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1.
Curr Med Sci ; 42(4): 785-796, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35788944

ABSTRACT

OBJECTIVE: It has been reported that intrinsic apoptosis is associated with the progression of bladder cancer (BC). Recent evidence suggests that polyribonucleotide nucleotidyltransferase 1 (PNPT1) is a pivotal mediator involved in RNA decay and cell apoptosis. However, the regulation and roles of PNPT1 in bladder cancer remain largely unclear. METHODS: The upstream miRNA regulators were predicted by in silico analysis. The expression levels of PNPT1 were evaluated by real-time PCR, Western blotting, and immunohistochemistry (IHC), while miR-183-5p levels were evaluated by qPCR in BC cell lines and tissues. In vitro and in vivo assays were performed to investigate the function of miR-183-5p and PNPT1 in apoptotic RNA decay and the tumorigenic capability of bladder cancer cells. RESULTS: PNPT1 expression was decreased in BC tissues and cell lines. Overexpression of PNPT1 significantly promoted cisplatin-induced intrinsic apoptosis of BC cells, whereas depletion of PNPT1 potently alleviated these effects. Moreover, oncogenic miR-183-5p directly targeted the 3' UTR of PNPT1 and reversed the tumor suppressive role of PNPT1. Intriguingly, miR-183-5p modulated not only PNPT1 but also Bcl2 modifying factor (BMF) to inhibit the mitochondrial outer membrane permeabilization (MOMP) in BC cells. CONCLUSION: Our results provide new insight into the mechanisms underlying intrinsic apoptosis in BC, suggesting that the miR-183-5p-PNPT1 regulatory axis regulates the apoptosis of BC cells and might represent a potential therapeutic avenue for the treatment of BC.


Subject(s)
MicroRNAs , Urinary Bladder Neoplasms , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation , Cisplatin/pharmacology , Exoribonucleases , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Mitochondrial Proteins , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics
2.
China Tropical Medicine ; (12): 850-2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-980027

ABSTRACT

@#Abstract: Objective To investigate the diagnostic efficacy of rifampin-resistant real-time fluorescent quantitative nucleic acid amplification detection technology (GeneXpert MTB/RIF) in bronchoalveolar lavage fluid (BALF) combined with peripheral blood tuberculosis infection T cell spot test (T-SPOT) and tuberculosis antibody (TB-Ab) in smear-negative pulmonary tuberculosis. Methods The clinical data of 114 cases of clinically diagnosed smear-negative pulmonary tuberculosis, 80 cases of non-tuberculous pulmonary diseases and 22 cases of smear-positive pulmonary tuberculosis in our hospital from January 2019 to January 2021 were retrospectively analyzed. The detection results of peripheral blood T-SPOT, TB-Ab and BALF GeneXpert in the three groups were analyzed. The sensitivity, specificity, negative predictive value, positive predictive value, false negative rate, false positive rate and Youden index of the three detection methods were compared. The differences in the positive detection rate of smear-negative pulmonary tuberculosis between the separate detection and the combined detection of the three methods were compared. The receiver operating characteristic curve (ROC) was performed to calculate the area under the curve (AUC). Results The sensitivity of BALF GeneXpert and peripheral blood T-SPOT and TB-Ab was 66.91%, 80.88% and 90.44%, respectively. The specificity was 98.75%, 73.75% and 41.25%, respectively; the diagnostic coincidence rates were 78.70%, 78.24% and 72.22%, respectively, which were higher than 70.00%. In the smear-negative pulmonary tuberculosis group, the positive detection rates of these three methods in the smear-negative pulmonary tuberculosis group were 63.15%, 79.82% and 90.35%, respectively, and the differences were statistically significant compared with those in the non-tuberculosis pulmonary disease group (all P<0.01). The positive detection rate of the three combined methods in the smear-negative pulmonary tuberculosis group was 96.49 %, which was significantly higher than that of TB-GeneXpert method and T-SPOT, and the differences were statistically significant (χ2=37.283, P<0.01; χ2=13.612, P<0.01); the Youden index of combined detection was significantly higher than that of single detection, and the AUC of combined detection was 0.977, which was significantly higher than that of single detection. Conclusion BALF GeneXpert combined with peripheral blood T-SPOT and TB-Ab can significantly improve the diagnostic rate of bacterial-negative pulmonary tuberculosis, providing a strong basis for guiding clinical treatment.

