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INTRODUCTION: Primary hyperparathyroidism (PHPT) caused by parathyroid tumours is mostly sporadic, with a genetic cause identified in 5-10% of cases. Familial parathyroid tumours can be included in complex syndromes, such as multiple endocrine neoplasia (MEN) type 1, 2A and 4 or hyperparathyroidism-jaw tumour syndrome (HPT-JT). OBJECTIVE: Characterisation of the familial parathyroid tumours followed-up at our centre and comparison of the different clinicopathological manifestations between the syndromes. METHODS: Retrospective analysis of 48 patients with familial parathyroid tumours harbouring RET (n = 11), CDC73 (n = 20) and MEN1 (n = 17) germline mutations was performed. RESULTS: Cases of PHPT in MEN2A syndrome presented with lower serum PTH (sPTH) and serum calcium (sCa) levels at diagnosis (sPTH = 108.0 (IQR 53.3) pg/mL, sCa = 10.6 ± 1.1 mg/dL) than MEN1 (sPTH = 196.9 (IQR 210.5) pg/mL, sCa = 11.7 ± 1.2 mg/dL) (p = 0.01, p = 0.03, respectively) or HPT-JT cases (sPTH = 383.5 (IQR 775.8) pg/mL, sCa = 12.9 ± 1.8 mg/dL) (p = 0.01; p < 0.001, respectively). There was a statistical difference in sCa levels between MEN1 and HPT-JT (p = 0.02), but not between sPTH (p = 0.07). The predominant first manifestation of the syndrome in MEN1 was gastroenteropancreatic neuroendocrine tumour (GEP-NET) in 47.1% of the cases, in MEN2A was medullary thyroid cancer (90.9%) and in HPT-JT was PHPT in 85% patients. In MEN1 syndrome, the number of affected parathyroid glands was significantly higher than in MEN2A (p < 0.001) and HPT-JT (p = 0.01). CONCLUSION: The first manifestation of the syndrome in MEN1 cases was GEP-NET and not PHPT. Although presenting at similar ages, patients with MEN2A exhibit less severe biochemical and clinical PHPT at diagnosis than the other familial syndromes.
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Neoplasia Endocrina Múltiple Tipo 1 , Neoplasia Endocrina Múltiple Tipo 2a , Neoplasias de las Paratiroides , Humanos , Glándulas Paratiroides , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/genética , Neoplasia Endocrina Múltiple Tipo 2a/genética , Síndrome , Estudios Retrospectivos , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/genéticaRESUMEN
PURPOSE: Medullary thyroid carcinoma (MTC) displays a wide variety of histopathological features, and several histological variants have been described. In follicular cell-derived thyroid carcinomas, there is a good correlation between genotype and phenotype. In this study, we investigated whether such a correlation is also present in MTC. METHODS: The histopathological features were evaluated in a series of 66 molecularly characterised tumours and correlated with the clinical characteristics. RESULTS: Most MTC exhibited the classical variant (83.3%). Other variants included spindle cell (6.1%), pseudopapillary (4.5%), paraganglioma-like (3.0%), angiosarcoma-like (1.5%), and oncocytic follicular (1.5%). Tumours were classified into four groups: group 1, with somatic p.Met918Thr and p.Ala883Phe RET mutations; group 2, with other RET mutations; group 3, with RAS mutations; and group 4, without RET or RAS mutations. Tumours from groups 1 and 4 were typically associated with the classical variant, with abundant fibrosis, lymphovascular invasion, extrathyroidal extension, and more advanced stages of disease, whereas group 2 included histological variants other than the classical variant (namely, pseudopapillary and paraganglioma-like), with tumours that were highly cellular, less invasive, and with a better overall prognosis. In tumours from group 4, amyloid deposition was characteristically absent or low. The spindle cell variant appeared only in tumours from group 3, which had high cellularity and a degree of invasion and prognosis intermediate between groups 1 and 2, but better than group 4. The grade of fibrosis correlated directly with the clinical outcome. CONCLUSION: Our results support the idea that a genotype-phenotype correlation does, indeed, exist in MTC. However, further studies are warranted to confirm these findings in a larger sample size.
