A New Way to Accelerate the Distraction of the Transpalatal Suture in Growing Dogs Using Recombinant Human Bone Morphogenetic Protein-2.

OBJECTIVE: The purpose of this study was to evaluate the administration of recombinant human bone morphogenetic protein-2 (rhBMP-2) on trans-sutural distraction osteogenesis (TSDO) of the transverse palatal suture in growing dogs. STUDY DESIGN: A total of 36 growing dogs were used in this study. The experimental animals were treated with different elastic force and rhBMP-2. The bone regeneration was determined with X-ray, histology, and clinical evaluation. The computed values underwent statistical analyses using analysis of variance. RESULTS: The maxillary complex was most noticeably advanced with an applied elastic force of 600 g (22.4 ± 5.0 mm) and 800 g + rhBMP-2 (24 ± 5.1 mm). Immunohistochemical staining showed that the expression of bone morphogenetic protein-2 and bone morphogenetic protein-4 varied with different elastic force. These changes were statistically significant when 600 g and 800 g + rhBMP-2 were applied within 2 weeks of distraction when compared with controls (P < .05). CONCLUSIONS: The results of this study suggest that TSDO in the growing dog should be safe and well tolerated when inducing bony lengthening of the maxilla. rhBMP-2 plays an important role in bone regeneration using TSDO.

Transsutural distraction and tissue regeneration of the midfacial skeleton: experimental studies in growing dogs.

Objective : The purpose of this study was to evaluate the effect of different mechanical forces on the expansion of the palatine suture using transsutural distraction osteogenesis. Methods : A total of 48 dogs were used in this study. The experimental groups were treated with a custom-designed internal distractor. Bone regeneration was determined with x-rays and histology. The computed values underwent statistical analyses using analysis of variance. Results : The maxillary complex was most noticeably advanced with an applied mechanical force of 600 g (20.15 ± 1.36 mm), compared with forces of 400 g (19.88 ± 1.41 mm) and 800 g (2.24 ± 0.93 mm). Immunohistochemical staining showed that the expression of bone morphogenetic protein-2 and bone morphogenetic protein-4 fluctuated with different mechanical forces. These changes were statistically significant when 600 g of force was applied within 30 days of distraction (P < .05). Conclusions : Transsutural distraction osteogenesis in the growing dog should be safe and well tolerated in inducing bony lengthening of the maxilla, and the optimal force is 600 × g. Bone morphogenetic protein-2 and bone morphogenetic protein-4 may play an important roles in the signaling pathways that link mechanical forces and biological responses.

Relative expression of genes involved in artemisinin biosynthesis and artemisinin accumulation in different tissues of Artemisia annua / 中国中药杂志

<p><b>OBJECTIVE</b>To study the relative expression of the genes involved in artemisinin biosynthesis in different tissues including roots, stems, leaves and flowers of Artemisia annua, and establish the relationship between gene expression and artemisinin accumulation, eventually leading to discover the mainly effective genes involved in artemisinin biosynthesis.</p><p><b>METHOD</b>The 7 functional genes involved in artemisinin biosynthesis were detected at the level of expression by using qRT-PCR, and simultaneously the content of artemisinin in the 4 investigated tissues was detected in parallel.</p><p><b>RESULT</b>The 3 genes including HMGR, DXR and FPS which were involved in the upstream pathway of artemisinin biosynthesis showed the highest expression levels in flowers, and the 4 functional genes including ADS, CYP71AV1, CPR and AAR which were involved in the artemisinin-specific biosynthetic pathway were found to be expressed in all the 4 detected tissues. The highest expression level of ADS was found in leaves, then followed by flowers, and the lowest expression level of ADS was found in roots and stems. CYP71AV1 had highest expression level in flowers and lowest in leaves. CPR showed highest expression level in flowers, and AAR had lower expression levels in the other 3 artemisinin-specific pathway genes in all the tissues. The highest content of artemisinin was found in leaves (0.343 mg x g(-1)), then followed by flowers (0.152 mg x g(-1)), roots (0.062 mg x g(-1)) and stems (0.060 mg x g(-1)).</p><p><b>CONCLUSION</b>In the biosynthesis of artemisinin, the upstream genes including HMGR from the MVA pathway, DXR from the MEP pathway and the checkpoint gene FPS were much more active in flowers, and this suggested that flowers might be the tissues of artemisinin precursor biosynthesis, and further DXR contributed more to artemisinin biosynthesis. The positive correlation of ADS expression and artemisinin content in tissues demonstrated that ADS played a very important role in artemisinin biosynthesis, which was the ideal target for engineering the artemisinin biosynthetic pathway. In summary, the functional genes involved in artemisinin biosynthesis do not express at the same level but synergistically.</p>

