RESUMO
Reduced liver function, increased oxidative stress, and inflammation in early lactation negatively impact lactation performance and health of fresh cows. Previous findings from our group demonstrated that branched-chain amino acids (BCAA) infusion improved lactation performance and branched-chain ketoacids (BCKA) infusion decreased liver triglyceride (TG) in fresh cows. The objectives of this study were to determine the effect of BCAA and BCKA on blood and liver biomarkers of liver function, oxidative stress, and inflammation as well as expression of genes regulating inflammation and antioxidant metabolism in the liver. Thirty multiparous Holstein cows were used in a randomized block design receiving continuous abomasal infusion for 21 d after parturition. Treatments (10 cows each) were control (CON), cows abomasally infused with 0.9% saline; BCA, cows abomasally infused with BCAA (67 g valine, 50 g leucine, and 34 g isoleucine); and BCK, cows abomasally infused with BCKA (77 g ketovaline, 57 g ketoleucine, and 39 g ketoisoleucine). All cows were randomly assigned to treatments after parturition and received the same diet throughout the experimental period. Blood was collected at 3, 7, 14, and 21 d postpartum for liver function, oxidative stress, and inflammation biomarker profiling. Liver was also harvested on 7, 14, and 21 d postpartum for quantification of glutathione, protein carbonylation, and expression of genes. ANOVA was conducted for all data using PROC GLIMMIX in SAS. No treatment differences were observed for liver function biomarkers (bilirubin, gamma-glutamyl transferase, and aspartate aminotransferase). Cows receiving BCAA had lower blood NO2- and NO3- concentrations compared with CON. A tendency for lower advanced oxidized protein products was also observed in BCA cows compared with CON. Additionally, on d 7, BCA cows had lower protein carbonylation in the liver compared with CON. In contrast, BCK cows had higher plasma thiol and albumin, as well as liver reduced and total glutathione compared with CON cows. Compared with CON, BCK cows had higher expression glutathione reductase in the liver. Overall, these results suggest favorable alterations in oxidative stress and inflammation status in fresh cows receiving BCAA or BCKA infusion during the first 3 weeks of lactation, which likely contributed to previously-observed changes in lactation performance and liver TG concentrations. Future work is required to evaluate the interrelated metabolism of BCAA and BCKA to better understand their effects on oxidative and immune metabolism.
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Subclinical ketosis (SCK) may impair white blood cell (WBC) function and thus contribute to the risk of disease postpartum. This preliminary study investigated changes occurring in the immune system before disease onset to elucidate their role in the occurrence of SCK. A group of 13 Holstein dairy cows were housed in tie-stalls and retrospectively divided into 2 groups based on their levels of ß-hydroxybutyrate (BHB) measured in plasma between calving day and 35 d from calving (DFC). Levels of BHB <1.4 mmol/L were found in 7 cows (control cows, CTR group) and levels >1.4 mmol/L were found in 6 cows at ≥1 of 6 time points considered (cows with SCK, KET group). From -48 to 35 DFC, body condition score, body weight, dry matter intake, rumination time, and milk yield were measured, and blood samples were collected regularly to assess the hematochemical profile and test the WBC function by ex vivo challenge assays. Data were submitted for ANOVA testing using a mixed model for repeated measurements that included health status and time and their interactions as fixed effects. Compared with CTR cows, KET cows had more pronounced activation of the immune system (higher plasma concentrations of proinflammatory cytokines, myeloperoxidase, and oxidant species, and greater IFN-γ responses to Mycobacterium avium), higher blood concentrations of γ-glutamyl transferase, and lower plasma concentrations of minerals before calving. Higher levels of nonesterified fatty acids, BHB, and glucose were detected in KET cows than in CTR cows during the dry period. The effect observed during the dry period was associated with a reduced dry matter intake, reduced plasma glucose, and increased fat mobilization (further increases in nonesterified fatty acids and BHB) during early lactation. A reduced milk yield was also detected in KET cows compared with CTR. The KET cows had an accentuated acute-phase response after calving (with greater concentrations of positive acute-phase proteins and lower concentrations of retinol than CTR cows) and impaired liver function (higher blood concentrations of glutamate-oxaloacetate transaminase and bilirubin). The WBC of the KET cows, compared with CTR cows, had a reduced response to an ex vivo stimulation assay, with lower production of proinflammatory cytokines and greater production of lactate. These alterations in the WBC could have been driven by the combined actions of metabolites related to the mobilization of lipids and the occurrence of a transient unresponsive state against stimulation aimed at preventing excessive inflammation. The associations identified here in a small number of cows in one herd should be investigated in larger studies.
