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1.
Int J Nanomedicine ; 14: 6297-6311, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496687

RESUMO

Purpose: Mn-doped ZnS quantum dots (QDs) with special luminescent properties have been widely researched and applied in various fields. Thus, their release toxicity and security cannot be ignored. Methods: In the present study, the toxicity and non-targeted metabolomics of Mn-doped ZnS QDs were investigated after single intravenous injection. Serum metabolites were evaluated based on gas chromatography-mass spectrometry together with multivariate statistical analyses [principal component analysis, partial least squares discriminant analysis, and orthogonal PLS-DA]. Results: The modified metabolites (variable importance in the projection (VIP) >1 and p<0.05) revealed that Mn-doped ZnS QDs exposure disturbed glycolysis, tricarboxylic acid cycle, ketoplasia, glutaminolysis, and amino acid and lipid metabolism. The behavior, coefficients of organs, and histological changes were the same as in the control group, and the disturbance of hematology and serum biochemistry was not dose- or time-dependent. Conclusion: Our study provides a general observation regarding the toxicity and potential metabolic responses of mice exposed to Mn-doped ZnS QDs.


Assuntos
Manganês/química , Metabolômica , Pontos Quânticos/toxicidade , Sulfetos/sangue , Sulfetos/toxicidade , Compostos de Zinco/sangue , Compostos de Zinco/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Metaboloma , Camundongos Endogâmicos BALB C , Análise Multivariada , Tamanho do Órgão/efeitos dos fármacos , Pontos Quânticos/administração & dosagem , Pontos Quânticos/química , Sulfetos/administração & dosagem , Compostos de Zinco/administração & dosagem
2.
Optom Vis Sci ; 96(9): 647-654, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31479019

RESUMO

SIGNIFICANCE: This present study advances our knowledge on the role of lifestyle factors in myopia (short-sightedness), specifically dietary factors. It has been suggested in previous studies that lower zinc status is associated with myopia; however, this article shows no relationship between dietary zinc intake and myopia in U.S. adolescents. PURPOSE: It has been suggested that low zinc levels may contribute to the development of myopia. The aim of the present study is to examine, for the first time in a Western population, the association of total dietary and supplement zinc intake with myopia. METHODS: A total of 1095 children/adolescents aged 12 to 19 years who participated in the U.S. National Health and Nutrition Examination Survey from 2007 to 2008 were enrolled in this study. Multivariate logistic regression analysis was performed to examine the relationship between total zinc intake and myopia after adjustment for potential confounders. In addition, the association between total zinc intake and spherical equivalent refractive error was examined in the myopia group through multiple linear regression. RESULTS: Among study participants, 30% were found to be myopic (≤-1.00 D). Although median total daily zinc intake was lower among myopes (10.8 [10.2] mg/d) than among nonmyopes (11.1 [10.8] mg/d), the difference was not statistically significant (P = .11). In multiple logistic regression analyses, zinc and copper intakes were not significantly associated with myopia after adjustment for age, sex, body mass index, ethnicity, family income, recreational activity, copper intake, and daily energy intake (in kilocalories per day). In multiple linear regression, spherical equivalent refractive error was not associated with total zinc intake in the myopic group after adjustment for confounding factors (P = .13). CONCLUSIONS: In contrast to previous Asian studies, total zinc intake is not associated with the presence of myopia in U.S. adolescents/children.


Assuntos
Dieta , Miopia/epidemiologia , Compostos de Zinco/administração & dosagem , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Estados Unidos/epidemiologia , Adulto Jovem
3.
Int J Mol Sci ; 20(11)2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185643

RESUMO

Maslinic acid is a pentacyclic triterpene with a plethora of biological activities, including anti-inflammatory, antioxidant, antimicrobial, cardioprotective, and antitumor effects. New derivatives with improved properties and broad-spectrum activity can be obtained following structural changes of the compound. The present study was aimed to characterize a benzylamide derivative of maslinic acid-benzyl (2α, 3ß) 2,3-diacetoxy-olean-12-en-28-amide (EM2)-with respect to the anti-angiogenic and anti-inflammatory effects in two in vivo experimental models. Consequently, the compound showed good tolerability and lack of irritation in the chorioallantoic membrane assay with no impairment of the normal angiogenic process during the tested stages of development. In the acute ear inflammation murine model, application of EM2 induced a mild anti-inflammatory effect that was potentiated by the association with zinc chloride (ZnCl2). A decrease in dermal thickness of mice ears was observed when EM2 and ZnCl2 were applied separately or in combination. Moreover, hyalinization of the dermis appeared only when EM2 was associated with ZnCl2, strongly suggesting the role of their combination in wound healing.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Otite/tratamento farmacológico , Triterpenos/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Embrião de Galinha , Cloretos/administração & dosagem , Cloretos/uso terapêutico , Membrana Corioalantoide/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Camundongos , Triterpenos/administração & dosagem , Triterpenos/efeitos adversos , Compostos de Zinco/administração & dosagem , Compostos de Zinco/uso terapêutico
4.
Int J Pharm ; 566: 541-548, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31173801

