RESUMEN
Estrogens reduce 0.3 M NaCl intake and palatability in a widely used model of essential hypertension, the spontaneously hypertensive rats (SHRs). Here we investigated whether the inhibitory effects of ß-estradiol (E2, 10 µg/kg b.w. subcutaneously for 8 days) on water deprived partially-rehydrated (WD-PR) ovariectomized (OVX) adult female SHRs (fSHRs, n = 4-10/group) are related to interferences on brain angiotensin II AT1 receptors (AT1r). After WD-PR, E2 reduced 0.3 M NaCl intake (1.3 ± 0.6, vs. vehicle: 3.5 ± 1.2 ml/30 min), the number of hedonic responses to intraoral NaCl infusion (57 ± 11, vs. vehicle: 176 ± 32/min), and the relative angiotensin AT1r (Agtr1a) mRNA expression in the hypothalamus. Losartan (AT1r antagonist, 100 µg) intracerebroventricularly in OVX fSHRs treated with vehicle subcutaneously abolished 0.3 M NaCl intake (0.1 ± 0.1 ml/30 min) and only transiently reduced hedonic responses to intraoral NaCl. Losartan combined with E2 decreased the number of hedonic and increased the number of aversive responses to intraoral NaCl and abolished 0.3 M NaCl intake. E2 also reduced the pressor and dipsogenic responses to intracerebroventricular angiotensin II. The results suggest that AT1r activation increases palatability and induces NaCl intake in WD-PR fSHRs. E2 reduced hypothalamic Agtr1a mRNA expression, which may account for the effects of E2 on NaCl intake and palatability and intracerebroventricular angiotensin II-induced pressor and dipsogenic responses in OVX fSHRs. Future studies considering natural fluctuations in estrogen secretion might help to determine the degree of such interference in brain neuronal activity.
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Angiotensina II , Losartán , Angiotensina II/farmacología , Animales , Estradiol/farmacología , Femenino , Humanos , Losartán/farmacología , ARN Mensajero , Ratas , Ratas Endogámicas SHR , Receptor de Angiotensina Tipo 1/genética , Cloruro de SodioRESUMEN
Spontaneously hypertensive rats (SHRs) ingest more NaCl than normotensive strains. Here we investigated NaCl intake and taste reactivity in adult male SHRs and normotensive Holtzman rats treated or not with AT1 receptor antagonist centrally in euhydrated condition and after fluid depletion. Taste reactivity was measured by the number of orofacial expressions to intra-oral infusions of 0.3 M NaCl. In euhydrated condition, intra-oral infusions of 0.3 M NaCl produced greater number of hedonic responses in SHRs than in normotensive rats, without differences in the number of aversive responses. Compared to euhydrated condition, the treatment with the diuretic furosemide + low dose of captopril (angiotensin converting enzyme blocker) increased the number of hedonic and reduced the number of aversive responses to intra-oral NaCl in normotensive rats, without changing the number of hedonic or aversive responses in SHRs. Losartan (AT1 receptor antagonist, 100 ng/1 µl) injected intracerebroventricularly in SHRs abolished 0.3 M NaCl intake induced by water deprivation + partial rehydration, whereas only transiently (first 30 min of the 60 min test) reduced hedonic responses, without changes in aversive responses to intra-oral NaCl. Losartan intracerebroventricularly also only transiently (first 30 min) reduced the number of hedonic responses to intra-oral NaCl in euhydrated SHRs. The results suggest that NaCl palatability is increased and independent from body fluid balance in SHRs. The results also suggest that central AT1 receptors are part of the mechanisms activated to increase NaCl intake and palatability in SHRs. A partial dissociation between NaCl intake and palatability in SHRs is also suggested.
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Captopril , Sodio , Animales , Captopril/farmacología , Furosemida/farmacología , Losartán/farmacología , Masculino , Ratas , Ratas Endogámicas SHRRESUMEN
The renin-angiotensin system (RAS) controls hypertonic NaCl intake driven by sodium appetite. Here we investigated whether the antagonism of RAS interferes with hedonic and aversive orofacial motor responses, or palatability, to intraoral infusion of 0.3 M NaCl (hNaCl). Adult rats were depleted of sodium by combined sc injection of furosemide and 24 h removal of ambient sodium. In experiment 1, losartan (AT1 angiotensin II receptor antagonist, intracerebroventricular, 200 µg/µl), produced a three-fold increase in aversive orofacial motor responses to hNaCl. Losartan also suppressed hNaCl intake recorded immediately thereafter. In experiment 2, each animal had repeated recordings of hNaCl intake and orofacial responses to hNaCl distributed for 180 min. Paired recordings of intake and orofacial responses occurred within five successive blocks after the recordings of only orofacial responses when the animals were still sodium deplete (block zero). Captopril (angiotensin converting enzyme blocker, intraperitoneal, 30 mg/kg) inhibited by 75% the hedonic orofacial responses to hNaCl in blocks zero and 1. The hedonic responses to captopril remained the same throughout blocks, but became similar to vehicle from blocks 2 to 5. There was no difference in aversive responses to 0.3 M NaCl between captopril and vehicle. Captopril produced a 70-100% inhibition of hNaCl intake in blocks 1 to 5. The results suggest that angiotensin II acts in the brain increasing the palatability of hypertonic sodium during the consummatory phase of sodium appetite.
