Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 40
Filter
1.
Comput Methods Biomech Biomed Engin ; 23(10): 611-626, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32310682

ABSTRACT

In our previous works, the transport of activated platelets (APs) on orifice flow has been simulated by finite difference method (FDM). And the distribution of AP concentration on the flow was obtained. However, the effect of platelet aggregation on the distribution of AP concentration can't be investigated by FDM because FDM can't simulate platelet aggregation. On the other hand, platelet aggregation has been simulated by dissipative particle dynamics (DPD). In this paper, a hybrid method combining FDM and DPD is proposed to investigate the effect of platelet aggregation on the distribution of AP concentration. And the hybrid method is used to simulate thrombus formation on orifice flow. As for the effect of platelet aggregation, it is found that the distribution of AP concentration in the hybrid method is different from the distribution in FDM at the places of platelet aggregation. It is considered that the difference is induced by platelet aggregation. As for the distribution of thrombus, higher AP concentration and more aggregated APs are found around the reattachment point and in the recirculation area. It is considered that thrombus is mainly distributed at these places in the simulation. And according to our previous experimental results, thrombus is mainly distributed around the reattachment point and in the recirculation area. It is concluded that the effect of platelet aggregation on the distribution of AP concentration can be investigated by the hybrid method, and the computational results agree with our previous experimental results.


Subject(s)
Algorithms , Blood Circulation , Computer Simulation , Thrombosis/blood , Blood Platelets/pathology , Humans , Platelet Aggregation/drug effects
2.
J Dev Orig Health Dis ; 10(5): 536-541, 2019 10.
Article in English | MEDLINE | ID: mdl-30774066

ABSTRACT

Although maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are related to fetal growth, there is a paucity of data regarding how offspring sex affects the relationship between maternal BMI in underweight mothers (pre-pregnancy BMI <18.5 kg/m2) and size for gestational age at birth. The aim of this study was to investigate the effect of offspring sex on the relationships among maternal pre-pregnancy BMI, GWG and size for gestational age at birth in Japanese underweight mothers. Records of women with full-term pregnancies who underwent perinatal care at Kawasaki Municipal Hospital (Kawasaki, Japan) between January 2013 and December 2017 were retrospectively reviewed. The study cohort included underweight (n=566) and normal-weight women (18.5 kg/m2⩽pre-pregnancy BMI<25 kg/m2; n=2671). The incidence of small for gestational age (SGA) births in the underweight group was significantly higher than that in the normal-weight group (P<0.01). Additionally, SGA incidence in the underweight group was significantly higher than that in the normal-weight group (P<0.01) in female, but not male (P=0.30) neonates. In the women with female neonates, pre-pregnancy underweight was associated with a significantly increased probability of SGA (odds ratio [OR]: 1.80; P<0.01), but inadequate GWG was not (OR: 1.38; P=0.11). In contrast, in women with male neonates, inadequate GWG was associated with a significantly increased probability of SGA (OR: 1.53; P=0.03), but not with pre-pregnancy underweight (OR: 1.30; P=0.10). In conclusion, the present results suggest that pre-pregnancy underweight is associated with SGA in female offspring but not in male offspring.


Subject(s)
Birth Weight , Fetal Development , Gestational Weight Gain , Infant, Small for Gestational Age/growth & development , Thinness/physiopathology , Adult , Female , Gestational Age , Humans , Infant, Newborn , Japan , Male , Pregnancy , Retrospective Studies , Risk Factors , Sex Factors
3.
Br J Pharmacol ; 149(5): 573-80, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17001304

ABSTRACT

BACKGROUND AND PURPOSE: It has been postulated that isoflurane, a volatile anaesthetic, produces vasodilatation through activation of ATP-sensitive K+ (KATP) channels. However, there is no direct evidence for the activation of vascular KATP channels by isoflurane. This study was conducted to examine the effect of isoflurane on vascular KATP channels and compare it with that on cardiac KATP channels. EXPERIMENTAL APPROACH: Effects of isoflurane on KATP channels were examined in aortic smooth muscle cells and cardiomyocytes of the mouse using patch clamp techniques. Effects of the anaesthetic on the KATP channels with different combinations of the inward rectifier pore subunits (Kir6.1 and Kir6.2) and sulphonylurea receptor subunits (SUR2A and SUR2B) reconstituted in a heterologous expression system were also examined. KEY RESULTS: Isoflurane increased the coronary flow in Langendorff-perfused mouse hearts in a concentration-dependent manner, which was abolished by 10 microM glibenclamide. In enzymically-dissociated aortic smooth muscle cells, isoflurane evoked a glibenclamide-sensitive current (i.e. KATP current). In isolated mouse ventricular cells, however, isoflurane failed to evoke the KATP current unless the KATP current was preactivated by the K+ channel opener pinacidil. Although isoflurane readily activated the Kir6.1/SUR2B channels (vascular type), the volatile anesthetic could not activate the Kir6.2/SUR2A channels (cardiac type) expressed in HEK293 cells. Isoflurane activated a glibenclamide-sensitive current in HEK293 cells expressing Kir6.2/SUR2B channels. CONCLUSION AND IMPLICATIONS: Isoflurane activates KATP channels in vascular smooth muscle cells and produces coronary vasodilation in mouse hearts. SUR2B may be important for the activation of vascular-type KATP channels by isoflurane.


