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1.
Indian J Med Microbiol ; 47: 100530, 2024.
Article in English | MEDLINE | ID: mdl-38246242

ABSTRACT

PURPOSE: The choice of antibiotics for treatment of Carbapenem-Resistant Enterobacterales (CRE) is increasing becoming limited due to co-expression of Metallo-beta-lactamases (MBL) along with other carbapenemases in these isolates. The study aimed to investigate the occurrence of CRE and to determine the in-vitro synergy and clinical outcomes of Ceftazidime-Avibactam and Aztreonam combination in CRE infections in adult Intensive Care Units (ICUs). METHODS: 79 CRE isolates recovered from adult ICUs during January to March 2023 were tested by O.K.N.V.I. RESIST-5, a lateral flow multiplex assay for rapid detection of OXA-48-like, NDM, IMP, VIM, and KPC carbapenemases. Ceftazidime-Avibactam MIC was determined by microbroth dilution method and in vitro synergy between Ceftazidime-Avibactam and Aztreonam was assessed by Modified E-test/disc diffusion method for these isolates. RESULTS: The study revealed 7.5 % occurrence of CRE in our hospital, with high occurrence of NDM (n = 42, 53.1 %) and OXA-48-like (n = 63, 79.7 %) carbapenemase. Production of more than one type of carbapenemases was found in 44 isolates. A total of 57 isolates (72 %) had Ceftazidime-Avibactam resistance and 44 of them displayed Ceftazidime-Avibactam and Aztreonam in-vitro synergy. Successful clinical outcome was observed in two patients who received Ceftazidime-Avibactam and Aztreonam combination therapy for 7 days or more. CONCLUSIONS: Despite the preponderance of Ceftazidime-Avibactam resistant CRE expressing NDM and OXA-48-like carbapenemase in our hospital, 77.2 % of them displayed in-vitro synergy of Ceftazidime-Avibactam with Aztreonam. It emphasizes the potential therapeutic utility of this combination in CRE strains showing coproduction of MBL and serine carbapenemases. Greater therapeutic potential of Ceftazidime-Avibactam and Aztreonam combination was observed with extended duration of therapy. However, further clinical evidence is needed to establish the efficacy of this combination and consider other factors that influence treatment outcomes.


Subject(s)
Azabicyclo Compounds , Aztreonam , Ceftazidime , Adult , Humans , Aztreonam/pharmacology , Aztreonam/therapeutic use , Ceftazidime/pharmacology , Ceftazidime/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Combinations , beta-Lactamases , Carbapenems , Microbial Sensitivity Tests
2.
Eur J Hybrid Imaging ; 7(1): 26, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38036687

ABSTRACT

A 60-year-old male patient diagnosed with mucinous adenocarcinoma of lower third of rectum underwent abdominoperineal resection and permanent colostomy followed by adjuvant chemotherapy. Response evaluation with F-18 FDG PET-CT showed a complete metabolic response. After 6 months, CEA levels started increasing and clinically a recurrence was suspected. A restaging FDG PET-CT showed no obvious malignant disease. Patient presented again within a month with complaints of urinary retention and haematuria. CEA levels were further elevated, and Ga-68 FAPI-04 (FAPI) PET-CT was performed. FAPI PET-CT revealed prostatic and seminal vesicle disease involvement. Additionally, an MRI of pelvis was done and fused with FAPI PET for confirmation of prostatic involvement.

