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1.
Biochem Biophys Res Commun ; 276(2): 534-8, 2000 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-11027509

RESUMEN

Baicalin (BA) is a flavonoid compound purified from medicinal plant Scutellaria baicalensis Georgi and has been shown to possess anti-inflammatory and anti-HIV-1 activities. In an effort to elucidate the mechanism of the anti-inflammatory effect of BA, we recently found that this flavonoid compound was able to form complexes with selected chemokines and attenuated their capacity to bind and activate receptors on the cell surface. These observations prompted us to investigate whether BA could inhibit HIV-1 infection by interfering with viral entry, a process known to involve interaction between HIV-1 envelope proteins and the cellular CD4 and chemokine receptors. We found that BA at the noncytotoxic concentrations, inhibited both T cell tropic (X4) and monocyte tropic (R5) HIV-1 Env protein mediated fusion with cells expressing CD4/CXCR4 or CD4/CCR5. Furthermore, presence of BA at the initial stage of HIV-1 viral adsorption blocked the replication of HIV-1 early strong stop DNA in cells. Since BA did not inhibit binding of HIV-1 gp120 to CD4, we propose that BA may interfere with the interaction of HIV-1 Env with chemokine coreceptors and block HIV-1 entry of target cells. Therefore, BA can be used as a basis for developing novel anti-HIV-1 agents.


Asunto(s)
Antivirales/farmacología , Flavonoides/farmacología , VIH-1/efectos de los fármacos , Antígenos CD4/metabolismo , Proteína gp120 de Envoltorio del VIH/metabolismo , Proteína gp120 de Envoltorio del VIH/fisiología , VIH-1/fisiología , Humanos , Células Tumorales Cultivadas
2.
J Exp Med ; 180(3): 1047-57, 1994 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-8064224

RESUMEN

Transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 2 can reversibly inhibit the proliferation of hematopoietic progenitor cells in vivo, leading us to hypothesize that such quiescent progenitors might be more resistant to high doses of cell cycle active chemotherapeutic drugs, thereby allowing dose intensification of such agents. Initial studies showed that whereas administration of TGF-beta 1 or TGF-beta 2 did not prevent death in normal mice treated with high doses of 5-fluorouracil (5-FU), those mice that received TGF-beta 2 did exhibit the beginning of a hematologic recovery by day 11 after administration of 5-FU, and were preferentially rescued by a suboptimal number of transplanted bone marrow cells. Subsequently, it was found that the administration of TGF-beta 2 protected recovering progenitor cells from high concentrations of 5-FU in vitro. This protection coincided with the finding that significantly more progenitors for colony-forming unit-culture (CFU-c) and CFU-granulocyte, erythroid, megakaryocyte, macrophage (GEMM) were removed from S-phase by TGF-beta in mice undergoing hematopoietic recovery than in normal mice. Further studies showed that the administration of TGF-beta protected up to 90% of these mice undergoing hematologic recovery from a rechallenge in vivo with high dose 5-FU, while survival in mice not given TGF-beta was < 40%. Pretreatment of mice with TGF-beta 1 or TGF-beta 2 also protected 70-80% of mice from lethal doses of the noncycle active chemotherapeutic drug, doxorubicin hydrochloride (DXR). These results demonstrate that TGF-beta can protect mice from both the lethal hematopoietic toxicity of 5-FU, as well as the nonhematopoietic toxicity of DXR. This report thus shows that a negative regulator of hematopoiesis can be successfully used systemically to mediate chemoprotection in vivo.


Asunto(s)
Doxorrubicina/toxicidad , Fluorouracilo/toxicidad , Factor de Crecimiento Transformador beta/farmacología , Animales , Médula Ósea/efectos de los fármacos , Trasplante de Médula Ósea , División Celular/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/fisiología , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes/farmacología
3.
Cell Mol Biol Res ; 39(2): 119-24, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-7693133

RESUMEN

Baicalin (BA), (formulated as 7-D-glucuronic acid-5,6-dihydroxy-flavone), was purified from the plant Scutellaria Baicalensis Georgi. It has been used as a traditional Chinese herbal medicine. The inhibitory effect of BA against human immunodeficiency virus (HIV-1) infection and replication has been studied in vitro. The compound inhibits HIV-1 infection and replication as measured by: (1) a quantitative focal syncytium formation on CEM-ss monolayer cells; and (2) HIV-1 specific core antigen p24 expression and retroviral reverse transcriptase (RT) activity in the HIV-1-infected H9 cells. We have further demonstrated that the enzymatic activity of purified recombinant HIV-1/RT was inhibited by BA. In addition to lymphoid cell lines, the anti-HIV-1 activity of BA was also observed in cultures of primary human peripheral blood mononuclear cells infected with HIV-1 in vitro. Neither cytotoxic nor cytostatic effects on the indicator cells were found under the assay condition. This data suggests that BA may serve as a useful drug for the treatment and prevention of HIV infections.


