PubMed Health⌕ Search

Biomedical subjects

M Shiga

Publications and source records attributed to M Shiga.

At least 19 recordsLinked to original sources
PubMed2003

Effects of ropivacaine on human neutrophil function: comparison with bupivacaine and lidocaine.

BACKGROUND AND OBJECTIVE: Neutrophils are important both for the immunological defence system and for the inflammatory tissue autoinjury mechanism. However, many local anaesthetics impair certain neutrophil functions. The aim was to assess the effects of ropivacaine, bupivacaine and lidocaine on human neutrophils from adult volunteers. METHODS: Chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion ([Ca2+]i) concentrations and protein kinase C activity were measured in the absence and presence of ropivacaine, bupivacaine or lidocaine. The lowest concentrations of the local anaesthetics were similar to those clinically observed in the plasma. RESULTS: Bupivacaine did not affect any neutrophil function (P > 0.05). Ropivacaine failed to change chemotaxis or phagocytosis, while lidocaine suppressed both these neutrophil functions. Ropivacaine (15, 150 microg mL(-1)) and lidocaine (20, 200 microg mL(-1)) impaired neutrophil production of O2-, H2O2 and OH- (P < 0.05) at similar rates (by 7-10%). These same concentrations of ropivacaine and lidocaine suppressed [Ca2+1i elevation. Finally, neither ropivacaine nor bupivacaine inhibited protein kinase C activity, while lidocaine did. CONCLUSIONS: Suppression of the [Ca2+]i response in neutrophils by ropivacaine may represent one of the mechanisms responsible for the impairment of neutrophil functions. It should be emphasized that the inhibitory effects of ropivacaine are minor and are attained only at high concentrations, which may minimize the clinical implication of ropivacaine-associated impairment of reactive oxygen species production. Further studies using in vivo systems are required to identify the inhibitory effects of ropivacaine on reactive oxygen species production in clinical settings.

Adult↗
PubMed2001

Effect of methylprednisolone on phospholipase A(2) activity and lung surfactant degradation in acute lung injury in rabbits.

Glucocorticoids are the most potent and widely used anti-inflammatory agents, but they are not particularly effective against early phase of acute respiratory distress syndrome. We investigated whether methylprednisolone, a synthetic glucocorticoid, could inhibit increase of phospholipase A(2) activity in the lung and lead to protection against a model of acute respiratory distress syndrome in rabbits. Infusion of oleic acid (0.1 ml/kg/h, i.v. for 2 h) provoked pulmonary hemorrhage and edema, protein leakage and massive neutrophil infiltration, resulted in severe hypoxemia and impaired lung compliance, accompanying the increase of phospholipase A(2) activity and interleukin-8, and degradation of surfactant in the bronchoalveolar lavage fluid. Infusion of methylprednisolone (60 mg/kg/h, i.v. for 30 min before the oleic acid and then 0.5 mg/kg/h, i.v. for 6 h) did not improve the above described lung injury induced by oleic acid, nor did it suppress phospholipase A(2) activity and degradation of surfactant in bronchoalveolar lavage fluid, while it strongly reduced interleukin-8 levels in both plasma and bronchoalveolar lavage fluid. We conclude that methylprednisolone did not attenuate oleic acid-induced acute lung injury and this can be explained partly by its failure to reduce the increase of phospholipase A(2) activity and the surfactant degradation in the lung, which might also account for its clinical ineffectiveness against early acute respiratory distress syndrome.

Animals↗
PubMed2001

Evaluation of atomic integrals for hybrid Gaussian type and plane-wave basis functions via the McMurchie-Davidson recursion formula.

A convenient formalism is developed for the evaluation of atomic integrals composed of a hybrid Gaussian type function and plane-wave (GTF-PW) basis set, based upon the recursion scheme proposed by McMurchie and Davidson [L. E. McMurchie and E. R. Davidson, J. Comput. Phys. 26, 218 (1978)] which was originally for Gaussian type basis functions. We show that revisions of recursion relations in the original article are necessary in order to allow systematic production of overlap, kinetic energy, nuclear attraction, and electron repulsion integrals in compact forms. Involving easy calculation of complex incomplete gamma functions, the recursion relations enable the use of hybrid GTF-PW basis functions with arbitrarily large angular momentum. This basis function can be applied to the first-principle calculation for solids involving localized electron orbitals.