RESUMO

The effect of mild hyperthermia (MHT) on nanoparticle (NP) accumulation in rat model liver metastasis and the contribution of neoplastic and non-neoplastic cells were characterized. CdSe/ZnS QD-doped poly(lactic-co-glycolic acid) (PLGA) NPs (155 ±â€¯10 nm) were delivered via the ileocolic vein to metastatic livers 15 min after localized MW irradiation (1 min, 41 °C) or in normothermia (37 °C, NT). Quantitative analysis of tissue sections by confocal fluorescence microscopy 1 h after NP injection showed no NP tumor accumulation in NT. On the contrary, MHT increased NP association with tumor, compared to normal tissue. Counterstaining of specific markers showed that the MHT effect is due to an increased NP endocytosis not only by tumor cells, but also by hepatocytes at the growing tumor edge and, to a minor extent, by tumor-associated macrophages. High-NP capturing hepatocytes, close to the tumor, may be a relevant phenomenon in MHT-induced increased targeting of NPs to liver metastasis, influencing their therapeutic efficacy.


Assuntos
Portadores de Fármacos/administração & dosagem , Hepatócitos/metabolismo , Hipertermia Induzida , Neoplasias Hepáticas/metabolismo , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Animais , Compostos de Cádmio/administração & dosagem , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Macrófagos do Fígado/metabolismo , Neoplasias Hepáticas/secundário , Macrófagos/metabolismo , Masculino , Ratos , Compostos de Selênio/administração & dosagem , Sulfetos/administração & dosagem , Compostos de Zinco/administração & dosagem
5.
Respir Res ; 20(1): 36, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770755

RESUMO

BACKGROUND: Lung injury due to zinc chloride smoke inhalation is very common in military personnel and leads to a high incidence of pulmonary complications and mortality. The aim of this study was to uncover the underlying mechanisms of lung injury due to zinc chloride smoke inhalation using a rat model. METHODS: Histopathology analysis of rat lungs after zinc chloride smoke inhalation was performed by using haematoxylin and eosin (H&E) and Mallory staining. A lung injury rat model of zinc chloride smoke inhalation (smoke inhalation for 1, 2, 7 and 14 days) was developed. First, isobaric tags for relative and absolute quantization (iTRAQ) and weighted gene co-expression network analysis (WGCNA) were used to identify important differentially expressed proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to study the biological functions of differentially expressed proteins. Then, analysis of lung injury repair-related differentially expressed proteins in the early (day 1 and day 2) and middle-late stages (day 7 and day 14) of lung injury after smoke inhalation was performed, followed by the protein-protein interaction (PPI) analysis of these differentially expressed proteins. Finally, the injury repair-related proteins PARK7 and FABP5 were validated by immunohistochemistry and western blot analysis. RESULTS: Morphological changes were observed in the lung tissues after zinc chloride smoke inhalation. A total of 27 common differentially expressed proteins were obtained on days 1, 2, 7 and 14 after smoke inhalation. WGCNA showed that the turquoise module (which involved 909 proteins) was most associated with smoke inhalation time. Myl3, Ckm, Adrm1 and Igfbp7 were identified in the early stages of lung injury repair. Gapdh, Acly, Tnni2, Acta1, Actn3, Pygm, Eno3 and Tpi1 (hub proteins in the PPI network) were identified in the middle-late stages of lung injury repair. Eno3 and Tpi1 were both involved in the glycolysis/gluconeogenesis signalling pathway. The expression of PARK7 and FABP5 was validated and was consistent with the proteomics analysis. CONCLUSION: The identified hub proteins and their related signalling pathways may play crucial roles in lung injury repair due to zinc chloride smoke inhalation.


