Murtala Akanji Abdullahi, Elijah Oladapo Oyinloye, Akinyinka Alabi, Aderonke Adeyinka Aderinola, Luqman Opeyemi Ogunjimi, Adesina A Omoloye, Ayobami A Odusote, Joseph O Olusola, Oluwatosin O Adebayo, Wasiu Eniola Olooto
Objectives: Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study.
Methods: Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods.
Results: The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible.
Conclusions: The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.
{"title":"Toxicological evaluation of hydroethanol leaf extract of <i>Pupalia lappacea</i> (Linn.) Juss. (Amaranthaceae) in rodents.","authors":"Murtala Akanji Abdullahi, Elijah Oladapo Oyinloye, Akinyinka Alabi, Aderonke Adeyinka Aderinola, Luqman Opeyemi Ogunjimi, Adesina A Omoloye, Ayobami A Odusote, Joseph O Olusola, Oluwatosin O Adebayo, Wasiu Eniola Olooto","doi":"10.1515/dmpt-2021-0115","DOIUrl":"https://doi.org/10.1515/dmpt-2021-0115","url":null,"abstract":"<p><strong>Objectives: </strong>Several studies have established the ethnobotanical benefits of <i>Pupalia lappacea</i> (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of <i>P. lappacea</i> in rodents was carried out in this study.</p><p><strong>Methods: </strong>Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods.</p><p><strong>Results: </strong>The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible.</p><p><strong>Conclusions: </strong>The findings showed that <i>P. lappacea</i> is relatively safe at lower doses but cautions should be taken at higher dose.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40268878","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}
Objectives: To determine the impacts of missed phenobarbital (PB) doses on its pharmacokinetics and to investigate the appropriate replacement dosing scheme for various PB missed dose scenarios.
Methods: Monte Carlo simulations were performed using parameters from the selected population pharmacokinetic study. The impacts of missed PB dose and the proper replacement dosing scheme were assessed based on the percent deviation of simulated concentrations outside the reference range from the full adherence scenario.
Results: The impact of missed PB dose on its concentrations depended on the daily dose. The replacement with a respective regular dose and one and a half regular dose was appropriate for the one and two missed doses scenarios for patients receiving PB monotherapy. For patients receiving PB with valproic acid or phenytoin, the same replacement scheme was still appropriate. The results also indicated that weight did not influence the proper replacement dosing scheme.
Conclusions: The impacts of missed PB doses on its pharmacokinetics were identified and the proper replacement dosing schemes for different missed dose scenarios were proposed. These schemes should be implemented based on the clinician's justification of the patient's seizure control.
{"title":"The effect of nonadherence on phenobarbital concentrations and recommendations on the replacement dose using Monte Carlo simulation.","authors":"Janthima Methaneethorn","doi":"10.1515/dmdi-2022-0104","DOIUrl":"10.1515/dmdi-2022-0104","url":null,"abstract":"<p><strong>Objectives: </strong>To determine the impacts of missed phenobarbital (PB) doses on its pharmacokinetics and to investigate the appropriate replacement dosing scheme for various PB missed dose scenarios.</p><p><strong>Methods: </strong>Monte Carlo simulations were performed using parameters from the selected population pharmacokinetic study. The impacts of missed PB dose and the proper replacement dosing scheme were assessed based on the percent deviation of simulated concentrations outside the reference range from the full adherence scenario.</p><p><strong>Results: </strong>The impact of missed PB dose on its concentrations depended on the daily dose. The replacement with a respective regular dose and one and a half regular dose was appropriate for the one and two missed doses scenarios for patients receiving PB monotherapy. For patients receiving PB with valproic acid or phenytoin, the same replacement scheme was still appropriate. The results also indicated that weight did not influence the proper replacement dosing scheme.</p><p><strong>Conclusions: </strong>The impacts of missed PB doses on its pharmacokinetics were identified and the proper replacement dosing schemes for different missed dose scenarios were proposed. These schemes should be implemented based on the clinician's justification of the patient's seizure control.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88703670","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}
W. A. Baig, Kholoud Alwosaibai, K. M. Al-Jubran, T. Chaudhry, Nouf Al-Dowish, Fatimah A. Alsaffar, Md Anzar Alam
