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Biomedical subjects

D L Krohn

Publications and source records attributed to D L Krohn.

At least 19 recordsLinked to original sources
PubMed1982

Liposomes in topical drug delivery.

The possible use of liposomes as topical drug delivery vehicles for both water- and lipid-soluble drugs has been investigated. Data for two characteristic drugs, penicillin G and indoxole, are presented. Liposome uptake by the cornea is greatest for positively charged liposomes, less for negatively charged liposomes, and least for neutral liposomes, suggesting that the initial interaction between the corneal surface and liposomes is electrostatic adsorption. Positively charged unilamellar liposomes enhanced transcorneal flux of penicillin G across isolated rabbit cornea more than fourfold. Liposomal entrapment of drug is prerequisite to enhanced transport; corneal penetration was not enhanced when liposomes that were preformed in the absence of drug were mixed with penicillin G immediately before application to the cornea. Although penicillin G is water-soluble, the findings indicate that it secondarily associates with liposome membranes, possibly by insertion of its hydrophobic end into the lipid bilayer. Indoxole, however, was incorporated directly into the membranes of pure phosphatidyl choline liposomes. Liposome-mediated drug flux efficiency after topical instillation in rats was significantly greater than that obtained with equivalent concentration of drug delivered in polysorbate 80. Ten times more drug in polysorbate 80 was required to equal liposome-mediated flux efficiency. The findings suggest that liposomes enhance corneal penetration of drug by adsorbing to the corneal surface, with direct transfer of drug from liposomal to epithelial cell membranes.

Administration, Topical↗
PubMed1982

Lectin-mediated attachment of liposomes to cornea: influence on transcorneal drug flux.

A method to enhance retention of drug-bearing liposomes at the corneal surface under conditions of tear flow was investigated. Mixed brain gangliosides were incorporated into the membranes of phosphatidyl choline liposomes to provide receptor sites for wheat germ agglutinin, a plant lectin that binds strongly to both human and rabbit corneal epithelium. Ganglioside-containing liposomes showed a 2.5-fold increase in their binding to rabbit cornea in vitro when corneas were pretreated with wheat germ agglutinin (500 micrograms/ml), suggesting that the lectin mediates specific binding of these liposomes to the corneal surface. In addition, under conditions of continuous tear flow (1 ml/hr), ganglioside-containing liposomes with entrapped carbachol significantly enhanced carbachol flux across isolated rabbit corneas pretreated with wheat germ agglutinin 90 min after drug delivery. The data support the potential use of liposomes as a vehicle for topical drug flux enhancement.

Animals↗
PubMed1981

Relative blue-light extinction in lens nucleus related to age and cataract.

The extent of visual function loss from nuclear cataractous change can be estimated by observing the extinction of blue light compared to white light as a function of sagittal lens depth in standard slit lamps. Apparent extinction (loss of transmissivity) of 50% or more of the depth of the lens in blue light of maximal intensity compared to white light at minimal intensity is associated with marked visual loss. However, this transmissivity ratio of 0.5 or less also applies if light intensity remains constant and the blue filter is simply moved in and out of the light beam. Therefore, if 50% or more of the lens appears dark to blue-filtered light, nuclear changes have significantly decreased effective visual acuity. Relative blue-light extinction associated with nuclear change that may be amenable to surgical correction can thus be distinguished from the extinction effect caused by age alone.

Adolescent↗
PubMed1981

Fluorescence intensity profile of human lens sections.

The fluorescence intensity profiles of thin cross-sections of human lenses were determined as a function of age by scanning microspectrofluorimetry with blue light excitation close to that available in conventional slit-lamp examination (filter transmission maximum 410 nm). The fluorescence intensity of the entire nuclear region increased with age. The profile of the adult lens was manifested as a plateau, with a depressed inner region. The anterior slope (representing cortex) was nearly always more gradual than the more precipitous posterior slope. The peak fluorescence intensity was usually located at the posterior juxtacortical region. An additional shoulder occasionally appeared in the anterior juxtacortical nucleus. The fluorescence maximum for all ages occurred at 530 nm.

Adult↗
PubMed1980

Inhibition of prostaglandin-induced iritis. Topical indoxole vs indomethacin therapy.

