Fundamental & Clinical Pharmacology最新文献

{"title":"Impacts of genetic polymorphisms and cancer cachexia on naldemedine pharmacokinetics and bowel movements in patients receiving opioid analgesics","authors":"Emi Nakatsugawa,&nbsp;Takafumi Naito,&nbsp;Kaito Shibata,&nbsp;Ryo Kitajima,&nbsp;Junichi Kawakami","doi":"10.1111/fcp.12976","DOIUrl":"10.1111/fcp.12976","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Objectives</h3>\u0000 \u0000 <p>Clinical responses to naldemedine vary between individuals with advanced cancer. This is a prospective, single-center, observational study aimed to evaluate the influence of genetic polymorphisms and cachexia status on plasma naldemedine and clinical responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty-eight patients being treated with naldemedine for opioid-induced constipation under treatment of cancer pain were enrolled. Plasma naldemedine concentrations were determined on the fourth day or later after administration of naldemedine, and the associations with genotypes, cachexia status, and clinical responses were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cancer patients exhibited a large variation in the plasma naldemedine concentrations, and it was correlated with serum total protein level. Patients who were homozygous <i>CYP3A5*3</i> had a higher plasma concentration of naldemedine than those with the <i>*1</i> allele. ABCB1 genotypes tested in this study were not associated with plasma naldemedine. A negative correlation was observed between the plasma naldemedine concentration and 4β-hydroxycholesterol level. The plasma naldemedine concentration was lower in patients with refractory cachexia than in those with precachexia and cachexia. While serum levels of interleukin-6 (IL-6) and acute-phase proteins were higher in patients with refractory cachexia, they were not associated with plasma naldemedine. A higher plasma concentration of naldemedine, <i>CYP3A5*3/*3</i>, and an earlier naldemedine administration after starting opioid analgesics were related to improvement of bowel movements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Plasma naldemedine increased under deficient activity of CYP3A5 in cancer patients. Cachectic patients with a higher serum IL-6 had a lower plasma naldemedine. Plasma naldemedine, related to CYP3A5 genotype, and the initiation timing of naldemedine were associated with improved bowel movements.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.12976","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The comparison of the antidiabetic effects of exenatide, empagliflozin, quercetin, and combination of the drugs in type 2 diabetic rats","authors":"Yasemin Korkmaz,&nbsp;Burak Dik","doi":"10.1111/fcp.12975","DOIUrl":"10.1111/fcp.12975","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Type 2 diabetes, a metabolic disease that involves extended treatment, is rapidly increasing in humans and animals worldwide.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to compare monotherapy and combined therapy of exenatide, empagliflozin, and quercetin in 67 Wistar Albino male rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The animals were divided into the following seven groups: healthy control, diabetes control, diabetes + sham, diabetes + exenatide (10 μg/kg), diabetes + empagliflozin (50 mg/kg), diabetes + quercetin (50 mg/kg), and diabetes + combination treatment. The treatments were continued for 8 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At the end of the experiment, glucose and HbA1c levels decreased with all monotherapy treatments and the combination treatments, while insulin levels increased with exenatide and combined treatments. Adiponectin levels increased with empagliflozin, quercetin, and combined treatments, while leptin levels decreased only with combined treatments. All monotherapies caused an increase in total antioxidant levels. Exenatide and quercetin treatments reduced low-density lipoprotein (LDL) levels; therewithal, exenatide and combined treatments increased high-density lipoprotein (HDL) levels. Triglyceride levels decreased in all treatment groups. The homeostatic model assessment for insulin resistance (HOMA-IR) level decreased with the combined treatment; on the contrary, the homeostatic model assessment for β-cell activity (HOMA-β) level increased with empagliflozin, exenatide, and combined treatments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, the antidiabetic effects of exenatide were more pronounced than empagliflozin and quercetin, however, the