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1.
Polymers (Basel) ; 15(20)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37896402

RESUMO

In the field of encapsulation, microcapsules containing perfume have emerged as effective vehicles for delivering active ingredients across various applications. The present study employed a multivariate analysis framework to examine polyacrylate microcapsules for household products synthesized using different acrylate monomers. The advanced multivariate approach allowed us to quantify critical properties such as the Molecular Weight between Cross-links (MWc), mechanical attributes, Encapsulation Efficiency (EE), and On-Fabric delivery. It is worth noting that the mechanical properties were gauged using a novel nanoindentation technique, which measures the Rupture Force per unit diameter (RFD). Both Encapsulation Efficiency and On-Fabric delivery were assessed using GC-MS. Our findings identified the optimal microcapsule system as one synthesized with 100% aromatic hexafunctional urethane acrylate, showcasing a 94.3% Encapsulation Efficiency and an optimal RFD of 85 N/mm. This system achieved an exemplary On-Fabric delivery rate of 307.5 nmol/L. In summary, this research provides crucial insights for customizing microcapsule design to achieve peak delivery efficiency. Furthermore, by designing acrylic monomers appropriately, there is potential to reduce the amount of active ingredients used, owing to enhanced delivery efficiency and the optimization of other microcapsule properties. Such advancements pave the way for more environmentally friendly and sustainable production processes in the fast-moving consumer goods industry.

2.
RSC Adv ; 13(4): 2718-2726, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36741155

RESUMO

Measurement of the surface free energy (SFE) of a material allows the prediction of its adhesion properties. Materials can have microscale or sub-microscale surface inhomogeneities, engineered or random, which affect the surface macroscopic behaviour. However, quantitative characterization of the SFE at such length scales remains challenging in view of the variety of instruments and techniques available, the poor knowledge of critical variables and parameters during measurements and the need for appropriate contact models to derive the SFE from the measurements. Failure to characterize adhesion correctly may result in defective components or lengthy process optimization costing billions to industry. Conversely, for planar and homogeneous surfaces, contact angle (CA) measurements are standardized and allow for calculating the SFE using for example the Owen-Wendt model, relying only on the properties of the probing liquids. As such, we assessed and report here a method to correlate quantitative measurements of force-distance curves made with an atomic force microscope (AFM) and with silica and polystyrene (PS) colloidal probe pairs, with quantitative CA measurements and CA-derived SFE values. We measured five surfaces (mica, highly oriented pyrolytic graphite, thermally grown silica on silicon, silicon, and silicon with a super-hydrophobic coating), ranging from hydrophilic to super-hydrophobic, and found an excellent classification of the AFM measurements when these are represented by a set of principal components (PCs), and when both silica and PS colloidal probes are considered together. A regression of the PCs onto the CA measurements allows recovery of the SFE at the length scale of the colloidal probes, which is here ca. 1 micron. We found that once the PC-regression model is built, test sets of only ten AFM force-distance curves are sufficient to predict the local SFE with the calibrated silica and PS colloidal probes.

3.
Materials (Basel) ; 14(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500953

RESUMO

The increasing demand on the performance of existing structures, together with their degradation, is among the main drivers towards the development of innovative strengthening solutions. While such solutions are generally aimed at increasing the load-bearing capacity of structural elements, serviceability limit states also play an important role in ensuring the performance and durability of the structure. An experimental campaign was performed to assess the cracking behaviour of reinforced concrete beams strengthened with different typologies of Textile-Reinforced Concrete. The specimens were monitored using Digital Image Correlation (DIC) technology in order to obtain a quantitative evaluation of the evolution of the crack pattern throughout the whole test. Results show the beneficial effects of this retrofitting strategy both at ultimate limit states and serviceability limit states, provide detailed insights on the progression of damage in the specimens and highlight how different parameters impact the cracking behaviour of the tested elements.

4.
Materials (Basel) ; 15(1)2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35009432

RESUMO

Surface free energy (SFE) of titanium surfaces plays a significant role in tissue engineering, as it affects the effectiveness and long-term stability of both active coatings and functionalization and the establishment of strong bonds to the newly growing bone. A new contact-mechanics methodology based on high-resolution non-destructive elastic contacting nanoindentation is applied here to study SFE of micro- and nano-structured titanium surfaces, right after their preparation and as a function of exposure to air. The effectiveness of different surface treatments in enhancing SFE is assessed. A time-dependent decay of SFE within a few hours is observed, with kinetics related to the sample preparation. The fast, non-destructive method adopted allowed for SFE measurements in very hydrophilic conditions, establishing a reliable comparison between surfaces with different properties.

