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1.
Nat Rev Neurol ; 16(3): 171-182, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32094485

RESUMO

Early evaluation of treatment response and prediction of disease evolution are key issues in the management of people with multiple sclerosis (MS). In the past 20 years, MRI has become the most useful paraclinical tool in both situations and is used clinically to assess the inflammatory component of the disease, particularly the presence and evolution of focal lesions - the pathological hallmark of MS. However, diffuse neurodegenerative processes that are at least partly independent of inflammatory mechanisms can develop early in people with MS and are closely related to disability. The effects of these neurodegenerative processes at a macroscopic level can be quantified by estimation of brain and spinal cord atrophy with MRI. MRI measurements of atrophy in MS have also been proposed as a complementary approach to lesion assessment to facilitate the prediction of clinical outcomes and to assess treatment responses. In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group critically review the application of brain and spinal cord atrophy in clinical practice in the management of MS, considering the role of atrophy measures in prognosis and treatment monitoring and the barriers to clinical use of these measures. On the basis of this review, the group makes consensus statements and recommendations for future research.


Assuntos
Encéfalo/patologia , Consenso , Imagem por Ressonância Magnética/normas , Esclerose Múltipla/diagnóstico por imagem , Guias de Prática Clínica como Assunto/normas , Índice de Gravidade de Doença , Medula Espinal/diagnóstico por imagem , Atrofia/diagnóstico por imagem , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética/métodos , Esclerose Múltipla/patologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Medula Espinal/patologia
2.
Am J Forensic Med Pathol ; 41(1): 32-34, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32000220

RESUMO

Thymus glands from 283 autopsy cases were sampled and evaluated with histochemical and immunohistochemical methods. A subpopulation of 41 intravenous drug addicts were compared with age-matched control cases.It was found that an accelerated involution of the thymus occurred in the 20- to 25-year interval and thereafter with a steady pace of 5% per year. Also the size of Hassall bodies declined successively.In drug addicts, an increased dystrophic calcification of the Hassall bodies and a significant difference in thymus size (atrophy) compared with controls were seen. Moreover, a difference was seen in the relative numbers of CD4 and CD8 lymphocytes where CD4+ cells were reduced in drug addicts.It is hypothesized that signs of hepatitis C virus infection that was found in the majority of drug addicts and the reduced number of functionally intact Hassall corpuscles could explain the reduction of CD4+ lymphocytes and thymic hypotrophy in this population.


Assuntos
Usuários de Drogas , Abuso de Substâncias por Via Intravenosa , Timo/patologia , Adolescente , Adulto , Envelhecimento/patologia , Atrofia/patologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Calcinose/patologia , Estudos de Casos e Controles , Feminino , Patologia Legal , Hepatite C Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
3.
Nat Commun ; 11(1): 411, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964863

RESUMO

Alzheimer's disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-ß (Aß) via its N-terminal Aß binding domain, and facilitates Aß aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD.


Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva/genética , Proteínas do Tecido Nervoso/genética , Placa Amiloide/genética , Agregação Patológica de Proteínas/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Animais , Atrofia/diagnóstico por imagem , Atrofia/genética , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/patologia , Conjuntos de Dados como Assunto , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Placa Amiloide/patologia , Polimorfismo de Nucleotídeo Único , Agregação Patológica de Proteínas/diagnóstico por imagem , Agregação Patológica de Proteínas/patologia
4.
Neurology ; 94(3): e323-e329, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31848256

RESUMO

OBJECTIVE: To determine the temporal evolution, morphology, and frequency of macular ganglion cell atrophy in patients with retrochiasmal lesions of the visual pathway. METHODS: In a consecutive retrospective case series, we identified 47 patients with homonymous hemianopia and accessible macular optical coherence tomography scans. We estimated the time of lesion onset and the location of the lesion within the afferent visual pathway. Using semiautomatic layer segmentation, we determined ganglion cell layer thickness in areas projecting to the side of the retrochiasmal lesion and compared it with ganglion cell layer thickness on the healthy side. RESULTS: We found that retrochiasmal lesions at any level may be associated with an atrophy of ganglion cells. This atrophy respects the vertical midline through the fovea and thus the anatomic separation of the nasal and temporal visual field. The vertical line separating the affected from the unaffected side has significantly less tilt as compared with the disc-fovea angle. Lesions of the optic tract are associated with earlier macular ganglion cell atrophy than retrogeniculate lesions. Macular ganglion cell atrophy may be present in cases with normal peripapillary nerve fiber layer analysis and vice versa. CONCLUSIONS: Macular ganglion cell layer thickness shows a topographic hemiatrophy in retrochiasmal lesions, which manifests earlier for tract lesions than for retrogeniculate lesions. This additional examination of ganglion cell homonymous hemiatrophy has a higher sensitivity in detecting retrograde transsynaptic degeneration than the analysis of the peripapillary nerve fiber layer alone.