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Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Adulto , Anciano , Anciano de 80 o más Años , Amiloide/metabolismo , Carcinoma/metabolismo , Carcinoma/patología , Femenino , Fibrosis , Genes ras/genética , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Invasividad Neoplásica , Patología Molecular , Pronóstico , Proteínas Proto-Oncogénicas c-ret/genética , Estudios RetrospectivosRESUMEN
The presence of glandular appendages in the anthers is a rare condition in angiosperms. In Leguminosae it occurs in species of the Mimosoid clade and in early-branching clades of papilionoids such as Dipterygeae. In Dipterygeae such appendages surprisingly exhibit a secretory cavity instead of secretory emergences as is the case for the Mimosoid clade. Thus, the objective of this study was to elucidate the function of anther glands in Dipteryx alata and Pterodon pubescens, species in the Dipterygeae clade that exhibit a pollen release mechanism that is intermediate between the explosive and valvular types. Flower buds and flowers were processed for surface, anatomical, histochemical and ultrastructural analyses. Anther glands consist of a cavity secreting sticky substances (oleoresins and polysaccharides) that play a key role during the flower's lifespan by aggregating pollen grains and attaching them to the floral visitor's body. Other floral features that are important for understanding the pollen release mechanism that is intermediate between the valvular and the explosive types are: (i) keel petals intertwined with tector trichomes; (ii) glandular appendages in the abaxial and lateral sepals and in petals composed of secretory ducts; and (iii) a continuous secretion process of the anther glands followed by an asynchronous dehiscence of anthers. The well-adapted papilionoid flag blossom with anther glands and keel petals intertwined with trichomes provided the foundation for a successful canalisation toward a pollen release mechanism intermediate between the explosive and valvular types inside early-branching papilionoids.
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Fabaceae/fisiología , Flores/fisiología , Polinización/fisiología , Dipteryx/metabolismo , Dipteryx/fisiología , Fabaceae/metabolismo , Flores/metabolismo , Extractos Vegetales/metabolismo , Polisacáridos/metabolismoRESUMEN
PURPOSE: The EIF1AX gene was recently described as a new thyroid cancer-related gene. Its mutations were mainly reported in poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), but also in well-differentiated thyroid cancer (WDTC) and in benign thyroid lesions, although less frequently. Our aim was to address whether EIF1AX mutations are present in the different stages of thyroid tumourigenesis (from hyperplasia to well-differentiated and to poorly differentiated/undifferentiated lesions), and to clarify its role in this process. METHODS: We analysed the EIF1AX gene in a series of 16 PDTC and ATC cases with coexistent well-differentiated regions and/or benign lesions. In EIF1AX mutant cases we also assessed the presence of RAS genes mutations. RESULTS: We identified the mutation p.Ala113_splice in the EIF1AX gene in two PDTCs (neither present in the well-differentiated counterparts nor in the benign areas). One of these tumours also evidenced the mutation p.Glu61Arg in NRAS in both poorly and well-differentiated regions, further suggesting that the EIF1AX p.Ala113_splice mutation could be associated with tumoural progression. In another patient we did not find any EIF1AX alteration in the PDTC component, but we detected the EIF1AX p.Gly6_splice mutation in the PTC area (both regions were RAS wild-type). This mutation did not seem to be related with dedifferentiation. CONCLUSIONS: According to our results, distinct mutations on EIF1AX may be related to different phenotypes/behaviours. Despite being a small series, which reflects the difficulty in retrieving PDTC and ATC surgical samples with well-differentiated and/or benign areas, our study may provide new insights into thyroid cancer tumourigenesis and dedifferentiation.
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Adenocarcinoma/patología , Carcinogénesis/patología , Factor 1 Eucariótico de Iniciación/genética , Mutación , Regiones Promotoras Genéticas , Neoplasias de la Tiroides/patología , Adenocarcinoma/genética , Carcinogénesis/genética , Progresión de la Enfermedad , Femenino , Genes ras , Humanos , Masculino , Pronóstico , Empalme del ARN , Neoplasias de la Tiroides/genéticaRESUMEN
PURPOSE: Anaplastic thyroid carcinomas (ATCs) are non-responsive to multimodal therapy, representing one of the major challenges in thyroid cancer. Previously, our group has shown that genes involved in cell cycle are deregulated in ATCs, and the most common mutations in these tumours occurred in cell proliferation and cell cycle related genes, namely TP53, RAS, CDKN2A and CDKN2B, making these genes potential targets for ATCs treatment. Here, we investigated the inhibition of HRAS by tipifarnib (TIP) and cyclin D-cyclin-dependent kinase 4/6 (CDK4/6) by palbociclib (PD), in ATC cells. METHODS: ATC cell lines, mutated or wild type for HRAS, CDKN2A and CDKN2B genes, were used and the cytotoxic effects of PD and TIP in each cell line were evaluated. Half maximal inhibitory concentration (IC50) values were determined for these drugs and its effects on cell cycle, cell death and cell proliferation