Biomedical subjects

J W Huff

Publications and source records attributed to J W Huff.

At least 19 recordsLinked to original sources

PubMed1991

New cryoprotectant for cryorefractive surgery.

Cryorefractive surgeries, keratomileusis, keratophakia, and epikeratophakia cause destruction of keratocytes, which may result in postoperative corneal haze. We examined the effects of two cryoprotectants on keratocyte survival following freeze injury. We compared the ability of CPTES and the standard cryoprotectant KM-26 to prevent keratocyte death by altering the length of time corneal tissue was exposed to the cryoprotectant. When corneal stroma was immersed in CPTES for five minutes prior to freezing, 66.5% of the keratocytes survived; when tissue was immersed in KM-26 for the same length of time, 27.5% survived (P less than .01). Immersion for one to 30 minutes in CPTES prior to freezing produced keratocyte viabilities that were 40% to 80% of those of fresh, unfrozen tissue; immersion in KM-26 produced keratocyte viabilities of 20% to 60%. We compared the ability of these cryoprotectants to reduce corneal haze following freeze injury using our rabbit model of lamellar keratoplasty. The postoperative data were comparable to those in the cell culture experiments. Based on our findings in rabbit corneas, a cryoprotective medium such as CPTES may promote cell survival and thereby speed recovery from cryorefractive procedures in humans.

Animals↗

PubMed1991

Effects of temperature and conditioning on contact lens wetting angles.

Because wettability is not always examined under standard conditions, we investigated the temperature dependence of saline wettability on unconditioned and conditioned polymethylmethacrylate (PMMA), cellulose acetate butyrate (CAB), and three silicone acrylate lens materials. Sessile drop contact angles were measured in a humidity chamber at 23 degrees C and 34 degrees C using laser-assisted contact angle goniometry. In separate experiments, saline-stored and preconditioned lenses were examined either with or without rinsing. Sessile drop contact angles at 34 degrees C were within 2 degrees to 5 degrees of the room temperature values for both conditioned and unconditioned lenses, demonstrating a negligible temperature dependence. At both temperatures, the conditioned PMMA, CAB, silafocon A, and pasifocon C lenses wet slightly better, by 1 degree to 12 degrees, than unconditioned lenses. However, this increase was only significant with PMMA and silafocon A (P less than 0.05) and reversed when the preconditioned lenses were rinsed repeatedly in saline and reexamined. The results suggest that for these materials: 1) in vitro saline contact angles do not approach those seen on the eye, and this discrepancy can not be explained by temperature or conditioning; and 2) conditioning does not increase material wettability but merely forms a temporary hydrophilic interface that is more wettable than the lens material.

Acrylic Resins↗

PubMed1991

Studies on initiation of silicone elastomer lens adhesion in vitro: binding before the indentation ring.

We studied silicone elastomer lens binding in vitro to determine what factors may influence its development on the cornea or corneosclera. Lens binding to corneas was not influenced by corneal toricity (0-20 D), corneal fitting relationship (2 D steep to 4 D flat), mucin (2 or 5%) in the tear-bath, or transcorneal pressure (11-22 mm/Hg). In isolated corneas or in whole eyes, transient intraocular pressure changes did not influence keratometry readings, ruling these out as potential mechanisms for corneal binding during sleep. Corneoscleral preparations were also examined to simulate a decentered lens. Corneoscleral binding occurred with a significantly (P less than 0.001) greater frequency than corneal binding and was not influenced by corneal toricity, corneal fitting relationship (up to .5 mm steeper than K), or mucin concentration. Unlike the final stages of clinical lens adhesion, the binding we observed permitted lateral lens movement and occurred without leaving an indentation ring. These findings may suggest that the system models the initiation of corneoscleral binding, involving decentration and suction onto the corneoscleral junction. Corneal binding, however, cannot be explained by a chemical attraction between the silicone elastomer lens surface and cornea, with or without mucin interaction, and must be accounted for by other factors found in vivo.

Adhesiveness↗

PubMed1991

Contact lens-induced edema in vitro. Pharmacology and metabolic considerations.

