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PAMAM dendrimer is one of the most widely studied dendrimers in recent years, which has a large number of functional groups on the surface and cavities inside, specific three-dimensional structure and good biocompatibility, permeability and stability. It has been widely applied in drug and gene carrier fields and may become a new absorption enhancer. In order to study the absorption enhancing effects of PAMAM dendrimers, liquiritin was selected as the model drug, with the protection of spleen and liver, detoxification and other functions, but it had not been widely used in clinical application because of its difficult absorption, first pass effect, and low bioavailability. This topic was based on the two main determinants (solubility and permeability) of intestinal absorption in the body, researched the physicochemical properties of liquiritin, analyzed the transport volume of liquiritin with or without PAMAM dendrimers by using Caco-2 cell model, and analyzed the cytotoxicity of PAMAM dendrimers on Caco-2 cells by MTT experiments. These results showed that 0.1% of the G4 generation PAG can promote the absorption of liquiritin safely and effectively, and it was suitable for further development into a new type of pharmaceutical excipients.
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The solubility and permeability on four kinds of flavonoids (kaempferol, hesperidin, apigenin, genistein) were test according to the theory of biopharmaceutics classification system (BCS), and their absorption mechanism. The solubility was investigated by the method in determination of solubility of "Chinese Pharmacopoeia 2010". To detect appearance permeability of compounds mentioned above, the appropriate concentrations were selected by the MTT method in cell transfer experiments in Caco-2 cell model, which established by in vitro cell culture method. Therefore, these compounds were classified with BCS according to solubility and permeability. In addition, to explore absorption mechanisms, the experiments in three different concentrations of compounds in high, medium and low in bidirectional transformation methods in Caco-2 cell model contacted. The study indicated that all of kaempferol, hesperidin, apigenin, genistein have the characteristics in low solubility and high permeability, which belong to BCSⅡ, and the absorption mechanism of kaempferol was active transportation. Whereas, hesperidin, apigenin, genistein were passive transportation. In this study, it carried out initial explorations on establishment of determination for solubility and permeability in flavonoids, and provided theoretical reference for further research on BCS in traditional Chinese medicine.
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Objective To investigate the effects of hyperbaric oxygen (HBO) therapy performed at different times on the cognitive dysfunction of rats with traumatic brain injury. Methods The traumatic brain injured models were established by use of lateral fluid percussion in rats. Ninety-six rats were equally randomized into 4 groups: control group (group A), traumatic brain injured model group (group B), traumatic brain injured model plus conventional therapy group (group C), traumatic brain injured model plus both conventional therapy and HBO therapy group (group D). And group D also divided into 4 subgroups (n=6): D-3 h group, D-12 h group, D-24 h group and D-72 h groups that HBO therapy was performed at 3, 12, 24 and 72 h of the traumatic brain injury, respectively. The changes of learning and memory abilities before or after the therapy in each group were tested by Morris water maze method. Results Group B had the longest latency of finding the underwater platform as compared with the other 3 groups, followed by group C, group D and group A; as to the 4 sub-groups, D-72 h group had the longest latency of finding the underwater platform as compared with the other 3 groups, followed by group D-24 h, group D-12 h and group D-3 h. Group A could cross the original platform in the spatial probe test most often among all the 4 groups, followed by group D, group C and group B; group A, group C and group D was significantly different in clossing the original platform in the spatial probe test as compared with group B (P<0.05); group D-3 h could cross the original platform in the spatial probe test most often among all the 4 sub-groups, followed by group D-12 h, group D-24 h and group D-72 h.Conclusion HBO treatment can effectively improve the cognitive dysfunction of rats with traumatic brain injury, especially those within 12 h of injury.
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Objective To analyze the clinical management, surgical indications and surgical approaches for epidural hematoma straddling the transverse sinus. Methods The clinical data were collected from 58 patients with epidural hematoma straddling the transverse sinus treated between September, 2001 and December, 2007. Of these patients, the hematoma was found by the initial head CT scan in 42 cases; 10 patients had delayed hematoma, and 6 showed delayed hematoma during craniotomy. All the patients were scanned using 16-slice spiral CT for coronal and sagittal three-dimensional reconstruction, and the total hematoma volume and the supratentorial and infratentorial hematoma volumes were calculated. Forty-two patients were found to have the straddling hematoma volume no less than 30 mL or infratentorial hematoma volume over 15 mL. According to the extension of the hemotoma, a bone flap spanning the transverse sinus was taken, and after hematoma removal, the bone flap was reduced and fixed with cranial screws. In 8 patients with other hematomas or severe intracranial hypertension, routine removal of the hematoma or decompressive craniectomy was performed. Results Fifty-four of the patients recovered, 3 were capable of independent living, and 1 sustained severe disabilities after the operations. No death occurred in these patients. Conclusion In patients with epidural hematoma straddling the transverse sinus, conservative treatment can be administered in cases with the straddling hematoma volume < 30 mL or infratentorial hematoma volume < 15 mL, otherwise timely surgical interventions should be performed. One-step preparation of the bone flap spanning the transverse sinus is safe but secure internal fixation is necessitated after reduction of the bone flap.