Abstract Objectives Breast cancer is the most commonly diagnosed invasive non-skin malignancy in women worldwide, and it is the leading cause of cancer-related deaths in them. Nigella sativa Linn. seed oil has been found to be effective in cancer treatment as well as having anti-cancer properties in some other types of cancers. The study looked into the synergistic cytotoxic effects of N. sativa Linn. seed oil and doxorubicin in the treatment of human breast cancer cells (MCF-7). Methods Nigella sativa Linn. seed oil was used to evaluate its effect on human breast cancer cells, either alone or in conjunction with doxorubicin. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests were used to examine cell proliferation and cell viability, while phase-contrast inverted microscopy was used to examine cellular morphology. Furthermore, the role of N. sativa seed oil in decreasing cell tumorigenicity features was highlighted by testing the cancer cell migration using the wound healing assay. Results Results showed that higher concentrations (50 μg/mL) of N. sativa Linn. seed oil changed the breast cancer cell morphology and decreased the cell proliferation and viability. Breast cancer cells treated with black seed oil decreased cell movement after 24 hours compared to the untreated cell in the wound healing assay. Whereas, only the higher concentration of doxorubicin (0.5–2.5 μg/mL) reduced cell proliferation and cell viability. Moreover, the combination treatment of 50 μg/mL of black seed oil with different concentrations of doxorubicin caused a significant cell proliferation reduction and decreased cell viability. The activity was seen optimum at lower concentration (0.1 µg/mL) of doxorubicin. Conclusions There was decreased cell proliferation and cell viability when N. sativa seed oil was used alone or in conjunction with doxorubicin in Breast cancer cells (MCF-7) revealing potential opportunities in the field of cancer treatment.
{"title":"Synergistic anti-cancer effects of Nigella sativa seed oil and conventional cytotoxic agent against human breast cancer","authors":"W. A. Baig, Kholoud Alwosaibai, K. M. Al-Jubran, T. Chaudhry, Nouf Al-Dowish, Fatimah A. Alsaffar, Md Anzar Alam","doi":"10.1515/dmpt-2021-0229","DOIUrl":"https://doi.org/10.1515/dmpt-2021-0229","url":null,"abstract":"Abstract Objectives Breast cancer is the most commonly diagnosed invasive non-skin malignancy in women worldwide, and it is the leading cause of cancer-related deaths in them. Nigella sativa Linn. seed oil has been found to be effective in cancer treatment as well as having anti-cancer properties in some other types of cancers. The study looked into the synergistic cytotoxic effects of N. sativa Linn. seed oil and doxorubicin in the treatment of human breast cancer cells (MCF-7). Methods Nigella sativa Linn. seed oil was used to evaluate its effect on human breast cancer cells, either alone or in conjunction with doxorubicin. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests were used to examine cell proliferation and cell viability, while phase-contrast inverted microscopy was used to examine cellular morphology. Furthermore, the role of N. sativa seed oil in decreasing cell tumorigenicity features was highlighted by testing the cancer cell migration using the wound healing assay. Results Results showed that higher concentrations (50 μg/mL) of N. sativa Linn. seed oil changed the breast cancer cell morphology and decreased the cell proliferation and viability. Breast cancer cells treated with black seed oil decreased cell movement after 24 hours compared to the untreated cell in the wound healing assay. Whereas, only the higher concentration of doxorubicin (0.5–2.5 μg/mL) reduced cell proliferation and cell viability. Moreover, the combination treatment of 50 μg/mL of black seed oil with different concentrations of doxorubicin caused a significant cell proliferation reduction and decreased cell viability. The activity was seen optimum at lower concentration (0.1 µg/mL) of doxorubicin. Conclusions There was decreased cell proliferation and cell viability when N. sativa seed oil was used alone or in conjunction with doxorubicin in Breast cancer cells (MCF-7) revealing potential opportunities in the field of cancer treatment.","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82193975","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}
Jasmine Holail, Reem Mobarak, Bandar Al-Ghamdi, Ahmad Aljada, Hana Fakhoury
Objectives: Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in VKORC1 and CYP2C9 genes could influence warfarin therapy. Herein, we investigated whether VKORC1 -1173C>T, CYP2C9*2, and CYP2C9*3 gene polymorphisms are associated with warfarin dose adjustment and related bleeding events.