The effects of physiologic and pharmacologic manipulations on contact lens-induced edema were studied. In isolated superfused rabbit corneas bathed in Ringer's solution and covered with large-diameter polymethylmethacrylate (PMMA) lenses, corneal swelling rates of 17-26 microns/hr (versus -5-5 microns/hr in paired controls) were observed. Neither the calcium antagonist diltiazem (10(-4) M), the glucocorticoid dexamethasone (10(-7) M), the glucose substitute fructose (20 mM), nor 0.5 mM adenosine and 0.3 mM reduced glutathione mitigated the edema. Lens-induced edema was 25 microns/hr in corneas bathed at pH 8.2 and decreased to 9 microns/hr at pH 7.0. In corneas without lenses, however, decreasing the pH from 7.4-7.0 caused significant swelling (P less than 0.05). The pyruvate dehydrogenase stimulant sodium dichloroacetate (3.2 mM) on the tears side ameliorated the edema, and its congener, 3.2 mM 2-chloropropionate, was less effective. These latter agents are known to relieve lactic acidosis systemically and had no significant effect on corneas without lenses. In tissues bathed with 20 mM lactate Ringer's, normal thickness was maintained in both control and PMMA-treated corneas throughout the 3-hr period. These findings suggest that the contact lens-induced edema does not involve the acute cytotoxic mechanisms seen in severe tissue ischemia or hypoxia. The edema appears to result in part from acidosis but mainly from stromal lactate accumulation.

Animals↗

PubMed1990

Long-term storage of frozen lenticules for cryorefractive surgery.

We studied freezing rates, cryoprotectants, and storage times on keratocyte viability, using rabbit corneal buttons incubated in either KM-26, CPTES, K-Sol, or TC 199 for 30 minutes at 4 degrees C. Using a controlled freezing rate (2 degrees/min to -40 degrees C), viabilities were 69 +/- 7% for KM-26, 113 +/- 21% for CPTES, 0.1 +/- 0.08% for K-Sol, and 0 +/- 0% for TC 199. The KM-26 and CPTES were further studied in corneas stored one to 30 days at -80 or -196 degrees C; CPTES had a better cryoprotective efficacy over one, three, and seven days of -80 degrees storage, and at liquid nitrogen storage temperature (-196 degrees) over one, 14, and 30 days storage. The findings demonstrate the superiority of CPTES. It provides better viability than KM-26 under similar conditions, and may enable long-term frozen storage of lenticules for later use in cryorefractive surgeries, with minimal loss of keratocyte viability.

Animals↗

PubMed1990

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 6. Trans-6-[2-(substituted-1-naphthyl)ethyl(or ethenyl)]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones.

A variety of trans-6-[2-(substituted-1-naphthyl)ethyl(or ethenyl)]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones were prepared and, upon conversion to their 3,5-dihydroxy carboxylates, were found to have good inhibitory activity against the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-determining enzyme in cholesterogenesis. The most active compounds are 2,4,6- and 2,4,7-trichloro derivatives and would be expected to display about the same potency as the standard compactin upon resolution.

Chemical Phenomena↗

PubMed1990

Proton NMR relaxation in hydrogel contact lenses: correlation with in vivo lens dehydration data.

A study of hydrogel contact lenses was undertaken to determine whether NMR relaxation data can be used as a predictor for on-eye lens dehydration. Proton NMR relaxation times (T1 and T2), were determined for a series of contact lenses for which on-eye dehydration data were also available. NMR relaxation times were found to depend upon lens water content, but the dependence was not monotonic. T1 values varied between 100 and 800 msec, and T2 values varied between 6 and 85 msec for the lenses studied. In this study, the NMR signal and corresponding relaxation times are average values, derived both from lens water protons as well as from exchangeable polymer protons. A simple analysis of the data indicates that the mobility of these protons varies by more than a factor of 10 for the lenses studied. A test for linear correlation between NMR relaxation rate, 1/T1 and relative change in lens water mass, % delta mw gave r = -0.830 for all data, and r = 0.904 if one lens was excluded.

Contact Lenses, Hydrophilic↗

PubMed1990

Contact lens-induced edema in vitro. Ion transport and metabolic considerations.

The relationship of contact lens-induced edema to epithelial and endothelial function was determined in isolated superfused rabbit corneas. Placement of a polymethyl methacrylate (PMMA) contact lens on the cornea caused swelling rates of 15-28 microns/hr compared to 0-6 microns/hr in paired control corneas. The edema increased with temperature (P less than 0.01). PMMA-induced swelling was significant in: 1) bicarbonate-free Ringer's solution; 2) chloride-free Ringer's; 3) 0.3 mM furosemide-treated corneas; and 4) deepithelialized corneas. The swelling did not occur in corneas with silicone oil replacing the endothelium to block fluid uptake. The effluent aqueous bathing fluid from edematous corneas did not induce edema in normoxic corneas. These studies demonstrate that contact lens-induced edema depends on metabolism, involves a significant stromal contribution, and requires fluid absorption across the endothelial layer, but is not a direct result of epithelial and endothelial ion transport inhibition.

