Unraveling the Potential Role of Tecomella undulata in Experimental NASH.

The pathophysiology of nonalcoholic steatohepatitis (NASH) is complex, owing to its diverse pathological drivers and, until recently, there were no approved drugs for this disease. Tecomella is a popular herbal medicine used to treat hepatosplenomegaly, hepatitis, and obesity. However, the potential role of Tecomella undulata in NASH has not yet been scientifically investigated. The administration of Tecomella undulata via oral gavage lowered body weight, insulin resistance, alanine transaminase (ALT), aspartate transaminase (AST), triglycerides, and total cholesterol in western diet sugar water (WDSW) fed mice but had no effect on chow diet normal water (CDNW) fed mice. Tecomella undulata improved steatosis, lobular inflammation, and hepatocyte ballooning and resolved NASH in WDSW mice. Furthermore, Tecomella undulata also alleviated the WDSW-induced Endoplasmic Reticulum stress and oxidative stress, enhanced antioxidant status, and thus reduced inflammation in the treated mice. Of note, these effects were comparable to saroglitazar, the approved drug used to treat human NASH and the positive control used in the study. Thus, our findings indicate the potential of Tecomella undulata to ameliorate WDSW-induced steatohepatitis, and these preclinical data provide a strong rationale for assessing Tecomella undulata for the treatment of NASH.

Metabolic assessment in children with neuromuscular disorders shows risk of liver enlargement, steatosis and fibrosis.

AIM: The aim of this study was to conduct a metabolic and nutritional assessment of children with neuromuscular disorders, including the investigation of the liver and bone mineral density. METHODS: In this observational study, we included 44 children with neuromuscular disorders. The nutritional status, bone health and liver were assessed by ultrasound, transient elastography, dual X-ray absorptiometry scan, blood samples, anthropometric measurements and 3-day diet registration. RESULTS: Liver involvement was found in 31.0%: liver enlargement in 7.1%, steatosis in 4.8%, fibrosis in 14.3% and liver enlargement together with steatosis or fibrosis was found in 4.8%. These changes were found in 9/23 patients with Duchenne muscular dystrophy, 4/9 patients with spinal muscular atrophy type II and 0/12 patients with other neuromuscular diagnoses. Low bone mineral density was found in 44.0% of the patients, though the majority used daily vitamin D and calcium supplements. Vitamin D insufficiency or deficiency was found in 22.6%. CONCLUSION: The metabolic assessment in children with neuromuscular disorders shows an increased risk of liver enlargement, steatosis and fibrosis. Possible causes are obesity, decreased mobility, low skeletal muscle mass and for a subgroup the use of glucocorticoids. The findings suggest that monitoring liver function should be part of the nutritional assessment in patients with neuromuscular disorders.

The cooperative interplay among inflammation, necroptosis and YAP pathway contributes to the folate deficiency-induced liver cells enlargement.

Change in cell size may bring in profound impact to cell function and survival, hence the integrity of the organs consisting of those cells. Nevertheless, how cell size is regulated remains incompletely understood. We used the fluorescent zebrafish transgenic line Tg-GGH/LR that displays inducible folate deficiency (FD) and hepatomegaly upon FD induction as in vivo model. We found that FD caused hepatocytes enlargement and increased liver stiffness, which could not be prevented by nucleotides supplementations. Both in vitro and in vivo studies indicated that RIPK3/MLKL-dependent necroptotic pathway and Hippo signaling interactively participated in this FD-induced hepatocytic enlargement in a dual chronological and cooperative manner. FD also induced hepatic inflammation, which convenes a dialog of positive feedback loop between necroptotic and Hippo pathways. The increased MMP13 expression in response to FD elevated TNFα level and further aggravated the hepatocyte enlargement. Meanwhile, F-actin was circumferentially re-allocated at the edge under cell membrane in response to FD. Our results substantiate the interplay among intracellular folate status, pathways regulation, inflammatory responses, actin cytoskeleton and cell volume control, which can be best observed with in vivo platform. Our data also support the use of this Tg-GGH/LR transgenic line for the mechanistical and therapeutic research for the pathologic conditions related to cell size alteration.

Efficacy And Tolerability Of Oral Iron Chelator, Deferasirox.

