[Study on prevention of infections in a diabetic patient with advanced cognition disorder].
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Aged↗
Biomedical subjects
M Nakashima
Publications and source records attributed to M Nakashima.
Effects of the ventricular premature beat on the alternation of the repolarization phase in ischemic myocardium during acute coronary occlusion in dogs.
Effects of ventricular premature beats (VPB) on the alternans of the ST segment (ST alternans, STA) in the epicardial ECG and of the monophasic action potential (MAP) were examined during acute coronary occlusion in dogs. When STA was recorded simultaneously from four different points it was discordant in most cases. The discordant STA was accompanied by discordant alternation of the repolarization phase of MAP. A VPB transformed the discordant alternans into a concordant one and potentiated the degree of alternans. Transient prolongation or shortening of the cycle length showed effects similar to those of the VPB. The concordant alternans which was transformed from a discordant one by a VPB was not remarkably potentiated by a VPB, or by prolongation or shortening of the cycle length. It is possible that the transformation of the discordant alternans into a concordant one may contribute to the potentiation of STA by a VPB, and that the effects of VPB are due to the effects of the compensatory pause as well as the short cycle length associated with the VPB.
Animals↗
Potentiating effects of a ventricular premature beat on the alternation of the ST-T complex of epicardial electrograms and the incidence of ventricular arrhythmias during acute coronary occlusion in dogs.
A relation between ST-T alternans (STTA) and incidence of ventricular arrhythmias (VA) was examined, and the effects of a premature beat on these were tested during acute coronary occlusion in dogs. Epicardial unipolar electrograms, epicardial and endocardial bipolar electrograms and monophasic action potentials were recorded during coronary occlusion. During the period of STTA, a remarkably late conduction and its alternation were also observed in ischemic areas. The more serious delay appeared during the negative deflection of the ST-T complex. VA followed mainly the negative deflection of the ST-T complex. The first premature activation appeared in either ischemic areas or the border areas. A ventricular premature beat (VPB) which occurred spontaneously or was produced by an electrical stimulation potentiated STTA, and additional VA frequently followed the negative deflection of the ST-T complex of the second sinus beat after the VPB. A VPB pronounced the conduction delay during the second sinus beat. The discordant STTA became concordant after the VPB. The duration of a monophasic action potential of the second sinus beat after the VPB in mildly ischemic areas decreased. These changes and enhanced STTA may contribute to the occurrence of the additional VA.
Animals↗
Amosulalol, a combined alpha and beta adrenoceptor antagonist: kinetics after intravenous and oral doses.
Amosulalol kinetic studies were conducted in seven subjects who received 0.16 mg/kg iv and in 18 subjects who received 12.5, 25, 50, 100, or 150 mg by mouth. Plasma levels of amosulalol after intravenous dosing declined biphasically and fitted a two-compartment model. Kinetics were as follows: coefficients A = 0.85 +/- 0.09 microgram/ml and B = 0.22 +/- 0.01 microgram/ml; rate constants alpha = 2.78 +/- 0.24 hr-1 and beta = 0.25 +/- 0.01 hr-1; elimination rate constants, k12 = 1.36 +/- 0.17 hr-1, k21 = 0.78 +/- 0.06 hr-1, and kel = 0.88 +/- 0.06 hr-1; terminal phase volume of distribution = 0.75 +/- 0.06 l/kg; clearance = 8.09 +/- 0.54 l/hr; AUC = 1.22 +/- 0.09 microgram . hr/ml; and t1/2 alpha = 0.26 +/- 0.02 hr and t1/2 beta = 2.8 +/- 0.1 hr. After single oral doses, amosulalol peak plasma levels were generally reached within 2 to 4 hr. Maximum plasma concentrations and AUC increased in a dose-dependent manner, whereas t1/2 were about 5 hr (range 4.4 to 5.7 hr) at each dose. Systemic availability of amosulalol was about 100% as determined by the ratio of AUC after oral and intravenous dosing. These results suggest that amosulalol is well absorbed and is little affected by first-pass metabolism.
Administration, Oral↗
Effects of biofeedback training on tonic masticatory neck reflex: a case report.
Biofeedback training to reduce muscle tension lowered not only the spontaneous activity but also the tonic neck reflex in the jaw closing muscles. Tolperisone-HCl, which may inhibit the gamma system, inhibited the tonic masticatory neck reflex, but did not reduce the patient's spontaneous activity of the jaw closing muscles in this case. Biofeedback training may be considered to reduce the gamma as well as alpha motor systems.
