RESUMO
The effect of an i. v. infusion of somatostatin (SRIH) 4.1 µg/min×90 min on the basal secretion of NPY and on the NPY response to physical exercise was studied in normal men. Basal NPY secretion was not modified by SRIH infusion, whereas the NPY response to physical exercise was significantly lower in the presence of SRIH. These data suggest the involvement of a somatostatinergic mechanism in the regulation of NPY response to physical exercise.
Assuntos
Exercício Físico , Neuropeptídeo Y/sangue , Somatostatina/metabolismo , Adulto , Regulação para Baixo , Humanos , Infusões Intravenosas , Masculino , Somatostatina/administração & dosagem , Adulto JovemRESUMO
To establish whether ethanol and/or endogenous opioids play a role in the control of arginine-vasopressin (AVP) response to physical exercise, six healthy men underwent six bicycle-ergometer tests until exhaustion [exercise control test; exercise plus ethanol (50 of 110 ml proof whiskey orally), exercise plus naloxone (2 mg injected plus 5 mg infused or 4 mg injected plus 10 mg infused intravenously] or exercise plus ethanol plus naloxone). Plasma AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During the control test, exercise significantly increased plasma AVP levels, with a peak value five times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was abolished by ethanol. When ethanol tests were repeated in the presence of naloxone, at both lower and higher dose, ethanol inhibition on AVP secretion was only partial, with mean peak responses 2.5 times higher than basal values. Results indicate an ethanol involvement in regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying ethanol inhibitory action, but not in mediation of the AVP response to physical exercise.
Assuntos
Arginina Vasopressina/metabolismo , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Exercício Físico/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Adulto , Arginina Vasopressina/sangue , Pressão Sanguínea/efeitos dos fármacos , Dióxido de Carbono/metabolismo , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Consumo de Oxigênio/efeitos dos fármacos , Ventilação Pulmonar/efeitos dos fármacos , Respiração/efeitos dos fármacos , Volume de Ventilação Pulmonar/efeitos dos fármacos , Fatores de Tempo , Adulto JovemRESUMO
AIM: The aim of this study was to test the possibility of enhancing blood calcium levels in totally thyroidectomized patients by supplementation with 1 L/d carbonate-bicarbonate-high-calcium mineral water. METHODS: This study enrolled 95 outpatients, totally thyroidectomized four months earlier, and hence treated with oral calcium and vitamin-D. At recruitment, ionized blood calcium was either below (Group A; N. 55) or above (Group B; N. 40, randomly divided in Group B1 [N. 20] and Group B2 [N.20]) the lower limit of the normal range (1.12 mmol/L). For one month, Group A was treated with 1 L/d high-calcium (483 mg/L) mineral water and continued the usual therapy with Ca and vitamin-D. In contrast, Group B1 and Group B2 substituted their Ca and vitamin-D therapy with 1 L/d high-calcium mineral water (Group B1) or 1 L/d of placebo mineral water (Ca:80 mg/L) (Group B2). RESULTS: After one month, a significant 7.5% increase in blood ionized-calcium levels was observed in Group A, no change in Group B1 and a significant drop below normality in Group B2 (Group B2 vs Group B1, P<0.001). Thereafter, 1 L/d of the high-calcium mineral water, given to Group B2 instead of placebo for an additional month, significantly enhanced ionized-calcium levels above the lower limit of normality (Group B2 vs Group B1, NS). CONCLUSION: These experiments show that calcium supplementation as 1 L/d of a high-calcium mineral water may efficaciously enhance blood calcium levels in thyroidectomized patients. This complementary treatment might at least in part contribute to the prevention and/or treatment of hypocalcemia and substitute vitamin-D and calcium therapies after thyroidectomy.
