Gender differences in insulin and C-peptide concentrations at birth using cord blood collection

ABSTRACT Objective: To study gender differences in insulin and C-peptide concentrations at birth using cord blood collection. Subjects and methods: This study was conducted in a maternity hospital, in Jammu province of Jammu and Kashmir, India. All women with pregnancy who were hospitalized for delivery were followed. All pregnant ladies who had no medical condition affecting insulin levels, as per history and routine antenatal blood testing, were included in the study. The test for cord plasma insulin and C-peptide was done in 60 (30 males) full-term (≥ 37 completed weeks) normal delivery babies within 4 hours of the collection of samples using the electro-chemiluminescence immunoassay (ECLIA) on Roche elecsys module immunoassay analyzer. Weight of the babies was taken immediately after birth using digital scales. Results: Cord plasma insulin and C-peptide measured in EDTA were compared between boys and girls and also related to birth weight. Girls were lighter (2,830 ± 37 vs. 3,236 ± 46 g; p = < 0.001) but had higher cord insulin (16.48 ± 4.88 vs. 10.53 ± 4.04 µU/mL; p = < 0.001), and C-peptide (2.47 ± 0.66 vs. 0.834 ± 0.26 ng/mL; p = < 0.001) concentrations than newborn boys. Conclusion: Female newborn babies have higher cord plasma insulin and C-peptide concentrations than male newborns, despite being smaller, suggesting intrinsic insulin resistance in girls. Arch Endocrinol Metab. 2016;60(3):264-

KDM2A represses transcription of centromeric satellite repeats and maintains the heterochromatic state

Heterochromatin plays an essential role in the preservation of epigenetic information, the transcriptional repression of repeti- tive DNA elements and inactive genes, and the proper segregation of chromosomes during mitosis. Here we identify KDM2A, a JmjC-domain containing histone demethylase, as a heterochro- matin-associated and HP1-interacting protein that promotes HP1 localization to chromatin. We show that KDM2A is required to maintain the heterochromatic state, as determined using a candidate-based approach coupled to an in vivo epigenetic reporter system. Remarkably, a parallel and independent siRNA screen also detected a role for KDM2A in epigenetic silencing. Moreover, we demonstrate that KDM2A associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Dissecting the relationship between heterochromatin and centromeric RNA transcription is the basis of ongoing studies. We demonstrate that forced expression of these satellite RNA transcripts compromise the heterochromatic state and HP1 localization to chromatin. Finally, we show that KDM2A is required to sustain centromeric integ- rity and genomic stability, particularly during mitosis. Since the disruption of epigenetic control mechanisms contributes to cellular transformation, these results, together with the low levels of KDM2A found in prostate carcinomas, suggest a role for KDM2A in cancer development

The association between energy-adjusted dietary inflammatory index and metabolic syndrome and its mediatory role for cardiometabolic diseases: a prospective cohort study

BackgroundMetabolic syndrome (MetS) is a collection of medical conditions that elevate the chance of cardiovascular disease. An unhealthy diet is a major risk factors for MetS through different mechanisms, especially systemic chronic inflammation.ObjectiveThis study aimed to investigate the effect of dietary inflammatory potential on MetS incidence and the role of MetS in the association between Energy-adjusted dietary inflammatory index (E-DII) and cardiometabolic diseases.MethodsIn this prospective cohort study, 10,138 participants were recruited. All participants were divided into MetS or non-MetS groups based on the Adult Treatment Panel III criteria. The E-DII was used to assess the inflammatory potential of diet. After excluding the participants with MetS at baseline, 2252 individuals were followed for 5 years (longitudinal phase), and the effect of E-DII on MetS incidence was investigated using logistic regression models (p-value <0.05).ResultsThe cohort’s mean age (45.1% men) was 48.6 ± 10.0 years. E-DII ranged from −6.5 to 5.6 (mean: −0.278 ± 2.07). Higher E-DII score had a 29% (95%CI: 1.22–1.36) increased risk for incidence of MetS and its components during five-year follow-up. Also, E-DII was significantly associated with the prevalence of MetS (OR = 1.55, 95%CI: 1.51–1.59). Among MetS components, E-DII had the strongest association with waist circumference in the cross-sectional study (OR = 2.17, 95%CI: 2.08–2.25) and triglyceride in the longitudinal study (OR = 1.19, 95%CI: 1.13–1.25). The association between E-DII and MetS was consistent in both obese (OR = 1.13, 95%CI:1.05–1.21) and non-obese (OR = 1.42, 95%CI: 1.27–1.60) individuals and stronger among non-obese participants. Additionally, MetS mediated the association between E-DII and hypertension, diabetes, and myocardial infarction.ConclusionIn conclusion, a pro-inflammatory diet consumption is associated with a higher risk of MetS and its components. Furthermore, a pro-inflammatory diet increases the risk of cardiometabolic diseases. The higher E-DII had a stronger association with MetS, even among normal-weight individuals

