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Disease modifying drugs

Javier Narváez, Pablo Juarez López, Judit LLuch, José Antonio Narváez, Ramón Palmero, Xavier García Del Muro, Joan Miquel Nolla, Eva Domingo-Domenech
OBJECTIVE: To evaluate the prevalence and type of rheumatic immune-related adverse events (IRAEs) in patients receiving programmed cell death protein-1 (PD-1) inhibitors. METHODS: This is a single-center prospective observational study, including all cancer patients receiving PD-1 inhibitors between January 2016 and January 2018. RESULTS: During the period analyzed, we evaluated a total of 11 patients. No patient had pre-existing rheumatic or autoimmune disease...
August 10, 2018: Autoimmunity Reviews
Erika Sasaki
Rodent laboratory animals, such as mice and rats have been greatly contributing to biomedical research. Although its usefulness would not change in the future, nonhuman primates (NHPs) also offer excellent models for preclinical research to assess safety and efficacy of developing novel therapeutic approaches because of their similarities of genetics, metabolism and physiological characteristics to humans. Recent years, the gene modification technology in nonhuman primates has been developed. In fact, pre-clinical studies using nonhuman primates are increasing in the world, especially in the neuroscience research field...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Alexandre A de Castro, Elaine F F da Cunha, Ander F Pereira, Flavia V Soares, Daniel H S Leal, Kamil Kuca, Teodorico C Ramalho
Alzheimer's disease is known to be a chronic disease, with an estimated prevalence of about 10-30%, considering the population over 60 years of age. Most patients with this disorder (> 95%) present the sporadic form, being characterized by a late onset (80-90 years of age), and it is the consequence of the failure to clear the amyloid-β (Aβ) peptide from the interstices of the brain. Significant numbers of genetic risk factors for the sporadic disease have been researched. Some existing drugs for Alzheimer's disease provide symptomatic benefit for up to 12 months, but there are no approved disease-modifying therapies...
August 13, 2018: Current Alzheimer Research
Mahsa Moeinian, Hamed Sotoude, Zahra Mohebbi, Ali Asadollahi-Amin, Rambod Mozafari
Cyclosporine is one of the main drugs used for the prophylaxis of graft versus host disease in bone marrow transplanted patients. Hypersensitivity reaction to intravenous cyclosporine is rare and might be due to its vehicle polyoxyethylated castor oil, Cremophor EL. The exact mechanism is unknown, but IgE and IgG antibodies, complement, and histamine release have been considered to play a role in the development of this reaction. Here, we describe a case of anaphylaxis to intravenous cyclosporine, which was developed in a 19-year-old Iranian female with acute myeloid leukemia who underwent allogeneic bone marrow transplantation from her sister...
March 2018: Indian Journal of Pharmacology
Michał Szczypior, Marcin Matuszewski
Idiopathic overactive bladder due to its high impact on quality of life and high prevalence is a significant problem in everyday clinical practice. Currently, we do not have medicines that allow patients to be cured completely. Therapy is focused on the elimination or reduction of symptoms. An established position in the treatment of this disease for many years has a botulinum toxin. This therapy is used in patients whose conservative methods have not improved or are not acceptable because of side effects. The therapeutic effect after the injection of bladder detrusor muscle is limited in time and does not occur in all patients...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Igri Kolaj, S Imindu Liyanage, Donald F Weaver
Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by progressive dementia, neuroinflammation and the accumulation of intracellular neurofibrillary tangles and extracellular plaques. The etiology of AD is unclear, but is generally attributed to four leading hypotheses: (i) abnormal folding and aggregation of amyloid-β (Aβ)/tau proteins (ii) activation of the innate immune system, (iii) mitochondrial dysfunction, and (iv) oxidative stress. To date, therapeutic strategies have largely focused on Aβ-centric targets; however, the repeated failure of clinical trials and the continued lack of a disease-modifying therapy demand novel, multifaceted approaches...
August 8, 2018: Neurochemistry International
Christian Gisselbrecht, David Sibon
PURPOSE OF REVIEW: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of mature T-cell and natural killer (NK)-cell neoplasms in the WHO 2016 classification. Patient prognosis is poor when treated with CHOP, and there is an unmet need for new drugs. Several agents have been developed for PTCL, and their use is the subject of this review. RECENT FINDINGS: Phase 2 studies demonstrated the activity of new drugs in Relapsed/refractory PTCL. Only four compounds were approved by the food and drug administration: romidepsin and belinostat, which are epigenetic modifiers, the antifolate agent pralatrexate, the immuno-conjugate brentuximab vedotin...