Assuntos
Cálcio/uso terapêutico , Hipocalcemia/tratamento farmacológico , Águas Minerais/uso terapêutico , Tireoidectomia/efeitos adversos , Adulto , Calcitriol/administração & dosagem , Calcitriol/uso terapêutico , Cálcio/administração & dosagem , Cálcio/sangue , Compostos de Cálcio/administração & dosagem , Compostos de Cálcio/uso terapêutico , Carbonatos/administração & dosagem , Carbonatos/uso terapêutico , Estudos Cross-Over , Relação Dose-Resposta a Droga , Feminino , Bócio/cirurgia , Humanos , Hipocalcemia/sangue , Hipocalcemia/etiologia , Hipoparatireoidismo/sangue , Hipoparatireoidismo/etiologia , Lactatos/administração & dosagem , Lactatos/uso terapêutico , Masculino , Águas Minerais/análise , Hormônio Paratireóideo/sangue , Hormônios Tireóideos/sangue , Tireotropina/sangue , Tiroxina/uso terapêuticoRESUMO
Changes in estrogen receptor (ER) expression and function may explain the development of tamoxifen resistance in breast cancer. ER expression was measured by an immunohistochemical assay, validated for use in tamoxifen-treated tumors against a biochemical enzyme immunoassay, in 72 paired biopsies taken before treatment and at progression or relapse on tamoxifen. Progesterone receptor (PgR) and pS2 gene expression were also measured immunohistochemically as an indicator of ER function. Overall the frequency of ER expression was reduced from 37 of 72 (51%) pretamoxifen to 21 of 72 (29%) at progression or relapse, with a significant reduction in the quantitative level of ER (P < 0.0001; Wilcoxon signed rank sum test). Tumors treated with primary tamoxifen that responded but then developed acquired resistance frequently remained ER positive (ER+) at relapse: 16 of 18 (89%) were ER+ pretamoxifen (75% of these expressed either PgR or pS2) and 11 of 18 (61%) were ER+ at relapse (82% continued to express PgR or pS2). In contrast, only 3 of 20 (15%) tumors that progressed on primary tamoxifen with de novo resistance were ER+ pretamoxifen, and all tumors were ER- at progression. At progression, 6 of 20 (30%) of these tumors expressed high levels of PgR (mean H-score, 98) and/or pS2 (mean, 50% cells positive), despite being ER-. In tumors that recurred during adjuvant tamoxifen therapy, including locoregional and metastatic lesions, ER expression was significantly reduced from 18 of 34 (53%) in the original primary tumor to 10 of 34 (29%) at relapse (P = 0.002). PgR expression was likewise significantly reduced in this group (P = 0.001). This study confirms that expression of a functional ER in breast cancer is a strong predictor for primary response to tamoxifen. Although ER was reduced in tamoxifen-resistant tumors overall, the development of acquired resistance was associated with maintained ER expression and function in many tumors, whereas de novo resistance remained related to lack of ER expression. Recurrence during adjuvant tamoxifen was associated with development of an ER/PgR-negative phenotype in some tumors. These data imply that separate mechanisms of resistance may occur in these different clinical subgroups.
