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Drug induced diseases

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https://www.readbyqxmd.com/read/29793000/effect-of-a-bisphosphonate-and-selective-estrogen-receptor-modulator-on-bone-remodeling-in-streptozotocin-induced-diabetes-and-ovariectomized-rat-model
#1
Young-Seok Lee, Rishab Gupta, Jeong-Taik Kwon, Dae-Chul Cho, Ye Jin Seo, Sung Young Seu, Eui Kyun Park, Inbo Han, Chi-Heon Kim, Joo-Kyung Sung, Kyoung-Tae Kim
BACKGROUND CONTEXT: Diabetes and menopause can cause severe osteoporosis. In general, menopause and diabetes can lead to an imbalance in bone turnover, which results in secondary osteoporosis. However, the efficacy of antiresorptive drugs against this form of osteoporosis has not been extensively evaluated. OBJECTIVE: The aim of this study was to determine the changes in vertebral bone remodeling when postmenopausal osteoporosis is accompanied by diabetes and the efficacy of bisphosphonates and selective estrogen-receptor modulators (SERMs) against these outcomes...
May 21, 2018: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/29792946/investigation-of-nonalcoholic-fatty-liver-disease-induced-drug-metabolism-by-comparative-global-toxicoproteomics
#2
Ann-Yae Na, Jung Jae Jo, Ok Kwang Kwon, Riya Shrestha, Piljoung Cho, Kyu Min Kim, Sung Hwan Ki, Tae Hee Lee, Tae Won Jeon, Tae Cheon Jeong, Sangkyu Lee
Non-alcoholic fatty liver disease (NAFLD) includes conditions such as steatosis, non-alcoholic steatohepatitis, and ultimately hepatocellular carcinoma. Although the pathology of NAFLD is well-established, NAFLD-induced drug metabolism mediated by cytochrome P450 (CYP) in the liver has remained largely unexplored. Therefore, we investigated NAFLD-induced drug metabolism mediated by CYP by quantitative toxicoproteomics analysis. After administration of a methionine-choline deficient (MCD) diet to induce development of NAFLD, tandem mass tags-based liquid chromatography-tandem mass spectrometry analysis was conducted to investigate the dynamics of hepatic proteins...
May 21, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29792851/collagen-induced-arthritis-in-dark-agouti-rats-as-a-model-for-study-of-immunological-sexual-dimorphisms-in-the-human-disease
#3
Mirjana Dimitrijević, Nevena Arsenović-Ranin, Biljana Bufan, Mirjana Nacka-Aleksić, Mirjana Lazarević Macanović, Petar Milovanović, Marija Đurić, Jelena Sopta, Gordana Leposavić
Collagen-induced arthritis (CIA) is a frequently used animal model of rheumatoid arthritis, human autoimmune disease that exhibits clear sex bias in incidence and clinical course. Female Dark Agouti rats immunized for CIA showed also greater incidence and higher arthritic score than their male counterparts. The study investigated sex differences in mechanisms controlling the primary immune responses in draining lymph nodes (dLNs), as a factor contributing to this dimorphism. The higher frequencies of CD4 + CD25 + Foxp3- cells, presumably activated effector T (Teff) cells, and IL-17+, IFN-γ + and IL-17 + IFN-γ + T cells were found in female comapared with male rat dLNs...
May 21, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29792714/docking-screens-for-dual-inhibitors-of-disparate-drug-targets-for-parkinson-s-disease
#4
Mariama Jaiteh, Alexey Zeifman, Marcus Saarinen, Per Svenningsson, José M Brea, Maria Isabel Loza, Jens Carlsson
Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrelated proteins relevant for Parkinson's disease. A library with 5.4 million molecules was docked to crystal structures of the A2A adenosine receptor (A2AAR) and monoamine oxidase B (MAO-B)...
May 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29792572/galnac-sirna-conjugates-leading-the-way-for-delivery-of-rnai-therapeutics
#5
Aaron D Springer, Steven F Dowdy
Short-interfering RNA (siRNA)-induced RNAi responses have great potential to treat a wide variety of human diseases from cancer to pandemic viral outbreaks to Parkinson's Disease. However, before siRNAs can become drugs, they must overcome a billion years of evolutionary defenses designed to keep invading RNAs on the outside cells from getting to the inside of cells. Not surprisingly, significant effort has been placed in developing a wide array of delivery technologies. Foremost of these has been the development of N-acetylgalactosamine (GalNAc) siRNA conjugates for delivery to liver...
