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1.
Cell Biosci ; 12(1): 10, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35090553

RESUMO

BACKGROUND: Obesity is caused by the enlargement of the white adipose tissue (WAT) depots, characterized by the hypertrophic enlargement of malfunctioning adipocytes within WAT which increases the storage of triglycerides (TG) in the lipid droplets (LD). Adipogenesis pathways as well as the expression and activity of some extracellular matrix receptors integrins are upregulated. Integrinß1 (INTB1) is the main isoform involved in WAT remodeling during obesity and insulin resistance-related diseases. We recently described Integrin Linked Kinase (ILK), a scaffold protein recruited by INTB1, as an important mediator of WAT remodeling and insulin resistance. As the few approved drugs to fight obesity have brought long-term cardiovascular side effects and given that the consideration of INTB1 and/or ILK modulation as anti-obesogenic strategies remains unexplored, we aimed to evaluate the anti-obesogenic capacity of the clinically approved anticoagulant Tirofiban (TF), stated in preclinical studies as a cardiovascular protector. METHODS: Fully differentiated adipocytes originating from C3H10T1/2 were exposed to TF and were co-treated with specific INTB1 blockers or with siRNA-based knockdown ILK expression. Lipid-specific dyes were used to determine the TG content in LD. The genetic expression pattern of ILK, pro-inflammatory cytokines (MCP1, IL6), adipogenesis (PPARγ, Leptin), thermogenesis (UCP1), proliferation (PCNA), lipid metabolism (FASN, HSL, ATGL), and metabolite transporters (FABP4, FAT, AQP7) were detected using quantitative PCR. Cytoskeletal actin polymerization was detected by confocal microscopy. Immunoblotting was performed to detect INTB1 phosphorylation at Thr788/9 and ILK activity as phosphorylation levels of protein kinase B (AKT) in Ser473 and glycogen synthase kinase 3ß (GSK3ß) at Ser9. TF was intraperitoneally administered once per day to wildtype and ILK knockdown mice (cKDILK) challenged with a high-fat diet (HFD) or control diet (STD) for 2 weeks. Body and WAT weight gains were compared. The expression of ILK and other markers was determined in the visceral epididymal (epi) and inguinal subcutaneous (sc) WAT. RESULTS: TF reduced TG content and the expression of adipogenesis markers and transporters in adipocytes, while UCP-1 expression was increased and the expression of lipases, cytokines or PCNA was not affected. Mechanistically, TF rapidly increased and faded the intracellular phosphorylation of INTB1 but not AKT or GSK3ß. F-actin levels were rapidly decreased, and INTB1 blockade avoided the TF effect. After 24 h, ILK expression and phosphorylation rates of AKT and GSK3ß were upregulated, while ILK silencing increased TG content. INTB1 blockade and ILK silencing avoided TF effects on the TG content and the transcriptional expression of PPARγ and UCP1. In HFD-challenged mice, the systemic administration of TF for several days reduced the weight gain on WAT depots. TF reduced adipogenesis and pro-inflammatory biomarkers and increased lipolysis markers HSL and FAT in epiWAT from HFD, while increased UCP1 in scWAT. In both WATs, TF upregulated ILK expression and activity, while no changes were observed in other tissues. In HFD-fed cKDILK, the blunted ILK in epiWAT worsened weight gain and avoided the anti-obesogenic effect of in vivo TF administration. CONCLUSIONS: ILK downregulation in WAT can be considered a biomarker of obesity establishment. Via an INTB1-ILK axis, TF restores malfunctioning hypertrophied WAT by changing the expression of adipocyte-related genes, increasing ILK expression and activity, and reducing TG storage. TF prevents obesity, a property to be added to its anticoagulant and cardiovascular protective advantages.

3.
Org Biomol Chem ; 14(40): 9549-9553, 2016 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-27722696

RESUMO

An ideal drug should be highly effective, non-toxic and be delivered by a convenient and painless single dose. We are still far from such optimal treatment but peptides, with their high target selectivity and low toxicity profiles, provide a very attractive platform from which to strive towards it. One of the major limitations of peptide drugs is their high clearance rates, which limit dosage regimen options. Conjugation to antibody Fc domains is a viable strategy to improve peptide stability by increasing their hydrodynamic radius and hijacking the Fc recycling pathway. We report the use of a split-intein based semi-synthetic approach to site-specifically conjugate a synthetic integrin binding peptide to an Fc domain. The strategy described here allows conjugating synthetic peptides to Fc domains, which is not possible via genetic methods, fully maintaining the ability of both the Fc domain and the bioactive peptide to interact with their binding partners.


