Evidence for NUDT15 pharmacogenomic variants and thiopurine-induced myelosuppression (TIM), consists predominantly of association data in Asian, mixed variant homozygote/heterozygote populations. We therefore sought evidence on; NUDT15 genotype-guided thiopurine dosing Association data for TIM in NUDT15 variant heterozygotes with inflammatory bowel disease Association data for NUDT15 variants with TIM in Europeans Health economic data for NUDT15 genotyping in inflammatory bowel disease A systematic review was conducted, consisting of database searches, screening against pre-defined inclusion/exclusion criteria, and assessment of risk of bias using study-specific appraisal tools. Significant reductions in TIM with genotype-guided thiopurine dosing were reported by both trials and a cohort study TIM rates were significantly higher in NUDT15*3 heterozygotes versus wildtype. Data were conflicting for rarer variants. Four of five studies reported an association with TIM for at least one, or a combination of NUDT15 variants in Europeans (OR 9.5-38.2), but data were conflicting. Both health economic analyses found TPMT/NUDT15 genotyping cost effective in Asian populations, but not when a European population was considered. Limited data showed an association with TIM in NUDT15 variant heterozygotes and Europeans and the potential for genotype-guided dosing to reduce TIM. Studies were generally small, heterogenous and of variable quality. The low prevalence of rarer NUDT15 variants/variants in Europeans likely contributed to contradictory findings. Further research on the clinical utility of genotyping in diverse populations will help inform future economic analyses.
有关 NUDT15 药物基因组变异和硫嘌呤诱导的骨髓抑制 (TIM) 的证据主要包括亚洲混合变异同型/杂合子人群的关联数据。因此，我们寻求以下方面的证据：NUDT15 基因型指导的硫嘌呤剂量 NUDT15 变异杂合子炎症性肠病患者 TIM 的关联数据 欧洲人 NUDT15 变异与 TIM 的关联数据 NUDT15 基因分型治疗炎症性肠病的健康经济数据 我们进行了一项系统性综述，包括数据库检索、根据预先定义的纳入/排除标准进行筛选，以及使用特定研究评估工具对偏倚风险进行评估。 两项试验和一项队列研究均报告了在基因型指导下使用硫嘌呤剂量可显著降低TIM，NUDT15*3杂合子的TIM发生率显著高于野生型。关于罕见变异的数据则相互矛盾。五项研究中有四项报告了欧洲人中至少一种或多种 NUDT15 变异与 TIM 的关系（OR 9.5-38.2），但数据相互矛盾。两项健康经济分析均发现，在亚洲人群中进行 TPMT/NUDT15 基因分型具有成本效益，但在考虑欧洲人群时则不具成本效益。 有限的数据显示，NUDT15 变异杂合子和欧洲人的 TIM 与基因型指导用药有可能降低 TIM。这些研究通常规模较小、类型多样且质量参差不齐。欧洲人中较罕见的 NUDT15 变体/变异体的发病率较低，这可能是导致研究结果相互矛盾的原因之一。进一步研究基因分型在不同人群中的临床效用将有助于为未来的经济分析提供依据。
{"title":"A systematic review of aspects of NUDT15 pharmacogenomic variants and thiopurine-induced myelosuppression","authors":"Rachel Palmer, Jaime Peters","doi":"10.1093/rpsppr/rqae013","DOIUrl":"https://doi.org/10.1093/rpsppr/rqae013","url":null,"abstract":"\u0000 \u0000 \u0000 Evidence for NUDT15 pharmacogenomic variants and thiopurine-induced myelosuppression (TIM), consists predominantly of association data in Asian, mixed variant homozygote/heterozygote populations. We therefore sought evidence on;\u0000 NUDT15 genotype-guided thiopurine dosing\u0000 Association data for TIM in NUDT15 variant heterozygotes with inflammatory bowel disease\u0000 Association data for NUDT15 variants with TIM in Europeans\u0000 Health economic data for NUDT15 genotyping in inflammatory bowel disease\u0000 \u0000 \u0000 \u0000 A systematic review was conducted, consisting of database searches, screening against pre-defined inclusion/exclusion criteria, and assessment of risk of bias using study-specific appraisal tools.\u0000 \u0000 \u0000 \u0000 Significant reductions in TIM with genotype-guided thiopurine dosing were reported by both trials and a cohort study\u0000 TIM rates were significantly higher in NUDT15*3 heterozygotes versus wildtype. Data were conflicting for rarer variants.\u0000 Four of five studies reported an association with TIM for at least one, or a combination of NUDT15 variants in Europeans (OR 9.5-38.2), but data were conflicting.\u0000 Both health economic analyses found TPMT/NUDT15 genotyping cost effective in Asian populations, but not when a European population was considered.\u0000 \u0000 \u0000 \u0000 Limited data showed an association with TIM in NUDT15 variant heterozygotes and Europeans and the potential for genotype-guided dosing to reduce TIM. Studies were generally small, heterogenous and of variable quality. The low prevalence of rarer NUDT15 variants/variants in Europeans likely contributed to contradictory findings. Further research on the clinical utility of genotyping in diverse populations will help inform future economic analyses.\u0000","PeriodicalId":74744,"journal":{"name":"RPS pharmacy and pharmacology reports","volume":" 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141672684","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}
