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Biomedical subjects

M Avaria

Publications and source records attributed to M Avaria.

18 recordsLinked to original sources

Myotonic dystrophy: relative sensitivity of symptoms signs and abnormal investigations.

Twenty-five symptoms, signs, and abnormal investigations were looked for in 20 patients with clinically-definite myotonic dystrophy. Weakness of facial muscles, neck flexors, and arm external rotators was found in all patients (sensitivity = 100%). Arm external rotation has not been reported as a frequently involved muscle in previous clinical studies on myotonic dystrophy. Careful examination of muscle strength may therefore predict which patients may or may not carry the abnormal gene for myotonic dystrophy.

Adolescent↗

Continuous flow contact lens delivery of gentamicin to rabbit cornea and aqueous humor.

The Morgan Therapeutic Lens (MTL) was investigated as a continuous corneal perfusion system in New Zealand white rabbits. Gentamicin concentration in the cornea and aqueous humor delivered by the MTL was compared to gentamicin drops (13.6 mg/ml) administered every 15 or 30 minutes. Gentamicin (1 mg/ml) or 5 mg/ml was perfused at 10 ml/hr for up to 4.0 hours. At each time interval of 0.5, 1, 2 and 4 hours, homogenized corneas and aqueous humour were assayed for gentamicin concentrations. The highest aqueous humour gentamicin concentrations of 57.99 +/- 12.86 micrograms/ml were significantly higher with the MTL and 5 mg/ml of gentamicin compared with the MTL and 1 mg/ml of gentamicin or than drops applied every 30 minutes, but not significantly different than drops every 15 minutes. Highest corneal concentrations of gentamicin of 496.04 +/- 101.16 micrograms/gm cornea were significantly higher with MTL and 5 mg/ml of gentamicin compared with the MTL and 1 mg/ml gentamicin or than drops applied every 30 minutes, but not significantly different than drops every 15 minutes. All mean gentamicin concentrations attained via the MTL exceeded the mean inhibitory concentration for most sensitive bacterial species. The MTL is a reliable drug delivery system with distinct advantages, and may be a useful therapeutic modality in the ocular delivery of gentamicin and other drugs.

Animals↗

Quantitative determination of the melanin contents in ocular tissues from human blue and brown eyes.

This paper deals with our findings on the quantities of melanin in the tissues from blue and brown eyes. The amount of melanin in the iris, ciliary body and retinal pigment epithelium-choroid was separately determined. The results are expressed as the amount of melanin in mg tissue as well as the amount of melanin in the whole tissue. The results showed that there was no statistically significant difference between the melanin content of the iris in blue and brown eyes. However the ciliary body and retinal pigment epithelium-choroid from brown eyes had more melanin than the corresponding tissues from blue eyes. Blue and brown eyes with higher colour intensity had more melanin than the corresponding eyes with lesser intensity of colour. It is suggested that the differences between brown and blue eyes in their melanin content may have relevance to the pharmacokinetics of drugs that bind to melanin. This would mean that the larger amounts of melanin would decrease the initial levels of the drugs and would increase the drug levels after prolonged periods.

Choroid↗

Bio-effects of extremely low frequency electromagnetic fields (60 Hz.) on the healing of corneal epithelial wound: an in vitro study.

