Samuel Inshutiyimana, Michael Matiop Aleu, Mustaf Aden Abdinoor, Mariyah Murtaza Janoowalla, Norhayati Norhayati
{"title":"Diloxanide in amoebiasis management: Unravelling the mechanism of action and effectiveness.","authors":"Samuel Inshutiyimana, Michael Matiop Aleu, Mustaf Aden Abdinoor, Mariyah Murtaza Janoowalla, Norhayati Norhayati","doi":"10.1111/bcpt.14106","DOIUrl":"https://doi.org/10.1111/bcpt.14106","url":null,"abstract":"<p><p>Although diloxanide is a drug of choice for treating asymptomatic amoebiasis, its mechanism of action (MOA) remains unclear. This review aims to shed light on the current understanding of the effectiveness and MOA of diloxanide in treating amoebiasis . It involves analysis of articles, retrieved from PubMed, Google Scholar and EBSCOhost, on diloxanide and the treatment of Entamoeba histolytica infection. Diloxanide is used in an ester form, which allows its high luminal concentration and greater efficacy than metronidazole in the management of asymptomatic amoebiasis. The current understanding of the action of diloxanide is based on its structural similarity to chloramphenicol at dichloroacetamide group. It acts against protein synthesis in E. histolytica trophozoites, blocking their conversion to more virulent and invasive cyst forms. Furthermore, it has a parasite clearance rate of 81-96% and treats amoebic abscesses when combined with metronidazole and chloroquine. Nevertheless, it is associated with adverse events such as flatulence, anorexia, headache and urticaria. Diloxanide is efficacious against amoebiasis but there is a need to explore its structure-activity relationship.The study suggests future directions, including novel drug formulations, diagnostic improvements, and combination regimens to enhance treatment outcomes and mitigate relapse associated with the use of diloxanide.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heresh Rezaei, Hong-Wei Wang, Weishun Tian, Jing Zhao, Asma Najibi, Socorro Retana-Márquez, Elahe Rafiei, Ayeh Rowhanirad, Samira Sabouri, Mohammadreza Kiafar, Rahil Fazlinezhad, Amir Mohammad Niknahad, Fatemeh Evazzadeh, Seyedeh Tayebeh Anousheh, Mohammad Mehdi Ommati, Hossein Niknahad, Reza Heidari
{"title":"Long-term taurine supplementation regulates brain mitochondrial dynamics in mice.","authors":"Heresh Rezaei, Hong-Wei Wang, Weishun Tian, Jing Zhao, Asma Najibi, Socorro Retana-Márquez, Elahe Rafiei, Ayeh Rowhanirad, Samira Sabouri, Mohammadreza Kiafar, Rahil Fazlinezhad, Amir Mohammad Niknahad, Fatemeh Evazzadeh, Seyedeh Tayebeh Anousheh, Mohammad Mehdi Ommati, Hossein Niknahad, Reza Heidari","doi":"10.1111/bcpt.14101","DOIUrl":"10.1111/bcpt.14101","url":null,"abstract":"<p><strong>Background: </strong>Taurine (TAU) is the most abundant non-protein amino acid in the central nervous system (CNS). However, the molecular mechanism of TAU in the CNS is still poorly understood. Meanwhile, disruption in mitochondrial dynamics is evident in CNS disorders. This study aimed to investigate the effect of TAU on mitochondrial dynamics.</p><p><strong>Methods: </strong>TAU (0.25, 0.5 and 1% in drinking water) was administered to young mice for six months. Several memory/cognition parameters and indices of anxiety/depression were assessed. Meanwhile, various mitochondrial indices and the expression/activity of genes involved in mitochondrial biogenesis and dynamics (Akt, CREB, NRF1, TFAM, PGC-1α, Mfn1, Mfn2, UCP2, PINK1, OPA1, Drp1 and Fis1) were examined.</p><p><strong>Results: </strong>TAU significantly enhanced memory performance, suppressed anxiety and depression-like behaviour, increased mitochondrial biogenesis/dynamics and improved mitochondrial indices. It should be mentioned that there was no significant difference between different concentrations of TAU in changing most brain mitochondrial dynamic biomarkers in the current study.</p><p><strong>Conclusions: </strong>These findings offer more insights into the molecular mechanism for TAU's action in the CNS. However, there is a need for further research to confirm these effects in humans. Overall, this study suggests the potential application of TAU in various neurological disorders and the need for clinical studies on the effects of this amino acid in the brain.