Assuntos
Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/patologia , Cloretos/toxicidade , Proteômica/métodos , Lesão por Inalação de Fumaça/genética , Lesão por Inalação de Fumaça/patologia , Compostos de Zinco/toxicidade , Lesão Pulmonar Aguda/induzido quimicamente , Administração por Inalação , Animais , Cloretos/administração & dosagem , Expressão Gênica , Masculino , Ratos , Ratos Wistar , Lesão por Inalação de Fumaça/induzido quimicamente , Compostos de Zinco/administração & dosagem
6.
Food Chem Toxicol ; 125: 439-451, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30711718

RESUMO

This study aimed to evaluate the hepatoprotective effect of whey protein nanoparticles (WP-NPs) coated Zinc citrate (Zn) against oxidative stress complications and disturbances in gene expression in rats treated with CCl4. WP-NPs were used to coat Zn at three levels and amino acids content was determined in WP-NPs and the fabrications. Seven groups of male albino rats included the control group, CCl4-treated group (0.5 ml/100 g b.w) and the groups treated with CCl4 plus WP-NPs, Zn and the three Zn-WP-NPs fabrications. Blood and liver samples were collected for different analysis. Particles sizes were 95, 142, 196 and 228 nm and zeta potential values were -95, -114, -85 and -79 for WP-NPs and the three Zn-WP-NPs fabrications, respectively. Twelve amino acids were found in WP-NPs and this number was decreased by increasing Zn content. WP-NPs, Zn and the Zn coated WP-NPs counteracted the disturbances in biochemical, parameters, gene expression and histological changes in CCl4-treated rats and Zn-WP-NPs was more effective at the low dose. It could be concluded that WP-NPs enhance the effect of Zn and can be used for coating Zn in the preparation of Zn supplementation to enhance its effect and counteract the side effect of excess Zn.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Proteínas do Soro do Leite/química , Compostos de Zinco/farmacologia , Administração Oral , Animais , Tetracloreto de Carbono/efeitos adversos , Citratos/administração & dosagem , Citratos/farmacologia , Portadores de Fármacos/química , Fibrose , Fígado/metabolismo , Fígado/patologia , Masculino , Tamanho da Partícula , Ratos Wistar , Compostos de Zinco/administração & dosagem
7.
Res Vet Sci ; 124: 444-451, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29031416

RESUMO

In current study we aimed to coat the PLLA scaffold with zinc (Zn) silicate mineral nanoparticles. Then, using equine adipose-derived stem cells (ASCs) we intended to compare the osteogenic induction potency of Zn silicate mineral-coated PLLA scaffold with uncoated PLLA scaffold and tissue culture plastic (TCPS). Adipose tissues were collected from 3 horses, and isolation of ASCs was achieved by enzymatic digestion. PLLA scaffold was successfully prepared using a phase separation method and coated with Zn silicate mineral nanoparticles. The coating efficiency was then characterized by scanning electron microscopy and further evaluated with the application of fourier transform infrared microscopic imaging. Viability and growth characteristics of ASCs on TCPS, uncoated and coated PLAA scaffolds were investigated by MTT assay. Alizarin Red staining was performed for determination of calcium deposition following the osteogenic induction. Furthermore, other common osteogenic markers such as alkaline phosphatase (ALP) activity, calcium content, as well as osteogenic (Runx2, ALP, osteonectin, and collagen I) marker genes were also evaluated. Our data showed that Zn silicate mineral nanoparticles was coated successfully on PLLA scaffold and such scaffold had no detrimental effect on cell growth rate as indicated by MTT assay. Moreover, ASCs that differentiated on Zn silicate mineral-coated PLLA scaffold indicated higher ALP activity, more calcium content, and higher expression of bone-related genes than that on uncoated PLLA scaffold and TCPS. Adequate proliferation rate and higher expression of osteogenic markers of stem cells, provides this scaffold as a suitable substrate to support proliferation and differentiation of ASCs in equine.


