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https://www.readbyqxmd.com/read/29684591/in-vitro-and-in-vivo-activity-of-opioid-cyclopeptide-with-mu-delta-agonist-profile-biased-toward-%C3%AE-arrestin
#1
Katarzyna Gach-Janczak, Justyna Piekielna-Ciesielska, Anna Adamska-Bartłomiejczyk, Karol Wtorek, Federica Ferrari, Girolamo Calo, Agata Szymaszkiewicz, Joanna Piasecka-Zelga, Anna Janecka
Replacement of the tyrosine residue in the mu-selective opioid ligand Tyr-c[D-Lys-Phe-Asp]NH2 with 2',6'-dimethyltyrosine (Dmt) produced a cyclopeptide Dmt-c[D-Lys-Phe-Asp]NH2 with mu/delta opioid receptor agonist profile. This new analog showed improved antinociception in the hot-plate test as compared to the parent but also significantly inhibited the gastrointestinal transit. Using the bioluminescence resonance energy transfer (BRET) assay it was shown that this analog was biased toward β-arrestin.
April 20, 2018: Peptides
https://www.readbyqxmd.com/read/29684426/mitochondria-targeting-nanomedicine-an-effective-and-potent-strategy-against-aminoglycosides-induced-ototoxicity
#2
Shuang Zhou, Yanhui Sun, Xiao Kuang, Shanshan Hou, YinXian Yang, Zhenjie Wang, Hongzhuo Liu
We report a proof-of-concept for the development of mitochondria-targeting nanoparticles (NPs) loaded with geranylgeranylacetone (GGA) to protect against a wide range of gentamicin-induced ototoxicity symptoms in a zebrafish model. The polymeric NPs were functionalized with a mitochondrial-homing peptide (d‑Arg‑Dmt‑Orn‑Phe‑NH2 ) and exhibited greater mitochondrial uptake and lower gentamicin uptake in hair cells via mechanotransduction (MET) channels and tuned machinery in the hair bundle than the ordinary NPs did...
April 20, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29682363/acute-intoxication-following-dimethyltryptamine-ingestion
#3
Matthew H Bilhimer, Rachel F Schult, Kristan V Higgs, Timothy J Wiegand, Rachel M Gorodetsky, Nicole M Acquisto
Ayahuasca is a hallucinogenic tea that is most commonly comprised of the vine Banisteriopsis caapi alone or in combination with other plants such as Psychotria viridis . This concoction results in an orally active form of dimethyltryptamine (DMT), a hallucinogenic amine. Despite use in South America as a medicinal agent and component in religious ceremonies, interest in its recreational use and spiritual effects has led to increased use in the United States. We describe a unique case following ingestion of ayahuasca tea in a patient with history of schizophrenia resulting in personal injury and property damage...
2018: Case Reports in Emergency Medicine
https://www.readbyqxmd.com/read/29674970/hypothesis-the-psychedelic-ayahuasca-heals-traumatic-memories-via-a-sigma-1-receptor-mediated-epigenetic-mnemonic-process
#4
Antonio Inserra
Ayahuasca ingestion modulates brain activity, neurotransmission, gene expression and epigenetic regulation. N,N -Dimethyltryptamine (DMT, one of the alkaloids in Ayahuasca) activates sigma 1 receptor (SIGMAR1) and others. SIGMAR1 is a multi-faceted stress-responsive receptor which promotes cell survival, neuroprotection, neuroplasticity, and neuroimmunomodulation. Simultaneously, monoamine oxidase inhibitors (MAOIs) also present in Ayahuasca prevent the degradation of DMT. One peculiarity of SIGMAR1 activation and MAOI activity is the reversal of mnemonic deficits in pre-clinical models...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29666929/development-of-physical-fitness-in-austrian-primary-school-children-a-longitudinal-study-among-overweight-and-non-overweight-children-over-2-5-years
#5
Gerhard Ruedl, Dominik Franz, Anika Frühauf, Martin Kopp, Martin Niedermeier, Clemens Drenowatz, Klaus Greier
BACKGROUND: Physical activity and physical fitness play an important role in the prevention of overweight and obesity in childhood and adolescence and reduce the risk of becoming overweight or obese in adulthood. AIM: To evaluate the development of physical fitness in overweight and non-overweight primary school children from the first to third grades. METHODS: Using a longitudinal study design, body height and weight as well as physical fitness of primary school children from Tyrol, Austria were measured five times during a period of 2...
