Current drug safety最新文献

筛选
英文 中文
Evaluation of High-dose versus Standard-dose of Dexamethasone on Mortality among the Mechanically Ventilated COVID-19 Patients. 评估大剂量与标准剂量地塞米松对机械通气 COVID-19 患者死亡率的影响
IF 1.1
Current drug safety Pub Date : 2024-01-01 DOI: 10.2174/1574886318666230817102043
Pramodini B Kale-Pradhan, Regina Pacitto, Christopher A Giuliano, Leonard B Johnson
{"title":"Evaluation of High-dose <i>versus</i> Standard-dose of Dexamethasone on Mortality among the Mechanically Ventilated COVID-19 Patients.","authors":"Pramodini B Kale-Pradhan, Regina Pacitto, Christopher A Giuliano, Leonard B Johnson","doi":"10.2174/1574886318666230817102043","DOIUrl":"10.2174/1574886318666230817102043","url":null,"abstract":"<p><strong>Introduction: </strong>Anti-inflammatory agents like dexamethasone (DEX) are a mainstay of treatment for COVID-19. Despite randomized trials demonstrating that a 6 mg daily dose of DEX improved patient outcomes in hospitalized COVID-19 patients receiving oxygen, clinicians often prescribe higher doses of corticosteroids without evidence to support this practice. The purpose of this study was to compare outcomes of ventilated COVID-19 patients who received standard dose (SD) versus high dose (HD) DEX.</p><p><strong>Methods: </strong>This was a multi-site, retrospective, observational study on ventilated COVID-19- positive patients who received DEX for at least three days between June 1, 2020, and January 31, 2022. The primary outcome of this study was the association between mortality and SD (<6 mg daily) versus HD (>10 mg daily) DEX in ventilated COVID-19 patients. Secondary outcomes included average blood glucose (BG), number of BG readings above 200, incidence of bacterial nosocomial infection, ventilator-free days, length of stay (LOS), and ICU LOS.</p><p><strong>Results: </strong>Of the 212 included patients, 53 (25%) received SD DEX, and 159 (75%) received HD DEX. There was no significant effect of DEX dose on mortality, number of BG readings >200, incidence of nosocomial infections, LOS, or ventilator-free days (p >0.05). After controlling for confounding factors, no difference in mortality persisted (OR 1.34 95% CI 0.62- 2.90). Average daily BG and ICU LOS were significantly greater in the HD group compared to the SD group (p = 0.003, p = 0.019, respectively).</p><p><strong>Conclusion: </strong>There was no association between HD DEX and mortality among ventilated COVID- 19 patients compared to SD DEX. Moreover, HD DEX is associated with detrimental effects such as prolonged ICU LOS and higher average daily BG. This study supports the use of SD DEX in ventilated COVID-19 patients.</p>","PeriodicalId":10777,"journal":{"name":"Current drug safety","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10078106","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
Cyclophosphamide Toxicity in Pediatric Nephrotic Syndrome Patient: A Case Report and Literature Review. 小儿肾病综合征患者的环磷酰胺毒性:病例报告和文献综述。
IF 1.1
Current drug safety Pub Date : 2024-01-01 DOI: 10.2174/0115748863281214231213075642
Soumya Patil, Mahantesh V Patil, Apoorva Bagalkotkar, Shashikala Wali
{"title":"Cyclophosphamide Toxicity in Pediatric Nephrotic Syndrome Patient: A Case Report and Literature Review.","authors":"Soumya Patil, Mahantesh V Patil, Apoorva Bagalkotkar, Shashikala Wali","doi":"10.2174/0115748863281214231213075642","DOIUrl":"10.2174/0115748863281214231213075642","url":null,"abstract":"<p><strong>Background: </strong>Primary membranous nephropathy is a rare presentation in children. Patients unresponsive to steroids and experiencing frequent relapse are considered steroid-resistant. They often require complex treatment regimens consisting of immunosuppressants like cyclophosphamide, tacrolimus, and cyclosporin A.</p><p><strong>Case: </strong>In the present case, a 5-year-old child was suffering from steroid-resistant nephrotic syndrome for the past 10 months. He was initially treated with prednisolone 20mg but was subsequently found to be steroid-resistant. A renal biopsy revealed primary podocytopathy with immunocomplex deposits in podocyte tissues, suggesting primary membranous nephropathy as the cause of SRNS (steroid-resistant nephrotic syndrome). Cyclophosphamide 25mg twice daily was added to the treatment plan since the child did not tolerate tacrolimus therapy. During a subsequent follow-up, the physician reduced the cyclophosphamide 25mg dose to once a day, but parents misinterpreted this, and the child received a larger dose, cyclophosphamide 25mg, four times a day for 20 days. This resulted in cyclophosphamide toxicity-induced neutropenia, alopecia and posing the child at greater risk of sepsis.</p><p><strong>Conclusion: </strong>Nephrotic syndrome is a chronic disease that demands extensive treatment plans and strict monitoring. Medication errors are common among parents or caregivers of pediatric patients. This case is a take-home message emphasizing the significance of patient-centered communication in preventing medication errors. A clinical pharmacist can aid in conveying simple and unambiguous information to parents or caregivers.</p>","PeriodicalId":10777,"journal":{"name":"Current drug safety","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416592","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
