Drug Target Insights最新文献_第3页

First-line tepotinib for a very elderly patient with metastatic NSCLC harboring MET exon 14 skipping mutation and high PD-L1 expression. 一线替波替尼用于一名患有转移性NSCLC的高龄患者，该患者携带MET外显子14跳跃突变和高PD-L1表达。

IF 2.7

Drug Target Insights Pub Date : 2023-10-06 eCollection Date: 2023-01-01 DOI: 10.33393/dti.2023.2626

Alessandro Inno, Giuseppe Bogina, Giulio Settanni, Matteo Salgarello, Giovanni Foti, Carlo Pomari, Vincenzo Picece, Stefania Gori

{"title":"First-line tepotinib for a very elderly patient with metastatic NSCLC harboring MET exon 14 skipping mutation and high PD-L1 expression.","authors":"Alessandro Inno, Giuseppe Bogina, Giulio Settanni, Matteo Salgarello, Giovanni Foti, Carlo Pomari, Vincenzo Picece, Stefania Gori","doi":"10.33393/dti.2023.2626","DOIUrl":"10.33393/dti.2023.2626","url":null,"abstract":"Optimal treatment for metastatic non-small cell lung cancer (NSCLC) with mesenchymal epithelial transition gene (MET) exon 14 skipping mutation has not been established yet. MET inhibitors were demonstrated to be effective and tolerated in patients with this condition, while evidence on safety and efficacy of immunotherapy and/or chemotherapy in this population is limited. Here we report the case of an 86-year-old male with metastatic NSCLC harboring MET exon 14 skipping mutation and with high programmed cell death ligand 1 (PD-L1) expression (tumor proportion score ≥50%). The patient received the MET inhibitor tepotinib as first-line treatment, achieving a partial response, with G2 peripheral edema as adverse event that was successfully managed with temporary discontinuation, dose reduction, diuretics and physical therapy. After 31 months, the patient is still receiving tepotinib, with an ongoing response. Tepotinib is a valuable therapeutic option for first-line treatment of older patients with NSCLC harboring MET exon 14 skipping mutation, even in the presence of high PD-L1 expression.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"17 ","pages":"110-113"},"PeriodicalIF":2.7,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fc/1e/dti-17-110.PMC10568218.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of anti-pathogenic activity among in silico predicted small-molecule inhibitors of Pseudomonas aeruginosa LasR or nitric oxide reductase (NOR). 在硅预测的铜绿假单胞菌LasR或一氧化氮还原酶（NOR）小分子抑制剂中鉴定抗致病活性。

IF 2.7

Drug Target Insights Pub Date : 2023-09-28 eCollection Date: 2023-01-01 DOI: 10.33393/dti.2023.2638

Gemini Gajera, Niel Henriksen, Bryan Cox, Vijay Kothari

{"title":"Identification of anti-pathogenic activity among in silico predicted small-molecule inhibitors of Pseudomonas aeruginosa LasR or nitric oxide reductase (NOR).","authors":"Gemini Gajera, Niel Henriksen, Bryan Cox, Vijay Kothari","doi":"10.33393/dti.2023.2638","DOIUrl":"10.33393/dti.2023.2638","url":null,"abstract":"Introduction: Antibiotic-resistant Pseudomonas aeruginosa strains cause considerable morbidity and mortality globally. Identification of novel targets in this notorious pathogen is urgently warranted to facilitate discovery of new anti-pathogenic agents against it. This study attempted to identify small-molecule inhibitors of two important proteins LasR and nitric oxide reductase (NOR) in P. aeruginosa. 'Las' system can be said to be the 'master' regulator of quorum sensing in P. aeruginosa, whose receptor protein is LasR. Similarly, NOR is crucial to detoxification of reactive nitrogen species.Methods: In silico identification of potential LasR or NOR inhibitors was attempted through a virtual screening platform AtomNet® to obtain a final subset of <100 top scoring compounds. These compounds were evaluated for their in vivo anti-pathogenic activity by challenging the model host Caenorhabditis elegans with P. aeruginosa in the presence or absence of test compounds. Survival of the worm population in 24-well assay plates was monitored over a period of 5 days microscopically.Results: Of the 96 predicted LasR inhibitors, 11 exhibited anti-Pseudomonas activity (23%-96% inhibition of bacterial virulence as per third-day end-point) at 25-50 µg/mL. Of the 85 predicted NOR inhibitors, 8 exhibited anti-Pseudomonas activity (40%-85% inhibition of bacterial virulence as per second-day end-point) at 25-50 µg/mL.Conclusion: Further investigation on molecular mode of action of compounds found active in this study is warranted. Virtual screening can be said to be a useful tool in narrowing down the list of compounds requiring actual wet-lab screening, saving considerable time and efforts for drug discovery.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"17 ","pages":"101-109"},"PeriodicalIF":2.7,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bf/04/dti-17-101.PMC10551673.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41108367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ESBL and carbapenemase-producing Enterobacteriaceae in infectious pleural effusions: current epidemiology at Hôpital du Mali. 感染性胸腔积液中ESBL和产碳青霉烯酶的肠杆菌科：马里医院的当前流行病学。