Methods: This cross-sectional study was conducted on Saudi adults receiving warfarin for more than 1 month. Their demographics and relevant clinical data were obtained. Genotyping for VKORC1 -1173C>T, CYP2C9*2, and CYP2C9*2 genotypes was performed.
Results: Patients who are homozygous for the mutant T allele VKORC1 T/T required the lowest warfarin daily maintenance dose, compared to VKORC1 C/T and VKORC1 C/C. Similarly, there was a significant reduction in warfarin daily maintenance dose among CYP2C9*1/*3 and CYP2C9*1/*2 groups compared to CYP2C9*1/*1. However, we found no significant correlation between the studied polymorphisms and warfarin-associated bleeding.
Conclusions: Similar to other populations, the VKORC1 and CYP2C9 gene polymorphisms are significantly associated with warfarin dosage in Saudi patients. The presence of at least one copy of the mutant alleles for VKORC1 -1173C>T, CYP2C9*2, and CYP2C9*3 is associated with a significant reduction in warfarin maintenance dose.
{"title":"Association of <i>VKORC1</i> and <i>CYP2C9</i> single-nucleotide polymorphisms with warfarin dose adjustment in Saudi patients.","authors":"Jasmine Holail, Reem Mobarak, Bandar Al-Ghamdi, Ahmad Aljada, Hana Fakhoury","doi":"10.1515/dmdi-2022-0108","DOIUrl":"10.1515/dmdi-2022-0108","url":null,"abstract":"<p><strong>Objectives: </strong>Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in <i>VKORC1</i> and <i>CYP2C9</i> genes could influence warfarin therapy. Herein, we investigated whether <i>VKORC1</i> -1173C>T, <i>CYP2C9*2</i>, and <i>CYP2C9*3</i> gene polymorphisms are associated with warfarin dose adjustment and related bleeding events.</p><p><strong>Methods: </strong>This cross-sectional study was conducted on Saudi adults receiving warfarin for more than 1 month. Their demographics and relevant clinical data were obtained. Genotyping for <i>VKORC1</i> -1173C>T, <i>CYP2C9*2</i>, and <i>CYP2C9*2</i> genotypes was performed.</p><p><strong>Results: </strong>Patients who are homozygous for the mutant T allele <i>VKORC1</i> T/T required the lowest warfarin daily maintenance dose, compared to <i>VKORC1</i> C/T and <i>VKORC1</i> C/C. Similarly, there was a significant reduction in warfarin daily maintenance dose among <i>CYP2C9*1/*3</i> and <i>CYP2C9*1/*2</i> groups compared to <i>CYP2C9*1/*1</i>. However, we found no significant correlation between the studied polymorphisms and warfarin-associated bleeding.</p><p><strong>Conclusions: </strong>Similar to other populations, the <i>VKORC1</i> and <i>CYP2C9</i> gene polymorphisms are significantly associated with warfarin dosage in Saudi patients. The presence of at least one copy of the mutant alleles for <i>VKORC1</i> -1173C>T, <i>CYP2C9*2</i>, and <i>CYP2C9*3</i> is associated with a significant reduction in warfarin maintenance dose.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76434992","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}
Charalampia Ioannou, G. Ragia, I. Balgkouranidou, N. Xenidis, K. Amarantidis, T. Koukaki, E. Biziota, S. Kakolyris, V. Manolopoulos
