Chromosome Disorders ; Chromosomes, Human, Pair 13 ; Humans ; Infant ; Male ; Trisomy ; Trisomy 13 Syndrome

Adult ; Asian Continental Ancestry Group ; genetics ; Female ; Humans ; Long QT Syndrome ; genetics ; Mutation, Missense ; Pedigree

Acute Kidney Injury ; chemically induced ; enzymology ; Animals ; Disease Models, Animal ; Gentamicins ; Peptidyl-Dipeptidase A ; metabolism ; Rats

Animals ; Antibiotics, Antineoplastic ; pharmacology ; Blotting, Northern ; Cells, Cultured ; Dexamethasone ; pharmacology ; Doxorubicin ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Regulation ; drug effects ; Glucocorticoids ; pharmacology ; Kidney Glomerulus ; cytology ; drug effects ; metabolism ; Mice ; RNA, Messenger ; drug effects ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

Background Vancomycin has been increasingly recommended for the management of endophthalmitis,but few research report has been published about the pharmacokinetics of intravitreal vancomycin up to now.It is necessary to have an exact method to measure the concentration of vancomyein in animal eyes after intravitreal injection.Objective This study was to observe and compare the phamacokinetical process of vancomycin in serum,vitreous and aqueous humor between normal and infected rabbit eyes.Methods Seventy-two healthy adult rabbits were randomly divided into normal group and infected group and 36 rabbits for each.The animal models of endophthalmitis were established by intravitreal inoculation of 2000 CFU/ml staphylococcus aureus in the right eyes of rabbits in the infected group.Once endophthalmitis developed,0.1 ml vancomycin ( 10 g/L) solution was injected into the vitreous of every rabbit.The peripheral blood,vitreous and aqueous humor samples were respectively collected in 4 rabbits for each group at 0.5,2,4,6,12,24,48,72 and 84 hours after injection for detection of vancomycin concentration by high performance liquid chromatography(HPLC-UV).3p97 software was used to create fit parameters of pharmacokinetics.This experiment followed the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission (Version 1988).Results The accuracy of HPLC fitted the detecting request of biological specimen.The concentration-time data of vancomycin in normal rabbit aqueous humor and vitreous was subject to two-compartment model.The pharmacokinetic parameters were separately as following:Cmax was 50.16 mg/L and 751.42 mg/L,t1/2was 51.04 hours and 53.21 hours.The concentration-time data of vancomycin in infected rabbit aqueous humor and vitreous was subject to one-compartment model.The pharmacokinetic parameters were separately as following:Cmaxwas 24.94 mg/L and 687.66 mg/L,t1/2was 11.42 hours and 12.91 hours.The concentration of vancomycin in serum was much lower and almost undectable.The concentration of vancomycin in vitreous was gradually reduced as the prolong of time after injection in both normal group and infected group,but a obvious decline after increased level was scen in aqueous humor.Compared with normal group,the concentrations of vancomycin in both vitreous and aqueous humor were reduced at various time points(P＜0.05,P＜0.01 ).Conclusions HPLC is simple,highly sensitive and specific for the pharmacokinetic analysis of vancomycon.These results indicate that pharmacokinetic parameters of vancomycin alter in pathological condition,which is helpful for us to establish the better treatment guidelines for endophthalmitis.

Background Research demonstrated that mitochondrial pathway plays a key role in cell apoptosis.Purendan supermicropowder(PRD),a traditional Chinese medicine,may be a potentially effective therapy for neuron apoptosis in diabetic retina.Objective This study was carried out to investigate the effects of PRD on aldose reductase(AR)activity,neuron apoptosis and mitochondrial pathway in retina of diabetic rat.Methods Thirty-six clean male Wistar rats were randomly divided into normal control group,diabetes model group,PRD treatment group randomly and 12 rats for each group.The diabetes models were established by intraperitoneal injection of 25 mg/(kg · d)streptozotocin(STZ)for 3 consecutive days,and blood glucose ≥ 16.7 mmol/L was taken as the standard.PRD solution of 1.8 g/(kg · d)was lavaged in 12 models for 3 months.The eyeballs were enucleated for the preparation of retinal tissue homogenate and slice.AR activity in the retina was detected by ultraviolet spectrophotometry,and neuron apoptosis in retina was assayed by TUNEL staining.Western blot was used to assess the expressions of bcl-2,bax,cyt-c and caspase-3 protein in the retina.The use of animals followed the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Committee(Version 1988).Results Statistically significant differences were found in AR activity and AI among the normal control group,diabetic group and PRD groups(F=90.115,165.540,P＜0.01),and those of diabetic group were evidently higher than the normal control group and PRD group(P＜0.01,P＜0.01).The positive TUNEL cells mainly located in inner nuclear layer and retinal ganglion cell layer.The expressions of bax,cyt-c,caspase-3,bcl-2 and bcl-2/bax in retina were obviously different among these three groups(F =51.332,41.262,25.888,38.564,47.870,P＜0.01),and the expression of bax,cyt-c and caspase-3 protein in diabetic group evidently elevated in comparison with the normal control group and PRD group(t ＝ 10.32,11.04,6.91,P ＜ 0.01)and the expressions of bcl-2 protein and bcl-2/bax value were significantly lower in diabetic rats than in the normal control rats(t =18.05,12.23,P＜0.01).AR activity by AI of retina,the expressions of bax,cyt-c and caspase-3 proteins in retina were obviously lower in PRD group than in diabetes model rats(P ＜ 0.01),and the expression of bcl-2 protein and bcl-2/bax value were significantly higher in PRD group than in diabetes group(P＜0.01).Conclusions PRD can protect retina against the damage caused by high glucose by suppressing AR activity by downregulating the expressions of bax,cyt-c,caspase-3 proteins,increasing the expressions of bcl-2 protein in retina of diabetic rats and further inhibiting the mitochondrial pathway and reducing cell apoptosis in retina of diabetic rats.

