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6-Nitrodopamine is a novel catecholamine released by vascular tissues, heart, and vas deferens. The aim of this study was to investigate whether 6-nitrodopamine is released from the thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) and to evaluate the relaxing and anti-contractile actions of this catecholamine. Release of 6-nitrodopamine, dopamine, noradrenaline, and adrenaline was assessed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The relaxations induced by 6-nitrodopamine and by the selective dopamine D2 receptor antagonist L-741,626 were evaluated on U-46619 (3 nM)-pre-contracted vessels. The effects of 6-nitrodopamine and L-741,626 on the contractions induced by electric-field stimulation (EFS), dopamine, noradrenaline, and adrenaline were also investigated. Both aorta and pulmonary artery rings exhibited endothelium-dependent release of 6-nitrodopamine, which was significantly reduced by the NO synthesis inhibitor L-NAME. Addition of 6-nitrodopamine or L-741,626 caused concentration-dependent relaxations of both vascular tissues, which were almost abolished by endothelium removal, whereas L-NAME and the soluble guanylate cyclase inhibitor ODQ had no effect on 6-nitrodopamine-induced relaxations. Additionally, pre-incubation with 6-nitrodopamine antagonized the dopamine-induced contractions, without affecting the noradrenaline- and adrenaline-induced contractions. Pre-incubation with L-741,626 antagonized the contractions induced by all catecholamines. The EFS-induced contractions were significantly increased by L-NAME, but unaffected by ODQ. Immunohistochemical assays showed no immunostaining of the neural tissue markers S-100 and calretinin in either vascular tissue. The results indicated that 6-nitrodopamine is the major catecholamine released by marmoset vascular tissues, and it acts as a potent and selective antagonist of dopamine D2-like receptors. 6-nitrodopamine release may be the major mechanism by which NO causes vasodilatation.
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Callithrix , Dopamina , Animales , Masculino , Dopamina/farmacología , Aorta Torácica/fisiología , NG-Nitroarginina Metil Éster/farmacología , Arteria Pulmonar , Cromatografía Liquida , Espectrometría de Masas en Tándem , Endotelio , Norepinefrina/farmacología , Catecolaminas/farmacología , Epinefrina , Endotelio Vascular , Óxido Nítrico/fisiologíaRESUMEN
6-Nitrodopamine is a novel catecholamine released by vascular tissues, heart, and vas deferens. The aim of this study was to investigate whether 6-nitrodopamine is released from the thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) and to evaluate the relaxing and anti-contractile actions of this catecholamine. Release of 6-nitrodopamine, dopamine, noradrenaline, and adrenaline was assessed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The relaxations induced by 6-nitrodopamine and by the selective dopamine D2 receptor antagonist L-741,626 were evaluated on U-46619 (3 nM)-pre-contracted vessels. The effects of 6-nitrodopamine and L-741,626 on the contractions induced by electric-field stimulation (EFS), dopamine, noradrenaline, and adrenaline were also investigated. Both aorta and pulmonary artery rings exhibited endothelium-dependent release of 6-nitrodopamine, which was significantly reduced by the NO synthesis inhibitor L-NAME. Addition of 6-nitrodopamine or L-741,626 caused concentration-dependent relaxations of both vascular tissues, which were almost abolished by endothelium removal, whereas L-NAME and the soluble guanylate cyclase inhibitor ODQ had no effect on 6-nitrodopamine-induced relaxations. Additionally, pre-incubation with 6-nitrodopamine antagonized the dopamine-induced contractions, without affecting the noradrenaline- and adrenaline-induced contractions. Pre-incubation with L-741,626 antagonized the contractions induced by all catecholamines. The EFS-induced contractions were significantly increased by L-NAME, but unaffected by ODQ. Immunohistochemical assays showed no immunostaining of the neural tissue markers S-100 and calretinin in either vascular tissue. The results indicated that 6-nitrodopamine is the major catecholamine released by marmoset vascular tissues, and it acts as a potent and selective antagonist of dopamine D2-like receptors. 6-nitrodopamine release may be the major mechanism by which NO causes vasodilatation.
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In light of forensic evidence indicating duplication and/or manipulation of western blot images the Editor-in-Chief is retracting the article cited above.
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Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age.