Biofeedback, Psychology↗
Extrinsic innervation of the canine superior vena cava, pulmonary, portal and renal veins.
The responses of the superior vena cava, portal, pulmonary, and renal veins to electrical stimulation of sympathetic nerves were investigated in dog. The vascular response was measured by the method with an intravascular cuff. The contractile responses to neural stimuli were mediated mainly by adrenergic mechanism in the four veins and that of the portal vein was, in addition, mediated in part by cholinergic one. The latter mechanism was also found in some cases of the pulmonary vein. As for the superior vena cava and the left renal vein the right-side dominancy in innervation was observed. These observations suggest a possible correlation between the embryogenesis of vein and its innervation.
Animals↗
Effect of papaverine on organic anion transport in rat kidney cortical slices.
The present studies were conducted to further investigate a role of cyclic nucleotides for organic anion transport in rat kidney cortical slices by using papaverine as a phosphodiesterase inhibitor. Papaverine was chosen for this study because this drug is an organic cation, a transport system of which is thought to be clearly separable from an organic anion transport system. Papaverine inhibited not only p-aminohippuric acid (PAH) accumulation in the slices but also urate one. Pretreatment of the slices with papaverine was effective for significant inhibition of PAH accumulation during subsequent incubation in the absence of papaverine. The present results suggest that a relationship may exist between cyclic nucleotides and organic anion transport in rat kidney cortical slices, although further work is necessary before the above evaluation can be given.
Animals↗
The effect of racemomycin-D, a nephrotoxic antibiotic, on cellular metabolism of rat kidney cortex in vitro.
In vitro effects of racemomycin-D on cellular metabolism were examined in rat kidney. Racemomycin-D decreased the concentration gradient of Na+ and K+ across the cell membranes, but failed to influence water content and ATP concentration of kidney cortical slices. The antibiotic inhibited microsomal (Na+ + K+)-ATPase. Preincubation of the microsomes with racemomycin-D enhanced the inhibition about 1.8-fold. Succinoxidase activity of mitochondria remained unaltered in the presence of racemomycin-D, but the antibiotic potently decreased ATP-dependent Ca2+ and Mg2+ uptakes by mitochondria. These results suggest that racemomycin-D probably disorders intracellular homeostasis of Na+, K+ and Ca2+.
Adenosine Triphosphate↗
Changes in the effects of clonidine on left atrium and hindlimb vasculature of rats in various thyroid states. A study of the responsiveness of alpha 2-adrenoceptors in the cardiovascular system.
Postsynaptic alpha 2-adrenoceptors have been reported to exist in various tissues, including vascular smooth muscle. In order to investigate the possibility of their mediating a positive inotropic change and clarify the influence of the thyroid on their responsiveness, we examined the effects of clonidine, a known alpha 2-agonist, on the isolated left atria and femoral vascular beds of rats which were made hypo-, hyper- or euthyroid. Clonidine caused a dose-dependent positive inotropic change in the hypothyroid rat atrium, which was thought to be due to its alpha 1-stimulating action because of the antagonistic effect exerted by either phentolamine (10(-6) M) or prazosin (10(-7) M), but not by yohimbine (10(-7) M) or cimetidine (10(-5) M). In the hyperthyroid rat atrium, clonidine exerted a negative inotropic effect at high concentrations, which was thought to be due to its direct action on the cardiac muscle. Clonidine did not cause any inotropic change in the euthyroid rat atrium. Thus, an inotropic change mediated by the postsynaptic alpha 2-adrenoceptors could not be demonstrated in the rat heart. In the experiment involving hindlimb perfusion, clonidine caused vasoconstriction which was antagonized by yohimbine (10 micrograms/min). This effect was significantly augmented in the hypothyroid rats but not changed in the hyperthyroid ones. The vasoconstrictive effect of phenylephrine was found to be reduced in both hypo- and hyperthyroid rats. These results suggest that, in the peripheral vascular system, thyroid function also influences the postsynaptic alpha 2-adrenoceptors, but not in the same way as it affects the alpha 1-adrenoceptors.
Animals↗
Hemodynamic effects of arotinolol in anesthetized dogs and its affinities for adrenoceptors in vitro.