IF 2.7

Drug Target Insights Pub Date : 2023-08-29 eCollection Date: 2023-01-01 DOI: 10.33393/dti.2023.2613

Aimé Césaire Kalambry, Tchamou Malraux Fleury Potindji, Ibrehima Guindo, Ambara Kassogue, Boubacar Sidiki Ibrahim Drame, Seydou Togo, Sadio Yena, Seydou Doumbia, Mahamadou Diakite

{"title":"ESBL and carbapenemase-producing Enterobacteriaceae in infectious pleural effusions: current epidemiology at Hôpital du Mali.","authors":"Aimé Césaire Kalambry, Tchamou Malraux Fleury Potindji, Ibrehima Guindo, Ambara Kassogue, Boubacar Sidiki Ibrahim Drame, Seydou Togo, Sadio Yena, Seydou Doumbia, Mahamadou Diakite","doi":"10.33393/dti.2023.2613","DOIUrl":"10.33393/dti.2023.2613","url":null,"abstract":"Background: Antimicrobial resistance (AMR) is a global health concern, with extended-spectrum β-lactamases (ESBLs) and carbapenemases being major contributors. Pleural infection (PI) is a severe condition in West Africa, complicated by AMR. This study aimed to investigate the prevalence and molecular characteristics of ESBL and carbapenemase-producing enterobacteria in pleural effusions in Mali.Materials and methods: Pleural fluid samples from 526 patients with pleuritis were analyzed. Enterobacterial species were isolated and identified, and the prevalence of resistance genes (blaOXA-48, blaNDM-1, blaKPC, blaTEM, blaSHV) and virulence factors was determined.Results: Among the patients, 110 were diagnosed with enterobacterial pleuritis. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were the main pathogens identified. Resistance to β-lactams and cephalosporins was high, while carbapenems showed good activity. ESBL production was detected in 33.6% of isolates, with blaTEM being the most common gene. Carbapenemase gene (blaNDM-1) was found in three isolates.Conclusion: The study highlights the high prevalence of multidrug-resistant bacteria and the need for appropriate antibiotic selection based on local resistance patterns. Understanding the molecular characteristics of resistance is crucial for optimizing patient care and developing effective therapeutic strategies. Further research is needed to monitor and control AMR in PIs in Mali.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"17 ","pages":"92-100"},"PeriodicalIF":2.7,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e1/3b/dti-17-92.PMC10466504.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of anti-pathogenic activity among in silico predicted small-molecule inhibitors of Pseudomonas aeruginosa LasR or nitric oxide reductase (NOR) 铜绿假单胞菌LasR或一氧化氮还原酶(NOR)的计算机预测小分子抑制剂的抗病原活性鉴定