The current review summarizes product and process attributes that were reported to influence protein integrity during manufacturing and storage of dissolvable microneedle arrays. It also discusses challenges in employing established protein characterization methods in dissolvable microneedle formulations. Studies on dissolvable microneedles loaded with protein therapeutics that assess protein stability during or after fabrication and storage were collected. Publications addressing other types of microneedles, such as coated and vaccine-loaded microneedles, are also discussed as they face similar stability challenges. To date, various researchers have successfully incorporated proteins in dissolvable microneedles, but few publications explicitly investigated the impact of formulation and process parameters on protein stability. However, protein therapeutics are exposed to multiple thermal, physical, and chemical stressors during the fabrication and storage of microneedles. These stressors include increased temperature, shear and interfacial stress, transition to the solid state during drying, interaction with excipients, and suboptimal pH environments. While analytical methods are essential for monitoring protein integrity during manufacturing and storage, the performance of some well-established protein characterization techniques can be undermined by polymer excipients commonly employed in dissolvable microneedle formulations. It is essential to understand the impact of key process and formulation parameters on the stability of protein therapeutics to facilitate their safe and effective administration by dissolvable microneedles.
{"title":"Stress factors affecting protein stability during the fabrication and storage of dissolvable microneedles","authors":"Laura Koenitz, A. Crean, Sonja Vucen","doi":"10.1093/rpsppr/rqae018","DOIUrl":"https://doi.org/10.1093/rpsppr/rqae018","url":null,"abstract":"\u0000 \u0000 \u0000 The current review summarizes product and process attributes that were reported to influence protein integrity during manufacturing and storage of dissolvable microneedle arrays. It also discusses challenges in employing established protein characterization methods in dissolvable microneedle formulations.\u0000 \u0000 \u0000 \u0000 Studies on dissolvable microneedles loaded with protein therapeutics that assess protein stability during or after fabrication and storage were collected. Publications addressing other types of microneedles, such as coated and vaccine-loaded microneedles, are also discussed as they face similar stability challenges.\u0000 \u0000 \u0000 \u0000 To date, various researchers have successfully incorporated proteins in dissolvable microneedles, but few publications explicitly investigated the impact of formulation and process parameters on protein stability. However, protein therapeutics are exposed to multiple thermal, physical, and chemical stressors during the fabrication and storage of microneedles. These stressors include increased temperature, shear and interfacial stress, transition to the solid state during drying, interaction with excipients, and suboptimal pH environments. While analytical methods are essential for monitoring protein integrity during manufacturing and storage, the performance of some well-established protein characterization techniques can be undermined by polymer excipients commonly employed in dissolvable microneedle formulations.\u0000 \u0000 \u0000 \u0000 It is essential to understand the impact of key process and formulation parameters on the stability of protein therapeutics to facilitate their safe and effective administration by dissolvable microneedles.\u0000","PeriodicalId":74744,"journal":{"name":"RPS pharmacy and pharmacology reports","volume":"2018 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141706664","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}
Deepti Tiwari, Pushpa Kewlani, Laxman Singh, Sandeep Rawat, Indra D Bhatt, R. C. Sundriyal, Veena Pande
This review analyzed available literature on traditional/ ethnomedicinal knowledge, phytochemical composition, anticancer activities reported in vitro and in vivo studies, and the toxicological activity of Taraxacum officinale. The aim is to provide an in-depth analysis of existing research on the anticancer potential of T. officinale. The data was extracted using four search engines, Google Scholar, Web of Science, Scopus, and Pubmed, and systematically analyzed to identify effective plant-based substances for cancer treatment. The different parts of the plant are the source of different bioactive compounds that exhibit several pharmacological activities like antidiabetic, hepatoprotective, antimicrobial, anticancer, analgesic, etc. Traditionally, it is used to treat various ailments such as migraines, cardiac complaints, jaundice, fever, liver and kidney disorders, migraines, and hepatitis. Different biologically active compounds isolated from T. officinale are widely investigated against various pharmacological activities, including cancer. The available evidence on the bioactive potential of Taraxacum officinale provides direction for identifying and developing herbal agents to prevent different types of cancers in the future. However, there is a need to examine the clinical validation of pure compounds for drug development.