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Humanos , Masculino , Femenino , Lactante , Atresia Biliar/diagnóstico , Enfermedades de Inicio Tardío/diagnóstico , Hígado/patología , Atresia Biliar/patología , Atresia Biliar/cirugía , Biopsia , Diagnóstico Diferencial , Arteria Hepática/patología , Enfermedades de Inicio Tardío/patología , Enfermedades de Inicio Tardío/cirugíaRESUMEN
Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age.
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Atresia Biliar/diagnóstico , Enfermedades de Inicio Tardío/diagnóstico , Hígado/patología , Atresia Biliar/patología , Atresia Biliar/cirugía , Biopsia , Diagnóstico Diferencial , Femenino , Arteria Hepática/patología , Humanos , Lactante , Enfermedades de Inicio Tardío/patología , Enfermedades de Inicio Tardío/cirugía , MasculinoRESUMEN
PURPOSE: Ultrasound (US) therapy is an electrothermotherapeutic modality that uses US energy to provoke physical and chemical alterations. US therapy has been widely used in physical therapy. However, in clinical practice, it is contraindicated in cancer patients due to the possibility of exacerbating tumor growth. METHODS: Sixty-eight female Sprague-Dawley rats bred in UNIFAE vivarium were studied. At 50 days of age, 7,12-dimetylbenz(a)anthracene (7,12-DMBA) was administered to 35 rats by gastric gavage to induce mammary cancer. After 90 days the mammary glands of the rats belonging to the group with mammary cancer induction and stimulated by US were removed. Animals received either continuous or pulsed US. US waves were generated at a frequency of 1 MHz during 10 days, with an intensity dose of 0.5 W in the continuous group, and 0.9 W (duty cycle: 20%) in the pulsed group. RESULTS: Among the rats treated with continuous US, 44.4% developed local recurrence, while among the rats treated with pulsed US, 22.2% had local tumor recurrence (p<0.05). No evidence of distant metastases was shown in any of the rats studied. CONCLUSION: The use of continuous and pulsed therapeutic US promoted the development of local recurrence of mammary cancer in female Sprague-Dawley rats in the postoperative period.
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Neoplasias Mamarias Experimentales/terapia , Recurrencia Local de Neoplasia/terapia , Terapia por Ultrasonido/métodos , Animales , Femenino , Ratas , Ratas Sprague-DawleyRESUMEN
AIMS/HYPOTHESIS: A high-fat dietary intake induces obesity and subclinical inflammation, which play important roles in insulin resistance. Recent studies have suggested that increased concentrations of circulating lipopolysaccharide (LPS), promoted by changes in intestinal permeability, may have a pivotal role in insulin resistance. Thus, we investigated the effect of gut microbiota modulation on insulin resistance and macrophage infiltration. METHODS: Swiss mice were submitted to a high-fat diet with antibiotics or pair-feeding for 8 weeks. Metagenome analyses were performed on DNA samples from mouse faeces. Blood was collected to determine levels of glucose, insulin, LPS, cytokines and acetate. Liver, muscle and adipose tissue proteins were analysed by western blotting. In addition, liver and adipose tissue were analysed, blinded, using histology and immunohistochemistry. RESULTS: Antibiotic treatment greatly modified the gut microbiota, reducing levels of Bacteroidetes and Firmicutes, overall bacterial count and circulating LPS levels. This modulation reduced levels of fasting glucose, insulin, TNF-α and IL-6; reduced activation of toll-like receptor 4 (TLR4), c-Jun N-terminal kinase (JNK), inhibitor of κ light polypeptide gene enhancer in B cells, kinase ß (IKKß) and phosphorylated IRS-1 Ser307; and consequently improved glucose tolerance and insulin tolerance and action in metabolically active tissues. In addition, there was an increase in portal levels of circulating acetate, which probably contributed to an increase in 5'-AMP-activated protein kinase (AMPK) phosphorylation in mice. We observed a striking reduction in crown-like structures (CLS) and F4/80(+) macrophage cells in the adipose tissue of antibiotic-treated mice. CONCLUSIONS/INTERPRETATION: These results suggest that modulation of gut microbiota in obesity can improve insulin signalling and glucose tolerance by reducing circulating LPS levels and inflammatory signalling. Modulation also appears to increase levels of circulating acetate, which activates AMPK and finally leads to reduced macrophage infiltration.
