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1.
Drug Des Devel Ther ; 14: 519-526, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099334

RESUMO

INTRODUCTION: Hesperetin-5,7,3'-O-trimethylether (HTME), a synthetic liposoluble hesperetin, has been reported to be a dual phosphodiesterase (PDE)3/4 inhibitor. We investigated its inhibitory effects on methacholine (MCh)-induced airway hyperresponsiveness (AHR) and its potential for treating atypical asthma and COPD. METHODS: FlexiVent system was used to determine AHR in ovalbumin (OVA) sensitized and challenged mice. Determination of cytokines was performed by using mouse T helper (Th)1/Th2 cytokine CBA kits, and of total immunoglobulin (Ig)E and OVA-specific IgE using ELISA kits. The number of inflammatory cells was counted using a hemocytometer. Xylazine/ketamine-induced anesthesia was to assess nausea, vomiting, and gastric hypersecretion in these mice. RESULTS: HTME dually and competitively inhibited PDE3/4 activities in the Lineweaver-Burk analysis. HTME (30 and 100 µmol/kg) dose-dependently and significantly decreased the airway resistance (RL) and increased lung dynamic compliance (Cdyn) values induced by MCh. It significantly suppressed numbers of total inflammatory cells and neutrophils, and levels of cytokines in bronchoalveolar lavage fluid (BALF). HTME dose-dependently and significantly inhibited total and OVA-specific IgE levels in the BALF and serum. However, HTME did not influence xylazine/ketamine-induced anesthesia. CONCLUSION: HTME exerted anti-inflammatory and bronchodilator effects and may be useful in treating chronic obstructive pulmonary disease and allergic atypical asthma with no gastrointestinal side effects.


Assuntos
Anti-Inflamatórios/farmacologia , Hesperidina/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Hipersensibilidade Respiratória/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Relação Dose-Resposta a Droga , Feminino , Hesperidina/administração & dosagem , Hesperidina/química , Cloreto de Metacolina/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Inibidores de Fosfodiesterase/administração & dosagem , Inibidores de Fosfodiesterase/química , Hipersensibilidade Respiratória/induzido quimicamente
2.
Anal Sci ; 36(6): 739-743, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31932522

RESUMO

A clear and positive correlation between the CO2 concentration and the blood-sugar level has been observed via a non-invasive and time-dependent monitoring of CO2 concentration from human breath, which is carried out by using a home-made gas chromatography (GC)/milli-whistle compact analyzer. The time-dependent sampling of the CO2 concentration correlated between 5.0 to 5.6% (1% = 104 ppm) in accordance with blood-sugar level variations of 80 to 110 mg/dL. The analytical method results in a rapid, continuous and non-invasive determination of blood-sugar level via measurement of the CO2 concentration exhaled from the lungs.


Assuntos
Testes Respiratórios , Dióxido de Carbono/sangue , Açúcares/sangue , Cromatografia Gasosa/instrumentação , Humanos , Fatores de Tempo
3.
Eur J Pharmacol ; 868: 172879, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31863766

RESUMO

Thrombin plays a crucial role in lung inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Thrombin induces the release of interleukin-8 (IL-8)/CXCL8 by lung epithelial cells, and this phenomenon plays a vital role in lung inflammation. Our previous studies have indicated that thrombin stimulates IL-8/CXCL8 expression through PI3K/Akt/IκB kinase (IKK)α/ß/nuclear factor-κB (NF-κB) and p300 pathways in human lung epithelial cells. In the present study, we explored the roles of mammalian target of rapamycin (mTOR) and p70S6 kinase (p70S6K) in thrombin-induced NF-κB activation and IL-8/CXCL8 release in human lung epithelial cells. In this study, we found that rapamycin (an mTOR inhibitor) and p70S6K siRNA diminished thrombin-induced IL-8/CXCL8 release. Thrombin induced mTOR Ser2448 phosphorylation and p70S6K Thr389 phosphorylation in a time-dependent manner. Moreover, rapamycin attenuated thrombin-stimulated p70S6K phosphorylation. We also found that transfection of cells with the dominant negative mutant of Akt (Akt DN) reduced the thrombin-induced increase in mTOR phosphorylation and p70S6K phosphorylation. Moreover, thrombin-stimulated p300 phosphorylation was attenuated by Akt DN, rapamycin, and p70S6K siRNA. Thrombin triggered p70S6K translocation from the cytosol to the nucleus in a time-dependent manner. Thrombin induced the complex formation of p70S6K, p300, and p65; acetylation of p65 Lys310, and recruitment of p70S6K, p300, and p65 to the κB-binding site of the IL-8/CXCL8 promoter region. In conclusion, these results indicate that thrombin initiates the Akt-dependent mTOR/p70S6K signaling pathway to promote p300 phosphorylation and NF-κB activation and finally induces IL-8/CXCL8 release in human lung epithelial cells.