5.
Methods Mol Biol ; 2275: 27-47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34118030

RESUMO

In this chapter we describe: (1) the procedure for the synthesis of four single chain bolaamphiphiles, displaying chains of 12, 16, 20 and 30 methylene units and triphenylphosphonium moieties as headgroups (TPP1-TPP4); (2) the methods used to characterize TPP1-TPP4 spontaneous aggregation in aqueous solution. We illustrate the determination of Krafft point and cac by conductivity measurements and the procedures used to investigate dimensions, morphology, and stability by dynamic and dielectrophoretic laser light scattering, dialysis, transmission electron microscopy, and Raman spectroscopy measurements.


Assuntos
Furanos/química , Mitocôndrias/efeitos dos fármacos , Compostos Organofosforados/síntese química , Piridonas/química , Difusão Dinâmica da Luz , Microscopia Eletrônica de Transmissão , Estrutura Molecular , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Análise Espectral Raman , Água/química
6.
Ann Surg ; 251(2): 287-91, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20010087

RESUMO

OBJECTIVE: To identify predictive risk factors for conversion to open splenectomy and postoperative complications in patients undergoing elective laparoscopic splenectomy. BACKGROUND: The laparoscopic approach represents the "gold standard" for splenectomy, but its use in the treatment of splenomegaly and malignant disease is controversial. Factors that influence immediate outcome are clinical, anatomic, and pathologic. METHODS: Univariate and multivariate analyses of data from the Italian Registry of Laparoscopic Surgery of the Spleen, a multicenter database supported by 25 referral centers. Analysis of data (1993-2007) was performed on a series of patients (n = 676) undergoing elective laparoscopic splenectomy. Demographic data, the operative indications, the surgical technique applied, and any intra- and/or postoperative complications with respect to the patients were assessed. Records were analyzed retrospectively using the Student t test, the chi test, and logistic regression. RESULTS: Conversion to open splenectomy was necessary in 39 cases (5.8%). Perioperative deaths occurred in 3 cases (0.4%). There were no complications in 560 patients (82.8%), with a mean hospital stay of 5 days (range, 2-54). Overall, morbidity occurred in 116 patients (17.2%). Multivariate analysis found that the body mass index (P = 0.01) and the presence of hematologic malignancy (P < 0.001) were independent predictors for intraoperative complications and surgical conversion. Spleen longitudinal diameter (P = 0.001) and surgical conversion (P = 0.001) were independent predictors for the occurrence of postoperative complications. CONCLUSIONS: This large multicenter study provides evidence for the significance of predictive risk factors for intra- and postoperative complications in laparoscopic splenic surgery. Besides splenic dimensions, other factors like the patient's habitus and the specific underlying hematologic pathology should be recognized by the surgeon to reduce complications and initiate adequate treatment.


Assuntos
Laparoscopia , Esplenectomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Esplenectomia/efeitos adversos , Resultado do Tratamento
7.
Clin Rheumatol ; 39(4): 1331-1339, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31858339

RESUMO

OBJECTIVE: Autoimmune diseases are associated with psychological distress, resulting in greatly impaired quality of life. Tandem-Psychotherapy comprises trauma-focused psychotherapy with hypnosis and eye movement desensitization and reprocessing (EMDR), followed by supportive-expressive group therapy. The objective was to evaluate whether Tandem-Psychotherapy could reduce psychological distress and improve quality of life. METHODS: In a case-control study, 45 patients were divided into two groups: 24 patients in the therapy group (TG) and 21 in the control group (CG). The autoimmune diagnoses were undifferentiated connective tissue disease (9 patients in TG and 12 in CG), Behçet's syndrome (4/TG, 5/CG), mixed connective tissue disease (3/TG, 1/CG), and other diagnoses (8/TG and 3/CG). At start of treatment point, the patients were evaluated with SCL-90-R for distress and psychological symptoms, Life Stressor Checklist-Revised for relevant trauma, and SF-36 for quality of life. SF36 and SCL-90 were repeated at the end of treatment and at 6-month follow-up. RESULTS: Relevant trauma was found in 24/24 TG patients and in 17/21 CG. Eighteen out of twenty-four TG patients exhibited psychiatric comorbidity with 18/21 in the CG. At start of treatment, all patients exhibited high level of distress (GSI > 0.5) and high Depression and Anxiety scores in SCL-90-R. At end of therapy, the TG exhibited greatly improved GSI (p < 0.001), Depression (p < 0.001), and Anxiety (p < 0.001) compared with the GC; SF-36 scores were also much better in the TG, with significant differences ranging from p = 0.002 to p = 0.0004 at end of therapy. These results persisted at the 6-month follow-up. CONCLUSIONS: Tandem-Psychotherapy is effective for improving psychological symptoms and quality of life in autoimmune patients with high levels of distress and relevant psychiatric comorbidity.Key Points• Psychological distress is very high in autoimmune patients, often for previous traumatic experiences.• Psychological support must be both trauma-focused and aimed to improve social functioning.• Quality of life is very much improved by reducing psychological distress.• Tandem-Psychotherapy is feasible because it is contained within a relatively limited time, also for patients with history of trauma.


Assuntos
Doenças Autoimunes/psicologia , Dessensibilização e Reprocessamento através dos Movimentos Oculares/métodos , Hipnose/métodos , Psicoterapia/métodos , Estresse Psicológico/terapia , Adulto , Idoso , Ansiedade/terapia , Estudos de Casos e Controles , Depressão/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Angústia Psicológica , Psicoterapia de Grupo , Qualidade de Vida , Estresse Psicológico/psicologia , Adulto Jovem
8.
Nanomaterials (Basel) ; 10(5)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32354141

RESUMO

Silver-based low-emissivity (low-E) coatings are applied on architectural glazing to cost-effectively reduce heat losses, as they generally consist of dielectric/Ag/dielectric multilayer stacks, where the thin Ag layer reflects long wavelength infrared (IR), while the dielectric layers both protect the Ag and act as an anti-reflective barrier. The architecture of the multilayer stack influences its mechanical properties and it is strongly dependent on the residual stress distribution in the stack. Residual stress evaluation by combining focused ion beam (FIB) milling and digital image correlation (DIC), using the micro-ring core configuration (FIB-DIC), offers micron-scale lateral resolution and provides information about the residual stress variation with depth, i.e., it allows depth profiling for both equibiaxial and non-equibiaxial stress distributions and hence can be effectively used to characterize low-E coatings. In this work, we propose an innovative approach to improve the depth resolution and surface sensitivity for residual stress depth profiling in the case of ultra-thin as-deposited and post-deposition annealed Si3N4/Ag/ZnO low-E coatings, by considering different fractions of area for DIC strain analysis and accordingly developing a unique influence function to maintain the sensitivity of the technique at is maximum during the calculation. Residual stress measurements performed using this novel FIB-DIC approach revealed that the individual Si3N4/ZnO layers in the multilayer stack are under different amounts of compressive stresses. The magnitude and orientation of these stresses changes significantly after heat treatment and provides a clear explanation for the observed differences in terms of scratch critical load. The results show that the proposed FIB-DIC combined-areas approach is a unique method for accurately probing non-equibiaxial residual stresses with nano-scale resolution in thin films, including multilayers.

9.
Br J Haematol ; 146(1): 44-53, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19438486

RESUMO

IGHV mutational status and ZAP-70 or CD38 expression correlate with clinical course in B-cell chronic lymphocytic leukaemia (CLL). The three markers may be discordant in the single case and there is no consensus on their combined use in clinical practise. This multicenter study investigated this issue. Two-hundred and sixty-two Binet stage A patients were studied for the three markers. Sixty patients were profiled with HG-U133A gene expression chips. Disease progression was determined by time from diagnosis to treatment (TTT). The probability of being treatment-free at 3 years was significantly shorter in patients with unmutated IGHV genes (IGHVunmut 66% vs. 93%, chi square of log-rank = 30, P < 0.0001), ZAP-70 positive (ZAP-70pos 73% vs. 96%, chi square of log-rank = 8.2, P = 0.004) or CD38-positive cells (CD38pos 68% vs. 91%, chi square of log-rank = 21, P < 0.0001). Cox multivariate regression analysis showed that the three markers had an independent predictive value for TTT of similar power. A prognostic system based on presence of none (low-risk), one (intermediate-risk) or two or three (high-risk) markers was generated. Based on such criteria, 56%, 23% and 21% of cases were clustered in low (HR = 1), intermediate [HR = 2.8, 95% confidence interval (CI) 2.4-5.8] and high-risk group (HR = 8.0, 95% CI 3.9-16.2). Specific transcriptional patterns were significantly associated with risk groups.


Assuntos
Genes de Cadeia Pesada de Imunoglobulina , Leucemia Linfocítica Crônica de Células B/genética , Mutação , ADP-Ribosil Ciclase 1/análise , Idoso , Biomarcadores Tumorais/análise , Progressão da Doença , Feminino , Perfilação da Expressão Gênica/métodos , Marcadores Genéticos , Humanos , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/metabolismo , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Medição de Risco/métodos , Proteína-Tirosina Quinase ZAP-70/análise
10.
Am J Gastroenterol ; 104(1): 195-217; quiz 194, 218, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19098870

RESUMO

OBJECTIVES: The human leukocyte antigen (HLA) system includes genes involved in graft-vs-host rejection and in immune response. The discovery that HLAs are associated with several diseases led to appealing developments both in basic biomedical research and in clinical medicine, and offered the opportunity to improve the understanding of pathogenesis and classification of diseases, as well as to provide diagnostic and prognostic indicators. The aim of this article is to review the association between HLA alleles and autoimmune digestive disease and its current relationship with modern HLA nomenclature and clinical practice. METHODS: Articles dealing with the association between HLAs and autoimmune digestive disease (including celiac disease, inflammatory bowel disease, autoimmune hepatitis, sclerosing cholangitis and primary biliary cirrhosis) were searched for using Pubmed and SCOPUS databases from earliest records to January 2008. RESULTS: The review has provided two sections. In the first, we explain the basic principles of HLA structure, function, and nomenclature, as an introduction to the second section, which describes current associations between HLA alleles and digestive diseases. The clinical implications of each HLA association are critically discussed. Actually, a clinical role for HLA typing is suggested for only a few conditions, e.g., celiac disease. CONCLUSIONS: The knowledge of current HLA nomenclature and of its association with some digestive diseases such as celiac disease can be useful in clinical practice for diagnostic and prognostic purposes. This can avoid improper HLA typing as well as stressing the need for further studies on other possible clinical applications.


Assuntos
Doenças Autoimunes/imunologia , Doenças do Sistema Digestório/imunologia , Antígenos HLA , Doenças Autoimunes/genética , Doença Celíaca/genética , Doença Celíaca/imunologia , Colangite Esclerosante/genética , Colangite Esclerosante/imunologia , Doenças do Sistema Digestório/genética , Predisposição Genética para Doença , Antígenos HLA/genética , Antígenos HLA/imunologia , Hepatite Autoimune/genética , Hepatite Autoimune/imunologia , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Cirrose Hepática Biliar/genética , Cirrose Hepática Biliar/imunologia
11.
Ann Hematol ; 88(9): 855-61, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19189105

RESUMO

We retrospectively reviewed 139 stage I-II HL patients who were diagnosed and followed up in an Italian northern region (Liguria) from 1995 to 2007, and who received either chemotherapy (CT) alone (mainly doxorubicin, bleomycin, vinblastine, and dacarbazine; ABVD) or a combined modality treatment (chemotherapy + radiotherapy, CT + RT). The two therapeutic groups were comparable for clinical and histologic features. Complete remission rate after CT + RT was higher than what was achieved with CT alone (96% vs. 84%, respectively, p = 0.03). Relapse rate (12%) was the same in both groups and disease-free survival curves were comparable (82% and 83%, p = 0.47). The overall survival of the two therapeutic groups is comparable. No second tumors have been reported among patients receiving chemotherapy alone, whereas a second neoplasia has been diagnosed in four patients (in two cases possibly radiotherapy related) in the CT + RT group (5%, p = 0.09) In conclusion, our retrospective study shows that CT + limited RT is an effective and well-tolerated option for early stage Hodgkin's lymphoma, even if the use of RT is associated with a certain risk of developing a second tumor. However, four to six courses of ABVD can lead to similar, optimal, long-term disease control without exposing patients to the risk of a second neoplasia.


