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1.
Artigo em Inglês | MEDLINE | ID: mdl-38083486

RESUMO

The development of high-density multielectrode catheters has significantly advanced cardiac electrophysiology mapping. High-density grid catheters have enabled the creation of a novel technique for reconstructing electrogram (EGM) signals known as "omnipole," which is believed to be more reliable than other methods, especially in terms of orientation independence. This study aims to evaluate how distance affects the omnipolar reconstruction of EGMs by comparing different configurations. Using an animal set up of perfused isolated rabbit hearts, recordings were taken using an ad hoc high-density epicardial multielectrode catheter. Inter-electrode distances ranging from 1 to 4 mm were analysed for their effect on the quality of resulting EGMs. Two biomarkers were computed to evaluate the robustness of the reconstructions: the areas contained within the bipolar loops and the amplitudes of the omnipoles. We hypothesised that both bipolar and omnipolar electrograms would be more robust at shorter inter-electrode distances. The results showed that an increase in distance triggers an increase in loop areas and amplitudes, which supports the hypothesis. This finding provides a more reliable estimate of wavefront propagation for the cross-omnipolar reconstruction method. These results emphasise the importance of distance in cardiac electrophysiology mapping and provide valuable insights into the use of high-density multielectrode catheters for EGM reconstruction.Clinical Relevance- The results of this study have direct clinical relevance in the application of the described techniques to recording systems in the cardiac electrophysiology laboratory, enabling clinicians to obtain more precise characterisation of signals in the myocardium.


Assuntos
Técnicas Eletrofisiológicas Cardíacas , Miocárdio , Animais , Coelhos , Técnicas Eletrofisiológicas Cardíacas/métodos , Eletrodos , Eletrofisiologia Cardíaca , Pericárdio
2.
Cell Mol Neurobiol ; 42(5): 1501-1512, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33492599

RESUMO

One of the most frequent neurological disorders in children is febrile seizures (FS), a risk for epilepsy in adults. Glutamate is the main excitatory neurotransmitter in CNS acting through ionotropic and metabotropic receptors. Excess of glutamate in the extracellular space elicits excitotoxicity and has been associated with neurological disorders, such as epilepsy. The removal of extracellular glutamate by excitatory amino acid transporters (EATT) plays an important neuroprotective role. GLT-1 is the main EAAT present in the cortex brain. On the other hand, an increase in metabotropic glutamate receptors 5 (mGlu5R) levels or their overstimulation have been related to the appearance of seizure events in different animal models and in temporal lobe epilepsy in humans. In this work, the status of several components of the glutamatergic system has been analysed in the cortex brain from an FS rat model at short (48 h) and long (20 days) term after hyperthermia-induced seizures. At the short term, we detected increased GLT-1 levels, reduced glutamate concentration, and unchanged mGlu5R levels, without neuronal loss. However, at the long term, an increase in mGlu5R levels together with a decrease in both GLT-1 and glutamate levels were observed. These changes were associated with the appearance of an anxious phenotype. These results suggest a neuroprotective role of the glutamatergic components mGlu5R and GLT-1 at the short term. However, this neuroprotective effect seems to be lost at the long term, leading to an anxious phenotype and suggesting an increased vulnerability and propensity to epileptic events in adults.


Assuntos
Epilepsia , Hipertermia Induzida , Convulsões Febris , Animais , Encéfalo/metabolismo , Epilepsia/genética , Ácido Glutâmico/metabolismo , Ratos
3.
Rev. Fac. Odontol. (B.Aires) ; 37(85): 7-14, 2022. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1397370