3.
J Huazhong Univ Sci Technolog Med Sci ; 37(6): 873-879, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29270746

ABSTRACT

Combined hepatocellular-cholangiocarcinoma (CHC) is a mixed tumor containing elements of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Its remarkable histological heterogeneity has been linked to putative hepatic progenitor cell (HPC) origin. However, detailed histological or phenotypic description is rarely documented. In the present study, we reassessed 68 cases previously diagnosed as hepatitis B-related CHCs by immunohistochemistry and double-fluorescence immunostaining, focusing on HPC associated phenotypic observation of intermediate area of the tumor. It was found that tumor cells showed remarkable heterogeneity in intermediate area. Tumor cells with intermediate morphology between hepatocytes and cholangiocytes were oval-shaped and small with scant cytoplasm and hyperchromatic nuclei, arranging in solid nests mostly. By Keratin 7 (K7) staining, it appeared that the nests of tumor cells represented a maturation process from the undifferentiated small cells to mature hepatocytes through the "transitional" cells. Then, these small cells were further confirmed with intermediate phenotype as HPC by exploring immature hepatocellular marker and HPC/biliary markers co-localization. In conclusion, the HPC associated trait in CHC can be interpreted by HPC origin or gain of "stemness" by dedifferentiation. It is still too soon to give a final word that it is innate or acquired signature of HPC associated trait in CHC.


Subject(s)
Bile Duct Neoplasms/pathology , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/pathology , Cholangiocarcinoma/pathology , Hepatitis B/pathology , Liver Neoplasms/pathology , Adult , Aged , Antigens, Tumor-Associated, Carbohydrate/blood , Antigens, Tumor-Associated, Carbohydrate/genetics , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/virology , Bile Ducts, Intrahepatic/pathology , Bile Ducts, Intrahepatic/surgery , Bile Ducts, Intrahepatic/virology , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/virology , Cell Dedifferentiation , Cholangiocarcinoma/genetics , Cholangiocarcinoma/surgery , Cholangiocarcinoma/virology , Female , Hepatitis B/genetics , Hepatitis B/surgery , Hepatitis B/virology , Hepatocytes/pathology , Hepatocytes/virology , Humans , Immunohistochemistry , Keratin-7/genetics , Keratin-7/metabolism , Liver/pathology , Liver/surgery , Liver/virology , Liver Neoplasms/genetics , Liver Neoplasms/surgery , Liver Neoplasms/virology , Male , Middle Aged , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/virology , Phenotype , Retrospective Studies , alpha-Fetoproteins/genetics , alpha-Fetoproteins/metabolism
4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-333411

ABSTRACT

Combined hepatocellular-cholangiocarcinoma (CHC) is a mixed tumor containing elements of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC).Its remarkable histological heterogeneity has been linked to putative hepatic progenitor cell (HPC) origin.However,detailed histological or phenotypic description is rarely documented.In the present study,we reassessed 68 cases previously diagnosed as hepatitis B-related CHCs by immunohistochemistry and double-fluorescence immunostaining,focusing on HPC associated phenotypic observation of intermediate area of the tumor.It was found that tumor cells showed remarkable heterogeneity in intermediate area.Tumor cells with intermediate morphology between hepatocytes and cholangiocytes were oval-shaped and small with scant cytoplasm and hyperchromatic nuclei,arranging in solid nests mostly.By Keratin 7 (K7) staining,it appeared that the nests of tumor cells represented a maturation process from the undifferentiated small cells to mature hepatocytes through the "transitional" cells.Then,these small cells were further confirmed with intermediate phenotype as HPC by exploring immature hepatocellular marker and HPC/biliary markers co-localization.In conclusion,the HPC associated trait in CHC can be interpreted by HPC origin or gain of"stemness" by dedifferentiation.It is still too soon to give a final word that it is innate or acquired signature of HPC associated trait in CHC.

