Filip Stefanovic, Andres Gomez-Caminero, David M Jacobs, Poornima Subramanian, Igor Puzanov, Maya R Chilbert, Steven G Feuerstein, Yan Yatsynovich, Benjamin Switzer, Jerome J Schentag
{"title":"Neural Net Modeling of Checkpoint Inhibitor Related Myocarditis and Steroid Response.","authors":"Filip Stefanovic, Andres Gomez-Caminero, David M Jacobs, Poornima Subramanian, Igor Puzanov, Maya R Chilbert, Steven G Feuerstein, Yan Yatsynovich, Benjamin Switzer, Jerome J Schentag","doi":"10.2147/CPAA.S369008","DOIUrl":"https://doi.org/10.2147/CPAA.S369008","url":null,"abstract":"<p><strong>Background: </strong>Serious but rare side effects associated with immunotherapy pose a difficult problem for regulators and practitioners. Immune checkpoint inhibitors (ICIs) have come into widespread use in oncology in recent years and are associated with rare cardiotoxicity, including potentially fatal myocarditis. To date, no comprehensive model of myocarditis progression and outcomes integrating time-series based laboratory and clinical signals has been constructed. In this paper, we describe a time-series neural net (NN) model of ICI-related myocarditis derived using supervised machine learning.</p><p><strong>Methods: </strong>We extracted and modeled data from electronic medical records of ICI-treated patients who had an elevation in their troponin. All data collection was performed using an electronic case report form, with approximately 300 variables collected on as many occasions as available, yielding 6000 data elements per patient over their clinical course. Key variables were scored 0-5 and sequential assessments were used to construct the model. The NN model was developed in MatLab and applied to analyze the time course and outcomes of treatments.</p><p><strong>Results: </strong>We identified 23 patients who had troponin elevations related to their ICI therapy, 15 of whom had ICI-related myocarditis, while the remaining 8 patients on ICIs had other causes for troponin elevation, such as myocardial infarction. Our model showed that troponin was the most predictive biomarker of myocarditis, in line with prior studies. Our model also identified early and aggressive use of steroid treatment as a major determinant of survival for cases of grade 3 or 4 ICI-related myocarditis.</p><p><strong>Conclusion: </strong>Our study shows that a supervised learning NN can be used to model rare events such as ICI-related myocarditis and thus provide clinical insight into drivers of progression and treatment outcomes. These findings direct attention to early detection biomarkers and clinical symptoms as the best means of implementing early and potentially life-saving steroid treatment.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"14 ","pages":"69-90"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/8c/cpaa-14-69.PMC9376002.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10589798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Assessing Efficacy and Safety of a Novel Low-Dose Turmeric Extract Formulation in Healthy Adults with Chronic Knee Pain.","authors":"Shefali Thanawala, Rajat Shah, Venkateswarlu Somepalli, KrishnaRaju Venkata Alluri, Prabakaran Desomayanandam, Arun Bhuvanendran","doi":"10.2147/CPAA.S307464","DOIUrl":"10.2147/CPAA.S307464","url":null,"abstract":"<p><strong>Background: </strong>Knee pain causes functional limitations, eventually compromising the quality of life. We evaluated the efficacy of our water-dispersible turmeric formulation (60% natural curcuminoids, TurmXTRA 60N<sup>®</sup>-WDTE60N), which exhibited better PK profile at low dose (250 mg) than standard turmeric extract, in alleviating symptoms of chronic knee pain.</p><p><strong>Methods: </strong>In this randomized, double-blind, placebo-controlled trial, subjects received either 250 mg WDTE60N capsule (150 mg curcuminoids; n = 53) or appearance-matched placebo capsule (n = 53) once daily for 90 days. Primary endpoint was change in pain score on the visual analogue scale (VAS) after 80-m fast-paced walk test.</p><p><strong>Results: </strong>A total of 96 subjects completed the study. WDTE60N reduced VAS score from baseline (5.4 ± 0.9) to day 90 (3.8 ± 0.8) with greater mean reduction than placebo (-1.5 ± 0.7 vs -0.6 ± 0.8, <i>p</i> < 0.0001; 2.5 times). It also significantly improved the time taken for 80-m fast-paced walk test and 9-step stair-climb test; and improved all biomarkers compared to placebo (<i>p</i> > 0.05). Three adverse events occurred but were unrelated to study products.</p><p><strong>Conclusion: </strong>WDTE60N 250 mg administered once daily for 3 months, alleviated knee pain, improved joint function in healthy subjects with chronic knee pain, was well tolerated and safe.