RESUMO

La amelogénesis imperfecta (AI) es un grupo de tras-tornos hereditarios, clínica y etiológicamente hete-rogéneos, derivados de mutaciones genéticas, que se caracterizan por anomalías cualitativas y cuanti-tativas del desarrollo del esmalte, pudiendo afectar la dentición primaria y/o permanente. El tratamiento del paciente con AI es complejo y multidiscliplinario; supone un desafío para el odontólogo, ya que por lo general están involucradas todas las piezas dentarias y afecta no solo la salud buco dental sino el aspecto emocional y psicológico de los pacientes. Con el obje-tivo de describir el tratamiento integral y rehabilita-dor realizado en una paciente con diagnóstico de AI tipo III, se reporta el caso de un adolescente de sexo femenino de 13 años, que concurrió en demanda de atención a la Cátedra de Odontología Integral Niños de la Facultad de Odontología de la Universidad de Buenos Aires (FOUBA), cuyo motivo de consulta fue la apariencia estética y la hipersensibilidad de sus pie-zas dentarias. Durante el examen clínico intraoral, se observó que todas las piezas dentarias presentaban un esmalte rugoso, blando, con irregularidades y una coloración amarronada, compatible con diagnóstico de Amelogénesis Imperfecta tipo III hipomineralizada. Conclusión: El tratamiento rehabilitador de la AI en los pacientes en crecimiento y desarrollo estará diri-gido a intervenir de manera integral y temprana para resolver la apariencia estética y funcional, evitar las repercusiones sociales y emocionales, y acompañar a los pacientes y sus familias (AU)


Amelogenesis imperfecta (AI) is a group of clinically and etiologically heterogeneous hereditary disorders, derived from genetic mutations, characterized by qualitative and quantitative anomalies of enamel development, which can affect primary and/or permanent dentition. The treatment of patients with AI is complex and multidisciplinary, it is a challenge for the dentist, since in general all the teeth are involved and it affects not only oral health but also the emotional and psychological aspect of the patients. Objective: To describe the comprehensive and rehabilitative treatment carried out in an adolescent patient with a diagnosis of type III AI. Case report: The case of a 13-year-old female patient, who required dental attention at the Department of Dentistry for Children of the School of Dentistry of the University of Buenos Aires, whose reason for consultation was esthetic appearance and hypersensitivity of her teeth. In the intraoral clinical examination, it was observed that all the teeth had rough, soft enamel, with irregularities and a brownish color, compatible with the diagnosis of type III hypomineralized Amelogenesis Imperfecta. Conclusion: Rehabilitative treatment of AI in growing and developing patients will be aimed at early and comprehensive intervention to resolve esthetic and functional appearance, avoid social and emotional repercussions and accompany patients and their families (AU)


Assuntos
Humanos , Feminino , Adolescente , Assistência Odontológica para Crianças , Coroas , Amelogênese Imperfeita/terapia , Equipe de Assistência ao Paciente , Faculdades de Odontologia , Preparo da Cavidade Dentária/métodos , Esmalte Dentário/patologia , Hipoplasia do Esmalte Dentário/etiologia , Restauração Dentária Permanente/métodos , Estética Dentária , Amelogênese Imperfeita/classificação
4.
Artigo em Inglês | MEDLINE | ID: mdl-32145667

RESUMO

Cognitive decline is one of the hallmarks of aging and can vary from mild cognitive impairment to dementia to Alzheimer's disease. In addition to some lifestyle interventions, there is room for the use of nutraceuticals/functional foods as pharma-nutritional tools to lessen the burden of cognitive decline before it worsens. We previously reported the promising molecular actions of milk fat globule membranes and krill oil concentrates in a rat model of aging. In this study, we concentrated on the activities on cognition, using an array of validated tests. We also performed lipidomic analyses of plasma, erythrocytes, and different brain areas. We report lower emotional memory (contextual fear conditioning) in aged rats supplemented with concentrates of polar lipids from buttermilk or krill oil at doses that approximate human consumption. No other behavioral parameter was significantly influenced by the supplements, calling for further research to confirm or not the purported salubrious activities of polar lipids, namely those rich in ω3 long-chain polyunsaturated fatty acids, on cognitive decline.


