Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
1.
Comput Biol Med ; 164: 107363, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37595520

RESUMO

Gold nanoparticles (Au-NPs) have been used for a long time to target cancer cells. Different modalities have been suggested to utilize Au-NPs in cancer patients. We construct both normal and cancer cell membranes to simulate the Au-NP entry to understand better how it can penetrate the cancer cell membrane. We use molecular dynamics simulation (MDS) on both normal and cancer cell membrane models for 150 ns. At the same time, we prepared the Au-NP of spherical shape (16 nm radius) capped with citrate using MDS for 100 ns. Finally, we added the Au-NP close to the membranes and moved it using 1000 kJ mol-1 nm-1 force constant during the 7.7 ns MDS run. We analyzed the membranes in the presence and absence of the Au-NP and compared normal and cancer membranes. The results show that normal cell membranes have higher stability than cancer membranes. Additionally, Au-NP forms pore in the membranes that facilitate water and ions entry during the movement inside the lipid bilayer region. These pores are responsible for the enhanced response of Au-NP-loaded chemotherapeutic agents in cancer treatment.


Assuntos
Nanopartículas Metálicas , Neoplasias , Humanos , Ouro , Membrana Celular , Simulação de Dinâmica Molecular
2.
Heliyon ; 9(4): e15078, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37089392

RESUMO

Toxic element accumulation in the surrounding soils of the advanced industry- and agriculture-oriented areas may lead to severe environmental degradation and harmful impact on inhabitants. This work examined the concentration of some concerned toxic elements (Cr, Pb, Cd, Cu, As, and Ni) in the representative topsoil from 10 industrially contaminated sites in central Bangladesh (Narayanganj district) using an Inductively Coupled Plasma Mass Spectrometer concerning the probable ecological and human health risks. The mean concentrations (mg/kg) of the elements were found in the order of Ni (58.1 ± 11.8) > Pb (34.1 ± 14.3) > Cr (32.1 ± 6.77) > Cu (14.5 ± 3.30) > Cd (2.74 ± 1.08) > As (1.49 ± 0.43). The findings pointed out that diversified manmade events enhanced the intensities of elemental contamination through the studied sites. Source analysis showed that Cr, Pb, As, and Cd may originate from industrial wastewater and agricultural activities, whereas Cu and Ni came from natural sources. The geo-accumulation index level for Cd (1.70-3.39) was determined as grade 3 (moderately to strongly polluted), the enrichment factor score for Cd (13.9) fell in the very severe enhanced category (cluster 5), and the highest contamination factor value was found for Cd (15.7). The contamination degree values for all the tested elements signify a moderate to severe contamination grade; conversely, pollution load index levels depicted the nonexistence of elemental pollution. The assessment revealed serious Cd pollution in agricultural soils and moderate to significant potential ecological risk for the rest of the examined toxic elements. Furthermore, hazard index values exceeded the safe exposure levels, indicating that there was potential non-carcinogenic risk in the soils for children and adults. Ingestion exposure had much higher carcinogenic risk values than inhalation and cutaneous exposure, and children are exposed to considerable carcinogenic hazards. Therefore, it is suggested that the harmful practices that expose this farming soil to contaminants should be stopped immediately and effective environment-friendly techniques of waste management and effluent treatment should be employed in the study area.

3.
Clin Ophthalmol ; 16: 2699-2703, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017507

RESUMO

Purpose: To evaluate the role of automated peripheral iridectomy as an adjunctive tool combined with phacoemulsification and ExPRESS shunt implantation in management of cases with chronic angle closure glaucoma. Setting: Magrabi eye hospital. Methods: This prospective study included 22 eyes of 22 patients with chronic angle closure glaucoma and cataract who underwent Ex-PRESS shunt implantation, cataract extraction and surgical peripheral iridectomy at the site of shunt implantation in the period between January 2018 and April 2020. Results: After surgery, the mean IOP was 11.3±1.2 mm Hg, 14.5±1.6 mm Hg, 14.8±2.1 mm Hg, 15.3±1.9 mm Hg and 17.4±1.8 mm Hg at 7 days, 1 month, 3 months, 6 months and 12 months, respectively. All postoperative IOP was significantly lower compared with preoperative IOP (P = 0.001). There was a significant decrease in the number of medications required after surgery. The baseline mean number of medications was 3.4±0.02 (range from 1 to 4), while postoperatively the mean number of medications decreased to 0.7±0.01 at 12 months (P < 0.01). The qualified success rate was 6/22 eyes, and the complete success rate was 16/22 (72.7%) at 12 months, respectively. Conclusion: The combined phacoemulsification and Ex-PRESS shunt implantation with automated peripheral iridectomy is an effective and safe procedure to treat chronic angle closure glaucoma.