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"13 ","pages":"91-100"},"PeriodicalIF":3.1,"publicationDate":"2021-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/ad/cpaa-13-91.PMC8149286.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9727011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Wound Healing Effect of <i>Acokanthera schimperi</i> Schweinf (Apocynaceae) Methanol Leaf Extract Ointment in Mice and Its in-vitro Antioxidant Activity.","authors":"Belete Kassa Alemu, Desye Misganaw, Getnet Mengistu","doi":"10.2147/CPAA.S288394","DOIUrl":"https://doi.org/10.2147/CPAA.S288394","url":null,"abstract":"<p><strong>Background: </strong><i>Acokanthera schimperi</i> is traditionally used for the treatment of wounds and various bacterial infections. Due to the ongoing escalation of antimicrobial resistance, there is an increasing demand for the appropriate wound care and hence, the present study was initiated to investigate the wound healing effects of the leaf extract ointments of <i>A. schimperi</i> in mice and its in-vitro antioxidant activity.</p><p><strong>Methods: </strong>The crude extract was prepared as 5% and 10% w/w ointments for topical use in mice. Wound contraction and epithelialization period were determined in excision and infected models, whereas tensile strength was determined in an incision model. Besides, its antioxidant activity was evaluated using the DPPH method.</p><p><strong>Results: </strong>In this study, the 10% w/w extract ointment did not cause toxicity at the 2000 mg/kg limit dose. In the excision model, the 10% w/w ointment exhibited a significant wound contraction effect starting from day 6 to 14 with a complete epithelization shown on day 13. Besides, the 5%w/w ointment showed a significant wound contraction effect starting from day 6 onwards, and a significant decrease in the epithelization period observed on day 16. Conversely, both the 10% w/w and 5% w/w ointments showed significant wound contraction effects starting from day 4 and onwards in the infected model. However, a complete epithelization period was observed on days 14 and 18 in the 10%w/w and 5% w/w/extract ointment treated groups, respectively. In the incision model, the 10% (w/w) and 5% (w/w) extract ointments showed a significant increase in tensile strength by 36.80 and 32.23%, respectively. Moreover, the antioxidant activity of the extract was concentration-dependent with an IC50 value of 5.49± 0.38 µg/µL.</p><p><strong>Conclusion: </strong>The potential wound healing effects of this plant may provide a candidate source in the discovery of new drugs for the treatment of wounds.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"213-222"},"PeriodicalIF":2.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/c6/cpaa-12-213.PMC7780988.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38791306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An Up-to-Date Overview of Therapeutic Agents for the Treatment of COVID-19 Disease.","authors":"Tafere Mulaw Belete","doi":"10.2147/CPAA.S284809","DOIUrl":"10.2147/CPAA.S284809","url":null,"abstract":"<p><p>Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a great potential to overwhelm the world healthcare systems that may lead to high morbidity and mortality. It also affects world economic development in the future. Currently, no proven effective drugs or vaccines are available for the management of COVID-19 disease. The pace of normal drug development progression is unacceptable in the context of the current pandemic. Therefore, repurposing the existing drugs that were used for the treatment of malaria, Ebola, and influenza helps rapid drug development for COVID-19. Currently, several repurposing candidate drugs are in a clinical trial including, chloroquine monoclonal antibodies, convalescent plasma, interferon, and antiviral therapies. Antiviral drugs like arbidol, remdesiv and favirnavir are the most promising due to the similarities of the viruses regarding viral entry, fusion, uncoating, and replication. This review article provides an overview of the potential therapeutic agent, which displayed better clinical treatment outcomes. Moreover, with further understanding of the SARS-CoV-2 virus, new drugs targeting specific SARS-CoV-2 viral components arise, and investigations on these novels anti-SARSCoV- 2 agents are also reviewed.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"203-212"},"PeriodicalIF":2.0,"publicationDate":"2020-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/3f/cpaa-12-203.PMC7753885.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38750941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Constantine E Kosmas, Andreas Skavdis, Andreas Sourlas, Evangelia J Papakonstantinou, Edilberto Peña Genao, Rogers Echavarria Uceta, Eliscer Guzman
