Plasma proteinase inhibitory activity in ectopic and molar pregnancy

Antitryptic, antichymotryptic and alpha 2- macroglobulin activities were measured in sera of normal nonpregnant and normal pregnant women and women with tubal ectopic pregnancy and molar pregnancies in the first 5 to 7 weeks of pregnancy calculated from the last menstrual period. While alpha 2-macroglobulin decreased in early normal pregnancy compared to nonpregnant state (p<0.001), in ectopic and molar pregnancies there was an increase in alpha 2- macroglobulin activity (p < 0.001), as compared to nonpregnant and normal pregnant women. Antitryptic activity did not increase in normal and ectopic pregnancy, however was increased in molar pregnancy (p < 0.01). Antichymotryptic activities did not show a change either in normal pregnancy or in cases of ectopic and molar pregnancy. Drop in alpha 2- macroglobulin activity to near normal levels in ectopic, 6 weeks post surgery, correlated well with the decrease in β-hCG. However, in molar pregnancy, alpha 2- macroglobulin remained elevated even when the β-hCG levels in serum returned to zero 10 weeks after surgery. The studies suggest a major role for circulating proteinase inhibitors especially alpha 2-macroglobulin in regulating proteinase activity in normal, ectopic and molar pregnancy.     

Acute Renal Failure in Liver Transplant Patients: Indian Study

The acute renal failure is the frequent medical complication observed in liver transplant patients. The objective of this study was to determine the cause of acute renal failure in post liver transplant patients. A total of 70 patients who underwent (cadaveric 52, live 18) liver transplantation were categorized based on clinical presentation into two groups, namely hepatorenal failure (HRF, n = 29), and Hepatic failure (HF, n = 41). All the patients after the liver transplant had received tacrolimus, mycophenolate and steroids. We analyzed the modification of diet in renal disease, (MDRD) serum urea, creatinine and albumin before and after 5th and 30th day of liver transplant and data was categorized into survivors and non-survivors group. In HRF survivor group, serum creatinine, and urea levels were high and, albumin, MDRD were low in pre- transplant and reached to normal levels on 30th day of post transplant, and 79.3 % of patients in this group showed resumption of normal kidney function. On the contrary in HRF nonsurvivor group, we did not observed any significant difference and 20.7 % of patients showed irreversible changes after the liver transplant. In HF survivor group, 82.9 % of liver failure patients did not show any deviation in serum creatinine, urea, albumin and MDRD, whereas in HF non survivor group, 17.1 % of liver failure patients who had HCV positive before the transplant developed acute renal failure. The levels of creatinine, urea, albumin and MDRD were normal before the transplant and on day 30th, the levels of albumin and MDRD were significantly low whereas serum urea, creatinine levels were high. In conclusion, based on these observations, an diagnosis and treatment of Acute renal failure is important among the liver transplantation cases in the early postoperative period.     

Thyroid hormone profile in peritransplant period in live donor kidney transplantation

Chronic renal failure, characterised by two factors acting in opposite directions with respect to the serum thyroid homone levels was chosen for the study. Healthy controls, donors undergoing nephrectomy and renal transplant recipients were studied. In transplant recipients, presurgical levels of total thyroxine(TT4), free triiodothyronine(FT3) and free thyroxine(FT4) were lower than controls, and immediately after the release of arterial clamps, there was an upsurge of total triiodothyronine (TT3), TT4, FT3 and FT4 due to administered and/or endogeneously secreted catecholamines. The levels of the 7th day were comparable to the presurgical levels. The changes observed in donors and recipients were similar indicating that the hormonal changes observed are mostly due to surgical stress. Recovery in the hormonal status did not start in the first week of posttransplant period.     

