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H Ohtaka

Publications and source records attributed to H Ohtaka.

At least 37 records · Page 2Linked to original sources
PubMed1989

Benzylpiperazine derivatives. XI. Synthesis of compounds related to the metabolites of 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride (KB-2796).

The metabolites of 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride (KB-2796, 1), a cerebral vasodilator, and related compounds were synthesized to confirm the proposed structures. The structures of the metabolites (3-5) in rats were identified by means of synthesis of the authentic compounds.

Animals↗
PubMed1989

Syntheses of the metabolites of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-1H benzimidazole difumarate (KG-2413) and related compounds.

The metabolites of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-1H-b enzimidazole difumarate (KG-2413), which has a potent H1-antihistaminic activity, were predicted on the basis of metabolic studies of related compounds and were synthesized to aid in identification of the actual metabolites and for examination of their antihistaminic activity. Among the twelve compounds prepared, nine compounds were actually found as the metabolites of KG-2413 in rat urine. The antihistaminic activities of these metabolites were found to be lower than that of KG-2413.

Animals↗
PubMed1989

Quantitative structure-activity relationships of H1-antihistaminic benzimidazole derivatives.

The quantitative structure-activity relationships (QSAR) of 2-(4-substituted-1-piperazinyl)benzimidazole derivatives for antihistaminic activity were examined. Taking into consideration the specific conformations of some derivatives, a significant correlation was obtained using Verloop's STERIMOL parameters B3 and L of the substituent at the 1-position of the benzimidazole nucleus. The results indicated that the derivatives having a substituent with a small breadth and an appropriate length at the 1-position showed potent activity. From the results, a model of the binding site is proposed. The QSAR of side effects (anticholinergic activity and central nervous system depressive effect) were also examined and the results showed that a sterically small substituent at the 1-position was required to decrease side effects.

Animals↗
PubMed1989

[Clinical significance of intracranial hemorrhage caused by cerebral arteriovenous malformations: with special reference to intraventricular hemorrhage].

Forty-two cases with intracranial hemorrhage caused by cerebral arteriovenous malformation (AVM), which was diagnosed by CT scan, were reviewed with regard to the clinical significance of intracranial hemorrhage, especially intraventricular hemorrhage (IVH). Twenty-one patients were defined as poor risk cases whose level of consciousness at admission was 100 to 300 according to the Japan Coma Scale, whereas the remaining 21 patients were defined as good risk cases. Surgical excision of AVM was undertaken in 35 out of the 42 cases. Urgent surgical removal of intracerebral hematoma and AVM within 24 hours following onset was undertaken in 11 cases. In 14 patients, urgent continuous ventricular drainage was carried out. The effects of the following factors on the level of consciousness at admission, and on the result of AVM treatment were investigated to clarify the clinical significance of intracranial hemorrhage; 1) cast formation of 3rd and/or 4th ventricle, 2) volume of intraventricular hematoma, 3) accompanying intracerebral hematoma and 4) acute hydrocephalus. It was confirmed that all these factors significantly contributed to the development of serious disturbance of consciousness in the acute stage following intracranial hemorrhage. For good risk cases, the rate of patients who showed a good recovery or only moderate disability according to the Glasgow Outcome Scale reached 91%, whereas for poor risk cases, it was only 43%. The presence of large intracerebral hematomas of more than 4 cm in diameter accompanied with IVH was significantly correlated with the result of AVM treatment. The presence or absence of cast formation of 3rd and/or 4th ventricle, volume of intraventricular hematoma and acute hydrocephalus were not significantly related to the result of AVM treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Mechanical properties of porcine intralobar pulmonary arteries.

