ICMR-DBT Guidelines for Evaluation of Probiotics in Food.

There has been an increased influx of probiotic products in the Indian market during the last decade. However, there has been no systematic approach for evaluation of probiotics in food to ensure their safety and efficacy. An initiative was, therefore, taken by the Indian Council of Medical Research (ICMR) along with the Department of Biotechnology (DBT) to formulate guidelines for regulation of probiotic products in the country. These guidelines define a set of parameters required for a product/strain to be termed as ‘probiotic’. These include identification of the strain, in vitro screening for probiotic characteristics, animal studies to establish safety and in vivo animal and human studies to establish efficacy. The guidelines also include requirements for labeling of the probiotic products with strain specification, viable numbers at the end of shelf life, storage conditions, etc., which would be helpful to the consumers to safeguard their own interest.

Lipoprotein (a) phenotypes in south Indian patients with coronary artery disease.

BACKGROUND: Plasma lipoprotein (a) levels in the Indian population are varied; this study was undertaken to determine the relationship between plasma lipoprotein (a) levels and their phenotypes in a group of south Indian patients with coronary artery disease. METHODS AND RESULTS: A total of 104 patients with angiographically proven coronary artery disease were compared with 104 age- and sex-matched controls with no risk factors such as hypertension, diabetes and smoking. Lipoprotein (a) levels were measured by an in-house ELISA method and its phenotyping was done by SDS agarose gel electrophoresis. Plasma lipoprotein (a) levels were significantly elevated in patients with coronary artery disease as compared to controls (33.4+/-26.1 mg/dl v. 21.4+/-12.8 mg/dl; p<0.01). Lipoprotein (a) phenotyping showed that low-molecular weight isoforms were found only in 19.2% of the patients with coronary artery disease and their plasma lipoprotein (a) levels were significantly elevated compared to coronary artery disease patients with higher molecular weight isoforms (50.9+/-34.2 mg/dl v. 29.24+/-20.06 mg/dl; p<0.001). CONCLUSIONS: Plasma lipoprotein (a) levels are significantly elevated in patients with coronary artery disease as compared to controls. The commoner phenotype in a South Indian population is the larger apolipoprotein (a). in which the lipoprotein (a) levels are lower. Hence the contribution of lipoprotein (a) phenotype to the lipoprotein (a) levels in our population, if any, is modest.

Randomized controlled trial of once vs. twice daily gentamicin therapy in newborn.

OBJECTIVE: To compare the efficacy of once daily gentamicin administration to the conventional twice daily dosage schedule by estimation of serum gentamicin concentrations (SGC) in neonates. DESIGN: Randomized controlled trial. SETTING: Medical college hospital. SUBJECTS: Seventy three neonates of gestational age>32 weeks at risk or with clinical features of sepsis. METHODS: The subjects were divided into preterm and term groups. Babies in each of these groups were randomized to receive a single daily dose (4 mg/kg) or a twice daily dose (2.5 mg/kg) of injection gentamicin intravenously. Trough and peak SGC were estimated half an hour prior and one hour after the second dose. Statistical analysis was done using the equivalence method. RESULTS: In preterm as well as term babies, the mean peak and trough gentamicin levels were comparable in the two regimens. There is statistically significant evidence to show that the effect of once daily and twice daily dosage is similar. CONCLUSION: Once daily gentamicin administration is as effective as twice daily therapy and would be more cost effective.

Effect of aspirin and sodium salicylate on cataract development in diabetic rats.

The role of acetylation in the antiglycating and anticataract effects of aspirin (ASA) is explored by comparing ASA's effects with that of sodium salicylate (SS), a nonacetyl analog of ASA, on cataract development in diabetic rats. Streptozocin diabetic rats were provided with either ASA or SS, orally, for 24 weeks. Appropriate drug controls, normal controls and diabetic controls were run in parallel. Periodic estimations of blood glucose, glycated hemoglobin and assessments of cataract progression were done. After 24 weeks lenses were removed, homogenised and separated into water soluble fraction and urea soluble fraction. The glycated lens proteins in each fraction was quantified. Results were analysed statistically and interpreted in relation to serum salicylate levels. Both ASA and SS did not influence blood glucose levels. In the untreated diabetic groups the onset and progression of cataract was quicker and complete within 16 weeks. Both ASA and SS delayed the onset and progression in diabetic rats, but ASA's effect was more pronounced than that of SS. The levels of glycated Hb and lens proteins in diabetic rats were significantly reduced by ASA and not by SS for the same serum salicylate levels. ASA's anticataract potential far exceeds that of SS and it is ASA, and not SS, that inhibits protein glycation. Thus the results favour the hypothesis that acetylation plays a major role in ASA's anticataract effect via inhibition of glycation.

Maternal zinc indices and small babies.

