615 research outputs found
Therapeutic Options in Hereditary Optic Neuropathies
Options for the effective treatment of hereditary optic neuropathies have been a long time coming. The successful launch of the antioxidant idebenone for Leber’s Hereditary Optic Neuropathy (LHON), followed by its introduction into clinical practice across Europe, was an important step forward. Nevertheless, other options, especially for a variety of mitochondrial optic neuropathies such as dominant optic atrophy (DOA), are needed, and a number of pharmaceutical agents, acting on different molecular pathways, are currently under development. These include gene therapy, which has reached Phase III development for LHON, but is expected to be developed also for DOA, whilst most of the other agents (other antioxidants, anti-apoptotic drugs, activators of mitobiogenesis, etc.) are almost all at Phase II or at preclinical stage of research. Here, we review proposed target mechanisms, preclinical evidence, available clinical trials with primary endpoints and results, of a wide range of tested molecules, to give an overview of the field, also providing the landscape of future scenarios, including gene therapy, gene editing, and reproductive options to prevent transmission of mitochondrial DNA mutations
Effects of Serenoa repens, selenium and lycopene (Profluss®) on chronic inflammation associated with benign prostatic hyperplasia: results of "FLOG" (Flogosis and Profluss in Prostatic and Genital Disease), a multicentre Italian study.
Objective To evaluate the efficacy of Profluss® on prostatic chronic inflammation (PCI). Materials and Methods We prospectively enrolled 168 subjects affected by LUTS due to bladder outlet obstruction submitted to 12 cores prostatic biopsy for suspected prostate cancer + 2 cores collected for PCI valuation. First group consisted of 108 subjects, with histological diagnosis of PCI associated with BPH and high grade PIN and/or ASAP, randomly assigned to 1:1 ratio to daily Profluss® (group I) for 6 months or to control group (group Ic). Second group consisted of 60 subjects, with histological diagnosis of BPH, randomly assigned to 1:1 ratio to daily Profluss® + α-blockers treatment (group II) for 3 months or to control group (group IIc). After 6 months first group underwent 24 cores prostatic re-biopsy + 2 cores for PCI while after 3 months second group underwent two-cores prostatic for PCI. Specimens were evaluated for changes in inflammation parameters and for density of T-cells (CD3, CD8), B-cells (CD20) and macrophages (CD68). Results At follow-up there were statistical significant reductions of extension and grading of flogosis, mean values of CD20, CD3, CD68 and mean PSA value in group I compared to Ic, while extension and grading of flogosis in group II were inferior to IIc but not statistical significant. A statistically significant reduction in the density of CD20, CD3, CD68, CD8 was demonstrated in group II in respect to control IIc. Conclusions Serenoa repens+Selenium+Lycopene may have an anti-inflammatory activity that could be of interest in the treatment of PCI in BPH and/or PIN/ASAP patients
Effects of Serenoa Repens, Selenium and Lycopene (Profluss®) on chronic inflammation associated with Benign Prostatic Hyperplasia: results of "FLOG" (Flogosis and Profluss in Prostatic and Genital Disease), a multicentre Italian study
Objective To evaluate the efficacy of Profluss® on prostatic chronic inflammation (PCI). Materials and Methods We prospectively enrolled 168 subjects affected by LUTS due to bladder outlet obstruction submitted to 12 cores prostatic biopsy for suspected prostate cancer + 2 cores collected for PCI valuation. First group consisted of 108 subjects, with histological diagnosis of PCI associated with BPH and high grade PIN and/or ASAP, randomly assigned to 1:1 ratio to daily Profluss® (group I) for 6 months or to control group (group Ic). Second group consisted of 60 subjects, with histological diagnosis of BPH, randomly assigned to 1:1 ratio to daily Profluss® + α-blockers treatment (group II) for 3 months or to control group (group IIc). After 6 months first group underwent 24 cores prostatic re-biopsy + 2 cores for PCI while after 3 months second group underwent two-cores prostatic for PCI. Specimens were evaluated for changes in inflammation parameters and for density of T-cells (CD3, CD8), B-cells (CD20) and macrophages (CD68). Results At follow-up there were statistical significant reductions of extension and grading of flogosis, mean values of CD20, CD3, CD68 and mean PSA value in group I compared to Ic, while extension and grading of flogosis in group II were inferior to IIc but not statistical significant. A statistically significant reduction in the density of CD20, CD3, CD68, CD8 was demonstrated in group II in respect to control IIc. Conclusions Serenoa repens+Selenium+Lycopene may have an anti-inflammatory activity that could be of interest in the treatment of PCI in BPH and/or PIN/ASAP patients
OpenSeesPy-based web application for pushover curve computation of RC bridge piers subject to arbitrarily non-uniform corrosion patterns
Existing reinforced concrete (RC) bridge piers are often subject to complex spatially non-uniform steel corrosion patterns typically due to water percolation and exposition to environmental agents. This produces degradation of strength and ductility of the pier, which may significantly influence the seismic performances of bridges. The computation of pushover curves of corroded RC piers can be carried out by fiber-beam-column elements combined with suitable degradation laws for the uniaxial materials. For this purpose, a multi-level fiber-based modeling procedure is proposed based on a partition of the pier into zones characterized by different cross-sections with fiber discretizations reproducing the sectional deterioration pattern.