Journal Article↗
PubMed2001

Epidemiological studies of tobacco smoking and dependence in Japan.

In this study, we attempted to determine the prevalence of tobacco or nicotine dependence in current smokers in Japan and to assess the relationship between alcoholism and tobacco or nicotine dependence. The subjects consisted of 246 alcohol-dependent and 1,111 non-alcohol-dependent individuals. We used a questionnaire, consisting of items obtained from the World Health Organization's The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines (ICD-10) and the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for tobacco or nicotine dependence. The prevalence of tobacco dependence diagnosed according to the ICD-10 criteria was 23.9% among all subjects. The prevalence of tobacco dependence diagnosed according to the ICD-10 criteria was higher in alcohol-dependent individuals (58.1%) than in nondrinkers or social drinkers (12.8%). Alcohol-dependent subjects consumed significantly more nicotine per day than did nondrinkers or social drinkers. The prevalence of nicotine physical dependence diagnosed by using DSM-IV criteria for nicotine withdrawal was 2.4% in alcohol-dependent individuals, whereas only 0.3% of nondrinkers or social drinkers exhibited nicotine physical dependence. These results indicate to us that the potential for nicotine physical dependence is not much stronger than that reported among current smokers.

Adult↗
PubMed2001

The effects of lidocaine on nitric oxide production from an activated murine macrophage cell line.

UNLABELLED: Nitric oxide (NO), overproduced by activated macrophages, is important in the pathogenesis of various diseases, including septic shock and inflammatory tissue injury, as well as antibacterial host defense mechanisms. We examined the effects of lidocaine on NO production and the expression of inducible NO synthase (iNOS) protein and messenger RNA (mRNA) in activated macrophages. Murine macrophage-like cell line RAW 264 was stimulated for 8 h with lipopolysaccharide (10 mg/mL) and interferon-gamma (50 U/mL) in the presence of various concentrations of lidocaine (0-500 mg/mL). NO production was assessed by measuring levels of the stable metabolites, nitrite and nitrate (NOx), in the culture medium with an automatic analyzer using the Griess reaction. Expression of iNOS mRNA in harvested RAW 264 was quantified by Northern blot analysis using mouse iNOS complementary DNA probe. Expression of iNOS protein in the cells was assessed by Western blot analysis using anti-iNOS antibody. Lidocaine dose-dependently attenuated the increase in NOx levels in response to the stimulants. The drug at any concentration failed to decrease iNOS mRNA expression in RAW 264. Lidocaine at 500 mg/mL decreased iNOS protein levels. These data suggest that lidocaine reduced NO production in activated macrophages at multiple levels after transcription. The inhibitory site appeared to vary with the dose of lidocaine. IMPLICATIONS: Lidocaine dose-dependently inhibited nitric oxide production by activated macrophages, presumably at levels after transcription. The attenuating effect of lidocaine on organ injuries previously reported may be explained by the ability of the drug to suppress this inflammatory mediator.

Anesthetics, Local↗
PubMed2001

Therapeutic time-window of a group IIA phospholipase A2 inhibitor in rabbit acute lung injury: correlation with lung surfactant protection.