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Sistema Renina-Angiotensina , Sodio , Animales , Apetito , Captopril/farmacología , Losartán/farmacología , Ratas , Cloruro de SodioRESUMEN
Behavioral sensitization occurs during sodium appetite (expressed as sodium intake to compensate for depleted sodium) and need-free sodium intake (expressed as daily overnight sodium intake in excess of dietary sodium need). Previously, we found that a slow-onset sodium appetite protocol cross-sensitized need-free sucrose intake in sucrose-naïve adult rats. That is, a history of sodium depletion elevated later sucrose intake. The objective of the present work was, first, to investigate whether a protocol that evokes a rapid-onset (within 2 h) sodium appetite using furosemide along with a low dose captopril (Furo/Cap), also cross-sensitizes sucrose intake. Then, we investigated whether 1) sensitization of need-free 0.3 M NaCl intake interacts with need-free sucrose intake, and 2) MK-801, a glutamate NMDA receptor antagonist, inhibits cross-sensitization of sucrose intake. Groups received 3-4 Furo/Cap or vehicle treatments with 48/72-h intervals. We investigated sucrose intake in hydrated and fed conditions for 2 h/day for 5 days, starting 6-10 days after the last Furo/Cap treatment. Episodes of Furo/Cap sensitized need-free sodium intake, as expected. Similar to our prior work, the rapid-onset Furo/Cap protocol cross-sensitized sucrose intake in sucrose-naïve rats and had no persistent effect on blood biochemistry. MK-801 treatment along with Furo/Cap injections appeared to prevent cross-sensitization of sucrose consumption. Sucrose intake tests unexpectedly reduced sensitized need-free sodium intake. However, MK-801 treatment allowed a rebound in need-free sodium intake subsequent to the last sucrose intake test. The results suggest that plasticity in glutamatergic mechanisms mediate inverse and reciprocal interactions between the production of sodium appetite and sucrose intake.
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Apetito , Sodio en la Dieta , Animales , Diuréticos/farmacología , Ratas , Ratas Sprague-Dawley , Sodio , AzúcaresRESUMEN
OBJECTIVE: Studies have been conducted to determine the causal factors and clinical consequences of non-adherence to treatment in systemic lupus erythematosus (SLE). However, no interventions have been performed to increase drug adherence. Our objective was to assess the effectiveness of pharmaceutical care (PC) for drug treatment adherence in lupus nephritis (LN). METHODS: This was a randomized clinical trial (pragmatic trial) in patients with LN in Rio de Janeiro, Brazil, allocated in two groups: an intervention group (Dader Method for PC) and a control group (institution's usual care). Drug treatment adherence was measured by the combination of five questions normally used in clinical practice. RESULTS: A total of 131 patients were randomized, and 122 completed the study, with a mean follow-up of 12.7 months and use of six drugs per day and 10-12 doses per day. Low adherence was observed at baseline (intervention group: 30%; control group: 29%). PC showed 27% effectiveness (95% confidence interval (CI) -6% to 50%) in the intention to treat analysis and 31% (95% CI 0-52%) in per protocol analysis, considering all drugs. As for adherence to specific drugs for SLE, effectiveness of PC was 64% (95% CI 34-80%) with intention-to-treat analysis and 62% (95% CI 32-79%) in per protocol analysis. CONCLUSIONS: PC was effective for increasing drug treatment adherence in SLE. The detailed account provided by the Dader Method of the difficulties with patients' drug therapy proved invaluable to approach non-adherence.