were subsequently analysed. RESULTS: Cell culture studies demonstrated that 0.1 µM TIP induced cell cycle arrest in the G2/M phase (50%, p < 0.01), cell death, and inhibition of cell viability (p < 0.001), only in the HRAS mutated cell line. PD lowest concentration (0.1 µM) increased significantly cell cycle arrest in the G0/G1 phase (80%, p < 0.05), but only in ATC cell lines with alterations in CDKN2A/CDKN2B genes; additionally, 0.5 µM PD induced cell death. The inhibition of cell viability by PD was more pronounced in cells with alterations in CDKN2A/CDKN2B genes (p < 0.05) and/or cyclin D1 overexpression. CONCLUSIONS: This study suggests that TIP and PD, which are currently in clinical trials for other types of cancer, may play a relevant role in ATC treatment, depending on the specific tumour molecular profile.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas Proto-Oncogénicas p21(ras)/antagonistas & inhibidores , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/patología , Apoptosis , Ciclo Celular , Proliferación Celular , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 6 Dependiente de la Ciclina/genética , Humanos , Mutación , Piperazinas/administración & dosificación , Proteínas Proto-Oncogénicas p21(ras)/genética , Piridinas/administración & dosificación , Quinolonas/administración & dosificación , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/genética , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Células Tumorales CultivadasRESUMEN
This study aims to evaluate the use of assistive devices as a strategy in non-pharmacological treatment for hand osteoarthritis (HOA). This is a randomized, prospective, parallel, assessor-blinded clinical trial, in which patients with a diagnosis of HOA were randomly allocated to an intervention group (IG), where they received assistive devices for daily life activities, or to a control group (CG), where they received a guideline leaflet with information on joint protection and disease features. The primary outcomes considered were occupational performance, measured by the Canadian Occupational Performance Measure (COPM), and hand function was evaluated through the Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (SACRAH). The secondary outcomes were pain, measured by the visual analog scale (VAS), and quality of life, measured by the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF). We compared both outcomes before and after interventions and outcomes between groups. Participants from the two groups were assessed at the time of inclusion in the study, 30, and 90 days after initial evaluation. Out of the 39 patients included, 19 were allocated to the IG and 20 to the CG. Only two patients from the CG did not complete the follow-up period. The patients' hand function and occupational performance improved after intervention (30 days-SACRAH-p < 0.05; COPM-p < 0.05; VAS-p < 0.05). When comparing results between the groups, there was a statistical difference in COPM (performance-p < 0.001; and satisfaction-p < 0.001), in the first reevaluation carried out. The use of assistive devices has proved to be an effective alternative in non-pharmacological treatment for HOA. CLINICAL TRIAL REGISTRATION: NCT02667145.
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Actividades Cotidianas , Ergonomía , Articulaciones de la Mano/fisiopatología , Artículos Domésticos , Osteoartritis/terapia , Dispositivos de Autoayuda , Anciano , Fenómenos Biomecánicos , Brasil , Evaluación de la Discapacidad , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/diagnóstico , Osteoartritis/fisiopatología , Dimensión del Dolor , Estudios Prospectivos , Calidad de Vida , Recuperación de la Función , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
Activating germline mutations in the RET proto-oncogene are responsible for about 98 % of the familial forms of medullary thyroid carcinoma (MTC), which represent 25 % of all MTC cases. The search for germline mutations in this gene is important for the recognition of hereditary forms of MTC and further identification of at-risk relatives who may benefit from early clinical intervention. Genotype-phenotype correlations are well established for most disease-causing RET mutations, allowing risk stratification. The association of a new RET variant with the MTC phenotype and familial predisposition requires the assessment of its functional and clinical significance. The aim of this study was to evaluate the oncogenic potential of two newly identified RET germline variants associated with late-onset MTC. In vitro functional assays were designed to address the transforming potential of novel RET variants, through their expression in non-transformed cells, and comparing their effect with wild-type RET. The new variants were identified in codons 515 (p.C515W) and 636 (p.T636M) located, respectively, in exons 8 and 11, thus resulting in amino acid substitutions in the extracellular region of the tyrosine kinase receptor RET. Through functional assays, we observed increased cell growth and proliferation, loss of contact inhibition, and a stimulation of cell migration, suggesting that these new RET variants hold some relevant transforming potential. The transforming potential of these novel RET variants was of low-grade, when compared to that of RET MEN2A-causing mutation p.C634R, probably explaining the mild phenotype characterized by late onset and low clinical aggressiveness.
