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BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA) requiring urgent treatment. Standardization of its diagnosis and optimal management is challenging. This study aimed to evaluate the role of centralized, rapid testing of ADAMTS13 in patients experiencing acute TMAs requiring plasma-exchange (PEX) and to estimate the incidence of TTP in a large Italian Region. METHODS: We perfomed a cohort study in the frame of the project "Set-up of a Lombardy network for the study and treatment of patients undergoing apheresis", including 11 transfusion centers in the Region. Consecutive patients referred from 2014 to 2016 with acute TMAs requiring PEX were enrolled. Centralized ADAMTS13 activity testing was performed at the Milan Hemophilia and Thrombosis Center within 24 h. RESULTS: Forty-three TMA patients (44 events) were enrolled, of whom 35 (81%) had severe ADAMTS13 deficiency. Patients with severe ADAMTS13 deficiency were younger, mainly women, with a higher prevalence of autoimmune disorders and a lower prevalence of cancer. Clinical and laboratory characteristics of patients with and without severe ADAMTS13 deficiency largely overlapped, with a lower platelet count being the only baseline marker that significantly differed between the two patient groups (ADAMTS13 activity < 10% vs ≥ 10%: median difference of -27 × 109/l, 95% CI - 37 to - 3). PEX treatment was initiated in all patients, but soon discontinued in cases without severe ADAMTS13 deficiency. In this group, the mortality rate was higher and no episode exacerbations or relapses within 6 months occured. The estimated average annual incidence of acute acquired TTP events was 1.17 [0.78-1.55] per million people. CONCLUSIONS: Severe ADAMTS13 deficiency distinguished two groups of patients with largely overlapping clinical features but different treatment and disease course. This study provides a feasible model implemented in a large Italian region for the practical clinical approach to TMAs and underlines the importance of urgent ADAMTS13 activity testing for an accurate differential diagnosis and therapeutic approach.
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Proteína ADAMTS13 , Púrpura Trombocitopênica Trombótica , Trombose , Microangiopatias Trombóticas , Proteína ADAMTS13/deficiência , Estudos de Coortes , Feminino , Humanos , Troca Plasmática , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/epidemiologia , Púrpura Trombocitopênica Trombótica/terapia , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/terapiaRESUMO
Recent research has been focusing on the generation of living personalized osteochondral constructs for joint repair. Native articular cartilage has a zonal structure, which is not reflected in current constructs and which may be a cause of the frequent failure of these repair attempts. Therefore, we investigated the performance of a composite implant that further reflects the zonal distribution of cellular component both in vitro and in vivo in a long-term equine model. Constructs constituted of a 3D-printed poly(ϵ-caprolactone) (PCL) bone anchor from which reinforcing fibers protruded into the chondral part of the construct over which two layers of a thiol-ene cross-linkable hyaluronic acid/poly(glycidol) hybrid hydrogel (HA-SH/P(AGE-co-G)) were fabricated. The top layer contained Articular Cartilage Progenitor Cells (ACPCs) derived from the superficial layer of native cartilage tissue, the bottom layer contained mesenchymal stromal cells (MSCs). The chondral part of control constructs were homogeneously filled with MSCs. After six months in vivo, microtomography revealed significant bone growth into the anchor. Histologically, there was only limited production of cartilage-like tissue (despite persistency of hydrogel) both in zonal and non-zonal constructs. There were no differences in histological scoring; however, the repair tissue was significantly stiffer in defects repaired with zonal constructs. The sub-optimal quality of the repair tissue may be related to several factors, including early loss of implanted cells, or inappropriate degradation rate of the hydrogel. Nonetheless, this approach may be promising and research into further tailoring of biomaterials and of construct characteristics seems warranted.
