Biomedical subjects

D Abran

Publications and source records attributed to D Abran.

27 records · Page 2Linked to original sources

PubMed1994

Melatonin activity rhythms in eyes and cerebral ganglia of Aplysia californica.

In this study, we used a sensitive and specific radioimmunoassay to detect a substance which appears to be melatonin, an acetylation and methylation product of serotonin, in the eyes and central nervous system of the opisthobranch mollusc Aplysia californica. This identification was confirmed in the eyes by HPLC with fluorimetric detection. Melatonin activity was high in the eyes during the day and in the cerebral ganglia during the night. Only small amounts of melatonin were present at midday or midnight in the pedal ganglia. A single 1-hr exposure to light in the middle of the dark phase resulted in a sharp increase of melatonin in the eyes, whereas no such activity was detectable in cerebral and pedal ganglia. Eyes maintained in culture exhibited a diurnal rhythm of released melatonin activity over a 3-day period. These results suggest that melatonin is produced in A. californica in a rhythmic pattern different from that associated with pineal melatonin production in vertebrates.

Animals↗

PubMed1994

Reduced responses of retinal vessels of the newborn pig to prostaglandins but not to thromboxane.

The upper blood pressure limit of retinal blood flow autoregulation is lower in the newborn than in the adult; this suggests an insufficient vasoconstrictor response in the newborn when perfusion pressure is increased. Because prostaglandins (PGs) have an important role in autoregulation of retinal blood flow, we compared the effects of PGE2, PGF2 alpha, carbacyclin (PGI2 analogue), and U46619 (thromboxane analogue), as well as that of agonists for the three different PGE2 receptor subtypes, 17-phenyl trinor PGE2 (EP1), butaprost (EP2), and M&B 28,767 (EP3), on the retinal vasculature of newborn and adult pigs, using isolated eyecup preparations. PGF2 alpha and PGE2 caused a markedly greater constriction of retinal arteries and veins of the adult than of the newborn animals. Further analysis of the response to PGE2, using receptor subtype agonists, revealed that the EP1 receptor agonist, 17-phenyl trinor PGE2, and the EP3 receptor agonist, M&B 28,767, caused a significant constriction of adult arteries and veins but produced minimal effects on newborn vessels; the EP2 receptor agonist, butaprost, caused a small and comparable dilation of newborn and adult arteries and veins. The PGI2 analogue, carbacyclin, caused a greater dilation of the adult than of the newborn arteries, but produced comparable dilation of veins from both newborn and adult animals. In contrast to the effects of PGF2 alpha and PGE2, the thromboxane analogue, U46619, as well as the alpha 1-adrenoceptor agonist, phenylephrine, significantly constricted newborn arteries and veins, and this effect was comparable with that observed on retinal vessels of the adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Free radicals in retinal and choroidal blood flow autoregulation in the piglet: interaction with prostaglandins.

PURPOSE: To study the role of free radicals in autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) and the contribution of the cyclooxygenase pathway in free radical formation during blood pressure changes in 1- to 3-day-old pigs. METHODS: Blood pressure was adjusted by inflating balloon-tipped catheters placed at the aortic isthmus and the aortic root to induce hypertension and hypotension, respectively. Blood flow was measured using the microsphere technique. Also, the effects of peroxides on retinal artery diameter were studied on eyecup preparations using time-frame photography processed by digital imaging. RESULTS: Blood gases and intraocular pressure (13 +/- 1 mm Hg) remained stable throughout the experiments. In control animals, RBF was constant only between 30 and 75 mm Hg of ocular perfusion pressure and ChBF increased as a function of ocular perfusion pressure (tau = 0.58, P < 0.01). Inhibition of peroxidation with the free radical scavenger 21-aminosteroid U74389F (2.5 mg/kg) widened the range of RBF and ChBF autoregulation (ocular perfusion pressure from 30 to 131 mm Hg). Hypertension caused an increase in the products of peroxidation, malondialdehyde, and hydroperoxides, as well as in prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in the retina and choroid of control animals; these changes were inhibited by the free radical scavengers U74389F (2.5 mg/kg) and high-dose allopurinol (140 mg/kg) as well as by the cyclooxygenase inhibitors ibuprofen (40 mg/kg) and indomethacin (5 mg/kg). In isolated eyecup preparations, H2O2 and cumene hydroperoxide dilated retinal vessels, and this effect was completely blocked by indomethacin. CONCLUSIONS: These findings indicate that free radicals play a major role in setting the upper limit of RBF and ChBF autoregulation of the newborn animal. In addition, there exists a positive feedback interaction between free radicals and cyclooxygenase activity in ocular tissues, such that during hypertension the cyclooxygenase pathway is an important producer of free radicals and in turn is also activated by them.

