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- Altered frequencies of dendritic cells and IFN-c-secreting T cells with granulocyte colony-stimulating factor (G-CSF) therapy in acute-on- chronic liver failure. [Journal Article, Research Support, Non-U.S. Gov't]
- Liver Int 2014 Apr; 34(4):505-13.
Acute-on-chronic liver failure (ACLF) is a serious hepatic ailment with impaired immunity and poor treatment options resulting high mortality. Treatment with granulocyte colony-stimulating factor(G-CSF) mobilizes CD34(+) cells in ACLF patients; however its effect on impaired immune responses remains to be elucidated. To analyse the effect of G-CSF in immune modulation in ACLF.We have analysed the frequencies of circulating and intrahepatic myeloid (mDCs) and plasmacytoid(pDCs) dendritic cells (DCs) and T cells in ACLF patients treated with G-CSF (Group A; n = 23) and placebo (Group B; n = 24) using flow cytometry. IFN-c production was compared in both groups following stimulation of PBMCs with phorbol myristate acetate (PMA).In Group A, circulating and intrahepatic mDCs, pDCs (P < 0.04, P < 0.02) and T cells(CD3, CD4 and CD8) increased significantly post-G-CSF treatment in comparison to placebo group. Importantly in Group A, IFN-c-producing CD8 T cells were significantly decreased (P > 0.05) along with decreased serum bilirubin and international normalized ratio (INR). Intrahepatic DCs and IFN-clevel were compared in survivor and non-survivor. Non-survivors from both groups, showed decreased DCs, high IFN-c level and no improvement in clinical parameters including s-bilirubin and INR.G-CSF therapy increased the frequencies of dendritic cells and reduced IFN-c secreting CD8 T cells with improved clinical severity indices. Decreased IFN- c production may contribute to reduced hepatocellular damage in ACLF patients.Our observations support the basis for further use of G-CSF therapy as immune modulator in these patients.
- Elevated serum level of carbohydrate antigen 19-9 in benign biliary stricture diseases can reduce its value as a tumor marker. [Journal Article]
- Int J Clin Exp Med 2014; 7(3):744-50.
Although carbohydrate antigen (CA19-9) level is frequently upregulated in pancreatobiliary cancer, it is also elevated in some benign diseases. This study aimed to determine whether CA19-9 levels could be used to distinguish between benign obstructive jaundice and pancreatobiliary cancer. Fifty-seven patients with obstructive jaundice were studied retrospectively. Endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy, stone extraction, or stent placement were used to treat patients with benign bile duct stricture or inoperable malignant biliopancreatic diseases, whilst surgery was performed in suitable cases. Serum CA19-9 levels and some additional biochemical parameters were evaluated before and after treatment. CA19-9 levels were elevated in most patients, along with levels of total bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT), and 10 patients with benign disorders had extraordinarily high levels of these markers (> 1000 U/mL). The mean CA19-9 level in the malignant group was greater than that in the benign group (826.83 ± 557.34 vs. 401.92 ± 483.92 U/mL, P = 0.005), and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CA19-9 were 100%, 7.69%, 33.33% and 47.47%, respectively. CA19-9 levels in the whole cohort were correlated with ALP (r = 0.77, P < 0.001), GGT (r = 0.83, P < 0.001), bilirubin (r = 0.69, P < 0.001), and CRP (r = 0.37, P = 0.004). The reduction in serum level of CA19-9 after treatment in the malignant group was remarkably less than that observed in the benign group (97.26 ± 123.24 U/mL vs. 352.71 ± 397.29 U/mL, P < 0.001). CA19-9 levels may not be sufficient to distinguish between malignant and benign obstructive jaundice diseases.
- Asymmetric dimethylarginine levels in children with β-thalassemia and their correlations to tricuspid regurgitant jet velocity. [JOURNAL ARTICLE]
- Pediatr Blood Cancer 2014 Apr 21.
