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Medicinas Complementárias
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1.
J Dermatol Sci ; 99(1): 17-22, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32518053

RESUMEN

BACKGROUND: Diagnosis of pyoderma gangrenosum, acne and hidradenitis suppurativa (PASH) and pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) patients, in spite of recently identified genetic variations, is just clinical, since most patients do not share the same mutations, and the mutations themselves are not informative of the biological pathways commonly disrupted in these patients. OBJECTIVE: To reveal genetic changes more closely related to PASH and PAPASH etiopathogenesis, identifying novel common pathways involved in these diseases. METHODS: Cohort study on PASH (n = 4) and PAPASH (n = 1) patients conducted using whole exome sequencing (WES) approach and a novel bioinformatic pipeline aimed at discovering potentially candidate genes selected from density mutations and involved in pathways relevant to the disease. RESULTS: WES results showed that patients presented 90 genes carrying mutations with deleterious and/or damage impact: 12 genes were in common among the 5 patients and bared 237 ns ExonVar (54 and 183 in homozygosis and heterozygosis, respectively). In the pathway enrichment analysis, only 10 genes were included, allowing us to retrieve 4 pathways shared by all patients: (1) Vitamin D metabolism, (2) keratinization, (3) formation of the cornified envelope and (4) steroid metabolism. Interestingly, all patients had vitamin D levels lower than normal, with a mean value of 10 ng/mL. CONCLUSION: Our findings, through a novel strategy for analysing the genetic background of syndromic HS patients, suggested that vitamin D metabolism dysfunctions seem to be crucial in PASH and PAPASH pathogenesis. Based on low vitamin D serum levels, its supplementation is envisaged.


Asunto(s)
Acné Vulgar/diagnóstico , Artritis Infecciosa/diagnóstico , Secuenciación del Exoma , Hidradenitis Supurativa/diagnóstico , Piodermia Gangrenosa/diagnóstico , Piel/patología , Vitamina D/metabolismo , Acné Vulgar/genética , Acné Vulgar/metabolismo , Acné Vulgar/patología , Adolescente , Adulto , Artritis Infecciosa/genética , Artritis Infecciosa/metabolismo , Artritis Infecciosa/patología , Biología Computacional , Femenino , Estudios de Seguimiento , Hidradenitis Supurativa/genética , Hidradenitis Supurativa/metabolismo , Hidradenitis Supurativa/patología , Humanos , Queratinocitos/patología , Masculino , Piodermia Gangrenosa/genética , Piodermia Gangrenosa/metabolismo , Piodermia Gangrenosa/patología , Piel/citología , Síndrome , Adulto Joven
2.
Vet Immunol Immunopathol ; 160(3-4): 158-66, 2014 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-24856731

RESUMEN

The major forms of inflammatory canine arthritis are immune-mediated arthritis (IMA) and septic arthritis (SA), although some cases of cruciate disease (CD) are associated with significant levels of synovitis. In this study, the bacteria associated with canine arthritis were identified and mRNA expression levels of Toll-like receptors (TLRs) and pro-inflammatory cytokines determined. Of the 40 synovial fluid samples analysed, bacteria were isolated from 12 samples by culture (2 CD, 10 SA) and detected in 4 samples (3 CD, 1 SA) using culture-independent methods. Statistically significant increases in TLR2, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-12 mRNA expression were seen in all disease groups compared to normal controls. All disease groups had decreased mRNA expression of other TLRs compared to normal controls, but this did not reach statistical significance. Synovial fluid cell counts revealed that the highest number and proportion of mononuclear cells and neutrophils were found in the IMA and SA samples, respectively. Age had an effect on the TLR and cytokine mRNA expression profiles: TNF-α (p=0.043) and IL-12 (p=0.025) mRNA expression was increased and TLR4 mRNA expression was reduced (p=0.033) in dogs up to 4 years of age compared to older animals. In the 10 SA samples from which bacteria were isolated, statistically significant increases in TLR2, TLR7, TNF-α and IL-6 mRNA expression were observed. It is concluded that canine arthritis is associated with increased mRNA levels of pro-inflammatory cytokines, which could in some cases be mediated by bacteria through activation of TLR2.


