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1.
Int J Nanomedicine ; 15: 2733-2749, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368052

RESUMO

Background: This study demonstrated an innovative formulation including the polyprenol (GBP) lipid and vitamin E-TPGS hybrid nanoparticles (NPs) which was aimed to control the transfer of betulinic acid (BA) and low-substituted hydroxyl fullerenol (C60(OH)n). Additionally, it developed BA-C60(OH)n-GBP-TPGS-NPs delivery system and researched the anti-hepatocellular carcinoma (HCC) effects. Materials and Methods: The NPs were prepared by nanoprecipitation with ultrasonic-assisted emulsification (UAE) method. It was characterized by scanning electronic microscopy (SEM), transmission electron microscopy (TEM), FTIR spectrum, size distribution and zeta potential. Physical and chemical properties were evaluated through measurement of drug release, stability studies, drug loading efficiency (DE) and encapsulation efficiency (EE). Biological activities were evaluated through measurement of MTT assay, lactate dehydrogenase leakage assay (LDH), cell proliferation assays, cell apoptosis analysis, comet assay, wound healing assay, cell invasion and Western blot analysis. Results and Conclusions: The NPs exhibited clear distribution characteristics, improved solubility and stability. BA and C60(OH)n for the NPs displayed a biphasic release pattern with sustained drug release properties. The mixture of C60(OH)n with different hydroxyl groups may have a certain effect on the stability of the NPs system itself. The NPs could effectively inhibit MHCC97H cell proliferation, migration and invasion in vitro. Combined use of C60(OH)n and BA in GBP lipids may improve the inhibit effect of C60(OH)n or BA against HCC cells and reduce cytotoxicity and genotoxicity of C60(OH)n for normal cells. We concluded that one of the important mechanisms of BA-C60(OH)n-GBP-TPGS-NPs inhibiting MHCC97H cells is achieved by up-regulating the expression of Caspase-3, Caspase-8 and Caspase-9.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Fulerenos/farmacocinética , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Triterpenos/farmacocinética , Vitamina E/toxicidade , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Fulerenos/administração & dosagem , Fulerenos/química , Humanos , Lipídeos/química , Neoplasias Hepáticas/patologia , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanopartículas/administração & dosagem , Poliprenois/química , Triterpenos/administração & dosagem , Vitamina E/química
3.
Environ Sci Pollut Res Int ; 27(18): 23026-23034, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32329006

RESUMO

The present study aimed to investigate the possible mitigating effect of L-carnitine (LC) and/or α-tocopherol (Vit. E) administration against tilmicosin (TIL)-induced cardiotoxicity in rats. Fifty-six male albino rats were divided into seven groups according to LC, Vit. E, and/or TIL administration. Control, LC, and Vit. E groups were given saline, 150 mg LC/kg body weight (BW)/day and 100 mg Vit. E/kg BW/day, respectively, orally once daily for 15 days. The TIL group was administered saline orally once daily for 15 days and a single dose of TIL (75 mg/kg BW) subcutaneously (SC) on day 14 from the starting of the experimental period (15 days). The TIL-LC, TIL-Vit. E, and TIL-LC-Vit. E groups received 150 mg LC/kg BW/day, 100 mg Vit. E/kg BW/day, and 150 mg LC/kg BW pulse 100 mg Vit. E/kg BW, respectively, orally once daily for 15 days with TIL as described above. The results revealed that the administration of TIL significantly (P ≤ 0.05) raised serum activities of heart injury indicators, lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB with substantial increase (P ≤ 0.05) in the cardiac contents of malondialdehyde (MDA) and decreased in antioxidants. The pathological changes appeared in the form of necrotic muscle fibers and massive inflammatory cellular infiltrations in the cardiac muscle and increased the caspase-3 immunohistochemical expression in the heart tissues as well. These changes were ameliorated by LC and/or Vit. E administration. In conclusion, supplementation of LC and/or Vit. E ameliorated the cardiotoxicity of the TIL SC injection in the rat.


Assuntos
Carnitina , Vitamina E , Animais , Antioxidantes , Cardiotoxicidade , Masculino , Estresse Oxidativo , Ratos , Tilosina/análogos & derivados
4.
Expert Opin Pharmacother ; 21(8): 953-967, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32237916