Antidepressant-induced Paradoxical Anxiety, Akathisia, and Complex Vocal Tics in a Patient with Panic Disorder and Crohn's Disease: A Case Report. 一名患有恐慌症和克罗恩病的患者因抗抑郁药诱发的矛盾焦虑、肌痉挛和复杂发声抽搐:病例报告。
IF 1.1
Current drug safety Pub Date : 2024-01-01 DOI: 10.2174/0115748863270093231114075934
Azriel H K Koh, Soon Shan Loh, Leslie Lim
{"title":"Antidepressant-induced Paradoxical Anxiety, Akathisia, and Complex Vocal Tics in a Patient with Panic Disorder and Crohn's Disease: A Case Report.","authors":"Azriel H K Koh, Soon Shan Loh, Leslie Lim","doi":"10.2174/0115748863270093231114075934","DOIUrl":"10.2174/0115748863270093231114075934","url":null,"abstract":"<p><strong>Background: </strong>Antidepressant-induced paradoxical anxiety is a fairly common phenomenon seen in patients who are initiated on antidepressants. However, akathisia is a very uncommon manifestation of antidepressants. Much more rarely, antidepressants are also associated with the emergence of motor and vocal tics. This case adds to the growing literature of rare adverse events induced by antidepressants and aims to stimulate future research into the mechanism and risk factors of this phenomenon.</p><p><strong>Case presentation: </strong>In this case report, we describe a patient with panic disorder and co-morbid Crohn's disease who developed worsening anxiety, akathisia and vocal tics upon initiation of fluvoxamine. This is the first case report to describe the emergence of both akathisia and vocal tics in the same patient following antidepressant initiation. After discontinuation of fluvoxamine, the patient's symptoms resolved.</p><p><strong>Conclusion: </strong>Antidepressant-induced akathisia and tics are often distressing both to the patient and their loved ones, and can be very puzzling to the clinician. It is important for clinicians to recognise that, although rare, antidepressants can adverse effects. When these symptoms arise, it should prompt immediate discontinuation of the offending antidepressant.</p>","PeriodicalId":10777,"journal":{"name":"Current drug safety","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512052","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
Tumor Necrosis Alpha (TNF-α) Antagonists Used in Chronic Inflammatory Rheumatic Diseases: Risks and their Minimization Measures. 用于慢性炎症性风湿病的肿瘤坏死α(TNF-α)拮抗剂:风险及其最小化措施。
IF 1.1
Current drug safety Pub Date : 2024-01-01 DOI: 10.2174/0115748863274863231222023853
Rim Lakhmiri, Yahia Cherrah, Samira Serragui
{"title":"Tumor Necrosis Alpha (TNF-α) Antagonists Used in Chronic Inflammatory Rheumatic Diseases: Risks and their Minimization Measures.","authors":"Rim Lakhmiri, Yahia Cherrah, Samira Serragui","doi":"10.2174/0115748863274863231222023853","DOIUrl":"10.2174/0115748863274863231222023853","url":null,"abstract":"<p><p>Tumor necrosis factor alpha (TNF- α) inhibitors are widely employed for the management of chronic inflammatory rheumatism. However, their usage carries significant risks, including site and infusion reactions, serious infections, malignancy, heart failure autoimmune and demyelinating disorders. These risks are comprehensively outlined in risk management plans (RMPs) associated with these molecules. RMP provides information on the safety profile of a medicinal product as well as the measures that will be taken to minimize risks; these are known as risk minimization measures. These measures are divided into routine measures related to elements, such as the summary of product characteristics, labeling, pack size, package leaflet, or legal supply status of the product, while additional measures may include educational programs, including tools for healthcare providers and patients, controlled access or pregnancy prevention programs, among others. Additional measures can consist of one or more interventions that need to be implemented in a sustainable way in a defined target group, while respecting the timing and frequency of any intervention and procedures to reach the target population. An evaluation of the effectiveness of these measures is required to determine whether or not an intervention has been effective. This comprehensive review offers an in-depth exploration of the current treatment, uses, and associated risks of TNF-α inhibitors. Additionally, it provides a detailed account of risk minimization measures and risk management practices while shedding light on their real-world implementation and effectiveness.</p>","PeriodicalId":10777,"journal":{"name":"Current drug safety","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416596","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