Assuntos
Leitelho , Cognição/efeitos dos fármacos , Disfunção Cognitiva/dietoterapia , Suplementos Nutricionais , Euphausiacea/química , Ácidos Graxos Ômega-3/administração & dosagem , Envelhecimento , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Disfunção Cognitiva/sangue , Modelos Animais de Doenças , Teste de Labirinto em Cruz Elevado , Ácidos Graxos Ômega-3/sangue , Masculino , Memória/efeitos dos fármacos , Ratos , Ratos Wistar , Memória Espacial/efeitos dos fármacos
5.
Clin Transl Oncol ; 21(4): 489-498, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30293230

RESUMO

PURPOSE: Breast cancer patients receiving hormonal therapies face risks of relapse, increased rates of cardiovascular events, and toxicities of therapy such as aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS). C-reactive protein (CRP), a marker for inflammation, is associated with breast cancer outcomes. We evaluated whether the olive-derived polyphenol hydroxytyrosol combined with omega-3 fatty acids and curcumin would reduce CRP and musculoskeletal symptoms in breast cancer patients receiving adjuvant hormonal therapies. EXPERIMENTAL DESIGN: This prospective, multicenter, open-label, single arm, clinical trial enrolled post-menopausal breast cancer patients (n = 45) with elevated C-reactive protein (CRP) taking predominantly aromatase inhibitors to receive a combination of hydroxytyrosol, omega-3 fatty acids, and curcumin for 1 month. CRP, other inflammation-associated cytokines, and pain scores on the Brief Pain Inventory were measured before therapy, at the end of therapy and 1 month after completion of therapy. RESULTS: CRP levels declined during the therapy [from 8.2 ± 6.4 mg/L at baseline to 5.3 ± 3.2 mg/L (p = 0.014) at 30 days of treatment], and remained decreased during the additional 1 month off therapy. Subjects with the highest baseline CRP levels had the greatest decrease with the therapy. Pain scores also decreased during the therapy. There were no significant adverse events. CONCLUSIONS: The combination of hydroxytyrosol, omega-3 fatty acids, and curcumin reduced inflammation as indicated by a reduction in CRP and reduced pain in patients with aromatase-induced musculoskeletal symptoms. Longer studies comparing this combination to other anti-inflammatories in larger groups of patients with clinical outcome endpoints are warranted.


Assuntos
Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Curcumina/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Inflamação/tratamento farmacológico , Dor Musculoesquelética/tratamento farmacológico , Álcool Feniletílico/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/patologia , Proteína C-Reativa/metabolismo , Quimioterapia Adjuvante/efeitos adversos , Curcumina/efeitos adversos , Combinação de Medicamentos , Ácidos Graxos Ômega-3/efeitos adversos , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Pessoa de Meia-Idade , Dor Musculoesquelética/induzido quimicamente , Dor Musculoesquelética/patologia , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/efeitos adversos , Projetos Piloto , Pós-Menopausa , Estudos Prospectivos
6.
Rev. Fac. Odontol. (B.Aires) ; 34(76): 37-42, 2019. ilus, tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1102537

RESUMO

Los objetivos de este trabajo fueron conocer la percepción de estudiantes y docentes sobre la implementación de la modalidad de clases expositivas on-line, estimar la frecuencia y oportunidad de acceso por parte de los alumnos y comparar los resultados obtenidos en las calificaciones finales obtenidas con la modalidad teórico presencial y la on-line. El recurso resultó positivo para el 80,62% y 73,33% de alumnos y docentes respectivamente. Los primeros ingresaron cada uno un promedio de 2,75±1,45 veces a cada uno de los 15 módulos y el 60.45% lo hizo 15 días antes del examen. No hubo diferencias entre las calificaciones obtenidas entre dos cohortes que utilizaron las diferentes modalidades. Se concluyó que la modalidad on-line con clase de repaso presencial fue percibida como apropiada y con contenidos relevantes. Fue utilizada por los estudiantes como una herramienta de consulta, con amplia flexibilidad horaria y en reiteradas oportunidades, sin restarle horas a la atención de pacientes (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Estudantes de Odontologia , Odontopediatria/educação , Aula , Educação a Distância , Argentina , Faculdades de Odontologia , Epidemiologia Descritiva , Estudos Transversais , Estudos Prospectivos , Tecnologia da Informação
8.
Food Chem Toxicol ; 107(Pt A): 329-338, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28689060

