PURPOSE: As deaths from the illicit drug poisoning crisis continue to rise in Canada, increasing the number of healthcare professionals qualified to effectively prescribe opioids could be beneficial. The willingness of family medicine residents to undertake structured training in prescribing opioids for Opioid Agonist Treatment (OAT) and pain management have not been well described. MATERIALS AND METHODS: Family medicine residents (n = 20) in British Columbia, Canada, were asked about their experience with and willingness to enrol in OAT training. Informed by the Consolidated Framework for Implementation Research, data were analysed thematically using NVivo software. RESULTS: Four themes were identified: (1) challenges to training implementation, (2) feelings and attitudes on prescribing practices, (3) helpful learning spaces and places of substance use training, and (4) recommendations for implementing training. Preparedness, exposure, and supportive learning environments for substance use education increased willingness to pursue OAT accreditation, while ineffective learning experiences, mixed feelings about opioid prescribing, and lack of protected time were the most common reasons for unwillingness. CONCLUSIONS: Protected time and a range of clinical experiences appear to facilitate residents' willingness to complete OAT and opioid training. Implementation strategies to enhance the uptake of OAT accreditation in family medicine residency must be prioritised.
- MeSH
- lékařská praxe - způsoby provádění MeSH
- lidé MeSH
- opioidní analgetika * terapeutické užití MeSH
- poruchy spojené s užíváním psychoaktivních látek * farmakoterapie MeSH
- rodinné lékařství MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Kanada MeSH
Cardiac muscle-related microRNAs play important roles in cardiac development and disease by translational silencing of mRNAs, the dominant mechanism of microRNA action. To test whether they could be involved in daunorubicin-associated cardiomyopathy (DACM), we determined expression patterns of myomiRs in two distinct models of DACM. We used 10-12 weeks old male Wistar rats. In the sub-acute model, rats were administered with six doses of daunorubicin (DAU-A, 3 mg/kg, i.p., every 48 h). Rats were sacrificed two days after the last dose. In the sub-chronic model, anaesthetized rats were administered a single dose of daunorubicin (15 mg/kg, i.v., DAU-C). Age-matched controls (CON) received vehicle. Rats were sacrificed eight weeks later. Left ventricular (LV) functions (LV pressure, rate of pressure development, +dP/dt and decline, -dP/dt) were measured using left ventricular catheterization. Expressions of myomiRs (miR-208a, miR-499, miR-1 and miR-133a), markers of cardiac failure (atrial and brain natriuretic peptides genes; Nppa and Nppb) and myosin heavy chain genes (Myh6, Myh7, Myh7b) in cardiac tissue were determined by RT-PCR. Protein expression of gp91phox NADPH oxidase subunit was detected by immunoblotting. Both DAU groups exhibited a similar depression of LV function, and LV weight reduction, accompanied by an upregulation of natriuretic peptides, and a decrease of Myh6 to total Myh ratio (-18% in DAU-A and - 25% in DAU-C, as compared to controls; both P < 0.05). DAU-C, but not DAU-A rats had a 35% mortality rate and exhibited a significantly increased gp91phox expression (DAU-C: 197 ± 33 versus CON-C: 100 ± 11; P < 0.05). Interestingly, myomiRs levels were only reduced in DAU-C compared to CON-C (miR-208: -45%, miR-499: -30%, miR-1: -29%, miR- and miR133a: -25%; all P < 0.05) but were unaltered in DAU-A. The lack of myomiRs expression, particularly in sub-chronic model, suggests the loss of control of myomiRs network on late progression of DACM. We suppose that the poor inhibition of mRNA targets might contribute to chronic DACM.
- MeSH
- daunomycin škodlivé účinky farmakologie MeSH
- down regulace účinky léků MeSH
- kardiomyopatie chemicky indukované metabolismus patologie patofyziologie MeSH
- krysa rodu rattus MeSH
- mikro RNA biosyntéza MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- svalové proteiny biosyntéza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains "Which dose is safe?", as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistical power. This review will focus on comprehensive and critical review of the current literature and provide an avenue for further study.
