Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand fly Lutzomyia longipalpis blocks protease-activated receptor 2 activation and inhibits inflammation and thrombosis in vivo.

OBJECTIVE: Blood-sucking arthropods' salivary glands contain a remarkable diversity of antihemostatics. The aim of the present study was to identify the unique salivary anticoagulant of the sand fly Lutzomyia longipalpis, which remained elusive for decades. METHODS AND RESULTS: Several L. longipalpis salivary proteins were expressed in human embryonic kidney 293 cells and screened for inhibition of blood coagulation. A novel 32.4-kDa molecule, named Lufaxin, was identified as a slow, tight, noncompetitive, and reversible inhibitor of factor Xa (FXa). Notably, Lufaxin's primary sequence does not share similarity to any physiological or salivary inhibitors of coagulation reported to date. Lufaxin is specific for FXa and does not interact with FX, Dansyl-Glu-Gly-Arg-FXa, or 15 other enzymes. In addition, Lufaxin blocks prothrombinase and increases both prothrombin time and activated partial thromboplastin time. Surface plasmon resonance experiments revealed that FXa binds Lufaxin with an equilibrium constant ≈3 nM, and isothermal titration calorimetry determined a stoichiometry of 1:1. Lufaxin also prevents protease-activated receptor 2 activation by FXa in the MDA-MB-231 cell line and abrogates edema formation triggered by injection of FXa in the paw of mice. Moreover, Lufaxin prevents FeCl(3)-induced carotid artery thrombus formation and prolongs activated partial thromboplastin time ex vivo, implying that it works as an anticoagulant in vivo. Finally, salivary gland of sand flies was found to inhibit FXa and to interact with the enzyme. CONCLUSIONS: Lufaxin belongs to a novel family of slow-tight FXa inhibitors, which display antithrombotic and anti-inflammatory activities. It is a useful tool to understand FXa structural features and its role in prohemostatic and proinflammatory events.

Evaluación del uso de exosomas como aloantígenos para la inducción de tolerancia en trasplante

La consecución de tolerancia aloespecífica es de mucha relevancia en trasplante. Las células dendríticas (DC) son las principales responsables de la inducción de la respuesta inmune frente a las moléculas de histocompatibilidad (MHC) del donante, provocando el rechazo del injerto. Sin embargo las DC son también responsables de la inducción de tolerancia. Diversos modelos animales de alotrasplante han mostrado la tolerización del injerto mediante DC diferenciadas in vitro en condiciones tolerogénicas (tDC). En humanos, las fuentes de aloantígenos potencialmente utilizables en terapia son, entre otras, los cuerpos apoptóticos y los exosomas. Éstos expresan antígenos MHC de forma abundante y su composición es relativamente uniforme, lo que supone una ventaja frente a otras fuentes. En este proyecto, se ha evaluado la obtención de exosomas secretados por una línea de linfocitos T y por células dendríticas derivadas de médula ósea. Se ha caracterizado la captura de exosomas derivados de linfocitos T por células dendríticas humanas derivadas de sangre periférica y su presentación a linfocitos T autólogos. Por otra parte, se ha comenzado a desarrollar los experimentos para estudiar la inducción de tolerancia en un modelo de trasplante renal en rata. Se han generado células dendríticas tolerógenicas derivadas de médula ósea (tolDC), en presencia de dexametasona. Las tolDC expresan menos moléculas de histocompatibilidad y de coestimulación e inducen una menor proliferación en reacciones mixtas leucocitaras, comparadas con las células dendríticas maduras. Por último, se han caracterizado los exosomas de plasma humano con el fin de estudiar su posible uso como aloantígenos. El análisis proteómico revela la presencia de proteínas relacionadas con el sistema inmune, la coagulación, la señalización celular y moléculas implicadas en el transporte y metabolismo de nutrientes. El estudio de la captura por diferentes líneas celulares sugiere que deben existir mecanismos específicos para su internalización.

A New Method for Fixing Biomphalaria glabrata for Histologic Studies, Using Shell Perforation

A new technique for fixation of Biomphalaria glabrata for histologic studies is described. It consists in performing several external holes in the shell, before placing the entire snail into the fixative. It is a very practical and quick procedure that showed excellent results when compared to the usual techniques.

Health in Ireland, Key Trends 2007

This booklet provides an overview of selected key trends in health in Ireland in recent years. Tables and graphs are presented which summarise information on demographics, on health status and on health care in order to give a quick reference guide in major areas of health and health services. The past decade has been a time of rapid change in many aspects of life in Ireland. The evidence presented in this booklet reflects this period of change with respect to health. Download document here

Ultrasound monitoring of structural urinary tract disease in Schistosoma haematobium infection

A major advance in our understanding of the natural history of Schistosoma haematobium-related morbidity has come through the introduction of the portable ultrasound machines for non-invasive examination of the kidneys and bladder. With the use of generators or battery packs to supply power in non-clinical field settings, and with the use of instant photography or miniaturized thermal printers to record permanent images, it is possible to examine scores of individuals in endemic communities every day. Broad-based ultrasound screening has allowed better definition of age-specific disease risks in urinary schistosomiasis. Results indicate that urinary tract abnormalities are common (18% overall prevalence) in S. haematobium transmission areas, with a 2-4% risk of either severe bladder abnormality or advanced ureteral obstruction. In longitudinal surveys, ultrasound studies have shown that praziquantel and metrifonate therapy are rapidly effective in reversing urinary tract abnormalities among children. The benefits of treating adults are less well known, but research in progress should help to define this issue. Similarly, the prognosis of specific ultrasound findings needs to be clarified, and the ease of sonographic examination will make such long-term follow-up studies feasible. In summary, the painless, quick, and reproducible ultrasound examination has become an essential tool in the study of urinary schistosomiasis.

