set of chromosomes are defined as polyploid. Cells that contain more than two sets of chromosomes were first observed in plants about a century ago and it is now recognized that polyploidy cells form in many eukaryotes under a wide variety of circumstance. Although it is less common in mammals, some tissues, including the liver, show a high percentage of polyploid cells. Thus, during postnatal growth, the liver parenchyma undergoes dramatic changes characterized by gradual polyploidization during which hepatocytes of several ploidy classes emerge as a result of modified cell-division cycles. This process generates the successive appearance of tetraploid and octoploid cell classes with one or two nuclei (mononucleated or binucleated). Liver cells polyploidy is generally considered to indicate terminal differentiation and senescence and to lead both to the progressive loss of cell pluripotency and a markedly decreased replication capacity. In adults, liver polyploidization is differentially regulated upon loss of liver mass and liver damage. Interestingly, partial hepatectomy induces marked cell proliferation followed by an increase in liver ploidy. In contrast, during hepatocarcinoma (HCC), growth shifts to a nonpolyploidizing pattern and expansion of the diploid hepatocytes population is observed in neoplastic nodules. Here we review the current state of understanding about how polyploidization is regulated during normal and pathological liver growth and detail by which mechanisms hepatocytes become polyploid.

Increased prospective health service use for depression among adults with childhood onset bipolar disorder.

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Sala, Regina; Goldstein, Benjamin I; Wang, Shuai; Flórez-Salamanca, Ludwing; Iza, Miren; Blanco, Carlos

2013-11-01

To examine the prospective relationship between age of onset of bipolar disorder and the demographic and clinical characteristics, treatment, new onset of psychiatric comorbidity, and psychosocial functioning among adults with bipolar disorder. As part of the National Epidemiologic Survey on Alcohol and Related Conditions, 1600 adults who met lifetime Statistical Manual of Mental Disorders, 4th edition criteria for bipolar disorder-I (n = 1172) and bipolar disorder-II (n = 428) were included. Individuals were evaluated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV version for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and data were analyzed from Waves 1 and 2, approximately 3 years apart. Individuals with bipolar disorder were divided into three age at onset groups: childhood (adolescence (13-18 years old, n = 396), and adulthood (>19 year old, n = 1017). After adjusting for confounding factors, adults with childhood-onset bipolar disorder were more likely to see a counselor, have been hospitalized, and have received emergency room treatment for depression compared with those with adulthood-onset bipolar disorder. By contrast, there were no differences in the severity of mania or hypomania, new onset of comorbidity, and psychosocial functioning by age of bipolar disorder onset. Childhood-onset bipolar disorder is prospectively associated with seeking treatment for depression, an important proxy for depressive severity. Longitudinal studies are needed in order to determine whether prompt identification, accurate diagnosis, and early intervention can serve to mitigate the burden of childhood onset on the long-term depressive burden of bipolar disorder. Copyright © 2013 Mosby, Inc. All rights reserved.

Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy?

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Chin, Jun L.; Pavlides, Michael; Moolla, Ahmad; Ryan, John D.

2016-01-01

Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care. PMID:27378924

Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.

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Palmisano, Brian T; Le, Thao D; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M

2016-08-01

Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice

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Han-Sol Park

2016-04-01

Full Text Available BackgroundNon-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH, but underlying mechanisms of this prevention are largely unknown.MethodsSeven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day, for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver.ResultsStatin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels.ConclusionStatins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH.

Increased μ-Calpain Activity in Blasts of Common B-Precursor Childhood Acute Lymphoblastic Leukemia Correlates with Their Lower Susceptibility to Apoptosis.

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Anna Mikosik

Full Text Available Childhood acute lymphoblastic leukemia (ALL blasts are characterized by inhibited apoptosis promoting fast disease progress. It is known that in chronic lymphocytic and acute myeloid leukemias the reduced apoptosis is strongly related with the activity of calpain-calpastatin system (CCS composed of cytoplasmic proteases--calpains--performing the modulatory proteolysis of key proteins involved in cell proliferation and apoptosis, and of their endogenous inhibitor--calpastatin. Here, the CCS protein abundance and activity was for the first time studied in childhood ALL blasts and in control bone marrow CD19+ B cells by semi-quantitative flow cytometry and western blotting of calpastatin fragments resulting from endogenous calpain activity. Significantly higher μ-calpain (CAPN1 gene transcription, protein amounts and activity (but not those of m-calpain, with calpastatin amount and transcription of its gene (CAST greatly varying were observed in CD19(+ ALL blasts compared to control cells. Significant inverse relation between the amount/activity of calpain and spontaneous apoptosis was noted. Patients older than 10 years (considered at higher risk displayed increased amounts and activities of blast calpain. Finally, treatment of blasts with the tripeptide calpain inhibitors II and IV significantly and in dose-dependent fashion increased the percentage of blasts entering apoptosis. Together, these findings make the CCS a potential new predictive tool and therapeutic target in childhood ALL.

Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice[S

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Palmisano, Brian T.; Le, Thao D.; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M.

2016-01-01

Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. PMID:27354419

Bioartificial liver and liver transplantation: new modalities for the treatment of liver failure

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DING Yitao

2017-09-01

Full Text Available The main features of liver failure are extensive necrosis of hepatocytes, rapid disease progression, and poor prognosis, and at present, there are no effective drugs and methods for the treatment of liver failure. This article summarizes four treatment methods for liver failure, i.e., medical treatment, cell transplantation, liver transplantation, and artificial liver support therapy, and elaborates on the existing treatment methods. The current medical treatment regimen should be optimized; cell transplantation has not been used in clinical practice; liver transplantation is the most effective method, but it is limited by donor liver shortage and high costs; artificial liver can effectively remove toxic substances in human body. Therefore, this article puts forward artificial liver as a transition for liver transplantation; artificial liver can buy time for liver regeneration or liver transplantation and prolong patients′ survival time and thus has a promising future. The new treatment modality of bioartificial liver combined with liver transplantation may bring good news to patients with liver failure.

Effect of a 10-week weight loss camp on fatty liver disease and insulin sensitivity in obese Danish children

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Grønbæk, Henning; Lange, Aksel; Birkebæk, Niels H

2012-01-01

insulin sensitivity. These abnormalities were mutually related and improved significantly during the camp (P ≤ 0.05). Liver fat improvement was sustained at 12 months. At the 12-month follow-up, 17 of 71 (24%) children maintained the body weight. CONCLUSIONS: This short-term diet and exercise program......BACKGROUND AND OBJECTIVE: Childhood nonalcoholic fatty liver disease (NAFLD) associated with insulin resistance and obesity is a growing problem and increases the risk of cirrhosis, type 2 diabetes mellitus, and cardiovascular complications. We examined the effects of a 10-week "weight loss camp......" residency in obese children on the prevalence and degree of NAFLD and insulin sensitivity with 12-month follow-up. METHODS: At the camp, 117 obese white children (body mass index 28.0 ± 3.6  kg/m, age 12.1 ± 1.3 years) exercised moderately for 1 hour/day and restricted their energy intake to induce weight...

Interactive media for childhood obesity prevention

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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...

Intergenerational violence in Burundi: Experienced childhood maltreatment increases the risk of abusive child rearing and intimate partner violence

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Anselm Crombach

2015-12-01

Full Text Available 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.

Review of liver injury associated with dietary supplements.

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Stickel, Felix; Kessebohm, Kerstin; Weimann, Rosemarie; Seitz, Helmut K

2011-05-01

Dietary supplements (DS) are easily available and increasingly used, and adverse hepatic reactions have been reported following their intake. To critically review the literature on liver injury because of DSs, delineating patterns and mechanisms of injury and to increase the awareness towards this cause of acute and chronic liver damage. Studies and case reports on liver injury specifically because of DSs published between 1990 and 2010 were searched in the PubMed and EMBASE data bases using the terms 'dietary/nutritional supplements', 'adverse hepatic reactions', 'liver injury'; 'hepatitis', 'liver failure', 'vitamin A' and 'retinoids', and reviewed for yet unidentified publications. Significant liver injury was reported after intake of Herbalife and Hydroxycut products, tea extracts from Camellia sinensis, products containing usnic acid and high contents of vitamin A, anabolic steroids and others. No uniform pattern of hepatotoxicity has been identified and severity may range from asymptomatic elevations of serum liver enzymes to hepatic failure and death. Exact estimates on how frequent adverse hepatic reactions occur as a result of DSs cannot be provided. Liver injury from DSs mimicking other liver diseases is increasingly recognized. Measures to reduce risk include tighter regulation of their production and distribution and increased awareness of users and professionals of the potential risks. © 2011 John Wiley & Sons A/S.

Liver transplantation:Yesterday,today and tomorrow

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Osman Abbasoglu

2008-01-01

With the advances in technical skills,management of postoperative complications and improvements in immunosuppressive drugs,liver transplantation is the standard treatment for many patients with chronic liver disease.Today,shortage of donor organs seems to be the major limiting factor for the application of liver transplantation.This review focuses on five issues that are challenging to clinical practice of liver transplantation and relevant to gastroenterologists.These include living donor liver transplantation,recurrent viral hepatitis,non-heart-beating donors,hepatocellular carcinoma,and ABO incompatible livertransplantation.Living donor and non-heart beating donor transplantations were initiated as a solution to increase the donor organ pool and it is expected that there will be an increase in the number of these donors.Recurrent hepatitis C and hepatocellular carcinoma following liver transplantation are among major problems and ongoing research in these diseases may lead to better outcomes in these recipients.

Nondiffuse fatty infiltration of the liver: Does the uptake of iron-oxide increase or decrease at SPIO-enhanced MR imaging?

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Onoda, Hideko; Ito, Katsuyoshi; Tanabe, Masahiro; Shimizu, Ayame; Matsunaga, Naofumi

2011-01-01

Purpose: To clarify whether the uptake of SPIO increases or decreases in areas of fatty change compared with surrounding areas of nonfatty change at SPIO-enhanced MR imaging. Materials and methods: Approval for this retrospective study was obtained from our institutional review board. This study included 14 patients with nondiffuse fatty infiltration of the liver who underwent SPIO-enhanced MR imaging. Additionally, 30 patients without nondiffuse fatty infiltration of the liver were also evaluated. Results: Among 14 patients, areas of fatty change showed relatively high signal intensity in 7 patents, indicating decreased uptake of SPIO in areas of fatty change. In these 7 patients, 4 had mild cirrhosis and 3 did not have cirrhosis. The mean percentage of signal intensity loss (42%) of fatty areas was significantly lower (p < 0.007) than that of adjacent areas of nonfatty change (52%). In the remaining 7 of 14 patients, areas of fatty change showed relatively low signal intensity, indicating increased uptake of SPIO in areas of fatty change. Among these 7 patients, 6 had advanced cirrhosis. The mean percentage of signal intensity loss (47%) of fatty areas was significantly higher (p < 0.008) than that of adjacent areas of nonfatty change (31%). Conclusion: The uptake of SPIO generally decreased in areas of fatty change compared with normal liver parenchyma at SPIO-enhanced MR imaging. However, in patients with advanced cirrhosis, areas of fatty change shows relatively low signal intensity because the uptake of SPIO in surrounding areas of nonfatty change severely decreased probably due to liver fibrosis.

Metformin increases liver accumulation of vitamin B12 - An experimental study in rats

DEFF Research Database (Denmark)

Greibe, E; Miller, J W; Foutouhi, S H

2013-01-01

AIMS/HYPOTHESIS: Patients treated with metformin exhibit low levels of plasma vitamin B(12) (B(12)), and are considered at risk for developing B(12) deficiency. In this study, we investigated the effect of metformin treatment on B(12) uptake and distribution in rats. METHODS: Sprague Dawley rats (n...... that metformin has no decreasing effect on the B(12) absorption. CONCLUSIONS/INTERPRETATION: These results show that metformin treatment increases liver accumulation of B(12), thereby resulting in decreases in circulating B(12) and kidney accumulation of the vitamin. Our data questions whether the low plasma B......(12) observed in patients treated with metformin reflects impaired B(12) status, and rather suggests altered tissue distribution and metabolism of the vitamin....

Pediatric Non-Alcoholic Fatty Liver Disease

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Haley Bush

2017-06-01

Full Text Available Abstract: With the increase in the prevalence of obesity, non-alcoholic fatty liver disease (NAFLD has become among the leading causes of chronic liver disease in the pediatric age group. Once believed to be a “two-hit process”, it is now clear that the actual pathophysiology of NAFLD is complex and involves multiple pathways. Moreover, NAFLD is not always benign, and patients with non-alcoholic steatohepatitis (NASH are at increased risk of developing advanced stages of liver disease. It has also been shown that NAFLD is not only a liver disease, but is also associated with multiple extrahepatic manifestations, including cardiovascular diseases, type 2 diabetes, and low bone mineral density. Although the data is scarce in the pediatric population, some studies have suggested that long-term mortality and the requirement of liver transplantation will continue to increase in patients with NAFLD. More studies are needed to better understand the natural history of NAFLD, especially in the pediatric age group.

Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities

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Jun-Ho Lee

2015-01-01

Full Text Available Euglycemia is the ultimate goal in diabetes care to prevent complications. However, the benefits of euglycemia in type 2 diabetes are controversial because near-euglycemic subjects show higher mortality than moderately hyperglycemic subjects. We previously reported that euglycemic-diabetic rats on calorie-control lose a critical liver weight (LW compared with hyperglycemic rats. Here, we elucidated the molecular mechanisms underlying the loss of LW in euglycemic-diabetic rats and identified a potential risk in achieving euglycemia by calorie-control. Sprague-Dawley diabetic rats generated by subtotal-pancreatectomy were fed a calorie-controlled diet for 7 weeks to achieve euglycemia using 19 kcal% (19R or 6 kcal% (6R protein-containing chow or fed ad libitum (19AL. The diet in both R groups was isocaloric/kg body weight to the sham-operated group (19S. Compared with 19S and hyperglycemic 19AL, both euglycemic R groups showed lower LWs, increased autophagy, and increased AMPK and caspase-3 and decreased mTOR activities. Though degree of insulin deficiency was similar among the diabetic rats, Akt activity was lower, and PTEN activity was higher in both R groups than in 19AL whose signaling patterns were similar to 19S. In conclusion, euglycemia achieved by calorie-control is deleterious in insulin deficiency due to increased autophagy and apoptosis in the liver via AMPK and caspase-3 activation.

Effect of 6-Month Calorie Restriction and Exercise on Serum and Liver Lipids and Markers of Liver Function

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Larson-Meyer, D. Enette; Newcomer, Bradley R.; Heilbronn, Leonie K.; Volaufova, Julia; Smith, Steven R.; Alfonso, Anthony J.; Lefevre, Michael; Rood, Jennifer C.; Williamson, Donald A.; Ravussin, Eric

2009-01-01

objective Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Methods and Procedures Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m2) were randomized to “control (CO)” = 100% energy requirements; “CR” = 25%; “caloric restriction and increased structured exercise (CR+EX)”= 12.5% CR + 12.5% increase in energy expenditure through exercise; or “low-calorie diet (LCD)” = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. Results At baseline, increased liver lipid content (by MRS) correlated (P triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. Discussion CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD. PMID:18421281

The relationship between HbA(1c) and fasting plasma glucose in patients with increased plasma liver enzyme measurements

DEFF Research Database (Denmark)

Christiansen, R; Rasmussen, L Melholt; Nybo, H

2012-01-01

levels of increased liver enzyme concentrations. Methods:  Data from 10 065 patients with simultaneous measurement of HbA(1c) , venous fasting plasma glucose, alanine aminotransferase and γ-glutamyl transferase were extracted from our laboratory database. Correlations were investigated in four patient...

Hepatic Toxicity After Radioembolization of the Liver Using {sup 90}Y-Microspheres: Sequential Lobar Versus Whole Liver Approach

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Seidensticker, Ricarda; Seidensticker, Max; Damm, Robert; Mohnike, Konrad [Universitaetsklinikum Magdeburg, Klinik fuer Radiologie and Nuklearmedizin (Germany); Schuette, Kerstin; Malfertheiner, Peter [Universitaetsklinikum Magdeburg, Klinik fuer Gastroenterologie, Hepatologie und Infektiologie (Germany); Buskirk, Mark Van [Data Reduction (United States); Pech, Maciej; Amthauer, Holger; Ricke, Jens, E-mail: jens.ricke@med.ovgu.de [Universitaetsklinikum Magdeburg, Klinik fuer Radiologie and Nuklearmedizin (Germany)

2012-10-15

Purpose: {sup 90}Y-radioembolization (RE) is a promising technique for delivering high doses of radiation to liver tumors but may result in compromise of liver function. To gain further perspective, we evaluated the toxicity rates of sequential lobar versus 'whole liver' {sup 90}Y-radioembolization. Methods: Thirty-four patients with liver malignancy in noncirrhotic livers were included; {sup 90}Y-radioembolization was performed as either whole liver or sequential lobar treatment in 17 patients each. Standard clinical and liver specific laboratory parameters as well as MR imaging before treatment and at follow-up (6 and 12 weeks) after radioembolization were evaluated for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE). Volumetry of the liver, tumor, and spleen and measurement of portal vein diameter also were performed. Results: Three months after whole liver RE, 14 liver-related grade 3/4 events were recorded versus 2 events after sequential lobar treatment (P < 0.05). Three patients treated with whole liver RE suffered from radioembolization-induced liver disease (REILD). Pathological increases in bilirubin at 3 months were observed for the whole liver group only (52.3 vs. 18.7 {mu}mol/l, P = 0.012). Total liver volume did not change significantly in either group, but shrinkage of the initially treated hepatic lobe with compensatory hypertrophy of the subsequently treated lobe was observed in the sequential lobar group (P < 0.05). Portal vein diameter increased significantly in whole liver-treated patients only (+17% vs. +6.6%, P = 0.043). Conclusions: Noncirrhotic patients undergoing sequential lobar radioembolization had less hepatic toxicity compared to whole liver embolization. The sequential approach should be the preferred strategy.