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Syringin ameliorates dextran sulphate colitis via alteration oxidative stress, inflammation NF-κB signalling pathway and gut microbiota.","authors":"Juhui Zhao, Qingqing Zhang, Xudong Hao","doi":"10.1111/bcpt.14105","DOIUrl":"https://doi.org/10.1111/bcpt.14105","url":null,"abstract":"<p><strong>Background: </strong>The objective of the current study was to investigate the potential effects of syringin against dextran sulphate colitis (DSS)-induced ulcerative colitis (UC) in mice.</p><p><strong>Material and methods: </strong>In vitro study was performed on the RAW 264.7 cells and cytokines and inflammatory level were estimated. The oxidative stress, inflammatory cytokines, apoptosis and inflammatory parameters were estimated. The mRNA expression and faecal samples were estimated in the colon tissue.</p><p><strong>Results: </strong>Syringin treatment enhanced the body weight, colon length and reduced the disease activity index (DAI), spleen index. Syringin treatment remarkably suppressed the level of nitric oxide (NO), myeloperoxidase (MPO), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) along with alteration of antioxidant parameters. Syringin treatment also altered level of cytokines in the serum and colon tissue; inflammatory parameters viz., platelet-activating factor (PAF), cyclooxygenase-2 (COX-2), prostaglandin (PGE<sub>2</sub>), inducible nitric oxide synthetase (iNOS), nuclear factor κ-B (NF-κB); matrix metalloproteinases (MMP) level. Syringin significantly (p < 0.001) enhanced the level of nuclear factor erythroid 2-related factor (Nrf<sub>2</sub>) and heme oxygenase-1 (HO-1). Syringin remarkably altered the relative abundance of gut microbiota like Firmicutes, Bacteroidetes, F/B ratio, Verrucomicrobia and Actinobacteria.</p><p><strong>Conclusion: </strong>Syringin exhibited the protective effect against DSS-induced UC in mice via alteration of NF-κB signalling pathway.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mella Louhisalmi, Piia Lavikainen, Kari Linden, Janne Martikainen, Johanna Timonen
{"title":"Amount, type and storage of medicines in households - A survey for medicine users.","authors":"Mella Louhisalmi, Piia Lavikainen, Kari Linden, Janne Martikainen, Johanna Timonen","doi":"10.1111/bcpt.14104","DOIUrl":"10.1111/bcpt.14104","url":null,"abstract":"<p><p>With increasing medicine use, more medicines are being stored at home, yet the understanding of household medicines remains limited. This study aimed to assess the amount, type and storage practices of medicines in households. It also explored the reasons for unnecessary or expired medicines, as well as the factors associated with the presence of expired medicines in a household. The online survey was conducted among loyal customers of University Pharmacy in June 2023 (n = 5004). The data were analysed for frequencies and percentages, and binary logistic regression was used to examine the association between background factors and expired medicines in households. On average, one household had 13.9 active, 2.8 unnecessary and 2.2 expired medicine packs. Medicines were typically stored in the kitchen (67.0%) and in cabinets (58.7%), and 40% were to be stored safely. The main reasons for unnecessary or expired medicines were improved health (39.2%), medication changes (31.9%) and oversized packs (28.0%). Households returning medicines biennially (odds ratio (OR): 2.85; 95% confidence interval (CI): 2.13-3.82) and those with many active medicines (OR: 2.14; 95% CI: 1.79-2.54) had expired medicines more often. The study showed that households had many medicines, highlighting the need for better storage and optimized packaging to improve safety, reduce waste and enhance rational pharmacotherapy.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xin Chen, Denis Delić, Yvonne Liu, Yaochen Cao, Zeyu Zhang, Hongwei Wu, Mohamed M S Gaballa, Thomas Klein, Saban Elitok, Bernhard K Krämer, Berthold Hocher
{"title":"sGC stimulator (BAY 41-8543) combined with PDE9 inhibitor (BAY 73-6691) reduces renal fibrosis in 5/6 nephrectomized rats.","authors":"Xin Chen, Denis Delić, Yvonne Liu, Yaochen Cao, Zeyu Zhang, Hongwei Wu, Mohamed M S Gaballa, Thomas Klein, Saban Elitok, Bernhard K Krämer, Berthold Hocher","doi":"10.1111/bcpt.14103","DOIUrl":"https://doi.org/10.1111/bcpt.14103","url":null,"abstract":"<p><p>Renal fibrosis is closely related to the prognosis of chronic kidney disease (CKD). The increase in cGMP reduces renal fibrosis. Soluble guanylate cyclase (sGC) and phosphodiesterase (PDE) are key enzymes that maintain cGMP levels. BAY 41-8543 (1 mg/kg/day) and/or BAY 73-6691 (1 mg/kg/day) were used to treat 5/6 nephrectomized rats for 13 weeks. 