Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
Int J Mol Sci ; 24(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37445606

RESUMO

Marfan syndrome (MFS) is an autosomal dominant disorder caused by a heterozygous mutation of the FBN1 gene. MFS patients present oxidative stress that disturbs redox homeostasis. Redox homeostasis depends in part on the enzymatic antioxidant system, which includes thioredoxin reductase (TrxR) and glutathione peroxidases (GPx), both of which require an adequate concentration of selenium (Se). Therefore, the aim of this study was to determine if Se levels are decreased in the TAA of patients with MFS since this could contribute to the formation of an aneurysm in these patients. The results show that interleukins IL-1ß, IL-6 TGF-ß1, and TNF-α (p ≤ 0.03), and carbonylation (p ≤ 0.03) were increased in the TAA of patients with MFS in comparison with control subjects, while Se, thiols (p = 0.02), TrxR, and GPx (p ≤ 0.001) were decreased. TLR4 and NOX1 (p ≤ 0.03), MMP9 and MMP2 (p = 0.04) and NOS2 (p < 0.001) were also increased. Therefore, Se concentrations are decreased in the TAA of MFS, which can contribute to a decrease in the activities of TrxR and GPx, and thiol groups. A decrease in the activities of these enzymes can lead to the loss of redox homeostasis, which can, in turn, lead to an increase in the pro-inflammatory interleukins associated with the overexpression of MMP9 and MMP2.


Assuntos
Aneurisma , Síndrome de Marfan , Selênio , Humanos , Aorta Torácica , Tiorredoxina Dissulfeto Redutase , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Aneurisma/complicações , Glutationa Peroxidase
2.
Am J Pathol ; 191(2): 294-308, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33159886

RESUMO

Inflammation and oxidative stress accompany aging. This study investigated the interplay between oxidative stress and inflammation in the lacrimal gland. C57BL/6 mice were used at 2 to 3, 12, and 24 months of age. Nuclear factor erythroid derived-2-related factor 2 (Nrf2)-/- and corresponding wild-type mice were used at 2 to 3 and 12 to 13 months of age. A separate group of 15.5 to 17 months of age C57BL/6 mice received a diet containing an Nrf2 inducer (Oltipraz) for 8 weeks. Aged C57BL/6 lacrimal glands showed significantly greater lymphocytic infiltration, higher levels of MHC II, IFN-γ, IL-1ß, TNF-α, and cathepsin S (Ctss) mRNA transcripts, and greater nitrotyrosine and 4-hydroxynonenal protein. Young Nrf2-/- mice showed an increase in IL-1ß, IFN-γ, MHC II, and Ctss mRNA transcripts compared with young wild-type mice and greater age-related changes at 12 to 13 months of age. Oltipraz diet significantly decreased nitrotyrosine and 4-hydroxynonenal and decreased the expression of IL-1ß and TNF-α mRNA transcripts, while decreasing the frequency of CD45+CD4+ cells in lacrimal glands and significantly increasing conjunctival goblet cell density compared with a standard diet. The findings provide novel insight into the development of chronic, low-grade inflammation and oxidative stress in age-related dry eye. New therapies targeting oxidative stress pathways will be valuable in treating age-related dry eye.


Assuntos
Envelhecimento/patologia , Síndromes do Olho Seco/patologia , Aparelho Lacrimal/patologia , Estresse Oxidativo/fisiologia , Envelhecimento/metabolismo , Animais , Síndromes do Olho Seco/imunologia , Síndromes do Olho Seco/metabolismo , Feminino , Inflamação , Aparelho Lacrimal/imunologia , Aparelho Lacrimal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pirazinas/farmacologia , Tionas/farmacologia , Tiofenos/farmacologia
3.
Gac Med Mex ; 158(6): 369-375, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36657112

RESUMO

INTRODUCTION: Heart valve bioprostheses are the gold standard for aortic valve surgical replacement in selected patients. OBJECTIVE: To evaluate the safety and efficacy of the National Institute of Cardiology (INC) bioprosthetic heart valve in humans. METHODS: Single-center study that included 341 patients who underwent single surgical aortic valve replacement with INC heart valve. RESULTS: 318 implants were performed de novo (93%) and 23 as redo surgery (7%); STS scores were 1.4 and 1.8%, and follow-up was for 42 and 46 months, respectively. There were no differences in clinical complications or pacemaker implantation rate. Both groups maintained a normal LVEF. Overall improvement in functional class was observed, with worsening only in two patients of the de novo group. INC prosthesis dysfunction requiring surgical reintervention was observed in eight patients (4.65%) of the de novo group vs. one patient in the redo group. CONCLUSIONS: The INC heart valve is efficacious and safe, and is associated with a low rate of complications and functional class improvement during long-term follow-up. Prospective, comparative studies of this valve are required.


INTRODUCCIÓN: Las bioprótesis de válvulas cardiacas son el estándar de oro para el reemplazo quirúrgico de la válvula aórtica en pacientes seleccionados. OBJETIVO: Evaluar la seguridad y eficacia de la válvula cardiaca bioprotésica del Instituto Nacional de Cardiología (INC) en humanos. MÉTODOS: Estudio unicéntrico que incluyó 341 pacientes que se sometieron a reemplazo valvular quirúrgico único de válvula aórtica con válvula INC. RESULTADOS: Se realizaron 318 implantes de novo (93 %) y 23 como segunda cirugía (7 %); las puntuaciones STS fueron de 1.4 y 1.8 % y el seguimiento de 42 y 46 meses, respectivamente. No existieron diferencias en las complicaciones ni en la tasa de implantación de marcapasos. Ambos grupos mantuvieron una FEVI normal. Se observó mejoría global en la clase funcional con empeoramiento solo en dos pacientes del grupo de novo. La disfunción de la prótesis INC que ameritó reintervención quirúrgica se observó en ocho pacientes (4.65 %) del grupo de novo versus un paciente (7.69 %) con segunda cirugía. CONCLUSIONES: La válvula cardiaca INC es eficaz y segura, se asocia a baja tasa de complicaciones y mejoría de la clase funcional durante el seguimiento a largo plazo. Se necesitan estudios prospectivos comparativos de esta válvula.


Assuntos
Estenose da Valva Aórtica , Cardiologia , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Humanos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Estudos Prospectivos , Valva Aórtica/cirurgia , Falha de Prótese , Resultado do Tratamento , Estenose da Valva Aórtica/cirurgia , Reoperação
4.
Int J Environ Health Res ; 31(7): 872-888, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31835907

RESUMO

Dengue is a major public health concern mainly in tropical and subtropical environments worldwide. Despite several attempts to prevent this disease occurring in tropical regions of Mexico, it has not yet been controlled. This work focused on spatial modeling of confirmed dengue fever cases that occurred during the period 2010-2014 in the Huasteca Potosina region of Mexico. Multivariable Logistic Regression Modeling (MLRM) was used to determine the relationship between explanatory variables and the presence/absence of dengue. Model performance was evaluated using the area under curve (AUC) of the relative operating characteristic (ROC); AUC > 0.95. A high spatial resolution map was created to reveal the most probable patterns of dengue risk. Our results can be used for targeted control and prevention programs at local and regional levels. This methodology can be applied to other major diseases that are spatially distributed in accordance with environmental factors.


Assuntos
Dengue/epidemiologia , Modelos Logísticos , Altitude , Humanos , Incidência , México/epidemiologia , Densidade Demográfica , Risco , Tempo (Meteorologia)
5.
Exp Eye Res ; 191: 107920, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31923415