3.
J Fluoresc ; 32(4): 1471-1480, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35482132

ABSTRACT

This paper presents the synthesis of novel organic compound (E)-N-(3-(3-(4(dimethylamino)phenyl)acryloyl)phenyl)quinolone-2-carboxamide, also known as Quinolinecarboxamide Chalcone (QCC) using aldol condensation and carboxamide formation method. The organic sample QCC was examined by FT-IR, 1H NMR, 13C NMR and mass spectroscopic techniques, respectively. Linear and third-order nonlinear optical (TNLO) properties of QCC dissolved in polar solvents such as DMSO, DMF and Ethanol have also been studied. The order of nonlinear refractive index and nonlinear absorption coefficient of QCC was measured to be 10-11 m2/W and 10-5 m/W. The nonlinear refractive index (n2) of QCC was attributed to negative nonlinearity due to self-defocusing effect, and nonlinear absorption coefficient (ß) indicates the behaviors of saturable absorption (SA) and reverse saturable absorption (RSA). The real and imaginary features of the TNLO susceptibility (χ(3)) of QCC in polar solvents were calculated to be the order of 10─7 esu. The spectral characteristics of solvent on TNLO susceptibility of QCC were discussed. The results divulged that the synthesized organic compound is a novel nonlinear optical (NLO) material for applications in photonics and optoelectronics.

4.
Biotechnol Lett ; 42(7): 1287-1304, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32372268

ABSTRACT

BACKGROUND: Mesenchymal Stem Cells (MSCs), regardless of the tissue sources, are considered as excellent candidates for cellular therapy as they are immune-privileged cells containing a multitude of therapeutic functions that aid in tissue regeneration and repair. For the effective application of these cells in cell therapy, it is important to understand and characterize their biological functions. OBJECTIVES: The present study attempts to characterize the variations in multipotent function such as cell surface antigen levels, proliferation, differentiation and stemness (pluripotency) potential of MSCs isolated from foetal [wharton's jelly (WJ), foetal and maternal side of placenta (PF and PM)] and adult tissue sources [bone marrow (BM) and adipose tissue (AT)] using gene expression by real time PCR (qRT-PCR). RESULTS: Amongst the different tissue sources, PM, PF and AT-MSCs exhibited significant increase (p < 0.001, p < 0.001 and p < 0.01 respectively) in CD 73 expression and therefore could have a role in immunomodulation. WJ-MSCs exhibited superior proliferation potential based on growth curve, PCNA and Wnt gene expression. BM-MSCs were superior in exhibiting trilineage differentiation. Enhanced stemness potential (Oct 4 and Nanog) was observed for both BM and WJ-MSCs. In addition, BM and WJ-MSCs expressed high levels of CD 90 making them suitable in bone repair and regeneration. CONCLUSION: Thus to conclude, out of the five different sources tested, BM an adult source and WJ-MSCs a foetal source were superior in exhibiting most of the biological functions indicating that these sources may be suitable candidates for cell repair and regeneration studies.


Subject(s)
Mesenchymal Stem Cells , Transcriptome , Cell Differentiation/genetics , Cell Differentiation/physiology , Cell Proliferation/genetics , Cell Proliferation/physiology , Cells, Cultured , Gene Expression Profiling , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/physiology , Organ Specificity , Transcriptome/genetics , Transcriptome/physiology
5.
J Clin Lipidol ; 13(3): 492-501, 2019.
Article in English | MEDLINE | ID: mdl-30910668

ABSTRACT

BACKGROUND: Evidence on the causal link between plasma triglyceride (TG) levels and risk for cardiovascular disease (CVD) has recently emerged. Individuals with the metabolic syndrome have an increased risk for acquiring elevated TG levels later in life. Moreover, common DNA sequence variations in genes affecting TG levels identify individuals at risk for elevated plasma TG levels. OBJECTIVE: We evaluated whether a 3-single nucleotide polymorphism (SNP) TG gene risk score (GRS) and a metabolic risk score (MetRS) both improved CVD risk prediction. METHODS: A 3-SNP GRS and MetRS were generated in the EPIC-Norfolk cohort (n = 20,074) based on 3 SNPs in LPL and APOA5 or the number of Metabolic Syndrome criteria present (maximum 5), respectively. The associations between the 3-SNP GRS, MetRS, TG levels, and CVD risk were evaluated. RESULTS: The 3-SNP GRS and MetRS were both linearly associated with plasma TG levels, that is, +0.25 mmol/L [95% CI 0.22-0.27] per allele change (P < .001) and +0.72 mmol/L [95% CI 0.70-0.73] per increase of number of metabolic syndrome risk score points (P < .001), respectively. We observed a positive association between the 3-SNP GRS and the risk of CVD with an adjusted hazard ratio (HR) of 1.35 [95% CI 1.04-1.74] for the highest versus the lowest GRS, which was independent of the MetRS. For the MetRS, the adjusted HR was 2.03 [95% CI 1.73-2.40] for the highest versus the lowest MetRS. CONCLUSION: Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD.


Subject(s)
Cardiovascular Diseases/genetics , Cardiovascular Diseases/metabolism , Genetic Predisposition to Disease/genetics , Hypertriglyceridemia/genetics , Hypertriglyceridemia/metabolism , Polymorphism, Single Nucleotide , Triglycerides/genetics , Adult , Aged , Cardiovascular Diseases/blood , Cohort Studies , Female , Humans , Hypertriglyceridemia/blood , Male , Middle Aged , Risk Assessment , Triglycerides/blood
6.
PLoS One ; 13(11): e0205858, 2018.
Article in English | MEDLINE | ID: mdl-30408040

ABSTRACT

GPIHBP1 is a protein localized at the endothelial cell surface that facilitates triglyceride (TG) lipolysis by binding lipoprotein lipase (LPL). Whether Glycosyl Phosphatidyl Inositol high density lipoprotein binding protein 1 (GPIHBP1) function is impaired and may underlie the hyperTG phenotype observed in type 2 diabetes is not yet established. To elucidate the mechanism underlying impaired TG homeostasis in insulin resistance state we studied the effect of insulin on GPIHBP1 protein expression in human microvascular endothelial cells (HMVEC) under flow conditions. Next, we assessed visceral adipose tissue GPIHBP1 protein expression in type 2 diabetes Lepr db/db mouse model as well as in subjects with ranging levels of insulin resistance. We report that insulin reduces the expression of GPIHBP1 protein in HMVECs. Furthermore, GPIHBP1 protein expression in visceral adipose tissue in Lepr db/db mice is significantly reduced as is the active monomeric form of GPIHBP1 as compared to Leprdb/m mice. A similar decrease in GPIHBP1 protein was observed in subjects with increased body weight. GPIHBP1 protein expression was negatively associated with insulin and HOMA-IR. In conclusion, our data suggest that decreased GPIHBP1 availability in insulin resistant state may hamper peripheral lipolysis capacity.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Hypertriglyceridemia/genetics , Intra-Abdominal Fat/metabolism , Receptors, Lipoprotein/genetics , Animals , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Disease Models, Animal , Endothelial Cells/metabolism , Gene Expression Regulation , Humans , Hypertriglyceridemia/metabolism , Hypertriglyceridemia/pathology , Insulin/genetics , Insulin/metabolism , Insulin Resistance/genetics , Lipolysis/genetics , Lipoprotein Lipase/genetics , Mice , Mice, Inbred NOD , Microvessels/metabolism , Triglycerides/genetics , Triglycerides/metabolism
7.
J Assoc Physicians India ; 65(3): 92-94, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28462554

ABSTRACT

Neuroacanthocytosis is a genetic neurodegenerative disorder with syndromes of variable inheritance. These hyperkinetic movement disorders are reported to be very rare. It is associated with choreiform movements, orofacial and lingual dyskinesias and acanthocytes on peripheral smear and normolipoproteinemia. Here we present a similar case.


Subject(s)
Acanthocytes/pathology , Neuroacanthocytosis/diagnosis , Neuroacanthocytosis/pathology , Adult , Humans , Male , Neuroacanthocytosis/drug therapy , Neuroacanthocytosis/genetics
9.
Cytotechnology ; 67(5): 793-807, 2015 Oct.
Article in English | MEDLINE | ID: mdl-24798808

