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https://www.readbyqxmd.com/read/28445938/pirfenidone-normalizes-the-tumor-microenvironment-to-improve-chemotherapy
#1
Christiana Polydorou, Fotios Mpekris, Panagiotis Papageorgis, Chrysovalantis Voutouri, Triantafyllos Stylianopoulos
Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis, to investigate its possible role on tumor microenvironment normalization...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444922/regulation-of-organelle-function-by-metformin
#2
REVIEW
Jeongho Kim, Young-Jai You
Metformin ameliorates hyperglycemia without the side effects of lactic acidosis or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic glucose production in the liver and by increasing glucose uptake in the muscle. Recent studies show that metformin induces cell death in certain cancer cell lines by interfering with the metabolism of the cancer cells. Therefore, understanding the mechanisms of action for metformin will provide insights into how to better treat diabetes and other metabolic disorders and also into the development of new therapeutic drugs...
April 26, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28444760/vancomycin-levels-are-frequently-subtherapeutic-in-critically-ill-patients-a-prospective-observational-study
#3
V Bakke, H Sporsem, E Von der Lippe, I Nordøy, Y Lao, H C Nyrerød, L Sandvik, K R Hårvig, J F Bugge, E Helset
BACKGROUND: Appropriate utilization of vancomycin is important to attain therapeutic targets while avoiding clinical failure and the development of antimicrobial resistance. Our aim was to observe the use of vancomycin in an intensive care population, with the main focus on achievement of therapeutic serum concentrations (15-20 mg/l) and to evaluate how this was influenced by dose regimens, use of guidelines and therapeutic drug monitoring. METHODS: A prospective observational study was carried out in the intensive care units at two tertiary hospitals in Norway...
April 25, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/28444472/the-effect-of-sodium-glucose-co-transporter-2-sglt-2-inhibitors-on-cardiometabolic-profile-beyond-the-hypoglycaemic-action
#4
Eirini Lioudaki, Emmanouil S Androulakis, Martin Whyte, Konstantinos G Stylianou, Eugenios K Daphnis, Emmanouil S Ganotakis
Type 2 diabetes mellitus (T2DM) has growing prevalence worldwide and major clinical implications, chiefly cardiovascular (CV) and renal disease burden. Sodium-glucose co-transporter (SGLT)-2 inhibitors are a new drug class in the management of T2DM with a mechanism of action independent of insulin. In addition to their hypoglycaemic effect, SGLT-2 inhibitors appear to have haemodynamic and nephroprotective effects. Studies have consistently showed a modest but significant blood pressure (BP) reduction. Metabolic benefits are also attributed to SGLT-2 inhibitors with a modest but consistent body weight decrease recorded along with improvements in lipid profile and uric acid levels...
April 25, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28443385/pseudomonas-aeruginosa-prevalence-antibiotic-resistance-and-antimicrobial-use-in-chinese-burn-wards-from-2007-to-2014
#5
Yi Dou, Jingning Huan, Feng Guo, Zengding Zhou, Yan Shi
Objective To assess the application of antibacterial agents, alongside pathogen prevalence and Pseudomonas aeruginosa drug resistance, with the aim of understanding the impact of inappropriate antibacterial use. Methods This retrospective study assessed bacteria from wounds, catheters, blood, faeces, urine and sputum of hospitalized patients in burn wards between 2007 and 2014. The intensity of use of antibacterial agents and resistance of P. aeruginosa to common anti-Gram-negative antibiotics were measured...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28442937/simultaneous-administration-of-fluoxetine-and-simvastatin-ameliorates-lipid-profile-improves-brain-level-of-neurotransmitters-and-increases-bioavailability-of-simvastatin
#6
Abdulrahman K Al-Asmari, Zabih Ullah, Aqeel Salman Al Masoudi, Ishtiaque Ahmad
Simvastatin (STT), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is widely prescribed for dyslipidemia, whereas fluoxetine (FLX) is the first-choice drug for the treatment of depression and anxiety. A recent report suggests that selective serotonin reuptake inhibitors can interact with the cytochrome P450 3A4 substrate, and another one suggests that STT enhances the antidepressant activity of FLX. However, the data are inconclusive. The present study was designed to explore the pharmacokinetic and pharmacodynamic consequences of coadministration of STT and FLX in experimental animals...