这篇综述分析了有关蒲公英（Taraxacum officinale）的传统/民族医药知识、植物化学成分、体外和体内抗癌活性以及毒理学活性的现有文献。本研究旨在深入分析现有的有关欧当归抗癌潜力的研究。 通过谷歌学术、Web of Science、Scopus 和 Pubmed 四个搜索引擎提取数据，并进行系统分析，以确定治疗癌症的有效植物性物质。该植物的不同部位是不同生物活性化合物的来源，这些化合物具有多种药理活性，如抗糖尿病、保肝、抗菌、抗癌、镇痛等。传统上，它被用来治疗各种疾病，如偏头痛、心脏病、黄疸、发烧、肝脏和肾脏疾病、偏头痛和肝炎。从 T. officinale 中分离出来的不同生物活性化合物被广泛用于研究各种药理作用，包括癌症。 有关蒲公英生物活性潜力的现有证据为今后确定和开发预防不同类型癌症的草药提供了方向。不过，还需要对纯化合物进行临床验证，以便进行药物开发。
{"title":"A review on natural bioactive compounds of Taraxacum officinale Weber: A potential anticancer plant","authors":"Deepti Tiwari, Pushpa Kewlani, Laxman Singh, Sandeep Rawat, Indra D Bhatt, R. C. Sundriyal, Veena Pande","doi":"10.1093/rpsppr/rqae009","DOIUrl":"https://doi.org/10.1093/rpsppr/rqae009","url":null,"abstract":"\u0000 \u0000 \u0000 This review analyzed available literature on traditional/ ethnomedicinal knowledge, phytochemical composition, anticancer activities reported in vitro and in vivo studies, and the toxicological activity of Taraxacum officinale. The aim is to provide an in-depth analysis of existing research on the anticancer potential of T. officinale.\u0000 \u0000 \u0000 \u0000 The data was extracted using four search engines, Google Scholar, Web of Science, Scopus, and Pubmed, and systematically analyzed to identify effective plant-based substances for cancer treatment. The different parts of the plant are the source of different bioactive compounds that exhibit several pharmacological activities like antidiabetic, hepatoprotective, antimicrobial, anticancer, analgesic, etc. Traditionally, it is used to treat various ailments such as migraines, cardiac complaints, jaundice, fever, liver and kidney disorders, migraines, and hepatitis. Different biologically active compounds isolated from T. officinale are widely investigated against various pharmacological activities, including cancer.\u0000 \u0000 \u0000 \u0000 The available evidence on the bioactive potential of Taraxacum officinale provides direction for identifying and developing herbal agents to prevent different types of cancers in the future. However, there is a need to examine the clinical validation of pure compounds for drug development.\u0000","PeriodicalId":74744,"journal":{"name":"RPS pharmacy and pharmacology reports","volume":" 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141371044","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}
There has been paucity of research reports on the obscured antidepressant mechanism of action for the atypical antipsychotics. The present study was designed to elucidate and unravel the novel antidepressant mechanism of action for the atypical antipsychotics. During the course of this present study, original peer-reviewed articles reported in English language that investigated atypical antipsychotics were identified by exploring the Medline-Entrez-PubMed search, Web of Science database, Google Scholar search, and Science Direct database online facilities. Information was also sourced from printed textbooks and the reports documented by some recognized medically inclined and health professional bodies. These published materials containing documented reports relating to the subject matter of focus in this review article were accessed and adequately referenced. This study spanned for 8-month duration from March 2023 to November 2023. A total number of 117 published articles were reviewed, out of which 61 referenced articles were found to contain information pertinent to this present study, while those parts of the referenced articles inapt to this study were neglected. Based on pharmacological mechanism of action, the atypical antipsychotic agents can be broadly classified into two major subclasses, namely: regular and irregular atypical antipsychotics. This review will proclaim and repurpose the atypical antipsychotics pharmacological properties for more comprehensive therapeutic usage as a new generation class of antidepressants that had brought forth substantial improvement and positive outcome to the management of patients with depressive disorders.
