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1.
Gynecol Endocrinol ; 39(1): 2271072, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37857350

RESUMO

Background: In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users.Objective: To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety.Method: For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'.Results: Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman.Conclusion: Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.


Assuntos
Anticoncepcionais Orais Combinados , Progestinas , Feminino , Humanos , Anticoncepcionais Orais Combinados/efeitos adversos , Progestinas/uso terapêutico , América Latina , Etinilestradiol/efeitos adversos , Estrogênios/efeitos adversos , Saúde da Mulher
2.
Acta Biochim Biophys Sin (Shanghai) ; 55(4): 613-622, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36988350

RESUMO

Charcot-Leyden crystals (CLCs) are the hallmark of many eosinophilic-based diseases, such as asthma. Here, we report that reduced glutathione (GSH) disrupts CLCs and inhibits crystallization of human galectin-10 (Gal-10). GSH has no effect on CLCs from monkeys ( Macaca fascicularis or M. mulatta), even though monkey Gal-10s contain Cys29 and Cys32. Interestingly, human Gal-10 contains another cysteine residue (Cys57). Because GSH cannot disrupt CLCs formed by the human Gal-10 variant C57A or inhibit its crystallization, the effects of GSH on human Gal-10 or CLCs most likely occur by chemical modification of Cys57. We further report the crystal structures of Gal-10 from M. fascicularis and M. mulatta, along with their ability to bind to lactose and inhibit erythrocyte agglutination. Structural comparison with human Gal-10 shows that Cys57 and Gln75 within the ligand binding site are responsible for the loss of lactose binding. Pull-down experiments and mass spectrometry show that human Gal-10 interacts with tubulin α-1B, with GSH, GTP and Mg 2+ stabilizing this interaction and colchicine inhibiting it. Overall, this study enhances our understanding of Gal-10 function and CLC formation and suggests that GSH may be used as a pharmaceutical agent to ameliorate CLC-induced diseases.


Assuntos
Asma , Eosinófilos , Humanos , Eosinófilos/metabolismo , Galectinas/metabolismo , Glutationa , Lactose/farmacologia , Lactose/metabolismo
3.
Acta méd. peru ; 39(2): 120-127, abr.-jun. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1402999

RESUMO

ABSTRACT Objectives: To identify presumptive diagnoses of patients treated by synchronous teleorientation in the Ophthalmology Service of Cayetano Heredia Hospital (CHH) during the COVID-19 pandemic, describing their demographic characteristics and the percentage of patients referred for a face-to-face evaluation. Methods: A retrospective observational descriptive study with secondary analysis of a database collected from May to August 2020 consisting of patients treated with teleorientation in the Ophthalmology service at CHH. Results: Three hundred and eight patients were included in the analysis. The main presumptive diagnoses were dry eye syndrome (24,68%), glaucoma (18.51%), cataract (17,85%), post-operated (5,84%) and viral/bacterial conjunctivitis (5,52%). Most patients were female (64,29%) and they came from Metropolitan Lima (91,88%). The number of older adults was higher than that of non-older adults (51,29% vs 48,70%). Finally, the patients sent to the Ophthalmology service for a face-to-face appointment were 4,55%. Discussion: During the period of this study, the main presumptive diagnosis was dry eye syndrome. This result obtained is similar to other hospitals. The main presumptive diagnoses that required a face-to-face appointment were acute posterior vitreous detachment, glaucoma, age-related macular degeneration because they needed especial examination, like measuring the intraocular pressure and fundoscopy. Older adults required assistance more frequently compared to the non-older adult group (84.41% vs 59.57%, p< 0,001).