2017: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/28442538/peripheral-tumor-necrosis-factor-alpha-tnf-%C3%AE-modulates-amyloid-pathology-by-regulating-blood-derived-immune-cells-and-glial-response-in-the-brain-of-ad-tnf-transgenic-mice
#7
Evi Paouri, Ourania Tzara, Georgia-Ioanna Kartalou, Sofia Zenelak, Spiros Georgopoulos
Increasing evidence has suggested that systemic inflammation along with local brain inflammation can play a significant role in Alzheimer's disease (AD) pathogenesis. Identifying key molecules that regulate the crosstalk between the immune and the central nervous system can provide potential therapeutic targets. TNF-α is a pro-inflammatory cytokine implicated in the pathogenesis of systemic inflammatory and neurodegenerative diseases such as rheumatoid arthritis (RA) and AD. Recent studies have reported that anti-TNF-α therapy or RA itself can modulate AD pathology, although the underlying mechanism is unclear...
April 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28442507/protein-kinase-stk25-aggravates-the-severity-of-non-alcoholic-fatty-pancreas-disease-in-mice
#8
Esther Nunez Duran, Belen Chanclon, Silva Sütt, Joana Real, Hanns-Ulrich Marschall, Ingrid Wernstedt-Asterholm, Emelie Cansby, Margit Mahlapuu
Characterising the molecular networks that negatively regulate pancreatic β-cell function is essential for understanding the underlying pathogenesis and developing new treatment strategies for type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic fat storage, meta-inflammation, and fibrosis in liver and skeletal muscle. Here, we assessed the role of STK25 in control of progression of non-alcoholic fatty pancreas disease in the context of chronic exposure to dietary lipids in mice...
April 25, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28442108/effect-of-egyptian-propolis-on-cryptosporidiosis-in-immunosuppressed-rats-with-special-emphasis-on-oocysts-shedding-leukogram-protein-profile-and-ileum-histopathology
#9
Hamdy Soufy, Nadia M El-Beih, Soad M Nasr, Tamer H Abd El-Aziz, Fathia A M Khalil, Youssef F Ahmed, Hala A A Abou Zeina
OBJECTIVES: To investigate the activity of Egyptian propolis extracts (ethanol and water) on cryptosporidiosis in experimentally infected dexamethasone-immunosuppressed rats. METHODS: A total of 180 male rats (190-220) g BWt were randomly divided into 9 equal groups (G1-G9). Groups of rats were kept as (G1): normal control, (G2-G9): immunosuppressed with dexamethasone and (G3-G9): infected with Cryptosporidium oocysts. Rats from (G4-G9) were given orally ethanol and water extract of propolis (at a dose of 50 mg/kg BWt) and nitazoxanide (standard anti-cryptosporidial drug at a dose of 100 mg/kg BWt) to infected rats with different regimes...
March 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28441653/effect-of-topical-iloprost-and-nitroglycerin-on-gastric-microcirculation-and-barrier-function-during-hemorrhagic-shock-in-dogs
#10
Richard Truse, Jonas Hinterberg, Jan Schulz, Anna Herminghaus, Andreas Weber, Tabea Mettler-Altmann, Inge Bauer, Olaf Picker, Christian Vollmer
BACKGROUND: Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions. METHODS: In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously...
April 26, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28441588/reduced-ena78-levels-as-novel-biomarker-for-major-depressive-disorder-and-venlafaxine-efficiency-result-from-a-prospective-longitudinal-study
#11
Zezhi Li, Zuowei Wang, Chen Zhang, Jun Chen, Yousong Su, Jia Huang, Zhenghui Yi, Chengmei Yuan, Wu Hong, Yong Wang, Zhiguo Wu, Yingyan Hu, Lan Cao, Daihui Peng, Yangtai Guan, Yimin Zou, Shunying Yu, Donghong Cui, Yiru Fang
Although lines of evidence demonstrated that cytokines play an important role in the pathogenesis of major depressive disorder (MDD), none of the them have been established as reliable biomarkers. We use our previous whole-genome cRNA microarray data to identify epithelial cell-derived neutrophil-activating peptide 78 (ENA78), the most differentially expressed cytokine in peripheral blood between MDD patients and healthy controls; and then we confirmed the result by the quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) for mRNA and protein level, respectively, in an independent drug-naïve first-episode sample set...