A web application based on OpenSeesPy is defined to implement this procedure. This includes an interface developed by React JS and Boostrap V5 and an APIs layer based on the Flask framework. Through the interface, users can insert the parameters needed for the structural response simulation, which is, then, performed by employing the numerical procedure developed in Python. At the end of the computation, users can visualize and download the results or vary the input parameters to perform new simulations. The web application runs in a Docker container, making it easy to deploy on cloud platforms or on-premises solutions.
Numerical simulations of real specimens affected by material deterioration are performed
Progressive ataxia with oculo-palatal tremor and optic atrophy
The final publication is available at Springer via doi: 10.​1007/​s00415-013-7136-
SPADA: A project to study the effectiveness of shielding materials in space
The SPADA (SPAce Dosimetry for Astronauts) project is a part of an extensive teamwork that aims to optimize shielding solutions against space radiation. Shielding is indeed an irreplaceable tool to reduce exposure of crews of future Moon and Mars missions. We concentrated our studies on two flexible materials, Kevlar Rďż˝ and Nextel R,ďż˝ because of their ability to protect human space infrastructures
from micrometeoroids. We measured radiation hardness of these shielding materials and compared to polyethylene, generally acknowledged as the most effective space radiation shield with practical applications in spacecraft. Both flight test (on the International Space Station and on the Russian FOTON M3 rocket), with passive dosimeters and accelerator-based experiments have been performed. Accelerator tests using high-energy Fe ions have demonstrated that Kevlar is almost as effective as polyethylene in shielding heavy ions, while Nextel is a poor shield against high-charge and -energy particles. Preliminary results from spaceflight, however, show that for the radiation environment in low-Earth orbit, dominated by trapped protons, thin shields of Kevlar and Nextel provide limited reduction
Comparison between in vitro chemical and ex vivo biological assays to evaluate antioxidant capacity of botanical extracts
The anti-oxidative activity of plant-derived extracts is well-known and confers health-promoting effects on functional foods and food supplements. Aim of this work is to evaluate the capability of two different assays to predict the real biological antioxidant efficiency. At this purpose, extracts from five different plant-derived matrices and commercial purified phytochemicals were analyzed for their anti-oxidative properties by using well-standardized in vitro chemical method (TEAC) and an ex vivo biological assay. The biological assay, a cellular membrane system obtained from erythrocytes of healthy volunteers, is based on the capability of phytochemicals treatment to prevent membrane lipid peroxidation under oxidative stress by UV-B radiation. Plant extracts naturally rich in phenols with different structure and purified phytochemicals showed different in vitro and ex vivo antioxidant capacities. A high correlation between phenolic contents of the plant-derived extracts and their ability to prevent oxidative injuries in a biological system was found, thus underlying the relevance of this class of metabolites in preventing oxidative stress. On the other hand, a low correlation between the antioxidant capacities was shown between in vitro and ex vivo antioxidant assay. Moreover, data presented in this work show how food complex matrices are more effective in preventing oxidative damages at biological level than pure phytochemicals, even if for these latter, the antioxidant activity was generally higher than that observed for food complex matrices
Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer's disease
BACKGROUND:
Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD.
METHODS:
We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid \u3b242 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid \u3b242 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm.
RESULTS:
Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls.
CONCLUSIONS:
The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD
Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case-control study.
Published onlineJournal ArticleMulticenter StudyObservational StudyResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from BMJ Publishing Group via the DOI in this record.OBJECTIVES: To compare the clinical effectiveness of the intravesical administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus current standard management in adult women with recurrent urinary tract infections (RUTIs). SETTING: A European Union-based multicentre, retrospective nested case-control study. PARTICIPANTS: 276 adult women treated for RUTIs starting from 2009 to 2013. INTERVENTIONS: Patients treated with either intravesical administration of HA+CS or standard of care (antimicrobial/immunoactive prophylaxis/probiotics/cranberry). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was occurrence of bacteriologically confirmed recurrence within 12 months. Secondary outcomes were time to recurrence, total number of recurrences, health-related quality of life and healthcare resource consumption. Crude and adjusted results for unbalanced characteristics are presented. RESULTS: 181 patients treated with HA+CS and 95 patients treated with standard of care from 7 centres were included. The crude and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and 0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to 1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)). The benefit of intravesical HA+CS therapy improves when the number of instillations is ≥ 5. CONCLUSIONS: Our results show that bladder instillations of combined HA+CS reduce the risk of bacteriologically confirmed recurrences compared with the current standard management of RUTIs. Total incidence rates and hazard rates were instead non-significantly different between the 2 groups after adjusting for unbalanced factors. In contrast to what happens with antibiotic prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over time. TRIAL REGISTRATION NUMBER: NCT02016118.This study was funded by an unrestricted grant from the TETI Association—study group for urogenital diseases. Members of the association were involved in the data collection and revised the manuscript
Serenoa repens, lycopene and selenium vs tamsulosin in the treatment of LUTS/BPH: An Italian multicenter randomized comparative study between single or combination therapies (Procomb Study)
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