OBJECTIVE: We attempted to determine whether group IIA secretory phospholipase A2 (sPLA2-IIA) blockade after the onset of lung injury exerted therapeutic efficacy in the treatment of oleic acid (OA)-induced acute lung injury by using S-5920/LY315920Na, a novel specific inhibitor of sPLA2-IIA, with special interest in the changes of lung surfactant. DESIGN: Prospective animal study. SETTING: University laboratory. SUBJECTS: Forty Japanese white rabbits. INTERVENTIONS: The rabbits, under anesthesia, were endotracheally intubated and mechanically ventilated and then were divided into the following groups: OA + vehicle groups, intravenous infusion of OA for the first 2 hrs (0.1 mL x kg(-1) x hr(-1)) with the addition of vehicle (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); OA + S-5920/LY315920Na groups, treated identically to the OA control with the addition of S-5920/LY315920Na (1 mg/kg bolus followed by infusion at 0.5 mg x kg(-1) x hr(-1)) after OA (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); saline control groups, treated with saline instead of OA with the addition of vehicle (1 hr after OA administration, 4 rabbits). Arterial blood gas, lung mechanics, lung inflammation, lung surfactant phospholipids, and production of inflammatory mediators in the lung were measured. MEASUREMENTS AND MAIN RESULTS: Treatment with S-5920/LY315920Na 1 hr after OA infusion, but not 2 hrs after infusion, significantly attenuated the lung injury, as estimated by hypoxemia, decreased lung compliance, pulmonary edema, and vascular permeability. The therapeutic efficacy was similar to that found in our previous pretreatment study. The treatment after 1 hr dramatically inhibited OA-induced surfactant degradation in the bronchoalveolar lavage fluid (BALF), without affecting the concentrations of thromboxane A2, leukotriene B4, and interleukin-8 in BALF. The degree of surfactant degradation in BALF paralleled well with the severity of the lung injury. Furthermore, recombinant human sPLA2-IIA reproduced the similar hydrolysis pattern of isolated surfactant in vitro, which was inhibited by S-5920/LY315920Na. CONCLUSIONS: Our results indicate that therapeutic blockade of sPLA2-IIA ameliorated lung dysfunction via protection of surfactant degradation in an animal model of acute lung injury, and they suggest a new strategy in treating clinical acute lung injury.

Acetates↗
PubMed2000

Coordinate induction of collagenase-1, stromelysin-1 and urokinase plasminogen activator (uPA) by the 120-kDa cell-binding fibronectin fragment in fibrocartilaginous cells: uPA contributes to activation of procollagenase-1.

Specific fibronectin (Fn) fragments found in synovial fluid of arthritic joints potentially contribute to the loss of cartilage proteoglycans by inducing matrix metalloproteinase (MMP) expression. However, whether or not the Fn fragment-modulated changes in expression of MMPs result in a net increase in matrix-degradative activity through alterations in the balance between MMP activation and inhibition has not been established. To understand the mechanisms by which proteolytic Fn fragments may contribute to joint degeneration, conditioned medium from fibrocartilaginous cells exposed to Fn, its 30-kDa fragment containing the collagen/gelatin-binding domain, its 120-kDa fragment containing the central cell-binding domain, and the RGD peptide were assayed for MMPs, and MMP activators and inhibitors. We found that the 120-kDa fragment of Fn (but not intact Fn), the 30-kDa fragment, and the RGD peptide, dose-dependently induced procollagenase-1 and prostromelysin-1 and decreased levels of the tissue inhibitor of metalloproteinases (TIMPs) -1 and -2. The alpha5beta1 integrin was implicated in the induction of collagenase by the 120-kDa Fn fragment, since collagenase induction was abrogated in the presence of blocking antibody to this integrin. Conditioned medium from cells exposed to the 120-kDa Fn fragment also demonstrated increased levels of the activated collagenase-1, which resulted in significantly elevated collagen degradative activity. That the urokinase plasminogen activator (uPA) was involved in the activation of procollagenase-1 was suggested by findings that the 120-kDa Fn fragment induced uPA coordinately with procollagenase-1, and the activation of procollagenase-1 was dose-dependently inhibited in the presence of plasminogen activator inhibitor-1. These data demonstrate that the 120-kDa cell-binding fragment of Fn induces a net increase in matrix-degradative activity in fibrocartilaginous cells by concomitantly inducing MMPs and their activator, uPA, while decreasing TIMPs.

Animals↗
PubMed2000

A comparison of rabeprazole, lansoprazole, and ranitidine for improving preoperative gastric fluid property in adults undergoing elective surgery.