May 24, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29792126/neuropathological-profile-of-the-pentylenetetrazol-ptz-kindling-model
#6
E Samokhina, Alexander Samokhin
Epilepsy is a complex neurological disease characterized by spontaneous episodes of abnormal, simultaneous firing of a neuronal population and disturbances of consciousness (so-called seizures) of unknown cause. Antiepileptic drugs are only symptomatic treatment, and there is a strong demand for the search of an alternative treatment of epilepsy. For this purpose, animal models of epilepsy are an important prerequisite. There are various animal models with chronic brain dysfunctions thought to reflect the processes underlying human epilepsy...
May 23, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29791472/pioglitazone-abolishes-autistic-like-behaviors-via-the-il-6-pathway
#7
Thiago Berti Kirsten, Renato C Casarin, Maria M Bernardi, Luciano F Felicio
Autism is characterized by social deficits, communication abnormalities, and repetitive behaviors. The risk factors appear to include genetic and environmental conditions, such as prenatal infections and maternal dietary factors. Previous investigations by our group have demonstrated that prenatal exposure to lipopolysaccharide (LPS), which mimics infections by gram-negative bacteria, induces autistic-like behaviors. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism...
2018: PloS One
https://www.readbyqxmd.com/read/29791174/-drug-and-herbal-hepatotoxicity-an-overview-of-clinical-classifications
#8
Mária Szántová, Jozef Sedlačko, Martina Jakabovičová
Drug induced liver injury (DILI) is often underdiagnosed disease with increasing incidence. In developed countries it belongs to the leading causes of acute liver failure. Risk groups are women and persons older than 60 years. The work summarizes the up to date information on diagnosis and mostly used classifications on DILI. It is quite often and serious complication of medicament therapy. DILI belongs to the most often cause of acute hepatic failure in the old age in developed countries. Diagnostic procedure includes medical history (time correlation with drug intake), clinical symptoms and blood tests...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29790948/cardioprotection-induced-by-activation-of-gper-in-ovariectomized-rats-with-pulmonary-hypertension
#9
Allan K N Alencar, Guilherme C Montes, Daniele G Costa, Luiza V P Mendes, Ananssa M S Silva, Sabrina T Martinez, Margarete M Trachez, Valéria do M N Cunha, Tadeu L Montagnoli, Aline G M Fraga, Hao Wang, Leanne Groban, Carlos A M Fraga, Roberto T Sudo, Gisele Zapata-Sudo
Pulmonary hypertension (PH) is a disease of women (female-to-male ratio 4:1), and is associated with cardiac and skeletal muscle dysfunction. Herein, the activation of a new estrogen receptor (GPER) by the agonist G1 was evaluated in oophorectomized rats with monocrotaline (MCT)-induced PH. Depletion of estrogen was induced by bilateral oophorectomy (OVX) in Wistar rats. Experimental groups included SHAM or OVX rats that received a single intraperitoneal injection of MCT (60 mg/kg) for PH induction. Animals received s...
May 21, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29790165/igg1-b-cell-immunity-predates-ige-responses-in-epicutaneous-sensitization-to-foods
#10
Rodrigo Jiménez-Saiz, Yosef Ellenbogen, Joshua Koenig, Melissa E Gordon, Tina D Walker, Domenico Rosace, Paul Spill, Kelly Bruton, Joshua Kong, Kristin Monteiro, Jianping Wen, Elaine I Tuomanen, Roland Kolbeck, Derek K Chu, Susan Waserman, Manel Jordana
BACKGROUND: The generation of IgE-mediated food allergy in humans is silent, and only diagnosed upon manifestation of clinical symptoms. While experimental models have been used to investigate some mechanisms of allergic sensitization, the generation of humoral immunity and memory remain to be elucidated. Here, we defined the evolution of allergen-specific B cell responses during epicutaneous sensitization to foods. METHODS: Wild-type and genetic knockout animals, and drug or antibody strategies for cell depletion and immunoglobulin signaling blockade were used to investigate epicutaneous sensitization and disease progression; we analyzed allergen-specific germinal centers and IgG1+ memory B cells by flow cytometry, evaluated humoral responses and determined clinical reactivity (anaphylaxis)...
