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https://www.readbyqxmd.com/read/27913990/sirukumab-a-potential-treatment-for-mood-disorders
#1
REVIEW
Aileen J Zhou, Yena Lee, Giacomo Salvadore, Benjamin Hsu, Trehani M Fonseka, Sidney H Kennedy, Roger S McIntyre
Convergent evidence indicates that abnormalities in the innate immune system may be pertinent to the pathogenesis, phenomenology, and possible treatment of several mental disorders. In keeping with this view, the targeting of interleukin-6 with the human monoclonal antibody sirukumab may represent a possible treatment and disease modification approach, for adults with brain-based disorders (e.g., major depressive disorder). A PubMed/Medline database search was performed using the following search terms: sirukumab; anti-IL-6; IL-6; major depressive disorder; inflammation...
December 2, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27911291/a-metal-free-method-for-producing-mri-contrast-at-amyloid-%C3%AE
#2
Silvia Hilt, Tang Tang, Jeffrey H Walton, Madhu Budamagunta, Izumi Maezawa, Tamás Kálai, Kálmán Hideg, Vikrant Singh, Heike Wulff, Qizhi Gong, Lee-Way Jin, Angelique Louie, John C Voss
Alzheimer's disease (AD) is characterized by depositions of the amyloid-β (Aβ) peptide in the brain. The disease process develops over decades, with substantial neurological loss occurring before a clinical diagnosis of dementia can be rendered. It is therefore imperative to develop methods that permit early detection and monitoring of disease progression. In addition, the multifactorial pathogenesis of AD has identified several potential avenues for AD intervention. Thus, evaluation of therapeutic candidates over lengthy trial periods also demands a practical, noninvasive method for measuring Aβ in the brain...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27910150/randomised-clinical-trial-exploratory-phase-2-study-of-ono-2952-in-diarrhoea-predominant-irritable-bowel-syndrome
#3
W E Whitehead, K Duffy, J Sharpe, T Nabata, M Bruce
BACKGROUND: ONO-2952 is a novel and selective inhibitor of translocator protein 18 kDa that reduces stress-induced defecation and visceral hyperalgesia in rat models. AIM: To evaluate the efficacy and safety of ONO-2952 in females with irritable bowel syndrome with diarrhoea in an exploratory proof-of-concept study. METHODS: A randomised, double-blind, placebo-controlled study was conducted at 49 US centres. Two hundred subjects with irritable bowel syndrome with diarrhoea (Rome III criteria) were randomised to ONO-2952 20 mg, or 60 mg, or placebo...
January 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27908828/assessment-of-the-potential-for-host-targeted-iminosugars-uv-4-and-uv-5-activity-against-filovirus-infections-in-vitro-and-in-vivo
#4
Kelly L Warfield, Travis K Warren, Xiangguo Qiu, Jay Wells, Chad E Mire, Joan B Geisbert, Kelly S Stuthman, Nicole L Garza, Sean A Van Tongeren, Amy C Shurtleff, Krystle N Agans, Gary Wong, Michael V Callahan, Thomas W Geisbert, Brennan Klose, Urban Ramstedt, Anthony M Treston
Iminosugars are host-directed antivirals with broad-spectrum activity. The iminosugar, N-butyl-deoxynojirimycin (NB-DNJ or Miglustat(®)), is used in humans for treatment of Gaucher's disease and has mild antiviral properties. More potent analogs of NB-DNJ have been generated and have demonstrated activity against a variety of viruses including flaviviruses, influenza, herpesviruses and filoviruses. In the current study, a panel of analogs based on NB-DNJ was analyzed for activity against Ebola (EBOV) and Marburg viruses (MARV)...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27898045/dendritic-cell-based-immunotherapies-to-fight-hiv-how-far-from-a-success-story-a-systematic-review-and-meta-analysis
#5
REVIEW
Antonio Victor Campos Coelho, Ronald Rodrigues de Moura, Anselmo Jiro Kamada, Ronaldo Celerino da Silva, Rafael Lima Guimarães, Lucas André Cavalcanti Brandão, Luiz Cláudio Arraes de Alencar, Sergio Crovella
The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports...
