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A CXCR3-Activating Peptide Increases Tear Break Up Time and Corrects Corneal haze in a Rabbit Model of Environmental Dry Eye. 一种 CXCR3 激活肽能延长泪液破裂时间并矫正环境性干眼症兔模型中的角膜混浊。
Pub Date : 2024-01-01 Epub Date: 2024-04-17 DOI: 10.26502/fjppr.094
Alan Wells, Yadong Wang, Hanshuang Shao, Peri Sohnen, Shivalingappa K Swamynathan

Purpose: Environmentally-triggered dry eye disease (DED) or keratoconjunctivitis sicca (KCS), which constitutes the majority of DED cases, currently is palliatively treated with aqueous replacement solutions that do not target the dysfunction of the mucin and lipid components of tears. We tested whether a peptide that increased goblet cell numbers in a model of scleral chemical injury would also improve tear quality in environmental DED.

Methods: Environmental DED was established by exposing New Zealand white rabbits (8 per group, female) to 20% humidity with rapid air replacement and b.i.d. atropine sulfate eyedrops for 3 weeks prior to test article administration; this continued for the subsequent 3 weeks of testing. Animals were dosed by (A) saline, (B) b.i.d. eyedrop of peptide in saline, (C) b.i.d. eyedrop of peptide in coacervate, or (D) weekly subconjunctival injection of peptide. In vitro, human conjunctival epithelial cells (HCjE) were exposed to TNFα in the presence or absence of peptide to determine inflammatory responsiveness.

Results: The environmental DED was established with both Schirmer and TBUT being reduced at the start of test article; these levels were maintained as low through the testing period. All three treatment regimens increased TBUT approximately 3x to levels greater than prior to desiccation (P < 0.01), with little effect on Schirmer. Corneal haze was present in all eyes after induction, and completely reversed in 36 of 48 eyes across the treatments (P < 0.05). Co-treatment of HCjE with peptide reduced the production of TNFα in response to an inflammatory stimulus.

Conclusions: The treatment of environmental DED/KCS with a peptide that activates CXCR3 improved tear quality and reversed corneal pathology by promoting tear stability and likely dampening the corneal inflammation, while not affecting aqueous volume of the tears.

