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1.
J Endocrinol Invest ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38337094

RESUMO

PURPOSE: Liver-expressed antimicrobial peptide 2 (LEAP-2) has been recently identified as the endogenous non-competitive allosteric antagonist of the growth hormone secretagogue receptor 1a (GHSR1a). In rodents, LEAP-2 blunts ghrelin-induced feeding and its plasma levels are modulated in response to nutritional status, being decreased upon fasting and increased in high-fat diet (HFD) fed mice. Clinical data support the regulation of circulating LEAP-2 by nutrient availability in humans. In this work, our primary objective was to examine the chronic effects of ghrelin and LEAP-2 administration on food intake, adiposity, and energy expenditure in young mice subjected to standard and HFD at both room temperature and at thermoneutrality. Furthermore, we aimed to assess the impact of these two hormones on aging mice. RESULTS: Our results indicate that LEAP-2 produces a significant decrease of body weight and adiposity, an increase in energy expenditure, and activation of the thermogenic program in white and brown adipose tissue depots. However, this effect is not maintained under HFD or under thermoneutral conditions and is only partially observed in aging mice. CONCLUSION: In summary our studies describe the central effects of LEAP-2 within distinct experimental contexts, and contribute to the comprehension of LEAP-2's role in energy metabolism.

2.
O.F.I.L ; 31(3): 281-284, July-September 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-224572

RESUMO

Objetivo: Evaluar la efectividad de icatibant en el tratamiento del angioedema inducido por IECA (AII), en un centro sin protocolización previa del manejo.Método: Estudio observacional retrospectivo y descriptivo. Se incluyeron pacientes diagnosticados de AII y tratados con icatibant 30 mg entre mayo 2015-diciembre 2017. Las variables de resultado principal y secundaria fueron: tiempo hasta resolución completa y tiempo hasta primera mejoría; respectivamente.Resultados: Cinco pacientes, mediana de edad 76 años (46-81); cuatro mujeres y un varón. Todos caucásicos. Medianas de tiempo hasta resolución completa y hasta primera mejoría: 23 horas (IQR 20,0-25,0) y 3 horas (IQR 3,0-6,0); respectivamente.Conclusiones. El inicio temprano del tratamiento anti-bradicinérgico puede resultar clave para la evolución del cuadro. Para alcanzar la máxima efectividad, se reduzcan las morbilidades asociadas, los ingresos en UCI y el tiempo de estancia hospitalaria, resulta primordial la elaboración de protocolos locales que tengan en cuenta las particularidades de cada centro. (AU)


Objetive: To assess the effectiveness of icatibant in the management of angiotensin-converting enzyme inhibitor-induced angioedema (AII) in a hospital without a treatment guidance.Methods: Observational, retrospective and descriptive study. All patients diagnossed with AII and treated with icatibant 30 mg between May 2015-December 2017 were included. The primary and secondary end-points were: time to total resolution and time to first improvement; respectively.Results: Five patients, median age 76 years (46-81). Four women and a man. All of them Caucasian. Median time to total resolution and to first improvement: 23 hours (IQR 20.0-25.0) and 3 hours (IQR 3.0-6.0); respectively.Conclusion: The early start with the anti-bradicinergic therapy may be key to the AII evolution. To achieve the maximum effectiveness and to get reduced the associated morbidity, the ICU admission and the time to discharge, the development of local protocols considering the particularities of each center is highly necessary. (AU)


Assuntos
Humanos , Masculino , Feminino , Idoso , Angioedema/terapia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos Retrospectivos , Epidemiologia Descritiva , Resultado do Tratamento
3.
Phys Rev Lett ; 126(22): 220402, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34152193

RESUMO

Conventional control strategies for nitrogen-vacancy centers in quantum sensing are based on a two-level model of their triplet ground state. However, this approach fails in regimes of weak bias magnetic fields or strong microwave pulses, as we demonstrate. To overcome this limitation, we propose a novel control sequence that exploits all three levels by addressing a hidden Raman configuration with microwave pulses tuned to the zero-field transition. We report excellent performance in typical dynamical decoupling sequences, opening up the possibility for nano-NMR operation in low field environments.