Animals↗

PubMed1990

Effects of sodium lactate on isolated rabbit corneas.

Corneal stromal lactate accumulation may result from epithelial hypoxia and contact lens wear, but the possible corneal toxicity of lactate has not been reported. Isolated superfused whole rabbit corneas were examined for thickness changes during exposure to neutral sodium lactate (NaL) or excess sodium chloride (NaCl) in Krebs-bicarbonate Ringer's solution for a 3-hr period. Placed in the tears side bath, 5 mM NaL significantly thinned corneas (swelling rates of 1 +/- 1 micron/hr in Ringer's controls vs -11 +/- 1 micron/hr in lactate-treated corneas; mean +/- SD). Excesses of 5 mM NaCl had essentially identical effects (0 +/- 1 micron/hr in controls vs -13 +/- 3 micron/hr in experimentals). When placed on the aqueous side of normal-thickness corneas, neither 20 mM NaL nor 20 mM excess NaCl affected corneal thickness, but both solutions stimulated endothelium-mediated deswelling in preswollen deepithelialized corneas. When "loaded" into the stroma of deepithelialized corneas, Ringer containing 20 mM lactate caused more swelling than Ringer's alone (491 +/- 18 microns in controls vs 558 +/- 20 microns in loaded corneas; mean +/- SEM). A similar swelling occurred when 20 mM excess NaCl was loaded into the stroma (483 +/- 15 vs 565 +/- 20 microns in controls and loaded corneas, respectively), due to fluid uptake into the hypertonic stroma across the endothelium from the aqueous side (Ringer's) bath. Corneas both loaded and superfused with either NaL or excess NaCl swelled and subsequently deswelled similar to controls swollen and superfused in Ringer's.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Mechanism of inhibition of net ion transport across frog corneal epithelium by calcium channel antagonists.

In the isolated bullfrog cornea, three calcium channel antagonists had dose-dependent inhibitory effects on the Cl-originated short-circuit current (SCC). Their order of decreasing potency was bepridil, verapamil and diltiazem. One millimolar diltiazem inhibited the SCC by 98% and subsequent incubation with the calcium ionophore A23187 had no restorative effect. Increasing the bathing solution Ca concentration from 0.05 to 15 mM, however, decreased diltiazem's inhibitory efficacy. This antagonist depolarized the intracellular potential difference Vsc from -54 to -18 mV (tear:reference) and the voltage divider ratio FRo decreased from 0.58 to 0.30, suggesting an increase in basolateral membrane electrical resistance. Additional indication of a basolateral membrane effect by the drug was that preincubation with 10(-5) M amphotericin B in Cl-free Ringer's did not eliminate the inhibitory effect of the drug on the Na- and K-elicited SCC. In the absence of amphotericin B in Cl-free Ringer's (SCC = 0), 1 X 10(-3) M diltiazem depolarized the Vsc from -78 to -9 mV suggesting that the increase in basolateral membrane resistance was due to K channel blockade. Diltiazem (1 X 10(-3) M) significantly decreased cyclic AMP content; however, isoproterenol in the presence of the drug increased cyclic AMP fourfold without having any restorative effect on the inhibited SCC. Therefore, the inhibition of the Cl-originated SCC resulting from an increase in basolateral membrane K resistance is not caused by a decline in cyclic AMP content.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

PubMed1979

A new platelet aggregation inhibitor which possesses hypolipemic and uricosuric properties, 2-[3-(2-thiazolylthio)phenyl]propionic acid (TPA).

In vitro, 2-[3-(2-thiazolylthio)phenyl]propionic acid (TPA) at plasma concentrations ranging from 0.02 to 1.0 microgram/ml prevents aggregation of human platelets induced by various aggregating agents. Oral administration of TPA to guinea pigs inhibits platelet aggregation; the estimated dose to reduce aggregation by 50% is 0.3 mg/kg. TPA protects rabbits against arachidonate-induced thromboembolic death (50% protection at 0.79 mg/kg i.p.). TPA is a potent hypotriglyceridemic agent in rats when present in the diet in concentrations as low as 0.003%. In chimpanzees, TPA is uricosuric at oral doses of 0.625 and 2.5 mg/kg. This rare combination of pharmacological properties suggests that TPA is a potentially useful antithrombotic agent.

Adenosine Diphosphate↗

PubMed1977