A Case Report of Cefixime, Paracetamol, and Nimesulide Induced Toxic Epidermal Necrolysis in a Woman with Dengue Infection without any Other Associated Comorbidities. 一名登革热感染妇女因头孢克肟、扑热息痛和尼美舒利诱发中毒性表皮坏死症的病例报告,该妇女无任何其他相关并发症。
IF 1.5
Current drug safety Pub Date : 2024-01-01 DOI: 10.2174/1574886318666230418104445
Renuka Munshi, Miteshkumar Maurya
{"title":"A Case Report of Cefixime, Paracetamol, and Nimesulide Induced Toxic Epidermal Necrolysis in a Woman with Dengue Infection without any Other Associated Comorbidities.","authors":"Renuka Munshi, Miteshkumar Maurya","doi":"10.2174/1574886318666230418104445","DOIUrl":"10.2174/1574886318666230418104445","url":null,"abstract":"<p><strong>Background: </strong>Toxic Epidermal Necrolysis (TEN) is a rare, acute, and life-threatening mucocutaneous disease that occurs after the administration of certain drugs, resulting in extensive keratinocyte cell death, skin involvement at the dermal-epidermal junction, and extensive bullous skin eruptions and sloughing. Many published case reports have observed the presence of fever with a viral infection, drug, and/or genetic association as a possible trigger for TEN but associated with other comorbidities. Physicians still struggle to predict which individuals could be predisposed to TEN. The case report that we present had a history of multiple drug intake and fever due to dengue virus infection but was not associated with any other comorbidity.</p><p><strong>Case presentation: </strong>We present an unusual case of a 32-year-old woman of Western Indian origin who had developed dengue infection and suffered toxic epidermal necrolysis following a five-day course of a third-generation cephalosporin antibiotic, cefixime and a three-day course of 2 analgesic drugs, paracetamol (acetaminophen), and nimesulide, with the adverse event occurring on the fifth day of the dengue infection. The offending drugs were stopped, and patient survived with supportive management and hydration.</p><p><strong>Conclusion: </strong>The presence of comorbidities may not always be the triggering factor for TEN, though it can affect patient outcomes. Rational drug use is always recommended for patient care. Further research is required to understand the pathomechanism behind the viral-drug-gene interaction.</p>","PeriodicalId":10777,"journal":{"name":"Current drug safety","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9420436","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
Association of Cardiovascular Events with COVID-19 Vaccines Using Vaccine Adverse Event Reporting System (VAERS): A Retrospective Study. 使用疫苗不良事件报告系统(VAERS)的心血管事件与COVID-19疫苗的关联:一项回顾性研究
IF 1.1
Current drug safety Pub Date : 2024-01-01 DOI: 10.2174/0115748863276904231108095255
Mohd Amir, S Latha, Ruchika Sharma, Anoop Kumar
{"title":"Association of Cardiovascular Events with COVID-19 Vaccines Using Vaccine Adverse Event Reporting System (VAERS): A Retrospective Study.","authors":"Mohd Amir, S Latha, Ruchika Sharma, Anoop Kumar","doi":"10.2174/0115748863276904231108095255","DOIUrl":"10.2174/0115748863276904231108095255","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 vaccines have played a crucial role in reducing the burden of the global pandemic. However, recent case reports have indicated the association of the COVID- 19 vaccines with cardiovascular events but the exact association is unclear so far.</p><p><strong>Objective: </strong>Therefore, the objective of the current study is to find out the association of cardiovascular events with COVID-19 vaccines.</p><p><strong>Methods: </strong>The COVID-19 Vaccine Knowledge Base (Cov19VaxKB) tool was used to query the Vaccine Adverse Event Reporting System (VAERS) database. The proportional reporting ratio [PRR (≥2)] with associated chi-squared value (>4), and the number of cases > 0.2% of total reports, was used to assess the association of COVID-19 vaccines with cardiovascular events.</p><p><strong>Results: </strong>A total of 33,754 cases of cardiovascular events associated with COVID-19 vaccines were found in the Cov19VaxKB tool. The cases were observed in different age groups (18-64, and 65 years and above) and gender. The disproportionality measures indicate a statistically significant association between cardiovascular events and COVID-19 vaccines.</p><p><strong>Conclusion: </strong>The current study identified a signal of various cardiovascular events with the COVID-19 vaccines. However, further causality assessment is required to confirm the association.</p>","PeriodicalId":10777,"journal":{"name":"Current drug safety","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458400","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