Regenerative medicine using dental pulp stem cells for liver diseases.

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Ohkoshi, Shogo; Hara, Hajime; Hirono, Haruka; Watanabe, Kazuhiko; Hasegawa, Katsuhiko

2017-02-06

Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes. A point worthy of special mention is that dental pulp can be obtained from deciduous teeth during childhood and can be subsequently harvested when necessary after deposition in a tooth bank. MSCs have not only a regenerative capacity but also act in an anti-inflammatory manner via paracrine mechanisms. Promising efficacies and difficulties with the use of MSC derived from teeth are summarized in this review.

Calcium signaling in liver.

Science.gov (United States)

Gaspers, Lawrence D; Thomas, Andrew P

2005-01-01

In hepatocytes, hormones linked to the formation of the second messenger inositol 1,4,5-trisphosphate (InsP3) evoke transient increases or spikes in cytosolic free calcium ([Ca2+]i), that increase in frequency with the agonist concentration. These oscillatory Ca2+ signals are thought to transmit the information encoded in the extracellular stimulus to down-stream Ca2+-sensitive metabolic processes. We have utilized both confocal and wide field fluorescence microscopy techniques to study the InsP3-dependent signaling pathway at the cellular and subcellular levels in the intact perfused liver. Typically InsP3-dependent [Ca2+]i spikes manifest as Ca2+ waves that propagate throughout the entire cytoplasm and nucleus, and in the intact liver these [Ca2+]i increases are conveyed through gap junctions to encompass entire lobular units. The translobular movement of Ca2+ provides a means to coordinate the function of metabolic zones of the lobule and thus, liver function. In this article, we describe the characteristics of agonist-evoked [Ca2+]i signals in the liver and discuss possible mechanisms to explain the propagation of intercellular Ca2+ waves in the intact organ.

Synthetic bedding and wheeze in childhood.

Science.gov (United States)

Ponsonby, Anne-Louise; Dwyer, Terence; Kemp, Andrew; Cochrane, Jennifer; Couper, David; Carmichael, Allan

2003-01-01

The reasons for the increase in childhood asthma over time are unclear. The indoor environment is of particular concern. An adverse role for synthetic bedding on asthma development in childhood has been suggested by cross-sectional studies that have found an association between synthetic pillow use and childhood wheeze. Prospective data on infant bedding have not been available. Bedding data at 1 month of age were available from an infant survey for children who were participating in a 1995 follow-up study (N = 863; 78% traced). The 1995 follow-up was embedded in a larger cross-sectional survey involving 6,378 seven year olds in Tasmania (N = 92% of eligible). Outcome measures included respiratory symptoms as defined in the International Study of Asthma and Allergies in Childhood protocol. Frequent wheeze was defined as more than 12 wheeze episodes over the past year compared with no wheeze. Synthetic pillow use at 1 month of age was associated with frequent wheeze at age 7 (adjusted relative risk [aRR] = 2.5; 95% confidence interval [CI] = 1.2-5.5) independent of childhood exposure. Current synthetic pillow and quilt use was strongly associated with frequent wheeze (aRR = 5.2; CI = 1.3-20.6). Substantial trends were evident for an association of increasing number of synthetic bedding items with frequent wheeze and with increasing wheeze frequency. Among children with asthma, the age of onset of asthma occurred earlier if synthetic bedding was used in infancy. In this cohort, synthetic bedding was strongly and consistently associated with frequent childhood wheeze. The association did not appear to be attributable to bedding choice as part of an asthma management strategy.

Higher Mortality in registrants with sudden model for end-stage liver disease increase: Disadvantaged by the current allocation policy.

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Massie, Allan B; Luo, Xun; Alejo, Jennifer L; Poon, Anna K; Cameron, Andrew M; Segev, Dorry L

2015-05-01

Liver allocation is based on current Model for End-Stage Liver Disease (MELD) scores, with priority in the case of a tie being given to those waiting the longest with a given MELD score. We hypothesized that this priority might not reflect risk: registrants whose MELD score has recently increased receive lower priority but might have higher wait-list mortality. We studied wait-list and posttransplant mortality in 69,643 adult registrants from 2002 to 2013. By likelihood maximization, we empirically defined a MELD spike as a MELD increase ≥ 30% over the previous 7 days. At any given time, only 0.6% of wait-list patients experienced a spike; however, these patients accounted for 25% of all wait-list deaths. Registrants who reached a given MELD score after a spike had higher wait-list mortality in the ensuing 7 days than those with the same resulting MELD score who did not spike, but they had no difference in posttransplant mortality. The spike-associated wait-list mortality increase was highest for registrants with medium MELD scores: specifically, 2.3-fold higher (spike versus no spike) for a MELD score of 10, 4.0-fold higher for a MELD score of 20, and 2.5-fold higher for a MELD score of 30. A model incorporating the MELD score and spikes predicted wait-list mortality risk much better than a model incorporating only the MELD score. Registrants with a sudden MELD increase have a higher risk of short-term wait-list mortality than is indicated by their current MELD score but have no increased risk of posttransplant mortality; allocation policy should be adjusted accordingly. © 2015 American Association for the Study of Liver Diseases.

Liver Fibrosis: Current Principles of Diagnosis

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A.K. Duda

2014-09-01

Full Text Available Liver fibrosis — a natural consequence of almost all liver diseases of any origin. We are faced with a number of standard stereotype processes that take place in the liver tissue. Mostly it is the processes of chronic inflammation, which oppose the processes of liver tissue regeneration. The basis of imbalance between the processes of fibrosis and regeneration is an accumulation of extracellular matrix. Liver fibrosis in its development leads to liver cirrhosis, hepatocellular carcinoma, and the increase in morbidity rate is observed worldwide. Furthermore, the process is genetically determined, but modifiable factors play an important role in the progression of this disease. Current data indicate the possibility of reversible liver fibrosis.

Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of nonalcoholic fatty liver disease

Science.gov (United States)

Obesity is often associated with a cluster of increased health risks collectively known as "Metabolic Syndrome" (MS). MS is often accompanied by development of fatty liver. Sometimes fatty liver results in damage leading to reduced liver function, and need for a transplant. This condition is known...

Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

Science.gov (United States)

Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

2016-07-26

Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

Postprandial hepatic volume change: spiral CT evaluation in case of liver cirrhosis

International Nuclear Information System (INIS)

Rho, Kwang Suk; Moon, Jang Il; Ko, Myong Kwan; Byun, Joo Nam; Kim, Young Suk; Kim, Young Chol; Oh, Jae Hee

1999-01-01

To investigate the usefulness of evaluating liver cirrhosis through the measurement of liver volume. In a control group(20 normal subjects) and 20 cirrhotic patients, variations in liver volume before and after a meal were obtained. A case-control study was conducted between the two groups. In the control group, the range of increased liver volume after the meal was 67-186ml. Mean increased liver volume was 119.3ml, the range of percentage increase was 6-12.4% and the mean percentage increase was 9.89%. In cirrhotic patients, the range of increased liver volume after the meal was 1-20ml. Mean increase liver volume was 6.9ml, the range of percentage increase was 0-1.9% and the mean percentage increase was 0.65%. Compared with the control group, cirrhotic patients showed a much smaller increase in liver volume(p<0.01). Difference in variation of liver volume between a control group and cirrhotic patients before and after a meal can be used for the evaluation of liver cirrhosis

Correlation of liver enzymes and sonographic findings with pulsatile index of middle cerebral and basilar arteries in nonalcoholic fatty liver

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Gholamreza Rezamand

2014-04-01

Conclusion: Considering the increase of cerebral arteries PI in advanced liver disease, absence of increase in vascular PI of patients in the present study could be attributed to the short duration of disease from diagnosis to perform TCD, lack of advanced liver involvement (absence of liver dysfunction and the response effect to treatment before the TCD. Therefore, to assess vascular changes over time, repeating the TCD with assess other parameters such as Fibroscan and K18 factor that has more compatibility of liver function, could help to understand the pathophysiology of liver diseases and its effect on vascular resistance.

Age dependence of rat liver function measurements

DEFF Research Database (Denmark)

Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

1989-01-01

Changes in the galactose elimination capacity, the capacity of urea-N synthesis and antipyrine clearance were studied in male Wistar rats at the age of 8, 20 and 44 weeks. Further, liver tissue concentrations of microsomal cytochrome P-450, microsomal protein and glutathione were measured. All...... liver function measurements increased from the age of 8 to 44 weeks when expressed in absolute values. In relation to body weight, these function measurements were unchanged or reduced from week 8 to week 20. At week 44, galactose elimination capacity and capacity of urea-N synthesis related to body...... weight were increased by 10% and 36%, respectively, and antipyrine plasma clearance was reduced to 50%. Liver tissue concentrations of microsomal cytochrome P-450 and microsomal protein increased with age when expressed in absolute values, but were unchanged per g liver, i.e., closely related to liver...

Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

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Oliveira C.P.M.S.

2006-01-01

Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

Using multiphoton fluorescence lifetime imaging to characterize liver damage and fluorescein disposition in liver in vivo

Science.gov (United States)

Thorling, Camilla A.; Studier, Hauke; Crawford, Darrell; Roberts, Michael S.

2016-03-01

Liver disease is the fifth most common cause of death and unlike many other major causes of mortality, liver disease rates are increasing rather than decreasing. There is no ideal measurement of liver disease and although biopsies are the gold standard, this only allows for a spot examination and cannot follow dynamic processes of the liver. Intravital imaging has the potential to extract detailed information over a larger sampling area continuously. The aim of this project was to investigate whether multiphoton and fluorescence lifetime imaging microscopy could detect early liver damage and to assess whether it could detect changes in metabolism of fluorescein in normal and diseased livers. Four experimental groups were used in this study: 1) control; 2) ischemia reperfusion injury; 3) steatosis and 4) steatosis with ischemia reperfusion injury. Results showed that multiphoton microscopy could visualize morphological changes such as decreased fluorescence of endogenous fluorophores and the presence of lipid droplets, characteristic of steatosis. Fluorescence lifetime imaging microscopy showed increase in NADPH in steatosis with and without ischemia reperfusion injury and could detect changes in metabolism of fluorescein to fluorescein monoglurcuronide, which was impaired in steatosis with ischemia reperfusion injury. These results concluded that the combination of multiphoton microscopy and fluorescence lifetime imaging is a promising method of assessing early stage liver damage and that it can be used to study changes in drug metabolism in the liver as an indication of liver disease and has the potential to replace the traditional static liver biopsy currently used.

Increased Expression of Cytotoxic T-Lymphocyte-Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure

DEFF Research Database (Denmark)

Khamri, Wafa; Abeles, Robin D; Hou, Tie Zheng

2017-01-01

, hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays. RESULTS: Peripheral blood...... were found to have increased concentrations of soluble B7 compared to sera from controls. Necrotic human primary hepatocytes exposed to acetaminophen, but not hepatic sinusoidal endothelial cells and biliary epithelial cells from patients with ALF, secreted high levels of soluble B7. Sera from mice...... with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells. CONCLUSIONS: Peripheral CD4+T cells from patients with ALF have increased...

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

Science.gov (United States)

Kim, Min Ah; Yi, Jaehee

2014-12-01

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

Adverse childhood experience and asthma onset: a systematic review.

Science.gov (United States)

Exley, Daniel; Norman, Alyson; Hyland, Michael

2015-06-01

Adverse childhood experiences such as abuse and neglect are associated with subsequent immune dysregulation. Some studies show an association between adverse childhood experiences and asthma onset, although significant disparity in results exists in the published literature. We aimed to review available studies employing a prospective design that investigates associations between adverse childhood experience and asthma. A search protocol was developed and studies were drawn from four electronic journal databases. Studies were selected in accordance with pre-set inclusion criteria and relevant data were extracted. 12 studies, assessing data from a total of 31 524 individuals, were identified that investigate the impact of a range of adverse childhood experiences on the likelihood of developing asthma. Evidence suggests that chronic stress exposure and maternal distress in pregnancy operate synergistically with known triggers such as traffic-related air pollution to increase asthma risk. Chronic stress in early life is associated with an increased risk of asthma onset. There is evidence that adverse childhood experience increases the impact of traffic-related air pollution and inconsistent evidence that adverse childhood experience has an independent effect on asthma onset. Copyright ©ERS 2015.

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

Science.gov (United States)

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.

Interleukin 17, Produced by γδ T Cells, Contributes to Hepatic Inflammation in a Mouse Model of Biliary Atresia and Is Increased in Livers of Patients.

Science.gov (United States)

Klemann, Christian; Schröder, Arne; Dreier, Anika; Möhn, Nora; Dippel, Stephanie; Winterberg, Thomas; Wilde, Anne; Yu, Yi; Thorenz, Anja; Gueler, Faikah; Jörns, Anne; Tolosa, Eva; Leonhardt, Johannes; Haas, Jan D; Prinz, Immo; Vieten, Gertrud; Petersen, Claus; Kuebler, Joachim F

2016-01-01

Biliary atresia (BA) is a rare disease in infants, with unknown mechanisms of pathogenesis. It is characterized by hepatobiliary inflammatory, progressive destruction of the biliary system leading to liver fibrosis, and deterioration of liver function. Interleukin (IL) 17A promotes inflammatory and autoimmune processes. We studied the role of IL17A and cells that produce this cytokine in a mouse model of BA and in hepatic biopsy samples from infants with BA. We obtained peripheral blood and liver tissue specimens from 20 patients with BA, collected at the time of Kasai portoenterostomy, along with liver biopsies from infants without BA (controls). The tissue samples were analyzed by reverse transcription quantitative polymerase chain reaction (PCR), in situ PCR, and flow cytometry analyses. BA was induced in balb/cAnNCrl mice by rhesus rotavirus infection; uninfected mice were used as controls. Liver tissues were collected from mice and analyzed histologically and by reverse transcriptase PCR; leukocytes were isolated, stimulated, and analyzed by flow cytometry and PCR analyses. Some mice were given 3 intraperitoneal injections of a monoclonal antibody against IL17 or an isotype antibody (control). Livers from rhesus rota virus-infected mice with BA had 7-fold more Il17a messenger RNA than control mice (P = .02). γδ T cells were the exclusive source of IL17; no T-helper 17 cells were detected in livers of mice with BA. The increased number of IL17a-positive γδ T cells liver tissues of mice with BA was associated with increased levels of IL17A, IL17F, retinoid-orphan-receptor C, C-C chemokine receptor 6, and the IL23 receptor. Mice that were developing BA and given antibodies against IL17 had lower levels of liver inflammation and mean serum levels of bilirubin than mice receiving control antibodies (191 μmol/L vs 78 μmol/L, P = .002). Liver tissues from patients with BA had 4.6-fold higher levels of IL17 messenger RNA than control liver tissues (P = .02

Prevalence of childhood asthma in Korea: international study of asthma and allergies in childhood.

Science.gov (United States)

Lee, Sang-Il

2010-04-01

Childhood asthma is a major concern because it leads to more hospital visits and a heavy economic burden. Proper management and prevention strategies for childhood asthma must be based on correct evaluation of prevalence and risk factors for its development. In Korea, nationwide studies were conducted in 1995 and 2000 on students from 68 elementary schools (age, 6-12 years) and junior high schools (age, 12-15 years) by the Korean Academy of Pediatric Allergy and Respiratory Diseases. We used the Korean version of the International Study of Asthma and Allergies in Childhood (ISAAC) written and video questionnaires at the same schools during the same period (October-November). The prevalence of asthma in junior high school children seemed to increase over 5 years. However, in elementary school children, the prevalence of asthma symptoms decreased, although the prevalence of 'diagnosis of asthma, ever' and 'treatment of asthma, last 12 months' increased. In addition, it was found that various factors, such as obesity, passive smoking, dietary habits, raising pets at home, and fever/antibiotic use during infancy were associated with childhood asthma. When prevalence of asthma in Korea was compared with that in different regions, the prevalence changes in the 6-7 years age group did not seem to be consistent between regions, whereas similar trends were observed among children aged 13-14 years. To conduct another epidemiological study to evaluate the time trend over time, a third nationwide survey is planned in 2010, and we anticipate ISAAC Phase 3 will explore recent changes in the prevalence of childhood asthma and assess its risk factors in Korean children. On the basis of accurate data on the current status of childhood asthma in 2010, we will be able to establish proper management strategies.

Alcoholic liver cirrhosis increases the risk of left ventricular diastolic dysfunction

Czech Academy of Sciences Publication Activity Database

Brotánek, J.; Ort, Michael; Kubánek, M.; Stiborová, M.

2013-01-01

Roč. 34, Suppl.2 (2013), s. 64-70 ISSN 0172-780X R&D Projects: GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z50110509 Keywords : left ventricular diastolic dysfunction * cirrhosis * liver * alcohol Subject RIV: FH - Neurology Impact factor: 0.935, year: 2013

Severe childhood malnutrition

DEFF Research Database (Denmark)

Bhutta, Zulfiqar A; Berkley, James A; Bandsma, Robert H J

2017-01-01

The main forms of childhood malnutrition occur predominantly in children malnutrition. Here, we use...... the term 'severe malnutrition' to describe these conditions to better reflect the contributions of chronic poverty, poor living conditions with pervasive deficits in sanitation and hygiene, a high prevalence of infectious diseases and environmental insults, food insecurity, poor maternal and fetal...... nutritional status and suboptimal nutritional intake in infancy and early childhood. Children with severe malnutrition have an increased risk of serious illness and death, primarily from acute infectious diseases. International growth standards are used for the diagnosis of severe malnutrition and provide...

Increasing socioeconomic inequality in childhood undernutrition in urban India: trends between 1992-93, 1998-99 and 2005-06.

Science.gov (United States)

Kumar, Abhishek; Kumari, Divya; Singh, Aditya

2015-10-01

This article examines the trends and pattern in socioeconomic inequality in stunting, underweight and wasting among children aged inequality in childhood undernutrition in urban India has increased over the study period. The salient findings of this study call for separate programmes targeting the children of lower socioeconomic groups in urban population of India. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.

