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1.
Environ Technol ; 44(22): 3466-3478, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35410576

RESUMO

This work is interested in studying the removal of 27 harmful pollutants from drinking water in the Rosetta branch of the River Nile by advanced treatment processes (i.e. photo-catalysis under natural conditions and normal pH of surface water). The concentration levels of the selected pesticides (11 compounds) in raw water by the spiking method ranged from 1.57-0.40 µg/L, while the concentration of pharmaceuticals (10 compounds) ranged from 41.56-5.95 µg/L and the herbicides (6 compounds) in the range of 1.89-1.37 µg/L. For this purpose, TiO2-Hombikat/alumina (T/A) was prepared by a two-step method; sonication followed by the hydrothermal method. Cu/TiO2-Hombikat/alumina was prepared hydrothermally (H-Cu/T/Al) and by the wet impregnation method (Ma-Cu/T/Al). The prepared materials were characterized by XRD and SEM. The use of advanced treatment could successfully remove selected pollutants. In the case of pharmaceutical residues, the prepared catalysts showed a powerful efficiency in the complete removal of sulfamethazine, while only (T/A) and (H-Cu/T/Al) showed such an efficiency in the complete removal of diclofenac sodium. On the other hand, lower efficiencies were observed with caffeine (17.99% (T/A) and 24.05% (H-Cu/T/Al)). In the case of pesticides, a high removal of pendimethalin (93.77%) using (H-Cu/T/Al) and 86.03% by using (Mb-Cu/T/Al), whereas lower efficiencies were observed for T/A toward the degradation of aldicarb (15.6%) (l) and H-Cu/T/Al (26.07%). In the case of herbicides, the catalysts showed no more than 57% efficiency in the removal of these pollutants.


Assuntos
Água Potável , Herbicidas , Praguicidas , Poluentes Químicos da Água , Herbicidas/química , Praguicidas/química , Preparações Farmacêuticas , Poluentes Químicos da Água/química , Catálise
2.
Sci Rep ; 12(1): 17009, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36220849

RESUMO

The aim of this study is to describe the performance of the aluminum oxide nanoparticle and metal aluminate spinel nanoparticle as photo-anodes in quantum dot photovoltaic. By using a sol-gel auto combustion method, Al2O3 NPs, CoAl2O4, CuAl2O4, NiAl2O4, and ZnAl2O4 were successfully synthesized. The formation of Al2O3 NPs and MAl2O4 (M=Co, Cu, Ni, Zn) nanocomposite was confirmed by using several characteristics such as XRD, UV-Vis, FTIR, FE-SEM, and EDX spectra. The XRD shows that the CoAl2O4 has a smaller crystallite size (12.37 nm) than CuAl2O4, NiAl2O4, and ZnAl2O4. The formation of a single-phase spinel structure of the calcined samples at 1100 °C was confirmed by FTIR. Our studies showed that the pure Al2O3 NPs have a lower energy gap (1.37 eV) than synthesized MAl2O4 under UV-Vis irradiation. Due to the well separation between the light-generated electrons and the formed holes, the cell containing ZnAl2O4 nanocomposite with CdS QDs has the highest efficiency of 8.22% and the current density of 22.86 mA cm-2, while the cell based on NiAl2O4 as a photoelectrode, six cycles of CdS/ZnS QDs, and P-rGO as a counter electrode achieved the best (PCE) power conversion efficiency of 15.14% and the current density of 28.22 mA cm-2. Electrochemical impedance spectroscopy shows that ZnAl2O4 and NiAl2O4 nanocomposites have the highest life times of the photogenerated electrons (τn) of 11*10-2 and 96*10-3 ms, respectively, and the lowest diffusion rates (Keff) of 9.09 and 10.42 ms-1, respectively.

