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Biomedical subjects

I A Menon

Publications and source records attributed to I A Menon.

At least 37 records · Page 2Linked to original sources
PubMed1989

Nature of the oxygen species generated by xanthine oxidase involved in secretory histamine release from mast cells.

The present studies were carried out to characterize the nature of reactive oxygen species generated by the xanthine-xanthine oxidase system involved in the release of histamine by noncytotoxic and cytotoxic mechanisms. To distinguish secretory release from lytic release, mast cells were loaded with 51Cr and the release of 51Cr into the incubation medium was used as a measure of cell lysis. The secretory release of histamine was not inhibited by superoxide dismutase or catalase alone. However, together these agents inhibited the release. This suggests that the combination of superoxide and hydrogen peroxide can evoke secretory release. The lytic release of histamine, as monitored by concomitant release of 51Cr from mast cells at higher concentration of xanthine oxidase or longer periods of incubation, seems to be related to hydrogen peroxide production since catalase inhibited the cell lysis. Since it has been reported that exogenously added hydrogen peroxide at concentrations below 10 mM did not induce cell lysis, the lytic release, although hydrogen peroxide dependent, may not be due to its direct effect on the cell surface. The cell lysis observed in the xanthine-xanthine oxidase system seems to be brought about by a complex mechanism involving the interactions of hydrogen peroxide and superoxide with cellular components. These studies indicate that the beneficial effects of superoxide dismutase seen in biological systems may partly be due to inhibition of the secretory processes stimulated by superoxide.

Animals↗
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↗
PubMed1988

A paramagnetic agent causing ochronotic arthropathy.

Magnetic resonance imaging (MRI) identified a paramagnetic substance in the hyaline cartilage of the hips and knees in a patient with ochronosis. Chemical studies characterized the paramagnetic agent as melanin. The free radicals contained in melanin were shown to initiate cytotoxicity. The loss of cartilage in ochronotic arthropathy now can be explained at the electron level using the superoxide theory of oxygen toxicity. Inappropriate metabolism of oxygen also may explain early cartilage degeneration in hemochromatosis, hemosiderosis, and Wilson's disease.

Cartilage, Articular↗
PubMed1988

Ultrastructural changes produced in Ehrlich ascites carcinoma cells by ultraviolet-visible radiation in the presence of melanins.

Irradiation of Ehrlich ascites carcinoma (EAC) cells in the presence of pheomelanin, i.e., red hair melanin (RHM), has been reported to produce extensive cell lysis. Irradiation in the presence of eumelanin, i.e., black hair melanin (BHM), or irradiation in the absence of either type of melanin did not produce this effect. We observed that RHM particles penetrated the cell membrane without apparent structural damage to the cell or the cell membrane. Irradiation of the cells in the absence of melanin did not produce any changes in the ultrastructure of the cells. Incubation of the cells in the dark in the presence of RHM produced only minor structural, mainly cytoplasmic changes. Irradiation of the cells in the presence of RHM produced extensive ultrastructural changes prior to complete cell lysis; these changes were more severe than the effects of incubation of the cells in the dark in the presence of RHM. When the cells incubated in the dark or irradiated in the presence of latex particles or either one of the eumelanins particles, viz. BHM or synthetic dopa melanin, these particles did not penetrate into the cells or produce any ultrastructural changes. These particles were in fact not even ingested by the cells.

Animals↗
PubMed1988

Phototoxicity of chlorpromazine on retinal pigment epithelial cells.

As it is known that chlorpromazine (CPZ) can bind to melanins as well as cause ocular phototoxicity, we investigated the cytotoxic effects of UV-visible irradiation of melanotic and amelanotic retinal pigment epithelial (RPE) cells in the presence of CPZ. At low concentrations (5 micrograms/ml) of CPZ a photosensitization reaction took place which lysed the cells as measured by the release of 51Cr from cells labelled with chromium. At concentrations of CPZ less than 5 micrograms/ml, no significant cell lysis occurred when the cells were incubated at 37 degrees C in the dark. As the concentration of CPZ was increased to 25 micrograms/ml or more, high percentages of cells were lysed. When the melanotic RPE cells were exposed to different concentrations of CPZ and grown in culture, the cell growth (multiplication) diminished drastically with low concentrations (less than 2 micrograms/ml CPZ). Vitamin E decreased the cell lysis both in the dark and upon irradiation. Oxygen radical scavengers such as glutathione, B-carotene, mannitol, D-penicillamine as well as superoxide dismutase and catalase did not decrease cell lysis. The phototoxic effects of CPZ was found not to be due to stable photoproducts formed during irradiation of CPZ.

Animals↗
PubMed1987

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↗
PubMed1986

Reaction of superoxide anions with melanins: electron spin resonance and spin trapping studies.

Scavenging of superoxide radicals by melanin is a possible factor in the photoprotection afforded by melanin pigments. The reaction between superoxide anions and melanins has been studied by electron spin resonance and spin trapping methods. It was found that superoxide anions react to produce melanin free radicals in a reaction inhibited by superoxide dismutase but not by catalase. The rate of radical formation depends on the concentration of melanin and superoxide, the pH of the medium and the presence of diamagnetic metal ions. The melanin pigment competes with the enzyme superoxide dismutase for removal of superoxide radicals. It was found that the xanthine-xanthine oxidase system is not suitable for studying the reaction of superoxide with melanin, as the enzymatic activity of xanthine oxidase is considerably inhibited by melanin.

Cations, Divalent↗
PubMed1986

Effects of melanin-induced free radicals on the isolated rat peritoneal mast cells.

Pheomelanin from human red hair (RHM) produces considerably more cellular damage in Ehrlich ascites carcinoma cells when subjected to radiations of wavelength 320-700 nm than eumelanin from black hair (BHM). Irradiation of RHM generated large amounts of superoxide while BHM did not produce detectable amounts of superoxide. The present investigations describe the effects of irradiation of mast cells in the presence of various natural and synthetic melanins. Irradiation of mast cells in the presence of RHM and red hair melanoprotein released large amounts of histamine while BHM and synthetic melanins prepared from dopa, cysteinyldopa, or a mixture of dopa and cysteinyldopa did not release histamine. The release of histamine at lower concentrations of RHM was not accompanied by the release of 51Cr from chromium-loaded cells, suggesting that this release was of noncytotoxic nature. On the other hand, the release of histamine at higher concentrations of RHM was due to cell lysis since both histamine and cytoplasmic marker 51Cr were released to the same extent. The release evoked by large concentration RHM was not inhibited by superoxide dismutase or catalase. This suggests that the cell lysis under these conditions was not due to H2O2 or O-2. The finding that mast cells release histamine when irradiated in the presence of RHM suggests that the immediate and late-phase reactions seen in sunburn may in part be due to the release of mediators from these cells.

Animals↗
PubMed1985

Canthaxanthin.

Canthaxanthin is used as a food-coloring agent, a photoprotective agent in certain photodermatoses, a tan-simulating agent, and a pigment to darken vitiliginous skin. This article reviews the current literature on canthaxanthin and reports the evaluation of oral canthaxanthin as an artificial pigment for the management of vitiligo. Fifty-six patients were studied, using serum canthaxanthin levels, pre- and post-treatment photographs with standard conditions, physician assessment, and patient questionnaires evaluating treatment results. Canthaxanthin was rated "very satisfactory" by 10%, "satisfactory" by 35%, and "unsatisfactory" by 54% of patients. In light-skinned individuals, self-reports were "very satisfactory" in 27%, "satisfactory" in 45%, and "unsatisfactory" in 27%. In dark-skinned individuals, the treatment was less effective. Women were happier with the results than men. Major side effects were red stools and orange palms and soles. Canthaxanthin can be taken orally, is easy to use, and can be a cosmetically acceptable therapy in selected cases of vitiligo.

Adolescent↗
PubMed1985

Role of superoxide and hydrogen peroxide in cell lysis during irradiation in vitro of Ehrlich ascitic carcinoma cells in the presence of melanin.

The reactive species involved in the cell lysis during ultraviolet irradiation of Ehrlich ascitic carcinoma cells in the presence of red hair melanin (RHM) were investigated by determining 51Cr release from labeled cells. Cysteine at 1 mM in the presence of RHM increased the cell lysis during the incubation in the dark as well as during irradiation; this lysis was enhanced by superoxide dismutase (SOD). Catalase abolished the dark reaction and inhibited the cysteine-induced increase of cell lysis during irradiation. The cell lysis by the superoxide-generating xanthine oxidase system was not significantly increased by SOD, but was significantly decreased by nitroblue tetrazolium and completely abolished by catalase. The cell lysis induced by the supernatants obtained from the suspensions of RHM either irradiated alone or with cysteine was abolished by catalase. Sediments of irradiated RHM when incubated in the dark with the cells did not release 51Cr. Irradiation of the cells in the presence of the same sediments produced lysis which was not inhibited by catalase. These studies suggest that superoxide per se is not toxic to the cells, but the H2O2 formed by dismutation of superoxide produces cell lysis either directly or by generating OH through Fenton-type reactions. A large part of the cell lysis seen during irradiation of cells in the presence of RHM is not due to H2O2, but may possibly be due to the melanin free radicals formed during irradiation.

Animals↗