AIMTo observe the effects of hypercapnia on nuclear factor-kappaB and TNF-alpha in acute lung injury models.

METHODSSix of the twenty-two healthy New Zealand white rabbits were randomly allocated to control group (Group C), the other sixteen rabbits were injected with oleic acid (0.1 ml/kg) intravenously, then were randomized to normocapnic group (Group N, n = 8) versus hypercapnic group (Group H, n = 8). TNF-alpha of serum and bronchoalveolar lavage fluid (BALF) and the expression of nuclear factor-kappaB in the lung were analyzed after three hours' mechanical ventilation.

RESULTSTNF-alpha of serum and bronchoalveolar lavage fluid in Group N and H was significantly higher than that in Group C (P < 0.01), and that of Group N was higher than that of Group H (P < 0.05). The expression of nuclear factor-kappaB in Group H was less than that in Group N by both immunohistochemistry and Western-blot analysis. Peak airway pressure in Group H was significantly lower than that in Group N and the dynamic lung compliance was significantly higher than that in Group N (P < 0.05). PaO2 in Group H was significantly higher than that in Group N (P < 0.05). Histologic damage in Group N was significantly severer than that in Group H.

CONCLUSIONHypercapnia is protective in this in vivo model of ALl. The mechanisms might be associated with the prohibition of nuclear factor-kappaB and then the decreased expression of TNF-alpha by hypercapnia.

Acute Lung Injury ; metabolism ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Hypercapnia ; metabolism ; NF-kappa B ; blood ; metabolism ; Rabbits ; Tumor Necrosis Factor-alpha ; blood ; metabolism

Animals ; beta Catenin ; Blotting, Western ; Breast Neoplasms ; Breast ; Cell Self Renewal ; Flow Cytometry ; Fluorescent Antibody Technique ; Genome ; Humans ; In Vitro Techniques ; Kinesin ; Luciferases ; Mice ; Neoplasm Metastasis ; Neoplastic Stem Cells ; Prognosis ; Real-Time Polymerase Chain Reaction ; Stem Cells

Objective To explore the Electrocardiography (ECG) changes of residents in Keshan disease area and the status of growth and decline of Keshan disease in Shaanxi Province. Methods Using stratified randomized sampling method,2 mild,2 moderate and 2 serious disease counties were selected respectively in 2005 and 2006. A total of 6 counties were sampled,2 villages,one with severe disease and one with mild,were selected from each sampled county. A total of 12 villages were selected. The clinical examination and ECG were conducted in 3-year old children of agricultural population of the selected villages. Results ECG of 5692 cases were performed in the selected 12 village in the 6 counties,in which 4917 cases showed normal electrocardiogram,up to 86.38% (4917/5692). Two hundred and fifty-two cases showed roughly normal electrocardiograms,up to 4.43%(252/5692). Five hundred and twenty-three cases had abnormal electrocardiogram,accounting for 9.19% (523/5692). Among them,the abnormal electrocardiogram rates in mild,moderate and serious disease areas were 7.07% (144/2036), 11.41%(167/1646) and 10.54%(212/2010),respectively. Atrioventricular block was the major abnormal electrocardiogram change,followed by arrhythmia,ST-T changes,and low voltage. One hundred and thirty-nine cases were confirmed as latent and chronic Keshan diseases. One hundred and thirty-one cases were latent Keshan, and detection rate was 2.30%(131/5692). Eight cases were chronic Keshan,and the detective rate was 0.14% (8/5692). Complete right bundle branch block [37.06% (63/170) ],ST-T changes [22.35% (38/170) ],multiple premature ventricular beats [12.94% (22/170)] were the major abnormal electrocardiogram change of Keshan patients. Conclusions Atrioventricular block and arrhythmia are the major abnormal electrocardiogram changes. Keshan disease incidences are controlled under a stable condition.

