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Biomedical subjects

P K Basu

Publications and source records attributed to P K Basu.

At least 37 records · Page 2Linked to original sources
PubMed1990

The effects of donor age and cause of death on corneal graft survival.

The Ontario Corneal Recipient Registry followed 299 recipients of 326 corneal transplants performed between October 1985 and October 1987. This report describes the joint effects of donor age and cause of death on subsequent graft survival in these procedures up to two years after surgery. Cox regression analysis established that grafts from donors dying of injury experienced half the risk of graft failure of those from donors dying of heart disease or other natural causes (P less than 0.05). Although donor age differed substantially between these causes of death, controlling for donor age did not alter the association. There were no statistically or clinically significant differences in graft survival associated with either donor age or recipient age. These results suggest that the health of the donor and the circumstances surrounding death may influence the quality of corneal tissue, and deserve more attention and detailed study.

Actuarial Analysis↗
PubMed1990

Quantitative analysis of collagen content and amino acids in trabecular meshwork.

The purpose of this study was to compare collagen content in the TM of normal and glaucomatous eyes, and to establish whether collagen levels change with age. Collagen content was measured in 30 normal and 27 age matched glaucoma trabeculectomy specimens by the sirius red dye binding technique, and in 14 normal and 15 age matched glaucoma specimens by amino acid analysis. Both dye binding data and amino acid analysis showed no statistical difference between normal and glaucoma samples. Age had no significant effect on mean optical densities or on the collagen-specific amino acids proline, hydroxyproline, and hydroxylysine. Amino acid variability, however, was statistically different between the two groups. These results indicate that mean collagen levels in the trabecular meshwork of glaucomatous eyes do not differ from those in normal eyes.

Adult↗
PubMed1990

Potential value of collagen shields as a subconjunctival depot release system.

Collagen shields are fabricated from dissoluable porcine scleral tissue and have been used as an ocular drug delivery system. The aim of the present study was to determine the time and extent of shield absorption when implanted subconjunctivally, and the absorption and release of 5-fluorouracil in vitro. Thirty New Zealand white rabbit eyes were employed. BioCor 72 hour collagen shields were surgically implanted in the subconjunctival space. Rabbits were sacrificed at 7, 14 and 21 days after shield implantation, and the remaining shields removed. Remaining shields were measured by both dry weight and protein assay. The absorption and release of 5-FU from collagen shields was determined in vitro using tritiated 5-FU. The collagen shields were not fully absorbed for at least 14 days in the subconjunctival space. In vitro, 5-FU absorbed by the shields reached saturation levels at approximately 15 minutes. Nearly 100% of the 5-FU was released within 15 minutes. Although the time for subconjunctival shield absorption may be useful for antifibroblast drugs, the rate of 5-FU release from these shields is not optimal for enhancing bleb formation when shields are soaked in solutions of 5-FU.

Absorption↗
PubMed1989

A study on the sequence of phototoxic effects of rose bengal using retinal pigment epithelial cells in vitro.

This paper describes a study on the sequence of the phototoxic effects of rose bengal (RB), a fluorescein derivative used as a vital stain in the diagnosis of certain external ocular diseases. Bovine melanotic RPE cells were grown in culture. These cells were labeled with [51Cr] and exposed to visible light in the presence of various concentrations of RB; the leakage of [51Cr] from the cells was used as a measure of cell lysis. Exposure to light of the cells with 0.3-10 microM RB induced approximately 13 to 43% cell lysis. The lysis progressively increased when the exposure time was varied from 10 to 30 min. A relatively short period of irradiation in the presence of RB was sufficient to produce sublytic cellular injury which could subsequently lead to complete cell lysis even in the absence of the photochemical treatment. The dark reaction was time-dependent, and reached a maximum for a given irradiation period. Our results thus show that there are two different processes that could eventually lead to the cell lysis: (a) a phototoxic effect which caused a sublytic damage and (b) a dark reaction that followed.

Animals↗
PubMed1989

Binding of timolol to iris-ciliary body and melanin: an in vitro model for assessing the kinetics and efficacy of long-acting antiglaucoma drugs.