{"title":"Elucidating And Unravelling The Novel Antidepressant Mechanism Of Action For Atypical Antipsychotics: Repurposing The Atypical Antipsychotics For More Comprehensive Therapeutic Usage","authors":"O. Fasipe, Igbekele Ogunboye","doi":"10.1093/rpsppr/rqae017","DOIUrl":"https://doi.org/10.1093/rpsppr/rqae017","url":null,"abstract":"\u0000 \u0000 \u0000 There has been paucity of research reports on the obscured antidepressant mechanism of action for the atypical antipsychotics.\u0000 \u0000 \u0000 \u0000 The present study was designed to elucidate and unravel the novel antidepressant mechanism of action for the atypical antipsychotics.\u0000 \u0000 \u0000 \u0000 During the course of this present study, original peer-reviewed articles reported in English language that investigated atypical antipsychotics were identified by exploring the Medline-Entrez-PubMed search, Web of Science database, Google Scholar search, and Science Direct database online facilities. Information was also sourced from printed textbooks and the reports documented by some recognized medically inclined and health professional bodies. These published materials containing documented reports relating to the subject matter of focus in this review article were accessed and adequately referenced. This study spanned for 8-month duration from March 2023 to November 2023.\u0000 \u0000 \u0000 \u0000 A total number of 117 published articles were reviewed, out of which 61 referenced articles were found to contain information pertinent to this present study, while those parts of the referenced articles inapt to this study were neglected. Based on pharmacological mechanism of action, the atypical antipsychotic agents can be broadly classified into two major subclasses, namely: regular and irregular atypical antipsychotics.\u0000 \u0000 \u0000 \u0000 This review will proclaim and repurpose the atypical antipsychotics pharmacological properties for more comprehensive therapeutic usage as a new generation class of antidepressants that had brought forth substantial improvement and positive outcome to the management of patients with depressive disorders.\u0000","PeriodicalId":74744,"journal":{"name":"RPS pharmacy and pharmacology reports","volume":"71 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141268323","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}
Ayurvedic manuscripts describe five distinct techniques to purify sulfur, each designed to improve its purity, quality, and effectiveness. The complexity of these methods emphasizes the importance of being meticulous in ensuring the purification of sulfur, which is a crucial step in maintaining the high standards of quality and safety that are integral the herbo mineral formulations in Ayurveda medicine. The study was conducted to document the technological modifications implemented by Ayurvedic pharmaceutics to purify sulfur. A convenient sampling methodology was utilized for the selection of study sites. The study included pharmaceutical companies that employ mechanized processes. An in-depth interview was conducted with the production manager at each site, using a semi-structured questionnaire consisting of three domains. Four pharmaceutical companies that use mechanized processes were selected for a survey. These companies have innovatively applied the traditional melting and pouring (Dhalana) process to purify significant amounts of sulfur with the help of machines. The quantity of sulfur being purified varied among the selected companies, ranging from 5 kg to 150 kg. Implementing appropriate optimization techniques can enhance the efficiency of mechanized manufacturing processes. Collaborating with interdisciplinary sectors is crucial to devise more effective mechanization solutions.
{"title":"“Exploratory Study to Document Large-Scale Sulfur Purification in Ayurveda Pharmaceutics”","authors":"Anjana C S, Harisankar D, Anand S, Galib R","doi":"10.1093/rpsppr/rqae008","DOIUrl":"https://doi.org/10.1093/rpsppr/rqae008","url":null,"abstract":"\u0000 \u0000 \u0000 Ayurvedic manuscripts describe five distinct techniques to purify sulfur, each designed to improve its purity, quality, and effectiveness. The complexity of these methods emphasizes the importance of being meticulous in ensuring the purification of sulfur, which is a crucial step in maintaining the high standards of quality and safety that are integral the herbo mineral formulations in Ayurveda medicine.\u0000 \u0000 \u0000 \u0000 The study was conducted to document the technological modifications implemented by Ayurvedic pharmaceutics to purify sulfur.\u0000 \u0000 \u0000 \u0000 A convenient sampling methodology was utilized for the selection of study sites. The study included pharmaceutical companies that employ mechanized processes. An in-depth interview was conducted with the production manager at each site, using a semi-structured questionnaire consisting of three domains.\u0000 \u0000 \u0000 \u0000 Four pharmaceutical companies that use mechanized processes were selected for a survey. These companies have innovatively applied the traditional melting and pouring (Dhalana) process to purify significant amounts of sulfur with the help of machines. The quantity of sulfur being purified varied among the selected companies, ranging from 5 kg to 150 kg.\u0000 \u0000 \u0000 \u0000 Implementing appropriate optimization techniques can enhance the efficiency of mechanized manufacturing processes. Collaborating with interdisciplinary sectors is crucial to devise more effective mechanization solutions.\u0000","PeriodicalId":74744,"journal":{"name":"RPS pharmacy and pharmacology reports","volume":"15 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141107640","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}
Rannod R Vandyarto, Aaron P Domingues, Richard G Cornwall
In order to better understand hydroxychavicol’s effectiveness as an oral antibacterial, its structural components were analyzed with respect to minimum inhibitory concentrations and minimum bactericidal concentrations against various oral bacteria. These structural components include the free hydroxy groups and allyl chain connected to hydroxychavicol’s benzene core. Six structural analogs of hydroxychavicol were tested against a range of oral bacteria using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. MIC results were obtained using serial microdilution techniques in 96-well plates with resazurin dye as a colorimetric indicator. Aliquots within each MIC concentration range were then placed on appropriate agar medium and the minimum bactericidal concentration was determined as the lowest concentration with no observed colony growth. A synergistic interaction was observed between the allyl chain and hydroxy groups on the benzene core of hydroxychavicol, which resulted in lower MICs against the tested oral bacteria. It was also found that a hydroxy group para to the allyl chain on the benzene ring resulted in more effective inhibition, with a MIC of <50 μg/mL against R. dentocariosa. Additionally, analytes possessing free hydroxy groups ortho to one another on the benzene ring resulted in MICs of 200-300 μg/mL or lower, whereas analytes with free hydroxy groups meta to one another on the benzene ring exhibited MICs of >1000 μg/mL. This study helps elucidate the structural components responsible for hydroxychavicol’s effectiveness as an oral antibacterial. The findings herein help to understand the mechanism of hydroxychavicol’s antibacterial properties and will be helpful in the design and synthesis of more effective oral antibacterial treatments.