RESUMO

BACKGROUND AND AIMS: Hydroxytyrosol (HT) is the primary phenolic compound of olives, virgin olive oil, and their byproducts. Proteomic analysis of metabolically active tissues helps elucidating novel mechanisms of action and potential targets in cardiometabolic disease. Thus, we aimed at determining the impact of long-term HT supplementation on the proteome of adipose and liver tissue, in mice. METHODS: C57BL/6J mice received either a control diet or a diet supplemented with nutritionally relevant doses of HT for eight weeks. RESULTS: HT supplementation differentially affects the adipose and liver tissues proteome, as evaluated by super-SILAC. Some oxidative stress-related proteins were modulated in both tissues, such as the multifunctional protein peroxiredoxin 1, which was consistently repressed by HT supplementation. In some cases tissue-dependent modulation was observed, as in the case of FASN. CONCLUSIONS: This study provides interesting information on the connection between changes seen at tissue proteome level and the metabolic effects of HT. The use of this pertinent proteomics quantification approach may prove quite useful for uncovering novel potential pharmaco-nutritional targets of HT supplementation.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Suplementos Nutricionais/análise , Fígado/efeitos dos fármacos , Fígado/metabolismo , Álcool Feniletílico/análogos & derivados , Tecido Adiposo/química , Animais , Fígado/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/farmacologia , Proteínas/genética , Proteínas/metabolismo , Proteômica
9.
Food Chem ; 224: 219-223, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28159259

RESUMO

Resveratrol is a stilbene, which is one of a group of polyphenols in many plant foods. Interest in this substance lies in its potential health benefits. This study aimed to compare two different methods, chromatographic and constant-wavelength synchronous spectrofluorimetry, an alternative technique to determine the amount of resveratrol dietary supplements, as a model for more complex foods. High-performance liquid chromatography-photodyode array detector-mass spectrometry/mass spectrometry was used to confirm the results. The results obtained showed that both methods were valid for the determination of resveratrol in dietary supplements. HPLC with fluorescence and variable wavelength detectors offered better linearity and sensitivity, and would be more suitable for the determination of several stilbenes in complex samples. On the other hand, constant-wavelength synchronous spectrofluorimetry is a sensitive, rapid and inexpensive method that could be used for quick and precise determination when samples are expected to contain only one stilbene.


Assuntos
Suplementos Nutricionais/análise , Estilbenos/análise , Verduras/química , Cromatografia Líquida de Alta Pressão/métodos , Resveratrol , Espectrometria de Massas em Tandem/métodos
10.
Curr Pharm Des ; 23(7): 983-988, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27748191

RESUMO

Some epidemiological studies suggest that increased consumption of anthocyanins is associated with lower risk of cardiovascular disease (CVD) and hypertension. Also, high consumption of anthocyanin-rich fruit, such as berries, is associated with a lower risk of developing type 2 diabetes (T2D). In this review, we briefly yet critically assess the available evidence in support of an anti-diabetic role of anthocyanins derived from berries, especially bilberry (Vaccinium myrtillus L., also known as European blueberry, whortleberry, huckleberry and blaeberry) and blueberry (Vaccinium corymbosum, native to the United States). Further, cellular and molecular mechanisms are discussed and the "pharma-nutrition" use of anthocyanin-based preparations for the prevention and treatment of T2D is examined. We conclude that animal and in vitro studies strongly indicate that bilberry and blueberry have the potential to ameliorate T2D and its cardio-metabolic outcomes. However, appropriate clinical trials are lacking and will eventually clarify whether these foods (either as such or formulated as nutraceuticals) might be added to the current pharma-nutritional armamentarium.


