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Biomedical subjects

Z Friedman

Publications and source records attributed to Z Friedman.

At least 55 records · Page 3Linked to original sources
PubMed1988

Human retinal pigment epithelial cells possess muscarinic receptors coupled to calcium mobilization.

Human retinal pigment epithelial (RPE) cells in culture demonstrated saturable specific binding of [3H]quinuclidinyl benzilate (QNB). Specific binding represents about 75% of total binding. Scatchard analysis yields a Kd of 0.178 nM and Bmax of 42 fmol/mg protein. Atropine and carbachol show typical displacement curves, and a Hill plot has a slope of 0.96, suggesting a homogeneous population of receptors. Muscarinic agonists have no effect on intracellular cyclic adenosine monophosphate levels in RPE cells measured by radioimmunoassay, nor do they alter the isoproterenol-induced stimulation of adenylate cyclase. However, both acetylcholine and carbachol cause a rapid increase in intracellular calcium concentration measured by the fluorescent indicator quin 2. Atropine reverses the calcium rise when added after agonist and prevents the rise when added prior to agonist. These data suggest that human RPE cells possess muscarinic receptors coupled to calcium mobilization.

Atropine↗
PubMed1987

Cyclic 3',5'-adenosine monophosphate modulates vascular endothelial cell migration in vitro.

Using a modified Boyden chamber assay, we have examined the effect of cyclic nucleotides on bovine aortic endothelial cell migration in vitro. Dibutyrl cyclic 3',5'-adenosine monophosphate (5 mM) inhibited endothelial cell random migration by 67% and inhibited fibronectin-induced chemotaxis by 75%. Agents which significantly stimulated adenylate cyclase activity in endothelial cell membranes were also effective inhibitors of endothelial cell migration. Timolol blocked both the isoproterenol-induced stimulation of adenylate cyclase and the ability of isoproterenol to inhibit endothelial cell migration. Caffeine and isoproterenol together had a greater inhibitory effect on endothelial cell motility than either alone. These data suggest that cAMP may modulate vascular endothelial cell migration in an inhibitory fashion.

Adenylyl Cyclases↗
PubMed1987

Characterization of adenylate cyclase in human retinal pigment epithelial cells in vitro.

Human retinal pigment epithelial cells in culture demonstrate adenylate cyclase activity. It is membrane-bound and modulated by GTP regulatory proteins. It is effectively activated only by beta-adrenergic agonists (L-isoproterenol greater than or equal to L-epinephrine greater than L-norepinephrine) and some prostaglandins (PGE1 and PGE2, but not PGF1 alpha). The adrenergic response appears to be mediated by beta-2 receptors. No inhibitory ligands could be demonstrated. Its characteristics, which are similar to functional adenylate cyclase complexes in other mammalian cells, and its selective and sensitive agonist responsiveness, suggest a possible physiologic role in the regulation of human retinal pigment epithelial-cell function.

Adenylyl Cyclases↗
PubMed1986

Cyclic 3',5'-adenosine monophosphate modulates retinal pigment epithelial cell migration in vitro.

Retinal pigment epithelial (RPE) cell migration has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR). Using a modified Boyden chamber assay, we have examined the effect of cyclic nucleotides on human RPE cell migration in vitro. Dibutyryl cyclic 3',5'-adenosine monophosphate (cAMP) (10(-3) mmol/L) inhibits RPE cell random migration by 83%, fibronectin-induced chemotaxis by 61%, and platelet-derived growth factor-induced chemotaxis by 68%. Random and directed migration of RPE cells is not significantly affected by 8-bromo cyclic 3',5'-guanosine monophosphate. Agents that significantly increase intracellular levels of cAMP are also inhibitors of RPE cell migration. Though there is a fairly good correlation for most drugs for their ability to stimulate cAMP production and their ability to inhibit cell migration, it is not perfect, suggesting that some drugs may modulate migration by more than one mechanism. Timolol blocked both the isoproterenol-induced stimulation of RPE adenylate cyclase and attenuated the ability of isoproterenol to inhibit RPE migration. These data suggest that cAMP may modulate RPE cell migration in an inhibitory fashion. Elucidation of the biochemical events involved in RPE cell migration could provide information that might be useful in planning a strategy to attempt pharmacologic control of proliferative vitreoretinopathy.

Adenylyl Cyclases↗
PubMed1986

Essential fatty acid consideration at birth in the premature neonate and the specific requirement for preformed prostaglandin precursors in the infant.

