Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.258
Filtrar
1.
Anticancer Res ; 40(1): 253-259, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892574

RESUMO

BACKGROUND/AIM: The aim of the study was to compare the MDA (malonidialdehyde) plasma concentrations versus CAT (catalase)/NT (nitrotyrosine) plasma concentrations, patient satisfaction and pain score at rest/pressure to the wound area in laparotomy patients with rectus sheath block (RSB) analgesia. PATIENTS AND METHODS: Initially, 56 patients were randomized to four groups; control group (n=12), single-dose (n=16), repeated-dose (n=12) and continuous infusion (n=16) RSB analgesia groups. The plasma concentrations of CAT, NT and MDA markers were measured just before, immediately after and 24 h after operation. RESULTS: The RSB analgesia enhanced significantly patient satisfaction (p=0.001). The plasma MDA decreased immediately after operation (POP1) and the postoperative decrease between the preoperative and the POP1 values in the MDA marker were statistically significant (p<0.001). In linear mixed model, the time effect in both the single group and in the benign group in plasma NT biomarker was statistically significant (p=0.001, p=0.013, respectively). The median plasma MDA concentrations (ng/ml) following surgery were significantly lower in patients with cancer versus patients with benign disease (589 vs. 852, p=0.021). Jitterplots of the individual plasma NT versus plasma MDA showed that there was significant correlation in benign and cancer patients (r=0.347, p<0.001). CONCLUSION: Plasma MDA decreased significantly after operation in all patients and cancer patients had significantly lower MDA concentrations following surgery than patients with benign disease.


Assuntos
Analgesia , Laparotomia , Malondialdeído/sangue , Neoplasias/sangue , Bloqueio Nervoso , Catalase/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tirosina/análogos & derivados , Tirosina/sangue
2.
Life Sci ; 235: 116858, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31505195

RESUMO

AIMS: The current study was conducted to investigate the potential protective effects of hesperidin and its possible mechanisms of action on pancreatic ß-cells in diabetes. MAIN METHODS: Male Sprague Dawley rats were made diabetic using 65 mg/kg intraperitoneal injection of streptozotocin, and then administered daily with 100 mg/kg of hesperidin over 4 weeks. On conclusion of the experiment, blood and pancreatic tissue were collected to determine the function of ß-cells, apoptosis, oxidative stress, ER stress, and inflammation. KEY FINDINGS: Treatment of diabetic rats with hesperidin, significantly decreased fasting blood glucose and food intake, along with increased body weight, serum and pancreatic insulin levels, and pancreatic-duodenal homeobox-1 (PDX-1) protein expression. The beneficial roles of hesperidin on diabetic pancreatic ß-cells exhibited an increment in antioxidant SOD and GPx activities, and a decrement in nitrotyrosine as well as malondialdehyde (MDA) levels. Additionally, the elevated concentration of TNF-α and expressions of ER stress maker GRP78 and CHOP proteins in the pancreas of diabetic rats were significantly diminished by hesperidin treatment. Furthermore, hesperidin effectively modulated expressions of apoptosis-regulatory proteins in diabetic rat pancreas, as revealed by upregulating anti-apoptotic Bcl-xL; with a concomitant downregulating pro-apoptotic Bax, cleaved caspase-3, and inhibiting the activation of DNA repair protein poly (ADP-ribose) polymerase (PARP). SIGNIFICANCE: Collectively, these findings suggest that hesperidin may have the potential to protect pancreatic ß-cells and improve their function by suppressing oxidative and ER stress, along with activating its antioxidant, anti-inflammatory, and anti-apoptotic effects.


Assuntos
Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/prevenção & controle , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hesperidina/farmacologia , Células Secretoras de Insulina/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de Homeodomínio/biossíntese , Inflamação , Insulina/sangue , Insulina/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Superóxido Dismutase/metabolismo , Transativadores/biossíntese , Fator de Transcrição CHOP/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo
3.
Clin Nucl Med ; 44(10): e581-e582, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31348085

RESUMO

A variety of neoplastic and nonneoplastic conditions involve the corpus callosum, which may result in a "butterfly" appearance on conventional MRI. Typically, that pattern shows a bilateral and heterogeneous contrast enhancement of the lesion, occasionally with central nonenhancing areas indicating intralesional necrosis. In contrast, anaplastic gliomas may show only minimal or even a lack of contrast enhancement on MRI. We here report neuroimaging findings in a 69-year-old man with a "butterfly" pattern on dynamic FET [O-(2-[F]-fluoroethyl)-L-tyrosine] PET and the diagnosis of an anaplastic astrocytoma (WHO grade III; IDH-1/-2 wildtype, no 1p/19q co-deletion) but without typical MRI contrast enhancement.


