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https://www.readbyqxmd.com/read/28793071/nonbioequivalent-prescription-drug-interchangeability-concerns-on-patient-safety-and-drug-market-dynamics-in-brazil
#1
Francisco José Roma Paumgartten, Ana Cecilia Amado Xavier de Oliveira
Since the enforcement of Generics Act (1999), three types of pharmaceutically equivalent products are marketed in Brazil: innovative reference (REF), "similar" (S) and generic (G) drugs. The S (brand name) and G (generic name) borrow from REF (brand name) clinical data on safety and efficacy and dosage regimen. G (but not S) is bioequivalent to and interchangeable with REF. Starting in 2003, Brazilian Sanitary Surveillance Agency (Anvisa) has required data on relative bioavailability tests (with REF) to approve (or renew registration of) S drugs...
August 2017: Ciência & Saúde Coletiva
https://www.readbyqxmd.com/read/28792497/history-of-antibiotic-adaptation-influences-microbial-evolutionary-dynamics-during-subsequent-treatment
#2
Phillip Yen, Jason A Papin
Antibiotic regimens often include the sequential changing of drugs to limit the development and evolution of resistance of bacterial pathogens. It remains unclear how history of adaptation to one antibiotic can influence the resistance profiles when bacteria subsequently adapt to a different antibiotic. Here, we experimentally evolved Pseudomonas aeruginosa to six 2-drug sequences. We observed drug order-specific effects, whereby adaptation to the first drug can limit the rate of subsequent adaptation to the second drug, adaptation to the second drug can restore susceptibility to the first drug, or final resistance levels depend on the order of the 2-drug sequence...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28755314/checkpoint-inhibitors-for-non-small-cell-lung-cancer-among-older-adults
#3
REVIEW
Rawad Elias, Joshua Morales, Carolyn Presley
Non-small cell lung cancer (NSCLC) is mostly a disease of older adults, with its incidence and mortality rates increasing exponentially after the age of 65 years. Immune checkpoint inhibitors (ICIs) have changed the scene of NSCLC treatment after a long and relatively stagnant period of standard treatment regimens. However, little is known about the specific impact of these agents in older adults for whom care is often complicated by a variety of syndromes. This underlines the importance of understanding the dynamics of new cancer treatments in an older patient population...
September 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28750647/high-level-of-hiv-1-drug-resistance-mutations-in-patients-with-unsuppressed-viral-loads-in-rural-northern-south-africa
#4
Elizabeth M Etta, Lufuno Mavhandu, Cecile Manhaeve, Keanan McGonigle, Patrick Jackson, David Rekosh, Marie-Louise Hammarskjold, Pascal O Bessong, Denis M Tebit
BACKGROUND: Combination antiretroviral therapy (cART) has significantly reduced HIV morbidity and mortality in both developed and developing countries. However, the sustainability of cART may be compromised by the emergence of viral drug resistance mutations (DRM) and the cellular persistence of proviruses carrying these DRM. This is potentially a more serious problem in resource limited settings. METHODS: DRM were evaluated in individuals with unsuppressed viral loads after first or multiple lines of cART at two sites in rural Limpopo, South Africa...
July 27, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28741627/chronic-exposure-to-methamphetamine-disrupts-reinforcement-based-decision-making-in-rats
#5
Stephanie M Groman, Katherine M Rich, Nathaniel J Smith, Daeyeol Lee, Jane R Taylor
The persistent use of psychostimulant drugs, despite the detrimental outcomes associated with continued drug use, may be due to disruptions in reinforcement-learning processes that enable behavior to remain flexible and goal-directed in dynamic environments. To identify the reinforcement-learning processes that are affected by chronic exposure to the psychostimulant methamphetamine (MA), the current study sought to use computational and biochemical analyses to characterize decision-making processes, assessed by probabilistic reversal learning, in rats before and after they were exposed to an escalating dose regimen of MA (or saline control)...
July 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28741098/regulation-of-paclitaxel-activity-by-microtubule-associated-proteins-in-cancer-chemotherapy
#6
REVIEW
Xingjuan Shi, Xiaoou Sun
Microtubules, highly dynamic components of the cytoskeleton, participate in diverse cellular activities such as mitosis, cell migration, and intracellular trafficking. Dysregulation of microtubule dynamics contributes to the development of serious diseases, including cancer. The dynamic properties and functions of microtubule network are regulated by microtubule-associated proteins. Paclitaxel, an anti-microtubule agent of the taxane family, has shown a success in clinical treatment of many cancer patients...
July 24, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28728262/-evaluation-of-efficacy-of-immunosuppressive-therapy-plus-recombinant-human-thrombopoietin-for-children-with-severe-aplastic-anemia
#7
K Zhou, C X Liu, Y Li, J P Li, H H Fan, L Zhang, L P Jing, G X Peng, L Ye, Y Li, L Song, X Zhao, W R Yang, Z J Wu, F Chen, F K Zhang
Objective: To evaluate the therapeutic efficacy and safety of immunosuppressive therapy (IST) combined with recombinant human thrombopoietin (rhTPO) for severe aplastic anemia (SAA) in pediatric patients. Method: A retrospective case-control study was conducted and the clinical data of 45 pediatric patients with de novo SAA admitted to the Anemia Diagnosis and Treatment Center of Chinese Academy of Medical Sciences & Blood Disease Hospital during the period from December 2009 to December 2014 were analyzed...