Assuntos
Cavalos/crescimento & desenvolvimento , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Osteogênese/efeitos dos fármacos , Silicatos/administração & dosagem , Tecidos Suporte/veterinária , Compostos de Zinco/administração & dosagem , Tecido Adiposo/citologia , Animais , Minerais/administração & dosagem
8.
Biol Trace Elem Res ; 190(2): 535-540, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30414001

RESUMO

The present study was conducted to investigate the effects of different dietary zinc sources on growth performance, survival, and body composition of larval rainbow trout, Oncorhynchus mykiss. A total of 3240 larvae with an average weight of 82.3 ± 11.6 mg were randomly divided into four groups by three replicates and were fed for 70 days. Organic zinc (Zn-proteinate, Bioplex Zn®), mineral zinc (ZnSO4), and nanoparticulate zinc (ZnO-NPs) were each added to the basal diet at 50-mg/kg diet. In all of the zinc-supplemented groups, final body weight (FBW) and weight gain (WG) increased significantly (P < 0.05) compared to the control at the termination of the feeding trial. There was no significant difference in specific growth rate (SGR) in experimental groups. Fish fed with mineral and nanoparticulate zinc, respectively, demonstrated the highest and lowest survival rates (P < 0.05) as compared to other experimental diets. Feed conversion ratio (FCR) significantly decreased (P < 0.05) in groups fed with organic and mineral zinc. There were no significant differences in protein, lipid, moisture, and ash content among fish fed the experimental diets. Fish fed mineral zinc showed the highest (P < 0.05) zinc content in the whole body than the other groups. The data of the present study confirm positive effects of the use of 50 mg kg-1 of zinc sources in early diet to enhance growth performance of rainbow trout larvae.


Assuntos
Larva/efeitos dos fármacos , Nanopartículas/química , Oncorhynchus mykiss/crescimento & desenvolvimento , Compostos Organometálicos/farmacologia , Compostos de Zinco/farmacologia , Ração Animal/análise , Animais , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Nanopartículas/administração & dosagem , Nanopartículas/metabolismo , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/metabolismo , Ganho de Peso/efeitos dos fármacos , Compostos de Zinco/administração & dosagem , Compostos de Zinco/metabolismo
9.
Anticancer Res ; 38(11): 6367-6373, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30396959

RESUMO

BACKGROUND/AIM: Dysgeusia is one of the adverse events frequently affecting patients undergoing cancer chemotherapy. Dysgeusia-induced anorexia could decrease patient's quality of life. The present study was designed to determine whether the zinc-containing compound polaprezinc improves chemotherapy-induced dysgeusia. PATIENTS AND METHODS: The incidence of grade 2 dysgeusia was assessed in 634 patients receiving cancer chemotherapy in outpatient settings during January 2013 and June 2017. Polaprezinc was administered to patients showing grade 2 dysgeusia and the effect was compared with that in patients subjected to follow-up observation. RESULTS: Grade 2 dysgeusia appeared in 80 patients (12.6%), in whom pancreatic cancer and treatment with fluoropyrimidines were significant risks for dysgeusia. Polaprezinc, when administered to patients with grade 2 dysgeusia, significantly shortened the duration of dysgeusia compared with that in the follow-up observation group. Subgroup analysis indicated that polaprezinc was less effective in patients with pancreatic cancer, those receiving gemcitabine, or those whose age was 65 year-old and over. CONCLUSION: Chemotherapy-induced dysgeusia occurred with high frequency in patients with pancreatic cancer or in those receiving fluoropyrimidines. Polaprezinc was highly effective in improving the symptom of dysgeusia, except for patients with pancreatic cancer, those receiving gemcitabine and the elderly.


Assuntos
Antineoplásicos/efeitos adversos , Carnosina/análogos & derivados , Disgeusia/tratamento farmacológico , Compostos Organometálicos/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Administração Oral , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carnosina/administração & dosagem , Carnosina/uso terapêutico , Tratamento Farmacológico , Disgeusia/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/uso terapêutico , Pacientes Ambulatoriais , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem , Compostos de Zinco/administração & dosagem , Compostos de Zinco/uso terapêutico
10.
Int J Mol Sci ; 19(9)2018 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-30231592

