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Systems pharmacology

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https://www.readbyqxmd.com/read/29342359/semiconducting-photothermal-nanoagonist-for-remote-controlled-specific-cancer-therapy
#1
Xu Zhen, Chen Xie, Yuyan Jiang, Xiangzhao Ai, Bengang Xing, Kanyi Pu
Nanomedicines have shown success in cancer therapy, but the pharmacological actions of most nanomedicine are often nonspecific to cancer cells because of utilization of the therapeutic agents that induce cell apoptosis from inner organelles. We herein report the development of semiconducting photothermal nanoagonists that can remotely and specifically initiate the apoptosis of cancer cells from cell membrane. The organic nanoagonists comprise semiconducting polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally-responsive nanocarrier and the agonist for activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), respectively...
January 17, 2018: Nano Letters
https://www.readbyqxmd.com/read/29341979/wilson-s-disease-in-children-a-position-paper-by-the-european-society-for-paediatric-gastroenterology-hepatology-and-nutrition-committee
#2
Piotr Socha, Wojciech Janczyk, Anil Dhawan, Ulrich Baumann, Lorenzo D'Antiga, Stuart Tanner, Raffaele Iorio, Pietro Vajro, Roderick Houwen, Björn Fischler, Antal Dezsofi, Nedim Hadzic, Loreto Hierro, Jörg Jahnel, Valérie McLin, Valerio Nobili, Francoise Smets, Henkjan J Verkade, Dominique Debray
BACKGROUND: Clinical presentations of Wilson's disease (WD) in childhood ranges from asymptomatic liver disease to cirrhosis or acute liver failure, while neurological and psychiatric symptoms are rare. The basic diagnostic approach includes serum ceruloplasmin and 24h-urinary copper excretion. Final diagnosis of WD can be established using a diagnostic scoring system based on symptoms, biochemical tests assessing copper metabolism and molecular analysis of mutations in the ATP7B gene...
October 26, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29341808/development-of-an-open-access-web-based-interactive-tool-to-learn-autonomic-nervous-system-physiology-and-pharmacology
#3
Aydin Zahedivash, Michael W Lee
No abstract text is available yet for this article.
March 1, 2018: Advances in Physiology Education
https://www.readbyqxmd.com/read/29341478/translational-systems-pharmacology-based-predictive-assessment-of-drug-induced-cardiomyopathy
#4
Dimitris E Messinis, Ioannis N Melas, Junguk Hur, Navya Varshney, Leonidas G Alexopoulos, Jane P F Bai
Drug-induced cardiomyopathy contributes to drug attrition. We compared two pipelines of predictive modeling: (1) applying elastic net (EN) to differentially expressed genes (DEGs) of drugs; (2) applying integer linear programming (ILP) to construct each drug's signaling pathway starting from its targets to downstream proteins, to transcription factors, and to its DEGs in human cardiomyocytes, and then subjecting the genes/proteins in the drugs' signaling networks to EN regression. We classified 31 drugs with availability of DEGs into 13 toxic and 18 nontoxic drugs based on a clinical cardiomyopathy incidence cutoff of 0...
January 17, 2018: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29341450/characterization-of-a-novel-papain-inducible-murine-model-of-eosinophilic-rhinosinusitis
#5
Anuj Tharakan, Alex Dobzanski, Nyall R London, Syed M Khalil, Nitya Surya, Andrew P Lane, Murugappan Ramanathan
BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a disease characterized by eosinophilic inflammatory infiltrate and a local type 2 cytokine milieu. Current animal models fail to recapitulate many of the innate and adaptive immunologic hallmarks of the disease, thus hindering the development of effective therapeutics. In the present study, mice were exposed intranasally to the cysteine protease papain, which shares functional similarities with parasitic proteases and aeroallergens, to generate a rapidly inducible murine model of eosinophilic rhinosinusitis...
January 17, 2018: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/29341047/german-guideline-for-idiopathic-pulmonary-fibrosis-update-on-pharmacological-therapies-2017
#6
Jürgen Behr, Andreas Günther, Francesco Bonella, Klaus Geißler, Dirk Koschel, Michael Kreuter, Antje Prasse, Nicolas Schönfeld, Helmut Sitter, Joachim Müller-Quernheim, Ulrich Costabel
Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a median survival of 2 - 4 years after diagnosis. Since the publication of the German IPF guideline in 2013 new treatment trials have been published, necessitating an update of the pharmacological therapy of IPF. Different from the previous guideline, the GRADE system was discarded and replaced by the Oxford evidence classification system which allows a more differentiated judgement. The following pharmacological therapies were rated not suitable for the treatment of IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone, azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan...
January 16, 2018: Pneumologie
https://www.readbyqxmd.com/read/29341031/getting-more-than-you-paid-for-unauthorized-natural-substances-in-herbal-food-supplements-on-eu-market
#7
Marijana Zovko Končić
As the population in the industrialized world develops preference for what is perceived as a natural and holistic way of disease treatment, the popularity and the number of food supplements on the market, including herbal ones, is experiencing an unprecedented rise. However, unlike herbal medicinal products, intended for treating or preventing disease, current legislation classifies food supplements as products intended for achieving nutritional or physiological effect and to supplement the normal diet. Accordingly, most food supplements are not to be associated with specific health claims...
