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OBJECTIVE: One-third of patients newly diagnosed with a kidney tumor have metachoronous disease, 25-50% have synchronous metastasis, and approximately 30-40% of patients have metastasis at the time of diagnosis. Metastasis mostly occurs in the lungs, regional lymph nodes, bones, and liver. The present study was aimed to determine the effect on mortality the values of standard uptake value (SUV)max measured with positron emission tomography (PET) in metastases of kidney tumors. MATERIAL AND METHODS: A retrospective review was conducted of the files of 77 patients newly diagnosed with kidney tumor and disease staging determined with PET in the Nuclear medicine Department of Saglik Bilimleri University Diyarbakir Gazi Yasargil Training and Research Hospital between August 2007 and April 2012. The gender, age, histological types, metastases, SUVmax values, and dates of death of the patients were recorded in the SPSS software. RESULTS: It was observed that higher SUVmax values indicated a shorter survival time (r = .303) (P = 0.022). Patients with metastasis lived for a shorter period (P < 0.001), particularly those with liver metastasis (r = .515) (P = 0.049). Metastases were most frequently seen in lymph nodes (42.1%); the SUVmax values of lung metastases were higher (P = 0.025) and papillary carcinomas showed higher SUVmax uptake (P = 0.015). CONCLUSIONS: In the present study, it was concluded that the higher the SUVmax value the shorter the survival time. The survival time of patients with metastasis was shorter, and this could be estimated through the measured SUVmax values.
Assuntos
Carcinoma de Células Renais/diagnóstico , Fluordesoxiglucose F18/administração & dosagem , Neoplasias Renais/diagnóstico , Linfonodos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Neoplasias Pulmonares/diagnóstico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Período Pós-Operatório , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sensibilidade e Especificidade , Carga TumoralRESUMO
Objective.Electrical impedance tomography (EIT) is a noninvasive imaging method whereby electrical measurements on the periphery of a heterogeneous conductor are inverted to map its internal conductivity. The EIT method proposed here aims to improve computational speed and noise tolerance by introducing sensitivity volume as a figure-of-merit for comparing EIT measurement protocols.Approach.Each measurement is shown to correspond to a sensitivity vector in model space, such that the set of measurements, in turn, corresponds to a set of vectors that subtend a sensitivity volume in model space. A maximal sensitivity volume identifies the measurement protocol with the greatest sensitivity and greatest mutual orthogonality. A distinguishability criterion is generalized to quantify the increased noise tolerance of high sensitivity measurements.Main result.The sensitivity volume method allows the model space dimension to be minimized to match that of the data space, and the data importance to be increased within an expanded space of measurements defined by an increased number of contacts.Significance.The reduction in model space dimension is shown to increasecomputational efficiency, accelerating tomographic inversion by several orders of magnitude, while the enhanced sensitivitytolerates higher noiselevels up to several orders of magnitude larger than standard methods.
Assuntos
Algoritmos , Tomografia Computadorizada por Raios X , Impedância Elétrica , Tomografia/métodos , Condutividade ElétricaRESUMO
We report a case of antibody-mediated rejection treated with the human CD38 monoclonal antibody daratumumab in a 58-year-old female patient with end-stage kidney disease due to autosomal dominant polycystic kidney disease who received an ABO- and human leukocyte antigen antibody-incompatible living donor kidney transplant. The patient experienced an episode of severe antibody-mediated rejection within the first week of transplantation. Blood-group-antibody selective immunoadsorption in combination with administration of four doses of daratumumab (each 1800 mg s.c.) led to a persistent decrease of ABO- and more interestingly donor-specific human leukocyte antigen antibody reactivity and resulted in clinical and histopathological remission with full recovery of graft function, which has remained stable until post-transplant day 212. This case illustrates the potential of targeting CD38 in antibody-mediated rejection.
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PURPOSE: With arterial hypertension as a global risk factor for cerebrovascular and cardiovascular diseases, we examined whether retinal blood vessel caliber and tortuosity assessed by a vessel-constraint network model can predict the incidence of hypertension. METHODS: The community-based prospective study included 9230 individuals who were followed for 5 years. Ocular fundus photographs taken at baseline were analyzed by a vessel-constraint network model. RESULTS: Within the 5-year follow-up, 1279 (18.8%) and 474 (7.0%) participants out of 6813 individuals free of hypertension at baseline developed hypertension and severe hypertension, respectively. In multivariable analysis, a higher incidence of hypertension was related to a narrower retinal arteriolar diameter ( P â<â0.001), wider venular diameter ( P â=â0.005), and a smaller arteriole-to-venule diameter ratio ( P â<â0.001) at baseline. Individuals with the 5% narrowest arteriole or the 5% widest venule diameter had a 17.1-fold [95% confidence interval (CI):7.9, 37.2] or 2.3-fold (95% CI: 1.4, 3.7) increased risk for developing hypertension, as compared with those with the 5% widest arteriole or the 5% narrowest venule. The area under the receiver operator characteristic curve for predicting the 5-year incidence of hypertension and severe hypertension was 0.791 (95% CI: 0.778, 0.804) and 0.839 (95% CI: 0.821, 0.856), respectively. Although the venular tortuosity was positively associated with the presence of hypertension at baseline ( P â=â0.01), neither arteriolar tortuosity nor venular tortuosity was associated with incident hypertension (both P â≥â0.10). CONCLUSION AND RELEVANCE: Narrower retinal arterioles and wider venules indicate an increased risk for incident hypertension within 5 years, while tortuous retinal venules are associated with the presence rather than the incidence of hypertension. The automatic assessment of retinal vessel features performed well in identifying individuals at risk of developing hypertension.
Assuntos
Doenças Cardiovasculares , Hipertensão , Humanos , Estudos Prospectivos , Incidência , Vasos Retinianos/diagnóstico por imagem , Hipertensão/epidemiologia , Fatores de Risco , Arteríolas , VênulasRESUMO
PURPOSE: To predict the invasiveness of urothelial bladder carcinoma using a logistic regression model on preoperative peripheral blood samples. PATIENTS AND METHODS: Hospital data of patients operated for urothelial carcinoma were reviewed retrospectively. Preoperative blood samples were collected before the first cystoscopic examination. Any kind of infection or inflammation was an exclusion criterion. Patients were grouped as having a non-muscle-invasive or muscle-invasive urothelial carcinoma. The mean age was 69 years and was determined as the cut-off value. According to receiver operating characteristic curves, threshold points were determined for lymphocytes, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), thrombocytes and mean platelet volume. Demographic specialties, parameters obtained from blood samples, tumor size and multiplicity were evaluated and significant parameters were put into a logistic regression model. RESULTS: The study group consisted of 80 non-muscle-invasive and 102 muscle-invasive patients. Age (≤69 vs. >69), female gender, NLR (2.57), mean platelet volume (7.9/fl) and platelet count (400,000/µl) were significant parameters and put in a model. Using odds ratios, the probability of tumor invasiveness was calculated by a formula. CONCLUSION: Age, female gender, NLR and platelet count were found to be the predictors of invasiveness of urothelial carcinoma.
Assuntos
Carcinoma de Células de Transição/sangue , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/patologia , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Invasividade Neoplásica , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
The study was aimed to investigate the association between the degree of oligozoospermia and sperm chromosome aneuploidy frequencies in male infertility and to determine whether chromosomal profiles of sperm nuclei would be used for a supportive test before additive reproduction technics. The meiotic segregation profiles of chromosomes X, Y, 13, 18 and 21 were compared by fluorescent in-situ hybridisation (FISH) on the spermatozoa of 30 normally karyotyped oligozoospermic (10 mild, 11 moderate, nine severe) cases without Y-microdeletions, and 10 normozoospermic cases. The results showed significantly higher frequencies of chromosomes 13, 18, 21 disomies (P < 0.001) in the group of patients with moderate and severe oligozoospermia compared with the disomy frequencies of normozoospermic group. The statistically significant differences were also determined in disomy frequencies of sex chromosomes (XY, XX and YY) in between oligozoospermic and normozoospermic groups (P < 0.001, P < 0.001, P < 0.040, respectively). Because oligozoospermic patients are the ones consulted the most for assisted reproductive techniques, identification of sperm aneuploidy rates in men could be considered as an appropriate supportive test before the reproductive implementations. Furthermore, the patients should be counselled with respect to genetic screening results for the potential risk of aneuploid embryo and pre-implantation genetic diagnosis or prenatal diagnosis.