Subject(s)
ATP-Binding Cassette Transporters/physiology , G Protein-Coupled Inwardly-Rectifying Potassium Channels/physiology , Isoflurane/pharmacology , Potassium Channels, Inwardly Rectifying/physiology , Potassium Channels/physiology , Receptors, Drug/physiology , ATP-Binding Cassette Transporters/genetics , Anesthetics, Inhalation/pharmacology , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiology , Cell Line , Cells, Cultured , Coronary Circulation/drug effects , Dose-Response Relationship, Drug , G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics , Glyburide/pharmacology , Humans , In Vitro Techniques , Membrane Potentials/drug effects , Membrane Potentials/physiology , Mice , Mice, Inbred C57BL , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/physiology , Patch-Clamp Techniques/methods , Pinacidil/pharmacology , Potassium Channels/genetics , Potassium Channels, Inwardly Rectifying/genetics , Receptors, Drug/genetics , Sulfonylurea Receptors , Theophylline/pharmacology , Transfection/methods , Vasodilation/drug effects
5.
Circ Res ; 88(6): 570-7, 2001 Mar 30.
Article in English | MEDLINE | ID: mdl-11282890

ABSTRACT

-ATP-sensitive potassium (K(ATP)) channels were discovered in ventricular cells, but their roles in the heart remain mysterious. K(ATP) channels have also been found in numerous other tissues, including vascular smooth muscle. Two pore-forming subunits, Kir6.1 and Kir6.2, contribute to the diversity of K(ATP) channels. To determine which subunits are operative in the cardiovascular system and their functional roles, we characterized the effects of pharmacological K(+) channel openers (KCOs, ie, pinacidil, P-1075, and diazoxide) in Kir6.2-deficient mice. Sarcolemmal K(ATP) channels could be recorded electrophysiologically in ventricular cells from Kir6.2(+/+) (wild-type [WT]) but not from Kir6.2(-/-) (knockout [KO]) mice. In WT ventricular cells, pinacidil induced an outward current and action potential shortening, effects that were blocked by glibenclamide, a K(ATP) channel blocker. KO ventricular cells exhibited no response to KCOs, but gene transfer of Kir6.2 into neonatal ventricular cells rescued the electrophysiological response to P-1075. In terms of contractile function, pinacidil decreased force generation in WT but not KO hearts. Pinacidil and diazoxide produced concentration-dependent relaxation in both WT and KO aortas precontracted with norepinephrine. In addition, pinacidil induced a glibenclamide-sensitive current of similar magnitude in WT and KO aortic smooth muscle cells and comparable levels of hypotension in anesthetized WT and KO mice. In both WT and KO aortas, only Kir6.1 mRNA was expressed. These findings indicate that the Kir6.2 subunit mediates the depression of cardiac excitability and contractility induced by KCOs; in contrast, Kir6.2 plays no discernible role in the arterial tree.


Subject(s)
Adenosine Triphosphate/physiology , Potassium Channels, Inwardly Rectifying , Potassium Channels/physiology , Adenosine Triphosphate/pharmacology , Adenoviridae/genetics , Animals , Aorta/drug effects , Aorta/physiology , Blood Pressure/drug effects , Blotting, Northern , Diazoxide/pharmacology , Dose-Response Relationship, Drug , Electrophysiology , Genetic Vectors/genetics , Genotype , Glyburide/pharmacology , Heart/drug effects , Heart/physiology , Heart Rate/drug effects , Heart Ventricles/cytology , Heart Ventricles/drug effects , In Vitro Techniques , Membrane Potentials/drug effects , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , Norepinephrine/pharmacology , Pinacidil/pharmacology , Potassium Channels/drug effects , Potassium Channels/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transfection , Vasoconstriction/drug effects , Vasodilator Agents/pharmacology , Ventricular Function
6.
Br J Pharmacol ; 131(7): 1363-72, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11090108