BACKGROUND: Maternal zinc deficiency has been reported to be associated with foetal growth retardation. This study aimed to determine if zinc deficiency is associated with foetal growth retardation in south Indian women. METHODS: A prospective study was undertaken to evaluate the maternal zinc indices in those bearing small-for-gestational age babies and in those with appropriate-for-gestational age babies. Zinc levels in plasma, red blood cells and white blood cells in both groups were assayed in 65 patients with small-for-gestational age babies (regardless of cause) and 51 women with appropriate-for-gestational age babies. RESULTS: There was no significant difference in the mean (SD) plasma [67.5 (9) v. 70.67 (13.9)], red blood cell [47.26 (5.8) v. 45.69 (8.2)] and white blood cell [55.61 (10.5) v. 54.77 (12.4)] zinc levels in mothers who gave birth to small-for-gestational age babies and those who delivered appropriate-for-gestational age babies. The presence of predisposing factors for intrauterine growth retardation also did not influence the maternal zinc levels. CONCLUSION: Maternal zinc levels were not associated with intrauterine growth retardation in our population.

Comparison of HPLC & EMIT methods of cyclosporine assay in blood after bone marrow transplantation.

Cyclosporine (CsA) analysis in blood from patients who had undergone bone marrow transplantation for various haematological disorders was done both by high performance liquid chromatography (HPLC) and enzyme multiplied immunoassay technique (EMIT) and the results were compared. HPLC kit from Biorad Laboratories, USA, and EMIT kit from SYVA, UK, were used. The procedure for EMIT was slightly modified in-house to suit the Hitachi 704 discrete selective analyser. The CsA values obtained by these two methods correlated well within the therapeutic range (r value 0.96), HPLC method being most suitable outside the therapeutic range. Although HPLC is the ideal method for CsA, EMIT is quite suitable and can be adopted by any laboratory with an autoanalyser incorporating our modified procedure.

alpha 1-Antitrypsin deficiency in Indian patients with chronic obstructive airways and other pulmonary diseases.

OBJECTIVE: To determine alpha 1-antitrypsin (A1AT) deficiency in patients with chronic obstructive airways disease (COAD) and other pulmonary diseases. DESIGN: Observation study. SUBJECTS: 45 patients with COAD, 20 with bronchiectasis, 11 with pulmonary tuberculosis, 25 with chest malignancies and 42 healthy subjects. SETTING: Christian Medical College Hospital, Vellore, India. MAIN OUTCOME MEASURE: Serum A1AT level of 10% or less of the mean serum value of the control group was recognised as severe deficiency and A1AT level between 10 and 60% was considered as intermediate deficiency. RESULTS: 26 patients (18 with COAD, 2 with bronchiectasis, 3 with tuberculosis and 3 with chest malignancies) had intermediate A1AT deficiency. CONCLUSION: The finding of an A1AT deficiency in over a quarter of the patients comprising various categories of pulmonary diseases emphasises the need to explore the possibility of an underlying acquired cause existing either alone or in association with genetic defect in patients showing such a deficiency.

Detection & elimination of preanalytical errors in the determination of zinc in biological samples.

Exogenous contamination poses a major problem to accurate determination of trace metals in biological samples. Analysis of these elements in biological material entails adoption of special precautionary measures. In this study we have assessed the various procedural steps of sampling and analysis of zinc in order to identify and minimize extraneous contamination in the laboratory. In addition we have established reference limits (2 SD) for zinc in human plasma, erythrocytes and hair.

Adrenal function & the pattern of glucocorticoid induced eosinopenia in tropical pulmonary eosinophilia.

Plasma cortisol levels were estimated in 16 patients with tropical pulmonary eosinophilia (TPE; group A) by radioimmunoassay using 125I labelled cortisol. The cortisol levels showed diurnal variation, the mean levels were 10.22 +/- 4.5 micrograms/dl for the morning samples and 4.91 +/- 2 micrograms/dl for the night samples respectively and were within normal limits. Another six patients with TPE included in the study (group B) had an initial mean plasma cortisol level of 5.83 +/- 1.33 micrograms/dl. Half an hour after intramuscular administration of 250 micrograms of Synacthen (a synthetic glucocorticoid with corticotrophic activity), the mean cortisol level showed a significant rise up to 14.7 +/- 3.54 micrograms/dl (P < 0.01) thus indicating normal adrenocorticohypophysial functions in TPE. There was no significant alteration of total blood eosinophil counts before and after intramuscular Synacthen. An additional 6 patients with TPE (group C) who were given oral prednisolone 30 mg a day for 5 days which was subsequently tapered off in the next 5 days showed a spectacular mid-treatment fall in blood eosinophil levels with a post-treatment rise. In another 3 patients with TPE (group D) total blood eosinophil counts were estimated 4 h after intramuscular hydrocortisone and a prompt eosinopenic response was observed. This indicated that a dose related response to steroids in TPE is unlikely. The absence of eosinopenic response after Synacthen could have been due to the short (half an hour) interval when the eosinophil counts were repeated.