Objective To explore the status of Keshan disease in Shaanxi province to provide a scientific basis for decision-making of prevention and control of Keshan disease. Methods Nineteen infected villages were randomly selected in 19 infected counties in the range of Keshan disease infected area in Shaanxi province in 2008 as the investigation sites. Clinical examination and electrocardiography were performed in the chosen people at every spots, chest X-ray of posteroanterior position film in 2-meter distance was taken in suspicious cardiac patients, and determining the selenium contents was also determined in the collected grain samples of the investigators. Results Of the 10 228 investigated residents in the endemic area, 110 Keshan disease patients were detected, the total detection rate was 1.08% (110/10 228). Among the 110 patients, 92 were potential Keshan disease, which accounted 0.90%(92/10 228); 18 chronic Keshan disease formed a detection rate of 0.18%( 18/10 228); no acute and sub-acute type of Keshan disease had been inspected. Potential Keshan disease patients often showed electrocardiogram abnormality of complete fight bundle branch block [48.57%(51/105)], ST-T change[ 19.05% ( 20/105 ) ], frequent premature ventricular contraction [ 10.48 % ( 11/105 ) ], left ventricular hypertrophy [ 5.71% (6/105) ], block in the anterosuperior division of the left branch[5.71%(6/105)]; Chronic of Keshan patients mostly presented atrial fibrillation [ 24.00% (6/25) ], left ventricular hypertrophy [ 20.00% (5/25) ], complete right bundle branch block [ 20.00% (5/25)]. The increase rate of cardiothoracie ratio was 18.08% (32/177). Food samples of wheat, corn, millet and rice in infected area residents were of selenium content, being (0.096± 0.028), (0.089 ±0.029), (0.087 ± 0.016), (0.047 ± 0.016)mg/kg, respectively. Conclusions Keshan disease in Shaanxi province is steadily declining, potential and chronic Keshan diseases are currently the main clinical types. Selenium content of food in endemic area has reached the level of the non-endemic area.

Based upon the underlying mechanism and pathological evidence of tissue injury of antibody-mediated rejection (AMR) , four etiological and symptomatic therapies were proposed for managing AMR, including etiological treatment of AMR including antibody-targeting, B cell or plasma cell-targeting therapies; strategies for preventing antibody-mediated endothelial damage: an inhibition of complement/antibody dependent cell-mediated pathways; anticoagulant & thrombolytic therapies for thrombotic microangiopathy secondary to endothelial damage ; anti-inflammatory therapies for acute/chronic vascular inflammation secondary to endothelial damage. Etiological treatment is essential for preventing and treating AMR while symptomatic measures, such as anticoagulant, thrombolytic and antiinflammatory therapies, are stressed. Finally the authors devised therapeutic strategies for AMR in 4 different patient groups of non-sensitized allograft recipients, sensitized allograft recipients, individuals with active AMR and those with chronic active AMR.

OBJECTIVEGene expression profiling of diffuse large B-cell lymphoma (DLBCL) of different immunophenotypes.

METHODSThe study included 156 cases of DLBCL, which were subclassified by immunohistochemistry including CD10, bcl-6 and MUM1. Affymetrix U133 plus2.0 oligonucleotide microarrays were used to obtain differential gene expression profiling of 9 DLBCL (3 representative cases from each immunophenotypical group) and 3 tonsils. Clinical stages of all 9 lymphomas were Ann Arbor stage IV.

RESULTSThe immunohistochemistry subclassified 156 cases of DLBCL into 3 groups: CD10(+) and/or bcl-6(+), MUM1(-) (group 1); CD10(+) and/or bcl-6(+), MUM1(+) (group 2); CD10(-) and bcl-6(-), MUM1(+) (group 3). By gene expression array, 9 lymphomas and 3 tonsils were clustered in an unsupervised fashion into 4 groups (A, B, C and D), which were in accordance with the immunophenotypical groups (group 1, 2, 3 and normal). A total of 81 genes were markedly decreased and 86 genes were over-expressed in all DLBCL groups. Although Group B lymphomas showed mixed immunophenotypical features of both germinal center B-cell-like DLBCL (Group A) and activated B-cell-like lymphomas (Group C), gene profile clustering showed that Group B was dissimilar to Group A or Group C, with 45 over-expressed and 27 uniquely expressed genes.

CONCLUSIONSGene expression profiling indicates that DLBCL can be subgrouped at the molecular level and can be identified by immunophenotyping. The gene expression profile of Group B lymphomas suggests that factors other than the cell-of-origin may contribute to the pathogenesis of DLBCL.

Aged ; Cluster Analysis ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Immunophenotyping ; methods ; Interferon Regulatory Factors ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; classification ; genetics ; immunology ; pathology ; Middle Aged ; Neprilysin ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Young Adult

OBJECTIVETo determine whether erythropoietin (EPO) promotes rapid proliferation of glioma through Akt pathway.

