RESUMO
Statistics from structural genomics initiatives reveal that around 50-55% of the expressed, non-membrane proteins cannot be purified and therefore structurally characterized due to solubility problems, which emphasized protein solubility as one of the most serious concerns in structural biology projects. Lactobacillus plantarum CECT 748T produces an aggregation-prone glycosidase (LpBgl) that we crystallized previously. However, this result could not be reproduced due to protein instability and therefore further high-resolution structural analyses of LpBgl were impeded. The obtained crystals of LpBgl diffracted up to 2.48Å resolution and permitted to solve the structure of the enzyme. Analysis of the active site revealed a pocket for phosphate-binding with an uncommon architecture, where a phosphate molecule is tightly bound suggesting the recognition of 6-phosphoryl sugars. In agreement with this observation, we showed that LpBgl exhibited 6-phospho-ß-glucosidase activity. Combination of structural and mass spectrometry results revealed the formation of dimethyl arsenic adducts on the solvent exposed cysteine residues Cys211 and Cys292. Remarkably, the double mutant Cys211Ser/Cys292Ser resulted stable in solution at high concentrations indicating that the marginal solubility of LpBgl can be ascribed specifically to these two cysteine residues. The 2.30Å crystal structure of this double mutant showed no disorder around the newly incorporated serine residues and also loop rearrangements within the phosphate-binding site. Notably, LpBgl could be prepared at high yield by proteolytic digestion of the fusion protein LSLt-LpBgl, which raises important questions about potential hysteretic processes upon its initial production as an enzyme fused to a solubility enhancer.
Assuntos
Glicosídeo Hidrolases/química , Lactobacillus plantarum/química , Soluções/química , Domínio Catalítico , Cisteína/química , Cisteína/metabolismo , Glucosidases/química , Glucosidases/metabolismo , Glicosídeo Hidrolases/metabolismo , Lactobacillus plantarum/metabolismo , Fosfatos/química , Fosfatos/metabolismo , Proteólise , Serina/química , Serina/metabolismo , Solubilidade , Especificidade por SubstratoRESUMO
Conventional wastewater treatment plants (WWTPs) are designed to remove mainly the organic matter, nitrogen and phosphorus compounds and suspended solids from wastewater but are not capable of removing chemicals of human origin, such as pharmaceutical and personal care products (PPCPs). The presence of PPCPs in wastewater has environmental effects on the water bodies receiving the WWTP effluents and renders the effluent as unsuitable as a nonconventional water source. Considering PPCPs as non-desirable outputs, the shadow prices methodology has been implemented using the output distance function to measure the environmental benefits of removing five PPCPs (acetaminophen, ibuprofen, naproxen, carbamazepine and trimethoprim) from WWTP effluents discharged to three different ecosystems (wetland, river and sea). Acetaminophen and ibuprofen show the highest shadow prices of the sample for wetland areas. Their values are 128.2 and 11.0 /mg respectively. These results represent a proxy in monetary terms of the environmental benefit achieved from avoiding the discharge of these PPCPs in wetlands. These results suggest which PPCPs are urgent to remove from wastewater and which ecosystems are most vulnerable to their presence. The findings of this study will be useful for the plant managers in order to make decisions about prioritization in the removal of different pollutants.
