Case Report: An unusual case of a transposition of the great arteries with a double aortic arch: a highly complex fetal diagnosis with an unpredictable outcome.

Published data estimate the prevalence of the vascular ring at approximately 7 per 10,000 live births. The association of a double aortic arch with a D-transposition of the great arteries has been rarely described in the literature. In this study, we report the prenatal diagnosis of a 28-year-old woman. A fetal echocardiography at a gestational age of 24 weeks + 6 days showed a D-transposition of the great arteries and a double aortic arch with a ventricular septal defect and pulmonary stenosis. On the first night after birth, the baby experienced an increase in lactate levels, with the rate of oxygen saturation consistently below 80%. A few hours after birth, the patient underwent a Rashkind procedure. An echocardiography, CT chest x-ray, and CT angiogram confirmed a diagnosis with a severe reduction of the tracheal lumen (>85%) and bronchomalacia. Then, the patient underwent posterior tracheopexy and aortopexy and later an arterial switch operation, ventricular septal defect closure, and resection of a part of the infundibular septum, accepting the risk of potential neoaortic obstruction. The literature has reported only two cases of patients with a fetal echocardiogram diagnosis. Therefore, our patient is only the third one with a fetal diagnosis and the second one with a complex intracardiac anatomy, characterized not only by a ventricular septal defect but also by two separate components of the obstruction (a bicuspid valve and a dysplastic valve with a posterior deviation of the infundibular septum). In conclusion, a D-transposition of the great arteries with a double aortic arch remains an extremely unusual association. The clinical outcome of these patients presents a high degree of variability and is entirely unpredictable in prenatal life. Our greatest aim as fetal and perinatal cardiologists is to improve the management and outcome of these patients through a fetal diagnosis, recognizing types of congenital heart disease in newborns who require early neonatal invasive procedures.

RadioLab project: knowledge of radon gas in Italy.

RadioLab is an Italian project, addressed to school-age people, and designed for the dissemination of scientific culture on the theme of environmental radioactivity, with particular regards to the importance of knowledge of radon gas exposure. The project is a nationwide initiative promoted by the National Institute of Nuclear Physics- INFN. First tool used by the project, and of immediate impact to assess the public awareness on radon, is the administration of the survey "do you know the radon gas?". In the survey, together with the knowledge of radon and of its sources, information on personal, cultural and territorial details regarding the interviewees are also taken. Reasonably, the survey invests not only young people, but also their relatives, school workers and, gradually, the public. The survey is administrated during exhibitions or outreach events devoted to schools, but also open to the public. The survey is in dual form: printed and online. The online mode clearly leads RadioLab project even outside the school environment. Based on the results of the survey, several statistical analyses have been performed and many conclusions are drawn about the knowledge of the population on the radon risk. The RadioLab benefit and the requirement to carry on the project goals, spreading awareness of environmental radioactivity from radon, emerge. The dataset involves all twenty Italian regions and consists of 28,612 entries covering the 5-year period 2018-2022.

Consecutive episodes of heart and kidney failure in an "otherwise" healthy young man.

BACKGROUND: Acute renal failure is a rare occurrence in a patient with an unremarkable past medical history and should always lead to an in depth clinical study. The occurrence in the same healthy young subject, of consecutive episodes of heart failure and of acute renal failure is an even rarer event and should prompt diagnostic tests and restrict the diagnostic hypotheses. CASE PRESENTATION: We present the case of a 28 year-old man who, while waiting to undergo assessment for a mild chronic kidney disease, was diagnosed with decompensated dilated cardiomyopathy and placed on diuretics and ß-blockers. After few weeks he developed a non oligoanuric acute renal failure with a slight elevation of serum calcium. Renal biopsy proved suggestive for renal sarcoidosis; thus the hypothesis of systemic sarcoidosis with cardiac and renal involvement was possible avoiding further delay in initiation of therapy. CONCLUSIONS: Cardiac sarcoidosis is usually silent but the majority of cases are diagnosed when cardiac symptoms are present in a patient with systemic sarcoidosis. Renal involvement with granulomatous interstitial nephritis is also quite rare and can be an unexpected finding at kidney biopsy. This case highlights the need to evaluate thoroughly clinical problems that do not fit in a specific scenario and emphasizes the importance of performing a kidney biopsy in case of kidney failure of unknown etiology.

