Novel and selective 5-HT2C/2B receptor antagonists as potential anxiolytic agents: synthesis, quantitative structure-activity relationships, and molecular modeling of substituted 1-(3-pyridylcarbamoyl)indolines

The synthesis, biological activity, and molecular modeling of a novel series of substituted 1-(3-pyridylcarbamoyl)indolines are reported. These compounds are isosteres of the previously published indole urea 1 (SB-206553) and illustrate the use of aromatic disubstitution as a replacement for fused five-membered rings in the context of 5-HT2C/2B receptor antagonists. By targeting a region of space previously identified as sterically allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor, we have identified a number of compounds which are the most potent and selective 5-HT2C/2B receptor antagonists yet reported. 46 (SB-221284) was selected on the basis of its overall biological profile for further evaluation as a novel, potential nonsedating anxiolytic agent. A CoMFA analysis of these compounds produced a model with good predictive value and in addition good qualitative agreement with both our 5-HT2C receptor model and our proposed binding mode for this class of ligands within that model.     

Optimum mixtures of stabilizers for polypropylene monofilaments and films

Conclusions The joint use of antioxidants of the phenolic type and SHA causes manifestation of an antagonistic action. By choosing optimum dosages of the stabilizers, this adverse effect can be reduced to a minimum.The fundamental possibility of replacing the imported stabilizers Tinuvin 327, Cyasorb UV-531, and Irganox 1010 by the domestic products diacetam 5, benzon OA, fenozan 23, and fenozan 28 in the production of PP and fibrous materials based on it has been demonstrated.In a complex of properties, the most effective mixed composition in articles based on PP is the one which contains diacetam 5 (0.2% by wt.) fenozan 23 (0.1% wt.), phosphite NF (0.2% by wt.), and DSTDP (0.2% by wt.).Translated from Khimicheskie Volokna, No. 5, pp. 10–12, September–October, 1984.     

Direct immunocytochemical evidence for the transfer of glutamine from glial cells to neurons: use of specific antibodies directed against the d-stereoisomers of glutamate and glutamine

We have raised antibodies against D-stereoisomers of the amino acids glutamate and glutamine. These stereoisomers are not naturally occurring in mammals but can be taken up into cells by transporters that normally handle the endogenous L-amino acids. Exposure of isolated rabbit retinae to 50 microM D-glutamate resulted in a strong accumulation of D-glutamate, and hence immunoreactivity for D-glutamate in radial glial cells (Müller cells). By contrast the glutamatergic ganglion cells exhibited no immunoreactivity for D-glutamate. D-Glutamate can be converted into D-glutamine by the glial enzyme glutamine synthetase. Immunolabelling for D-glutamine revealed the presence of D-glutamine in somata of subsets of neurons including the glutamatergic ganglion cells. Labelling was also present in the inner plexiform layer, possibly indicating labelling of neuronal processes. These data indicate that after D-glutamate has been taken up into glial cells it is converted into D-glutamine. This D-glutamine is then exported from the glial cells and taken up by a subset of neurons, including the glutamatergic ganglion cells.     

Immunocytochemical evidence for an axonal localization of GABA in the optic nerves of rabbits, rats, and cats

We have examined, by light-microscopic immunocytochemistry, the distribution of GABA in the optic nerves of adult rabbits, rats, and cats. Within the optic nerves, immunoreactivity for GABA was restricted to a small subset of axons; some axons were strongly labelled, others weakly labelled, whilst most axons were unlabelled. Glia and other non-neuronal elements were always unlabelled. Our ability to detect GABA in optic nerve axons of adult mammals contrasts with previous reports that indicate a lack of GABA immunoreactivity in such axons. We suggest that this discrepancy may be due to the sensitivity of our immunocytochemical techniques which enable us to detect low concentrations of GABA.     

Effect of detonation coatings on the fatigue strength of components

Conclusions Examination of the fatigue resistance to the detonation layer showed that in the majority of the materials examined the endurance limit is similar to that of the nonsprayed component, whereas nickel was characterized by a large reduction of this parameter. The main characteristic of the performance of the hardened components which operate under cyclic loading is the fatigue resistance and not the strength of bonding with the substrate.The relationship between these parameters is ambiguous.The authors believe that the operation of the sprayed layer can be efficient in two extreme cases: The first case in which the layer is dense, with a minimum number of discontinuities, has satisfactory adhesion over the entire surface with the substrate and this material has sufficient fatigue resistance, and the second case in which the layer is of the conventional type has poor bonding with the substrate and does not operate under cyclic loading, i.e., does not interfere with operation of the component.It is evident that the contradicting data obtained in different investigations of the endurance limit are associated with the intermediate variant of the sprayed layer which is used on an increasing scale.Translated from Poroshkovaya Metallurgiya, No. 5(329), pp. 37–41, May, 1990.     

Protonation of Vion Anion-Exchange Chemisorbents

Protonation of weakly basic pyridinium and aliphatic amino groups in VION AN-1, AS-1, and AN-5 fibres was investigated during sorption of hexavalent chromium anions from aqueous solutions. It is shown that VION protonated fibre chemisorbents effectively capture the hexavalent chromium anion in the region of pH 1-3. It was found that in sorption of hexavalent chromium anions by strongly basic and protonated weakly basic chemisorbents, reactions related to reduction of hexavalent chromium to the penta- and trivalent states take place. A hypothesis is advanced concerning the effect of the basicity of the chemically active groups in the chemisorbents on complexation of hexavalent chromium anions.     

The Alabama Eye Bank: 25 years of giving sight

Modern Eye Banking had its start in the mid-1940's. However, it was not until the 1960's that eye banking grew to become a movement or even a necessary part of the health care delivery system in the state of Alabama. The Alabama Eye Bank has grown rapidly to become one of the largest corneal processing networks in the United States. Corneal transplant surgery remains highly successful in restoring sight. The contraindications for donor tissue should be clarified to all physicians and other health care professionals. The public should be make aware of the vision care available to them in the state of Alabama. The general public should be aware of how to become a pre-pledged eye donor, of research, teaching and transplantable tissue and also how they can be assured that their wishes are carried out at the time of their demise. Even with scheduled transplant surgery for all Alabamians, the need for the general public and medical professionals to be oriented and educated towards multi-organ and tissue donations is important.