Sesamin Stimulates Osteoblast Differentiation Through p38 and ERK1/2 MAPK Signaling Pathways

ABSTRACT: BACKGROUND: Osteoporosisis a worldwide health problem predominantly affecting post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic patients lag behind comparable investigation of therapeutic strategies focusing on the bone resorption process. Sesamin, a major lignan compound found in Sesamun indicum Linn., has a variety of pharmacological effects, though its activity on bone cell function is unclear. Herein we examine the effect of this lignan on osteoblast differentiation and function. METHOD: Cell cytotoxicity and proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 hour of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were detected after 24 hour of sesamin treatment. ALP activity was measured at day 7, 14 and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of osteogenic media supplement with or without sesamin for 21 days and then stain with Alizarin Red S staining. MAPK signaling pathway activation was observed by using western blotting. RESULTS: Sesamin promoted the expression COL1, ALP, OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up-regulate OPG and down-regulate RANKL gene expression. ALP activity also significantly increased after sesamin treatment. Interestingly, sesamin induced formation of mineralized nodules in adipose derived stem cells (ADSCs) as observed by Alizarin Red S staining; this implies that sesamin has anabolic effects both on progenitor and committed cell stages of osteoblasts. Western blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in hFOB1.19. CONCLUSIONS: The data suggest that sesamin has the ability to trigger osteoblast differentiation by activation of the MAPK signaling pathway (p38 and ERK) and possibly indirectly regulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising phytochemical that could be developed for osteoporotic therapy.     

Intramuscular absorption and biodistribution of dexamethasone from non-aqueous emulsions in the rat

Non-aqueous or oil-in-oil emulsions may be used as reservoirs to deliver lipophilic or hydrolytically unstable drugs. Emulsions of castor oil-in-silicone oil (co/so) release drugs slowly in vitro. To investigate the potential use of such formulations as depot preparations in vivo, drug absorption and distribution from an intramuscular injection site to various organs in the rat was studied. (3)H-dexamethasone (0.1mg/kg) was incorporated into the castor oil (disperse phase) of co/so emulsions and in castor oil-in-water (co/w) emulsions, the latter serving as control. (3)H-dexamethasone was absorbed after intramuscular injection of co/w emulsions, reaching a plasma C(max) of 0.078 microg/ml at 2.0 h (T(max)). For co/so emulsions, a lower C(max) (0.048 microg/ml) was observed with a longer T(max) (4.0 h). No significant difference was found between the two formulations in the area under the plasma concentration-time curve (AUC(infinity)), or in clearance (CL). Administration of (3)H-dexamethasone in the co/so emulsion improved the mean residence time (MRT) and the elimination half-life (t(1/2)) in comparison to the co/w emulsion. The clearance of (3)H-dexamethasone from the co/so emulsions at the injection site was also slower and at 4.0 h post-injection the amount of drug remaining in the muscle was found to be eight times higher than with the co/w emulsions. For both formulations, a high uptake of (3)H-dexamethasone was identified in the liver and kidneys whereas smaller amounts were found in other tissues. Non-aqueous emulsions could be considered as depot formulations for sustained release drug delivery, but further studies on the choice of the continuous phase are necessary to optimize effects.     

Participatory capacity building in occupational disease surveillance among primary care unit (pcu) health personnel

This study aimed to demonstrate participatory capacity building regarding occupational disease surveillance (ODS) could enable the Primary Care Unit (PCU) health personnel provide satisfactory occupational health services for workers in the community. A needs assessment was carried out to identify gaps in PCU health personnel skills and knowledge so these areas could be strengthened. An ODS training program was developed. Fifty-nine health personnel participated in a 5 day workshop and received instructions regarding a wide range of occupational diseases, surveillance methods, prevention measures, and Ministry of Public Health (MOPH) surveillance systems. Participants self reported positive changes in knowledge and skills, as well as a high level of satisfaction with the workshop. However, many participants noted barriers to consistently implementing reporting procedures.     

Epidemiology and postoperative outcomes of atypical femoral fractures in older adults: A systematic review

Objective

To review the literature on epidemiology and postoperative outcomes particularly surgical, functional and quality of life of atypical femoral fractures (AFFs) in the older population (aged ≥65 years) using the first and second American Society of Bone Mineral Research (ASBMR) Task Force consensus definition.

Methods

Electronic search for articles on AFFs and bisphosphonates published in English was performed. Eligible studies were reviewed systematically in relation to (a) the epidemiology of AFFs in older people and (b) postoperative outcomes of AFFs.

