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1.
BMC Psychiatry ; 20(1): 380, 2020 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-32690046

RESUMEN

BACKGROUND: Cognitive performance has been studied in adults with obsessive-compulsive symptoms (OCS) and in adult relatives of patients with obsessive-compulsive disorder (OCD) Meanwhile, few studies have been conducted with children under the same conditions. This study compared the neurocognitive domains previously associated with dysfunction in OCD, especially visuoconstructive ability, visuospatial memory, executive functions, and intelligence, in children and adolescents at high risk (HR) for OCD (n = 18) and non-OCD controls (NOC) (n = 31). METHODS: For the HR group, we considered the first-degree relatives of patients with OCD that present OCS, but do not meet diagnostic criteria for OCD. Psychiatric diagnosis was assessed by experienced clinicians using the Structured Clinical Interview for DSM-IV and OCS severity was measured by the Yale-Brown Obsessive-Compulsive Scale. Neurocognitive assessment was performed with a comprehensive neuropsychological battery. Performance on the cognitive domains was compared between groups using Multivariate Analysis of Variance, whereas performance on the neuropsychological variables was compared between groups using independent t-tests in a cognitive subdomain analysis. RESULTS: The cognitive domain analysis revealed a trend towards significance for impairments in the motor and processing speed domain (p = 0.019; F = 3.12) in the HR group. Moreover, the cognitive subdomain analysis identified a statistically significant underperformance in spatial working memory in the HR group when compared to the NOC group (p = 0.005; t = - 2.94), and a trend towards significance for impairments in non-verbal memory and visuoconstructive tasks in the HR group. CONCLUSIONS: Our results suggest impairments in spatial working memory and motor and processing speed in a non-clinical sample of HR participants. Considering the preliminary nature of our findings, further studies investigating these neurocognitive domains as potential predictors of pediatric OCD are warranted.


Asunto(s)
Trastorno Obsesivo Compulsivo , Adolescente , Adulto , Niño , Cognición , Función Ejecutiva , Humanos , Memoria a Corto Plazo , Pruebas Neuropsicológicas , Trastorno Obsesivo Compulsivo/diagnóstico
2.
J Biol Chem ; 293(6): 1957-1975, 2018 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-29284679

RESUMEN

Alzheimer's disease (AD) is a disabling and highly prevalent neurodegenerative condition, for which there are no effective therapies. Soluble oligomers of the amyloid-ß peptide (AßOs) are thought to be proximal neurotoxins involved in early neuronal oxidative stress and synapse damage, ultimately leading to neurodegeneration and memory impairment in AD. The aim of the current study was to evaluate the neuroprotective potential of mesenchymal stem cells (MSCs) against the deleterious impact of AßOs on hippocampal neurons. To this end, we established transwell cocultures of rat hippocampal neurons and MSCs. We show that MSCs and MSC-derived extracellular vesicles protect neurons against AßO-induced oxidative stress and synapse damage, revealed by loss of pre- and postsynaptic markers. Protection by MSCs entails three complementary mechanisms: 1) internalization and degradation of AßOs; 2) release of extracellular vesicles containing active catalase; and 3) selective secretion of interleukin-6, interleukin-10, and vascular endothelial growth factor to the medium. Results support the notion that MSCs may represent a promising alternative for cell-based therapies in AD.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Vesículas Extracelulares/metabolismo , Hipocampo/citología , Células Madre Mesenquimatosas/citología , Neuronas/metabolismo , Estrés Oxidativo , Sinapsis/metabolismo , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/química , Animales , Células Cultivadas , Técnicas de Cocultivo , Vesículas Extracelulares/genética , Hipocampo/metabolismo , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Células Madre Mesenquimatosas/metabolismo , Neuronas/citología , Ratas , Ratas Wistar , Factor A de Crecimiento Endotelial Vascular/metabolismo
4.
J Neurosci ; 33(23): 9626-34, 2013 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-23739959

