RESUMO
BACKGROUND: Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. METHODS: Observational retrospective multicenter study. INCLUSION CRITERIA: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. RESULTS: Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. CONCLUSION: It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here.
Assuntos
Artéria Celíaca/cirurgia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Índice de Massa Corporal , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Duração da Cirurgia , Pancreatectomia/efeitos adversos , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias , Estudos Retrospectivos , Espanha , Resultado do TratamentoRESUMO
BACKGROUND: Chemotherapy-associated liver injury (CALI) is a matter of concern for hepatobiliary surgeons as it can entail postoperative liver failure after an extensive hepatectomy. Recent studies have taken special interest in liver function parameters which can correlate with CALI to decrease this adverse event. Therefore, the current study investigates the usefulness of splenic volume as a biomarker of CALI through a portal hypertension mechanism, in patients with colorectal liver metastases (CRLM). STUDY DESIGN: We carried out a study in patients with CRLM operated on between 2009 and 2014 in our center. All samples of healthy liver were graded for non-alcoholic fatty liver disease (NAFLD) and sinusoidal obstructive syndrome. Computarized tomography scans for spleen volumetry were analyzed for each patient at CRLM diagnosis, after neoadjuvant chemotherapy, 1 and 6 months after resection. RESULTS: A group of 65 consecutive patients with CRLM of large bowel adenocarcinoma submitted to liver resection were included. Patients receiving neoadjuvant chemotherapy had a greater spleen volume increase than those who did not receive treatment (p = 0.053), finding a statistically significant spleen growth in patients with NAFLD (p = 0.036). There was no correlation between spleen enlargement and postoperative complications or average stay. However, survival was decreased in patients with spleen growth and CALI. CONCLUSIONS: Patients who receive neoadjuvant chemotherapy for liver metastasis surgery have a greater splenic volume increase, which correlates with NAFLD and a lower survival.
Assuntos
Adenocarcinoma/terapia , Antineoplásicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Neoplasias Colorretais/patologia , Hepatectomia , Hepatopatia Veno-Oclusiva/patologia , Neoplasias Hepáticas/terapia , Hepatopatia Gordurosa não Alcoólica/patologia , Baço/diagnóstico por imagem , Adenocarcinoma/secundário , Antineoplásicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/patologia , Hepatopatia Veno-Oclusiva/induzido quimicamente , Humanos , Neoplasias Hepáticas/secundário , Metastasectomia , Terapia Neoadjuvante , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Tamanho do Órgão , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Complicações Pós-Operatórias , Baço/patologia , Taxa de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Our aim is to find features that define prognosis in surgically resected ductal pancreatic adenocarcinoma readily accessible in everyday practice. MATERIALS AND METHODS: Longitudinal retrospective case series of pancreatic adenocarcinoma operated with a curative intent in a large tertiary hospital in Madrid between 2009 and 2015. RESULTS: 162 were enrolled. 40.8% survived less than 1 year. Multivariate Cox's regression model revealed that gender, presence of symptoms, T and N stage independently influenced progression-free survival, while overall survival was determined by gender, smoking, presence of symptoms and N stage. Logistic regression analysis revealed that only symptoms at diagnosis could predict death, while gender, symptoms, histopathological type, vessel invasion, T stage and necrosis could independently predict recurrence. DISCUSSION: Our series show that patients with symptomatic disease at the time of diagnosis and females showed a shorter progression-free and overall survival. We herein propose a regression model to predict outcome.
