Involvement of Depressive Catecholamines as Thrombosis Risk/Inflammatory Markers in Non-Smoker,Non-Obese Congestive Heart Failure,Linked to Increased Epidermal Growth Factor-Receptor (EGF-R) Production

The EGF-R, also known as HER-1 or erbB-1 (EGF-R/HER-1/erbB-1), is a member of the human epithelial receptor tyrosine kinase family. sEGF-R is considered to play a role in cardiac (patho)physiology. We aimed to investigate whether soluble EGF-R is increased in congestive heart failure (CHF) patients and if related to disease severity. Soluble EGF-R, vitamin D, parathyroid hormone (PTH) was studied, and being evaluated in relation to Ca²⁺, lipids, hsCRP, fibrinogen, serotonin, norepinepherine (NE). The study compared non-smoker, non-obese male CHF patients (n = 50) with age and gender-matched essential hypertension (HTN) patients (n = 20). Moreover, comparison with healthy control volunteers (n = 20) were employed. EGF-R/HER-1/erbB-1 was higher (P = 0.013) in 50 CHF male patients mean 12 ± 0.7 fmol/ml, than in 20 HTN, 9.25 ± 0.6 fmol/ml or in 20 controls, 6.25 ± 1 fmol/ml. Serum EGF-R levels correlated positively with hsCRP and NE, and were highest among CVD patients (n = 70) as well as negatively with vitamin D and HDL-C. EGF-R/HER-1/erbB-1 levels are increased in HTN and more in CHF patients. This study confirms a strong association between catecholamines as well as EGF-R/HER-1/erbB-1 levels with PTH and low vitamin D levels, being related to hyperlipidemia and inflammation (hsCRP and fibrinogen) in CVD. Moreover, contributing to the complex process of the inflammatory component of atherosclerosis in hypertensive patients that leads eventually to CHF.     

Serum Cystatin C Levels in Renal Transplant Recipients

Cystatin C is an emerging parameter for the assessment of renal allograft function. The objective of the study was to compare the efficacy of serum cystatin C (SCys) with the established parameter serum creatinine (SCr) in the assessment of renal function in renal transplant recipients (RTR). The glomerular filtration rate (GFR) of 30 renal transplant patients and 29 control subjects was determined using ^99mTc Diethylene-triamine-penta-acetate (DTPA) method. SCr was measured using an automated Jaffe’s assay and SCys was measured using latex particle enhanced turbidimetric immuno assay (PETIA). The modification of diet in renal disease (MDRD) formula was used to calculate GFR from SCr, while the Le Bricon formula was used to derive GFR based on SCys. Statistical analysis was performed using MedCalc software. SCr and SCys levels were significantly higher, while DTPA clearance was significantly lower in RTR (P < 0.0001) when compared with controls. The correlation coefficient (r value) between calculated GFR based on MDRD method and DTPA clearance was 0.343 (P = 0.06) while the calculated GFR based on Le Bricon formula was 0.694 (P < 0.001). The results have shown that SCys is a better parameter than SCr in assessing renal function in RTR. The inclusion of SCys as an additional parameter would certainly help in detection of even a marginal decline in renal function and also in adjusting the dosage of immunosuppressive drugs.     

Protective Role of Bilirubin Against Increase in hsCRP in Different Stages of Hypothyroidism

In conjunction with thyroxine, bilirubin may play an important role for regulation of hsCRP level and a consequent pro-inflammatory condition in hypothyroidism. In present study we evaluated the dependence of hsCRP changes on total bilirubin (BT) and fT4 level in thirty overt (OH) and thirty subclinical hypothyroidism (SH). Serum BT, hsCRP, thyroxine and TSH were measured in both groups and compared with forty control subjects. Serum values of TSH, hsCRP showed raised (P < 0.001 for both) values with lower levels for fT4 and BT (P < 0.001 and 0.03 respectively) in hypothyroid patients compared to the controls. ANOVA showed significant increments in TSH and hsCRP values with decreases in fT4 among the control, SH and OH groups respectively (P < 0.001). BT values showed decrease in OH group only in comparison to controls (P = 0.04). Regression analysis revealed that hsCRP was negatively dependent on fT4 (β = −0.35, P = 0.002) and serum bilirubin (β = −0.40 and P < 0.001 respectively). Univariate general linear model analysis showed this dependence persisted even when carried out distinctly in SH and OH groups separately (P < 0.001). TSH did not show any significant predictive value on the hsCRP level in either of these two tests. From these analyses we suggest that serum hsCRP is closely integrated to a lowered synthesis of bilirubin and fT4 in hypothyroid patients. Furthermore, this causal relationship is not only limited to overt but also extends to the SH.     

