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131.
Hemant Suryavanshi Raju D. Chaudhari Vishakha Patil Swapan Majumdar Sudhan Debnath Goutam Biswas 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2022,30(1):139
PurposeVortioxetine an anti-depressant FDA-drug recently reported showing better in vitro efficacy against SARS-CoV-2.MethodsIn this study, we have synthesized ten new derivatives having alkenes, alkynes, benzyl, aryl, and mixed carbamate at the N-terminal of vortioxetine. Then the binding energy and interactions with the crucial amino acid residues in the binding pocket of main protease (Mpro) of SARS-CoV-2, of reported and ten newly synthesized vortioxetine derivatives (total thirty-one) in comparison with remdesivir are analyzed and presented in this paper.ResultsBased on the docking scores predicted by ADV and AD, most vortioxetine derivatives showed better binding efficiency towards Mpro of SARS-CoV-2 in comparison with remdesivir (an EUA approved drug against SARS-CoV-2 Mpro) and vortioxetine.ConclusionThis study shows that some vortioxetine derivatives can be developed into promising drugs for COVID-19 treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-022-00441-z. 相似文献
132.
Anne Kuwabara Mark Cinque Taylor Ray Seth Lawrence Sherman 《Current reviews in musculoskeletal medicine》2022,15(2):90
Purpose of ReviewTo present a synthesis of recent literature regarding the treatment of patellofemoral arthritisRecent FindingsRisk factors of PFJ OA include patella malalignment or maltracking, injury to supportive structures including the MPFL, dysfunction of hamstring and quadriceps coordination, lower limb alignment, trochlear dysplasia, patellar trauma, or ACL surgery. Special physical exam maneuvers include patellar grind test, apprehension test, and lateral patellar tilt angle. Radiographs that should be obtained first-line include weight bearing bilateral AP, lateral, and Merchant views. CT and MRI are used to assess trochlear dysplasia, excessive patellar height, and TT-TG distance. Non-operative management options discussed include non-pharmacologic treatment (patient education, self-management, physical therapy, weight loss), ESWT, cold therapy, taping, bracing, and orthotics. Pharmacologic management options discussed include NSAIDs, acetaminophen, oral narcotics, and duloxetine. Injection therapies include glucocorticoids, hyaluronic acid, PRP, and other regenerative therapies (BMAC, adipose, or mesenchymal stem cells). Other treatment options include radiofrequency ablation and botulinum toxin. The algorithm for the surgical treatment of PFJ OA can begin with arthroscopic assessment of the PF articular cartilage to address mechanical symptoms and to evaluate/treat lateral soft tissue with or without overhanging lateral osteophytes. If patients fail to have symptomatic improvement, a TTO can be considered in those patients less than 50 years of age or active patients >50 years old. In patients with severe PFJ OA, refractory to the above treatments, PFA should be considered. While early PFA design and technique were less than encouraging, more recent implant design and surgical technique have demonstrated robust results in the literature.SummaryPatellofemoral osteoarthritis is a challenging orthopedic problem to treat, in that it can often affect younger patients, with otherwise well-functioning knees. It is a unique entity compared to TF OA with distinct epidemiology, biomechanics and risk factors and treatment options. 相似文献
133.
Rosengren DB Beadnell B Nason M Stafford PA Daugherty R 《Substance abuse treatment, prevention, and policy》2012,7(1):19-14
ABSTRACT: BACKGROUND: There is significant interest in the value of motivational approaches that enhance participant readiness to change, but less is known about clients' self-reports of problematic behavior when participating in such interventions. METHODS: We examined whether participants in a motivationally-based intervention for DUI offenders changed their reports of substance use at postintervention (when reporting on the same 30 days that they reported on at preintervention). Specifically, Study 1 (N = 8,387) tested whether participants in PRIME For Life (PFL) changed their reports about baseline substance levels when asked at postintervention versus at preintervention. Study 2 (N = 192) compared changes in self-reported baseline drinking between PFL and intervention as usual (IAU) participants. RESULTS: Many participants in Study 1 did not change their reports about how much they used substances during the 30-day period before baseline. Among those who did, the most common change was an increase in reported amounts of baseline drug use, and typical and peak alcohol use. This sample also showed changes in reports of their baseline pattern of high-risk-use (consistent versus occasional). At postintervention, participants who were younger, single, or endorsing more indicators of alcohol dependence were more likely to later report greater frequency of baseline drug use, and greater peak and typical number of baseline drinks. Gender, education, and race were also associated with reporting inconsistency on some behaviors. In Study 2, PFL participants showed greater increases in reports of peak alcohol use compared to IAU, but both conditions showed similar increases for drugs and typical alcohol use. CONCLUSIONS: In both research and clinical settings, a segment of participants may initially report less substance use than they do when asked later about the same baseline period. These preliminary findings suggest clinicians and researchers may find postintervention evaluations yield reports of greater baseline alcohol or drug use for some people. For some behaviors, this may occur more often in interventions that target client motivation. Future research should attempt to identify which reports - preintervention vs. postintervention - better reflect actual baseline substance use. 相似文献
134.