Rat eyes pretreated with 10 microL of topically applied indoxole or 14C-indomethacin, both drugs as 0.5%, 1.0%, and 2.0% solutions in polysorbate 80, were subjected 60 minutes later to an intravitreal injection of 5 microL of 5.0% sodium arachidonate. Following a 30-minute interval, the iris vascular pattern was photographed under the same standardized conditions as in the preinjection control photographs. Comparison of the average diameters of preselected vessels showed indoxole to be more effective than indomethacin in inhibition of iris vascular dilation at all concentrations tested. Intracameral unbound indomethacin concentration was a whole order higher than that of indoxole after comparable doses. The difference in relative effect of the two drugs is neither a function of aqueous concentration nor of aqueous protein binding.

Animals↗
PubMed1980

Limbal pneumatonometry.

A series of comparisons in normal and glaucomatous eyes, all with normal corneas, was made between Goldmann applanation tonometry and Langham pneumatonometry, central and limbal, and with the patient in sitting and supine positions. All measurements were made at one visit with a standardized sequence. All mean pneumatonograph measurements were significantly higher than the corresponding applanation value. However, no significant difference was found between limbal and apical pneumatonograph values in the supine subject. Conversion values relating pneumatonograph measurements and applanation values have been derived and designated as Clinical Correlation Estimators. This allows prediction of Goldmann applanation values by extrapolation of limbal pneumatonograph measurements at a 95% confidence level. The method has potential use in the determination of intraocular pressure in the presence of corneal disease.

Adolescent↗
PubMed1980

Central anterior chamber depth after laser iridectomy.

We found the true anterior chamber depth to be unaffected by successful laser iridectomy in ten eyes treated by this modality for chronic angle-closure glaucoma. The apparent general deepening seemed to be the result of peripheral chamber deepening combined with the common use of strong cycloplegic agents, reversing the shallowing effect of preoperative miotic medications.

Anterior Chamber↗
PubMed1979

Transcorneal flux of topical pilocarpine to the human aqueous.

Aqueous fluid was withdrawn from eyes of patients undergoing cataract extraction at various intervals after administration of two drops of 2% pilocarpine HCl in a standard manner. Determination of aqueous pilocarpine concentration was made both by spectroscopy of a ferric hydroxylamine complex and by gas-liquid chromatography. Results of both methods were consistent in indicating that concentration does not rise at any time following such topical instillation beyond 5 microgram/ml, with an average of 1.67 microgram/ml, representing a flux efficiency of 0.03%. These findings correlate well with previous investigations of transcorneal flux of pilocarpine for the rabbit in a transport chamber system, in which comparable low flux efficiency was found after simulated drop administration. This serves in some measure to validate an extrapolation of other findings in chamber experiments to the living human eye.

Administration, Topical↗
PubMed1979

Enhancement of the sensitivity of the peripheral visual field of aphakic eyes by a soft contact lens correction.

Goldman perimetric field examination was done on 42 glaucomatous eyes, with aphakic spectacles and a soft lens correction. There was a 79% +/- 20% SD overall average enhancement of field size with the soft lens, but the difference varied linearly as a direct function of the initial spectacle field size. There appears to be a significant advantage to the patient in the use of soft lens correction for serial peripheral field measurements.

Aphakia, Postcataract↗
PubMed1978

Flux of topical pilocarpine to the human aqueous.

Aqueous fluid was withdrawn from eyes of patients undergoing cataract extraction at various intervals after administration of two drops 2% pilocarpine-HCl in a standard manner. Determination of aqueous pilocarpine concentration was made both by spectroscopy of a ferric hydroxylamine complex and by gas-liquid chromatography. These methods were consistent in indicating that concentration does not rise beyond 5 micrograms/ml at any time following topical instillation. The mean of 71 GLC determinations of aqueous tapped between 2 and 32 minutes after drops was 1.67 micrograms/ml. With assumption of a total chamber volume of 400 microliter, the average total pilocarpine in aqueous in these circumstances is less than 1 microgram. These findings correlate well with investigations of transcorneal flux of pilocarpine for the rabbit in a partial in vitro transport chamber system, with which comparable low flux efficiency was found after simulated drop administration. This serves to validate in some measure in extrapolation of other findings in chamber experiments to the living human eye. The combined in vitro and in vivo experimental results suggest that two distinct mechanisms govern the flux of pilocarpine across the cornea. High doses, comparable to those in standard clinical use, whether administered in drops or in constant flow, are transported inefficiently with kinetics indicating a diffusional mechanism and are associated with intracorneal retention or degradation of a substantial moiety. Low doses, if continuously applied, are much more efficiently transported. Hydrogel polymer vehicles appear to mobilize this low-dose mechanism by retaining drug against mechanical dissipation and elution by tear flow, but also by retaining drug against the capability of the cornea to take up more pilocarpine than can be transported to produce an intracorneal drug "depot." Although the exact nature of the "depot" is not clear, it is not elutable as pharmacologically active drug. It is consistently associated with the relatively poor flux efficiency found with high doses, and thus may act in some manner to disable a more efficient mechanism. The flux efficiency found with hydrogel mediation is more than double the best found in constant flow determinations. Vehicular mediated flux is rate limited by the cornea, independent of dose, linear with time despite exponentially secreasing available drug, and not associated with an intracorneal drug "depot." These features are consistent with carrier mediation of some type.