The organ cultures of standardized epithelial wound of rabbit cornea, were exposed to electric and magnetic fields components of the extremely low frequency (60 Hz) sinusoidal electromagnetic field, separately or in combination. The electric field was applied as a pure electric current via an agar-salt bridge, and the magnetic field component was applied as a pure polarized magnetic field by means of a pair of energized coils in a Helmholtz configuration. The two field components were at right angles to each other and in phase (phi = 0 degrees) when applied in combination. Their vectors or planes of polarization were parallel to the surface of the culture dish. The three exposure combinations used were: a) electric current density of 0.19 V/m (30 microA/cm2) and/or magnetic fields strength of 1.0 Gauss. (low intensity) b) electric current density of 0.31 V/m (50 microA/cm2) and/or magnetic fields strength of 1.5 Gauss. (medium intensity) c) electric current density of 0.57 V/m (90 microA/cm2) and/or magnetic fields strength of 2.5 Gauss. (high intensity). After 2 days of exposure the incorporation of radiolabelled thymidine into DNA of the regenerating epithelial cells was determined. Results showed thymidine incorporation (adjusted by regression for differences in the levels of DNA in corneal wound) (DNA*) depended upon the electromagnetic field strength. The only significant effect on this outcome, was an interaction effect between the electric (E) and magnetic (M) fields employed. The size and direction of this interaction depended strongly on the maximum field strengths. At the lowest level DNA* was significantly lower when both fields were present than would be expected from the effects of either field alone. At the highest level, DNA* was significantly higher. There were no significant effects for medium field strengths.

Animals↗

Pharmacological studies on the in vivo cataractogenicity of acetaminophen in mice and rabbits.

Acetaminophen can be enzymatically bioactivated, which may play a role in cataractogenesis. This study evaluated the relation of dose, sex, plasma drug concentration, cytochromes P-450 (P-450 and P-448) induction, and hepatocellular toxicity to cataractogenic susceptibility in inbred mice and rabbits. C57BL/6 or DBA/2 mice, which respectively are genetically responsive and nonresponsive to P-448 induction, were treated with acetaminophen, 300 to 1000 mg/kg intraperitoneally (ip), following pretreatment with the P-448 inducer 3-methylcholanthrene (3-MC). Bilateral cataracts developed, independent of sex, in 83% of C57BL/6 mice within 4 hr of acetaminophen administration, compared with 7% of DBA/2 mice. A dose-response relation for cataractogenesis was evident in C57BL/6 mice using doses of 300 and 400 mg/kg, with the higher dose producing similar plasma acetaminophen concentrations but twofold higher glucuronide concentrations. Both strains had increased plasma concentrations of glutamic-pyruvic transaminase (GPT). New Zealand white or Chinchilla pigmented rabbits were treated with single or multiple doses of acetaminophen, 500 to 1500 mg/kg/day ip, following pretreatment with a cytochromes P-450 inducer: phenobarbital, 3-MC, or beta-naphthoflavone. Acetaminophen given chronically caused lenticular opacities within 1 week in 19 of 20 rabbits pretreated with P-450 inducers, regardless of pigmentation, but not in animals without prior P-450 induction. No opacities were observed after a single dose of acetaminophen, even with P-450 induction. There was no increase in plasma GPT in rabbits with any treatment. Over 85% of acetaminophen was recovered in urine as a glucuronide conjugate, and the rest as acetaminophen or conjugates with sulfate, cysteine, or N-acetylcysteine. Susceptibility to acetaminophen cataractogenesis can be genetically predetermined and may involve enzymatic bioactivation. possibly independent of hepatic biotransformation and toxicity.

Acetaminophen↗

Is there any difference in the photobiological properties of melanins isolated from human blue and brown eyes?

Investigations were carried out to determine whether the melanin present in the blue and brown eyes were eumelanin, the melanin present in black hair and dark skin, or pheomelanin, the melanin present in red hair and the skin of people with red hair. Our results showed that UV-visible irradiation of blue or brown eye melanin did not produce any superoxide. Irradiation of 51Cr-labelled Ehrlich ascites carcinoma cells in the presence of blue or brown eye melanin did not produce significant cell lysis. The electron spin resonance (ESR) signals of blue and brown eye melanins were very similar to those of eumelanin. Comparison of these findings with our previous results indicated that the blue and brown eye melanins are essentially eumelanin. The ESR signals further suggested that in the case of both blue and brown eye melanins the iris, ciliary body, choroid, and retinal pigment epithelium did not differ.

Aged↗

Ocular distribution of methyprylon after intravenous injection and transfer of the drug to recipient eye via corneal graft.