A Review of Drug Abuse, Misuse, and Related Laboratory Challenges. 药物滥用、误用和相关实验室挑战综述。
IF 1.1
Current drug safety Pub Date : 2024-01-01 DOI: 10.2174/0115748863266621231023112044
Haniye Ranjkeshzadeh, Samaneh Sepahi, Hadi Zare-Zardini, Mohammad Ehsan Taghavizadeh Yazdi, Adel Ghorani-Azam, Abbas Jafari
{"title":"A Review of Drug Abuse, Misuse, and Related Laboratory Challenges.","authors":"Haniye Ranjkeshzadeh, Samaneh Sepahi, Hadi Zare-Zardini, Mohammad Ehsan Taghavizadeh Yazdi, Adel Ghorani-Azam, Abbas Jafari","doi":"10.2174/0115748863266621231023112044","DOIUrl":"10.2174/0115748863266621231023112044","url":null,"abstract":"<p><p>Various definitions can be considered for drugs and substance abuse. According to the National Institute on Abuse, the use of an over-the-counter drug in a different way than that prescribed to experience or arouse emotion is a simple form of drug abuse. The World Health Organization (WHO) also defines drug abuse as the persistent or sporadic use of drugs that are incompatible or unrelated to acceptable medical practice. With the increasing non-therapeutic use of prescription drugs, serious related consequences have also increased. Therefore, there is a need to know more precisely about the types of substances and drug abuse, which is the most important part of diagnosis and recognizing the tests that cause false positive and negative results. The purpose of this review article is to collect and summarize the most important and more common types of drugs of abuse and review the drugs that cause false results in screening tests. In addition, the most common detection methods of the drug will be reviewed and the advantages and drawbacks of each method will be discussed. In this article, we aimed to point out all the facts about the emerging problems in drug abuse, the methods of screening, and the possible false results in addition to troubleshooting strategies.</p>","PeriodicalId":10777,"journal":{"name":"Current drug safety","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92153083","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
The Effect of Renal Replacement Therapy in a Patient with Mercaptopurine Toxicity: Time to Revise Guidelines. 肾脏替代疗法对巯嘌呤中毒患者的影响:是时候修订指南了
IF 1.5
Current drug safety Pub Date : 2024-01-01 DOI: 10.2174/1574886318666230714105801
H J L Quaedvlieg, F N Polderman, M Borkent, De H J M Jonge, P A Annema, L J J Derijks, M A Sikma, C Bethlehem
{"title":"The Effect of Renal Replacement Therapy in a Patient with Mercaptopurine Toxicity: Time to Revise Guidelines.","authors":"H J L Quaedvlieg, F N Polderman, M Borkent, De H J M Jonge, P A Annema, L J J Derijks, M A Sikma, C Bethlehem","doi":"10.2174/1574886318666230714105801","DOIUrl":"10.2174/1574886318666230714105801","url":null,"abstract":"<p><strong>Introduction: </strong>Mercaptopurine, a thiopurine, is used in various disorders of immune regulation, such as autoimmune hepatitis. Thiopurine metabolism is complex with risk for overdosing, especially when metabolism is impaired by liver dysfunction. Hepatotoxicity may be due to mercaptopurine overdose and is often reversible after prompt cessation of the drug.</p><p><strong>Case presentation: </strong>Treatment of thiopurine toxicity is mainly supportive and literature on enhanced elimination by renal replacement therapy is ambiguous.</p><p><strong>Conclusion: </strong>In this case of thiopurine toxicity, a patient with autoimmune hepatitis presents with abdominal pain, nausea, vomiting, and diarrhea. We show in this case report that renal replacement therapy had no effect on total body clearance of mercaptopurine.</p>","PeriodicalId":10777,"journal":{"name":"Current drug safety","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9778353","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
Concise Review on Scientific Approaches to Burns and Scars. 烧伤和疤痕科学方法简明综述》。
IF 1.5
Current drug safety Pub Date : 2024-01-01 DOI: 10.2174/1574886318666230509143017
Hitesh Malhotra, Prerna Sharma, Mohammad Amjad Kamal, Peeyush Kaushik, Nidhi Rani
