Tumor Necrosis Factor-Α, Interleukin-6, C-Reactive Protein Levels and Insulin Resistance Associated with Type 2 Diabetes in Abdominal Obesity Women

We aim to investigate the association between elevated tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and high sensitivity-C-reactive protein (hs-CRP) with type 2 diabetes mellitus (T2DM) in abdominal obesity (AO) women subjects. A total of 428 AO subjects (age 48.4 ± 10.2 years), and 107 non-AO women subjects (age 48.8 ± 11.8 years) were enrolled for the all biochemistry testing, inflammatory cytokines, fasting insulin and Homeostasis Model Assessment of insulin resistance (HOMA-IR). Body mass index, waist circumference (WC), blood pressure (BP), plasma glucose (Glu), triglyceride (TG), insulin, HOMA-IR and inflammatory cytokines were significantly higher and lower total antioxidant capacity, HDL-C in AO subjects (p < 0.05). WC was significantly correlated with BP, Glu, TG, LDL-C, insulin, HOMA-IR, TNF-α, IL-6 and negative correlation with HDL-C in AO subjects. Elevation of TNF-α, IL-6, hs-CRP and insulin resistance were significantly associated with T2DM in AO subjects, after adjusting with insulin resistance, increased oxidative stress, elevated TG and reduced HDL-C by using multiple logistic regression analysis. In conclusions, elevation of inflammatory cytokines, oxidative stress and insulin resistance were associated with T2DM in AO women subjects. These inflammatory cytokines are positively associated with T2DM and may have a causal relation with an increased oxidative stress and insulin resistance in these AO women subjects.     

Cardiac troponin-T and CK-MB (mass) levels in cardiac and non cardiac disease

Serum cardiac troponin T (cTnT) and CKMB (mass) were analysed in three groups of patients. The first group (n=32) were patients with acute coronary syndromes including myocardial infarction. The second group (n=35)were patients with hypertension. The third group (n=24) were patients who had succumbed to non cardiac diseases. In all 3 groups, cardiac troponin T was elevated when compared with controls (p<0.001). However, CKMB elevation was not significant in all groups. CKMB levels correlated well with troponin T levels only when CKMB was greater than 50 ng/ml (r=1.00). Small elevations of troponin T identifies minimal cardiac necrosis and patients can benefit from early invasive therapy.     

Evaluation of clinical utility of serum enzymes and troponin—T in the early stages of acute myocardial infarction

Laboratory infarction diagnostics are based on the detection of elevated serum activities of total Creatine Kinase (CK), Creatine Kinase isoensyme MB, (CKMB), Lactate dehydrogenase (LDH), isoenzyme forms of LDH and transaminases. Determination of these cardiac marker enzymes permits a highly sensitive diagnosis of transmural myocardial infarction. In such patients the diagnosis of acute myocardial infarction can be confirmed by the clinical, symptoms, and changes in the ECG in addition to the enzyme assays. The 50 AMI patients selected in the present study were those admitted to the ICCU of Shri Krishna Hospital, Karamsad. The blood samples were taken at the time of admission (ie. within four hours of the start of chest pain). The samples were analyzed for CK, CKMB, SGOT, (Serum glutamate oxaloactate transaminase) αHBDH α-hydroxybutyrate dehydrogenase and troponin T. The serum CKMB activity in AMI showed an increase only 5–6 hours after the commencement of chest pain. The elevation in SGOT and αHBDH was still delayed. At the same time we could observe that the cardiac Troponin T (cTnT) was elevated at the time of admission of the patient itself. This increase of cTnT in AMI patients was 20 times higher than the normal blood donors. The controls included 25 normal blood donors and 25 patients with polytraumatic injuries with no chest contusion. The study shows that cTnT estimation could serve in the early diagnosis of AMI. The increase of cardiac troponin T in AMI patients was 20 times higher than the normal blood donors in AMI patients at the time of admission. Cardiac troponin T in serum appears to be a more sensitive indicator of myocardial cell injury than CKMB activity and its detection in the circulation may be a useful prognostic indicator in patients with unstable angina as well. When the blood of normal blood donors or that of patients with polytraumatic injury was analysed the troponin T values were well within the normal range in both the above categories showing that cardiac troponin T is highly specific for heart tissue. Although CKMB and cardiac troponin T are released soon after the myocardial injury, the release of cardiac troponin T is much earlier than CKMB thereby invalidating the important role of cardiac troponin T in diagnosing AMI. Cardiac troponin T has been shown to be highly sensitive for cardiac injury and not elevated in any other trauma, heavy exercise or skeletal muscle injury. Cardiac troponin T is ordinarily undetectable in healthy individuals, and so its measurement can serve as a powerful tool in the diagnosis of AMI.     

