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1.
Int J Neuropsychopharmacol ; 27(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38577951

RESUMEN

BACKGROUND: Anxiety disorders are highly prevalent and socio-economically costly. Novel pharmacological treatments for these disorders are needed because many patients do not respond to current agents or experience unwanted side effects. However, a barrier to treatment development is the variable and large placebo response rate seen in trials of novel anxiolytics. Despite this, the mechanisms that drive placebo responses in anxiety disorders have been little investigated, possibly due to low availability of convenient experimental paradigms. We aimed to develop and test a novel protocol for inducing placebo anxiolysis in the 7.5% CO2 inhalational model of generalized anxiety in healthy volunteers. METHODS: Following a baseline 20-minute CO2 challenge, 32 healthy volunteers were administered a placebo intranasal spray labelled as either the anxiolytic "lorazepam" or "saline." Following this, participants surreptitiously underwent a 20-minute inhalation of normal air. Post-conditioning, a second dose of the placebo was administered, after which participants completed another CO2 challenge. RESULTS: Participants administered sham "lorazepam" reported significant positive expectations of reduced anxiety (P = .001), but there was no group-level placebo effect on anxiety following CO2 challenge post-conditioning (Ps > .350). Surprisingly, we found many participants exhibited unexpected worsening of anxiety, despite positive expectations. CONCLUSIONS: Contrary to our hypothesis, our novel paradigm did not induce a placebo response, on average. It is possible that effects of 7.5% CO2 inhalation on prefrontal cortex function or behavior in line with a Bayesian predictive coding framework attenuated the effect of expectations on subsequent placebo response. Future studies are needed to explore these possibilities.


Asunto(s)
Ansiolíticos , Ansiedad , Dióxido de Carbono , Efecto Placebo , Humanos , Dióxido de Carbono/administración & dosificación , Dióxido de Carbono/farmacología , Masculino , Femenino , Adulto , Adulto Joven , Ansiolíticos/farmacología , Ansiolíticos/administración & dosificación , Administración por Inhalación , Ansiedad/tratamiento farmacológico , Ansiedad/inducido químicamente , Lorazepam/farmacología , Lorazepam/administración & dosificación , Método Doble Ciego
2.
CNS Spectr ; 28(1): 46-52, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-34736545

RESUMEN

BACKGROUND: Panic disorder (PD) is a prevalent and impairing anxiety disorder with previous reports suggesting that the longer the condition remains untreated, the greater the likelihood of nonresponse. However, patients with PD may wait for years before receiving a guideline-recommended pharmacological treatment. The widespread prescription of benzodiazepines (BDZ) for managing anxiety symptoms and disorders might delay the administration of pharmacotherapy according to guidelines (eg, selective serotonin reuptake inhibitors, SSRIs). The present study aimed to determine the mean duration of untreated illness (DUI) in a sample of PD patients, to quantify and compare DUI-SSRI to DUI-BDZ, and to compare findings with those from previous investigations. METHODS: Three hundred and fourteen patients with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition diagnosis of PD were recruited from an Italian outpatient psychotherapy unit, and epidemiological and clinical variables were retrieved from medical records. Descriptive statistical analyses were undertaken for sociodemographic and clinical variables, Wilcoxon matched-pair signed rank test was applied to compare the distribution of DUI-SSRI vs DUI-BDZ, and Welch's t test was performed to compare findings with those from previous studies. RESULTS: The mean DUI-SSRI of the total sample was 64.25 ± 112.74 months, while the mean DUI-BDZ was significantly shorter (35.09 ± 78.62 months; P < 0.0001). A significantly longer DUI-SSRI, compared to findings from previous studies, was also observed. CONCLUSIONS: The present results confirm a substantial delay in implementing adequate pharmacological treatments in patients with PD, and highlight the discrepancy between recommendations from international treatment guidelines and common clinical practice in relation to BDZ prescription.