4.
Clin. transl. oncol. (Print) ; 20(10): 1345-1352, oct. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-173723

RESUMO

Purpose: To analyse any delays in breast cancer diagnosis and surgical treatment, influence of clinical and biological factors and influence of delays on survival. Methods/patients: A descriptive, observational, and retrospective study was conducted between 2006 and 2016 on stages I-III breast cancer patients. This is a retrospective review of health records to collect data on delays, patients’ clinical data, biological features of the tumour and information on treatment. Mortality data from the National Death Index. Results: In 493 evaluable patients, the median of days from the first symptom to mammography, biopsy, and surgery was 41, 57, and 92, respectively. The median of days from screening mammography to biopsy and surgery was 10 and 51, respectively. From biopsy to surgery, the median was 34 days in every case. Over the last 5 years, an increase in biopsy-surgery delay has been observed (p = 0.0001). Tumour stages I and II vs. stage III (RR 1.74. 95% CI 1.08-2.80, p = 0.027), diagnosis in screening (RR 0.66. 95% CI 0.45-0.96, p = 0.030), and use of magnetic resonance imaging (RR 2.08. 95 CI 1.21-3.56, p = 0.008) condition a greater biopsy-surgery delay. No influence of delays on survival has been identified. Conclusions: Delays in diagnosis and surgery in the case of women diagnosed on the basis of symptoms may be improved. There is a temporary tendency to a greater delay in surgery. Some clinical and biological factors must be taken into account to optimise delays. Survival results are not adversely affected by delays


No disponible


Assuntos
Humanos , Feminino , Neoplasias da Mama/epidemiologia , Tempo para o Tratamento/estatística & dados numéricos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Detecção Precoce de Câncer , Diagnóstico Tardio/estatística & dados numéricos , Taxa de Sobrevida
5.
Clin Transl Oncol ; 20(10): 1345-1352, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29633184

RESUMO

PURPOSE: To analyse any delays in breast cancer diagnosis and surgical treatment, influence of clinical and biological factors and influence of delays on survival. METHODS/PATIENTS: A descriptive, observational, and retrospective study was conducted between 2006 and 2016 on stages I-III breast cancer patients. This is a retrospective review of health records to collect data on delays, patients' clinical data, biological features of the tumour and information on treatment. Mortality data from the National Death Index. RESULTS: In 493 evaluable patients, the median of days from the first symptom to mammography, biopsy, and surgery was 41, 57, and 92, respectively. The median of days from screening mammography to biopsy and surgery was 10 and 51, respectively. From biopsy to surgery, the median was 34 days in every case. Over the last 5 years, an increase in biopsy-surgery delay has been observed (p = 0.0001). Tumour stages I and II vs. stage III (RR 1.74. 95% CI 1.08-2.80, p = 0.027), diagnosis in screening (RR 0.66. 95% CI 0.45-0.96, p = 0.030), and use of magnetic resonance imaging (RR 2.08. 95 CI 1.21-3.56, p = 0.008) condition a greater biopsy-surgery delay. No influence of delays on survival has been identified. CONCLUSIONS: Delays in diagnosis and surgery in the case of women diagnosed on the basis of symptoms may be improved. There is a temporary tendency to a greater delay in surgery. Some clinical and biological factors must be taken into account to optimise delays. Survival results are not adversely affected by delays.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Diagnóstico Tardio/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
6.
Sci Rep ; 8(1): 4676, 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29535390

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

7.
Sci Rep ; 7(1): 4297, 2017 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-28655910

RESUMO

Charge separation is a critical process for achieving high efficiencies in organic photovoltaic cells. The initial tightly bound excitonic electron-hole pair has to dissociate fast enough in order to avoid photocurrent generation and thus power conversion efficiency loss via geminate recombination. Such process takes place assisted by transitional states that lie between the initial exciton and the free charge state. Due to spin conservation rules these intermediate charge transfer states typically have singlet character. Here we propose a donor-acceptor model for a generic organic photovoltaic cell in which the process of charge separation is modulated by a magnetic field which tunes the energy levels. The impact of a magnetic field is to intensify the generation of charge transfer states with triplet character via inter-system crossing. As the ground state of the system has singlet character, triplet states are recombination-protected, thus leading to a higher probability of successful charge separation. Using the open quantum systems formalism we demonstrate that the population of triplet charge transfer states grows in the presence of a magnetic field, and discuss the impact on carrier population and hence photocurrent, highlighting its potential as a tool for research on charge transfer kinetics in this complex systems.