Assuntos
Hemianopsia/patologia , Células Ganglionares da Retina/patologia , Vias Visuais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
5.
Nat Commun ; 10(1): 5815, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31862889

RESUMO

Locomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy.


Assuntos
Locomoção/fisiologia , Neurônios Motores/fisiologia , Fatores de Crescimento Neural/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Animais , Atrofia/patologia , Atrofia/fisiopatologia , Dendritos/patologia , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Neurônios Motores/patologia , Vias Neurais/fisiopatologia , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/patologia
6.
Horm Mol Biol Clin Investig ; 41(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31855563

RESUMO

The purpose of this publication is to summarize the results of the vaginal erbium:yttrium-aluminum-garnet (Er:YAG) Smooth® laser (VEL) on the vaginal atrophy component of the genitourinary syndrome of menopause (GSM). GSM has two categories of clinical signs related to estrogen deficiency: symptoms of vulvovaginal atrophy (VVA) and urinary symptoms. This symptomatology is chronic, progressive over the years and affects a majority of women concerned by natural menopause but not exclusively: we must also consider the growing number of survivors of gynecological or non-gynecological cancers (breast, cervix, uterus, vagina, anus, etc.). At a time when hormonal treatment of menopause is contested as is the installation of under urethra prosthesis, the innovation provided by the VEL technology has the merit of offering the women concerned an effective therapeutic alternative with the security of a patent. The VEL technology has an original and unique process: acting only by thermal effect and not by ablation on tissue, VEL is a safe solution in terms of side effects and potential complications. Studies have been increasing since 2012 and all demonstrate a significant improvement in the GSM signs and symptoms, as well as an improved sexual life after VEL treatment. Double-blind, placebo-controlled, randomized studies are expected in order to ultimately confirm the safety and effectiveness of VEL.


Assuntos
Terapia a Laser/métodos , Lasers de Estado Sólido/uso terapêutico , Vagina/cirurgia , Doenças Vaginais/cirurgia , Animais , Atrofia/patologia , Atrofia/cirurgia , Feminino , Humanos , Menopausa , Vagina/patologia , Doenças Vaginais/patologia
7.
EMBO J ; 38(23): e101982, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31633821

RESUMO

Cellular senescence has been shown to contribute to skin ageing. However, the role of melanocytes in the process is understudied. Our data show that melanocytes are the only epidermal cell type to express the senescence marker p16INK4A during human skin ageing. Aged melanocytes also display additional markers of senescence such as reduced HMGB1 and dysfunctional telomeres, without detectable telomere shortening. Additionally, senescent melanocyte SASP induces telomere dysfunction in paracrine manner and limits proliferation of surrounding cells via activation of CXCR3-dependent mitochondrial ROS. Finally, senescent melanocytes impair basal keratinocyte proliferation and contribute to epidermal atrophy in vitro using 3D human epidermal equivalents. Crucially, clearance of senescent melanocytes using the senolytic drug ABT737 or treatment with mitochondria-targeted antioxidant MitoQ suppressed this effect. In conclusion, our study provides proof-of-concept evidence that senescent melanocytes affect keratinocyte function and act as drivers of human skin ageing.