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Carcinoma Neuroendocrino/genética , Mutación de Línea Germinal/genética , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasias de la Tiroides/genética , Edad de Inicio , Anciano , Carcinoma Neuroendocrino/fisiopatología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 2a/genética , Fenotipo , Proto-Oncogenes Mas , Neoplasias de la Tiroides/fisiopatologíaRESUMEN
Maytenus ilicifolia (Celastraceae), popularly known as espinheira-santa, is a native plant from the Atlantic forest and is commonly used in popular medicine to treat inflammation and as an abortifacient. To evaluate the effects of M. ilicifolia on pregnant rats during the organogenic period (T1) or throughout the gestational period (T2), an extract obtained using an acetone-water mixture at a 70:30 ratio was administered via gavage at a dose of 15.11 mg·kg(-1)·day(-1) over 2 treatment periods (T1 and T2). No clinical signs of maternal toxicity were observed. Term fetuses did not present malformations or anomalies as the number of implantations, reabsorptions, live, and dead fetuses were similar to the control group. In conclusion, M. ilicifolia hydroacetonic extract is non-toxic to pregnant rats and appears to not interfere with the progress of embryo-fetal development.
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Desarrollo Embrionario/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Reproducción/efectos de los fármacos , Animales , Embrión de Mamíferos/efectos de los fármacos , Femenino , Maytenus/química , Extractos Vegetales/química , Embarazo , Ratas , Ratas WistarRESUMEN
The aim of this study was to identify the most adequate level of calcium oxide (CaO) in the treatment of sugar cane by evaluating the chemical composition and in vitro digestibility of dry matter. The sugar cane was homogenized with CaO levels 0, 0.75, 1.5, 2.25, 3.0, 3.75 and 4.5 percent, in natura matter, for 24 hours. The dry matter and mineral matter increased, while the organic matter of the sugar cane decreased (P <0.05) linearly as a result of the CaO levels. The CaO had no effect on the levels of crude protein and ether extract. The phosphorus concentration remained unchanged, but there was a significant increase (P<0.05) in the calcium content. The contents of neutral detergent fiber, acid detergent fiber and cellulose decreased linearly with the levels of CaO. The average levels of indigestible dry matter and indigestible neutral detergent fiber significantly decreased with increasing levels of CaO. The results showed that the in vitro dry matter digestibility (IVDMD) was different between fresh sugar cane and sugar cane with added levels of CaO from 1.5 percent. The IVDMD and nutritional value of the sugar cane was improved by adding 1.5 percent CaO based on fresh content...
O objetivo foi identificar o nível mais adequado de óxido de cálcio (CaO) no tratamento da cana-de-açúcar por meio da avaliação da composição química e a digestibilidade in vitro da matéria seca. A cana-de-açúcar foi homogeneizada adicionando os níveis de CaO 0; 0,75; 1,5; 2,25; 3,0; 3,75 e 4,5 por cento em porcentagem de matéria natural, por 24 horas. Os teores de matéria seca e matéria mineral aumentaram, ao passo que o teor de matéria orgânica da cana-de-açúcar diminuiu (P<0,05) de forma linear em função dos níveis de CaO. Não houve efeito dos níveis do CaO sobre o teor de proteína bruta e extrato etéreo. Os teores médios de fósforo mantiveram-se inalterados, porém ocorreu um aumento (P<0,05) no teor de cálcio. Os teores de fibra em detergente neutro, fibra em detergente ácido e celulose diminuíram linearmente em função dos níveis de CaO. Os teores médios da matéria seca indigestível e da fibra em detergente neutro indigestível tiveram redução significativa com o aumento dos níveis de CaO. Os resultados da digestibilidade in vitro da matéria seca (DIVDM) mostraram-se diferentes entre cana-de-açúcar in natura e a com níveis de CaO. Níveis de CaO a partir de 1,5 por cento melhoram o valor nutritivo e a DIVDM da cana-de-açúcar...