Abstract Objectives The fluoropyrimidine derivatives 5-Fluorouracil and Capecitabine are widely used for the treatment of solid tumors. Fluoropyrimidine metabolism involves a cascade of different enzymes, including MTHFR enzyme. MTHFR c.665C>T polymorphism, leading to decreased MTHFR activity, is a potential pharmacogenomic marker for fluoropyrimidine drug response. The aim of the present study was to analyze the association of MTHFR c.665C>T polymorphism with fluoropyrimidine response in terms of therapy induced adverse events (AEs), requirement of dose reduction and delayed drug administration or therapy discontinuation. Methods The study group consisted of 313 fluoropyrimidine-treated cancer patients. PCR-RFLP was used to analyze MTHFR c.665C>T polymorphism. Results In female patients, MTHFR c.665 CT and TT genotypes were associated with dose reduction (p=0.029). In gender stratification, regression analysis adjusted for age of disease onset, body surface area and AE incidence, showed that MTHFR CT and TT genotypes increased both need for fluoropyrimidine dose reduction (OR 5.050, 95% CI 1.346–18.948, p=0.016) and percentage of dose reduction (β=3.318, 95% C.I. 1.056–5.580, p=0.004) in female patients. Such differences were not present in male patients. No other associations were found. Conclusions MTHFR c.665C>T polymorphism was associated with fluoropyrimidine dose reduction in female cancer patients. This gender*MTHFR interaction merits further investigation.
摘要目的氟嘧啶衍生物5-氟尿嘧啶和卡培他滨被广泛用于实体瘤的治疗。氟嘧啶代谢涉及一系列不同的酶，包括MTHFR酶。MTHFR c.665C>T多态性导致MTHFR活性降低，是氟嘧啶药物反应的潜在药物基因组学标志物。本研究的目的是分析MTHFR c.665C>T多态性与氟嘧啶反应在治疗引起的不良事件(ae)、减量要求和延迟给药或停药方面的关系。方法以313例氟嘧啶治疗的肿瘤患者为研究对象。PCR-RFLP分析MTHFR c.665C>T多态性。结果女性患者中MTHFR为c.665CT和TT基因型与剂量减少相关(p=0.029)。在性别分层中，校正发病年龄、体表面积和AE发生率的回归分析显示，MTHFR CT和TT基因型女性患者氟嘧啶减剂量需求(OR 5.050, 95% CI 1.346 ~ 18.948, p=0.016)和减剂量百分比(β=3.318, 95% CI 1.056 ~ 5.580, p=0.004)均增加。这种差异在男性患者中不存在。没有发现其他关联。结论MTHFR c.665C>T多态性与女性肿瘤患者氟嘧啶剂量减少有关。这种性别*MTHFR的相互作用值得进一步研究。
{"title":"MTHFR c.665C>T guided fluoropyrimidine therapy in cancer: gender-dependent effect on dose requirements","authors":"Charalampia Ioannou, G. Ragia, I. Balgkouranidou, N. Xenidis, K. Amarantidis, T. Koukaki, E. Biziota, S. Kakolyris, V. Manolopoulos","doi":"10.1515/dmpt-2021-0219","DOIUrl":"https://doi.org/10.1515/dmpt-2021-0219","url":null,"abstract":"Abstract Objectives The fluoropyrimidine derivatives 5-Fluorouracil and Capecitabine are widely used for the treatment of solid tumors. Fluoropyrimidine metabolism involves a cascade of different enzymes, including MTHFR enzyme. MTHFR c.665C>T polymorphism, leading to decreased MTHFR activity, is a potential pharmacogenomic marker for fluoropyrimidine drug response. The aim of the present study was to analyze the association of MTHFR c.665C>T polymorphism with fluoropyrimidine response in terms of therapy induced adverse events (AEs), requirement of dose reduction and delayed drug administration or therapy discontinuation. Methods The study group consisted of 313 fluoropyrimidine-treated cancer patients. PCR-RFLP was used to analyze MTHFR c.665C>T polymorphism. Results In female patients, MTHFR c.665 CT and TT genotypes were associated with dose reduction (p=0.029). In gender stratification, regression analysis adjusted for age of disease onset, body surface area and AE incidence, showed that MTHFR CT and TT genotypes increased both need for fluoropyrimidine dose reduction (OR 5.050, 95% CI 1.346–18.948, p=0.016) and percentage of dose reduction (β=3.318, 95% C.I. 1.056–5.580, p=0.004) in female patients. Such differences were not present in male patients. No other associations were found. Conclusions MTHFR c.665C>T polymorphism was associated with fluoropyrimidine dose reduction in female cancer patients. This gender*MTHFR interaction merits further investigation.","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90252811","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}
A. Beletić, Aleksandra Tijanić, P. Chrastina, T. Nikolić, A. Stefanović, S. Stanković
