To study the antiarrhythmic effect of the newly developed alpha/beta-blocker TJ0711, a variety of animal models of arrhythmia were induced by CaCl2, ouabain and ischemia/reperfusion. Glass microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of arrhythmia induced by CaCl2 was significantly prolonged by TJ0711 at 0.75, 1.5 and 3 mg x kg(-1) doses. TJ0711 (1.5 and 3 mg x kg(-1)) can significantly shorten the ventricular tachycardia (VT) and ventricular fibrillation (VF) duration, the incidence of VF and mortality were significantly reduced. On ischemia-reperfusion-induced arrhythmic model, TJ0711 (0.25, 0.5, 1 and 2 mg x kg(-1)) can significantly reduce the ventricular premature contraction (PVC), VT, VF incidence, mortality, arrhythmia score with a dose-dependent manner. At the same time, rats serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities decreased significantly by TJ0711 (1 and 2 mg x kg(-1)). Ouabain could cause arrhythmia in guinea pigs, when TJ0711 (0.375, 0.75, 1.5 and 3 mg x kg(-1)) was given, the doses of ouabain inducing a variety of arrhythmia PVC, VT, VF, cardiac arrest (CA) were significantly increased with a dose-dependent manner. In the TJ0711 0.1-30 micromol x L(-1) concentration range, guinea pig right ventricular papillary muscle action potential RP (rest potential), APA (action potential amplitude) and V(max) (maximum velocity of depolarization) were not significantly affected. APD20, APD50 and APD90 had a shortening trend but no statistical difference with the increase of TJ0711 concentration. TJ0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high calcium animal arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by TJ0711. APD20, APD50 and APD90 were shortened by TJ0711 at high concentration. Its antiarrhythmic action mechanism may be besides the action of blocking beta1 receptor, may also have a strong selective blocking action on alpha1 receptor and reducing intracellular calcium concentration.
Action Potentials ; drug effects ; Adrenergic alpha-Antagonists ; administration & dosage ; pharmacology ; Adrenergic beta-Antagonists ; administration & dosage ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; administration & dosage ; pharmacology ; Arrhythmias, Cardiac ; blood ; chemically induced ; etiology ; pathology ; physiopathology ; Calcium Chloride ; Creatine Kinase ; blood ; Dose-Response Relationship, Drug ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Lactate Dehydrogenases ; blood ; Male ; Myocardial Reperfusion Injury ; complications ; Myocytes, Cardiac ; drug effects ; physiology ; Ouabain ; Papillary Muscles ; cytology ; Phenoxypropanolamines ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective To explore the influence of Azithromycin on helper T lymphocyte cell(Th)1/Th2 in peripheral blood of children with bronchitic asthma.Methods Twenty-four asthmatic children and 20 healthy children were selected.Peripheral blood mononuclear cells (PBMC) were isolated from venous blood and made into cells suspension in aseptic condition.0.2 mg/L,0.1 mg/L,0.05 mg/L and 0 mg/L Azithromycin were added into the cultures in asthmatic group.The control group was not interfered with Azithromycin.The supernatant was collected after 48 h.The levels of IFN-?,IL-4 and IL-10 in the supernatant were determined by enzyme-linked immunosobent assay(ELISA).SPSS 11.5 software was used to analyze data.Results 1.The level of IL-4 produced from PBMC of asthmatic group was significantly higher than that of control group(P0.05).2.Azithromycin 0.1 mg/L more promoted the secretion of IL-4 than the other 3 concentrations(Pa0.05).3.Azithromycin 0.2 mg/L and 0.1 mg/L more increased the level of IL-10 than the control group(P0.05).Conclusions The routine drug level of Azithromycin(0.1 mg/L) had no effects on the imbalance of Th1/Th2 of asthmatic children,but could modulate the immunological function by up-regulating the level of IL-10.

Objective To investigate the expression of HIF-1α and P-gp protein in pancreatic carcinoma and determine their clinicopathological significance and the correlation between the expression of HIF-1α, P-gp and the clinical prognosis. Method In samples from 74 cases of pancreatic carcinoma and 10 healthy individuals, the expression of HIF-1α and P-gp were detected by immunohistochemical method. Results The positive expression rate of HIF-1α and P-gp was 75.7% and 86.5%,respectively, which were remarkably higher than that in normal pancreatic tissue (P＜0.05). There was a positive correlation between the expression of HIF-1α and that of P-gp. The aberrant expression of HIF-1α and P-gp was associated with lymph node metastasis but not the location, size, clinical stages and nerve invasion of the tumor. Patients with high intensity of HIF-1α and P-gp expression showed a significantly lower median survival time than those with low intensity expression.Conclusions The expression of HIF-1α and P-gp is up-regulated in pancreatic carcinoma and there is a positive correlation between them. The expression of HIF-1α and P-gp might be related to the lymph node metastasis and poor prognosis.