IF 2.7

Drug Target Insights Pub Date : 2023-07-17 DOI: 10.1101/2023.07.17.549273

G. Gajera, N. Henriksen, Bryan Cox, V. Kothari

{"title":"Identification of anti-pathogenic activity among in silico predicted small-molecule inhibitors of Pseudomonas aeruginosa LasR or nitric oxide reductase (NOR)","authors":"G. Gajera, N. Henriksen, Bryan Cox, V. Kothari","doi":"10.1101/2023.07.17.549273","DOIUrl":"https://doi.org/10.1101/2023.07.17.549273","url":null,"abstract":"Antibiotic resistant Pseudomonas aeruginosa strains cause considerable morbidity and mortality. Identification of novel targets in this notorious pathogen is urgently warranted to facilitate discovery of new anti-pathogenic agents acting against it. Attacking non-essential targets is believed to be a potential anti-virulence strategy. This study attempted to identify small molecule inhibitors of two important proteins LasR and nitric oxide reductase (NOR) in P. aeruginosa. This bacterial pathogen possesses multiple quorum sensing (QS) systems to regulate expression of many of its genes including those associated with virulence. Among these QS systems, ‘Las’ system can be said to be the ‘master’ regulator, whose receptor protein is LasR. Similarly, NOR plays crucial role in detoxification of reactive nitrogen species. This study attempted in silico identification of potential LasR or NOR inhibitors through a virtual screen employing AtomNet®, a proprietary deep learning neural network. Following virtual screening of a large number of compounds for their affinity to LasR or NOR, a final subset of <100 compounds was created by clustering and filtering the top scoring compounds. These compounds were evaluated for their in vivo anti-pathogenic activity by challenging the model host Caenorhabditis elegans with P. aeruginosa in presence or absence of test compounds. Survival of the worm population in 24-well assay plates was monitored over a period of 5 days microscopically. Of the 96 predicted LasR inhibitors, 11 exhibited anti-Pseudomonas activity (23-96% inhibition of bacterial virulence as per third-day end point) at 25-50 µg/ml. Of the 85 predicted NOR inhibitors, 8 exhibited anti-Pseudomonas activity (40-85% inhibition of bacterial virulence as per second-day end point) at 25-50 µg/ml. Further investigation on molecular mode of action of active compounds is warranted.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"17 1","pages":"101 - 109"},"PeriodicalIF":2.7,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45888013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Licorice as a herbal extract in periodontal therapy. 甘草作为一种草药提取物用于牙周治疗。

IF 2.7

Drug Target Insights Pub Date : 2023-06-05 eCollection Date: 2023-01-01 DOI: 10.33393/dti.2023.2583

Safiya Fatima Khan, Bhavya Shetty, Ibrahim Fazal, Asim Mustafa Khan, Faheem Muzaffar Mir, Muhamood Moothedath, V J Reshma, Muhaseena Muhamood

{"title":"Licorice as a herbal extract in periodontal therapy.","authors":"Safiya Fatima Khan, Bhavya Shetty, Ibrahim Fazal, Asim Mustafa Khan, Faheem Muzaffar Mir, Muhamood Moothedath, V J Reshma, Muhaseena Muhamood","doi":"10.33393/dti.2023.2583","DOIUrl":"10.33393/dti.2023.2583","url":null,"abstract":"Periodontal disease is caused by specific pathogens which results in inflammation of the tooth-supporting structures and subsequently causes the continued breakdown of alveolar bone and periodontal ligament. Licorice (Glycyrrhiza glabra) is a perennial herb with substantial medicinal value. Licorice extract is derived from dried, unpeeled stolons and roots of Glycyrrhiza uralensis and G. glabra. The bioactive ingredients in licorice extract such as glycyrrhizin, licoricidin, glabridin, licochalcone A, and licorisoflavan A have anti-inflammatory, antimicrobial, and anti-adherence effects that are beneficial against periodontal disease. Since periodontal disease has a complex etiology that includes the host response and microorganisms, licorice phytochemicals offer a therapeutic advantage due to their dual functionality. The aim of this review was to enumerate the bioactive compounds present in herbal licorice extract and to elucidate the beneficial effects of licorice and its derivatives in periodontal therapy. Literature review and clinical trials evaluating the effect of licorice on periodontopathogens and periodontal disease are included in this article.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"17 ","pages":"70-77"},"PeriodicalIF":2.7,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/86/dti-17-70.PMC10243202.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9597793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Licorice as a herbal extract in periodontal therapy 甘草提取物在牙周治疗中的应用

Drug Target Insights Pub Date : 2023-06-05 DOI: 10.33393/dti.2023.2583

Safiya Fatima Khan, Bhavya Shetty, Ibrahim Fazal, Asim Mustafa Khan, Faheem Muzaffar Mir, Muhamood Moothedath, Reshma VJ, Muhaseena Muhamood