Abstract Objectives The newborn screening (NBS) program in the Republic of Serbia has several decades of tradition, but it has not included any organic acidemias (OA). Therefore, this study aimed to establish the cut-offs of the corresponding NBS markers in the population of healthy newborns. Methods In dried blood samples (DBS) collected from 1,771 healthy newborns, we analyzed levels of propionylcarnitine (C3), isovalerylcarnitine (C5), and glutarylcarnitine (C5DC) using tandem mass spectrometry. Further we calculated the following ratios: C3/acetylcarnitine (C3/C2), C3/palmitoylcarnitine (C3/C16), C5/ free carnitine (C0), C5/C2, C5/C3, C5DC/octanoylcarnitine (C8), and C5DC/C0. Results The cut-offs for methylmalonic acidemia (MMA) or propionic acidemia (PA) were C3>5.73 μmol/L, C3/C2>0.23, and C3/C16>2.36. Based on the study findings, the screening results indicative for isovaleric acidemia (IVA) would include C5>0.372 μmol/L, C5/C0>0.020, C5/C2>0.019, and C5/C3>0.31. Finally, C5DC>0.303 μmol/L, C5DC/C8>7.1, and C5DC/C0>0.019 would justify further testing for glutaric acidemia type I (GA1). The cut-offs were satisfactorily validated via the comparison with worldwide estimates and data for several Caucasian populations. Conclusions The levels of the OA biomarkers in the Serbian population of healthy newborns have a distribution pattern similar to the other world populations. Therefore, the proposed cut-offs represent a reliable starting point for the future development of the OA NBS.
{"title":"The markers of the organic acidemias and their ratios in healthy neonates in Serbian population","authors":"A. Beletić, Aleksandra Tijanić, P. Chrastina, T. Nikolić, A. Stefanović, S. Stanković","doi":"10.1515/dmpt-2021-0218","DOIUrl":"https://doi.org/10.1515/dmpt-2021-0218","url":null,"abstract":"Abstract Objectives The newborn screening (NBS) program in the Republic of Serbia has several decades of tradition, but it has not included any organic acidemias (OA). Therefore, this study aimed to establish the cut-offs of the corresponding NBS markers in the population of healthy newborns. Methods In dried blood samples (DBS) collected from 1,771 healthy newborns, we analyzed levels of propionylcarnitine (C3), isovalerylcarnitine (C5), and glutarylcarnitine (C5DC) using tandem mass spectrometry. Further we calculated the following ratios: C3/acetylcarnitine (C3/C2), C3/palmitoylcarnitine (C3/C16), C5/ free carnitine (C0), C5/C2, C5/C3, C5DC/octanoylcarnitine (C8), and C5DC/C0. Results The cut-offs for methylmalonic acidemia (MMA) or propionic acidemia (PA) were C3>5.73 μmol/L, C3/C2>0.23, and C3/C16>2.36. Based on the study findings, the screening results indicative for isovaleric acidemia (IVA) would include C5>0.372 μmol/L, C5/C0>0.020, C5/C2>0.019, and C5/C3>0.31. Finally, C5DC>0.303 μmol/L, C5DC/C8>7.1, and C5DC/C0>0.019 would justify further testing for glutaric acidemia type I (GA1). The cut-offs were satisfactorily validated via the comparison with worldwide estimates and data for several Caucasian populations. Conclusions The levels of the OA biomarkers in the Serbian population of healthy newborns have a distribution pattern similar to the other world populations. Therefore, the proposed cut-offs represent a reliable starting point for the future development of the OA NBS.","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85417081","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}
Rachel A. Crane, Emery S. Grubb, L. Coward, G. Gorman
