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1.
Eur Rev Med Pharmacol Sci ; 28(2): 571-576, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38305601

RESUMO

OBJECTIVE: This study aims to compare the effects of vaginal estrogen and hyaluronic acid on vulvovaginal atrophy. PATIENTS AND METHODS: This randomized controlled study included a total of 300 patients, with 150 patients in each group (Group E and Group H). The VHI score was determined based on a pre-treatment evaluation conducted by a gynecologist. After one month of receiving vaginal estrogen in Group E and vaginal hyaluronic acid in Group H, the patients were re-evaluated by their physicians. RESULTS: A statistically significant difference was found between the pre- and post-treatment VHI scores in Group E and Group H (p = 0.000; p = 0.000). No statistical difference was found between Group E and Group H in terms of treatment efficacy (p = 0.712). The pre- and post-treatment complaints of dryness, itching, dyspareunia, burning, and dysuria were found to be statistically significant in Group E and Group H (p = 0.000; p = 0.000; p = 0.000; p = 0.000; p = 0.000 in Group E, respectively) (p = 0.000; p = 0.000; p = 0.000; p = 0.000; p = 0.000 in Group H, respectively). No statistical difference was observed regarding dyspareunia, dysuria, and burning complaints (p = 0.632; p = 0.106; p = 0.128, respectively). However, hyaluronic acid was found to be significantly more effective for itching complaints (p = 0.002), while estrogen was found to be significantly more effective for dryness complaints (p = 0.012). CONCLUSIONS: Hyaluronic acid and estrogen were equally effective in vaginal treatment. Hyaluronic acid may be preferred for patients in whom hormonal therapy is contraindicated or for those who prefer non-hormonal therapy.


Assuntos
Dispareunia , Ácido Hialurônico , Feminino , Humanos , Estradiol/uso terapêutico , Estradiol/farmacologia , Dispareunia/patologia , Disuria/induzido quimicamente , Disuria/patologia , Pós-Menopausa , Vagina/patologia , Estrogênios/uso terapêutico , Estrogênios/farmacologia , Resultado do Tratamento , Atrofia/tratamento farmacológico , Atrofia/patologia , Prurido/patologia
2.
CNS Neurosci Ther ; 30(2): e14578, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38334254

RESUMO

BACKGROUND AND OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS. METHODS: A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS. RESULTS: A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS-FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1-2, dentate gyrus, and fimbria atrophy were correlated with worse memory. CONCLUSIONS: The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis.


Assuntos
Esclerose Amiotrófica Lateral , Demência Frontotemporal , Doenças Neurodegenerativas , Humanos , Imagem de Tensor de Difusão/métodos , Doenças Neurodegenerativas/patologia , Imageamento por Ressonância Magnética , Hipocampo/patologia , Biomarcadores , Testes Neuropsicológicos , Atrofia/patologia
3.
Brain Behav ; 14(1): e3381, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38376028

RESUMO

BACKGROUND: Apolipoprotein E (ApoE) ε4 carriers have a higher risk of developing Alzheimer's disease (AD) and show brain atrophy and cognitive decline even before diagnosis. OBJECTIVE: To predict ApoE ε4 status using gray matter volume (GMV) obtained from magnetic resonance imaging images and demographic data with machine learning (ML) methods. METHODS: We recruited 74 participants (25 probable AD, 24 amnestic mild cognitive impairment, and 25 cognitively normal older people) with known ApoE genotype (22 ApoE ε4 carriers and 52 noncarriers) and scanned them with three-dimensional (3D) T1-weighted (T1W) and 3D double inversion recovery (DIR) sequences. We extracted GMV from regions of interest related to AD pathology and used them as features along with age and mini-mental state examination (MMSE) scores to train different ML models. We performed both receiver operating characteristic curve analysis and the prediction analysis of the ApoE ε4 carrier with different ML models. RESULTS: The best model of ML analyses was a cubic support vector machine (SVM3) that used age, the MMSE score, and DIR GMVs at the amygdala, hippocampus, and precuneus as features (AUC = .88). This model outperformed models using T1W GMV or demographic data alone. CONCLUSION: Our results suggest that brain atrophy with DIR GMV and cognitive decline with aging can be useful biomarkers for predicting ApoE ε4 status and identifying individuals at risk of AD progression.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Apolipoproteína E4/genética , Alelos , Apolipoproteínas E/genética , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Genótipo , Cognição , Imageamento por Ressonância Magnética/métodos , Atrofia/patologia
4.
Alzheimers Res Ther ; 16(1): 42, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378643

RESUMO

INTRODUCTION: Optical coherence tomography angiography (OCT-A) is a novel tool that allows the detection of retinal vascular changes. We investigated the association of macular vessel density (VD) in the superficial plexus assessed by OCT-A with measures of cerebrovascular pathology and atrophy quantified by brain magnetic resonance imaging (MRI) in non-demented individuals. METHODS: Clinical, demographical, OCT-A, and brain MRI data from non-demented research participants were included. We analyzed the association of regional macular VD with brain vascular burden using the Fazekas scale assessed in a logistic regression analysis, and the volume of white matter hyperintensities (WMH) assessed in a multiple linear regression analysis. We also explored the associations of macular VD with hippocampal volume, ventricle volume and Alzheimer disease cortical signature (ADCS) thickness assessed in multiple linear regression analyses. All analyses were adjusted for age, sex, syndromic diagnosis and cardiovascular variables. RESULTS: The study cohort comprised 188 participants: 89 with subjective cognitive decline and 99 with mild cognitive impairment. No significant association of regional macular VD with the Fazekas categories (all, p > 0.111) and WMH volume (all, p > 0.051) were detected. VD in the nasal quadrant was associated to hippocampal volume (p = 0.007), but no other associations of macular VD with brain atrophy measures were detected (all, p > 0.05). DISCUSSION: Retinal vascular measures were not a proxy of cerebrovascular damage in non-demented individuals, while VD in the nasal quadrant was associated with hippocampal atrophy independently of the amyloid status.


Assuntos
Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Angiofluoresceinografia/métodos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Atrofia/patologia , Tomografia de Coerência Óptica/métodos
5.
Sci Rep ; 14(1): 1085, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212347

RESUMO

The genitourinary symptom of menopause (GSM) affects up to 65% of women, resulting in symptoms such as vulvovaginal dryness, discomfort, and dysuria, which significantly impacts quality of life. The current assessment methods rely on subjective questionnaires that can be influenced by individual differences, as well as invasive measurements that are time-consuming and not easily accessible. In this study, we explore the potential of a non-invasive and objective assessment tool called diffuse reflectance spectroscopy and imaging (DRSI) to evaluate tissue chromophores, including water, lipid, oxyhemoglobin, and deoxyhemoglobin. These measurements provide information about moisture content, lipid levels, oxygen saturation, and blood fraction, which can serve as surrogate markers for genital estrogen levels. Our findings reveal distinct differences in these chromophores among pre, peri, and postmenopausal subjects. By using lipid and blood fraction tissue chromophores in a K-Nearest Neighbour classifier model, we achieved a prediction accuracy of 65% compared to vaginal maturation index (VMI) that is clinically used to assess estrogen-related hormonal changes. When age was included as the third feature, the accuracy increased to 78%. We believe that by refining the study protocol and configuring the fiber probe to examine tissue chromophores both in the superficial vulva skin for epidermal water content and the deeper layers, DRSI has the potential to provide objective diagnosis and aid in monitoring the treatment outcome of GSM.


Assuntos
Menopausa , Qualidade de Vida , Feminino , Humanos , Projetos Piloto , Vagina/patologia , Análise Espectral , Estrogênios , Água , Lipídeos , Atrofia/patologia
6.
PLoS One ; 19(1): e0296790, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38227598

RESUMO

SpinoCerebellar Ataxia type 7 (SCA7) is an inherited disorder caused by CAG triplet repeats encoding polyglutamine expansion in the ATXN7 protein, which is part of the transcriptional coactivator complex SAGA. The mutation primarily causes neurodegeneration in the cerebellum and retina, as well as several forebrain structures. The SCA7140Q/5Q knock-in mouse model recapitulates key disease features, including loss of vision and motor performance. To characterize the temporal progression of brain degeneration of this model, we performed a longitudinal study spanning from early to late symptomatic stages using high-resolution magnetic resonance imaging (MRI) and in vivo 1H-magnetic resonance spectroscopy (1H-MRS). Compared to wild-type mouse littermates, MRI analysis of SCA7 mice shows progressive atrophy of defined brain structures, with the striatum, thalamus and cortex being the first and most severely affected. The volume loss of these structures coincided with increased motor impairments in SCA7 mice, suggesting an alteration of the sensory-motor network, as observed in SCA7 patients. MRI also reveals atrophy of the hippocampus and anterior commissure at mid-symptomatic stage and the midbrain and brain stem at late stage. 1H-MRS of hippocampus, a brain region previously shown to be dysfunctional in patients, reveals early and progressive metabolic alterations in SCA7 mice. Interestingly, abnormal glutamine accumulation precedes the hippocampal atrophy and the reduction in myo-inositol and total N-acetyl-aspartate concentrations, two markers of glial and neuronal damage, respectively. Together, our results indicate that non-cerebellar alterations and glial and neuronal metabolic impairments may play a crucial role in the development of SCA7 mouse pathology, particularly at early stages of the disease. Degenerative features of forebrain structures in SCA7 mice correspond to current observations made in patients. Our study thus provides potential biomarkers that could be used for the evaluation of future therapeutic trials using the SCA7140Q/5Q model.


