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排序方式: 共有2067条查询结果,搜索用时 62 毫秒
81.
Subha Dahal Ran Cheng Peter K. Cheung Terek Been Ramy Malty Melissa Geng Sarah Manianis Lulzim Shkreta Shahrazad Jahanshahi Johanne Toutant Rose Chan Sean Park Mark A. Brockman Mohan Babu Samira Mubareka Karen Mossman Arinjay Banerjee Scott Gray-Owen Martha Brown Walid A. Houry Benoit Chabot David Grierson Alan Cochrane 《Viruses》2022,14(1)
Medicinal chemistry optimization of a previously described stilbene inhibitor of HIV-1, 5350150 (2-(2-(5-nitro-2-thienyl)vinyl)quinoline), led to the identification of the thiazole-5-carboxamide derivative (GPS491), which retained potent anti-HIV-1 activity with reduced toxicity. In this report, we demonstrate that the block of HIV-1 replication by GPS491 is accompanied by a drastic inhibition of viral gene expression (IC50 ~ 0.25 µM), and alterations in the production of unspliced, singly spliced, and multiply spliced HIV-1 RNAs. GPS491 also inhibited the replication of adenovirus and multiple coronaviruses. Low µM doses of GPS491 reduced adenovirus infectious yield ~1000 fold, altered virus early gene expression/viral E1A RNA processing, blocked viral DNA amplification, and inhibited late (hexon) gene expression. Loss of replication of multiple coronaviruses (229E, OC43, SARS-CoV2) upon GPS491 addition was associated with the inhibition of viral structural protein expression and the formation of virus particles. Consistent with the observed changes in viral RNA processing, GPS491 treatment induced selective alterations in the accumulation/phosphorylation/function of splicing regulatory SR proteins. Our study establishes that a compound that impacts the activity of cellular factors involved in RNA processing can prevent the replication of several viruses with minimal effect on cell viability. 相似文献
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Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis
Julio C. Fernandes Johanne Martel-Pelletier Ivan G. Otterness Arturo Lopez-Anaya Franois Mineau Ginette Tardif Jean-Pierre Pelletier 《Arthritis \u0026amp; Rheumatology》1995,38(9):1290-1303
Objective. To examine the effects of tenidap and diclofenac on osteoarthritic lesions and metalloprotease activity in experimental osteoarthritis (OA). Methods. The anterior cruciate ligament of the right stifle joint of 25 mongrel dogs was sectioned by a stab wound. Seven dogs received no treatment, 6 were treated with oral omeprazole (20 mg/day), another 6 were treated with diclofenac (0.25 mg/kg/twice daily) plus omeprazole (20 mg/day), and 6 received oral tenidap (3 mg/kg/twice daily) plus omeprazole (20 mg/day). The dogs received medication for 8 weeks; all dogs were killed at the end of this period. Eight normal dogs were used as controls. Lesions were evaluated macroscopically for the incidence and size of osteophytes and the area and grade of cartilage erosions on the condyles and plateaus, along with histologic evaluation of the severity of the cartilage lesions and synovial inflammation. Stromelysin and collagenase activities and the collagenase messenger RNA (mRNA) level were measured in cartilage and synovial membrane. Results. Compared with the untreated or omeprazole-treated OA groups, the dogs treated with tenidap exhibited significant reduction in the incidence (P < 0.001) and size (P < 0.0001) of osteophytes. Tenidap also significantly decreased the size and grade of cartilage macroscopic lesions, as well as the histologic severity of cartilage lesions on both condyles and plateaus. The histologic severity of synovial inflammatory reaction was also significantly reduced (P < 0.003) in the tenidap group. Tenidap markedly decreased stromelysin and collagenase activity in both cartilage (stromelysin P < 0.003; collagenase P < 0.01) and synovial membrane (stromelysin P < 0.003; collagenase P < 0.005). Moreover, tenidap also decreased the collagenase mRNA level in cartilage (P < 0.005) and synovial membrane (P < 0.002). Diclofenac slightly reduced the incidence and size of osteophytes and cartilage lesions, but these changes were not statistically significant. Diclofenac had no effect on the severity of synovial inflammation, metalloprotease activity, or collagenase expression. Conclusion. This study showed that tenidap had a more potent anti-osteoarthritic effect than diclofenac in this model. The effect of the drug in suppressing metalloprotease synthesis, a process known to play a major role in the pathophysiology of osteoarthritic lesions, may explain its mechanism of action. 相似文献
84.