RESUMO

A major risk for the development of primary open-angle glaucoma (POAG) is elevated intraocular pressure (IOP). Elevated IOP is caused by increased outflow resistance due in part to excessive extracellular matrix (ECM) deposition in the trabecular meshwork (TM). The role of transforming growth factor beta 2 (TGFß2) in inducing ECM production is well understood. Recent studies suggest that toll-like receptor 4 (TLR4) plays an important role in fibrogenesis. We have previously described a crosstalk between TGFß2 and TLR4 in the development of ocular hypertension and glaucomatous TM damage. Nuclear factor-kappa beta (NF-κB) is critical for TLR4 signaling. To determine the transactivation of NF-κB, TM cells were stimulated with cellular fibronectin containing the EDA isoform (cFN-EDA), TGFß2, or lipopolysaccharide (LPS) in combination with a selective TLR4 inhibitor. cFN-EDA, TGFß2, and LPS all induced transactivation of NF-κB and inhibition of TLR4 blocked the effect of each treatment paradigm. To evaluate the role of NF-κB in IOP regulation, we utilized our inducible mouse model of ocular hypertension by injection of Ad5.TGFß2 in mice harboring a mutation in NF-κB and wild-type controls. IOP was measured over time and eyes accessed by immunohistochemistry for the ECM protein FN and the specific FN-EDA isoform. Ad5.TGFß2 induced ocular hypertension and expression of FN and FN-EDA in wild-type mice, but mutation in NF-κB blocked the effect. These data suggest that NF-κB is necessary for TGFß2-induced ECM production and ocular hypertension and the transactivation of NF-κB is dependent on both TGFß2 and TLR4.


Assuntos
NF-kappa B/fisiologia , Hipertensão Ocular/induzido quimicamente , Transdução de Sinais/fisiologia , Malha Trabecular/efeitos dos fármacos , Fator de Crescimento Transformador beta2/farmacologia , Adenoviridae/genética , Animais , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/metabolismo , Fibronectinas/farmacologia , Vetores Genéticos , Pressão Intraocular/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Hipertensão Ocular/metabolismo , Hipertensão Ocular/patologia , Receptor 4 Toll-Like/metabolismo , Tonometria Ocular , Malha Trabecular/metabolismo , Malha Trabecular/patologia
6.
Int J Mol Sci ; 21(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255287

RESUMO

Dry eye disease (DED), one of the most prevalent conditions among the elderly, is a chronic inflammatory disorder that disrupts tear film stability and causes ocular surface damage. Aged C57BL/6J mice spontaneously develop DED. Rapamycin is a potent immunosuppressant that prolongs the lifespan of several species. Here, we compared the effects of daily instillation of eyedrops containing rapamycin or empty micelles for three months on the aged mice. Tear cytokine/chemokine profile showed a pronounced increase in vascular endothelial cell growth factor-A (VEGF-A) and a trend towards decreased concentration of Interferon gamma (IFN)-γ in rapamycin-treated groups. A significant decrease in inflammatory markers in the lacrimal gland was also evident (IFN-γ, IL-12, CIITA and Ctss); this was accompanied by slightly diminished Unc-51 Like Autophagy Activating Kinase 1 (ULK1) transcripts. In the lacrimal gland and draining lymph nodes, we also observed a significant increase in the CD45+CD4+Foxp3+ cells in the rapamycin-treated mice. More importantly, rapamycin eyedrops increased conjunctival goblet cell density and area compared to the empty micelles. Taken together, evidence from these studies indicates that topical rapamycin has therapeutic efficacy for age-associated ocular surface inflammation and goblet cell loss and opens the venue for new investigations on its role in the aging process of the eye.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Síndromes do Olho Seco/tratamento farmacológico , Inflamação/tratamento farmacológico , Interferon gama/genética , Fator A de Crescimento do Endotélio Vascular/genética , Envelhecimento/efeitos dos fármacos , Animais , Antígenos CD4/genética , Linhagem da Célula/efeitos dos fármacos , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/patologia , Córnea , Modelos Animais de Doenças , Síndromes do Olho Seco/genética , Síndromes do Olho Seco/patologia , Fatores de Transcrição Forkhead/genética , Células Caliciformes/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/patologia , Antígenos Comuns de Leucócito/genética , Camundongos , Soluções Oftálmicas/farmacologia , Sirolimo/farmacologia , Lágrimas/efeitos dos fármacos , Lágrimas/metabolismo
7.
J Autoimmun ; 93: 45-56, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29934134

