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Belov, Vasily

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Belov

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Vasily

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Belov, Vasily
Author's Publications: search.filters.isAuthorOfPublication.b7992695-f611-43fa-a09c-f598e524ac7a

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    Skin Rejuvenation with Non-Invasive Pulsed Electric Fields
    (Nature Publishing Group, 2015) Golberg, Alexander; Khan, S; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael; Georgakoudi, Irene; Papisov, Mikhail; Mihm Jr., Martin C.; Austen Jr., William G.; Yarmush, Martin
    Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.
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    Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, A Calcium Channel Antagonist
    (2016) Rotstein, Benjamin H.; Liang, Huan; Belov, Vasily; Livni, Eli; Levine, Dylan B.; Bonab, Ali A.; Papisov, Mikhail; Perlis, Roy H.; Vasdev, Neil
    In the interest of developing in vivo positron emission tomography (PET) probes for neuroimaging of calcium channels, we have prepared a carbon-11 isotopologue of a dihydropyridine Ca2+-channel antagonist, isradipine. Desmethyl isradipine (4-(benzo[c][1,2,5]oxadiazol-4-yl)-5-(isopropoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine -3-carboxylic acid) was reacted with [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF in an HPLC injector loop to produce the radiotracer in a good yield (6 ± 3% uncorrected radiochemical yield) and high specific activity (143 ± 90 GBq·μmol−1 at end-of-synthesis). PET imaging of normal rats revealed rapid brain uptake at baseline (0.37 ± 0.08 %ID/cc (percent of injected dose per cubic centimeter) at peak, 15–60 s), which was followed by fast washout. After pretreatment with isradipine (2 mg·kg−1, i.p.), whole brain radioactivity uptake was diminished by 25–40%. This preliminary study confirms that [11C]isradipine can be synthesized routinely for research studies and is brain penetrating. Further work on Ca2+-channel radiotracer development is planned.
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    CNS Penetration of Intrathecal-Lumbar Idursulfase in the Monkey, Dog and Mouse: Implications for Neurological Outcomes of Lysosomal Storage Disorder
    (Public Library of Science, 2012) Calias, Pericles; Pan, Jing; Savioli, Nancy; Huang, Yan; Lotterhand, Jason; Alessandrini, Mary; Liu, Nan; Fischman, Alan J.; Powell, Jan L.; Heartlein, Michael W.; Papisov, Mikhail; Belov, Vasily
    A major challenge for the treatment of many central nervous system (CNS) disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome) is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S). I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a) warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b) may have broader implications for CNS treatment with biopharmaceuticals.