Assuntos
Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água , Monitoramento Ambiental , Humanos , Preparações Farmacêuticas , RiosRESUMO
Efficient management of Waste Water Treatment Plants (WWTPs) can produce significant environmental and economic benefits. Energy benchmarking can be used to compare WWTPs, identify targets and use these to improve their performance. Different authors have performed benchmark analysis on monthly or yearly basis but their approaches suffer from a time lag between an event, its detection, interpretation and potential actions. The availability of on-line measurement data on many WWTPs should theoretically enable the decrease of the management response time by daily benchmarking. Unfortunately this approach is often impossible because of limited data availability. This paper proposes a methodology to perform a daily benchmark analysis under database limitations. The methodology has been applied to the Energy Online System (EOS) developed in the framework of the project "INNERS" (INNovative Energy Recovery Strategies in the urban water cycle). EOS calculates a set of Key Performance Indicators (KPIs) for the evaluation of energy and process performances. In EOS, the energy KPIs take in consideration the pollutant load in order to enable the comparison between different plants. For example, EOS does not analyse the energy consumption but the energy consumption on pollutant load. This approach enables the comparison of performances for plants with different loads or for a single plant under different load conditions. The energy consumption is measured by on-line sensors, while the pollutant load is measured in the laboratory approximately every 14 days. Consequently, the unavailability of the water quality parameters is the limiting factor in calculating energy KPIs. In this paper, in order to overcome this limitation, the authors have developed a methodology to estimate the required parameters and manage the uncertainty in the estimation. By coupling the parameter estimation with an interval based benchmark approach, the authors propose an effective, fast and reproducible way to manage infrequent inlet measurements. Its use enables benchmarking on a daily basis and prepares the ground for further investigation.
Assuntos
Benchmarking , Análise da Demanda Biológica de Oxigênio , Conservação dos Recursos Naturais , Eliminação de Resíduos Líquidos , Algoritmos , Lógica Fuzzy , Aprendizado de Máquina , Redes Neurais de Computação , Análise de Regressão , Temperatura , IncertezaRESUMO
The effects of the lipopolysaccharide (LPS) from Ochrobactrum intermedium was evaluated in sheep experimentally infected with Fasciola hepatica. Animals were divided into four groups: two treated with the LPS (T1/T2) and two controls (C1/C2). T1/C1 were slaughtered at 30 days postinfection (dpi) and T2/C2 at 85 dpi. Body weight and body condition were found higher in T1 and T2 than in controls, although differences were not significant. Treated sheep showed lower cumulative fecal egg count than controls (p < 0.01). Levels of red blood cells (RBC), white blood cells, hemoglobin, and hematocrit (HCT) were higher in T1 and T2. Significant differences (p < 0.05) in RBC and HCT were found between groups at 84 dpi. More severe macrocytic and hypochromic anemia was observed in C1 and C2 than in treated groups. Total protein and albumin values were higher in T1 and T2 (p < 0.01) until 29 dpi. At the end of the trial, no significant differences were observed in hepatic enzymes, although gamma-glutamyl transferase and aspartate aminotransferase values were higher in C2, and alanine aminotransferase was higher in T2. At necropsy, the mean weight of liver, fibrosis in portal triads, and ganglion size were similar in all groups. The number and size of flukes was greater in C2 than in T2 (p < 0.05). The histological examinations revealed a higher degree of parenchymatous fibrosis in T2 compared to C2 (p < 0.05). The administration of LPS from O. intermedium increased the nonspecific resistance against F. hepatica in experimentally infected sheep.
Assuntos
Fasciola hepatica/imunologia , Fasciolíase/veterinária , Fatores Imunológicos/farmacologia , Lipopolissacarídeos/farmacologia , Ochrobactrum , Doenças dos Ovinos/parasitologia , Animais , Fasciolíase/tratamento farmacológico , Fasciolíase/parasitologia , Imunomodulação/imunologia , Ovinos , Doenças dos Ovinos/tratamento farmacológicoRESUMO
Economic feasibility assessments represent a key issue for selecting which wastewater treatment processes should be implemented. The few applications that exist focus on the positive economic value of externalities, overlooking the existence of negative externalities. However, wastewater treatment plants (WWTPs) consume a significant amount of energy, contributing to climate change. In this context, as a pioneering approach, greenhouse gas emissions (GHG) have been incorporated as a negative externality of wastewater treatment. Within this framework, this study aims to compare the economic feasibility of five technologies, both intensive and extensive, for small communities. The results show that both the investment and operation costs are higher for intensive than for extensive technologies. Moreover, significant differences in the value of negative externalities were observed. This study demonstrates that from an economic perspective, constructed wetland is the most suitable option for treating wastewater in small agglomerations.