Abstract Objectives Colorectal cancer continues to have one of the highest incidents of occurrence with a rising rate of diagnosis among people under the age of 50. Chemotherapy with irinotecan results in severe gastrointestinal dose-limiting toxicity that is caused by the glucuronidated form of the active metabolite (SN-38G). This study evaluates herbal compounds and analogs to biomodulate the metabolism of IR to decrease dose-limiting toxicity while increasing the amount of the active metabolite. Methods In vitro metabolism using human liver microsomes was conducted with white willow bark (WWB) extract, select specific components of WWB, and analogues to evaluate biomodulation of the IR metabolism. Samples were analyzed using liquid chromatography-tandem mass spectrometry to measure metabolites between reactions with and without herbals components. Results WWB showed an optimal decrease (>80%) in SN-38G and a corresponding increase in SN-38 levels (128%) at a concentration of near 200 μg/mL. Tannic acid produced a 75% decrease in SN-38G with a 130% increase in SN-38 at 10 μg/mL, whereas the treatment with beta-pentagalloyl glucose and various analogues decreased SN-38G by 70% and increased SN-38 by 20% at 10 μg/mL. Conclusions These results suggest naturally occurring compounds from WWB may have the potential to increase potency by increasing the conversion of IR to SN-38 and decrease dose-limiting toxicity of IR chemotherapy by reducing glucuronidation of SN-38.
{"title":"In vitro metabolic biomodulation of irinotecan to increase potency and reduce dose-limiting toxicity by inhibition of SN-38 glucuronide formation","authors":"Rachel A. Crane, Emery S. Grubb, L. Coward, G. Gorman","doi":"10.1515/dmpt-2021-0178","DOIUrl":"https://doi.org/10.1515/dmpt-2021-0178","url":null,"abstract":"Abstract Objectives Colorectal cancer continues to have one of the highest incidents of occurrence with a rising rate of diagnosis among people under the age of 50. Chemotherapy with irinotecan results in severe gastrointestinal dose-limiting toxicity that is caused by the glucuronidated form of the active metabolite (SN-38G). This study evaluates herbal compounds and analogs to biomodulate the metabolism of IR to decrease dose-limiting toxicity while increasing the amount of the active metabolite. Methods In vitro metabolism using human liver microsomes was conducted with white willow bark (WWB) extract, select specific components of WWB, and analogues to evaluate biomodulation of the IR metabolism. Samples were analyzed using liquid chromatography-tandem mass spectrometry to measure metabolites between reactions with and without herbals components. Results WWB showed an optimal decrease (>80%) in SN-38G and a corresponding increase in SN-38 levels (128%) at a concentration of near 200 μg/mL. Tannic acid produced a 75% decrease in SN-38G with a 130% increase in SN-38 at 10 μg/mL, whereas the treatment with beta-pentagalloyl glucose and various analogues decreased SN-38G by 70% and increased SN-38 by 20% at 10 μg/mL. Conclusions These results suggest naturally occurring compounds from WWB may have the potential to increase potency by increasing the conversion of IR to SN-38 and decrease dose-limiting toxicity of IR chemotherapy by reducing glucuronidation of SN-38.","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76954374","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}
S. Imran, Mohd Khalid, Nazim Husain, Mohd. Qudratullah Khan, Shalina Shaikh