Assuntos
Doenças dos Bovinos/imunologia , Cetose/veterinária , Lactação , Ácido 3-Hidroxibutírico/sangue , Animais , Bilirrubina/sangue , Bovinos , Ácidos Graxos não Esterificados/sangue , Feminino , Glucose/metabolismo , Nível de Saúde , Inflamação/veterinária , Mediadores da Inflamação/sangue , Cetose/imunologia , Lipídeos , Leite , Período Pós-Parto , Estudos RetrospectivosRESUMO
BACKGROUND: The percentages of breast cancer cases in a given population attributable to specific risk factors (i.e., the population-attributable risks) can be calculated; determination of such risks associated with potentially modifiable risks factors, such as diet (e.g., levels of consumption of fruits, vegetables, vitamins, etc.), alcohol consumption, exercise, and body weight, are necessary to focus prevention strategies. METHODS: With the use of data from a case-control study conducted in Italy from June 1991 through April 1994 on 2569 breast cancer case subjects and 2588 control subjects, we calculated multivariate odds ratios and population-attributable risks for breast cancer in relation to dietary beta-carotene and vitamin E intake, alcohol consumption, physical activity, and, for postmenopausal women, body mass index. RESULTS: Among all subjects, the following attributable risks for the indicated risk factors were observed: 10.7% (95% confidence interval [CI] = 4.4%-17.0%) for high alcohol intake (i.e., >20 g/day), 15.0% (95% CI = 7.4%-22.9%) for low beta-carotene intake (i.e., <3366 microg/day), 8.6% (95% CI = -0.4%-17.5%) for low vitamin E intake (i.e., <8.5 mg/day), and 11.6% (95% CI = -0.1%-23.3%) for low levels of physical activity. The risks associated with alcohol and beta-carotene intake were larger among premenopausal women, and the risk associated with physical activity was larger among postmenopausal women. Being overweight accounted for 10.2 % (95% CI = 0.2%-20.2%) of breast cancer cases in postmenopausal women. Beta-carotene plus alcohol accounted for 28.1% (95% CI = 16.8-39.4) of the cases. Beta-carotene and physical activity accounted for 32% (95% CI = 14.3-49.8), and these three factors together accounted for 33% (95% CI = 19.9-46.1) of the breast cancer cases in the overall dataset. CONCLUSION: Exposure to a few selected and potentially modifiable risk indicators explained about one third of the cases of breast cancer in this Italian population, indicating the theoretical scope for prevention of the disease.
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Consumo de Bebidas Alcoólicas , Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Exercício Físico , Comportamento Alimentar , Adulto , Idoso , Antioxidantes/administração & dosagem , Estudos de Casos e Controles , Feminino , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Razão de Chances , Pós-Menopausa , Risco , Fatores de Risco , Vitamina E/administração & dosagem , beta Caroteno/administração & dosagemRESUMO
BACKGROUND: The bcl-2 gene (also known as BCL2) encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. The protein has been detected by immunohistochemical procedures in hormonally regulated epithelia. PURPOSE: We analyzed the predictive relevance of Bcl-2 expression on 6-year relapse-free and overall survival in lymph node-negative breast cancers in relation to pathologic (tumor size) and biologic ([3H]thymidine-labeling index, p53 protein expression, and estrogen receptor [ER] status) features. METHODS: The expression of Bcl-2 and p53 was detected by immunohistochemistry on paraffin-embedded sections from 283 node-negative resectable breast cancers treated with local-regional therapy alone until relapse. The [3H]thymidine-labeling index was evaluated on histologic sections after incubation of fresh tumor tissue with [3H]thymidine, and ER content was determined by the dextran-coated charcoal absorption technique. RESULTS: A significantly higher fraction of Bcl-2-positive cells was observed in small, ER-positive, slowly proliferating, and p53-negative tumors than in large, ER-negative, rapidly proliferating, and p53-positive tumors. A stronger association was observed between Bcl-2 and p53 expression than between these variables and [3H]thymidine-labeling index. In univariate analysis, Bcl-2 and p53 expression, [3H]thymidine-labeling index, tumor size, and ER status were indicators for relapse-free and, with the exception of tumor size, overall survival within 6 years of surgery. In multivariate analysis, Bcl-2 failed to maintain its prognostic role for relapse-free and overall survival in the presence of p53 expression, whereas the [3H]thymidine-labeling index was still statistically significant as a predictor for both events. CONCLUSION: The predictive role of Bcl-2 expression on 6-year relapse-free and overall survival was mainly dependent on p53 expression.