BACKGROUND: Thalassemia major is the severe form of ß thalassemia characterized by severe anaemia, hepatosplenomegaly and facioskeletal changes due to increased haemolysis of defective red blood cells. In iron overload states, high levels of iron exceed the iron-carrying capacity of transferrin within the plasma, leading to the formation of nontransferrin-bound iron form. These nontransferrin-bound iron forms can be taken up into cells, including liver, heart, and endocrine cells leading to organ damage. To prevent complications associated with hemosiderosis, iron chelation therapy remains one of the main objectives of clinical management of the patients affected by Thalassemia Major. METHODS: Thirty-seven patients were enrolled using non randomized convenience sampling technique after the written consent from patients. Patients age 2-30 years were enrolled in this study. Serum Ferritin, ALT, Serum Creatinine were checked at the start of the study, 3 months, 6months and then at the end of the study, i.e., at 9 months of the commencement of the study. They were also assessed for other side effects pertaining to oral tolerability of the drug like vomiting, nausea, GI upset, diarrhoea, urinary complaints or any other subjective complaint. RESULTS: Of the 37 patients, 20 were male (54.1%) and 17 were female (45.9%). Mean age of the patients was 10.2 years (Min. 3 years, Max 21 years). The average serum Ferritin at baseline was noted as 3440 which increased after a period of 3 months, 6 months and 9 months with average of 3359, 3677 and 4394 respectively. After the period of 9 months largest 95% confidence interval of serum Ferritin levels was observed in the range of 3420.17 to 5368.63. In our study, 17 patients required alternative chelation (46%). These patients needed IV Deferioxamine because of the rising trend of Serum Ferritin after the study. CONCLUSIONS: From the results of our study, we infer that oral Deferasirox is not an effective iron chelator. If the patients are taking oral deferasirox, their Serum Ferritin should be checked 3 monthlies. The drug is effective only in maintaining Serum Ferritin levels with levels less than 1500ng/ml. Intravenous Deferioxamine still should be preferred over oral iron chelators for effective control of iron overload and its complications.

Schisandrol B promotes liver enlargement via activation of PXR and YAP pathways in mice.

BACKGROUND: Schisandrol B (SolB) is one of the bioactive components from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. It has been demonstrated that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. It was found that SolB can induce hepatomegaly but the involved mechanisms remain unknown. PURPOSE: This study aimed to explore the mechanisms involved in SolB-induced hepatomegaly. METHODS: Male C57BL/6 mice were injected intraperitoneally with SolB (100 mg/kg) for 5 days. Serum and liver samples were collected for biochemical and histological analyses. The mechanisms of SolB were investigated by qRT-PCR and western blot analyses, luciferase reporter gene assays and immunofluorescence. RESULTS: SolB significantly increased hepatocyte size and proliferation, and then promoted liver enlargement without liver injury and inflammation. SolB transactivated human PXR, activated PXR in mice and upregulated hepatic expression of its downstream proteins, such as CYP3A11, CYP2B10 and UGT1A1. SolB also significantly enhanced nuclear translocation of PXR and YAP in human cell lines. YAP signal pathway was activated by SolB in mice. CONCLUSION: These findings demonstrated that SolB can significantly induce liver enlargement, which is associated with the activation of PXR and YAP pathways.

Ethanolic extract of Salacia nitida root bark ameliorates lipid peroxidation and hepatosplenomegaly in Plasmodium berghei-malaria infected mice.

The root bark of Salacia nitida L.benth (celastraceae) is used as remedy for malaria and typhoid fever in Southern part of Nigeria. This study is designed to evaluate the effect of treatment with ethanolic extract from root bark of S. nitida on lipid peroxidation, hepatomegaly and splenomegaly in Plasmodium berghei-malaria infected mice. Thirty malaria-infected and six uninfected mice were used for the study. 280, 430, and 580 mg kg-1 body weight day-1 of ethanolic extract and 4 mg kg-1 body weight day-1 of artesunate were administered orally to infected mice in groups B, C, D, and E, while 4 ml kg-1 body weight day-1 of physiological saline was given to infected untreated mice in group A and the uninfected untreated mice in group F. Treatments were done for five days. Levels of malondialdehyde were measured as means of assessing lipid peroxidation in the experimental animals. Weights of experimental animals, liver, and spleen, and the length of spleen from experimental animals were also measured. Animal's liver and spleen-body weight ratios were determined. Results from the study showed significant decrease (P < 0.05) in levels of malondialdehyde, and significant increase (P < 0.05) in body weights. Also, significant decreases (P < 0.05) were seen in the weights of liver and spleen, lengths of spleen, and organ-body weight ratios of malaria-infected treated mice. Therefore, this study confirmed that ethanolic extract from root bark of S. nitida is effective in the treatment of malaria, as it is seen in its ability to attenuate lipid peroxidation and hepatosplenomegaly in mice, thus corroborating its traditional use for the treatment of malaria.

Hepatoesplenomegalia relacionada a linfoma de Burkitt en paciente pediátrico / Hepatoesplenomegalia related to Burkitt´s lymphoma in a pediatric patient

RESUMEN El linfoma de Burkitt, se trata de un subtipo poco frecuente del linfoma no Hodgkin, con elevada frecuencia en aquellos pacientes con sida. La hepatoesplenomegalia es un signo clínico de gran importancia para el diagnóstico oportuno de algunas patologías; entre los mecanismos de formación de la hepatoesplenomegalia se encuentra la infiltración celular, ocasionada por la migración de células tumorales. Se presenta por inflamaciones debido a la presencia de infecciones por virus o bacterias las cuales son muy comunes en pacientes con sida. Se presentó un caso de un paciente masculino de 4 años, diagnosticado con VIH positivo, con la configuración correspondiente de criterios clínicos en clasificación C para sida. El cual desarrolló a nivel de cavidad oral un Burkitt primario, que se acompañó de hepatoesplenomegalia. Se pretendió describir la relación y el comportamiento de este tipo de linfoma con la hepatoesplenomegalia, así como la repercusión a nivel del sistema estomatognático, a nivel sistémico y el plan de tratamiento. Por el cuadro clínico e inmunológico del paciente estudiado, se planteó un pronóstico reservado por presentar un cuadro clínico infrecuente, en el que se observó Burkitt; tanto a nivel del sistema estomatognático como a nivel abdominal. Se hizo necesario realizar un diagnóstico oportuno y certero para iniciar el tratamiento a tiempo, se comenzó inmediatamente con tratamiento (AU).

ABSTRACT Burkitt lymphoma (BL) is a rare subtype of non-Hodgkin lymphoma, with high frequency in those patients with AIDS. Hepatosplenomegaly is a clinical sign of great importance for the timely diagnosis of some pathologies; cellular infiltration is found among the mechanisms of hepatosplenomegaly formation; it is caused by the migration of tumor cells. It emerges by inflammations due to the presence of infections by virus or bacteria which are very common in patients with AIDS. The authors present the case of a male patient, aged 4 years, with a positive HIV diagnosis, and the correspondent configuration of clinical criteria in C classification for AIDS, who developed a primary Burkitt lymphoma at the level of oral cavity We present the case of a 4-year-old male patient diagnosed with HIV positive, with the corresponding configuration of clinical criteria in classification C for AIDS; who developed a primary LB at the oral cavity level that was accompanied by hepatosplenomegaly. The authors pretended to describe the relation and behavior of this kind of lymphoma with hepatosplenomegaly, and also the repercussion at the stomatognathic level, at the systemic level and the treatment plan. Due to the clinical and immunological characteristics of the studied patient a reserved prognosis was given because of presenting infrequent clinical characteristics in which a Burkitt was observed both, at the stomatognathic and at the abdominal level. It was necessary to make an opportune and accurate diagnosis to begin the treatment on time (AU).

Estudios de la naturaleza de la Efectividad y Dirección Funcional de Suplemento Biológicamente Activo en el Tratamiento Integral de la Hepatitis Alcohólica Aguda / Nature Studies of the Effectiveness and Functional Direction of Biologically Active Supplement in Comprehensive Treatment of Acute Alcoholic Hepatitis

The article examines the influence of the Biologically Active Dietary Supplement (BADS) "Oleopren Hepa" as a hepatoprotective effect in the comprehensive treatment of acute alcoholic hepatitis. During the study, the authors obtained evidence of the effectiveness and functional orientation of the BADS. The materials for the research are the data obtained during the examination and treatment of 60 patients with acute alcoholic hepatitis. All examined patients were divided into 2 groups: 1st group (main), which received dietary supplements; the 2nd group (control) who did not receive this supplement. The average age of patients was 38.7 ± 9.3 years. The study was carried out based on the gastroenterological department of the city clinical hospital. As a result of the use of BADS in the comprehensive therapy of patients with acute alcoholic hepatitis, hepatomegaly was significantly reduced, and a decrease in the levels of total bilirubin, AsAt, AlAT, GGTP and cholesterol was observed. Additional intake of a specialized product enhanced the hepatoprotective effect of the main treatment. According to the tested biochemical parameters, the dynamics were better than in the control group. The use of the BADS, in addition to comprehensive therapy, increases the effectiveness of treatment of acute alcoholic hepatitis.

Selenoneine Ameliorates Hepatocellular Injury and Hepatic Steatosis in a Mouse Model of NAFLD.

Selenoneine is a novel organic selenium compound markedly found in the blood, muscles, and other tissues of fish. This study aimed to determine whether selenoneine attenuates hepatocellular injury and hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD). Mice lacking farnesoid X receptor (FXR) were used as a model for fatty liver disease, because they exhibited hepatomegaly, hepatic steatosis, and hepatic inflammation. Fxr-null mice were fed a 0.3 mg Se/kg selenoneine-containing diet for four months. Significant decreases in the levels of hepatomegaly, hepatic damage-associated diagnostic markers, hepatic triglycerides, and total bile acids were found in Fxr-null mice fed with a selenoneine-rich diet. Hepatic and blood clot total selenium concentrations were 1.7 and 1.9 times higher in the selenoneine group than in the control group. A marked accumulation of selenoneine was found in the liver and blood clot of the selenoneine group. The expression levels of oxidative stress-related genes (heme oxygenase 1 (Hmox1), glutathione S-transferase alpha 1 (Gsta1), and Gsta2), fatty acid synthetic genes (stearoyl CoA desaturase 1(Scd1) and acetyl-CoA carboxylase 1 (Acc1)), and selenoprotein (glutathione peroxidase 1 (Gpx1) and selenoprotein P (Selenop)) were significantly decreased in the selenoneine group. These results suggest that selenoneine attenuates hepatic steatosis and hepatocellular injury in an NAFLD mouse model.

Eicosapentaenoic acid-containing polar lipids from seaweed Susabinori (Pyropia yezoensis) alleviate hepatic steatosis in obese db/db mice.

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Because hepatic steatosis is an early pathogenesis of NAFLD, the discovery of food components that could ameliorate hepatic steatosis is of interest. Susabinori (Pyropia yezoensis) is recognized as one of the most delicious edible brown algae, and we prepared lipid component of susabinori (SNL), which is rich in eicosapentaenoic acid (EPA)-containing polar lipids. In this study, we tested whether feeding SNL to db/db mice protects them from developing obesity-induced hepatic steatosis. After four weeks of feeding, hepatomegaly, hepatic steatosis, and hepatic injury were markedly alleviated in SNL-fed db/db mice. These effects were partly attributable to the suppression of activities and mRNA expressions of lipogenic enzymes and enhanced levels of adiponectin due to the SNL diet. Additionally, mRNA expression of monocyte chemoattractant protein-1, an inflammatory chemokine, was markedly suppressed, and the mRNA levels of PPARδ, the anti-inflammatory transcription factor, were strongly enhanced in the livers of db/db mice by the SNL diet. We speculate that the development and progression of obesity-induced hepatic steatosis was prevented by the suppression of chronic inflammation due to the combination of bioactivities of EPA, phospholipids, and glycolipids in the SNL diet.

Retrospective study of the course, treatment and long-term follow-up of Kawasaki disease: a single-center experience from Poland.

Kawasaki disease (KD) is an acute, self-limited, systemic vasculitis and the most common cause of acquired coronary artery disease in pediatric population in the developed countries. It occurs mostly in Asian countries; however, due to better access to diagnostic and imaging tests, it is more frequently diagnosed among pediatric patients in Poland. The aim of this study was to describe the clinical course with special interest in cardiac involvement, treatment and follow-up of Polish patients with KD. It is a single-center retrospective study. Clinical features (including coronary involvement), laboratory results and treatment were evaluated. In our study group, we observed elevated levels of indicators of inflammation: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leukocytosis, platelet count, fibrinogen, D-dimer and ferritin. We also noticed changes in lipid profile and liver enzymes. Twenty-four patients were diagnosed with coronary artery abnormalities. Mean day of treatment equaled 9th day of the disease. Kawasaki disease should be suspected in all pediatric patients who have fever lasting 5 days, or more particularly those under 5 years of age. It is very important to apply treatment within the first 10 days of disease due to the high risk of cardiovascular complications. Each child should have echocardiography on admission, around 14th day of the disease, after 4-6 weeks from the onset of symptoms, as well as long-term observation at least once a year due to the fact that the inflammatory process and changes in the lipid profile increase the risk of atherosclerosis. Children with coronary aneurysms should undergo check-ups every 6 months.