Asunto(s)
Trastorno de Pánico , Humanos , Trastorno de Pánico/tratamiento farmacológico , Trastorno de Pánico/epidemiología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Benzodiazepinas/uso terapéutico , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/diagnóstico , Factores de Tiempo
3.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36674509

RESUMEN

Amyotrophic lateral sclerosis (ALS) is an incurable motor neuron disease whose etiology remains unresolved; nonetheless, mutations of superoxide dismutase 1 (SOD1) have been associated with several variants of ALS. Currently available pharmacologic interventions are only symptomatic and palliative in effect; therefore, there is a pressing demand for more effective drugs. This study examined potential therapeutic effects of growth hormone secretagogues (GHSs), a large family of synthetic compounds, as possible candidates for the treatment of ALS. Human neuroblastoma cells expressing the SOD1-G93A mutated protein (SH-SY5Y SOD1G93A cells) were incubated for 24 h with H2O2 (150 µM) in the absence, or presence, of GHS (1 µM), in order to study the protective effect of GHS against increased oxidative stress. The two GHSs examined in this study, hexarelin and JMV2894, protected cells from H2O2-induced cytotoxicity by activating molecules that regulate apoptosis and promote cell survival processes. These findings suggest the possibility of developing new GHS-based anti-oxidant and neuroprotective drugs with improved therapeutic potential. Further investigations are required for the following: (i) to clarify GHS molecular mechanisms of action, and (ii) to envisage the development of new GHSs that may be useful in ALS therapy.


Asunto(s)
Esclerosis Amiotrófica Lateral , Neuroblastoma , Humanos , Animales , Ratones , Superóxido Dismutasa-1/genética , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/genética , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Peróxido de Hidrógeno/farmacología , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/genética , Línea Celular , Modelos Animales de Enfermedad , Ratones Transgénicos
4.
CNS Spectr ; 27(1): 93-98, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-32883389

RESUMEN

BACKGROUND: Little is known about the post-acute effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The present study focused on the 6-month follow-up of a sample of patients with major depression, after the completion of an acute 4 weeks rTMS trial, with the aim of evaluating response (in terms of sustained and late response) and relapse rates. METHODS: Following the completion of an acute trial of rTMS (T0-T4), 31 drug-resistant depressed patients (bipolar or unipolar) entered a naturalistic follow-up period of 6 months, with three timepoints (T5, T6, and T7) during which they were assessed with the Hamilton Depression Rating Scale and the Young Mania Rating Scale. RESULTS: Results showed that in the 6 months following an acute transcranial magnetic stimulation (TMS) trial, a higher rate of late responders was observed among previously acute TMS nonresponders (63.64%, 7 out of 11) compared to the rate of relapse among those who had acutely responded to TMS (10%, 2 out of 20). In addition, an overall high rate of maintained response (90%) was observed. CONCLUSION: Present findings seem to support the possibility of obtaining a clinical response also after the end of an acute TMS trial in patients with major depression. The concomitant low rate of relapse observed at the end of follow-up along with a high rate of maintained response provides further support to the post-acute efficacy of TMS. Nonetheless, further controlled studies, with larger samples and longer follow-up observation, are needed to confirm the reported results.


Asunto(s)
Trastorno Depresivo Mayor , Estimulación Magnética Transcraneal , Depresión , Trastorno Depresivo Mayor/terapia , Estudios de Seguimiento , Humanos , Corteza Prefrontal , Recurrencia , Estimulación Magnética Transcraneal/métodos , Resultado del Tratamiento
5.
Neurol Sci ; 43(9): 5765-5767, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35842569