Assuntos
Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/análise , Monitoramento Ambiental , Efeito EstufaRESUMO
The purpose of this study was to identify molecular markers associated with tumor recurrence and survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). We studied the expression profile of 63 pre-treatment tumor biopsies obtained from locally advanced HNSCCs treated with standard treatments. Cluster analysis identified three tumor subtypes associated with significant differences in local recurrence-free survival (LRFS) (P<0.001), progression free-survival (PFS) (P<0.009) and overall survival (OS) (P<0.004). Tumor subtype 1, associated with short LRFS, PFS and OS, showed features of epithelial-mesenchymal transition and undifferentiation. It also overexpressed genes involved in cell adhesion, NF-κB and integrin signalling. Tumor subtype 3, associated with longer LRFS, PFS and OS, showed a high degree of differentiation and overexpressed genes located in chromosomal regions 19q13 and 1q21. Tumor subtype 2, which had an intermediate clinical outcome between subtype 1 and subtype 3, overexpressed genes involved in branching morphogenesis. Finally, we validated the association between gene cluster classification and patient survival using Gene Set Enrichment Analysis and two HNSCC data sets obtained from two independent patient cohorts. In conclusion, we generated a gene prognostic signature associated with survival in locally advanced patients using the expression profile of the pre-treatment tumor biopsy. Independent prospective studies would be necessary to assess if the proposed survival signature could help to guide clinical management of HNSCC.
Assuntos
Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Análise por Conglomerados , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Prognóstico , Modelos de Riscos Proporcionais , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Efficiency and productivity are important measures for identifying best practice in businesses and optimising resource-use. This study analyses how these two measures change across the period 2003-2008 for 196 wastewater treatment plants (WWTPs) in Spain, by using the benchmarking methods of Data Envelopment Analysis and the Malmquist Productivity Index. To identify which variables contribute to the sustainability of the WWTPs, differences in efficiency scores and productivity indices for external factors are also investigated. Our results indicate that both efficiency and productivity decreased over the five years. We verify that the productivity drop is primarily explained by technical change. Furthermore, certain external variables affected WWTP efficiency, including plant size, treatment technology and energy consumption. However, plants with low energy consumption are the only ones which improve their productivity. Finally, the benchmarking analyses proved to be useful as management tools in the wastewater sector, by providing vital information for improving the sustainability of plants.
Assuntos
Eficiência Organizacional , Eficiência , Modelos Teóricos , Eliminação de Resíduos Líquidos , Benchmarking , Pegada de Carbono , EspanhaRESUMO
Water reuse is an emerging and promising non-conventional water resource. Feasibility studies are essential tools in the decision making process for the implementation of water-reuse projects. However, the methods used to assess economic feasibility tend to focus on internal costs, while external impacts are relegated to unsubstantiated statements about the advantages of water reuse. Using the concept of shadow prices for undesirable outputs of water reclamation, the current study developed a theoretical methodology to assess internal and external economic impacts. The proposed methodological approach is applied to 13 wastewater treatment plants in the Valencia region of Spain that reuse effluent for environmental purposes. Internal benefit analyses indicated that only a proportion of projects were economically viable, while when external benefits are incorporated all projects were economically viable. In conclusion, the economic feasibility assessments of water-reuse projects should quantitatively evaluate economic, environmental and resource availability.