RESUMO

CD25 knock-out (CD25KO) mice spontaneously develop Sjögren Syndrome (SS)-like inflammation. We investigated the role of commensal bacteria by comparing CD25KO mice housed in conventional or germ-free conditions. Germ-free CD25KO mice have greater corneal barrier dysfunction, lower goblet cell density, increased total lymphocytic infiltration score, increased expression of IFN-γ, IL-12 and higher a frequency of CD4+IFN-γ+ cells than conventional mice. CD4+ T cells isolated from female germ-free CD25KO mice adoptively transferred to naive immunodeficient RAG1KO recipients caused more severe Sjögren-like disease than CD4+ T cells transferred from conventional CD25KO mice. Fecal transplant in germ-free CD25KO mice reversed the spontaneous dry eye phenotype and decreased the generation of pathogenic CD4+IFN-γ+ cells. Our studies indicate that lack of commensal bacteria accelerates the onset and severity of dacryoadenitis and generates autoreactive CD4+T cells with greater pathogenicity in the CD25KO model, suggesting that the commensal bacteria or their metabolites products have immunoregulatory properties that protect exocrine glands in the CD25KO SS model.


Assuntos
Córnea/imunologia , Dacriocistite/microbiologia , Proteínas de Homeodomínio/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Aparelho Lacrimal/imunologia , Síndrome de Sjogren/microbiologia , Simbiose/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Córnea/patologia , Dacriocistite/genética , Dacriocistite/imunologia , Dacriocistite/patologia , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Feminino , Microbioma Gastrointestinal/imunologia , Regulação da Expressão Gênica , Vida Livre de Germes , Células Caliciformes/imunologia , Células Caliciformes/patologia , Proteínas de Homeodomínio/genética , Interferon gama/genética , Interferon gama/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Subunidade alfa de Receptor de Interleucina-2/deficiência , Subunidade alfa de Receptor de Interleucina-2/genética , Aparelho Lacrimal/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Permeabilidade , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia
8.
N Engl J Med ; 369(8): 732-44, 2013 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-23964935

RESUMO

BACKGROUND: The eastern equine encephalitis (EEE) and Venezuelan equine encephalitis (VEE) viruses are pathogens that infect humans and horses in the Americas. Outbreaks of neurologic disease in humans and horses were reported in Panama from May through early August 2010. METHODS: We performed antibody assays and tests to detect viral RNA and isolate the viruses in serum samples from hospitalized patients. Additional cases were identified with enhanced surveillance. RESULTS: A total of 19 patients were hospitalized for encephalitis. Among them, 7 had confirmed EEE, 3 had VEE, and 1 was infected with both viruses; 3 patients died, 1 of whom had confirmed VEE. The clinical findings for patients with EEE included brain lesions, seizures that evolved to status epilepticus, and neurologic sequelae. An additional 99 suspected or probable cases of alphavirus infection were detected during active surveillance. In total, 13 cases were confirmed as EEE, along with 11 cases of VEE and 1 case of dual infection. A total of 50 cases in horses were confirmed as EEE and 8 as VEE; mixed etiologic factors were associated with 11 cases in horses. Phylogenetic analyses of isolates from 2 cases of equine infection with the EEE virus and 1 case of human infection with the VEE virus indicated that the viruses were of enzootic lineages previously identified in Panama rather than new introductions. CONCLUSIONS: Cases of EEE in humans in Latin America may be the result of ecologic changes that increased human contact with enzootic transmission cycles, genetic changes in EEE viral strains that resulted in increased human virulence, or an altered host range. (Funded by the National Institutes of Health and the Secretaría Nacional de Ciencia, Tecnología e Innovación, Panama.).


