L. M. Srivastava

Expression of complement regulatory proteins in diffuse proliferative glomerulonephritis.

This study assessed the expression of complement receptor 1 (CR1), decay accelerating factor (DAF) and membrane inhibitor of reactive lysis (CD59) on the erythrocytes and glomerulus of diffuse proliferative glomerulonephritis (DPGN) of systemic lupus erythematosus (SLE) patients using flow cytometry and immunofluorescence techniques to elucidate their role in the pathogenesis of DPGN. Expression of CR1 on the erythrocytes and glomerulus of DPGN patients was reduced compared with expression in normal subjects. However, expression of DAF and CD59 was increased on both erythrocytes and glomerulus of DPGN patients, suggesting the generation of a protective response against complement-mediated injury.

Apolipoprotein E polymorphism in Northern Indian patients with coronary heart disease: phenotype distribution and relation to serum lipids and lipoproteins.

Apolipoprotein E (apo E), a genetic determinant of plasma lipid levels and coronary heart disease (CHD) needs to be investigated in Asian Indians since they have a propensity to develop dyslipidemia and accelerated atherosclerosis. We studied apo E phenotypes and plasma lipid levels in 52 Northern Indian male patients (aged 38–71 years) with angiographically proven CHD, and compared them to 50 healthy blood donors taken as the control group. High levels of Lp(a), (p < 0.05), and a definite trend towards lower levels of HDL-C (p < 0.05), was observed in the CHD patients as compared to the control subjects. The frequency of apo E allele ε3 was 0.86 and 0.862, and ε4 allele was 0.12 and 0.08 in the patients and controls, respectively. However, a lower frequency of the E2 allele was observed in the patient group (ε2 = 0.02) as compared to the controls (ε2 = 0.06) (p = ns). In individuals with apo E3/E3 phenotype, significantly lower HDL-C levels was observed in the CHD patients as compared to the control subjects (p < 0.05). A positive correlation was observed between apo E phenotypes and Lp(a) levels in the CHD subjects as compared to the controls (p < 0.05), the level being significantly high in CHD subjects with at least one E4 allele. To conclude, in this sample of Northern Indian subjects with CHD, there is a significant correlation between apo E3/E3 phenotype and low levels of HDL-C as compared to the control subjects. Further, apo E phenotype is positively correlated with high Lp(a) levels in the CHD subjects having at least one E4 allele. However, these relationships need to be explored in a larger sample of subjects.

Procalcitonin as a rapid diagnostic biomarker to differentiate between culture-negative bacterial sepsis and systemic inflammatory response syndrome: A prospective, observational, cohort study☆

PURPOSE Differentiation between culture-negative sepsis and noninfectious systemic inflammatory response syndrome (SIRS) remains a diagnostic challenge for clinicians, both conditions having similar clinical presentations. Therefore, a swift accurate diagnostic tool, which helps differentiate these 2 conditions would immensely aid appropriate therapeutic continuum. This prospective study was conducted to evaluate the potential diagnostic role of biomarkers, procalcitonin (PCT) and interleukin 6 (IL-6), in culture-negative sepsis patients. METHODS Enrolled patients (208) included 46 noninfectious SIRS, 90 culture-negative sepsis, and 72 culture-positive sepsis. Culture, PCT, and IL-6 estimations were performed on day 1 of intensive care unit admission. RESULTS Procalcitonin and IL-6 levels were significantly higher (P < .001) in both culture-negative and culture-positive groups as compared with SIRS group. Procalcitonin was a better predictor of sepsis in both culture-negative (area under curves 0.892 vs 0.636) and culture-positive (area under curves 0.959 vs 0.784) groups as compared with IL-6. In culture-negative group, the best cutoff point for PCT was at 1.43 ng/mL (92% sensitivity; 83% negative predictive value), best cutoff point for IL-6 was at 219.85 pg/mL (47% sensitivity and 42% negative predictive value). CONCLUSIONS Procalcitonin can accurately differentiate culture-negative sepsis from noninfectious SIRS and thereby contribute to early diagnosis and effective management of these conditions.

