RESUMO
Before 1978 in China, the economic institutions for agriculture and industry operated essentially under a centrally planned system. The reasons for a change toward a more market-oriented economy and the key elements of economic reform are discussed. Today the major issues being deliberated by the leading economic officials include reform of the price system, the administrative structure of state-owned enterprises, the banking system and macroeconomic control mechanisms, and foreign trade and investment.
RESUMO
Dibenz[b,f][1,4]oxazepin-11(10H)-ones (III), pyrido[2,3-b][1,4]benzoxazepin-6(5H)-ones (IV), and pyrido[2,3-b]- [1,5]benzoxazepin-5(6H)-ones (V) were found to inhibit human immunodeficiency virus type 1 reverse transcriptase with IC50 values as low as 19 nM. A-ring substitution has a profound effect on activity, with appropriate substituents at the positions ortho and para to the lactam nitrogen providing dramatically enhanced potency. Substitution in the C-ring is generally neutral or detrimental to activity. Although a C-ring amino substituent at the position meta to the lactam carbonyl is generally beneficial to activity, it has essentially no effect when the A-ring is optimally substituted. Like the dipyridodiazepinone nevirapine, compounds III-V are specific for HIV-1 RT, exhibiting no inhibitory activity against HIV-2 RT or other virial reverse transcriptase enzymes.
Assuntos
Dibenzoxazepinas/farmacologia , HIV-1/enzimologia , Inibidores da Transcriptase Reversa , Dibenzoxazepinas/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Proteínas Recombinantes/antagonistas & inibidoresRESUMO
Two brothers with a painful neuropathy as a component of late-onset GM2 gangliosidosis of the Sandhoff type are presented. A dramatic response of the severe dysesthesias to amitriptyline and gabapentin is described. Symptomatic sensory neuropathy may be a component of late-onset GM2 gangliosidosis.
Assuntos
Aminas , Ácidos Cicloexanocarboxílicos , Gangliosidoses GM2/complicações , Gangliosidoses GM2/diagnóstico , Parestesia/etiologia , Doença de Sandhoff/complicações , Ácido gama-Aminobutírico , Acetatos/uso terapêutico , Adolescente , Amitriptilina/uso terapêutico , Analgésicos/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Quimioterapia Combinada , Potenciais Somatossensoriais Evocados , Pé/fisiopatologia , Gabapentina , Humanos , Masculino , Parestesia/tratamento farmacológico , Doença de Sandhoff/tratamento farmacológico , Resultado do TratamentoRESUMO
The proteinase encoded by human immunodeficiency virus type 1 (HIV-1) cleaves peptide substrates of sequences derived from processing sites in HIV-1 gag-pol polypeptide. Based on this cleavage, assays that utilize HPLC to measure activity of HIV-1 proteinase are reported herein. In the assay first described, a baseline separation of unlabeled substrate and products is achieved with a run time of 10 min and UV detection. Enzyme concentrations as low as 1 nM, which is the lowest reported for an assay employing underivatized peptide substrate, are attained. Even more powerful, versatile and sensitive, a second method that takes advantage of a peptide substrate labeled at its N-terminus with the fluorescein derivative is described as well. Because of the fluorescein label, this method offers several superior features, including very fast analysis of substrate and product in less than 3 min and fluorescence detection which provides essentially total freedom from interference. Synthesis of fluorescein-labeled peptide substrate is accomplished by solid-phase peptide synthesis.