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Nefritis Lúpica/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Servicios Farmacéuticos/organización & administración , Adulto , Brasil , Femenino , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Excessive salt intake has been associated with the development or worsening of chronic diseases such as hypertension and spontaneously hypertensive rats (SHR) have a typical increased sodium preference. Estrogens reduce sodium appetite, but we do not know whether such effect relates to alterations in sodium palatability. Here we evaluated the influence of ovarian hormones on orofacial motor responses, an index of palatability, to intra-oral infusion of 0.3â¯M NaCl (IONaCl). Adult female SHR and normotensive Holtzman rats (HTZ) were used. Sodium appetite was produced by water deprivation followed immediately by partial rehydration by drinking water to satiation (WD-PR protocol). Immediately at the end of WD-PR, animals received an IO-NaCl for videotape recording of orofacial motor responses. At the end of IO-NaCl, they had access to two bottles containing 0.3â¯M NaCl and water to ingest (sodium appetite test). Bilateral ovariectomy (OVX) enhanced 0.3â¯M NaCl intake during the sodium appetite test and increased the frequency of orofacial hedonic responses to IO-NaCl in both strains. It had no effect on aversive responses. Estradiol treatment in SHR-OVX decreased hedonic responses and increased aversive responses to IO-NaCl. It also reduced 0.3â¯M NaCl intake during the sodium appetite test, but had no effect on baseline mean arterial pressure and heart rate. The results suggest that ovarian hormones restrain WD-PR-induced sodium appetite by reducing the hedonic properties of sodium taste. The results also suggest that estrogens mediate such reduction, particularly in SHR.
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Estradiol/farmacología , Cloruro de Sodio/administración & dosificación , Privación de Agua , Animales , Femenino , Ovariectomía , Distribución Aleatoria , Ratas Endogámicas SHR , Ratas Sprague-Dawley , Gusto/fisiologíaRESUMEN
It is of current interest the identification of appropriate matrices for growing mesenchymal stem cells (MSC). These cells are able not only to regenerate themselves but also to differentiate into other type of functional cells, and so they have been extensively used in tissue engineering. In this work, we have evaluated the use of electric impedance spectroscopy (EIS) to follow the adhesion of MSC from Wharton's jelly of the human umbilical cord (hWJMSC) on sugarcane biopolymers (SCB). Impedance spectra of the systems were obtained in the frequency range of 10(2)-10(5) Hz. An EIS investigation showed that when deposited on a metallic electrode SCB films prevent the passage of electrons between the solution and the metallic interface. The impedance spectra of hWJMSCs adhered on SCB revealed that there is a significant increase in the magnitude of the impedance when compared to that of pure SCB. The corresponding resistance (real part of the impedance) was even higher for the SCB-hWJMSC system than for SCB without cells on their surface, in an indication of an increased blockage to the electron transfers. The resistance charge transfer is extracted by curve-fitting the impedance spectra to an equivalent circuit model. Also, a shift of the phase angle to higher frequencies was obtained for SCB-hWJMSC system as a result from hWJMSC adhesion. Our study demonstrates that EIS is an appropriate method to evaluate the adhesion of MSC. SCB can be considered as a promising biomaterial for tissue engineering.
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Materiales Biocompatibles/química , Biopolímeros/química , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Saccharum/química , Cordón Umbilical/citología , Adhesión Celular , Células Cultivadas , Impedancia Eléctrica , Femenino , Humanos , Ensayo de Materiales , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Embarazo , Ingeniería de Tejidos , Gelatina de Wharton/citologíaRESUMEN
Spontaneously hypertensive rats (SHRs) have increased daily or induced sodium intake compared to normotensive rats. In normotensive rats, angiotensin II (ANG II)-induced sodium intake is blocked by the inactivation of p42/44 mitogen-activated protein kinase, also known as extracellular signal-regulated protein kinase1/2 (ERK1/2). Here we investigated if inhibition of ERK1/2 pathway centrally would change sodium appetite and intracerebroventricular (icv) ANG II-induced pressor response in SHRs. SHRs (280-330 g, n = 07-14/group) with stainless steel cannulas implanted in the lateral ventricle (LV) were used. Water and 0.3 M NaCl intake was induced by the treatment with the diuretic furosemide + captopril (angiotensin converting enzyme blocker) subcutaneously or 24 h of water deprivation (WD) followed by 2 h of partial rehydration with only water (PR). The blockade of ERK1/2 activation with icv injections of U0126 (MEK1/2 inhibitor, 2 mM; 2 µl) reduced 0.3 M NaCl intake induced by furosemide + captopril (5.0 ± 1.0, vs. vehicle: 7.3 ± 0.7 mL/120 min) or WD-PR (4.6 ± 1.3, vs. vehicle: 10.3 ± 1.4 mL/120 min). PEP7 (selective inhibitor of AT1 receptor-mediated ERK1/2 activation, 2 nmol/2 µL) icv also reduced WD-PR-induced 0.3 M NaCl (2.8 ± 0.7, vs. vehicle: 6.8 ± 1.4 mL/120 min). WD-PR-induced water intake was also reduced by U0126 or PEP7. In addition, U0126 or PEP7 icv reduced the pressor response to icv ANG II. Therefore, the present results suggest that central AT1 receptor-mediated ERK1/2 activation is part of the mechanisms involved in sodium appetite and ANG II-induced pressor response in SHRs.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Angiotensina II/genética , Apetito/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Receptor de Angiotensina Tipo 1/genética , Animales , Apetito/genética , Butadienos/farmacología , Captopril/farmacología , Modelos Animales de Enfermedad , Furosemida/farmacología , Humanos , Hipertensión/genética , Hipertensión/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Nitrilos/farmacología , Ratas , Ratas Endogámicas SHR , Sodio/metabolismoRESUMEN
Muscle cellularity was studied in Pagellus bogaraveo juveniles fed on diets with different protein contents. Measured in transversal body sections, at both post-opercular and post-anal locations, the morphometric variables estimated were: total muscle area (A), total number of fibres (N), number of fibres per unit area of muscle (N (A)) and cross-sectional fibre area (a) of the two main muscle fibre types. At the end of the experiment fish fed on diets having more than 40% of protein displayed significantly higher body weight. Fish fed on protein-rich diets exhibited greater a and N. For fish fed on 30 and 50% protein diets the morphometric parameters measured grew linearly with the fish weight. High-protein diets favoured muscle hyperplasia. When comparing rostral and caudal locations, a greater N and a smaller a of posterior red fibres were the consistent differences found-a fact, to our knowledge, so far unreported for fish.
