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Biomedical subjects

M Oka

Publications and source records attributed to M Oka.

At least 757 records · Page 42Linked to original sources

Bradykinin as an algesic (pain producing) substance in the pulp.

A rat uterine smooth muscle contracting substance was released into the superfusate of the dog's exposed canine pulp after noxious stimulation of the pulp by pricking, heat and electrical stimulation. This active substance was acid- and heat-resistant and was decomposed by carboxypeptidase B and alpha-chymotrypsin, but not by carboxypeptidase A and trypsin. This substance was also tested on several types of smooth muscle. Electrical activity of nerve cells in the reticular formation, which were sensitive to stimulation of the instep of the foot by pinching, was activated by the intrafemoral administration of the active substance. The algesic activity of this substance was examined in cantharidin blister base in man. This study conclusively demonstrated that the active substance of the pulp released by noxious stimulation produced pain and it was identified as bradykinin.

Animals↗

Progesterone interferes with the actions of prostaglandin (PG) E1 but not those of PGE2 or PGF2 alpha in a rat vascular preparation.

In the mammary gland some actions of prolactin seem mediated by PGs. Progesterone blocks several of the mammary effects of prolactin. We therefore investigated the effects of 100 ng/ml progesterone (within the normal human plasma concentration in pregnancy) on the vascular effects of PGE2, PGEF2 alpha and PGE1. Progesterone had no effects on the responses to PGE2 and PGF2 alpha but significantly (p less than 0.01) attenuated the actions of low concentrations of PGE1. It may have enhanced the actions of high PGE1 concentrations. Progesterone appears able to block some effects of PGE1 and to imitate others.

Animals↗

Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. I. Effects of ethanol.

Ethanol, over the concentration range 33 to 300 mg/100 ml (7.2-65.2 x 10-3 M) caused a dose dependent and highly significant enhancement of conversion of 14C-dihomogammalinolenic acid (DGLA) to prostaglandin (PG) El and to thromboxane (Tx) B1 by human platelets. Ethanol had no significant effect on conversion of 14C-arachidonic acid to PGE2 and TxB2. This concentration range is the one involved in human alcoholic intoxication. The effect could be related to enhanced transport of DGLA to the active site of the cyclo-oxygenase enzyme complex, to a modification of the enzyme complex which changes the way it metabolizes DGLA but not arachidonic acid or to two different enzymes. Whatever the mechanism it seems that it is possible to regulate selectively the formation of 1 and 2 series PGs probably at the cyclo-oxygenase level. The physiological and clinical implications of this are discussed.

8,11,14-Eicosatrienoic Acid↗

Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. II. Effects of vitamin C.

Vitamin C over the concentration range 10 to 100 microgram/ml (5.7-57 x 10-5 M) caused a dose dependent and highly significant enhancement of conversion of 14C-dihomogammalinolenic acid (DGLA) to prostaglandin (PG) E1 and to thromboxane (Tx) B1 by human platelets. Vitamin C had no effect on conversion of 14C-arachidonic acid to PGE2 and TxB2. The concentration range is relevant to physiology: in some cells which concentrate the vitamin, such as polymorphonbuclear leucocytes and the adrenal cortex, vitamin C concentrations may be substantially higher than 100 microgram/ml. Vitamin C can therefore selectively enhance the formation of cyclo-oxygenase generated products from DGLA without changing formation of those from AA. This effect can account for a number of the known actions of vitamin C including its effect on the immune system. The implications of this finding are discussed.

8,11,14-Eicosatrienoic Acid↗

The nutritional regulation of T lymphocyte function.

Prostaglandin (PG) E1 plays a major role in the regulation of thymus development and T lymphocyte function and the evidence for this is reviewed. The production of PGE1 is dependent on nutritional factors with linoleic acid, gamma-linolenic acid, pyridoxine, zinc and vitamin C playing key roles. Inadequate intake of any one of these will lead to inadequate PGE1 formation and defective T lymphocyte function. Megadoses of any one are likely to be only minimally effective in the absence of adequate intakes of the others. By careful attention to diet it should be possible to activate T lymphocyte function in the large number of diseases including rheumatoid arthritis, various auto-immune diseases, multiple sclerosis, and cancer in which such function is defective. It is possible that T lymphocytes may require both endogenous and exogenous PGE1 in order to function adequately. It is therefore of particular interest that many cancer cells and virally infected cells are unable to make PGE1 because they cannot convert linoleic acid to gamma-linolenic acid. The direct provision of gamma-linolenic or dihomo-gammalinolenic acids in these situations is worthy of full investigation.

Animals↗

The regulation of prostaglandin E1 formation: a candidate for one of the fundamental mechanisms involved in the actions of vitamin C.

Vitamin C stimulates the formation of PGE1 in human platelets. The effect occurs over the physiologically relevant range of concentrations. PGE1 is required for T lymphocyte function and plays a major part in the regulation of immune responses. PGE1 is also important in the regulation of collagen and ground substance metabolism, in cholesterol metabolism and in regulation of responsiveness to insulin. It is proposed that defective formation of PGE1 could account for many of the features of scurvy and for many of the reported therapeutic effects of vitamin C. If correct, vitamin C will be of value only in conjunction with an adequate supply of dihomogammalinolenic acid, the precursor of PGE1. Essential fatty acids, pyridoxine and zinc are all required to achieve this.