RESUMO

INTRODUCTION: There is an unmet medical need for an effective anti-fibrotic treatment for NASH with advanced fibrosis. AREAS COVERED: The authors review the current and novel agents for the treatment of NASH with fibrosis. They also consider the potential future strategies of combination therapies. EXPERT OPINION: Farnesoid X receptor (FXR) agonist (obeticholic acid [OCA]) significantly ameliorated hepatic fibrosis in NASH stage 2/3 fibrosis in an interim analysis of phase 3 trial. Because OCA has several drawbacks such as itching and elevated low-density lipoprotein-cholesterol (LDL-C), non-bile acid FXR agonists are now under development. Selonsertib (apoptosis signaling kinase 1 inhibitor), emricasan (an irreversible pan-caspase inhibitor), and simtsuzumab (a monoclonal antibody against lysyl oxidase-like 2) were discontinued because of no efficacy over placebo. Peroxisome proliferator-activator receptor α/δ agonists, C-C motif chemokine receptor-2/5 antagonists, and thyroid ß receptor agonist are ongoing in phase 3 trials. A variety of agents including fibroblast growth factor (FGF)-21 and FGF-19 agonists, as well as acetyl-CoA carboxylase inhibitors, are also expected. Among antidiabetic agents, semaglutide, a novel GLP-1 RA, is ongoing for NASH stage 1-3 fibrosis in a phase 2 trial. Furthermore, the combination of GLP-RA/glucagon receptor agonist and GLP-RA/gastrointestinal peptide agonist are promising future options.


Assuntos
Ácido Quenodesoxicólico/análogos & derivados , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Pioglitazona/uso terapêutico , Vitamina E/uso terapêutico , Ácido Quenodesoxicólico/administração & dosagem , Ácido Quenodesoxicólico/uso terapêutico , Ensaios Clínicos como Assunto , Fatores de Crescimento de Fibroblastos/agonistas , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Pioglitazona/administração & dosagem , Receptores Citoplasmáticos e Nucleares/agonistas , Resultado do Tratamento , Vitamina E/administração & dosagem
5.
Int. j. morphol ; 38(2): 278-288, abr. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1056435

RESUMO

This experiment was designed to study the effects of oral administration of artemether which is the most rapid-acting class of antimalarial drugs and the possible protective effect of vitamin E taken with it on the liver of albino rats. A total of twenty-four adult male albino rats were used in this study and were divided into four groups. Group one served as a control and rats in group two exposed to oral intake of artemether daily for fifteen days. The third and fourth groups treated with artemether plus low and high doses of vitamin E respectively. At the end of the experiment, the rats were sacrificed, and the livers were obtained and processed for histological, biochemical and statistical studies. Histological study of the hepatocytes of rats exposed to artemether showed nearly complete disintegration of most cellular contents except few numbers of mitochondria and rough endoplasmic reticulum. Also, the cytoplasm of these cells had few lysosomes, many vacuoles and irregular nuclei with abnormal distribution of chromatin and were shown. The hepatic sinusoids were dilated and filled with blood and vacuoles and bile ductules were abnormal in its structure. Treatment with low and high doses of vitamin E in concomitant with artemether ameliorated the hepatic histopathological lesions and its parenchyma attained nearly normal structure. As far as biochemical changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats treated with artemether were significantly elevated as compared to the control. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were significantly increased in the liver in rats treated with artemether. However, vitamin E ameliorated the rise in ALT and AST with decreased MDA concentration and levels of SOD as compared to the corresponding artemether group values. Results of the present suggest that artemether has a harmful and stressful effect on hepatic tissue and the treatment with vitamin E may alleviate this toxicity.


Este experimento fue diseñado para estudiar los efectos de la administración oral de arteméter, la clase de medicamentos antipalúdicos de acción rápida, y el posible efecto protector de la vitamina E en el hígado de ratas albinas. Se utilizaron un total de 24 ratas albinas machos adultas y se dividieron en cuatro grupos. El grupo uno sirvió como control y las ratas en el grupo dos recibieron la dosis oral de arteméter diariamente durante 15 días. Los grupos tres y cuatro fueron tratados con arteméter, más dosis bajas y altas de vitamina E, respectivamente. Al final del experimento, se sacrificaron las ratas y se obtuvieron y procesaron los hígados para estudios histológicos, bioquímicos y estadísticos. El estudio histológico de los hepatocitos de ratas expuestas a arteméter mostró una desintegración casi completa de la mayoría de los contenidos celulares, excepto algunos mitocondrias y retículo endoplásmico rugoso. Además, el citoplasma de estas células tenía pocos lisosomas, muchas vacuolas y núcleos irregulares con distribución anormal de cromatina. Los sinusoides hepáticos estaban dilatados y llenos de sangre y vacuolas, y los conductos biliares tenían una estructura anormal. El tratamiento con dosis bajas y altas de vitamina E en forma concomitante con arteméter mejoró las lesiones histopatológicas hepáticas y su parénquima alcanzó una estructura casi normal. En cuanto a los cambios bioquímicos, la alanina aminotransferasa (ALT) y la aspartato aminotransferasa (AST) en ratas tratadas con arteméter se elevaron significativamente en comparación con el control. Los niveles de superóxido dismutasa (SOD) y malondialdehído (MDA) aumentaron significativamente en el hígado en ratas tratadas con arteméter. Sin embargo, la vitamina E mejoró el aumento de ALT y AST con una disminución de la concentración de MDA y los niveles de SOD en comparación con los valores correspondientes del grupo de arteméter. Los resultados del presente estudio sugieren que el arteméter tiene un efecto dañino y estresante sobre el tejido hepático y el tratamiento con vitamina E puede aliviar esta toxicidad.


