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AIM: To evaluate ethiodised oil retention of transarterial embolisation using ethiodised oil (ethiodised oil marking) before computed tomography (CT)-guided percutaneous cryoablation (PCA) according to renal cell carcinoma (RCC) subtype. MATERIALS AND METHODS: Ethiodised oil marking was performed 1-3 days before PCA in 99 patients with 99 RCCs from 2016 to 2020. Ethiodised oil retention on CT images was evaluated retrospectively and CT attenuation values in the tumour were measured. Regions of interest (ROI) were placed on the tumours to calculate: average (ROI-average), maximal (ROI-max), minimum (ROI-min), and standard deviation (ROI-SD). Qualitative scores comprising a five-point scale (5, excellent; 1, poor) were evaluated for the retention scores (RS) of ethiodised oil in the tumour (ethiodised oil-RS) and the visualisation scores (VS) of the boundary between the tumour and renal parenchyma (boundary-VS). RESULTS: The histological subtypes comprised clear cell (ccRCC; n=85), papillary (pRCC; n=6), and chromophobe/oncocytoma renal cell carcinoma (chrRCC; n=8). The mean ROI-average, ROI-max, and ROI-SD were significantly higher in ccRCCs than in chrRCCs and pRCCs (p<0.05). The mean ethiodised oil-RS was significantly lower in pRCCs than in ccRCCs (p=0.039), and the mean boundary-VS was >4 in all subtypes. Even with poor intratumour ethiodised oil retention (n=6), sufficient boundary-VS was obtained due to "inverted marking." All PCA procedures were completed without additional intravenous contrast material injection at the time of PCA. CONCLUSION: Regardless of the tumour subtypes, ethiodised oil marking aids in visualising the boundary between the tumour and parenchyma on non-contrast CT in PCA.
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Carcinoma de Células Renales , Criocirugía , Neoplasias Renales , Humanos , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Aceite Etiodizado , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Diagnóstico DiferencialRESUMEN
This corrects the article DOI: 10.1103/PhysRevLett.104.083401.
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We report on new results of a search for a two-photon interaction with axionlike particles (ALPs). The experiment is carried out at a synchrotron radiation facility using a "light shining through a wall (LSW)" technique. For this purpose, we develop a novel pulsed-magnet system, composed of multiple racetrack magnets and a transportable power supply. It produces fields of about 10 T over 0.8 m with a high repetition rate of 0.2 Hz and yields a new method of probing a vacuum with high intensity fields. The data obtained with a total of 27 676 pulses provide a limit on the ALP-two-photon coupling constant that is more stringent by a factor of 5.2 compared to a previous x-ray LSW limit for the ALP mass â²0.1 eV.
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This study was performed to clarify the influence of liraglutide on gastric emptying in Japanese patients with type 2 diabetes. In 16 patients, the [(13) C]-acetate breath test was performed to compare gastric emptying before and after liraglutide treatment. We found two patterns of response, with gastric emptying being delayed by liraglutide in seven patients (delayers) and not delayed in nine patients (non-delayers). The mean increase of the maximum gastric emptying time was 31 ± 4 min (p < 0.01 vs. baseline) in the delayers, while it was only 2 ± 3 min (p = 0.60 vs. baseline) in the non-delayers. The delayers showed a greater early decrease of AUC-PG from 0 to 60 min, despite no increase of the plasma insulin level compared with non-delayers. In conclusion, the effect of liraglutide treatment on gastric emptying shows heterogeneity, and patients can be classified as delayers or non-delayers.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Vaciamiento Gástrico/efectos de los fármacos , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/administración & dosificación , Adulto , Anciano , Pueblo Asiatico , Glucemia/efectos de los fármacos , Pruebas Respiratorias , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/efectos adversos , Humanos , Hipoglucemiantes/efectos adversos , Liraglutida , Masculino , Persona de Mediana Edad , TaquifilaxisRESUMEN
We report the first direct measurement of the hyperfine transition of the ground state positronium. The hyperfine structure between ortho-positronium and para-positronium is about 203 GHz. We develop a new optical system to accumulate about 10 kW power using a gyrotron, a mode converter, and a Fabry-Pérot cavity. The hyperfine transition has been observed with a significance of 5.4 standard deviations. The transition probability is measured to be A = 3.1(-1.2)(+1.6) × 10(-8) s(-1) for the first time, which is in good agreement with the theoretical value of 3.37 × 10(-8) s(-1).