UNLABELLED: Acid aspiration syndrome at the induction of anesthesia is still a potentially life-threatening complication. Its severity is affected by both pH and volume of the gastric juice that is aspirated. We compared the effects of rabeprazole (a new proton pump inhibitor), lansoprazole, and ranitidine on gastric fluid properties in a prospective, randomized, double-blinded fashion in 180 adult patients undergoing elective surgery. Patients were divided into six groups (n = 30 in each) according to their premedication. Patients in each group received placebo-rabeprazole (PLA-RAB), rabeprazole-placebo (RAB-PLA), rabeprazole-rabeprazole (RAB-RAB), lansoprazole-lansoprazole (LAN-LAN), placebo-ranitidine (PLA-RAN), or placebo-placebo (PLA-PLA) for the first-second medication. Each dose of the study drug was 20 mg for rabeprazole, 30 mg for lansoprazole, and 150 mg for ranitidine. The first medication was given orally at 9:00 PM on the day before surgery and the second at 5:30 AM on the day of surgery. Each patient fasted overnight and took the drug with 20 mL of water. After tracheal intubation, gastric fluid was aspirated via an orogastric tube, and the volume and pH of the aspirate was measured. Preoperative gastric fluid acidity and volume were improved by the study drugs in the following order: PLA-RAN (pH 5.3, volume 0.10 mL/kg), RAB-RAB, LAN-LAN, PLA-RAB, and RAB-PLA (pH 3.8, volume 0.22 mL/kg). The proportion of patients at risk of acid aspiration syndrome according to the traditional criteria (pH < 2.5 and volume > 0.4 mL/kg) was minimized in Groups RAB-RAB and PLA-RAN (0%). We concluded that a single morning dose of ranitidine rather than two doses (bedtime and morning) of rabeprazole was the most effective premedicant to control gastric fluid properties and to minimize the risk of aspiration pneumonitis. IMPLICATIONS: Acid aspiration syndrome at the induction of anesthesia is rare but still a potentially life-threatening complication. We compared rabeprazole, lansoprazole, and ranitidine for reduction of preoperative gastric fluid acidity and volume in elective surgery and found that a combination of bedtime and morning doses of rabeprazole, or a morning dose of ranitidine, similarly minimized the variables. In adult patients who are at risk of aspirating gastric contents, improvement of gastric fluid environment by rabeprazole can reasonably be anticipated to provide protection against pneumonitis should regurgitation and aspiration of gastric contents occur.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Oral clonidine premedication does not change efficacy of simulated epidural test dose in sevoflurane-anesthetized children.

BACKGROUND: Caudal epidural anesthesia is often used as an adjunct to general anesthesia and for postoperative pain relief in children. In anesthetized children, epinephrine and isoproterenol are reliable indicators to detect accidental intravascular injection of a test dose. Oral clonidine, a useful premedicant in pediatric anesthesia, modifies hemodynamic responses to sympathomimetics, including catecholamines. The aim of the current study was to determine whether oral clonidine premedication alters the efficacy of a simulated intravascular test dose containing epinephrine or isoproterenol in sevoflurane-anesthetized children. METHODS: One hundred twenty children (aged 1-7 yr) were randomly divided into six groups; control-saline, control-epinephrine, control-isoproterenol, clonidine-saline, clonidine-epinephrine, and clonidine-isoproterenol. The three clonidine groups received oral clonidine 4 microg/kg [DOSAGE ERROR CORRECTED] as premedication, whereas the three control groups did not receive any premedication. Anesthesia was maintained with sevoflurane at a level of 1.2 minimum alveolar concentration. After hemodynamics were stable, 0.1 ml/kg of 1% lidocaine containing epinephrine 0.5 mg/kg or isoproterenol 75 ng/kg was intravenously given to the two epinephrine or isoproterenol groups, respectively, to simulate intravascular injection of a test dose. The saline groups received saline alone instead of the test dose. Heart rate, blood pressure, and T-wave amplitude of electrocardiogram were recorded before and after administration of study drugs for subsequent analysis. RESULTS: Test solution containing epinephrine increased heart rate, systolic blood pressure, and T-wave amplitude. Oral clonidine had no effect on elevation of these variables in response to epinephrine. The isoproterenol-containing test dose produced a prominent increase in heart rate and a less pronounced increase in systolic blood pressure and T-wave amplitude. Oral clonidine also failed to modify isoproterenol-induced hemodynamic and T-wave changes. Calculated sensitivity and specificity of epinephrine or isoproterenol were all 100% based on a new heart rate criterion (positive if >/= 10 beats/min) and were unaltered by oral clonidine premedication. CONCLUSIONS: Epinephrine or isoproterenol is a reliable marker to detect accidental intravascular injection of a test dose with 100% sensitivity and specificity based on a new heart rate criterion in sevoflurane-anesthetized children. These data suggest that oral clonidine premedication does not alter the efficacy of a simulated epidural test dose containing epinephrine or isoproterenol.