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.     

Study of C-Reactive Protein and Myocardial Infarction in the Indian Population

To analyse the association of high sensitivity C-reactive (hsCRP) protein levels and −717A/G single nucleotide polymorphism of CRP with acute myocardial infarction (AMI) in the Indian population. Study population included 100 MI cases wherein 32 patients had experienced previous MI (MI-Group-1), 68 MI cases were recruited at presentation (MI-Group-2) and equal number of age and gender matched healthy individuals. hsCRP levels were determined by ELISA and genotyping of −717A/G was carried out by polymerase chain reaction-based restriction digestion method. The −717A/G genotypes did not influence hsCRP level and their distribution did not differ between groups. However, in the present study hsCRP demonstrated significant correlation with BMI in controls of both the genders and with triglycerides in females of AMI at presentation who otherwise are with low risk profile. Identifying traditional risk factors associated with inflammation may help in controlling the acute event.     

Myeloperoxidase in Chronic Kidney Disease

Numerous lines of evidence implicate a role of myeloperoxidase (MPO) in the pathogenesis of cardiovascular disease (CVD). It is a well accepted fact that patients with chronic kidney disease (CKD) are at an increased risk for CVD. MPO is a pro-oxidant enzyme which could be involved in the increased susceptibility of these patients to CVD. Hence, the levels of plasma MPO was determined in healthy controls as well as in patients with CKD [stratified with the level of their kidney failure as CKD stages II–V (end stage renal disease)]. Plasma MPO was assayed by a spectrophotometric method. Serum urea and creatinine were estimated on a clinical chemistry analyzer using standard laboratory procedures. The mean plasma MPO levels were significantly lower with advancing stages of renal failure (P < 0.001). There was a positive correlation between MPO and GFR (r = +0.89, P < 0.001) and a negative correlation with urea (r = −0.85, P < 0.001) and creatinine (r = −0.82, P < 0.001). While an inverse association was observed between plasma MPO and urea in CKD patients, such an association was not observed in control subjects (P = 0.43). In conclusion, the decline in plasma MPO levels may be due to the inhibitory effect of uraemic toxins on the enzyme.     

Evaluation of Oxidative Stress and hsCRP in Polycystic Ovarian Syndrome in a Tertiary Care Hospital

PCOS is a heterogeneous endocrine disorder with diverse clinical presentation. Oxidative stress plays a key role in the pathophysiology of this disease. Serumhigh sensitive C-reactive protein (hsCRP), a marker of chronic low grade inflammation, is indicative of future development of cardiovascular disease. Our aim is to evaluate the oxidant status and hsCRP levels in PCOS. The study involved 61 cases and 61 controls in the age group of 18–40 years diagnosed with PCOS. Erythrocyte malondialdehyde (MDA), superoxide dismutase (SOD), serum hsCRP, gonadotrophins, thyroid stimulating hormone, prolactin, glycemic status and lipid profile were estimated. Erythrocyte MDA (p < 0.001), SOD (p = 0.007) and serum hsCRP (p < 0.001) were significantly elevated in PCOS patients than controls. Oxidative stress is present in women with PCOS along with elevated hsCRP.     

Correlation between serum lipid profile and carotid intima-media thickness in Polycystic Ovarian Syndrome

Abnormal lipid profile is often found in women with Polycystic Ovary Syndrome. To assess the impact of abnormal lipid profile on atherosclerosis in young Polycystic Ovary Syndrome women, carotid intima-media thickness as judged by B-mode ultrasonography were done in 30 young (18–35 yrs) Polycystic Ovary Syndrome women and in similarly age-matched 30 apparently healthy controls. Compared to controls, young Polycystic Ovary Syndrome women had significantly elevated serum total cholesterol, triglyceride and LDL-C levels and carotid intima-media thickness. HDL-C level did not differ significantly between two groups of women. In Polycystic Ovary Syndrome women carotid intima-media thickness was positively correlated with serum total cholesterol, triglyceride and LDL-C and negatively correlated with serum HDL-C. Our study suggests that even young Polycystic Ovary Syndrome women are prone to atherosclerosis from early age.     

