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OBJECTIVE: To investigate changes in the circulating levels of the C-telopeptide of type II collagen (CTX-II) with relation to disease onset and structural damage of cartilage in a rodent model of collagen-induced arthritis (CIA), and to investigate immunolocalization of the CTX-II epitope in the articular cartilage of affected joints. METHODS: Seven-week-old female Lewis rats were immunized with type II collagen and monitored using blood sampling at weekly intervals. At study termination (day 23), the animals were killed, synovial fluid was collected, and the affected joints were scored macroscopically for disease severity and underwent immunohistochemical evaluation. RESULTS: At the time of disease onset (day 15), which was characterized by redness and swelling of the affected joints (mean +/- SD macroscopic severity score 9.1 +/- 1.6), there was a 355% increase in serum CTX-II levels. The early change in serum CTX-II from day 0 to day 15 showed a significant association with the severity of cartilage damage (r = 0.61, P < 0.01). Immunostaining revealed extensive presence of the CTX-II epitope in the damaged, uncalcified cartilage tissue. CONCLUSION: The elevation in serum CTX-II concomitant with the onset of disease and proportional to cartilage damage demonstrates that CTX-II is a sensitive diagnostic tool for monitoring joint disease in the rodent model of CIA. Furthermore, the immunohistochemical findings are consistent with the concept that the major source of serum CTX-II is the damaged articular cartilage. [ABSTRACT FROM AUTHOR]

Objective: In this study, muscle involvement assessed by MRI and levels of GMPPB and glycosylation of α-dystroglycan expression in muscle were examined in patients with limb-girdle muscular dystrophy (LGMD) type 2T., Methods: Six new patients with genetically verified mutations in GMPPB were studied. T1-weighted magnetic resonance images were obtained in 4 participants. Muscle strength and potential involvement of extramuscular organs were examined. Glycosylation of α-dystroglycan in muscle was studied, and GMPPB and α-dystroglycan expression was analyzed by Western blotting. Prevalence of LGMD2T was calculated from the total LGMD population in Denmark. GMPPB was sequenced in all unclassified cases., Results: Two patients carried 3 new mutations in GMPPB . The other 4 patients carried previously described pathogenic mutations in GMPPB . MRI showed that the paraspinal muscles were the most affected, followed by involvement of hamstrings. Our results showed a loss of glycosylation of α-dystroglycan as well as secondary loss of merosin expression on Western blotting. The prevalence of LGMD2T in the Danish cohort of patients with LGMD is 1.5%., Conclusions: The new findings of this study are (1) the consistent finding of a preferential affection of paraspinal and hamstring muscles in LGMD2T, (2) 3 new mutations in GMPPB, (3) variable loss of glycosylation tested with IIH6 and VIA4 antibodies, and (4) a prevalence of LGMD2T of 1.5% in a well-characterized Danish LGMD cohort.

Background: To investigate the most effective duration of combined psychotherapy and pharmacotherapy for achieving remission and preventing relapse in depressive patients as compared to pharmacotherapy alone., Methods: A systematic review of English articles using PubMed, EMBASE, Web of Science, the Cochrane Library, and PsychINFO was performed in September 2009. Clinical studies comparing pharmacotherapy alone with pharmacotherapy in combination with a psychological intervention for depression treatment that reported response, remission or relapse as outcomes were included in the analysis. For each of the studies, clinical binary outcomes such as response, remission or relapse were extracted., Results: All pooled analyses were based on random-effects models. Twenty-one article describing the influence of additional psychotherapy on remission and 15 articles reporting the influence on relapse in depression were included in the analysis. Patients receiving combined treatment experienced remission more often than those receiving pharmacotherapy alone, with the highest odds ratio OR, 2.36; 95% CI, 1.58-3.55 observed at 4months after commencing the treatment. Patients receiving pharmacotherapy alone also demonstrated a higher risk for relapse compared to those receiving combined treatment., Limitations: We restricted our search to only English language publications. Studies investigating relapse or recurrence rates are often of small size., Conclusion: Pharmacotherapy enhanced with psychotherapy is associated with a higher probability of remission and a lower risk of relapse, as compared to antidepressants alone for depression treatment. Receiving psychotherapy in both the acute and continuation phases is the most effective option. Further research is needed to investigate the influence of additional psychotherapy on different patients., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The goal of this article is to review the literature for evidence supporting an association between polymorphisms within drug target genes and clinical outcomes for treating depression, with a purpose to identify a research area having the most promising potential to be introduced into clinical settings, and thus, discussing the perspectives of genotyping in antidepressant therapy. A total of 67 articles were identified. Polymorphic sites within the serotonin transporter gene promoter, 5-HTTLPR, were the most studied polymorphisms. All except three articles were designed as cohort studies. The other three articles included two meta-analyses and one decision-analytic model. The main finding from these meta-analyses was that the l variant was associated with a better response to selective serotonin reuptake inhibitors. The main conclusion from the decision-analytic model study was that performing genetic testing before prescribing antidepressant treatment may lead to greater numbers of patients experiencing remission early in treatment. Clinical outcomes of genotyping this polymorphism were evaluated by improvement of depression score, odds ratio and absolute risk reduction.