RESUMO

In rats, mice, and humans, it is known that zinc deficiency may be related to anemia, and zinc supplementation influences hemoglobin production. Our previous studies indicate that in fish, zinc supplementation stimulates red blood cell (RBC) formation (erythropoiesis). However, it is not clear whether the mechanism of zinc-induced erythropoiesis stimulation in fish also occurs in rats. We induced anemia in rats using phenylhydrazine (PHZ) and injected either saline or ZnSO4 solution. We found that an appropriate amount of zinc stimulated erythropoiesis in the PHZ-induced anemic rats. The effects of ZnSO4 injection were dose-dependent. When the concentration of ZnSO4 was higher than 2.8 mg zinc/kg body weight, the RBC level of the anemic rats increased from 60 ± 7% to 88 ± 10% that of the normal rats in two days. Rat bone marrow cells with or without ZnCl2 supplementation were cultured in suspension in vitro. In the cell culture when the zinc concentration was at 0.3 mM, a 1.6-fold proliferation of nascent immature reticulocytes (new RBCs) was observed after one day. In the rat blood, zinc was combined with serum transferrin to induce erythropoiesis. The stimulation of RBC formation by zinc appears to be common among different animals.


Assuntos
Anemia/tratamento farmacológico , Eritropoese/efeitos dos fármacos , Sulfato de Zinco/uso terapêutico , Zinco/uso terapêutico , Anemia/sangue , Anemia/induzido quimicamente , Animais , Células Cultivadas , Cloretos/administração & dosagem , Cloretos/uso terapêutico , Eritrócitos/efeitos dos fármacos , Masculino , Fenil-Hidrazinas , Ratos , Ratos Sprague-Dawley , Reticulócitos/efeitos dos fármacos , Baço , Zinco/administração & dosagem , Compostos de Zinco/administração & dosagem , Compostos de Zinco/uso terapêutico , Sulfato de Zinco/administração & dosagem
11.
Biometals ; 31(5): 821-834, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29974287

RESUMO

Ischaemia-reperfusion injury (IRI) during various surgical procedures, including partial nephrectomy for kidney cancer or renal transplantation, is a major cause of acute kidney injury and chronic kidney disease. Currently there are no drugs or methods for protecting human organs, including the kidneys, against the peril of IRI. The aim of this study was therefore to investigate the reno-protective effect of Zn2+ preconditioning in a clinically relevant large animal sheep model of IRI. Further the reno-protective effectiveness of Zn2+ preconditioning was tested on normal human kidney cell lines HK-2 and HEK293. Anaesthetised sheep were subjected to uninephrectomy and 60 min of renal ischaemia followed by reperfusion. Sheep were preconditioned with intravenous injection of zinc chloride prior to occlusion. Serum creatinine and urea were measured before ischaemia and for 7 days after reperfusion. HK-2 and HEK293 cells were subjected to in vitro IRI using the oxygen- and glucose-deprivation model. Zn2+ preconditioning reduced ischaemic burden determined by creatinine and urea rise over time by ~ 70% in sheep. Zn2+ preconditioning also increased the survival of normal human kidney cells subjected to cellular stress such as hypoxia, hydrogen peroxide injury, and serum starvation. Overall, our protocol incorporating specific Zn2+ dosage, number of dosages (two), time of injection (24 and 4 h prior), mode of Zn2+ delivery (IV) and testing of efficacy in a rat model, a large preclinical sheep model of IRI and cells of human origin has laid the foundation for assessment of the benefit of Zn2+ preconditioning for human applications.


Assuntos
Cloretos/farmacologia , Modelos Animais de Doenças , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Ovinos , Compostos de Zinco/farmacologia , Animais , Cloretos/administração & dosagem , Cloretos/análise , Células HEK293 , Humanos , Peróxido de Hidrogênio , Espectrometria de Massas , Traumatismo por Reperfusão/induzido quimicamente , Traumatismo por Reperfusão/metabolismo , Compostos de Zinco/administração & dosagem , Compostos de Zinco/análise
12.
JAMA Ophthalmol ; 136(9): 1008-1014, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29978186

