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101.
Improved retention of idarubicin after intravenous injection obtained for cholesterol-free liposomes
Dos Santos N Mayer LD Abraham SA Gallagher RC Cox KA Tardi PG Bally MB 《Biochimica et biophysica acta》2002,1561(2):188-201
To date there has been a focus on the application of sterically stabilized liposomes, composed of saturated diacylphospholipid, polyethylene glycol (PEG) conjugated lipids (5-10 mole%) and cholesterol (CH) (>30 mole%), for the systemic delivery of drugs. However, we are now exploring the utility of liposome formulations composed of diacylphospholipid conjugated PEG mixtures prepared in the absence of added cholesterol, with the primary objective of developing formulations that retain encapsulated drug better than comparable formulations prepared with cholesterol. In this report the stability of cholesterol-free distearoylphosphatidylcholine (DSPC):distearoylphosphatidylethanolamine (DSPE)-PEG(2000) (95:5 mol/mol) liposomes was characterized in comparison to cholesterol-containing formulations DSPC:CH (55:45 mol/mol) and DSPC:CH:DSPE-PEG(2000) (50:45:5 mol/mol/mol), in vivo. Circulation longevity of these formulations was determined in consideration of variables that included varying phospholipid acyl chain length, PEG content and molecular weight. The application of cholesterol-free liposomes as carriers for the hydrophobic anthracycline antibiotic, idarubicin (IDA), was assessed. IDA was encapsulated using a transmembrane pH gradient driven process. To determine stability in vivo, pharmacokinetic studies were performed using 'empty' and drug-loaded [(3)H]cholesteryl hexadecyl ether radiolabeled liposomes administered intravenously to Balb/c mice. Inclusion of 5 mole% of DSPE-PEG(2000) or 45 mole% cholesterol to DSPC liposomes increased the mean plasma area under the curve (AUC(0-24h)) 19-fold and 10-fold, respectively. Cryo-transmission electron micrographs of IDA loaded liposomes indicated that the drug formed a precipitate within liposomes. The mean AUC(0-4h) for free IDA was 0.030 micromole h/ml as compared to 1.38 micromole h/ml determined for the DSPC:DSPE-PEG(2000) formulation, a 45-fold increase, demonstrating that IDA was retained better in cholesterol-free compared to cholesterol-containing liposomes. 相似文献
102.
Expression of Bcl-2 in Adult Human Brain Regions with Special Reference to Neurodegenerative Disorders 总被引:5,自引:0,他引:5
Sheela Vyas France Javoy-Agid María-Trinidad Herrero Ornella Strada Florence Boissiere †Urzula Hibner Yves Agid 《Journal of neurochemistry》1997,69(1):223-231
Abstract: The expression of the protooncogene bcl-2 , an inhibitor of apoptosis in various cells, was examined in the adult human brain. Several experimental criteria were used to verify its presence; mRNA was analyzed by northern blot with parallel experiments in mouse tissues, by RNase protection, and by in situ hybridization histochemistry. Bcl-2 protein was detected by western blot analysis and immunohistochemistry. Two bcl-2 mRNA species were identified in the human brain. The pattern of distribution of bcl-2 mRNA at the cellular level showed labeling in neurons but not glia. The in situ hybridization signal was stronger in the pyramidal neurons of the cerebral cortex and in the cholinergic neurons of the nucleus basalis of Meynert than in the Purkinje neurons of the cerebellum. Both melanized and nonmelanized neurons were labeled in the substantia nigra. In the striatum, bcl-2 mRNA was detected in some but not all neurons. In the regions examined for Bcl-2 protein, the expression pattern correlated with the mRNA results. In patients with Alzheimer's and Parkinson's diseases, quantification of bcl-2 mRNA in the nucleus basalis of Meynert and substantia nigra, respectively, showed that the expression was unaltered compared with controls, raising the possibility that the expression of other components of apoptosis is modulated. 相似文献
103.
