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Predictive Biomarkers and Personalized Therapy: Use of Pharmacogenetic Testing in a Scandinavian Perspective
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-19 DOI: 10.1111/bcpt.70009
Niels Westergaard, Trine Meldgaard Lund, Charlotte Vermehren

Precision medicine has significantly advanced through the development of predictive biomarkers based on pharmacogenetic (PGx) testing. These tests identify interactions between drugs and genetic variants that influence patient responses to treatments. Understanding genetic variations in drug-metabolizing enzymes, receptors and transporters and their impact on pharmacokinetics and pharmacodynamics allows for the prediction of drug effects and side effects, enabling tailored treatments for different patient groups. This review focuses on drugs metabolized by cytochrome P450 (CYP450) enzymes, for example, citalopram and clopidogrel or transported by the solute carrier organic anion transporter family member 1B1 (SLCO1B1), for example, atorvastatin and simvastatin, with PGx dosing guidelines, in the context of consumption in Scandinavian countries. A major barrier to the widespread adoption of PGx tests in clinical practice has been healthcare professionals' uncertainty about their efficacy, complexity in result interpretation and questions regarding the evidence base. However, recent studies have demonstrated PGx testing has the potential to improve treatment outcomes, reduce adverse drug reactions and achieve cost savings. These findings underscore the potential of PGx testing as a valuable tool in clinical decision making, promoting its use in a pre-emptive manner to enhance patient care.

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引用次数: 0
Ameliorative Role of β-Caryophyllene on Antioxidant Biomarkers in a Paroxetine-Induced Model of Male Sexual Dysfunction
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-17 DOI: 10.1111/bcpt.70010
Elijah Oluwatosin Olopade, Stephen Adeniyi Adefegha, Jude Oluwapelumi Alao, Ayodeji Emmanuel Adepoju, Aderonke Elizabeth Fakayode, Ganiyu Oboh

Male sexual dysfunction, characterised by reduced libido, ejaculatory issues and erectile dysfunction, often results from oxidative stress and enzymatic imbalance, notably involving phosphodiesterase type 5 (PDE5) and nitric oxide synthase (NOS). This study explores the therapeutic potential of β-caryophyllene (β-CBP), a sesquiterpene with antioxidant and anti-inflammatory properties, in mitigating paroxetine-induced sexual dysfunction in rats. Male Wistar rats were divided into nine treatment groups: control, paroxetine (20 mg/kg/day), sildenafil (20 mg/kg/day), β-CBP (10 mg/kg/day), β-CBP (20 mg/kg/day), paroxetine with β-CBP (10 mg/kg), paroxetine with β-CBP (20 mg/kg), paroxetine with sildenafil and β-CBP with sildenafil. Sexual behavioural assays were evaluated, along with oxidative stress markers, including superoxide dismutase (SOD) and catalase (CAT) activity in penile tissue, assessed using spectrophotometric analysis. CB2 receptor expression was significantly increased in β-CBP-treated groups, suggesting enhanced cannabinoid receptor-mediated signalling, which may be linked to improved erectile function. The effects were dose-dependent, with the 20 mg/kg β-CBP group displaying the most significant improvements. Additionally, β-CBP restored antioxidant enzyme activities, including SOD, CAT and reduced glutathione (GSH) levels in penile tissue, effectively reducing oxidative stress. β-CBP shows promise as a therapeutic agent for male sexual dysfunction by enhancing antioxidative capacity and modulating enzymatic balance.

{"title":"Ameliorative Role of β-Caryophyllene on Antioxidant Biomarkers in a Paroxetine-Induced Model of Male Sexual Dysfunction","authors":"Elijah Oluwatosin Olopade,&nbsp;Stephen Adeniyi Adefegha,&nbsp;Jude Oluwapelumi Alao,&nbsp;Ayodeji Emmanuel Adepoju,&nbsp;Aderonke Elizabeth Fakayode,&nbsp;Ganiyu Oboh","doi":"10.1111/bcpt.70010","DOIUrl":"https://doi.org/10.1111/bcpt.70010","url":null,"abstract":"<p>Male sexual dysfunction, characterised by reduced libido, ejaculatory issues and erectile dysfunction, often results from oxidative stress and enzymatic imbalance, notably involving phosphodiesterase type 5 (PDE5) and nitric oxide synthase (NOS). This study explores the therapeutic potential of β-caryophyllene (β-CBP), a sesquiterpene with antioxidant and anti-inflammatory properties, in mitigating paroxetine-induced sexual dysfunction in rats. Male Wistar rats were divided into nine treatment groups: control, paroxetine (20 mg/kg/day), sildenafil (20 mg/kg/day), β-CBP (10 mg/kg/day), β-CBP (20 mg/kg/day), paroxetine with β-CBP (10 mg/kg), paroxetine with β-CBP (20 mg/kg), paroxetine with sildenafil and β-CBP with sildenafil. Sexual behavioural assays were evaluated, along with oxidative stress markers, including superoxide dismutase (SOD) and catalase (CAT) activity in penile tissue, assessed using spectrophotometric analysis. CB2 receptor expression was significantly increased in β-CBP-treated groups, suggesting enhanced cannabinoid receptor-mediated signalling, which may be linked to improved erectile function. The effects were dose-dependent, with the 20 mg/kg β-CBP group displaying the most significant improvements. Additionally, β-CBP restored antioxidant enzyme activities, including SOD, CAT and reduced glutathione (GSH) levels in penile tissue, effectively reducing oxidative stress. β-CBP shows promise as a therapeutic agent for male sexual dysfunction by enhancing antioxidative capacity and modulating enzymatic balance.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424071","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}
引用次数: 0
Correction to “The Protective Effect of Modafinil on Vincristine-Induced Peripheral Neuropathy in Rats: A Possible Role for TRPA1 Receptors”
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-16 DOI: 10.1111/bcpt.70006