Prevalence of Hyperhomocysteinemia in Vascular Disease: Comparative Study of Thrombotic Venous Disease Vis-è-Vis Occlusive Arterial Disease

Studies on hyperhomocysteinemia in vascular occlusive disease have included mostly patients with arterial occlusion. However, more recent studies have included cases of venous occlusive disease as well. Our present study is aimed at comparing the prevalence of hyperhomocysteinemia in venous occlusive disease vis-è-vis arterial occlusive disease in the North Indian urban population. Homocysteine was estimated by chemiluminescent immunoassay in 205 normal controls and 536 patients, 244 presenting with arterial occlusion and 292 with venous thrombotic disease. The mean homocysteine in patients with arterial occlusion was 21.79 ± 0.09 μmol/L (mean ± standard error of measurement), in patients with venous thrombosis was 25.53 ± 0.1 μmol/L, and in controls was 11.33 ± 0.18 μmol/L. The prevalence of hyperhomocysteinemia (> 15 μmol/L) was 56.38% in arterial occlusive disease and 54.64% in venous thrombosis. In patients with peripheral vascular occlusive disease, patients with deep venous thrombosis (DVT) had the highest mean homocysteine level (25.51 μmol/L), which was even higher (32.14 μmol/L) when associated with pulmonary embolism (PE). There is a high prevalence of hyperhomocysteinemia in arterial and venous occlusive disease. Hence, in all patients with vascular occlusive disease, hyperhomocysteinemia should be elucidated and treated. In addition, long-term follow-up is required to ascertain whether the reduction in homocysteine decreases the thrombotic events and whether homocysteine levels can actually be of prognostic or predictive value in cases of DVT with PE.

Lowered expression of C3b receptor (CR1) on erythrocytes of rheumatoid arthritis patients

The number of C3b receptors (CR1) on erythrocytes (E) has been quantitated by whole cell enzyme-linked immunosorbent assay (ELISA), using a monoclonal anti-CR1 antibody, in 46 healthy individuals as controls, 58 having rheumatoid arthritis (RA) and 3 hereditary angioedema patients. The mean value of CR1 in RA (381/E) was significantly lower (p < 0.001) when compared to normal controls (646/E). In hereditary angioedema patients CR1 numbers (620/E) were found to be comparable to normal values. No significant difference was found between normal male (708/E) and female (598/E) subjects. Among the patient groups, those on steroid therapy (352/E) showed no change compared to others not receiving such therapy (408/E). The cumulative frequency curve of CR1 in the normal population showed maximum inflection at 32% and 82%. This led us to conclude that there is a trimodal distribution of receptors in the control population. Such a contention is well supported by frequency histogram, when a small group interval (0-50) was chosen. However, if large group intervals (0-100 or 0-150) were considered, a very close approximation to unimodal pattern was obtained. The factors actually contributing to low receptor numbers are yet to be elucidated.

Apolipoprotein C3 SstI polymorphism in the risk assessment of CAD

Various population studies have reported the association of rare S2 allele of apolipoprotein C3 (APOC3) SstI polymorphism with hypertriglyceridemia (HTG) and coronary artery disease (CAD). We were the first to report an association of S2 allele with high triglyceride (TG) levels in healthy volunteers from Northern India. Since HTG is suggested to be a predominant risk factor for CAD among Indians, we have elucidated the relationship of APOC3 SstI polymorphism with the lipid profile and CAD. A total of 158 patients with ≥ 70% stenosis in one or more coronary artery (angiographically proven CAD patients), 35 subjects with < 70% stenosis (NCAD) and 151 normal controls (free of heart disease) from Northern plains of India were recruited in the study. DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Lipid profile was estimated by enzymatic kit. We found a strong association of S2 allele with high TG levels, which was more significant in patients. Prevalence of S2 allele in normal controls and CAD patients were comparable, despite the fact that mean TG level was significantly higher in patients. A greater insight into this observation revealed that the prevalence of high TG, if not coupled with other risk factors (like high total cholesterol, low HDL), was comparable in patients and controls. Thus, our study reveals that rare S2 allele may be employed as a susceptibility marker for high TG. However, high TG or S2 allele alone may not contribute to the etiology of CAD.