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Cartilagem Articular/patologia , Hidrogéis/química , Impressão Tridimensional , Regeneração , Âncoras de Sutura , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Condrócitos/patologia , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Cavalos , Ácido Hialurônico/farmacologia , Células-Tronco Mesenquimais/citologia , Tamanho do Órgão , Compostos de Sulfidrila/farmacologiaAssuntos
Apoptose/genética , Caspase 10/genética , Caspase 8/genética , Mutação , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/etiologia , Proteína ADAMTS13/genética , Proteína ADAMTS13/metabolismo , Adolescente , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Biomarcadores , Caspase 10/metabolismo , Caspase 8/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Proteólise , Púrpura Trombocitopênica Trombótica/tratamento farmacológicoRESUMO
Since Galileo's days the effect of size on the anatomical characteristics of the structural elements of the body has been a subject of interest. However, the effects of scaling at tissue level have received little interest and virtually no data exist on the subject with respect to the osteochondral unit in the joint, despite this being one of the most lesion-prone and clinically relevant parts of the musculoskeletal system. Imaging techniques, including Fourier transform infrared imaging, polarized light microscopy and micro computed tomography, were combined to study the response to increasing body mass of the osteochondral unit. We analyzed the effect of scaling on structural characteristics of articular cartilage, subchondral plate and the supporting trabecular bone, across a wide range of mammals at microscopic level. We demonstrated that, while total cartilage thickness scales to body mass in a negative allometric fashion, thickness of different cartilage layers did not. Cartilage tissue layers were found to adapt to increasing loads principally in the deep zone with the superficial layers becoming relatively thinner. Subchondral plate thickness was found to have no correlation to body mass, nor did bone volume fraction. The underlying trabecular bone was found to have thicker trabeculae (r=0.75, p<0.001), as expected since this structure carries most loads and plays a role in force mitigation. The results of this study suggest that the osteochondral tissue structure has remained remarkably preserved across mammalian species during evolution, and that in particular, the trabecular bone carries the adaptation to the increasing body mass.
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Peso Corporal , Osso e Ossos/anatomia & histologia , Mamíferos/anatomia & histologia , Animais , Osso Esponjoso/anatomia & histologia , Cartilagem Articular/anatomia & histologia , Colágeno/metabolismo , Humanos , Proteoglicanas/metabolismo , Especificidade da Espécie , Espectroscopia de Infravermelho com Transformada de Fourier , Microtomografia por Raio-XRESUMO
OBJECTIVE: To investigate the potential of quantitative susceptibility mapping (QSM) and T2* relaxation time mapping to determine mechanical and structural properties of articular cartilage via univariate and multivariate analysis. METHODS: Samples were obtained from a cartilage repair study, in which surgically induced full-thickness chondral defects in the stifle joints of seven Shetland ponies caused post-traumatic osteoarthritis (14 samples). Control samples were collected from non-operated joints of three animals (6 samples). Magnetic resonance imaging (MRI) was performed at 9.4 T, using a 3-D multi-echo gradient echo sequence. Biomechanical testing, digital densitometry (DD) and polarized light microscopy (PLM) were utilized as reference methods. To compare MRI parameters with reference parameters (equilibrium and dynamic moduli, proteoglycan content, collagen fiber angle and -anisotropy), depth-wise profiles of MRI parameters were acquired at the biomechanical testing locations. Partial least squares regression (PLSR) and Spearman's rank correlation were utilized in data analysis. RESULTS: PLSR indicated a moderate-to-strong correlation (ρ = 0.49-0.66) and a moderate correlation (ρ = 0.41-0.55) between the reference values and T2* relaxation time and QSM profiles, respectively (excluding superficial-only results). PLSR correlations were noticeably higher than direct correlations between bulk MRI and reference parameters. 3-D parametric surface maps revealed spatial variations in the MRI parameters between experimental and control groups. CONCLUSION: Quantitative parameters from 3-D multi-echo gradient echo MRI can be utilized to predict the properties of articular cartilage. With PLSR, especially the T2* relaxation time profile appeared to correlate with the properties of cartilage. Furthermore, the results suggest that degeneration affects the QSM-contrast in the cartilage. However, this change in contrast is not easy to quantify.
