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Drug induced diseases

Hiroshi Kaji
Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner...
September 15, 2016: Comprehensive Physiology
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
Michael Christensen, Jonas B Jensen, Steen Jakobsen, Niels Jessen, Jørgen Frøkiær, Bruce E Kemp, Allison L Marciszyn, Hui Li, Núria M Pastor-Soler, Kenneth R Hallows, Rikke Nørregaard
The type-2 diabetes drug metformin has proven to have protective effects in several renal disease models. Here, we investigated the protective effects in a 3-day unilateral ureteral obstruction (3dUUO) mouse model. Compared with controls, ureteral obstructed animals displayed increased tubular damage and inflammation. Metformin treatment attenuated inflammation, increased the anti-oxidative response and decreased tubular damage. Hepatic metformin uptake depends on the expression of organic cation transporters (OCTs)...
October 26, 2016: Scientific Reports
Ehsan Malek, Byung-Gyu Kim, James J Driscoll
While the clinical benefit of proteasome inhibitors (PIs) for multiple myeloma (MM) treatment remains unchallenged, dose-limiting toxicities and the inevitable emergence of drug resistance limit their long-term utility. Disease eradication is compromised by drug resistance that is either present de novo or therapy-induced, which accounts for the majority of tumor relapses and MM-related deaths. Non-coding RNAs (ncRNAs) are a broad class of RNA molecules, including long non-coding RNAs (lncRNAs), that do not encode proteins but play a major role in regulating the fundamental cellular processes that control cancer initiation, metastasis, and therapeutic resistance...
October 6, 2016: Genes
Bharat Bhusan Subudhi, Pratap Kumar Sahu
Oxidative stress in brain underlies the major neurological disorders including Alzheimer's disease (AD) and Parkinson's disease (PD). Peripherally, Angiotensin-II is a major effector of inflammation. Identification of its capacity to access brain during hypertension, as well as location of central rennin angiotensin system have led to its recognition as the major effector of oxidative stress in brain. Clinical uses of antioxidants to antagonize this oxidative stress have mostly failed. In this scenario, AT1 blockers have been investigated to prevent neurodegeneration...
October 24, 2016: Mini Reviews in Medicinal Chemistry
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
Alencar Kolinski Machado, Ana Cristina Andreazza, Tatiane Morgana da Silva, Aline Augusti Boligon, Vanusa do Nascimento, Gustavo Scola, Angela Duong, Francine Carla Cadoná, Euler Esteves Ribeiro, Ivana Beatrice Mânica da Cruz
Neuropsychiatric diseases, such as bipolar disorder (BD) and schizophrenia (SCZ), have a very complex pathophysiology. Several current studies describe an association between psychiatric illness and mitochondrial dysfunction and consequent cellular modifications, including lipid, protein, and DNA damage, caused by cellular oxidative stress. Euterpe oleracea (açaí) is a powerful antioxidant fruit. Açaí is an Amazonian palm fruit primarily found in the lowlands of the Amazonian rainforest, particularly in the floodplains of the Amazon River...
2016: Oxidative Medicine and Cellular Longevity
Cheong K C Kwong Chung, Francesca Ronchi, Markus B Geuking
Healthy host-microbial mutualism relies on compartmentalization and proper regulation of systemic and mucosal immune responses. Nevertheless, the systemic immune system is frequently exposed to bouts of bacteraemia, which can trigger systemic antimicrobial immune reactivity including CD4(+) T cells. Low level bacteraemia can occur when immune compartmentalization is compromised, for example in the presence of innate immune deficiency or following use of nonsteroidal anti-inflammatory drugs (NSAID). We generated an Escherichia coli strain expressing a defined T helper neo-epitope to study systemic antigen-specific antimicrobial CD4(+) T cells and their potential involvement in the pathogenicity of inflammatory bowel diseases (IBD)...