January 16, 2018: Planta Medica
https://www.readbyqxmd.com/read/29340974/inhibiting-6-phosphogluconate-dehydrogenase-selectively-targets-breast-cancer-through-ampk-activation
#8
Xiaoyu Yang, Xiaochun Peng, Jiangrong Huang
PURPOSE: 6-phosphogluconate dehydrogenase (6PGD), a key enzyme of the oxidative pentose phosphate pathway, is involved in tumor growth and metabolism. Although high 6PGD activity has been shown to be associated with poor prognosis, its role and therapeutic value in breast cancer remain unknown. METHODS: The levels and roles of 6PGD were analyzed in breast cancer cells and their normal counterparts. The underlying mechanisms of 6PGD's roles are also analyzed. RESULTS: We found that 6PGD is aberrantly activated in breast cancer as shown by its increased transcriptional and translational levels as well as enzyme activity in breast cancer tissues and cell lines compared to normal counterparts...
January 16, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29340871/neurotoxicity-of-prosopis-juliflora-from-natural-poisoning-to-mechanism-of-action-of-its-piperidine-alkaloids
#9
Victor Diogenes Amaral da Silva, André Mario Mendes da Silva, Juliana Helena Castro E Silva, Silvia Lima Costa
Prosopis juliflora was introduced in northeastern Brazil in the 1940s, and since then, it has been available as an alternative for animal nutrition. However, the consumption of P. juliflora as main or sole source of food causes an illness in animals known locally as "cara torta" disease. Cattle and goats experimentally intoxicated presents neurotoxic damage in the central nervous system. Histologic lesions were mainly characterized by vacuolation and loss of neurons in trigeminal motor nuclei. Furthermore, mitochondrial damage in neurons and gliosis was reported in trigeminal nuclei of intoxicated cattle...
January 16, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29339423/immune-protection-against-lethal-fungal-bacterial-intra-abdominal-infections
#10
Elizabeth A Lilly, Melanie Ikeh, Evelyn E Nash, Paul L Fidel, Mairi C Noverr
Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S...
January 16, 2018: MBio
https://www.readbyqxmd.com/read/29339248/recent-trends-of-nanomedicinal-approaches-in-clinics
#11
REVIEW
Fahima Dilnawaz, Sarbari Acharya, Sanjeeb Kumar Sahoo
Nanotechnology has become the indispensable cutting edge science providing solutions to many problems associated with human being. The application of nanotechnology associated to human health "nanomedicine" has revolutionized the drug delivery system by providing improved pharmacological and therapeutic properties of drugs. These advantageous effects of drug loaded nanocarrier systems are embraced by the pharmaceutical industries for the development of different effective nanocarriers. Currently, several drug loaded nanoformulations are approved by the Food and Drug Administration (FDA), and some of them are undergoing clinical trials for the human use...
January 12, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29339170/sub-anesthetic-doses-of-ketamine-attenuate-nicotine-self-administration-in-rats
#12
Amir H Rezvani, Yousef Tizabi, Susan Slade, Bruk Getachew, Edward D Levin
Smoking cessation strategies are of prime medical importance. Despite availability of various pharmacological agents in combating addiction to nicotine, more effective medications are needed. Based on recent findings, the glutamatergic system in the brain may provide novel targets. Here, we evaluated the effects of acute administration of sub-anesthetic doses of ketamine, an NMDA receptor antagonist, in both male and female Sprague-Dawley rats trained to self-administer nicotine. Animals were injected subcutaneously with 5, 7...
January 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29339116/understanding-women-s-subjective-sexual-arousal-within-the-laboratory-definition-measurement-and-manipulation
#13
REVIEW
Ariel B Handy, Amelia M Stanton, Cindy M Meston
INTRODUCTION: Subjective sexual arousal (SSA) is positive, cognitive engagement in sexual activity. SSA is considered an important aspect of the sexual experience, as it has been found to facilitate sexual activity and, in situations of chronically low or absent arousal, potentially cause distress. Despite the clinical implications of SSA, a thorough review of how to manipulate SSA has yet to be conducted. AIM: To review the state of knowledge about SSA in women, including its definition, measurement, and the outcomes of studies attempting to manipulate SSA within a laboratory setting...
January 12, 2018: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/29338724/development-and-validation-of-hptlc-fingerprints-of-three-species-of-alpinia-with-biomarker-galangin
#14
Anuradha S Upadhye, Anagha Rajopadhye, Lourelle Dias
BACKGROUND: Alpinia galanga (L.) Willd. commonly called as Rasna, Greater galangal or Kulinjan is a medicinally important rhizome used in Indian traditional system of medicine to cure a number of ailments. A. galanga is the main source of a galangin -a medicinally important flavanol which has a number of pharmacological properties viz. anti-mutagenic, and anti-inflammatory. Due to the high demand for the rhizome of A. galanga traders are now substituting it with rhizomes of A. calcarata and A...