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Óxido de Calcio , Saccharum , Saccharum/química , Bovinos , Digestión , Materia OrgánicaRESUMEN
Crustaceans show discontinuous growth and have been used as a model system for studying cellular mechanisms of calcium transport, which is the main mineral found in their exoskeleton. Ucides cordatus, a mangrove crab, is naturally exposed to fluctuations in calcium and salinity. To study calcium transport in this species during isosmotic conditions, dissociated gill cells were marked with fluo-3 and intracellular Ca(2+) change was followed by adding extracellular Ca(2+) as CaCl2 (0, 0.1, 0.25, 0.50, 1.0 and 5mM), together with different inhibitors. For control gill cells, Ca(2+) transport followed Michaelis-Menten kinetics with Vmax=0.137±0.001 ∆Ca(2+)i (µM×22.10(4)cells(-1)×180s(-1); N=4; r(2)=0.99); Km=0.989±0.027mM. The use of different inhibitors for gill cells showed that amiloride (Na(+)/Ca(2+) exchange inhibitor) inhibited 80% of Ca(2+) transport in gill cells (Vmax). KB-R, an inhibitor of Ca influx in vertebrates, similarly caused a decrease in Ca(2+) transport and verapamil (Ca(2+) channel inhibitor) had no effect on Ca(2+) transport, while nifedipine (another Ca(2+) channel inhibitor) caused a 20% decrease in Ca(2+) affinity compared to control values. Ouabain, on the other hand, caused no change in Ca(2+) transport, while vanadate increased the concentration of intracellular calcium through inhibition of Ca(2+) efflux probably through the plasma membrane Ca(2+)-ATPase. Results show that transport kinetics for Ca(2+) in these crabs under isosmotic conditions is lower compared to a hyper-regulator freshwater crab Dilocarcinus pagei studied earlier using fluorescent Ca(2+) probes. These kinds of studies will help understanding the comparative mechanisms underlying the evolution of Ca transport in crabs living in different environments.
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Braquiuros/metabolismo , Calcio/metabolismo , Branquias/metabolismo , Tolerancia a la Sal , Animales , Proteínas de Artrópodos/metabolismo , Braquiuros/fisiología , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/metabolismo , Branquias/citología , Cinética , Salinidad , Vanadatos/farmacología , Verapamilo/farmacología , HumedalesRESUMEN
Avaliaram-se o fracionamento de carboidratos e a degradabilidade in situ da matéria seca (MS) e da fibra em detergente neutro (FDN) da cana-de-açúcar tratada com óxido de cálcio (CaO). Foram testadas as porcentagens de 0; 0,75; 1,5; 2,25; 3,0; 3,75 e 4,5% de CaO, e o material testemunha (cana-de-açúcar in natura) para a avaliação do fracionamento de carboidratos, e as porcentagens de 0; 1,5; 3,0 e 4,5% de CaO para a avaliação da degradabilidade in situ da MS e da FDN. O CaO foi adicionado em pó na cana-de-açúcar, em porcentagem da matéria natural, por 24 horas. A porcentagem de inclusão de CaO na cana-de-açúcar proporcionou valores mais baixos para teores de carboidratos totais (CT) comparados aos valores da cana-de-açúcar in natura. Observou-se crescimento linear das frações A+B1 e B2, e redução na fração C da cana-de-açúcar em função da porcentagem de CaO. Os maiores valores de fração insolúvel potencialmente degradável da MS e menores de fração indigestível (Ip) da FDN foram observados na cana-de-açúcar com 3,0 e 4,5% de CaO. A adição de 3,0 e 4,5% de CaO na cana-de-açúcar promove diminuição da fração indigestível dos carboidratos e melhores taxas de degradação ruminal tanto da MS quanto da FDN.
Were evaluated the fractioning of carbohydrates and in situ dry matter (DM) and neutral detergent fiber (NDF) of sugarcane treated with calcium oxide (CaO). Levels 0, 0.75, 1.5, 2.25, 3.0, 3.75 and 4.5% CaO, and the material witness (sugarcane in nature) were tested for the assessment of fractioning of carbohydrates and levels 0, 1.5, 3.0 and 4.5% CaO for the evaluation of in situ DM and NDF. The levels of CaO were added in powder form, as a percentage of natural matter in sugarcane for 24 hours. The inclusion levels of CaO in sugarcane showed lower values for the total carbohydrates (TC) when compared with sugarcane in natura. A linear growth of the fractions A + B1 and B2 was observed, as well as a decrease in C fraction of sugarcane depending on the levels of CaO. The highest values of insoluble fraction potentially degradable in rumen and the lower values of NDF indigestible fraction (Ip) were observed in sugarcane with 3.0 and 4.5% CaO. The addition of 3.0 and 4.5% CaO to sugarcane decreased the indigestible carbohydrates fraction and promotes better rates of ruminal degradation of both DM and NDF.