3.
Neuroimage Clin ; 36: 103204, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36155321

RESUMO

INTRODUCTION: White matter hyperintensities (WMHs) are common magnetic resonance imaging (MRI) findings in the aging population in general, as well as in patients with neurodegenerative diseases. They are known to exacerbate the cognitive deficits and worsen the clinical outcomes in the patients. However, it is not well-understood whether there are disease-specific differences in prevalence and distribution of WMHs in different neurodegenerative disorders. METHODS: Data included 976 participants with cross-sectional T1-weighted and fluid attenuated inversion recovery (FLAIR) MRIs from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort of the Canadian Consortium on Neurodegeneration in Aging (CCNA) with eleven distinct diagnostic groups: cognitively intact elderly (CIE), subjective cognitive impairment (SCI), mild cognitive impairment (MCI), vascular MCI (V-MCI), Alzheimer's dementia (AD), vascular AD (V-AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), cognitively intact elderly with Parkinson's disease (PD-CIE), cognitively impaired Parkinson's disease (PD-CI), and mixed dementias. WMHs were segmented using a previously validated automated technique. WMH volumes in each lobe and hemisphere were compared against matched CIE individuals, as well as each other, and between men and women. RESULTS: All cognitively impaired diagnostic groups had significantly greater overall WMH volumes than the CIE group. Vascular groups (i.e. V-MCI, V-AD, and mixed dementia) had significantly greater WMH volumes than all other groups, except for FTD, which also had significantly greater WMH volumes than all non-vascular groups. Women tended to have lower WMH burden than men in most groups and regions, controlling for age. The left frontal lobe tended to have a lower WMH burden than the right in all groups. In contrast, the right occipital lobe tended to have greater WMH volumes than the left. CONCLUSIONS: There were distinct differences in WMH prevalence and distribution across diagnostic groups, sexes, and in terms of asymmetry. WMH burden was significantly greater in all neurodegenerative dementia groups, likely encompassing areas exclusively impacted by neurodegeneration as well as areas related to cerebrovascular disease pathology.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Demência Frontotemporal , Leucoaraiose , Doenças Neurodegenerativas , Doença de Parkinson , Substância Branca , Masculino , Humanos , Feminino , Idoso , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Doença de Parkinson/patologia , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/patologia , Estudos Transversais , Canadá , Disfunção Cognitiva/patologia , Doença de Alzheimer/patologia , Imageamento por Ressonância Magnética/métodos , Envelhecimento , Demência Frontotemporal/patologia
4.
Saudi J Biol Sci ; 29(7): 103308, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35677895

RESUMO

Doxorubicin (DOX), a common antibiotic used to treat a variety of tumors, has several substantial adverse effects that limit its clinical use. As a result, finding effective protective agents to combat DOX-induced organ damage is a necessity. The current study was set to delineate the hepatoprotective role of omega-3 fatty acids (ω-3FA) against DOX-mediated acute liver damage in rats and the underlined mechanism of GSK-3ß inhibition. Five groups of rats were orally received either saline (groups 1 & 2) or ω-3FA (25, 50 and 100 mg/kg/day; groups 3, 4 & 5, respectively) for 28 consecutive days. Single DOX intraperitoneal injection (20 mg/kg) was used to induce hepatic toxicity in all groups except group 1 (negative control). Blood samples and liver tissues were collected 48-hr after injection. Our results revealed that pre-administration of ω-3FA (25, 50 and 100 mg/kg) to DOX-induced hepatic injured rats showed a significant reduction in serum hepatic injury biomarkers (ALT, AST, total and direct bilirubin) as well as hepatic contents of MDA, GSH, Nrf2 and HO-1. Additionally, hepatic PI3K, pAkt and GSK-3ß have been restored significantly in a dose-dependent manner. Furthermore, all the hepatic histopathological features have been retained upon ω-3FA treatment together with the immunostaining intensity of tumor necrosis factor-α and caspase-3. These results suggest that ω-3FA have shown a marked activation of the Nrf2/HO-1 signaling pathway and modulation of the PI3K/pAkt/GSK-3ß axis against DOX-induced hepatotoxicity.