METHODSWe detected the expression of EPO in human glioma tissues using immunohistochemistry. A nude mouse model bearing human glioma U87 cell xenograft was established and given intraperitoneal injection of EPO or saline every other day, and the tumor growth was observed. In the in vitro experiment, U87 cells were treated with PBS (control), EPO, or EPO with Akt inhibitor, and the expression of p-Akt and cyclin D1 was detected using Western blotting; the cell proliferation rate was determined using cell counting kit-8 and clone formation assay, and the cell cycle changes were analyzed with flow cytometry.

RESULTSCompared with low-grade glioma tissues, high-grade glioma tissues exhibited a significantly increased EPO expression (P=0.0002). In the tumor-bearing mice, EPO treatment significantly increased the expression of EPO (P=0.0006) and p-Akt (P=0.0003) in the tumor and obviously increased the tumor volume (P<0.0001) and weight (P=0.0003). In U87 cells cultured in vitro, EPO treatment obviously accelerated the cell proliferation (P=0.020 on day 3 and 0.028 on day 5), promoted clone formation (P=0.0010), and increased proliferation index (P=0.0028); EPO significantly enhanced the protein expression of p-Akt (P=0.0020) and cyclin D1 (P=0.0022). The application of Akt inhibitor significantly suppressed the effect of EPO in enhancing cyclin D1 and p-Akt expression (both P<0.0001) and promoting cell proliferation.

CONCLUSIONEPO can significantly accelerate the proliferation of glioma through Akt pathway.

The effect of bombesin (BOM) on non-cholinergic excitatory synaptic transmission of the guinea pig inferior mesenteric ganglion (IMG) was investigated by intracellular recording. Repetitive stimulation of the colon nerves (1 ms, 25 Hz, 4 s) elicited a burst of action potentials, which was followed by a long-lasting depolarization in 74.3% (52/70) of the IMG neurons. The depolarization was not blocked by nicotinic (d-tubocurarine, 100 micromol/L) and muscarinic (atropine, 1 micromol/L) antagonists, but was eliminated in a low Ca(2+)/high Mg(2+) Krebs solution, indicating that the depolarization was due to the release of non-cholinergic transmitters. Superfusing the ganglia with BOM (10 micromol/L, 1 min) induced a slow depolarization in 66.5% (109/164) neurons tested. The BOM response was not appreciably changed in low Ca(2+)/high Mg(2+) Krebs solution (n=6, P>0.05), suggesting that BOM depolarized the neurons by acting directly on the postsynaptic membrane rather than via a release of other endogenous depolarizing substances. In a total of 102 cells that exhibited late slow excitatory postsynaptic potential (ls-EPSP), superfusion of the ganglia with BOM produced a membrane depolarization in 82 neurons (80%), while the remaining 20 cells (20%) exhibited no response to BOM. In 18 neurons with ls-EPSP, 4 (22%) neurons were sensitive to both BOM and SP; 6 (33%) and 5 (28%) neurons were only sensitive to BOM and SP, respectively. The remaining 3 (17%) neurons were insensitive to both BOM and SP. Membrane resistance (Rm) had no apparent change in 47.3%, 59.5 % of the neurons tested during the ls-EPSP (n=55) and BOM depolarization (n=84), respectively, but had a marked decrease in 38.2%, 27.4%, and a marked increase in the remaining 14.5%, 13.1% of the neurons. However, when the Rm change accompanying ls-EPSP was compared with that accompanying BOM depolarization (n=20) in the same neuron, the changes in Rm were always parallel. Moreover, ls-EPSP (n=6) and BOM depolarization (n=8) were all augmented by conditioning hyperpolarization. The extrapolated values of the reversal potentials of ls-EPSP and BOM depolarization were 46.0+/-8.0 and 50.0+/-7.0 mV (n=8, P>0.05), respectively. In 14 BOM-sensitive neurons, a ls-EPSP was elicited by repetitive colon nerve stimulation. Superfusion of BOM (10 micromol/L) in these cells initially caused a large depolarization and then membrane potential gradually subsided to resting level in the continuous presence of BOM. Stimulation of the presynaptic nerves at this time failed to elicit a detecable ls-EPSP in 2 neurons and induced a much smaller one in 10 cells, while the ls-EPSP in the remaining 2 neurons was not appreciably affected. On the other hand, prolonged superfusion of BOM had no effect on the amplitude and duration of ls-EPSP in 6 BOM-insensititive neurons studied (P>0.05). The amplitude and duration of SP-induced depolarization were not altered by prolonged superfusion of BOM (n=4, P>0.05) Superfusion of tyr(4) D-phe(12) bombesin (1 micromol/L, 10 15 min), a BOM receptor antagonist, did not cause any noticeable changes in passive membrane properties nor block nicotinic f-EPSPs, but markedly suppressed (n=5) or completely abolished (n=11) BOM depolarization in all 16 neurons tested Similarly, tyr(4) D-phe(12) bombesin partially or completely antagonized the ls-EPSP in 9 out of a total of BOM sensitive neurons (n=11). The ls-EPSP elicited in the remaining two neurons was insignificantly affected by this drug. However, following 10 20 min of wash with Krebs solution the ls-EPSP was reversed. In contrast, superfusion of the ganglia with tyr(4) D-phe(12) bombesin did not change the amplitude and duration (P>0.05) of ls-EPSP in 10 BOM-insensitive cells. Similarly, the amplitude and duration of SP-induced depolarization were not appreciably affected by tyr(4) D-phe(12) bombesin (n=6, P>0.05). In conclusion, our results indicate that BOM may be another transmitter mediating the ls-EPSP in the guinea pig IMG and that there is no cross-desensitization of BOM receptors and SP receptors.
Action Potentials ; drug effects ; physiology ; Animals ; Bombesin ; pharmacology ; Electric Stimulation ; Excitatory Postsynaptic Potentials ; drug effects ; physiology ; Female ; Ganglia, Sympathetic ; drug effects ; physiology ; Guinea Pigs ; In Vitro Techniques ; Male ; Synaptic Transmission ; drug effects