5.
Biosci Rep ; 35(4)2015 Jul 20.
Article in English | MEDLINE | ID: mdl-26193886

ABSTRACT

While insulin is an anabolic hormone, AMP-activated protein kinase (AMPK) is not only a key energy regulator, but it can also control substrate metabolism directly by inducing skeletal muscle protein degradation. The hypothesis of the present study was that insulin inhibits AMPK and thus down-regulates the expression of the ubiquitin E3 ligases, muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) in skeletal muscle cells. Differentiated L6 myotubes were treated with 5-aminoimidazole-4-carboxamide-1-ß-4-ribofuranoside (AICAR) and/or compound C to stimulate and/or block AMPK respectively. These treatments were also conducted in the presence or absence of insulin and the cells were analysed by western blot and quantitative real-time PCR. In addition, nucleotide levels were determined using HPLC. The activation of AMPK with AICAR enhanced the mRNA levels of MAFbx and MuRF1. Insulin reduced the phosphorylation and activity AMPK, which was accompanied by reduced MAFbx and MuRF1 mRNA levels. Using a protein kinase B (PKB/Akt) inhibitor, we found that insulin regulates AMPK through the activation of Akt. Furthermore, insulin down-regulated AMPK α2 mRNA. We conclude that insulin inhibits AMPK through Akt phosphorylation in L6 myotubes, which may serve as a possible signalling pathway for the down-regulation of protein degradation. In addition, decreased expression of AMPK α2 may partially participate in inhibiting the activity of AMPK.


Subject(s)
AMP-Activated Protein Kinases/biosynthesis , Down-Regulation/drug effects , Gene Expression Regulation, Enzymologic/drug effects , Insulin/pharmacology , Muscle Fibers, Skeletal/enzymology , Ubiquitin-Protein Ligases/biosynthesis , Aminoimidazole Carboxamide/analogs & derivatives , Animals , Cell Line , Muscle Fibers, Skeletal/cytology , Muscle Proteins/metabolism , Rats , Ribonucleotides/biosynthesis , SKP Cullin F-Box Protein Ligases/metabolism , Tripartite Motif Proteins , Ubiquitin-Protein Ligases/metabolism
6.
J Cancer Res Clin Oncol ; 140(7): 1159-70, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24752339

ABSTRACT

PURPOSE: To assess the beneficial and harmful effects of transarterial embolization (TAE) or transarterial chemoembolization (TACE) for curative resection of hepatocellular carcinoma (HCC). METHODS: The authors conducted an extensive search of studies on this strategy. All randomized controlled trials comparing TACE or TAE plus operation versus operation only were considered for inclusion, regardless of blinding, language, or publication status. Results were performed with disease-free survival (DFS) and overall survival (OS) as the primary endpoint. Tumor response and adverse events were secondary endpoints. RESULTS: A total of 10 studies involving 909 HCC participants finally fulfilled the predefined inclusion criteria. Four trials assessed preoperative TACE versus control and six trials assessed postoperative TACE versus control. There were significant improvements for DFS [HR 0.62 (95 % CI 0.49-0.79)] and OS [HR 0.60 (0.46-0.79)] in the postoperative TACE compared with the control when the mean tumor size was bigger than 5 cm. However, preoperative TACE did not improve DFS [HR 0.92 (0.71-1.20)] and OS [HR 1.07 (0.78-1.46)] for curative resection of HCC. Substantial differences in criteria for assessing tumor response did not allow quantitative analyses. Fever (26.7-85.9 %), abdominal pain (19.3-71.2 %), and nausea/vomiting (27.4-66.3 %) were common adverse events. Relatively rare but more serious complications were also reported. CONCLUSIONS: Postoperative TACE offers potential benefits for curative resection of HCC when the mean tumor size is bigger than 5 cm.


Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Liver Neoplasms/therapy , Carcinoma, Hepatocellular/mortality , Chemoembolization, Therapeutic/adverse effects , Embolization, Therapeutic/adverse effects , Embolization, Therapeutic/methods , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Humans , Liver Neoplasms/mortality , Postoperative Complications/epidemiology , Randomized Controlled Trials as Topic/statistics & numerical data , Survival Analysis
7.
Hepatol Res ; 44(3): 259-69, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23607290

ABSTRACT

AIM: Available published work on the benefit of adjuvant antiviral therapy after curative treatment of hepatocellular carcinoma (HCC) reports controversial results. The objective of this systematic review was to evaluate the effect of adjuvant antiviral therapy on recurrence and survival after curative treatment of HCC. METHODS: We conducted an extensive search strategy. All randomized controlled trials comparing adjuvant antiviral therapy versus placebo or no treatment were considered for this review. Results were expressed as hazard ratio for time-to-event outcomes with 95% confidence intervals using RevMan 5. RESULTS: We included nine trials (three of low risk of bias and six of unclear risk of bias) with 954 patients. All the included studies used conventional interferon (IFN) as adjuvant antiviral therapy; none of them used pegylated IFN or nucleoside analogs. There were significant improvements for recurrence-free survival and overall survival in the adjuvant IFN group compared with the control group. Subgroup analysis also showed a significant difference favoring IFN therapy in hepatitis C virus (HCV)-related HCC patients, but for hepatitis B virus (HBV)-related patients, the difference failed to reach statistical significance. A dose reduction was needed in 28.3% of patients and discontinuation of IFN therapy happened in 8.2% of patients due to moderate to severe side-effects. CONCLUSION: Our study suggested potential benefits of adjuvant IFN therapy following curative treatment of HCC, especially for HCV-related HCC. Further high-quality randomized controlled trials of more effective adjuvant antiviral regimens, either used alone or in combination, for virus-related HCC, especially HBV-related HCC, are needed.

8.
Shock ; 40(4): 297-302, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23364430

ABSTRACT

Burn-blast combined injury has a complex pathological process that may cause adverse complications and difficulties in treatment. This study aims to establish a standard animal model of severe burn-blast combined injury in rats and also to investigate early phasic changes of blood coagulation. By using 54 Wistar rats, distance from explosion source (Hexogen) and size of burned body surface area were determined to induce severe burn-blast combined injury. Thereafter, 256 rats were randomly divided into four groups (n = 64): blast injury group, burn injury group, burn-blast combined injury group, and sham injury group. Gross anatomy and pathological changes in lungs were investigated at 3, 24, 72, and 168 h, respectively. Blood was also collected for analyzing coagulation parameters as prothrombin time, activated partial thromboplastin time, and plasma levels of fibrinogen, D-dimer, antithrombin III, and α2-antiplasmin from 0 to 168 h after injury. Severe burn-blast combined injury was induced by inflicting rats with a moderate blast injury when placing rats 75 cm away from explosion source and a full-thickness burn injury of 25% total body surface area. The rats with burn-blast combined injury had more severe lung injuries when compared with the other three groups. Pathological examination in the BBL group showed diffused alveolar hemorrhage, fluid filling, alveolar atelectasis, rupture and hyperplasia of partial alveolar septum, emphysema-like change, reduced capillary bed, and infiltration of extensive polymorphonuclear cells after injury. The blood of combined injured rats was in a hypercoagulable state within 24 h, shortly restored from 24 to 48 h, and rehypercoagulated from 48 to 72 h after injury. A secondary excessively fibrinolytic function was also found thereafter. The rat model of burn-blast combined injury was successfully established by simulating real explosion characteristics. Rats with burn-blast combined injuries suffered from more severe lung injuries and abnormal coagulation and fibrinolytic function than those induced by a burn injury or a blast injury component. Hence, a time-dependent treatment strategy on coagulation function should be emphasized in clinical therapy of burn-blast combined injury.


