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1.
J Fluoresc ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865063

RESUMO

Pemetrexed is a chemotherapeutic medicine, under the trade name Alimta. Malignant pleural mesothelioma patients. Its application in lung cancer has been studied. Here in, a second spectrofluorimetric method was advanced for quantifying of Pemetrexed in pharmaceutical formulation and spiked human plasma. That method depends on fluorescence derivatization of Pemetrexed with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) at 75 °C in a (pH 9) of borate buffer to produce a fluorescent derivative which can be detected at 520 nm afterwards excitation at 460 nm. The method has been validated using ICH criteria, and it demonstrated linearity in a range of 2-120 ngmL-1. The proposed method was applied precisely and accurately for quantifying Pemetrexed within pharmaceutical formulation and spiking human plasma without any interferences. Moreover, the method's sustainability was evaluated and compared to the published method using two greenness assessment tools termed analytical eco-scale and Analytical GREENness (AGREE). That findings suggest that the method is more sustainable than the published method.

2.
Luminescence ; 39(3): e4704, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38433336

RESUMO

Darolutamide is an oral nonsteroidal androgen receptor antagonist used to delay the process of prostate cancer to metastatic disease and to increase the quality of life for people with advanced prostate cancer. Here, a second spectrofluorimetric method was advanced for quantifying Darolutamide in pharmaceutical formulation and spiked human plasma. This method depends on the fluorescence derivatization of Darolutamide with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) at 75°C in a (pH 9) of borate buffer to produce a fluorescent derivative that can be detected at 520 nm after excitation at 460 nm. The method has been validated using ICH criteria, and it demonstrated linearity in the range 5-200 ng ml-1 . The limit of detection (LOD) and limit of quantitation (LOQ) were 1.15 and 3.84 nm, respectively. The proposed method was applied precisely and accurately for quantifying Darolutamide within the pharmaceutical formulation and spiking human plasma without any interferences. Moreover, the method's sustainability was evaluated and compared with the published method using two greenness assessment tools termed analytical eco-scale and Analytical GREEnness (AGREE). These findings suggest that the method is more sustainable than the published method.


Assuntos
4-Cloro-7-nitrobenzofurazano , Antineoplásicos , Neoplasias da Próstata , Pirazóis , Masculino , Humanos , Composição de Medicamentos , Qualidade de Vida , Espectrometria de Fluorescência
3.
Luminescence ; 38(9): 1583-1590, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37325939

RESUMO

A spectrofluorimetric approach that is sensitive, simple, validated, and cost-effective has been proposed for the estimation of amlodipine (AML) and perindopril (PER) in their bulk powders, pharmaceutical formulations, and spiked human plasma. The recommended approach utilized the quantitative quenching effect of the two cited drugs on the fluorescence intensity of erythrosine B, as a result of complex binary reactions among each drug with erythrosine B at pH 3.5 (Teorell and Stenhagen buffer). The quenching of erythrosine B fluorescence was recorded at 554 nm after excitation at 527 nm. The calibration curve was detected in the range 0.25-3.0 µg ml-1 , with a correlation coefficient of 0.9996 for AML, and 0.1-1.5 µg ml-1 , with a correlation coefficient of 0.9996 for PER. The established spectrofluorimetric approach was validated for the estimation of the cited drugs with high sensitivity regarding International Council on Harmonization guidelines. Therefore, the established approach could be utilized for quality control of the cited drugs in their pharmaceutical formulations.


Assuntos
Anlodipino , Leucemia Mieloide Aguda , Humanos , Perindopril , Eritrosina , Espectrometria de Fluorescência , Preparações Farmacêuticas
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 299: 122838, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37187147