RESUMO

Importance: A hemodynamic role in the pathogenesis of age-related macular degeneration (AMD) has been proposed, but to our knowledge, an association between retinal vasculature and late AMD has not been investigated. Objective: To determine whether the presence and location of a cilioretinal artery may be associated with the risk of late AMD in the Age-Related Eye Disease Study (AREDS). Design, Setting, and Participants: Retrospective analysis of prospective, randomized clinical trial data from 3647 AREDS participants. Fundus photographs of AREDS participants were reviewed by 2 masked graders for the presence or absence of a cilioretinal artery and whether any branch extended within 500 µm of the central macula. Multivariate regressions were used to determine the association of the cilioretinal artery and vessel location, adjusted for age, sex, and smoking status, with the prevalence of choroidal neovascularization (CNV) or central geographic atrophy (CGA) and AMD severity score for eyes at randomization and progression at 5 years. Main Outcomes and Measures: Association of cilioretinal artery with prevalence and 5-year incidence of CNV or CGA. Results: Among AREDS participants analyzed, mean (SD) age was 69.0 (5.0) years, with 56.3% female, 46.6% former smokers, and 6.9% current smokers. A total of 26.9% of patients had a cilioretinal artery in 1 eye, and 8.4% had the vessel bilaterally. At randomization, eyes with a cilioretinal artery had a lower prevalence of CNV (5.0% vs 7.6%; OR, 0.66; 95% CI, 0.51-0.85; P = .001) but no difference in CGA (1.1% vs 0.8%; OR, 1.33; 95% CI, 0.76-2.32; P = .31). In eyes without late AMD, those with a cilioretinal artery also had a lower mean (SD) AMD severity score (3.00 [2.35] vs 3.19 [2.40]; P = .02). At 5 years, eyes at risk with a cilioretinal artery had lower rates of progression to CNV (4.1% vs 5.5%; OR, 0.75; 95% CI, 0.56-1.00; P = .05) but no difference in developing CGA (2.2% vs 2.7%; OR, 0.83; 95% CI, 0.56-1.23; P = .35) or change in AMD severity score (0.65 [1.55] vs 0.73 [1.70]; P = .11). In patients with a unilateral cilioretinal artery, eyes with the vessel showed a lower prevalence of CNV than fellow eyes (4.7% vs 7.2%; P = .01). Conclusions and Relevance: The presence of a cilioretinal artery is associated with a lower risk of developing CNV, but not CGA, suggesting a possible retinal hemodynamic contribution to the pathogenesis of neovascular AMD. Trial Registration: ClinicalTrials.gov Identifier: NCT00000145.


Assuntos
Neovascularização de Coroide/fisiopatologia , Artérias Ciliares/fisiologia , Atrofia Geográfica/fisiopatologia , Artéria Retiniana/fisiologia , Degeneração Macular Exsudativa/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/uso terapêutico , Ácido Ascórbico/administração & dosagem , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Feminino , Atrofia Geográfica/diagnóstico , Atrofia Geográfica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Acuidade Visual/fisiologia , Vitamina E/administração & dosagem , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico , Compostos de Zinco/administração & dosagem , beta Caroteno/administração & dosagem
13.
Yakugaku Zasshi ; 138(6): 773-780, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-29863045

RESUMO

 Mohs' paste (MP), which is widely used in medical services as a specific hospital preparation, has been considered to have demerits, such as increased hardness after preparation and marked adhesiveness. However, factors associated with variations in its physical properties have not yet been clarified. Therefore, we conducted studies to clarify the physicochemical phenomena influencing such variations, and also examined prescription drug designs of MP preparations that are difficult to use clinically due to the above-mentioned demerits, with a view to improving their usability. Furthermore, with cooperation from the director of the Department of Palliative Care and Maintenance Therapy and certified wound ostomy and continence (WOC) nurses of Yokohama Minami Kyousai Hospital, we clinically applied an improved form of MP I. We also examined the effects of an improved MP II (designed as a stable formulation) in mice. This is an example of the clinical application of basic research to design a new clinical formulation in order to meet medical needs.


Assuntos
Fenômenos Químicos , Cloretos/administração & dosagem , Composição de Medicamentos , Preparações Farmacêuticas , Compostos de Zinco/administração & dosagem , Animais , Cloretos/farmacocinética , Desenho de Drogas , Feminino , Humanos , Camundongos , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II , Sorbitol , Compostos de Zinco/farmacocinética
14.
J Cell Physiol ; 233(11): 8677-8690, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29761825