Assuntos
Aneuploidia , Oligospermia/genética , Oligospermia/patologia , Espermatozoides/patologia , Adulto , Estudos de Casos e Controles , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 21/genética , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Diploide , Humanos , Hibridização in Situ Fluorescente , Masculino , Oligospermia/terapia , Técnicas de Reprodução AssistidaRESUMO
Objective: To examine the survival rates and clinical characteristics of people with newly discovered non-M(3) acute myeloid leukemia (AML) who carry the ASXL1 gene mutation. Methods: From January 2016 to April 2021, the clinical information of patients with newly diagnosed non-M(3) AML at Shandong University's Qilu Hospital was retrospectively examined, and their clinical characteristics and survival were compared and analyzed. Gene mutation was detected by next-generation sequencing. Results: â The study included 256 AML patients who were initially diagnosed and had complete data, including 47 cases of ASXL1 gene mutation-positive (ASXL1(+)) patients and 209 cases of ASXL1 gene mutation-negative (ASXL1(-)) patients. All patients were divided into three groups: elderly (≥60 years old, n=92) , middle-aged (45-59 years old, n=92) , and young (≤44 years old, n=72) . â¡WBC, and age were higher in patients with ASXL1 mutations compared to ASXL1(-) patients, while complete response after the first round of treatment (CR(1)) was lower (P<0.05) . In the elderly group, WBC and the proportion of aberrant cells in nuclear cells in ASXL1(+) patients were higher than those in ASXL1(-) patients (P<0.05) . In the young group, the WBC of ASXL1(+) patients was higher than that of ASXL1(-) patients (z=-2.314, P=0.021) . â¢IDH2 mutation and ASXL1 mutation was related (P=0.018, r=0.34) . In ASXL1(+) patients, the proportion of peripheral blasts in the high VAF group (VAF>40% ) was higher than that in the low VAF group (VAF<20% ) , and the proportion of aberrant nuclear cells was higher in the duplication and replacement mutation patients than in the deletion mutation patients (P<0.05) . â£The overall survival (OS) and progression-free survival (PFS) of ASXL1(+) patients were shorter than those of ASXL1(-) patients (median, 10 months vs 20 months, 10 months vs 17 months; P<0.05) . The proportion number of aberrant cells in nuclear cells (≥20% ) , complex karyotypes, and TET2 mutation were all independent risk variables that had an impact on the prognosis of ASXL1(+) patients, according to multivariate analysis (P<0.05) . Conclusion: ASXL1-mutated non-M(3) AML patients have higher WBC in peripheral blood, a higher proportion of aberrant cells in nuclear cells, lower CR(1) rate, and shorter OS and PFS. Additionally, a poor prognosis is linked to higher VAF, duplication, and substitution mutations in the ASXL1 gene, as well as the high proportion of aberrant cells in nuclear cells, complex karyotype, and TET2 mutation.
