Comparison of CGS 15943, ZM 241385 and SCH 58261 as antagonists at human adenosine receptors

Three structurally related non-xanthine compounds, CGS 15943, ZM 241385 and SCH 58261, are potent A_2A adenosine receptor antagonists and have been used as tools in many pharmacological studies. We have now characterized their affinity and selectivity profile on human adenosine receptors stably transfected into either CHO cells (A₁ and A_2B receptors) or HEK-293 cells (A_2A and A₃ receptors). In binding studies using [³H]SCH 58261 as a radioligand, the three compounds were equally potent at A_2A receptors, their K _i value being less than 1 nM. Affinity for A₁ and A₃ receptors was measured using [³H]DPCPX and [¹²⁵I]AB-MECA as radioligands. Given the lack of selective ligands, interaction with A_2B receptors was assessed using the cAMP accumulation assay following stimulation by the adenosine receptor agonist N-ethylcarboxamidoadenosine (NECA). CGS 15943 was almost as potent at A₁ receptors (K _i 3.5 nM) as at A_2A receptors, showed moderate affinity for A₃ receptors (K _i 95 nM) and also interacted with A_2B receptors (K _i 44 nM; pA₂ 7.5). ZM 241385 showed little affinity for A₁ receptors (K _i 255 nM), and did not interact with A₃ receptors (K _i>10 μM); however, it displayed moderate affinity for A_2B receptors (K _i 50 nM; pA₂ 7.3). SCH 58261 had weak affinity for A₁ receptors (K _i 287 nM), no interaction with A₃ receptors (K _i>10 μM), and showed negligible interaction with A_2B receptors (K _i 5 μM; pA₂ 6.0). These data indicate that SCH 58261 is the most selective A_2A antagonist currently available. Moreover, the different receptor selectivity of these three chemically related compounds provides useful information to progress with structure-activity relationship studies. Received: 2 July 1998 / Accepted: 6 October 1998     

Sexual Debut Among Heterosexual Men of African and Caribbean Descent: Are the Youth Initiating Sex Earlier than the Older Generation?

Although age at first sex is considered a measure of sexual risk and vulnerability for HIV infection, there is a dearth of literature on age at sexual debut in the Canadian context. This study examined time variations to first sex among heterosexual African, Caribbean, and Black (ACB) men in four Ontarian cities. A population-based retrospective survey (n?=?879) on timing to first sexual intercourse was conducted between 2018 and 2019 among self-identified heterosexual ACB men 16 years or older and residing in London, Ottawa, Toronto or Windsor. We used the lognormal survival analysis technique to examine variations in time to first sexual intercourse among age cohorts and between cities. The findings showed a generational shift in the pattern of sexual initiation, with younger heterosexual ACB men initiating sexual intercourse earlier compared with those currently older than 50 years. We observed those between 16 and 19 years, 20 and 29 years, and 30 and 39 years of age to have significantly higher risk ratios of TR?=?0.852, TR?=?0.869, and TR?=?0.855, respectively. At city level, the results show marked spatial variations, with youth in cities of Toronto, Ottawa, and London at the highest risk of early sexual debut relative to those in Windsor. Early initiation of first sexual intercourse among heterosexual ACB youth was observed with those in the larger cities being at a relatively higher risk. There is the need for programs aimed at delaying sexual debut among youth in general. It is, however, important to recognize the relative risk of those in the larger cities.

     

Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells

The potency of adenosine and inosine as agonists at human adenosine receptors was examined in a functional assay using changes in cyclic AMP (cAMP) formation in intact Chinese hamster ovary (CHO) cells stably transfected with the human A1, A2A, A2B, and A3 receptors. Adenosine increased cAMP formation in cells expressing the A2A (EC(50): 0.7 microM) and A2B (EC(50): 24 microM) receptors and inhibited forskolin (0.3-3 microM)-stimulated cAMP formation in cells expressing the A1 (EC(50): 0.31 microM) and A3 receptors (EC(50): 0.29 microM). The potency of adenosine at the A2A and A2B receptors was not altered by the presence of the uptake inhibitor nitrobenzylthioinosine (NBMPR), whereas it was increased about 6-fold by NBMPR at the A1 and A3 receptors. In the presence of NBMPR, inosine was a potent agonist (EC(50): 7 and 0.08 microM at the A1 and A3 receptors, respectively), but with low efficacy especially at the A3 receptors. No effect of inosine was seen at the A(2) receptors. Caffeine, theophylline, and paraxanthine shifted the dose-response curve for adenosine at the A1, A2A, and A2B receptors. These results indicate that adenosine is the endogenous agonist at all human adenosine receptors and that physiological levels of this nucleoside can activate A1, A2A, and A3 receptors on cells where they are abundantly expressed, whereas pathophysiological conditions are required to stimulate A2B receptors to produce cyclic AMP.     

Exposure to mass media family planning messages among post-delivery women in Nigeria: testing the structural influence model of health communication

Objectives: While media campaigns are documented to be useful for increasing the uptake of family planning, very little is known about the population prevalence and correlates of exposure to mass media family planning messages among post-delivery women in Nigeria. We aimed to address this void by exploring the underlying factors that explain disparities in exposure to mass media family planning messages among post-delivery women in Nigeria.

Methods: Our study was a secondary analysis of the Nigeria Demographic and Health Survey, a nationally representative dataset of men and women. Using logistic regression techniques and drawing on the structural influence model of health communication, we explored post-delivery women’s (N?=?13,889) exposure to mass media family planning messages in Nigeria.

Results: We found that 32% of post-delivery women were exposed to family planning messages on mass media in Nigeria. At the bivariate level, Muslim women were less likely to be exposed to mass media family planning messages compared with Christian women (odds ratio [OR] 0.39; 95% confidence interval [CI] 0.36, 0.41); however, the OR became positive once we controlled for structural determinants such as household wealth and education (OR 1.22; 95% CI 1.07, 1.40). In the multivariate analysis, we found that traditionalist women (OR 0.29; 95% CI 0.14, 0.58) and women from rural areas (OR 0.69; 95% CI 0.62, 0.76) were less likely to be exposed to such messages. Moreover, richer, better educated, and employed women were more likely to be exposed to mass media family planning messages compared with their poorer, less educated and unemployed counterparts. Similarly, living in the South West region was positively associated with higher odds of being exposed to such messages.

Conclusion: Findings were largely consistent with the structural influence model of health communication, as highlighted by inequalities in exposure to mass media messages. Based on these findings, we provide several policy recommendations.     

The influence of the Community‐based Health Planning and Services (CHPS) program on community health sustainability in the Upper West Region of Ghana

Ghana introduced Community‐based Health Planning and Services (CHPS) to improve primary health care in rural areas. The extension of health care services to rural areas has the potential to increase sustainability of community health. Drawing on the capitals framework, this study aims to understand the contribution of CHPS to the sustainability of community health in the Upper West Region of Ghana—the poorest region in the country. We conducted in‐depth interviews with community members (n = 25), key informant interviews with health officials (n = 8), and focus group discussions (n = 12: made up of six to eight participants per group) in six communities from two districts. Findings show that through their mandate of primary health care provision, CHPS contributed directly to improvement in community health (eg, access to family planning services) and indirectly through strengthening social, human, and economic capital and thereby improving social cohesion, awareness of health care needs, and willingness to take action at the community level. Despite the current contributions of CHPS in improving the sustainability of community health, there are several challenges, based on which we recommend, that government should increase staffing and infrastructure in order to strengthen and maintain the functionality of CHPS.