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Biomedical subjects

M Endoh

Publications and source records attributed to M Endoh.

At least 307 records · Page 17Linked to original sources
PubMed1988

Actions of sympathomimetic amines on the Ca2+ transients and contractions of rabbit myocardium: reciprocal changes in myofibrillar responsiveness to Ca2+ mediated through alpha- and beta-adrenoceptors.

The effects of sympathomimetic amines on Ca2+ transients and isometric contractions were assessed in isolated rabbit papillary muscles in which multiple superficial cells had been microinjected with the calcium-sensitive bioluminescent protein aequorin. In the presence of beta-adrenoceptor blockade, the alpha-receptor agonist phenylephrine increased both the amplitude of the aequorin signals and the force of contraction in a concentration-dependent manner. However, the maximum increase in the aequorin signals was less than 10% of that produced by the beta-receptor agonist isoproterenol, while the maximum increase in force of contraction produced by alpha-stimulation was about 50% of that elicited via beta-adrenoceptors. For a given increase in the force of contraction, stimulation of alpha-adrenoceptors produced much less change in the amplitude of the aequorin signals than did elevation of the extracellular Ca2+ concentration; we interpret this to mean that the positive inotropic effect of alpha-adrenoceptor stimulation is in large part the result of an increase in myofibrillar sensitivity to Ca2+. Stimulation of alpha-adrenoceptors produced little change or a slight decrease in the duration of the aequorin signal and an increase in the duration of contraction, while stimulation of beta-adrenoceptors significantly decreased the time to peak and duration of both the aequorin signals and the contractions. For a given level of inotropic effect, high concentrations of isoproterenol often increased the aequorin signals more than did elevations of Ca2+, which is consistent with other evidence that the cyclic AMP-dependent phosphorylation of troponin I leads to a decrease in myofibrillar Ca2+ sensitivity. However, concentrations of isoproterenol that did not produce evidence of this sort of desensitization also abbreviated the contractions much more than they did the aequorin signals. This suggests that the traditionally accepted mechanisms--a decrease in the Ca2+ affinity of troponin C and an acceleration of Ca2+ uptake by the sarcoplasmic reticulum--may not be sufficient to account for the actions of beta-receptor stimulation on the time course of contraction. In the absence of blocking agents, the naturally occurring catecholamines norepinephrine, epinephrine, and dopamine appear to influence the function of the rabbit papillary muscle through both alpha- and beta-adrenoceptors. Dopamine has a relatively greater effect on alpha-adrenoceptors than the other catecholamines.

Animals↗
PubMed1988

Effect of chlorpromazine on the pharmacokinetics and pharmacodynamics of pentobarbital in rats.

The effects of chlorpromazine (4 mg/kg i.v.) on the disposition and duration of loss of the righting reflex (LRR, sleeping time) produced by intravenous pentobarbital (5 to 50 mg/kg) were studied in rats. The plasma concentration time profile following i.v. administration of pentobarbital alone was reasonably well described by a three compartment open model with Michaelis-Menten type elimination kinetics. The brain to plasma concentration ratio of pentobarbital was 1.5 and was almost constant during the experiment. Coadministration of chlorpromazine significantly reduced the systemic clearance of pentobarbital. Since pentobarbital is eliminated from the body mainly by hepatic metabolism, reduction of systemic clearance reflects the reduction of hepatic metabolism of pentobarbital. The hepatic intrinsic clearance of pentobarbital was decreased from 0.438 to 0.331 l/h by chlorpromazine coadministration. Hepatic blood flow was also decreased significantly, whereas the plasma protein binding and the distribution to the red blood cell were not appreciably altered. The profile of duration of LRR versus the logarithm of the dose of pentobarbital was linear over a 20 to 70 mg/kg dose range irrespective of chlorpromazine coadministration. The awakening plasma and brain concentrations of pentobarbital without chlorpromazine were estimated as 12.4 micrograms/ml and 17.8 micrograms/g, respectively. The sleeping time versus the logarithm of pentobarbital dose under chlorpromazine coadministration was shifted to the left and the slope of the linear portion was also decreased. There was no single value of awakening plasma or brain concentration. Plasma concentration at the end of the action decreased with decreasing dose. These facts indicated that the sensitivity of the central nervous system to pentobarbital might be increased by chlorpromazine. In conclusion, chlorpromazine inhibited the hepatic metabolism of pentobarbital, resulting in significant increases in plasma and brain concentrations. However, this pharmacokinetic change could not fully explain the pharmacodynamic alternation.

Animals↗
PubMed1988

Pharmacokinetic and pharmacodynamic studies of piretanide in rabbits. III. Sodium and potassium excretion under different hydrated conditions.

The diuretic effect of piretanide, one of the loop diuretics, was investigated in three different hydrated conditions, namely well hydrated condition (treatment I), progressive hydropenic condition (treatment II) and complete hydropenic condition (treatment III) in rabbits. Each rabbit received intravenous administration of 1.5 or 15 mg/kg of piretanide and the urine flow rate, the excretion rates of Na and K, plasma concentrations of Na and K, urine osmolarity, plasma concentration of piretanide and urinary excretion of piretanide were determined after administration. The pharmacokinetics of piretanide was not influenced by the hydration state of the body, even in treatment III. The diuretic effect of piretanide evaluated by both urine flow rate (EH2O) and Na+K excretion rate (ENa+K), was significantly affected by the hydration state of the body. The more the hydropenic state was developed, less amounts of urine or electrolytes were excreted. A pharmacokinetic-pharmacodynamic link model which was proposed in the previous paper was applied to the present experimental results. The result indicated that the diuretic effect, even in the complete hydropenic condition (treatment III), was reasonably described by the model, with minor modifications. The time course of the excretion rate of K (EK) was not always in parallel with ENa+K, but was dependent on treatments. We found that the K-fraction, which was known as an indicator of the Na-K exchange reaction in the distal tubule, was quantitatively related to ENa+K, using a simple equation. Accordingly, the time course of EK was also calculated. The result also indicated that time courses of EK were described reasonably well by the model, regardless of treatments and doses.

Animals↗
PubMed1988

A kinetic study of chlorpromazine on the hyperglycemic response in rats. I. Effect of chlorpromazine on plasma catecholamines.

The effect of chlorpromazine (0.5 and 4 mg/kg) on plasma catecholamines (adrenaline and noradrenaline) concentrations was investigated in rats. After an i.v. bolus administration of chlorpromazine, plasma adrenaline and noradrenaline concentrations showed a dose dependent increase. In order to clarify the pharmacokinetics of catecholamines in plasma, i.v. infusion of adrenaline or noradrenaline was also carried out. Plasma catecholamines after i.v. infusion showed typical characteristics of a one compartment model with a zero order production rate of endogenous catecholamines. From the data observed, a mathematical model was constructed to elucidate the relationship between the pharmacokinetics (brain concentrations) and the pharmacologic effect (plasma catecholamines concentrations) of chlorpromazine in rats. The results indicated that the time courses of plasma adrenaline and noradrenaline concentrations after an i.v. administration of chlorpromazine were described reasonably well by a simple pharmacokinetic-pharmacodynamic model.

Animals↗
PubMed1988

Pharmacokinetic and pharmacodynamic studies of piretanide in rabbits. II: Effects on the proximal tubules and the loop of Henle.

In order to clarify the effect of piretanide in the nephrons, pharmacokinetics and pharmacodynamics of piretanide were studied under a hydropenic condition in the rabbit. The hydropenic condition was developed by a simultaneous infusion of an antidiuretic hormone and hyperosmotic saline. Lithium was used as the indicator of the proximal sodium reabsorption. Plasma concentrations and urinary excretion rates of piretanide were not influenced by the hydration state of the body. The glomerular filtration rate (GFR) showed a long lasting decrease after piretanide administration; however, the urinary excretion rates of salts and water were increased prominently just after administration. The lithium clearance ratio, which was obtained by dividing the lithium renal clearance by GFR, indicated that piretanide inhibited the proximal reabsorption of sodium. The urine osmolarity after piretanide administration showed a significant decrease, and this indicated that the osmolarity of the renal medulla was also influenced by piretanide. From these observations, a model describing the transport of water and osmotic substances in the nephrons was constructed to calculate the effect of piretanide. The results indicated that the diuretic effect of piretanide in the hydropenic rabbit was reasonably described by the model. The model parameters obtained suggested that the site of action of piretanide in the proximal tubules might be in the peritubular side rather than inside the lumen, whereas the site of action in the loop of Henle might be inside the lumen.

Animals↗
PubMed1988

[Clinico-pathological study on recurrent gastric cancer after curative resection].