4.
J Photochem Photobiol B ; 234: 112540, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35973287

RESUMO

The unusual physical, chemical, and biological features of nanoparticles have sparked considerable attention in the ophthalmological applications. This study reports the synthesis and characterization of zinc oxide nanoparticles (ZnONPs) using laser-ablation at 100 mJ with different ablation times. The synthesized ZnONPs were spherical with an average size of 10.2 nm or 9.8 nm for laser ablation times of 20 and 30 min, respectively. The ZnONPs were screened for their antimicrobial activity against ophthalmological bacteria, methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa. The significant decrease in bacterial growth was observed after treatment with ZnONPs in combination with 400 nm femtosecond laser irradiation. ZnONPs were investigated for their antioxidant activity and biocompatibility towards retinal epithelial cells (ARPE-19). ZnONPs showed moderate antioxidant and free radical scavenging activity. ZnONPs prepared with an ablation time of 20 min were safer and more biocompatible than those prepared with an ablation time of 30 min, which were toxic to ARPE-19 cells with LC50 (11.3 µg/mL) and LC90 (18.3 µg/mL). In this study, laser ablation technique was used to create ZnONPs, and it was proposed that ZnONPs could have laser-activated antimicrobial activity for ophthalmological applications.


Assuntos
Anti-Infecciosos , Terapia a Laser , Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Óxido de Zinco , Anti-Infecciosos/farmacologia , Antioxidantes , Células Epiteliais , Lasers , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Nanopartículas/química , Óxido de Zinco/química
5.
Rev. CES psicol ; 15(1): 182-200, ene.-abr. 2022. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1376235

RESUMO

Resumen Este artículo presenta una reflexión sobre la autoridad docente en el contexto de la cultura actual, marcada por los discursos del capitalismo y de la ciencia, de los cuales surge una nueva subjetividad. El objetivo de este trabajo es discurrir sobre la incidencia de los discursos del capitalismo y de la ciencia en la declinación de la autoridad docente. En un primer momento, se aborda el proyecto y la subjetividad moderna fundados en los productos de la razón; posteriormente, se indica cómo dicho proyecto entra en una fase de sospecha, por sus efectos en el siglo XX y por la crítica realizada por los maestros de la sospecha. Luego se desarrolla la declinación de la función del padre por la incidencia del discurso del capitalismo, continuando con las consecuencias subjetivas de la declinación de la autoridad docente que genera una nueva subjetividad basada en los derechos individuales hedonistas, para finalizar con la declinación de la autoridad docente, entendida desde dos perspectivas: empresarial y epistémica, que tienen por consecuencia la forclusión de la singularidad. Se concluye que el lugar de la autoridad docente es afectado por dos elementos: primero, por el discurso del capitalismo en su relación con el discurso de la ciencia porque borra la disimetría del lazo social, donde el vínculo docente-estudiante se torna simétrico marcado por el valor de laigualdad; y segundo, por el empuje al Uno de la estandarización del conocimiento dado por políticas educativas internacionales en las que el docente es un instrumento.


Abstract This article reflects on the teaching authority in the context of current culture, marked by the discourses of capitalism and science, from which a new subjectivity emerges from these discourses. The objective to be developed is the incidence of the discourses of capitalism and science in the decline of teaching authority. At first, the project and the modern subjectivity based on the products of reason are approached, later it is indicated how this project is under an initial phase of suspicion, due to its effects in the 20th century and the criticism exerted by the masters of the suspicion. To end with the decline of the teaching authority, understood from two perspectives: business and epistemic that result in the foreclosure of the singularity. It is concluded that the place of teaching authority is affected by two elements: first, by the discourse of capitalism in its relationship with the discourse of science because it erases the dissymmetry of the social bond, where teacher-student bond becomes symmetrical marked by the value of equality; and second, by the push to One of the standardization of knowledge given by international educational policies in which the teacher is an instrument.