April 17, 2018: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/29664276/effects-of-n-n-dimethyltryptamine-dmt-on-rat-behaviors-relevant-to-anxiety-and-depression
#6
Lindsay P Cameron, Charlie J Benson, Lee E Dunlap, David E Olson
Depression and anxiety disorders are debilitating diseases resulting in substantial economic costs to society. Traditional antidepressants often take weeks to months to positively affect mood and are ineffective for about 30% of the population. Alternatives, such as ketamine, a dissociative anesthetic capable of producing hallucinations, and the psychoactive tisane ayahuasca have shown great promise due to their fast-acting nature and effectiveness in treatment-resistant populations. Here, we investigate the effects of N,N-dimethyltryptamine (DMT), the principle hallucinogenic component of ayahuasca, in rodent behavioral assays relevant to anxiety and depression using adult, male, Sprague-Dawley rats...
April 17, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29660915/hemorheological-and-metabolic-consequences-of-renal-ischemia-reperfusion-and-their-modulation-by-n-n-dimethyl-tryptamine-on-a-rat-model
#7
Katalin Peto, Norbert Nemeth, Anita Mester, Zsuzsanna Magyar, Souleiman Ghanem, Viktoria Somogyi, Bence Tanczos, Adam Deak, Laszlo Bidiga, Ede Frecska, Balazs Nemes
BACKGROUND: Micro-rheological relations of renal ischemia-reperfusion (I/R) have not been completely elucidated yet. Concerning anti-inflammatory agents, it is supposed that sigma-1 receptor agonist N,N-dimethyl-tryptamin (DMT) can be useful to reduce I/R injury. OBJECTIVE: To investigate the micro-rheological and metabolic parameters, and the effects of DMT in renal I/R in rats. METHODS: In anesthetized rats from median laparotomy both kidneys were exposed...
April 13, 2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29629942/paediatric-multiple-sclerosis-and-other-acute-demyelinating-diseases
#8
Kevin Rostásy, Barbara Bajer-Kornek
PURPOSE OF REVIEW: Neuroimmunological diseases encompass a wide spectrum of diseases in children. Apart from the discovery of autoantibodies affecting primarily grey matter structures and the improved clinical characterization of rare entities such as N-methyl D-aspartate receptor-R- encephalitis, important strides have also been made in autoimmune-mediated white matter diseases, including paediatric multiple sclerosis (pedMS) and other acute demyelinating syndromes (ADS) often associated with antibodies (abs) against myelin-oligodendrocyte-glycoprotein (MOG)...
April 7, 2018: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29627873/disease-modifying-treatment-in-progressive-multiple-sclerosis
#9
REVIEW
John Robert Ciotti, Anne Haney Cross
PURPOSE OF REVIEW: Multiple sclerosis (MS) is an immune-mediated disorder that affects the central nervous system (CNS), often first affecting people in early adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at disease onset, a substantial proportion later develop chronic progression, termed secondary progressive MS (SPMS). Approximately 10% of MS patients experience chronic progression from disease onset, termed primary progressive multiple sclerosis (PPMS)...
April 7, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29618273/cost-effectiveness-of-cladribine-tablets-alemtuzumab-and-natalizumab-in-the-treatment-of-relapsing-remitting-multiple-sclerosis-with-high-disease-activity-in-england
#10
Robert Hettle, Gerard Harty, Schiffon L Wong
AIMS: Cladribine tablets is the first oral short-course treatment approved for highly active relapsing multiple sclerosis (MS). The Association of British Neurologists guidelines currently recommend two infusion therapies, alemtuzumab and natalizumab, to treat high disease activity relapsing remitting MS (HDA-RRMS). This analysis assessed the cost-effectiveness of cladribine tablets in HDA-RRMS compared with alemtuzumab and natalizumab, from the perspective of the National Health Service (NHS) in England...
