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Background– This study intends to address the scarcity of data regarding the pathogenesis of Baclofen poisoning in humans, which has seen a recent increase, worldwide, especially amongst the young people. Another reason for the conduction of this study was lack of the substantial data about the histo-pathological findings of lungs, in synergistic toxicity of Baclofen with Ethanol, in-spite of it being very common in humans, and both being respiratory depressant with similar mechanism of action.Purpose– The authors aimed to understand the pathogenesis of fatal poisonings in humans due to Baclofen in combination with Ethanol via an animal research model. The enhancement of the overall scientific literature by extending research along the lines of the handful studies available in this regard was another adjunct goal of the study.Material and methodsFifteen Wistar rats were divided into control and test group of five and ten subjects respectively. The test group was further divided into two sub-groups of five each, with Baclofen administered to one, and it in conjunction with Ethanol to the other, in lowest dosages adjusted for the humans. Rats in both the groups were euthanized by dislocation of the cervical vertebrae for the histopathology examination.ResultsCapillary and venous plethora, hemorrhages in the inter-alveolar septi, hemorrhages into the alveoli and sludging was seen in the 1st sub-group. The plethora of venules, capillaries and arterioles, with sludging by the WBC (white blood corpuscle) infiltrates was seen in the 2nd sub-group. Desquamation of the ciliated epithelium and edematous thickening of the intra-alveolar septi, along with features suggestive of the peri-vascular edema was seen in the 2nd sub-group. The morphometric analysis of the micro vessels showed a significantly higher value of the arteriolar diameter in the 2nd sub-group, in comparison to 1st, but the venular diameter in the two sub-groups did not differ to any extent.  相似文献   
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《Drug discovery today》2022,27(1):280-291
Positron emission tomography (PET) is an extensively used nuclear functional imaging technique, especially for central nervous system (CNS) and oncological disorders. Currently, drug development is a lengthy and costly pursuit. Imaging with PET radiotracers could be an effective way to hasten drug discovery and advancement, because it facilitates the monitoring of key facets, such as receptor occupancy quantification, drug biodistribution, pharmacokinetic (PK) analyses, validation of target engagement, treatment monitoring, and measurement of neurotransmitter concentrations. These parameters demand careful analyses for the robust appraisal of newly formulated drugs during preclinical and clinical trials. In this review, we discuss the usage of PET imaging in radiopharmaceutical development; drug development approaches with PET imaging; and PET developments in oncological and cardiac drug discovery.  相似文献   
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BackgroundAdverse drug reactions (ADRs) and adverse drug events (ADEs) in older people contribute to a significant proportion of hospital admissions and are common following discharge. Effective interventions are therefore required to combat the growing burden of preventable ADRs. The Prediction of Hospitalisation due to Adverse Drug Reactions in Elderly Community Dwelling Patients (PADR-EC) score is a validated risk score developed to assess the risk of ADRs in people aged 65 years and older and has the potential to be utilised as part of an intervention to reduce ADRs.ObjectivesThis trial was designed to investigate the effectiveness of an intervention to reduce ADR incidence in older people and to obtain further information about ADRs and ADEs in the 12–24 months following hospital discharge.MethodsThe study is an open-label randomised-controlled trial to be conducted at the Royal Hobart Hospital, a 500-bed public hospital in Tasmania, Australia. Community-dwelling patients aged 65 years and older with an unplanned overnight admission to a general medical ward will be recruited. Following admission, the PADR-EC ADR score will be calculated by a research pharmacist, with the risk communicated to clinicians and discussed with participants. Following discharge, nominated general practitioners and community pharmacists will receive the risk score and related medication management advice to guide their ongoing care of the patient. Follow-up with participants will occur at 3 and 12 and 18 and 24 months to identify ADRs and ADEs. The primary outcome is moderate-severe ADRs at 12 months post-discharge, and will be analysed using the cumulative incidence proportion, survival analysis and Poisson regression.SummaryIt is hypothesised that the trial will reduce ADRs and ADEs in the intervention population. The study will also provide valuable data on post-discharge ADRs and ADEs up to 24 months post-discharge.  相似文献   