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In plants, many invading microbial pathogens are recognized by cell-surface pattern recognition receptors, which induce defense responses. Here, we show that the ceramide Phytophthora infestans-ceramide D (Pi-Cer D) from the plant pathogenic oomycete P. infestans triggers defense responses in Arabidopsis. Pi-Cer D is cleaved by an Arabidopsis apoplastic ceramidase, NEUTRAL CERAMIDASE 2 (NCER2), and the resulting 9-methyl-branched sphingoid base is recognized by a plasma membrane lectin receptor-like kinase, RESISTANT TO DFPM-INHIBITION OF ABSCISIC ACID SIGNALING 2 (RDA2). 9-Methyl-branched sphingoid base is specific to microbes and induces plant immune responses by physically interacting with RDA2. Loss of RDA2 or NCER2 function compromised Arabidopsis resistance against an oomycete pathogen. Thus, we elucidated the recognition mechanisms of pathogen-derived lipid molecules in plants.
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Proteínas de Arabidopsis , Arabidopsis , Ceramidas , Interacciones Huésped-Patógeno , Ceramidasa Neutra , Phytophthora infestans , Enfermedades de las Plantas , Arabidopsis/genética , Arabidopsis/inmunología , Arabidopsis/microbiología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ceramidas/metabolismo , Ceramidasa Neutra/genética , Ceramidasa Neutra/metabolismo , Phytophthora infestans/patogenicidad , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores Mitogénicos/genética , Receptores Mitogénicos/metabolismoRESUMEN
CP violation in the quark sector has been well established over the last decade, but has not been observed in the lepton sector. We search for CP violating decay processes in positronium, using the angular correlation of (S x k{1})(S x k{1}x k{2}), where S is the positronium spin and k{1}, k{2} are the directions of the positronium decay photons. To a sensitivity of 2.2x10{-3}, no CP violation has been found, which is at the level of the CP violation amplitude in the K meson. A 90% confidence interval of the CP violation parameter (C{CP}) was determined to be -0.0023
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We present magnetic susceptibility, heat capacity, and neutron diffraction measurements of polycrystalline Nd2Ru2O7 down to 0.4 K. Three anomalies in the magnetic susceptibility measurements at 146, 21 and 1.8 K are associated with an antiferromagnetic ordering of the Ru4+ moments, a weak ferromagnetic signal attributed to a canting of the Ru4+ and Nd3+ moments, and a long-range-ordering of the Nd3+ moments, respectively. The long-range order of the Nd3+ moments was observed in all the measurements, indicating that the ground state of the compound is not a spin glass. The magnetic entropy of Rln2 accumulated up to 5 K, suggests the Nd3+ has a doublet ground state. Lattice distortions accompany the transitions, as revealed by neutron diffraction measurements, and in agreement with earlier synchrotron x-ray studies. The magnetic moment of the Nd3+ ion at 0.4 K is estimated to be 1.54(2)µ B and the magnetic structure is all-in all-out as determined by our neutron diffraction measurements.