{"title":"Concise Review on Scientific Approaches to Burns and Scars.","authors":"Hitesh Malhotra, Prerna Sharma, Mohammad Amjad Kamal, Peeyush Kaushik, Nidhi Rani","doi":"10.2174/1574886318666230509143017","DOIUrl":"10.2174/1574886318666230509143017","url":null,"abstract":"<p><p>Burns are large open surgical lesions bathed in virulent pus that result in rupturing of the cutaneous membrane, which has serious consequences such as an extensive loss of proteins, and body fluids, increased chances of infections, and sometimes death. These can be classified based on their penetration levels, i.e., first-degree burns penetrating the epidermis, second-degree burns including both epidermis and dermis, third-degree burns to both layers including the hair follicular cells, sweat glands and various core tissues, fourth-degree burns to adipose tissue, fifth stage burns to muscles, and sixth stage burns to bones. Wound healing/wound repair is a very perplexing process in which the tissues of the affected/burnt area repairs themselves to attain their original form and functionality but develop a scar at the wound site. This article mainly focuses on the algorithms to differentiate various degrees of burns, general first aid approaches to burns and scars, the rationale of treatment of burns, basic mechanisms highlighting the healing processes in humans in terms of free from scar formation as well as with scar formation at their elementary levels including cellular as well as biochemical levels, utility, and progression of pre-clinical data to humans and finally approaches for the improvement of scar formation in man.</p>","PeriodicalId":10777,"journal":{"name":"Current drug safety","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796493","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
Interactions Between Antimicrobial Peptides and Targets Responsible for their Nephrotoxic Action: Molecular Dynamics Simulations. 抗菌肽与肾毒性作用靶点之间的相互作用:分子动力学模拟。
IF 1.1
Current drug safety Pub Date : 2024-01-01 DOI: 10.2174/1574886318666230905100924
Yury Lisnyak, Artur Martynov, Boris Farber
{"title":"Interactions Between Antimicrobial Peptides and Targets Responsible for their Nephrotoxic Action: Molecular Dynamics Simulations.","authors":"Yury Lisnyak, Artur Martynov, Boris Farber","doi":"10.2174/1574886318666230905100924","DOIUrl":"10.2174/1574886318666230905100924","url":null,"abstract":"<p><strong>Objectives: </strong>Polymyxin is the last line of defense against resistant forms of microorganisms, but it has significant nephrotoxicity. One of the directions in reducing the nephrotoxicity of polymyxin is to modify the charge of the molecule and accordingly, to change the topicity of the polymyxin derivative to the renal megalin. Such modification can lead to a decrease in the accumulation of polymyxin in the kidneys and reduce its toxicity while maintaining its antimicrobial properties. The study aimed to investigate the structural aspects of polymyxin nephrotoxicity at the atomic level to promote the more purposeful development of the polymyxin's derivatives with the lower nephrotoxic action.</p><p><strong>Materials and methods: </strong>The molecular dynamics simulations of the complexes of polymyxin B and its derivative NAB7061 (that carries only three positive charges located within the macrocycle) with megalin were performed in program package YASARA structure with explicit water (TIP3P) and ions (0.9 % NaCl) in NPT ensemble using the AMRER03 force field. After 10 ns equilibration, each system was simulated at 298 K and pH 7.4 for a 25 ns production phase. Simulations were run twice for each molecular system.</p><p><strong>Results: </strong>By molecular dynamics simulations, the possibility was shown for polymyxin to form a stable complex with two neighbor structural domains of megalin in accord with the universal mechanism of binding the cationic ligands by ligand-binding CR repeats of the LDLR-family receptors. It was reported that interactions of megalin with polymyxin were stronger than with its derivative having no positively charged groups outside the macrocycle. The structural prerequisites of these differences were revealed, explaining the less nephrotoxicity of such derivatives compared to polymyxin.</p><p><strong>Conclusion: </strong>Comparative molecular dynamics simulations of megalin interactions with polymyxin B and its derivative NAB7061, which carries no positive charges outside the macrocycle, revealed the possible structural prerequisites for the lower nephrotoxic action of such polymyxin derivatives. The weakening of polymyxins binding with megalin may become an effective preventive measure against polymyxin-induced nephrotoxicity.</p>","PeriodicalId":10777,"journal":{"name":"Current drug safety","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10153047","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信