OBJECTIVETo explore the myelo-protection effect of mdr1 transfected cord blood cells (CBMNCs) graft against high-dose homoharringtonine leukemia-bearing severe combined immunodeficient (SCID) mice model.

METHODSMultidrug resistant (mdr1)gene was transferred into CBMNCs by a retrovirus vector, containing full-length cDNA of human mdr1 gene. CBMNCs and high-titer retrovirus supernatant were cocultured with cytokine combinations for 5 - 6 days. The SCID mouse models bearing human HL-60 cell leukemia were divided into three groups. Group A received tail vein injection of 2 x 10(6) mdr1 gene transduced CBMNCs at day 1 and 3, groups B and C 2 x 10(6) un-transduced CBMNCs and same volume of normal saline, respectively. The 3 groups of the mouse model were treated with weekly escalated doses of homoharringtonine. The peripheral white blood cell (WBC) counts, the human leukemia cells percentage in peripheral blood, the histological findings of main organs were assayed. The CD33 positive HL-60 cells in bone marrow were determined by flow cytometry. The function and expression of mdr1 gene were examined by PCR, immunochemistry (IC) and DNR extrusion test in vivo.

RESULTS(1) mdr1 gene was transferred into CBMNCs successfully and the transfection frequency was 30%. (2) Leukemia SCID mice were xenotransplanted with mdr1-transfected BMMNCs by a programmed procedure and could be used as a valuable model for in vivo evaluating myelo-protection effects. (3) The transfected mice could tolerate homoharringtonine 5 approximately 6 folds higher than conventional dose and kept peripheral WBC count at a mean of 3 x 10(9)/L, with the peripheral human myeloid leukemia cells percentage decreasing to less than 5%. Histological examination showed that there was no leukemia infiltration in the main organs, the CD33 positive HL-60 cells in bone marrow were less than 5%. (4) The repopulation frequency of the transfected CBMNs in marrow were 9.13%. DNR extrusion test confirmed that the P-gp product maintained its biological function in the marrow.

CONCLUSIONmdr1 transferred-human CBMNC can xenotransplanted and repopulated in leukemia-bearing SCID mouse and are protected from chemotherapy-induced myelosuppression.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; therapeutic use ; Cord Blood Stem Cell Transplantation ; methods ; Female ; Fetal Blood ; cytology ; Genetic Vectors ; HL-60 Cells ; Harringtonines ; administration & dosage ; adverse effects ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; pathology ; surgery ; Leukocytes, Mononuclear ; cytology ; metabolism ; transplantation ; Male ; Mice ; Mice, SCID ; Random Allocation ; Retroviridae ; genetics ; Transfection ; Treatment Outcome ; Xenograft Model Antitumor Assays

OBJECTIVETo prepare cryptotanshinone (CT)-cyclodextrin inclusion compound and improve dissolution of CT.

METHODInclusion ratio was determined by plotting the phase solubility curve of CT versus hydroxypropyl-beta-cyclodextrin (HPCD). CT-cyclodextrin inclusion compound was made by wet grinding method. Properties of the inclusion compound was investigated by in vitro dissolution test, DTA and IR spectrum.

RESULTInclusion ratio of CT versus HPCD was 1:1. Dissolution of CT-HPCD inclusion compound at 45 min was 21.6 times of material drug.

CONCLUSIONDissolution of CT was improved remarkably in CT-HPCD inclusion compound. The complexation force of the inclusion compound was hydrogen bond formed by carbonyl group of CT and hydroxyl group of HPCD.

2-Hydroxypropyl-beta-cyclodextrin ; Biological Availability ; Drug Carriers ; Drugs, Chinese Herbal ; chemistry ; Phenanthrenes ; chemistry ; isolation & purification ; Salvia miltiorrhiza ; chemistry ; Solubility ; Technology, Pharmaceutical ; methods ; Time Factors ; beta-Cyclodextrins ; chemistry

OBJECTIVETo investigate the effects of glucocorticoid receptor antagonist-M8046 on the behavior and the cyclooxygenase-2/prostaglandin E2( COX-2/PGE2) expression in spinal cord dorsal horn and dorsal root ganglia (DRG) in chronic constrictive injury (CCI) rats.