RESUMEN Objetivos: Identificar los diagnósticos presuntivos de pacientes tratados por teleorientación sincrónica en el servicio de oftalmología del Hospital Cayetano Heredia (HCH) durante la pandemia del COVID-19, describiendo sus características demográficas y el porcentaje de pacientes derivados para una evaluación presencial. Métodos: Estudio descriptivo observacional retrospectivo con análisis secundario de una base de datos recopilada de mayo a agosto de 2020 de pacientes tratados por teleorientación en el servicio de Oftalmología en el HCH. Resultados: Un total de 308 pacientes ingresaron para análisis. Los principales diagnósticos presuntivos fueron: síndrome de ojo seco (24,68 %), glaucoma (18,51 %), catarata (17,85 %), posoperado (5,84 %) y conjuntivitis viral/bacteriana (5,52 %). La mayoría fueron mujeres (64,29 %) y de Lima Metropolitana (91,88 %). El porcentaje de adultos mayores fue más alto que los no mayores (51,29 % vs 48,70 %). El porcentaje de pacientes citados en el servicio de oftalmología para cita presencial fue de 4,55 %. Discusión: Durante el período de este estudio, el principal diagnóstico presuntivo fue síndrome de ojo seco. Este resultado es similar al de otros hospitales. Los diagnósticos que requirieron una cita presencial fueron desprendimiento de vítreo posterior agudo, glaucoma y degeneración macular porque necesitaron de un examen especial como la determinación de la presión intraocular y el examen de fondo de ojo. Los adultos de más edad tuvieron mayor necesidad de asistencia familiar versus el grupo de no mayores (84,41 % vs 59,57 %, p< 0,001.

4.
Glycobiology ; 31(9): 1219-1229, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34080003

RESUMO

The gene for galectin-13 (Gal-13, placental protein 13) is only present in primates, and its low expression level in maternal serum may promote preeclampsia. In the present study, we used pull-down experiments and biolayer interferometry to assess the interaction between Gal-13 and actin. These studies uncovered that human Gal-13 (hGal-13) and Saimiri boliviensis boliviensis (sGal-13) strongly bind to α- and ß-/γ-actin, with Ca2+ and adenosine triphosphate, significantly enhancing the interactions. This in turn suggests that h/sGal-13 may inhibit myosin-induced contraction when vascular smooth muscle cells undergo polarization. Here, we solved the crystal structure of sGal-13 bound to lactose and found that it exists as a monomer in contrast to hGal-13 which is a dimer. The distribution of sGal-13 in HeLa cells is similar to that of hGal-13, indicating that monomeric Gal-13 is the primary form in cells. Even though sGal-13 binds to actin, hGal-13 ligand-binding site mutants do not influence hGal-13/actin binding, whereas the monomeric mutant C136S/C138S binds to actin more strongly than the wild-type hGal-13. Overall, our study demonstrates that monomeric Gal-13 binds to actin, an interaction that is independent of the galectin canonical ligand-binding site.


Assuntos
Actinas , Galectinas/metabolismo , Placenta , Proteínas da Gravidez/metabolismo , Actinas/metabolismo , Animais , Sítios de Ligação , Feminino , Células HeLa , Humanos , Ligantes , Placenta/metabolismo , Gravidez , Ligação Proteica
5.
Biochim Biophys Acta Gen Subj ; 1865(1): 129755, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011338

RESUMO

BACKGROUND: The structure of human galectin-16 (Gal-16) has yet to be solved, and its function has remained elusive. METHODS: X-ray crystallography was used to determine the atomic structures of Gal-16 and two of its mutants. The Gal-16 oligomer state was investigated by gel filtration, its hemagglutination activity was determined along with its ability to bind lactose using ITC. The cellular distribution of EGFP-tagged Gal-16 in various cell lines was also investigated, and the interaction between Gal-16 and c-Rel was assessed by pull-down studies, microscale thermophoresis and immunofluorescence. RESULTS: Unlike other galectins, Gal-16 lacks the ability to bind the ß-galactoside lactose. Lactose binding could be regained by replacing an arginine (Arg55) with asparagine, as shown in the crystal structures of two lactose-loaded Gal-16 mutants (R55N and R55N/H57R). Gal-16 was also shown to be monomeric by gel filtration, as well as in crystal structures. Thus, this galectin could not induce erythrocyte agglutination. EGFP-tagged Gal-16 was found to be localized mostly in the nucleus of various cell types, and can interact with c-Rel, a member of NF-κB family. CONCLUSIONS: Gal-16 exists as a monomer and its ligand binding is significantly different from that of other prototype galectins, suggesting that it has a novel function(s). The interaction between Gal-16 and c-Rel indicates that Gal-16 may regulate signal transduction pathways via the c-Rel hub in B or T cells at the maternal-fetal interface. GENERAL SIGNIFICANCE: The present study lays the foundation for further studies into the cellular and physiological functions of Gal-16.