November 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27897416/curcumin-an-effective-adjunct-in-patients-with-statin-associated-muscle-symptoms
#6
REVIEW
Amirhossein Sahebkar, Nikou Saboni, Matteo Pirro, Maciej Banach
In spite of the unequivocal efficacy of statins in reducing primary and secondary cardiovascular events, the use of these drugs in a considerable number of patients is limited because of statin intolerance, mainly statin-associated muscle symptoms (SAMS). SAMS encompass a broad spectrum of clinical presentations, including mild muscular aching and other types of myalgias, myopathy with the significant elevation of creatine kinase, and the rare but life-threatening rhabdomyolysis. Among several pathophysiologic mechanisms of SAMS, mitochondrial dysfunction is thought to be one of the main one...
September 22, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27892422/prognostic-value-of-serial-six-minute-walk-tests-using-tele-accelerometry-in-patients-with-chronic-heart-failure-a-pre-specified-sub-study-of-the-tim-hf-trial
#7
Sandra Prescher, Christoph Schoebel, Kerstin Koehler, Oliver Deckwart, Brunhilde Wellge, Marcus Honold, Oliver Hartmann, Sebastian Winkler, Friedrich Koehler
BACKGROUND: The six-minute walk test (6MWT) is an established functional test assessing exercise capacity and is used to predict clinical prognosis in patients with chronic heart failure (HF). Tele-accelerometry is a novel approach to activity monitoring using telemedical data transfer and allows a Tele-6MWT to be performed in an outpatient setting. It offers patients the option of performing simple serial follow-up tests in their own home. AIMS: The aim of this study was to investigate the prognostic value of serial Tele-6MWTs using tele-accelerometry in patients with HF...
October 2016: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/27889256/controlled-human-infection-with-rsv-the-opportunities-of-experimental-challenge
#8
Maximillian S Habibi, Christopher Chiu
Despite the recent explosion in RSV vaccine development, there remain substantial hurdles to overcome before licensing of effective vaccines will allow widespread use, particularly in high-risk populations. Incomplete understanding of mechanisms and correlates of protection against RSV mean that, for the time being, successful RSV vaccines must directly demonstrate efficacy, which necessitates large and costly clinical trials in naturally infected patients. To mitigate the risks inherent in progressing to these late-stage trials, experimental human RSV infection studies have recently been re-established, representing the interface between pre-clinical models and observational studies of patients...
November 23, 2016: Vaccine
https://www.readbyqxmd.com/read/27885887/cell-therapies-for-parkinson-s-disease-how-far-have-we-come
#9
Thomas B Stoker, Roger A Barker
Over the past three decades, significant progress has been made in the development of potential regenerative cell-based therapies for neurodegenerative disease, with most success being seen in Parkinson's disease. Cell-based therapies face many challenges including ethical considerations, potential for immune-mediated rejection with allogeneic and xenogeneic tissue, pathological spread of protein-related disease into the grafted tissue as well as the risk of graft overgrowth and tumorigenesis in stem cell-derived transplants...
December 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27884198/use-of-poly-adp-ribose-polymerase-parp-inhibitors-in-cancer-cells-bearing-ddr-defects-the-rationale-for-their-inclusion-in-the-clinic
#10
REVIEW
Aniello Cerrato, Francesco Morra, Angela Celetti
BACKGROUND: DNA damage response (DDR) defects imply genomic instability and favor tumor progression but make the cells vulnerable to the pharmacological inhibition of the DNA repairing enzymes. Targeting cellular proteins like PARPs, which cooperate and complement molecular defects of the DDR process, induces a specific lethality in DDR defective cancer cells and represents an anti-cancer strategy. Normal cells can tolerate the DNA damage generated by PARP inhibition because of an efficient homologous recombination mechanism (HR); in contrast, cancer cells with a deficient HR are unable to manage the DSBs and appear especially sensitive to the PARP inhibitors (PARPi) effects...
