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Biomedical subjects

A Mead

Publications and source records attributed to A Mead.

At least 37 records · Page 2Linked to original sources
PubMed1996

Regulation and bioelectrical effects of cyclic adenosine monophosphate production in the ciliary epithelial bilayer.

PURPOSE: To determine whether the intact isolated ciliary epithelial bilayer retains the alpha-2 and beta adrenergic receptor activation and interaction described for whole ciliary processes and whether this pure epithelial bilayer displays bioelectric parameters sensitive to alterations in cyclic adenosine Monophosphate (cAMP) production induced by adrenergic compounds. METHODS: The intact ciliary epithelial bilayer of the rabbit eye isolated by perfusion was mounted in a specially constructed Ussing-type chamber. The transepithelial potential difference and short-circuit current were monitored for effects induced by agents that stimulated or blocked (some did both) caMP production. Using a radioimmunoassay, the latter were studied in the pure epithelial bilayers and in whole ciliary processes. RESULTS: A reproducible increase in cAMP production and an increase in the short-circuit current induced in the bilayer by isoproterenol, a nonspecific beta adrenergic agonist, were both blocked by pretreatment with either timolol, a nonspecific beta adrenergic blocking agent, or with para-aminoclonidine, an alpha-2 agonist. Maximal stimulation of cAMP with forskolin in this pure isolated epithelial preparation yields a response that is 60% of the value found in whole processes, indicating that the latter tissue contains responsive sites that are nonepithelial, probably vascular, or perhaps stromal. The degree of inhibition of the beta adrenergic receptor by alpha-2 agonists was not very different in the two preparations. On the other hand, inhibition of the epithelial vasointestinal peptide receptor by neuropeptide Y or alpha-2 agonism was considerably heightened in the pure bilayered epithelial preparation. CONCLUSIONS: The isolated intact ciliary epithelial bilayer, when stimulated with beta adrenergic receptor agonists, vasointestinal peptide, or forskolin, produces increased cAMP and its transepithelial potential becomes hyperpolarized. These chemical and bioelectrical effects are prevented by pretreatment with either alpha-2 adrenergic agonists or beta adrenergic blocking agents. The results obtained in the isolated intact purely epithelial ciliary bilayer confirm that the ciliary epithelium is the source of adrenergic receptor activation and interaction and support the hypothesis that aqueous humor production is regulated by interactions between epithelial alpha-2 and beta adrenergic receptors.

Adrenergic alpha-Agonists↗
PubMed1995

Repeated ECS differentially affects rat brain 5-HT1A and 5-HT2A receptor expression.

We investigated the effect of electroconvulsive shock (ECS), administered five times over 10 days, on 5-HT1A and 5-HT2A receptor mRNA and binding site densities in the rat brain using in situ hybridization histochemistry and quantitative autoradiography. ECS treatment increased 5-HT1A receptor mRNA abundance and binding site densities in the dentate gyrus, but decreased these parameters in the CA3c layer of the hippocampus. No changes in 5-HT1A receptor mRNA and binding sites occurred in other hippocampal subfields, neocortex or raphe nuclei. Repeated ECS was also found to increase 5-HT2A receptor binding site densities in the neocortex and this was accompanied by a non-significant increase in cortical 5-HT2A receptor mRNA abundance. Our study demonstrates that in the rat, repeated ECS produces anatomically and molecularly discrete effects on 5-HT1A and 5-HT2A receptor gene expression. These changes may be relevant to the therapeutic effect of repeated ECS in depression.

Animals↗
PubMed1991

The isolated ciliary bilayer is useful for studies of aqueous humor formation.

An intact ciliary epithelial bilayer has been isolated from the rabbit eye by perfusion, microsurgical dissection, and recovery techniques. Vital subcellular organelles and intercellular junctions of this epithelial bilayer preparation are very well preserved. The total electrical resistance of the epithelial bilayer is 350 ohms, and the transepithelial potential is 650 microV, nonpigmented epithelium side negative. The electrical resistance is reduced by 0.2 mM EGTA and the transepithelial potential reduced by 0.1 mM ouabain. Bicarbonate depletion at a constant pH of 7.4 rapidly and significantly reduces the transepithelial potential. Carbonic anhydrase inhibitors decrease transmembrane potential by as much as 30%. These morphologic and physiologic experiments authenticate the validity of this bilayered epithelial preparation for future use in detailed studies of the mechanism of aqueous humor formation.