RESUMEN

BACKGROUND: Anti-CGRP monoclonal antibodies (CGRPmAbs) enlarged migraine prevention options. They work targetedly, safely, and efficiently in many patients. Inexplicably, a proportion of patients show scarce improvement. OBJECTIVE: To identify the possible role of personality traits, determined with the Personality Inventory for DSM5 (PID5), on the efficacy of CGRPmAbs on migraine. METHODS: We evaluated 3 parameters: monthly headache days (MHD), monthly painkillers intake (MPI), and MIDAS. For each parameter, patients were classified as: (A) non-responders (reduction < 3 0% vs. baseline); (B) partial responders (30-49% reduction); (C) full responders (reduction > 50%). RESULTS: Ninety-seven patients treated with CGRP-mAbs were included (33 galcanezumab, 13 fremanezumab, 51 erenumab). Considering attack reduction (MHD), 53 (54.6%) were full responders, 13 (13.4%) partial responders, and 31 (32%) non-responders. Considering MPI, 61 (62.9%) were full responders, 11 (11.3%) partial responders, and 24 (24.7%) non-responders. Concerning MIDAS, 53 (53%) were full responders, 17 (17.5%) partial responders, and 21 (21.6%) were non-responders. All the 97 patients were tested with the PID5. In terms of MHDs, non-responders, in comparison with responders, showed a significant excess of disinhibition, especially in relation with the anhedonia and depressivity facets. Concerning MPI, non-responders showed increased depressivity and distractibility. MIDAS non-responders had significantly higher scores in the antagonism domain and submissiveness facet. DISCUSSION: Non-responders seem to have different personality traits in comparison to responders, with a higher tendency toward depressed mood and difficulty to feel pleasure previously found in migraineurs vs. non-migraineurs: the more strict certain traits are, the more difficult to treat the migraine could be.


Asunto(s)
Antineoplásicos Inmunológicos , Trastornos Migrañosos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Péptido Relacionado con Gen de Calcitonina , Cefalea/tratamiento farmacológico , Humanos , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/prevención & control , Personalidad , Resultado del Tratamiento
6.
Int J Mol Sci ; 23(7)2022 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-35408847

RESUMEN

Combined AntiRetroviral Treatments (cARTs) used for HIV infection may result in varied metabolic complications, which in some cases, may be related to patient genetic factors, particularly microRNAs. The use of monozygotic twins, differing only for HIV infection, presents a unique and powerful model for the controlled analysis of potential alterations of miRNAs regulation consequent to cART treatment. Profiling of 2578 mature miRNA in the subcutaneous (SC) adipose tissue and plasma of monozygotic twins was investigated by the GeneChip® miRNA 4.1 array. Real-time PCR and ddPCR experiments were performed in order to validate differentially expressed miRNAs. Target genes of deregulated miRNAs were predicted by the miRDB database (prediction score > 70) and enrichment analysis was carried out with g:Profiler. Processes in SC adipose tissue most greatly affected by miRNA up-regulation included (i) macromolecular metabolic processes, (ii) regulation of neurogenesis, and (iii) protein phosphorylation. Furthermore, KEGG analysis revealed miRNA up-regulation involvement in (i) insulin signaling pathways, (ii) neurotrophin signaling pathways, and (iii) pancreatic cancer. By contrast, miRNA up-regulation in plasma was involved in (i) melanoma, (ii) p53 signaling pathways, and (iii) focal adhesion. Our findings suggest a mechanism that may increase the predisposition of HIV+ patients to insulin resistance and cancer.


Asunto(s)
Infecciones por VIH , MicroARNs , Biología Computacional , Perfilación de la Expresión Génica , Infecciones por VIH/genética , Humanos , MicroARNs/genética , Grasa Subcutánea , Gemelos Monocigóticos/genética
7.
Int J Clin Pract ; 75(12): e14890, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34538005

RESUMEN

PURPOSE: Emergency rooms (ERs) are usually the first point of contact with mental health services for adolescents with Substance Use Disorders (SUDs). However, only a minority of them receives proper treatment and follow-up indications, increasing the risk of relapses and poor prognosis. In this perspective, we sought to characterize and compare socio-demographic and clinical characteristics of adolescents with vs without SUDs accessing the ER, assessing potential differences in terms of discharge instructions. METHODS: A sample of 557 ER accesses of patients aged 15-25 years old in need of a psychiatric evaluation or with a psychiatric diagnosis at discharge was retrospectively analyzed. Patients were divided in two subgroups according to the presence of SUDs. RESULTS: About 32.1% of patients had SUDs when accessing the ER. Among these, 62% were unknown to any psychiatric services and 57% were at their psychiatric onset. Nevertheless, considering discharge instructions, patients with current substance use received less therapeutic indication or were less frequently referred to psychiatric facilities, than those without substance use (57.8% vs 42.2%, P = .002). CONCLUSIONS: Substance abuse is strongly linked to psychopathology and ER accesses in young patients. However, we observed a large rate of SUDs patients unknown by any specialized mental health service, who received poor therapeutic and follow-up instructions at discharge. Improving communication between ER operators and young patients with SUDs could longitudinally reduce the risk of addiction and related disability, morbidity and mortality.