Assuntos
Fragmentos Fc das Imunoglobulinas/metabolismo , Peptídeos Cíclicos/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Humanos , Hidrólise , Fragmentos Fc das Imunoglobulinas/química , Integrina alfaVbeta3/metabolismo
4.
Neuroscience ; 252: 289-301, 2013 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-23973620

RESUMO

Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 µg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain.


Assuntos
Encéfalo/metabolismo , Insulina/metabolismo , Leptina/metabolismo , Receptores de Somatostatina/biossíntese , Transdução de Sinais/fisiologia , Animais , Western Blotting , Encéfalo/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Imunoensaio , Injeções Intraventriculares , Leptina/administração & dosagem , Masculino , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Somatostatina/metabolismo , Regulação para Cima
5.
Free Radic Biol Med ; 61: 416-27, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23624332

RESUMO

Transforming growth factor type-ß1 (TGF-ß1) has been recognized as a central mediator in many pathological events related to extracellular matrix (ECM) proteins accumulation, where their locally increased expression has been implicated in the fibrosis process of numerous organs, including glomerular fibrosis in the kidney. We and others have reported the TGF-ß1 synthesis regulation by reactive oxygen species (ROS), and moreover we also described the implication of integrin-linked kinase (ILK) in the AP-1-dependent TGF-ß1 up-regulation. Thus, we propose here that hydrogen peroxide (H2O2)-dependent TGF-ß1 regulation may be mediated by ILK activation. First we confirmed the increase in TGF-ß1 expression in human mesangial cells (HMC) after treatment with H2O2 or with an alternative H2O2-generating system such as the glucose-oxidase enzyme (GOX). By using immunoblotting, immunofluorescence, and ELISA techniques, we demonstrate that extracellular H2O2 up-regulates TGF-ß1 transcription, as well as increases TGF-ß1 promoter activity. Furthermore, catalase-decreased intracellular H2O2 abolished TGF-ß1 up-regulation. The use of pharmacological inhibitors as well as knockdown of ILK with small interfering RNA (siRNA) demonstrated the implication of a PI3K/ILK/AKT/ERK MAPK signaling pathway axis in the H2O2-induced TGF-ß1 overexpression. Finally, we explored the physiological relevance of these findings by treating HMC with angiotensin II, a known stimuli of H2O2 synthesis. Our results confirm the relevance of previous findings after a more physiological stimulus. In summary, our results provide evidence that ILK activity changes may act as a mechanism in response to different stimuli such as H2O2 in the induced TGF-ß1 up-regulation in pathological or even physiological conditions.


Assuntos
Peróxido de Hidrogênio/metabolismo , Proteínas Serina-Treonina Quinases/fisiologia , Fator de Crescimento Transformador beta1/biossíntese , Angiotensina II/farmacologia , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Glucose Oxidase/fisiologia , Humanos , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Regulação para Cima
6.
Am J Physiol Lung Cell Mol Physiol ; 301(6): L872-80, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21908592

RESUMO

Pulmonary hypertension occurs with prolonged exposure to chronic hypoxia in both adults and neonates. The Ca(2+)-dependent transcription factor, nuclear factor of activated T cells isoform c3 (NFATc3), has been implicated in chronic hypoxia-induced pulmonary arterial remodeling in adult mice. Therefore, we hypothesized that NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice. The aim of this study was to determine whether 1) NFATc3 mediates chronic hypoxia-induced increases in right ventricular systolic pressure in adult mice; 2) NFATc3 is activated in neonatal mice exposed to chronic hypoxia; and 3) NFATc3 is involved in chronic hypoxia-induced right ventricular hypertrophy and pulmonary vascular remodeling in neonatal mice. Adult mice were exposed to hypobaric hypoxia for 2, 7, and 21 days. Neonatal mouse pups were exposed for 7 days to hypobaric chronic hypoxia within 2 days after delivery. Hypoxia-induced increases in right ventricular systolic pressure were absent in NFATc3 knockout adult mice. In neonatal mice, chronic hypoxia caused NFAT activation in whole lung and nuclear accumulation of NFATc3 in both pulmonary vascular smooth muscle and endothelial cells. In addition, heterozygous NFATc3 neonates showed less right ventricular hypertrophy and pulmonary artery wall thickness in response to chronic hypoxia than did wild-type neonates. Our results suggest that NFATc3 mediates pulmonary hypertension and vascular remodeling in both adult and neonatal mice.