Asunto(s)
Artritis Infecciosa/veterinaria , Artritis/veterinaria , Citocinas/genética , Enfermedades de los Perros/genética , Enfermedades de los Perros/microbiología , Receptores Toll-Like/genética , Envejecimiento/genética , Envejecimiento/inmunología , Animales , Artritis/genética , Artritis/microbiología , Artritis Infecciosa/genética , Artritis Infecciosa/microbiología , Bacterias/genética , Bacterias/aislamiento & purificación , Enfermedades de los Perros/inmunología , Perros , Genes Bacterianos , Genes de ARNr , Mediadores de Inflamación/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Líquido Sinovial/inmunología , Líquido Sinovial/microbiología , Sinovitis/genética , Sinovitis/microbiología , Sinovitis/veterinaria , Transcriptoma
3.
J Invest Dermatol ; 134(7): 1805-1810, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24599175

RESUMEN

During the past years, significant progress in the understanding of the complexity, regulation, and relevance of innate immune responses underlying several inflammatory conditions with neutrophilic skin involvement has been made. These diseases belong to the novel class of autoinflammatory diseases, and several are caused by mutations in genes regulating the function of innate immune complexes, termed inflammasomes, leading to enhanced secretion of the proinflammatory cytokine IL-1ß. Consequently, targeting of IL-1ß has proven successful in the treatment of these diseases, and the identification of related pathogenic mechanisms in other more common skin diseases characterized by autoinflammation and neutrophilic tissue damage also provides extended opportunities for therapy by interfering with IL-1 signaling.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Terapia Biológica , Inflamasomas/inmunología , Queratinocitos/inmunología , Enfermedades de la Piel/inmunología , Acné Vulgar/genética , Acné Vulgar/inmunología , Acné Vulgar/terapia , Síndrome de Hiperostosis Adquirido/genética , Síndrome de Hiperostosis Adquirido/inmunología , Síndrome de Hiperostosis Adquirido/terapia , Animales , Artritis Infecciosa/genética , Artritis Infecciosa/inmunología , Artritis Infecciosa/terapia , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/terapia , Humanos , Inflamasomas/genética , Ratones , Piodermia Gangrenosa/genética , Piodermia Gangrenosa/inmunología , Piodermia Gangrenosa/terapia , Síndrome de Schnitzler/genética , Síndrome de Schnitzler/inmunología , Síndrome de Schnitzler/terapia , Enfermedades de la Piel/genética , Enfermedades de la Piel/terapia
4.
J Immunol ; 168(8): 3950-7, 2002 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-11937551

RESUMEN

Lactoferrin (Lf) is an iron-binding protein of external secretions and neutrophil secondary granules with antimicrobial and immunomodulatory activities. To further define these properties of Lf, we have investigated the response to Staphylococcus aureus infection in transgenic mice carrying a functional human Lf gene. The transgenic mice cleared bacteria significantly better than congenic littermates, associated with a trend to reduced incidence of arthritis, septicemia, and mortality. We identified two pathways by which S. aureus clearance was enhanced. First, human Lf directly inhibited the growth of S. aureus LS-1 in vitro. Second, S. aureus-infected transgenic mice exhibited enhanced Th1 immune polarization. Thus, spleen cells from infected transgenic mice produced higher levels of TNF-alpha and IFN-gamma and less IL-5 and IL-10 upon stimulation ex vivo with the exotoxin toxic shock syndrome toxin-1 compared with congenic controls. To confirm that these effects of Lf transgene expression could occur in the absence of live bacterial infection, we also showed that Lf-transgenic DBA/1 mice exhibited enhanced severity of collagen-induced arthritis, an established model of Th1-induced articular inflammation. Higher levels of stainable iron in the spleens of transgenic mice correlated with human Lf distribution, but all other parameters of iron metabolism did not differ between transgenic mice and wild-type littermates. These results demonstrate that human Lf can mediate both antimicrobial and immunomodulatory activities with downstream effects on the outcome of immune pathology in infectious and inflammatory disease.