{"title":"Licorice as a herbal extract in periodontal therapy","authors":"Safiya Fatima Khan, Bhavya Shetty, Ibrahim Fazal, Asim Mustafa Khan, Faheem Muzaffar Mir, Muhamood Moothedath, Reshma VJ, Muhaseena Muhamood","doi":"10.33393/dti.2023.2583","DOIUrl":"https://doi.org/10.33393/dti.2023.2583","url":null,"abstract":"Periodontal disease is caused by specific pathogens which results in inflammation of the tooth-supporting structures and subsequently causes the continued breakdown of alveolar bone and periodontal ligament. Licorice (Glycyrrhiza glabra) is a perennial herb with substantial medicinal value. Licorice extract is derived from dried, unpeeled stolons and roots of Glycyrrhiza uralensis and G. glabra. The bioactive ingredients in licorice extract such as glycyrrhizin, licoricidin, glabridin, licochalcone A, and licorisoflavan A have anti-inflammatory, antimicrobial, and anti-adherence effects that are beneficial against periodontal disease. Since periodontal disease has a complex etiology that includes the host response and microorganisms, licorice phytochemicals offer a therapeutic advantage due to their dual functionality. The aim of this review was to enumerate the bioactive compounds present in herbal licorice extract and to elucidate the beneficial effects of licorice and its derivatives in periodontal therapy. Literature review and clinical trials evaluating the effect of licorice on periodontopathogens and periodontal disease are included in this article.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135658074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Network analysis for identifying potential anti-virulence targets from whole transcriptome of Pseudomonas aeruginosa and Staphylococcus aureus exposed to certain anti-pathogenic polyherbal formulations. 从暴露于某些抗病原多草药制剂的铜绿假单胞菌和金黄色葡萄球菌的全转录组中识别潜在抗病毒靶标的网络分析。

IF 2.7

Drug Target Insights Pub Date : 2023-05-29 eCollection Date: 2023-01-01 DOI: 10.33393/dti.2023.2595

Feny J Ruparel, Siddhi K Shah, Jhanvi H Patel, Nidhi R Thakkar, Gemini N Gajera, Vijay O Kothari

{"title":"Network analysis for identifying potential anti-virulence targets from whole transcriptome of Pseudomonas aeruginosa and Staphylococcus aureus exposed to certain anti-pathogenic polyherbal formulations.","authors":"Feny J Ruparel, Siddhi K Shah, Jhanvi H Patel, Nidhi R Thakkar, Gemini N Gajera, Vijay O Kothari","doi":"10.33393/dti.2023.2595","DOIUrl":"10.33393/dti.2023.2595","url":null,"abstract":"Introduction: Antimicrobial resistance (AMR) is a serious global threat. Identification of novel antibacterial targets is urgently warranted to help antimicrobial drug discovery programs. This study attempted identification of potential targets in two important pathogens Pseudomonas aeruginosa and Staphylococcus aureus.Methods: Transcriptomes of P. aeruginosa and S. aureus exposed to two different quorum-modulatory polyherbal formulations were subjected to network analysis to identify the most highly networked differentially expressed genes (hubs) as potential anti-virulence targets.Results: Genes associated with denitrification and sulfur metabolism emerged as the most important targets in P. aeruginosa. Increased buildup of nitrite (NO2) in P. aeruginosa culture exposed to the polyherbal formulation Panchvalkal was confirmed through in vitro assay too. Generation of nitrosative stress and inducing sulfur starvation seemed to be effective anti-pathogenic strategies against this notorious gram-negative pathogen. Important targets identified in S. aureus were the transcriptional regulator sarA, immunoglobulin-binding protein Sbi, serine protease SplA, the saeR/S response regulator system, and gamma-hemolysin components hlgB and hlgC.Conclusion: Further validation of the potential targets identified in this study is warranted through appropriate in vitro and in vivo assays in model hosts. Such validated targets can prove vital to many antibacterial drug discovery programs globally.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"17 ","pages":"58-69"},"PeriodicalIF":2.7,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/69/dti-17-58.PMC10238913.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9584080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Network analysis for identifying potential anti-virulence targets from whole transcriptome of Pseudomonas aeruginosa and Staphylococcus aureus exposed to certain anti-pathogenic polyherbal formulations 从暴露于某些抗致病性多药制剂的铜绿假单胞菌和金黄色葡萄球菌的全转录组中鉴定潜在的抗毒靶点的网络分析

Drug Target Insights Pub Date : 2023-05-29 DOI: 10.33393/dti.2023.2595

Feny J. Ruparel, Siddhi K. Shah, Jhanvi H. Patel, Nidhi R. Thakkar, Gemini N. Gajera, Vijay O. Kothari