Assuntos
Leucemia Mieloide Aguda , Nucleofosmina , Idoso , Pessoa de Meia-Idade , Humanos , Adulto , Estudos Retrospectivos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Análise de Sobrevida , Prognóstico , Fatores de Transcrição/genética , Fatores de Transcrição/uso terapêutico , Mutação , Proteínas Repressoras/genética , Proteínas Repressoras/uso terapêuticoRESUMO
PURPOSE: We validated the PADUA classification and assessed the R.E.N.A.L. nephrometry score to predict perioperative complications of partial nephrectomy. In addition, we assessed their interobserver variability, and the ability to predict the use of ischemia and ischemia time. MATERIALS AND METHODS: Data from consecutive cases of partial nephrectomy with or without ischemia from 3 centers were retrospectively collected. Associations between preoperative variables and complications were evaluated in univariate and multivariate analyses. Reproducibility was assessed by determining Fleiss' generalized kappa and intraclass correlation coefficients in a subcohort scored by 3 physicians with different degrees of urological expertise. RESULTS: A total of 134 partial nephrectomies were included in the study and 31 cases (23%) presented with complications. On univariate analyses complications were associated with age (p = 0.02), tumor size on computerized tomography (p = 0.01), pT stage (p = 0.001), and PADUA (p = 0.001) and R.E.N.A.L. scores (p = 0.02). In 3 multivariate models PADUA score 10 or greater (OR 3.98, p = 0.01), R.E.N.A.L. score 9 or greater (OR 4.21, p = 0.02), tumor size in cm (OR 1.35, p = 0.02) and age (OR 1.04, p = 0.04) were independent predictors of complications. The R.E.N.A.L. nephrometry score predicted the use of ischemia (p = 0.03) and both scores predicted ischemia time (both p <0.001). Kappa was 0.37 to 0.80 for PADUA components and 0.23 to 0.73 for R.E.N.A.L. components. The intraclass correlation coefficient was 0.73 for PADUA and 0.70 for R.E.N.A.L. score. CONCLUSIONS: The highest categories of PADUA and R.E.N.A.L. scores as well as clinical tumor size predict the risk of perioperative complications of partial nephrectomy. Both scores can indicate ischemia time. Their reproducibility is substantial but the implementation of these systems in clinical practice needs further refinement.
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Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/patologia , Neoplasias Renais/classificação , Neoplasias Renais/patologia , Nefrectomia/métodos , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/cirurgia , Estadiamento de Neoplasias , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de RiscoRESUMO
The evaluation of interactions between drug candidates and transporters such as P-glycoprotein (P-gp) has gained considerable interest in drug discovery and development. Inhibition of P-gp can be assessed by performing bi-directional permeability studies with in vitro P-gp-expressing cellular model systems such as Caco-2 (human colon carcinoma) cells, using digoxin as a substrate probe. Existing methodologies include either assaying (3)H-digoxin with liquid scintillation counting (LSC) detection or assaying non-labeled digoxin with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis at a speed of several minutes per sample. However, it is not feasible to achieve a throughput high enough using these approaches to sustain an early liability screen that generates more than a thousand samples on a daily basis. To address this challenge, we developed an ultrafast (9 s per sample) bioanalytical method for digoxin analysis using RapidFire™, an on-line solid-phase extraction (SPE) system, with MS/MS detection. A stable isotope labeled analog, d3-digoxin, was used as internal standard to minimize potential ionization matrix effect during the RF-MS/MS analysis. The RF-MS/MS method was more than 16 times faster than the LC-MS/MS method but demonstrated similar sensitivity, selectivity, reproducibility, linearity and robustness. P-gp inhibition results of multiple validation compounds obtained with this RF-MS/MS method were in agreement with those generated by both the LC-MS/MS method and the (3)H-radiolabel assay. This method has been successfully deployed to assess P-gp inhibition potential as an important early liability screen for drug-transporter interaction.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Cromatografia Líquida/métodos , Digoxina/análise , Ensaios de Triagem em Larga Escala/métodos , Espectrometria de Massas em Tandem/métodos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Células CACO-2 , Ciclosporina/química , Ciclosporina/farmacologia , Digoxina/química , Digoxina/metabolismo , Descoberta de Drogas/métodos , Descoberta de Drogas/normas , Humanos , Modelos Lineares , Modelos Biológicos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Extração em Fase Sólida , TrítioRESUMO
