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Ingestión de Alimentos , Gota/epidemiología , Gota/prevención & control , Prunus , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: It is currently recommended that diet of pregnant mothers contain 200-300 mg DHA/day. Aim. To determine whether DHA supplementation during pregnancy and lactation affects infants' immune response. METHODS: 60 women in ≥3rd pregnancy studied; 30 randomly assigned to receive DHA 400 mg/day from 12th week gestation until 4 months postpartum. From breast-fed infants, blood obtained for anti-HBs antibodies, immunoglobulins, lymphocyte subset phenotyping, and intracellular cytokine production. RESULTS: CD4+ lymphocytes did not differ between groups, but CD4CD45RA/CD4 (naïve cells) significantly higher in infants in DHA+ group. Proportion of CD4 and CD8 cells producing IFN(γ) significantly lower in DHA+ group, with no differences in proportion of IL4-producing cells. Immunoglobulins and anti-HBs levels did not differ between groups. CONCLUSIONS: In infants of mothers receiving DHA supplementation, a higher percentage of CD4 naïve cells and decreased CD4 and CD8 IFN(γ) production is compatible with attenuation of a proinflammatory response.
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Lactancia Materna , Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/inmunología , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Lactancia/inmunología , Adulto , Ácidos Docosahexaenoicos/sangre , Femenino , Humanos , Lactante , Subgrupos Linfocitarios/inmunología , Embarazo , Adulto JovenRESUMEN
Several quinones have been found to be effective in the treatment of some forms of cancer; however, their cumulative heart toxicity limits their use. The cannabinoid quinone HU-331 [3S,4R-p-benzoquinone-3-hydroxy-2-p-mentha-(1,8)-dien-3-yl-5-pentyl] is highly effective against tumor xenografts in nude mice. We report now a comparison of the anticancer activity of HU-331 and its cardiotoxicity with those of doxorubicin in vivo. General toxicity was assayed in Sabra, nude and SCID-NOD mice. The anticancer activity in vivo was assessed by measurement of the tumors with an external caliper in HT-29 and Raji tumor-bearing mice and by weighing the excised tumors. Left ventricular function was evaluated with transthoracic echocardiography. Myelotoxicity was evaluated by blood cell count. Cardiac troponin T (cTnT) plasma levels were determined by immunoassay. HU-331 was found to be much less cardiotoxic than doxorubicin. The control and the HU-331-treated groups gained weight, whereas the doxorubicin-treated group lost weight during the study. In HT-29 colon carcinoma, the tumor weight in the HU-331-treated group was 54% smaller than in the control group and 30% smaller than in the doxorubicin-treated group. In Raji lymphoma, the tumor weight in the HU-331-treated group was 65% smaller than in the control group and 33% smaller than in the doxorubicin-treated group. In contrast to doxorubicin, HU-331 did not generate reactive oxygen species in mice hearts (measured by protein carbonylation levels and malondialdehyde levels). In vivo, HU-331 was more active and less toxic than doxorubicin and thus it has a high potential for development as a new anticancer drug.
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Cannabidiol/análogos & derivados , Doxorrubicina/farmacología , Corazón/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Recuento de Células Sanguíneas , Peso Corporal/efectos de los fármacos , Cannabidiol/química , Cannabidiol/farmacología , Línea Celular Tumoral , Doxorrubicina/química , Ecocardiografía , Células HT29 , Corazón/fisiopatología , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones Endogámicos , Ratones Desnudos , Ratones SCID , Estructura Molecular , Miocardio/metabolismo , Miocardio/patología , Neoplasias/sangre , Neoplasias/patología , Carbonilación Proteica/efectos de los fármacos , Troponina T/sangre , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Anthracyclines, a large group of quinonoid compounds, are used to treat some forms of cancer. Although highly effective in cancer therapy, the mechanism of action of these compounds is not specific; they act on cancer and other cells by numerous mechanisms. A new anticancer quinone (HU-331) was synthesized from cannabidiol. It shows significant high efficacy against human cancer cell lines in vitro and against in vivo tumor grafts in nude mice. In this study, we investigated its mode of action and present evidence on its unique mechanism. HU-331 does not cause cancer cell cycle arrest, cell apoptosis, or caspase activation. HU-331-caused cell death of human cancer cell lines is not mediated by reactive oxygen intermediates/species, as exposure to HU-331 failed to elicit the generation of reactive oxygen species. HU-331 inhibits DNA topoisomerase II even at nanomolar concentrations but has only a slight nonsignificant effect on DNA topoisomerase I action. The cannabinoid quinone HU-331 is a highly specific inhibitor of topoisomerase II, compared with most known anticancer quinones. It might represent a new potent anticancer drug.