Assuntos
Astrocitoma/diagnóstico por imagem , Astrocitoma/enzimologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/enzimologia , Isocitrato Desidrogenase/metabolismo , Tomografia por Emissão de Pósitrons , Tirosina/análogos & derivados , Idoso , Astrocitoma/genética , Astrocitoma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Humanos , Isocitrato Desidrogenase/genética , Imagem por Ressonância Magnética , Masculino
4.
Clin Nucl Med ; 44(9): 695-701, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31274552

RESUMO

PURPOSE: PET/CT using O-(2-[F]fluoroethyl)-L-tyrosine (F-FET) has proven valuable in differentiating tumor recurrence and progression from therapy-induced changes. This study aimed to investigate the diagnostic performance of several analytic approaches in the setting of suspected late pseudoprogression (PsP) in glioblastoma multiforme (GBM). METHODS: Retrospective analysis of tumor recurrence was performed in 36 patients with histopathologically confirmed GBM and suspicion of recurrence/disease progression more than 12 weeks from cessation of irradiation based on MRI and Response Assessment in Neuro-Oncology working group criteria. For differentiation of late PsP from true tumor recurrence, images were analyzed semiquantitatively employing tumor-to-brain ratios using 5 different approaches for tumor and normal brain reference region definition, respectively. Histopathology and/or clinical and imaging follow-up served as reference. Respective areas under the receiver operating characteristic curve were compared. RESULTS: F-FET PET was able to reliably differentiate PsP from true tumor progression with areas under the receiver operating characteristic curve ranging from 0.80 to 0.88 (all P < 0.01). Irrespective of the approach chosen, the classification differences between the applied methods were not significant (all P > 0.05), albeit approaches focusing on voxels with the highest uptake tended to perform superior. CONCLUSIONS: Irrespective of the analytical approach, F-FET PET is a robust tool for detection of late PsP with only minor differences between different analytical approaches. However, methodological standardization and harmonization are needed to ensure comparability between different centers.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tirosina/análogos & derivados , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Adulto Jovem
5.
J Agric Food Chem ; 67(32): 9039-9049, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31353898

RESUMO

This study focused on the effects of oxidized tyrosine products (OTPs) and major component dityrosine (DT) on the brain and behavior of growing mice. Male and female mice were treated with daily intragastric administration of either tyrosine (Tyr; 420 µg/kg body weight), DT (420 µg/kg body weight), or OTPs (1909 µg/kg body weight) for 35 days. We found that pure DT and OTPs caused redox state imbalance, elevated levels of inflammatory factors, hippocampal oxidative damage, and neurotransmitter disorders while activating the mitochondrial apoptosis pathway in the hippocampus and downregulating the genes associated with learning and memory. These events eventually led to growing mice learning and memory impairment, lagging responses, and anxiety-like behaviors. Furthermore, the male mice exhibited slightly more oxidative damage than the females. These findings imply that contemporary diets and food-processing strategies of the modern world should be modified to reduce oxidized protein intake.


Assuntos
Transtornos da Memória/etiologia , Aprendizagem Espacial , Tirosina/análogos & derivados , Tirosina/efeitos adversos , Tirosina/química , Animais , Comportamento Animal , Feminino , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Humanos , Masculino , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Estresse Oxidativo , Tirosina/metabolismo
6.
Lett Appl Microbiol ; 69(3): 181-189, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220356

RESUMO

Clovamide and its analogues are N-hydroxycinnamoyl-L-amino acids (HAA) that exhibit antioxidant activities. For environmental and economic reasons, biological synthesis of these plant-derived metabolites has garnered interest. In this study, we exploited HDT1, a BAHD acyltransferase recently isolated from red clover, for the production of clovamide and derivatives in S. cerevisiae and L. lactis. HDT1 catalyses the transfer of hydroxycinnamoyl-coenzyme A (CoA) onto aromatic amino acids. Therefore, by heterologously co-expressing HDT1 with 4-coumarate:CoA ligase (4CL), we succeeded in the biological production of clovamide and more than 20 other HAA, including halogenated ones, upon feeding the engineered micro-organisms with various combinations of cinnamates and amino acids. To the best of our knowledge, this is the first report on the biological synthesis of HAA and, more generally, on the synthesis of plant-derived antioxidant phenolic compounds in L. lactis. The production of these health beneficial metabolites in Generally Recognized As Safe (GRAS) micro-organisms such as S. cerevisiae and L. lactis provides new options for their delivery as therapeutics. SIGNIFICANCE AND IMPACT OF THE STUDY: N-hydroxycinnamoyl-L-amino acids such as clovamide are bioactive plant-derived phenolic compounds with health beneficial effects. Relying on chemical synthesis or direct extraction from plant sources for the supply of these valuable molecules poses challenges to environmental sustainability. As an alternative route, this work demonstrates the potential for biological synthesis of N-hydroxycinnamoyl-L-amino acids using engineered microbial hosts such as Saccharomyces cerevisiae and Lactococcus lactis. Besides being more eco-friendly, this approach should also provide more structurally diverse compounds and offer new methods for their delivery to the human body.


