Adenocarcinoma, Mucinous ; classification ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; classification ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Mucin-1 ; metabolism ; Mucin-2 ; metabolism ; Mucins ; metabolism ; WT1 Proteins ; metabolism

G,the noval insertion mutation of c.2298_2299insC is identified in Chinese patients.

To investigate the effect of Jiawei Foshou San and its various combined administration on hepatic P450 enzyme activity and hepatocyte morphology in rats. Rats were orally administered with drugs for four weeks and then sacrificed to prepare liver microsomes. The liver microsomes were incubated with the cocktail method; The metabolites were determined with the rapid liquid chromatography with tandem mass spectrometry (LC-MS/MS) to investigate the hepatocyte P450 enzyme activity. In addition, the hepatic pathological changes were observed by using the hematoxylin and eosin (HE) staining. Compared with the control group, the enzyme activity of CYP1A2 and CYP3A4 in the Jiawei Foshou san group showed a significant rise (P < 0.05); the enzyme activity of CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in the ferulic acid + ligustrazine group and the ligustrazine + tetrahydropalmatine group showed a significant rise (P < 0.05) ; the enzyme activity of CYP1A2, CYP2D6 and CYP2E1 in the ligustrazine group showed a significant rise (P < 0.05); the enzyme activity of CYP3A4 in the ferulic acid group showed a significant reduction (P < 0.05). After the administration with various drugs, the hepatocyte morphologies in the ferulic acid group and the ligustrazine group were normal. The pathological changes were observed in the tetrahydropalmatine group, such as unclear boundary of hepatic lobules, disordered hepatic cell arrangement, blurred edge, anisokaryosis and infiltration of inflammatory cells. The ferulic acid + tetrahydropalmatine group, the ligustrazine + tetrahydropalmatine group and the Jiawei Foshou San group also showed inflammatory infiltration, but with less pathological changes, particularly the Jiawei Foshou San group. The study result shows that Jiawei Foshou San can induce the enzyme activity of CYP1A2 and CYP3A4, and ligustrazine may be the effective substance for inducing CYP1A2. Its combination with ferulic acid and ligustrazine can significantly reduce the liver toxicity of tetrahydropalmatine.
Animals ; Cytochrome P-450 Enzyme System ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hepatocytes ; drug effects ; enzymology ; Microsomes, Liver ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley

Objective To compare the transplant-related toxicity and the efficacy of busulfan/fludarabine (Bu/Flu) and busulfan/cyclophosphamide (Bu/Cy) as conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia(AML) in the first complete remission (CR1).Methods Totally 32 AML-CR1 patients underwent allo-HSCT were divided into Bu/Cy (Bu 3.2 mg· kg-1 · d-1,7-4 days before transplantation; Cy 60 mg · kg-1 · d-1,3-2 days before transplantation) and Bu/Flu (Bu 3.2 mg · kg-1 · d-1,5-2 days before transplantation; Flu 30 mg · m-2·d-1,6-2 days before transplantation) groups.The regimen-related toxicity (RRT),incidence and severity of graft-versus-host disease (GVHD),3-year cumulative relapse rate,non-relapse mortality (NRM),3-year event-free survival (EFS) rate and overall survival (OS) rate were compared between the two groups.Results The median follow-up duration was 617.5 (6-1261) days.All patients achieved successful engraftment on 30 day after transplantation.There were no significant differences in the median time to neutrophil engraftment (P =0.121) and platelet engraftment (P =0.171) between the two groups.The median duration of neutrophil count under 0.1 × 109/L and platelet count under 20 × 109/L in the Bu/Cy group were significantly longer than those in the Bu/Flu group (P =0.000 and P =0.047).The incidence of grades Ⅱ-Ⅳ RRT were 68.8％ and 25.0％ (P =0.032) in the Bu/Cy and the Bu/Flu groups,respectively.There were no significant differences in the incidence of acute GVHD (P =0.149),chronic GVHD (P =0.149),incidence of NRM (P =0.333),3-year cumulative relapse rates (P =0.834),3-year EFS rate (P =0.362) and OS rate (P =0.111) between the two groups.Conclusion Compared with Bu/Cy,Bu/Flu is a myeloablative condition regimen with milder bone marrow suppression and lower RRT incidence rate in allogeneic HSCT for AML-CR1 patients without compromising the efficacy.

Humans ; Hypertensive Encephalopathy ; etiology ; Purpura, Schoenlein-Henoch ; complications ; diagnosis

In the present experiments, the characteristics of the electrical responses to stimulation of the cerebellum in crucian carp Mauthner cell were explored with microeletrode intracellular recording technique. A composite excitatory postsynaptic potential (cerebellum-evoked EPSP) could be induced from the soma, the ventral dendrite and the proximal end of the lateral dendrite in crucian carp Mauthner cell (M-cell) on either side by stimulation of the ventrolateral region of the cerebellum. The cerebellum-evoked EPSP presented characteristics of relatively short latency (0.63+/-0.09 ms), longer duration (5.49+/-1.13 ms), graded amplitude and dependence on stimulation frequency. Stimulation of the cerebellum with higher intensity always activated the M-cell orthodromically. Multiple intracellular recordings showed that the cerebellum-evoked EPSP originated in the distal end of the ventral dendrite. The results suggest that the cerebellum-M-cell pathway is probably composed of a group of neuron chains with different numbers of synaptic relays projecting to the distal end of the ventral dendrite in order of length of the chains.
Animals ; Carps ; physiology ; Cerebellum ; physiology ; Dendrites ; physiology ; Electric Stimulation ; Excitatory Postsynaptic Potentials ; physiology ; Neurons ; physiology ; Synapses ; physiology ; Synaptic Transmission ; physiology

AIMTo study the effect of recombinant hirudin (rH) on tPA-induced fibrinolysis and the possible mechanism of its action.

METHODSThe effect of rH on thrombin-fibrin complex (Th-Fn) was detected by 99mTc labeled rH. In the in vitro clot lysis, tPA as plasminogen activator, and recalcified plasma as plasminogen resource were used to study the influence of rH on fibrinolysis by detecting TAFIa, D-Dimer and FXIII.

RESULTSIn a canine model of femoral artery thrombosis, a clear radioactivity strip was imaged in 30 - 60 min on a part image, and the femoral vein thrombosis developed at 30 min. rH efficiently inhibited clot regeneration. Addition of TM could inhibit clot lysis obviously, and CPI could shorten the delay of clot lysis which due to TAFIa. There was a dose-dependent relationship with TM concentration and TAFI activation. FXIII activation was inhibited by low concentration of rH ( < or = 0.2 u x mL(-1)), and the level of fibrinolysis product, D-Dimer, increased.

CONCLUSIONrH could inhibit the thrombin binding to fibrin. rH inhibited the activation of TAFI and FXIII by combining with thrombin which resulted in enhancement of thrombolysis.

Animals ; Blood Coagulation ; drug effects ; Carboxypeptidase B2 ; metabolism ; Carboxypeptidases ; antagonists & inhibitors ; Dogs ; Factor XIII ; metabolism ; Femoral Artery ; Femoral Vein ; Fibrinolysis ; drug effects ; Fibrinolytic Agents ; pharmacology ; Hirudins ; genetics ; pharmacology ; Male ; Plant Proteins ; pharmacology ; Protease Inhibitors ; Recombinant Proteins ; pharmacology ; Thrombomodulin ; metabolism ; Thrombosis ; metabolism ; Venous Thrombosis ; metabolism