Abstract Objectives Chronic atopic dermatitis (AD) is an inflammatory skin condition marked by intense pruritus, dry skin, and severe impact on the life quality of the patients. Conventionally, it is managed by using emollients, calcineurin inhibitors, and topical corticosteroids. In Unani medicine, eminent scholars advocated many drug formulations including topical Marham-e-Akbar for effective healing of AD but scientific evidence is scarce. Hence, this study was designed. Methods This was a single-arm clinical trial conducted on 30 participants aged 18–65 years suffering from chronic AD after obtaining written informed consent. The trial intervention was Marham-e-Akbar consisting of Murdār Sang (Plumbi oxidum); Sindūr (red lead); olive oil (Olea europaea oil); Kath (Acacia catechu extract); Safeda Kāshgari (Zinc oxide); Sirka (vinegar); and Phitkirī (alum) to be applied twice daily for 42 days. The objective parameters were SCORAD and DLQI, while the subjective parameters included itching, scaling, and erythema assessed on a customized VAS scale and 4-point Likert scale. Results The pre-post analysis inferred statistically significant attenuation in subjective parameters (itching, scaling, and erythema) and objective scales (SCORAD) and (DLQI) with p<0.001. Conclusions The study findings deduced that Marham-e-Akbar is effective in the amelioration of chronic atopic dermatitis and quality of life of the patients as well.
摘要目的慢性特应性皮炎(AD)是一种以强烈瘙痒、皮肤干燥为特征的炎症性皮肤疾病，严重影响患者的生活质量。通常，它是通过使用润肤剂、钙调磷酸酶抑制剂和局部皮质类固醇来管理的。在Unani医学中，著名学者提倡许多药物配方，包括局部用药Marham-e-Akbar，以有效治疗AD，但科学证据很少。因此，设计了本研究。方法:在获得书面知情同意后，对30名年龄在18-65岁的慢性AD患者进行单臂临床试验。试验干预是Marham-e-Akbar，由Murdār Sang (Plumbi oxidum)组成;Sindūr(红铅);橄榄油(Olea europaea oil);儿茶提取物;Safeda Kāshgari(氧化锌);Sirka(醋);和phitkiri(明矾)，每天使用两次，持续42天。客观参数为SCORAD和DLQI，主观参数为瘙痒、脱屑和红斑，采用定制的VAS量表和4点Likert量表进行评估。结果经前后分析，主观指标(瘙痒、结垢、红斑)和客观指标(SCORAD)、DLQI均有统计学意义的降低(p<0.001)。结论本研究结果表明，marhamm -e- akbar能有效改善慢性特应性皮炎患者的生活质量。
{"title":"The efficacy of topical Marham-e-Akbar in chronic atopic dermatitis – an open-label interventional study","authors":"S. Imran, Mohd Khalid, Nazim Husain, Mohd. Qudratullah Khan, Shalina Shaikh","doi":"10.1515/dmpt-2021-0195","DOIUrl":"https://doi.org/10.1515/dmpt-2021-0195","url":null,"abstract":"Abstract Objectives Chronic atopic dermatitis (AD) is an inflammatory skin condition marked by intense pruritus, dry skin, and severe impact on the life quality of the patients. Conventionally, it is managed by using emollients, calcineurin inhibitors, and topical corticosteroids. In Unani medicine, eminent scholars advocated many drug formulations including topical Marham-e-Akbar for effective healing of AD but scientific evidence is scarce. Hence, this study was designed. Methods This was a single-arm clinical trial conducted on 30 participants aged 18–65 years suffering from chronic AD after obtaining written informed consent. The trial intervention was Marham-e-Akbar consisting of Murdār Sang (Plumbi oxidum); Sindūr (red lead); olive oil (Olea europaea oil); Kath (Acacia catechu extract); Safeda Kāshgari (Zinc oxide); Sirka (vinegar); and Phitkirī (alum) to be applied twice daily for 42 days. The objective parameters were SCORAD and DLQI, while the subjective parameters included itching, scaling, and erythema assessed on a customized VAS scale and 4-point Likert scale. Results The pre-post analysis inferred statistically significant attenuation in subjective parameters (itching, scaling, and erythema) and objective scales (SCORAD) and (DLQI) with p<0.001. Conclusions The study findings deduced that Marham-e-Akbar is effective in the amelioration of chronic atopic dermatitis and quality of life of the patients as well.","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80074561","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. Ishola, T. Olubodun-Obadun, Oluwasayo A. Bakre, E. Ojo, O. Adeyemi