Assuntos
Envelhecimento/patologia , Atrofia/patologia , Senescência Celular , Melanócitos/patologia , Pele/patologia , Telômero/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/efeitos dos fármacos , Atrofia/induzido quimicamente , Células Cultivadas , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/patologia , Feminino , Humanos , Masculino , Melanócitos/metabolismo , Pessoa de Meia-Idade , Comunicação Parácrina , Espécies Reativas de Oxigênio/metabolismo , Receptores CXCR4/metabolismo , Pele/metabolismo , Telômero/metabolismo , Adulto Jovem
8.
An Bras Dermatol ; 94(4): 473-475, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644625

RESUMO

Atrophoderma of Pasini and Pierini is a skin disorder affecting dermal collagen and is clinically characterized by well-defined plaques of depressed skin. Histopathological changes are subtle, and in most cases, the diagnosis requires a comparative study with healthy skin from the same anatomical site. High frequency ultrasound is a useful imaging method for diagnosis of atrophic skin changes. A case is presented in which ultrasound can support the clinical and the histopathological diagnosis of atrophoderma of Pasini and Pierini.


Assuntos
Derme/diagnóstico por imagem , Derme/patologia , Dermatopatias/diagnóstico por imagem , Dermatopatias/patologia , Ultrassonografia Doppler em Cores/métodos , Adulto , Atrofia/diagnóstico por imagem , Atrofia/patologia , Biópsia , Diagnóstico Precoce , Feminino , Humanos
9.
Arch. Soc. Esp. Oftalmol ; 94(9): 465-468, sept. 2019. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-186228

RESUMO

Mujer de 67 años con diabetes mellitus tipo 2 sin otros antecedentes de interés que consultó por disminución de agudeza visual de su ojo izquierdo de 4 meses de evolución. El examen de fondo de ojo reveló datos de retinopatía diabética no proliferativa moderada en el ojo derecho y lesiones pigmentadas en forma de espículas óseas y atrofia del epitelio pigmentario retiniano en la media periferia y en el área macular en el ojo izquierdo. El electrorretinograma de campo completo se mostró plano, con una insinuación leve de la onda b en adaptación a la luz con destello único de 3,0cd en el ojo izquierdo. En la tomografía de coherencia óptica se vio la retina atrófica en todas sus capas, quistes intrarretinianos y un desprendimiento neurosensorial seroso de la retina macular con una lesión subretiniana de alta reflectividad en el ojo izquierdo. Fueron descartadas causas infecciosas e inflamatorias. Se administraron 3 inyecciones de ranibizumab intravítreo con periodicidad mensual. La presencia de membrana neovascular coroidea asociada con retinitis pigmentosa unilateral no ha sido publicada previamente. El presente caso respondió a ranibizumab intravítreo


A 67 year-old woman with diabetes mellitus type 2 no medical background of interest was attended in hospital due to visual loss of left eye of 4 months of onset. The fundus examination revealed findings corresponding to moderate non-proliferative diabetic retinopathy in the right eye and pigmented lesions similar to bone spicules and atrophy of the retinal pigment epithelium in the middle periphery and in the macular area in the left eye. The full-field electroretinogram was flat, with a slight insinuation of the b-wave in the light adaptation with a single flash of 3.0cd in the left eye. The optical coherence tomography showed the atrophic retina in all its layers, as well as intraretinal cysts and a serous neurosensory detachment of the macular retina with a lesion of high reflectivity in the left eye. Infectious and inflammatory diseases were ruled out. Three doses of intravitreal ranibizumab were administered monthly. The presence of choroidal neovascular membrane associated with unilateral retinitis pigmentosa has not been previously reported. The patient improved with intravitreal ranibizumab


Assuntos
Humanos , Feminino , Idoso , Neovascularização de Coroide/etiologia , Retinite Pigmentosa/complicações , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Atrofia/patologia , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/tratamento farmacológico , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico por imagem , Eletrorretinografia , Angiofluoresceinografia , Injeções Intravítreas , Ranibizumab/administração & dosagem , Ranibizumab/uso terapêutico , Epitélio Pigmentado da Retina/patologia , Retinite Pigmentosa/diagnóstico por imagem , Tomografia de Coerência Óptica
10.
J Clin Neurosci ; 69: 279-280, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31447362

RESUMO

A 23-year old man was found to have a Chiari Type 1 malformation and cerebellar atrophy. While this association has previously been described, the remote cerebellar atrophy is difficult to explain. We believe the answer lies with our finding of signal hyperintensity on MR imaging at the level of the inferior olives. This suggest hypertrophic olivary degeneration, caused by trans-synaptic degeneration following disruption to the Guillain-Mollaret triangle. Propagation of this process to the cerebellar Purkinje cells occurs in some cases. We describe a case in support of this hypothesis and review previously published evidence.