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Cartilagem Articular/patologia , Cartilagem Articular/fisiopatologia , Osteoartrite/patologia , Osteoartrite/fisiopatologia , Animais , Fenômenos Biomecânicos , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/lesões , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Cavalos , Imageamento por Ressonância Magnética , Masculino , Osteoartrite/diagnóstico por imagem , Osteoartrite/etiologiaRESUMO
Water resource recovery facilities (WRRFs) contribute to climate change and air pollution, as they are anthropogenic potential sources of direct and indirect emission of greenhouse gases (GHGs). Studies concerning the monitoring and accounting for GHG emissions from WRRFs are of increasing interest. In this study, the floating hood technique for gas collection was coupled with the off-gas method to monitor and apportion nitrous oxide (N2O) and carbon dioxide (CO2) emissions from both aerated and non-aerated tanks in a municipal water resource recovery facility, in order to investigate its carbon footprint (CFP). To our knowledge, this is the first time that the chamber technique was applied to evaluate gas fluxes from the settler, where an emission factor (EF) of 4.71â¯∗â¯10-5â¯kgCO2,eqâ¯kgbCOD-1 was found. Interesting results were found in the disinfection unit, which was the major contributor to direct N2O emissions (with a specific emission factor of 0.008â¯kgCO2,eqâ¯kgbCOD-1), due to the chemical interaction between hydroxylamine and the disinfectant agent (hypochlorite). The specific emission factor of the biological aerated tank was 0.00112â¯kgCO2,eqâ¯kgbCOD-1. The average direct CO2 emission was equal to 0.068â¯kgCO2â¯kgbCOD-1 from the activated sludge tank and to 0.00017â¯kgCO2â¯kgbCOD-1 from the secondary clarifier. Therefore, taking into account the contribution of both direct N2O and CO2 emissions, values of 0.069â¯kgCO2,eqâ¯kgbCOD-1, 0.008â¯kgCO2,eqâ¯kgbCOD-1 and 0.00022â¯kgCO2,eqâ¯kgbCOD-1, were found for the net CFP of the aerated compartment, the disinfection unit and the clarifier, respectively. The plant energy Footprint (eFP) was also evaluated, confirming that the aeration system is the major contributor to energy consumption, as well as to indirect CO2 emission, with a specific eFP of 1.49â¯kWhâ¯kgbCOD-1.
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Essentials ISTH Bleeding Assessment Tool (ISTH-BAT) is used to assist the diagnosis of bleeding disorders. We examined whether the ISTH-BAT is capable of predicting the risk of future bleeding. 136 subjects were administered the ISTH-BAT and followed for up to four years. The ISTH-BAT score failed to predict the risk of future bleeding. SUMMARY: Background The ISTH Bleeding Assessment Tool (ISTH-BAT) is a diagnostic tool used in subjects with suspected inherited bleeding disorders. Aim To evaluate whether the ISTH-BAT, applied at first work-up in a tertiary-care center, predicts the risk of subsequent bleeding events. Methods This was an observational cohort study including all consecutive subjects, of either sex and any age, referred between 2011 and 2015 because of a suspected bleeding disorder. The analysis was restricted to those with an ISTH-BAT score of ≥ 3. Incidence rates (IRs) of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) events were calculated as the number of events over accrued person-years. The main analysis was performed with Cox regression analysis, assessing an ISTH-BAT score of ≤ 5 versus a score of > 5, as well as the score as a continuous variable, and various covariates (sex, age, and presence/absence of a final diagnosis). Results One hundred and thirty-six subjects had a median ISTH-BAT score of 4 (range 3-18). Eleven subjects (8.1%) had a bleeding event during follow-up (one MB event; 10 CRNMB events). The overall IR of bleeding events per 100 person-years was 3.7 (95% confidence interval [CI] 1.8-6.6). No difference was observed between subjects with an ISTH-BAT score of ≤ 5 and those with a score of > 5 (hazard ratio [HR] 1.2, 95% CI 0.3-4.6). The results were similar when the ISTH-BAT score was considered as a continuous variable (HR 1.1, 95% CI 0.9-1.4). The IR of bleeding was increased in individuals with a diagnosis of a hemostatic defect (IR of 7.5 per 100 person-years; HR 3.0, 95% CI 0.8-11.8). Conclusions The ISTH-BAT does not identify patients at increased risk of future bleeding events.