Chelating effects of siderophore in reducing organ dysfunction caused by iron overload in ICR Mice

Background and Objectives@#Iron is an essential element that plays a vital role in a wide variety of cellular processes. But when present in excess concentration in organs, it may increase the risk for liver disease, heart failure, and diabetes. Recently, siderophores, which are iron-chelating agents produced by microorganisms, have attracted tremendous attention because of their strong binding and high selectivity to the ferric form of iron. Thus, the use of siderophore in sequestering excess iron in the body as a form of therapy is very attractive. This study determined the effects of commercially available siderophore in sequestering excess iron in organs such as liver, heart, and pancreas under excess iron conditions. @*Methodology@#First, iron-overload was induced by injecting iron dextran (20 mg) into male ICR mice for three consecutive days. The effects of iron to the liver, heart, and pancreas and the possible sequestration by siderophore were determined by scoring histological sections. The liver iron concentration was also assessed by atomic absorption spectroscopy (AAS).@*Results and Conclusion@#The study showed that iron-overloaded mice exhibited skin hyperpigmentation and hemosiderosis in liver, heart, and pancreas. Significant changes in the liver include hepatomegaly and development of tumor. Iron-overloaded mice had 2,935% increase in liver iron content compared to the salinetreated mice. However, when iron-overloaded mice were treated with either 100 µg or 200 µg siderophore, there was a 77% and 84% decrease in liver iron content, respectively. Moreover, the treatment of ironoverloaded mice with siderophore prevented the development of hemosiderosis, tumor, and structural changes in the tissues studied. The results showed that siderophore can effectively reduce excess iron and organ damage in iron-overloaded mice and can be potentially employed in chelation therapy of iron-overload diseases. Further studies on the possible mechanisms of siderophore aside from decreasing iron excess and lowering organ dysfunction are recommended.

Evaluation of Two Liver Treatment Strategies in a Mouse Model of Niemann-Pick-Disease Type C1.

Niemann-Pick-disease type C1 (NPC1) is an autosomal-recessive cholesterol-storage disorder. Besides other symptoms, NPC1 patients develop liver dysfunction and hepatosplenomegaly. The mechanisms of hepatomegaly and alterations of lipid metabolism-related genes in NPC1 disease are still poorly understood. Here, we used an NPC1 mouse model to study an additive hepatoprotective effect of a combination of 2-hydroxypropyl-ß-cyclodextrin (HPßCD), miglustat and allopregnanolone (combination therapy) with the previously established monotherapy using HPßCD. We examined transgene effects as well as treatment effects on liver morphology and hepatic lipid metabolism, focusing on hepatic cholesterol transporter genes. Livers of Npc1-/- mice showed hepatic cholesterol sequestration with consecutive liver injury, an increase of lipogenetic gene expression, e.g., HMG-CoA, a decrease of lipolytic gene expression, e.g., pparα and acox1, and a decrease of lipid transporter gene expression, e.g., acat1, abca1 and fatp2. Both, combination therapy and monotherapy, led to a reduction of hepatic lipids and an amelioration of NPC1 liver disease symptoms. Monotherapy effects were related to pparα- and acox1-associated lipolysis/ß-oxidation and to fatp2-induced fatty acid transport, whereas the combination therapy additionally increased the cholesterol transport via abca1 and apoE. However, HPßCD monotherapy additionally increased cholesterol synthesis as indicated by a marked increase of the HMG-CoA and srebp-2 mRNA expression, probably as a result of increased hepatocellular proliferation.

Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice.