Xi-Lin Chen Daniel Serrano Farnaz Ghobadi Marian Mayhue Kasper Hoebe Subburaj Ilangumaran Sheela Ramanathan 《PloS one》2016,11(3)
GTPase of the immune associated nucleotide binding protein (GIMAP) family of proteins are expressed essentially in cells of the hematopoietic system. Mutation in the founding member of this gene family, Gimap5, results in the lymphopenic phenotype in Bio-Breeding diabetes prone rats. In mice, deletion of functional Gimap5 gene affects the survival and renewal of hematopoietic stem cells in addition to the defects observed in T cells. Here we show that T cells from OTII TCR-transgenic Gimap5sph/sph mice do not proliferate in response to its cognate antigen. Furthermore, T cells from Gimap5 mutant rats and mice show decreased phosphorylation of STAT5 following stimulation with IL-7. Our results suggest that functional Gimap5 is required for optimal signaling through TCR and IL-7R in T cells. 相似文献
104.
Salvinia showed capacity to accumulate and hence remove more than one heavy metal from multi-metal solutions, though efficiency for heavy metal uptake varied for each metal present in different combinations. The pattern of heavy metal accumulation was confirmed by energy-dispersive X-ray fluorescence (EDXRF) analysis. There was a gradual decrease in heavy metal content in the wastewater samples when fresh biomass was replenished at definite time intervals of treatment. Zn, Cu, Ni and Cr removal to the extent of 84.8%, 73.8%, 56.8%, and 41.4%, respectively, was noted after four samplings of fresh biomass replenishment. Salvinia therefore can be recommended as a species for cleaning water contaminated with heavy metals. 相似文献
105.
106.
Veena Menon Elizabeth Gold Ramona Godbole Delivette Castor Hally Mahler Steven Forsythe Mariam Ally Emmanuel Njeuhmeli 《PloS one》2014,9(5)
Background
Given the proven effectiveness of voluntary medical male circumcision (VMMC) in preventing the spread of HIV, Tanzania is scaling up VMMC as an HIV prevention strategy. This study will inform policymakers about the potential costs and benefits of scaling up VMMC services in Tanzania.Methodology
The analysis first assessed the unit costs of delivering VMMC at the facility level in three regions—Iringa, Kagera, and Mbeya—via three currently used VMMC service delivery models (routine, campaign, and mobile/island outreach). Subsequently, using these unit cost data estimates, the study used the Decision Makers'' Program Planning Tool (DMPPT) to estimate the costs and impact of a scaled-up VMMC program.Results
Increasing VMMC could substantially reduce HIV infection. Scaling up adult VMMC to reach 87.9% coverage by 2015 would avert nearly 23,000 new adult HIV infections through 2015 and an additional 167,500 from 2016 through 2025—at an additional cost of US$253.7 million through 2015 and US$302.3 million from 2016 through 2025. Average cost per HIV infection averted would be US$11,300 during 2010–2015 and US$3,200 during 2010–2025. Scaling up VMMC in Tanzania will yield significant net benefits (benefits of treatment costs averted minus the cost of performing circumcisions) in the long run—around US$4,200 in net benefits for each infection averted.Conclusion
VMMC could have an immediate impact on HIV transmission, but the full impact on prevalence and deaths will only be apparent in the longer term because VMMC averts infections some years into the future among people who have been circumcised. Given the health and economic benefits of investing in VMMC, the scale-up of services should continue to be a central component of the national HIV prevention strategy in Tanzania. 相似文献107.
B. Aneeba S.V. Ashvin Santhia R. Sheela Christy Fahad A. Al-Misned Hamed A. El-Serehy S. Vinu 《Saudi Journal of Biological Sciences》2021,28(1):395-399
The incorporation of succinic acid (SA) in the lattice of L-Lysine monohydrochloride (LM) has opened the new avenue in the field of production and application of scintillator materials such as LED and antifungal drug. Crystalline trait and monoclinic structure were scanned by XRD. The existence of carbonyl, carboxylate and protonated amine group were confirmed through FTIR and UV spectra predicted the transmittance of SA: LM crystal. Polychromatic luminescence behaviour had achieved through the incorporation of SA instead of blue luminescence, which is a new result. Also SA: LM exhibited good response towards pathogenic fungi which causes numerous types of infections and diseases in both humans and animals. The high inhibitory zone at 16 mm was formed by the grown SA: LM crystal against the life threatening fungi like Candida albicans. Also fungal inhibition against candida parapsilosis and Aspergillus flaves, respectively, were tuned by the inclusion of succinic acid. 相似文献
108.
Arturo Loaiza-Bonilla Daniel Horowitz Sheenu Sheela Anupa Baral Gabriel Tinoco Christos Kyriakopoulos 《Journal of medical case reports》2011,5(1):1-6
Introduction
Crohn's disease is a chronic inflammatory bowel disease of unknown etiology which may affect any part of the bowel. Fistulas are a common and often serious complication of Crohn's disease. The treatment for fistulizing Crohn's disease can be medical, surgical or a combination of the two. Recently, adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, has been suggested as a safe and effective treatment for the induction and maintenance of remission in adult patients with moderate to severe Crohn's disease, who are refractory to conventional therapy or intolerant to infliximab. However, large studies focusing on evaluating the efficacy of adalimumab in fistulizing Crohn's disease have not yet been published.Case presentation
We report the cases of three patients, of European Caucasian ethnicity and Greek nationality, with active luminal and fistulizing Crohn's disease. All of the cases were treated successfully with adalimumab. Patient 1 (a 44-year-old man) and patient 2 (an 18-year-old woman) developed early post-surgical enterocutaneous fistulas, while patient 3 (a 20-year-old woman) had peri-anal fistulizing Crohn's disease. Adalimumab treatment (160 mg subcutaneously at week zero, 80 mg at week two, and 40 mg every other week) was used for three different indications: (1) after the failure of other conservative medical treatments for Crohn's disease (patient 1); (2) as a monotherapy in treating a naive patient (patient 2); (3) after an intolerance to infliximab (patient 3). A remission of the active luminal and fistulizing disease was achieved soon after the initiation of adalimumab and sustained thereafter with maintenance doses. No further surgical intervention was required and no adverse effects were observed in any of the cases.Conclusions
Fistulizing Crohn's disease remains a challenge in clinical practice. Adalimumab seems to be an effective, well-tolerated and safe treatment option for the induction and maintenance of remission in patients with moderate to severe peri-anal fistulizing Crohn's disease. Furthermore, adalimumab seems to be a promising treatment option for patients with moderate to severe fistulizing Crohn's disease with enterocutaneous fistulas. However, this clinical observation needs to be investigated in further clinical trials. 相似文献109.
Harris DM Hazan-Haley I Coombes K Bueso-Ramos C Liu J Liu Z Li P Ravoori M Abruzzo L Han L Singh S Sun M Kundra V Kurzrock R Estrov Z 《PloS one》2011,6(6):e21250
Patients with prolonged myelosuppression require frequent platelet and occasional granulocyte transfusions. Multi-donor transfusions induce alloimmunization, thereby increasing morbidity and mortality. Therefore, an autologous or HLA-matched allogeneic source of platelets and granulocytes is needed. To determine whether nonhematopoietic cells can be reprogrammed into hematopoietic cells, human mesenchymal stromal cells (MSCs) and skin fibroblasts were incubated with the demethylating agent 5-azacytidine (Aza) and the growth factors (GF) granulocyte-macrophage colony-stimulating factor and stem cell factor. This treatment transformed MSCs to round, non-adherent cells expressing T-, B-, myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and mRNA array analysis suggested that Aza and GF treatment demethylated and activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further studies are needed to determine whether transformed MSCs or skin fibroblasts are suitable for therapy. 相似文献
110.
Levecke B Behnke JM Ajjampur SS Albonico M Ame SM Charlier J Geiger SM Hoa NT Kamwa Ngassam RI Kotze AC McCarthy JS Montresor A Periago MV Roy S Tchuem Tchuenté LA Thach DT Vercruysse J 《PLoS neglected tropical diseases》2011,5(6):e1201