RESUMO
OBJECTIVES: Healthcare products (HP) have a significant carbon footprint that must be included by regulation in the facility's purchasing policy. A national overview of the inclusion of environmental criteria (EC) in the public procurement (PP) of HP in hospitals has been carried out. METHODS: Thirty EC were identified in the literature. Two questionnaires were proposed: (i) for buyers that analyze the level of "importance" and "ease of application" for public tenders (PT), and (ii) for suppliers that declare their commitments and evidence. RESULTS: Six regional buyers and 28 suppliers participated. Buyers recognize the "importance" of sustainable development (SD) but are more reticent about the "applicability" of EC in PT. The environmental rating remains low: on average 4.38 (0.25-10.00) % of the total rating. Only 12 EC are integrated within some PT. Suppliers report a high and diversified commitment to SD: 18 suppliers sent 474 evidence. Buyers and suppliers converge on the optimization of primary packaging and the establishment of a minimum order or delivery group. CONCLUSIONS: Since the efficiency of PP is inevitable, EC that combines SD and savings should be prioritized. The integration of additional EC, simple and easily documented, allowing cost containment for both suppliers and buyers, is possible to promote sustainable purchasing.
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Pegada de Carbono , Custos de Medicamentos , Equipamentos e Provisões , Controle de Custos , Equipamentos e Provisões/economia , França , HumanosRESUMO
OBJECTIVE: To preoperatively reduce tumour size in patients with locally advanced and/or non-resectable squamous cell carcinoma with induction chemotherapy in order to achieve surgical excision with clear margins and preserve quality of life. METHODOLOGY: In this study, 16 patients with locally advanced and/or non-resectable squamous cell carcinoma underwent induction chemotherapy with docetaxel, cisplatin, and 5-fluorouricil or paclitaxel, carboplatin, and cetuximab. RESULTS: Over 80% of patients responded to induction chemotherapy. Histological examination of the 14 surgical specimens showed a total absence of residual cancer cells in 37.5% of cases. CONCLUSION: Concurrent radiation and chemotherapy is the standard treatment for locally advanced head and neck squamous cell carcinoma; however, induction chemotherapy may be beneficial in select patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Orofaríngeas/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/patologia , Cetuximab/administração & dosagem , Cisplatino/administração & dosagem , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Orofaríngeas/patologia , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here we report our recommendations regarding the use of immunosuppressive treatment in the prevention of graft versus host disease: report by the SFGM-TC.
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Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Células-Tronco , França , Humanos , Transplante de Células-Tronco/métodos , Transplante de Células-Tronco/normasRESUMO
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of pre-transplant donor's cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test.
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Infecções por Citomegalovirus/diagnóstico , Seleção do Doador/normas , Infecções por Vírus Epstein-Barr/diagnóstico , Transplante de Células-Tronco Hematopoéticas/normas , Achados Incidentais , Sífilis/diagnóstico , Toxoplasmose/diagnóstico , Doadores de Sangue , Consenso , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/sangue , Infecções por Vírus Epstein-Barr/sangue , França , Conhecimentos, Atitudes e Prática em Saúde , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imunoglobulina M/sangue , Sífilis/sangue , Sífilis/imunologia , Toxoplasma/isolamento & purificação , Toxoplasmose/sangue , Transplante HomólogoRESUMO
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of common issues related to the donor: pre-transplant pregnancy and monoclonal gammopathy.