5.
BMC Oral Health ; 22(1): 55, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246088

RESUMO

BACKGROUND AND OBJECTIVES: This study assessed the frequency of reporting suspected abuse by Egyptian dentists who have examined patients with manifestations of abuse and factors associated with this reporting within the framework of the Capability, Opportunity, Motivation, and Behaviour (COM-B) model. METHODS: A cross-sectional study included dentists practicing in Egypt in 2019. A questionnaire collected information about personal and professional background, and whether: participants received training to manage abuse, reported suspected abuse, were aware of the presence of hotlines for reporting and agencies supporting abuse victims, and eight items assessing attitude towards reporting suspected abuse. Principal Component Analysis (PCA) was used to assess the structure of attitude items. Logistic regression assessed the relationship between the dependent variable (reporting suspected abuse) and independent factors: receiving training (capability), attitude components (motivation), and awareness of the presence of hotlines and support agencies (opportunity). RESULTS: The response rate was 68.2% (821/ 1203), mean age (SD) = 29.7 (10.0) years, 43.1% had examined patients with suspected abuse last year and 4.3% reported their suspicions. PCA identified two attitude components scored out of 10: professional attitude towards reporting (mean (SD) = 6.7 (2.2)) and negative perception of workplace commitment to reporting (mean (SD) = 7.2 (2.1)). Higher odds of reporting suspected abuse were associated with better professional attitude towards reporting (AOR = 1.87, P = 0.003) and less negative perception of workplace commitment to reporting (AOR = 0.77, P = 0.04), but not with previous training (P = 0.74), awareness of the presence of victims' support agencies (P = 0.68) or a hotline (P = 0.88). CONCLUSIONS: Only a minority of dentists reported suspected abuse. Dentists who reported their suspicions had better professional attitude towards reporting and better perception of their workplace commitment to reporting. Thus, the motivation component of the COM-B framework was significantly associated with reporting suspected abuse. The present training methods to manage abuse, and dentists' unawareness of national efforts to manage the problem do not seem to encourage reporting.


Assuntos
Maus-Tratos Infantis , Motivação , Adulto , Atitude do Pessoal de Saúde , Criança , Estudos Transversais , Odontólogos , Egito , Humanos , Inquéritos e Questionários
6.
Front Neuroimaging ; 1: 940849, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37555147

RESUMO

Introduction: Cerebral microbleeds are small perivascular hemorrhages that can occur in both gray and white matter brain regions. Microbleeds are a marker of cerebrovascular pathology and are associated with an increased risk of cognitive decline and dementia. Microbleeds can be identified and manually segmented by expert radiologists and neurologists, usually from susceptibility-contrast MRI. The latter is hard to harmonize across scanners, while manual segmentation is laborious, time-consuming, and subject to interrater and intrarater variability. Automated techniques so far have shown high accuracy at a neighborhood ("patch") level at the expense of a high number of false positive voxel-wise lesions. We aimed to develop an automated, more precise microbleed segmentation tool that can use standardizable MRI contrasts. Methods: We first trained a ResNet50 network on another MRI segmentation task (cerebrospinal fluid vs. background segmentation) using T1-weighted, T2-weighted, and T2* MRIs. We then used transfer learning to train the network for the detection of microbleeds with the same contrasts. As a final step, we employed a combination of morphological operators and rules at the local lesion level to remove false positives. Manual segmentation of microbleeds from 78 participants was used to train and validate the system. We assessed the impact of patch size, freezing weights of the initial layers, mini-batch size, learning rate, and data augmentation on the performance of the Microbleed ResNet50 network. Results: The proposed method achieved high performance, with a patch-level sensitivity, specificity, and accuracy of 99.57, 99.16, and 99.93%, respectively. At a per lesion level, sensitivity, precision, and Dice similarity index values were 89.1, 20.1, and 0.28% for cortical GM; 100, 100, and 1.0% for deep GM; and 91.1, 44.3, and 0.58% for WM, respectively. Discussion: The proposed microbleed segmentation method is more suitable for the automated detection of microbleeds with high sensitivity.

