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1.
Zhonghua Nei Ke Za Zhi ; 52(10): 829-32, 2013 Oct.
Artigo em Zh | MEDLINE | ID: mdl-24378059

RESUMO

OBJECTIVE: To investigate the effect of selective phosphodiesterase (PDE) 4 inhibitors on nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNFα) and interleukin-8 (IL-8) secreted by peripheral blood mononuclear cells (PBMCs) in patients diagnosed as rheumatoid arthritis with interstitial lung disease (RA-ILD). METHODS: PBMCs isolated from 15 healthy volunteers (group A) and 20 patients with untreated active RA-ILD (group B) were cultured in vitro. PBMCs from healthy subjects were considered as normal control. PBMCs from RA-ILD patients were divided into four groups with different treatment: blank group (B1), theophylline group (B2), selective PDE4 inhibitor rolipram group (B3), and glucocorticoid group (B4) with dexamethasone. The expression of NF-κB was determined by immunocytochemical staining, and the levels of TNFα and IL-8 in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: (1) The activity of NF-κB and the levels of TNFα and IL-8 in group B1 were significant higher than that in group A (P < 0.01). Compared with group B1, three parameters above were similar to those in group B2 (P > 0.05), while group B3 and group B4 had significant decreased levels of three parameters (P < 0.01); IL-8 level in group B4 was significantly lower than that in group B3 (P < 0.05). (2) TNFα and IL-8 levels were positively correlated with NF-κB activity in group B (r = 0.902 and 0.735, P < 0.01 respectively). (3) The reduction of TNFα and IL-8 levels were positively correlated with reduction of NF-κB activity after intervention of rolipram in group B3 (r = 0.874, P < 0.01; r = 0.561, P < 0.05 respectively). CONCLUSION: NF-κB activation and proinflammatory cytokines were involved in the pathogenesis of RA-ILD. selective PDE4 inhibitors may inhibit the production of inflammatory cytokines by inhibiting the activity of the transcription factor NF-κB in PBMC, thus inhibiting the inflammatory reaction of RA-ILD.


Assuntos
Artrite Reumatoide/sangue , Interleucina-8/metabolismo , Doenças Pulmonares Intersticiais/sangue , Subunidade p50 de NF-kappa B/metabolismo , Inibidores da Fosfodiesterase 4/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Idoso , Artrite Reumatoide/complicações , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Doenças Pulmonares Intersticiais/complicações , Masculino , Pessoa de Meia-Idade
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 32(2): 103-6, 2009 Feb.
Artigo em Zh | MEDLINE | ID: mdl-19567180

RESUMO

OBJECTIVE: To investigate the effect of controlled mechanical ventilation (CMV) on the diaphragm of rats, and therefore to understand the theoretic basis of difficulty weaning due to dysfunction and morphology in diaphragm induced by inappropriate mechanical ventilation. METHODS: Twenty-four adult male SD rats were randomly assigned into 3 experimental groups: a control group, a 18 h CMV group, and a 24 h CMV group. Trans-diaphragmatic pressure (Pdi), maximal trans-diaphragmatic pressure (Pdimax), diaphragm electromyogram (EMGdi), and diaphragm muscle force were measured during CMV at various stimulation frequencies. Morphological changes of the diaphragm myofibril were observed by transmission electron microscopy. Myosin heavy chain (MHC) isoform expression were analyzed with SDS-glycerol PAGE and Western blotting. RESULTS: The Pdimax in the 18 h CMV group and the 24 h CMV group [(8.98+/-0.55, 6.12+/-0.53) cm H2O, 1 cm H2O=0.098 kPa] was significantly reduced (F=82.35, P<0.01) compared with the control group [(14.92+/-0.16) cm H2O]. The Fc and the H/L decreased significantly. At the stimulation frequency of 100 Hz, the diaphragm muscle force in the 18 h CMV group and 24 h CMV group [(84.11+/-0.43) N, (52.65+/-0.64) N, respectively] decreased compare with the control [(98.13+/-0.50) N, F=15.02, P<0.01]. The proportion of MHC2A decreased in the 24 h group compared with control. The ultrastructural changes of the diaphragm was observed in the 24 h CMV group, such as disrupted myofibrils, increased numbers of lipid vacuoles in the sarcoplasm, and abnormally small mitochondria containing focal membrane disruptions. CONCLUSION: Short-term CMV induced diaphragm fatigue and altered the function and morphology of diaphragm in SD rats. Diaphragmatic dysfunction induced by CMV maybe one of the important reasons for difficult weaning.