Glycosylated proteins and serum lipid profile in complicated and uncomplicated NIDDM patients

In the present study, 58 diabetic patients (type II) comprising uncomplicated (27) and complicated (31) cases along with 38 healthy matched controls were investigated for glycosylated hemoglobin (HbA₁), glycosylated serum proteins (GSP) and serum lipid profile viz. triacylglycerol, total cholesterol, HDL-cholesterol (HDL-C), VLDL-C, LDL-C and their ratios. HbA₁ and GSP were significantly elevated in diabetic group as a whole when compared with controls (p<0.01), but comparison of mean values of complicated and uncomplicated group revealed (though higher in complicated) that the difference between two groups was not statistically significant (p>0.05). Follow-up studies showed that while GSP levels reflect variations in blood glucose over a shorter period of 15 days, those of HbA₁ do so for about 3 months. HbA₁ correlated with fasting blood glucose (p<0.01), whereas GSP showed correlation with both fasting (p<0.01) and postprandial (p<0.05) blood glucose. Hypercholesterolemia and hypertriacylglycerolemia were observed (p<0.01) in both the groups. However no significant change was seen in HDL-C (p>0.05) even after accounting for sex in both the groups. Interestingly TC:HDL-C was elevated significantly (p<0.01) in the above groups. These findings seem to suggest that at the levels of hyperglycemia, hypercholesterolemia and hypertriacylglycerolemia observed, some patients are prone to develop complications earlier.     

Biochemical markers of liver and kidney function are influenced by thyroid function-a case-controlled follow up study in Indian hypothyroid subjects

Thyroid hormones regulate the renal hemodynamics and basal metabolic rate of most cells. This hospital-based case-control study was done to evaluate the changes in biochemical markers of liver and kidney function in hypothyroid subjects before and after treatment. The study included 176 subjects randomly selected from Thyroid clinics. Serum T₃, T₄, TSH, Liver and Kidney Function tests were analysed using standard kits. Forty-six hypothyroid patients were re-evaluated 6 weeks after thyroxine substitution therapy. Hypothyroid subjects (n=80) showed significantly raised serum creatinine and uric acid levels as compared to euthyroid subjects (n=96). After 6 weeks of thyroxine replacement, serum creatinine and uric acid decreased significantly and were comparable to euthyroid group. A positive correlation of ALT, AST, uric acid, protein and albumin with TSH levels (p<0.05) and negative correlation of serum T₄ levels with ALT, AST, proteins (p<0.05) was observed in the hypothyroid group. Hypothyroidism results in reversible impairment of hepatorenal function.     

Effect of radiotherapy on serum sialic acid level in carcinoma cervix

Serum sialic acid levels were determined in 66 patients of carcinoma cervix and 25 control women matched for age. Mean sialic acid level was significantly elevated (p<0.001) in cancer cervix patients as compared to controls. Patients were treated with 50–65 Gy of radiation in 5–6.5 weeks. Post-therapy levels were again determined. Radiotherapy caused decline in serum sialic acid level in all the patients except one. Mean post-therapy level was significantly lower as compared to pretreatment level (p<0.001). It was also observed that fall in sialic acid level was significantly higher (p<0.05) in early stage patients as compared to late stage. No relationship was observed in the dose of radiation and fall in serum sialic acid level. A significantly higher fall in serum sialic acid level was observed in patients having complete clinical response as compared to partial or nonresponders to radiation treatment (p<0.001).     

Lipid Parameters, Doses and Blood Levels of Calcineurin Inhibitors in Renal Transplant Patients