5/6 Nephrectomy caused an increase in cystatin C, proteinuria and glomerulosclerosis and renal interstitial fibrosis. Neither sGC stimulation nor PDE9 inhibition alone improved kidney function and morphology, whereas BAY 41-8543 in combination with BAY 73-6691 attenuated renal interstitial fibrosis. This beneficial effect could not be explained by alterations in blood pressure and the renal immune system. BAY 41-8543 in combination with BAY 73-6691 had no effect on renal macrophage, CD4 + T-cell and CD8 + T-cell in the late-stage of 5/6 nephrectomy. RNA sequencing revealed BAY 41-8543 in combination with BAY 73-6691 down-regulated the expression of fibrosis-related genes such as Collagen Type I Alpha 1, Collagen Type III Alpha 1 Chain and Collagen Type XIV Alpha 1 Chain. sGC stimulator combined with PDE9 inhibitor attenuated renal fibrosis in 5/6 nephrectomized rats by down-regulating fibrosis-related gene expression. This novel approach of using low-dose combination therapies to minimize side effects while maintaining therapeutic efficacy offers a promising strategy for the treatment of CKD.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dichloroacetate, a pyruvate dehydrogenase activator, alleviates high-fat-induced impairment of myogenic differentiation in skeletal muscles.","authors":"Chuang-Yen Huang, I-Shan Han, Po-Shiuan Hsieh, Min-Chien Tsai, Hung-Che Chien","doi":"10.1111/bcpt.14102","DOIUrl":"https://doi.org/10.1111/bcpt.14102","url":null,"abstract":"<p><p>Obesity-induced impairment of myogenic differentiation leads to muscle loss and sarcopenia. Pyruvate dehydrogenase (PDH) plays a crucial role in glucose metabolism and is associated with muscle differentiation. However, the effect of dichloroacetate (DCA), a PDH activator, on obesity-induced impairment of myogenic differentiation remains unknown. Here, we evaluated the effects of DCA treatment on high-fat intake-induced impairment of myogenic differentiation in C2C12 cells and C57BL/6 mice. In C2C12 cells, DCA treatment improved PDH activity that was reduced by palmitate (PAL) and decreased the lactate concentrations in the media. Additionally, DCA reversed PAL- and high-fat diet (HFD)-induced decrease in the expression of myoblast determination protein 1 (MyoD), myogenin (MyoG) and myosin heavy chain (MyHC) in C2C12 cells and C57BL/6 mice. To explore the possible mechanism, DCA treatment restored the levels of p-Akt, p-FoxO1, p-FoxO3a and p-p38 MAPK levels in PAL-treated C2C12 cells. Moreover, the protective effects of DCA were reversed by treatment with the Akt inhibitor MK2206 in C2C12 cells. In summary, DCA treatment alleviated high-fat intake-induced impairment of myogenic differentiation via Akt signalling, suggesting its potential in treating obesity-associated muscle loss and sarcopenia.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elin Lindqvist, Jacob Hollenberg, Mattias Ringh, Per Nordberg, Henrik Druid, Leif Svensson, Sune Forsberg
{"title":"A nationwide Swedish retrospective study on poisoning deaths between the years 2000 and 2022.","authors":"Elin Lindqvist, Jacob Hollenberg, Mattias Ringh, Per Nordberg, Henrik Druid, Leif Svensson, Sune Forsberg","doi":"10.1111/bcpt.14097","DOIUrl":"https://doi.org/10.1111/bcpt.14097","url":null,"abstract":"<p><strong>Background: </strong>Approximately 1% of Sweden's 90 000 annual deaths were reported caused by poisoning. In this study, we aim to describe this poisoning population's characteristics, autopsy frequency and results of toxicology testing.</p><p><strong>Method: </strong>A national cohort study based on Swedish national registers. All deceased subjects older than 18 years with poisoning as the cause of death registered between 1 January 2000 and 31 December 2021 were included. Causes of death according to primary ICD-10 code were analysed along with the substances found in forensic chemistry testing.</p><p><strong>Results: </strong>There were 27 057 poisonous deaths during the study periods 2 018 495 adult deaths. Subjects deceased due to poisoning had a median age of 53 years, and 18 838 (70%) were men. A private home was the most reported location of death (52%). In total, 23 260 (87%) did undergo some sort post-mortem examination. Drugs (synthetic narcotics, opioids, heroin) caused 12 448 (46%) deaths, and alcohols explained 9056 cases (33%). Positive toxicological tests were found in 22 550 (83%) of the subjects. The most common separate substances were ethanol, zopiclone and nordazepam.</p><p><strong>Conclusion: </strong>Poisoning caused 1.3% of Swedish deaths. Men in their 50s were the most common victims, and their deaths were often cause by synthetic narcotics, other opioids or alcohol. The autopsy frequency was lower than expected for poisonous deaths.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erik Melander, Elisabet I Nielsen, Annika Lindqvist, Markus Hovd, Peggy Gandia, Alice Panchaud, Monia Guidi, Pieter Annaert, Pawel Baranczewski, Olav Spigset, Hedvig Nordeng