Assuntos
Lactococcus lactis/metabolismo , Saccharomyces cerevisiae/metabolismo , Tirosina/análogos & derivados , Aciltransferases/metabolismo , Antioxidantes , Humanos , Tirosina/biossíntese
7.
Mar Drugs ; 17(6)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31163697

RESUMO

Largazole, isolated from a marine Cyanobacterium of the genus Symploca, is a potent and selective Class I HDAC (histone deacetylation enzymes) inhibitor. This natural 16-membered macrocyclic depsipeptide features an interesting side chain unit, namely 3-hydroxy-7-mercaptohept-4-enoic acid, which occurs in many other natural sulfur-containing HDAC inhibitors. Notably, one similar fragment, where the amide moiety replaces the trans alkene moiety, appears in Psammaplin A, another marine natural product with potent HDAC inhibitory activities. Inspired by such a structural similarity, we hypothesized the fluoroolefin moiety would mimic both the alkene moiety in Largazole and the amide moiety in Psammaplin A, and thus designed and synthesized two novel fluoro olefin analogs of Largazole. The preliminary biological assays showed that the fluoro analogs possessed comparable Class I HDAC inhibitory effects, indicating that this kind of modification on the side chain of Largazole was tolerable.


Assuntos
Organismos Aquáticos/química , Cianobactérias/química , Depsipeptídeos/síntese química , Depsipeptídeos/farmacologia , Dissulfetos/química , Inibidores de Histona Desacetilases/farmacologia , Tiazóis/síntese química , Tiazóis/farmacologia , Tirosina/análogos & derivados , Alcenos/química , Depsipeptídeos/química , Ativação Enzimática/efeitos dos fármacos , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Histona Desacetilases/metabolismo , Tiazóis/química , Tirosina/química
8.
Science ; 364(6445)2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31196984

RESUMO

The human gut microbiota metabolizes the Parkinson's disease medication Levodopa (l-dopa), potentially reducing drug availability and causing side effects. However, the organisms, genes, and enzymes responsible for this activity in patients and their susceptibility to inhibition by host-targeted drugs are unknown. Here, we describe an interspecies pathway for gut bacterial l-dopa metabolism. Conversion of l-dopa to dopamine by a pyridoxal phosphate-dependent tyrosine decarboxylase from Enterococcus faecalis is followed by transformation of dopamine to m-tyramine by a molybdenum-dependent dehydroxylase from Eggerthella lenta These enzymes predict drug metabolism in complex human gut microbiotas. Although a drug that targets host aromatic amino acid decarboxylase does not prevent gut microbial l-dopa decarboxylation, we identified a compound that inhibits this activity in Parkinson's patient microbiotas and increases l-dopa bioavailability in mice.


Assuntos
Actinobacteria/enzimologia , Antiparkinsonianos/metabolismo , Proteínas de Bactérias/metabolismo , Enterococcus faecalis/enzimologia , Microbioma Gastrointestinal , Levodopa/metabolismo , Tirosina Descarboxilase/metabolismo , Tirosina/análogos & derivados , Actinobacteria/efeitos dos fármacos , Actinobacteria/genética , Animais , Antiparkinsonianos/administração & dosagem , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Descarboxilação/efeitos dos fármacos , Dopamina/metabolismo , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/genética , Microbioma Gastrointestinal/genética , Genoma Bacteriano , Células HeLa , Humanos , Levodopa/administração & dosagem , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Tirosina/administração & dosagem , Tirosina/química , Tirosina/farmacologia , Tirosina Descarboxilase/antagonistas & inibidores , Tirosina Descarboxilase/genética
9.
Clin Nucl Med ; 44(11): 864-869, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31205150

RESUMO

PURPOSE: Gliomas constitute the most frequent primary brain tumors. Glioblastoma, the most common and malignant glioma in adults, has dismal prognosis with any current therapy. On the other hand, low-grade gliomas, the second most common type of gliomas, are potentially curative with appropriate treatment. METHODS: We conducted a meta-analysis to assess the performance of PET tracers with the best available evidence, namely, fluorodeoxyglucose (FDG), C-methionine (MET), and F-fluoroethyltyrosine (FET), in differentiating low- from high-grade gliomas. RESULTS: Twenty-three studies with a total of 994 participants were included in this meta-analysis. The pooled sensitivities of both MET PET and FET PET were found to be significantly higher than of FDG PET (94%, 88%, and 63% respectively, P < 0.001). The pooled specificity of FDG PET was found to be significantly greater compared with both MET PET and FET PET (89%, 55%, and 57%, respectively; P = 0.002). Fluorodeoxyglucose PET was superior in terms of higher positive likelihood ratio values compared with both FET PET and MET PET. CONCLUSIONS: This meta-analysis indicated that both MET and FET were superior to FDG in terms of sensitivity for identifying glioma grade.


Assuntos
Neoplasias Encefálicas/patologia , Radioisótopos de Carbono , Fluordesoxiglucose F18 , Glioma/patologia , Metionina , Tomografia por Emissão de Pósitrons/métodos , Tirosina/análogos & derivados , Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Humanos , Gradação de Tumores
10.
Radiat Oncol ; 14(1): 89, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146757

RESUMO

BACKGROUND: Glioblastoma (GB) is the most common primary malignant brain tumor. Standard medical treatment consists of a maximal safe surgical resection, subsequently radiation therapy (RT) and chemotherapy with temozolomide (TMZ). An accurate definition of the tumor volume is of utmost importance for guiding RT. In this project we investigated the feasibility and treatment response of subvolume boosting to a PET-defined tumor part. METHOD: F98 GB cells inoculated in the rat brain were imaged using T2- and contrast-enhanced T1-weighted (T1w) MRI. A dose of 20 Gy (5 × 5 mm2) was delivered to the target volume delineated based on T1w MRI for three treatment groups. Two of those treatment groups received an additional radiation boost of 5 Gy (1 × 1 mm2) delivered to the region either with maximum [18F]FET or [18F]FAZA PET tracer uptake, respectively. All therapy groups received intraperitoneal (IP) injections of TMZ. Finally, a control group received no RT and only control IP injections. The average, minimum and maximum dose, as well as the D90-, D50- and D2- values were calculated for nine rats using both RT plans. To evaluate response to therapy, follow-up tumor volumes were delineated based on T1w MRI. RESULTS: When comparing the dose volume histograms, a significant difference was found exclusively between the D2-values. A significant difference in tumor growth was only found between active therapy and sham therapy respectively, while no significant differences were found when comparing the three treatment groups. CONCLUSION: In this study we showed the feasibility of PET guided subvolume boosting of F98 glioblastoma in rats. No evidence was found for a beneficial effect regarding tumor response. However, improvements for dose targeting in rodents and studies investigating new targeted drugs for GB treatment are mandatory.


Assuntos
Neoplasias Encefálicas/radioterapia , Modelos Animais de Doenças , Glioblastoma/radioterapia , Tomografia por Emissão de Pósitrons , Radioterapia Guiada por Imagem/métodos , Animais , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Estudos de Viabilidade , Feminino , Glioblastoma/metabolismo , Nitroimidazóis/metabolismo , Nitroimidazóis/uso terapêutico , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/uso terapêutico , Dosagem Radioterapêutica , Ratos Endogâmicos F344 , Resultado do Tratamento , Carga Tumoral , Tirosina/análogos & derivados , Tirosina/metabolismo , Tirosina/uso terapêutico
11.
Eur J Med Chem ; 176: 326-342, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31112893

RESUMO

Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis playing a central role in cardiovascular disease, obesity, and diabetes. These receptors show a high degree of stereoselectivity towards several classes of drugs. This review covers the most relevant findings that have been made in the last decade and takes into consideration only those compounds in which stereochemistry led to unexpected results or peculiar interactions with the receptors. These cases are reviewed and discussed with the aim to show how enantiomeric recognition originates at the molecular level. The structural characterization by crystallographic methods and docking experiments of complexes formed by PPARs with their ligands turns out to be an essential tool to explain receptor stereoselectivity.