目的:环境诱发的干眼症(DED)或角结膜炎(KCS)占 DED 病例的大多数,目前只能通过水替代溶液进行缓解性治疗,而这些溶液并不针对泪液中粘蛋白和脂质成分的功能障碍。我们测试了一种能在巩膜化学损伤模型中增加泪腺细胞数量的肽是否也能改善环境性 DED 的泪液质量:环境性 DED 是通过将新西兰白兔(每组 8 只,雌性)暴露在湿度为 20% 的环境中,并快速更换空气,同时在给药前 3 周内滴注硫酸阿托品眼药水;在随后的 3 周测试中继续这样做。动物的用药方式为:(A) 生理盐水;(B) 生理盐水中的肽滴眼液;(C) 玻尿酸中的肽滴眼液;或 (D) 每周结膜下注射一次肽。在体外,人结膜上皮细胞(HCjE)暴露于有或没有多肽的 TNFα 下,以确定炎症反应性:环境 DED 试验开始时,Schirmer 和 TBUT 均有所下降;在试验期间,这些水平一直保持在较低水平。所有三种治疗方案都将 TBUT 提高了约 3 倍,达到了干燥前的水平(P < 0.01),但对 Schirmer 的影响很小。所有眼睛在诱导后都出现了角膜混浊,在 48 只眼睛中,有 36 只眼睛的角膜混浊在不同的治疗方案中完全逆转(P < 0.05)。用多肽联合治疗 HCjE 可减少 TNFα 在炎症刺激下的产生:结论:用一种能激活 CXCR3 的多肽治疗环境性 DED/KCS 可改善泪液质量并逆转角膜病理,因为它能促进泪液稳定性并可能抑制角膜炎症,同时不影响泪液的水容量。
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引用次数: 0
Trends in Antimicrobial Resistance in Gaza Strip, 2020–2022: Retrospective Study 2020-2022年加沙地带抗菌素耐药性趋势:回顾性研究
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.076
Hashem M. Mansour, Rana A. Kurraz, Ahmed Al Rabii, Khalil I. Masood
Objectives: In this study, we analyzed the data on antimicrobial resistance in the bloodstream . This study aims to evaluate the bacterial resistance in the Gaza Strip and compare with that in other countries. Methods: This study was conducted retrospectively in the Indonesian and Shifa hospitals in the Gaza Strip of Palestine. The isolates were collected from 2020 to 2022 and compared with those from other countries. Chi square test to compare between means. P-value less than 0.05 was considered statistically significant. Results: The incidences of bloodstream infections as well as the resistance against most antibiotics increased. The exceptions were a decreased incidence of P. aeruginosa infection and a decrease in resistance against ceftazidime. Overall, the incidence and resistance of antimicrobials were higher than other countries. Conclusion: These results showed increased trends to bacterial resistance except for ceftazidime. A specialist in clinical microbiology should take an active role in prescribing antibiotics in hospitals based on laboratory and epidemiological data besides clinical experience. Also, antibiotic stewardship should be constructed and activated in our country to, as this will decrease the emergence of resistant strains and decrease the burden
目的:在本研究中,我们分析了血液中抗菌素耐药性的数据。本研究旨在评估加沙地带的细菌耐药性,并与其他国家进行比较。方法:回顾性分析巴勒斯坦加沙地带印尼医院和希法医院的临床资料。这些分离株收集于2020 - 2022年,并与来自其他国家的分离株进行比较。用卡方检验比较均数。p值小于0.05认为有统计学意义。结果:血源性感染发生率增高,多数抗生素耐药性增高。例外情况是铜绿假单胞菌感染发生率下降,对头孢他啶的耐药性下降。总体而言,抗菌药物的发病率和耐药性高于其他国家。结论:除头孢他啶外,其余细菌耐药呈上升趋势。临床微生物学专家除了临床经验外,还应根据实验室和流行病学资料积极参与医院的抗生素处方工作。此外,应在我国建立和激活抗生素管理,因为这将减少耐药菌株的出现并减轻负担
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引用次数: 0
High Dose of Metformin Decreases Susceptibility to Occlusive Arterial Thrombosis in Diabetic Mice. 大剂量二甲双胍降低糖尿病小鼠闭塞性动脉血栓形成的易感性。
Pub Date : 2023-01-01 Epub Date: 2023-10-16
Roberto I Mota Alvidrez, Gowtham K Annarapu, Amudan J Srinivasan, Zeyu Liu, Hamza O Yazdani, Deidre Nolfi-Donegan, Richard L Simmons, Sruti Shiva, Matthew D Neal

Introduction: Metformin is the most prescribed medication in Diabetes Mellitus(DM). Metformin has shown to decrease mean platelet volume, with promising antiplatelet effects. High doses of Metformin have also been associated with hypercoagulation. We hypothesize that Metformin will protect DM mice from occlusive arterial thrombus formation by altering platelet activation and mitochondrial bioenergetics.

Methods: DM was developed by low dose of Streptozotocin, non-DM (healthy) mice are controls. Either vehicle or Metformin was administered twice daily via oral gavage for 7-days. Ferric chloride (FeCl3) arterial thrombosis and tail bleeding time were performed. Whole blood aggregometry, platelet activation/adhesion and mitochondrial bioenergetics were evaluated.

Results: Metformin decreased susceptibility of DM mice to arterial thrombosis. Platelet bioenergetics show DM mice have increased platelet mitochondrial respiration, but no differences were observed with Metformin treatment. In non-DM (healthy) mice, Metformin modulated ADP-dependent increase in platelet adhesion. Non-DM (healthy) mice, Metformin shortens bleeding time with faster thrombotic occlusion. Metformin also increased platelet mitochondrial maximal respiration and spare respiratory capacity uniquely in non-DM (healthy) mice.