Animals↗

Synthesis of 2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole derivatives and their central nervous system activities.

The synthesis and some pharmacological effects of cis- and trans-2-substituted 2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole derivatives are described. In these derivatives, the substituents of the 2, 5 and 8 position, together with the relative configuration of the 4a and 9b position, influenced the potency of the central nervous system activities. A cis-2-[3-(p-fluorobenzoyl)propyl] analogue (5k) of carbidine (1) possessed not only thymoleptic-like biological activity but had more potent neuroleptic activity than the parent drug.

Animals↗

Alteration of tissue zinc distribution and biochemical analysis of serum following pinealectomy in the rat.

Eight weeks following pinealectomy in adult male Wistar rats, zinc levels of various tissues were found to be significantly altered: zinc in thoracic aorta was significantly increased, and in serum, pituitary, adrenal, heart, lung, and body hair, it was decreased. Serum biochemical analysis indicated that there was a significant elevation of cholesterol, alkaline phosphatase, sodium, urea, and creatinine in serum from pinealectomised rats. Liver, spleen, and thymus weights were lower following pinealectomy, although hearts were increased. The effects of pinealectomy on zinc levels in serum and tissues and on serum cholesterol and alkaline phosphatase may be related to its effects on vascular reactivity and liver fibrosis.

Adrenal Glands↗

Erbium--169 versus triamcinolone hexacetonide in the treatment of rheumatoid finger joints.

Erbium--169 was compared with triamcinolone hexacetonide in the topical treatment of 32 patients suffering from rheumatoid arthritis. Erbium--169 was injected into 83 and triamcinolone hexacetonide into 54 proximal interphalangeal or metacarpophalangeal joints. Both treatments produced alleviation of joint pain and swelling and improvement of grip strength. At every check-up (1--18 months) the percentage of remissions was higher after triamcinolone hexacetonide injection than after erbium--169. The difference was significant at 1, 3, and 6 months.

Adult↗

Differential antagonism of antiavoidance, cataleptic and ptotic effects of neuroleptics by biperiden.

The interaction between neuroleptics and an anticholinergic, biperiden, in the antiavoidance, catalepsy and ptosis tests was investigated in mice for the purpose of predicting the extrapyramidal side-effects of neuroleptics. The cataleptic effect of most neuroleptics used was antagonized to some extent by biperiden, while the ptotic effect was hardly influenced. The antiavoidance effect of haloperidol, trifluperidol and perphenazine was markedly antagonized and that of chlorpromazine moderately. However, the effect of thioridazine, chlorprothixene, levomepromazine and clozapine was little antagonized. In neuropharmacological tests, haloperidol, trifluperidol and perphenazine exhibited a selective antidopaminergic activity, while chlorprothixene, levomepromazine and clozapine showed antidopaminergic, antiadrenergic and also anticholinergic activities when similar doses were given. These results indicate that biperiden antagonism may be marked in the tests related to the extrapyramidal symptoms and in drugs liable to induce extrapyramidal side effects, however, there would be little or no antagonism in drugs possessing the anticholinergic property and eliciting few extrapyramidal side-effects.

Animals↗

Responses of aldosterone-producing adenomas to ACTH and angiotensins.

To elucidate the control mechanism of aldosterone production in primary aldosteronism, in vivo and in vitro studies were done in 7 patients with aldosterone-producing adenomas. In the in vivo study, plasma aldosterone was stimulated more significantly by (Formula: see text), synthetic ACTH than by angiotensin II or furosemide. Diurnal variations of plasma aldosterone, which were studied in 4 patients, were similar to those seen in normal controls. In agreement with the results in the in vivo study, the in vitro study also revealed ACTH stimulated aldosterone and deoxycorticosterone (DOC) from the adenoma more markedly than angiotensin II or III. There was no adenoma which was more sensitivie to angiotenion II or III than to ACTH. From these results it is considered that changes in plasma aldosterone induced by the exogenous administration of angiotensin II or ACTH in patients with aldosterone-producing adenoma are mainly based on changes in aldosterone production in the adenoma. Furthermore, in patients with an aldosterone-producing adenoma in whom diurnal variations of plasma aldosterone similar to those in normal subjects are observed, responses of aldosterone to angiotensin II are supposed to be less than those to ACTH.

Adenoma↗

Vitamin B2 activity of 7,8-dimethyl-10-(2,3,4-trihydroxy-4-formylbutyl)isoalloxazine in Lactobacillus casei.

The microbial activities of vitamin B2-aldehyde and vitamin B2-acid, produced by Schizophyllum commune, a Basidiomycete, were studied. Lactobacillus casei ATCC No. 7469 was used as a test microorganism. B2-aldehyde exhibited a good response curve in the growth of L. casei. B2-acid had neither a stimulatory nor an inhibitory effect on the growth. When B2-aldehyde was incubated with the homogenate of L. casei, it was converted to riboflavin. The flavin formed from B2-aldehyde by the homogenate not only exhibited an equivalent response curve to authentic riboflavin in the growth of L. casei, but also showed the same Rf value as authentic riboflavin in any paper chromatogram, as far as tested. Hence, the microbial activity of B2-aldehyde for L. casei seems to be ascribable to riboflavin which is a reduction product of B2-aldehyde.

Dose-Response Relationship, Drug↗