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Antibacterianos/farmacología , Dieta Alta en Grasa/efectos adversos , Tracto Gastrointestinal/microbiología , Insulina/fisiología , Metagenoma/efectos de los fármacos , Obesidad/fisiopatología , Transducción de Señal/fisiología , Quinasas de la Proteína-Quinasa Activada por el AMP , Acetatos/sangre , Animales , Bacteroides/aislamiento & purificación , Movimiento Celular/fisiología , Citocinas/sangre , Modelos Animales de Enfermedad , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/patología , Resistencia a la Insulina/fisiología , Lipopolisacáridos/sangre , Macrófagos/patología , Masculino , Ratones , Obesidad/etiología , Obesidad/patología , Proteínas Quinasas/fisiologíaRESUMEN
PURPOSE: Glutathione S-transferase (GST) is a cytosolic enzymatic system involved in cellular detoxifying process. In vitro studies have shown that the presence of this enzymatic system in breast carcinoma cells can accelerate the elimination of drugs commonly used in chemotherapy, thereby decreasing its efficacy. The aim of the present study was to evaluate the association between GST Pi expression by breast carcinoma cells and disease-free and overall survival. METHODS: Ninety-five female patients with invasive breast carcinoma submitted to surgical treatment and adjuvant chemotherapy from January, 1995 to June, 1997 and followed until August, 2006 were evaluated. The expression of GST Pi in breast carcinoma cells, determined by immunohistochemistry, was correlated with several clinical and pathological parameters of prognostic significance. RESULTS: There were 36 (37.9%) GST Pi-positive cases. GST Pi immunoexpression was not significantly correlated with patient's age, histological tumor type, clinical stage, hormone receptor status and survival. On the other hand, GST Pi positivity showed a significant correlation with a lower histological grade/C-erb-B2 negative breast carcinoma phenotype. CONCLUSION: The findings suggest that GST Pi expression does not constitute a satisfactory prognostic factor in breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/enzimología , Carcinoma Ductal de Mama/enzimología , Carcinoma Lobular/enzimología , Gutatión-S-Transferasa pi/metabolismo , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/mortalidad , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/mortalidad , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Tasa de SupervivenciaRESUMEN
BACKGROUND AND PURPOSE: Diabetic cystopathy is one of the most common and incapacitating complications of diabetes mellitus. This study aimed to evaluate the functional, structural and molecular alterations of detrusor smooth muscle (DSM) in streptozotocin-induced diabetic mice, focusing on the contribution of Ca(2+) influx through L-type voltage-operated Ca(2+) channels (L-VOCC). EXPERIMENTAL APPROACH: Male C57BL/6 mice were injected with streptozotocin (125 mg·kg(-1) ). Four weeks later, contractile responses to carbachol, α,ß-methylene ATP, KCl, extracellular Ca(2+) and electrical-field stimulation were measured in urothelium-intact DSM strips. Cystometry and histomorphometry were performed, and mRNA expression for muscarinic M(2) /M(3) receptors, purine P2X1 receptors and L-VOCC in the bladder was determined. KEY RESULTS: Diabetic mice exhibited higher bladder capacity, frequency, non-void contractions and post-void pressure. Increased bladder weight, wall thickness, bladder volume and neural tissue were observed in diabetic bladders. Carbachol, α,ß-methylene ATP, KCl, extracellular Ca(2+) and electrical-field stimulation all produced greater DSM contractions in diabetic mice. The L-VOCC blocker nifedipine almost completely reversed the enhanced DSM contractions in bladders from diabetic animals. The Rho-kinase inhibitor Y27632 had no effect on the enhanced carbachol contractions in the diabetic group. Expression of mRNA for muscarinic M(3) receptors and L-VOCC were greater in the bladders of diabetic mice, whereas levels of M(2) and P2X1 receptors remained unchanged. CONCLUSIONS AND IMPLICATIONS: Diabetic mice exhibit features of urinary bladder dysfunction, as characterized by overactive DSM and decreased voiding efficiency. Functional and molecular data suggest that overactive DSM in diabetes is the result of enhanced extracellular Ca(2+) influx through L-VOCC.