Assuntos
Derivados de Benzeno/química , Derivados de Benzeno/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Acetatos/química , Acetatos/metabolismo , Animais , Sítios de Ligação , Cristalografia por Raios X , Humanos , Indóis/química , Indóis/metabolismo , Ligantes , Simulação de Acoplamento Molecular , Oxazóis/química , Oxazóis/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Receptores Ativados por Proliferador de Peroxissomo/antagonistas & inibidores , Receptores Ativados por Proliferador de Peroxissomo/química , Fenilpropionatos/química , Fenilpropionatos/metabolismo , Ligação Proteica , Estereoisomerismo , Relação Estrutura-Atividade , Tirosina/análogos & derivados , Tirosina/metabolismo
12.
Methods Mol Biol ; 1966: 261-289, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31041755

RESUMO

The chapter is focused on methods relevant for predictive toxicology and computer-aided drug design (adverse outcome pathway development, pharmacophore modeling, docking, and 3D QSAR analysis) and applied to study interactions between peroxisome proliferator-activated receptor γ (PPARγ) and its ligands. The methods have been combined to develop an integrated in silico approach allowing both to predict potential PPARγ-mediated hepatotoxicity of receptor's full agonists, thus supporting hazard characterization, and to identify naturally derived antidiabetic triterpenoids potentially acting through PPARγ partial agonism.


Assuntos
Hipoglicemiantes/farmacologia , Simulação de Acoplamento Molecular/métodos , PPAR gama/metabolismo , Humanos , Ligantes , Oxazóis/farmacologia , PPAR gama/agonistas , PPAR gama/química , Conformação Proteica , Relação Quantitativa Estrutura-Atividade , Rosiglitazona/farmacologia , Tirosina/análogos & derivados , Tirosina/farmacologia
13.
Medicina (Kaunas) ; 55(5)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126140

RESUMO

Background and objective: One of the reasons for thrombosis in chronic heart failure (CHF) might be reactive forms of oxygen activating platelets. The aim of this study was to evaluate the effect of oxidant hypochlorous acid (HOCl) on platelet aggregation and dityrosine concentration in CHF patients and healthy controls. Materials and Methods: CHF patients (n 67) and healthy (n 31) were investigated. Heart echoscopy, 6-min walking test, complete blood count, platelet aggregation, and dityrosine concentration were performed. Platelet aggregation and dityrosine concentration were measured in plasma samples after incubation with different HOCl concentrations (0.15, 0.0778, and 0.0389 mmol/L). Results: Platelet aggregation without oxidant was lower (p = 0.049) in CHF patients than in controls. The spontaneous platelet aggregation with oxidant added was higher in CHF patients (p = 0.004). Dityrosine concentration was also higher (p = 0.032) in CHF patients. Platelet aggregation was the highest in samples with the highest oxidant concentration in both healthy controls (p = 0.0006) and in CHF patients (p = 0.036). Platelet aggregation was higher in NYHA III group in comparison to NYHA II group (p = 0.0014). Concentration of dityrosine was significantly higher in CHF samples (p = 0.032). The highest concentration of dityrosine was obtained in NYHA IV group samples (p 0.05). Intensity of platelet aggregation, analyzed with ADP, was correlated with LV EF (r 0.42, p = 0.007). Dityrosine concentration was correlated with NYHA functional class (r 0.27, p 0.05). Conclusions: The increase in platelet aggregation in CHF and healthy controls shows the oxidant effect on platelets. The increase in dityrosine concentration in higher NYHA functional classes shows a higher oxidative stress in patients with worse condition.


Assuntos
Insuficiência Cardíaca/sangue , Ácido Hipocloroso/uso terapêutico , Agregação Plaquetária/fisiologia , Tirosina/análogos & derivados , Idoso , Feminino , Voluntários Saudáveis , Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Ácido Hipocloroso/farmacocinética , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Tirosina/análise , Tirosina/sangue
14.
J Physiol Pharmacol ; 70(1)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31019122

RESUMO

The influence of low-energy defibrillation on changes in the ET-1 levels in the myocardium and on disruptions in coronary blood flow and microcirculation being their consequence still remains unclear. Myocardial microcirculatory dysfunction is considered as a significant cause underlying myocardial dysfunction in post-cardiac arrest syndrome. This study is aimed at evaluating time-dependent changes in ET-1 levels in serum and the heart of a healthy rabbit following the application of a low-energy two-phase shock impulse. The research was conducted in 35 healthy rabbits at the age of 36 - 42 weeks and with body mass from 3200 to 4150 grams. The animals were divided in a randomized way into four groups depending on the dose of the electrical energy planned for the application during the experiment. The life parameters of the animals were monitored with the application of BeneView T5 patient monitor. The concentration of endothelin-1 in the groups was measured before, 15 and 360 minutes after the application of the low-energy double-phase straight-lined electrical impulse. A transthoracic low-energy defibrillation shock impulse causes a long-term increase in the endothelin-1 levels in the heart muscle and blood serum in a healthy rabbit. The increase in ET-1 levels results from the effect of electrical energy, independently of consequences of the ischemia/reperfusion injury. The increase in the endothelin-1 levels may lead to capillary blood flow abnormalities in the heart, contributing to the development of its dysfunction in the course of postresuscitation disease.