The calcineurin inhibitors (CNIs) [cyclosporin A (CsA) and tacrolimus (Tac)] are currently the most widely prescribed drugs for maintenance of immunosuppression after renal transplantation. These immunosuppressants are associated with side effects such as hyperlipidemia. We evaluated the differential effects of different CNIs on serum lipid parameters in renal transplant patients. Moreover, the aim of this study is to investigate the relationships between doses and blood levels of CNIs, and blood levels of CNIs and lipid parameters retrospectively. Two groups of 98 non-diabetic renal transplant patients, each treated with different CNIs, were studied: group A (n = 50, mean age: 31 ± 10 years), CsA, mycophenolate mofetil/azathioprin, steroid; group B (I = 48, mean age: 34 ± 12 years), Tac, mycophenolate mofetil/azathioprin, steroid. In renal transplant patients, CNIs blood levels and doses were examined at 1, 3, 6, 9, and 12 months after transplantation. Biochemical laboratory parameters including plasma lipids [total-cholesterol (CHOL), low-density lipoprotein (LDL)–CHOL, high-density lipoprotein (HDL)–CHOL, and triglycerides (TG)], CNI levels and doses were examined at 1, 3, 6, 9, and 12 months after transplantation. None of the patients received anti-lipidemic drugs during the study period. Blood levels of CNIs were detectable in all whole-blood samples by Cloned- Enzyme-Donor Immunoassay (CEDIA). The relationship between CNIs blood levels and CHOL, (LDL)–CHOL, HDL–CHOL, TG were evaluated. The mean serum CHOL levels and LDL–CHOL levels of patients in group A were found significantly higher than the patients in group B during the 12 month of follow up (p < 0.05). There was no significant difference in TG and HDL–CHOL plasma levels between group A and group B (p > 0.005). In group A the daily dose of CsA was significantly correlated with the mean blood levels of CsA at the 1st and 3rd months (r = 0.387, p = 0.005; r = 0.386, p = 0.006), respectively. In group A, the daily dose of CsA was significantly correlated with the mean serum TG levels during the 12 month of follow up (r = 0.420, p = 0.003). In group B, the daily dose of Tac was significantly correlated with the mean blood level of Tac (r = 0.335, p = 0.020) at the 1st month. No correlation was found between mean Tac blood levels and lipid parameters during the 12-month of follow up (p > 0.05). Significant positive correlation was observed between the CsA blood levels and LDL–CHOL levels (r = 0.338, p = 0.027) at the 3rd month. In the renal transplant patients with well functioning grafts, CsA therapy is associated with increased CHOL and LDL–CHOL ratio which represents an increased atherogenic risk tended to be associated with CsA. Serum LDL–CHOL levels may be effected by blood CsA levels.     

Effect of supplementation of vitamin C and E on oxidative stress in osteoporosis

Osteoporosis encompasses a wide spectrum of conditions associated with imbalance of osteoclastic and osteoblastic activities. The increased activity of osteoclasts leads to increased free radical formation and hence lipid peroxidation. Present study probes into the role of antioxidants as a palliative treatment for osteoporosis. It involved 50 healthy controls and 75 clinically diagnosed osteoporosis patients. Both the groups underwent baseline assessment of biochemical markers viz. osteoblastic markers: serum Alkaline phosphatase. Free or ionic calcium and Inorganic phosphorus, osteoclastic markers: serum Tartarate resistant acid phosphatase and Malondialdehyde and the antioxidant status: serum Superoxide dismutase and Erythrocyte reduced glutathione. The osteoporotic group was then divided into groups A (Vitamin E-Evinal 400 mg), B (Vitamin C-Celin 500 mg), C (Vitamin E+C-Evinal+Celin) for antioxidant supplementation for a period of 90 days. The results reveal that there is significant fall in concentration of serum MDA (p<0.001), TrACP (p<0.01). Improvement in antioxidant status is reflected by significant rise in concentration of serum SOD (p<0.001) and erythrocyte GSH (p<0.001) after 90 days of antioxidant supplementation in osteoporosis. The findings indicate that on the whole bone status improved with prolonged antioxidant vitamin supplementation, which can be used as a palliative treatment for osteoporosis. The efficacy is not affected whether the vitamins are administered singly or conjointly.     

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.     