7.
Brain ; 145(6): 2008-2017, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34927199

RESUMO

Diffusely abnormal white matter, characterised by biochemical changes of myelin in the absence of frank demyelination, has been associated with clinical progression in secondary progressive multiple sclerosis. However, little is known about changes of diffusely abnormal white matter over time and their relation to focal white matter lesions. The objectives of this work were: (i) to characterize the longitudinal evolution of focal white matter lesions, diffusely abnormal white matter and diffusely abnormal white matter that transforms into focal white matter lesions; and (ii) to determine whether gadolinium enhancement, known to be associated with the development of new focal white matter lesions, is also related to diffusely abnormal white matter voxels that transform into focal white matter lesions. Our data included 4220 MRI scans of 689 secondary progressive multiple sclerosis participants, followed for 156 weeks, and 2677 scans of 686 relapsing-remitting multiple sclerosis participants, followed for 96 weeks. Focal white matter lesions and diffusely abnormal white matter were segmented using a previously validated, automatic thresholding technique based on normalized T2 intensity values. Using longitudinally registered images, diffusely abnormal white matter voxels at each visit that transformed into focal white matter lesions on the last MRI scan as well as their overlap with gadolinium-enhancing lesion masks were identified. Our results showed that the average yearly rate of conversion of diffusely abnormal white matter to focal white matter lesions was 1.27 cm3 for secondary progressive multiple sclerosis and 0.80 cm3 for relapsing-remitting multiple sclerosis. Focal white matter lesions in secondary progressive multiple sclerosis participants significantly increased (t = 3.9; P = 0.0001) while diffusely abnormal white matter significantly decreased (t = -4.3 P < 0.0001) and the ratio of focal white matter lesions to diffusely abnormal white matter increased (t = 12.7; P < 0.00001). Relapsing-remitting multiple sclerosis participants also showed an increase in the focal white matter lesions to diffusely abnormal white matter ratio (t = 6.9; P < 0.00001) but without a significant change of the individual volumes. Gadolinium enhancement was associated with 7.3% and 18.7% of focal new T2 lesion formation in the infrequent scans of the relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis cohorts, respectively. In comparison, only 0.1% and 0.0% of diffusely abnormal white matter to focal white matter lesions voxels overlapped with gadolinium enhancement. We conclude that diffusely abnormal white matter transforms into focal white matter lesions over time in both relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis. Diffusely abnormal white matter appears to represent a form of pre-lesional pathology that contributes to T2 lesion volume increase over time, independent of new focal inflammation and gadolinium enhancement.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Substância Branca , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Meios de Contraste , Gadolínio , Humanos , Inflamação/patologia , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/patologia , Esclerose Múltipla Crônica Progressiva/patologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
8.
Clin Oral Investig ; 25(4): 2151-2158, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32820431

RESUMO

OBJECTIVES: The study aimed to explore the effectiveness of probiotics in the treatment of minor recurrent aphthous stomatitis (RAS). MATERIALS AND METHODS: We performed a randomized, controlled clinical study. Sixty adult (group A) and 60 children patients (group B) with diagnosis of minor RAS were included. Both groups were divided into two subgroups; AI and BI (test subgroups) and AII and BII (control subgroups). For test subgroups, probiotic lozenges were consecutively administered twice daily, for 5 days. The size and pain level of ulcers were recorded on treatment days 0, 3, and 5. The outbreak frequency of RAS within 6 months was investigated for all subgroups. RESULTS: Compared with baseline, an improvement was evident for all subgroups. However, for effectiveness in pain reduction, a statistically significant difference in favor of AI was observed for all evaluation periods when compared with control subgroup. Regarding effectiveness in ulcer size reduction, a statistically significant difference in favor of BI was observed at day 5 when compared with control subgroup. No significant difference was observed in the effectiveness index between subgroups AI and BI (test subgroups) except in effectiveness in pain reduction at day 3. The outbreak frequency decreased significantly in subgroup BI. CONCLUSIONS: Topical application of probiotics decreased pain intensity and accelerates RAS healing. The effectiveness in pain reduction is more evident in adult patients while acceleration of healing is more evident in children. CLINICAL RELEVANCE: Probiotics could be a well-tolerated, topical therapeutic agent in the treatment of minor RAS. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04383236.


Assuntos
Probióticos , Estomatite Aftosa , Adulto , Criança , Método Duplo-Cego , Humanos , Dor , Probióticos/uso terapêutico , Estomatite Aftosa/tratamento farmacológico , Comprimidos
9.
PLoS One ; 15(11): e0242175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33180794