combined treatment had better antidiabetic and antihyperlipidemic effects than monotherapies. Quercetin could be a supportive or food supplement antidiabetic agent. The exenatide treatment can be recommended for monotherapy in type 2 patients, and the combination of empagliflozin, exenatide, and quercetin may be effective in diabetic patients who need combined therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039736","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":"Antimalarial activities of benzothiazole analogs: A systematic review","authors":"Linh Tran,&nbsp;Vo Linh Tu,&nbsp;Mohammad Najm Dadam,&nbsp;Jeza Muhamad Abdul Aziz,&nbsp;Tran Le Dinh Duy,&nbsp;Hajer Hatim Hassan Ahmed,&nbsp;Patrick Amanning Kwaah,&nbsp;Hoang Nghia Quoc,&nbsp;Truong Van Dat,&nbsp;Satoshi Mizuta,&nbsp;Kenji Hirayama,&nbsp;Nguyen Tien Huy","doi":"10.1111/fcp.12974","DOIUrl":"10.1111/fcp.12974","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Benzothiazole derivatives have been reported to possess a wide range of biological activities, including antimalarial activity. This systematic review aims to summarize and evaluate the antimalarial activities of benzothiazole analogs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted an electronic search using nine databases in October 2017 and subsequently updated in September 2022. We included all original in vitro and in vivo studies that documented the antimalarial activities of compounds containing benzothiazole analogs with no restriction. The risk of bias of each included study was assessed by ToxRTool.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-eight articles were included in our study, which are in vitro, in vivo, or both. Of these, 232 substances were identified to have potent antiplasmodial activity against various strains of the malaria parasite. Benzothiazole analogs show different antimalarial mechanisms, including inhibition of <i>Plasmodium falciparum</i> enzymes in in vitro studies and inhibition of blood parasites in in vivo studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Benzothiazole derivatives are promising substances for treating malaria. The structure–activity relationship studies suggest that the substitution pattern of the benzothiazole scaffold plays a crucial role in determining the antimalarial activity of the analog.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037578","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":"Lacosamide use during breastfeeding: A case report and a literature review","authors":"Morgan Cercos,&nbsp;Ines Seqat,&nbsp;Anthony Facile,&nbsp;Thierry Vial,&nbsp;Marine Auffret","doi":"10.1111/fcp.12971","DOIUrl":"10.1111/fcp.12971","url":null,"abstract":"<p>Lacosamide, a voltage-gated sodium channel inhibitor, is an anti-seizure medication (ASM) from the age of 4. We report on the case of a woman treated with lacosamide for pharmacoresistant epilepsy who breastfed her infant for more than 6 months after birth. The infant's blood concentrations of lacosamide were 2.4 mg/L on Day 1 and less than 1 mg/L on Day 10 (reference values are 1–10 mg/L). No adverse drug reactions (ADRs) were reported for the infant. Eight cases of breastfeeding by mothers receiving lacosamide are described in the literature. These data confirm that a significant amount of lacosamide seems to pass into breast milk, with a relative infant dose (RID) above 20% in two cases but a low RID (1.8%) in another case. Nevertheless, blood tests, performed in two breastfed infants, revealed low concentrations of lacosamide. No ADRs were reported in eight of the breastfed infants; however, one infant, whose mother was also treated with levetiracetam, presented poor feeding and sleepiness at Day 15 of life. Given the well-known benefits of breastfeeding for both mothers and their infants, as well as the above reassuring data, breastfeeding of healthy full-term infants could be possible for mothers on lacosamide monotherapy. Nonetheless, relatives should be warned that data concerning the safety of lacosamide during breastfeeding are scarce and that long-term neurodevelopment outcomes in breastfed children are unknown. Clinical monitoring of breastfed infants for drowsiness, adequate weight gain, or cutaneous rash is recommended. Additionally, the infants' serum levels should be measured in case of an unexplained adverse reaction.