Sea urchin Tripneustes gratilla is one of the valuable fishery products in Taiwan. The edible part of sea urchin is about 10% and the rest is regarded as waste. In this study, sea urchin shell was used here as an ingredient to synthesize magnesium substituted beta-tricalcium phosphate (β-TCMP). Shell powder of the echinoid Tripneustes gratilla was converted by hydrothermal reaction at 180°C for 24 h (referred as SU-180-24 product), and calcinated into tablet at 800°C for 4 h to form the target ingredient (SU-800-4 product). Then these products were tested for chemical composition analysis and bioassays. These products are confirmed to be rich in magnesium and constitute as β-TCMP. Results from bioassays showed that SU-180-24 and SU-800-4 products increased cell viability in human osteosarcoma cell (MG-63). Alkaline phosphatase (ALP) activity of MG-63 cell cultured with SU-800-4 tablet also showed significant increase when compared to commercial β-TCMP. It indicated that sea urchin's β-TCMP materials including SU-180-24 and SU-800-4 products exhibited the potential for applying as the bone graft material.
Cartilage can redistribute human body’s daily loads and decrease the friction force in the diarthrodial joints. However, it may be injured due to trauma, sports injury, biomechanical imbalance, and genetic disease. Microfracture (MF), osteochondral autograft transplantation (OAT), and autologous chondrocyte implantation (ACI) are the most common treatment procedures in the hospital. Recently, the concept of tissue engineering involving the combination of cells, scaffolds, and bioactive signals has inspired researchers. Our team of researchers synthesized a tri-copolymer from biological polymer by using gelatin, chondroitin-6-sulfate, and hyaluronic acid through cross-linking reaction. Lacuna formation could be seen in the tri-copolymer surrounding the chondrocytes, and some newly formed glycosaminoglycan was found in the engineered cartilage. Considering the dedifferentiation possibility of chondrocyte, bone marrow mesenchymal stem cells (BMSCs) become an ideal cell source for cartilage tissue regeneration, since they can be easily harvested from adult tissue, and be expanded in vitro. In an in-vivo porcine pilot study, the results showed that the defect site could be regenerated by BMSCs/collagen gel, and is formed with fibro/hyaline mixed cartilage tissue after implantation for six months. Several clinical studies using BMSCs for cartilage defect treatment were also conducted recently; clinical outcomes such as IKDC, Lysholm, and Tegner scores improved when the cartilage defects were repaired by several millions of mesenchymal stem cells, and there is no tumor formation after being treated with BMSCs during the 10-year follow-up. Moreover, recently a commercial BMSCs/collagen gel composite for cartilage repair was developed in Taiwan and clinical trial was conducted in 2008; the results showed that there is an improvement in IKDC and MRI scores during the nine-year follow-up. It seems that using an engineered cartilage made from BMSCs/collagen gel for cartilage defect treatment is a promising method.
This study aimed to evaluate the effectiveness of a novel calcitonin-loaded calcium phosphate composite bone cement in vitro and in vivo. The novel composite bone cements were composed of NuROs injectable bone graft substitute, type I collagen, and/or salmon calcitonin. The setting time, porosity, wettability, compressive strength, compressive modulus, and crystallographic structures of cement specimens were determined. Degradation rate, calcitonin release rate, and osteoinductivity were assessed in vitro. In addition, osteogenic effect was examined in a rabbit model of femoral defect. The results revealed that addition of collagen/calcitonin did not substantially alter physical properties and degradation rate of bone cement specimens. Calcitonin was released into culture medium in a two-phase manner. Osteogenic effect of conditioned medium derived from calcitonin containing bone cement was observed. Finally, de novo bone growth and bone mineralization across the bone defect area were observed in rabbits after implantation of composite bone cement specimens. In conclusion, this novel calcitonin-loaded composite calcium phosphate bone cement exhibits biocompatibility, bioresorbability, osteoinductivity, and osteoconductivity, which may be suitable for clinical use.
To utilize serum cystatin C (CysC) concentration to identify the daily dosage regimen of vancomycin (Van) for the treatment of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections.Serum Van, CysC, and serum and urine creatinine (Cr) concentrations were detected in 65 MRSA-infected patients. The estimated glomerular filtration rate (eGFR), Cr clearance (CLcr) and Van clearance (CLvan) were calculated and the correlation equation between CysC and CLvan was obtained using mathematical methods. Finally, the daily dosage equation of Van was derived according to pharmacokinetic theory.In the test sample, serum Cr was 183.27 ± 68.34 μmol/l, CLcr was 75.56 ± 30.02 ml/min, eGFR was 70.79 ± 40.79 ml/min, and serum CysC was 1.35 ± 0.61 mg/l. There was significant correlation between eGFR and CLcr (R2 = 0.8051, p = 0.000). Bland-Altman analysis showed an agreement of 96.9% (63/65) between eGFR and CLcr. eGFR was significantly correlated with CLvan (R2 = 0.8465, p = 0.000) and the correlation was significantly higher than that between CLvan and CLcr (R2 = 0.6367, p = 0.000). CysC fits a high correlated CLvan estimating equation (R2 = 0.9211, p = 0.000): CLvan(ml/min) = 64.4026 × (CysC)-1.1488. Accordingly, the predicted equation was created for calculation of the Van dosage to achieve the appropriate target steady-state serum concentration (Css): IR (the rate of continuous infusion, g/D) = 64.4026 × (CysC)-1.1488 × Css (mg/l) × (60/1,000) × 24.Serum CysC is a good marker of renal function in comparison with serum Cr for the dose determination of Van. CysC can estimate the daily dose of Van, and may improve therapeutic success rates of MRSA-infected patients.
Cold stress may produce hemodynamic perturbations but the underlying mechanisms are still not clear. Spectral analysis was used in this study to explore that sympathoadrenal activation could be involved in mechanisms of hemodynamic perturbations to cooling. Conscious rats after treatment with a control vehicle (saline) compared with withdrawal of sympathetic influences by ganglion blocker hexamethonium (HEX) or chemical sympathectomy guanethidine (GUA) were challenged by stressful cooling as acute immersing all four extremities in ice water (4 ± 2°C) for 10 min. Plasma nitric oxide (NO) and the appearance of Dichroitic notch (DN) were measured in comparison between treatment groups throughout the experimental course. Hemodynamic indices were telemetrically monitored, and variability of blood pressure and heart rate (BPV; HRV) were assessed over a range of frequencies: very-low frequency (VLF: 0.02-0.2 Hz), low frequency (LF: 0.2-0.6 Hz), high frequency (HF: 0.6-3 Hz), normalized (n)LF, nHF, ratio LF/HF of HRV (LF/HF_(HRV)), and total power (TP: ≦ 3 Hz). Results showed that the concomitant reciprocal changes of spectral powers existed between frequencies of BPV and HRV to the stressful cooling (i.e. VLF_(BPV) versus VLF_(HRV), LF_(BPV) versus LF_(HRV), and nLF_(BPV) versus nLF_(HRV)) which contribute to the underlying mechanisms of sympathetic efferent influences and myogenic cardiovascular responsiveness. Furthermore, compared with the control vehicle in the stressful cooling, HEX restrained the increase of the pressor, tachycardia and VLF_(BPV), except that VLF_(HRV) was reduced. GUA abolished pressor, however, restrained the increase of the tachycardia, VLF_(BPV) and LF_(BPV). In addition, GUA reversed the downward tendency of nLF_(BPV) into an upward tendency and attenuated both nLF_(HRV) and LF/HF_(HRV). DN was virtually undetectable after HEX management but was apparently noticeable after GUA management. Finally, the increase of plasma NO after cooling was diminished after HEX or GUA management. Taken together, these results substantiate that the spectral changes during stressful cooling are highly relevant to the efferent sympathetic rhythmicity and subsequent NO production.