RESUMO

This study examines the protective effects of omega-3 fatty acids (OMG), a frequently used nutritional therapy in cancer patients, against doxorubicin (DOX)-induced acute cardiorenal toxicity in rats, and evaluates the cytotoxic activity of DOX when used with OMG against breast cancer cell line. Five groups of rats were treated for 4 consecutive weeks with vehicle (groups I & II), or OMG (25, 50 or 100 mg/kg/day, po; groups III, IV & V, respectively). After twenty-four hours, the last four groups were injected with DOX (200 mg/kg, ip). In DOX-treated rats, the altered ECG, serum cardiac and renal function biomarkers, and histopathological features indicated the induction of cardiorenal toxicity. Increased oxidative and apoptotic markers in both organs was observed, with elevated renal contents of NADPH-oxidase-4 (Nox4) and renin. OMG pretreatment improved those DOX-induced impairments in a dose-dependent manner, and showed antioxidant and antiapoptotic effects with regulation of renal Nox4 expression. The in-vitro study showed preservation of the cytotoxic activity of DOX on MCF7 cell line in the presence of OMG. The data suggests OMG for protection against acute DOX-induced cardiorenal damage without affecting the latter antitumor activity. It proposes regulation of oxidative stress, Nox4 activity and apoptosis as contributing protective mechanisms.


Assuntos
Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Doxorrubicina/toxicidade , Ácidos Graxos Ômega-3/farmacologia , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Animais , Apoptose , Cardiotoxicidade , Feminino , Humanos , Rim/metabolismo , Células MCF-7 , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar
10.
Molecules ; 25(11)2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32481639

RESUMO

Protein tyrosine kinases (PTKs) are the most potential therapeutic targets for cancer. Herein, we present a sound rationale for synthesis of a series of novel 2-(methylthio), 2-(substituted alkylamino), 2-(heterocyclic substituted), 2-amino, 2,4-dioxo and 2-deoxo-5-deazaalloxazine derivatives by applying structure-based drug design (SBDD) using AutoDock 4.2. Their antitumor activities against human CCRF-HSB-2, KB, MCF-7 and HeLa have been investigated in vitro. Many 5-deazaalloxazine analogs revealed high selective activities against MCF-7 tumor cell lines (IC50: 0.17-2.17 µM) over HeLa tumor cell lines (IC50 > 100 µM). Protein kinase profiling revealed that compound 3h induced multi- targets kinase inhibition including -43% against (FAK), -40% against (CDKI) and -36% against (SCR). Moreover, the Annexin-V/PI apoptotic assay elucidate that compound 3h showed 33% and potentially 140% increase in early and late apoptosis to MCF-7 cells respectively, compared to the control. The structure-activity relationship (SAR) and molecular docking study using PTK as a target enzyme for the synthesized 7-deazaalloaxazine derivatives were investigated as potential antitumor agents. The AutoDock binding affinities of the 5-deazaalloxazine analogs into c-kit PTK (PDB code: 1t46) revealed reasonable correlations between their AutoDock binding free energy and IC50.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Flavinas/química , Células HeLa , Humanos , Células MCF-7 , Proteínas Tirosina Quinases/metabolismo , Relação Estrutura-Atividade
11.
Eur J Pharmacol ; 874: 173010, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32067934

RESUMO

Olmesartan (OLM), an angiotensin receptor blocker, was tested against diabetes/insulin resistance (IR) models associated with renal/cardiovascular complications. Methods: we tested its potential role against diabetes-induced hepatic hitches using an IR/type2 diabetic (IR/D) model induced by high fat/high fructose diet for 7 weeks â€‹+ â€‹a single sub-diabetogenic dose of streptozotocin (35mg/kg; i.p). IR/D rats were orally treated with OLM (10 â€‹mg/kg), pioglitazone (PIO; 5 or 10 â€‹mg/kg) or their combinations for 4 consecutive weeks. OLM alone opposed the detrimental effects of IR/D; it significantly improved metabolic parameters, liver function, and abated hepatic oxidative stress, and inflammatory cytokine interleukin-6 (IL-6) and its upstream mediator nuclear factor kappa B. Consequently, OLM turned off the downstream cue p-Jak2/STAT3/SOCS3. Moreover, it suppressed the elevated AGE/RAGE/p-JNK pathway and increased the PPARγ/adiponectin cue to signify its anti-inflammatory and anti-oxidant capacity (GSH, MDA). Nevertheless, co-administration of OLM to PIO showed a synergistic improvement in all the aforementioned parameters in a dose dependent manner. Additionally, OLM with PIO10 provoked a surge in hepatic PPARγ and adiponectin (5 and 6 folds) with a sharp decrease of about 85% in the NF-κB/IL-6/p-STAT3/SCOS3 pathway. These effects were confirmed by the histopathological study. In conclusion, OLM and its combination with PIO enhanced insulin sensitivity and guarded against hepatic complications associated with type 2 diabetes probably via modulating various inter-related pathways; namely, metabolic alteration, renin-angiotensin system, inflammatory trajectories, as well as oxidative stress. This study manifests the potential synergistic effects of OLM as an adjuvant therapy to the conventional antidiabetic therapies.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Imidazóis/uso terapêutico , Hepatopatias/tratamento farmacológico , Tetrazóis/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Glicemia/análise , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Produtos Finais de Glicação Avançada/metabolismo , Hipoglicemiantes/farmacologia , Imidazóis/farmacologia , Insulina/sangue , Resistência à Insulina , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Ratos Wistar , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Sistema Renina-Angiotensina , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tetrazóis/farmacologia
12.
Epilepsy Behav ; 104(Pt A): 106893, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32000097