Asunto(s)
Trastornos Mentales , Servicios de Salud Mental , Trastornos Relacionados con Sustancias , Adolescente , Adulto , Servicio de Urgencia en Hospital , Humanos , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Alta del Paciente , Estudios Retrospectivos , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/terapia , Adulto Joven
8.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33802689

RESUMEN

Palmitoylethanolamide (PEA) is an endogenous lipid produced on demand by neurons and glial cells that displays neuroprotective properties. It is well known that inflammation and neuronal damage are strictly related processes and that microglia play a pivotal role in their regulation. The aim of the present work was to assess whether PEA could exert its neuroprotective and anti-inflammatory effects through the modulation of microglia reactive phenotypes. In N9 microglial cells, the pre-incubation with PEA blunted the increase of M1 pro-inflammatory markers induced by lipopolysaccharide (LPS), concomitantly increasing those M2 anti-inflammatory markers. Images of microglial cells were processed to obtain a set of morphological parameters that highlighted the ability of PEA to inhibit the LPS-induced M1 polarization and suggested that PEA might induce the anti-inflammatory M2a phenotype. Functionally, PEA prevented Ca2+ transients in both N9 cells and primary microglia and antagonized the neuronal hyperexcitability induced by LPS, as revealed by multi-electrode array (MEA) measurements on primary cortical cultures of neurons, microglia, and astrocyte. Finally, the investigation of the molecular pathway indicated that PEA effects are not mediated by toll-like receptor 4 (TLR4); on the contrary, a partial involvement of cannabinoid type 2 receptor (CB2R) was shown by using a selective receptor inverse agonist.


Asunto(s)
Amidas/farmacología , Etanolaminas/farmacología , Microglía/metabolismo , Fármacos Neuroprotectores/farmacología , Ácidos Palmíticos/farmacología , Adenosina Trifosfato/farmacología , Animales , Calcio/metabolismo , Polaridad Celular/efectos de los fármacos , Células Cultivadas , Citocinas/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/farmacología , Ratones , Microglía/efectos de los fármacos , FN-kappa B/metabolismo , Ratas , Receptor Cannabinoide CB2/metabolismo , Células THP-1 , Acetato de Tetradecanoilforbol/farmacología , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
9.
Artículo en Inglés | MEDLINE | ID: mdl-34497661

RESUMEN

INTRODUCTION: Problematic Usage of the Internet (PUI) refers to a broad and likely heterogeneous group of Internet-related conditions associated with behavioural disturbances and functional impairment. METHODS: Within PUI several conditions have been reported, including Gaming Disorder, Shopping Addiction, Cyberchondria, Gambling Disorder, Cyberpornography Addiction and Cyberbullying. While increasing reports in the field try to define the epidemiologic and clinical boundaries of these conditions, the rapid and continuous evolution of Internet related behaviours as well as their problematic/pathological expressions are often difficult to diagnose, assess, approach with treatment interventions and follow-up. RESULTS: In addition, some of the PUI-related conditions show characteristics of addiction to the Internet as a preferential tool to engage in specific behaviours, while some others exclusively manifest on the Internet, making it necessary to find distinct assessment and treatment pathways. CONCLUSION: The inclusion of Internet Gaming Disorder in Section III by the DSM-5 and the recognition of Gaming Disorder by the ICD-11 opened the way for a systematic clinical investigation of this and other PUI-related conditions, particularly in terms of preventive and therapeutic strategies. The present article is aimed at offering an updated clinical overview on the main expressions of PUI, focussing on the latest acquisitions in this evolving field.

