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1.
J Int Neuropsychol Soc ; 30(2): 172-182, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37465902

RESUMO

OBJECTIVE: Verbal fluency tests are quick and easy to administer neuropsychological measures and are regularly used in neuropsychological assessment. Additionally, phonological fluency is a widely used paradigm that is sensitive to cognitive impairment. This paper offers normative data of phonological verbal fluency (letters P, M, R) for Spanish middle- and older-aged adults, considering sociodemographic factors, and different measures such as the total number of words, errors (perseveration and intrusions), and 15 sec-segmented scores. METHOD: A total of 1165 cognitively unimpaired participants aged between 50 and 89 years old, participated in the study. Data for P were obtained for all participants. Letters M and R were also administered to a subsample of participants (852) aged 60 to 89 years. In addition, errors and words produced every 15 seconds were collected in the subsample. To verify the effect of sociodemographic variables, linear regression was used. Adjustments were calculated for variables that explained at least 5% of the variance (R2 ≥ .05). RESULTS: Means and standard deviations by age, scaled scores, and percentiles for all tests across different measures are shown. No determination coefficients equal to or greater than .05 were found for sex or age. The need to establish adjustments for the educational level was only found in some of the measures. CONCLUSIONS: The current norms provide clinically useful data to evaluate Spanish-speaking natives from Spain aged from 50 to 89 years. Specific patterns of cognitive impairment can be analyzed using these normative data and may be important in neuropsychological assessment.


Assuntos
Disfunção Cognitiva , Pessoa de Meia-Idade , Humanos , Idoso , Adulto , Idoso de 80 Anos ou mais , Escolaridade , Modelos Lineares , Linguística , Testes Neuropsicológicos
2.
J Nutr Health Aging ; 20(7): 722-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27499305

RESUMO

OBJECTIVES: Attrition is one of the greatest difficulties in longitudinal studies on cognitive ageing because of the associated risk of underestimating declines. The aims of this paper were to characterize the magnitude and selectivity of attrition in a study of mild cognitive impairment. DESIGN: Forty two patients with multiple-domain amnestic MCI, 71 with single-domain amnestic MCI, 35 with non-amnestic MCI and 318 healthy controls were recruited from primary care centers and assessed at baseline. MEASUREMENTS: All participants underwent extensive neuropsychological evaluation, including the Mini-Mental State Examination, the Californian Verbal Learning Test, the CAMCOG-R battery, the Counting Span task and Listening Span task, and the Subjective Memory Complaints Questionnaire. RESULTS: 21.5% of the participants at baseline did not participate in the follow-up assessment. Comparison between respondents and non-returners did not reveal differences in cognitive performance in the MCI group. Data obtained at the initial assessment regarding comorbidity, social activities and attention given to memory training enabled prediction of the status of the participants in the follow-up assessment. CONCLUSION: Identification of potential non- returners is relevant, especially in MCI studies, in order to develop retention strategies to minimize attrition.


Assuntos
Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Testes Neuropsicológicos , Envelhecimento , Atenção , Cognição , Transtornos Cognitivos/diagnóstico , Comorbidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Transtornos da Memória/diagnóstico , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Comportamento Social , Inquéritos e Questionários
3.
Transplant Proc ; 43(10): 4005-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22172889

RESUMO

We present a case of a 45-year-old man who suffered from idiopatic membranoproliferative glomerulonephritis (MPGN) in the native kidney that relapsed after his first and second renal grafts. The patient was diagnosed in 1990 with lobular MPGN type I, receiving his first renal graft in 1996. In 2001, a biopsy showed recurrence of MPGN type I (rMPGN). He underwent a second renal graft in 2008. In January 2010, he experienced increased proteinuria and creatinine. Upon electron microscopy of a renal graft biopsy we diagnosed a new rMPGN. At the time of the biopsy, complement levels were normal, although C3 and C4 decreased further. We administered 12 plasmapheresis (PP) sessions and four doses of rituximab. Due to persistent renal impairment, we performed a new biopsy 3 months later, showing less severity of the acute lessions. He received a new cycle of treatment (PP+rituximab). One year later, his renal function was stable with a creatinine ranging between 2 and 2.5 mg/dL and a protein/creatinine ratio less than 1 mg/mg. We concluded that the treatment stopped the disease progression.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Glomerulonefrite Membranoproliferativa/terapia , Fatores Imunológicos/uso terapêutico , Transplante de Rim/efeitos adversos , Plasmaferese , Biópsia , Progressão da Doença , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Glomerulonefrite Membranoproliferativa/patologia , Glomerulonefrite Membranoproliferativa/cirurgia , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Recidiva , Reoperação , Rituximab , Resultado do Tratamento
6.
Radiologia ; 50(5): 409-15, 2008.
Artigo em Espanhol | MEDLINE | ID: mdl-19055919