The essentiality of certain PUFA is probably related to their capability to be incorporated into lipids and to act as precursor in the formation of ecosanoids. Esterified to phospholipids, the EFA influence the physico-chemical characteristics of biomembranes. Normal growth of infants is dependent upon an adequate supply of EFA. The human fetus, like the adult, is unable to synthesize the EFA, which must therefore be derived from the maternal circulation and pass through the placenta. Increased concentration of the polyenoic fatty acids with advanced gestational age may result from increased synthetic activity of these fatty acids by the fetus or the placenta or by preferential transfer of these fatty acids across the placenta. Several clinical manifestations have been ascribed in the human infant to prolonged EFA deficiency; however, none of these findings were noted in a group of sick newborn infants with very rapid onset of deficiency. Platelet dysfunction, decreased prostaglandin biosynthesis and turnover and altered pulmonary surfactant are among the effects of EFA deficiency on infants. Supplementation of the diet with EFA, parenterally or by the inunction of oil rich in linoleic acid, were reported to alleviate the symptoms of EPA deficiency. The minimal estimated requirement of linoleic acid is 1% of calories and 4% is an optimal intake. Most diets, including human breast milk, infant formulas and parenteral fat emulsions, far exceed the optimal intake of linoleic acid. Relatively little is known about the possible effects of high levels of linoleate in the diet.

Blood Platelets↗
PubMed1986

Prostaglandins in breast milk.

Levels of prostaglandin E2, prostaglandins F2 alpha and prostacyclin (measured as 6-keto PGF1 alpha) were measured by radioimmunoassay in aliquots of foremilk and hindmilk obtained at different stages of lactation, (colostrum, transitional and mature milk), from ten healthy nursing mothers who delivered at term. Immunoreactive prostaglandins E2, F2 alpha and the stable metabolite of prostacyclin 6-keto PGF1 alpha were detected in all fresh human milk samples but not in cow's milk-based formulas. The source of prostaglandins and prostacyclin in breast milk is related to local synthesis of the mammary gland and to the synthesis by the cellular elements of breast milk but not to their level in the maternal circulation.

Animals↗
PubMed1985

Topical acetazolamide and methazolamide delivered by contact lenses.

Topical acetazolamide has been previously found to be ineffective in lowering intraocular pressure (IOP). Using high-water-content soft contact lenses (Sauflon PW) soaked in acetazolamide, we observed a statistically significant ipsilateral decrease in IOP of 6.3 +/- 0.4 mm Hg in the treated eyes of albino rabbits. The duration of the effect was up to 7 1/2 hours. Methazolamide-soaked contact lenses produced a maximum unilateral reduction of similar magnitude but shorter duration. Both serum and aqueous humor analyses for pH, carbon dioxide pressure, bicarbonate, and base excess indicate that acetazolamide delivered by soft contact lenses is able to penetrate the cornea in sufficient concentration to lower IOP by a local mechanism in rabbits without significant systemic absorption.

Acetazolamide↗
PubMed1984

Prostaglandin formation in the isolated human ductus arteriosus, aorta, pulmonary and umbilical arteries.

The prostaglandins comprise a large family of substances that includes primary prostaglandins, prostacyclin and thromboxane, all of which exhibit some vascular activity. The activity of each prostaglandin may be species - and organ - dependent, and the type of prostaglandin produced in a tissue is often dependent on the presence of terminal enzyme systems in that tissue. The prostaglandin endoperoxide PGH2 serves as a common intermediate for the enzymatic production of prostaglandins, thromboxanes and prostacyclin. We have obtained information on the biosynthesis of these compounds by the human ductus arteriosus, aorta, pulmonary and umbilical arteries in vitro. Vascular tissue samples were obtained from two fetuses of 16 to 18 weeks of gestation, two newborns of 26 and 35 weeks of gestation and in nine term infants. The vascular tissue samples were incubated with [1-14C]-arachidonic acid and/or [1-14C]-prostaglandin endoperoxide (PGH2). The study demonstrates the formation of prostaglandins and prostacyclins from all the vascular tissues and the formation of thromboxanes from the umbilical artery. The study implies that the above vessels contain "prostaglandin synthetase" enzymes as early as 16 weeks of gestation.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Giant papillary conjunctivitis following cataract extraction.