10.
Pulm Pharmacol Ther ; 62: 101916, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32205280

RESUMEN

TLQP-21, a peptide encoded by the prohormone VGF, is expressed in neuroendocrine cells and can modulate inflammatory processes. Since TLQP-21 can bind the complement 3a receptor 1 on macrophages, interest has risen in this peptide as a potential drug for the treatment of Acute Respiratory Distress Syndrome (ARDS), whose hospital mortality can reach 35-46%. Since no effective pharmacologic therapies are available, our aim was to exploit the potential of a short analog of TLQP-21(JMV5656) in order to modulate the inflammatory process in ARDS and the progression to pulmonary fibrosis in an experimental model of unilateral acid aspiration in mice. Mice were divided in 2 treatment groups. In the acute protocol, mice received intra-peritoneal injection of either vehicle or 0.6 mg/kg JMV5656 on experimental days 1 and 2, and ARDS was induced on day 3 under deep anesthesia by instillation of HCl (1.5 ml/kg of 0.1 M HCl in 0.9% NaCl) into the right lung; all measurements were performed 24 h later. In the subacute protocol, mice were treated as previously, but treatment with vehicle or JMV5656 was repeated also on day 4 and measurements were made 2 weeks later. Twenty-four hours after acid instillation, the total number of immune cell in the BAL rose sharply due primarily to an increase in the PMN population which increased from 1% up to 58% of total cell numbers. JMV5656 significantly reduced PMN recruitment into the alveolar space, but had no effects on cytokine levels in BAL. Two weeks after acid injury, static compliance of the right lung was significantly higher in the JMV5656-treated group compared to vehicle-treated group. Treatment with JMV5656 also blunted the acid-induced collagen deposition in the right lung. These results suggest that JMV5656 can ameliorate mechanical compliance, and reduce collagen deposition in acid-injured lungs in mice. This effect was likely due to the ability of JMV5656 to inhibit PMN recruitment in the injured lung.


Asunto(s)
Lesión Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/tratamiento farmacológico , Drogas Sintéticas/farmacología , Animales , Lavado Broncoalveolar , Citocinas , Pulmón/efectos de los fármacos , Lesión Pulmonar/inducido químicamente , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Fragmentos de Péptidos , Fibrosis Pulmonar/inducido químicamente , Síndrome de Dificultad Respiratoria
12.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-31491959

RESUMEN

Growth hormone secretagogues (GHS) are a family of synthetic molecules, first discovered in the late 1970s for their ability to stimulate growth hormone (GH) release. Many effects of GHS are mediated by binding to GHS-R1a, the receptor for the endogenous hormone ghrelin, a 28-amino acid peptide isolated from the stomach. Besides endocrine functions, both ghrelin and GHS are endowed with some relevant extraendocrine properties, including stimulation of food intake, anticonvulsant and anti-inflammatory effects, and protection of muscle tissue in different pathological conditions. In particular, ghrelin and GHS inhibit cardiomyocyte and endothelial cell apoptosis and improve cardiac left ventricular function during ischemia-reperfusion injury. Moreover, in a model of cisplatin-induced cachexia, GHS protect skeletal muscle from mitochondrial damage and improve lean mass recovery. Most of these effects are mediated by GHS ability to preserve intracellular Ca2+ homeostasis. In this review, we address the muscle-specific protective effects of GHS mediated by Ca2+ regulation, but also highlight recent findings of their therapeutic potential in pathological conditions characterized by skeletal or cardiac muscle impairment.


Asunto(s)
Señalización del Calcio/efectos de los fármacos , Hormona del Crecimiento/farmacología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Secretagogos/farmacología , Animales , Humanos
13.
Int J Mol Sci ; 21(1)2019 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-31878142

RESUMEN

VGF gene encodes for a neuropeptide precursor of 68 kDa composed by 615 (human) and 617 (rat, mice) residues, expressed prevalently in the central nervous system (CNS), but also in the peripheral nervous system (PNS) and in various endocrine cells. This precursor undergoes proteolytic cleavage, generating a family of peptides different in length and biological activity. Among them, TLQP-21, a peptide of 21 amino acids, has been widely investigated for its relevant endocrine and extraendocrine activities. The complement complement C3a receptor-1 (C3aR1) has been suggested as the TLQP-21 receptor and, in different cell lines, its activation by TLQP-21 induces an increase of intracellular Ca2+. This effect relies both on Ca2+ release from the endoplasmic reticulum (ER) and extracellular Ca2+ entry. The latter depends on stromal interaction molecules (STIM)-Orai1 interaction or transient receptor potential channel (TRPC) involvement. After Ca2+ entry, the activation of outward K+-Ca2+-dependent currents, mainly the KCa3.1 currents, provides a membrane polarizing influence which offset the depolarizing action of Ca2+ elevation and indirectly maintains the driving force for optimal Ca2+ increase in the cytosol. In this review, we address the main endocrine and extraendocrine actions displayed by TLQP-21, highlighting recent findings on its mechanism of action and its potential in different pathological conditions.