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Doadores de Sangue , Seleção do Doador/normas , Conhecimentos, Atitudes e Prática em Saúde , Transplante de Células-Tronco Hematopoéticas/normas , Achados Incidentais , Paraproteinemias/diagnóstico , Testes de Gravidez , Consenso , Feminino , Idade Gestacional , Humanos , Paraproteinemias/sangue , Gravidez/sangue , Complicações na Gravidez/sangue , Complicações na Gravidez/prevenção & controleRESUMO
Major-histocompatibility-complex (MHC) proteins are used to display, on the surface of a cell, peptides derived from foreign material - such as a virus - that is infecting that cell. Cytotoxic T lymphocytes then recognize and kill the infected cell. The HIV-1 Nef protein downregulates the cell-surface expression of class I MHC proteins, and probably thereby promotes immune evasion by HIV-1. In the presence of Nef, class I MHC molecules are relocalized from the cell surface to the trans-Golgi network (TGN) through as-yet-unknown mechanisms. Here we show that Nef-induced downregulation of MHC-I expression and MHC-I targeting to the TGN require the binding of Nef to PACS-1, a molecule that controls the TGN localization of the cellular protein furin. This interaction is dependent on Nef's cluster of acidic amino acids. A chimaeric integral membrane protein containing Nef as its cytoplasmic domain localizes to the TGN after internalization, in an acidic-cluster- and PACS-1-dependent manner. These results support a model in which Nef relocalizes MHC-I by acting as a connector between MHC-I's cytoplasmic tail and the PACS-1-dependent protein-sorting pathway.
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Capsídeo/metabolismo , Proteínas de Transporte , Produtos do Gene nef/metabolismo , HIV-1/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Animais , Antígenos CD4/metabolismo , Capsídeo/antagonistas & inibidores , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Endocitose/efeitos dos fármacos , Endocitose/genética , Furina , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Produtos do Gene nef/farmacologia , Complexo de Golgi/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Melanoma/metabolismo , Melanoma/patologia , Proteínas de Membrana/metabolismo , Oligonucleotídeos Antissenso/farmacologia , Estrutura Terciária de Proteína/genética , Ratos , Receptor IGF Tipo 2/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Subtilisinas/metabolismo , Transfecção , Proteínas de Transporte Vesicular , Produtos do Gene nef do Vírus da Imunodeficiência HumanaRESUMO
Studying the genetic basis of gene expression and chromatin organization is key to characterizing the effect of genetic variability on the function and structure of the human genome. Here we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression, and genetic variants across 317 individuals and two cell types. We show that variability in regulatory activity is structured at the intra- and interchromosomal levels within 12,583 cis-regulatory domains and 30 trans-regulatory hubs that highly reflect the local (that is, topologically associating domains) and global (that is, open and closed chromatin compartments) nuclear chromatin organization. These structures delimit cell type-specific regulatory networks that control gene expression and coexpression and mediate the genetic effects of cis- and trans-acting regulatory variants on genes.
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Cromatina/metabolismo , Regulação da Expressão Gênica , Cromatina/química , Variação Genética , Genoma Humano , Humanos , Locos de Características Quantitativas , Elementos Reguladores de TranscriçãoRESUMO
INTRODUCTION: Giant cell arteritis (GCA) is a granulomatous vasculitis of the large and medium size vessels with a remarkable sensitivity to corticosteroids, although it may be dependent to therapy. In rare cases, a vasculitis of the medium or small-size vessels may mimic, be associated to, or follow GCA. We report a case of GCA dependent to corticosteroids that was followed five years after diagnosis by an alveolar hemorrhage leading to the diagnosis of a possible Wegener's granulomatosis. EXEGESIS: A 70-year-old man had a diagnosis of GCA fulfilling the ACR criteria in 1999. Temporal artery biopsy revealed a typical histological pattern. The initial response to corticosteroids was excellent, but the patient became dependent to corticosteroids, so he was given methotrexate from 2002. Severe alveolar haemorrhage occurred in December 2004, leading to the diagnosis of possible ANCA positive, anti-proteinase 3 positive Wegener's granulomatosis. CONCLUSION: ANCA-positive vasculitis may complicate the course of GCA. This evolution should be rapidly recognized, because its treatment differs to that of GCA.