Increased Incidence and Altered Risk Demographics of Childhood Lead Poisoning: Predicting the Impacts of the CDC’s 5 µg/dL Reference Value in Massachusetts (USA)

Science.gov (United States)

Handler, Phoebe; Brabander, Daniel

2012-01-01

In May 2012, the CDC adopted a new sliding scale reference value for childhood lead poisoning, reducing the former 10 µg/dL benchmark by half. Using Massachusetts (MA) as a model state, we estimated the change in the population of 9–47 month-olds at risk for lead poisoning. We then examined the impact of the 5 µg/dL reference value on the demographic characteristics of lead risk in MA communities. We find that the new CDC benchmark will lead to a 1470% increase in childhood lead poisoning cases among 9–47 month-olds in MA, with nearly 50% of the examined communities experiencing an increased prevalence of lead poisoning. Further, the top 10 MA communities with BLLs ≥5 µg/dL have significantly fewer foreign-born residents and significantly larger white populations than the highest risk communities formerly identified by the MA Childhood Lead Poisoning Prevention Program. The CDC’s new 5 µg/dL lead poisoning benchmark will drastically increase the number of children with elevated BLLs and alter the distribution and demographics high-risk communities in MA. PMID:23202824

Observation of Liver Color Scan

Energy Technology Data Exchange (ETDEWEB)

Choe, Y K; Ahn, S B [Yonsei University College of Medicine, Seoul (Korea, Republic of)

1969-09-15

In the past few years, scintigraphy has become increasingly important in clinical practice, and the use of a color-printing technique has permitted a more accurate interpretation of the scan image. Our liver color scintigrams consist of 51 hepatomas, 35 liver cirrhosis, 22 liver abscesses, 10 hepatitis and other 13 cases of the liver diseases which were clinically and pathologically diagnosed at Severance Hospital, Yonsei Univ. since Feb. 1969 through Sept. 1969. These scintigrams have been analyzed in terms of various pathologic morphology, such as size, shape, margin of the liver, distribution of radioactivity, and shape of the space occupying lesions. The results are as follows: 1) Enlargement of the liver was the most common finding in the diseased livers. The Rt. lobe enlargement was particularly prominent in the liver abscess. 2) Irregular distribution of radioactivity in the liver (so called mottling) was present in 78% of hepatoma, while it was seen only in 31% of liver abscesses. 3) Liver cirrhosis tends to show perihilar accumulation of the isotope (57%). 4) The deformity of the lower most angle of the Rt. lobe, and the Lt. lateral margin of the Lt. lobe was also impressive throughout the cases (74-95% of all diseased livers). 5) The frequency of visualization of the spleen was influenced by the size of space occupying lesions and the amount of functioning liver. 6) Differentiation between the liver abscess and hepatoma seems to be possible on scintigram, when shape an margin of defect and patterns of distribution of radioactivity in the remaining liver are clearly demonstrated.

Observation of Liver Color Scan

International Nuclear Information System (INIS)

Choe, Y. K.; Ahn, S. B.

1969-01-01

In the past few years, scintigraphy has become increasingly important in clinical practice, and the use of a color-printing technique has permitted a more accurate interpretation of the scan image. Our liver color scintigrams consist of 51 hepatomas, 35 liver cirrhosis, 22 liver abscesses, 10 hepatitis and other 13 cases of the liver diseases which were clinically and pathologically diagnosed at Severance Hospital, Yonsei Univ. since Feb. 1969 through Sept. 1969. These scintigrams have been analyzed in terms of various pathologic morphology, such as size, shape, margin of the liver, distribution of radioactivity, and shape of the space occupying lesions. The results are as follows: 1) Enlargement of the liver was the most common finding in the diseased livers. The Rt. lobe enlargement was particularly prominent in the liver abscess. 2) Irregular distribution of radioactivity in the liver (so called mottling) was present in 78% of hepatoma, while it was seen only in 31% of liver abscesses. 3) Liver cirrhosis tends to show perihilar accumulation of the isotope (57%). 4) The deformity of the lower most angle of the Rt. lobe, and the Lt. lateral margin of the Lt. lobe was also impressive throughout the cases (74-95% of all diseased livers). 5) The frequency of visualization of the spleen was influenced by the size of space occupying lesions and the amount of functioning liver. 6) Differentiation between the liver abscess and hepatoma seems to be possible on scintigram, when shape an margin of defect and patterns of distribution of radioactivity in the remaining liver are clearly demonstrated.

Computational Modeling in Liver Surgery

Directory of Open Access Journals (Sweden)

Bruno Christ

2017-11-01

Full Text Available The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.

Molecular and clinical characterization of a series of patients with childhood-onset lysosomal acid lipase deficiency. Retrospective investigations, follow-up and detection of two novel LIPA pathogenic variants.

Science.gov (United States)

Pisciotta, Livia; Tozzi, Giulia; Travaglini, Lorena; Taurisano, Roberta; Lucchi, Tiziano; Indolfi, Giuseppe; Papadia, Francesco; Di Rocco, Maja; D'Antiga, Lorenzo; Crock, Patricia; Vora, Komal; Nightingale, Scott; Michelakakis, Helen; Garoufi, Anastasia; Lykopoulou, Lilia; Bertolini, Stefano; Calandra, Sebastiano

2017-10-01

Childhood/Adult-onset Lysosomal Acid Lipase Deficiency (LAL-D) is a recessive disorder due to loss of function variants of LAL, the enzyme which hydrolyses cholesteryl esters, derived from internalized apoB containing lipoproteins. The disease is characterized by multi-organ involvement including the liver, spleen, intestine and cardiovascular system. The aim of this study was the clinical and molecular characterization of 14 (13 unrelated) previously unreported patients with childhood-onset LAL-D. Data collected included clinical and laboratory investigations, liver imaging, liver biopsy and LIPA gene analysis. The response to lipid-lowering medications, liver transplantation and enzyme replacement therapy (ERT) was reported for some patients. LAL-D was suspected at 4.4 ± 3.3 years of age for the presence of hepatomegaly, elevated serum transaminases and hypercholesterolemia, and was confirmed by liver biopsy/imaging and LAL assay. The follow up period ranged from 3 to 40 years (mean 7.8 ± 4.0 years in 13 cases). Patients treated with statins with or without ezetimibe showed 28% reduction of plasma LDL-cholesterol without a tangible effect on liver enzymes; some patients receiving ERT showed normalized lipoprotein profile and transaminase levels. The common c.894G > A variant was observed in homozygosity or compound heterozygosity in 10 patients. We found seven previously reported variants: p.(Trp140*), p.(Arg218*), p.(Gly266*), p.(Thr288Ile), p.(Leu294Ser), p.(His295Tyr) and p.(Gly342Arg) and two novel variants: p.(Asp345Asn), affecting the LAL catalytic triad, and c.229+3A > C, affecting splicing. Homozygosity for p.(Thr288Ile) or c.229+3A > C was associated with a severe phenotype. This study provides additional data on the features of childhood-onset LAL-D and describes two novel pathogenic variants of the LIPA gene. Copyright © 2017. Published by Elsevier B.V.

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

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Jelena Marinić

2016-01-01

Full Text Available 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.

Birth characteristics and childhood carcinomas.

Science.gov (United States)

Johnson, K J; Carozza, S E; Chow, E J; Fox, E E; Horel, S; McLaughlin, C C; Mueller, B A; Puumala, S E; Reynolds, P; Von Behren, J; Spector, L G

2011-10-25

Carcinomas in children are rare and have not been well studied. We conducted a population-based case-control study and examined associations between birth characteristics and childhood carcinomas diagnosed from 28 days to 14 years during 1980-2004 using pooled data from five states (NY, WA, MN, TX, and CA) that linked their birth and cancer registries. The pooled data set contained 57,966 controls and 475 carcinoma cases, including 159 thyroid and 126 malignant melanoma cases. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). White compared with 'other' race was positively associated with melanoma (OR=3.22, 95% CI 1.33-8.33). Older maternal age increased the risk for melanoma (OR(per 5-year age increase)=1.20, 95% CI 1.00-1.44), whereas paternal age increased the risk for any carcinoma (OR=1.10(per 5-year age increase), 95% CI 1.01-1.20) and thyroid carcinoma (OR(per 5-year age increase)=1.16, 95% CI 1.01-1.33). Gestational age birth weight, and birth order were not significantly associated with childhood carcinomas. This exploratory study indicates that some birth characteristics including older parental age and low gestational age may be related to childhood carcinoma aetiology.

Cumulative childhood stress and autoimmune diseases in adults.

Science.gov (United States)

Dube, Shanta R; Fairweather, DeLisa; Pearson, William S; Felitti, Vincent J; Anda, Robert F; Croft, Janet B

2009-02-01

To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0-8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p or=2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses.

DILI (drug induced liver injury in a 9-month-old infant: a rare case of phenobarbital-induced hepatotoxicity

Directory of Open Access Journals (Sweden)

Anna Paola Pinna

2013-04-01

Full Text Available Phenobarbital is one of the most commonly prescribed antiepileptic drugs in childhood, but it can rarely cause serious adverse effects, such as hepatotoxicity that includes a broad clinical spectrum (from isolate hypertransaminasemia to acute liver failure. We describe a case of DILI in a 9-month-old infant caused by chronic therapy with phenobarbital.

An energy-saving development initiative increases birth rate and childhood malnutrition in rural Ethiopia.

Directory of Open Access Journals (Sweden)

Mhairi A Gibson

2006-04-01

Full Text Available Evolutionary life history theory predicts that, in the absence of contraception, any enhancement of maternal condition can increase human fertility. Energetic trade-offs are likely to be resolved in favour of maximizing reproductive success rather than health or longevity. Here we find support for the hypothesis that development initiatives designed to improve maternal and child welfare may also incur costs associated with increased family sizes if they do not include a family planning component.Demographic and anthropometric data were collected in a rural Ethiopian community benefiting from a recent labour-saving development technology that reduces women's energetic expenditure (n = 1,976 households. Using logistic hazards models and general linear modelling techniques, we found that whilst infant mortality has declined, the birth rate has increased, causing greater scarcity of resources within households.This study is, to our knowledge, the first to demonstrate a link between a technological development intervention and an increase in both birth rate and childhood malnutrition. Women's nutritional status was not improved by the energy-saving technology, because energy was diverted into higher birth rates. We argue that the contribution of biological processes to increased birth rates in areas of the developing world without access to modern contraception has been overlooked. This highlights the continued need for development programmes to be multisectoral, including access to and promotion of contraception.

Maternal Employment and Childhood Obesity

DEFF Research Database (Denmark)

Gwozdz, Wencke; Sousa-Poza, Alfonso; Reisch, Lucia

2013-01-01

The substantial increase in female employment rates in Europe over the past two decades has often been linked in political and public rhetoric to negative effects on child development, including obesity. We analyse this association between maternal employment and childhood obesity using rich...... on obesity's main drivers: calorie intake and physical activity. Our analysis provides little evidence for any association between maternal employment and childhood obesity, diet or physical activity....

Maternal Employment and Childhood Obesity

DEFF Research Database (Denmark)

Gwozdz, Wencke; Sousa-Poza, Alfonso; Reisch, Lucia

The substantial increase in female employment rates in Europe over the past two decades has often been linked in political and public rhetoric to negative effects on child development, including obesity. We analyse this association between maternal employment and childhood obesity using rich...... on obesity's main drivers: calorie intake and physical activity. Our analysis provides little evidence for any association between maternal employment and childhood obesity, diet or physical activity....

Effects of elastase on fatty liver

International Nuclear Information System (INIS)

Ogura, Kazuo; Shimizu, Yoshikazu; Hihara, Masafumi; Ando, Hideki; Nishiyama, Masateru; Tano, Hironobu

1984-01-01

Elastase (Elaszym 6T) was administered, in addition to the dietary instruction, to three patients with fatty liver. CT scanning revealed marked improvement in fatty liver. Transaminase levels returned to normal, total cholesterol levels tended to decrease, and HDL-cholesterol levels tended to increase. These results suggest that elastase is effective in the treatment of fatty liver. (Namekawa, K.)

Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience.

Directory of Open Access Journals (Sweden)

Ricky H Bhogal

2011-03-01

Full Text Available Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples.

Liver Disease in the Alcoholic

OpenAIRE

Szilagyi, Andrew

1986-01-01

The problem of liver damage in alcoholic patients is widespread. This review discusses hepatic damage on the basis of a histologic classification of increasing severity. In the early stages, or with compensated cirrhosis, clinical and laboratory findings may not accurately reflect hepatic involvement. Furthermore, there exists a group of alcoholic patients in whom liver disease may be caused by factors other than alcohol. Nevertheless, in most patients with liver disease, certain biochemical ...

Liver transplant for cholestatic liver diseases.

Science.gov (United States)

Carrion, Andres F; Bhamidimarri, Kalyan Ram

2013-05-01

Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT. Copyright © 2013 Elsevier Inc. All rights reserved.

Liver transplant

Science.gov (United States)

Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

Autophagy and Liver Ischemia-Reperfusion Injury

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Raffaele Cursio

2015-01-01

Full Text Available Liver ischemia-reperfusion (I-R injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is found in normal and diseased liver. Although depending on the type of ischemia, warm and/or cold, the dynamic process of liver I-R results mainly in adenosine triphosphate depletion and in production of reactive oxygen species (ROS, leads to both, a local ischemic insult and an acute inflammatory-mediated reperfusion injury, and results finally in cell death. This process can induce liver dysfunction and can increase patient morbidity and mortality after liver surgery and hemorrhagic shock. Whether autophagy protects from or promotes liver injury following warm and/or cold I-R remains to be elucidated. The present review aims to summarize the current knowledge in liver I-R injury focusing on both the beneficial and the detrimental effects of liver autophagy following warm and/or cold liver I-R.

Childhood obesity: causes and consequences.

Science.gov (United States)

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.

Childhood obesity: causes and consequences

Directory of Open Access Journals (Sweden)

Krushnapriya Sahoo

2015-01-01

Full Text Available 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.

Non-invasive assessment of the liver using imaging

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Thorling Thompson, Camilla; Wang, Haolu; Liu, Xin; Liang, Xiaowen; Crawford, Darrell H.; Roberts, Michael S.

2016-12-01

Chronic liver disease causes 2,000 deaths in Australia per year and early diagnosis is crucial to avoid progression to cirrhosis and end stage liver disease. There is no ideal method to evaluate liver function. Blood tests and liver biopsies provide spot examinations and are unable to track changes in function quickly. Therefore better techniques are needed. Non-invasive imaging has the potential to extract increased information over a large sampling area, continuously tracking dynamic changes in liver function. This project aimed to study the ability of three imaging techniques, multiphoton and fluorescence lifetime imaging microscopy, infrared thermography and photoacoustic imaging, in measuring liver function. Collagen deposition was obvious in multiphoton and fluorescence lifetime imaging in fibrosis and cirrhosis and comparable to conventional histology. Infrared thermography revealed a significantly increased liver temperature in hepatocellular carcinoma. In addition, multiphoton and fluorescence lifetime imaging and photoacoustic imaging could both track uptake and excretion of indocyanine green in rat liver. These results prove that non-invasive imaging can extract crucial information about the liver continuously over time and has the potential to be translated into clinic in the assessment of liver disease.

Enlarged Liver

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... of liver damage. Medicinal herbs. Certain herbs, including comfrey, ma huang and mistletoe, can increase your risk ... herbs to avoid include germander, chaparral, senna, mistletoe, comfrey, ma huang, valerian root, kava, celandine and green ...

Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

International Nuclear Information System (INIS)

Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

2013-01-01

Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication

Childhood abuse and suicidal ideation in a cohort of pregnant Peruvian women.

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Zhong, Qiu-Yue; Wells, Anne; Rondon, Marta B; Williams, Michelle A; Barrios, Yasmin V; Sanchez, Sixto E; Gelaye, Bizu

2016-10-01

Childhood abuse is a major global and public health problem associated with a myriad of adverse outcomes across the life course. Suicide is one of the leading causes of mortality during the perinatal period. However, few studies have assessed the relationship between experiences of childhood abuse and suicidal ideation in pregnancy. We sought to examine the association between exposure to childhood abuse and suicidal ideation among pregnant women. A cross-sectional study was conducted among 2964 pregnant women attending prenatal clinics in Lima, Peru. Childhood abuse was assessed using the Childhood Physical and Sexual Abuse Questionnaire. Depression and suicidal ideation were assessed using the Patient Health Questionnaire-9 scale. Logistic regression procedures were performed to estimate adjusted odds ratios and 95% confidence intervals adjusted for potential confounders. Overall, the prevalence of childhood abuse in this cohort was 71.8% and antepartum suicidal ideation was 15.8%. The prevalence of antepartum suicidal ideation was higher among women who reported experiencing any childhood abuse compared to those reporting none (89.3% vs 10.7%, P suicidal ideation. Women who experienced both physical and sexual childhood abuse had much higher odds of suicidal ideation (adjusted odds ratio, 4.04; 95% confidence interval, 2.88-5.68). Women who experienced any childhood abuse and reported depression had 3.44-fold (3.44, adjusted odds ratio; 95% confidence interval, 1.84-6.43) increased odds of suicidal ideation compared with depressed women with no history of childhood abuse. Finally, the odds of suicidal ideation increased with increased number of childhood abuse events experienced (P value for linear trend suicidal ideation. It is important for clinicians to be aware of the potential increased risk of suicidal behaviors among pregnant women with a history of childhood physical and sexual abuse. Copyright © 2016 Elsevier Inc. All rights reserved.

Prenatal programming of childhood overweight and obesity.