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Objective To study the changes of cytochrome C (CtyC) and apoptosis-induced factor (AIF) in the brain and effects of them on neuronal cells in rats after traumatic brain injury (TBI). Methods Seventy Sprague-Dawley (SD) rats were randomly divided into sham-injury group (n=10) and brain injury group. The brain injury group was divided into 6 subgroups according to 1, 6, 24, 48, 72, 168 h after traumatic brain injury (n=10). Rat models with contusion and laceration of brain were established by Feeney's impact with flee falling. Fluorescence intensity of CtyC and AIF were observed by immnnofluorescence and confocal laser scanning microscopy at different time points. The effects of CtyC and AIF on neuronal cells were observed by double-labeled immunofluorescence. Results (1)The changes of CtyC in the brain after TBI: at 1, 6, 24 and 48 h following TBL CtyC was 1.89±0.03, 2.69±0.07, 2.99±0.06 and 3.05±0.05 in the cortex and 1.34±0.04, 1.87±0.03, 2.60±0.03 and 2.80±0.06 in the hippocampus, respectively, being significantly higher than that of sham-injury group (P<0.05); at 72 h, CtyC declined to 1.94±0.05 in the cortex and to 1.12±0.04 in the hippocampus, respectively, being significantly higher than that of sham-injury group (P<0.05); at 168 h, CtyC recovered to the normal level in the cortex and hippocampus, being not significantly different between injury group and sham-injury group. (2) The changes of AIF in the brain after TBI: at 1, 6, 24 and 48 h following TBI, AIF was 1.82± 0.16, 2.16±0.34, 2.75±0.22, 2.87±0.12 in the cortex and 1.27±0.06, 2.01±0.05, 2.49±0.02, 2.62±0.05 in the hippocampus, respectively, being significantly higher than that of sham-injury group (P<0.05); at 72h, AIF declined to 1.35±0.09 in the cortex and to 1.32±0.05 in the hippocampus, respectively, being significantly higher than that of sham-in jury group (P<0.05); at 168 h, AIF recovered to the normal level in the cortex and hippocampus, being not significantly different between injury group and sham-injury group (P<0.05). (3) CtyC and AIF triggered neuronal cell apoptosis. Conclusion CtyC and AIF might release from mitochondria after TBI, and can induce neuronal cell apoptosis as apoptosis-inducing factors.
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Objective To investigate the changes in mitoehondrial membrane potential of the rat neurons after acute brain contusion and laceration injuries. Methods Seventy Sprague-Dawley (SD)rats were randomized into the sham injury group(n=10)and brain injury group.The brain injury group was divided into 6 subgroups(n=10)for observation at 1,6,and 24 h and 2,3,and 7 days after acutebrain contusion and laceration injury,which was induced by impact of the brain with a flee-falling object.In the brain slices labeled with fluorescent JC-l staining,the changes in the mitoehondrial membrane potential of the neurons were observed under confocal laser scanning microscopy at the indicated time points.The neuronal apoptosis Was detected using Hoehesd3342 staining and TUNEL assay,and the number of apoptotic neurons was determined under optical microscope.The ultrastructural alterations of the neurons were observed with transmission electron microscopy. Results Compared with that of the sham injury group,the mitoehondrial membrane potential of the neurons decreased significantly 1 h alterthe brain injury(P<0.01),reachingthe lowestlevel at 24 h,and maintained the low level aRerwards.Apoptotie neurons were identified in the brain slices with Hochest33342 staining.One hour after the brain injury,TUNEL assay revealed a small number of positive neurons,which increased significantly at 6 h(P<0.01)and reached the highest level at 48 h.The alteration pattern of the number of the positive neurons showed a 24-h delay in compariSOIl witll that of the mitochondrial membrane potential aRer the brain trauma.Under electronmicroscope.the mitocbondria of the neurons exhibited only slight swelling at l h. and obvious morphological changes of the mitochondria occurred 6 h after the brain trauma,accompanied by chromatin fragmentation,presence of marginal nuclei and broadened nuclear membrane;nuclear condensation and chromatolysis were observed in the neurons 24 h after the brain trauma.Conclusion In rats with acute brain contusion and laceration injuries,the mitochondrial membrane potential of the neurons decreases early(<1h)after the brain injury,which induces apoptosis of the neurons.