Subject(s)
Blast Injuries/blood , Blast Injuries/complications , Blood Coagulation , Burns/blood , Burns/complications , Animals , Blast Injuries/pathology , Burns/pathology , Disease Models, Animal , Fibrinolysis , Lung/pathology , Lung Injury/blood , Lung Injury/pathology , Male , Rats , Rats, Sprague-Dawley
9.
Burns ; 39(4): 745-53, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22999209

ABSTRACT

OBJECTIVE: Neutrophil elastase (NE) takes part in the pathogenesis of acute lung injury. However, its role in lung injury of burn-blast combined injury is unclear. Our objective was to assess the role of NE, and effect of sivelestat, a specific NE inhibitor, in lung injury induced by burn-blast combined injury in rats. METHODS: One hundred and sixty male Sprague-Dawley rats were randomly subjected to burn-blast combined injury (BB) group, burn-blast combined injury plus sivelestat treatment (S) group or control (C) group. Blood gas, protein concentration and NE activity in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity, serum concentrations of TNF-α and IL-8, etc. were investigated from 0 h to 7 d post-injury. RESULTS: In BB group, PaO2 decreased, while NE activity in BALF, total protein concentration in BALF, pulmonary MPO activity and W/D ratio, serum concentrations of TNF-α and IL-8 increased with neutrophil infiltration, progressive bleeding and pulmonary oedema. Compared with BB group, sivelestat treatment decreased the NE activity and ameliorated the above indexes. CONCLUSION: Sivelestat, exerts a protective effect in lung injury after burn-blast combined injury through inhibiting NE activity to decrease pulmonary vascular permeability, neutrophil sequestration, and production of TNF-α and IL-8.


Subject(s)
Blast Injuries/complications , Burns/complications , Leukocyte Elastase/physiology , Lung Injury/enzymology , Animals , Blast Injuries/drug therapy , Blast Injuries/enzymology , Bronchoalveolar Lavage Fluid/chemistry , Burns/drug therapy , Burns/enzymology , Carbon Dioxide/metabolism , Disease Models, Animal , Glycine/analogs & derivatives , Glycine/therapeutic use , Interleukin-8/metabolism , Lung Injury/drug therapy , Lung Injury/etiology , Male , Oxygen/metabolism , Partial Pressure , Proteinase Inhibitory Proteins, Secretory/therapeutic use , Rats , Rats, Sprague-Dawley , Serine Proteinase Inhibitors/therapeutic use , Sulfonamides/therapeutic use , Tumor Necrosis Factor-alpha/metabolism
10.
World J Gastroenterol ; 18(23): 2938-47, 2012 Jun 21.
Article in English | MEDLINE | ID: mdl-22736917

ABSTRACT

AIM: To investigated the interaction between toll-like receptor 4 (TLR4)-activated hepatoma cells and macrophages in the induction of tumor-immune suppression mediated by CD4+CD25(high) family of transcription factor P3 (FOXP3) regulatory T cells (Tregs). METHODS: The proportion of FOXP3+ Tregs was identified in peripheral blood and tumor tissues of 60 hepatocellular carcinoma (HCC) patients. TLR4 expression was examined in tumor tissues and cell lines. The correlation was examined between FOXP3+ Tregs in peripheral blood and TLR4 expression of HCC tissues. Following activation of TLR4 in H22 murine hepatoma cells pre-incubated with lipopolysaccharide (LPS) and co-cultured with macrophage cell line RAW246.7, the synthesis of cytokines tumor necrosis factor-α, CCL22, and interleukin (IL)-10 by the two cell lines was detected and analyzed. RESULTS: FOXP3+ Tregs were enriched in tumor sites, and circulating FOXP3+ Tregs were increased in HCC patients in correlation with multiple tumor foci and up-regulated TLR4 expression in HCC tissues. Semi-quantitative analysis indicated that TLR4 was over-expressed in HCC compared with the matched normal tissues. Cell cultivation experiments indicated that the mRNAs of IL-10 and CCL22 were significantly up-regulated in the RAW246.7 cell line when co-cultured with LPS pre-incubated H22 cells. CONCLUSION: In hepatoma cell lines, TLR4 may indirectly facilitate the recruitment of Tregs to the tumor site and promote intrahepatic metastasis through its interaction with macrophages.


