Random-coil behavior and the dimensions of chemically unfolded proteins

Spectroscopic studies have identified a number of proteins that appear to retain significant residual structure under even strongly denaturing conditions. Intrinsic viscosity, hydrodynamic radii, and small-angle x-ray scattering studies, in contrast, indicate that the dimensions of most chemically denatured proteins scale with polypeptide length by means of the power-law relationship expected for random-coil behavior. Here we further explore this discrepancy by expanding the length range of characterized denatured-state radii of gyration (R(G)) and by reexamining proteins that reportedly do not fit the expected dimensional scaling. We find that only 2 of 28 crosslink-free, prosthetic-group-free, chemically denatured polypeptides deviate significantly from a power-law relationship with polymer length. The R(G) of the remaining 26 polypeptides, which range from 16 to 549 residues, are well fitted (r(2) = 0.988) by a power-law relationship with a best-fit exponent, 0.598 +/- 0.028, coinciding closely with the 0.588 predicted for an excluded volume random coil. Therefore, it appears that the mean dimensions of the large majority of chemically denatured proteins are effectively indistinguishable from the mean dimensions of a random-coil ensemble.     

Irritable bowel syndrome: in search of an etiology: role of Blastocystis hominis

This study was designed to examine stool specimens of irritable bowel syndrome (IBS) patients for Blastocystis hominis, a common intestinal parasite. One hundred fifty patients were enrolled, 95 IBS cases and 55 controls. These patients provided a medical history, and underwent physical and laboratory evaluations that included stool microscopy and culture for B. hominis and colonoscopy. The 95 cases (51 males and 44 females) had a mean +/- SD age of 37.8 +/- 13.2 years. Stool microscopy was positive for B. hominis in 32% (30 of 95) of the cases and 7% (4 of 55) of the controls (P = 0.001). Stool culture was positive in 46% (44 of 95) of the cases and 7% (4 of 55) of the controls (P < 0.001). Stool culture for B. hominis in IBS was more sensitive than microscopy (P < 0.001). Blastocystis hominis was frequently demonstrated in the stool samples of IBS patients; however, its significance in IBS still needs to be investigated. Stool culture has a higher positive yield for B. hominis than stool microscopy.     

Phospholamban gene ablation improves calcium transients but not cardiac function in a heart failure model

Decreased amplitude and slower kinetics of cardiomyocyte intracellular calcium (Ca(i)(2+)) transients may underlie the diminished cardiac function observed in heart failure. These alterations occur in humans and animals with heart failure, including the TNF1.6 mouse model, in which heart failure arises from cardiac-specific overexpression of tumor necrosis factor alpha (TNF alpha). OBJECTIVE: Since ablation of phospholamban expression (PLBKO) removes inhibition of the sarcoplasmic reticulum (SR) Ca(2+) pump, enhances SR Ca(2+) uptake and increases contractility, we assessed whether ablation of phospholamban expression could improve cardiac function, limit remodeling, and improve survival in the TNF1.6 model of heart failure. METHODS: We bred PLBKO with TNF1.6 mice and characterized the progeny for survival, cardiac function (echocardiography), cardiac remodeling (hypertrophy, dilation, fibrosis), and Ca(2+)(i) transients and contractile function of isolated cardiomyocytes. RESULTS: PLB ablation did not improve survival, cardiac function, or limit cardiac chamber dilation and hypertrophy in TNF1.6 mice (TKO mice). However, contractile function and Ca(2+)(i) transients (amplitude and kinetics) of isolated TKO cardiomyocytes were markedly enhanced. This discordance between unimproved cardiac function, and enhanced Ca(2+)(i) cycling and cardiomyocyte contractile parameters may arise from a continued overexpression of collagen and decreased expression of gap junction proteins (connexin 43) in response to chronic TNF alpha stimulation. CONCLUSIONS: Enhancement of intrinsic cardiomyocyte Ca(2+)(i) cycling and contractile function may not be sufficient to overcome several parallel pathophysiologic processes present in the failing heart.     

