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Biomedical subjects

B A Weissman

Publications and source records attributed to B A Weissman.

At least 37 records · Page 2Linked to original sources
PubMed1992

NG-nitro-L-arginine enhances neuronal death following transient forebrain ischemia in gerbils.

Experiments were performed with Mongolian gerbils to study the effect of the specific nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) on ischemic brain damage induced by 5 min bilateral carotid occlusion. A single i.p. injection of L-NNA did not result in any neuronal loss in the central nervous system. In animals undergoing ischemia, a selective destruction of hippocampal CA1 cells was observed whereas pretreatment with 50 mg/kg L-NNA 4 h before administration of ischemia produced significantly more extensive cell damage in the hippocampus and other brain regions. These findings demonstrate that in this model inhibition of nitric oxide generation augments ischemia-induced neuronal cell injury in the brain.

Animals↗
PubMed1992

The "L" in Dk/L.

We measured the Dk (oxygen permeability) of one specific hydrogel contact lens material (phemfilcon A, nominally 38% water content and ionic) by use of the conventional single chamber polarographic technique at 35 degrees C. When corrected for the boundary and edge effect, Dk was found to be 13 x 10(-11) cm2 ml O2/s ml mm Hg. (These units will be used for this term throughout the remainder of this report.) We also used the polarographic cathode as a model cornea to measure the Dk/L (oxygen transmissibility) of 7 powered contact lenses (-5 to +15 D) made from the same material by the same manufacturer. We found values ranging from 5 to 15 x 10(-9) cm ml O2/s ml mm Hg. (These units will also be used for this term throughout this report.) From analysis of these data, we found that any reasonable model (of the several previously proposed) for L could be used to predict the polarographically measured oxygen transmissibility of the low minus (-5 to -1 D) powered contact lenses, but that plus powered lenses, at least on this measurement apparatus, give Dk/L values that are closer to predictions based on the observed Dk and central thickness rather than any version of average thickness.

Contact Lenses↗
PubMed1992

Influence of polarographic cathode diameter on measured oxygen transmissibility of hydrogel contact lenses with optical power.

The oxygen transmissibility of a contact lens is defined as its oxygen permeability (Dk) divided by its thickness (L). Transmissibility can be obtained from separate measurements of Dk and L, or from a single measurement of oxygen flux through the lens (as for example by the polarographic method). Dk/L of hydrogel contact lenses with optical power measured by the polarographic method was compared with Dk/L calculated from separate measurements of Dk and L. Polarographic sensors of different cathode diameters were used to show the effect of the area over which the flux is measured on the observed Dk/L. Dk/L from oxygen flux measured by the polarographic sensor was found to be a function of the optical power of the lens and cathode diameter. Dk/L calculated from separately determined Dk and L for optically powered lenses was found to be a function of Dk and the choice of L (central or average).

Contact Lenses↗
PubMed1992

Antagonism studies with BMY-7378 and NAN-190: effects on 8-hydroxy-2-(di-n-propylamino)tetralin-induced increases in punished responding of pigeons.

The purported serotonin (5-HT)1A antagonists BMY-7378 and NAN-190 were examined in pigeons for their potential to block the effects of the prototypical 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on punished ("conflict") and unpunished behavior and for their binding affinity at the 5-HT1A receptor site labeled by [3H]-8-OH-DPAT. Although BMY-7378 and NAN-190 both displayed high affinity for the 5-HT1A receptor (IC50 values of 0.8 and 7.5 nM, respectively), their effects, when administered alone, as well as in combination with 8-OH-DPAT, were distinct. 8-OH-DPAT (0.3-3.0 mg/kg) produced large increases in punished responding at doses that did not affect or that decreased unpunished responding. Administration of NAN-190 (1.0-3.0 mg/kg) did not increase punished responding, whereas BMY-7378 (1.0-5.6 mg/kg) slightly increased behavior suppressed by punishment. Pretreatment with BMY-7378 attenuated the rate-increasing effects of 8-OH-DPAT on punished responding; however, these effects were accompanied by dose-dependent enhancement of the rate-decreasing effects of 8-OH-DPAT on unpunished responding. In contrast, NAN-190 blocked the rate-increasing effects of 8-OH-DPAT on punished responding and also reversed the rate-decreasing effects of 8-OH-DPAT on responding that was not punished. Pretreatment with NAN-190 failed to block increases in punished responding produced by 0.1 to 1.0 mg/kg of the benzodiazepine midazolam. These data suggest that NAN-190 may be characterized as an antagonist and BMY-7378 a partial agonist with respect to 5-HT1A-induced behavioral changes observed in the conflict procedure with pigeons.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Polarographic oxygen permeability measurement of silicone elastomer contact lens material.