Assuntos
Neoplasias da Mama/química , Proteínas Proto-Oncogênicas/análise , Proteína Supressora de Tumor p53/análise , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Valor Preditivo dos Testes , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2 , Receptores de Estrogênio/análise , Estatística como Assunto , Análise de Sobrevida , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Previous epidemiologic studies have suggested that sunscreen use is associated with an increased risk of melanoma skin cancer. Because high nevi (mole) count in adults is a strong predictor of melanoma, we conducted a study examining the number of nevi in 6- to 7-year-old European children, according to their sunscreen use. METHODS: Whole-body and site-specific counts of nevi 2 mm or larger were performed in 631 children in their first year of primary school in four European cities. Independently, parents were interviewed regarding sun exposure, sunscreen use, and physical sun protection of their child. RESULTS: After adjustment for sun exposure and host characteristics (e.g., skin phototype, eye color), the relative risk for high nevus count on the trunk was 1.68 (95% confidence interval [CI] = 1.09-2.59) for the highest level of sunscreen use and 0.59 (95% CI = 0.36-0.97) for the highest level of wearing of clothes while in the sun. The sun protection factor had no effect on nevus counts despite a high median value of 17.4. Sunburn number was not associated with nevus count. The highest risk associated with sunscreen use was found among children who had never experienced sunburn. CONCLUSIONS: In white, European children, sunscreen use appears to be associated with development of nevi, probably because it allows longer sun exposures. Wearing clothes may be an effective way to prevent proliferation of nevi. Since a high nevus count is a strong predictor of melanoma, sunscreen use may be involved in melanoma occurrence because it may encourage recreational sun exposure.
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Nevo/prevenção & controle , Roupa de Proteção , Neoplasias Cutâneas/prevenção & controle , Queimadura Solar/prevenção & controle , Protetores Solares/administração & dosagem , Criança , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Nevo/epidemiologia , Nevo/etiologia , Pais , Roupa de Proteção/estatística & dados numéricos , Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Queimadura Solar/complicações , Queimadura Solar/epidemiologiaRESUMO
AIM: Transbronchial needle aspiration (TBNA) is particularly indicated in diagnosing mediastinal masses or lymphoadenopathy proximal to the airways. Nowadays TBNA has not been widely accepted among pulmonologist and thoracic surgeons. Since its correct management could reduce patient morbidity we adopted this method. Here is presented an overview of our experience over a 18-months training period. METHODS: Fifty patients underwent TBNA. They presented non diagnosed paratracheal or peribronchial lymphadenopathy or masses of >1 cm. TBNA has been considered in order to spare patients the need for more invasive diagnostic procedures. TBNA has been performed with flexible bronchoscope and 19-gauge or 21-gauge needle. RESULTS: We made diagnosis of disease in 25 of 41 patients whose adequate sampling was obtained. 16 cases showed absence of disease despite criteria for adequacy have been confirmed, 9 cases presented an inadequate specimen. The overall diagnostic yield and sensitivity were 50% and 86%. The overall accuracy was 76%. Considering the last 6 months of the training period diagnostic yield increased from 18.7% to 88.2% (P<0.001),accuracy from 56.2% to 88.2% (P=0.04) and frequency of inadequacy decreased from 43.7% to 11.7% (P=0.046). CONCLUSIONS: TBNA resulted a successful diagnostic tool in selected cases as it is safe and permits to spare patients the need for more invasive procedures. These data revealed that experience is mandatory in order to achieve acceptable RESULTS: We think that an experienced operator should require a training period of approximately 50 procedures to obtain a good technique proficiency.
Assuntos
Biópsia por Agulha , Broncoscopia/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Pulmão/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha/instrumentação , Biópsia por Agulha/métodos , Interpretação Estatística de Dados , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Doenças Linfáticas/diagnóstico , Doenças Linfáticas/patologia , Masculino , Pessoa de Meia-Idade , Agulhas , Estadiamento de Neoplasias , Radiografia Torácica , Segurança , Sensibilidade e Especificidade , Cirurgia Torácica , Tomografia Computadorizada por Raios XRESUMO
PURPOSE AND METHODS: We evaluated, in 1,800 patients with node-negative tumors treated with locoregional therapy until relapse, the competitive risks for different types of metastasis by cell proliferation (3H-thymidine labeling index [3H-dT LI]), estrogen receptors (ERs), and progesterone receptors (PgRs), and by the integration of biologic and clinicopathologic information. RESULTS: Hormone receptor status and proliferative activity of the primary tumor were not indicative of contralateral failures. Hormone receptors failed to predict the 8-year incidence of locoregional recurrence, but they were significant indicators of distant metastasis and overall survival. The latter finding was confirmed even in multivariate analysis. Conversely, cell proliferation predicted both locoregional and distant metastases and survival, regardless of patient age, tumor size, and ER and PgR status. Recursive partitioning and amalgamation analysis ascribed to cell proliferation an important prognostic role for locoregional recurrence together with patient age and tumor size. CONCLUSION: Biologic markers, in particular cell proliferation, provide information for the different types of relapse and could complement the predictive role of pathologic staging.
