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1.
Drug Deliv Transl Res ; 12(11): 2667-2677, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35015254

RESUMEN

Antibody drugs that target amyloid ß (Aß) are considered possible treatments for Alzheimer's disease; however, most have been dropped from clinical trials. We hypothesized that administration route for antiAß antibody (AntiAß) might affect its therapeutic potential and thus compared delivery of antibodies to the brain and their effect on cognitive dysfunction and amyloid disposition via intravenous (i.v.) and intranasal routes with and without the cell-penetrating peptide, L-penetratin. We demonstrated that intranasal administration with L-penetratin more efficiently delivered human immunoglobulin G (IgG), a model molecule for AntiAß, to the brain compared with i.v. injection. We found that multiple intranasal treatments with Alexa 594-labeled AntiAß (A594-AntiAß) with L-penetratin significantly improved learning by mice with aged amyloid precursor protein (APP) knock-in (App KI mice). Further, intranasal administration of A594-AntiAß increased the amount of soluble Aß (1-42) in the brain, suggesting suppression of Aß aggregation in insoluble form and involvement of activated microglia in Aß clearance. Thus, administration route may be critical for efficient delivery of AntiAß to the brain, and the nose-to-brain delivery with L-penetratin can maximize its therapeutic efficacy.


Asunto(s)
Enfermedad de Alzheimer , Péptidos de Penetración Celular , Anciano , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/farmacología , Precursor de Proteína beta-Amiloide/uso terapéutico , Animales , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Humanos , Inmunoglobulina G/metabolismo , Inyecciones Intravenosas , Ratones
2.
Pharmaceutics ; 13(11)2021 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-34834159

RESUMEN

We previously found that coadministering peptides and proteins with the cell-penetrating peptide L-penetratin intranasally significantly increased transport to the brain and enhanced pharmacological effects. The present study aimed to clarify the mechanisms of nose-to-brain drug delivery enhancement by L-penetratin coadministration. First, we compared the concentrations of Exendin-4 in plasma and brain after intranasal and subcutaneous administration and suggested that coadministration with L-penetratin facilitated the direct nose-to-brain transport of Exendin-4. Second, we demonstrated that L-penetratin did not stimulate the transport of Cy7-labeled Exendin-4 and insulin through the trigeminal nerves but shifted their distribution to the olfactory mucosal pathway. Third, we investigated the distribution of insulin into the deeper regions of the brain after delivery via the olfactory pathway and suggested that insulin had entered the olfactory bulb, bottom part of the brain, and perivascular space through the cerebrospinal fluid and had diffused throughout the brain. We further demonstrated that intranasally delivered insulin with L-penetratin specifically accumulated on the hippocampus neuronal cells. Thus, this study suggested that administrating peptide drugs intranasally with L-penetratin allows direct transport to the olfactory bulb, bottom part of the brain, and perivascular space of the cerebral artery. This technique also potentially allows targeting of specific brain areas.

3.
Mol Reprod Dev ; 84(4): 329-339, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28240438

RESUMEN

Canine induced pluripotent stem cells (ciPSCs) are an attractive source for regenerative veterinary medicine, and may also serve as a disease model for human regenerative medicine. Extending the application of ciPSCs from bench to bedside, however, requires resolving many issues. We generated ciPSCs expressing doxycycline-inducible murine Oct3/4 (Pou5f1), Sox2, Klf4, and c-Myc, which were introduced using lentiviral vectors. The resultant ciPSCs required doxycycline to proliferate in the undifferentiated state. Those ciPSC colonies exhibiting basic fibroblast growth factor (bFGF)-dependent proliferation were dissociated into single cells for passaging, and were maintained on a Matrigel-coated dish without feeder cells in a serum-free medium. The established ciPSCs had the ability to differentiate into three germ layers, via formation of embryoid bodies, as well as into cells expressing the same markers as mesenchymal stem cells. These ciPSCs may thus serve as a suitable source of pluripotent stem cell lines for regenerative veterinary medicine, with fewer concerns of contamination from unknown animal components.


Asunto(s)
Proliferación Celular , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Animales , Perros , Células Nutrientes , Células Madre Pluripotentes Inducidas/citología , Factor 4 Similar a Kruppel , Células Madre Mesenquimatosas/citología , Ratones , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética
4.
Environ Technol ; 36(20): 2603-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25860717

RESUMEN

This study evaluated the performance of unsorted soil media in the slanted soil treatment system, in terms of removal efficiency in suspended solids (SS), chemical oxygen demand (COD), linear alkylbenzene sulphonate (LAS) and Escherichia coli, and lifetime until clogging occurs. Unsorted soil performed longer lifetime until clogging than sorted fine soil. Removal of SS, COD, and LAS also performed same or better level in unsorted soil than fine soil. As reaction coefficients of COD and LAS were described as a function of the hydraulic loading rate, we can design a slanted soil system according to the expected hydraulic loading rate and the targeted level of COD or LAS in effluent. Regarding bacteria removal, unsorted soil performed sufficient reduction of E. coli for 5 weeks; however, the removal process occurred throughout all four chambers, while that of fine soil occurred in one to two chambers.


Asunto(s)
Aguas Residuales/análisis , Aguas Residuales/química , Purificación del Agua/métodos , Ácidos Alcanesulfónicos/química , Escherichia coli , Suelo
5.
Talanta ; 61(2): 203-10, 2003 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-18969179

RESUMEN

A highly sensitive flow-injection method is proposed for the catalytic determination of vanadium(V) at sub-nanogram per milliliter levels using a new indicator reaction. The method is based on the catalytic effect of vanadium(V) on the bromate oxidation of N,N'-bis(2-hydroxyl-3-sulfopropyl)-tolidine. 1,2-Dihydroxybenzene-3,5-disulfonate was used as an activator in the vanadium(V)-catalyzed reaction and significantly enhanced the sensitivity of the method. Vanadium(V) in the range 0.01-3.0 ng ml(-1) was easily determined with sampling rate of about 30 h(-1). Vanadium(IV) could be also determined. The limit of detection (S/N=3) was 0.008 ng ml(-1) and the relative standard deviations were 1.4 and 1.6% for ten determinations of 0.2 ng ml(-1) vanadium(IV) and vanadium(V), respectively. Interferences from metal ions could be suppressed by the addition of ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid) as a masking agent. The proposed method was successfully applied to the determination of vanadium in water samples.

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