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Antineoplásicos/química , Antineoplásicos/farmacología , Cannabidiol/análogos & derivados , Proteínas de Unión al ADN/antagonistas & inhibidores , Inhibidores de Topoisomerasa II , Antígenos de Neoplasias , Apoptosis/efectos de los fármacos , Cannabidiol/química , Cannabidiol/farmacología , Antagonistas de Receptores de Cannabinoides , Caspasa 3/metabolismo , Ciclo Celular/efectos de los fármacos , Roturas del ADN , ADN-Topoisomerasas de Tipo II , ADN de Neoplasias/química , ADN de Neoplasias/genética , Células HT29 , Humanos , Células Jurkat , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Conformación de Ácido Nucleico , Especies Reactivas de Oxígeno/metabolismo , Receptores de Cannabinoides/metabolismoRESUMEN
Recent findings on the inhibition of angiogenesis and vascular endothelial cell proliferation by anthracycline antibiotics, which contain a quinone moiety, make this type of compound a very promising lead in cancer research/therapy. We have reported that a new cannabinoid anticancer quinone, cannabidiol hydroxyquinone (HU-331), is highly effective against tumor xenografts in nude mice. For evaluation of the antiangiogenic action of cannabinoid quinones, collagen-embedded rat aortic ring assay was used. The ability of cannabinoids to cause endothelial cell apoptosis was assayed by TUNEL staining and flow cytometry analysis. To examine the genes and pathways targeted by HU-331 in vascular endothelial cells, human cDNA microarrays and polymerase chain reaction were used. Immunostaining with anti-CD31 of tumors grown in nude mice served to indicate inhibition of tumor angiogenesis. HU-331 was found to be strongly antiangiogenic, significantly inhibiting angiogenesis at concentrations as low as 300 nM. HU-331 inhibited angiogenesis by directly inducing apoptosis of vascular endothelial cells without changing the expression of pro- and antiangiogenic cytokines and their receptors. A significant decrease in the total area occupied by vessels in HU-331-treated tumors was also observed. These data lead us to consider HU-331 to have high potential as a new antiangiogenic and anticancer drug.
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Benzoquinonas/farmacología , Cannabidiol/análogos & derivados , Cannabinoides/farmacología , Células Endoteliales/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , Aorta/crecimiento & desarrollo , Apoptosis/efectos de los fármacos , Cannabidiol/farmacología , Bovinos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Endoteliales/citología , Células Endoteliales/fisiología , Expresión Génica/genética , Células HT29 , Humanos , Inmunohistoquímica , Técnicas In Vitro , Ratones , Ratones Desnudos , Neovascularización Patológica/metabolismo , Neovascularización Patológica/prevención & control , Neovascularización Fisiológica/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Ratas , Factor A de Crecimiento Endotelial Vascular/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: Systemic lupus erythematosus is a multisystem disease with many clinical variations, including renal involvement. Our aim was to determine whether lupus nephritis (LN) has a specific seasonality. METHODS: Reports of renal biopsies performed from 1990 to 2002 were reviewed. Three hundred and seventy-three patients with class II, III, IV, and V LN were identified. Using the modified WHO classification of LN, diagnoses were tabulated and the seasonality (season of diagnosis) of LN was statistically analyzed. RESULTS: Class IV LN was detected in 179 patients (48%), class II in 63 patients (16.9%), class III in 73 patients (19.57%), and class V in 74 patients (19.9%). No difference could be detected in the number of patients diagnosed in each season when all 373 patients were analyzed as one group. The number of patients with class IV LN was higher during summer and fall than during the winter and spring. In contrast, a higher number of patients with class V LN were observed during the winter and spring seasons than during the summer and fall seasons. The percentage of patients with class V LN was significantly higher during winter and spring than during summer and fall. A similar, though non-significant, trend was seen for class III LN. A striking parallelism was found between the month of occurrence of class III and class V LN. The monthly distribution of the percentage of patients in each month with class III and V LN showed a significant correlation. The monthly distribution of patients with class IV LN was different from those with either class III or V LN. CONCLUSION: We found that the prevalence of class V LN was significantly higher and that of class III LN non-significantly higher in winter and spring. Parallelism between the monthly occurrences of class III and class V may suggest a common trigger. Analysis of the seasonality of LN may contribute to the understanding of the pathogenesis of LN, which may be multifactorial, as the different classes of LN represent different types of glomerular injury. Further studies are needed to clarify this potentially important observation.
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Nefritis Lúpica/epidemiología , Estaciones del Año , Adolescente , Adulto , Anciano , Biopsia , Niño , Femenino , Humanos , Nefritis Lúpica/patología , Nefritis Lúpica/fisiopatología , Masculino , Persona de Mediana Edad , New Jersey/epidemiología , New York/epidemiología , Prevalencia , Índice de Severidad de la EnfermedadRESUMEN
Extract: Seasonal variation has been shown in a number of rheumatic diseases (diseases involving the joints and related structures). The incidence of acute gouty attacks (an inflammatory arthritis) is highest in the spring. The onset or exacerbation of rheumatoid arthritis, the onset of Wegener's granulomatosis (chronic tissue inflammation and cellular clumping in the nasal passages, lungs and kidneys), anti-neutrophil cytoplasmic antibodies (ANCA) associated kidney inflammation (glomerulonephritis) and systemic vasculitis are all seen more commonly in the winter. There is a significant increase in the incidence of positive biopsies in giant cell arteritis (vascular inflammation of the temple) in late winter and autumn. In systemic lupus erythematosus (SLE, an autoimmune disease in which antibodies to self components are found in the blood stream and in tissues) there may be a tendency for different organs to be affected during different seasons. In SLE patients, there is an increased incidence of photosensitive skin rashes in the summer and of joint pain in the winter and spring. A significantly higher prevalence in the winter and spring was observed among SLE patients with class V lupus nephritis (LN, inflammation of the kidneys), as compared with the summer and fall. A similar trend was seen for seasonal variation of the percentage of class III lupus nephritis patients.
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Three cannabis constituents, cannabidiol (1), Delta(8)-tetrahydrocannabinol (3), and cannabinol (5), were oxidized to their respective para-quinones 2, 4, and 6. In the 1960s, the oxidized product 4 had been assigned a para-quinone structure, which was later modified to an ortho-quinone. To distinguish between the two possible quinone structures, a detailed NMR investigation was undertaken. The original para-quinone structure was confirmed. X-ray crystallography elucidated the structures of the crystalline 2 and 6. All three compounds displayed antiproliferative activity in several human cancer cell lines in vitro, and quinone 2 significantly reduced cancer growth of HT-29 cancer in nude mice.