The flexible silicone elastomer is a contact lens material of substantial potential, primarily because of its high theoretical oxygen permeability (Dk). Review of the previous literature indicates some difficulty in precisely determining the Dk of the silicone elastomer, and quantification of this permeability value ranges from 50 to 340 x 10(-11) cm2 ml 02/sec ml mmHg by various techniques. (The exponential term 10(-11) and the units of Dk will be omitted hereafter in this text). We herein report use of the single-chamber polarographic technique, with edge and boundary corrections, to arrive at a value of 190 with a standard deviation (SD) of 79 for the Dk of one silicone elastomer contact lens material. The excessive SD suggests that an improved method to evaluate contact lens materials with Dk values in excess of 30-50 should be determined.

Contact Lenses↗
PubMed1991

Clinical application of the oxygen transmissibility of powered contact lenses.

Stipulation of the oxygen transmissibility (Dk/L) of a contact lens based upon oxygen permeability (Dk) and nominal lens thickness (L) can be misleading since center thickness, average thickness, and hence Dk/L of a contact lens vary with lens power. While earlier confusion regarding determination of Dk has now been resolved, this data has yet to be fully incorporated into a clinically applicable model. We developed a graphical solution describing variations in Dk/L with power for a representative sample of currently available hydrogel and rigid contact lenses. The Dk/L is found to be optimal for lenses of low minus power (approximately -2.50 D). The model presented here will assist practitioners in assessing the potential oxygen performance of different lens designs with respect to a given power. We advocate that lens manufacturers print the average Dk/L on lens packaging, according to the model described in this paper, along with the parameters that are usually stated.

Contact Lenses, Hydrophilic↗
PubMed1991

Oxygen transmissibility of disposable hydrogel contact lenses.

We measured the central and mid-peripheral thicknesses of three "disposable" hydrogel contact lens designs of varying powers. These measurements allowed calculation of the areal average lens thicknesses (over a central 6 mm chord), which in turn allowed calculation of predicted oxygen transmissibility (Dk/L) for the lenses studied (using previously reported values for measured oxygen permeability [Dk] of these materials). Dk/L values for the disposable hydrogel lenses tested were found to range from 9 to 17 x 10(-9) cm mL O2/sec mL mmHg.

Contact Lenses, Hydrophilic↗
PubMed1990

Presence of peripheral benzodiazepine binding sites on primary rat skeletal fibroblasts.

Employing [3H]Ro5-4864 as a radioligand, the existence of peripheral benzodiazepine binding sites in rat hind limb skeletal fibroblasts was explored. Saturable, high affinity binding of this ligand is described for fibroblasts and cell membrane preparations, demonstrating a pharmacological profile characteristic for such receptors. The binding of [3H]Ro5-4864 exhibited higher affinity and density in fibroblasts compared to membrane preparations. A quaternaryamine derivative of PK 11195 showed a similar potency as a displacer of [3H]Ro5-4864 in both preparations. The data suggest that peripheral benzodiazepine receptors are present in the plasma membrane of primary mammalian fibroblasts.

Animals↗
PubMed1990

Aprophit: an irreversible antagonist for muscarinic receptors.

The development of selective irreversible ligands has proven to be an invaluable technique for the isolation, purification and characterization of many receptor proteins. An isothiocyanato-derivative of the muscarinic antagonist aprophen was synthesized and evaluated as a potential irreversible ligand for muscarinic receptors. This compound (aprophit) displaced [3H]N-methylscopolamine binding from rat cerebral cortex with a Ki of 3.1 x 10(-7) M. The inhibition was concentration-dependent and could not be reversed by extensive washing. Aprophit inhibited the acetylcholine-stimulated release of catecholamines from isolated, perfused guinea pig adrenal glands in a concentration-dependent manner. This inhibition was not reversed by perfusing the tissue with Locke's solution and was not due to a non-selective acylation by the isothiocyanate function. The data suggest that aprophit is selectively acylating muscarinic receptor proteins and thus may be useful in their further characterization.

