A cross-sectional study on thrombopoietin levels in immune thrombocytopenia and its correlation with platelet count, megakaryocytes, and treatment response.

INTRODUCTION: Thrombopoietin (TPO) being the major regulator of megakaryopoiesis is expected to show a compensatory increase in immune thrombocytopenia (ITP), however, it is not so observed. This study was undertaken to measure TPO levels in ITP and assesses its association with platelet count, megakaryocytes, and response to steroid therapy. MATERIALS AND METHODS: A total of 41 cases of ITP and twenty controls with normal platelet count were enrolled in this prospective study. Complete blood count, bone marrow examination, and ELISA for serum TPO were measured. Response to steroid therapy was evaluated for thirty cases. RESULTS: The TPO levels were increased in 80.5% of patients in comparison to the controls. The degree of rise, however, was variable. On analyzing low, normal, and high TPO levels with reference to platelet and megakaryocyte count no statistically significant difference was observed. Raised TPO levels were seen with significant lowering of functional megakaryocytes. The mean TPO levels in nonresponders were higher than responders but highly variable and statistically nonsignificant. CONCLUSION: Quantitative alterations in TPO are in a way regulated by qualitative efficacy of megakaryocytes rather than platelet or megakaryocyte count. Nonresponders with markedly increased TPO levels (due to qualitative megakaryocyte injury) are less likely to respond to TPO receptor agonist.

Model for Early Prediction of Preeclampsia: A Nested Case Controlled Study in Indian Women.

Purpose: Preeclampsia (PE) affects 5-7% of the pregnancies worldwide, and is one of the most dreaded disorders of pregnancy contributing to maternal and neonatal mortality. PE is mostly presented in the third trimester of pregnancy. Here, we used serum placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to develop a model for predicting PE in Indian women in early second trimester. Methods: In this case-control study, a total 1452 healthy pregnant women were recruited. Blood samples were collected at the following gestational weeks (GWs), 12-20 (GW1), 21-28 (GW2) and 29-term (GW3), and post-delivery. Body mass index (BMI) was calculated by anthropometric measurements. Serum sFlt-1, PIGF and VEGF were analyzed by ELISA. A predictive model for PE was developed using multivariable logistic regression analysis. Results: In PE cases, serum PlGF and VEGF levels were significantly lower at each GW, while serum sFlt-1 was lower only at GW1, relative to age-matched controls, (n = 132/group). Age-matched comparison between PE cases and controls indicated that sFlt-1 was associated with decreased PE outcome (Odds ratio. OR = 0.988, CI = 0.982-0.993), whereas sFlt-1/PlGF ratio (OR = 1.577, CI = 1.344-1.920) and BMI (OR = 1.334, CI = 1.187-1.520) were associated with increased PE outcome. Logistic regression was used to develop a predictive model for PE at GW1. Using testing dataset, model was externally validated which resulted in 88% accuracy in predicting PE cases at 0.5 probability cutoff. Conclusion: Prediction model using sFlt-1, sFlt-1/PlGF ratio and BMI may be useful to predict PE as early as 12-20 weeks in women with optimal sensitivity and specificity.

Association of IL-10 gene (-1082A>G, -819C>T and -592C>A) polymorphism and its serum level with metabolic syndrome of north Indian subjects.

Metabolic syndrome (MetS) is an inflammatory disorder, in which various cytokines play important role in tilting balance towards disease state. Interleukin-10 (IL-10) is an important antiinflammatory cytokine, but its genetic polymorphisms and serum levels in Indian MetS subjects are unknown. Three IL-10 gene polymorphisms (-1082A>G (rs1800896), -819C>T (rs1800872) and -592C>A (rs1800871)) were genotyped with PCR-RFLP in MetS subjects (n = 384) and age/sex matched control subjects (n = 386). Serum IL-10 was measured using enzyme-linked immunosorbent assay. Serum IL-10 level was significantly low in MetS subject and significantly correlated with clinicobiochemical parameters of MetS. Of three investigated promoter polymorphisms, IL-10 -819C> T and -592C>A were significantly associated with risk of MetS. The mutant alleles -819T and -592A of IL-10 gene polymorphism were significantly higher in MetS subjects compared to controls. Of the four different haplotypes obtained, common ACC haplotype and rare GTA haplotype of IL-10 polymorphisms were associated with MetS. The mean of fasting insulin and HOMA-IR were significantly different between the genotypes of both -819 C>T and -592C>A polymorphisms of IL-10 in MetS subjects. These results suggested that polymorphisms in IL-10 gene (-819C>T and -592C>A), haplotypes (ACC and GTA) and serum level are significantly associated with risk of MetS. IL- 10 -819C>T and -592C>A polymorphic variants are also significantly associated with insulin level and homeostasis model assessment-insulin resistance in north Indian MetS subjects.