September 2018: Current Opinion in Oncology
W V Lin, M Saumur, Z Al-Mohtaseb
Systemic autoimmune diseases are associated with ocular inflammatory conditions such as episcleritis, scleritis, keratitis, and uveitis. However, ocular manifestations have been reported to correlate with the extent of systemic disease. We present a patient with scleritis, keratitis, and orbital cellulitis, as the isolated manifestation of systemic lupus erythematosus (SLE). No microbial etiology was identified and antibiotics did not produce clinical improvement. The patient improved significantly with steroids and disease-modifying antirheumatic drugs...
August 9, 2018: Lupus
Mie Torii, Motomu Hashimoto, Akiko Hanai, Takao Fujii, Moritoshi Furu, Hiromu Ito, Ryuji Uozumi, Masahide Hamaguchi, Chikashi Terao, Wataru Yamamoto, Miyabi Uda, Kazuko Nin, Satoshi Morita, Hidenori Arai, Tsuneyo Mimori
OBJECTIVES: Sarcopenia is characterized by loss of muscle strength and mass, leading to falls and adverse health outcomes. Our aim was to determine the prevalence of sarcopenia in patients with rheumatoid arthritis (RA) and to identify factors associated with sarcopenia in these patients. METHODS: A cross-sectional study of 388 consecutive women with RA was conducted, assessing muscle mass and strength, and walking speed. Falls and bone fractures sustained over the prior year were evaluated...
August 9, 2018: Modern Rheumatology
Elsa Vieira-Sousa, Helena Canhão, Pedro Alves, Ana Maria Rodrigues, Filipa Teixeira, José Tavares-Costa, Alexandra Bernardo, Sofia Pimenta, Fernando Pimentel-Santos, João L Gomes, Renata Aguiar, Taciana Videira, Patrícia Pinto, Cristina Catita, Helena Santos, Joana Borges, Graça Sequeira, Célia Ribeiro, Lídia Teixeira, Pedro Ávila-Ribeiro, Fernando M Martins, Ruy M Ribeiro, João Eurico Fonseca
The GO-DACT is an investigator-initiated, national, multicentric randomized placebo-controlled double-blinded trial, that assesses dactylitis as primary endpoint. Psoriatic arthritis patients naïve to methotrexate and biologic disease modifying anti-rheumatic drugs, with at least one active dactylitis, were assigned to golimumab in combination with methotrexate or placebo in combination with methotrexate, for 24 weeks. Both clinical (dactylitis severity score and the Leeds dactylitis index) and imaging (high resolution magnetic resonance imaging), among others, were assessed as outcomes...
April 2018: Acta Reumatológica Portuguesa
James E Klaunig, Xilin Li, Zemin Wang
Non-alcoholic fatty liver disease is a major cause of chronic liver pathology in humans. Fatty liver disease involves the accumulation of hepatocellular fat in hepatocytes that can progress to hepatitis. Steatohepatitis is categorized into alcoholic (ASH) or non-alcoholic (NASH) steatohepatitis based on the etiology of the insult. Both pathologies involve an initial steatosis followed by a progressive inflammation of the liver and eventual hepatic fibrosis (steatohepatitis) and cirrhosis. The involvement of pharmaceuticals and other chemicals in the initiation and progression of fatty liver disease has received increased study...
July 1, 2018: Toxicology Research
Alessandra Almeida Filardy, Kamila Guimarães-Pinto, Marise Pinheiro Nunes, Ketiuce Zukeram, Lara Fliess, Ludimila Pereira, Danielle Oliveira Nascimento, Luciana Conde, Alexandre Morrot
Kinetoplastida trypanosomatidae microorganisms are protozoan parasites exhibiting a developmental stage in the gut of insect vectors and tissues of vertebrate hosts. During the vertebrate infective stages, these parasites alter the differential expression of virulence genes, modifying their biological and antigenic properties in order to subvert the host protective immune responses and establish a persistent infection. One of the hallmarks of kinetoplastid parasites is their evasion mechanisms from host immunity, leading to disease chronification...
2018: Frontiers in Immunology
Ageliki Laina, Aikaterini Gatsiou, Georgios Georgiopoulos, Kimon Stamatelopoulos, Konstantinos Stellos
Since our knowledge on structure and function of messenger RNA (mRNA) has expanded from merely being an intermediate molecule between DNA and proteins to the notion that RNA is a dynamic gene regulator that can be modified and edited, RNA has become a focus of interest into developing novel therapeutic schemes. Therapeutic modulation of RNA molecules by DNA- and RNA-based therapies has broadened the scope of therapeutic targets in infectious diseases, cancer, neurodegenerative diseases and most recently in cardiovascular diseases as well...
2018: Frontiers in Physiology
Paola Cassis, Monica Locatelli, Domenico Cerullo, Daniela Corna, Simona Buelli, Cristina Zanchi, Sebastian Villa, Marina Morigi, Giuseppe Remuzzi, Ariela Benigni, Carlamaria Zoja
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have pleiotropic properties beyond blood glucose-lowering effects and modify important nonglycemic pathways, leading to end-organ protection. SGLT2 inhibitors display renoprotective effects in diabetic kidney disease, which creates a rationale for testing the therapeutic potential of this drug class in nondiabetic chronic kidney disease. Here, we have shown that dapagliflozin provided glomerular protection in mice with protein-overload proteinuria induced by bovine serum albumin (BSA), to a similar extent as an ACE inhibitor used as standard therapy for comparison...
August 9, 2018: JCI Insight
Kani Zilbeyaz, Nashia Stellenboom, Murat Guney, Aykut Oztekin, Murat Senturk
There is a dire need for new treatments for Alzheimer's disease (AD). Principal drugs have reached maturity, and the number of people affected by AD is growing at a rapid rate. After years of research and many clinical trials, only symptomatic treatments are available. An effective disease-modifying drug for AD needs to be discovered. The research presented in this paper aims to facilitate in the discovery of new potential targets that could help in the ongoing AD research. Aryl methanesulfonate derivatives were screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities...
August 8, 2018: Journal of Biochemical and Molecular Toxicology
Sushruta S Hakkimane, Vishnu Prasad Shenoy, Santosh L Gaonkar, Indira Bairy, Bharath Raja Guru
Introduction: Tuberculosis (TB) is the single largest infectious disease which requires a prolonged treatment regime with multiple drugs. The present treatment for TB includes frequent administration of a combination of four drugs for a duration of 6 months. This leads to patient's noncompliance, in addition to developing drug-resistant strains which makes treatment more difficult. The formulation of drugs with biodegradable polymeric nanoparticles (NPs) promises to overcome this problem...
2018: International Journal of Nanomedicine
David Lichtstein, Asher Ilani, Haim Rosen, Noa Horesh, Shiv Vardan Singh, Nahum Buzaglo, Anastasia Hodes
Bipolar disorder (BD) is a severe and common chronic mental illness characterized by recurrent mood swings between depression and mania. The biological basis of the disease is poorly understood and its treatment is unsatisfactory. Although in past decades the "monoamine hypothesis" has dominated our understanding of both the pathophysiology of depressive disorders and the action of pharmacological treatments, recent studies focus on the involvement of additional neurotransmitters/neuromodulators systems and cellular processes in BD...
August 7, 2018: International Journal of Molecular Sciences
Ryan Paxman, Lars Plate, Erik A Blackwood, Chris Glembotski, Evan T Powers, R Luke Wiseman, Jeffery W Kelly
Pharmacologic arm-selective unfolded protein response (UPR) signaling pathway activation is emerging as a promising strategy to ameliorate imbalances in endoplasmic reticulum (ER) proteostasis implicated in diverse diseases. The small molecule N- (2-hydroxy-5-methylphenyl)-3-phenylpropanamide ( 147 ) was previously identified (<xref ref-type="bibr" rid="bib35">Plate et al., 2016</xref>) to preferentially activate the ATF6 arm of the UPR, promoting protective remodeling of the ER proteostasis network...
August 7, 2018: ELife
Cristiana Mollinari, Jian Zhao, Leonardo Lupacchini, Enrico Garaci, Daniela Merlo, Gang Pei
Neurodegenerative diseases are characterized by a gradual loss of cognitive and physical functions. Medications for these disorders are limited and treat the symptoms only. There are no disease-modifying therapies available, which have been shown to slow or stop the continuing loss of neurons. Transdifferentiation, whereby somatic cells are reprogrammed into another lineage without going through an intermediate proliferative pluripotent stem cell stage, provides an alternative strategy for regenerative medicine and disease modeling...
August 6, 2018: Cell Death & Disease
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