Adrenal Glands↗
PubMed1990

Oxygen permeability of disposable soft contact lenses.

Disposable contact lenses are inexpensive hydrogel lenses that are approved for both daily and extended wear. Confusion may exist regarding the physical properties of disposable contact lenses. We used the single-chamber polarographic oxygen permeability measurement method, corrected for both boundary and edge effects, to determine objectively the oxygen permeability of three brands of disposable contact lenses. The oxygen permeability values determined for each lens material are as follows: Acuvue, 18 x 10(-11) cm2 ml O2/sec ml mm Hg (Dk); NewVues, 15 x 10(-11) Dk; and SeeQuence, 9 x 10(-11) Dk. This demonstrates that the inexpensive production techniques, which confer a relatively low unit expense, do not change the physical properties of the hydrogel materials as they relate to oxygen permeability and transmissibility. We concluded that hypoxic stress to the cornea is just as likely when using a disposable contact lens as it is when using a conventional reusable soft hydrogel lens of similar composition and water content.

Contact Lenses, Hydrophilic↗
PubMed1990

A novel action of glucocorticosteroid in inhibition of leukotriene C4 production by rat basophilic leukemia cells: suppression of the elevation of cytosolic free Ca2+ induced by antigen.

Rat basophilic leukemia (RBL-2H3) cells serve as a model to examine the role of elevated internal Ca2+ concentration ([Ca2+]i), following antigen (DNP10BSA)-induced stimulation of leukotriene C4 (LTC4) formation. A novel action of hydrocortisone (HC), to reduce increased [Ca2+]i and consequently inhibit LTC4 formation is assessed. Half-maximal time for elevation of [Ca2+]i induced by antigen was less than 1 min, and maximal elevation of [Ca2+]i (3-fold increase) was reached within 2-3 min. This high [Ca2+]i level waned gradually by 27% during 20 min of incubation. For induction of LTC4 formation, however, there was a refractory period of about 2 min, and half-maximal elevation was at 11 min. Following pretreatment with HC, the antigen-stimulated increase in [Ca2+]i was stunted by 41% at 2-3 min and by 73% at 20 min. LTC4 formation was almost abolished. There was a lag period of at least 2 h to observe any inhibition in both parameters, and the maximal inhibition was about 4 h. Cycloheximide, and receptor antagonist to glucocorticosteroid (RU486) completely prevented the inhibitory effects of HC on elevated [Ca2+]i and LTC4 formation. Estradiol and aldosterone (each at 2.10(-6) M) were virtually inactive, while another glucocorticosteroid, dexamethasone (2.10(-7) M) markedly suppressed antigen induction in both parameters. It is proposed that the inhibitory effect of HC on the formation of LTC4 could be attributed mainly to its ability to reduce elevated [Ca2+]i.

Animals↗
PubMed1990

Interactions between nitrogen oxide-containing compounds and peripheral benzodiazepine receptors.

Nitrogen oxide-containing compounds displaced the peripheral benzodiazepine ligand [3H]Ro5-4864 from guinea pig membrane preparations. Sodium nitroprusside (SNP) was the most potent (IC50 = 5.61 +/- 1.72 x 10(-5) M). Moreover, its ability to bind to these receptors showed marked tissue variability (heart greater than kidney much greater than cerebral cortex). When tested on rat atrium, SNP by itself had no effect on basal inotropy or the increase in inotropy induced by (-)-S-BAY K 8644. In contrast, Ro5-4864 potentiated the marked increase in inotropy induced by (-)-S-Bay K 8644, and SNP completely abolished the potentiation of inotropy observed with Ro5-4864. Since peripheral benzodiazepine receptors are associated with calcium mobilization in the heart, these findings may indicate that some of the clinical effects of nitric oxide-generating drugs could be mediated by these receptors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Age-related changes in the cholinergic components within the central nervous system. II. Working memory impairment and its relation to hippocampal muscarinic receptors.

