Search PubMed⌕ Search

Biomedical subjects

K Mikawa

Publications and source records attributed to K Mikawa.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effects of BKCa channels on the reduction of cytosolic Ca2+ in cGMP-induced relaxation of guinea-pig trachea.

1. In order to examine the mechanisms of cGMP-induced relaxation in airway smooth muscle, the effects of atrial natriuretic peptide (ANP) and 8-brom cGMP on muscle tone were studied by measuring isometric tension, while the effects on cytosolic Ca2+ concentrations were studied by measuring the spectra of fura-2 loaded in guinea-pig tracheal strips. 2. Atrial natriuretic peptide and 8-brom cGMP caused a concentration-dependent inhibition of spontaneous tone in the guinea-pig trachea. The relaxant effects of these agents on spontaneous tone were markedly suppressed in the presence of iberiotoxin (IbTX), a selective inhibitor of large-conductance Ca2(+)-activated K+ (BKCa) channels. Iberiotoxin (30 nmol/L) markedly affected the maximal effect induced by ANP and 8-brom cGMP and augmented EC70 values for ANP and EC50 values for 8-brom cGMP approximately 27- and 17-fold, respectively. The inhibitory effects of IbTX on relaxation induced by these agents were diminished in the presence of 1 mumol/L nifedipine, an antagonist of voltage-operated Ca2+ channels (VOCC). 3. The inhibitory action of ANP and 8-brom cGMP on spontaneous tone was not affected by the presence of 10 mumol/L glibenclamide, an inhibitor of ATP-sensitive K+ channels, and 100 nmol/L apamin, an inhibitor of small-conductance Ca2(+)-activated K+ channels. When these agents were applied to tissues precontracted by high (40 mmol/L) K+, the relaxant effects of these agents markedly diminished. 4. The extracellular Ca2(+)-dependent contraction was inhibited in the presence of 0.3 mumol/L ANP or 0.1 mmol/L 8-brom cGMP. Concentration-response curves to extracellular Ca2+ (0.03-2.4 mmol/L) were markedly diminished by exposure to these agents. The maximal effect induced by extracellular Ca2+ was affected by these agents. 5. Atrial natriuretic peptide caused an inhibition of spontaneous tone accompanied by a reduction in the intracellular Ca2+ concentration. In the presence of IbTX, the elimination of both muscle tone and cytosolic Ca2+ by ANP was suppressed. 6. We conclude that ANP and 8-brom cGMP activate BKCa channels and that the inhibition of Ca2+ influx through VOCC, mediated by BKCa channel activation, may be involved in cGMP-dependent bronchodilation.

Animals↗
PubMed1997

[Reduction of alcohol consumption and its effect on Na(+)-K(+)-ATPase activity of red blood cell membrane].

Fifty-four untreated, mildly hypertensive men who were civil servants and were aged 30-59 years reduced their alcohol consumption as much as possible for three weeks. Then blood pressure and serum gamma GTP decreased significantly, but Na(+)-K(+)-ATPase activity of the red blood cell membrane did not change significantly. The enzyme activity in twenty subjects (45.5% of total subjects) increased and that in twenty-four subjects (54.5%) decreased or was unchanged. No significant relationship between the ratio of the change of Na(+)-K(+)-ATPase activity and that of blood pressure or serum gamma GTP was observed.

Adult↗
PubMed1996

Prostaglandin E1 attenuates the hypertensive response to tracheal extubation.