Assuntos
Estimulação Elétrica , Endotelina-1/metabolismo , Ventrículos do Coração/metabolismo , Miocárdio/metabolismo , Animais , Pressão Sanguínea , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Ventrículos do Coração/ultraestrutura , Masculino , Miocárdio/ultraestrutura , Coelhos , Tirosina/análogos & derivados , Tirosina/metabolismo , Função Ventricular
15.
Anticancer Res ; 39(3): 1383-1389, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842172

RESUMO

BACKGROUND/AIM: Our hypothesis was that rectus sheath block (RSB) analgesia could enhance satisfaction following midline laparotomy in patients with benign disease and cancer patients. PATIENTS AND METHODS: Initially, 56 patients were randomized into four groups; control group (n=12), single-dose (n=16), repeated-dose (n=12) and continuous infusion (n=16) RSB analgesia groups. The plasma concentrations of the NT marker were measured just before, immediately after and 24 h after operation. Patient satisfaction at 24 h postoperatively was filed on a 11-point numeric rating scale (SFS24; 0=fully unsatisfied; 10=fully satisfied). RESULTS: The RSB analgesia significantly enhanced the SFS24 scores in the study groups (p=0.001). The median plasma NT concentrations (pg/ml) following surgery (POP1) were significantly lower in patients with cancer versus patients with benign disease (5.3 vs. 7.6, p=0.008). Jitter plots of the individual SFS24 values versus plasma NT concentrations were significantly correlated in benign and cancer patients (r=-0.284, p=0.028). CONCLUSION: The RSB analgesia could significantly enhance patient satisfaction following midline laparotomy. Plasma NT concentrations versus patient satisfaction following surgery are significantly correlated in benign disease and cancer.


Assuntos
Neoplasias/cirurgia , Bloqueio Nervoso , Reto do Abdome , Tirosina/análogos & derivados , Idoso , Analgesia , Feminino , Humanos , Laparotomia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Estresse Nitrosativo , Tirosina/sangue
16.
J Immunoassay Immunochem ; 40(2): 123-138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30843753

RESUMO

In inflamed tissues, the reaction of nitric oxide and superoxide leads to the formation of an extremely reactive peroxynitrite (ONOO-), which is a well known oxidizing and nitrating agent that exhibits high reactivity at physiological pH. The peroxynitrite formed can attack a wide range of biomolecules via direct oxidative reactions or indirect radical-mediated mechanisms thus triggering cellular responses leading to cell signaling, oxidative injury, committing cells to necrosis or apoptosis. Cellular DNA is an important target for ONOO- attack, and can react with deoxyribose, nucleobases or induces single strand breaks. The free radical-mediated damage to proteins results in the modification of amino acid residues, cross-linking of side chains and fragmentation. Free/protein-bound tyrosines are attacked by various reactive nitrogen species (RNS), including peroxynitrite, to form free/protein-bound nitrotyrosine (NT). The formation of NT represents a specific peroxynitrite-mediated protein modification, and the detection of NT in proteins is considered as a biomarker for endogenous peroxynitrite activity. The peroxynitrite-driven oxidation and nitration of biomolecules may lead to autoimmunity and age-related neurodegenerative diseases. Hence, peroxynitrite modified DNA and nitrated proteins can act as neoantigens and lead to the generation of autoantibodies against self-components in autoimmune disorders.