Assuntos
Lactose/metabolismo , Linfócitos/metabolismo , Proteínas Proto-Oncogênicas c-rel/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Linhagem Celular , Cristalografia por Raios X , Humanos , Ligantes , Modelos Moleculares , Ligação Proteica , Conformação Proteica
6.
FEBS J ; 288(3): 1041-1055, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32525264

RESUMO

The expression of prototype galectin-14 (Gal-14) in human placenta is higher than any other galectin, suggesting that it may play a role in fetal development and regulation of immune tolerance during pregnancy. Here, we solved the crystal structure of dimeric Gal-14 and found that its global fold is significantly different from that of other galectins with two ß-strands (S5 and S6) extending from one monomer and contributing to the carbohydrate-binding domain of the other. The hemagglutination assay showed that this lectin could induce agglutination of chicken erythrocytes, even though lactose could not inhibit Gal-14-induced agglutination activity. Calorimetry indicates that lactose does not interact with this lectin. Compared to galectin-1, galectin-3, and galectin-8, Gal-14 has two key amino acids (a histidine and an arginine) in the normally conserved, canonical sugar-binding site, which are substituted by glutamine (Gln53) and histidine (His57), thus likely explaining why lactose binding to this lectin is very weak. Lactose was observed in the ligand-binding site of one Gal-14 structure, most likely because ligand binding is weak and crystals were allowed to grow over a long period of time in the presence of lactose. We also found that EGFP-tagged Gal-14 is primarily localized within the nucleus of different cell types. In addition, Gal-14 colocalized with c-Rel (a member of NF-κB family) in HeLa cells. These findings indicate that Gal-14 might regulate signal transduction pathways through NF-κB hubs. Overall, the present study provides impetus for further research into the function of Gal-14 in embryology.


Assuntos
Galectinas/química , Galectinas/genética , Regulação da Expressão Gênica no Desenvolvimento , Lactose/química , Domínios Proteicos , Linhagem Celular Tumoral , Cristalografia por Raios X , Feminino , Galectinas/metabolismo , Células HCT116 , Células HEK293 , Humanos , Células Jurkat , Lactose/metabolismo , Ligantes , Microscopia Confocal , Modelos Moleculares , Ligação Proteica
7.
Front Microbiol ; 11: 1050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528448

RESUMO

In green species, sucrose can help antagonize abiotic stress. Sucrose phosphate synthase (SPS) is a well-known rate-limiting enzyme in the synthesis of sucrose. To date, however, there is no known crystal structure of SPS from plant or cyanobacteria. In this study, we report the first co-crystal structure of SPS from Thermosynechococcus elongatus with UDP and sucrose-6-phosphate (S6P). Within the catalytic site, the side chains of His158 and Glu331, along with two phosphate groups from UDP, form hydrogen bonds with the four hydroxyl groups of the glucose moiety in S6P. This association causes these four hydroxyl groups to become partially negatively charged, thus promoting formation of the C1 oxocarbenium ion. Breakage of the hydrogen bond between His158 and one of the hydroxyl groups may trigger covalent bond formation between the C1 oxocarbenium ion and the C2 hydroxyl of fructose-6-phosphate. Consistent with our structural model, we observed that two SPS mutants, H158A and E331A, lost all catalytic activity. Moreover, electron density of residues from two loops (loop1 and loop2) in the SPS A-domain was not observed, suggest their dynamic nature. B-factor analysis and molecular dynamics stimulations of the full-length enzyme and A-domain indicate that both loops are crucial for binding and release of substrate and product. In addition, temperature gradient analysis shows that SPS exhibits its highest activity at 70°C, suggesting that this enzyme has the potential of being used in industrial production of S6P.

