Publications by authors named "Maria Tiziana Corasaniti"

72 Publications

New trends in pharmacological control of neuropsychiatric symptoms of dementia.

Curr Opin Pharmacol 2021 Oct 8;61:69-76. Epub 2021 Oct 8.

Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy. Electronic address:

Abnormal neuronal and synaptic plasticity occurs in Alzheimer's disease (AD) and depression. The latter, particularly late-life, has been recognized as fundamental in the identification of at-risk prodromal stages of AD. The lack of disease-modifying drugs and the off-label use of antipsychotics and antidepressants for neuropsychiatric symptoms (NPSs) have caused a season of therapeutic inappropriateness. To date, the wealth of clinical trials investigating drugs, diverse for structure and mechanism of action, has failed to provide a cure for all the spectrums of NPSs. Psychedelics in microdosing afford promotion of neurogenesis and synaptic plasticity and, recently, have been considered a revolution for the management of depression endowed with faster action and an improved side effect profile than antidepressants. In the current scenario, therefore, the rapid-acting antidepressant esketamine could represent the first-in-class for treatment of NPSs, and this deserves to be demonstrated with an open-label clinical trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.coph.2021.09.002DOI Listing
October 2021

Exploitation of Thermal Sensitivity and Hyperalgesia in a Mouse Model of Dystonia.

Life (Basel) 2021 Sep 19;11(9). Epub 2021 Sep 19.

Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.

Neuropathic pain is characterized by mechanical allodynia and thermal hyperalgesia to heat, and it affects some 20% of European population. Patients suffering from several neurologic diseases experience neuropathic pain, often finding no relief in therapy. Transgenic mice expressing the gene encoding the human mutant (hMT) or the human wild-type (hWT) torsin A represent a preclinical model of DYT1 dystonia which is the most common form of early-onset inherited dystonia. Baseline thermal sensitivity and hyperalgesia to heat have never been studied in models of dystonia. Therefore, the aim of this research has been to characterize thermal sensitivity in baseline conditions and hyperalgesia to heat after the induction of neuropathic pain through the spinal nerve ligation (SNL) model in mice overexpressing human wild-type and mutated torsin A in comparison to non-transgenic C57BL/6 mice. According to our results, the paw withdrawal latency time to heat in the Hargreaves' test is significantly lower in the hMT mice (Kruskal-Wallis test = 6.933; = 0.0312*; hMT vs. hWT = 0.0317*). On the other hand, no significant differences in SNL-induced thermal hyperalgesia was found among the three strains (Friedman test = 4.933; = 0.1019). Future studies are needed to better understand the role of torsin A in sensory processing of heat stimuli.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/life11090985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468866PMC
September 2021

Bergamot rehabilitation AgaINst agitation in dementia (BRAINAID): Study protocol for a randomized, double-blind, placebo-controlled trial to assess the efficacy of furocoumarin-free bergamot loaded in a nanotechnology-based delivery system of the essential oil in the treatment of agitation in elderly affected by severe dementia.

Phytother Res 2021 Aug 26. Epub 2021 Aug 26.

Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health Science and Nutrition, University of Calabria, Rende, Italy.

Pain is underdiagnosed and often not adequately treated, contributing to behavioral and psychological symptoms of dementia (BPSD). BPSD are treated with atypical antipsychotics that are associated with severe cerebrocardiovascular effects. Interestingly, treatment of pain may reduce agitation. Research is focusing on nonpharmacological treatment, such as aromatherapy, for pain and BPSD in dementia. This clinical study will assess the effect on agitation in severely demented elderly of BEO loaded in a nanotechnological odorless cream indistinguishable from placebo. This is a protocol for a randomized, double-blind, placebo-controlled trial (NCT04321889). A total of 134 patients aged ≥65 years with severe dementia (mini-mental state examination <12) will be recruited and randomly allocated 1:1 to either BEO or placebo group. After baseline screening, BEO (80 mg) cream or placebo cream will be trans-dermally applied on both arms twice a day for 4 weeks with a 4-week follow-up period. The effect on agitation will be the primary endpoint. Any adverse events will be reported. A double-blind, clinical trial evaluating efficacy and safety of an essential oil endowed with strong analgesic properties has never been carried out before. This study could form the basis for a safer and more effective treatment of BPSD in severe dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ptr.7223DOI Listing
August 2021

Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy.

J Headache Pain 2021 Jul 30;22(1):87. Epub 2021 Jul 30.

Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Rende, Italy.

Background: the interest of clinical reaseach in polymorphisms and epigenetics in migraine has been growing over the years. Due to the new era of preventative migraine treatment opened by monoclonal antibodies (mAbs) targeting the signaling of the calcitonin-gene related peptide (CGRP), the present systematic review aims at identifying genetic variants occurring along the CGRP pathway and at verifying whether these can affect the clinical features and the course of disease and the responsiveness of patients to therapy.

Methods: the literature search has been conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science, the Human Genome Epidemiology (HuGE) Published Literature database (Public Health Genomics Knowledge Base) and Clinicaltrials.gov from database inception until April 1, 2021. The process of identification and selection of the studies included in the analysis has followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria for systematic reviews and meta-analyses and the guidance from the Human Genome Epidemiology Network for reporting gene-disease associations.