AIM OF THE STUDY: The purpose of the study was to determine the aeroallergen sensitisation patterns of children aged 5 years and younger with asthma (AS) and/or allergic rhinitis (AR) in Istanbul, Turkey. METHODS: This cross-sectional observational study was conducted between January and December 2018 in the outpatient clinic of a hospital department of pediatric allergy. Patients, who had regular outpatient controls, full clinical and laboratory records, positive skin prick test results, and were willing to participate in the study, were included. RESULTS: In total, 148 children aged 5 years or younger who had positive skin prick test results were included in the study. The male/female ratio and the mean age at onset of symptoms were 87/61 and 2.13±1.33 (0.4-4.5) years, respectively. Of the 148 patients, 63 (42.6%) had AS, 11 (7.4%) AR, and 74 (50.0%) had both AS and AR. The age of the patients, age at symptom onset, male/female ratio, number of allergen sensitivities, total IgE levels, total eosinophil levels, and skin prick test results for aeroallergens did not differ between the patients with AS, AR, and AS+AR. House dust mite (HDM) was the most common aeroallergen in patients, while the cockroach was the least common aeroallergen. The severity of asthma and control levels were not found to be associated with aeroallergen sensitisation in children. CONCLUSION: One out of every four atopic children aged 5 years or younger is sensitised to aeroallergens. The most common sensitisation is to house dust mites. Weed aeroallergen may be related to severity of asthma in children aged 5 years or younger in Istanbul. We speculate that HDM and weed allergens could be used in the diagnostic or treatment strategies for the management of asthmatic children aged 5 years or younger.
Assuntos
Alérgenos/efeitos adversos , Asma/etiologia , Rinite Alérgica/etiologia , Alérgenos/imunologia , Asma/diagnóstico , Asma/imunologia , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Fatores de Risco , Índice de Gravidade de Doença , Testes Cutâneos , TurquiaRESUMO
OBJECTIVE: This study aimed to determine the prognostic role of baseline maximum standardized uptake value (SUVmax) obtained by pretreatment PET/CT and the change in SUVmax (ΔSUVmax [%]) in patients with axillary lymph node-positive breast cancer receiving neoadjuvant chemotherapy (NAC). METHODS: One hundred and eighty patients with baseline SUVmax and 121 patients with SUVmax measurement after treatment were evaluated in the study. The baseline SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAI) and the change in the SUVmax of the breast (ΔSUVmaxB) and axilla (ΔSUVmaxA) were measured. The optimal cut-off value of SUVmax and ΔSUVmax were determined by ROC curve analysis. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier curves. RESULTS: ΔSUVmaxB, pCRB, pCRA, and pCR parameters were found to be associated with relapse (p < 0.001, p = 0.033, p = 0.016, and p = 0.013, respectively). ΔSUVmaxB and SUVmaxAI were associated with mortality (p = 0.001 and p = 0.006, respectively). Multiple Cox regression analyses revealed that ΔSUVmaxB value was an independent prognostic factor for relapse and mortality (p = 0.013 and p = 0.010, respectively). CONCLUSION: The results showed that ΔSUVmaxB was an independent prognostic factor for relapse and mortality in patients with axillary lymph node-positive breast cancer who received NAC.
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Structural prosthetic valve deterioration and nonstructural dysfunction are two common causes of nonfatal valve events following implantation of a bioprosthetic valve. Using caution and skill, implantation of a bioprosthesis is relatively easy. On the other hand, explantation of a bioprosthesis is a challenging and time-consuming procedure. We have developed a surgical technique by which we were able to ameliorate this troublesome situation in a 79-year-old man with aortic stenosis in whom we had to intraoperatively explant the bioprosthesis that we have put in initially. Another bioprosthesis of the same kind was used to replace the old prosthesis with the rest of his postoperative course until dismissal being eventless.