The effect of adventitia on the occurrence and development of atherosclerosis (As) is getting more attentions. Fibroblasts, mast cells, dendritic cells, vasa vasorums, vascular-associated lymphoid tissues, and vascular peripheral nerves are related to the occurrence and development of As. This essay summarizes studies on the changes in adventitia in As process and its effect on the occurrence and development of As, as well as the latest progress.
Adventitia ; drug effects ; metabolism ; pathology ; Animals ; Atherosclerosis ; drug therapy ; metabolism ; pathology ; Disease Progression ; Humans

OBJECTIVETo study possible immunobiological potential of Osmunda japonica Thunb.

METHODSImmunomodulatory effects of ethanol extracts prepared from rhizomes of O. japonica and phenolic compounds isolated from the extracts were investigated under the in vitro conditions using the rat peritoneal cells (2×10(6)/mL; 24 h culture). Biosynthesis of nitric oxide (NO) was assayed by Griess reagent, production of prostaglandin E2 (PGE2) and secretion of cytokines were determined by enzyme-linked immunoabsorbent assay.

RESULTSThe extracts activated dose dependently, with the onset at 2.5-5 μmol/L concentrations, the high output NO production, and secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Mild enhancement of NO was produced by the aldehyde-type phenolics 4-hydroxybenzaldehyde and 3,4-hydroxybenzaldehyde. In contrasts, the acetone-type phenolics 4-hydroxybenzalacetone and 3,4-hydroxybenzalacetone inhibited production of immune mediators including cytokines (TNF-α, IL-1β, IL-6), NO, and PGE2. The 3,4-hydroxybenzalacetone was more effective than 4-hydroxybenzaldehyde. The IC50s estimates ranged within the interval of 5-10 μmol/L. No signs of cytotoxicity were observed up to the 50 μmol/L concentration of the compounds.

CONCLUSIONPhenolic compounds contained in medicinal herb Osmunda japonica possess distinct immunomodulatory activity.

Animals ; Cell Survival ; drug effects ; Cells, Cultured ; Dinoprostone ; biosynthesis ; Female ; Ferns ; chemistry ; Immunologic Factors ; pharmacology ; Interferon-gamma ; pharmacology ; Lipopolysaccharides ; pharmacology ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Peritoneum ; cytology ; drug effects ; Phenols ; chemistry ; isolation & purification ; pharmacology ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Polymyxin B ; pharmacology ; Proline ; analogs & derivatives ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Thiocarbamates ; pharmacology