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Decreased Serum Levels (decreased + serum_level)
Selected AbstractsMonthly Oral Ibandronate Therapy in Postmenopausal Osteoporosis: 1-Year Results From the MOBILE StudyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2005Paul D Miller MD Abstract Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year. Introduction: Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis. Although yet to be prospectively shown in osteoporosis, evidence from randomized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence. Ibandronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of >2 months. This report presents comparative data on the efficacy and safety of monthly and daily oral ibandronate regimens. Materials and Methods: MOBILE is a 2-year, randomized, double-blind, phase III, noninferiority trial. A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ibandronate regimens: 2.5 mg daily, 50 mg/50 mg monthly (single doses, consecutive days), 100 mg monthly, or 150 mg monthly. Results: After 1 year, lumbar spine BMD increased by 3.9%, 4.3%, 4.1%, and 4.9% in the 2.5, 50 /50, 100, and 150 mg arms, respectively. All monthly regimens were proven noninferior, and the 150 mg regimen superior, to the daily regimen. All monthly regimens produced similar hip BMD gains, which were larger than those with the daily regimen. All regimens similarly decreased serum levels of C-telopeptide, a biochemical marker of bone resorption. Compared with the daily regimen, a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine (6%) or total hip BMD (3%). All regimens were similarly well tolerated. Conclusions: Monthly ibandronate is at least as effective and well tolerated as the currently approved daily ibandronate regimen in postmenopausal osteoporosis. [source] Serum amino-terminal propeptide of type III procollagen and 7S domain of type IV collagen correlate with hepatic iron concentration in patients with chronic hepatitis C following ,-interferon therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2001Ichiro Shimizu Abstract Background: It has been reported that chronic infection with hepatitis C virus is associated with excess iron deposits in the liver of subjects who are neither alcoholics nor recipients of blood transfusions. However, little is known about the relationship between hepatic iron concentration (HIC) and the serum levels of hepatic fibrogenesis markers, which were caused by interferon therapy for chronic hepatitis C. Therefore, changes in the serum amino-terminal propeptide of type III procollagen (P-III-P) and the 7S domain of type IV collagen (7S-IV) in 16 patients treated with ,-interferon (IFN-,) were studied, and their HIC and histological assessment evaluated. Hepatic iron concentrations were measured by using liver biopsy specimens obtained before and 6 months after the cessation of treatment. Methods and Results: Eight subjects (50%) who had normal alanine transaminase levels at 6 months after therapy showed significantly lowered HIC, and attenuated hepatic iron staining with decreased serum levels of P-III-P and 7S-IV compared to the remaining subjects. The HIC was significantly correlated with the serum levels of P-III-P and 7S-IV in all subjects. Conclusions: These findings suggest that IFN-, treatment may decrease stimuli for fibrogenesis, at least in part, by reducing the hepatic iron deposition in patients with chronic hepatitis C. [source] Addition of bisphosphonate to antibiotic and anti-inflammatory treatment reduces bone resorption in experimental Staphylococcus aureus -induced arthritisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2007Margareta Verdrengh Abstract Bacterial arthritis is a disease with high morbidity leading to rapidly progressive bone resorption. We have shown earlier that treatment with antibiotics in combination with corticosteroids decreases joint inflammation and mortality but does not significantly affect bone/cartilage destruction of the joints. This study was performed to assess the effect of treatment with bisphosphonate [zoledronic acid (ZA)] in combination with antibiotics and corticosteroids, on the course and outcome of Staphlococcus aureus -induced arthritis. Three days after intravenous inoculation with S. aureus, mice were treated with antibiotics alone, ZA alone, ZA and antibiotics, or ZA combined with antibiotics and corticosteroids, respectively. One group served as controls and received PBS. Clinical assessment of arthritis was performed as well as histological analysis of bone and cartilage destruction in the joints. One femur from each mouse was collected for bone mineral density (BMD) analysis. In addition, serum levels of type I collagen fragments (RatLaps), and osteocalcin, markers for osteoclastic and osteoblastic activity, respectively, were analyzed. Mice treated with ZA and antibiotics or with ZA in combination with antibiotics and corticosteroids lost significantly less in trabecular bone density compared to infected control mice. Furthermore, the addition of corticosteroids to animals treated with ZA and antibiotics, significantly decreased serum levels of RatLaps and osteocalcin, compared to animals treated with ZA and antibiotics or ZA alone. Treatment with bisphosphonates in combination with antimicrobial agents and corticosteroids significantly decreases the activity of osteoclasts in septic arthritis, thereby reducing the risk of skeletal destruction. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] The cytoprotective effects of addition of activated protein C into preservation solution on small-for-size grafts in ratsLIVER TRANSPLANTATION, Issue 1 2010Naohisa Kuriyama Small-for-size liver grafts are a serious obstacle for partial orthotopic liver transplantation. Activated protein C (APC), a potent anticoagulant serine protease, is known to have cell-protective properties due to its anti-inflammatory and antiapoptotic activities. This study was designed to examine the cytoprotective effects of a preservation solution containing APC on small-for-size liver grafts, with special attention paid to ischemia-reperfusion injury and shear stress in rats. APC exerted cytoprotective effects, as evidenced by (1) increased 7-day graft survival; (2) decreased initial portal pressure and improved hepatic microcirculation; (3) decreased levels of aminotransferase and improved histological features of hepatic ischemia-reperfusion injury; (4) suppressed infiltration of neutrophils and monocytes/macrophages; (5) reduced hepatic expression of tumor necrosis factor , and interleukin 6; (6) decreased serum levels of hyaluronic acid, which indicated attenuation of sinusoidal endothelial cell injury; (7) increased hepatic levels of nitric oxide via up-regulated hepatic endothelial nitric oxide synthesis expression together with down-regulated hepatic inducible nitric oxide synthase expression; (8) decreased hepatic levels of endothelin 1; and (9) reduced hepatocellular apoptosis by down-regulated caspase-8 and caspase-3 activities. These results suggest that a preservation solution containing APC is a potential novel and safe product for small-for-size liver transplantation, alleviating graft injury via anti-inflammatory and antiapoptotic effects and vasorelaxing conditions. Liver Transpl 16:1,11, 2010. © 2009 AASLD. [source] Amelioration of collagen-induced arthritis and immune-associated bone loss through signaling via estrogen receptor ,, and not estrogen receptor , or G protein,coupled receptor 30ARTHRITIS & RHEUMATISM, Issue 2 2010Cecilia Engdahl Objective The effects of estrogen may be exerted via the nuclear estrogen receptors (ERs) ER, or ER, or via the recently proposed transmembrane estrogen receptor G protein,coupled receptor 30 (GPR-30). The purpose of this study was to elucidate the ER specificity for the ameliorating effects of estrogen on arthritis and bone loss in a model of postmenopausal rheumatoid arthritis (RA). Methods Female DBA/1 mice underwent ovariectomy or sham operation, and type II collagen,induced arthritis was induced. Mice were treated subcutaneously 5 days/week with the specific agonists propylpyrazoletriol (PPT; for ER,), diarylpropionitrile (DPN; for ER,), G1 (for GPR-30), or with a physiologic dose of estradiol. Clinical arthritis scores were determined continuously. At termination of the study, bone mineral density (BMD) was analyzed, paws were collected for histologic assessment, serum was analyzed for cytokines and markers of bone and cartilage turnover, and bone marrow was subjected to fluorescence-activated cell sorting. Results Treatment with PPT as well as estradiol dramatically decreased the frequency and severity of arthritis. Furthermore, estradiol and PPT treatment resulted in preservation of bone and cartilage, as demonstrated by increased BMD and decreased serum levels of bone resorption markers and cartilage degradation markers, whereas no effect was seen after DPN or G1 treatment. Conclusion In a well-established model of postmenopausal RA, ER,, but not ER, or GPR-30 signaling, was shown to ameliorate the disease and the associated development of osteoporosis. Since long-term treatment with estrogen has been associated with significant side effects, increased knowledge about the mechanisms behind the beneficial effects of estrogen is useful in the search for novel treatments of postmenopausal RA. [source] Retinoid ameliorates experimental autoimmune myositis, with modulation of Th cell differentiation and antibody production in vivoARTHRITIS & RHEUMATISM, Issue 10 2009Naho Ohyanagi Objective Polymyositis and dermatomyositis are chronic inflammatory muscle diseases. Retinoids are compounds that bind to the retinoic acid binding site of retinoic acid receptors and have biologic activities similar to those of vitamin A. Recent studies indicate that retinoids promote Th2 differentiation and suppress Th1 and Th17 differentiation in vitro. The present study was undertaken to examine the effects of a synthetic retinoid, Am80, on experimental autoimmune myositis as well as on Th phenotype development and antibody production. Methods Experimental autoimmune myositis was induced in SJL/J mice by immunization with rabbit myosin. Am80 was administered orally once daily. Its effects were evaluated by measurement of the numbers of infiltrating inflammatory cells, production of inflammatory cytokines in muscle, production of Th-specific cytokines by myosin-stimulated splenic T cells, and production of antimyosin antibodies in serum. Results In mice with experimental autoimmune myositis, orally administered Am80 significantly reduced the number of infiltrating inflammatory cells and the expression of tumor necrosis factor , and interleukin-1, (IL-1,) in muscle. Moreover, Am80 increased production of interferon-,, IL-4, and IL-10, but not IL-17, by myosin-stimulated splenic T cells of mice with experimental autoimmune myositis, suggesting that it could enhance differentiation into Th1 and Th2, but not Th17, in vivo. Am80 also decreased serum levels of IgG2a and IgG2b antimyosin antibodies, but did not affect levels of IgG1 antimyosin antibodies. In addition, it suppressed chemokine expression and activator protein 1 activity in myoblasts in vitro. Conclusion The synthetic retinoid Am80 has an inhibitory effect on experimental autoimmune myositis. It might regulate the development of Th phenotype and antibody production in vivo, in addition to its effects on cytokine and chemokine production. [source] | ||||||||||