Objective To investigate whether delayed treatment with exogenous kallikrein on neurogenesis after focal cortical infarction in stroke-prone renovascular hypertensive rats (RHRSP). Methods Seventy-two RHRSP were divided into 3 groups. Twenty-four rats were given human tissue kallikrein ( 1.6 × 10-2 PNAU/kg) and 24 rats were given vehicle through tail venous daily for 2 or 6 days consecutively starting at the 24th hour after distal middle cerebral artery occlusion (MCAO). 24 rats underwent sham-operation. Cell proliferation was examined by using 5'-bromo-2'-deoxyuridine (BrdU, 50 mg/kg). Rats were respectively sacrificed 3, 7, 14 or 28 days after MCAO. Results Treatment with kallikrein significantly increased the number of BrdU+ cells in the ipsilateral subventricular zone (SVZ) (304.0±73. 9 vs 167.0±32.2 vs 56.0±12.2 at 7 d after operation, q =7.165, 12.916 and 5.751 respectively,all P<0.05) and in the peri-infarction region (490.0±82.0 vs 308.0±51.5 vs 49.0± 9.5 at 7 d after operation, q = 7.920, 19.184 and 11.264 respectively, all P < 0.01 ), and increased the number of BrdU+/DCX+ cells (225.0±13.6 vs 98.0±9.6 vs 23.0±5.6 at 7 d after operation, q = 30.731,48.735 and 18.004 respectively,all P < 0.01) in the ipsilateral SVZ compared with the vehicle group or the sham-operated group, which began on the 3 day, peaked in 7--14 days after MCAO, and then gradually decreased. Compared with the vehicle group, exogenous kallikrein markedly increased the number of BrdU+/NeuN+ cells (21.0±3.4 vs 13.0±2.6 at 14 d, P =0.001 ) in the peri-infarction region after MCAO. The kallikrein group showed a better functional improvement than the vehicle group after stroke ( all P < 0.05). Conclusion Our study suggests that administration of exogenous kallikrein at 24 h after cortical infarction enhances the SVZ neuroblasts proliferation, migration, and selective differentiation and improves functional recovery after stroke.

BACKGROUND:In the process of designing knee joint prosthesis and operating total knee arthroplasty for the Chinese people, we should not only take into account the proximal tibial anatomical characteristics and the difference of geometry, but also should pay attention to the differences between different races. OBJECTIVE:To compare the anatomical morphological differences between Mongolian and Han nationality through measuring the CT tomography scanning and three-dimensional reconstruction measurement of tibia proximal part of Han and Mongolian nationality, so as to provide the data references for prosthesis selection used for total knee arthroplasty. METHODS:Total y 60 patients who received the treatment at the Department of Joint Surgery were col ected, and divided into Han nationality and Mongolian nationality groups (n=30/group, 15 males and 15 females in each group). The age was (36.00+7.22) years old. 16-row helical CT scan (American GE Lightspeed 16) was used for spiral scanning, slice thickness 0.625 mm. Scanning images were exported in DICOM format and saved. Digital three-dimensional reconstruction measurement was conducted using Mimics 15.0 three-dimensional reconstruction software. The tibial plateau width, anteroposterior diameter of the medial tibial plateau and lateral anteroposterior diameter were measured respectively to observe whether there were any differences among sex, sides and nationality. RESULTS AND CONCLUSION:There were no significant differences in the above indicators between left and right sides (P>0.05). There were significant differences in tibial plateau width, anteroposterior diameter of the medial tibial plateau and lateral anteroposterior diameter between males and females, and Han and Mongolian nationality groups (P<0.05). Specific performed in:(1) There was significant difference in the morphological measurement parameters of proximal tibia between sex for Han and Mongolian nationality, and the mean value of male was larger compared with that of female. (2) There was certain significant difference in the part of the parameter indicators between Han and Mongolian nationality groups. These results suggest that the prosthesis should be chose and placed correctly according to the differences of morphological characteristics, gender, nationality, region of the Chinese people. (3) Digital three-dimensional reconstruction technology and individualized design can choose suitable prosthesis for different people, so as to ensure a good repair effect in patients after total knee replacement.

The microbial counts, type, as well as relationship between microbial counts and the temperature of water in reticulating water system of heating pipeline in Taiyuan were studied, which the main biofouling harmful microbes included slimeforming heterotrophic bacteria, sulfate reducing bacteria, iron bacteria and fungi, respectively. The results showed that the harmful microbes in water system were lower than that of control guideline during heating period, whereas the microbes were higher than that of control guideline, which would result in biofouling of water tube during non- heating period.

Aged ; Aged, 80 and over ; Biomarkers, Tumor ; urine ; Carcinoma, Transitional Cell ; urine ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; Male ; Microtubule-Associated Proteins ; genetics ; Middle Aged ; Neoplasm Proteins ; genetics ; RNA, Messenger ; urine ; Reverse Transcriptase Polymerase Chain Reaction ; Urinary Bladder Neoplasms ; urine

OBJECTIVETo explore the relationship of beta-catenin and sensitivity to Bortezomib of myeloma cell lines.