Assuntos
Neoplasias da Mama/patologia , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Divisão Celular , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Análise de Regressão , Fatores de Risco , Taxa de SobrevidaRESUMO
The objective of this study was to compare the use of molecular hybridization by hybrid capture methodology for human papillomavirus (HPV) with the use of demographic and lifestyle variables as intermediate triage in patients with cytological mild dyskaryosis. The study was designed as a prospective study using regression tree analysis of demographic data in consecutive patients who were subjected to colposcopic evaluation at the colposcopy clinic at the First Department of Obstetrics and Gynaecology, University of Milan (Milan, Italy). A total of 177 women were subjected to colposcopy because of a single routine Pap smear showing mild dyskaryosis. A structured interview, sampling for HPV testing for the detection of viral DNA by hybrid capture methodology, and colposcopic evaluation with cervical biopsies were performed for each subject. The accuracies of molecular hybridization for HPV and of the classification model based on the demographic and lifestyle variables in predicting patients with histologically high-grade cervical intraepithelial lesions were measured. The classification model based on the demographic and lifestyle variables showed comparable results with molecular hybridization for HPV (specificity, 0.75 versus 0.73; sensitivity, 0.61 versus 0.67, respectively). The use of demographic and lifestyle variables appears to be a simple and economic possibility for triaging patients with mild dyskaryotic smears in a screening program.
Assuntos
Sondas de DNA de HPV , Papillomaviridae , Infecções por Papillomavirus/patologia , Lesões Pré-Cancerosas/patologia , Infecções Tumorais por Vírus/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Colo do Útero/patologia , Feminino , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Teste de Papanicolaou , Infecções por Papillomavirus/etiologia , Lesões Pré-Cancerosas/etiologia , Prognóstico , Fatores de Risco , Fumar/efeitos adversos , Fumar/patologia , Infecções Tumorais por Vírus/etiologia , Displasia do Colo do Útero/etiologia , Neoplasias do Colo do Útero/etiologia , Esfregaço VaginalRESUMO
The benzo(a)pyrene (BaP) metabolite benzo(a)pyrenediolepoxide (BPDE) is strongly implicated as a causative agent of lung cancer. To assess the risk of exposure to BaP, we made a combined analysis of levels of BPDE adducts to hemoglobin (Hb), serum albumin (SA), and lymphocyte DNA in 44 patients with incident lung cancer, as a prototype of a population mainly exposed to tobacco-derived BaP. We also investigated whether genetic polymorphisms of cytochrome P450IA1 (CYPIA1), microsomal epoxide hydrolase (mEH), and glutathione S-transferase M1 (GSTM1), which are involved in BaP metabolism, can be determinants of adduct formation. BPDE-Hb, BPDE-SA, and BPDE-DNA adducts were quantified as BaP tetrols released from hydrolysis of macromolecules and measured by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry to achieve high specificity and sensitivity. Individuals with detectable Hb adducts were positive for SA adducts but not vice versa, suggesting that BPDE-Hb adducts are less informative indicators of BaP exposure. Using PCR methods on DNA, we characterized GSTM1 deletion, CYPIA1 MspI and exon 7 valine variants, and mEH polymorphisms at amino acid positions 113 (EH3) and 139 (EH4). Levels of BPDE adducts were no different among CYPIA1, mEH, and GSTM1 genotypes. However, individuals with measurable BPDE-SA adducts were CYPIA1 variant carriers more frequently (P = 0.03). There was a slightly higher percentage of DNA detectable adducts in subjects with CYPIA1 exon 7 valine polymorphism. When subjects were classified by both polymorphisms on the mEH gene, those with two slow alleles (EH3 homozygous mutated) and no fast alleles (EH4 homozygous wild type) had a lower frequency of BPDE-SA adducts and no DNA adducts (P = 0.06). These results are based on a small number of observations thus far, but this exploratory study suggests that CYPIA1 and mEH variants might have an impact on BPDE exposure markers such as BPDE-SA adducts. Chemical specificity in adduct measurements is important to identify the biomarkers that reflect BaP exposure more accurately.