Soybean oil consumption is increasing worldwide and parallels a rise in obesity. Rich in unsaturated fats, especially linoleic acid, soybean oil is assumed to be healthy, and yet it induces obesity, diabetes, insulin resistance, and fatty liver in mice. Here, we show that the genetically modified soybean oil Plenish, which came on the U.S. market in 2014 and is low in linoleic acid, induces less obesity than conventional soybean oil in C57BL/6 male mice. Proteomic analysis of the liver reveals global differences in hepatic proteins when comparing diets rich in the two soybean oils, coconut oil, and a low-fat diet. Metabolomic analysis of the liver and plasma shows a positive correlation between obesity and hepatic C18 oxylipin metabolites of omega-6 (ω6) and omega-3 (ω3) fatty acids (linoleic and α-linolenic acid, respectively) in the cytochrome P450/soluble epoxide hydrolase pathway. While Plenish induced less insulin resistance than conventional soybean oil, it resulted in hepatomegaly and liver dysfunction as did olive oil, which has a similar fatty acid composition. These results implicate a new class of compounds in diet-induced obesity-C18 epoxide and diol oxylipins.

Short-term vitamin E treatment impairs reactive oxygen species signaling required for adipose tissue expansion, resulting in fatty liver and insulin resistance in obese mice.

OBJECTIVES: The use of antioxidant therapy in the treatment of oxidative stress-related diseases such as cardiovascular disease, diabetes or obesity remains controversial. Our aim is to demonstrate that antioxidant supplementation may promote negative effects if used before the establishment of oxidative stress due to a reduced ROS generation under physiological levels, in a mice model of obesity. METHODS: C57BL/6J mice were fed with a high-fat diet for 14 weeks, with (OE group) or without (O group) vitamin E supplementation. RESULTS: O mice developed a mild degree of obesity, which was not enough to induce metabolic alterations or oxidative stress. These animals exhibited a healthy expansion of retroperitoneal white adipose tissue (rpWAT) and the liver showed no signs of lipotoxicity. Interestingly, despite achieving a similar body weight, OE mice were insulin resistant. In the rpWAT they presented a reduced generation of ROS, even below physiological levels (C: 1651.0 ± 212.0; O: 3113 ± 284.7; OE: 917.6 ±104.4 RFU/mg protein. C vs OE p< 0.01). ROS decay may impair their action as second messengers, which could account for the reduced adipocyte differentiation, lipid transport and adipogenesis compared to the O group. Together, these processes limited the expansion of this fat pad and as a consequence, lipid flux shifted towards the liver, causing steatosis and hepatomegaly, which may contribute to the marked insulin resistance. CONCLUSIONS: This study provides in vivo evidence for the role of ROS as second messengers in adipogenesis, lipid metabolism and insulin signaling. Reducing ROS generation below physiological levels when the oxidative process has not yet been established may be the cause of the controversial results obtained by antioxidant therapy.

Infant with hepatomegaly and hypoglycemia: A setting for fatty acid oxidation defects.

Fatty acid oxidation defects (FAOD) are one of the commonest metabolic liver diseases (MLDs) that can have varied presentations in different age groups. An infant presented with short history of jaundice and irritability, examination showed soft hepatomegaly. Investigations revealed non-ketotic hypoglycemia suggesting FAOD which was later confirmed as carnitine uptake defect with gas chromatography and mass spectrometry and mutation analysis. Patient improved with acute management of metabolic crisis, carnitine supplementation and corn starch therapy with reversal of encephalopathy, reduction in hepatomegaly, maintenance of euglycemia and improvement in liver function tests and creatine phosphokinase on follow up. Non-ketotic hypoglycemia is a characteristic finding in FAODs. Early diagnosis and appropriate management can result in excellent outcomes in patients with FAODs.

Biochemical mechanism underlying hypertriglyceridemia and hepatic steatosis/hepatomegaly induced by acute schisandrin B treatment in mice.