Results: the search has retrieved 800 results, among which only 7 studies have met the eligibility criteria for inclusion in the analysis. The latter are case-control studies of genetic association and an exploratory analysis and two polymorphisms have been detected as the most recurring: the rs3781719 (T > C) of the CALC A gene encoding CGRP and the rs7590387 of the gene encoding the receptor activity-modifying protein (RAMP) 1 (C > G). Only one study assessing the methylation pattern with regard to CGRP pathway has been found from the search. No genetic association studies investigating the possible effect of genetic variants affecting CGRP signaling on the responsiveness to the most recent pharmacological approaches, i.e. anti-CGRP(R) mAbs, gepants and ditans, have been published. According to the Human Genome Epidemiology (HuGE) systematic reviews and meta-analyses risk-of-bias score for genetic association studies, the heterogeneity between and across studies and the small sample size do not allow to draw conclusions and prompt future studies.

Conclusions: adequately powered, good quality genetic association studies are needed to understand the impact of genetic variants affecting the pathway of CGRP on migraine susceptibility and clinical manifestation and to predict the response to therapy in terms of efficacy and safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-021-01295-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325208PMC
July 2021

Editorial: "Novel Pain Therapeutics: From Basic Research to Clinical Translation and Rehabilitation".

Front Pharmacol 2021 14;12:681422. Epub 2021 Apr 14.

Pharmacotechnology Documentation and Transfer Unit, Section of Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.681422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080444PMC
April 2021

Development and Translation of NanoBEO, a Nanotechnology-Based Delivery System of Bergamot Essential Oil Deprived of Furocumarins, in the Control of Agitation in Severe Dementia.

Pharmaceutics 2021 Mar 12;13(3). Epub 2021 Mar 12.

Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.

Dementia is one of the most common causes of disability worldwide characterized by memory loss, cognitive impairment, and behavioral and psychological symptoms (BPSD), including agitation. Treatment of the latter consists of the off-label use of harmful atypical antipsychotics, though a significant reduction is afforded by pain control. The use of an essential oil endowed with analgesic properties and devoid of toxicity would represent an important option for the management of agitation in dementia. Therefore, the aim of this study was to engineer a nanotechnology delivery system based on solid lipid nanoparticles loaded with bergamot essential oil (BEO) and devised in the pharmaceutical form of an odorless cream (NanoBEO) to confirm its analgesic efficacy for further development and application to control agitation in dementia. BEO has proven strong antinociceptive and anti-allodynic properties and, in its bergapten-free form, it is completely devoid of phototoxicity. NanoBEO has been studied in vivo confirming the previously reported analgesic activity of BEO to which is now added its anti-itching properties. Due to the nanotechnology delivery system, the stability of titrated BEO components is guaranteed. Finally, the latter invention, currently under patent consideration, is smell-devoid allowing efficacy and safety to be established in double-blind clinical trials; until now the latter studies have been impeded in aromatherapy by the strong odor of essential oils. A clinical trial NCT04321889 has been designed to provide information about the efficacy and safety of NanoBEO on agitation and pain in patients suffering from severe dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics13030379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999378PMC
March 2021

Efficacy of Essential Oils in Pain: A Systematic Review and Meta-Analysis of Preclinical Evidence.

Front Pharmacol 2021 1;12:640128. Epub 2021 Mar 1.

Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

The demand for essential oils (EOs) has been steadily growing over the years. This is mirrored by a substantial increase in research concerned with EOs also in the field of inflammatory and neuropathic pain. The purpose of this present systematic review and meta-analysis is to investigate the preclinical evidence in favor of the working hypothesis of the analgesic properties of EOs, elucidating whether there is a consistent rational basis for translation into clinical settings. A literature search has been conducted on databases relevant for medical scientific literature, i.e., PubMed/MEDLINE, Scopus, and Web of Science from database inception until November 2, 2020, following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria for systematic reviews and meta-analyses. The search was conducted in order to answer the following PICOS (participants/population, interventions, comparisons, outcomes, and study design) question: are EOs efficacious in reducing acute nociceptive pain and/or neuropathic pain in mice experimental models? The search retrieved 2,491 records, leaving 954 studies to screen after the removal of duplicates. The title and abstract of all 954 studies were screened, which left 127 records to evaluate in full text. Of these, 30 articles were eligible for inclusion. Most studies (27) assessed the analgesic properties of EOs on acute nociceptive pain models, e.g. the acetic acid writhings test, the formalin test, and the hot plate test. Unfortunately, efficacy in neuropathic pain models, which are a more suitable model for human conditions of chronic pain, had fewer results (only three studies). Moreover, some methodologies raised concerns in terms of the risk of bias. Therefore, EOs with proven efficacy in both types of pain were corroborated by methodologically consistent studies, like the EO of bergamot, which should be studied in clinical trials to enhance the translational impact of preclinical modeling on clinical pain research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.640128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957371PMC
March 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A.

Life (Basel) 2021 Jan 12;11(1). Epub 2021 Jan 12.

School of Hospital Pharmacy, University "Magna Graecia" of Catanzaro and Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.

Background: DYT1 dystonia is the most common form of early-onset inherited dystonia, which is caused by mutation of torsin A (TA) belonging to the "ATPases associated with a variety of cellular activities" (AAA + ATPase). Dystonia is often accompanied by pain, and neuropathic pain can be associated to peripherally induced movement disorder and dystonia. However, no evidence exists on the effect of gabapentin in mice subjected to neuropathic pain model overexpressing human normal or mutated TA.

