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Drug efficacy

Lauren E Marshall, Roy Koomullil, Andra R Frost, Joel L Berry
A preclinical testing model for cancer therapeutics that replicates in vivo physiology is needed to accurately describe drug delivery and efficacy prior to clinical trials. To develop an in vitro model of breast cancer that mimics in vivo drug/nutrient delivery as well as physiological size and bio-composition, it is essential to describe the mass transport quantitatively. The objective of the present study was to develop in vitro and computational models to measure mass transport from a perfusion system into a 3D extracellular matrix (ECM)...
October 21, 2016: Annals of Biomedical Engineering
F Y Kwok, S Venugobal
BACKGROUND: Induction of anaesthesia with propofol is often associated with a significant decrease in arterial pressure, especially in the older population. The aim of this study is to determine the efficacy of phenylephrine in two different doses i.e. 100mcg and 200mcg, given during induction to counteract the anticipated hypotensive effect of propofol in older patients aged over 55 years. METHODS: Seventy-two ASA physical status I - II patients aged 55 years or older were randomly allocated to group 1 (received propofol mixed with normal saline), group 2 (propofol mixed with 100mcg of phenylephrine) or group 3 (propofol mixed with 200mcg of pheynylphrine)...
August 2016: Medical Journal of Malaysia
Daniel Nichol, Mark Robertson-Tessi, Peter Jeavons, Alexander R A Anderson
Non-genetic variation in phenotypes, or bet-hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet-hedging emerges in the genotype-phenotype mapping through a simple interaction model: a molecular switch. We use simple Chemical Reaction Networks to implement stochastic switches that map gene products to phenotypes and investigate the impact of structurally distinct mappings on the evolution of phenotypic heterogeneity. Bet-hedging naturally emerges within this model and is robust to evolutionary loss through mutations to both the expression of individual genes and to the network itself...
October 21, 2016: Genetics
Jennifer C Cook, Richard H Tran, J Herbert Patterson, Jo E Rodgers
PURPOSE: The pharmacology, clinical efficacy, and safety profiles of evolving therapies for the management of chronic heart failure (HF) and acute decompensated heart failure (ADHF) are described. SUMMARY: HF confers a significant financial burden despite the widespread use of traditional guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone receptor antagonists, and the rates of HF-related mortality and hospitalization have remained unacceptably high...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
Eun-Young Nam, Sun Ah Kim, Heejung Kim, Su-Hyun Kim, Jae-Hyun Han, Ju-Hee Lee, Dong-Il Kim
ETHNOPHARMACOLOGICAL RELEVANCE: Evodiae Fructus (EF) is the dried, unripe fruit of Evodia rutaecarpa Benth., and one of the main components of traditional herbal prescriptions issued for the treatment of sterility caused by irregular menstruation in Korea. However, scientific evidence regarding the efficacy and action mechanism of EF is lacking. AIM OF THE STUDY: In this study, the authors established an in vitro screening tool to identify promising new drug candidates in herbal medicines for the prevention and treatment of premature ovarian failure...
October 18, 2016: Journal of Ethnopharmacology
Jinke Xu, Mifong Tam, Sepideh Samadei, Sophie Lerouge, Jake Barralet, Mary M Stevenson, Marta Cerruti
Mucoadhesive drug delivery systems stick to mucosal tissues and prolong the local retention time of drugs. Since the colon is covered by a mucosal layer, mucoadhesive rectal formulations may improve treatment of such diseases as hypertension or colon cancer. Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the colonic mucosa. It is commonly treated with sulfasalazine (SSZ), which is metabolized by the intestinal flora into the therapeutic 5-aminosalicylic acid (5-ASA) and a toxic by-product sulfapyridine (SP)...
October 18, 2016: Acta Biomaterialia
Nourridine Siewe, Abdul-Aziz Yakubu, Abhay R Satoskar, Avner Friedman
Leishmaniasis is a disease caused by the Leishmania parasites. The two common forms of leishmaniasis are cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). VL is the more severe of the two and, if untreated, may become fatal. The hallmark of VL is the formation of granuloma in the liver or the spleen. In this paper, we develop a mathematical model of the evolution of granuloma in the liver. The model is represented by a system of partial differential equations and it includes migration of cells from the adaptive immune system into the granuloma; the rate of the influx is determined by the strength of the immune response of the infected individual...
October 18, 2016: Journal of Theoretical Biology
Adey A Berhanu, Svetlana Krasnokutsky, Robert T Keenan, Michael H Pillinger
INTRODUCTION: Pegloticase is a highly effective therapy for patients with refractory and/or tophaceous gout, but has a high discontinuation rate (30-50%) due to development of anti-drug antibodies causing loss of efficacy and risk of infusion reactions. OBJECTIVE: To describe the use of azathioprine or other immunosuppressive therapies as a pegloticase adjunct to prevent pegloticase immunogenicity when treating gout. METHODS: Case report of azathioprine use in a patient receiving pegloticase therapy for refractory tophaceous gout, and review of the literature for the impact of immunosuppressive agents on development of anti-drug antibodies...
