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Biomedical subjects

S Kaneta

Publications and source records attributed to S Kaneta.

34 records · Page 2Linked to original sources
PubMed1993

Effects of H2-antihistamines in murine models of immediate hypersensitivity and chronic inflammation.

Effects of H2-antihistamines alone and in combination with H1-antihistamines on immediate hypersensitivity and chronic inflammation in mice and rats were investigated. The mouse PCA reaction was inhibited partially by a minimum effective dose of diphenhydramine and blocked completely when administered simultaneously with either famotidine, ranitidine or cimetidine. There was similar synergism between H1- and H2-antihistamines in inhibiting the PCA-like reaction in rat paw. Famotidine alone was able to inhibit those two reactions in a large oral dose of 100 mg/kg. A five-day course of therapy with H2-antihistamines alone or in combination with pyrilamine, suppressed effectively the chronic swelling induced in the hind paw of BUF rats. From these results, it is deduced that simultaneous blockage of both histamine H1- and H2-receptors may be necessary for sufficient inhibition of the microvascular permeability increase in some kinds of anaphylactic reactions, and that histamine, mainly interacting with H2-receptors, may take an important role for activation of a certain phase of chronic inflammation where bone destruction, blood capillary growth and mast cell degranulation involve.

Animals↗
PubMed1993

[Alcohol-related problems in mortality in middle-aged urban-dwelling men from cerebro-cardiovascular diseases].

A survey was performed of the life-styles and medical histories of men, who died of cerebro-cardiovascular diseases at ages between 40 and 64 years in Hirakata, Neyagawa, Moriguchi and Kadoma cities in Osaka prefecture. Data was available on 127 of 172 men who died in 1988. Of these, 28 had histories of alcohol-related problems. Analysis showed that the amount of alcohol consumed was associated with disease history and serious alcohol-related problems. 1) Histories of hypertension, cerebrovascular and liver disease were found more often in heavy drinkers with a daily alcohol intake exceeding the equivalent of 46 g pure ethanol compared to either moderate drinkers with a daily alcohol intake of less than 46 g or abstainers. 2) Of 28 subjects with alcohol-related problems, one had been treated at a specialized alcoholic-clinic, two had been admitted to psychiatric hospitals and one subject had consulted a physician at a mental health clinic of the public health center in his community. 3) Although 18 of the 28 subjects with alcohol-related problems had their own regular doctors, they did not appear to have received adequate care. 4) Subjects with alcohol-related problems had histories of cerebrovascular and liver diseases more often than those without alcohol-related problems. 5) Subjects with alcohol-related problems were confronted with unemployment, divorce and housing problems more often than those without alcohol-related problems. With the increasing amount of alcohol consumption in Japan, alcohol-related problems need more attention. There is an urgent need to establish community-based strategies for prevention of alcohol-related problems and to organize a network of multi-disciplinary support teams for those with problems such as alcoholics in urban communities.

Adult↗
PubMed1992

Comparison of KRN2391 with nicorandil and nifedipine on canine coronary blood flow: antagonism by glibenclamide.

The mode of action of KRN2391 [N-cyano-N'-(2-nitroxyethyl)-3- pyridinecarboximidamide monomethanesulfonate] in coronary circulation was examined in anesthetized dogs in comparison with those of nicorandil and nifedipine. Administration of KRN2391 (10 micrograms/kg i.v.), nicorandil (300 micrograms/kg i.v.), and nifedipine (3 micrograms/kg i.v.) caused an increase in coronary blood flow (CBF) and decreases in mean blood pressure (MBP) and in coronary vascular resistance (CVR). Heart rate (HR) was slightly and simultaneously increased by the drugs. Glibenclamide (5 mg/kg i.v.) blocked the changes of these parameters caused by KRN2391 and nicorandil, but not those caused by nifedipine. The present study suggests that the mechanism of action through ATP-sensitive K channels which are blocked by glibenclamide may contribute, at least in part, to the effects of KRN2391 and nicorandil on CBF and blood pressure (BP).

Animals↗
PubMed1986

Mouse IgE-mediated paw anaphylaxis in mice and rats.

Anaphylactic swelling is induced in the hind paws of mice and rats by intravenous challenge of antigen 72 h after subplantar injection of mouse IgE-rich antiserum into the paws, and can be quantified rapidly and accurately by measuring paw thickness. The edema model described may serve as an alternative to passive cutaneous anaphylaxis for studying immediate allergic reactions with mouse homocytotropic antibodies and screening potential antiallergic drugs.

Animals↗
PubMed1984

Mouse paw anaphylaxis.

Anaphylactic swelling passively transferred to the hind paws of mice with homologous antibodies was investigated. The ascites fluid containing homocytotropic antibodies of the IgG1 class in a high concentration was obtained by repeated injections of bovine serum albumin in complete Freund's adjuvant into the peritoneal cavity of female ICR mice. The standard procedure for mouse paw anaphylaxis defined was as follows: female ICR mice received subcutaneously 25 microliters of a 1:20 diluted ascites in the hind footpad and 2 h later were given intravenously 1.0 mg of the antigen in saline, and subsequently at 5 min intervals paw thickness was assessed by means of a simple thickness gauge. Maximal paw edema occurred invariably 15 min after antigen challenge. Sex difference in response was not observed. Heating at 56 degrees C for 4 h resulted in a reduction of the activity of mouse ascites by approximately 40%. Histological examinations revealed that paw anaphylaxis was accompanied by mast cell degranulation and release of biologically active constituents from mast cell granules. Promethazine, pyrilamine, diphenhydramine, methysergide, cyproheptadine, ketotifen and phenoxybenzamine provided significant protection from the anaphylactic reaction in mice, while bromocriptine, dexamethasone and indomethacin were inactive. Relative drug effectiveness in paw anaphylaxis, passive cutaneous anaphylaxis and active and passive systemic anaphylaxis in mice was compared and discussed. Consequently, it was shown that mouse paw anaphylaxis was not only convenient for quantitative assessment of homocytotropic antibodies, but also useful in the routine work for screening of potential anti-allergic drugs.

Animals↗
PubMed1984

Progressive foot swelling in BUF rats. A new animal model for screening of anti-inflammatory and anti-rheumatic drugs.

Buffalo rats of a low adjuvant-arthritis responder strain demonstrate a continually increasing swelling in the hind foot inoculated with mycobacterial adjuvant, characterized by extensive panostitis, new bone formation and long-delayed bony calcification. A rapid regression of foot swelling was produced by a three-day course of therapy with indomethacin (1 mg/kg) or with dexamethasone (0.1 mg/kg), but a definite rebound was followed soon after termination of the therapy. This recurrent episode occurred repeatedly in the second and third therapeutic trials with the anti-inflammatory drugs in the same animals. The 5 days treatment with either levamisole (5 mg/kg) or cyclophosphamide (5 mg/kg) prevented further increase in the swelling for a long time period after withdrawal of the drug, and enhanced bone mineralization.

Animals↗
PubMed1983

Reduced drug metabolism in isolated hepatocytes from adjuvant arthritic rats.

Viable hepatocytes were isolated from the livers of rats with adjuvant arthritis by the collagenase-perfusion method and measured for activities of drug-metabolizing enzymes. These cells produced radioactive metabolites from 14C-aminopyrine and 14C-aniline to a much lesser extent than the control hepatocytes that were derived from pair-fed normal rats. On the other hand, 14C-aminopyrine was scarcely metabolized by non-parenchymal cells other than hepatocytes, even when incubated with those from control rats. Although there were no significant differences in cell yield, viability and oxygen consumption, the cellular uptake of indocyanine green was significantly slower in the arthritic hepatocytes than the control hepatocytes. Morphologically, the freshly isolated arthritic hepatocytes demonstrated the disappearance of the microvilli, the appearance of bleb-like protrusions in the plasma membrane and the widespread distribution of the rough endoplasmic reticulum associated with a relatively decreased area of the smooth endoplasmic reticulum in the cytoplasma. Biochemically, these cells showed a significantly higher RNA/DNA ratio and an ability to incorporate 14C-leucine into proteins more rapidly, as compared to the control hepatocytes. A possible relationship between the reduction of the drug metabolizing activity and the production of the acute phase proteins in rat hepatocytes after an inflammatory stimulus was discussed.

Aminopyrine↗
PubMed1979

Intraperitoneal systemic anaphylaxis in the mouse. I. Age-dependence of fatal anaphylactic shock.