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Anticorpos Anticitoplasma de Neutrófilos , Arterite de Células Gigantes , Granulomatose com Poliangiite/diagnóstico , Hemorragia/etiologia , Pneumopatias/etiologia , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Idoso , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Biópsia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Seguimentos , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/patologia , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/complicações , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Troca Plasmática , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Alvéolos Pulmonares , Radiografia Torácica , Artérias Temporais/patologia , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To evaluate the outcome of patients treated for soft tissue sarcoma using three different post-operative radiotherapy schedules. METHODS AND MATERIALS: Between 1990 and 2003, 89 patients (median age 50.8 years) presenting with soft tissue sarcoma (located to the limbs for 66 of them) underwent post-conservative-surgery radiotherapy. Pathology was liposarcoma in 35 cases and 54 others tumors. Tumors grades (FNCLCC classification) were 1, 2, 3 or unknown in 29, 32, 19 and 9 cases, respectively. Surgery was considered as complete in 68 patients. Irradiation was normofractionated (NF) in 62 cases, hyperfractionated (BF) in 19 cases and hypofractionated (HF) in 8 cases. For all the patients, median delivered dose was 61 Gy [34-76 Gy]. RESULTS: Median follow-up of alive patients was 73,8 months [3-184]. Five-year local control (LC) and overall survival (OS) rates were 85.5 and 71.2% respectively. According to multifactorial analysis, favourable prognostic factors were for local control, complete surgery (P=0.0075) and for overall survival, complete surgery (P=0.0267), grade 1 tumor (P=0.012) and absence of distant recurrence (P=0.0488). There was no statistical evidence of difference for the five-year LC and OS rates between the patients who received NF, BF or HF. There were few complications and there were comparable in the three groups. CONCLUSIONS: This retrospective serie showed similar results for all the schedules. There is no evidence to recommend bifractionation. Hypofractionation should be used only in selected patients with poor performans status.
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Sarcoma/radioterapia , Sarcoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Sarcoma/mortalidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: Pemphigus vulgaris frequently requires corticoids and immuno-suppressive drugs. The disease and the side effects of the drugs severely affect the quality of life, and sometime the vital prognosis of the patients. Other treatments than corticosteroids and immunosuppressive drugs are needed. EXEGESIS: We report 2 additional cases of pemphigus vulgaris uncontrolled by corticoids and immuno-suppressive drugs that responded spectacularly to rituximab. One patient had a recently onset disease, that was active despite 1,5 mg/kg/day prednisone and 1,5 g/day mycophenolate. She had a complete remission during 15 months after rituximab treatment. At relapse, another rituximab cycle led to a prompt remission. The other patient had longstanding pemphigus vulgaris complicated by cutaneous infections on prednisone (20 mg/d), immunosuppressive drugs and intravenous immune globulins. She had a prompt and complete remission after rituximab. CONCLUSION: Rituximab seems to be a promising drug for refractory pemphigus vulgaris. The benefit to risk ratio of this drug in this new indication must be precisely documented.
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Anticorpos Monoclonais/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pênfigo/tratamento farmacológico , Anticorpos Monoclonais Murinos , Feminino , Humanos , Pessoa de Meia-Idade , Indução de Remissão , RituximabRESUMO
The marine dinophycean genus Azadinium has been identified as the primary source of azaspiracids (AZA), a group of lipophilic phycotoxins known to accumulate in shellfish. Blooms of Azadinium in the southern Atlantic off Argentina have been described from the 1990s, but due to a lack of cultures, the diversity of South-Atlantic Azadinium has not yet been fully explored and their toxin production potential is completely unknown. During a spring 2010 research cruise covering the El Rincón (ER) estuarine system (North Patagonian coast, Argentina, Southwestern Atlantic) a search was conducted for the presence of Azadinium. Although neither Azadinium cells nor AZA in field plankton samples were detected, 10 clonal strains of Azadinium poporum were successfuly established by incubation of sediment samples. Argentinean A. poporum were more variable in size and shape than the type description but conformed to it by the presence of multiple pyrenoids with starch sheath, in plate pattern and arrangement, and in the position of the ventral pore located on the left side of the pore plate. In contrast to all previous description of A. poporum, isolates of the Argentinean A. poporum possessed a distinct field of pores on the second antapical plate. Conspecificity of the Argentinean isolates with A. poporum was confirmed by molecular phylogeny of concatenated ITS and LSU rDNA sequences, where all Argentinean isolates together with some Chinese A. poporum strains formed a well-supported ribotype clade within A. poporum. All isolates produced AZA with the same profile, consisting of AZA-2 as the major compound and, to a lesser extent, its phosphated form. This is the first report of a phosphated marine algal toxin. This first confirmation of the presence of AZA producing Azadinium in the Argentinean coastal area underlines the risk of AZA shellfish contamination episodes in the Southwestern Atlantic region.