Assuntos
Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/patologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/patologia , Fibrilação Atrial , Cardiomiopatias , Ecocardiografia Transesofagiana , Humanos , Período Intraoperatório , Masculino , Isquemia Miocárdica , Volume Sistólico , Sístole , Função Ventricular EsquerdaAssuntos
Antibacterianos/efeitos adversos , Cefixima/efeitos adversos , Claritromicina/efeitos adversos , Toxidermias/etiologia , Antifúngicos/efeitos adversos , Pré-Escolar , Ciclopirox , Toxidermias/patologia , Hipersensibilidade a Drogas , Humanos , Masculino , Miconazol/efeitos adversos , Miconazol/análogos & derivados , Otite Média/tratamento farmacológico , Piridonas/efeitos adversos , Tinha/tratamento farmacológicoRESUMO
Small molecule high-throughput screening in drug discovery today is dominated by techniques which are dependent upon artificial labels or reporter systems. While effective, these approaches can be affected by certain experimental limitations, such as conformational restrictions imposed by the selected label or compound fluorescence/quenching. Label-free approaches potentially address many of these issues by allowing researchers to investigate more native systems without fluorescence- or luminescence-based readouts. However, due to throughput and expense constraints, label-free methods have been largely relegated to a supporting role as the basis of secondary assays. In this review, we describe recent improvements in impedance-based, optical biosensor-based, automated patch clamp and mass spectrometry technologies that have enhanced their ease of use and throughput and, hence, their utility for primary screening of small- to medium-sized compound libraries. The ultimate maturation of these techniques will enable drug discovery researchers to screen large chemical libraries against minimally manipulated biological systems.
Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Bibliotecas de Moléculas Pequenas , Animais , Avaliação Pré-Clínica de Medicamentos/instrumentação , Impedância Elétrica , Humanos , Espectrometria de Massas/instrumentação , Espectrometria de Massas/métodos , Técnicas de Patch-Clamp/instrumentação , Técnicas de Patch-Clamp/métodos , Espectrofotometria/instrumentação , Espectrofotometria/métodos , Ressonância de Plasmônio de Superfície/instrumentação , Ressonância de Plasmônio de Superfície/métodosRESUMO
OBJECTIVES: Elevation of serum total homocysteine (tHcy) is considered to contribute to endothelial cell dysfunction, which is considered to be the initial event in posttransplant vascular disease. We sought to investigate whether an association existed between serum tHcy levels and vascular endothelial function during cyclosporine (CsA) treatment. MATERIALS AND METHODS: Endothelium-dependent and -independent relaxation responses (to acetylcholine [ACh] and sodium nitroprusside [SNP]) were determined on thoracic aortae from CsA-treated rats (5 mg kg/d, subcutaneously, for 14 days). A correlation analysis was performed between ACh responses and tHcy levels. RESULTS: CsA decreased the responses to ACh and the pD(2) values of the concentration-response curves compared with controls (P < .05). Responses to SNP and serum tHcy levels were unchanged among the groups. tHcy negatively correlated with the ACh pD(2) values among control (r = -0.69; P < .05) and vehicle (r = -0.73; P < .05) groups, indicating that the increase in tHcy was associated with decreased sensitivity to ACh. In CsA-treated rats, no association was observed between these parameters. Also, no correlation was noted between CsA concentrations and tHcy levels. CONCLUSION: These data suggested a possible link between serum tHcy and decreased vascular sensitivity to endothelium-dependent vasorelaxation in control aortae, but CsA-induced vascular endothelial dysfunction was not associated with an effect of the drug on homocysteine metabolism.
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Aorta Torácica/fisiologia , Ciclosporina/farmacologia , Endotélio Vascular/fisiopatologia , Homocisteína/sangue , Animais , Aorta Torácica/efeitos dos fármacos , Ciclosporina/sangue , Emulsões/farmacologia , Endotélio Vascular/efeitos dos fármacos , Imunossupressores/farmacologia , Técnicas In Vitro , Masculino , Nitroprussiato/farmacologia , Polietilenoglicóis/farmacologia , Ratos , Ratos Wistar , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
Mass spectrometry is an emerging format for label-free high-throughput screening. The main limitation of mass spectrometry is throughput, due to the requirement to purify samples prior to ionization. Here the authors compare an automated high-throughput mass spectrometry (HTMS) system (RapidFire) with the scintillation proximity assay (SPA). The cancer therapy target AKT1/PKBalpha was screened against a focused library of kinase inhibitors and IC50 values determined for all compounds that exhibit > 50% inhibition. A selection of additional compounds that exhibited Assuntos
Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores
, Proteínas Proto-Oncogênicas c-akt/isolamento & purificação
, Contagem de Cintilação
, Espectrometria de Massas por Ionização por Electrospray
, Sequência de Aminoácidos
, Reações Falso-Negativas
, Reações Falso-Positivas
, Dados de Sequência Molecular
, Inibidores de Proteínas Quinases/farmacologia
, Proteínas Proto-Oncogênicas c-akt/química
RESUMO
A high-throughput mass spectrometry assay to measure the catalytic activity of phosphatidylserine decarboxylase (PISD) is described. PISD converts phosphatidylserine to phosphatidylethanolamine during lipid synthesis. Traditional methods of measuring PISD activity are low throughput and unsuitable for the high-throughput screening of large compound libraries. The high-throughput mass spectrometry assay directly measures phosphatidylserine and phosphatidylethanolamine using the RapidFiretrade mark platform at a rate of 1 sample every 7.5 s. The assay is robust, with an average Z' value of 0.79 from a screen of 9920 compounds. Of 60 compounds selected for confirmation, 54 are active in dose-response studies. The application of high-throughput mass spectrometry permitted a high-quality screen to be performed for an otherwise intractable target.
Assuntos
Carboxiliases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Espectrometria de Massas/métodos , Carboxiliases/análise , Carboxiliases/genética , Linhagem Celular , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Estabilidade Enzimática , Congelamento , Humanos , Rim/citologia , Cinética , Plasmídeos , Proteínas Recombinantes de Fusão/antagonistas & inibidores , Robótica , Análise de Sequência de DNA , TransfecçãoRESUMO
In July 2005, small (2 to 5 mm), elongated, dark brown spots on the stems of Cicer pinnatifidum Jaub. & Spach. were observed on plants grown in the rocky hills of the Kahramanmaras Province. To understand this phenomenon, field trips to Kahramanmaras, Adiyaman, and Sanliurfa provinces were conducted in the summer of 2006. C. pinnatifidum plants exhibiting symptoms similar to Ascochyta rabiei (Pass.) Lab. were collected during May and June. The plants had flowers and pods with seeds at the time of collection. Ascochyta blight symptoms on stems were not extensive. None of the plants had leaf symptoms, but one plant had lesions on its pods. Twelve plants exhibiting Ascochyta blight symptoms were taken to the laboratory, and necrotic parts were used for isolation of the fungi on potato dextrose agar (PDA). After 3 to 5 days of culturing on PDA, characteristic beige-to-dark brown colony development of A. rabiei from explants was observed and five isolates from different locations were recovered. The fungal colony growth was slow and limited conidia formed on PDA. The isolates were also cultured on chickpea meal agar (CMA) and Czapek Dox Agar (CDA) media. Abundant conidia formation occurred only on CMA, 10 to 12 days after culturing. Conidia were one-celled similar to that of A. rabiei of chickpea and single-spore isolations were done. C. pinnatifidum and chickpea cv. Gokce (C. arietinum L.) were inoculated with spore suspensions of 5 × 105 spores per ml (2). Ten- to twelve-day-old seedlings were used for inoculation in the experiments. Brown-black lesions at the crown region on C. pinnatifidum seedlings were observed 9 to 10 days after inoculation, and characteristic Ascochyta blight symptoms on stems developed on chickpea cv. Gokce. The fungus was reisolated from the infected seedlings. For molecular characterization, mating type of the isolates was determined by PCR using A. rabiei specific Tail1, Com1, and Sp21 primers (1). A single band of Mat 1.2 specific 500- bp product was amplified by PCR from five of the A. rabiei isolates of C. pinnatifidum. This confirmed that the isolates from C. pinnatifidum are A. rabiei. References: (1) M. P. Barve et al. Fungal Genet. Biol. 39:151, 2003. (2) M. S. A. Khan et al. Plant Pathol. 48:230, 1999.