Primary hyperaldosteronism--diagnostic approach and management.

Primary hyperaldosteronism was detected in 1% of patients evaluated for secondary hypertension in a referral hospital in Southern India. The presence of hypokalemia with inappropriate kaliuresis (24 hr. urine K > 20mEq) was an important diagnostic clue. High resolution CT scans were found to be useful for localising the tumour. Preoperatively nifedipine and spironolactone were employed to correct hypertension and hypokalemia. The same drugs were also found to be excellent for long-term control of hypertension and hypokalemia in patients who had bilateral adrenal hyperplasia and aldosteronism.

Comparison of cardiovascular risk factors in type II (non-insulin dependent) diabetics with and without coronary heart disease.

Cardiovascular risk factors in NIDDM were studied by comparing 175 subjects with coronary heart disease (CHD) to 173 subjects without CHD; both groups were matched with regard to male to female ratio, age at diagnosis of diabetes and body mass index. The risk factors included were hypertension, poor metabolic control, smoking and lipid abnormalities. Since the mean known duration of diabetes in subjects with CHD was longer compared to those without CHD (12.93 +/- 7.23 and 6.25 +/- 5.66) and sub sample of subjects from both groups with duration of diabetes with 15 years or less were also analysed for comparison. Even after adjustment of duration the clustering of vascular complication in the subjects with CHD was striking. Presence of low HDL cholesterol was significant in both men and women diabetics with CHD (p < 0.01); while hypertension and poor metabolic control showed a strong positive correlation to CHD in women (p < 0.01 & p < 0.05). Multiple logistic analysis carried out separately in men and women showed that both low HDL cholesterol and elevated serum triglycerides showed strong association to CHD in both sexes; while in women in addition hypertension and insulin therapy also had a positive correlation to CHD (p < 0.01). Furthermore the influence of known duration of diabetes was not observed to be a significant contributor to the cardiovascular risk factors, since the above mentioned risk factors remained statistically significant in the subsample of patients with duration of diabetes less than 15 years.

Prevalence & pathogenesis of hypophosphatemia in ventilated patients.

Hypophosphatemia was found in 12 (43%) patients within 24-36 h of mechanical ventilation in a group of 28 patients in an intensive care unit. The hypophosphatemic patients had a significant lowering of renal phosphorus threshold (P = 0.005) and inappropriate phosphaturia. These abnormalities resolved once ventilation was discontinued. Serum parathyroid hormone (PTH) levels were unaltered in this group of patients suggesting that some factor other than PTH was responsible for hypophosphatemia. This study has demonstrated that abnormalities of renal phosphate handling can cause hypophosphatemia in ventilated patients.

Prevalence of diabetic nephropathy in non-insulin dependent diabetics.

Renal involvement was studied in 538 consecutive NIDDM subjects (271 males and 267 females). The mean (SD) age of males was 55.4 (11.0) and of females 51.0 (10.5). Diabetic nephropathy was present in 8.9 per cent of the patients (urinary albumin excretion greater than 200 micrograms/min) and another 19.7 per cent had microalbuminuria (20-200 micrograms/min). Male predominance was striking in the macroalbuminuric group (P less than 0.001). The age of the patients and duration of diabetes in patients with micro and macroalbuminuria were significantly higher as compared to those in normoalbuminuric group (P less than 0.001). Patients with micro and macroalbuminuria had significantly elevated blood sugars and blood pressures (P less than 0.01). The prevalence of vascular complications were found to be higher in the macroalbuminuric group (P less than 0.01). Male sex, older age, longer duration of diabetes, poor glycaemic control and raised blood pressure were significant risk factors in the development of diabetic nephropathy.

Thyroid stimulating hormone receptor antibody in thyroid diseases.

Thyroid stimulating hormone receptor antibody (TRA) was estimated as a measure of TSH binding inhibitory immunoglobulin (TBII) in 48 persons. These included (i) 14 controls; (ii) 23 patients with Graves' disease who were tested for TRA within 3 months of commencing treatment with carbimazole of which 13 were studied serially; (iii) 5 patients with toxic nodular goitre; (iv) 4 with euthyroid exophthalmos; and (v) 2 neonates of thyrotoxic mothers. TRA was measured with an RIA system, while total thyroxine (T4), free thyroxine concentration (FTC) and TSH were also estimated along with TRA. All controls showed undetectable TRA levels; 87 per cent of patients with Graves' disease were TRA positive within 3 months of starting carbimazole therapy. In the serial study, 5 patients with Graves' disease who had undetectable TRA initially remained so while on treatment. Seven out of the remaining 8 patients showed a decline of TRA levels to normal over 3 to 18 months. This decline coincided with clinical and biochemical recovery.