Pulmonary hypertension (PHT) may be the leading cause of death in β-thalassemia patients; however, its pathophysiologic mechanisms are still unclear. Recent studies indicate that asymmetric dimethylarginine (ADMA) plays a role in the initiation and progression of a variety of diseases, especially the cardiovascular system. The aim of this study is to assess the levels of ADMA in children with β-thalassemia and their correlations with tricuspid regurgitant jet velocity.This study was carried out on 30 children with β-thalassemia major and 30 healthy children served as a control group. Both groups underwent the following investigations: Blood sampling for CBC, LDH, serum ferritin, reticulocytic count, serum bilirubin, AST, ALT, in addition to plasma levels of ADMA. Doppler echocardiography was done for thalassemic group. Patients with tricuspid regurgitant jet velocity (TRV ≥ 2.5 m/sec) were considered risky for PHT.Plasma ADMA levels were significantly higher in patients with β-thalassemia than control group with a mean value 0.91 ± 0.14 and 0.62 ± 0.10 µmol/L respectively (P = 0.001). There was a significant positive correlation between plasma ADMA levels and tricuspid regurgitant jet velocity. The prevalence of elevated tricuspid regurgitant jet velocity (TRV ≥ 2.5 m/sec) in patients with thalassemia was 33.3%, with a significant increase of elevated TVR (≥2.5 m/sec) in patients with thalassemia with splenectomy than in patients without splenectomy.High plasma ADMA levels may be implicated in the pathogenesis of PHT in children with β-thalassemia. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
- Selective and sensitive detection of free bilirubin in blood serum using human serum albumin stabilized gold nanoclusters as fluorometric and colorimetric probe. [JOURNAL ARTICLE]
- Biosens Bioelectron 2014 Apr 8.:370-376.
We report here a fluorescence quenching based non-enzymatic method for sensitive and reliable detection of free bilirubin in blood serum samples using human serum albumin (HSA) stabilized gold nanoclusters (HSA-AuNCs) as fluorescent probe. The fluorescence of the nanoclusters was strongly quenched by bilirubin in a concentration dependent manner by virtue of the inherent specific interaction between bilirubin and HSA. A strong binding constant of 0.55×10(6)Lmole(-1) between the HSA-AuNC and bilirubin was discerned. The nano clusters each with size ~1.0nm (in diameter) and a core of Au18 were homogeneously distributed in HSA molecules as revealed from the respective high resolution transmission electron microscopic and mass spectroscopic studies. The fluorescence quenching phenomena which obeyed a simple static quenching mechanism, was utilized for interference free detection of bilirubin with minimum detection limit (DL) of 248±12nM (S/N=3). The fluorescence response of HSA-AuNCs against bilirubin was practically unaltered over a wide pH (6-9) and temperature (25-50°C) range. Additionally, peroxidase-like catalytic activity of these nanoclusters was exploited for colorimetric detection of bilirubin in serum sample with a DL of 200±19nM by following the decrease in absorbance (at λ440nm) of the reaction and its rate constant (Kp) of 2.57±0.63mLμg(-1)min(-1). Both these fluorometric and colorimetric methods have been successfully used for detection of free bilirubin in blood serum samples.
- The Potential Effect of Berberine in Mercury-induced Hepatorenal Toxicity in Albino Rats. [JOURNAL ARTICLE]
- Food Chem Toxicol 2014 Apr 18.
Mercury (Hg) is the third most dangerous heavy metal after arsenic and lead. Mercury's toxicity brings serious risks to health through negative pathological and biochemical effects. The study was designed to investigate the possible protective role of berberine (BN) in mercuric chloride (HgCl2) induced oxidative stress in hepatic and renal tissues. Adult male albino Wistar rats were exposed to mercuric chloride (HgCl2; 0.4 mg/kg bwt) for 7 days. Treatment with HgCl2 induced oxidative stress by increasing lipid peroxidation and nitric oxide production along with a concomitant decrease in glutathione and various antioxidant enzymes, namely superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. HgCl2 intoxication increased the activities of liver enzymes and the bilirubin level, in addition to the levels of urea and creatinine in serum. BN (100 mg/kg bwt) treatment inhibited lipid peroxidation and nitric oxide production, whereas it increased glutathione content. Activities of antioxidants enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, were also restored concomitantly when compared to control after BN administration. BN also inhibited the apoptotic effect of HgCl2 by increasing the expression of Bcl-2 protein in liver and kidney. Histopathological examination of the liver and kidney tissues proved the protective effect of BN against HgCl2 toxicity. These results demonstrated that BN augments antioxidant defense against HgCl2-induced toxicity and provides evidence that it has therapeutic potential as hepato- and reno-protective agent.
