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Frontiers in Pharmacology

Nadia F Nocera, M Catherine Lee, Lucy M De La Cruz, Cinthia Rosemblit, Brian J Czerniecki
The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy...
2016: Frontiers in Pharmacology
Teng-Fei Li, Nian Gong, Yong-Xiang Wang
Aconitines, including bulleyaconitine A, probably the most bioactive and abundant alkaloids in Aconitum plant, are a group of diester C19-diterpenoid alkaloids with one acetylester group attached to C8 of the diterpenoid skeleton and one benzoylester group to C14. Hydrolysis of both groups is involved in the processing of Aconitum, a traditional Chinese medicinal approach. We recently demonstrated that bulleyaconitine A produced anti-hypersensitivity, which was mediated by stimulation of spinal microglial dynorphin A expression...
2016: Frontiers in Pharmacology
Outi Laatikainen, Sami Sneck, Risto Bloigu, Minna Lahtinen, Timo Lauri, Miia Turpeinen
Adverse drug events (ADEs) are more likely to affect geriatric patients due to physiological changes occurring with aging. Even though this is an internationally recognized problem, similar research data in Finland is still lacking. The aim of this study was to determine the number of geriatric medication-related hospitalizations in the Finnish patient population and to discover the potential means of recognizing patients particularly at risk of ADEs. The study was conducted retrospectively from the 2014 emergency department patient records in Oulu University Hospital...
2016: Frontiers in Pharmacology
Ester Pagano, Raffaele Capasso, Fabiana Piscitelli, Barbara Romano, Olga A Parisi, Stefania Finizio, Anna Lauritano, Vincenzo Di Marzo, Angelo A Izzo, Francesca Borrelli
Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for "CBD botanical drug substance," on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil...
2016: Frontiers in Pharmacology
Salma Malik, Kapil Suchal, Jagriti Bhatia, Sana I Khan, Swati Vasisth, Ameesha Tomar, Sameer Goyal, Rajeev Kumar, Dharamvir S Arya, Shreesh K Ojha
Emblica officinalis Gaertn. belonging to family Euphorbiaceae is commonly known as Indian gooseberry or "Amla" in India. It is used as a 'rejuvenating herb' in traditional system of Indian medicine. It has been shown to possess antioxidant, anti-inflammatory and anti-apoptotic effects. Thus, on the basis of its biological effects, the present study was undertaken to evaluate the protective effect of the dried fruit extract of the E. Officinalis (EO) in cisplatin-induced nephrotoxicity in rats and also to evaluate the mechanism of its nephroprotection...
2016: Frontiers in Pharmacology
Ponnusamy Baskaran, Aloka Kumari, Bhekumthetho Ncube, Johannes Van Staden
Mondia whitei (Hook.f.) Skeels is an important endangered medicinal and commercial plant in South Africa. In vitro propagation systems are required for biomass production and bioactivity analysis to supplement wild resources/stocks. Adventitious roots from somatic embryogenic explants using suspension culture and ex vitro-grown plants produced via somatic embryogenesis were established using different plant growth regulator treatments. The adventitious root biomass and different parts of ex vitro-grown and mother plants were used to investigate the potential for acetylcholinesterase (AChE) and antibacterial activities...
2016: Frontiers in Pharmacology
José A S Crippa, Ana C S Crippa, Jaime E C Hallak, Rocio Martín-Santos, Antonio W Zuardi
Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time...
2016: Frontiers in Pharmacology
Toru Hosoi, Yuka Suyama, Takaaki Kayano, Koichiro Ozawa
Leptin resistance is one of the mechanisms involved in the pathophysiology of obesity. The present study showed that glucose deprivation inhibited leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) and signal transducer and activator of transcription 5 (STAT5) in neuronal cells. Flurbiprofen reversed glucose deprivation-mediated attenuation of STAT3, but not STAT5 activation, in leptin-treated cells. Glucose deprivation increased C/EBP-homologous protein and glucose regulated protein 78 induction, indicating the activation of unfolded protein responses (UPR)...
2016: Frontiers in Pharmacology
Gemma Amo, José A Cornejo-García, Jesus M García-Menaya, Concepcion Cordobes, M J Torres, Gara Esguevillas, Cristobalina Mayorga, Carmen Martinez, Natalia Blanca-Lopez, Gabriela Canto, Alfonso Ramos, Miguel Blanca, José A G Agúndez, Elena García-Martín
The high-affinity IgE receptor (Fcε RI) is a heterotetramer of three subunits: Fcε RIα, Fcε RIβ, and Fcε RIγ (αβγ2) encoded by three genes designated as FCER1A, FCER1B (MS4A2), and FCER1G, respectively. Recent evidence points to FCERI gene variability as a relevant factor in the risk of developing allergic diseases. Because Fcε RI plays a key role in the events downstream of the triggering factors in immunological response, we hypothesized that FCERI gene variants might be related with the risk of, or with the clinical response to, selective (IgE mediated) non-steroidal anti-inflammatory (NSAID) hypersensitivity...
