Methods: For the optimisation and validation protocol, β-cells were plated onto 35 mm plastic petri dishes and maintained in RPMI-1640 media supplemented with 10 mM glucose, 10% FCS and 25 mM of N-2-hydroxyethylpiperazine-N-ethanesulfonic acid (HEPES). The treatment effects of 10 mM glucose and 30 μM fluoxetine on KATP channels NPo of β-cells were assessed via cell-attached patch-clamp recordings. For hippocampus cell experiments, hippocampi were harvested from day 17 of maternal Lister-hooded rat foetus, and then transferred to a Ca2+ and Mg2+-free HEPES-buffered Hank's salt solution (HHSS). The dissociated cells were cultured and plated onto a 25 mm round cover glasses coated with poly-d-lysine (0.1 mg/mL) in a petri dish. The KATP channels NPo of hippocampus cells when perfused with 1 mM and 10 mM of KA were determined.
Results: NPo of β-cells showed significant decreasing patterns (P < 0.001) when treated with 10 mM glucose 0.048 (0.027) as well as 30 μM fluoxetine 0.190 (0.141) as compared to basal counterpart. In hippocampus cell experiment, a significant increase (P < 0.001) in mean NPo 2.148 (0.175) of neurons when applied with 1 mM of KA as compared to basal was observed.
Conclusion: The two concentrations of KA used in the study exerted contrasting effects toward the mean of NPo. It is hypothesised that KA at lower concentration (1 mM) opens more KATP channels, leading to hyperpolarisation of the neurons, which may prevent neuronal hyper excitability. No effect was shown in 10 mM KA treatment, suggesting that only lower than 10 mM KA produced significant changes in KATP channels. This implies further validation of KA concentration to be used in the future.
OBJECTIVE: The objective of this study is to evaluate the anti-cancer potential of the novel class of quinazoline tethered acetamide derivatives against six different cancer cell lines.
METHOD: A novel series of various substituted quinazolinone acetamides were synthesized through a feasible scheme. The synthetic scheme involves the conversion of benzoxazinone (from anthranilic acid and benzoyl chloride) intermediate to 3-amino quinazoline-4-one which is further converted to the final amide by tethering with the propionyl chloride employing Schotten-Baumann Reaction conditions. All the synthesized derivatives characterized by IR, 1HNMR and MASS spectral methods and anti-cancer activity evaluated by employing MTT assay for six cancer cell lines and one normal human cell line.
RESULTS: All the synthesized compounds were screened for anti-cancer activity against six cancer cell lines, including A 549 (lung), DU 145 (prostate), HT 29 (colon), MCF-7 (breast), SiHA (cervical), B16F10 (mouse skin melanoma) and one normal human fibroblast cell lines. All the compounds displayed a decent cytotoxicity profile when compared with the standard drug, doxorubicin. Among the synthesized compounds (5a to 5n) tested, two compounds, 5f and 5g have demonstrated excellent cytotoxicity against SiHA and MCF-7 cancer cell lines.
CONCLUSION: Comparatively, most of the compounds displayed decent cytotoxicity potential relative to the standard drug, doxorubicin. Further investigations are needed to establish the detailed mechanism of action of the developed novel quinazolinone acetamides.
METHODS: As one voice, 13 main industry associations under the umbrella of APAC sent joint letters to our National Regulatory Authorities (NRAs) with a call to maintain regulatory agility and consider new ways of working. Consequently, APAC surveyed its member associations to measure regulatory agilities implemented by the NRAs during 2020 and 2021 in view of the pandemic.
RESULTS: This paper reports progress in implementing regulatory agility, e.g. the number of economies that can accept electronic Certificate of Pharmaceutical Products (eCPP) has reached 100% for the economies that require CPP and more than 90% can waive onsite inspection in the presence of Good Manufacturing Practice (GMP) certificate and/or inspection report. The paper also features the progress made in Malaysia, the Philippines, and the ASEAN (Association of South East Asian Nations) regional reliance initiative to reduce inefficiencies and duplications.
CONCLUSIONS: We have demonstrated the power of working together to enable regulatory agilities and efficiencies. APAC will continue to track the progress of all economies including India within the areas for improvement prioritized and discussed in this paper. APAC is also committed to working with key stakeholders including our NRAs in Asia to sustain and enable a new era of innovation ushered in by COVID-19 to benefit patients.
METHODS: The cross-sectional study was conducted at one hospital and 2 community pharmacies in Lahore, Pakistan, from November 2017 to July 2018, and comprised patients using calcium channel blockers. Data was collected using standardised scales to assess lower urinary tract symptoms and quality of life. Data was analysed using SPSS 22.
RESULTS: Of the 410 subjects, 315 (76.8%) were males. The overall median age was 50.84 years, IQR 19 with 126 (30.7%) aged 41-50 years. Of the total, 108 (26.3%) patients were on calcium channel blockers alone, while the rest were taking it in combination with other drugs. Prevalence of lower urinary tract symptoms was 307 (74.9%); mild 103 (25.1%), moderate 201 (49.1%) and severe 106 (25.9%). The symptoms were significantly associated with reduced quality of life (p<0.05).
Conclusion: Majority calcium channel blockers users had clinically significant lower urinary tract symptoms which significantly reduced patients' quality of life.
METHODS: We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand-searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Meta-analyses were conducted using random-effects models.
RESULTS: Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28-2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96-4.95.
CONCLUSIONS: Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade.