993 resultados para G.1.6 Optimization
Resumo:
Fueron estudiadas en forma comparativa 6 cepas de P. brasiliensis con el propósito de determinar su patogenicidad para la rata y su antigenicidad. Las mismas fueron aisladas de : 1) biopsia de cuello uterino en 1989 (U), 2) biopsia de mucosa bucal en 1988 (V), 3) aspiración ósea en 1991 (63265), 4) testículo de cobayo 1984(C24), 5) punción-aspiración ganglionaren 1986 (G) y 6) cepa proveniente de la Escola Paulista de Medicina (339). Se prepararon antigenos citoplasmáticos liofilizados de cada una de ellas, en la concentración final de 100 mg/ml y se realizaron pruebas de inmunodifusión frente a 6 sueros patrones positivos de ratas. En este ensayo todos los antígenos presentaron dos ó tres bandas de precipitación. Para estudiar el poder patógeno se inocularon, en total, 120 ratas Wistar, de ambos sexos de 200 g de peso, por via intracardíaca con suspensiones de la fase levaduriforme del P. brasiliensis, en concentraciones de 3x10(7) y 5x10(7) células/ml de cada cepa. Los animales que no murieron espontáneamente fueron sacrificados a los 14,28,42, 56 y 70 dias post-infección y se evaluaron los siguientes parámetros: A) exámenes macro y microscópicos de pulmones, hígado, bazo y riñones; B) cultivos de un pulmón y C) prueba de inmunodifusión con antígeno homólogo. Se consideró además, el porcentaje de muertes espontáneas por cada cepa. Los resultados de estos estudios fueron los siguientes:No se observó relación entre la patogenicidad y la antigenicidad. La cepa más virulenta correspondió a un aislamiento reciente a partir de una forma juvenil grave y la más antigénica fue una cepa, morfológicamente atípica, que no provocó lesiones macroscópicas ni microscópicas en los órganos de las ratas.
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Neste estudo procedeu-se à caracterização da diversidade genética das regiões codificantes da protease (PR), transcritase reversa (RT) e integrase (IN) do gene pol do vírus da imunodeficiência humana tipo 1 (HIV-1), bem como à pesquisa de polimorfismos genéticos associados à diminuição da susceptibilidade aos anti-retrovirais inibidores enzimáticos, circulante numa população de 51 indivíduos utilizadores de drogas por via endovenosa (IDUs) da Grande Lisboa. Em termos globais, a análise filogenética realizada com base em 38 sequências nucleotídicas concatenadas revelou que 12 (31,6%), 13 (34,2%) e 13 (34,2%) das sequências analisadas eram dos subtipos B, G/CRF14_BG e de formas genéticas não-B/não-G (1 F1, 4 CRF02_AG e 8 formas recombinantes únicas), respectivamente. Relativamente à pesquisa de mutações associadas a resistência (perfil genotípico), foram encontradas 15, presentes em 50,0% (22/44) dos indivíduos, com uma distribuição de 1-3/indivíduo (4, todas acessórias, na PR; 6 na RT; 5 na IN, uma principal e 4 acessórias). Todavia, apenas 26,7% (4/15) dessas mutações conferiam uma expressão fenotípica de resistência a uma das classes de inibidores (da RT ou IN), em 9,1% (4/44) dos indivíduos. Foi ainda observada uma elevada frequência de outros polimorfismos genéticos, mais frequentes em subtipos não-B, alguns dos quais considerados assinaturas de subtipo. A homologia genética total ou parcial com os subtipos B e G, reconhecida neste estudo, reflectirá a sua predominância na população de IDUs. Este resultado sugere também que a epidemia de HIV-1 em Portugal poderá estar a evoluir para um padrão epidemiológico singular, no qual os subtipos B, G e suas formas recombinantes predominam. A proporção observada de indivíduos portadores de vírus com mutações associadas a resistência, mesmo em indivíduos naive relativamente à terapêutica, indica que a sua transmissão se encontra em curso entre a população de IDUs, tendo, certamente, um impacto relevante ao nível da abordagem terapêutica e monitorização da infecção.
