Molecular dynamics studies on the NMR and X-ray structures of rabbit prion protein wild-type and mutants

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep, goats, mice, humans, chimpanzees, hamsters, cattle, elks, deer, minks, cats, chicken, pigs, turtles, etc. These neurodegenerative diseases are caused by the conversion from a soluble normal cellular protein into insoluble abnormally folded infectious prions and the conversion is believed to involve conformational change from a predominantly alpha-helical protein to one rich in beta-sheet structure. Such conformational changes may be amenable to study by molecular dynamics (MD) techniques. For rabbits, classical studies show they have a low susceptibility to be infected, but in 2012 it was reported that rabbit prion can be generated (though not directly) and the rabbit prion is infectious and transmissible (Proceedings of the National Academy of Sciences USA 109(13): 5080-5). This paper studies the NMR and X-ray molecular structures of rabbit prion protein wild-type and mutants by MD techniques, in order to understand the specific mechanism of rabbit prion protein and rabbit prions.Comment: (The 2nd version of arXiv1304.7633

The serum vaspin levels are reduced in Japanese chronic hemodialysis patients

Background: Visceral adipose tissue-derived serine proteinase inhibitor (vaspin) is an adipokine identified in genetically obese rats that correlates with insulin resistance and obesity in humans. Recently, we found that 7% of the Japanese population with the minor allele sequence (A) of rs77060950 exhibit higher levels of serum vaspin. We therefore evaluated the serum vaspin levels in Japanese chronic hemodialysis patients. Methods: Healthy Japanese control volunteers (control; n = 95, 49.9 +/- 6.91 years) and Japanese patients undergoing hemodialysis therapy (HD; n = 138, 51.4 +/- 10.5 years) were enrolled in this study, and serum samples were subjected to the human vaspin RIA system. Results: The measurement of the serum vaspin levels demonstrated that a fraction of control subjects (n = 5) and HD patients (n = 11) exhibited much higher levels (> 10 ng/ml; Vaspin(High) group), while the rest of the population exhibited lower levels (< 3 ng/ml; Vaspin(Low) group). By comparing the patients in the Vaspin(Low) group, the serum vaspin levels were found to be significantly higher in the control subjects (0.87 +/- 0.24 ng/ml) than in the HD patients (0.32 +/- 0.15 ng/ml) (p < 0.0001). In the stepwise regression analyses, the serum creatinine and triglyceride levels were found to be independently and significantly associated with the vaspin concentrations in all subjects. Conclusions: The creatinine levels are negatively correlated with the serum vaspin levels and were significantly reduced in the Japanese HD patients in the Vaspin(Low) group

N-terminal-pro-brain natriuretic peptide is decreased in insulin dependent gestational diabetes mellitus: a prospective cohort trial

<p>Abstract</p> <p>Background</p> <p>N-terminal-pro-brain natriuretic peptide (NT-proBNP) is elevated in gestational hypertension and preeclampsia. This trial aimed to generate data for gestational diabetes mellitus patients, who are at risk to develop these complications.</p> <p>Methods</p> <p>We have measured NT-proBNP in 223 otherwise healthy women between gestational week 24 and 32 referred to the outpatient diabetes unit in a cross-sectional study.</p> <p>Results</p> <p>88 control subjects, 45 patients with indication for medical nutrition therapy (MNT) alone and 90 patients who required insulin therapy were included. Groups of women were comparable regarding gestational week. Body mass index before pregnancy and at blood draw was significantly higher in subjects with insulin dependent gestational diabetes mellitus compared to MNT controlled gestational diabetes mellitus. NT-proBNP was significantly lower in patients with insulin dependent gestational diabetes mellitus (35 ± 25 pg/ml) compared to controls (53 ± 43 pg/ml, p = 0.012).</p> <p>Conclusions</p> <p>NT-proBNP is within the reference range of normal subjects in women with gestational diabetes mellitus. Differences in body mass index, changes in glomerular filtration rate and haemodynamics may explain lower NT-proBNP concentrations in insulin dependent gestational diabetes mellitus. A false negative interpretation needs to be considered in these women.</p

Fetuin-A Characteristics during and after Pregnancy: Result from a Case Control Pilot Study