RESUMO

Finasteride and tadalafil are combined in a pharmaceutical capsules called Entadfi™, that has received FAD approval. It was indicated for the management of male benign prostatic hyperplasia-related urinary tract issues. In the current study, finasteride and tadalafil concentrations in raw form, laboratory prepared mixtures, pharmaceutical preparation and spiked human plasma were all quantitatively estimated using a sensitive synchronized fluorescence spectroscopic approach united with first derivative. When excited at 260 nm, finasteride display its emission at 320 nm. Yet, when excited at 280 nm, tadalafil displayed its emission at 340 nm. The application of micellar surfactant as sodium dodecyl sulphate (SDS) significantly increased the fluorescence intensity.The overlapping of the fluorescence spectra was entirely eliminated by derivatizing the synchronous spectra to the first derivative, which also made it possible to simultaneously quantify the cited drugs. Without interfering with one another, the first-order synchronous spectra of tadalafil and finasteride at 320 and 330 nm, respectively. The approach revealed linearity alongside an acceptable correlation coefficient for finasteride and tadalafil concentrations over the range of 10 -50 ng/mL. That approach was utilized to estimation of the cited drugs in dosage forms, simultaneously with %recoveries for tadalafil and finasteride of 99.62 ± 0.78 and 100.19 ± 0.60, respectively. Also, four various tools, the national environmental method index, the AGREE evaluation method, the green analytical procedure index and the analytical eco-scale were used to evaluate how environmentally friendly the given approach was. With regard to the metrics of the greenness aspects, the proposed approach appeared to be better than the previously published spectrophotometric methods and HPLC.


Assuntos
Finasterida , Hiperplasia Prostática , Humanos , Masculino , Tadalafila , Fluorescência , Hiperplasia Prostática/tratamento farmacológico , Cápsulas , Espectrometria de Fluorescência
5.
Luminescence ; 38(6): 672-679, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37078125

RESUMO

Pharmaceutical product quality control (QC) needs quick, sensitive and economical procedures to deliver high throughput at low cost, which is the key factor considered by such economic facilities. To lessen the risky effects of research laboratories, researchers must take into account the ecological impacts. α-Mangostin (MAG) exhibit anti-inflammatory, antioxidant, anticancer, anti-allergic, antibacterial, antifungal, antiviral and antimalarial activities. Based on the spectrofluorimetric approach, a novel straightforward, sensitive and environmentally friendly method for MAG determination was developed and validated. Many variables were investigated to improve MAG native fluorescence, including solvent type, buffers, pH and additional surfactants. The best MAG fluorescence sensitivity was found in Britton-Robinson buffer (pH 4) at 450 nm after irradiation at 350 nm in the concentration range of 5-50 ng ml-1 . The technique was successfully used to determine the presence of MAG in both its approved dose forms and in samples of spiked human plasma, as per FDA standards for validation. According to their evaluation on two recent greenness criteria (GAPI [Green Analytical Procedure Index] and AGREE [Analytical GREEnness]), the suggested approach has been shown to be environmentally beneficial because it normally uses biodegradable chemicals in solvent-free aqueous phases.


Assuntos
Micelas , Xantonas , Humanos , Antioxidantes/farmacologia , Espectrometria de Fluorescência/métodos , Xantonas/farmacologia , Solventes
6.
Luminescence ; 38(1): 64-70, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36394880

RESUMO

A recent antineoplastic medication is pemetrexed, this medicine is now being developed and produced on a large scale, thus approaches for quality control are urgently needed. Spectrofluorimetric guidelines for the simple estimation of pemetrexed were validated. Pemetrexed's assay depends on observations of its native fluorescence at wavelengths 275/450 nm and pH 4. The proposed approach was also used to identify the examined drug in both its formulation and in human plasma that had been spiked.


Assuntos
Antineoplásicos , Humanos , Pemetrexede , Espectrometria de Fluorescência , Preparações Farmacêuticas
7.
RSC Adv ; 12(17): 10198-10203, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-36200125

RESUMO

A simple, new, green, and sensitive approach was established and validated for assay of the recently approved antineoplastic medication; darolutamide (DAR) in its authentic form, pharmaceutical formulation, and biological fluids fluorimetrically. This experiment relied on the native fluorescence of the cited drug and detects the ideal solvent utilized throughout the approach. The proposed approach was validated regarding linearity, accuracy, and precision. The calibration graph showed linearity over the range of 0.1-2.0 µg mL-1. The limit of detection and quantitation (LOD and LOQ) were 0.032 µg mL-1 and 0.09 µg mL-1, respectively. Because of the approach's high sensitivity, it was decided to spike the mentioned drug in plasma and urine samples. At last, checking for content uniformity was performed regarding the United States Pharmacopoeia (USP) by adjusting the proposed approach.