RESUMO

Oxidative stress is a major factor involved in the pathogenesis of renal ischemia/reperfusion (I/R). Exogenous zinc (Zn) was suggested as a potent antioxidant; however, the mechanism by which it strengthens the organ resistance against the effects of reactive oxygen species (ROS) is not yet investigated. The present study aims to determine whether acute zinc chloride (ZnCl2 ) administration could attenuate endoplasmic reticulum (ER) stress, autophagy, and inflammation after renal I/R. Rats were subjected to either sham operation (Sham group, n = 6), or 1 hr of bilateral ischemia followed by 2 hr of reperfusion (I/R groups, n = 6), or they received ZnCl2 orally 24 hr and 30 min before ischemia (ZnCl2 group, n = 6). Rats were subjected to 1 hr of bilateral renal ischemia followed by 2 hr of reperfusion (I/R group, n = 6). Our results showed that ZnCl2 enhances renal function and reduces cytolysis (p < 0,05). In addition, it increased significantly the activities of antioxidant enzymes (SOD, CAT, and GPX) and the level of GSH in comparison to I/R (p < 0,05). Interestingly, ZnCl2 treatment resulted in significant decreased ER stress, as reflected by GRP78, ATF-6,p-eIF-2α, XPB-1, and CHOP downregulaion. Rats undergoing ZnCl2 treatment demonstrated a low expression of autophagy parameters (Beclin-1 and LAMP-2), which was correlated with low induction of apoptosis (caspase-9, caspase-3, and p-JNK), and reduction of inflammation (IL-1ß, IL-6, and MCP-1) (p < 0,05). In conclusion, we demonstrated the potential effect of Zn supplementation to modulate ER pathway and autophagic process after I/R.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Cloretos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Compostos de Zinco/administração & dosagem , Lesão Renal Aguda/genética , Lesão Renal Aguda/fisiopatologia , Animais , Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Autofagia/genética , Estresse do Retículo Endoplasmático/genética , Humanos , Rim/metabolismo , Rim/patologia , Masculino , Ratos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
16.
Biol Trace Elem Res ; 182(2): 257-264, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28689237

RESUMO

The objective of this study was to investigate the effects of different sources and levels of zinc (Zn) on growth performance, nutrient digestibility, serum biochemical parameters, and fur quality in growing-furring male mink. Animals in the control group were fed a basal diet with no Zn supplementation. Mink in the other nine treatments were fed the basal diet supplemented with Zn from either grade Zn sulfate (ZnSO4·7H2O), Zn glycinate (ZnGly), or Zn pectin oligosaccharides (ZnPOS) at concentrations of either 100, 300, or 900 mg Zn/kg dry matter. One hundred and fifty healthy 15-week-old male mink were randomly allocated to ten dietary treatments (n = 15/group) for a 60-day trial from mid-September to pelting in December. Mink in the Zn-POS groups had higher average daily gain than those in the control group (P < 0.05). Zn source slightly improved the feed/gain (P = 0.097). N retention was increased by Zn addition (P < 0.05). Mink supplemented with dietary Zn had higher (P < 0.05) pancreas Zn level than the control group. Fur length was greater (P < 0.05) in ZnGly and ZnPOS groups compared with the control. In addition, fur length and fur density increased (linear, P < 0.05) with Zn supplementation in the diet. In conclusion, our data show that dietary Zn addition improves growth performance by increasing nitrogen retention and fat digestibility in growing-furring mink and Z-POS is equally bioavailable to mink compared to ZnGly.


Assuntos
Pelo Animal/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Compostos de Zinco/farmacologia , Ração Animal/análise , Animais , Disponibilidade Biológica , Suplementos Nutricionais , Glicina/administração & dosagem , Glicina/análogos & derivados , Glicina/farmacocinética , Glicina/farmacologia , Masculino , Vison , Oligossacarídeos/administração & dosagem , Oligossacarídeos/farmacocinética , Oligossacarídeos/farmacologia , Pectinas/administração & dosagem , Pectinas/farmacocinética , Pectinas/farmacologia , Distribuição Aleatória , Fatores de Tempo , Compostos de Zinco/administração & dosagem , Compostos de Zinco/farmacocinética
17.
Contrast Media Mol Imaging ; 2017: 4945680, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29114176

RESUMO

The purpose of this study was to investigate if a novel parameter, the stress-to-rest ratio of the signal-to-noise ratio (RSNR) obtained with a cadmium zinc telluride (CZT) SPECT scanner, could be used to distinguish triple-vessel disease (TVD) patients. Methods. One hundred and two patients with suspected coronary artery disease were retrospectively involved. Each subject underwent a Tl-201 SPECT scan and subsequent coronary angiography. Subjects were separated into TVD (n = 41) and control (n = 61) groups based on coronary angiography results using 50% as the stenosis cutoff. The RSNR was calculated by dividing the stress signal-to-noise ratio (SNR) by the rest SNR. Summed scores were calculated using quantitative perfusion SPECT (QPS) for all subjects. Results. The RSNR in the TVD group was found to be significantly lower than that in the control group (0.83 ± 0.15 and 1.06 ± 0.17, resp.; P < 0.01). Receiver-operating characteristic (ROC) analysis showed that RSNR can detect TVD more accurately than the summed difference score with higher sensitivity (85% versus 68%), higher specificity (90% versus 72%), and higher accuracy (88% versus 71%). Conclusion. The RSNR may serve as a useful index to assist the diagnosis of TVD when a fully automatic quantification method is used in CZT-based SPECT studies.


Assuntos
Compostos de Cádmio/administração & dosagem , Meios de Contraste/administração & dosagem , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Teste de Esforço , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Telúrio/administração & dosagem , Compostos de Zinco/administração & dosagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão Sinal-Ruído
18.
Biochem Biophys Res Commun ; 494(3-4): 581-586, 2017 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-29111324

RESUMO

Variants of the SHANK3 gene, which encodes a core scaffold protein of the postsynaptic density of excitatory synapses, have been causally associated with numerous brain disorders. Shank3 proteins directly bind zinc ions through their C-terminal sterile α motif domain, which enhances the multimerization and synaptic localization of Shank3, to regulate excitatory synaptic strength. However, no studies have explored whether zinc affects the protein interactions of Shank3, which might contribute to the synaptic changes observed after zinc application. To examine this, we first purified Shank3 protein complexes from mouse brain synaptosomal lysates that were incubated with different concentrations of ZnCl2, and analyzed them with mass spectrometry. We used strict criteria to identify 71 proteins that specifically interacted with Shank3 when extra ZnCl2 was added to the lysate. To characterize the zinc-induced Shank3 interactome, we performed various bioinformatic analyses that revealed significant associations of the interactome with subcellular compartments, including mitochondria, and brain disorders, such as bipolar disorder and schizophrenia. Together, our results showing that zinc affected the Shank3 protein interactions of in vitro mouse synaptosomes provided an additional link between zinc and core synaptic proteins that have been implicated in multiple brain disorders.


Assuntos
Encefalopatias/metabolismo , Cloretos/administração & dosagem , Doenças Mitocondriais/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Mapas de Interação de Proteínas/fisiologia , Proteoma/metabolismo , Sinaptossomos/metabolismo , Compostos de Zinco/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Humanos , Metaboloma/efeitos dos fármacos , Metaboloma/fisiologia , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteoma/efeitos dos fármacos , Sinaptossomos/efeitos dos fármacos
19.
Nutrients ; 9(10)2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29053582

RESUMO

Zinc is an essential component of the insulin granule and it possibly modulates insulin secretion and signaling. Since insulin resistance is a hallmark in the development of type 2 diabetes mellitus, this study aimed at investigating if zinc supplementation is able to improve glucose tolerance and ß-cell function in a model of insulin resistance. Male C57BL/6 mice were distributed in four groups according to the diet: normal fat (NF); normal fat supplemented with ZnCl2 (NFZ); high-fat (HF); and, high-fat chow supplemented with ZnCl2 (HFZ). Intraperitoneal glucose (ipGTT) and insulin (ipITT) tolerance, glycemia, insulinemia, HOMA-IR, and HOMA-ß were determined after 15 weeks in each diet. Glucose-stimulated insulin secretion (GSIS) was investigated in isolated islets. The insulin effect on glucose uptake, metabolism, and signaling was investigated in soleus muscle. ZnCl2 did not affect body mass or insulin sensitivity as assessed by ipITT, HOMA-IR, muscle glucose metabolism, and Akt and GSK3-ß phosphorylation. However, glucose tolerance, HOMA-ß, and GSIS were significantly improved by ZnCl2 supplementation. Therefore, ZnCl2 supplementation improves glucose homeostasis in high fat-fed mice by a mechanism that enhances ß-cell function, rather than whole-body or muscle insulin sensitivity.


Assuntos
Glicemia/metabolismo , Dieta Hiperlipídica , Homeostase/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Zinco/administração & dosagem , Animais , Cloretos/administração & dosagem , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Modelos Animais de Doenças , Hemoglobina A Glicada/metabolismo , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Insulina/sangue , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Zinco/sangue , Compostos de Zinco/administração & dosagem
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