Assuntos
Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/patologia , Medicina Molecular , Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/métodos , Adenocarcinoma/cirurgia , Idoso , Carcinoma Ductal Pancreático/cirurgia , Progressão da Doença , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
We present a systematic study of core-shell Au/Fe3O4 nanoparticles produced by thermal decomposition under mild conditions. The morphology and crystal structure of the nanoparticles revealed the presence of Au core of d = (6.9 ± 1.0) nm surrounded by Fe3O4 shell with a thickness of ~3.5 nm, epitaxially grown onto the Au core surface. The Au/Fe3O4 core-shell structure was demonstrated by high angle annular dark field scanning transmission electron microscopy analysis. The magnetite shell grown on top of the Au nanoparticle displayed a thermal blocking state at temperatures below TB = 59 K and a relaxed state well above TB. Remarkably, an exchange bias effect was observed when cooling down the samples below room temperature under an external magnetic field. Moreover, the exchange bias field (HEX) started to appear at T~40 K and its value increased by decreasing the temperature. This effect has been assigned to the interaction of spins located in the magnetically disordered regions (in the inner and outer surface of the Fe3O4 shell) and spins located in the ordered region of the Fe3O4 shell.
RESUMO
Objetivo: Describir la anatomía del proceso uncinado y sus variaciones observadas a través de cortes coronales por tomografía computada multidetector (TCMD) en una población con rinosinusitis crónica. Introducción: Según la literatura científica revisada, no se encontraron estudios sobre las variaciones anatómicas del complejo osteomeatal (COM) en la población adulta colombiana. Los reportes coinciden en que las variaciones anatómicas de este complejo son parte de las causas de la sinusitis crónica refractaria a tratamiento médico, por lo que el presente trabajo se propone estudiar la anatomía de este complejo e identificar sus posibles variaciones anatómicas en pacientes adultos colombianos diagnosticados con sinusitis crónica. Materiales y métodos: Se realizó un estudio descriptivo de corte transversal, observacional y retrospectivo. Para las variables continuas se estimaron medidas de tendencia central y de dispersión, con un intervalo de confianza del 95%, mientras que para las variables categóricas se determinaron las frecuencias y los porcentajes con que se presentaron en la muestra. Resultados: Se contó con 143 casos. De este total, el 53,8% fueron hombres y el 46,2% mujeres. Tanto en el lado derecho como en el izquierdo, el proceso uncinado del hueso etmoides se insertó en la lámina papirácea (el 49,7% y el 53,1% de los hombres y mujeres, respectivamente). La inserción del proceso uncinado en la lámina cribosa del hueso etmoides en el lado derecho fue el segundo en frecuencia (25,2%) y en el lado izquierdo este lugar lo ocupó la inserción en la concha nasal media (23,8%). También se encontró que, en la mayoría de los casos, el proceso uncinado tuvo una orientación lateral (el 51% en el lado derecho y el 56,6% en el lado izquierdo). Conclusión: El proceso uncinado es una estructura anatómica muy variable que se encuentra a cada lado de la cavidad nasal. Presenta diferentes puntos de inserción y tiene cambios en su angulación y distintas longitudes. Es importante tener en cuenta estas variaciones para el manejo quirúrgico de la rinosinusitis crónica.
Objective: To describe the uncinate process anatomy and its variations observed through coronal, multislice computed tomography (MSCT) in patients with chronic rhinosinusitis. Introduction: As reviewed in the literature, no studies of anatomical variations ostiomeatal complex in Colombian adults were found. The reports agree that the anatomical variations of this complex are part of the causes of chronic sinusitis refractory to medical treatment, which motivated the present work to study the anatomy of this complex and identify possible anatomic variations in adult patients from Colombia, diagnosed with chronic sinusitis. Materials and methods: A descriptive, cross-sectional, observational and retrospective study. Continuous variables were estimated with measures of central tendency and dispersion, with a confidence interval of 95%. Categorical variables were determined with frequencies and percentages. Results: The total sample was 143 cases. In the sample, 53.8% were men and 46.2% were women. Both of the right and left, the uncinate process of the ethmoid was inserted into the lamina papyracea in 49.7% and 53.1% of cases, respectively. The insertion of the uncinate process in the cribriform plate of the ethmoid (T6) had a frequency to the right side of 25.2%, but for the left side was the insertion into the middle nasal concha (T1) (23.8%). In most cases, the uncinate process had a lateral orientation and 51% on the right side and 56.6% on the left side. Conclusion: The uncinate process is a highly variable anatomical structure at each side of the nasal cavity, arranged indifferent insertion sites, changes in angle and different lengths which is important from the point of view of surgical management of chronic rinosinusitis.
RESUMO
Objetivo: Describir la anatomía del proceso uncinado y sus variaciones observadas a través de cortes coronales por tomografía computada multidetector (TCMD) en una población con rinosinusitis crónica. Introducción: Según la literatura científica revisada, no se encontraron estudios sobre las variaciones anatómicas del complejo osteomeatal (COM) en la población adulta colombiana. Los reportes coinciden en que las variaciones anatómicas de este complejo son parte de las causas de la sinusitis crónica refractaria a tratamiento médico, por lo que el presente trabajo se propone estudiar la anatomía de este complejo e identificar sus posibles variaciones anatómicas en pacientes adultos colombianos diagnosticados con sinusitis crónica. Materiales y métodos: Se realizó un estudio descriptivo de corte transversal, observacional y retrospectivo. Para las variables continuas se estimaron medidas de tendencia central y de dispersión, con un intervalo de confianza del 95%, mientras que para las variables categóricas se determinaron las frecuencias y los porcentajes con que se presentaron en la muestra. Resultados: Se contó con 143 casos. De este total, el 53,8% fueron hombres y el 46,2% mujeres. Tanto en el lado derecho como en el izquierdo, el proceso uncinado del hueso etmoides se insertó en la lámina papirácea (el 49,7% y el 53,1% de los hombres y mujeres, respectivamente). La inserción del proceso uncinado en la lámina cribosa del hueso etmoides en el lado derecho fue el segundo en frecuencia (25,2%) y en el lado izquierdo este lugar lo ocupó la inserción en la concha nasal media (23,8%). También se encontró que, en la mayoría de los casos, el proceso uncinado tuvo una orientación lateral (el 51% en el lado derecho y el 56,6% en el lado izquierdo). Conclusión: El proceso uncinado es una estructura anatómica muy variable que se encuentra a cada lado de la cavidad nasal. Presenta diferentes puntos de inserción y tiene cambios en su angulación y distintas longitudes. Es importante tener en cuenta estas variaciones para el manejo quirúrgico de la rinosinusitis crónica.(AU)
Objective: To describe the uncinate process anatomy and its variations observed through coronal, multislice computed tomography (MSCT) in patients with chronic rhinosinusitis. Introduction: As reviewed in the literature, no studies of anatomical variations ostiomeatal complex in Colombian adults were found. The reports agree that the anatomical variations of this complex are part of the causes of chronic sinusitis refractory to medical treatment, which motivated the present work to study the anatomy of this complex and identify possible anatomic variations in adult patients from Colombia, diagnosed with chronic sinusitis. Materials and methods: A descriptive, cross-sectional, observational and retrospective study. Continuous variables were estimated with measures of central tendency and dispersion, with a confidence interval of 95%. Categorical variables were determined with frequencies and percentages. Results: The total sample was 143 cases. In the sample, 53.8% were men and 46.2% were women. Both of the right and left, the uncinate process of the ethmoid was inserted into the lamina papyracea in 49.7% and 53.1% of cases, respectively. The insertion of the uncinate process in the cribriform plate of the ethmoid (T6) had a frequency to the right side of 25.2%, but for the left side was the insertion into the middle nasal concha (T1) (23.8%). In most cases, the uncinate process had a lateral orientation and 51% on the right side and 56.6% on the left side. Conclusion: The uncinate process is a highly variable anatomical structure at each side of the nasal cavity, arranged indifferent insertion sites, changes in angle and different lengths which is important from the point of view of surgical management of chronic rinosinusitis.(AU)
RESUMO
The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [(3)H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [(3)H]-DHEAS to [(3)H]-androstenedione, [(3)H]-testosterone, [(3)H]-estrone and [(3)H]-17beta-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E(1)S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [(3)H]-estrone to [(3)H]-17beta-estradiol. This is the first demonstration that human platelets are able to import DHEAS and E(1)S using the OATP family and to convert DHEAS to active DHEA, and to transform E(1)S to 17beta-estradiol.
