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Biomedical subjects

M Iriki

Publications and source records attributed to M Iriki.

At least 37 records · Page 2Linked to original sources

Action site of circulating interleukin-1 on the rabbit brain.

Interleukin-1 (IL-1) is now generally accepted as an endogenous pyrogenic mediator of fever induction. IL-1 induces fever by means of activation of arachidonate metabolism in the brain. However, whether circulating IL-1 enters the brain or not, further, the question of where is the action site of circulating IL-1 on the brain, have not been clearly demonstrated. In the present study, to investigate the site of action of circulating IL-1 on the brain, recombinant rabbit interleukin-1 beta (IL-1 beta) was labeled with colloidal gold, injected into the carotid artery of anesthetized rabbits and traced in the brain tissue by means of electron microscopy. Dose-dependent increase in colonic temperature was induced by intravenous injection of used IL-1 in rabbits, while heated IL-1 beta lost the pyrogenicity. Injection of solution of colloidal gold per se did not affect the colonic temperature of afebrile conscious rabbits. However, the IL-1/gold conjugates induced fever; IL-1 beta retained its pyrogenic potency even after labeling with gold. By electron microscopy, the IL-1/gold conjugates were observed on the surface and in the vesicle of endothelial cells of the capillary in the region of the anteroventral third ventricle. This implies that circulating IL-1 acts, as the initial step to induce fever, on the endothelium in that region.

Animals↗

[Effect of propiverine hydrochloride on the function of the bladder in decerebrated dogs].

The effect of propiverine hydrochloride (P-4) on the function of the bladder in decerebrated dogs was compared with that of propantheline, an anticholinergic drug which is used for the treatment of micturitional disorders. P-4 (5 and 10 mg/kg, i.v.) significantly increased maximum vesical volume (Vmax); and at the dose of 10 mg/kg, i.v., it also significantly increased effective vesical volume (EV) when determined by cystometry. However, at the dose level of 2, 5 and 10 mg/kg, i.v., P-4 had no effect on residual volume (RV) after micturition contraction. Propantheline (0.25 and 0.5 mg/kg, i.v.) also significantly increased Vmax, but showed no effect on EV. At doses higher than 0.016 mg/kg, i.v., propantheline significantly increased RV. These findings indicate that P-4 is a useful drug for the treatment of pollakiuria.

Benzilates↗

[Effects of propiverine hydrochloride and its metabolites on isolated guinea pig urinary bladder].

The effects of P-4 and its active metabolites in human blood and urine and the effects of 1-methyl-4-piperidyl diphenylpropoxyacetate N-oxide [P-4(N----O)], 1-methyl-4-piperidyl benzilate N-oxide [DPr-P-4(N----O)] and 1-methyl-4-piperidyl benzilate (DPr-P-4) on isolated guinea pig urinary bladder were investigated. At doses of 10(-6) or 10(-5) M, P-4 shifted the dose-response curve for acetylcholine (ACh) to the right, and at a dose of 10(-5) M, it also inhibited the maximum response of ACh. At doses of 10(-5) M or more, P-4(N----O) inhibited the maximum response of ACh. DPr-P-4(N----O) or DPr-P-4 shifted the dose-response curve for ACh to the right at doses of 10(-6)-10(-4) M or at doses of 10(-7)-10(-5) M. P-4 at doses of 10(-6) M or more inhibited the KCl (100 mM)-induced contraction in a dose-dependent manner, and its potency was quite equal to that of terodiline. The inhibitory effect of P-4(N----O), DPr-P-4(N----O) and DPr-P-4 in the KCl (100 mM)-induced contraction were weaker than that of P-4. P-4 and P-4(N----O) had a dose-dependent inhibitory effect on K+-induced 45Ca influx in isolated guinea-pig urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

[Effects of propiverine hydrochloride (P-4) and its metabolites on urinary bladder function in anesthetized rats].

The effects of P-4 and its active metabolites, 1-methyl-4-piperidyl diphenylpropoxyacetate N-oxide[P-4(N----O)], 1-methyl-4-piperidyl benzilate N-oxide [DPr-P-4 (N----O)] and 1-methyl-4-piperidyl benzilate hydrochloride (DPr-P-4), on urinary bladder function were investigated in urethane anesthetized rats. By cystometrography, P-4 (2, 4 mg/kg, i.v.) and P-4 (N----O) (4 mg/kg, i.v.), which have direct action on smooth muscles, significantly increased the maximum vesical volume. As for rhythmic bladder contractions, P-4 (1,2,4 mg/kg, i.v.) and P-4 (N----O) (2, 4 mg/kg, i.v.) significantly decreased the frequency with a slight decrease in the amplitude. On the other hand, DPr-P-4 (N----O) (0.1, 0.5 mg/kg, i.v.) and DPr-P-4 (0.01, 0.05 mg/kg, i.v.), which have anticholinergic effects, significantly inhibited the maximum vesical pressure on the cystometrograms, and DPr-P-4 (N----O) (0.1, 0.5 mg/kg, i.v.) and DPr-P-4 (0.005, 0.05 mg/kg, i.v.) significantly inhibited the amplitude of the rhythmic bladder contractions. The effects of flavoxate and papaverine were similar to those of P-4 and P-4 (N----O), but the effects of propantheline and atropine were similar to those of DPr-P-4 (N----O) and DPr-P-4 in these two experimental methods. These results suggest that the clinical effects of P-4 are based not only on the actions of P-4 itself but also on those of its active metabolites.