Abstract Objectives This study sought to investigate the beneficial effect of kolaviron (KV) (a biflavonoid) isolated from Garcinia kola seed on chronic unpredictable mild stress (CUMS)-induced anxiety- and depressive-like behavior. Methods Male albino mice were randomly divided into six groups (n=8) as follows; Group I: vehicle-control unstressed; Group II: CUMS-control; Group III-V: CUMS + KV 1, 5 or 50 mg/kg, respectively, Group VI: KV (50 mg/kg, p.o.) unstressed mice. Animals were subjected to CUMS for 14 days, followed by estimation of depressive- and anxiety-like behavior from days 14–16. This was followed by biochemical assays for oxidative stress, hypothalamo-pituitary axis, cholinergic, and BDNF signaling. Results CUMS caused significant reduction in time spent in open arms of elevated plus maze test (EPM) and increase in immobility time in tail suspension test (TST) and forced swim test (FST) ameliorated by KV treatments. KV administration also attenuated CUMS-induced malondialdehyde/nitrite generation and decrease in antioxidant enzymes activities in the prefrontal cortex and hippocampus. CUMS increased serum corticosterone, acetylcholinesterase activity, and reduced BDNF level in the PFC and hippocampus were attenuated by KV administration. Conclusions KV prevented CUMS induced anxiety- and depression-like behavior in mice through enhancement of antioxidant defense mechanisms, neurotrophic factors, and cholinergic systems.
{"title":"Kolaviron ameliorates chronic unpredictable mild stress-induced anxiety and depression: involvement of the HPA axis, antioxidant defense system, cholinergic, and BDNF signaling","authors":"I. Ishola, T. Olubodun-Obadun, Oluwasayo A. Bakre, E. Ojo, O. Adeyemi","doi":"10.1515/dmpt-2021-0125","DOIUrl":"https://doi.org/10.1515/dmpt-2021-0125","url":null,"abstract":"Abstract Objectives This study sought to investigate the beneficial effect of kolaviron (KV) (a biflavonoid) isolated from Garcinia kola seed on chronic unpredictable mild stress (CUMS)-induced anxiety- and depressive-like behavior. Methods Male albino mice were randomly divided into six groups (n=8) as follows; Group I: vehicle-control unstressed; Group II: CUMS-control; Group III-V: CUMS + KV 1, 5 or 50 mg/kg, respectively, Group VI: KV (50 mg/kg, p.o.) unstressed mice. Animals were subjected to CUMS for 14 days, followed by estimation of depressive- and anxiety-like behavior from days 14–16. This was followed by biochemical assays for oxidative stress, hypothalamo-pituitary axis, cholinergic, and BDNF signaling. Results CUMS caused significant reduction in time spent in open arms of elevated plus maze test (EPM) and increase in immobility time in tail suspension test (TST) and forced swim test (FST) ameliorated by KV treatments. KV administration also attenuated CUMS-induced malondialdehyde/nitrite generation and decrease in antioxidant enzymes activities in the prefrontal cortex and hippocampus. CUMS increased serum corticosterone, acetylcholinesterase activity, and reduced BDNF level in the PFC and hippocampus were attenuated by KV administration. Conclusions KV prevented CUMS induced anxiety- and depression-like behavior in mice through enhancement of antioxidant defense mechanisms, neurotrophic factors, and cholinergic systems.","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73802798","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号