The purpose of the study was to determine chronologically the ocular distribution of methyprylon (Noludar) after a single intravenous injection (45 mg/kg) to rabbits, if the drug can be transferred from a donor treated with the drug to the recipient's eye via an allogeneic corneal graft, and the effect of methyprylon on corneal cell growth and protein synthesis. Gas chromatographic techniques showed that the drug was present in all the tissues and fluids of the eye from 0.5 to 18 hours after the injection. Postoperatively, the cornea and some of the other ocular tissues of the recipient contained methyprylon at least 24 hours after transplantation. Clinically, the graft remained clear, and there was no adverse reaction in the recipient eye for an observation period of 24 hours. Tissue culture studies showed that about 10 times more methyprylon than was found in the donor cornea was necessary to produce a cytotoxic reaction on the corneal cells in terms of cellular growth rate and protein synthesis. Our animal experiments and cytotoxicity tests suggest that corneas of donors treated with a high dose of methyprylon would be suitable for use as grafts.

Animals↗

Should corneas from donors receiving a high dose of salicylate be used as grafts: an animal experimentation.

Rabbits were injected intravenously with a single dose of sodium salicylate (350 mg kg-1) in order to study the following in vivo: (i) the distribution of the drug in the various eye tissues and fluids, particularly the cornea and aqueous humour, and (ii) transfer of the drug from corneal grafts obtained from donors receiving sodium salicylate to the eye tissues of the recipient. In additional experiments, the in vitro effects of sodium salicylate on the growth and protein synthesis of corneal cells grown in tissue culture were also studied. In vivo experiments showed that the periods during which we observed the highest concentration of salicylate in the serum and in the eye tissues were within 30 min and 2 hr respectively following the injection. These experiments also showed that salicylate was transferred from the treated donor via corneal graft to the recipient's eye tissues where it could still be detected 48 hr after the operation. In vitro experiments showed that a 50% inhibition of cell growth was obtained at a concentration of about 1000 micrograms salicylate ml-1 while protein synthesis was decreased by 50% at a concentration of about 200 micrograms ml-1. A consideration of our data from the in vivo and in vitro experiments together suggests that ingestion by the donor of high concentrations of salicylate may have the potentiality of subjecting the corneal endothelial cells to cytotoxic concentrations of the drug thus jeopardizing the success rate of corneal graft operations.

Animals↗

Ocular distribution of sodium pentobarbital after injection of lethal and anesthetic doses and after transfer via corneal grafting.

The distribution of sodium pentobarbital in the eye after lethal and anesthetic doses and the possibility of the drug's transfer via corneal grafting were studied in rabbits. The drug was found in all the ocular tissues and humours following the intravenous injection of a single lethal (60 mg/kg) or anesthetic (30 mg/kg) dose, and it was still present 24 hours after the anesthetic injection. In both instances the largest quantity was found in the cornea. After grafting of corneal tissue containing pentobarbital the drug dispersed into the recipients' corneas and other ocular tissues. In-vitro studies showed that 250 micrograms of the drug per millilitre of incubation medium reduced the rate of growth of the corneal fibroblasts to 50%, and 300 micrograms/mL reduced their protein synthesis to 66%. Calculations showed that these concentrations could be reached in the cornea or the aqueous humour in vivo following either the lethal or the anesthetic injection of the drug.

Anesthesia↗

Ocular effects of water from acidic lakes: an experimental study.

The purpose of this experimental study was to determine the effects on the conjunctiva and cornea of eyes exposed to water from acidic lakes in comparison with water from lakes having a nearly neutral pH. One eye each of 190 rabbits was exposed to an experimental sample of water having a pH of 5.18, 5.04, 4.70 or 4.50. The other eye of each rabbit was simultaneously exposed to a control sample of water having a pH of 6.40 or 6.21. The water was continuously instilled for 15 minutes every day for 7 days. Observations were made daily. The two eyes of each rabbit were compared for conjunctival congestion, corneal staining with fluorescent dye, the granulocyte count and osmolarity of the tears, bacteriologic findings in conjunctival swabs, corneal cell damage, corneal thickness and ultrastructural features of the corneal epithelium. Although some of the rabbits showed a difference of reaction in the two eyes, the majority showed similar reactions to water from the acidic and nearly neutral lakes.

