Drug Target Insights最新文献_第5页

MRSA carriage among healthcare workers in a Vietnamese intensive care unit: a prospective cohort study. 越南重症监护病房医护人员携带MRSA:一项前瞻性队列研究。

IF 2.7 Q3 PHARMACOLOGY & PHARMACY

Drug Target Insights

Pub Date : 2022-01-01 DOI: 10.33393/dti.2022.2504

Thuy B Duong, Minh C Duong, James I Campbell, Hoang V M Nguyen, Hien H Nguyen, Hanh T B Bui, Chau V V Nguyen, Anita Heywood

ABSTRACT Background: Little is known about the magnitude and patterns of methicillin-resistant Staphylococcus aureus (MRSA) carriage among intensive care unit (ICU) healthcare workers (HCWs), especially in lower-middle-income countries like Vietnam. Materials and methods: A prospective cohort study was conducted on HCWs working in the adult ICU of the Hospital for Tropical Diseases in Vietnam between October 28 and December 20, 2019. These HCWs included physicians, nurses, and nursing assistants who were responsible for all essential medical activities and basic patient care. A questionnaire was used to collect participants’ information, including age, sex, profession, ICU working time, and underlying diseases. Hand and nasal swabs were collected weekly for 8 consecutive weeks for MRSA screening. Staphylococcal isolates were checked for catalase and coagulase and, for methicillin resistance using cefoxitin disk diffusion, then rechecked on the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: Among 55 HCWs, 16 (29.1%) carried MRSA in their noses or hands. MRSA intermittent hand carriage was documented in 2 (3.6%) HCWs. Among 53 HCWs undertaking nasal swabs, 13 (24.5%) were MRSA persistent and 3 (5.6%) were intermittent carriers. The MRSA carriage rate was highest among nursing assistants (50%, 4/8). More HCWs with underlying diseases were found to be MRSA carriers (31.8%, 7/22) compared with those without comorbidities (27.3%, 9/33). Conclusion: MRSA carriage among HCWs is not rare. The findings highlight an urgent need to review and update the local infection prevention and control measures to prevent MRSA transmission from HCWs to patients.

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引用次数: 0

Antibiotic-resistant bacteria originating from the gut may modulate the mucosal immune response during sepsis and septic shock. 来自肠道的耐抗生素细菌可能在脓毒症和感染性休克期间调节粘膜免疫反应。

IF 2.7 Q3 PHARMACOLOGY & PHARMACY

Drug Target Insights

Pub Date : 2022-01-01 DOI: 10.33393/dti.2022.2520

Swinder Jeet Singh Kalra, Hari Shankar, Nasim Mansoori, Dablu Lal Gupta

Abstract The enrichment and diversity of gut microbiota play an important role in sepsis, but the role of gut microbiota composition and early-life colonization in sepsis and septic shock has not yet been characterized. The impact of gut microbiota diversity on host immunological disorders and future treatments of inflammatory diseases are not yet fully elucidated. Further, the association between the microbiota and immune development in sepsis remains unknown, and the underlying mechanisms are not well understood. The altered composition of gut microbiota during sepsis is profoundly associated with a loss of commensal bacteria and an overgrowth of potentially pathogenic bacteria, especially AMR bacteria. Disruptions of gut microbiota diversity are directly associated with susceptibility to sepsis and a higher risk of adverse outcomes. Several studies have confirmed that a mutual association between gut microbiota and the host is important for the metabolism of essential nutrients for the organism, for gut development, and for the maturation and development of a fully functional immune system. Therefore, understanding the gut microbiota diversity, composition, and function during various inflammatory conditions and sepsis may provide a comprehensive knowledge of the mechanisms behind the pathogenesis of gut-derived infection in diseases and the design of new treatment options (e.g., probiotics or fecal microbiota transplantation). Emerging evidence displays an important role of gut microbiota and their derived metabolites in modulating the host mucosal immune response and determining the susceptibility to, as well as outcomes of sepsis.