Genetic analysis of human and swine influenza A viruses isolated in Northern Italy during 2010-2015.

Influenza A virus (IAV) infection in swine plays an important role in the ecology of influenza viruses. The emergence of new IAVs comes through different mechanisms, with the genetic reassortment of genes between influenza viruses, also originating from different species, being common. We performed a genetic analysis on 179 IAV isolates from humans (n. 75) and pigs (n. 104) collected in Northern Italy between 2010 and 2015, to monitor the genetic exchange between human and swine IAVs. No cases of human infection with swine strains were noticed, but direct infections of swine with H1N1pdm09 strains were detected. Moreover, we pointed out a continuous circulation of H1N1pdm09 strains in swine populations evidenced by the introduction of internal genes of this subtype. These events contribute to generating new viral variants-possibly endowed with pandemic potential-and emphasize the importance of continuous surveillance at both animal and human level.

Reduced fibrinolytic resistance in patients with factor XI deficiency. Evidence of a thrombin-independent impairment of the thrombin-activatable fibrinolysis inhibitor pathway.

UNLABELLED: Essentials Plasma of factor XI-deficient patients (FXI-dp) displays enhanced fibrinolysis. We investigated the role of thrombin activatable fibrinolysis inhibitor (TAFI) in 18 FXI-dp. FXI-dp generated less activated TAFI (TAFIa) on clotting challenge and were resistant to TAFIa. TAFI activation and TAFIa resistance correlated with bleeding score and bleeding phenotype. SUMMARY: Background Factor XI (FXI) deficiency, a rare disorder with unpredictable bleeding, has been associated with reduced fibrinolytic resistance as a result of abnormal fibrin density. Objective We investigated the involvement of thrombin-activatable fibrinolysis inhibitor (TAFI) in the increased lysability of FXI-deficient (FXI-def) clots and the role of thrombin. Patients/Methods Eighteen patients with FXI deficiency (1-58%) and 17 matched controls were investigated for fibrinolytic resistance to t-PA, thrombin generation, TAFI activation and response to TAFIa. Results When clotting was induced by 0.5 pm tissue factor (TF), FXI-def plasmas displayed less thrombin and TAFIa generation and shorter lysis time than controls. A 100-fold higher TF concentration (to bypass FXI) abolished the difference in thrombin generation but not in lysis time between patients and controls. Normalization of FXI levels by a FXI concentrate increased thrombin generation but had no effect on the lysis time of FXI-def plasma. Moreover, when clots were induced by purified thrombin and high concentrations of FXa inhibitor, FXI-def plasma still generated less TAFIa and displayed a shorter lysis time than controls. Finally, upon TAFIa addition, the lysis time of FXI-def plasma was prolonged significantly less than that of control plasma, suggesting a TAFIa resistance. TAFIa generation and TAFIa resistance were correlated with the bleeding score, displaying a considerable capacity to discriminate between patients with and without bleeding. Conclusions TAFI pathway impairment, largely caused by a hitherto unknown TAFIa resistance, appears to be one main cause of decreased fibrinolytic resistance in FXI deficiency and might be clinically useful for assessing the bleeding risk of FXI-def patients.

[Improving vaccination social marketing by monitoring the web]. / Migliorare il marketing sociale in tema di vaccinazioni "presidiando" il Web.

Immunisation is one of the most important and cost- effective interventions in Public Health because of their significant positive impact on population health.However, since Jenner's discovery there always been a lively debate between supporters and opponents of vaccination; Today the antivaccination movement spreads its message mostly on the web, disseminating inaccurate data through blogs and forums, increasing vaccine rejection.In this context, the Società Italiana di Igiene (SItI) created a web project in order to fight the misinformation on the web regarding vaccinations, through a series of information tools, including scientific articles, educational information, video and multimedia presentations The web portal (http://www.vaccinarsi.org) was published in May 2013 and now is already available over one hundred web pages related to vaccinations Recently a Forum, a periodic newsletter and a Twitter page have been created. There has been an average of 10,000 hits per month. Currently our users are mostly healthcare professionals. The visibility of the site is very good and it currently ranks first in the Google's search engine, taping the word "vaccinarsi" The results of the first four months of activity are extremely encouraging and show the importance of this project; furthermore the application for quality certification by independent international Organizations has been submitted.

