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排序方式: 共有667条查询结果,搜索用时 15 毫秒
661.
SL Able RL Fish H Bye L Booth YR Logan C Nathaniel P Hayter SD Katugampola 《British journal of pharmacology》2011,162(2):405-414
BACKGROUND AND PURPOSE
The P2X7 receptor is implicated in inflammation and pain and is therefore a potential target for therapeutic intervention. Here, the development of a native tissue radioligand binding, localization and ex vivo occupancy assay for centrally penetrant P2X7 receptor antagonists is described.EXPERIMENTAL APPROACH
Autoradiography studies using the P2X7 antagonist radioligand [3H]-A-804598 were carried out in rat brain and spinal cord. Subsequent in vitro binding and ex vivo occupancy assays were performed using rat cortex homogenate.KEY RESULTS
P2X7 expression was shown to be widespread throughout the rat brain, and in the grey matter of the spinal cord. In binding assays in rat cortex homogenate, ∼60% specific binding was achieved at equilibrium. In kinetic binding assays, kon and koff values of 0.0021·min−1·nM−1 and 0.0070·min−1 were determined, and the Kd derived from kinetic measurements was consistent with that derived from saturation analysis. Novel P2X7 antagonists inhibited the binding of [3H]-A-804598 to rat cortex P2X7 receptors with Ki values of <40 nM. In an ex vivo occupancy assay, a P2X7 antagonist dosed orally to rats caused a concentration-dependent inhibition of the specific binding of [3H]-A-804598 to rat cortex.CONCLUSIONS AND IMPLICATIONS
The present study describes the development of an assay that allows localization of P2X7 receptors, the measurement of the binding affinity of P2X7 receptor antagonists in native tissue, and provides a means of determining central P2X7 receptor occupancy. These assays could form an important part of a P2X7 drug discovery programme. 相似文献662.
663.
The global prevalence of non‐alcoholic fatty liver disease (NAFLD) is rising, along with the epidemic of diabesity. NAFLD is present in >70% of individuals with type 2 diabetes. Although the mutually detrimental relationship between NAFLD and type 2 diabetes has been well established, a multitude of recent studies have further shown that type 2 diabetes is closely linked to the development of cirrhosis, hepatocellular carcinoma, liver‐related morbidity and mortality. In contrast, NAFLD also negatively impacts type 2 diabetes both in terms of its incidence and related adverse clinical outcomes, including cardiovascular and chronic kidney diseases. In response to these global health threats, clinical care pathways for NAFLD and guidelines for metabolic dysfunction‐associated fatty liver disease have been developed. Several antidiabetic agents have been evaluated for their potential hepatic benefits with promising results. Furthermore, type 2 diabetes patients are increasingly represented in clinical trials of novel therapeutics for NAFLD. However, despite the wealth of knowledge in NAFLD and type 2 diabetes, lack of awareness of the disease and the potential weight of this problem remains a major challenge, especially among clinicians who are outside the field of hepatology and gastroenterology. This review therefore aimed to provide all diabetes care providers with a summary of the latest evidence that supports NAFLD as an emerging diabetic complication of increasing importance, and to present the current recommendations, focusing on the assessment and therapeutic strategies, on the management of NAFLD among type 2 diabetes patients. 相似文献
664.