ABSTRACT

The multipotent and immunosuppressive capacities of mesenchymal stem cells (MSCs) attract several scientists worldwide towards translational research focusing on treatment of diseases including liver failure. Though MSC's have been isolated from different sources, researchers do not concur on the best source for expansion and clinical translation. In this study, we have compared the isolation, proliferation and expansion of MSCs from umbilical cord blood (UCB), Wharton's Jelly (WJ), bone marrow (BM) and adipose tissue (AT). MSCs were isolated by density gradient separation from UCB, BM and AT and by both enzymatic and explant method for WJ. The MSCs are characterized by their ability to adhere to plastic, expression of positive (CD105, CD73, CD90, CD29, CD44) and negative (CD45, CD14, CD34) markers by flow cytometry and also by their in vitro adipogenic, osteogenic and chondrogenic differentiation. This comprehensive study clearly shows that WJ is better than UCB both in terms of rapidity, yield and ease of procedure. AT and BM are autologous sources for MSC's but the specimen collection involves cumbersome and painful procedures and an invasive approach. However being autologous, they are safe and probable candidates for therapeutic future applications.

10.
Obesity (Silver Spring) ; 22(5): 1309-16, 2014 May.
Article in English | MEDLINE | ID: mdl-24339435

ABSTRACT

OBJECTIVE: Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated. METHODS: Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1,316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. RESULTS: Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; P = 0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (P < 0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P < 0.05) and retinyl esters levels (P < 0.001). CONCLUSIONS: These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM.


Subject(s)
Diabetes Mellitus, Type 2/blood , Obesity/blood , Postprandial Period , Sulfotransferases/genetics , Triglycerides/blood , Aged , Alleles , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Dyslipidemias/blood , Fasting , Female , Humans , Liver/metabolism , Male , Middle Aged , Obesity/complications , Obesity/genetics , Polymorphism, Single Nucleotide , Postmenopause/physiology , Prospective Studies , Sulfatases
11.
Trop Gastroenterol ; 33(1): 51-4, 2012.
Article in English | MEDLINE | ID: mdl-22803296

ABSTRACT

OBJECTIVE AND BACKGROUND DATA: Reduction in cellular elements of blood, secondary to hypersplenism is an established component of non-cirrhotic portal hypertension. Prior transfusion of blood or blood components is frequently required for safe surgical intervention. Due to thrombocytopenia, epidural catheter insertion for effective and durable analgesia is not possible. The aim of the present study was to objectively demonstrate the gain in blood components following early ligation of splenic artery for splenectomy in shunt surgery. METHODS: From Jan 2008 to July 2010, 30 patients underwent elective proximal spleno renal shunt for portal hypertension, for various indications and were analyzed prospectively. We followed the standard protocol of ligating the splenic artery in situ, first in the lesser sac. Proximal spleno shunt was done. After the surgical procedure and before extubation, an epidural catheter was placed for effective and durable analgesia. 5ml of venous blood was drawn in the following order of sequence: prior to induction of anesthesia, immediately after the ligation of splenic artery, 30 minutes after ligation of splenic artery and 30 minutes after splenectomy. Samples were sent for complete hemogram and values were analyzed in respective order. Patients requiring transfusion of blood or blood components during surgery were excluded from the study. RESULTS: 30 patients (M - 9, F- 21) with mean age of 29.4 years (11-60 years) were analyzed (NCPF- 20, EHPVO- 9, cirrhosis- 1). We objectively demonstrated a significant gain in RBCs (p = 0.016) and platelets (p = 0.000) using this standard protocol. As there were no intrinsic abnormalities in RBCs, red blood cell indices (MCV, MCH, MCHC) showed no changes as expected (p-0.9). CONCLUSION: By following this standard protocol, in addition to reduction in blood loss there was a significant gain in RBCs and platelets. This gain allows the surgeon to perform the surgical procedure safely and the anesthetist to secure an epidural catheter immediately after surgery for effective and durable analgesia without prior transfusion.