Out of a series of 600 cataract extractions, 14 patients were found to have giant papillary conjunctivitis (GPC) due to 10-0 nylon sutures. When renewed conjunctival irritation appears weeks or months after surgery, GPC should be suspected and confirmed by eversion of the upper eyelid at the slit lamp. Free edges of protruding corneoscleral nylon sutures should be looked for. Signs and symptoms of GPC disappear within one to four weeks after removal of the offending suture.

Aged↗
PubMed1982

Myofibrillar protein degradation in premature infants with respiratory distress as assessed by 3-methylhistidine and creatinine excretions.

The skeletal muscle content of 3-methylhistidine has been measured in two fetuses and four infants of 15 to 38 wk of gestation. The average concentration of skeletal muscle 3-methylhistidine is 1.11, 2.64, and 3.28 (mumol/mixed protein) for fetuses of 15 to 18 of gestation and infants of 26 to 32 and 37 to 38 wk of gestation, respectively. Myofibrillar protein degradation has been measured by the rate of 3-methylhistidine excretion in premature infants suffering from respiratory distress and weighing between 1310 and 2420 g. In 26 balance studies in six infants, total muscle protein breakdown varied from 0.92 to 1.58 g day-1 kg-1 body weight. Calculated fractional catabolism of myofibrillar protein varied from 0.38 to 1.07% per day. A trend toward a higher rate of myofibrillar protein degradation is noted during the infants' acute illness and during their rapid growing phase.

Creatinine↗
PubMed1982

Synthesis of new haloperidol analogues and characterization of their interactions with alpha-adrenoceptors in rat parotid slices and human platelet membranes.

1 The synthesis of several butyrophenone analogues of haloperidol is described. 2 The effects of these compounds on alpha-adrenoceptors were evaluated by examining their ability to reduce alpha 1-stimulated K+ release from rat parotid slices and to displace [3H]-phentolamine from human platelet membrane alpha 2-adrenoceptors. 3 The affinity of haloperidol and its analogues for alpha 1-receptors was found to be 1 to 2 orders of magnitude greater than that for alpha 2-adrenoceptors. These observations suggest that most of the alpha-adrenoceptor activity of butyrophenones results from their interaction with alpha 1-adrenoceptors. 4 The relatively high affinity of the butyrophenones for alpha 1-adrenoceptors suggests that they may be useful as probes in studies of alpha 1-adrenoceptors in these and other tissues.

Animals↗
PubMed1982

Ocular and systemic effects of acetazolamide in nephrectomized rabbits.

The effects of acetazolamide on intraocular pressure (IOP) were studied on rabbits previously nephrectomized to eliminate the renal effects of the drug. Administration of acetazolamide (5 mg/kg i.v.) reduced IOP from a baseline of 15.2 to 12.2 mm Hg 2 hr later. This dose was found not to alter arterial blood pH, pCO2, bicarbonate, or base excess. However, 4 hr after drug administration anterior chamber aqueous humor showed significant reductions in bicarbonate, pH, and base excess, whereas aqueous humor ascorbate was significantly elevated. Administration of acetazolamide 15 to 50 mg/kg i.v.) to nephrectomized rabbits caused significant acidosis and pCO2 retention, presumably related to red blood cell carbonic anhydrase inhibition. IOP reduction at these higher doses was greater than that which followed the 5 mg/kg administration.

Acetazolamide↗
PubMed1981

Retrolental fibroplasia: efficacy of vitamin E in a double-blind clinical study of preterm infants.

We performed a double-blind study in 101 preterm infants who weighed less than or equal to 1500 g at birth, who had respiratory distress, and who survived for at least four weeks, to evaluate the efficacy of oral vitamin E in preventing the development of retrolental fibroplasia. Weekly indirect ophthalmologic examinations begun when the infants were three weeks old revealed a significant decrease in the incidence of retrolental fibroplasia greater than or equal to Grade III (P less than 0.03) and greater than or equal to Grade II (P less than 0.05) (McCormick classification) in the 50 infants given 100 mg of vitamin E per kilogram of body weight per day as compared with 51 given 5 mg per kilogram per day (controls). When multivariate analysis was applied to the controls, five risk factors were identified: gestational age, level and duration of administration oxygen, intraventricular hemorrhage, sepsis, and birth weight. When multivariate analysis was applied to both control and treatment groups, the severity of retrolental fibroplasia was found to be significantly reduced in infants given 100 mg of vitamin E (P = 0.012).

Administration, Oral↗