ABSTRACT

1. We investigated the effects of JTV-519 (4-[3-(4-benzylpiperidin-1-yl)propionyl]-7-methoxy-2,3,4, 5-tetrahydro-1,4-benzothiazepine monohydrochloride), a novel cardioprotective drug, on the repolarizing K(+) currents in guinea-pig atrial cells by use of patch-clamp techniques. We also evaluated the effects of JTV-519 on experimental atrial fibrillation (AF) in isolated guinea-pig hearts. 2. In atrial cells stimulated at 0.2 Hz, JTV-519 in concentrations of 0.3 and 1 microM slightly prolonged the action potential duration (APD). The drug also reversed the action potential shortening induced by the muscarinic agonist carbachol in a concentration-dependent manner. 3. The muscarinic acetylcholine receptor-operated K(+) current (I(K.ACh)) was activated by the extracellular application of carbachol (1 microM), adenosine (10 microM) or by the intracellular loading of GTP gamma S (100 microM). JTV-519 inhibited the carbachol-, adenosine- and GTP gamma S-induced I(K.ACh) with the IC(50) values of 0.12, 2.29 and 2.42 microM, respectively, suggesting that the drug may inhibit I(K.ACh) mainly by blocking the muscarinic receptors. 4. JTV-519 (1 microM) inhibited the delayed rectifier K(+) current (I(K)). Electrophysiological analyses indicated that the drug preferentially inhibits I(Kr) (rapidly activating component) but not I(Ks) (slowly activating component). 5. In isolated hearts, perfusion of carbachol (1 microM) shortened monophasic action potential (MAP) and effective refractory period (ERP), and lowered atrial fibrillation threshold (AFT). Addition of JTV-519 (1 microM) inhibited the induction of AF by prolonging MAP and ERP. 6. We conclude that JTV-519 can exert antiarrhythmic effects against AF by inhibiting repolarizing K(+) currents. The drug may be useful for the treatment of AF in patients with ischaemic heart disease.


Subject(s)
Atrial Fibrillation/prevention & control , Cardiovascular Agents/pharmacology , Heart/drug effects , Membrane Potentials/drug effects , Potassium Channels/drug effects , Thiazepines/pharmacology , Action Potentials/drug effects , Adenosine/pharmacology , Animals , Atrial Fibrillation/physiopathology , Atrial Function , Calcium Channel Blockers/pharmacology , Carbachol/pharmacology , Dose-Response Relationship, Drug , Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology , Guinea Pigs , Heart/physiopathology , Heart Atria/cytology , Heart Atria/drug effects , In Vitro Techniques , Potassium Channels/physiology , Receptors, Muscarinic/physiology
7.
Br J Pharmacol ; 126(3): 751-61, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10188988

ABSTRACT

In order to clarify the mechanisms by which the class Ib antiarrhythmic drug aprindine shows efficacy against atrial fibrillation (AF), we examined the effects of the drug on the repolarizing K+ currents in guinea-pig atrial cells by use of patch-clamp techniques. We also evaluated the effects of aprindine on experimental AF in isolated guinea-pig hearts. Aprindine (3 microM) inhibited the delayed rectifier K+ current (IK) with little influence on the inward rectifier K+ current (IK1) or the Ca2+ current. Electrophysiological analyses including the envelope of tails test revealed that aprindine preferentially inhibits IKr (rapidly activating component) but not IKs (slowly activating component). The muscarinic acetylcholine receptor-operated K+ current (IK.ACh) was activated by the extracellular application of carbachol (1 microM) or by the intracellular loading of GTPgammaS. Aprindine inhibited the carbachol- and GTPgammaS-induced IK.ACh with the IC50 values of 0.4 and 2.5 microM, respectively. In atrial cells stimulated at 0.2 Hz, aprindine (3 microM) per se prolonged the action potential duration (APD) by 50+/-4%. The drug also reversed the carbachol-induced action potential shortening in a concentration-dependent manner. In isolated hearts, perfusion of carbachol (1 microM) shortened monophasic action potential (MAP) and effective refractory period (ERP), and lowered atrial fibrillation threshold. Addition of aprindine (3 microM) inhibited the induction of AF by prolonging MAP and ERP. We conclude the efficacy of aprindine against AF may be at least in part explained by its inhibitory effects on IKr and IK.ACh.