{"title":"Antibiotic-resistant bacteria originating from the gut may modulate the mucosal immune response during sepsis and septic shock.","authors":"Swinder Jeet Singh Kalra, Hari Shankar, Nasim Mansoori, Dablu Lal Gupta","doi":"10.33393/dti.2022.2520","DOIUrl":"https://doi.org/10.33393/dti.2022.2520","url":null,"abstract":"Abstract The enrichment and diversity of gut microbiota play an important role in sepsis, but the role of gut microbiota composition and early-life colonization in sepsis and septic shock has not yet been characterized. The impact of gut microbiota diversity on host immunological disorders and future treatments of inflammatory diseases are not yet fully elucidated. Further, the association between the microbiota and immune development in sepsis remains unknown, and the underlying mechanisms are not well understood. The altered composition of gut microbiota during sepsis is profoundly associated with a loss of commensal bacteria and an overgrowth of potentially pathogenic bacteria, especially AMR bacteria. Disruptions of gut microbiota diversity are directly associated with susceptibility to sepsis and a higher risk of adverse outcomes. Several studies have confirmed that a mutual association between gut microbiota and the host is important for the metabolism of essential nutrients for the organism, for gut development, and for the maturation and development of a fully functional immune system. Therefore, understanding the gut microbiota diversity, composition, and function during various inflammatory conditions and sepsis may provide a comprehensive knowledge of the mechanisms behind the pathogenesis of gut-derived infection in diseases and the design of new treatment options (e.g., probiotics or fecal microbiota transplantation). Emerging evidence displays an important role of gut microbiota and their derived metabolites in modulating the host mucosal immune response and determining the susceptibility to, as well as outcomes of sepsis.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"16 ","pages":"81-87"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/80/dti-16-81.PMC9886009.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9252330","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

Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury. 赫萨瑞林调节急性肺损伤的肺力学、炎症和纤维化。

IF 2.7 Q3 PHARMACOLOGY & PHARMACY

Drug Target Insights

Pub Date : 2021-11-27 eCollection Date: 2021-01-01 DOI: 10.33393/dti.2021.2347

Vanessa Zambelli, Laura Rizzi, Paolo Delvecchio, Elena Bresciani, Emanuele Rezoagli, Laura Molteni, Ramona Meanti, Maria Serena Cuttin, Giorgio Bovo, Silvia Coco, Robert J Omeljaniuk, Vittorio Locatelli, Giacomo Bellani, Antonio Torsello

ABSTRACT Introduction: Acute respiratory distress syndrome (ARDS) is an acute form of diffuse lung injury characterized by (i) an intense inflammatory response, (ii) increased pulmonary vascular permeability, and (iii) the loss of respiratory pulmonary tissue. In this article we explore the therapeutic potential of hexarelin, a synthetic hexapeptide growth hormone secretagogue (GHS), in an experimental model of ARDS. Hexarelin has anti-inflammatory properties and demonstrates cardiovascular-protective activities including the inhibition of cardiomyocyte apoptosis and cardiac fibrosis, both of which may involve the angiotensin-converting enzyme (ACE) system. Methods: In our experimental model, ARDS was induced by the instillation of 100 mM HCl into the right bronchus; these mice were treated with hexarelin (320 μg/kg, ip) before (Pre) or after (Post) HCl challenge, or with vehicle. Respiratory system compliance, blood gas analysis, and differential cell counts in a selective bronchoalveolar lavage (BAL) were determined 6 or 24 hours after HCl instillation. In an extended study, mice were observed for a subsequent 14 days in order to assess lung fibrosis. Results: Hexarelin induced a significant improvement in lung compliance and a reduction of the number of total immune cells in BAL 24 hours after HCl instillation, accompanied with a lower recruitment of neutrophils compared with the vehicle group. At day 14, hexarelin-treated mice presented with less pulmonary collagen deposition compared with vehicle-treated controls. Conclusions: Our data suggest that hexarelin can inhibit the early phase of the inflammatory response in a murine model of HCl-induced ARDS, thereby blunting lung remodeling processes and fibrotic development.