Conclusion: Metformin regulates platelet bioenergetics and ADP-mediated platelet function in DM mice which attenuates susceptibility to arterial thrombosis. Future studies will evaluate clinically relevant doses of Metformin that regulates thrombotic function in diabetic platelets.

简介:二甲双胍是糖尿病(DM)最常用的处方药。二甲双胍已显示降低平均血小板体积,具有良好的抗血小板作用。高剂量的二甲双胍也与高凝有关。我们假设二甲双胍会通过改变血小板激活和线粒体生物能量学来保护糖尿病小鼠免于闭塞性动脉血栓形成。方法:采用低剂量链脲佐菌素诱导DM,以非DM(健康)小鼠为对照。给药组或二甲双胍组每天2次灌胃,连续7天。观察三氯化铁(FeCl3)动脉血栓形成及尾出血时间。评估全血聚集、血小板活化/粘附和线粒体生物能量学。结果:二甲双胍可降低糖尿病小鼠动脉血栓形成的易感性。血小板生物能量学显示糖尿病小鼠血小板线粒体呼吸增加,但二甲双胍治疗组无差异。在非糖尿病(健康)小鼠中,二甲双胍调节adp依赖性血小板粘附增加。非糖尿病(健康)小鼠,二甲双胍缩短出血时间和更快的血栓闭塞。二甲双胍还增加了非糖尿病(健康)小鼠血小板线粒体最大呼吸量和备用呼吸量。结论:二甲双胍调节糖尿病小鼠血小板生物能量和adp介导的血小板功能,减轻动脉血栓形成的易感性。未来的研究将评估临床上相关剂量的二甲双胍调节糖尿病血小板的血栓形成功能。
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引用次数: 0
Antidiabetic Potential of The Leaf Extracts of Phragmanthera incana (Schum.) Balle Harvested on Albizia lebbeck 金菖蒲叶提取物的抗糖尿病作用研究产自白百合
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.069
E. Bamgbade, Samson Oluwaseyi Famuyiwa, K. Faloye, Marcus Durojaye Ayoola, Charlotte Mungho Tata, Marthe Carine Djuidje FOTSING, D. Ndinteh
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引用次数: 0
COVID-19 Home Therapy. It Has Never Been a Matter of Freedom of Cure COVID-19家庭治疗。这从来都不是自由治疗的问题
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.081
Salvatore Chirumbolo, Luigi Valdenassi, Marianno Franzini
I read carefully the recent paper by Fazio et al., on this journal, where the authors widely criticized the approach with which COVID-19 pandemic was addressed by the Italian Government in the dramatic period 2020-2022 [1]. They focused all major concerns on the failure in recommending a sound and reliable home COVID-19 therapy, an issue particularly debated on my own [2-5]. The authors detailed with commendable stubbornness the many shortcomings (and mistakes, as they stated) of the Italian Government Institutions engaged to address public health policy during the COVID-19 pandemic emergency, some of these allegations were addressed also elsewhere [6]. Yet, I wrote this Letter to the Editor because, despite I retrieved some scientific convergence in the tale exposed by the colleagues, I would like to raise doubts about the “alternative” the authors make available as a convenient proposal, i.e., “freedom of cure” rather than “Government guidelines”. First, naming as a “Government’s guideline” a draft focused on a trivial, commonly used painkiller to address SARS-CoV2 infection at the earliest, is ridiculous.
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引用次数: 0
Therapeutic Drug Monitoring of Pregabalin in a Critically ill Patient with Acute Kidney Injury undergoing Continuous, Prolonged Intermittent, and Intermittent Kidney Replacement Therapy 普瑞巴林在急性肾损伤的危重患者接受持续、长时间间歇和间歇肾替代治疗中的治疗药物监测
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.086
Francesca Di Mario, Eleonora Galosi, Paolo Greco, Caterina Maccari, Brenda Menegazzo, Teresa Coccini, Elisa Roda, Enrico Fiaccadori
