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Drug Design, Development and Therapy

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https://www.readbyqxmd.com/read/30013326/safety-and-efficacy-of-durvalumab-medi4736-in-various-solid-tumors
#1
Hui Yang, Kai Shen, Chenjing Zhu, Qingfang Li, Yunuo Zhao, Xuelei Ma
Introduction: The prominent immune checkpoint molecule, programmed cell death ligand-1 (PD-L1), is the object of increasing attention. Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors. Methods: A systematic search of PubMed, Embase, and related articles was performed. Safety data were analyzed using Comprehensive Meta-Analysis software program version 2. Ultimately, 17 studies with 1,529 patients were included in our analysis...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/30013325/different-doses-of-tenecteplase-vs-alteplase-in-thrombolysis-therapy-of-acute-ischemic-stroke-evidence-from-randomized-controlled-trials
#2
Na Xu, Zhouqing Chen, Chongshun Zhao, Tao Xue, Xin Wu, Xiaoou Sun, Zhong Wang
Background: Recent studies showed inconsistent results of tenecteplase vs alteplase for acute ischemic stroke (AIS) with safety and efficacy. Methods: A meta-analysis was performed to explore the value of tenecteplase and alteplase in AIS treatment. Medline, Embase, and Cochrane Library from January 2001 to April 2018 were searched for randomized controlled trials (RCTs) with tenecteplase vs alteplase for AIS. Results: The primary outcomes were early neurological improvement at 24 h and functional outcome at 3 months...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/30013324/self-nanomicellizing-solid-dispersion-of-edaravone-part-i-oral-bioavailability-improvement
#3
Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou
Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut® , intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/30013323/effect-of-preoperative-loading-dose-ticagrelor-and-clopidogrel-on-no-reflow-phenomenon-during-intervention-in-patients-with-st-segment-elevation-myocardial-infarction-undergoing-primary-percutaneous-coronary-intervention-a-systematic-review-and-meta-analysis
#4
Weiran Dai, Ziliang Ye, Lang Li, Qiang Su
Background: Previous studies have shown that ticagrelor is more effective than clopidogrel in platelet inhibition. However, this conclusion remains controversial. Therefore, we performed this meta-analysis to assess the effect of preoperative loading dose ticagrelor and clopidogrel on no-reflow (NRF) during intervention in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI). Materials and methods: Randomized controlled trials and observational studies were reviewed...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/30013322/comparisons-of-therapeutic-efficacy-and-safety-of-ipilimumab-plus-gm-csf-versus-ipilimumab-alone-in-patients-with-cancer-a-meta-analysis-of-outcomes
#5
Peng Chen, Fuchao Chen, Benhong Zhou
Background: Recent clinical studies have shown that initial therapy with combined cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade and granulocyte-macrophage colony-stimulating factor (GM-CSF)-based immunotherapies can enhance the antitumor efficacy of this approach. A key unanswered question is whether systemic GM-CSF enhances CTLA-4 blockade. Thus, the objective of this study was taking a meta-analysis of randomized controlled trials to compare the effect of ipilimumab plus GM-CSF versus ipilimumab alone on overall response, overall survival, and progression-free survival, as well as the risk of adverse events (AEs) in patients with cancer...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/30013321/comparison-of-nocturnal-symptoms-in-advanced-parkinson-s-disease-patients-with-sleep-disturbances-pramipexole-sustained-release-versus-immediate-release-formulations
#6
Wei Xiang, Ya Qing Sun, Hui Chin Teoh