Administration, Oral↗
PubMed2000

The effect of phosphodiesterase III inhibitors on human neutrophil function.

OBJECTIVES: Neutrophils play an important role in ridding the body of bacteria and cellular debris. Several neutrophil functions are thought to be regulated by inotropes that increase cellular levels of cyclic adenosine monophosphate, including phosphodiesterase (PDE) inhibitors. We have investigated the effect of amrinone, milrinone, and olprinone, type III PDE (PDE-III) inhibitors, on several human neutrophil functions. DESIGN: Prospective in vitro study. SETTING: Academic research laboratory. SUBJECTS: Neutrophils isolated from 12 healthy adult volunteers. INTERVENTIONS: We measured chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion concentration, and cyclic adenosine monophosphate levels in neutrophils in the absence and the presence (at clinically relevant concentrations, 10 times, and 100 times those concentrations) of amrinone, milrinone, or olprinone. We also measured reactive oxygen species production under the same condition in a xanthine-xanthine oxidase system MEASUREMENTS AND MAIN RESULTS: None of the PDE-III inhibitors impaired neutrophil chemotaxis or phagocytosis. Amrinone at clinically relevant or higher concentrations and milrinone at high concentrations reduced superoxide, hydrogen peroxide, and hydroxyl radical levels in neutrophils and in the xanthine-xanthine oxidase system. Olprinone did not have those effects, and none of the PDE-III inhibitors had an effect on intracellular calcium ion concentration or cyclic adenosine monophosphate production in neutrophils stimulated by a chemotactic factor. CONCLUSIONS: The ability of amrinone to scavenge reactive oxygen species at clinically relevant concentrations while not affecting neutrophil function suggests that the PDE inhibitor can be used without detriment in severely ill patients.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Attenuation of hyperoxia-induced diaphragmatic dysfunction with lidocaine in hamsters.

OBJECTIVE: Toxic free radicals cause dysfunction of respiratory muscles, probably leading to respiratory distress. Exposure to high concentrations of oxygen generates plenty of free radicals. Lidocaine scavenges the reactive molecules. The purposes of the current study were first to examine whether hyperoxia impairs diaphragmatic function, and second, to assess the effects of lidocaine on hyperoxia-induced diaphragmatic dysfunction, if developed. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Forty and 48 adult male Golden-Syrian hamsters (110-150 g) in parts I and II studies, respectively. INTERVENTION: In the part I study, hyperoxia for 5 and 6 days reduced diaphragmatic contractility and enhanced fatigue. In the part II study, hamsters were randomly allocated to one of six groups (n = 8 each): exposure to air for 6 days with saline (group A-S) or lidocaine infusion (group A-L), exposure to 100% oxygen for 5 days with saline (group 05-S) or lidocaine (group 05-L), and exposure to 100% oxygen for 6 days with saline (group 06-S) or lidocaine (group 06-L). Saline or lidocaine (2 mg/kg/hr) was subcutaneously given immediately before exposure to air or oxygen. Diaphragmatic contractility and fatigability were assessed in vitro using muscle strips excised from the costal diaphragms. Diaphragmatic levels of malondialdehyde (MDA), an index of free radical-mediated lipid peroxidation, were measured. These variables were compared between groups. MEASUREMENTS AND MAIN RESULTS: Twitch and tetanic tensions in groups 05-S and 06-S were reduced compared with group A-S. Tensions generated during fatigue trials were also decreased in groups 05-S and 06-S. MDA levels were elevated in diaphragms from these groups. In groups 05-L and 06-L, contractile dysfunction, deterioration of fatigability, and MDA formation in the diaphragm were attenuated. CONCLUSIONS: Lidocaine attenuated hyperoxia-induced diaphragmatic dysfunction assessed by contractile profiles and fatigability in hamsters. This beneficial effect may be attributable, in part, to inhibition of lipid peroxidation.