We apologize for the adjustments.

We apologize.

我们对调整表示歉意。
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引用次数: 0
Tetrahydroxy Stilbene Glycoside Reduces Abeta Deposition by Modulating Microglia Activation and via TREM2/PI3K/AKT Pathway in APP/PS1 Mice
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-13 DOI: 10.1111/bcpt.70008
Ming Li, Qihan Song, Shanshan Jie, Chenchen Wang, Can Zhang, Kexin Chi, Yan Gao, Tianzuo Li

Tetrahydroxy stilbene glycoside (TSG), which is the primary active substance of Chinese herbal medicine called Polygonum multiflorum, has been acknowledged to alleviate Alzheimer's disease (AD)-induced learning disorder in the transgene mice. Because the microglia activation is really important during the AD progression, herein, we determined the effects of TSG on AD neuropathology, microglia polarization and its underlying mechanism. We used APP/PS1 mice along with immunohistochemistry and immunofluorescence techniques to evaluate the function of TSG as 60, 120 and 180 mg/kg on Aβ deposition, neuronal loss and microglia polarization induced by AD. Additionally, we assessed the effects of TSG on TREM2 signalling using both molecular docking and Western blot analysis. TSG was found to promote neuronal survival and decrease Aβ deposition in APP/PS1 mice. Moreover, TSG reduced microglia M1 polarization and modulated the TREM2/PI3K/AKT signalling pathways. TSG could reduce neuronal impairment by mediating the microglia polarization by TREM2/PI3K/AKT signalling pathway in APP/PS1 mice and is a latent pharmacological research direction for the therapy in the patients with AD.

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引用次数: 0
Could Flumazenil Be Used Pre-hospital by Intramuscular Injection for Coma due to Mixed Drug Overdose Not Responding to Naloxone?: A Systematic Review of the Evidence
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-13 DOI: 10.1111/bcpt.70007
Ilinca Farcas, Lisa Schölin, Michael Eddleston

Background/Rationale

Benzodiazepine-involved overdose deaths are increasing. Flumazenil is rarely used due to fear of seizures; however, the risk benefit may favour its use. Flumazenil is licensed for intravenous (IV) use, but intramuscular (IM) treatment would be required pre-hospital.

Objective

To identify and synthesise pre-clinical and clinical data on the parenteral IM flumazenil safety and efficacy.

Methods

PubMed, Google Scholar, Cochrane and Scopus searches without any language restriction. Adverse effect studies were limited to systematic reviews and large cohort studies (n > 100), IM administration efficacy to studies in large animal (mammalian, excluding reptiles and birds) and humans.

Results

Two systematic reviews reported adverse effects from IV or IM flumazenil in clinical use and combined retrospective/prospective patient cohort. Seizures were uncommon (< 2%) including mixed overdoses. Seven studies (four animal, three human) reported on IM flumazenil. Animal studies indicated IM flumazenil efficacy. In a canine cross-over study, IM flumazenil reversed midazolam sedation moderately slower than IV. Two clinical observational studies reported sedation reversal with IM flumazenil, whereas a cross-over study found no IM flumazenil response at 15 min.

Conclusion

IM flumazenil data are sparse, but it may be effective and safe. Clinical research is urgently needed to determine whether pre-hospital IM flumazenil can prevent benzodiazepine-involved overdose deaths.