{"title":"Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury.","authors":"Vanessa Zambelli, Laura Rizzi, Paolo Delvecchio, Elena Bresciani, Emanuele Rezoagli, Laura Molteni, Ramona Meanti, Maria Serena Cuttin, Giorgio Bovo, Silvia Coco, Robert J Omeljaniuk, Vittorio Locatelli, Giacomo Bellani, Antonio Torsello","doi":"10.33393/dti.2021.2347","DOIUrl":"https://doi.org/10.33393/dti.2021.2347","url":null,"abstract":"ABSTRACT Introduction: Acute respiratory distress syndrome (ARDS) is an acute form of diffuse lung injury characterized by (i) an intense inflammatory response, (ii) increased pulmonary vascular permeability, and (iii) the loss of respiratory pulmonary tissue. In this article we explore the therapeutic potential of hexarelin, a synthetic hexapeptide growth hormone secretagogue (GHS), in an experimental model of ARDS. Hexarelin has anti-inflammatory properties and demonstrates cardiovascular-protective activities including the inhibition of cardiomyocyte apoptosis and cardiac fibrosis, both of which may involve the angiotensin-converting enzyme (ACE) system. Methods: In our experimental model, ARDS was induced by the instillation of 100 mM HCl into the right bronchus; these mice were treated with hexarelin (320 μg/kg, ip) before (Pre) or after (Post) HCl challenge, or with vehicle. Respiratory system compliance, blood gas analysis, and differential cell counts in a selective bronchoalveolar lavage (BAL) were determined 6 or 24 hours after HCl instillation. In an extended study, mice were observed for a subsequent 14 days in order to assess lung fibrosis. Results: Hexarelin induced a significant improvement in lung compliance and a reduction of the number of total immune cells in BAL 24 hours after HCl instillation, accompanied with a lower recruitment of neutrophils compared with the vehicle group. At day 14, hexarelin-treated mice presented with less pulmonary collagen deposition compared with vehicle-treated controls. Conclusions: Our data suggest that hexarelin can inhibit the early phase of the inflammatory response in a murine model of HCl-induced ARDS, thereby blunting lung remodeling processes and fibrotic development.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"15 ","pages":"26-33"},"PeriodicalIF":2.7,"publicationDate":"2021-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ff/34/dti-15-26.PMC8638068.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39810258","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: 4

Clinical factors predictive of appropriate treatment in COPD: a community hospital setting. 预测慢性阻塞性肺病适当治疗的临床因素：社区医院环境。

IF 2 Q3 PHARMACOLOGY & PHARMACY

Drug Target Insights

Pub Date : 2021-11-13 eCollection Date: 2021-01-01 DOI: 10.33393/dti.2021.2291

Sukanya Tongdee, Bundit Sawunyavisuth, Wattana Sukeepaisarnjaroen, Watchara Boonsawat, Sittichai Khamsai, Kittisak Sawanyawisuth

引用次数: 0

The role of patient preferences in adherence to treatment in chronic disease: a narrative review. 慢性疾病患者偏好在治疗依从性中的作用:叙述性回顾。

IF 2.7 Q3 PHARMACOLOGY & PHARMACY

Drug Target Insights

Pub Date : 2021-11-08 eCollection Date: 2021-01-01 DOI: 10.33393/dti.2021.2342

Serena Losi, Cesare Celeste Federico Berra, Riccardo Fornengo, Dario Pitocco, Giovanni Biricolti, Marco Orsini Federici

ABSTRACT Adherence to prescribed medication is important to the management of all diseases, especially those of chronic nature. Drug effectiveness is substantially compromised by therapy nonadherence. We reviewed the available evidences on the impact of patient preferences for therapy on adherence to a prescribed treatment in chronic diseases requiring long-term treatment. A search on PubMed retrieved 699 publications, leading to a selection of 12 publications: 6 on osteoporosis, 2 on moderate-to-severe asthma, 1 on type 1 diabetes, 1 on type 2 diabetes, 1 on kidney transplantation, and 1 on atrial fibrillation. Overall, 8 studies found a positive association between patient preference and adherence to therapy, while the others found no association. In general, overall adherence was considered to be high in the published studies. The reasons for a positive association included reduced dosing frequency, route of administration, lower costs, and favorable safety profile, which is related to the diverse nature of the pathology and its type and duration of treatment. A literature review suggests that achieving good adherence and persistence to therapy requires evaluation of patient preferences. In a period of increasingly limited resources, more effort is warranted to promote better adherence to therapy, especially when patients must self-manage their disease in the long term. Our results further highlight that insufficient attention has been given to the relationship between patient preference and adherence and point out the complex nature of adherence and the need for adequate patient education. More efforts are also needed to better understand the entity of cost savings for payers for specific treatments and the link with patient preference.