Results

Twenty-three studies on AFFs were included: 14 on epidemiology and 11 on treatment outcomes (two articles reported on both aspects). The epidemiological studies showed that the incidence of AFFs is low (3.0-9.8 per 100,000 person-years) but relative risk increased with longer duration of bisphosphonates use, especially after more than three years. Most cases of AFFs occurred in older people aged 65 years and above. However, in six studies, the mean age of patients with bisphosphonate-related AFFs is younger than those with typical proximal femoral fractures (mean age range of 66–75 years versus 75-89 years respectively). Varying postoperative and functional outcomes have been reported but differences in study population, management approaches and endpoints may account for these variations. For incomplete AFFs, prophylactic surgical intervention is potentially beneficial.

Conclusion

The benefits of bisphosphonates in reducing osteoporotic fractures still outweigh the risk of AFFs in view of its low absolute risk, when the ASBMR Task Force criteria for this type of fracture were applied. The risk of AFFs in different age groups is not well defined but tends to affect the younger patients more (aged <65 years) as compared to the older population (aged ≥65 years). Evidence supporting different types of treatment in AFFs such as intramedullary or extramedullary surgical devices and the use of teriparatide, a parathyroid hormone analogue, is not yet well established.

     

Risk indicators of periodontal disease in older Thai adults

BACKGROUND: The aim of this study was to identify risk indicators for periodontitis using cross-sectional data from a group of older Thai adults. METHODS: The study group consisted of 2,005 individuals, aged 50 to 73 years old. They received detailed medical examinations and periodontal examinations including plaque score, probing depth, and clinical attachment level. These individuals were categorized into mild, moderate, or severe periodontitis if mean clinical attachment level was <2.5 mm, 2.5 to 3.9 mm, or > or = 4.0 mm, respectively. The degree of association between the severity of periodontitis and various independent variables was investigated using multinomial logistic regression analysis. RESULTS: The percentage of subjects classified as mild, moderate, and severe periodontitis was 30.5, 53.6, and 15.9, respectively. The prevalence of severe periodontitis was higher in males and increased with age. In univariate analysis, older subjects, males, less educated persons, persons with lower income, persons with higher plaque score, smokers, drinkers, and diabetics were more likely to have both moderate and severe periodontitis. In multivariate analysis, males, less educated persons, persons with higher plaque score, and current smokers were more likely to have moderate periodontitis. Three additional factors including older age, former smokers, and diabetes significantly increased the odds for having severe periodontitis. Income, alcohol consumption, body mass index, and waist circumference had no significant effects on periodontal disease severity in the multivariate model. CONCLUSIONS: Our data suggest that age, gender, education, oral hygiene status, smoking, and diabetes are significantly associated with periodontal disease severity in this study group. Longitudinal studies will establish whether these variables are true risk factors.     

Coronal Alignment of Fixed-Bearing Unicompartmental Knee Arthroplasty Femoral Component May Affect Long-Term Clinical Outcomes

BackgroundThis study aims to investigate the clinical effects of femoral component coronal alignment in a cohort of fixed-bearing unicompartmental knee arthroplasty with clinical and radiological follow-up of 10 years.MethodsProspectively collected registry data of 264 consecutive, cemented, primary fixed-bearing medial unicompartmental knee arthroplasties performed at a single institution from 2004 to 2007 were reviewed. Femoral component coronal angle (FCCA), tibial component coronal angle, and hip-knee-ankle angle were measured on postoperative radiographs. Patients were grouped into acceptable (AG ≤ 3°) and outlier (OG > 3°) groups according to absolute FCCA. Clinical assessment at 6-month, 2-year, and 10-year follow-up was performed using Knee Society Knee and Function Scores, Oxford Knee Score (OKS), and Short Form-36. Fulfillment of expectations, satisfaction, and implant survivorship was recorded.ResultsThere was no significant difference in demographics, tibial component coronal angle, hip-knee-ankle angle, and sagittal parameters in both groups. The OG had poorer OKS at 10 years and a larger deterioration from 2 to 10 years compared to AG (P = .02). Increase in FCCA was associated with deterioration in 2-year OKS (adjusted ß = 0.23, P = .01), 10-year OKS (adjusted ß = 0.26, P = .03), and 2-year Short Form-36 physical component score (adjusted ß = ?0.44, P = .01). Expectation fulfillment at 2 years was lower in the OG vs the AG (88% vs 100%, P = .03). Both groups had similar 10-year survivorship (99% vs 98%, P = .65).ConclusionsFCCA may affect long-term clinical outcomes, but not short-term clinical outcomes nor 10-year survivorship. Given similar limb alignment, coronal and sagittal component positioning, a larger FCCA was associated with poorer outcomes at 10-year follow-up.     