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Canales de Calcio Tipo L/metabolismo , Diabetes Mellitus Experimental/complicaciones , Enfermedades de la Vejiga Urinaria/etiología , Amidas/farmacología , Animales , Bloqueadores de los Canales de Calcio/farmacología , Cloruro de Calcio/farmacología , Carbacol/farmacología , Agonistas Colinérgicos/farmacología , Inhibidores Enzimáticos/farmacología , Regulación de la Expresión Génica/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Nifedipino/farmacología , Piridinas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor Muscarínico M2/genética , Receptor Muscarínico M2/metabolismo , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/metabolismo , Receptores Purinérgicos P2X1/genética , Receptores Purinérgicos P2X1/metabolismo , Enfermedades de la Vejiga Urinaria/patología , Quinasas Asociadas a rho/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Obesity is associated with deterioration in asthma outcomes. Although airways eosinophil accumulation is characteristic of lung allergic diseases, little is known about the influence of obesity on the allergic eosinophil trafficking from bone marrow to lung tissues, and recruitment to airways lumen. Here, we have assessed the effects of diet-induced obesity on allergic eosinophilic inflammation in mice, examining eosinophil trafficking from bone marrow to airways, and production of T(H)1/T(H)2 cytokines. EXPERIMENTAL APPROACH: C57BL/6 mice fed for 10 weeks with standard chow or high-fat diet were sensitized and challenged with ovalbumin. At 24-96 h post-ovalbumin challenge, bronchoalveolar lavage (BAL) fluid, lung tissue and bone marrow were examined. KEY RESULTS: The high-fat-fed mice exhibited increased body weight and epididymal fat, glucose intolerance and alterations in lipid profile compared with the lean mice. Obesity markedly elevated serum leptin and lowered adiponectin levels. Ovalbumin challenge in obese mice promoted a markedly higher eosinophil accumulation in bone marrow and connective tissue surrounding the bronchial and bronchiolar segments. Eosinophil number in BAL fluid of obese mice was lower at 24 and 48 h. Levels of interleukin (IL)-5, eotaxin, tumour necrosis factor-alpha and IL-10 in BAL fluid of obese mice were significantly higher than in lean mice. CONCLUSIONS AND IMPLICATIONS: Diet-induced obesity enhanced eosinophil trafficking from bone marrow to lung tissues, and delayed their transit through the airway epithelium into the airway lumen. Consequently, eosinophils remain longer in lung peribronchiolar segments due to overproduction of T(H)1/T(H)2 cytokines and chemokines.
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Asma/inmunología , Eosinófilos/inmunología , Pulmón/inmunología , Animales , Asma/patología , Médula Ósea/inmunología , Bronquios/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Quimiocina CCL11 , Citocinas/biosíntesis , Citocinas/inmunología , Citocinas/farmacología , Eosinofilia/inmunología , Eosinofilia/patología , Hipersensibilidad/inmunología , Hipersensibilidad/patología , Inflamación/inmunología , Inflamación/patología , Interleucina-10/inmunología , Interleucina-10/farmacología , Interleucina-5/inmunología , Interleucina-5/farmacología , Pulmón/efectos de los fármacos , Pulmón/patología , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/inmunología , Obesidad/patología , Ovalbúmina/inmunología , Ovalbúmina/farmacología , Neumonía/inmunología , Neumonía/patología , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence) in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer) were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis) and D2-40 (marker for lymphatic endothelium). Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 µm²; P = 0.019) and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041) when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.
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Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Adenomatosos/patología , Neoplasias Colorrectales/patología , Linfangiogénesis/fisiología , Neovascularización Patológica/patología , Pólipos Adenomatosos/irrigación sanguínea , Pólipos Adenomatosos/química , Anticuerpos Monoclonales/análisis , Antígenos CD/análisis , Biomarcadores/análisis , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/química , Inmunohistoquímica , Vasos Linfáticos/química , Vasos Linfáticos/patología , Microcirculación , Estudios Retrospectivos , Receptores de Superficie Celular/análisisRESUMEN
Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence) in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer) were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis) and D2-40 (marker for lymphatic endothelium). Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 microm(2); P = 0.019) and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041) when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.