Subject(s)
Anti-Arrhythmia Agents/pharmacology , Aprindine/pharmacology , Heart Atria/drug effects , Membrane Potentials/drug effects , Potassium Channels/drug effects , Receptors, Muscarinic/physiology , Action Potentials/drug effects , Animals , Atrial Fibrillation/prevention & control , Atrial Function , Carbachol/pharmacology , Guinea Pigs , Heart Atria/cytology , Muscarinic Agonists/pharmacology , Patch-Clamp Techniques , Time Factors
8.
Neurourol Urodyn ; 17(6): 591-7, 1998.
Article in English | MEDLINE | ID: mdl-9829423

ABSTRACT

The male pelvic organs and the rhabdosphincter were visualized using magnetic resonance imaging (MRI) in five young male volunteers (mean age, 25.6 years). The prostate was crescent-shaped in three subjects and doughnut-shaped in two subjects. The external urethral sphincter (EUS) was located anterior to and lateral to the urethra but was rare on the rectal side. The membranous urethral length measured 28-35 mm (average, 31.0 mm). The pubourethral portion of the levator ani embraced the urinary bladder, the prostate, and the membranous urethra, and the most distal portion of the levator was thickened. During anal contraction, the EUS became thinner on both coronal and sagittal images and the levator was approximated closer to the urethra. Consequently, the prostate and the bladder base were elevated and the membranous urethra was elongated by 0-12mm (average, 5.6 mm). On sagittal images, the prostate, the membranous urethra, and the rectum were pulled closer to the pubic bone by anal contraction and the retropubic area became narrower. This study clearly demonstrated that MRI was useful in examining the anatomical configuration of the male pelvic floor and its dynamic movement during anal contraction.


Subject(s)
Magnetic Resonance Imaging , Pelvic Floor/anatomy & histology , Adult , Anal Canal/physiology , Humans , Male , Movement/physiology , Muscle Contraction/physiology , Muscle, Skeletal/anatomy & histology , Pelvic Floor/physiology , Prostate/anatomy & histology , Reference Values , Urethra/anatomy & histology , Urinary Bladder/anatomy & histology
9.
Cardiovasc Res ; 37(1): 179-86, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9539872

ABSTRACT

OBJECTIVE: The aim was to examine the effects of lysophosphatidylcholine (LPC), an amphiphilic lipid metabolite in ischemic myocardium, on intracellular pH (pH(i)) regulatory systems in guinea pig papillary muscles. METHODS: In CO2/HCO(3-)-buffered Tyrode solution, pH(i), intracellular Na+ activity (aNai) and membrane potential of isolated guinea pig papillary muscles were measured using ion-selective microelectrode and conventional microelectrode. Standard ammonium prepulsing with 20 mM NH4Cl was used to produce an intracellular acid load, and effects of LPC on the pH(i) recovery from acidosis were evaluated in the absence and presence of a transport inhibitor. RESULTS: LPC acidified the resting pH(i) by 0.03 +/- 0.01 pH units (n = 15, p < 0.01) concomitantly with a slight decrease in resting membrane potential and an increase in aNai in quiescent preparations. The pH(i) recovery rate from an intracellular acid load was decreased to 83 +/- 4% of the control value by 30 microM LPC (n = 8, P < 0.05) but not by 30 microM phosphatidylcholine (PC). In the presence of 10 microM 5-(N,N-hexamethylene) amiloride (HMA), a Na(+)-H+ exchange inhibitor, LPC still slowed pH(i) recovery from an intracellular acid load to 77 +/- 4% of the control (n = 5, P < 0.05). However, LPC failed to alter the pH(i) recovery rate in the presence of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 0.5 mM), a Na(+)-HCO3- symport inhibitor. CONCLUSION: LPC impairs Na(+)-HCO3- symport but not Na(+)-H+ exchange, and LPC may potentiate its arrhythmogenic action by intensifying the intracellular acidosis in ischemic myocardium.