Asunto(s)
Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Flavonoides/farmacología , VIH-1/efectos de los fármacos , Linfocitos T CD4-Positivos/microbiología , Células Cultivadas , Efecto Citopatogénico Viral/efectos de los fármacos , Proteína p24 del Núcleo del VIH/biosíntesis , Transcriptasa Inversa del VIH , VIH-1/fisiología , Humanos , Leucocitos Mononucleares/microbiología , Inhibidores de la Transcriptasa Inversa , Replicación Viral/efectos de los fármacos
4.
J Infect Dis ; 165(3): 433-7, 1992 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1371535

RESUMEN

The ability of baicalin (7-glucuronic acid, 5,6-dihydroxyflavone), a flavonoid compound purified from the Chinese medicinal herb, Scutellaria baicalensis georgi, to inhibit human T cell leukemia virus type I (HTLV-I) was examined. Baicalin produced concentration-dependent inhibition of HTLV-I replication in productively infected T and B cells. Moreover, baicalin treatment selectively reduced the detectable levels of HTLV-I p19 gag protein in infected cells by greater than 70% at concentrations that produced insignificant effects on total cellular protein and DNA synthesis with no loss in cell viability. Resistance to HTLV-I infection and virus-mediated transformation was noted in uninfected peripheral blood lymphocytes pretreated with baicalin before cocultivation with lethally irradiated chronically infected cells. Baicalin inhibited reverse transcriptase activity in HTLV-I-infected cells as well as the activity of purified reverse transcriptase from Moloney murine leukemia virus and Rous-associated virus type 2. These results suggest that baicalin may be a potential therapeutic agent against HTLV-I-associated T cell diseases.


Asunto(s)
Antiinfecciosos/farmacología , Linfocitos B/microbiología , Flavonoides/farmacología , Virus Linfotrópico T Tipo 1 Humano/efectos de los fármacos , Linfocitos T/microbiología , Línea Celular , Células Cultivadas , Medicamentos Herbarios Chinos/farmacología , Regulación Viral de la Expresión Génica/efectos de los fármacos , Productos del Gen gag/antagonistas & inhibidores , Antígenos HTLV-I/efectos de los fármacos , Virus Linfotrópico T Tipo 1 Humano/enzimología , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Proteínas Oncogénicas de Retroviridae/antagonistas & inhibidores , Inhibidores de la Transcriptasa Inversa , Replicación Viral/efectos de los fármacos , Productos del Gen gag del Virus de la Inmunodeficiencia Humana
5.
J Biol Response Mod ; 5(1): 85-107, 1986 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-3514800

RESUMEN

Six lymphoid human interleukin-2s (nIL-2s) [four from peripheral blood mononuclear cells (PBMC) and two from JURKAT cells] and six recombinant IL-2s (rIL-2s) were obtained for comparative evaluation. The main issues addressed were possible differences among the preparations in potency in T cell growth assays and other functional assays, and the possible presence of other cytokine activities or contaminants. Each preparation was assigned a standardized IL-2 activity in reference units (RU) by comparing its T cell growth promoting activity against the Biological Response Modifiers Program IL-2 (JURKAT) reference reagent. Relative to the IL-2 unitage indicated by the suppliers, the RU varied from 110-fold less to 38.5-fold more for the various preparations. Two nIL-2s and two rIL-2s contained significant levels of endotoxin. One nIL-2 contained low levels of both alpha and gamma interferon (IFN), and one nIL-2 had a high level of gamma IFN. All other IL-2s were negative for IFN activity. All IL-2 preparations significantly augmented human natural killer (NK) activity, although the amount of RU required varied from 0.1 to 50 RU. Four nIL-2s and three rIL-2s induced human PBMC to produce gamma IFN, whereas two nIL-2s and one rIL2 did not. All nIL-2s had substantial amounts of B cell growth factor activity, whereas none of the rIL-2s consistently displayed this activity. All IL-2s stimulated the tritiated thymidine [3H]TdR incorporation of human PBMC in the absence of other stimuli, in addition to augmenting the response to mitogen or alloantigens. Some nILs and IL-2s had effects on human monocytes such as inhibiting migration, inducing cytotoxic or growth inhibitory activity against tumor cells, and causing changes in cell surface markers. The IL-2s were also tested for activity in vitro and in vivo in mice. Although there was a 12-fold variation in activity among the preparations, all but one of the IL-2s showed augmentation of the mixed lymphocyte reaction activity and all IL-2s tested stimulated macrophage cytotoxicity in vitro. All IL-2s tested enhanced the mixed lymphocyte-allogeneic tumor cell reaction resulting in greater production of cytotoxic T cells. However, significant quantitative differences in potency were evident among the various IL-2 preparations, especially the nIL-2s. Only very high doses of IL-2 (intraperitoneal injection of 100,000 RU/animal) induced in vivo augmentation of splenic or peritoneal NK cells, although all IL-2s tested increased NK activity against tumor target cells in vitro with substantially lower doses (10-100 RU/ml).(ABSTRACT TRUNCATED AT 400 WORDS)