6.
Toxicol Res (Camb) ; 11(1): 22-31, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35237408

RESUMO

Natural antioxidant products play a vital role in the treatment and prevention of cancer disease because they have no side effects. This study aimed to compare the chemoprotective effect of Spirulina platensis (SP) and garlic against hepatocellular carcinoma (HCC) in rats. This study was being done by using 60 male Wistar rats and divided into four groups. Group (I): normal group. Group (II): HCC group induced by injection of a single dose of DEN (200 mg/kg/I.P) and after 14 days injected CCl4 (1 mg/kg/I.P) 3 times/week/six weeks. Group (III): HCC group received SP orally at a dose (500 mg/kg). Group (IV): HCC group received garlic (250 mg/kg) orally. The results revealed that the Spirulina and garlic treatment have a significant decrease in Glutamate pyruvate transaminase, Glutamate oxaloacetate transaminase, GGT, LDH, and the Malondialdehyde (MDA) activity, and furthermore, a significant increase in the total protein level, the superoxide dismutase (SOD), and Catalase (CAT) activity nearly to normal activity. Furthermore, the hepatic expression of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase, transforming growth factor-beta (TGF-ß1), Heat Shock Protein glycoprotein 96 (HSPgp96), and Glypican 3 (GP3) were down regulated by the Spirulina and garlic treatment in comparison with those in HCC group. All findings reported that the chemoprotective of both Spirulina and garlic that have nearly the same effect may be due to antioxidant activity and inhibition of lipid peroxidation, amelioration of pro-inflammatory cytokine, HSPgp96, and GP3.

8.
Biol Trace Elem Res ; 200(1): 197-205, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33559025

RESUMO

The widespread industrial use of nitrite in preservatives, colorants, and manufacturing rubber products and dyes increases the possibilities of organ toxicity. Lithium borate (LB) is known as an antioxidant and an oxidative stress reliever. Therefore, this study is aimed at examining the effect of LB on nitrite-induced hepatorenal dysfunction. Twenty-eight male Swiss mice were divided into four equal groups. Group 1, the control group, received saline. Group 2 received LB orally for 5 consecutive days at a dose of 15 mg/kg bw. Group 3, the nitrite group, received sodium nitrite (NaNO2) on Day 5 (60 mg/kg bw intraperitoneally). Group 4, the protective group (LB + NaNO2 group), received LB for 5 days and then a single dose of NaNO2 intraperitoneally on Day 5, the same as in Groups 2 and 3, respectively. Samples of blood and kidney were taken for serum analysis of hepatorenal biomarkers, levels of antioxidants and cytokines, and the expression of genes associated with oxidative stress and inflammation. NaNO2 intoxication increased markers of liver and kidney functions yet decreased reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities in blood. NaNO2 also increased the expression of tumor necrosis factor (TNF-α), interleukin-1ß and interleukin-6 (IL-1ß and IL-6). Pre-administration of LB protected mice from oxidative stress, lipid peroxidation, and the decrease in antioxidant enzyme activity. Moreover, LB protected mice from cytokine changes, which remained within normal levels. LB ameliorated the changes induced by NaNO2 on the mRNA of nuclear factor erythroid 2-related factor 2 (Nfr2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), transforming growth factor-beta 2 (TGF-ß2), and glutathione-S-transferase (GST) as determined using quantitative real-time PCR (qRT-PCR). These results collectively demonstrate that LB ameliorated NaNO2-induced oxidative stress by controlling the oxidative stress biomarkers and the oxidant/antioxidant state through the involvement of the Nrf2/HO-1 and NF-κB signaling pathways.


Assuntos
Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Animais , Antioxidantes/farmacologia , Boratos/farmacologia , Heme Oxigenase-1/metabolismo , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Oxidantes , Estresse Oxidativo , Nitrito de Sódio/toxicidade
9.
Artigo em Inglês | MEDLINE | ID: mdl-34574650

RESUMO

Liver disease, especially liver cancer, has become a threat facing the world. Now, antioxidant products are garnering great attention for the treatment and prevention of many diseases. S-Methyl methionine sulfonium chloride (MMSC) is a methionine derivative and is present in many vegetables and has anti-inflammatory effects and antioxidants. This is the first study aiming to investigate the antitumor activity of the MMSC. This study was carried out on 60 male Wistar albino rats (4-6 weeks old age) and divided into four groups, with the first group as normal control, second group as hepatocarcinoma induced by diethyl nitrosamine and carbon tetrachloride (DEN/CCL4) group, third group as normal rats treated with MMSC, and fourth group as hepatocellular carcinoma (HCC) induced rats treated with MMSC. Our findings revealed that MMSC administration after HCC induction significantly improved (p < 0.05) the liver function biomarkers, including AST, GGT, albumin, globulin, and albumin/globulin ratio (A/G), in comparison with those in the HCC group. Moreover, the histopathological changes of the liver tissue in the HCC group were improved by MMSC treatment. Likewise, the expression levels of tumor necrosis factor-alpha (TNF-α), induced nitric oxide synthase (iNOS), transforming growth factor (TGF-1ß), and glypican 3 (GP3) were downregulated by MMSC treatment after HCC induction in comparison with those in the HCC-induced group. In conclusion, MMSC showed antitumor activity against HCC induction by DEN/CCl4 through decreasing lipid peroxide formation, the expression level of an inflammatory cytokines such as (TNF-α), immunoregulatory cytokines such as (TGF-1ß), induced nitric oxide synthase, and glypican 3.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Vitamina U , Animais , Antioxidantes , Carbono , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/tratamento farmacológico , Cloretos , Dietilnitrosamina/toxicidade , Fígado , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Metionina/análogos & derivados , Ratos , Ratos Wistar
10.
J Refract Surg ; 37(8): 510-515, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34388076

