Characterization of metalloprotease cleavage products of human articular cartilage

OBJECTIVE: To identify, characterize, and compare proteolysis peptide products generated by metalloprotease digests of human articular cartilage. METHODS: Human articular cartilage was digested by the addition of exogenous metalloproteases, including matrix metalloproteinases 2, 3, 8, 9, 12, and 13 and aggrecanases ADAMTS-4 and ADAMTS-5. Proteolyzed peptide products were identified by proteomics methods using mass spectrometry. RESULTS: Complete sequences of the peptides proteolyzed from human articular cartilage, including N- and C-termini and hydroxylated posttranslational modifications, were determined. A wide variety of peptides, originating from types I, II, and III collagen, biglycan, prolargin, fibromodulin, fibronectin, decorin, cartilage oligomeric matrix protein, cartilage intermediate-layer protein, megakaryocyte-stimulating factor, mimecan, aggrecan, and lumican, was analyzed following metalloprotease digestion. Release of peptides varied as a function of time, enzyme specificity, and abundance. Specific type II collagen peptide biomarkers, including those containing the three-quarter-length fragment cleavage site and those containing the domains for helical peptide of type II collagen and C-telopeptide of type II collagen, were observed after release by selected proteases. CONCLUSION: The use of intact cartilage instead of purified protein substrates in the assay allowed for the identification of novel potential substrates and cleavage sites for individual enzymes under more physiologically relevant conditions. Characterization of these cartilage matrix peptides may help in the development of pharmacodynamic biomarkers of cartilage degradation, and also may contribute to an understanding of the bioactive peptides important in chondrocyte signaling.     

The Effects of Passive Smoking on the Six-Minute Walk Test in Obese Pediatric Cases

Objective: The aim of this study was to evaluate whether exposure to second-hand smoke affected the six-minute walk test (6MWT) of obese non-asthmatic pediatric cases.Methods: Obese pediatric patients (body mass index >95th p) with no existing co-morbidities were included in the study. Smoke exposure was assessed with a self-reported questionnaire completed by the parents. The subjects were divided into two groups: Group 1 consisting of obese children exposed to passive smoking and Group 2 of obese children not exposed to passive smoking. In addition to 6MWT, spirometric flow and volume, including forced expiratory volume in 1 s and peak expiratory flow rate, were also measured in all subjects. The results of the 6MWT were assessed to determine any association with passive smoking.Results: The study included 75 obese pediatric cases (40 male, 35 female) with a mean age of 9.06±0.97 years. The 6MWT results in Group 1 was 501.88±62.12 meters and in Group 2 559.63±72.93 meters. The difference was statistically significant (p=0.001).Conclusions: Passive smoking may negatively affect the respiratory and cardiovascular capacity in obese children, who are already at risk of lower cardiopulmonary function. The evaluation of 6MWT in these pediatric patients may be useful for monitoring and families should be warned about potential problems due to smoking.     

D-dimer level predicts in-hospital mortality in patients with infective endocarditis: A prospective single-centre study

Background

Increased circulating D-dimer levels have been correlated with adverse outcomes in various clinical conditions. To our knowledge, the association of on-admission D-dimer and in-hospital mortality in infective endocarditis (IE) has not been investigated. We hypothesized that increased on-admission D-dimer levels would correlate with adverse outcomes when prospectively studied in patients with IE.

Methods

In this prospective study, a total of 157 consecutive patients with the definite IE diagnosis met the inclusion criteria and underwent testing for on-admission D-dimer and CRP assays. The outcome measure was in-hospital death from any cause.

Results

In-hospital mortality occurred in 40 (26%) patients. Increased levels of plasma D-dimer (5.1 ± 1.7 vs 1.9 ± 0.8, p < 0.001), CRP [45(13-98) vs 12(5–28), p < 0.001] were found in dead patients compared with those survived. In addition to S. aureus infection, increased leukocyte count, end-stage renal disease, LVEF < 50%, vegetation size of > 10 mm, perivalvular abscess, on-admission D-dimer (HR: 1.32; 95% CI: 1.24-1.40; p < 0.001) and CRP (HR: 1.18; 95% CI: 1.09-1.36; p = 0.001) levels were significantly associated with in-hospital mortality. Furthermore, the sensitivity and specificity of D-dimer ≥ 4.2 mg/L in predicting in-hospital death in IE were 86% and 85%, respectively. Moreover, the sensitivity and specificity of CRP levels ≥ 13.6 mg/L were 72% and 69%, respectively.

Conclusion

Our findings suggest that on-admission D-dimer level may be a simple, available and valuable biomarker that allows us to identify high-risk IE patients for in-hospital mortality. D-dimer ≥ 4.2 mg/L, CRP ≥ 13.6 mg/L were independently associated with IE related in-hospital death.     

Saddle nose deformity, palatal perforation and truncus arteriosus in a patient with Crohn’s disease

Crohn’s disease (CD) is a chronic granulomatous inflammatory bowel disease which may also involve the extraintestinal organs such as joints, liver, skin and perianal tissue. Involvement of the nasal cavity is quite rare in CD. This case report presents a 28-year-old girl with CD and saddle nose deformity, alar collapse and palatal perforation as extraintestinal manifestations of the disease in addition to persistent truncus arteriosus-type 4.     

Segmental vitiligo in a patient with thoracic outlet syndrome

Reported here is a 35-year-old man with findings of thoracic outlet syndrome and bilateral segmental vitiligo on C8–T1 dermatomes. The possible causal relationship between the two disorders under the common denominator of cervical sympathetic involvement is discussed for the first time in the literature.