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Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Coagulação Sanguínea , Técnicas de Apoio para a Decisão , Hemorragia/diagnóstico , Adolescente , Adulto , Transtornos Herdados da Coagulação Sanguínea/sangue , Transtornos Herdados da Coagulação Sanguínea/genética , Feminino , Hemorragia/sangue , Hemorragia/genética , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case-control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02-3.27, P = 1.64 × 10-14 ). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10-5 to 7.60 × 10-5 ). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10-19 ). Imputation of classic HLA genes followed by stepwise conditional analysis revealed that the combination of rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in acquired TTP. Our results refined the association of the HLA class II locus with acquired TTP, confirming its importance in the etiology of this autoimmune disease.
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Predisposição Genética para Doença , Cadeias beta de HLA-DQ/genética , Púrpura Trombocitopênica Trombótica/genética , Adulto , Alelos , Autoanticorpos/imunologia , Autoimunidade , Estudos de Casos e Controles , Mapeamento Cromossômico , Europa (Continente) , Feminino , Genótipo , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , Fatores de RiscoRESUMO
We report the case of a patient presenting meningeal carcinomatosis and cutanenous metastasis as first manifestation of gastric adenocarcinoma. A 57-year-old patient was hospitalized because of headache and diplopia. Clinical examination revealed VI cranial nerve paralysis and anterior neck infiltration. Cutaneous biopsy and umbar puncture showed signet ring-cells. Extensive work-up disclosed gastric adenocarcinoma. Cutaneous metastasis and carcinomatous metastasis are both present exceptionally as first manifestation of gastric adenocarcinoma. We discuss frequency, etiology and treatment of these manifestations.
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Adenocarcinoma/patologia , Adenocarcinoma/secundário , Neoplasias Cutâneas/secundário , Humanos , Masculino , Neoplasias Meníngeas/secundário , Pessoa de Meia-Idade , Pescoço , Neoplasias Gástricas/patologiaRESUMO
PURPOSE: We evaluated the rate of significant colonic and extra-colonic abnormalities at computed tomography colonography (CTC), according to symptoms and age. MATERIALS AND METHODS: We retrospectively evaluated 7361 consecutive average-risk subjects (3073 males, average age: 60.3 ± 13.9; range 18-96 years) for colorectal cancer (CRC) who underwent CTC. They were divided into three groups according to clinical symptoms: 1343 asymptomatic individuals (group A), 899 patients with at least one "alarm" symptom for CRC, including rectal bleeding and unexplained weight loss (group C), and 5119 subjects with other gastrointestinal symptoms (group B). Diagnostic and test-positive rates of CTC were established using optical colonoscopy (OC) and/or surgery as reference standard. In addition, clinically significant extra-colonic findings were noted. RESULTS: 903 out of 7361 (12%, 95% confidence interval (CI) 0.11-0.13) subjects had at least one clinically significant colonic finding at CTC. CTC true positive fraction and false positive fraction were respectively 637/642 (99.2%, 95%CI 0.98-0.99) and 55/692 (7.95%, 95%CI 0.05-0.09). The pooled test-positive rate in group C (138/689, 20.0%, 95%CI 0.17-0.23) was significantly higher than in both groups A (79/1343, 5.9%, 95%CI 0.04-0.07) and B (420/5329, 7.5%, 95%CI 0.07-0.08) (p < 0.001). Aging and male gender were associated to a higher test positive rate. The rate of clinically significant extra-colonic findings was significantly higher in group C (44/689, 6.4%, 95%CI 0.04-0.08) versus groups A (26/1343, 1.9%, 95%CI 0.01-0.02) and B (64/5329, 1.2%, 95%CI 0.01-0.02) (p < 0.001). CONCLUSION: Both test-positive and significant extra-colonic finding rates at CTC are significantly increased in the presence of "alarm" gastrointestinal symptoms especially in older patients.
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Contrast-enhanced cardiac magnetic resonance imaging allows the evaluation of both myocardial perfusion and myocardial tissue characteristics. This paper reviews different microvascular and non-vascular conditions that can cause abnormal findings on contrast-enhanced myocardial magnetic resonance imaging. Knowledge of their characteristics can avoid misinterpretation and avoid inappropriate referral for further invasive imaging in patients suspected of myocardial vascular disease.
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Meios de Contraste , Cardiopatias/diagnóstico , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Miocárdio/patologia , Doenças Vasculares/diagnóstico , Cardiopatias/patologia , Humanos , Angiografia por Ressonância Magnética/métodos , Doenças Vasculares/patologiaRESUMO
Collagen-binding activity (CBA) and FRETS-VWF73 assays are widely adopted methods for the measurement of the plasmatic activity of ADAMTS13, the von Willebrand factor (VWF) cleaving-protease. Accurately assessing the severe deficiency of ADAMTS13 is important in the management of thrombotic thrombocytopenic purpura (TTP). However, non-concordant results between the two assays have been reported in a small but relevant percentage of TTP cases. We investigated whether CBA or FRETS-VWF73 assay reflects ADAMTS13 proteolytic activity in acquired TTP patients with non-concordant measurements. Twenty plasma samples with non-concordant ADAMTS13 activity results, <10% using FRETS-VWF73 and ≥20% using CBA, and 11 samples with concordant results, <10% using either FRETS-VWF73 and CBA assays, were analysed. FRETS-VWF73 was performed in the presence of 1.5 M urea. ADAMTS13 activities were also measured under flow conditions and the VWF multimer pattern was defined in order to verify the presence of ultra-large VWF due to ADAMTS13 deficiency. In FRETS-VWF73 assay with 1.5 M urea, ADAMTS13 activity significantly increased in roughly 50% of the samples with non-concordant results, whereas it remained undetectable in all samples with concordant measurements. Under flow conditions, all tested samples showed reduced ADAMTS13 activity. Finally, samples with non-concordant results showed a ratio of high molecular weight VWF multimers higher than normal. Our results support the use of FRETS-VWF73 over CBA assay for the assessment of ADAMTS13 severe deficiency and indicate urea as one cause of the observed differences.
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Proteínas ADAM/deficiência , Colágeno/metabolismo , Transferência Ressonante de Energia de Fluorescência , Púrpura Trombocitopênica Trombótica/diagnóstico , Fator de von Willebrand/metabolismo , Proteína ADAMTS13 , Humanos , Valor Preditivo dos Testes , Ligação Proteica , Desnaturação Proteica , Proteólise , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/enzimologia , Sistema de Registros , Reprodutibilidade dos Testes , Ureia/químicaRESUMO
The present study addresses the theme of recycling potential of old open dumpsites by using landfill mining. Attention is focused on the possible reuse of the residual finer fraction (<4 mm), which constitutes more than 60% of the total mined material, sampled in the old open dumpsite of Lavello (Southern Italy). We propose a protocol of analysis of the landfill material that links chemical analyses and environmental bioassays. This protocol is used to evaluate the compatibility of the residual matrix for the disposal in temporary storages and the formation of "bio-soils" to be used in geo-environmental applications, such as the construction of barrier layers of landfills, or in environmental remediation activities. Attention is mainly focused on the presence of heavy metals and on the possible interaction with test organisms. Chemical analyses of the residual matrix and leaching tests showed that the concentration of heavy metals is always below the legislation limits. Biological acute tests (with Lepidum sativum, Vicia faba and Lactuca sativa) do not emphasize adverse effects to the growth of the plant species, except the bioassay with V. faba, which showed a dose-response effect. The new developed chronic bioassay test with Spartium junceum showed a good adaptation to stress conditions induced by the presence of the mined landfill material. In conclusion, the conducted experimental activities demonstrated the suitability of the material to be used for different purposes.
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Monitoramento Ambiental , Metais Pesados/toxicidade , Poluentes do Solo/toxicidade , Spartium/efeitos dos fármacos , Produtos Agrícolas/efeitos dos fármacos , Itália , Reciclagem , Eliminação de Resíduos , Testes de Toxicidade Crônica , Instalações de Eliminação de ResíduosRESUMO
BACKGROUND: The formation of ADAMTS13-specific circulating immune complexes (CICs) may be a pathophysiologic mechanism in autoimmune thrombotic thrombocytopenic purpura (TTP), but has not been systematically investigated. OBJECTIVES: (a) To develop an assay for ADAMTS13-specific CICs; (b) to evaluate their prevalence in autoimmune TTP; and (c) to assess their association with ADAMTS13-related measurements and clinical features in autoimmune TTP patients. PATIENTS/METHODS: We developed and validated an ELISA method for ADAMTS13-specific CICs. ADAMTS13-specific CICs were searched for in 55 patients with autoimmune TTP from the Milan TTP Registry (URL:http://www.ttpdatabase.org/) and 28 controls. The associations between ADAMTS13-specific CIC levels and ADAMTS13 activity, antigen, anti-ADAMTS13 IgGs and acute TTP clinical features were assessed by multivariate linear regression. RESULTS: Intra- and inter-assay coefficients of variation of the new test were 5.3 and 9.6%. In 36 patients with severe ADAMTS13 deficiency and anti-ADAMTS13 autoantibodies, the prevalence of ADAMTS13-specific CICs was 47% (n = 17; 95% confidence interval [CI], 32-63%). ADAMTS13-specific CICs were detected also in seven of 19 (37%; 95% CI, 19-59%) patients with reduced ADAMTS13 activity, but apparently negative anti-ADAMTS13 autoantibodies. ADAMTS13-specific CICs were not associated with ADAMTS13 activity, antigen or anti-ADAMTS13 IgGs. In patients with acute TTP, increasing levels of ADAMTS13-specific CICs were associated with a higher number of plasma-exchange procedures required to attain remission (per 0.1 increase in normalized OD values, beta, 2.9; 95% CI, -0.7 to 6.5). CONCLUSIONS: Approximately one to two-thirds of patients with autoimmune TTP display ADAMTS13-specific CICs. A thorough investigation of the prognostic relevance of ADAMTS13-specific CIC levels in autoimmune TTP is warranted.
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Proteínas ADAM/sangue , Complexo Antígeno-Anticorpo/sangue , Doenças Autoimunes/sangue , Púrpura Trombocitopênica Trombótica/sangue , Proteínas ADAM/imunologia , Proteína ADAMTS13 , Adulto , Doenças Autoimunes/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Prognóstico , Sistema de Registros , Reprodutibilidade dos Testes , Fator de von Willebrand/metabolismoRESUMO
AIMS: This study was designed to investigate whether culture conditions (media, seawater concentration and pH) could lead Streptomyces sundarbansensis strain (isolated from marine brown algae Fucus sp. collected from Algerian coastline) to produce bioactive secondary metabolites. The most favourable condition for the production of anti-MRSA compound 1 [2-hydroxy-5-((6-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-2-propylchroman-4-one] was determined. METHODS AND RESULTS: The profile of metabolites present in the crude extracts was carried out by HPLC analysis equipped with a diode array detector evaporative light scattering detection (DAD-ELSD) or online coupled to electrospray ionization-mass spectrometry (ESI-MS). Compound 1 was the most abundant secondary metabolite by culturing the strains on starch casein agar (SCA) medium in freshwater or 50% seawater at pH 7 or 9 using agar-state fermentation method. CONCLUSIONS: The study has shown the efficiency of HPLC/ESI-MS technique in the analysis of polyketides produced by the strain under investigation. It was possible to establish the best culture conditions for obtaining the most bioactive compound 1, previously isolated by the same strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Marine algae-actinobacteria associations are a particularly promising renewable system for the production of new antibacterial metabolites. Based on the promising bioactivity of the chemically characterized compound 1, the analytical methodology here applied has resulted as an effective approach for establishing its optimized production.
