Search results for "Therapeutics"
showing 10 items of 489 documents
Glaucoma and Antioxidants: Review and Update
2020
Glaucoma is a neurodegenerative disease characterised by the progressive degeneration of retinal ganglion cells. Oxidative stress has been related to the cell death in this disease. Theoretically, this deleterious consequence can be reduced by antioxidants substances. The aim of this review is to assemble the studies published in relation to antioxidant supplementation and its effects on glaucoma and to offer the reader an update on this field. With this purpose, we have included studies in animal models of glaucoma and clinical trials. Although there are variable results, supplementation with antioxidants in glaucoma may be a promising therapy in glaucoma.
Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy
2021
Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by expansion of unstable CTG repeats in a non-coding region of the DMPK gene. CUG expansions in mutant DMPK transcripts sequester MBNL1 proteins in ribonuclear foci. Depletion of this protein is a primary contributor to disease symptoms such as muscle weakness and atrophy and myotonia, yet upregulation of endogenous MBNL1 levels may compensate for this sequestration. Having previously demonstrated that antisense oligonucleotides against miR-218 boost MBNL1 expression and rescue phenotypes in disease models, here we provide preclinical characterization of an antagomiR-218 molecule using the HSALR mouse model and patient-d…
Musashi-2 contributes to myotonic dystrophy muscle dysfunction by promoting excessive autophagy through miR-7 biogenesis repression
2021
Skeletal muscle symptoms strongly contribute to mortality of myotonic dystrophy type 1 (DM1) patients. DM1 is a neuromuscular genetic disease caused by CTG repeat expansions that, upon transcription, sequester the Muscleblind-like family of proteins and dysregulate alternative splicing of hundreds of genes. However, mis-splicing does not satisfactorily explain muscle atrophy and wasting, and several other contributing factors have been suggested, including hyperactivated autophagy leading to excessive catabolism. MicroRNA ( miR ) -7 has been demonstrated to be necessary and sufficient to repress the autophagy pathway in cell models of the disease, but the origin of its low levels in DM1 was…
Quantity and Quality of Aquaculture Enrichments Influence Disease Epidemics and Provide Ecological Alternatives to Antibiotics
2021
Environmental heterogeneity is a central component influencing the virulence and epidemiology of infectious diseases. The number and distribution of susceptible hosts determines disease transmission opportunities, shifting the epidemiological threshold between the spread and fadeout of a disease. Similarly, the presence and diversity of other hosts, pathogens and environmental microbes, may inhibit or accelerate an epidemic. This has important applied implications in farming environments, where high numbers of susceptible hosts are maintained in conditions of minimal environmental heterogeneity. We investigated how the quantity and quality of aquaculture enrichments (few vs. many stones
Comparison of Shod and Unshod Gait in Patients With Parkinson's Disease With Subthalamic and Nigral Stimulation
2022
Background: The Parkinsonian [i.e., Parkinson's disease (PD)] gait disorder represents a therapeutical challenge with residual symptoms despite the use of deep brain stimulation of the subthalamic nucleus (STN DBS) and medical and rehabilitative strategies. The aim of this study was to assess the effect of different DBS modes as combined stimulation of the STN and substantia nigra (STN+SN DBS) and environmental rehabilitative factors as footwear on gait kinematics.Methods: This single-center, randomized, double-blind, crossover clinical trial assessed shod and unshod gait in patients with PD with medication in different DBS conditions (i.e., STIM OFF, STN DBS, and STN+SN DBS) during differe…
Polymer-drug conjugates as platforms for combination therapy in the treatment of hormone-dependent breast cancer
2013
1. Objetivos de la Investigación. Los conjugados poliméricos son nanoconstrucciones multicomponente presentes actualmente en clínica como terapia anticancerígena, tanto como agentes únicos, como formando parte de combinaciones. Estos nanoconjugados tienen el potencial de mejorar farmacológicamente el tratamiento de tumores sólidos, debido a una acumulación pasiva en el tumor (efecto ‘EPR’) y a un diferente mecanismo de internalización celular y posterior liberación del fármaco(s). La transferencia de conjugados polímero-proteína a uso clínico rutinario, y el desarrollo clínico de conjugados polímero-fármaco anticancerígeno sitúa a los conjugados poliméricos como una de las primeras clases d…
Is it the time of seno-therapeutics application in cardiovascular pathological conditions related to ageing?
2021
It rates that in 2030, the cardiovascular diseases (CVD) will result in 40% of all deaths and rank as the leading cause. Thus, the research of appropriate therapies able to delay or retard their onset and progression is growing. Of particular interest is a new branch of the medical science, called anti-ageing medicine since CVD are the result of cardiovascular ageing. Senescent cells (SC) accumulate in cardiovascular system contributing to the onset of typical age-related cardiovascular conditions (i.e., atherosclerosis, medial aorta degeneration, vascular remodeling, stiffness). Such conditions progress in cardiovascular pathologies (i.e., heart failure, coronary artery disease, myocardial…
Docetaxel-Loaded Nanoparticles Assembled from β-Cyclodextrin/Calixarene Giant Surfactants: Physicochemical Properties and Cytotoxic Effect in Prostat…
2017
Giant amphiphiles encompassing a hydrophilic β-cyclodextrin (βCD) component and a hydrophobic calix[4]arene (CA4) module undergo self-assembly in aqueous media to afford core-shell nanospheres or nanocapsules, depending on the nanoprecipitation protocol, with high docetaxel (DTX) loading capacity. The blank and loaded nanoparticles have been fully characterized by dynamic light scattering (DLS), ζ-potential measurements and cryo-transmission electron microscopy (cryo-TEM). The data are compatible with the distribution of the drug between the nanoparticle core and the shell, where it is probably anchored by inclusion of the DTX aromatic moieties in βCD cavities. Indeed, the release kinetics …
Mucoadhesive Polymer Hyaluronan as Biodegradable Cationic/Zwitterionic-Drug Delivery Vehicle
2014
Mucoadhesive polymers in pharmaceutical formulations release drugs in mucosal areas. They interact and fix to mucus via molecular interpenetration, etc ., which increase drug bioavailability. Polymers physicochemical properties affect formulation mucoadhesion, rheological behaviour and drug absorption. Hyaluronan (HA) is selected as a mucoadhesive and biodegradable polymer. Geometric, topological and fractal analyses are carried out with program TOPO. Reference calculations are performed with algorithm GEPOL. Procedure TOPO underestimates molecular volume by 0.7%. Error results 5% in surface area and derived topological indices. Solvent-accessible surface is undercalculated by 3%: from hexa…
Detoxication Strategy of Epoxide Hydrolase—The Basis for a Novel Threshold for Definable Genotoxic Carcinogens
2004
From our recent work on the three-dimensional structure of epoxide hydrolases we theoretically deduced the likelihood of a two-step catalytic mechanism that we and others have subsequently experimentally confirmed. Analysis of the rate of the two steps by us and by others show that the first step—responsible for removal of the reactive epoxide from the system—works extraordinarily fast (typically three orders of magnitude faster than the second step), sucking up the epoxide like a sponge. Regeneration of the free enzyme (the second step of the catalytic mechanism) is slow. This becomes a toxicological problem only at doses of the epoxide that titrate the enzyme out. Our genotoxicity work s…