AIM: Currently available anti-scarring regimens for glaucoma filtration surgery have potentially blinding complications and safer alternatives would be beneficial. This experiment is to investigate the effect of TGF-β2 antisense oligodeoxynucleotide on differentiation, proliferation of subconjunctival fibroblast following glaucoma filtration surgery.METHODS: Glaucoma filtration surgery were performed on both eyes of 28 rabbits. TGF-β2 antisense oligodeoxynudeotide was subconjunctivally injected in the right eyes (A group), and TGF-β2 missense oligodeoxynucleotide (B group)or PBS(C group) was used at the same method in the left eyes as controls. Rabbits were killed at 4,7,14 and 28 days after surgery. Intraocular pressure (IOP), bleb characteristics were recorded at different time point. Subconjunctival fibroblasts were examined by immunohistochemistry and electron microscopy.RESULTS: The IOP of rabbits in group A was significantly lower at 14 days (6.74± 1.18 mmHg) and 21 days (8.15± 1.97mmHg) after operation than the IOP in group B (8.53± 1.04,9.72± 1.09 mmHg)(P ＜0.01) and group C(8.79± 1.21, 9.43±1.27 mmHg) (P ＜0.05). The mean bleb survival time was longer (17.2 days) in group A than that of group B (14.5 days) and group C (13.5 days)(P＜0.05). The population of the cells expressing α -smooth muscle actin(α -SMA) and proliferating cell nuclear antigen (PCNA) was significantly reduced in group A compared with the group B and C. The ultrastructure of fibroblast was not altered by TGF-β2 anti-sense oligodeoxynucleotide.CONCLUSION:TGF-β2 antisense oligodeoxynucleotide can prevent the scar formation after glaucoma surgery by inhibit the differentiation and proliferation of subconjunctival fibroblast. It could be a potentially useful anti-scarring alternative for the prevention of late surgical failure.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Cyclophosphamide ; therapeutic use ; Dexamethasone ; therapeutic use ; Disease-Free Survival ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; L-Lactate Dehydrogenase ; blood ; Lymphoma, T-Cell ; blood ; drug therapy ; therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Remission Induction ; Retrospective Studies ; Survival Rate ; Transplantation, Autologous ; Vincristine ; therapeutic use ; Young Adult

· AIM: To investigate the influence of TGF-β 2 antisense oligonucleotide(ASON) on the differentiation, proliferation of stromal fibroblast in corneal stroma injury.both eyes of 28 rabbits, the right eyes were served as experimental group, corneal incisions were sutured with 8-0 coated vicryl suture carrying TGF-β 2 ASON; the left eyes were served as control group, corneal incision were sutured with common 8-0 coated vicryl suture. Rabbits were killed at 4, 7, 14 and 28d after surgery, stromal fibroblasts were examined by immune histochemistry and electron microscopy.significantly reduced the numbers of cells expressingα -smooth muscle actin (α -SMA) and proliferating cell nuclear antigen (PCNA). The ultrastructure of fibroblast had no significant difference in two groups.differentiation and proliferation of stromal fibroblast in corneal injury. This will be a new method to adjust corneal wound repair.

39℃)developed at the progressive stage of this disease.Physical examination showed variously sized,round or oval,atrophic and variola-like scars along with scattered erythematous patches,papules, necrosis and crusts on the face and extremities.The face was edematous,and there were some edematous and erythematous plaques with a necrotic center on the legs and arms.Histological examination revealed a massive infiltration with atypical CD8~+lymphocytes around the vessels and appendages in dermis.A diagnosis of CD8~+cutaneous T-cell lymphoma(CTCL)was made.Glucocorticoid and immunosuppressants were effective in controlling the condition.Up to the time of the writing,there has not been any definite evidence of systemic involvement.

Objective To investigate the influence of factors related to metabolic syndrome(MS)on the outcome in subjects without diabetes mellitus in a community.Methods A two-year follow-up study was conducted in 885 subjects who were enrolled in the epidemiologic survey carried out in Pingliang Community, Shanghai in 2002.Oral glucose tolerance test,lipid prefde,blood pressure(BP),body mass index(BMI),waist and hip circumferences were measured.Results (1)The baseline of BMI,fasting plasma glucose(FPG),2h plasma glucose after glucose loading(2hPG),BP,triglyceride(TG)in the subjects with impaired glucose regulation(IGR)increased significantly as compared to those with normal glucose regulation(NGR)(all P

OBJECTIVETo identify the antithrombin (AT) phenotype and gene mutation of a kindred with hereditary antithrombin deficiency.