Among 675 patients who had undergone curative resection of gastric cancer during last 13 years, 113 died of cancer recurrence. One hundred and forty-five patients who had survived longer than 5 years were used as controls. In the recurrence group, the primary lesion was larger and the lymph node metastasis more common as compared with the surviving controls. Moreover, these lesions were often located at the upper third of the stomach and exhibited Borrmann 3 or 4 type. Prognostic serosal invasion was positive in 75 per cent of the recurrence group and negative in 84 per cent of the surviving controls. The most frequent mode of recurrence was hematogenous metastasis in negative prognostic serosal invasion (54%) and peritoneal disseminated metastasis in positive prognostic serosal invasion (52%). There were no differences in the distribution of gross and histological types of cancer in the modes of recurrence. It was found that peritoneal dissemination and/or local recurrence dominated as the mode of recurrence (51%), followed by hematogenous metastasis (34%), but that lymph node recurrence was uncommon (15%). In peritoneal disseminated cases, long-term survival following reoperation should not be expected. It was suggested that in order to improve the prognosis in the case of hematogenous metastasis, postoperative immunochemotherapy should be applied.

Adenocarcinoma↗
PubMed1988

Enantiomers of dobutamine increase the force of contraction via beta adrenoceptors, but antagonize competitively the positive inotropic effect mediated by alpha-1 adrenoceptors in the rabbit ventricular myocardium.

Experiments were carried out to characterize the pharmacological properties of enantiomers and racemic mixture of dobutamine to modulate the myocardial contractility through alpha and beta adrenoceptors in the rabbit papillary muscle. Dobutamine caused the concentration-dependent positive inotropic effect: the rank order of potency was R-(+)- greater than (+/-) - greater than S-(-)-dobutamine. The positive inotropic effect of (+)-, (-)- and (+/-)-dobutamine was antagonized by a beta adrenoceptor antagonist, (+/-)-bupranolol in a competitive manner, but was not affected by an alpha-1 adrenoceptor antagonist, prazosin. The concentration-response curve for (-)-phenylephrine mediated by alpha adrenoceptors in the presence of 10(-6) M (+/-)-bupranolol was shifted by enantiomers of dobutamine to the right in a concentration-dependent manner. Thus, enantiomers of dobutamine antagonized the positive inotropic effect of (-)-phenylephrine in a competitive manner, and pA2 values [negative logarithm of the dissociation constant (KB)] for (+)- and (-)-dobutamine were 6.67 and 5.99, respectively. The specific binding of [3H]prazosin to membrane fractions of rabbit ventricular myocardium was displaced by dobutamine with a high potency: the -log Ki values for (+)- and (-)-dobutamine were 6.43 and 5.97, respectively, which correspond well with pA2 values of these compounds for functional modification. These findings indicate that enantiomers of dobutamine elicit the positive inotropic effect through activation of beta adrenoceptors, whereas both enantiomers behave as the competitive antagonist of myocardial alpha adrenoceptors mediating the positive inotropic effect in the isolated rabbit papillary muscle.

Animals↗
PubMed1988

Mechanism of action of Bordetella heat-labile toxin on vascular smooth muscle strips and cells.

The mechanism of action of Bordetella heat-labile toxin (HLT) was analyzed in vitro using vascular smooth muscle strips (VSMS) and cultured cells (VSMC), from aortas of pig, guinea pig, rabbit, rat or mouse. HLT induced contractions to both VSMS and VSMC, but not other types of tissues and cells. HLT induced the increase of Ca2(+)-influx in parallel with the contraction. These HLT activities were not influenced by the addition of verapamil, diltiazem, or TMB-8, though a certain extension of the lag period was seen. The contractile action on VSMC was not influenced by a various blockers of cascades or systems. The HLT-induced contraction in VSMC was completely inhibited by H-7, but not by H-8. HLT did not induce specific activation of the protein kinases in VSMC. HLT induced the permeability changes in VSMS or VSMC membranes to cyclic nucleotides or trypan blue. Both HLT-induced contraction and permeability change were inhibited by dextran of M.W. 8,000. 125I-HLT bound immediately to VSMC depending on the HLT dose. At 37 degrees C, the binding ratio in maximum was approximately 0.8% of total HLT added at 60 min after exposure. At 4 degrees C, it was less than 20% of that at 37 degrees C. The labeled HLT binding to VSMC was released readily by washing. From these results, possible mechanism of HLT action was discussed.

