Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Early termination of immune tolerance state of hepatitis B virus infection explains liver damage. [Journal Article]
- World J Hepatol 2014 Aug 27; 6(8):621-5.
To assess an early termination of immune tolerance state of chronic hepatitis B virus infection in Bangladesh and its clinical significance.From a series of 167 treatment-naive chronic hepatitis B patients aged between 12 to 20 years (mean ± SD; 17.5 ± 2.8 years), percutaneous liver biopsies of 89 patients who were all hepatitis B e antigen negative at presentation were done. Of them, 81 were included in the study. They had persistently normal or raised serum alanine aminotransferase (ALT) values. A precore mutation (PCM) study was accomplished in 8 patients who were randomly selected.Forty-four (53.7%) patients had significant necroinflammation (HAI-NI > 7), while significant fibrosis (HAI-F ≥ 3) was seen in 15 (18.5%) patients. Serum ALT (cut off 42 U/L) was raised in 29 (35.8%) patients, while low HBV DNA load (< 10(5) copies/mL) was observed in 57 (70.4%) patients. PCM was negative in all 8 patients.This study indicates that the current concept of age-related immune tolerance state of HBV infection deserves further analyses in different population groups.
- Practical approach in hepatitis B e antigen-negative individuals to identify treatment candidates. [REVIEW]
- World J Gastroenterol 2014 Sep 14; 20(34):12045-12055.
The natural history of chronic hepatitis B is characterized by different phases of infection, and patients may evolve from one phase to another or may revert to a previous phase. The hepatitis B e antigen (HBeAg)-negative form is the predominant infection worldwide, which consists of individuals with a range of viral replication and liver disease severity. Although alanine transaminase (ALT) remains the most accessible test available to clinicians for monitoring the liver disease status, further evaluations are required for some patients to assess if treatment is warranted. Guidance from practice guidelines together with thorough investigations and classifications of patients ensure recognition of who needs which level of care. This article aims to assist physicians in the assessment of HBeAg-negative individuals using liver biopsy or non-invasive tools such as hepatitis B s antigen quantification and transient elastography in addition to ALT and hepatitis B virus DNA, to identify who will remain stable, who will reactivate or at risk of disease progression hence will benefit from timely initiation of anti-viral therapy.
- Pharmacodynamic interaction of Spirulina platensis and deltamethrin in freshwater fish Nile tilapia, Oreochromis niloticus: impact on lipid peroxidation and oxidative stress. [JOURNAL ARTICLE]
- Environ Sci Pollut Res Int 2014 Sep 19.
Spirulina platensis (SP) is one of the most commonly used dietary supplements in human and many animal species, including fish. Recently, it has gained more attention in fish not only for its growth-promoting and immunomodulatory effects but also for its antioxidant potential. The present study was conducted to investigate the protective role of two different dietary levels of SP on freshwater Nile tilapia; Oreochromis niloticus exposed to subacute deltamethrin (DLM) intoxication. Spirulina was supplemented at levels of 0.5 and 1 % in the diet along with DLM at a concentration of 1.46 μg/l for 28 days. Serum biochemical parameters, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein, albumin, cholesterol, urea, uric acid and creatinine, were estimated. In addition, the level of malondialdehyde (MDA) was analysed as a lipid peroxidation marker. Reduced glutathione (GSH) content and glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activities were analysed as antioxidant biomarkers in liver, kidney and gills. The results revealed that DLM intoxication increased serum AST, ALT, ALP, cholesterol, urea, uric acid, creatinine and tissue MDA, while decreased serum total protein and albumin as well as tissue GSH level and GSH-Px, SOD and CAT activities. SP supplementation at the two tested levels enhanced all altered serum biochemical parameters as well as tissue lipid peroxidation and antioxidant biomarkers. Therefore, it could be concluded that SP administration could minimize DLM-induced toxic effects by its free radical scavenging and potent antioxidant activity.
- Circulating progranulin level is associated with visceral fat and elevated liver enzymes: Significance of serum progranulin as a useful marker for liver dysfunction. [JOURNAL ARTICLE]
- Endocr J 2014 Sep 17.
Progranulin was recently identified as one of the adipokines involved in the development of insulin resistance. Thus, the aim of this study was to explore the importance of progranulin as a novel marker for metabolic diseases in Japanese. A total of 138 subjects were recruited by the Aijinkai Total Health Care Center. Physical examination, blood sample examination and total body CT scan were performed for all participants. Serum progranulin levels were examined in subjects with or without metabolic syndrome and with or without liver enzyme elevation. Association study of serum progranulin levels and regression analysis of the relationship of elevated liver enzymes to representative metabolic parameters were performed. The metabolic syndrome group exhibited older age, and higher BMI, blood pressure, fasting glucose, HbA1c, IRI, HOMA-R, TG, FFA, CRP, AST, ALT, LDH, and ALP, and larger visceral fat area, subcutaneous fat area and visceral fat area/subcutaneous fat area. Serum progranulin concentrations were significantly higher in the metabolic syndrome group than in the non-metabolic syndrome group. Bivariate correlation analysis revealed that serum progranulin concentrations correlated positively and significantly with AST, ALT, LDH, γGTP, ALP, waist circumference and visceral fat area. The group with elevated liver enzymes exhibited higher BMI, blood pressure, IRI, HOMA-R, and progranulin level and larger waist circumference and visceral fat area than the group without them. In logistic regression analysis, visceral fat area and progranulin were significantly predictive of elevated liver enzymes. These results suggest that serum progranulin level as well as visceral fat are associated closely with liver dysfunction.
- Genetic analysis of diffuse high-grade astrocytomas in infancy defines a novel molecular entity. [JOURNAL ARTICLE]
- Brain Pathol 2014 Sep 18.
Paediatric high-grade gliomas are considered to be different when compared to adult high-grade gliomas in their pathogenesis and biological behaviour. Recently, common genetic alterations including mutations in the H3F3A/ATRX/DAXX pathway have been described in approximately 30 % of the paediatric cases. However, only few cases of infant high-grade gliomas have been analysed so far. We investigated the molecular features of 35 infants with diffuse high-grade astrocytomas, including 8 anaplastic astrocytomas (WHO grade III) and 27 glioblastomas (WHO grade IV) by immunohistochemistry, Multiplex Ligation Probe-dependent Amplification (MLPA), pyro-sequencing of glioma-associated genes and molecular inversion probe (MIP) assay. MIP and MLPA analyses showed that chromosomal alterations are significantly less frequent in infants compared to high-grade gliomas in older children and adults. We only identified H3F3A K27M in 2/34 cases (5.9 %), with both tumours located in the posterior fossa. PDGFRA amplifications were absent, and CDKN2A loss could be observed only in 2 cases. Conversely, 1q gain (22.7%) and 6q loss (18.2%) were identified in a subgroup of tumours. Loss of SNORD located on chromosome 14q32 was observed in 27.3% of the infant tumours, a focal copy number change not previously described in gliomas. Our findings indicate that infant high-grade gliomas appear to represent a distinct genetic entity suggesting a different pathogenesis and biological behaviour.
- Leiomyosarcoma With Alternative Lengthening of Telomeres Is Associated With Aggressive Histologic Features, Loss of ATRX Expression, and Poor Clinical Outcome. [JOURNAL ARTICLE]
- Am J Surg Pathol 2014 Sep 16.
Leiomyosarcoma is an aggressive soft tissue sarcoma with poor patient survival. Recently, it was shown that 53% to 62% of leiomyosarcomas use the alternative lengthening of telomeres (ALT) as their telomere maintenance mechanism. The molecular basis of this mechanism has not been elucidated. Studies of pancreatic neuroendocrine tumor have suggested that the inactivation of either α-thalassemia/mental retardation syndrome X-linked (ATRX) or death domain-associated (DAXX) protein is associated with the ALT phenotype. In this study, we sought to determine the clinicopathologic features of leiomyosarcoma with the ALT phenotype and the possible relationship between this phenotype and ATRX/DAXX expression. Telomerase reverse transcriptase gene (TERT) promoter mutation analysis was also performed. Ninety-two leiomyosarcomas derived from the uterus, retroperitoneum/intra-abdomen, and various other sites were analyzed. Telomere-specific fluorescence in situ hybridization revealed that 59% (51/86) of leiomyosarcomas had the ALT phenotype. Loss of ATRX expression was observed in 33% of the tumors (30/92), and all but 2 ATRX-deficient tumors were ALT positive. Both the ALT phenotype and loss of ATRX expression were associated with epithelioid/pleomorphic cell morphology, tumor necrosis, and poor differentiation. None of the 92 cases lost DAXX expression. No TERT promoter mutation was detected (n=39). For survival analysis, poor differentiation, high FNCLCC grade, tumor size, and ALT phenotype were correlated with poor overall survival in univariate analysis. Tumor size and ALT phenotype remained independent prognostic factors in multivariate analysis. We concluded that the ALT phenotype in the leiomyosarcoma is associated with aggressive histologic features, loss of ATRX expression, and poor clinical outcome.
- Emodin Ameliorates Ethanol-Induced Fatty Liver Injury in Mice. [JOURNAL ARTICLE]
- Pharmacology 2014 Sep 12; 94(1-2):71-77.
The liver plays a central role in ethanol (EtOH) metabolism, and oxidative stress is implicated in alcohol-mediated liver injury. The present study aimed to investigate the role of emodin in EtOH-induced fatty liver injury. Liver histology, biochemistry and gene-expression studies were performed. Mice fed with an EtOH-containing diet exhibited severe macrovesicular steatosis and higher serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. However, emodin ameliorated liver steatosis and lowered ALT and AST. Emodin also decreased hepatic triglyceride in mice fed with EtOH. In addition, emodin attenuates Oil Red O staining in alcoholic fatty liver in mice. Hepatic cytochrome P450 2E1 protein levels were upregulated in EtOH-fed mice, but downregulated in emodin-treated mice. In addition, emodin decreased hepatic oxidative stress. Furthermore, emodin significantly reduced liver α-smooth muscle actin and collagen type I, whereas it increased the mRNA levels of PPAR-γ. Taken together, emodin plays protective roles in alcohol-mediated liver steatosis. © 2014 S. Karger AG, Basel.