Effect of ascorbic acid on lipid profile and lipid peroxidation in hypercholesterolemic rabbits

Abstract Four groups of rabbits were studied for 6, 10, and 16 weeks to determine the effect of ascorbic acid on cholesterol induced hypercholesterolemia. Serum concentrations of triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C) and malondialdehyde (MDA) were studied. TC, LDL-C and VLDL-C increased significantly in cholesterol fed rabbits whereas in cholesterol and ascorbic acid fed rabbits, the increase was significant but less than the previous group, in comparision to controls. The MDA level increased by 16% after 16 weeks in cholesterol fed groups whereas in cholesterol and ascorbic acid fed groups the MDA level was normal. The results indicate that ascorbic acid administration reduces the development of hypercholesterolemia in rabbits through its antioxidant property.

Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p < 0.001). This suggests that use of ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

Lowering homocysteine and modifying nutritional status with folic acid and vitamin B12 in Indian patients of vascular disease

Hyperhomocysteinemia is more commonly associated with vascular disease in Indians than in the western populations. It is caused by genetic polymorphisms or dietary deficiencies of the B vitamins. We attempted to identify the association of hyperhomocysteinemia with vitamin B12 and folate in Indian patients of vascular disease. Homocysteine, vitamin B12 and folate levels were estimated in 100 controls and 100 patients of vascular disease. Homocysteine estimation was repeated in 73 patients on different vitamin supplements for 6 months. Homocysteine exhibited a significant negative correlation with B12 only in cerebrovascular disease and peripheral vascular diseasepatients, and with folate in coronary artery disease and cerebrovascular disease patients as well as controls. Single daily dose of folate was as effective as a combination of folate and cobalamin in reducing plasma homocysteine concentrations. Low levels of B12 contribute to the higher incidence of cerebrovascular disease and peripheral vascular disease, and low folate levels account for higher prevalence of hyperhomocysteinemia in coronary artery disease and cerebrovascular disease. Moreover, irrespective of the cause of hyperhomocysteinemia, folate is known to ameliorate it. Hence, large-scale corrective measures like food fortification or dietary supplementation with folate might benefit the Indian population and reduce the incidence and morbidity of vascular disease.

Complement-regulatory protein expression and activation of complement cascade on erythrocytes from patients with rheumatoid arthritis (RA)

It has been previously reported that the expression of the complement receptor, CR1, on erythrocytes is reduced in patients with RA and that the reduced expression of CR1 is related to disease activity. In this study we investigate the role of other regulatory proteins, i.e. decay‐accelerating factor (DAF) and CD59 (membrane inhibitor of reactive lysis), in the pathogenesis of RA by checking the expression of DAF and CD59 on erythrocytes of RA patients to establish whether reduced expression of DAF and CD59 on erythrocytes could be related to increased ability of erythrocytes to activate complement in RA. Flow cytometry was used to measure the expression of DAF and CD59 on erythrocytes from RA patients as well as the deposition of C3 fragments occurring in vivo or after in vitro complement activation. Significantly reduced expression of DAF and CD59 was observed on erythrocytes of RA patients. A significant inverse relationship was observed between DAF expression and in vitro complement activation, whereas no significant relationship between CD59 and complement activation was observed. Finally, we demonstrated an inverse relationship between CH50 activity and DAF expression. Thus, determination of DAF on erythrocytes can emerge as an additional tool in the assessment of extent of complement activation in RA.