Subject(s)
Hypertension, Portal/blood , Hypertension, Portal/surgery , Splenectomy , Splenic Artery/surgery , Splenorenal Shunt, Surgical , Adolescent , Adult , Blood Cell Count , Child , Cohort Studies , Female , Humans , Ligation , Male , Middle Aged , Young Adult
12.
J Intern Med ; 272(2): 185-96, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22239554

ABSTRACT

OBJECTIVES: The severe forms of hypertriglyceridaemia (HTG) are caused by mutations in genes that lead to the loss of function of lipoprotein lipase (LPL). In most patients with severe HTG (TG > 10 mmol L(-1) ), it is a challenge to define the underlying cause. We investigated the molecular basis of severe HTG in patients referred to the Lipid Clinic at the Academic Medical Center Amsterdam. METHODS: The coding regions of LPL, APOC2, APOA5 and two novel genes, lipase maturation factor 1 (LMF1) and GPI-anchored high-density lipoprotein (HDL)-binding protein 1 (GPIHBP1), were sequenced in 86 patients with type 1 and type 5 HTG and 327 controls. RESULTS: In 46 patients (54%), rare DNA sequence variants were identified, comprising variants in LPL (n = 19), APOC2 (n = 1), APOA5 (n = 2), GPIHBP1 (n = 3) and LMF1 (n = 8). In 22 patients (26%), only common variants in LPL (p.Asp36Asn, p.Asn318Ser and p.Ser474Ter) and APOA5 (p.Ser19Trp) could be identified, whereas no mutations were found in 18 patients (21%). In vitro validation revealed that the mutations in LMF1 were not associated with compromised LPL function. Consistent with this, five of the eight LMF1 variants were also found in controls and therefore cannot account for the observed phenotype. CONCLUSIONS: The prevalence of mutations in LPL was 34% and mostly restricted to patients with type 1 HTG. Mutations in GPIHBP1 (n = 3), APOC2 (n = 1) and APOA5 (n = 2) were rare but the associated clinical phenotype was severe. Routine sequencing of candidate genes in severe HTG has improved our understanding of the molecular basis of this phenotype associated with acute pancreatitis and may help to guide future individualized therapeutic strategies.


Subject(s)
Hypertriglyceridemia , Adult , Apolipoprotein A-V , Apolipoprotein C-II/genetics , Apolipoproteins A/genetics , Carrier Proteins/genetics , Female , Genetic Testing , Humans , Hypertriglyceridemia/epidemiology , Hypertriglyceridemia/genetics , Hypertriglyceridemia/physiopathology , Lipoprotein Lipase/genetics , Male , Membrane Proteins/genetics , Molecular Epidemiology , Mutation, Missense , Netherlands/epidemiology , Prevalence , Receptors, Lipoprotein , Severity of Illness Index
13.
Biochim Biophys Acta ; 1821(5): 826-32, 2012 May.
Article in English | MEDLINE | ID: mdl-22179026

ABSTRACT

The importance of triglycerides as risk factor for CVD is currently under debate. The international guidelines do not include TG into their risk calculator despite the recent observations that plasma TG is an independent risk factor for CVD. The understanding of the pathophysiology of triglycerides opens up avenues for development of new drug targets. Hypertriglyceridemia occurs through 1. Abnormalities in hepatic VLDL production, and intestinal chylomicron synthesis 2. Dysfunctional LPL-mediated lipolysis or 3. Impaired remnant clearance. The current review will discuss new aspects in lipolysis by discussing the role of GPIHBP1 and the involvement of apolipoproteins and in the process of hepatic remnant clearance with a focus upon the role of heparin sulfate proteoglycans. Finally we will shortly discuss future perspectives for novel therapies aiming at improving triglyceride homeostasis. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.


Subject(s)
Cardiovascular Diseases , Hypertriglyceridemia , Liver , Triglycerides/blood , Apolipoproteins/metabolism , Cardiovascular Diseases/complications , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Carrier Proteins/metabolism , Chylomicrons/metabolism , Humans , Hypertriglyceridemia/complications , Hypertriglyceridemia/metabolism , Hypertriglyceridemia/physiopathology , Lipolysis , Lipoprotein Lipase/metabolism , Lipoproteins, VLDL/blood , Liver/metabolism , Liver/physiopathology , Receptors, Lipoprotein , Risk Factors
15.
HPB (Oxford) ; 11(8): 638-44, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20495631