{"title":"Population pharmacokinetic modelling of cetirizine concentrations in human breast milk-A contribution from the ConcePTION project.","authors":"Erik Melander, Elisabet I Nielsen, Annika Lindqvist, Markus Hovd, Peggy Gandia, Alice Panchaud, Monia Guidi, Pieter Annaert, Pawel Baranczewski, Olav Spigset, Hedvig Nordeng","doi":"10.1111/bcpt.14100","DOIUrl":"https://doi.org/10.1111/bcpt.14100","url":null,"abstract":"<p><p>Cetirizine is an antihistamine commonly used to treat allergic rhinitis and other allergic conditions. Cetirizine is often prescribed to breastfeeding mothers although there is limited information on infant exposure via breast milk. The aim of this study was to develop a popPK model based on data from a lactation study to predict cetirizine breast milk concentrations and estimate the relative infant dose (RID) in a breastfed infant. A popPK model was developed in NONMEM on data from a human lactation study including 35 women using cetirizine or levocetirizine while breastfeeding. Serial samples of breast milk were collected (n = 205) and the cetirizine concentrations quantified using a validated LC-MS/MS method. A one-compartment model of cetirizine in breast milk was developed and employed to calculate the relative infant dose (RID). Covariates related to the maternal characteristics and breastfeeding patterns were evaluated in the model; only milk sampling pumping duration was found to be a significant covariate, with an increasing pumping duration leading to an increased apparent milk volume of distribution (V<sub>m</sub>). The mean RID was 1.99% with the highest RID being 3.36% at C<sub>max</sub>. PopPK modelling could be used to estimate infant exposure to cetirizine via breast milk. The low predicted exposure in infants supports that cetirizine is compatible with breastfeeding.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hege-Merete Krabseth, Magnus Strømmen, Arne Helland, Olav Spigset
{"title":"Effect of bariatric surgery on the pharmacokinetics of drugs used for attention-deficit hyperactivity disorder-A case series.","authors":"Hege-Merete Krabseth, Magnus Strømmen, Arne Helland, Olav Spigset","doi":"10.1111/bcpt.14099","DOIUrl":"https://doi.org/10.1111/bcpt.14099","url":null,"abstract":"<p><strong>Background: </strong>Changes in gastrointestinal physiology following bariatric surgery may affect the pharmacokinetics of drugs. Data on the impact of bariatric surgery on drugs used for attention-deficit/hyperactivity disorder (ADHD) are limited.</p><p><strong>Methods: </strong>In patients treated with ADHD medication and undergoing bariatric surgery, serial drug concentrations were measured for 24 h preoperatively and one, six and 12 months postoperatively. Primary outcome was change in area under the concentration-time curve from 0 to 24 h (AUC<sub>0-24</sub>), with other pharmacokinetic variables as secondary outcomes.</p><p><strong>Results: </strong>Eight patients treated with lisdexamphetamine (n = 4), dexamphetamine (n = 1), methylphenidate (n = 1) and atomoxetine (n = 2) were included. In total, 409 samples were analysed. Patients underwent sleeve gastrectomy (n = 5) and Roux-en-Y gastric bypass (n = 3). AUC<sub>0-24</sub> and C<sub>max</sub> of dexamphetamine increased after surgery in those using the prodrug lisdexamphetamine. There was no clear-cut reduction in t<sub>max</sub> postoperatively. For ritalinic acid and atomoxetine, no changes in AUC<sub>0-24</sub> were observed, but for atomoxetine, a higher C<sub>max</sub> and a shorter t<sub>max</sub> were observed postoperatively.</p><p><strong>Conclusion: </strong>Bariatric surgery may increase the systemic exposure of dexamphetamine after intake of lisdexamphetamine. Patients using lisdexamphetamine should be followed with regard to adverse drug reactions after bariatric surgery, and, if available, therapeutic drug monitoring should be considered.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}