Savita Verma Attri

Erythrocyte Metabolism and Antioxidant Status of Patients with Wilson Disease with Hemolytic Anemia

Wilson disease (WD) is an autosomal recessive disorder due to the defect in ATP7B gene characterized by excessive accumulation of copper in the liver with progressive hepatic damage and subsequent redistribution to various extrahepatic tissues including the brain, kidneys, and cornea. Strikingly, the total serum copper concentration is always low in WD, even though the non-ceruloplasmin copper level is still expected to be high. To assess the role of free radical reactions catalyzed by non-ceruloplasmin copper, we investigated erythrocyte metabolism and oxidative stress as a mechanism for hemolysis in eight WD patients during episodes of acute hemolysis and compared them with eight follow-up cases of WD on d-penicillamine therapy and eight healthy, age-matched children. Elevated levels of non-ceruloplasmin copper were found in all the WD patients during an episode of hemolytic anemia. There was marked inhibition in erythrocyte enzymes, namely, hexokinase, total adenosine triphosphatase (ATPase), and glucose-6-phosphate dehydrogenase (G-6-PD) from WD patients compared with patients on penicillamine and healthy children, indicating altered erythrocyte metabolism during a hemolytic crisis. Antioxidant status was also found to be compromised as is evident from decreased glutathione (GSH) levels, decreased antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), increased lipid peroxidation, and deranged plasma antioxidants. Uric acid showed maximum decrease followed by ascorbic acid. These findings suggest that the free radical production by elevated non-ceruloplasmin copper through transition metal catalyzed reactions leads to oxidative injury resulting in altered erythrocyte metabolism and severely compromised antioxidant status of WD patients during hemolytic anemia.

The deferiprone and deferasirox combination is efficacious in iron overloaded patients with β-thalassemia major: A prospective, single center, open-label study

The high cost, coupled with the need for continuous infusion, renders Desferrioxamine (DFO), a non‐feasible option for iron‐chelation in a large majority of patients with β‐thalassemia major in developing countries. Monotherapy with deferiprone (DFP) or deferasirox (DFX) may not always attain optimal control, particularly in heavily iron‐loaded patients. Combination of DFP and DFX is a potential alternative.

Vitamin D deficiency in critically ill children with sepsis.

Background: Data on the prevalence of vitamin D deficiency (VDD) in critically ill children with sepsis and its association with illness severity and outcome are limited. Aim: To investigate the prevalence of VDD in critically ill children with sepsis. Methods: One hundred and twenty-four critically ill children with sepsis aged 1–12 years were prospectively enrolled in a paediatric intensive care unit (PICU) in North India over a 1-year period. Demographic data, clinical signs and risk factors for VDD, Paediatric Index of Mortality III (PRISM III) score, and sequential organ failure assessment (SOFA) score were recorded. Plasma 25-hydroxy vitamin D [25(OH)D] levels were measured by ELISA within 24 hours of admission. The occurrence of septic shock, multiple organ dysfunction syndrome (MODS) and healthcare-associated infection (HCAI), need for mechanical ventilation and catecholamines, length of PICU stay and mortality were also recorded. Cases were compared with 338 apparently healthy children for baseline variables and vitamin D status. Results: Prevalence of VDD [25(OH)D level < 50 nmol/L] was higher among critically ill children with sepsis compared to healthy controls (50.8% vs 40.2%, P = 0.04). VDD was not associated with any significant difference in baseline demographic variables or risk factors for VDD. Although there was a trend toward increased PRISM III score, septic shock, MODS, HCAI, need for mechanical ventilation and catecholamines, length of PICU stay, and mortality, the difference was not statistically significant. Conclusion: A high prevalence of VDD in critically ill children with sepsis was found but it was not associated with greater severity of illness or other clinical outcomes.

Kinetic characterization of Zinc transport process and its inhibition by Cadmium in isolated rat renal basolateral membrane vesicles: In vitro and In vivo studies

