RESUMEN
OBJECTIVE: Lumican (LUM) is a major extracellular matrix glycoprotein in adult articular cartilage and its expression is known to be upregulated upon cartilage degeneration. LUM is associated with the pathogen-associated molecular pattern (PAMP) activation of the TLR4 signalling cascade, with TLR4 being highly associated with inflammation in rheumatic diseases. However, the main role of the LUM structural molecule in osteoarthritis (OA) remains elusive. The aim of this study was, therefore, to understand the role of LUM during TLR4-mediated activation in OA. METHODS: After measuring LUM levels in synovial fluid (SF) of OA patients and lipopolysaccharide (LPS)-induced TLR4 activation, the role of LUM in the expression of pro-inflammatory molecules and cartilage degradation was assessed in vitro and ex vivo in a cartilage explant model. Primary macrophage activation and polarization were studied upon LUM co-stimulation with LPS. RESULTS: We demonstrate that LUM is not only significantly upregulated in SF from OA patients compared to healthy controls, but also that LUM increases lipopolysaccharide (LPS)-induced TLR4 activation. Furthermore, we show that a pathophysiological level of LUM augments the LPS-induced TLR4 activation and expression of downstream pro-inflammatory molecules, resulting in extensive cartilage degradation. LUM co-stimulation with LPS also provided a pro-inflammatory stimulus, upregulating primary macrophage activation and polarization towards the M1-like phenotype. CONCLUSIONS: These findings strongly support the role of LUM as a mediator of PAMP-induced TLR4 activation of inflammation, cartilage degradation, and macrophage polarization in the OA joint and potentially other rheumatic diseases.
Asunto(s)
Cartílago/metabolismo , Lumican/fisiología , Macrófagos/fisiología , Osteoartritis/metabolismo , Receptor Toll-Like 4/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Diferenciación Celular , Condrocitos/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Lumican/análisis , Lumican/metabolismo , Activación de Macrófagos , Masculino , Persona de Mediana Edad , FN-kappa B/metabolismo , Líquido Sinovial/química , Líquido Sinovial/metabolismo , Receptor Toll-Like 4/metabolismo , Regulación hacia ArribaRESUMEN
OBJECTIVE: The basic aim of this study is to compare the pregnancy outcomes in cases with uterine fibroids located at the anterior and posterior uterine walls. MATERIALS AND METHODS: A total of 84 pregnant women with a diagnosis of uterine myoma larger than 30 millimeter (mm) in diameter were included in the study to determine the obstetric outcomes. In 64 (76.20%) patients, myomas were detected at the anterior uterine wall (group 1), while 20 (23.80%) were detected at the posterior uterine wall (group 2). All patients were followed monthly until the end of pregnancy. Demographic and obstetric characteristics were compared between the two groups. RESULTS: There were no significant differences in age, gravida, parity, and myoma size between the two groups. A significant difference existed between the groups with regard to pelvic pain. Posterior located fibroids were associated with more pelvic pain (p = 0.001). No difference was observed between the two groups with regard to the rates of preterm delivery, bleeding in early pregnancy, infants with small for gestational age, and hospitalization period during pregnancy. Women with posterior located myomas had significantly higher miscarriage rates. CONCLUSION: Our findings suggest that pregnancies with uterine fibroids are at increased risk for complications. Posterior located fibroids larger than 30 mm in diameter are associated with severe pelvic pain compared to anterior located fibroids.
Asunto(s)
Leiomioma/patología , Complicaciones Neoplásicas del Embarazo/patología , Resultado del Embarazo , Neoplasias Uterinas/patología , Aborto Espontáneo/epidemiología , Adulto , Comorbilidad , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Leiomioma/complicaciones , Leiomioma/diagnóstico por imagen , Leiomioma/epidemiología , Dolor Pélvico/etiología , Embarazo , Complicaciones Neoplásicas del Embarazo/diagnóstico por imagen , Complicaciones Neoplásicas del Embarazo/epidemiología , Estudios Retrospectivos , Ultrasonografía Prenatal , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/epidemiologíaRESUMEN
AIM: To investigate levels of matrix metalloproteinases 2 and 9, and of their tissue inhibitor (i.e. tissue inhibitor matrix metalloproteinase 1), in the serum of patients with tympanosclerosis. MATERIALS AND METHOD: We included 40 patients (age range 13-63 years) who had undergone surgery in the ENT department of Izmir Atatürk Training and Research Hospital between 2002 and 2007. Twenty had uncomplicated chronic otitis media and 20 had tympanosclerosis. We also included as the control group 20 individuals with no history of previous otic complaints or systemic or infectious disease. Serum levels of serum matrix metalloproteinases 2 and 9 and of tissue inhibitor matrix metalloproteinase 1 were measured in all subjects and compared. RESULT: Significantly higher levels of serum matrix metalloproteinases 2 and 9 were found in the tympanosclerosis group, compared with the chronic otitis media and control groups. There was no statistically significant difference in tissue inhibitor matrix metalloproteinase 1 level between the three groups. CONCLUSION: Tympanosclerosis surgery has poor success rates, since the pathological process is still active. We suggest that high levels of matrix metalloproteinases may play a role in the continuation of the disease process.
Asunto(s)
Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Otitis Media/sangre , Inhibidor Tisular de Metaloproteinasa-1/sangre , Membrana Timpánica/patología , Adolescente , Adulto , Animales , Estudios de Casos y Controles , Enfermedad Crónica , Perros , Ensayo de Inmunoadsorción Enzimática , Femenino , Gerbillinae , Cobayas , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/fisiología , Metaloproteinasa 9 de la Matriz/fisiología , Persona de Mediana Edad , Esclerosis , Inhibidor Tisular de Metaloproteinasa-1/fisiología , Adulto JovenRESUMEN
Germ cell tumors constitute a very complicated group of tumors of the ovary and their histogenesis is not yet clarified. Besides their histological heterogeneity, sarcomatous areas have also been described. A right ovarian mass was found in a 23-year-old female, who was being treated in the hospital for miscarriage. Disseminated omental metastases were detected during abdominal laparotomy. Pathological examination of the dissected material revealed the tumor to be a mixed germ cell tumor (immature teratoma and dysgerminoma) with sarcomatous component. Areas resembling granulosa cell tumor were also encountered. This ovarian tumor with many different histopathological features is presented with a review of the literature. The importance of thorough sampling in determining the type and extent of the malignant components is also emphasized due to their direct relation with the prognosis.