Detection of telomerase activity in Plasmodium falciparum using a nonradioactive method

A simple, quick and sensitive method was used to detect telomerase activity in Plasmodium falciparum. The telomeric repeat amplification protocol (TRAP assay) was modified using electrophoresis and staining with SYBR-green I to detect telomerase activity in a range of 10² to 10(7) parasites. This might be a useful way to ascertain telomerase activity in different types of nontumor cells.

Safe hands

We all know the dangers of dirty hands when it comes to food preparation, but did you know that a quick rinse under the tap doesn’t actually get rid of dangerous germs? Most people don’t dry their hands either, but leaving hands damp actually helps germs to breed in the moisture, and allows them to spread more easily onto whatever you touch next. So before handling food, don’t just splash ‘n’ dash - wash your hands thoroughly.

Mechanical properties of rat cardiac skinned fibers are altered by chronic growth hormone hypersecretion.

Chronic growth hormone (GH) hypersecretion in rats leads to increased isometric force without affecting the unloaded shortening velocity of isolated cardiac papillary muscles, despite a marked isomyosin shift toward V3. To determine if alterations occurred at the level of the contractile proteins in rats bearing a GH-secreting tumor (GH rats), we examined the mechanical properties of skinned fibers to eliminate the early steps of the excitation-contraction coupling mechanism. We found that maximal active tension and stiffness at saturating calcium concentrations (pCa 4.5) were markedly higher in GH rats than in control rats (tension, 52.9 +/- 5.2 versus 38.1 +/- 4.6 mN.mm-2, p < 0.05; stiffness, 1,105 +/- 120 versus 685 +/- 88 mN.mm-2.microns-1, p < 0.01), whereas values at low calcium concentrations (pCa 9) were unchanged. In addition, the calcium sensitivity of the contractile proteins was slightly but significantly higher in GH rats than in control rats (delta pCa 0.04, p < 0.001). The crossbridge cycling rate, reflected by the response to quick length changes, was lower in GH rats than in control rats (62.0 +/- 2.6 versus 77.4 +/- 6.6 sec-1, p < 0.05), in good agreement with a decrease in the proportion of alpha-myosin heavy chains in the corresponding papillary muscles (45.5 +/- 2.0% versus 94.6 +/- 2.4%, p < 0.001). The changes in myosin heavy chain protein phenotype were paralleled by similar changes of the corresponding mRNAs, indicating that the latter occurred mainly at a pretranslational level. These results demonstrate that during chronic GH hypersecretion in rats, alterations at the myofibrillar level contribute to the increase in myocardial contractility observed in intact muscle.

Standard Evaluation Framework for Weight Management Interventions - Core Criteria

The National Obesity Observatory was established to provide a single point of contact for wide-ranging authoritative information on data and evidence related to obesity, overweight, underweight and their determinants. The Standard Evaluation Framework is a list of data collection criteria and supporting guidance for collecting high quality information to support the evaluation of weight management interventions. This is a quick reference guide to the core criteria of the Standard Evaluation Framework. Essential criteria are presented as the minimum recommended data for evaluating a weight management intervention. Desirable criteria are additional data that would enhance the evaluation.refer to the resource

Briefing 25: NCMP data 2008/9, East of England: Body Mass Index (BMI) thresholds

One in a series of six data briefings based on regional-level analysis of data from the National Child Measurement Programme (NCMP) undertaken by the National Obesity Observatory (NOO). The briefings are intended to complement the headline results for the region published in January 2010, at Quick Link 20510.

Briefing 26: NCMP data 2008/9, East of England: Ethnicity

One in a series of six data briefings based on regional-level analysis of data from the National Child Measurement Programme (NCMP) undertaken by the National Obesity Observatory (NOO). The briefings are intended to complement the headline results for the region published in January 2010, at Quick Link 20510.

Briefing 27: NCMP data 2008/9, East of England: Deprivation

One in a series of six data briefings based on regional-level analysis of data from the National Child Measurement Programme (NCMP) undertaken by the National Obesity Observatory (NOO). The briefings are intended to complement the headline results for the region published in January 2010, at Quick Link 20510.

Briefing 28: NCMP data 2008/9, East of England: Gender

One in a series of six data briefings based on regional-level analysis of data from the National Child Measurement Programme (NCMP) undertaken by the National Obesity Observatory (NOO). The briefings are intended to complement the headline results for the region published in January 2010, at Quick Link 20510.

Briefing 29: NCMP data 2008/9, East of England: ONS SOA classification

One in a series of six data briefings based on regional-level analysis of data from the National Child Measurement Programme (NCMP) undertaken by the National Obesity Observatory (NOO). The briefings are intended to complement the headline results for the region published in January 2010, at Quick Link 20510.

Web taller de servei ràpid :Desenvolupament d'una aplicació web amb tecnologies J2EE

El projecte és una web per a un taller mecànic dels anomenats ¿de servei ràpid¿, amb tecnologies J2EE.Els clients del taller poden demanar dia i hora per fer unareparació al seu cotxe. I el taller, en el seu cas el cap de taller o persona autoritzada, pot llistar les reparacions del dia.