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Drug Treatment Review

Peter Sandner, Peter Berger, Christoph Zenzmaier
Fibrotic diseases cause high rates of morbidity and mortality, and their incidence increases with age. Despite intense research and development efforts, effective and well-tolerated antifibrotic treatments are scarce. Transforming growth factor-β signaling, which is widely considered the most important profibrotic factor, causes a pro-oxidant shift in redox homeostasis and a concomitant decrease in nitric oxide (NO) signaling. The NO/cyclic guanosine monophosphate (cGMP) signaling cascade plays a pivotal role in the regulation of cell and organ function in whole-body hemostasis...
October 27, 2016: Gerontology
Nilesh Chande, Cassandra M Townsend, Claire E Parker, John K MacDonald
BACKGROUND: The results from controlled clinical trials investigating the efficacy of azathioprine and 6-mercaptopurine for the treatment of active Crohn's disease have been conflicting and controversial. An updated meta-analysis was performed to assess the effectiveness of these drugs for the induction of remission in active Crohn's disease. OBJECTIVES: The primary objective was to determine the efficacy and safety of azathioprine and 6-mercaptopurine for induction of remission in active Crohn's disease...
October 26, 2016: Cochrane Database of Systematic Reviews
Athumani M Ramadhani, Tamsyn Derrick, David Macleod, Martin J Holland, Matthew J Burton
BACKGROUND: Trachoma is a blinding disease, initiated in early childhood by repeated conjunctival infection with the obligate intracellular bacterium Chlamydia trachomatis. The population prevalence of the clinical signs of active trachoma; ''follicular conjunctivitis" (TF) and/or ''intense papillary inflammation" (TI), guide programmatic decisions regarding the initiation and cessation of mass drug administration (MDA). However, the persistence of TF following resolution of infection at both the individual and population level raises concerns over the suitability of this clinical sign as a marker for C...
October 2016: PLoS Neglected Tropical Diseases
Jason Shafrin, Taylor T Schwartz, Darius N Lakdawalla, Felicia M Forma
BACKGROUND: Nonadherence to antipsychotic medication among patients with schizophrenia results in poor symptom management and increased health care and other costs. Despite its health impact, medication adherence remains difficult to accurately assess. New technologies offer the possibility of real-time patient monitoring data on adherence, which may in turn improve clinical decision making. However, the economic benefit of accurate patient drug adherence information (PDAI) has yet to be evaluated...
November 2016: Journal of Managed Care & Specialty Pharmacy
Claudiu T Supuran
The enzyme carbonic anhydrase (CA, EC is found in numerous organisms across the tree of life, with seven distinct classes known to date. CA inhibition can be exploited for the treatment of edema, glaucoma, seizures, obesity, cancer and infectious diseases. A myriad of CA inhibitor (CAI) classes and inhibition mechanisms have been identified over the past decade, mainly through structure-based drug design approaches. Five different CA inhibition mechanisms are presently known. Areas covered: Recent advances in structure-based CAI design are reviewed, with periodic table-based organization of inhibitor classes...
October 26, 2016: Expert Opinion on Drug Discovery
Rama I Mahran, Magda M Hagras, Duxin Sun, Dean E Brenner
Cancer is still a major cause of death all over the world. Its incidence and prevalence are increasing drastically. Cancer treatment imposes high socioeconomic burden with little impact especially on aggressive types of cancer. Reversing or delaying carcinogenesis "cancer chemoprevention" by purified or extracted natural products is a cost-effective alternative. Curcumin is widely available, inexpensive spice that has been used in ancient folk medicine for millennia, especially in India. Curcumin has the pharmacological properties that slow or reverse cellular proliferation and enhance apoptosis and differentiation associated with a diverse array of molecular effects...
October 25, 2016: AAPS Journal
Michela Bulfoni, Matteo Turetta, Fabio Del Ben, Carla Di Loreto, Antonio Paolo Beltrami, Daniela Cesselli
Although the enumeration of circulating tumor cells (CTC) defined as expressing both epithelial cell adhesion molecule and cytokeratins (EpCAM⁺/CK⁺) can predict prognosis and response to therapy in metastatic breast, colon and prostate cancer, its clinical utility (i.e., the ability to improve patient outcome by guiding therapy) has not yet been proven in clinical trials. Therefore, scientists are now focusing on the molecular characterization of CTC as a way to explore its possible use as a "surrogate" of tumor tissues to non-invasively assess the genomic landscape of the cancer and its evolution during treatment...