Assuntos
Ataxias Espinocerebelares , Humanos , Camundongos , Animais , Estudos Longitudinais , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/patologia , Ataxina-7/genética , Imageamento por Ressonância Magnética , Prosencéfalo/metabolismo , Espectroscopia de Ressonância Magnética , Atrofia/patologia
7.
J Prev Alzheimers Dis ; 11(1): 38-47, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38230715

RESUMO

BACKGROUND: Longitudinal changes in volumetric MRI outcome measures have been shown to correlate well with longitudinal changes in clinical instruments and have been widely used as biomarker outcomes in clinical trials for Alzheimer's disease (AD). While instances of discordant findings have been noted in some trials, especially the recent amyloid-removing therapies, the overall relationship between treatment effects on brain atrophy and clinical outcomes, and how it might depend on treatment target or mechanism, clinical instrument or imaging variable is not yet clear. OBJECTIVE: To systematically assess the consistency and therapeutic class-dependence of treatment effects on clinical outcomes and on brain atrophy in published reports of clinical trials conducted in mild cognitive impairment (MCI) and/or AD. DESIGN: Quantitative review of the published literature. The consistency of treatment effects on clinical and brain atrophy outcomes was assessed in terms of statistical agreement with hypothesized equal magnitude effects (e.g., 30% slowing of both) and nominal directional concordance, as a function of therapeutic class. SETTING: Interventional randomized clinical trials. PARTICIPANTS: MCI or AD trial participants. INTERVENTION: Treatments included were those that involved ingestion or injection of a putatively active substance into the body, encompassing both pharmacological and controlled dietary interventions. MEASUREMENTS: Each trial included in the analysis reported at least one of the required clinical outcomes (ADAS-Cog, CDR-SB or MMSE) and at least one of the required imaging outcomes (whole brain, ventricular or hippocampal volume). RESULTS: Data from 35 trials, comprising 185 pairwise comparisons, were included. Overall, the 95% confidence bounds overlapped with the line of identity for 150/185 (81%) of the imaging-clinical variable pairs. The greatest proportion of outliers was found in trials of anti-amyloid antibodies that have been shown to dramatically reduce the level of PET-detectable amyloid plaques, for which only 13/33 (39%) of observations overlapped the identity line. A Deming regression calculated using all data points yielded a slope of 0.54, whereas if data points from the amyloid remover class were excluded, the Deming regression line had a slope of 0.92. Directional discordance of treatment effects was also most pronounced for the amyloid-removing class, and for comparisons involving ventricular volume. CONCLUSION: Our results provide a frame of reference for the interpretation of clinical and brain atrophy results from future clinical trials and highlight the importance of mechanism of action in the interpretation of imaging results.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Disfunção Cognitiva/patologia , Encéfalo , Hipocampo/patologia , Atrofia/patologia
8.
Mult Scler ; 30(2): 266-271, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38235514

RESUMO

BACKGROUND: Extended interval dosing (EID) of natalizumab treatment is increasingly used in multiple sclerosis. Besides the clear anti-inflammatory effect, natalizumab is considered to have neuroprotective properties as well. OBJECTIVES: This study aimed to study the longitudinal effects of EID compared to standard interval dosing (SID) and natalizumab drug concentrations on brain atrophy. METHODS: Patients receiving EID or SID of natalizumab with a minimum radiological follow-up of 2 years were included. Changes in brain atrophy measures over time were derived from clinical routine 3D-Fluid Attenuated Inversion Recovery (FLAIR)-weighted magnetic resonance imaging (MRI) scans using SynthSeg. RESULTS: We found no differences between EID (n = 32) and SID (n = 50) for whole brain (-0.21% vs -0.16%, p = 0.42), ventricular (1.84% vs 1.13%, p = 0.24), and thalamic (-0.32% vs -0.32%, p = 0.97) annualized volume change over a median follow-up of 3.2 years. No associations between natalizumab drug concentration and brain atrophy rate were found. CONCLUSION: We found no clear evidence that EID compared to SID or lower natalizumab drug concentrations have a negative impact on the development of brain atrophy over time.