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Huang, Jennifer S; Lee, Tiffany A; Lu, Michael C

2007-09-01

To review the scientific evidence for prenatal programming of childhood overweight and obesity, and discuss its implications for MCH research, practice, and policy. A systematic review of observational studies examining the relationship between prenatal exposures and childhood overweight and obesity was conducted using MOOSE guidelines. The review included literature posted on PubMed and MDConsult and published between January 1975 and December 2005. Prenatal exposures to maternal diabetes, malnutrition, and cigarette smoking were examined, and primary study outcome was childhood overweight or obesity as measured by body mass index (BMI) for children ages 5 to 21. Four of six included studies of prenatal exposure to maternal diabetes found higher prevalence of childhood overweight or obesity among offspring of diabetic mothers, with the highest quality study reporting an odds ratio of adolescent overweight of 1.4 (95% CI 1.0-1.9). The Dutch famine study found that exposure to maternal malnutrition in early, but not late, gestation was associated with increased odds of childhood obesity (OR 1.9, 95% CI 1.5-2.4). All eight included studies of prenatal exposure to maternal smoking showed significantly increased odds of childhood overweight and obesity, with most odds ratios clustering around 1.5 to 2.0. The biological mechanisms mediating these relationships are unknown but may be partially related to programming of insulin, leptin, and glucocorticoid resistance in utero. Our review supports prenatal programming of childhood overweight and obesity. MCH research, practice, and policy need to consider the prenatal period a window of opportunity for obesity prevention.

Identification Of Inequalities In The Selection Of Liver Surgery For Colorectal Liver Metastases In Sweden.

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Norén, A; Sandström, P; Gunnarsdottir, K; Ardnor, B; Isaksson, B; Lindell, G; Rizell, M

2018-04-01

Liver resection for colorectal liver metastases offers a 5-year survival rate of 25%-58%. This study aimed to analyze whether patients with colorectal liver metastases undergo resection to an equal extent and whether selection factors play a role in the selection process. Data were retrieved from the Swedish Colorectal Cancer Registry (2007-2011) for colorectal cancer and colorectal liver metastases. The patients identified were linked to the Swedish Registry of Liver and Bile surgery and the National Patient Registry to identify whether liver surgery or ablative treatment was performed. Analyses for age, sex, type of primary tumor and treating hospital (university, county, or district), American Society of Anesthesiologists class, and radiology for detection of metastatic disease were performed. Of 28,355 patients with colorectal cancer, 21.6% (6127/28,355) presented with liver metastases. Of the patients with liver metastases, 18.5% (1134/6127) underwent liver resection or ablation. The cumulative proportion of liver resection/ablation was 4% (1134/28,355) of all colorectal cancer. If "not bowel resected" were excluded, the proportion slightly increased to 4.7% (1134/24,262). Around 15% of the patients with metastases were registered as referrals for liver surgery. In a multivariable analysis patients treated at a university hospital for primary tumor were more frequently surgically treated for liver metastases (p 70 years and those with American Society of Anesthesiologists class >2 underwent liver resection less frequently. Magnetic resonance imaging of the liver was more often used in diagnostic work-up in men. Patients with colorectal liver metastases are unequally treated in Sweden, as indicated by the low referral rate. The proximity to a hepatobiliary unit seems important to enhance the patient's chances of being offered liver surgery.

Multilevel Determinants of Childhood Obesity

OpenAIRE

Chang, Yen-Jung

2012-01-01

The prevalence of obesity among US children and adolescents has rapidly increased in the past several decades, and the epidemic of childhood obesity is currently a serious public health concern in the United States. This dissertation consists of three studies examining individual- and neighborhood-level determinants of childhood obesity. The study area was Los Angeles County in California. Our first study examined the effects of maternal employment, individual socioeconomic status (SES), and ...

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

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Gemma Aragonès

Full Text Available 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.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.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.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.

Surveillance of hepatic late adverse effects in a large cohort of long-term survivors of childhood cancer: prevalence and risk factors

NARCIS (Netherlands)

Mulder, Renée L.; Kremer, Leontien C. M.; Koot, Bart G. P.; Benninga, Marc A.; Knijnenburg, Sebastiaan L.; van der Pal, Helena J. H.; Koning, Caro C. E.; Oldenburger, Foppe; Wilde, James C. H.; Taminiau, Jan A. J. M.; Caron, Huib N.; van Dalen, Elvira C.

2013-01-01

Childhood cancer survivors (CCS) are a growing group of young individuals with a high risk of morbidity and mortality. We evaluated the prevalence and risk factors of hepatic late adverse effects, defined as elevated liver enzymes, in a large cohort of CCS. The cohort consisted of all five-year CCS

Endocrinopathies in Survivors of Childhood Neoplasia

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NICOLE S BARNES

2014-09-01

Full Text Available Advancements in cancer treatments have increased the number of childhood cancer survivors. Endocrinopathies are common complications following cancer therapy and may occur decades later. The objective of the 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.

Acetaminophen-Induced Liver Injury Alters the Acyl Ethanolamine-Based Anti-Inflammatory Signaling System in Liver

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Patricia Rivera

2017-10-01

Full Text Available Protective mechanisms against drug-induced liver injury are actively being searched to identify new therapeutic targets. Among them, the anti-inflammatory N-acyl ethanolamide (NAE-peroxisome proliferators activated receptor alpha (PPARα system has gained much interest after the identification of its protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol (APAP, a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it is being used as a liver model. In the present study, we have analyzed the impact of APAP on the liver NAE-PPARα system. A dose-response (0.5–5–10–20 mM and time-course (2–6–24 h study in human HepG2 cells showed a biphasic response, with a decreased PPARα expression after 6-h APAP incubation followed by a generalized increase of NAE-PPARα system-related components (PPARα, NAPE-PLD, and FAAH, including the NAEs oleoyl ethanolamide (OEA and docosahexaenoyl ethanolamide, after a 24-h exposure to APAP. These results were partially confirmed in a time-course study of mice exposed to an acute dose of APAP (750 mg/kg. The gene expression levels of Pparα and Faah were decreased after 6 h of treatment and, after 24 h, the gene expression levels of Nape-pld and Faah, as well as the liver levels of OEA and palmitoyl ethanolamide, were increased. Repeated APAP administration (750 mg/kg/day up to 4 days also decreased the expression levels of PPARα and FAAH, and increased the liver levels of NAEs. A resting period of 15 days completely restored these impairments. Liver immunohistochemistry in a well-characterized human case of APAP hepatotoxicity confirmed PPARα and FAAH decrements. Histopathological and hepatic damage (Cyp2e1, Caspase3, αSma, Tnfα, and Mcp1-related alterations observed after repeated APAP administration were aggravated in the liver of Pparα-deficient mice. Our results demonstrate that the anti-inflammatory NAE-PPARα signaling system is implicated in liver

Role of liver progenitors in liver regeneration.

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Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A; Canbay, Ali

2015-02-01

During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs.

Childhood Origins of Young Adult Environmental Behavior.

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Evans, Gary W; Otto, Siegmar; Kaiser, Florian G

2018-05-01

Prospective, longitudinal analyses revealed that over a 12-year period from ages 6 to 18, individuals who grew up with mothers with more proenvironmental attitudes engaged in more proenvironmental behavior as young adults. A similar marginal association was uncovered between mothers' proenvironmental behaviors and the proenvironmental behavior of their young adult offspring. Maternal educational attainment, but not political ideology, was also associated with more proenvironmental behavior as children matured. Moreover, childhood time spent outdoors was positively associated with increased environmentally responsible behavior in young adulthood. Interestingly, one's own childhood proenvironmental behavior and attitude, at least as assessed at age 6, bear little on one's eventual proenvironmental behavior as a young adult. Finally, among this set of childhood factors, maternal education and childhood time spent outdoors were independent predictors of positive changes in environmental behavior from early childhood to young adulthood.

Patients with HBV-related acute-on-chronic liver failure have increased concentrations of extracellular histones aggravating cellular damage and systemic inflammation.

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Li, X; Gou, C; Yao, L; Lei, Z; Gu, T; Ren, F; Wen, T

2017-01-01

Acute-on-chronic liver failure (ACLF) is the most common type of liver failure and associated with grave consequences. Systemic inflammation has been linked to its pathogenesis and outcome, but the identifiable triggers are absent. Recently, extracellular histones, especially H4, have been recognized as important mediators of cell damage in various inflammatory conditions. This study aimed to investigate whether extracellular histones have clinical implications in patients with hepatitis B virus (HBV)-related ACLF. One hundred and twelve patients with HBV-related ACLF, 90 patients with chronic hepatitis B, 88 patients with HBV-related liver cirrhosis and 40 healthy volunteers were entered into this study. Plasma histone H4 levels, cytokine profile and clinical data were obtained. Besides, patient's sera were incubated overnight with human L02 hepatocytes or monocytic U937 cells in the presence or absence of antihistone H4 antibody, and cellular damage and cytokine production were evaluated. We found that plasma histone H4 levels were greatly increased in patients with ACLF as compared with chronic hepatitis B, liver cirrhosis and healthy control subjects and were significantly associated with disease severity, systemic inflammation and outcome. Notably, ACLF patients' sera incubation decreased cultured L02 cell integrity and induced profound cytokine production in the supernatant of U937 cells. Antihistone H4 antibody treatment abrogated these adverse effects, thus confirming a cause-effect relationship between extracellular histones and organ injury/dysfunction. The data support the hypothesis that the increased extracellular histone levels in ACLF patients may aggravate disease severity by inducing cellular injury and systemic inflammation. Histone-targeted therapies may have potentially interventional value in clinical practice. © 2016 John Wiley & Sons Ltd.

Liver Transplantation: Evolving Patient Selection Criteria

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Andy S Yu

2001-01-01

Full Text Available The widespread recognition of the success of liver transplantation as a treatment for most types of acute and chronic liver failure has led to increased referrals for transplantation in the setting of a relatively fixed supply of cadaver donor organs. These events have led to a marked lengthening of the waiting time for liver transplantation, resulting in increased deaths of those on the waiting list and sicker patients undergoing transplantation. Nearly 5000 liver transplantations were performed in the United States in 2000, while the waiting list grew to over 17,000 patients. The mounting disparity between the number of liver transplant candidates and the limited supply of donor organs has led to reassessment of the selection and listing criteria for liver transplantation, as well as revision of organ allocation and distribution policies for cadaver livers. The development of minimal listing criteria for patients with chronic liver disease based on a specific definition for decompensation of cirrhosis has facilitated the more uniform listing of patients at individual centres across the United States. The United Network for Organ Sharing, under pressure from transplant professionals, patient advocacy groups and the federal government, has continuously revised allocation and distribution policies based on the ethical principles of justice for the individual patient versus optimal utility of the limited organ supply available annually. Beginning in 2002, it is likely that the Model for End-stage Liver Disease (MELD score will be implemented to determine disease severity and direct donor organs to the sickest patients rather than to those with the longest waiting times.

Liver Development, Regeneration, and Carcinogenesis

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Janet W. C. Kung

2010-01-01

Full Text Available The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats

NARCIS (Netherlands)

Díaz-Rúa, Rubén; Keijer, Jaap; Palou, Andreu; Schothorst, van Evert M.; Oliver, Paula

2017-01-01

Intake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular

Attachment in Middle Childhood: Progress and Prospects

Science.gov (United States)

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…

Treatment of Childhood Obesity: A Systematic Review

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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…

Antifibrotic and molecular aspects of rifaximin in alcoholic liver disease

DEFF Research Database (Denmark)

Madsen, Bjørn Stæhr; Trebicka, Jonel; Thiele, Maja

2018-01-01

Background: Alcoholic liver disease is the leading cause of cirrhosis worldwide. Due to an increase in alcohol overuse, alcoholic liver disease has become an increased burden on health care systems. Abstinence from alcohol remains the cornerstone of alcoholic liver disease treatment; however......, this approach is hampered by frequent relapse and lack of specific therapy for treating advanced cases of liver disease. In the present study, we hypothesized that gut microbiota drive the development of liver fibrosis and that modulation of gut microbiota with the gut-selective, nonabsorbable antibiotic...... promoter of alcoholic liver disease, current results may open new therapeutic avenues and revolutionize the current understanding of chronic liver diseases....

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

International Nuclear Information System (INIS)

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

1983-01-01

The blood-to-brain transfer of [ 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 [ 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 [ 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

Nutritional Therapy in Liver Transplantation

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Ahmed Hammad

2017-10-01

Full Text Available Protein-energy malnourishment is commonly encountered in patients with end-stage liver disease who undergo liver transplantation. Malnutrition may further increase morbidity, mortality and costs in the post-transplantation setting. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognized. The metabolic abnormalities induced by liver failure render the conventional assessment of nutritional status to be challenging. Preoperative loss of skeletal muscle mass, namely, sarcopenia, has a significant detrimental impact on post-transplant outcomes. It is essential to provide sufficient nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the needed energy intake. Herein, the latest currently employed perioperative nutritional interventions in liver transplant recipients are thoroughly illustrated including synbiotics, micronutrients, branched-chain amino acid supplementation, immunonutrition formulas, fluid and electrolyte balance, the offering of nocturnal meals, dietary counselling, exercise and rehabilitation.

Expression analysis of CD63 in salivary neutrophils and the increased level of Streptococcus mutans in severe early childhood caries

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Muhammad Luthfi

2015-06-01

Full Text Available Background: Severe early childhood caries (S-ECC and decay exfoliation filling teeth (def-t >6 is a destructive disease that afflicts teeth, including maxillary anterior teeth. In Indonesia, the prevalence of this disease is still high, for instance in Semarang 2007, the rate reached 90.5% in urban areas and 95.9% in rural areas for early childhood caries which is caused by Streptococcus mutans (S. mutans. Neutrophils are effector cells of innate immunity which become the main component of the very first line of defense against microbes. Purpose: This study analyzed the effect caused by the change of CD63 expression on the surface of salivary neutrophils and the increased level of S. mutans in S-ECC. Method: This study employs observational analytic and cross sectional approach by using T test analysis technique for forty cases of early childhood that had been divided into two groups, first group of twenty children positively diagnosed as S-ECC and second group of twenty children negatively diagnosed as the control group. The sample’s result of gargling with 1.5% NaCl was used for neutrophils isolation and analysis function of salivary neutrophils phagocytosis by using flow cytometry test, while the sample of saliva was used to isolate S. mutans and calculate the level of S. mutans. Result: The expression of CD63+ salivary neutrophils in S-ECC was lower (2.32% ± 0.57 than in caries-free (2.67% ± 0.46, while the level of S. mutans showed that the level was not higher than in S-ECC (9.78 ± 2.22x105 CFU/ml compared to in caries-free (5.13 ± 1.86x105 CFU/ml. Conclusion: The low expression of CD63 in salivary neutrophils can lead to the increased level of S. mutans in S-ECC.

Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease.

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Davide Povero

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy.Choline Deficient L-Amino Acid (CDAA and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens.We observed statistically significant differences in the level of extracellular vesicles (EVs in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05, fibrosis (r2 = 0.66, p<0.05 and pathological angiogenesis (r2 = 0.71, p<0.05. Extensive characterization of blood EVs identified both microparticles (MPs and exosomes (EXO present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192--two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver.These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.

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

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

2014-01-01

Soluble CD36 (sCD36) clusters with insulin resistance, but no evidence exists on its relationship with hepatic fat content. We determined sCD36 to assess its link to steatosis in nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) patients. Two hundred and twenty-seven NAFLD, eighty-seven CHC, and eighty-five patients with histologically normal liver (NL) were studied. Steatosis was graded by Kleiner's histological scoring system. Serum sCD36 and hepatic CD36 expression was assessed by immunoassay and immunohistochemistry, respectively. In NAFLD, serum sCD36 levels were significantly higher in simple steatosis than in NL (361.4 ± 286.4 vs. 173.9 ± 137.4 pg/mL, respectively; P steatosis (387.2 ± 283.6 pg/mL; P = 0.173). A progressive increase in serum sCD36 values was found in NAFLD depending on the histological grade of steatosis (P steatosis in NAFLD when adjusted by demographic and anthropometric features [odds ratio (OR), 1.001; 95% confidence interval (CI), 1.000 to 1.002; P = 0.021] and by metabolic variables (OR, 1.002; 95% CI, 1.000 to 1.003; P = 0.001). Interestingly, a significant correlation was observed between hepatic CD36 and serum sCD36 (ρ = 0.499, P steatosis in NAFLD. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

General Overview on Childhood Obesity

OpenAIRE

Sevil İnal; Nejla Canbulat

2013-01-01

Until recently, it has not been put much emphasis on obesity in children and the view of “obese child is healthy” is widely accepted by families. However, understanding that a close relation exists between obesity prevalence and childhood obesity, which increased in recent years both across the world and in our country, and many diseases such as hypertension, diabetes, cardiovascular diseases changed the opinion of both of health care professionals and the society about childhood obesity in T...

Outcomes of Childhood Asthma and Wheezy Bronchitis. A 50-Year Cohort Study.

Science.gov (United States)

Tagiyeva, Nara; Devereux, Graham; Fielding, Shona; Turner, Stephen; Douglas, Graham

2016-01-01

Cohort studies suggest that airflow obstruction is established early in life, manifests as childhood asthma and wheezy bronchitis, and continues into early adulthood. Although an association between childhood asthma and chronic obstructive pulmonary disease (COPD) in later life has been demonstrated, it is unclear if childhood wheezy bronchitis is associated with COPD. To investigate whether childhood wheezy bronchitis increases the risk of COPD in the seventh decade. A cohort of children recruited in 1964 at age 10 to 15 years, which was followed up in 1989, 1995, and 2001, was followed up again in 2014 when at age 60 to 65 years. Discrete time-to-event and linear mixed effects models were used. FEV1 and FVC were measured. COPD was defined as post-bronchodilator FEV1/FVC Childhood wheezing phenotype was related to 1989, 1995, 2001, and 2014 spirometry data. Three hundred thirty subjects, mean age 61 years, were followed up: 38 with childhood asthma; 53 with childhood wheezy bronchitis; and 239 control subjects (of whom 57 developed adulthood-onset wheeze between ages 16 and 46 yr). In adjusted multivariate analyses, childhood asthma was associated with an increased risk of COPD (odds ratio, 6.37; 95% confidence interval, 3.73-10.94), as was childhood wheezy bronchitis (odd ratio 1.81; 95% confidence interval, 1.12-2.91). The COPD risk increased with childhood asthma, and wheezy bronchitis was associated with reduced FEV1 that was evident by the fifth decade and not an accelerated rate of FEV1 decline. In contrast, adulthood-onset wheeze was associated with accelerated FEV1 decline. Childhood wheezy bronchitis and asthma are associated with an increased risk of COPD and reduced ventilatory function.