Raymond Wong David Ray David A. Kendall 《The Journal of pharmacy and pharmacology》2012,64(11):1614-1620
Objectives Progesterone has been shown to be neuroprotective in a number of preclinical central nervous system injury models including cerebral ischaemia. The aim of this study was to clarify differences in outcomes owing to different dosing regimens and the pharmacokinetic profile of progesterone, particularly in relation to brain levels. Methods Male C57 Bl/6 mice were injected intraperitoneally with progesterone (8 mg/kg in dimethylsulfoxide) or with a bolus injection followed by continuous subcutaneous infusion (1.0 µl/h of a 50 mg/ml progesterone solution) via implanted osmotic minipumps. Plasma and brain samples were collected over 24 h from bolus‐injected mice and 48 h from mice implanted with minipumps. Progesterone concentrations were measured by an enzyme‐linked immunoassay and pharmacokinetic profiles were constructed. Key findings Intraperitoneally injected progesterone had a short half‐life (fast component half‐life of 0.2 h) in both plasma and brain. Minipump delivery resulted in higher concentrations of progesterone in plasma and particularly in brain over a longer period. The volume of distribution with intraperitoneal injection was 172.78 versus 1641.84 ng/h per g via minipump in the first 24 h. Conclusions A bolus intraperitoneal loading dose of progesterone followed by continuous delivery via osmotic minipump is an effective way of delivering progesterone to the brain. 相似文献
135.
136.
Charles E. Ray Catherine Battaglia Anne M. Libby Allan Prochazka Stan Xu Brian Funaki 《Journal of vascular and interventional radiology : JVIR》2012,23(3):306-314
PurposeTo determine whether there is a cost advantage for one of the three commonly performed interventional radiology (IR) procedures (chemoembolization, selective internal radiation therapy [SIRT], radiofrequency ablation [RFA]) in the treatment of hepatocellular carcinoma (HCC).Materials and MethodsA cost analysis from the payer perspective was performed. Primary data were collected from a university hospital, and sensitivity testing was done by comparing coding information obtained at two other tertiary care medical facilities. Medicare allowable reimbursements were used to estimate costs. Decision analytic models using decision tree analysis and Monte Carlo simulations were used to compare alternatives. Simulations were performed comparing all three procedures, followed by a two-way comparison of chemoembolization and SIRT.ResultsSimple decision tree analyses showed that RFA was less expensive compared with chemoembolization and SIRT. Monte Carlo simulations showed average reimbursements for each of the three procedures that was largely dependent on the number of repeat procedures required ($9,362 vs $30,107 vs $35,629 for RFA, chemoembolization, and SIRT; P < .001). When comparing only chemoembolization and SIRT, chemoembolization was the lower cost strategy in most scenarios, but SIRT was lower in cost in more than one-third of the simulations.ConclusionsRFA was the least costly of the three IR strategies in nearly all scenarios studied in these models. Although chemoembolization was less expensive than SIRT in most instances, Monte Carlo simulation showed a preference for SIRT in more than one-third of all scenarios. Sensitivity analyses showed that the most important variables assessed were the need for repeat procedures. 相似文献
137.
Anindita Dutta Sanghita Roychoudhury Saswati Chowdhury Manas Ranjan Ray 《International journal of hygiene and environmental health》2013,216(3):301-308
To perform sputum analysis for verification of pulmonary changes in premenopausal rural Indian women chronically exposed to biomass smoke during cooking.Three consecutive morning sputum samples were collected from 196 women (median age 34 years) cooking with biomass and 149 age-matched control women cooking with cleaner fuel liquefied petroleum gas. Smears made on slides were stained with Papanicolaou and Perl's Prussian blue. Airway oxidative stress was estimated as reactive oxygen species (ROS) generation (by flow cytometry) and superoxide dismutase (SOD) level (by spectrophotometry) in sputum cells. Airway inflammation was measured as sputum levels of interleukin (IL)-6, -8 and tumor necrosis factor- alpha (TNF-α). Particulate matter of diameter less than 10 (PM10) was measured using laser photometer while benzene exposure was monitored by measuring trans, trans-muconic acid (t,t-MA) in urine by HPLC-UV. Compared with control, sputum of biomass users contained more neutrophils, lymphocytes, eosinophils, alveolar macrophages, and showed presence of ciliocytophthoria, Charcot-Leyden crystals, Curschmann's spiral. ROS generation was increased by 2-fold while SOD was depleted by 31% in biomass users. They also had higher sputum levels of IL-6, -8 and TNF-α. Levels of PM10 and t,t-MA were 2.9- and 5.8-times higher in biomass-using women. PM10 and t,t-MA levels were positively associated with cellular changes in the sputum, markers of airway inflammation, and oxidative stress. Cooking with biomass alters sputum cytology, and increases airway inflammation and oxidative stress that might result in further amplification of the tissue damaging cascade in women chronically exposed to biomass smoke. 相似文献
138.
Anna Ehrlich Paramita Ray Kathryn E. Luker Elias J. Lolis Gary D. Luker 《Biochemical pharmacology》2013
The chemokine CXCL12 and its shared seven-transmembrane receptors CXCR4 and CXCR7 regulate diseases including cancer, atherosclerosis, autoimmunity, and HIV infection, making these molecules promising drug targets. These molecules also control key processes in normal development and physiology, suggesting the need to selectively modulate CXCR4 and/or CXCR7 functions and signaling to reduce potential complications of long-term therapy. We previously identified two peptides that functioned as allosteric agonists driving CXCR4-dependent chemotaxis, providing key structural information to design a small number of additional peptides to investigate determinants of CXCL12 interactions and signaling through CXCR4 and CXCR7. In the current study, we show that the previously identified peptides only minimally activated CXCR4 signaling through the cytosolic adapter protein β-arrestin 2 and do not initiate signaling to ERK1/2. By comparison, peptides with diverse N-terminal amino acid sequences effectively activated CXCR7 signaling to β-arrestin 2. One peptide, designated as GSLW based on its N-terminal amino acids, activated CXCR7 signaling and potentiated CXCL12-CXCR7 signaling without blocking the scavenger function of CXCR7 to internalize CXCL12. These results advance our understanding of CXCR7 ligand recognition and signaling, and provide structural information to target allosteric binding sites on this receptor as chemical probes and potential therapeutic agents. 相似文献
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140.