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- Protective Effect of Ethanolic Extract of Tabernaemontana divaricata (L.) R. Br. against DEN and Fe NTA Induced Liver Necrosis in Wistar Albino Rats. [Journal Article]
- Biomed Res Int 2014.:240243.
This study is an attempt to evaluate the hepatoprotective activity of Tabernaemontana divaricata against DEN and Fe NTA induced liver necrosis in rats. Ethanolic extract of the whole plant of Tabernaemontana divaricata at doses of 200 and 400 mg/kg body weight and 5-fluorouracil (standard drug) was orally administered to male Wistar Albino rats once daily for 24 weeks, simultaneously treated with the carcinogen DEN and Fe NTA. In simultaneously treated animals, the plant extract significantly decreased the levels of uric acid, bilirubin, AST, ALT, and ALP in serum and increased the levels of liver marker enzymes in liver. Treatment with the extracts resulted in a significant increase in the levels of antioxidants accompanied by a marked reduction in the levels of malondialdehyde when compared to DEN and Fe NTA treated group. When compared with 200 mg/kg bw rats, 400 mg/kg bw rats and 5-fluorouracil treated rats showed better results in all the parameters. The histopathological studies confirmed the protective effects of extract against DEN and Fe NTA induced liver necrosis. Thus, it could be concluded that the use of Tabernaemontana divaricata extract in the treatment of carcinogen induced hepatic necrosis.
- Chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine. [Journal Article]
- J Toxicol 2014.:583494.
Methamphetamine intoxication can cause acute hepatic failure. Chlorogenic and caftaric acids are the major dietary polyphenols present in various foods. The aim of this study was to evaluate the protective role of chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine in rats. Thirty-two male albino rats were divided into 4 equal groups. Group 1, which was control group, was injected (i.p) with saline (1 mL/kg) twice a day over seven-day period. Groups 2, 3, and 4 were injected (i.p) with methamphetamine (10 mg/kg) twice a day over seven-day period, where groups 3 and 4 were injected (i.p) with 60 mg/kg chlorogenic acid and 40 mg/kg caftaric acid, respectively, one day before methamphetamine injections. Methamphetamine increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, low-density lipoprotein, and triglycerides. Also, malondialdehyde in serum, liver, and brain and plasma and liver nitric oxide levels were increased while methamphetamine induced a significant decrease in serum total protein, albumin, globulin, albumin/globulin ratio, brain serotonin, norepinephrine and dopamine, blood and liver superoxide dismutase, and glutathione peroxidase levels. Chlorogenic and caftaric acids prior to methamphetamine injections restored all the above parameters to normal values. In conclusion, chlorogenic and caftaric acids before methamphetamine injections prevented liver toxicity and oxidative stress where chlorogenic acid was more effective.
- Bilateral simultaneous nonarteritic anterior ischemic optic neuropathy in a patient with alcoholic liver disease. [Journal Article]
- Oman J Ophthalmol 2014 May; 7(2):72-4.
A 53-year-old man with a history of alcoholism since 10 years admitted for jaundice elsewhere developed bilateral simultaneous decrease in vision in both the eyes 4 days after admission. His best-corrected visual acuity was 20/20 in both eyes. Visual field evaluation revealed an inferior altitudinal defect in both the eyes. Optic disc appearance, visual fields, and optical coherence tomography of discs were suggestive of nonarteritic anterior ischemic optic neuropathy (NAION) in both the eyes. Liver function tests revealed elevated serum bilirubin and hepatic enzymes. He was negative for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Abdominal ultrasound revealed no focal hepatic lesion, and carotid doppler revealed no arteriosclerosis. A diagnosis of bilateral ischemic optic neuropathy associated with alcoholic hepatitis was made. Bilateral simultaneous NAION has been previously reported in perioperative visual loss, HCV infection, and interferon treatment. This is the first case report of bilateral simultaneous NAION in alcoholic hepatitis in the absence of associated infective viral hepatitis. We explore the pathophysiology of ischemic optic neuropathy in liver disease. An early intervention to correct the risk factors leading to NAION may help in preventing this vision-threatening complication in patients with chronic liver disease.
