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In this study, S-methyl derivatives of dithiocarbamates (DTCs) were shown to significantly enhance chemiluminescence (CL) between Ce(IV) and efficient and environmentally friendly nitrogen-doped carbon dots (NCDs). Based on the elucidation of the CL mechanisms, an innovative approach involving high-performance liquid chromatography coupled with N-CDs and CL detection (HPLC-CDCL) was proposed. The developed method was successfully applied to the highly sensitive detection of three DTC fungicides (dimethyl dithiocarbamate, ethylene bisdithiocarbamate, and propylene bisdithiocarbamate) in tea. The recovery of the established method ranged 70.51-116.45%, with relative standard deviations (RSD) of <9.40%. The limit of detection (S/N = 3) was as low as 0.19 µg/L (as CS2), which is superior to the previous methods and comparable to UPLC-tandem mass spectrometry (MS/MS). Moreover, the proposed approach does not require solid-phase extraction and offers excellent selectivity. This study proposes a novel method for the detection of DTCs in the food safety and environmental fields.
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Carbono , Contaminação de Alimentos , Nitrogênio , Chá , Tiocarbamatos , Cromatografia Líquida de Alta Pressão/métodos , Chá/química , Tiocarbamatos/química , Tiocarbamatos/análise , Carbono/química , Contaminação de Alimentos/análise , Nitrogênio/química , Pontos Quânticos/química , Limite de Detecção , Fungicidas Industriais/análise , Fungicidas Industriais/químicaRESUMO
With neutron diffraction, the local stress and texture of metallic components can be analyzed non-destructively. For both, highly accurate positioning of the sample is essential, requiring the measurement at the same sample location from different directions. Current sample-positioning systems in neutron diffraction instruments combine XYZ tables and Eulerian cradles to enable the accurate six-degree-of-freedom (6DoF) handling of samples. However, these systems are not flexible enough. The choice of the rotation center and their range of motion are limited. Industrial six-axis robots have the necessary flexibility, but they lack the required absolute accuracy. This paper proposes a visual servoing system consisting of an industrial six-axis robot enhanced with a high-precision multi-camera tracking system. Its goal is to achieve an absolute positioning accuracy of better than 50µm. A digital twin integrates various data sources from the instrument and the sample in order to enable a fully automatic measurement procedure. This system is also highly relevant for other kinds of processes that require the accurate and flexible handling of objects and tools, e.g., robotic surgery or industrial printing on 3D surfaces.
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The strength-ductility trade-off has been a long-standing challenge when designing and fabricating a novel metal matrix composite. In this study, graphene-nanosheets (GNSs)-reinforced copper (Cu)-matrix-laminated composites were fabricated through two methods, i.e., the alternating electrodeposition technique followed by spark plasma sintering (SPS) and direct electrodeposition followed by hot-press sintering. As a result, a Cu-GNS-Cu layered structure formed in the composites with various Cu layer thicknesses. Compared with the pure Cu, the yield strength of the GNS/Cu composites increased. However, the mechanical performance of the GNS/Cu composites was strongly Cu-layer-thickness-dependent, and the GNS/Cu composite possessed a brittle fracture mode when the Cu layer was thin (≤10 µm). The fracture mechanism of the GNS/Cu composites was thoroughly investigated and the results showed that the premature failure of the GNS/Cu composites with a thin Cu layer may be due to the lack of Cu matrix, which can relax the excessive stress intensity triggered by GNSs and delay the crack connection between neighboring GNS layers. This study highlights the soft Cu matrix in balancing the strength and ductility of the GNS/Cu-laminated composites and provides new technical and theoretical support for the preparation and optimization of other laminated metal matrix composites.
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The effect of the heat treatment on the residual stresses of welded cladded steel samples is analyzed in this study. The residual stresses across the plate's square sections were determined using complementary methods; applying diffraction with neutron radiation and mechanically using the contour method. The analysis of the large coarse grain austenitic cladded layers, at the feasibility limits of diffraction methods, was only made possible by applying both methods. The samples are composed of steel plates, coated on one of the faces with stainless steel filler metals, this coating process, usually known as cladding, was carried out by submerged arc welding. After cladding, the samples were submitted to two different heat treatments with dissimilar parameters: one at a temperature of 620 °C maintained for 1 h and, the second at 540 °C, for ten hours. There was some difference in residual stresses measured by the two techniques along the surface of the coating in the as-welded state, although they are similar at the welding interface and in the heat-affected zone. The results also show that there is a residual stress relaxation for both heat-treated samples. The heat treatment carried out at a higher temperature showed sometimes more than 50% reduction in the initial residual stress values and has the advantage of being less time consuming, giving it an industrial advantage and making it more viable economically.
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The influence of amount of intermetallics on the degradation of as-extruded Mg-Nd alloys with different contents of Nd was investigated via immersion testing in DMEM+10% FBS under cell culture conditions and subsequent microstructural characterizations. It is found that the presence of intermetallic particles Mg41Nd5 affects the corrosion of Mg-Nd alloys in two conflicting ways. One is their negative role that their existence enhances the micro-galvanic corrosion. Another is their positive role. Their existence favours the formation of a continuous and compact corrosion layer. At the early stage of immersion, their negative role predominated. The degradation rate of Mg-Nd alloys monotonously increases with increasing the amount of intermetallics. Mg-5Nd alloy with maximum amount of intermetallics suffered from the most severe corrosion. With the immersion proceeding (≥7 days), then the positive role of these intermetallic particles Mg41Nd5 could not be neglected. Owing to the interaction between their positive and negative roles, at the later stage of immersion the corrosion rate of Mg-Nd alloys first increases with increasing the content of Nd, then reaches to the maximum at 2 wt. % Nd. With a further increase of Nd content, a decrease in corrosion rate occurs. The main corrosion products on the surfaces of Mg-Nd alloys include carbonates, calcium-phosphate, neodymium oxide and/or neodymium hydroxide. They are amorphous at the early stage of immersion. With the immersion proceeding, they are transformed to crystalline. The existence of undegradable Mg41Nd5 particles in the corrosion layer can enhance the crystallization of such amorphous corrosion products.
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Ligas , Magnésio , Corrosão , Teste de MateriaisRESUMO
Single-crystal elastic constants have been derived by lattice strain measurements using neutron diffraction on polycrystalline Ti-6Al-4V, Ti-6Al-2Sn-4Zr-6Mo and Ti-3Al-8V-6Cr-4Zr-4Mo alloy samples. A variety of model approximations for the grain-to-grain interactions, namely approaches by Voigt, Reuss, Hill, Kroener, de Wit and Matthies, including texture weightings, have been applied and compared. A load-transfer approach for multiphase alloys was also implemented and the results are compared with single-phase data. For the materials under investigation, the results for multiphase alloys agree well with the results for single-phase materials in the corresponding phases. In this respect, all eight elastic constants in the dual-phase Ti-6Al-2Sn-4Zr-6Mo alloy have been derived for the first time.
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OBJECTIVE: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. METHODS: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. RESULTS: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p < 0.001). The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7% and 89.6%, respectively (p = 0.004). The sensitivity values of FISH for low and high grade bladder cancer were 82.6% and 90.1%, respectively (p = 0.002). CONCLUSION: FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages. Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.
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Elastocaloric cooling is currently under extensive study owing to its great potential to replace the conventional vapor-compression technique. In this work, by employing multiscale characterization approaches, including in situ neutron diffraction in a loading frame, in situ transmission electron microscopy observation at different temperatures, in situ synchrotron X-ray Laue microdiffraction, and high-resolution infrared thermal imaging, we have investigated the thermal and stress-induced martensitic transformation, the stability of superelastic behavior and the associated elastocaloric effect for a Heusler-type Ni50.0Fe19.0Ga27.1Co3.9 single crystal. On the basis of transformation from cubic austenite into monoclinic martensite with a flexibly and reversibly transferring interface, this unique single crystal exhibits a giant elastocaloric effect of 11 K and ultralow fatigue behavior during above 12 000 mechanical cycles. The numerical simulation shows that the Ni50.0Fe19.0Ga27.1Co3.9 alloy offers 18% energy saving potential and 70% cooling capacity enhancement potential compared to the conventional shape-memory nitinol alloy in a single-stage elastocaloric cooling system, making it a great candidate for energy-efficient air conditioner applications.