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Breast cancer is the most common cancer among women, being a major public health problem. Worldwide, X-ray mammography is the current gold-standard for medical imaging of breast cancer. However, it has associated some well-known limitations. The false-negative rates, up to 66% in symptomatic women, and the false-positive rates, up to 60%, are a continued source of concern and debate. These drawbacks prompt the development of other imaging techniques for breast cancer detection, in which Digital Breast Tomosynthesis (DBT) is included. DBT is a 3D radiographic technique that reduces the obscuring effect of tissue overlap and appears to address both issues of false-negative and false-positive rates. The 3D images in DBT are only achieved through image reconstruction methods. These methods play an important role in a clinical setting since there is a need to implement a reconstruction process that is both accurate and fast. This dissertation deals with the optimization of iterative algorithms, with parallel computing through an implementation on Graphics Processing Units (GPUs) to make the 3D reconstruction faster using Compute Unified Device Architecture (CUDA). Iterative algorithms have shown to produce the highest quality DBT images, but since they are computationally intensive, their clinical use is currently rejected. These algorithms have the potential to reduce patient dose in DBT scans. A method of integrating CUDA in Interactive Data Language (IDL) is proposed in order to accelerate the DBT image reconstructions. This method has never been attempted before for DBT. In this work the system matrix calculation, the most computationally expensive part of iterative algorithms, is accelerated. A speedup of 1.6 is achieved proving the fact that GPUs can accelerate the IDL implementation.
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Background: Thin melanomas (Breslow thickness <= 1 mm) are considered highly curable. The aim of this study was to evaluate the correlation between histological tumour regression and sentinel lymph node (SLN) involvement in thin melanomas. Patients and methods: This was a retrospective single-centre study of 34 patients with thin melanomas undergoing SLN biopsy between April 1998 and January 2005. Results: The study included 14 women and 20 men of mean age 56.3 years. Melanomas were located on the neck (n = 3), soles (n = 4), trunk (n = 13) and extremities (n = 14). Pathological examination showed 25 SSM, four acral lentiginous melanomas, three in situ melanomas, one nodular melanoma and one unclassified melanoma with a mean Breslow thickness of 0.57 mm. Histological tumour regression was observed in 26 over 34 cases and ulceration was found in one case. Clark levels were as follows: I (n = 3), II (n = 20), III (n = 9), IV (n = 2). Growth phase was available in 15 cases (seven radial and eight vertical). Mitotic rates, available in 24 cases, were: 0 (n = 9), 1 (n = 11), 2 (n = 2), 3 (n = 1), 6 (n = 1). One patient with histological tumour regression (2.9% of cases and 3.8% of cases with regressing tumours) had a metastatic SLN. One patient negative for SLN had a lung relapse and died of the disease. Mean follow-up was 26.2 months. Conclusion: The results of the present study and the analysis of the literature show that histological regression of the primary tumour does not seem predictive of higher risk of SLN involvement in thin melanomas. This suggests that screening for SLN is not indicated in thin melanomas, even those with histological regression.
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In this study, we evaluated the hepatitis B virus (HBV) genotype distribution and HBV genomic mutations among a group of human immunodeficiency virus-HBV co-infected patients from an AIDS outpatient clinic in São Paulo. HBV serological markers were detected by commercially available enzyme immunoassay kits. HBV DNA was detected using in-house nested polymerase chain reaction and quantified by Cobas Amplicor. HBV genotypes and mutations in the basal core promoter (BCP)/pre-core/core regions and surface/polymerase genes were determined by sequencing. Among the 59 patients included in this study, 55 reported prior use of lamivudine (LAM) or tenofovir. HBV DNA was detected in 16/22 patients, with a genotype distribution of A (n = 12,75%), G (n = 2,13%), D (n = 1,6%) and F (n = 1,6%). The sequence data of the two patients infected with genotype G strongly suggested co-infection with genotype A. In 10 patients with viremia, LAM-resistance mutations in the polymerase gene (rtL180M + rtM204V and rtV173L + rtL180M + rtM204V) were found, accompanied by changes in the envelope gene (sI195M, sW196L and sI195M/sE164D). Mutations in the BCP and pre-core regions were identified in four patients. In conclusion, genotype G, which is rarely seen in Brazil, was observed in the group of patients included in our study. A high prevalence of mutations associated with LAM-resistance and mutations associated with anti-HBs resistance were also found among these patients.