8.
Nanotechnology ; 27(12): 125301, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-26889870

RESUMO

We have studied the influence of anisotropic nanopatterns (ripples) on the adhesion and morphology of mouse neural stem cells (C17.2) on glass substrates using cell viability assay, optical microscopy and atomic force microscopy. The ripples were produced by defocused ion beam sputtering with inert Ar ions, which physically remove atoms from the surface at the energy of 800 eV. The ripple periodicity (∼200 nm) is comparable to the thickness of the cytoplasmatic microspikes (filopodia) which link the stem cells to the substrate. All methods show that the cell adhesion is significantly lowered compared to the same type of cells on flat glass surfaces. Furthermore, the AFM analysis reveals that the filopodia tend to be trapped parallel or perpendicular to the ripples, which limits the spreading of the stem cell on the rippled substrate. This opens the perspective of controlling the micro-adhesion of stem cells and the orientation of their filopodia by tuning the anisotropic substrate morphology without chemical reactions occurring at the surface.


Assuntos
Nanoestruturas/ultraestrutura , Células-Tronco Neurais/fisiologia , Animais , Anisotropia , Adesão Celular , Sobrevivência Celular , Vidro , Camundongos , Microscopia de Força Atômica , Propriedades de Superfície
9.
Phys Rev E Stat Nonlin Soft Matter Phys ; 74(4 Pt 2): 047101, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17155216

RESUMO

We report experimental evidence of the fact that, in an emerging Rayleigh-Bénard structure, the density of defects which appear scales as a power law in the rate of change of the control parameter. The scaling exponents agree with those calculated from the Kibble-Zurek mechanism. This is the first evidence to our knowledge that this mechanism works in a hydrodynamical system.

10.
J Chem Phys ; 124(4): 044508, 2006 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-16460186

RESUMO

The vibrational spectrum of liquids constituted of chain molecules is difficult to analyze because it may have contributions of different rotational isomers. In turn, with a proper vibrational assignment, this feature allows us to extract information about the effect of temperature or pressure on the molecular conformations in the liquid state. In this regard, the information on the vibrational spectrum in the solid phase greatly simplifies the vibrational analysis of the different rotational conformers existing in the liquid, as the molecules usually present all-trans conformations in the crystalline state. Here we report room-temperature Raman experiments on n-pentanol performed in a sapphire-anvil cell up to 3 GPa. A detailed analysis of the liquid-solid phase transition occurring at 1.3 GPa is provided. The analysis of the Raman spectrum in the solid phase allows the identification of the bands due to the different rotational isomers present in the liquid. The analysis of the spectral region corresponding to skeletal vibrations of the carbon chain (800-1200 cm(-1)) indicates that gauche conformers are promoted by the application of pressure. The analysis of the intensity ratio of those bands assigned to trans and gauge conformations is used to calculate the change in molecular volume ascribed to the trans-gauge isomerization process. We find a value similar to that found in n-alkanes, i.e., -0.88 cm(3) mol(-1). In addition, we find indication that pressure varies the proportions of the different gauge conformers. Thus, it appears that the GTTt to TGTt transition in the carbon chain is favored at high pressures. As expected, a smaller change in the molecular volume accompanies this conformation change.

11.
Kidney Int ; 69(4): 685-90, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16395254

RESUMO

Lead exposure induces dysfunction of the cyclic guanosine monophosphate-dependent vasodilator system through downregulation of soluble guanylate cyclase (sGC) expression. The endothelium not only releases vasodilators but also vasoconstrictors such as endothelin-1 (ET-1). Our aim was to explore the role of the vascular endothelium and ET-1 as possible mediators of lead-induced downregulation of sGC. Isolated aortic segments from Wistar Kyoto rats were incubated in the presence or absence of lead (1 parts per million) for 24 h. Endothelium was mechanically removed in some of the aorta segments. As reported previously, lead exposure induced downregulation of sGC protein expression in the intact aortic segments. However, lead exposure failed to significantly modify sGC-beta1 subunit expression in the endothelium-denuded aortic segments. Incubation with a selective ETA-type receptor inhibitor, BQ-123 (10(-6) mol/l), restored sGC protein expression in lead-exposed intact aortic segments. As it has also been previously observed, incubation in lead-containing medium resulted in the upregulation of cyclooxygenase-2 (COX-2) in the intact aortic segments. Denudation of endothelium partially abrogated this effect of lead. Incubation with BQ-123 prevented the lead-induced upregulation COX-2 in the intact aortic segments. However, neither ET-1 content nor ETA-type receptor expression were modified by lead exposure of the aortic segments. As conclusion, the endothelium through the activation of ETA-type receptors mediates the downregulation of sGC expression by lead in the vascular wall.