Assuntos
Hipertensão Pulmonar/metabolismo , Fatores de Transcrição NFATC/metabolismo , Artéria Pulmonar/patologia , Análise de Variância , Animais , Animais Recém-Nascidos , Apoptose , Núcleo Celular/metabolismo , Proliferação de Células , Técnicas de Inativação de Genes , Genes Reporter , Heterozigoto , Hipertensão Pulmonar/complicações , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/metabolismo , Hipóxia , Luciferases/biossíntese , Luciferases/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Fatores de Transcrição NFATC/genética , Transporte Proteico , Artéria Pulmonar/metabolismo
9.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. impr.) ; 34(8): 411-414, oct. 2008. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-73652

RESUMO

Presentamos el caso de una mujer adolescente que comienza con un cuadro de poliartralgias, exantema, rash y fiebre. Se confirma el diagnóstico de sospecha inicial de lupus eritematoso sistémico (LES) tanto por la clínica como por las múltiples alteraciones analíticas y la presencia de derrame pericárdico. El LES es una enfermedad relativamente frecuente, con claro predominio de sexo femenino, de etiología multifactorial y que cursa en brotes con períodos de inactividad. Dada la afectación multisistémica, la clínica es variada, con predominio de manifestaciones musculoesqueléticas y mucocutáneas. El pronóstico de esta enfermedad ha mejorado radicalmente en los últimos años gracias a los avances en su diagnóstico y tratamiento. Los médicos de Atención Primaria tenemos un papel fundamental en dicho diagnóstico y su posterior seguimiento. El futuro es alentador, con múltiples moléculas en estudio actualmente (AU)


We present the case of an adolescent woman who began with a picture of polyarthralgias, exanthema, rash and fever. The initial suspected diagnosis of systemic lupus erythematosus (SLE) has been confirmed by both the symptoms and by the multiple analytical alterations and the presence of pericardial effusion. SLE is a relatively common disease with clear predominance in the female gender, that has a multifactorial etiology and that occurs with outbreaks with periods of inactivity. Given the multisystemic involvement, the symptoms are varied with predominance of musculoskeletal and mucocutaneous manifestations. The prognosis of this disease has radically improved in recent years thanks to the advances in its diagnosis and treatment. Primary care doctors play an essential role in such diagnoses and its later follow-up. The future with the multiple molecules currently being studied is encouraging (AU)


Assuntos
Humanos , Feminino , Adolescente , Lúpus Eritematoso Sistêmico/diagnóstico , Artralgia/etiologia , Febre/etiologia , Exantema/etiologia , Artralgia/diagnóstico , Exantema/diagnóstico , Prognóstico , Diagnóstico Clínico
10.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. impr.) ; 34(10): 524-526, dic. 2008. ilus
Artigo em Espanhol | IBECS | ID: ibc-74113

RESUMO

La tuberculosis miliar es una rara presentación de tu- berculosis extrapulmonar en pacientes inmunocompetentes. Aunque puede presentarse a cualquier edad, tiene una mayor incidencia en pacientes de edad avanzada e inmunodeprimidos. Presenta una clínica inespecífica, donde la fiebre de larga evolución es el dato más característico. Para el diagnóstico es muy útil el patrón radiológico miliar, aunque debe intentarse una confirmación microbiológica en muestras respiratorias, sangre o líquido cefalorraquídeo. Un rápido diagnóstico e inicio de tratamiento reducen el riesgo de mortalidad de esta enfermedad con todavía alta letalidad. Presentamos el raro caso de una tuberculosis miliar en una paciente joven e inmunocompetente como causa de fiebre de larga evolución (AU)


