Objective To explore the role of tissue inhibitor of metalloproteinase-1(TIMP-1) during renal senescence by using human TIMP-1 transgenic mice.Methods Renal histological changes of wild type mice and transgenic mice at the age of 3,12,24 months were observed by periodic acid-schiff(PAS)staining of paraffin sections.The numbers of F4/80 positive cells were detected by immunofluoreseence.The protein expressions of TIMP-1,TIMP-2,matrix metalloproteinase(MMP)-9,MMP-2,intercellular adhesion molecule-1(ICAM-1),transforming growth factor?1(TGF-?1),collagenⅢand collagenⅣwere detected by Western blot.The activities of gelatinases and TIMP-1 were examined by gelatin zymography and reverse zymography respectively.Results Focal renal fibrosis was found in two genotypes with aging.At the age of 24 months,compared with wild type,in kidneys of transgenic type,the expressions and activities of gelatinases were dowregulated (MMP-2:2.08?0.20 vs.3.39?0.43;MMP-9:4.02?0.82 vs.6.72?1.40,all P＜0.05);the expressions of collagenⅢ,collagenⅣ,ICAM-1,and TGF-?1 were upragulated(0.72+0.11 vs.0.57?0.09;0.84?0.13 vs.0.6?0.11,0.72?0.12 vs.0.53?0.07; 0.69?0.12 vs.0.45?0.09,all P＜0.05),and the numbers of F4/80 positive cells were increased (18.8?4.4 vs.12.7?3.6,P＜0.05)with the upregulated expression and activity of TIMP-1(1.10?0.18 vs.0.62?0.09;50.75?7.25 vs.20.64?3.50,P＜0.05).Conclusions TIMP-1 could promote age-related renal fibrosis through enhancing inflammation reaction by ICAM-1 upregulation.

OBJECTIVETo investigate changes of serum total oxidation status (TOS) and total antioxidant status (TAS) and their association with apolipoprotein (a) [Apo(a)] in patients with polycystic ovary syndrome (PCOS) combined with infertility.

MWTHODSNinety patients with PCOS and infertility were selected as the study group, including 45 patients treated with antioxidants combined with Diane-35(group A) and 45 with Diane-35 therapy only (group B), with 45 healthy volunteers with normal menstruation and normal dual phase basic body temperatures as the control group. Serum TOS of the participants was determined by dual xylenol orange method, and serum TAS was determined with ABTS method; plasma Apo(a) level was determined by dual wavelength immune transmission turbidity method.

RESULTSBefore treatment, serum TOS, OSI, and Apo(a) levels were significantly higher and TAS level was significantly lower in the study group than in the control group (P<0.05). Serum TOS, OSI, and Apo (a) were significantly lowered and TAS was significantly increased in group A after the therapy as compared with the levels before therapy and the levels in group B. The rate of natural recovery of menstruation was significantly higher and the incidence of cardiovascular disease was significantly lower in group A than in group B (P<0.05). Pearson correlation analysis showed that serum TOS and OSI were positively correlated with plasma Apo(a) (r=0.524 and 0.531, P<0.05), and serum TAS was negatively correlated with plasma Apo(a) (r=-0.519, P<0.05).

CONCLUSIONAntioxidant therapy can lower TOS, OSI and Apo(a) levels and increase TAS level to lessen oxidative stress, improve the prognosis, and reduce the risks of cardiovascular disease in patients with PCOS and infertility.

Antioxidants ; metabolism ; Apoprotein(a) ; blood ; Cyproterone Acetate ; therapeutic use ; Drug Combinations ; Ethinyl Estradiol ; therapeutic use ; Female ; Humans ; Infertility, Female ; blood ; Oxidative Stress ; Polycystic Ovary Syndrome ; blood ; drug therapy

Collagen Type I ; analysis ; Collagen Type III ; analysis ; Fluorescent Antibody Technique, Indirect ; Humans ; Liver ; chemistry ; Microscopy, Confocal

In this paper, the five strains of Polygonatum odoratum were used as the experimental materials to test the supercooling point, freezing point, the degree of supercooling, the transition stage time, cooling time and water composition of the plant tissue. The cold resistance of P. odoratum was analyzed with the Gray Correlation Method. The results showed that the cold resistances of the five strains of P. odoratum were different, and the water content of plant tissue had some relevance with freezing point and supercooling point, whereas, it could not be measured when the moisture content was too low. The order of cold resistance of the five strains of P. odoratum was ZJCY, DYYZ, XYYZ, CYYZ and JZ I.
Cold Temperature ; Plant Roots ; chemistry ; physiology ; Polygonatum ; chemistry ; classification ; physiology ; Water ; analysis

BackgroundObstruction of aqueous humor out flow pathway or abnormality of the extracellular matrix( ECM ) of trabecular meshwork cells causes high intraocular pressure. The balance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases(TIMPs) is critical for the metabolism of ECM. Interleukin1α(IL-1α) can influence outflow of aqueous humor by regulating MMPs level. Objective This study was to investigate the effect of interleukin-1α on the expression of MMP-2,MMP-3 and TIMP-I in cultured swine trabecular meshwork cells.Methods Swine sclera with trabecular meshwork tissue was isolated from 20 swine eyes and cultured with explant cultured method. Cultured cells were passaged and third generation cells were identified by fibronectin ( FN ) and laminin ( LN ) staining. After 24 hours of serum starvation, trabecular meshwork cells treated with IL-1α at the concentration of 10 mg/L were regarded as the IL group,and serum-free culture medium used to treat trabecular meshwork cells was regarded as the control group. The expression of MMP-2, MMP-3 and TIMP-1 proteins in trabecular meshwork cells were detected by immunohistochemistry,and the expression of MMP-2 mRNA, MMP-3 mRNA and TIMP-1 mRNA were detected by RT-PCR. The examination results were compared between the two groups. ResultsThe third generation of cells were positive for FN and LM. Compared with the control group, the expression levels of MMP-3 and TIMP-1 proteins(A value) in trabecular meshwork cells were significantly higher in the IL group than the control group(t=-7. 694,t =-5. 199,P＜0. 05) ,but no obvious difference was found in the expression of MMP-2 between the two groups( t=-2. 365, P＞0.05 ). The higher expression levels in MMP-3 mRNA and TIMP-1 mRNA (A value) in trabecular meshwork cells were seen in comparison with the control group (t =-3. 025,t=-1. 921 ,P＜0. 05). However,similar results were found in the expression of MMP-2 mRNA between the two groups(t =- 1. 173, P＞0.05 ). ConclusionsThe overexpression of MMP-3 and TIMP-1 proteins and their mRNA leads to the imbalance of MMP-3/TIMP-1 and promotes the decomposition of ECM in the trabecular meshwork, and therefore increases aqueous outflow.

Drug metabolism studies, including in vivo and in vitro metabolism studies, are significant in the design of candidate compounds and screening of lead compounds at drug discovery/development stages. Compared with in vivo metabolism studies, in vitro metabolism studies have the advantages of rapidity, simplicity, without consumption of large amounts of samples and animals. Moreover, it is convenient for researchers to observe the selective interaction between compound and target. Therefore, in vitro metabolism studies are appropriate for high throughput screening of compounds which are lack of metabolism information and have been widely used during drug discovery stages. This article briefly introduced the application of in vitro drug metabolism studies based on the metabolic stability, reaction phenotyping and metabolic drug-drug interactions, aiming to raise valuable evaluation strategies for innovative drug discovery in China.
Animals ; Cytochrome P-450 Enzyme System ; metabolism ; Drug Design ; Drug Discovery ; methods ; Drug Evaluation, Preclinical ; Drug Interactions ; Drug Stability ; Glucuronosyltransferase ; metabolism ; Humans ; Pharmaceutical Preparations ; metabolism ; Phenotype

OBJECTIVETo observe the therapeutic effect and to explore the best opportunity of acupuncture on spontaneous facial paralysis in acute stage.

METHODSBy prospective cohort study, 80 patients were divided into an observation group (n = 59) and a control group (n = 21). The course of disease was less than 5 days in the observation group and more than 7 days in the control group and had not received acupuncture treatment. They were all treated with acupuncture at Sibai (ST 2), Dicang (ST 4), Jiache (ST 6) and Cuanzhu (BL 2) etc. for 8 weeks. The facial nerve function grading (House-Brackmann, HB) and facial disable index (FDI) before treatment, 8 days after onset, 2, 4, 6, 8 weeks and 3 months after treatment were evaluated.

RESULTSBoth two groups could decrease HB grading and increase FDI score (all P < 0.05), and the observation group was superior to the control group in improvement degree (all P < 0.05). The cured rate of 86.4% (51/59) in the observation group was superior to that of 76.2% (16/21) in the control group, with significant difference between the two groups (P < 0.05). Compared with the control group, the treatment time of cured patients in the observation group was shorter [(25.98 +/- 11.25) days vs (39.31 +/- 13.07) days, P < 0.01], and the incidence of sequelae of 5.1% (3/59) in the observation group was lower than that of 9.5% (2/21) in the control group (P < 0.05).

CONCLUSIONAcupuncture can improve the therapeutic effect, shorten the treatment course and reduce the sequelae incidence of spontaneous facial paralysis in acute stage.

Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Child ; Facial Paralysis ; therapy ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the efficacy and security of anti-platelet and anticoagulant therapy on prevention of ischemic stroke in patients with nonvalvular atrial fibrillation (NAF).

METHODSWe searched PubMed, EMbase, CENTREN and its affiliated clinical trial registration data center, CBMdisc, VIP, and CNKI databases from establishment to Dec 2009 to identify randomized controlled trials (RCTs) covering the use of anti-platelet agents and anticoagulants for patients with NAF. Meta-analysis was performed by using RevMan 5.0 software after the strict evaluation of the methodological quality of the included RCTs.