The effect of bone morphogenetic protein-2 and osteoprotegerin in trans-sutural distraction osteogenesis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To determine if locally administered bone morphogenetic protein-2 (BMP-2) and osteoprotegerin (OPG) improved osteogenesis and new bone formation by trans-sutural distraction osteogenesis.</p><p><b>METHODS</b>Twenty four dogs were divided into three groups randomly and received new internal trans-sutural distraction osteogenesis treatment. Five days after operation, infusion apparatus with double-tube was inserted to submucosa near the distracted zone to deliver controlled release agent of recombinant human bone morphogenetic protein-2/poly (lactic-co-glycolic acid)/fibrin sealant (rhBMP-2/PLGA/FS) in group A and group C. Recombinant human osteoprotegerin/fibrin sealant (rhOPG/ FS) was injected three weeks later in group B and group C. Histology staining and bone histomorphometry were used to measure the changes of maxillary bone sutura after distraction for 1, 2, 4 and 6 weeks.</p><p><b>RESULTS</b>New bone formation observed in distracted zone showed a significant increase in group A and C. Transmission electron microscope showed the osteoblast and osteocyte were active with dilated rough endoplasmic reticulum and a large number of chondriosomes and Golgi complex. After distraction for 6 weeks, indexes of osteoblast of group A, B, and C were 38.5 +/- 7.7, 35.7 +/- 6.5, and 41.7 +/- 11.0, indexes of osteoclast (Ioc) were 5.9 +/- 1.0, 1.2 +/- 0.3, and 2.8 +/- 0.4, bone trabecula thicknesses were (38.36 +/- 13.28), (66.20 +/- 9.16), and (51.85 +/- 9.92) microm respectively. Increased bone density and decreased Ioc were found in group B and C.</p><p><b>CONCLUSION</b>The new elastic distractor is effective in inducing new bone formation. BMP-2 and OPG combination acts synergistically, and leads to significant enhancement of bone formation and remodeling.</p>

Ca~(2+)/calmodulin-dependent kinaseⅡare involved in tumor necrosis factor α-induced cardiomyocyte hypertrophy in rats / 中国药理学通报

Aim To investigate whether Ca~(2+)/calmodulin-dependent kinase Ⅱ(CaMKⅡ)contribute to tumor necrosis factor α(TNF-α)-induced cardiomyocyte hypertrophy.Methods The protein content was assayed with Lowry's method.The cardiomyocytes volumes were measured by computer photograph analysis system.The protein synthesis was assayed with[~3H]-lencine incorporation method.[Ca~(2+)]_i transient was measured by Till image system by cell-loading Fura-2/AM.The expression of CaMKⅡδ_B was determined by Western blot.Results ① TNF-α significantly induced the increase of protein content, [~3H]-leucine incorporation and cell size;These responses were significantly suppressed by KN93, a selective CaMKⅡ inhibitor.② TNF-α increased the amplitude of the spontaneous Ca~(2+) transients in cultured ventricular myocytes from the neonatal rat;CaMKⅡ inhibitor KN93 can suppress the elevation induced by TNF-α.③ TNF-α significantly increased the expression of CaMKⅡδ_B.Concluslon CaMKⅡ signal pathway are involved in TNF-α-induced cardiomyocyte hypertrophy in rats.

Accelerating effects of high glucose on NE-induced cardiac hypertrophy of the cultured myocardial cells / 中国药理学通报

AIM To study the effects of high glucose on the cardiac hypertrophy,cultured cardiomyocytes were used to study the accelerating effects of high glucose on norepinephrine(NE) induced cardiac hypertrophy. METHODS Using cultured myocardial cells as a model, the cellular hypertrophy was observed. The protein content was assayed with Lowrys method. The cardiomyocytes' volumes was measured by computer photograph analysis system. The protein synthesis was assayed with leucine intake method. RESULTS The total cellular protein content?cellular volumes?cellular protein synthesis showed an increase in high glucose group, NE group, high glucose and NE group compared with control group, respectively. High glucose and NE group showed a further increase compared with NE group. CONCLUSIONS The high glucose itself induced hypertrophy of the cultured myocardial cells slightly. Meanwhile high glucose can further accelerate hypertrophy of the cultured myocardial cells induced with NE. The effective mechanism between high glucose and NE on cardiac hypertrophy need further study.

Ca~(2+)/calmodulin-dependent kinaseⅡare involved in tumor necrosis factor ?-induced cardiomyocyte hypertrophy in rats / 中国药理学通报

Aim To investigate whether Ca2+/calmodulin-dependent kinase Ⅱ(CaMKⅡ)contribute to tumor necrosis factor ?(TNF-?)-induced cardiomyocyte hypertrophy.Methods The protein content was assayed with Lowry's method.The cardiomyocytes volumes were measured by computer photograph analysis system.The protein synthesis was assayed with[3H]-lencine incorporation method.[Ca2+]i transient was measured by Till image system by cell-loading Fura-2/AM.The expression of CaMKⅡ?B was determined by Western blot.Results ① TNF-? significantly induced the increase of protein content,[3H]-leucine incorporation and cell size;These responses were significantly suppressed by KN93,a selective CaMKⅡ inhibitor.② TNF-? increased the amplitude of the spontaneous Ca2+ transients in cultured ventricular myocytes from the neonatal rat;CaMKⅡ inhibitor KN93 can suppress the elevation induced by TNF-?.③ TNF-? significantly increased the expression of CaMKⅡ?B.Concluslon CaMKⅡ signal pathway are involved in TNF-?-induced cardiomyocyte hypertrophy in rats.