Miliary tuberculosis is a rare presentation of extrapulmonarytuberculosis in immunocompetent patients. Although itcan appear at any age, it has a greater incidence in elderlyand immunodepressed patients. It presents an unspecific clinicalpattern, with long-term fever being the main characteristic.The radiological miliary pattern is very useful for diagnosis,although microbiological confirmation in respiratory,blood or cerebrospinal fluid samples should be attempted.An early diagnosis and beginning of treatment reduce therisk of mortality of this disease, which presents high lethality.We present the rare case of miliary tuberculosis in ayoung and immunocompetent female patient as a consequenceof long-term fever (AU)


Assuntos
Humanos , Feminino , Adulto , Tuberculose Miliar/diagnóstico , Imunocompetência , Tuberculose Miliar/tratamento farmacológico , Tuberculose Miliar/etiologia , Isoniazida/uso terapêutico , Pirazinamida/uso terapêutico
12.
Rev. biol. trop ; 56(3): 1135-1147, sep. 2008. graf, tab
Artigo em Inglês | LILACS | ID: lil-637853

RESUMO

The aim of the present study was to compare the abundance and species richness of zoo-heleoplankton bigger than 53 µm in an annual cycle under similar climate conditions in three artificial ponds, in order to observe the changes during an annual cycle. Samples were taken monthly from June 1993 to July 1994 in Corrientes, Argentina. The first pond (A) was covered an 80% by Eichhornia crassipes (Mart.), the second one (B) with bloom of Microcystis aeruginosa (Kurtzing) and the last one (C) with organic matter deposited in the bottom. The water was more acidic at pond A, and the water at pond B contained more dissolved oxygen concentration than the water at the other two ponds. The zoo-heleoplankton densities varied between 20-1728 ind.l-1 at pond A, 42-4082 ind.l-1 at pond B and 148-2447 ind.l-1 at pond C. The maximum zoo-heleoplankton abundance was found in the pond with cyanobacteria bloom during Autumn 1994 and the minimum abundance was found in the one with a predominance of E. crassipes. The rank of species richness was pond A > pond B > pond C. Rotifera was the most abundant group in pond A whereas the larval stages of Copepoda were abundant in the other two ponds. Anuraeopsis navicula Rousselt 1910 was the dominant population in the pond with macrophytes prevalence. Brachionus calyciflorus Pallas 1776 and larval stage of Copepoda had variable proportions in the pond with cyanobacteria bloom. Thermocyclops decipiens (Kiefer 1929) was present during the annual cycle only in the pond with organic matter deposited in the bottom. The succession of taxa was observed in the pond with coverage of aquatic macrophytes and with cyanobacteria bloom. Differences in species richness and low similarity in zoo-heleoplankton between ponds were determined by differences in the quality of the water in relation to the presence of macrophytes, cyanobacteria, organic matter deposited in the bottom and fish predation. Multiple regression analysis (stepwise) revealed that water transparency, dissolved oxygen and conductivity were the environmental variables that explained more than 42% of variability in the abundance of the dominant species. Rev. Biol. Trop. 56 (3): 1135-1147. Epub 2008 September 30.


La finalidad del presente estudio fue comparar la abundancia y riqueza de especies del zoo-heleoplancton mayor de 53 µm, en un ciclo anual bajo condiciones climáticas similares en tres estanques artificiales, con el propósito de observar los cambios durante un ciclo anual. Las muestras fueron tomadas mensualmente desde junio de 1993 hasta julio de 1994 en Corrientes, Argentina. El primer estanque (A) estuvo cubierto un 80% por E. crassipes, el segundo estanque (B) con floraciones de M. aeruginosa y el tercer estanque (C) con materia orgánica depositada en el fondo. El agua fue más ácida en el estanque A y tuvo más concentración de oxígeno disuelto en el B. La densidad del zoo-heleoplancton fue variable entre 20-1728 ind.l-1 en el estanque A, 42-4082 ind.l-1 en el estanque B y 148-2447 ind.l-1 en el estanque C. El rango de la riqueza de especies fue estanque A> estanque B> estanque C. La máxima abundancia del zoo-heleoplancton se encontró en el estanque con floraciones de cianobacterias y la mínima entre macrófitas de E. crassipes. Rotifera fue el grupo más abundante en el estanque con presencia de macrófitas. Los estadios larvales de Copepoda fueron abundantes en los estanques con materia orgánica depositada en el fondo y con dominancia de cianobacterias. A. navicula fue la población dominante en el agua libre del estanque con predominio de macrófitas. B. calyciflorus y estadios larvales de Copepoda tuvieron proporciones variables en el estanque con cianobacterias. T. decipiens fue la única población presente en el estanque con materia orgánica depositada en el fondo. Se observó un patrón de sucesión de los taxa en el estanque con importante cobertura de macrófitas acuáticas y con floraciones de cianobacterias. Las diferencias en la riqueza de especies y la baja similitud del zoo-heleoplancton entre los estanques estuvieron determinadas por la calidad del agua en relación con la presencia de macrófitas, cianobacterias, materia orgánica depositada en el fondo y peces. El análisis de regresión múltiple (stepwise) reveló que la transparencia del agua, el oxígeno disuelto y la conductividad fueron las variables ambientales que explican más de 42% de variabilidad en la abundancia de las especies dominantes.


Assuntos
Animais , Cladocera/classificação , Copépodes/classificação , Ecossistema , Peixes/classificação , Plantas/classificação , Rotíferos/classificação , Argentina , Água Doce/química , Água Doce/microbiologia , Densidade Demográfica , Estações do Ano , Zooplâncton/classificação
13.
Puesta día urgenc. emerg. catastr ; 8(2): 101-104, abr.-jun. 2008. ilus
Artigo em Espanhol | IBECS | ID: ibc-77924

RESUMO

El traumatismo craneoencefálico (TCE) constituye unimportante problema de salud en el mundo occidental, constituyendola primera causa demortalidad en el paciente politraumatizadoy la principal causa de discapacidad de largaduración tras traumatismo. Aunque el TCE penetrante esreconocido y tratado inmediatamente, su versión cerradasigue corriendo el riesgo de no ser detectada. La principalresponsabilidad del primer interviniente en el ámbito prehospitalarioes detectar la necesidad de pruebas y tratamientourgentes, trasladando al lesionado de forma adecuada alcentro adecuado. Adaptando el algoritmo diseñado por elDefense and Veterans Brain Injury CenterWorking Group onthe Acute Management of Mild Traumatic Brain Injury inMilitary Operational Settings a nuestro medio civil extrahospitalariocreemos que el primer interviniente tiene una herramientaadecuada, simple, segura y eficaz, para realizar conéxito esa primera evaluación (AU)


Traumatic brain injury (TBI) represents an importanthealth problem in the western world, being considered thefirst cause of death in the trauma patient and the maincause of long term disability following trauma. Althoughthe penetrating trauma is quickly recognized and treated,its closed version is still at risk of being missed, particularlyin mild cases. The main responsibility of the first responderin the pre-hospital setting is to detect the need of urgenttests and treatment, transferring the patient “to the rightplace, by the right means of transport and in the right way”.We believe that to adapt the algorithm designed by theDefense and Veterans Brain Injury Center Working Groupon the Acute Management of Mild Traumatic Brain injuryin Military Operational Settings to our pre-hospital environmentwill provide the first responder with a suitable,simple, safe and efficient tool to deal successfully with thatvery first evaluation (AU)


Assuntos
Humanos , Serviços Médicos de Emergência/métodos , Traumatismos Craniocerebrais/terapia , Protocolos Clínicos , Medicina Militar , Algoritmos
14.
Rev Biol Trop ; 56(3): 1135-47, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19419034

RESUMO

The aim of the present study was to compare the abundance and species richness of zoo-heleoplankton bigger than 53 microm in an annual cycle under similar climate conditions in three artificial ponds, in order to observe the changes during an annual cycle. Samples were taken monthly from June 1993 to July 1994 in Corrientes, Argentina. The first pond (A) was covered an 80% by Eichhornia crassipes (Mart.), the second one (B) with bloom of Microcystis aeruginosa (Kurtzing) and the last one (C) with organic matter deposited in the bottom. The water was more acidic at pond A, and the water at pond B contained more dissolved oxygen concentration than the water at the other two ponds. The zoo-heleoplankton densities varied between 20-1728 ind.l(-1) at pond A, 42-4082 ind.l(-1) at pond B and 148-2447 ind.l(-1) at pond C. The maximum zoo-heleoplankton abundance was found in the pond with cyanobacteria bloom during Autumn 1994 and the minimum abundance was found in the one with a predominance of E. crassipes. The rank of species richness was pond A > pond B > pond C. Rotifera was the most abundant group in pond A whereas the larval stages of Copepoda were abundant in the other two ponds. Anuraeopsis navicula Rousselt 1910 was the dominant population in the pond with macrophytes prevalence. Brachionus calyciflorus Pallas 1776 and larval stage of Copepoda had variable proportions in the pond with cyanobacteria bloom. Thermocyclops decipiens (Kiefer 1929) was present during the annual cycle only in the pond with organic matter deposited in the bottom. The succession of taxa was observed in the pond with coverage of aquatic macrophytes and with cyanobacteria bloom. Differences in species richness and low similarity in zoo-heleoplankton between ponds were determined by differences in the quality of the water in relation to the presence of macrophytes, cyanobacteria, organic matter deposited in the bottom and fish predation. Multiple regression analysis (stepwise) revealed that water transparency, dissolved oxygen and conductivity were the environmental variables that explained more than 42% of variability in the abundance of the dominant species.