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Drug dependence and withdrawal syndrome induced by abrupt cessation of opioid administration remain a severe obstacle in the clinical treatment of chronic pain and opioid drug addiction. One of the key symptoms during opioid withdrawal is hyperalgesia. The mechanism of opioid withdrawal-induced hyperalgesia remains unclear. P2X2 and P2X3 receptors, members of P2X receptor subunits, act as the integrator of multiple forms of noxious stimuli and play an important role in nociception transduction of chronic neuropathic and inflammatory pain. The process of P2X2 and P2X3 receptor antagonism inhibits inflammatory hyperalgesia, involving the spinal opioid system. However, the role of P2X receptors involved in opioid withdrawal-induced hyperalgesia has seldom been discussed. To explore the role of P2X2 and P2X3 receptors in the opioid-induced hyperalgesia, heroin self-administration rats were adopted, and the thermal and mechanical nociceptive thresholds were evaluated using the paw withdrawal test after abstinence from heroin for 8 days. In addition, the expressions of P2X2 and P2X3 receptors in dorsal root ganglia were analyzed by immunofluorescence. The results showed that after 8 days of abstinence, heroin self-administration rats showed thermal hyperalgesia and mechanical allodynia. Meanwhile, the expressions of the P2X2 and P2X3 receptors in dorsal root ganglia were increased. These results suggest that upregulation of P2X2 and P2X3 receptors might partially play a role in heroin withdrawal-induced hyperalgesia.
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Dependência de Heroína/metabolismo , Hiperalgesia/metabolismo , Receptores Purinérgicos P2X2/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Síndrome de Abstinência a Substâncias/metabolismo , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Animais , Modelos Animais de Doenças , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Heroína/administração & dosagem , Heroína/efeitos adversos , Temperatura Alta , Hiperalgesia/etiologia , Masculino , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Ratos Sprague-Dawley , Autoadministração , Tato , Regulação para CimaRESUMO
Heusler type Ni-Mn-Ga ferromagnetic shape memory alloys can demonstrate excellent magnetic shape memory effect in single crystals. However, such effect in polycrystalline alloys is greatly weakened due to the random distribution of crystallographic orientation. Microstructure optimization and texture control are of great significance and challenge to improve the functional behaviors of polycrystalline alloys. In this paper, we summarize our recent progress on the microstructure control in polycrystalline Ni-Mn-Ga alloys in the form of bulk alloys, melt-spun ribbons and thin films, based on the detailed crystallographic characterizations through neutron diffraction, X-ray diffraction and electron backscatter diffraction. The presented results are expected to offer some guidelines for the microstructure modification and functional performance control of ferromagnetic shape memory alloys.
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PURPOSE:: To evaluate whether low energy shock wave preconditioning could reduce renal ischemic reperfusion injury caused by renal artery occlusion. METHODS:: The right kidneys of 64 male Sprague Dawley rats were removed to establish an isolated kidney model. The rats were then divided into four treatment groups: Group 1 was the sham treatment group; Group 2, received only low-energy (12 kv, 1 Hz, 200 times) shock wave preconditioning; Group 3 received the same low-energy shock wave preconditioning as Group 2, and then the left renal artery was occluded for 45 minutes; and Group 4 had the left renal artery occluded for 45 minutes. At 24 hours and one-week time points after reperfusion, serum inducible nitric oxide synthase (iNOS), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), creatinine (Cr), and cystatin C (Cys C) levels were measured, malondialdehyde (MDA) in kidney tissue was detected, and changes in nephric morphology were evaluated by light and electron microscopy. RESULTS:: Twenty-four hours after reperfusion, serum iNOS, NGAL, Cr, Cys C, and MDA levels in Group 3 were significantly lower than those in Group 4; light and electron microscopy showed that the renal tissue injury in Group 3 was significantly lighter than that in Group 4. One week after reperfusion, serum NGAL, KIM-1, and Cys C levels in Group 3 were significantly lower than those in Group 4. CONCLUSION:: Low-energy shock wave preconditioning can reduce renal ischemic reperfusion injury caused by renal artery occlusion in an isolated kidney rat model.