May 22, 2018: Allergy
https://www.readbyqxmd.com/read/29789603/vorinostat-and-quinacrine-have-synergistic-effects-in-t-cell-acute-lymphoblastic-leukemia-through-reactive-oxygen-species-increase-and-mitophagy-inhibition
#11
Bo Jing, Jin Jin, Rufang Xiang, Meng Liu, Li Yang, Yin Tong, Xinhua Xiao, Hu Lei, Wei Liu, Hanzhang Xu, Jiong Deng, Li Zhou, Yingli Wu
Despite recent progress in the treatment, the outcome of adult acute T-cell lymphoblastic leukemia (T-ALL) is poor. Development of novel approach to combat this disease is urgently required. Vorinostat, a pan-histone deacetylase (HDAC) inhibitor, exerts promising anticancer activity in a variety of solid and hematologic malignancies. However, the efficacy of vorinostat monotherapy is unsatisfactory. Here, we show that quinacrine (QC), an anti-malaria drug with potent autophagy inhibitory activity, could synergistically enhance vorinostat-induced cell death at a non-toxic concentration...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789558/celastrol-alleviates-renal-fibrosis-by-upregulating-cannabinoid-receptor-2-expression
#12
Ming Tang, Xu Cao, Kun Zhang, You Li, Quan-You Zheng, Gui-Qing Li, Qian-Hui He, Shu-Jing Li, Gui-Lian Xu, Ke-Qin Zhang
Renal fibrosis is the final manifestation of various chronic kidney diseases, and no effective therapy is available to prevent or reverse it. Celastrol, a triterpene that derived from traditional Chinese medicine, is a known potent anti-fibrotic agent. However, the underlying mechanisms of action of celastrol on renal fibrosis remain unknown. In this study, we found that celastrol treatment remarkably attenuated unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis. This was evidenced by the significant reduction in tubular injury; collagen deposition; accumulation of fibronectin, collagen I, and α-smooth muscle actin; and the expression levels of pro-fibrotic factors Vim, Cola1, and TGF-β1 mRNA, as well as inflammatory responses...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789506/design-and-efficacy-of-nanogels-formulations-for-intranasal-administration
#13
REVIEW
Blessing A Aderibigbe, Tobeka Naki
Nanogels are drug delivery systems that can bypass the blood-brain barrier and deliver drugs to the desired site when administered intranasally. They have been used as a drug delivery platform for the management of brain diseases such as Alzheimer disease, migraine, schizophrenia and depression. nanogels have also been developed as vaccine carriers for the protection of bacterial infections such as influenza, meningitis, pneumonia and as veterinary vaccine carriers for the protection of animals from encephalomyelitis and mouth to foot disease...
May 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29789401/treatment-with-eucalyptol-mitigates-cigarette-smoke-induced-lung-injury-through-suppressing-icam-1-gene-expression
#14
Na Yu, Yi-Tian Sun, Xin-Ming Su, Miao He, Bing Dai, Jian Kang
Objectives : This study was conducted to investigate of the clinical significance of Eucalyptol in treating cigarette smoke-induced lung injury with the potential mechanism involved in the event. Methods : Rats were exposed to air (control) and cigarette smoke (smoking) after they were treated with Eucalyptol (260mg/kg) orally once a day for 12 weeks. Cell counts of bronchoalveolar lavage fluid (BALF), measurements of mean liner intercept (MLI) and mean alveolar number (MAN) and lung function test were executed in experimental animals...
May 22, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29789102/an-update-on-drug-induced-oral-reactions
#15
Hila Yousefi, Mohammas Abdollahi
Adverse drug reactions (ADRs) are one of the major culprits in the development of oral lesions, which can be misdiagnosed with underlying diseases. The goal of this study is to summarize and update the current knowledge about drug-induced oral reactions. Electronic searches were performed in Scopus, Google Scholar, Cochrane and PubMed databases, for articles published between January 2008 and August 2017. Two authors screened the titles and abstracts for eligibility. Finally, 56 studies included in this review...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29788997/2d-versus-3d-human-induced-pluripotent-stem-cell-derived-cultures-for-neurodegenerative-disease-modelling
#16
REVIEW
Eduarda G Z Centeno, Helena Cimarosti, Angela Bithell
Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results...
