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- 저자 : Docherty (검색결과 4 건)
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Roles for α1-adrenoceptors during contractions by electrical field stimulation in mouse vas deferens
Hadeel A. Alsufyani,James R. Docherty 대한생리학회-대한약리학회 2021 The Korean Journal of Physiology & Pharmacology Vol.25 No.6
We have investigated the relative roles of α1-adrenoceptors and purinoceptors in contractions to low and high frequency stimulation of the mouse vas deferens, in terms of the time course of responses. In separate experiments, isometric contractile responses were obtained to 10 pulses at 1 Hz and 40 pulses at 10 Hz. Responses to 1 Hz stimulation consisted of a series of discrete peaks. The α1A-adrenoceptor antagonist RS100329 (10-9M-10-7M) significantly reduced the response to the first pulse, the α1D-adrenoceptor antagonist BMY7378 (10-7M-10-6M) significantly reduced the response to the first two pulses, and the non-selective α1- adrenoceptor antagonist prazosin (10-8M) reduced the response to the first 4 pulses at 1 Hz. Responses to 10 Hz stimulation consisted of an early peak response and a maintained plateau response. RS100329 significantly reduced the peak response but did not significantly affect the plateau response. Prazosin, significantly reduced both the peak and plateau responses. The α1A-adrenoceptor antagonist RS17053 in high concentrations reduced mainly the plateau response leaving a clear early peak response. The plateau response of contraction was almost abolished by the purinoceptor antagonist suramin. These results suggest that there is a relatively minor early α1D-adrenoceptor and a larger early α1A-adrenoceptor component to stimulationevoked contractions of mouse vas deferens, but the major α1-adrenoceptor component is revealed by prazosin to be α1B-adrenoceptor mediated. α1B-Adrenoceptor activation probably facilitates contractions mediated by other α1-adrenoceptors and by purinoceptors. These results suggest that combined non-selective α1-adrenoceptor blockade, particularly α1B-adrenoceptor blockade, in addition to P2X1-purinoceptor blockade is useful in reducing male fertility
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Hadeel A. Alsufyani,James R. Docherty The Korean Society of Pharmacology 2023 The Korean Journal of Physiology & Pharmacology Vol.27 No.4
α<sub>1</sub>-adrenoceptors link via the G-protein Gq/G<sub>11</sub> to both Ca<sup>2+</sup> entry and release from stores, but may also activate Rho kinase, which causes calcium sensitization. This study aimed to identify the subtype(s) of α<sub>1</sub>-adrenoceptor involved in Rho kinase-mediated responses in both rat aorta and mouse spleen, tissues in which contractions involve multiple subtypes of α<sub>1</sub>-adrenoceptor. Tissues were contracted with cumulative concentrations of noradrenaline (NA) in 0.5 log unit increments, before and in the presence of an antagonist or vehicle. Contractions produced by NA in rat aorta are entirely α<sub>1</sub>-adrenoceptor mediated as they are competitively blocked by prazosin. The α<sub>1A</sub>-adrenoceptor antagonist RS100329 had low potency in rat aorta. The α<sub>1D</sub>-adrenoceptor antagonist BMY7378 antagonized contractions in rat aorta in a biphasic manner: low concentrations blocking α<sub>1D</sub>-adrenoceptors and high concentrations blocking α<sub>1B</sub>-adrenoceptors. The Rho kinase inhibitor fasudil (10 µM) significantly reduced aortic contractions in terms of maximum response, suggesting inhibition of α<sub>1B</sub>-adrenoceptor mediated responses. In the mouse spleen, a tissue in which all 3 subtypes of α<sub>1</sub>-adrenoceptor are involved in contractions to NA, fasudil (3 µM) significantly reduced both early and late components to the NA contraction, the early component involving α<sub>1B</sub>- and α<sub>1D</sub>-adrenoceptors, and the late component involving α<sub>1B</sub>- and α<sub>1A</sub>-adrenoceptors. This suggests that fasudil inhibits α<sub>1B</sub>-adrenoceptor mediated responses. It is concluded that α<sub>1D</sub>- and α<sub>1B</sub>-adrenoceptors interact in rat aorta and α<sub>1D</sub>-, α<sub>1A</sub>- and α<sub>1B</sub>-adrenoceptors interact in the mouse spleen to produce contractions and these interactions suggest that one of the receptors preferentially activates Rho kinase, most likely the α<sub>1B</sub>-adrenoceptor.
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Sacubitril/Valsartan in Asian Patients with Heart Failure with Reduced Ejection Fraction
Pooja Dewan,John J.V. McMurray,Kieran F. Docherty 대한심장학회 2019 Korean Circulation Journal Vol.49 No.6
The Prospective comparison of Angiotensin Receptor-neprilysin inhibitor (ARNI) with Angiotensin converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and morbidity in Heart Failure (HF) trial (PARADIGM-HF) showed that adding a neprilysin inhibitor (sacubitril) to a renin-angiotensin system blocker (and other standard therapy) reduced morbidity and mortality in ambulatory patients with chronic HF with reduced ejection fraction (HFrEF). In PARADIGM-HF, valsartan combined with sacubitril (a so-called ARNI) was superior to the current gold standard of an ACEI, specifically enalapril, reducing the risk of the primary composite outcome of cardiovascular (CV) death or first HF hospitalization by 20% and all-cause death by 16%. Following the results of PARADIGM-HF, sacubitril/valsartan was approved by American and European regulatory authorities for the treatment of HFrEF. The burden of HF in Asia is substantial, both due to the huge population of the region and as a result of increasing CV risk factors and disease. Both the prevalence and mortality associated with HF are high in Asia. In the following review, we discuss the development of sacubitril/valsartan, the prototype ARNI, and the available evidence for its efficacy and safety in Asian patients with HFrEF.
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The Effect of Bariatric Surgery on Diabetic Retinopathy: Good, Bad, or Both?
Dora M. Gorman,Carel W. le Roux,Neil G. Docherty 대한당뇨병학회 2016 Diabetes and Metabolism Journal Vol.40 No.5
Bariatric surgery, initially intended as a weight-loss procedure, is superior to standard lifestyle intervention and pharmacological therapy for type 2 diabetes in obese individuals. Intensive medical management of hyperglycemia is associated with improved microvascular outcomes. Whether or not the reduction in hyperglycemia observed after bariatric surgery translates to improved microvascular outcomes is yet to be determined. There is substantial heterogeneity in the data relating to the impact of bariatric surgery on diabetic retinopathy (DR), the most common microvascular complication of diabetes. This review aims to collate the recent data on retinal outcomes after bariatric surgery. This comprehensive evaluation revealed that the majority of DR cases remain stable after surgery. However, risk of progression of pre-existing DR and the development of new DR is not eliminated by surgery. Instances of regression of DR are also noted. Potential risk factors for deterioration include severity of DR at the time of surgery and the magnitude of glycated hemoglobin reduction. Concerns also exist over the detrimental effects of postprandial hypoglycemia after surgery. In vivo studies evaluating the chronology of DR development and the impact of bariatric surgery could provide clarity on the situation. For now, however, the effect of bariatric surgery on DR remains inconclusive.
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