Animals↗
PubMed1989

Adenylate cyclase stimulation and intraocular pressure reduction by forskolin analogs.

Forskolin and 18 chemical analogs of forskolin were assayed for stimulation of adenylate cyclase activity in vitro and for their effects on intraocular pressure (IOP) in vivo. Adenylate cyclase activity was determined with a preparation of corpora striata from male Wistar rats and test drug concentrations of 0.3 to 300 microM. IOP effect was monitored after a single topical ocular application of a 1% suspension of the test drug to male New Zealand albino rabbits. Significant reductions in IOP occurred with compounds which had potent cyclase stimulatory properties. Most compounds with little cyclase stimulatory effect produced little or no decrease in IOP. A 1-substituted morpholino-acetoxy derivative, which may be a prodrug metabolized to active form by corneal esterases, showed little cyclase stimulation in vitro but produced significant reductions in IOP.

Adenylyl Cyclases↗
PubMed1987

Celiprolol versus timolol and placebo: a two week double-blind comparison.

Celiprolol (5%) was compared to timolol (0.5%) and placebo in patients with primary open angle glaucoma or ocular hypertension. A total of 28 patients participated in this double blind study and received treatment for two weeks. Intraocular pressure decreased an average of 4.4 mmHg with celiprolol and 7.1 mmHg with timolol two hours after instillation. This was maintained 12 hours after administration of timolol but not after celiprolol. There was a small but statistically significant decrease in pulse rate 2 hours after administration of timolol (from 72 to 64 beats per minute) which was not observed after celiprolol. Side effects were mild and similar for all 3 groups.

Adrenergic beta-Antagonists↗
PubMed1987

Chorionic gonadotropin decreases intraocular pressure and aqueous humor flow in rabbit eyes.

The effect of human chorionic gonadotropin (hCG) on the rabbit eye was studied. Intravitreal injections of hCG in albino rabbits provoked a reduction of intraocular pressure (IOP). Intravenous administration of hCG in single doses of 5,000-10,000 units in male pigmented rabbits caused a significant reduction in IOP from 1.5-5 hr after injection. When two successive intravenous doses of 5,000 units of hCG were given at 0 and 3 hr to pigmented rabbits, a significant reduction of net aqueous flow occurred, as measured by scanning fluorophotometry. These results indicate that the decrease in aqueous flow rate in the rabbit eye after administration of hCG can account for the reduction in IOP.

Animals↗
PubMed1985

Neovascularization produced by angiotensin II.

Following vascular occlusion, development of collateral circulation occurs in at least two time-related phases: (1) the fast enhancement of the function of preexisting channels and (2) the slow formation of new vessels. Inasmuch as the renin-angiotensin system can act as a protective mechanism against local ischemia by activating preexisting collateral vessels, it is of interest to establish whether angiotensin II also produces stimulation of new vessel formation. Angiotensin II or cholecystokinin, an unrelated peptide, was incorporated in a slow-release formulation polyacrylamide gel and implanted in a pocket made in the rabbit cornea. Periodic examinations revealed that angiotensin II significantly stimulates new vessel formation; maximum values were attained in approximately 2 to 3 weeks. In contrast, cholecystokinin or polyacrylamide gel alone failed to stimulate any significant new vessel formation. Positive neovascularization was present in 85% of the total number of corneas implanted with angiotensin II, whereas 14% and 8% positive results were seen in the corneas implanted with either cholecystokinin or polyacrylamide gel alone, respectively. It is concluded that angiotensin II not only facilitates the activation of preexisting collateral vascular pathways but also has angiogenic properties and therefore could play an active role not only in the fast but also in the slow phase of the development of collateral circulation.

Acrylic Resins↗
PubMed1984

Aqueous flow in human eyes is reduced by forskolin, a potent adenylate cyclase activator.