为了更好地了解羟基黄烷醇作为口腔抗菌剂的功效，我们分析了其结构成分对各种口腔细菌的最小抑菌浓度和最小杀菌浓度。这些结构成分包括游离羟基和与羟基茶维醇苯核相连的烯丙基链。 我们使用最低抑菌浓度 (MIC) 和最低杀菌浓度 (MBC) 法测试了羟基黄烷醇的六种结构类似物对一系列口腔细菌的作用。在 96 孔板中使用序列微量稀释技术得出 MIC 结果，并以瑞舒灵染料作为比色指示剂。然后将每个 MIC 浓度范围内的等分试样置于适当的琼脂培养基上，以未观察到菌落生长的最低浓度为最小杀菌浓度。 研究发现，烯丙基链与羟基茶维素苯核上的羟基之间存在协同作用，从而降低了对受测口腔细菌的 MIC 值。研究还发现，羟基与苯环上的烯丙基链对位可产生更有效的抑制作用，其 MIC 值为 1000 μg/mL。 这项研究有助于阐明羟基茶维醇作为口服抗菌剂有效的结构成分。本文的研究结果有助于了解羟基黄烷醇的抗菌机制，并将有助于设计和合成更有效的口服抗菌药。
{"title":"Analysis of the Molecular Structure of Hydroxychavicol, a Promising Oral Antibacterial","authors":"Rannod R Vandyarto, Aaron P Domingues, Richard G Cornwall","doi":"10.1093/rpsppr/rqae010","DOIUrl":"https://doi.org/10.1093/rpsppr/rqae010","url":null,"abstract":"\u0000 \u0000 \u0000 In order to better understand hydroxychavicol’s effectiveness as an oral antibacterial, its structural components were analyzed with respect to minimum inhibitory concentrations and minimum bactericidal concentrations against various oral bacteria. These structural components include the free hydroxy groups and allyl chain connected to hydroxychavicol’s benzene core.\u0000 \u0000 \u0000 \u0000 Six structural analogs of hydroxychavicol were tested against a range of oral bacteria using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. MIC results were obtained using serial microdilution techniques in 96-well plates with resazurin dye as a colorimetric indicator. Aliquots within each MIC concentration range were then placed on appropriate agar medium and the minimum bactericidal concentration was determined as the lowest concentration with no observed colony growth.\u0000 \u0000 \u0000 \u0000 A synergistic interaction was observed between the allyl chain and hydroxy groups on the benzene core of hydroxychavicol, which resulted in lower MICs against the tested oral bacteria. It was also found that a hydroxy group para to the allyl chain on the benzene ring resulted in more effective inhibition, with a MIC of <50 μg/mL against R. dentocariosa. Additionally, analytes possessing free hydroxy groups ortho to one another on the benzene ring resulted in MICs of 200-300 μg/mL or lower, whereas analytes with free hydroxy groups meta to one another on the benzene ring exhibited MICs of >1000 μg/mL.\u0000 \u0000 \u0000 \u0000 This study helps elucidate the structural components responsible for hydroxychavicol’s effectiveness as an oral antibacterial. The findings herein help to understand the mechanism of hydroxychavicol’s antibacterial properties and will be helpful in the design and synthesis of more effective oral antibacterial treatments.\u0000","PeriodicalId":74744,"journal":{"name":"RPS pharmacy and pharmacology reports","volume":"105 44","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141124723","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}
Huilong Tan, Yanfei Li, Fangjun Lv, Xianliang Zeng, Shuangying Wang
PHN, a common sequela of herpes zoster, is a significant health concern, especially among the elderly. It is estimated that approximately 65% of patients above 60 years old develop PHN, and up to 75% of individuals with herpes zoster over 70 years old may develop PHN. While several drugs have been found effective, the numbers needed to treat for these drugs is over 6. Many patients still experience inadequate pain relief. Combination therapy is often considered when adequate pain relief is not achieved. Gabapentin is sometimes combined with pregabalin for PHN treatment and this therapy is not recommended by relevant treatment guidelines. We conducted a retrospective analysis of medical records of PHN patients who received combination therapy with gabapentin and pregabalin at our hospital. Data collected included numeric rating scale (NRS) pain scores before and after combination therapy, as well as the duration of each therapy. Statistical analysis was performed using SPSS software. A total of 15 patients were included in this study. The mean NRS score before combination therapy was 4.40±1.35, which decreased significantly to 2.20±1.30 post-treatment (p=0.001). The duration of combination therapy was comparable to that of monotherapy. One patient reported adverse reactions following the switch to combination therapy. For PHN patients who do not respond adequately to monotherapy, combining gabapentin and pregabalin is a viable option. However, larger studies with randomized controlled trials are needed to further validate the finding.