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Fenómenos Fisiológicos Nutricionales de los Animales , Proteínas en la Dieta/administración & dosificación , Desarrollo de Músculos , Fibras Musculares Esqueléticas/efectos de los fármacos , Perciformes/anatomía & histología , Perciformes/crecimiento & desarrollo , Animales , Tamaño Corporal , Fibras Musculares de Contracción Rápida/citología , Fibras Musculares de Contracción Rápida/efectos de los fármacos , Fibras Musculares Esqueléticas/citología , Fibras Musculares de Contracción Lenta/citología , Fibras Musculares de Contracción Lenta/efectos de los fármacosRESUMEN
AIMS: The aim of this work was to analyse the antimicrobial properties of a purified lectin from Eugenia uniflora L. seeds. METHODS AND RESULTS: The E. uniflora lectin (EuniSL) was isolated from the seed extract and purified by ion-exchange chromatography in DEAE-Sephadex with a purification factor of 11.68. The purified lectin showed a single band on denaturing electrophoresis, with a molecular mass of 67 kDa. EuniSL agglutinated rabbit and human erythrocytes with a higher specificity for rabbit erythrocytes. The haemagglutination was not inhibited by the tested carbohydrates but glycoproteins exerted a strong inhibitory action. The lectin proved to be thermo resistant with the highest stability at pH 6.5 and divalent ions did not affect its activity. EuniSL demonstrated a remarkable nonselective antibacterial activity. EuniSL strongly inhibited the growth of Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella sp. with a minimum inhibitory concentration (MIC) of 1.5 microg ml(-1), and moderately inhibited the growth of Bacillus subtilis, Streptococcus sp. and Escherichia coli with a MIC of 16.5 microg ml(-1). CONCLUSIONS: EuniSL was found to be effective against bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The strong antibacterial activity of the studied lectin indicates a high potential for clinical microbiology and therapeutic applications.
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Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Lectinas , Semillas/química , Syzygium/química , Hemaglutinación , Pruebas de Inhibición de Hemaglutinación , Humanos , Lectinas/química , Lectinas/aislamiento & purificación , Lectinas/metabolismo , Lectinas/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
We report an electrical impedance spectroscopy (EIS) characterization of composite systems formed by emulsion polymerization of polypyrrole (PPY) in concentrated aqueous solutions of sodium dodecyl sulfate (SDS) containing dispersed magnetite particles. SDS-(Fe3O4)-(conducting polymer) microaggregates with different iron contents were prepared by varying in a reciprocal manner the relative amounts of the metal oxide and PPY. We have measured the zeta-potential and the average size of the corresponding dispersed particles and examined their relative composition through energy dispersive X-ray (EDX) microanalysis and Fourier transform infrared (FTIR) spectroscopy. Important aspects of the charge transport in these composite particles can be identified by mapping the real and imaginary parts of their complex impedance as a function of the frequency of the applied external electric field. For instance, for binary composites SDS-(Fe3O4) polarization effects are dominant at the low-frequency regime, with a well-defined dielectric relaxation easily identifiable. On the other hand, when the relative amount of PPY is progressively increased in the ternary SDS-(Fe3O4)-PPY composites, a transition between different charge transport mechanisms is observed at higher frequencies. The EIS results suggest that in these ternary aggregates the PPY chains envelop the metal oxide clusters and effectively shield them from the external field, and that only in binary samples that do not contain PPY is that the surfactant molecules can directly enclose the magnetite particles. These results are consistent with the fact that the average size of the aggregates in the ternary composites is in general larger than those of either SDS-PPY or SDS-magnetite binary particles.
RESUMEN
The inhibition of sodium intake by increased plasma osmolarity may depend on inhibitory mechanisms present in the lateral parabrachial nucleus. Activation of alpha(2)-adrenergic receptors in the lateral parabrachial nucleus is suggested to deactivate inhibitory mechanisms present in this area increasing fluid depletion-induced 0.3 M NaCl intake. Considering the possibility that lateral parabrachial nucleus inhibitory mechanisms are activated and restrain sodium intake in animals with increased plasma osmolarity, in the present study we investigated the effects on water and 0.3 M NaCl intake produced by the activation of alpha(2)-adrenergic receptors in the lateral parabrachial nucleus in rats with increased plasma osmolarity. Male Holtzman rats with stainless steel cannulas implanted bilaterally into the lateral parabrachial nucleus were used. One hour after intragastric 2 M NaCl load (2 ml), bilateral injections of moxonidine (alpha(2)-adrenergic/imidazoline receptor agonist, 0.5 nmol/0.2 microl, n=10) into the lateral parabrachial nucleus induced a strong ingestion of 0.3 M NaCl intake (19.1+/-5.5 ml/2 h vs. vehicle: 1.8+/-0.6 ml/2 h), without changing water intake (15.8+/-3.0 ml/2 h vs. vehicle: 9.3+/-2.0 ml/2 h). However, moxonidine into the lateral parabrachial nucleus in satiated rats not treated with 2 M NaCl produced no change on 0.3 M NaCl intake. The pre-treatment with RX 821002 (alpha(2)-adrenergic receptor antagonist, 20 nmol/0.2 microl) into the lateral parabrachial nucleus almost abolished the effects of moxonidine on 0.3 M NaCl intake (4.7+/-3.4 ml/2 h). The present results suggest that alpha(2)-adrenergic receptor activation in the lateral parabrachial nucleus blocks inhibitory mechanisms, thereby allowing ingestion of hypertonic NaCl under conditions of extracellular hyperosmolarity. We suggest that during cell dehydration, circuits subserving sodium appetite are activated, but at the same time strongly inhibited through the lateral parabrachial nucleus.
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Conducta de Ingestión de Líquido/fisiología , Bulbo Raquídeo/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Cloruro de Sodio Dietético/metabolismo , Antagonistas Adrenérgicos alfa/farmacología , Animales , Antihipertensivos/farmacología , Conducta Animal , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Líquidos/fisiología , Conducta de Ingestión de Líquido/efectos de los fármacos , Interacciones Farmacológicas , Idazoxan/análogos & derivados , Idazoxan/farmacología , Imidazoles/farmacología , Masculino , Bulbo Raquídeo/efectos de los fármacos , Inhibición Neural/efectos de los fármacos , Inhibición Neural/fisiología , Ratas , Factores de TiempoRESUMEN
The lateral parabrachial nucleus (LPBN) exerts an important inhibitory influence for the control of sodium and water intake. However, the importance of LPBN on renal responses and cardiovascular changes during extracellular dehydration are still unknown. Here we investigated the effects of bilateral injections of moxonidine (alpha2-adrenergic and imidazoline receptor agonist) on renal and cardiovascular changes in fluid-depleted rats. Male Wistar rats (n=4-8 per group) with bilateral stainless steel guide-cannulas implanted into the LPBN were treated with subcutaneous furosemide (10mg/kg)+captopril (5mg/kg) to induce fluid depletion. Forty-five min later vehicle or moxonidine (0.5nmol/0.2µl) were bilaterally injected into the LPBN. In fluid-depleted rats, moxonidine produced strong 0.3M NaCl and water intake without noticeable changes in cardiovascular parameters. Moxonidine did not change sodium excretion (488±135, vs. vehicle: 376±75µEq/1h) or urinary volume (2.5±0.7, vs. vehicle: 2.5±0.3ml/1h) in fluid-depleted rats without access to fluids for rehydration. However, moxonidine decreased natriuresis (462±127, vs. vehicle: 888±122µEq/1h) and diuresis (2.5±0.5, vs. vehicle: 4.5±0.5ml/1h) in fluid-depleted rats submitted to i.g. rehydration. These data suggest that alpha2-adrenergic mechanism of the LPBN facilitates sodium/water retention and body fluid volume expansion during extracellular dehydration.