April 5, 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/29615905/four-weekly-ayahuasca-sessions-lead-to-increases-in-acceptance-capacities-a-comparison-study-with-a-standard-8-week-mindfulness-training-program
#11
Joaquim Soler, Matilde Elices, Elisabeth Dominguez-Clavé, Juan C Pascual, Amanda Feilding, Mayte Navarro-Gil, Javier García-Campayo, Jordi Riba
Background: The therapeutic effects of the Amazonian plant tea ayahuasca may relate to its ability to enhance mindfulness capacities. Ayahuasca induces a modified state of awareness through the combined action of its active principles: the psychedelic N,N- dimethyltryptamine (DMT) and a series of centrally acting β-carbolines, mainly harmine and tetrahydroharmine. To better understand the therapeutic potential of ayahuasca, here we compared the impact on mindfulness capacities induced by two independent interventions: (a) participation in four ayahuasca sessions without any specific purpose related to improving mindfulness capacities; and (b) participation in a standard mindfulness training course: 8 weeks mindfulness-based stress reduction (MBSR), with the specific goal of improving these skills...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29609364/digital-to-analog-converters-for-high-speed-optical-communications-using-frequency-interleaving-impairments-and-characteristics
#12
Christian Schmidt, Christoph Kottke, Ronald Freund, Friedel Gerfers, Volker Jungnickel
Digital-to-analog converters (DACs) for high-speed optical communication systems based on CMOS technology have bandwidths lower than nowadays electro-optic components. A promising concept to circumvent this bottleneck is the frequency-interleaved DAC (FI-DAC) concept. In this paper, experimental results for the application of a 180 GS/s FI-DAC with 40 GHz analog bandwidth based on two DACs in a high-speed optical link are discussed and compared with simulation results. Thereby, phase and power mismatches, spectral overlap, clipping and the required DAC resolution are investigated...
March 19, 2018: Optics Express
https://www.readbyqxmd.com/read/29602795/disease-modifying-drugs-for-multiple-sclerosis-and-infection-risk-a-cohort-study
#13
José Maria Andreas Wijnands, Feng Zhu, Elaine Kingwell, John David Fisk, Charity Evans, Ruth Ann Marrie, Yinshan Zhao, Helen Tremlett
OBJECTIVE: Little is known about disease-modifying treatments (DMTs) for multiple sclerosis (MS) and infection risk in clinical practice. We examined the association between DMTs and infection-related medical encounters. METHODS: Using population-based administrative data from British Columbia, Canada, we identified MS cases and followed them from their first demyelinating event (1996-2013) until emigration, death or study end (December 2013). Associations between DMT exposure (by DMT generation or class) and infection-related physician or hospital claims were assessed using recurrent time-to-events models, adjusted for age, sex, socioeconomic status, index year and comorbidity count...
March 30, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29595337/mitochondria-homing-peptide-functionalized-nanoparticles-performing-dual-extracellular-intracellular-roles-to-inhibit-aminoglycosides-induced-ototoxicity
#14
Shuang Zhou, Yanhui Sun, Xiao Kuang, Shanshan Hou, Zhenjie Wang, Zhe Qian, Hongzhuo Liu
One of the major challenges in the treatment of hearing loss is the low efficacy of therapeutic candidates. To achieve the optimum drug efficacy, we designed a novel peptide (D-Arg-Dmt-Arg-Phe-NH2 )-mediated mitochondrial targeted delivery nanosystem for a promising candidate, geranylgeranylacetone (GGA). The zebrafish lateral line system, a robust model for mammalian hair cells, was used to identify the efficacy against gentamicin, a well-known ototoxic agent. The nanosystem facilitated lysosomal escape and mitochondrial accumulation, and thus conferred superior protective efficacy against a wide range of gentamicin compared with unmodified NPs and free drugs...
March 29, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29583054/sequencing-of-disease-modifying-therapies-for-relapsing-remitting-multiple-sclerosis-a-theoretical-approach-to-optimizing-treatment
#15
Francois Grand'Maison, Michael Yeung, Sarah A Morrow, Liesly Lee, Francois Emond, Brian J Ward, Pierre Laneuville, Robyn Schecter
Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing-remitting MS (RRMS), which is the most prevalent phenotype. The chronic nature of the disease and the multiple treatment options make benefit-risk-based sequencing of therapy essential to ensure optimal care...