Animals↗

[Effect of propiverine hydrochloride on the function of the bladder in dogs].

Propiverine hydrochloride (P-4) is a new derivative of benzilic acid. The effect of P-4 on the function of the bladder in anesthetized dogs was studied in comparison with flavoxate, which is clinically used for the treatment of pollakiuria. P-4 (4 mg/kg, i.v.) caused a significant increase in maximum vesical volume (Vmax), which was estimated by a cystometrogram. A similar effect was also observed following intravenous administration of verapamil (1 mg/kg), while flavoxate (4 mg/kg, i.v.) caused no significant changes in Vmax. P-4 significantly decreased the frequency of rhythmic bladder contractions at doses higher than 1 mg/kg, i.v., whereas flavoxate first revealed a significant decrease at 4 mg/kg, i.v. Thus the inhibitory effect of P-4 on the micturition movements of the bladder is more potent than that of flavoxate. These findings indicate that P-4 is a useful drug for the treatment of pollakiuria.

Animals↗

Regional differentiation of sympathetic nerve activity during fever caused by intracerebroventricular injection of PGE2.

In urethane-anesthetized rabbits prostaglandin E2 (PGE2) injected into a lateral cerebral ventricle (icv) produced hyperthermia. During the phase of rising rectal temperature, renal sympathetic activity monitored by multi-unit recording was reduced while the drop of ear skin temperature indicated cutaneous sympathetic activation. These reciprocal changes in activity corresponded to those typical for cold stress as well as for the phase of rising body temperature in fever induced by endotoxic lipopolysaccharides (LPS). However, a slight early stimulation of the heart rate after icv PGE2, contrasted to the initial reductions seen with LPS fever and in the cold. After sino-aortic denervation renal sympathetic inhibition in response to icv PGE2 was reduced but not abolished. After cervical vagotomy the antagonism between cutaneous and visceral sympathetic activity and the increase in heart rate became more prominent. During the phase of subsiding hyperthermia after icv PGE2, renal sympathetic activity returned to its control level, but, unlike LPS fever, did not exceed it. The results of this study indicate that the reciprocal changes in cutaneous and renal sympathetic activity, but not of sympathetic outflow to the heart, are identical during the phase of rising temperature in PGE2 and LPS fever. During the phase of subsiding hyperthermia, renal sympathetic activities change to different extents in PGE2 and LPS fever.

Animals↗

Effect of indomethacin on febrile response to recombinant human interleukin 1-alpha in rabbits.

Effects of indomethacin, a potent inhibitor of prostaglandin (PG) synthesis, on the fever induced by recombinant human interleukin 1-alpha (rhIL 1-alpha) was studied in conscious rabbits. Intracerebroventricularly administered rhIL 1-alpha induced a dose-dependent increase in colonic temperature that was prominently suppressed by pretreatment with indomethacin given either intracerebroventricularly or subcutaneously. On the other hand, fever induced by intravenous administration of rhIL 1-alpha was not completely suppressed by either subcutaneous or intracerebroventricular indomethacin; a small rise in colonic temperature persisted at approximately 45 min after rhIL 1-alpha injection. This rise in colonic temperature was suppressed when indomethacin was given both intracerebroventricularly and subcutaneously. It is suggested that PGs synthesized in the central nervous system contribute to the IL 1 fever and that part of IL 1-alpha given peripherally is also transmitted into the central nervous system to contribute to IL 1 fever.

Animals↗

Fever and fever syndrome--current problems.

Research into the complex humoral and neurophysiological events of pyrogen-induced fever has proceeded rapidly to establish the thermal and non-thermal components of the fever syndrome. The major breakthroughs derive from the elucidation of the identity of the endogenous pyrogen interleukin 1 with the humoral factors responsible for the acute phase reaction and for the activation of lymphocytic, cellular, and immunological defence as host responses to infections. As a consequence, fever research is no longer concerned primarily with the changes in temperature regulation responsible for the febrile alteration of temperature regulation, but aims at the elucidation of the contributions that are made by both the thermal and non-thermal components of the fever syndrome to the defence of the host against the microbial intruder responsible for this syndrome. In order to account for this development in these introductory remarks to the current issues of fever research, this review has tried to pay particular attention to the following points: 1) The role of humoral factors in the generation of febrile hyperthermia, including endogenous pyrogens as well as mediators acting on the thermoregulatory center. 2) The "fever syndrome" with special consideration of its regulation and of the significance of its components from the viewpoint of fever as a host-defence reaction. 3) The assessment of the role of PG's in the generation of the fever syndrome, both as putative central mediators and as systemically released agents, with special consideration of the inhibitory action of the established antipyretic drugs on PG synthesis.

Antibody Formation↗

Threshold dissociation of thermoregulatory effector responses in febrile rabbits.

When the core temperature stabilizes at a hyperthermic level after iv injection of lipopolysaccharide (LPS), the threshold core temperature for cutaneous vasoconstriction (Thcv) is significantly increased in hot and neutral environments, while the threshold core temperature for shivering (Thsh) is not significantly altered in hot or cold environments but is significantly reduced at thermoneutrality. This type of dissociated threshold alterations of thermoregulatory effector responses seems to be typical for the febrile response of rabbits to LPS. Because the same threshold dissociation can be demonstrated after icv injection of LPS, the systemic and the central effects of LPS in the generation of fever seem to be mediated by identical mechanisms. Prostaglandins of the E series (PGE), one of the mediators considered as important in fever generation, cause parallel increases in Thcv and Thsh when injected icv. This indicates that the mode of action of PGE on the central targets producing hyperthermia differs from that of the ensemble of mediators involved in the generation of LPS fever in rabbits. In rabbits pretreated with aspirin, the threshold dissociation after iv LPS injection still occurs. This indicates that factors other than PGE play an important role in the generation of the threshold dissociation of thermoregulatory effector responses, which is typical for LPS fever. These data indicate also that the states of activity of the thermoregulatory effectors involved in the febrile responses can be altered individually and that the activities of these effectors during LPS fever are quite different from their activities in the control state.

Animals↗

Hypothermia enhances acetylcholine-induced contraction of isolated rat ileum.

The amplitude of acetylcholine (ACh)-induced contraction of isolated rat ileum was enhanced at medium temperatures lower than normal body temperature. Maximum enhancement was achieved between 30 and 25 degrees C. Changes in medium pH and activities of the enteric nervous system due to temperature changes were not essential for this enhancement.

Acetylcholine↗

Characteristics of cardiovascular responses of the bullfrog (Rana catesbeiana) to thermal stimulation of the spinal cord.

Selective thermal stimulation of the spinal cord caused changes in ventricular pressure (VP) and blood flow of the pulmocutaneous artery (PCBF) in the bullfrog, Rana catesbeiana, anaesthetized with urethane. Warming the spinal cord significantly increased VP from 28.4 +/- 2.5 to 37.2 +/- 3.5 mmHg (n = 8) and PCBF from 24.5 +/- 1.4 to 29.5 +/- 2.0 ml/min (n = 5). Spinal cord cooling significantly decreased VP from 29.3 +/- 2.5 to 24.0 +/- 1.9 mmHg (n = 6) and PCBF from 22.4 +/- 1.4 to 18.5 +/- 1.7 ml/min (n = 5). Although heart rate did not exhibit significant changes during thermal stimulation, changes in cardiac output were achieved by changes in VP, i.e. changes in stroke volume. Changes in VP were antagonized with propranolol, but not influenced by lower sympathectomy which eliminates the catecholamine release for the chromaffin tissue. Atropine significantly increased resting PCBF but failed to antagonize changes in PCBF. This shows that changes in PCBF during spinal cord thermal stimulation are not mediated by an active vasomotor mechanism, but result from changes in cardiac output. The present results show that changes in spinal cord temperature induce inotropic effects on the bullfrog heart through a beta-adrenergic mechanism of sympathetic nervous origin.

Animals↗

Comparison of the action of prostaglandin with endotoxin on thermoregulatory response thresholds.

Prostaglandin E2 (PGE2) and lipopolysaccharide (LPS) derived from E. coli were injected into the lateral cerebral ventricle of rabbits at 30 degrees C ambient temperature. The threshold core temperatures for ear cutaneous vasoconstriction (Thv) and shivering (Thsh) were determined by whole-body cooling with an intestinal thermode. Each threshold, as determined at the plateau phase of LPS fever and PGE2 hyperthermia respectively, were compared with the control values before LPS and PGE2 injection. Thsh was not changed by the injection of LPS, while Thv was increased. After PGE2 injection both Thsh and Thv were increased in comparison to their control levels. These changes paralleled the elevation of core temperature. The present study does not exclude prostaglandins as humoral mediators involved in some of the central processes generating fever, but suggest at the same time that there are additional properties of LPS fever for which prostaglandins do not account.

Animals↗

Cardiovascular responses of the bullfrog (Rana catesbeiana) to thermal stimulation of the spinal cord.

Selective thermal stimulation of the spinal cord was performed in the bullfrog (Rana catesbeiana). Spinal cord warming caused an increase in systolic pressure of the truncus arteriosus, and cooling caused a decrease. Spinal cord warming caused an increase in systolic and pulse pressures of the conus arteriosus, and cooling caused a decrease. These results showed the temperature perceptibility of the spinal cord and a relationship between spinal cord temperature and autonomic functions in the frog as in other endothermic and ectothermic species.

Animals↗