- MeSH
- cévy účinky léků metabolismus MeSH
- kardiovaskulární nemoci epidemiologie MeSH
- káva škodlivé účinky chemie MeSH
- klinická studie jako téma MeSH
- kofein aplikace a dávkování škodlivé účinky MeSH
- lidé MeSH
- metaanalýza jako téma MeSH
- metabolický syndrom epidemiologie MeSH
- modely nemocí na zvířatech MeSH
- srdce účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
UNLABELLED: Chronic heart failure (CHF) remains a leading cause of cardiovascular death worldwide. Current risk models allow better prognosis, however further tools for assessing risk are needed. Thus, this study was aimed to evaluate whether biomarker risk prediction score is powerful tool for risk assessment of three-year fatal and non-fatal cardiovascular events in CHF patients. METHODS: A prospective study on the incidence of fatal and non-fatal cardiovascular events, as well as the frequency of occurrence of death from any cause in a cohort of 388 patients with CHF during 3 years of observation was performed. Circulating levels of NT-pro brain natriuretic peptide (NT-pro-BNP), galectin-3, high-sensitivity C-reactive protein (hs-CRP), osteoprotegerin and its soluble receptor sRANKL, osteopontin, osteonectin, adiponectin, endothelial apoptotic microparticles (EMPs) and mononuclear progenitor cells (MPCs) were measured at baseline. RESULTS: Median follow-up of patients included in the study was 2.76 years. There were 285 cardiovascular events determined, including 43 deaths and 242 readmissions. Independent predictors of clinical outcomes in patients with CHF were NT-pro-BNP, galectin-3, hs-CRP, osteoprotegerin, CD31(+)/annexin V(+) EMPs and EMPs/CD14(+)CD309(+) MPCs ratio. Index of cardiovascular risk was calculated by mathematical summation of all ranks of independent predictors, which occurred in the patients included in the study. The findings showed that the average value of the index of cardiovascular risk in patients with CHF was 3.17 points (95% CI = 1.65-5.10 points). Kaplan-Meier analysis showed that patients with CHF and the magnitude of the risk of less than 4 units have an advantage in survival when compared with patients for whom obtained higher values of ranks cardiovascular risk score. CONCLUSION: Biomarker risk score for cumulative cardiovascular events, constructed by measurement of circulating NT-pro-BNP, galectin-3, hs-CRP, osteoprotegerin, CD31(+)/annexin V(+) EMPs and EMPs/CD14(+)CD309(+) MPCs ratio, reliably predicts the probability survival of patients with CHF, regardless of age, gender, state of the contractile function of the left ventricle and the number of comorbidities.
- Publikační typ
- časopisecké články MeSH
The role of an atherogenic diet in causing pulmonary fibrosis has received little attention and simvastatin has been shown to reduce pulmonary fibrosis in animal models. To determine if an atherogenic diet can induce pulmonary fibrosis and whether simvastatin treatment is beneficial by up-regulating heat shock protein 70 and 90. New Zealand white rabbits (n = 15) were divided: Group 1 (control); Group 2 (MC) received a normal rabbit diet with 1% methionine plus 0.5% cholesterol (atherogenic diet). Group 3 received the same diet as the MC group plus 5 mg/kg/day simvastatin orally (MCS). After 4 weeks, the lungs were collected and analysed. Picrosirus red staining of lung interstitial collagen content showed that the atherogenic diet increased fibrosis 2.9-fold (P < 0.05), bronchiole adventitial collagen was increased 2.3-fold (P < 0.05) and bronchiole epithelium was increased 34-fold (P < 0.05), and simvastatin treatment severely reduced this effect (P < 0.05). Western blot analysis showed that the atherogenic diet significantly reduced lung Hsp70 protein by 22% (P < 0.05) and Hsp90 protein by 18% (P < 0.05) and simvastatin treatment did not affect this result. However, aortic hyper-responsiveness to vasoconstrictors (angiotensin II and phenylephrine) were markedly reduced by simvastatin treatment. We report that an atherogenic diet stimulates pulmonary fibrosis and reduces lung Hsp70/Hsp90 protein concentration. Simvastatin impairs this by mechanisms unrelated to Hsp70/Hsp90, but possibly a reduction in angiotensin II receptor or alpha adrenergic receptor pathways. These results could have implications in idiopathic pulmonary fibrosis.
- MeSH
- anticholesteremika terapeutické užití MeSH
- dieta aterogenní škodlivé účinky MeSH
- králíci MeSH
- plíce metabolismus patologie MeSH
- plicní fibróza farmakoterapie etiologie metabolismus prevence a kontrola MeSH
- proteiny tepelného šoku HSP70 metabolismus MeSH
- proteiny tepelného šoku HSP90 metabolismus MeSH
- receptory angiotensinu metabolismus MeSH
- simvastatin terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Calcium release channel on the sarcoplasmic reticulum of cardiomyocytes (ryanodine receptor type 2, RyR2) plays a critical role in the regulation of calcium and was identified as a crucial factor for development of chronic anthracycline cardiomyopathy. Its early stages are less well described although these determine the later development. Hence, we tested the effect of repeated, short-term anthracycline (daunorubicin) administration on cardiac performance, cardiomyocyte function and accompanied changes in calcium regulating proteins expression. Ten-twelve weeks old male Wistar rats were administered with 6 doses of daunorubicin (DAU, 3 mg/kg, i.p., every 48 h), controls (CON) received vehicle. Left ventricular function (left ventricular pressure, LVP; rate of pressure development, +dP/dt and decline, -dP/dt) was measured using left ventricular catheterization under tribromethanol anaesthesia (15 ml/kg b.w.). Cell shortening was measured in enzymatically isolated cardiomyocytes. The expressions of RyR2 and associated intracellular calcium regulating proteins, cytoskeletal proteins (alpha-actinin, alpha-tubul in) as well as oxidative stress regulating enzymes (gp91phox, MnSOD) were detected in ventricular tissue samples using immunoblotting. mRNA expressions of cardiac damage markers (Nppa and Nppb, atrial and brain natriuretic peptides; Myh6, Myh7 and Myh7b, myosin heavy chain alpha and beta) were detected using RT-PCR. Thiobarbituric acid reactive substances concentration was measured to estimate oxidative stress. DAU rats exhibited significantly depressed left ventricular features (LVP by 14%, +dP/dt by 36% and -dP/dt by 30%; for all P<0.05), in line with concomitant increase in Nppa and Nppb gene expressions (3.23- and 2.18-fold, for both P<0.05), and a 4.34-fold increase in Myh7 (P<0.05). Controversially, we observed increased cell shortening of isolated cardiac cells by 31% (p<0.05). DAU administration was associated with a twofold upregulation of RyR2 (P<0.05), but not of other examined Ca(2+) regulating proteins remained. In addition, we observed a significant reduction in alpha-tubulin (by 46% when compared to CON P<0.05). Indicators of oxidative injury were unaffected. In conclusion, unbalanced RyR2 overexpression plays a particular role in early development of daunorubicin cardiomyopathy characterized by discrepant in situ versus in vitro cardiac performance.