Monoclonal antibodies targeting the antifibrinolytic activity of activated thrombin-activatable fibrinolysis inhibitor but not the anti-inflammatory activity on osteopontin and C5a.

BACKGROUND: Recently, anti-thrombin-activatable fibrinolysis inhibitor (TAFI) mAbs selectively inhibiting plasmin-mediated TAFI activation were shown to stimulate fibrinolysis in vitro and in vivo, suggesting, in contrast to other findings, that plasmin-mediated TAFI activation plays an important role in fibrinolysis regulation. OBJECTIVE: To further characterize the effects of two plasmin-specific anti-TAFI mAbs (MA-TCK11A9 and MA-TCK26D6) on TAFI-dependent inhibition of fibrinolysis. METHODS AND RESULTS: Both mAbs inhibited plasmin-mediated but not thrombin/thrombomodulin-mediated TAFI activation, whereas neither inhibited the cleavage of hippuryl-arginine by activated TAFI (TAFIa). They stimulated tissue-type plasminogen activator-induced fibrinolysis in different clot lysis models through a TAFI-dependent mechanism, especially in the presence of thrombomodulin (TM), a condition in which TAFI is largely activated by the thrombin-TM complex. In a fibrinolysis-based TAFIa activity assay, both mAbs inhibited TAFIa, whereas other mAbs targeting thrombin-TM-mediated TAFI activation did not. The inhibition of TAFIa activity, however, was substrate-specific, because neither mAb inhibited the cleavage of thrombin-activated osteopontin and C5a by TAFIa, thus sparing the anti-inflammatory activity of TAFIa. CONCLUSIONS: Our anti-TAFI mAbs, by selectively inhibiting TAFIa activity on fibrin, may represent the prototype of a new class of TAFI inhibitors with improved pharmacologic activity.

Immunity status against poliomyelitis in childbearing women in a province of northern Italy. A cross-sectional analysis.

This cross-sectional seroprevalence study was carried out in 2007 to estimate the immunological status associated with poliomyelitis among fertile women , according to demographic changes. We consecutively enrolled 493 healthy mothers at the time of delivery in order to assess immunity against poliomyelitis by a neutralisation inhibition test. Despite the lack of seronegative subjects, our investigation showed low GMTs, which confirmed a reduction in the "booster effect". The GMTs against poliovirus 1, poliovirus 2 and poliovirus 3 were 25.20, 14.79 and 8.80, respectively. The data that emerged from our survey showed that GMTs have decreased significantly since 1983 and reached low-to-medium values over the past 25 years. The serum prevalence studies, together with the vaccination coverage estimates, are useful and are strongly recommended in order to highlight and identify the possible scenarios in which susceptible subject groups may be present simultaneously as well the possibility of the reintroduction of wild virus in an area that was previously free of polio.

High hydrostatic pressure activity on the disinfection of clams artificially contaminated with feline calicivirus.

BACKGROUND: The contamination of shellfish with gastroenteric viruses may cause outbreaks because they are often eaten raw or under-cooked. High-hydrostatic pressure treatments have already proven to be effective in reducing high viral load in shellfish samples. The objectives are the assessment of the viral load reduction of contaminated clams using HHP treatments at different pressures and times and the study of the changes caused by these treatments in some food physical parameters. METHODS: Clams were contaminated with a solution containing Feline Calicivirus; they were closed in envelopes and treated with 300, 400, 500, 600 MPa for 1, 3, 5, 7 min for every pressure value. After the treatment the residual viral titre was calculated. The texture parameters were obtained after treating clams samples at the same pressure values but only for 3 and 7 min and analysing them with a TPA test. RESULTS: HHP treatments of 500 and 600 MPa were sufficient to cause a total inactivation at every timelength considered while with 300 and 400 MPa after 1 min, concentrations of 1.13 and 0.55 respectively were found. In general hardness and gumminess tend to increase after the treatment whereas springiness and cohesiveness decrease a bit. CONCLUSIONS: HHP treatments showed good sterilization ability against FCV but it's necessary to consider that FCV has a lower resistance to disinfection than Human norovirus. Texture changes are in line with what is reported in literature.