PURPOSE: Tracheal extubation causes hypertension and tachycardia, which may cause imbalance between myocardial oxygen demand and supply in patients at risk of coronary artery disease. We conducted a randomized, controlled study to evaluate the effects of 0.05 or 0.1 microgram.kg-1.min-1 prostaglandin E1 (PGE1) iv on haemodynamic variables occurring during tracheal extubation and emergence from anaesthesia and compared them in patients receiving either lidocaine or saline. METHODS: Eighty ASA physical status 1 patients undergoing elective surgery were enrolled in the current study. Anaesthesia was maintained with sevoflurane 1.0%-2.5% (ET concentration) and nitrous oxide 60% in oxygen. Muscle relaxation was achieved with vecuronium. The patients were randomly assigned to receive one of four treatments (n = 20 each): saline (control), 0.05 microgram.kg-1.min-1 PGE1, 0.1 microgram.kg-1.min-1 PGE1, or 1 mg.kg-1 lidocaine. PGE1 was infused from completion of surgery until five minutes after tracheal extubation. Changes in heart rate (HR) and blood pressure (BP) were measured during and after tracheal extubation. RESULTS: In the control group, the HR, systolic BP, and diastolic BP increased during tracheal extubation. Administration of 0.1 microgram.kg-1.min-1 PGE1 and 1 mg.kg-1 lidocaine attenuated the increases in BP although 0.05 microgram.kg-1.min-1 PGE1 failed to do so. The inhibitory effect of the 0.1 microgram.kg-1.min-1 PGE1 on BP was similar to that of lidocaine 1 mg.kg-1 iv. The increase in HR was attenuated by lidocaine but not by PGE1. CONCLUSION: The intravenous infusion of 0.1 microgram.kg-1.min-1 PGE1 given during emergence from anaesthesia and tracheal extubation is a useful method for attenuating the hypertension associated with noxious stimuli during this period.

Adult↗
PubMed1996

Comparison of nicardipine, diltiazem and verapamil for controlling the cardiovascular responses to tracheal intubation.

We have compared the efficacy of three calcium channel blockers, nicardipine, diltiazem and verapamil, in attenuating the cardiovascular responses to laryngoscopy and intubation in 60 normotensive patients (ASA I) undergoing rapid sequence induction of anaesthesia with thiopentone and fentanyl. We also examined whether or not these blockers inhibited catecholamine release induced by intubation. The patients were allocated to one of four groups (n = 15 for each): saline (control), nicardipine 30 micrograms kg-1, diltiazem 0.2 mg kg-1 or verapamil 0.1 mg kg-1. Verapamil and the three other drugs were administered 45 s and 60 s before the start of direct laryngoscopy, respectively, in a double-dummy design. Anaesthesia was induced with thiopentone 4 mg kg-1 i.v. and fentanyl 2 micrograms kg-1 i.v. Tracheal intubation was facilitated with vecuronium 0.2 mg kg-1. During anaesthesia, ventilation was assisted or controlled with 1% isoflurane and 50% nitrous oxide in oxygen. Laryngoscopy lasting 30 s was attempted 2 min after administration of thiopentone and vecuronium. Patients receiving saline exhibited significant increases in systolic and diastolic arterial pressures (AP), heart rate (HR) and plasma concentrations of catecholamines associated with tracheal intubation. The increase in AP was attenuated in patients treated with any calcium channel blocker. The greatest effect was elicited by verapamil, which attenuated the increase in HR, although nicardipine seemed to enhance tachycardia. All three drugs failed to suppress the increase in plasma catecholamine concentrations in response to tracheal intubation. These findings suggest that bolus injection of verapamil 0.1 mg kg-1 was a more effective method of controlling hypertension and tachycardia associated with intubation than diltiazem 0.2 mg kg-1 or nicardipine 30 micrograms kg-1, and that these prophylactic effects were not caused by inhibition of the catecholamine response.

Adult↗
PubMed1996

Oral clonidine premedication reduces postoperative pain in children.

Clonidine is an effective preanesthetic medication in children, providing a preoperative sedative effect. The analgesic properties of the drug have been well documented in adults. The current study was designed to investigate the effect of oral clonidine given preoperatively on postoperative pain in children undergoing minor surgery. In a prospective, randomized, controlled clinical trial, 90 children aged 5-12 yr undergoing elective ophthalmic, urologic, and otologic surgery received placebo (control), clonidine 2 micrograms/kg, or clonidine 4 micrograms/kg. These drugs were administered 105 min before the estimated time of induction of anesthesia and followed by treatment with oral atropine 0.03 mg/kg 60 min before anesthesia. Anesthesia was induced and maintained with halothane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using an objective pain scale (OPS). Clonidine 4 micrograms/kg provided lower OPS (highest) scores during 12 h after surgery and reduced requirement for postoperative supplementary analgesic (diclofenac suppository) compared with the other two regimens. These data suggest that oral clonidine premedication (4 micrograms/kg) is a possible approach to facilitating postoperative analgesia in children undergoing minor surgery.