November 24, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27883925/factors-associated-with-failure-of-oncology-drugs-in-late-stage-clinical-development-a-systematic-review
#11
REVIEW
Denis L Jardim, Eric S Groves, Philip P Breitfeld, Razelle Kurzrock
BACKGROUND: We aimed to describe the reasons for failure of experimental anticancer drugs in late-stage clinical development. MATERIAL AND METHODS: We searched the PharmaProjects database (https://citeline.com/products/pharmaprojects/) for anticancer drugs discontinued between 01/01/2009 and 06/30/2014. Drug programs that reached phase III trials, but never gained Food and Drug Administration (FDA) approval were compared to 37 anti-cancer drugs achieving FDA approval in this time period...
November 4, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27879370/validation-of-mri-determination-on-pet-measurements-in-ischemic-stroke
#12
Wolf-Dieter Heiss, Olivier Zaro Weber
The concept of the ischemic penumbra was formulated based on animal experiments showing functional impairment and electrophysiological disturbances with decreasing flow to the brain below defined values (the threshold for function) and irreversible tissue damage with blood supply further decreased (the threshold for infarction). The perfusion range between these thresholds was termed "penumbra", and restitution of flow above the functional threshold was able to reverse the deficits without permanent damage...
November 22, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27876460/imo-8400-a-toll-like-receptor-7-8-and-9-antagonist-demonstrates-clinical-activity-in-a-phase-2a-randomized-placebo-controlled-trial-in-patients-with-moderate-to-severe-plaque-psoriasis
#13
Deepak M W Balak, Martijn B A van Doorn, Robert D Arbeit, Rianne Rijneveld, Erica Klaassen, Tim Sullivan, Julie Brevard, H Bing Thio, Errol P Prens, J Koos Burggraaf, Robert Rissmann
BACKGROUND: Aberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self-nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs 7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy of IMO-8400 in a first-in-patient phase 2 trial. METHODS: Forty-six psoriasis patients were randomly assigned to IMO-8400 in four dose levels or placebo for 12weeks...
November 19, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27874011/inhibition-of-glycine-transporter-1-in-the-dorsal-vagal-complex-improves-metabolic-homeostasis-in-diabetes-and-obesity
#14
Jessica T Y Yue, Mona A Abraham, Paige V Bauer, Mary P LaPierre, Peili Wang, Frank A Duca, Beatrice M Filippi, Owen Chan, Tony K T Lam
Impaired glucose homeostasis and energy balance are integral to the pathophysiology of diabetes and obesity. Here we show that administration of a glycine transporter 1 (GlyT1) inhibitor, or molecular GlyT1 knockdown, in the dorsal vagal complex (DVC) suppresses glucose production, increases glucose tolerance and reduces food intake and body weight gain in healthy, obese and diabetic rats. These findings provide proof of concept that GlyT1 inhibition in the brain improves glucose and energy homeostasis. Considering the clinical safety and efficacy of GlyT1 inhibitors in raising glycine levels in clinical trials for schizophrenia, we propose that GlyT1 inhibitors have the potential to be repurposed as a treatment of both obesity and diabetes...
November 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27868341/a-single-arm-trial-indirect-comparison-investigation-a-proof-of-concept-method-to-predict-venous-leg-ulcer-healing-time-for-a-new-acellular-synthetic-matrix-matched-to-standard-care-control
#15
Ronald Shannon, Andrea Nelson
To compare data on time to healing from two separate cohorts: one treated with a new acellular synthetic matrix plus standard care (SC) and one matched from four large UK pragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence network]. We introduce a new proof-of-concept strategy to a VLU clinical evidence network, propensity score matching and sensitivity analysis to predict the feasibility of the new acellular synthetic matrix plus SC for success in future randomised, controlled clinical trials...
November 20, 2016: International Wound Journal
https://www.readbyqxmd.com/read/27865174/maraviroc-in-addition-to-cart-during-primary-hiv-infection-results-from-main-randomized-clinical-trial-and-96-weeks-follow-up
#16
Marco Ripa, Manuela Pogliaghi, Stefania Chiappetta, Silvia Nozza, Alessandro Soria, Giacomo Coppalini, Cristina Rovelli, Giuseppe Tambussi
BACKGROUND: Multi-targeted treatment strategies including maraviroc (MVC) during Primary HIV Infection (PHI) may benefit from the immune-modulatory properties of this CCR5-inhibitor. OBJECTIVES: We conducted a proof-of-concept clinical trial aimed at assessing whether maraviroc in addition of a combination antiretroviral therapy (cART) initiated during PHI would improve immunological and virological parameters. STUDY DESIGN: The MAIN (Maraviroc in HIV Acute INfection) study was a randomized open-label clinical trial (EUDRACT number: 2008-007004-29) which enrolled 29 patients with PHI...