Assuntos
Doenças do Sistema Nervoso Central , Leucoencefalopatia Multifocal Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Natalizumab/uso terapêutico , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética , Atrofia/patologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Fatores Imunológicos/uso terapêutico
9.
Alzheimers Res Ther ; 16(1): 12, 2024 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238858

RESUMO

BACKGROUND: Cerebrospinal fluid (CSF) complement activation is a key part of neuroinflammation that occurs in the early stages of Alzheimer's disease (AD). However, the associations of CSF complement proteins with AD pathology, cognition, and structural neuroimaging biomarkers for AD have been rarely investigated. METHODS: A total of 210 participants (125 mild cognitive impairment [MCI] patients and 85 normal controls) were included from Alzheimer's Disease Neuroimaging Initiative (ADNI) database who measured AD pathology, cognition, and neuroimaging at baseline and every 12 months. The mixed-effect linear models were utilized to investigate longitudinal associations of CSF complement proteins with AD pathology, cognition, and neuroimaging in cognitively normal (CN) and mild cognitive impairment (MCI) subjects. Causal mediation analyses were conducted to explore the potential mediators between CSF complement proteins and cognitive changes. RESULTS: We found that the subjects with low CSF complement protein levels at baseline had worse outcomes in AD pathology, indicated by their lowest concentrations observed in A + and A + T + individuals. The reduced CSF complement proteins were associated with faster accumulation of tau among CN subjects and with cognitive decline and greater brain atrophy of specific regions among MCI subjects. Furthermore, mediation analyses showed that the effects of CSF complement proteins on cognitive performance were partially mediated by regional brain structures (mediation proportions range from 19.78 to 94.92%; p < 0.05). CONCLUSIONS: This study demonstrated that CSF complement proteins were involved in the early progression of AD. Our results indicated that regional brain atrophy might be a plausible way to connect CSF complement protein levels and cognition.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cognição , Disfunção Cognitiva/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Atrofia/patologia , Proteínas do Sistema Complemento , Proteínas tau/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano
10.
J Affect Disord ; 349: 552-558, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38195008

RESUMO

BACKGROUND: Research has estimated the associations of lifestyle at one-time point with the risk of dementia and hippocampal volume, but the impact of lifestyle transition on dementia and hippocampal volume remains unclear. This study aims to examine the associations of lifestyle transition with the risk of dementia and hippocampal volume. METHODS: Based on data from the UK Biobank, a weighted lifestyle score was constructed by incorporating six lifestyle factors. Within each baseline lifestyle group (i.e., healthy, intermediate, and unhealthy), lifestyle transition was classified into decline, maintenance, and improvement. Cox proportional hazard regression was used to estimate the association of lifestyle transition and incident dementia (N = 16,305). A multiple linear regression model was used to estimate the association between lifestyle transition and hippocampal volume (N = 5849). RESULTS: During a median follow-up period of 8.6 years, 120 (0.7 %) dementia events were documented. Among participants with healthy baseline lifestyles, the improvement group had a lower risk of incident dementia (HR: 0.18, 95 % CI: 0.04-0.81) and a larger hippocampal volume (ß = 111.69, P = 0.026) than the decline group. Similar results were observed among participants with intermediate baseline lifestyles regarding dementia risk but not hippocampal volume. No benefits were observed in the improvement group among those with unhealthy baseline lifestyles. LIMITATIONS: A lower incidence of dementia than other cohort study and this may have resulted in an underestimation of the risk of dementia. CONCLUSIONS: Earlier transitions to healthier lifestyle were associated with reduced risk of incident dementia and decreased hippocampal atrophy.


Assuntos
Demência , Estilo de Vida , Humanos , Estudos de Coortes , Demência/epidemiologia , Demência/prevenção & controle , Demência/patologia , Atrofia/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Fatores de Risco
11.
Mov Disord Clin Pract ; 11(1): 45-52, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38291837

RESUMO

BACKGROUND: RFC1-related disorder (RFC1/CANVAS) shares clinical features with other late-onset ataxias, such as spinocerebellar ataxias (SCA) and multiple system atrophy cerebellar type (MSA-C). Thinning of cranial nerves V (CNV) and VIII (CNVIII) has been reported in magnetic resonance imaging (MRI) scans of RFC1/CANVAS, but its specificity remains unclear. OBJECTIVES: To assess the usefulness of CNV and CNVIII thinning to differentiate RFC1/CANVAS from SCA and MSA-C. METHODS: Seventeen individuals with RFC1/CANVAS, 57 with SCA (types 2, 3 and 6), 11 with MSA-C and 15 healthy controls were enrolled. The Balanced Fast Field Echo sequence was used for assessment of cranial nerves. Images were reviewed by a neuroradiologist, who classified these nerves as atrophic or normal, and subsequently the CNV was segmented manually by an experienced neurologist. Both assessments were blinded to patient and clinical data. Non-parametric tests were used to assess between-group comparisons. RESULTS: Atrophy of CNV and CNVIII, both alone and in combination, was significantly more frequent in the RFC1/CANVAS group than in healthy controls and all other ataxia groups. Atrophy of CNV had the highest sensitivity (82%) and combined CNV and CNVIII atrophy had the best specificity (92%) for diagnosing RFC1/CANVAS. In the quantitative analyses, CNV was significantly thinner in the RFC1/CANVAS group relative to all other groups. The cutoff CNV diameter that best identified RFC1/CANVAS was ≤2.2 mm (AUC = 0.91; sensitivity 88.2%, specificity 95.6%). CONCLUSION: MRI evaluation of CNV and CNVIII using a dedicated sequence is an easy-to-use tool that helps to distinguish RFC1/CANVAS from SCA and MSA-C.