Administration, Oral↗
PubMed1996

A comparison of lansoprazole, omeprazole, and ranitidine for reducing preoperative gastric secretion in adult patients undergoing elective surgery.

Acid aspiration syndrome of induction of anesthesia is a life-threatening complication whose severity is affected by both pH and volume of the aspirated gastric juice. We compared the effects of two proton pump inhibitors (PPIs), lansoprazole and omeprazole, and an H2 blocker, ranitidine, on gastric secretion in a prospective, randomized, double-blind fashion in 200 adult patients of ASA physical status I undergoing elective surgery. The patients were divided into eight groups (n = 25 each) according to their premedication. The patients received lansoprazole-lansoprazole (Group L-L), lansoprazole-placebo (Group L-P), placebo-lansoprazole (Group P-L), omeprazole-omeprazole (Group O-O), omeprazole-placebo (Group O-P), placebo-omeprazole (Group P-O), placebo-ranitidine (Group P-R), or placebo-placebo (Group P-P), as the first and second medications. The dose of the study drug was 30 mg for lansoprazole, 150 mg for ranitidine, and 80 mg for omeprazole. The first medication was administered orally at 9:00 PM on the night before surgery and the second at 5:30 AM in the morning on the day of the 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 were measured. The pH of the aspirated gastric fluid was higher in Groups P-R, L-L, P-L, O-O, and O-P than in Group P-P (P < 0.05). The volume of the gastric contents was similar in Groups P-0 and P-P, and the other groups had smaller gastric volume than Group P-P (P < 0.05). Gastric fluid from patients in Group P-R was the least acidic (pH 6.1 +/- 1.2) and had the least volume (0.09 +/- 0.06 mL/kg). Group L-L was comparable with Group P-R in both pH and volume, whereas Groups P-L and O-O were similar to Group P-R only in volume. The proportion of patients at risk according to the traditional criteria (pH < 2.5 and volume 0.4 mL/kg) was significantly lower in Groups L-L (0%), P-L (4%), O-O (4%), and P-R (0%) than in Group P-P (48%) (P < 0.05). We concluded that two consecutive doses of lansoprazole or a morning dose of ranitidine seemed to be the most effective preanesthetic medication for reducing gastric acidity and volume.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Attenuation of cardiovascular responses to tracheal extubation: verapamil versus diltiazem.

We studied the effect of intravenous injection of verapamil (0.05 mg/kg or 0.1 mg/kg) on cardiovascular changes during tracheal extubation and emergence from anesthesia and compared the efficacy of the drug with that of diltiazem (0.2 mg/kg). Eighty patients (ASA physical status I) who were to undergo elective gynecological surgery were randomly assigned to one of four groups (n = 20 each): saline (control), 0.05 mg/kg and 0.1 mg/kg verapamil, and 0.2 mg/kg diltiazem. These medications were given 2 min before tracheal extubation. Anesthesia was maintained with 0.5%-1.8% isoflurane and 60% nitrous oxide in oxygen. Muscle relaxation was achieved with vecuronium. Changes in heart rate (HR) and arterial blood pressure (AP) were measured during and after tracheal extubation. In the control group, the HR and systolic and diastolic AP increased significantly during tracheal extubation. Both calcium channel blockers attenuated the increases in these variables. The inhibitory effect was greatest with verapamil 0.1 mg/kg, while the alleviative effect of verapamil 0.05 mg/kg was inferior to that of diltiazem 0.2 mg/kg. These findings suggest that a bolus injection of verapamil 0.1 mg/kg given 2 min before tracheal extubation is a more effective prophylactic for attenuating the cardiovascular changes associated with extubation than is diltiazem 0.2 mg/kg.

Adult↗
PubMed1996

Lidocaine attenuates hyperoxic lung injury in rabbits.