Rokas Sainas Suzanne Zamany Andersen Katja Li Mattia Saccoccio Kevin Krempl Jakob Bruun Pedersen Jakob Kibsgaard Peter Christian Kjrgaard Vesborg Debasish Chakraborty Ib Chorkendorff 《RSC advances》2021,11(50):31487
Lithium-mediated electrochemical ammonia synthesis (LiMEAS) in non-aqueous media is a promising technique for efficient and green ammonia synthesis. Compared to the widely used Haber–Bosch process, the method reduces CO2 emissions to zero due to the application of green hydrogen. However, the non-aqueous medium encounters the alkali metal lithium and organic components at high negative potentials of electrolysis, which leads to formation of byproducts. To assess the environmental risk of this synthesis method, standardized analytical methods towards understanding of the degradation level and consequences are needed. Here we report on the implementation of an approach to analyze the liquid electrolytes after electrochemical ammonia synthesis via high-resolution gas chromatography-mass spectrometry (GCMS). To characterize the molecular species formed after electrolysis, electron ionization high-resolution mass spectrometry (EI-MS) was applied. The fragmentation patterns enabled the elucidation of the mechanisms of byproduct formation. Several organic electrolytes were analyzed and compared both qualitatively and quantitatively to ascertain molecular composition and degradation products. It was found that the organic solvent in contact with metallic electrodeposited lithium induces solvent degradation, and the extent of this decomposition to different organic molecules depends on the organic solvent used. Our results show GCMS as a suitable technique for monitoring non-aqueous electrochemical ammonia synthesis in different organic electrolytes.Lithium-mediated non-aqueous electrochemical ammonia synthesis (LiMEAS) as an efficient and green ammonia production way was studied by GCMS in different organic electrolytes to evaluate the stability of electrochemical systems. 相似文献
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Anca A. Arbune Jesper Jeppesen Isa Conradsen Philippe Ryvlin Sándor Beniczky 《Epilepsia》2020,61(Z1):S55-S60
This study aims at defining objective parameters reflecting the severity of peri-ictal autonomic changes and their relation to post-ictal generalized electroencephalography (EEG) suppression (PGES), with the view that such changes could be detected by wearable seizure detection systems and prove useful to assess the risk of sudden unexpected death in epilepsy (SUDEP). To this purpose, we assessed peri-ictal changes in heart rate variability (HRV) and correlated them with seizure duration, intensity of electromyography-based ictal muscle activity, and presence and duration of post-ictal generalized EEG suppression (PGES). We evaluated 75 motor seizures from 40 patients, including 61 generalized tonic-clonic seizures (GTCS) and 14 other major motor seizure types. For all major motor seizures, HRV measurements demonstrated a significantly decreased parasympathetic activity and increased sympathetic activity in the post-ictal period. The post-ictal increased sympathetic activity was significantly higher for GTCS as compared with non-GTCS. The degree of peri-ictal decreased parasympathetic activity and increased sympathetic activity was associated with longer PGES (>20 s), longer seizure duration, and greater intensity of ictal muscle activity. Mean post-ictal heart rate (HR) was an independent predictor of PGES duration, seizure duration, and intensity of ictal muscle contraction. Our results indicate that peri-ictal changes in HRV are potential biomarkers of major motor seizure severity. 相似文献
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Anne Nicolaisen Gitte Bruun Lauridsen Peter Haastrup Dorte Gils Hansen Dorte Ejg Jarbl 《Scandinavian journal of primary health care》2022,40(1):11