Subject(s)
Carcinoma, Hepatocellular/immunology , Liver Neoplasms/immunology , Macrophages/immunology , T-Lymphocytes, Regulatory/metabolism , Toll-Like Receptor 4/metabolism , Adolescent , Adult , Aged , Animals , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Chemokine CCL22/biosynthesis , Female , Forkhead Transcription Factors/metabolism , Humans , Immunosuppression Therapy , Interleukin-10/biosynthesis , Liver Neoplasms/blood , Liver Neoplasms/metabolism , Lymphocyte Count , Macrophages/metabolism , Male , Mice , Middle Aged , RNA, Messenger/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , Young Adult
11.
Front Med China ; 4(4): 457-62, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21191748

ABSTRACT

This study was performed to determine the prognostic role of preoperative serum carbohydrate antigen (CA) 19-9 levels in the survival of patients with cholangiocarcinoma. Articles published up to June 1(st), 2010 that evaluated preoperative CA19-9 levels and the prognosis of cholangiocarcinoma were collected for meta-analysis. The required information for calculating individual relative risk (RR) was extracted from the studies, and a combined overall RR was estimated. Nine eligible studies were included. One study dealt with extra-hepatic cholangiocarcinoma, while the other eight studies analyzed intra-hepatic cholangiocarcinoma. The mean methodological quality score was 74.1%, ranging from 65.5% to 82.5%. The overall RR for the nine studies was 1.28 (95% confidence interval = 1.10-1.46), and the Z-score for overall effect was 13.83 (P<0.001). The association between serum CA19-9 level and lymph node involvement was also assessed. The combined RR was 1.471 (95% confidence interval = 0.411-5.264) and Z-score for overall effect was 0.59 (P = 0.553). CA19-9 levels were associated significantly with the prognosis of patients with cholangiocarcinoma. This meta-analysis shows that elevation of preoperative CA19-9 levels is correlated with a poor prognosis of patients with cholangiocarcinoma. However, larger scale and randomized studies are needed to draw a more substantive conclusion.


Subject(s)
Bile Duct Neoplasms/blood , Bile Duct Neoplasms/mortality , Bile Ducts, Intrahepatic , CA-19-9 Antigen/blood , Cholangiocarcinoma/blood , Cholangiocarcinoma/mortality , Bile Duct Neoplasms/surgery , Cholangiocarcinoma/surgery , Humans , Prognosis , Risk , Treatment Outcome
12.
Zhonghua Yi Xue Za Zhi ; 90(24): 1707-10, 2010 Jun 22.
Article in Chinese | MEDLINE | ID: mdl-20979883

ABSTRACT

OBJECTIVE: To explore the early changes in serum neutrophil elastase (NE) in rats with burn, blast injury or combined burn-blast injury and its significance. METHODS: A total of 176 male Sprague Dawley rats were randomly divided into four groups: control (C), burn (BU), blast injury (BL) and burn-blast combined injury (BB). Rats in C group were not injured. Animals in BU group were subjected to 25% TBSA full-thickness burn on back with 94 degrees C water for 12 seconds; Animals in BL group were inflicted with moderate blast injury with 5 g 8701 compressed dynamite stick as the explosion source 75 cm away while left chest facing the explosive source; Rats in BB group were burned immediately after the blast injury similarly as in BL group. During the first 24 h post-injury, animals in BU and BB groups received intraperitoneal injection of sodium lactate Ringer's solution at a dose of 50 ml x kg(-1) x 12 h(-1). Protein concentration in bronchoalveolar lavage fluid (BALF), water content of lung tissue and NE content in serum were determined at 0 h (C group), 3 h, 6 h, 12 h, 1 d, 2 d, 3 d, 7 d post-injury. RESULTS: Protein concentration in BALF, water content of lung tissue and NE content in serum in SD rats of the injured groups were significantly higher than those in C group (P < 0.01 or P < 0.05), peaked within 2 d post-injury, especially at 2 d post-injury (NE content in serum: BU group, 319. 85 +/- 19.50 ng/ml; BL group, 467.43 +/- 31.64 ng/ml; BB group, 626.00 +/- 26.38 ng/ml vs. C group, 78.53 +/- 25.10 ng/ml). Overall, protein concentration in BALF, water content of lung tissue and NE content in serum in BB group were significantly higher than BU and BL groups (P < 0.01 or P < 0.05). Correlation analysis showed that within 3 d postinjury, a significant positive correlation was found between the protein concentration in BALF, water content of lung tissue and NE content in serum (r = 0.7910, 0.8078, P < 0.05) in BU group. NE content in serum and protein concentration in BALF were significantly positively correlated in BB group (r = 0.8672, P < 0.05). CONCLUSION: NE may play an important role in early lung injury of burn or blast injury, especially in combined burn-blast injury.