Assuntos
Antocianinas/uso terapêutico , Mirtilos Azuis (Planta)/química , Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vaccinium myrtillus/química , Animais , Antocianinas/química , Antocianinas/isolamento & purificação , Sistema Cardiovascular/metabolismo , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
11.
Expert Rev Respir Med ; 10(9): 1023-33, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27176208

RESUMO

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a respiratory problem with the highest prevalence and strongest socio-economic impact in the world and whose morbimortality keeps increasing. Treating this disease is a challenge in the field of pneumology since the market now offers a wide range of bronchodilators. Tiotropium bromide, a long-acting anticholinergic bronchodilator, is a drug used to deal with this pathology. AREAS COVERED: The UPLIFT study was a 4-year (2004-2008) clinical multi-center trial in which tiotropium bromide was compared with a placebo. We present a bibliographic resume covering the multiple sub-analyses published since the end of the clinical trial, between 2009-2015. These sub-analyses analyzed the results obtained in UPLIFT in parallel, provided additional data about safety profiles, exacerbations, hospitalization and mortality rates, and lung function, among others. Expert Commentary: Tiotropium bromide is a significant advance for the maintenance treatment of patients with COPD. The favorable results obtained leave the door open to the possibility of improving the natural history of COPD and confirmed tiotropium bromide as the gold standard drug as monotherapy for treatment of COPD.


Assuntos
Broncodilatadores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/uso terapêutico , Hospitalização , Humanos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
12.
J Pediatr Gastroenterol Nutr ; 56(6): 657-62, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23403437

RESUMO

OBJECTIVE: The aim of the present study was to explore the relation between lung function and serum retinol (SR) in cystic fibrosis (CF) patients. METHODS: This was a cross-sectional study conducted in a group of 98 young patients with CF (6.8-22.3 years), after the exclusion of those with pulmonary exacerbation, vitamin A deficiency, or other risks, from an initial group of 124 cases. RESULTS: Data of forced expiratory volume in 1 second (FEV1) were widely scattered (87.7% ± 16.9%). These were similar in the 78 pancreatic insufficient and 11 pancreatic sufficient patients. SR (56.6 ± 18.4 µg/dL) was >2.5th percentile of healthy people in the whole group, although 31 patients were situated above the 97.5th percentile (higher value: 110 µg/dL). The FEV1 was noticeably higher in these than in those within the normal range (93.6 ± 14.0 vs 85.0 ± 17.6 µg/dL; P < 0.05). The z score of SR correlated positively with FEV1 (r = 0.364; P = 0.000), after adjusting data for sex, age, body mass index, and pancreatic function. The odds ratio for a FEV1 >80% is 3.78 in patients with SR above the 97.5th percentile, versus only 0.26 in those within the normal range. There were no cases with retinol toxicity. CONCLUSIONS: FEV1 of young patients with CF correlates positively with SR, regardless of age, pancreatic function, or nutritional condition. Those with a moderately high retinol (up to 110 µg/dL) maintain the best respiratory function (FEV1 ≥80% in >90% of them) without any signs of toxicity.


Assuntos
Fibrose Cística/sangue , Fibrose Cística/fisiopatologia , Pulmão/fisiopatologia , Regulação para Cima , Vitamina A/sangue , Adolescente , Adulto , Antioxidantes/efeitos adversos , Antioxidantes/análise , Antioxidantes/uso terapêutico , Índice de Massa Corporal , Criança , Estudos de Coortes , Estudos Transversais , Fibrose Cística/dietoterapia , Suplementos Nutricionais/efeitos adversos , Insuficiência Pancreática Exócrina/etiologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Razão de Chances , Estresse Oxidativo , Estudos Prospectivos , Magreza/etiologia , Vitamina A/efeitos adversos , Vitamina A/uso terapêutico , Adulto Jovem
13.
Rev. cuba. plantas med ; 14(2)abr.-jun. 2009.
Artigo em Espanhol | CUMED | ID: cum-42637