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Insulin has pleiotropic effects on the regulation of cell physiology through binding to its receptor. The wide variety of tyrosine phosphorylation motifs of insulin receptor substrate 1 (IRS-1), a substrate for the activated insulin receptor tyrosine kinase, may account for the multiple functions of insulin. Recent studies have shown that activation of the insulin receptor leads to the regulation of focal adhesion proteins, such as a dephosphorylation of focal adhesion kinase (pp125FAK). We show here that C-terminal Src kinase (Csk), which phosphorylates C-terminal tyrosine residues of Src family protein tyrosine kinases and suppresses their kinase activities, is involved in this insulin-stimulated dephosphorylation of focal adhesion proteins. We demonstrated that the overexpression of Csk enhanced and prolonged the insulin-induced dephosphorylation of pp125FAK. Another focal adhesion protein, paxillin, was also dephosphorylated upon insulin stimulation, and a kinase-negative mutant of Csk was able to inhibit the insulin-induced dephosphorylation of pp125FAK and paxillin. Although we have shown that the Csk Src homology 2 domain can bind to several tyrosine-phosphorylated proteins, including pp125FAK and paxillin, a majority of protein which bound to Csk was IRS-1 when cells were stimulated by insulin. Our data also indicated that tyrosine phosphorylation levels of IRS-1 appear to be paralleled by the dephosphorylation of the focal adhesion proteins. We therefore propose that the kinase activity of Csk, through the insulin-induced complex formation of Csk with IRS-1, is involved in insulin's regulation of the phosphorylation levels of the focal adhesion proteins, possibly through inactivation of the kinase activity of c-Src family kinases.
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Moléculas de Adhesión Celular/metabolismo , Proteínas del Citoesqueleto/metabolismo , Insulina/farmacología , Fosfoproteínas/metabolismo , Procesamiento Proteico-Postraduccional , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas/fisiología , Receptor de Insulina/fisiología , Secuencia de Aminoácidos , Animales , Células CHO , Proteína Tirosina Quinasa CSK , Bovinos , Cricetinae , Cricetulus , Quinasa 1 de Adhesión Focal , Proteína-Tirosina Quinasas de Adhesión Focal , Proteínas Sustrato del Receptor de Insulina , Sustancias Macromoleculares , Datos de Secuencia Molecular , Paxillin , Fosfoproteínas Fosfatasas/metabolismo , Fosforilación , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteínas Tirosina Quinasas/genética , Receptor de Insulina/efectos de los fármacos , Proteínas Recombinantes de Fusión/metabolismo , Transducción de Señal , Transfección , Familia-src Quinasas/metabolismoRESUMEN
OBJECTIVES: The study evaluated the relationship between plasma cardiotrophin-1 (CT-1) concentration and left ventricular (LV) mass in dilated cardiomyopathy (DCM) patients with congestive heart failure (CHF). BACKGROUND: Cardiotrophin-1 is a newly identified member of the interleukin-6 (IL-6) family of cytokines and one of the endogenous ligands for gp130 signaling pathways in the heart, and it has potent hypertrophic and survival effects on cardiac myocytes. However, the clinical significance of CT-1 is poorly understood. METHODS: We measured the plasma CT-1 level in 51 consecutive patients with DCM. Patients were classified into two groups: small LV mass index group and large LV mass index group, based on the median level of LV mass index. RESULTS: The plasma CT-1 level was increased in DCM patients with the severity of CHF and was significantly higher in the large LV mass group than in the small LV mass group, despite the absence of a difference in LV ejection fraction between the two groups. In addition, there was a significant positive correlation between the plasma CT-1 level and the LV mass index (r = 0.627, p < 0.0001). According to stepwise multivariate analyses among hemodynamic and neurohumoral factors, a high plasma CT-1 level showed an independent and significant positive relationship with a large LV mass index in patients with DCM. CONCLUSIONS: These results indicate that the plasma CT-1 level is increased in patients with DCM and is significantly correlated with the LV mass index, suggesting that CT-1 plays an important role in structural LV remodeling in patients with DCM.