Assuntos
Animais , Masculino , Ratos , Vitamina E/farmacologia , Artemisininas/toxicidade , Doença Hepática Crônica Induzida por Substâncias e Drogas/enzimologia , Aspartato Aminotransferases/análise , Vitamina E/administração & dosagem , Microscopia Eletrônica de Transmissão , Alanina Transaminase/análise , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Antimaláricos/toxicidade
6.
Int. j. morphol ; 38(2): 461-471, abr. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1056463

RESUMO

This experiment was designed to study the administration of normal doses of one of recent antimalarial drug and coadministration of vitamin E on the kidney tissue. A total twenty-four adult male albino rats were used and divided into four groups: the first one served as a control, the second received artemether orally for three days consecutively. The rats of the third and fourth groups received the same dose of artemether concomitantly with 50 and 100 mg/kg vitamin E orally daily for 2 weeks. After the last dose, the rats were sacrificed and the kidney tissues with blood samples obtained and processed for light, electron microscopic and biochemical analysis. Histologically, artemether treated kidneys showed atrophied glomeruli with widened urinary space and kidney tubules were degenerated with disturbed contour and some vacuoles inside it. Ultrastructurally, the glomeruli of this group showed hypertrophic endothelial cells, irregularity of its basement membrane, disrupted foot processes and filtration slits. The kidney tubule cells showed loss of basal infoldings, cytoplasmic vacuolation, polymorphic damaged swollen mitochondria a loss of its microvilli towards its capillary lumen. Artemether plus vitamin E of the rat kidney groups showed improvement of morphological changes compared to the changes seen in artemether alone. These data were confirmed by biochemical findings with marked improvement of blood urea and creatinine levels and increase of anti-oxidant enzyme activities of glutathione peroxidase and superoxide dismutase in the vitamin E treated groups. The results of this study revealed that vitamins E can improve the adverse changes of artemether of rat renal tissue.


Este proyecto fue diseñado para estudiar la administración de dosis normales de uno de los medicamentos antipalúdicos y de la administración de vitamina E en el tejido renal. Se utilizaron 24 ratas albinas machos adultas divididas en cuatro grupos: el primero sirvió como control, el segundo recibió arteméter por vía oral durante tres días consecutivos. Las ratas del tercer y cuarto grupos recibieron la misma dosis de arteméter concomitantemente con 50 y 100 mg / kg de vitamina E por vía oral diariamente durante 2 semanas. Después de la última dosis, las ratas fueron sacrificadas y se obtuvo el tejido renal de cada muestra los cuales fueron procesados para análisis con microscopías de luz y electrónica, además de exámenes bioquímicos. Histológicamente, los riñones tratados con arteméter mostraron atrofia glomerular con espacio urinario ensanchado y túbulos renales degenerados con contorno alterado y algunas vacuolas en su interior. Ultraestructuralmente, los glomérulos de este grupo mostraron células endoteliales hipertróficas, irregularidad de su membrana basal, procesos alterados del pie y hendiduras de filtración. Las células del túbulo renal mostraron pérdida de inflexiones basales, vacuolación citoplasmática, mitocondrias dañadas y pérdida de sus microvellosidades hacia la luz capilar. Arteméter más vitamina E en los grupos de riñón de rata mostraron una mejora de los cambios morfológicos, en comparación con los cambios observados en arteméter solamente. Estos datos fueron confirmados por hallazgos bioquímicos con una marcada mejoría de los niveles de urea y creatinina en sangre y un aumento de las actividades enzimáticas antioxidantes de la glutatión peroxidasa y la superóxido dismutasa en los grupos tratados con vitamina E. Los resultados de este estudio revelaron que la vitamina E puede mejorar los cambios adversos del arteméter del tejido renal de la rata.