Animals↗
PubMed1987

Experimental allergic encephalomyelitis mediated by murine encephalitogenic T cell lines specific for myelin proteolipid apoprotein.

T cell lines specific for bovine myelin proteolipid apoprotein (PLP) were established from SJL/J mice. The line cells bore surface phenotypes of T helper/inducer cells (Lyt-1+, Lyt-2-, L3T4+) and responded well to bovine, rat, and guinea pig PLP but not to myelin basic protein. One line responded to major PLP, and another responded to both major PLP and DM-20, which are the two major intrinsic membrane proteins of the central nervous system (CNS) myelin. Intraperitoneal inoculation of 4 to 30 X 10(6) PLP-activated line cells followed by injection of pertussis vaccine induced acute inflammatory disease of the CNS, with typical clinical signs of EAE mostly in a week in recipient mice that had been treated with low-dose irradiation. Almost all animals recovered completely, and two of the 12 animals relapsed 42 or 75 days after inoculation. The lesions were restricted to the CNS and were characterized by perivascular and parenchymal infiltration of inflammatory cells, fibrin deposit, and demyelination. In the severe lesions, axons were also damaged. These observations suggest that PLP is a definite encephalitogen, and PLP-sensitized effector T cells induce inflammatory demyelination in the CNS.

Animals↗
PubMed1987

DNA and immunoglobulin synthesis by rabbit peripheral blood lymphocytes in vitro: complete and incomplete stimulation.

Activation of resting (G0) rabbit peripheral blood lymphocytes (PBLs) into DNA synthesis and IgG synthesis was studied using sheep anti-rabbit IgG (SARIgG), protein A, pokeweed mitogen (PWM), and lipopolysaccharide (LPS). DNA synthesis was assayed by [125I]iododeoxyuridine incorporation. IgG synthesis was measured by determination of Ig in culture supernatants by an ELISA assay. Rabbit PBLs cultured with SARIgG or protein A for 48 hr and then without these reagents for 72 hr showed both DNA synthesis and Ig synthesis, whereas PWM and LPS had very little, if any, effect. PBLs stimulated with SARIgG for 6 hr and then without SARIgG for subsequent 114 hr did not become activated into DNA synthesis or IgG synthesis. However, PBLs prestimulated with SARIgG for 6 hr and then with PWM for 114 hr showed prominent DNA and IgG synthesis. LPS also maintained activation of PBLs after prestimulation of these cells with SARIgG, but the effect was much smaller than that of PWM. No evidence was found for production of factors by SARIgG-stimulated PBLs that could, by themselves, either stimulate resting cells or maintain activation of SARIgG-prestimulated cells. These results suggest that anti-IgG and protein A are complete activating mitogens for resting rabbit B cells to proliferate and differentiate into IgG-producing cells, whereas PWM and LPS are not able to activate G0 cells directly, but have a sustaining effect after activation of resting B cells with anti-IgG, either directly or via production of factors by accessory cells.

Animals↗
PubMed1987

Inotropic versus chronotropic, dromotropic, and coronary vasodilator actions of DPI 201-106, a novel positive inotropic agent, in the dog heart.

Inotropic versus chronotropic, dromotropic, and vascular effects of DPI 201-106 were assessed in isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. DPI 201-106 was administered intraarterially. In paced papillary muscles the drug produced an increase in developed tension. In spontaneously beating papillary muscles the drug slightly decreased the beating rate. In SA node preparations the drug decreased sinus rate, and atrial standstill ensued from the highest dose. In AV node preparations the drug affected AV conduction only when administered into the AV node artery, and in high doses second- or third-degree AV block occurred. In all preparations the drug increased blood flow. DPI 201-106 at the dose that produced a 50% increase in the force of contraction of ventricular muscle increased coronary blood flow by 8.4%, AV conduction time by 7.6%, and decreased sinus rate by 2.6%, indicating its high selectivity for force. When infused into the AV node artery, the drug in high doses produced dose-dependent prolongations of both the AV nodal conduction time and the functional refractory period of the AV node, which were pronounced with elevation of the pacing rate. These effects of DPI 201-106 are very similar to those of calcium channel blockers.

Animals↗
PubMed1987

Noradrenergic function and the dexamethasone suppression test in depression.

