Current clinical pharmacology最新文献

{"title":"Impact of Ondansetron on Withdrawal Signs, Fentanyl Requirement and Pain Relief in Opioid-addicted Patients under General Anesthesia.","authors":"Farzaneh Mahikhan,&nbsp;Morteza Hashemian,&nbsp;Tania Dehesh,&nbsp;Elham Jafari,&nbsp;Mandana Jafari,&nbsp;Hamid-Reza Rahimi","doi":"10.2174/1574884714666190131122846","DOIUrl":"https://doi.org/10.2174/1574884714666190131122846","url":null,"abstract":"<p><strong>Background: </strong>Serotonin 5-HT3 receptor antagonists such as ondansetron have been investigated to attenuate opioid withdrawal signs in studies.</p><p><strong>Objective: </strong>Therefore, we designed a randomized double-blinded placebo-controlled trial to evaluate this effect on opioid-addicted patients who were admitted to the orthopedic department for surgery due to bone fractures.</p><p><strong>Methods: </strong>Male adults who were addicted to opioids, aged 18 to 79 years were enrolled (n=96) and randomized into intravenous doses (4 & 8 mg) of ondansetron (n=32) and placebo (n=32). The vital signs, withdrawal symptoms and the frequency requirement of fentanyl were recorded during anesthesia, and opioid (pethidine) analgesic was received during the recovery period. Outcome parameters were analyzed for reduction of withdrawal symptoms in addicted adults.</p><p><strong>Results: </strong>We indicated that ondansetron demonstrated significant differences with few vital outcomes including systolic blood pressure (SBP) 20 (SBP3) and 50 min (SBP4) after injection of ondansetron during the period of surgery. Ondansetron could also significantly reduce the frequency requirement of fentanyl at 20 min (dose 3) in general anesthesia. Furthermore, requirement for further administration of opioid analgesic drugs such as pethidine was significantly reduced in the ondansetron groups. Objective opioid withdrawal scale (OOWS) results indicated that few clinical parameters including tremor, hot and cold flushes and anxiety were significantly attenuated in addicted patients who received ondansetron.</p><p><strong>Conclusion: </strong>This study demonstrated supporting evidence for the beneficial treatment of ondansetron for the control of withdrawal symptoms and pain in addicted patients, and more clinical studies are suggested in this regard.</p>","PeriodicalId":10746,"journal":{"name":"Current clinical pharmacology","volume":"14 3","pages":"232-241"},"PeriodicalIF":3.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574884714666190131122846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36966817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Added Value of Liquid Antipsychotics: The Case of Quetiapine.","authors":"Georgios Papazisis,&nbsp;Spyridon Siafis","doi":"10.2174/1574884713666181102145236","DOIUrl":"https://doi.org/10.2174/1574884713666181102145236","url":null,"abstract":"<p><strong>Background: </strong>Antipsychotic drugs are the cornerstone of schizophrenia treatment and are also indicated for other psychotic and mood disorders. Different antipsychotic drugs and their formulations are available, though liquid forms have been overlooked.</p><p><strong>Methods: </strong>Herein the added value of liquid antipsychotics is reviewed, with a focus on the recently introduced liquid quetiapine, a frequently used antipsychotic.</p><p><strong>Results: </strong>Liquid antipsychotics are easily administrated via the preferable oral route, while compliance under supervised administration is transparent. Liquid forms could be preferred in patients with swallowing difficulties, which are common in elderly patients and often concealed. In this population, the availability of liquid antipsychotics could prevent errors in medication administration, which could possibly render caregivers labile to any harm caused to the patient. Aspiration, however, remains a risk with liquid formulations. Common errors in medication administration are the omission of treatment and alteration of solid oral formulations. Regarding quetiapine, omission of treatment could be associated with non-adherence as well as discontinuation symptoms, while alteration of extended release formulation could alter its pharmacokinetics. Mildly agitated and cooperative patients are another target population of liquid antipsychotics, which can induce fast sedation avoiding involuntary intramuscular injections. The combination of sedative properties and low incidence of extrapyramidal symptoms makes liquid quetiapine a valuable option for these patients, yet the current evidence is limited.</p><p><strong>Conclusion: </strong>The liquid form of quetiapine can facilitate pharmacotherapy of schizophrenia and can be defined as value added medicine bringing key benefits not only to the patients and caregivers but also to the health care system.</p>","PeriodicalId":10746,"journal":{"name":"Current clinical pharmacology","volume":"14 2","pages":"101-107"},"PeriodicalIF":3.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574884713666181102145236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36628832","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":"Desensitization of 5-HT-1A Somatodentritic Receptors in Tryptophan Treated and Co-treated Rats Induced by Methylphenidate.","authors":"Muhammad Farhan,&nbsp;Fatima Riaz,&nbsp;Sana Wali,&nbsp;Hamna Rafiq","doi":"10.2174/1574884713666181112123309","DOIUrl":"https://doi.org/10.2174/1574884713666181112123309","url":null,"abstract":"<p><strong>Background: </strong>Psychostimulants can induce behavioral sensitization by their chronic use. The main target for the action of these drugs is dopamine, neither epinephrine nor serotonin transporters. Serotonin is synthesized by the precursor L-tryptophan. Tryptophan and methylphenidate being 5-HT agonists, both increase the level of serotonin thereby causing desensitization of 5-HT1a receptors. The present study investigated whether behavioral sensitization induced by Methylphenidate is decreased in tryptophan administrated animals.</p><p><strong>Methods: </strong>The Experiment was divided into 2 phases (1). Behavioral effects of repeated administration of TRP 100 mg/kg and MPD for 14 days in three groups; (i) water (ii) MPD 1.0 mg/kg (iii) TRP. To explore the locomotor effects of treatment, the activity was monitored in a familiar and novel environment. (2) Behavioral consequences of repeatedly administrated MPD (1.0 mg/kg) on pretreated TRP (100 mg/kg) and MPD (1.0 mg/kg) animals following Co-MPD and TRP for 14 days, rats were divided in three groups (i) water, (ii) MPD and (iii) TRP as mentioned in Experiment no 1. After two weeks six subgroups were assigned i.e. (i) water-saline, (ii) water- MPD, (iii) TRP-saline (iv) TRP-MPD (v) MPD-saline and (vi) MPD-MPD+TRP and treated for further 14 days. Locomotor behavior was monitored in familiar environment on the next day and in novel environment on alternate days of each administration.</p><p><strong>Results: </strong>The Results from phase 1 showed increased activity in both (TRP and MPD) treatments. However, the results of phase 2 showed significant decrease in methylphenidate-induced behavioral sensitization by both pretreatment and co-administration with TRP.</p><p><strong>Conclusion: </strong>The present study suggests the potential of tryptophan to decrease the risk of behavioral sensitization induced by methylphenidate.</p>","PeriodicalId":10746,"journal":{"name":"Current clinical pharmacology","volume":"14 2","pages":"125-131"},"PeriodicalIF":3.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36666697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Azithromycin-induced Aphthous Stomatitis: A Case Series.","authors":"Ehsan T Moghadam,&nbsp;Ali Tafazoli","doi":"10.2174/1574884714666190301153040","DOIUrl":"https://doi.org/10.2174/1574884714666190301153040","url":null,"abstract":"<p><strong>Background: </strong>Azithromycin is one of the most popular antibiotics in current clinical practice. This medication generally considered to be safe and well-tolerated in different demographic populations. Like any other drug, azithromycin use is not without risk and adverse effects. In recent years, cardiovascular accidents have been announced as its major and most important side effect. But azithromycin use can be accompanied with less recognized complications which are significantly discomforting. In this article, we presented a neglected adverse effect of azithromycin in medical literature which is aphthous stomatitis.</p><p><strong>Methods: </strong>We detected three cases with this complication in our center during a one-year period. All the accessible clinical data were recorded and PubMed database was explored to assess the relevant literature.</p><p><strong>Results: </strong>The patients had aphthous stomatitis within 24 hours of the first dose which was healed in about 2 to 3 weeks. Naranjo scoring system showed a probable stage for this adverse drug reaction. There was no such a report in our database search process.</p><p><strong>Conclusion: </strong>It could be stated that aphthous stomatitis is an important adverse effect of azithromycin that can affect the patient's quality of life during therapy and in the majority of cases, it can be neglected by healthcare practitioners.</p>","PeriodicalId":10746,"journal":{"name":"Current clinical pharmacology","volume":"14 3","pages":"242-246"},"PeriodicalIF":3.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574884714666190301153040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37018224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review on the Screening Models for the Pharmacological Assessment of Antiulcer Drugs.","authors":"Abhinav P Mishra,&nbsp;Ankit Bajpai,&nbsp;Suresh Chandra","doi":"10.2174/1574884714666190312143846","DOIUrl":"https://doi.org/10.2174/1574884714666190312143846","url":null,"abstract":"<p><strong>Background: </strong>Due to inappropriate diet, smoking, alcohol consumption, regular use of drugs like NSAIDs and sedentary lifestyle, one may feel upper abdominal pain which may be the predictor of the gastrointestinal disorder called Peptic Ulcer. When an imbalance occurs between the defensive factor and aggressive factor of the stomach, ulcer formation in the esophageal lining, stomach, or duodenum takes place. This leads to the formation of small sores that cause pain. Another condition that synergizes the abdominal pain is vomiting materials which look like coffee grounds, blood in the stool, black or tarry stools. This pain may increase after lunch or dinner. This problem persists, that often leads to the gastroenterologist's consultation.</p><p><strong>Objective: </strong>There are many antiulcer screening models present for the determination of antiulcer activity of the drug molecule. The main objective of this study is to find which model is best for the determination of antiulcer activity.</p><p><strong>Methods: </strong>A literature search was conducted on the databases namely Science direct and PubMed with the help of different keywords such as \"Anti-ulcer\", \"In-vitro models\" and \"In-vivo models\". The search was customized by applying the appropriate filters so as to get the most relevant articles to meet the objective of this review article.</p><p><strong>Result: </strong>There are different research and review papers based on the antiulcer screening models for the determination of antiulcer activity of new drug molecules.</p><p><strong>Conclusion: </strong>On the basis of our study, we found some useful models for the antiulcer activity of drugs and suggested that, if we use in-vitro and in-vivo methods together, then we may obtain the most relevant result in our research area.</p>","PeriodicalId":10746,"journal":{"name":"Current clinical pharmacology","volume":"14 3","pages":"175-196"},"PeriodicalIF":3.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574884714666190312143846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37050493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Nrf2/HO-1 and PI3K/Akt Genes in the Hepatoprotective Effect of Cilostazol.","authors":"Marwa Hassan,&nbsp;Mohamad A Ibrahim,&nbsp;Heba M Hafez,&nbsp;Mervat Z Mohamed,&nbsp;Nagwa M Zenhom,&nbsp;Hend M Abd Elghany","doi":"10.2174/1574884713666180903163558","DOIUrl":"https://doi.org/10.2174/1574884713666180903163558","url":null,"abstract":"<p><strong>Background: </strong>Cilostazol, a phosphodiesterase 3 inhibitor (PDE3I), is a platelet aggregation inhibitor and vasodilator that is useful for treating intermittent claudication. Experimental studies have shown that cilostazol has potent anti-inflammatory, anti-oxidant effects effects.</p><p><strong>Objectives: </strong>Although the hepatoprotective effect cilostazol has been studied, the molecular mechanisms of such protection, including: the nuclear factor-erythroid 2-related factor 2 (Nrf2) / hemoxygenase (HO-1) and the phosphoinositide 3-kinase (PI3K) /serine/threonine kinase (Akt) pathways are not fully explored, which is the aim of this study.</p><p><strong>Methods: </strong>To achieve the aim of this study, 35 rats were grouped into: control groups, liver injury group (model- non treated: injected with thioacetamide (TAA), 150 mg/kg, i.p.), and two cilostazoltreated groups (treated with cilostazol 10 and 50 mg/kg, p.o.). The rats were treated for 8 days and injected with TAA on the 7th day of the experiment and sacrificed 48 hours after TAA injection.</p><p><strong>Results: </strong>The model group showed evidence of liver injury as indicated by the elevation of liver enzymes and confirmed by histopathological findings. TAA-induced liver injury was accompanied by down-regulation of the cytoprotective pathways: PI3K/Akt and Nrf2/HO-1 mRNAs. Cilostazol administration ameliorated TAA-induced liver injury, where it caused a significant improvement in the activity of liver enzymes as well as in the histopathological changes. Such an effect was associated with a significant increase in the expression of PI3K/Akt and Nrf2/HO-1 mRNAs as detected by Real-time reverse transcription polymerase chain reaction (RT-PCR).</p><p><strong>Conclusion: </strong>Cilostazol protected rats against TAA hepatotoxicity through up-regulation of PI3K/Akt and Nrf2/HO-1 gene expression.</p>","PeriodicalId":10746,"journal":{"name":"Current clinical pharmacology","volume":"14 1","pages":"61-67"},"PeriodicalIF":3.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574884713666180903163558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36460587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surotomycin (A Novel Cyclic Lipopeptide) vs. Vancomycin for the Treatment of Clostridioides difficile Infection: A Systematic Review and Meta-analysis.","authors":"Aziz Muhammad,&nbsp;Desai Madhav,&nbsp;Fatima Rawish,&nbsp;Thoguluva C Viveksandeep,&nbsp;Eid Albert,&nbsp;Jackson Mollie,&nbsp;Sharma Prateek","doi":"10.2174/1574884714666190328162637","DOIUrl":"https://doi.org/10.2174/1574884714666190328162637","url":null,"abstract":"<p><strong>Background: </strong>Current guidelines recommend the use of vancomycin for the initial treatment of moderate to severe Clostridioides difficile Infection (CDI). Surotomycin, a novel antibiotic, has been utilized for the management of CDI with variable results.</p><p><strong>Methods: </strong>A systematic literature search was performed using the following electronic databases [Medline, Embase, google scholar and Cochrane] for eligible studies. Randomized controlled trials comparing Surotomycin with Vancomycin for the CDI treatment were included. Demographic variables and outcomes (CDI resolution, CDI recurrence, B1/NAP1/027-specific strain treatment, B1/NAP1/027-strain recurrence, death not related to treatment) were analyzed. The primary outcome was clinical cure rate defined as the resolution of CDI at the end of the 10-day drug course.</p><p><strong>Results: </strong>Three RCTs met the inclusion criteria with a total of 1280 patients with CDI who received either surotomycin 250 mg twice daily (642 patients) or vancomycin 125 mg four times daily (638 patients). Clinical cure rates after 10 days of treatment with either surotomycin or vancomycin were not significantly different (pooled OR: 0.89, 95% CI 0.66-1.18, p=0.41). Sustained clinical response at clinical follow-up and the overall recurrence of CDI were also not significantly different between the two groups - pooled OR 1.15 (95% CI 0.89-1.50, p=0.29) and pooled OR 0.74 (95%CI 0.52- 1.04, p=0.08), respectively. With regards to the NAP1/BI/027 strain, patients in the surotomycin group had significantly lower rates of recurrence compared to vancomycin (pooled OR 0.35, 95% CI 0.19-0.63, p<0.01).</p><p><strong>Conclusion: </strong>Surotomycin is non-inferior to vancomycin and offers a promising alternative for the treatment and prevention of C. diff infection.</p>","PeriodicalId":10746,"journal":{"name":"Current clinical pharmacology","volume":"14 3","pages":"166-174"},"PeriodicalIF":3.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574884714666190328162637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37099891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rabbit as an Animal Model for Pharmacokinetics Studies of Enteric Capsule Contains Recombinant Human Keratinocyte Growth Factor Loaded Chitosan Nanoparticles.","authors":"Palanirajan V Kumar,&nbsp;Marwan A Abdelkarim Maki,&nbsp;Yeong S Wei,&nbsp;Lee M Tatt,&nbsp;Manogaran Elumalai,&nbsp;Shiau-Chuen Cheah,&nbsp;Bharathy Raghavan,&nbsp;Abu Bakar Bin A Majeed","doi":"10.2174/1574884714666181120103907","DOIUrl":"10.2174/1574884714666181120103907","url":null,"abstract":"<p><strong>Background: </strong>Recombinant human keratinocyte growth factor (rHuKGF) has gained considerable attention by researchers as epithelial cells proliferating agent. Moreover, intravenous truncated rHuKGF (palifermin) has been approved by Food and Drug Administration (FDA) to treat and prevent chemotherapy-induced oral mucositis and small intestine ulceration. The labile structure and short circulation time of rHuKGF in-vivo are the main obstacles that reduce the oral bioactivity and dosage of such proteins at the target site.</p><p><strong>Objective: </strong>Formulation of methacrylic acid-methyl methacrylate copolymer-coated capsules filled with chitosan nanoparticles loaded with rHuKGF for oral delivery.</p><p><strong>Methods: </strong>We report on chitosan nanoparticles (CNPs) with diameter < 200 nm, prepared by ionic gelation, loaded with rHuKGF and filled in methacrylic acid-methyl methacrylate copolymercoated capsules for oral delivery. The pharmacokinetic parameters were determined based on the serum levels of rHuKGF, following a single intravenous (IV) or oral dosages using a rabbit model. Furthermore, fluorescent microscope imaging was conducted to investigate the cellular uptake of the rhodamine-labelled rHuKGF-loaded nanoparticles. The proliferation effect of the formulation on FHs 74 Int cells was studied as well by MTT assay.</p><p><strong>Results: </strong>The mucoadhesive and absorption enhancement properties of chitosan and the protective effect of methacrylic acid-methyl methacrylate copolymer against rHuKGF release at the stomach, low pH, were combined to promote and ensure rHuKGF intestinal delivery and increase serum levels of rHuKGF. In addition, in-vitro studies revealed the protein bioactivity since rHuKGFloaded CNPs significantly increased the proliferation of FHs 74 Int cells.</p><p><strong>Conclusion: </strong>The study revealed that oral administration of rHuKGF-loaded CNPs in methacrylic acid-methyl methacrylate copolymer-coated capsules is practically alternative to the IV administration since the absolute bioavailability of the orally administered rHuKGF-loaded CNPs, using the rabbit as animal model, was 69%. Fluorescent microscope imaging revealed that rhodaminelabelled rHuKGF-loaded CNPs were taken up by FHs 74 Int cells, after 6 hours' incubation time, followed by increase in the proliferation rate.</p>","PeriodicalId":10746,"journal":{"name":"Current clinical pharmacology","volume":"14 2","pages":"132-140"},"PeriodicalIF":3.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574884714666181120103907","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36689527","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":"Efficacy and Safety of Nilutamide in Patients with Metastatic Prostate Cancer who Underwent Orchiectomy: A Systematic Review and Metaanalysis.","authors":"Muhammed Rashid, K Shamshavali, Manik Chhabra","doi":"10.2174/1574884714666190112151202","DOIUrl":"10.2174/1574884714666190112151202","url":null,"abstract":"Background Prostate cancer is the sixth leading cause of death, among all cancer deaths By 2030, this burden is expected to increase with 1.7 million new cases and 499,000 new deaths. We aimed to evaluate the efficacy and safety of Nilutamide in metastatic prostate cancer (mPCa) patients who underwent orchiectomy. Methods A comprehensive search was conducted in the Medline/PubMed and Cochrane Library. References from included studies and studies from clinicaltrials.gov were explored without language and date restrictions. We included only randomized controlled trials, comparing the safety and efficacy of Nilutamide in Metastatic Prostate Cancer (mPCa) patients who underwent orchiectomy with placebo. The outcomes of concerns were survival and the response of drug and safety.. Quality of the included studies was assessed using the Cochrane Risk of Bias Tool. Two authors were independently involved in the study selection, data extraction and quality assessment. Disagreements between the two reviewers were resolved by consulting a third reviewer. Results A total of five out of 244 studies were included in meta-analysis involving1637 participants. Nilutamide group showed improved response rate (RR=1.77, 95%CI 1.46-2.14, p<0.00001), disease progression (RR=0.59, 95%CI 0.47-0.73, p<0.00001), complete response (RR=2.13, 95%CI 1.40-3.23, p=0.003) and clinical benefit (RR=1.23, 95%CI 1.13-1.34, p<0.00001) when compared to placebo; however, stable disease favored the control group (RR=0.80, 95%CI 0.68-0.94, p=0.007). In addition, patients on Nilutamide showed prolonged progression-free survival and overall survival. Nausea and vomiting were the most common adverse events reported in Nilutamide group. Conclusion Evidence suggests that patients with mPCa who underwent orchiectomy receiving Nilutamide showed significant improvement in progression-free survival and overall survival response rate and clinical benefits in comparison with the placebo group.","PeriodicalId":10746,"journal":{"name":"Current clinical pharmacology","volume":"14 2","pages":"108-115"},"PeriodicalIF":3.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574884714666190112151202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36857554","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":"The Cytotoxicity and Synergistic Potential of Aspirin and Aspirin Analogues Towards Oesophageal and Colorectal Cancer.","authors":"Rajagopal S Kilari,&nbsp;Asma'u I J Bashir,&nbsp;Andreue Devitt,&nbsp;Christopher J Perry,&nbsp;Stephen T Safrany,&nbsp;Iain D Nicholl","doi":"10.2174/1574884713666181112141151","DOIUrl":"https://doi.org/10.2174/1574884713666181112141151","url":null,"abstract":"<p><strong>Background: </strong>Oesophageal cancer (OC) is a deadly cancer because of its aggressive nature with survival rates that have barely improved in decades. Epidemiologic studies have shown that low-dose daily intake of aspirin can decrease the incidence of OC.</p><p><strong>Methods: </strong>The toxicity of aspirin and aspirin derivatives to OC and a CRC cell line were investigated in the presence and absence of platins.</p><p><strong>Results: </strong>The data in this study show the effects of a number of aspirin analogues and aspirin on OC cell lines that originally presented as squamous cell carcinoma (SSC) and adenocarcinoma (ADC). The aspirin analogues fumaryldiaspirin (PN517) and the benzoylsalicylates (PN524, PN528 and PN529), were observed to be more toxic against the OC cell lines than aspirin. Both quantitative and qualitative apoptosis experiments reveal that these compounds largely induce apoptosis, although some necrosis was evident with PN528 and PN529. Failure to recover following the treatment with these analogues emphasized that these drugs are largely cytotoxic in nature. The OE21 (SSC) and OE33 (ADC) cell lines were more sensitive to the aspirin analogues compared to the Flo-1 cell line (ADC). A non-cancerous oesophageal primary cells NOK2101, was used to determine the specificity of the aspirin analogues and cytotoxicity assays revealed that analogues PN528 and PN529 were selectively toxic to cancer cell lines, whereas PN508, PN517 and PN524 also induced cell death in NOK2101. In combination index testing synergistic interactions of the most promising compounds, including aspirin, with cisplatin, oxaliplatin and carboplatin against the OE33 cell line and the SW480 colorectal cancer (CRC) cell line were investigated. Compounds PN517 and PN524, and to a lesser extent PN528, synergised with cisplatin against OE33 cells. Cisplatin and oxaliplatin synergised with aspirin and PN517 when tested against the SW480 cell line.</p><p><strong>Conclusion: </strong>These findings indicate the potential and limitations of aspirin and aspirin analogues as chemotherapeutic agents against OC and CRC when combined with platins.</p>","PeriodicalId":10746,"journal":{"name":"Current clinical pharmacology","volume":"14 2","pages":"141-151"},"PeriodicalIF":3.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1574884713666181112141151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36666699","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}