Hemodynamic actions of arotinolol in anesthetized dogs and its effects on alpha- and beta-adrenoceptors were examined. Arotinolol produced dose-dependent decrease in mean blood pressure, heart rate, cardiac output, maximum rate of left ventricular pressure rise and coronary blood flow in a dose range of 1 microgram/kg-3 mg/kg. Total peripheral resistance (TPR) increased with arotinolol dose-dependently in a dose range of 1 microgram/kg-0.3 mg/kg, but at doses of 1 and 3 mg/kg the increase in TPR was less. Arotinolol at a dose of 10 micrograms/kg significantly inhibited the blood pressure and heart rate responses to isoproterenol. Propranolol at the same dose produced only a slight inhibition of these. Arotinolol at a dose of 3 mg/kg attenuated the pressor response to phenylephrine without any effect on the response to angiotensin-II in anesthetized dogs. Propranolol at the same dose produced only a slight inhibition of the response to phenylephrine. In the study of radioactive ligand binding assays, arotinolol showed high affinities for both beta 1- and beta 2-adrenoceptors. Arotinolol showed an affinity also for alpha 1-adrenoceptors which was comparable to the affinity of yohimbine. Thus, the present results support the idea that arotinolol possesses both alpha- and beta-adrenoceptors blocking effects.
Adrenergic beta-Antagonists↗
Phase I study of 2,4-diamino-6-(2,5-dichlorophenyl)-s-triazine maleate (MN-1695), a new anti-ulcer agent.
A phase I study of 2,4-diamino-6-(2,5-dichlorophenyl)-s-triazine (MN-1695), which is expected to have an anti-ulcer effect, was performed in 14 healthy male subjects. The safety and pharmacokinetics were examined in single-dose oral administration of 1, 2, 4, 8 and 16 mg/body and multiple-dose administration of 2 mg/body/day, once daily, for 28 consecutive days. As for the subjective symptoms, only light headache, general malaise and heart burn were observed in two out of 4 subjects in the 16-mg group. No abnormalities were found in blood pressure, pulse rate, respiratory rate, body temperature, body weight and ECG both in single- and multiple-dose studies. No abnormal changes attributed to this drug appeared in hematological and biochemical examinations and urinalysis. Times for reaching the maximum plasma concentration in the single-dose study were 3.5, 8 and 3.3 h in 4-, 8- and 16-mg groups, respectively. The elimination half-lives from the plasma were 152, 145 and 148 h for the 3 groups, respectively. The plasma concentration curves in the multiple-dose study were similar to those simulated with the pharmacokinetic parameters obtained in the single-dose study. The plasma concentration increased until the 14th day, as the administration continued, and reached steady state thereafter; there seemed to be no abnormal cumulation. The elimination patterns after multiple-dose administration were almost the same as those in the single-dose study; the half-life was about 170 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Induction of opposite response of hindlimb vasculature to adrenergic agents in hypothyroid rats.
In order to investigate whether hypothyroidism induces some functional change in the vascular smooth muscle, the responsiveness of the femoral vascular bed of hypothyroid rats to vasoactive agents was compared with that of euthyroid rats. The vascular beds were perfused by using the constant flow method. Ad libitum feeding of 0.15% 6-propylthiouracil to young male Wistar rats (120 g) over 3 months leads to hypothyroidism. Hypothyroidism did not induce any changes in the Ach- or papaverine-induced vasodilation and 5-HT-induced vasoconstriction. In contrast to euthyroidism, hypothyroidism induces a marked augmentation of the clonidine-induced vasoconstriction, while the phenylephrine-induced vasoconstriction and isoprenaline-induced vasodilation were clearly attenuated. The response to phenylephrine in euthyroidism was predominantly inhibited by prazosin and was slightly modified by yohimbine. While the attenuated response to phenylephrine in hypothyroidism was modified by these blockers in a converse manner, the response to clonidine in each rat group was not modified by prazosin, but markedly inhibited by yohimbine. From these results the following conclusions were obtained: both alpha-1 and alpha-2 adrenoceptors in the femoral vascular beds of eu- and hypothyroid rats responded to phenylephrine; phenylephrine stimulated predominantly alpha-1 adrenoceptors in euthyroidism; hypothyroidism caused an attenuation of the responsiveness mediated through alpha-1 adrenoceptors and an augmentation of that of alpha-2 receptors; hypothyroidism caused an opposite response, mediated through alpha- and beta-receptors, without influencing muscarinic and serotoninergic responses; augmentation of the alpha-2 response and attenuation of alpha-1 and beta-2 responses caused by hypothyroidism may be attributed to functional changes at receptor sites.
Acetylcholine↗
Age-dependent differences in the positive inotropic effect of phenylephrine on rat isolated atria.