Asunto(s)
Señalización del Calcio/efectos de los fármacos , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Neuropéptidos/química , Fragmentos de Péptidos/química , Fragmentos de Péptidos/farmacología , Animales , Citosol/efectos de los fármacos , Citosol/metabolismo , Humanos , Moléculas de Interacción Estromal/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismo
14.
Environ Health ; 16(1): 130, 2017 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-29212512

RESUMEN

CORRECTION: After publication of the article [1], it has been brought to our attention that the thirteenth author of this article has had their name spelt incorrectly. In the original article the spelling "Laura Rizzir" was used. In fact the correct spelling should be "Laura Rizzi".

15.
Environ Health ; 14: 54, 2015 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-26092037

RESUMEN

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.


Asunto(s)
Conferencias de Consenso como Asunto , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/efectos adversos , Sustancias Peligrosas/efectos adversos , Congresos como Asunto , Diabetes Mellitus/inducido químicamente , Humanos , Italia , Síndrome Metabólico/inducido químicamente , Obesidad/inducido químicamente
16.
Biology (Basel) ; 13(1)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38275737

RESUMEN

Chemotherapy-induced peripheral neuropathy (CIPN) commonly arises as a side effect of diverse cancer chemotherapy treatments. This condition presents symptoms such as numbness, tingling, and altered sensation in patients, often accompanied by neuropathic pain. Pathologically, CIPN is characterized by an intensive "dying-back" axonopathy, starting at the intra-epidermal sensory innervations and advancing retrogradely. The lack of comprehensive understanding regarding its underlying mechanisms explains the absence of effective treatments for CIPN. Recent investigations into axon degeneration mechanisms have pinpointed nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) and sterile alpha and TIR motif-containing 1 protein (SARM1) as pivotal mediators of injury-induced axonal degeneration. In this review, we aim to explore various studies shedding light on the interplay between NMNAT2 and SARM1 proteins and their roles in the progression of CIPN.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38425116

RESUMEN

BACKGROUND: Compared to Immediate-Release (IR) metformin, Extended-Release (ER) metformin reduces side effects and pill burden while improving adherence; however, there is little real-life data on patient satisfaction with this innovative formulation to guide physicians toward a more holistic approach. OBJECTIVE: Our goal is to train general practitioners on holistic patient management, with the aim of increasing patient satisfaction and treatment adherence, reducing side effects, and improving quality of life in patients with poor tolerance to metformin-IR. DESIGN AND METHODS: We designed an educational program for physicians called SlowDiab, aimed at establishing a holistic patient approach. In this context, adult patients with T2DM who experienced gastrointestinal discomfort with metformin-IR were enrolled and switched to metformin- ER. Data on glycemic control were collected at baseline and 2 months after switching. A survey was carried out on patients to assess their level of satisfaction. RESULTS: In 69 enrolled patients (mean [min-max] age, 68.2 [41-90]), side effects decreased after switching from 61.8% to 16.2% (p < 0.01), and the mean perceived burden of adverse events on a scale of 1 to 10 also decreased (6.17 vs. 3.82; p < 0.05). Among patients previously intolerant to metformin-IR, 74.3% reported no longer experiencing any side effects after the switch. The mean number of tablets taken daily (2.28 vs. 1.66; p < 0.01) and mean plasma glycated hemoglobin (HbA1c) values (7.0% vs. 6.7%; p < 0.05) decreased, while 93.8% of patients were satisfied with the treatment change. Moreover, 84.2% reported an improvement in glycemic control after the switch. CONCLUSION: In a real-life setting, an educational program for general practitioners confirmed that metformin ER reduces side effects and improves pill burden, therapeutic adherence, and patient satisfaction compared to metformin IR.

