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Objective To learn the toxic effects on rats repeatedly exposed to dichloromethane by dermal route at the same dose for 28 days.Methods Seventy two Sprague Dawley rats were divided into six groups:a solvent control group (oliver oil),four exposure groups (0.75,1.5,3.0 and 6.0 g/kg·BW)and a recovery group.Each group included six female and six male rats.The exposure groups were dermal exposed to DCM at 1.5,3.0 and 6.0 g/kg·BW,6 hours/day,5 days/week for four weeks.The recovery group was dermal exposed to 6.0 g/kg BW of DCMduring the same period then recovered for 2 weeks.Clinical signs including body weight and food consumption of each group were observed.After rats were sacrificed,the hematological and serum biochemical parameters were determined.Histopathological examination was performed on selected tissues for all animals.Results The male rats in test groups including four exposure groups and a recovery group,showed decreased body weight gain.Neutrophilia and lymphocytopenia were determined in females of 3.0 and 6.0 g/kg BW groups and males of 1.5,3.0 and 6.0 g/kg BW groups by blood routine test (P <0.05).The mean levels of serum ALT and AST significantly increased in males of 3.0 and 6.0 g/kg BW groups (P <0.05).Only the mean level of serum TG in males of 6.0 g/kg BW group decreased (P <0.05).No significant differences of these indexes were shown in female rats of all exposure groups compared to control group.The exposure -related significant increases on the incidences of epidermis and dermis lesion,hepatocellular degeneration and necrosis were observed in test groups compared to the control group.The rats of recovery group were exhibited normal percentages of lymphocytes and neutrophils,levels of ALT,AST and TG. The skin and hepatocellular lesion were improved to some extent, but not recovered exactly.Conclusion In a 4 -week repeated -dose toxic study,DCM induce dose -related effects in rats involving skin lesion and liver injury with adverse changes in body weight gain of male rats,part parameters of hematology and serum biochemistry .
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Objective To examine the mutagenicity and antioxidant activity of Proanthocyanidin( PC). Methods Three mutagenicity tests including Ames test,bone marrow micronucleus test and sperm malformation test in mice were conducted. According to the level of erythrocyte MDA,11-month-old rats were randomly divided into five groups including blank control,solvent control and 41. 67,83. 33,250. 0 mg/kg test groups. The content of erythrocyte MDA,SOD and GSH-PX activity of each dosage group were then observed after administration of PC to test the antioxidant activity. Results In all three mutagenicity tests,no mutagenic effect was observed in any PC - treated group. Compared with two control groups,the content of erythrocyte MDA was significantly decreased in 83. 33 and 250. 0 mg/kg groups(both P<0. 05) and GSH-Px activity was significantly increased in 250 mg/kg group(P<0. 05). Conclusion PC had no mutagenic effect but showed antioxidant activity under our experimental conditions.
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<p><b>OBJECTIVE</b>To investigate the effect of sumoylation of alpha-synuclein by SUMO-1 on the mitochondria subcellular localization of alpha-synuclein and its degradation via ubiquitin-proteasome system.</p><p><b>METHODS</b>Primers of wild-type, A53T pathogenic mutant and K96R mutant of human alpha-synuclein were designed to amplify the corresponding cDNAs without stop codon. The cDNAs were cloned into pGEM T-easy vector, analyzed by using enzyme mapping and DNA sequencing, and subcloned into pEGFP-N1 vector. The recombinant plasmids of pEGFP-alpha-synuclein-WT, pEGFP-alpha-synuclein-A53T and pEGFP-alpha-synuclein-K96R were transfected into HEK293 cells by lipofectamine method. The expression of the alpha-synuclein protein was measured by immunofluorescence and confocal microscope. Then mitochondria staining as well as immunofluorescence were utilized to investigate the effect of wild-type, A53T mutant and sumoylation of alpha-synuclein on mitochondria subcellular localization of alpha-synuclein. The effect of sumoylation of alpha-synuclein on its degradation via the ubiquitin-proteasome system in the cells was assayed by Western-blot.</p><p><b>RESULTS</b>The enzyme mapping suggested that the eukaryotic expression plasmids for human wild-type, A53T and K96R mutants of the alpha-synuclein gene were constructed successfully. By immunofluorescence and confocal microscope, it was observed that alpha-synuclein-WT and alpha-synuclein-A53T proteins aggregated in cytoplasm, and alpha-synuclein-K96R protein aggregation was decreased in cytoplasm of cultured cells. The alpha-synuclein proteins of wild-type, A53T and K96R mutants were co-localized with mitochondria. Western-blot analysis revealed that both wild-type and A53T mutant affected the amount of the ubiquitinated proteins.</p><p><b>CONCLUSION</b>Neither overexpression of wild-type and A53T pathogenic mutant alpha-synuclein, nor sumoylation of alpha-synuclein, affected the subcellular localization in the mitochondria. However, overexpression of wild-type and A53T mutant alpha-synuclein affected the amount of the ubiquitinated proteins.</p>