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Six patients, five of whom had normal and one impaired renal function, and all suffering from purulent arthritis caused by cephalosporin-sensitive germs, were given a seven-day course of 8 g cephacetrile daily. On the first day, 6 g were administered by continuous intravenous infusion at the rate of 500 mg/h, followed by 2 g over a further 45 min. On days 2 to 7, the patients received 2 short infusions of 4 g each at an interval of 12 h. In four patients with normal renal function, serum half-life ranged from 0.8 to 1.4 h, serum levels during continuous infusion from 19 to 31 microgram/ml, and total clearances from 265 to 434 ml/min. In one patients, these values were 1.6 h, 70 microgram/ml and 131 ml/min respectively (small volume of distribution). The concentrations in the synovial fluid varied from 2 to 29 mcirogram/ml; they were generally lower than the serum levels, but clearly exceeded the minimum inhibitory concentrations for germs commonly present in purulent arthritis. In five patients, the synovial fluid became germ-free and the arthritis was clinically cured. In the case presenting with renal insufficiency, the serum half-life was 5.8 h. During continuous administration, a steady state was not attained; peak serum levels amo9nted to 75 microgram/ml and the total clearance to 61 ml/min. The cephacetrile concentrations in the synovial fluid were very high (26 and 67 microgram/ml). In this case, in which the renal insufficiency associated with mycosis fungoides was present before the treatment, renal function deteriorated futher during treatment while the arthritis improved.
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Background: CYP2D6 is the key enzyme responsible for tamoxifen bioactivation mainly into endoxifen. This gene is highly polymorphic and breast cancer patients classified as CYP2D6 poor metabolizers (PM) or intermediate metabolizers (IM) appear to show low concentrations of endoxifen and to achieve less benefit from tamoxifen treatment. Purpose: This prospective, open-label trial aimed to assess how the increase of tamoxifen dose influences the level of endoxifen in the different genotype groups (poor-, intermediate-, and extensive-metabolizers (EM)). We examined the impact of doubling tamoxifen dose to 20mg twice daily on endoxifen plasma concentrations across these genotype groups. Patients and methods: Patients were assayed for CYP2D6 genotype and phenotype using dextromethorphan test. Tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen plasma levels were determined on 2 occasions at baseline (20mg/day of tamoxifen) and at day 30, 90 and 120 after dose increase (20 mg twice daily) using liquid chromatography-tandem-mass spectrometry. Endoxifen plasma levels were measured 6 to 24 hours after last drug intake to evaluate its accumulation before and after doubling tamoxifen dosage. ANOVA was used to evaluate endoxifen levels increase and difference between genotype groups. Results: 63 patients are available for analysis to date. Tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen plasma reached steady state at 30 day after tamoxifen dose escalation, with a significant increase compared to baseline by 1.6 to 1.8 fold : geometric mean plasma concentrations (CV %) were 140 ng/mL (45%) at baseline vs 255 (47%) at day 30 for tamoxifen (P < 0.0001); 256 (49%) vs 408 (64%) for N-desmethyltamoxifen (P < 0.0001); 2.4 (46%) vs 3.9 (51%) for 4-OH-tamoxifen (P < 0.0001); and 20 (91%) vs 33 (91%) for endoxifen (P < 0.02). On baseline, endoxifen levels tended to be lower in PM: 7 ng/mL (36%), than IM: 16 ng/mL (70%), P=0.08, and EM: 24 ng/mL (71%), P<0.001. After doubling tamoxifen dosage, endoxifen concentrations rose similarly in PM, IM and EM with respectively, 1.5 (18%), 1.5 (28%) and 1.7 (30%) fold increase from baseline, P=0.18. Conclusion: Endoxifen exposure varies widely under standard tamoxifen dosage, with CYP2D6 genotype explaining only a minor part of this variability. It increases consistently on doubling tamoxifen dose, similarly across genotypes. This would enable exposure optimization based on concentration monitoring.