Topical beta blockers are used to treat glaucoma patients. These drugs inhibit aqueous production for prolonged periods of time. The purpose of this study was to determine whether timolol maleate (a non-specific beta blocker) binds to human iris-ciliary body (CB) melanin and to elucidate the binding characteristics of the drug to melanin. Timolol bound to bovine iris and ciliary body by two possible mechanisms. The binding kinetics indicate that the binding is probably of a nonspecific nature. There was no statistically significant differences between the melanotic tissues (CB, iris) and the nonmelanotic tissues (lens, cornea, liver, kidney) regarding the amount of timolol bound. However significantly more timolol was bound to the isolated melanins than the whole tissues. Timolol was released from the nonmelanotic tissues at a much faster rate than from the melanotic tissues. The amount of timolol bound to iris-CB from albino and pigmented rabbits showed that the amount of timolol bound to these tissues diminished in the following order: black or gray greater than brown greater than albino. It was also found that the rate of timolol release decreased in the following order: albino greater than gray greater than brown or black. Our results demonstrate the binding of beta blocker to human, bovine and rabbit iris-CB and consequent slow release of timolol from these tissues.

Adrenergic beta-Antagonists↗
PubMed1989

Ultrastructural effects of topical betoptic, betagan, and timoptic on the rabbit corneal endothelium.

Scanning and transmission electron microscopy was used to evaluate the cytotoxic effect of three commercially available beta adrenergic blockers (Betoptic 0.5%, Betagan 0.5% and Timoptic 0.5%), and preservative (benzalkonium chloride 0.01%) on rabbit corneal endothelium. Evaluation was performed on groups including intact corneas, de-epithelialized corneas, full-thickness corneal grafts with intact epithelium, and de-epithelialized corneal grafts. Both Betoptic and Betagan produced minor damage to endothelial microvilli in the intact epithelial group. The de-epithelialized and the grafted-cornea groups had less damage induced by Betoptic than Betagan. Timoptic produced more endothelial damage than Betoptic and Betagan in all groups. Benzalkonium chloride produced minimal endothelial damage. Results indicate that Betoptic produces less endothelial toxicity than the two non-specific beta blockers when corneal epithelium is damaged and after penetrating keratoplasty.

Administration, Topical↗
PubMed1989

The toxic effects of pilocarpine gel and drops on rabbit cornea.

Pilocarpine drops and gel were applied daily for 3 months to rabbit cornea to determine their cytotoxic effects. The corneas were examined clinically with slit lamp biomicroscopy and histologically with scanning and transmission electron microscopy. The gel-treated corneas developed edema and desquamation of the superficial epithelial layers. Vacuoles, swollen mitochondria and amorphous deposits were detected in the basal epithelial layers. The drop-treated corneas developed endothelial cell damage characterised by cytoplasmic vacuoles, swelling and degeneration of the intracellular organelles. The study confirms the clinical impression that pilocarpine gel can produce anterior corneal damage. The toxic effect of pilocarpine gel on the corneal endothelium was much less than the effect produced with pilocarpine drops.

Administration, Topical↗
PubMed1989

High resolution scanning electron microscopy of rabbit corneal endothelium to show effects of UV-visible irradiation in the presence of chlorpromazine.

The ultrastructure of rabbit cornea endothelial cells was examined by scanning electron microscopy (SEM) in freeze-cleaved corneas using a Hitachi S-570 scanning electron microscope in the high resolution mode (HRSEM). In order to study phototoxic effects in vitro, rabbit corneas (experimental) were cultured as organ culture in the presence of 5 micrograms/ml chlorpromazine (CPZ) and irradiated. For comparison, control 1 corneas were not irradiated but incubated in the dark without CPZ in the medium; control 2 corneas were also kept in the dark but in the presence of CPZ; control 3 corneas were irradiated with no CPZ in the medium. Cellular damage was not seen in the three types of control corneas, but in the experimental corneas the endothelial cells showed extensive disruption of the cell membrane and some deterioration of the intracellular components. Our study confirmed that HRSEM is a satisfactory new technique for visualizing damage of the intracellular organelles of corneal endothelium.

Animals↗
PubMed1989

Binding of chlorpromazine to cultured retinal pigment epithelial cells loaded with melanin.