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Animales , Carbohidratos/análisis , Óxido de Calcio/análisis , Fenómenos Químicos , SaccharumRESUMEN
UNLABELLED: The superoxide dismutase (TfSOD) gene from the extremely thermophilic bacterium Thermus filiformis was cloned and expressed at high levels in mesophilic host. The purified enzyme displayed approximately 25 kDa band in the SDS-PAGE, which was further confirmed as TfSOD by mass spectrometry. The TfSOD was characterized as a cambialistic enzyme once it had enzymatic activity with either manganese or iron as cofactor. TfSOD showed thermostability at 65, 70 and 80°C. The amount of enzyme required to inhibit 50% of pyrogallol autoxidation was 0·41, 0·56 and 13·73 mg at 65, 70 and 80°C, respectively. According to the circular dichroism (CD) spectra data, the secondary structure was progressively lost after increasing the temperature above 70°C. The 3-dimensional model of TfSOD with the predicted cofactor binding corroborated with functional and CD analysis. SIGNIFICANCE AND IMPACT OF THE STUDY: This manuscript describes the expression and characterization of a superoxide dismutase (SOD) from Thermus filiformis with thermophilic and cambialistic characteristics. The SODs are among the most potent antioxidants known in nature, and their stability and pharmacokinetics can vary widely in accordance to their biological source. Although the currently clinical research work has been focused on human and bovine SODs, alternative sources may become more biotechnological attractive in the near future. Our study brings new insights for the research field of antioxidant enzymes with potential application on pharmaceutical, cosmetics and food formulations.
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Superóxido Dismutasa/química , Superóxido Dismutasa/genética , Thermus/enzimología , Thermus/genética , Dicroismo Circular , Clonación Molecular , Coenzimas/metabolismo , Estabilidad de Enzimas , Hierro/metabolismo , Manganeso/metabolismo , Modelos Moleculares , Desnaturalización Proteica , Estructura Secundaria de Proteína , Superóxido Dismutasa/metabolismo , Temperatura , Thermus/metabolismoRESUMEN
Twenty-five percent of medullary thyroid cancers (MTC) are familial and inherited as an autosomal dominant trait. Three different phenotypes can be distinguished: multiple endocrine neoplasia (MEN) types 2A and 2B, in which the MTC is associated with other endocrine neoplasias, and familial MTC (FMTC), which occurs in isolation. The discovery that germline RET oncogene activating mutations are associated with 95-98% of MEN 2/FMTC syndromes and the availability of genotyping to identify mutations in affected patients and their relatives has revolutionized the diagnostic and therapeutic strategies available for the management of these patients. All patients with MTC, both those with a positive familial history and those apparently sporadic, should be submitted to RET genetic screening. Once an RET mutation has been confirmed in an index patient, first-degree relatives should be screened rapidly to identify the 50% who inherited the mutation and are therefore at risk for development of MTC. Relatives in whom no RET mutation is identified can be reassured and discharged from further follow-up, whereas RET-positive subjects (i.e. gene carriers) must be investigated and a therapeutic strategy initiated. These guideline recommendations are derived from the most recent studies identifying phenotype-genotype correlations following the discovery of causative RET gene mutations in MEN 2 eighteen years ago. Three major points will be discussed: (a) identification of patients and relatives who should have genetic screening for RET mutations, (b) management of asymptomatic gene carriers, and (c) ethics.
RESUMEN
BACKGROUND: Acute normovolemic hemodilution (ANH) is an alternative to blood transfusion in surgeries involving blood loss. This experimental study was designed to evaluate whether pulse pressure variation (PPV) would be an adequate tool for monitoring changes in preload during ANH, as assessed by transesophageal echocardiography. METHODS: Twenty-one anesthetized and mechanically ventilated pigs were randomized into three groups: CTL (control), HES (hemodilution with 6% hydroxyethyl starch at a 1:1 ratio) or NS (hemodilution with saline 0.9% at a 3:1 ratio). Hemodilution was performed in animals of groups NS and HES in two stages, with target hematocrits 22% and 15%, achieved at 30-minute intervals. After two hours, 50% of the blood volume withdrawn was transfused and animals were monitored for another hour. Statistical analysis was based on ANOVA for repeated measures followed by multiple comparison test (P<0.05). Pearson's correlations were performed between changes in left ventricular end-diastolic volume (LVEDV) and PPV, central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP). RESULTS: Group NS received a significantly greater amount of fluids during ANH (NS, 900 ± 168 mL vs. HES, 200 ± 50 mL, P<0.05) and presented greater urine output (NS, 2643 ± 1097 mL vs. HES, 641 ± 338 mL, P<0.001). Significant decreases in LVEDV were observed in group NS from completion of ANH until transfusion. In group HES, only increases in LVEDV were observed, at the end of ANH and at transfusion. Such changes in LVEDV (∆LVEDV) were better reflected by changes in PPV (∆PPV, R=-0.62) than changes in CVP (∆CVP, R=0.32) or in PAOP (∆PAOP, R=0.42, respectively). CONCLUSION: Changes in preload during ANH were detected by changes in PPV. ∆PPV was superior to ∆PAOP and ∆CVP to this end.