Regulation of calpain-1 signaling in platelets.

Regulation of calpain-1 signaling in platelets

Levosulpiride and serum prolactin levels

Levosulpiride is the levorotatory enantiomer of sulpiride used in dyspeptic syndromes of various etiologies. The prokinetic effect of levosulpiride is mediated through the blockade of enteric inhibitory dopaminergic type 2 (D2) receptors. The antagonism of central D2 receptors leads to both therapeutic (e.g. antiemetic effect due to D2 receptor blockade in the chemoreceptor trigger zone) and adverse (including hyperprolactinemia) effects. Dopamine is the main endogenous inhibitor of prolactin synthesis and secretion in the anterior pituitary. Levosulpiride causes significant elevation of serum prolactin levels in significant number of patients. The resultant hyperprolactinemia often manifests as distressing menstrual abnormalities and galactorrhoea in females. A significant number of patients who use levosulpiride develop serum prolactin levels of > 200 ng/mL that goes against the classical textbook teaching where pituitary tumor is supposed to be the mostly likely cause. Careful drug history in patients presenting with high serum prolactin levels will be of great help in reaching the exact diagnosis and avoiding unnecessary brain imaging

Effects of Metabolic Dysfunction-Associated Steatotic Liver Disease on Bone Density and Fragility Fractures: Associations and Mechanisms

Metabolic dysfunction-associated steatotic liver disease (MASLD) has profound adverse effects on bone health and homeostasis. MASLD appears to be associated with changes in bone mineral density (BMD) and fracture rate. However, the data are ambiguous and conflicting. Although several studies have shown that children and adolescents with MASLD have decreased BMD, the data on the prevalence of fragility fractures among children are scarce. In adults, increasing evidence suggests that MASLD decreases BMD and increases the risk of fragility fractures, which appears to be due to deterioration of bone architecture in addition to a decrease in BMD. Effects of MASLD on bone health may also be age- and race-specific. MASLD does not seem to increase fracture risk in children and adolescents but increases the risk of fractures in elderly men, especially those of Asian origin. From a mechanistic perspective, bone remodeling is a continuous process between osteoblasts (bone-forming) and osteoclasts (bone-resorbing), with any imbalance resulting in metabolic bone disease. In individuals with MASLD, loss of anabolic insulin receptor signaling (insulin resistance) in osteoblasts and increased receptor activator of nuclear factor κB (RANK)/RANK ligand signaling in osteoclasts (proinflammatory cytokines) swings the pendulum toward accelerated bone loss. These processes are further complicated by the concomitant presence of obesity, type 2 diabetes mellitus, or sarcopenia in individuals with MASLD. This study reviews the current literature associated with the effects of MASLD on BMD and fragility fractures in children/adolescents and adults. This review also discusses the pathomechanisms that link MASLD with changes in BMD and fragility fractures