[Preoperative imaging/operation planning for liver surgery].

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Schoening, W N; Denecke, T; Neumann, U P

2015-12-01

The currently established standard for planning liver surgery is multistage contrast media-enhanced multidetector computed tomography (CM-CT), which as a rule enables an appropriate resection planning, e.g. a precise identification and localization of primary and secondary liver tumors as well as the anatomical relation to extrahepatic and/or intrahepatic vascular and biliary structures. Furthermore, CM-CT enables the measurement of tumor volume, total liver volume and residual liver volume after resection. Under the condition of normal liver function a residual liver volume of 25 % is nowadays considered sufficient and safe. Recent studies in patients with liver metastases of colorectal cancer showed a clear staging advantage of contrast media-enhanced magnetic resonance imaging (CM-MRI) versus CM-CT. In addition, most recent data showed that the use of liver-specific MRI contrast media further increases the sensitivity and specificity of detection of liver metastases. This imaging technology seems to lead closer to the ideal "one stop shopping" diagnostic tool in preoperative planning of liver resection.

Does acid-base equilibrium correlate with remnant liver volume during stepwise liver resection?

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Golriz, Mohammad; Abbasi, Sepehr; Fathi, Parham; Majlesara, Ali; Brenner, Thorsten; Mehrabi, Arianeb

2017-10-01

Small for size and flow syndrome (SFSF) is one of the most challenging complications following extended hepatectomy (EH). After EH, hepatic artery flow decreases and portal vein flow increases per 100 g of remnant liver volume (RLV). This causes hypoxia followed by metabolic acidosis. A correlation between acidosis and posthepatectomy liver failure has been postulated but not studied systematically in a large animal model or clinical setting. In our study, we performed stepwise liver resections on nine pigs to defined SFSF limits as follows: step 1: segment II/III resection, step 2: segment IV resection, step 3: segment V/VIII resection (RLV: 75, 50, and 25%, respectively). Blood gas values were measured before and after each step using four catheters inserted into the carotid artery, internal jugular vein, hepatic artery, and portal vein. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. EH correlated with reduced BE in the hepatic artery. Pco 2 values increased after 75% resection in the jugular vein. In contrast, arterial Po 2 increased after every resection, whereas the venous Po 2 decreased slightly. There were differences in venous [Formula: see text], BE in the hepatic artery, and Pco 2 in the jugular vein after 75% liver resection. Because 75% resection is the limit for SFSF, these noninvasive blood evaluations may be used to predict SFSF. Further studies with long-term follow-up are required to validate this correlation. NEW & NOTEWORTHY This is the first study to evaluate acid-base parameters in major central and hepatic vessels during stepwise liver resection. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. Extended hepatectomy correlated with reduced BE in the hepatic artery. Because 75% resection is the limit for small for size and flow

Montelukast induced acute hepatocellular liver injury

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Harugeri A

2009-01-01

Full Text Available A 46-year-old male with uncontrolled asthma on inhaled albuterol and formoterol with budesonide was commenced on montelukast. He developed abdominal pain and jaundice 48 days after initiating montelukast therapy. His liver tests showed an increase in serum total bilirubin, conjugated bilirubin, aspartate aminotranferase, alanine aminotranferase, and alkaline phosphatase. The patient was evaluated for possible non-drug related liver injury. Montelukast was discontinued suspecting montelukast induced hepatocellular liver injury. Liver tests began to improve and returned to normal 55 days after drug cessation. Causality of this adverse drug reaction by the Council for International Organizations of Medical Sciences or Roussel Uclaf Causality Assessment Method (CIOMS or RUCAM and Naranjo′s algorithm was ′probable′. Liver tests should be monitored in patients receiving montelukast and any early signs of liver injury should be investigated with a high index of suspicion for drug induced liver injury.

An increase in circulating B cell-activating factor in childhood-onset ocular myasthenia gravis.

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Motobayashi, Mitsuo; Inaba, Yuji; Nishimura, Takafumi; Kobayashi, Norimoto; Nakazawa, Yozo; Koike, Kenichi

2015-04-01

Myasthenia gravis is a B cell-mediated autoimmune disorder. The pathophysiology of childhood-onset ocular myasthenia gravis remains unclear. We investigated serum B cell-activating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. Blood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B cell-activating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-γ; tumor necrosis factor-α) as well as the percentages of peripheral blood CD4+, CD8+, and CD19+ cells. Serum B cell-activating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B cell-activating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B cell-activating factor concentrations did not correlate with the percentages of CD4+, CD8+, and CD19+ cells or the CD4+/CD8+ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. Circulating B cell-activating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis. Copyright © 2015 Elsevier Inc. All rights reserved.

INDIAN CHILDHOOD AND OTHER CHILDHOODS

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Alceu Zoia

2010-12-01

Full Text Available This article aims to show how children of the Indian community Terena, from North Mato Grosso, live, how they are educated, and what are the conceptions of childhood among the members of this community. Taking childhood in various contexts, we seek to analyze how this education process has been carried out.

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

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J. Schmitz

2016-05-01

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 inflammation and insulin resistance in mice as well as in a significant subpopulation of obese patients.

Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver

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Liu, Jinyao

2014-01-01

Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-α activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-α overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-α expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-α overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-α inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease. PMID:25356030

Childhood obesity and type 2 diabetes in India.

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Praveen, Pradeep A; Tandon, Nikhil

2016-04-01

India is witnessing an increase in the burden of childhood obesity, especially among the upper socioeconomic strata and in urban areas. Emerging literature suggests a link between childhood obesity and the diabetes epidemic in India. Asian-Indian children and adolescents are increasingly susceptible to a high percentage of body fat and abdominal adiposity. Further, they are exposed to an obesogenic environment, created by rapid urbanization and nutrition transition in India. Obese children have a higher risk of developing abnormalities that are recognized as precursors to diabetes, such as subclinical inflammation, insulin resistance and metabolic syndrome, which often track to adulthood. A review of the literature suggests the need for more longitudinal studies to improve understanding of the long-term consequences of childhood obesity in India. A life-course approach with a combination of population- and risk-based strategies is warranted, to prevent childhood obesity and curtail its consequences in adulthood.

Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors

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Jansen, P.L.M.; Chamuleau, R.A.F.; Leeuwen, D.J. van; Schippor, H.G.; Busemann-Sokole, E.; Heyde, M.N. van der

1990-01-01

Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single photon computed tomography (SPECT), using 99m Tc-colloid as tracer. The method was assessed in 11 patients by comparing the pre- and post-operative volume measurement with the volume of the resected liver mass. Liver function was determined by measuring the galactose elimination capacity and the caffeine clearance. After a postoperative follow-up period of 50 days, the liver had regenerated maximally to a volume of 75 ± 2% of the preoperative liver mass. Maximal restoration of liver function was achieved 120 days after operation and amounted to 75 ± 10% for the caffeine clearance and to 100 ± 25% for the galactose elimination capacity. This study shows that SPECT is a useful method for assessing liver regeneration in patients after partial hepatectomy. The study furthermore shows that caffeine clearance correlates well with total liver volume, whereas the galactose elimination capacity overestimates total liver volume after partial hepatectomy. 22 refs

Effects of Fatty Liver Induced by Excess Orotic Acid on B-Group Vitamin Concentrations of Liver, Blood, and Urine in Rats.

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Shibata, Katsumi; Morita, Nobuya; Kawamura, Tomoyo; Tsuji, Ai; Fukuwatari, Tsutomu

2015-01-01

Fatty liver is caused when rats are given orotic acid of the pyrimidine base in large quantities. The lack of B-group vitamins suppresses the biosynthesis of fatty acids. We investigated how orotic acid-induced fatty liver affects the concentrations of liver, blood, and urine B-group vitamins in rats. The vitamin B6 and B12 concentrations of liver, blood, and urine were not affected by orotic acid-induced fatty liver. Vitamin B2 was measured only in the urine, but was unchanged. The liver, blood, and urine concentrations of niacin and its metabolites fell dramatically. Niacin and its metabolites in the liver, blood, and urine were affected as expected. Although the concentrations of vitamin B1, pantothenic acid, folate, and biotin in liver and blood were decreased by orotic acid-induced fatty liver, these urinary excretion amounts showed a specific pattern toward increase. Generally, as for the typical urinary excretion of B-group vitamins, these are excreted when the body is saturated. However, the ability to sustain vitamin B1, pantothenic acid, folate, and biotin decreased in fatty liver, which is hypothesized as a specific phenomenon. This metabolic response might occur to prevent an abnormally increased biosynthesis of fatty acids by orotic acid.

[Eating behavior and childhood obesity: family influences].

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Domínguez-Vásquez, P; Olivares, S; Santos, J L

2008-09-01

Eating behavior involves all actions that define the relation between human beings and food. It is accepted that feeding habits are acquired through eating experiences and practices learned from the familiar and social context in early childhood. Besides the role of the social context, it is also assumed that familiar factors, both common family environment and genetic inheritance, have an important influence on food intake and eating behavior linked with childhood obesity. Research on food intake and childhood obesity has been traditionally focused on the amount and type of foods in the usual diet. However, it is an increasing interest to understand the link between eating behavior and obesity using questionnaires. There are several psychometric tools that have been developed specifically to deal with human eating behavior. This review summarizes the family influences, both genetic and non-genetic, on childhood feeding behavior and their relation to childhood obesity.

Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis.

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Koo, Seung-Hoi

2013-09-01

Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.

The regulation of cytoskeletal and liver-specific gene expression during liver regeneration and primary hepatocyte culture

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Robinson, G.S.

1989-01-01

The focus of this dissertation is to determine what role(s) the extracellular matrix and expression of certain cytoskeletal genes play in the regulation of hepatocyte growth and the maintenance of a differential state. The expression of several cytoskeletal and liver-specific genes was examined during liver regeneration and in hepatocyte cultures maintained in a hormonally-defined, serum-free medium and plated on two different matrices: rat tail collagen and the EHS matrix. During liver regeneration and in hepatocytes cultured on rat tail collagen, there was a dramatic increase in tubulin mRNA levels coincident with but not linked to DNA synthesis. The message levels for other cytoskeletal genes similarly increased, while a decrease was observed in the mRNA levels of the liver-specific genes, serum albumin and alpha 1 inhibitor III. Hepatocytes cultured on the EHS matrix resulted in the maintenance of low levels of cytoskeletal gene expression and high levels of liver-specific gene expression, similar to that observed in the normal liver. Results from subcellar fractionation and two-dimensional gel electrophoresis of 35 S-labelled proteins paralleled the results seen at the mRNA level. Preliminary work suggests that microtubule organization may play a role in the expression of the liver-specific genes which encode secreted proteins. These studies, which compare hepatocytes cultured on collagen or the EHS matrix gel, reveal that both cell-cell and cell-matrix interactions play a major role in the maintenance of the differential phenotype in hepatocytes

Prevalence and determinants of childhood mortality in Nigeria

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Sanni Yaya

2017-05-01

Full Text Available Abstract Background Childhood mortality has remained a major challenge to public health amongst families in Nigeria and other developing countries. The menace of incessant childhood mortality has been a major concern and this calls for studies to generate new scientific evidence to determine its prevalence and explore predisposing factors associated with it in Nigeria. Method Data was obtained from Nigeria DHS, 2013. The study outcome variable was the total number of children lost by male partners and female partners respectively who were married. The difference between the numbers of child births and the number of living children was used to determine the number of children lost. Study variables were obtained for 8658 couples captured in the data set. Descriptive statistics were computed to examine the presence of over-dispersion and zero occurrences. Data were analysed using STATA Software version 12.0. Zero-inflated negative binomial (ZINB regression analysis was carried out to determine the factors associated with childhood mortality. Results of ZINB were reported in terms of IRR and 95% confidence interval (CI. Results The age (mean ± std. of male and female participants were 36.88 ± 7.37 and 28.59 ± 7.30 respectively. The data showed that 30.8% women reported loss of children and 37.3% men reported the same problem. The study revealed age (years, region, residence, education, wealth index, age at first birth and religion of father and mother as factors associated with childhood mortality. In terms of education, secondary and tertiary educated fathers exhibited 3.8% and 12.1% lower risk of childhood mortality respectively than non-educated fathers. The results showed that the risk of childhood mortality are 26.7%, 39.7 and 45.9% lower among the mothers having primary, secondary and tertiary education respectively than those with no formal education. The mothers living in rural areas experienced 28.3% increase in childhood mortality

Prevalence and determinants of childhood mortality in Nigeria.

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Yaya, Sanni; Ekholuenetale, Michael; Tudeme, Godson; Vaibhav, Shah; Bishwajit, Ghose; Kadio, Bernard

2017-05-22

Childhood mortality has remained a major challenge to public health amongst families in Nigeria and other developing countries. The menace of incessant childhood mortality has been a major concern and this calls for studies to generate new scientific evidence to determine its prevalence and explore predisposing factors associated with it in Nigeria. Data was obtained from Nigeria DHS, 2013. The study outcome variable was the total number of children lost by male partners and female partners respectively who were married. The difference between the numbers of child births and the number of living children was used to determine the number of children lost. Study variables were obtained for 8658 couples captured in the data set. Descriptive statistics were computed to examine the presence of over-dispersion and zero occurrences. Data were analysed using STATA Software version 12.0. Zero-inflated negative binomial (ZINB) regression analysis was carried out to determine the factors associated with childhood mortality. Results of ZINB were reported in terms of IRR and 95% confidence interval (CI). The age (mean ± std.) of male and female participants were 36.88 ± 7.37 and 28.59 ± 7.30 respectively. The data showed that 30.8% women reported loss of children and 37.3% men reported the same problem. The study revealed age (years), region, residence, education, wealth index, age at first birth and religion of father and mother as factors associated with childhood mortality. In terms of education, secondary and tertiary educated fathers exhibited 3.8% and 12.1% lower risk of childhood mortality respectively than non-educated fathers. The results showed that the risk of childhood mortality are 26.7%, 39.7 and 45.9% lower among the mothers having primary, secondary and tertiary education respectively than those with no formal education. The mothers living in rural areas experienced 28.3% increase in childhood mortality than those in urban areas, while the fathers in

Neurofunctional Abnormalities during Sustained Attention in Severe Childhood Abuse

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Mehta, Mitul A.; Simmons, Andrew; Mirza, Kah; Rubia, Katya

2016-01-01

Childhood maltreatment is associated with adverse affective and cognitive consequences including impaired emotion processing, inhibition and attention. However, the majority of functional magnetic resonance imaging (fMRI) studies in childhood maltreatment have examined emotion processing, while very few studies have tested the neurofunctional substrates of cognitive functions and none of attention. This study investigated the association between severe childhood abuse and fMRI brain activation during a parametric sustained attention task with a progressively increasing load of sustained attention in 21 medication-naïve, drug-free young people with a history of childhood abuse controlling for psychiatric comorbidities by including 19 psychiatric controls matched for psychiatric diagnoses, and 27 healthy controls. Behaviorally, the participants exposed to childhood abuse showed increased omission errors in the task which correlated positively trend-wise with the duration of their abuse. Neurofunctionally, the participants with a history of childhood abuse, but not the psychiatric controls, displayed significantly reduced activation relative to the healthy controls during the most challenging attention condition only in typical attention regions including left inferior and dorsolateral prefrontal cortex, insula and temporal areas. We therefore show for the first time that severe childhood abuse is associated with neurofunctional abnormalities in key ventral frontal-temporal sustained attention regions. The findings represent a first step towards the delineation of abuse-related neurofunctional abnormalities in sustained attention, which may help in the development of effective treatments for victims of childhood abuse. PMID:27832090

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

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Jereb Sara

2016-06-01

Full Text Available 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.

Diagnosis and treatment procedure for intractable liver ascites

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FAN Zhidong

2015-03-01

Full Text Available Ascites is a common complication of liver cirrhosis. Liver ascites may occur repeatedly, which increases the therapeutic difficulty. This paper reviews the definition of intractable liver ascites, general treatment measures, and current treatment of common complications such as spontaneous bacterial peritonitis and hepatorenal syndrome, as well as the advances in conventional, unconventional, and surgical treatment of intractable liver ascites. It is pointed out that abdominocentesis for excessive drainage and active preparation for liver transplantation are the preferred approach to the treatment of intractable liver ascites.

Multicultural Teaching Competence of Korean Early Childhood Educators

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Park, Sungok R.

2016-01-01

Discourse among early childhood education researchers increasingly emphasizes the need for teachers to better understand and support diversity in their classrooms. As part of a larger mixed-method study, this qualitative research illuminates Korean early childhood educators' multicultural teaching competence. While Korean classrooms are in…

Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

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Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen

2012-01-01

Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664

Increased Level of Interleukin 6 Associates With Increased 90-Day and 1-Year Mortality in Patients With End-Stage Liver Disease.