Assuntos
Surtos de Doenças , Vírus da Encefalite Equina do Leste , Vírus da Encefalite Equina Venezuelana , Encefalomielite Equina do Leste , Encefalomielite Equina Venezuelana , Adolescente , Animais , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Vírus da Encefalite Equina do Leste/genética , Vírus da Encefalite Equina do Leste/imunologia , Vírus da Encefalite Equina do Leste/isolamento & purificação , Vírus da Encefalite Equina Venezuelana/genética , Vírus da Encefalite Equina Venezuelana/imunologia , Vírus da Encefalite Equina Venezuelana/isolamento & purificação , Encefalomielite Equina do Leste/epidemiologia , Encefalomielite Equina do Leste/veterinária , Encefalomielite Equina Venezuelana/epidemiologia , Encefalomielite Equina Venezuelana/veterinária , Evolução Fatal , Feminino , Doenças dos Cavalos/epidemiologia , Cavalos , Humanos , Lactente , Masculino , Panamá/epidemiologia , Filogenia , RNA Viral/sangue
9.
J Infect Dis ; 212 Suppl 2: S410-3, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25999057

RESUMO

As of 25 March 2015, the largest recorded outbreak of Ebola virus infection is ongoing, with almost 25 000 cases and >10 000 deaths. There are 5 genetically and antigenically distinct species within the genus Ebolavirus. Limited cross-reactivity and protection is observed between these 5 Ebolavirus species, which complicates vaccine development. However, on the basis of sequence homology between the 5 Ebolavirus species, we hypothesize that conserved epitopes are present on the viral glycoprotein (GP), which can be targeted by antibodies. In the current study, a panel of mouse monoclonal antibodies was isolated and characterized using an enzyme-linked immunosorbent assay (ELISA) to determine cross-reactivity, avidity, and competition for epitope binding; Western blot analysis was also performed. Four monoclonal antibodies were identified by ELISA as cross-reacting with the GPs of all 5 Ebolavirus species. The identification of cross-reactive antibodies that bind the GPs of all known Ebolavirus species will give us important insight into the presence of conserved epitopes on the viral GP. These data will be crucial for the development of novel therapeutics and diagnostic assays.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Reações Cruzadas/imunologia , Ebolavirus/imunologia , Animais , Antígenos Virais/imunologia , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática/métodos , Epitopos/imunologia , Glicoproteínas/imunologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Hibridomas/imunologia , Hibridomas/virologia , Camundongos , Proteínas Virais/imunologia
10.
Emerg Infect Dis ; 21(6)2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25988479

RESUMO

Panama remains free of zoonotic tuberculosis caused by Mycobacterium bovis. However, DNA fingerprinting of 7 M. bovis isolates from a 2013 bovine tuberculosis outbreak indicated minimal homology with strains previously circulating in Panama. M. bovis dispersion into Panama highlights the need for enhanced genotype testing to track zoonotic infections.


Assuntos
Mycobacterium bovis/classificação , Tuberculose Bovina/epidemiologia , Animais , Bovinos , Genótipo , História do Século XXI , Repetições Minissatélites , Tipagem Molecular , Mycobacterium bovis/genética , Panamá/epidemiologia , Filogenia , Polimorfismo Genético , Tuberculose Bovina/história
11.
Rev Biol Trop ; 61(2): 897-925, 2013 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-23885599

RESUMO

The Sierra Madre Oriental region in the mexican state of San Luis Potosi is a relevant place for bird conservation at a country level. Therefore the main goal of this study was to analyze the geographic patterns of distribution and the conservation current state of the birds, to support the needs to expand the conservation areas in the future. Data was collected from various databases of zoological museums and collections, and field sampling methods conducted from January 2009 to May 2011. Potential distributions were modeled for 284 species using GARP software and then a map was developed to determine areas with favorable environmental characteristics for the distribution of species richness. Finally, the importance of conservation areas for the potential distribution of birds in the region was evaluated. A total of 359 species were recorded of which 71.4% are permanent residents, 19% are winter migrants and 4% are summer residents. From this total, 41 species were endemic, 47 were species at risk and 149 were neotropical migrants. The largest species richness correspond to oak forests, cloud forests, and tropical moist forests located at altitudes from 100m to 1 500m. Their potential distribution was concentrated towards the center and Southeast of the study area. Only 10% of areas with a high potential conservation was included in areas of priority for bird conservation (AICA) and just 3% of all potential areas were under some governmental category of protection. However, no conservation area has a management plan currently applied and monitored. The information generated is important for the development of management proposals for birds conservation in the region.