BACKGROUND: High concentrations of oxygen acute lung injury. Neutrophils are thought to play a pivotal role in the pathogenesis of this lung injury through the release of oxygen radicals, neutral proteases, and lysosomal enzymes. Lidocaine has been shown to inhibit neutrophil function. We examined whether intravenous pretreatment with lidocaine attenuated acute lung injury induced by hyperoxia. METHOD: Twenty-seven anaesthetized male rabbits were allocated to receive one of three treatments (n = 9 for each group): ventilation with 100% oxygen for 36 h with and without lidocaine treatment, and ventilation with air for 36 h without lidocaine. In the lidocaine-treated group, a single intravenous lidocaine 2 mg/kg was administered immediately after the initiation of exposure to 100% oxygen; thereafter, the lidocaine was infused at a rate of 2 mg.kg(-1).h(-1) for 36 h until the animals were sacrificed. Haemodynamics, PaO2, and lung mechanics were recorded during the ventilation period. After exposure, the lung mechanics and cell fraction in bronchoalveolar lavage fluid (BALF) were measured and analyzed, as was the concentration of activated complements, and cytokines in BALF. The lung wet-to dry- (W/D) weight ratio and albumin concentrations in BALF were analyzed as an index of pulmonary oedema. We also compared the chemiluminescence of neutrophils isolated from the pulmonary artery, and light microscopic findings, in the three groups. RESULTS: Pure oxygen for 36 h caused no significant changes in haemodynamics, lung mechanics, or PaO2/FiO2 ratio. However, hyperoxia significantly increased the lung W/D weight ratio, the influx of neutrophils into the lung, and BALF concentrations of C3a, C5a, TNF-alpha, IL-1 beta, and albumin. Lidocaine attenuated these increases (W/D ratio: 5.7 vs 5.1, %PMN: 19.2% vs 1.6%, C3a: 62 ng/dl vs 14 ng/dl, C5a: 7.9 ng/dl vs 4.1 nd/dl, TNF-alpha: 25 fmol/ml vs 2.8 fmol/ml, IL-1 beta: 36 fmol/ml vs 2.2 fmol/ml, and albumin: 9.5 mg/dl vs 2.8 mg/dl, all: P < 0.05). The chemiluminescence was increased in hyperoxic compared with in normoxic rabbits and lidocaine treatment attenuated the increase (opsonized zymosan stiluated: 3.7 x 10(6) cpm vs 2.3 x 10(6) cpm, P < 0.05). Exposure to 100% oxygen caused extensive morphologic lung damage which was lessened by lidocaine (lung injury score (mean): 3 vs 4, P < 0.05). CONCLUSION: These findings suggest that intravenous lidocaine has a prophylactic effect on initial hyperoxic lung injury (pulmonary vascular permeability, histopathological, and biochemical BALF changes) in rabbits. The effects of lidocaine on more severe lung injury (decreased oxygenation) caused by hyperoxia for 72 h deserve further study.

Albumins↗
PubMed1996

The efficacy of clonidine for reducing perioperative haemodynamic changes and volatile anaesthetic requirements in children.

BACKGROUND: Oral clonidine given as a premedicant in adults has been shown to reduce intraoperative inhalation anaesthetic requirements and provide perioperative haemodynamic stability. We conducted the current study to ascertain whether or not these beneficial effects of clonidine can be reproduced in children. METHODS: In a prospective, randomized, double-blind, controlled clinical trial, 60 children (ASA I) aged 5-11 yr, received placebo (control), 2 micrograms kg-1 clonidine, or 4 micrograms kg-1 clonidine orally 105 min before induction of anaesthesia. Anaesthesia was induced with halothane, nitrous oxide in oxygen via mask and maintained with halothane and 60% nitrous oxide in oxygen. The halothane concentration was titrated to the concentration required to maintain haemodynamic stability (defined as 20% of blood pressure (BP) and heart rate (HR)) for maintenance of anaesthesia. The end-tidal concentration of halothane was monitored throughout anaesthesia. On completion of surgery, nitrous oxide and halothane were discontinued. Following confirmation of recovery from anaesthesia and muscle relaxation, the endotracheal tube was removed. RESULTS: Higher inspired concentrations of halothane (%) were required in the control and 2 micrograms kg-1 clonidine-treated groups (mean SD: 1.1 +/- 0.2 and 1.0 +/- 0.2, respectively) than in the 4 micrograms kg-1 clonidine-treated group (0.6 +/- 0.1) for haemodynamic stability (P < 0.05). Clonidine, 4 micrograms kg-1, significantly reduced the intraoperative lability (coefficient of variation) of systolic and diastolic BP and HR compared with the other two regimens. CONCLUSION: Oral clonidine premedication at a dose of 4 micrograms kg-1 provided intraoperative haemodynamic stability and reduced anaesthetic requirements in children. However, we are unable to extrapolate these observations to younger children and infants.