Association of Inflammatory Cytokines,Lipid Peroxidation End Products and Nitric Oxide with the Clinical Severity and Fetal Outcome in Preeclampsia in Indian Women

Preeclampsia is a multisystem disorder associated with maternal hypertension, placental abnormalities and adverse fetal outcomes. The various pathways involved in its etiology include endothelial dysfunction, inflammatory milieu, lipid peroxidation and immunological imbalance. The present study was conducted to evaluate the causative and predictive role of nitric oxide, lipid peroxidation end products (MDA) and inflammatory cytokines (IL-6, TNF-α) in clinical presentation, severity and fetal outcome in preeclampsia. The study population was divided into 3 groups- Non- pregnant females comprising the control population; G1 and G2 groups included normal pregnant and pregnant females with preeclampsia with 50 patients in each group. Nitric Oxide and MDA levels were found to be highest in the preeclamptic patients as compared to other two groups. ROC curve analysis shows the superiority of the inflammatory markers as determinants of severity of preeclampsia which suggests the emerging role of pro inflammatory markers in the various pathological changes in preeclampsia. TNF-α emerged as the best marker in multivariate analysis and thus, has the potential for being used as a marker for PIH. Our study illustrates the multifactorial etiology of preeclampsia involving oxidative stress, proinflammatory milieu and endothelial dysfunction.     

Efficacy of Tumor Necrosis Factor and Interleukin-10 Analysis in the Follow-up of Nonalcoholic Fatty Liver Disease Progression

Tumor necrosis factor (TNF-α) is a cytokine involved in systemic inflammation during acute phase reactions. The current study was designed to investigate the levels of pro-inflammatory cytokine (TNF-α) along with the anti-inflammatory cytokine (IL-10) during progression of non-alcoholic fatty liver disease (NAFLD) from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis in diabetic patients, and correlate the levels of cytokines with the progression of NAFLD. Fifty-two diabetic patients compared to 18 healthy controls were participated in this study. Based on clinical diagnosis, patients were divided into three groups: simple steatosis, NASH and fibrosis. Serum liver function tests, fasting blood glucose, bilirubin, ALT, AST, TNF-α, IL-10 and lipid profile were measured. TNF-α levels were significantly higher in NAFLD patients compared to control subjects with a significant positive correlation with body mass index and fasting blood glucose (FBG) but with negative correlation with IL-10. Serum IL-10 levels were significantly lower in NAFLD patients compared with controls. A positive correlation between IL-10 and HDL-C with concomitant negative correlation between IL-10 and FBG and triacylglycerides was found. Cytokine analyses showed that there was a prominent imbalance between TNF-α and IL-10 in patients with NAFLD, and this imbalance increase by increasing the progression of NAFLD especially in obese diabetic patients. TNF-α and IL-10 could be used in diagnosis and follow-up of NAFLD stages in a way to avoid liver biopsies in greater proportion of patients.     

Relationship between serum interleukin-1beta levels and acute phase response proteins in patients with familial Mediterranean fever

Introduction:

The aim of this study was to investigate whether serum levels of interleukin-1β (IL–1β) has any possible correlation on inflammatory parameters such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fibrinogen concentration in patients with familial Mediterranean fever (FMF) patients during attack-free period.