Animals↗

PubMed1993

Prevention of postasphyxial increase in lipid peroxides and retinal function deterioration in the newborn pig by inhibition of cyclooxygenase activity and free radical generation.

Free radicals have been implicated in the development of injury to the immature retina. Asphyxia increases free radicals as well as prostaglandins (PG) in neural tissues. We assessed whether in the retina the cyclooxygenase pathway contributes to free radical formation after oxidative insults such as asphyxia, which in turn disrupts retinal function. Newborn pigs were treated with either saline, ibuprofen (194 mumol/kg i.v.), or allopurinol (1 mmol/kg i.v.), and retinal malondialdehyde (MDA), hydroperoxides, PGE2 and PGF2 alpha levels, and the amplitudes and implicit times of the a- and b-waves of the full-field electroretinogram were measured before and 1 h after a 5-min period of asphyxia. In saline-treated animals, asphyxia caused a marked increase (p < 0.01) in MDA, hydroperoxides, PGE2, and PGF2 alpha concentrations in the retina. This was associated with a significant decrease (p < 0.01) in the b-wave amplitude measured under scotopic and photopic conditions and an increase in the b-wave implicit times. Ibuprofen and another cyclooxygenase inhibitor, indomethacin (28 mumol/kg i.v.), decreased PGE2 and PGF2 alpha levels and prevented the increase in MDA and hydroperoxides after asphyxia. Allopurinol maintained low concentrations of MDA and hydroperoxides after asphyxia. Both ibuprofen and allopurinol prevented the postasphyxial changes in the b-wave amplitude and diminished the delay in implicit time observed after asphyxia in saline-treated pigs. Our findings suggest that in the retina after asphyxia free radicals appear to originate primarily from the cyclooxygenase pathway and contribute to the deterioration in retinal electrophysiologic function of the newborn animal. Cyclooxygenase inhibitors, like free radical scavengers, may protect retinal function from deteriorating after oxidative stresses.

Allopurinol↗

PubMed1993

Fewer PGE2 and PGF2 alpha receptors in brain synaptosomes of newborn than of adult pigs.

PGE2 and PGF2 alpha decrease cerebral metabolism in the adult but increase it in the newborn. The present study was done using synaptosomes from newborn and adult pigs to find out whether these diverse cerebral effects of prostanoids are a consequence of newborn synaptosomes containing fewer or no EP2 receptors for PGE2 (mediating cAMP increase and in turn cerebral metabolism decrease) and PGF2 alpha receptors [mediating IP3 (inositol 1,4,5-triphosphate) increase and in turn cerebral metabolism decrease]. It was found that maximum binding values (fmol/mg protein) of [3H]PGE2 and [3H]PGF2 alpha were, respectively, only 11.6 +/- 0.8 and 8.6 +/- 1.4 on newborn synaptosomes compared with 41.8 +/- 1.8 and 31.2 +/- 4.8 on adult tissues. EP1 receptors were virtually absent in newborn and adult preparations. Practically all the PGE2 receptors on newborn synaptosomes were EP3 subtype, whereas adult brain synaptosomes contained both EP2 and EP3 subtypes; this was indicated by the ability of M&B 28,767, a specific EP3 receptor agonist, to cause 100% displacement of [3H]PGE2 binding to synaptosomes of the newborn but only 51% in the case of the adult. Also, PGE2, 11-deoxy PGE1 (a nonselective EP2 and EP3 agonist) and M&B 28,767 (an EP3 agonist) caused comparable decreases in cAMP formation in synaptosomes from the newborn, whereas in those from the adult, PGE2 and 11-deoxy PGE1 increased and M&B 28,767 decreased cAMP production. PGF2 alpha markedly increased IP3 synthesis in synaptosomes of the adult but not of the newborn.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1992

Biogenesis of myeloid bodies in regenerating newt (Notophthalmus viridescens) retinal pigment epithelium.

Myeloid bodies are believed to be differentiated areas of smooth endoplasmic reticulum membranes, and they are found within the retinal pigment epithelium in a number of lower vertebrates. Previous studies demonstrated a correlation between phagocytosis of outer segment disc membranes and myeloid body numbers in the retinal pigment epithelium of the newt. To test the hypothesis that myeloid bodies are directly involved in outer segment lipid metabolism and to further characterize the origin and functional significance of these organelles, we examined the effects on myeloid bodies of eliminating the source of outer segment membrane lipids (neural retina removal) and of the subsequent return of outer segments (retinal regeneration) in the newt Notophthalmus viridescens. Light- and electron-microscopic analysis demonstrated that myeloid bodies disappeared from the pigment epithelium within six days of neural retina removal. By week 6 of regeneration, rudimentary photoreceptor outer segments were present but myeloid bodies were still absent. However, at this time, the smooth endoplasmic reticulum in some areas of the retinal pigment epithelial cells had become flattened, giving rise to small (0.5 micron long), two-to-four layer-thick lamellar units, which are myeloid body precursors. Small myeloid bodies were first observed one week later at week 7 of retinal regeneration. This study revealed that newt myeloid bodies are specialized areas of smooth endoplasmic reticulum. It also showed that a contact between functional photoreceptors and the retinal pigment epithelium is essential to the presence of myeloid bodies in the epithelial cells.

