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Biomedical subjects

L Z Bito

Publications and source records attributed to L Z Bito.

116 records · Page 7Linked to original sources
PubMed1966

Factors affecting the distribution of iodide and bromide in the central nervous system.

1. Even when a steady level of (131)I(-) is maintained in the blood for long periods, the uptake by brain and spinal cord is very small, and the possibility that this is due to an active transport of I(-) from brain-tissue to blood has been examined.2. Most of the phenomena, however, can be explained on the basis of a slow passive diffusion across the blood-brain barrier associated with an active transport of (131)I(-) out of the c.s.f. across the choroid plexuses, so that, except possibly for the spinal cord, active transport from central nervous parenchyma into the blood need not be postulated. If it does occur, it contributes very little to the net exchanges between the three compartments, plasma, c.s.f. and extracellular fluid.3. The steady-state distribution of bromide between plasma and c.s.f. is normally such that the concentration in the c.s.f. is only some 70% of that in plasma; it has been shown that this is most probably due to an active transport of Br(-) across the choroid plexuses.

Journal Article↗
PubMedDate not supplied

The mechanism of peptidergic miosis. I. The structural basis of miotic potency among biologically active polypeptides.

The miotic potency of eleven naturally occurring polypeptides and poly-DL-alanine was tested on the isolated anterior segment of hooded rat and golden hamster eyes in order to gain information on the chemical nature of the peptides or classes of peptides which may be regarded as possible mediators of the miotic response of the mammalian eye to chemical irritants or mechanical or surgical trauma. Substance P, P-octapeptide, physalaemin and eledoisin, and eledoisin related peptide were found to be potent miotics on these preparations, yielding ED50 values in the range of 8 to 95 nM and complete pupillary constriction in the range of 100 to 1000 nM. This is comparable to the miotic potency of carbachol or serotonin. All of these peptides share a C-terminal sequence Phe-X-Gly-Leu-Met-NH2 (where "X" is a variable amino acid) which is characteristic of all tachykinins. Six other biologically active peptides or the synthetic poly-DL-alanine had no measureable miotic effect on these preparations up to a final concentration of 1000 to 10,000 nM. The miotic effect of SP on the rat iris was effectively, but not completely antagonized by the presence of 10(-7)M atropine sulfate in the incubation medium. Preliminary results indicate that the miotic effect of physalaemin, eledoisin and eledoisin related peptide on the anterior segment of rat eyes is similarly antagonized by atropine.

Animals↗
PubMedDate not supplied

The effects of prostaglandins and arachidonic acid on the electroretinogram: evidence for functional cyclooxygenase activity in the retina.

The effects of intravitreally injected prostaglandins (PGs) and arachidonic acid (AA) on the electrical activity of the retina were studied by monitoring the electroretinogram (ERG) of rabbits. In normal rabbits, intravitreal injection of PGE1, PGE2, or AA caused a gradual depression of b-wave amplitude as measured either in low (2 lux) or normal (300 lux) background illumination: up to 45% depression was observed within 1 hr and no recovery was noted during 4 hr of monitoring. The depression of the b-wave amplitude after the intravitreal injection of AA and PGs was similar in time course. Bromcresol green, an inhibitor of PG transport, significantly potentiated the effects of low doses of PGE1 and PGE2 and, to a lesser extent, that of AA. Indomethacin, a known inhibitor of cyclooxygenase activity, prevented the AA-induced, but not the PG-induced depression of the b-wave amplitude. It is concluded that PGs can have a direct effect on the retina and that this region of the eye contains sufficient cyclooxygenase activity to produce pathophysiologically significant amounts of PGs and/or related autacoids.

Animals↗
PubMedDate not supplied

The penetration of exogenous prostaglandin and arachidonic acid into, and their distribution within, the mammalian eye.