Methods: Mice subjected to L5 spinal nerve ligation (SNL) develop mechanical allodynia and upregulation of the α2δ-1 L-type calcium channel subunit, forming a validated experimental model of neuropathic pain. Under these experimental conditions, TA is expressed in dorsal horn neurons and astrocytes and colocalizes with α2δ-1. Similar to this subunit, TA is overexpressed in dorsal horn 7 days after SNL. This model has been used to investigate (1) basal mechanical sensitivity; (2) neuropathic pain phases; and (3) the effect of gabapentin, an α2δ-1 ligand used against neuropathic pain, in non-transgenic (NT) C57BL/6 mice and in mice overexpressing human wild-type (hWT) or mutant (hMT) TA.

Results: In comparison to non-transgenic mice, the threshold for mechanical sensitivity in hWT or hMT does not differ (Kruskal-Wallis test = 1.478; = 0.4777, although, in the latter animals, neuropathic pain recovery phase is delayed. Interestingly, gabapentin (100 mg/Kg) reduces allodynia at its peak (occurring between post-operative day 7 and day 10) but not in the phase of recovery.

Conclusions: These data lend support to the investigation on the role of TA in the molecular machinery engaged during neuropathic pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/life11010041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826569PMC
January 2021

Opioids in Post-stroke Pain: A Systematic Review and Meta-Analysis.

Front Pharmacol 2020 27;11:587050. Epub 2020 Nov 27.

Regional Center for Serious Brain Injuries, S. Anna Institute, Crotone, Italy.

Post-stroke pain is one of the most common of stroke, which stands among the leading causes of death and adult-acquired disability worldwide. The role and clinical efficacy of opioids in post-stroke pain syndromes is still debated. Due to the important gap in knowledge on the management of post-stroke pain, this systematic review aimed at assessing the efficacy of opioids in post-stroke pain syndromes. A literature search was conducted on databases relevant for medical scientific literature, i.e. PubMed/MEDLINE, Scopus, Web of Science and Cochrane Library databases from databases inception until August 31, 2020 for clinical trials assessing the effects of opioids and opioid antagonists on pain reduction and pain related symptoms in patients with post-stroke pain syndromes. Studies assessing the effects of other medications (e.g., tricyclic antidepressant, pregabalin) or non - pharmacological management strategies (e.g., neurostimulation techniques) were excluded. The selected studies have been subjected to examination of the risk of bias. The literature search retrieved 83,435 results. After duplicates removal, 34,285 articles were title and abstract screened. 25 full texts were assessed and 8 articles were identified to be eligible for inclusion in the qualitative summary and narrative analysis, of which three were placebo-controlled and two were dose-response. Among placebo-controlled studies, two evaluated the analgesic effect of morphine and one assessed the effects of the opioid antagonist naloxone on patients with central post-stroke pain. With regard to dose-response studies, both were on patients with central post-stroke pain, one assessing the efficacy of levorphanol, and the other on naloxone. Seven out of eight included studies showed an overall slight analgesic effect of opioids, with less consistent effects on other pain-related symptoms (e.g., mood, quality of life). The randomized controlled trials were subjected to meta-analysis and rating of the quality of evidence for the two outcomes considered according to GRADE (Grading of Recommendations, Assessment, Development and Evaluations) system. The overall results are inconclusive because of the small number of studies and of patients. The limited number of the included studies and their heterogeneity in terms of study design do not support the efficacy of opioids in post-stroke pain and in pain-related outcomes. Large double-blind randomized clinical trials with objective assessment of pain and related symptoms are needed to further investigate this topic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.587050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793939PMC
November 2020

Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma.

Nutrients 2020 Oct 16;12(10). Epub 2020 Oct 16.

Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.

Glaucoma, a leading cause of irreversible blindness worldwide, is an optic neuropathy characterized by the progressive death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is recognized as the main risk factor. Despite effective IOP-lowering therapies, the disease progresses in a significant number of patients. Therefore, alternative IOP-independent strategies aiming at halting or delaying RGC degeneration is the current therapeutic challenge for glaucoma management. Here, we review the literature on the neuroprotective activities, and the underlying mechanisms, of natural compounds and dietary supplements in experimental and clinical glaucoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12103158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602834PMC
October 2020

Effects of the autophagy modulators d-limonene and chloroquine on vimentin levels in SH-SY5Y cells.

Biochem Biophys Res Commun 2020 12 26;533(4):764-769. Epub 2020 Sep 26.