Assuntos
Animais , Masculino , Ratos , Vitamina E/farmacologia , Lesão Renal Aguda/induzido quimicamente , Artemeter/toxicidade , Vitamina E/administração & dosagem , Microscopia Eletrônica , Biomarcadores/análise , Ratos Wistar , Rim/efeitos dos fármacos , Rim/patologia , Rim/ultraestrutura , Antimaláricos/toxicidade
7.
Mutat Res ; 850-851: 503150, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247559

RESUMO

Extremely low frequency electromagnetic fields have been classified as a possible human carcinogen by the International Agency for Research on Cancer and this has raised some concern about its health effects on employees extensively exposed to these fields at thermal power plants. In this study, the effect of using vitamin E and C supplements have been examined on employees working at a thermal power plant. In this randomized controlled, double-blind clinical trial, 81 employees from different parts of the thermal power plant were enrolled between July and November 2017, and divided into four groups: Group 1 received vitamin E (400 units/day), Group 2: vitamin C (1000 mg/day), Group 3: vitamin E + C and Group 4: no intervention. DNA damage was measured in peripheral blood lymphocytes using comet assay and apoptosis, using flow cytometry. Based on the results, tail intensity and tail length in the vitamin E group, and all comet assay indices in the vitamin E + C and vitamin C groups (except DNA damage index) significantly decreased after the intervention, while the comet assay indices did not change significantly in the control group. None of the flow cytometry indices including early apoptosis, late apoptosis and necrosis changed after intervention in either group. The use of antioxidant vitamins such as E and C, can increase the activity of the non-enzymatic antioxidant defense system, and protect DNA from damage caused by exposure to extremely low frequency magnetic fields. But, taking these vitamins has no effect on apoptosis. It seems that consumption of vitamin E affected all investigated comet assay indices and can be probably considered as the best intervention.


Assuntos
Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Dano ao DNA/efeitos dos fármacos , Vitamina E/administração & dosagem , Adulto , Apoptose/efeitos dos fármacos , Dano ao DNA/genética , Método Duplo-Cego , Citometria de Fluxo , Humanos , Irã (Geográfico) , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Campos Magnéticos/efeitos adversos , Masculino , Centrais Elétricas
8.
MMWR Morb Mortal Wkly Rep ; 69(9): 236-240, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32134907

RESUMO

On July 10, 2019, Wisconsin Department of Health Services (WDHS) was notified of five previously healthy adolescents with severe lung injuries who reported use of e-cigarette, or vaping, products before symptom onset. As of December 31, 2019, 105 confirmed or probable cases of e-cigarette, or vaping, product use-associated lung injury (EVALI)* had been reported to WDHS . Three social clusters (A, B, and C), comprising eight EVALI patients (cluster A = two patients, cluster B = three, and cluster C = three) were identified. WDHS investigated these clusters with standard and follow-up interviews; laboratory analysis of e-cigarette, or vaping, products; and analysis of bronchoalveolar lavage (BAL) fluid. All eight patients reported daily use of tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, product cartridges (THC cartridges) in the month preceding symptom onset. All THC cartridges were purchased from local illicit dealers, and all patients reported using THC cartridges labeled as "Dank Vapes," among other illicit brand names. At least two members of each cluster reported frequent sharing of THC cartridges before symptom onset. All eight patients also reported daily use of nicotine-containing e-cigarette, or vaping, products. Vitamin E acetate (VEA) was detected in all five THC cartridges tested from two patients, and in BAL fluid from two other patients. These findings suggest that THC cartridges containing VEA and sold on the illicit market were likely responsible for these small clusters of EVALI. Based on information presented in this and previous reports (1,2) CDC recommends not using THC-containing e-cigarette, or vaping, products, especially those obtained from informal sources such as friends, family, or in-person or online dealers (1). VEA is strongly linked to the EVALI outbreak and should not be added to e-cigarette, or vaping, products (1).


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Lesão Pulmonar/epidemiologia , Vaping/efeitos adversos , Adolescente , Análise por Conglomerados , Dronabinol/toxicidade , Feminino , Humanos , Masculino , Vaping/psicologia , Vitamina E/toxicidade , Wisconsin/epidemiologia , Adulto Jovem
9.
Cochrane Database Syst Rev ; 3: CD002141, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32130738

RESUMO

BACKGROUND: This is the second update of this Cochrane Review. Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer. OBJECTIVES: To determine whether vitamins and minerals and other potential agents, alone or in combination, reduce lung cancer incidence and lung cancer mortality in healthy populations. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer. DATA COLLECTION AND ANALYSIS: Four review authors independently selected the trials to be included in the review, assessed their methodological quality and extracted data. For dichotomous outcomes we calculated risk ratios (RRs) and 95% confidence intervals (CIs) and pooled results using the random-effects model. We assessed the risk of bias using Cochrane's 'Risk of bias' assessment tool and certainty of evidence using the GRADE approach. MAIN RESULTS: In this update, we identified three new trials for a total of 12 studies. Six analysed vitamin A, three vitamin C, three combined vitamin D3 + calcium, four vitamin E combined with other products, one selenium supplements and nine studied combinations of two or more products. Four studies included only men and five only women. Vitamin A results in little to no difference in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19; 5 RCTs, 212314 participants; high-certainty evidence) and lung cancer mortality (RR 1.06, 95% CI 0.81 to 1.38; 3 RCTs, 190118 participants; high-certainty evidence). But in smokers or asbestos workers vitamin A increases the risk of lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 RCTs, 43995 participants; high-certainty evidence), lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38; 2 RCTs, 29426 participants; high-certainty evidence) and all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 RCTs, 32883 participants; high-certainty evidence). Vitamin A increases the risk of minor side effects, such as yellowing of the skin and minor gastrointestinal symptoms (high-certainty evidence). Vitamin C likely results in little to no difference in lung cancer incidence (RR 1.29, 95% CI 0.67 to 2.49; 2 RCTs, 14953 participants; moderate-certainty evidence). In women, vitamin C increases the risk of lung cancer incidence (RR 1.84, 95% CI 1.14 to 2.95; 1 RCT, 7627 participants; high-certainty evidence). In men, vitamin C results in little to no difference in mortality for lung cancer (RR 0.81, 95% CI 0.53 to 1.23; 1 RCT, 7326 participants; high-certainty evidence). Vitamin D + calcium may result in little to no difference in lung cancer incidence in postmenopausal women (RR 0.90, 95% CI 0.39 to 2.08; 3 RCTs, 37601 women; low-certainty evidence). Vitamin E results in little to no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 RCTs, 36841 participants; high-certainty evidence) or to lung cancer mortality (RR 0.96, 95% CI 0.77 to 1.18; 2 RCTs, 29214 participants; high-certainty evidence), but increases the risk of haemorrhagic strokes (hazard ratio (HR), 1.74, 95% CI 1.04 to 2.91; 1 RCT, 14641 participants; high-certainty evidence). Calcium results in little to no difference in lung cancer incidence in postmenopausal women (RR 0.65, 95% CI 0.13 to 3.18; 1 RCT, 733 participants) or in risk of renal calculi (RR 1.94, 95% CI 0.20 to 18.57; 1 RCT, 733 participants; low-certainty evidence). Selenium in men results in little to no difference in lung cancer incidence (RR 1.11, 95% CI 0.80 to 1.54; 1 RCT, 17448 participants; high-certainty evidence) and lung cancer mortality (RR 1.09, 95% CI 0.72 to 1.66; 1 RCT, 17448 participants; high-certainty evidence) and increases the risk for grade 1 to 2 dermatitis (RR 1.16, 95% CI 1.04 to 1.31; 1 RCT, 17448 participants; high-certainty evidence) and for alopecia (RR 1.28, 95% CI 1.07 to 1.53; 1 RCT, 17448 participants; high-certainty evidence). The combination of vitamins A, C, E + selenium + zinc results in little to no difference in lung cancer incidence (RR 0.64, 95% CI 0.28 to 1.48; 1 RCT, 12741 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: Well-designed RCTs have shown no beneficial effect of supplements for the prevention of lung cancer and lung cancer mortality in healthy people. Vitamin A supplements increase lung cancer incidence and mortality in smokers or persons exposed to asbestos. Vitamin C increases lung cancer incidence in women. Vitamin E increases the risk of haemorrhagic strokes.


Assuntos
Suplementos Nutricionais , Nível de Saúde , Neoplasias Pulmonares/prevenção & controle , Minerais/uso terapêutico , Vitaminas/uso terapêutico , Ácido Ascórbico/uso terapêutico , Cálcio na Dieta/efeitos adversos , Cálcio na Dieta/uso terapêutico , Colecalciferol/uso terapêutico , Intervalos de Confiança , Feminino , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/mortalidade , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Selênio , Compostos de Selênio/uso terapêutico , Fatores Sexuais , Vitamina A/efeitos adversos , Vitamina A/uso terapêutico , Vitamina E/uso terapêutico , Vitaminas/efeitos adversos , alfa-Tocoferol/efeitos adversos , alfa-Tocoferol/uso terapêutico , beta Caroteno/uso terapêutico
10.
Int J Nanomedicine ; 15: 1469-1480, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184599