Objective To observe the expression levels of matrix metalloproteinase-2 and 9 (MMP-2, MMP-9) in wound tissue and wound effusion in patients with chronic pressure ulcers treated with an alternating pres- sure relief mattress,and to correlate these observations with wound healing.Methods A total of 24 patients with chronic pressure ulcers were recruited and divided into two groups :one treated with an alternating pressure relief mat- tress and the other without,in addition to conventional treatment for pressure ulcers.The expression of MMP-2 and MMP-9 in the wound tissue and its exudate were amplified with a reverse transeriptase-polymerase chain reaction (RT-PCR) and analyzed using quantitative gelatin zymography.Wound healing was also observed and assessed using the pressure ulcer scale for healing (PUSH).Results The wounds were observed to heal well in both groups,as indicated by a significant decrease in the PUSH scores.Statistical analysis revealed a significant difference between the two groups with regard to the PUSH score on the 21st day after initiation of the study.With the healing of the pressure ulcers,the expression both MMP-2 and MMP-9 decreased.On the seventh and the 21st days,the expression of MMP-2 and MMP-9 in patients treated with an alternating pressure relief mattress was significantly less than in those without the mattress.Conclusion MMP-2 and MMP-9 can be biomarkers for the healing of pressure ulcers. An alternating pressure relief mattress is helpful for treating pressure ulcers.

The release behavior of single pellet was investigated by LC/MS/MS method with tamsulosin hydrochloride (TSH) as the model drug of the research and then the pellets were divided into four groups according to the drug loading. Comparison of dissolution profiles of each group and capsule were performed using f1 and f2 factor methods to study the difference and similarity. The release profiles of single pellet, each group and capsule were analyzed using principle component analysis (PCA). The particle system was built through Matlab to get the target release profile. The result of this research demonstrated the release behavior of single pellet correlated well with the drug loading. While the dissolution profile of capsule as a reference, the similarity factor of dissolution profiles of the lower drug loading groups were 62.2, 67.1, 53.9, respectively and, 43.3 for highest drug loading group. The particle systems with different pellet distribution and same release profiles were built through release behavior of single pellet. It is of significance to investigate the release behavior of single pellets for studying the release regularity of multiple-unit drug delivery system.
Capsules ; Chemistry, Pharmaceutical ; Chromatography, Liquid ; Delayed-Action Preparations ; Drug Delivery Systems ; Drug Liberation ; Principal Component Analysis ; Sulfonamides ; administration & dosage ; chemistry ; Tandem Mass Spectrometry ; Technology, Pharmaceutical

To study the pharmacokinetic process of Danshensu in cerebal ischemia injury model rats and the correlation with its anti-cerebral ischemia effect. In this study, the middle cerebral artery occlusion (MCAO) model was established, in which all of the rats were intravenously injected of Danshensu at a single dose of 40 mg x kg(-1). The HPLC-DAD method was applied to determine the plasma concentration of Danshensu at different time points and draw the drug-time curve. Meanwhile, the superoxide dismutase (SOD) and the lactate dehydrogenase (LDH) activity were determined to draw the time-effect curve. The DAS 3.2. 6 software was used to process the data, analyze their correlation, compare the pharmacokinetic difference between model and normal rats after the administration of the same doses of Danshensu and the changes in pharmacodynamic indicators of model rats after the administration, and evaluate the effect of Danshensu in treating the cerebral ischemia disease. According to the results, the pharmacokinetic processes of Danshensu in the cerebral ischemia-reperfusion and normal rats were consistent to the two-compartment model. The main pharmacokinetic parameters were: t1/2alpha were (0.267 +/- 0.026), (0.148 +/- 0.020) h;t1/2beta were (1.226 +/- 0.032), (1.182 +/- 0.082) h; AUC0-infinity were (42.168 +/- 4.007), (26.881 +/- 1.625) mg x L(-1) x h. After the cerebral ischemia-reperfusion, the activity of SOD decreased and the activity of LDH increased. Danshensu could inhibit the decrease in the SOD activity and the increase in the LDH activity within a certain period of time. This indicated that Danshensu could stay longer in cerebral ischemia-reperfusion rats than in normal rats and eliminated more slowly, which reflected the rationality of Danshensu in the clinical treatment of cerebral ischemia diseases. Danshensu's effect against the cerebral ischemic injury may be related with its level in vivo. Its plasma concentration is positively related to the SOD activity and negatively related to the LDH activity.
Animals ; Brain Ischemia ; drug therapy ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry