Nasal potential difference to detect Na+ channel dysfunction in acute lung injury

Pulmonary fluid clearance is regulated by the active transport of Na+ and Cl- through respiratory epithelial ion channels. Ion channel dysfunction contributes to the pathogenesis of various pulmonary fluid disorders including high-altitude pulmonary edema (HAPE) and neonatal respiratory distress syndrome (RDS). Nasal potential difference (NPD) measurement allows an in vivo investigation of the functionality of these channels. This technique has been used for the diagnosis of cystic fibrosis, the archetypal respiratory ion channel disorder, for over a quarter of a century. NPD measurements in HAPE and RDS suggest constitutive and acquired dysfunction of respiratory epithelial Na+ channels. Acute lung injury (ALI) is characterized by pulmonary edema due to alveolar epithelial-interstitial-endothelial injury. NPD measurement may enable identification of critically ill ALI patients with a susceptible phenotype of dysfunctional respiratory Na+ channels and allow targeted therapy toward Na+ channel function. text of link

Decreased respiratory system compliance on the sixth day of mechanical ventilation is a predictor of death in patients with established acute lung injury

Background: Multiple studies have identified single variables or composite scores that help risk stratify patients at the time of acute lung injury (ALI) diagnosis. However, few studies have addressed the important question of how changes in pulmonary physiologic variables might predict mortality in patients during the subacute or chronic phases of ALI. We studied pulmonary physiologic variables, including respiratory system compliance, P/F ratio and oxygenation index, in a cohort of patients with ALI who survived more than 6 days of mechanical ventilation to see if changes in these variables were predictive of death and whether they are informative about the pathophysiology of subacute ALI.

Altered distribution of interstitial cells and innervation in the rat urinary bladder following spinal cord injury

Introduction Changes in the distribution of interstitial cells (IC) are reportedly associated with dysfunctional bladder. The present study investigated whether spinal cord injury (SCI) resulted in changes to IC subpopulations (vimentin-positive with the ultrastructural profile of IC), smooth muscle and nerves within the bladder wall and correlated cellular remodelling with functional properties. Methods Bladders from SCI (T8/9 transection) and sham-operated rats five-weeks post-injury were used for ex vivo pressure-volume experiments or processed for morphological analysis with transmission electron microscopy (TEM) and light/confocal microscopy. Results Pressure-volume relationships revealed low-pressure, hypercompliance in SCI bladders indicative of decompensation. Extensive networks of vimentin-positive IC were typical in sham lamina propria and detrusor but were markedly reduced post-SCI; semi-quantitative analysis showed significant reduction. Nerves labelled with anti-neurofilament and anti-vAChT were notably decreased post-SCI. TEM revealed lamina propria IC and detrusor IC which formed close synaptic-like contacts with vesicle-containing nerve varicosities in shams. Lamina propria and detrusor IC were ultrastructurally damaged post-SCI with retracted/lost cell processes and were adjacent to areas of cellular debris and neuronal degradation. Smooth muscle hypertrophy was common to SCI tissues. Conclusions IC populations in bladder wall were decreased five weeks post-SCI, accompanied with reduced innervation, smooth muscle hypertrophy and increased compliance. These novel findings indicate that bladder wall remodelling post-SCI affects the integrity of interactions between smooth muscle, nerves and IC, with compromised IC populations. Correlation between IC reduction and a hypercompliant phenotype suggests that disruption to bladder IC contribute to pathophysiological processes underpinning the dysfunctional SCI bladder.

AM1- receptor dependent protection by intermedin of human vascular and cardiac non-vascular cells from ischaemia-reperfusion injury