Nathan M Kerr Hussain Y Patel Shenton SL Chew Noor Q Ali Elizabeth K Eady Helen V Danesh‐Meyer 《Clinical & experimental ophthalmology》2013,41(1):27-35
Background: The aim of this study is to assess patient satisfaction, convenience of use, ease of administration, side effects and treatment burden of topical ocular hypotensives. Design: Prospective, observational cohort. Participants: Two thousand five hundred and forty‐one patients with glaucoma or ocular hypertension. Methods: The Treatment Impact Patient Satisfaction Scale (TIPSS) was administered by mail to all patients with glaucoma or ocular hypertension registered with Glaucoma New Zealand during a 3‐month study period. The questionnaire assessed patient demographics; topical ocular hypotensive use including number of medications, frequency of administration, ease of use, class of medication, and presence/severity of side effects; impact on quality of life; and patient satisfaction. Univariate and multivariate analyses were performed to identify determinants of patient satisfaction. Main Outcome Measures: Patient satisfaction. Results: Almost 80% of respondents were either ‘very satisfied’ or ‘satisfied’ with topical ocular hypotensives. Factors that were predictive of patient satisfaction included satisfaction with frequency of eye drop use {odds ratio (OR) 2.4 (95% confidence interval [CI] 1.8–3.1); P < 0.001}, subjective convenience (OR 2.6 [95% CI 2.0–3.4]; P < 0.001) and ease of administration (OR 2.5 [95% CI 2.0–3.3]; P < 0.001). Male gender was associated with lower satisfaction (OR 0.6 [95% CI 0.5–0.9]; P = 0.01). Factors that were not predictive of patient satisfaction included age, duration of eye drop use, class of medication and the presence of side effects. Conclusions: Patients with glaucoma and ocular hypotension are satisfied with topical ocular hypotensives. Efforts to improve patient satisfaction should focus on convenience and ease of administration. 相似文献
665.
Itziar Mendez-Pinto RN MSN PhD student Maria Antuña-Casal RN MSN PhD student Maria-Pilar Mosteiro-Diaz RN PhD SL 《International journal of mental health nursing》2023,32(2):479-489
The COVID-19 pandemic had a notable impact on the psychological well-being of a large part of the population, putting them at risk of developing depressive symptoms, different levels of anxiety disorders, and posttraumatic stress disorder (PTSD). One group considered to be at high risk are Nursing students; they were affected as learning strategies changed and clinical practices were cancelled. This study attempts to assess the psychological impact COVID-19 pandemic had on Nursing students and to explore the sociodemographic differences that can be risk factors for mental health disturbance. The psychological impact was evaluated using the Impact of Event Scale-Revised (IES-R) and Hospital Anxiety and Depression Scale (HADS). The study took place 4 months after the state of alarm was declared over in Spain. From a total sample of 304 Nursing students, 26.7%, 39.8%, and 15.5% showed PTSD, anxiety, and depression symptoms, respectively. Severe levels of psychological impact have been associated with being a female, a smoker, and feeling fear and stress. Having a relative test positive has been linked to lower anxiety levels while being afraid or stressed to higher anxiety levels. Being a female, co-habit with friends and feeling stress have been associated with higher depression levels. 相似文献
666.
Fabian SL Yii 《Ophthalmic & physiological optics》2023,43(6):1412-1418
Purpose
To compare axial length (AL) growth curves in East Asian (EA) and non-EA emmetropes.Methods
A meta-regression of 28 studies with emmetrope-specific AL data (measured with optical biometry) was performed. Emmetropia was defined as spherical equivalent refraction (SER) between −0.50 and +1.25 D, determined under cycloplegia if the mean age was ≤20 years. The AL growth curve (mean AL vs. mean age) was first fitted to the full dataset using a weighted nonlinear mixed-effects model, before refitting the model with ethnicity as a two-level grouping variable (EA vs. non-EA). Ethnic differences in growth curve parameters were tested using the Wald test.Results
A total of 3331 EA and 1071 non-EA emmetropes (mean age: 6.5–23.1 years) were included. There was no evidence of an ethnic difference in either final AL (difference: 0.15 mm, 95% CI: −0.04 to 0.35 mm, p = 0.15) or initial AL, as represented by the amount that the final AL needed to be offset to obtain the y-intercept (difference: −2.77 mm, 95% CI: −10.97 to 5.44, p = 0.51). Likewise, AL growth rate (curve steepness) did not differ between ethnic groups (difference: 0.09, 95% CI: −0.13 to 0.31, p = 0.43). Collectively, AL growth rate decreased from 0.24 mm/year at 6 years of age to around 0.05 mm/year at 11 years of age, after which it dipped below the repeatability of optical biometry (±0.04 mm) and practically plateaued around 16 years of age (final AL: 23.60 mm).Conclusions
EA and non-EA emmetropes have comparable AL growth curves. 相似文献667.