Objective: To investigate whether oral calcitonin treatment influences the increases in type II collagen (CII) degradation and related surface erosions of articular cartilage in ovariectomized rats., Methods: Fifty rats were randomly allocated into 1 of the 5 following intervention groups: sham-operated, ovariectomy, ovariectomy plus subcutaneously implanted 17beta-estradiol pellet, ovariectomy plus 2 mg/kg salmon calcitonin plus 50 mg/kg 5CNAC (carrier), or ovariectomy plus 50 mg/kg 5CNAC. Each treatment was administered for 9 weeks after the ovariectomy. Blood samples for biochemical marker analysis were collected from fasting animals at baseline, on day 3, and after 1, 2, 4, 6, and 9 weeks. CII degradation was quantified by specific immunoassay, and the changes in severity scores of articular cartilage erosions were visualized and scored in histologic sections of the knees., Results: Ovariectomy resulted in a marked increase in serum levels of C-telopeptide of type II collagen (CTX-II) (P < 0.001), which could be effectively reversed by 17beta-estradiol supplementation. Oral administration of calcitonin elicited similar decreases in serum levels of CTX-II (P < 0.001). Histologic scoring of cartilage erosion showed significantly less cartilage erosion in calcitonin-treated ovariectomized rats versus control ovariectomized rats that were untreated or treated with 5CNAC alone. (P < 0.01)., Conclusion: The in vivo effects of calcitonin in rats suggest that calcitonin is able to counteract CII degradation and the accompanying structural disintegration of articular cartilage promoted by estrogen deficiency. Clinical assessment of the chondroprotective potential of calcitonin in postmenopausal women seems warranted.

Objective: To investigate how the time of initiation influences the effects of estrogen therapy on type II collagen (CII) turnover and the structural integrity of articular cartilage in ovariectomized rats and to determine whether estrogen exerts direct effects on the catabolic function of chondrocytes ex vivo., Methods: A total of 46 Sprague-Dawley rats were distributed into 1 of the following treatment groups: 1) ovariectomy, 2) ovariectomy plus early estrogen therapy, 3) ovariectomy plus delayed estrogen therapy, or 4) sham operation. Cartilage turnover was estimated by measuring the serum levels of C-telopeptide of type II collagen (CTX-II). Cartilage lesions at week 9 were quantified using a published scoring technique. The presence of the CTX-II epitope in articular cartilage was assessed by immunohistochemistry. The effects of estrogen (1-100 nM) on chondrocytes were investigated in bovine cartilage explants subjected to catabolic cytokines (tumor necrosis factor alpha [TNFalpha] and oncostatin M [OSM])., Results: In ovariectomized rats, estrogen therapy evoked significant decreases in serum CTX-II independently of the time of initiation; yet, delayed initiation resulted in diminished efficacy in terms of preventing cartilage lesions. CTX-II fragments were present in articular cartilage, colocalizing with early lesions at the cartilage surface. In untreated animals, the early relative increases in serum CTX-II were proportional to the severity of cartilage lesions at week 9 (r = 0.73, P < 0.01). Estrogen significantly and dose-dependently countered CTX-II release from TNFalpha plus OSM-stimulated cartilage explants ex vivo., Conclusion: Our results suggest that estrogen counters the acceleration of CII degradation and related structural alterations, and these benefits can be maximized by early initiation after menopause. The protective effect of estrogen seems to involve direct inhibition of the catabolic function of chondrocytes.