Department of Health Sciences, University "Magna Graecia" of Catanzaro, Campus Universitario "Salvatore Venuta", Viale Europa, 88100, Catanzaro, Italy. Electronic address:

The molecular target and mechanism by which d-limonene induces LC3 lipidation and autophagosome formation remain elusive. Here, we report that this monoterpene rapidly enhances Ca levels in SH-SY5Y cells; yet this effect does not lead to calpain- or caspase-mediated proteolysis of α-spectrin, nor calpain activity is required for the established enhancement of LC3-II levels by d-limonene. However, d-limonene rapidly reduced vimentin levels, an unexpected effect also induced by the autophagy inhibitor chloroquine (CQ). The magnitude of vimentin reduction parallels accumulation of LC3-II caused by a brief incubation with d-limonene or CQ. For longer exposure (48 h), d-limonene does not reduce vimentin, nor it increases LC3-II levels; conversely, a clear reduction of vimentin along with a massive accumulation of LC3-II is evident in cells treated with CQ. Vimentin participates in organelle positioning and in other cellular processes that have linked this intermediate filament protein to various diseases, including cancer, inflammatory and autoimmune disorders, and to virus replication and internalization. Our findings suggest an inverse relationship between vimentin reduction and LC3-II accumulation, whose causal link needs to be examined. Further experiments are needed to dissect the role of vimentin reduction in the mechanisms through which CQ impairs fusion of autophagosome with lysosomes as well as in other effects of this drug.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2020.09.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518972PMC
December 2020

Evidence on the neuroprotective properties of brimonidine in glaucoma.

Prog Brain Res 2020 6;257:155-166. Epub 2020 Aug 6.

School of Hospital Pharmacy, University "Magna Graecia" of Catanzaro and Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Background: glaucoma is the leading cause of irreversible blindness all over the world. The degree of visual field loss accounts for the severity of the disease and represents the main clinical outcome of treatment for patients affected by glaucoma. The α2 agonists, like brimonidine, emerged in the 1960s as topical ophthalmologic treatment. Their neuroprotective mechanism in glaucoma is still debated, ranging from effect on extracellular glutamate, to ocular hypotension and blood flow.

Objectives: this systematic review and meta-analysis aims at assessing the efficacy of brimonidine on visual field deterioration during glaucoma through the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) approach. Databases consulted: the literature search has been performed on PubMed, MEDLINE, ClinicalTrials.gov and Scopus up to June 10th, 2020. Study eligibility criteria, participants, and interventions: clinical trials assessing the effects of brimonidine on visual field in patients with glaucoma. Study appraisal: the eligibility of the studies has been assessed by two independent authors and the selection has followed the PRISMA flow diagram. The retrieved results have been subjected to risk of bias evaluation.

Results: the search of literature has retrieved 418 papers, among which 5 are eligible for inclusion in the qualitative analysis. All the studies present high heterogeneity, therefore meta-analysis has not been possible. The results obtained suggest that brimonidine improves visual field, but the design of the clinical trials rises some concerns in terms of risk of bias.

Conclusions: the evidence of neuroprotective effect of brimonidine is inconclusive and needs stronger support. Large double-blind randomized clinical trials are necessary to strengthen this evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/bs.pbr.2020.07.008DOI Listing
August 2020

Impact of nutraceuticals on glaucoma: A systematic review.

Prog Brain Res 2020 18;257:141-154. Epub 2020 Aug 18.

Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, Rende, Italy.

Background: glaucoma is a remarkable social issue being the leading cause of irreversible blindness worldwide. It is a progressive neuropathy characterized by the death of the retinal ganglion cells, of which the most important risk factor is represented by the increase of intraocular pressure (IOP). The role of nutraceutical supplementations with anti-oxidant activity has been extensively tested in preclinical models of glaucoma. The clinical efficacy of nutraceuticals in glaucoma is still controversial.

Objectives: the aim of this systematic review is to assess the efficacy of nutraceuticals with anti-oxidant activity in glaucoma through the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) rigorous criteria.

Data Sources: the literature search has been performed on the electronic databases currently recognized of most relevance for medical scientific literature, i.e. PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials (CENTRAL) with access to EMBASE, ClinicalTrials.gov and Scopus. The date of last search is April 8th, 2020. Study eligibility criteria, participants, and interventions: prospective randomized clinical trials assessing the effects of nutraceuticals and anti-oxidants on IOP and/or visual field in patients with glaucoma. The eligible papers must be published in English and available in full text.

Study Appraisal And Synthesis Methods: the evaluation of the eligibility of the studies has been carried out independently by two authors. The selection process has followed the PRISMA flow diagram, assessing the quality of the body of evidence and the risk of bias.

Results: the search of literature has retrieved 1615 papers and 2 clinical trials with results, among which only 6 are eligible for inclusion in the present systematic review to address the preset participants, interventions, comparisons, outcomes and study design (PICOS) "are the nutraceuticals effective in glaucoma?". In 5 out of 6 studies the nutraceutical supplementation is effective in providing additional decrease of IOP to current usual therapy, without the occurrence of side effects. However, all the studies present high heterogeneity and some concerns in terms of risk of bias, apart from one trial for which the risk of bias is low.

Conclusions: the evidence of effectiveness of nutraceutical formulations is still uncertain and inconclusive. Therefore, large double-blind randomized clinical trials with adequate design, methodology and statistical power are needed to support the use of nutraceuticals in glaucoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/bs.pbr.2020.07.014DOI Listing
August 2020

Effects of caloric restriction on retinal aging and neurodegeneration.

Prog Brain Res 2020 18;256(1):189-207. Epub 2020 Aug 18.

Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy. Electronic address:

Glaucoma is the most common neurodegenerative cause of irreversible blindness worldwide. Restricted caloric regimens are an attractive approach for delaying the progression of neurodegenerative diseases. Here we review the current literature on the effects of caloric restriction on retinal neurons, under physiological and pathological conditions. We focused on autophagy as one of the mechanisms modulated by restricted caloric regimens and involved in the death of retinal ganglion cells (RGCs) over the course of glaucoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/bs.pbr.2020.07.005DOI Listing
July 2021

Pattern of treatment of behavioural and psychological symptoms of dementia and pain: evidence on pharmacoutilization from a large real-world sample and from a centre for cognitive disturbances and dementia.

