BCLA CLEAR Presbyopia: Management with contact lenses and spectacles.

This paper seeks to outline the history, market situation, clinical management and product performance related to the correction of presbyopia with both contact lenses and spectacles. The history of the development of various optical forms of presbyopic correction are reviewed, and an overview is presented of the current market status of contact lenses and spectacles. Clinical considerations in the fitting and aftercare of presbyopic contact lens and spectacle lens wearers are presented, with general recommendations for best practice. Current options for contact lens correction of presbyopia include soft simultaneous, rigid translating and rigid simultaneous designs, in addition to monovision. Spectacle options include single vision lenses, bifocal lenses and a range of progressive addition lenses. The comparative performance of both contact lens and spectacle lens options is presented. With a significant proportion of the global population now being presbyopic, this overview is particularly timely and is designed to act as a guide for researchers, industry and eyecare practitioners alike.

1-Bromo-3-(1',1'-dimethylalkyl)-1-deoxy-Δ(8)-tetrahydrocannabinols: New selective ligands for the cannabinoid CB(2) receptor.

Δ(8)-Tetrahydrocannabinol (26), 3-(1',1'-dimethylbutyl)- (12), 3-(1',1'-dimethylpentyl)- (13), 3-(1',1'-dimethylhexyl)- (14) and 3-(1',1'-dimethylheptyl)-Δ(8)-tetrahydrocannabinol (15) have been converted into the corresponding 1-bromo-1-deoxy-Δ(8)-tetrahydrocannabinols (25, 8-11). This was accomplished using a protocol developed in our laboratory in which the trifluoromethanesulfonate of a phenol undergoes palladium mediated coupling with pinacolborane. Reaction of this dioxaborolane with aqueous-methanolic copper(II) bromide provides the aryl bromide. The affinities of these bromo cannabinoids for the cannabinoid CB(1) and CB(2) receptors were determined. All of these compounds showed selectivity for the CB(2) receptor and one of them, 1-bromo-1-deoxy-3-(1',1'-dimethylhexyl)-Δ(8)-tetrahydrocannabinol (10), exhibits 52-fold selectivity for this receptor with good (28nM) affinity.

Ciliary abnormalities due to defects in the retrograde transport protein DYNC2H1 in short-rib polydactyly syndrome.

The short-rib polydactyly (SRP) syndromes are a heterogeneous group of perinatal lethal skeletal disorders with polydactyly and multisystem organ abnormalities. Homozygosity by descent mapping in a consanguineous SRP family identified a genomic region that contained DYNC2H1, a cytoplasmic dynein involved in retrograde transport in the cilium. Affected individuals in the family were homozygous for an exon 12 missense mutation that predicted the amino acid substitution R587C. Compound heterozygosity for one missense and one null mutation was identified in two additional nonconsanguineous SRP families. Cultured chondrocytes from affected individuals showed morphologically abnormal, shortened cilia. In addition, the chondrocytes showed abnormal cytoskeletal microtubule architecture, implicating an altered microtubule network as part of the disease process. These findings establish SRP as a cilia disorder and demonstrate that DYNC2H1 is essential for skeletogenesis and growth.

Synthesis and pharmacology of 1-deoxy analogs of CP-47,497 and CP-55,940.

A series of 1-deoxy analogs of CP-47,497 (8 and 13, n=0-7) and 1-deoxy analogs of CP-55,940 (9, n=0-7) have been synthesized and their affinities for the cannabinoid CB(1) and CB(2) receptors have been determined. Although the majority of these compounds exhibit selectivity for the CB(2) receptor, none have greater than modest affinity for either receptor. The interactions of these 1-deoxy nontraditional cannabinoids with the CB(2) receptor are discussed.

Structure-activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB(1) and CB(2) receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB(2) receptor agonists.

In an effort to improve indole-based CB(2) cannabinoid receptor ligands and also to develop SAR for both the CB(1) and CB(2) receptors, 47 indole derivatives were prepared and their CB(1) and CB(2) receptor affinities were determined. The indole derivatives include 1-propyl- and 1-pentyl-3-(1-naphthoyl)indoles both with and without a 2-methyl substituent. Naphthoyl substituents include 4- and 7-alkyl groups as well as 2-, 4-, 6-, 7-methoxy and 4-ethoxy groups. The effects of these substituents on receptor affinities are discussed and structure-activity relationships are presented. In the course of this work three new highly selective CB(2) receptor agonists were identified, 1-propyl-3-(4-methyl-1-naphthoylindole (JWH-120), 1-propyl-2-methyl-3-(6-methoxy-1-naphthoylindole (JWH-151), and 1-pentyl-3-(2-methoxy-1-naphthoylindole (JWH-267). GTPgammaS assays indicated that JWH-151 is a full agonist at CB(2), while JWH-120 and JWH-267 are partial agonists. Molecular modeling and receptor docking studies were carried out on a set of 3-(4-propyl-1-naphthoyl)indoles, a set of 3-(6-methoxy-1-naphthoyl)indoles and the pair of N-pentyl-3-(2-methoxy-1-naphthoyl)indoles. Docking studies indicated that the CB(1) receptor affinities of these compounds were consistent with their aromatic stacking interactions in the aromatic microdomain of the CB(1) receptor.

La Comisión de Hospitales e Instituciones de APdeBA: una reflexión sobre su historia / APdeBAãs Committee for Hospitals and Institutions: A reflection about his history

Partiendo de las teorizaciones de autores psicoanalíticos acerca de la inserción de los sujetos en las Instituciones, se hace un relato de la historia de los nueve años de existencia de la Comisión de Hospitales e Instituciones en el seno de APdeBA. Se destaca la labor realizada en Docencia y Supervisión, y se citan trabajos científicos producidos por los miembros participantes. Se subraya la necesidad de los aportes interdisciplinarios entre Psicoanálisis y Medicina (AU)

La Comisión de Hospitales e Instituciones de APdeBA: una reflexión sobre su historia / APdeBA’s Committee for Hospitals and Institutions: A reflection about his history

Partiendo de las teorizaciones de autores psicoanalíticos acerca de la inserción de los sujetos en las Instituciones, se hace un relato de la historia de los nueve años de existencia de la Comisión de Hospitales e Instituciones en el seno de APdeBA. Se destaca la labor realizada en Docencia y Supervisión, y se citan trabajos científicos producidos por los miembros participantes. Se subraya la necesidad de los aportes interdisciplinarios entre Psicoanálisis y Medicina