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Biomedical subjects

K Ohmori

Publications and source records attributed to K Ohmori.

At least 55 records · Page 3Linked to original sources
PubMed2001

Pioglitazone improves left ventricular diastolic function and decreases collagen accumulation in prediabetic stage of a type II diabetic rat.

This study investigated the effect of pioglitazone, an insulin sensitizer, on metabolic abnormalities and oxidative stress as a cause of myocardial collagen accumulation in prediabetic rat hearts. Twenty male diabetic rats and 9 male nondiabetic age-matched rats were used. The diabetic rats were divided into two groups: diabetic treated and untreated. Pioglitazone was mixed in rat chow fed to the diabetic treated group (0.01%). Treatment duration was 5 weeks. At baseline (15 weeks) and 20 weeks of age, blood glucose, lipid, insulin, and plasma malondialdehyde-thiobarbituric acid (MDA) levels were measured and Doppler echocardiography was tracked. At 20 weeks of age, left ventricular collagen content was studied. Blood glucose, plasma insulin, and triglyceride levels in the diabetic treated group were significantly lower than those in the untreated diabetic group. Deceleration time (ms) of early diastolic inflow in the treated diabetic group decreased significantly compared with the untreated diabetic group (65 +/- 8 vs. 77 +/- 8, p < 0.01). Ratio of left ventricular weight to body weight (mg/g) and ratio of left ventricular collagen content to dry weight (mg/100 mg) were decreased in the treated diabetic group (1.5 +/- 0.1, 1.3 +/- 0.3) compared with the untreated diabetic group (1.7 +/- 0.2, p < 0.01; 1.7 +/- 0.3, p < 0.05). Plasma MDA concentration (nmol/ml) significantly decreased (2.9 +/- 0.3 at baseline to 2.3 +/- 0.3 at 20 weeks, p = 0.001) in the treated diabetic group, and was lower than that in the untreated diabetic group (3.2 +/- 0.7 at 20 weeks, p < 0.05). Pioglitazone improved glucose and lipid metabolism and reduced oxidative stress in the left ventricle, which decreased left ventricular collagen accumulation and improved left ventricular diastolic function of prediabetic rat hearts.

Animals↗
PubMed2001

Effects of diacerein on indomethacin-induced gastric ulceration.

We investigated the effect of diacerein, an antiosteoarthritic agent, and its metabolite, rhein, on the production of reactive oxygen species (ROS) from neutrophils as well as the protective effect of diacerein on indomethacin-induced gastric ulceration and its protection mechanism. Rhein inhibited the ROS production from N-formyl-methionyl-leucyl-phenylalanine or phorbol-12-myristate-13-acetate-activated human peripheral neutrophils. Indomethacin-induced gastric ulceration was significantly inhibited by oxygen radical scavengers and 16,16-dimethyl-prostaglandin E(2) (dmPGE(2)) but not by allopurinol. Diacerein inhibited indomethacin-induced gastric ulceration in a dose-dependent manner. Diacerein did not affect the gastric mucosal PGE(2) content. In addition, diacerein inhibited HCl + ethanol-induced gastric ulceration. These data indicate that the inhibitory effect of diacerein on indomethacin-induced gastric ulceration could be mediated not by the augmentation of gastric mucosal PGE(2) production but by the suppression of ROS production based on its inhibition of neutrophil activation.

Animals↗
PubMed2001

A multi-element carotid tonometry sensor for non-invasive measurement of pulse wave velocity.