{"title":"Combination therapy of Gabapentin and Pregabalin for Postherpetic Neuralgia in 15 Patients","authors":"Huilong Tan, Yanfei Li, Fangjun Lv, Xianliang Zeng, Shuangying Wang","doi":"10.1093/rpsppr/rqae006","DOIUrl":"https://doi.org/10.1093/rpsppr/rqae006","url":null,"abstract":"\u0000 \u0000 \u0000 PHN, a common sequela of herpes zoster, is a significant health concern, especially among the elderly. It is estimated that approximately 65% of patients above 60 years old develop PHN, and up to 75% of individuals with herpes zoster over 70 years old may develop PHN. While several drugs have been found effective, the numbers needed to treat for these drugs is over 6. Many patients still experience inadequate pain relief. Combination therapy is often considered when adequate pain relief is not achieved. Gabapentin is sometimes combined with pregabalin for PHN treatment and this therapy is not recommended by relevant treatment guidelines.\u0000 \u0000 \u0000 \u0000 We conducted a retrospective analysis of medical records of PHN patients who received combination therapy with gabapentin and pregabalin at our hospital. Data collected included numeric rating scale (NRS) pain scores before and after combination therapy, as well as the duration of each therapy. Statistical analysis was performed using SPSS software.\u0000 \u0000 \u0000 \u0000 A total of 15 patients were included in this study. The mean NRS score before combination therapy was 4.40±1.35, which decreased significantly to 2.20±1.30 post-treatment (p=0.001). The duration of combination therapy was comparable to that of monotherapy. One patient reported adverse reactions following the switch to combination therapy.\u0000 \u0000 \u0000 \u0000 For PHN patients who do not respond adequately to monotherapy, combining gabapentin and pregabalin is a viable option. However, larger studies with randomized controlled trials are needed to further validate the finding.\u0000","PeriodicalId":74744,"journal":{"name":"RPS pharmacy and pharmacology reports","volume":" 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140210736","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}
Highly drug-loaded polymer formulations are favorable intermediates in pharmaceutical applications for example for the individualized production of medicines via 3D printing with the maximum flexibility regarding dose strength and drug combination in a single dosage form. However, high disperse drug loads are challenging for the process itself and the (intermediate) product properties, making the knowledge about the dispersion state of the drug particles achieved by the production process helpful to overcome such challenges. Therefore, a novel dispersion state analysis technique based on scanning Raman microscopy is proposed in the present study and applied to HPMC filaments loaded with 20 wt.%, 40 wt.% and 60 wt.% theophylline. The qualitative and quantitative evaluations of the scans were correlated to melt viscosities, process data and mechanical properties of the filaments. The analyses revealed not only an increasing particle size reduction with increasing drug load and thus increasing viscosity and mechanical energy input. The particle size reduction also caused a change of the filaments’ mechanical properties from elastic ductile to rigid brittle. Furthermore, an alignment of the elongate drug particles with the frozen three-dimensional flow pattern of the extruder and not only with the extrusion direction was elucidated. Therefore, the necessity to investigate the dispersion state further is highlighted for future studies on highly drug-loaded polymer formulations, providing a novel measuring technique applicable for challenging pharmaceutical formulations.