RESUMO

PURPOSE: To evaluate the effects of femtosecond laser small incision lenticule extraction (SMILE) on treating unilateral myopic anisometropia in children with spectacles or contact lens intolerance. METHODS: This was a retrospective study that included children with unilateral myopic anisometropic amblyopia who underwent a SMILE procedure at Alpha Vision Center, Zagazig, Egypt, from January 2014 to December 2016. RESULTS: One hundred twenty-four eyes of 124 patients were included in this study. The postoperative corrected distance visual acuity (CDVA) at the 3-month and 1-, 2-, 3-, and 4-year follow-up visits improved significantly (P < .05) compared to the preoperative CDVA, indicating the safety of the procedure. At the 3-month postoperative visit, 23% of cases showed improvement of one or more lines of CDVA, whereas only 2% of cases showed a decline of only one line. Moreover, the postoperative uncorrected distance visual acuity compared favorably to the preoperative CDVA, denoting the efficacy of the refractive correction. The spherical equivalent was within ±0.50 diopters of the intended correction in 75% of the cases and within ±1.00 diopters in 89% of the cases. The intraoperative complications were scarce and relatively innocuous. CONCLUSIONS: SMILE is a safe and effective alternative method for correcting myopic anisometropic amblyopia in children with spectacles or contact lens intolerance with good refractive results. A larger study with longer follow-up periods is necessary to determine the long-term effects of SMILE. [J Refract Surg. 2021;37(8):510-515.].


Assuntos
Anisometropia , Miopia , Anisometropia/cirurgia , Criança , Substância Própria/cirurgia , Seguimentos , Humanos , Lasers de Excimer/uso terapêutico , Miopia/cirurgia , Refração Ocular , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual
11.
Int. j. morphol ; 39(2): 407-415, abr. 2021. ilus, graf
Artigo em Inglês | LILACS | ID: biblio-1385337

RESUMO

SUMMARY: Amiodarone (AMD), an orally powerful antidysrhythmic medication that has caused hepatotoxicity on long-term administration, is commonly used across the world. Silymarin ameliorative effects (SLM); this research elucidated the magnitude of the damage to the liver tissue in AMD. We divided 24 albino rats evenly into four groups given daily doses by gastric tube for eight weeks as follows; the 1st group acted as a control group; the 2nd group received SLM; the 3rd group received AMD; and the 4th group received AMD parallel to SLM. Liver tissues prepared for light, electron microscopic and serum samples screened for biomarkers (I)liver injury enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); (II) oxidative and antioxidant stress, malondialdehyde (MDA) and superoxide dismutase (SOD); and (III) inflammatory markers, tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6). The findings showed that AMD caused hepatic histological changes that included congestion of the blood vessels, leucocytic infiltration and cytoplasmic vacuolation. Ultrastructural degeneration of the mitochondria, endoplasmic reticulum swelling, nuclear pyknosis and increased fat droplets and lysosomes were observed. The biochemical findings showed an increase in the AMD group's ALT and AST activities. The group of rats treated with AMD and SLM, increased the improvements in histology and ultrastructure, while the ALT and AST levels were reduced. Our findings collectively agreed that SLM has a protective impact on AMD hepatotoxicity which can be due to its antioxidant properties.


RESUMEN: La amiodarona (AMD) es un fuerte medicamento antiarrítmico administrado por vía oral que ha causado hepatotoxicidad en la administración a largo plazo utilizado con frecuencia en todo el mundo. Efectos de mejora de la silimarina (SLM); esta investigación analizó la magnitud del daño al tejido hepático en la DMAE. Dividimos 24 ratas albinas de manera uniforme en cuatro grupos que recibieron dosis diarias por sonda gástrica durante ocho semanas de la siguiente manera; el primer grupo fue designado como grupo control; el segundo grupo recibió SLM; el tercer grupo recibió AMD; y el cuarto grupo recibió AMD en paralelo a SLM. Se prepararon tejidos hepáticos para muestras de suero, microscopía de luz y electrónica y se analizaron para biomarcadores (I) enzimas de daño hepático, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST); (II) estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (III) marcadores inflamatorios, factor de necrosis tumoral alfa (TNF-a) e interleucina-6 (IL-6). Los hallazgos mostraron que la DMAE genera cambios histológicos hepáticos que incluyen congestión de los vasos sanguíneos, infiltración leucocítica y vacuolación citoplásmica. Se observó una degeneración ultraestructural de las mitocondrias, aumento del retículo endoplásmico, picnosis nuclear y aumento de gotitas de grasa y lisosomas. Los hallazgos bioquímicos mostraron un aumento en las actividades de ALT y AST del grupo AMD. El grupo de ratas tratadas con AMD y SLM, aumentó las mejoras en histología y ultraestructura, mientras que se redujeron los niveles de ALT y AST. Nuestros hallazgos coincidieron colectivamente en que SLM tiene un impacto protector sobre la hepatotoxicidad de AMD debido a sus propiedades antioxidantes.