Influence of maternal diabetes on serum leptinemic and insulinemic status of the offspring: A case study of selected patients in a tertiary care hospital in Bangladesh

IntroductionLeptin is now known to be an important hormone affecting intrauterine fetal growth. Since growth of fetus is also affected by the glycemic status of the mother. Serum leptin of infant is influenced by the maternal diabetic state. Investigation of cord blood leptin in babies of DM (Diabetes Mellitus) and GDM (Gestational Diabetes Mellitus) mothers (controlled blood glucose levels) may provide some indication about involvement of genetic factor in the development of leptin abnormalities in fetus.AimThe study was taken to investigate whether cord blood insulin, c-peptide and leptin levels correlate with birth weight in offspring of DM mother.MethodsBlood was drawn from umbilical cord of 30 babies from GDM mothers (GDM-babies), 45 babies from Type 2 DM Mothers (DM-babies), and 30 babies from ND (Nondiabetic) mothers (ND-babies) of term pregnancy. Weight, blood glucose, placenta, serum leptin and c-peptide of the babies were measured.ResultsBirth weight of GDM and DM babies were significantly higher compared to ND-babies. Glucose level in GDM babies was significantly higher than ND and DM babies. Leptin levels in GDM babies were significantly higher than that of ND and DM babies. Serum c-peptide in GDM babies was significantly higher than DM and ND babies. However, there was no significant difference in leptin–glucose ratio among the three groups. Irrespective of degree of hyperglycemia leptin is a major determinant of fetal growth.ConclusionsDM mother produces different insulinemic and leptinemic responses in the fetus indicating a possible genetic involvement.     

Positive troponin in diabetic ketoacidosis without evident acute coronary syndrome predicts adverse cardiac events

BACKGROUND: Elevated troponin I has been associated with increased mortality in critically ill patients without acute coronary syndrome (ACS). However, the prognostic significance of troponin elevation in patients with diabetic ketoacidosis (DKA) without evident ACS has not been studied. METHODS: Retrospective study of all patients admitted to a U.S. tertiary center between 01/98 and 12/00 with DKA and had troponin I level measured. Patients with evidence of ACS or who met the American College of Cardiology/European Society of Cardiology (ACC/ESC) definition for myocardial infarction were excluded. Baseline characteristics, cardiac evaluation and 2 year major adverse coronary event (MACE) rate were compared between patients with positive and negative troponin. RESULTS: Ninety-six patients fulfilled the inclusion criteria of this study, 26 had positive troponin. There were no differences in baseline characteristics between the two groups. After a 2 year follow-up, there was significantly increased mortality in patients with elevated troponin (50.0% versus 27.1%, hazard-ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.8, p = 0.02). Patients with elevated troponin also had significantly increased MACE rate at 2 years (50.0% versus 28.6%, HR 2.6, 95% CI 1.3-5.3, p = 0.007) driven primarily by mortality. Using Cox Proportional Hazard Analysis, elevated troponin was a predictor of increased MACE after adjusting for confounding variables. (Adjusted HR 2.3, 95% CI 1.1-4.6, p = 0.02) CONCLUSIONS: Elevated troponin I in diabetic patients admitted with DKA identifies a group at very high risk for future cardiac events and mortality. Whether cardiac risk stratification of these patients will improve long term outcome remains to be studied.     

A comparison of atenolol and nebivolol in isolated systolic hypertension

OBJECTIVES: Some beta-blockers are less effective in reducing central blood pressure than other antihypertensive drugs, which may explain the higher rate of events in subjects randomized to atenolol in recent trials. We hypothesized that nebivolol, a mixed beta-blocker/nitro-vasodilator, would be more effective than atenolol in reducing central blood pressure and augmentation index (AIx). The aim of the present study was to test this in a double-blind, randomized, cross-over study, in a cohort of subjects with isolated systolic hypertension. METHODS: Following a 2-week placebo run-in, 16 never-treated hypertensive subjects received atenolol (50 mg), nebivolol (5 mg) and placebo, each for 5 weeks, in a random order. Seated brachial blood pressure and heart rate were measured. Aortic blood pressure, AIx and pulse wave velocity (PWV) were assessed non-invasively. RESULTS: The placebo-corrected fall in brachial pressure was similar between nebivolol and atenolol, as was the reduction in PWV (mean change +/- SEM: -1.0 +/- 0.3 and -1.2 +/- 0.2 m/s; P = 0.2). However, there was less reduction in heart rate (-19 +/- 2 versus -23 +/- 2 beats/min; P < 0.01) and increase in AIx (+6 +/- 1 versus +10 +/- 1%; P = 0.04), following nebivolol. Aortic pulse pressure was significantly lower (50 +/- 2 versus 54 +/- 2 mmHg; P = 0.02) after nebivolol. N-terminal pro-B-type natriuretic peptide (proBNP) rose on both drugs (100 +/- 33 versus 75 +/- 80 pg/ml; P < 0.01 for both, NS for comparison). CONCLUSIONS: Nebivolol and atenolol have similar effects on brachial blood pressure and aortic stiffness. However, nebivolol reduces aortic pulse pressure more than atenolol, which may be related to a less pronounced rise in AIx and bradycardia. Whether this will translate into differences in clinical outcome requires further investigation.     