The effects of green pit viper (Trimeresurus albolabris and Trimeresurus macrops) venom on the fibrinolytic system in human.

Green pit viper (Trimeresurus albolabris and Trimeresurus macrops) venom was found to have a thrombin-like effect in vitro but cause a defibrination syndrome in vivo. The effects of venom on fibrinolytic system have not been well characterized. This knowledge can help to define the roles of antifibrinolytic therapy, give insights in fibrinolytic system regulation and potentially lead to identification of a new profibrinolytic agent from this venom. Forty-six cases of green pit viper bites were studied for various coagulation and fibrinolytic parameters and correlated with serum venom levels measured by ELISA. Fibrinolytic system activation is very common as indicated by low plasminogen (50%), low antiplasmin (56.5%) and elevated fibrin-fibrinogen degradation products (FDPs, 97.4%) levels. FDP test is very sensitive and a normal level is useful for exclusion of systemic envenomation. In contrast to some other models of defibrination syndrome, such as Russell viper (Daboia russelli siamensis), elevation of plasminogen activator activity (PA) was found indicating a hyperfibrinolytic state. Definite increase in tissue-type plasminogen activator (t-PA) antigen (p = 0.00075) with a modest elevation of its inhibitor plasminogen activator inhibitor-1 (PAI-1) (p = 0.27) probably contributes to this effect. This supports the idea that the balance between plasminogen activators and inhibitors can determine fibrinolytic responses in pathologic states. Fibrinopeptide A levels were markedly elevated (68.43 +/- 51.57 ng/ml in cases and 2.83 +/- 3.80 ng/ml in control, p < 0.0001) and correlated well with clinical severity suggesting that the fibrin deposition from the thrombin-like effect is the main mechanism of fibrinolysis. Therefore, antifibrinolytic agents probably have no role in treatment. However, the components of green pit viper venom that have these profibrinolytic effects in human are interesting and should be further identified.     

Lupus nephritis and Raynaud’s phenomenon are significant risk factors for vascular thrombosis in SLE patients with positive antiphospholipid antibodies

This study is aimed to determine the predictors of nongravid vascular thrombosis in systemic lupus erythematosus (SLE) patients with positive antiphospholipid antibodies (SLE-aPL). A cohort of 67 SLE-aPL patients who had at least one positive test for lupus anticoagulant (LA), anticardiolipin (aCL), or anti-beta2glycoprotein-1(B2) was examined. Main outcome was the presence of vascular thrombosis. Association between thrombosis and risk factors was examined by contingency table. The odds ratio (OR) of significant predictors was determined by logistic regression. Three percent of patients were LA⁺, 6% were aCL⁺, 31% were B2⁺, 3% were aCL⁺LA⁺, 35.8% were aCL⁺B2⁺, 7.5% were LA⁺B2⁺, and 13.4% were positive for all tests. As for clinical manifestations, 79% had lymphopenia, 76% had lupus nephritis (LN), 41.8% had autoimmune hemolytic anemia, 34.3% had thrombocytopenia, 20.9% had abortion, and 19.4% had Raynaud’s phenomenon (RP). Thrombosis occurred in 26 patients. The prevalence of thrombosis for SLE-aPL was 38.8%. Thrombosis was observed more frequently in patients with LA⁺ (12 of 18) than the others (14 of 49; p = 0.01). Two-by-two table showed that oral contraceptive and LN were significantly associated with increased risk of thrombosis, while lymphopenia and antimalarials were significantly associated with decreased risk of thrombosis. Multivariate analysis confirmed that LN and RP were associated with increased risk of thrombosis (OR = 6.2 and 3.2; p = 0.005 and 0.008), while lymphopenia and antimalarials were associated with decreased risk of thrombosis (OR = 0.86 and 0.18; p = 0.02 and 0.034). LA is the strongest test to determine the risk of thrombosis in SLE-aPL. The presence of LN and RP strongly predicts thrombosis, while lymphopenia and antimalarials are protective. These findings help to identify patients who may benefit from prophylactic therapy.