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https://www.readbyqxmd.com/read/28636290/sulforaphane-protection-against-the-development-of-doxorubicin-induced-chronic-heart-failure-is-associated-with-nrf2-upregulation
#1
Yang Bai, Qiang Chen, Yun-Peng Sun, Xuan Wang, Li Lv, Li-Ping Zhang, Jin-Sha Liu, Song Zhao, Xiao-Lu Wang
Doxorubicin (DOX) is an anthracycline anti-tumor drug. However, its clinical use is limited by dose-dependent cardiotoxicity, and even progresses to chronic heart failure (CHF). OBJECTIVE: This study aims to investigate whether the Nrf2 activator, sulforaphane (SFN), can prevent DOX-induced CHF. METHODS: Male Sprague Dawley rats who received treatment for six weeks were divided into four groups (n=30 per group): control, SFN, DOX, and DOX plus SFN group. RESULTS: Results revealed that DOX induced progressive cardiac damage as indicated by increased cardiac injury markers, cardiac inflammation, fibrosis and oxidative stress...
June 21, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28636269/commentary-on-r-d-trends-away-from-general-medicine-cardiovascular-drugs-can-the-fda-help-reverse-the-trend
#2
R J Meyer
In the latter part of the 20th century, drug development in cardiovascular diseases (CVDs) was a paragon of "modern" therapeutics, bringing about a substantial number of effective, well-tolerated agents targeting some of the most prevalent diseases of the Western world. These drugs were often examples of rational drug development targeting specific pathophysiologic pathways previously elucidated through basic research (e.g., targeting of the renin-angiotensin system or the cholesterol synthesis pathway). The widespread adoption of these ground-breaking medications in practice and into medical guidelines undoubtedly played a role in the fall of morbidity and mortality from CVD in the United States in recent decades...
June 21, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28636254/pirfenidone-reduces-subchondral-bone-loss-and-fibrosis-after-murine-knee-cartilage-injury
#3
Deva D Chan, Jun Li, Wei Luo, Dan N Predescu, Brian J Cole, Anna Plaas
Pirfenidone is an anti-inflammatory and anti-fibrotic drug that has shown efficacy in lung and kidney fibrosis. Because inflammation and fibrosis have been linked to the progression of osteoarthritis, we investigated the effects of oral Pirfenidone in a mouse model of cartilage injury, which results in chronic inflammation and joint-wide fibrosis in mice that lack hyaluronan synthase 1 (Has1(-/-) ) in comparison to wild-type. Femoral cartilage was surgically injured in wild-type and Has1(-/-) mice, and Pirfenidone was administered in food starting after 3 days...
June 21, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28636222/recent-progress-in-immunotherapy-for-urological-cancer
#4
REVIEW
Wataru Obara, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata
Cancer immunotherapy for urological tumors had made progress for several decades, but recent advances in immunotherapy, as therapeutic vaccines or immune checkpoint inhibitors, have drastically changed the present treatment strategy. Recently, nivolumab and atezolizumab have been approved by the Food and Drug Administration for treatment of urological cancers. Additional immune checkpoint inhibitors and vaccines are being tested in clinical trials. Despite advances in these therapeutic modalities, benefits are limited to a subset of patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28636208/a-phase-i-trial-of-prn1008-a-novel-reversible-covalent-inhibitor-of-bruton-s-tyrosine-kinase-in-healthy-volunteers
#5
Patrick F Smith, Janakan Krishnarajah, Philip A Nunn, Ron J Hill, Dane Karr, D Tam, Mohammad Masjedizadeh, Jens O Funk, Steve G Gourlay
AIM: To evaluate the safety, tolerability, and PK/PD of PRN1008, a novel BTK inhibitor, in healthy volunteers, and thus determine the dose range for future clinical studies. METHODS: This was a two-part randomized, placebo controlled study in healthy volunteers using a liquid formulation. Part I was a single ascending dose design with dose levels of 50 to 1200 mg (n=6 active, 2 placebo per cohort); Part II was a multiple ascending dose design, with dose regimens ranging from 300 mg to 900 mg daily, either qd or bd for 10 days...
June 21, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28636191/-fast-track-development-and-approval-process-for-heart-failure-therapeutics
#6
L Papadimitriou, J Butler
Heart failure (HF) is a global epidemic, with a high mortality and morbidity burden. In such diseases, earlier access to lifesaving therapeutic regimens is imperative, and could be accomplished by improving the drug development and approval process, without jeopardizing patient safety. The US Food and Drug Administration (FDA) has already established mechanisms facilitating the latter, but further guidance to enhance and expedite the process holds promise to further improve patient outcomes.