2007 annual research and education meeting of the Spondyloarthritis Research and Therapy Network (SPARTAN)

OBJECTIVE: The Spondyloarthritis Research and Therapy Network (SPARTAN; www.spartangroup.org) was founded in 2003 by a group of North American clinicians and researchers to promote research, education, and treatment of spondyloarthritis (SpA). In past years, it has produced and disseminated United States-specific modifications of the ASsessments in Ankylosing Spondylitis (ASAS) guidelines for the use of anti-tumor necrosis factor (TNF) therapy in AS1,2. SPARTAN held its fifth annual research meeting in September 2007 in Cleveland, Ohio. Highlights of the meeting included updates on current research in SpA, including epidemiology and genetics, bone formation and inflammation, biomarkers, activation of the IL-23/IL-17 axis, and animal models. A presentation was made on basic and clinical science of inflammatory bowel disease, and an educational pre-meeting conference was specifically designed for rheumatology fellows.     

Current status of oral and maxillofacial radiology in West Africa

Background

Oral and maxillofacial radiology became the ninth dental specialty recognized by the American Dental Association (ADA) in 1999. This came about following the discovery of X-rays by Wilhelm Conrad Roentgen in 1895 and, 14 days later, the application of X-rays to making dental radiographs by Otto Walkhoff. The purpose of this narrative study was to review the evolution of oral and maxillofacial radiology as a dental specialty in the USA and its recognition as a program of training by the West African College of Surgeons.

Methods

This study was conceptualized as a narrative review of the literature focusing on the history and development of oral and maxillofacial radiology in the USA. It builds a synthesis that describes the recognition of oral and maxillofacial radiology as a specialty of dentistry in West Africa, UK, Japan, and Australia.

Results

The main finding was that oral and maxillofacial radiology became the ninth specialty recognized by the American Dental Association, ADA, in October 13, 1999. On March 20, 2014, the West African College of Surgeons recognized this specialty and granted accreditation for postgraduate training. In the UK, Japan, and Australia, the postgraduate education in oral and maxillofacial radiology has two patterns, namely professional training and academic training.

Conclusions

The primary goal of the postgraduate training curriculum is to train radiologists who are competent to deliver care to patients in any clinical setting, including a dental school, hospital radiology practice, or private practice.

     

Assessing the validity of existing dental sealant quality measures

Background

Although sealants are highly effective in preventing caries in children, placement rates continue to be low. The authors’ goals were to implement and assess the performance of 2 existing sealant quality measures against a manual audit of charts at 4 dental institutions and to identify measurement gaps that may be filled by using data from electronic health records.

Mechanisms of oxidative stress-induced increase in salt sensitivity and development of hypertension in Sprague-Dawley rats

High salt intake produces vascular changes that contribute to the development of hypertension in salt-sensitive individuals. Because reactive oxygen species play a role in the pathogenesis of cardiovascular diseases, we investigated whether oxidative stress contributes to salt-sensitive hypertension. Sprague-Dawley rats were divided in different groups and received tap water (vehicle), 30 mmol/L of l-buthionine sulfoximine ([BSO] an oxidant), high salt ([HS] 1% NaCl), and BSO plus HS without and with antioxidant tempol (1 mmol/L) in drinking water for 12 days. Compared with vehicle, BSO treatment caused oxidative stress and mild increase in blood pressure. Thoracic aortic rings from BSO-treated rats exhibited decreased response to endothelium-independent vasorelaxants. In HS-treated rats, the response to vasoactive agents, as well as blood pressure, was unaffected. Concomitant treatment of rats with BSO and HS produced a marked increase in blood pressure and a decreased response to both endothelium-dependent and endothelium-independent vasorelaxants with an increase in EC(50). Incubation of aortic tissue from BSO-treated rats with sodium nitroprusside showed decreased cGMP accumulation, whereas HS rats had decreased basal NO synthase activity. Tempol decreased oxidative stress, normalized blood pressure, and restored NO signaling and responses to vasoactive compounds in BSO and BSO plus HS rats. We conclude that BSO increases oxidative stress and reduces NO signaling, whereas HS reduces NO levels by decreasing the NO synthase activity. These phenomena collectively result in reduced responsiveness to both endothelium -dependent and endothelium- independent vasorelaxants and may contribute to salt-sensitive hypertension.