{"title":"The role of patient preferences in adherence to treatment in chronic disease: a narrative review.","authors":"Serena Losi, Cesare Celeste Federico Berra, Riccardo Fornengo, Dario Pitocco, Giovanni Biricolti, Marco Orsini Federici","doi":"10.33393/dti.2021.2342","DOIUrl":"https://doi.org/10.33393/dti.2021.2342","url":null,"abstract":"ABSTRACT Adherence to prescribed medication is important to the management of all diseases, especially those of chronic nature. Drug effectiveness is substantially compromised by therapy nonadherence. We reviewed the available evidences on the impact of patient preferences for therapy on adherence to a prescribed treatment in chronic diseases requiring long-term treatment. A search on PubMed retrieved 699 publications, leading to a selection of 12 publications: 6 on osteoporosis, 2 on moderate-to-severe asthma, 1 on type 1 diabetes, 1 on type 2 diabetes, 1 on kidney transplantation, and 1 on atrial fibrillation. Overall, 8 studies found a positive association between patient preference and adherence to therapy, while the others found no association. In general, overall adherence was considered to be high in the published studies. The reasons for a positive association included reduced dosing frequency, route of administration, lower costs, and favorable safety profile, which is related to the diverse nature of the pathology and its type and duration of treatment. A literature review suggests that achieving good adherence and persistence to therapy requires evaluation of patient preferences. In a period of increasingly limited resources, more effort is warranted to promote better adherence to therapy, especially when patients must self-manage their disease in the long term. Our results further highlight that insufficient attention has been given to the relationship between patient preference and adherence and point out the complex nature of adherence and the need for adequate patient education. More efforts are also needed to better understand the entity of cost savings for payers for specific treatments and the link with patient preference.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"15 ","pages":"13-20"},"PeriodicalIF":2.7,"publicationDate":"2021-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/37/ba/dti-15-13.PMC8591552.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39630611","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: 11

Tamarind (Tamarindus indica L.) Seed a Candidate Protein Source with Potential for Combating SARS-CoV-2 Infection in Obesity. 罗望子(Tamarindus indica l)培育一种有潜力对抗肥胖患者SARS-CoV-2感染的候选蛋白质来源

IF 2.7 Q3 PHARMACOLOGY & PHARMACY

Drug Target Insights

Pub Date : 2021-04-02 eCollection Date: 2021-01-01 DOI: 10.33393/dti.2021.2192

Ana H de A Morais, Amanda F de Medeiros, Isaiane Medeiros, Vanessa C O de Lima, Anna B S Luz, Bruna L L Maciel, Thaís S Passos

ABSTRACT Introduction: Obesity and coronavirus disease (COVID)-19 are overlapping pandemics, and one might worsen the other. Methods: This narrative review discusses one of the primary mechanisms to initiate acute respiratory distress syndrome, uncontrolled systemic inflammation in COVID-19, and presents a potential candidate for adjuvant treatment. Blocking the S protein binding to angiotensin-converting enzyme 2 (ACE-2) and the 3C-like protease (3CL pro) is an effective strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Results: Host proteases such as FURIN, trypsin, and transmembrane serine protease 2 (TMPRSS) act in S protein activation. Tamarind trypsin inhibitor (TTI) shows several beneficial effects on the reduction of inflammatory markers (tumor necrosis factor α [TNF-α], leptin) and biochemical parameters (fasting glycemia, triglycerides, and very low-density lipoprotein [VLDL]), in addition to improving pancreatic function and mucosal integrity in an obesity model. TTI may inhibit the action of proteases that collaborate with SARS-CoV-2 infection and the neutrophil activity characteristic of lung injury promoted by the virus. Conclusion: Thus, TTI may contribute to combating two severe overlapping problems with high cost and social complex implications, obesity and COVID-19.