Assuntos
Conservação dos Recursos Naturais/economia , Meio Ambiente , Reciclagem/economia , Purificação da Água/economia , Análise Custo-Benefício , EspanhaRESUMO
INTRODUCTION. Esthesioneuroblastoma (ENB) is a very uncommon malignant tumor with a neuroectodermal origin that usually involves the anterior cranial fossa and nasal cavity. OBJECTIVES. To review our experience in the management of ENB and assess the validity of the histopathological diagnosis, modality of treatment and prognostic factors of the disease comparing our findings with the literature. METHODS. A retrospective study of 11 cases with the diagnosis of esthesioneuroblastoma treated in our hospital between 2000 and 2008. Statistical analysis was performed in search for prognostic factors. The bibliography about ENB published between 1990 and 2009 was reviewed RESULTS. There were 3 women and 8 men, with a mean age of 42 years old (range 20-71y). Their symptoms upon admission were nasal obstruction (81%), epistaxis (27%), visual loss (18%), headache and others. According to the Kadish Stage, 2 were stage B and 9 were stage C. Dulguerov and Calcaterra Classification was also used: 2 were T2, 3 were T3 and 6 were T4. The hystopathological result according to the Hyams classification was: 2 cases in stage I, 4 in stage II, 3 in stage III and 2 in stage IV. The two cases classified in stage IV changed the diagnosis to undifferenciate tumor in the second biopsy. A subcranial approach was performed in 8 cases combined with endonasal endoscopy to confirm the total removal, followed by radiotherapy in all and chemotherapy in one case, resulting on 62% (5 patients) being alive without disease, 12,5% (1 p) alive with disease, and 25% (2 p) dead of disease. Another patient was operated by a single endonasal endoscopic approach and a subtotal removal was achieved. This patient is alive without disease. The other 2 patients were treated by biopsy plus radiotherapy and chemotherapy, because they were considered unresectable, and one of them is alive with disease and the other one is dead of disease. Radiotherapy was performed in all cases and chemotherapy in 5 cases. The hystopathological grading system of Hyams was considered statistically significant as a prognostic factor of disease-free survival. CONCLUSIONS. When the hystopathological diagnosis of ENB is considered, the Hyams classification can be valid considering grade IV as an advanced stage that is sometimes difficult to differentiate from other undiferentiated tumors. The subcranial approach or craneofacial resection in advanced stages (Kadish C and some B) should be considered as the first treatment of choice. Radiotherapy is indicated in all cases and chemotherapy in selected cases. Hyams' classification was the only staging system that proved useful as a prognostic factor in our series.
Assuntos
Estesioneuroblastoma Olfatório/patologia , Estesioneuroblastoma Olfatório/terapia , Cavidade Nasal/patologia , Neoplasias Nasais/patologia , Neoplasias Nasais/terapia , Adulto , Idoso , Fossa Craniana Anterior/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Base do Crânio/patologia , Neoplasias da Base do Crânio/terapia , Espanha , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: We carried out a phase I clinical trial to establish the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of the combination of liposome-encapsulated doxorubicin citrate (LD) and docetaxel in breast cancer patients. PATIENTS AND METHODS: Patients with HER-2-overexpressing stages II and IIIA breast cancers were treated in different dose cohorts of three patients. The MTD cohort was expanded up to six patients. The patients received LD and docetaxel every 21 days, plus weekly trastuzumab, with pegfilgrastim support. RESULTS: A total of 20 patients were enrolled, 18 of them being assessable for toxicity and response. DLTs observed for this combination were diarrhea, fatigue, febrile neutropenia, stomatitis, myalgia, and nonneutropenic infection (pneumonia). LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21 days have been the MTD, with no episode of DLT observed. Seven patients developed left ventricular ejection fraction decline (six grade 1 and one grade 2). No interruptions of the treatment were needed as a consequence of cardiac toxicity. Pathologic complete response was achieved in eight patients (44%). CONCLUSIONS: The MTD and recommended dose for phase II trials of LD and docetaxel are 50 and 60 mg/m(2), respectively. The achieved results on cardiotoxicity are promising.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Genes erbB-2 , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/genética , Estudos de Coortes , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Humanos , Lipossomos , Pessoa de Meia-Idade , Taxoides/administração & dosagem , TrastuzumabRESUMO
Cryopreserved human tendons were sutured with different variations of a modified Kessler-type grasping suture in a series of different designs in order to assess the influence of the distance between the cross-stitch on the core suture (5 and 10â¯mm from the cut tendon edge) on the peripheral suture. An original mathematical model was employed to explain the mechanical behavior (strength, deformation, and distribution of load) of the different suture designs. The effect of the peripheral epitendinous suture, combined with the distance of the core suture, was evaluated. The variation of core suture distance had no relevant consequences on the overall resilience of the design. However, increasing the distance between the cross-stitches of the core suture reduces the deformation that is absorbed not only by the core suture itself but also by the peripheral suture. Adding a peripheral epitendinous suture to a 10-mm design almost doubles the breaking load in absolute values. The mathematical model predicts that the peripheral suture will support a greater load when the distance of the core suture cross-stitches is increased. The evidence level is II.