The isobaric and isovolumetric properties of intrapulmonary arteries were evaluated by placing a highly compliant balloon inside arterial segments. The passive pressure-volume (P-V) curve was obtained by changing volume (0.004 ml/s) and measuring pressure. The isobaric active volume change (delta V) or isovolumetric active pressure change (delta P) generated by submaximal histamine was measured at four different transmural pressures (Ptm's) reached by balloon inflation. The maximal delta P = 11.2 +/- 0.6 cmH2O (mean +/- SE) was achieved at 30.8 +/- 1.2 cmH2O Ptm and maximal delta V = 0.20 +/- 0.02 ml at 16.7 +/- 1.7 cmH2O Ptm. The P-V relationships were similar when volume was increased after either isobaric or isovolumetric contraction. The calculated length-tension (L-T) relationship showed that the active tension curve was relatively flat and that the passive tension at the optimal length was 149 +/- 11% of maximal active tension. These data show that 1) a large elastic component operates in parallel with the smooth muscle in intralobar pulmonary arteries, and 2) the change in resistance associated with vascular expansion of the proximal arteries is independent of the type of contraction that occurs in the more distal arterial segments.

Animals↗
PubMed1988

Effects of KB-2796, a new calcium antagonist, and other diphenylpiperazines on [3H]nitrendipine binding.

The effect of KB-2796, a new diphenylpiperazine calcium antagonist, on [3H]nitrendipine ([3H]NTD) binding was investigated in synaptosomal membranes prepared from the guinea pig cerebral cortex. KB-2796 inhibited [3H]NTD binding in a dose-dependent manner with an IC50 value of 86 nM. In this respect, KB-2796 was the most potent among the diphenylpiperazine derivatives tested. Saturation binding data indicated that this inhibition resulted from a decrease in the binding affinity without changes in the maximal number of binding sites. KB-2796, however, significantly increased the dissociation rate constant of [3H]NTD from radiolabeled membranes. This finding suggests that KB-2796 inhibits [3H]NTD binding by a negative heterotropic allosteric mechanism. Other diphenylpiperazines tested also showed similar inhibitory properties. Diphenylpiperazines may act at a site, which is different from the 1,4-dihydropyridine binding site, on the voltage-dependent calcium channel.

Animals↗
PubMed1988

Serial changes in acute extradural hematoma size and associated changes in level of consciousness and intracranial pressure.

The authors report the cases of 37 patients encountered during the past 4 years who exhibited acute extradural hematoma but were initially treated conservatively because no or only small hematomas were observed on admission. The frequency of hematoma enlargement, hematoma size, and changes in the level of consciousness and intracranial pressure (ICP) were examined in these patients. The hematomas enlarged in 24 (64.9%) of the 37 patients, and attained a maximum thickness of 25 mm or greater in 19 patients (51.3%). The level of consciousness could be closely observed during enlargement of the hematomas in 13 patients: the level remained unchanged in eight, deteriorated in two, and improved in three, indicating relative stability in the state of consciousness despite the marked changes in hematoma size. The patients whose hematoma enlarged after the initial examination included three who underwent initial CT examination 5 hours after the injury. In five patients enlargement of extradural hematomas was observed unexpectedly during conservative treatment under ICP monitoring. The ICP also remained stable in three patients until the follow-up examination, but showed a rapid increase in two after a period of stability. However, there was no difference in the final size of the hematomas between the patients showing an increase in ICP and those who did not. These findings suggest that extradural hematomas enlarge progressively at rates varying with the condition of the source of hemorrhage. Moreover, a period of stability in the level of consciousness, such as the lucid interval seen in patients with extradural hematoma, is considered to be a period during which compensatory mechanisms can maintain the stability of the intracranial condition during progressive enlargement of the hematoma.

Adolescent↗
PubMed1988

[A clinical study of severe cases of hemorrhagic cerebral arteriovenous malformations].

The clinical study was undertaken on 24 poor risk patients out of 69 cases with hemorrhagic cerebral arteriovenous malformations, AVMs, and the surgical problems of poor risk patients with the lesions were discussed. The 24 cases, 35%, out of 69 hemorrhagic AVMs cases showed disturbances of consciousness of 3 digits (100-300) according to the Japan Coma Scale at the time of admission. All cases of these poor risk patients were observed less than 24 hours after the onset of the symptoms. Fifteen of these 24 cases showed brainstem signs including anisocoria and/or decerebrate rigidity and/or respiratory arrest. Eighty-three per cent of 24 poor risk patients had serious neurological defects as a result of the first hemorrhage. Therefore, it was impossible to prevent serious state from occurring in poor risk patients. Of the 69 cases with hemorrhagic AVMs, 56 cases were operated upon. Although 90% out of 38 good risk patients whose level of consciousness was 0 to 30 according to the Japan Coma Scale showed good recovery, only 44% of 18 poor risk patients recovered well. It could not be said that the surgical treatment gave satisfactory results for the poor risk patients when compared with the surgical results of the good risk patients. In respect to the location of AVMs, all three poor risk patients with AVMs in the corpus callosum and the ventricles showed good recovery, whereas of the poor risk patients with AVMs in the cerebrum or the cerebellum, only 4 out of 9 cases (44%) and 1 out of 6 cases (17%) showed good recovery respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Comparative effects of leukotrienes on porcine pulmonary circulation in vitro and in vivo.

The present study examined the effect of leukotrienes on porcine pulmonary vasculature both in vivo and in vitro. In vitro studies using isolated vascular strips demonstrated that pulmonary arterial smooth muscle contracted to leukotriene C4 (LTC4), whereas pulmonary vein smooth muscle did not. Pulmonary arterial contraction was due to both the direct action of LTC4 and secondarily generated thromboxane A2 (TxA2). In vivo, LTC4 injection caused a pronounced but transient increase in pulmonary arterial pressure and pulmonary arterial wedge pressure (Ppw), with a smaller effect on left ventricular end-diastolic pressure. Effects of LTD4 were smaller with comparable pressure changes at all three sites, suggesting a primary cardiac effect. Like LTC4, histamine caused a disproportionate increase in Ppw vs. left ventricular end-diastolic pressure. These observations suggest that LTC4 causes pulmonary venoconstriction in vivo despite its lack of effect on pulmonary vein smooth muscle in vitro. This discrepancy may be due to venoconstrictor effects of TxA2 generated from upstream pulmonary arterial vessels.

Animals↗
PubMed1987

Airway responsiveness to intravenous and inhaled acetylcholine in the guinea pig after cigarette smoke exposure.

Exposure of conscious guinea pigs to cigarette smoke results in bronchial hyperresponsiveness. To examine the mechanisms involved, we measured airway responses to increasing doses of intravenous or inhaled acetylcholine in guinea pigs exposed to cigarette smoke (n = 20) or to air (n = 20). After exposure the guinea pigs were anesthetized, paralyzed, and studied in a pressure-sensitive body plethysmograph while ventilated through a tracheostomy. Two and 6 puffs of an aerosol of increasing concentrations (0.05 to 500 micrograms/ml) of acetylcholine were delivered via the tracheostomy. Intravenous acetylcholine was delivered in boluses of 0.1 ml of increasing concentrations (0.5 to 50,000 micrograms/ml) via a catheter in an external jugular vein. Pulmonary resistance (RL), dynamic compliance (Cdyn), and heart rate (HR) were measured at baseline (after aerosolized or intravenous saline) and after each dose of acetylcholine. The peak responses to both inhaled and intravenous acetylcholine were rapid in onset (less than 15 s), short-lived (3 to 4 breaths), and were noncumulative. The baseline RL, Cdyn, and HR were not different in the smoke and air exposure groups. In the intravenous acetylcholine group, there were no differences in RL, Cdyn, and HR responses between the air and smoke exposure groups. In the inhaled acetylcholine group, the dose-response curve was shifted to the left (p less than 0.05) and reached a higher maximal response (p less than 0.01) after smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