{"title":"Tamarind (Tamarindus indica L.) Seed a Candidate Protein Source with Potential for Combating SARS-CoV-2 Infection in Obesity.","authors":"Ana H de A Morais, Amanda F de Medeiros, Isaiane Medeiros, Vanessa C O de Lima, Anna B S Luz, Bruna L L Maciel, Thaís S Passos","doi":"10.33393/dti.2021.2192","DOIUrl":"https://doi.org/10.33393/dti.2021.2192","url":null,"abstract":"ABSTRACT Introduction: Obesity and coronavirus disease (COVID)-19 are overlapping pandemics, and one might worsen the other. Methods: This narrative review discusses one of the primary mechanisms to initiate acute respiratory distress syndrome, uncontrolled systemic inflammation in COVID-19, and presents a potential candidate for adjuvant treatment. Blocking the S protein binding to angiotensin-converting enzyme 2 (ACE-2) and the 3C-like protease (3CL pro) is an effective strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Results: Host proteases such as FURIN, trypsin, and transmembrane serine protease 2 (TMPRSS) act in S protein activation. Tamarind trypsin inhibitor (TTI) shows several beneficial effects on the reduction of inflammatory markers (tumor necrosis factor α [TNF-α], leptin) and biochemical parameters (fasting glycemia, triglycerides, and very low-density lipoprotein [VLDL]), in addition to improving pancreatic function and mucosal integrity in an obesity model. TTI may inhibit the action of proteases that collaborate with SARS-CoV-2 infection and the neutrophil activity characteristic of lung injury promoted by the virus. Conclusion: Thus, TTI may contribute to combating two severe overlapping problems with high cost and social complex implications, obesity and COVID-19.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"15 ","pages":"5-12"},"PeriodicalIF":2.7,"publicationDate":"2021-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/4e/dti-15-05.PMC8025844.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25596557","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: 6

Corticosteroid treatment reduces headache in eosinophilic meningitis: a systematic review. 皮质类固醇治疗可减少嗜酸性脑膜炎患者的头痛:一项系统综述。

IF 2.7 Q3 PHARMACOLOGY & PHARMACY

Drug Target Insights

Pub Date : 2021-03-08 eCollection Date: 2021-01-01 DOI: 10.33393/dti.2021.2197

Sittichai Khamsai, Kittisak Sawanyawisuth, Vichai Senthong, Panita Limpawattana, Jarin Chindaprasirt, Pewpan M Intapan, Wanchai Maleewong, Somsak Tiamkao, Verajit Chotmongkol, Chetta Ngamjarus

ABSTRACT Background: Eosinophilic meningitis (EOM) is an emerging parasitic disease that can be found worldwide, of which acute severe headache is a presenting symptom. Although such headaches may persist for up to 2 months, studies have found corticosteroid to be effective in reducing this symptom. As the most recent systematic review was published in 2015, the aim of this study was to provide a more up-to-date examination of the role of corticosteroids in EOM. Methods: We included randomized controlled trials of corticosteroid treatment for EOM regardless of comparators. Research articles published in five databases were searched and evaluated. The primary outcome was headache, which was compared among various treatment regimens. Results: We found a total of 257 articles after duplication removal. Of those, two met the study criteria. According to these studies, oral prednisolone alone or in a combination of albendazole resulted in fewer patients with headache after a 2-week course of treatment compared with placebo (maximum of 9.1% vs. 45.5%). The duration of headache was also shorter in the prednisolone arm vs. placebo (maximum of 5 vs. 13 days). There were no serious side effects reported. Conclusion: A 2-week course of treatment with oral corticosteroid with or without albendazole reduced headaches in patients with EOM.