RESUMO

OBJECTIVE: To retrospectively analyze the clinical, radiolgical, and histological findings in patients with uterine leiomyomas (LU) that required surgical intervention after embolization. MATERIAL AND METHODS: Between July 1999 and January 2006, we embolized 182 patients with LU. Eight of these patients subsequently required surgical resection of the tumor. We reviewed clinical data, imaging findings, embolization technique, and reasons for surgery, histological findings in the resected specimens, identification and location of the embolizing material, presence and type of necrosis in the LU, and associated pathology in adjacent organs. RESULTS: The 8 patients that required surgery represented 4.3% of all patients embolized for LU. Surgery was necessary due to technical failure in two patients (1.02%), complications in three (1.64%) and failed treatment in the remaining three 3 (1.64%). The mean maximum diameter of the LU was 9.8 cm (range: 4-17 cm). The mean volume of the LU was 491.88 ml (range: 30-1.365 ml) The mean age of the patients was 37.7 years (range: 28-48 years). Global necrosis was evident in 6 LU; necrosis was hyaline type in 3 and inflammatory in the remaining 3. The embolizing material was detected in the LU in one case, in the uterine myometrium in two cases, and in the ovary in one. CONCLUSION: Less than 5% of cases of LU required surgery after embolization; the risk of surgery after embolization was greater in large lesions. When the embolization technique was adequate, histological study confirmed global necrosis of the tumors, although this was not accompanied by clinical improvement.


Assuntos
Embolização Terapêutica , Leiomioma/terapia , Neoplasias Uterinas/terapia , Adulto , Feminino , Humanos , Leiomioma/patologia , Leiomioma/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia
7.
Radiología (Madr., Ed. impr.) ; 50(5): 409-415, sept. 2008. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-79116

RESUMO

Objetivo. Análisis retrospectivo clínico, radiológico y patológico de pacientes con leiomiomas uterinos (LU) que requirieron intervención quirúrgica tras el tratamiento con embolización. Material y métodos. Desde julio de 1999 hasta enero de 2006 se embolizaron 182 pacientes con LU. Del total de ellas, 8 precisaron intervención quirúrgica con extirpación del tumor. Revisamos retrospectivamente, en estas 8 pacientes, datos clínicos, hallazgos de pruebas por imagen, técnica de embolización y causas de la cirugía, hallazgos histológicos en las piezas extirpadas, identificación y localización del material embolizante (ME), presencia y tipo de necrosis en los LU y patología asociada en órganos adyacentes. Resultados. Las 8 pacientes intervenidas representan un 4,3% del total de pacientes embolizadas. La causa fue por fallo técnico en dos (1,02%), complicaciones en tres (1,64%) y fallo en el tratamiento en otras tres (1,64%). La media de los diámetros máximos de los LU fue de 9,8 cm (rango: 4-17 cm). El volumen medio de los LU fue de 491,88 ml (rango: 30-1,365 ml). La edad media de las pacientes fue de 37,7 años (rango: 28-48 años). Histológicamente se evidenció necrosis global en 6 de los LU, siendo de tipo hialino en 3 e inflamatorio en los otros 3. El ME se detectó en el LU (un caso), en el miometrio uterino (dos casos) y en un ovario (un caso). Conclusión. Los casos de LU que requieren cirugía posembolización son inferiores al 5%, existiendo mayor riesgo en los de gran tamaño. Cuando la técnica de embolización fue adecuada, el estudio histológico confirmó la necrosis global de los tumores, aunque este hecho no se acompañó de mejoría clínica (AU)