- Serum lipid concentrations in patients with cholesterol and pigment gallstones. [JOURNAL ARTICLE]
- BMC Res Notes 2014 Aug 19; 7(1):548.
Gallstones (GS) are formed as a result of impaired metabolic regulation of the human body. Abnormal lipid metabolism is partly responsible for the pathogenesis of GS mainly rich in cholesterol. Thus abnormalities of serum lipids would reflect the possibilities of the formation of cholesterol GS. This study aims to identify the significance of serum lipids on the development of GS disease.Serum lipid profiles were estimated in 73 patients with symptomatic GS, admitted to the Teaching Hospital, Peradeniya, Sri Lanka for GS removal surgeries from May 2011 to December 2012. Patients with normal serum bilirubin level and not being on lipid lowering drugs were recruited for the study. Serum lipid profile of each patient was analyzed by enzymatic kit assays and the chemical composition of GS was analyzed by Fourier Transform Infrared spectroscopy.Of the 73 patients, 37 (51%) had cholesterol GS while 36 (49%) had pigment GS. Serum lipid parameters of a majority of patients were within the normal range. Body mass index values of the patients with two types of GS were not significantly different (Two sample t test, p = 0.335). Out of the lipid parameters tested, only serum triglyceride concentration was significantly high in patients with cholesterol GS than that of pigment GS (Two sample t test, p = 0.038). None of the lipid parameters were significantly different between males and females (Two sample t test, p > 0.05). Compared to the patients with pigment GS who were aged below 50 years, mean total cholesterol and triglyceride concentrations were higher in the same age category patients with cholesterol GS.Abnormal serum lipid profiles doesn't seem to be an essential feature in patients with cholesterol GS. However when the two groups of patients with cholesterol and pigment GS with no significant difference of body mass indexes were compared, patients with cholesterol GS are more likely to have serum lipid parameters towards the undesirable cutoff levels of their respective normal ranges. However an effect of serum lipid concentrations on high incidence of GS among females has not been identified.
- Bleeding outcome during a dengue outbreak in 2005 in the East-coast region of Peninsular Malaysia: a prospective study. [Journal Article]
- Trop Biomed 2014 Jun; 31(2):270-80.
During a dengue outbreak in 2005 in the East-coast region of Peninsular Malaysia, one of the worst hit areas in the country at that time, we undertook a prospective study. We aimed to describe the bleeding outcome and changes in the liver and hematologic profiles that were associated with major bleeding outcome during the outbreak. All suspected cases of dengue admitted into the only referral hospital in the region during the outbreak were screened for WHO 2002 criteria and serology. Liver function, hematologic profile and severity of bleeding outcome were carefully documented. The association between symptoms, liver and hematologic impairments with the type of dengue infection (classical vs. hemorrhagic) and bleeding outcome (major vs. non-major) was tested. Dengue fever was confirmed in 183 cases (12.5/100,000 population) and 144 cases were analysed. 59.7% were dengue hemorrhagic fever, 3.5% were dengue shock syndrome and there were 3 in-hospital deaths. Major bleeding outcome (gastrointestinal bleeding, intracranial bleeding or haemoptysis) was present in 14.6%. Elevated AST, ALT and bilirubin were associated with increasing severity of bleeding outcome (all P < 0.05). Platelet count and albumin level were inversely associated with increasing severity of bleeding outcome (both P < 0.001). With multivariable analysis, dengue hemorrhagic fever was more likely in the presence of abdominal pain (OR 1.1, 95% CI 0.02- 1.6) and elevated AST (OR 1.0, 95% CI 1.0-1.1) but the presence of pleural effusion (OR 5.8, 95% CI: 1.1-29.9) and elevated AST (OR 1.008, 95% CI: 1.005-1.01) predicted a severe bleeding outcome. As a conclusion, the common presence of a severe hemorrhagic form of dengue fever may explain the rising death toll in recent outbreaks and the worst impairment in liver and hematologic profiles was seen in major bleeding outcome.
- Human liver stem/progenitor cells decrease serum bilirubin in hyperbilirubinemic Gunn rat. [Journal Article]
- World J Gastroenterol 2014 Aug 14; 20(30):10553-63.
To test the ability of adult-derived human liver stem/progenitor cells (ADHLSC) from large scale cultures to conjugate bilirubin in vitro and in bilirubin conjugation deficient rat.ADHLSC from large scale cultures were tested for their phenotype and for their capacity to conjugate bilirubin in vitro after hepatogenic differentiation. In vivo, Gunn rats [uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) deficient animal] were injected with ADHLSC and cryopreserved hepatocytes (positive control). Two, 4, 13 and 27 wk post-transplantation, transplanted Gunn rat bilirubin serum levels were determined by high performance liquid chromatography. Human transplanted cell engraftment was assessed 27 wk post-transplantation using immunohistochemistry and RTqPCR.Large scale culture conditions do not modify ADHLSC phenotype, ADHLSC were able to specifically conjugate bilirubin. ADHLSC were intraportally injected into Gunn rats and blood UCB was measured at different times post-transplantation, infused-Gunn rats exhibited a metabolic effect 3 mo post-transplantation and maintained over a 6 mo period. ADHLSC engraftment into Gunn rat's liver was demonstrated by RTqPCR and immunohistochemistry against albumin and UGT1A1.ADHLSC from large scale cultures are efficient in conjugating bilirubin in vitro and in restoring a deficient metabolic function (reducing bilirubin level) in hyperbilirubinemic rats.
- Improved hydroxyurea effect with the use of text messaging in children with sickle cell anemia. [JOURNAL ARTICLE]
- Pediatr Blood Cancer 2014 Aug 17.
In children with sickle cell anemia (SCA), hydroxyurea reduces morbidity, but adherence is frequently suboptimal. Because most families of children with SCA have access to cellular telephone services, we assessed the impact of text messaged reminders as a tool to improve adherence to hydroxyurea.All patients <19 years of age with HbSS or HbSβ(0) thalassemia who were treated with hydroxyurea at a maximal tolerated dosage (MTD) at St. Jude Children's Research Hospital Comprehensive Pediatric Sickle Cell Program and who received automated text message reminders (SIMON®) were retrospectively identified. Laboratory parameters, hospitalizations, and medication possession ratios (MPR) prior to and after initiation of SIMON® were compared to assess the impact of SIMON®.Of the 97.3% of families with access to a cell phone, 91% elected to receive text message reminders. Among 55 children receiving hydroxyurea at MTD, laboratory parameters reflected waning medication compliance during the 12 months prior to SIMON®. Following initiation of SIMON®, children had higher mean corpuscular volumes, hemoglobin levels and fetal hemoglobin percentages and lower absolute reticulocyte counts and bilirubin levels, suggesting improved medication adherence. Hospitalizations were uncommon before and after SIMON®, and medication possession ratios (MPRs) were high before and after SIMON®, neither was significantly changed.SIMON® was feasible and improved hematologic parameters in children with SCA receiving hydroxyurea at a MTD. Future work will include extension of this technology to children with other chronic medical conditions who require daily use of medication. Pediatric Blood Cancer © 2014 Wiley Periodicals, Inc.
- Risk of Drug-induced Liver Injury from Tumor Necrosis Factor Antagonists. [JOURNAL ARTICLE]
- Clin Gastroenterol Hepatol 2014 Aug 14.