Adiponectin Gene Polymorphism and its Association with Type 2 Diabetes Mellitus

Mutations in different regions of adiponectin gene have been reported to be associated with obesity, atherosclerosis and type 2 diabetes mellitus. The present study was aimed to investigate the association among SNP 45 T > G of adiponectin gene and type 2 diabetes in South Indian population. 75 clinically diagnosed case of type 2 diabetes were studied and compared with 75 apparently healthy controls. The genotype frequency of SNP45 T > G in exon 2 of adiponectin gene was determined by PCR based restriction enzyme analysis using the restriction enzyme SmaI. (recognition site: CCC↓GGG). Three kind of genotypes: wild type TT (470 bp), heterozygous type TG (470 bp, 336 bp, 134 bp) and homozygote mutant type GG (336 bp, 134 bp) were studied. A positive association has been found between SNP45 T > G and type 2 diabetes in the study population (P = 0.010, OR = 3.797, 95% CI = 1.312–10.983). Therefore, SNP45T > G in adiponectin gene may be one of the risk factors for type 2 diabetes.     

Acid Phosphatase as a Marker in Malaria

The serum acid phosphatase (ACP) activity and Hemoglobin (Hb) levels were measured in malaria patients and nonmalarial fever patients. The results were compared with normal healthy control subjects. ACP was significantly increased (P < 0.001) in all the malaria patients. ACP was significantly higher in Plasmodium falcifarum malaria and mixed malaria when compared to Plasmodium vivax malaria. Hb levels were significantly decreased in all the malaria patients which indicates that malaria parasite uses host erythrocyte Hb as a major nutrient source. There is negative correlation(r = −0.478) between ACP and Hb in malaria patients, which is highly significant. These results suggest that the measurement of ACP could be used as a marker for malaria.     

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.     

Effect of Metformin on Hormonal and Biochemical Profile in PCOS Before and After Therapy

Insulin resistance and the resultant hyperinsulinemia exacerbate the reproductive abnormalities of Polycystic Ovarian Syndrome by increasing ovarian androgen productions and decreasing serum sex hormone binding globulin. The present study was conducted to estimate serum insulin and testosterone level in 44 PCOS cases and 32 control patients. Simultaneously the role of metformin (an insulin sensitizing agent) in modulating insulin resistance and serum androgen level was also analyzed. A significant rise in serum insulin and testosterone (P < 0.001) was observed in cases in comparison to control. Fasting Plasma Glucose to insulin ratio, a marker of insulin resistance revealed a significant fall in PCOS group. Follow up of cases with metformin for 3 months revealed a significant fall in serum insulin (P < 0.05) with improvement in insulin resistance along with a nonsignificant fall in testosterone level. Serum insulin registered a significant positive correlation (P < 0.05) with serum testosterone revealing its etiological association. Thus administration of drugs ameliorating insulin levels is expected to provide new therapeutic modality for PCOS.     

Homocysteine status and acute myocardial infarction among Tamilians

Myocardial infarction is a major consequence of coronary artery disease. Apart from the traditional risk factors of myocardial infarction, recently many reports have suggested that hyperhomocysteinemia plays important role in myocardial infarction. Plasma homocysteine level was determined in 60 myocardial infarction patients and in 35 age matched healthy individuals. Statistically significant differences (p<0.01) were observed in the mean of plasma homocysteine concentrations between the acute myocardial infarction patients (24.59±6.14 mM/L) and in normal healthy individuals (13.73 ±3.54 mM/L). The level of homocysteine in myocardial infarction patients is significantly high (p <0.01) among myocardial infarction patients when compared to that of the controls. The the present study indicates a strong association between plasma homocysteine and acute myocardial infarction among Tamilians, thus implying plasma homocysteine as a possible risk factor for myocardial infarction.     

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.     