METHODSPlasma AT activity and AT antigen level of the propositus and his kindred members were determined with chromogenic substrate method and immunoassay, respectively. All the seven exons and intron-exon boundaries of antithrombin gene were analyzed by PCR and direct sequencing of amplified PCR products from the propositus.

RESULTSThe propositus AT antigen level was normal but his AT activity was only 65% of normal value suggesting that he had type II AT deficiency. A heterozygous G13830A mutation in exon 6 resulting in Arg393His missense mutation in his AT polypeptide was identified in the propositus. The same phenotype and gene mutation were found in other 3 kindred members.

CONCLUSIONThe type II AT deficiency found in this kindred is caused by heterozygous G13830A mutation in AT gene.

Adult ; Antithrombin III ; genetics ; metabolism ; Antithrombin III Deficiency ; genetics ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree

To investigate the effects of 2-(4-methoxycarbonyl-2-tetradecyloxyphenyl)carbamoylbenzoic acid (CX09040) on protecting pancreatic β cells, the β cell dysfunction model mice were induced by injection of alloxan into the caudal vein of ICR mice, and were treated with compound CX09040. Liraglutide was used as the positive control drug. The amount and the size of islets observed in pathological sections were calculated to evaluate the β cell mass; the glucose stimulated insulin secretion (GSIS) test was applied to estimate the β cell secretary function; the oral glucose tolerance test (OGTT) was taken to observe the glucose metabolism in mice; the expressions of protein in pancreas were detected by Western blotting. The effects on the target protein tyrosine phosphatase 1B (PTP1B) were assessed by the PTP1B activities of both recombinant protein and the intracellular enzyme, and by the PTP1B expression in the pancreas of mice, separately. As the results, with the treatment of CX09040 in alloxan-induced β cell dysfunction mice, the islet amount (P<0.05) and size (P<0.05) increased significantly, the changes of serum insulin in GSIS (P<0.01) and the values of acute insulin response (AIR, P<0.01) were enhanced, compared to those in model group; the impaired glucose tolerance was also ameliorated by CX09040 with the decrease of the values of area under curve (AUC, P<0.01). The activation of the signaling pathways related to β cell proliferation was enhanced by increasing the levels of p-Akt/Akt (P<0.01), p-FoxO1/FoxOl (P<0.001) and PDX-1 (P<0.01). The effects of CX09040 on PTP1B were observed by inhibiting the recombinant hPTP1B activity with IC50 value of 2.78x 10(-7) mol.L-1, reducing the intracellular PTP1B activity of 72.8% (P<0.001), suppressing the PTP1B expression (P<0.001) and up-regulating p-IRβ/IRβ (P<0.01) in pancreas of the β cell dysfunction mice, separately. In conclusion, compound CX09040 showed significant protection effects against the dysfunction of β cell of mice by enlarging the pancreatic β cell mass and increasing the glucose-induced insulin secretion; its major mechanism may be the inhibition on target PTP1B and the succedent up-regulation of β cell proliferation.
Alloxan ; Animals ; Benzoates ; pharmacology ; Biological Assay ; Disease Models, Animal ; Glucose ; metabolism ; Glucose Tolerance Test ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; Liraglutide ; pharmacology ; Mice ; Mice, Inbred ICR ; Molecular Weight ; Pancreas ; drug effects ; enzymology ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; antagonists & inhibitors ; Signal Transduction

OBJECTIVETo compare the results of observed individual means (OIM) model with beta binomial-normal (BBN) model and to apply the two models to assessment of long-term dietary lead exposure.

METHODSFood consumption data were obtained from the National Nutrition and Health Survey conducted in 2002 by 24-hour recall method. Contamination data were derived from the national food contamination monitoring program from 2000 to 2006 and from monitoring data of Customs exports for agricultural products between 2005 and 2006. By multiplying the average consumption of food with the average concentration of contaminant, the OIM model calculated dietary intake per day. By correcting the within-person variation and keeping the between-person variation, the BBN model built dietary intake in the long-term.Using the example of food lead data, the results of two models were compared.

RESULTSThe high-end percentile of OIM model was higher than the BBN model in various age groups.In the general population, the dietary intake of OIM model from 25th percentile to 99.9th percentile was between 1.167 and 7.313 µg×kg(-1)×d(-1), and the dietary intake of BBN model with the same percentile range was between 1.193 and 5.729 µg×kg(-1)×d(-1). The median of various groups was similar between the two models. The dietary intakes in the general population of two models were 1.543 and 1.579 µg×kg(-1)×d(-1).

CONCLUSIONThe high-end percentile of OIM model is more conservative than BBN model in the long-term dietary exposure assessment.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Food Contamination ; Humans ; Lead ; Lead Poisoning ; epidemiology ; Male ; Middle Aged ; Models, Statistical ; Risk Assessment ; methods ; Young Adult

OBJECTIVETo observe the changes in Aβ40, Aβ42 and ADDLs in brains of 3 month-old APPswe/PS1dE9 double transgenic mice after six-month intervention with curcumin, in order to discuss the neuroprotective effect of curcumin.

METHODAPPswe/PS1dE9dtg mice were randomly divided into the model group, the Rosiglitazone group (10 mg x kg(-1) x d(-1)) and curcumin high (400 mg x kg9-1) x d(-1)), medium (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dosage groups, with C57/BL6J mice of the same age and the same background in the normal control group. After 6 months, the immunohistochemical staining (IHC) and the Western blot method were used to observe the changes in positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area, their distribution and protein expressions.

RESULTBoth of the immunohistochemical staining and the Western blot method showed more positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area and higher protein expressions in the model group than the normal group (P < 0.01). IHC showed a lower result in the Rosiglitazone group than the model group (P < 0.05), while Western blot showed a much lower result (P < 0.01). The number of Aβ40, Aβ42 and ADDLs positive cells and the protein expressions decreased in the curcumin high group, the medium group showed a significant decrease (P < 0.01), and the low dose group also showed reductions in the protein expressions of Aβ40 and Aβ42.

CONCLUSIONThe six-month intervention with curcumin can significantly reduce the expressions of hippocampal Aβ40, Aβ42 and ADDLs in brains of APPswe/PS1dE9 double transgenic mice. Whether curcumin can impact Aβ cascade reaction by down-regulating expressions of Aβ40, Aβ42 and ADDLs and show the neuroprotective effect needs further studies.

Alzheimer Disease ; drug therapy ; genetics ; metabolism ; Amyloid beta-Peptides ; genetics ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Curcumin ; administration & dosage ; Disease Models, Animal ; Hippocampus ; drug effects ; metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuroprotective Agents ; administration & dosage ; Plant Extracts ; administration & dosage

Long-tem culture initiating cells(LTC-IC), and in vitro assay of hematopoietic stem/progenitor cells, still represent a heterogeneous population in terms of proliferative capacity and sensitivity to different growth factors. Human umbilical cord (CB) is rich of hematopoietic progenitor cells measured by clonogenic assays and stem cells capable of reconstituting the marrow after transplantation. The influence of culture conditions on the in vitro behavior of LTC-IC from CB was evaluated. First, by using IRES sequence, FL and TPO cDNA were recombined with retroviral vector pLXSN by gene recombination technology. The recombinant plasmid pLFSN, pLTSN, pLFTSN were transfected into human stromal cell line HFCL. Then, LTC-IC were evaluated in long term cultures, comparing five types of stromal feeder layers: human bone marrow stromal cell, human stromal cell line HFCL, and stromal cell lines HDF tranfected with FL gene, HLT transfected with TPO gene or HFT co-transfected with FL and TPO genes. The results were demonstrated that after 8 weeks of coculture, three types of stromal cell lines that supported the maintenance of CFU-C for up to 3 weeks in vitro were identified. However, cocultivation of human bone marrow stromal cell and CB CD34(+) cells on HFT, CFU-C production continued up to 6 weeks or longer on these stroma. The absolute LTC-IC frequency in CD34(+) cells on human bone marrow stromal cell (2.65 +/- 0.76/1 000 cells) was no significant difference with on HFT (3.65 +/- 0.58/1 000 cells). Thus, HFT acts by direct contact to maintain the phenotype and function of the most primitive and quiescent human progenitors. Furthermore, HFT cell line was selected as the optimal one for supporting long-term culture feeder. It was concluded that LTC-IC progenitors from cord blood maintain growing upon the FL/TPO gene-modified stromal feeder layers in vitro.