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Cardiomiopatía Dilatada/sangre , Cardiomiopatía Dilatada/complicaciones , Citocinas/sangre , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/patología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/patología , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Angiotensina II/sangre , Cardiomiopatía Dilatada/inmunología , Estudios de Casos y Controles , Citocinas/fisiología , Femenino , Insuficiencia Cardíaca/clasificación , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Humanos , Hipertrofia Ventricular Izquierda/clasificación , Hipertrofia Ventricular Izquierda/fisiopatología , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Norepinefrina/sangre , Valor Predictivo de las Pruebas , Radioinmunoensayo , Transducción de Señal/inmunología , Volumen Sistólico , Remodelación Ventricular/inmunologíaRESUMEN
Thymidylate synthase (TS) is thought to be one of the target genes that the E2F1 transcription factor binds to and regulates. However, the relationship between the expressions of TS and E2F1 in primary colon cancer specimens remains unclear. The aim of this study was to define the relation of TS and E2F1 gene expressions in tumor samples from 23 colon cancer patients. TS and E2F1 gene expressions were measured by TaqMan reverse transcription-PCR assay using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard and expressed as a TS:GAPDH or E2F1:GAPDH mRNA ratio. A close relationship was found between TS gene expression and E2F1 gene expression (r2 = 0.598, P < 0.001) in 23 tumor samples analyzed. Surprisingly, a high correlation between TS gene expression and E2F1 gene expression was observed even in advanced tumors from stage IV colon cancer patients. These results suggest that transcription of the TS gene may be regulated by E2F1 in primary colon cancer specimens and that this gene-regulatory pathway from E2F1 to TS may be highly conserved during malignant progression. Four of the 23 patients showed TS overexpression with increased E2F1 expression. These results suggest that the ability of a tumor to increase TS expression may possibly be due to an overexpression of E2F1. Although the number of patients was relatively small, our study provides new insights into the molecular mechanisms underlying the regulation of TS expression in colon cancers.
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Proteínas Portadoras , Proteínas de Ciclo Celular , Neoplasias del Colon/genética , Proteínas de Unión al ADN , Regulación Neoplásica de la Expresión Génica , Timidilato Sintasa/genética , Factores de Transcripción/genética , Adulto , Anciano , Anciano de 80 o más Años , Calibración , Neoplasias del Colon/enzimología , Neoplasias del Colon/patología , Factores de Transcripción E2F , Factor de Transcripción E2F1 , Femenino , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa/métodos , ARN Neoplásico/genética , Análisis de Regresión , Proteína 1 de Unión a Retinoblastoma , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción DP1RESUMEN
We investigated the efficacy and toxicity of salvage chemotherapy with weekly docetaxel for recurrent ovarian cancer, tubal cancer, and primary peritoneal cancer after treatment with regimens containing platinum or paclitaxel. The 15 subjects were managed as outpatients and received at least two courses of docetaxel therapy (35 mg/m2 on days 1, 8 and 15). Antitumour activity was assessed radiologically and from the CA-125 level. Among five patients with measurable lesions, one showed partial remission and three showed stable disease. Based on CA-125 levels, there were three partial remissions and five patients with stable disease (progression-free survival was 7.5 months and 7.6 months, respectively). During 61 courses, the severe toxicities were grade 3 leukopaenia/neutropaenia (6.7%) or grade 2 oedema and pleural effusion (13.3%). Weekly docetaxel may be useful salvage chemotherapy for recurrent ovarian cancer, tubal cancer, and peritoneal cancer, especially as tumour dormancy therapy.