Assuntos
Endotelina-1/fisiologia , Endotélio Vascular/fisiopatologia , Chumbo/farmacologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Receptor de Endotelina A/fisiologia , Animais , Anti-Hipertensivos/farmacologia , Aorta , Western Blotting , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/genética , Regulação para Baixo , Antagonistas do Receptor de Endotelina A , Endotelina-1/análise , Endotélio Vascular/química , Guanilato Ciclase/genética , Guanilato Ciclase/metabolismo , Técnicas In Vitro , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Peptídeos Cíclicos/farmacologia , Ratos , Ratos Endogâmicos WKY , Receptor de Endotelina A/análise , Vasodilatação/fisiologia
12.
Toxicol In Vitro ; 19(7): 899-902, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16095870

RESUMO

A variety of aquatic pollutants are able to induce cytochrome P4501A (CYP1A) in fish by ligand binding to the aryl hydrocarbon receptor (AhR). High-affinity AhR ligands are planar aromatic polycyclic molecules such as the prototypical ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The present work investigates the ability of the imidazole derivative, Prochloraz (PRO), to induce CYP1A. Computational studies on the molecular structure of PRO indicated that it is highly unlikely for PRO to have both aromatic rings of the molecule, i.e. the imidazole and the benzene ring, in the same plane. Thus, the possible conformers do not take planar structures, in contrast to the typically planar AhR ligands. Experimentally, the capability of PRO to induce CYP1A was assessed using the rainbow trout liver cell line, RTL-W1, as in vitro model. PRO increased in a concentration-dependent way the catalytic activity of CYP1A (determined as 7-ethoxyresorufin-O-deethylase, EROD, activity) in RTL-W1 cells. The potency of PRO was lower than that of a reference AhR-ligand, beta-naphthoflavone (betaNF). In addition to the catalytic level, PRO activated CYP1A also at the transcriptional level as determined by RT-PCR analysis of CYP1A mRNA. These results indicate that PRO, although its structure is not corresponding to the typical features of CYP1A-inducing AhR ligands, still is able to activate CYP1A expression.


Assuntos
Sistema Enzimático do Citocromo P-450/biossíntese , Fungicidas Industriais/farmacologia , Imidazóis/farmacologia , Animais , Linhagem Celular , Sistema Enzimático do Citocromo P-450/genética , Relação Dose-Resposta a Droga , Indução Enzimática/efeitos dos fármacos , Conformação Molecular , Oncorhynchus mykiss , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , beta-Naftoflavona/farmacologia
13.
Nefrologia ; 23(5): 432-6, 2003.
Artigo em Espanhol | MEDLINE | ID: mdl-14658169

RESUMO

BACKGROUND: Sevelamer is a non-absorbable phosphorus chelator that is not a source of aluminium, calcium or base. The clinical experience with sevelamer in peritoneal dialysis and in daily clinical practice is scarce. The aim of this study is to evaluate the results of therapy of hyperphosphoremia with sevelamer on serum phosphorus and phosphorus chelators requirements, in a peritoneal dialysis clinical practice. METHODS: Sevalamer 400 mg was prescribed to peritoneal dialysis patients with hyperphosphoremia who were treated with aluminium hydroxide or with calcium salts in the absence of hypocalcemia. Fourteen patients completed 12 months of therapy. RESULTS: The initial sevelamer dose was 2,280 +/- 760 mg/day, and was increased to 2,760 +/- 1,160 mg/day at 12 months. At 12 months no patient was on aluminium salts and calcium salts had been significantly reduced. Phosphoremia (5.9 +/- 0.6 to 5.0 +/- 1.4 mg/dL, p = 0.049), calcium-phosphorus product (59.8 +/- 5.8 to 48.6 +/- 12.5 mg2/dL2, p = 0.01) and serum cholesterol (191 +/- 29 to 167 +/- 33 mg/dL, p = 0.02) decreased at 12 months. No significant changes were observed in serum triglycerides, total CO2 or PTH. Serum alkaline phosphatase increased at 6 months, but values returned to normal at 12 months. No changes were observed in serum gamma-glutamyl-transpeptidase. Five patients were started on 1.25 (OH)2 vitamin D therapy. CONCLUSION: In peritoneal dialysis patients, sevelamer allows a satisfactory control of serum phosphorus levels and calcium-phosphorus product, while decreasing the amount of aluminium and calcium salts prescribed.