Assuntos
Pulmão/imunologia , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/imunologia , Serina-Treonina Quinases TOR/metabolismo , Trombina/metabolismo , Células A549 , Asma/imunologia , Asma/patologia , Proteína p300 Associada a E1A/metabolismo , Células Epiteliais/imunologia , Células Epiteliais/patologia , Humanos , Interleucina-8/metabolismo , Pulmão/patologia , Fosforilação/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fator de Transcrição RelA/metabolismo
4.
Pharm Biol ; 57(1): 380-384, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31155999

RESUMO

Context: Butylidenephthalide (Bdph) has been reported to inhibit rat uterine contractions, but significantly potentiate the noradrenaline (NA)-induced contractions in guinea-pig vas deferens (GPVDs). Objective: The present study elucidates the binding specificity of Bdph in GPVD to potentiate contractions. Materials and methods: Electrical field stimulation (EFS, supramaximal voltage, 1 ms and 1 Hz) or exogenous NA (50 µM) was applied to the GPVD in Krebs or 1/10 Mg-Tyrode's solution, respectively. After the clonidine (10 nM)-induced twitch inhibition or the exogenous NA-induced contractions reached a constant, Bdph (50 µM) was added 2 min prior to the subsequent addition of NA (50 µM). Three experiments were performed. In the presence of Bdph (100 µM), the release of NA in the medium and remaining NA content in the tissues were determined after EFS-stimulation. Results: Bdph (100 µM) significantly antagonized the clonidine (10 nM)-induced twitch inhibition from 22.5 ± 2.1 to -11.4 ± 1.6% (n = 6) and dibutyryl-cAMP (300 µM) from 25.7 ± 3.2 to 7.9 ± 4.0% (n = 8). Bdph (100 µM) significantly increased the electrically stimulated release of NA from 393.0 ± 109.5 to 1000.0 ± 219.1 ng/g (n = 6). Bdph (50 µM) potentiated the exogenous NA (50 µM)-induced contractions from 3.0 ± 0.06 to 3.9 ± 0.06 g (n = 3), but after washout of Bdph, the response to NA gradually curtailed. Discussion and conclusions: Bdph action may be through the nonspecific binding of the butylidene group to prejunctional α2- and postjunctional α1-adrenoceptors to reversibly block K+ channels, and irreversibly block VDCCs on the smooth muscle cell membrane, respectively.


Assuntos
Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Anidridos Ftálicos/farmacologia , Receptores Adrenérgicos/metabolismo , Ducto Deferente/efeitos dos fármacos , Animais , Canais de Cálcio/metabolismo , Clonidina/farmacologia , Relação Dose-Resposta a Droga , Estimulação Elétrica , Cobaias , Masculino , Músculo Liso/metabolismo , Músculo Liso/fisiopatologia , Norepinefrina/metabolismo , Norepinefrina/farmacologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/antagonistas & inibidores , Ligação Proteica , Ducto Deferente/metabolismo , Ducto Deferente/fisiopatologia
5.
Sensors (Basel) ; 19(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003541

RESUMO

One concern to the patients is the off-line detection of pneumonia infection status after using the ventilator in the intensive care unit. Hence, machine learning methods for ventilator-associated pneumonia (VAP) rapid diagnose are proposed. A popular device, Cyranose 320 e-nose, is usually used in research on lung disease, which is a highly integrated system and sensor comprising 32 array using polymer and carbon black materials. In this study, a total of 24 subjects were involved, including 12 subjects who are infected with pneumonia, and the rest are non-infected. Three layers of back propagation artificial neural network and support vector machine (SVM) methods were applied to patients' data to predict whether they are infected with VAP with Pseudomonas aeruginosa infection. Furthermore, in order to improve the accuracy and the generalization of the prediction models, the ensemble neural networks (ENN) method was applied. In this study, ENN and SVM prediction models were trained and tested. In order to evaluate the models' performance, a fivefold cross-validation method was applied. The results showed that both ENN and SVM models have high recognition rates of VAP with Pseudomonas aeruginosa infection, with 0.9479 ± 0.0135 and 0.8686 ± 0.0422 accuracies, 0.9714 ± 0.0131, 0.9250 ± 0.0423 sensitivities, and 0.9288 ± 0.0306, 0.8639 ± 0.0276 positive predictive values, respectively. The ENN model showed better performance compared to SVM in the recognition of VAP with Pseudomonas aeruginosa infection. The areas under the receiver operating characteristic curve of the two models were 0.9842 ± 0.0058 and 0.9410 ± 0.0301, respectively, showing that both models are very stable and accurate classifiers. This study aims to assist the physician in providing a scientific and effective reference for performing early detection in Pseudomonas aeruginosa infection or other diseases.