We firstly characterized zinc uptake phenomenon across basolateral membrane vesicles (BLMVs) isolated from normal rat kidney. The process was found to be time, temperature, and substrate concentration dependent, and displayed saturability. Zn2+ uptake was competitively inhibited in the presence of 2 mM Cd with Ki of 3.9 mM. Zinc uptake was also inhibited in the presence of sulfhydryl reacting compound suggesting involvement of {–}SH groups in the transport process. Further, to elucidate the effect of in vivo Cd on zinc transport in BLMVs, Cd nephrotoxicity was induced by subcutaneous administration of CdCl2 at dose of 0.6 mg/kg/d for 5 days in a week for 12 weeks. An indolent renal failure developed in Cd exposed rats was accompanied with a significantly high urinary excretion of Cd2+, Zn2+ and proteins. The histopathology and electron microscopy of kidneys of Cd exposed rats documented changes of proximal tubular degeneration. Notably, Cd content in renal cortex of Cd exposed rats was 215 μg/g tissue that was higher than the critical concentration of Cd in kidneys which was associated with significantly higher Zn and metallothionein (MT) contents. Zinc uptake in BLMVs isolated from kidneys of Cd exposed rats was significantly reduced. Further, kinetic studies revealed that decrease in zinc uptake synchronized with decrease in maximal velocity (Vmax) and increase in affinity constant which is suggestive of decreased number of active zinc transporters. Furthermore, conformational modulation of Zn transporter in BLM was further supported by observed variation in transition temperature for zinc transport in BLMVs isolated from Cd-exposed kidney.

Nutritional status and complications in children with diabetic ketoacidosis.

Objective: Diabetic ketoacidosis in children continues to be an important cause of morbidity and mortality, especially in developing economies as a result of malnutrition, a high rate of infections, and delay in seeking timely medical care. Malnutrition also increases the risk of diabetic ketoacidosis-related complications. The objective of this study was to assess the nutritional status of patients presenting with diabetic ketoacidosis and correlate it with the incidence of complications at presentation and those encountered during the course of illness. Design: Prospective study. Setting: Pediatric emergency and intensive care units, Advanced Pediatrics Centre, PGIMER, Chandigarh, India. Patients: Thirty-three children between 1 month and 12 yrs of age presenting with diabetic ketoacidosis between July 2008 and June 2009 were enrolled consecutively and assessed for nutritional status by anthropometric parameters (body weight, crown–heel length/height, mid–upper arm circumference, triceps and subscapular skin fold thicknesses), biochemical parameters (serum albumin, zinc, magnesium, vitamin A levels), and preillness dietary history (by pretested Food Frequency Questionnaire). Patients were classified as malnourished or normally nourished based on the weight for age criteria matched for Indian standards. The incidence of complications (electrolyte imbalances, hypoglycemia, sepsis, cerebral edema, etc.) and outcome in terms of survival or death in both the groups were compared with Student’s t-test for parametric data, Mann-Whitney U test for nonparametric data, and chi-square test for categorical variables. Interventions: None. Measurements and Main Results: Anthropometric assessment showed that 11 of 33 (33.3%) were malnourished. Preillness dietary history revealed that 16 (48.5%) were calorie- and protein-deficient (known diabetic n = 7; new onset n = 9), whereas 11 (33.3%) were only calorie-deficient (known diabetic n = 2). Hypoalbuminemia was seen in 21 (63.6%), hypovitaminosis A in eight (24.2%), and low zinc levels in three (9%). The malnourished and normally nourished groups were similar with respect to demographics, precipitating factors, severity of diabetic ketoacidosis, treatment received, and outcome. However, the incidence and severity of therapy-related hypokalemia (100% vs. 72.7%; p = .05) and hypoglycemia (63.6 vs. 13.6%; p = .004) were significantly higher in the former as compared with the latter. The mean ± SD admission serum potassium levels were similar in both the groups (3.4 ± 0.8 mEq/L in the malnourished vs. 3.5 ± 0.7 mEq/L in the normally nourished) with the malnourished group showing a significant fall at 6 hrs after start the of diabetic ketoacidosis protocol (2.8 ± 0.8 mEq/L vs. 3.6 ± 0.7 mEq/L; p = .033), although the mean rate and dose of insulin infusion were similar. The fall in blood glucose (mean ± SD mg/dL) at 12, 24, and 36 hrs after onset of the diabetic ketoacidosis protocol was also significantly greater in the malnourished group as compared with the normally nourished diabetic ketoacidosis (195 ± 69.1 and 272.61 ± 96.3, p = .02; 171 ± 58.5 and 257 ± 96.3, p = .05; and 153.75 ± 49.6 and 241.71 ± 76.3, p = .04, respectively). The incidence of hypophosphatemia, hypomagnesemia, cerebral edema, renal failure, sepsis, and septic shock was similar in both the groups. There were two deaths, both resulting from complicating cerebral edema and renal failure and unrelated to the nutritional status of the patients. Conclusions: The incidence and severity of therapy-related hypokalemia and hypoglycemia were significantly higher in the malnourished as compared to the normally nourished diabetic ketoacidosis. Other diabetic ketoacidosis-related complications and outcome were similar in both the groups.

Risk factors for thromboembolism and pulmonary artery hypertension following splenectomy in children with hereditary spherocytosis.

The aim was to study risk‐factors for vascular thrombosis and incidence of pulmonary artery hypertension (PAH) in splenectomized children with hereditary spherocytosis (HS) at a single center.

Effect of 6-months' vitamin D supplementation on residual beta cell function in children with type 1 diabetes: a case control interventional study.

Abstract Background: The aim of this study was to evaluate the effect of short-term vitamin D supplementation on the decline of residual beta cell function (RBCF) in children with type 1 diabetes (T1D). Methods: The study involved an intervention group (cholecalciferol 2000 IU/day and calcium 25 mg/kg/day for 6 months) comprising 15 children aged 6–12 years and within 1–2 years of diagnosis of T1D. Fifteen age-matched T1D patients were followed up as controls. Stimulated C-peptide levels were estimated at baseline and 6 months. Results: The mean decrease in stimulated C-peptide levels in the intervention group was lower (–0.048±0.15 ng/mL) as compared with the controls (–0.107±0.23 ng/mL) but did not reach statistical significance (p=0.472). The percent decrease in stimulated C-peptide from baseline to endpoint (8.3% vs. 20.3%, p=0.357) and the monthly decrease (0.008 ng/mL vs. 0.017 ng/mL, p=0.22) were non-significantly lower in the intervention group compared with the control group. Three (20%) patients progressed to undetectable stimulated C-peptide (≤0.01 ng/mL) over the study period in the control group as compared with one (6%) in the intervention group (p-value 0.260). Conclusions: There was a trend towards lesser decline of RBCF with short term cholecalciferol supplementation in children with T1D. Further larger studies are urgently needed to explore the beneficial effects of the relatively inexpensive vitamin D supplementation on RBCF.

Relationship of High Sensitivity C-Reactive Protein Levels to Anthropometric and other Metabolic Parameters in Indian Children with Simple Overweight and Obesity.

CONTEXT High senstivity C-reactive protein (hsCRP) levels correlate well other parameters of obesity related metabolic syndrome (MS) and can be used as predictors of future cardiovascular disease risk. There is limited data on hsCRP levels in Indian children with simple obesity. AIM To study the relationship of hsCRP levels with various anthropometric as well as metabolic parameters in children with simple overweight and obesity. MATERIALS AND METHODS This case control study was conducted in Paediatric Endocrinology clinic of a tertiary care hospital in Northern India. Levels of hsCRP were estimated in 100 overweight and obese children (BMI between 85(th) and 95(th) percentiles according to age & gender specific CDC 2000 growth charts) aged between 6 and 16 years and in 100 nearly age and sex matched healthy controls. These levels were then correlated to various anthropometric (body mass index, BMI; waist circumference, WC; hip circumference, HC; waist hip ratio, WHR; blood pressure) and biochemical (fasting blood glucose, FBG; total cholesterol, TC; high-density lipoprotein-cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; very low-density lipoprotein-cholesterol, VLDL-C; triglycerides, TG) parameters. RESULTS Mean levels of hsCRP were significantly higher in the study group (3.92±2.20 versus 2.15±1.05 mg/L) as compared to controls. Significantly more (58% versus 10%) subjects in the study group had hsCRP (>3 mg/L). Of all the parameters studied, only BMI showed a positive correlation with hsCRP levels in the study group. Multiple logistic regression analysis for predicting outcome of high hsCRP showed positive correlation with BMI; with every 1 kg/m(2) increase in BMI, odds of high hsCRP level were increased by 37% (OR=1.37; 95% CI 1.23-1.53, p-value <0.0001). Mean values of all the biochemical parameters except HDL-C were significantly higher in the study group. CONCLUSION Levels of hsCRP were significantly elevated in overweight and obese children as compared to non-obese children. In addition, these patients also showed abnormalities of lipid and glucose metabolism.

Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial.

Aim:  To compare the incidence of hyponatremia in full‐term neonates with severe hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5% dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET).

Evaluation of micronutrient profile of North Indian children with cystic fibrosis: a case-control study

Background:Data on the micronutrient levels in children with cystic fibrosis (CF) are not available from developing countries, wherein the nutritional profile of children is quite different from that of Western countries.Methods:Levels of fat-soluble vitamins (A, D, and E) and trace metals (iron, copper, and zinc) were measured in 27 CF cases and 27 controls.Results:CF cases had significantly low levels of all studied micronutrients compared with controls, and the levels were even lower in cases with exacerbation than in stable CF cases. Prevalence of deficiency of vitamin D, vitamin E, iron, copper, and zinc was significantly higher in cases than in controls, whereas vitamin A deficiency was almost equal in both the groups.Conclusion:The prevalence of deficiency of vitamins A, D, and E and iron, copper, and zinc was high in CF cases, and their levels were significantly lower in cases than controls. CF cases should be regularly monitored for these micronutrients, and appropriate supplementation should be considered.