8.
Glycobiology ; 30(2): 120-129, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31584064

RESUMO

Galectin-13 (Gal-13) plays numerous roles in regulating the relationship between maternal and fetal tissues. Low expression levels or mutations of the lectin can result in pre-eclampsia. The previous crystal structure and gel filtration data show that Gal-13 dimerizes via formation of two disulfide bonds formed by Cys136 and Cys138. In the present study, we mutated them to serine (C136S, C138S and C136S/C138S), crystalized the variants and solved their crystal structures. All variants crystallized as monomers. In the C136S structure, Cys138 formed a disulfide bond with Cys19, indicating that Cys19 is important for regulation of reversible disulfide bond formation in this lectin. Hemagglutination assays demonstrated that all variants are inactive at inducing erythrocyte agglutination, even though gel filtration profiles indicate that C136S and C138S could still form dimers, suggesting that these dimers do not exhibit the same activity as wild-type (WT) Gal-13. In HeLa cells, the three variants were found to be distributed the same as with WT Gal-13. However, a Gal-13 variant (delT221) truncated at T221 could not be transported into the nucleus, possibly explaining why women having this variant get pre-eclampsia. Considering the normally high concentration of glutathione in cells, WT Gal-13 should exist mostly as a monomer in cytoplasm, consistent with the monomeric variant C136S/C138S, which has a similar ability to interact with HOXA1 as WT Gal-13.


Assuntos
Dissulfetos , Galectinas , Proteínas da Gravidez , Cristalografia por Raios X , Dissulfetos/química , Dissulfetos/metabolismo , Feminino , Galectinas/química , Galectinas/metabolismo , Células HeLa , Humanos , Oxirredução , Pré-Eclâmpsia/metabolismo , Gravidez , Proteínas da Gravidez/química , Proteínas da Gravidez/metabolismo , Domínios Proteicos , Relação Estrutura-Atividade
9.
Rehabil. integral (Impr.) ; 14(2): 81-90, dic. 2019. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1100524

RESUMO

INTRODUCCIÓN: El cuidado de un familiar dependiente implica un alto riesgo para el cuidador quien se ve propenso a padecer diversas alteraciones. Institutos Teletón a partir del año 2017 implementó el programa Cuidar Cuidándote, que trabaja con cuidadoras de personas dependientes, a través de un acompañamiento domiciliario en actividades de promoción del autocuidado, actividades de respiro y vinculación con la comunidad. OBJETIVO: Evaluar la efectividad del programa "Cuidar Cuidándote" del voluntariado Teletón, en la calidad de vida, sobrecarga y apoyo social de las cuidadoras de niños, niñas y jóvenes en situación de discapacidad con compromiso funcional severo, durante los años 2017 y 2018. METODOLOGÍA: Estudio experimental aleatorizado simple ciego de evaluación de intervención psicosocial en 25 cuidadoras de niños, niñas y adolescentes con discapacidad severa del Instituto Teletón Santiago. Se trabajó en dos grupos, el grupo experimental participó del programa Cuidar Cuidándote recibiendo 13 visitas domiciliarias, y el grupo control no participó del programa, quedando en lista de espera. Para la evaluación de la intervención se realizaron pruebas de calidad de vida, sobrecarga del cuidador y apoyo social percibido antes y después de la intervención. RESULTADOS: Se observó una disminución estadísticamente significativa (promedio de 11,6 puntos en escala de Zarit) en la sobrecarga en cuidadoras de grupo de intervención. No se encontraron diferencias estadísticamente significativas para apoyo social y calidad de vida. CONCLUSIÓN: El programa "Cuidar Cuidándote" logra disminuir el nivel de sobrecarga de las cuidadoras de niños, niñas y adolescentes con discapacidad severa.