Anti-Oxidative Effect of <Emphasis Type="Italic">Cassia auriculata</Emphasis> on Streptozotocin Induced Diabetic Rats

The anti oxidative effect of administration of 100 mg/kg bw and 200 mg/kg bw of the flower powder of Cassia auriculata (CFP) for 45 days to normoglycemic and diabetic rats (streptozotocin induced) was studied. Anti oxidative effect was not observed in normoglycemic rats in the experiment. There was significant (P > 0.05) increase in the level of Thio Barbituric Acid Reactive Substances (TBARS), hydroperoxide and conjugated dienes and significant (P > 0.05) decrease in the catalase, superoxide dismutase and glutathione peroxidase activities and in the level of ascorbic acid, vitamin E and reduced glutathione in diabetic rats. The flower powder of Cassia auriculata significantly (P > 0.05) decreased the TBARS, hydroperoxide and conjugated dienes and increased the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and non enzymic anti oxidants (ascorbic acid, vitamin E and reduced glutathione). The antioxidatve effect of 200 mg/kg bw CFP was significantly (P > 0.05) better than 100 mg/kg bw CFP and the reference drugs (tolbutamide and metformin). The mode of action of CFP remains to be elicited.     

Role of l-Arginine on Dyslipidemic Conditions of Acute Myocardial Infarction Patients

Oxidative stress conditions associated with atherosclerosis leads to oxidative modification of low-density lipoprotein (LDL). The body’s capabilities to inhibit LDL oxidation and to remove or neutralize the atherogenic oxidized LDL (ox-LDL) are limited. When the LDL cholesterol level increases in the blood, it leads to dangerous consequences like atherosclerosis, leading to myocardial infarction. The major effect of an antioxidant in the LDL environment is to prevent the formation of ox-LDL (during atherogenesis. Strategies to reduce LDL oxidation and prevent atherogenesis can involve the enrichment of arterial cells with potent antioxidants that can prevent oxidative damage to the arterial wall. The objective of this study is to evaluate the effect of l-arginine on serum lipid and cholesterol levels in the patients of acute myocardial infarction (AMI). The study consisted of 70 AMI patients and 60 healthy individuals (serving as control) age 55–65 years. Serum levels of total cholesterol, high density lipoprotein (HDL), LDL and Triglycerides were determined on day 1 and day 15 of l-arginine administration (oral dose 3 g/day). The total cholesterol/HDL and the LDL/HDL ratio were calculated and compared. As per the observations, l-arginine administration was found to improve the lipid profile of the subjects. Hence it could be used as an adjuvant therapy for AMI and as a preventive measure for the onset of the disease in the healthy elderly also.     

Serum Paraoxonase (PON1) Activity in North-West Indian Punjabi’s with Acute Myocardial Infarction

Human serum paraoxonase-1 (PON1), an enzyme on HDL prevents oxidation of LDL thereby preventing the development of atherosclerosis. Studies done so far have lead to conflicting results. As studies are lacking in North-West Indian Punjabi’s, a distinct ethnic group with high incidence of coronary artery disease, we determined PONase activity in this population. It has been postulated that sudden lowering of serum PONase may lead to precipitation of acute myocardial infarction. We determined serum PONase activity and lipids in 100 patients each of AMI (within 24 h of onset), stable CAD and 100 age and sex matched healthy controls. These were again determined after 6 weeks in AMI patients. The mean serum PONase activity was lowest in AMI patients (23.26 U/ml) followed by stable CAD patients (102.0 U/ml) where as in controls was highest (179.8 U/ml). In patients with AMI, activity was significantly higher at 6 weeks as compared to that after acute event (49.39 %; p < 0.05). Sudden lowering of serum PONase activity in a population which already has lower activity may be one of the risk factors for development of AMI.     