8.
Luminescence ; 37(4): 656-664, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35142060

RESUMO

An approved, straightforward, fast, and delicate spectrofluorimetric strategy was developed for the estimation of tepotinib (TEPO), sotorasib (SOTO), and darolutamide (DARO) as new antineoplastic drugs. The spectrofluorimetric strategy was based on quantitative fluorescence quenching of MER at 538 nm after being excited at 350 nm by the addition of the cited drugs in the presence of acetate buffer (pH 3.5). The degree of fluorescence quenching was directly proportional to the concentrations of the cited drugs within the concentration range of 0.5-10.0, 0.2-10, and 0.4-10.0 µg ml-1 for TEPO, SOTO, and DARO, respectively. Mean ± standard deviation (SD) were calculated for the studied drugs as follows; 99.9 ± 0.87, 99.72 ± 1.08, and 100.21 ± 1.44, for TEPO, SOTO, and DARO, respectively. Limit of detection (LOD) values were 0.16, 0.05, and 0.11 µg ml-1 , whereas limit of quantitation (LOQ) values were 0.5, 0.15, and 0.36 µg ml-1 for TEPO, SOTO, and DARO, respectively. Statistical comparison through detailed strategies produced greater understanding and found that there were no noteworthy contrasts in exactness and exactness between strategies. The proposed strategy was used effectively to analyze the measurement of different forms of the examined drugs. Moreover, the recommended fluorimetric strategy was used for examination of TEPO, SOTO, and DARO in human plasma and urine tests.


Assuntos
Antineoplásicos , Merbromina , Humanos , Piperazinas , Piperidinas , Pirazóis , Piridazinas , Piridinas , Pirimidinas , Espectrometria de Fluorescência
9.
BMC Med Inform Decis Mak ; 21(1): 223, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294092

RESUMO

BACKGROUND: Testing a hypothesis for 'factors-outcome effect' is a common quest, but standard statistical regression analysis tools are rendered ineffective by data contaminated with too many noisy variables. Expert Systems (ES) can provide an alternative methodology in analysing data to identify variables with the highest correlation to the outcome. By applying their effective machine learning (ML) abilities, significant research time and costs can be saved. The study aims to systematically review the applications of ES in urological research and their methodological models for effective multi-variate analysis. Their domains, development and validity will be identified. METHODS: The PRISMA methodology was applied to formulate an effective method for data gathering and analysis. This study search included seven most relevant information sources: WEB OF SCIENCE, EMBASE, BIOSIS CITATION INDEX, SCOPUS, PUBMED, Google Scholar and MEDLINE. Eligible articles were included if they applied one of the known ML models for a clear urological research question involving multivariate analysis. Only articles with pertinent research methods in ES models were included. The analysed data included the system model, applications, input/output variables, target user, validation, and outcomes. Both ML models and the variable analysis were comparatively reported for each system. RESULTS: The search identified n = 1087 articles from all databases and n = 712 were eligible for examination against inclusion criteria. A total of 168 systems were finally included and systematically analysed demonstrating a recent increase in uptake of ES in academic urology in particular artificial neural networks with 31 systems. Most of the systems were applied in urological oncology (prostate cancer = 15, bladder cancer = 13) where diagnostic, prognostic and survival predictor markers were investigated. Due to the heterogeneity of models and their statistical tests, a meta-analysis was not feasible. CONCLUSION: ES utility offers an effective ML potential and their applications in research have demonstrated a valid model for multi-variate analysis. The complexity of their development can challenge their uptake in urological clinics whilst the limitation of the statistical tools in this domain has created a gap for further research studies. Integration of computer scientists in academic units has promoted the use of ES in clinical urological research.


Assuntos
Neoplasias da Próstata , Urologia , Sistemas Inteligentes , Humanos , MEDLINE , Aprendizado de Máquina , Masculino
10.
Life Sci ; 277: 119506, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33865881