We measured the plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and the serum cortisol levels before and after the oral administration of dexamethasone. There was not a significant difference in the plasma free MHPG levels between the patients with major depression and normal subjects. There was a significant positive correlation between the plasma MHPG levels and postdexamethasone cortisol levels in patients with major depression. This indicates that there exists a certain relation between abnormalities of the central noradrenergic systems and hypothalamic-pituitary-adrenal axis in patients with major depression. The mean total scores of the Hamilton Rating Scale for Depression of the first (MHPG less than 5 ng/ml) and third (10 ng/ml less than or equal to MHPG) groups were significantly higher than those of the second (5 less than or equal to MHPG less than 10 ng/ml) group.

Depressive Disorder↗
PubMed1987

Modified open renal biopsy: results in 934 patients.

Nine hundred and thirty-four cases of open renal biopsy using the 'Kawamura-modified forceps' have been performed over the past 9 years under general anesthesia. Sufficient amounts of renal tissue for routine histology, immunofluorescence staining and electron microscopy were obtained in all 934 cases. There were no serious major complications attributable to the procedure. It is concluded that this procedure can be performed easier and faster than the previous technique of percutaneous renal biopsy, although patients undergoing open renal biopsy with the Kawamura-modified forceps have to be transferred to the operating room for this procedure.

Adolescent↗
PubMed1987

Pituitary-adrenocortical response to metoclopramide in patients with acromegaly and prolactinoma: a clinical evaluation of catecholamine-mediated adrenocorticotropin secretion.

We have demonstrated that metoclopramide stimulates cortisol secretion at least in part by a stress-mediated effect in normal men. To examine further the effect of the drug on the hypothalamo-pituitary adrenal system, we studied the cortisol response to 20 mg metoclopramide in patients with acromegaly, prolactinomas, and functional hyperprolactinemia and compared the results with the responses to insulin-induced hypoglycemia. In some patients, the effects of metoclopramide on CRH-induced ACTH and cortisol increase were studied to determine whether a change in dopaminergic (catecholaminergic) activity altered CRH stimulation of pituitary-adrenal function. No cortisol response to 20 mg metoclopramide occurred in 13 tests on 8 of 9 patients with prolactinoma or acromegaly with hyperprolactinemia, whereas both acromegalic patients without hyperprolactinemia had a response. All of the patients had a normal cortisol response to insulin-induced hypoglycemia. Pretreatment with metoclopramide enhanced the CRH-induced cortisol increase from 30-120 min after CRH in normal men, but only at 15 and 30 min in 5 agromegalic patients. The results suggest that metoclopramide acts in the hypothalamus to release ACTH through a dopamine antagonist-mediated (catecholaminergic) mechanism, and that metoclopramide may act additively with CRH to stimulate ACTH secretion in normal men. The absence of a metoclopramide-induced cortisol response in patients with acromegaly or prolactinomas and the absence of a normal cortisol response to metoclopramide-CRH in acromegalic patients could be due to endogenous catecholamine deficiency in these patients.

Acromegaly↗
PubMed1987

Pharmacokinetic and pharmacodynamic studies of piretanide in rabbits. I. Effect of different hydrated conditions.

The pharmacokinetics and pharmacodynamics of piretanide in rabbits were investigated. After intravenous administration, the plasma concentrations and the urinary excretion rates of piretanide, as well as the pharmacologic effects, were measured under two different hydrated conditions. In one experiment, the amount of the body fluid which was lost during diuresis was replaced by infusing Ringer's solution at exactly the same rate with the urine flow rate (treatment I). In another experiment, no compensatory infusion was made (treatment II). There was no appreciable difference between treatment I and II, as far as the plasma concentrations and urinary excretion rate were concerned. In spite of the similarities in the pharmacokinetic properties, the pharmacologic effects of piretanide were influenced considerably by the hydrated conditions of the body. The diuretic effect expressed as the excretion rate of the sum of urinary sodium and potassium was plotted against the corresponding urinary excretion rate of unchanged piretanide. The shape of the each graph showed a similar sigmoid like curve; however, the curve in treatment I was significantly shifted to the right compared to that in treatment II. This fact indicated that the pharmacologic effect of piretanide seemed to be modified by the contents of water and electrolytes in the body. The plasma concentrations and urinary excretion of piretanide were reasonably described by a linear three compartment open model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