ABSTRACT

BACKGROUND: There have been an increasing number of reports world-wide relating improved outcomes after pancreatic resections to high volumes thereby supporting the idea of centralization of pancreatic resectional surgery. To date there has been no collective attempt from India at addressing this issue. This cohort study analysed peri-operative outcomes after pancreatoduodenectomy (PD) at seven major Indian centres. MATERIALS AND METHODS: Between January 2005 and December 2007, retrospective data on PDs, including intra-operative and post-operative factors, were obtained from seven major centres for pancreatic surgery in India. RESULTS: Between January 2005 and December 2007, a total of 718 PDs were performed in India at the seven centres. The median number of PDs performed per year was 34 (range 9-54). The median number of PDs per surgeon per year was 16 (range 7-38). Ninety-four per cent of surgeries were performed for suspected malignancy in the pancreatic head and periampullary region. The median mortality rate per centre was four (range 2-5%). Wound infections were the commonest complication with a median incidence per centre of 18% (range 9.3-32.2%), and the median post-operative duration of hospital stay was 16 days (range 4-100 days). CONCLUSIONS: This is the first multi-centric report of peri-operative outcomes of PD from India. The results from these specialist centers are very acceptable, and appear to support the thrust towards centralization.

16.
HPB (Oxford) ; 10(5): 363-70, 2008.
Article in English | MEDLINE | ID: mdl-18982153

ABSTRACT

UNLABELLED: OBJECTIVE & BACKGROUND DATA: Mortality following pancreatoduodenectomy (PD) has fallen below 5%, yet morbidity remains between 30 and 50%. Major haemorrhage following PD makes a significant contribution to this ongoing morbidity and mortality. The aim of the present study was to validate the new International Study Group of Pancreatic Surgery (ISGPS) Clinical grading system in predicting the outcome of post pancreaticoduodenectomy haemorrhage (PPH). MATERIAL AND METHODS: Between January 1998 and December 2007 a total of 458 patients who underwent Whipple's pancreaticoduodenectomy in our department were analysed with regard to haemorrhagic complications. The onset, location and severity of haemorrhage were classified according to the new criteria developed by an ISGPS. Risk factors for haemorrhage, management and outcome were analysed. RESULTS: Severe PPH occurred in 14 patients (3.1%). Early haemorrhage (<24 hours) was recorded in five (36%) patients, and late haemorrhage (>24 hours) in nine (64%) patients. As per Clinical grading of ISGPS 7 (50%) belongs to Grade C and 7 (50%) belongs to Grade B. Haemostasis was attempted by surgery in 10 (71%) patients; angioembolisation was successful in two (14%) and endotherapy in one (7%) patient. The overall mortality is 29%(n=4). Age >60 years (p=0.02), sentinel bleeding (p=0.04), pancreatic leak (p=0.04) and ISGPS Clinical grade C (p=0.02) were associated with increased mortality. CONCLUSION: Early haemorrhage was mostly managed surgically with better outcome when endoscopy is not feasible. Late haemorrhage is associated with high mortality due to pancreatic leak and sepsis. ISGPS Clinical grading of PPH is useful in predicting the outcome.

17.
Int J Infect Dis ; 12(6): e71-6, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18658001

ABSTRACT

OBJECTIVES: The prevalence of hepatitis B virus (HBV) is reportedly the main cause of hepatocellular carcinoma (HCC) in India, where hepatitis C virus (HCV)-associated HCC is believed to be relatively less prevalent. We verified the usefulness of alpha-fetoprotein (AFP) as a tumor marker and analyzed the influence of viral etiology on AFP levels in HCC. METHODS: Of a total of 1012 cases with liver disease, 202 were investigated for the presence of AFP (142 HCC cases, 30 cirrhosis cases, and 30 chronic liver disease (CLD) cases). In addition, serum samples from 30 healthy patients, 30 hepatitis B surface antigen (HBsAg) carriers, and 30 acute viral hepatitis cases were included as controls. AFP was quantitatively determined using a commercial ELISA (Quorum Diagnostics, Canada). Out of the 142 HCC cases screened for AFP, aflatoxin B1 (AFB1) detection was carried out in 38 HCC cases using an in-house immunoperoxidase test. RESULTS: In HBV and HCV co-infected HCC cases, the AFP positivity was 85.7%. In HBV alone-associated HCC, the positivity was 62.9%, and 54.5% of AFB1 positive HCC cases showed AFP positivity. In HBV and HCV negative HCC cases, the positivity was 20.5%, and in HCV-associated HCC it was 17.6%. The HBV/HCV co-infected group and HBV alone positive HCC cases had significantly elevated levels of AFP. When AFP positivity was analyzed based on the marker profile of HBV, 89.7% of AFP positive cases were HBV-DNA positive. CONCLUSIONS: The overall positivity pattern of AFP in HCC does indicate that higher levels of AFP are observed with hepatitis virus positivity, especially with HBV. Further studies must be carried out to correlate the serum levels of AFP with the size, number, and degree of differentiation of HCC nodules.


Subject(s)
Aflatoxins/analysis , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular , Liver Neoplasms , alpha-Fetoproteins/metabolism , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/virology , Carrier State/metabolism , Female , Hepacivirus/isolation & purification , Hepatitis B/complications , Hepatitis B/metabolism , Hepatitis B/virology , Hepatitis B Surface Antigens/analysis , Hepatitis C/complications , Hepatitis C/metabolism , Hepatitis C/virology , Humans , India , Liver Cirrhosis/complications , Liver Cirrhosis/metabolism , Liver Cirrhosis/virology , Liver Neoplasms/etiology , Liver Neoplasms/metabolism , Liver Neoplasms/virology , Male , Middle Aged
18.
Indian J Med Res ; 126(3): 204-10, 2007 Sep.
Article in English | MEDLINE | ID: mdl-18037714

ABSTRACT

BACKGROUND & OBJECTIVE: Liver cirrhosis is associated with gastrointestinal haemorrhage and oesophageal variceal bleeding. Altered platelet functions has been reported to be a cause of bleeding complication. We carried out this study to find out the level of oxidative stress in the red blood cells of patients with liver cirrhosis. METHODS: Fifty patients admitted with the complication of liver cirrhosis (with bleeding complications, n=30 and without bleeding complications, n=20) were included in the study. Age and sex matched normal healthy volunteers (n=45) served as controls. The levels of oxyhaemoglobin and methaemoglobin were assayed in the red blood cells. Oxidative stress markers such as lipid peroxides, lipid hydroperoxides and nitric oxide were determined along with enzymatic antioxidants. Membrane bound adenosine triphosphatases, cytosolic glucose-6-phosphate dehydrogenase and NADHmethaemoglobin reductase were also measured. The levels of cholesterol and total phospholipids were assessed in red blood cell membrane. The osmotic fragility of red blood cells was monitored using different concentrations of sodium chloride. RESULTS: The level of methaemoglobin was significantly higher (P < 0.001) in the red blood cells of liver cirrhotic patients with bleeding complication compared to that of non bleeding patients. The activity level of NADH-methaemoglobin reductase was significantly lower (P<0.001) compared to that of normal subjects. Levels of oxidative stress markers including nitric oxide were found to be higher in patients. The levels of enzymatic antioxidants were low except of glutathione peroxidase. The activity levels of adenosine triphosphatases were also found to be significantly lower (P<0.001) in patients compared to normal subjects. A significant alteration (P<0.05) was found in membrane cholesterol/phospholipid ratio of cirrhotic bleeders. Osmotic fragility of red blood cells was also altered in patients. INTERPRETATION & CONCLUSION: In cirrhotic condition red blood cells are subjected to severe oxidative stress with significant alterations in the membrane properties.


