Epidemiology and diagnosis of pulmonary embolism in lung cancer patients: is there a role for age adjusted D-dimers cutoff?

Journal of Thrombosis and Thrombolysis - Our knowledge about the incidence of pulmonary embolism (PE) and the performance of age adjusted D-dimers (Dd) cutoff amongst patients with lung cancer (LC)...     

<Emphasis Type="Italic">FTO</Emphasis> variant rs9939609 is associated with body mass index and waist circumference,but not with energy intake or physical activity in European- and African-American youth

Background  

Genome-wide association studies found common variants in the fat mass and obesity-associated (FTO) gene associated with adiposity in Caucasians and Asians but the association was not confirmed in African populations. Association of FTO variants with insulin resistance and energy intake showed inconsistent results in previous studies. This study aimed to assess the influence of FTO variant rs9939609 on adiposity, insulin resistance, energy intake and physical activity in European - (EA) and African-American (AA) youth.     

Oestrogen regulates proliferation, osteoblastic differentiation, collagen synthesis and periostin gene expression in human periodontal ligament cells through oestrogen receptor beta

Objective

The present study was designed to examine how oestrogen regulates proliferation, osteoblastic differentiation, collagen synthesis and periostin gene expression in primary human periodontal ligament (hPDL) cells.

Design

The short interfering RNA (siRNA) technique was used to inhibit oestrogen receptor beta (ERβ) expression hPDL cells. hPDL cell were isolated and fully characterized. A colorimetric assay was applied for the determination of alkaline phosphatase (ALP). An ELISA kit was used to detect osteocalcin (OCN) levels. Collagen synthesis was determined by measuring the incorporation of L-[3H] praline. RT-PCR was performed to detection of periostin mRNA relative gene expression.

Results

ERβ mRNA was expressed in hPDL cells and significant inhibition of mRNA expression and ERβ mature protein of the ERβ was evident in the siRNA group. At 72 h, there was a significant increase in non-transfected hPDL cell proliferation after estradiol stimulation. Addition of 17β-estradiol significantly enhanced ALP activity and production of OCN in non-transfected cells but had no effect on collagen synthesis. A clear increase in periostin mRNA expression levels was observed after incubating hPDL cells with estradiol. In hPDL-siERβ cells, the application of estradiol did not produce any evident differences in periostin mRNA expression

Conclusions

ERβ may play important roles in oestrogen-induced effects on hPDL cell proliferation, osteoblastic differentiation and expression of key molecules for the functional and structural integrity of the periodontium (i.e. periostin).     

Muscarinic stimulation of the rat isolated whole bladder: pathophysiological models of detrusor overactivity

1 Hypotheses as to the pathophysiological basis of bladder detrusor muscle overactivity (DO) have identified both central nervous and peripheral mechanisms as likely contributory factors. In this paper, we describe peripheral autonomous bladder activity in two animal models of DO and discuss how the differences observed between the two models support the likelihood that clinical DO has a multifactorial basis. 2 A total of 12 adult female Sprague-Dawley rats underwent obstruction or sham operation for 1 or 4 weeks. Six adult female spontaneously hypertensive rats (SHR) were compared with normal Wistar controls. Bladders were microsurgically removed and mounted in whole organ tissue baths. Recordings of intravesical pressure in response to the muscarinic receptor agonist arecaidine were performed under standardized conditions. 3 In the partially obstructed rat bladder, the amplitude of pressure fluctuations elicited by the muscarinic agonist arecaidine was significantly increased compared with sham-operated animals. The tonic component of the response was no different for the two groups. No difference from controls was apparent in the SHR. 4 We conclude that alterations in autonomous bladder activity in the obstructed rat model suggest that peripheral functional changes contribute to the pathophysiological abnormality. In contrast, the fundamental abnormality in the SHR appears to be at a more central level. The observations support the supposition that lesions at widely separate sites can give rise to apparently similar abnormalities of lower urinary tract function.     

Characteristics of potential living kidney donors in Ivory Coast: a survey prior to a project of kidney transplantation in French Black Africa

The source of living kidney donors in the general population remains underused. The present study aims at assessing the prevalence and the characteristics of potential living kidney donors in Ivory Coast in a view of a project of kidney transplantation in French Black Africa. A survey was undertaken in Abidjan from 30 June to 7 July 2006. Nine hundred (and) sixty-two subjects living in the capital and aged between 19 and 64 years old were randomly chosen using data from the 1998 population census. Subjects were asked their age, gender, nationality, marital status, information on kidney graft and renal failure, and their willingness to donate kidney to a relative or friend for transplantation purpose. Seventy per cent of the population study appeared favourable to kidney donation. Potentials living kidney donors have displayed following characteristics: age inferior to 26 years old [OR=2.08, P<0.02, 95%CI: 1.10-3.92]; Ivorians national [OR=2.72, P<0.002, 95% CI 1.42-5.21]; having heard of kidney transplantation (OR=1.89, P<0.047, 95% CI 1-3.54]); the death of a relative or friend from renal failure [OR=1.82, P<0.002, 95% CI 1.25 2.67]. Being married adversely affect kidney donation [OR=0.52, P<0.0002, 95% CI 0.34-0.79]. Potentials living kidney donors are in great number in Ivory Coast, who had specific characteristics.     

Developmental changes in adiposity in toddlers and preschoolers in the GENESIS study and associations with the ACE I/D polymorphism

OBJECTIVES: To investigate the relationship between the angiotensin I-converting enzyme 1 (ACE) I/D polymorphism and adiposity-related phenotypes in a large cohort of toddlers and preschoolers. METHODS: Body composition measurements and DNA samples were obtained from 2102 Greek children aged 1-6 years, as part of a large-scale epidemiological study (GENESIS). All children were genotyped for the ACE I/D polymorphism and gender- and age-stratified statistical analyses were performed. RESULTS: In girls aged 4-6 years, the D-allele was associated with higher measurements of body mass index (BMI) (P=0.018), waist (P=0.001) and upper arm (P=0.013) circumferences, genotype accounting for 2.5, 4 and 3% of the phenotypic variance, respectively. In boys, the D-allele showed strong associations with lower BMI (P=0.001) at the age of 1-2 years that explained 17% of the phenotypic variance and with larger suprailiac skinfold (P=0.008) at 3-4 years old that explained 2% of the variance. No other significant associations between the ACE I/D polymorphism and adiposity-related phenotypes were found. In girls, the age at which significant associations were revealed coincided with the age at which BMI was observed to increase after its developmental nadir, but this feature of the association was not observed in boys. CONCLUSIONS: The ACE I/D polymorphism is associated with developmental and physiological changes in adiposity-related traits during early childhood in a gender- and age-specific manner.     

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.     

Muscarinic stimulation of the mouse isolated whole bladder: physiological responses in young and ageing mice

1 Peripheral autonomous bladder activity is an incompletely understood property that may be important both in normal bladder function and in functional problems of the lower urinary tract. We describe how a muscarinic agonist, arecaidine, influences intravesical pressure and intramural bladder contractions in the isolated mouse and how response varies in ageing mice. 2 A group of 12 mice aged 3-4 months was compared with an 'ageing' group of 12 mice age 28-34 months. Bladders were microsurgically removed and mounted in whole organ tissue baths. The effects of the muscarinic agonist arecaidine on intravesical pressure and intramural contractions were performed at different bladder volumes. 3 In normal mice, arecaidine elicited tonic and phasic contractions, the latter showing a more substantial increase in amplitude with bladder distension. Localized 'micromotion' contractions were seen in the bladder wall, with regional differences arising after exposure to arecaidine. A background release of acetylcholine was inferred from the pressure increase induced by the cholinesterase inhibitor physostigmine. 4 Both micromotion activity and the phasic component of the arecaidine response were substantially reduced in ageing mice; the tonic component was preserved in the same specimens. 5 We conclude that the enhanced pressure fluctuations seen at high bladder volumes may act as a peripheral determinant of bladder capacity, and that changes in such activity may contribute to altered functional capacity and lower urinary tract symptoms in ageing individuals.     

Location of interstitial cells and neurotransmitters in the mouse bladder

INTRODUCTION: To investigate whether interstitial cells (ICs) are present in the adult mouse bladder, and what transmitters characterize adjacent nerve fibres, as ICs in human and guinea-pig bladder lie close to nerve fibres but transmitters present in these nerves have not yet been reported. MATERIALS AND METHODS: Sections of the bladder wall from 12 adult male mice (six each, aged 3-4 or 18-24 months) were incubated in carboxygenated Krebs' solution containing isobutyl-methyl-xanthene (1 mm), followed by the nitric oxide (NO) donor diethylamino-NONOate; control tissues remained in Krebs' solution. Samples were fixed in 4% paraformaldehyde and processed for immunofluorescence histochemistry for cGMP, neuronal NO synthase (nNOS), vesicular acetylcholine transferase (VAChT), calcitonin gene-related polypeptide (CGRP) and protein gene product (PGP) 9.5. ICs were identified as non-neuronal cells of appropriate morphology manifesting an increase in cGMP after exposure to the NO donor. RESULTS: ICs were apparent in the outer muscle, but not the inner muscle or suburothelial region. nNOS- and CGRP-immunoreactive fibres were close to and alongside IC processes. In contrast, nerve fibres containing VAChT were only occasionally found close to ICs and rarely running alongside them. ICs showed no immunoreactivity to c-kit. There was no overt difference in IC cell distribution between young and aged adult specimens. Older mice showed patchy denervation of the detrusor, but ICs were not specifically affected. CONCLUSIONS: ICs are confined to the outer part of the bladder wall in the mouse and may receive peptidergic and nitrergic innervation, which might serve to modulate their putative functional role. Alterations in the overall IC population do not appear to underlie ageing-related changes in lower urinary tract function.