Assuntos
Plaquetas/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Estrona/análogos & derivados , Androgênios/metabolismo , Androstenodiona/metabolismo , Plaquetas/química , Desidroepiandrosterona/metabolismo , Estradiol/metabolismo , Estrona/metabolismo , Humanos , Transportadores de Ânions Orgânicos/metabolismo , Testosterona/metabolismoRESUMO
The steroid hormone dehydroepiandrosterone (DHEA), suggested to be a cardioprotector, prevents platelet aggregation in healthy humans. This hormone is reduced in postmenopausal women by 60% of its normal value. Platelets in patients with type 2 diabetes (T2D) are more sensitive to aggregation, which has been attributed to a reduced ability to produce nitric oxide (NO). In light of these precedents and considering that DHEA is able to increase the production of NO in cultured endothelial cells, we suggest that DHEA prevents the aggregation of platelet from postmenopausal women with T2D through the activation of PKC/eNOS/NO/cGMP pathway. To determine the effect of DHEA in platelet aggregation, platelet-rich plasma (PRP) obtained from postmenopausal women with T2D was preincubated with DHEA, and aggregation induced by ADP was determined in the presence or absence of L-NNA (LNG-nitroarginine), Rottlerin, NOS, or PKC delta inhibitors, respectively. Platelet NO production was measured with the fluorescent probe DAF2DA and eNOS activation was determined by Western blot, using an anti-p-eNOS (ser 1177) antibody. DHEA 1) prevented platelet aggregation by 40% compared to control, 2) increased NO production by 63%, 3) increased p-eNOS (phosphorylated endothelial nitric oxide synthase) levels, and 4) increased cGMP production. These effects were reduced in the presence of L-NNA or Rottlerin. DHEA prevents platelet aggregation induced by ADP. This effect is mediated by the activation of the PKCδ/eNOS/NO/cGMP pathway. Our results suggest that DHEA could be considered to be a potential therapeutic tool in the prevention of atherothrombotic processes in postmenopausal women with T2D.
Assuntos
Desidroepiandrosterona/farmacologia , Diabetes Mellitus Tipo 2/enzimologia , Óxido Nítrico Sintase Tipo III/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismo , Proteína Quinase C-delta/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/enzimologia , GMP Cíclico/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Fosfosserina/metabolismo , Proteína Quinase C-delta/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacosRESUMO
The changes in endometrial homeostasis found in women with polycystic ovarian syndrome (PCOS) could be associated with alterations in the intracrine metabolism of steroid hormones. The uptake of dehydroepiandrosterone-sulphate (DHEA-S), precursor of the intracrine pathway, is achieved by transporters, such as organic anion transporter polypeptides (OATPs), and molecules with oestrogenic activity, such as androst-5-ene-3beta,17beta-diol (androstenediol), can be generated. We aimed to determine androstenediol generation and the expression of OATPs in human endometria throughout the menstrual cycle and in endometria from PCOS women. Endometrial samples were obtained from control women in the proliferative phase (control endometria (CEp), n=7), secretory phase (CEs, n=7), and from PCOS patients (PCOSEp, n=7). The mRNA levels of OATP-B, OATP-D and OATP-E were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and protein levels of OATP-E by immunofluorescence; 3beta-hydroxysteroid dehydrogenase (HSD) by immunohistochemistry/Western blot; the metabolism of DHEA to androstenediol was evaluated by thin layer chromatography-high-performance liquid chromatography (TLC-HPLC). Lower levels of OATP-E transcript were obtained in PCOSEp (p<0.05) compared with CEp, while OATP-E protein levels (p<0.05) and DHEA conversion to androstenediol (p<0.01) were higher in PCOSEp. Lower 3beta-(hydroxysteroid dehydrogenase) HSD protein levels were found in PCOSEp (p<0.05) (Western blot, immunohistochemistry). These results reveal a higher capacity of the endometria from PCOS women to metabolise DHEA to androstenediol, which, coupled with the high oestrogen sensitivity previously found in these endometria, may account for the increase in cell proliferation in PCOSEp already reported.