Subject(s)
Erythrocytes/metabolism , Liver Cirrhosis/metabolism , Oxidative Stress/physiology , Adenosine Triphosphate/analysis , Adult , Analysis of Variance , Erythrocytes/chemistry , Female , Glucosephosphate Dehydrogenase/analysis , Hemoglobins/analysis , Humans , Lipid Peroxides/analysis , Male
19.
J Med Microbiol ; 56(Pt 11): 1455-1459, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17965344

ABSTRACT

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death in the world. The incidence of HCC in India is reportedly low and varies from 0.2 to 1.9 %. Aflatoxins, secondary metabolites produced by Aspergillus flavus and Aspergillus parasiticus, are potent human carcinogens implicated in HCC. The prevalence of aflatoxin B1 (AFB1) as co-carcinogen was analysed using an in-house immunoperoxidase test in 31 liver biopsies and 7 liver-resection specimens from histopathologically proven HCC, and in 15 liver biopsies from cirrhosis patients (control group). Serum was tested for hepatitis B and C serological markers using commercial assays, and for AFB1 using an in-house ELISA with a sensitivity of approximately 1 ng ml(-1) for AFB1. In spite of positive AFB1 immunostaining in HCC cases, all serum specimens, from both HCC and the control groups, were AFB1-negative. There were 18 (58.1 %) HCC cases that revealed AFB1 in liver biopsies; 68.8 % (n=11) of non-B non-C hepatitis cases with HCC and 46.1 % (n=6) of the hepatitis B surface-antigen-positive subjects were positive for AFB1. Out of the two hepatitis B/hepatitis C virus co-infected cases, one was positive for AFB1. Of seven tumour-resection samples, six were positive for AFB1. Only one case revealed AFB1 in the non-tumour area of the resected material. Thus AFB1 staining was significantly associated with tumour tissue (P=0.03). Aflatoxins proved to have a significant association with HCC in this peninsular part of the subcontinent. The impact seems to be a cumulative process, as revealed by the AFB1 deposits in HCC liver tissue, even though the serum levels were undetectable.


Subject(s)
Aflatoxin B1/analysis , Carcinoma, Hepatocellular/pathology , Enzyme-Linked Immunosorbent Assay/methods , Liver/chemistry , Adult , Aged , Aged, 80 and over , Biopsy , Female , Hepatitis B Surface Antigens/blood , Hepatitis C Antibodies/blood , Humans , India , Male , Middle Aged , Serum/chemistry
20.
Dis Esophagus ; 20(4): 328-32, 2007.
Article in English | MEDLINE | ID: mdl-17617882

ABSTRACT

Pharyngo-esophageal corrosive stricture is a complex clinical scenario. If an esophageal opening cannot be found orally through endoscopy, a retrograde approach with a mini-laparotomy and gastrostomy should be attempted. This study primarily aimed at defining the role of preoperative retrograde dilatation of pharyngo-esophageal corrosive strictures. A retrospective analysis of 51 cases of pharyngo-esophageal corrosive strictures identified between 1997-2005 was performed. The demographic details were analyzed. The details of the injury to the pharynx either in isolation or in combination were noted and the management details were recorded. In 21 patients preoperative retrograde dilatation was considered and the technique was successful in 14 (Group I). In seven the technique failed (Group II) and these patients underwent transhiatal resection and gastric pull-through and/or retrosternal pharyngocoloplasty. In Group I patients the postoperative stay was significantly less than in Group II (12 +/- 2.03 days vs. 18 +/- 4.32 days; p = 0.001) Recurrent aspiration, respiratory tract infections, choking sensation and the need for tracheostomy were less frequent in Group I. The overall functional assessment was good in Group I. For treatment of pharyngo-esophageal obstruction, if antegrade dilatation is not possible due to technical reasons, retrograde dilatation is a viable option before opting for organ replacement/bypass procedures. There is no best replacement of the native organ to maintain quality of life.


Subject(s)
Burns, Chemical/complications , Esophageal Stenosis/chemically induced , Esophageal Stenosis/therapy , Pharyngeal Diseases/chemically induced , Pharyngeal Diseases/therapy , Adult , Dilatation/methods , Female , Humans , Male , Retrospective Studies
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