Assuntos
Biodiversidade , Aves/classificação , Conservação dos Recursos Naturais , Animais , México , Densidade Demográfica , Dinâmica Populacional , Estações do Ano
12.
Indian J Otolaryngol Head Neck Surg ; 75(4): 4216-4222, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37974813

RESUMO

OBJECTIVE: Carotid resection for head and neck cancer is rare, and serious complications may arise since such cancer is frequently detected in advanced stages. The objective is to describe nine cases of carotid artery resection and reconstruction due to tumor invasion. METHODS: The clinical records of nine patients who underwent carotid resection and reconstruction at our hospital were retrospectively reviewed. Carotid body tumors were evaluated with the aid of a vascular team in case carotid resection was necessary at the time of surgery. CT angiography to determine the status of the circle of Willis was performed in all patients who might undergo carotid resection and reconstruction in case of failure to restore cerebral blood flow and thus reduce possible sequelae due to ligation. RESULTS: Of nine patients, 6 had carotid body tumors, 1 had a thyroid tumor of conglomerate lymph nodes, 1 had a larynx tumor of conglomerate lymph nodes, and 1 had a myofibroblastic tumor. There were no intraoperative cerebrovascular accidents. One patient (11.1%) had a cerebrovascular accident secondary to carotid hematoma in the intermediate postoperative period that required vascular graft removal. One patient (11.1%) died seven days after surgery following an ischemic cerebrovascular accident. Eight patients remain asymptomatic, and 1 patient with recurrence and metastasis. CONCLUSIONS: Carotid resection remains a controversial issue in the treatment of advanced head and neck cancer. However, carotid resection and reconstruction are required for disease control, and complications such as thrombosis or vascular accidents may arise. Fortunately, this is a rare condition. We recommend carotid reconstruction for all patients in whom resection is required for tumor control. Ligation should be a last resort, as seen in the management of one of our patients.

13.
Front Cell Dev Biol ; 10: 936115, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912101

RESUMO

Primary open-angle glaucoma is one of the leading causes of blindness worldwide. With limited therapeutics targeting the pathogenesis at the trabecular meshwork (TM), there is a great need for identifying potential new targets. Recent evidence has implicated Toll-like receptor 4 (TLR4) and it is signaling pathway in augmenting the effects of transforming growth factor beta-2 (TGFß2) and downstream extracellular matrix production. In this review, we examine the role of TLR4 signaling in the trabecular meshwork and the interplay between endogenous activators of TLR4 (damage-associated molecular patterns (DAMPs)), extracellular matrix (ECM), and the effect on intraocular pressure.

14.
Sci Rep ; 12(1): 4512, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35296712

RESUMO

Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface. One such molecule is butyrate, a short-chain fatty acid (SCFA) produced by certain members of the gut microbiota through fermentation of dietary fiber. Here we show that SCFA transporter SLC5A8 is expressed in vivo in murine conjunctival and corneal epithelium. Pre-treatment of in vitro corneal epithelial cultures or bone marrow-derived dendritic cells (BMDCs) with phenylbutyrate (PBA) reduces lipopolysaccharide-induced pro-inflammatory Tnf expression. Corneal epithelial cultures and BMDCs isolated from Slc5a8 knockout mice are unable to respond to PBA pre-treatment, suggesting that SLC5A8 is required for the protective effect of PBA. The treatment of mice undergoing desiccating stress (DS) with oral tributyrin, a prodrug form of butyrate, reduces inflammation at the ocular surface in vivo, and this effect partially requires SLC5A8. Finally, expression analysis on conjunctival tissue isolated from mice subjected to DS with and without tributyrin treatment revealed that treatment downregulated genes involved in Type I interferon signaling. Together these data support our hypothesis that SCFAs produced in the gut participate in the maintenance of ocular surface homeostasis.