RESULTSFourteen RCTs involving 15 880 patients were include. Compared with placebo or no use of anti-platelet drugs, antiplatelet therapy didn't reduce ischemic stroke (RR = 0.83, 95%CI 0.68 to 1.00, P = 0.05), systemic emboli (RR = 0.71, 95%CI 0.34 to 1.51, P = 0.38) and all-cause mortality (RR = 0.88, 95%CI 0.73 to 1.07, P = 0.21) while significantly increased the major bleeding (RR = 2.88, 95%CI 1.21 to 6.86, P = 0.02) in patients with NAF, intracranial hemorrhage was not affected by antiplatelet therapy in patients with atrial fibrillation (RR = 3.25, 95%CI 0.84 to 12.62, P = 0.09). Compared with anti-platelet therapy, anticoagulant therapy significantly reduced the incidence of ischemic stroke (RR = 1.84, 95%CI 1.48 to 2.28, P < 0.01) and systemic emboli (RR = 1.94, 95%CI 1.24 to 3.03, P = 0.004) but significantly increased the incidence of intracranial hemorrhage (RR = 0.49, 95%CI 0.31 to 0.78, P = 0.003), did not affect all-cause mortality (RR = 1.06, 95%CI 0.90 to 1.23, P = 0.50) and the incidence of major bleeding (RR = 0.95, 95%CI 0.76 to 1.19, P = 0.66) in NAF patients.

CONCLUSIONSCompared with the placebo and no use of anti-platelet drugs, anti-platelet therapy didn't reduce ischemic stroke and systemic emboli but increased the risk of major bleeding in NAF patients. Compared with anti-platelet therapy, anticoagulant therapy significantly reduced the ischemic stroke and systemic emboli without increasing the risk of major bleeding, but significantly increased the incidence of intracranial hemorrhage in NAF patients. Since the study included RCTs with limited and less uniform outcome endpoints, the conclusions should be verified with RCTs with more uniform endpoints and longer follow-up time.

Anticoagulants ; therapeutic use ; Atrial Fibrillation ; complications ; therapy ; Humans ; Platelet Aggregation Inhibitors ; therapeutic use ; Stroke ; etiology ; therapy ; Treatment Outcome

OBJECTIVETo study the correlation factors of acute paraquat intoxication prognosis.

METHODSThe early paraquat concentration in plasma and urine, leukocyte count, hepatic and renal function, amylase, electrolyte and the parameters of arterial blood gas were analyzed retrospectively in 111 patients with acute paraquat intoxication.

RESULTS43 cases (38.7%) of all the 111 patients survived and the other 68 cases (61.3%) died. The patient, whose paraquat concentration was not more than 8.0 µg/ml in plasma and 276.0 µg/ml in urine, could survive. But some patients could die, only if there was no paraquat found in plasma. The paraquat levels in plasma and urine were significantly lower in survivors [(0.82 ± 1.70), (28.12 ± 51.17) µg/ml] than in nonsurvivors [(9.32 ± 12.04), (384.53 ± 597.93) µg/ml, respectively] (P < 0.01). The levels of leukocyte count, serum creatinine, aspartate aminotransferase (AST), and amylase were significantly higher in nonsurvivors than in survivors (P < 0.05, P < 0.01). In addition, metabolic acidosis was easier to appear in nonsurvivors. The multiple logistic regression analysis indicated that the paraquat concentration in plasma and urine, leukocyte count, creatinine and base excess were all related to survival.

CONCLUSIONThe higher paraquat concentration in plasma and urine, leucocytosis, renal dysfunction and metabolic acidosis are all important factors for the prognosis of paraquat intoxication.

Acidosis ; Adolescent ; Adult ; Aged ; Female ; Humans ; Kidney Diseases ; Leukocytosis ; Male ; Middle Aged ; Paraquat ; blood ; poisoning ; urine ; Prognosis ; Retrospective Studies ; Young Adult

BACKGROUNDHuman piebaldism is a rare autosomal dominant condition characterized by congenital white forelock and depigmented patches of skin, typically on the forehead, anterior trunk and extremities. Mutations in the KIT gene have been proposed to be responsible for the underlying changes in this disorder. The aim of this study was to identify gene mutation in a Chinese family with piebaldism.

METHODSA Chinese family with piebaldism presenting with white forelock and large depigmented skin macules on the abdomen, arms and legs was collected. DNA was isolated from peripheral blood of the family members. The encoding exons with flanking intron regions of the KIT gene were analyzed by polymerase chain reactions (PCR) and direct DNA sequencing. Besides, DNA extracted from 100 ethnically matched population individuals was as controls.

RESULTSA heterozygous missense mutation c.2590T > C was identified in the patients of the family. This mutation converted a serine residue to proline (p.Ser864Pro). The mutation was not found in their unaffected family members or normal controls.

CONCLUSIONA novel missense mutation c.2590 T > C was found and it might play a significant role in the piebaldism phenotype in the family.

Child ; Humans ; Male ; Mutation, Missense ; Piebaldism ; genetics ; Proto-Oncogene Proteins c-kit ; genetics ; physiology