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Objective To investigate the myocardial protection effect of dexmedetomidine hydrochloride during off-pump coronary artery bypass graft surgery. Methods Forty patients undergoing off-pump coronary artery bypass grafting were randomly divided into two groups:control group (group C) and dexmedetomidine group (group D).Dexmedetomidine hydrochlo-ride was given at a loading dose of 0. 5 μg?kg-1 to patients in group D, and then infused continuously at a rate of 0.5 μg?kg-1?h-1.The same amount of saline was given to patients in group C. After loading dosing,general anesthesia was per-formed with TCI technique.Trans-esophagus Doppler monitoring was conducted to monitor the blood volume and heart function, and close monitoring of fluid infusion to maintain stable circulation.Invasive blood pressure and heart rate were recorded every 5 min. Blood samples were taken for detection of cTnI,CK-MB,TNF-αand IL-6 contents at the following time points:after induction ( t0 ) ,before operation ( t1 ) ,after operation ( t2 ) ,12 h postoperation ( t3 ) and 24 h postoperation ( t4 ) . Results The blood pressure and heart rate decreased significantly at t0 and t1 in group D compared with group C,and there were no significant differ-ences in the two indexes at other time points between the two groups.Blood CK-MB,cTnI and inflammation factors TNF-α,IL-6 were much higher at t2,t3,t4 than at t0 and t1 in both groups(P<0.05).They were significantly decreased at t2,t3,t4 in group D relative to group C (P<0.05).Vessel active medicines were less given after the operation in group D (P<0.05). Conclusion Dexmedetomidine hydrochloride can mitigate the inflammation responses caused by off-pump coronary artery bypass grafting,re-duce the myocardial injury and improve the cardiac function of the patients.
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Objective To detect the expressions of nerve growth factor (NGF) and its receptors tyrosine kinase A (TrkA) as well as p75 neurotrophin receptor (p75NTR) in the lesions of lichen planus.Methods Biopsy specimens were collected from the lesions of 32 patients with lichen planus and normal skin of 12 healthy human controls and subjected to paraffin embedding.Immunohistochemical avidin-biotin complex (ABC) method was used to detect the expressions of NGF,TrkA and p75NTR.Results NGF and TrkA,which were located in the cytoplasm of keratinocytes,were strongly or moderately expressed in the lesional skin specimens,but absent or weakly expressed in the normal skin specimens (both P ＜ 0.01).No significant differences were observed in the expression of p75NTR between the lesional and normal skin specimens,or in the expressions of NGF,TrkA or p75NTR among specimens from patients in different age groups,patients of different gender or lesions at different sites (all P ＞ 0.05).There was a positive correlation between the expression of NGF and TrkA in the lesions of lichen planus (R2 =0.535,P ＜ 0.01).Conclusion NGF may play a certain role in the development of lichen planus via its highaffinity receptor TrkA.
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Listeria monocytogenes (LM), a Gram-positive facultative intracellular bacterium, can be used as an effective exogenous antigen expression vector in tumor-target therapy. But for successful clinical application, it is necessary to construct attenuated LM stain that is safe yet retains the potency of LM based on the full virulent pathogen. In this study, attenuated LM and recombinants of LM expressing melanoma inhibitory activity (MIA) were constructed successfully. The median lethal dose (LD(50)) and invasion efficiency of attenuated LM strains were detected. The recombinants were utilized for immunotherapy of animal model of B16F10 melanoma. The level of MIA mRNA expression in tumor tissue was detected by using real-time polymerase chain reaction (PCR) with specific sequence, meanwhile the anti-tumor immune response was assayed by flow cytometric analysis and enzyme-linked immunosorbent spot (ELISPOT) assay. The results showed the toxicity and invasiveness of attenuated LM were decreased as compared with LM, and attenuated LM expressing MIA, especially the double-genes attenuated LM recombinant, could significantly induce anti-tumor immune response and inhibit tumor growth. This study implicates attenuated LM may be a safer and more effective vector for immunotherapy of melanoma.
Subject(s)
Animals , Male , Mice , Cancer Vaccines , Genetics , Allergy and Immunology , Extracellular Matrix Proteins , Genetics , Allergy and Immunology , Listeria monocytogenes , Allergy and Immunology , Melanoma , Genetics , Allergy and Immunology , Mice, Inbred C57BL , Vaccines, Attenuated , Genetics , Allergy and ImmunologyABSTRACT
ObjectiveTo investigate the expressions of nerve growth factor (NGF) and its receptors TrkA and p75NTR in dermatofibrosarcoma protuberans and dermatofibroma.MethodsAvidin-biotin immunohistochemical(ABC) method was used to detect the expressions of NGF and its receptors TrkA and p75NTR in paraffin-embedded tissue specimens from 17 cases of DFSP and 15 cases of dermatofibroma.Results NGF and TrkA were highly expressed in both DFSP and dermatofibroma specimens,with no significant difference between the two groups of specimens (x2 =0.11,0.02,respectively,both P ＞ 0.05),while the expression of p75NTR was significantly higher in DFSP than in dermatofibroma specimens(x2 =32,P ＜ 0.01 ).The expression of NGF was positively correlated with that of p75NTR in DFSP(R2 =0.623,P ＜ 0.01 ).ConclusionNGF may play a certain role in the development of DFSP via its high-affinity receptor TrkA and low-affinity receptor p75NTR.