Assuntos
Butiratos , Microbioma Gastrointestinal , Animais , Butiratos/metabolismo , Butiratos/farmacologia , Ácidos Graxos Voláteis/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Transportadores de Ácidos Monocarboxílicos/metabolismo , Lágrimas/metabolismo
15.
Geroscience ; 44(4): 2105-2128, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35279788

RESUMO

Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. Here, we aimed to characterize the immune phenotype of aged CD4+ T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4+CD25+GITR+) and non-Tregs (CD4+CD25negGITRneg) in lymphoid organs from female C57BL/6J mice and subjected these cells to an immunology NanoString® panel. These results were confirmed by flow cytometry, live imaging, and tissue immunostaining in the lacrimal gland. Importantly, effector T helper 1 (Th1) genes were highly upregulated on aged Tregs, including the master regulator Tbx21. Among the non-Tregs, we also found a significant increase in the levels of EOMESmed/high, TbetnegIFN-γ+, and CD62L+CD44negCD4+ T cells with aging, which are associated with cell exhaustion, immunopathology, and the generation of tertiary lymphoid tissue. At the functional level, aged Tregs from lymphoid organs are less able to decrease proliferation and IFN-γ production of T responders at any age. More importantly, human lacrimal glands (age range 55-81 years) also showed the presence of CD4+Foxp3+ cells. Further studies are needed to propose potential molecular targets to avoid immune-mediated lacrimal gland dysfunction with aging.


Assuntos
Aparelho Lacrimal , Tecido Linfoide , Linfócitos T Reguladores , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Camundongos , Interferon gama , Aparelho Lacrimal/citologia , Camundongos Endogâmicos C57BL , Fenótipo , Pessoa de Meia-Idade , Tecido Linfoide/citologia
16.
J Thorac Dis ; 14(6): 1815-1829, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35813724

RESUMO

Background: Aortic diseases in some orphan rheumatological diseases require medical, surgical or peripheral endovascular intervention because they can be catastrophic. Objectives: to analyze the main clinical and epidemiological characteristics of patients with Takayasu arteritis (TA), Marfan syndrome (MS) and similar conditions that were treated with cardiothoracic surgery and peripheral endovascular intervention. Methods: Retrospective and descriptive cohort study that included patients of any age and gender with TA (as per the criteria of the American College of Rheumatology and EULAR/PRINTO), MS (according to Ghent criteria), and similar conditions who underwent cardiothoracic surgery or peripheral endovascular intervention. Data were collected from electronic charts. Results: A total of 77 patients with TA and 135 patients with MS and similar conditions were included. The frequency of surgical or interventional requirements in patients with TA and MS/similar conditions was 77/364 (21.2%) and 135/300 (45%), respectively; such patients were followed for a median of 6 [2-12] and 3.29 (0.42-6.62) years, with (maximum follow-up range of 47 and 21.37 years, respectively). Aneurysms were present in 11 (14.3%) and 66 (48.9%) in patients with TA and MS/similar conditions, respectively. Aortic, mitral and tricuspid valve damage occurred in 8 (10.4%) patients, 4 (5.2%) patients and 1 (1.3%) patient with TA, respectively; corresponding frequencies in patients with MS/similar conditions were 98 (72.6%), 50 (37.0%) and 20 (14.8%). We identified that 20% of patients with TA died after 5.08 years (95% CI: 0.23-25.42 years) and 20 % of the patients with MS and other similar conditions died after 7.52 years (95% CI: 1.10-9.02 years). Conclusions: The frequency of surgical intervention was low in this study. Long-term prognosis is good if surgery is performed in a timely manner. Epidemiological studies provide relevant information for public health decisions related to the management of orphan rheumatological diseases.

17.
Invest Ophthalmol Vis Sci ; 63(2): 12, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35129590

RESUMO

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings.


Assuntos
Humor Aquoso/fisiologia , Consenso , Glaucoma/metabolismo , Pressão Intraocular/fisiologia , Hipertensão Ocular/metabolismo , Malha Trabecular/metabolismo , Animais , Modelos Animais de Doenças , Glaucoma/fisiopatologia , Camundongos , Hipertensão Ocular/fisiopatologia , Tonometria Ocular
18.
Cir Cir ; 89(S1): 37-42, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34762622

RESUMO

Undescended parathyroid adenoma is a rare cause of primary hyperparathyroidism that happens < 1% of cases. If not suspected, it can lead to a negative bilateral parathyroid exploration and extensive iatrogenic trauma. We propose that with proper imaging the correct diagnosis can be established to simplify surgical management. We describe two cases of patients who underwent a targeted neck exploration due to an undescended parathyroid adenoma diagnosed with an appropriate preoperative imaging protocol. With an appropriate imaging protocol for primary hyperparathyroidism and parathyroid hormone aspirates, an undescended parathyroid adenoma can be primarily diagnosed to guide a focused parathyroidectomy.