- DPP-4 Inhibitors Improve Liver Dysfunction in Type 2 Diabetes Mellitus. [Journal Article]
- Med Sci Monit 2014.:1662-7.
Background Dipeptidyl peptidase-4 (DPP-4) inhibitors might have pleiotropic effects because receptors for incretin exist in various tissues, including liver. We examined whether DPP-4 inhibitors affect liver function in patients with type 2 diabetes. Material and Methods A retrospective review of 459 patients with type 2 diabetes who were prescribed DPP-4 inhibitors was performed. After exclusion of patients with hepatitis B or C, steroid use, and other diseases that might affect liver function and diabetes status, 224 patients were included in the analysis. Results Forty-four patients (19.6%) with liver injury defined by aspartate transaminase (AST) or alanine transaminase (ALT) over the normal level of 40 U/L. In the patients with liver injury, AST and ALT were significantly decreased after 6 months from the first date of DPP-4 prescription, with mean changes of -6.2 U/L [95% confidence interval (CI) -10.9 to -1.4, p=0.012] and of -11.9 U/L (95%CI -19.5 to -4.2, p=0.003), respectively. Percent changes in AST were significantly and negatively correlated with baseline AST and ALT (r=-0.27, p<0.001 and r=-0.23, p=0.002, respectively), and percent changes in ALT were also negatively correlated with them (r=-0.23, p=0.001 and r=-0.27, p<0.001, respectively). Conclusions DPP-4 inhibitors improved liver dysfunction in patients with type 2 diabetes.
- Pu-erh Tea Powder Preventive Effects on Cisplatin-Induced Liver Oxidative Damage in Wistar Rats. [Journal Article]
- Asian Pac J Cancer Prev 2014; 15(17):7389-94.
Chemotherapy is one of the major means for control of malignancies, with cisplatin (CDDP) as one of the main agents, widely used for the treatment of various malignant solid tumors. However, prevention of hepatotoxicity from cisplatin is one of the urgent issues in cancer chemotherapy. In this study, we aimed to investigate the effects of pu-erh tea on hepatotoxicity through body weight and tissue antioxidant parameters like, liver coefficient, serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde(MDA) and glutathione (GSH) levels, and light microscopic evaluation by histological findings.The rats were randomly divided into five groups: Control (n=10), cisplatin (3 mg/kg p.i., n=10), cisplatin+pu-erh (0.32 g/kg/day i.g., n=10), cisplatin+pu-erh (0.8 g/kg/day i.g., n=10) and cisplatin+pu-erh (1.6 g/kg/day i.g., n=10). Pu-erh tea powder was administrated for 31 consecutive days. The rats were sacrificed at the end on the second day after a single dose of cisplatin treatment for measuring indices.Pu-erh tea powder exhibited a protective effect by decreasing MDA and GSH and increasing the SOD and GSH-PX levels and GSH-PX/MDA ratio in camparison with the control group. Besides, pu-erh tea was also able to alleviate the pathological damage to some extent.Pu-erh tea powder is protective against cisplatin-induced liver oxidative damages, especially at the medium dosage (0.8 g/kg/d).
- IL28B rs12979860 Gene Polymorphism in Egyptian Patients with Chronic Liver Disease Infected with HCV. [Journal Article]
- Asian Pac J Cancer Prev 2014; 15(17):7213-8.
Egypt has one of the highest prevalences of hepatitis C virus (HCV) infection worldwide. Although the IL28B gene polymorphism has been shown to modify the course of chronic HCV infection, this has not been properly assessed in the Egyptian population.The IL28B rs12979860 single nucleotide polymorphism (SNP) was therefore examined in 256 HCV-infected Egyptian patients (group II) at different stages of disease progression and in 48 healthy volunteers (group I). Group II was subdivided into GII-A (chronic hepatitis patients, n=119), GII-B (post hepatitis cirrhosis, n=66) and GII-C (HCC on top of cirrhosis, n=71).The C/T genotype was the commonest in all groups. It was more frequent in GI (52%) than in GII (48%). There was no significant difference in the frequency of C/T and C/C or T/T genotypes between groups and subgroups (p=0.82). Within the subgroups; the C/C genotype was more common in GII-B while C/T and T/T genotypes were more common in GII-C, though with no significant difference (p=0.59 and p=0.80). There was no significant association between IL28B rs12979860 SNP and viral load, ALT, AFP level, METAVIR scores for necro-inflammation and fibrosis, and Child-Pugh classification.1) IL28Brs12979860 C/T genotype is the commonest genotype in HCV-associated CH and HCC in Egypt. 2) IL28Brs12979860 polymorphisms are not associated with disease progression or aggression (histological staging, severity of fibrosis in CH or the incidence of post-HCV HCC). 3) Differences in IL28Brs12979860 genotypes could be a consequence of environmental or ethnic variation.