Assuntos
Nariz Eletrônico , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Infecções por Pseudomonas/diagnóstico , Adulto , Feminino , Humanos , Unidades de Terapia Intensiva , Aprendizado de Máquina , Masculino , Pneumonia Associada à Ventilação Mecânica/complicações , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pneumonia Associada à Ventilação Mecânica/fisiopatologia , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/fisiopatologia , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/patogenicidade
6.
Pharm Biol ; 56(1): 378-384, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30122096

RESUMO

CONTEXT: The rhizome of Ligusticum chuaxiong Hort. (Umbelliferae) has been used by Chinese for several thousand years. Its main constituent, butylidenephthalide (Bdph), was proved to be active in inhibiting rat uterine contractions induced by prostaglandin F2α and was reported to be a nonspecific antispamodic and a blocker of voltage-dependent Ca2+ channels (VDCCs). OBJECTIVES: The present study investigates the mechanisms of Bdph for twitch facilitation in ICR mouse vas deferens (MVD). MATERIALS AND METHODS: Electrical field stimulation (EFS, supramaximal voltage ranging from 60-90 V, 1 ms, 0.2 Hz) was applied to the isolated MVD in Krebs solution. Interactions between Bdph (50 µM) and calcium antagonist (verapamil, diltiazem or aspaminol) on the EFS-evoked twitch responses were determined. The number of experiments was 3-18. RESULTS: Bdph (50 µM)-induced twitch facilitations from 100 to 391.9% were unrelated to activation of postjunctional cholinergic or adrenergic receptors. Verapamil and Bdph unabolished the twitch facilitation each other. Diltiazem unabolished the Bdph-induced twitch facilitation. In contrast, Bdph abolished those induced by diltiazem. Aspaminol at 20 µM abolished the Bdph-induced twitch facilitation. In contrast, Bdph abolished those induced by aspaminol. Tetraethylammonium and 4-aminopyridine, the K+ channel blockers, significantly augmented the Bdph-induced twitch facilitation. DISCUSSION AND CONCLUSIONS: Bdph may bind to the different, more and same subtypes of VDCCs from verapamil, than diltiazem, and as aspaminol does on prejunctional membrane, respectively. Besides a blocker of VDCCs, Bdph may be a blocker of K+ channels on prejunctional membrane. Thus, Bdph depolarized the membrane and facilitated the cumulative Ca2+-induced twitch responses.


Assuntos
Contração Muscular/efeitos dos fármacos , Anidridos Ftálicos/farmacologia , Ducto Deferente/efeitos dos fármacos , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/fisiologia , Relação Dose-Resposta a Droga , Estimulação Elétrica/métodos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Contração Muscular/fisiologia , Técnicas de Cultura de Órgãos , Ducto Deferente/fisiologia
7.
Eur J Pharmacol ; 786: 47-52, 2016 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-27238973

RESUMO

The naturally occurring and synthetic butylinenephthalide (Bdph) has two geometric isomers. Z- and E-Bdph were reported to have geometric stereoselectivity for voltage-dependent calcium channels (VDCCs) in guinea-pig ileum. The aim of this study was to investigate whether the binding of Z- and E-Bdph on prejunctional VDCCs of rat vas deferens (RVD) is stereoselective. The twitch responses to electrical field stimulation (EFS, supramaximal voltage, 1 ms, 0.2Hz) were recorded on a polygraph. Z- and E-Bdph concentration-dependently inhibited the twitch responses to EFS in full tissue, prostatic portion and epididymal portion of RVD. The pIC50 value of Z-Bdph was greater than that of E-Bdph in the electrically stimulated prostatic portion of RVD, suggesting that the binding of Bdph on the non-adrenergic prejunctional VDCCs of cell membrane is stereoselective. In the prostatic portion, exogenous Ca(2+) only partially reversed the twitch inhibition by Z-Bdph, but effectively reversed those by Ca(2+) channel blockers, such as verapamil, diltiazem and aspaminol, suggesting that the action mechanisms may be different from those of Ca(2+) channel blockers. K(+) channel blockers, such as tetraethylammonium (TEA) and 4-aminopyridine (4-AP), may prolong duration of action potential to allow greater Ca(2+) entry and induced more release of transmitters. Therefore both blockers via their prejunctional actions reversed the twitch inhibition induced by Z-Bdph in all preparations of RVD by a non-specific antagonism.