{"title":"Corticosteroid treatment reduces headache in eosinophilic meningitis: a systematic review.","authors":"Sittichai Khamsai, Kittisak Sawanyawisuth, Vichai Senthong, Panita Limpawattana, Jarin Chindaprasirt, Pewpan M Intapan, Wanchai Maleewong, Somsak Tiamkao, Verajit Chotmongkol, Chetta Ngamjarus","doi":"10.33393/dti.2021.2197","DOIUrl":"https://doi.org/10.33393/dti.2021.2197","url":null,"abstract":"ABSTRACT Background: Eosinophilic meningitis (EOM) is an emerging parasitic disease that can be found worldwide, of which acute severe headache is a presenting symptom. Although such headaches may persist for up to 2 months, studies have found corticosteroid to be effective in reducing this symptom. As the most recent systematic review was published in 2015, the aim of this study was to provide a more up-to-date examination of the role of corticosteroids in EOM. Methods: We included randomized controlled trials of corticosteroid treatment for EOM regardless of comparators. Research articles published in five databases were searched and evaluated. The primary outcome was headache, which was compared among various treatment regimens. Results: We found a total of 257 articles after duplication removal. Of those, two met the study criteria. According to these studies, oral prednisolone alone or in a combination of albendazole resulted in fewer patients with headache after a 2-week course of treatment compared with placebo (maximum of 9.1% vs. 45.5%). The duration of headache was also shorter in the prednisolone arm vs. placebo (maximum of 5 vs. 13 days). There were no serious side effects reported. Conclusion: A 2-week course of treatment with oral corticosteroid with or without albendazole reduced headaches in patients with EOM.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"15 ","pages":"1-4"},"PeriodicalIF":2.7,"publicationDate":"2021-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/fe/dti-15-01.PMC8025843.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25596554","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: 3

Interaction of drugs with lipid raft membrane domains as a possible target. 药物与脂筏膜结构域的相互作用作为可能的靶点。

IF 2.7 Q3 PHARMACOLOGY & PHARMACY

Drug Target Insights

Pub Date : 2020-12-22 eCollection Date: 2020-01-01 DOI: 10.33393/dti.2020.2185

Hironori Tsuchiya, Maki Mizogami

ABSTRACT Introduction Plasma membranes are not the homogeneous bilayers of uniformly distributed lipids but the lipid complex with laterally separated lipid raft membrane domains, which provide receptor, ion channel and enzyme proteins with a platform. The aim of this article is to review the mechanistic interaction of drugs with membrane lipid rafts and address the question whether drugs induce physicochemical changes in raft-constituting and raft-surrounding membranes. Methods Literature searches of PubMed/MEDLINE and Google Scholar databases from 2000 to 2020 were conducted to include articles published in English in internationally recognized journals. Collected articles were independently reviewed by title, abstract and text for relevance. Results The literature search indicated that pharmacologically diverse drugs interact with raft model membranes and cellular membrane lipid rafts. They could physicochemically modify functional protein-localizing membrane lipid rafts and the membranes surrounding such domains, affecting the raft organizational integrity with the resultant exhibition of pharmacological activity. Raft-acting drugs were characterized as ones to decrease membrane fluidity, induce liquid-ordered phase or order plasma membranes, leading to lipid raft formation; and ones to increase membrane fluidity, induce liquid-disordered phase or reduce phase transition temperature, leading to lipid raft disruption. Conclusion Targeting lipid raft membrane domains would open a new way for drug design and development. Since angiotensin-converting enzyme 2 receptors which are a cell-specific target of and responsible for the cellular entry of novel coronavirus are localized in lipid rafts, agents that specifically disrupt the relevant rafts may be a drug against coronavirus disease 2019.

