N-acetyl-beta-D-glucosaminidase in acute myocardial infarction

The objective of the study was to investigate whether the lysosomal enzyme, N-Acetyl-beta-D-glucosaminidase (NAG) activity is increased in plasma of patients with acute myocardial infarction (AMI) and to determine if there is any association between plasma levels of NAG and severity of myocardial infarction (MI). NAG activity in plasma was monitored in 69 patients with AMI and 135 normal healthy subjects using a spectrofluorimetric method. A modified Aldrich ST elevation score was used to gauge the severity of MI in terms of size of the infarct. Plasma NAG levels in AMI patients and normal healthy subjects were found to be 10.92+/-7.5 U/l and 6.8+/-2.2 U/l, respectively. These two mean value when compared by Student\u27s t-test were significantly different P = 0.0001. No statistically significant differences in NAG activity were observed in patients in terms of gender, age, location of infarct, time from onset of chest pain to blood sampling in the hospital and size of the infarct

Comparative study of Pap smear abnormalities in HIV infected and HIV non-infected women

Background: HIV positive women are more likely than HIV negative women to have cervical dysplasia. Incidence of HPV-related dysplasia increases as immune function declines. To analyse the prevalence of cervical dysplasia on papsmear among women affected with HIV and to compare with that of HIV negative women.Methods: The study period was of 6 months duration from December 2010 to May 2011. Cervical cytology specimen from HIV positive and HIV negative women who attended the OPD of Institute of Maternal and Child Health, Government Medical College, Kozhikode. Were collected after excluding known case of carcinoma cervix, post hysterectomy patients, patients with bleeding per vagina and also those with active genital tract infections.Results: A prospective study of 200 females (100 HIV positive and 100 HIV negative) was done in our hospital. Age range was between 36 and 50 years. PAP smear abnormality was obtained in 35% of the study group. Out of which 21% was seen in HIV positive patients and 14% in HIV negative patients. Prevalence of LSIL (low grade squamous intraepithelial lesion) was significantly higher among HIV positive patients. Abnormality was not associated with CD4 count, HIV status of husband or addictions of husband, not associated with number of partners of husband both in HIV positive and negative patients.Conclusions: PAP smear abnormality (overall), prevalence of LSIL was significantly higher among HIV positive patients. It was not associated with SES, age of first intercourse, number of partners of wife and other immunosuppressive status

Insight into the molecular pathophysiology of myelodysplastic syndromes: targets for novel therapy

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by abnormal cellular differentiation and maturation with variable progression to acute leukemia. Over the last decade, scientific discoveries have unraveled specific pathways involved in the complex pathophysiology of MDS. Prominent examples include aberrations in cytokines and their signaling pathways (such as tumor necrosis factor-alpha, interferon-gamma, SMAD proteins), mutations in genes encoding the RNA splicing machinery (SF3B1, SRSF2, ZRSR2, and U2AF1 genes), mutations in genes disrupting the epigenetic machinery (TET2, DNMT3A, DNMT3B, EZH2, ASXL1). In addition, abnormalities in regulatory T-cell dynamics and atypical interactions between the bone marrow microenvironment, stroma and progenitor cells, and abnormal maintenance of telomeres are also notable contributors to the complex pathogenesis of MDS. These pathways represent potential targets for novel therapies. Specific therapies include drugs targeting aberrant DNA methylation and chromatin remodeling, modulating/activating the immune system to enhance tumor-specific cellular immune responses and reduce anomalous cytokine signaling, and blocking abnormal interaction between hematopoietic progenitors and stromal cells

Folic acid and vitamin B6 deficiencies related hyperhomocysteinemia in apparently healthy Pakistani adults; is mass micronutrient supplementation indicated in this population

OBJECTIVE: To determine the plasma/serum levels of homocysteine, and vitamins folate, B6 and B12, in Pakistani healthy adults.STUDY DESIGN: Cross-sectional study.PLACE AND DURATION OF STUDY: The Aga Khan University, from October 2006 to April 2008.METHODOLOGY: Fasting levels of plasma/serum folic acid, pyridoxal phosphate (PLP), vitamin B12 and homocysteine were determined in 290 apparently healthy hospital personnel from institutions in two cities of Pakistan. Spearman correlation test and linear regression analysis was conducted.RESULTS: There were 219 males and 71 females with mean age of 46+/-10.5 years and mean body mass index of 23.5 +/-3.8. Mean plasma homocysteine levels in Pakistani normal adults were found to be 17.95+/-8.4 micromol/l. Mean concentrations of plasma/serum folate, vitamin B12 and PLP were found to be 5+/-3.9 ng/ml, 522+/-296 pg/ml and 21.6+/-14 nmol/l, respectively. Serum/plasma levels of folate, vitamin B12 and PLP were negatively correlated with plasma homocysteine (rho coefficient=-0.367,

N-acetyl-B-D-glucosaminidase and inflammatory response after cardiopulmonary bypass