A preliminary report on the role of yoga asanas on oxidative stress in non-insulin dependent diabetes mellitus

Nineteen subjects of non-insulin dependent diabetes mellitus (NIDDM) between the age group of 30–60 yrs were studied to see the effect of specific yoga asanas on fasting and postprandial blood glucose (FBG, PPG), serum malondialdehyde (MDA) and glycosylated hemoglobin (HbA₁) in addition to drug treatment and diet control. The duration of diabetes ranged from 1–10 years. Patients with renal, cardiac and proliferative retinal diseases were excluded from the study. The same patients served as their own control. Subjects were called in the morning to the cardio-respiratory laboratory and were given training by a yoga expert. Yoga asanas included Suryanamskar, Tadasan, TriKonasan, Padmasan, Pranayam, Paschimottanasan, Ardhmatsyendrasan, Pavanmukthasan, Sarpasan and Shavasan. The asanas were done every day for 40 days for 30–40 min. FBG, PPG, serum MDA and HbA₁ were estimated before and after 40 days of yoga asanas regimen. Significant reduction was seen in FBG from 220 mg/dl to 162 mg/dl, PPG from 311 mg/dl to 255 mg/dl, MDA from 6 nmol/l to 3 nmol/l and HbA₁, from 8.8% to 6.4%. Subjects felt better and were relieved of their stresses and had an improvement in their day to day performance. The decrease was statistically significant (p<0.0001 for FBG and PPG, p<0.001 for MDA and for HbA₁).     

Serum gamma glutamyl transferase (γ-GT) activity in alcoholics with liver abscess and chronic alcoholics

Gamma Glutamyl Transferase (γ-GT) is a microsomal enzyme. Its activity in serum is assayed in alcoholics with liver abscess and alcoholics without liver abscess after screening by ultrasonography. The enzyme activity in serum is increased by 334% in the patients with liver abscess compared to normal control subjects (p<0.0001), and 172% when compared to patients with chronic alcoholism without liver abscess (p<0.0001). The enzyme activity was increased by 59.3% in the serum of patients without liver abscess compared to the normal control subjects (p<0.001). Measurement of γ-GT in serum appears to be a sensitive index in the diagnosis of alcoholics with liver abscess.     

Evaluating role of oxidative stress in determining the pathogenesis of falciparum malaria induced acute renal failure

Serum malondialdehyde was measured in sixty-one falciparum malaria cases, which include thirty uncomplicated, and thirty-one complicated with acute renal failure. Twenty-six healthy individuals were also studied as controls. Serum malondialdehyde level was found to be significantly elevated in falciparum malaria induced acute renal failure cases when compared with uncomplicated falciparum malaria (p<0.001) and healthy controls (p<0.001). A positive correlation with the raised urea, creatinine and bilirubin levels were significant (r=0.62, p<0.025; r=0.65, p<0.05 and r=0.72, p<0.001 respectively) indicating the severity of complication with rise of lipid peroxides in falciparum malaria induced acute renal failure cases.     

Paraoxonase activity and antibodies to oxidized-LDL in chronic renal failure patients on renal replacement therapy

Serum paraoxonase (PON1) and antibodies to oxidized-LDL (anti ox-LDL) were measured in chronic renal failure subjects on renal replacement therapy such as hemodialysis (HD) peritoneal dialysis (PD) and transplantation (Txp). Paraoxonase activity was significantly lower in HD and PD group (P<0.001) than in control subjects. In transplant patients, paraoxonase activity was not significantly different from that of controls. Antibodies to ox-LDL was significantly higher in HD, PD and Transplant patients (P<0.0001) compared to control subjects. High titers of antibodies were observed in the HD group compared to the PD and Transplant subjects. A decrease in paraoxonase activity and high titers of Antibodies to ox-LDL in the dialysis group suggest a decreased cardio protective effect of HDL and enhanced risk of premature cardiovascular complications. Whereas in case of transplant subjects, there seems to be restoration of PON1 activity, but elevated levels of anti-oxLDL could still be a potential atherogenic factor. Hence, we propose that estimation of these two parameters can be used as a useful index to measure the cardiac risk in the above patient category     