Assuntos
Antígenos/imunologia , Autoanticorpos/imunologia , Autoimunidade , Ácido Peroxinitroso/imunologia , Reações Antígeno-Anticorpo , Biomarcadores/análise , DNA/efeitos dos fármacos , DNA/imunologia , Quebras de DNA , Humanos , Ácido Peroxinitroso/farmacologia , Tirosina/análogos & derivados , Tirosina/análise
17.
Nutrients ; 11(3)2019 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-30884817

RESUMO

Mg2+ deficiency may be involved in lifestyle-related diseases, including hypertension, cardiovascular diseases, and diabetes mellitus. Dietary Mg2+ is absorbed in the intestine mediated through transcellular and paracellular pathways. However, there is little research into what factors upregulate Mg2+ absorption. We searched for food constituents that can increase the expression levels of Mg2+ transport carriers using mouse colonic epithelial MCE301 cells. Cyanidin, an anthocyanidin found in black beans and berries, increased the mRNA levels of Mg2+ transport carriers including transient receptor potential melastatin 6 (TRPM6) channel and cyclin M4 (CNNM4). The cyanidin-induced elevation of Mg2+ transport carriers was blocked by GW6471, a peroxisome proliferator-activated receptor α (PPARα) inhibitor, but not by PPARγ, PPARδ, and protein kinase A inhibitors. Cyanidin-3-glucoside showed similar results to cyanidin. Cyanidin increased the protein levels of TRPM6 and CNNM4, which were distributed in the apical and lateral membranes, respectively. The nuclear localization of PPARα and reporter activities of Mg2+ transport carriers were increased by cyanidin, which were inhibited by GW6471. The cyanidin-induced elevation of reporter activity was suppressed by a mutation in a PPAR-response element. Fluorescence measurements using KMG-20, an Mg2+ indicator, showed that Mg2+ influx and efflux from the cells were enhanced by cyanidin, and which were inhibited by GW6471. Furthermore, cyanidin increased paracellular Mg2+ flux without affecting transepithelial electrical resistance. We suggest that cyanidin increases intestinal Mg2+ absorption mediated by the elevation of TRPM6 and CNNM4 expression, and may constitute a phytochemical that can improve Mg2+ deficiency.


Assuntos
Antocianinas/farmacologia , Proteínas de Transporte de Cátions/efeitos dos fármacos , Magnésio/metabolismo , PPAR alfa/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Animais , Linhagem Celular , Colo/citologia , Células Epiteliais/metabolismo , Glucosídeos/farmacologia , Mucosa Intestinal/citologia , Deficiência de Magnésio/metabolismo , Camundongos , Oxazóis/metabolismo , RNA Mensageiro/metabolismo , Canais de Cátion TRPM/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Regulação para Cima
18.
Nitric Oxide ; 87: 23-30, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30849493

RESUMO

Amyloid formation of human islet amyloid polypeptide (hIAPP) is one of the most common pathological features of type 2 diabetes (T2D). Increasing evidences have shown that the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) play an important role in the development of the T2D. Interestingly, our previous studies indicated that heme could bind to hIAPP, and the complex might induce the nitration of tyrosine residue (Y37) of hIAPP in the presence of hydrogen peroxide and nitrite. However, it remains unclear about effect of the nitration on the implicated function of hIAPP in the development of T2D. In this study, fluorescent assays, transmission electron microscopy (TEM), atomic force microscope (AFM) were used to demonstrate that nitration of hIAPP significantly decreased its fibril formation. But the decreased fibril formation was not through the diminished aggregation of hIAPP monomer as suggested by the results of circular dichroism spectroscopy (CD) and gel electrophoresis assay. Surface-enhanced raman spectroscopy (SERS) indicated that nitration of hIAPP impaired the intermolecular hydrogen bonding. On the basis of these results, we hypothesize that nitration of hIAPP may block the intermolecular hydrogen bonding, leading to the inhibition of its fibril formation. In addition, cytotoxicity study of native and modified hIAPP was also performed on INS-1 cells, which revealed exacerbated toxicity of hIAPP by its nitration. The findings in this study that nitration of hIAPP promotes its oligomer formation and thus exacerbates its cytotoxicity suggests a possible link between the nitrite (or the sum of nitrite and nitrate) levels and T2D, and ameliorated nitration of hIAPP by diminishing nitrative stress might be a promising therapeutic strategy for T2D.