OBJECTIVE: To determine the changes in activity of plasma N-acetyl-beta-D-glucosaminidase, a marker for inflammation as well as renal, pulmonary and cardiac damage and proinflammatory cytokines in patients undergoing coronary artery bypass grafting and find out the relationship between their plasma levels with clinical outcome of patients. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: The Aga Khan University, Karachi, from January to June 2003. PATIENTS AND METHODS: N-acetyl-beta-D-glucosaminidase (NAG) activity and concentrations of tumor necrosis factor-alpha of (TNFalpha), interleukin 6 (IL-6), interleukin 8 (IL8) and granulocyte-macrophage colony stimulating factor (GM-CSF) were monitored in plasma samples of 12 angina patients undergoing coronary artery bypass grafting (CABG), before, immediately after and 5 days post-surgical procedure. Serum glucose concentrations were also monitored in those patients. Patient\u27s clinical condition was monitored during this time period. RESULTS: No significant increase was observed in plasma NAG activity (a marker of inflammation) or in plasma levels of TNFalpha, IL-6, IL-8 and GM-CSF immediately after surgery, indicating that cardiopulmonary bypass itself does not produce any significant amount of inflammation immediately after CABG. However, 5 days post surgery, there was a significant increase in plasma NAG activity (p=0.001), TNFalpha (p=0.047) and GM-CSF (p=0.045). There was no relationship between plasma NAG activity and clinical outcome because various parameters of renal, cardiac and pulmonary functions, though slightly affected, remained within the normal limits. CONCLUSION: Increased levels of NAG and TNFalpha did not affect clinical outcome. However, data suggest that NAG can be a potential marker for inflammation and end organ damage following CABG. An increase in GM-CSF on day 5 following CABG indicates enhanced body\u27s defense mechanism against infection

Lack of association of methylenetetrahydrofolate reductase 677C\u3eT mutation with coronary artery disease in a Pakistani population

Pakistanis belong to the South Asian population which has the highest known rate of coronary artery disease. Folic acid deficiency also appears to be highly prevalent in this population. Methylenetetrahydrofolate reductase (MTHFR) 677C\u3eT polymorphism decreases the activity of this enzyme and can be associated with mild to moderate hyperhomocysteinemia in homozygotes, particularly when there is folic acid deficiency, as well as with coronary artery disease. To assess the value of genotyping the MTHFR 677C\u3eT dimorphism, we carried out a case-control study of dimorphism 677C\u3eT for putative association with myocardial infarction (MI) among Pakistani nationals. We investigated a sample population of 622 Pakistanis consisting of 225 controls and 397 patients with clinical diagnosis of acute MI (AMI). MTHFR C677T alleles were determined by assays based on polymerase chain reaction and restriction endonuclease analysis. Frequencies of C alleles were 0.87 among controls and 0.86 among AMI patients. The MTHFR 677C\u3eT dimorphism showed no association with MI (chi(2) = 0.25, 1df, P=0.62), serum levels of folate and vitamin B12 and plasma level of vitamin B6. A significant association, however, was found between homozygous 677T genotype and plasma levels of homocysteine. Multivariate analysis of the data showed that in case of log homocysteine, age and MTHFR genotypes were significantly different (PT polymorphism, though associated with homocysteine levels, confers no significant risk of coronary artery disease in the Pakistani population investigated here. We suggest that the higher incidence of AMI in South Asia occurs through mechanisms other than the MTHFR related pathways

Pregnancy in patients with myelofibrosis: Mayo–Florence series of 24 pregnancies in 16 women

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A globally applicable “triple A” risk model for essential thrombocythemia based on Age, Absolute neutrophil count, and Absolute lymphocyte count

: We examined the individual prognostic contribution of absolute neutrophil (ANC), lymphocyte (ALC), and monocyte (AMC) counts, on overall (OS), leukemia-free (LFS), and myelofibrosis-free (MFFS) survival in essential thrombocythemia (ET). Informative cases (N = 598; median age 59 years; females 62%) were retrospectively accrued from a Mayo Clinic database: JAK2 59%, CALR 27%, triple-negative 11%, and MPL 3%; international prognostic scoring system for ET (IPSET) risk high 21%, intermediate 42%, and low 37%; 7% (37/515) had abnormal karyotype and 10% (21/205) adverse mutations (SF3B1/SRSF2/U2AF1/TP53). At median 8.4 years, 163 (27%) deaths, 71 (12%) fibrotic, and 20 (3%) leukemic transformations were recorded. Multivariable analysis resulted in HR (95% CI) of 16.5 (9.9-27.4) for age > 70 years, 3.7 (2.3-6.0) for age 50-70 years, 2.4 (1.7-3.3) for ANC ≥8 × 109 /L, and 1.9 (1.4-2.6) for ALC <1.7 × 109 /L. The corresponding HR-based scores were 4, 2, 1, and 1, resulting in an new 4-tiered AgeAncAlc (AAA; triple A) risk model: high (5-6 points; median survival 8 years; HR 30.1, 95% CI 17.6-54), intermediate-2 (4 points; median 13.5 years; HR 12.7, 95% CI 7.1-23.0), intermediate-1 (2-3 points; median 20.7 years; HR 3.8, 95% CI 2.3-6.4) and low (0-1 points; median 47 years). The AAA model (Akaike Information Criterion [AIC] 621) performed better than IPSET (AIC 647) and was subsequently validated by an external University of Florence ET cohort (N = 485). None of the AAA variables predicted LFS while ALC <1.7 × 109 /L was associated with inferior MFFS (p = .01). Adverse mutations (p < .01) and karyotype (p < .01) displayed additional prognostic value without disqualifying the prognostic integrity of the AAA model. This study proposes a simple and globally applicable survival model for ET, which can be used as a platform for further molecular refinement. This study also suggests a potential role for immune-related biomarkers, as a prognostic tool in myeloproliferative neoplasms