Antagonists of tumor necrosis factor (anti-TNF agents) can cause drug-induced liver injury (DILI), yet little is known about the level of risk.We identified cases of DILI caused by anti-TNF agents in Iceland, from 2009 through 2013 at the National University Hospital of Iceland (n=11). We collected data on total use of the drugs by patients with DILI, and outcomes, compared to patients who received anti-TNF agents but did not develop DILI (controls, n=22).Of the 11 cases of DILI identified (8 in women; mean age, 46 years), 9 cases were caused by infliximab. DILI developed in 1/120 patients who received infliximab, 1/270 who received adalimumab, and 1/430 who received etanercept. Most patients with infliximab-associated DILI developed this disorder after 4 infusions (n=6). Four patients had jaundice at diagnosis of DILI and 8 had hepatocellular liver injury. The mean peak level of alanine aminotransferase was 704 U/L, of aspartate aminotransferase was 503 U/L, of alkaline phosphatase was 261 U/L, and of bilirubin was 47μmol/L. Seven patients with DILI were tested for anti-nuclear antibodies before therapy with an anti-TNF agent; 3 had positive test results, compared with 5 of the 14 controls tested. At DILI diagnosis, 8/11 patients tested positive for anti-nuclear antibodies. Of liver biopsies collected from 5 patients with DILI, 3 showed signs of severe acute hepatitis. Only 9% of the patients who developed DILI received methotrexate during anti-TNF therapy, compared with 59% of controls (P=.009). DILI was treated with steroids in 5 patients; for 4 cases, steroid therapy was discontinued without relapse. Eight patients with DILI went on to receive treatment with different TNF antagonists without developing DILI.Of anti-TNF agents, infliximab is most frequently associated with DILI, developing in 1/120 patients who received this drug. Fifty percent of patients with anti-TNF-associated DILI required steroid therapy, but most did not need long-term treatment. Addition of methotrexate to anti-TNF therapy might reduce the risk of DILI.
- [Clinical application of blood matching with hemolgtic test in vitro for transfusion treatment of crisis puerpera with acute hemolytic anemia]. [English Abstract, Journal Article]
- Zhongguo Shi Yan Xue Ye Xue Za Zhi 2014 Jul; 22(4):1094-8.
This study was aimed to establish the matching method of hemolytic test in vitro, and to guide the transfusion treatment for puerpera with acute hemolytic disease. The donor's erythrocytes were sensibilized by all the antibodies in plasma of patient in vitro and were added with complement, after incubation for 6.5 hours at 38 °C, the hemolysis or no hemalysis were observed. It is safe to transfuse if the hemolysis did not occur. The results showed that when the matching difficulty happened to puerpera with acute hemolytic disease, the compatible donor could be screened by hemolytic test in vitro. There were no untoward effects after transfusion of 6 U leukocyte-depleted erythrocyte suspension. The all hemoglobin, total bilirubins, indirect bilirubin, reticulocyte, D-dimex and so on were rapidly improved in patient after transfusion , showing obvious clinical effecacy of treatment. It is concluded that when the matching results can not judge accuratly compatible or incompatible through the routine method of cross matching, the agglutinated and no-hemolytic erythrocytes can be screened by hemolytic test in vitro and can be transfused with good efficacy; the hemoglobin level can be promoted rapidly, and no untoward effects occur.
- Effect of interference from hemolysis, icterus and lipemia on routine pediatric clinical chemistry assays. [JOURNAL ARTICLE]
- Clin Chim Acta 2014 Aug 13.
Clinical laboratory assays can be affected by interferents like hemoglobin, (hb) lipids and bilirubin. We evaluated the effect of these interferences on pediatric samples for different chemistry assays. Further we established cut-off indices above which these interferences confound sample results.Three separate serum pools were spiked with increasing concentrations of hemolysate or Intralipid or bilirubin and different analytes were analyzed. The Hemolysis-(H), Lipemia-(T) and Icterus- (I) indices were measured on Vitros 5600. Analytes affected by lipemia were treated with LipoClear ® and re-analyzed. All the measured analytes were compromised by gross hemolysis (H-Index >1000).Except lipase and magnesium (Mg++), all other analytes were affected by moderate (H-Index >250) and significant hemolysis (H-Index >500). Low estradiol levels showed a significant effect at severe icterus (I-Index >20.0). C3, C4, Ceruloplasmin, Haptoglobin, Immunoglobulins (Ig) and Vitamin D were significantly affected by moderate (T-Index >100) and severe (T-Index >500) lipemia. LipoClear ® treatment significantly attenuated the lipemic interference on the above analytes except for C3, C4, and IgG.Accurate reporting of pediatric samples for the analytes affected by common interferences will lead to better clinical interpretation.