Eur J Clin Pharmacol 2021 Feb 15;77(2):241-249. Epub 2020 Sep 15.

Department of Health Science, University Magna Graecia, 88100, Catanzaro, Italy.

Purpose: Data concerning the number of diagnoses and of the drugs prescribed to patients affected by dementia are still scarce. Here we test whether or not (1) prescription of symptomatic drugs against Alzheimer's disease (AD) may approximate the number of patients affected by dementia in Italy and (2) adherence to this treatment affects the pattern of prescription of drugs (i.e. antipsychotics and antidepressants) for behavioural and psychological symptoms of dementia (BPSD) and the previously reported limited prescription of analgesics.

Methods: This retrospective observational study concerns 84,235 subjects older than 60 years and registered in the provincial prescription database of the health district of Cosenza accounting for a population of 298,000 inhabitants. The prescribing pattern of antipsychotics, antidepressants, and analgesics has been investigated in patients receiving concurrent prescriptions of acetylcholinesterase inhibitors (AChEI) and/or memantine. Data from a single centre for cognitive disturbances and dementia (CDCD) in the same health district were used to explore at which stage dementia was diagnosed. The study was approved by Calabria Region Ethical Committee no. 31/2017 and registered on October 31, 2017.

Results: The data show that 859 patients are treated with AChEI and/or memantine; 420 patients (48.89%) receive at least 80% of the recommended medications. CDCD data indicate a delay in dementia diagnosis, which often was made when the patients were moderately to severely demented (Mini Mental State Examination, MMSE ≤ 20). Adherence did not influence prescription of most of the drugs explored, but use of non-steroidal anti-inflammatory drugs was higher in non-adherent patients. Antipsychotics and antidepressants are frequently used (20.61-20.71% and 42.37-51.43%, respectively), and this, at least in part, might stem from the observed under-treatment of chronic pain (opioids are prescribed in the 4.76% and 12.46% of adherent and non-adherent patients and gabapentin and pregabalin are used in the 4.29% and 4.07% of adherent and non-adherent patients respectively), resulting in more frequent BPSD. 16.43% of patients receive antipsychotics for longer than 6-12 weeks.

Conclusion: This 2-year period study, including a wide cohort of community demented patients, shows that dementia is diagnosed late and that prevalence of BPSD prescriptions is high and not impacted by adherence to anti-dementia drugs. The rate of prescription of potentially harmful antipsychotics and antidepressants appears to be high though whether the concomitantly observed limited prescription of analgesics might be a contributing factor needs to be further investigated. Our data support the development of strategies to improve the management of BPSD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00228-020-02995-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803691PMC
February 2021

Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance.

Life (Basel) 2020 Jul 4;10(7). Epub 2020 Jul 4.

School of Hospital Pharmacy, University "Magna Graecia" of Catanzaro and Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.

The therapeutic efficacy of a drug or its unexpected unwanted side effects may depend on the concurrent use of a medicinal plant. In particular, constituents in the medicinal plant extracts may influence drug bioavailability, metabolism and half-life, leading to drug toxicity or failure to obtain a therapeutic response. This narrative review focuses on clinical studies improving knowledge on the ability of selected herbal medicines to influence the pharmacokinetics of co-administered drugs. Moreover, in vitro studies are useful to anticipate potential herbal medicine-drug interactions. In particular, they help to elucidate the cellular target (metabolic or transporter protein) and the mechanism (induction or inhibition) by which a single constituent of the herbal medicine acts. The authors highlight the difficulties in predicting herbal-drug interactions from in vitro data where high concentrations of extracts or their constituents are used and pharmacokinetics are missed. Moreover, the difficulty to compare results from human studies where different kinds of herbal extracts are used is discussed. The herbal medicines discussed are among the best sellers and they are reported in the "Herbal Medicines for Human Use" section of the European Medicinal Agency (EMA).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/life10070106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400069PMC
July 2020

Effects of Aging on Formalin-Induced Pain Behavior and Analgesic Activity of Gabapentin in C57BL/6 Mice.

Front Pharmacol 2020 8;11:663. Epub 2020 May 8.

Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Improved living conditions have induced an increase of lifespan often accompanied by comorbidities, responsible for pain, and by cognitive impairment and dementia, impairing communication capabilities. In most cases, the elderly do not receive pain relief because of underdiagnosis and of aging-induced changes of systems affecting nociceptive response. Unrelieved pain is involved in the development of behavioral symptoms, as agitation, representing a difficult challenge in this fragile population. Aged C57BL/6 mice and amyloid precursor protein (APP) mice display behavioral disturbances that mimic behavioral and psychological symptoms of dementia (BPSD). Therefore, this original study focuses on the influence of aging on nociception to provide insight into the occurrence of BPSD. We have investigated how aging can affect nociception after formalin administration and gabapentin effect in C57BL/6 mice, since it represents one of the treatments of choice for chronic neuropathic pain. Based on our results, changes of nociceptive behavior in response to an algogen stimulus occur during aging. Formalin-induced behavioral pattern in older C57BL/6 mice presents a temporal shift and an increase in the peak amplitudes. Our data show that the effectiveness of gabapentin is influenced by the age of the animal; though preliminary, the latter provide evidence upon which formalin test induced long-lasting mechanical allodynia might be a reliable as rapid and viable persistent pain model. The disclosed differences in effectiveness of gabapentin according to age can form the rational basis to deepen the study of pain treatment in the elderly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.00663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227482PMC
May 2020

Role of 5-HT1A Receptor in the Anxiolytic-Relaxant Effects of Bergamot Essential Oil in Rodent.

Int J Mol Sci 2020 Apr 9;21(7). Epub 2020 Apr 9.

Preclinical and Translational Pharmacology, Department of Pharmacy, Health Science and Nutrition, University of Calabria, 87036 Rende, Italy.

The essential oil obtained by the fresh fruit of Risso et Poiteau is used worldwide in aromatherapy to reduce pain, facilitate sleep induction, and/or minimize the effects of stress-induced anxiety. Preclinical pharmacological data demonstrate that bergamot essential oil (BEO) modulates specific neurotransmissions and shows an anxiolytic-relaxant effect not superimposable to that of the benzodiazepine diazepam, suggesting that neurotransmissions, other than GABAergic, could be involved. Several studies on essential oils indicate a role for serotonergic (5-HT) neurotransmission in anxiety. Interestingly, among serotonergic receptors, the 5-HT1A subtype seems to play a key role in the control of anxiety. Here, we report that modulation of the 5-HT1A receptor by selective agonist ((±)8-OH-DPAT) or antagonist (WAY-100635) may influence some of the anxiolytic-relaxant effects of BEO in Open Field and Elevated Plus Maze tests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21072597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177770PMC
April 2020

The Role of Autophagy in Glaucomatous Optic Neuropathy.

Front Cell Dev Biol 2020 4;8:121. Epub 2020 Mar 4.

Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, Rende, Italy.

Autophagy is a conserved lysosomal-dependent pathway responsible for the degradation of cytoplasmic macromolecules. Based on the mechanism of cargo delivery to lysosomes, mammalian cells can undergo micro, macro, and chaperone-mediated autophagy. Other than physiological turnover of proteins and organelles, autophagy regulates cellular adaptation to different metabolic states and stressful conditions by allowing cellular survival or, when overactivated, participating to cell death. Due to their structure and function, neurons are highly dependent on autophagy efficiency and dysfunction of the pathway has been associated with neurodegenerative disorders. Glaucomatous optic neuropathies, a leading cause of blindness, are characterized by the progressive loss of a selective population of retinal neurons, i.e., the retinal ganglion cells (RGCs). Here we review the current literature on the role of autophagy in the pathogenic process that leads to the degeneration of RGC in various experimental models of glaucoma exploring the modulation of the pathway as a potential therapeutic intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2020.00121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066980PMC
March 2020

Pattern of triptans use: a retrospective prescription study in Calabria, Italy.

Neural Regen Res 2020 Jul;15(7):1340-1343

School of Hospital Pharmacy; Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Triptans are 5-hydroxytryptamine 1B/1D receptor agonists used in moderate to severe migraine attacks as first line when non-specific, symptomatic, nonsteroidal anti-inflammatory drugs are not effective. To gain insight in the treatment of migraine in the regional context, this retrospective (from January to August of the years 2017 and 2018) study aimed at monitoring the use of triptans approved by the regional health authority in Calabria. The data demonstrate that the overall treatment of migraine with triptans in the different provinces of Calabria falls in the average regional prescription/dispensation. Interestingly, Crotone showed a trend to an increased amount of defined daily dose/1000 inhabitants per day. The present analysis might stand for homogeneity of treatment of migraineurs in Calabria and highlights the need for better understanding the apparent differences in the local pattern of almotriptan use to improve the appropriateness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1673-5374.272630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047800PMC
July 2020

Azithromycin Affords Neuroprotection in Rat Undergone Transient Focal Cerebral Ischemia.

Front Neurosci 2019 26;13:1256. Epub 2019 Nov 26.

Section of Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.

Repurposing existing drugs represents a promising approach for successful development of acute stroke therapies. In this context, the macrolide antibiotic azithromycin has been shown to exert neuroprotection in mice due to its immunomodulatory properties. Here, we have demonstrated that acute administration of a single dose of azithromycin upon reperfusion produces a dose-dependent (ED = 1.40 mg/kg; 95% CI = 0.48-4.03) reduction of ischemic brain damage measured 22 h after transient (2 h) middle cerebral artery occlusion (MCAo) in adult male rats. Neuroprotection by azithromycin (150 mg/kg, i.p., upon reperfusion) was associated with a significant elevation of signal transducer and activator of transcription 3 (STAT3) phosphorylation in astrocytes and neurons of the peri-ischemic motor cortex as detected after 2 and 22 h of reperfusion. By contrast, in the core region of the striatum, drug administration resulted in a dramatic elevation of STAT3 phosphorylation only after 22 h of reperfusion, being the signal mainly ascribed to infiltrating leukocytes displaying an M2 phenotype. These early molecular events were associated with a long-lasting neuroprotection, since a single dose of azithromycin reduced brain infarct damage and neurological deficit measured up to 7 days of reperfusion. These data, together with the evidence that azithromycin was effective in a clinically relevant time-window (i.e., when administered after 4.5 h of MCAo), provide robust preclinical evidence to support the importance of developing azithromycin as an effective acute therapy for ischemic stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2019.01256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902046PMC
November 2019

Anxiolytic-Like Effects of Bergamot Essential Oil Are Insensitive to Flumazenil in Rats.

