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Biomedical subjects

H Miichi

Publications and source records attributed to H Miichi.

9 recordsLinked to original sources

Assessment of ocular irritability of liposome preparations.

Ocular irritability of neutral or positively charged liposomes were assessed by the Draize test, histological examination and the rabbit blinking test. The mean total score (MTS) of the Draize test showed a slight increase immediately following instillation of liposome preparations. However, it did not exceed the "practically nonirritating level", and the MTS rapidly became less than the "nonirritating level". No corneal histological alteration was observed by optical microscopy following 9 instillations of each liposome preparation. Although the neutral liposome preparation failed to increase the rabbit blinking count, the positively charged liposome preparation did so to a significant degree. The neutral liposome preparation was confirmed not to give rise to ocular irritation. However, the positively charged liposome preparation may cause pain or unpleasantness following instillation.

Animals↗

Histamine receptors on rat ocular surface.

The role of histamine H1- and H2-receptors in mediating the response produced by histamine was investigated on rat ocular surface. Histamine caused a dose-dependent increase in microvascular permeability on this surface. Response to histamine was significantly inhibited by pretreatment with chlorpheniramine (an H1-antagonist) but was unchanged by cimetidine (an H2-antagonist). No additive effect was shown when chlorpheniramine and cimetidine were used in combination. Moreover, dimaprit, a selective histamine H2-receptor agonist, failed to elicit a dose-dependent vasopermeability response. Chlorpheniramine significantly reduced increase in microvascular permeability associated with immediate hypersensitivity, although cimetidine did not. The addition of cimetidine to chlorpheniramine did not lead to greater reduction than that achieved with chlorpheniramine alone. We conclude that the microvascular permeability response to histamine is predominantly mediated by H1-receptors on rat ocular surface.

Animals↗

Quantitative evaluation of ocular anti-inflammatory drugs based on measurements of corneal temperature in rabbits: dexamethasone and glycyrrhizin.

A method for the quantitative evaluation of topically applied anti-inflammatory agents is described. Conjunctival inflammation was induced in rabbits by topical instillation of n-butanol. The intensity of inflammation was determined by measuring changes of corneal surface temperature with an infrared thermometer. The closest correlation was obtained between corneal temperature change and the Draize score which is widely used as a subjective scoring method. Dexamethasone showed a good logarithmic dose-response inhibitory effect between 0.0001 and 0.1%, and glycyrrhizin the same at 0.25-5%. Glycyrrhizin in a 5% solution showed a comparable anti-inflammatory effect to that of dexamethasone (0.1%). The inflammation model induced by n-butanol was mediated, in part, by the degranulation of mast cells because of some inhibitory effect of disodium cromoglycate (2%), an inhibitor of mast cell degranulation, and diphenhydramine hydrochloride (0.5%), an antihistaminic agent.

1-Butanol↗

Evaluation of an antiallergic agent (disodium cromoglycate) in rat conjunctiva using monoclonal IgE antibody.

The effect of disodium cromoglycate (DSCG) on the anaphylactic reaction was re-evaluated by measuring the amount of leaked dye into tissues of rat conjunctiva 48 h after passive sensitization with IgE antibodies against ovalbumin. In the rat sensitized with mouse monoclonal IgE (titer 4), DSCG produced a dose-dependent inhibitory effect when used in a dose range between 1 and 5%; at more than 2%, the effect was statistically significant. On more severe anaphylactic reactions induced with the same antibody at titer 10, DSCG had no significant effect when applied in doses of less than 5%. On the other hand, DSCG (2%) had no significant effect on the sensitization with either rat polyclonal IgE or mouse polyclonal IgE (titer 4). These findings indicate that DSCG has a potential benefit when used in moderate anaphylactic reactions and has a strictly specific effect depending on the origin of the antibody.

Anaphylaxis↗

Effects of pilocarpine, salbutamol, and timolol on aqueous humor formation in cynomolgus monkeys.

The rate of aqueous humor formation was determined in the cynomolgus monkey eyes by a tracer dilution technique. One 25-gauge needle was inserted into the posterior chamber and a solution of fluorescein labeled dextran with a molecular weight of 40,000 was infused at a constant rate. The aqueous humor was collected through a needle inserted into the anterior chamber, while the intraocular pressure (IOP) was maintained at a constant level. The aqueous humor formation rate and the dye distribution volume were calculated from the time profile of the dye concentration in the effluent aqueous humor. By means of this technique, the effects of pilocarpine, salbutamol, and timolol on the aqueous humor formation rate were studied. The test drug solution was administered into the conjunctival reservoir during a 90-min period before measurements and also during the measurement so that a steady-state drug concentration was maintained in the anterior chamber during the measurement. Pilocarpine 0.1% reduced the aqueous humor formation rate to approximately 50% of the control without significantly changing the IOP or the distribution volume. Salbutamol 0.5%, a beta-adrenergic agonist, increased the rate by about 38%, but timolol 0.1%, a beta-adrenergic antagonist, reduced the rate by an average of 36%. Timolol caused a statistically significant lowering of the IOP by about 2 mmHg. Simultaneous administration of salbutamol 0.5% and timolol 0.2% caused no change in the aqueous humor formation rate or the IOP. The barrier function of the blood aqueous barrier was not altered by these drugs as revealed by aqueous protein determinations.

Albuterol↗

Effects of cholinergic drugs and adrenergic drugs on aqueous humor formation in the rabbit eye.

The aqueous humor formation rate was determined in the anesthetized rabbit with a tracer dilution technique. The anterior chamber was cannulated with two 25-gauge needles: one was inserted into the posterior chamber through the pupil and the other was placed in the anterior chamber near the iridocorneal angle. Fluorescein-dextran solution was infused into the posterior chamber at a constant rate and the aqueous humor was collected through the anterior chamber needle. The aqueous humor formation rate and the volume of dye distribution were calculated simultaneously from the dye dilution curve. Utilizing this technique, the effects of the following substances on aqueous humor formation were studied following topical administration to the conjunctival reservoir: cholinomimetic drugs, pilocarpine and physostigmine; the parasympatholytic drug, atropine; adrenoceptor agonists, norepinephrine, epinephrine, isoproterenol and salbutamol; and beta-adrenoceptor antagonists, timolol and propranolol. Cholinomimetic drugs, i.e., pilocarpine 0.1 mg ml-1 to 10 mg ml-1 and physostigmine 1 mg ml-1, increased the aqueous humor formation rate, while atropine 1 mg ml-1 decreased the rate. The increase in aqueous humor formation by the cholinomimetics was completely antagonized with simultaneous administration of atropine. Norepinephrine 5 mg ml-1 and epinephrine 5 mg ml-1 reduced significantly both the aqueous humor formation rate and intraocular pressure (IOP). Isoproterenol 5 mg ml-1 caused a significant lowering of the blood pressure and IOP and tended to lower aqueous humor formation, although the decrease was not statistically significant. No significant effect on the blood pressure, IOP or aqueous humor formation was observed with isoproterenol 2 mg ml-1. Salbutamol 5 mg ml-1 raised the IOP while timolol 1 mg ml-1 lowered the IOP without any significant change in aqueous humor formation or blood pressure. Timolol 0.5 mg ml-1 or propranolol 5 mg ml-1 did not cause a significant effect on the blood pressure, IOP or aqueous humor formation rate.

Albuterol↗

[Pharmacological studies on basic ethers (R111 and R97) with antispasmodic activity].

Pharmacological properties and acute toxicity of 2-tolyl 1-phenyl-3-(2-methylpiperidino) propyl ether methyl bromide (R111) and 2-chlorophenyl 1-phenyl-3-(2-methylpiperidino) propyl ether methyl iodide (R97) were examined. The results obtained were as follows: (1) In the analgesic effects, RIII and R97 inhibited markedly the acetic acid-induced writhing in mice, but in reducing pain induced by heat, R111 and R97 showed negative results. The local anesthetic effect of R111 was approximately equal to that of procaine. R111 and R97 showed no effects on spontaneous locomotion, the convulsion induced by strychnine or pentetrazol, and normal body temperature. (2) R111 and R97 antagonized acetylcholine, barium chloride, nicotine and serotonine-induced spasm, but not that of histamine and bradykinin. In particular they possessed marked anti-barium chloride activity, where their effects were 20 to 30 times more active than that of papaverine. (3) R111 and R97 indicated weak mydriatic activity. (4) R111 and R97 showed inhibitory effects on the pilocarpine-induced sialic secretion and the propulsive movements of the small intestine, but their inhibitory effects on the gastric secretion were relatively weak. (5) R111 and R97 displayed protective effects in Shay's ulcer, but had no curative effects on acetic acid ulcer. (6) R111 and R97 induced temporary reduction of arterial blood pressure and blood flow immediately after the administration of the test compounds in anesthetized rabbits. However, these agents induced no change in ECG, heart rate and respiration. (7) Intraperitoneally administered R111 and R97 were effective in inhibiting the carrageenin-induced edema in the hind paw of rats. From the above results, it may be considered that R111 and R97 have together strong cholinergic blocking and muscotropic antispasmodic effects, moreover, no significant effects on the central nervous system.

Analgesics↗