Fundamental & Clinical Pharmacology最新文献

{"title":"Repurposing of atorvastatin and metformin denotes their individual and combined antiproliferative effects in non-small cell lung cancer","authors":"Elsayed I. Salim,&nbsp;Safaa Elsebakhy,&nbsp;Mohamed Hessien","doi":"10.1111/fcp.12981","DOIUrl":"10.1111/fcp.12981","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Due to the limited success in the treatment of lung adenocarcinomas, new treatment protocols are urgently needed to increase the curability rate and the survival of lung cancer patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Although statins, like atorvastatin (Ator), and metformin (Met) are widely accepted as hypolipidemic and hypoglycemic drugs, respectively, there are many predictions about their enhancing antitumor effect when they are combined with traditional chemotherapeutics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The individual and combined antiproliferative potential of Ator and Met was tested by MTT-assay in non-small cell lung cancer (NSCLC) A549 cell line, compared to the corresponding effect of Gemcitabine (Gem) with implication on the mechanisms of action.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Initially, both drugs demonstrated concentration-dependent cytotoxicity in A549 cells. Also, their combination index (CI) indicated their synergistic effect at equi-IC50 concentration (CI = 0.00984). Moreover, Ator and/or Met-treated cells revealed disrupted patterns of SOD, CAT, GSH, MDA, and TAC, developed apoptosis, and larger fractions of the cell population were arrested in G0/G1 phase, particularly in cells dually-treated both Ator and Met. These observations were accompanied by downregulation in the expression of <i>iNOS</i>, <i>HO-1</i>, and the angiogenic marker <i>VEGF</i>, meanwhile, an altered expression of <i>MAPK</i> and <i>AMPK</i> was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Conclusively, these data suggest that repurposing of Ator and Met demonstrates their individual and combined antiproliferative effect in non-small cell lung cancer and they may adopt a similar mechanism of action.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 3","pages":"550-560"},"PeriodicalIF":2.9,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520490","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":"Probing polypharmacy, ageing and sex effects on physical function using different tests","authors":"Gizem Gemikonakli,&nbsp;John Mach,&nbsp;Trang Tran,&nbsp;Harry Wu,&nbsp;Sarah N. Hilmer","doi":"10.1111/fcp.12978","DOIUrl":"10.1111/fcp.12978","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ageing, sex and polypharmacy affect physical function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This mouse study investigates how ageing, sex and polypharmacy interact and affect grip strength, balance beam and wire hang, correlating and comparing the different test results between and within subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Young (2.5 months) and old (21.5 months) C57BL/6 J male and female mice (<i>n =</i> 10–6/group) were assessed for physical function at baseline on grip strength, balance beam and wire hang with three trials of 60 s (WH60s) and one trial of 300 s (WH300s). Mice were randomised to control or diet containing a high Drug Burden Index (DBI, total anticholinergic and sedative drug exposure) polypharmacy regimen (metoprolol, simvastatin, citalopram, oxycodone and oxybutynin at therapeutic oral doses). Following 6–8 weeks of treatment, mice were reassessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High DBI polypharmacy and control mice both showed age group differences on all tests (<i>p &lt;</i> 0.05). Only control mice showed sex differences, with females outperforming males on the WH60s and balance beam for old mice, WH300s for young mice (<i>p &lt;</i> 0.05). Polypharmacy reduced grip strength in all subgroups (<i>p &lt;</i> 0.05) and only in old females reduced wire hang time and cumulative behaviour and balance beam time and %walked (<i>p &lt;</i> 0.05). Physical function assessments were all correlated with each other, with differences between subgroups (<i>p &lt;</i> 0.05), and mice within subgroups showed interindividual variability in performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Age, sex and polypharmacy have variable effects on different tests, and behavioural measures are useful adjuvants to assessing performance. There was considerable within-group variability in change in measures over time. These findings can inform design and sample size of future studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 3","pages":"561-574"},"PeriodicalIF":2.9,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.12978","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511224","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":"Update on monkeypox virus infection: Focusing current treatment and prevention approaches","authors":"Rishika Dhapola,&nbsp;Sneha Kumari,&nbsp;Prajjwal Sharma,&nbsp;Pramod KumarKushawaha,&nbsp;Dibbanti HariKrishnaReddy","doi":"10.1111/fcp.12980","DOIUrl":"10.1111/fcp.12980","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>While the world is still facing the global pandemic COVID-19, another zoonosis monkeypox (Mpox) has emerged posing a great threat to society. Insight into the pathogenesis, symptoms, and management strategies will aid in the development of potent therapeutics for the treatment of monkeypox virus infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To get insight into the current treatment and prevention strategies will aid in effectively coping with the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For obtaining information regarding the ongoing treatment and prevention strategies and the drugs under pipeline, we referred to Google Scholar, Pub Med, Pub Chem, and WHO official site.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There are a few drugs that came out to be effective for the treatment of Mpox. Tecovirimat acts by inhibiting viral replication and viral wrapping. Another drug is cidofovir, which hinders the activity of viral DNA polymerase but has the drawback of nephrotoxicity. To overcome this, a conjugate of cidofovir is being used—known as brincidofovir—which has a similar mechanism as cidofovir but lesser toxicity. Ribavirin acts via inhibiting inosine monophosphate dehydrogenase (IMPDPH) thus disrupting viral translation. It also interferes with helicase activity. Tiazofurin, Adenosine N1 oxide, and HPMPA have shown efficacy in in-vitro studies by inhibiting IMPDH, DNA polymerase, and viral mRNA translation respectively. <i>In-silico</i> studies have proven the effect of nilotinib, simeprevir, and dihydroergotamine for Mpox treatment. They have shown binding affinity for proteins required for the growth and release of MPXV. Vaccines have also been employed for the prevention of Mpox, which includes JYNNEOS, ACAM2000, and VIGIV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review highlights the pathogenesis of the virus, disease manifestations, drugs, and vaccines that are being used and those under pipeline for the treatment and prevention of Mpox.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 3","pages":"465-478"},"PeriodicalIF":2.9,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472001","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":"Cell–cell communication in stem cells and cancer: Alone but in touch","authors":"Mehran Radak,&nbsp;Hossein Fallahi","doi":"10.1111/fcp.12982","DOIUrl":"10.1111/fcp.12982","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cellular communication and signaling pathways are fundamental regulators of stem cell and cancer cell behaviors. This review explores the intricate interplay of these pathways in governing cellular behaviors, focusing on their implications for diseases, particularly cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This comprehensive review aims to elucidate the significance of cellular signaling pathways in regulating the behavior of stem cells and cancer cells. It delves into the alterations in these pathways, their impact on cell fate, and their implications for developing diseases, notably cancer. The objective is to underscore the importance of understanding these signaling pathways for developing targeted therapeutic strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The review critically analyzes existing literature and research findings concerning the roles of signaling pathways in stem cell behavior regulation, emphasizing their parallels and disparities in cancer cells. It synthesizes information on both direct and indirect modes of cell communication to delineate the complexity of signaling networks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Direct and indirect modes of cell communication intricately regulate the complex signaling pathways governing stem cell behaviors, influencing differentiation potential and tissue regeneration. Alterations in these pathways significantly impact stem cell fate, contributing to disease pathogenesis, including cancer. Understanding these signaling cascades offers insights into developing targeted therapies, particularly cancer treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Understanding the regulation of signaling pathways in stem cells and the specialized subset of cancer stem cells holds promise for innovative therapeutic approaches. By targeting aberrant signaling pathways, tailored interventions may improve treatment outcomes. This review underscores the critical role of signaling pathways in cellular behaviors, offering a pathway toward developing novel, more effective therapies for diverse diseases and disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 3","pages":"479-488"},"PeriodicalIF":2.9,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139476365","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":"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":"38 3","pages":"596-605"},"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":"38 3","pages":"511-522"},"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":"38 3","pages":"410-464"},"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":"38 3","pages":"575-578"},"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":"38 3","pages":"538-549"},"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":"38 3","pages":"588-595"},"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}