Animals↗

PubMed1992

Phospholipid composition of myeloid bodies from chick retinal pigment epithelium.

The phospholipid composition of a myeloid body (MB) enriched subcellular fraction of chick retinal pigment epithelium (RPE) was determined in order to further characterize the origin and functional significance of these lamellar membrane organelles. The major MB phospholipids found were phosphatidylcholine and phosphatidylethanolamine which represented 43% and 34% of the total MB lipids respectively. Sphingomyelin and phosphatidylinositol comprised the remaining detectable phospholipids. The fatty acyl chain composition of all detected phospholipids showed that the long-chain polyunsaturated fatty acids [arachidonic (20:4 n-6), docosapentaenoic (22:5 n-3) and docosahexaenoic (22:6 n-3)] account for greater than 45% of the fatty acids in MB membranes. This high proportion of long-chain polyunsaturated fatty acids in MBs is particularly striking when compared to the long-chain fatty acid composition of the photoreceptor outer segments from this predominantly cone retina which contains less than 25% long-chain polyunsaturated fatty acids. The results from this study clearly demonstrate that MB lipids represent a significantly enriched pool of long-chain polyunsaturated fatty acids.

Animals↗

PubMed1986

Wavelength modulation by molecular environment in visual pigments.

The absorption and regenerability characteristics are compared for rhodopsin contained in rod outer segment membranes and purified in a series of alkyl sucrose esters. It is found that membrane-bound rhodopsin has maximum absorbance from 504 to 500 nm between 1.5 and 40 degrees C. After purification, rhodopsin absorbance can be blue-shifted by up to 6 nm, depending on the detergent species used. Only the longest chain sucrose esters give purified rhodopsin with maximum absorbance comparable to that of the native pigment. In the same manner, detergent-purified rhodopsin will be easily regenerated as long as its native spectral characteristics are maintained. Sucrose esters thus prove to be mild enough to maintain rhodopsin functionality with respect to these two properties and could probably be used successfully to maintain other membrane proteins' integrity.

Animals↗

PubMedDate not supplied

Characterization and ontogeny of PGE2 and PGF2 alpha receptors on the retinal vasculature of the pig.

The vasoconstrictor effects of PGE2 and PGF2 alpha are less pronounced on retinal vessels of the newborn than of the adult pig. We tested the hypothesis that the decreased vasomotor response to these prostaglandins might be due to relatively fewer receptors and/or different receptor subtypes (in the case of PGE2) on retinal vessels of the newborn animal. Binding studies using [3H]PGE2 and [3H]PGF2 alpha revealed that PGE2 (EP) and PGF2 alpha (FP) receptor densities in retinal microvessel membrane preparations from newborn animals were approximately 25% of those found in vessels from the adult. The Kd for PGF2 alpha did not differ; however, the Kd for PGE2 was less in newborn than in adult vessels. Competition binding studies using AH 6809 (EP1 antagonist), butaprost (EP2 agonist), M/+B 28,767 (EP3 agonist), and AH 23848B (EP4 antagonist) suggested that the retinal vessels of the newborn contained approximately equal number of EP1 and EP2 receptor subtypes whereas the main receptor subtype in the adult vessels was EP1. In addition, PGE2 and butaprost produced comparable increases in adenosine 3',5'-cyclic monophosphate synthesis in newborn and adult vessels. PGE2, 17-phenyl trinor PGE2 (EP1 agonist) and PGF2 alpha caused a 2.5 to 3-fold greater increase in inositol 1,4,5-triphosphate (IP3) formation in adult than in newborn preparations. It is concluded that fewer PGF2 alpha receptors and an associated decrease in receptor-coupled IP3 formation in the retinal vessels of the newborn could lead to weaker vasoconstrictor effects of PGF2 alpha on retinal vessels of the newborn than of adult pigs; fewer EP1 receptors (associated with vasoconstriction) and a relatively greater proportion of EP2 receptors (associated with vasodilation) might be responsible for the reduced retinal vasoconstrictor effects of PGE2 in the newborn.

Age Factors↗