Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin.

The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO2 nanomaterials and endothelial cells' adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as ß-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness.

Badminton injuries in youth competitive players.

AIM: The aim of the study was to examine sports injury pattern and establish cost of injuries in relation to training of 58 competitive badminton players in a Malaysian National Sports School. METHODS: This one-year prospective observational study recruited all the 13-16 year old students after obtaining informed consent from their appointed guardian. All participants were requested to report any injuries, which were pain or disabilities that occur within the study period (September 1, 2008 to August 31, 2009) either during training or competition. Injured students were to seek treatment from the researcher(s) who made weekly visits and they were then followed up accordingly until they return to full training. Details and progress of the injuries were documented during each visit. RESULTS: Sixty-three injuries were recorded. Soft tissue sprains/strains were the commonest injury (64%). About one third of the injuries occurred in the lower limb especially the knees and was followed by back injuries; 38% of the injuries did not require training modification, half of these injuries resumed training within one week. Upon full training, half of them were still symptomatic. Injury risk was 57%; injury rate was 0.9 injuries/ player/1000 training hours. CONCLUSION: Badminton injuries mostly involved the lower limb and almost all overuse injuries occurred in the lower limb. However, badminton injuries as a whole were predominantly sprains and strains, and not overuse in nature as widely believed.

Serum leptin levels in older patients with hip fracture--impact on peri-operative myocardial injury.

To evaluate whether there is a relationship between admission serum leptin concentrations and peri-operative myocardial injury, 238 consecutive older patients (mean age 81.9+/-7.9 years; 172 women) with low-trauma hip fracture were assessed. Myocardial injury as defined by elevated serum cardiac troponin I was associated with lower leptin levels analyzed as continuous or categorical variables. Patients with serum leptin concentrations <12ng/ml (medium value) had a two-fold greater increased risk for such complications compared with those with higher leptin levels (odd ratio 2.13, 95% confidence interval 1.06-4.28; p=0.033). This association remained significant after adjustments for age, gender, clinical (history of coronary artery disease [CAD], stroke, hypertension, diabetes, dementia), hematological (red, white, and lymphocyte count, hemoglobin, hematocrit), metabolic (parathyroid hormone [PTH], albumin), renal(creatinine, urea, glomerular filtration rate [GFR]), and inflammatory (C-reactive protein [CRP], ferritin) factors. The predictive value of lower leptin levels increased significantly when used in combination with traditional risk factors for myocardial injury.

Elevated serum cardiac troponin I in older patients with hip fracture: incidence and prognostic significance.

INTRODUCTION: Cardiovascular complications are the main causes of morbidity and mortality in patients with osteoporotic hip fracture (HF). The aim of this prospective study was to evaluate the incidence and prognostic significance of elevated cardiac troponin I (cTnI) in the early peri-operative period in older patients with HF. MATERIALS AND METHODS: A blind evaluation of myocardial injury as detected by cTnI elevation in 238 consecutive older patients with low-trauma HF (mean age 81.9 +/- 7.8 (SD) years; 72% females). Data on demographic and clinical characteristics, in-hospital mortality, hospital length of stay and discharge destination were collected prospectively. Serum cTnI level was analysed from blood collected routinely in the first 72 h of hospital admission. RESULTS: Sixty-nine (29%) patients had elevated cTnI (>0.06 microg/l) but myocardial injury was clinically recognised in only 23 (33%) and only 24 (34.8%) had a history of coronary artery disease (CAD). Patients with elevated cTnI were significantly older, more often had American Society of Anaesthesiologist status score >or=3, a history of CAD or stroke and more often were current smokers than the patients without cTnI elevation. In multivariate regression analysis only age was an independent predictor of cTnI elevation. Patients with cTnI release were twice as likely to have a length of stay >or=20 days (P = 0.047) and 2.7 times more likely to be discharged to a long-term residential care facility (RCF) (P = 0.013). cTnI level >or=1 microg/l was a strong independent predictor of all-cause mortality with 98.3% specificity and 89.1% negative predictive value. CONCLUSION: Peri-operative myocardial injury is common in older HF patients but is frequently unrecognised clinically. Elevated blood cTnI level is an independent predictor of prolonged length of hospital stay (>or=20 days), need for long-term RCF and mortality (if cTnI >or=1 microg/l).

Recurrent neural tube defects.

We report a case of recurrent neural tube defects in a 30-year-old multigravida with no medical or family history of note. She presented with a significant history of having three (out of four) previous pregnancies affected by neural tube defects diagnosed at the 20-week foetal anomaly ultrasonographical scans, and which resulted in mid-trimester pregnancy terminations. Previous investigations for the foetuses did not yield any obvious cause. We discuss the possible differential diagnoses and aetiological factors. Rare causes of neural tube defects need to be excluded in recurrent cases with no obvious aetiology.

Cysteine protease falcipain 1 in Plasmodium falciparum is biochemically distinct from its isozymes.

Falcipains form a class of papain-like cysteine proteases found in Plasmodium falciparum. This group of proteases has been suggested to be promising targets for anti-malarial chemotherapy. Despite being the first falcipain to be identified, the physiological role(s) of falcipain 1 (fp1) remains a mystery. Its suggested functions include haemoglobin degradation, erythrocytic invasion and oocyst production. In this study, the procurement of the gene coding for fp1 and its soluble expression in a heterologous host, Escherichia coli, have enabled further enzyme characterization. The recombinant fp1 protease was found to be unlike falcipain 2 (fp2A) in being more active at neutral pH than at acidic pH against the Z-LR-AMC fluorogenic substrate, suggesting a probable localization in the cytosol and not in the food vacuole. Interestingly, a common cysteine specific inhibitor, E64, did not inhibit fp1 activity, indicating dissimilar biochemical characteristics of fp1 from the other falcipains. This may be explained by computational analysis of the primary structures of the falcipain isozymes, as well as that of papain. The analysis revealed that Tyr61 (papain numbering), which is correspondingly absent in fp1, might be an important residue involved in E64 substrate binding.

Selective uptake of noradrenaline, dopa, and 5-hydroxytryptamine by the nervous system of Phocanema decipiens (Nematoda): a light autoradiographic and ultrastructural study.

As determined by light microscopic autoradiography, parts of the nervous system of Phocanema decipiens have selective and high affinity mechanisms for the uptake of tritiated noradrenaline, dihydroxyphenylalanine (dopa) and 5-hydroxytryptamine. In the nervous system, noradrenaline is accumulated only by the four papillary nerves and two fibers in the nerve ring. The precursor dopa is also taken up by these neurons and, in addition, by the lateral nerves. 5-Hydroxytryptamime is accumulated by the three pharyngeal nerves, two cells in each lateral ganglion, and two other fibers in the nerve ring. With adjacent ultrathin sections, the labelled papillary nerve and lateral ganglion were examined ultrastructurally and found to contain various dense core vesicles which are similar to those in other aminergic neurons. The adjoining unlabelled cells of the same neurons are found, on the other hand, to contain dense agranular vesicles. With these results, the noradrenaline accumulating neurons are suggested to be noradrenergic and to contain the amine synthesizing enzymes. The lateral nerves are regarded, for the present, as dopaminergic neurons. These suggestions are in agreement with the previous demonstration of catecholaminergic neurons in this nematode. The 5-hydroxytryptamine accumulating neurons are tentatively identified as tryptaminergic.