Assuntos
Malformação de Arnold-Chiari/patologia , Doenças Cerebelares/patologia , Núcleo Olivar/patologia , Degeneração Retrógrada/patologia , Malformação de Arnold-Chiari/complicações , Atrofia/patologia , Doenças Cerebelares/etiologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Adulto Jovem
11.
BMC Neurosci ; 20(1): 39, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375091

RESUMO

BACKGROUND: Amblyopia is generally considered a neurodevelopmental disorder that results from abnormal visual experiences in early childhood and may persist to adulthood. The neural basis of amblyopia has been a matter of interest for many decades, but the critical neural processing sites in amblyopia are not entirely understood. Although many functional neuroimaging studies have found abnormal neuronal responses both within and beyond V1, few studies have focused on the neurophysiologic abnormalities in the visual cortex from the viewpoint of potential structural reorganization. In this study, we used a well-validated and highly accurate surface-based method to examine cortical morphologic changes in the visual cortex using multiple parameters (including cortical thickness, surface area, volume and mean curvature). RESULTS: The cortical thicknesses of the bilateral V1, left V2, left ventral V3, left V4 and left V5/MT+ in patients were significantly thinner than that in controls. The mean curvature of the bilateral V1 was significantly increased in the patients compared with the controls. For the surface area and gray matter volume, no significant differences were found between patients and controls in all region of interests. The cortical thicknesses of the bilateral V1 were both negatively correlated with the amount of anisometropia. No significant correlations were found between any other surface parameters and clinical variables. CONCLUSION: In addition to cortical thickness, the altered mean curvature of the cortex may indicate neuroanatomic impairments of the visual cortex in patients with anisometropic amblyopia. Moreover, the structural changes were bilateral in the primary visual cortex but were unilateral in the secondary and more senior visual cortex.


Assuntos
Ambliopia/patologia , Córtex Visual/patologia , Adulto , Atrofia/patologia , Estudos de Casos e Controles , Feminino , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Adulto Jovem
12.
Int J Dermatol ; 58(9): 1078-1082, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31373397

RESUMO

BACKGROUND: DNA promoter methylation is usually an early stage in carcinogenesis process, including oral cancer. The purpose of this study was to investigate the association between T allele of specific single nucleotide polymorphism (SNP) C>T rs 16906252 and O16-methylguanine-DNA methyltransferase (MGMT) methylation as prospective biomarkers of malignant transformation in oral lichen planus (OLP), a chronic autoimmune mucocutaneous disease. METHODS: This research is an observational, analytical case-control study where a total of 85 subjects (43 control individuals and 42 OLP patients) participated. The samples (mouthwashes) from all volunteers were analyzed, and DNA extraction was carried out. The genotyping of the rs 16906252 SNP in the MGMT gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses of Student t test and multiple logistic regressions were used. RESULTS: C>T genotype in the control and OLP groups was detected in 2.3% and 19.0%, respectively. The presence of this genotype was associated with methylation of the MGMT gene. In fact, taking into account age and gender, subjects with C>T genotype were 10.5 (95% CI 1.03-106; P = 0.047) times more likely to methylate promoter region of the MGMT gene. CONCLUSIONS: These findings indicate that C>T allele of rs 16906252, predictor of MGMT promoter methylation status, may be an important feature in the clinical prognosis of premalignant lesions of OLP, although this finding requires further clinical and laboratory investigation.


Assuntos
Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Líquen Plano Bucal/patologia , Mucosa Bucal/patologia , Lesões Pré-Cancerosas/diagnóstico , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Alelos , Atrofia/diagnóstico , Atrofia/genética , Atrofia/patologia , Biomarcadores , Estudos de Casos e Controles , Progressão da Doença , Feminino , Técnicas de Genotipagem , Humanos , Líquen Plano Bucal/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Prognóstico , Regiões Promotoras Genéticas/genética
13.
Neurology ; 93(9): e864-e878, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31363056