RESUMO

Diclofenac, one of the most commonly used non-steroidal anti-inflammatory drugs, leads to severe adverse effects on the kidneys. The aim of the present study was to investigate the potential pretreatment effect of phosphodiesterase (1, 3 & 5) inhibitors on diclofenac-induced acute renal failure in rats. Rats orally received pentoxifylline (100 mg/kg), vinpocetine (20 mg/kg), cilostazol (50 mg/kg), or sildenafil (5 mg/kg) once per day for 6 consecutive days. Diclofenac (15 mg/kg) was injected on day-4, -5 and -6 in all groups except normal control group. The used phosphodiesterase inhibitors significantly reduced the diclofenac-induced elevation in the serum levels of blood urea nitrogen, creatinine and cystatin C. Moreover, the renal tissue contents of tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB as well as the protein expression of toll-like receptor (TLR) 4 and high mobility group box (HMGB) 1 were markedly reduced by the used phosphodiesterase inhibitors, as compared to the diclofenac control. This was reflected on the marked improvement in histopathological changes induced by diclofenac. Sildenafil showed the best protection regarding TNF-α and NF-κB, while cilostazol showed the best results regarding TLR4, HMGB1 and histopathological examination. This study revealed the good protective effect of these phosphodiesterase inhibitors against diclofenac-induced acute renal failure.


Assuntos
Injúria Renal Aguda/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Animais , Nitrogênio da Ureia Sanguínea , Cilostazol/farmacologia , Creatinina/metabolismo , Diclofenaco/efeitos adversos , Diclofenaco/farmacologia , Rim/patologia , Masculino , NF-kappa B/metabolismo , Pentoxifilina/farmacologia , Inibidores de Fosfodiesterase/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Ratos , Ratos Wistar , Citrato de Sildenafila/farmacologia , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Alcaloides de Vinca/farmacologia
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 255: 119648, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33744839

RESUMO

For the treatment of internal and external hemorrhoids, policresulen (POL) and cinchocaine hydrochloride (CIN) are used in combination. Using a new, simple, fast, and economical first-derivative synchronous fluorescence spectroscopic process, both drugs were simultaneously determined and validated. At Δλ60 nm and with a scanning rate of 600 nm/min, methanol was used as the solvent for both products. In the concentration ranges of 5.0-21.0 µg mL-1 and 0.5-6.0 µg mL-1 for POL and CIN, the amplitude-concentration plots were rectilinear. The detection limits were found to be 0.770 µg mL-1 and 0.118 µg mL-1 and the quantitation limits for POL and CIN were 2.541 µg mL-1 and 0.391 µg mL-1. To evaluate all compounds in synthetic mixtures and medicinal dosage types, the proposed method has been successfully applied. These findings were in line with the results obtained using high-performance thin layer chromatography, the comparison process.


Assuntos
Dibucaína , Cresóis , Combinação de Medicamentos , Formaldeído , Pomadas , Espectrometria de Fluorescência , Supositórios
12.
Spectrochim Acta A Mol Biomol Spectrosc ; 251: 119428, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33485244

RESUMO

A exceedingly touchy resonance Rayleigh scattering (RRS) strategy for the assurance of nilotinib (NILO) was introduced. In the pH 3.4 acetate buffer solution, NILO reacted with erythrosine B to produce an ion-association complex, which increased the RRS intensity of the studied system. The enhanced RRS intensity (ΔI) was linearly proportional to the concentration of NILO, the linear range of the method was 0.1-1.0 µg/mL and the detection limit (DL) was 0.025 µg/mL. In like manner, this test was connected to distinguish the concentration of NILO in capsules and human plasma with palatable comes about.


Assuntos
Antineoplásicos , Eritrosina , Cápsulas , Humanos , Concentração de Íons de Hidrogênio , Pirimidinas , Espalhamento de Radiação , Espectrometria de Fluorescência
13.
J Gynecol Obstet Hum Reprod ; 50(5): 101969, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33147492

RESUMO

OBJECTIVES: To evaluate results of laparoscopic adhesiolysis in patients with post cesarean infertility regards restoration of the fertility and achievement of pregnancy. To identify a group of patients who should primarily be offered laparoscopic adhesiolysis and those who should be treated by IVF. DESIGN: Randomized prospective clinical trial MATERIALS AND METHODS: 184 patients with secondary infertility diagnosed to have periadnexal and pelvic adhesions, were randomly allocated into two groups: group I (92 cases) treated by laparoscopic adhesiolysis and group II (92 cases) who treated for a year by controlled ovarian stimulation and IUI up to 3 trials. Diagnostic work-up of infertility was carried out denoting normal semen, patent both tubes at HSG, and ovulatory at ovulation testing with normal hormonal profile. The outcomes, cumulative pregnancy rates calculated for each group after one year. RESULTS: According to the adhesions, the patients classified into 4 groups: 8 cases inoperable, 43 cases with mild type adhesions, 26 cases with moderate type adhesions, and 5 cases with severe type adhesions. The patients followed up postoperatively for year. Overall pregnancy rate 54.35 %. For patients with mild adhesions 76.7%, for patients with moderate adhesions 61.5%, and for patients with severe adhesions 20%. Complications present in (1.57%), cost is (125.7-180.9 $). Over all pregnancy rate was 11.96% in group (II) CONCLUSIONS: laparoscopic adhesiolysis is the method of choice for dealing with mild to moderate periadnexal adhesions after C.S. The pregnancy outcome after lysis of severe periadnexal adhesions is poor. So, such patients are best treated by IVF.