Assuntos
Animais , Feminino , Ratos , Silimarina/administração & dosagem , Substâncias Protetoras/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Amiodarona/toxicidade , Fígado/efeitos dos fármacos , Aspartato Aminotransferases/análise , Ratos Endogâmicos , Silimarina/farmacologia , Superóxido Dismutase , Microscopia Eletrônica , Interleucina-6 , Fator de Necrose Tumoral alfa , Estresse Oxidativo , Substâncias Protetoras/farmacologia , Alanina Transaminase/análise , Fígado/enzimologia , Fígado/ultraestrutura , Malondialdeído , Antiarrítmicos/toxicidade
12.
Cardiovasc Drugs Ther ; 35(6): 1095-1110, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-32474680

RESUMO

PURPOSE: This study tested if the protective anti-remodeling effect of GLP-1 agonist Exendin-4 after an acute myocardial infarction (MI) in rats involves inhibition of the Wnt1/ß-catenin signaling pathway. METHODS: Rats were divided into sham, sham + Exendin-4 (10 µg/day, i.p), MI, and MI + Exendin-4. MI was introduced to rats by permanent left anterior descending coronary artery (LAD) ligation. RESULTS: On day 7 post-infraction, MI rats showed LV dysfunction with higher serum levels of cardiac markers. Their remote myocardia showed increased mRNA and protein levels of collagen I/III with higher levels of reactive oxygen species (ROS) and inflammatory cytokines, as well as protein levels of Wnt1, phospho-Akt, transforming growth factor (TGF-ß1), Smad, phospho-Smad3, α-SMA, caspase-3, and Bax. They also showed higher protein levels of phospho-glycogen synthase kinase-3ß (p-GSK3ß), as well as total, phosphorylated, and nuclear ß-catenin with a concomitant decrease in the levels of cyclic adenosine monophosphate (cAMP), mRNA of manganese superoxide dismutase (MnSOD), and protein levels of Bcl-2, ß-arrestin-2, and protein phosphatase-2 (PP2A). Administration of Exendin-4 to MI rats reduced the infarct size and reversed the aforementioned signaling molecules without altering protein levels of TGF-1ß and Wnt1 or Akt activation. Interestingly, Exendin-4 increased mRNA levels of MnSOD, protein levels of ß-arrestin-2 and PP2A, and ß-catenin phosphorylation but reduced the phosphorylation of GSK3ß and Smad3, and total ß-catenin levels in the LV of control rats. CONCLUSION: Exendin-4 inhibits the remodeling in the remote myocardium of rats following acute MI by attenuating ß-catenin activation and activating ß-arrestin-2, PP2A, and GSK3ß. Graphical Abstract A graphical abstract that illustrates the mechanisms by which Exendin-4 inhibits cardiac remodeling in remote myocardium of left ventricle MI-induced rats. Mechanisms are assumed to occur in the cardiomyocytes and/or other resident cells such as fibroblast. Β-catenin activation and nuclear translocation are associated with increased synthesis of inflammatory cytokines and transforming growth factor ß-1 (TGF-ß1). GSK3ß is inhibited by phosphorylation at Ser9. Under normal conditions, ß-catenin is degraded in the cytoplasm by the active GSK3ß-dependent degradation complex (un-phosphorylated) which usually phosphorylates ß-catenin at Ser33/37/Thr41. After MI, TGF-ß1, and Wnt 1 levels are significantly increased, the overproduction of Wnt1 induces ß-catenin stabilization and nuclear translocation through increasing the phosphorylation of disheveled (DVL) protein which in turn phosphorylates and inhibits GSK3ß. TGF-ß1 stimulates the phosphorylation of Smad-3 and subsequent nuclear translocation to activate the transcription of collage 1/III and α-smooth muscle actin (α-SMA). Besides, TGF-ß1 stabilizes cytoplasmic ß-catenin levels indirectly by phosphorylation of Akt at Thr308-induced inhibition of GSK3ß by increasing phosphorylation of Ser9. Exendin-4, and possibly through G protein-coupled receptors (GPCRs), increases levels of cAMP and upregulates ß-arrestin-2 levels. Both can result in a positive inotropic effect. Besides, ß-arrestin-2 can stimulate PP2A to dephosphorylation Smad3 (inhibition) and GSK3ß (activation), thus reduces fibrosis and prevents the activation of ß-catenin and collagen deposition.