{"title":"Dispersion state analysis in hot melt extruded, highly drug-loaded 3D printing filaments applying Raman-microscopy","authors":"Marius Tidau, J. Finke","doi":"10.1093/rpsppr/rqae007","DOIUrl":"https://doi.org/10.1093/rpsppr/rqae007","url":null,"abstract":"\u0000 \u0000 \u0000 Highly drug-loaded polymer formulations are favorable intermediates in pharmaceutical applications for example for the individualized production of medicines via 3D printing with the maximum flexibility regarding dose strength and drug combination in a single dosage form. However, high disperse drug loads are challenging for the process itself and the (intermediate) product properties, making the knowledge about the dispersion state of the drug particles achieved by the production process helpful to overcome such challenges.\u0000 \u0000 \u0000 \u0000 Therefore, a novel dispersion state analysis technique based on scanning Raman microscopy is proposed in the present study and applied to HPMC filaments loaded with 20 wt.%, 40 wt.% and 60 wt.% theophylline. The qualitative and quantitative evaluations of the scans were correlated to melt viscosities, process data and mechanical properties of the filaments.\u0000 \u0000 \u0000 \u0000 The analyses revealed not only an increasing particle size reduction with increasing drug load and thus increasing viscosity and mechanical energy input. The particle size reduction also caused a change of the filaments’ mechanical properties from elastic ductile to rigid brittle. Furthermore, an alignment of the elongate drug particles with the frozen three-dimensional flow pattern of the extruder and not only with the extrusion direction was elucidated.\u0000 \u0000 \u0000 \u0000 Therefore, the necessity to investigate the dispersion state further is highlighted for future studies on highly drug-loaded polymer formulations, providing a novel measuring technique applicable for challenging pharmaceutical formulations.\u0000","PeriodicalId":74744,"journal":{"name":"RPS pharmacy and pharmacology reports","volume":" 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140220536","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}
Prawej Ansari, Joyeeta T Khan, Mousume Soultana, Lauren Hunter, Suraiya Chowdhury, Suriya K Priyanka, Saikat R Paul, PETER R. Flatt, Y. Abdel-Wahab
Momordica charantia, commonly known as bitter gourd, is traditionally used as remedies for various diseases including diabetes. The main objective of this study is to investigate the in vitro and in vivo insulinotropic and anti-diabetic effects of an 80% ethanolic extract of Momordica charantia (EEMC) fruit, as well as the underlying molecular mechanism involved and preliminary phytochemical screening. The insulin secretion was measured using clonal pancreatic BRIN-BD11 β-cells and isolated mouse islets. The ability of EEMC to inhibit carbohydrate digestive enzymes and glucose absorption and, scavenge free radicals were assessed via starch digestion, glucose diffusion and DPPH assay methods. The effects of EEMC on a variety of metabolic parameters were evaluated in alloxan-induced type 2 diabetic rats, including lipid profile. Finally, a preliminary phytochemical screening was conducted to identify the active phytoconstituents. EEMC increased insulin release through the KATP-dependent/cAMP pathway, which depolarizes the β-cell membrane and elevates intracellular calcium. It also inhibited glucose absorption and free radicals, suggesting its potential to delay gastric emptying, attenuate oxidative stress, and reduce inflammatory cytokines. In vivo studies showed that EEMC improves oral glucose tolerance, food intake, fasting blood glucose, plasma insulin, lipids, and promotes intestinal motility. The active phytoconstituents in EEMC, such as flavonoids, alkaloids, tannins, saponins, steroids, and glycosides, are likely responsible for these effects. The antihyperglycemic properties of EEMC indicate that it might be a promising candidate for diabetes management. However, additional study into the application of Momordica charantia in type 2 diabetes is essential.
{"title":"Insulin secretory actions of polyphenols of Momordica charantia regulate glucose homeostasis in alloxan-induced type 2 diabetic rats","authors":"Prawej Ansari, Joyeeta T Khan, Mousume Soultana, Lauren Hunter, Suraiya Chowdhury, Suriya K Priyanka, Saikat R Paul, PETER R. Flatt, Y. Abdel-Wahab","doi":"10.1093/rpsppr/rqae005","DOIUrl":"https://doi.org/10.1093/rpsppr/rqae005","url":null,"abstract":"\u0000 \u0000 \u0000 Momordica charantia, commonly known as bitter gourd, is traditionally used as remedies for various diseases including diabetes. The main objective of this study is to investigate the in vitro and in vivo insulinotropic and anti-diabetic effects of an 80% ethanolic extract of Momordica charantia (EEMC) fruit, as well as the underlying molecular mechanism involved and preliminary phytochemical screening.\u0000 \u0000 \u0000 \u0000 The insulin secretion was measured using clonal pancreatic BRIN-BD11 β-cells and isolated mouse islets. The ability of EEMC to inhibit carbohydrate digestive enzymes and glucose absorption and, scavenge free radicals were assessed via starch digestion, glucose diffusion and DPPH assay methods. The effects of EEMC on a variety of metabolic parameters were evaluated in alloxan-induced type 2 diabetic rats, including lipid profile. Finally, a preliminary phytochemical screening was conducted to identify the active phytoconstituents.