Subject(s)
Intracellular Fluid/metabolism , Lysophosphatidylcholines/pharmacology , Myocardial Ischemia/metabolism , Myocardium/metabolism , 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology , Amiloride/analogs & derivatives , Amiloride/pharmacology , Animals , Carrier Proteins/antagonists & inhibitors , Guinea Pigs , Hydrogen-Ion Concentration , Membrane Potentials/drug effects , Papillary Muscles , Phosphatidylcholines/pharmacology , Sodium-Bicarbonate Symporters , Sodium-Hydrogen Exchangers/antagonists & inhibitors , Sodium-Hydrogen Exchangers/drug effects , Sodium-Hydrogen Exchangers/metabolism
10.
Eur J Pharmacol ; 338(1): 71-4, 1997 Oct 29.
Article in English | MEDLINE | ID: mdl-9408005

ABSTRACT

We examined the effects of pirmenol and disopyramide on the muscarinic acetylcholine receptor-operated K+ current (I[K.ACh]) in atrial cells and on experimental atrial fibrillation in isolated guinea-pig hearts. In isolated atrial myocytes, both pirmenol and disopyramide concentration-dependently inhibited the I(K.ACh) induced by carbachol or intracellular loading of GTPgammaS. Their inhibitory effects on the carbachol-induced current were more potent than those on GTPgammaS-induced current, suggesting that these drugs inhibit I(K.ACh) mainly by blocking muscarinic receptors. In Langendorff-perfused hearts these drugs reversed the carbachol-induced decreases in effective refractory periods and atrial fibrillation threshold. These drugs may be useful for the prevention of vagally induced atrial fibrillation.


Subject(s)
Anti-Arrhythmia Agents/pharmacology , Disopyramide/pharmacology , Heart/drug effects , Piperidines/pharmacology , Receptors, Muscarinic/drug effects , Action Potentials , Animals , Atrial Fibrillation/drug therapy , Carbachol/antagonists & inhibitors , Electric Stimulation , Guinea Pigs , Heart/physiology , Patch-Clamp Techniques , Potassium Channels/drug effects
11.
J Pharmacol Exp Ther ; 279(2): 617-24, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8930164

ABSTRACT

It is well known that amiodarone is effective for the treatment of atrial fibrillation. However, effects of amiodarone on the muscarinic acetylcholine receptor-operated K+ current (IK.ACh), which plays an important role in the repolarization of atrial action potential, have not been evaluated. This study was undertaken to determine whether amiodarone inhibits the acetyl-choline-sensitive muscarinic K+ (KACh) channel by use of the patch-clamp technique. In isolated guinea pig atrial cells, IK.ACh was activated by extracellular application of carbachol (1 microM) or adenosine (10 microM) or by the intracellular loading of GTP gamma S (100 microM). Amiodarone inhibited the IK.ACh activated in these three different ways with similar IC50 values around 2 microM, which indicated that amiodarone directly depresses the function of the KACh channel itself and/or GTP-binding proteins. Single KACh channel current was also recorded by use of a pipette solution containing carbachol (1 microM) or atropine (10 microM) plus theophylline (100 microM) in a cell-attached configuration. Amiodarone at a concentration of 3 microM significantly decreased the open probability of the KACh channel in both conditions. Amiodarone also reversed the carbachol- and adenosine-induced action potential shortening in a concentration-dependent manner. In isolated guinea pig hearts, perfusion of 1 microM carbachol shortened the effective refractory period of the atria and lowered the atrial fibrillation threshold. Addition of 10 microM amiodarone reversed these electrophysiological parameters to the control level. These results suggest that amiodarone inhibits IK.ACh by depressing the function of the KACh channel itself and/or associated GTP-binding proteins. This effect of amiodarone may at least in part be involved in the antiarrhythmic action against atrial fibrillation.


Subject(s)
Amiodarone/pharmacology , Anti-Arrhythmia Agents/pharmacology , Heart/drug effects , Potassium Channel Blockers , Receptors, Muscarinic/drug effects , Action Potentials/drug effects , Animals , Atrial Fibrillation/drug therapy , Carbachol/pharmacology , Guinea Pigs , Heart/physiology , Refractory Period, Electrophysiological/drug effects
12.
Artif Organs ; 20(6): 553-9, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8817954

ABSTRACT

This study proposes a method of predicting hemolysis induced by turbulent shear stress (Reynolds stress) in a simplified orifice pipe flow. In developing centrifugal blood pumps, there has been a serious problem with hemolysis at the impeller or casing edge; because of flow separation and turbulence in these regions. In the present study, hemolysis caused by turbulent shear stress must occur at high shear stress levels in regions near the edge of an orifice pipe flow. We have computed turbulent shear flow using the low-Reynolds number k-epsilon model. We found that the computed turbulent shear stress near the edge was several hundreds times that of the laminar shear stress (molecular shear stress). The peak turbulent shear stress is much greater than that obtained in conventional hemolysis testing using a viscometer apparatus. Thus, these high turbulent shear stresses should not be ignored in estimating hemolysis in this blood flow. Using an integrated power by shear force, it is optimal to determine the threshold of the turbulent shear stress by comparing computed stress levels with those of hemolysis experiments or pipe orifice blood flow.