March 18, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28440968/the-effects-of-active-hexose-correlated-compound-ahcc-on-levels-of-cd4-and-cd8-in-patients-with-epithelial-ovarian-cancer-or-peritoneal-cancer-receiving-platinum-based-chemotherapy
#12
Wineeya Suknikhom, Ruangsak Lertkhachonsuk, Tarinee Manchana
Background: Adjuvant chemotherapy is a required treatment for most patients with epithelial ovarian cancer (EOC) or peritoneal cancer. However, it has many adverse events which may affect oncologic outcomes. Active hexose correlated compound (AHCC) has been reported to be an immunoenhancer to decrease adverse events of chemotherapy. Materials and Methods: Patients were randomized and allocated to receive either AHCC three grams/day (500mg/ capsule) or placebo. These drugs were administrated as two capsules orally three times a day throughout six cycles of chemotherapy...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28440768/clinical-and-metabolic-profile-of-patients-with-latent-autoimmune-diabetes-in-adults-in-specialized-care-in-madrid
#13
Alfonso Arranz Martín, Edurne Lecumberri Pascual, Miguel Ángel Brito Sanfiel, Víctor Andía Melero, Lia Nattero Chavez, Iván Sánchez López, Gloria Cánovas Molina, Francisco Arrieta Blanco, Noemí González Perez Del Villar
OBJECTIVE: To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. METHODS: Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed...
January 2017: Endocrinol Diabetes Nutr
https://www.readbyqxmd.com/read/28440745/primaquine-in-plasma-and-methemoglobinemia-in-patients-with-malaria-due-to-plasmodium-vivax-in-the-brazilian-amazon-basin
#14
José Luiz Vieira, Michelle E S Ferreira, Michelle V D Ferreira, Margarete M Gomes
Primaquine is the only licensed drug available for the elimination of Plasmodium vivax hypnozoites. Methemoglobinemia is currently reported in the course of treatment. There is evidence that metabolites of primaquine formed by the cytochrome pathway are responsible for methemoglobin formation; a genetic polymorphism of cytochrome isoforms; and a potential influence of gender in the activities of these enzymes requiring the establishment of dose × response curves profiles in different population groups. Concentrations of primaquine in plasma and methemoglobin levels were investigated in 54 patients with malaria due to P...
April 3, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28440068/correlates-of-verbal-and-physical-aggression-among-patrons-of-licensed-venues-in-australia
#15
Shannon Hyder, Kerri Coomber, Amy Pennay, Nicolas Droste, Ashlee Curtis, Richelle Mayshak, Tina Lam, William Gilmore, Tanya Chikritzhs, Peter G Miller
INTRODUCTION AND AIMS: The current study aimed to examine the association between patron demographics and substance use, and experiences of verbal and physical aggressive incidents within the last 3 months among patrons of night-time entertainment precincts (NEP) in Australia. DESIGN AND METHODS: Patron interviews (n = 4216) were conducted around licensed venues in the NEPs of five Australian cities. Seven correlates of verbal and physical aggressive incidents were examined: gender, age, occupation, blood alcohol concentration, pre-drinking, energy drink use and illicit drug use in the current session...
April 25, 2017: Drug and Alcohol Review
https://www.readbyqxmd.com/read/28439456/metformin-ameliorates-insulitis-in-stz-induced-diabetic-mice
#16
Xue Han, Yu-Long Tao, Ya-Ping Deng, Jia-Wen Yu, Jian Cai, Guo-Fei Ren, Yuan-Nan Sun, Guo-Jun Jiang
BACKGROUND & AIMS: Metformin is currently the most widely used first-line hypoglycemic agent for diabetes mellitus. Besides glucose-lowering action, there is increasingly interest in the potential anti-inflammatory action of this drug. In the present study, we investigated the actions of metformin on experimental insulitis using STZ-induced diabetic mice. METHODS: Mice with acute diabetes induced by STZ were administered metformin by gavage. Changes of blood glucose and body weight, and the daily amount of food and water intake were measured...