Correlation of Adiponectin and Leptin with Insulin Resistance: A Pilot Study in Healthy North Indian Population

The increasing incidence of obesity, leading to metabolic complications is now recognized as a major public-health problem. Insulin resistance is a central abnormality of the metabolic syndrome, or syndrome X, originally hypothesized by Reaven Insulin resistance is more strongly linked to intra abdominal fat than to fat in other depots. Adipose tissue secretes numerous factors (adipokines) known to markedly influence lipid and glucose/insulin metabolism, oxidative stress, and cardiovascular integrity. Some of these adipokines have been shown to directly or indirectly affect insulin sensitivity through modulation of insulin signaling and the molecules involved in glucose and lipid metabolism. A pilot study was conducted with 80 healthy subjects who were non diabetic, non hypertensive and having no family history of hypertension, the aim was to evaluate the correlation of adiponectin and leptin levels with obesity and insulin resistance markers in healthy north Indian adult population. Serum leptin, adiponectin and insulin was estimated by sandwich ELISA method. In our study, Leptin correlated significantly with BMI (P value of 0.0000), WC (P value = 0.007), and HC (P value = 0.000). leptin showed significant positive correlation with fasting insulin (P value 0.002), post prandial insulin (P value = 0.000) and HOMA-IR (P value = 0.002). Adiponectin showed significant positive correlation with triglycerides (P value = 0.038), strong negative correlation with HDL-cholesterol (P value = 0.017). Serum concentrations of leptin are associated with central body fat distribution. Insulin resistance and adiponectin is associated with dyslipidemia and these all disorders may ultimately lead to metabolic syndrome.     

BMD and Serum Intact Osteocalcin in Postmenopausal Osteoporosis Women

India seems to have the highest prevalence of osteoporosis. With growing awareness of osteoporosis and its impact on life span especially in India, special attention is being paid to early detection, management and treatment of postmenopausal osteoporosis in women. Measurement of BMD and osteocalcin are of value in estimating bone turnover rates. The aim of this study is (1) to measure the specific, sensitive bone formation marker such as osteocalcin and BMD in postmenopausal osteoporosis women and postmenopausal non-osteoporosis women; (2) the follow up study to evaluate the impact of specific antiresorptive therapy (alendronate + calcium + vitamin D) regimen in postmenopausal osteoporosis by assaying osteocalcin and BMD. Sixty clinically diagnosed postmenopausal osteoporosis patients and 60 normal subjects (postmenopausal non-osteoporosis women) were recruited as control. Mean bone mineral density T score and Z score was significantly decreased (P < 0.001) in postmenopausal osteoporosis patients as compared to controls. Highly significant increase in the mean score of BMD—T score and Z score from baseline to post therapy of 3 months was observed in postmenopausal osteoporosis women. Serum osteocalcin levels were significantly increased (P < 0.001) as compared to control group. Serum osteocalcin levels were decreased significantly (P < 0.001) from baseline to post therapy of 3 months in postmenopausal osteoporosis women. BMD is the best quantifiable predictor of osteoporotic fracture and osteocalcin is specific, sensitive, promising, currently used marker for better prognosis of osteoporosis and for monitoring responses to antiresorptive therapy.     

Study of Oxidative Stress in Vitiligo

Vitiligo is an idiopathic, acquired, circumscribed, hypomelanotic skin disorder, characterized by milky white patches of different sizes and shapes. It is due to the destruction of melanocytes resulting in the absence of pigment production of the skin and mucosal surfaces. Oxidative stress has been implicated in pathophysiology of vitiligo. To study the activity of blood Superoxide dismutase (SOD) and Glutathione peroxidase (GPx) in vitiligo patients. A case–control study was conducted in which 100 patients were enrolled after written consent. 50 cases were of active vitiligo and 50 served as control (25 healthy control and 25 with stable vitiligo). SOD—In our study, among the active vitiligo cases 90% had high level of SOD and 10% had normal level of SOD. Among the stable vitiligo controls, 92% had normal level of SOD and 8% had low levels of SOD.The difference between active vitiligo cases and stable vitiligo control as well as with healthy control was statistically significant (P value < 0.05). GPx—Among the active vitiligo cases 74% had normal GPx levels, 22% had low and only 4% had high levels of GPx. Among the stable vitiligo controls, 64% had normal GPx levels, 16% had low, and 20% had high levels of GPx. The difference between active vitiligo cases and stable vitiligo control as well as with healthy control was statistically not significant (P value > 0.05). Our study shows that oxidative stress is involved in the pathophysiology of vitiligo, as indicated by the high levels of serum superoxide dismutase activity.