Anti-inflammatory activity of substituted 1,3,4-oxadiazoles

Various 2-(4-biphenoxymethyl)-5-arylamino-1,3,4-oxadiazoles were synthesized by cyclization of the corresponding 1-(4-biphenoxyacetyl)-4-substituted thiosemicarbazides. These compounds were characterized by their elemental analyses and infrared, mass, and nuclear magnetic resonance spectral data. All substituted thiosemicarbazides (100 mg/kg, ip) and cyclized substituted oxadiazoles (100 mg/kg, ip) possessed anti-inflammatory activity, as reflected by their ability to provide protection against carrageenin-induced edema in the rat paw which ranged from 28 to 68% and 36 to 76%, respectively. Cyclization of the substituted thiosemicarbazides, in general, resulted in an increase in the anti-inflammatory activity of their corresponding substituted oxadiazoles, with the exception of those containing 2,4-dimethyl and 3,4-dimethyl substituents in their molecular structure. Hydrocortisone (10 mg/kg, ip) and oxyphenbutazone (40 mg/kg, ip) were used as the standard reference drugs and these provided 45 and 53% protection, respectively. All compounds (1 mM) possessed antiproteolytic activity and the in vitro inhibition of trypsin-induced hydrolysis of bovine serum albumin ranged from 13 to 75% for substituted thiosemicarbazides and 39 to 70% for substituted oxadiazoles. There was no relationship between the anti-inflammatory activity of substituted thiosemicarbazides and substituted oxadiazoles and their antiproteolytic effectiveness. The low toxicity of these compounds was reflected by their high approximate LD50 values, ranging from 500 to 1000 mg/kg.     

Preserved vision in a case of morning glory syndrome: some pertinent questions

Morning glory syndrome, an unusual developmental anomaly of the optic nerve head, presenting with funnelled enlargement of the disc with a white dot in the centre and a peripheral vascular pattern along the disc margin, with features of typical entry and exit of retinal vessels on the optic nerve head and exceptionally good vision in the involved eye with old traumatic retinal detachment in the other, in a young Indian girl is described here for its rarity and indifferent clinical presentation. Various factors in its pathogenesis are postulated.     

Competitive control of the self-renewing T cell repertoire

We develop a mathematical model for the self-renewing part of the T cell repertoire. Assuming that self-renewing T cells have to be stimulated by immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting cells, we derive a model of T cell growth in which competition for MHC-peptide complexes limits T cell clone sizes and regulates the total number of self-renewing T cells in the animal. We show that for a sufficient diversity and/or degree of cross-reactivity, the total T cell number hardly depends upon the diversity of the T cell repertoire or the diversity of the set of presented peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity, steady-state total T cell numbers may be limited by the diversity of the T cells. This provides a possible explanation for the limited repertoire expansion in some, but not all, mouse T cell re-constitution experiments. We suggest that the competitive interactions described by our model underlie the normal T cells numbers observed in transgenic mice, germ-free mice and various knockout mice.      

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

Correlation Between Monoamine Oxidase Inhibitors and Anticonvulsants

Monoamine oxidase inhibitory and anticonvulsant properties of 2-substituted styryl-6-bromo-3-(4-ethylbenzoate/4 benzhydrazide)-4-quinazoles are studied. All styryl quinazolone esters except compound number 9 exhibited monoamine oxidase inhibitory properties during oxidative deamination of kynuramine. Corresponding hydrazides were found to have relatively higher activity. All these quinazolones were able to protect against pentylenetetrazol induced seizures. These observations in general do not prove that monoamine oxidase inhibitory properties represent the biochemical basis for the anticonvulsant activity of these compounds.