Cognitive performance in aging Wistar rats was monitored using the radial arm maze and the latter was correlated with the density of muscarinic receptors in the CNS, using quantitative in vitro receptor autoradiography. Significant working memory deficits were observed in 12, 17 and 24-month-old rats as compared to 3-month-old animals. In addition, the number of the muscarinic receptors declined significantly with age (from 27 to 42% depending on the brain region sampled) utilising [3H]QNB and [3H]PZ receptor binding assays. The above trend became evident already at the age of 12 months. The present findings support the association of central cholinergic activity with memory processes.

Age Factors↗
PubMed1990

Is daily wear better than extended wear? Arguments in favor of daily wear.

The use of contact lenses for extended wear appears to be accompanied by an increase in several complications, the most serious of which is corneal infection. It has been proposed that infection is due to corneal epithelial layer microtrauma and lens care system contamination, but noncompliance, contamination of care systems, and microtrauma [especially among keratoconics and polymethylmethacrylate (PMMA) lens users, for example] are so common in daily wear that we believe they are insufficient to explain the approximately sixfold increase in the rate of corneal infection with extended wear. Perhaps the chronic hypoxic stress of extended wear use of contact lenses substantially reduces the resistance of the epithelium to either injury or microbial infection. Until evidence is provided that new contact lenses have sufficient oxygen transmissibility (Dk/L) to fully satisfy corneal oxygen needs under extended wear conditions, and the extended wear use of such lenses is thoroughly tested in a study population, we believe that the majority of contact lens patients should be maintained on daily wear schedules.

Contact Lenses, Extended-Wear↗
PubMed1990

Interactions between peripheral-type benzodiazepine receptor ligands and an activator of voltage-operated calcium channels.

The effects of the peripheral-type benzodiapine receptor (PBR) ligands Ro 5-4864 and PK 11195 were studied in the spontaneously beating guinea pig atrium and in a model for myocardial ischemia in the rat. In the former, Bay K 8644 produced positive chronotropic and inotropic responses; intracarotid administration of this agonist (5 or 10 micrograms kg-1) to anesthetized rats elicited a transient increase in mean arterial blood pressure accompanied by alterations in the ECG pattern. Ro 5-4864 and PK 11195 (10 microM) completely blocked the positive chronotropic effect of Bay K 8644 in the atrium, PK 11209, a structural analog of PK 11195 with a low affinity for PBR, was inactive, and the central benzodiazepine receptor ligand clonazepam had a marginal effect. Ro 5-4864 potentiated whereas PK 11195 inhibited the myocardial ischemia produced by Bay K 8644 in the rat. Furthermore, PK 11195 blocked the combined response to Bay K 8644 and Ro 5-4864. Addition of Ro 5-4864 (10 microM) to the organ bath potentiated the inotropic effect of Bay K 8644 in the atria; PK 11195 at the same concentration inhibited this effect. Clonazepam and PK 11209 were both inactive in this regard. Nifedipine, a potent calcium channel antagonist, completely blocked the inotropic and chronotropic responses to Bay K 8644. PK 11195 and Ro 5-4864 did not affect this action. These findings strongly suggest that there is a functional association between PBR and voltage-operated calcium channels in the guinea pig atrium and rat cardiovascular system.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Giant papillary conjunctivitis associated with elevated corneal deposits.

A patient presented with central corneal scarring and neovascularization associated with elevated deposits that were shown to be keratin and calcium. Giant papillary conjunctivitis (GPC) was noted at a corresponding location in the palpebral conjunctiva. The lid reaction resolved after the elevated corneal deposits were debrided. A rigid gas-permeable contact lens was then fitted for visual rehabilitation. Either foreign bodies or elevated corneal deposits may cause GPC.

Adult↗
PubMed1990

Oxygen permeability of collagen shields.

The oxygen permeability (Dk) of ten 24-hr collagen shields was measured directly by polarographic methodology at approximately 2 hr of hydration. Edge and boundary effects were included in the calculations. Dk was found to be approximately 26 x 10(-11) cm ml O2/sec ml mmHg at 35 degrees C. Mean water content of the shields was 65.7% (SD = 1.0%) as measured by a hand refractometer. Therefore, the projected oxygen transmissibility of collagen shields is expected to be compatible with normal corneal metabolism.

Bandages↗