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引用次数: 0
Promoting Resiliency to Stress in the Vascular Endothelium
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-12 DOI: 10.1111/bcpt.70001
Maria J. Jaramillo-Torres, Rachel H. Limpert, William J. Butak, Katie E. Cohen, Alicen A. Whitaker-Hilbig, Matthew J. Durand, Julie K. Freed, Gopika SenthilKumar

By 2050, roughly 60% of the population will have cardiovascular disease. While a substantial amount of data has been generated over the last few decades that has aided in our understanding of cardiovascular disease pathology, less is known about how to increase resiliency to cardiovascular risk factors that individuals are exposed to on a daily basis. The vascular endothelium is considered the first line of defence against circulating noxious stimuli and, when dysfunctional, is an early risk factor for the development of cardiovascular disease. A vast amount of data has been generated demonstrating how external stress impairs the vascular endothelium; however, there is a paucity of knowledge regarding how to amplify protective pathways and ward off stress and the development of disease, which is the focus of this review. Targeting known protective endothelial pathways may be feasible to increase resiliency to vascular stress. Leveraging stress to boost defence mechanisms within the vascular endothelium is also proposed and may help identify novel therapeutic targets to protect individuals from the stress of everyday life.

{"title":"Promoting Resiliency to Stress in the Vascular Endothelium","authors":"Maria J. Jaramillo-Torres,&nbsp;Rachel H. Limpert,&nbsp;William J. Butak,&nbsp;Katie E. Cohen,&nbsp;Alicen A. Whitaker-Hilbig,&nbsp;Matthew J. Durand,&nbsp;Julie K. Freed,&nbsp;Gopika SenthilKumar","doi":"10.1111/bcpt.70001","DOIUrl":"https://doi.org/10.1111/bcpt.70001","url":null,"abstract":"<p>By 2050, roughly 60% of the population will have cardiovascular disease. While a substantial amount of data has been generated over the last few decades that has aided in our understanding of cardiovascular disease pathology, less is known about how to increase resiliency to cardiovascular risk factors that individuals are exposed to on a daily basis. The vascular endothelium is considered the first line of defence against circulating noxious stimuli and, when dysfunctional, is an early risk factor for the development of cardiovascular disease. A vast amount of data has been generated demonstrating how external stress impairs the vascular endothelium; however, there is a paucity of knowledge regarding how to amplify protective pathways and ward off stress and the development of disease, which is the focus of this review. Targeting known protective endothelial pathways may be feasible to increase resiliency to vascular stress. Leveraging stress to boost defence mechanisms within the vascular endothelium is also proposed and may help identify novel therapeutic targets to protect individuals from the stress of everyday life.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389118","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}
引用次数: 0
Effects of GLP-1 Receptor Agonists in Alcohol Use Disorder
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1111/bcpt.70004
Mette Kruse Klausen, Gitte Moos Knudsen, Tina Vilsbøll, Anders Fink-Jensen

In the search for novel treatment strategies for alcohol use disorder (AUD), glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) approved for treating Type 2 diabetes and obesity have caught much attention. GLP-1 is a naturally occurring peptide produced in the small intestines and the brain, regulating plasma glucose levels and satiety. This focused review will report on the preclinical studies, case stories, register-based cohort studies, brain-imaging data and secondary analysis of clinical data supporting the role of GLP-1RAs as a novel treatment of AUD. Several clinical trials are ongoing, examining the potential effects of the GLP-1RA semaglutide in AUD.

{"title":"Effects of GLP-1 Receptor Agonists in Alcohol Use Disorder","authors":"Mette Kruse Klausen,&nbsp;Gitte Moos Knudsen,&nbsp;Tina Vilsbøll,&nbsp;Anders Fink-Jensen","doi":"10.1111/bcpt.70004","DOIUrl":"10.1111/bcpt.70004","url":null,"abstract":"<p>In the search for novel treatment strategies for alcohol use disorder (AUD), glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) approved for treating Type 2 diabetes and obesity have caught much attention. GLP-1 is a naturally occurring peptide produced in the small intestines and the brain, regulating plasma glucose levels and satiety. This focused review will report on the preclinical studies, case stories, register-based cohort studies, brain-imaging data and secondary analysis of clinical data supporting the role of GLP-1RAs as a novel treatment of AUD. Several clinical trials are ongoing, examining the potential effects of the GLP-1RA semaglutide in AUD.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073577","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}
引用次数: 0
Fluvoxamine Inhibited NLRP3 and NF-κB Inflammatory Pathways and Maintained Genital Functions by Ameliorating CD-MPR, KISS-1, AQP4 and Claudin-1 Expressions
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1111/bcpt.70000
Senay Topsakal, Ozlem Ozmen, Kadriye Nilay Ozcan, Halil Asci, Orhan Berk Imeci, Mehmet Abdulkadir Sevuk, Pinar Aslan Kosar