RESUMO

OBJECTIVE: Adiposity predictors, body mass index (BMI), waist circumference (WC), and blood leptin and total adiponectin levels were associated with components of cerebral small vessel disease (CSVD) and brain volumetry in 503 adults with CSVD who were ≥50 years of age and enrolled in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC). METHODS: RUN DMC participants were followed up for 9 years (2006-2015). BMI, WC, brain imaging, and dementia diagnoses were evaluated at baseline and follow-up. Adipokines were measured at baseline. Brain imaging outcomes included CSVD components, white matter hyperintensities, lacunes, microbleeds, gray and white matter, hippocampal, total brain, and intracranial volumes. RESULTS: Cross-sectionally among men at baseline, higher BMI, WC, and leptin were associated with lower gray matter and total brain volumes, and higher BMI and WC were associated with lower hippocampal volume. At follow-up 9 years later, higher BMI was cross-sectionally associated with lower gray matter volume, and an obese WC (>102 cm) was protective for ≥1 lacune or ≥1 microbleed in men. In women, increasing BMI and overweight or obesity (BMI ≥25 kg/m2 or WC >88 cm) were associated with ≥1 lacune. Longitudinally, over 9 years, a baseline obese WC was associated with decreasing hippocampal volume, particularly in men, and increasing white matter hyperintensity volume in women and men. CONCLUSIONS: Anthropometric and metabolic adiposity predictors were differentially associated with CSVD components and brain volumetry outcomes by sex. Higher adiposity is associated with a vascular-neurodegenerative spectrum among adults at risk for vascular forms of cognitive impairment and dementias.


Assuntos
Adiposidade , Encéfalo/patologia , Adiponectina/sangue , Idoso , Idoso de 80 Anos ou mais , Atrofia/patologia , Índice de Massa Corporal , Encéfalo/irrigação sanguínea , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/patologia , Estudos Transversais , Feminino , Seguimentos , Substância Cinzenta/patologia , Hipocampo/patologia , Humanos , Leptina/sangue , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Obesidade/sangue , Obesidade/complicações , Obesidade/patologia , Sobrepeso/sangue , Sobrepeso/complicações , Sobrepeso/patologia , Fatores de Risco , Fatores Sexuais , Circunferência da Cintura , Substância Branca/patologia
14.
World J Gastroenterol ; 25(30): 4105-4124, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31435167

RESUMO

Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis, due largely to late diagnosis. The importance of the interaction between Helicobacter pylori (H. pylori) infection, the main risk factor, and host-related genetic factors has been studied intensively in recent years. The genetic predisposition for non-hereditary gastric cancer is difficult to assess, as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined. For non-cardiac intestinal-type cancer, identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies. The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H. pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia; the literature now includes various and non-conclusive results on this topic. The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions. Among the investigated gene variants onlyIL10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk. One of the most important limiting factors is the inhomogeneity of the studies (e.g., the lack of data on concomitant H. pylori infection, methods used to assess preneoplastic lesions, and source population). Testing the modifying effect of H. pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions, or even testing the interaction between H. pylori and cytokine gene variants in multivariable models adjusted for potential covariates, could increase generalizability of results.


Assuntos
Citocinas/genética , Mucosa Gástrica/patologia , Infecções por Helicobacter/epidemiologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Atrofia/epidemiologia , Atrofia/etiologia , Atrofia/patologia , Progressão da Doença , Mucosa Gástrica/microbiologia , Predisposição Genética para Doença , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Metaplasia/epidemiologia , Metaplasia/etiologia , Metaplasia/patologia , Polimorfismo de Nucleotídeo Único , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia
15.
Exp Neurol ; 321: 113040, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31445042