The distribution of 3H and 14C activities in intraocular fluids and tissues was studied after topical application of 3H-prostaglandin F2 alpha (3H-PGF2 alpha) and/or 14C-arachidonic acid (14C-AA) to rabbit eyes; intravenous (i.v.) infusion of 3H-PGF2 alpha into rats; and after incubation of rat or rabbit globes in media containing these and other tracers. Thirty min after topical application of 14C-AA, the order of distribution of 14C per unit of tissue weight was cornea much greater than sclera congruent to ciliary body congruent to iris congruent to aqueous greater than retina-choroid greater than vitreous greater than lens. The distribution of 3H was sclera greater than cornea greater than retina-choroid congruent to ciliary body greater than aqueous greater than vitreous (lens congruent to 0; iris congruent to 0). After i.v. infusion of 14C-sucrose and 3H-PGF2 alpha into rats for 1 to 5 min, the globe/blood ratio of 3H was significantly lower than that of 14C. When isolated rat globes were incubated, the order of tracer uptake into the whole globe was AA greater than thiourea greater than PGF2 alpha greater than sucrose, while the order of entry into the aqueous was thiourea greater than sucrose greater than AA greater than -PGF2 alpha. The isolated rabbit cornea accumulated large amounts of 14C-AA which was not readily elutable and much smaller amounts of 3H-PGF2 alpha which was readily elutable. It is concluded that the sclera is highly permeable to PGF2 alpha, but that the cornea is an effective permeability barrier to this, and presumably all other PGs. The passage of AA through the outer coats of the globe is limited by its chemical incorporation into the cornea, sclera and conjunctiva. Thus, inhibition of the adverse intraocular effects of topically applied AA by topically applied drugs may only reflect the ability of these drugs to inhibit the synthesizing capacity of the superficial layers of the globe rather than that of the anterior uvea and other intraocular tissues.

Absorption↗
PubMedDate not supplied

The pathophysiology of the ocular microenvironment. I. Preliminary report on the possible involvement of copper in ocular inflammation.

The concentration of copper [( Cu]) in the extracellular fluid compartments of rabbit eyes was found to increase approximately 30-fold during experimental uveitis, generally paralleling increases in [protein]. However, during the recovery phase the decrease in [Cu] lags behind the decrease in [protein] in some rabbits, suggesting the presence of abnormally high levels of non-protein-associated Cu. Intravitreal injection of CuSO4 (6 micrograms of Cu/eye) causes an inflammatory response and evidence of tissue damage. A better understanding of trace element metabolism is clearly required to further elucidate the mechanism of ocular inflammation and associated tissue damage.

Animals↗
PubMedDate not supplied

The ocular effects of prostaglandins and the therapeutic potential of a new PGF2 alpha analog, PhXA41 (latanoprost), for glaucoma management.

In the early days of prostaglandin (PG) research, the infusion of large PG doses into rabbit eyes already traumatized by cannulation, led to the conclusion that PGs have a profound ocular hypertensive effect that is associated with a breakdown of the blood-aqueous barrier. In contrast, repeated topical application of PGs to nontraumatized eyes of several species other than rabbits has later been shown to yield a maintained ocular hypotensive effect, without barrier breakdown. Due to its excellent pharmacokinetic properties, the isopropyl ester form of PGF2 alpha (PGF2 alpha-IE) is a much more potent ocular hypotensive agent and appeared to be better suited for the management of glaucoma, than PGF2 alpha itself or any currently used glaucoma drug. However, even this prodrug caused clinically unacceptable foreign-body sensation and conjunctival hyperemia, which could be reduced, or eliminated, only by some modifications of the omega chain of PGF2 alpha-IE. One such analog, PhXA41, maintained highly significant IOP reduction in glaucoma patients even with once-daily application at the remarkably low concentration of 0.006%. Because PhXA41 reaches intraocular tissues and the systemic circulation in its de-esterified free-acid form, which is a good substrate for the PG transport system, it retains the most important pharmacokinetic advantages of topically applied PGF2 alpha-IE. However, its greatly reduced side effects give PhXA41 a clear therapeutic advantage over PGF2 alpha-IE, making it an effective new drug candidate for the long-term medical management of glaucoma.

Animals↗