Administration, Oral↗
PubMed1996

Purification and characterization of sulochrin oxidase from Penicillium frequentans.

Sulochrin oxidase, an enzyme catalyzing regio- and stereospecific phenol oxidative coupling reaction to form (+)-bisdechlorogeodin from sulochrin, was isolated from Penicillium frequentans CMI 96659. By chromatographies on DEAE-cellulose, hydroxyapatite, Phenyl-Sepharose, Mono P, Mono Q, and HPLC gel filtration columns, sulochrin oxidase was purified to apparent homogeneity. The purified enzyme had a molecular weight of 230 K as estimated by gel filtration and 110 K as estimated by sodium dodecylsulfate-polyacrylamide gel electrophoresis under denaturing conditions, suggesting that the active enzyme was a homodimer. The enzyme showed pI 4.0 and an optimum pH of 6. The enzyme activity was strongly inhibited by the copper-chelating reagent, diethyldithiocarbamate, and did not recover its full activity even after removing the inhibitor by dialysis. However, enzyme activity was fully restored by the addition of Cu2+. Thus, sulochrin oxidase is considered to be a copper protein. The enzyme showed high substrate specificity for benzophenone compounds such as sulochrin and dihydrogeodin.

Alcohol Oxidoreductases↗
PubMed1996

Monoclonal antibody against bovine Lactoferricin and its epitopic site.

Bovine lactoferricin (LFcin B) is a strong antimicrobial peptide derived from N-lobe of lactoferrin. To study the immunochemical and structural properties of LFcin B, monoclonal antibody (mAb) was prepared and the amino acid sequence concerning with the binding to mAb has been identified. Mice injected with LFcin B showed no production of antibody specific to this peptide, whereas those with LFcin B-KLH conjugate produced anti-LFcin B antibodies. None of the mAb reacted with bovine lactoferrin C-lobe, human lactoferrin or LFcin H. By the reactivity of the mAb against the peptides synthesized on cellulose membranes using SPOTs and against chemically modified derivatives of LFcin B, the antigenic determinant of LFcin B was identified to be the sequence of "QWR".

Amino Acid Sequence↗
PubMed1996

[Nitric oxide and the lung].

Many studies on nitric oxide (NO) as a messenger for biosignal transduction have recently been published. Endogenous NO is thought to play a pivotal role in homeostasis of the respiratory system and pulmonary circulation. As exhaled NO levels increase in patients with asthma or bronchiectasia, NO seems to be related to some pathological states in the respiratory organ. NO inhalation has been shown to be effective in attenuating pulmonary hypertension and desaturation in acute respiratory failure. Recent findings concerning NO in the lung were described in this review article.

Acute Disease↗
PubMed1995

Attenuation of the catecholamine response to tracheal intubation with oral clonidine in children.