Swimming pools and health-related behaviours: results of an Italian multicentre study on showering habits among pool users.

OBJECTIVES: Showering before entering a swimming pool is highly recommended to reduce the risk of biological and chemical contamination. This study evaluated the behaviour of indoor swimming pool users; analysed the variables associated with lack of showering; and assessed awareness of the importance of showering. STUDY DESIGN: Cross-sectional study. METHODS: A self-administered questionnaire was used to collect data about users of swimming pools located in five different Italian cities. The association between specific variables and the lack of showering was assessed. P < 0.05 was considered to indicate statistical significance. RESULTS: In total, 4356 questionnaires were analysed. Sixty-five percent of interviewees always showered before entering the pool. The main reason given for pre-swim showering was 'to wash oneself' (50.5%); or 'to get used to the temperature of the water' (44.3%); and 5.2% answered 'for both reasons'. Risk factors significantly associated with lack of showering were: female sex (odds ratio (OR) 1.37, 95% confidence interval (CI) 1.2-1.59), age 14-17 years (OR 5.09, 95% CI 3.40-7.64); not reading the swimming pool rules (OR 1.24, 95% CI 1.10-1.41); living in Central Italy (OR 3.3, 95% CI 2.65-4.1) or Southern Italy (OR 1.35, 95% CI 1.18-1.55); and previous/current attendance of a swimming course (OR 1.7, 95% CI 1.48-1.97). CONCLUSIONS: The results revealed low compliance with the rule of showering before entering a swimming pool, and little awareness of the preventive role of showering in the hygienic management of swimming pools. There is a need for targeted educational interventions to inform swimming pool users of the reasons for the importance of showering before entering a pool.

Effect of warfarin treatment on thrombin activatable fibrinolysis inhibitor (TAFI) activation and TAFI-mediated inhibition of fibrinolysis.

BACKGROUND: Severe clotting deficiencies are associated with enhanced in vitro fibrinolysis due to insufficient thrombin activatable fibrinolysis inhibitor (TAFI) activation. Because oral anticoagulant therapy (OAT) with warfarin causes a partial deficiency of vitamin K-dependent factors, its effect on clot lysability remains unclear. OBJECTIVES: To evaluate plasma and blood fibrinolytic capacity in patients under stable OAT (n = 221) as compared with controls (n = 132). METHODS: Fibrinolysis resistance of plasma (turbidimetry) and blood (thromboelastography) clots was calculated as the lysis time of tissue factor-induced clots exposed to 30 and 100 ng mL(-1) t-PA, respectively. RESULTS: Plasma PAI-1 was similar in the two groups, whereas TAFI was slightly lower in patients. OAT plasma clots lysed faster than controls (P = 0.001). The addition of the TAFIa inhibitor PTCI reduced lysis time by 14% in OAT and 34% in controls, and the difference between the groups disappeared. Similar data were obtained with blood clots. Thrombin and TAFIa generation in OAT plasma amounted to roughly 50% of controls, supporting a reduced thrombin-dependent TAFI activation. Clot resistance of OAT plasma was normalized by Ba-citrate plasma eluate or prothrombin but not by BaSO(4) serum eluate, rFVIIa or FX. Surprisingly, circulating levels of TAFIa and its inactive derivative TAFIai were higher in warfarin patients (P < 0.0001) and correlated with plasmin-antiplasmin (P = 0.0001) but not with prothrombin F(1) (+) (2) . CONCLUSIONS: OAT enhances both plasma and blood fibrinolysis by reducing thrombin-dependent TAFI activation, a phenomenon largely determined by low prothrombin levels. At variance with in vitro data, 'basal' in vivo TAFIa/ai levels seem related to plasmin rather than thrombin generation.

Factors associated with access to antiviral treatment in a multicentre cross-sectional study of patients with chronic hepatitis B in Italy.