Objective. Fetuin-A has been associated with gestational diabetes mellitus (GDM). We investigated fetuin-A levels during and after pregnancy in women with GDM. Fetuin-A measurements were performed in 10 women with GDM and 10 age and body mass index (BMI) matched healthy pregnant women. All women underwent an oral glucose tolerance test (OGTT) in and 3 months after gestation. Results. Fasting fetuin-A correlated with BMI in women with former GDM (r = 0.90, P < 0.0001) but showed no association with parameters of glucose tolerance in women with GDM or post-GDM. GDM featured significantly lower insulin sensitivity and higher insulin and C-peptide secretion profiles compared to NGT during pregnancy (P < 0.05). Fasting and postprandial fetuin-A did not differ between groups, neither during nor after pregnancy. Conclusion. Fetuin-A is not influenced by glucose tolerance during or after pregnancy or acute glucose elevations following glucose ingestion in young women, but closely relates to BMI early postpartum

Circulating progranulin levels in women with gestational diabetes mellitus and healthy controls during and after pregnancy

ObjectiveProgranulin (PGRN) was recently introduced as a novel marker of chronic inflammatory response in obesity and type 2 diabetes capable of directly affecting the insulin signaling pathway. This study aimed to investigate the role of PGRN in gestational diabetes mellitus (GDM), which is regarded as a model for early type 2 diabetes.MethodsPGRN serum levels were measured in 90 pregnant women (45 GDM and 45 normal glucose tolerance (NGT)). In addition, PGRN was measured during a 2-h, 75 g oral glucose tolerance test in 20 pregnant women (ten GDM and ten NGT) and in 16 of thempost partum(ten GDM and six NGT).ResultsPGRN concentrations were significantly higher in pregnant women compared withpost partumlevels (536.79±31.81 vs 241.53±8.86,P<0.001). Multivariate regression analyses showed a strong positive correlation of PGRN with estrogen and progesterone. The insulinogenic index, a marker of early insulin secretion, displayed a positive correlation with PGRN, both during and after pregnancy (R=0.47,P=0.034;R=0.63,P=0.012). HbA1c and the oral glucose insulin sensitivity index showed significantpost partumassociations with PGRN (R=0.43,P=0.049;R=−0.65,P=0.009).ConclusionsPGRN concentrations are markedly lower after pregnancy regardless of the gestational glucose tolerance state. PGRN levelsper sedo not discriminate between mild GDM and NGT in pregnant women. Therefore, the development of GDM appears to be due to impaired β-cell function that is not related to PGRN effect

Inflammation and endothelial activation in benign prostatic hyperplasia and prostate cancer

PURPOSE: Emerging insights underline a link among chronic inflammation and endothelial activation with benign prostatic hyperplasia (BPH) and prostate cancer (PCa). We aim to investigate whether specific plasma markers of inflammation and endothelial activation allow to discriminate BPH and PCa. MATERIALS AND METHODS: Fifteen patients affected by BPH, 15 by PCa and 15 controls, were enrolled. Interleukin-6 (IL-6), CD40 ligand (CD40L), endothelial-selectin (E-selectin), platelet-selectin (P-selectin), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured. RESULTS: In systemic blood samples, IL-6 has been found increased in patients affected by BPH (4.25 ± 0. pg/mL) and PCa (5.08 ± 0.24) respect to controls (2.62 ± 0.34; p < 0.05). CD40L was higher in BPH (4.25 ± 0.65 ng/mL; p < 0.05) than in control (2.31 ± 0.20) and PCa group (2.60 ± 0.56). E-selectin, P-selectin and VCAM-1 did not show any significant difference. Higher levels of ICAM-1 were detected in patients with PCa (573.04 ± 52.23) and BPH (564.40 ± 74.67) than in the controls (215.30 ± 11.53 ng/mL; p < 0.05). In local blood samples, IL-6 has been found significantly increased in PCa in comparison with patients with BPH; there was no difference in CD40L, E-selectin, P-selectin, VCAM-1 ed ICAM-1. CONCLUSIONS: Changes in inflammation and endothelial activation markers may be not considered to be of value in discriminating BPH and PCa