Assuntos
Cesárea/efeitos adversos , Fertilização in vitro , Infertilidade Feminina/etiologia , Laparoscopia , Complicações Pós-Operatórias/cirurgia , Adulto , Feminino , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/cirurgia , Análise de Intenção de Tratamento , Indução da Ovulação , Pelve , Complicações Pós-Operatórias/diagnóstico , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Estudos Prospectivos , Aderências Teciduais/classificação , Aderências Teciduais/cirurgia , Resultado do Tratamento , Adulto Jovem
14.
BJU Int ; 122(3): 418-426, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29393997

RESUMO

OBJECTIVE: To test a computer-led follow-up service for prostate cancer in two UK hospitals; the testing aimed to validate the computer expert system in making clinical decisions according to the individual patient's clinical need with a valid model accurately identify patients with disease recurrence or treatment failure based on their blood test and clinical picture. PATIENTS AND METHODS: A clinical-decision support system (CDSS) was developed from European (European Association of Urology) and national (National Institute for Health and Care Excellence) guidelines along with knowledge acquired from Urologists. This model was then applied in two UK hospitals to review patients after prostate cancer treatment. These patients' data (n = 200) were then reviewed by two independent urology consultants (blinded from the CDSS and the other consultant's rating) and the agreement was calculated by kappa statistics for validation. The second endpoint was to verify the system by estimating the system reliability. RESULTS: The two individual urology consultants identified 12% and 15% of the patients to have potential disease progression and recommended their referral to urology care. The kappa coefficient for the agreement between the CDSS and the two consultants was 0.81 (P < 0.001) and 0.84 (P < 0.001). The agreement amongst both specialist was also high with k = 0.83 (P < 0.001). The system reliability was estimated on all cases and this demonstrated 100% repeatability of the decisions. CONCLUSION: A CDSS follow-up is a valid model for providing safe follow-up for prostate cancer.


Assuntos
Assistência ao Convalescente/métodos , Sistemas de Apoio a Decisões Clínicas , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Consultores , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Próstata/patologia , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes , Reino Unido
15.
Braz. J. Pharm. Sci. (Online) ; 54(3): e17565, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-974411

RESUMO

The aim of this work is to evaluate simple, sensitive, effective and validated procedures for the determination of cefotaxime, cefoperazone, ceftazidime and cefadroxil. In this study, the methods based on the ability of the cited drugs to reduce Ag+ ions to silver nanoparticles (Ag-NPs) in the presence of Polyvinyl Pyrrolidone (PVP) as a stabilizing agent producing very intense surface plasmon resonance peak of Ag-NPs (λmax. = 410-430 nm). The plasmon absorbance of the Ag-NPs allows the quantitative spectrophotometric determination of the cited drugs. The calibration curves are linear with concentration ranges of 0.4-3.2, 1-8, 0.5-4.0 and 1.5-9.0 µg/mL for cefotaxime, cefoperazone, ceftazidime and cefadroxil, respectively. Apparent molar absorptivity, detection and quantitative limits are calculated. Applications of the proposed methods to representative pharmaceutical formulations are successfully presented. The extracellular synthesis of nanoparticles is fast, and the method doesn't require various elaborate treatments and tedious extraction procedures.