Objective To analyze effects of antithymocyte globulin(ATG) in preventing the occurrence of graft-versus-host disease(GVHD) in allogeneic stem cells transplantation. Methods Twenty-seven patients with leukemia were divided into two groups.The source of the transplantation donor and the type of acute leukemia were similar between the two groups,including HLA-sibling donors,HLA-unrelated donors and HLA-haploidentical donors.The 12 patients in group A adopted the classic method(CsA + MTX) to prevent GVHD.The 15 patients in group B adopted CsA + MTX +ATG to prevent the occurrence of GVHD. Results The 15 patients in group B have been all survived.Four of them presented Ⅱ0 acute GVHD(aGVHD),while the rest 11 patients only presented Ⅰ0 GVHD in approximately 30 d after transplantation with control very soon.In group A,Ⅳ? ultra-acute GVHD occurred in 3 HLA-haploidentical patients at day 7,9 and 10 after transplantation.One HLA-unrelated patient presented Ⅲ? aGVHD.The 4 patients above mentioned died due to pulmonary infection secondary to severe GVHD.The rest 8 HLA-sibling patients presented Ⅱ?-Ⅲ? aGVHD. ConclusionUsing ATG before allogeneic stem cells transplantation can efficiently prevent the occurrence of GVHD or relieve its severity.It can significantly diminish the transplantation related mortality rate.

Objective To investigate the antitumor therapeutic effect of combined therapy of magnetic induction heating by nano-magnetic particles, herpes simplex virus thymidine kinase gene(HSV-tk suicide gene) and internal radiation in mice bearing MCF-7 breast carcinoma. Methods The transfection reagents, plasmids heat shock protein-HSV-tk (pHSP-HSV-tk), ferroso-ferric oxide nano-magnetic fluid flow and 188Re-ganciclovir-bovine serum albumin-nanopaticles (GCV-BSA-NP) were prepared. The heating experiments in vivo were carried out using ferroso-ferric oxide nano-magnetic fluid flow. Sixty mice tumor models bearing MCF-7 breast carcinoma were established and randomly divided into six groups. Group A was the control group, B was gene transfection therapy group, C was hyperthermia group, D was gene transfection therapy combined with radionuclide brachytherapy group, E was gene therapy combined with hyperthermia group, and F was gene therapy, hyperthermia combined with radionuclide brachytherapy group. The tumor growth, tumor mass and histopathological changes were evaluated. The expression of HSV-tk in the groups of B, D, E and F was detected by RT-PCR. Poisson distribution and one-way analysis of variance (ANOVA) were used for statistical analysis by SPSS 10.0 software. Results In the animal heating experiments, the temperature of tumor increased up to 39.6 ℃, 43.2 ℃, and 48.1 ℃ quickly with different injected doses (2, 4 and 6 mg respectively) of nano-magnetic particles and maintained for 40 min. The temperature of tumor tissue reduced to 36.8 ℃, 37.5 ℃ and 37.8 ℃ in 10 min when alternating magnetic field (AMF) stopped. The tumor mass in Groups C ((452.50 ±30.29) mg), D ((240.98 ±35.32)mg), E((231.87 ±27.41) mg) and F ((141.55 ±23.78) mg) were much lower than that in Group A ((719.12±22.65) mg) (F=800.07, P＜0. 01), with the most significant treatment effect in Group F.The tumor mass in Group B((684.05 ±24.02) mg) was higher than that in Group D (t =32. 805, P ＜0. 05). Semi-quantitative RT-PCR analysis showed that the expression of HSV-tk in Groups B and D (0.33 ±0. 13 and 0. 46 ±0.12) was significantly different from that in Groups E and F (0.66 ±0.13 and 0.74 ±0. 11)(F = 21. 573, P ＜ 0.05). Conclusion Combined use of hyperthermia, gene therapy and radionuclide brachytherapy could effectively depress the growth of MCF-7 breast carcinoma, thus possessing treatment potential for this tumor.

Objective To observe the sub-chronic effects of low doses of arsenic poisoning in rabbits exposed to different periods on some of the serum enzymes and biochemical indicators, and to provide the basis for screening of meaningful hematologic indicators for early diagnosis of arsenic poisoning. Methods Twelve adult rabbits,weighing 2.0 - 3.5 kg, were randomly divided into four groups, 3 in each group, and they were fed with drinking water containing sodium arsenite 0(control),0.01,0.05,0.25 mg/L, respectively. Serum alanine aminotransferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), γ-glutamyl transacylase (y-GT), total protein(TP), albumin(ALB), globulin(GLP), and ALB/GLP of rabbit were measured by SYSMEX-180 automated biochemistry analyzer after 8 weeks and 12 weeks exposure. Results The results showed that ALT in 0.05 mg/Lgroup of 12 week[(60.00 ± 4.14)U/L]increased significantly compared with the control[(41.50 ± 2.12)U/L, P ＜0.05];AST in 0.25 mg/L group of 8 week and 12 week[(46.50 ± 3.21 ), (52.33 ± 3.81 )U/L]increased significantly compared with the control[(21.33 ± 3.53), (29.50 ± 3.23 )U/L, all P ＜ 0.05];ALP in 0.05 mg/L and 0.25 mg/L group of 12 week [(78.68 ± 4.85 ), ( 103.00 ± 7.83 ) U / L]increased significantly compared with the control [(45.50 ± 5.50)U/L, all P ＜ 0.05];γ-GT in 0.05 mg/L group of 12 week[(19.33 ± 7.50)U/L]increased significantly compared with the contro1[(8.50 ± 3.53)U/L, P＜ 0.05]. TP, ALB, GLP, ALB/GLP of different groups of 8 week and 12 week were not significantly different statistically(F= 0.77,0.02,0.16,3.14 and 0.51,0.29,0.41,0.52, all P ＞ 0.05). Conclusions Zero point zero five mg/L and higher doses of sub-chronic arsenic exposure has some major damage to the liver. Compared with other serum enzymes and the biochemical indexes, serum AST is a early sensitive indicator of liver injury of the arsenic poisoning.

Objective : To investigate the prevalence of comorbid chronic obstructive pulmonary disease (COPD) and osteoporosis (OP) and its influencing factors among residents aged 40 years and older in Zhangjiagang City, Jiangsu Province, so as to provide insights into prevention of comorbid COPD and OP. Methods: Permanent residents aged 40 years and older were sampled using a multi-stage stratified cluster random sampling method in Zhangjiagang City in 2019, and their pulmonary functions and bone mineral density were measured. The prevalence of comorbid COPD with OP was estimated. The demographic features, smoking, diet, exercises and physical examinations were collected, and factors affecting the prevalence of comorbid COPD with OP were identified using a logistic regression model. Results: Totally 3 140 subjects were enrolled, including 1 315 men (41.88%) and 1 825 women (58.12%), and a mean age of (62.89±9.13) years. A total of 137 subjects were detected with comorbid COPD and OP, with prevalence of 4.36%. The patients with COPD alone included 19 cases with mild, 133 cases with moderate, 87 cases with severe and 26 cases with very severe COPD, and the patients with comorbid COPD and OP included 10 cases with mild, 56 cases with moderate, 56 cases with severe and 15 cases with very severe COPD. The grade of pulmonary functions was higher in patients with comorbid COPD and OP than in patients with COPD alone (Z=-12.304, P<0.001). Multivariable logistic regression analysis identified ages of 65 years and older (OR=2.703, 95%CI: 1.862-3.923), women (OR=2.897, 95%CI: 1.915-4.384) and physical labor (OR=1.540, 95%CI: 1.083-2.189) as factors affecting the development of comorbid COPD and OP. Conclusion The prevalence of comorbid COPD and OP was 4.36% among residents at ages of 40 years and older in Zhangjiagang City, and moderate and severe degree was the predominant grade of pulmonary functions. The elderly, women and physical labors are at a high risk of developing comorbid COPD and OP.