RESUMEN

Brain accumulation of soluble amyloid-ß oligomers (AßOs) has been implicated in synapse failure and cognitive impairment in Alzheimer's disease (AD). However, whether and how oligomers of different sizes induce synapse dysfunction is a matter of controversy. Here, we report that low-molecular-weight (LMW) and high-molecular-weight (HMW) Aß oligomers differentially impact synapses and memory. A single intracerebroventricular injection of LMW AßOs (10 pmol) induced rapid and persistent cognitive impairment in mice. On the other hand, memory deficit induced by HMW AßOs (10 pmol) was found to be reversible. While memory impairment in LMW oligomer-injected mice was associated with decreased hippocampal synaptophysin and GluN2B immunoreactivities, synaptic pathology was not detected in the hippocampi of HMW oligomer-injected mice. On the other hand, HMW oligomers, but not LMW oligomers, induced oxidative stress in hippocampal neurons. Memantine rescued both neuronal oxidative stress and the transient memory impairment caused by HMW oligomers, but did not prevent the persistent cognitive deficit induced by LMW oligomers. Results establish that different Aß oligomer assemblies act in an orchestrated manner, inducing different pathologies and leading to synapse dysfunction. Furthermore, results suggest a mechanistic explanation for the limited efficacy of memantine in preventing memory loss in AD.


Asunto(s)
Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/toxicidad , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/tratamiento farmacológico , Memantina/farmacología , Fragmentos de Péptidos/farmacología , Péptidos beta-Amiloides/antagonistas & inhibidores , Animales , Células Cultivadas , Trastornos del Conocimiento/metabolismo , Masculino , Ratones , Peso Molecular , Fragmentos de Péptidos/antagonistas & inhibidores , Fragmentos de Péptidos/química , Fragmentos de Péptidos/toxicidad , Ratas
5.
Dalton Trans ; 53(12): 5466-5477, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38414337

RESUMEN

The significant attention drawn to IrIII-complexes in recent years has boosted the development of new compounds with advantageous photophysical features. However, obtaining IrIII deep-red-emitting complexes with long lived excited state, high colour purity and high quantum yield (Φ) remains a challenging task. To address this issue, this study reports the synthesis and photophysical investigation of three novel zwitterionic complexes, [Ir(C^N)2bqdc] (C^N = ppy, phq, and bzq), with ppy = 2-phenylpyridine (Ir-pb), phq = 2-phenylquinoline (Ir-qb), bzq = benzo[h]quinoline (Ir-bb), and bqdc = potassium 2,2'-biquinoline-4,4'-dicarboxylate. These complexes exhibit high quantum yields and long emission lifetimes with high colour purity in the deep-red region. The structural characterisation carried out by usual spectroscopic measurements supports the proposed structures, while the photophysical study unveiled the high contribution of the 3MLCT state to the hybrid emitter state, as endorsed by theoretical investigations. The desired correspondence between the calculations and the experimental data set affirmed the accuracy of the theoretical analysis, which enabled us to establish a relationship between the ground-to-excited-state geometry distortion and the lifetime through the nonradiative decay (knr). Furthermore, these newly synthesized complexes exhibit quenching in the presence of molecular oxygen. In deoxygenated DMSO solution the knr values halve, increasing the quantum yields (34.0, 10.6, and 26.6%) and the lifetimes (1.13, 1.11, and 1.72 µs), while leading to quite pure deep-red emission - CIE coordinates: (0.67, 0.33), (0.60, 0.40;), (0.65, 0.35) for Ir-pb, Ir-qb, and Ir-bb, respectively. These complexes display considerable potential for a wide range of applications, such as photodynamic therapy, due to their attractive photophysical properties, and are among the deep-red-emitting complexes reported in the literature with longer lifetimes and higher Φ.

6.
Psychiatry Res ; 331: 115627, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38113811

RESUMEN

Genetic and non-genetic factors contribute to obsessive-compulsive disorder (OCD), with strong evidence of familial clustering. Genomic studies in psychiatry have used the concepts of families that are "simplex" (one affected) versus "multiplex" (multiple affected). Our study compares demographic and clinical data from OCD probands in simplex and multiplex families to uncover potential differences. We analyzed 994 OCD probands (501 multiplex, 493 simplex) from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC). Clinicians administered the Structured Clinical Interview for DSM-IV (SCID-IV) to diagnose, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) to assess severity, and Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) to assess symptom dimensionality. Demographics, clinical history, and family data were collected. Compared to simplex probands, multiplex probands had earlier onset, higher sexual/religious and hoarding dimensions severity, increased comorbidity with other obsessive-compulsive-related disorders (OCRD), and higher family history of psychiatric disorders. These comparisons provide the first insights into demographic and clinical differences between Latin American simplex and multiplex families with OCD. Distinct clinical patterns may suggest diverse genetic and environmental influences. Further research is needed to clarify these differences, which have implications for symptom monitoring and management.