{"title":"Safety and Tolerability of PCSK9 Inhibitors: Current Insights.","authors":"Constantine E Kosmas, Andreas Skavdis, Andreas Sourlas, Evangelia J Papakonstantinou, Edilberto Peña Genao, Rogers Echavarria Uceta, Eliscer Guzman","doi":"10.2147/CPAA.S288831","DOIUrl":"https://doi.org/10.2147/CPAA.S288831","url":null,"abstract":"<p><p>The current era of preventive cardiology continues to emphasize on low-density lipoprotein cholesterol (LDL-C) reduction to alleviate the burden of atherosclerotic cardiovascular disease (ASCVD). In this regard, the pharmacological inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme via monoclonal antibodies has emerged as a novel lipid-lowering therapy, leading to a marked reduction in circulating LDL-C levels and subsequent improvement of cardiovascular outcomes. As these agents are increasingly used in current clinical practice, mounting scientific and clinical evidence supports that PCSK9 inhibitors offer an excellent safety and tolerability profile with a low incidence of adverse events. Notably, the most frequently reported side effects are injection-site reactions. In contrast to statins, PCSK9 inhibitors do not appear to exert a detrimental effect on glycemic control or to increase the incidence of new-onset diabetes mellitus. Accumulating evidence also indicates that PCSK9 inhibitors are a safe, well-tolerated and effective therapeutic strategy for patients with statin intolerance. On the other hand, as PCSK9 inhibitors reduce LDL-C to unprecedented low levels, a large body of current research has examined the effects of their long-term administration on neurocognition and on levels of vitamin E and other fat-soluble vitamins, providing encouraging results. This review aims to present and discuss the current clinical and scientific evidence pertaining to the safety and tolerability of PCSK9 inhibitors.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"191-202"},"PeriodicalIF":2.0,"publicationDate":"2020-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S288831","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38386556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael Z Liao, Johannes Kast, Marloes Berkhout, Hans Prenen, Sandeep Dutta, Vijay V Upreti
{"title":"Is Bodyweight-Based Dosing Truly Better Than Flat Dosing for Panitumumab? [Response to Letter].","authors":"Michael Z Liao, Johannes Kast, Marloes Berkhout, Hans Prenen, Sandeep Dutta, Vijay V Upreti","doi":"10.2147/CPAA.S289793","DOIUrl":"https://doi.org/10.2147/CPAA.S289793","url":null,"abstract":"","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"189-190"},"PeriodicalIF":2.0,"publicationDate":"2020-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/42/cpaa-12-189.PMC7734040.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38722248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Psychotropic Medications-Induced Tardive Dyskinesia and Associated Factors Among Patients with Mental Illness in Ethiopia.","authors":"Assefa Kumsa, Shimelis Girma, Bezaye Alemu, Liyew Agenagnew","doi":"10.2147/CPAA.S285585","DOIUrl":"10.2147/CPAA.S285585","url":null,"abstract":"<p><strong>Background: </strong>Tardive dyskinesia (TD) remains a significant burden especially among patients taking psychotropic medications, and it is associated with adverse effects that can lead to subjective suffering, stigma, poor compliance to medication, and poor quality of life. However, it is unrecognized and overlooked in clinical settings. So, this study aimed to assess the magnitude of tardive dyskinesia and associated factors among mentally ill patients attending follow-up treatment at Jimma University Medical Center Psychiatry clinic, Jimma, Southwest Ethiopia, 2019.</p><p><strong>Methods: </strong>Institutional-based cross-sectional study design was conducted in 417 samples. Participants were selected by systematic random sampling techniques. Data were collected by a semi-structured interviewer-administered questionnaire, and the document was reviewed to obtain the patient's profile. Tardive dyskinesia was assessed by using the Extrapyramidal Symptom Rating Scale after informed consent was obtained from respondents. Data entry was done by EpiData version 3.1, and analysis was done by using SPSS 22.0 statistical software. Binary logistic regression and multivariate logistic regression were used to see the association and to identify independent factors at a p-value of <0.05.</p><p><strong>Results: </strong>Prevalence of drug-induced tardive dyskinesia was 15.4% (CI 95%: 12.0, 19.3). Female, age range between 30 and 44 years, having a diagnosis of major depressive disorder with the psychotic feature, taking chlorpromazine equivalent dose ˃600mg, and taking anticholinergic medications were variables positively associated with tardive dyskinesia, whereas cigarette smoking was negatively associated with tardive dyskinesia.</p><p><strong>Conclusion: </strong>The prevalence of drug-induced tardive dyskinesia in this study was high. Prescribing medications less than 600mg equivalent dose of chlorpromazine, giving attention for female patients, patients having a diagnosis of major depressive disorder, and reducing giving anticholinergic medications will be important measures for clinicians to reduce the occurrence of tardive dyskinesia.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"179-187"},"PeriodicalIF":2.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/14/cpaa-12-179.PMC7719051.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38700706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeroen J M A Hendrikx, Jos H Beijnen, Alwin D R Huitema
{"title":"Is Bodyweight-Based Dosing Truly Better Than Flat Dosing for Panitumumab? [Letter].","authors":"Jeroen J M A Hendrikx, Jos H Beijnen, Alwin D R Huitema","doi":"10.2147/CPAA.S282866","DOIUrl":"https://doi.org/10.2147/CPAA.S282866","url":null,"abstract":"1Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; 2Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands; 3Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands Dear editor With great interest we read the paper by Liao et al in which they compared a 2-weekly bodyweight-based (6 mg/kg) and fixed (480 mg) administration of panitumumab, a monoclonal antibody (Mab) binding the EGFR receptor. The authors used a population pharmacokinetics model to simulate pharmacokinetics of 1200 virtual individuals for each strategy. The observed interpatient variability in mean simulated AUC (CVAUCmean) was compared and was 34% (fixed dosing) versus 29% (bodyweight-based dosing). Based on this, the authors concluded for panitumumab that “body weight-based approach is the recommended patient dosing strategy”. Previously, we assessed feasibility of fixed dosing as an alternative strategy for thirteen Mabs including panitumumab. We concluded that fixed dosing is a more rational approach as pharmacodynamics (efficacy and toxicity) of antagonistic Mabs are not concentration-related at concentrations exceeding the minimum target inhibitory concentration (ICmin). For panitumumab, the estimated threshold is 3.83 μg/mL. The authors compared the CVAUCmean of both dosing strategies. However, because of the ICmin, trough levels (Cmin) would be a better parameter for assessing efficacy of panitumumab. Although the observed Cmin after bodyweight-based dosing is reported (Figure 1 and Discussion), we miss report of simulated Cmin of the fixed dosing schedule. As the lowest interquartile AUC after fixed and bodyweight-based dosing of panitumumab is comparable (987 versus 908 μg*d/ mL, respectively, in Table 2), it is likely that Cmin of the both strategies is comparable (~20–30 μg/mL and »ICmin) and, therefore, both strategies have equivalent efficacy. The reported difference in CVAUCmean for both dosing strategies is mainly caused by the higher exposure of panitumumab in patients with a low bodyweight after fixed dosing (Figure 2). This results in a difference between the highest interquartile AUC after fixed and bodyweight-based dosing (1582 versus 1254 μg*d/mL, respectively in Table 2). However, this is clinically irrelevant as for panitumumab (like most Mabs in oncology), an exposure-toxicity relationship is absent. Although increased incidence of skin toxicity has been reported with increasing doses, this is related to the EGFR inhibition and reaches a plateau at doses of ≥2.5 mg/kg. As onset of ≥grade 2 toxicity is related to better survival and is a result of target inhibition, it even may be evaluated as biomarker for efficacy. In fact, the manufacturer reports that doses up to 12 mg/kg have been used and that the safety profile was consistent with the recommended dose. Since Correspondence: Jeroen JMA Hendrikx Department of ","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"177-178"},"PeriodicalIF":2.0,"publicationDate":"2020-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f1/ba/cpaa-12-177.PMC7610198.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38578692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Majed M Masadeh, Karem H Alzoubi, Bashar M Al-Taani, Majd M Masadeh, Zainah O Aburashed, Nasr Alrabadi
{"title":"Vitamin D Pretreatment Attenuates Ciprofloxacin-Induced Antibacterial Activity.","authors":"Majed M Masadeh, Karem H Alzoubi, Bashar M Al-Taani, Majd M Masadeh, Zainah O Aburashed, Nasr Alrabadi","doi":"10.2147/CPAA.S268330","DOIUrl":"https://doi.org/10.2147/CPAA.S268330","url":null,"abstract":"<p><strong>Background: </strong>Ciprofloxacin is an antimicrobial that is commonly used to treat several types of infections. It exerts its antimicrobial activity through interfering with bacterial DNA replication and transcription, leading to increase oxidative stress and eventually bacterial death. Vitamin D, on the other hand, has been found to have DNA protective and antioxidant effects. In the current study, the possible interactive effect of vitamin D on ciprofloxacin-induced cytotoxicity was investigated in various standard bacterial strains.</p><p><strong>Methods: </strong>The bacterial strains that were used include <i>Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Acinetobacter baumannii, Proteus mirabilis</i>, and <i>Klebsiella pneumoniae</i>. The antibacterial effect of ciprofloxacin with and without vitamin D treatment of the bacteria was assessed using disc diffusion method and by measuring the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. Moreover, reactive oxygen species (ROS) generation after pretreatment of <i>E. Coli</i> cells with ciprofloxacin and/or vitamin D was measured as a function of as a function of hydrogen peroxide generation.</p><p><strong>Results: </strong>Ciprofloxacin demonstrated a potent antibacterial effect against the tested strains of bacteria. Moreover, pretreatment with vitamin D resulted in protecting the bacteria from the cytotoxicity of ciprofloxacin, this was indicated by the significantly smaller zones of inhibition and higher MIC values compared to ciprofloxacin alone as well as reduced ciprofloxacin-induced ROS generation after treatment with vitamin D.</p><p><strong>Conclusion: </strong>Results revealed the possible reduction in the activity of ciprofloxacin when used in combination with vitamin D. This could be explained by the ability of vitamin D to reduce oxidative stress in the bacterial cells.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"171-176"},"PeriodicalIF":2.0,"publicationDate":"2020-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S268330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38643093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypoglycemic and Antihyperglycemic Activities of 80% Methanol Root Extract of <i>Acanthus polystachyus</i> Delile (Acanthaceae) in Type 2 Diabetic Rats.","authors":"Dagninet Derebe, Muluken Wubetu, Amare Alamirew","doi":"10.2147/CPAA.S273501","DOIUrl":"https://doi.org/10.2147/CPAA.S273501","url":null,"abstract":"<p><strong>Background: </strong>The morbidity and mortality rate from diabetic mellitus are increasing in the world especially in low- and middle-income countries; hence, it is necessary to evaluate the efficacy and safety of medicinal plants to support existing drugs in treating diabetes mellitus. Therefore, the aim of this study was to evaluate the hypoglycemic effect of 80% methanol root extract of <i>Acanthus polystachyus</i> in normoglycemic, hyperglycemic, and streptozotocin-nicotinamide induced diabetic rats.</p><p><strong>Methods: </strong>Male albino Wistar rats were divided into five groups (n=6) in all three models. In all models, group one rats served as a negative control and were received vehicle (10mL/kg distilled water), whereas group two (APRE100), three (APRE200), and four (APRE400) were treated with 100, 200, and 400mg/kg of extract, respectively, and group five were treated with glibenclamide (5mg/kg) and served as a positive control. Blood glucose levels were measured at different time points by taking blood from their tails. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test to carry out comparisons between and within-group and P < 0.05 was considered as statistically significant.</p><p><strong>Results: </strong>The root of <i>Acanthus polystachyus</i> reduces peak blood sugar levels significantly after the loading of oral glucose at all tested doses. In streptozotocin-nicotinamide-induced type 2 diabetic rats, the daily oral administration of the crude extracts showed a significant reduction of blood glucose level at all tested doses compared to the negative control group. However, the extract did not reduce blood glucose levels in normoglycemic rats at all tested doses compared to both negative and positive control.</p><p><strong>Conclusion: </strong>From this study, it can be concluded that the root extract of <i>Acanthus polystachyus</i> showed an antihyperglycemic effect in hyperglycemic and diabetic rats but lack hypoglycemic effect in normoglycemic rats. Hence, the plant root may be a good candidate for the development of new antidiabetic drugs.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"149-157"},"PeriodicalIF":2.0,"publicationDate":"2020-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S273501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38492509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}