18.
Clin Neuropsychiatry ; 20(3): 183-192, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37522109

RESUMEN

Objective: Depression represents one of the most severe psychiatric disorders, characterized by low mood episodes, as well as loss of interest. Major Depressive Episodes (MDE) treatment relies primarily on monoaminergic prescriptions. However, although the presence of many antidepressant medications, their efficacy is still partial. A promising intervention to improve antidepressant treatment may be the use of adjunctive nutraceuticals. Aim of the present study was to assess the efficacy of a N-Acetyl-cysteine, S-Adenosyl-L-Methionine and Folic acid's combination for the treatment of depressive symptoms in a sample of MDE patients. Method: Fifty outpatients with a MDE diagnosis in the context of different psychiatric disorders such as Major Depression, Bipolar Disorder, Anxiety disorders, and Personality disorders were recruited. The sample was divided into different groups based on the nutraceutical administration: a) concurrently with an AD (starter group); b) add-on to an already prescribed treatment; c) single treatment. Results: A significant reduction of CGI-Severity and Improvement scores from baseline to the end of treatment was found. Moreover, the starter group showed a significantly greater CGI-Improvement score compared to the other groups. Ninety-four percent of patients did not show any side effects. Conclusions: The present study showed promising results for the use of nutraceuticals in the add-on treatment of MDE. Those compounds may be considered a versatile, tolerable, and effective add-on treatment for the reduction of depressive symptoms impact and for improving the functioning of patients affected by MDE.

19.
Curr Neuropharmacol ; 21(12): 2376-2394, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36111771

RESUMEN

Amyotrophic lateral sclerosis (ALS) arises from neuronal death due to complex interactions of genetic, molecular, and environmental factors. Currently, only two drugs, riluzole and edaravone, have been approved to slow the progression of this disease. However, ghrelin and other ligands of the GHS-R1a receptor have demonstrated interesting neuroprotective activities that could be exploited in this pathology. Ghrelin, a 28-amino acid hormone, primarily synthesized and secreted by oxyntic cells in the stomach wall, binds to the pituitary GHS-R1a and stimulates GH secretion; in addition, ghrelin is endowed with multiple extra endocrine bioactivities. Native ghrelin requires esterification with octanoic acid for binding to the GHS-R1a receptor; however, this esterified form is very labile and represents less than 10% of circulating ghrelin. A large number of synthetic compounds, the growth hormone secretagogues (GHS) encompassing short peptides, peptoids, and non-peptidic moieties, are capable of mimicking several biological activities of ghrelin, including stimulation of GH release, appetite, and elevation of blood IGF-I levels. GHS have demonstrated neuroprotective and anticonvulsant effects in experimental models of pathologies both in vitro and in vivo. To illustrate, some GHS, currently under evaluation by regulatory agencies for the treatment of human cachexia, have a good safety profile and are safe for human use. Collectively, evidence suggests that ghrelin and cognate GHS may constitute potential therapies for ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral , Ghrelina , Humanos , Ghrelina/uso terapéutico , Ghrelina/metabolismo , Receptores de Ghrelina/fisiología , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Secretagogos , Hormona del Crecimiento/metabolismo
20.
Clin Neuropsychiatry ; 20(1): 61-66, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36936622

RESUMEN

Objective: health care workers (HCWs) represent a vulnerable group in the COVID-19 pandemic, given the exposure to greater risk and higher levels of work-related stress. Neurofeedback (NF) has shown to be effective in the treatment of stress-related symptoms. We aimed to assess the effectiveness of an alpha-increase NF protocol for the treatment of acute stress symptoms in HCWs exposed to the COVID-19 pandemic. Method: eighteen medical doctors on duty during the COVID-19 health emergency underwent an intensive NF alpha-increase protocol. The mean alpha wave values were recorded at the beginning (T0) and at the last day of stimulation (T1). Rapid Stress Assessment: Italian version; Copenhagen Burnout Inventory (CBI); Pittsburgh Sleep Quality Index (PSQI), and Brief-COPE were administered as psychometric assessment. Results: a significant increase in alpha wave values and a significant reduction of the PSQI scores from T0 to T1 were found. Conclusions: NF alpha-increase protocol showed promising results in terms of stress modulation, sleep quality improvement, and safety in a pilot sample of HCWs.

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