Animals↗

Distribution of morphine in the eye tissues and fluids of rabbits after systemic administration and after transfer via corneal grafting.

To determine whether corneas from animals receiving morphine could be used for grafting, rabbits were given a single intravenous injection of tritium-labelled morphine and killed 10 minutes later. Of the drug entering the eye, 12% was found in the cornea, 36% in the retina and optic nerve, 29% in the uveal tissues, 8% in the aqueous humour, 8% in the choroid, 4% in the vitreous humour and 2% in the lens. Another group of rabbits then received full-thickness corneal grafts from rabbits treated with morphine. The grafts contained the drug for up to 21 days after transplantation. From the graft bed the agent dispersed into the different solid ocular tissues and intraocular fluids. None of the grafts failed, and none of the recipients' eyes showed any adverse reaction. In-vitro tests showed that the amount of morphine found in the cornea and the aqueous humour of the donor did not have any significant effect on cell division or protein synthesis of the corneal cells. Higher concentrations of the drug, however, decreased both cell division and protein synthesis.

Animals↗

Distribution of penicillin in the cornea, tears and aqueous humour at various times following a single intravenous injection.

Bioassays performed by the disc diffusion technique on samples of blood, tears, aqueous humour and cornea from 30 rabbits killed 4 to 24 hours following a single intravenous injection of benzylpenicillin (40 mg/kg) showed that the penicillin content of these fluids and tissues progressively decreased with time. However, even after 24 hours the agent could be detected in the samples. The peripheral and central cornea contained similar amounts of penicillin up to 16 hours; thereafter, the peripheral cornea contained more of the agent.

Animals↗

Effects of acidic lake water on the eye.

The normal eyes of 6 men and 21 rabbits were exposed to samples of lake water, one eye to a sample of pH 4.6 and the other to a sample of pH 6.3. The men's eyes were exposed for 5 minutes on four occasions a week apart, whereas the rabbits' eyes were exposed for 15 minutes either on one occasion or once a day for 7 days. In the humans neither sample of water produced symptoms or signs of an adverse effect on the external eye tissues, apart from brief conjunctival congestion after every exposure. In the rabbits the two samples did not appear, in general, to have different effects on the ocular tissues, as judged from the osmolarity and cell count of the tears, conjunctival congestion, corneal staining with fluorescein, corneal permeability and histologic features of the cornea. In a few instances differences were observed, but their pathological significance was not apparent. These data suggest that lake water of a pH as low as 4.6 may not harm healthy eyes, however, larger and broader studies are essential.

Acids↗

Effect of hydrocortisone on the mobilisation of leucocytes in corneal wounds.

We have studied in rabbits the effect of subconjunctivally injected hydrocortisone on the polymorphonuclear leucocyte invasion of corneal wounds at different times after an injury. One group of rabbits was treated with the steroid (hydrocortisone group) and the other not (control group). After making nonpenetrating trephine incisions on the cornea we obtained cellular samples by the impression technique at a given postoperative period (2, 4, or 6 hours), and then the animal was killed. The cornea was processed for histological study of the infiltrating cells. At any postoperative period the number of polymorphonuclear leucocytes in the corneal wounds of the hydrocortisone group was significantly less than the number in the identical wounds of the control group (p less than 0.01 to 0.001).

Animals↗

Impression cytology in conjunctivitis.

A technique is described for studying the cellular response in various conjunctival disorders. A round plastic disc (Thermanox) is pressed against the patient's conjunctive, and the material adhering to the disc is stained with a modified Wright's stain (Diff-Quik) for light microscopy. This method compares favourably with the classic conjunctival scraping method. The advantages of the impression technique are that no local anesthetic is needed for abtaining conjunctival samples, it is painless and can readily be used in children, repeated samples can be taken within a short time, the staining procedure can be completed within 15 seconds, and the discs can be processed for electron microscopic studies of the cellular samples.

Adolescent↗