RESUMO

Patients with diabetes and epilepsy are more prone to cognitive impairment, dementia, and even Alzheimer's disease. Diabetes-induced inflammatory process is one of the main contributing factors; however, the impact on seizure is not clear. The current study is aimed to examine the role of metformin and trimetazidine in the reduction of neuronal damage caused by inflammatory mediators and apoptotic factors in diabetic epileptic rodent model. Diabetic epileptic rats received orally either metformin (100 mg/kg) or trimetazidine (10 mg/kg) for 3 weeks exhibited reduced cognitive function and ameliorated the disturbed brain neurotransmission. Besides, they improved both the inflammatory status and the histopathologic alterations. Administration of metformin or trimetazidine ameliorated the deterioration in cognitive function in Morris water maze (MWM) and reduced seizure score. Furthermore, brain neurotransmitters glutamate and γ-aminobutyric acid (GABA) were reverted back to their normal values. Both treatments reduced the rise in inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), apoptotic markers nuclear factor-κB (NF-κB) and caspase-3, and improved the pathological photomicrograph of the hippocampus of diabetic epileptic rats. Such effects were closely correlated to the observed increase in the adenosine triphosphate and adenosine diphosphate (ATP/ADP) ratio and reduction of death-associated protein (DAP) and mammalian target of rapamycin (mTOR). In conclusion, the current study shed light on the potential neuroprotective role of metformin and trimetazidine in the amelioration of cognitive function via hindering inflammatory processes in diabetic epileptic rats.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Metformina/administração & dosagem , Trimetazidina/administração & dosagem , Administração Oral , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Hipoglicemiantes/administração & dosagem , Mediadores da Inflamação/metabolismo , Masculino , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Vasodilatadores/administração & dosagem
13.
J Med Chem ; 60(13): 5424-5437, 2017 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-28595015

RESUMO

Pan-genotypic nucleoside HCV inhibitors display a high genetic barrier to drug resistance and are the preferred direct-acting agents to achieve complete sustained virologic response in humans. Herein, we report, the discovery of a ß-d-2'-Cl,2'-F-uridine phosphoramidate nucleotide 16, as a nontoxic pan-genotypic anti-HCV agent. Phosphoramidate 16 in its 5'-triphosphate form specifically inhibited HCV NS5B polymerase with no marked inhibition of human polymerases and cellular mitochondrial RNA polymerase. Studies on the intracellular half-life of phosphoramidate 16-TP in live cells demonstrated favorable half-life of 11.6 h, suggesting once-a-day dosing. Stability in human blood and favorable metabolism in human intestinal microsomes and liver microsomes make phosphoramidate 16 a prospective candidate for further studies to establish its potential value as a new anti-HCV agent.


Assuntos
Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Pró-Fármacos/farmacologia , Ribonucleotídeos/farmacologia , Antivirais/síntese química , Antivirais/química , Células Cultivadas , Relação Dose-Resposta a Droga , Genótipo , Células Hep G2 , Hepacivirus/genética , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pró-Fármacos/síntese química , Pró-Fármacos/química , Ribonucleotídeos/síntese química , Ribonucleotídeos/química , Relação Estrutura-Atividade , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacos
14.
Nucleosides Nucleotides Nucleic Acids ; 36(1): 66-82, 2017 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-27759481

RESUMO

A novel series of tetrafluoro and hexafluoro acyclic nucleosides and their phosphoramidates were successfully prepared from commercially available 2,2,3,3-tetrafluoro-1,4-butanediol and 2,2,3,3,4,4-hexafluoro-1,5-pentanediol in four to six steps. Their ability to block HIV, HCV, HSV-1, and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM, and Vero cells was assessed.