2016: Frontiers in Pharmacology
Yu Yan, Xin Cheng, Ren-Hao Yang, He Li, Jian-Long Chen, Zheng-Lai Ma, Guang Wang, Manli Chuai, Xuesong Yang
Phenobarbital is an antiepileptic drug that is widely used to treat epilepsy in a clinical setting. However, a long term of phenobarbital administration in pregnant women may produce side effects on embryonic skeletogenesis. In this study, we aim to investigate the mechanism by which phenobarbital treatment induces developmental defects in long bones. We first determined that phenobarbital treatment decreased chondrogenesis and inhibited the proliferation of chondrocytes in chick embryos. Phenobarbital treatment also suppressed mineralization in both in vivo and in vitro long bone models...
2016: Frontiers in Pharmacology
Irina D Strazhesko, Olga N Tkacheva, Dariga U Akasheva, Ekaterina N Dudinskaya, Ekaterina V Plokhova, Valentina S Pykhtina, Anna S Kruglikova, Natalia V Kokshagina, Natalia V Sharashkina, Mikhail V Agaltsov, Daria A Kashtanova, Vladimir A Vygodin, Irina N Ozerova, Dmitry A Skvortsov, Daria Vasilkova, Sergey A Boytsov
Background: Telomerase activity (TA) is considered as the biomarker for cardiovascular aging and cardiovascular diseases (CVDs). Recent studies suggest a link between statins and telomere biology that may be explained by anti-inflammatory actions of statins and their positive effect on TA. Until now, this effect has not been investigated in prospective randomized studies. We hypothesized that 12 months of atorvastatin therapy increased TA in peripheral blood mononuclear cells. Methods: In a randomized, placebo-controlled study 100 hypercholesterolemic patients, aged 35-75 years, free of known CVDs and diabetes mellitus type 2 received 20 mg of atorvastatin daily or placebo for 12 months...
2016: Frontiers in Pharmacology
Tereza Touskova, Magda Vytrisalova, Vladimir Palicka, Tereza Hendrychova, Yang-Ti Chen, Leos Fuksa
Background: Osteoporosis is a chronic disease and adherence can fluctuate over time. Therefore, longer observation is necessary to investigate the stability of patients' adherence. The study aim was to compare the overall adherence (OA) to supplementation with the fixed combination of calcium and vitamin D (Ca/D) in postmenopausal women at baseline and after 1 year, and to evaluate the fluctuation of the OA in individual months. Furthermore, we studied whether adherence is influenced by signing of informed consent and routine medical check-up...
2016: Frontiers in Pharmacology
Shanaz Ghuman, Bhekumthetho Ncube, Jeffrey F Finnie, Lyndy J McGaw, Roger M Coopoosamy, Johannes Van Staden
Medicinal plants used for wound healing and skin diseases are the key to unlocking the doors to combating problematic skin diseases as resistance of pathogens to pharmaceuticals and allopathic management continues to increase. The study aimed at investigating the antimicrobial efficacies, phenolic content, and cytotoxicity effects of 11 medicinal plant extracts commonly used for treating skin conditions and wound healing in traditional medicine within KwaZulu-Natal. Eleven plant species were separated into different plant parts (bulbs, roots, leaves) and extracted with different solvents...
2016: Frontiers in Pharmacology
José E Belizário, Beatriz A Sangiuliano, Marcela Perez-Sosa, Jennifer M Neyra, Dayson F Moreira
With multiple omics strategies being applied to several cancer genomics projects, researchers have the opportunity to develop a rational planning of targeted cancer therapy. The investigation of such numerous and diverse pharmacogenomic datasets is a complex task. It requires biological knowledge and skills on a set of tools to accurately predict signaling network and clinical outcomes. Herein, we describe Web-based in silico approaches user friendly for exploring integrative studies on cancer biology and pharmacogenomics...
2016: Frontiers in Pharmacology
Jose A Garcia-Salcedo, Juan D Unciti-Broceta, Javier Valverde-Pozo, Miguel Soriano
Leishmania and Trypanosoma are members of the Trypanosomatidae family that cause severe human infections such as leishmaniasis, Chagas disease, and sleeping sickness affecting millions of people worldwide. Despite efforts to eradicate them, migrations are expanding these infections to developing countries. There are no vaccines available and current treatments depend only on chemotherapy. Drug resistance is a major obstacle for the treatment of these diseases given that existing drugs are old and limited, with some having severe side effects...