METHODSMyeloma cell lines RPMI8226, CZ-1 and NCI-H929 were treated with Bortezomib and 2ME2, alone or in combination. Typan blue dye exclusion and modified MTT were used to assess the cell viability with or without treatment. Annexin V-FITC and PI staining was performed to detect apoptosis rate. RT-PCR was used to detect beta-catenin mRNA and western blot to analyze beta-catenin protein.

RESULTSThe basic expression level of beta-catenin was different in tested myeloma cell lines: RPMI8226 was the most while NCI-H929 the least and CZ-1 the intermediate. IC50 of RPMI8226, CZ-1 and NCI-H929 were (49.8 +/- 0.6), (24.7 +/- 0.4) and (8.4 +/- 0.2) nmol/L, respectively. After the treatment of Bortezomib (at 0, 1, 5, 10 nmol/L), beta-catenin level of tested cell lines accumulated in a time and dose dependent manner for western blot, while no significant change was observed in the result of RT-PCR. The beta-catenin protein levels in the Bortezomib (5 nmol/L) and 2ME2 (1 micromol/L) treated cell group were much lower than that in Bortezomib (5 nmol/L) group, the decrease of the gray scale of beta-catenin/beta-actin was 64.03% for RPMI8226, 52.56% for CZ-1, 51.48% for NCI-H929, and the apoptosis rates were 8.00, 1.86 and 1.19 times increase compared to untreated group.

CONCLUSIONMyeloma cell lines with higher beta-catenin level are less sensitive to Bortezomib, and combination treatment of low dose 2ME2 and Bortezomib can reduce beta-catenin accumulation and enhance the sensitivity to Bortezomib.

Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Multiple Myeloma ; metabolism ; pathology ; Pyrazines ; pharmacology ; RNA, Messenger ; genetics ; beta Catenin ; genetics ; metabolism

The aim of this study was to investigate the effect of arsenic trioxide (As(2)O(3)) combined with bortezomib on the proliferation, apoptosis and beta-catenin level in myeloma cell lines. Myeloma cell lines RPMI8226, CZ-1 and NCI-H929 were treated with As(2)O(3) and bortezomib alone or in combination for 48 hours. Trypan blue dye exclusion and modified MTT were used to assess the cell viability. Flow cytometry with Annexin V-FITC and PI staining was used to detect the apoptosis rate. The beta-catenin level was analyzed by Western blot. The results showed that IC(50) of bortezomib to RPMI8226, CZ-1 and NCI-H929 were 46.9, 20.7 and 6.8 nmol/L, respectively. After the combination treatment with bortezomib (5 nmol/L) and As(2)O(3) (1 micromol/L), the cell viability of RPMI8226, CZ-1 and NCI-H929 decreased from 88.99%, 72.23%, 51.06% to 54.01%, 39.59%, 25.00%(p<0.05), the apoptosis rate increased from 11.1+/-0.1%, 26.8+/-1.7%, 46.8+/-5.5% to 36.1+/-2.2%, 60.4+/-3.8%, 76+/-5.6% (p<0.01) respectively. The Q value of two groups lies between enhancement and significant enhancement (1.198 - 3.75). Besides, beta-catenin levels in tested cell lines were decreased to 24.15%, 31.85%, 33.72% of their basic constitutions respectively (p<0.05). It is concluded that combination treatment of As(2)O(3) and bortezomib can enhance the proliferation inhibition and apoptosis induction of bortezomib to myeloma cell lines, reduce beta-catenin level, and increase the sensitivity of myeloma cell lines to bortezomib.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Proliferation ; drug effects ; Drug Synergism ; Humans ; Multiple Myeloma ; metabolism ; pathology ; Oxides ; pharmacology ; Pyrazines ; pharmacology ; Tumor Cells, Cultured ; beta Catenin ; metabolism

OBJECTIVETo explore the molecular mechanisms involved in the patient with congenital FV deficiency.

METHODSActivity of FV was determined by biochemical method. The PCR products of FV gene was analysed by directly sequencing or sequencing after cloned into T-vector. The mutative FV gene was analysed by restriction enzyme analysis in the proband and her family members.

RESULTSA homozygous missense mutation G5729T resulting in Gly1880Val was revealed in the proband and confirmed in the family screening. Structure-function studies of the factor V mutants (Gly1880Val) demonstrated the importance of Gly1880 for structural stability of the Factor V.

CONCLUSIONG5729T mutation of FV gene is related to the pathogenesis of congenital FV deficiency.

Adult ; DNA Mutational Analysis ; Factor V ; genetics ; metabolism ; Factor V Deficiency ; blood ; congenital ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Polymerase Chain Reaction

BACKGROUNDMarked interindividual variation exists in blood pressure response to benazepril, which is considered to have genetic basis. Our objectives were to evaluate whether the E112D polymorphism in the prolylcarboxypeptidase (PRCP) gene has impact on blood pressure response to benazepril.