Assuntos
Compostos de Epóxi/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Diálise Peritoneal/métodos , Distúrbios do Metabolismo do Fósforo/tratamento farmacológico , Polietilenos/uso terapêutico , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Distúrbios do Metabolismo do Fósforo/etiologia , Poliaminas , Estudos Prospectivos , Sevelamer , Resultado do Tratamento
14.
Nefrología (Madr.) ; 23(5): 432-436, 2003.
Artigo em Es | IBECS | ID: ibc-28774

RESUMO

Introducción: El sevelamer es un quelante del fósforo no absorbible que no aporta aluminio, calcio ni bases. La experiencia con este nuevo quelante en nuestro medio, en diálisis peritoneal y en la práctica clínica diaria es escasa. El objetivo de este estudio es evaluar los resultados del tratamiento con sevelamer sobre la fosforemia y el uso de quelantes del fósforo en diálisis peritoneal. Métodos: En los pacientes del programa de diálisis peritoneal que recibían hidróxido de aluminio o que recibían sales de calcio sin tener tendencia a la hipocalcemia, la hiperfosforemia se trató con sevelamer. Catorce pacientes completaron 12 meses de tratamiento. Resultados: La dosis inicial de sevelamer fue de 2.280 ñ 760 mg/día, repartidos en dos o tres dosis y a los 12 meses era 2.760 ñ 1.160 mg/día. A los 12 meses el hidróxido de aluminio se había suspendido y la dosis de sales de calcio, la fosforemia (5,9 ñ 0,6 a 5,0 ñ 1,4 mg/dL, p = 0,049), el producto calciofósforo (59,8 ñ 5,8 a 48,6 ñ 12,5 mg2/dL2, p = 0,01) y el colesterol (191 ñ 29 a 167 ñ 33 mg/dL, p = 0,02) disminuyeron. No hubo cambios significativos en los triglicéridos, CO2 total ni la PTH. Se objetivó un aumento de la fosfatasa alcalina a los 6 meses, que se había normalizado a los 12 meses, sin cambios en la GGTY. Cinco pacientes comenzaron tratamiento con 1,25 dihidroxivitamina D. Conclusiones: En diálisis peritoneal el sevelamer permite un adecuado control de la fosforemia, a pesar de un menor uso de sales de calcio y de aluminio, y mejora el producto calcio-fósforo (AU)


Assuntos
Pessoa de Meia-Idade , Masculino , Feminino , Humanos , Resultado do Tratamento , Polietilenos , Diálise Peritoneal , Distúrbios do Metabolismo do Fósforo , Estudos Prospectivos , Insuficiência Renal Crônica , Compostos de Epóxi
15.
Hypertension ; 38(6): 1400-5, 2001 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11751725

RESUMO

Heart failure is characterized by neurohumoral alterations, such as activation of the sympathetic nervous system, stimulation of the renin-angiotensin system, increased activity of the endothelin system, increased production of norepinephrine, and increased circulating levels of cytokines. Oxidative stress is associated with the formation of reactive oxygen species (ROS). The myocardium has enzymes that stimulate ROS generation and enzymes with antioxidant effects. Several studies have suggested that ROS are increased in the failing heart. ROS may contribute to the pathophysiology of heart failure by initiating myocyte apoptosis and exerting direct negatively inotropic effects through the reduction of cytosolic intracellular free calcium. However, mechanisms such as endothelial dysfunction and inflammation have also been involved in the progression of heart failure. Antioxidants (eg, vitamin C) seem to improve endothelial functionality and reduce the inflammatory response in patients with heart failure. Therefore, in this review, we analyzed the involvement of ROS in the cellular and molecular mechanisms associated with endothelial dysfunction in heart failure.