Asunto(s)
Interleucina-2/aislamiento & purificación , Animales , Bioensayo , Evaluación Preclínica de Medicamentos , Humanos , Técnicas In Vitro , Interleucina-2/fisiología , Activación de Linfocitos , Linfocitos/inmunología , Ratones , Estándares de Referencia , Linfocitos T/inmunología
6.
Cell Immunol ; 92(1): 14-21, 1985 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-3935331

RESUMEN

The ability to grow a clone of the cell line, MLA144, which is a constitutive producer of interleukin 2 (IL-2), in serum-free medium permitted the study of the direct effect of various agents on cell growth and IL-2 production in a homogeneous population. Bovine serum albumin (BSA) at 4 mg/ml was optimal for cell growth and IL-2 production. Selenium at 10 ng/ml enhanced IL-2 production nearly twofold and lithium at 42 ng/ml also enhanced IL-2 production by nearly twofold. Neither compound at these levels altered cellular proliferation. Two other compounds, iron and zinc, known to be associated with cellular proliferation and/or immunoregulation did not alter IL-2 production. Catalase or horseradish peroxidase was able to substitute for BSA and maintain the long-term growth of the MLA144 clone with only a 30% decrease in the rate of cellular proliferation and a 50% decrease in IL-2 production compared to cells maintained in the serum-free formulation with BSA. Addition of 0.5 mg of BSA to the catalase serum-free formulation increased the production of IL-2 to 70% of that of cells cultured in the BSA-containing serum-free formulation. The catalase-containing serum-free formulation has the advantage of consisting of only three proteins, catalase, insulin, and transferrin, at a very low protein content. The catalase-containing serum-free medium also supported the long-term growth of a human T-cell line, HSB-2.


Asunto(s)
Fenómenos Fisiológicos Sanguíneos , Medios de Cultivo/farmacología , Interleucina-2/metabolismo , Linfocitos T/metabolismo , Animales , Callitrichinae , Catalasa/farmacología , Línea Celular , Interleucina-2/biosíntesis , Hierro/farmacología , Litio/farmacología , Activación de Linfocitos/efectos de los fármacos , Selenio/farmacología , Albúmina Sérica Bovina/farmacología , Linfocitos T/inmunología , Zinc/farmacología
7.
J Natl Cancer Inst ; 71(6): 1189-92, 1983 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-6606727

RESUMEN

Necessary for growth and differentiation in many normal tissues and capable of inducing differentiation in human promyelocytic cell lines, retinoids were the subject of this study. Specifically, effects of 13-cis-retinoic acid and 13-trans-retinoic acid on the growth of normal human bone marrow cells in soft-agar system were studied. Both short-term incubation and continuous exposure to retinoic acid caused a decreased number of granulocyte colonies and an increased cluster-to-colony ratio. This effect was concentration-dependent. Examination of specimens stained with Wright-Giemsa or nitro blue tetrazolium stains showed a progressive increase in the percentage of immature granulocytic precursors with increasing concentrations of retinoic acid. No effect of retinoic acid was seen on a number of human tumor cell lines. Retinoic acid blocked both differentiation and proliferation and appeared to do so by specific, noncytotoxic mechanisms in normal human bone marrow cells.


Asunto(s)
Médula Ósea/efectos de los fármacos , Factores Estimulantes de Colonias/farmacología , Tretinoina/farmacología , Células de la Médula Ósea , Linfoma de Burkitt/tratamiento farmacológico , División Celular/efectos de los fármacos , Línea Celular , Células Clonales/citología , Células Clonales/efectos de los fármacos , Ensayo de Unidades Formadoras de Colonias , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Humanos , Leucemia Mieloide/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Mieloma Múltiple/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico
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