RESUMO

Purpose: In spite of its enhanced efficacy and reduced side effects in clinical hepatocellular carcinoma (HCC) therapy, the therapeutic efficacy of antitumor angiogenesis inhibitor sorafenib (SFB) is still restricted due to short in vivo half-life and drug resistance. Here, a novel SFB-loaded dendritic polymeric nanoparticle (NP-TPGS-SFB) was developed for enhanced therapy of HCC. Methods: NP-TPGS-SFB was fabricated by encapsulating SFB with biodegradable dendritic polymers poly(amidoamine)-poly(γ-benzyl-L-Glutamate)-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS). Results: NP-TPGS-SFB exhibited excellent stability and achieved acid-responsive release of SFB. It also exhibited much higher cellular uptake efficiency in HepG2 human liver cells than PEG-conjugated NP (NP-PEG-SFB). Furthermore, MTT assay confirmed that NP-TPGS-SFB induced higher cytotoxicity than NP-PEG-SFB and free SFB, respectively. Lastly, NP-TPGS-SFB significantly inhibited tumor growth in mice bearing HepG2 xenografts, with negligible side effects. Conclusion: Our result suggests that NP-TPGS-SFB may be a novel approach for enhanced therapy of HCC with promising potential.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Dendrímeros/química , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/administração & dosagem , Sorafenibe/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/patologia , Dendrímeros/farmacocinética , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Nanopartículas/química , Polímeros/química , Polímeros/farmacocinética , Vitamina E/química , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Anim Sci ; 98(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32026938

RESUMO

Advances in the understanding of how the immune system functions in response to diet have altered the way we think about feeding livestock and companion animals on both the short (weeks/months) and long-term (years) timelines; however, depth of research in each of these species varies. Work dedicated to understanding how immune function can be altered with diet has revealed additional functions of required nutrients such as vitamins D and E, omega-3 polyunsaturated fatty acids (PUFA), and minerals such as zinc, while feed additives such as phytogenics and probiotics add an additional layer of immunomodulating potential to modern diets. For certain nutrients such as vitamin D or omega-3 PUFA, inclusion above currently recommended levels may optimize immune function and reduce inflammation, while for others such as zinc, additional pharmacological supplementation above requirements may inhibit immune function. Also to consider is the potential to over-immunomodulate, where important functions such as clearance of microbial infections may be reduced when supplementation reduces the inflammatory action of the immune system. Continued work in the area of nutritional immunology will further enhance our understanding of the power of nutrition and diet to improve health in both livestock and companion animals. This review collects examples from several species to highlight the work completed to understand how nutrition can be used to alter immune function, intended or not.


Assuntos
Gado/fisiologia , Estado Nutricional/imunologia , Animais de Estimação/fisiologia , Vitamina D/imunologia , Animais , Dieta/veterinária , Ácidos Graxos Ômega-3/imunologia , Gado/imunologia , Minerais/imunologia , Necessidades Nutricionais , Animais de Estimação/imunologia , Vitamina E/imunologia
13.
Mol Carcinog ; 59(4): 365-389, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017273

RESUMO

α-Tocopherol (α-T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α-T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α-T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α-T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ- and δ-forms of tocopherols and tocotrienols (T3). In comparison with α-T, these forms have much lower systemic bioavailability but have shown stronger cancer-preventive activities in many studies in animal models and cell lines. γ-T3 and δ-T3 generally have even higher activities than γ-T and δ-T. In this article, we review recent results from human and laboratory studies on the cancer-preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.


Assuntos
Antioxidantes/farmacologia , Suplementos Nutricionais , Neoplasias/prevenção & controle , Vitamina E/farmacologia , Animais , Antioxidantes/administração & dosagem , Carcinogênese/efeitos dos fármacos , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Tocoferóis/administração & dosagem , Tocoferóis/classificação , Tocoferóis/farmacologia , Vitamina E/administração & dosagem
14.
Int J Nanomedicine ; 15: 809-819, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32103938

RESUMO

Background and Purpose: The development of multiple drug resistance (MDR) to chemotherapy and single modal therapy remains unsatisfied for the eradication of tumor, which are major obstacles in cancer therapy. This novel system with excellent characteristics for inhibition of P-glycoprotein (P-gp), and for near-infrared fluorescence (NIRF) imaging-guided chemo-photothermal therapy (PTT), has been identified as a promising way to MDR and achieve synergistic cancer therapy. Methods: In this study, we successfully synthesized a multifunctional theranostic system, which was developed through FDA-approved self-assembling drugs, which contain anticancer drug doxorubicin (Dox), imaging and high photothermal conversion drug indocyanine green (ICG) and P-gp regulator TPGS (the system named T/Dox-ICG). We studied the characterization of T/Dox-ICG NPs, including the TEM, SEM, DLS, UV-vis-NIR, zeta potential, CLSM, in vitro FL imaging, in vitro photothermal effect, in vitro Dox and ICG release. We used CLSM to verify the location of intracellular distribution of Dox in SCG 7901/VCR cells, Western blot was performed to demonstrate the TPGS-mediated inhibition of P-gp. And, the cytotoxicity of materials against SCG 7901/VCR cells was studied by the MTT assay. Results: The TEM showed the T/Dox-ICG NPs had good monodispersity with diameters of 19.03 nm, Dox and ICG could be released constantly from T/Dox-ICG NPs in vitro. In vitro cell experiments demonstrated higher Dox accumulation and retention in the nucleus. Western blot showed TPGS could obviously inhibit the expression of P-gp. In vitro cytotoxicity assay showed more significant cytotoxicity on MDR cells (SCG 7901/VCR) with only 8.75% of cells surviving. Conclusion: MDR cancer therapy indicates that it may be important to develop a safer system that can simultaneously inhibit the drug transporters and monitor the delivery of chemotherapeutic agents, and combination therapy have raised widespread concern on tumor treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas/administração & dosagem , Neoplasias Gástricas/terapia , Nanomedicina Teranóstica/métodos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Resistência a Múltiplos Medicamentos , Humanos , Verde de Indocianina/administração & dosagem , Verde de Indocianina/farmacocinética , Nanopartículas/química , Fototerapia/métodos , Neoplasias Gástricas/patologia , Vitamina E/química
15.
Maturitas ; 133: 1-6, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32005419

