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Being able to carry zidovudine (AZT) at known concentrations into CD4+/CD38+ and CD14+ cells permits:
Further studies are necessary in order to:
相似文献
| - to reduce the drug dosage and to increase the interval for administration (until 1 dose I.V. every week); |
| - to modulate the drug concentration into the CD4+/CD38 an CD14+ cells in relation to the in vitro determined HIV sensitiveness; |
| - to eliminate haematological, medullary and general toxicity; |
| - to be able to treat severely hill patients. |
| - To find out the better phase to start the therapy; |
| - To use several drugs with different mechanisms of action in order to slow down as much as possible the presence of resistant viral strains. |
| - As for other drugs which are beginning to be used with artificial vehicles, futher studies are required to improve the selectivity and safety of LIPOAZT for the target cells including macrophages. |
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Summary Membranes of liver peroxisomes from rats fed with clofibrate were purified in a discontinuous gradient using a zonal rotor. The preparation consists of round or oval vesicles mostly devoid of nucleoids with a diameter ranging from 70–700 nm; open sheets are found very infrequently. Mitochondrial profiles as well as vesicles containing cytochemically demonstrable glucose 6-phosphatase are scarce; accordingly, glucose 6-phosphatase is nearly undetectable biochemically. Monoamine oxidase is absent in peroxisomal membranes. Cytochrome b5 is found in a concentration of 0.3 nmoles/mg protein, an order of magnitude comparable to the content of endoplasmic reticulum membranes. Reduction of this cytochrome with palmitoyl-CoA is possible only after recombination of the membranes with the soluble peroxisomal matrix fraction. 相似文献
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Di Paola R Caporarello N Marucci A Dimatteo C Iadicicco C Del Guerra S Prudente S Sudano D Miele C Parrino C Piro S Beguinot F Marchetti P Trischitta V Frittitta L 《PloS one》2011,6(5):e19462
The aim of this study was to deeper investigate the mechanisms through which ENPP1, a negative modulator of insulin receptor (IR) activation, plays a role on insulin signaling, insulin secretion and eventually glucose metabolism. ENPP1 cDNA (carrying either K121 or Q121 variant) was transfected in HepG2 liver-, L6 skeletal muscle- and INS1E beta-cells. Insulin-induced IR-autophosphorylation (HepG2, L6, INS1E), Akt-Ser(473), ERK1/2-Thr(202)/Tyr(204) and GSK3-beta Ser(9) phosphorylation (HepG2, L6), PEPCK mRNA levels (HepG2) and 2-deoxy-D-glucose uptake (L6) was studied. GLUT 4 mRNA (L6), insulin secretion and caspase-3 activation (INS1E) were also investigated. Insulin-induced IR-autophosphorylation was decreased in HepG2-K, L6-K, INS1E-K (20%, 52% and 11% reduction vs. untransfected cells) and twice as much in HepG2-Q, L6-Q, INS1E-Q (44%, 92% and 30%). Similar data were obtained with Akt-Ser(473), ERK1/2-Thr(202)/Tyr(204) and GSK3-beta Ser(9) in HepG2 and L6. Insulin-induced reduction of PEPCK mRNA was progressively lower in untransfected, HepG2-K and HepG2-Q cells (65%, 54%, 23%). Insulin-induced glucose uptake in untransfected L6 (60% increase over basal), was totally abolished in L6-K and L6-Q cells. GLUT 4 mRNA was slightly reduced in L6-K and twice as much in L6-Q (13% and 25% reduction vs. untransfected cells). Glucose-induced insulin secretion was 60% reduced in INS1E-K and almost abolished in INS1E-Q. Serum deficiency activated caspase-3 by two, three and four folds in untransfected INS1E, INS1E-K and INS1E-Q. Glyburide-induced insulin secretion was reduced by 50% in isolated human islets from homozygous QQ donors as compared to those from KK and KQ individuals. Our data clearly indicate that ENPP1, especially when the Q121 variant is operating, affects insulin signaling and glucose metabolism in skeletal muscle- and liver-cells and both function and survival of insulin secreting beta-cells, thus representing a strong pathogenic factor predisposing to insulin resistance, defective insulin secretion and glucose metabolism abnormalities. 相似文献