2016: Frontiers in Pharmacology
Ming Gu, Ping Zhao, Jinwen Huang, Yuanyuan Zhao, Yahui Wang, Yin Li, Yifei Li, Shengjie Fan, Yue-Ming Ma, Qingchun Tong, Li Yang, Guang Ji, Cheng Huang
Background and purpose: Silymarin, a standardized extract of the milk thistle seeds, has been widely used to treat chronic hepatitis, cirrhosis, and other types of toxic liver damage. Despite increasing studies on the action of silymarin and its major active constituent, silybin in their therapeutic properties against insulin resistance, diabetes and hyperlipidaemia in vitro and in vivo, the mechanism underlying silymarin action remains unclear. Experimental approach: C57BL/6 mice were fed high-fat diet (HFD) for 3 months to induce obesity, insulin resistance, hyperlipidaemia, and fatty liver...
2016: Frontiers in Pharmacology
Reham H Mekky, Mostafa R Fayed, Mohamed R El-Gindi, Azza R Abdel-Monem, María Del Mar Contreras, Antonio Segura-Carretero, Essam Abdel-Sattar
Chickpea (Cicer arietinum) is a legume of the family Fabaceae, subfamily Faboideae. In Egypt, chickpea seeds are usually consumed at raw green and tender stage, or in the form of mature dry seeds. In our previous study, 'Giza 1' seeds exhibited stronger antioxidant activity and higher total phenol content than those from other Egyptian cultivars. In order to assess the biological potential of 'Giza 1' seeds in vivo, the extraction procedure was reproduced here. The extract was standardized using liquid chromatography coupled to diode array detector and tandem mass spectrometry (MS/MS) to evaluate their hepatoprotective effect on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats and acute toxicity...
2016: Frontiers in Pharmacology
Fernanda F Peres, Raquel Levin, Mayra A Suiama, Mariana C Diana, Douglas A Gouvêa, Valéria Almeida, Camila M Santos, Lisandro Lungato, Antônio W Zuardi, Jaime E C Hallak, José A Crippa, D'Almeida Vânia, Regina H Silva, Vanessa C Abílio
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson's disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson's disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats...
2016: Frontiers in Pharmacology
Carmine D'Aniello, Maria G Vitale, Azzurra Farnesi, Lorenzo Calvetti, Maria M Laterza, Carla Cavaliere, Chiara Della Pepa, Vincenza Conteduca, Anna Crispo, Ferdinando De Vita, Francesco Grillone, Enrico Ricevuto, Michele De Tursi, Rocco De Vivo, Marilena Di Napoli, Sabrina C Cecere, Gelsomina Iovane, Alfonso Amore, Raffaele Piscitelli, Giuseppe Quarto, Salvatore Pisconti, Gennaro Ciliberto, Piera Maiolino, Paolo Muto, Sisto Perdonà, Massimiliano Berretta, Emanuele Naglieri, Luca Galli, Giacomo Cartenì, Ugo De Giorgi, Sandro Pignata, Gaetano Facchini, Sabrina Rossetti
Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib-axitinib sequence, were the primary endpoint...
2016: Frontiers in Pharmacology
Michael Ermisch, Anna Bucsics, Patricia Vella Bonanno, Francis Arickx, Alexander Bybau, Tomasz Bochenek, Marc van de Casteele, Eduardo Diogene, Jurij Fürst, Kristina Garuolienė, Martin van der Graaff, Jolanta Gulbinovič, Alan Haycox, Jan Jones, Roberta Joppi, Ott Laius, Irene Langner, Antony P Martin, Vanda Markovic-Pekovic, Laura McCullagh, Einar Magnusson, Ellen Nilsen, Gisbert Selke, Catherine Sermet, Steven Simoens, Robert Sauermann, Ad Schuurman, Ricardo Ramos, Vera Vlahovic-Palcevski, Corinne Zara, Brian Godman
Payers are a major stakeholder in any considerations and initiatives concerning adaptive licensing of new medicinal products, also referred to as Medicines Adaptive Pathways to patients (MAPPs). Firstly, the scope and necessity of MAPPs need further scrutiny, especially with regard to the definition of unmet need. Conditional approval pathways already exist for new medicines for seriously debilitating or life-threatening diseases and only a limited number of new medicines are innovative. Secondly, MAPPs will result in new medicines on the market with limited evidence about their effectiveness and safety...
2016: Frontiers in Pharmacology
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