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487292","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":"Effect of Bacille-Calmette-Guerin vaccine against rotenone-induced Parkinson's disease: Role of neuroinflammation and neurotransmitters","authors":"Narhari Gangaram Yedke,&nbsp;Divya Soni,&nbsp;Puneet Kumar","doi":"10.1111/fcp.12968","DOIUrl":"10.1111/fcp.12968","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD) is an extrapyramidal movement disorder associated with a hypokinetic condition generated by impairment in dopaminergic neuronal viability in the nigrostriatal region of the brain. Current medications can only provide symptomatic management; to date, no permanent cure is available. To compensate for this lacuna, researchers are gaining interest in antigen-based therapy, and Bacille-Calmette-Guerin (BCG) is one of the vaccines with a high safety margin that acts by stimulating immunoreactive T-cells in the CNS and reducing expression of pro-inflammatory cytokines including interleukin (IL)-1β and tumor necrotic factor (TNF-α) to produce neuroprotection. A previous study reported that BCG exerts a neuroprotective effect against several neurodegenerative disorders, such as Alzheimer's disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study is to explore the neuroprotective effect of the BCG vaccine against the rotenone model of PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rotenone (1.5 mg/kg, <i>s.c</i>) for 28 days, and BCG vaccine (2 × 10⁷ cfu, <i>i.p</i>) single dose was injected to rats, and behavioral assessments were performed on the 21st and 28th day. On the 29th day, rats were sacrificed, and brains were isolated for biochemical and neurochemical estimation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BCG vaccine significantly restored rotenone-induced motor deficits (open field test, narrow beam walk, and rotarod), biochemical levels (GSH, SOD, catalase, MDA, and nitrite), neurotransmitters (dopamine, 5-hydroxy tryptamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, hemovanillic acid, and 5-hydroxy indoleacetic acid), and levels of inflammatory cytokines (IL-1β and TNF-α) in the striatum. It also prevents histopathological changes by reducing eosinophilic lesions in the striatum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>From the results, we conclude that BCG vaccine showed neuroprotection through antioxidant and anti-inflammatory effect. Thus, in the future, it can be used as a neuroprotective agent for other neurological disorders, including PD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138470187","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":"Prospective pilot study evaluating a vitamin D3 loading dose in critically ill children with vitamin D deficiency","authors":"Elizabeth W. Covington,&nbsp;Shaneese L. Jasper-Trotter,&nbsp;Robert D. Arnold,&nbsp;Raj Amin,&nbsp;Susan Egbert,&nbsp;Allison Chung","doi":"10.1111/fcp.12973","DOIUrl":"10.1111/fcp.12973","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Vitamin D deficiency is a common finding in critically ill children. However, the optimal supplementation strategy in this patient population is unknown. The objective of this study was to evaluate the effects of high-dose (10 000 IU/kg, max. 400 000 IU) vitamin D supplementation on 25-hydroxyvitamin D3 (25[OH]D3) levels in pediatric intensive care unit (PICU) patients with baseline vitamin D deficiency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a prospective, institutional review board-approved pilot research study performed at the University of South Alabama Women's and Children's Hospital in Mobile, AL. The study sample consisted of patients less than 18 years old admitted to the PICU with baseline 25-hydroxyvitamin D (25[OH]D) level less than 30 ng/ml. Included patients received a one-time dose of vitamin D3 orally or via gastric tube (10 000 IU/kg, max. 400 000 IU).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 17 patients were screened with 11 included in the study. Blood analysis revealed a significant increase in 25(OH)D3 level from baseline to 12-h post dose (21.6 [4.5] ng/ml vs. 46.7 [15.5] ng/ml, <i>P</i> &lt; 0.001). At the 12-h post-dose time point, 10/11 patients (91%) had 25(OH)D3 levels that were greater than 30 ng/ml. No adverse effects were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Vitamin D3 supplementation at a dose of 10 000 IU/kg (max. 400 000 IU) significantly increased 25(OH)D3 levels in critically ill pediatric patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444459","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":"Association between immune-related adverse events and prognosis in patients treated with immune checkpoint inhibitors in melanoma: A surrogacy analysis","authors":"Romain Euvrard,&nbsp;Marie Robert,&nbsp;Sabine Mainbourg,&nbsp;Stéphane Dalle,&nbsp;Jean-Christophe Lega","doi":"10.1111/fcp.12966","DOIUrl":"10.1111/fcp.12966","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Immune checkpoint inhibitors (ICI) represent a breakthrough in oncology in terms of prognosis and safety. They now constitute a cornerstone in the management of metastatic melanoma. However, a new kind of adverse event called immune-related adverse events (irAE) has emerged. These irAE could be conceptually considered as an indicator of the antitumoral immune response, but the association between irAE and prognosis is still a matter of debate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The purpose of this study was to investigate the association between the overall survival (OS) and the prevalence of irAE in melanoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MEDLINE/PubMed, WebofScience, ClinicalTrials, and WHOTrials databases were searched to identify phase 3 randomized controlled trials (RCT) assessing ICI in melanoma and published up to April 2021. A weighted regression was performed to estimate this association according to standard method of surrogacy analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 14 RCT including 7646 patients (median age: 59.3 years) with melanoma were included. All types of ICI were represented (ipilimumab, tremelimumab, pembrolizumab, nivolumab, atezolizumab, as well as ipilimumab and nivolumab combination). irAE were frequent but rarely fatal. The combination of ICI caused more irAE than anti-PD1 (or PDL1) and anti-CTLA4 monotherapies. No relationship was found between the occurrence of irAE and OS (beta coefficient 0.078, R² 3%, <i>p</i> = 0.52), nor between cutaneous irAE and OS (beta coefficient 0.080, R² 6%, <i>p</i> = 0.33).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although limited by the heterogeneity of ICI included in the regression and the low number of included RCT, the present study suggests an absence of association between irAE and prognosis in melanoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.12966","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chlorogenic acid co-administration alleviates cisplatin-induced peripheral neuropathy in rats","authors":"Çiğdem Çengelli Ünel,&nbsp;Ezgi Eroğlu,&nbsp;Orhan Özatik,&nbsp;Kevser Erol","doi":"10.1111/fcp.12970","DOIUrl":"10.1111/fcp.12970","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chemotherapy-induced peripheral neuropathy (CIPN) is still an unresolved problem in cisplatin (CIS) use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study investigates possible anti-neuropathic effect of chlorogenic acid (CGA) against CIS-induced CIPN in rats while also investigating the contribution of nitric oxide (NO) to this phenomenon.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Initially, CGA (250–1000 μM) was tested by MTT assay on primary DRG neurons. Subsequently, CIPN was induced in Sprague–Dawley rats by 3 mg/kg intraperitoneal injections of CIS once/week for 5 weeks. CGA (100 mg/kg) was co-administered with CIS, both alone and in combination with <span>l</span>-arginine (LARG) or <span>l</span>-nitro-arginine-methyl-ester (LNAME), to elucidate the contribution of nitrergic system to anti-neuropathic effects. Mechanical allodynia, thermal hyperalgesia, and cold plate tests were performed to test CIPN. Rotarod, footprint analysis, and activitymeter were used to evaluate motor coordination and performance. Tumor necrosis factor alpha (TNF-α) was measured as a marker of inflammation. Histological evaluations of DRG and sciatic nerves (SNs) were performed utilizing toluidine blue staining. Two-way analysis of variance and Kruskal–Wallis following Tukey's test were used as statistical analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher concentration of CGA (1000 μM) exhibited protective effect against in vitro neurotoxicity. Neither LARG nor LNAME exerted significant change in this effect. Co-administration of CGA alleviated histological abnormalities and neuropathic effects induced by CIS. Ameliorative effect of CGA was not changed in mechanical allodynia but attenuated in cold allodynia, and motor activity/coordination tests by LARG and LNAME. Neuropathic effects of CIS remained unchanged with LARG and LNAME in behavioral experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study identified CGA as candidate agent in mitigating CIPN. NO seems to play a modulatory role in this effect.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298877","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":"Myrtenal exhibits cardioprotective effects by attenuating the pathological progression associated with myocardial infarction","authors":"N Abhirami,&nbsp;Mahesh Chandran,&nbsp;Athira Ramadasan,&nbsp;Dhanalekshmi Bhasura,&nbsp;Janeesh Plakkal Ayyappan","doi":"10.1111/fcp.12965","DOIUrl":"10.1111/fcp.12965","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Myocardial infarction poses major risks to human health because of their incredibly high rates of morbidity and mortality. Infarctions are more likely to develop as a result of dysregulation of cell death. Myrtenal can be considered for their bioactive beneficial activity in the context of cardiovascular pathologies and, particularly, in the protection toward oxidative stress followed by ischemic injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to put limelight on the antioxidant, anti-apoptotic, and antibacterial properties of Myrtenal.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An in vitro model of oxidative stress-induced injury was entrenched in H9c2 cells using hydrogen peroxide, and the effects of Myrtenal were investigated. The MTT, cellular enzyme level, staining, and flow cytometry analysis were used to examine protective, antioxidant, and anti-apoptotic effects. The gene expressions were detected by qPCR. Antibacterial effect and biofilm formation were also done.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>The findings revealed that Myrtenal alone had negligible cytotoxic effects and that Myrtenal protects H9c2 against H₂O₂-induced cell death at micromolar concentrations. Myrtenal pre-treatment inhibited the generation of reactive oxygen species (ROS) as well as remarkably decreased the fluorescence intensity of ROS. Additionally, Myrtenal considerably increased the synthesis of antioxidant enzymes while dramatically decreasing the production of MDA and LDH. qPCR demonstrated the downregulation of Cas-9, TNF-α, NF-κB, P53, BAX, iNOS, and IL-6 expression while an upregulation of Bcl-2 expression in Myrtenal pre-treated groups. Myrtenal also holds the magnificent property of inhibiting bacterial growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Myrtenal ameliorates H₂O₂-induced cardiomyocyte injury and protects cardiomyocyte by inhibiting oxidative stress, inflammation, and apoptosis and may be a promise drug for the treatment of heart diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290719","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":"In vitro stability study of 10 beta-lactam antibiotics in human plasma samples","authors":"Matthieu Brenkman,&nbsp;Tom Cartau,&nbsp;Elise Pape,&nbsp;Allan Kolodziej,&nbsp;Alexandre Charmillon,&nbsp;Emmanuel Novy,&nbsp;Jean-Yves Jouzeau,&nbsp;Nicolas Gambier,&nbsp;Julien Scala-Bertola","doi":"10.1111/fcp.12969","DOIUrl":"10.1111/fcp.12969","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Beta-lactam antibiotics are reported for some of them to be subject to a rapid degradation in infusion solutions and in human blood samples. However, the current data of stability available in blood samples are limited to a few number of beta-lactam antibiotics, and the methodology of the corresponding studies may be discussed. The objective of the present study is to evaluate the stability of 10 beta-lactam antibiotics in human plasma samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Stability of amoxicillin, cefazolin, cefepime, cefotaxime, cefoxitin, ceftazidime, ceftriaxone, imipenem, meropenem, and piperacillin was evaluated at low and high concentrations at 20°C, 4°C, −20°C, and −80°C for 1, 7, 60, and 90 days, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Amoxicillin, cefepime, meropenem, and piperacillin were the least stable antibiotics. The maximum durations allowing the stability for all the evaluated beta-lactams at both tested concentrations were estimated at 3 h, 23 h, 10 days, and 35 days at 20°C, 4°C, −20°C, and −80°C, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We recommend to transport antibiotic plasma samples in ice at 4°C and even at −20°C if these samples come from external hospitals. Ideally, plasma samples should be stored at −80°C if possible; if not, the analysis of the samples should be performed as soon as possible in the limit of 10 days after a storage at −20°C.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138176060","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}