March 27, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29578855/a-comparison-of-pharmacy-dispensing-channel-use-and-adherence-to-specialty-drugs-among-medicare-part-d-beneficiaries
#16
Hrishikesh P Kale, Anisha M Patel, Norman V Carroll
BACKGROUND: Nonadherence to specialty drugs has been associated with poor clinical and economic outcomes. Studies conducted using commercial health plans suggest that patients who use specialty pharmacies have higher adherence compared with patients using retail pharmacies. However, little is known about the frequency of dispensing channel use or the association of dispensing channel use with adherence to specialty drugs among Medicare Part D beneficiaries. OBJECTIVES: To (a) describe the use of pharmacy dispensing channels by patients using self-administered specialty drugs in Medicare Part D and (b) study the association between dispensing channel use and adherence to specialty drugs in this population...
April 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29562511/clinical-trials-for-disease-modifying-therapies-in-alzheimer-s-disease-a-primer-lessons-learned-and-a-blueprint-for-the-future
#17
Jeffrey Cummings, Aaron Ritter, Kate Zhong
Alzheimer's disease (AD) has no currently approved disease-modifying therapies (DMTs), and treatments to prevent, delay the onset, or slow the progression are urgently needed. A delay of 5 years if available by 2025 would decrease the total number of patients with AD by 50% in 2050. To meet the definition of DMT, an agent must produce an enduring change in the course of AD; clinical trials of DMTs have the goal of demonstrating this effect. AD drug discovery entails target identification followed by high throughput screening and lead optimization of drug-like compounds...
March 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29557704/discontinuation-of-disease-modifying-therapy-in-patients-with-multiple-sclerosis-over-age-60
#18
Le H Hua, Tracey H Fan, Devon Conway, Nicolas Thompson, Tyler G Kinzy
BACKGROUND: The risk-benefit ratio of continuing immunomodulating disease-modifying therapy (DMT) in older multiple sclerosis (MS) patients is unknown. OBJECTIVE: To evaluate clinical and patient-reported outcomes after stopping DMT in older MS patients. METHODS: Retrospective, observational study identifying patients from our MS clinics who were aged over 60 and on DMT > 2 years. Cause-specific Cox proportional hazards regression modeled time to discontinuation and time to reinitiation of therapy...
March 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29549468/a-multicentre-observational-analysis-of-persistence-to-treatment-in-the-new-multiple-sclerosis-era-the-respect-study
#19
Roberta Lanzillo, Luca Prosperini, Claudio Gasperini, Marcello Moccia, Roberta Fantozzi, Carla Tortorella, Viviana Nociti, Pietro Annovazzi, Paola Cavalla, Marta Radaelli, Simona Malucchi, Valentina Torri Clerici, Laura Boffa, Fabio Buttari, Paolo Ragonese, Giorgia Teresa Maniscalco, Massimiliano Di Filippo, Maria Chiara Buscarinu, Federica Pinardi, Antonio Gallo, Giancarlo Coghe, Ilaria Pesci, Alice Laroni, Alberto Gajofatto, Massimiliano Calabrese, Valentina Tomassini, Eleonora Cocco, Claudio Solaro
In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing-remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12 months...
March 16, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29543291/anti-hiv-activity-of-new-higher-order-g-quadruplex-aptamers-obtained-from-tetra-end-linked-oligonucleotides
#20
F Nici, G Oliviero, A P Falanga, S D'Errico, M Marzano, D Musumeci, D Montesarchio, S Noppen, C Pannecouque, G Piccialli, N Borbone
By combining the ability of short G-rich oligodeoxyribonucleotides (ODNs) containing the sequence 5'CGGA3' to form higher order G-quadruplex (G4) complexes with the tetra-end-linked (TEL) concept to produce aptamers targeting the HIV envelope glycoprotein 120 (gp120), three new TEL-ODNs (1-3) having the sequence 5'CGGAGG3' were synthesized with the aim of studying the effect of G4 dimerization on their anti-HIV activity. Furthermore, in order to investigate the effect of the groups at the 5' position, the 5' ends of 1-3 were left uncapped (1) or capped with either the lipophilic dimethoxytrityl (DMT) (2) or the hydrophilic glucosyl-4-phosphate (3) moieties...
March 15, 2018: Organic & Biomolecular Chemistry
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