Assuntos
Atrofia de Múltiplos Sistemas , Ataxias Espinocerebelares , Humanos , Ataxia/patologia , Atrofia/patologia , Cerebelo/patologia , Nervos Cranianos/patologia , Atrofia de Múltiplos Sistemas/diagnóstico , Ataxias Espinocerebelares/diagnóstico
12.
J Neuroimmunol ; 387: 578280, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38171046

RESUMO

BACKGROUND: A method that can be used in the early stage of multiple sclerosis (MS) to predict the progression of brain volume loss (BVL) has not been fully established. METHODS: To develop a method of predicting progressive BVL in patients with MS (pwMS), eighty-two consecutive Japanese pwMS-with either relapsing-remitting MS (86%) or secondary progressive MS (14%)-and 41 healthy controls were included in this longitudinal retrospective analysis over an observational period of approximately 3.5 years. Using a hierarchical cluster analysis with multivariate imaging data obtained by FreeSurfer analysis, we classified the pwMS into clusters. RESULTS: At baseline and follow-up, pwMS were cross-sectionally classified into three major clusters (Clusters 1, 2, and 3) in ascending order by disability and BVL. Among the patients included in Cluster 1 at baseline, approximately one-third of patients (12/52) transitioned into Cluster 2 at follow-up. The volumes of the corpus callosum, the thalamus, and the whole brain excluding the ventricles were significantly decreased in the transition group compared with the nontransition group and were found to be the most important predictors of transition. CONCLUSION: Decreased volumes of the corpus callosum and thalamus in the relatively early stage of MS may predict the development of BVL.


Assuntos
Doenças do Sistema Nervoso Central , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Doenças Neurodegenerativas , Humanos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologia , Atrofia/etiologia , Atrofia/patologia , Tálamo/diagnóstico por imagem , Doenças Neurodegenerativas/patologia
13.
J Alzheimers Dis ; 97(3): 1341-1351, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38217601

RESUMO

BACKGROUND: Neuropsychiatric symptoms (NPS) are a common aspect of Alzheimer's disease (AD). Multiple studies have investigated its brain correlates, but it still remains unclear how they relate with brain atrophy in mild cognitive impairment (MCI). OBJECTIVE: Our objective was to investigate brain volume in MCI patients as a function of NPS. METHODS: We measured grey matter volume, neuropsychological status and NPS (Neuropsychiatric Inventory, NPI), in a sample of 81 MCI patients (43 females). Participants were divided in groups depending on presence (NPS+) or absence (NPS-) of NPS and on type of NPS. RESULTS: We found lower volume of left temporal pole in patients with depression compared to NPS- (p = 0.012), and in patients with agitation compared to NPS- in the right middle occipital gyrus (p = 0.003). We also found a significant correlation between volume of left temporal pole and MMSE (r (78) â€Š= 0.232, p = 0.019). Finally, NPS+ presented lower cross-sectional cognitive level than NPS- (t (79) â€Š= 1.79, p = 0.038), and faster cognitive decline (t (48) â€Š= -1.74, p = 0.044). CONCLUSIONS: Our results support the colocalization of structural damage as a possible mechanism underlying the relationship between MCI and depression and provide novel evidence regarding agitation. Moreover, our longitudinal evidence highlights the relevance of an adequate identification of NPS in MCI patients to identify those at risk of faster cognitive decline.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Feminino , Humanos , Depressão/diagnóstico por imagem , Estudos Transversais , Disfunção Cognitiva/diagnóstico , Doença de Alzheimer/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Atrofia/patologia , Testes Neuropsicológicos , Imageamento por Ressonância Magnética/métodos
14.
Neurobiol Aging ; 135: 70-78, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232501