Subject(s)
Blood Flow Velocity/physiology , Heart-Assist Devices/standards , Hemolysis , Erythrocytes/cytology , Fluid Shifts , Hemoglobins/analysis , Humans , Models, Theoretical , Rheology , Stress, Mechanical
13.
J Toxicol Sci ; 20(4): 383-93, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8531233

ABSTRACT

Pdn/+ female mice, mated with Pdn/+ males, were treated with 40 mg/kg body weight of all-trans-retinoic acid (RA) intraperitoneally on day 10 or 11 of gestation, and effects on the limb development were investigated. RA treatment induced the shortening of stylopodium and zygopodium. In the present experiment, we focused on the differences between genotypes in the shortening of stylopodium and zygopodium induced by RA. The effects of RA were milder in Pdn/Pdn than +/- (Pdn/+ and/or +/+) fetuses. The differences between genotypes in the effects of RA were more significant in the group treated on day 11 than on day 10 of gestation. Cartilage of stylopodium and zygopodium was longer in day-13 Pdn/Pdn embryos exposed to RA on day 11 of gestation than those in similarly treated +/- embryos. Many apoptotic cells were observed in the mesenchyme of the forelimb plates at 12 hr after injection of RA on day 11 of gestation. These results suggest that the Pdn gene might influence the apoptosis induced by RA in the mesenchymal cells of the limb, causing milder effects in the shortening of stylopodium and zygopodium in Pdn/Pdn fetuses.


Subject(s)
Extremities/embryology , Polydactyly/embryology , Tretinoin/toxicity , Animals , Apoptosis/drug effects , Female , Genotype , Gestational Age , Limb Deformities, Congenital , Male , Mice , Phenotype , Polydactyly/genetics , Polydactyly/pathology , Pregnancy
14.
J Emerg Med ; 13(1): 43-9, 1995.
Article in English | MEDLINE | ID: mdl-7782624

ABSTRACT

A case of tracheobronchomalacia (TBM) in a 71-year-old woman, who had suffered a cough syncope, is reported. It was a combination of both the crescent type (the posterior membranous portion of trachea or bronchus protrudes into the lumen) and the saber-sheath type (the lateral cartilaginous wall of trachea or bronchus protrudes into the lumen). In this patient, acute bronchitis had developed superimposed upon a chronic bronchitis in addition to age-related regressive changes of the trachea and bronchus. A TBM due to acute inflammation can be reversible, but aggressive airway management as well as medical treatment of the underlying inflammation are critical to a successful outcome.


Subject(s)
Bronchial Diseases/pathology , Cartilage Diseases/pathology , Tracheal Diseases/pathology , Acute Disease , Aged , Bronchi/pathology , Bronchial Diseases/diagnosis , Bronchial Diseases/etiology , Bronchitis/complications , Bronchography , Bronchoscopy , Cartilage Diseases/diagnosis , Cartilage Diseases/etiology , Female , Humans , Trachea/diagnostic imaging , Trachea/pathology , Tracheal Diseases/diagnosis , Tracheal Diseases/etiology
15.
Anesth Analg ; 79(4): 687-93, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7943776

ABSTRACT

Using standard microelectrode techniques, the effects of ketamine on the maximum rate of rise of action potential upstroke (Vmax) and the conduction velocity were examined and compared with the effects of quinidine, a sodium channel blocker, in isolated guinea pig papillary muscles. Both ketamine and quinidine decreased Vmax and the square of the conduction velocity in a concentration-dependent manner. The conduction slowing paralleled the decreases in Vmax, suggesting that the sodium current inhibition produced by these drugs is responsible for the conduction slowing. In the presence of quinidine, a train of stimulation after a quiescent period produced an exponential decline in Vmax, and the decrease in Vmax was enhanced by increasing stimulation frequency (i.e., use-dependent block). Ketamine significantly depressed Vmax of the first action potential after a long quiescent period (tonic block), and failed to produce a further decrease in Vmax during the subsequent train of stimulation. The decrease in Vmax was enhanced by simultaneous administration of ketamine and quinidine. Thus, ketamine decreases conduction velocity by inhibiting the sodium current. The mode of action on cardiac conduction is similar to that of quinidine, but different from that of volatile anesthetics which produce conduction slowing by impairing cell-to-cell coupling. However, ketamine produces a tonic block of the sodium channel while quinidine produces a use-dependent block. We conclude that ketamine should be administered with caution to patients receiving Class I antiarrhythmic drugs.