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Remmler, Johannes; Schneider, Christoph; Treuner-Kaueroff, Theresa; Bartels, Michael; Seehofer, Daniel; Scholz, Markus; Berg, Thomas; Kaiser, Thorsten

2018-05-01

Organ allocation for liver transplantation is based on prognosis, using the model for end-stage liver disease (MELD) or MELD including serum sodium (MELD-Na) score. These scores do not consider systemic inflammation and septic complications. Blood level of C-reactive protein (CRP), in addition to the MELD score, associates with mortality in patients with end-stage liver disease, whereas levels of interleukin 6 (IL6) have not been systematically studied. We performed a retrospective observational cohort study of 474 patients with end-stage liver disease (63.5% male; median age, 56.9 years), evaluated for liver transplantation in Germany, with at least 1 year of follow up. Data were collected on blood levels of CRP, IL6, and white blood cell count (WBC). Findings were analyzed in relation to mortality and compared with patients' MELD scores and MELD-Na scores. For survival analysis, the cohort was divided into quartiles of IL6, CRP, and WBC levels, as well as MELD scores. Log-rank test and the Cox proportional hazards regression model were used to compare the groups, and area under the receiver operating characteristic (AUROC) values were calculated. Blood levels of IL6 and MELD scores associated with mortality: none of the patients with levels of IL6 below the first quartile (below 5.3 pg/mL) died within 1 year. In contrast, 67.7% of the patients in the highest quartile of IL6 level (37.0 pg/mL or more) died within 1 year. MELD score also correlated with mortality: among patients with MELD scores below 8.7, 0.9% died within 1 year, whereas in patients with MELD scores of 18.0 or more, 67.4% died within 1 year. The predictive value of level of IL6 (AUROC, 0.940) was higher than level of CRP (AUROC, 0.866) (P = .009) or WBC (AUROC, 0.773) (P Level of IL6 associated with 1-year mortality (AUROC, 0.916) to a greater extent than liver synthesis or detoxification markers international normalized ratio (AUROC, 0.839) (P = .007) or bilirubin (AUROC 0.846) (P = .007

Monocytes with angiogenic potential are selectively induced by liver resection and accumulate near the site of liver regeneration.

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Schauer, Dominic; Starlinger, Patrick; Zajc, Philipp; Alidzanovic, Lejla; Maier, Thomas; Buchberger, Elisabeth; Pop, Lorand; Gruenberger, Birgit; Gruenberger, Thomas; Brostjan, Christine

2014-10-30

Monocytes reportedly contribute to liver regeneration. Three subsets have been identified to date: classical, intermediate, non-classical monocytes. The intermediate population and a subtype expressing TIE2 (TEMs) were suggested to promote angiogenesis. In a clinical setting, we investigated which monocyte subsets are regulated after liver resection and correlate with postoperative liver function. In 38 patients monocyte subsets were evaluated in blood and subhepatic wound fluid by flow cytometry before and 1-3 days after resection of colorectal liver metastases. The monocyte-regulating cytokines macrophage colony stimulating factor (M-CSF), transforming growth factor beta 1 (TGFβ1), and angiopoietin 2 (ANG-2) were measured in patient plasma by ELISA. C-reactive protein (CRP) and liver function parameters were retrieved from routine hospital analyses. On post-operative day (POD) 1 blood monocytes shifted to significantly elevated levels of intermediate monocytes. In wound fluid, a delayed surge in intermediate monocytes was detected by POD 3. Furthermore, TEMs were highly enriched in wound fluid as compared to circulation. CRP and M-CSF levels were substantially increased in patient blood after surgery and correlated significantly with the frequency of intermediate monocytes. In addition, liver function parameters showed a significant association with intermediate monocyte levels on POD 3. The reportedly pro-angiogenic subsets of monocytes are selectively increased upon liver resection and accumulate next to the site of liver regeneration. As previously proposed by in vitro experiments, the release of CRP and M-CSF may trigger the induction of intermediate monocytes. The correlation with liver parameters points to a functional involvement of these monocyte populations in liver regeneration which warrants further investigation.

Advances in sepsis-associated liver dysfunction

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Dawei Wang

2014-07-01

Full Text Available Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS, and subsequent activation of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs, hepatocytes and liver sinusoidal endothelial cells (LSECs. In addition, activated neutrophils, which are also recruited to the liver and produce potentially destructive enzymes and oxygen-free radicals, may further enhance acute liver injury. The clinical manifestations of sepsis-associated liver dysfunction can roughly be divided into two categories: Hypoxic hepatitis and jaundice. The latter is much more frequent in the context of sepsis. Hepatic failure is traditionally considered as a late manifestation of sepsis-induced multiple organ dysfunction syndrome. To date, no specific therapeutics for sepsis-associated liver dysfunction are available. Treatment measure is mainly focused on eradication of the underlying infection and management for severe sepsis. A better understanding of the pathophysiology of liver response in sepsis may lead to further increase in survival rates.

Childhood adversity, recent life stressors and suicidal behavior in Chinese college students.

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Zhiqi You

Full Text Available BACKGROUND: Although the independent effects of childhood adversities and of recent negative events on suicidality have been well-documented, the combinative role of childhood and recent adversities on risk for suicidality is still underexplored, especially in the context of Chinese culture and in consideration of specific types of negative events. METHOD: 5989 students, randomly sampled from six universities in central China, completed the online survey for this study. Suicidal behavior, life adversity during childhood and stressful events in recent school life were assessed with designed questionnaires. RESULTS: Students experiencing recent stressful life events more often reported an experience of life adversity during childhood. While recent stressful life events and childhood life adversity both were associated with an increased risk for suicidal behavior, the two exposures presented conjunctively and acted interactively to increase the risk. There was noticeable variation of effects associated with specific childhood life adversities, and sexual abuse, poor parental relationship, divorce of parents and loss of a parent were among the adversities associated with the highest increased risk. Recent conflicts with classmates, poor school performance and rupture of romantic relationships were the recent school life stressors associated with the highest increased risk. CONCLUSIONS: Childhood adversity and recent school life stressors had a combinative role in predicting suicidality of young people studying in Chinese colleges. Unhappy family life during childhood and recent interpersonal conflicts in school were the most important predictors of suicidality in this population.

Childhood adversity, recent life stressors and suicidal behavior in Chinese college students.

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You, Zhiqi; Chen, Mingxi; Yang, Sen; Zhou, Zongkui; Qin, Ping

2014-01-01

Although the independent effects of childhood adversities and of recent negative events on suicidality have been well-documented, the combinative role of childhood and recent adversities on risk for suicidality is still underexplored, especially in the context of Chinese culture and in consideration of specific types of negative events. 5989 students, randomly sampled from six universities in central China, completed the online survey for this study. Suicidal behavior, life adversity during childhood and stressful events in recent school life were assessed with designed questionnaires. Students experiencing recent stressful life events more often reported an experience of life adversity during childhood. While recent stressful life events and childhood life adversity both were associated with an increased risk for suicidal behavior, the two exposures presented conjunctively and acted interactively to increase the risk. There was noticeable variation of effects associated with specific childhood life adversities, and sexual abuse, poor parental relationship, divorce of parents and loss of a parent were among the adversities associated with the highest increased risk. Recent conflicts with classmates, poor school performance and rupture of romantic relationships were the recent school life stressors associated with the highest increased risk. Childhood adversity and recent school life stressors had a combinative role in predicting suicidality of young people studying in Chinese colleges. Unhappy family life during childhood and recent interpersonal conflicts in school were the most important predictors of suicidality in this population.

Childhood Adversity, Recent Life Stressors and Suicidal Behavior in Chinese College Students

Science.gov (United States)

You, Zhiqi; Chen, Mingxi; Yang, Sen; Zhou, Zongkui; Qin, Ping

2014-01-01

Background Although the independent effects of childhood adversities and of recent negative events on suicidality have been well-documented, the combinative role of childhood and recent adversities on risk for suicidality is still underexplored, especially in the context of Chinese culture and in consideration of specific types of negative events. Method 5989 students, randomly sampled from six universities in central China, completed the online survey for this study. Suicidal behavior, life adversity during childhood and stressful events in recent school life were assessed with designed questionnaires. Results Students experiencing recent stressful life events more often reported an experience of life adversity during childhood. While recent stressful life events and childhood life adversity both were associated with an increased risk for suicidal behavior, the two exposures presented conjunctively and acted interactively to increase the risk. There was noticeable variation of effects associated with specific childhood life adversities, and sexual abuse, poor parental relationship, divorce of parents and loss of a parent were among the adversities associated with the highest increased risk. Recent conflicts with classmates, poor school performance and rupture of romantic relationships were the recent school life stressors associated with the highest increased risk. Conclusions Childhood adversity and recent school life stressors had a combinative role in predicting suicidality of young people studying in Chinese colleges. Unhappy family life during childhood and recent interpersonal conflicts in school were the most important predictors of suicidality in this population. PMID:24681891

Liver Transplant

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... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Adversity in childhood linked to elevated striatal dopamine function in adulthood

OpenAIRE

Egerton, A.; Valmaggia, L. R.; Howes, O. D.; Day, F.; Chaddock, C. A.; Allen, P.; Winton-Brown, T. T.; Bloomfield, M. A. P.; Bhattacharyya, S.; Chilcott, J.; Lappin, J. M.; Murray, R. M.; McGuire, P.

2016-01-01

Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and he...

Changes in lipidemia during chronic care treatment of childhood obesity

DEFF Research Database (Denmark)

Nielsen, Tenna Ruest Haarmark; Gamborg, Michael; Fonvig, Cilius Esmann

2012-01-01

Childhood obesity and related co-morbidities are increasing. This intervention study assessed the associations between weight changes and lipidemia in obese children and adolescents.......Childhood obesity and related co-morbidities are increasing. This intervention study assessed the associations between weight changes and lipidemia in obese children and adolescents....

Liver cell-targeted delivery of therapeutic molecules.

Science.gov (United States)

Kang, Jeong-Hun; Toita, Riki; Murata, Masaharu

2016-01-01

The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

Human immunodeficiency virus infection and the liver.

Science.gov (United States)

Crane, Megan; Iser, David; Lewin, Sharon R

2012-03-27

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.

Foetal exposure to maternal stressful events increases the risk of having asthma and atopic diseases in childhood.

Science.gov (United States)

de Marco, Roberto; Pesce, Giancarlo; Girardi, Paolo; Marchetti, Pierpaolo; Rava, Marta; Ricci, Paolo; Marcon, Alessandro

2012-12-01

The natural history of asthma and atopic diseases begins in utero. Studies investigating the influence of foetal exposure to maternal stressful life events during pregnancy (SLEP) on asthma and atopic diseases are lacking. To test whether the children of mothers who had experienced SLEP are at an increased risk for asthma, atopic eczema and allergic rhinitis. The association between maternal SLEP (at least one among: divorce, mourning or loss of the job) and the occurrence of asthma and atopic diseases in childhood was studied in a population (n = 3854) of children, aged 3-14 yrs, living in Northern Italy. The parents filled in a standardized questionnaire about the children's health and the events occurred to their mothers during pregnancy. Three hundred and thirty-three (9%) of the mothers experienced SLEP. Their children had a statistically significantly higher lifetime prevalence of wheezing (31.6% vs. 23.1%), asthma (8.9% vs. 5.6%), allergic rhinitis (10.9% vs. 7.3%) and atopic eczema (29.7% vs. 21.1%) than those of mothers without SLEP. After adjusting for potential confounders, the foetal exposure to SLEP was positively associated with wheezing (OR: 1.41, 95% CI: 1.03-1.94), asthma (OR: 1.71, 95% CI: 1.02-2.89), allergic rhinitis (OR: 1.75, 95% CI: 1.08-2.84) and atopic eczema (OR: 1.53, 95% CI: 1.11-2.10). The children of mothers who had experienced SLEP were at a moderately increased risk of having wheezing, asthma, eczema and allergic rhinitis during their childhood. Maternal stress during pregnancy might enhance the expression of asthma and atopic phenotypes in children. © 2012 John Wiley & Sons A/S.

Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors

NARCIS (Netherlands)

Jansen, P. L.; Chamuleau, R. A.; van Leeuwen, D. J.; Schipper, H. G.; Busemann-Sokole, E.; van der Heyde, M. N.

1990-01-01

Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single-photon computed tomography (SPECT), using 99mTc-colloid as tracer. The method was

Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Energy Technology Data Exchange (ETDEWEB)

Boukheris, Houda [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Stovall, Marilyn [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gilbert, Ethel S. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Stratton, Kayla L. [Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Smith, Susan A.; Weathers, Rita [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hammond, Sue [Department of Pathology, Ohio State University School of Medicine, Columbus, Ohio (United States); Mertens, Ann C. [Department of Pediatrics, Emory University, Atlanta, Georgia (United States); Donaldson, Sarah S. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Armstrong, Gregory T.; Robison, Leslie L. [Department of Epidemiology and Cancer Control, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Neglia, Joseph P. [Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Inskip, Peter D., E-mail: inskippe@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

2013-03-01

Purpose: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). Methods and Materials: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. Results: During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. Conclusion: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.

Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study

International Nuclear Information System (INIS)

Boukheris, Houda; Stovall, Marilyn; Gilbert, Ethel S.; Stratton, Kayla L.; Smith, Susan A.; Weathers, Rita; Hammond, Sue; Mertens, Ann C.; Donaldson, Sarah S.; Armstrong, Gregory T.; Robison, Leslie L.; Neglia, Joseph P.; Inskip, Peter D.

2013-01-01

Purpose: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). Methods and Materials: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. Results: During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. Conclusion: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

Science.gov (United States)

Firneisz, Gábor

2014-07-21

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

PROTECTIVE EFFECTS OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS AGAINST ALCOHOL-INDUCED LIVER INJURIES AND LIVER CANCERS IN RAT ANIMAL MODELS

Science.gov (United States)

Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K.

2014-01-01

Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol-feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased protein levels of triglyceride, hepatic stellate cell activation factors and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocelluar carcinoma, collagen deposition, numbers of preneoplastic foci, levels of hepatic stellate cell activation factors and catecholamines, as well as inflammatory milieu and the levels of NK cell cytotoxic factors in the liver. Conclusion These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and hepatocellular carcinoma formation possibly via influencing the immune function. PMID:25581653

Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion - preliminary report.

Science.gov (United States)

Laron, Zvi; Ginsberg, Shira; Webb, Muriel

2008-10-01

There is little information on the relationship between growth hormone/insulin-like growth factor-I (GH/IGF-I) deficiency or IGF-I treatment on nonalcoholic fatty liver disease (NAFLD) a disorder linked to obesity and insulin resistance. To find out whether the markedly obese patients with Laron syndrome (LS) and GH gene deletion have fatty livers. We studied 11 untreated adult patients with LS (5M, 6F), five girls with LS treated by IGF-I and five adult patients with GH gene deletion (3M, 3F), four previously treated by hGH in childhood. Fatty liver was quantitatively evaluated by ultrasonography using a phase array US system (HITACHI 6500, Japan). Body adiposity was determined by DEXA, and insulin resistance was estimated by HOMA-IR using the fasting serum glucose and insulin values. Six out of 11 adult patients with LS, two out of the five IGF-I treated girls with LS and three out of five adult hGH gene deletion patients were found to have NAFLD (nonalcoholic fatty liver disease). NAFLD is a frequent complication in untreated and treated congenital IGF-I deficiency. No correlation between NAFLD and age, sex, degree of obesity, blood lipids, or degree of insulin resistance was observed.

Liver cirrhosis and primary carcinoma of the liver among atomic bomb survivors. Study of autopsy cases

Energy Technology Data Exchange (ETDEWEB)

Hamada, T [Hiroshima Atomic Bomb Hospital (Japan)

1980-11-01

Liver cirrhosis and primary carcinoma of the liver were investigated in 1699 autopsies of atomic bomb survivors carried out in Hiroshima from 1956 to 1980. Liver cirrhosis, hepatocellular carcinoma and intrahepatic biliary carcinoma were observed in 116, 111, and 17 cases respectively, the ratios of man to woman and were 2.3, 3.9, and 1.8 with a mean age of 56, 60, and 67 years respectively. There was no evidence that exposure to a-bomb increased the risk of these diseases significantly. About 90% of the hepatocellular carcinomas was combined with liver cirrhosis. Weight of liver and spleen, amount of ascites, hemorrhage from the digestive canals, esophageal varix, combination with other diseases, and histologic correlation with the activities of HBs antigen and ..cap alpha..-fetoprotein were discussed with the relation to the exposure.

Liver hyperplasia and regression after lead nitrate administration

International Nuclear Information System (INIS)

Columbano, A.; Ledda-Columbano, G.M.; Coni, P.P.; Vargiu, M.; Faa, G.; Pani, P.

1984-01-01

The effect of a single intravenous injection of lead nitrate on liver, was investigated in male Wistar rats. Lead nitrate at 5 and 10 mumoles/100 g of body weight stimulated a 19-fold increase in the incorporation of 3 H-thymidine into liver DNA and resulted in temporal changes in DNA synthesis, as determined by assays of specific activity. Thirty-six hours after lead nitrate administration, the incorporation of 3 H-thymidine reached its maximum and returned to normal levels within 3 days. A significant increase in the number of cells entering mitosis at 36 hours indicated the capacity of lead to stimulate liver cell proliferation. Enlargement of the liver after lead treatment was also observed in both female Wistar rats as well in male Fischer rats. This stimulatory effect of lead on liver growth was reversible; during the involution of the liver, cell death morphologically similar to the one described as apoptosis was observed in histological sections of liver from animals sacrificed 4-7 days after lead treatment

Does the earned income tax credit increase children's weight? The impact of policy-driven income on childhood obesity.

Science.gov (United States)

Jo, Young

2018-07-01

I exploit substantial increases in the earned income tax credit to study how a policy-driven change in family income affects childhood obesity. Using the National Longitudinal Survey of Youth 1979, my difference-in-differences estimates indicate that the probability of being obese increased by 3 percentage points among children whose families experienced a greater income shock. A further investigation suggests that a reduction in maternal time with children played a greater role in children's weight gain than income. The paper's finding shows that a program that is not designed for health purposes, such as earned income tax credit, can have unintended effects on health outcomes. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

HEMOSTATIC DISORDERS IN LIVER DISEASES

Directory of Open Access Journals (Sweden)

A. F. Minov

2010-01-01

Full Text Available The liver is an essential player in the pathway of coagulation in both primary and secondary hemostasis as it is the site of synthesis of all coagulation factors and their inhibitors. Liver diseases are associated with complex changes in coagulation and the delicate balance between pro and antithrombotic factors is preserved but reset to a lower level. There is growing evidence that portal and hepatic vein thrombosis is cause of disease progression in cirrhotic patients and worsens hemostatic abnormalities. These hemostatic abnormalities do not always lead to spontaneous bleeding, which may be triggered only by additional factors, such as infections. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. In patients with end stage liver disease liver transplantation is the only treatment available, which can restore normal hemostasis, and correct genetic clotting defects. During liver transplantation hemorrhage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis. 