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Precondicionamento Isquêmico/métodos , Rim/irrigação sanguínea , Obstrução da Artéria Renal/complicações , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/terapia , Terapia por Ondas Curtas/métodos , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Abstract Purpose: To evaluate whether low energy shock wave preconditioning could reduce renal ischemic reperfusion injury caused by renal artery occlusion. Methods: The right kidneys of 64 male Sprague Dawley rats were removed to establish an isolated kidney model. The rats were then divided into four treatment groups: Group 1 was the sham treatment group; Group 2, received only low-energy (12 kv, 1 Hz, 200 times) shock wave preconditioning; Group 3 received the same low-energy shock wave preconditioning as Group 2, and then the left renal artery was occluded for 45 minutes; and Group 4 had the left renal artery occluded for 45 minutes. At 24 hours and one-week time points after reperfusion, serum inducible nitric oxide synthase (iNOS), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), creatinine (Cr), and cystatin C (Cys C) levels were measured, malondialdehyde (MDA) in kidney tissue was detected, and changes in nephric morphology were evaluated by light and electron microscopy. Results: Twenty-four hours after reperfusion, serum iNOS, NGAL, Cr, Cys C, and MDA levels in Group 3 were significantly lower than those in Group 4; light and electron microscopy showed that the renal tissue injury in Group 3 was significantly lighter than that in Group 4. One week after reperfusion, serum NGAL, KIM-1, and Cys C levels in Group 3 were significantly lower than those in Group 4. Conclusion: Low-energy shock wave preconditioning can reduce renal ischemic reperfusion injury caused by renal artery occlusion in an isolated kidney rat model.
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Animais , Masculino , Ratos , Obstrução da Artéria Renal/complicações , Terapia por Ondas Curtas/métodos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/terapia , Precondicionamento Isquêmico/métodos , Rim/irrigação sanguínea , Ratos Sprague-Dawley , Modelos Animais de DoençasRESUMO
For the ß phase of Ti-5553-type metastable ß-Ti alloys, striations in transmission electron microscopy (TEM) bright- and dark-field images have been frequently observed but their origin has not been sufficiently investigated. In the present work, this phenomenon is studied in depth from the macroscopic scale by neutron diffraction to the atomic scale by high-resolution TEM. The results reveal that the ß phase contains homogeneously distributed modulated structures, intermediate between that of the ß phase (cubic) and that of the α phase or the ω phase (hexagonal), giving rise to the appearance of additional diffraction spots at 1/2, 1/3 and 2/3 ß diffraction positions. The intermediate structure between ß and α is formed by the atomic displacements on each second {110}ß plane in the [Formula: see text] direction, whereas that between ß and ω is formed by atomic displacements on each second and third {112}ß plane in the opposite [Formula: see text] direction. Because of these atomic displacements, the {110}ß and {112}ß planes become faulted, resulting in the streaking of ß diffraction spots and the formation of extinction fringes in TEM bright- and dark-field images, the commonly observed striations. The present work reveals the origin of the striations and the intrinsic correlation with the additional electron reflections of the ß phase.
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Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. The combination of psychostimulants and opioids produces more serious effects than either drug alone and is responsible for numerous deaths. In recent years, owing to its increased use, methamphetamine (METH), a psychostimulant, has become a popular choice for use in combination with opioids, especially heroin. However, little is known about the neurotoxicity of METH/heroin combination. The aims of this study were to evaluate whether METH/heroin combination was more neurotoxic than either drug alone and analyze the possible neurotoxic mechanisms using rat pheochromocytoma (PC12) cells. Our data showed that METH/heroin combination exhibited a significant decrease in cell viability than either drug alone, and the coefficient of drug interaction (CDI) indicated that the combination appeared to produce synergistic effects. Further studies showed that METH/heroin combination induced apoptosis and decreased the mitochondrial potential significantly, compared to either drug alone. This was demonstrated by a significant decrease in the expression of Bcl-2 and an increase in expression of Bax, accompanied by increase in the activities of caspase-3 and caspase-9. These results suggest that the combination of METH and heroin is more neurotoxic than either drug alone, and it induces apoptosis via the mitochondrial apoptotic pathway.
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Estimulantes do Sistema Nervoso Central/toxicidade , Heroína/toxicidade , Metanfetamina/toxicidade , Entorpecentes/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células PC12 , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RatosRESUMO
Prostate cancer is one of the most common male malignancies, although it rarely metastasizes to the ureter. The present case study reported a 63-year-old man who presented with asymptomatic right hydronephrosis, detected by ultrasound. Computed tomography urography demonstrated right hydronephrosis, secondary to thickening of the distal ureter. The patient's serum concentration of prostate specific antigen was 111.400 ng/ml, and a prostate needle biopsy revealed prostate adenocarcinoma, with a Gleason score of 4+5=9. Renal scintigraphy revealed poor excretion of the right kidney. A nephroureterectomy was subsequently performed, and a histological examination revealed a metastatic prostate adenocarcinoma of the ureter. Combined androgen blockage therapy with bicalutamide (50 mg, once daily) and goserelin (3.6 mg, once a month) was administered to the patient. At 3 months of follow-up, the patient's PSA levels had decreased to 0.322 ng/ml; at 6 months of follow-up, the PSA levels had further decreased to 0.136 ng/ml.