Anesthesia, General ; Animals ; Central Venous Pressure ; physiology ; Heart Function Tests ; Hemodynamics ; physiology ; Respiration, Artificial ; Shock, Septic ; pathology ; Swine ; physiology ; Venae Cavae ; physiology

OBJECTIVETo study the relationship between cartilage end-plate calcification (CEC) and cervical intervertebral discs regression (CIDR) in rabbits, and to study the inhibitory effect of combined therapy of Kanggu Zengsheng Capsule (KZC) ansforming growth factor-apsule (TGF-PLC) and igene therapy (GT) on CEC by measuring the thickness of CEC layer.

METHODSThirty-five New Zeland rabbits of 4 months old were selected to establish cervical dynamic imbalance rabbit model for inducing CIDR (No disposal was given to rabbits in the normal control group). Seven months after operation, combined therapy of KZC and PLC were given, in doses calculated by body weight, to the modeled rabbits in the drug treated group with CEC of either superficial layer or full layer, twice a dantly by gavage for 30 successive days. While to those in the gene therapy group, the recombinant plasmid DNA with transforming growth factor-beta1 (TGF-beta1) was injected once their intervertebral discs (ID) of C(2-3) C(3-4) and C(4-5), 20 microl for each injection. One month later, all rabbits were sacrificed with periotic venous gas embolic method and their ID of C(4-5) (including partial body of the upper and lower vertebrae) was resected. The degree of CIDR was evaluated morphologically, and the thickness of CEC in rabbits was measured and compared between groups.

RESULTSThickness of CEC in the model group, either of superficial layer or of full layer, was significantly more than that in the normal control group with significant difference. Both combined KZC and PLC therapy and gene therapy showed significant inhibitory effects on CEC in treating CIDR (P < 0.05).

CONCLUSIONCEC is the initial factor of CIDR with highly positive correlation. Both combined therapy of KZC and PLC and gene therapy can significantly inhibit CEC.

Animals ; Calcinosis ; complications ; pathology ; Cartilage ; pathology ; Cervical Vertebrae ; pathology ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Genetic Therapy ; Intervertebral Disc ; pathology ; Male ; Phytotherapy ; Rabbits ; Random Allocation ; Spinal Diseases ; complications ; pathology ; therapy

The fruit of Pandanus tectorius (PTF) has a long history of use as a folk medicine to treat hyperlipidemia in Hainan province, South China. Our previous studies have shown that the n-butanol extract of PTF is rich in caffeoylquinic acids and has an adequate therapeutic effect on dyslipidemic animals induced by high-fat diet. In this work, seven caffeoylquinic acids isolated from PTF were screened for the lipid-lowering activity in HepG2 hepatoma cells. Oil-Red O staining, microscopy and intracellular triglyceride (TG) and total cholesterol (TC) quantification showed that 3-O-caffeoylquinic acid (3-CQA), 3, 5-di-O-caffeoylquinic acid (3,5-CQA), and 3,4,5-tri-O-caffeoylquinic acid (3,4,5-CQA) significantly inhibited lipid accumulation induced by oleic acid and decreased intracellular levels of TC and TG in a dose-dependent manner. These three caffeoylquinic acids showed no significant cytotoxicity at concentrations of 1 -50 μmol x L(-1) as determined by MTT assay. Realtime quantitative PCR revealed that 3-CQA and 3, 5-CQA significantly increased the expression of lipid oxidation-related genes PPARα, CPT-1 and ACOX1 while 3-CQA, 3, 5-CQA and 3,4,5-CQA decreased the expression of lipogenic genes SREBP-1c, SREBP-2, HMGR, ACC, FAS. Overall, 3-CQA, 3, 5-CQA and 3, 4, 5-CQA may be the principal hypolipidemic components in PTF which can decrease intracellular lipid accumulation through up-regulating the expression of lipid oxidative genes and down-regulating the expression of lipogenic genes.
Carcinoma, Hepatocellular ; metabolism ; China ; Cholesterol ; metabolism ; Gene Expression Regulation ; Hep G2 Cells ; Humans ; Lipid Metabolism ; Liver Neoplasms ; metabolism ; Oleic Acid ; Pandanaceae ; chemistry ; Quinic Acid ; analogs & derivatives ; chemistry ; Sterol Regulatory Element Binding Protein 1 ; Triglycerides ; metabolism

Objective To explore the effects of surface modification of PLGA-[ASP-PEG] scaffold with typeⅠcollagen on the adhesion,proliferation and osteogenic differentiation of rabbit bone marrow stromal cells (BMSCs).Methods After PLGA-[ASP-PEG] materials were modified with typeⅠcollagen chemically,the collagen was coated onto the materials physically.The BMSCs obtained from rabbits were cultured on the modified PLGA-[ ASP-PEG] and on the unmodified PLGA-[ ASP-PEG] as control.The adhesion and proliferation behavior of the cells was analyzed and the expressions of osteogenie marker alkaline phosphatase,osteocalcin,osteopontin,typeⅠcollagen and core binding factor al were also detected.Results X-ray photoelectron spectrometry(XPS) confirmed that TypeⅠcollagen was grafted onto the surface of PLGA-[ASP-PEG] successfully and the collagen content on the materials modified chemically and physically was significantly increased.The abilities of adhesion and proliferation and the expressions of osteogenie makers of the BMSCs were significantly greater than those in the control group(P＜0.05).Conclusion Since Type collagen I can improve the biocompatibility of PLGA- [ASP-PEG] scaffold materials,it can be used as a new way to optimize scaffolds in tissue engineering.