INTRODUCTION: Caring for a dependent family member carries a high risk for the caregiver, who is prone to experiencing diverse disorders. In 2017, Teleton introduced the program "Cuidar Cuidándote", which offers in-home services for caregivers assisting dependent family members, providing support in activities to promote self-care, community involvement and respite care. OBJECTIVE: to do an assessment of the effectiveness of "Cuidar Cuidándote" program of Teleton's volunteer team, in terms of quality of life, work overload and social support for caregivers of children and young people with disabilities and severe functional impairment during 2017 and 2018. METHOD: A single-blind randomized experimental study to assess the psychosocial intervention in 25 caregivers of children and teenagers with severe disabilities, users of Instituto Teletón-Santiago. Caregivers were separated in two groups: an experimental group that participated in the "Cuidar Cuidándote" program including 13 home visits, and a control group that received no home visits. the effectiveness of the intervention was measured through different tests, such as quality of life, work overload, and social support as perceived before and after the intervention. RESULTS: A statistically significant reduction in caregiver work overload (average of 11.6 points on the Zarit Scale) was observed in the group of caregivers that received the home visits. No significant differences were observed in terms of social support and quality of life. CONCLUSION: This program achieves a reduction in the level of work overload for caregivers of children and teenagers with severe disabilities.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Avaliação de Programas e Projetos de Saúde , Cuidadores/psicologia , Pessoas com Deficiência , Qualidade de Vida/psicologia , Apoio Social
10.
Int J Mol Sci ; 20(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500178

RESUMO

All living things have pyrophosphatases that hydrolyze pyrophosphate and release energy. This energetically favorable reaction drives many energetically unfavorable reactions. An accepted catalytic model of pyrophosphatase shows that a water molecule activated by two divalent cations (M1 and M2) within the catalytic center can attack pyrophosphate in an SN2 mechanism and thus hydrolyze the molecule. However, our co-crystal structure of Acinetobacter baumannii pyrophosphatase with pyrophosphate shows that a water molecule from the solvent may, in fact, be the actual catalytic water. In the co-crystal structure of the wild-type pyrophosphatase with pyrophosphate, the electron density of the catalytic centers of each monomer are different from one another. This indicates that pyrophosphates in the catalytic center are dynamic. Our mass spectroscopy results have identified a highly conserved lysine residue (Lys30) in the catalytic center that is phosphorylated, indicating that the enzyme could form a phosphoryl enzyme intermediate during hydrolysis. Mutation of Lys30 to Arg abolished the activity of the enzyme. In the structure of the apo wild type enzyme, we observed that a Na+ ion is coordinated by residues within a loop proximal to the catalytic center. Therefore, we mutated three key residues within the loop (K143R, P147G, and K149R) and determined Na+ and K+-induced inhibition on their activities. Compared to the wild type enzyme, P147G is most sensitive to these cations, whereas K143R was inactive and K149R showed no change in activity. These data indicate that monovalent cations could play a role in down-regulating pyrophosphatase activity in vivo. Overall, our results reveal new aspects of pyrophosphatase catalysis and could assist in the design of specific inhibitors of Acinetobacter baumannii growth.


Assuntos
Acinetobacter baumannii/enzimologia , Modelos Moleculares , Conformação Proteica , Pirofosfatases/química , Sequência de Aminoácidos , Sítios de Ligação , Catálise , Domínio Catalítico , Difosfatos/química , Difosfatos/metabolismo , Ativação Enzimática , Hidrólise , Peptídeos , Fosforilação , Ligação Proteica , Pirofosfatases/metabolismo , Relação Estrutura-Atividade
11.
Front Cell Neurosci ; 8: 326, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25360084

RESUMO

The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca(2+) concentration and NMDA receptor (NMDAR) composition of GluN2 subunits. Pannexin 1 (Panx1), a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP), it remains unknown whether these channels also modulate long-term depression (LTD) or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory.

