Vascular smooth muscle contractility assays for inflammatory and immunological mediators

The blood vessels are one of the important target tissues for the mediators of inflammation and allergy; further cytokines affect them in a number of ways. We review the use of the isolated blood vessel mounted in organ baths as an important source of pharmacological information. While its use in the bioassay of vasoactive substances tends to be replaced with modern analytical techniques, contractility assays are effective to evaluate novel synthetic drugs, generating robust potency and selectivity data about agonists, partial agonists and competitive or insurmountable antagonists. For instance, the human umbilical vein has been used extensively to characterize ligands of the bradykinin B2 receptors. Isolated vascular segments are live tissues that are intensely reactive, notably with the regulated expression of gene products relevant for inflammation (e.g., the kinin B1 receptor and inducible nitric oxide synthase). Further, isolated vessels can be adapted as assays of unconventional proteins (cytokines such as interleukin-1, proteases of physiopathological importance, complement-derived anaphylatoxins and recombinant hemoglobin) and to the gene knockout technology. The well known cross-talks between different cell types, e.g., endothelium-muscle and nerve terminal-muscle, can be extended (smooth muscle cell interaction with resident or infiltrating leukocytes and tumor cells). Drug metabolism and distribution problems can be modeled in a useful manner using the organ bath technology, which, for all these reasons, opens a window on an intermediate level of complexity relative to cellular and molecular pharmacology on one hand, and in vivo studies on the other

Energy conservation and the promotion of Legionella pneumophila growth: The probable role of heat exchangers in a nosocomial outbreak

OBJECTIVE To determine the source of a Legionella pneumophila serogroup 5 nosocomial outbreak and the role of the heat exchanger installed on the hot water system within the previous year. SETTING A 400-bed tertiary care university hospital in Sherbrooke, Canada. METHODS Hot water samples were collected and cultured for L. pneumophila from 25 taps (baths and sinks) within wing A and 9 taps in wing B. Biofilm (5) and 2 L water samples (3) were collected within the heat exchangers for L. pneumophila culture and detection of protists. Sequence-based typing was performed on strain DNA extracts and pulsed-field gel electrophoresis patterns were analyzed. RESULTS Following 2 cases of hospital-acquired legionellosis, the hot water system investigation revealed a large proportion of L. pneumophila serogroup 5 positive taps (22/25 in wing A and 5/9 in wing B). High positivity was also detected in the heat exchanger of wing A in water samples (3/3) and swabs from the heat exchanger (4/5). The outbreak genotyping investigation identified the hot water system as the source of infections. Genotyping results revealed that all isolated environmental strains harbored the same related pulsed-field gel electrophoresis pattern and sequence-based type. CONCLUSIONS Two cases of hospital-acquired legionellosis occurred in the year following the installation of a heat exchanger to preheat hospital hot water. No cases were reported previously, although the same L. pneumophila strain was isolated from the hot water system in 1995. The heat exchanger promoted L. pneumophila growth and may have contributed to confirmed clinical cases. Infect. Control Hosp. Epidemiol. 2016;1475-1480

Transforming Growth Factor: β Signaling Is Essential for Limb Regeneration in Axolotls

Axolotls (urodele amphibians) have the unique ability, among vertebrates, to perfectly regenerate many parts of their body including limbs, tail, jaw and spinal cord following injury or amputation. The axolotl limb is the most widely used structure as an experimental model to study tissue regeneration. The process is well characterized, requiring multiple cellular and molecular mechanisms. The preparation phase represents the first part of the regeneration process which includes wound healing, cellular migration, dedifferentiation and proliferation. The redevelopment phase represents the second part when dedifferentiated cells stop proliferating and redifferentiate to give rise to all missing structures. In the axolotl, when a limb is amputated, the missing or wounded part is regenerated perfectly without scar formation between the stump and the regenerated structure. Multiple authors have recently highlighted the similarities between the early phases of mammalian wound healing and urodele limb regeneration. In mammals, one very important family of growth factors implicated in the control of almost all aspects of wound healing is the transforming growth factor-beta family (TGF-β). In the present study, the full length sequence of the axolotl TGF-β1 cDNA was isolated. The spatio-temporal expression pattern of TGF-β1 in regenerating limbs shows that this gene is up-regulated during the preparation phase of regeneration. Our results also demonstrate the presence of multiple components of the TGF-β signaling machinery in axolotl cells. By using a specific pharmacological inhibitor of TGF-β type I receptor, SB-431542, we show that TGF-β signaling is required for axolotl limb regeneration. Treatment of regenerating limbs with SB-431542 reveals that cellular proliferation during limb regeneration as well as the expression of genes directly dependent on TGF-β signaling are down-regulated. These data directly implicate TGF-β signaling in the initiation and control of the regeneration process in axolotls

Re-evaluation of blood mercury, lead and cadmium concentrations in the Inuit population of Nunavik (Québec): a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Arctic populations are exposed to mercury, lead and cadmium through their traditional diet. Studies have however shown that cadmium exposure is most often attributable to tobacco smoking. The aim of this study is to examine the trends in mercury, lead and cadmium exposure between 1992 and 2004 in the Inuit population of Nunavik (Northern Québec, Canada) using the data obtained from two broad scale health surveys, and to identify sources of exposure in 2004.</p> <p>Methods</p> <p>In 2004, 917 adults aged between 18 and 74 were recruited in the 14 communities of Nunavik to participate to a broad scale health survey. Blood samples were collected and analysed for metals by inductively coupled plasma mass spectrometry, and dietary and life-style characteristics were documented by questionnaires. Results were compared with data obtained in 1992, where 492 people were recruited for a similar survey in the same population.</p> <p>Results</p> <p>Mean blood concentration of mercury was 51.2 nmol/L, which represent a 32% decrease (p < 0.001) between 1992 and 2004. Mercury blood concentrations were mainly explained by age (partial r²= 0.20; p < 0.0001), and the most important source of exposure to mercury was marine mammal meat consumption (partial r²= 0.04; p < 0.0001). In 2004, mean blood concentration of lead was 0.19 μmol/L and showed a 55% decrease since 1992. No strong associations were observed with any dietary source, and lead concentrations were mainly explained by age (partial r²= 0.20.; p < 0.001). Blood cadmium concentrations showed a 22% decrease (p < 0.001) between 1992 and 2004. Once stratified according to tobacco use, means varied between 5.3 nmol/L in never-smokers and 40.4 nmol/L in smokers. Blood cadmium concentrations were mainly associated with tobacco smoking (partial r²= 0.56; p < 0.0001), while consumption of caribou liver and kidney remain a minor source of cadmium exposure among never-smokers.</p> <p>Conclusion</p> <p>Important decreases in mercury, lead and cadmium exposure were observed. Mercury decrease could be explained by dietary changes and the ban of lead cartridges use likely contributed to the decrease in lead exposure. Blood cadmium concentrations remain high and, underscoring the need for intensive tobacco smoking prevention campaigns in the Nunavik population.</p

Consultations médicales et types de services de santé utilisés dans les deux années précédant le suicide auprès des Québécois diagnostiqués avec et sans troubles mentaux et troubles avec utilisation de substances

Les objectifs de cette étude étaient de décrire l’utilisation des services de santé auprès des personnes décédées par suicide au Québec, diagnostiquées ou non avec troubles mentaux (TM) et dépendances (D) (TM/D), répertoriées dans les bases de données administratives (BDA), et un groupe témoin de Québécois vivants diagnostiqués avec un TM/D. Les données proviennent du Système intégré de surveillance des maladies chroniques du Québec (SISMACQ), qui jumelle les bases de données des services médicaux rémunérés à l’acte et d’hospitalisations. La population source est composée de Québécois âgés de 15 ans et plus assurés entre le 1er avril 1996 et le 31 mars 2013 par la Régie de l’assurance maladie du Québec (RAMQ). Les résultats montrent que les cas de suicide avec et sans TM/D avaient moins tendance à consulter (oui/non) dans l’année qui précède le décès et avaient moins tendance à être de grands utilisateurs de services de santé (c’est-à-dire au moins 4 visites) que le groupe témoin des personnes vivantes. Les cas de suicide sans TM/D diagnostiqués avaient plus tendance à se rendre uniquement à l’urgence. Le groupe de personnes décédées par suicide avec TM/D avait plus tendance à consulter en ambulatoire et à l’urgence que les deux autres groupes. Le groupe témoin des personnes vivantes avec un TM/D était plus enclin à consulter en ambulatoire seulement. Des études futures devraient se focaliser sur des analyses multivariées afin de comparer les profils d’utilisation des services de santé et les raisons de consultations des cas de suicide et les personnes vivantes avec différents TM/D.Objectives Population based studies on linked health administrative databases (HADBs) characterizing those who die by suicide and their use of health services are rare. The objectives of this study were to describe the use of health services among people who died by suicide in Quebec, with and without previously receiving a mental disorder (MD) and dependencies (D) (MD/D) diagnosis, and (2) living Quebecers diagnosed with MD/D.Methods This study is based on an analysis of data from the Integrated Chronic Disease Surveillance System of Quebec (SISMACQ), which combines databases on outpatient medical and emergency services and hospitalizations. The population of the study consists of Quebecers aged 15 years and over and insured between April 1, 1996 and March 31, 2013 under the Régie de l’assurance maladie du Québec (RAMQ). For the purposes of this study, the 7 years preceding suicide were examined in the HADBDS for the three following cohort groups: (i) cases of suicide with a diagnosed MD/D in the 7 years preceding the date of death; (ii) cases of suicide without a MD/D diagnosis in the 7 years preceding the date of death; and (iii) a control group of living persons at the time of death of the suicide case (5 controls, 1 case) with a MD/D diagnosis within 7 years matched by region, sex and age group of the case.Results The results show that cases of suicide without a MD/D (about 25% of suicide cases) were less likely to have consulted than those with a MD/D. Suicide cases with and without a MD/D were less likely to be heavy users of ambulatory health services (≥ 4 visits) than matched living controls. They were also more likely to consult for a physical disorder alone and less likely to consult for mental health reasons. Compared to cases of suicide with a MD/D, suicide cases without MD/D were less likely to be hospitalized and more likely to have visited only an emergency room. Suicide cases diagnosed with a MD/D were more likely to be hospitalized and use emergency services alone than the other two groups. Matched living controls with a MD/D were more likely to use outpatient services alone.Conclusions These results should be compared with those emerging from systematic suicide case audits. These show a prevalence of mental disorders of 90%, especially depression, personality disorders and substance use disorders. They also show deficits in the recognition and treatment of mental disorders, which would correspond to the 25% of cases of suicide in the HADBs not diagnosed in the last 7 years. Future studies should include multivariate analyses to better elucidate health service use trajectories and patient vulnerability profiles

MOESM1 of A multi-host approach to identify a transposon mutant of Pseudomonas aeruginosa LESB58 lacking full virulence

Additional file 1. All additional protocols, figures and tables cited in this article