2017: PeerJ
https://www.readbyqxmd.com/read/28439167/comparative-evaluation-of-c-reactive-protein-and-wbc-count-in-fascial-space-infections-of-odontogenic-origin
#17
Ravikiran Bagul, Sanjay Chandan, Vikrant Dilip Sane, Sujay Patil, Dinesh Yadav
PURPOSE: To assess efficacy of C-reactive protein levels as monitoring tools for patients with fascial space infections of odontogenic origin. MATERIAL AND METHOD: A randomized prospective study was conducted on 20 patients suffering from fascial space infection of odontogenic origin, in the department of Oral and Maxillofacial Surgery Bharati Vidyapeeth dental college and hospital, Pune, Patients between 18 and 60 years of age of both the sexes were selected. All patients were treated and observed by the same surgeon...
June 2017: Journal of Maxillofacial and Oral Surgery
https://www.readbyqxmd.com/read/28439107/e-selectin-ligands-recognised-by-heca452-induce-drug-resistance-in-myeloma-which-is-overcome-by-the-e-selectin-antagonist-gmi-1271
#18
A Natoni, T A G Smith, N Keane, C McEllistrim, C Connolly, A Jha, M Andrulis, E Ellert, M S Raab, S V Glavey, L Kirkham-McCarthy, S K Kumar, S C Locatelli-Hoops, I Oliva, W E Fogler, J L Magnani, M E O'Dwyer
Multiple Myeloma (MM) is characterized by the clonal expansion and metastatic spread of malignant plasma cells to multiple sites in the bone marrow (BM). Recently, we implicated the sialyltransferase ST3Gal-6, an enzyme critical to the generation of E-selectin ligands, in MM BM homing and resistance to therapy. Since E-selectin is constitutively expressed in the BM microvasculature, we wished to establish the contribution of E-selectin ligands to MM biology. We report that functional E-selectin ligands are restricted to a minor subpopulation of MM cell lines which, upon expansion, demonstrate specific and robust interaction with recombinant E-selectin in vitro...
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28438386/catabolism-of-antibody-drug-conjugates-and-characterization-methods
#19
REVIEW
Mohammad Shadid, Stephen Bowlin, Jayaprakasam Bolleddula
Antibody drug conjugates (ADCs) are large molecule therapeutics in which a cytotoxic payload is conjugated to a monoclonal antibody (mAb) via a linker. The molecules are designed to selectively bind to target-expressing cells, thus delivering therapeutic agents directly to the tumor. Chemical and enzymatic stability prior to reaching the target is an important factor for ADCs since it impacts their safety, efficacy, and pharmacokinetics (PK). One of the main reasons for off-target effects of ADCs is premature release of cytotoxic agents, either in the blood stream or at non-specific sites...
April 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28437852/a-diagnostic-microdosing-approach-to-investigate-platinum-sensitivity-in-non-small-cell-lung-cancer
#20
Si-Si Wang, Maike Zimmermann, Hongyong Zhang, Tzu-Yin Lin, Michael Malfatti, Kurt Haack, Kenneth W Turteltaub, George D Cimino, Ralph de Vere White, Chong-Xian Pan, Paul T Henderson
The platinum-based drugs cisplatin, carboplatin and oxaliplatin are often used for chemotherapy, but drug resistance is common. The prediction of resistance to these drugs via genomics is a challenging problem since hundreds of genes are involved. A possible alternative is to use mass spectrometry to determine the propensity for cells to form drug-DNA adducts-the pharmacodynamic drug-target complex for this class of drugs. The feasibility of predictive diagnostic microdosing was assessed in non-small cell lung cancer (NSCLC) cell culture and a pilot clinical trial...
April 24, 2017: International Journal of Cancer. Journal International du Cancer
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