{"title":"Interaction of drugs with lipid raft membrane domains as a possible target.","authors":"Hironori Tsuchiya, Maki Mizogami","doi":"10.33393/dti.2020.2185","DOIUrl":"https://doi.org/10.33393/dti.2020.2185","url":null,"abstract":"ABSTRACT Introduction Plasma membranes are not the homogeneous bilayers of uniformly distributed lipids but the lipid complex with laterally separated lipid raft membrane domains, which provide receptor, ion channel and enzyme proteins with a platform. The aim of this article is to review the mechanistic interaction of drugs with membrane lipid rafts and address the question whether drugs induce physicochemical changes in raft-constituting and raft-surrounding membranes. Methods Literature searches of PubMed/MEDLINE and Google Scholar databases from 2000 to 2020 were conducted to include articles published in English in internationally recognized journals. Collected articles were independently reviewed by title, abstract and text for relevance. Results The literature search indicated that pharmacologically diverse drugs interact with raft model membranes and cellular membrane lipid rafts. They could physicochemically modify functional protein-localizing membrane lipid rafts and the membranes surrounding such domains, affecting the raft organizational integrity with the resultant exhibition of pharmacological activity. Raft-acting drugs were characterized as ones to decrease membrane fluidity, induce liquid-ordered phase or order plasma membranes, leading to lipid raft formation; and ones to increase membrane fluidity, induce liquid-disordered phase or reduce phase transition temperature, leading to lipid raft disruption. Conclusion Targeting lipid raft membrane domains would open a new way for drug design and development. Since angiotensin-converting enzyme 2 receptors which are a cell-specific target of and responsible for the cellular entry of novel coronavirus are localized in lipid rafts, agents that specifically disrupt the relevant rafts may be a drug against coronavirus disease 2019.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"14 ","pages":"34-47"},"PeriodicalIF":2.7,"publicationDate":"2020-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/0a/DTI-14-34.PMC7832984.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38872168","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: 17

Targeting Streptococcus pneumoniae UDP-glucose pyrophosphorylase (UGPase): in vitro validation of a putative inhibitor. 靶向肺炎链球菌udp -葡萄糖焦磷酸化酶(UGPase):一种推定抑制剂的体外验证。

IF 2.7 Q3 PHARMACOLOGY & PHARMACY

Drug Target Insights

Pub Date : 2020-10-07 eCollection Date: 2020-01-01 DOI: 10.33393/dti.2020.2103

Monica Sharma, Swati Sharma, Pallab Ray, Anuradha Chakraborti

Background: Genome plasticity of Streptococcus pneumoniae is responsible for the reduced efficacy of various antibiotics and capsular polysaccharide-based vaccines. Therefore, targets independent of capsular types are sought to control the pneumococcal pathogenicity. UDP-glucose pyrophosphorylase (UGPase) is one such desired candidate being responsible for the synthesis of UDP-glucose, a sugar precursor in capsular biosynthesis and metabolic Leloir pathway. Being crucial to pneumococcal pathobiology, the effect of UGPase inhibition on virulence was evaluated in vitro.

Methods: A putative inhibitor, uridine diphosphate (UDP), was evaluated for effective inhibitory concentration in S. pneumoniae and A549 cells, its efficacy and toxicity. The effect of UDP on adherence and phagocytosis was measured in human respiratory epithelial (A549 and HEp-2) and macrophage (THP1 and J774.A.1) cell lines respectively.

Results: A differential effective inhibitory concentration of UDP for UGPase inhibition was observed in S. pneumoniae and A549 cells, that is, 5 and 100 µM respectively. UDP treatments lowered percent cytotoxicity in pneumococcal-infected monolayers and didn't exert adverse effects on viabilities. S. pneumoniae adherence to host cells decreased significantly with UDP treatments. UDP induced the secretion of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and IL-8 and increased pneumococcal phagocytosis.

Conclusion: Our study shows UDP-mediated decrease in the virulence of S. pneumoniae and demonstrates UDP as an effective inhibitor of pneumococcal UGPase.