12.
Neuropharmacology ; 55(8): 1383-90, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18789952

RESUMO

The K+ channel blocker 4-aminopyridine (4-AP) stimulates the release of glutamate from nerve endings and induces seizures and neurodegeneration when perfused by microdialysis in rat hippocampus. In addition, there is a temporal correlation between the progress of neurodegeneration in the perfused hippocampus and the expression of the inducible cellular stress marker heat shock protein 70 (HSP70) in the non-damaged contralateral hippocampus. All these effects of 4-AP are prevented by the NMDA receptor antagonists 3-phosphonopropyl-piperazine-2-carboxilic acid (CPP) and (+)5-methyl-10,11-dyhydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801), indicating that they are due to NMDA receptor overactivation by excessive extracellular synaptic glutamate. We hypothesized that the induction of HSP70 in the non-damaged contralateral hippocampus should have a protective action against this excitotoxic effect. Here we demonstrate that 4-AP perfusion in one hippocampus prevented the neurotoxic effect of 4-AP when perfused by microdialysis in the contralateral hippocampus 24h later. However, both the stimulation of glutamate release and the EEG epileptiform discharges, which occur immediately after 4-AP perfusion, were similar after the first and the second perfusions. When CPP was coperfused with 4-AP during the first microdialysis, HSP70 induction in the contralateral hippocampus was prevented and the protection against the second 4-AP perfusion was abolished in 50% of the rats. These results suggest that HSP70 induction is an important cellular mechanism to protect vulnerable neurons from excitotoxic overactivation of glutamate receptors by endogenous glutamate, and may be relevant to pathological conditions in which extracellular endogenous glutamate is augmented, such as ischemia.


Assuntos
Ácido Glutâmico/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Hipocampo/metabolismo , Doenças Neurodegenerativas/patologia , 4-Aminopiridina , Animais , Contagem de Células , Modelos Animais de Doenças , Maleato de Dizocilpina/administração & dosagem , Eletroencefalografia , Lateralidade Funcional/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/administração & dosagem , Piperazinas/administração & dosagem , Ratos , Ratos Wistar , Fatores de Tempo
13.
Rev. centroam. obstet. ginecol ; 13(12): 53-57, abr.-jun. 2008. ilus
Artigo em Espanhol | LILACS | ID: lil-644041

RESUMO

Objetivo: demostrar que Drospirenona no disminuye los efectos del estradiol en la producción de óxido nítrico . Este estudio abierto incluyó a cuarenta y dos mujeres posmenopáusicas, no obesas de entre 40 a 55 años de edad, sin tratamiento hormonal, que cumpliera con los requisitos de la Sociedad Internacional de Menopausia para uso de Terapia Hormonal. A cada una de las pacientes se le efectuó determinaciones séricas de Lipoproteína de alta densidad (HDL), Lipoproteína de baja densidad (LDL)...


Assuntos
Feminino , Endotélio Vascular/fisiopatologia , Óxido Nítrico/uso terapêutico , Pós-Menopausa , Terapia de Reposição Hormonal/métodos
14.
Eur J Neurosci ; 22(12): 3067-76, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16367773

RESUMO

The intrahippocampal perfusion of 4-aminopyridine (4-AP) in the rat produces immediate seizures and delayed neuronal death, due to the overactivation of N-methyl-D-aspartate (NMDA) receptors by endogenous glutamate released from nerve endings. With the same time course, 4-AP also induces the expression of the cell stress marker heat shock protein 70 (HSP70) in the contralateral non-damaged hippocampus. We have used this experimental model to study the mechanisms of the delayed neuronal stress and death. The NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801), administered intraperitoneally 30 or 60 but not 120 min after 4-AP perfusion, when animals show intense electroencephalography epileptiform activity, prevented the delayed neurodegeneration whereas the seizures continued for about 3 h as in the control animals. With an identical time window, MK-801 treatment also modified the pattern of HSP70 expression; the protein was expressed in the protected perfused hippocampus but no longer in the undamaged contralateral hippocampus. The possible role of Ca2+ in the delayed cell death and HSP70 expression was also studied by coperfusing the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester) with 4-AP. This treatment resulted in protective and HSP70 effects very similar to those of MK-801. These results suggest that the seizures are not linked to neurodegeneration and that NMDA receptors need to be continuously overactivated by endogenous glutamate for at least 60 min in order to induce delayed neuronal stress and death, which are dependent on Ca2+ entry through the NMDA receptor channel.


Assuntos
Morte Celular/efeitos dos fármacos , Epilepsia/patologia , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Hipocampo/patologia , Neurônios/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Estresse Fisiológico/patologia , 4-Aminopiridina , Animais , Contagem de Células/métodos , Morte Celular/fisiologia , Quelantes/farmacologia , Modelos Animais de Doenças , Maleato de Dizocilpina/administração & dosagem , Interações Medicamentosas , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Eletroencefalografia/métodos , Epilepsia/induzido quimicamente , Epilepsia/complicações , Lateralidade Funcional , Ácido Glutâmico/metabolismo , Masculino , Microdiálise/métodos , Degeneração Neural/prevenção & controle , Neurônios/fisiologia , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/fisiologia , Estresse Fisiológico/etiologia , Fatores de Tempo
15.
Neuropharmacology ; 45(5): 649-60, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12941378

RESUMO

The intrahippocampal administration of 4-aminopyridine (4-AP) induces epileptic seizures and neurodegeneration, due probably to stimulation of glutamate release from synaptic terminals. We have studied the time course of the neurodegenerative changes produced by 4-AP, perfused through microdialysis cannulas in rat hippocampus, and correlated them with the expression of the inducible heat shock protein 70 (HSP70), detected immunocytochemically. Electroencephalographic seizure activity appeared immediately after the beginning of 4-AP perfusion. The first signs of histological neuronal damage were observed in CA1 and CA3 subfields of the perfused hippocampus 3 h after treatment and progressed until reaching a maximal neuronal loss at 24 h. In 4-AP-treated rats HSP70 was expressed mainly in neurons of the contralateral hippocampus, with a time course and cellular distribution very similar to the neurodegeneration observed in the perfused hippocampus, but no neuronal damage was observed. The N-methyl-D-aspartate (NMDA) receptor antagonists MK-801 and (3-phosphonopropyl)-piperazine-2-carboxylic acid prevented the seizures, the neurodegeneration and the expression of HSP70. These data demonstrate that the 4-AP-induced release of endogenous glutamate overactivates NMDA receptors in the perfused hippocampus and that the resulting neuronal hyperexcitability propagates to the contralateral hippocampus, generating a glutamate-mediated neuronal stress sufficient to induce the expression of HSP70 but not to produce neurodegeneration. These findings provide a useful model for investigating the relationships between neuronal hyperexcitation, neurodegeneration and the role of HSP expression.


Assuntos
4-Aminopiridina/farmacologia , Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Hipocampo/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Estresse Fisiológico/metabolismo , Animais , Anticonvulsivantes/farmacologia , Contagem de Células , Cromatografia Líquida de Alta Pressão , Maleato de Dizocilpina/farmacologia , Interações Medicamentosas , Eletroencefalografia , Epilepsia/fisiopatologia , Espaço Extracelular/metabolismo , Lateralidade Funcional , Hipocampo/anatomia & histologia , Hipocampo/metabolismo , Imuno-Histoquímica , Masculino , Microdiálise , Degeneração Neural , Fármacos Neuroprotetores/farmacologia , Piperazinas/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Córtex Somatossensorial/anatomia & histologia , Córtex Somatossensorial/efeitos dos fármacos , Córtex Somatossensorial/metabolismo , Estresse Fisiológico/induzido quimicamente , Fatores de Tempo
16.
Metro cienc ; 3(1): 33-6, abr. 1993. tab
Artigo em Espanhol | LILACS | ID: lil-135525

