ABSTRACT The world is under the great threat of antimicrobial resistance (AMR) leading to premature deaths. Microorganisms can produce AMR via quorum sensing mechanisms utilizing S-adenosyl homocysteine/methylthioadenosine nucleosidase (SAH/MTAN) biosynthesis. But there is no specific drug developed to date to stop SAH/MTAN, which is a crucial target for the discovery of anti-quorum sensing compound. It has been shown that indazole compounds cause inhibition of SAH/MTAN-mediated quorum sensing, but the biochemical mechanisms have not yet been explored. Therefore, in this original research, an attempt has been made to explore essential structural features of these compounds by quantitative structure-activity relationship (QSAR) and molecular docking of indazole compounds having inhibition of SAH/MTAN-mediated quorum sensing. The validated QSAR predicted five essential descriptors and molecular docking helps to identify the active binding amino acid residues involved in ligand-receptor interactions that are responsible for producing the quorum sensing inhibitory mechanisms of indazole compounds against SAH/MTAN-mediated AMR.
{"title":"Exploring the inhibitory mechanisms of indazole compounds against SAH/MTAN-mediated quorum sensing utilizing QSAR and docking.","authors":"Sisir Nandi, Mohit Kumar, Rashmi Kumari, Aaruni Saxena","doi":"10.33393/dti.2022.2512","DOIUrl":"https://doi.org/10.33393/dti.2022.2512","url":null,"abstract":"ABSTRACT The world is under the great threat of antimicrobial resistance (AMR) leading to premature deaths. Microorganisms can produce AMR via quorum sensing mechanisms utilizing S-adenosyl homocysteine/methylthioadenosine nucleosidase (SAH/MTAN) biosynthesis. But there is no specific drug developed to date to stop SAH/MTAN, which is a crucial target for the discovery of anti-quorum sensing compound. It has been shown that indazole compounds cause inhibition of SAH/MTAN-mediated quorum sensing, but the biochemical mechanisms have not yet been explored. Therefore, in this original research, an attempt has been made to explore essential structural features of these compounds by quantitative structure-activity relationship (QSAR) and molecular docking of indazole compounds having inhibition of SAH/MTAN-mediated quorum sensing. The validated QSAR predicted five essential descriptors and molecular docking helps to identify the active binding amino acid residues involved in ligand-receptor interactions that are responsible for producing the quorum sensing inhibitory mechanisms of indazole compounds against SAH/MTAN-mediated AMR.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":null,"pages":null},"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/b3/b6/dti-16-54.PMC9788832.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10459525","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}
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.
{"title":"MRSA carriage among healthcare workers in a Vietnamese intensive care unit: a prospective cohort study.","authors":"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","doi":"10.33393/dti.2022.2504","DOIUrl":"https://doi.org/10.33393/dti.2022.2504","url":null,"abstract":"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.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":null,"pages":null},"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/98/4b/dti-16-71.PMC9808530.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9076436","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}
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":null,"pages":null},"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}
Pub Date : 2021-11-27eCollection Date: 2021-01-01DOI: 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":null,"pages":null},"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}
Pub Date : 2021-11-08eCollection Date: 2021-01-01DOI: 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":null,"pages":null},"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}
Pub Date : 2021-04-02eCollection Date: 2021-01-01DOI: 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 (<i>Tamarindus indica</i> 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":null,"pages":null},"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}
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":null,"pages":null},"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}
Pub Date : 2020-12-22eCollection Date: 2020-01-01DOI: 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":null,"pages":null},"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}
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.
{"title":"Targeting <i>Streptococcus pneumoniae</i> UDP-glucose pyrophosphorylase (UGPase): in vitro validation of a putative inhibitor.","authors":"Monica Sharma, Swati Sharma, Pallab Ray, Anuradha Chakraborti","doi":"10.33393/dti.2020.2103","DOIUrl":"https://doi.org/10.33393/dti.2020.2103","url":null,"abstract":"<p><strong>Background: </strong>Genome plasticity of <i>Streptococcus pneumoniae</i> 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.</p><p><strong>Methods: </strong>A putative inhibitor, uridine diphosphate (UDP), was evaluated for effective inhibitory concentration in <i>S. pneumoniae</i> 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.</p><p><strong>Results: </strong>A differential effective inhibitory concentration of UDP for UGPase inhibition was observed in <i>S. pneumoniae</i> 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. <i>S. pneumoniae</i> 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.</p><p><strong>Conclusion: </strong>Our study shows UDP-mediated decrease in the virulence of <i>S. pneumoniae</i> and demonstrates UDP as an effective inhibitor of pneumococcal UGPase.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2020-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/4b/DTI-14-26.PMC7597228.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38553328","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}
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