METHODSHypertensive patients from Huoqiu County and Yuexi County of Anhui Province received daily treatment with an oral dosage of 10 mg benazepril for 15 days. Genotypes of the E112D polymorphism in the PRCP gene were determined by TaqMan SNP genotyping assay. Multivariate linear and Logistic regressions using generalized estimating equation model were performed in a total of 1092 patients to evaluate the association of PRCP genotypes and blood pressure response to benazepril.

RESULTSPatients carrying ED or DD genotype had a less systolic blood pressure reduction (adjusted beta = -3.7 + or - 1.1, P < 0.001), a less diastolic blood pressure reduction (adjusted beta = -3.1 + or - 0.8, P < 0.001) and a lower percentage of reaching target blood pressure defined as SBP lower than 140 mmHg and DBP lower than 90 mmHg (adjusted OR = 0.6, P = 0.005) than those patients carrying EE genotype. In addition, the results from stratified analysis by county (Huoqiu or Yuexi) were similar to those observed in the pooled population.

CONCLUSIONSOur data suggest that the E112D polymorphism in the PRCP gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril treatment in hypertensive patients of Anhui Province, China.

Adult ; Aged ; Antihypertensive Agents ; therapeutic use ; Benzazepines ; therapeutic use ; Blood Pressure ; drug effects ; Carboxypeptidases ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; genetics ; physiology ; Young Adult

OBJECTIVETo investigate the effect of nifedipine on the non-selective inward current of cochlear Hensen cell induced by ATP in high concentrations.

METHODSThe organ of Corti was treated using enzyme, and then dissociated mechanically to isolate Hensen cells. The whole cell patch-clamp technique was used to record ion currents in Hensen cells which had integrated border, round shape and translucent intracellular cytoplasm. Drugs were delivered to the cell by a micro-manifold consisting made by three 100 microm diameter microtubules, including 0.1 mmol/L ATP, 1 mmol/L ATP, 10 mmol/L ATP, 0.1 mmol/L ATP + 0. 1 mmol/L suramin (purinergic antagonist), stimulation of extracellular fluid alone, 140 mmol/L CsCl (replace KCL in intracellular fluid) + 1 mmol/L ATP, 40 mmol/L TEA (blocker of potassium channel) + 1 mmol/L ATP, and 1 mmol/L ATP + 10 micromol/L nifedipine, respectively.

RESULTSWhen isolated Hensen cell was given 0.1 mmol/L (n = 10), 1 mmol/L (n = 10), 10 mmol/L( n = 6) ATP separately, an inward ion current could be recorded, which enhanced with increased ATP concentration and showed dose-dependence. Further study indicated that the inward ion current could be inhibited by 0.1 mmol/L suramin (n = 5), 140 mmol/L CsCl (n = 5) and 40 mmol/L TEA (n = 5). There was no ion current be recorded when the cell was stimulated with the extracellular fluid alone, neither inward nor outward. However, the inward ion current vanished and an outward ion current appeared instead, when 1 mmol/L ATP and 10 micromol/L nifedipine were given together (n = 5).

CONCLUSIONSAn inward current was evoked in isolated Hensen cell by ATP in high concentrations. This inward current seems to be associated closely with potassium channels without the participation of mechanical channels. Nifedipine can inhibit this inward current and induce an outward current, which is similar to the normal potassium current in isolated Hensen cell. It suggests that nifedipine have partly protective effect on the function of cochlea by inducing modulate of the potassium circle of cochlea in Hensen cell's tache.

Adenosine Triphosphate ; pharmacology ; Animals ; Cochlea ; cytology ; Female ; Guinea Pigs ; Labyrinth Supporting Cells ; drug effects ; metabolism ; Male ; Nifedipine ; pharmacology ; Patch-Clamp Techniques ; Potassium Channels, Inwardly Rectifying ; drug effects

OBJECTIVETo explore the clinical significance of serum free light chain (sFLC) levels in nonsecretory multiple myeloma (NSMM).

METHODSNine NSMM patients were hospitalized in our department from Feb 2002 to Sep 2006 and no M-components was found in their serum and urine by immunofixation electrophoresis (IFE). sFLC was assayed by immuno-nephelometry. The clonality of sFLC was estimated by serum kappa:lambda sFLC ratio. Meanwhile, serum immunoglobulin, total kappa and lambda light chain level were also determined in these patients.

RESULTSIncreased serum concentrations of either kappa or lambda sFLC (and abnormal kappa/lambda ratios) were detected in 6 of 9 patients with NSMM although their serum immunoglobulin levels were not elevated and total kappa:lambda light chain ratios (1.32 - 2.20) were in the reference range. All the 9 patients had clonal IgH gene rearrangements.

CONCLUSIONQuantification of sFLC by immuno-nephelometry is more sensitive than that of serum total light chain measurement and is helpful in estimating the clonality of the light chain in patients with NSMM.

Adult ; Female ; Humans ; Immunoglobulin Light Chains ; blood ; Male ; Middle Aged ; Multiple Myeloma ; blood ; Nephelometry and Turbidimetry ; Sensitivity and Specificity