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Antineoplásicos/administración & dosificación , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Taxoides/administración & dosificación , Adulto , Anciano , Biomarcadores de Tumor/sangre , Antígeno Ca-125/sangre , Docetaxel , Esquema de Medicación , Neoplasias de las Trompas Uterinas/sangre , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Neoplasias Ováricas/sangre , Paclitaxel/uso terapéutico , Neoplasias Peritoneales/sangre , Proyectos Piloto , Compuestos de Platino/uso terapéutico , Resultado del TratamientoRESUMEN
Accumulating evidence on the molecular and cellular basis of ischemia/reperfusion-induced neurodegeneration suggests that oxidative stress is involved. Heme oxygenase (HO) and cyclooxygenase (COX) play physiologically important roles in the CNS. Conversely, HO and COX also can increase oxidative stress. Recent studies suggest that c-Jun phosphorylation is an important step in some forms of stress-induced neuronal apoptosis. In this study, the authors tried to clarify the association of HO and COX with c-Jun phosphorylation. Inducible forms of HO and COX (HO-1 and COX-2, respectively) were transiently induced in CA1 pyramidal neurons after ischemia. c-Jun also was induced in pyramidal neurons throughout the hippocampal formation, but its phosphorylation was limited to CA1. In contrast, these molecules were constitutively expressed at low levels. Most (84%) of the CA1 pyramidal neurons examined expressed HO-1, COX-2, or both, and such expression showed good co-localization with c-Jun phosphorylation. These results suggest the following: (1) c-Jun phosphorylation was associated with ischemia/reperfusion-induced neuronal apoptosis; (2) HO-1 and COX-2 were induced in CA1 pyramidal neurons, which undergo cell death; and (3) most CA1 pyramidal neurons expressed HO-1, COX-2, or both, which strongly suggests that these are candidates for neuron killers.
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Hemo Oxigenasa (Desciclizante)/metabolismo , Ataque Isquémico Transitorio/metabolismo , Isoenzimas/metabolismo , Prosencéfalo/irrigación sanguínea , Prostaglandina-Endoperóxido Sintasas/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Animales , Muerte Celular , Ciclooxigenasa 2 , Hemo-Oxigenasa 1 , Inmunohistoquímica , Ataque Isquémico Transitorio/patología , Masculino , Fosforilación , Células Piramidales/metabolismo , Células Piramidales/patología , Ratas , Ratas WistarRESUMEN
UNLABELLED: To develop a camera-based method for evaluating renal function with 99mTc-mercaptoacetyltriglycine (MAG3), we examined the relationship between various renogram parameters and 99mTc-MAG3 clearance. METHODS: Twenty-one patients underwent renal scintigraphy with 99mTc-MAG3. Eighty 3-s frames were obtained after the bolus injection of 250 MBq tracer, followed by the collection of 52 30-s frames. Regions of interest were drawn for the kidneys, perirenal background areas and subrenal background areas, and background-subtracted renograms were generated. Renal accumulation at 0.5-1.5, 0.5-2, 1-2, 1-2.5 and 1.5-2.5 min after tracer arrival in the kidney was calculated as area under the background-subtracted renogram, and percent renal uptake was obtained after correction for soft-tissue attenuation and injected dose. The slope of the renogram was determined for the same segments used in calculating area under the renogram, and slope index was computed as slope corrected for attenuation and injected dose. Percent renal uptakes and slope indices were correlated by linear regression analysis with 99mTc-MAG3 clearance measured using a single blood sampling method. RESULTS: Among the values of percent renal uptake, the value obtained at 1.5-2.5 min using the perirenal background correlated best with 99mTc-MAG3 clearance. The slope index at 0.5-1.5 or 0.5-2 min using the subrenal background provided better accuracy than percent renal uptake for predicting clearance. There were no substantial differences in the relative function of the right kidney between the methods using percent renal uptake and slope index. CONCLUSION: 99mTc-MAG3 clearance can be assessed with acceptable accuracy by a camera-based method. The method based on the slope of the renogram may replace the one based on the area under the renogram in evaluating renal function from 99mTc-MAG3 renograms.