Subject(s)
Burns/blood , Leukocyte Elastase/blood , Lung Injury/blood , Wounds and Injuries/blood , Animals , Disease Models, Animal , Male , Rats , Rats, Sprague-Dawley
13.
Zhonghua Shao Shang Za Zhi ; 26(1): 37-40, 2010 Feb.
Article in Chinese | MEDLINE | ID: mdl-20510032

ABSTRACT

OBJECTIVE: To investigate the characteristics and differences of propofol pharmacokinetics in shock phase and hypermetabolic phase in severe burn in rabbits. METHODS: Twenty New Zealand rabbits were assigned to burn group (n = 10) and sham injury group (n = 10) according to the random number table. Rabbits in burn group were inflicted with 30%TBSA full-thickness scald (named burn below), resuscitated instantly, and were intravenously injected with 5.1 mg/kg propofol 6 hours after injury. 1.5 mL blood was collected from left external jugular vein at 1, 3, 5, 10, 15, 20, 30, 45, 60, 90 minute(s) after injection respectively. Above procedure was performed again 1 week later. Rabbits in sham injury group were treated similarly as rabbits in burn group but were sham scalded. Propofol concentration in plasma was determined with high performance liquid chromatography. Data of propofol concentration-time were analyzed with 3P97 practical pharmacokinetics calculating program, and then the most fit compartment model was selected to calculate pharmacokinetic parameters. RESULTS: The blood concentration-time curve of propofol fitted in with the two-compartment model in burn group, and three-compartment model in sham injury group. During shock phase, comparing with central compartment distribution volume [Vc, (3.1 + or - 1.5) L/kg], area under curve [AUC, (25 + or - 7) mg x min x L(-1)], elimination phase half life [t1/2beta, (113 + or - 93) min], clearance [CLs, (110 + or - 50) mL x kg(-1) x min(-1)] of rabbits in sham injury group, Vc[(8.8 + or - 4.2) L x kg(-1)] and AUC [(44 + or - 10) mg x min x L(-1)] increased significantly (with t value respectively 3.191 and 3.668, and P values both below 0.01); t1/2beta [(339 + or - 258) min] prolonged (t = 2.932, P < 0.05); CLs [(40 + or - 30) mL x kg(-1) x min(-1)] decreased (t = -3.013, P < 0.05) in burn group. During hypermetabolic phase, CLs [(180 + or - 40) mL x kg(-1) x min(-1)] of rabbits in burn group was significantly higher than that in sham injury group [(90 + or - 30) mL x kg(-1) x min(-1), t = -3.013, P < 0.05]. Comparing with those of rabbits in burn group during shock phase, Vc [(4.1 + or - 1.3) L/g] and AUC [(24 + or - 5) mg x min x L(-1)] decreased significantly (with t value respectively 2.979 and 3.766, and P value both below 0.01); distribution phase half time [t1/2alpha, shock phase (16.1 + or - 13.1) min and hypermetabolic phase (8.3 + or - 2.5) min] and t1/2beta [(55 + or - 19) min] shortened obviously (with t value respectively 9.065 and 8.795, and P values both below 0.01); CLs increased significantly (t = 4.238, P < 0.01) during hypermetabolic phase. CONCLUSIONS: There are great differences in propofol pharmacokinetics between shock phase and hypermetabolic phase in severely burned rabbits. The change is characterized by increase in Vc and AUC, extension of t1/2alpha and t1/2beta, decrease in CLs during shock phase and obvious increase of CLs during hypermetabolic phase.