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Pólipos Adenomatosos/patología , Neoplasias Colorrectales/patología , Linfangiogénesis/fisiología , Neovascularización Patológica/patología , Pólipos Adenomatosos/irrigación sanguínea , Pólipos Adenomatosos/química , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/análisis , Anticuerpos Monoclonales de Origen Murino , Antígenos CD/análisis , Biomarcadores/análisis , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/química , Endoglina , Femenino , Humanos , Inmunohistoquímica , Vasos Linfáticos/química , Vasos Linfáticos/patología , Masculino , Microcirculación , Persona de Mediana Edad , Receptores de Superficie Celular/análisis , Estudios RetrospectivosRESUMEN
BACKGROUND: Mycosis fungoides (MF) is the most common skin lymphoid neoplasm. In initial stages, differential diagnosis of MF from other benign dermal lymphoid infiltrates (BDLI) may be impossible on morphological basis alone. In previous studies, only deletion of CD7 in MF proved to be of diagnostic help, but not the ratio between immunoexpression of CD4 and CD8. METHODS: 30 cases of MF and 11 cases of BDLI were analysed, in order to compare morphometric parameters, which could be of diagnostic aid. As CD7 is frequently deleted in MF, immunohistochemical detection of T-cells was made using an antibody to CD3. Images of 100 CD3-positive cells per case in both groups were captured and analysed using a simple computer program for nuclear perimeter, area, diameter and nuclear contour index. RESULTS: All parameters showed statistically significant higher values for MF. Area was the variable with the strongest discriminating power between the two groups of patients. Thus even if morphological evaluation is not accurate to distinguish benign versus malignant dermal lymphoid infiltrates, due to the variability of size and shape of these cells, a more sensitive method promptly shows this difference. CONCLUSION: Results suggest that morphometry of CD3-positive lymphoid cells may add valuable information in the differential diagnosis of MF and benign dermatoses.
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Biomarcadores de Tumor/metabolismo , Complejo CD3/metabolismo , Micosis Fungoide/diagnóstico , Neoplasias Cutáneas/diagnóstico , Antígenos de Neoplasias/metabolismo , Núcleo Celular/patología , Diagnóstico Diferencial , Humanos , Micosis Fungoide/ultraestructura , Estudios Retrospectivos , Sensibilidad y Especificidad , Enfermedades de la Piel/diagnóstico , Neoplasias Cutáneas/ultraestructuraRESUMEN
AIMS/HYPOTHESIS: Diet-induced obesity (DIO) is associated with insulin resistance in liver and muscle, but not in adipose tissue. Mice with fat-specific disruption of the gene encoding the insulin receptor are protected against DIO and glucose intolerance. In cell culture, glutamine induces insulin resistance in adipocytes, but has no effect in muscle cells. We investigated whether supplementation of a high-fat diet with glutamine induces insulin resistance in adipose tissue in the rat, improving insulin sensitivity in the whole animal. MATERIALS AND METHODS: Male Wistar rats received standard rodent chow or a high-fat diet (HF) or an HF supplemented with alanine or glutamine (HFGln) for 2 months. Light microscopy and morphometry, oxygen consumption, hyperinsulinaemic-euglycaemic clamp and immunoprecipitation/immunoblotting were performed. RESULTS: HFGln rats showed reductions in adipose mass and adipocyte size, a decrease in the activity of the insulin-induced IRS-phosphatidylinositol 3-kinase (PI3-K)-protein kinase B-forkhead transcription factor box 01 pathway in adipose tissue, and an increase in adiponectin levels. These results were associated with increases in insulin-stimulated glucose uptake in skeletal muscle and insulin-induced suppression of hepatic glucose output, and were accompanied by an increase in the activity of the insulin-induced IRS-PI3-K-Akt pathway in these tissues. In parallel, there were decreases in TNFalpha and IL-6 levels and reductions in c-jun N-terminal kinase (JNK), IkappaB kinase subunit beta (IKKbeta) and mammalian target of rapamycin (mTOR) activity in the liver, muscle and adipose tissue. There was also an increase in oxygen consumption and a decrease in the respiratory exchange rate in HFGln rats. CONCLUSIONS/INTERPRETATION: Glutamine supplementation induces insulin resistance in adipose tissue, and this is accompanied by an increase in the activity of the hexosamine pathway. It also reduces adipose mass, consequently attenuating insulin resistance and activation of JNK and IKKbeta, while improving insulin signalling in liver and muscle.
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Suplementos Dietéticos , Glutamina/farmacología , Insulina/fisiología , Hígado/fisiología , Músculo Esquelético/fisiología , Obesidad/fisiopatología , Transducción de Señal/fisiología , Animales , Peso Corporal/efectos de los fármacos , Dieta , Glucosa/metabolismo , Glucógeno/biosíntesis , Lípidos/biosíntesis , Hígado/efectos de los fármacos , Masculino , Músculo Esquelético/efectos de los fármacos , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: It is controversial if urothelial carcinoma of the bladder with squamous and/or glandular differentiation is a more aggressive neoplasm than conventional urothelial carcinoma. DESIGN: A total of 165 transurethral resections of the bladder were reviewed. A group with squamous and/or glandular differentiation was compared to a group without this finding. The chi-square test was used to assess the association of the groups with stage (TNM, 1997). RESULTS: Of the total of 165 transurethral resections of the bladder, 153 (92.72%) were conventional urothelial carcinomas and 12 (7.27%) showed squamous and/or glandular differentiation. The distribution according to stage was 84 (54.9%), 35 (22.9%) and 34 (22.2%) for the group without differentiation and 0 (0%), 3 (25%) and 9 (75%) for the group with squamous and/or glandular differentiation, respectively for stages pTa, pT1 and pT2. Tumors with squamous and/or glandular differentiation showed a significant statistical correlation to higher stage at clinical presentation (p < 0.0001). There was no significant statistical relation according to age (p = 0.8433), sex (p = 0.5672) or race (p = 0.3137). CONCLUSIONS: The results suggest that urothelial bladder carcinomas with squamous and/or glandular differentiation are more aggressive neoplasms. There was a significant statistical correlation between tumors with this differentiation and higher stage at clinical presentation.
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Carcinoma de Células Escamosas/patología , Neoplasias de la Vejiga Urinaria/patología , Humanos , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
We investigated the effects of hippocampal lesions with ibotenic acid (IBO) on the memory of the sound-context-shock association during reexposure to the conditioning context. Twenty-nine adult pigeons were assigned to a non-lesioned control group (CG, N = 7), a sham-lesioned group (SG, N = 7), a hippocampus-lesioned experimental group (EG, N = 7), and to an unpaired nonlesioned group (tone-alone exposure) (NG, N = 8). All pigeons were submitted to a 20-min session in the conditioning chamber with three associations of sound (1000 Hz, 85 dB, 1 s) and shock (10 mA, 1 s). Experimental and sham lesions were performed 24 h later (EG and SG) when EG birds received three bilateral injections (anteroposterior (A), 4.5, 5.25 and 7.0) of IBO (1 µl and 1 µg/µl) and SG received one bilateral injection (A, 5.25) of PBS. The animals were reexposed to the training context 5 days after the lesion. Behavior was videotaped for 20 min and analyzed at 30-s intervals. A significantly higher percent rating of immobility was observed for CG (median, 95.1; range, 79.2 to 100.0) and SG (median, 90.0; range, 69.6 to 95.0) compared to EG (median, 11.62; range, 3.83 to 50.1) and NG (median, 7.33; range, 6.2 to 28.1) (P<0.001) in the training context. These results suggest impairment of contextual fear in birds who received lesions one day after conditioning and a role for the hippocampus in the modulation of emotional aversive memories in pigeons
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Animales , Condicionamiento Clásico/fisiología , Agonistas de Aminoácidos Excitadores/farmacología , Miedo/fisiología , Hipocampo/lesiones , Hipocampo/fisiología , Ácido Iboténico/farmacología , Aprendizaje/fisiología , Memoria/fisiología , Encéfalo/citología , Columbidae , Señales (Psicología) , Hipocampo/citología , Hipocampo/efectos de los fármacosRESUMEN
We investigated the effects of hippocampal lesions with ibotenic acid (IBO) on the memory of the sound-context-shock association during reexposure to the conditioning context. Twenty-nine adult pigeons were assigned to a non-lesioned control group (CG, N = 7), a sham-lesioned group (SG, N = 7), a hippocampus-lesioned experimental group (EG, N = 7), and to an unpaired nonlesioned group (tone-alone exposure) (NG, N = 8). All pigeons were submitted to a 20-min session in the conditioning chamber with three associations of sound (1000 Hz, 85 dB, 1 s) and shock (10 mA, 1 s). Experimental and sham lesions were performed 24 h later (EG and SG) when EG birds received three bilateral injections (anteroposterior (A), 4.5, 5.25 and 7.0) of IBO (1 microl and 1 microg/microl) and SG received one bilateral injection (A, 5.25) of PBS. The animals were reexposed to the training context 5 days after the lesion. Behavior was videotaped for 20 min and analyzed at 30-s intervals. A significantly higher percent rating of immobility was observed for CG (median, 95.1; range, 79.2 to 100.0) and SG (median, 90.0; range, 69.6 to 95.0) compared to EG (median, 11.62; range, 3.83 to 50.1) and NG (median, 7.33; range, 6.2 to 28.1) (P<0.001) in the training context. These results suggest impairment of contextual fear in birds who received lesions one day after conditioning and a role for the hippocampus in the modulation of emotional aversive memories in pigeons.