Fluvoxamine (FLV), a selective serotonin reuptake inhibitor, is commonly used to treat anxiety, major depressive disorder and obsessive-compulsive disorder, among other psychiatric conditions. This study aims to evaluate the effectiveness of FLV in mitigating damage caused by lipopolysaccharide (LPS) to the female genital tract. Thirty-two female Wistar Albino rats were randomly divided into four groups: control, LPS, LPS-FLV and FLV. At the end of the experimental period, tissues from the ovaries, fallopian tubes and uterus were collected for histological, immunohistochemical and genetic analyses. Histological examination of the LPS group revealed mild to moderate bleeding, oedema and neutrophil infiltration. Additionally, there were signs of endometrial damage in the uterus and loss of cilia in the fallopian tubes. Immunohistochemical analysis showed that LPS increased the expressions of nuclear factor kappa beta (NF-κB) and cation-dependent mannose 6-phosphate receptors (CD-MPR) and reduced kisspeptin-1 (KISS-1) expression. Genetic analysis indicated that LPS increased the expression of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) and aquaporin4 (AQP4) genes while decreasing Claudin-1 expression. However, all these adverse effects were reversed by FLV treatment. The study's findings suggest that FLV may be beneficial in treating LPS-induced damage to the female reproductive system.

{"title":"Fluvoxamine Inhibited NLRP3 and NF-κB Inflammatory Pathways and Maintained Genital Functions by Ameliorating CD-MPR, KISS-1, AQP4 and Claudin-1 Expressions","authors":"Senay Topsakal,&nbsp;Ozlem Ozmen,&nbsp;Kadriye Nilay Ozcan,&nbsp;Halil Asci,&nbsp;Orhan Berk Imeci,&nbsp;Mehmet Abdulkadir Sevuk,&nbsp;Pinar Aslan Kosar","doi":"10.1111/bcpt.70000","DOIUrl":"10.1111/bcpt.70000","url":null,"abstract":"<p>Fluvoxamine (FLV), a selective serotonin reuptake inhibitor, is commonly used to treat anxiety, major depressive disorder and obsessive-compulsive disorder, among other psychiatric conditions. This study aims to evaluate the effectiveness of FLV in mitigating damage caused by lipopolysaccharide (LPS) to the female genital tract. Thirty-two female Wistar Albino rats were randomly divided into four groups: control, LPS, LPS-FLV and FLV. At the end of the experimental period, tissues from the ovaries, fallopian tubes and uterus were collected for histological, immunohistochemical and genetic analyses. Histological examination of the LPS group revealed mild to moderate bleeding, oedema and neutrophil infiltration. Additionally, there were signs of endometrial damage in the uterus and loss of cilia in the fallopian tubes. Immunohistochemical analysis showed that LPS increased the expressions of nuclear factor kappa beta (NF-κB) and cation-dependent mannose 6-phosphate receptors (CD-MPR) and reduced kisspeptin-1 (KISS-1) expression. Genetic analysis indicated that LPS increased the expression of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) and aquaporin4 (AQP4) genes while decreasing Claudin-1 expression. However, all these adverse effects were reversed by FLV treatment. The study's findings suggest that FLV may be beneficial in treating LPS-induced damage to the female reproductive system.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073588","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}
引用次数: 0
In Vivo Investigation of the Effects of Nonylphenol on the Pituitary–Adrenal Axis and Pineal Gland in Male Rats
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-31 DOI: 10.1111/bcpt.70003
E. N. İnkaya, E. Tokgöz, N. Barlas

The pineal gland secretes melatonin, which regulates various physiological processes; damage to this gland disrupts these functions. This study aimed to investigate the effect of nonylphenol on the pineal gland and the pituitary–adrenal axis, which is associated with this system. The study was initiated using Wistar albino male rats on their postnatal 21st day, a critical developmental stage for endocrine regulation. Nonylphenol was administered via oral gavage at doses of 5, 25 and 125 mg/kg/day, while bisphenol-A was given at 50 mg/kg/day as a positive control. At the end of the treatment period, liver, kidney, pituitary, pineal and adrenal tissues were examined histopathologically. Hormone levels were analysed in serum samples. Significant changes in adrenocorticotropic hormone, melatonin and aldosterone levels were detected in hormone analyses. In contrast, no differences in corticosterone and glucose levels were detected. Histopathological findings showed structural changes in tissues. The effects of nonylphenol on the pituitary–adrenal axis and melatonin vary depending on the experimental protocols employed. However, it is clear that nonylphenol and bisphenol A have negative effects on the pituitary–adrenal axis, pineal gland, liver and kidney. In conclusion, future research should focus on elucidating the molecular mechanisms underlying these effects and developing environmentally friendly strategies to eliminate nonylphenol and bisphenol-A contamination.

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引用次数: 0
Addressing Improper Medicine Storage Practices: Commentary on Louhisalmi et  al.'s Study
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-25 DOI: 10.1111/bcpt.70005
Shu-Wen Cheng, Lien-Chung Wei
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引用次数: 0
期刊
Basic & Clinical Pharmacology & Toxicology
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