October 31, 2016: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/27862847/development-of-australia-s-first-older-adult-specific-early-intervention-for-alcohol-related-harm-feasibility-and-proof-of-concept
#17
Stephen J Bright, Cylie M Williams
OBJECTIVES: The rate of older Australians at risk of experiencing alcohol-related harm increased by 31% over the past 10 years, yet there are no Australian age-specific early interventions. We describe the development of Australia's first age-specific early intervention protocol. METHODS: Through examining effective overseas older adult-specific interventions, in addition to other relevant literature, an early intervention protocol was developed. RESULTS: The Older Wiser Lifestyles (OWL) early intervention protocol extends protocols that have been developed overseas through providing: (i) interventions that are tailored to the person's readiness to change, including the provision of harm reduction strategies for people who are precontemplative; and (ii) individualised psychoeducational materials regarding medical conditions and medications...
November 14, 2016: Australasian Journal on Ageing
https://www.readbyqxmd.com/read/27861905/attenuation-of-experimental-autoimmune-neuritis-with-locally-administered-lovastatin-encapsulating-plga-nanoparticles
#18
Kelly A Langert, Bruktawit Goshu, Evan B Stubbs
Acute inflammatory demyelinating polyneuropathy (AIDP) is an aggressive antibody- and T cell-mediated variant of Guillain-Barré Syndrome (GBS), a prominent and debilitating autoimmune disorder of the peripheral nervous system. Despite advancements in clinical management, treatment of patients with AIDP/GBS and its chronic variant CIDP remains palliative and relies on the use of non-specific immune-modulating therapies. Our laboratory has previously reported that therapeutic administration of statins safely attenuates the clinical severity of experimental autoimmune neuritis (EAN), a well-characterized animal model of AIDP/GBS, by restricting the migration of autoreactive leukocytes across peripheral nerve microvascular endoneurial endothelial cells (PNMECs) that form the blood-nerve barrier...
November 8, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27852560/safety-acceptability-and-use-of-a-smartphone-app-blueice-for-young-people-who-self-harm-protocol-for-an-open-phase-i-trial
#19
Paul Stallard, Joanna Porter, Rebecca Grist
BACKGROUND: Up to 18% of adolescents will engage in an act of self-harm before young adulthood, with the majority of acts occurring in private. Mobile apps may offer a way of providing support for young people at times of distress to prevent self-harm. OBJECTIVE: This is a proof-of-concept study designed to explore the safety, acceptability, feasibility, and usability of a smartphone app, BlueIce, with young people who are self-harming. METHODS: In this phase I open trial we will evaluate BlueIce, a smartphone app developed and coproduced with young people with lived experience of self-harm...
November 16, 2016: JMIR Research Protocols
https://www.readbyqxmd.com/read/27846049/agomelatine-for-the-treatment-of-major-depressive-episodes-in-schizophrenia-spectrum-disorders-an-open-prospective-proof-of-concept-study
#20
Susanne Englisch, Hanna Sophie Jung, Antje Lewien, Anna Becker, Ulrike Nowak, Hanna Braun, Jascha Thiem, Sarah Eisenacher, Andreas Meyer-Lindenberg, Mathias Zink
BACKGROUND: Depressive episodes in schizophrenia constitute a major clinical problem, and treatment success is often limited by treatment-emergent side effects. Agomelatine, an agonist at melatonergic MT1/MT2 receptors and 5-HT2C receptor antagonist, is a new antidepressant with a novel mode of action which constitutes a potential therapeutic option for depression in schizophrenia. METHODS: Twenty-seven patients with lifetime diagnoses within the schizophrenia spectrum and comorbid depression were treated with agomelatine in addition to stable doses of antipsychotic agents...
October 29, 2016: Journal of Clinical Psychopharmacology
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