RESUMO

En muchos países la exposición accidental o voluntaria a sustancias tóxicas es causa frecuente de procesos patológicos agudos y crónicos, que constituyen la segunda causa de muerte, después de las enfermedades infecciosas. En reportes estadísticos predominan las intoxicaciones por psicofármacos y plaguicidas, pero existen otras como las provocadas por sustancias vegetales que también son consultas frecuentes en los servicios de urgencias(AU)


In many countries, the accidental or intentional exposure to toxic substances is the frequent cause of acute and chronic pathological processes that represent the second cause of death after the infectious illnesses. In statistical reports, poisoning from pscyho drugs and herbicides prevail, but there are others as those caused by vegetable substances that are also commonly treated in the emergency services(AU)


Assuntos
Datura stramonium/toxicidade , Plantas Tóxicas/toxicidade
14.
Rev. cuba. plantas med ; 14(2)abr.-jun. 2009. tab
Artigo em Espanhol | LILACS | ID: lil-575617

RESUMO

En muchos países la exposición accidental o voluntaria a sustancias tóxicas es causa frecuente de procesos patológicos agudos y crónicos, que constituyen la segunda causa de muerte, después de las enfermedades infecciosas. En reportes estadísticos predominan las intoxicaciones por psicofármacos y plaguicidas, pero existen otras como las provocadas por sustancias vegetales que también son consultas frecuentes en los servicios de urgencias...


In many countries, the accidental or intentional exposure to toxic substances is the frequent cause of acute and chronic pathological processes that represent the second cause of death after the infectious illnesses. In statistical reports, poisoning from pscyho drugs and herbicides prevail, but there are others as those caused by vegetable substances that are also commonly treated in the emergency services...


Assuntos
Datura stramonium/toxicidade , Plantas Tóxicas/toxicidade
15.
Bull Environ Contam Toxicol ; 82(2): 158-61, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18654728

RESUMO

Samples of seaweed which are used for human consumption were collected along the Galician coast (NW Spain), in order to determine the level of contamination from polycyclic aromatic hydrocarbons, by supercritical fluid extraction and liquid chromatographic analysis. No detection was made of benzo[a]pyrene, benzo[a]anthracene, benzo[b]fluoranthene, benzo[ghi]perylene and dibenzo[ah]anthracene. PAHs were found and quantified in only two samples. The PAHs found were the following: anthracene, chrysene, fluoranthene, fluorene and pyrene. The levels found were below maximum limits established by the Spanish Food Safety authority (<200 mg/kg dry weight). Here we show that no relevant effects were detected in terms of PAHs contamination in seaweed.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Petróleo , Compostos Policíclicos/isolamento & purificação , Alga Marinha/química , Poluentes Químicos da Água/isolamento & purificação , Acidentes , Cromatografia Líquida de Alta Pressão , Padrões de Referência
16.
Eur J Neurosci ; 14(3): 483-94, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11553298