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To investigate all the predictors of operative duration, hospital stay and stone-free rate post-minimally invasive percutaneous nephrolithotomy (MPCNL) and to establish a logistic regression formula to predict the probability of stone-free post-MPCNL. From August 2009 to August 2012, 396 patients were enrolled in the present study. The patients' characteristics, history, laboratory examination and imaging information were used as independent variables, and operative duration, hospital stay, residuals (≥4 mm) as outcomes. Univariate and multiple regression analysis were performed to determine independent variables. According to the result of multiple logistic regression analysis, a logistic regression formula was established to predict the stone-free probability post-MPCNL. The predictors of operative duration were type of stones and stone burden. Factors affecting hospital stay included leucocytes, stone burden, type of stones and hemoglobin. Residuals were significantly related with stone burden and type of stones. With the above results, we developed a logistic regression formula, which can effectively predict the probability of stone-free with 91.7% of sensitivity, 70.4% of specificity and 85.9% of overall accuracy.
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Técnicas de Apoio para a Decisão , Cálculos Renais/cirurgia , Nefrostomia Percutânea , Adulto , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
In the present study, we compared the expression of miRNAs and angiogenesis-related genes in the renal tumors and adjacent normal renal tissues of patients with clear cell renal cell carcinoma (ccRCC). The first part of the present study was a preliminary analysis of 4 patients with stage T1a/b ccRCC that measured the levels of angiogenesis and expression of angiogenesis-related genes and miRNAs in the tumors and adjacent normal renal tissues. The second part of this study was an analysis of 30 patients with stage T1, T2 or T3 ccRCC that employed qPCR to characterize expression of angiogenesis-related miRNAs in the tumors and adjacent normal tissues. The first part of this study indicated that all 4 patients had increased levels of CD34 in tumors, indicating elevated angiogenesis. However, quantitative analysis of microvessel density and expression of miRNAs indicated highly variable results among these patients. The data of all patients in the present study indicated that more patients with stage T1 ccRCC had higher expression of miR-126 and miR-378 in their normal tissues, whereas more patients with stage T2/3 ccRCC had higher expression of these miRNAs in their tumor tissues. The tumors of patients with ccRCC had lower expression of miR-126 and miR-378 during the early stages of disease (T1), but higher expression of these miRNAs during the later stages of disease (T2/T3).
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Carcinoma de Células Renais/genética , Neoplasias Renais/genética , MicroRNAs/genética , Neovascularização Patológica/genética , Idoso , Antígenos CD34/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Rim/irrigação sanguínea , Rim/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismoRESUMO
Many studies have reported the role of glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism with prostate cancer (PCa) risk. However, these studies have yielded conflicting results. Hence, we performed this meta-analysis to investigate the association between GSTP1 Ile105Val polymorphism and PCa in different inheritance models. A total of 13 eligible studies were pooled into this meta-analysis. There was significant association between the GSTP1 Ile158Val variant genotypes and PCa for Ile/Ile vs Val/Val comparison [odds ratio (OR) =0.705; I (2) =63.7 %; 95 % confidence interval (95 % CI) = 0.508-0.977], Ile/Val vs Val/Val comparison (OR=0.736; I (2) =8.0 %; 95 % CI=0.613-0.883), and dominant model (OR=0.712; I (2) =45.5 %; 95 % CI=0.555-0.913). However, no associations were detected for other genetic models. In the stratified analysis by ethnicity, significant associations between GSTP1 Ile105Val polymorphism and PCa risk were also found among Caucasians (Ile/Ile vs Val/Val comparison OR=0.818, I (2) =0.0 %, 95 % CI=0.681-0.982; Ile/Val vs Val/Val comparison OR=0.779, I (2) =0.0 %, 95 % CI=0.651-0.933; and dominant model OR=0.794, I (2) =0.0 %, 95 % CI=0.670-0.941), while there were no associations found for other genetic models. However, no associations were found in Asians and African-Americans for all genetic models when stratified by ethnicity. In conclusion, our meta-analysis indicates that GSTP1 Ile105Val polymorphisms contributed to the PCa susceptibility. However, a study with the larger sample size is needed to further evaluate gene-environment interaction on GSTP1 Ile105Val polymorphisms and PCa risk.