Asunto(s)
Trastorno Obsesivo Compulsivo , Humanos , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/genética , Trastorno Obsesivo Compulsivo/diagnóstico , Comorbilidad , Trastorno de Personalidad Compulsiva , Brasil/epidemiología , Conducta Sexual
7.
J Biol Chem ; 287(10): 7436-45, 2012 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-22235132

RESUMEN

Cognitive decline in Alzheimer disease (AD) is increasingly attributed to the neuronal impact of soluble oligomers of the amyloid-ß peptide (AßOs). Current knowledge on the molecular and cellular mechanisms underlying the toxicity of AßOs stems largely from rodent-derived cell/tissue culture experiments or from transgenic models of AD, which do not necessarily recapitulate the complexity of the human disease. Here, we used DNA microarray and RT-PCR to investigate changes in transcription in adult human cortical slices exposed to sublethal doses of AßOs. The results revealed a set of 27 genes that showed consistent differential expression upon exposure of slices from three different donors to AßOs. Functional classification of differentially expressed genes revealed that AßOs impact pathways important for neuronal physiology and known to be dysregulated in AD, including vesicle trafficking, cell adhesion, actin cytoskeleton dynamics, and insulin signaling. Most genes (70%) were down-regulated by AßO treatment, suggesting a predominantly inhibitory effect on the corresponding pathways. Significantly, AßOs induced down-regulation of synaptophysin, a presynaptic vesicle membrane protein, suggesting a mechanism by which oligomers cause synapse failure. The results provide insight into early mechanisms of pathogenesis of AD and suggest that the neuronal pathways affected by AßOs may be targets for the development of novel diagnostic or therapeutic approaches.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Regulación de la Expresión Génica , Proteínas del Tejido Nervioso/biosíntesis , Adulto , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/terapia , Encéfalo/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos
8.
Braz J Psychiatry ; 44(2): 187-200, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35617698

RESUMEN

Obsessive-compulsive disorder (OCD) is a common psychiatric condition classically characterized by obsessions (recurrent, intrusive and unwanted thoughts) and compulsions (excessive, repetitive and ritualistic behaviors or mental acts). OCD is heterogeneous in its clinical presentation and not all patients respond to first-line treatments. Several neurocircuit models of OCD have been proposed with the aim of providing a better understanding of the neural and cognitive mechanisms involved in the disorder. These models use advances in neuroscience and findings from neuropsychological and neuroimaging studies to suggest links between clinical profiles that reflect the symptoms and experiences of patients and dysfunctions in specific neurocircuits. Several models propose that treatments for OCD could be improved if directed to specific neurocircuit dysfunctions, thereby restoring efficient neurocognitive function and ameliorating the symptomatology of each associated clinical profile. Yet, there are several important limitations to neurocircuit models of OCD. The purpose of the current review is to highlight some of these limitations, including issues related to the complexity of brain and cognitive function, the clinical presentation and course of OCD, etiological factors, and treatment methods proposed by the models. We also provide suggestions for future research to advance neurocircuit models of OCD and facilitate translation to clinical application.


Asunto(s)
Trastorno Obsesivo Compulsivo , Cognición , Conducta Compulsiva , Humanos , Neuroimagen , Conducta Obsesiva , Trastorno Obsesivo Compulsivo/diagnóstico
9.
Biomolecules ; 12(12)2022 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-36551331