Intermedin (IMD) protects rodent heart and vasculature from oxidative stress and ischaemia. Less is known about distribution of IMD and its receptors and the potential for similar protection in man. Expression of IMD and receptor components were studied in human aortic endothelium cells (HAECs), smooth muscle cells (HASMCs), cardiac microvascular endothelium cells (HMVECs) and fibroblasts (v-HCFs). Receptor subtype involvement in protection by IMD against injury by hydrogen peroxide (H2O2, 1 mmol l?¹) and simulated ischaemia and reperfusion were investigated using receptor component-specific siRNAs. IMD and CRLR, RAMP1, RAMP2 and RAMP3 were expressed in all cell types.When cells were treated with 1 nmol l?¹ IMD during exposure to 1 mmol l?¹ H2O2 for 4 h, viability was greater vs. H2O2 alone (P<0.05 for all cell types). Viabilities under 6 h simulated ischaemia differed (P<0.05) in the absence and presence of 1 nmol l?¹ IMD: HAECs 63% and 85%; HMVECs 51% and 68%; v-HCFs 42% and 96%. IMD 1 nmol l?¹ present throughout ischaemia (3 h) and reperfusion (1 h) attenuated injury (P<0.05): viabilities were 95%, 74% and 82% for HAECs, HMVECs and v-HCFs, respectively, relative to those in the absence of IMD (62%, 35%, 32%, respectively). When IMD 1 nmol l?¹ was present during reperfusion only, protection was still evident (P<0.05, 79%, 55%, 48%, respectively). Cytoskeletal disruption and protein carbonyl formation followed similar patterns. Pre-treatment (4 days) of HAECs with CRLR or RAMP2, but not RAMP1 or RAMP3, siRNAs abolished protection by IMD (1 nmol l?¹) against ischaemia-reperfusion injury. IMD protects human vascular and cardiac non-vascular cells from oxidative stress and ischaemia-reperfusion,predominantly via AM1 receptors.

Epidemiology of Adolescent Rugby Injuries: A Systematic Review

OBJECTIVE: Despite recent increases in the volume of research in professional rugby union, there is little consensus on the epidemiology of injury in adolescent players. We undertook a systematic review to determine the incidence, severity, and nature of injury in adolescent rugby union players.

DATA SOURCES: In April 2009, we performed a computerized literature search on PubMed, Embase, and Cochrane Controlled Trials Register (via Ovid). Population-specific and patient-specific search terms were combined in the form of MEDLINE subject headings and key words (wound$ and injur$, rugby, adolescent$). These were supplemented with related-citation searches on PubMed and bibliographic tracking of primary and review articles.

STUDY SELECTION: Prospective epidemiologic studies in adolescent rugby union players.

DATA SYNTHESIS: A total of 15 studies were included, and the data were analyzed descriptively. Two independent reviewers extracted key study characteristics regarding the incidence, severity, and nature of injuries and the methodologic design.

CONCLUSIONS: Wide variations existed in the injury definitions and data collection procedures. The incidence of injury necessitating medical attention varied with the definition, from 27.5 to 129.8 injuries per 1000 match hours. The incidence of time-loss injury (>7 days) ranged from 0.96 to 1.6 per 1000 playing hours and from 11.4/1000 match hours (>1 day) to 12-22/1000 match hours (missed games). The highest incidence of concussion was 3.3/1000 playing hours. No catastrophic injuries were reported. The head and neck, upper limb, and lower limb were all common sites of injury, and trends were noted toward greater time loss due to upper limb fractures or dislocations and knee ligament injuries. Increasing age, the early part of the playing season, and the tackle situation were most closely associated with injury. Future injury-surveillance studies in rugby union must follow consensus guidelines to facilitate interstudy comparisons and provide further clarification as to where injury-prevention strategies should be focused.

The effect of increasing dietary fibre and the provision of straw racks on the welfare of sows housed in small static groups

This study assessed the effects of increasing dietary fibre levels in concentrate rations and providing access to straw in racks on the welfare of pregnant sows housed in small static groups. In a 2 x 2 factorial design experiment, 128 Large White x Landrace pregnant sows were offered one of two diets: (i) High fibre diet with 9% crude fibre, or (ii) Control diet with 4.5% CF, and one of two levels of access to a foraging substrate: (i) access to straw in racks or (ii) no straw. The study was replicated eight times using groups of four sows, and treatment periods lasted four weeks. Sows were housed in pens with voluntary cubicles and a slatted exercise area and were offered a wet diet twice a day. Back-fat levels were measured before sows were mixed into groups at 28 days post partum, and four weeks later. Aggressive interactions were recorded on the day of mixing, and injury scores were recorded one week post mixing. Scan sampling was used to collect data on general activity, posture and location of the sows, and on sham-chewing and bar-biting behaviours across the treatment period. In addition, detailed focal observations were carried out on all sows across the treatment period. Straw usage was also recorded. There were no treatment effects on changes in back-fat levels over the treatment period. Treatments had no effect on post-mixing aggression or on injury scores. However, focal observations showed that sows with access to straw were involved in fewer bouts of head-thrusting over the treatment period. Control diet sows spent more time inactive than sows on the high fibre diet, however high fibre diet sows spent more time lying with eyes closed than sows on the control diet. Sows on the high fibre diet with access to straw showed less sham-chewing and bar-biting behaviour than sows in other treatments. These results show that although a diet containing 9% crude fibre promoted resting behaviour, it was necessary to combine it with access to straw to reduce stereotypic behaviour of sows in small static groups.