RESUMO

BACKGROUND AND AIMS: Urinary incontinence (UI) is common in women, with up to 50 % experiencing involuntary loss of urine at some point. Femaxeen®, a formulation containing purified and specific cytoplasmic extracts of pollen, pumpkin seed extract and vitamin E (referred to hereafter as Femaxeen), is indicated for control of UI in women. This study investigated the efficacy and safety of Femaxeen for the prevention and treatment of UI symptoms in women. METHODS: In this randomized, double-blind, placebo-controlled trial, 81 women with moderate, severe, or very severe urge (43.4 %), stress (31.6 %) or mixed (25.0 %) UI were allocated to receive Femaxeen or placebo once daily for 90 days. Treatment efficacy was assessed using three validated questionnaires. FINDINGS: Thirty-eight patients per group were analyzed. Femaxeen produced statistically significant improvements from baseline to Day 90 (p < 0.001 for all comparisons) in scores on the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Measurement of Urinary Handicap (MHU) questionnaire, and Sandvik Incontinence Severity Index. Reduction from baseline in ICIQ-SF and MHU scores at Day 60 and Day 90 was significantly greater with Femaxeen than placebo (p < 0.05 for all comparisons). Femaxeen significantly reduced ICIQ-SF and MHU scores from baseline to Day 60 and Day 90 in all UI types (p < 0.05 for all comparisons except ICIQ-SF scores for stress UI). Femaxeen and placebo were well tolerated. Associated adverse events were few and mild in intensity. CONCLUSIONS: Femaxeen is effective for treating UI, and has a safety profile comparable to that of placebo.


Assuntos
Cucurbita , Extratos Vegetais/uso terapêutico , Pólen , Sementes , Incontinência Urinária/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Vitamina E/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Fitoterapia , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Incontinência Urinária/prevenção & controle
16.
Eur J Ophthalmol ; 30(3): 430-438, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32064920

RESUMO

PURPOSE: A prospective, open-label study in 20 professional swimmers evaluated the efficacy and safety of an ophthalmic solution containing crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS in releasing eye irritation and restoring ocular surface damages after prolonged exposure to chlorinated water. METHODS: Individually, one eye was instilled with the ophthalmic solution and the other used as a comparator. Eye drops were self-administered three times a day for 2 months. Tear film breakup time (primary endpoint), Schirmer I test, beating of eyelashes/min, tear osmolarity, corneal and conjunctival staining with fluorescein, Ocular Surface Disease Index questionnaire, subject satisfaction, visual acuity (secondary endpoints), and Efron Grading Scale were evaluated at screening/baseline (V1), week 1 (V2), week 2 (V3), week 4 (V4), and week 8 (V5). RESULTS: After 2 months, breakup time test significantly improved in the treated eyes (+1.67 s) compared to control (-3.00 s) (p = 0.0002). Corneal and conjunctival surfaces of treated eyes recovered significantly compared to control eyes when assessed by fluorescein staining (p < 0.0001), Ocular Surface Disease Index (p < 0.05), and visual analog scale (p = 0.0348) scores. Improvements were also observed with Schirmer I test, beating of eyelashes, and tear osmolarity, despite without statistical significance. Efron Grading Scale was consistent with the other tests. The ocular tolerability was excellent. CONCLUSION: The adequate combination of crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS, contained in the ophthalmic solution VisuXL®, has been shown to protect ocular surface from potential damages originating from prolonged exposure to chlorinated water. VisuXL may represent a compelling treatment in other situations beyond dry eye syndrome.


Assuntos
Cloraminas/efeitos adversos , Doenças da Túnica Conjuntiva/tratamento farmacológico , Doenças da Córnea/tratamento farmacológico , Ácido Hialurônico/administração & dosagem , Hiperemia/tratamento farmacológico , Ubiquinona/análogos & derivados , Poluentes Químicos da Água/efeitos adversos , Administração Oftálmica , Adolescente , Adulto , Doenças da Túnica Conjuntiva/induzido quimicamente , Doenças da Túnica Conjuntiva/fisiopatologia , Doenças da Córnea/induzido quimicamente , Doenças da Córnea/fisiopatologia , Reagentes para Ligações Cruzadas , Desinfetantes/efeitos adversos , Combinação de Medicamentos , Humanos , Hiperemia/induzido quimicamente , Hiperemia/fisiopatologia , Masculino , Soluções Oftálmicas , Concentração Osmolar , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Piscinas , Lágrimas/química , Lágrimas/fisiologia , Ubiquinona/administração & dosagem , Vitamina E/administração & dosagem , Vitaminas/administração & dosagem , Adulto Jovem
18.
Int J Nanomedicine ; 15: 729-734, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099361

RESUMO

Background: Recently, use of nanotechnology in biomedical applications such as drug delivery and diagnostic and therapeutic tools has increased greatly. This study evaluated gold nanoparticle (GNPs)-induced nephrotoxic effects in rats in vivo, and examined protective effects of alpha-lipoic acid (α-Lip) and Vitamin E (Vit E) against nephrotoxicity, lipid peroxidation, and inflammatory kidney damage induced by GNPs. Materials and Methods: Twenty-four male Wistar-Kyoto rats (220-240 g, 12 weeks old) were dosed with 50 µL of 10 nm GNPs administered intraperitoneally with or without 200 mg/kg/day Vit E or 200 mg/kg/day α-Lip. Serum was prepared for biochemical analyses. Kidney function was evaluated through measurement of creatinine (CR), uric acid (URIC), and blood urea nitrogen (BUN). Oxidative stress and lipid peroxidation were evaluated by measurement of reduced glutathione (GSH) and malondialdehyde (MDA) in kidney tissue homogenates. Results and Conclusions: The results showed a significant rise in serum kidney function biomarkers including urea, URIC, CR, and BUN in GNP-treated rats compared to normal control rats. Furthermore, GNPs led to decreased GSH and elevated MDA levels. Vit E or α-Lip supplementation showed a beneficial effect against nephrotoxicity, lipid peroxidation, and inflammatory kidney damage induced by GNPs. This study suggests that use of natural antioxidants in combination with GNPs may be a useful tool in preventing GNPs toxicity.


Assuntos
Ouro/toxicidade , Inflamação/induzido quimicamente , Peroxidação de Lipídeos/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Ácido Tióctico/farmacologia , Vitamina E/farmacologia , Animais , Biomarcadores/metabolismo , Creatinina/sangue , Glutationa/metabolismo , Inflamação/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Endogâmicos WKY , Ácido Úrico/sangue
19.
Clin Chim Acta ; 505: 31-33, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32084381

RESUMO

BACKGROUND: Vitamin A and E are routinely monitored to assess nutritional status. The most commonly used approach for their measurement involves laborious liquid-liquid extraction followed by high-performance liquid chromatography (HPLC) analysis on dedicated instrumentation. We describe a simple, rapid protocol for measurement of vitamin A and E and their integration into an existing online sample preparation liquid chromatography tandem mass spectrometry (SPLC-MS/MS) workflow. METHODS: We performed a method comparison between the SPLC-MS/MS and HPLC methods for vitamin A and E by measuring patient specimens across the concentration range 11-81 µg/dL for vitamin A and 1-18 mg/L for vitamin E. The analysis times on each platform were also compared. RESULTS: SPLC-MS/MS and HPLC methods were comparable with regards to analytical performance; mean bias across the measured range was 2.54% (95% CL: -11.56-16.64%) for vitamin A and -2.04% (95% CL: -18.20-14.12%) for vitamin E. Total analysis times were 7 min and 15 min for SPLC-MS/MS and HPLC respectively. CONCLUSIONS: The development of a simplified sample preparation protocol and the use of multiplexing SPLC-MS/MS have reduced sample analysis times for vitamin A and E. This method has also optimized clinical workflow through consolidation of previously independent benches.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Vitamina A/sangue , Vitamina E/sangue , 25-Hidroxivitamina D 2/análise , Anticonvulsivantes/análise , Bussulfano/análise , Humanos , Imunossupressores/análise , Laboratórios/organização & administração , Padrões de Referência , Reprodutibilidade dos Testes , Fluxo de Trabalho
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