Cardiovascular disease risk in young Indian women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with significant risk factors for cardiovascular disease (CVD) like insulin resistance, hyperinsulinism, hypertension and dyslipidemia. We studied CVD risk in young women (18–35 years age) with PCOS using carotid intima media thickness (CIMT) and brachial artery flow mediated dilation (FMD) which are markers of subclinical atherosclerosis. Fifty women with PCOS (age: 24.3?±?4 years; body mass index [BMI]: 24.6?±?4?kg/m²) were compared with 50 age and BMI matched healthy controls (age: 24.6?±?5 years; BMI: 23.9?±?4?kg/m²). CIMT was significantly higher (0.55?±?0.09?mm versus 0.40?±?0.1?mm, p value <0.0001) and FMD was significantly lower (9.39?±?4.36% versus 13.89?±?4.77%, p value <0.0001) in cases as compared to controls. These differences in CIMT and FMD remained significant when subgroup were analyzed, obese PCOS versus obese controls and non obese PCOS versus non-obese controls. In stepwise linear regression PCOS was associated with CIMT and FMD independent of age, BMI and blood pressure. Young women with PCOS irrespective of their BMI have evidence for increased CVD risk as shown by increased CIMT and a lower FMD.     

Clathrin‐Mediated Endocytosis of Gold Nanoparticles In Vitro

Gold nanoparticles (AuNPs) have potential biomedical and scientific applications. In this study, we evaluated the uptake and internalization of FBS‐coated 20 nm AuNPs into lung fibroblasts and liver cells by different microscopy techniques. AuNP aggregates were observed inside MRC5 lung fibroblasts and Chang liver cells under light microscopy, especially after enhancement with automegallography. Clusters of AuNPs were observed to be adsorbed on the cell surface by scanning electron microscopy. Ultrathin sections showed that AuNPs were mainly enclosed within cytoplasmic vesicles when viewed under transmission electron microscopy. We also investigated the mechanism of uptake for AuNPs, using endocytosis inhibitors and quantification of Au with inductively coupled plasma mass spectrometry. Cells treated with concanavalin A and chlorpromazine showed significant decrease of Au uptake in MRC5 lung fibroblasts and Chang liver cells, respectively, implying that the uptake of AuNPs was facilitated by clathrin‐mediated endocytosis. It would therefore appear that uptake of 20 nm AuNPs in both cell types with different tissues of origin, was dependent upon clathrin‐mediated endocytosis. Anat Rec, 298:418–427, 2015. © 2014 Wiley Periodicals, Inc.     

Hyaluronic acid controls the uptake pathway and intracellular trafficking of an octaarginine-modified gene vector in CD44 positive- and CD44 negative-cells

The cellular uptake pathway for a gene vector is an important factor in transgene expression. We previously constructed an original gene vector, multifunctional envelope-type nano device (MEND). The use of octaarginine (R8), a cell-penetrating peptide dramatically enhanced the transfection activity of the MEND since efficient cellular uptake via macropinocytosis, while the R8 should overcome its poor cell selectivity. Here we prepared an R8-MEND equipped with GALA (a peptide for endosomal escape) (R8/GALA-MEND) coated with hyaluronic acid (HA) (HA-R8/GALA-MEND), a natural ligand for cancer cells overexpressing CD44. We investigated the cellular uptake pathway of the HA-R8/GALA-MEND and the R8/GALA-MEND using HCT116 cells overexpressing CD44. Both carriers were taken up by cells mainly via macropinocytosis, whereas only the HA-R8/GALA-MEND was partially internalized into cells via a CD44-mediated pathway. Investigation of transgene expression showed that the HA-R8/GALA-MEND had a high transfection activity in HCT116 cells via both macropinocytotic and CD44-mediated pathways. On the other hand, the value for the HA-R8/GALA-MEND was significantly decreased compared with the value for the R8/GALA-MEND in NIH3T3 cells (CD44-negative cells). These findings indicate that the HA-coating controls the intracellular pathway for R8-modified nanocarriers, and that a CD44-mediated pathway is an important route for transgene expression.     

Successful ABO-incompatible heart transplantation in a child despite blood-group sensitization after ventricular assist device support

Abstract:  In the first two yr of life blood-group incompatible (ABO-incompatible) heart transplantation can be performed leading to immune tolerance to donor blood group. Antibody titers should be below 1:4. VAD use is correlated with sensitization toward blood-group antigens. A boy was diagnosed with dilated cardiomyopathy at nine months of age and listed for 0-compatible transplantation. Progressive heart failure required implantation of a left VAD. His listing was extended for ABO-incompatible transplantation despite antibody titers of 1:32 anti-A and 1:8 anti-B. After 26 days on VAD, he was transplanted with a B donor heart. No hyperacute or acute rejection occurred in 12 months post-transplant. Anti-B antibodies rose to a maximum of 1:2. No use of rituximab or plasmapheresis was required. There are no signs of graft vasculopathy. This indicates that inclusion criteria for ABO-incompatible transplantation may be extended to immediate cases. This is the first case with a healthy immune system to show signs of tolerance development after ABO-incompatible heart transplantation with increased prior antibody titers and without specific treatment.     

Management of Vasovagal Syncope

Vasovagal syncope is a common disorder of autonomic cardiovascular regulation that can be very disabling and result in a significant level of psychosocial and physical limitations. The optimal approach to treatment of patients with vasovagal syncope remains uncertain. Although many different types of treatment have been proposed and appear effective based largely on small nonrandomized studies and clinical series, there is a remarkable absence of data from large prospective clinical trials. However, based on currently available data, the pharmacologic agents most likely to be effective in the treatment of patients with vasovagal syncope include beta blockers, fludrocortisone, and alpha-adrenergic agonists. In this article, we provide a summary of the various therapeutic options that have been proposed for vasovagal syncope and review the clinical studies that form the basis of present therapy for this relatively common entity.     

Selective Vagal Denervation of the Sinus and Atrioventricular Nodes, Guided by Vagal Reflexes Induced by High Frequency Stimulation, to Treat Refractory Neurally Mediated Syncope

A 15-year-old female patient presented with frequent episodes of vasovagal syncope refractory to non-pharmacological and pharmacological measures. Two tilt-table tests performed before and after conventional therapy were positive and reproduced the patient's clinical symptoms. Selective vagal denervation, guided by HFS, was performed. Six radiofrequency pulses were applied on the left and right sides of the interatrial septum, abolishing vagal responses at these locations. Basal sinus node and Wenckebach cycle lengths changed significantly following ablation. A tilt test performed after denervation was negative and revealed autonomic tone modification. The patient reported significant improvement in quality of life and remained asymptomatic for 9 months after denervation. After this period, three episodes of NMS occurred during a 4-month interval and a tilt test performed 11 months after the procedure demonstrated vagal activity recovery.