Lipid abnormalities in chronic renal failure

Lipid abnormalities remain to be a major cause of early mortality in patients with chronic renal failure (CRF). In present study, 114 (one hundred fourteen) CRF patients without any additional cause of dyslipidemia were divided into groups on the basis of etiologies of CRF. Blood samples from each group were analyzed for total cholesterol, triglyceride and HDL cholesterol along with blood urea nitrogen and serum creatinine. 25 healthy individuals without any obvious disease were taken as control. Patients from all the groups showed a marked hypertriglyceridemia of 232 (SD±77) mg/dl (P<0.001) as compared to control. Levels of HDL cholesterol were found to be significantly low 20 (±11) mg/dl (p<0.001) in all the groups. LDL cholesterol showed an increase 104 (±30) mg/dl as compared to control group which is not statistically significant. Present study reveals that, CRF patients show an uniform dyslipidemia irrespective of etiologies leading to CRF. This dyslipidemia is also independent of serum creatinine levels. Although, these lipid abnormalities may not solely cause mortality in CRF patients, they may act as modulators in accelerating atherogenesis which in turn cause early mortality in CRF patients.     

Design of Allele Specific PCR for Rapid Detection of CYP3A5 (A6986G) and Mdr-1 (C3435T) Polymorphisms

Single nucleotide polymorphisms in CYP3A5 (A6986G) and MDR-1 (C3435T) genes have been shown to be associated with the pharmacokinetics of tacrolimus in case of renal transplant recipients. Knowing these genotypes of the recipients before undergoing transplantation, is therefore essential for physicians to adjust the starting dose of tacrolimus in order to avoid drug induced nephrotoxicity. We have designed an allele specific PCR method for easier and rapid detection of these polymorphisms. 20 Indian renal transplant recipients on tacrolimus who developed nephrotoxicity within 1 month of transplantation and 58 Indian non-transplant subjects having the risk factors for kidney disease i.e. hypertension or diabetes or the family history of these, have been studied for these SNPs by allele specific PCR method. The data suggest that the heterozygosity of CYP3A5 and mutant allele frequency of MDR-1 SNP is higher in transplant patients as well as in general population.     

Effect of short term supplementation of tomatoes on antioxidant enzymes and lipid peroxidation in type-II diabetes

The objective of the present study is to evaluate the beneficial effect of tomatoes, which are rich source of Lycopene, relatively a new carotenoid known to play an important role in human health and disease. In this study lipid peroxidation rate was measured by estimating Malondialdehyde and the levels of serum enzymes involved in antioxidant activities like Super Oxide Dismutase, Glutathione Peroxidase, Glutathione Reductase, Reduced Glutathione, in type-II diabetic group (n=40) and age matched control group (n=50), and observed significantly lower levels of antioxidant enzymes and very high lipid peroxidation rate in type-II diabetes when compared to control group (p<0.001). Short term supplementation with tomatoes (cooked) to diabetic group for a period of 30 days, showed a significant improvement in antioxidant enzyme levels (p<0.001) and decreased lipid peroxidation rate (p<0.001) suggesting the supplementation with tomato lycopene may serve as the best method of preventing the oxidative stress in diabetic patients.     

Enzymuria pattern in early post renal transplant period: Diagnostic usefulness in graft dysfunction

Serum creatinine does not distinguish between various causes of graft dysfunction. Serial assay of proximal tubular enzymes N-Acetyl-D-glucosaminidase (NAG), Alanine aminopeptidase (AAP) and Gamma glutamyl transferase (GGT) in urine was done to assess their usefulness in distinguishing various causes of graft dysfunction. Daily serum creatinine and enzymuria were measured in 32 consecutive renal allograft recipients for first 15 postoperative days. Graft dysfunction was defined as >20% increase in serum creatinine and >100% increase in enzymuria over the baseline. The diagnosis of graft dysfunction was based upon clinical criteria, ultrasonography, cyclosporin trough level, allograft biopsy, response to anti-rejection therapy and alteration of cyclosporin dosage. Fifteen episodes of graft dysfunction were identified in 15 patients. The sensitivity and specificity of the enzymes (NAG, AAP and GGT) for predicting graft dysfunction were 87.5%, 86.9%, 88.5% and 98.2%, 98.2%, 97.9% respectively. There was a significant increase in enzymuria during acute tubular necrosis (ATN) and acute rejection episode compared to cyclosporin nephrotoxicity (p<0.01). Enzymuria assay provides a simple, reliable and noninvasive method to distinguish cyclosporin nephrotoxicity from acute tubular necrosis and acute rejection in renal allograft recipients.     

Can serum Glutathione-S-transferase levels in carcinoma cervix be a predictor of radiation response?

We conducted a pilot study wherein serum Glutathione-S-transferase levels were measured before and after radiotherapy in carcinoma cervix patients and correlated with response to treatment during a two-year follow-up period. Out of 17 patients who received radiotherapy, 9 showed a significant decrease (p<0.005) while 8 showed significant increase (p<0.004) in post radiotherapy glutathione-S-transferase values as compared to pre treatment values respectively. These patients were followed up for two years and we observed that 71% who had significant increase in post radiotherapy values had relapse of cancer within 2 years where as 66% of those who had significant decrease in post radiotherapy values had no evidence of relapse. This shows that alterations in serum Glutathione-S-transferase levels may help us to predict radiation response     

hs-CRP and oxidative stress in young CAD patients: A pilot study

Premature coronary artery disease (CAD) is common in India. We, therefore, studied oxidative stress, dyslipidemia, and high sensitivity-C reactive protein (hs-CRP) levels in young CAD patients. Present study consisted of male CAD patients below 40 years and age and sex matched healthy controls (n=30 each). Fasting blood samples were analyzed for serum lipid profile, malondialdehyde, antioxidant enzymes and hs-CRP levels. Dyslipidemia was observed in 90% of the young CAD patients, of which 72.2% showed increased serum triglycerides and decreased HDL-cholesterol. LDL-cholesterol levels were high in 77.8%. Serum malondialdehyde and hs-CRP levels were increased significantly (p<0.0001) as compared to controls. hs-CRP levels were in high risk range in all the young patients. However, glutathione peroxidase activity was reduced significantly (p<0.05). Our data suggests that elevated hs-CRP levels along with dyslipidemia and oxidative stress adds to the predictive value of premature CAD in young Indians.     

Unusually difficult clinical presentation of an infant suffering from congenital cytomegalovirus (CMV) infection combined with alpha 1-antitrypsin (A1AT) deficiency

Congenital Cytomegalovirus (CMV) infection and alpha 1-antitrypsin (A1AT) deficiency are separately well described entities, but their simultaneous occurrence can pose a special challenge to a clinician, especially dealing with optimal diagnostic as well as therapeutic approach. Congenital CMV infection is the most common vertically transmitted infection in developed countries. In 85–95% of newborns it runs asymptomatic, while in others it is presented with jaundice, petechias, hepatosplenomegaly and central nervous system damage. A1AT deficiency is on the other hand, the most common genetic liver disease in children, and the clinical spectrum varies from the accidentally detected increased levels of transaminases through to the severe infant cholestasis that can progress to cirrhosis. The following case report describes a two-month old male with severe clinical presentation of congenital CMV infection probably exacerbated due to A1AT deficiency comorbidity. The clinical manifestations and unusually difficult clinical signs this infant presented lead to assumption that the additional liver damage exists. Extensive laboratory analyses were performed, including PCR for CMV DNA, A1AT serum concentration, A1AT genotyping, followed and confirmed with phenotyping. Patient was treated parenteral with ganciclovir, what continued with oral valganciclovir and supportive therapy. Intensive and thorough supportive treatment of the infant resulted in satisfactory progress and excellent outcome. Patient was followed-up till the age of 18 months. The presented case provides excellent example about successful overcoming obstacles in differential diagnosis of A1AT in neonates and infants. Medical charts analysis was the methodology used in making this report.