Cysteinyl leukotrienes and collagen type I synthesis in asthma.
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Acetates↗
Biomedical subjects
Tohru Sakamoto
Publications and source records attributed to Tohru Sakamoto.
Polymorphisms of IL4, IL13, and ADRB2 genes in COPD.
STUDY OBJECTIVES: Interleukin (IL)-4, IL-13, and beta(2)-adrenoceptor (ADRB2) are involved in airway hyperresponsiveness (AHR), and their coding genes are located on chromosome 5q31-q33. AHR is one of the risk factors for COPD. Investigating polymorphisms within these genes may help to pinpoint the genetic susceptibility to COPD. SUBJECTS AND MEASUREMENTS: A case-control association study was conducted on two different ethnic groups: Japanese subjects (88 patients with COPD and 61 control subjects) and Egyptian subjects (106 patients with COPD and 72 control subjects). The following polymorphisms were genotyped: - 589 C/T, - 33 C/T, and variable number of tandem repeat (VNTR) in IL4, - 1111 C/T and + 2044 G/A in IL13, and + 46 A/G and + 79 C/G in ADRB2. Pairwise haplotype frequencies as well as genotype and allele frequencies were analyzed. RESULTS: The distribution of the genotype frequencies of ADRB2 + 79 C/G was significantly different between the COPD and the control groups in the Egyptians (p = 0.002). The distributions of the haplotypes in the Japanese (IL4 - 589 C/T: IL4 VNTR; IL4 - 33 C/T: IL4 VNTR) [corrected p values < 0.001 and 0.022, respectively], and those in the Egyptians (IL4 - 589 C/T: ADRB2 + 79 C/G; IL4 VNTR: ADRB2 + 79 C/G) [corrected p values, 0.033 and 0.001, respectively] showed significant differences between the COPD and the control groups. CONCLUSIONS: The ADRB2 + 79 C/G polymorphism and the haplotypes shown in this study may be involved in the pathogenesis of COPD.
Aged↗
Significance of serum atrial and brain natriuretic peptide release after coronary artery bypass grafting.
PURPOSE: The aim of this study was to examine whether serial changes in endogenous levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were associated with clinical status after coronary artery bypass grafting (CABG). METHODS: Serial blood samples were collected from 14 patients preoperatively, 2, 5 and 8 h after cardiopulmonary bypass, then up to 7 days postoperatively. Follow-up was done 2 years later. RESULTS: We found a significant increase from the preoperative values in ANP and BNP concentrations on postoperative days 1 and 3 (P < 0.001). The elevated BNP concentration correlated with the preoperative values (r2 = 0.824, P = 0.0005). Retrospectively, the BNP concentrations after surgery in the patients who suffered cardiac events within 2 years were significantly higher than those in the patients free of cardiac events (P = 0.0023). CONCLUSION: The BNP concentration after CABG was found to be corrected with interim clinical status after surgery. Thus, it may be necessary for patients with a high postoperative BNP concentration to be closely monitored for coronary events.
Atrial Natriuretic Factor↗
Anti-inflammatory activity of creatine supplementation in endothelial cells in vitro.
1 Creatine (CR) supplementation augments muscle strength in skeletal muscle cells by increasing intracellular energy pools. However, the effect of CR supplementation on endothelial cells remains to be clarified. 2 In this study, we investigated whether CR supplementation had any anti-inflammatory activity against human pulmonary endothelial cells in culture. 3 We confirmed that supplementation with 0.5 mM CR significantly increased both intracellular CR and phosphocreatine (PC) through a CR transporter while keeping intracellular ATP levels constant independent of CR supplementation and a CR transporter antagonist. 4 In the assay system of endothelial permeability, supplementation with 5 mM CR significantly suppressed the endothelial permeability induced by serotonin and H(2)O(2). 5 In cell adhesion experiments, supplementation with 5 mM CR significantly suppressed neutrophil adhesion to endothelial cells. 6 In the measurement of adhesion molecules, CR supplementation with more than 0.5 mM CR significantly inhibited the expressions of ICAM-1 and E-selectin on endothelial cells, and the inhibition was significantly suppressed by an adenosine A(2A) receptor antagonist. 7 The present study suggests that CR supplementation has anti-inflammatory activities against endothelial cells.
Adenosine Triphosphate↗
Sputum E-cadherin and asthma severity.
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Asthma↗
S-carboxymethylcysteine inhibits neutrophil activation mediated by N-formyl-methionyl-leucyl-phenylalanine.
In this study, the possible mechanisms of action for the inhibitory effects of S-carboxymethylcysteine on the activation of human neutrophils by N-formyl-methionyl-leucyl-phenylalanine (FMLP) were investigated. Preincubation of neutrophils with more than 10 microg/ml of S-carboxymethylcysteine was found to impair neutrophil chemotactic activity toward FMLP, and to inhibit FMLP-mediated neutrophil adherence to pulmonary vascular endothelial cells. Preincubation of neutrophils with 10 and 100 microg/ml of S-carboxymethylcysteine decreased in the production of inositol 1,4,5-triphosphate (IP(3)) and diacylglycerol in neutrophils stimulated with FMLP, respectively. Preincubation of neutrophils with S-carboxymethylcysteine did not affect the cellular cyclic AMP (cAMP) levels in neutrophils stimulated with FMLP. S-carboxymethylcysteine inhibited the enzymatic activity of phosphatidyl inositol-specific phospholipase C in vitro in a concentration-dependent manner. These findings indicate that S-carboxymethylcysteine attenuates FMLP-stimulated neutrophil activation at least in part by inhibiting phosphatidyl inositol-specific phospholipase C-mediated signal transduction.
Carbocysteine↗
Ebselen suppresses late airway responses and airway inflammation in guinea pigs.
Although ebselen, a seleno-organic compound, inhibits inflammation in various animal models, its efficacy as an anti-asthma drug remains to be clarified. In this study, we investigated the inhibitory effect of ebselen on a guinea pig asthma model. Ebselen was orally administered at dosages of 1-20 mg/kg 2 h before an ovalbumin (OA) challenge, and then airway responses, airway inflammation, the generation of superoxide, H(2)O(2), and nitrotyrosine, and the induction of inducible nitric oxide synthase (iNOS) were evaluated. Sensitized animals challenged with OA aerosol showed dual airflow limitations, i.e., immediate and late airway responses (IAR and LAR). Ebselen significantly inhibited LAR at dosages greater than 10 mg/kg, but did not inhibit IAR at any dosage. Bronchoalveolar lavage (BAL) examination showed that airway inflammation was significantly suppressed by ebselen at 10 mg/kg. The generation of superoxide and H(2)O(2) occurred on endothelial cells of LAR bronchi, and was inhibited by 10 mg/kg of ebselen. Superoxide generation was inhibited by diphenyleneiodonium chloride (DPI), a NAD(P)H oxidase inhibitor, but not by allopurinol, a xanthine oxidase inhibitor. Immunoreactivities for iNOS and nitrotyrosine were also observed on endothelial cells of LAR bronchi and were abolished in ebselen-treated animals. The present findings suggest that ebselen can be applied as a new therapeutic agent for asthma. The possible mechanisms by which ebselen inhibits LAR likely involve suppression of oxidant formation and iNOS induction in endothelial cells.
Airway Resistance↗
Non-depolarizing cardioplegia activates Ca2+-ATPase in sarcoplasmic reticulum after reperfusion.
OBJECTIVES: Depolarizing cardioplegia is the most common method for myocardial preservation in cardiac operations. However, depolarizing cardioplegia causes depolarization of the membrane potential by extracellular hyperkalemia, resulting in depletion of energy stores and calcium overload. This study examined the hypothesis that non-depolarizing cardioplegia would provide superior protection compared with depolarizing cardioplegia. METHODS: In an isolated rat heart Langendorff model, hearts were perfused for 10 min with St. Thomas' Hospital cardioplegic solution (Group I: n=20), St. Thomas' Hospital cardioplegic solution+Lidocaine 1 mM (Group II: n=20) or non-depolarizing cardioplegia (Group III: n=20). The hearts then were subjected to 60 min of normothermic global ischemia, after which they were perfused with Krebs-Henseleit buffer at 37 degrees C for 30 min. The percent recovery of functional data, myocardial cyclic AMP contents, and myocardial cyclic GMP contents were recorded at each time point (base, after the administration of cardioplegia, after global ischemia, and after 30 min of reperfusion). Ca(2+)-ATPase in sarcoplasmic reticulum was measured at pre-ischemia and 30 min of reperfusion. RESULTS: The percent recovery of developed pressure and +/-dp/dt were significantly higher in Group III than in other groups. Myocardial cyclic AMP and GMP contents were elevated after reperfusion in all groups. However, in Group III, myocardial cyclic AMP contents after 30 min of reperfusion were significantly higher than in other groups (Group III: 14.7+/-1.6 vs. Group I: 8.7+/-1.0, Group II: 8.3+/-0.2 pmol/mg dry weight, P=0.05) but not cGMP. The sarcoplasmic reticulum Ca(2+)-ATPase activities at 30 min of reperfusion significantly increased in Group III compared with Groups II and I (Group III: 70.3+/-3.6 vs. Group I: 46.8+/-3.4, Group II: 53.9+/-6.1 micromol Pi/mg per h, P=0.025 and P=0.030). CONCLUSIONS: Non-depolarizing cardioplegia induced the activity of Ca(2+)-ATPase in sarcoplasmic reticulum after reperfusion. The activity would be increased by the cyclic AMP pathway. These findings suggested that non-depolarizing cardioplegia prevented calcium overload after reperfusion, especially decreased cytosolic calcium during the diastolic phase.
Animals↗
Involvement of thromboxane A(2) in airway mucous cells in asthma-related cough.
The aim of this study was to elucidate the role of thromboxane A(2) (TxA(2)) on asthma-related cough in guinea pigs. Animals were immunosensitized and repeatedly challenged with ovalbumin as an antigen. Coughs were induced by the inhalation of 10(-5) M capsaicin solution for 10 min. Thromboxane synthetase (TxS) inhibitor OKY-046 and thromboxane-receptor antagonist AA-2414 significantly inhibited cough responses in repeatedly challenged animals. Inhalation of TxA(2) mimic STA-2- potentiated cough responses in normal and immunosensitized animals but not in repeatedly challenged ones. Moreover, STA-2-potentiated coughs were inhibited by administration of neurokinin-receptor antagonist FK-224. In repeatedly challenged animals, concentration of TxB(2) in airway lavage fluid, expression of TxS mRNA in tracheal epithelia, and the immunostaining intensity against TxS in mucous cells of the epithelium significantly increased compared with normal and sensitized animals. These results suggest that TxA(2) derived from mucous cells potentiated cough responses to capsaicin in allergic airway inflammation.
Animals↗
Differential regulation of MMP-2, TIMP-2 and IL-6 in valve replacement versus CABG patients.
BACKGROUND: Extracellular matrix degradation may play an important role in left ventricular (LV) remodeling. It has been reported that matrix metalloproteinase-2 (MMP-2) is activated under mechanical stress conditions. Therefore, we examined the release of MMP-2, its inhibitor and interleukin-6 (IL-6), which affects MMPs, in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Arterial blood samples were obtained from 20 patients undergoing cardiac surgery and six patients with descending aortic replacement (as noncardiac control) with CPB. Samples were assayed for plasma MMP-2, tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) and IL-6 concentration. RESULTS: Plasma MMP-2 concentrations in the valvular disease patients were greater than in other patients (p < 0.05) and correlated with the LV mass (r=0.810, p < 0.0001) prior to the operation. Plasma MMP-2 concentrations decreased during CPB and gradually recovered to the baseline levels after CPB. Plasma TIMP-2 concentrations increased significantly during and after CPB in a biphasic manner. Plasma IL-6 concentrations also increased significantly during CPB (p < 0.05 versus baseline levels). CONCLUSION: Plasma MMP-2 concentrations reflect the state of the left ventricle, and changes in plasma MMP-2 and TIMP-2 concentrations during CPB may play an important role in LV remodeling after cardiac surgery.
Cardiopulmonary Bypass↗
Evaluation of native left ventricular function during mechanical circulatory support: theoretical basis and clinical limitations.
Left ventricular function on patients with heart disease is now evaluated by echocardiography, but these dimensional changes are erroneous in the patient supported by left ventricular assist device because of mechanical unloading for the failing heart. Left ventricular end-systolic pressure-volume relationship provides theoretically most reliable left ventricular contractility. Recently, some patients have weaned from the device because of unexpected recovery of myocardial contractility. But it is very important to evaluate the left ventricular function just before the weaning, and to predict the longevity of the recovered function to keep the good quality of life. Current clinical situation in the patients with ventricular assist device, and theoretical limitations to evaluate the recovering myocardium are discussed.
Heart Failure↗
One piece ultracompact totally implantable electromechanical total artificial heart for permanent use.
An ultracompact, one piece, totally implantable electromechanical total artificial heart (TAH) has been developed as a permanent replacement for failing hearts. It consists of left and right pusher plate blood pumps (stroke volume 55 ml) made of titanium alloy (Ti-6Al-7Nb) sandwiching a miniaturized electromechanical actuator between them. The diameter of the TAH is 90 mm, with a thickness of 70 mm, yielding an overall volume of 400 ml. It weighs 450 g. Although it is miniaturized, it provided a maximum pump output of 8 L/min against a left afterload of 100 mm Hg. It required approximately 12 watts to provide a pump output of 6.5 L/min with maximum efficiency of 13.5%. To balance left and right flow, the right stroke length was made 10% shorter than the left, and an auxiliary compliance chamber was used to compensate for additional flow differences between them. Motor commutation pulses and a Hall effect pusher plate sensor signal were used in the controller to implement the left master alternate variable rate mode. The calf fitting study revealed excellent anatomic compatibility, and the first successful survivor was obtained in December 2001. Studies of system endurance and biocompatibility are required to ensure long-term reliability. This TAH is promising for permanent replacement of the failing heart as well as for bridge to heart transplantation for the smaller size group of end-stage cardiac patients.
Animals↗