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1.
Carbohydr Polym ; 226: 115205, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582062

RESUMO

This study aimed to investigate a standardized biopolymer, cashew gum (CG), in human oesophageal mucosa and mice with experimentally-induced non-erosive reflux disease (NERD). Human oesophageal biopsies from NERD patients were collected to evaluate the mucosal protection of CG through transepithelial electrical resistance (TER), mucosal permeability, and mucoadhesiveness tests. A surgical model of NERD in mice was induced, and barrier functions followed by suggestive oesophageal inflammatory hallmarks were evaluated. Pre-coating of CG was effective in human oesophageal mucosa by attenuating drop of TER and mucosal permeability. Labelled-CG adheres to human oesophageal mucosa for up to 1 h. In animal studies, CG improved parameters of barrier function (TER and mucosal permeability) in distal oesophagus mucosa. CG also promoted sequential support by reducing inflammatory hallmarks of oesophageal damage. CG confers topical oesophageal mucosal protection due to its mucoadhesiveness and anti-inflammatory profile. Long-duration mucoprotective products can be further explored as first-line/adjuvant NERD therapy.


Assuntos
Anacardium/metabolismo , Biopolímeros/farmacologia , Biopolímeros/farmacocinética , Mucosa Esofágica , Refluxo Gastroesofágico/tratamento farmacológico , Adulto , Idoso , Animais , Impedância Elétrica , Mucosa Esofágica/efeitos dos fármacos , Mucosa Esofágica/metabolismo , Feminino , Humanos , Camundongos , Pessoa de Meia-Idade , Permeabilidade/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Adulto Jovem
2.
Appl Microbiol Biotechnol ; 102(3): 1215-1228, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29247366

RESUMO

A strain of embryonic human kidney cells (HEK293) was transiently co-transfected with the expression vectors coding for the α- and ß-subunits of human thyroid-stimulating hormone (hTSH), and, for the first time, a human cell-derived recombinant hTSH was synthesized and extensively characterized. The purification strategy involving two steps provided an overall yield of 55% and a purity level > 90%. The purified material (hTSH-HEK) was analyzed and compared to a CHO-derived recombinant preparation (hTSH-CHO) and to a pituitary-derived (hTSH-Pit) preparation. The three preparations showed an equivalent purity (> 95%) with a hTSH-HEK molecular mass 2.1% lower than that of hTSH-CHO and 2.7% higher than that of hTSH-Pit. Remarkable differences were found in the carbohydrate moiety, the lowest sialic acid content and highest fucose content being observed in hTSH-HEK. In vivo biological activity was confirmed for the three preparations, the hTSH-HEK bioactivity being 39 and 16% lower than those of hTSH-CHO and hTSH-Pit, respectively. The hTSH-HEK circulatory half-life (t 1/2) was also shorter than those of hTSH-CHO (1.5-fold) and hTSH-Pit (1.2-fold). According to these findings, HEK-293-derived hTSH can be considered to be useful for clinical applications, in view as well of its human origin and particular carbohydrate composition.


Assuntos
Carboidratos/análise , Células Epiteliais/metabolismo , Glicoproteínas/biossíntese , Tireotropina/biossíntese , Animais , Células CHO , Cricetinae , Cricetulus , Fucose/análise , Glicosilação , Células HEK293 , Meia-Vida , Humanos , Ácido N-Acetilneuramínico/análise , Proteínas Recombinantes/biossíntese , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Transfecção
3.
Laryngoscope ; 128(5): 1157-1162, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29076531

RESUMO

OBJECTIVES/HYPOTHESIS: Evaluate the effect of in vitro exposure of mice laryngeal mucosa to solutions that simulated human gastric juice and to assess the topical protective effect of cashew gum on mice laryngeal mucosal integrity in vitro. STUDY DESIGN: Animal study. METHODS: Murine (Swiss) laryngeal samples were mounted in Ussing chambers. The luminal side of biopsies was exposed to solutions of different acidity with or without pepsin and/or taurodeoxycholic acid (TDC). Transepithelial electrical resistance (TER) was continuously recorded. The topical protective effect of cashew gum solution was evaluated by precoating the biopsies before the exposure with a solution at pH 5 containing 5 mM TDC. Changes in TER and mucosal permeability to fluorescein were measured. RESULTS: Exposure of laryngeal mucosa to acidic solutions containing pepsin and TDC provoked a pH-dependent drop in TER with the maximal effect at pH 1, but still present at pH 5 (weakly acidic). The exposure of the laryngeal mucosa to a solution of pH 5 with TDC, but not with pepsin, produced a dose-dependent decrease in TER. Precoating the mucosa with cashew gum prevented the reduction of TER and increased transepithelial permeability by exposure to a solution at pH5 containing TDC. CONCLUSIONS: Weakly acidic solutions containing bile acids can produce impairment of laryngeal epithelial barrier, which may be protected by topical treatment with cashew gum. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1157-1162, 2018.


Assuntos
Anacardium , Mucosa Laríngea/efeitos dos fármacos , Extratos Vegetais/farmacologia , Administração Tópica , Animais , Masculino , Camundongos , Pepsina A/farmacologia , Extratos Vegetais/administração & dosagem , Ácido Taurodesoxicólico/farmacologia
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