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O diagnóstico sorológico da infecção pelo HIV-1 e HIV-2 teve início em Cabo Verde em 1987, mas pouco se sabe a respeito da diversidade genética desses vírus nessas ilhas, localizadas na costa Ocidental Africana. Neste estudo, caracterizamos a epidemiologia molecular do HIV-1 e HIV-2 em Cabo Verde, analisamos a origem dos principais clados de HIV introduzidos no país e descrevemos a ocorrência de mutações de resistência aos antirretrovirais (DRM) em indivíduos virgens de tratamento (ARTn) e pacientes em tratamento (ARTexp) oriundos das diferentes ilhas. Amostras de sangue, dados sociodemográfico e clínico-laboratoriais foram obtidos de 221 indivíduos HIV positivos entre 2010-2011. As amostras foram sequenciadas na região da polimerase (1300 pares de bases) e análises filogenéticas e de bootscan foram realizadas para a subtipagem viral. Os algoritmos disponibilizados nos sites Stanford HIV Database e HIV-GRADE e.V. Algorithm Homepage foram utilizados para avaliar a existência de DRM em pacientes positivos para HIV-1 e HIV-2, respectivamente. Os estudos evolutivos e filogeográficos foram realizados através do programa BEAST. Entre os 221 pacientes analisados, sendo 169 (76,5%) HIV-1, 43 (19,5%) HIV-2 e 9 de (4,1%) co-infectados pelo HIV-1 e pelo HIV-2, 67% eram do sexo feminino. As medianas de idade foram de 34 (IQR = 1-75) e 47 (IQR = 12-84) para o HIV-1 e HIV-2, respectivamente. A infecção pelo HIV-1 é causada pelo subtipo G (36,6%), CRF02_AG (30,6%), subtipo F1, (9,7%), URFs (10,4%), subtipo B (5,2%), CRF05_DF (3,0%), subtipo C (2,2%), CRF06_cpx (0,7%), CRF25_cpx (0,7%) e CRF49_cpx (0,7%), e todas as infecções por HIV-2 pertencem ao grupo A. De acordo com as análises filogeográficas e de origem do HIV, estima-se que o HIV-2 foi o primeiro tipo viral introduzido em Cabo Verde e possui relações filogenéticas com sequências referências de Portugal. O HIV-1 entrou no país mais tarde, primeiramente pelo subtipo G, evidenciando relações com sequências da África Central e de Portugal. Transmissão de DRM (TDRM) foi observada em 3,4% (2/58) de pacientes HIV-1 ARTn (1,7% NRTI, NNRTI 1,7%), mas não entre os infectados com HIV-2. Entre os pacientes ARTexp, DRM foi observada em 47,8% (33/69) dos infectados pelo HIV-1 (37,7% NRTI, NNRTI 37,7%, 7,4% de PI, 33,3% para duas classes) e 17,6% (3/17) nos infectados pelo HIV-2 (17,6%, 11,8% NRTI PI, 11,8% para ambas as classes). Este estudo indica que Cabo Verde tem um cenário epidemiológico molecular complexo e único dominado pelo HIV-1 subtipo G, CRF02_AG e F1 e HIV-2 grupo A, sendo esse o primeiro tipo viral introduzido em Cabo Verde. A ocorrência de TDRM e o nível relativamente elevado de DRM entre os pacientes tratados constituem uma preocupação, pelo que o monitoramento contínuo dos pacientes em ARTexp, incluindo genotipagem são políticas públicas a serem implementadas.
