The impact of a second embryo biopsy for preimplantation genetic testing for monogenic diseases (PGT-M) with inconclusive results on pregnancy potential: results from a matched case-control study.

Purpose: To evaluate whether a second biopsy, following a first diagnostic failure on blastocysts tested for preimplantation genetic testing for monogenic diseases (PGT-M), allows to obtain genetic diagnosis and to what extent this procedure can influence clinical pregnancy and live birth rates compared to the PGT-M process with a successful genetic diagnosis from the first biopsy.

Methods: Embryos from women who underwent PGT-M in an infertility centre and who had been transferred after two biopsies for genetic analysis (n = 27) were matched in a 1:1 ratio accordingly to women's age (± 1 year) and fertility status (fertile vs infertile), as well as with the study period, with embryos who were transferred after receiving a conclusive PGT result straight after the first biopsy (n = 27). The main evaluated outcome was clinical pregnancy rate following embryo transfers in which healthy embryos were transferred after only one biopsy and those in which an embryo was transferred after being re-biopsied.

Effects of weight loss in metabolically healthy obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet.

Weight loss in metabolically healthy obese (MHO) subjects may result in deterioration of cardio-metabolic risk profile. We analyzed the effects of weight loss induced by laparoscopic adjustable gastric banding (LAGB) on cardio-metabolic risk factors in MHO and insulin resistant obese (IRO) individuals. This study included 190 morbidly obese non-diabetic subjects.

The glial glutamate transporter 1 (GLT1) is expressed by pancreatic beta-cells and prevents glutamate-induced beta-cell death.

Glutamate is the major excitatory neurotransmitter of the central nervous system (CNS) and may induce cytotoxicity through persistent activation of glutamate receptors and oxidative stress. Its extracellular concentration is maintained at physiological concentrations by high affinity glutamate transporters of the solute carrier 1 family (SLC1). Glutamate is also present in islet of Langerhans where it is secreted by the α-cells and acts as a signaling molecule to modulate hormone secretion.

Oxidative stress biomarkers and chromogranin A in uremic patients: effects of dialytic treatment.

Objective: To evaluate oxidative stress in uremia and dialysis and chromogranin A, a stress hormone that could be related to oxidative processes.

Methods: Plasma oxidative stress biomarkers (-SH, 8-OHdG, and ox-LDL) and chromogranin A were measured in 89 outpatients (21 uremic patients, 17 in peritoneal dialysis, and 51 in haemodialysis), and in 18 subjects with normal renal function.

Results: -SH groups were significantly reduced in heamodialysis, peritoneal, and uremic patients as compared with the control group (p=0.

Proteomics reveals novel oxidative and glycolytic mechanisms in type 1 diabetic patients' skin which are normalized by kidney-pancreas transplantation.

Background: In type 1 diabetes (T1D) vascular complications such as accelerated atherosclerosis and diffused macro-/microangiopathy are linked to chronic hyperglycemia with a mechanism that is not yet well understood. End-stage renal disease (ESRD) worsens most diabetic complications, particularly, the risk of morbidity and mortality from cardiovascular disease is increased several fold.

Methods And Findings: We evaluated protein regulation and expression in skin biopsies obtained from T1D patients with and without ESRD, to identify pathways of persistent cellular changes linked to diabetic vascular disease.

Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats.

Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a physiological tetrapeptide hydrolysed by ACE (angiotensin-converting enzyme). In experimental models of hypertension, Ac-SDKP has antifibrotic effects in the heart; however, the role of Ac-SDKP in diabetic cardiomyopathy is currently unknown. The aim of the present study was to evaluate the effect of Ac-SDKP on cardiac systolic and diastolic function, and interstitial and perivascular fibrosis in the heart of diabetic rats.

Ten-year quality control of a semiautomated procedure of cord blood unit volume reduction.

Background: Volume reduction of cord blood units decreases the cost of cryogenic storage. This study reports the analysis of a 10-year quality control program of a semiautomated cord blood volume reduction procedure.

Study Design And Methods: Cord blood was collected in a plastic bag containing 29 mL citrate-phosphate-dextrose, centrifuged at 2124 x g for 12 minutes, and processed with a semiautomated device.

The crosstalk between insulin and renin-angiotensin-aldosterone signaling systems and its effect on glucose metabolism and diabetes prevention.

Essential hypertension is an insulin resistant state. Early insulin signaling steps are impaired in essential hypertension and a large body of data suggests that there is a crosstalk at multiple levels between the signal transduction pathways that mediate insulin and angiotensin II actions. At the extracellular level the angiotensin converting enzyme (ACE) regulates the synthesis of angiotensin II and bradykinin that is a powerful vasodilator.

Elevated concentrations of liver enzymes and ferritin identify a new phenotype of insulin resistance: effect of weight loss after gastric banding.

Background: Several studies have associated elevated liver enzymes (LFTs), obesity, and type 2 diabetes (T2DM), and a link has been established between insulin resistance (IR) and elevated ferritin concentrations. We examined the relationship between LFTs, ferritin, and IR in morbid obese subjects and the effect of weight loss after bariatric surgery.

Methods: We measured liver enzymes, ferritin, insulin resistance, and glucose tolerance (by OGTT) in 159 morbid obese subjects (BMI = 44.

Disproportionate hyperproinsulinemia, beta-cell restricted prohormone convertase 2 deficiency, and cell cycle inhibitors expression by human islets transplanted into athymic nude mice: insights into nonimmune-mediated mechanisms of delayed islet graft failure.

