Pharmacist contributions to patient care and medical conditions present among recipients of Ontario primary care team pharmacist-led medication reviews: a qualitative analysis.

OBJECTIVES: Family Health Teams (FHTs) in Ontario, Canada are interdisciplinary primary healthcare practices where pharmacists engage in patient care including medication and chronic disease management. METHODS: Descriptive content analysis was used to examine qualitative responses of FHT pharmacists on their most significant contribution to a patient's medication management. KEY FINDINGS: Common roles described included medication management (70.2%), counselling and education (15.5%), monitoring and optimization (11.3%) and administration (3.1%). Chronic conditions addressed were diabetes (39.0%), cardiovascular (22.0%), pain (17.0%) and mental health (11.0%). CONCLUSIONS: While FHT pharmacists primarily view themselves as medication management experts, larger roles in counselling, education and chronic disease management are key contributions.

Treatment with apolipoprotein A1 protects mice against doxorubicin-induced cardiotoxicity in a scavenger receptor class B, type I-dependent manner.

Doxorubicin, an agent used to treat a variety of cancers, is cardiotoxic by triggering cardiomyocyte apoptosis. We previously showed that treating cultured cardiomyocytes with human high-density lipoprotein in vitro or transgenic overexpression of human apolipoprotein A1, its main structural protein, protects against doxorubicin-induced cardiomyocyte apoptosis in a manner dependent on the scavenger receptor class B type I [Durham KK, Chathely KM, Mak KC, Momen A, Thomas CT, Zhao YY, MacDonald ME, Curtis JM, Husain M, Trigatti BL. HDL protects against doxorubicin-induced cardiotoxicity in a scavenger receptor class B type 1-, phosphatidylinositol 3-kinase-, and Akt-dependent manner. Am J Physiol Heart Circ Physiol 314: H31-H44, 2018]. This was due to high-density lipoprotein-induced activation of Akt signaling in cardiomyocytes. We now demonstrate that mice lacking the scavenger receptor class B, type I exhibit increased sensitivity to doxorubicin-induced cardiomyocyte apoptosis in vivo. Cardiomyocytes expressing scavenger receptor class B, type I are protected from doxorubicin-induced apoptosis by preincubation with high-density lipoprotein isolated from wild-type mice, whereas high-density lipoprotein from scavenger receptor class B, type 1 knockout mice is less effective. Cardiomyocytes from scavenger receptor class B, type I knockout mice, however, are not protected by high-density lipoprotein in vitro, and hearts from knockout mice are more sensitive to doxorubicin in vivo. Pharmacological administration of purified apolipoprotein A1 dramatically protected wild-type mice from doxorubicin-induced cardiotoxicity and left ventricular dysfunction, whereas this protection was lost in scavenger receptor class B, type I-deficient mice. This demonstrates, at least in mice, that high-density lipoprotein therapy can confer protection against doxorubicin-induced cardiomyocyte apoptosis in a manner mediated by the scavenger receptor class B, type I. NEW & NOTEWORTHY We show that scavenger receptor class B, type I (SR-B1) mediates HDL-dependent protection against doxorubicin-induced cardiomyocyte apoptosis and that this is a property of SR-B1 in cardiomyocytes in vitro and in hearts in vivo. We also demonstrate that pharmacological treatment with apolipoprotein A1, the major HDL structural protein, protects mice against doxorubicin-induced cardiomyocyte apoptosis and left ventricular dysfunction in an SR-B1-dependent manner. This suggests that HDL-targeted pharmacological therapy may hold promise for protecting against the deleterious, cardiotoxic side effects of this commonly used chemotherapeutic drug.

Ionizing radiation affects miRNA composition in both young and old mice.

Purpose: Humans are exposed to both natural (e.g. soil, cosmic rays) and human-made radiation sources (e.g. medical devices, nuclear energy production) on a daily basis. The use of medical radiation sources such as Computed Tomography (CT) scans and X-ray has increased rapidly, especially in the treatment of older populations. Micro Ribonucleic Acids (miRNAs) are the major regulators of multiple low-dose radiation-induced biological processes through post-translational inhibition. As a result, understanding age-related changes of miRNA profiles that may compromise the population after low dose radiation exposure has become increasingly important. Materials and methods: In this study, we irradiated both young (2 months) and old (26 months) C57BL/6J mice with low dose radiation (10 mGy and 100 mGy at 1 mGy/min using an open beam 60Co gamma source) and checked the miRNA expression profiles. Results: The global miRNA expression of old mice was significantly reduced compared to that of young mice. Low dose radiation at 10 mGy significantly increased the global miRNA expression in both old and young mice one week following irradiation, which suggests that 10 mGy low dose radiation may reverse the global inhibition effects of aging on miRNA expression. Higher 100 mGy radiation slightly reduced the global expression of miRNAs. We also identified several miRNAs that were elevated or reduced in all of the radiation treatment groups; these can be further explored as candidates for the radiation-induced bio-markers. Conclusions: The results of our study demonstrate that both radiation and aging can influence the global expression of miRNAs, while low dose radiation modulates the expression of miRNAs in a dose-, time-, and age-dependent manner.

HDL protects against doxorubicin-induced cardiotoxicity in a scavenger receptor class B type 1-, PI3K-, and Akt-dependent manner.

Doxorubicin is a widely used chemotherapeutic with deleterious cardiotoxic side effects. HDL has been shown to protect cardiomyocytes in vitro against doxorubicin-induced apoptosis. Scavenger receptor class B type 1 (SR-B1), a high-affinity HDL receptor, mediates cytoprotective signaling by HDL through Akt. Here, we assessed whether increased HDL levels protect against doxorubicin-induced cardiotoxicity in vivo and in cardiomyocytes in culture and explored the intracellular signaling mechanisms involved, particularly the role of SR-B1. Transgenic mice with increased HDL levels through overexpression of human apolipoprotein A1 (apoA1Tg/Tg) and wild-type mice (apoA1+/+) with normal HDL levels were treated repeatedly with doxorubicin. After treatment, apoA1+/+ mice displayed cardiac dysfunction, as evidenced by reduced left ventricular end-systolic pressure and +dP/d t, and histological analysis revealed cardiomyocyte atrophy and increased cardiomyocyte apoptosis after doxorubicin treatment. In contrast, apoA1Tg/Tg mice were protected against doxorubicin-induced cardiac dysfunction and cardiomyocyte atrophy and apoptosis. When SR-B1 was knocked out, however, overexpression of apoA1 did not protect against doxorubicin-induced cardiotoxicity. Using primary neonatal mouse cardiomyocytes and human immortalized ventricular cardiomyocytes in combination with genetic knockout, inhibitors, or siRNA-mediated knockdown, we demonstrated that SR-B1 is required for HDL-mediated protection of cardiomyocytes against doxorubicin-induced apoptosis in vitro via a pathway involving phosphatidylinositol 3-kinase and Akt1/2. Our findings provide proof of concept that raising apoA1 to supraphysiological levels can dramatically protect against doxorubicin-induced cardiotoxicity via a pathway that is mediated by SR-B1 and involves Akt1/2 activation in cardiomyocytes. NEW & NOTEWORTHY We have identified an important role for the scavenger receptor class B type 1 in facilitating high-density lipoprotein-mediated protection of cardiomyocytes against stress-induced apoptosis and shown that increasing plasma high-density lipoprotein protects against the deleterious side effects of the chemotherapeutic and cardiotoxic drug doxorubicin.