RESUMEN

Leishmaniasis is a highly prevalent, yet neglected disease caused by protozoan parasites of the genus Leishmania. In the search for newer, safer, and more effective antileishmanial compounds, we herein present a study of the mode of action in addition to a detailed structural and biological characterization of LQOF-G6 [N-benzoyl-N'-benzyl-N″-(4-tertbutylphenyl)guanidine]. X-ray crystallography and extensive NMR experiments revealed that LQOF-G6 nearly exclusively adopts the Z conformation stabilized by an intramolecular hydrogen bond. The investigated guanidine showed selective inhibitory activity on Leishmania major cysteine protease LmCPB2.8ΔCTE (CPB) with ~73% inhibition and an IC50-CPB of 6.0 µM. This compound did not show any activity against the mammalian homologues cathepsin L and B. LQOF-G6 has been found to be nontoxic toward both organs and several cell lines, and no signs of hepatotoxicity or nephrotoxicity were observed from the analysis of biochemical clinical plasma markers in the treated mice. Docking simulations and experimental NMR measurements showed a clear contribution of the conformational parameters to the strength of the binding in the active site of the enzyme, and thus fit the differences in the inhibition values of LQOF-G6 compared to the other guanidines. Furthermore, the resulting data render LQOF-G6 suitable for further development as an antileishmanial drug.


Asunto(s)
Proteasas de Cisteína , Leishmania major , Leishmaniasis , Animales , Ratones , Proteasas de Cisteína/metabolismo , Guanidina , Virulencia , Leishmaniasis/tratamiento farmacológico , Mamíferos/metabolismo
10.
Rev Assoc Med Bras (1992) ; 67(5): 731-735, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34550264

RESUMEN

OBJECTIVE: The aim was to determine the epidemiological profile of dengue fever in Brazil between the years 2014 and 2019. METHODS: This is an observational, descriptive, cross-sectional, and retrospective study, which was carried out through the analysis of secondary data collected from the National System of Notification Appeals (SINAN) and from SUS Computer Department (DATASUS). RESULTS: The total number of reported cases was 5,867,255, and 2015 was the year with the highest cases (1,696,340). The cases were predominant in the Southeast and Midwest macro-regions, the female sex (55.6%), brown people (48%), and clinical and epidemiological criteria of confirmation (63.8%). Regarding the age group, it was observed that during the study period, the highest prevalence occurred in individuals between 20 and 39 years (38.3%). There was a change of serotype from DENV-1 to DENV-2, and dengue was the most prevalent classification (95.2%). Concerning hospitalization rates, there was a limited necessity of admissions (5.7%), as well as few deaths due to the notified disease (3,444). CONCLUSIONS: There was a significant growth in the number of dengue fever cases in Brazil in 2019, which represents a public health problem.


Asunto(s)
Dengue , Adulto , Brasil/epidemiología , Estudios Transversales , Dengue/epidemiología , Femenino , Humanos , Estudios Retrospectivos , Serogrupo , Adulto Joven
11.
Rev Assoc Med Bras (1992) ; 66(5): 607-614, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32638951

RESUMEN

BACKGROUND To determine the epidemiological profile of measles in Brasil from 2013 to 2018, and to evaluate the possible association between increased number of cases and vaccination coverage. METHODS This is an observational, descriptive, cross-sectional, retrospective study with quantitative approach, carried out through analysis of secondary data collected through the Notifiable Diseases Information System (SINAN), in the National Immunization Program (PNI). RESULTS The total number of reported cases was 10,886, with the year 2018 having the highest number (10,185). In the North macro-region (93.4%), male (55.53%), autochthonous cases from the city of residence (94.42%) and laboratory confirmation (99.09%) predominated. Regarding the age group, it was observed that in the period from 2013 to 2015 the highest prevalence occurred in <1 year, with 44.5%, 40.6% and 29.0%, respectively, while in 2018, the highest rate was in the 20-29 age group with 24.2%. Vaccination coverage was below 95%, except for SCR - D1 (first dose of triple viral) in the years 2013 to 2016. Regarding the outcome, there was a limited number of deaths secondary to measles (0.12%). CONCLUSIONS There was an exponential growth in the number of measles cases in Brasil in 2018, which represents a public health problem. In view of this, it is necessary to implement measures such as broad vaccination coverage and sanitary control at the borders, in order to reduce the incidence of this disease and, consequently, the number of deaths.