ABSTRACT
Listeria monocytogenes (LM), a Gram-positive facultative intracellular bacterium, can be used as an effective exogenous antigen expression vector in tumor-target therapy. But for successful clinical application, it is necessary to construct attenuated LM stain that is safe yet retains the potency of LM based on the full virulent pathogen. In this study, attenuated LM and recombinants of LM expressing melanoma inhibitory activity (MIA) were constructed successfully. The median lethal dose (LD(50)) and invasion efficiency of attenuated LM strains were detected. The recombinants were utilized for immunotherapy of animal model of B16F10 melanoma. The level of MIA mRNA expression in tumor tissue was detected by using real-time polymerase chain reaction (PCR) with specific sequence, meanwhile the anti-tumor immune response was assayed by flow cytometric analysis and enzyme-linked immunosorbent spot (ELISPOT) assay. The results showed the toxicity and invasiveness of attenuated LM were decreased as compared with LM, and attenuated LM expressing MIA, especially the double-genes attenuated LM recombinant, could significantly induce anti-tumor immune response and inhibit tumor growth. This study implicates attenuated LM may be a safer and more effective vector for immunotherapy of melanoma.
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Objective To investigate the inhibitory effect of live-attenuated Listeria monocytogenes (LM)-based vaccines expressing the gene encoding a melanoma differentiation antigen,MART-1,on malignant melanoma and their mechanism.Methods The constructed plasmid pERL3-MART-1 was used to transform live-attenuated LM by electroporation to construct recombinant LM.i.e.△inlB LM-MART-1 and △actA/△inlB LM-MART-1.The half lethal dose (LD50) of attenuated listeria strains was determined by concentration gradient dilution method.C57BL/6 mice were randomly divided into three groups,namely PBS group,△inlB LM-MART-1 group and △actA/△inlB LM-MART-1 group.Mice were inoculated by intraperitoneal injection of O.1 LD50 of each rLM strain or PBS only.One week later,the mice were injected subcutaneously with 1×105 B16F10 cells(a mouse melanoma cell strain)in 200μl of PBS.Reimmunization was performed on day 14 and 21.Subsequently,the growth of tumor and survival of tumor bearing mice were observed.All mice were killed on day 28,and tumor tissue as well as splenocytes were obtained from these mice for the detection of MART-1 gene expression by real-time quantitative PCR and the percentage of CD4+CD25+T cell by flow cytometry.Results The recombinant △inlB LM-MART-1 and △actA/△inlB LM-MART-1 were constructed successfully.The LD50 of △inlB LM and △actA/△inlB LM was lower than LM-EGDe by 100 and 10 000 times respectively.Compared with PBS,the tumor growth was inhibited with △inlB LM-MART-1 by 46.95%(F=6.3,P<0.05),and by 83.96% with △actA/△inlB LM-MART-1(F=37.8,P<0.01).The relative expression level of MART-1 in △inlB LM-MART-1 group and △actA/△inlB LM-MART-1 group was 8.988±0.207 and 11.315±0.445 times that in PBS group (both P<0.05).The percentage of CD4+CD25+T cells in splenocytes was (2.52±0.20)%,(1.14±0.13)% and (0.44±0.15)% in PBS group,△ialB LM-MART-1 group and △actA/△inlB LM-MART-1 group,respectively;the differences were statistically significant between the three groups (all P<O.01).Conclusions The attenuated LM carrying MART-1 gene has a lower virulence than LM reference strain,and could efficiently suppress the growth of melanoma and lengthen the survival of melanoma-beating mice.
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Objective To investigate the inhibitory effects of L. monocytogenes expressing melanomainhibiting activity(MIA)gene on malignant melanoma.Methods The plasmid pERL3-hly-MIA was constructed and used to transform live L.monocytogenes by electroporation.Atier culture.the transformed L.monocytogenes,namely LM-hly-MIA,was harvested for the detection of MIA protein by Westem Blot.A total of 24 mice were divided into three groups,namely control group,LM group and LM-hly-MIA group,to be immunized with physiological saline,L.monocytogenes and LM-hly-MIA,respectively.One day after the immunization.mice were subcutaneously inoculated with 0.1 mL of B16 cells at a concentration of 1×107/mL.One week later.reimmunization was performed.The size and weight of tumors were observed and measured in these mice.Results Enzyme digestion and Western blot confirmed the Successful construction of plasmid pERL3-hly-MIA.The average weight of tumors in mice was 4.33±0.91 gram.3.36 ±0.41 gram and 1.89±0.52 gram,respectively in the control group,LM group and LM-hly-MIA group,respectively(P＜0.05).with the inhibition rates of tumor growth being 22.4%and 61.5%in LM group and LM-hly-MIA group.respectively.Conclusion The attenuated strain of L.monocytogenes expressing MIA gene could evidently inhibit melanoma growth.