RESUMEN
The course of Flexner dysentery has been analysed in 110 fatal cases. They died in St. Petersburg in 1994. Fatal outcomes occurred more frequently in the elderly and unsuccessful subjects. Hospitalization in many cases was late. Dysentery ran often in the presence of concomitant disorders (cardiovascular, alcoholic, alimentary) and was complicated with shock, pneumonia, peritonitis. At autopsy, there were severe catarrhal, fibrinolytic, flegmonous, hemorrhagic, ulcerative and necrotic lesions of both large and small intestine.
Asunto(s)
Disentería/etiología , Adulto , Anciano , Anciano de 80 o más Años , Disentería/mortalidad , Disentería/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Federación de Rusia/epidemiología , Tasa de SupervivenciaRESUMEN
To investigate the mechanism of action of the 22-amino-acid HIV fusion peptide on HIV infection, we studied its influence on virus adsorption and HIV-induced syncytium formation. The effect of the peptide preparations on the synthesis of viral antigens in HIV-infected cell cultures was determined by antigen capture assay, and the inhibition of proviral DNA synthesis was detected by hybridization with a HIV-specific oligonucleotide probe after PCR amplification. Fusion peptides inhibited HIV-induced syncytium formation and antigen production in lytic infected cells, and this effect was increased in conjugation with bovine serum albumin or with synthetic net-charged polymer by its C-terminus. The association of peptide with carrier by N-terminus, or with positive-charged polymer or gelatin completely abolished its effect on HIV infection. No peptide preparations influenced HIV-1 chronically infected cells. Because peptide preparations blocked the HIV-specific DNA synthesis 2 hr after infection without influencing virus adsorption and reverse transcription, we concluded that the block of infection occurred during the penetration of virions through the cell membrane. On the basis of results obtained we propose that our peptide preparations could be used for anti-HIV chemotherapy. The possibility of the existence of receptors for gp41 N-terminal region on target cell membrane is discussed.
Asunto(s)
Antivirales/farmacología , Proteína gp41 de Envoltorio del VIH/farmacología , VIH-1/fisiología , Fragmentos de Péptidos/farmacología , Secuencia de Aminoácidos , Especificidad de Anticuerpos , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/microbiología , Fusión Celular/efectos de los fármacos , ADN Viral/análisis , Relación Dosis-Respuesta a Droga , Portadores de Fármacos , Anticuerpos Anti-VIH/inmunología , Proteína gp41 de Envoltorio del VIH/inmunología , Proteína gp41 de Envoltorio del VIH/ultraestructura , Transcriptasa Inversa del VIH , VIH-1/efectos de los fármacos , VIH-1/crecimiento & desarrollo , Humanos , Datos de Secuencia Molecular , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/inmunología , Reacción en Cadena de la Polimerasa , ADN Polimerasa Dirigida por ARN/análisis , Replicación Viral/efectos de los fármacosAsunto(s)
Agregación Celular/efectos de los fármacos , Disulfuros/farmacología , VIH/efectos de los fármacos , Integrinas/antagonistas & inhibidores , Linfocitos/fisiología , Extractos Vegetales/farmacología , Linfocitos/microbiología , Agregación Plaquetaria/efectos de los fármacos , Células Madre/fisiología , SulfóxidosRESUMEN
5'-Phosphites (5'-hydrogenphosphonates) of 2',3'-dideoxynucleosides (T, A, G, C) were synthesized and studied as inhibitors of human immunodeficiency virus type 1 (HIV-1) in MT4 and CEM13 cell cultures. It was shown that all 5'-phosphites effectively inhibit the production of viral antigens and protect cells from the cytotoxic effect of HIV infection. 5'-Phosphites were more active antiviral compounds than the corresponding nucleosides.
Asunto(s)
Antivirales/farmacología , Didesoxinucleósidos/farmacología , VIH-1/fisiología , Nucleótidos de Timina/farmacología , Replicación Viral/efectos de los fármacos , Zidovudina/análogos & derivados , Células Cultivadas , Didesoxinucleótidos , Ensayo de Inmunoadsorción Enzimática , Antígenos VIH/análisis , Zidovudina/metabolismo , Zidovudina/farmacologíaRESUMEN
Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene-9-oxide, isolated from extracts of garlic (Allium sativum) has been previously shown to inhibit platelet aggregation by inactivating allosterically the platelet integrin, GP IIb/IIIa. The structural and functional similarity of integrins led the authors to suggest that ajoene may also inhibit adhesive interactions and fusion of leukocytes. Synthetic stereoisomers of ajoene synthesized by the authors exhibited equal antiaggregatory activities (IC100 approximately 50 microM for platelets; IC100 approximately 10 microM for fMLP-stimulated neutrophils). Racemic ajoene inhibited the fusion of H9 cells with HIV-infected H9:RF cells (IC50 approximately 45 microM; 16 h of incubation) and also exhibited a degree of antiviral activity (IC50 approximately 5 microM as assessed by inhibition of HIV-1/CEM/Lav 1 Bru replication in CEM13 cells; m. o. i. 0.1; 72 h). A considerable increase in the latter became evident when the compound was administered in aliquots of 50 microM per 12 h of incubation (inhibition by 30%; total concentration 0.25 microM; 72 h).(ABSTRACT TRUNCATED AT 250 WORDS)