Background: Nocturnal symptoms are common in Parkinson's disease (PD), which greatly affect the quality of life but are often overlooked in clinical settings. Treatment strategies that provide sustained dopaminergic stimulation may have sleep benefits. Objective: To investigate the treatment effects of pramipexole (PPX) sustained release (SR) versus PPX immediate release (IR) on nocturnal symptoms in advanced PD patients with sleep disturbances. Materials and methods: In this study, the PPX clinical trial (NCT00466167) was retrospectively analyzed for PD Sleep Scale (PDSS) total and domain scores in patients with advanced idiopathic PD receiving either PPX SR or PPX IR, who experienced motor fluctuations while on stable levodopa with a baseline PDSS total score of <90, indicating sleep disturbances...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/30013320/efficacy-and-safety-of-adalimumab-in-the-treatment-of-non-infectious-uveitis-a-meta-analysis-and-systematic-review
#7
REVIEW
Shuai Ming, Kunpeng Xie, Huijuan He, Ya Li, Bo Lei
Objective: To summarize updated evidences on the efficacy and safety of adalimumab (ADA) in the treatment of patients with non-infectious uveitis. Patients and methods: A systematic search between January 2000 and September 2017 was conducted using PubMed, Embase, and Cochrane libraries. We investigated control of inflammation, improvement of visual acuity (VA), corticosteroid-sparing effect, and adverse events (AEs) or serious adverse events. Results: Three randomized clinical trials (RCTs) and 20 non-RCTs were included and analyzed...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/30013319/the-possibility-of-healing-alveolar-bone-defects-with-simvastatin-thermosensitive-gel-in-vitro-in-vivo-evaluation
#8
Hong Ruan, Youcheng Yu, Xuehua Guo, Qian Jiang, Ying Luo
Background: In this study, simvastatin (SVT) in situ gels were successfully produced by our group. Methods: The preparations were characterized in the following aspects: in vitro gelation, drug release, stability and pharmacodynamics. Results: In this study, drug content of prepared gels was found to be in the range between 89 and 92%. The pH value was in the range between 6.5 and 7.0. The gelation temperature of the prepared thermogelling solutions was 37°C...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/30013318/antiangiogenic-cytokines-as-potential-new-therapeutic-targets-for-resveratrol-in-diabetic-retinopathy
#9
REVIEW
Mihaela Popescu, Cătălina Bogdan, Adela Pintea, Dumitriţa Rugină, Corina Ionescu
Diabetes mellitus (DM) affects >350 million people worldwide. With many complications that can reduce the patient's quality of life, vision loss is one of the most debilitating disorders it can cause. Active research in the field of diabetes includes microvascular complications in diabetic retinopathy (DR). Disturbances in the balance of pro-angiogenesis and anti-angiogenesis factors can lead to the progression of DR. The retinal pigment epithelium (RPE) is the outermost layer of the retina, and it is essential in maintaining the visual function...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/30013317/pharmacokinetics-of-placental-protein-13-after-intravenous-and-subcutaneous-administration-in-rabbits
#10
Tijana Drobnjak, Hamutal Meiri, Maurizio Mandalá, Berthold Huppertz, Sveinbjörn Gizurarson
Introduction: Human placental protein 13 (PP13) is a galectin predominantly expressed by the placenta. Low serum concentrations of PP13 in early pregnancy indicate a higher risk of developing preeclampsia. Methods: The pharmacokinetic disposition and bioavailability of PP13 were determined by single intravenous and subcutaneous administration to 12 healthy New Zealand White rabbits. The serum pharmacokinetic values were determined by enzyme-linked immunosorbent assay, and are best described by a two-compartment model...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29997433/gemcitabine-hydrochloride-microspheres-used-for-intravesical-treatment-of-superficial-bladder-cancer-a-comprehensive-in-vitro-ex-vivo-in-vivo-evaluation
#11
Sinem Yaprak Karavana, Zeynep Ay Şenyiğit, Çağrı Çalışkan, Gülnur Sevin, Derya İlem Özdemir, Yalçın Erzurumlu, Sait Şen, Esra Baloğlu
Introduction: Bladder cancer is responsible for more than 130,000 deaths annually worldwide. Intravesical delivery of chemotherapeutic agents provides effective drug localization to the target area to reduce toxicity and increase efficacy. This study aimed to develop an intravesical delivery system of gemcitabine HCl (Gem-HCl) to provide a sustained-release profile, to prolong residence time, and to enhance its efficiency in the treatment of bladder cancer. Materials and methods: For this purpose, bioadhesive microspheres were successfully prepared with average particle size, encapsulation efficiency, and loading capacity of 98...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29988771/daptomycin-a-comparison-of-two-intravenous-formulations
#12
REVIEW
Celeste Frankenfeld, Sachin Mittal, Yanira Melendez, Luke Mendez-Vigo, Kenneth C Lamp, Kaitlin N Keller, Shellie R Bertolami
Daptomycin is a cyclic lipopeptide antibacterial agent with potent bactericidal activity against a broad range of Gram-positive organisms. In 2003, daptomycin for injection received approval from the US Food and Drug Administration (FDA) for the treatment of patients with complicated skin and skin structure infections (cSSSIs); in 2006, it was approved for the treatment of patients with Staphylococcus aureus bacteremia, including those with right-sided infective endocarditis caused by methicillin-susceptible and methicillin-resistant isolates...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29983548/mechanism-of-yanghe-pingchuan-granules-treatment-for-airway-remodeling-in-asthma
#13
Ling Yu Pan, Yan Quan Han, Yong Zhong Wang, Qian Qian Chen, Ying Wu, Yuan Sun
Purpose: Yanghe Pingchuan granules (YPG), a hospital preparation developed by The First Affiliated Hospital, Anhui University of Chinese Medicine, has been used for the clinical treatment of bronchial asthma (BA) for several decades. This study aimed to explore the mechanism of action of YPG in the treatment of BA. Materials and methods: Male Sprague Dawley rats (n=60) were randomly divided into six groups (n=10 per group): control, a BA model, positive drug control (Guilong Kechuanning capsules; a proven effective treatment for BA), and model rats treated with a high, medium, or low dose of YPG...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29983547/computer-aided-drug-design-and-inhibitive-effect-of-a-novel-nitrogenous-heterocyclic-compound-and-its-mechanism-on-glioma-u251-cells-and-breast-cancer-mcf-7-cells
#14
Liyu Qian, Yu Zhu
Background: Glioma and breast cancer are severe malignant cancerous tumors that highlight the importance of developing new anti-cancer drugs. The aim of this study was to explore the effects of a novel nitrogenous heterocyclic compound on glioma and breast cancer cells and to determine its mechanism of action. Methods: We designed and synthesized a novel nitrogenous heterocyclic compound, 3-(4-amino-1H-benzo[d]imidazole-2-carboxamido)-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5] tetrazine-8-carboxamide, based on alkylglycerone phosphate synthase (AGPS) using computer-aided drug design (CADD), and we measured its effect on the proliferation, invasion, cell cycle and apoptosis of U251 glioma and MCF-7 breast cancer cells...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29983546/electroporation-enhanced-transdermal-diclofenac-sodium-delivery-into-the-knee-joint-in-a-rat-model-of-acute-arthritis
#15
Petra Hartmann, Edina Butt, Ágnes Fehér, Ágnes Lilla Szilágyi, Kurszán Dávid Jász, Boglárka Balázs, Mónika Bakonyi, Szilvia Berkó, Gábor Erős, Mihály Boros, Gyöngyi Horváth, Endre Varga, Erzsébet Csányi
Purpose: Since electroporation (EP) can increase the permeability of biological membranes, we hypothesized that it offers an opportunity to enhance the transdermal delivery of drugs for intra-articular indications. Our aim was to compare the anti-inflammatory and analgesic efficacy of EP-combined topical administration of diclofenac sodium hydrogel (50 mg mL-1 in 230 µL volume) with that of an equivalent dose of oral (75 mg kg-1 ) and simple topical administration. Methods: Arthritis was induced with the injection of 2% λ-carrageenan and 4% kaolin into the right knee joints of male Sprague Dawley rats...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29983545/the-mechanism-of-botulinum-a-on-raynaud-syndrome
#16
Yanwen Zhou, Ying Liu, Yunhua Hao, Ya Feng, Lizhen Pan, Wuchao Liu, Bing Li, Libin Xiao, Lingjing Jin, Zhiyu Nie
Background: Botulinum neurotoxin type A (BoNT/A) is emerging as a treatment modality for Raynaud's phenomenon (RP). However, the mechanism of the role of BoNT/A in antagonizing the constriction of arteriola in RP remains unclear. Materials and methods: We tested the constriction of arteriole diameter and the distribution of adrenergic receptors on the rat cremaster modle. Moreover, we measured the secretion of norepinephrine (NE), protein level changes and related receptors on cultured rat superior cervical ganglia neurons(SCGNs), a model of sympathetic neuron...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29983544/modes-of-cell-death-induced-by-tetrahydroisoquinoline-based-analogs-in-mda-mb-231-breast-and-a549-lung-cancer-cell-lines
#17
Marcel Nel, Anna M Joubert, Wolfgang Dohle, Barry Vl Potter, Anne E Theron
Background: A and B rings of the steroidal microtubule disruptor, 2-methoxyestradiol, and its analogs can be mimicked with a tetrahydroisoquinoline (THIQ) core. THIQs are cytotoxic agents with potential anticancer activities. The aim of this in vitro study was to investigate the modes of cell death induced by four nonsteroidal THIQ-based analogs, such as STX 2895, STX 3329, STX 3451 and STX 3450, on MDA-MB-231 metastatic breast and A549 epithelial lung carcinoma cells. Materials and methods: Cytotoxicity studies determined the half-maximal growth inhibitory concentration of the analogs to be at nanomolar concentrations without the induction of necrosis...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29983543/senkyunolide-a-protects-neural-cells-against-corticosterone-induced-apoptosis-by-modulating-protein-phosphatase-2a-and-%C3%AE-synuclein-signaling
#18
Shenglan Gong, Jin Zhang, Zhouke Guo, Wenjun Fu
Background: Depression is characterized by a pathological injury to the hippocampal neurons. Senkyunolide A (SenA) is one of the major active components of Dan-zhi-xiao-yao-san, which is widely used in the treatment of depression-related disorders. Materials and methods: In the present study, it was hypothesized that the antidepressant effect of Dan-zhi-xiao-yao-san depended on the function of SenA and the authors attempted to reveal the molecular mechanism associated with the treatment...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29970959/additive-effect-of-oral-ldd175-to-tamsulosin-and-finasteride-in-a-benign-prostate-hyperplasia-rat-model
#19
Bo Ram Choi, Hye Kyung Kim, Kiran Kumar Soni, Keshab Kumar Karna, Sung Won Lee, Insuk So, Jong Kwan Park
Objective: We investigated the benefits of the BKCa agonist 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (LDD175) combined with tamsulosin and finasteride, in a benign prostatic hyperplasia (BPH) rat model. Materials and methods: Castration was performed by bilateral orchiectomy under ketamine anesthesia. A rat model of BPH was established by daily intramuscular administration of testosterone propionate plus 17β-estradiol for 8 weeks...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29970958/salidroside-ameliorates-autophagy-and-activation-of-hepatic-stellate-cells-in-mice-via-nf-%C3%AE%C2%BAb-and-tgf-%C3%AE-1-smad3-pathways
#20
Jiao Feng, Kan Chen, Yujing Xia, Liwei Wu, Jingjing Li, Sainan Li, Wenwen Wang, Xiya Lu, Tong Liu, Chuanyong Guo
Purpose: Liver fibrosis is commonly seen and a necessary stage in chronic liver disease. The aim of this study was to explore the effect of salidroside on liver fibrosis in mice and its potential mechanisms. Materials and methods: Two mouse liver fibrosis models were established by intraperitoneal injection of carbon tetrachloride (CCl4 ) for 8 weeks and bile duct ligation for 14 days. Salidroside was injected intraperitoneally at doses of 10 and 20 mg/kg once a day...
2018: Drug Design, Development and Therapy
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