RESUMO

Mounting evidence indicates marked hippocampal degeneration in semantic dementia (SD) however, the spatial distribution of hippocampal atrophy profiles in this syndrome remains unclear. Using a recently developed parcellation approach, we extracted hippocampal volumes from four distinct subregions running from anterior to posterior along the longitudinal axis (anterior, intermediate rostral, intermediate caudal, and posterior). Volumetric differences in hippocampal subregions were compared between 21 SD, 24 matched Alzheimer's disease (AD), and 27 healthy older Control participants. Despite comparable overall hippocampal volume loss, SD and AD groups diverged in terms of the magnitude of atrophy along the anterior-posterior axis of the hippocampus. Global hippocampal atrophy was observed in AD, with no discernible gradation or lateralisation. In contrast, SD patients displayed graded bilateral hippocampal atrophy, most pronounced on the left-hand side, and concentrated in anterior relative to posterior subregions. Finally, we found preliminary evidence that disease-specific vulnerability along the anterior-posterior axis of the hippocampus was associated with canonical clinical features of these syndromes.


Assuntos
Doença de Alzheimer , Demência Frontotemporal , Humanos , Doença de Alzheimer/patologia , Demência Frontotemporal/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Atrofia/patologia , Imageamento por Ressonância Magnética
15.
Ann Clin Microbiol Antimicrob ; 23(1): 4, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38217000

RESUMO

BACKGROUND AND OBJECTIVES: Helicobacter pylori (H. pylori) infection is the most common etiology of chronic gastric. H. pylori gastritis would gradually evolve into gastric atrophy, intestinal metaplasia, dysplasia and malignant lesions. Herein, this study aimed to investigate the potential impact of H. pylori colonization density and depth on the severity of histological parameters of gastritis. METHODS: A prospective monocentric study was conducted from December 2019 to July 2022, enrolling patients with confirmed chronic H. pylori infection via histopathological evaluation. H. pylori colonization status was detected by immunohistochemical staining, pathological changes of gastric specimens were detected by hematoxylin eosin staining. Epidemiological, endoscopic and histopathological data were collected. RESULTS: A total of 1120 patients with a mean age of 45.8 years were included. Regardless of the previous history of H. pylori eradication treatment, significant correlations were observed between the density and depth of H. pylori colonization and the intensity of gastritis activity (all P < 0.05). Patients with the lowest level of H. pylori colonization density and depth exhibited the highest level of mild activity. In whole participants and anti-H. pylori treatment-naive participants, H. pylori colonization density and depth were markedly correlated with the severity of chronic gastritis and gastric atrophy (all P < 0.05). H. pylori colonization density (P = 0.001) and depth (P = 0.047) were significantly associated with ulcer formation in patients naive to any anti-H. pylori treatment. No significant associations were observed between the density and depth of H. pylori colonization and other histopathological findings including lymphadenia, lymphoid follicle formation and dysplasia. CONCLUSIONS: As the density and depth of H. pylori colonization increased, so did the activity and severity of gastritis, along with an elevated risk of ulcer formation.


Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Humanos , Pessoa de Meia-Idade , Úlcera/patologia , Estudos Prospectivos , Mucosa Gástrica/patologia , Gastrite/patologia , Atrofia/patologia
16.
Sci Rep ; 14(1): 159, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167603

RESUMO

Excessive activation of poly (ADP-ribose) polymerase (PARP) contributes to ischemic acute kidney injury (AKI). PARP inhibition has been shown to be beneficial in renal ischemia-reperfusion injury (IRI) in the early phase, but its role in the repair process remains unclear. The effects of JPI-289, a novel PARP inhibitor, during the healing phase after renal IRI were investigated. IRI was performed on 9-week-old male C57BL/6 mice. Saline or JPI-289 100 mg/kg was intraperitoneally administered once at 24 h or additionally at 48 h after IRI. Hypoxic HK-2 cells were treated with JPI-289. Renal function and fibrosis extent were comparable between groups. JPI-289 treatment caused more prominent tubular atrophy and proinflammatory intrarenal leukocyte phenotypes and cytokines/chemokines changes at 12 weeks after unilateral IRI. JPI-289 treatment enhanced gene expressions associated with collagen formation, toll-like receptors, and the immune system in proximal tubules and endothelial cells after IRI. JPI-289 treatment at 3 or 6 h after hypoxia facilitated proliferation of hypoxic HK-2 cells, whereas further treatment after 24 h suppressed proliferation. Delayed inhibition of PARP after renal IRI did not facilitate the repair process during the early healing phase but rather may aggravate renal tubular atrophy during the late healing phase in ischemic AKI.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Camundongos , Animais , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Ribose , Células Endoteliais/metabolismo , Camundongos Endogâmicos C57BL , Poli(ADP-Ribose) Polimerase-1 , Isquemia/patologia , Rim/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Poli(ADP-Ribose) Polimerases/metabolismo , Traumatismo por Reperfusão/metabolismo , Atrofia/patologia
17.
Mult Scler Relat Disord ; 82: 105424, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181695

RESUMO

BACKGROUND: Enlargement of the choroid plexus (CP) is reported to associate with inflammatory activity and contribute to brain atrophy in patients with multiple sclerosis (pwMS). However, a recent study in healthy volunteers (HVTs) has suggested that CP enlargement can be attributed to ventriculomegaly. OBJECTIVES: To clarify the pathological significance of the enlargement of CP in multiple sclerosis (MS). METHODS: A total of 102 pwMS (89 with relapsing-remitting MS and 13 with secondary progressive MS) and 41 HVTs were cross-sectionally evaluated using brain volumetry. The CP volume was compared between disease groups and investigated for the relationships with other brain regional volumes. RESULTS: CP volume was significantly larger in pwMS than in HVTs in the univariate analysis, but not in multivariable analysis. Meanwhile, the CP and lateral ventricle (LV) volumes were significantly correlated. CP enlargement was significantly associated with increased lesion load and cerebral white matter (WM) atrophy, even after adjusting for LV volume. In contrast, multivariable analyses revealed that LV enlargement, but not CP enlargement, was associated with total gray matter (GM) atrophy. CONCLUSION: CP enlargement was closely associated with LV enlargement. After adjusting for LV volume, CP enlargement in pwMS was associated with increased lesion load and WM atrophy but not GM atrophy.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Substância Branca , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Plexo Corióideo/diagnóstico por imagem , Plexo Corióideo/patologia , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologia , Atrofia/patologia
18.
Transplant Proc ; 56(1): 97-104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38216361

RESUMO

AIMS AND BACKGROUND: To describe the prevalence of IgA deposits (IgAD) in renal allografts in a cohort of renal transplant recipients and to analyze their management strategies and histopathology. To assess graft function and proteinuria after 1 year of follow-up. MATERIALS AND METHODS: A prospective longitudinal follow-up study was carried out in VPS Lakeshore Hospital and Research Centre, Kochi, Kerala, over a period of 5 years (July 2015 to June 2020). Kidney transplant recipients with allograft biopsies that reported IgAD on immunofluorescence were included in the study. Light microscopy and immunofluorescence studies were performed. Mesangial hypercellularity (M); segmental glomerulosclerosis (S); endocapillary hypercellularity (E); tubular atrophy/interstitial fibrosis (T); crescents (C) (MEST-C) Scoring was done in patients with pathogenic IgAD. Treatment strategies included increased baseline steroid dosage, rituximab administration, and plasma exchange. Clinical details and management strategies were analyzed, and patients were followed up for 1 year after diagnosis. Changes in graft function (S. Creatinine) and proteinuria (Urine Protein/Creatinine ratio) were analyzed. Clinico-pathologic correlation with the MEST-C scores was also done. RESULTS: Out of 1036 kidney transplants done in the study period, 760 graft biopsies were performed. Sixty-four cases had post-transplant deposition of IgA (8%). The mean age was 45 ± 11.25SD years. The study had 51 men and 13 women. Induction immunosuppression comprised rabbit antithymocyte globulin in 29 (45%) patients and basiliximab in 35 (54%). Maintenance immunosuppression in all comprised tacrolimus, mycophenolate mofetil, and steroids. There were 2 groups: group A (pathogenic IgAD) and group B (incidental IgAD). Group A had 46 cases (71.9%), out of which 8 had "active" IgA nephropathy (endocapillary proliferation, crescents, and IgA vasculitis), and 38 had "inactive" IgAD. In patients with active deposits, 3 had cellular crescents (18%, 30%, and 23%), all 8 had endocapillary proliferation, and 2 had vasculitis. Group B had 18 cases (28.1%), comprising T cell-mediated rejections (5), antibody-mediated rejection (8), BK virus nephropathy (1), and interstitial fibrosis and tubular atrophy (4). In group A, 22 (47.8%) presented with graft dysfunction, 8 (17.3%) with isolated proteinuria, and 14 (30.4%) patients presented with a combination. Two (4.3%) patients had neither. Fourteen (30.4%) patients presented within 1 month of renal transplant. In patients of group A, at the end of 1 year of treatment, the mean S. Creatinine reduced to 1.68 mg/dL from 1.84 mg/dL, and the mean protein/creatinine ratio reduced from 1.2 to 0.5 (±1.17). In patients with "active IgA" lesions, at the end of 1 year of treatment, the mean S. Creatinine increased slightly to 1.68 mg/dL (±0.47SD) from 1.48 mg/dL (±0.52SD), and the mean protein/creatinine ratio reduced from 2.32 (±1.56SD) to 1.05 (±1.70SD). In the 16 patients with IgAD and proteinuria, at the end of 1 year of treatment, the mean S. Creatinine decreased to 1.41 ± 0.32 SD mg/dL from 1.47±0.37SD mg/dL and the mean protein/creatinine ratio reduced from 1.12 ± 1.31 SD to 0.39±0.75 SD. In the remaining 22 patients with acute tubular injury, at the end of 1 year, the mean S. Creatinine decreased to 1.920.32 SD mg/dL from 2.10.8SD mg/dL, and the mean protein/creatinine ratio reduced from 1.1 ± 1.31 SD to 0.66 ± 1.45 SD. In the MEST-C scoring analysis, all scores were 0 in 20 (43.4%) biopsies, only M1 score in 11 (23.9%) biopsies, only E1 score in 10 biopsies (21.7%), S1 in 13 (28.2%) cases. CONCLUSION: Immunoglobulin A deposits occur commonly after transplant; these may represent recurrence, de novo IgA, or donor-derived IgAD. Although commonly benign, some may cause significant graft dysfunction and graft loss. IgAD can present as varying combinations of graft dysfunction and proteinuria. Active IgA pathologies may occur early in the post-transplant course, may have significant graft dysfunction, and need proactive management. There is a correlation between segmental sclerosis and proteinuria. Evidence for the efficacy of Rituximab, plasma exchange, and prolonged courses of steroids is wanting; however, some benefits are possible. Long-term follow-up is essential.