RESUMO

Efectos mecano-ventilatorios de la función respiratoria han sido atribuidos a los esteroides sexuales, sin embargo son limitados los reportes del estado fisiológico de parámetros espirométricos en el ciclo menstrual. En 50 mujeres jóvenes (20+ -1.5 años), eumenorreicas (6 meses), no fumadoras y con normopeso (IMC: 23.1+ -0.8); se evalúo de forma automatizada (Spiroanalizer ST90 Futuremed): capacidad vital forzada (CVF), volumen espiratorio máximo medio (MMEF), flujo espiratorio forzado al 50 por ciento de CVF (FEF50), máxima ventilación voluntaria (MVV) y el cociente FEV1/CVF. Distribuidas las mujeres en 4 grupos: Fase folicular precoz (FP:O-5d, n=21), fase folicular tardía (FT: 6-10d, n=12), fase ovulatoria (FO: 11-16d, n=6) y fase lútea (FL:18-28d, n=21); se observó: CVF(1) y FEV1 (1) similar en los 4 grupos, MMEF (1/s) Y MVV (1/min) inferiores en la FT (0,03) y FP(0.01), respectivamente el 80 en los 4 grupos, siendo máximo en FL (0,01). Además, en todos los grupos, los parámetros analizados superan el 90 por ciento de los valores predictivos (por edad, sexo, talla), excepto la MVV que osciló entre 58-78. Los resultados demuestran que, en mujeres jóvenes, eumenorreicas, no fumadoras existen variaciones en el estado fisiológico de los índices espirométricos en las diferentes fases del ciclo menstrual; lo cual debe ser tomado en cuenta en la práctica clínica.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Ciclo Menstrual , Espirometria/estatística & dados numéricos , Mulheres , Fase Folicular
17.
Metro cienc ; 2(2): 56-60, jul. 1992. tab
Artigo em Espanhol | LILACS | ID: lil-133244

RESUMO

Los parámetros funcionales obtenidos por espirometria son indicadores sensibles de la integridad funcional ventilatoria, y factores fisiológicos como el peso, talla, sexo, raza y altitud geográfica; son determinantes para su correcta interpretación. En éste estudio se analiza la capacidad vital forzada (CVF), el volumen generado al 1 seg de la espiración forzada (FE V1), el generado al 50//de la CVF (FEV 50), el flujo espiratorio máximo medio(MMEF), y el cociente FEV1/CVF; por medio de espirómetria automatizado. Se incluyen 34 hombres (H) y 31 mujeres (M) adultos jóvenes (20+-2 H vs 20+-2M,años), con nomopeso (IMC: 21 +- 2 H vs 22 +- 2 M); aparentemente sanos, no fumadores activos ni exfumadores y residentes a 2820 m/snm (Quito). Los valores teóricos y los observadores corregidos por edad, sexo, talla) fueron siempre estadisticamente superiores en H que en M. Los valores observados alcanzaron o superaron el 100 por ciento de los teóricos, sin diferencia entre sexos; excepto para el MMEF que fue superior H(142 +- 65 vs 115 +- 31 por ciento, p=0.04). El cociente FEV1/cvf demostró integridad ventilatoria en H y M: 93+-9 vs 94+-9por ciento(ns). Comparando con una población de sujetos similar a 150 m/snm (Austria), se observó que la CVF y el FEV1/CVF es superior en los sujetos analizados en Quito. Con los valores de refernecia internacional, tan sólo la CVF en M fue inferior. La población analizada, demuestra integridad funcional ventilatoria (FEV1/CVF 80//), corroborandose diferencias según el sexo y variaciones de adaptación crónica a la altitud (2820m/snm).Además, de forma preliminar se reportan valores de referencia local de parámetros espirométricos, en adultos jóvenes con normopeso y no fumadores.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adolescente/fisiologia , Adulto/fisiologia , Espirometria , Poluição por Fumaça de Tabaco , Espirometria , Espirometria/instrumentação
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