Assuntos
Exenatida/farmacologia , Quinase 3 da Glicogênio Sintase/efeitos dos fármacos , Infarto do Miocárdio/fisiopatologia , Proteína Fosfatase 2/efeitos dos fármacos , beta Catenina/efeitos dos fármacos , beta-Arrestinas/efeitos dos fármacos , Animais , Hemodinâmica/efeitos dos fármacos , Masculino , Fosforilação , Ratos , Ratos Wistar , Proteína Wnt1/efeitos dos fármacos
13.
J Cardiovasc Transl Res ; 14(4): 619-635, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32239434

RESUMO

This study evaluated if the cardioprotective effect of Exendin-4 against ischemia/reperfusion (I/R) injury in male rats involves modulation of AMPK and sirtuins. Adult male rats were divided into sham, sham + Exendin-4, I/R, I/R + Exendin-4, and I/R + Exendin-4 + EX-527, a sirt1 inhibitor. Exendin-4 reduced infarct size and preserved the function and structure of the left ventricles (LV) of I/R rats. It also inhibited oxidative stress and apoptosis and upregulated MnSOD and Bcl-2 in their infarcted myocardium. With no effect on SIRTs 2/6/7, Exendin-4 activated and upregulated mRNA and protein levels of SIRT1, increased levels of SIRT3 protein, activated AMPK, and reduced the acetylation of p53 and PGC-1α as well as the phosphorylation of FOXO-1. EX-527 completely abolished all beneficial effects of Exendin-4 in I/R-induced rats. In conclusion, Exendin-4 cardioprotective effect against I/R involves activation of SIRT1 and SIRT3. Graphical Abstract Exendin-4 could scavenge free radical directly, upregulate p53, and through upregulation of SIRT1 and stimulating SIRT1 nuclear accumulation. In addition, Exendin-4 also upregulates SIRT3 which plays an essential role in the upregulation of antioxidants, inhibition of reactive oxygen species (ROS) generation, and prevention of mitochondria damage. Accordingly, SIRT1 induces the deacetylation of PGC-1α and p53 and is able to bind p-FOXO-1. This results in inhibition of cardiomyocyte apoptosis through increasing Bcl-2 levels, activity, and levels of MnSOD; decreasing expression of Bax; decreasing cytochrome C release; and improving mitochondria biogenesis through upregulation of Mfn-2.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Exenatida/farmacologia , Incretinas/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Sirtuína 1/metabolismo , Sirtuínas/metabolismo , Acetilação , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Ativação Enzimática , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fosforilação , Ratos Wistar , Transdução de Sinais , Sirtuína 1/genética , Sirtuínas/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima , Função Ventricular Esquerda/efeitos dos fármacos
14.
Toxicol Res (Camb) ; 10(6): 1092-1103, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34992771

RESUMO

Hepatocellular carcinoma (HCC) is a serious threat to human health that has attracted substantial interest. The purpose of this study was to investigate the modulatory effect of bee honey against induced HCC by diethylnitrosamine/carbon tetrachloride (DEN/CCl4) in rats. HCC was induced by a single intraperitoneal dose of DEN (200 mg/kg B.W). Two weeks later, CCl4 (1 ml/kg) was intraperitoneally injected (three times a week). Bee honey was administered orally at 2 g/rat before and after the induction of HCC. The results showed that bee honey administration significantly increased body weight, decreased liver weight, and relative liver weight compared to those in the HCC-induced group. Moreover, a significant decrease in serum alpha-fetoprotein (AFP) as well as AST, ALT, GGT, ALP activities were observed in bee honey administration rats compared with those in HCC-induced group. Also, the hepatic MDA was significantly decreased; in addition, SOD, CAT, and GPx activities were significantly increased in groups treated with bee honey compared with those in the HCC group. The hepatic histopathology alterations caused by DEN/CCl4 injection were ameliorated by bee honey treatment. Likewise, the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor (TGF-ß1), intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), glypican (GP-3), thioredoxin (TRX), and glutaredoxin (GRX) were downregulated, and caspase-3 was upregulated by bee honey treatment compared with untreated HCC-induced group. In conclusion, bee honey has remarkable beneficial effects against HCC induced in rats through its antioxidant, anti-inflammatory, antifibrotic, and antimetastatic effects. PRACTICAL APPLICATIONS: The current study confirmed that honey has the potential to act as an antimetastatic factor. Bee honey supplementation either before or after combined injection of DEN/CCl4 exhibited inhibitory and ameliorative effects against DEN/CCl4-induced HCC through its antioxidant, antiproliferative, anti-metastatic, antifibrotic, and apoptosis properties. To our knowledge, this is the first study to describe the molecular mechanisms underlying honey's effects against DEN/CCl4-induced HCC in rats.