Subject(s)
Action Potentials/drug effects , Heart Conduction System/drug effects , Ketamine/pharmacology , Quinidine/pharmacology , Animals , Female , Guinea Pigs , Heart Conduction System/physiology , Male , Neural Conduction , Papillary Muscles/drug effects , Papillary Muscles/physiology
16.
Nihon Yakurigaku Zasshi ; 99(5): 353-62, 1992 May.
Article in Japanese | MEDLINE | ID: mdl-1592318

ABSTRACT

It has been presumed that a primary site of termination of the baroreceptor afferent was in the nucleus tractus solitarii (NTS). The intermediate region of the nucleus, located at the level of the obex, contains a large number of catecholamine neurons. The principal noradrenergic innervation of the NTS appears to arise from neurons of the so-called A2 group. It has been proposed that catecholamines released by A2 neurons serve to lower blood pressure and heart rate. We performed experiments to determine the effects of alpha-adrenoceptor agonists and antagonists on the baroreceptor reflex and alpha-adrenoceptor. Rabbits anesthetized with chloralose-urethane were injected with an alpha-adrenoceptor agonist, such as noradrenaline, phenylephrine or clonidine, into the NTS. An adrenoceptor-antagonist, such as yohimbine, phentolamine, prazosin or corynanthine was injected into the NTS of other anesthetized rabbits. Clonidine markedly lowered the blood pressure and heart rate, and it inhibited the baroreceptor reflex responses. Noradrenaline or phenylephrine did not lower the blood pressure and heart rate and scarcely inhibited the baroreceptor reflex. Yohimbine remarkedly inhibited the baroreceptor reflex responses; on the other hand, prazosin, corynanthine and phentolamine produced little inhibition of the responses. It is concluded that there are alpha 1- and alpha 2-receptors in the NTS of the rabbits, and the alpha 2-receptors play an important role in the neurotransmission in the NTS.


Subject(s)
Medulla Oblongata/drug effects , Pressoreceptors/drug effects , Reflex/drug effects , Sympathomimetics/pharmacology , Animals , Female , Male , Rabbits , Sympathomimetics/administration & dosage
17.
Nihon Yakurigaku Zasshi ; 99(1): 13-8, 1992 Jan.
Article in Japanese | MEDLINE | ID: mdl-1313777

ABSTRACT

Six new quinolones: enoxacin, norfloxacin, ofloxacin, ciproflosacin, lomefloxacin, and tosufloxacin and eight nonsteroidal anti-inflammatory drugs: fenbufen, flurbiprofen, ketoprofen, pranoprofen, ibuprofen, indomethacin, mefenamic acid and aspirin were tested for their ability to produce a central stimulating effect in mice. At 5 min after the oral administration of one of the nonsteroidal anti-inflammatory drugs, a new quinolone was administered orally. The combination of drugs induced convulsions in a dose-dependent manner, and some mice died as a result of the convulsions. The survival time was used as an index to measure the intensity of convulsions induced by the drug combination. The new quinolones in combination with fenbufen at 100 mg/kg produced convulsions in the following order of potencies: enoxacin greater than lomefloxacin greater than norfloxacin. In contrast, administration of fenbufen together with ofloxacin, ciprofloxacin, or tosufloxacin up to a dose of 1000 mg/kg caused no convulsions. Four nonsteroidal anti-inflammatory drugs combined with enoxacin at 100 mg/kg also caused convulsion dose-dependently. The order of potency in producing convulsion was as follows: fenbufen greater than flurbiprofen greater than ketoprofen = pranoprofen. However, no convulsions were produced by treatment of ibuprofen, indomethacin, mefenamic acid or aspirin together with enoxacin. From these results, the important chemical structures of the new quinolones particularly concerned with the appearance of convulsion were discussed.


Subject(s)
Anti-Bacterial Agents/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Quinolones/adverse effects , Seizures/chemically induced , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Dose-Response Relationship, Drug , Drug Interactions , Male , Mice , Quinolones/administration & dosage , Structure-Activity Relationship
18.
Nihon Yakurigaku Zasshi ; 99(1): 45-54, 1992 Jan.
Article in Japanese | MEDLINE | ID: mdl-1313778

ABSTRACT

A combination of fenbufen, a non-steroidal anti-inflammatory drug and the new quinolone produces a central stimulating action. To confirm the action, we used 6 kinds of new quinolones: enoxacin, norfloxacin, ofloxacin, ciprofloxacin, lomefloxacin and tosufloxacin in this experiment. The convulsive effects of these drugs were tested on the EEG recorded from the neocortex and subcortical regions of the rabbits. Animals treated with fenbufen (50-200 mg/kg, p.o.) tended to have a high amplitude slow wave in their EEG. Rabbits treated with the new quinolones at the dose of 100 mg/kg, p.o., with the exception of tosufloxacin, also tended to show a high amplitude slow wave in their EEG. Each new quinolone given 30 min after fenbufen (50 mg/kg, p.o.) elicited characteristic spikes on the EEG. Then, high-frequency-spikes and epileptiform seizure waves appeared for a long experimental period with this combination. The combination of fenbufen and tosufloxacin (100-400 mg/kg, p.o.) caused no changes in EEG and behavior. The spike and epileptiform wave could be suppressed only temporarily with diazepam (1-4 mg/kg, i.v.). These results suggest that combined use of fenbufen and one of the new quinolones, except for tosufloxacin, produces the seizure. Not only GABA but also several other mechanisms in the central nervous system may be involved in the convulsion.


Subject(s)
Anti-Bacterial Agents/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Electroencephalography/drug effects , Quinolones/adverse effects , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Drug Interactions , Female , Male , Quinolones/administration & dosage , Rabbits
19.
Food Chem Toxicol ; 30(1): 41-8, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1544605

ABSTRACT

The carcinogenic potential of gamma-oryzanol, a drug mainly used for the treatment of hyperlipidaemia, was studied in F344 rats. Groups of 50 males and 50 females were fed a diet containing 0 (control), 200, 600 or 2000 mg gamma-oryzanol/kg body weight/day for 2 yr. Although females in the highest dose group (2000 mg/kg body weight) showed a slight decrease in body weight at 104 wk, there were no treatment-related changes in general condition, food consumption, mortality, organ weight or haematology. Histopathological examination showed various tumours in all groups, including the control group. In the control and 2000-mg/kg groups, high tumour incidences were observed in the testes, pituitary and thyroid of males, and in the pituitary, uterus and mammary gland of females; however, there was no significant increase in the incidence of any tumours between the control and the 2000-mg/kg groups. The findings indicate that under the experimental conditions described gamma-oryzanol was not carcinogenic in F344 rats.


Subject(s)
Carcinogens/toxicity , Hypolipidemic Agents/toxicity , Neoplasms, Experimental/chemically induced , Phenylpropionates/toxicity , Administration, Oral , Animals , Body Weight/drug effects , Carcinogens/administration & dosage , Dose-Response Relationship, Drug , Female , Hypolipidemic Agents/administration & dosage , Hypolipidemic Agents/blood , Male , Organ Size/drug effects , Phenylpropionates/administration & dosage , Phenylpropionates/blood , Rats , Rats, Inbred F344
20.
Food Chem Toxicol ; 30(1): 49-56, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1544606

ABSTRACT

The carcinogenic potential of gamma-oryzanol, a drug mainly used for the treatment of hyperlipidaemia, was studied in B6C3F1 mice. Groups of 50 males and 50 females were fed a diet containing 0 (control), 200, 600 or 2000 mg gamma-oryzanol/kg body weight/day for 78 wk. No treatment-related changes were observed in general condition, body weight, food consumption, mortality, organ weight or haematology. Histopathological examinations showed various tumours in all groups, including the control group. In the control and 2000-mg/kg groups, relatively high tumour incidences were observed in the liver of males and in the haematopoietic organs of females. However, there was no statistically significant difference in the incidence of any tumours between the control and the 2000-mg/kg groups. The findings indicate that under the experimental conditions described gamma-oryzanol was not carcinogenic in B6C3F1 mice.


Subject(s)
Carcinogens/toxicity , Hypolipidemic Agents/toxicity , Neoplasms, Experimental/chemically induced , Phenylpropionates/toxicity , Administration, Oral , Animals , Body Weight/drug effects , Carcinogens/administration & dosage , Dose-Response Relationship, Drug , Female , Hypolipidemic Agents/administration & dosage , Male , Mice , Organ Size/drug effects , Phenylpropionates/administration & dosage
SELECTION OF CITATIONS
SEARCH DETAIL
...