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Peluso M Munnia A Piro S Jedpiyawongse A Sangrajrang S Giese RW Ceppi M Boffetta P Srivatanakul P 《Free radical research》2012,46(1):85-92
Diet has been shown to modulate M(1)dG adduct, a biomarker of oxidative stress and lipid peroxidation. Thus, we analysed the association between diet and M(1)dG in 120 controls and 67 Map Ta Phut industrial estate workers in Rayong, Thailand, to evaluate the influence of fruit and vegetables, and fried and charcoal-grilled/barbecued food consumption on M(1)dG. M(1)dG was decreased in controls reporting to consume 14-17 servings/week of fruit and vegetables (mean ratio [MR]= 0.35, CI 0.18-0.69, p< 0.05). Conversely, a non-statistically significant M(1)dG increment was detected in controls consuming 9-18 servings/week of fried food (MR = 1.33, CI 0.88-2.00, p = 0.168). No effect of charcoal-grilled/barbecued food was found. No effect of diet was observed in workers. An association with smoking was observed in controls (MR = 1.88, CI 1.14-3.10, p < 0.05), but not in workers. M(1)dG can induce mutations and/or methylation changes within the promoter regions of cancer-related genes, thus promotion of healthy eating practices should be recommended. 相似文献
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Mori F Piro FR Della Rocca C Mesiti G Giampaoli S Silvestre G Lazzaro D 《Histology and histopathology》2007,22(1):61-77
In the evolution of colon rectal cancer (CRC) the imbalance between cell proliferation and apoptosis is considered one of the prominent causes of tumor induction and/or progression. In order to establish the role of anti apoptotic proteins in colon cancer development, we studied with immunohistochemical techniques the expression of Survivin in a mouse model of colon carcinogenesis induced by 1,2-dimethyl-hydrazine treatment. In this mouse model Survivin was over-expressed during tumor development, showing a distribution mimicking that described in the correspondent human malignancies. We also correlated Survivin distribution with COX-2 and beta-Catenin expression patterns. The co-localization of COX-2/beta-Catenin/Survivin in the same epithelial cells in tumor samples lends credence to possible in vivo regulatory effects of COX-2 and beta-Catenin on the intracellular Survivin levels in mouse and human colon cancer. 相似文献
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Tagarelli G Fiorini S Piro A Luiselli D Tagarelli A Pettener D 《Collegium antropologicum》2007,31(1):331-338
Cultural and environmental factors interact in determining the genetic structure of human populations. Bio-demographic investigations of ethnic minorities are able to disentangle the influences that these two components have on the evolution of the genetic structure of a population. The ethnic minority of the Arb?reshe of the province of Cosenza (Calabria, southern Italy) is analyzed in this paper and its bio-demographic structure in the early 1800s is compared with that of neighboring Italian populations. The data derive from surnames recorded in the birth registers of the 19 Arbdreshe municipalities of the province of Cosenza and in 5 non-Arb?reshe municipalities of the same province. Isonymy and repeated pairs of surnames are used to analyze the bio-demographic structure of these populations, while analysis of isonymic relationships is used to investigate the variability between populations. Higher values of marital isonymy and subdivision into subpopulations characterize the Arb?reshe populations with respect to their non-Arb?reshe neighbors. However, the high range of variability of these parameters suggests a strong influence of geographic location on the marriage pattern of each community. At the same time, cultural differences linked to group identity had a strong impact in limiting marriage exchanges between the different ethnic groups living in the province of Cosenza in the early 1800s. In fact, the analysis of isonymic relationships demonstrates that geographic location shaped kinship patterns among the Arbereshe communities, but it also shows that the non-Arb?reshe neighbors formed a clearly separate reproductive cluster. 相似文献
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