15.
Int. j. morphol ; 38(6): 1786-1796, Dec. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1134512

RESUMO

SUMMARY: Bisphenol A (BPA) is an industrial chemical widely used to make polycarbonate plastics for packaging and epoxy resins. This study sought to examine how selenium (Se) affects BPA toxicity in terms of albino rats' histological structure, antioxidant enzymes and reproductive organs (seminiferous tubules). Twenty-four adult male rats were divided into four experimental groups: Group 1: Control; Group 2: Orally administered BPA; Group 3: Orally administered sodium selenite; Group 4: Treated daily with BPA followed by selenium (Se). All experiment done for 4 weeks. BPA exposure caused changes in the testicular histological structure, which consists apoptosis, and led to changes in several biochemical markers: Malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase. However, these BPA side effects may be ameliorated in rats treated with BPA-plus-Se. These protective effects of Se may attributable to its ability to remove potentially damaging oxidizing agents in living organisms. The results may confirm that Se countered the oxidant effects and increased the BPA-induced stress response in rats. So, Se promotes the healthy growth and development of mammals by protecting them from oxidative stress. As human are greatly exposed to BPA and it can accumulate in tissues, there is concern about human reproductive functions particularly for occupational workers exposed usually to greater levels of BPA. Thus, the use of BPA in multiple industries must be restricted and the inaccurate usage of plastic containers should be avoided to decrease the health hazards. Administration of Se may protect against the adverse effects of BPA on reproductive functions and structures.


RESUMEN: El bisfenol A (BPA) es un químico industrial ampliamente utilizado para fabricar plásticos de policarbonato para envases y resinas epoxi. Este estudio examinó el efecto de selenio (Se) en la toxicidad del BPA en términos de la estructura histológica, enzimas antioxidantes y los órganos reproductivos (túbulos seminíferos) de ratas albinas. Se dividieron veinticuatro ratas macho adultas en cuatro grupos experimentales: Grupo 1: control; Grupo 2: BPA administrado por vía oral; Grupo 3: BPA administrado por vía oral para; Grupo 4: tratado diariamente con BPA seguido de selenio (Se). El experimento se realizó durante cuatro semanas y se observó que la exposición al BPA provocó cambios en la estructura histológica testicular, incluyendo apoptosis, y alteraciones en varios marcadores bioquímicos:malondialdehído, catalasa, superóxido dismutasa y glutatión peroxidasa. Sin embargo, estos efectos secundarios del BPA pueden mejorar en ratas tratadas con BPA-plus-Se. Estos efectos protectores del Se pueden ser atribuidos a la capacidad de eliminar agentes oxidantes potencialmente dañinos en organismos vivos. Los resultados indicaron que se contrarrestaron los efectos oxidantes y aumentó la respuesta al estrés inducido por BPA en ratas, y favorece el crecimiento y desarrollo en los mamíferos al protegerlos del estrés oxidativo. Debido a la exposición al BPA en el ser humano, se puede acumular en los tejidos, por lo que existe una preocupación por el daño a las funciones reproductivas en particular de los trabajadores que generalmente están expuestos a niveles más altos de BPA. Por lo tanto, se debe restringir el uso de BPA en las industrias y evitar el uso incorrecto de envases de plástico para así disminuir los riesgos para la salud. La administración correcta de Se puede proteger contra los efectos adversos del BPA en las funciones y estructuras reproductivas.


Assuntos
Animais , Masculino , Ratos , Fenóis/toxicidade , Selênio/farmacologia , Testículo/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Antioxidantes/farmacologia , Fenóis/administração & dosagem , Superóxido Dismutase/efeitos dos fármacos , Testículo/patologia , Compostos Benzidrílicos/administração & dosagem , Microscopia Eletrônica , Biomarcadores , Catalase/efeitos dos fármacos , Administração Oral , Apoptose/efeitos dos fármacos , Estresse Oxidativo , Glutationa Peroxidase/efeitos dos fármacos
16.
Clin Ophthalmol ; 14: 1055-1058, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368003

RESUMO

PURPOSE: To describe a new technique for transconjunctival intrascleral fixation of Cionni CTR using double-flanged polypropylens suture. METHODS: This is a prospective interventional case series which included 7 cases with severe (more than 180 degrees) zonular dialysis. Three cases were hereditary lens subluxation (Marfan syndrome), 2 cases with traumatic subluxation and 2 cases with pseudo-exfoliation syndrome. RESULTS: All cases achieved a good postoperative stable and centered IOL with good visual results. No postoperative complications were recorded apart from PCO in 3 cases and mild bleeding during needle passage in one case. CONCLUSION: This described technique is a simple, time sparing and minimally invasive method for achieving good bag centration. It eliminates the need of conjunctival peritomy, subconjunctival vessels cautery and scleral fashioning of a flap, pocket or a groove. The use of 6/0 polypropylene theoretically can achieve better longevity.