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Energy metabolism supports both inhibitory and excitatory neurotransmission processes. This study investigated the specific contribution of astrocytic metabolism to γ-aminobutyric acid (GABA) synthesis and inhibitory GABAergic neurotransmission that remained to be ilucidated in vivo. Therefore, we measured (13) C incorporation into brain metabolites by dynamic (13) C nuclear magnetic resonance spectroscopy at 14.1 T in rats under α-chloralose anaesthesia during infusion of [1,6-(13) C]glucose. The enhanced sensitivity at 14.1 T allowed to quantify incorporation of (13) C into the three aliphatic carbons of GABA non-invasively. Metabolic fluxes were determined with a mathematical model of brain metabolism comprising glial, glutamatergic and GABAergic compartments. GABA synthesis rate was 0.11 ± 0.01 μmol/g/min. GABA-glutamine cycle was 0.053 ± 0.003 μmol/g/min and accounted for 22 ± 1% of total neurotransmitter cycling between neurons and glia. Cerebral glucose oxidation was 0.47 ± 0.02 μmol/g/min, of which 35 ± 1% and 7 ± 1% was diverted to the glutamatergic and GABAergic tricarboxylic acid cycles, respectively. The remaining fraction of glucose oxidation was in glia, where 12 ± 1% of the TCA cycle flux was dedicated to oxidation of GABA. 16 ± 2% of glutamine synthesis was provided to GABAergic neurons. We conclude that substantial metabolic activity occurs in GABAergic neurons and that glial metabolism supports both glutamatergic and GABAergic neurons in the living rat brain. We performed (13) C NMR spectroscopy in vivo at high magnetic field (14.1 T) upon administration of [1,6-(13) C]glucose. This allowed to measure (13) C incorporation into the three aliphatic carbons of GABA in the rat brain, in addition to those of glutamate, glutamine and aspartate. These data were then modelled to determine fluxes of energy metabolism in GABAergic and glutamatergic neurons and glial cells.
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Fresh green bananas (Musa sp., subgroup Prata) were treated with a dose of only 90 ηg g-1 of 1-MCP for 13 hours and the evolution of the volatile compounds along the ripeness was studied. A method to quantify the emission of esters was developed by cryogenic headspace and gas chromatography. Esters of acetate, butyrate, isobutyrate and isovalerate were found as major compounds. The application of the 1-MCP for 13 hours delayed the appearance of the coloration 8 of the peel for 3 days and decreased quantitatively in about 46% the total production of esters in the banana until the 15° day of harvested.
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ABSTRACT Given the need to obtain systems to better control broiler production environment, we performed an experiment with broilers from 1 to 21 days, which were submitted to different intensities and air temperature durations in conditioned wind tunnels and the results were used for validation of afuzzy model. The model was developed using as input variables: duration of heat stress (days), dry bulb air temperature (°C) and as output variable: feed intake (g) weight gain (g) and feed conversion (g.g-1). The inference method used was Mamdani, 20 rules have been prepared and the defuzzification technique used was the Center of Gravity. A satisfactory efficiency in determining productive responses is evidenced in the results obtained in the model simulation, when compared with the experimental data, where R2 values calculated for feed intake, weight gain and feed conversion were 0.998, 0.981 and 0.980, respectively.