{"title":"Network analysis for identifying potential anti-virulence targets from whole transcriptome of Pseudomonas aeruginosa and Staphylococcus aureus exposed to certain anti-pathogenic polyherbal formulations","authors":"Feny J. Ruparel, Siddhi K. Shah, Jhanvi H. Patel, Nidhi R. Thakkar, Gemini N. Gajera, Vijay O. Kothari","doi":"10.33393/dti.2023.2595","DOIUrl":"https://doi.org/10.33393/dti.2023.2595","url":null,"abstract":"Introduction: Antimicrobial resistance (AMR) is a serious global threat. Identification of novel antibacterial targets is urgently warranted to help antimicrobial drug discovery programs. This study attempted identification of potential targets in two important pathogens Pseudomonas aeruginosa and Staphylococcus aureus. Methods: Transcriptomes of P. aeruginosa and S. aureus exposed to two different quorum-modulatory polyherbal formulations were subjected to network analysis to identify the most highly networked differentially expressed genes (hubs) as potential anti-virulence targets. Results: Genes associated with denitrification and sulfur metabolism emerged as the most important targets in P. aeruginosa. Increased buildup of nitrite (NO2) in P. aeruginosa culture exposed to the polyherbal formulation Panchvalkal was confirmed through in vitro assay too. Generation of nitrosative stress and inducing sulfur starvation seemed to be effective anti-pathogenic strategies against this notorious gram-negative pathogen. Important targets identified in S. aureus were the transcriptional regulator sarA, immunoglobulin-binding protein Sbi, serine protease SplA, the saeR/S response regulator system, and gamma-hemolysin components hlgB and hlgC. Conclusion: Further validation of the potential targets identified in this study is warranted through appropriate in vitro and in vivo assays in model hosts. Such validated targets can prove vital to many antibacterial drug discovery programs globally.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135693233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Treatment with levosimendan in an experimental model of early ventilator-induced diaphragmatic dysfunction. 在早期呼吸机诱发膈肌功能障碍的实验模型中使用左西孟旦治疗。

IF 2

Drug Target Insights Pub Date : 2023-04-13 eCollection Date: 2023-01-01 DOI: 10.33393/dti.2023.2574

Vanessa Zambelli, Emma J Murphy, Paolo Delvecchio, Laura Rizzi, Roberto Fumagalli, Emanuele Rezoagli, Giacomo Bellani

{"title":"Treatment with levosimendan in an experimental model of early ventilator-induced diaphragmatic dysfunction.","authors":"Vanessa Zambelli, Emma J Murphy, Paolo Delvecchio, Laura Rizzi, Roberto Fumagalli, Emanuele Rezoagli, Giacomo Bellani","doi":"10.33393/dti.2023.2574","DOIUrl":"10.33393/dti.2023.2574","url":null,"abstract":"Introduction: Mechanical ventilation (MV) is a life-saving approach in critically ill patients. However, it may affect the diaphragmatic structure and function, beyond the lungs. Levosimendan is a calcium sensitizer widely used in clinics to improve cardiac contractility in acute heart failure patients. In vitro studies have demonstrated that levosimendan increased force-generating capacity of the diaphragm in chronic obstructive pulmonary disease patients. Thus the aim of this study was to evaluate the effects of levosimendan administration in an animal model of ventilator-induced diaphragmatic dysfunction (VIDD) on muscle contraction and diaphragm muscle cell viability.Methods: Sprague-Dawley rats underwent prolonged MV (5 hours). VIDD+Levo group received a starting bolus of levosimendan immediately after intratracheal intubation and then an intravenous infusion of levosimendan throughout the study. Diaphragms were collected for ex vivo contractility measurement (with electric stimulation), histological analysis and Western blot analysis. Healthy rats were used as the control.Results: Levosimendan treatment maintained an adequate mean arterial pressure during the entire experimental protocol, preserved levels of autophagy-related proteins (LC3BI and LC3BII) and the muscular cell diameter demonstrated by histological analysis. Levosimendan did not affect the diaphragmatic contraction or the levels of proteins involved in the protein degradation (atrogin).Conclusions: Our data suggest that levosimendan preserves muscular cell structure (cross-sectional area) and muscle autophagy after 5 hours of MV in a rat model of VIDD. However, levosimendan did not improve diaphragm contractile efficiency.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"17 ","pages":"39-44"},"PeriodicalIF":2.0,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/41/dti-17-39.PMC10105369.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9324491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A systematic review of mucoadhesive vaginal tablet testing. 粘液阴道片剂测试的系统回顾。

IF 2

Drug Target Insights Pub Date : 2023-01-16 eCollection Date: 2023-01-01 DOI: 10.33393/dti.2023.2477

Ismin Zainol Abidin, Emma J Murphy, Gustavo Waltzer Fehrenbach, Emanuele Rezoagli, Noel Gately, Ian Major

引用次数: 0