Assuntos
Cladocera/classificação , Copépodes/classificação , Ecossistema , Peixes/classificação , Plantas/classificação , Rotíferos/classificação , Animais , Argentina , Água Doce/química , Água Doce/microbiologia , Densidade Demográfica , Estações do Ano , Zooplâncton/classificação
15.
Phytomedicine ; 13(1-2): 16-22, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16360928

RESUMO

Clinical evidence indicates that traditional Chinese medicine (TCM) drugs can reduce stroke-inflicted brain damage. To date, the molecular basis of the apparent neuroprotective effects of these TCM drugs remains largely obscure. Several lines of evidence indicate that the activation of cell death programs leads to the loss of neurons during the reperfusion phase of ischemic stroke. In particular, activation of caspases (cysteinyl aspartate-specific proteinases) is a critical step in neuronal apoptosis. Using nuclear magnetic resonance (NMR) and fluorescence assays, we screened a collection of 58 TCM drugs that are commonly used in stroke therapy for caspase inhibitory activity. We found that aqueous extracts of Lianqiao (Fructus Forsythiae) and Shouwuteng (Caulis Polygoni multiflori) blocked the activity of the initiator caspase-8 as well as the effector caspase-3 and caspase-7 in a dose-dependent manner with an IC(50)10 microg/ml. Identification of caspase inhibitory activity of these TCM drugs, allows the formulation of testable hypotheses and design of further investigations aimed at the elucidation of the molecular basis of TCM stroke therapy.


Assuntos
Inibidores de Caspase , Medicamentos de Ervas Chinesas/farmacologia , Caspase 3 , Caspase 7 , Caspase 8 , Caspases/metabolismo , Medicamentos de Ervas Chinesas/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia
16.
Am J Physiol Cell Physiol ; 285(4): C891-8, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12814915

RESUMO

cGMP is generated in endothelial cells after stimulation of soluble guanylyl cyclase (sGC) by nitric oxide (NO) or of particulate guanylyl cyclase (pGC) by natriuretic peptides (NP). We examined whether localized increases in cytosolic cGMP have distinct regulatory roles on the contraction induced by H2O2 treatment in human umbilical vein endothelial cells. cGMP concentrations and temporal dynamics were different upon NO stimulation of sGC or C-type NP (CNP) activation of pGC and did not correlate with their relaxing effects measured as planar cell surface area after H2O2 challenge. cGMP production due to sGC stimulation was always smaller and more brief than that induced by pGC stimulation with CNP, which was greater and remained elevated longer. The NO effects on cell relaxation were cGMP dependent because they were blocked by sGC inhibition with 1H-(1,2,4)Oxadiazolo(4,3-a)quinoxaline-1-one and mimicked by 8-Br-cGMP. An antagonist of the cGMP-dependent protein kinase type-I (PKG-I) also inhibited the NO-induced effects. The cell contraction induced by H2O2 produces myosin light chain (MLC) phosphorylation and NO prevented it completely, whereas CNP only produced a partial inhibition. Transfection with a dominant negative form of PKG type-I alpha completely reversed the NO-induced effects on MLC phosphorylation, whereas it only partially inhibited the effects due to CNP. Taken together, these results demonstrate that the NO/sGC/cGMP pathway induces endothelial cell relaxation in a more efficient manner than does CNP/pGC/cGMP pathway, an effect that might be related to a selective stimulation of PKG-1 alpha by NO-derived cGMP. Consequently, stimulated PKG-I alpha may phosphorylate important protein targets that are necessary to inhibit the endothelial contractile machinery activated by oxidative stress.