Subject(s)
Burns/metabolism , Propofol/pharmacokinetics , Shock/metabolism , Animals , Burns/pathology , Rabbits
14.
Zhonghua Zhong Liu Za Zhi ; 29(4): 249-52, 2007 Apr.
Article in Chinese | MEDLINE | ID: mdl-17760248

ABSTRACT

OBJECTIVE: To explore the eukaryotic expression of arresten in CHO cells and to investigate its basic biological activities. METHODS: CHO cells were divided into three groups: transfected pSecTag-arresten group, transfected pSecTag group and control group without transfection. PSecTag-arresten was transfected into CHO cells by Lipofectamine 2000 method. The arresten mRNA in CHO cells was assayed by RT-PCR. The protein expression of arresten gene was examined by Western-Blot. The cells expressing arresten were screened out by Zeocin. The effect of arresten on huvec cell migration and anchoring to three-dimensional vascular structures was measured. RESULTS: The result of RT-PCR and Western-blot showed that arresten gene has been successfully transfected into CHO cells and expressed in those cells. Arrssten inhibited huvec cell migration and anchoring to three-dimensional vascular structures. CONCLUSION: CHO cells expressing arresten have been obtained successfully. Arresten can inhibit huvec cell migration and anchoring to three-dimensional vascular structures, indicating that it might be one of its anti-angiogenetic approaches.


Subject(s)
Angiogenesis Inhibitors/biosynthesis , Angiogenesis Inhibitors/pharmacology , Cell Movement/drug effects , Collagen Type IV/biosynthesis , Endothelial Cells/drug effects , Angiogenesis Inhibitors/genetics , Animals , Blotting, Western , CHO Cells , Cell Line , Cells, Cultured , Collagen Type IV/genetics , Collagen Type IV/pharmacology , Cricetinae , Cricetulus , Endothelial Cells/cytology , Endothelial Cells/physiology , Humans , Neovascularization, Physiologic/drug effects , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Transfection
15.
World J Gastroenterol ; 9(4): 843-6, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12679945

ABSTRACT

AIM: To investigate the safety, rationality and the practicality of enteral nutritional (EN) support in the postoperative patients with damaged liver function and the protective effect of EN on the gut barrier. METHODS: 135 patients with liver function of Child B or C grade were randomly allocated to enteral nutrition group (EN, 65 cases), total parenteral nutrition group (TPN, 40 cases) and control group (CON, 30 cases). Nutritional parameters, hepatic and kidney function indexes were measured at the day before operation, 5th and 10th day after the operation respectively. Comparison was made to evaluate the efficacy of different nutritional support. Urinary concentrations of lactulose(L) and mannitol(M) were measured by pulsed electrochemical detection(HPLC-PED) and the L/M ratio calculated to evaluate their effectiveness on protection of gut barrier. RESULTS: No significant damages in hepatic and kidney function were observed in both EN and TPN groups between pre- and postoperatively. EN group was the earliest one reaching the positive nitrogen balance after operation and with the lowest loss of body weight and there was no change in L/M ratio after the operation (0.026+/-0.004) at the day 1 before operation, 0.030+/-0.004 at the day 5 postoperative and 0.027+/-0.005 at the day 10 postoperative), but the change in TPN group was significant at the day 5 postoperative (0.027+/-0.003 vs 0.038+/-0.009,P<0.01). CONCLUSION: EN is a rational and effective method in patients with hepatic dysfunction after operation and has significant protection effect on the gut barrier.


Subject(s)
Enteral Nutrition , Liver Diseases/complications , Parenteral Nutrition, Total , Postoperative Period , Adult , Carcinoma, Hepatocellular/complications , Cholangiocarcinoma/complications , Chronic Disease , Humans , Liver Function Tests , Liver Neoplasms/complications , Treatment Outcome
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