Materials and methods:

The serum levels of IL-1β, as an indicator of cytokines status, and the acute phase response proteins, CRP, ESR and fibrinogen levels were evaluated in 35 attack-free patients with FMF and 25 healthy volunteers.

Results:

Serum IL-1β levels were significantly higher in patients with FMF than control subjects (P = 0.018). There was no statistically significant difference in the serum levels of ESR, CRP and fibrinogen between two groups (P = 0.181, P = 0.816, P = 0.686, respectively). There was a significant correlation between IL-1β and CRP (r = 0.513, P = 0.002) values of FMF group.

Conclusions:

In conclusion, our results confirm the presence of increased IL-1β levels in FMF patients during attack-free period. Serum IL-1β values seems to correlate with CRP levels. The elevation of IL-1β levels may be important in monitoring subclinical inflammation of attack free period in FMF patients.     

冠心病患者血浆内皮素含量测定

为探讨血浆内皮素对冠心病患者的意义,采用放射免疫分析法对４９例健康人与２０例冠心病患者进行血浆内皮素含量测定。结果表明冠心病患者血浆内皮素含量明显高于健康人,差异非常显著,Ｐ〈０．０１,说明血浆内皮素含量升高对冠心病的发生和发展具有重要作用。     

Estimation of mRNA levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-4 and interferon (IFN)-γ in HIV infected children in Mumbai

Cytokines, viral load and opportunistic infections play an important role in HIV-disease progression. Hundred children vertically infected with HIV were enrolled to determine mRNA levels of TNF-α, IL-10, IL-4 and IFN-γ. These levels were estimated by amplifying cytokine mRNA from peripheral blood mononuclear cells. Severity of HIV was staged by the reduction in CD₄ ⁺ T cells and the onset of opportunistic infections. IL-10 mRNA levels were observed to increase with the severity. Despite the rising IL-10 mRNA levels, TNF-α mRNA levels increased with severity of HIV and decrease in CD₄ ⁺ T cell counts. IL-4 mRNA levels increased with the reduction in CD₄ ⁺ T cell numbers. Depleting mRNA levels of IFN-γ contributed to the worsening of HIV disease. Increase in TNF-α and IL-4 levels appended to the disease severity by upregulation of the viral replication. Increased IL-10 levels and decreased IFN-γ levels predisposed the children to HIV associated opportunistic infections, which in return contributed to cytokine disarray.     

Comparison of Mass Versus Activity of Creatine Kinase MB and Its Utility in the Early Diagnosis of Re-infarction

Currently employed markers for the detection of acute coronary syndrome are Troponin T, CK (Creatine Kinase) and CKMB activity. CKMB activity measured by immunoinhibition method can give falsely elevated results due to the presence of atypical CK and CKBB and at times lead to the mis-diagnosis of acute coronary syndrome. Hence, CKMB mass (CKMB) measured by electrochemiluminence sandwich principle was employed. In this cross-sectional study 183 samples of 61 patients were analyzed within 6 h of diagnosis of acute coronary syndrome and followed up to 72 h. The correlation coefficient between CKMB activity and CKMBM at 4–6 h was 0.744, while at 12–24 h it was 0.909 and at 48–72 h it was 0.337. Thus there was good association between the two methods at 12–24 h but, statistically for method comparison studies and for replacing one method by another, the two methods need to be in agreement with one another. In this study the two methods are not in agreement with one another and thus analytically not replaceable. Another finding was obtained that CKMBM reached cut off levels prior to CKMB enzyme activity and hence, CKMBM is clinically better than CKMB activity to detect reinfarction.     

Lipoprotein (A): Better assessor of coronary heart disease risk in south Indian population

In an attempt to search for risk factors which can explain the increasing prevalence of coronary heart disease (CHD) in Indian population, we conducted a case-control study to assess the association of Lipoprotein (a)(Lp(a)) with CHD. One hundred and fifty one consecutive patients with clinical and angiographic evidence of CHD and forty-nine healthy controls were drawn for the study. Triglycerides, very low density cholesterol (VLDL-C), total cholesterol (total-C)/high density cholesterol (HDL-C) ratio, low density cholesterol (LDL-C)/HDL cholesterol ratio and Lp(a) were found to be higher in patients than controls. In female sex and in those with family history of CHD, higher total and LDL cholesterol levels were observed to be associated with higher Lp(a) levels. Lp(a) levels were also found to be higher in triple vessel disease than other vessel disease patients. Significant difference in Lp(a) levels were observed between normal coronaries vs. single and triple vessel disease(P<0.05) and also between single vs. double and triple vessel disease (P<0.01).Lp(a) levels correlated positively with vessel severity(P<0.005). Lp(a) levels >25 mg/dl were associated with coronary heart disease (Odds ratio 1.98 P<0.05 95% CI 0.007–1.18). Our findings suggest a cut-off level of 25mg/dl for determination of risk of CHD. Studies from different areas involving larger sample size are needed to confirm the findings of the present study.     

Study of genetic, metabolic and inflammatory risk factors in patients of acute ischemic stroke

Stroke is the third leading cause of death and foremost cause of disability. Based on studies in CAD patients, a focus has been shifted on genetic and inflammatory markers as risk factors for stroke besides deranged lipid profile. The present study was aimed to ascertain the role of Lipoprotein (a), C-Reactive protein (CRP) levels and lipids in patients of ischemic stroke. The study was done in 82 subjects including 40 Computerized Tomography (CT) proven patients of ischemic stroke and 42 age and sex matched controls. Complete biochemical parameters including lipid profile were carried out on autoanalyzer using standard kits and reagents. Lipoprotein (a) [Lp(a)] was determined by immunoturbidimetric assay. Atherogenic indices (Total cholesterol/ HDL, LDL/HDL and Lipid Tetrad Index) were calculated using these lipid parameters. The CRP levels were measured semi-quantitatively by latex agglutination test method. Out of 40 stroke patients, 38 had abnormalities in lipid profile (As per ATP III guidelines). A significant difference was seen in serum cholesterol, LDL cholesterol and atherogenic indices between the patients and controls. The difference in CRP levels in cases and control subjects was highly significant (4.78±0.72 mg/dl vs 0.76 ±0.70, p<0.001). 96.5% of patients with raised CRP had abnormal lipid levels also. CRP levels in stroke patients showed significant correlation with total cholesterol and LDL (p<0.001), Lp (a) (p=0.002) and atherogenic indices (p<0.05). Raised CRP levels in stroke patients were significantly associated with large territory infarcts, severe disability and poor functional outcome (p<0.05).Genetic [Lp(a)], metabolic (deranged Lipid profile) and inflammatory factors (CRP) together are instrumental in causing cerebrovascular arteriosclerosis leading to ischaemic stroke and can be used as important markers to identify patients at risk of severe stroke and to institute aggressive preventive strategies.     

Cytokine Gene Polymorphism in Idiopathic Nephrotic Syndrome Children

The pathogenesis of idiopathic nephrotic syndrome is not completely understood. We postulate that cytokine gene polymorphisms may influence susceptibility or clinical course in Idiopathic Nephrotic Syndrome. Polymorphisms of IL-4, IL-6, and TNF-α cytokines were investigated in 150 children with Idiopathic Nephrotic Syndrome and 569 healthy controls by using polymerase chain reaction and restriction fragment length polymorphism. On comparing patient with controls strong association were found for IL-6, TNF-α and IL-4 at allelic level (IL-6-G174C (G vs. C): P = <0.001; OR = 6.33, TNF-α-G308A (G vs. A): P = <0.001; OR = 1.99, IL-4-C590T (C vs. T): P = 0.048; OR = 1.38). Further when SR group was compared with SS group significant association was found at genotypic level in all the studied genetic polymorphisms. Studied cytokine gene polymorphisms may influence susceptibility to idiopathic nephrotic syndrome and might affect steroid response in INS patients.     

血浆纤维蛋白原含量升高与冠心病

用盐析－双缩脲法对９７例健康人和７９例冠心病患者进行了血浆纤维蛋白原含量的测定，结果表明：冠心病患者血浆纤维蛋白原含量显著高于健康人（Ｐ＜０．０１），提示纤维蛋白原含量升高是冠心病、中风、血栓形成的一种重要的危险因素．对血浆纤维蛋白原进行检测，将为冠心病的临床诊断及预防提供依据     

Glycogen phosphorylase isoenzyme BB in the diagnosis of acute myocardial infarction: a meta-analysis

Background

Early diagnosis is crucial for management of patients with suspected acute myocardial infarction (AMI). Among innovative and promising biomarkers, the recent interest raised on glycogen phosphorylase isoenzyme BB (GPBB) has prompted us to perform a meta-analysis of published studies.

Materials and methods:

A systematic electronic search was carried out on PubMed, Web of Science and Google Scholar, with no date restriction, to retrieve all articles that have investigated the early diagnostic performance of GPBB in patients with suspected AMI, and directly reported or allowed calculation of sensitivity and specificity. A meta-analysis of the reported sensitivity and specificity of each study and pooled area under the curve (AUC) was then performed by random effect approach. Heterogeneity was assessed by I-square statistics.

Results:

Eight studies were finally selected for analysis (941 subjects; 506 cases and 435 controls), with a high heterogeneity (I-squared, 86.3%). The resulting pooled estimates and 95% confidence interval were 0.854 (0.801–0.891) for sensitivity, 0.767 (0.713–0.815) for specificity, 0.826 (0.774–0.870) for negative predictive value, 0.802 (0.754–0.844) for positive predictive value, and 0.754 (0.602–0.907) for AUC. In those studies that have simultaneously assessed GPBB and a troponin immunoassay, the combination of these biomarkers did not significantly improve the performance of troponin alone.

Conclusion:

GPBB does not meet the current requirements for an efficient diagnosis of AMI when used as a stand-alone test, whereas its combination with troponin merits further investigation in larger trials.     

Association of Inflammatory Biomarker C-Reactive Protein, Lipid Peroxidation and Antioxidant Capacity Marker with HbF Level in Sickle Cell Disease Patients from Chattisgarh

This study was undertaken to determine the association of inflammatory biomarker, oxidative stress and antioxidant capacity marker with fetal haemoglobin (HbF) level among sickle cell trait and sickle cell disease (SCD) patients in Chattisgarh. The study group consisted of 51 SCD (SS) patients with painful episode, 49 SCD (SS) patients with steady state, 50 sickle cell trait (AS) and 50 controls. Malondialdehyde (MDA), CRP, total antioxidant power (FARP), total thiol and HbF levels were quantified. We found a significant positive (p < 0.0001) association between CRP and MDA levels and its inverse association with HbF level in SS patients. We also observed that antioxidant capacity had significantly positively (p < 0.0001) associated with HbF level. The protective effect of HbF was found, because the increase in HbF levels resulted in decrease in lipid peroxidation and inflammation in SCD patients. A decrease in the HbF level and its antioxidant capacity has been associated with the pathogenesis of SCD. These finding may explain the high level of HbF is ameliorating oxidative stress and inflammation in SCD patients.     

SXP–RAL Family Filarial Protein,rWbL2, Prevents Development of DSS-Induced Acute Ulcerative Colitis

Helminthic infections lead to the release of various molecules which play an important role in modulation of the host immune system. Such filarial proteins with immunomodulatory potential can be used for therapeutic purpose in inflammatory and immune mediated diseases. In the present study, we have explored the prophylactic effect of filarial SXP–RAL family protein of Wuchereria bancrofti i.e. rWbL2 protein in DSS induced inflammatory ulcerative colitis in a mouse model. Prior treatment of rWbL2, followed by induction of colitis, showed significantly reduced disease severity as indicated by the decreased disease manifestations and improved macroscopic and microscopic inflammation. This preventive effect was found to be associated with increased release of anti-inflammatory cytokine IL-10 and decreased release of proinflammatory cytokines IFN-γ, TNF-α, IL-6 and IL-17 by the splenocytes of treated mice. From this study, it can be envisaged that pretreatment with filarial protein, rWbL2, can prevent the establishment of ulcerative colitis in BALB/c mice. The underlying immunological mechanism may involve the up-regulation of Th2 immune response with down-regulation of Th1 response.     

Diagnostic Potential of Circulating Biomarkers in Adenosine Deaminase Diagnosed Pleural Tuberculosis Cases

Pleural tuberculosis accounts for nearly 20% of Extra pulmonary tuberculosis. Adenosine deaminase, commonly used biomarker for the diagnosis, is non specific and there is paucity of literature on its correlation with conventional or newer methods for the diagnosis of extra pulmonary forms of TB. The aim of the study was to assess diagnostic potential of T cell function markers [interferon (IFN-γ), interleukin (IL-2) and IFN-γ/IL-2 ratio]; macrophage activation marker [neopterin]; and oxidative stress markers [protein carbonyl and malondialdehyde (MDA)] in pleural tuberculosis. 26 pleural TB cases diagnosed on the basis of suggestive chest X-ray and raised serum ADA levels and healthy controls were included in the study. Pleural fluid specimens were subjected to Zeihl Neelsen staining and culture on Lowenstein Jensen medium. Serum IFN-γ, IL-2, neopterin and protein carbonyl levels detection were done by ELISA and MDA levels were determined by measuring the thiobarbituric acid reactive substances. Median serum levels of IFN-γ, IL-2, IFN-γ/IL-2 ratio, neopterin, protein carbonyl and MDA were significantly different between cases and controls. Levels of all biomarkers except IL-2 were significantly higher in cases with contact history. Mean levels of ADA and ESR were 46.27 U/L and 46.62 mm/hr in PTB cases. AUC for IFN-γ, IL-2, IFN-γ/IL-2 ratio, neopterin, protein carbonyl and MDA were significantly discriminative for cases and controls. IFN-γ/IL-2 ratio was best discriminatory biomarker with highest area under ROC curve. Though no correlation was seen between ADA and any of the six biomarkers, ESR levels correlated significantly with all biomarkers except IL-2 by spearman’s correlation coefficient. Though all the circulating biomarkers under study provide useful supportive evidence for the diagnosis of PTB, further studies involving diverse control groups particularly non-PTB effusion are needed to validate these results.     

Serum Cytokine Profile in Psoriasis-A Case–Control Study in a Tertiary Care Hospital from Northern India

Psoriasis is chronic autoimmune hyperproliferative skin disease with a population prevalence of 1.5–3%. The cause of psoriasis is still not fully understood. It has been hypothesized to be an immune-mediated disorder in which the excessive reproduction of keratinocytes is due to cytokines such as interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha, secreted by infiltrating CD4⁺ and CD8⁺ T cells and natural killer cells. The aim of our study was to determine the serum levels of TNF-α, IL-4, IL-6 & IL-10 in psoriasis patients and compare it with healthy controls. 30 clinically diagnosed psoriasis patients and 30 age and sex matched healthy controls were included in the study. The serum cytokine levels were measured by solid phase sandwich ELISA (DIACLONE Research, France). TNF-α and IL-6 levels were significantly raised in patients and the results were statistically significant (P < 0.001). IL-4 levels were higher in patients than in controls (1.91 ± 4.7 pg/ml in cases & 0.9 ± 0.3 pg/ml in controls) but were not statistically significant. Interestingly, IL-10 levels were found to be higher in controls than in patients but again, it was not statistically significant. Pro-inflammatory cytokines play a pivotal role in the pathogenesis of psoriasis and it is the type 1(TH1) cytokine pattern, i.e., IL-6 & TNF-α, which predominate in the psoriatic T cell response. Further studies on IL-10 levels in psoriasis are recommended to establish their exact role in the pathogenesis of the disease.