Animals↗
PubMed2000

Diclofenac and flurbiprofen with or without clonidine for postoperative analgesia in children undergoing elective ophthalmological surgery.

We conducted a prospective, randomized study to compare the efficacy of preoperative diclofenac, flurbiprofen, and clonidine, given alone, as well as the combination of diclofenac and clonidine, and flurbiprofen and clonidine in controlling postoperative pain in 125 children. The patients (ASA I, 2-12 years) undergoing elective ophthalmological surgery were allocated to one of five groups: rectal diclofenac 2 mg.kg(-1) following oral placebo premedication, i. v. flurbiprofen 1 mg.kg(-1) following placebo premedication, oral clonidine premedication, rectal diclofenac 2 mg.kg(-1) following clonidine, and i.v. flurbiprofen 1 mg.kg(-1) following clonidine. The children received clonidine (4 microg.kg(-1)) or placebo 105 min before anaesthesia. Diclofenac or flurbiprofen was given immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using a modified objective pain scale (OPS). No opioids were administered throughout the study. Rectal diclofenac 2 mg.kg(-1) i.v. flurbiprofen 1 mg.kg(-1), oral clonidine 4 microg.kg(-1) provided similar OPS scores and requirement for supplementary analgesics during 12 h after surgery. Combination of oral clonidine and one of these nonsteroidal analgesics minimized postoperative pain. Our findings suggest that this combined regimen may be a promising prophylactic approach to postoperative pain control in children undergoing ophthalmological surgery.

Administration, Oral↗
PubMed2000

[Anesthetic management in pediatric interventional cardiology].

Interventional cardiology (n = 108) and cardiac angiography (n = 481) procedures in pediatrics performed between January 1996 and December 1998 were reviewed. Means (SD) of duration of anesthesia for interventional cardiology and cardiac angiography were 245 (130) and 152 (48) minutes, respectively (P < 0.001). Incidences of long operations requiring over 6 hours of anesthesia were 12 and 0%, respectively (P < 0.001). Incidences of hemodynamic derangements were 17 and 2.9%, and catheter-related complications were 7.4 and 0.83%, respectively (P < 0.001). Incidences of ICU admission were 7.4 and 0.62% those of emergency surgery were 4.6 and 0%, and those of blood transfusion were 4.6 and 0%, respectively (P < 0.001). Incidences of cardiopulmonary resuscitation, and cardioversion were also higher in interventional cardiology (P < 0.05), and all these emergency cases were rescued successfully. The risk of cardiac angiography is higher compared with general surgery, and the risk of interventional cardiology is higher than cardiac angiography in pediatrics. This study reconfirms that anesthesiologists should play an active role in care of pediatric patients undergoing high-risk procedures outside the operating room.

Anesthesia, General↗
PubMed2000

Clinical studies on bronchial asthma caused by contact with hamsters.

Bronchial asthma induced by contact with hamsters and other small rodents is receiving higher attention from the medical profession not only because of the problem of laboratory animal allergies (LAA), but also because of increasing household allergens for asthma, since keeping these pets has become more common in Japanese homes. The present report describes our studies on the backgrounds of nine patients with asthma who kept Dzungarian Dwarf hamsters as household pets. The following features were recognized among patients with bronchial asthma induced by contact with hamsters: 1) earlier onset of symptoms than for keeping other household pets, at an average of 14.7 months or within 12 months in 78% of the cases following the start of pet keeping; 2) adults ranging from their late 30s to 40s who have children of primary school age; 3) dwelling in apartments; 4) relatively high level of serum IgE and ECP; 5) positive for both immediate and late type asthmatic responses on an inhaling induction test; and 6) rapid remission after the cessation of pet keeping.

Adult↗
PubMed1999

Effects of pranlukast hydrate on serum eosinophil cationic protein levels in patients with adult bronchial asthma.

Pranlukast hydrate (CAS 103177-37-3, ONO-1078) was administered to 20 patients with bronchial asthma, and examined the effects of this agent on serum eosinophil cationic protein (ECP) levels and peripheral blood eosinophil counts. The mean serum ECP level in the group comprised of patients with bronchial asthma was significantly higher than that in the control group comprised of healthy adults. In responders in whom improvement in asthmatic symptoms was observed, serum ECP levels were significantly decreased compared to the pretreatment values 4 weeks after commencement of pranlukast hydrate administration. However, there were no changes in non-responders. There was no correlation between serum ECP level and peripheral blood eosinophil count before administration of pranlukast hydrate. However, there was a correlation 4 weeks after administration was started. It is suggested that pranlukast hydrate inhibits eosinophilic activity in patients with bronchial asthma.

Adult↗
PubMed1999

The effects of clonidine and dexmedetomidine on human neutrophil functions.

UNLABELLED: Neutrophil functions are inhibited by various anesthetics. Clonidine and dexmedetomidine, alpha2-agonists, are often used as adjuncts to anesthesia. Thus, we conducted the current study to determine the effect of clonidine, dexmedetomidine, and xylazine at clinically (or veterinary anesthetically) relevant concentrations (and 10 and 100 times these concentrations) on several aspects of human neutrophil functions using an in vitro system. The three alpha2-agonists had no effects on chemotaxis, phagocytosis, or superoxide anion (O2-) production of neutrophils, except that the highest concentration of clonidine inhibited chemotaxis. Increases in intracellular calcium concentrations in neutrophils stimulated by chemotaxin were not influenced by clonidine, dexmedetomidine, or xylazine. Unchanged calcium concentrations may contribute to failure to modulate the neutrophil functions. In addition, these drugs did not scavenge O2- generated by the cell-free (xanthine-xanthine oxidase) system. This is the first report concerning the effect of clonidine or dexmedetomidine on human neutrophil functions. Our findings suggest that we may not have to take extra precautions in using the alpha2-agonists in patients with infection, but that we cannot expect these drugs to be prophylaxis against autotissue injuries whose pathogenesis includes activation of neutrophils. IMPLICATIONS: Neutrophils are involved in the antibacterial host defense system and autotissue injury. We found that clinically relevant concentrations of clonidine and dexmedetomidine do not affect chemotaxis, phagocytosis, or superoxide production by human neutrophils. These findings indicate that it may not be necessary to take special care in using alpha2-agonists in patients with infection, sepsis, or systemic inflammation.

Adjuvants, Anesthesia↗
PubMed1999

The effects of cimetidine, ranitidine, and famotidine on human neutrophil functions.

UNLABELLED: Neutrophil functions, which play an important role in the antibacterial host defense system, are inhibited by various anesthetics and surgical procedures. Histamine H2-receptor antagonists are perioperatively used as a prophylaxis against acid aspiration syndrome or stress ulceration. We examined the effect of cimetidine, ranitidine, and famotidine, at clinically relevant concentrations and at 10 and 100 times this concentration, on several aspects of human neutrophil function using an in vitro system. The three H2-receptor antagonists did not impair neutrophils' chemotaxis or phagocytosis. Cimetidine and famotidine inhibited superoxide (O2-) and hydrogen peroxide (H2O2) production of the neutrophils in a dose-dependent manner, although the inhibitory effects were minimal. In contrast, ranitidine failed to change O2- or H2O2 production of neutrophils. The three H2-receptor antagonists did not scavenge these reactive oxygen species generated by the xanthine-xanthine oxidase system. The increase in intracellular calcium concentrations in neutrophils by a stimulant were dose-dependently attenuated with cimetidine or famotidine. This decreasing effect of the drugs on [Ca2+]i in neutrophils may represent one of mechanisms responsible for inhibition of reactive oxygen species generation. IMPLICATIONS: Neutrophils play a pivotal role in the antibacterial host defense system and tissue injury. We found that cimetidine and famotidine slightly reduced the O2- or H2O2 production of neutrophils in a dose-dependent manner, although ranitidine failed to do so. At least ranitidine does not seem to have any deleterious effect on neutrophil function, which is clearly an important consideration in its use in severely ill patients.

Calcium↗