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Deshidratación/fisiopatología , Núcleos Parabraquiales/fisiología , Sodio/fisiología , Equilibrio Hidroelectrolítico , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Líquidos Corporales/fisiología , Deshidratación/orina , Diuréticos/farmacología , Ingestión de Líquidos , Furosemida/farmacología , Receptores de Imidazolina/agonistas , Masculino , Natriuresis , Ratas Wistar , Sodio/orina , OrinaRESUMEN
Alpha2-adrenergic, gabaergic or opioidergic activation in the lateral parabrachial nucleus (LPBN) increases sodium intake. In the present study, we investigated the effects of single or combined blockade of opioidergic and gabaergic receptors in the LPBN on the increase of 0.3M NaCl intake induced by α2-adrenoceptor activation in the LPBN. Male Holtzman rats (n=5-9/group) with cannulas implanted bilaterally in the LPBN were treated with the diuretic furosemide (10 mg/kg b wt.) combined with low dose of the angiotensin converting enzyme inhibitor captopril (5 mg/kg b wt.) subcutaneously. Bilateral injections of moxonidine (alpha2-adrenergic/imidazoline receptor agonist, 0.5 nmol) into the LPBN increased furosemide+captopril-induced 0.3M NaCl intake (25.8±1.4, vs. vehicle: 3.8±1.1 ml/60 min). The opioidergic receptor antagonist naloxone (100 nmol) or the GABAA receptor antagonist bicuculline (5 nmol) injected into the LPBN partially reduced the increase of 0.3M NaCl intake produced by LPBN moxonidine (11.8±4.0 and 22.8±4.5, respectively, vs. vehicle+moxonidine: 31.6±4.0 ml/60 min, respectively). Similar to the treatment with each antagonist alone, the combined injections of naloxone (100 nmol) and bicuculline (5 nmol) into the LPBN also partially reduced moxonidine effects on 0.3M NaCl intake (15.5±6.5 ml/60 min). The GABAB receptor antagonist saclofen (5 nmol) injected into the LPBN did not change the effects of moxonidine on 0.3M NaCl intake (24.3±7.8 ml/120 min). These results suggest that the increase of 0.3M NaCl intake by α2-adrenergic receptor activation in the LPBN is partially dependent on GABAA and opioid receptor activation in this area.
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Núcleos Parabraquiales/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Receptores de GABA/metabolismo , Receptores Opioides/metabolismo , Cloruro de Sodio/metabolismo , Animales , Antihipertensivos/farmacología , Baclofeno/farmacología , Bicuculina/farmacología , Captopril/farmacología , Inhibidores Enzimáticos/farmacología , Furosemida/farmacología , Antagonistas de Receptores de GABA-A/farmacología , Agonistas de Receptores GABA-B/farmacología , Imidazoles/farmacología , Masculino , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Núcleos Parabraquiales/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/farmacologíaRESUMEN
The administration of cholinergic agonists like pilocarpine intraperitoneally (i.p.) or carbachol intracerebroventricularly (i.c.v.) induces water, but non significant hypertonic NaCl intake. These treatments also produce pressor responses, which may inhibit sodium intake. Noradrenaline (NOR) acting on α2-adrenoceptors in the lateral parabrachial nucleus (LPBN) deactivates inhibitory mechanisms increasing fluid depletion-induced sodium intake. In the present study, we investigated: (1) water and 1.8% NaCl intake in rats treated with pilocarpine i.p. or carbachol i.c.v. combined with NOR into the LPBN; (2) if inhibitory signals from cardiovascular receptors are blocked by NOR in the LPBN. Male Holtzman rats with stainless steel guide-cannulas implanted in the lateral ventricle and bilaterally in the LPBN were used. Bilateral injections of NOR (80nmol/0.2µl) into the LPBN decreased water intake (0.8±0.3, vs. saline (SAL): 2.9±0.3ml/180min) induced by pilocarpine (1mg/kg of body weight) i.p., without changing 1.8% NaCl intake (0.8±2.4, vs. SAL: 0.5±0.3ml/180min). Prazosin (1mg/kg of body weight) i.p. blocked pressor responses and increased water and 1.8% NaCl intake (6.3±1.7 and 14.7±3.5ml/180min, respectively) in rats treated with pilocarpine combined with NOR into the LPBN. Prazosin i.p. also increased 1.8% NaCl intake in rats treated with carbachol i.c.v combined with NOR into the LPBN. The results suggest that different signals inhibit sodium intake in rats treated with cholinergic agonists, among them those produced by increases of arterial pressure that are not efficiently deactivated by NOR acting in the LPBN.