METHODSOne hundred and forty-four male SD rats were randomly divided into 4 groups, 36 rats in each group: Sham operation group (Sham), chronic constrictive group (CCI), M8046 treated group (M8046) and solvent controlled group (Sc). M8046 3 mg/(kg x d) intraperitoneal injection was given after operation in group M8046. Paw thennal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured on 2 pre-operative and 1, 3, 7, 10, 14 post-operative days. The spinal cord and L15 DRG of the operated side was removed at 3, 7, 14 days after surgery. The change of COX-2 and PGE2 expression was determined by immunohistochemical staining and ELISA separately.

RESULTSPTWL and PMWT in CCI group were significantly lower than those in Sham group on every post-operative day (P < 0.05). PTWL and PMWT in M8046 group were significantly higher than those in CCI group on 7, 10, 14 post-operative day (P < 0.05). In spinal dorsal horn, the level of COX-2 and PGE2 expression in CCI group was significantly higher than that in Sham group (P < 0.05). M8046 could significantly attenuate the activation of COX-2 and PGE2 induced by CCI (P < 0.05). The expression of COX-2 and PGE2 in DRG was similar to that in spinal dorsal horn.

CONCLUSIONThe effects of M8046 ameliorate the CCI-induced neuropathic pain may be related to attenuate the expression of COX-2 and PGE2 in spinal cord and DRG.

Animals ; Cyclooxygenase 2 ; metabolism ; Dinoprostone ; metabolism ; Ganglia, Spinal ; drug effects ; metabolism ; Male ; Neuralgia ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; antagonists & inhibitors ; Spinal Cord ; drug effects ; metabolism

OBJECTIVETo evaluate the efficacy of acupuncture analgesia in reducing patient's discomfort during colonoscopy.

METHODSEighty outpatients scheduled to undergo colonoscopy were randomly divided into an electroacupuncture (EA) group and a control group, 40 cases in each group. The patients in the EA group received electroacupuncture analgesia at the right Zusanli (ST 36) and Shangjuxu (ST 37), and left Yinlingquan (SP 9) and Sanyinjiao (SP 6), and bilateral Hegu (LI 4) from 30 minutes before colonoscopy to the end of colonoscopy. And the control group did not receive any treatment. Blood pressure (BP), heart rate (HR) in the both groups were continuously monitored during colonoscopy; the pain degrees during colonoscope inserting and passing the sigmoid, splenic flexure and hepatic flexure were observed. The time to reach cecum, adverse reaction and patient's satisfactoriness were recorded.

RESULTSColonoscopy was well tolerated in all the 80 patients. Pain degrees during colonoscope inserting and passing the sigmoid and splenic flexure in the EA group were significantly lower than those in the control group (P < 0.01); the time to reach cecum in the EA group (9.58 +/- 3.386) min was significantly shorter than that in the control group (12.96 +/- 6.4) min (P < 0.05); patient's satisfactoriness in the EA group was significantly higher than that in the control group (P < 0.05). There was no significant difference in HR and BP values between the two groups.

CONCLUSIONAcupuncture analgesia can effectively alleviate the discomfort of patients during colonoscopic examination, shorten the duration of colonoscopy, with a higher satisfactoriness of the patient.

Acupuncture Analgesia ; methods ; Acupuncture Points ; Adult ; Colonoscopy ; methods ; Female ; Humans ; Male ; Middle Aged

This study was aimed to investigate the expression of FLT3 internal tandem duplication (FLT3-ITD) in pediatric patients with acute myeloid leukemia (AML) and to analyse the clinical features of patients with mutations and the relation of FLT3-ITD with multidrug resistance gene 1 (mdr1). RT-PCR was used to determine the expressions of FIT3-ITD and mdr1 gene in bone marrow samples from 81 new diagnosed pediatric patients with AML, the cytogenetics and immunophenotypes of bone marrow cells were routinely examined. The results indicated that the FLT3-ITDs were detected in 8 out of 81 pediatric patients (9.88%) and all mutations detected were hybrid, while less frequently this mutation was detected in adult patients. Although they were irrelevant with sex and immunophenotypes, the mutations seemed predominant in older pediatric patients. The leukocyte counts and bone marrow blast cell counts in pediatric patients with FLT3-ITD at diagnosis were higher than those in pediatric patients without FLT3-ITD (p = 0.001 and p = 0.041 respectively), but the normal chromosomes were found in most pediatric patients with FLT-ITD. The patients with FLT3-ITD had lower induction remission rate (only 25%), but the patients without FLT3-ITD had higher remission rate (76.1%). According results detected by RT-PCR, the mdr1 gene was found in 27 pediatric patients, but only 3 out of 8 pediatric patients with FLT3-ITD were detected to express both FLT3-ITD and mdr1, which suggests unrelation between FLT3-ITD occurrence and mdr1 expression. It is concluded that the FLT3-ITD is frequent mutation in pediatric patients with AML, the prognosis is worse and the induction remission rate is lower in these patients, but the FLT3-ITD not relates with the mdr1, which suggests that the common MDR modulators may be un effective for therapy of the patients with FLT3-ITD.
ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Adolescent ; Child ; Child, Preschool ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Female ; Gene Duplication ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Male ; Mutation ; Prognosis ; Tandem Repeat Sequences ; fms-Like Tyrosine Kinase 3 ; genetics

OBJECTIVETo evaluate the long-term efficacy and safety of endoscopic tissue adhesive(N-octyl-α-cyanoacrylate) injection for the treatment of gastric varices.

METHODSA retrospective study was performed to review the clinical and follow up data of 169 patients with gastric variceal who received tissue adhesive injection at the Fudan University Affiliated Zhongshan Hospital between April 2004 and December 2011.

RESULTSThere were 128 males and 41 females with a mean age of 56.8(37-85) years old. One hundred and thirty-one patients received one injection, 38 received two injections or more with a mean of 1.12 per patient. Volume of injection ranged from 1 to 3 ml(mean, 1.7 ml). Eighty-three patients received adhesive injection alone, 231 received injection combined with ligation, 50 received combined sclerotic agent injection. All the patients had follow up ranging from 1 to 78 months(mean, 3.4 months). The treatment outcome was satisfactory in 130 patients(76.9%), good in 36(21.3%), and ineffective in 3(1.8%). The rate of ectopic embolization was 3.0%, and the rate of early re-bleeding was 1.2%. Postoperatively there were no septic complications or esophageal stricture. There were no deaths within 2 weeks.

CONCLUSIONInjection of tissue adhesive under endoscopic guidance for treatment of gastric varices is convenient, safe and effective.

Adult ; Aged ; Aged, 80 and over ; Esophageal and Gastric Varices ; therapy ; Female ; Follow-Up Studies ; Gastroscopy ; Humans ; Injections, Intralesional ; Male ; Middle Aged ; Retrospective Studies ; Tissue Adhesives ; administration & dosage ; therapeutic use ; Treatment Outcome

BACKGROUNDEmergence agitation is a common problem in pediatric anesthesia, especially after sevoflurane induction and maintenance anesthesia. The purpose of this study was to investigate the effect of sufentanil to reduce emergence agitation after sevoflurane anesthesia in children undergoing adenotonsillectomy compared with fentanyl.

METHODSOne hundred and five children, aged 3 - 11 years, were randomly allocated to receive normal saline (control group), sufentanil 0.2 µg/kg (S2) or fentanyl 2 µg/kg (F2) 1 minute after loss of the eyelash reflex. Anesthesia was induced and maintained with sevoflurane. Time to tracheal extubation, recovery time, Paediatric Anesthesia Emergence Delirium (PAED) scale, and emergence behavior were assessed.

RESULTSThe incidence of severe agitation was significantly lower in S2 and F2 groups vs. the control group, 4/32 and 15/34 vs. 24/34 respectively, (P = 0.002, 0.009, respectively). PAED scales were significantly different among three groups (P = 0.007), and lower in the S2 and F2 groups than in the control group (P = 0.007 and P = 0.025, respectively). And the incidence of severe agitation and the PAED scale score was significantly different between the S2 and F2 groups (P = 0.007, P = 0.019, respectively). Time to tracheal extubation and recovery time were similar in all three groups.

CONCLUSIONSAdministration of sufentanil at 0.2 µg/kg after induction of anesthesia reduced emergence agitation in children receiving sevoflurane anesthesia for adenotonsillectomy compared with fentanyl. This was without delaying the recovery time or causing significant hypotension.

Adenoidectomy ; methods ; Anesthesia ; methods ; Child ; Child, Preschool ; Female ; Fentanyl ; therapeutic use ; Humans ; Male ; Methyl Ethers ; adverse effects ; therapeutic use ; Prospective Studies ; Psychomotor Agitation ; drug therapy ; etiology ; Sufentanil ; therapeutic use

OBJECTIVETo investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia.

METHODSTwenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy.

RESULTSCompared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43.

CONCLUSIONSLPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; chemically induced ; metabolism ; physiopathology ; Connexin 43 ; metabolism ; Lysophospholipids ; adverse effects ; Oligopeptides ; pharmacology ; Rabbits

BACKGROUNDFew reports have evaluated the efficacy of re-operation for relapse after initial surgery for hepatocellular carcinoma (HCC) with bile duct thrombosis (BDT). The aim of this study was to investigate the efficacy of initial surgery and subsequent re-operation for HCC with BDT, and their effects on prognosis.

METHODSThe clinical data of 880 patients with HCC, including 28 patients with BDT, who underwent radical hepatectomy between 1998 and 2008 in our hospital, were reviewed. The effects of BDT and re-operation on prognosis were retrospectively analyzed.

RESULTSThe 1-, 3- and 5-year survival rates were 89.3%, 46.4% and 21.4%, respectively, in 28 patients with BDT versus 91.4%, 52.9% and 20.9% in 852 patients without BDT (P>0.05). Six patients with BDT underwent re-operation after disease relapse, and their survival time was significantly longer than those who did not undergo re-operation (P<0.05). Multivariate analysis indicated that portal vein invasion and tumor size were independently associated with tumor relapse and prognosis (P<0.05). Univariate analysis and multivariate analyses showed that obstructive jaundice was not significantly correlated with tumor relapse or prognosis (P>0.05).

CONCLUSIONSHepatectomy plus BDT removal is an effective treatment option for HCC with BDT. Obstructive jaundice is not a contraindication for surgery. Re-operation after relapse can provide good outcomes if the cases are appropriately selected.

Adult ; Bile Ducts ; pathology ; Carcinoma, Hepatocellular ; diagnostic imaging ; surgery ; Female ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnostic imaging ; surgery ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Radiography ; Thrombosis ; surgery ; Treatment Outcome ; Ultrasonography

OBJECTIVETo study the Kv1.3 channel expression changes after CD4(+) and subsets CD28(null)/CD28(+)T cells activation in peripheral blood of patients with acute coronary syndrome (ACS).

METHODSCD4(+)T cell in 27 ACS patients and CD4(+)CD28(null)/CD4(+)CD28(+)T cells in 12 out of these 27 ACS patients were isolated from peripheral blood with magnetic cell sorting. The whole-cell Kv1.3 currents for three T cells were recorded with patch-clamp technique before and 72 hours after activation by purified anti-human CD3 Interferon gamma, tumor necrosis factor alpha (TNF-alpha), granzyme B mRNA expression were determined by reverse transcription-PCR before and 72 hours after activation by purified anti-human CD3 in the presence or absence of recombinant Margatoxin (rMgTX, 0.1, 1, 10 nmol/L), a specific Kv1.3 channel blocker.

RESULTSPeak Kv1.3 channel currents of CD4(+), CD4(+)CD28(null), CD4(+)CD28(+)T cells were significantly increased and the mean Kv1.3 channel numbers per cell of these cells were increased by about 90%, 60%, 80% (402 +/- 88 vs. 752 +/- 275, 553 +/- 328 vs. 874 +/- 400, 392 +/- 133 vs. 716 +/- 251, all P < 0.05) after activation compared to baseline values. Baseline CD4(+)CD28(null)T cell numbers were about 40% more than those of CD4(+)CD28(+)T cell (P < 0.05) and were similar after activation (P = 0.102). The mRNA expression of interferon gamma, TNF-alpha and granzyme B were dose-dependently down-regulated by rMgTX.

CONCLUSIONSKv1.3 channels of peripheral CD4(+)T cell and CD28(null)/CD28(+)T cells from ACS patients significantly increased after activation and Kv1.3-specific channel blocker rMgTX could effectively abolish this effect suggesting a potential role of Kv1.3 channel blocker on plaque stabilization in ACS patients.

Acute Coronary Syndrome ; blood ; metabolism ; CD28 Antigens ; metabolism ; CD4-Positive T-Lymphocytes ; metabolism ; Female ; Humans ; Kv1.3 Potassium Channel ; metabolism ; Lymphocyte Activation ; Male ; Middle Aged ; Patch-Clamp Techniques ; T-Lymphocyte Subsets ; metabolism