A new pulse wave velocity (PWV) measurement system has been developed using a novel multi-element tonometry carotid sensor combined with a heart sound sensor. In this system, PWV is derived from the time lag between the second heart sound (S2) obtained from the heart sound sensor and the dicrotic notch in the carotid pulse waveform, and the physical distance between the heart and the neck. We assessed the accuracy of the system in an animal model. The study was divided into two groups: in Group I the tonometric sensor was directly applied to the exposed artery, while in Group II the sensor was applied over the skin and subcutaneous tissues covering the artery. To examine the fidelity of the dicrotic notch, the ejection time with the tonometry sensor was compared with that obtained from the intra-arterial catheter measurement. The correlation coefficients between them were 0.99 in both groups. The bias error (defined as the mean of the differences between the tonometry and the catheter measurements) +/-2SD was 0.13+/-1.45 ms in Group I and 0.16+/-1.64 ms in Group II. These results confirmed that the arterial wall, subcutaneous tissue and skin did not affect the accuracy of the dicrotic notch fidelity. The reproducibility of the system was assessed in 18 human subjects. The 2SD of intraobserver and interobserver reproducibility of the S2-carotid PWV measurement were 0.54 and 0.38 m/s, respectively, demonstrating high reproducibility of the measurement. From a clinical point of view, the S2-carotid PWV was compared with the aortic PWV. The bias error +/-2SD between the two measurements was -0.14+/-3.24 m/s with the correlation coefficient being 0.73. Although the S2-carotid PWV may not replace the aortic PWV directly, we believe that the S2-carotid PWV with the new system may become a new clinical parameter for early detection of cardiovascular disorders such as cerebrovascular diseases.

Adult↗
PubMed2001

Improvement of left ventricular diastolic dynamics in prediabetic stage of a type II diabetic rat model after troglitazone treatment.

Troglitazone, an oral antidiabetic agent, has hypoglycemic effects in insulin-resistant animal models and humans. This study was conducted to evaluate its effect on left ventricular diastolic dynamics of a spontaneous diabetic (DM) rat model. Twenty DM rats and 20 age-matched nonDM rats were used, and 10 of each group were treated with troglitazone as a 0.2% food admixture for 10 weeks. At 5 and 15 weeks of age, Doppler echocardiography and M-mode echocardiography were performed. Troglitazone treatment significantly improved the left ventricular diastolic dynamics of DM rats: deceleration time (msec) of early diastolic inflow decreased significantly (treated 52 +/- 3 vs untreated 64 +/- 5, p = 0.0002), and peak velocity of early transmitral inflow (cm/sec) increased significantly (treated 96 +/- 7 vs untreated 86 +/- 8, p = 0.0216). The data suggest that troglitazone improves left ventricular diastolic dynamics of a DM rat model at prediabetic stage.

Animals↗
PubMed2001

Suppression of fatty acid metabolism after exercise stress in patients with no electrocardiographic ST segment shift during balloon angioplasty.

Although ST segment shift is a marker of myocardial ischemia, some patients have no ST segment shift during percutaneous transluminal coronary angioplasty (PTCA). The aim of this study is to investigate myocardial perfusion and metabolism in adaptation for ischemia using 201TI and 123I-BMIPP dual exercise stress myocardial single photon emission computed tomography (SPECT) (dual stress SPECT). In 28 patients with coronary artery disease, dual stress SPECT was performed 3 weeks before PTCA. Early and delayed images were obtained at 5 minutes and at 3 hours after termination of ergometer stress, respectively. During PTCA, 12-lead ECG was recorded, and a significant ST segment shift was defined as more than 1 mm elevation or a depression of the J-point at the first ballooning. No collateral circulation on the coronary angiogram or 201TI filling on the delayed images were observed on any of the target regions of PTCA. Patients were divided into 2 groups: with (Group A: n = 15) and without (Group B: n = 13) significant ST segment shift during PTCA. A redistribution of TI was observed in 14 (93%) of Group A and 10 (77%) of Group B patients. Incidence of BMIPP redistribution was significantly higher in Group B (11 [85%]) than in Group A (3 [20%]) (p < 0.05). Redistribution of BMIPP means suppression of fatty acid metabolism during exercise stress. Augmentation of glucose metabolism is speculated to be an energy source in ischemic preconditioning.

Angioplasty, Balloon, Coronary↗
PubMed2001

Recurrence of idiopathic thromboembolism during anticoagulant therapy.

Patients with acute pulmonary embolism and venous thromboembolism are usually treated with anticoagulant therapy for at least 3 months as the optimum duration. A patient with recurrent idiopathic venous thromboembolism at the eighth month during anticoagulation (warfarin to target international normalized ratio of 2.0-3.0) is described. The case suggests that patients with idiopathic venous thromboembolism have a high risk of recurrence, even if a strict anticoagulant regimen is followed.

Adult↗
PubMed2001

Fulminant myocarditis in polymyositis.