Objective. To retrospectively analyze the clinical, radiolgical, and histological findings in patients with uterine leiomyomas (LU) that required surgical intervention after embolization. Material and methods. Between July 1999 and January 2006, we embolized 182 patients with LU. Eight of these patients subsequently required surgical resection of the tumor. We reviewed clinical data, imaging findings, embolization technique, and reasons for surgery, histological findings in the resected specimens, identification and location of the embolizing material, presence and type of necrosis in the LU, and associated pathology in adjacent organs. Results. The 8 patients that required surgery represented 4.3% of all patients embolized for LU. Surgery was necessary due to technical failure in two patients (1.02%), complications in three (1.64%) and failed treatment in the remaining three 3 (1.64%). The mean maximum diameter of the LU was 9.8 cm (range: 4-17 cm). The mean volume of the LU was 491.88 ml (range: 30-1.365 ml) The mean age of the patients was 37.7 years (range: 28-48 years). Global necrosis was evident in 6 LU; necrosis was hyaline type in 3 and inflammatory in the remaining 3. The embolizing material was detected in the LU in one case, in the uterine myometrium in two cases, and in the ovary in one. Conclusion. Less than 5% of cases of LU required surgery after embolization; the risk of surgery after embolization was greater in large lesions. When the embolization technique was adequate, histological study confirmed global necrosis of the tumors, although this was not accompanied by clinical improvement (AU)


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Embolização Terapêutica/métodos , Embolização Terapêutica , Leiomioma/patologia , Leiomioma , Miométrio/patologia , Miométrio , Leiomioma/cirurgia , Estudos Retrospectivos , Neoplasias Uterinas , Útero/anatomia & histologia , Útero , Necrose/complicações , Necrose , Cateterismo
8.
Pediatr Dermatol ; 24(6): 640-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18035987

RESUMO

Granulomatous slack skin syndrome is a rare clinical and pathologic disorder. Only 42 patients have been reported, one of whom we described in 1997--the only child so far reported. We now describe the evolution of this patient and the transformation of the disease into a peripheral T-cell lymphoma, and the complications resulting in the child's death.


Assuntos
Linfedema/etiologia , Linfoma Cutâneo de Células T/patologia , Pele/patologia , Adolescente , Adulto , Antígenos CD/análise , Evolução Fatal , Humanos , Imuno-Histoquímica , Linfoma Cutâneo de Células T/complicações , Masculino
9.
J Clin Pathol ; 59(7): 775-8, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16803953

RESUMO

Primary primitive neuroectodermal tumours (PNETs) of the bladder are extremely rare and aggressive neoplasms, and only six examples have been reported in the literature. The case of a 21-year-old woman, who remains disease free 3 years after tumour resection, is reported here. Morphological features were found to correspond to a small round blue cell tumour without rosette formation and with extensive areas of necrosis. Strong expression of CD99, vimentin and CD117 (c-kit), and focal reactivity to cytokeratin and S-100 protein was observed in tumour cells. Ultrastructurally, sparse neurosecretory granules were observed. Diagnosis of PNET was supported by molecular genetic analysis, showing the EWS-FLI-1 fusion transcript type 2 by RT-PCR and EWS gene rearrangement by fluorescence in situ hybridisation. A normal genetically balanced genotype was shown by comparative genomic hybridisation, which, together with the expression of c-kit, a known therapeutic target for imatinib, may have prognostic and therapeutic implications.