RESUMO

Known effects of neurotrophins in the developing central nervous system include induction or regulation of peptide expression. Hypothalamic postmitotic thyrotropin-releasing hormone (TRH)-producing neurons may require neurotrophins for survival and/or differentiation. This issue was investigated using primary cell cultures derived from 17-day-old fetal rat hypothalamus seeded in serum-free medium and analysed up to 4 days in vitro culture. Neurotrophin receptor (TrkB and TrkC) mRNA expression was detected by RT-PCR in fetal hypothalamus and throughout the culture period. Western blots confirmed the expression of the full-length proteins in vitro. Semi-quantitative RT-PCR showed that the addition of brain-derived neurotrophic factor (BDNF) increases TRH mRNA levels while the addition of neurotrophin-3 does not. TRH cell content was not modified. Studies on the effect of cell density or homologous conditioned medium demonstrated that endogenous factors probably contribute to determine TRH mRNA levels. One of these factors was BDNF because basal TRH mRNA levels were reduced by the addition of a Trk inhibitor or anti-BDNF. TrkB mRNA was expressed in 27% of cells and TRH mRNA in 2% of cells. The number of TRH+ cells was not affected by BDNF treatment. Forty-eight per cent of TRH neurons contained TrkB mRNA; these neurons had higher amounts of TRH mRNA than TrkB- neurons. Only TrkB+ cells responded to BDNF by increasing their TRH mRNA levels suggesting that BDNF may directly affect TRH biosynthesis. In conclusion, fetal hypothalamic TRH neurons are probably heterogeneous in regard to the neurotrophic factors enhancing peptide and mRNA levels. BDNF enhances TRH mRNA levels in a population of TrkB+ fetal hypothalamic TRHergic neurons in primary culture. However, additional influences may be necessary for the establishment of peptide phenotype in the TrkB+ neurons.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/farmacologia , Hipotálamo/metabolismo , Neurônios/metabolismo , RNA Mensageiro/biossíntese , Receptor trkB/metabolismo , Hormônio Liberador de Tireotropina/biossíntese , Animais , Western Blotting , Contagem de Células , Células Cultivadas , Meios de Cultivo Condicionados , Digoxigenina , Hipotálamo/citologia , Hipotálamo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Testes de Precipitina , Radioimunoensaio , Ratos , Ratos Wistar , Receptor trkB/genética , Receptor trkC/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Microsc Res Tech ; 54(3): 173-87, 2001 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-11458400

RESUMO

Adrenomedullin (AM) is a novel neuropeptide with special significance in the mammalian hypothalamo-hypophysial axis. By using an antiserum specific for human AM, we have studied the localization of AM-like immunoreactive (AMi) cell bodies and fibers in the hypothalamus and hypophysis of the amphibians Rana perezi (anuran), Pleurodeles waltl (urodele), and Dermophis mexicanus (gymnophionan). Distinct AMi cell groups were found for each species. In the anuran, six cell groups were localized in the preoptic and infundibular regions, whereas only three and one were found in the urodele and gymnophionan, respectively. A comparative analysis of AMi cells and cells expressing arginine vasotocin (AVT), neuropeptide Y (NPY), and tyrosine hydroxylase (TH) revealed strong differences between species. Thus, colocalization of AVT/AM is most likely to occur in the preoptic magnocellular nucleus of urodeles and it is reflected by the intense AM immunoreactivity in the neural lobe of the hypophysis. Colocalization of NPY/AM seems to be possible in the suprachiasmatic nucleus of anurans. In the gymnophionan, cells containing AVT and NPY are distinct from AMi cells. Only in anurans, the ventral aspect of the suprachiasmatic nucleus possesses a small population of AMi cells that express also TH immunoreactivity and most likely also express NPY. The results strongly suggest that AM in amphibians plays an important regulatory role in the hypothalamo-hypophysial system, as has been demonstrated in mammals. On the other hand, substantial differences have been found between species with respect to the degree of colocalization with other chemical substances.


Assuntos
Anfíbios/metabolismo , Hipotálamo/metabolismo , Peptídeos/metabolismo , Adrenomedulina , Animais , Hipotálamo/anatomia & histologia , Hipotálamo/citologia , Imuno-Histoquímica , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Ranidae/metabolismo , Salamandridae/metabolismo
18.
Br J Pharmacol ; 132(2): 547-55, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11159705

RESUMO

1. The effect of two derivatives of salicylate, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) and 2-acetoxy-4-trifluoromethylbenzoic acid (triflusal), on the expression of several proteins displaying pro-inflammatory activities the regulation of which is associated to the transcription factor NF-kappaB, was assayed in the human astrocytoma cell line 1321N1. 2. Tumour necrosis factor-alpha (TNF-alpha) activated NF-kappaB as judged from both the appearance of kappaB-binding activity in the nuclear extracts, the degradation of IkappaB proteins in the cell lysates, and the activation of IkappaB kinases using an immunocomplex kinase assay with glutathione S-transferase (GST)-IkappaB proteins as substrates. 3. HTB up to 3 mM did not inhibit the nuclear translocation of NK-kappaB/Rel proteins as judged from electrophoretic mobility-shift assays; however, HTB inhibited the degradation of IkappaBbeta without significantly affecting the degradation of both IkappaBalpha and IkappaBepsilon. 4. In keeping with their inhibitory effect on IkappaBbeta degradation in the cell lysates, both HTB and triflusal inhibited the phosphorylation of GST-IkappaBbeta elicited by TNF-alpha, without affecting the phosphorylation of GST-IkappaBalpha. 5. The effect of both HTB and triflusal on kappaB-dependent trans-activation was studied by assaying the expression of both cyclo-oxygenase-2 (COX-2) and vascular cell adhesion molecule-1 (VCAM-1). HTB and triflusal inhibited in a dose-dependent manner the expression of COX-2 and VCAM-1 mRNA and the induction of COX-2 protein at therapeutically relevant concentrations. 6. These findings show the complexity of the biochemical mechanisms underlying the activation of NF-kappaB in the different cell types and extend the anti-inflammatory effects of HTB and triflusal to neural cells.


Assuntos
Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , NF-kappa B/metabolismo , Salicilatos/farmacologia , Western Blotting , Ciclo-Oxigenase 2 , DNA Complementar/biossíntese , Eletroforese , Humanos , Indicadores e Reagentes , Isoenzimas/biossíntese , Proteínas de Membrana , Proteínas de Neoplasias/biossíntese , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Prostaglandina-Endoperóxido Sintases/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Molécula 1 de Adesão de Célula Vascular/biossíntese
19.
J Med Chem ; 43(2): 214-23, 2000 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-10649977

RESUMO

A series of 3,4-diaryloxazolones were prepared and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). Extensive structure-activity relationship work was carried out within this series, and a number of potent and selective COX-2 inhibitors were identified. The replacement of the methyl sulfone group on the 4-phenyl ring by a sulfonamide moiety resulted in compounds with superior in vivo antiinflammatory properties. In the sulfonamide series, the introduction of a methyl group at the 5-position of the oxazolone ring gave rise to very COX-2-selective compounds but with decreased in vivo activity. Selected 3,4-diaryloxazolones exhibited excellent activities in experimental models of arthritis and hyperalgesia. The in vivo activity of these compounds was confirmed with the evaluation of their antipyretic effectiveness and their ability to inhibit migration of proinflammatory cells. As expected from their COX-2 selectivity, most of the active compounds lacked gastrointestinal toxicity in vivo in rats after a 4-day treatment of 100 mg/kg/day. Within this novel series, sulfonamides 9-11 have been selected for further preclinical evaluation.


Assuntos
Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/farmacologia , Oxazóis/síntese química , Oxazóis/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Experimental/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Febre/tratamento farmacológico , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Oxazóis/uso terapêutico , Prostaglandina-Endoperóxido Sintases/sangue , Ratos , Ratos Wistar , Relação Estrutura-Atividade
20.
Planta Med ; 65(7): 651-3, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10575379

RESUMO

The intestinal anti-inflammatory activity of two flavonoids, hesperidin and diosmin, was evaluated in the acute stage of the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. The results obtained showed that pretreatment with diosmin (10 mg/kg) or hesperidin (10 and 25 mg/kg) reduced colonic damage compared to TNBS control rats. This effect was confirmed biochemically by a reduction in colonic myeloperoxidase activity compared to non-treated colitic animals. Colonic glutathione levels in colitic animals were significantly increased after hesperidin or diosmin treatment. Diosmin decreased colonic MDA production and inhibited LTB4 synthesis, whereas hesperidin failed to do so. Conversely, only hesperidin improved colonic fluid absorption, which was impaired in colitic animals. In conclusion, both diosmin and hesperidin were able to prevent colonic inflammation, acting via a mechanism in which protection against oxidative insult may play a role.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Diosmina/farmacologia , Hesperidina/farmacologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Diosmina/uso terapêutico , Feminino , Hesperidina/uso terapêutico , Ratos , Ratos Wistar , Ácido Trinitrobenzenossulfônico
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