July 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28723656/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#8
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722694/early-life-vincristine-exposure-evokes-mechanical-pain-hypersensitivity-in-the-developing-rat
#9
Katie A Schappacher, Lauren Styczynski, Mark L Baccei
Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat...
May 30, 2017: Pain
https://www.readbyqxmd.com/read/28720897/a-predictive-mathematical-modeling-approach-for-the-study-of-doxorubicin-treatment-in-triple-negative-breast-cancer
#10
Matthew T McKenna, Jared A Weis, Stephanie L Barnes, Darren R Tyson, Michael I Miga, Vito Quaranta, Thomas E Yankeelov
Doxorubicin forms the basis of chemotherapy regimens for several malignancies, including triple negative breast cancer (TNBC). Here, we present a coupled experimental/modeling approach to establish an in vitro pharmacokinetic/pharmacodynamic model to describe how the concentration and duration of doxorubicin therapy shape subsequent cell population dynamics. This work features a series of longitudinal fluorescence microscopy experiments that characterize (1) doxorubicin uptake dynamics in a panel of TNBC cell lines, and (2) cell population response to doxorubicin over 30 days...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714461/predicting-the-dynamics-of-bacterial-growth-inhibition-by-ribosome-targeting-antibiotics
#11
Philip Greulich, Jakub Dolezal, Matthew Scott, Martin R Evans, Rosalind J Allen
Understanding how antibiotics inhibit bacteria can help to reduce antibiotic use and hence avoid antimicrobial resistance - yet few theoretical models exist for bacterial growth inhibition by a clinically relevant antibiotic treatment regimen. In particular, in the clinic, antibiotic treatment is time-dependent. Here, we use a theoretical model, previously applied to steady-state bacterial growth, to predict the dynamical response of a bacterial cell to a time-dependent dose of ribosome-targeting antibiotic...
July 17, 2017: Physical Biology
https://www.readbyqxmd.com/read/28703284/brentuximab-vedotin-in-cd30-cutaneous-lymphoma-how-do-we-treat-how-shall-we-treat-a-review-of-the-literature
#12
REVIEW
R Stranzenbach, E Dippel, M Schlaak, R Stadler
Brentuximab vedotin is an antibody-drug conjugate that brings the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. Some prior studies could demonstrate good efficacy in cutaneous lymphomas. The standard therapeutic scheme is 1.8mg/kg every 3 weeks. Background of this work is the fact that cutaneous lymphoma has a different pathophysiology, and a dynamic other than systemic lymphoma. The objectives of this review were to get an overview of the currently used therapeutic regimen, and to check whether dose reduction or modified time intervals could benefit in a similar activity with less toxicity...
July 13, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28701951/pharmacokinetic-pharmacodynamic-modeling-of-tulathromycin-against-pasteurella-multocida-in-a-porcine-tissue-cage-model
#13
Qiaoyi Zhou, Guijun Zhang, Qin Wang, Wenguang Liu, Yan Huang, Pengling Yu, Yanqin Li, Huanzhong Ding, Binghu Fang
Tulathromycin, a macrolide antibiotic, is used for the treatment of respiratory disease in cattle and swine. The aim of our study was to investigate the in vitro and ex vivo activities of tulathromycin in serum, (non-inflamed) transudate, and (inflamed) exudate against Pasteurella multocida in piglets. The pharmacokinetics properties of tulathromycin were studied for serum, transudate, and exudate using a tissue cage model. In vitro antibiotic susceptibility of P. multocida and dynamic time-kill curve experiments over eight tulathromycin concentrations were determined...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28679376/managing-expectations-cognitive-authority-and-experienced-control-in-complex-healthcare-processes
#14
Katherine J Hunt, Carl R May
BACKGROUND: Balancing the normative expectations of others (accountabilities) against the personal and distributed resources available to meet them (capacity) is a ubiquitous feature of social relations in many settings. This is an important problem in the management of long-term conditions, because of widespread problems of non-adherence to treatment regimens. Using long-term conditions as an example, we set out middle range theory of this balancing work. METHODS: A middle-range theory was constructed four stages...
July 5, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28678551/nano-encapsulated-metformin-curcumin-in-plga-peg-inhibits-synergistically-growth-and-htert-gene-expression-in-human-breast-cancer-cells
#15
Raana Farajzadeh, Younes Pilehvar-Soltanahmadi, Mehdi Dadashpour, Shahrzad Javidfar, Javid Lotfi-Attari, Hadi Sadeghzadeh, Vahid Shafiei-Irannejad, Nosratollah Zarghami
The study was aimed at investigating the synergistic inhibitory effect of unique combinational regimen of nanocapsulated Metformin (Met) and Curcumin (Cur) against T47D breast cancer cells. For this purpose, Met and Cur were co-encapsulated in PEGylated PLGA nanoparticles (NPs) and evaluated for their therapeutic efficacy. The morphology and dynamic light scattering (DLS) analyses were carried out to optimize the nanoformulations. Drug release study was performed using dialysis method and then the cytotoxic and inhibitory effect of individual and combined drugs on expression level of hTERT in T47D breast cell line were evaluated using MTT assay and qPCR, respectively...
July 5, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28657578/antioxidants-mediate-both-iron-homeostasis-and-oxidative-stress
#16
REVIEW
Mustapha Umar Imam, Shenshen Zhang, Jifei Ma, Hao Wang, Fudi Wang
Oxidative stress is a common denominator in the pathogenesis of many chronic diseases. Therefore, antioxidants are often used to protect cells and tissues and reverse oxidative damage. It is well known that iron metabolism underlies the dynamic interplay between oxidative stress and antioxidants in many pathophysiological processes. Both iron deficiency and iron overload can affect redox state, and these conditions can be restored to physiological conditions using iron supplementation and iron chelation, respectively...
June 28, 2017: Nutrients
https://www.readbyqxmd.com/read/28646013/doxorubicin-effect-on-myocardial-metabolism-as-a-pre-requisite-for-subsequent-development-of-cardiac-toxicity-a-translational-18-f-fdg-pet-ct-observation
#17
Matteo Bauckneht, Giulia Ferrarazzo, Francesco Fiz, Silvia Morbelli, Matteo Sarocchi, Fabio Pastorino, Alberto Ghidella, Elena Pomposelli, Maurizio Miglino, Pietro Ameri, Laura Emionite, Flavia Ticconi, Eleonora Arboscello, Ambra Buschiazzo, Elena Augusta Massimelli, Salvatore Fiordoro, Anna Borra, Vanessa Cossu, Annalisa Bozzano, Adalberto Ibatici, Mirco Ponzoni, Paolo Spallarossa, Andrea Gallamini, Paolo Bruzzi, Gianmario Sambuceti, Cecilia Marini
The present translational study aimed to verify whether serial (18)F-fluoro-deoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT), predicts doxorubicin cardiotoxicity. Methods: Fifteen athymic mice were treated with intravenous administration of saline (n = 5), doxorubicin 5 mg/Kg (n = 5) or doxorubicin 7.5 mg/Kg (n = 5) and submitted to dynamic microPET scan to estimate left ventricular glucose consumption (LV-MRGlu) before and after chemotherapy. Thereafter, we retrospectively identified 69 patients successfully treated with Adriamycin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) regimen for Hodgkin's Disease (HD) and submitted to four consecutive FDG-PET/CT scans...
June 23, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28627310/comparing-cluster-level-dynamic-treatment-regimens-using-sequential-multiple-assignment-randomized-trials-regression-estimation-and-sample-size-considerations
#18
Timothy NeCamp, Amy Kilbourne, Daniel Almirall
Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level dynamic treatment regimen, the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention, including aggregate measures of the individuals or patients that compose it. Cluster-randomized sequential multiple assignment randomized trials can be used to answer multiple open questions preventing scientists from developing high-quality cluster-level dynamic treatment regimens...
January 1, 2017: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/28622767/praziquantel-decreases-fecundity-in-schistosoma-mansoni-adult-worms-that-survive-treatment-evidence-from-a-laboratory-life-history-trade-offs-selection-study
#19
Poppy H L Lamberton, Christina L Faust, Joanne P Webster
BACKGROUND: Mass drug administration of praziquantel is the World Health Organization's endorsed control strategy for schistosomiasis. A decade of annual treatments across sub-Saharan Africa has resulted in significant reductions of infection prevalence and intensity levels, although 'hotspots' remain. Repeated drug treatments place strong selective pressures on parasites, which may affect life-history traits that impact transmission dynamics. Understanding drug treatment responses and the evolution of such traits can help inform on how to minimise the risk of drug resistance developing, maximise sustainable control programme success, and improve diagnostic protocols...
June 16, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28590268/ar-v7-liquid-biopsy-for-treatment-stratification-in-prostate-cancer-how-close-are-we
#20
Claire Fletcher
PURPOSE OF REVIEW: Recent clinical introduction of the novel antiandrogen, Enzalutamide (Enza), CYP17 inhibitor, Abiraterone (Abi), and the second-generation chemotherapeutic, Cabazitaxel, has increased survival of patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). However, de novo and acquired resistance rates are high. A liquid biopsy that can rapidly, sensitively and robustly identify which patients will respond to treatment in a minimally invasive manner is urgently required to permit switch to a potentially more efficacious drug regimen, thus increasing survival whilst avoiding debilitating side effects associated with unnecessary treatment...
September 2017: Current Opinion in Urology
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