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Presión Sanguínea/fisiología , Volumen Sanguíneo/fisiología , Hemodilución/métodos , Animales , Superficie Corporal , Peso Corporal/fisiología , Presión Venosa Central/fisiología , Coloides/uso terapéutico , Soluciones Cristaloides , Ecocardiografía Transesofágica , Corazón/fisiología , Hemodinámica/fisiología , Soluciones Isotónicas/uso terapéutico , Sustitutos del Plasma/uso terapéutico , Arteria Pulmonar/fisiología , PorcinosRESUMEN
BACKGROUND: The incidence of thyroglossal duct cyst (TDC) carcinoma is uncommon (approximately 1%) and rarely reported in the literature. Treatment modalities have included tumourectomy, Sistrunk's procedure and/or total thyroidectomy. AIM: To try and determine the most adequate surgical approach for papillary thyroid carcinoma (PTC) arising in TDC. RESULTS: We reviewed the clinical charts of 22 patients with PTC of TDC treated between January 1974 and December 2008 (0.63% of the total of 3458 patients with PTC treated over that period). All patients underwent the Sistrunk's procedure. Fourteen (64%) were submitted to total thyroidectomy and 11 of these patients were ablated with lodine131. Seven (50%) of the 14 patients treated with total thyroidectomy had tumour both in the thyroid gland and in TDC but lymph node metastases were present only in four. None of the patients died of the disease and all of them are still alive without recurrence with a mean follow-up of 8 years (range: 2-27 years). The mean survival rate of the patients submitted to total thyroidectomy (n= 14) was not statistically different from that of patients treated with the Sistrunk's procedure alone (9.23 +/- 7.65 vs. 8.95 +/- 6.22, p= 0.940). CONCLUSION: Papillary thyroid carcinoma arising in thyroglossal duct cysts is a very rare malignant tumour. In spite of the multifocal character of several of our cases, their analysis showed that the prognosis in the vast majority of patients with TDC carcinoma is excellent. Moreover, we found no relation between outcome and surgical procedure.
Asunto(s)
Carcinoma Papilar/patología , Quiste Tirogloso/patología , Neoplasias de la Tiroides/patología , Adolescente , Adulto , Carcinoma Papilar/terapia , Femenino , Humanos , Radioisótopos de Yodo/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Quiste Tirogloso/terapia , Neoplasias de la Tiroides/terapia , Tiroidectomía , Adulto JovenRESUMEN
BACKGROUND: There are no reports on the long-term follow-up of patients with swine-origin influenza A virus infection that progressed to acute respiratory distress syndrome. METHODS: Four patients were prospectively followed up with pulmonary function tests and high-resolution computed tomography for six months after admission to an intensive care unit. RESULTS: Pulmonary function test results assessed two months after admission to the intensive care unit showed reduced forced vital capacity in all patients and low diffusion capacity for carbon monoxide in two patients. At six months, pulmonary function test results were available for three patients. Two patients continued to have a restrictive pattern, and none of the patients presented with abnormal diffusion capacity for carbon monoxide. All of them had a diffuse ground-glass pattern on high-resolution computed tomography that improved after six months. CONCLUSIONS: Despite the marked severity of lung disease at admission, patients with acute respiratory distress syndrome caused by swine-origin influenza A virus infection presented a late but substantial recovery over six months of follow-up.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/complicaciones , Síndrome de Dificultad Respiratoria/virología , Adulto , Estudios de Seguimiento , Humanos , Unidades de Cuidados Intensivos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Recuperación de la Función , Respiración Artificial , Síndrome de Dificultad Respiratoria/fisiopatología , Pruebas de Función Respiratoria , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
A laboratory model of myiasis as a result of Dermatobia hominis (L.) larvae was developed using mice as hosts. Mice in three groups were each infested with one newly hatched larva and skin biopsies processed for histopathology at 4, 12, and 20 d postinfestation (dpi). Mice in three other groups were each subjected to implantation of one larva collected from an infested (donor) mouse at 4, 12, and 20 dpi. Skin lesions of these receptor mice were then assessed at 10, 14, and 6 d postimplantation (dpimp), respectively. The inflammatory process in infested mice at 4 dpi was discrete, consisting of a thin necrotic layer around the larva, edema, many neutrophils, few eosinophils, mast cells, and proliferation of fibroblasts. At 12 dpi, there was a thicker necrotic layer, edema, many neutrophils and eosinophils, few mast cells, neoformation of capillaries, proliferation of the endothelium and fibroblasts, and early stages of fibrosis. These histopathological characteristics together with fibrosis were observed over a large area of the lesion at 20 dpi. Mice submitted to larval implantations demonstrated similar skin histopathology to that seen in the infested rodents, 10 dpimp corresponding to 12 dpi and 6 or 14 dpimp to 20 dpi. In all mice, the progressive acute inflammatory process followed a sequence linked to factors such as size of larvae and presence of secretory-excretory products. Both infested mice and those implanted experimentally with D. hominis larvae were shown to be suitable models for the study of the parasite-host relationship in this important zoonotic myiasis.