Assuntos
Benzopirenos/metabolismo , Proteínas Sanguíneas/metabolismo , DNA de Neoplasias/genética , Epóxido Hidrolases/genética , Glutationa Transferase/genética , Neoplasias Pulmonares/genética , Idoso , Sequência de Bases , Biomarcadores Tumorais/análise , Proteínas Sanguíneas/genética , Sistema Enzimático do Citocromo P-450/metabolismo , DNA de Neoplasias/análise , Epóxido Hidrolases/análise , Genótipo , Glutationa Transferase/sangue , Humanos , Neoplasias Pulmonares/enzimologia , Masculino , Microssomos Hepáticos/enzimologia , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo Genético , Sensibilidade e EspecificidadeRESUMO
1. Cysteinyl-leukotrienes (cysteinyl-LTs) are important mediators in the pathogenesis of asthma. They cause bronchoconstriction, mucus hypersecretion, increase in microvascular permeability, plasma extravasation and eosinophil recruitment. 2. We investigated the pharmacological profile of the cysteinyl-LT antagonists CGP 45715A (iralukast), a structural analogue of LTD4 and CGP 57698, a quinoline type antagonist, in human airways in vitro, by performing binding studies on human lung parenchyma membranes and functional studies on human isolated bronchial strips. 3. Competition curves vs [3H]-LTD4 on human lung parenchyma membranes demonstrated that: (a) both antagonists were able to compete for the two sites labelled by [3H]-LTD4; (b) as in all the G-protein coupled receptors, iralukast and CGP 57698 did not discriminate between the high and the low affinity states of the CysLT receptor labelled by LTD4 (Ki1=Ki2= 16.6 nM+/-36% CV and Ki1= Ki2 = 5.7 nM+/-19% CV, respectively); (c) iralukast, but not CGP 57698, displayed a slow binding kinetic, because preincubation (15 min) increased its antagonist potency. 4. In functional studies: (a) iralukast and CGP 57698 antagonized LTD4-induced contraction of human bronchi, with pA2 values of 7.77+/-4.3% CV and 8.51+/-1.6% CV, respectively, and slopes not significantly different from unity; (b) the maximal LTD4 response in the presence of CGP 57698 was actually increased, thus clearly deviating from apparent simple competition. 5. Both antagonists significantly inhibited antigen-induced contraction of human isolated bronchial strips in a concentration-dependent manner, lowering the upper plateau of the anti-IgE curves. 6. In conclusion, the results of the present in vitro investigation indicate that iralukast and CGP 57698 are potent antagonists of LTD4 in human airways, with affinities in the nanomolar range, similar to those obtained for ICI 204,219 and ONO 1078, two of the most clinically advanced CysLT receptor antagonists. Thus, these compounds might be useful drugs for the therapy of asthma and other allergic diseases.
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Benzopiranos/farmacologia , Brônquios/efeitos dos fármacos , Leucotrieno D4/antagonistas & inibidores , Pulmão/efeitos dos fármacos , Antígenos/imunologia , Benzopiranos/metabolismo , Ligação Competitiva , Brônquios/metabolismo , Brônquios/fisiologia , Humanos , Técnicas In Vitro , Leucotrieno D4/metabolismo , Pulmão/metabolismo , Contração Muscular/efeitos dos fármacos , Contração Muscular/imunologiaRESUMO
We have identified and characterized two different subclasses of binding site for the novel peptido-leukotriene (LT) antagonist, [3H]ICI 198,615, in membranes from human lung parenchyma using a receptor-ligand assay. This novel compound is representative of a new class of LT receptor antagonists and it has been demonstrated to be several orders of magnitude more potent and selective than most other LT antagonists described to date. The binding of [3H]ICI 198,615 is rapid, specific and saturable. Equilibrium was reached within 5-10 min. Non linear fitting of dissociation time courses has revealed the presence of two different components (K(off)1 = 8.3 +/- 6.8 x 10(-4) sec-1 and K(off)2 = 0.79 +/- 1.66 x 10(-3) sec-1) of the kinetic curves, suggesting heterogeneity of the binding sites. Computer analysis of equilibrium binding data obtained at 25 degrees results in a model with two classes of binding sites, a high affinity-low capacity class with Kd1 = 0.024 +/- 0.014 nM and Bmax1 = 0.015 +/- 0.004 pmol/mg protein and a low affinity-high capacity class with Kd2 = 6326 +/- 3859 nM and Bmax2 = 473 +/- 383 pmol/mg protein. In competition studies, LTD4 was also found to interact with two classes of binding site (Kd1 = 0.016 +/- 0.008 nM and Kd2 = 15195 +/- 8965 nM). On the contrary, LTE4 and LTC4 were found to interact with a homogeneous class of sites only with Kd = 7466 +/- 4629 nM and Kd = 428 +/- 73 nM, respectively. Furthermore, we have evaluated the effect of a number of LT antagonists on the binding of [3H]ICI 198,615. Ro 24-5913 (Kd = 3.0 +/- 2.1 nM), FPL55712 (Kd = 4945 +/- 2868 nM), LY171883 (Kd = 19628 +/- 12365 nM), SKF 104353 (Kd = 74.2 +/- 46 nM) and its enantiomer SKF 104373 (Kd = 13627 +/- 6813 nM) were found to interact with a single class of binding sites. The present studies indicate a heterogeneity of binding sites for ICI 198,615 in membranes from human lung parenchyma and that ICI 198,615 is a very potent and selective antagonist of LTD4 receptors in this tissue.