Assuntos
Endotélio Vascular/fisiologia , Guanilato Ciclase/metabolismo , Vasodilatação/fisiologia , Células Cultivadas , GMP Cíclico/farmacologia , GMP Cíclico/fisiologia , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Combinação de Medicamentos , Endotélio Vascular/citologia , Ativação Enzimática/fisiologia , Humanos , Peróxido de Hidrogênio/farmacologia , Isoenzimas/metabolismo , Peptídeo Natriurético Tipo C/metabolismo , Peptídeo Natriurético Tipo C/farmacologia , Óxido Nítrico/farmacologia , Óxido Nítrico/fisiologia , Oxidantes/farmacologia , Solubilidade , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
19.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 27(3): 103-106, mar. 2000. ilus
Artigo em Es | IBECS | ID: ibc-20925

RESUMO

El cáncer de mama es el tumor maligno más frecuente y la primera causa de muerte por cáncer en las mujeres. La mayoría de las neoplasias malignas son adenocarcinomas, y desde el punto de vista arquitectural la forma más frecuente es el carcinoma ductal infiltrante, seguida del lobulillar infiltrante. Ambos tipos histológicos pueden diseminarse por vía hematógena a cualquier órgano, siendo el hueso, pulmón e hígado los más afectados con más frecuencia. Otras estructuras como el peritoneo, meninges o aparato genital se afectan más raramente, y en estos casos el tipo lobulillar infiltrante es el causante de las metástasis la mayor parte de las veces. Presentamos el caso clínico de una paciente de 44 años sometida en nuestro servicio a tratamiento quirúrgico mediante mastectomía radical modificada por tumoración mamaria, cuyo resultado anatomopatológico fue carcinoma ductal con áreas de lobulillar infiltrante. En el curso del seguimiento clínico, y a los 47 meses de la intervención, se objetiva un incremento de los marcadores tumorales, así como una masa bilateral ovárica cuyo origen metastásico es comprobado tras la exéresis quirúrgica. Este caso nos sirve para hacer hincapié en la condición de enfermedad sistémica que caracteriza al cáncer de mama, y en la posibilidad de metástasis en órganos diferentes de los habituales, incluido el aparato genital, en especial si el tumor primario tiene componente lobulillar (AU)


Assuntos
Feminino , Pessoa de Meia-Idade , Humanos , Biópsia/métodos , Mamografia/métodos , Carcinoma/complicações , Carcinoma/diagnóstico , Tomografia Computadorizada de Emissão/métodos , Paclitaxel/uso terapêutico , Metástase Neoplásica/fisiopatologia , Metástase Neoplásica/diagnóstico , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Doxorrubicina/uso terapêutico , Pelve/patologia , Pelve , Biomarcadores Tumorais/análise , Biomarcadores Tumorais
20.
Medifam (Madr.) ; 10(2): 114-118, mar. 2000. ilus
Artigo em Es | IBECS | ID: ibc-264

RESUMO

La tuberculosis continúa siendo la enfermedad infecciosa más importante a nivel mundial, aunque la osteomielitis tuberculosa cada vez se ve con menos frecuencia en los países desarrollados. El diagnóstico de la tuberculosis osteoarticular puede demorarse durante varios meses debido a una baja sospecha clínica. Clínicamente es diferente según la localización, pudiendo presentarse como un absceso frío. Las lesiones radiológicas no son específicas y el diagnóstico de certeza se realiza mediante cultivo en medio específico. El tratamiento sigue siendo un tema en discusión. Presentamos un caso de osteomielitis tuberculosa que debutó como una tumoración abscesificada en tercio superior del brazo derecho de varios meses de evolución, cuyo diagnóstico y tratamiento fue realizado en Atención Primaria. Los médicos debemos pensar siempre en la tuberculosis, ya que es una enfermedad prevalente, transmisible, prevenible y curable (AU)


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Assuntos
Masculino , Pessoa de Meia-Idade , Humanos , Osteomielite/diagnóstico , Osteomielite/terapia , Tuberculose Osteoarticular , Abscesso/diagnóstico , Abscesso/terapia , Atenção Primária à Saúde
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