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Renografía por Radioisótopo/métodos , Tecnecio Tc 99m Mertiatida , Recolección de Muestras de Sangre , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Radiofármacos , Factores de TiempoRESUMEN
1. The abilities of muscarinic agonists (arecoline, bethanechol, carbachol, McN-A343, methacholine, pilocarpine) to inhibit isoprenaline-induced cyclic AMP production in chopped fragments (via M(2) receptors), and to evoke cationic current (I(cat)) (via M(2) receptors) or calcium store release (via M3 receptors) in enzyme-dispersed, single voltage-clamped cells from longitudinal smooth muscle of the guinea-pig small intestine were examined. 2. All muscarinic agonists (1 - 300 microM) examined inhibited isoprenaline (1 microM)-induced accumulation of cyclic AMP, the IC(50) varying from 52 to 248 microM. However, their relative potencies to evoke this M(2) effect were not significantly correlated with their ability to evoke I(cat), also a M(2) effect, whether or not calcium stores were depleted; pilocarpine and McN-A343 inhibited the I(cat) response to carbachol. 3. Muscarinic agonists (concentration 300 or 1000 microM), except pilocarpine and McN-A343 which were ineffective, evoked Ca(2+)-activated K(+) current (I(K-Ca)) resulting from Ca(2+) store release (M(3) effect). Their effectiveness was tested by estimating residual stored calcium by subsequent application of caffeine (10 mM). The relative potencies to evoke Ca(2+) store release (M(3)) and for I(cat) activation (M(2)) were closely correlated (P<0.001). 4. These data might be explained if M(2)-mediated adenylyl cyclase inhibition and I(cat) activation involve different G proteins, or involve different populations of M(2) receptors. The observed correlation of agonist potency between I(cat) activation and Ca(2+) store release supports the proposal (Zholos & Bolton, 1997) that M(3) activation can potentiate M(2)-cationic channel coupling through Ca(2+)-independent mechanisms.
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Intestino Delgado/citología , Agonistas Muscarínicos/farmacología , Músculo Liso/efectos de los fármacos , Receptores Muscarínicos/metabolismo , Animales , Calcio/metabolismo , AMP Cíclico/metabolismo , Electrofisiología , Cobayas , Intestino Delgado/fisiología , Masculino , Músculo Liso/metabolismo , Músculo Liso/fisiología , Canales de Potasio Calcio-Activados/fisiología , Receptor Muscarínico M2 , Receptor Muscarínico M3RESUMEN
The high- and low-avoidance animal (HAA and LAA respectively) strains of Hatano rats were originally selected and bred from Sprague-Dawley rats for their performance in the shuttle-box task. The present study focused on the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis of HAA and LAA rats in response to restraint stress. The restraint stress induced an elevation in plasma concentrations of ACTH, prolactin, corticosterone and progesterone. Peak levels of plasma ACTH during stress conditions were significantly higher in HAA rats than in LAA rats, while peak levels of prolactin were significantly lower in HAA rats than in LAA rats. Under stress conditions, ACTH and prolactin synthesis in the anterior pituitary glands was significantly higher in HAA rats compared with LAA rats. The peak plasma concentrations of corticosterone, during restraint stress, were significantly higher in LAA rats compared with HAA rats. These results indicate that the response of the hypothalamo-pituitary axis to acute restraint stress is greater in HAA rats than in LAA rats, whereas the ACTH-induced adrenal response of corticosterone release is higher in LAA rats than in HAA rats. On the other hand, prolactin secretory activity is higher in LAA rats compared with HAA rats. These differences in endocrine responses to stress may be involved in the regulation of the avoidance responses in the shuttle-box task.