Assuntos
Procedimentos Ortopédicos/métodos , Técnicas de Sutura , Suturas , Traumatismos dos Tendões/cirurgia , Tendões/cirurgia , Fenômenos Biomecânicos/fisiologia , Humanos , Procedimentos de Cirurgia Plástica/métodos , Resistência à Tração/fisiologiaRESUMO
BACKGROUND: To quantify the morphological changes in the surface of the back of adolescents with idiopathic scoliosis as a result of treatment with braces and to correlate them with radiographic changes. MATERIAL AND METHODS: An analytical, cohort, prospective study on a sample of 31 adolescents with idiopathic scoliosis. We divided them into two groups: eleven treated with braces and twenty without them. Quantification of the deformity was performed on two separate occasions with an interval of one year using three systems: 1) angle of trunk rotation (scoliometer); 2) surface topography; 3) full spine X-rays. RESULTS: No statistically significant differences were detected between the initial and final assessment of the topographic and radiographic variables in the group with braces. In the untreated group, only in measures with the scoliometer significant differences were registered. A positive correlation was found between the Cobb angle difference of the main curve with two topographic variables that quantify the asymmetry in the axial and coronal plane, respectively. DISCUSSION: In following patients with scoliosis treated with braces, we should consider and evaluate not only radiographic parameters such as the Cobb angle, but also clinical and topographic parameters that quantify the external deformity of the back, as there is a clinical-radiographic discrepancy amply demonstrated in the literature. The improvement of the external shape of the back is a very important factor for the patient, and can influence a better completion of the orthopedic treatment. In our study, the scoliotic curve and external deformity of the back remained stable during the follow-up period in both treated and untreated patients.
ANTECEDENTES: Cuantificar los cambios morfológicos producidos en la superficie de la espalda de adolescentes con escoliosis idiopática como resultado del tratamiento mediante corsé y correlacionarlos con las variaciones radiográficas. MATERIAL Y MÉTODOS: Estudio analítico, de cohortes, prospectivo, sobre una muestra de 31 adolescentes con escoliosis idiopática divididos en dos grupos: 11 con tratamiento mediante corsé y 20 sin corsé. Se realizó una cuantificación de la deformidad en dos ocasiones separadas entre sí por un intervalo de un año mediante tres sistemas: 1) ángulo de rotación del tronco (escoliómetro); 2) topografía de superficie; 3) radiografía simple de raquis completo. RESULTADOS: No se detectaron diferencias estadísticamente significativas entre la valoración inicial y final de las variables topográficas y radiográficas en el grupo con corsé. En el grupo no tratado, sólo hubo diferencias significativas para las medidas del escoliómetro. Se encontró una correlación positiva entre la diferencia del ángulo de Cobb de la curva principal con la de dos variables topográficas que cuantifican la asimetría en el plano axial y en el coronal, respectivamente. DISCUSIÓN: En el seguimiento de pacientes con escoliosis tratados con corsé, se deben tener en cuenta y valorar no sólo parámetros radiográficos como el ángulo de Cobb, sino también parámetros clínicos y topográficos que cuantifiquen la deformidad externa de la espalda, ya que existe una discrepancia clínico-radiográfica demostrada de manera amplia en la literatura. La mejoría de la forma externa de la espalda es un factor muy importante para el paciente y es lo que va a percibir fundamentalmente, lo que puede influir en una mejor cumplimentación del tratamiento ortopédico. En nuestro estudio, la curva escoliótica, así como la deformidad externa de la espalda, se mantuvo estable en el período de seguimiento tanto en los pacientes tratados con corsé como en los no tratados.
Assuntos
Dorso , Escoliose , Adolescente , Dorso/anatomia & histologia , Estudos de Coortes , Humanos , Estudos Prospectivos , Radiografia , Escoliose/complicaçõesRESUMO
BACKGROUND: The tuberculin skin test (TST) is the most commonly used tool to detect infection with Mycobacterium tuberculosis. We sought to determine whether tuberculin skin testing is useful to detect latent infection by M. tuberculosis in a population that was vaccinated with the Bacille Calmette Guérin (BCG) vaccine. METHODS: We performed a cross-sectional study during October 2000-February 2001, enrolling first and sixth graders from a random, stratified sample of public elementary schools in Orizaba, Veracruz, Mexico. We assessed the relationship between sociodemographic and epidemiological information, BCG scars, and TST reactivity. RESULTS: There were 858 children enrolled in the study with a completed questionnaire and TST result. The prevalence of a positive TST result (> or =10 mm) was 12.4%. Controlling for BCG scar, age, and other characteristics, close contact with pulmonary tuberculosis patients (odds ratio 6.56, 95% confidence interval 2.05-21.07, P = 0.001) was independently associated with TST reactivity. CONCLUSIONS: TST results helped identify children in a BCG-vaccinated population who had recent exposure to persons with pulmonary tuberculosis, were probably infected with M. tuberculosis, and could benefit from treatment for their latent tuberculosis infection.
Assuntos
Vacinas Bacterianas/uso terapêutico , Mycobacterium bovis/imunologia , Teste Tuberculínico/métodos , Tuberculose Pulmonar/diagnóstico , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Estudos Transversais , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , México/epidemiologia , Mycobacterium tuberculosis/imunologia , Prevalência , Fatores de Risco , Distribuição por Sexo , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/imunologiaRESUMO
Orthotopic transplantation of human tumors in nude mice reproduces the pattern of local growth and distal dissemination. The aim of our study was to determine the pattern of genetic alterations in human carcinomas of the exocrine pancreas orthotopically implanted and perpetuated in nude mice. Eight of the sixteen orthoimplanted human pancreatic carcinomas were perpetuated through several passages. Four perpetuated tumors followed distinct patterns of distal dissemination. Point mutations in the K-ras gene, genetic aberrations in the p53 and p16 genes, and allelic losses at retinoblastoma, adenomatous polyposis coli, and deleted in colorectal cancer loci were analyzed. Perpetuated tumors maintained the pattern of genetic alterations present in primary tumors. Five perpetuated tumors contained K-ras mutations, and all tumors contained p53 and/or p16 genetic aberrations. Allelic losses were present in four of the perpetuated tumors. Additional genetic alterations were detected in 6 of 35 metastases analyzed. Five of 9 peritoneal metastases or malignant ascitic cells acquired either K-ras or second p53 mutations. In contrast, only 1 of 25 liver metastases and none of the lymph node metastases acquired additional mutations. No additional p16 gene aberrations or other allelic losses were evidenced during tumor dissemination. We conclude that orthotopically implanted pancreatic carcinomas xenografted in nude mice show a high degree of genetic stability. Mutations in K-ras and p53 genes can occur in this model system in the more advanced stages of pancreatic tumor progression, mainly during peritoneal dissemination.
Assuntos
Adenocarcinoma/genética , Genes p53/genética , Neoplasias Pancreáticas/genética , Mutação Puntual/genética , Adenocarcinoma/secundário , Animais , Códon/genética , Genes ras/genética , Humanos , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Transplante HeterólogoRESUMO
1. Slices of rat cerebral cortex incubated aerobically at 37 degrees C in Krebs-Ringer-bicarbonate solution accumulated 3,4-L-dihydroxyphenylalanine (L-DOPA) against its concentration gradient. With 1 mM L-DOPA in the medium, tissue-water/medium concentration ratios of about 6 : 1 are reached, which are modified by the presence of other amino acids in the medium. 2. Kinetic analysis suggested that L-DOPA influx into brain cells occurred by at least two saturable processes, which show apparent Km values in the range of 10(-3) M and 10(-5) M, respectively. 3. Prior incubation of the slices in Na+-free (choline-containing) medium at 37 degrees C depressed their subsequent uptake of L-DOPA in normal Na+-containing medium; this inhibition did not appear when the preincubation was carried out at 0-4 degrees C. Besides this effect of preincubation, most of L-DOPA influx into brain slices was independent of the actual concentration of Na+ in the medium; the two saturable processes described in this article behaved similarly in this respect. 4. Most of L-DOPA uptake by the high-Km process is mediated by an agency that resembles the Na+-independent L system described in Ehrlich cells (Oxender, D. L. and Christensen, H. N. (1963) J. Biol. Chem. 238, 2686-2699), both in its specificity and in its participation in exchange phenomena. A lesser component of uptake by a type A mediation is also suggested as contributing to the high-Km process . 5. The kinetic and specificity properties of the low-Km process of L-DOPA uptake suggest a similarity between its mediation and that of the high-affinity systems for L-tyrosine and L-tryptophan found in brain tissue preparations (Belin, M. F. and Pujol, J. F. (1973) Experientia 29, 411-413; Bauman, A., Bourgoin, S., Benda, P., Glowinski, J. and Hamon, M. (1971 Brain Res. 66, 253-263).
Assuntos
Córtex Cerebral/metabolismo , Levodopa/metabolismo , Alanina/farmacologia , Aminoácidos/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Histidina/farmacologia , Cinética , Leucina/farmacologia , Masculino , Potássio/farmacologia , Ratos , Sódio/farmacologiaRESUMO
PURPOSE: p53 gene and K-ras mutations are among the most common genetic alterations present in colorectal cancer. The prognostic utility of such mutations remains controversial. The purpose of this study was to prospectively evaluate the prognostic significance of p53 and K-ras gene mutations in colorectal cancer. PATIENTS AND METHODS: One hundred forty patients were analyzed. Tumors belonging to the microsatellite mutator phenotype were excluded (n = 8). Mutations at the K-ras and p53 genes were detected and characterized by restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing, as appropriate. RESULTS: p53 mutations were detected in 66 (50%) and K-ras mutations were detected in 54 (41%) of the 132 patients. In 26 cases (20%), ras and p53 mutations coexisted; in 38 cases (29%), neither mutation was found. Multivariate analysis of the whole population analyzed (n = 132) showed that survival was strongly correlated with the presence of p53 mutations alone or in combination with K-ras mutations (P = .002; log-rank test). When only patients undergoing a radical resection were considered (R0; n = 101), p53 mutations were no longer of prognostic significance. CONCLUSION: p53 mutations alone or in combination with K-ras mutations are correlated with a worse outcome. However, the routine use of these mutations as prognostic markers in the clinical setting is not recommended.
Assuntos
Neoplasias Colorretais/genética , Genes p53/genética , Genes ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Códon/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prognóstico , Estudos Prospectivos , Análise de Regressão , Taxa de SobrevidaRESUMO
A sequel of supracondylar fractures of distal humerus in children is the angular deformity. It is usually more frequent cubitus varus, but there are reported cases of cubitus valgus. The latter may be the cause of the occurrence of a late ulnar nerve neuropathy, which will require treatment. There is controversy as to whether it is possible to successfully treat both problems at the same surgical procedure. This article describes the case of a girl of 11 years old, who has a cubitus valgus deformity secondary to supracondylar fracture of distal humerus of right elbow at the age of seven years, associated with progressive symptoms of ulnar nerve neuropathy. This patient was treated successfully by a single procedure for corrective dome-shaped supracondilar osteotomy associated with subcutaneous anterior transposition of the ulnar nerve through a posterior approach.