背景:肺炎链球菌的基因组可塑性是各种抗生素和荚膜多糖疫苗疗效降低的原因。因此，寻求独立于荚膜类型的靶点来控制肺炎球菌的致病性。udp -葡萄糖焦磷酸化酶(UGPase)就是其中一种需要的候选物，它负责合成udp -葡萄糖，这是包膜生物合成和代谢Leloir途径中的糖前体。作为肺炎球菌病理生物学的关键，我们在体外评估了UGPase抑制对毒力的影响。方法:研究一种推定的抑制剂尿苷二磷酸(UDP)对肺炎链球菌和A549细胞的有效抑制浓度、疗效和毒性。在人呼吸上皮(A549和HEp-2)和巨噬细胞(THP1和J774.A.1)细胞系中分别测定了UDP对粘附和吞噬的影响。结果:UDP在肺炎链球菌和A549细胞中对UGPase的有效抑制浓度不同，分别为5µM和100µM。UDP治疗降低了肺炎球菌感染单层细胞的细胞毒性百分比，并且对存活率没有不利影响。UDP治疗显著降低了肺炎链球菌对宿主细胞的粘附性。UDP诱导白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α、IL-6和IL-8的分泌，增加肺炎球菌的吞噬能力。结论:我们的研究显示UDP介导的肺炎链球菌毒力下降，并证明UDP是肺炎球菌UGPase的有效抑制剂。

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引用次数: 3

Paradoxical bronchoconstriction caused by β₂-adrenoceptor agonists. β2-肾上腺素能受体激动剂引起的矛盾性支气管收缩。

IF 2.7 Q3 PHARMACOLOGY & PHARMACY

Drug Target Insights

Pub Date : 2020-10-05 eCollection Date: 2020-01-01 DOI: 10.33393/dti.2020.2188

Khadija Ayed, Islam Latifa Hadj Khalifa, Salma Mokaddem, Saloua Ben Khamsa Jameleddine

Introduction: Salbutamol and terbutaline are short-acting β₂ adrenergic agonists that produce bronchial smooth muscle relaxation and are widely used in obstructive pulmonary diseases. Nevertheless, their use has been the cause of a paradoxical bronchoconstriction, which is a rare and potentially serious adverse reaction. The aim of this study is to report a case of paradoxical bronchoconstriction caused by β₂ adrenergic agonists.

Methods: This case is about a 50-year-old asthmatic patient who describes a history of repeated acute asthma attacks after salbutamol inhalation or terbutaline nebulization. A double-blind crossover study was performed over 3 days, in order to compare the effects of each bronchodilator. Forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and maximal expiratory flow 25-75 (MEF25-75) were measured.

Results: On the first day, a bronchoconstriction caused by deep and repeated inhalations was eliminated. On the second day, an airway obstruction was confirmed by a decrease in FEV₁ at 40% from baseline values after nebulization of a standard dose of terbutaline. On the third day, a spirometry was performed before and after nebulization of a standard dose of ipratropium bromide, and there were no significant changes in the spirometric parameters. Finally the patient was discharged with a written warning mentioning the danger of salbutamol and terbutaline use.

Conclusion: Salbutamol and terbutaline are generally well-tolerated β₂ adrenergic agonists. Nevertheless, in rare cases, these substances can cause a paradoxical bronchoconstriction. Doctors must therefore remain vigilant about its side effect and possibly investigate each case.

简介:沙丁胺醇和特布他林是短效β2肾上腺素能激动剂，可使支气管平滑肌松弛，广泛用于阻塞性肺疾病。然而，它们的使用引起了一种矛盾的支气管收缩，这是一种罕见的潜在严重的不良反应。本研究的目的是报告一例由β2肾上腺素能激动剂引起的矛盾性支气管收缩。方法:本病例是一位50岁左右的哮喘患者，在吸入沙丁胺醇或特布他林雾化后反复出现急性哮喘发作。为了比较每种支气管扩张剂的效果，进行了为期3天的双盲交叉研究。测定1秒用力呼气量(FEV1)、用力肺活量(FVC)、最大呼气流量25-75 (MEF25-75)。结果:第一天，反复深吸引起的支气管收缩消失。第二天，雾化标准剂量特布他林后，FEV1较基线值下降40%，证实气道阻塞。第3天，在雾化标准剂量异丙托溴铵前后进行肺活量测定，肺活量测定参数无明显变化。最后，患者出院时收到书面警告，告知使用沙丁胺醇和特布他林的危险。结论:沙丁胺醇和特布他林是耐受性良好的β2肾上腺素能激动剂。然而，在极少数情况下，这些物质可引起矛盾的支气管收缩。因此，医生必须对其副作用保持警惕，并可能对每个病例进行调查。

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引用次数: 4