Assuntos
Cefadroxila/análise , Cefoperazona/análise , Cefotaxima/análise , Ceftazidima/análise , Nanopartículas Metálicas/estatística & dados numéricos , Ressonância de Plasmônio de Superfície/métodos , Estudo de Validação
16.
Sci Rep ; 7(1): 7139, 2017 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-28769047

RESUMO

Butyrate and niacin are produced by gut microbiota, however butyrate has received most attention for its effects on colonic health. The present study aimed at exploring the effect of niacin on experimental colitis as well as throwing some light on the ability of niacin to modulate angiogenesis which plays a crucial role of in the pathogenesis of inflammatory bowel disease. Rats were given niacin for 2 weeks. On day 8, colitis was induced by intrarectal administration of iodoacetamide. Rats were sacrificed on day 15 and colonic damage was assessed macroscopically and histologically. Colonic myeloperoxidase (MPO), tumour necrosis factor (TNF)-α, interleukin (IL)-10, vascular endothelial growth factor (VEGF), angiostatin and endostatin levels were determined. Niacin attenuated the severity of colitis as demonstrated by a decrease in weight loss, colonic wet weight and MPO activity. Iodoacetamide-induced rise in the colonic levels of TNF-α, VEGF, angiostatin and endostatin was reversed by niacin. Moreover, niacin normalized IL-10 level in colon. Mepenzolate bromide, a GPR109A receptor blocker, abolished the beneficial effects of niacin on body weight, colon wet weight as well as colonic levels of MPO and VEGF. Therefore, niacin was effective against iodoacetamide-induced colitis through ameliorating pathologic angiogenesis and inflammatory changes in a GPR109A-dependent manner.


Assuntos
Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Inflamação/metabolismo , Inflamação/patologia , Neovascularização Patológica/metabolismo , Niacina/metabolismo , Animais , Biomarcadores , Biópsia , Peso Corporal , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/etiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Knockout , Neovascularização Patológica/tratamento farmacológico , Niacina/farmacologia , Tamanho do Órgão , Ratos
17.
Mol Neurobiol ; 53(2): 810-817, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25502462

RESUMO

The recent emergence of ursodeoxycholic acid (UDCA) as a contender in modifying neurotoxicity in human dopaminergic cells as well as its recognized anti-apoptotic and anti-inflammatory potentials in various hepatic pathologies raised impetus in investigating its anti-parkinsonian effect in rat rotenone model. UDCA prominently improved motor performance in the open field test and halted the decline in the striatal dopamine content. Meanwhile, it improved mitochondrial function as verified by elevation of ATP associated with preservation of mitochondrial integrity as portrayed in the electron microscope examination. In addition, through its anti-inflammatory potential, UDCA reduced the rotenone-induced nuclear factor-κB expression and tumor necrosis factor alpha level. Furthermore, UDCA amended alterations in Bax and Bcl-2 and reduced the activities of caspase-8, caspase-9, and caspase-3, indicating that it suppressed rotenone-induced apoptosis via modulating both intrinsic and extrinsic pathways. In conclusion, UDCA can be introduced as a novel approach for the management of Parkinson's disease via anti-apoptotic and anti-inflammatory mechanisms. These effects are probably linked to dopamine synthesis and mitochondrial regulation.


Assuntos
Apoptose/efeitos dos fármacos , Mitocôndrias/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Ácido Ursodesoxicólico/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Caspases/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Neostriado/efeitos dos fármacos , Neostriado/enzimologia , Neostriado/metabolismo , Neostriado/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Neurônios/ultraestrutura , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Rotenona
18.
Nutr Res ; 34(11): 982-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25439027

RESUMO

Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome, with liver transplantation being the only effective therapy. Sulforaphane (SFN) is a natural compound that is extracted from cruciferous vegetables and possesses potent anti-inflammatory, antioxidant, and anticancer activities. This study was designed to test the hypothesis that SFN (3 mg/kg) may protect against FHF induced in rats by administering a combination of D-galactosamine (GalN; 300 mg/kg) and lipopolysaccharide (LPS; 30 µg/kg). The rats were given a single intraperitoneal injection of SFN, 1 hour before the FHF induction. Sulforaphane reduced the mortality and alleviated the pathological liver injury. In addition, SFN significantly reduced the increase in serum aminotransferase activities and lipid peroxidation. The glutathione content decreased in the GalN/LPS group, and this decrease was attenuated by SFN. Increases in serum tumor necrosis factor α, interleukin-6, and interleukin-10, which were observed in GalN/LPS-treated rats, were significantly reduced after using SFN. The GalN/LPS treatment increased the expression of superoxide dismutase-1, glutathione peroxidase 2, catalase, and heme oxygenase-1 genes. Sulforaphane inhibited the induction of reactive oxygen species scavenging proteins. Moreover, SFN inhibited GalN/LPS-induced caspase-3 activation and suppressed FAS and FASL expression. These findings suggest that SFN alleviates GalN/LPS-induced liver injury, possibly by exerting antioxidant, anti-inflammatory, and antiapoptotic effects and modulating certain antioxidant defense enzymes.


