Factors affecting prescription of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes mellitus with established cardiovascular disease/ chronic kidney disease in Hong Kong: a qualitative study.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2 I) has cardiorenal protective properties and are recommended for patients with diabetes and established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). Although cardiorenal complications are high in diabetes and pose a significant financial burden on the Hong Kong health care system, the use of SGLT2 I in these populations remains low. And yet this issue has not been explored in Hong Kong primary care. This study aimed to explore factors affecting primary care doctors' prescribing of SGLT2 I in patients with diabetes and established ASCVD/CKD in Hong Kong. METHODS: A phenomenological qualitative research using semi-structured interviews was conducted between January and May 2021 in one Hospital Authority cluster in Hong Kong. Purposive sampling was employed to recruit primary care doctors in the cluster. The Theoretical Domains Framework (TDF) underpinned the study and guided the development of the interview questions. Data was analysed using both inductive and deductive approaches. The Consolidated criteria for reporting qualitative research (COREQ) checklist was used to guide the reporting. RESULTS: Interviews were conducted with 17 primary care doctors. Four overarching themes were inductively identified: knowledge and previous practice patterns influence prescription, balancing risks and benefits, doctors' professional responsibilities, and system barriers. The four themes were then deductively mapped to the nine specific domains of the TDF: knowledge; intention; memory; beliefs about capabilities; beliefs about consequences; goals; role and identity; emotion; and environmental constraints. Most interviewees, to varying extent, were aware of the cardio-renal advantages and safety profile of SGLT2 I but are reluctant to prescribe or change their patients to SGLT2 I because of their knowledge gap that the cardio-renal benefits of SGLT2 I was independent of glyacemic efficacy. Other barriers included their considerations of patients' age and renal impairment, and patients' perceptions and preferences. CONCLUSIONS: Despite evidence-based recommendations of the utilisation of SGLT2 I in patients with established ASCVD/CKD, the prescription behaviour among primary care doctors was affected by various factors, most of which were amendable. Our findings will inform the development of structured interventions to address these factors to improve patients' cardio-renal outcomes.

Inhibition of TRPM7 channels reduces degranulation and release of cytokines in rat bone marrow-derived mast cells.

BACKGROUND: mast cells play an important role in airway inflammation in asthma. The transient receptor potential melastatin-like 7 (TRPM7) channel is expressed in primary human lung mast cells and plays a critical role for cell survival. This study aimed to investigate the role of TRPM7 on degranulation and release of cytokines in rat bone marrow-derived mast cells (BMMCs). METHODS: the expression levels of TRPM7 were observed by immunocytochemistry and RT-PCR between normal and asthmatic rat BMMCs. TRPM7-specific shRNA and 2-aminoethoxydiphenyl borate (2-APB) and specific shTRPM7 were used to inhibit the function of TRPM7. Degranulation levels were analyzed by beta-hexosaminidase assay. Histamine, TNF-α, IL-6 and IL-13 levels were measured by ELISA. RESULTS: the expression of TRPM7 was significantly higher in asthmatic rat BMMCs than in the normal control group. After application of 2-APB and down-regulation of TRPM7, the beta-hexosaminidase activity and secretion of histamine, IL-6, IL-13 and TNF-α were significantly decreased in the asthmatic group compared to the control group. CONCLUSION: this study indicates that TRPM7 channels may be involved in the process of degranulation and release of cytokines in rat bone marrow-derived mast cells.

2-Aminoethoxydiphenyl borate reduces degranulation and release of cytokines in a rat mast cell line.

BACKGROUND AND OBJECTIVE: 2-aminoethoxydiphenyl borate (2-APB) has been reported to be a useful pharmacological tool in the study of calcium signaling. It is used either as a membrane-permeable inhibitor for inositol 1,4,5-trisphosphate (IP3) receptors or a store-operated calcium (Ca2+) entry (SOCE) inhibitor. The present study aimed to evaluate the effects of 2-APB on degranulation and cytokine production after antigen activation in a rat mast cell line, RBL-2H3 cells. MATERIALS AND METHODS: Degranulation levels were analyzed by beta-hexosaminidase assay. Intracellular calcium concentrations were measured by Fluo-3 assay. The mRNA expression of interleukin-4 (IL-4) and tumor necrosis factor (TNF)-alfa were analyzed by Real-time PCR. RESULTS: The intracellular Ca2+ levels were greatly suppressed in the absence or presence of 2 mmol/L Ca2+ in the extracellular medium when RBL-2H3 cells were pretreated with 100 micromol/L 2-APB for 15 min. The beta-hexosaminidase activity as well as the mRNA expression of IL-4 and TNF-alfa levels were significantly decreased after application of 2-APB. CONCLUSION: This study indicates that the application of 2-APB may be a useful method to inhibit mast cell activation.