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Antineoplásicos/síntesis química , Cannabinoides/síntesis química , Quinonas/síntesis química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Cannabinoides/química , Cannabinoides/farmacología , Línea Celular Tumoral , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Ratones , Ratones Desnudos , Quinonas/química , Quinonas/farmacología , Relación Estructura-Actividad , Trasplante HeterólogoRESUMEN
Lymphocytes (PBMC) obtained from blood of HIV-sera negative Ethiopian immigrants (ETH) were highly susceptible to HIV-1 infection in vitro with no need for stimulation by mitogens. As the HIV nef gene product has been shown to enhance viral replication in stimulated primary lymphocytes, we investigated in this work the role of Nef in viral replication in the ETH cells. Lymphocytes obtained from ETH individuals supported high replication of wild-type HIV-1 and low but significant replication level of the two deleted Nef mutants (encode truncated Nef proteins consisting only of either the first 35 or the first 86 amino acids of Nef). In contrast, no replication was observed in nonactivated cells obtained from non-ETH individuals. After activation of the PBMC from ETH individuals with PHA, replication of both wild-type strains and the two deleted Nef mutant viruses further increased. The CD4(+) T cells of ETH individuals exhibited elevated levels of the surface activation markers CD45RO and HLA-DR, compared with T cells derived from non-ETH group. Likewise, expression of the chemokine receptors CCR5 and CXCR4 on these cells was higher in the ETH group than in the non-ETH group. Replication of HIV-1 wild-type and the isogenic-deleted Nef mutants was significantly correlated with the proportion of ETH cells expressing CD45RO and the chemokine receptors. This study suggests that HIV-1 may respond differently to several activation states characteristic of T cells. One activation state, defined by chronically activated lymphocytes from ETH individuals, is permissive to the wild-type HIV-1 and, to a lesser degree, to the Nef mutants. Further activation of these cells by exogenous stimuli enhances replication of the virus. Our results support the notion that Nef enhances the basal level of T cell activation and consequently, viral replication.
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Productos del Gen nef/genética , Infecciones por VIH/inmunología , VIH-1/fisiología , Linfocitos T/inmunología , Replicación Viral , Células Cultivadas , Citometría de Flujo , Eliminación de Gen , Infecciones por VIH/sangre , Infecciones por VIH/virología , VIH-1/genética , Antígenos HLA-DR/análisis , Antígenos HLA-DR/biosíntesis , Humanos , Antígenos Comunes de Leucocito/análisis , Antígenos Comunes de Leucocito/biosíntesis , Leucocitos Mononucleares/inmunología , Receptores CCR5/biosíntesis , Receptores CXCR4/análisis , Receptores CXCR4/biosíntesis , Linfocitos T/virología , Productos del Gen nef del Virus de la Inmunodeficiencia HumanaRESUMEN
Stabilizing the carbon dioxide-induced component of climate change is an energy problem. Establishment of a course toward such stabilization will require the development within the coming decades of primary energy sources that do not emit carbon dioxide to the atmosphere, in addition to efforts to reduce end-use energy demand. Mid-century primary power requirements that are free of carbon dioxide emissions could be several times what we now derive from fossil fuels (approximately 10(13) watts), even with improvements in energy efficiency. Here we survey possible future energy sources, evaluated for their capability to supply massive amounts of carbon emission-free energy and for their potential for large-scale commercialization. Possible candidates for primary energy sources include terrestrial solar and wind energy, solar power satellites, biomass, nuclear fission, nuclear fusion, fission-fusion hybrids, and fossil fuels from which carbon has been sequestered. Non-primary power technologies that could contribute to climate stabilization include efficiency improvements, hydrogen production, storage and transport, superconducting global electric grids, and geoengineering. All of these approaches currently have severe deficiencies that limit their ability to stabilize global climate. We conclude that a broad range of intensive research and development is urgently needed to produce technological options that can allow both climate stabilization and economic development.
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Lines of Epstein-Barr virus (EBV)-transformed lymphoblastoid B-cells (B-LCLs) differ in the expression of surface CD4 glycoproteins. The aim of the present study was to correlate the expression of CD4 molecules on B-LCL cells with the synthesis of CD4 mRNA. RT-PCR assays were performed with oligonucleotide primers designed to detect mRNA corresponding to intracellular, transmembrane, or extracellular portions of the CD4 molecule. RT-PCR assays with all sets of primers were positive in T-cell populations, but were negative in various B-cell lymphoma lines. The majority of the LCLs established by EBV transfection of non-selected B-cells yielded positive results with at least some of the primer sets used for detection of CD4 mRNA. A significant positive correlation was found between the proportion of CD4+ cells in various B-LCLs and the concentration of CD4 mRNA. LCLs established from B-cells which synthesized various antibodies did not express CD4 molecules and either failed to synthesize CD4 mRNA or produced very low concentrations. These findings indicate that the expression of CD4 on B-LCLs is directly correlated with the concentration of CD4 mRNA synthesized and with the differentiation stage in which B-cells were immortalized by EBV infection.