Assuntos
Androstenodiol/metabolismo , Desidroepiandrosterona/metabolismo , Endométrio/metabolismo , Síndrome do Ovário Policístico/metabolismo , 3-Hidroxiesteroide Desidrogenases/metabolismo , Adulto , Feminino , Humanos , Ciclo Menstrual/metabolismo , Transportadores de Ânions Orgânicos/genética , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/fisiopatologia , Síndrome do Ovário Policístico/terapia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ácidos Sulfúricos/metabolismoRESUMO
The aim of the present investigation was to study whether the endocrinological status of women bearing polycystic ovarian syndrome (PCOS) affects the endometrial in situ steroid metabolism. For this purpose, we evaluated the mRNA levels (RT-PCR), and the activity of steroid metabolic enzymes: P450 aromatase, steroid sulfatase (STS), estrogen sulfotransferase (EST) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in 23 samples of normal endometria (CE), 18 PCOS endometria without treatment (PCOSE), 10 specimens from PCOS women with endometrial hyperplasia (HPCOSE), and 7 endometria from patients with endometrial hyperplasia not associated to PCOS (EH). The data showed lower levels of STS mRNA for PCOSE and HPCOSE (p<0.05, p<0.01, respectively) and of EST for HPCOSE and EH compared to control (p<0.05). However, higher levels for EST mRNA were obtained in PCOSE (p<0.05) versus CE. The mRNA and protein levels for P450 aromatase were undetectable in all analyzed endometria. The relationship between the activities of STS and EST was lower in PCOSE and HPCOSE (p<0.05) versus CE. The ratio between the mRNA from 17beta-HSD type 1/type 2 was higher in PCOSE (p<0.05), whereas, a diminution in the 17beta-HSD type 2 activity was observed in PCOSE (p<0.05). These results indicate that the activity of enzymes related to the steroid metabolism in analyzed PCOSE differ from those found in the CE. Consequently, PCOSE may present an in situ deregulation of the steroid metabolism.
Assuntos
Hiperplasia Endometrial/patologia , Endométrio/patologia , Estrogênios/metabolismo , Síndrome do Ovário Policístico/patologia , 17-Hidroxiesteroide Desidrogenases/genética , 17-Hidroxiesteroide Desidrogenases/metabolismo , Adulto , Aromatase/genética , Aromatase/metabolismo , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/metabolismo , Endométrio/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esteril-Sulfatase/genética , Esteril-Sulfatase/metabolismo , Sulfotransferases/genética , Sulfotransferases/metabolismoRESUMO
In previous reports we have demonstrated high plasma levels of sex hormone-binding globulin (SHBG) in asymptomatic alcoholic men. In the present work the physicochemical properties of SHBG from plasma of noncirrhotic alcoholic patients have been further compared with SHBG of control subjects. Steroid binding to SHBG was similar for the two groups: alcoholic men, K(d) of 0.62 +/- 0.07 nM and control individuals, K(d) of 0.70 +/- 0.10 nM. The structure of oligosaccharides attached to SHBG from controls and alcoholic men were determined by using serial chromatography. Our data indicated that 7% of SHBG of control individuals was not retarded by the Con-A column, whereas approximately 30% of SHBG of alcoholic men eluted in the void volume of Con A. Approximately 46% of SHBG of alcoholics applied to Con A, possessed biantennary complex oligosaccharides, as indicated by the fact that it could be eluted with methyl-alpha-D-glucopyranoside and by its retention on wheat germ agglutinin; in contrast, when SHBG from control men was analyzed, approximately 51% was eluted with methyl-alpha-D-glucopyranoside. Approximately 9% of the biantennary complex oligosaccharides on SHBG of control men and none of those on SHBG from alcoholic men were fucosylated on the chitobiose core, as determined by chromatography on Lenn culinaris lectin. Galactosylated oligosaccharides were also present on the SHBG fraction as indicated by its interaction with Ricinus communis-I. Approximately 24% of SHBG of alcoholic men and 39% of those on SHBG from control individuals applied to Con-A were retained and could be eluted with methyl-alpha-D-mannopyranoside. Evidence based on the binding on mannoside-eluted SHBG to Con-A, wheat germ agglutinin, and R. communis-I indicated that at least the SHBG in this fraction, from alcoholics or controls, contained two glycosylation sites and that the sites were differentially glycosylated.
Assuntos
Oligossacarídeos/química , Globulina de Ligação a Hormônio Sexual/química , Globulina de Ligação a Hormônio Sexual/metabolismo , Adulto , Fracionamento Químico , Cromatografia de Afinidade , Cromatografia em Agarose , Concanavalina A/metabolismo , Di-Hidrotestosterona/metabolismo , Relação Dose-Resposta a Droga , Humanos , Hepatopatias Alcoólicas/metabolismo , Masculino , Pessoa de Meia-Idade , Ligação Proteica , TrítioRESUMO
We report a 16 year old girl presenting with secondary amenorrhea, a history of voice coarsening, hirsutism and a body mass index of 35 kg/m2. Pelvic ultrasound and CT scans showed a retro uterine dense mass. She was operated and a left ovarian tumor was excised. Pathological examination disclosed a Sertoli-Leydig tumor.
Assuntos
Neoplasias Ovarianas/complicações , Tumor de Células de Sertoli-Leydig/complicações , Adolescente , Amenorreia/etiologia , Índice de Massa Corporal , Feminino , Hirsutismo/etiologia , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Tumor de Células de Sertoli-Leydig/patologia , Tumor de Células de Sertoli-Leydig/cirurgiaRESUMO
Melatonin-binding sites in membrane preparation immature rat testes were demonstrated by utilizing 2-[125I]-iodomelatonin as a radioligand. Binding at these sites was found to be reversible, saturable, specific and of, high affinity. Scatchard analysis of the specific binding revealed an equilibrium binding constant (kd) of 215 +/- 23 pmol/L and a total number of binding sites (Bmax) of 0.94 +/- 0.1 fmol/mg protein. The Hill coefficient of 1.0 suggests a single class of 2-[125I]-iodomelatonin-binding site in the rat testes. The Kd value determined from kinetic analysis was 179 pmol/L, which is in close agreement with the value determined from equilibrium studies. In competition studies, the order of pharmacological affinity for 2-[125I]-iodomelatonin binding sites in the rat membrane testes was: melatonin > 6-hydroxymelatonin > N-acetylserotonin > 5-hydroxyindole-3-acetic acid > 5-hydroxytryptamine > 5-hydroxy-L-tryptophan > tryptamine > > 5-methoxytryptamine, 5-methoxyl-DL-tryptophan, D-L-tryptophan. The 2-[125I]-iodomelatonin binding was markedly reduced by guanine nucleotides; treatment with nonhydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) caused a 10-fold decrease in receptor affinity. In this paper, we report evidence indicating the presence of binding sites in immature rat tests, suggesting a possible direct role of melatonin on testicular steroidogenesis.
Assuntos
Melatonina/análogos & derivados , Melatonina/fisiologia , Testículo/fisiologia , Animais , Sítios de Ligação , Radioisótopos do Iodo , Cinética , Masculino , Melatonina/metabolismo , Ensaio Radioligante , Ratos , Ratos WistarRESUMO
Excessive ethanol ingestion induces hypoandrogenism in male subjects. To confirm its presence and to study its relationship with the degree of liver damage and alcohol abstinence, plasma sex hormones were measured in alcoholic patients without liver failure, after two different abstinence periods. Patients were 30 male chronic alcoholics admitted to the Alcoholism Ward for treatment of their addiction. On admission, we measured: testosterone (T), estradiol (E), follicle stimulating hormone (FSH), luteinizing hormone (LH) and sex-hormone binding globulin (SHBG). A liver biopsy was also performed. These measurements were repeated at discharge and were also done in 15 normal volunteers. On admission (mean abstinence 1.9 +/- 1.7 days) total T was similar to controls, FSH was lower (p < 0.02) and high levels of SHBG were found (3.5 fold increase, as compared to controls). Histologically, 9 patients had normal liver; 14 had moderate alterations and 7 showed marked alterations. Hormonal values were not different in these 3 groups. At discharge, 11.1 +/- 4.7 days after admission, T, E and FSH did not show significant changes but LH decreased (8.2 +/- 5.2 mIU/ml vs 12.9 +/- 4.1, p < 0.001); SHBG also decreased (65.4 +/- 21.6 nmol/l vs 117.2 +/- 33.3, p < 0.001) to values that still were twice those of controls. It is concluded that alcoholic patients without clinical signs of liver failure have normal plasma testosterone levels, irrespective of their histologic liver alterations and high plasma SHBG levels that decreased significantly after a short abstinence. The concomitant LH decrease suggests that hypoandrogenism is likely in these patients. Fast changes in SHBG levels rise the possibility that this protein is candidate marker of alcoholism.
Assuntos
Alcoolismo/sangue , Hormônios Esteroides Gonadais/sangue , Temperança , Adulto , Alcoolismo/patologia , Estudos de Casos e Controles , Humanos , Hepatopatias Alcoólicas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Melatonin binding sites in rat testes interstitial cells were identified using 2-[125I]-iodomelatonin. Saturation studies of cells revealed a single class of high affinity binding sites, with an apparent equilibrium dissociation constant (Kd) of 100 +/- 20 pM, and a total binding capacity (B max) of 3.0 +/- 0.2 x 10(3) melatonin molecules per cell. Binding was reversible and inhibited by non radioactive melatonin. These results suggest that interstitial cells from immature rat testes have specific receptors for melatonin.
Assuntos
Células Intersticiais do Testículo/metabolismo , Melatonina/análogos & derivados , Animais , Sítios de Ligação , Masculino , Melatonina/metabolismo , Ratos , Ratos Wistar , Maturidade Sexual , Testículo/citologia , Testículo/metabolismo , Fatores de TempoRESUMO
Melatonin binding sites in rat testes interstitial cells were identified using 2-[125I]-iodomelatonin. Saturation studies of cells revealed a single class of high affinity binding sites, with an apparent equilibrium dissociation constant (Kd) of 100 +/- 20 pM, and a total binding capacity (B max) of 3.0 +/- 0.2 x 10(3) melatonin molecules per cell. Binding was reversible and inhibited by non radioactive melatonin. These results suggest that interstitial cells from immature rat testes have specific receptors for melatonin
Assuntos
Animais , Masculino , Ratos , Células Intersticiais do Testículo/metabolismo , Melatonina/análogos & derivados , Sítios de Ligação , Melatonina/metabolismo , Ratos Wistar , Maturidade Sexual , Testículo/citologia , Testículo/metabolismo , Fatores de TempoRESUMO
Melatonin disturbs the reproductive process in seasonal but not in continuous breeders: however, it delays sexual development in the rat. The testicular function of rats injected daily with melatonin from 20 up to 25, 30, 35 or 40 days of age was analyzed. The spermatogenic and androgenic activity of testes was assessed by light microscopy and by the capacity for binding hCG and producing testosterone in vitro, respectively. In addition, LH, FSH and testosterone plasma levels were measured and 3B-hydroxysteroid dehydrogenase activity of Leydig cells was assessed histochemically to aid in the interpretation of results. Rats treated with melatonin for 15 or 20 days presented at the end of the juvenile period, abnormal progression of spermatogenesis and decreased ability of their Leydig cells to produce testosterone both in vivo and in vitro. This was associated with a lower number of binding sites for hCG and diminished production of testosterone in response to receptor and post-receptor mediated stimulation of steroidogenesis. Melatonin caused a marked decrease in LH serum levels. The diminished LH supply to the testis probably interfered with differentiation or impaired the functional ability of Leydig cells. As a consequence, testicular testosterone production was insufficient to support normal spermatogenic progression and growth and development of the sexual accessory organs.