Hemoglobin E disease and glycosylated hemoglobin

Glycosylated hemoglobin (HbA1C) is a routinely measured parameter to monitor long-term glycemic control in people with diabetes mellitus. The presence of hemoglobin (Hb) variants can affect the accuracy of HbA1C methods. Hb E variant is the most common Hb variant in South-east Asia and North-east India. In the presence of Hb E, HbA1C may not be detectable by ion-exchange chromatography (high-pressure liquid chromatography), but may be estimated by immunoassay technique and boronate affinity chromatography. However, the result may be underestimated when correlated with plasma glucose and serum fructosamine levels. Clinicians should be aware of this limitation of HbA1C estimation in patients with Hb E and other Hb variants

brief report Gender differences in insulin and C-peptide concentrations at birth using cord blood collection

ABSTRACT Objective: To study gender differences in insulin and C-peptide concentrations at birth using cord blood collection. Subjects and methods: This study was conducted in a maternity hospital, in Jammu province of Jammu and Kashmir, India. All women with pregnancy who were hospitalized for delivery were followed. All pregnant ladies who had no medical condition affecting insulin levels, as per history and routine antenatal blood testing, were included in the study. The test for cord plasma insulin and C-peptide was done in 60 (30 males) full-term (≥ 37 completed weeks) normal delivery babies within 4 hours of the collection of samples using the electro-chemiluminescence immunoassay (ECLIA) on Roche elecsys module immunoassay analyzer. Weight of the babies was taken immediately after birth using digital scales. Results: Cord plasma insulin and C-peptide measured in EDTA were compared between boys and girls and also related to birth weight. Girls were lighter (2,830 ± 37 vs. 3,236 ± 46 g; p = < 0.001) but had higher cord insulin (16.48 ± 4.88 vs. 10.53 ± 4.04 µU/mL; p = < 0.001), and C-peptide (2.47 ± 0.66 vs. 0.834 ± 0.26 ng/mL; p = < 0.001) concentrations than newborn boys. Conclusion: Female newborn babies have higher cord plasma insulin and C-peptide concentrations than male newborns, despite being smaller, suggesting intrinsic insulin resistance in girls

NS5A Promotes Constitutive Degradation of IP3R3 to Counteract Apoptosis Induced by Hepatitis C Virus

FBXL2 targets IP3R3 for ubiquitin-mediated degradation to limit Ca2+ flux to mitochondria and, consequently, apoptosis. Efficient replication of hepatitis C virus (HCV) requires geranylgeranylation of FBXL2. Here, we show that the viral protein NS5A forms a trimeric complex with IP3R3 and FBXL2, unmasking IP3R3’s degron in the absence of inositol 1,4,5-trisphosphate (IP3) stimulation. FBXL2 knockdown or expression of a stable IP3R3 mutant causes persistent Ca2+ flux and sensitizes cells to apoptosis, resulting in the inhibition of viral replication. Importantly, the effect of FBXL2 silencing is rescued by depleting IP3R3, but not p85β another established FBXL2 substrate, indicating that the anti-HCV effect of FBXL2 knockdown is largely due to IP3R3 stabilization. Finally, disruption of the FBXL2-NS5A-IP3R3 complex using somatic cell genetics or pharmacologic inhibition results in IP3R3 stabilization and suppression of HCV replication. This study reveals an IP3-independent molecular mechanism through which HCV promotes IP3R3 degradation, thereby inhibiting virus-induced apoptosis and establishing chronic infection. Kuchay et al. show that the HCV NS5A protein forms a complex with IP3R3 and FBXL2 and promotes constitutive FBXL2-mediated degradation of IP3R3. IP3R3 degradation inhibits calcium flux, mitochondrial calcium overload, and apoptosis. Thus, NS5A contributes to a cellular environment that is permissive for chronic HCV infection

“Excess gooD can be Dangerous”. A case series of iatrogenic symptomatic hypercalcemia due to hypervitaminosis D

Vitamin D is increasingly recognized to have several beneficial effects. Its toxicity, causing hypercalcemia, is considered as extremely rare. We report case series of 15 patients (most of them being elderly subjects) with iatrogenic symptomatic hypercalcemia in whom toxicity occurred due to empirical excessive administration of vitamin D by oral and parenteral rout