October 24, 2016: International Journal of Molecular Sciences
Fernando Pastor
The renaissance of cancer immunotherapy is, nowadays, a reality. In the near future, it will be very likely among the first-line treatments for cancer patients. There are several different approaches to modulate the immune system to fight against tumor maladies but, so far, monoclonal antibodies may currently be the most successful immuno-tools used to that end. The number of ongoing clinical trials with monoclonal antibodies has been increasing exponentially over the last few years upon the Food and Drug Administration (FDA) approval of the first immune-checkpoint blockade antibodies...
October 24, 2016: Pharmaceuticals
Milena Masullo, Cosimo Pizza, Sonia Piacente
Oleanolic acid has been considered a good start molecule for synthetic exploitation. Thus hundreds of oleanane triterpenoids have been synthesized and patented. Also many oleanane saponins have been patented for their biological activities and possible pharmaceutical use. Areas covered: Patents reporting the biological activities of oleanane derivatives and saponins with oleanane-type aglycones were examined. Among the synthesized oleanane derivatives, the most promising seem to be 2-cyano-3,12-dioxoolean-1,9(11)-dien-28-oic acid derivatives which interfere with many pathways involved in inflammation, oxidative stress and cell proliferation...
October 26, 2016: Expert Opinion on Therapeutic Patents
Ki-Young Lee, Bong-Jin Lee
Bacterial toxin-antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins...
October 22, 2016: Toxins
Rita Turnaturi, Giuseppina Aricò, Giuseppe Ronsisvalle, Lorella Pasquinucci, Carmela Parenti
Polypharmacology, or the associations between two or more drugs producing biological effects on two or more different sites of action could represent a possible therapeutic approach for the clinical management of acute and chronic pain. The multitude and complexity of neuronal mechanisms that contribute to pain transmission provide several possible targets for pharmacological intervention. Thus, multitarget ligands possessing opioid-opioid or non-opioid-opioid mechanisms of action are potential drug candidates for pain relief...
October 24, 2016: Current Medicinal Chemistry
Philipp Sebastian Reif, Meng-Han Tsai, Ingo Helbig, Felix Rosenow, Karl Martin Klein
Therapy with current antiepileptic drugs aims at reducing the likelihood of seizure occurrence rather than influencing the underlying disease process. Therefore, antiepileptic drugs have an anticonvulsant rather than antiepileptic property. Areas covered: The increasing identification of genetic causes for epilepsy over the recent years improves the understanding of the underlying epileptogenic process and allows for the possibility of directed therapeutic approaches. An ideal antiepileptic therapy consists of a drug which is able to influence the functional changes caused by a specific pathogenic variant...
October 26, 2016: Expert Review of Neurotherapeutics
Theodora Karamanidou, Vassilis Bourganis, Olga Kammona, Costas Kiparissides
Biopharmaceutics have been recognized as the drugs of choice for the treatment of several diseases, mainly due to their high selectivity and potent action. Nonetheless, their oral administration is a rather challenging problem, since their bioavailability is significantly hindered by various physiological barriers along the GI tract, including their acid-induced hydrolysis in the stomach, their enzymatic degradation throughout the GI tract and their poor mucosa permeability. Lipid-based nanocarriers represent a viable means for enhancing the oral bioavailability of biomolecules while diminishing toxicity-related issues...
October 26, 2016: Nanomedicine
Rui Feng, Xiaotian Zhang, Sheng Yang
With the deeper research of the proliferation, invasion and metastasis mechanisms of the gastric cancer, targeted therapy has become a hot spot in this field. The exploration of targeted agents for gastric cancer is mainly concentrated upon the drugs that target human epidermal growth factor receptor (HER) family, the vascular endothelial growth factor (VEGF), the phosphatidylinositol 3-kinase-protein kinase/mammalian target of rapamycin (PI3K/mTOR) and the NF-κB signaling pathways. The targeted drugs relevant to HER family include the Cetuximab, Nimotuzumab, Matuzumab, Panitumumab and Erlotinib which are aimed at HER-1, the Trastuzumab, Pertuzumab and T-DM1 (trastuzumab emtansine) which are aimed at HER-2, and the Lapatinib and Afatinib which are the multi-target agents of HER...