RESUMO

Traumatic brain injury (TBI) often damages axons in white matter tracts and causes corpus callosum (CC) atrophy in chronic TBI patients. Injured axons encounter irreversible damage if transected, or alternatively may maintain continuity and subsequently either recover or degenerate. Secondary mechanisms can cause further axon damage, myelin pathology, and neuroinflammation. Molecular mechanisms regulating the progression of white matter pathology indicate potential therapeutic targets. SARM1 is essential for execution of the conserved axon death pathway. We examined white matter pathology following mild TBI with CC traumatic axonal injury in mice with Sarm1 gene deletion (Sarm1-/-). High resolution ultrastructural analysis at 3 days post-TBI revealed dramatically reduced axon damage in Sarm1-/- mice, as compared to Sarm1+/+ wild-type controls. Sarm1 deletion produced larger axons with thinner myelin, and attenuated TBI induced demyelination, i.e. myelin loss along apparently intact axons. At 6 weeks post-TBI, Sarm1-/- mice had less demyelination and thinner myelin than Sarm1+/+ mice, but axonal protection was no longer observed. We next used Thy1-YFP crosses to assess Sarm1 involvement in white matter neurodegeneration and neuroinflammation at 8 weeks post-TBI, when significant CC atrophy indicates chronic pathology. Thy1-YFP expression demonstrated continued CC axon damage yet absence of overt cortical pathology. Importantly, significant CC atrophy in Thy1-YFP/Sarm1+/+ mice was associated with reduced neurofilament immunolabeling of axons. Both effects were attenuated in Thy1-YFP/Sarm1-/- mice. Surprisingly, Thy1-YFP/Sarm1-/- mice had increased CC astrogliosis. This study demonstrates that Sarm1 inactivation reduces demyelination, and white matter atrophy after TBI, while the post-injury stage impacts when axon protection is effective.


Assuntos
Proteínas do Domínio Armadillo/deficiência , Lesões Encefálicas Traumáticas/patologia , Proteínas do Citoesqueleto/deficiência , Doenças Desmielinizantes/patologia , Substância Branca/patologia , Animais , Atrofia/metabolismo , Atrofia/patologia , Axônios/metabolismo , Axônios/patologia , Lesões Encefálicas Traumáticas/metabolismo , Doenças Desmielinizantes/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Substância Branca/metabolismo
16.
An. bras. dermatol ; 94(4): 473-475, July-Aug. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1038301

RESUMO

Abstract: Atrophoderma of Pasini and Pierini is a skin disorder affecting dermal collagen and is clinically characterized by well-defined plaques of depressed skin. Histopathological changes are subtle, and in most cases, the diagnosis requires a comparative study with healthy skin from the same anatomical site. High frequency ultrasound is a useful imaging method for diagnosis of atrophic skin changes. A case is presented in which ultrasound can support the clinical and the histopathological diagnosis of atrophoderma of Pasini and Pierini.


Assuntos
Humanos , Feminino , Adulto , Dermatopatias/patologia , Dermatopatias/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Derme/patologia , Derme/diagnóstico por imagem , Atrofia/patologia , Atrofia/diagnóstico por imagem , Biópsia , Diagnóstico Precoce
17.
Neurology ; 93(8): e766-e777, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31320470

RESUMO

OBJECTIVE: To evaluate the associations of mild behavioral impairment (MBI) with cognitive deficits and patterns of gray matter changes in Parkinson disease (PD). METHODS: Sixty patients with PD without dementia and 29 healthy controls underwent a cognitive neuropsychological evaluation and structural MRI scan. MBI was evaluated with the MBI Checklist (MBI-C), a rating scale designed to elicit emergent neuropsychiatric symptoms in accordance with MBI criteria. We divided the patients with PD into 2 groups: 1 group with high MBI-C scores (PD-MBI) and the other with low MBI-C scores (PD-noMBI). RESULTS: Among 60 patients with PD, 20 were categorized as having PD-MBI (33.33%). In healthy controls, no participants met the MBI cut-point threshold. The PD-MBI group had significantly lower Montreal Cognitive Assessment and z scores in all 5 domains and the global score compared to healthy controls and those with PD-noMBI. In addition, all cognitive domains except language and global cognition negatively correlated with the MBI-C total score in all patients with PD. For cortical structures, the PD-MBI group revealed middle temporal cortex thinning and decreased volume compared with the PD-noMBI group, and decreased volume in this area negatively correlated with the MBI-C total score. CONCLUSIONS: The impaired cognitive function over all domains and atrophy in the temporal area in the PD-MBI group are in line with posterior cortical circuit deficits in PD, which have been associated with a faster rate of progression to dementia. These initial results suggest that MBI might be an early and important marker for incident cognitive decline and dementia in patients with PD.