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Valproic acid (VPA) is an anti-seizure drug that causes idiosyncratic liver injury. 2-propyl-4-pentenoic acid (Δ4VPA), a metabolite of VPA, has been implicated in VPA-induced hepatotoxicity. This review summarizes the pathogenesis involved in VPA-induced liver injury. The VPA induce liver injury mainly by i) liberation of Δ4VPA metabolites; ii) decrease in glutathione stores and antioxidants, resulting in oxidative stress; iii) inhibition of fatty acid β-oxidation, inducing mitochondrial DNA depletion and hypermethylation; a decrease in proton leak; oxidative phosphorylation impairment and ATP synthesis decrease; iv) induction of fatty liver via inhibition of carnitine palmitoyltransferase I, enhancing nuclear receptor peroxisome proliferator-activated receptor-gamma and acyl-CoA thioesterase 1, and inducing long-chain fatty acid uptake and triglyceride synthesis. VPA administration aggravates liver injury in individuals with metabolic syndromes. Therapeutic drug monitoring, routine serum levels of transaminases, ammonia, and lipid parameters during VPA therapy may thus be beneficial in improving the safety profile or preventing the progression of DILI.  相似文献   
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目的 分析某医院手术室患者多重耐药菌(MDRO)感染现状,找出相关因素。方法 选择2020年2月至2021年1月泸州某医院手术室12 619例成年患者作为研究对象,调查患者资料,进行病原菌检测和细菌药敏试验,统计手术室MDRO感染发生情况,分析MDRO感染的菌种、科室分布、耐药情况和MDRO感染发生的相关因素。结果 医院手术室患者MDRO感染发生率为2.10%。MDRO感染占比较大的科室是普外科(34.28%)、骨科(23.78%)、泌尿外科(15.22%)。手术室患者MDRO感染中较常见的菌种是鲍曼不动杆菌(46.99%)、金黄色葡萄球菌(19.91%)、铜绿假单胞菌(12.04%)。鲍曼不动杆菌对头孢曲松完全耐药,对氨苄青霉素、环丙沙星、头孢他啶、头孢吡肟、庆大霉素、妥布霉素耐药率超过80.00%,仅对左氧氟沙星耐药率不超过30.00%;金黄色葡萄球菌对青霉素、苯唑西林完全耐药,对红霉素、氯林可霉素的耐药率超过80.00%;铜绿假单胞菌对头孢曲松、氨苄青霉素完全耐药,对头孢他啶、环丙沙星、复方新诺明耐药率超过80.00%,仅对阿米卡星耐药率不超过30.00%。Logistic回归分析结果显示,入住ICU(OR=5.943)、侵入性操作(OR=2.704)、抗菌药物使用时间长(OR=2.244)、合并糖尿病(OR=1.955)是医院手术室患者MDRO感染的影响因素。结论 泸州某医院手术室患者MDRO感染发生率较高,可能受入住ICU、侵入性操作、抗菌药物使用时间长、合并糖尿病的影响。  相似文献   
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BackgroundIdentifying the MIC wild-type distribution and its delineation of species targeted for receiving antimicrobial agent breakpoints is an important first step for determining clinical breakpoints. Having the main responsibility in the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for characterizing the wild-type distributions and setting epidemiological cut-off values (ECOFFs), we explain the why, the how, and frequent misconceptions of wild-type MIC distributions and ECOFFs.ObjectivesTo clarify how wild-type MIC distributions and ECOFFs for agents and important target organisms are defined and determined and why these are important tools in microbiology, as well as to point to common misunderstandings and inappropriate use.SourcesThe EUCAST database of >40 000 MIC distributions; publications addressing the definition of wild-type MIC distributions, and ECOFFs in bacteria and fungi; and the EUCAST Standard Operating Procedure 10 Documents published by the European Centre for Disease Control and the European Food Safety Agency.ContentThe rationale for defining wild-type distributions and ECOFFs is explained. Setting breakpoints that bisect wild-type MIC distributions leads to poor methodological reproducibility and poor correlation between clinical outcome and susceptibility testing results. The methods applied by EUCAST to select distributions for aggregation and website display are described, highlighting the importance of incorporating data from multiple sources and methods. The methods used by EUCAST to estimate ECOFFs are outlined. Finally, the common misunderstandings of these processes are addressed.ImplicationsThe international community needs to agree on the phenotypic definitions of wild-type distributions. Systematic methods for developing and applying ECOFFs are essential to the conduct of phenotypic antimicrobial susceptibility testing and interpretation, which will remain the dominant laboratory method for the foreseeable future.  相似文献   
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