Asunto(s)
Sarampión/epidemiología , Brasil/epidemiología , Estudios Transversales , Brotes de Enfermedades , Humanos , Incidencia , Lactante , Masculino , Estudios Retrospectivos , Vacunación
12.
Fac Rev ; 9: 30, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33659962

RESUMEN

This article reviews recent advances in the genetics of obsessive-compulsive disorder (OCD). We cover work on the following: genome-wide association studies, whole-exome sequencing studies, copy number variation studies, gene expression, polygenic risk scores, gene-environment interaction, experimental animal systems, human cell models, imaging genetics, pharmacogenetics, and studies of endophenotypes. Findings from this work underscore the notion that the genetic architecture of OCD is highly complex and shared with other neuropsychiatric disorders. Also, the latest evidence points to the participation of gene networks involved in synaptic transmission, neurodevelopment, and the immune and inflammatory systems in this disorder. We conclude by highlighting that further study of the genetic architecture of OCD, a great part of which remains to be elucidated, could benefit the development of diagnostic and therapeutic approaches based on the biological basis of the disorder. Studies to date revealed that OCD is not a simple homogeneous entity, but rather that the underlying biological pathways are variable and heterogenous. We can expect that translation from bench to bedside, through continuous effort and collaborative work, will ultimately transform our understanding of what causes OCD and thus how best to treat it.

13.
Rev Assoc Med Bras (1992) ; 65(9): 1223-1228, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31618342

RESUMEN

OBJECTIVE: The objective of this article was to conduct a systematic review of the treatment of moderate-to-severe asthma by administrating Dupilumab. METHODS: A search on the online databases EBSCO, Scielo, PubMed, Medline Bireme, Lilacs, and The New England Journal of Medicine was conducted, publications from 2010 to 2018 were selected. The inclusion criteria were articles which contained control groups, tested the validity of Dupilumab, and verified the response of patients through controlled tests. For the search of such articles, the following keywords were used: "Dupilumab", "asthma", "Bronchial Asthma" AND "Asthma, Bronchial" AND their correspondent in Portuguese "asma", "Asma brônquica" and "Asma brônquica". The exclusion criteria were literature reviews, news, articles without control groups, articles on different subjects, Dupilumab studies on other diseases, articles concerning asthma without the use of Dupilumab, and repeated articles on the databases were discarded. RESULTS: The literature considers that the medication shows a good response for the treatment of moderate-to-severe asthma and assists in the improvement of lung function, aside from resulting in few side effects. It presents good efficacy, safety, and tolerance by patients. CONCLUSIONS: Dupilumab is promising for the treatment of asthma, whereas conventional therapy is deemed to be insufficient. More additional studies are needed to confirm the long-term safety and effectiveness.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Asma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Ensayos Clínicos Controlados como Asunto , Volumen Espiratorio Forzado , Humanos , Resultado del Tratamiento
14.
Stem Cell Res Ther ; 10(1): 332, 2019 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-31747944

RESUMEN

BACKGROUND: Mesenchymal stem cells (MSCs) have been explored as promising tools for treatment of several neurological and neurodegenerative diseases. MSCs release abundant extracellular vesicles (EVs) containing a variety of biomolecules, including mRNAs, miRNAs, and proteins. We hypothesized that EVs derived from human Wharton's jelly would act as mediators of the communication between hMSCs and neurons and could protect hippocampal neurons from damage induced by Alzheimer's disease-linked amyloid beta oligomers (AßOs). METHODS: We isolated and characterized EVs released by human Wharton's jelly mesenchymal stem cells (hMSC-EVs). The neuroprotective action of hMSC-EVs was investigated in primary hippocampal cultures exposed to AßOs. RESULTS: hMSC-EVs were internalized by hippocampal cells in culture, and this was enhanced in the presence of AßOs in the medium. hMSC-EVs protected hippocampal neurons from oxidative stress and synapse damage induced by AßOs. Neuroprotection by hMSC-EVs was mediated by catalase and was abolished in the presence of the catalase inhibitor, aminotriazole. CONCLUSIONS: hMSC-EVs protected hippocampal neurons from damage induced by AßOs, and this was related to the transfer of enzymatically active catalase contained in EVs. Results suggest that hMSC-EVs should be further explored as a cell-free therapeutic approach to prevent neuronal damage in Alzheimer's disease.


Asunto(s)
Péptidos beta-Amiloides/toxicidad , Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/citología , Neuronas/patología , Neuroprotección , Estrés Oxidativo , Sinapsis/patología , Gelatina de Wharton/citología , Animales , Biomarcadores/metabolismo , Catalasa/metabolismo , Exosomas/metabolismo , Exosomas/ultraestructura , Vesículas Extracelulares/efectos de los fármacos , Vesículas Extracelulares/ultraestructura , Hipocampo/patología , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuroprotección/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Multimerización de Proteína , Ratas , Especies Reactivas de Oxígeno/metabolismo , Sinapsis/efectos de los fármacos
15.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 44(2): 187-200, Apr. 2022. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1374588

RESUMEN

Obsessive-compulsive disorder (OCD) is a common psychiatric condition classically characterized by obsessions (recurrent, intrusive and unwanted thoughts) and compulsions (excessive, repetitive and ritualistic behaviors or mental acts). OCD is heterogeneous in its clinical presentation and not all patients respond to first-line treatments. Several neurocircuit models of OCD have been proposed with the aim of providing a better understanding of the neural and cognitive mechanisms involved in the disorder. These models use advances in neuroscience and findings from neuropsychological and neuroimaging studies to suggest links between clinical profiles that reflect the symptoms and experiences of patients and dysfunctions in specific neurocircuits. Several models propose that treatments for OCD could be improved if directed to specific neurocircuit dysfunctions, thereby restoring efficient neurocognitive function and ameliorating the symptomatology of each associated clinical profile. Yet, there are several important limitations to neurocircuit models of OCD. The purpose of the current review is to highlight some of these limitations, including issues related to the complexity of brain and cognitive function, the clinical presentation and course of OCD, etiological factors, and treatment methods proposed by the models. We also provide suggestions for future research to advance neurocircuit models of OCD and facilitate translation to clinical application.

16.
FASEB J ; 18(12): 1366-72, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15333579

RESUMEN

In the past two decades, a large body of evidence has established a causative role for the beta-amyloid peptide (Abeta) in Alzheimer's disease (AD). However, recent debate has focused on whether amyloid fibrils or soluble oligomers of Abeta are the main neurotoxic species that contribute to neurodegeneration and dementia. Considerable early evidence has indicated that amyloid fibrils are toxic, but some recent studies support the notion that Abeta oligomers are the primary neurotoxins. While this crucial aspect of AD pathogenesis remains controversial, effective therapeutic strategies should ideally target both oligomeric and fibrillar species of Abeta. Here, we describe the anti-amyloidogenic and neuroprotective actions of some di- and tri-substituted aromatic compounds. Inhibition of the formation of soluble Abeta oligomers was monitored using a specific antibody-based assay that discriminates between Abeta oligomers and monomers. Thioflavin T and electron microscopy were used to screen for inhibitors of fibril formation. Taken together, these results led to the identification of compounds that more effectively block Abeta oligomerization than fibrillization. It is significant that such compounds completely blocked the neurotoxicity of Abeta to rat hippocampal neurons in culture. These findings provide a basis for the development of novel small molecule Abeta inhibitors with potential applications in AD.


Asunto(s)
Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/química , Fármacos Neuroprotectores/farmacología , Placa Amiloide/química , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Animales , Benzotiazoles , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Hipocampo/citología , Concentración 50 Inhibidora , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Placa Amiloide/metabolismo , Estructura Cuaternaria de Proteína/efectos de los fármacos , Ratas , Solubilidad , Tiazoles
17.
Saude e pesqui. (Impr.) ; 13(4): 779-787, set-dez 2020.
Artículo en Portugués | LILACS-Express | LILACS | ID: biblio-1150561

RESUMEN

O climatério é uma fase da vida da mulher que se caracteriza pelo final da vida reprodutiva e o início da senescência. O objetivo deste estudo foi avaliar como as alterações físicas e fisiológicas da menopausa influenciam a qualidade de vida das mulheres, para tanto, foi utilizado o questionário Menopause Rating Scale. A amostra foi composta por 100 mulheres, com média de idade de 67,2 (±8,3) anos. O início da menopausa foi aos 48,06 anos (±8,06). No Menopause Rating Scale, houve presença de sintomatologia em 91% das participantes, a intensi-dade frequente foi a moderada, em cada um dos domínios, os sintomas dominantes foram as queixas locomotoras, o esgotamento físico e mental e a secura vaginal. Na correlação entre as queixas e comorbidades, o resultado foi significativo (p=0.05). Conclui-se que os sintomas apre-sentados na pós-menopausa não influenciam diretamente a qualidade de vida dessas mulheres.