17.
Gulf J Oncolog ; 1(32): 71-87, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32342923

RESUMO

With cancer being the third leading cause of mortality in the United Arab Emirates (UAE), there has been significant investment from the government and private health care providers to enhance the quality of cancer care in the UAE. The UAE is a developing country with solid economic resources that can be utilized to improve cancer care across the country. There is limited data regarding the incidence, survival, and potential risk factors for cancer in the UAE. The UAE Oncology Task Force was established in 2019 by cancer care providers from across the UAE under the auspices of Emirates Oncology Society. In this paper we summarize the history of cancer care in the UAE, report the national cancer incidence, and outline current challenges and opportunities to enhance and standardize cancer care. We provide recommendations for policymakers and the UAE Oncology community for the delivery of high-quality cancer care. These recommendations are aligned with the UAE government's vision to reduce cancer mortality and provide high quality healthcare for its citizens.


Assuntos
Neoplasias/epidemiologia , História do Século XXI , Humanos , Emirados Árabes Unidos
18.
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
19.
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 , Injúria 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
20.
Int. j. morphol ; 38(1): 48-55, Feb. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1056396

RESUMO

This research was designed to investigate the potential protective effect of vitamin C supplementation against hepatocyte ultrastructural alterations induced by artemether (antimalarial drug) administration. Twenty-four adult male albino rats were used in this study and were divided into four groups (n=6). Group I served as a control and rats in group II administrated artemether (4 mg/kg B.W) orally for three consecutive days. Group III administered artemether plus a low dose of vitamin C (2.86 mg/kg/l water) while group IV received artemether plusa high dose of vitamin C (8.56 mg/kg). At the end of the experimental period (14 days), the harvested liver tissues were examined by transmission electron microscopy (TEM), and blood samples were assayed for biomarkers of liver injury and oxidative stress. Artemether significantly (p<0.05) augmented biomarkers of liver injury such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and oxidative stress such as superoxide dismutase (SOD), Glutathione Peroxidase (GPX), and caused degeneration and damage of the rough endoplasmic reticulum and disrupted mitochondria. The blood sinusoids were also damaged with distortion of their canaliculi. Administration of vitamin C showed improvement of liver biomarkers, and liver parenchyma, especially in a high dose of vitamin C.We concludes that vitamin C is a partial protective agent against artemether-induced liver injury.


Esta investigación fue diseñada para investigar el posible efecto protector de la vitamina C contra las alteraciones ultraestructurales de los hepatocitos, inducidas por la administración de arteméter (medicamento antipalúdico). En el estudio se utilizaron 24 ratas albinas macho adultas y se dividieron en cuatro grupos (n = 6). El grupo I fue designado como control y las ratas en el grupo II se adminstró Arteméter (4 mg / kg de peso corporal) por vía oral durante tres días consecutivos. En el grupo III se administró arteméter, además de una dosis baja de vitamina C (2,86 mg / kg / l de agua) mientras que el grupo IV recibió arteméter más una dosis alta de vitamina C (8,56 mg / kg). Al final del período experimental (14 días), los tejidos hepáticos recolectados se examinaron por microscopía electrónica de transmisión (MET), y las muestras de sangre se analizaron en busca de biomarcadores de daño hepático y estrés oxidativo. El arteméter aumentó significativamente (p <0,05) los biomarcadores de daño hepático como alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) y estrés oxidativo como superóxido dismutasa (SOD), glutatión peroxidasa (GPX) y causó degeneración y daño de la retículo endoplásmico rugoso y mitocondrias alteradas. Los sinusoides sanguíneos también fueron dañados con la distorsión de sus canalículos. La administración de vitamina C mostró una mejoría de los biomarcadores hepáticos y el parénquima hepático, especialmente en una dosis alta de vitamina C. Concluimos que la vitamina C es un agente protector parcial contra la lesión hepática inducida por arteméter.


Assuntos
Animais , Ratos , Ácido Ascórbico/administração & dosagem , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Artemeter/toxicidade , Ácido Ascórbico/farmacologia , Superóxido Dismutase/análise , Biomarcadores , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/ultraestrutura , Microscopia Eletrônica de Transmissão , Modelos Animais de Doenças , Medicamentos Hepatoprotetores , Doença Hepática Induzida por Substâncias e Drogas/patologia , Glutationa Peroxidase/análise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA