内皮腫

English Journal

Controlling ferrofluid permeability across the blood-brain barrier model.

Shi D1, Sun L, Mi G, Sheikh L, Bhattacharya S, Nayar S, Webster TJ.Author information 1Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.AbstractIn the present study, an in vitro blood-brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood-brain barrier model was completed by examining the permeability of FITC-Dextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood-brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood-brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood-brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood-brain barrier (e.g. CPB).
Nanotechnology.Nanotechnology.2014 Jan 23;25(7):075101. [Epub ahead of print]
In the present study, an in vitro blood-brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood-brain barrier model was completed by examining the permeability of FITC-Dextran at increasing exposure times up to 96 h in serum-free medium and
PMID 24457539

A Myristoylated Cell-Penetrating Peptide Bearing a Transferrin Receptor-Targeting Sequence for Neuro-Targeted siRNA Delivery.

Youn P1, Chen Y, Furgeson DY.Author information 1Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah , Salt Lake City, Utah 84112, United States.AbstractMany neurodegenerative disorders (NDDs) are characterized by aggregation of aberrant proteins and extensive oxidative stress in brain cells. As a treatment option for NDDs, RNA interference (RNAi) is a promising approach to suppress the activation of abnormal genes and negative regulators of antioxidant genes. Efficient neuro-targeted siRNA delivery requires a delicate optimization of nucleic acid carriers, quite distinct from putative pDNA carriers in regard to stable condensation and serum protection of siRNA, blood-brain barrier (BBB) bypass, effective siRNA delivery to brain cells, and functional release of bioactive siRNA at therapeutic levels. Here, we propose that a myristic acid conjugated, cell-penetrating peptide (transportan; TP), equipped with a transferrin receptor-targeting peptide (myr-TP-Tf), will lead to stable encapsulation of siRNA and targeted delivery of siRNA to brain cells overcoming the BBB. Myr-TP-Tf was successfully prepared by solid-phase peptide synthesis with high purity. Myr-TP-Tf-siRNA complexes formulated at a 20:1 (peptide-siRNA) molar ratio provided prolonged siRNA stability against serum and ribonuclease treatment. Fluorescence images clearly indicated that siRNA uptake was successfully achieved by myr-TP-Tf complexes in both a murine brain endothelioma and a human glioma cell line. The luciferase assay and the human placental alkaline phosphatase (hPAP) reporter assay results demonstrated the functional gene silencing effect of myr-TP-Tf-siRNA complexes in a human glioma cell line as well as in primary murine neurons/astrocytes, supportive of successful release of bioactive siRNA into the cytosol. Finally, the transcytosis assay revealed that favorable siRNA transport via receptor-mediated transcytosis was mediated by myr-TP-Tf complexes. In summary, these data suggest that myr-TP-Tf peptides possess promising properties as a vehicle for neuro-targeted siRNA delivery. We will further study this peptide in vitro and in vivo for transport mechanism kinetics and to validate its capability to deliver siRNA to the brain, respectively.
Molecular pharmaceutics.Mol Pharm.2014 Jan 16. [Epub ahead of print]
Many neurodegenerative disorders (NDDs) are characterized by aggregation of aberrant proteins and extensive oxidative stress in brain cells. As a treatment option for NDDs, RNA interference (RNAi) is a promising approach to suppress the activation of abnormal genes and negative regulators of antioxi
PMID 24387132

Human endothelial dihydrofolate reductase low activity limits vascular tetrahydrobiopterin recycling.

Whitsett J1, Rangel Filho A, Sethumadhavan S, Celinska J, Widlansky M, Vasquez-Vivar J.Author information 1Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.AbstractTetrahydrobiopterin (BH₄) is required for NO synthesis and inhibition of superoxide release from endothelial NO synthase. Clinical trials using BH₄ to treat endothelial dysfunction have produced mixed results. Poor outcomes may be explained by the rapid systemic and cellular oxidation of BH₄. One of the oxidation products of BH₄, 7,8-dihydrobiopterin (7,8-BH₂), is recycled back to BH₄ by dihydrofolate reductase (DHFR). This enzyme is ubiquitously distributed and shows a wide range of activity depending on species-specific factors and cell type. Information about the kinetics and efficiency of BH4 recycling in human endothelial cells receiving BH₄ treatment is lacking. To characterize this reaction, we applied a novel multielectrode coulometric HPLC method that enabled the direct quantification of 7,8-BH₂ and BH₄, which is not possible with fluorescence-based methodologies. We found that basal untreated BH₄ and 7,8-BH₂ concentrations in human endothelial cells (ECs) are lower than in bovine and murine endothelioma cells. Treatment of human ECs with BH₄ transiently increased intracellular BH₄ while accumulating the more stable 7,8-BH₂. This was different from bovine or murine ECs, which resulted in preferential BH₄ increase. Using BH₄ diastereomers, 6S-BH₄ and 6R-BH₄, the narrow contribution of enzymatic DHFR recycling to total intracellular BH₄ was demonstrated. Reduction of 7,8-BH₂ to BH₄ occurs at very slow rates in cells and needs supraphysiological levels of 7,8-BH₂, indicating this reaction is kinetically limited. Activity assays verified that human DHFR has very low affinity for 7,8-BH₂ (DHF<Km>7,8-BH₂) and folic acid inhibits 7,8-BH₂ recycling. We conclude that low activity of endothelial DHFR is an important factor limiting the benefits of BH4 therapies, which may be further aggravated by folate supplements.
Free radical biology & medicine.Free Radic Biol Med.2013 Oct;63:143-50. doi: 10.1016/j.freeradbiomed.2013.04.035. Epub 2013 May 23.
Tetrahydrobiopterin (BH₄) is required for NO synthesis and inhibition of superoxide release from endothelial NO synthase. Clinical trials using BH₄ to treat endothelial dysfunction have produced mixed results. Poor outcomes may be explained by the rapid systemic and cellular oxidation of BH₄.
PMID 23707606

Japanese Journal

海綿状血管腫，限局性結節性過形成が合併した肝類上皮性血管内皮腫の1切除例

水上達三,神山俊哉,中西一彰,横尾英樹,田原宗徳,福森大介,蒲池浩文,松下通明,藤堂省
日本消化器外科学会雑誌 44(2), 131-137, 2011
　症例は44歳の女性で，生来著患はないが，経口避妊薬の内服歴があった．2008年10月，健診にて肝機能異常を指摘され，腹部エコーを施行したところ，肝両葉に最大径が38mmで低～高エコーの多発する腫瘍を指摘された．CTでは肝両葉の辺縁を中心に，多発性の腫瘤性病変を認めるも確定診断に至らなかった．腹腔鏡下肝生検を施行し，肝類上皮性血管内皮腫（以下，H-EHEと略記）の診断となり移植を含めた加療目的に当 …
NAID 130004907997

切歯乳頭部に生じた類上皮血管内皮腫の1例

今敬生,佐藤寿,榊宏剛,中川祥,小林恒,木村博人
日本口腔外科学会雑誌 57(4), 217-220, 2011
… Immunohistochemical staining of the excisional biopsy specimen showed tumor cells positive for Factor VIII related antigen, CD31, and CD34, which are vascular endothelioma markers. …
NAID 130004567608