The accumulation of chlorpromazine (CPZ) in cultured bovine amelanotic retinal pigment epithelial (RPE) cells artificially loaded with melanin was investigated. The melanin was isolated from human eye bank eyes. Suspensions of the melanin were added to the RPE cells and incubated for 3 hrs. The cells ingested the melanin which was dispersed in the cytoplasm of the cells. They were not adhering to the cell membrane. The melanin-loaded cells grew in culture, although their rate of growth was slower than that of the control RPE cells not loaded with melanin. When the melanin-loaded cells were treated with CPZ, these cells accumulated a greater amount of CPZ than the control cells. A greater amount of CPZ was released from the melanin-loaded cells than from the control cells. The results suggest that some drugs or chemicals such as CPZ could accumulate in vivo in larger quantities and for longer periods in melanotic cells than in nonmelanotic cells. These compounds may subsequently be released into the extracellular fluid, thus affecting the neighbouring cells. This phenomenon may play an important role in the activities of these drugs in the melanotic cells and in the cells adjacent to the melanotic cells. These results suggested that cultured cells loaded with melanin could be used as a suitable model for studying the mechanisms of binding of drugs to intracellular melanin, and of their subsequent release outside the cells.

Animals↗
PubMed1989

Phototoxic effects of 8-methoxypsoralen on rabbit corneal endothelium.

The phototoxic effects of 8-methoxypsoralen (8-MOP) were investigated using the rabbit corneal endothelium in organ culture. The corneas were divided into four groups: (a) irradiated with a mercury vapor lamp (emitting UVA and visible radiation) in the presence of 8-MOP (experimental), (b) irradiated without 8-MOP (control A), (c) incubated with 8-MOP (control B) and (d) incubated without 8-MOP (control C). Specular and light microscopic examination showed that the experimental corneas had greater cellular damage compared to the control corneas. The effects of 8-MOP were restricted to certain localized areas of the cornea. However there was no significant difference in the amounts of 51Cr released from the labelled experimental and control corneas. These results show phototoxic damage of the corneal endothelial cells.

Animals↗
PubMed1989

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↗
PubMed1989

Cytotoxicity of gentamicin on corneal endothelium stored in vitro.

Since corneas are preserved in storage media containing gentamicin, the risk of gentamicin toxicity could increase with the increase in the storage time as well as with the increase in the concentration. We wished to determine the safety level of gentamicin on the corneal endothelium in terms of its concentration as a function of the storage time. One cornea (experimental) of a rabbit was stored in chondroitin sulfate medium (CSM) containing 0.5 mg/ml or 1 mg/ml of gentamicin, and the other cornea (control) was kept in CSM containing 0.1 mg/ml of gentamicin. Both corneas were stored up to 14 days at 4 degrees C. After storage, each corneal endothelium was studied by specular microscopy, light microscopy (following staining with trypan blue and alizarin red) and transmission electronmicroscopy. In comparison with the control corneas, the experimental corneas showed progressively greater amounts of endothelial cell damage, as the concentration of gentamicin or the storage time was increased. Our morphological study indicates that the presently recommended concentration of gentamicin (0.1 mg/ml) is not cytotoxic to the corneal endothelium provided the time of storage does not exceed 7 days.

Animals↗
PubMed1989

Cataractogenicity and bioactivation of naphthalene derivatives in lens culture and in vivo.

The cataractogenicity of naphthalene derivatives was investigated in a lens culture system that included the lens with an intact capsule and epithelium. The in vivo cataractogenicity of naphthalene, 1000 or 2000 mg/kg ip, also was evaluated in New Zealand white and Chinchilla pigmented rabbits. A dose-related brunescence was observed in lenses incubated with 1,4-naphthoquinone in concentrations from 31.6 to 316 microM. With 316 microM naphthoquinone, lenses were totally opaque within 24 hr. No lenticular opacities were observed with 1-naphthol or 2-naphthol in incubations lasting up to 96 hr. The bioactivation of naphthalene derivatives to reactive free radical intermediates by lenses in organ culture was investigated by electron spin resonance spectrometry (ESR) using the spin trap alpha-phenyl-N-t-butylnitrone (PBN). Lenses were incubated with 316 microM naphthoquinone and 100 mM PBN for 0.25, 4 or 7 hr. A spin trapped radical product with unresolved peaks was observed with 0.25 and 7 hr incubation. No radicals were detected in the 4 hr incubation, nor in control cultures lacking either the lens, naphthoquinone or PBN. In the in vivo studies, naphthalene was cataractogenic in both albino and pigmented rabbits. The in vitro results indicate that naphthoquinone can be bioactivated by rabbit lens to a reactive free radical intermediate, which may contribute to cataractogenicity.