A multicentre cross-sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg-positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1-1.3, P < 0.001), HBeAg positivity (aOR 1.8, 95% CI 1.1-2.8, P < 0.001), cirrhosis (aOR 3.6, 95% CI 2-6.3, P = 0.012), HDV (aOR 1.6, 95% CI 1.02-2.5, P = 0.042) and HIV positivity (aOR 6.5, 95% CI 4-10.8, P < 0.001). Conversely, a decreased chance was associated with female gender (aOR 0.6, 95% CI 0.5-0.7, P < 0.001), immigration (aOR 0.6, 95% CI 0.5-0.9, P = 0.009), alcohol consumption (aOR 0.7, 95% CI 0.5-0.98, P = 0.04) and HCV positivity (aOR 0.5, 95% CI 0.3-0.8, P = 0.005). Our study shows that Italian IDCs treat a high percentage of patients with CHB. Nevertheless, disparities exist which are not related to the severity of disease limiting access to antiviral therapy of CHB, even in a country with a universal healthcare system.

Evaluation of immediate impact of cane use on energy expenditure during gait in patients with knee osteoarthritis.

PURPOSE: The aim of the present study was to assess the immediate impact of cane use on energy expenditure during gait in patients with knee OA analyzing VO(2). METHODS: An observational, cross-sectional study was carried out on 64 symptomatic patients with a diagnosis of knee OA. The assessment of energy expenditure was performed through an analysis of expired gases using the portable K4 apparatus (Cosmed, Model K4 b2, Italy) during the six-min walk test (6MWT). Two tests were performed with a cane and two without a cane on two different days within a seven-day period. RESULTS: The patients walked farther on the test without the cane (p<0.001). Oxygen expenditure (VO(2)) and the O(2) cost of walking at the end of the 6MWT increased approximately 50% and 80% during cane-assisted gait when compared to gait without the use of a cane (p<0.001). Pain (Borg scale) decreased approximately 20% at the end of the 6MWT with cane-assisted gait in comparison to gait without a cane (p<0.001). CONCLUSION: Cane use causes an immediate increase in energy expenditure (VO(2)) during gait and O(2) cost of walking and an immediate decrease of pain during gait. It is necessary to do a more prolonged follow up in order to assess the impact of daily cane use on energy expenditure among these patients and determine whether adaptation occurs. Furthermore, it is necessary to study whether daily cane use has a positive impact on important parameters in these patients, such as pain, function and quality of life.

Impact of cane use on pain, function, general health and energy expenditure during gait in patients with knee osteoarthritis: a randomised controlled trial.

OBJECTIVE: To assess the impact of daily cane use during gait in relation to pain, function, general health and energy expenditure among patients with knee osteoarthritis. METHOD: Sixty-four patients were randomly assigned to an experimental group (EG) or control group (CG). The EG used a cane every day for 2 months, whereas the CG did not use a cane in this period. The first outcome was pain and the second were function (Lequesne and WOMAC), general health (SF-36) and energy expenditure (gas analysis during the 6-minute walk test (6MWT) with and without a cane). Evaluations were performed at baseline, 30 and 60 days. RESULTS: The groups were homogeneous for all parameters at baseline. Compared with the CG, the EG significantly improved pain (ES 0.18), function - Lequesne (ES 0.13), some domains of SF-36 (role physical, ES 0.07 and bodily pain, ES 0.08) and distance on the 6MWT with the cane (ES 0.16). At the end of the 6MWT with the cane, the EG significantly improved energy expenditure (ES 0.21), carbon dioxide production (ES 0.12) and metabolic equivalents (ES 0.15) compared with the CG. CONCLUSION: A cane can be used to diminish pain, improve function and some aspects of quality of life in patients with knee osteoarthritis. The prescription of a cane should take into account the substantial increase in energy expenditure in the first month of use, whereas energy expenditure is no longer a factor for concern by the end of the second month due to adaptation to cane use. The trial was registered in clinicaltrials.gov (NCT00698412).

The role of thrombin activatable fibrinolysis inhibitor and factor XI in platelet-mediated fibrinolysis resistance: a thromboelastographic study in whole blood.

BACKGROUND: The resistance of platelet-rich thrombi to fibrinolysis is generally attributed to clot retraction and platelet PAI-1 release. The role of TAFI in platelet-mediated resistance to lysis is unclear. OBJECTIVE: We investigated the contribution of TAFI to the antifibrinolytic effect of platelets in whole blood by thromboelastography. METHODS: Platelet-poor (PP-WB, < 40 × 10(3) µL(-1) ) and platelet-rich (PR-WB, > 400 × 10(3) µL(-1) ) blood samples were obtained from normal human blood (N-WB, 150-220 × 10(3) µL(-1) ). Clot lysis time was measured by thromboelastography in recalcified blood supplemented with t-PA (100 ng mL(-1) ) and tissue factor (1:1000 Recombiplastin). RESULTS: t-PA-induced lysis time increased in parallel with platelet concentration (up to 3-fold). Neutralization of TAFI, but not of PAI-1, shortened the lysis time by ∼ 50% in PR-WB and by < 10% in PP-WB. Accordingly, prothrombin F1+2 and TAFIa accumulation was greater in PR-WB than in PP-WB. A similar TAFI-dependent inhibition of fibrinolysis was observed when clot retraction was prevented by cytochalasin D or abciximab, or when platelet membranes were tested. Moreover, in blood with an intact contact system, platelet-mediated fibrinolysis resistance was attenuated by an anti-FXI but not by an anti F-XII antibody. Finally, platelets made the clots resistant to the profibrinolytic effect of heparin concentrations displaying a strong anticoagulant activity. CONCLUSIONS: Our data indicate that TAFI activation is one major mechanism whereby platelets make clots resistant to fibrinolysis and underscore the importance of TAFI inhibitors as new antithrombotic agents.

Detection of enteroviruses from urban sewage in Parma.

BACKGROUND AND AIM OF THE WORK: The human enteroviruses (EV) are the most common and widespread human viruses in the world. They have bowel as their natural habitat and they can spread in the environment through the faecal excretion. In the continental climate Regions these viruses may cause epidemic outbreaks in summer and fall, while in the tropical Regions the EV infections present a high incidence during all year. The symptoms can be minor or subclinic, but they can be also associated to rare and serious diseases. The aim of this study was to evaluate the environmental circulation of polioviruses and non-polio enteroviruses (NPEV) using standard methods of urban wastewater surveillance recommended by the WHO. METHODS: A total of 188 wastewater samples were collected between February 2005 and December 2008 from two sewage treatment plants in Parma. The sampling was carried out twice a month. Environmental variables were collected for each day of sampling. RESULTS: Out of the 188 examined wastewater samples, 78.7% were positive to the enterovirus research. One out of the 148 positive samples was identified as poliovirus Sabin-like type 3. The remaining 147 positive samples were enteroviruses non polio: Coxsakieviruses and Echoviruses. All Coxsakieviruses isolated were of type B. CONCLUSIONS: The proposed method has shown high sensibility, also in presence of very low expected prevalence of vaccine poliovirus. It allows to verify the kind and relative frequency of enteric viruses circulating in the country, whose characteristics (virulence and pathogenicity) may vary with reference to a different epidemiologic and demographic structure of the resident population.

[Hospital admission of subjects with chronic obstructive bronchopulmonary disease (COPD) and air pollution in the city of Parma (Italy). A preliminary analysis]. / Funzionalità respiratoria in soggetti con Broncopneumopatia Cronica Ostruttiva (BPCO) e inquinamento atmosferico nella città di Parma Analisi preliminare.

A study was conducted in subjects admitted to hospital for chronic obstructive bronchopulmonary disease (COPD) in the city of Parma (Italy). The aim was to evaluate changes in patients' percent vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), as a function of changing degrees of atmospheric pollution as measured by PM10, NO2 and O3 concentrations in the outside air. Study results revealed an association between PM10 concentrations and hospital admissions for COPD. Statistically significant differences were found between PM10 concentrations measured three-four days before admission and in days not followed by admission to hospital. Regression analysis between PM10 concentrations at 24, 48, 72, and 96 hours before admission and respiratory function showed a significant association between FVC% and FEV1% and PM10 concentrations at 96 hours. The relative risk was calculated to be 1.016 (95% confidence intervals: 1.001-1.032), which corresponds to a 1.6% increased risk of admission to hospital for COPD for each unit increase in PM10 concentration in the outside air.