Assuntos
Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Processamento de Proteína Pós-Traducional , Animais , Linhagem Celular Tumoral , Heme/metabolismo , Peróxido de Hidrogênio/química , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Polipeptídeo Amiloide das Ilhotas Pancreáticas/toxicidade , Nitritos/química , Ligação Proteica , Multimerização Proteica , Ratos , Tirosina/análogos & derivados , Tirosina/química
19.
Mar Drugs ; 17(2)2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30813373

RESUMO

Sponges are a valuable source of natural compounds and biomaterials for many biotechnological applications. Marine sponges belonging to the order Verongiida are known to contain both chitin and biologically active bromotyrosines. Aplysina archeri (Aplysineidae: Verongiida) is well known to contain bromotyrosines with relevant bioactivity against human and animal diseases. The aim of this study was to develop an express method for the production of naturally prefabricated 3D chitin and bromotyrosine-containing extracts simultaneously. This new method is based on microwave irradiation (MWI) together with stepwise treatment using 1% sodium hydroxide, 20% acetic acid, and 30% hydrogen peroxide. This approach, which takes up to 1 h, made it possible to isolate chitin from the tube-like skeleton of A. archeri and to demonstrate the presence of this biopolymer in this sponge for the first time. Additionally, this procedure does not deacetylate chitin to chitosan and enables the recovery of ready-to-use 3D chitin scaffolds without destruction of the unique tube-like fibrous interconnected structure of the isolated biomaterial. Furthermore, these mechanically stressed fibers still have the capacity for saturation with water, methylene blue dye, crude oil, and blood, which is necessary for the application of such renewable 3D chitinous centimeter-sized scaffolds in diverse technological and biomedical fields.


Assuntos
Quitina/isolamento & purificação , Poríferos/química , Animais , Materiais Biocompatíveis/análise , Materiais Biocompatíveis/química , Materiais Biocompatíveis/isolamento & purificação , Quitina/análise , Quitina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Tirosina/análogos & derivados , Tirosina/análise , Tirosina/química , Tirosina/isolamento & purificação
20.
Ann Nucl Med ; 33(6): 394-403, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30820863

RESUMO

OBJECTIVE: L-type amino acid transporter 1 (LAT1) is strongly expressed on the cell membrane in various types of human cancer cells, while being minimally expressed in normal or inflammatory tissues. Therefore, LAT1-targeting PET tracers have been developed for cancer-specific imaging. The purpose of this study was to study the distribution of two LAT1-targeting PET tracers, L-4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) and L-3-18F-alpha-methyl tyrosine (18F-FAMT), in relation to the tumor blood flow, using rat xenograft models. METHODS: Rat tumor xenograft models of C6 glioma (n = 4; tumors = 8) and MIA PaCa-2 (pancreatic cancer) (n = 4; tumors = 6) were used. The expressions of LAT1 and CD98hc were evaluated by both immunofluorescence staining and western blot analysis. Dynamic PET was performed after injection of 18F-FAMT or 18F-FBPA (scan duration = 70 min) following 15O-water PET (scan duration = 10 min). The PET data were subjected to kinetic analyses, and the K1, k2, and total distribution volume (Vt) were calculated using the one-tissue compartment model. The accumulation of the LAT1 tracers was expressed in terms of their Vt. Tumor blood flow (TBF) was represented by the K1 value in 15O-water PET. RESULTS: LAT1/CD98hc expression was confirmed in both xenografts by immunofluorescence staining. Western blot analysis showed higher functional expression of LAT1 in the C6 glioma cells as compared to the MIA PaCa-2 cells (C6 glioma/MIA PaCa-2 relative expression ratio = 1.70). The Vt values of both 18F-FBPA and 18F-FAMT were significantly higher in the C6 glioma xenografts than in the MIA PaCa-2 xenografts (C6 glioma: 2.27 ± 0.35 and 2.03 ± 0.23, respectively; MIA PaCa-2: 1.28 ± 0.26 and 1.35 ± 0.15, respectively). Meanwhile, there was no significant correlation of the Vt value of either 18F-FBPA or 18F-FAMT with the TBF, in either the C6 glioma or the MIA PaCa-2 xenografts. CONCLUSIONS: This study revealed that total distribution volumes of the LAT1-targeting PET tracers 18F-FBPA and 18F-FAMT were independent of the tumor blood flow and might reflect the functional expression levels of LAT1 in the C6 glioma and MIA PaCa-2 xenograft models.


Assuntos
Circulação Sanguínea , Transformação Celular Neoplásica , Glioma/patologia , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Animais , Compostos de Boro/metabolismo , Compostos de Boro/farmacocinética , Linhagem Celular Tumoral , Glioma/irrigação sanguínea , Glioma/diagnóstico por imagem , Glioma/metabolismo , Humanos , Masculino , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/metabolismo , Fenilalanina/análogos & derivados , Fenilalanina/metabolismo , Fenilalanina/farmacocinética , Traçadores Radioativos , Compostos Radiofarmacêuticos/metabolismo , Ratos , Distribuição Tecidual , Tirosina/análogos & derivados , Tirosina/metabolismo , Tirosina/farmacocinética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA