RESUMEN
OBJECTIVE: To determine whether the structure of chondroitin sulfate (CS) in cartilage is reflected by the degree of cartilage degeneration in patients with osteoarthritis (OA) of the knee and to determine how CS biosynthesis affects cartilage degeneration. DESIGN: Two osteoarthritic cartilage samples were obtained from medial femoral condyle (MFC) and lateral femoral condyle (LFC) of 24 knees with end-stage OA. The samples were assigned to two groups as follows: lesion and remote cartilage were adjacent to and remote from the osteoarthritic cartilage, respectively. Histological grade was determined according to the Mankin score. The CS concentration and chain length were determined using high-performance liquid chromatography (HPLC) and gel filtration chromatography, respectively. Expression of the gene encoding CS glycosyltransferase was evaluated using a real-time quantitative polymerase chain reaction (qPCR) assay. These results were compared between lesion and remote cartilage. RESULTS: The Mankin score indicated that lesion cartilage was more degraded compared with remote cartilage. Although the CS levels varied among individuals, the mean CS concentration and chain length were significantly lower and shorter in lesion cartilage than in remote cartilage, respectively (concentration: 12.04 vs 14.84 µg/mg wet weight, P = 0.021; chain length: 5.36 vs 6.19 kDa, P = 0.026). Three genes encoding CS glycosyltransferases (CHPF, CSGALNACT1, CSGALNACT2) were expressed at lower levels in lesion cartilage. CONCLUSIONS: In the osteoarthritic knee, the CS concentration and chain length were reduced closer to the more degraded cartilage with decreasing CS glycosyltransferase gene expression. Inhibition of CS glycosyltransferase gene expression may reduce CS chain length, which may contribute to OA progression.
Asunto(s)
Cartílago Articular/metabolismo , Condrocitos/metabolismo , Sulfatos de Condroitina/metabolismo , Articulación de la Rodilla/metabolismo , Osteoartritis de la Rodilla/metabolismo , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Sulfatos de Condroitina/química , Femenino , Regulación Enzimológica de la Expresión Génica , Glicosiltransferasas/biosíntesis , Glicosiltransferasas/genética , Humanos , Deformidades Adquiridas de la Articulación/diagnóstico por imagen , Deformidades Adquiridas de la Articulación/etiología , Deformidades Adquiridas de la Articulación/metabolismo , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Peso Molecular , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/patología , ARN Mensajero/genética , RadiografíaRESUMEN
A delay in establishing the diagnosis of an occult fracture of the hip that remains unrecognised after plain radiography can result in more complex treatment such as an arthroplasty being required. This might be avoided by earlier diagnosis using MRI. The aim of this study was to investigate the best MR imaging sequence for diagnosing such fractures. From a consecutive cohort of 771 patients admitted between 2003 and 2011 with a clinically suspected fracture of the hip, we retrospectively reviewed the MRI scans of the 35 patients who had no evidence of a fracture on their plain radiographs. In eight of these patients MR scanning excluded a fracture but the remaining 27 patients had an abnormal scan: one with a fracture of the pubic ramus, and in the other 26 a T(1)-weighted coronal MRI showed a hip fracture with 100% sensitivity. T(2)-weighted imaging was undertaken in 25 patients, in whom the diagnosis could not be established with this scanning sequence alone, giving a sensitivity of 84.0% for T(2)-weighted imaging. If there is a clinical suspicion of a hip fracture with normal radiographs, T(1)-weighted coronal MRI is the best sequence of images for identifying a fracture.
Asunto(s)
Fracturas del Cuello Femoral/diagnóstico , Fracturas Cerradas/diagnóstico , Distribución por Edad , Anciano , Anciano de 80 o más Años , Diagnóstico Precoz , Femenino , Fracturas Cerradas/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
The family Picornaviridae includes several viruses of great economic and medical importance. Poliovirus replicates in the human digestive tract, causing disease that may range in severity from a mild infection to a fatal paralysis. The human rhinovirus is the most important etiologic agent of the common cold in adults and children. Foot-and-mouth disease virus (FMDV) causes one of the most economically important diseases in cattle. These viruses have in common a capsid structure composed of 60 copies of four different proteins, VP1 to VP4, and their 3D structures show similar general features. In this study we describe the differences in stability against high pressure and cold denaturation of these viruses. Both poliovirus and rhinovirus are stable to high pressure at room temperature, because pressures up to 2.4 kbar are not enough to promote viral disassembly and inactivation. Within the same pressure range, FMDV particles are dramatically affected by pressure, with a loss of infectivity of more than 4 log units observed. The dissociation of polio and rhino viruses can be observed only under pressure (2.4 kbar) at low temperatures in the presence of subdenaturing concentrations of urea (1-2 M). The pressure and low temperature data reveal clear differences in stability among the three picornaviruses, FMDV being the most sensitive, polio being the most resistant, and rhino having intermediate stability. Whereas rhino and poliovirus differ little in stability (less than 10 kcal/mol at 0 degrees C), the difference in free energy between these two viruses and FMDV was remarkable (more than 200 kcal/mol of particle). These differences are crucial to understanding the different factors that control the assembly and disassembly of the virus particles during their life cycle. The inactivation of these viruses by pressure (combined or not with low temperature) has potential as a method for producing vaccines.
Asunto(s)
Cápside/química , Picornaviridae/química , Adulto , Animales , Aphthovirus/química , Fenómenos Biofísicos , Biofisica , Bovinos , Línea Celular , Niño , Frío , Células HeLa , Humanos , Modelos Moleculares , Picornaviridae/patogenicidad , Picornaviridae/fisiología , Poliovirus/química , Presión , Conformación Proteica , Desnaturalización Proteica , Rhinovirus/química , Termodinámica , Vacunas Virales/aislamiento & purificaciónRESUMEN
The effect of prostaglandins (PGA1 and PGB2) on the replication of Mayaro virus was studied in Vero cells. PGA1 and PGB2 antiviral activity was found to be dose-dependent. However, while 10 µg/ml PGB2 inhibited virus yield by 60 percent, at the same dose PGA1 suppressed virus replication by more than 90 percent. SDS-PAGE analysis of [35S]-methionine-labelled proteins showed that PGA1 did not alter cellular protein synthesis. In infected cells, PGA1 slightly inhibited the synthesis of protein C, while drastically inhibiting the synthesis of glycoproteins E1 and E2
Asunto(s)
Animales , Alphavirus/fisiología , Prostaglandinas A/farmacología , Prostaglandinas B/farmacología , Células Vero/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Infecciones por Alphavirus/tratamiento farmacológico , Alphavirus/efectos de los fármacos , Alphavirus/crecimiento & desarrollo , Glicoproteínas/biosíntesis , Metionina/análisis , Prostaglandinas A/metabolismo , Prostaglandinas A/uso terapéutico , Prostaglandinas B/metabolismo , Prostaglandinas B/uso terapéutico , Proteína C/biosíntesisRESUMEN
The effect of prostaglandins (PGA1 and PGB2) on the replication of Mayaro virus was studied in Vero cells. PGA1 and PGB2 antiviral activity was found to be dose-dependent. However, while 10 micrograms/ml PGB2 inhibited virus yield by 60%, at the same dose PGA1 suppressed virus replication by more than 90%. SDS-PAGE analysis of [35S]-methionine-labelled proteins showed that PGA1 did not alter cellular protein synthesis. In infected cells, PGA1 slightly inhibited the synthesis of protein C, while drastically inhibiting the synthesis of glycoproteins E1 and E2.