Evid Based Complement Alternat Med 2019 14;2019:2156873. Epub 2019 Aug 14.

Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, 87036 Rende, Italy.

Anxiety disorders are one of the most common mental disorders, and benzodiazepines (BDZs), acting on gamma-aminobutyric acid type A (GABA-A) receptor complex, represent the most common antianxiety medications in the world. However, chronic BDZ use elicits several adverse reactions. Reportedly, aromatherapy is safer for the management of anxiety. Bergamot essential oil (BEO) extracted from Risso Poiteau fruit, like other essential oils, is widely used in aromatherapy to relieve symptoms of stress-induced anxiety. Interestingly, preclinical data indicate that BEO induces anxiolytic-like/relaxant effects in animal behavioural tasks not superimposable to those of benzodiazepine diazepam. To better elucidate the involvement of GABAergic transmission, the present study examines the effects of pretreatment with flumazenil (FLZ), a benzodiazepine site antagonist, on BEO effects using open-field task (OFT) in rats. The data yielded show that FLZ does not significantly affect behavioural effects of the phytocomplex. These results demonstrate the lack of overlapping between BEO and BDZ behavioural effects, contributing to the characterization of the neurobiological profile of the essential oil for its rational use in aromatherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/2156873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710760PMC
August 2019

Neuropharmacology of the Neuropsychiatric Symptoms of Dementia and Role of Pain: Essential Oil of Bergamot as a Novel Therapeutic Approach.

Int J Mol Sci 2019 Jul 6;20(13). Epub 2019 Jul 6.

Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.

Aging of the population makes of dementia a challenge for health systems worldwide. The cognitive disturbance is a serious but not the only issue in dementia; behavioral and psychological syndromes known as neuropsychiatric symptoms of dementia remarkably reduce the quality of life. The cluster of symptoms includes anxiety, depression, wandering, delusions, hallucinations, misidentifications, agitation and aggression. The pathophysiology of these symptoms implicates all the neurotransmitter systems, with a pivotal role for the glutamatergic neurotransmission. Imbalanced glutamatergic and GABAergic neurotransmissions, over-activation of the extrasynaptic N-methyl-D-aspartate (NMDA) receptors and alterations of the latter have been linked to the development of neuropsychiatric symptoms experienced by almost the entire demented population. Drugs with efficacy and safety for prevention or long term treatment of these disorders are not available yet. Aromatherapy provides the best evidence for positive outcomes in the control of agitation, the most resistant symptom. Demented patients often cannot verbalize pain, resulting in unrelieved symptoms and contributing to agitation. Bergamot essential oil provides extensive preclinical evidence of analgesic properties. Incidentally, the essential oil of bergamot induces anxyolitic-like effects devoid of sedation, typical of benzodiazepines, with a noteworthy advantage for demented patients. These data, together with the reported safety profile, form the rational basis for bergamot as a neurotherapeutic to be trialed for the control of behavioral and psychological symptoms of dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20133327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651821PMC
July 2019

New Trends in Migraine Pharmacology: Targeting Calcitonin Gene-Related Peptide (CGRP) With Monoclonal Antibodies.

Front Pharmacol 2019 9;10:363. Epub 2019 Apr 9.

Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Migraine is a common neurologic disorder characterized by attacks consisting of unilateral, throbbing headache accompanied by photophobia, phonophobia, and nausea which remarkably reduces the patients' quality of life. Not migraine-specific non-steroidal anti-inflammatory drugs (NSAIDs) are effective in patients affected by mild episodic migraine whilst in moderate or severe episodic migraine and in chronic migraineurs triptans and preventative therapies are needed. Since these treatments are endowed with serious side effects and have limited effectiveness new pharmacological approaches have been investigated. The demonstrated pivotal role of calcitonin gene-related peptide (CGRP) has fostered the development of CGRP antagonists, unfortunately endowed with liver toxicity, and monoclonal antibodies (mAbs) toward circulating CGRP released during migraine attack or targeting its receptor. Currently, four mAbs, eptinezumab, fremanezumab, galcanezumab for CGRP and erenumab for CGRP canonical receptor, have been studied in clinical trials for episodic and chronic migraine. Apart from the proven effectiveness, these antibodies have resulted well tolerated and could improve the compliance of the patients due to their long half-lives allowing less frequent administrations. This study aims at investigating the still poorly clear pathogenesis of migraine and the potential role of anti-CGRP mAbs in the scenario of prophylaxis of migraine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2019.00363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465320PMC
April 2019

Diabetic retinopathy and age-related macular degeneration: a survey of pharmacoutilization and cost in Calabria, Italy.