El adenoma paratiroideo no descendido ocasiona hiperparatiroidismo primario en <1% de los casos. Si no se sospecha, puede llevar a exploraciones negativas y trauma iatrogénico extenso. Proponemos que, con un protocolo imagenológico adecuado, se puede realizar un diagnóstico correcto, simplificando el abordaje quirúrgico. Describimos dos casos en que se realizó una exploración de cuello dirigida debido a un adenoma paratiroideo no descendido diagnosticado con un protocolo de imagen preoperatorio apropiado. Un protocolo de imagen apropiado para hiperparatiroidismo primario y aspirados de PTH pueden diagnosticar de manera inicial un adenoma paratiroideo no descendido para guiar una paratiroidectomía dirigida.


Assuntos
Adenoma , Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Adenoma/complicações , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Humanos , Hiperparatireoidismo Primário/etiologia , Hiperparatireoidismo Primário/cirurgia , Glândulas Paratireoides , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia
19.
Mucosal Immunol ; 12(4): 897-908, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30696983

RESUMO

Aging is a significant risk factor for dry eye. Here we used a murine aging model to investigate the effects of aging on antigen presenting cells (APCs) and generation of pathogenic T helper (Th)-1 cells. Our results showed that APCs from aged mice accumulate at the conjunctiva, have higher levels of co-activation marker CD86 and lower aldehyde dehydrogenase activity. Using topical ovalbumin peptide as a surrogate antigen, we observed an increased number of antigen-loaded APCs in the draining cervical lymph nodes in the aged group and loss of tight junction protein occludin in the conjunctiva. Aged cervical lymph nodes APCs showed a greater generation of Th1 cells than young APCs in antigen-presentation assays in vitro. Aged lacrimal glands, and draining nodes showed an accumulation of IFN-γ producing CD4+T cells, while Th-17 cells were present only in aged draining nodes. There was also an age-related increase in CD4+CXCR3+IFN-γ+ cells in the conjunctiva, nodes, and lacrimal glands while CD4+CCR6+IL-17A+ cells increased in the draining nodes of aged mice. Adoptive transfer of aged CD4+CXCR3+ cells into young, naive immunodeficient recipients caused greater goblet cell loss than young CD4+CXCR3+ donor cells. Our results demonstrate that age-associated changes in APCs are critical for the pathogenesis of age-related dry eye.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Síndromes do Olho Seco/etiologia , Células Th1/imunologia , Transferência Adotiva , Envelhecimento/genética , Envelhecimento/imunologia , Envelhecimento/metabolismo , Animais , Células Apresentadoras de Antígenos/metabolismo , Biomarcadores , Senescência Celular/genética , Senescência Celular/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/fisiopatologia , Síndromes do Olho Seco/terapia , Feminino , Ativação Linfocitária , Camundongos , Camundongos Knockout , Células Th1/metabolismo
20.
Ambio ; 37(5): 381-9, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18828284

RESUMO

This article analyzes the relationship between the configuration and spatial reorganization of land-use and land-cover in the Pujal-Coy project area, Huasteca Potosina region, eastern San Luis Potosí, Mexico, as well as the relationship between these changes and the environmental conditions prevailing in the area. Land-use and land-cover changes were determined through the analysis and interpretation of satellite images from different dates. The changes identified in the different study periods were correlated with the prevailing physical factors. The results show that the spatial configuration of farming activities, initially induced by the implementation of a regional development project, is highly correlated to the presence of limiting factors such as soil type, slope, and climate. Particularly, the former represents the element that has led to the establishment of the current distribution pattern of farming activities.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental/métodos , Agricultura , Clima , Sistemas de Informação Geográfica , Geografia , México , Solo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA