Estimating the size of the population of persons who inject drugs in the island of Montréal, Canada, using a six-source capture-recapture model

BACKGROUND: To plan and implement services to persons who inject drugs (PWID), knowing their number is essential. For the island of Montréal, Canada, the only estimate, of 11,700 PWID, was obtained in 1996 through a capture-recapture method. Thirteen years later, this study was undertaken to produce a new estimate. METHODS: PWID were defined as individuals aged 14-65 years, having injected recently and living on the island of Montréal. The study period was 07/01/2009 to 06/30/2010. An estimate was produced using a six-source capture-recapture log-linear regression method. The data sources were two epidemiological studies and four drug dependence treatment centres. Model selection was conducted in two steps, the first focusing on interactions between sources and the second, on age group and gender as covariates and as modulators of interactions. RESULTS: A total of 1480 PWID were identified in the six capture sources. They corresponded to 1132 different individuals. Based on the best-fitting model, which included age group and sex as covariates and six two-source interactions (some modulated by age), the estimated population was 3910 PWID (95% confidence intervals (CI): 3180-4900) which represents a prevalence of 2.8 (95% CI: 2.3-3.5) PWID per 1000 persons aged 14-65 years. CONCLUSIONS: The 2009-2010 estimate represents a two-third reduction compared to the one for 1996. The multisource capture-recapture method is useful to produce estimates of the size of the PWID population. It is of particular interest when conducted at regular intervals thus allowing for close monitoring of the injection phenomenon.

Role of the human chymase (CMA1) in the conversion of big-endothelin-1 to endothelin-1 (1-31)

Abstract : The chymase-dependant pathway responsible for converting Big ET-1 to ET-1 was established in vitro. It has only been recently, in 2009, that our group demonstrated that the conversion of Big ET-1 to ET-1 (1-31) can occur in vivo in mice (Simard et al., 2009), knowing that ET-1 (1-31) is converted to ET-1 via NEP in vivo (Fecteau et al., 2005). In addition, our laboratory demonstrated in 2013 that mMCP-4, the murine analogue of human chymase, produces ET-1 (1-31) from the Big ET-1 precursor (Houde et al. 2013). Thus far, in the literature, there are no specific characterizations of recombinant chymases (human or murine). In fact, the group of Murakami published in 1995 a study characterizing the CMA1 (human chymase) in a chymostatin-dependent fashion, using Angiotensin I as a substrate (Murakami et al., 1995). However, chymostatin is a non-specific inhibitor of chymase. It has been shown that chymostatin can inhibit elastase, an enzyme that can convert Angiotensin I to Angiotensin II (Becari et al., 2005). Based on these observations, the proposed hypothesis in the present study suggests that recombinant as well as extracted CMA1 from LUVA (human mast cell line), in addition to soluble fractions of human aortas, convert Big ET-1 into ET-1 (1-31 ) in a TY-51469 (a chymase-specific inhibitor) sensitive manner. In a second component, we studied the enzyme kinetics of CMA1 with regard to the Big ET-1 and Ang I substrate. The affinity of CMA1 against Big ET-1 was greater compared to Ang I (KM Big ET- 1: 12.55 μM and Ang I: 37.53 μM). However, CMA1 was more effective in cleaving Ang I compared to Big ET-1 (Kcat / KM Big ET-1: 6.57 x 10-5 μM-1.s-1 and Ang I: 1.8 x 10-4 ΜM-1.s- 1). In a third component involving in vivo experiments, the pressor effects of Big ET-1, ET-1 and Ang I were tested in conscious mMCP-4 KO mice compared to wild-type mice. The increase in mean arterial pressure after administration of Big ET-1 was greater in wild-type mice compared to mMCP- 4 KO mice. This effect was not observed after administration of ET-1 and / or Ang I.