Effect of high dose verapamil administration on the Ca2+ channel density in rat cardiac tissue

NRC publication: Ye

Duration of gargling and rinsing among frequent mouthwash users: a cross-sectional study

OBJECTIVE: To examine the rinsing and gargling mouthwash practices among frequent mouthwash users to determine if there are differences in use between gender, sexual orientation and sex work status. DESIGN: Cross-sectional study. SETTING: Data obtained from patients attending a sexual health centre located in Melbourne, Australia. PARTICIPANTS: 200 frequent mouthwash users (four or more times per week), 50 for each of the following patient groups: men who have sex with men (MSM), female sex workers (FSW), females who are not sex workers and men who have sex with women only (MSW). Participants were observed and audio recorded using mouthwash. PRIMARY AND SECONDARY OUTCOME MEASURES: Descriptive analyses were conducted to calculate the median age, time rinsing and gargling, amount of mouthwash used and proportion of participants who rinsed, gargled or both, as determined from the audio files. Kruskal-Wallis H test and χ2 test were used to examine differences between the patient groups. RESULTS: Median age was 28 years (IQR: 24-33). During the study, most (n=127; 63.5%) rinsed and gargled, but 70 (35.0%) rinsed only and three (1.5%) gargled only. Median time rinsing was 13.5 s (IQR: 8.5-22.0 s), gargling was 4.0 s (IQR: 2.5-6.0 s) and the median total duration was 17.0 s (IQR: 11.5-25.8 s). Median duration of mouthwash did not differ significantly between the groups (females not sex workers: 18.8 s (IQR: 12.5-24.5 s); FSW: 14.0 s (9.0-22.0 s); MSM: 22.3 s (13.0-26.5 s); MSW: 15.8 s (12.0-25.0 s); p=0.070) but males used mouthwash longer than females (median 20.3 s compared with 15.5 s; p=0.034). The median volume of mouthwash used was 20 mL (IQR: 15-27 mL). And most (n=198; 99.0%) did not dilute mouthwash with water. CONCLUSION: Over a quarter of frequent users do not gargle mouthwash at all (35%) and used it for a substantially shorter period of time than it was used in the randomised trial (1 min) where it was shown to be effective at inhibiting Neisseria gonorrhoeae growth. Our findings suggest that many frequent mouthwash users do not follow the manufacturer instructions for using mouthwash and may not use mouthwash in a way that was shown to reduce the growth of oropharyngeal gonorrhoea

Synthetic adventures along a Rocky Mountain road

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Oral, Vaginal and Anal Sexual Practices among Heterosexual Males and Females Attending a Sexual Health Clinic: A Cross-Sectional Survey in Melbourne, Australia

Sex practices among heterosexuals are not well studied. We aimed to explore sexual practices among heterosexuals attending a sexual health clinic. This cross-sectional survey was conducted at Melbourne Sexual Health Centre between March and April 2019. Data were collected on kissing, oral sex (fellatio or cunnilingus), vaginal sex, anal sex and rimming in the previous 3 months. Univariable and multivariable logistic regression analyses were performed to examine the associations between engaging in anal sex and other sex practices. There were 709 participants (333 men; 376 women) who were eligible and completed the survey (response rate was 24.6%). In the past 3 months, most participants had had vaginal sex (n = 677; 95.5%), with a mean of 3.0 (standard deviation (SD): 3.9) vaginal sex partners, and half reported engaging in condomless vaginal sex in the past 3 months (n = 358; 50.1%). A total of 135 (19.0%) participants had had anal sex, with a mean of 1.3 (SD: 1.0) anal sex partners, with 63.5% (n = 94) engaging in any condomless anal sex in the past 3 months. Most participants (n = 637, 89.8%) had received oral sex in the past 3 months; this proportion did not differ by age group or gender. Women (n = 351, 93.4%) were more likely to perform oral sex than men (n = 275; 82.6% men) (p < 0.001) and to have received rimming (26.6% women vs. 12.6% men; p < 0.001). Men were more likely to have performed rimming (25.5% men vs. 9.3% women; p < 0.001). After adjusting for age, number of partners and sexual practice, anal sex was associated with being ≥35 years (adjusted odds ratio (aOR): 2.3; 95% CI: 1.2–4.2), receiving rimming (aOR: 3.8; 95% CI: 2.4–6.0) and performing rimming (aOR: 2.8; 95% CI: 1.8–4.6). Rimming and anal sex are practiced by one-fifth or more of heterosexuals. Older heterosexuals were more likely to engage in anal sex and to perform rimming. Future research should consider the benefits of testing extragenital sites where appropriate

NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity

A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the μ-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the μ-opioid GPCR was predicated on the modulatory role of nitric oxide on μ-opioid receptor function. Structure–activity relationship studies yielded lead compound <b>24</b> with excellent nNOS inhibitory activity (IC₅₀ = 0.44 μM), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent μ-opioid binding affinity, <i>K</i>_i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC₅₀ = 0.34 μM). This work represents a novel approach in the development of new analgesics for the treatment of pain

Modulation of cardiac performance by amiloride and several selected derivatives of amiloride

NRC publication: Ye

Aryl trihydroxyborates: Easily isolated discrete species convenient for direct application in coupling reactions

A conceptually and practically simple alternative approach to the use of arylboron species as the organometallic component in cross-coupling processes is described whereby trihydroxyborate salts are isolated and directly employed. The protocol derives practical benefit from the ease and convenience of the isolation and subsequent use of the discrete borate salts, eliminates the need for additional base, and aids the use of correct reaction stoichiometry

First-in-Class, Dual-Action, 3,5-Disubstituted Indole Derivatives Having Human Nitric Oxide Synthase (nNOS) and Norepinephrine Reuptake Inhibitory (NERI) Activity for the Treatment of Neuropathic Pain

A family of different 3,5-disubstituted indole derivatives having 6-membered rings were designed, synthesized, and demonstrated inhibition of human nitric oxide synthase (NOS) with norepinephrine reuptake inhibitory activity (NERI). The structure–activity relationship (SAR) within the cyclohexane ring showed the <i>cis</i>-isomers to be more potent for neuronal NOS and selective over endothelial NOS compared to their <i>trans</i>-counterparts. Compounds, such as <i>cis</i>-(+)-<b>37</b>, exhibited dual nNOS and NET inhibition (IC₅₀ of 0.56 and 1.0 μM, respectively) and excellent selectivity (88-fold and 12-fold) over eNOS and iNOS, respectively. The lead compound (<i>cis</i>-(+)-<b>37</b>) showed lack of any direct vasoconstriction or inhibition of ACh-mediated vasorelaxation in isolated human coronary arteries. Additionally, <i>cis</i>-(+)-<b>37</b> was effective at reversing both allodynia and thermal hyperalgesia in a standard Chung (spinal nerve ligation) rat neuropathic pain model. Overall, the data suggest that <i>cis</i>-(+)-<b>37</b> is a promising dual action development candidate having therapeutic potential for the treatment of neuropathic pain