Assuntos
Endotélio Vascular/metabolismo , Insuficiência Cardíaca/fisiopatologia , Animais , Fármacos Cardiovasculares/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Miocárdio/metabolismo , Ativação de Neutrófilo , Óxido Nítrico Sintase/genética , Oxirredução , Estresse Oxidativo , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo
16.
Hypertension ; 38(4): 907-12, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11641307

RESUMO

Data remain insufficient to place the decreased response to L-arginine in hypertensive patients within a consistent pathophysiological sequence. The aim of the present study in patients with essential hypertension was to assess the relationships between the response to L-arginine and a set of relevant clinical and laboratory parameters. In this prospective, interventional study, we administered L-arginine to untreated hypertensive individuals and healthy control subjects and measured the clearance of inulin and of para-aminohippurate and a set of biochemical and clinical variables. L-Arginine infusion revealed major differences between control subjects and 1 subgroup (group B) of hypertensive individuals. Group B hypertensives (n=18) had no increase in inulin clearance and no decrease in renal vascular resistance with L-arginine; however, in another subset of hypertensive patients (group A, n=27), the insulin clearance increased and renal vascular resistance decreased similar to the control group (group C, n=11). The ambulatory blood pressure monitoring in group B showed both an increased mean diastolic pressure and a "nondipper" pattern in the nocturnal regulation of arterial pressure. These findings in group B were accompanied by significant alterations in optic fundus and left ventricle hypertrophy and increased microalbuminuria (all, P<0.05). Furthermore, group B individuals had significantly lower values of HDL cholesterol and a higher baseline atherogenic index, plasma insulin level, and glucose/insulin index. We disclose a previously undescribed relationship between end organ repercussion and decreased renal hemodynamic response to L-arginine. Our results may help to understand the mechanisms that lead to target organ damage in hypertension.


Assuntos
Arginina/farmacologia , Hipertensão/fisiopatologia , Rim/irrigação sanguínea , Vasodilatação/efeitos dos fármacos , Adulto , Albuminúria/urina , Pressão Sanguínea/efeitos dos fármacos , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , Eletrocardiografia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão/metabolismo , Inulina/sangue , Inulina/farmacocinética , Masculino , Pessoa de Meia-Idade , Circulação Renal/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos , Ácido p-Aminoipúrico/sangue , Ácido p-Aminoipúrico/farmacocinética
17.
Nephrol Dial Transplant ; 16(11): 2188-93, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11682666

RESUMO

BACKGROUND: Recent data have suggested the existence of a relationship between the use of synthetic vascular accesses and increased erythropoietin (Epo) requirements. The present study aimed to evaluate the possible role of the type of vascular access in both Epo and intravenous (i.v.) iron requirements. METHODS: One-hundred-and-seven individuals without recognized causes of Epo resistance, 62 of them undergoing chronic haemodialysis through native arteriovenous fistulae (AVF) and 45 through PTFE grafts, were retrospectively studied (one-year follow-up). Sixty-nine patients, i.e. all but three with a PTFE graft and 27 with native AVF, were taking anti-platelet agents. Doses of i.v. iron and Epo and laboratory parameters were recorded. RESULTS: Erythropoietin and i.v. iron requirements were higher in the patients dialysed through PTFE grafts compared with those with native AVF (Epo: 103.8+/-58.4 vs 81.0+/-44.5 U/kg/week, P=0.025; i.v. iron: 178.9+/-111 vs. 125.9+/-96 mg/month, P=0.01). On a yearly basis, the difference in Epo dose represented a total of 94582+/-16789 U Epo/patient/year. Moreover, the patients with PTFE grafts received more red blood cell transfusions than patients with native AVF (P=0.021). No differences between laboratory, dialysis kinetics, demographic or comorbidity parameters were found. The type of vascular access was the best predictor of the requirement of > or =150 U/kg/week Epo (P=0.03). Even though the patients who received anti-platelet therapy required more i.v. iron (167.5+/-103.6 vs. 114.5+/-101.4 mg/month, P=0.008) but not more Epo (P=NS), the possibility of an accessory role of anti-platelet agents in the increased Epo requirements with PTFE grafts cannot be ruled out. CONCLUSIONS: The use of a PTFE graft and anti-platelet drugs represents a previously undescribed association related to higher Epo and i.v. iron requirements. The association described herein adds new arguments to the debate concerning the choice of vascular access in chronic haemodialysis patients.