Assuntos
Tumores Neuroectodérmicos Primitivos/patologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Feminino , Humanos , Proteínas de Neoplasias/metabolismo , Tumores Neuroectodérmicos Primitivos/genética , Tumores Neuroectodérmicos Primitivos/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteína Proto-Oncogênica c-fli-1/genética , Proteína EWS de Ligação a RNA , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
10.
Histopathology ; 47(1): 101-10, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15982329

RESUMO

AIMS: To describe the features of a series of nine cases of diffuse large B-cell lymphoma (DLBCL) showing morphological and immunophenotypic features that are intermediate with Hodgkin's lymphoma (HL). METHODS AND RESULTS: Most cases (6/9) presented as mediastinal tumours affecting young males, while the other three cases arose in extramediastinal locations. Histopathologically, tumours showed diffuse large cell areas in a polymorphous background, with pleomorphic cytology and the common presence of Hodgkin's and Reed-Sternberg cells. Immunophenotypically, tumours shared features of DLBCL and classical HL, with expression of CD30, CD15 (6/9), and a full B-cell profile including CD45RB, CD20, CD79a and OCT2. Epstein-Barr virus-latent membrane protein expression was found in 2/9 cases. The majority of tumours had immunohistochemical features consistent with activation of the NF-(kappa)B pathway, including nuclear location of the c-REL/p65 subunit, overexpression of phosphorylated I(kappa)B(alpha), and overexpression of NF-(kappa)B targets. Finally, 2/9 cases showed 3q27 (BCL6) rearrangement, and 1/9 had p53 gene mutations, both of which are rarely detected in classical HL. CONCLUSIONS: These findings suggest that DLBCLs with HL features constitute a distinctive subgroup of aggressive lymphomas whose neoplastic growth and peculiar characteristics could be facilitated by a particular microenvironment found in the mediastinum.


Assuntos
Doença de Hodgkin/patologia , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Adulto , Idoso , Antígenos CD/análise , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/genética , Diagnóstico Diferencial , Feminino , Rearranjo Gênico , Doença de Hodgkin/genética , Doença de Hodgkin/metabolismo , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Antígeno Ki-67/análise , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-6 , Fatores de Transcrição/análise , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/genética
11.
Rapid Commun Mass Spectrom ; 16(8): 749-54, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11921258

RESUMO

A variety of 5-alkoxycarbonyl-4-aryl-6-methyl-3,4-dihydro-2(1H)-pyridones and hexahydrofuro[3,4-b]-2(1H)-pyridones have been investigated by electron impact (EI) and electrospray ionisation (ESI) techniques. Sequential product ion fragmentation (MS(n)) was performed to elucidate the degradation pathways for these compounds. Comparisons are made between positive and negative even-electron ions from ESI spectra and the molecular radical cations obtained under EI conditions. The data collected in this paper provide information on the strong impact that different substituents have on the ion fragmentation process.


Assuntos
Piridonas/análise , Cromatografia Gasosa-Espectrometria de Massas , Indicadores e Reagentes , Espectrometria de Massas por Ionização por Electrospray
12.
J Org Chem ; 66(26): 8872-82, 2001 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-11749618

RESUMO

Novel pi-conjugated donor-acceptor chromophores, based on the strong electron-donating tetrathiafulvalene moiety and different electron-withdrawing acceptors, exhibit large second-order optical nonlinearities. The effect of increasing the length of the polyenic spacer and the influence of the nature of the acceptor moiety on the NLO properties have been studied by using the electric field-induced second-harmonic generation (EFISH) technique as well as by semiempirical and ab initio theoretical calculations. A charge-transfer band has been observed in the absorption spectra of these D-pi-A compounds that undergoes an hypsochromic shift when increasing the number of vinylenic spacer units connecting both donor and acceptor moieties. The degree of the intramolecular charge transfer from the donor to the acceptor has also been analyzed by means of Raman spectroscopy.