Childhood adversity and conduct disorder: A developmental pathway to violence in schizophrenia.

Science.gov (United States)

Oakley, Clare; Harris, Stephanie; Fahy, Thomas; Murphy, Declan; Picchioni, Marco

2016-04-01

Both childhood adversity and conduct disorder are over-represented among adult patients with schizophrenia and have been proposed as significant factors that may increase the risk of violence. It is not known how childhood adversity and conduct disorder might interact to contribute towards an increased risk of violence in schizophrenia. This study aimed to explore the relationships between childhood adversity, conduct disorder and violence among men with schizophrenia. 54 male patients with schizophrenia from a range of inpatient and outpatient mental health services were assessed for exposure to a variety of childhood adversities, conduct disorder before the age of 15 and later violent behaviour in adulthood. Exposure to domestic violence during childhood was associated with an increased propensity to violence in adulthood. Symptoms of conduct disorder were associated both with cumulative exposure to childhood adversities and with later propensity to violence. The cumulative number of childhood adversities was associated with adult propensity to violence. This association was significantly attenuated by inclusion of conduct disorder in the model. This is the first study to demonstrate an association between childhood exposure to domestic violence and later violent behaviour in schizophrenia. Conduct disorder may mediate the association between cumulative childhood adversities and adult propensity to violence, indicating an indirect pathway. These results indicate a complex interplay between childhood adversity, conduct disorder and later violent behaviour in schizophrenia, and suggest that there may be shared aetiological risk factors on a common developmental pathway to violence. Copyright © 2016 Elsevier B.V. All rights reserved.

CHILDHOODS AND INTERPRETATIONS: RESEARCH ON ATTITUDES TOWARDS CONTEMPORARY DISCOURSES ON CHILDHOOD

Directory of Open Access Journals (Sweden)

Czető, Krisztina

2018-01-01

Full Text Available This study deals with the theoretical interpretations of childhoods in the twenty-first century, and presents the results of an exploratory research on students’ attitudes towards contemporary childhood discourses conducted in Hungarian secondary schools. In a narrative literature review, the developmental and the new social paradigms of childhood are discussed. In the quantitative part of the research, the participants’ (N=806 attitudes were measures by a four-dimension questionnaire. The results of the exploratory research show that there are three dominant themes in childhood discourses highly accepted by the research participants: childhood as a development, the motif of initiation and the social and cultural relativity of childhoods.

Intergenerational violence in Burundi: Experienced childhood maltreatment increases the risk of abusive child rearing and intimate partner violence

OpenAIRE

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 ...

Analyzing the Impact of Increasing Mechanical Index and Energy Deposition on Shear Wave Speed Reconstruction in Human Liver.

Science.gov (United States)

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

2015-07-01

Shear wave elasticity imaging (SWEI) has found success in liver fibrosis staging. This work evaluates hepatic SWEI measurement success as a function of push pulse energy using two mechanical index (MI) values (1.6 and 2.2) over a range of pulse durations. Shear wave speed (SWS) was measured in the livers of 26 study subjects with known or potential chronic liver diseases. Each measurement consisted of eight SWEI sequences, each with different push energy configurations. The rate of successful SWS estimation was linearly proportional to the push energy. SWEI measurements with higher push energy were successful in patients for whom standard push energy levels failed. The findings also suggest that liver capsule depth could be used prospectively to identify patients who would benefit from elevated output. We conclude that there is clinical benefit to using elevated acoustic output for hepatic SWS measurement in patients with deeper livers. Published by Elsevier Inc.

Parental rheumatoid arthritis and childhood epilepsy

DEFF Research Database (Denmark)

Rom, Ane Lilleøre; Wu, Chunsen; Olsen, Jørn

2016-01-01

OBJECTIVE: To assess the influence of parental rheumatoid arthritis (RA) on risk of epilepsy. METHODS: We performed a nationwide cohort study including all singletons born in Denmark from 1977 to 2008 (n = 1,917,723) through individual linkage to nationwide Danish registries. The children were...... followed for an average of 16 years. Main outcome measures were adjusted hazard ratios (HRs) for epilepsy with onset in early childhood (29 days-4 years), late childhood (5-15 years), adolescence/adulthood (≥15 years), and at any age until the end of follow-up (December 31, 2010). RESULTS: Compared...... to unexposed children, children exposed to maternal RA had an increased risk of early and late childhood epilepsy (adjusted HRs 1.34 [95% confidence interval (CI) 1.13-1.60] and 1.26 [95% CI 1.13-1.41]), while children exposed to maternal RA had no increased risk of epilepsy in adolescence/adulthood (HR 1...

Childhood Cancer Statistics

Science.gov (United States)

... Watchdog Ratings Feedback Contact Select Page Childhood Cancer Statistics Home > Cancer Resources > Childhood Cancer Statistics Childhood Cancer Statistics – Graphs and Infographics Number of Diagnoses Incidence Rates ...

Home management of childhood diarrhoea among mothers in ...

African Journals Online (AJOL)

Diarrhoea diseases are major causes of childhood morbidity and mortality in developing countries. Treatment guidelines by the World Health Organization indicate that most cases of childhood diarrhoea can be treated at home by increased fluid intake and continued feeding during diarrhoea episodes. The aim of this study ...

Liver Hemangioma

Science.gov (United States)

Liver hemangioma Overview A liver hemangioma (he-man-jee-O-muh) is a noncancerous (benign) mass in the liver. A liver hemangioma is made up of a tangle of blood vessels. Other terms for a liver hemangioma are hepatic hemangioma and cavernous hemangioma. Most ...

Association of Adverse Childhood Experiences with Co-occurring Health Conditions in Early Childhood.

Science.gov (United States)

Bright, Melissa A; Thompson, Lindsay A

2018-01-01

To understand how adverse childhood experiences (ACEs) are associated with co-occurring physical, mental and developmental problems during early childhood. A subsample of 19,957 children aged 2-5 years were selected from the 2011-2012 National Survey for Child Health. Outcomes included 18 health conditions organized in singular condition domains (physical, mental, and developmental), and combinations of condition domains (e.g., physical plus mental, mental plus developmental, etc.). Predictors included 8 ACEs (divorce of a parent, death of a parent, exposure to domestic violence, living with someone with a drug or alcohol abuse problem, household member with a mental illness, parent incarceration, neighborhood violence, discrimination). Multivariable logistic regression was performed controlling for demographic characteristics, having a personal doctor, health insurance coverage, and seeing a health care professional in the previous year. Experiencing 3 or more ACEs before the age of 5 years was associated with increased likelihood of nearly every co-occurring condition combination across 3 domains of health. Most notably, experiencing 3 or more ACEs was also associated with a 2-fold increase in likelihood of having ≥1 physical condition and ≥1 developmental condition, a 9-fold increase in likelihood of having ≥1 mental and ≥1 developmental condition, and a 7-fold increase in likelihood of having ≥1 physical, ≥1 mental, and ≥1 developmental condition. This study demonstrates that we can identify the health effects of adversity quite early in development and that management should include communication between both health care and early childhood education providers.

Late effects of childhood leukemia therapy.

Science.gov (United States)

Fulbright, Joy M; Raman, Sripriya; McClellan, Wendy S; August, Keith J

2011-09-01

As survival rates for children treated for childhood cancers become significantly better, the focus is increasingly on determining the late effects of treatments and the best ways to monitor for them and prevent their occurrence. This review focuses on recent literature discussing the late effects of treatment in patients treated for acute myeloid leukemia and acute lymphoblastic leukemia during childhood. The late effects of therapy for childhood leukemia include secondary malignancy, cardiotoxicity, obesity, endocrine abnormalities, reproductive changes, neurocognitive deficits, and psychosocial effects. As clinicians have become more aware of the late effects of therapy, treatment regimens have been changed to decrease late effects, but patients still require long-term follow-up for their prevention and treatment.

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

Science.gov (United States)

Perumpail, Brandon J; Khan, Muhammad Ali; Yoo, Eric R; Cholankeril, George; Kim, Donghee; Ahmed, Aijaz

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis. PMID:29307986

Fallout, radiation doses near Dounreay, and childhood leukaemia

International Nuclear Information System (INIS)

Darby, S.C.; Doll, Richard

1987-01-01

Possible explanations for the recently reported increased incidence of childhood leukaemia around Dounreay were examined in the light of changes in the national incidence of leukaemia that occurred during the period of exposure to fallout from international testing of nuclear weapons in the atmosphere. It was concluded that the increase could not be accounted for by underestimate of the risk of leukaemia per unit dose of radiation at low doses and low dose rates, nor by underestimate of the relative biological efficiency of high compared with low linear energy transfer radiation. One possible explanation was underestimation of doses to the red bone marrow due to the discharges at Dounreay relative to dose from fallout, though investigation of ways in which this might have occurred did not suggest anything definite. Other explanations included a misconception of the site of origin of childhood leukaemia, outbreaks of an infectious disease and exposure to other, unidentified environmental agents. These findings weigh against the hypothesis that the recent increase in childhood leukaemia near Dounreay might be accounted for by radioactive discharges from nuclear plants, unless the doses to the stem cells from which childhood leukaemia originates have been grossly underestimated. (author)

Endocrine-Manifestations of Cirrhosis and Liver Disease

Directory of Open Access Journals (Sweden)

M Khalili

2014-04-01

Full Text Available The liver is involved in the synthesis and metabolism of many kinds of hormones, various abnormalities hormone levels are found in advanced liver disease. For example the liver is, extremely sensitive to changes in insulin or glucagon levels. The liver is the primary organ of iron storage is frequently involved, diabetes is common in patients with iron overload and may be seen in cirrhosis. Chronic infection with HCV is associated with insulin resistance. Thyroid disease often accompanies chronic hepatitis C infection .Anti thyroid autoantibodies are also found in chronic HCV infection. Nonalcoholic liver disease (NAFLDas a most common cause of chronic liver disease in western world ,as well accompanied by Type 2 diabetes and hyperlipidemia. Hypopituitarism and hypothyroidism also have been in NAFLD.The patients with NAFLD and Hypopituitarism may be susceptible to central obesity, dyslipidemia and insulin resistance leading to disease progression. Hepatic cirrhosis as the end stage of chronic liver disease is also associated with hypogonadism and signs of feminization. The peripheral metabolism of steroids is altered in many of hypogonadism, low testosterone level decreased libido, infertility, reduced secondary sex hair and gynecomastia, reduced spermatogenesis and peritubular fibrosis are found in men with cirrhosis .The normal function of the hypothalamic-pituitary gonadal axis is affected in liver disease. In cirrhotic patients the estrogen/androgen ratio is usually increased, the level of testosterone and dihydroepiandosteron are reduced while the estradiol level are normal or slightly elevated, these alterations are dependent on the severity of the liver disease.Succsesfull orthotropic liver transplantation  leads to improvement of the sex hormone disturbances. The pathogenesis of gynecomastia is due to the loss of equilibrium between estrogen and androgen caused by a feminizing state but it is due to increased estrogen precursor in

Predisposing Factors of Liver Necrosis after Transcatheter Arterial Chemoembolization in Liver Metastases from Neuroendocrine Tumor

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Joskin, Julien, E-mail: j.joskin@gmail.com; Baere, Thierry de, E-mail: Thierry.DEBAERE@igr.fr [Institut Gustave Roussy, Department of Interventional Radiology (France); Auperin, Anne, E-mail: Anne.AUPERIN@igr.fr [Institut Gustave Roussy, Department of Epidemiology (France); Tselikas, Lambros, E-mail: lambros.tselikas@gmail.com; Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr; Farouil, Geoffroy, E-mail: g.farouil@gmail.com [Institut Gustave Roussy, Department of Interventional Radiology (France); Boige, Valérie, E-mail: boige@igr.fr; Malka, David, E-mail: david.malka@igr.fr [Institut Gustave Roussy, Department of Digestive Oncology (France); Leboulleux, Sophie, E-mail: sophie.leboulleux@igr.fr [Institut Gustave Roussy, Department of Nuclear Medicine and Endocrine Oncology (France); Ducreux, Michel, E-mail: ducreux@igr.fr [Institut Gustave Roussy, Department of Digestive Oncology (France); Baudin, Eric, E-mail: baudin@igr.fr [Institut Gustave Roussy, Department of Nuclear Medicine and Endocrine Oncology (France); Deschamps, Frédéric, E-mail: frederic.deschamps@igr.fr [Institut Gustave Roussy, Department of Interventional Radiology (France)

2015-04-15

PurposeTo investigate predictive factors for liver necrosis after transcatheter arterial chemoembolization (TACE) of neuroendocrine liver metastases.MethodsA total of 164 patients receiving 374 TACE were reviewed retrospectively to analyze predictive factors of liver necrosis. We analyzed patient age and sex; metastasis number and location; percentage of liver involvement; baseline liver function test; and pretreatment imaging abnormalities such as bile duct dilatation (BDD), portal vein narrowing (PVN), and portal vein thrombosis (PVT). We analyzed TACE technique such as Lipiodol or drug-eluting beads (DEB) as the drug’s vector; dose of chemotherapy; diameter of DEB; and number, frequency, and selectivity of TACE.ResultsLiver necrosis developed after 23 (6.1 %) of 374 TACE. In multivariate analysis, DEB > 300 μm in size induced more liver necrosis compared to Lipiodol (odds ratio [OR] 35.20; p < 0.0001) or with DEB < 300 μm in size (OR 19.95; p < 0.010). Pretreatment BDD (OR 119.64; p < 0.0001) and PVT (OR 9.83; p = 0.030) were predictive of liver necrosis. BDD or PVT responsible for liver necrosis were present before TACE in 59 % (13 of 22) and were induced by a previous TACE in 41 % (9 of 22) of cases.ConclusionDEB > 300 μm in size, BDD, and PVT are responsible for increased rate of liver necrosis after TACE. Careful analysis of BDD or PVT on pretreatment images as well as images taken between two courses can help avoid TACE complications.

Liver Immunology

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Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

2014-01-01

The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

Developmental intrahepatic shunts of childhood: radiological features and management

International Nuclear Information System (INIS)

Paley, M.R.; Farrant, P.; Kane, P.; Karani, J.B.; Heaton, N.D.; Howard, E.R.

1997-01-01

The purpose of this study was to evaluate the role of radiological techniques in the diagnosis and management of developmental intrahepatic shunts. Hepatic vascular fistulae are recognised sequelae of liver trauma and intrahepatic tumours. However, there are rare developmental malformations which may present in childhood or later life and which may carry life-threatening complications. Retrospective analysis of clinical and radiological data was carried out in 24 patients. Anomalies evaluated were: (a) direct communication between hepatic artery and hepatic veins; (b) congenital hepatoportal arteriovenous malformations; and (c) congenital portocaval anastomosis with persistent flow through the ductus venosus. Although rare, the prompt recognition of these vascular anomalies allows early surgical or radiological intervention and reversal of the haemodynamic complications. (orig.)

Outcomes of liver-first strategy and classical strategy for synchronous colorectal liver metastases in Sweden.

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Valdimarsson, Valentinus T; Syk, Ingvar; Lindell, Gert; Norén, Agneta; Isaksson, Bengt; Sandström, Per; Rizell, Magnus; Ardnor, Bjarne; Sturesson, Christian

2018-05-01

Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection before resection of the primary cancer. The aim of this study was to compare outcomes in patients following the liver-first strategy and the classical strategy (resection of the bowel first) using prospectively registered data from two nationwide registries. Clinical, pathological and survival outcomes were compared between the liver-first strategy and the classical strategy (2008-2015). Overall survival was calculated. A total of 623 patients were identified, of which 246 were treated with the liver-first strategy and 377 with the classical strategy. The median follow-up was 40 months. Patients chosen for the classical strategy more often had T4 primary tumours (23% vs 14%, P = 0.012) and node-positive primaries (70 vs 61%, P = 0.015). The liver-first patients had a higher liver tumour burden score (4.1 (2.5-6.3) vs 3.6 (2.2-5.1), P = 0.003). No difference was seen in five-year overall survival between the groups (54% vs 49%, P = 0.344). A majority (59%) of patients with rectal cancer were treated with the liver-first strategy. The liver-first strategy is currently the dominant strategy for sCRLM in patients with rectal cancer in Sweden. No difference in overall survival was noted between strategies. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Childhood trauma and childhood urbanicity in relation to psychotic disorder

NARCIS (Netherlands)

Frissen, Aleida; Lieverse, Ritsaert; Drukker, Marjan; van Winkel, Ruud; Delespaul, Philippe; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Kahn, René; Meije, Carin; Myin-Germeys, Inez; van Os, Jim; Wiersma, Durk

2015-01-01

Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect of

Childhood trauma and childhood urbanicity in relation to psychotic disorder

NARCIS (Netherlands)

Frissen, Aleida; Lieverse, Ritsaert; Drukker, Marjan; van Winkel, Ruud; Delespaul, Philippe; Cahn, W

2015-01-01

BACKGROUND: Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect

Acetaminophen-induced acute liver injury in HCV transgenic mice

International Nuclear Information System (INIS)

Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

2013-01-01

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

Acetaminophen-induced acute liver injury in HCV transgenic mice

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Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tech, Katherine; Macdonald, Jeffrey M. [Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Boorman, Gary A. [Covance, Chantilly, VA 20151 (United States); Chatterjee, Saurabh; Mason, Ronald P. [Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, RTP, NC 27713 (United States); Melnyk, Stepan B. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72201 (United States); Tryndyak, Volodymyr P.; Pogribny, Igor P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)

2013-01-15

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

Science.gov (United States)

Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

2006-01-01

CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (Pphenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

Acetaldehyde Adducts in Alcoholic Liver Disease

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Mashiko Setshedi

2010-01-01

Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

Rising Rates of Hepatocellular Carcinoma Leading to Liver Transplantation in Baby Boomer Generation with Chronic Hepatitis C, Alcohol Liver Disease, and Nonalcoholic Steatohepatitis-Related Liver Disease.