Asunto(s)
Adyuvantes Inmunológicos/genética , Lactoferrina/genética , Ratones Transgénicos/inmunología , Infecciones Estafilocócicas/genética , Infecciones Estafilocócicas/inmunología , Células TH1/inmunología , Células TH1/microbiología , Adyuvantes Inmunológicos/biosíntesis , Adyuvantes Inmunológicos/fisiología , Adyuvantes Inmunológicos/uso terapéutico , Animales , Artritis Experimental/genética , Artritis Experimental/inmunología , Artritis Experimental/microbiología , Artritis Infecciosa/genética , Artritis Infecciosa/inmunología , Artritis Infecciosa/microbiología , Citocinas/biosíntesis , Citocinas/sangre , Humanos , Hierro/metabolismo , Lactoferrina/biosíntesis , Lactoferrina/fisiología , Lactoferrina/uso terapéutico , Hígado/metabolismo , Activación de Linfocitos/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Endogámicos DBA , Bazo/citología , Bazo/inmunología , Bazo/metabolismo , Bazo/patología , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/inmunología , Células TH1/metabolismo
5.
Microb Pathog ; 26(1): 35-43, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9973579

RESUMEN

Genetic background is important in determining whether certain infecting bacteria disseminate to the joint and cause arthritis. We assessed whether APOE genotype is associated with the presence of DNA from Chlamydia or other bacteria in synovial tissues of patients with various arthritides. Nucleic acids from synovial tissues of 135 patients were screened by PCR for DNA from Chlamydia trachomatis, C. pneumoniae and other bacteria (pan-bacteria). APOE genotype was determined by a PCR-based method for all patients in each of four resulting groups comprised of about 35 individuals each, positive for C. trachomatis only, C. pneumoniae only, other bacteria, or no bacteria. RT-PCR was used to assess synovial APOE expression. The latter assays confirmed that APOE mRNA is present in synovial tissue. Determination of APOE genotype showed that patients PCR-negative in all assays, and those positive in the C. trachomatis - and pan-bacteria- (excluding Chlamydia) directed assays, had distributions of the APOE epsilon2, epsilon3 and epsilon4 alleles mirroring those of the general population (i.e. about 8%, 79% and 13%, respectively). In contrast, 68% of patients with C. pneumoniae DNA in synovium possessed a copy of the epsilon4 allele. These results indicate that no association exists between APOE genotype and synovial presence of C. trachomatis or other bacteria. However, individuals bearing at least one copy of the APOE epsilon4 allele may be at increased risk for synovial infection by C. pneumoniae.


Asunto(s)
Apolipoproteínas E/genética , Artritis Infecciosa/genética , Artritis/genética , Infecciones por Chlamydia/genética , Chlamydia/aislamiento & purificación , Líquido Sinovial/microbiología , Alelos , Artritis/microbiología , Artritis Infecciosa/microbiología , Bacterias/genética , Bacterias/aislamiento & purificación , Chlamydia/genética , Infecciones por Chlamydia/microbiología , Chlamydia trachomatis/genética , Chlamydia trachomatis/aislamiento & purificación , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/aislamiento & purificación , Humanos , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
6.
Microbes Infect ; 1(10): 745-51, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10816079

RESUMEN

The integrin-associated protein (IAP) has been shown to function in a signaling complex with beta3 integrins, influencing the migration of phagocytic cells into inflamed tissues. We have previously shown that gene-targeted mice deficient for IAP succumbed to peritonitis when inoculated with gram-negative bacteria. The aim of this study was to assess the role of IAP in our recently established model of haematogenously induced Staphylococcus aureus septicaemia and arthritis. In this model, neutrophils play a crucial role in the early phase of the infection. Mice lacking IAP and congenic controls were intravenously inoculated with S. aureus LS-1. The IAP-/- mice were resistant to developing clinical signs of arthritis compared with their IAP-expressing littermates. The clinical findings were corroborated by histopathological evaluation indicating that the IAP-/- mice had less cartilage and bone destruction in the joints. We believe that a delayed migration of leukocytes into the joints of mice lacking IAP expression leads to decreased susceptibility to develop S. aureus-induced arthritis.


Asunto(s)
Antígenos CD/inmunología , Artritis Infecciosa/inmunología , Proteínas Portadoras/inmunología , Infecciones Estafilocócicas/inmunología , Staphylococcus aureus/inmunología , Animales , Antígenos CD/genética , Artritis Infecciosa/genética , Artritis Infecciosa/microbiología , Antígeno CD47 , Proteínas Portadoras/genética , Inhibición de Migración Celular , Femenino , Fibronectinas/metabolismo , Fibronectinas/farmacología , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Aceite de Oliva , Fagocitosis/inmunología , Aceites de Plantas/farmacología , Unión Proteica , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/metabolismo , Vitronectina/metabolismo , Vitronectina/farmacología
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