Noggin is a major extracellular antagonist to bone morphogenetic proteins (BMPs) which binds to BMPs and blocks binding of them to BMP-specific receptors and negatively regulates BMP-induced osteoblastic differentiation. In this study, we investigated the effect of noggin silencing by transfection of small interfering RNA (siRNA) on BMP-induced osteoblastic differentiation in vitro and ectopic bone formation in vivo induced by recombinant human BMP-2 (rhBMP-2). Noggin mRNA expression was up-regulated in response to rhBMP-2 in C2C12 cells, a myoblastic cell line, in dose- and time-dependent fashion as determined by real-time RT-PCR assay. Silencing of noggin expression by transfection of noggin siRNA suppressed BMP-stimulated noggin expression, resulting in acceleration of BMP-induced osteoblastic differentiation. For in vivo noggin silencing, siRNA was injected locally into back muscles and transfected into local cells by electroporation, where rhBMP-2-retaining (5 microg) collagen disks had been surgically placed. The implants were harvested at 2 weeks after surgery from experimental and control group mice and analyzed by radiological and histological methods. As a result, bone mineral content of ossicles ectopically induced by rhBMP-2 was significantly increased by silencing of noggin. Our findings suggest that silencing of noggin enhances the osteoblastic differentiation of BMP-responding cells in vitro and new bone formation induced by rhBMP-2 in vivo by eliminating negative regulation of the effects of BMP. RNA interference might be useful for intensifying the effects of BMP in promoting new bone (callus) formation in repair of damaged bone.
On excision of any soft tissue tumor, surgeons should be aware of the potential risk for erroneous management of malignancy. If not, careless surgery may render the treatment protocol complicated and require excessive additional tissue resection with poor function and prognosis. Appropriate salvage treatment may have a significant role to play after unplanned resection of the sarcoma.
The role of fat in regulation of pancreatic secretion was studied in conscious rats by measuring pancreatic secretion and plasma cholecystokinin (CCK) and secretin responses to intraluminal infusion of fat, protein, or trypsin inhibitor via the duodenum. In rats with pancreatic juice continuously returned to the intestine, intraduodenal infusion of 20% emulsified fat (Liposyn), 10% casein, and 0.4% ovomucoid trypsin inhibitor (OMTI) stimulated equivalent increases of approximately threefold in pancreatic protein output. Proglumide reduced fat-stimulated pancreatic protein secretion by greater than 90% but did not inhibit the response to OMTI. Fat significantly increased plasma CCK from basal levels of 0.5 pM to 2-3 pM, but it was a weaker stimulant of CCK secretion than casein (peak CCK levels greater than 10 pM) or OMTI (peak CCK levels 5-6 pM). Fat significantly stimulated secretin release (21.7 pM) compared with casein (6.8 pM), OMTI (4.4 pM), and NaCl (3.5 pM). The inhibition of fat-stimulated pancreatic secretion by proglumide indicates that the small amounts of CCK released by fat are necessary for a normal pancreatic response, suggesting that this response may be the result of potentiation between secretin and small amounts of CCK.
The purpose was to identify vascular influences on the responsiveness to donepezil chloride. The study included 50 untreated probable Alzheimer’s disease patients with the Modified Hachinski Ischemic Score <4. We assessed baseline cognitive status using the Revised Hasegawa Dementia Scale (HDS-R), Clinical Dementia Rating (CDR) and the clock drawing test (CDT). The response to 5 mg of donepezil was monitored by the CDT for 12 months. Patients were classified as true responders (TR), unchanged (UC) and non-responders according to changes on the CDT in response to treatment. High HDS-R scores, low CDT scores, low CDR and presence of hypertension (HBP) and periventricular hyperintensities (PVH) predicted a TR- or UC-type outcome. Aggravation of executive function by HBP and/or PVH and its improvement by donepezil may have been detected by the CDT.
We examined the acute effects of ginseng extract (GS) administration on arterial plasma levels of glucose, free fatty acids (FFA), lactic acid (LA) and pyruvic acid (PA) in resting rats, and in animals that swam for 30 or 60 minutes. Compared to vehicle-treated (saline) control animals, GS did not significantly alter these parameters at rest. During exercise, GS-treated animals had higher blood glucose levels than control rats, and markedly lower concentrations of circulating LA and PA. Plasma FFA was also lower in the GS-treated animals at 30 minutes of swimming. These results provide evidence that ginsenosides can significantly alter mechanisms of fuel homeostasis during prolonged exercise, presumably by increasing the biochemical capacity of skeletal muscle to oxidize FFA in preference of glucose for cellular energy production.
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