Indoline derivatives as 5-HT(2C) receptor agonists.

A series of 1-(1-indolinyl)-2-propylamines was synthesised and evaluated as 5-HT(2C) receptor agonists for the treatment of obesity. The general methods of synthesis of the precursor indoles are described. The functional efficacy and radioligand binding data for all of the compounds at 5-HT(2) receptor subtypes are reported. A number of compounds were found to reduce food intake in rats after oral administration.

Characterization of iodoacetate-mediated neurotoxicity in vitro using primary cultures of rat cerebellar granule cells.

The neuroprotective efficacy of antioxidant molecules against iodoacetate (IAA) neurotoxicity in rat cerebellar granule cell (CGC) cultures was investigated. Transient exposure to IAA caused a concentration-dependent decrease in cell viability (ED50 = 9.8 microM). Dizocilpine maleate (MK-801), and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide (NBQX), failed to prevent IAA toxicity. Certain antioxidant molecules were shown to be neuroprotective against IAA when combined with MK-801 but were ineffective when administered alone. (S)-(-)-Trolox, butylated hydroxytoluene (BHT), and U-83836E exhibited EC50 values of 78, 5.9, and 0.25 microM, respectively, in the presence of 10 microM MK-801. IAA also induced an increase in intracellular oxidative stress, which was quenched by the antioxidants (in the presence of MK-801) in cultures loaded with the oxidant sensitive dye 2'7'-dichlorodihydrofluorescein diacetate (DCFH-DA).

Analytical description of backscattered states of polarization in polarization optical time-domain reflectometry measurements on uniformly twisted linearly birefringent optical fiber.

We present a detailed derivation of the locus of Rayleigh backscattered states of polarization for polarization optical time domain reflectometry in uniformly twisted optical fiber with intrinsic linear birefringence. The locus is algebraically a quartic whose topology is determined by the relative orientation on the Poincaré sphere of the input SOP and the effective birefringence vector. We present an analysis that indicates how experimental data may be interpreted, through geometric parameters of the locus, for evaluating the fiber parameters. The analysis also indicates the minimum number of experimental data points required for meaningful values for the fiber parameters to be obtained.

RSC-SCI--tenth medicinal chemistry symposium. 5-8 September 1999, Churchill College, Cambridge, UK.

This meeting was part of a biennial series focusing upon topics at the forefront of medicinal chemistry. There was no single therapeutic focus for the meeting, but the 24 lectures were spread between various themes: enzyme inhibitors; drug-receptor/ion channel interactions; enabling technologies; and, new topics in drug research. Several of the lectures featured structure-activity relationships of new drugs, outlining the rationale for the selection of drug candidates. It was clear that many pharmaceutical companies now routinely employ in vivo studies of distribution and pharmacokinetics early in the drug discovery process, thereby adding to the traditional criteria of affinity, selectivity and in vivo effect when potential drugs are selected for development. Likelihood of success during later clinical investigation phases is thereby enhanced.

Speech therapy and elderly people: a study of therapists' attitudes.

This paper describes a survey of the attitudes of speech therapists towards working with elderly people. The findings are compared to those of similar studies of medical students and physiotherapists. A positive orientation towards the elderly was found to relate to the time spent working with older people, but not to the time since qualifying. The results indicate a marked increase in the amount of teaching and clinical experience received by speech therapy undergraduates, and demonstrates that training might not be influencing therapists' attitudes to the elderly. The implications of these findings on the services for the elderly are discussed.

Hemoglobin H disease and mental retardation: a new syndrome or a remarkable coincidence?

Each of three families of northern European origin contains a mentally retarded son with hemoglobin H (Hb H) disease. One parent is a carrier of mild alpha-thalassemia and the other is normal, suggesting that this form of Hb H disease results from the interaction between an inherited defect of alpha-chain production and one member of the pair in chromosome 16 and a new mutation on the other. Restriction-enzyme analysis indicated that the new mutation was not the same in the other three patients, and demonstrated at least two hitherto undescribed lesions involving the alpha-globin gene cluster. Unless the association between the Hb H disease and mental retardation is fortuitous, the new mutations may also be related to the development changes in these children. Since the mutations only came to light because there was concurrent inheritance of an additional alpha-thalassemia determinant, this type of mutation of chromosome 16 may have been overlooked in other mentally retarded patients.