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To determine the influence of residual ß-cell function on retinopathy and microalbuminuria we measured basal C-peptide in 50 type 1 diabetic outpatients aged 24.96 ± 7.14 years, with a duration of diabetes of 9.1 ± 6.2 years. Forty-three patients (86%) with low C-peptide (<0.74 ng/ml) had longer duration of diabetes than 7 patients (14%) with high C-peptide (³0.74 ng/ml) (9 (2-34) vs 3 (1-10) years, P = 0.01) and a tendency to high glycated hemoglobin (HBA1) (8.8 (6-17.9) vs 7.7 (6.9-8.7)%, P = 0.08). Nine patients (18%) had microalbuminuria (two out of three overnight urine samples with an albumin excretion rate (AER) ³20 and <200 µg/min) and 13 (26%) had background retinopathy. No association was found between low C-peptide, microalbuminuria and retinopathy and no difference in basal C-peptide was observed between microalbuminuric and normoalbuminuric patients (0.4 ± 0.5 vs 0.19 ± 0.22 ng/ml, P = 0.61) and between patients with or without retinopathy (0.4 ± 0.6 vs 0.2 ± 0.3 ng/ml, P = 0.43). Multiple regression analysis showed that duration of diabetes (r = 0.30, r2 = 0.09, P = 0.031) followed by HBA1 (r = 0.41, r2 = 0.17, P = 0.01) influenced basal C-peptide, and this duration of diabetes was the only variable affecting AER (r = 0.40, r2 = 0.16, P = 0.004). In our sample of type 1 diabetic patients residual ß-cell function was not associated with microalbuminuria or retinopathy.
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In order to assess the molecular epidemiology of HIV-1 in two neighboring cities located near the epicenter of the HIV-1 epidemics in Brazil (Santos and São Paulo), we investigated 83 HIV-1 strains obtained from samples collected in 1995 from intravenous drug users. The V3 through V5 region of the envelope of gp 120 was analyzed by heteroduplex mobility analysis. Of the 95 samples, 12 (12.6%) were PCR negative (6 samples from each group); low DNA concentration was the reason for non-amplification in half of these cases. Of the 42 typed cases from São Paulo, 34 (81%, 95% confidence limits 74.9 to 87.0%) were B and 8 (19%, 95% confidence limits 12.9 to 25.0%) were F, whereas of the 41 typed cases from Santos, 39 (95%, 95% confidence limits 91.6 to 98.4%) were B and 2 (5%, 95% confidence limits 1.6 to 8.4%) were C. We therefore confirm the relationship between clade F and intravenous drug use in São Paulo, and the presence of clade C in Santos. The fact that different genetic subtypes of HIV-1 are co-circulating indicates a need for continuous surveillance for these subtypes as well as for recombinant viruses in Brazil.
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In a comparative study of erythrocyte metabolism of vertebrates, the specific activity of glucose-6-phosphate dehydrogenase (G6PD) of the Brazilian opossum Didelphis marsupialis in a hemolysate was shown to be high, 207 ± 38 IU g-1 Hb-1 min-1 at 37ºC, compared to the human erythrocyte activity of 12 ± 2 IU g-1 Hb-1 min-1 at 37ºC. The apparent high specific activity of the mixture led us to investigate the physicochemical properties of the opossum enzyme. We report that reduced glutathione (GSH) in the erythrocytes was only 50% higher than in human erythrocytes, a value lower than expected from the high G6PD activity since GSH is maintained in a reduced state by G6PD activity. The molecular mass, determined by G-200 Sephadex column chromatography at pH 8.0, was 265 kDa, which is essentially the same as that of human G6PD (260 kDa). The Michaelis-Menten constants (Km: 55 µM) for glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (Km: 3.3 µM) were similar to those of the human enzyme (Km: 50-70 and Km: 2.9-4.4, respectively). A 450-fold purification of the opossum enzyme was achieved and the specific activity of the purified enzyme, 90 IU/mg protein, was actually lower than the 150 IU/mg protein observed for human G6PD. We conclude that G6PD after purification from the hemolysate of D. marsupialis does not have a high specific activity. Thus, it is quite probable that the red cell hyperactivity reported may be explained by increased synthesis of G6PD molecules per unit of hemoglobin or to reduced inactivation in the RBC hemolysate.