September 20, 2016: Seminars in Arthritis and Rheumatism
J M Madrid Pérez, P M García Barquín, A J Villanueva Marcos, J I García Bolao, G Bastarrika Alemañ
OBJECTIVE: Radiofrequency ablation is an efficacious alternative in patients with symptomatic atrial fibrillation who do not respond to or are intolerant to at least one class I or class III antiarrhythmic drug. Although radiofrequency ablation is a safe procedure, complications can occur. Depending on the location, these complications can be classified into those that affect the pulmonary veins themselves, cardiac complications, extracardiac intrathoracic complications, remote complications, and those that result from vascular access...
October 18, 2016: Radiología
Ester Fernandez-Salas, Shaomeng Wang, Arul M Chinnaiyan
Castration resistant prostate cancer (CRPC) is a deadly disease with few therapeutic options once patients become resistant to second generation drugs targeting the AR-transcriptional program. The BET-BRD readers of chromatin are key regulators of AR-, ERG-, and c-Myc-mediated transcription in CRPC. BET-BRD inhibitors have demonstrated pre-clinical efficacy in models of CRPC and are currently being evaluated in several clinical trials. These novel drugs have the potential to transform the way we treat CRPC in the near future...
March 2016: Drug Discovery Today. Technologies
Suwanna Chaorattanakawee, Chanthap Lon, Krisada Jongsakul, Jariyanart Gawee, Somethy Sok, Siratchana Sundrakes, Nareth Kong, Chatchadaporn Thamnurak, Soklyda Chann, Sorayut Chattrakarn, Chantida Praditpol, Nillawan Buathong, Nichapat Uthaimongkol, Philip Smith, Narongrid Sirisopana, Rekol Huy, Satharath Prom, Mark M Fukuda, Delia Bethell, Douglas S Walsh, Charlotte Lanteri, David Saunders
BACKGROUND: The recent dramatic decline in dihydroartemisinin-piperaquine (DHA-PPQ) efficacy in northwestern Cambodia has raised concerns about the rapid spread of piperaquine resistance just as DHA-PPQ is being introduced as first-line therapy in neighbouring countries. METHODS: Ex vivo parasite susceptibilities were tracked to determine the rate of progression of DHA, PPQ and mefloquine (MQ) resistance from sentinel sites on the Thai-Cambodian and Thai-Myanmar borders from 2010 to 2015...
October 21, 2016: Malaria Journal
Dominik Madžar, Anna Geyer, Ruben U Knappe, Stephanie Gollwitzer, Joji B Kuramatsu, Stefan T Gerner, Hajo M Hamer, Hagen B Huttner
BACKGROUND: Clobazam (CLB) is a well characterized antiepileptic drug (AED) that differs from other benzodiazepines by its basic chemical structure and pharmacodynamic properties. Only one previous study examined the efficacy of CLB as add-on therapy in refractory status epilepticus (RSE). METHODS: We analyzed RSE episodes treated in our institution between 2001 and 2012. Successful treatment with CLB was scored if CLB was the last AED added to therapy before RSE termination...
October 21, 2016: BMC Neurology
Yuri N Clement, Varune Mahase, Annelise Jagroop, Kelly Kissoon, Aarti Maharaj, Prashant Mathura, Chrys Mc Quan, Divya Ramadhin, Cherrista Mohammed
BACKGROUND: Cancer is a major disease worldwide, and many patients use complementary and alternative treatments. The purpose of this study was to identify the herbal remedies and functional foods used as complementary medicine by prostate, breast and colorectal cancer patients at speciality care facilities in Trinidad. We also sought to determine how patients rated the efficacy of these modalities compared with conventional treatment. METHODS: A descriptive, cross-sectional survey was conducted using an interviewer-administered pilot-tested de novo questionnaire during the period June to August 2012 at two speciality treatment centres on the island...
October 21, 2016: BMC Complementary and Alternative Medicine
Elena S Don, Alexandra G Emelyanova, Natalia N Yakovleva, Nataliia V Petrova, Marina V Nikiforova, Evgeniy A Gorbunov, Sergey A Tarasov, Sergey G Morozov, Oleg I Epstein
The assessment of dose-response is an essential part of drug development in terms of the determination of a drug's effective dose, finding the safety endpoint, estimation of the pharmacokinetic profile and even validation of drug activity, especially for therapeutic agents with a principally novel mechanism of action. Drugs based on released-active forms of antibodies are a good example of such a target. In this study, the efficacy of the antiviral drug Anaferon for children (released-active form of antibodies to interferon-gamma) was tested in a dose-dependent manner (at doses of 0...
October 21, 2016: Journal of Medical Virology
Ryota Saito, Maiko Hoshi, Akihiro Kato, Chikako Ishikawa, Toshiya Komatsu
A number of (Z)-4-arylmethylene-1H-imidazol-5(4H)-ones, which are related to the fluorescent chromophore of the Aequorea green fluorescent protein (GFP), have been synthesized and evaluated their in vitro inhibitory activity against recombinant human aldose reductase for the first time. The GFP chromophore model 1a, with a p-hydroxy group on the 4-benzylidene and a carboxymethyl group on the N1 position, exhibited strong bioactivity with an IC50 value of 0.36 μM. This efficacy is higher than that of sorbinil, a known highly potent aldose reductase inhibitor...
October 8, 2016: European Journal of Medicinal Chemistry
Alan F Cowman, Julie Healer, Danushka Marapana, Kevin Marsh
Malaria has been a major global health problem of humans through history and is a leading cause of death and disease across many tropical and subtropical countries. Over the last fifteen years renewed efforts at control have reduced the prevalence of malaria by over half, raising the prospect that elimination and perhaps eradication may be a long-term possibility. Achievement of this goal requires the development of new tools including novel antimalarial drugs and more efficacious vaccines as well as an increased understanding of the disease and biology of the parasite...
October 20, 2016: Cell
Boris Redko, Helena Tuchinsky, Tamar Segal, Dror Tobi, Galia Luboshits, Osnat Ashur-Fabian, Albert Pinhasov, Gabi Gerlitz, Gary Gellerman
The newly discovered short (9 amino acid) non-RGD S-S bridged cyclic peptide ALOS-4 (H-cycl(Cys-Ser-Ser-Ala-Gly-Ser-Leu-Phe-Cys)-OH), which binds to integrin αvβ3 is investigated as peptide carrier for targeted drug delivery against human metastatic melanoma. ALOS4 binds specifically the αvβ3 overexpressing human metastatic melanoma WM-266-4 cell line both in vitro and in ex vivo assays. Coupling ALOS4 to the topoisomerase I inhibitor Camptothecin (ALOS4-CPT) increases the cytotoxicity of CPT against human metastatic melanoma cells while reduces dramatically the cytotoxicity against non-cancerous cells as measured by the levels of γH2A...
October 19, 2016: Oncotarget
Pier Francesco Bassi
If we think about the launch date of Mitomycin C, we could think that this supplement is very much focused on history of Medicine, and, yes, Mitomycin certainly has been a main contributor to the history of Urology. However, it is even more striking to think that even after fifty years of its use by Urologists worlwide, Mitomycin C remains an absolute "Must". The simplicity of use, the efficacy and the tolerability of Mitomycin explain its established role. In fact, "long standing" does not mean "old". The new technologies, introduced progressively in the last decades, have fully confirmed the present and future role of this drug, that is well illustrated in the articles contained in this supplement...
October 4, 2016: Urologia
Stacey Bagby, Wells A Messersmith, Todd M Pitts, Anna Capasso, Marileila Varella-Garcia, Peter J Klauck, Jihye Kim, Aik-Choon Tan, S Gail Eckhardt, John J Tentler, John Arcaroli
Patient derived tumor xenograft (PDTX) models provide a necessary platform in facilitating anti-cancer drug development prior to human trials. Human tumor pieces are injected subcutaneously into athymic nude mice (immunocompromised, T cell deficient) to create a bank of tumors and subsequently are passaged into different generations of mice in order to maintain these tumors from patients. Importantly, cellular heterogeneity of the original tumor is closely emulated in this model, which provides a more clinically relevant model for evaluation of drug efficacy studies (single agent and combination), biomarker analysis, resistant pathways and cancer stem cell biology...
September 30, 2016: Journal of Visualized Experiments: JoVE
Khaled Sinjab, Nouf Zimmo, Guo-Hao Lin, Ming-Pang Chung, Lujain Shaikh, Hom-Lay Wang
BACKGROUND: The use of statins on adult chronic patients showed a positive effect on their periodontal status. However, The effect of locally delivered statins on periodontal treatment has not yet been systematically analyzed. Hence, the present systematic review and meta-analyses aimed to evaluate the efficacy of statins on treating localized periodontal intrabony defects. MATERIAL AND METHODS: An electronic search of 3 databases (1965-2016 March 1(st)), including PubMed, Embase, CINAHL, and a hand search of peer-reviewed journals for relevant articles were performed...
October 21, 2016: Journal of Periodontology
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