Science.gov (United States)

Cholankeril, George; Yoo, Eric R; Perumpail, Ryan B; Liu, Andy; Sandhu, Jeevin S; Nair, Satheesh; Hu, Menghan; Ahmed, Aijaz

2017-09-26

We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945-1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts-the BB and non-BB-with a secondary diagnosis of HCV, ALD, or NASH. From 2003-2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well.

Whole of Systems Trial of Prevention Strategies for Childhood Obesity: WHO STOPS Childhood Obesity

Directory of Open Access Journals (Sweden)

Steven Allender

2016-11-01

Full Text Available Background: Community-based initiatives show promise for preventing childhood obesity. They are characterized by community leaders and members working together to address complex local drivers of energy balance. Objectives: To present a protocol for a stepped wedge cluster randomized trial in ten communities in the Great South Coast Region of Victoria, Australia to test whether it is possible to: (1 strengthen community action for childhood obesity prevention, and (2 measure the impact of increased action on risk factors for childhood obesity. Methods: The WHO STOPS intervention involves a facilitated community engagement process that: creates an agreed systems map of childhood obesity causes for a community; identifies intervention opportunities through leveraging the dynamic aspects of the system; and, converts these understandings into community-built, systems-oriented action plans. Ten communities will be randomized (1:1 to intervention or control in year one and all communities will be included by year three. The primary outcome is childhood obesity prevalence among grade two (ages 7–8 y, grade four (9–10 y and grade six (11–12 y students measured using our established community-led monitoring system (69% school and 93% student participation rate in government and independent schools. An additional group of 13 external communities from other regions of Victoria with no specific interventions will provide an external comparison. These communities will also allow us to assess diffusion of the intervention to control communities during the first three years of the trial. Conclusion: This trial will test effectiveness, over a five-year period, of community-owned, -supported and -led strategies designed to address complex and dynamic causes of childhood obesity.

Estimation of liver glucose metabolism after refeeding

International Nuclear Information System (INIS)

Rognstad, R.

1987-01-01

Refeeding or infusing glucose to rats fasted for 24 hr or more causes rapid liver glycogen synthesis, the carbon source now considered to be largely from gluconeogenesis. While substrate cycling between plasma glucose and liver glucose-6P is known to occur, this cycling has apparently been ignored when calculations are made of % contribution of direct and indirect pathways to liver glycogen synthesis, or when hepatic glucose output is calculated from glucose turnover minus the glucose infusion rate. They show that, isotopically, an estimate of the fluxes of liver glucokinase and glucose-6-phosphatase is required to quantitate sources of carbon for liver glycogen synthesis, and to measure hepatic glucose output (or uptake). They propose a method to estimate these fluxes, involving a short infusion of a 14 C labelled gluconeogenic precursor plus (6T)glucose, with determination of isotopic yields in liver glycogen and total glucose. Given also the rate of liver glycogen synthesis, this procedure permits the estimation of net gluconeogenesis and hepatic glucose output or uptake. Also, in vitro evidence against the notion of a drastic zonation of liver carbohydrate metabolism is presented, e.g. raising the glucose concentration from 10 to 25 mM increases the 14 C yield from H 14 CO 3 - in lactate, with the increased pyruvate kinase flux and decreased gluconeogenesis occurring in the same cell type, not opposing pathways in different hepatocyte types (as has been postulated by some to occur in vivo after refeeding

[Jaundice and pathological liver values].

Science.gov (United States)

Schwarzenbach, Hans-Rudolf

2013-06-05

Jaundice corresponds to elevated bilirubin- levels, whereat one has to distinguish between direct and indirect serum-bilirubin. In the present Mini Review causes and differential diagnosis of jaundice are outlined. Ultrasound-diagnostic plays a major role in identifying intrahepatic or extrahepatic jaundice. Attention is given to the differential diagnosis of elevated liver enzymes in presence of jaundice, pointing out the distinction between hepatocellular and cholestatic parameters as well as the differentiation in acute or chronic increase. Moreover, the consequences of liver enzyme elevations including further diagnostic procedures, are highlighted. Finally, possibilities and limitations of modern diagnostic tests for liver fibrosis are briefly overviewed.

Epidemiology Of Alcoholic Liver Disease

Directory of Open Access Journals (Sweden)

А.Г. Мартынова

2009-12-01

Full Text Available One of the main factors of chronic liver disease is alcohol. The level of alcoholic liver disease incidence and cirrhosis mortality has increased considerably in the recent years in many countries. The risk of development and disease progression are determined by the effect of endogenous and exogenous factors: "drinking mode", female gender, heredity and genetic predisposition, obesity, concomitant viral hepatitis

Increased risk for complications following removal of hardware in patients with liver disease, pilon or pelvic fractures: A regression analysis.

Science.gov (United States)

Brown, Bryan D; Steinert, Justin N; Stelzer, John W; Yoon, Richard S; Langford, Joshua R; Koval, Kenneth J

2017-12-01

Indications for removing orthopedic hardware on an elective basis varies widely. Although viewed as a relatively benign procedure, there is a lack of data regarding overall complication rates after fracture fixation. The purpose of this study is to determine the overall short-term complication rate for elective removal of orthopedic hardware after fracture fixation and to identify associated risk factors. Adult patients indicated for elective hardware removal after fracture fixation between July 2012 and July 2016 were screened for inclusion. Inclusion criteria included patients with hardware related pain and/or impaired cosmesis with complete medical and radiographic records and at least 3-month follow-up. Exclusion criteria were those patients indicated for hardware removal for a diagnosis of malunion, non-union, and/or infection. Data collected included patient age, gender, anatomic location of hardware removed, body mass index, ASA score, and comorbidities. Overall complications, as well as complications requiring revision surgery were recorded. Statistical analysis was performed with SPSS 20.0, and included univariate and multivariate regression analysis. 391 patients (418 procedures) were included for analysis. Overall complication rates were 8.4%, with a 3.6% revision surgery rate. Univariate regression analysis revealed that patients who had liver disease were at significant risk for complication (p=0.001) and revision surgery (p=0.036). Multivariate regression analysis showed that: 1) patients who had liver disease were at significant risk of overall complication (p=0.001) and revision surgery (p=0.039); 2) Removal of hardware following fixation for a pilon had significantly increased risk for complication (p=0.012), but not revision surgery (p=0.43); and 3) Removal of hardware for pelvic fixation had a significantly increased risk for revision surgery (p=0.017). Removal of hardware following fracture fixation is not a risk-free procedure. Patients with

Stress and childhood epilepsy

NARCIS (Netherlands)

Campen, J.S. van

2015-01-01

Epilepsy is one of the most common chronic diseases in childhood, characterized by the enduring predisposition to generate epileptic seizures. Children with epilepsy and their parents often report seizures precipitated by stress. In order to increase our understanding of the pathophysiological

(1)H-MRS measured ectopic fat in liver and muscle is associated with the metabolic syndrome in Danish girls but not in boys with overweight and obesity

DEFF Research Database (Denmark)

Nissen, A; Fonvig, Cilius E; Chabanova, E.

2016-01-01

BACKGROUND: The metabolic syndrome (MetS) is a complication to overweight and obesity, which can be observed already in childhood. Ectopic lipid accumulation in muscle and liver has been shown to associate with the development of insulin resistance and dyslipidemia. Thus, the interaction between...

Childhood Obesity Facts

Science.gov (United States)

... and Local Programs Related Topics Diabetes Nutrition Childhood Obesity Facts Recommend on Facebook Tweet Share Compartir On ... Children (WIC) Program, 2000-2014 Prevalence of Childhood Obesity in the United States Childhood obesity is a ...

[Effect of hepatic resection on development of liver metastasis].

Science.gov (United States)

García-Alonso, I; Palomares, T; Alonso, A; Portugal, V; Castro, B; Caramés, J; Méndez, J

2003-11-01

In the early stages of metastasis, development of the disease is dependent on growth factors produced by the host. There are clinical situations associated with an increase in these factors, such as partial resection of metastasized liver. Given the important role of hepatotrophic factors in liver regeneration, we have studied the effect of partial hepatectomy on the development of residual micrometastases in the liver, and on the neoplastic process as a whole. We used a murine model in which a rabdomiosarcoma was established by subcutaneous inoculation of syngeneic tumor cells in male Wag rats. Subsequently, the primary tumor was resected and/or a 40% hepatectomy was performed. The effect of these two surgical procedures on the tumor process was analyzed on the 25th and 35th days post-inoculation, and the percentage of regenerating hepatocytes was assessed. Both the tumorectomy and liver resection, when not combined, produced an increase in regional adenopathies without modifying the evolution of metastasis in the liver. However, when tumor excision and partial hepatectomy were performed simultaneously, there was a net increase in the metastatic process. In addition to a rapid spread of the disease (lung, mediastinum, retroperitoneum), the number of liver metastases increased by 300%. This development coincided with a steep rise in the percentage of regenerating hepatocytes, which nearly doubled that of the group subjected only to liver resection. We conclude that liver resection, alone or combined with excision of the primary tumor, may enhance tumor progression, both locally and at the metastasic level.

High concordance of subtypes of childhood acute lymphoblastic leukemia within families

DEFF Research Database (Denmark)

Schmiegelow, K.; Thomsen, U Lautsen; Baruchel, A

2012-01-01

Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk...

EX VIVO STUDY OF QUANTITATIVE ULTRASOUND PARAMETERS IN FATTY RABBIT LIVERS

Science.gov (United States)

Ghoshal, Goutam; Lavarello, Roberto J.; Kemmerer, Jeremy P.; Miller, Rita J.; Oelze, Michael L.

2012-01-01

Nonalcoholic fatty liver disease (NAFLD) affects more than 30% of Americans, and with increasing problems of obesity in the United States, NAFLD is poised to become an even more serious medical concern. At present, accurate classification of steatosis (fatty liver) represents a significant challenge. In this study, the use of high-frequency (8 to 25 MHz) quantitative ultrasound (QUS) imaging to quantify fatty liver was explored. QUS is an imaging technique that can be used to quantify properties of tissue giving rise to scattered ultrasound. The changes in the ultrasound properties of livers in rabbits undergoing atherogenic diets of varying durations were investigated using QUS. Rabbits were placed on a special fatty diet for 0, 3, or 6 weeks. The fattiness of the livers was quantified by estimating the total lipid content of the livers. Ultrasonic properties, such as speed of sound, attenuation, and backscatter coefficients, were estimated in ex vivo rabbit liver samples from animals that had been on the diet for varying periods. Two QUS parameters were estimated based on the backscatter coefficient: effective scatterer diameter (ESD) and effective acoustic concentration (EAC), using a spherical Gaussian scattering model. Two parameters were estimated based on the backscattered envelope statistics (the k parameter and the μ parameter) according to the homodyned K distribution. The speed of sound decreased from 1574 to 1565 m/s and the attenuation coefficient increased from 0.71 to 1.27 dB/cm/MHz, respectively, with increasing fat content in the liver. The ESD decreased from 31 to 17 μm and the EAC increased from 38 to 63 dB/cm3 with increasing fat content in the liver. A significant increase in the μ parameter from 0.18 to 0.93 scatterers/mm3 was observed with increasing fat content in the liver samples. The results of this study indicate that QUS parameters are sensitive to fat content in the liver. PMID:23062376

Increased transcapillary escape rate of albumin in patients with cirrhosis of the liver

DEFF Research Database (Denmark)

Parving, H H; Ranek, L; Lassen, N A

1977-01-01

The transcapillary escape rate of albumin (TERalb), i.e. the fraction of intravascular mass of albumin that passes to the extravascular space per unit time, was determined from the disappearance of intravenously injected 125I-labelled human serum albumin during the first 60 min after injection...... in nine patients with cirrhosis of the liver. Six of the patients had ascites. The wedged hepatic venous pressure or splenic pulp pressure ranged from 20 to 30 mmHg, mean 26 mmHg. Plasma albumin concentration was low, but plasma volume was slightly enlarged, and thus the intravascular mass of albumin...... was only moderately reduced. The transcapillary escape rate of albumin was significantly elevated in all the cirrhotics, mean 10.2%/h, range 8.8 to 12.3%/h, in comparison to values for twenty-eight normal subjects 5.4%/h, range 3.5-7.2%/h. Our results can best be explained by increased filtration out...

Human germline hedgehog pathway mutations predispose to fatty liver.

Science.gov (United States)

Guillen-Sacoto, Maria J; Martinez, Ariel F; Abe, Yu; Kruszka, Paul; Weiss, Karin; Everson, Joshua L; Bataller, Ramon; Kleiner, David E; Ward, Jerrold M; Sulik, Kathleen K; Lipinski, Robert J; Solomon, Benjamin D; Muenke, Maximilian

2017-10-01

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway. Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2 +/- ) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2 +/- mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2 +/- mice exposed to a high-fat diet. Our results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous

Percutaneous Liver Biopsy after Living Donor Liver Transplantation Resulting in Fulminant Hepatic Failure: The First Reported Case of Hepatic Compartment Syndrome

Directory of Open Access Journals (Sweden)

Nicholas N. Nissen

2010-01-01

Full Text Available A 28-year-old female who underwent live donor liver transplantation 3 years prior presented after percutaneous liver biopsy with abdominal and shoulder pain, nausea, vomiting, and elevated liver enzymes. Computed tomography (CT showed an intrahepatic and subcapsular hematoma. There was a progressive increase in liver enzymes, bilirubin, and INR and a decline in hemoglobin. Subsequent CT imaging revealed flattening of the portal vein consistent with compression by the enlarging hematoma. Liver failure ensued and the patient required urgent retransplantation. The explant demonstrated ischemic necrosis of greater than 90% of the liver parenchyma. We report this case of “Hepatic Compartment Syndrome” leading to fulminant hepatic failure.

Liver transplantation in polycystic liver disease

DEFF Research Database (Denmark)

Krohn, Paul S; Hillingsø, Jens; Kirkegaard, Preben

2008-01-01

OBJECTIVE: Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about...... whether it is a relevant modality considering the absence of liver failure, relative organ shortage, perioperative risks and lifelong immunosuppression. The purpose of this study was to review our experience of LTX for PLD and to compare the survival with the overall survival of patients who underwent LTX...... from 1992 to 2005. MATERIAL AND METHODS: A retrospective study of the journals of 440 patients, who underwent 506 LTXs between 1992 and 2005, showed that 14 patients underwent LTX for PLD. All patients had normal liver function. Three were receiving haemodialysis and thus underwent combined liver...

Enhancement of liver regeneration and liver surgery

NARCIS (Netherlands)

Olthof, P.B.

2017-01-01

Liver regeneration allows surgical resection of up to 75% of the liver and enables curative treatment potential for patients with primary or secondary hepatic malignancies. Liver surgery is associated with substantial risks, reflected by considerable morbidity and mortality rates. Optimization of

Maternal sensitivity and social support protect against childhood atopic dermatitis

OpenAIRE

Letourneau, Nicole L.; Kozyrskyj, Anita L.; Cosic, Nela; Ntanda, Henry N.; Anis, Lubna; Hart, Martha J.; Campbell, Tavis S.; Giesbrecht, Gerald F.

2017-01-01

Background Many studies have identified associations between qualities of maternal?child relationships and childhood asthma, but few have examined associations with childhood atopic dermatitis (AD), a common precursor to asthma. Moreover, maternal psychological distress, including prenatal and postnatal depression, anxiety and stress, may increase risk, while social support from partners may reduce risk for childhood AD. We sought to uncover the association between maternal?infant relationshi...

Study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings

International Nuclear Information System (INIS)

Yang, Jeong Hwa

2006-01-01

The study obtained the following conclusions by making a comparative study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings. I surveyed the value of abdominal ultrasound in 400 patients without clinical symptoms at C Health Clinic Center, Seoul. Compare with blood pressure was high (systolic/diastolic) in 7.5%/4.5% on persons who were diagnosed fatty liver. At the time of the diagnosis, Total cholesterol level was increased in fatty liver patients, HDL-cholesterol level was high in fatty liver patients. And Trigryceride level was increased in fatty liver persons, LDL-cholesterol was high in fatty liver persons. SGOT level was increased in 5.5% on patients who were diagnosed fatty liver, 0% on persons who were normal and SGPT level was high in 29.5% on people who were diagnosed fatty liver, 0% on patients who were diagnosed normal

Study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings

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Yang, Jeong Hwa [Cheju Halla College, Cheju (Korea, Republic of)

2006-03-15

The study obtained the following conclusions by making a comparative study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings. I surveyed the value of abdominal ultrasound in 400 patients without clinical symptoms at C Health Clinic Center, Seoul. Compare with blood pressure was high (systolic/diastolic) in 7.5%/4.5% on persons who were diagnosed fatty liver. At the time of the diagnosis, Total cholesterol level was increased in fatty liver patients, HDL-cholesterol level was high in fatty liver patients. And Trigryceride level was increased in fatty liver persons, LDL-cholesterol was high in fatty liver persons. SGOT level was increased in 5.5% on patients who were diagnosed fatty liver, 0% on persons who were normal and SGPT level was high in 29.5% on people who were diagnosed fatty liver, 0% on patients who were diagnosed normal.

Coffee and liver health.

Science.gov (United States)

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.

Improved noninvasive prediction of liver fibrosis by liver stiffness measurement in patients with nonalcoholic fatty liver disease accounting for controlled attenuation parameter values.

Science.gov (United States)