Assuntos
Glomerulonefrite por IGA , Transplante de Rim , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Rituximab/uso terapêutico , Estudos Prospectivos , Creatinina , Seguimentos , Rim/patologia , Glomerulonefrite por IGA/patologia , Proteinúria/etiologia , Imunoglobulina A , Esteroides/uso terapêutico , Fibrose , Aloenxertos/patologia , Atrofia/patologia , Biópsia/efeitos adversos
19.
Cell ; 187(4): 882-896.e17, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38295787

RESUMO

Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus. Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.


Assuntos
Gastrite , Neoplasias Gástricas , Infecções Estreptocócicas , Streptococcus anginosus , Animais , Humanos , Camundongos , Atrofia/patologia , Carcinogênese , Transformação Celular Neoplásica , Mucosa Gástrica , Gastrite/patologia , Inflamação/patologia , Proteínas Quinases Ativadas por Mitógeno , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Streptococcus anginosus/fisiologia , Infecções Estreptocócicas/patologia
20.
J Neurol Sci ; 457: 122894, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266517

RESUMO

BACKGROUND: The influence of limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathological change (LATE-NC) on structural alterations in argyrophilic grain disease (AGD) have not been documented. This study aimed to investigate the morphological impact of LATE-NC on AGD through voxel-based morphometry (VBM) technique. MATERIALS AND METHODS: Fifteen individuals with pathologically verified AGD, comprising 6 with LATE-NC (comorbid AGD [cAGD]) and 9 without LATE-NC (pure AGD [pAGD]), along with 10 healthy controls (HC) were enrolled. Whole-brain 3D-T1-weighted images were captured and preprocessed utilizing the Computational Anatomy Toolbox 12. VBM was employed to compare gray matter volume among (i) pAGD and HC, (ii) cAGD and HC, and (iii) pAGD and cAGD. RESULTS: In comparison to HC, the pAGD group exhibited slightly asymmetric gray matter volume loss, particularly in the ambient gyrus, amygdala, hippocampus, anterior cingulate gyrus, and insula. Alternatively, the cAGD group exhibited greater gray matter volume loss, with a predominant focus on the inferolateral regions encompassing the ambient gyrus, amygdala, hippocampus, and the inferior temporal area, including the anterior temporal pole. The atrophy of the bilateral anterior temporal pole and right inferior temporal gyrus persisted when contrasting the pAGD and cAGD groups. CONCLUSION: Comorbidity with LATE-NC is linked to different atrophic distribution, particularly affecting the inferolateral regions in AGD. Consequently, the consideration of comorbid LATE-NC is crucial in individuals with AGD exhibiting more widespread temporal atrophy.


Assuntos
Demência , Doenças Neurodegenerativas , Proteinopatias TDP-43 , Humanos , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Demência/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Imageamento por Ressonância Magnética/métodos , Doenças Neurodegenerativas/patologia , Proteinopatias TDP-43/patologia
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