Assuntos
Canais de Cálcio/metabolismo , Anidridos Ftálicos/química , Anidridos Ftálicos/farmacologia , Próstata , Ducto Deferente/efeitos dos fármacos , Ducto Deferente/metabolismo , 4-Aminopiridina/farmacologia , Animais , Cálcio/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Masculino , Movimento/efeitos dos fármacos , Norepinefrina/farmacologia , Anidridos Ftálicos/metabolismo , Ratos , Estereoisomerismo , Especificidade por Substrato , Tetraetilamônio/farmacologia , Ducto Deferente/citologia , Ducto Deferente/fisiologia
8.
Front Pharmacol ; 7: 75, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27064479

RESUMO

In traditional Chinese medicine (TCM), a combination of kudzu and Chen-Pi is frequently prescribed for relieving colds, fever, bronchitis, and cough. It contains daidzein and hesperetin, selective inhibitors of family 3 (PDE3), and 4 (PDE4) of phosphodiesterases (PDEs), respectively. In passively sensitized human airways, allergen-induced contraction was reported to be inhibited only by the simultaneous inhibition of PDE3 and PDE4, but not by single inhibition of either isozyme. Therefore, we are interested in investigating the interaction between daidzein and hesperetin on their antispasmodic effects in the isolated sensitized and non-sensitized guinea-pig tracheas, to clarify the difference between these two tissues, because effects of TCM prescription on patients with or without allergic asthma are often different. Guinea-pigs were sensitized by subcutaneous injection of ovalbumin (OVA) into legs. After sensitization, the baseline and cumulative OVA-induced contractions of the sensitized trachea were isometrically recorded on a polygraph. In the same way, the histamine (30 µM)-induced tonic contraction of non-sensitized guinea-pig trachea was recorded. The isobole method was used to analyze the antagonism and synergism between daidzein and hesperetin. The isoboles showed antagonism between daidzein and hesperetin on baseline relaxant effect and OVA (100 µg/ml)-induced contraction in the sensitized guinea-pig trachea. In contrast, the isobole showed synergism between daidzein and hesperetin on the relaxant effect of histamine-induced tonic contraction in non-sensitized guinea-pig trachea. These results suggest that the combination of kudzu and Chen-Pi for relieving colds, fever, bronchitis and cough is effective in patients without, but might show little effect in patients with allergic asthma.

9.
BMC Complement Altern Med ; 15: 344, 2015 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-26438097

RESUMO

BACKGROUND: Butylidenephthalide (Bdph), a main constituent of Ligusticum chuanxiong Hort., was reported to have selective antianginal effect without changing blood pressure in conscious rat. Recently, we have observed that Bdph antagonized cromakalim, an ATP-dependent K(+) channel opener, in guinea-pig trachea. Thus, we were interested in investigating whether Bdph at the dose without changing blood pressure antagonized cromakalim-induced systolic pressure reduction in conscious rats. METHODS: Systolic arterial pressures of conscious rats were determined by using the indirect tail-cuff method. RESULTS: Bdph (30 mg/kg, i.p.) did not affect baseline systolic pressure in conscious normotensive and spontaneous hypertensive rats. Bdph (30 mg/kg, i.p.) also did not affect log dose-response curves of prazosin, clonidine and Bay K 8644, a Ca(2+) channel activator, in normotensive rats. However, Bdph (30 mg/kg, i.p.) similar to 4-aminopyridine (4-AP, 0.4 mg/kg, i.p.), a K(+) channel blocker, non-parallelly but surmountably, and partially similar to glibenclamide (GBC, 10 mg/kg, i.v.), an ATP-sensitive K(+) channel blocker, surmountably but not parallelly rightward shifted the log dose-systolic pressure reduction curve of cromakalim, an ATP-sensitive K(+) channel opener, in normotensive rats, respectively. DISCUSSION: The antagonistic effect of Bdph against cromakalim was similar to that of 4-AP, a K+ channel blocker of Kv1 family, and partially similar to that of GBC, an ATP-sensitive K+ channel blocker. Thus, Bdph may be a kind of K+ channel blockers, which have been reviewed to have a potential clinical use for Alzheimer disease. Indeed, Bdph has also been reported to reverse the deficits of inhibitory avoidance performance and improve memory in rats. Recently, 4-AP was reported to treat Episodic ataxia type 2 (EA2) which is a form of hereditary neurological disorder. Consistently, Bdph was recently reported to have antihyperglycemic activity in mice, since GBC is a powerful oral hypoglycemic drug. CONCLUSIONS: Bdph similar to 4-AP and partially similar to GBC may block Kv1 family and ATP-sensitive K(+) channels in conscious normotensive rats.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Anidridos Ftálicos/administração & dosagem , Animais , Cromakalim/efeitos adversos , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipoglicemiantes/química , Masculino , Estrutura Molecular , Anidridos Ftálicos/química , Canais de Potássio/genética , Canais de Potássio/metabolismo , Ratos , Ratos Endogâmicos SHR
10.
Eur J Pharmacol ; 767: 135-43, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26463037