The climacteric is a phase in a woman's life marked by the end of reproductive life and the beginning of senescence. Current study evaluated how physical and physiological changes in menopause influence the quality of life of postmenopausal females. Menopause Rating Scale questionnaire was used to assess quality of life. The sample consisted of 100 females, mean age 67.2±8.3 years old. The onset of menopause was at 48.06±8.06 years old. In the Menopause Rating Scale, symptomatology was present in 91% of participants; the intensity was moderate in each domain; the dominant symptoms were physical and mental exhaustion and vaginal dryness. In the correlation between complaints and comorbidities, the result was significant (p = 0.05). Results show symptoms present in the post-menopause do not directly influence the quality of life of these women.

18.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 66(5): 607-614, 2020. tab, graf
Artículo en Inglés | SES-SP, LILACS | ID: biblio-1136247

RESUMEN

SUMMARY BACKGROUND To determine the epidemiological profile of measles in Brasil from 2013 to 2018, and to evaluate the possible association between increased number of cases and vaccination coverage. METHODS This is an observational, descriptive, cross-sectional, retrospective study with quantitative approach, carried out through analysis of secondary data collected through the Notifiable Diseases Information System (SINAN), in the National Immunization Program (PNI). RESULTS The total number of reported cases was 10,886, with the year 2018 having the highest number (10,185). In the North macro-region (93.4%), male (55.53%), autochthonous cases from the city of residence (94.42%) and laboratory confirmation (99.09%) predominated. Regarding the age group, it was observed that in the period from 2013 to 2015 the highest prevalence occurred in <1 year, with 44.5%, 40.6% and 29.0%, respectively, while in 2018, the highest rate was in the 20-29 age group with 24.2%. Vaccination coverage was below 95%, except for SCR - D1 (first dose of triple viral) in the years 2013 to 2016. Regarding the outcome, there was a limited number of deaths secondary to measles (0.12%). CONCLUSIONS There was an exponential growth in the number of measles cases in Brasil in 2018, which represents a public health problem. In view of this, it is necessary to implement measures such as broad vaccination coverage and sanitary control at the borders, in order to reduce the incidence of this disease and, consequently, the number of deaths.


RESUMO OBJETIVO Determinar o perfil epidemiológico do sarampo no Brasil no período de 2013 a 2018, além da possível correlação entre incidência de casos e cobertura vacinal. MÉTODO Trata-se uma pesquisa observacional, com delineamento descritivo, transversal, retrospectivo e com abordagem quantitativa, feita por meio de análises de dados secundários coletados no Sistema Nacional de Agravos de Notificação (Sinan), no Programa Nacional de Imunizações (PNI). RESULTADOS O total de casos confirmados foi 10.886, sendo o ano de 2018 com o maior número (10.185). Predominou a macrorregião Norte (93,4%), sexo masculino (55,53%), casos autóctones do município de residência (94,42%) e confirmação laboratorial (99,09%). Com relação à faixa etária, observou-se que, no período de 2013 a 2015, a maior prevalência ocorreu em <1 ano, com 44,5%, 40,6% e 29,0%, respectivamente, enquanto que, em 2018, o maior índice foi na faixa de 20-29 anos, com 24,2%. A cobertura vacinal ficou abaixo de 95%, exceto a SCR - D1 (primeira dose da tríplice viral) nos anos de 2013 a 2016. Quanto ao desfecho, houve limitado número de óbitos secundários ao sarampo (0,12%). CONCLUSÃO Verifica-se um crescimento exponencial no número de casos de sarampo no Brasil em 2018, o que representa um problema de saúde pública. Diante disso, carece que medidas como ampla cobertura vacinal e controle sanitário, nas fronteiras, sejam implementadas, a fim de reduzir a incidência dessa enfermidade e, consequentemente, o número de óbitos.