Assuntos
Antivirais/química , Antivirais/farmacologia , Amidas/química , Animais , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Antivirais/síntese química , Técnicas de Química Sintética , Avaliação Pré-Clínica de Medicamentos/métodos , Flúor/química , Células Hep G2/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Estrutura Molecular , Nucleosídeos/síntese química , Nucleosídeos/química , Ácidos Fosfóricos/química , Células Vero/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
15.
Can J Physiol Pharmacol ; 92(6): 481-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24896301

RESUMO

Statins are the first line treatment for the management of hyperlipidemia. However, the primary adverse effect limiting their use is myopathy. This study examines the efficacy and safety of red yeast rice (RYR), a source of natural statins, as compared with atorvastatin, which is the most widely used synthetic statin. Statin interference with the endogenous synthesis of coenzyme Q10 (CoQ10) prompted the hypothesis that its deficiency may be implicated in the pathogenesis of statin-associated myopathy. Hence, the effects of combination of CoQ10 with either statin have been evaluated. Rats were rendered hyperlipidemic through feeding them a high-fat diet for 90 days, during the last 30 days of the diet they were treated daily with either atorvastatin, RYR, CoQ10, or combined regimens. Lipid profile, liver function tests, and creatine kinase were monitored after 15 and 30 days of drug treatments. Heart contents of CoQ9 and CoQ10 were assessed and histopathological examination of the liver and aortic wall was performed. RYR and CoQ10 had the advantage over atorvastatin in that they lower cholesterol without elevating creatine kinase, a hallmark of myopathy. RYR maintained normal levels of heart ubiquinones, which are essential components for energy production in muscles. In conclusion, RYR and CoQ10 may offer alternatives to overcome atorvastatin-associated myopathy.


Assuntos
Produtos Biológicos/uso terapêutico , Ácidos Heptanoicos/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Doenças Musculares/induzido quimicamente , Pirróis/efeitos adversos , Ubiquinona/análogos & derivados , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Atorvastatina , Produtos Biológicos/administração & dosagem , Terapia Combinada , Creatina Quinase/sangue , Dieta Hiperlipídica , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Lipoproteínas/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Doenças Musculares/complicações , Doenças Musculares/metabolismo , Miocárdio/metabolismo , Pirróis/uso terapêutico , Ratos , Ubiquinona/administração & dosagem , Ubiquinona/metabolismo , Ubiquinona/uso terapêutico
16.
PLoS One ; 8(10): e76207, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24098446

RESUMO

Gold nanorods (GNR) within tumor microregions are characterized by their ability to absorb near IR light and emit heat in what is called photoplasmonic effect. Yet, the efficacy of nanoparticles is limited due to intratumoral tissue distribution reasons. In addition, distribution of GNRs to normal tissue might result in non specific toxicity. In the current study, we are assessing the intratumoral and tissue distribution of PEGylated GNRs on the top of its antitumor characteristics when given intravenously or intratumoral to solid tumor bearing mice and coupled with laser photoplasmonic sessions. PEGylated GNRs with a longitudinal size of less than 100 nm were prepared with aspect ratio of 4.6 showing strong surface plasmon absorption at wavelength 800 nm. Pharmacokinetics of GNR after single I.V. administration (0.1 mg/kg) showed very short systemic circulating time (less than 3 h). On the other hand, tissue distribution of I.V. GNR (0.1 mg/kg) to normal animals showed preferential deposition in spleen tissue. Repeated administration of I.V. GNR resulted in preferential accumulation in both liver and spleen tissues. In addition, I.V. administration of GNR to Ehrlich carcinoma tumor bearing mice resulted in similar tissue distribution; tumor accumulation and anti-tumor effect compared to intratumoral administration. In conclusion, the concentration of GNR achieved within tumors microregions after I.V. administration was comparable to I.T. administration and sufficient to elicit tumoral growth arrest when coupled with laser-aided photoplasmonic treatment.


Assuntos
Carcinoma de Ehrlich/metabolismo , Ouro , Nanotubos , Administração Intravenosa , Animais , Carcinoma de Ehrlich/patologia , Carcinoma de Ehrlich/terapia , Modelos Animais de Doenças , Feminino , Ouro/química , Hipertermia Induzida , Terapia com Luz de Baixa Intensidade , Masculino , Camundongos , Nanotubos/química , Nanotubos/ultraestrutura , Polietilenoglicóis/química , Distribuição Tecidual , Carga Tumoral
17.
Artigo em Inglês | MEDLINE | ID: mdl-22499717

RESUMO

The protective effect of licorice and diclofenac sodium in doses of 50 mg/kg bwt. and 5 mg/kg bwt. respectively against liver toxicity induced by CCl4 (1ml/kg bwt.) in olive oil [1:1 (v/v)] every other day for 8 weeks and by hepatic ischemia/reperfusion in adult male albino rats was studied. Different antioxidant and liver function parameters were reported to find the protective effect of both licorice and diclofenac sodium against hepatotoxicity. Results showed that licorice protected against CCl4-induced hepatotoxicity as well as ischemia/reperfusion-induced liver injury. On the other hand, diclofenac sodium caused deleterious effects, especially in presence of CCl4, where a high mortality rate was observed.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glycyrrhiza , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/farmacologia , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Diclofenaco/farmacologia , Modelos Animais de Doenças , Quimioterapia Combinada , Testes de Função Hepática , Masculino , Ratos
18.
Nanoscale Res Lett ; 4(7): 627-34, 2009 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-20596419

RESUMO

In the present work, thermal evaporation and sol-gel coating techniques were applied to fabricate nanostructured thin ZnO films. The phase structure and surface morphology of the obtained films were investigated by X-ray diffractometer (XRD) and scanning electron microscope (SEM), respectively. The topography and 2D profile of the thin ZnO films prepared by both techniques were studied by optical profiler. The results revealed that the thermally evaporated thin film has a comparatively smoother surface of hexagonal wurtzite structure with grain size 12 nm and 51 m(2)/g. On the other hand, sol-gel films exhibited rough surface with a strong preferred orientation of 25 nm grain size and 27 m(2)/g surface area. Following deposition process, the obtained films were applied for the photodegradation of 2,4,6-trichlorophenol (TCP) in water in presence of UV irradiation. The concentrations of TCP and its intermediates produced in the solution during the photodegradation were determined by high performance liquid chromatography (HPLC) at defined irradiation times. Complete decay of TCP and its intermediates was observed after 60 min when the thermal evaporated photocatalyst was applied. However, by operating sol-gel catalyst, the concentration of intermediates initially increased and then remained constant with irradiation time. Although the degradation of TCP followed first-order kinetic for both catalysts, higher photocatalytic activity was exhibited by the thermally evaporated ZnO thin film in comparison with sol-gel one.

19.
Arzneimittelforschung ; 55(12): 738-43, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16430027

RESUMO

Some new substituted quinoxaline and furo[2,3-b]quinoxaline derivatives have been synthesized and tested for their anti-inflammatory and analgesic activities and for their ulcerogenic potential. The pharmacological evaluation of selected synthesized compounds revealed that 5a was equipotent and compounds 3, 4b, 4e and 5b possessed strong anti-inflammatory activity in chronic inflammatory models compared with indometacin (CAS 53-86-1) as reference drug. In addition, compound 4a was the safest one and the others showed little ulcerogenic activity. All the tested compounds showed moderate analgesic activity compared to the reference drug.


Assuntos
Analgésicos não Narcóticos/síntese química , Analgésicos não Narcóticos/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Quinoxalinas/síntese química , Quinoxalinas/farmacologia , Úlcera Gástrica/induzido quimicamente , Analgésicos não Narcóticos/efeitos adversos , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Carragenina , Edema/induzido quimicamente , Edema/prevenção & controle , Feminino , Indicadores e Reagentes , Masculino , Medição da Dor/efeitos dos fármacos , Quinoxalinas/efeitos adversos , Ratos , Ratos Sprague-Dawley
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