Forskolin, which lowers intraocular pressure in rabbits, monkeys, and human subjects, was tested for its effect on the rate of aqueous humor flow and on outflow facility. Topical sodium fluorescein was used to measure the rate of aqueous humor flow in forskolin or placebo treated eyes. Tonography was used to determine outflow facility before forskolin administration and at 3 hr after administration of the drug. In eight human subjects who showed reduction of intraocular pressure in response to a single drop of forskolin, flow was reduced by an average of 34%, compared to the contralateral eye during the same period of time. No significant change in outflow facility occurred. The action of forskolin in reducing intraocular pressure was the direct result of a reduction in net aqueous flow.

Adenylyl Cyclases↗
PubMed1984

Ocular blood flow in phakic and aphakic monkey eyes.

Alterations in regional ocular blood flow produced by topical epinephrine were studied in phakic and aphakic eyes of Macaca arctoides using the radioactive microsphere technique. Three isotopes were used to make sequential blood flow measurements just prior to topical epinephrine administration, 1 hr later and 3 hr later. Significant reductions of flow were found in the iris, ciliary body, and optic nerve head of both phakic and aphakic groups. Choroidal and posterior optic nerve flow decreased significantly in aphakic eyes only. Decreases in flow were flow decreased significantly in aphakic eyes only. Decreases in flow were maximal at 3 hr. Significant changes in retinal flow were not detected. The implications of these findings regarding epinephrine-induced aphakic cystoid macular edema and the suitability of epinephrine or its derivatives in the treatment of glaucoma are discussed.

Animals↗
PubMed1984

Forskolin lowers intraocular pressure by reducing aqueous inflow.

Forskolin is a diterpene derivative of the plant Coleus forskohlii that stimulates adenylate cyclase activity without interacting with cell surface receptors. Forskolin lowers the intraocular pressure of rabbits, monkeys, and humans. In rabbits, net aqueous humor inflow decreases, outflow facility remains unchanged, and ciliary blood flow increases. Tolerance to the intraocular pressure lowering effect did not occur in rabbits after topical doses given every 6 hr for 15 days. In vitro forskolin activates adenylate cyclase of crude particulate homogenates prepared from cultured human ciliary epithelia or from dissected ciliary epithelial processes of rabbit or human eyes. This activation is not blocked by timolol. The stimulation of adenylate cyclase by isoproterenol in vitro is potentiated in the presence of forskolin. Forskolin represents a potentially useful class of antiglaucoma agents differing in molecular mechanism of action from previously used drugs.

Adenylyl Cyclases↗
PubMed1983

A major pathway for the regulation of intraocular pressure.

There has been a suspicion on the part of many clinicians and research scientists that intraocular pressure can be regulated by neural and/or humoral influences upon the rate of aqueous humor formation. It has been difficult, if not impossible, to separate specific influences of the central nervous system upon intraocular pressure from vascular induced or other secondary alterations. The past two decades have witnesses a great deal of study of the role of the adrenergic nervous system upon the regulation of intraocular pressure. From the investigations it is possible to formulate an integrated concept that can place years of work and speculation on a firm molecular foundation. The secretory tissue of the eye, the ciliary processes, contain an enzyme receptor complex, comprised by receptor complex, comprised by receptor bound membrane proteins, the catalytic moiety of the enzyme, a guanyl nucleotide regulatory protein (or N protein) and other features. The enzyme can be activated by well known neurohumoral or humoral agents that consist of catecholamines, glycoprotein hormones produced by the hypothalamic pituitary axis, and other related compounds, including placental gonadotropin. These compounds cause the ciliary epithelia to produce cyclic AMP at an accelerated rate. Cyclic AMP, as a second messenger, causes, either directly or indirectly, a decrease in the rate of aqueous humor formation that may be modulated by cofactors. Clinical syndromes fit the experimental data so that an integrated explanation can be given for the reduced intraocular pressure witnessed under certain central nervous system and adrenergic influences. The molecular biology of this concept provides important leads for future investigations that bear directly both upon the regulation of intraocular pressure and upon glaucoma.

Adenylyl Cyclases↗
PubMed1981

Intraocular pressure and aqueous flow are decreased by cholera toxin.