Objective:To investigate the alteration of delayed memory and its relationship with neurogenesis and angiogenesis in vascular dementia (VD) rats after moxibustion therapy. Methods: Two hundred adult male SPF Wistar rats were chosen for the experiment. Thirty-six rats were randomly selected as the sham operation group. Except for rats in the sham operation group (n=36), the others were made into VD models by bilateral common carotid arteries occlusion (BCCAo). After modeling, the 108 survived rats were randomly divided into 3 groups: a model group, a neural stem cells (NSCs) plus endothelial progenitor cells (EPCs) moxibustion group and a NSCs moxibustion group. Co-transplanted implant was transplanted into the rats in the NSCs plus EPCs moxibustion group, and the rats in the NSCs moxibustion group were transplanted by NSCs only. The NSCs plus EPCs moxibustion group and the NSCs moxibustion group received suspended moxibustion therapy at Baihui (GV 20), Dazhui (GV 14) and Shenting (GV 24), (each group was divided into 3 subgroups by the treatment course as 1, 2 and 3 courses). Every group was measured by Morris water maze to evaluate its delayed memory after 3 treatment courses and the rat’s brain was taken out after perfusion of 4% paraformaldehyde one day after 1, 2 and 3 treatment courses, respectively. Marker protein expression was detected by laser confocal microscope to analyze the effect on neurogenesis and angiogenesis. Results: VD rats showed delayed memory in Morris water maze test 3 d after ischemic injury. After 3 courses of moxibustion therapy, VD-induced delayed memory deficits were improved in the NSCs plus EPCs moxibustion group and the NSCs moxibustion group. The expressions of nestin, doublecortin (DCX) and CD34 increased significantly in the two moxibusiton groups after every treatment course (all P＜0.05), which might contribute to the neurogenesis and angiogenesis in hippocampus. In addition, compared with the rats in the NSCs moxibustion group, the expressions of nestin, DCX and CD34 increased significantly in the NSCs plus EPCs moxibustion group (P＜0.05). Conclusion: Moxibustion can reverse VD-induced delayed memory deficits, which may be related to the promotion of neurogenesis and angiogenesis.

BACKGROUNDRetroviral vectors have been widely used to introduce foreign into various target cells in vitro, thus showing relatively high systemic delivery efficiency of various transgene products. The authors investigated the stability and efficiency of skeletal muscle-specific hybrid retroviral vectors in expression of human factor IX (FIX) in vitro and iv vivo.

METHODSFIX cDNA in LIXSN vector was replaced with a FIX minigene containing splicing donor and splicing acceptor sequence of first intron of human FIX gene. Two copies of muscle creatine kinase enhancer (MCK, Me2) were inserted in forward or reverse orientation at NheI site of 3' long terminal repeat (LTR), resulting in two hybrid vectors, which were designated as LMe2IXm2SN(F) and LMe2IXm2SN(R), respectively. The vectors were tested in vitro and in vivo for stability and muscle-specificity of factor IX expression with SCID mice.

RESULTSMuscle cells carrying vector with Me2 expressed significantly higher levels of FIX (up to 1800 ng/106.24 h) than those without Me2, thus suggesting that Me2 could specifically increase expression level of FIX in muscle cells. Myoblasts transduced with LMe2IXm2SN(R) produced much less FIX in vivo in SCID mice than LMe2IXm2SN(F). One or two copies of Me2 sequence were deleted in myoblasts transduced with LMe2IXm2SN(R) without changing the orientation of Me2.

CONCLUSIONSLTR inserted with MCK enhancers can specifically increase human FIX expression in skeletal muscle cells in vitro and in vivo, and MCK enhancer should be positioned in the same orientation as that of LTR promoter.

Animals ; Creatine Kinase ; genetics ; Creatine Kinase, MM Form ; Enhancer Elements, Genetic ; Factor IX ; analysis ; genetics ; Gene Expression ; physiology ; Genetic Techniques ; Genetic Vectors ; Hybridization, Genetic ; Isoenzymes ; genetics ; Mice ; Mice, SCID ; Retroviridae ; genetics ; Terminal Repeat Sequences

Based on single factor tests,the optimum vacuum belt drying conditions of Qibai Pingfei granule were obtained through Box-Benhnken central combination design and RSM. In this study, drying time, drying temperature and extract density were chosen as independent variables, while transferring rate ginsenoside Rg₁, Re, Rb₁and astragaloside IV were taken as dependent variables. The optimum parameters are as follows: drying time of 112 min, drying temperature of 87 °C and extract density of 1.30 g · mL⁻¹. At the optimum condition, transferring rate ginsenoside Rg₁+ Re, Rb₁and astragaloside IV were 88.01%, 87.31%, 84. 34%. Above all, the optimum processing parameters of vacuum belt drying of Qibai Pingfei granule is reasonable and feasible, which can provide reliable basis for production.
Chemistry, Pharmaceutical ; instrumentation ; methods ; Desiccation ; instrumentation ; methods ; Drugs, Chinese Herbal ; chemistry ; Plants, Medicinal ; chemistry ; Quality Control ; Temperature ; Vacuum