Dabigatran enhances clot susceptibility to fibrinolysis by mechanisms dependent on and independent of thrombin-activatable fibrinolysis inhibitor.

BACKGROUND: Anticoagulants are expected to promote fibrinolysis by counteracting the antifibrinolytic effects of thrombin, which include thrombin-activatable fibrinolysis inhibitor (TAFI) activation and clot structure enhancement. However, the efficiency of anticoagulants may vary remarkably, and the ability of direct thrombin inhibitors to facilitate clot lysis remains controversial. OBJECTIVE: To evaluate the profibrinolytic effect of dabigatran, a new, direct thrombin inhibitor, using different in vitro models. METHODS AND RESULTS: The resistance of tissue factor-induced plasma clots to fibrinolysis by exogenous tissue-type plasminogen activator (t-PA) (turbidimetric method) was reduced by dabigatran in a concentration-dependent manner, with > or = 50% shortening of lysis time at clinically relevant concentrations (1-2 microm). A similar effect was observed in the presence of low (0.1 and 1 nm) but not high (10 nm) concentrations of thrombomodulin. Acceleration of clot lysis by dabigatran was associated with a reduction in TAFI activation and thrombin generation, and was largely, although not completely, negated by an inhibitor of activated TAFI, potato tuber carboxypeptidase inhibitor. The assessment of the viscoelastic properties of clots showed that those generated in the presence of dabigatran were more permeable, were less rigid, and consisted of thicker fibers. The impact of these physical changes on fibrinolysis was investigated using a model under flow conditions, which demonstrated that dabigatran made the clots markedly more susceptible to flowing t-PA, by a mechanism that was largely TAFI-independent. CONCLUSIONS: Dabigatran, at clinically relevant concentrations, enhances the susceptibility of plasma clots to t-PA-induced lysis by reducing TAFI activation and by altering the clot structure. These mechanisms might contribute to the antithrombotic activity of the drug.

Inhaled ammonium persulphate inhibits non-adrenergic, non-cholinergic relaxations in the guinea pig isolated trachea.

BACKGROUND: Persulphates can act both as irritants and sensitizers in inducing occupational asthma. A dysfunction of nervous control regulating the airway tone has been hypothesized as a mechanism underlying bronchoconstriction in asthma. OBJECTIVES: It was the aim of this study to investigate whether inhaled ammonium persulphate affects the non-adrenergic, non-cholinergic (NANC) inhibitory innervation, the cholinergic nerve-mediated contraction or the muscular response to the spasmogens, carbachol or histamine, in the guinea pig epithelium-free, isolated trachea. METHODS: Male guinea pigs inhaled aerosols containing ammonium persulphate (10 mg/m(3) for 30 min for 5 days during 3 weeks). Control animals inhaled saline aerosol. NANC relaxations to electrical field stimulation at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes. Drugs inactivating peptide transmission, nitric oxide synthase, carbon monoxide production by haem oxygenase-2 and soluble guanylyl cyclase were used to assess the involvement of various inhibitory neurotransmitters. Carbachol and histamine cumulative concentration-response curves were obtained. RESULTS: In both groups, nitric oxide and carbon monoxide participated to the same extent as inhibitory neurotransmitters. In exposed animals, the tracheal NANC relaxations were reduced to 45.9 +/- 12.1% (p < 0.01). The cholinergic nerve-mediated contractions to electrical field stimulation and the muscular response to histamine were not modified by ammonium persulphate exposure. The muscular response to carbachol was unaffected up to 1 microM. Conversely, the response to the maximal concentration of carbachol (3 microM) was increased (p < 0.01). CONCLUSION: Ammonium persulphate inhalation at high concentrations impairs the nervous NANC inhibitory control in the guinea pig airways. This may represent a novel mechanism contributing to persulphate-induced asthma.