Cardiac involvement in patients with polymyositis is usually asymptomatic and associated with a mild clinical course. A female patient with muscle weakness and cardiogenic shock, who was diagnosed with polymyositis and fulminant myocarditis, is described. A large amount of methylprednisolone, in addition to intra-aortic balloon pumping and percutaneous cardiopulmonary support, led to the recovery of her cardiac function. However, a massive cerebral embolism occurred and she died. Postmortem histopathological examination showed necroses of muscles and diffuse invasion of mononuclear cells in both the myocardium and the biceps muscle of her arm. Although the mechanism of cardiac dysfunction is not clear, immunosuppressive therapy was effective for fulminant myocarditis in the present case.

Acute Disease↗
PubMed2001

[Effect of olopatadine hydrochloride, a novel antiallergic agent, on the QT interval in dogs].

Olopatadine hydrochloride (olopatadine), a novel antiallergic agent, is effective in the treatment of allergic rhinitis, chronic urticaria, eczema and dermatitis. It has been reported that terfenadine and astemizole cause side effects on the circulatory system such as QT prolongation followed by serious ventricular arrhythmias (torsades de pointes). To investigate the possibility of QT prolongation, we used both conscious normal dogs and hypokalemia-anesthetized dogs under two conditions: 1) olopatadine used alone and 2) olopatadine used in combination with itraconazole, the CYP3A4-inhibiting antifungal agent, in the present investigation. The group treated with terfenadine alone (30 mg/kg, p.o.) and the group treated with a combination of terfenadine (10 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) had a significantly prolonged QT interval. On the other hand, the group treated with olopatadine alone (30 mg/kg, p.o.) and the group treated with a combination of olopatadine (30 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) did not show any significant changes in QT interval. Moreover, olopatadine (1 and 5 mg/kg, i.v.) did not influence the QT interval in hypokalemia-anesthetized dogs. These results suggest that there is very little possibility of QT prolongation as a result of clinically used olopatadine.

Animals↗
PubMed2001

[Pharmacological, pharmacokinetic and clinical properties of olopatadine hydrochloride' (olopatadine), an antiallergic drug].

Olopatadine is a selective histamine H1-receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibited the tachykininergic contraction in the guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine inhibited passive cutaneous anaphylaxis in rats, experimental allergic rhinitis and bronchial asthmatic responses in actively sensitized guinea pigs. Olopatadine exerted no significant effects on action potential duration in isolated guinea pig myocardium and ventricular myocytes. Olopatadine was highly and rapidly absorbed in healthy volunteers. The urinary excretion of olopatadine accounted for not less than 58% and the contribution of metabolism was low in the elimination of olopatadine. Olopatadine was shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, pruritus cutaneous, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000.

Animals↗
PubMed2001

Rhein, an active metabolite of diacerein, suppresses the interleukin-1alpha-induced proteoglycan degradation in cultured rabbit articular chondrocytes.

Diacerein has proved to be effective in the treatment of osteoarthritis. We investigated the effects of rhein, an active metabolite of diacerein, on the degradation of recombinant human interleukin-1alpha (rhIL-1alpha)-induced proteoglycan and matrix metalloproteinases (MMPs) release from rabbit articular chondrocytes. Chondrocytes were treated for 24 h with rhein in the presence of rhIL-1alpha. Rhein suppressed the rhIL-1alpha-induced proteoglycan degradation. In addition, rhein decreased the rhIL-1alpha-induced proMMP-3 production and reduced the MMPs activity. These results suggested that diacerein might have a protective effect on proteoglycan degradation via the suppressive effect of rhein on the production of proMMPs.

Animals↗
PubMed2001

Possible involvement of 5-HT4 receptors, in addition to 5-HT3 receptors, in the emesis induced by high-dose cisplatin in Suncus murinus.

To clarify the mechanism for the severe emesis concomitant with intensive chemotherapy, we investigated the effects of 5-HT3- and 5-HT4-receptor antagonists on the emesis induced by the high-dose of cisplatin in Suncus murinus. The emesis induced by 50 mg/kg of cisplatin was reduced by the oral pretreatment with tropisetron, which is known as a 5-HT3- and 5-HT4-receptor dual antagonist in vitro, with the ID50 value of 0.52 mg/kg. On the contrary, granisetron, a selective 5-HT3-receptor antagonist, did not markedly inhibit the emesis at up to 30 mg/kg. Moreover, GR125487, a selective 5-HT4-receptor antagonist, did not inhibit the emesis. However, co-administration of GR125487 and granisetron significantly reduced the number of emetic episodes. The study of the co-administration of GR125487 with tropisetron showed that GR125487 did not further enhance the inhibitory effect of tropisetron alone, suggesting that the anti-emetic effect of tropisetron is mediated via the blockade of both 5-HT3 and 5-HT4 receptors. These results suggest that both the 5-HT3 and 5-HT4 receptors are involved in the emesis induced by the high-dose of cisplatin in Suncus murinus.

Animals↗
PubMed2001

Involvement of neuropeptides in the allergic nasal obstruction in guinea pigs.

The purposes of the present study were i) to determine whether neuropeptides induce the nasal obstruction in guinea pigs, and ii) to examine the possible involvement of neuropeptides in allergic nasal obstruction. The decrease in nasal cavity volume was determined by acoustic rhinometry as an index of nasal obstruction. In non-sensitized guinea pigs, substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) caused the nasal obstruction 10 to 30 min after their intranasal application. LY303870 (1 mg/kg), a tachykinin NK1-receptor antagonist; SR48968 (1 mg/kg), a tackykinin NK2-receptor antagonist; and CGRP(8-37) (50 nmol/kg), a CGRP1-receptor antagonist, administered intravenously before the intranasal application of the neuropeptides, inhibited the responses induced by SP, NKA and CGRP, respectively. In the guinea pigs sensitized with dinitrophenyl-coupled Ascaris suum allergenic extract, the intranasal antigen challenge caused nasal obstruction. The response was biphasic and consisted of the early phase response (EPR) and the late phase response (LPR), which developed 30 min and 6 h, respectively, after the antigen challenge. Intravenous administration of LY303870 (1 mg/kg) before the antigen challenge inhibited the EPR, while those of SR48968 (1 mg/kg) and CGRP(8-37) (50 nmol/kg) inhibited the LPR. The present results suggest that neuropeptides are involved in the allergic nasal obstruction.

Animals↗
PubMed2001

Inhibitory effect of olopatadine hydrochloride on the sneezing response induced by intranasal capsaicin challenge in guinea pigs.

To investigate the possible inhibitory effect of olopatadine hydrochloride (olopatadine), an antiallergic drug, on the tachykinin-mediated nasal responses, we examined the effect of olopatadine on the sneezing and the nasal rubbing responses induced by intranasal capsaicin challenge in guinea pigs. Olopatadine (10 mg/kg, p.o.) inhibited the sneezing response by 57% without affecting the nasal rubbing one. The antihistamines chlorpheniramine and clemastine did not affect the responses. Morphine caused the inhibition of both responses, which was antagonized by naloxone. These results suggest that olopatadine inhibits the sneezing response by the inhibition of the tachykinin release and not by its antihistaminic action.

Administration, Intranasal↗
PubMed2001

Effects of olopatadine hydrochloride on the cutaneous vascular hyperpermeability and the scratching behavior induced by poly-L-arginine in rats.

Intradermal injections of poly-L-arginine induce cutaneous vascular hyperpermeability and scratching behavior in rats. Recently, we elucidated that the plasma extravasation involved both histamine and substance P, while the scratching behavior involved substance P, but not histamine. This study examined the effects of olopatadine hydrochloride (olopatadine), an antiallergic drug with histamine H1-antagonistic action, on the poly-L-arginine-induced responses. Olopatadine (1 mg/kg, p.o.) significantly inhibited both the plasma extravasation and the scratching behavior, suggesting that its inhibitory effects are mediated by the suppression of neuropeptidergic action as well as histaminic action. Olopatadine seems to be a novel-type drug for the treatment of dermatitis.

Animals↗
PubMed2001

Acute effect of human cardiotrophin-1 on hemodynamic parameters in spontaneously hypertensive rats and Wistar Kyoto rats.

There is considerable evidence to indicate that humoral factors play an important role in the development of left ventricular hypertrophy. Cardiotrophin-1 (CT-1) is a cytokine that has been shown to induce cardiac hypertrophy in a dose-dependent manner. The aim of the present study was to investigate the acute effect of CT-1 on hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) and to study the relationship between the plasma concentration of CT-1 and its hemodynamic effect. Ten-week-old SHR and age-matched WKY were used. Blood pressure (BP), heart rate (HR) and plasma concentration of CT-1 were measured both before and for 60 min after intravenous bolus injection of human CT-1 (10 microg/kg). CT-1 injection significantly decreased BP and significantly increased HR in SHR and WKY. There were significant differences in BP and HR between the two groups at all time points after injection. The lowest BP, highest HR and maximal plasma concentrations of CT-1 were observed in both groups within 10 min after injection. However, after converting the values into the percentage change from their respective baselines, there were no significant differences between the two groups in BP or HR at any time point. There was also no significant difference between the two groups at any time point in the plasma concentration of CT-1. This study indicates that CT-1 decreases BP and increases HR in both SHR and WKY. The most obvious change occurred within 10 min after injection. However, there was no significant difference in the hypotensive effect of CT-1 on 10-week-old SHR and WKY.

Animals↗
PubMed2001

[Intermittent androgen deprivation treatment of prostate cancer restarted at low level of serum prostate specific antigen: a pilot study].

We report a pilot study on a novel protocol of intermittent androgen deprivation (IAD) treatment of prostate cancer (PC), in which androgen deprivation is restarted when serum prostatic specific antigen (PSA) level reached more than 2 ng/ml and is stopped when PSA level decreased below 0.3 ng/ml. Thirty-two patients (aged 60 to 86 years, median 74 years) with prostate cancer (Stage A in 4 patients, B in 20, C in 1, D in 5, and relapse after radical prostatectomy in 2) were treated with IAD. Median serum PSA prior to the start of endocrine therapy was 15.65 (range 2.67 to 306.3) ng/ml. Eleven patients were treated with lutenizing-hormone-releasing hormone (LHRH) agonist alone and 21 were treated with LHRH agonist plus an antiandrogen. Median duration of first endocrine therapy was 572 (range 100 to 1,543) days. Median serum PSA at the start of first off-phase was 0.038 (range 0.003 to 0.489) ng/ml. After a median of 207 days (range 140 to 843) of follow-up, 19 patients were in the first cycle, 9 in the second cycle, 3 in the third cycle, 1 in the fourth cycle. Two patients developed androgen-independent PC. The median duration of first off-phase of IAD was 287 days. There was a significant inverse relation between the duration of the first on-phase and testosterone level measured 4 months after the cessation of first on-phase therapy (R = -0.518). These results suggest that our protocol provides a reasonable length of off-phase duration and that the long term-androgen deprivation phase might delay the recovery of the testicular endocrine function which should be maintained during the off-phase of IAD.

Aged↗
PubMed2001

Influence of the angiotensin II receptor antagonist losartan on diuretic-induced metabolic effects in elderly hypertensive patients: comparison with a calcium channel blocker.

OBJECTIVE: Diuretic therapy frequently induces undesirable biochemical changes and side effects. We compared metabolic effects of a low-dose diuretic (D) given in combination with an angiotensin II receptor antagonist, losartan (L), with those resulting from a diuretic given in combination with a calcium channel blocker, slow-release nifedipine (N). MATERIAL AND METHODS: Thirty-seven elderly patients with mild to moderate hypertension (mean age: 71 +/- 3 years) were treated with either L+D (n = 18) or N+D (n = 19) for 1 year. Diuretic therapy included low-dose trichlormethiazide or low-dose furosemide in numbers of patients that were similar between L+D and N+D groups. Blood pressure, serum electrolytes, uric acid, blood glucose, renal function and lipid parameters were measured at baseline, 6 months and 1 year. RESULTS: Effective blood pressure control was observed in both groups at 6 months, and with further improvement at 1 year. Serum potassium was significantly decreased from baseline at 6 months (p < 0.01) and 1 year (p < 0.01) in the N+D group, but not in the L+D group. Serum uric acid was significantly increased from baseline at 6 months (p < 0.01) and 1 year (p < 0.01) in the N+D group, but had minimally decreased at 1 year in the L+D group (p < 0.1). Blood glucose, renal function and lipid parameters did not change in either group. CONCLUSION: The combination of losartan and low-dose diuretics effectively treated hypertension in elderly patients while minimizing the metabolic consequences of diuretic therapy. Larger trials will be necessary to confirm this finding.

Aged↗