Asunto(s)
Humanos , Masculino , Lactante , Sarampión/epidemiología , Brasil/epidemiología , Incidencia , Brotes de Enfermedades , Estudios Transversales , Estudios Retrospectivos , Vacunación
19.
Rev. odontol. UNESP (Online) ; 48: e20190107, 2019. tab
Artículo en Inglés | LILACS, BBO | ID: biblio-1099191

RESUMEN

Abstract Introduction One of the most common causes of orofacial pain is temporomandibular disorder (TMD). Objective The aim of this study was to compare the effectiveness of acupuncture, ozone therapy and laser therapy in the treatment of muscle TMD patients through a randomized controlled trial. Material and method Twelve professors and postgraduate students from the University of Passo Fundo, diagnosed with TMD, aged between 23 and 50 years old, of both sexes, were evaluated. Individuals were randomly divided into 3 groups: G1: laser therapy, G2: acupuncture, and G3: ozone therapy. TMD diagnostic questionnaires (RDC / TMD), Quality of Life Questionnaire (OHIP-14), Pain Scale (VAS) and maximum mouth opening were applied. Descriptive statistics and percentage were used for sample characterization, which were presented using absolute and relative frequency distributions. Qualitative variables were analyzed with Wilcoxon tests p≤0.05. Result There was no statistically significant difference between treatments. Regarding pain and maximum mouth opening, the groups showed no statistical difference when individually analyzed, but when compared in general, they did (p=0.002 and p=0.003). Conclusion It can be considered that all treatments were able to decrease pain and improve maximal opening capacity related to muscle TMD. It can also be concluded that the TMD-related quality of life, in relation to the pain variable, was generally effective when compared before and after the interventions.


Resumo Introdução Uma das causas mais comuns de dores orofaciais é a disfunção temporomandibular (DTM). Objetivo O objetivo deste estudo foi comparar a efetividade da acupuntura, ozonioterapia e laserterapia no tratamento de pacientes com DTM muscular, através de um ensaio clínico randomizado. Material e método Foram avaliados 12 professores e estudantes de pós-graduação da Universidade de Passo Fundo, diagnosticados com DTM, com faixa etária entre 23 e 50 anos, de ambos os sexos. Os indivíduos foram divididos aleatoriamente em 3 grupos: G1: laserterapia, G2: acupuntura, e G3: ozonioterapia. Foram aplicados questionários de diagnóstico de DTM (RDC/TMD), questionário de Qualidade de Vida (OHIP-14), Escala de dor (EVA) e mensuração de abertura bucal máxima. Para caracterização da amostra, utilizaram-se estatísticas descritivas e percentagem, que foram apresentadas empregando-se distribuições de frequências absolutas e relativas. As variáveis qualitativas foram analisadas com os testes de Wilcoxon p≤0,05. Resultado Não houve diferença estatisticamente significativa entre os tratamentos. Em relação a dor e a abertura bucal máxima, os grupos não apresentaram diferença estatística quando analisados individualmente, mas quando comparados de maneira geral, apresentaram diferenças estatísticas (p=0,002 e p=0,003). Conclusão Pode-se considerar que todos os tratamentos foram capazes de diminuir a dor e melhorar a capacidade de abertura bucal máxima relacionadas à DTM muscular. Pode-se concluir ainda que a qualidade de vida relacionada à DTM, em relação a variável dor, de uma maneira geral mostrou-se efetiva quando comparada antes e após as intervenções.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Ozono/uso terapéutico , Trastornos de la Articulación Temporomandibular/terapia , Terapia por Acupuntura , Resultado del Tratamiento , Terapia por Luz de Baja Intensidad , Calidad de Vida
20.
Rev. med. (Säo Paulo) ; 98(4): 273-278, jul.-ago. 2019.
Artículo en Inglés | LILACS | ID: biblio-1023537

RESUMEN

Obsessive-Compulsive disorder (OCD) is a common psychiatric condition that leads to significant impairment in everyday life. Advancements in neurobiological investigations contributed to a better understanding of pathophysiological mechanisms behind OCD, leading to the understanding that current models employed to conceptualize OCD are not adequate and might be a significant factor in precluding further advancements in how OCD is treated. In this paper, we will use OCD as a model to discuss the limitations of the current diagnostic systems in Psychiatry and to present the novel perspectives based on neurobiological findings that might lead to considerable advancements in treatments for OCD.


Asunto(s)
Neurobiología/tendencias , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/fisiopatología , Trastorno Obsesivo Compulsivo/terapia
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