June 21, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28636189/discovery-of-alkyl-bis-oxy-dibenzimidamide-derivatives-as-novel-protein-arginine-methyltransferase-1-prmt1-inhibitors
#7
Wei-Yao Zhang, Wen-Chao Lu, Hao Jiang, Zheng-Bing Lv, Yi-Qian Xie, Fu-Lin Lian, Zhong-Jie Liang, Yu-Xi Jiang, Da-Jin Wang, Cheng Luo, Jia Jin, Fei Ye
Protein arginine methylation, a post-translational modification critical for a variety of biological processes, is catalyzed by protein arginine N-methyltransferases (PRMTs). In particular, PRMT1 is responsible for over 85% of the arginine methylation in mammalian cells. Dysregulation of PRMT1 is involved in diverse pathological diseases including cancers. However, most current PRMT1inhibitors are lack of specificity, efficacy, and bioavailability. Herein, a series of alkyl bis(oxy)dibenzimidamide derivatives were identified as selective PRMT1 inhibitors...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28636184/pharmacokinetics-pharmacodynamics-of-bococizumab-a-monoclonal-antibody-to-pcsk9-after-single-subcutaneous-injection-at-3-sites-nct-02043301
#8
Ellen Q Wang, Anna Plotka, Joanne Salageanu, Catherine Sattler, Carla Yunis
AIM: To characterize the single-dose pharmacokinetics (PK) and pharmacodynamics (PD) of bococizumab, a monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), administered subcutaneously (s.c.) to the abdomen, thigh, or upper arm (NCT02043301). METHODS: Seventy-five adults with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and not on background lipid-lowering therapy were randomized (1:1:1) to a single 150-mg s.c. dose of bococizumab administered to the abdomen, thigh, or upper arm...
June 21, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28636163/the-pu-prom-a-patient-reported-outcome-measure-for-peptic-ulcer-disease
#9
Na Liu, Jing Lv, Jinchun Liu, Yanbo Zhang
OBJECTIVE: Patient-reported outcome measure (PROM) conceived to enable description of treatment-related effects, from the patient perspective, bring the potential to improve in clinical research, and to provide patients with accurate information. Therefore, the aim of this study was to develop a patient-centred peptic ulcer patient-reported outcome measure (PU-PROM) and evaluate its reliability, validity, differential item functioning (DIF) and feasibility. METHOD: To develop a conceptual framework and item pool for the PU-PROM, we performed a literature review and consulted other measures created in China and other countries...
June 21, 2017: Health Expectations: An International Journal of Public Participation in Health Care and Health Policy
https://www.readbyqxmd.com/read/28636149/photocatalytic-interaction-of-aminophylline-riboflavin-leads-to-ros-mediated-dna-damage-and-cell-death-a-novel-phototherapeutic-mechanism-for-cancer
#10
Saniyya Khan, Imrana Naseem
The accompanied tissue devastation and systemic toxicity of chemotherapy has shifted the quest for having an effective and palliative cancer therapy towards photodynamic therapy (PDT). Riboflavin (Rf), an essential micronutrient is emerging as a potent tool of PDT, due to its excellent photosensitizing properties. It can be used as an efficient adjuvant for various anticancer drugs. The hemolytic and proteolytic effect of photoilluminated aminophylline (Am), a xanthine derivative, and Rf is well documented in literature...
June 21, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28636142/clinical-development-of-immunotherapy-for-prostate-cancer
#11
REVIEW
Masanori Noguchi, Noriko Koga, Tsukasa Igawa, Kyogo Itoh
Prostate cancer is the most common cancer in men, and the second leading cause of cancer-related death in Western countries. Prostate cancer-related death occurs in patients with metastatic castration-resistant prostate cancer. Although several new drugs for castration-resistant prostate cancer have been approved, each of these has prolonged survival by just a few months. Consequently, new therapies are sorely needed. Recently, it has been recognized that immunotherapy is an effective treatment for prostate cancer patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28636139/review-of-hplc-and-lc-ms-ms-assays-for-the-determination-of-various-non-steroidal-anti-androgens-nsaa-used-in-the-treatment-of-prostate-cancer
#12
REVIEW
P S Suresh, Nuggehally R Srinivas, Ramesh Mullangi
Prostate cancer is the most common cancer and one of the leading causes for cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first generation non-steroidal anti-androgens (NSAA) namely flutamide, nilutamide, bicalutamide and topilutamide. Most of the prostate cancer patients who are initially responsive develop a most aggressive form of disease called castration-resistant prostate cancer (CRPC). Second generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat CRPC...
June 21, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28636123/sem-imaging-of-the-stimulatory-response-of-raw264-7-cells-against-porphyromonas-gingivalis-using-a-simple-technique-employing-new-conductive-materials
#13
Chisato Takahashi, Yoshiki Umemura, Ayako Naka, Hiromitsu Yamamoto
In the medical biology, it is essential to understand not only biological morphology but also the interaction between biological materials and agents. To study these, electron microscopy (EM) is often utilized. However, sample preparation techniques for EM require a high level of skill and a considerable time. Here, we conducted EM using a simple technique employing a conductive liquid, BEL-1, and compared the results with another simple technique employing an ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4 ])...
June 21, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28636088/multicompartment-drug-release-system-for-dynamic-modulation-of-tissue-responses
#14
Aaron H Morris, Rajwant S Mahal, Jillian Udell, Michelle Wu, Themis R Kyriakides
Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure...
June 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28636084/co-morbidities-and-bleeding-in-elderly-patients-with-haemophilia-a-survey-of-the-german-austrian-and-swiss-society-of-thrombosis-and-haemostasis-research-gth
#15
W Miesbach, S-E Reitter-Pfoertner, R Klamroth, F Langer, H-H Wolf, A Tiede, B Siegmund, U Scholz, P R Müller, H Eichler, I Pabinger
BACKGROUND: Nowadays patients with haemophilia survive longer due to improvements in haemophilia care. It has been hypothesized that the bleeding type and frequency may vary with age and are influenced by co-morbidities and co-medication in elderly patients. OBJECTIVES: To investigate a large group of patients older than 60 years of age with haemophilia concerning haemophilia treatment, bleeding pattern changes, co-morbidities, co-medication, bleeding sites and patient mortality...
June 21, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28636017/effect-of-cisplatin-on-the-transport-activity-of-pii-type-atpases
#16
Francesco Tadini-Buoninsegni, Giacomo Sordi, Serena Smeazzetto, Giovanni Natile, Fabio Arnesano
Cisplatin (cis-diamminedichlorido-Pt(ii)) is extensively used as a chemotherapeutic agent against various types of tumors. However, cisplatin administration causes serious side effects, including nephrotoxicity, ototoxicity and neurotoxicity. It has been shown that cisplatin can interact with P-type ATPases, e.g., Cu(+)-ATPases (ATP7A and ATP7B) and Na(+),K(+)-ATPase. Cisplatin-induced inhibition of Na(+),K(+)-ATPase has been related to the nephrotoxic effect of the drug. To investigate the inhibitory effects of cisplatin on the pumping activity of PII-type ATPases, electrical measurements were performed on sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+),K(+)-ATPase embedded in vesicles/membrane fragments adsorbed on a solid-supported membrane...
June 21, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28636001/wataa-atlas-of-protein-hydration-exploring-synergies-between-data-mining-and-ab-initio-calculations
#17
Jiří Černý, Bohdan Schneider, Lada Biedermannová
Water molecules represent an integral part of proteins and a key determinant of protein structure, dynamics and function. WatAA is a newly developed, web-based atlas of amino-acid hydration in proteins. The atlas provides information about the ordered first hydration shell of the most populated amino-acid conformers in proteins. The data presented in the atlas are drawn from two sources: experimental data and ab initio quantum-mechanics calculations. The experimental part is based on a data-mining study of a large set of high-resolution protein crystal structures...
June 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28635967/social-behaviour-involving-drug-resistance-the-role-of-initial-density-initial-frequency-and-population-structure-in-shaping-the-effect-of-antibiotic-resistance-as-a-public-good
#18
I L Domingues, J A Gama, L M Carvalho, F Dionisio
Bacteria sometimes cooperate with co-inhabiting cells. Pathogenic bacteria, for example, often produce and excrete virulence factors, eventually benefitting both producer and non-producer cells. The role of social interactions involving antibiotic resistance, however, has been more elusive. Enzymes that inactivate β-lactam antibiotics such as ampicillin or penicillin (β-lactamases) are good candidates as public goods. Nonetheless, it has been claimed that bacteria harbouring plasmids of natural origin coding for β-lactamase almost do not protect sensitive bacteria...
June 21, 2017: Heredity
https://www.readbyqxmd.com/read/28635961/hypoxia-induced-mobilization-of-nhe6-to-the-plasma-membrane-triggers-endosome-hyperacidification-and-chemoresistance
#19
Fabrice Lucien, Pierre-Paul Pelletier, Roxane R Lavoie, Jean-Michel Lacroix, Sébastien Roy, Jean-Luc Parent, Dominique Arsenault, Kelly Harper, Claire M Dubois
The pH-dependent partitioning of chemotherapeutic drugs is a fundamental yet understudied drug distribution mechanism that may underlie the low success rates of current approaches to counter multidrug resistance (MDR). This mechanism is influenced by the hypoxic tumour microenvironment and results in selective trapping of weakly basic drugs into acidified compartments such as the extracellular environment. Here we report that hypoxia not only leads to acidification of the tumour microenvironment but also induces endosome hyperacidification...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635907/-the-problem-of-obstructive-sleep-apnea-syndrome-in-asthmatic-patients
#20
E G Sheludko, D E Naumov, Yu M Perelman, V P Kolosov
Asthma and obstructive sleep apnea syndrome (OSAS) are one of the most common chronic respiratory diseases. These have common risk factors that include obesity, gastroesophageal reflux disease (GERD) and impaired nasal breathing (allergic rhinitis, sinusitis). At the same time, experimental evidence demonstrates common pathophysiological mechanisms of these diseases, such as involvement in the process of the respiratory tract, a systemic inflammatory response, and implementation of neuromechanical reflexes...
2017: Terapevticheskiĭ Arkhiv
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