RESUMO

Airway inflammation plays a major role in the pathophysiology of lung inflammatory diseases such as asthma. Thrombin, a serine protease, is known to mediate central functions in thrombosis and hemostasis and also plays a critical role in lung inflammation via producing chemokine release including interleukin (IL)-8/CXCL8. Our previous studies showed that c-Src- and Rac-dependent nuclear factor (NF)-κB signaling pathways participate in thrombin-induced IL-8/CXCL8 release in human lung epithelial cells. In this study, we further investigated the role of casein kinase 2 (CK2)/mitogen stress-activated protein kinase 1 (MSK1)-dependent p65 phosphorylation in thrombin-induced NF-κB activation and IL-8/CXCL8 release. Thrombin-induced IL-8/CXCL8 release was inhibited by CK2 inhibitors (apigenin and tetrabromobenzotriazole, TBB), small interfering RNA of CK2ß (CK2ß siRNA), and MSK1 siRNA. Treatment of cells with thrombin caused increases in CK2ß phosphorylation at Ser209, which was inhibited by a protein kinase C α (PKCα) inhibitor (Ro-32-0432). Thrombin-induced MSK1 phosphorylation at Ser581 and Akt phosphorylation at Ser473 were inhibited by apigenin. Moreover, the thrombin-induced increase in IL-8/CXCL8 release was attenuated by p65 siRNA. Stimulation of cells with thrombin resulted in an increase in p65 phosphorylation at Ser276, which was inhibited by apigenin and MSK1 siRNA. Thrombin-induced κB-luciferase activity was also inhibited by apigenin and MSK1 siRNA. Taken together, these results show that thrombin activates the PKCα/CK2/MSK1 signaling pathways, which in turn initiates p65 phosphorylation and NF-κB activation, and ultimately induces IL-8/CXCL8 release in human lung epithelial cells.


Assuntos
Caseína Quinase II/metabolismo , Células Epiteliais/metabolismo , Interleucina-8/metabolismo , NF-kappa B/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Trombina/farmacologia , Animais , Apigenina/farmacologia , Caseína Quinase II/antagonistas & inibidores , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Humanos , Indóis/farmacologia , Pulmão/metabolismo , Fosforilação/efeitos dos fármacos , Pirróis/farmacologia , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/efeitos dos fármacos , Trombina/antagonistas & inibidores , Fator de Transcrição RelA/metabolismo , Triazóis/farmacologia
11.
J Chin Med Assoc ; 77(7): 367-73, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24908182

RESUMO

BACKGROUND: Phagocytic clearance of apoptotic neutrophils by tissue macrophages is a crucial component in the resolution phase of acute inflammation. However, the number of tissue macrophages is low and not likely to cope satisfactorily with the excess number of dying neutrophils. Although recent studies have reported that neutrophils are able to engulf apoptotic neutrophils, the mechanisms by which living neutrophils are attracted to apoptotic neutrophils are poorly defined. Increased amounts of CX3CL1 and microparticles (MPs) are rapidly released by apoptotic cells, and are involved in the chemoattraction of mononuclear phagocytes toward apoptotic cells. The current study investigated the role of CX3CL1 in the chemoattraction of all-trans retinoic acid (ATRA)-treated NB4 (ATRA-NB4) cells toward apoptotic cells. METHODS: Conditioning medium and MPs were harvested from apoptotic ATRA-NB4 cell cultures to determine their effects on living ATRA-NB4 cells by transmigration assay and adhesion assay. The cytokine levels in the conditioning medium were determined by enzyme-linked immunosorbent assay. Expression of CX3CR1 (a receptor of CX3CL1) on ATRA-NB4 cells was determined by flow cytometric analysis. RESULTS: ATRA-NB4 cells transmigrated toward the apoptotic ATRA-NB4 cells, and this chemoattraction was partially inhibited when the CX3CR1 on ATRA-NB4 cells was blocked by its specific antibody. Both exogenous CX3CL1 and MPs released by apoptotic ATRA-NB4 cells were able to enhance the chemoattraction of ATRA-NB4 cells toward apoptotic cells or the adhesion of ATRA-NB4 cells to endothelial cells. CX3CL1 was expressed on the surface of MPs, and blocking this CX3CL1 with its specific antibody was able to partially inhibit the chemoattractive property of MPs. CONCLUSION: CX3CL1, in either the free or MP form, is released rapidly by apoptotic ATRA-NB4 cells after induction of apoptosis to mediate the chemoattraction of living ATRA-NB4 cells toward apoptotic cells.


Assuntos
Apoptose , Quimiocina CX3CL1/fisiologia , Quimiotaxia/fisiologia , Leucemia Promielocítica Aguda/patologia , Neutrófilos/fisiologia , Tretinoína/farmacologia , Células Cultivadas , Citometria de Fluxo
12.
Chin J Physiol ; 57(3): 152-7, 2014 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-24826783

RESUMO

Mechanical ventilation using endotracheal tube (ETT) intubation is crucial in saving life but may also cause ventilator-associated pneumonia resulting in morbidity and mortality. The purpose of this study was to examine the effects of intubation duration on pathogen colonization rates of ETT cuff region, and its association with the subsequent re-intubation and tracheostomy. We enrolled 92 patients who were successfully weaned from ventilator and were extubated within 20 days of intubation duration. Patients were divided into Group I and II based on intubation for 1-9 days and 10-20 days, respectively. Pathogen colonization over ETT cuff region and extra-cuff region (including sputum and ETT aspirates) were assessed. As compared to Group I patients, Group II patients had a significant higher pathogen colonization rate (100% vs. 69.2%; P < 0.001) in the ETT cuff samples, but not in the extra-cuff samples (92.6% vs. 84.8%; P = 0.442). Further studies demonstrated that there was no difference between Group I and II patients in the percentages of patients with the same pathogen over both the cuff and extra-cuff samples (35.5% vs. 30.8%; P = 0.925), suggesting that the increased pathogen colonization rate over the ETT cuff region was least likely from the extra-cuff region. In addition, the results showed that longer intubation was also associated with increased tracheostomy rate from 9.3% to 28.9% for Group I and Group II respectively (P = 0.025). We conclude that longer intubation has a higher pathogen colonization rate over the ETT cuff region in patients receiving mechanical ventilation support; longer intubation also increases the trend of receiving re-intubation and tracheostomy. Our findings indicate that it is crucial to remove ETT as soon as possible and perform pathogen culture over the ETT cuff regions immediately after extubation.


Assuntos
Contaminação de Equipamentos/estatística & dados numéricos , Controle de Infecções , Intubação Intratraqueal/efeitos adversos , Respiração Artificial/efeitos adversos , Traqueostomia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Infecções por Serratia/epidemiologia , Serratia marcescens/isolamento & purificação , Stenotrophomonas maltophilia/isolamento & purificação
13.
Cell Physiol Biochem ; 33(3): 594-604, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24603149

RESUMO

BACKGROUND/AIMS: During the resolution phase of inflammation, release of "find-me" signals by apoptotic cells is crucial in the chemoattraction of macrophages toward apoptotic cells for subsequent phagocytosis, in which microparticles derived from apoptotic cells (apo-MPs) are involved. A recent study reports that CX3CL1 is released from apoptotic cells to stimulate macrophages chemotaxis. In this study, we investigated the role of CX3CL1 in the apo-MPs in the cell-cell interaction between alveolar macrophage NR8383 cells and apoptotic all-trans retinoic acid-treated NB4 (ATRA-NB4) cells. METHODS/RESULTS: Apoptotic ATRA-NB4 cells and their conditioning medium (CM) enhanced the chemoattraction of NR8383 cells as well as their phagocytosis activity in engulfing apoptotic ATRA-NB4 cells. The levels of CX3CL1(+) apo-MPs and CX3CL1 were rapidly elevated in the CM of ATRA-NB4 cell culture after induction of apoptosis. Both exogenous CX3CL1 and apo-MPs enhanced the transmigration of NR8383 cells toward apoptotic ATRA-NB4 cells. This pro-transmigratory activity was able to be partially inhibited either by blocking the CX3CR1 (CX3CL1 receptor) of NR8383 cells with its specific antibody or by blocking the surface CX3CL1 of apo-MPs with its specific antibody before incubating these apo-MPs with NR8383 cells. CONCLUSION: CX3CL1(+) apo-MPs released by apoptotic cells mediate the chemotactic transmigration of alveolar macrophages.


Assuntos
Apoptose , Micropartículas Derivadas de Células/metabolismo , Quimiocina CX3CL1/metabolismo , Quimiotaxia , Leucemia Promielocítica Aguda/metabolismo , Macrófagos Alveolares/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Linhagem Celular Tumoral , Micropartículas Derivadas de Células/patologia , Humanos , Leucemia Promielocítica Aguda/patologia , Macrófagos Alveolares/patologia , Ratos , Ratos Sprague-Dawley , Tretinoína/farmacologia
14.
Chin J Physiol ; 57(1): 1-7, 2014 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-24621333

RESUMO

Annexin A1 (AnxA1), originally identified as a glucocorticoid-regulated protein, is an impor- tant endogenous anti-inflammatory mediator during the resolution phase of inflammation, and its cir- culating level has been rarely studied in sepsis patients. Glucocorticoid has been extensively used in treating patients with sepsis. However, it is unclear whether endogenous cortisol or exogenous glucocor- ticoid contributes to the regulation of AnxA1 levels in peripheral blood of sepsis patients. The aim of this study was to investigate: [1] serial changes over time in the plasma levels of AnxA1 and cortisol in sepsis patients; and [2] prognostic value of AnxA1 level in the survival of sepsis patients. Fifty-eight adult sepsis patients admitted to an intensive care unit (ICU) were enrolled. The plasma levels of cortisol and AnxA1 were determined by specific enzyme-link immunosorbent assay. Results show that the median daily levels of cortisol at the 1st, 3rd, 5th and 7th day after admission to ICU were signifi- cantly elevated over the cortisol level of the control subjects. However, the AnxA1 level was elevated in only thirty-three patients (56%) over the observation period. There was no significant correlation between cortisol levels and AnxA1 levels. Further analysis indicated that steroid treatment resulted in significant elevation of the cortisol level over time, but did not affect the AnxA1 level. AnxA1 levels were also not statistically different between surviving and non-surviving patients. In conclusions, the circu- lating level of AnxA1 is elevated in a subgroup of sepsis patients, and the AnxA1 level does not correlate with the cortisol level in the peripheral blood of sepsis patients.


Assuntos
Anexina A1/sangue , Hidrocortisona/sangue , Sepse/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sepse/mortalidade
15.
Talanta ; 120: 386-90, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24468386

RESUMO

The Hadamard transform-gas chromatography/mass spectrometry (HT-GC/MS) technique was successfully employed to detect acetone, a biomarker for diabetes mellitus (DM) prediction, in human breath. Samples of exhaled breath were collected from four DM patients (one type-I and three type-II) and eight volunteers (nondiabetic healthy subjects), respectively. The gas samples, without any pretreatment, were simultaneously injected into a GC column through a Hadamard-injector based on Hadamard codes. Under optimized conditions, when cyclic S-matrix orders of 255, 1023 and 2047 were used, the S/N ratios of the acetone signals were substantially improved by 8.0-, 16.0- and 22.6-fold, respectively; these improvements are in good agreement with theoretically calculated values. We found that the breath acetone concentration levels in the four DM patients and the eight volunteers ranged from 1 to 10 ppmv and 0.1 to 1 ppmv, respectively.


Assuntos
Acetona/análise , Testes Respiratórios/instrumentação , Diabetes Mellitus/diagnóstico , Cromatografia Gasosa-Espectrometria de Massas/instrumentação , Acetona/metabolismo , Diabetes Mellitus/metabolismo , Desenho de Equipamento , Expiração , Humanos , Prognóstico
17.
IEEE Trans Biomed Circuits Syst ; 8(6): 765-78, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25576573

RESUMO

Ventilator-associated pneumonia (VAP) still lacks a rapid diagnostic strategy. This study proposes installing a nose-on-a-chip at the proximal end of an expiratory circuit of a ventilator to monitor and to detect metabolite of pneumonia in the early stage. The nose-on-a-chip was designed and fabricated in a 90-nm 1P9M CMOS technology in order to downsize the gas detection system. The chip has eight on-chip sensors, an adaptive interface, a successive approximation analog-to-digital converter (SAR ADC), a learning kernel of continuous restricted Boltzmann machine (CRBM), and a RISC-core with low-voltage SRAM. The functionality of VAP identification was verified using clinical data. In total, 76 samples infected with pneumonia (19 Klebsiella, 25 Pseudomonas aeruginosa, 16 Staphylococcus aureus, and 16 Candida) and 41 uninfected samples were collected as the experimental group and the control group, respectively. The results revealed a very high VAP identification rate at 94.06% for identifying healthy and infected patients. A 100% accuracy to identify the microorganisms of Klebsiella, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida from VAP infected patients was achieved. This chip only consumes 1.27 mW at a 0.5 V supply voltage. This work provides a promising solution for the long-term unresolved rapid VAP diagnostic problem.


Assuntos
Candidíase/diagnóstico , Nariz Eletrônico , Pneumonia Bacteriana/diagnóstico , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Testes Respiratórios/instrumentação , Testes Respiratórios/métodos , Candidíase/metabolismo , Humanos , Pneumonia Bacteriana/metabolismo , Pneumonia Associada à Ventilação Mecânica/metabolismo
18.
J Chin Med Assoc ; 76(9): 486-90, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23769883

RESUMO

BACKGROUND: The relationship between the various cytokine responses that occur during sepsis remains controversial. Emerging evidence indicates that the proinflammatory and anti-inflammatory responses are regulated simultaneously from the beginning of sepsis. However, the roles of the novel anti-inflammatory mediators annexin (Anx)A1 and lipoxin (LX)A4 and the proinflammatory cytokines neutrophil gelatinase-associated lipocalin (NGAL) and macrophage inflammatory protein (MIP)-3a have been studied. METHODS: In this study, the plasma levels of AnxA1, LXA4, NGAL, MIP-3a, interleukin (IL)-8 and IL-6 in patients with sepsis were determined on admission to the intensive care unit. The patients were classified into survivors and non-survivors based on their outcome on day 28. RESULTS: AnxA1 and LXA4 levels were decreased in sepsis patients compared with control patients, whereas the levels of the proinflammatory cytokines MIP-3a, NGAL, IL-8, and IL-6 were elevated. Furthermore, a significantly higher level of MIP-3a was detected in nonsurviving patients compared with surviving patients (p < 0.05), whereas there were no significant differences between these two groups for the levels of the other mediators. Correlation analysis demonstrated that only NGAL level was closely correlated with the level of IL-6. Univariate analysis indicated that the levels of MIP-3a and IL-8 were independent factors associated with patient survival, but this was not confirmed by the multivariate analysis. CONCLUSION: AnxA1 and LXA4 plasma levels were found to be decreased in sepsis patients, whereas the levels of MIP-3a and NGAL were found to be elevated. This warrants further study in order to determine the clinical implications of these changes.


Assuntos
Quimiocina CCL20/sangue , Lipocalinas/sangue , Lipoxinas/sangue , Proteínas Proto-Oncogênicas/sangue , Sepse/sangue , Proteínas de Fase Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Anexina A1/sangue , Feminino , Humanos , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , Sepse/mortalidade
19.
J Cell Biochem ; 114(3): 551-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22991072

RESUMO

Annexin A1 (AnxA1) is an important anti-inflammatory mediator during granulocytic differentiation in all trans-retinoic acid (ATRA) treated acute promyelocytic leukemic (APL) cells. Dexamethasone has been used successfully to prevent complications in ATRA-treated APL patients, although its mechanism of action is still not clear. In the present study, we have examined the effect of dexamethasone on the modulation of AnxA1 in ATRA-APL NB4 (ATRA-NB4) cells, ATRA-NB4 cells-derived microparticles (MPs) and its role during cell-cell interaction between ATRA-NB4 cells and endothelial cells. Our results have shown that dexamethasone can inhibit the percentage of ATRA-NB4 cells expressing surface AnxA1 and its receptor FPR2/ALX in a time-dependent manner based on flow cytometric analysis. However, dexamethasone treatment of ATRA-NB4 cells has no significant effect on the level of AnxA1 mRNA, the total cellular level of AnxA1 protein or the release of AnxA1 from these cells, as determined by RT-PCR, Western blotting, and ELISA, respectively. Further studies demonstrate that dexamethasone is able to significantly inhibit the adhesion of ATRA-NB4 cells to endothelial cells, and this anti-adhesive effect can be inhibited if the cells were pre-treated with a neutralizing antibody specific for AnxA1. Finally, dexamethasone also enhances the release of AnxA1-containing MPs from ATRA-NB4 cells which can in turn prevent the adhesion of the ATRA-NB4 cells to endothelial cells. We conclude that biologically active AnxA1 originating from dexamethasone-treated ATRA-APL cells and their MPs plays an anti-adhesive effect and this contributes to inhibit the adhesion of ATRA-APL cell to endothelial cells.


Assuntos
Anexina A1/metabolismo , Adesão Celular/efeitos dos fármacos , Dexametasona/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Leucemia Promielocítica Aguda/metabolismo , Anexina A1/biossíntese , Anexina A1/genética , Anticorpos Neutralizantes/imunologia , Diferenciação Celular , Linhagem Celular Tumoral , Micropartículas Derivadas de Células , Humanos , Mediadores da Inflamação , RNA Mensageiro/biossíntese , Tretinoína/farmacologia
20.
Chin J Physiol ; 55(3): 178-83, 2012 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-22784282

RESUMO

"We undertook this study to investigate the adequate oxygen concentration that can be applied safely to the treatment of pneumothorax. Complete unilateral pneumothorax was induced artificially in rabbits, which were subsequently treated with various inspired oxygen fractions (FIO2; 21%, 60%, 80% or 100%). The pneumothorax resolution time was measured together with the levels of IL-1ß and IL-8 in broncho-alveolar lavage (BAL) and plasma samples. Furthermore, the lungs from these animals were examined for histolopathological evidence of oxygen toxicity. The results showed that the resolution time was significantly faster in the pneumothorax rabbits when treated with higher FIO2. Significantly higher levels of IL-1 ß were detected in BAL samples collected from the pneumothorax-rabbits that had received FIO2 at levels of either 80% or 100% (P < 0.05), but not in those with FIO2 at the 60% level. However, there was no significant change in the level of IL-8 in the BAL when the pneumothorax-rabbits were treated with different FIO2 levels. In addition, no evidence of oxygen toxicity was found when the lung tissues were examined. The data indicated that higher FIO2 treatment can accelerate the resolution of pneumothorax, but caution should be exercised with regard to associated oxygen toxicity when the FIO2 used is greater than 80%. We conclude that treatment with 60% FIO2 is an appropriate concentration for oxygen therapy for the treatment of pneumothorax in this model."


Assuntos
Oxigênio , Pneumotórax , Animais , Interleucina-1beta , Interleucina-8 , Pulmão , Oxigênio/sangue , Coelhos
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