Assuntos
Neoplasias da Mama/química , Proteínas de Neoplasias/análise , Proteínas , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Tamoxifeno/uso terapêutico , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Resistência a Medicamentos , Feminino , Humanos , Imunoensaio , Imuno-Histoquímica , Recidiva Local de Neoplasia/química , Fator Trefoil-1 , Proteínas Supressoras de TumorRESUMO
AIM: To validate the use of a new mouse monoclonal antibody (1D5) directed against the N-terminal domain (A/B region) of the oestrogen receptor in an immunohistochemical assay (ER-IHA) for paraffin wax embedded tissue. METHODS: Breast cancer specimens were surgically obtained from 119 previously untreated patients. For comparison, oestrogen receptor was measured from cytosol fractions using an established oestrogen receptor enzyme immunoassay (ER-EIA) method. Oestrogen receptor "H-scores" were obtained from the ER-IHA after antigen retrieval using microwave treatment. Where discrepancies occurred between the two methods, further immunohistochemistry was performed using the H222 antibody from the Abbott Laboratories ER-ICA kit. RESULTS: The correlation between the two methods was non- linear, but despite this there was an 86% concordance between ER-EIA and ER-IHA using the 1D5 ER antibody. Fifty four per cent of tumours (64/119) were oestrogen receptor positive and 32% (38/119) were negative by both assays. A mismatch between the ER-EIA and ER-IHA occurred in 17 cases. Seven tumours were IHA positive but EIA+, but five of these were borderline negative by EIA, having values of > 5 and < 10 fmol/mg protein. Ten tumours were IHA negative and EIA+; four of these tumours were completely negative by IHA in the section studied. A further IHA assay, carried out on the 17 tumour mismatches with H222 antibody, showed that three tumours remained substantially discordant. These three tumours were strongly positive with the 1D5 antibody and negative with the H222 antibody. Two of these discordant tumours were of the rare ER negative and PgR positive phenotype and may contain oestrogen receptor that is of biological interest but which lacks the hormone binding epitope. CONCLUSIONS: The concordance between the classic enzyme immunoassay technique and the new immunohistochemical method on paraffin wax embedded sections was good. Moreover, the IHA technique using the 1D5 antibody against the N-terminal was easily reproducible. This technique may allow oestrogen receptor content to be determined in large cohorts of patients in whom archival tumour material is available.
Assuntos
Neoplasias da Mama/química , Imuno-Histoquímica/métodos , Receptores de Estrogênio/análise , Adulto , Idoso , Anticorpos Monoclonais , Carcinoma Ductal de Mama/química , Feminino , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Inclusão em Parafina , Receptores de Estrogênio/imunologiaRESUMO
The aim of this study was to investigate the behavior of young subjects towards cigarette smoking. We selected two homogeneous samples of about 500 people from the student population high schools in two Italian cities, Reggio Emilia in the north and Catania in the south. The students were given a questionnaire containing 23 principal questions regarding the social-familial environment, the habit of smoking, the habit as it related to the social environment, the correlations between smoking and health, and the possible behavior towards smoking and smokers. The observed findings were processed with the time-sharing General Electric system, using a modified statistical package.
Assuntos
Fumar , Adolescente , Adulto , Fatores Etários , Criança , Métodos Epidemiológicos , Feminino , Humanos , Itália , Masculino , Fatores SocioeconômicosRESUMO
Two hundred and fifty bone marrow and 140 lymph nodal biopsies were analyzed immunocytochemically, using a mouse monoclonal antibody b-12 (M Ab b-12), which reacts with MCA (mucinous-like carcinoma-associated antigen). The presence of MCA in bone marrow specimens was demonstrated in 102 out of 105 (97.1%) breast cancer metastases, 5 out of 8 (62.5%) gastric cancers, 5 out of 6 (83.3%) colon cancers, 3 out of 5 (60%) prostate cancers, 11 out of 26 (42.3%) lung cancers and 25 out of 30 (83.3%) unknown primary cancers, while no positivity to anti-MCA antibody was found in 30 cases of normal bone marrow biopsies, 5 cases of non epithelial malignancies and 30 cases of hemolymphoproliferative disease. Normal lymph nodes and non-epithelial lymph node metastases did not show any reaction to M Ab b-12; on the contrary MCA positive staining was observed in 75 out of 75 (100%) lymph nodal metastases in breast cancer. These results suggest that application of M Ab b-12 in immunohistochemistry is valid for the detection of bone marrow and lymph nodal micrometastases of epithelial origin.
Assuntos
Antígenos de Neoplasias/metabolismo , Antígenos Glicosídicos Associados a Tumores , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/imunologia , Anticorpos Monoclonais , Medula Óssea/imunologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/secundário , Estudos de Avaliação como Assunto , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática/imunologiaRESUMO
The topographic distribution of a mucinous-like cancer antigen (MCA) recognized by a monoclonal antibody b-12 (MAb b-12) was assessed in benign (38) and malignant (66) breast tissues. The reactivity of MAb b-12 showed a good selectivity for breast tissues, reacting both with normal tissues and breast cancer. The degree of MCA expression was evaluated in the various groups of breast pathology adopting quantitative criteria of assessment. With the criteria of evaluation adopted, strong staining was observed in 71.4% breast carcinomas. The most positive reaction was demonstrated in mucinous carcinoma. MCA distribution in breast tissue was compared with the distribution of two other antigens, CEA and TPA. Reactivity of MAb b-12 was higher than the reactivity shown by the anti-CEA and anti-TPA antibodies.
Assuntos
Antígenos de Neoplasias/metabolismo , Antígenos Glicosídicos Associados a Tumores , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/imunologia , Anticorpos Monoclonais , Doenças Mamárias/imunologia , Doenças Mamárias/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Antígeno Carcinoembrionário/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Peptídeos/imunologia , Peptídeos/metabolismo , Antígeno Polipeptídico TecidualRESUMO
The immunocytochemical phenotype was evaluated in a case of Merkel cell carcinoma of the skin. Intermediate filaments, i.e. neurofilament, glial fibrillary acid protein, cytokeratins, keratin and panfilament as well as S-100 protein, calcitonin and epithelial membrane antigen were detected by immunoperoxidase methods. Nodular positivity for neurofilament was observed. The remaining intermediate filaments and other markers were negative. Thus the origin of Merkel cell carcinoma appears uncertain and this tumor probably has neuroendocrine activity.
Assuntos
Carcinoma de Célula de Merkel/ultraestrutura , Neoplasias Cutâneas/ultraestrutura , Anticorpos Antineoplásicos , Biomarcadores Tumorais/análise , Calcitonina/análise , Carcinoma de Célula de Merkel/análise , Proteínas do Citoesqueleto/análise , Feminino , Proteína Glial Fibrilar Ácida/análise , Humanos , Imuno-Histoquímica , Filamentos Intermediários/ultraestrutura , Queratinas/análise , Pessoa de Meia-Idade , Neoplasias Cutâneas/análiseRESUMO
The serological tumor marker tissue polypeptide antigen (TPA) and the more recently identified tissue-specific polypeptide antigen (TPS) have been reported to be indicators of the proliferation rate of the tumor. In the present investigation we compared the cytosol level of the two markers with the proliferative activity of the tumor measured using the 3H-thymidine labelling index. The preliminary results presented here show that higher TLI is associated with lower cytosol levels of both TPA and TPS. TPA and TPS in the cytosol were significantly associated. These findings are in agreement with the previously demonstrated association between high TPA cytosol levels and better prognosis in breast cancer. Further studies are ongoing in order to: 1. confirm these findings in a larger patient series; 2. investigate any possible prognostic indication provided by TPS; 3. evaluate any possible biological meaning of the negative association between TPA/TPS and TLI in the cytosol of breast cancer.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Divisão Celular , Peptídeos/análise , Neoplasias da Mama/química , Ciclo Celular , Citosol/patologia , DNA de Neoplasias/biossíntese , Humanos , Cinética , Kit de Reagentes para Diagnóstico , Receptores de Esteroides/análise , Timidina/metabolismo , Antígeno Polipeptídico Tecidual , TrítioRESUMO
The expression of oncogene products related to cell growth (c-erbB-2, c-myc, ras p21, EGFR) was investigated in benign (15 cases) and malignant breast lesions (20 cases) by means of immunohistochemistry using the avidin-biotin-peroxidase technique with polyclonal and monoclonal antibodies. The aim of this study was to evaluate the relationship between the staining positivity and various morphological and biological features, such as tumour type, grading, hormone receptor status and cell kinetic parameters. In benign breast lesions, as expected, the kinetic parameters were low, both for Ki-67 and LI. All the specimens showed a diploid condition (the DI being equal to 1) and we found a limited degree of immunoreactivity for all the growth factors and oncogene products. In breast cancer we studied the distribution of immunohistochemical positivity for EGFR, c-erbB-2, c-myc, ras p21 and Ki-67, which was related to age, nodal status, ER and PgR receptor status, LI, DI and histopathological grading. A significant positive correlation was found both between ras p21 expression and nodal status and ER-ICA positivity. We observed a strong correlation between LI and Ki-67 and an inverse relation between Ki-67 and ER expression. These findings suggest the importance of studying the relationship between prognostic factors which may provide preoperative prediction in the biological behaviour of breast cancer, not only on biopsy specimens, but also on fine needle aspirates.
Assuntos
Neoplasias da Mama/metabolismo , Proteínas Oncogênicas/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Receptores ErbB/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67 , Pessoa de Meia-Idade , Índice Mitótico , Proteínas Nucleares/metabolismo , Proteína Oncogênica p21(ras)/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptor ErbB-2 , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
DNA content was determined by flow cytometry in a series of 51 paired fresh tissue samples of primary colorectal carcinomas and the respective non-neoplastic adjacent mucosa in order to assess the relationship between DNA ploidy and the most commonly used prognostic factors. Aneuploidy was observed in 70.6% of the tumors and more than one aneuploid peak was present in 3.9%. Aneuploid tumor frequency was higher in left (93.3%) and right colon (64.7%) cancers than in rectal carcinomas (60.0%), and multiple aneuploid clones were detected more frequently in men than in women and in patients with advanced disease (Dukes stage D). Non-neoplastic mucosa adjacent to aneuploid tumors showed aneuploidy in 4 out of 51 samples (7.8%). The mucosa adjacent to diploid cancers had only diploid characteristics. Ploidy did not correlate with histological abnormalities. These findings suggest that DNA content as determined by flow cytometry needs further study with adequate follow-up to evaluate possible correlations with relapse-free and overall survival. Furthermore the aneuploidy of non-neoplastic mucosa provides evidence for a field defect in mucosa adjacent to colorectal cancer and supports the concept that this alteration may be of influence on carcinogenesis.
Assuntos
Adenocarcinoma/genética , Aneuploidia , Neoplasias Colorretais/genética , DNA de Neoplasias/análise , Mucosa Intestinal/química , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Citometria de Fluxo , Humanos , Mucosa Intestinal/citologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores SexuaisRESUMO
CEA and TPA were studied in sera and in histologic specimens of 200 patients with benign (77) or malignant (123) breast pathology. The frequency and expression of the two markers was different in benign and in cancer tissues. Histologic positivity and high levels of circulating markers were observed more frequently in cancer patients than in patients with benign disease. Tissue positivity for the two tumor markers did not always correlate with elevated levels of circulating markers. Positive CEA and TPA incidence was higher in tissue samples than in serum samples. In the breast cancer group, among 33 patients with histologic positivity for CEA, only 5 cases had circulating CEA levels higher than 5 ng/ml; among 91 patients with histologic positivity for TPA, only 45 cases showed circulating levels for TPA higher than 95 U/l. These findings confirm that tumor size, secretory characteristics and vascular supply are factors affecting the achievement of high circulating marker levels. Combined marker measurement in serum and tissues can provide more information about the presence of a given tumor marker. A limited evaluation of the prognostic meaning of the study of combined CEA and TPA in sera and in tissues was carried out during the follow-up of 60 evaluable patients. Only 5 patients had cancer relapses in the first 12 months from surgery; in 2 of 5 patients TPA was positive initially and at the time of recurrence, in serum as well as in tissues. Circulating CEA gave negative findings in all relapsed patients; 2 of them showed weak positivity only in the histologic staining at the time of presentation.