- Publikační typ
- časopisecké články MeSH
The duration of the QT interval as measured by 12-lead electrocardiography is a measure of myocardial repolarization and is widely used to describe cardiac abnormalities, to determine the presence of cardiac toxicity and to evaluate drug safety. In hypertension, the QT interval is a predictor of the risk of both coronary events and cardiovascular death, after adjusting for the effects of additional risk factors. The mechanism of QT interval prolongation is multifactorial and includes cardiomyocyte hypertrophy and increased left ventricular mass, with accompanying changes in left ventricular transmural dispersion of repolarization, as well as changes in the tone of the autonomic nervous system of some patients with hypertension and mechano-electrical feedback, although this mechanism is less likely. Antihypertensive drugs vary in their effect on QT interval duration. The mechanisms underlying their effect depend on changes in left ventricular mass and autonomic nervous system tone, as well as changes in the activity of cardiac ion channels. Although blood pressure reduction is the primary goal of antihypertensive drug therapy and although the choice of antihypertensive drug treatment regimens varies among different individuals, the data regarding the disparate effects of antihypertensive drugs on the duration of the QT interval warrant consideration when implementing long-term pharmacotherapy for hypertension.
- MeSH
- antihypertenziva terapeutické užití MeSH
- elektrokardiografie účinky léků MeSH
- hypertenze diagnóza farmakoterapie patofyziologie MeSH
- hypertrofie levé komory srdeční farmakoterapie patofyziologie MeSH
- lidé MeSH
- srdeční frekvence účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Since the identification of the alternative angiotensin converting enzyme (ACE)2/Ang-(1-7)/Mas receptor axis, renin-angiotensin system (RAS) is a new complex target for a pharmacological intervention. We investigated the expression of RAS components in the heart and kidney during the development of hypertension and its perinatal treatment with losartan in young spontaneously hypertensive rats (SHR). Expressions of RAS genes were studied by the RT-PCR in the left ventricle and kidney of rats: normotensive Wistar, untreated SHR, SHR treated with losartan since perinatal period until week 9 of age (20 mg/kg/day) and SHR treated with losartan only until week 4 of age and discontinued until week 9. In the hypertrophied left ventricle of SHR, cardiac expressions of Ace and Mas were decreased while those of AT1 receptor (Agtr1a) and Ace2 were unchanged. Continuous losartan administration reduced LV weight (0.43 ± 0.02; P < 0.05 versus SHR) but did not influence altered cardiac RAS expression. Increased blood pressure in SHR (149 ± 2 in SHR versus 109 ± 2 mmHg in Wistar; P < 0.05) was associated with a lower renal expressions of renin, Agtr1a and Mas and with an increase in ACE2. Continuous losartan administration lowered blood pressure to control levels (105 ± 3 mmHg; P < 0.05 versus SHR), however, only renal renin and ACE2 were significantly up-regulated (for both P < 0.05 versus SHR). Conclusively, prevention of hypertension and LV hypertrophy development by losartan was unrelated to cardiac or renal expression of Mas. Increased renal Ace2, and its further increase by losartan suggests the influence of locally generated Ang-(1-7) in organ response to the developing hypertension in SHRs.
- MeSH
- angiotensin konvertující enzym metabolismus MeSH
- hypertenze komplikace farmakoterapie genetika prevence a kontrola MeSH
- hypertrofie levé komory srdeční komplikace farmakoterapie genetika prevence a kontrola MeSH
- ledviny účinky léků enzymologie MeSH
- losartan aplikace a dávkování farmakologie terapeutické užití MeSH
- messenger RNA genetika metabolismus MeSH
- myokard enzymologie MeSH
- novorozená zvířata MeSH
- oxid dusnatý metabolismus MeSH
- potkani inbrední SHR MeSH
- protoonkogenní proteiny metabolismus MeSH
- receptory spřažené s G-proteiny metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- renin-angiotensin systém účinky léků genetika MeSH
- signální transdukce účinky léků MeSH
- srdeční komory účinky léků metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