RESUMO
Objetivo: En este estudio, se tuvo como objetivo determinar el papel pronóstico del valor de captación máximo estandarizado (SUVmáx) basal obtenido por PET/TC antes del tratamiento, y el cambio en el SUVmáx (ΔSUVmáx [%]) en pacientes con cáncer de mama con ganglios linfáticos axilares positivos en tratamiento con quimioterapia neoadyuvante (NAC).Métodos: Se evaluaron en el estudio 180 pacientes con SUVmáx basal y 121 pacientes con medición de SUVmáx después del tratamiento. Se midieron el valor de SUVmáx inicial de la mama (SUVmáxBI) y axila (SUVmáxAI), y el cambio en el SUVmáx de la mama (ΔSUVmáxB) y axila (ΔSUVmáxA). El valor de corte óptimo de SUVmáx y ΔSUVmáx se determinó mediante el análisis de la curva ROC. La supervivencia libre de enfermedad (SSE) y la supervivencia global (SG) se calcularon mediante curvas de Kaplan-Meier.Resultados: Se encontró que los parámetros ΔSUVmáxB, pCRB, pCRA y pCR se asociaron con la recaída (p <0.001, p =0.033, p =0.016 y p =0.013, respectivamente). ΔSUVmáxB y SUVmáxAI se asociaron con la mortalidad (p=0,001 y p=0,006, respectivamente). El análisis de regresión de Cox múltiple reveló que el valor de ΔSUVmáxB era un factor pronóstico independiente para la recaída y la mortalidad (p = 0,013 y p = 0,010, respectivamente).Conclusión: Los resultados muestran que ΔSUVmáxB es un factor pronóstico independiente de recaída y mortalidad en pacientes con cáncer de mama con ganglios linfáticos axilares positivos que recibieron NAC (AU)
Objective: This study aimed to determine the prognostic role of baseline maximum standardized uptake value (SUVmax) obtained by pretreatment PET/CT and the change in SUVmax (ΔSUVmax [%]) in patients with axillary lymph nodepositive breast cancer receiving neoadjuvant chemotherapy (NAC).Methods: One hundred and eighty patients with baseline SUVmax and 121 patients with SUVmax measurement after treatment were evaluated in the study. The baseline SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAI) and the change in the SUVmax of the breast (ΔSUVmaxB) and axilla (ΔSUVmaxA) were measured. The optimal cut-off value of SUVmax and ΔSUVmax were determined by ROC curve analysis. Disease-free survival (DFS) and overall survival (OS) were calculated using KaplanMeier curves.Results: ΔSUVmaxB, pCRB, pCRA, and pCR parameters were found to be associated with relapse (p < 0.001, p = 0.033, p = 0.016, and p = 0.013, respectively). ΔSUVmaxB and SUVmaxAI were associated with mortality (p = 0.001 and p = 0.006, respectively). Multiple Cox regression analyses revealed that ΔSUVmaxB value was an independent prognostic factor for relapse and mortality (p = 0.013 and p = 0.010, respectively).Conclusion: The results showed that ΔSUVmaxB was an independent prognostic factor for relapse and mortality in patients with axillary lymph nodepositive breast cancer who received NAC (AU)
Assuntos
Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Fluordesoxiglucose F18/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , PrognósticoRESUMO
OBJECTIVE: To assess the effects of smoking on total sperm count, progressive sperm motility and sperm morphology among couples attending an infertility clinic. METHODS: A total of 223 sperm samples (126 smokers and 97 nonsmokers) from men attending an infertility clinic for routine infertility workup were compared on the basis of standard semen analysis. RESULTS: Cigarette smoking is negatively correlated with progressive motile sperm count (r = -0.1464, p = 0.042), but not with sperm concentration (p = 0.961), total motile sperm count (p = 0.890) and sperm morphology (p = 0.838). Furthermore, packages/ year (cumulative dose of cigarettes) did not correlate with any of the sperm parameters including sperm density (p = 0.976), total (p = 0.559) and progressive (p = 0.406) motile sperm count and sperm morphology (p = 0.449). CONCLUSIONS: Although the effect of smoking on male infertility remains inconclusive, smoking had an adverse effect on the progressive sperm motility, irrespective of total amount of cigarettes smoked per day.