Nutrition for diabetic retinopathy: plummeting the inevitable threat of diabetic vision loss.

Diabetic retinopathy (DR) is among the leading causes of preventable blindness. Hyperglycemia, hypertension, hyperlipidemia and anemia majorly predispose its pathogenesis. The current treatment modalities of DR include laser photocoagulation therapy, intravitreal corticosteroids, intravitreal anti-vascular endothelial growth factor (VEGF) agents and vitreo-retinal surgery which are costly, highly invasive, unproven for prolonged use and opted in advanced stages of DR. By then retina already encounters a vast damage. Nutrients by their natural physiological, biochemical and molecular action can preserve retinal structure and functions by interfering with the various pathological steps prompting DR incidence, thereby altering the risk of developing this ocular morbidity. Nutrients can also play a central role in DR patients resistant towards the conventional medical treatments. However due to the byzantine interplay existing between nutrients and DR, the worth of nutrition in curbing this vision-threatening ocular morbidity remains silent. This review highlights how nutrients can halt DR development. A nutritional therapy, if adopted in the initial stages, can provide superior-efficacy over the current treatment modalities and can be a complementary, inexpensive, readily available, anodyne option to the clinically unmet requirement for preventing DR. Assessment of nutritional status is presently considered relevant in various clinical conditions except DR. Body Mass Index (BMI) conferred inconclusive results in DR subjects. Subjective Global Assessment (SGA) of nutritional status has recently furnished relevant association with DR status. By integrating nutritional strategies, the risk of developing DR can be reduced substantially. This review summarizes the subsisting knowledge on nutrition, potentially beneficial for preventing DR and sustaining good vision among diabetic subjects.

Apolipoprotein A-I and B and Subjective Global Assessment relationship can reflect lipid defects in diabetic retinopathy.

OBJECTIVE: Elevated lipid levels increase complications of diabetic retinopathy (DR). Uncontrolled diabetes increases these complications and causes unintentional weight loss, indicating an apparently normal body mass index (BMI). Thus, it is easy to assume that patients with DR and a normal BMI have optimal lipid status. Apolipoprotein (Apo) A-I and Apo B levels differentially indicate serum lipid status in DR. Subjective Global Assessment (SGA) scores are associated with DR status. If SGA scores and serum Apo A-I and B levels are found to be interrelated, their relationship can reflect lipid defects in patients with DR despite apparently normal BMI. The aim of the present study was to investigate the possible relationship between serum Apo A-I and B levels and SGA scores of patients with DR. METHOD: This was a case-control study conducted from November 2011 to April 2014. Serum Apo A-I and B levels and SGA scores were calculated for 40 healthy controls, 48 individuals without DR, 49 nonproliferative DR cases, and 48 proliferative DR cases. Pearson's correlation analysis was applied between Apo A-I, Apo B, Apo B/Apo A-I ratio, and SGA scores. RESULTS: Negative correlation was observed between serum Apo A-I level (r = -0.567, P < 0.001) and positive correlation between serum Apo B level (r = 0.451, P < 0.001) and Apo B/Apo A-I ratio (r = 0.597, P < 0.001) with escalating SGA scores. CONCLUSION: To our knowledge, this is the first study to report a novel correlation between serum Apo A-I, Apo B and Apo B/Apo A-I ratio and SGA scores. SGA scores can help predict lipid abnormalities in patients with DR even when they have an apparently normal BMI.

Interrelationship of elevated serum Advanced Glycation End-product levels and malnutrition (Subjective Global Assessment) scores with the severity of retinopathy in type II diabetes.

BACKGROUND AND AIMS: Hyperglycemia in diabetes causes endogenous formation of Advanced Glycation End-products (AGEs) which accumulate in various body parts including retina causing diabetic retinopathy. AGEs also originate from exogenous dietary sources contributing to the body's AGE pool. Currently, curing of diabetic retinopathy is mainly focused on medication, surgical or laser interventions and not much emphasis is given on preventing or halting its occurrence or advancement to more severe stages, nutritionally. Planning a 'low glycemic index-low AGE' diet therapy for diabetic subjects can reduce endogenous and exogenous origin AGEs in the body and help in controlling retinopathy. Sound and accurate assessment of nutritional status is a crucial step for planning a therapeutic diet for this condition. As this aspect has not gained sufficient attention till now we are assessing the association of serum Advanced Glycation End-product (AGE) levels with the severity of diabetic retinopathy and for the first time estimating the nutritional status of subjects with this eye disorder for long term patient care. METHODS: This was a tertiary care centre-based, case-control study involving sixty three consecutive cases with diabetes divided as 21 cases with diabetes but no retinopathy, 21 cases with non proliferative diabetic retinopathy (NPDR), 21 cases with proliferative diabetic retinopathy (PDR) along with 21 healthy controls. Serum AGE levels of all the cases and controls were evaluated by Enzyme Linked Immuno Sorbent Assay (ELISA) and nutritional status was assessed by anthropometric measurements and SGA scores. RESULTS: Serum AGE levels were found significantly elevated in PDR group when compared with no retinopathy (p < 0.05) and control (p < 0.001) group. Control group was also significantly different from (p < 0.05) from NPDR group. Increase in SGA scores was statistically significant amongst the four study groups though other indices of nutritional status showed no definite trend with the increasing severity of retinopathy. CONCLUSION: Our study shows that serum AGE levels are potential risk markers of diabetic retinopathy and SGA can be used as a regular tool for the assessment of nutritional status of diabetic retinopathy subjects which will help planning a 'low glycemic index-low AGE' therapeutic diet for halting this morbidity.

Resistin 420C/G gene polymorphism on circulating resistin, metabolic risk factors and insulin resistance in adult women.

OBJECTIVE: To investigate the frequency association between resistin gene polymorphism with its circulating levels, metabolic risk factor and insulin resistance in adult women. DESIGN: Totally 615 subjects were enrolled for the study, 305 women were with metabolic syndrome and 310 women were without metabolic syndrome according to NCEP-ATP III criteria. Fasting circulatory level of resistin, insulin, plasma glucose and lipid profiles were estimated along with calculation of insulin resistance. Resistin 420C/G promoter region polymorphism was done by RFLP method. RESULTS: Variant genotype (CC vs CG+GG) (p<0.001: OR=2.22: 95% CI=1.60-3.10) of 420C/G resistin gene polymorphism was less frequently observed in control population. Further dividing subjects into two groups according to absence (Resistin -1) or presence (Resistin-2) of the G allele, significantly high levels of triglyceride (p<0.001), plasma glucose (p=0.012), systolic blood pressure (p<0.001), diastolic blood pressure (p<0.001), waist hip ratio (p<0.001), body mass index (p<0.001) and resistin (p<0.001), were observed in resistin-2 group. CONCLUSION: Present study shows that 420C/G polymorphism of resistin gene directly correlated to its high circulating level and metabolic risk factors, specifically markers of obesity and atherosclerosis, so it may have an important role in the development of metabolic syndrome and cardio metabolic diseases.

Calcitonin gene- and parathyroid hormone-related peptides in normotensive and preeclamptic pregnancies: a nested case-control study.

PURPOSE: To identify whether CGRP and PTHrP serve as screening biomarkers for early detection of preeclampsia or even before the development of preeclampsia in early pregnancy. METHODS: It was a nested case-control study. The subjects were divided into normotensive (controls) and preeclamptic (cases) groups. Serum samples of 132 cases and 132 controls were collected during pregnancy at three different gestational periods and one sample post delivery, from within the cohort of pregnant women reporting to antenatal clinic. Circulating levels of CGRP and PTHrP were analyzed by enzyme-linked immunosorbent assay. RESULTS: Maternal serum concentrations of CGRP and PTHrP increased with the advancement of gestation age in both normotensive and preeclamptic pregnancies but the significantly less increased levels were observed in preeclamptic pregnancies as compared with normotensive pregnancies. In postpartum period level of CGRP significantly falls in both groups although level of PTHrP continues to increase even after delivery. Maternal serum CGRP and PTHrP concentrations were positively correlated with the infant's birth weights. CONCLUSION: Maternal circulating CGRP and PTHrP concentrations were significantly lower in women with preeclampsia, which may contribute to the development of preeclampsia.

Impact of Yoga Nidra on menstrual abnormalities in females of reproductive age.

OBJECTIVES: The aim of this study was to observe the effect of Yoga Nidra practice on hormone levels in patients who had menstrual irregularities. DESIGN: The study was a randomized controlled trial. SETTINGS/LOCATION: The study was conducted in the Department of Obstetrics and Gynecology at Chhatrapati Sahuji Maharaj Medical University, Uttar Pradesh, Lucknow, India. SUBJECTS were divided randomly into 2 groups-an intervention and a control group, with 75 subjects in each group. Of these subjects, 126 completed the study protocol. SUBJECTS: This study involved 150 subjects with menstrual irregularities; 126 of whom completed the protocol. INTERVENTIONS: The intervention was the practice of Yoga Nidra. The yogic intervention duration was 35-40 minutes/day, five times/week for 6 months. An estimation of hormonal profile was done for both groups at baseline and after 6 months. RESULTS: Thyroid-stimulating hormone (p<0.002), follicle-stimulating hormone (p<0.02), luteinizing hormone (p<0.001), and prolactin (p<0.02) were decreased significantly in the intervention group, compared with the control group. CONCLUSIONS: The present study demonstrated the efficacy of Yoga Nidra on hormone profiles in patients with menstrual irregularities. Yoga Nidra practice was helpful in patients with hormone imbalances, such as dysmenorrhea, oligomenorrhea, menorrhagia, metrorrhagia, and hypomenorrhea.

Does microalbuminuria at mid-pregnancy predict development of subsequent pre-eclampsia?

AIM: The aim of this study was to evaluate microalbuminuria at mid-pregnancy, using the albumin-to-creatinine ratio (ACR), as a predictor of pre-eclampsia. MATERIAL AND METHODS: This prospective observational study was carried out on 144 normotensive women, aged<35 years, body mass index<25kg/m², and live singleton pregnancy between 24 and 28 weeks. In all, the ACR was measured in spot random urine samples. Normoalbuminuria was an ACR of <30 mg/g, whereas microalbuminuria was an ACR of 30-299 mg/g creatinine. All were followed till delivery. Primary outcome was the development of pre-eclampsia. The secondary outcome measures were preterm births and neonatal birthweight. Statistical analysis was done with Fisher's exact and t-tests. RESULTS: Of all, 77.1% (111/144) had normoalbuminuria and 22.9% (33/144) had microalbuminuria. Of 33 microalbuminuric women, the mean blood pressure was significantly higher in those who subsequently developed pre-eclampsia (P<0.001). The mean ACR (mg/g) in this cohort was 60.6±29.4. The mean ACR (mg/g) in women who subsequently developed pre-eclampsia was significantly higher than in women who remained normotensive (P=0.003). Of 33 microalbuminuric women, 12 (36.4%) developed pre-eclampsia, and eight (24.2%) had preterm births. The mean birthweight (kg±standard deviation) was significantly lower in the microalbuminuria group (2.45±0.6) as compared to the normoalbuminuria group (2.8±0.37), P<0.001. CONCLUSION: Microalbuminuria in mid-pregnancy may be a significant predictor of development of subsequent pre-eclampsia, preterm birth and low-birthweight babies.

Advanced glycation end products and diabetic retinopathy.

Studies have established hyperglycemia as the most important factor in the progress of vascular complications. Formation of advanced glycation end products (AGEs) correlates with glycemic control. The AGE hypothesis proposes that hyperglycemia contributes to the pathogenesis of diabetic complications including retinopathy. However, their role in diabetic retinopathy remains largely unknown. This review discusses the chemistry of AGEs formation and their patho-biochemistry particularly in relation to diabetic retinopathy. AGEs exert deleterious effects by acting directly to induce cross-linking of long-lived proteins to promote vascular stiffness, altering vascular structure and function and interacting with receptor for AGE, to induce intracellular signaling leading to enhanced oxidative stress and elaboration of key proinflammatory and prosclerotic cytokines. Novel anti-AGE strategies are being developed hoping that in next few years, some of these promising therapies will be successfully evaluated in clinical context aiming to reduce the major economical and medical burden caused by diabetic retinopathy.