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Indazóis/metabolismo , Pulmão/metabolismo , SRS-A/metabolismo , Asma/tratamento farmacológico , Asma/metabolismo , Sítios de Ligação , Cromonas/farmacologia , Ácidos Dicarboxílicos/farmacologia , Humanos , Indazóis/antagonistas & inibidores , Indazóis/farmacologia , Cinética , Receptores Imunológicos/efeitos dos fármacos , Receptores de Leucotrienos , SRS-A/antagonistas & inibidores , Software , Tiazóis/farmacologiaRESUMO
In vitro passive sensitization of human lung parenchyma with hyper-immune serum did not affect the release of prostaglandin D2 (PGD2) or leukotriene (LT)-like activity upon challenge with anti-IgE antibody with respect to control lung, despite a marked difference in IgE levels between control (C) and sensitized (S) tissue. Binding studies with [3H]LTC4, [3H]LTD4 and [3H]mepyramine (a histamine H1 antagonist) showed a statistically significant increase in the amount bound in sensitized vs control lung for [3H]mepyramine only. Contractile response to 5 x 10(-5) M histamine (H) in C and S lung parenchymal strips did not correlate with binding data. It is concluded that in vitro elevated IgE levels do not affect the interaction of sulfidopeptide leukotrienes with their putative receptors. As for the observed increase in [3H]mepyramine binding, this might not represent a true increase in histamine receptors on lung smooth muscle cells.
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Eicosanoides/metabolismo , Pulmão/metabolismo , Pirilamina/metabolismo , SRS-A/metabolismo , Animais , Cobaias , Histamina/farmacologia , Humanos , Imunização Passiva , Imunoglobulina E/farmacologia , Técnicas In Vitro , Pulmão/imunologia , Músculo Liso/efeitos dos fármacos , Prostaglandina D2/análise , Receptores Histamínicos H1/metabolismoRESUMO
p53 expression detected by immunocytochemistry is emerging as a novel potentially useful prognostic indicator in breast carcinoma. However, additional research is warranted because a consensus has not yet been achieved on: i) methodology and quality control issues; ii) its association with other new biological prognostic indicators; iii) its prognostic value in multivariate analysis including conventional and new pathobiological features and; iv) its clinical usefulness either as a prognostic and predictive factor. This study was undertaken in a series of 165 early-stage breast cancer patients (median follow-up of 5 years) to compare the prognostic role of p53 expression with that of several other markers that have been found to be of value, using a multivariate statistical analysis. These factors are: tumour angiogenesis, epidermal growth factor receptor (EGFR), c-erbB-2 expression, cathepsin D, growth fraction by Ki-67 antibody, DNA ploidy and S-phase fraction. The main results observed were: i) 47 of 165 (28.5%) carcinomas had pAb 1801 staining and were considered as p53-positive; ii) p53 expression was weakly associated with S-phase fraction by flow cytometry (OR=1.86; p=0.085); iii) p53 expression was significantly associated with recurrence (p53 negative [-] versus weak positive [+] tumours: p=0.07 and odds ratio of 2.21; p53 negative [-] versus high positive [++] tumours: p=0.01 and odds ratio of 2.86) and death (p53-versus +: p=0.53 and odds ratio of 1.35; p53- versus ++: p=0.05 and odds ratio of 2.53); iv) the determination of p53 is able to identify a subset of high risk patients in c-erbB-2 negative tumours, this group being generally considered at good prognosis; v) In multivariate analysis on relapse-free survival including all the above markers only tumour angiogenesis, cathepsin D, EGFR and S-phase fraction and nodal status retained significance, and for overall survival only tumour angiogenesis was significant and independent. This new information on p53 expression could be useful to the clinician for a more rationale approach in defining prognosis of breast cancer patients. The prognostic value of p53 depends on which other markers are additionally analyzed and previous studies have not always assayed tumour angiogenesis, which is the most important factor in this series. p53 still need to be assessed as a potential predictor of response to chemo or radiotherapy, because of its role in monitoring DNA damage.