Animals↗
PubMed1977

Induction of drug photosensitization in man after parenteral exposure to hematoporphyrin.

Two patients had acute phototoxic reactions after intravenous injections of hematoporphyrin (7 mg/kg) and exposure to light. These reactions were characterized by pain, redness, and swelling of affected sites. Controlled clinical studies were instituted using known types and amounts of light to ascertain the degree of photosensitivity at various time intervals after drug administration. In addition, action spectrum studies elicited a peak response at 405 nm (+/- 5 nm). Plasma hematoporphyrin concentration was approximately 520 microgram/100 ml one hour after hematoporphyrin infusion and it gradually declined during a period of 42 days with a biphasic diminution that suggested the existence of at least two pools of hematoporphyrin with half-life decay times of 16 hours and 12 days. beta-carotene was administered to ascertain whether or not the phototoxic response could be modified. It is suggested that a degree of protection was obtained that was insufficient to protect the patient.

Aged↗
PubMed1976

Variations in fluorescence characteristics of intact human crystalline lens segments as a function of age.

Fluorescence spectra of human lenses were examined as a function of age. The relative intensity in the blue-green area was red shifted with age. Absorption and scatter produce a substantial contribution to this shift. Some change, however, was the result of a true fluorescence intensity shift. In the lower blue region a true independent red shift was found in the nucleus, but not in the cortex. In the upper blue region, true red shift in the nucleus was not significant with fluorescence excited at 400 nm but was significant with fluorescence excited at 375 nm; the shift was well defined in the cortex. This pattern is consistent with age-related accumulation of multiple fluorogens or fluorogen precursors in the lens with relative concentration differences in nucleus and cortex.

Absorption↗
PubMed1976

Quantitation of pilocarpine delivery across isolated rabbit cornea by noncross-linked high viscosity polymer gel.

The effect on pilocarpine flux across rabbit cornea in vitro by a noncross-linked polymeric gel vehicle was measured. A closed system transport chamber was used. Its design featured continuous flow of a tear analog but excluded variables of the internal eye. Results were compared to previously determined data in the same chamber system for cross-linked hydrogel buttons and for free pilocarpine fluid. Gel-mediated flux was equal to that with lens buttons to 90 minutes in the case of a 30 per cent gel (viscosity approximately 70,000 centipoises). Elution by the tear analog system limited flux duration of gels relative to lenses. Greater viscosity of 30 per cent gel relative to 25 per cent gel (approximately 15,000 centipoises) was associated with prolonged transcorneal drug flux. The congruence of flux slopes for 30 per cent gel and lens button vehicles despite the difference in available dose suggests saturable mediation of pilocarpine transport across the cornea, but a greater "flux efficiency" through 90 minutes for 30 per cent gel.

Animals↗
PubMed1975

Quantitation of pilocarpine flux enhancement across isolated rabbit cornea by hydrogel polymer lenses.

The comparative effect on pilocarpine flux across rabbit cornea induced by two hydrogel polymer lenses containing equal doses was quantitated in a transport chamber. This closed system featured continuous flow of a tear analog but excluded variables of the internal eye influencing concentration. Flux induced by both lenses increased linearly with time. At 240 minutes total flux was a whole order greater than that induced by the same pilocarpine dose in free fluid. Analysis of pilocarpine in tear analog effluent showed the flux to be independent of the available dose retained in the hydrogel polymer lens, suggesting that corneal transport of pilocarpine to the aqueous may involve mediation by a carrier system.

Animals↗