Following the i.p. challenge of a shocking dose of BSA from 9 days up to 133 days after the s.c. injection of BSA in CFA, fatal anaphylaxis was induced regularly in female ICR mice that had been given the immunizing antigen when 8 weeks old. These immunized mice provided an antiserum to BSA that had the capacity to transfer fatal shock to normal recipient mice at a minimum Ab-N dose of 8 microgram when the i.p. route for challenge was employed. The optimal dose-range of antigen and antibody in order to elicit fatal shock following the i.p. challenge was much broader than that obtained by i.v. injection. Age is critical in producing fatal shock in mice; a 100% fatal anaphylaxis never occurred in groups of 6- and 7-week-old recipient mice although those at 8 weeks and older were sufficiently sensitized by the amounts of antibody given.

Aging↗
PubMedDate not supplied

Tolerance to the increase in coronary blood flow induced by KRN2391.

We examined whether KRN2391, isosorbide dinitrate and nitroglycerin induced tolerance in coronary arteries. Intracoronary arterial administration of KRN2391 (1 microgram), isosorbide dinitrate (30 micrograms) or nitroglycerin (3 micrograms) produced equipotent coronary vasodilatation. Development of tolerance was determined by whether the increase in coronary blood flow, caused by intracoronary arterial administration of these drugs, was attenuated by intravenous infusion of KRN2391, isosorbide dinitrate or nitroglycerin. The increase in coronary blood flow, caused by intracoronary arterial administration of KRN2391 was not affected by intravenous infusion of KRN2391 (0.3 or 1 micrograms/kg/min), isosorbide dinitrate (30 or 100 micrograms/kg/min) or nitroglycerin (1 or 3 micrograms/kg/min). The increase in coronary blood flow, caused by intracoronary arterial administration of isosorbide dinitrate or nitroglycerin, was significantly diminished by intravenous infusion of isosorbide dinitrate and nitroglycerin, but was unaffected by intravenous infusion of KRN2391. The present results suggest that KRN2391 does not induce acute tolerance by itself or cross-tolerance between KRN2391 and other nitrates.

Animals↗
PubMedDate not supplied

Comparative cardiovascular effects of KRN2391 and other coronary vasodilators in anesthetized open-chest dogs.

The effect of KRN2391 [N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate] on the cardiovascular system and on myocardial oxygen consumption was compared with that of nicorandil and nifedipine in anesthetized dogs. Intravenous administration of KRN2391 (3-30 micrograms/kg) and nifedipine (1 and 3 micrograms/kg) decreased mean aortic blood pressure and total peripheral vascular resistance, and increased coronary blood flow, cardiac output and stroke volume. Heart rate was not significantly affected by KRN2391, but slightly increased by 1 microgram/kg of nifedipine. Nicorandil (100 and 300 micrograms/kg, intravenously) decreased mean aortic blood pressure, cardiac output, stroke volume and total peripheral vascular resistance, but did not affect heart rate. Nicorandil also showed a tendency to decrease coronary blood flow after an initial increase. All drugs tested decreased the difference in oxygen concentration between arterial and coronary sinus blood, indicating that these drugs increased the oxygen supply to the heart. Myocardial oxygen consumption was significantly decreased by more than 10 micrograms/kg of KRN2391, but was not affected by nifedipine. Nicorandil showed a tendency to decrease the myocardial oxygen consumption, though not significantly. Thus, KRN2391 may be useful to treat ischemic heart disease, because it increases the coronary blood flow and the oxygen supply to the heart, and decreases the afterload and the myocardial oxygen consumption.

Anesthesia↗
PubMedDate not supplied

Cardiovascular effects of KRN2391 in anesthetized dogs: a comparison with cromakalim and nitroglycerin.

The cardiovascular effects of KRN2391, N-cyano-N'-(2-nitroxyethyl)-3-pyridine carboximidamide monomethanesulfonate, were compared with those of cromakalim and nitroglycerin in anesthetized dogs. KRN2391 (3-30 micrograms/kg, i.v.), cromakalim (3-30 micrograms/kg, i.v.) and nitroglycerin (1-10 micrograms/kg, i.v.) produced a dose-related decrease of the mean blood pressure with concomitant increase in heart rate. The increase in heart rate caused by cromakalim was lower than that caused by KRN2391 and nitroglycerin. Left ventricular end-diastolic pressure was decreased by all doses of KRN2391 and nitroglycerin. Cromakalim at 3 and 10 micrograms/kg decreased this end-diastolic pressure but increased it at 30 micrograms/kg. Left ventricular dP/dt was increased by KRN2391 and nitroglycerin but was decreased by cromakalim. KRN2391 and cromakalim produced a dose-dependent increase in aortic and coronary blood flow. Nitroglycerin showed biphasic changes in aortic and coronary blood flow, i.e., an initial increase followed by a decrease. At equipotent hypotensive doses, the increase in coronary blood flow induced by KRN2391 was greater than that by cromakalim and nitroglycerin, and total peripheral and coronary vascular resistances were decreased by KRN2391 and cromakalim. Nitroglycerin showed biphasic changes in total peripheral and coronary vascular resistances, i.e., these resistance showed an initial decrease followed by an increase. The relative decrease of coronary vascular resistance compared to the total peripheral vascular resistance was greater for KRN2391 than for cromakalim and nitroglycerin. The changes in hemodynamic parameters caused by KRN2391 were inhibited by pretreatment with glibenclamide (5 mg/kg, i.v.). These results suggest that the hemodynamic profile of KRN2391 is closer to that of cromakalim than to that of nitroglycerin, but that the selectivity for the coronary vascular bed is higher for KRN2391 than for cromakalim. In addition, it is considered that, compared with KRN2391 and nitroglycerin, cromakalim has a low selectivity for the vasculature vs the myocardium.

Anesthesia↗
PubMedDate not supplied

Comparison of coronary dilating effects of Ki1769, a new K channel opener of the pyridinecarboximidamide type, and nifedipine in anesthetized dogs.

The coronary dilating effect of a new type of K channel opener, N-cyano-N'-(2-phenethyl)-3-pyridinecarboximidamide (Ki1769), was examined in anesthetized dogs in comparison with that of nifedipine. Administration of Ki1769 (30 and 100 micrograms/kg, i.v.) and nifedipine (1 and 3 micrograms/kg, i.v.) produced a dose-dependent decrease of mean blood pressure with a concomitant increase in heart rate. Ki1769 and nifedipine dose-dependently increased coronary blood flow and aortic blood flow and decreased coronary vascular resistance and total peripheral vascular resistance. The percentage decrease of coronary vascular resistance was greater than that of total peripheral vascular resistance with Ki1769 and nifedipine, but Ki1769 showed a greater specificity in the decrease of coronary vascular resistance than nifedipine. Glibenclamide (5 mg/kg, i.v.) inhibited these hemodynamic effects of Ki1769 but did not affect those of nifedipine. These results suggest that the preferential effect of Ki1769 on the coronary vascular bed is greater than that of nifedipine. Such a profile of Ki1769 is based on its K channel-opening action.

Anesthesia↗
PubMedDate not supplied

No development of tolerance to the hypotensive effect of KRN2391, a novel vasodilator containing a nitrate moiety.

The present studies were performed to examine whether tolerance develops to the hypotensive effects of KRN2391, N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate. Rats were administered KRN2391 (0.3 or 1 mg/kg, s.c.) or nitroglycerin (10 mg/kg, s.c.) three times a day for 1 to 8 days and blood pressure was then measured under anesthesia. Chronic pretreatment with nitroglycerin attenuated the decrease in blood pressure induced by i.v. nitroglycerin but not that by i.v. KRN2391. Chronic pretreatment with KRN2391 (0.3 or 1 mg/kg, s.c.) had no effect on the decreases in blood pressure induced by i.v. nitroglycerin or i.v. KRN2391. It can be concluded that, in this rat model, no tolerance develops to the hypotensive effects of KRN2391.

Animals↗
PubMedDate not supplied

Comparison of the anti-vasoconstrictor effects of a novel vasodilator KRN2391, nicorandil and nifedipine on isolated porcine large coronary artery.

The anti-vasoconstrictor profile of KRN2391, a novel vasodilator, was compared with that of nicorandil and nifedipine in isolated porcine large coronary arteries contracted by KCl, noradrenaline, serotonin, acetylcholine, endothelin-1 and U46619, a thromboxane A2 analogue. KRN2391 (10(-8) - 3 x 10(-5) M), nicorandil (10(-7) - 3 x 10(-4) M) and nifedipine (10(-10) - 10(-5) M) inhibited these contractile responses in a concentration-dependent manner. KRN2391 and nicorandil completely abolished these contractile responses at their maximum effects. However, nifedipine caused less inhibition than KRN2391 and nicorandil and did not completely abolish the contractile responses. The relaxant activity of KRN2391 was more potent than that of nicorandil. This study shows that the anti-vasoconstrictor profiles of KRN2391, nicorandil and nifedipine involve different relaxant mechanisms.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