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Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Estrés Psicológico/metabolismo , Hormona Adrenocorticotrópica/sangre , Animales , Cruzamiento , Corticosterona/sangre , Masculino , Progesterona/sangre , Prolactina/sangre , Ratas , Ratas Sprague-DawleyRESUMEN
Hatano high-avoidance (HAA) and low-avoidance (LAA) animals were originally selected from Sprague-Dawley rats for good and poor active avoidance learning in a shuttle box. We studied the endocrinological profile in lactating rats to determine the effect of suckling during mid-lactation in HAA and LAA rats. The pups were separated from their mother rats 6 h before the onset of suckling and blood samples were drawn from unanaesthetized mother rats via a jugular cannula at 0, 5 and 15 min after the suckling stimulus and then 15, 45 and 105 min after pups were removed. Plasma concentrations of oxytocin in HAA rats were significantly higher than in LAA rats during the suckling period. Plasma concentrations of prolactin and ACTH in HAA rats were significantly higher than in LAA rats during the suckling period, and at 15 min and 45 min after the pups were removed. However, there were no strain differences in circulating corticosterone between the two lines, indicating that the response of the hypothalamo-pituitary axis to the suckling stimulus was greater in HAA rats than in LAA rats, whereas the ACTH-induced adrenal response of corticosterone release was higher in LAA rats than in HAA rats. Since dopamine from the median eminence inhibits prolactin secretion from the lactotrophs of the anterior pituitary, and tuberoinfundibular dopaminergic neurones are partially regulated by the level of circulating prolactin, we evaluated the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis. TH, measured by the accumulation of 3,4-dihydroxyphenylalanine, was significantly higher in HAA rats than in LAA rats before the suckling stimulus. After the suckling stimulus, TH activity in HAA rats was significantly lower than before suckling, whereas TH activity in LAA rats was not changed. These findings clearly demonstrated that apparent differences between the two Hatano lines exist in endocrinological profiles during suckling. These strain differences probably originate from neurotransmitter changes, such as dopamine.
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Hormona Adrenocorticotrópica/sangre , Reacción de Prevención , Lactancia/metabolismo , Oxitocina/sangre , Prolactina/sangre , Animales , Animales Lactantes , Dopamina/biosíntesis , Femenino , Ratas , Ratas Endogámicas , Ratas Sprague-Dawley , Tirosina 3-Monooxigenasa/análisis , Tirosina 3-Monooxigenasa/metabolismo , Aumento de PesoRESUMEN
BACKGROUND: We previously demonstrated the circadian variation of water-immersion restraint stress (WRS)-induced gastric mucosal lesions in rats. AIM: To investigate the roles of melatonin and prostaglandin in the gastric mucosa in circadian modulation of WRS. METHODS: Fasted rats were subjected to 4-h WRS during both the diurnal and nocturnal phases of a light/dark cycle. Mucosal lesions, serum melatonin concentrations, mucosal generation of prostaglandin E2 (PGE2) and mucosal gene expressions of cyclooxygenase (COX)-1 and -2 were evaluated. RESULTS: Lesion area after 4-h stress during the dark phase was significantly smaller than that in light-phase controls. Serum melatonin concentration in control rats during the light phase was significantly increased 4 h after WRS, but PGE2 generation was decreased by 48% as compared to that in intact mucosa before stress. In the dark phase, melatonin concentration after 4-h WRS was significantly depressed as compared with the control level at the corresponding time. PGE2 concentrations after 4-h WRS in the dark phase were not decreased compared with the control level at the corresponding time, although PGE2 level was significantly lower than that in light-phase controls. Expression of COX-1 and COX-2 mRNA was detected after exposure to stress in both the light and dark phases. CONCLUSION: These results suggest that circadian rhythm has an important role in the formation of stress-induced gastric mucosal lesions in rats. The circadian rhythm of melatonin responses and PGE2 generation may contribute to nocturnal/diurnal rhythmicity of gastric mucosal defences between day and night.