Asunto(s)
Dípteros/fisiología , Modelos Animales de Enfermedad , Miasis/patología , Piel/patología , Animales , Dípteros/crecimiento & desarrollo , Interacciones Huésped-Parásitos , Larva/fisiología , Ratones , Miasis/inmunología , Miasis/parasitología , Piel/inmunología , Piel/parasitologíaRESUMEN
This study evaluates the performance of four 2.3 m deep pilot-scale, independently loaded, primary facultative ponds treating predominantly domestic sewage in northeast Brazil. The ponds contained longitudinal baffles giving different length to width ratios from 3.55 to 32.4. The ponds had mean hydraulic retention times of ~15 days, and mean surface organic loadings of 330 kg BOD(5).ha.d(-1) during the first experimental phase and 375 kg BOD(5).ha.d(-1) in the second. The vertical inlets and outlets pipes were positioned at 1.8 m and 5 cm respectively below the pond surface in the first phase and at 50 cm and 1.8 m respectively in the second. All the ponds functioned as efficient primary facultative ponds but statistical analysis demonstrated no differences in effluent quality for most of the parameters measured for the various configurations of baffles and inlet and outlet depths. All behaved similarly to the unbaffled pond. The only exceptions were suspended solids and chlorophyll a concentrations which tended to be lower for all combinations of baffles with the outlets set 1.8 m below the surface. This study suggested that the longitudinal baffling of primary facultative ponds when using vertical inlets and outlets may well not significantly improve pond performance.
Asunto(s)
Eliminación de Residuos Líquidos , Purificación del Agua/métodos , Biodegradación Ambiental , Reactores Biológicos , Brasil , Composición Familiar , Proyectos Piloto , Abastecimiento de AguaRESUMEN
This study evaluated the efficiency of a shallow (0.5 m deep) waste stabilization pond series to remove high concentrations of ammonia from sanitary landfill leachate. The pond system was located at EXTRABES, Campina Grande, Paraiba, Northeast Brazil. The pond series was fed with sanitary landfill leachate transported by road tanker to the experimental site from the sanitary landfill of the City of Joao Pessoa, Paraiba. The ammoniacal-N surface loading on the first pond of the series was equivalent to 364 kg ha(-1) d(-1) and the COD surface loading equivalent to 3,690 kg ha(-1) d(-1). The maximum mean ammonia removal efficiency was 99.5% achieved by the third pond in the series which had an effluent concentration of 5.3 mg L(-1) ammoniacal-N for an accumulative HRT of 39.5 days. The removal process was mainly attributed to ammonia volatilization (stripping) from the pond surfaces as a result of high surface pH values and water temperatures of 22-26°C. Shallow pond systems would appear to be a promising technology for stripping ammonia from landfill leachate under tropical conditions.
Asunto(s)
Amoníaco/aislamiento & purificación , Administración de Residuos/métodos , Amoníaco/análisis , Oxígeno/química , Clima TropicalRESUMEN
BACKGROUND: There are no reports on the long-term follow-up of patients with swine-origin influenza A virus infection that progressed to acute respiratory distress syndrome. METHODS: Four patients were prospectively followed up with pulmonary function tests and high-resolution computed tomography for six months after admission to an intensive care unit. RESULTS: Pulmonary function test results assessed two months after admission to the intensive care unit showed reduced forced vital capacity in all patients and low diffusion capacity for carbon monoxide in two patients. At six months, pulmonary function test results were available for three patients. Two patients continued to have a restrictive pattern, and none of the patients presented with abnormal diffusion capacity for carbon monoxide. All of them had a diffuse ground-glass pattern on high-resolution computed tomography that improved after six months. CONCLUSIONS: Despite the marked severity of lung disease at admission, patients with acute respiratory distress syndrome caused by swine-origin influenza A virus infection presented a late but substantial recovery over six months of follow-up.