October 24, 2016: Immunology
M Rieck, A F Schumacher-Schuh, V Altmann, S M Callegari-Jacques, C R M Rieder, M H Hutz
Levodopa is the most used drug to treat motor symptoms in Parkinson's disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated...
October 25, 2016: Pharmacogenomics Journal
Gang Wang, Rui Cao, Yongzhi Wang, Guofeng Qian, Han C Dan, Wei Jiang, Lingao Ju, Min Wu, Yu Xiao, Xinghuan Wang
Simvastatin is currently one of the most common drugs for old patients with hyperlipidemia, hypercholesterolemia and atherosclerotic diseases by reducing cholesterol level and anti-lipid properties. Importantly, simvastatin has also been reported to have anti-tumor effect, but the underlying mechanism is largely unknown. We collected several human bladder samples and performed microarray. Data analysis suggested bladder cancer (BCa) was significantly associated with fatty acid/lipid metabolism via PPAR signalling pathway...
October 25, 2016: Scientific Reports
Inmaculada Doña, María Salas, James R Perkins, Esther Barrionuevo, Francesco Gaeta, Jose A Cornejo-García, Paloma Campo, Maria José Torres
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the leading causes of hypersensitivity reactions to drugs, and they are classified in two groups: those induced by non-specific immunological mechanisms (non-allergic or cross-intolerance (CI) reactions), or by specific immunological mechanisms (allergic or selective reactions (SR)). The pathogenesis of CI is associated with their pharmacological activity (COX-1 inhibition), with symptoms due to an imbalance in the arachidonic acid pathway, independently of their chemical structure...
September 28, 2016: Current Pharmaceutical Design
Verónica Pastor, Marta Cristina Antonelli, María Eugenia Pallarés
Substance use disorder (SUD) refers to the detrimental use of psychoactive substances and it is related to a cluster of behavioural, cognitive and physiological dysfunctions indicating that the individual continues using the substance despite significant substance-related problems. Although it is one of the most prevalent neuropsychiatric diseases affecting society worldwide, the mechanism underlying the vulnerability of certain individuals is not well understood yet. It is now widely accepted that, in addition to genetic factors, environmental adversities during critical stages of development of an organism could also be considered as risk factors that contribute to SUD...
October 24, 2016: Neurotoxicity Research
Kerry Anne Rambaran, Charles F Seifert
Drug-induced interstitial lung disease is a rare condition attributed to several medications, including antimicrobial agents such as amphotericin B, anti-inflammatory agents such as methotrexate, biologic agents such as bevacizumab, and cardiovascular agents and chemotherapeutic agents. We describe the case of a 73-year-old female who developed interstitial lung disease following chronic use of nitrofurantoin for a urinary tract infection (UTI). The patient was taking nitrofurantoin 100 mg capsules twice daily for approximately 3 years...
December 2016: Drug Saf Case Rep
Ai-Li Xu, Ming-Chun Jiang, Xiao-Han Chen, Wen-Fang Chen
Icariin is the major bioactive component of Epimedium and has been demonstrated to be a potential drug for age-related diseases. The present study was aimed to investigate the neuroprotective properties of icariin against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in MES23.5 cells and the possible mechanisms. MTT assay showed that treatment with MPP(+) attenuated the cell viability in a dose-dependent manner in MES23.5 cells. Icariin pretreatment resulted in an enhancement of survival. Immunocytochemistry analysis revealed that icariin treatment attenuated MPP(+)-induced loss of tyrosine hydroxylase (TH) positive cells...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Vellingiri Balachandar, Venkatesan Dhivya, Mohan Gomathi, Subramaniam Mohanadevi, Balasubramanian Venkatesh, Bharathi Geetha
Human induced pluripotent stem cells (hiPSCs) are pluripotent stem cells generated from somatic cells by the introduction of a combination of pluripotency-associated genes such as OCT4, SOX2, along with either KLF4 and c-MYC or NANOG and LIN28 via retroviral or lentiviral vectors. Most importantly, hiPSCs are similar to human embryonic stem cells (hESCs) functionally as they are pluripotent and can potentially differentiate into any desired cell type when provided with the appropriate cues, but do not have the ethical issues surrounding hESCs...