- Transthoracic Echocardiography and 6-Minute Walk Test in Kuwaiti Sickle Cell Disease Patients. [JOURNAL ARTICLE]
- Med Princ Pract 2014 Apr 17.:212-217.
Objective: The aim of this study was to investigate cardiac abnormalities in Kuwaiti sickle cell disease (SCD) patients using markers such as tricuspid regurgitant jet velocity (TRJV), pulmonary artery systolic pressure (PASP), and the 6-minute walk (6MW) test and correlate these findings with clinical, hematological, and biochemical parameters. Materials and Methods: Seventy-three patients with SCD and 70 matched controls were studied. The cardiac status was investigated using transthoracic echocardiography in 57 patients; the 6MW test was carried out in patients and controls. Complete blood counts and hemolytic parameters were assessed. Results: Reticulocytes, bilirubin, and lactate dehydrogenase were significantly higher (p < 0.0001) in patients, while hemoglobin (Hb) and haptoglobin were lower (p < 0.0001) than in controls. The mean fetal Hb among patients was 15.85 ± 8.7%. Of the 57 patients, 14 (24.5%) and 15 (26%) had mild tricuspid and mitral regurgitation, respectively. The mean ejection fraction, TRJV, and PASP were 63.9 ± 6.3%, 1.7 ± 0.5 m/s, and 23.0 ± 7.3 mm Hg, respectively. Three (5.2%) patients had mildly raised TRJV (2.6-2.97 m/s, normal range <2.5 m/s) while 8 (14%) had high PASP (mean 35.3 ± 5.1 mm Hg, normal range <30 mm Hg). Hb, hematocrit, and reticulocytes were different (p = 0.010, p = 0.006, and p = 0.011, respectively) between patients with normal and high PASP. All 3 patients who had a high TRJV had a high PASP, and 2 of these patients died during follow-up. The systolic and diastolic blood pressure, oxygen saturation before and after the 6MW test, and distance walked were lower (p = 0.006, p = 0.000, p = 0.002, p = 0.000, and p = 0.000, respectively) in patients compared to controls. Conclusion: Raised PASP was common in Kuwaiti SCD patients while raised TRJV was not. © 2014 S. Karger AG, Basel.
- [Effect of emodin on expression of farnesoid X receptor in rats with acute cholestatic hepatitis]. [English Abstract, Journal Article]
- Zhongguo Dang Dai Er Ke Za Zhi 2014 Apr; 16(4):424-9.
To investigate the expression of farnesoid X receptor (FXR) and the effect of emodin on FXR expression in a rat model of acute cholestatic hepatitis.Ninety adult Sprague-Dawley rats were randomly divided into normal control, model, and emodin groups (n=30 each). The model and emodin groups were given alpha-naphthylisothiocyanate (ANIT) 50 mg/kg by gavage to establish an animal model of cholestatic hepatitis, while the normal control group was given an equal volume of sesame oil. The emodin group was given emodin by gavage every day from 4 days before the model was prepared until the time of sacrifice, while the model and normal control groups were given an equal volume of sodium carboxymethyl cellulose solution. At 24, 48 and 72 hours after the model was prepared, serum level of total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), and total bile acids (TBA) were measured by Aeroset automatic biochemical analyzer, and the mRNA expression of FXR in the liver tissue was measured by real-time PCR.At all time points FXR mRNA expression in the model group decreased, but serum levels of TB, DB, ALT and TBA increased significantly compared with the normal control group (P<0.05). The emodin group had significantly higher mRNA expression of FXR and significantly lower serum levels of TB, DB, ALT, and TBA compared with the model group (P<0.05).Emodin can significantly reduce serum levels of TB, DB, ALT, and TBA in rats with ANIT-induced cholestatic hepatitis, probably by promoting FXR expression.
- Neutrophil-lymphocyte ratio: a novel predictor for short-term prognosis in acute-on-chronic hepatitis B liver failure. [JOURNAL ARTICLE]
- J Viral Hepat 2013 Aug 28.
Acute-on-chronic hepatitis B liver failure (ACHBLF) has a poor prognosis in patients with hepatitis B virus infection. The role of the neutrophil-lymphocyte ratio (NLR), which reflects the inflammatory status of the patient before treatment, has never been studied in this setting. To investigate the predictive value of NLR in patients with ACHBLF, a retrospective cohort with 216 patients and a prospective validation cohort with 73 patients were recruited. Multivariate analyses showed that total bilirubin (TBIL), NLR, age and model for end-stage liver disease (MELD) score had prognostic significance for survival. Both NLR (0.781) and MELD score (0.744) had higher ROC curves, which differed significantly from those for age (0.615) and TBIL (0.691), but not from each other (P = 0.94). NLR ≤2.36 predicted lower mortality (with 91.6% sensitivity and 86.0% negative predictive value), and NLR >6.12 was a warning sign for higher mortality risk (with 90.1% specificity and 80.3% positive predictive value). These results demonstrated that pretreatment NLR was associated with the prognosis of patients with ACHBLF, and elevated NLR predicted poor outcome within 8 weeks. We suggest that NLR cut-offs of ≤2.36 and >6.12 are powerful markers for predicting mortality in ACHBLF.
- Fifteen-Year Experience and Outcomes of Pericardiectomy for Constrictive Pericarditis. [JOURNAL ARTICLE]
- J Card Surg 2014 Apr 18.
Constrictive pericarditis has multiple etiologies and can lead to disabling symptoms and severe heart failure with poor quality of life. Surgical pericardiectomy is the cornerstone of management. All patients undergoing pericardiectomy at our institution were reviewed with the goal of analyzing preoperative and intraoperative factors that may be associated with long-term outcomes.A retrospective review of our cardiac surgery database identified all patients who underwent pericardiectomy for constrictive pericarditis between 1997 and 2012. Demographic, comorbidity, operative, and outcome data were analyzed.Thirty-six patients underwent pericardiectomy for constrictive pericarditis over 15 years. Etiologies included idiopathic (n = 20, 55.6%), postoperative (n = 11, 30.5%), postradiation (n = 3, 8.3%), and tuberculosis (n = 2, 5.6%). Total pericardiectomy was performed in 35 patients. The average preoperative cardiac index was 2.6 L/min/m(2) with a significant increase to 3.1 L/min/m(2) noted in the immediate postoperative period (p = 0.03). There were no perioperative mortalities. The 1-year, 5-year, 10-year, and 15-year survival rates were 97.2%, 94.6%, 86.5%, and 78.3%, respectively. On multivariate analysis, preoperative heart failure (hazard ratio 2.2, p = 0.06), elevated preoperative total bilirubin (>2.7 mg/dL, hazard ratio 6.8, p = 0.02), and elevated creatinine (>1.4 mg/dL, hazard ratio 3.1, p = 0.05) were risk factors for increased long-term mortality. Kaplan-Meier survival analysis showed a significant decrease in overall survival associated with postradiation etiology (p = 0.05).Pericardiectomy can be performed with low mortality and immediate improvement in hemodynamics. Those patients with compromised cardiac output, abnormal hepatic or renal function, or with previous radiation therapy have reduced long-term survival.
- Molecular Analysis of the UGT1A1 Gene in Korean Patients with Crigler-Najjar Syndrome Type II. [Journal Article]
- Pediatr Gastroenterol Hepatol Nutr 2014 Mar; 17(1):37-40.
Crigler-Najjar syndrome type II (CN-2) is characterized by moderate non-hemolytic unconjugated hyperbilirubinemia as a result of severe deficiency of bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1). The study investigated the mutation spectrum of UGT1A1 gene in Korean children with CN-2.Five Korean CN-2 patients from five unrelated families and 50 healthy controls were enrolled. All five exons and flanking introns of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and the PCR products were directly sequenced.All children initially presented with neonatal jaundice and had persistent indirect hyperbilirubinemia. Homozygous p.Y486D was identified in all five patients. Three patients had an associated homozygous p.G71R and two a heterozygous p.G71R. The allele frequency of p.Y486D and p.G71R in healthy controls was 0 and 0.16, respectively. No significant difference in mean serum bilirubin levels was found between homozygous carriers of p.G71R and heterozygous carriers.The combination of homozygous p.Y486D and homozygous or heterozygous p.G71R is identified. The p.Y486D and p.G71R can be screened for the mutation analysis of UGT1A1 in Korean CN-2 patients.