Neural Regen Res 2019 Aug;14(8):1445-1448

Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

The aged population is constantly growing, thus fostering an increase in age-dependent diseases. Among these, diabetic retinopathy (DR) along with age-related macular degeneration entails progressive vision loss. Since such conditions are associated with the proliferation of novel vessels, their pharmacotherapeutic management consists of the intravitreal injection of anti-vascular endothelial growth factor drugs, able to hinder the driving of vascular proliferation prompted by vascular endothelial growth factor. The humanized anti-vascular endothelial growth factor monoclonal antibody ranibizumab provided evidence for efficacy in several trials, hence earning approval by the US Food and Drug Administration for therapeutic use in all the stages of DR. Due to the lack of epidemiologic and pharmacoeconomic evaluation in the local Calabria Region context, the present retrospective observational study focused on prevalence of DR and age-related macular degeneration, treatment and cost of therapy with ranibizumab in 870 patients arriving to clinical observation at the "Mater Domini" University Hospital in Calabria, Italy from January 2014 to June 2017. Data were extracted from the database of ophthalmology ward and subjected to statistical analysis. The results suggest that the most frequent retinal diseases are age-related macular degeneration and DR and that the use of ranibizumab has been decreasing over the 4-year study period together with the associated cost per patient which was similar for both disorders. Therefore, appropriateness of treatment with drugs other than ranibizumab needs to be assessed in this setting and deep monitoring of pharmacologic treatment for retinal diseases is necessary to prevent or delay visual acuity decrease and complete vision loss. Study procedures were performed in accordance with the "Mater Domini" University Hospital ethical standards of the responsible committee on human experimentation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1673-5374.253528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524505PMC
August 2019

The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux.

Sci Rep 2019 03 19;9(1):4881. Epub 2019 Mar 19.

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Antidepressants are commonly prescribed psychotropic substances for the symptomatic treatment of mood disorders. Their primary mechanism of action is the modulation of neurotransmission and the consequent accumulation of monoamines, such as serotonin and noradrenaline. However, antidepressants have additional molecular targets that, through multiple signaling cascades, may ultimately alter essential cellular processes. In this regard, it was previously demonstrated that clomipramine, a widely used FDA-approved tricyclic antidepressant, interferes with the autophagic flux and severely compromises the viability of tumorigenic cells upon cytotoxic stress. Consistent with this line of evidence, we report here that clomipramine undermines autophagosome formation and cargo degradation in primary dissociated neurons. A similar pattern was observed in the frontal cortex and liver of treated mice, as well as in the nematode Caenorhabditis elegans exposed to clomipramine. Together, our findings indicate that clomipramine may negatively regulate the autophagic flux in various tissues, with potential metabolic and functional implications for the homeostatic maintenance of differentiated cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-40887-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424961PMC
March 2019

Rapamycin and fasting sustain autophagy response activated by ischemia/reperfusion injury and promote retinal ganglion cell survival.

Cell Death Dis 2018 09 24;9(10):981. Epub 2018 Sep 24.

Ophtalmology Unit, Department of Experimental Medicine, University of Rome "Tor Vergata", 00133, Rome, Italy.

Autophagy, the cellular process responsible for degradation and recycling of cytoplasmic components through the autophagosomal-lysosomal pathway, is fundamental for neuronal homeostasis and its deregulation has been identified as a hallmark of neurodegeneration. Retinal hypoxic-ischemic events occur in several sight-treating disorders, such as central retinal artery occlusion, diabetic retinopathy, and glaucoma, leading to degeneration and loss of retinal ganglion cells. Here we analyzed the autophagic response in the retinas of mice subjected to ischemia induced by transient elevation of intraocular pressure, reporting a biphasic and reperfusion time-dependent modulation of the process. Ischemic insult triggered in the retina an acute induction of autophagy that lasted during the first hours of reperfusion. This early upregulation of the autophagic flux limited RGC death, as demonstrated by the increased neuronal loss observed in mice with genetic impairment of basal autophagy owing to heterozygous ablation of the autophagy-positive modulator Ambra1 (Ambra1). Upregulation of autophagy was exhausted 24 h after the ischemic event and reduced autophagosomal turnover was associated with build up of the autophagic substrate SQSTM-1/p62, decreased ATG12-ATG5 conjugate, ATG4 and BECN1/Beclin1 expression. Animal fasting or subchronic systemic treatment with rapamycin sustained and prolonged autophagy activation and improved RGC survival, providing proof of principle for autophagy induction as a potential therapeutic strategy in retinal neurodegenerative conditions associated with hypoxic/ischemic stresses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-018-1044-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155349PMC
September 2018

Evidence for accuracy of pain assessment and painkillers utilization in neuropsychiatric symptoms of dementia in Calabria region, Italy.

Neural Regen Res 2018 Sep;13(9):1619-1621

Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

During the clinical course of dementia, beside cognitive impairment and memory loss, a very complex challenge is posed by the neuropsychiatric symptoms (NPSs). Accurate evaluation and treatment of pain impacts positively the agitation of demented patients aged ≥ 65 years. To gather information on the utilization of pain killers in demented patients a preliminary survey has been conducted in collaboration with the Calabrian Pharmacovigilance Territorial Service of the health district of Catanzaro (Italy). The study has taken into consideration the prescriptions of acetylcholinesterase inhibitors and memantine during the period ranging from July 2015 to June 2016 and the percentage of patients treated against pain with non steroidal antinflammatory drugs, opioids, and anticonvulsants have been monitored. The latter have been evaluated statistically for difference between the treatment before (pre) and after (post) the settlement of acetylcholinesterase inhibitors (AChEI) or memantine therapy. The results do support accuracy in painkillers utilization in the course of dementia in the regional population of Calabria (Italy).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1673-5374.237125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126116PMC
September 2018
-->