Pregabalin is an anti-epileptic drug which also represents one of the most frequently prescribed medications for neuropathic pain management worldwide. Moreover, in recent years its use has widely increased also in critically ill patients in the setting of multimodal analgesia. Commonly available as capsules and oral solution, it is characterized by a predominant kidney elimination. Consequently, in patients with kidney failure posology adjustments are needed. According to the pharmacokinetic parameters (low molecular weight and volume of distribution, negligible protein binding), pregabalin is expected to undergo a significant extracorporeal clearance, which should be taken into account when one of the different Kidney Replacement Therapy (KRT) modalities is required for Acute Kidney Injury (AKI). The case of a critically ill patient with AKI undergoing Therapeutic Drug Monitoring of Pregabalin in course of Continuous, Prolonged Intermittent KRT (CKRT and PIKRT, respectively), and conventional intermittent hemodialysis (IHD) is presented here for the first time.
普瑞巴林是一种抗癫痫药物,也是世界上最常用的神经性疼痛治疗药物之一。此外,近年来,在多模式镇痛的情况下,它的使用也在危重患者中广泛增加。通常作为胶囊和口服溶液,它的特点是主要的肾脏消除。因此,在肾衰竭患者中,需要进行病理调整。根据药代动力学参数(低分子量和分布体积,可忽略的蛋白质结合),普瑞巴林有望经历显著的体外清除,当急性肾损伤(AKI)需要不同肾脏替代治疗(KRT)方式之一时,应考虑到这一点。本文首次报道了一例重症AKI患者在连续、延长间歇KRT(分别为CKRT和PIKRT)和常规间歇血液透析(IHD)过程中接受普瑞巴林治疗药物监测的病例。
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引用次数: 0
Correction of Over-Dosed Insulin in a Type-2- Diabetic Led to a Better Control of Glycemia and Arterial Hypertension: A Case Report 纠正2型糖尿病患者过量胰岛素可更好地控制血糖和动脉高血压1例
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.087
Abimbola Abobarin-Adeagbo, Torsten Kraya, Matthias Girndt, Rainer Ullrich Pliquett
Introduction: An association between hypoglycemia and arterial hypertension has been proposed. Here, we report a case of an elderly type-2 diabetic presenting with hypertensive crisis, which improved after insulin-dose reduction.
导读:低血糖和动脉高血压之间存在关联。在这里,我们报告一例老年2型糖尿病患者出现高血压危象,在胰岛素剂量减少后好转。
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引用次数: 0
Modulatory Effect of Sodium Butyrate on the Anticancer Activity of Abemaciclib in MDA-MB-231 Human Breast Cancer Cells 丁酸钠对Abemaciclib对MDA-MB-231人乳腺癌细胞抗癌活性的调节作用
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.071
Neveen A. Elnozahi, Esraa A. Abdelaziz, Maged W. Helmy, Azza E. Bistawroos
Triple negative breast cancer is the most aggressive subtype of breast cancer, and its treatment is limited. The effect of abemaciclib and /or sodium butyrate on MDA-MB-231 triple negative breast cancer cells was investigated. The IC50 for the growth inhibitory effects of abemaciclib, sodium butyrate, and their combination were 14.55 μM, 7.08 mM, and 3.743 mM, respectively. The combination showed a synergistic interaction with a decrease in IC50 to 2.55 μM abemaciclib and 3.74 mM butyrate. Three replicates of four groups of cancer cells were treated for 48 hr with the IC50 of abemaciclib, butyrate or their high or low dose combinations. A fifth group was treated