2016: Stem Cell Investigation
Jonathan G Stine, Jennifer Wang, Brian W Behm
Drug-induced liver injury is a rare but clinically important diagnosis. Vedolizumab is an α4β7 integrin inhibitor recently approved for use in patients with moderate-to-severe inflammatory bowel disease. Cases of hepatoxicity due to vedolizumab in the pre-marketing stage were rare, and all cases resolved upon drug withdrawal. We present here the first reported case of hepatotoxicity attributable to vedolizumab, which despite drug cessation persisted with chronic cholestatic liver injury.
September 28, 2016: Journal of Clinical and Translational Hepatology
S Moriguchi, T Ishizuka, Y Yabuki, N Shioda, Y Sasaki, H Tagashira, H Yawo, J Z Yeh, H Sakagami, T Narahashi, K Fukunaga
Here, we report a novel target of the drug memantine, ATP-sensitive K(+) (KATP) channels, potentially relevant to memory improvement. We confirmed that memantine antagonizes memory impairment in Alzheimer's model APP23 mice. Memantine increased CaMKII activity in the APP23 mouse hippocampus, and memantine-induced enhancement of hippocampal long-term potentiation (LTP) and CaMKII activity was totally abolished by treatment with pinacidil, a specific opener of KATP channels. Memantine also inhibited Kir6.1 and Kir6...
October 25, 2016: Molecular Psychiatry
Doc Mariano, D de Souza, D F Meinerz, J Allebrandt, A F de Bem, W Hassan, Oed Rodrigues, Jbt da Rocha
Acquired immunodeficiency syndrome (AIDS) is a worldwide disease characterized by impairments of immune function. AIDS can be associated with oxidative stress (OS) that can be linked to selenium (Se) deficiency. Se is fundamental for the synthesis of selenoproteins, such as glutathione peroxidase and thioredoxin reductase. These enzymes catalyze the decomposition of reactive oxygen species and contribute to maintain equilibrium in cell redox status. Literature data indicate that organoselenium compounds, such as ebselen and diphenyl diselenide, have antioxidant properties in vitro and in vivo models associated with OS...
October 24, 2016: Human & Experimental Toxicology
Julia Nicolau, Thierry Lequerré, Hélène Bacquet, Olivier Vittecoq
Recent progress in the management of rheumatoid arthritis (RA) is turning attention toward comorbidities, such as diabetes. The objectives of this review are to clarify the links between RA and diabetes and to assess potential effects of disease-modifying antirheumatic drugs (DMARDs) on diabetes. The increased insulin resistance seen in RA is closely linked to the systemic inflammation induced by certain proinflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin-6. The prevalence of type 2 diabetes is increased in patients with RA...
October 21, 2016: Joint, Bone, Spine: Revue du Rhumatisme
Daull Philippe, Feraille Laurence, Barabino Stefano, Cimbolini Nicolas, Antonelli Sophie, Mauro Virgine, Garrigue Jean-Sébastien
Dry eye disease (DED) is a complex, multifactorial pathology characterized by corneal epithelium lesions and inflammation. The aim of the present study was to evaluate the efficacy of a cationic emulsion of cyclosporine A (CsA) in a mouse model that mimics severe dry eye. Eight to 12-week-old female C57BL/6N mice with tail patches of scopolamine were housed in controlled environment chambers to induce dry eye. At day three, following dry eye confirmation by corneal fluorescein staining (CFS, score 0-15) and phenol red thread (PRT) lacrimation test, the mice (n = 10/gp) were either treated 3 times a day in both eyes with drug-free cationic emulsion, a 0...
October 21, 2016: Experimental Eye Research
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