Assuntos
Disfunção Cognitiva/patologia , Substância Cinzenta/patologia , Doença de Parkinson/patologia , Doença de Parkinson/psicologia , Comportamento Problema/psicologia , Lobo Temporal/patologia , Idoso , Idoso de 80 Anos ou mais , Atrofia/patologia , Estudos de Casos e Controles , Disfunção Cognitiva/complicações , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Testes Neuropsicológicos , Doença de Parkinson/complicações
18.
Neurology ; 93(7): e628-e634, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31289142

RESUMO

OBJECTIVE: Progressive motor impairment anatomically attributable to a single critical demyelinating lesion on eloquent corticospinal tract locations occurs in progressive solitary sclerosis and in some patients with multiple sclerosis (MS) with highly restricted CNS lesion burden (2-5 lesions). We determined whether a similar critical lesion is found in patients with MS with unilateral motor progression and unlimited lesion burden. METHODS: In this observational study, we retrospectively identified Mayo Clinic patients (January 1, 1996-December 31, 2017) with an MS diagnosis (2017 McDonald criteria), ≥1 year of exclusively unilateral motor progression, and >5 demyelinating lesions on MRI. A blinded neuroradiologist identified a single critical lesion (last available MRI) based on prominent size, atrophy, and eloquent corticospinal tract location (spinal cord lateral columns, medullary pyramids, cerebral peduncles, internal capsules). We then determined whether the motor impairment was anatomically attributable to the identified lesion. RESULTS: Thirty-eight patients with MS were included: 20 (53%) with primary progressive MS and 18 (47%) with secondary progressive MS. Median age at progression onset was 54 (range 39-73) years. Median Expanded Disability Status Scale score was 5 (range 2.5-7.5) at the last follow-up (median 132.5 months from symptom onset, range 23-390 months). A single critical lesion was identified in 25 of 38 cases (66%): 19 in the cervical cord and 6 in the thoracic cord. In the remaining patients, >1 potential critical lesions were present. The overall probability to detect demyelinating lesions was higher along the corticospinal tract where the motor deficit localized (38 of 38 [100%]) than on the contralateral side (15 of 38 [39%]) (p < 0.0001). CONCLUSIONS: In patients with MS with unilateral motor progression, the motor deficit may be attributable to a single critical corticospinal tract lesion.


Assuntos
Atrofia/patologia , Encéfalo/patologia , Esclerose Múltipla/patologia , Tratos Piramidais/patologia , Adulto , Idoso , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose/patologia
19.
Helicobacter ; 24(5): e12605, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31304663

RESUMO

BACKGROUND: The diagnosis of gastric atrophy is important in the regions where the prevalence of Helicobacter pylori (H. pylori) is high. The assessment of gastric atrophy is impossible in subjects with severe gastric inflammation or inadequate biopsy samples, leading these cases to be categorized as indefinite for atrophy. The aim of this study was to evaluate clinical characteristics of cases reported as indefinite for atrophy. MATERIALS AND METHODS: We reviewed 3192 gastric biopsies obtained at a single medical center between 2003 and 2017. Cases categorized as indefinite atrophy (n = 1,292) were compared with three groups, the absent atrophy group (n = 755), Operative Link on Gastric Atrophy (OLGA) I-II group (n = 925), and OLGA III-IV group (n = 220), by considering age, sex, smoking, alcohol drinking, salty and spicy food diet, ABO blood type, family history of gastric cancer (GC), and H. pylori infection that are known atrophic gastritis-associated risk factors. RESULTS: Subjects aged ≥65 years (34.9% vs 26.4%, P < 0.001), male (58.9% vs 49.1%, P < 0.001), and H. pylori infected subjects (82.5% vs 63.3%, P < 0.001) were significantly more likely to be categorized into the indefinite atrophy group than absent atrophy group. Subjects with family history of GC (21.9% vs 25.7%, P = 0.031) and positive H. pylori infection (82.5% vs 86.2%, P = 0.019) were significantly less likely to be in the indefinite atrophy group than low-risk OLGA group. Subjects aged ≥65 years (34.9% vs 52.3%, P < 0.001) and current/past smoker (50.9% vs 70.0%, P < 0.001) were significantly more likely to be in the high-risk OLGA group than indefinite atrophy group. CONCLUSIONS: The pathological report of indefinite for atrophy suggests a higher plausibility of gastric atrophy than nonassessment due to a simple technical error.


Assuntos
Atrofia/diagnóstico , Atrofia/patologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Idoso , Idoso de 80 Anos ou mais , Atrofia/epidemiologia , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
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