We conducted a prospective, randomized, double-blind , controlled clinical trial to examine (1) whether plasma catecholamine (CA) concentrations increased in response to tracheal intubation in children, and (2) the effects of clonidine on the CA responses. Sixty children (ASA physical status I) aged 7-13 yr were allocated to one of three groups (n = 20 for each group): diazepam 0.4 x kg(-1) (active control), clonidine 2 micrograms x kg(-1), or clonidine 4 micrograms x kg(-1) po. These agents were administered 105 min before induction of anaesthesia followed by oral atropine 0.03 mg x kg(-1) given 60 min before anaesthesia which was induced with thiamylal 5 mg x kg(-1) and tracheal intubation was facilitated with vecuronium 0.2 mg x kg(-1). Laryngoscopy, lasting 30 sec, was attempted two minutes after administration of the induction agents. Serial values for blood pressure, heart rate, and venous plasma CA concentrations were compared among the three groups and with the respective preinduction measurements. Children receiving diazepam or clonidine 2 micrograms x kg(-1) showed remarkable increases in systolic and diastolic blood pressures, heart rate, and plasma CA concentrations in response to tracheal intubation (P < 0.05). The increases were similar for the two regimens. These haemodynamic and CA changes were smaller in children receiving clonidine 4 micrograms x kg(-1) (P < 0.005). The haemodynamic responses were positively correlated with the CA responses. These findings indicate that tracheal intubation following rapid sequence induction of anaesthesia in children provokes a reflex increase in sympathetic activity characterized by increased plasma CA concentrations, and that attenuation of the cardiovascular changes with a high oral dose of clonidine may be due to suppression of the increase in sympathetic activity evoked by the intubation.

Adolescent↗
PubMed1995

Oral clonidine premedication reduces vomiting in children after strabismus surgery.

This is a prospective randomized double-blind trial conducted to determine whether preoperative orally administered clonidine causes or potentiates postoperative vomiting in 140 children (3-12 yr) undergoing strabismus surgery. They were all inpatients and classified randomly into four groups (n = 35 each); placebo (control), diazepam 0.4 mg.kg-1, clonidine 2 micrograms.kg-1, and clonidine 4 micrograms.kg-1. These agents were administered 93-112 min (mean; 100 min) before the anticipated time of induction of anaesthesia. All children received inhalational anaesthesia with halothane and nitrous oxide in oxygen. Muscle relaxation in all patients was obtained with vecuronium and residual neuromuscular blockade was antagonized with neostigmine and atropine before tracheal extubation. Diclofenac suppository was prescribed to prevent postoperative pain. No opioids or postoperative antiemetics were administered. All children remained in hospital for two days postoperatively. The incidence and frequency of vomiting were compared in the groups with Kruskall-Wallis Rank test. Clonidine 4 micrograms.kg-1 caused a lower incidence and frequency of vomiting than did placebo and diazepam (incidence and frequency: 11% and 1.37% and 3, and 34% and 2 in clonidine 4 micrograms.kg-1, placebo, and diazepam, respectively; P < 0.05 for clonidine 4 micrograms.kg-1 vs placebo and diazepam). However, low-dose clonidine was ineffective. These data suggest that preanaesthetic medication with clonidine 4 micrograms.kg-1 may be useful for preventing emesis following strabismus surgery. This property of clonidine indicates that it may be superior to other sedative premedicants such as diazepam and midazolam.

Administration, Oral↗
PubMed1995

Lansoprazole reduces preoperative gastric fluid acidity and volume in children.

The purpose of this study was to explore the efficacy of lansoprazole, a proton pump inhibitor, in reducing the acidity and volume of gastric aspirate in children immediately following the induction of anaesthesia. One hundred healthy in-patients aged 3-11 yr undergoing elective surgery were randomly allocated to four groups (n = 25 each): lansoprazole-lansoprazole, placebo-placebo, placebo-lansoprazole, and lansoprazole-placebo. For each treatment regimen, the first medication was administered at 9:00 pm on the night before surgery and the second at 5:30 am on the morning of the day of surgery (three hours preoperatively). The dose of lansoprazole was 30 mg (approximately 1.4 mg.kg-1 mean). Children were offered 10 ml.kg-1 apple juice three hours before induction of anaesthesia. After induction of anaesthesia and tracheal intubation, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube and analyzed for pH and total fluid volume. Lansoprazole increased gastric fluid pH and decreased gastric fluid volume regardless of whether it was administered before or after placebo. Two consecutive doses of lansoprazole was the most effective means of increasing the pH and reducing the volume of gastric aspirate; in this group, there were no subjects with gastric aspirate volume > 0.4 ml.kg-1 and pH < 2.5. Oral lansoprazole, at least 30 mg, given on the night before surgery or on the morning of surgery will improve the gastric environment at the time of induction of paediatric anaesthesia. The most effective regimen was two doses (at bedtime and on the morning) of lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