Asunto(s)
Ritmo Circadiano , Dinoprostona/biosíntesis , Mucosa Gástrica/metabolismo , Melatonina/sangre , Úlcera Gástrica/metabolismo , Animales , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Mucosa Gástrica/patología , Isoenzimas/genética , Masculino , Proteínas de la Membrana , Prostaglandina-Endoperóxido Sintasas/genética , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Úlcera Gástrica/etiología , Úlcera Gástrica/fisiopatología , Estrés Fisiológico/complicacionesRESUMEN
BACKGROUND: Leukotriene (LT) and thromboxane A2 (TXA2) receptor antagonists have been used in the treatment of asthma. OBJECTIVES: We examined the effects of an LT receptor antagonist, TXA2 receptor antagonist, and TXA2 synthetase inhibitor on bronchoprovocation test (BPT) in patients with mild-to-moderate atopic asthma. METHODS: BPT was performed four times in each of six asthmatics. Development of the immediate asthmatic reaction (IAR) and late asthmatic reaction (LAR) was confirmed on the first BPT (BPT1). After a 7-day washout period, an LT receptor antagonist (pranlukast, 450 mg/d), TXA2 receptor antagonist (seratrodast, 80 mg/d), or TXA2 synthetase inhibitor (ozagrel, 800 mg/d) was administered orally over 7 days at random using a cross-over method (BPT2-4). Blood levels of LTB4, LTC4, LTD4, 11-dehydrothromboxane B2, eosinophil cationic protein, and histamine were measured at reaction phases of pre-BPT, IAR, and LAR. RESULTS: Administration of pranlukast suppressed IAR by 80.5% (p < 0.0001) and LAR by 54.6% (p = 0.0391). Ozagrel significantly suppressed IAR by 39.5% (p = 0.0413), but the fall in FEV1 was >20% (21.56+/-4.173%). Seratrodast did not suppress IAR or LAR. Blood levels of chemical mediators did not correlate with the suppressive effects of the tested drugs. CONCLUSIONS: The LT receptor antagonist was considered to be the most effective. LT might play a more important role in the pathogenesis of asthma than TXA2. Our data showed that measurement of blood levels of chemical mediators is not useful in identifying the pathogenic mechanisms of asthma.
Asunto(s)
Asma/tratamiento farmacológico , Benzoquinonas/uso terapéutico , Broncoconstricción/efectos de los fármacos , Cromonas/uso terapéutico , Ácidos Heptanoicos/uso terapéutico , Antagonistas de Leucotrieno , Proteínas de la Membrana , Metacrilatos/uso terapéutico , Receptores de Tromboxanos/antagonistas & inhibidores , Ribonucleasas , Tromboxano-A Sintasa/antagonistas & inhibidores , Administración Oral , Adulto , Antiasmáticos/administración & dosificación , Antiasmáticos/uso terapéutico , Antígenos/efectos adversos , Asma/sangre , Asma/diagnóstico , Asma/etiología , Proteínas Sanguíneas/metabolismo , Pruebas de Provocación Bronquial , Estudios Cruzados , Proteínas en los Gránulos del Eosinófilo , Femenino , Estudios de Seguimiento , Histamina/sangre , Humanos , Masculino , Receptores de Leucotrienos/sangre , Receptores de Tromboxanos/sangre , Tromboxano B2/análogos & derivados , Tromboxano B2/sangre , Tromboxano-A Sintasa/sangre , Resultado del TratamientoRESUMEN
The cellular fatty acid compositions of 26 strains of methicillin-resistant Staphylococcus aureus (MRSA) and 17 strains of methicillin-susceptible S. aureus (MSSA) were analyzed by gas-liquid chromatography. The fatty acid compositions of the two groups were very similar with 16 identified components. The major fatty acids were Ci14 = 0, Ci15 = 0, C18 = 0 and C20 = 0. Among these fatty acids, the percentage of the Ci15 = 0 fatty acid component of MRSA strains (11.4 +/- 3.9%) was statistically higher than that of MSSA strains (6.2 +/- 2.4%) (p < 0.001). On the other hand, the percentage of the C20 = 0 fatty acid components of MRSA strains (20.2 +/- 8.8%) was statistically lower than that of MSSA strains (30.7 +/- 10.4%) (p < 0.001). The production of beta-lactamase and beta-hemolysin in both groups' strain was also unrelated to the relative amounts of the fatty acid components. These results indicated a statistical tendency for the percentage fatty acid compositions of the MRSA strains to be quantitatively different from those of the MSSA for both the Ci15 = 0 and C20 = 0 fatty acid components. Analysis of the fatty acid compositions may have an application in the differentiation of MRSA and MSSA strains.