Una secuela de las fracturas supracondíleas de húmero distal en la infancia es la deformidad angular. Generalmente es más frecuente el cúbito varo, pero también existen casos descritos de cúbito valgo. Esta última puede ser la causa de la aparición de una neuropatía tardía del nervio cubital, que requerirá de tratamiento. Existe controversia en cuanto si es posible tratar con éxito ambos problemas en un mismo procedimiento quirúrgico. En este artículo se presenta el caso de una niña de 11 años, que presenta una deformidad en cúbito valgo secundaria a una fractura supracondílea de húmero distal de codo derecho a la edad de siete años, asociada con una clínica progresiva de neuropatía del nervio cubital. Esta paciente se trató de forma satisfactoria mediante un procedimiento único de osteotomía correctora cupuliforme supracondilar asociada con una transposición anterior subcutánea del nervio cubital a través de un abordaje posterior.
RESUMO
Iron overload is associated with free radical generation and tissue damage. Our main objective was to ascertain the frequency and severity of iron overload in a group of 59 patients who died after conventional-intensity autologous (n=24) or allogeneic (n=35) haematopoietic stem cell transplantation (HSCT). A second objective was to investigate associations between liver-iron concentration and causes of transplant-related mortality. The median age was 41 years (range, 19-66), 41 were males and 18 females. In total, 26 patients had acute leukaemia or MDS, 10 CML, 17 lymphoma, four myeloma and two aplastic anaemia. The median hepatic iron concentration (HIC) was 138 micromol/g dry weight (7.7 mg/g; range 31-631 micromol/g). In total, 4/32 (12%) patients with HIC <150 micromol/g and 10/27 (37%) with hepatic iron > or =150 micromol/g showed invasive aspergillosis at autopsy (P=0.035). This was significant in multivariate analysis (RR 9.0; 95% CI 1.6-50.3, P=0.012). In conclusion, severe iron overload is frequent in patients who die following HSCT and is associated with invasive aspergillosis.
Assuntos
Aspergilose/epidemiologia , Sobrecarga de Ferro/epidemiologia , Hepatopatias/epidemiologia , Transplante de Células-Tronco/efeitos adversos , Adulto , Idoso , Aspergilose/complicações , Feminino , Humanos , Sobrecarga de Ferro/complicações , Leucemia/terapia , Hepatopatias/complicações , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , EspanhaRESUMO
Gauze forgotten at operations can be potentially life threatening, but such cases are seldom reported because of the medicolegal implications. We have presented a series of seven patients with long-term surgical gauze retention, four after pelvic operations, one after cholecystectomy, one after laryngectomy, and one after mastectomy. The median time interval between operation and gauze removal was 5 years. In three patients this was diagnosed as a tumoral mass, in three as an intestinal occlusion, and in one the gauze was found incidentally. All foreign bodies were removed and no patient died. The clinical and diagnostic aspects of retained surgical gauze have been discussed and the need for radiopaque markers in them have been emphasized.
Assuntos
Corpos Estranhos/diagnóstico , Reação a Corpo Estranho/etiologia , Hemostasia Cirúrgica , Neoplasias/diagnóstico , Complicações Pós-Operatórias/etiologia , Bandagens , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A case of duplication of the patella in the coronal plane is reported. Previously reported cases of double patella have shown sagittal or vertical duplication, and some have been associated with multiple epiphyseal dysplasia. In our case, excision of one patella and realignment of the extensor mechanism relieved symptoms of giving-way.