October 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Cristina Solomon, Wolfgang Korte, Dietmar Fries, Inna Pendrak, Christine Joch, Albrecht Gröner, Ingvild Birschmann
BACKGROUND: Plasma-derived factor XIII (FXIII) concentrate is an effective treatment for FXIII deficiency. We describe adverse drug reactions (ADRs) reported during pharmacovigilance monitoring of Fibrogammin®/Corifact® and review published safety data. METHODS: Postmarketing safety reports recorded by CSL Behring from June 1993 to September 2013 were analyzed. Clinical studies published during the same period were also reviewed. RESULTS: Commercial data indicated that 1,653,450,333 IU FXIII concentrate were distributed over the review period, equivalent to 1,181,036 doses for a 70 kg patient...
September 2016: Transfusion Medicine and Hemotherapy
Frank Loganzo, Matthew Sung, Hans-Peter Gerber
Drug resistance limits the effectiveness of cancer therapies. Despite attempts to develop curative anticancer treatments, tumors evolve evasive mechanisms limiting durable responses. Hence, diverse therapies are used to attack cancer, including cytotoxic and targeted agents. Antibody-drug conjugates (ADC) are biotherapeutics designed to deliver potent cytotoxins to cancer cells via tumor-specific antigens. Little is known about the clinical manifestations of drug resistance to this class of therapy; however, recent preclinical studies reveal potential mechanisms of resistance...
October 25, 2016: Molecular Cancer Therapeutics
Tristan Struja, Hannah Fehlberg, Alexander Kutz, Larissa Guebelin, Christian Degen, Beat Muller, Philipp Schuetz
BACKGROUND: Identification of pre-treatment risk factors predicting relapse in patients with hyperthyroidism of Graves' disease after stopping anti-thyroid drugs [ATD] is decisive to guide therapeutic options. PURPOSE: We performed a systematic search and meta-analysis to study predictors for relapse after stopping ATD in patients with Graves' disease. METHODS: Based on a pre-specified protocol, we searched PubMed, EMBASE and Cochrane in July 2015 for case-control, controlled, and randomized-controlled trials reporting risk factors for relapse after stopping ATD...
October 25, 2016: European Journal of Endocrinology
Chul Kim, Chuong D Hoang, Aparna H Kesarwala, David S Schrump, Udayan Guha, Arun Rajan
Due to an improved understanding of lung cancer biology and improvement in systemic treatment, an "oligometastatic" state where metastatic disease is present at a limited number of anatomic sites is being increasingly recognized. An "oligoprogressive" state, a similar but distinct entity, refers to disease progression at a limited number of anatomic sites with continued response or stable disease at other sites of disease. Such an oligoprogressive state is best described in patients with non-small-cell lung cancer (NSCLC) treated with molecular targeted therapy...
October 22, 2016: Journal of Thoracic Oncology
Jeffrey S Borer, Prakash C Deedwania, Jae B Kim, Michael Böhm
Heart rate (HR) is a risk factor in patients with chronic systolic heart failure (HF) that, when reduced, provides outcome benefits. It is also a target for angina pectoris prevention and a risk marker in chronic coronary artery disease without HF. HR can be reduced by drugs; however, among those used clinically, only ivabradine reduces HR directly in the sinoatrial nodal cells without other known effects on the cardiovascular system. This review provides current information regarding the safety and efficacy of HR reduction with ivabradine in clinical studies involving >36,000 patients with chronic stable coronary artery disease and >6,500 patients with systolic HF...
September 15, 2016: American Journal of Cardiology
Amanda C Capino, Jamie L Miller, Peter N Johnson
The need for sedation and analgesia and treatment of iatrogenic drug withdrawal is common in critically ill children. First-line therapy typically includes opioid agonists. However, clonidine, a central alpha2 agonist, has been suggested as a treatment option for sedation and analgesia and iatrogenic drug withdrawal. Therefore, we conducted a literature search to identify articles evaluating the use of enteral and transdermal clonidine in critically ill infants and children for sedation and analgesia and treatment of iatrogenic drug withdrawal...
October 25, 2016: Pharmacotherapy
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