RESUMO
Sixty-two schizophrenic patients and 26 healthy volunteers were administered the Wisconsin Card Sorting Test (WCST) a task putatively specific for frontal functions and the Wechsler Adult Intelligence Scale (WAIS). The purpose of this study was to evaluate the presence of specific frontal lobe deficits in the course of schizophrenia and the capacity of these tasks to discriminate between patients and controls. Schizophrenic patients showed a poorer performance than control subjects in both tests. No evidence emerged to support a higher discriminant power for the WCST in identifying schizophrenic subjects from healthy controls compared with the WAIS. Our data suggest that the deficit in WCST performance is not selective, but rather part of a more generalized neuropsychological impairment in schizophrenic patients.
Assuntos
Transtornos Neurocognitivos/diagnóstico , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Transtornos Neurocognitivos/fisiopatologia , Transtornos Neurocognitivos/psicologia , Psicometria , Valores de Referência , Esquizofrenia/fisiopatologia , Escalas de Wechsler/estatística & dados numéricosRESUMO
We report the results of a pilot study on predeposit autotransfusion for elective surgery. In 2 years 319 U, each consisting of 350 ml of blood, were donated by 206 patients. Each patient gave 1, 2, or 3 U according to hematocrit levels within 10 days of undergoing surgery on the gastrointestinal tract, lung, liver, kidney, brain, thyroid, arteries, or breast. A hemoglobin drop of about 0.8 gm/dl occurred after each blood donation. A total of 259 autologous and 128 homologous U were transfused to 166 patients during surgery or within postoperative day 4; 40 patients required no blood transfusion. About 70% of patients did not need homologous blood products in addition to autologous units. The most active team of surgeons and anesthesiologists covered about 40% of the patients' blood needs during the study period with autologous units. No patient experienced untoward reactions before, during, or after surgery. Surgeons' and anesthesiologists' responses to the program improved during the study as soon as the advantages of the procedure became clearer. However, gentle pressure from the Transfusion Center was essential for the program's expansion. The patients' acceptance was excellent. We conclude that predeposit autotransfusion is a safe and feasible procedure for transfusion treatment in elective surgery.
Assuntos
Bancos de Sangue/organização & administração , Transfusão de Sangue Autóloga/estatística & dados numéricos , Cirurgia Geral/métodos , Adulto , Idoso , Feminino , Hematócrito , Hemoglobinas/análise , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Período Pós-OperatórioRESUMO
BACKGROUND: In 1986 the authors began a prospective study to investigate operative mortality and long-term survival after surgery of patients in their seventh decade of life suffering from non-small cell lung cancer in Stages I and II. METHODS: From 1986 to 1991, 519 lung cancer patients underwent radical surgery. Of this number, 54 were aged 70 years and older (Group A), while 465 fell within the 40-69 age range (Group B). The most widely applied operation in absolute terms was lobectomy (no difference between the two groups). Pneumonectomies were performed in greater number in Group B (p < .025), whereas minor resections were more numerous in Group A (p < .0005). RESULTS: Operative mortality, i.e., within 30 days of operation, was higher in the elderly patients, but without any significant difference between the two groups (A, 5.5%; B, 1.3%). Morbidity presented a very similar pattern: Group A, 7.4%; Group B, 6.9%. Actuarial survival at 2 and 5 years for the patients in Stage I was distributed as follows: Group A, 78.2% and 52.1%; Group B, 80.0% and 57.8%. CONCLUSIONS: No statistically significant difference exists between the survival rates of the two groups. The data gathered suggest that patients in their seventh decade of life can receive surgical treatment exactly as younger patients in the case of non-small cell lung cancer in Stages I and II.