Asunto(s)
Agonistas Colinérgicos/farmacología , Ingestión de Líquidos/fisiología , Norepinefrina/metabolismo , Núcleos Parabraquiales/metabolismo , Cloruro de Sodio Dietético , Animales , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Carbacol/farmacología , Catéteres de Permanencia , Ingestión de Líquidos/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Masculino , Núcleos Parabraquiales/efectos de los fármacos , Pilocarpina/farmacología , Prazosina/farmacología , Ratas Sprague-DawleyRESUMEN
Water and NaCl intake is strongly inhibited by the activation of alpha(2)-adrenergic receptors with clonidine or moxonidine (alpha(2)-adrenergic/imidazoline agonists) injected peripherally or into the forebrain and by serotonin and cholecystokinin in the lateral parabrachial nucleus (LPBN). Considering that alpha(2)-adrenergic receptors exist in the LPBN and the similar origin of serotonergic and adrenergic afferent pathways to the LPBN, in this study we investigated the effects of bilateral injections of moxonidine alone or combined with RX 821002 (alpha(2)-adrenergic antagonist) into the LPBN on 1.8% NaCl and water intake induced by the treatment with s.c. furosemide (10mg/kg)+captopril (5 mg/kg). Additionally, we investigated if moxonidine into the LPBN would modify furosemide+captopril-induced c-fos expression in the forebrain. Male Holtzman rats with cannulas implanted bilaterally in the LPBN were used. Contrary to forebrain injections, bilateral LPBN injections of moxonidine (0.1, 0.5 and 1 nmol/0.2 microl) strongly increased furosemide+captopril-induced 1.8% NaCl intake (16.6+/-2.7, 44.5+/-3.2 and 44.5+/-4.3 ml/2 h, respectively, vs. vehicle: 6.9+/-1.5 ml/2 h). Only the high dose of moxonidine increased water intake (23.3+/-3.8 ml/2 h, vs. vehicle: 12.1+/-2.6 ml/2 h). Prior injections of RX 821002 (10 and 20 nmol/0.2 microl) abolished the effect of moxonidine (0.5 nmol) on 1.8% NaCl intake. Moxonidine into the LPBN did not modify furosemide+captopril-induced c-fos expression in forebrain areas related to the control of fluid-electrolyte balance. The results show that the activation of LPBN alpha(2)-adrenergic receptors enhances furosemide+captopril-induced 1.8% NaCl and water intake. This enhancement was not related to prior alteration in the activity of forebrain areas as suggested by c-fos expression. Previous and present results indicate opposite roles for alpha(2)-adrenergic receptors in the control of sodium and water intake according to their distribution in the rat brain.
Asunto(s)
Apetito/fisiología , Conducta de Ingestión de Líquido/fisiología , Idazoxan/análogos & derivados , Puente/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Cloruro de Sodio Dietético/metabolismo , Antagonistas Adrenérgicos alfa/administración & dosificación , Animales , Antihipertensivos/administración & dosificación , Presión Sanguínea , Captopril/farmacología , Diuréticos/farmacología , Furosemida/farmacología , Genes fos/efectos de los fármacos , Idazoxan/administración & dosificación , Imidazoles/administración & dosificación , Inmunohistoquímica , Masculino , Puente/efectos de los fármacos , Prosencéfalo/efectos de los fármacos , Prosencéfalo/metabolismo , RatasRESUMEN
In this study we investigated: (a) the effects of intracerebroventricular (i.c.v.) injections of moxonidine (an alpha2-adrenergic and imidazoline receptor agonist) on the ingestion of water and NaCl induced by 24 h of water deprivation; (b) the effects of i.c.v. injection of moxonidine on central angiotensin II (ANG II)- and carbachol-induced water intake; (c) the effects of the pre-treatment with i.c.v. idazoxan (an alpha2-adrenergic and imidazoline receptor antagonist) and RX 821002 (a selective alpha2-adrenergic antagonist) on the antidipsogenic action of central moxonidine. Male Holtzman rats had stainless steel cannulas implanted in the lateral cerebral ventricle. Intracerebroventricular injection of moxonidine (5 and 20 nmol/1 microl) reduced the ingestion of 1.5% NaCl solution (4.1 +/- 1.1 and 2.9 +/- 2.5 ml/2 h, respectively vs. control = 7.4 +/- 2.1 ml/2 h) and water intake (2.0 +/- 0.6 and 0.3 +/- 0.2 ml/h, respectively vs. control = 13.0 +/- 1.4 ml/h) induced by water deprivation. Intracerebroventricular moxonidine (5 nmol/1 microl) also reduced i.c.v. ANG II-induced water intake (2.8 +/- 0.9 vs. control = 7.9 +/- 1.7 ml/1 h) and i.c.v. moxonidine (10 and 20 nmol/1 microl) reduced i.c.v. carbachol-induced water intake (4.3 +/- 1.7 and 2.1 +/- 0.9, respectively vs. control = 9.2 +/- 1.0 ml/1 h). The pre-treatment with i.c.v. idazoxan (40 to 320 nmol/1 microl) abolished the inhibitory effect of i.c.v. moxonidine on carbachol-induced water intake. Intracerebroventricular idazoxan (320 nmol/1 microl) partially reduced the inhibitory effect of moxonidine on water deprivation-induced water intake and produced only a tendency to reduce the antidipsogenic effect of moxonidine on ANG II-induced water intake. RX 821002 (80 and 160 nmol/1 microl) completely abolished the antidipsogenic action of moxonidine on ANG II-induced water intake. The results show that central injections of moxonidine strongly inhibit water and NaCl ingestion. They also suggest the involvement of central alpha2-adrenergic receptors in the antidipsogenic action of moxonidine.
Asunto(s)
Antihipertensivos/administración & dosificación , Ingestión de Líquidos/efectos de los fármacos , Imidazoles/administración & dosificación , Cloruro de Sodio Dietético/administración & dosificación , Antagonistas Adrenérgicos alfa/administración & dosificación , Antagonistas Adrenérgicos alfa/farmacología , Angiotensina II/farmacología , Animales , Antihipertensivos/farmacología , Carbacol/administración & dosificación , Carbacol/farmacología , Agonistas Colinérgicos/administración & dosificación , Agonistas Colinérgicos/farmacología , Idazoxan/administración & dosificación , Idazoxan/análogos & derivados , Idazoxan/farmacología , Imidazoles/farmacología , Inyecciones Intraventriculares , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Vasoconstrictores/farmacologíaRESUMEN
OBJECTIVES: To investigate the serum levels of VEGF in patients with rheumatoid arthritis of long duration. METHODS: Serum VEGF levels were measured in 118 patients with long-standing rheumatoid arthritis according to the ACR criteria (mean duration 12 years). The disease activity score was evaluated by the method of van der Heijde et al. RESULTS: Serum levels of VEGF in patients with RA were significantly higher than in healthy controls. VEGF levels showed no correlation with CRP, SAA amyloid protein, or the disease activity score. CONCLUSIONS: Our findings suggest that, contrary to the results reported in patients with early onset RA, where VEGF appears to play an active part in joint inflammation, in long-standing RA elevated VEGF serum levels may be an independent marker although its significance remain to be established.
Asunto(s)
Artritis Reumatoide/sangre , Factores de Crecimiento Endotelial/sangre , Linfocinas/sangre , Adulto , Amiloide/sangre , Artritis Reumatoide/fisiopatología , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The escalating role played by managed care organizations in the health-care system is reflected in the increased demand for cost-effectiveness analyses (CEAs) to assess the balance between economic impact and clinical efficacy. For example, the high incidence and costs associated with colorectal cancer in Latin America calls for a comprehensive economic evaluation to ensure appropriate allocation of limited health-care funds. In addition, the current call for a "societal" perspective of such analyses indicates the need for increased consideration of the concerns of both patient and health-care provider. The introduction of oral tegafur and uracil (UFT) provided the opportunity to evaluate the pharmacoeconomic advantage of the new agent compared with the standard fluorouracil (5-FU). Results of this study indicated an economic advantage for oral UFT vs a 5-FU-based regimen in the treatment of colorectal cancer in Brazil and Argentina. It was further noted that the mild toxicity profile of UFT reduced both the number of clinic visits and the need for venipuncture procedures. Noting that oral UFT may have a positive impact on quality of life in addition to its estimated economic benefit, it was concluded that prospective economic research and quality-of-life evaluations are needed to fully assess the pharmacoeconomic impact of oral UFT.
Asunto(s)
Neoplasias Colorrectales/economía , Tegafur/economía , Uracilo/economía , Argentina , Brasil , Quimioterapia Adyuvante/economía , Neoplasias Colorrectales/tratamiento farmacológico , Costos y Análisis de Costo , Combinación de Medicamentos , Costos de los Medicamentos , Fluorouracilo/administración & dosificación , Fluorouracilo/economía , Humanos , Método de Montecarlo , América del Sur , Tegafur/uso terapéutico , Uracilo/uso terapéuticoRESUMEN
The use of a totally anatomical mitral valve heterograft as a mitral valve substitute has been proven to be technically feasible. A new stentless mitral porcine heart valve substitute was therefore developed to match the physiology and flow characteristics of the left ventricle and mitral valve complex, and tested in non-survival animal experiments. Having sought the approval of the Hospital Ethics Committee and the consent of each individual patient, this valve was implanted into 18 patients with diseased mitral valves. The duration of the procedure is approximately the same as for standard mitral valve replacement. The sizing of the valve and the anchoring of the sutures to the papillary muscle, although very straightforward, do require adherence to a protocol. The immediate clinical results are encouraging, although the first patient required a reoperation because of a patient/valve mismatch. All patients, including the patient reoperated, are in functional class I after four to 26 weeks of follow up. The patients will be followed by monthly clinical and Doppler echocardiographic examinations, as they have been so far, for the next 12 months, and annually thereafter.