Assuntos
Galactosamina/efeitos adversos , Isotiocianatos/farmacologia , Lipopolissacarídeos/efeitos adversos , Falência Hepática Aguda/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Catalase/sangue , Proteína Ligante Fas/genética , Proteína Ligante Fas/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/sangue , Heme Oxigenase-1/sangue , Injeções Intraperitoneais , Interleucina-10/sangue , Interleucina-6/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Sulfóxidos , Superóxido Dismutase/sangue , Superóxido Dismutase-1 , Taxa de Sobrevida , Transaminases/sangue , Fator de Necrose Tumoral alfa/sangue , Receptor fas/genética , Receptor fas/metabolismo
19.
J Pharm Pharmacol ; 66(10): 1439-50, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24944002

RESUMO

OBJECTIVES: The solid-state interactions of fused mixtures nimesulide (ND) with polyethylene glycol (PEG) 4000, urea or mannitol were studied through constructing thaw-melt phase equilibrium diagrams. METHODS: The solid-state characteristics were investigated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Various types of interactions were identified such as the formation of a eutectic system of ND-PEG 4000, monotectic system of ND-urea and complete solid immiscibility of ND with mannitol. The effects of carrier concentrations on the equilibrium solubility and in-vitro dissolution characteristics were studied. KEY FINDINGS: Linear increases (R(2) > 0.99) in the aqueous solubility of ND in various concentrations of PEG 4000 and urea were obtained, whereas mannitol did not exhibit any effect on the solubility of ND. Similar trends were obtained with the dissolution efficiency of the fused mixtures of ND with PEG 4000 and urea compared with the corresponding physical mixtures and untreated drug. The analgesic effects of untreated ND and the selected formulations were investigated by evaluating the drug's ability to inhibit the acetic acid-induced writhing response. CONCLUSIONS: The analgesic effect of ND in a eutectic mixture with PEG 4000 and a monotectic mixture with urea was potentiated by 3.2 and 2.7-fold respectively compared with the untreated drug.


Assuntos
Inibidores de Ciclo-Oxigenase/administração & dosagem , Portadores de Fármacos/química , Excipientes/química , Polietilenoglicóis/química , Sulfonamidas/administração & dosagem , Ureia/química , Água/química , Ácido Acético , Animais , Varredura Diferencial de Calorimetria , Química Farmacêutica , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Camundongos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Povidona/química , Solubilidade , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Difração de Raios X
20.
Environ Toxicol Pharmacol ; 34(3): 849-57, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23021633

RESUMO

Dibromoacetonitrile (DBAN) is a disinfection by-product of water chlorination. Epidemiological studies indicate that it might present a potential hazard to human health. The present study aimed to investigate the possible neurotoxicity of DBAN in rats and possible protection by taurine. Based on initial dose-response experiment, DBAN (60 mg/kg) was administrated orally for 7 days. DBAN administration significantly impaired behavior of rats. Further, DBAN produced significant decrease of monoamines, γ-aminobutyric acid (GABA), glutamate contents, acetylcholinestrase (AChE) and aspartate aminotransferase (AST) activities, in rat brain. On the other hand, a significant increase in malondialdehyde (MDA), nitric oxide (NO) contents and lactic dehydrogenase (LDH) activity was observed. Co-administration of taurine (200mg/kg, i.p.) with DBAN mitigated most tested parameters. In conclusion, the present study indicates that DBAN has the propensity to cause significant oxidative damage in rat brain. However, taurine has a promising role in attenuating the obtained hazardous effects of DBAN.


Assuntos
Acetonitrilas/toxicidade , Antioxidantes/farmacologia , Desinfetantes/toxicidade , Taurina/farmacologia , Animais , Aspartato Aminotransferases/metabolismo , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ácido gama-Aminobutírico/metabolismo
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