Assuntos
Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Taxa de SobrevidaRESUMO
The solitary pulmonary nodule often presents a diagnostic challenge to the specialist because the nature of the nodule is often indeterminate at the end of the usual diagnostic process, and operation frequently is required before a definite diagnosis can be made. We have conducted a randomized, prospective trial to evaluate the diagnostic efficacy of video-assisted thoracic surgery versus muscle-sparing lateral thoracotomy. Between January 1991 and May 1994, 44 patients suffering from solitary pulmonary nodule were divided at random into two groups: the nodule was removed in 22 cases by video-assisted thoracic surgery and in 22 cases by lateral thoracotomy. Nineteen wedge resections, 1 segmentectomy, and 2 lobectomies were performed in the first group and 13 wedge resections, 8 segmentectomies, and 1 lobectomy in the second group. An "access" thoracotomy had to be performed in 5 patients in the video-assisted thoracic surgery group. The operating room time was 97.2 +/- 32.9 minutes in the video-assisted thoracic surgery group and 130.5 +/- 14 minutes in the lateral thoracotomy group (p > 0.05). In both groups a final diagnosis was made in 100% of cases. The postoperative hospital stay was 4.6 +/- 1.08 days in the video-assisted thoracic surgery group and 7.8 +/- 0.89 days in the lateral thoracotomy group (p < 0.01). Pain was evaluated on a visual analogue scale; the scores were 26.5 +/- 11.6 in the video-assisted thoracic surgery group and 48.3 +/- 12.8 in the lateral thoracotomy group (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Neoplasias Pulmonares/diagnóstico , Nódulo Pulmonar Solitário/diagnóstico , Televisão , Toracoscopia/métodos , Toracotomia/métodos , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Nódulo Pulmonar Solitário/cirurgiaRESUMO
Pulmonary sequestration is a congenital anomaly of lung parenchyma that can be definitively treated only with surgical resection. We report a case of an intralobar sequestration of the right lower pulmonary lobe in an infant successfully treated with video-thoracoscopic surgical removal of the involved lobe at 6 months of age.
Assuntos
Sequestro Broncopulmonar/cirurgia , Endoscopia , Pneumonectomia , Toracoscopia , Gravação em Vídeo , Sequestro Broncopulmonar/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Grampeadores Cirúrgicos , Toracotomia/métodosRESUMO
BACKGROUND: Atrial fibrillation is a common complication of early postoperative period in lung cancer thoracotomy. Its clinical incidence and short- and long-term impact on overall mortality has never been definitely assessed; moreover, it is unclear whether the arrhythmia represents an independent cardiac risk factor. METHODS: We prospectively studied 233 consecutive patients undergoing operation for lung cancer (170 with non-small-cell lung cancer). Postoperative atrial fibrillation incidence was related to different clinical factors possibly involved in its occurrence and to both short- and long-term survival. RESULTS: Atrial fibrillation occurred in 28 patients (12%) (same percentage in non-small-cell lung cancer); a strong relationship was observed between arrhythmia and age, history of hypertension and associated lymph node resection. The mean hospitalization time was 14 +/- 4 days in patients developing atrial fibrillation and 13 +/- 4 days in those who did not (p = not significant). No difference was observed between the two groups with regard to short- or long-term mortality or to long-term atrial fibrillation recurrences, also when considering the entire population and only non-small-cell lung cancer, separately. CONCLUSIONS: At our institution, early atrial fibrillation occurrence after operation for lung cancer does not show any negative impact on short- and long-term mortality or on recurrence rate.
Assuntos
Fibrilação Atrial/etiologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Fibrilação Atrial/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Complicações Pós-Operatórias/mortalidade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , ToracotomiaRESUMO
BACKGROUND: Traditional nonoperative diagnostic approaches to the solitary pulmonary nodule (bronchoscopy and percutaneous needle biopsy) can be inconclusive. Video-assisted thoracic surgery (VATS) provides a minimally invasive way to diagnose and treat these nodules. We evaluated the use of a dedicated intraoperative ultrasound probe as an aid in localization of small pulmonary nodules during VATS. METHODS: An intraoperative ultrasound examination during a thoracoscopic procedure was performed on 18 patients to localize deep pulmonary nodules less than 20 mm in diameter without a definitive diagnosis by preoperative imaging techniques. RESULTS: In the 18 patients, all nodules were successfully identified by intraoperative ultrasound. A definitive pathologic diagnosis was obtained from thoracoscopic biopsy or resection. The final diagnoses were primary lung cancer in 5 patients, metastatic lesions in 4 patients, hamartoma or chondroma in 4, granuloma in 3, and interstitial fibrosis in 2 patients. CONCLUSIONS: In our experience, intraoperative ultrasound can safely and effectively localize invisible or nonpalpable pulmonary nodules at the time of thoracoscopy. This may help surgeons perform minimally invasive lung resections with clear surgical margins.