Assuntos
Antineoplásicos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Adulto , Idoso , Terapia Combinada , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/patologia , Doença de Hodgkin/prevenção & controle , Humanos , Itália , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/patologia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
J Colloid Interface Sci ; 531: 451-462, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30053690

RESUMO

HYPOTHESIS: Bolaamphiphiles are characterized by wide polymorphism of their aggregates, due to the connection of the headgroups that renders their investigation very intriguing in several technological applications. Some bolaamphiphiles displaying the triphenylphosphonium motif (TPP-bolaamphiphiles) were previously explored for their ability in crossing the mitochondrial membranes but their colloidal features, which are crucial for the potential development of an effective drug delivery system, were never investigated. EXPERIMENTS: Single chain TPP-bolaamphiphiles, featuring chains of 12, 16, 20 and 30 methylene units, were synthesized and their aggregation features (Krafft point, cac, dimensions, morphology, stability) were investigated by conductivity, dialysis, transmission electron microscopy, Raman spectroscopy, dynamic and dielectrophoretic laser light scattering measurements. FINDINGS: All the TPP-bolaamphiphiles spontaneously self-assemble into vesicles, independently of the chain length. The bolaamphipile with the longest chain forms monodispersed vesicles whereas for the other bolaamphiphiles two distinct populations of vesicles are observed. All vesicles are not equilibrium systems, in particular vesicles formed by the bolaamphiphiles featuring 20 and 30 methylene units result notably stable to dilution thanks to both the tightening of molecular packing at increasing chain length and the progressive reduction of the monomer percentage in U-shaped conformation. These features make these TPP-bolaamphiphiles very attractive as minor components for the development of novel mitochondriotropic liposomes.


Assuntos
Furanos/química , Compostos Organofosforados/química , Piridonas/química , Dimerização , Difusão Dinâmica da Luz , Lipossomos/química , Tamanho da Partícula , Análise Espectral Raman , Eletricidade Estática , Tensoativos/química , Termodinâmica
14.
J Clin Invest ; 113(11): 1651-9, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15173892

RESUMO

The IL-12Rbeta2 gene is expressed in human mature B cell subsets but not in transformed B cell lines. Silencing of this gene may be advantageous to neoplastic B cells. Our objective was to investigate the mechanism(s) and the functional consequence(s) of IL-12Rbeta2 gene silencing in primary B cell tumors and transformed B cell lines. Purified tumor cells from 41 patients with different chronic B cell lymphoproliferative disorders, representing the counterparts of the major mature human B cell subsets, tested negative for IL-12Rbeta2 gene expression. Hypermethylation of a CpG island in the noncoding exon 1 was associated with silencing of this gene in malignant B cells. Treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine restored IL-12Rbeta2 mRNA expression in primary neoplastic B cells that underwent apoptosis following exposure to human recombinant IL-12 (hrIL-12). hrIL-12 inhibited proliferation and increased the apoptotic rate of IL-12Rbeta2-transfected B cell lines in vitro. Finally, hrIL-12 strongly reduced the tumorigenicity of IL-12Rbeta2-transfected Burkitt lymphoma RAJI cells in SCID-NOD mice through antiproliferative and proapoptotic effects, coupled with neoangiogenesis inhibition related to human IFN-gamma-independent induction of hMig/CXCL9. The IL-12Rbeta2 gene acts as tumor suppressor in chronic B cell malignancies, and IL-12 exerts direct antitumor effects on IL-12Rbeta2-expressing neoplastic B cells.


Assuntos
Azacitidina/análogos & derivados , Genes Supressores de Tumor/fisiologia , Leucemia de Células B/genética , Receptores de Interleucina/genética , Animais , Azacitidina/farmacologia , Linfócitos B/metabolismo , Doença Crônica , Metilases de Modificação do DNA/antagonistas & inibidores , Decitabina , Humanos , Interleucina-12/metabolismo , Leucemia de Células B/metabolismo , Transtornos Linfoproliferativos/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Tonsila Palatina/citologia , Tonsila Palatina/metabolismo , Receptores de Interleucina/metabolismo , Receptores de Interleucina-12
15.
Surg Laparosc Endosc Percutan Tech ; 17(3): 175-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17581460

RESUMO

Ultrasound or computed tomography-guided percutaneous lymph nodes biopsy often do not supply sufficient tissue for the histopathologic diagnosis of a lymphoma. Laparoscopic lymph node biopsy (LLB) has the advantage of obtaining the entire lymph node and avoiding the invasivity and all the possible complications of a laparotomy. The aim of the present study is to assess the safety and diagnostic accuracy of the LLB in intra-abdominal lymphoma. Between April 1999 and October 2005, 36 LLB were performed in 35 patients to rule out or to follow the progression of a lymphoma. The clinical outcome and the pathology reports were analyzed retrospectively. A conversion to laparotomy was necessary in 2 cases due to intraoperative difficulties (5.8%). No major postoperative complications or mortality occurred. Mean hospital stay was 2.1 days. In 9 patients, LLB was performed to follow a possible progression of the lymphoma, whereas in 26 patients it was used to establish a diagnosis. Two repeated LLB were necessary to achieve a correct diagnosis in 1 patient. Fourteen patients had non-Hodgkin lymphoma, 6 patients had Hodgkin lymphoma, 9 patients presented an infiltration by primitive or metastatic tumors, and 7 patients had benign lymphadenopathy. In 97% of the cases, LLB supplied the necessary information for the correct diagnosis, classification, and subsequent therapeutic decisions. In conclusion, LLB is a safe and effective procedure. Its diagnostic accuracy is superior to percutaneous techniques. LLB can be proposed as the procedure of choice to sample deep lymphatic tissues in patients with intra-abdominal lymphadenopathy at a very low morbidity rate and as an outpatient procedure in selected cases.


Assuntos
Neoplasias Abdominais/patologia , Biópsia/métodos , Laparoscopia , Linfonodos/patologia , Linfoma/patologia , Progressão da Doença , Feminino , Doença de Hodgkin/patologia , Humanos , Laparotomia , Tempo de Internação , Doenças Linfáticas/patologia , Metástase Linfática/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Complicações Pós-Operatórias , Estudos Retrospectivos , Segurança
16.
Hum Mutat ; 27(4): 330-6, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16453338

RESUMO

The inherited deficiency of the von Willebrand factor-cleaving protease ADAMTS13 is associated with rare forms of thrombotic thrombocytopenic purpura (TTP). We investigated a woman with a family history of chronic recurrent TTP and undetectable plasma levels of ADAMTS13 activity. Genetic analysis revealed two missense mutations in the heterozygous state: p.Val88Met substitution in the metalloprotease domain and p.Gly1239Val substitution in the first CUB domain of ADAMTS13. To explore the mechanism of ADAMTS13 deficiency in this patient, the wild type (WT; ADAMT13(WT)) and each mutant construct (ADAMTS13(Val88Met), ADAMTS13(Gly1239Val)) were transiently expressed in HEK 293 and COS-7 cells. To recapitulate the compound heterozygous state of the patient, both mutant ADAMTS13 proteins were also expressed together. The p.Val88Met mutation led to a defect of secretion of the protease associated with a reduction of enzymatic activity, the p.Gly1239Val mutation led to a secretion defect causing intracellular accumulation of the protease. The mechanistic effects of the mutations were further explored by means of differential immunofluorescence, that demonstrated an homogeneous distribution of ADAMTS13(WT) in the Cis-Golgi and endoplasmic reticulum (ER) compartments, a reduction of ADAMTS13(Val88Met) in both compartments, while ADAMTS13(Gly1239Val) failed to reach the Cis-Golgi compartment and remained in the ER.


Assuntos
Proteínas ADAM/deficiência , Proteínas ADAM/genética , Mutação/genética , Proteína ADAMTS13 , Adulto , Animais , Células COS , Chlorocebus aethiops , Meios de Cultivo Condicionados , Feminino , Imunofluorescência , Humanos , Proteínas Recombinantes/genética
17.
Thromb Haemost ; 96(4): 454-64, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17003922

RESUMO

Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by microvascular thrombosis, often associated with deficiency of the vonWillebrand factor (VWF) cleaving protease ADAMTS13. We investigated the spectrum of ADAMTS13 gene mutations in patients with TTP and congenital ADAMTS13 deficiency to establish the consequences on ADAMTS13 processing and activity. We describe five missense (V88M, G1239V, R1060W, R1123C and R1219W), 1 nonsense (W1016Stop) and 1 insertion (82_83insT) mutations. In two patients no mutation was identified despite undetectable protease activity. Expression in HEK293 mammalian cells (V88M, G1239V, R1123C and R1219W) documented that three missense mutants were not secreted, whereas theV88M was secreted at low levels and with reduced activity. We also provide evidence that impaired secretion of ADAMTS13 mutants observed in vitro translates into severely reduced ADAMTS13 antigen levels in patients in vivo. To evaluate whether the small amounts of mutant protease present in the circulation of patients had VWF cleaving activity, WT and mutant rADAMTS13 were stably expressed in Drosophila S2 cells under the influence of the Drosophila BiP protein signal sequence, which allows protein secretion. Drosophila expression system showed a 40-60% protease activity in the mutants. Several single nucleotide polymorphisms (SNPs) within exons and intron boundaries were found in patients, suggesting that the interplay of SNPs could at least in part account for ADAMTS13 functional abnormalities in patients without mutations. In conclusion, defective secretion and impaired activity of the mutants concur to determine an almost complete deficiency of ADAMTS13 activity in patients with a homozygous or two heterozygous ADAMTS13 mutations.


Assuntos
Proteínas ADAM/metabolismo , Púrpura Trombocitopênica Trombótica/enzimologia , Fator de von Willebrand/metabolismo , Proteínas ADAM/genética , Proteínas ADAM/imunologia , Proteína ADAMTS13 , Animais , Antígenos/sangue , Western Blotting , Linhagem Celular , Códon sem Sentido , Humanos , Mutação de Sentido Incorreto , Linhagem , Polimorfismo de Nucleotídeo Único , Púrpura Trombocitopênica Trombótica/genética , Púrpura Trombocitopênica Trombótica/imunologia , Transfecção
18.
Anesth Analg ; 103(2): 309-11, table of contents, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16861409

RESUMO

Glanzmann's thrombasthenia is a congenital hemorrhagic disorder transmitted as an autosomal recessive trait and characterized by altered production and/or assembly of the platelet membrane glycoprotein IIb/IIIa receptor. We describe the perioperative management of a heterozygous carrier of Glanzmann's thrombasthenia submitted to cardiac surgery with cardiopulmonary bypass and the case was complicated by early excessive postoperative bleeding.


Assuntos
Ponte Cardiopulmonar , Ponte de Artéria Coronária , Trombastenia/complicações , Idoso , Heterozigoto , Humanos , Masculino , Hemorragia Pós-Operatória/etiologia , Ácido Tranexâmico/uso terapêutico
19.
Stroke ; 36(7): 1490-4, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15947270

RESUMO

BACKGROUND AND PURPOSE: Because thromboembolic events are frequently observed in primary antiphospholipid syndrome (PAPS), we assessed the risk factors for new thrombotic episodes. METHODS: Fifty-six PAPS patients (mean age, 37+/-10 years) were prospectively studied for 5 years. The preliminary Sapporo classification criteria for antiphospholipid syndrome (APS; a medium-high anticardiolipin antibody [aCL] titer and/or a positive lupus anticoagulant [LA] test in the presence of vascular thrombosis and/or pregnancy morbidity) were used to confirm the diagnosis. Thrombotic episodes or pregnancy losses before a diagnosis of PAPS were considered events, and any new disease manifestation other than thrombocytopenia was considered a recurrent event. Only patients with objectively verified thrombotic events were included in the study. RESULTS: Twenty-one new thrombotic events were observed in 15 subjects (26.8%), including 3 (5.4%) who died during the follow-up. The patients with IgG aCL levels of >40 IgG phospholipid unit (GPL-U) showed a higher incidence of new thrombotic events (43.3%) than those with levels of < or =40 GPL-U (7.7%). Univariate analysis identified a history of recurrent clinical events (P=0.004), a highly positive aCL titer (P=0.007), and the presence of cardiac abnormalities (P=0.036) as significant risk factors for new thrombotic events. A multivariate regression model confirmed that an IgG aCL titer of >40 GPL-U was an independent risk factor for thrombosis (odds ratio, 9.17; 95% confidence interval, 1.83 to 46.05). CONCLUSIONS: A high IgG aCL titer is the strongest predictor of new thrombotic events in PAPS patients.


Assuntos
Síndrome Antifosfolipídica/patologia , Trombose/patologia , Aborto Espontâneo , Adulto , Idoso , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/diagnóstico , Estudos de Coortes , Ecocardiografia/métodos , Feminino , Seguimentos , Humanos , Imunoglobulina G/química , Inibidor de Coagulação do Lúpus/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Gravidez , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Trombocitopenia/metabolismo , Trombose/diagnóstico , Fatores de Tempo
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