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Antibacterianos , Streptomyces , Antibacterianos/química , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Meios de Cultura/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Streptomyces/metabolismoRESUMO
In recent years, the replacement of natural raw materials with new alternative materials, which acquire an economic, energetic and environmental value, has gained increasing importance. The considerable consumption of water has favoured the increase in the number of drinking water treatment plants and, consequently, the production of drinking water sludge. This paper proposes a protocol of analyses capable of evaluating chemical characteristics of drinking water sludge from surface water treatment plants. Thereby we are able to assess their possible beneficial use for geo-environmental applications, such as the construction of barrier layers for landfill and for the formation of "bio-soils", when mixed with the stabilized organic fraction of municipal solid waste. This paper reports the results of a study aimed at evaluating the quality and environmental aspects of reconstructed soils ("bio-soil"), which are used in much greater quantities than the usual standard, for "massive" applications in environmental actions such as the final cover of landfills. The granulometric, chemical and physical analyses of the sludge and the leaching test on the stabilized organic fraction showed the suitability of the proposed materials for reuse. The study proved that the reuse of drinking water sludge for the construction of barrier layers and the formation of "bio-soils" reduces the consumption of natural materials, the demand for landfill volumes, and offers numerous technological advantages.
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Água Potável , Esgotos/análise , Purificação da Água , Bioensaio , Materiais de Construção , Germinação , Itália , Lactuca/fisiologia , Metais Pesados/análise , Resíduos Sólidos , Spartium/fisiologia , Instalações de Eliminação de ResíduosAssuntos
Bioprótese , Colesteatoma da Orelha Média/cirurgia , Prótese Ossicular , Otite Média Supurativa/cirurgia , Otite Média/cirurgia , Desenho de Prótese , Perfuração da Membrana Timpânica/cirurgia , Adulto , Idoso , Audiometria de Tons Puros , Bancos de Ossos , Condução Óssea , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Ajuste de PróteseRESUMO
Infrared multiple-photon dissociation spectroscopy has been used to record vibrational spectra of charged copper-resveratrol complexes in the 3500-3700 cm(-1) and 1100-1900 cm(-1) regions. Minimum energy structures have been determined by density functional theory calculations using plane waves and pseudopotentials. In particular, the copper(I)-resveratrol complex presents a tetra-coordinated metal bound with two carbon atoms of the alkenyl moiety and two closest carbons of the adjoining resorcinol ring. For these geometries vibrational spectra have been calculated by using linear response theory. The good agreement between experimental and calculated IR spectra for the selected species confirms the overall reliability of the proposed geometries.
Assuntos
Cobre/química , Teoria Quântica , Estilbenos/química , Modelos Moleculares , Conformação Molecular , Resveratrol , Espectrofotometria InfravermelhoRESUMO
BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening disease. Of surviving patients, 45% develops an exacerbation or a late recurrence. Severe ADAMTS-13 deficiency, both during the acute episode and remission, is a well-established predictor of recurrence. The predictive value of anti-ADAMTS-13 antibodies, their inhibitory activity and Ig class subtype for disease recurrence is still to be established. OBJECTIVES: To analyze ADAMTS-13-related biomarkers (ADAMTS-13 and anti-ADAMTS-13 immunoglobulins, classes and subclasses) and their potential relationship with prognosis. PATIENTS/METHODS: In 115 patients with TTP, we assessed the association between levels of these biomarkers and the severity of acute episodes; we analysed also the hazard ratio (HR) and 95% confidence interval (CI) of recurrence in association with biomarkers levels retrieved at the previous acute episode or during remission, using Cox regression models. RESULTS: During the acute phase, higher IgA, IgG1 and IgG3 titers showed the strongest association with acute episode severity. In the survival analyzes, the only biomarker significantly associated with a high hazard of recurrence after an acute episode was the presence of IgG. Conversly, low ADAMTS-13 activity or antigen levels (<10%), the presence of ADAMTS-13 inhibitor or IgG during remission were all significantly associated with a higher hazard of recurrence. CONCLUSIONS: Both the Ig class and subclass are of predictive value for acute episode severity in patients with TTP. Although markers that could predict the risk of recurrence in the acute phase are limited, a thorough assessment of ADAMTS-13-related parameters during remission is warranted.