ObjectiveGeneral practice plays an important role in cancer trajectories, and cancer patients request the continuous involvement of general practice. The objective of this scoping review was to identify healthcare practices that increase the quality of care in cancer trajectories from a general practice perspective.Design, setting, and subjectsA scoping review of the literature published in Danish or English from 2010 to 2020 was conducted. Data was collected using identified keywords and indexed terms in several databases (PubMed, MEDLINE, EBSCO CINAHL, Scopus, and ProQuest), contacting key experts, searching through reference lists, and reports from selected health political, research- and interest organizations’ websites.Main outcome measuresWe identified healthcare practices in cancer trajectories that increase quality care. Identified healthcare practices were grouped into four contextual domains and allocated to defined phases in the cancer trajectory. The results are presented according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for scoping reviews (PRISMA-ScR).ResultsA total of 45 peer-reviewed and six non-peer-reviewed articles and reports were included. Quality of care increases in all phases of the cancer trajectory when GPs listen carefully to the full story and use action plans. After diagnosis, quality of care increases when GPs and practice staff have a proactive care approach, act as interpreters of diagnosis, treatment options, and its consequences, and engage in care coordination with specialists in secondary care involving the patient.ConclusionThis scoping review identified healthcare practices that increase the quality of care in cancer trajectories from a general practice perspective. The results support general practice in investigating own healthcare practices and identifying possibilities for quality improvement.
KEY POINTS
- Identified healthcare practices in general practice that increase the quality of care in cancer trajectories:
- Listen carefully to the full story
- Use action plans and time-out-consultations
- Plan and provide proactive care
- Act as an interpreter of diagnosis, treatment options, and its consequences for the patient
- Coordinate care with specialists, patients, and caregivers with mutual respect
- Identified barriers for quality of care in cancer trajectories are:
- Time constraints in consultations
- Limited accessibility for patients and caregivers
- Health practices to increase the quality of care should be effective, safe, people-centered, timely, equitable, integrated, and efficient. These distinctions of quality of care, support general practice in investigating and improving quality of care in cancer trajectories.
90.
Martine Puts Johanne Monette Veronique Girre Nadia Sourial Christina Wolfson Michele Monette Gerald Batist Howard Bergman 《Journal of Geriatric Oncology》2013,4(4):319-326
ObjectivesTo determine the association between self-rated health (SRH) and functional status, comorbidity, toxicity of treatment and mortality in older patients with newly-diagnosed cancer.Materials and MethodsPatients aged 65 and over, newly diagnosed were recruited at the Jewish General Hospital, Montreal, Canada. SRH and functional status [instrumental activities of daily living (IADL), basic activities of daily living (ADL), Eastern Cooperative Oncology Group performance status (ECOG PS), frailty markers and number of comorbid conditions] were evaluated prior to the start of treatment, and at 3, 6 and 12 months (SRH only). Treatment toxicity and mortality data were abstracted from the chart. Logistic regression was also used to examine the relationship between functional status, comorbidity and SRH at baseline. Logistic and Cox regression were used to examine the association between baseline SRH and treatment toxicity/time to death.ResultsThere were 112 participants enrolled on this study (median age 74.1). At baseline, 74 patients (66.1%) had a good SRH and 38 patients (33.9%) had poor SRH. Only an increasing number of comorbid conditions was associated with poor SRH at baseline in both univariate and multivariable analysis. We found no association between SRH and toxicity or mortality.ConclusionA substantial proportion had poor SRH prior to and during cancer treatment. An increasing number of comorbidities was associated with poor SRH at baseline. SRH did not predict toxicity or mortality. Attention to comorbid conditions in older patients with cancer is warranted considering their impact on SRH in this population. 相似文献