with complete medium and served as the control. Cell migration, protein expression levels of cyclin D1, E2F2 transcription factor, phosphorylated AKT, nuclear factor kappa B (NF-κB), cyclin dependent kinase-2 (CDK2), retinoblastoma (Rb), p16INK4a, p53 and mRNA levels of CDK2, p16INK4a and p53 were assessed in all treated groups. Combination treatment with abemaciclib and butyrate showed a significant attenuation of cell metastasis. The combination treatment was associated with a decrease in E2F2, CDK2, and NF-κB protein levels together with attenuation in AKT phosphorylation level. The combination also showed an elevation in Rb, and p16INK4a, together with a reversal of DNA hypo-methylated state. Although abemaciclib monotherapy failed to alter cyclin D1 or p53 levels, the combination significantly reduced cyclin D1 level together with an increase in P53 level. In conclusion, combining butyrate with abemaciclib augmented its antiproliferative and antimetastatic effects and induced apoptotic activity
三阴性乳腺癌是最具侵袭性的乳腺癌亚型,其治疗是有限的。研究了阿贝马昔利布和/或丁酸钠对MDA-MB-231三阴性乳腺癌细胞的影响。abemaciclib、丁酸钠及其联合用药的IC50分别为14.55 μM、7.08 mM和3.743 mM。该组合显示出协同相互作用,IC50降至2.55 μM abemaciclib和3.74 mM丁酸盐。用阿贝马昔利、丁酸盐或其高、低剂量组合治疗4组癌细胞,3个重复,治疗48小时。第五组用完全培养基处理,作为对照组。观察各组细胞迁移、细胞周期蛋白D1、E2F2转录因子、磷酸化AKT、核因子κB (NF-κB)、细胞周期蛋白依赖性激酶2 (CDK2)、视网膜母细胞瘤(Rb)、p16INK4a、p53蛋白表达水平及CDK2、p16INK4a、p53 mRNA表达水平。阿贝马昔单抗与丁酸盐联合治疗能显著抑制细胞转移。联合治疗与E2F2、CDK2和NF-κB蛋白水平降低以及AKT磷酸化水平降低相关。该组合还显示Rb和p16INK4a的升高,以及DNA低甲基化状态的逆转。尽管abemaciclib单药治疗未能改变cyclin D1或p53水平,但联合治疗可显著降低cyclin D1水平并增加p53水平。综上所述,丁酸盐与阿贝马昔利布联合使用增强了其抗增殖和抗转移作用,并诱导了细胞凋亡活性
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引用次数: 1
Impact of Early Palliative Care on End of life in patients with Advanced Biliary Tract Cancer 早期姑息治疗对晚期胆道癌患者生命终结的影响
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.065
M. Miralles, Marie Muller, C. Borg, S. Manfredi
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引用次数: 0
A Systems Pharmacology Approach, Using Molecular Docking and Dynamics Simulation, to Unlock Potential New Therapies for Alzheimer’s Disease: A Case Study of Cinnamon Species 系统药理学方法,利用分子对接和动力学模拟,解锁阿尔茨海默病的潜在新疗法:肉桂物种的案例研究
Pub Date : 2023-01-01 DOI: 10.26502/fjppr.074
W. Qiu, Shouli Yuan, Robbie Kelleher, Lina Sun, Wei Chen, H. Sheridan, Junying Liu, W. Lv
{"title":"A Systems Pharmacology Approach, Using Molecular Docking and Dynamics Simulation, to Unlock Potential New Therapies for Alzheimer’s Disease: A Case Study of Cinnamon Species","authors":"W. Qiu, Shouli Yuan, Robbie Kelleher, Lina Sun, Wei Chen, H. Sheridan, Junying Liu, W. Lv","doi":"10.26502/fjppr.074","DOIUrl":"https://doi.org/10.26502/fjppr.074","url":null,"abstract":"","PeriodicalId":73897,"journal":{"name":"Journal of pharmacy and pharmacology research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69347884","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}
引用次数: 0
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Journal of pharmacy and pharmacology research
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