May 22, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29788877/contribution-of-nrf2-in-gastrointestinal-protection-from-oxidative-injury
#17
Akinori Yanaka
The human gastrointestinal tract is exposed to a variety of toxic agents, such as Helicobacter pylori (H.pylori), nonsteroidal anti-inflammatory drugs (NSAIDs), gastric acid, enteric pathogenic bacteria, excessive auto immune reactions, and chronic mental stresses. These stressors generate free radicals within the gastrointestinal tissues, causing chronic inflammatory diseases, ulcers, cancers, and functional disturbances. Recent studies have demonstrated that some natural food compounds upregulate the nuclear factor erythroid 2-related factor 2-mediated antioxidant system, ameliorating or preventing these disorders...
May 21, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29788155/phase-i-study-of-the-checkpoint-kinase-1-inhibitor-gdc-0575-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#18
A Italiano, J R Infante, G I Shapiro, K N Moore, P M LoRusso, E Hamilton, S Cousin, M Toulmonde, S Postel-Vinay, S Tolaney, E M Blackwood, S Mahrus, F V Peale, X Lu, A Moein, J Epler, K DuPree, M Tagen, E R Murray, J L Schutzman, J O Lauchle, A Hollebecque, J-C Soria
Background: Checkpoint kinase 1 (Chk1) inhibition following chemotherapy-elicited DNA damage overrides cell cycle arrest and induces mitotic catastrophe and cell death. GDC-0575 is a highly-selective oral small-molecule Chk1 inhibitor that results in tumor shrinkage and growth delay in xenograft models. We evaluated the safety, tolerability, and pharmacokinetic properties of GDC-0575 alone and in combination with gemcitabine. Antitumor activity and Chk1 pathway modulation were assessed...
February 23, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29787319/usefulness-of-multiple-electrode-aggregometry-as-a-screening-tool-for-bleeding-disorders-in-a-pediatric-hospital
#19
Thorsten Haas, Melissa M Cushing, Stephanie Varga, Séverine Gilloz, Markus Schmugge
Platelet function testing is a cornerstone in the diagnostic investigation of patients with a bleeding history. Multiple electrode aggregometry (MEA) has been shown to detect von Willebrand disease (VWD), platelet function disorders, and drug-induced bleeding disorders. However, there are few studies supporting its successful use in children. We have implemented and used MEA over 3 years in our hemostasis laboratory in order to study its usefulness to supplement and expedite diagnosis. This is a retrospective, single-center, cohort study of 109 hospitalized children who underwent a laboratory investigation of hemostasis and either had a reported bleeding history or an abnormal bleeding episode...
May 22, 2018: Platelets
https://www.readbyqxmd.com/read/29787277/targeting-of-egfr-vegfr2-and-akt-by-engineered-dual-drug-encapsulated-mesoporous-silica-gold-nanoclusters-sensitizes-tamoxifen-resistant-breast-cancer
#20
Bn Prashanth Kumar, Nagaprasad Puvvada, Shashi Rajput, Siddik Sarkar, Madhusudan Kr Mahto, Murali M Yallapu, Amita Pathak, Luni Emdad, Swadesh K Das, Rui L Reis, Subhas C Kundu, Paul B Fisher, Mahitosh Mandal
Tamoxifen has improved overall disease-free survival and reduced mortality rates in cancer patients. However, breast cancer patients often fail to respond to tamoxifen therapy due to the development of a drug-resistant phenotype. Functional analysis and molecular studies suggest that protein mutation and dysregulation of survival signaling molecules such as epidermal growth factor receptor, vascular endothelial growth factor receptor 2 and Akt contribute to tamoxifen resistance. Various strategies, including combinatorial therapies, show to chemo-sensitize tamoxifen-resistant cancers...
May 22, 2018: Molecular Pharmaceutics
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