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Predisposição Genética para Doença , Glutationa S-Transferase pi/genética , Polimorfismo Genético/genética , Neoplasias da Próstata/etiologia , Estudos de Casos e Controles , Humanos , Masculino , Metanálise como Assunto , Fatores de RiscoRESUMO
Rapamycin has been reported to inhibit hepatic fibrosis, lung fibrosis, renal fibrosis, and subglottic stenosis. Fibrosis is also involved in urethral stricture. Therefore, we investigated the effect of rapamycin on the inhibition of urethral stricture formation in a rabbit model. First, models of urethral stricture were successfully established by electrocoagulation of the bulbar urethra in adult New Zealand male rabbits. Forty-six model rabbits were randomly assigned to four groups: high-dose rapamycin (R(H), 1.0 mg/day), low-dose rapamycin (R(L), 0.1 mg/day), dimethyl sulfoxide (DMSO) alone (DMSO, solvent control), and normal saline (NS). Urethral stricture was assessed by a retrograde urethrogram and video-urethroscopy. Urethra pathology was evaluated by hematoxylin and eosin and Sirius red staining. After 28 days of treatment, lumen reduction in the R(H), R(L), DMSO, and NS groups was 36.0, 56.5, 69.1, and 82.9, respectively. Comparison of the rapamycin groups (R(H) and R(L)) and control groups (DMSO and NS) indicated significantly less restriction in the rapamycin groups. Histopathological analysis confirmed the presence of fibroblasts and an increase in collagen at the stricture site in the two control groups but not in the R(H) or R(L) groups. These results indicate that rapamycin inhibits experimentally induced urethral stricture formation in rabbits. This effect may be due to its inhibition of fibroblast proliferation and collagen expression.
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Modelos Animais de Doenças , Sirolimo/uso terapêutico , Estreitamento Uretral/patologia , Estreitamento Uretral/prevenção & controle , Animais , Relação Dose-Resposta a Droga , Masculino , Projetos Piloto , Coelhos , Distribuição AleatóriaRESUMO
OBJECTIVE: To investigate the effects of prepubertal exposure to estradiol benzoate (EB) on the testicular development and function of SD rats. METHODS: Fifty four 21-day-old male SD rats were randomly and equally divided into 2 experimental groups (AEa and AEb, n = 18 each) and one control group (AC, n = 18). The rats in the experimental groups were injected (s. c.) with EB dissolved in corn oil at a dose of 0.1 (AEa) and 100.0 microg/(kg x d) (AEb) respectively during prepuberty for 14 d [from postnatal day (PND) 22 to PND 35]. The rats in the control group received vehicle injections only. The testicular development of the rats was observed. The testes were harvested at the stages of late puberty (PND 50), sexual maturity (PND 64) and adulthood (PND 130) (n = 6 at each stage). The serum testosterone, the weights and histology of the testes, and the quality of sperms in the epididymal cauda were examined. RESULTS: The testes of rats in group AEb descended at day 43.17 +/- 1.72, later than the rats in the AC group (27.00 +/- 0.89, P < 0.01). At the stage of late puberty, the AEb group had lower serum testosterone than the AC group (P < 0.05) and had less unilateral testes weights than the AC group (P < 0.01). Compared with the AC group, the histological alteration of the testes of rats in the AEb group included seminiferous tubules maldevelopment, decreased cell numbers of seminiferous epithelia, spermatogenesis blocking and Leydig cells aplasia. At the stage of sexual maturity, the AEb group had less unilateral testes weight than the AC group (P < 0.01) and maintained similar histological alterations of testes as at the stage of late puberty. At the stage of adulthood, no differences were observed among the three groups in the unilateral testes weights and the histological features of the testes (P > 0.05). However, the AEb group had significant lower density and motility of sperms and percentage of grade a+b sperms in the epididymal cauda than the AC group (P < 0.05). CONCLUSION: Prepubertal exposure to low dose of EB does not affect the testicular development and function of SD rats, while high dose [100 microg/(kg x d) x 14 d] exposure has significant short (PND 50 and 64) and long-term (PND 130) toxic effects. The toxic effects are associated with the damage of Leydig and Sertoli cells.