Assuntos
Prótese Vascular , Eritropoetina/uso terapêutico , Ferro/uso terapêutico , Diálise Renal , Idoso , Derivação Arteriovenosa Cirúrgica , Humanos , Injeções Intravenosas , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Politetrafluoretileno
18.
Circulation ; 104(15): 1822-30, 2001 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-11591621

RESUMO

BACKGROUND: We recently obtained evidence demonstrating that cultured bovine endothelial cells contain cytosolic proteins that form complexes with the 3'-untranslated region of endothelial nitric oxide synthase (eNOS) mRNA and are associated with its destabilization. The aim of this study was to determine the presence of such proteins and eNOS expression in hypercholesterolemic rabbits as an in vivo model of endothelial dysfunction. METHODS AND RESULTS: Endothelium-dependent relaxation to acetylcholine and the calcium ionophore A23187 was reduced in aortic segments from hypercholesterolemic rabbits compared with controls. Treatment of hypercholesterolemic rabbits with cerivastatin (0.1 mg. kg body wt(-1). d(-1)) restored endothelium-dependent relaxation. Aortic eNOS expression was reduced in hypercholesterolemic rabbits and was accompanied by enhanced binding activity of a 60-kDa cytosolic protein and reduced stability of eNOS mRNA. Cerivastatin treatment upregulated eNOS expression and reduced the interaction of the cytosolic protein with the 3'-untranslated region of eNOS mRNA. Mononuclear cells from hypercholesterolemic rabbits also showed a marked reduction of eNOS expression and eNOS mRNA stability and an increase in binding activity of the cytosolic protein, which were also prevented by cerivastatin treatment. CONCLUSIONS: These results demonstrate the presence of a 60-kDa protein that binds to eNOS mRNA and reductions in eNOS expression in both vascular wall and mononuclear cells that are prevented by cerivastatin.


Assuntos
Regulação da Expressão Gênica , Hipercolesterolemia/fisiopatologia , Leucócitos Mononucleares/enzimologia , Óxido Nítrico Sintase/metabolismo , Piridinas/farmacologia , Regiões 3' não Traduzidas/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Citosol/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipercolesterolemia/tratamento farmacológico , Técnicas In Vitro , Ionóforos/farmacologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Substâncias Macromoleculares , Masculino , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo III , Ligação Proteica/efeitos dos fármacos , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/metabolismo , Coelhos , Especificidade por Substrato , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
19.
Rev Esp Cardiol ; 54(7): 880-6, 2001 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-11446964

RESUMO

BACKGROUND: Although different studies have evaluated the ability of endothelial cells to produce NO in the setting of the endothelial dysfunction associated with hypertension, less it is known about the soluble guanylate cyclase system. AIM: To analyze the level of expression of sGC in the vascular wall in Stroke-prone spontaneously hypertensive rats (SHRSP). Moreover, the effect of treatment with an alpha1 adrenergic antagonist, doxazosin, on sGC expression was also evaluated. METHODS: The study was performed in 24 untreated 20-week-old SPSHR and 12 SPSHR treated orally with doxazosin (10 mg/Kg bw/day; for 15 days). A group of normotensive Wistar-Kyoto (WKY) rats were used as controls (n = 12). RESULTS: Isolated aortic segments from SHRSP showed impaired response to SNP. Doxazosin treatment prevented impaired vasodilatory response to SNP. Expression of the beta1 sGC in the vascular wall of SHRSP determined by Western blot and immunohistochemistry was markedly reduced with respect to that of WKY. Doxazosin treatment increased of beta1 sGC expression in treated SHRSP particularly at the medium level with respect to that of untreated SHRSP. CONCLUSION: SHRSP showed reduced expression of beta1 sGC in the vascular wall and an impaired vasodilator response to SNP which improved with doxazosin treatment. These results suggest the role the sGC system may play in the global treatment of endothelial dysfunction.


Assuntos
Anti-Hipertensivos/uso terapêutico , Modelos Animais de Doenças , Doxazossina/uso terapêutico , Guanilato Ciclase/biossíntese , Hipertensão/tratamento farmacológico , Animais , Pressão Sanguínea/efeitos dos fármacos , Masculino , Nitroprussiato/farmacologia , Ratos , Ratos Endogâmicos SHR , Vasodilatadores/farmacologia
20.
Phys Rev E Stat Nonlin Soft Matter Phys ; 63(5 Pt 2): 057301, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11415050

RESUMO

We report experimental evidence of the fact that, in a Bénard-Marangoni conduction-convection transition, the density of defects in the emerging structure scales as a power law in the quench time needed for the control parameter to ramp through the threshold. The obtained scaling exponents differ from the ones predicted and observed in the case in which the defects correspond to zeros in the amplitude of the global two-dimensional field.

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