January 16, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29338458/tenofovir-alafenamide-taf-treatment-of-hbv-what-are-the-unanswered-questions
#15
Mauro Viganò, Alessandro Loglio, Glenda Grossi, Pietro Lampertico
Tenofovir disoproxil fumarate (TDF), an ester prodrug of tenofovir (TFV), is one of the recommended drugs for chronic hepatitis B (CHB) patients. However, reduced kidney function and loss of bone mineral density have been reported in some CHB patients treated with TDF. Consequent to these safety issues, tenofovir alafenamide (TAF) [Vemlidy®], a phosphonate prodrug of TFV, was developed for the treatment of CHB patients. Areas covered: The favourable pharmacological profile of TAF allows a marked reduction in dosage (25 mg/day) thus reducing systemic exposure to tenofovir and improving the bone and renal safety, keeping however the same virological efficacy, compared to TDF 300 mg/day...
January 17, 2018: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/29338427/lipid-nanoparticles-for-intranasal-administration-application-to-nose-to-brain-delivery
#16
Luigi Battaglia, Pier Paolo Panciani, Elisabetta Muntoni, Maria Teresa Capucchio, Elena Biasibetti, Pasquale De Bonis, Silvia Mioletti, Marco Fontanella, Shankar Swaminathan
The blood brain barrier is a functional barrier allowing the entry into the brain of only essential nutrients, excluding other molecules. Its structure, although essential to keep the harmful entities out, is also a major roadblock for pharmacological treatment of brain diseases. Several alternative invasive drug delivery approaches, such as transcranial drug delivery and disruption of blood brain barrier have been explored, with limited success and several challenges. Intranasal delivery is a non-invasive methodology, which bypasses the systemic circulation, and, through the intra- and extra- neuronal pathways, provides direct brain drug delivery...
January 17, 2018: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29337857/low-molecular-weight-chitosan-insulin-complexes-solubilized-in-a-mixture-of-self-assembled-labrosol-and-plurol-oleaque-and-their-glucose-reduction-activity-in-rats
#17
Amani M Elsayed, Aseel H Khaled, Mayyas M Al Remawi, Nidal A Qinna, Hussam Abu Farsakh, Adnan A Badwan
Oral insulin delivery that better mimics physiological pathways is a necessity as it ensures patient comfort and compliance. A system which is based on a vehicle of nano order where positively charged chitosan interacts with negatively charged insulin and forms a polyelectrolyte complex (PEC) solubilizate, which is then solubilized into an oily phase of oleic acid, labrasol, and plurol oleaque-protects insulin against enzymatic gastrointestinal reduction. The use of an anionic fatty acid in the oily phase, such as oleic acid, is thought to allow an interaction with cationic chitosan, hence reducing particle size...
January 16, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29337673/evaluation-of-immunomodulatory-effects-of-lamotrigine-in-balb-c-mice
#18
Eman Y Abu-Rish, Shada Y Elhayek, Yehia S Mohamed, Islam Hamad, Yasser Bustanji
Modulation of the immune system has recently been shown to be involved in the pharmacological effects of old antiepileptic drugs and in the pathogenesis of epilepsy. Therefore, the most recent guidelines for immunotoxicological evaluation of drugs were consulted to investigate the immunomodulatory effects of lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in vivo effects of lamotrigine on delayed-type hypersensitivity (DTH) response to sheep red blood cell (SRBC) antigens, hemagglutination titer assays and hematological changes...
December 20, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/29337310/oatp1b2-deficiency-protects-against-paclitaxel-induced-neurotoxicity
#19
Alix F Leblanc, Jason A Sprowl, Paola Alberti, Alessia Chiorazzi, W David Arnold, Alice A Gibson, Kristen W Hong, Marissa S Pioso, Mingqing Chen, Kevin M Huang, Vamsi Chodisetty, Olivia Costa, Tatiana Florea, Peter de Bruijn, Ron H Mathijssen, Raquel E Reinbolt, Maryam B Lustberg, Lara E Sucheston-Campbell, Guido Cavaletti, Alex Sparreboom, Shuiying Hu
Paclitaxel is among the most widely used anticancer drugs and is known to cause a dose-limiting peripheral neurotoxicity, the initiating mechanisms of which remain unknown. Here, we identified the murine solute carrier organic anion-transporting polypeptide B2 (OATP1B2) as a mediator of paclitaxel-induced neurotoxicity. Additionally, using established tests to assess acute and chronic paclitaxel-induced neurotoxicity, we found that genetic or pharmacologic knockout of OATP1B2 protected mice from mechanically induced allodynia, thermal hyperalgesia, and changes in digital maximal action potential amplitudes...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337202/progress-with-covalent-small-molecule-kinase-inhibitors
#20
REVIEW
Zheng Zhao, Philip E Bourne
With reduced risk of toxicity and high selectivity, covalent small-molecule kinase inhibitors (CSKIs) have emerged rapidly. Through the lens of structural system pharmacology, here we review this rapid progress by considering design strategies and the challenges and opportunities offered by current CSKIs.
January 11, 2018: Drug Discovery Today
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