BACKGROUND: It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used traditional Chinese herb), increased serum and hepatic triglyceride (TG) levels and hepatic mass in mice. The present study aimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia, hepatic steatosis and hepatomegaly. METHODS: Male ICR mice were given a single oral dose of Sch B (0.25-2 g/kg). Sch B-induced changes in serum levels of biomarkers, such as TG, total cholesterol (TC), apolipoprotein B48 (ApoB 48), very-low-density lipoprotein (VLDL), non-esterified fatty acid (NEFA) and hepatic growth factor (HGF), as well as hepatic lipids and mass, epididymal adipose tissue (EAT) and adipocyte size, and histological changes of the liver and EAT were examined over a period of 12-120 h after Sch B treatment. RESULTS: Serum and hepatic TG levels were increased by 1.0-4.3 fold and 40-158% at 12-72 h and 12-96 h, respectively, after Sch B administration. Sch B treatment elevated serum ApoB 48 level (up to 12%), a marker of exogenous TG, but not VLDL, as compared with the vehicle treatment. Treatment with Sch B caused a time-/dose-dependent reduction in EAT index (up to 39%) and adipocyte size (up to 67%) and elevation in serum NEFA level (up to 55%). Sch B treatment induced hepatic steatosis in a time-/dose-dependent manner, as indicated by increases in total vacuole area (up to 3.2 fold vs. the vehicle control) and lipid positive staining area (up to 17.5 × 103 µm2) in liver tissue. Hepatic index and serum HGF levels were increased by 18-60% and 42-71% at 12-120 h and 24-72 h post-Sch B dosing, respectively. In addition, ultrastructural changes, such as increase in size and disruption of cristae, in hepatic mitochondria were observed in Sch B-treated mice. CONCLUSION: Our findings suggest that exogenous sources of TG and the breakdown of fat storage in the body contribute to Sch B-induced hypertriglyceridemia and hepatic steatosis in mice. Hepatomegaly (a probable hepatotoxic action) caused by Sch B may result from the fat accumulation and mitochondrial damage in liver tissue.

Primary Carnitine Deficiency - A Rare Treatable Cause of Cardiomyopathy and Massive Hepatomegaly.

Systemic primary carnitine deficiency (CDSP) is a rare autosomal recessive disorder caused by a defect in plasma membrane uptake of carnitine due to SLC22A5 gene mutations. A nine-mo-old boy presented with hypertrophic cardiomyopathy, massive hepatomegaly and jaundice. Metabolic testing revealed very low free carnitine levels. Genetic analysis using Sanger sequencing method revealed compound heterozygous mutations in SLC22A5 gene, c. 1354 G > A (p. Glu452Lys, previously reported) and c.231_234del (novel frame-shift). Oral carnitine supplementation resulted in improved clinical outcome with ejection fraction to 75 % and normalization of liver size and enzymes after 3 mo.

Carotenemia and hepatomegaly in an atopic child on an exclusion diet for a food allergy.

Eczema is a frequent childhood manifestation and a few atopic children are allergic to certain foods or aeroallergens. Anxious parents of atopic children often have a fear of topical steroid-related side-effects, and some may try a range of elimination diets to avoid allergies. Elimination diets increase the risk of anaphylaxis on re-exposure to previously tolerated foods from the loss of oral tolerance. Unbalanced diets together with an inadvertent excessive consumption of fruits and vegetables may lead to carotenemia from the carotenoids in the plant foods. Carotenemia is benign but unusual diets and the consumption of preformed vitamin A in health supplements can lead to vitamin A toxicity. We discuss a child with eczema on an exclusion diet presenting with anaphylaxis to dairy food. He had carotenemia with hepatomegaly, which resolved on dietary management.

Diagnostic performance of Contrast-enhanced CT in Pyrrolizidine Alkaloids-induced Hepatic Sinusoidal Obstructive Syndrome.

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. Since PAs exposure is obscure and clinical presentation of HSOS is unspecific, it is challenge to establish the diagnosis of PAs-induced HSOS. Gynura segetum is one of the most wide-use herbals containing PAs. The aim of our study is to describe the features of contrast-enhanced computed tomography (CT) in gynura segetum-induced HSOS, and then determine diagnostic performance of radiological signs. We retrospectively analyzed medical records and CT images of HSOS patients (71 cases) and the controls (222 cases) enrolled from January 1, 2008, to Oct 31, 2015. The common findings of contrast CT in PAs-induced HSOS included: ascites (100%), hepatomegaly (78.87%), gallbladder wall thickening (86.96%), pleural effusion (70.42%), hepatic vein narrowing (87.32%), patchy liver enhancement (92.96%), and heterogeneous hypoattenuation (100%); of these signs, patchy enhancement and heterogeneous hypoattenuation were valuable features. Then, the result of diagnostic performance demonstrated that contrast CT possessed better performance in diagnosing PAs-induced HSOS compared with various parameters of Seattle criteria. In conclusion, the patients with PAs-induced HSOS display distinct radiologic features at CT-scan, which reveals that contrast-enhanced CT provides an effective noninvasive method for diagnosing PAs-induced HSOS.