Animals↗
PubMed1989

Donor eyes. A comparison of characteristics and outcomes for Eye Bank and local tissue.

The Corneal Recipient Registry was begun in 1985 to collect information on all recipients of corneal grafts in the province of Ontario, Canada, and on the donors providing tissue. While most of the tissue is handled by the Eye Bank of Canada (Ontario Division), ophthalmologists in centers away from the Eye Bank often use local tissue when it is available. Comparison of the donor characteristics of local tissue with that obtained through the Eye Bank revealed that local donors were 9-10 years younger (p less than 0.01), their times to enucleation were an hour less (p less than 0.02), and they were much more likely to be the victims of trauma than the donors of Eye Bank eyes. Prognosis of the graft, assessed using life table methods, suggested that success of local eyes was 89% after 6 months, compared with 80% for Eye Bank eyes in the same period, but this was not a significant difference (p greater than 0.05). While the Eye Bank is a more common source of tissue, eyes obtained locally are more likely to represent the "ideal" tissue for many corneal surgeons.

Adult↗
PubMed1989

Public attitudes toward donation of body parts, particularly the eye.

A survey of 595 metropolitan Toronto residents aged 16 years or older was done during 1986-87 to assess their interest in organ and tissue donation in general and their willingness to donate eyes in particular. Subjects were selected at random from the telephone directory and were interviewed on the telephone with a prepared questionnaire. Most of the respondents were aware of the value and types of organ and tissue transplantation. Although 63% expressed a willingness to donate body parts, only 37% had signed the organ donation portion of their driver's licence or an organ donor card. The respondents who were unwilling to donate body parts expressed certain deep-rooted anxieties and fears. More public education is needed to allay the fears and misunderstandings that remain in the minds of many potential donors.

Attitude↗
PubMed1988

Metabolic evidence for the involvement of enzymatic bioactivation in the cataractogenicity of acetaminophen in genetically susceptible (C57BL/6) and resistant (DBA/2) murine strains.

Acetaminophen has been shown to be cataractogenic in mice and rabbits. C57BL/6 and DBA/2 mice respectively are genetically susceptible and resistant to the induction of cytochrome P-448 by 3-methylcholanthrene (3-MC). This isoenzyme is thought to bioactivate acetaminophen to a toxic reactive intermediate. These two murine strains also are correspondingly susceptible and resistant to acetaminophen cataractogenesis. To evaluate the potential role of enzymatic bioactivation as a determinant of acetaminophen cataractogenesis, C57BL/6 and DBA/2 mice were treated with acetaminophen, 300 or 400 mg/kg intraperitoneally (ip), with or without pretreatment 48 hr earlier using 3-MC, 200 mg/kg ip. Lenticular cataracts were evaluated using the unaided eye and a slit lamp, and hepatotoxicity was evaluated by determination of peak plasma concentration of alanine aminotransferase (ALT). Plasma concentrations of acetaminophen and metabolites, particularly the glutathione (GSH)-derived conjugates (cysteine and mercapturic acid) reflecting enzymatic bioactivation, were measured by high-performance liquid chromatography. Cataracts developed only in C57BL/6 mice pretreated with 3-MC, occurring in 1 of 5 and 5 of 5 animals treated respectively with 300 and 400 mg/kg of acetaminophen. Comparing these two groups of induced C57BL/6 mice, production of the cysteine conjugate of acetaminophen was 2.5-fold higher with the 400 mg/kg dose of acetaminophen (p less than 0.05). Compared to their respective dose-matched, noninduced controls, cysteine conjugate production in the 300 and 400 mg/kg dose groups of induced C57BL/6 mice respectively was 3-fold and 4-fold higher (p less than 0.05). No DBA/2 mice developed cataracts. No mercapturic acid conjugate was detectable in the plasma of DBA/2 mice, and production of the cysteine conjugate was not altered in this strain by increasing the dose of acetaminophen or by pretreatment with 3-MC. The mean peak plasma concentration of the cysteine conjugate, reflecting acetaminophen bioactivation, was 5-fold higher in animals developing cataracts compared with those without cataracts (p less than 0.001). Plasma concentrations of unmetabolized acetaminophen were similar in all groups and unrelated to the development of cataracts. All mice of both strains pretreated with 3-MC showed evidence of hepatotoxicity, indicating a dissociation between hepatotoxic and cataractogenic susceptibility.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetaminophen↗
PubMed1988

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↗