Delivery of 2.1 microgram of cholera toxin, a specific, irreversible activator of adenylate cyclase, via the blood lowers IOP from 17.4 to 11.2 mm Hg in 81/2 hr. decreases net aqueous flow by about 50% in 8 hr, and doubles blood flow to the anterior uvea at 8 to 13 hr. Intravitreal injection of 0.26 microgram of cholera toxin lowered IOP from 15.0 to 9.6 mm Hg, but heat-inactivated toxin had no effect on IOP. The toxin activates adenylate cyclase from ciliary processes 2.2-fold and stimulates cyclic AMP production by ciliary processes 7.4 times. Absence of aqueous flare, normal protein concentrations in the aqueous, and histologic examination all confirmed the functional and structural integrity of the blood-aqueous barrier after cholera toxin infusion. The data point to an important role for ciliary process adenylate cyclase in regulation of aqueous flow and maintenance of IOP.

Adenylyl Cyclases↗
PubMed1980

Non-contact evaluation of carotid artery flow.

We have developed a non-contact system of interrogating the cornea by monitoring the pressure pulse transmitted from the carotid artery. using new electronic developments such as the phase-lock loop, coupled with computer technology and ultrasound, we have produced an experimental curve for progressive stenosis of the carotid artery in animals. Using known physical laws and accepted mathematical principles, we generated the theoretical curve for that same type of progressive occlusion of the carotid artery and have found a high degree of correlation, within 4.5 per cent error.

Animals↗
PubMed1979

Increased pressure after paracentesis of the rabbit eye is completely accounted for by prostaglandin synthesis and release plus pupillary block.

Paracentesis of the anterior chamber of the rabbit eye results in hyperemia, increased protein in the aqueous, elevated intraocular pressure, and miosis. Aspirin does not affect miosis but attenuates the pressure and protein response by about 60%. Pupillary block resulting from miosis aggravates the rise in intraocular pressure (as does mydriasis). Pretreatment with aspirin plus iridectomy virtually eliminates the elevation of intraocular pressure consequent to paracentesis.

Animals↗
PubMed1979

An interophthalmic communicating artery as explanation for the consensual irritative response of the rabbit eye.

An arterial connection between the two internal ophthalmic arteries in the rabbit was confirmed. The consensual response to ocular injury and its relationship to this interconnecting artery was examined by transecting the interconnecting vessel and creating a monocular injury by anterior chamber paracentesis. In the rabbits of two control groups (those undergoing sham operation without vessel ligation and those undergoing no operation) there was a rise in protein in the aqueous of the uninjured eye. In the rabbits with the communicating artery transected, no such rise in contralateral aqueous protein occurred. It is concluded that in the rabbit this vascular connection can explain the contralateral hyperemia and aqueous protein increase seen after monocular trauma.

Animals↗
PubMed1976

The effect of dopamine on the intraocular pressure and pupil of the rabbit eye.

The presence of a dopamine-specific receptor that can influence intraocular pressure in the rabbit eye is suggested by these experiments: intravitreal, systemic, or topically administered dopamine solutions can produce a decrease in intraocular pressure that is dose-dependent. In high doses the decrease in intraocular pressure is accompanied by mydriasis, and alpha-adrenergic pupillary response. This alpha-response may be caused by dopamine as a direct, but weak alpha-stimulator or by displacement of norepinephrine onto the receptor from its storage site. At lower doses the decrease in intraocular pressure occurs in the absence of mydriasis and in spite of blockade of beta-adrenergic receptors. Further, a specific dopaminergic blocker, haloperidol, prevents this decrease in intraocular pressure. The decreases are small, but reproducible and suggest that dopamine can influence the adrenergic regulation of intraocular pressure.

Administration, Topical↗
PubMedDate not supplied

Proposition 215: a dilemma.

The author describes the scope of California's Proposition 215 and explains the legal and scientific controversies that surround its enactment. The federal government's response to the law (including its threats to any physicians who might recommend medical marijuana to patients) and the litigation that ensued are outlined. The author recounts the complicated role played by the California Medical Association during this time, as it sought to adhere to the principles of the scientific process while also attempting to resist improper governmental intrusion into the physician-patient relationship. The legal impact of the federal Controlled Substances Act on the availability of marijuana for either research or therapeutic purposes is described. The conflict between Proposition 215 and federal law is explained, and author offers a legal analysis of the extent to which physicians have free speech rights under the federal constitution to discuss and recommend the medical use of marijuana to patients. The California Medical Association's efforts to address and reconcile the competing interests, culminating in written legal guidelines for physicians, are described in detail.

California↗