Subject(s)
Humans , Blotting, Western , Cell Line , Mitochondria , Metabolism , Proteasome Endopeptidase Complex , Metabolism , SUMO-1 Protein , Metabolism , Ubiquitin , Metabolism , alpha-Synuclein , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of Astragalus membranaceus (AM) on insulin-like growth factor 1 (IGF-1) expression in a rat model of olivo-cerebellar degeneration and assess the neuroprotective actions of AM meanwhile.</p><p><b>METHOD</b>Rats model of olivo-cerebellar degeneration was established by using 3-acetylpyridine. The effect of AM on the expression of Calbindin D-28K in inferior olive (IO) neurons by immunohistochemistry, the serum IGF-1 level by Elisa, the IGF-1 mRNA level in the cerebellum by RT-PCR were detected respectively.</p><p><b>RESULT</b>AM effectively improve the serum IGF-1 level, Cerebellar IGF-1 mRNA level and the survival of the 10 neurons in a rat model of olivo-cerebellar degeneration, even at a lower dose (9 g x kg(-1)), and the effect was in a dose-dependent manner.</p><p><b>CONCLUSION</b>AM could effectively upregulate the IGF-1 expression in the rat model of olivo-cerebellar degeneration, and have neuroprotective effect on IO neurons.</p>
Subject(s)
Animals , Male , Rats , Astragalus propinquus , Chemistry , Calbindins , Cerebellum , Metabolism , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Pharmacology , Enzyme-Linked Immunosorbent Assay , Gene Expression , Immunohistochemistry , Insulin-Like Growth Factor I , Genetics , Motor Activity , Neuroprotective Agents , Pharmacology , Olivary Nucleus , Metabolism , Plants, Medicinal , Chemistry , Pyridines , RNA, Messenger , Genetics , Random Allocation , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , S100 Calcium Binding Protein G , Metabolism , Spinocerebellar Degenerations , Blood , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To identify the relationship between the expression of BMP/Smads in condylar cartilage and condylar growth modifications in rabbits during mandibular forward positioning.</p><p><b>METHODS</b>Sixty male rabbits with 8 weeks of age were randomly divided into the experimental group (n=36) and control group (n=24). The mandibles of rabbits in the experimental groups were induced to forward position by a functional appliance. The rabbits in the experimental group and control group were sacrificed after 3 days and 1, 2, 4, 8, 12 weeks, respectively. The expression of BMP-2, Smad1/5, 4 and 6 in condylar cartilage was examined by immunohistochemical staining.</p><p><b>RESULT</b>The expression of BMP-2, Smad1/5, 4 and 6 was mainly found in the chondrocytes from the transitional zone and hypertrophic zone, and was also found in the chondrocytes and osteoblasts of the mineralized zone. Compared with those of the age-matched controls, the positive signals for BMP-2, Smad1/5, 4 and 6 in the experimental animals were stronger at early stage (P<0.05), coinciding with the remodeling in condylar cartilage after functional appliance.</p><p><b>CONCLUSION</b>The expression of BMP-2, Smad1/5, 4 and 6 is associated with the adaptive remodeling of the condylar cartilage after functional appliance.</p>
Subject(s)
Animals , Male , Rabbits , Bone Morphogenetic Protein 2 , Bone Morphogenetic Proteins , Genetics , Cartilage , Metabolism , Chondrocytes , Metabolism , Mandibular Advancement , Methods , Mandibular Condyle , Metabolism , Orthodontic Appliances, Functional , Random Allocation , Signal Transduction , Smad Proteins , Genetics , Stress, Mechanical , Transforming Growth Factor beta , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the clinic outcome and indications of sternocleidomastoid (SCM) myocutaneous flap for reconstruction after resection of carcinoma in floor of mouth.</p><p><b>METHODS</b>Thirty-two patients underwent SCM myocutaneous flap for reconstruction of the floor of mouth were reviewed. According to the clinical data and the follow-up, the appearance and function were analyzed.</p><p><b>RESULTS</b>Only one myocutaneous flap was partial necrosis in termination of the flap, and growth with granular. In eight cases, partial epidermal loss over the skin paddle occurred with secondary healing with mucosal epithelium. All patients had oral diet with good separation of the oral floor and the tongue, and had no difficulty in speech intelligibility. The patients' appearance, function and the overall quality of life were improved.</p><p><b>CONCLUSION</b>The SCM myocutaneous flap appears to be easy to use and suitable for reconstruction of the defect after resection of oral floor carcinoma, the indications of this flap should be selected carefully.</p>