The age-dependent differences in the involvement of alpha-adrenoceptors in the positive inotropic effect of phenylephrine (Phe) were examined in isolated atria of male Wistar rats 6 weeks (6W), 10 weeks and 7 months (7M) of age. The maximal increase in tension development induced by Phe increased with age, whereas the EC50 values for the positive inotropic effect of Phe did not change with age. The inhibitory effect of phentolamine on the response to Phe increased with age. Propranolol caused only slight inhibition of the effect of Phe in both 6W and 7M rats, and the EC50 values for Phe in the presence of propranolol did not change significantly with age. The EC50 values for isoprenaline and 5-hydroxytryptamine in 7M rats were higher than those in 6W rats. In 7M rats, the duration of the tension development was only slightly affected by Phe in the presence or absence of propranolol, but it was markedly decreased by Phe in the presence of phentolamine. The dose-response curve for Phe was markedly shifted to the left by papaverine in 6W rats, but slightly in 7M rats. The dose-response curve for isoprenaline was markedly shifted to the left by papaverine in both groups. These results are consistent with effects of Phe being mediated by both alpha- and beta-adrenoceptors in both 6W and 7M rats, but there is a shift in the balance from rather more beta-receptors in the young animals to more alpha-receptors in the adults.
Age Factors↗
Effects of calcium antagonists on the electrical alternans of the ST segment and on associated mechanical alternans during acute coronary occlusion in dogs.
Effects of calcium antagonists on the ST alternans and associated mechanical alternans during acute coronary occlusion were examined in anesthetized dogs. The heart rate was fixed by atrial pacing. The intravenous administration of 0.2 mg/kg verapamil attenuated the ST alternans as did 0.5 mg/kg diltiazem. Although these drugs significantly attenuated TQ depression during occlusion, the attenuation was observed after a longer period of occlusion and when the degree of TQ depression was comparable to that during the control occlusion. Nifedipine, 0.03 mg/kg, slightly attenuated the ST alternans, but 0.5 mg/kg dipyridamole had no effect. These results support the idea that slow inward currents are involved in the ST alternans. On the other hand, the mechanical alternans was attenuated in six of 11 dogs. It is probable that factors other than the electrical alternans may also contribute to the mechanical alternans.
Acute Disease↗
Affinities for alpha- and beta-adrenoceptor subtypes of YM-09538, a new combined alpha- and beta-adrenoceptor antagonist, by radioligand binding assay.
The binding properties of YM-09538 and some known adrenoceptor agonists and antagonists to alpha- and beta-adrenoceptors were studied by radioligand binding assays using [3H]-prazosin, [3H]-clonidine and (-)-[3H]-dihydroalprenolol ([3H]-DHA). The relative order of potencies of YM-09538 and 5 alpha-adrenergic agents for inhibition of [3H]-prazosin binding to rat brain membranes was as follows: prazosin greater than YM-09538 = phentolamine greater than labetalol greater than yohimbine greater than clonidine. In contrast, the order of potencies of these agents for [3H]-clonidine sites was as follows: clonidine greater than phentolamine greater than yohimbine greater than prazosin greater than YM-09538 greater than labetalol. The rank order of potencies of YM-09538 and 4 beta-adrenergic agents in inhibiting the binding of [3H]-DHA to guinea-pig heart membranes was the same as that to guinea-pig lung membranes: pindolol greater than propranolol greater than labetalol greater than YM-09538 greater than atenolol. Based on Ki values, YM-09538 displayed a 1,380-fold alpha 1-selectivity at alpha-adrenoceptors and no selectivity at beta-adrenoceptors. The biochemical potencies of YM-09538 observed in the present study correlated well with its pharmacological potencies obtained from previously reported literature.
Adrenergic alpha-Antagonists↗
[Cefotiam passage into the maxillary sinus tissues].
Clinical study was made on cefotiam (CTM) and the following results were obtained. Tissue concentrations of CTM were determined 1 hour after intravenous injection (CTM 1 g) in chronic sinusitis and maxillary cyst. Concentrations of CTM were 16.53 micrograms/g, 13.26 micrograms/g in mucosa of the maxillary sinus, maxillary cyst, respectively. Antibacterial activity of CTM was measured on Escherichia coli, Staphylococcus epidermidis, Aerococcus, Acidaminococcus fermentans, Peptostreptococcus anaerobius; that were isolated from pus of maxillary sinus. The highest MIC on them was 3.13 micrograms/ml.
Adolescent↗
[Morphological study of monocrotaline-induced pulmonary hypertension in rats].
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Animals↗