Assuntos
Diafragma/fisiologia , Diafragma/fisiopatologia , Respiração Artificial , Animais , Masculino , Músculo Esquelético/fisiologia , Músculo Esquelético/fisiopatologia , Ratos , Ratos Sprague-Dawley
3.
Zhonghua Jie He He Hu Xi Za Zhi ; 32(3): 177-81, 2009 Mar.
Artigo em Zh | MEDLINE | ID: mdl-19575935

RESUMO

OBJECTIVE: To investigate the effect of montelukast (MK) on airway inflammation and remodeling in asthmatic rats, and to explore the regulating role of MK on vascular endothelial growth factor (VEGF) and its receptors. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into 3 groups, a control group (n = 8), an asthmatic group (n = 8) and a MK treated group (n = 8). The rats were sensitized with ovalbumin and AL (OH3), and repeatedly exposed to aerosolized ovalbumin. Airway reactivity of the animals were measured by animal lung function meter. VEGF levels and leukotriene D(4) (LTD(4)) in serum were measured by enzyme linked-immunosorbent assay (ELISA). The pathologic changes of bronchi and the lung tissue were evaluated, and the expression of VEGF and its acceptors was analyzed with immunohistochemistry. The vascular counts and vascular smooth muscle thickness were measured by using image analysis system. RESULTS: The bronchial provocation test showed that, in the asthmatic group, the average expiratory resistance increased remarkably. The serum levels of VEGF and LTD(4) in the asthmatic group were 31 +/- 6 and 11 +/- 4 respectively, significantly higher than those in the control group (17 +/- 5 and 6.1 +/- 0.7) respectively and in the MK group (15 +/- 4 and 9.8 +/- 1.6) respectively. (F 63.78, 39.56 all P < 0.01). Immunohistochemistry showed that, the expression of VEGF, VEGFR(1) and VEGFR(2) in the asthmatic group were increased, as compared to those in the control group and the treated group. The vascular counts were 14 +/- 2, 22 +/- 2 and 16 +/- 4 in the control, the asthmatic, and the treated groups. CONCLUSIONS: VEGF and its receptors were over-expressed in the sensitized rat model, and involved in angiogenesis and airway remodeling. MK may be effective in reducing allergic airway inflammation and airway remodeling through VEGF and VEGFR.


Assuntos
Acetatos/farmacologia , Asma/metabolismo , Antagonistas de Leucotrienos/farmacologia , Quinolinas/farmacologia , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Acetatos/uso terapêutico , Remodelação das Vias Aéreas , Animais , Asma/tratamento farmacológico , Ciclopropanos , Antagonistas de Leucotrienos/uso terapêutico , Leucotrieno D4/sangue , Masculino , Neovascularização Patológica , Quinolinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Sulfetos , Fator A de Crescimento do Endotélio Vascular/sangue
4.
Zhonghua Nei Ke Za Zhi ; 43(9): 661-4, 2004 Sep.
Artigo em Zh | MEDLINE | ID: mdl-15500777

RESUMO

OBJECTIVE: To evaluate the hemodynamic effects and cardiac troponin I (cTn I), creatine kinase-MB (CK-MB), myoglobin (Mb) releasing kinetics of acute experimental pulmonary embolism of pigs. METHODS: Sixteen juvenile pigs, of either gender and weighing 30 to 40 kg were studied, 8 in the embolism group and 8 in the control group. The 8 embolism animals received 0.1 g/kg polystyrene beads (diameter range 0.65 to 0.67 mm) suspended in 0.9% saline by venous injection. Pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), pulmonary capillary wedged pressure (PCWP), cardiac output (CO), blood gases and serum cTn I, CK-MB, and Mb were measured before and immediately, 30 min, 1 hour, 2 hour, and 3 hour after acute pulmonary embolism. RESULTS: PAP was increased to 2 - 3 fold of the baseline and the control level immediately, and then decreased to the baseline level in 2 to 3 hours. Serum cTn I and Mb increased significantly after embolism and remained at a higher level through the 3 hour experimental procedure. The CK-MB was not changed after acute pulmonary embolism. CONCLUSIONS: Acute pulmonary embolism caused lung gas exchange abnormality and acute pulmonary hypertension. The hemodynamic effects of acute pulmonary embolism include injury to the myocardial cells and releasing of cTn I and Mb to blood stream. cTn I can be detected in the early phase of acute pulmonary embolism, and maybe a useful marker in diagnosis and management of acute pulmonary embolism.


Assuntos
Mioglobina/sangue , Embolia Pulmonar/fisiopatologia , Troponina I/sangue , Doença Aguda , Animais , Gasometria , Creatina Quinase Forma MB/sangue , Modelos Animais de Doenças , Feminino , Hemodinâmica , Masculino , Embolia Pulmonar/sangue , Suínos
5.
Zhonghua Jie He He Hu Xi Za Zhi ; 27(11): 731-4, 2004 Nov.
Artigo em Zh | MEDLINE | ID: mdl-15634381

RESUMO

OBJECTIVE: To explore the changes of the platelet function and serum anticardiolipin antibody (ACA) in patients with pulmonary thromboembolism (PTE). METHODS: Forty-eight patients with PTE diagnosed by spiral computed tomographic pulmonary angiography (CTPA) were included as the trial group, while 20 person in which PTE was excluded served as the control group. P-selectin, and GPIIb/IIIa expressed on platelets were measured by flow cytometry, and plasma TXB(2), 6-Keto-PGF1alpha, vWF, D-dimer and serum ACA were measured by ELISA and the changes of these parameters were compared 1 week later. RESULTS: In the trial group, the levels of P-selectin, GPIIb/IIIa, TXB(2), vWF, D-dimer and T/K were significantly higher than those in the control group (P < 0.01). But the plasma level of 6-Keto-PGF1alpha in the patients with PTE was significantly lower than that in the control group (P < 0.01). The levels of ACA-IgG and ACA-IgA were significantly higher than those in the control group (P < 0.01). After therapy the level of 6-Keto-PGF1alpha was significantly higher than that before therapy (P < 0.01), and other parameters were significantly lower than those before therapy (P < 0.01). P-selectin, GPIIb/IIIa and vWF were positively correlated with D-dimer (P < 0.01). CONCLUSION: Endothelium damage, platelet activation and hypercoagulation combined with fibrinolytic activation occur in patients with PTE.


Assuntos
Anticorpos Anticardiolipina/sangue , Plaquetas/fisiologia , Embolia Pulmonar/sangue , 6-Cetoprostaglandina F1 alfa/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Endotélio Vascular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/biossíntese , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/imunologia , Tromboxano B2/sangue
6.
Zhonghua Jie He He Hu Xi Za Zhi ; 27(5): 320-3, 2004 May.
Artigo em Zh | MEDLINE | ID: mdl-15196341

RESUMO

OBJECTIVE: To observe the changes of thromboxane B(2) (TXB(2)), 6-keto-prostaglandin F1alpha (6-K-PGF1alpha) and anticardiolipin antibody (ACA) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) before and after institution of nasal continuous positive airway pressure (nCPAP). METHODS: Sixty cases of OSAHS confirmed by polysomnography (PSG) were selected as the trial group, and 20 normal donors without OSAHS were recruited as the control group. Nineteen patients with severe OSAHS were treated by nCPAP. Plasma levels of TXB(2), 6-K-PGF1alpha were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma (serum) level of TXB(2) (ACA) was significantly higher in patients with moderate to severe OSAHS than that in control group (P < 0.01), and nCPAP therapy decreased its level significantly (P < 0.01). Plasma level of 6-K-PGF1alpha was significantly lower than that in the control group (P < 0.01), and nCPAP therapy increased its level significantly (P < 0.01). TXB(2) and ACA were correlated positively with AHI, and negatively with minimal oxygen saturation (P < 0.01). 6-K-PGF1alpha was correlated negatively with AHI, and positively with minimal oxygen saturation (P < 0.01). CONCLUSIONS: The results indicate that patients with OSAHS are susceptible to thromboembolism disease. TXB(2), 6-K-PGF1alpha, ACA may be associated with the high prevalence of thromboembolism in patients with OSAHS. nCPAP therapy is effective in correcting TXB(2), 6-K-PGF1alpha, ACA.


Assuntos
6-Cetoprostaglandina F1 alfa/sangue , Anticorpos Anticardiolipina/sangue , Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono/terapia , Tromboxano B2/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/sangue , Tromboembolia/prevenção & controle
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