13.
Clin Endocrinol (Oxf) ; 54(6): 839-42, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11422121

RESUMO

The differential diagnosis of Cushing's syndrome is a major challenge to clinical endocrinologists, especially those infrequent cases referred to as occult ectopic ACTH syndromes. Although bronchial carcinoids are well known to be a cause of Cushing's syndrome due to ectopic ACTH secretion, very few cases of carcinoid tumourlets causing an ACTH ectopic syndrome have been reported, and their origin remains controversial. For some authors, tumourlets and typical carcinoids represent distinct pathological entities, whilst others hold that tumourlets are merely microscopic carcinoid tumours. We report a patient with an aggressive Cushing's syndrome that required bilateral adrenalectomy, diagnosed 22 years before a 3-cm lung nodule became apparent on routine chest X-ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid surrounded by tumourlets. Both tumourlets and carcinoid tumour showed strongly positive ACTH immunostaining. Recently, Arioglu et al. (1998) reported a case of Cushing's syndrome caused by pulmonary carcinoid tumourlets, concluding that this entity should be considered in the differential diagnosis of occult ectopic ACTH syndrome. Furthermore, we consider that the carcinoid tumourlets found in our patient, were the initial source of ACTH, leading to Cushing's syndrome with a rapid onset, and that a loss of cell proliferation control in one of such tumourlets many years later, could have resulted in the development of a typical carcinoid tumour, reinforcing the theory of a common origin of these lesions.


Assuntos
Síndrome de ACTH Ectópico/etiologia , Neoplasias Brônquicas/complicações , Tumor Carcinoide/complicações , Síndrome de ACTH Ectópico/patologia , Síndrome de ACTH Ectópico/cirurgia , Adrenalectomia , Adulto , Neoplasias Brônquicas/patologia , Neoplasias Brônquicas/cirurgia , Tumor Carcinoide/patologia , Tumor Carcinoide/cirurgia , Síndrome de Cushing/complicações , Síndrome de Cushing/patologia , Síndrome de Cushing/cirurgia , Humanos , Masculino
14.
Rapid Commun Mass Spectrom ; 15(10): 758-62, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11344534

RESUMO

The electrospray ionisation (ESI) in negative mode of the pharmacologically significant 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazin-2-thiones, and their subsequent fragmentations using an ion-trap mass spectrometer, have been investigated. Experiments on sequential product ion fragmentations (MS(n)) were performed in order to elucidate the degradation pathways for these compounds. The data presented show that the fragmentation of the even-electron [M - H](-) ions could proceed through an internal nucleophilic substitution displacement. Decarboxylation and extrusion of carbon disulfide are other fragmentations observed.


Assuntos
Espectrometria de Massas por Ionização por Electrospray/métodos , Tiadiazinas/química , Tionas/química , Descarboxilação , Estrutura Molecular
15.
Rapid Commun Mass Spectrom ; 15(1): 20-4, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11135420

RESUMO

Electron impact ionization (EI), chemical ionization (CI), electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) were used to investigate a number of relatively large and structurally related new heterocycles such as substituted 1,4,5,6,7,8-hexahydroquinolines and their oxa-analogues 5,6,7,8-tetrahydro-4H-chromenes. In the EI spectra the hexahydroquinolines undergo the loss of the substituent attached at the C4 position, while the 4H-chromenes undergo a retro-Diels-Alder reaction (RDA) after elimination of the C4 substituent. Under chemical ionization conditions the RDA reaction is observed only for the 4H-chromenes. The ESI-MS/MS spectra reveal results similar to the EI and CI spectra, since the 4H-chromenes undergo RDA reactions while the hexahydroquinolines form a very stable even-electron pyridium ion derived from the loss of the C4 substituent.

16.
Rapid Commun Mass Spectrom ; 14(19): 1783-6, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11006585

RESUMO

New substituted 2-amino-3-cyano-4H-pyrans have been studied by electron ionization (EI), chemical ionization (CI) and electrospray ionization (ESI) mass spectrometry. The retro-Diels-Alder reaction (RDA) is the main fragmentation pattern observed in the EI spectra forming an unsaturated ketone as the diene fragment. In contrast, a different RDA reaction takes place yielding an unsaturated amide as diene fragment together with the unsaturated ketone in the CI spectra. The MS/MS spectra obtained using an ESI source reveal that the favoured fragmentation by collision induced dissociation (CID) is the elimination of the substituent at the C4 position with formation of a stable pyrilium cation.


Assuntos
Piperazinas/química , Piranos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Espectroscopia de Infravermelho com Transformada de Fourier
17.
Rapid Commun Mass Spectrom ; 13(21): 2180-2, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10523778

RESUMO

The electron impact mass spectra of new 5-acetyl-4-aryl-6-methyl-2(1H)pyridones have been studied. A dominant peak in all the spectra is due to cleavage of the CO-NH bond of the amido group with charge retention on the carbonyl group. This fragmentation is followed by a hydrogen rearrangement to the nitrogen atom forming ketene intermediates; this pathway leads to a highly stabilized ion which constitutes the base peak in the spectra in most of the compounds studied. Copyright 1999 John Wiley & Sons, Ltd.

19.
Clin Rheumatol ; 18(1): 61-5, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10088955

RESUMO

Giant cell arteritis most often affects the superficial temporal artery. Arterial territories such as the facial, carotid, myometrial and upper and lower limb arteries may be affected. In this paper we describe the case of a 52-year-old patient with upper and lower limb ischaemia who presented with grade III ischaemia in the left lower limb. Giant cell arteritis was diagnosed as responsible for the symptoms. After treatment with corticoids, an angiographic improvement was evidence after 2-year period. The low number of reported cases, the diverse symptoms and varied course make diagnosis of GCA difficult. Therefore, GCA must be taken into consideration in the ischaemia of inferior and superior limbs whether isolated or simultaneous.


Assuntos
Angiografia , Arterite de Células Gigantes/diagnóstico , Mãos/irrigação sanguínea , Isquemia/diagnóstico por imagem , Perna (Membro)/irrigação sanguínea , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/tratamento farmacológico , Biópsia , Feminino , Artéria Femoral/diagnóstico por imagem , Seguimentos , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Isquemia/tratamento farmacológico , Isquemia/etiologia , Pessoa de Meia-Idade , Artéria Subclávia/diagnóstico por imagem , Artérias Temporais/patologia , Ultrassonografia Doppler
20.
J Gastroenterol Hepatol ; 13(2): 197-207, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10221824

RESUMO

Prostaglandin E1 has hepatoprotective properties in several clinical and experimental models of liver dysfunction. Hepatotoxicity induced by D-galactosamine (D-GalN) is a suitable animal model of human acute hepatic failure. The aim of the study was to investigate if prostaglandin E1 (PGE1) protection against hepatic D-GalN-induced apoptosis was related to tumour necrosis factor-alpha (TNF-alpha) content in serum. This cytokine is associated with in vitro apoptosis and general inflammatory disorders. In this study, PGE1 was administered 30 min before D-GalN to rats. In other experiments, several doses of TNF-alpha were administered 15min after PGE1 to D-Ga1N-treated rats. Several parameters related to apoptosis and necrosis were measured by flow cytometry, gel electrophoresis, biochemical analysis, and optical and electron microscopy. Tumour necrosis factor-alpha was quantified by competitive enzyme-linked immunosorbent assay (ELISA). PGE1 by itself did not modify the cell cycle of hepatocytes and liver toxicity, but increased TNF-alpha in serum in comparison with the control group. D-Galactosamine increased the percentage of hepatocytes in apoptosis and in the S phase of the cell cycle, and decreased those in G0/G1. Such an increase of hepatocytes in apoptosis was correlated with a higher number of apoptotic bodies and DNA fragmentation in liver than control samples. Also, D-GalN increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and TNF-alpha in serum compared with the control group. Pre-administration of PGE1 to D-GalN-treated rats reduced all the parameters of apoptosis and necrosis in liver, and increased additionallyTNF-alpha content in serum. In those experiments where low doses of TNF-alpha were administered to PGE1 and D-GalN-treated rats an inverse relationship appeared between TNF-alpha and ALT content in serum. In conclusion, the protective effects of PGE1 on D-GalN-induced apoptosis may be linked to its capacity to modulate cell division and/or its immunomodulatory activity. In this sense, our experimental results suggest that TNF-alpha could be involved in protection or exacerbation of liver damage in relation to the pathophysiological status of the liver.


Assuntos
Alprostadil/farmacologia , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Galactosamina , Fígado/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Animais , Ciclo Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/patologia , Masculino , Microscopia Eletrônica , Ratos , Ratos Wistar
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