To learn more about nonimmune-mediated islet graft failure, we transplanted different preparations (preps) of isolated human islets under the kidney capsule of streptozotocin (STZ)-diabetic nude mice. One month after the implantation of 1,000 or 2,000 islets, grafts were harvested for morphological, immunohistochemical, and ultrastructural analysis. Only a single islet prep cured the diabetes out of all the recipients, while the remaining preps showed only partial function after the implantation of 2,000 islets.

The multi-faceted cross-talk between the insulin and angiotensin II signaling systems.

Insulin and angiotensin II are hormones that play pivotal roles in the control of two vital and closely related systems, the metabolic and the circulatory systems, respectively. A failure in the proper action of each of these hormones results, to a variable degree, in the development of two highly prevalent and commonly overlapping diseases-diabetes mellitus and hypertension. In recent years, a series of studies has revealed a tight connection between the signal transduction pathways that mediate insulin and angiotensin II actions in target tissues.

Effect of gonadotropins during in vitro maturation of feline oocytes on oocyte-cumulus cells functional coupling and intracellular concentration of glutathione.

Information about the mechanisms of meiotic arrest and resumption of meiosis in feline oocytes is still limited. The aim of this study was to investigate the effect of the presence of gonadotropins during IVM, on meiotic progression in relation to the status of gap junction mediated communications between oocyte and cumulus cells, to the cAMP intracellular content, and to the intra-oocyte concentration of glutathione (GSH) in feline oocytes. Our results indicated that about 50% of cumulus-oocyte complexes (COCs) showed functionally open communications at the time of collection, while the remainder were partially or totally closed.

Laparoscopic gastric banding prevents type 2 diabetes and arterial hypertension and induces their remission in morbid obesity: a 4-year case-controlled study.

Objective: Lifestyle modifications and pharmacological interventions can prevent type 2 diabetes in obese subjects with impaired glucose tolerance. The aim of this study was to compare laparoscopic adjustable gastric banding (LAGB) and conventional diet (No-LAGB) in the prevention (primary intervention study; 56 vs. 29 patients) and remission (secondary intervention study; 17 vs.

Morphological and functional differences in haemostatic axis between kidney transplanted and end-stage renal disease patients.

End-stage renal disease (ESRD) is characterized by several atherothrombotic abnormalities, and kidney transplant seems to improve most of them. However, because it is not clear which mechanism is responsible for such improvement, our purpose was to clarify that point.We conducted a cross sectional study involving 30 ESRD patients, 30 ESRD kidney-transplanted patients (Ktx) and 30 healthy controls (C) to evaluate platelet morphology and function, atherothrombotic profile, endothelial abnormalities and cytokine levels involved in the insulin resistance/endothelial dysfunction.

C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance.

Objective: The C-174G promoter polymorphism of the interleukin (IL)-6 gene was found to influence transcriptional activity and plasma IL-6 levels in humans. We addressed the question of whether the C-174G IL-6 polymorphism contributes to variation of insulin sensitivity.

Research Design And Methods: Two cohorts of subjects were genotyped.

Impact of common polymorphisms in candidate genes for insulin resistance and obesity on weight loss of morbidly obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet.

Context: It is unknown whether genetic factors that play an important role in body weight homeostasis influence the response to laparoscopic adjustable gastric banding (LAGB).

Objective: We investigated the impact of common polymorphisms in four candidate genes for insulin resistance on weight loss after LAGB.

Design: The design was a 6-month follow-up study.

Circulating leptin correlates with left ventricular mass in morbid (grade III) obesity before and after weight loss induced by bariatric surgery: a potential role for leptin in mediating human left ventricular hypertrophy.

Context: Obesity is frequently associated with left ventricular hypertrophy, even when uncomplicated by hypertension or diabetes mellitus. Left ventricular hypertrophy is an important risk factor for congestive heart failure.

Objective: The objective of this study was to evaluate the relationship between leptin and left ventricular mass in uncomplicated, morbid (grade 3) obesity and the existence of leptin receptors and intracellular signaling proteins in the human heart.

The -866A/A genotype in the promoter of the human uncoupling protein 2 gene is associated with insulin resistance and increased risk of type 2 diabetes.

Uncoupling protein (UCP)-2 is a member of the mitochondrial inner membrane carriers that uncouple pro-ton entry in the mitochondrial matrix from ATP synthesis. The -866G/A polymorphism in the UCP2 gene, which enhances its transcriptional activity, was associated with enhanced risk for type 2 diabetes in obese subjects. We addressed the question of whether the -866G/A polymorphism contributes to variation in insulin sensitivity by genotyping 181 nondiabetic offspring of type 2 diabetic patients.

Chronic hyperglycemia impairs insulin secretion by affecting insulin receptor expression, splicing, and signaling in RIN beta cell line and human islets of Langerhans.

Recent evidence suggests that insulin signaling through the insulin receptor A type (Ex11-), regulates insulin gene transcription. Because chronic hyperglycemia negatively affects insulin receptor function and regulates alternative splicing of the insulin receptor, we inquired whether chronic exposure of pancreatic beta-cells to high glucose results in alterations in insulin signaling due to changes in insulin receptor expression and relative abundance of its spliced isoforms. Our results demonstrate that the insulin receptor is localized in insulin secretory vescicles in human pancreatic beta-cells.

Obesity modulates the expression of haptoglobin in the white adipose tissue via TNFalpha.

Increase in adipose mass results in obesity and modulation of several factors in white adipose tissue (WAT). Two important examples are tumor necrosis factor alpha (TNFalpha) and leptin, both of which are upregulated in adipose tissue in obesity. In order to isolate genes differentially expressed in the WAT of genetically obese db/db mice compared to their lean littermates, we performed RNA fingerprinting and identified haptoglobin (Hp), which is significantly upregulated in the obese animals.