ABSTRACT
OBJECTIVE: To investigate whether heterozygosity for a loss-of-function mutation in the gene encoding the alpha1 chain of type XI collagen (Col11a1) in mice (chondrodysplasia, cho) causes osteoarthritis (OA), and to understand the biochemical and biomechanical effects of this mutation on articular cartilage in knee and temporomandibular (TM) joints. METHODS: Articular cartilage from the knee and TM joints of mice heterozygous for cho (cho/+) and their wild-type littermates (+/+) was examined. The morphologic properties of cartilage were evaluated, and collagen fibrils were examined by transmission electron microscopy. Immunohistochemical staining was performed to examine the protein expression levels of matrix metalloproteinase 3 (MMP-3) and MMP-13 in knee joints. In 6-month-old animals, fixed-charge density was determined using a semiquantitative histochemical method, and tensile stiffness was determined using an osmotic loading technique. RESULTS: The diameter of collagen fibrils in articular cartilage of knee joints from heterozygous cho/+ mice was increased relative to that in control cartilage, and histologic analysis showed OA-like degenerative changes in knee and TM joints, starting at age 3 months. The changes became more severe with aging. At 3 months, protein expression for MMP-3 was increased in knee joints from cho/+ mice. At 6 months, protein expression for MMP-13 was higher in knee joints from cho/+ mice than in joints from their wild-type littermates, and negative fixed-charge density was significantly decreased. Moreover, tensile stiffness in articular cartilage of knee joints from cho/+ mice was moderately reduced and was inversely correlated with the increase in articular cartilage degeneration. CONCLUSION: Heterozygosity for a loss-of-function mutation in Col11a1 results in the development of OA in the knee and TM joints of cho/+ mice. Morphologic and biochemical evidence of OA appears to precede significant mechanical changes, suggesting that the cho mutation leads to OA through a mechanism that does not initially involve mechanical factors.
Subject(s)
Cartilage, Articular/physiology , Collagen Type XI/genetics , Osteoarthritis, Knee , Osteochondrodysplasias/genetics , Animals , Cartilage, Articular/pathology , Collagen/ultrastructure , Collagenases/metabolism , Genotype , Immunohistochemistry , Knee Joint/pathology , Knee Joint/physiopathology , Matrix Metalloproteinase 13 , Matrix Metalloproteinase 3/metabolism , Mice , Mice, Mutant Strains , Movement , Osteoarthritis, Knee/genetics , Osteoarthritis, Knee/pathology , Osteoarthritis, Knee/physiopathology , Osteochondrodysplasias/complications , Temporomandibular Joint/pathology , Temporomandibular Joint/physiopathology , Tensile StrengthABSTRACT
Nail biting is a common habit in children. In most cases, it is of cosmetic concern only; however, if not controlled, it can lead to serious morbidity. A case is presented of a child who developed osteomyelitis of a distal phalanx as a result of chronic nail biting.
Subject(s)
Nail Biting/adverse effects , Osteomyelitis/etiology , Child, Preschool , Fingers/diagnostic imaging , Fingers/pathology , Humans , Male , Osteomyelitis/diagnostic imaging , RadiographyABSTRACT
A specific and quantitative GLC method for the determination of griseofulvin in human plasma is described. The method involves extraction with ether, evaporation, addition of the internal standard dissolved in benzene, and GLC analysis using an electron-capture detector. The sensitivity of the method is 0.05 mug/ml of plasma. The results obtained with this specific GLC method were compared with the results obtained with the more frequently used spectroflurometric method by analyzing duplicate plasma samples obtained from 12 subjects following a single dose of griseofulvin. It was deduced that the 30% higher plasma levels obtained spectrofluormetrically were due to the coextraction and presence of the metabolite 6-demethylgriseofulvin in the assay solutions.
