Inflammatory Cytokines,Apoptotic, Tissue Injury and Remodeling Biomarkers in Children with Congenital Heart Disease

The present study aims to evaluate specific biomarkers involved in congenital heart disease (CHD), and whether there is a significant differences between the levels of these biomarkers in the cyanotic CHD (CCHD) and acyanotic CHD (ACHD). We prospectively measured tumor necrosis factor (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), vasoendothelial growth factor (VEGF), troponin T, creatin kinase MB (CKMB), and Caspase 3 levels in 120 consecutive children with CHD (60 cyanotic and 60 a cyanotic with age 1:4 years), and 30 healthy control children. Significant elevated levels of inflammatory markers; TNF-α, IL-6 and CRP was detected in CHD, with percentage increase in cyanotic than a cyanotic subjects as compared to the normal one. Apoptotic biomarker; caspase 3 showed also significant increases in CCHD than ACHD. In addition, tissue injury mechanisms included troponin T and CKMB, exhibited significant increase in cyanotic than a cyanotic CHD. The present results demonstrate also, significant enhancement in remodeling process (VEGF), in cyanotic than a cyanotic patients. Thus, it could be concluded that, the children with CCHD were shown to have elevated levels of inflammatory cytokines, caspase 3, troponin T, and CKMB as these biomarkers may implicated in cardiac functional status.     

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.     

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.     

Impact of CCL2 and Its Receptor CCR2 Gene Polymorphism in North Indian Population: A Comparative Study in Different Ethnic Groups Worldwide

Chemokine are small, inducible pro-inflammatory cytokines involved in many biological processes, such as migration of leukocytes, atherosclerosis, angiogenesis, tumor growth, and metastasis. Chemokine are also known to influence tumor cell’s activity. Specifically, tumor cells express chemokine receptors in a non random manner suggesting a role of chemokine in metastatic destination of tumor cells. The present study was conducted to determine distribution of (Chemokine receptor 2) CCR2 V64I, Chemokine ligand 2 CCL2 I/D, and CCL2 2518 A>G gene polymorphisms in North Indian population and compare with different populations globally. Polymerase chain reaction (PCR)-based analysis was conducted in 200 normal healthy individuals of similar ethnicity. Allelic frequencies in wild type (GG) of CCR2 V64I G>A were 63 % G; CCL2 I/D 42 % II; CCL2 2518 A>G 40.5 % A. The minor variant allele frequency in our population was as follows: 19.5 % for CCR2 V64I, 35.5 % for CCL2 I/D, 35.3 % for CCL2 2518 A>G. We further compared frequency distribution for these genes with various published studies in different ethnicity. Our results suggested that frequency in chemokine genes exhibit distinctive pattern in India that could be attributed to ethnicity variation. This could assist in high-risk screening of human exposed to environmental carcinogens and cancer predisposition in different ethnic groups. Thus, they signify an impact of ethnicity and provide a basis for future epidemiological and clinical studies.     

Biochemical Effects of Lead Exposure on Systolic &; Diastolic Blood Pressure,Heme Biosynthesis and Hematological Parameters in Automobile Workers of North Karnataka (India)

The purpose of this study was to find out the effect of lead exposure on systolic and diastolic blood pressure, heme biosynthesis related and hematological parameters of automobile workers. For this study 30 automobile workers were selected and compared with 30 age matched healthy control subjects. Significantly increased blood lead (364%, P < 0.001) and urinary lead (176%, P < 0.001) levels were observed in automobile workers (study group) as compared to controls. Systolic blood pressure (5.32%, P < 0.05) and diastolic blood pressure (5.87%, P < 0.05) were significantly increased in the automobile workers as compared to controls. The significantly decreased non-activated erythrocyte δ-aminolevulinic acid dehydratase (δ-ALAD) (−18.51%, P < 0.01) and activated δ-ALAD (−13.29%, P < 0.05) levels were observed in automobile workers as compared to normal healthy control subjects. But the ratio of activated/non-activated δ-ALAD was significantly increased (43.83%, P < 0.001) in automobile workers as compared to controls. Excretions of δ-aminolevulinic acid (83.78%, P < 0.001) and porphobilinogen (37%, P < 0.001) in urine were significantly increased in the study group as compared to the controls. In automobile workers heamoglobin (−11.51%, P < 0.001), hematocrit (−4.06%, P < 0.05), mean corpuscle volume (−3.34%, P < 0.05), mean corpuscle hemoglobin (−5.66%, P < 0.01), mean corpuscle hemoglobin concentration (−7.67%, P < 0.001), red blood cell count (−14.6%, P < 0.001) were significantly decreased and total white blood cell count (11.44%, P < 0.05) increased as compared to the controls. The results of this study clearly indicate that the absorption of lead is more in automobile workers and it affects on blood pressure, heme biosynthesis and hematological parameters observed in this study group.     

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.     

Genetic Polymorphism of Angiotensin II Type 1 Receptors and Their Effect on the Clinical Outcome of Captopril Treatment in Arab Iraqi Patients with Acute Coronary Syndrome (Mid Euphrates)

Genetic variation in the angiotensin II type 1 receptor (AT1R) has an important effect on the outcome of acute coronary syndrome (ACS) initiated treatment with captopril. This study aims to investigate the impact of genetic polymorphism of AT1R (rs5186 and rs275651) on the ACS outcome in Iraqi patients treated with captopril. A total of 250 Iraqi individuals with ACS were included in this case—control study and they were divided into two study groups; Study group 1 included 125 participants who were prescribed captopril, 25 mg twice daily and study group 2 included 125 participants who received no captopril as part of their ACS treatment (control study). The AT1R gene (rs5186) CC genotype was found to be associated with ST-elevation myocardial infarction (STEMI) (Odd’s ratio (O.R) = 1.2, P = 0.7), while AC was associated with Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) (O.R = 1.2, P = 0.8). AC genotype is more prone to have Percutaneous coronary intervention (PCI) after ACS attack (O.R = 1.2, P = 0.6). CC genotype had a risk to get less improvement (O.R = 1.6, P = 0.5), so might require higher doses of captopril during acute coronary insult. The AT1R gene (rs275651) AA genotype was associated with UA (O.R = 1.3, P = 0.9). AA and AT genotypes were more prone to have PCI after ACS attack (O.R = 3.9 P = 0.2, O.R = 3.5, P = 0.3 respectively) and thus requiring higher doses of captopril. We conclude that the AT1R rs5186, rs275651 genetic polymorphisms might partially affect the clinical outcome of ACS patients treated with captopril and might have captopril resistance which requires higher doses.     

Evaluation of Low Blood Lead Levels and Its Association with Oxidative Stress in Pregnant Anemic Women: A Comparative Prospective Study

To correlate blood lead levels (BLLs) and oxidative stress parameters in pregnant anemic women. A total of 175 pregnant women were found suitable and included for this study. Following WHO criteria, 50 each were identified as non-anemic, mild anemic and moderate anemic and 25 were severe anemic. The age of all study subjects ranged from 24–41 years. At admission, BLLs and oxidative stress parameters were estimated as per standard protocols and subjected with ANOVA, Pearson correlation analysis and cluster analysis. Results showed significantly (p < 0.01) high BLLs, zinc protoporphyrin (ZPP), oxidized glutathione (GSSG), lipid peroxide (LPO) levels while low delta aminolevulinic acid dehydratase (δ-ALAD), iron (Fe), selenium (Se), zinc (Zn), haemoglobin (Hb), haematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), red blood cell (RBC) count, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (TAC) in all groups of anemic pregnant women as compared with non anemic pregnant women. In all groups of pregnant women, BLLs showed significant (p < 0.01) and direct association with ZPP, GSSG and LPO while inverse relation with δ-ALAD, Fe, Se, Zn, Hb, Hct, MCV, MCH, MCHC, RBC, GSH, SOD, CAT and TAC. Study concluded that low BLLs perturb oxidant-antioxidant balance and negatively affected hematological parameters which may eventually Pb to Fe deficiency anemia during pregnancy.     

Model-based orbital-scale precipitation δ18O variations and distinct mechanisms in Asian monsoon and arid regions

The past Asian precipitation δ¹⁸O (δ¹⁸O_p) records from stalagmites and other deposits have shown significant orbital-scale variations, but their climatic implications and regional differences are still not fully understood. This study, as the first attempt of a 300-kyr transient stable isotope-enabled simulation, investigated the characteristics and mechanisms of the orbital-scale δ¹⁸O_p variations in three representative regions of Asia: arid Central Asia (CA), monsoonal South Asia (SA) and monsoonal East Asia (EA). The modelling results showed that the variations in the CA, SA and EA annual δ¹⁸O_p exhibited significant but asynchronous 23-kyr precession cycles. Further analyses revealed that although the precession-induced insolation variation was the ultimate cause of the δ¹⁸O_p variation in all three regions, the dominant mechanisms and the involved physical processes were distinct among them. For the CA region, the rainy-season (November–March) temperature effect and water vapour transport by the westerly circulation were identified as the key precession-scale processes linking the October–February boreal mid-latitude insolation to the rainy-season or annual δ¹⁸O_p. In the SA region, the rainy-season (June–September) precipitation amount effect and upstream depletion of the monsoonal water vapour δ¹⁸O served as the main mechanisms linking the rainy-season or annual δ¹⁸O_p to the April–July insolation variation at the precession scale. For the EA region, however, the precession-scale annual δ¹⁸O_p was mainly controlled by the late-monsoon (August–September) and pre-monsoon (April–May) water vapour transport patterns, which were driven by the July–August insolation and the global ice volume, respectively. These results suggest that the climatic implications of the orbital-scale Asia δ¹⁸O_p variations are sensitive to their geographic locations as determined by the combined effects of insolation and regional circulation patterns associated with the respective rainy seasons. This study provides new insights into understanding the regional differences and formation mechanisms of the Asian orbital-scale δ¹⁸O_p variations.     

Interplay Between Inflammation and Hemostasis in Patients with Coronary Artery Disease

Coronary artery disease (CAD) is a global epidemic currently. This study was planned to evaluate markers of inflammation and hemostasis and their possible association, if any, in patients with CAD. The study was carried out in 60 patients with acute myocardial infarction (AMI) and 60 age and gender matched controls. The following parameters were assayed in all study subjects-inflammatory-interleukin (IL)-10, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, fibrinogen; hemostatic-fibrinogen, fibrin D-dimer and a novel risk factor—homocysteine. Inflammatory markers (hs-CRP, TNF-α and IL-10), fibrinogen, fibrin D-dimer and homocysteine levels were significantly higher in the patients with AMI, as compared with controls. A positive correlation was observed between D-dimer and the inflammatory markers—hs-CRP and TNF-α. Upon multivariate analysis, TNF-α emerged as the best determinant of CAD in our study. Our results indicate that there is a possible interplay of inflammation and hemostasis in CAD, underlining their synergistic role in the pathogenesis of CAD.