\u0000 \u0000 \u0000 \u0000 EEMC increased insulin release through the KATP-dependent/cAMP pathway, which depolarizes the β-cell membrane and elevates intracellular calcium. It also inhibited glucose absorption and free radicals, suggesting its potential to delay gastric emptying, attenuate oxidative stress, and reduce inflammatory cytokines. In vivo studies showed that EEMC improves oral glucose tolerance, food intake, fasting blood glucose, plasma insulin, lipids, and promotes intestinal motility. The active phytoconstituents in EEMC, such as flavonoids, alkaloids, tannins, saponins, steroids, and glycosides, are likely responsible for these effects.\u0000 \u0000 \u0000 \u0000 The antihyperglycemic properties of EEMC indicate that it might be a promising candidate for diabetes management. However, additional study into the application of Momordica charantia in type 2 diabetes is essential.\u0000","PeriodicalId":74744,"journal":{"name":"RPS pharmacy and pharmacology reports","volume":"14 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140082007","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}
I. Abubakar, I. Malami, Aliyu Muhamamd, Tijjani Salihu Shinkafi, Dayyabu Shehu, Patrick MaduabuchiAja
Piliostigma thonningii is a medicinal plant commonly found in Eastern and Western Africa with a potential traditional usage to treat various diseases. Several studies have revealed interesting pharmacological activities of the plant and different phytochemicals were identified. This study critically reviewed the medicinal uses, phytochemistry, and bioactivity of P. thonningii. Relevant databases including ISI Web of Knowledge, Science Direct, Scopus, PubMed, and Google Scholar as well as databases for theses were searched for information using the keyword P. thonningii and its synonym. P. thonningii is majorly prepared in Africa as a decoction, infusion, maceration, and ointment and administered orally or topically to treat several diseases such as malaria, cancer, hepatitis, diabetes, and others. Pharmacological studies have demonstrated activities including antimalarial, antiviral, antimicrobial, anti-proliferative, and other medicinal properties. Compounds including piliostigmin, C-methyl flavonols, quercetin, and others were among the active components. The general use of P. thonnigii in various medicinal forms in Africa presents a great opportunity for the development of innovative research toward the production of natural products and nutraceuticals. Nevertheless, additional studies especially in vivo are necessary to further elucidate the mechanism mediating the bioactivities, especially in relation to the medicinal and nutritional uses.
Piliostigma thonningii 是一种常见于非洲东部和西部的药用植物，具有治疗各种疾病的潜在传统用途。多项研究揭示了该植物有趣的药理活性，并发现了不同的植物化学物质。本研究对 P. thonningii 的药用、植物化学和生物活性进行了严格审查。 使用关键词 P. thonningii 及其同义词搜索了相关数据库，包括 ISI Web of Knowledge、Science Direct、Scopus、PubMed 和 Google Scholar 以及论文数据库。 在非洲，P. thonningii 主要被制成煎剂、注射剂、浸渍剂和软膏剂，口服或外用可治疗多种疾病，如疟疾、癌症、肝炎、糖尿病等。药理研究表明，它具有抗疟、抗病毒、抗菌、抗增殖和其他药用特性。其活性成分包括 piliostigmin、C-甲基黄酮醇、槲皮素等化合物。 在非洲，P. thonnigii 以各种药用形式被广泛使用，这为天然产品和营养保健品生产方面的创新研究提供了巨大的发展机遇。不过，有必要进行更多的研究，特别是体内研究，以进一步阐明生物活性的介导机制，尤其是与药用和营养用途有关的机制。
{"title":"A review of the medicinal uses and biological activities of Piliostigma thonningii (Schum). Milne-Redh","authors":"I. Abubakar, I. Malami, Aliyu Muhamamd, Tijjani Salihu Shinkafi, Dayyabu Shehu, Patrick MaduabuchiAja","doi":"10.1093/rpsppr/rqae004","DOIUrl":"https://doi.org/10.1093/rpsppr/rqae004","url":null,"abstract":"\u0000 \u0000 \u0000 Piliostigma thonningii is a medicinal plant commonly found in Eastern and Western Africa with a potential traditional usage to treat various diseases. Several studies have revealed interesting pharmacological activities of the plant and different phytochemicals were identified. This study critically reviewed the medicinal uses, phytochemistry, and bioactivity of P. thonningii.\u0000 \u0000 \u0000 \u0000 Relevant databases including ISI Web of Knowledge, Science Direct, Scopus, PubMed, and Google Scholar as well as databases for theses were searched for information using the keyword P. thonningii and its synonym.\u0000 \u0000 \u0000 \u0000 P. thonningii is majorly prepared in Africa as a decoction, infusion, maceration, and ointment and administered orally or topically to treat several diseases such as malaria, cancer, hepatitis, diabetes, and others. Pharmacological studies have demonstrated activities including antimalarial, antiviral, antimicrobial, anti-proliferative, and other medicinal properties. Compounds including piliostigmin, C-methyl flavonols, quercetin, and others were among the active components.\u0000 \u0000 \u0000 \u0000 The general use of P. thonnigii in various medicinal forms in Africa presents a great opportunity for the development of innovative research toward the production of natural products and nutraceuticals. Nevertheless, additional studies especially in vivo are necessary to further elucidate the mechanism mediating the bioactivities, especially in relation to the medicinal and nutritional uses.\u0000","PeriodicalId":74744,"journal":{"name":"RPS pharmacy and pharmacology reports","volume":" 47","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139787928","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}
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