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PURPOSE: To evaluate the activity and the toxicity of the combination of cisplatin (CDDP)/recombinant interleukin-2 (rIL-2) and interferon alfa-2a (IFN alpha) in disseminated malignant melanoma (DMM). PATIENTS AND METHODS: Between December 1990 and March 1992, 39 patients with biopsy-proven metastatic malignant melanoma (MM), bidimensionally measurable lesions and an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2 entered this protocol. Seventy-nine percent had received previous chemotherapy including platinum complex (15%) and alpha interferon (44%). They received CDDP (100 mg/m2 on day 0) followed by IL-2 18.10(6) IU/m2/d continuous intravenous (IV) infusion from day 3 to day 6 and from day 17 to day 21. The cycle was repeated on day 28. Subcutaneous IFN alpha 9.10(6) IU three times weekly was administered throughout the treatment period. From day 66 or 94, patients were administered a maintenance cycle with CDDP 100 mg/m2, subcutaneous IL-2 5.10(6) IU/m2/d from day 15 to day 19 and from day 22 to day 26 and IFN alpha 9.10(6) IU three times weekly repeated every 5 weeks (maximum four cycles). RESULTS: Among 39 assessable patients, five patients achieved complete responses (CRs). Sixteen patients had partial responses (PRs). The overall objective response rate was 53.8%. The number of metastatic sites was the only response-predictive factor. Toxicity was manageable in a routine patient setting and there was no life-threatening toxicity. CONCLUSION: These results seem to indicate a possible synergy between CDDP/rIL-2 and IFN alpha in MM.
Assuntos
Cisplatino/uso terapêutico , Interferon-alfa/uso terapêutico , Interleucina-2/uso terapêutico , Melanoma/terapia , Adulto , Idoso , Terapia Combinada/efeitos adversos , Feminino , Humanos , Imunoterapia/métodos , Interferon alfa-2 , Masculino , Melanoma/tratamento farmacológico , Melanoma/secundário , Pessoa de Meia-Idade , Proteínas Recombinantes , Indução de Remissão , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS: A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS: Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION: This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/patologia , Compostos Organoplatínicos/uso terapêutico , Adenocarcinoma/mortalidade , Idoso , Antineoplásicos/efeitos adversos , Neoplasias Colorretais/mortalidade , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Taxa de SobrevidaRESUMO
PURPOSE: To evaluate an intensive concomitant chemoradiotherapy protocol of conventional radiotherapy with intermittent cisplatin (CDDP) and continuous-infusion fluorouracil (5-FU) in unresectable, locally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Fifty-seven patients with unresectable stage IV MO disease (International Union Against Cancer [UICC]/American Joint Committee on Cancer [AJCC], 1987) received radiotherapy 70 Gy followed by CDDP 80 mg/m2 and 5-FU 300 mg/m2/d. Response was assessed 2 months after treatment completion. RESULTS: Thirty patients (52%) received the full treatment schedule; 53 (93%) received full-dose radiotherapy, while 48 (84%) were given at least 75% of the planned chemotherapy doses. Severe mucositis (World Health Organization [WHO]) grade 3 to 4 was the limiting toxicity and was seen in 79% of patients. The median time for mucositis resolution was 8 weeks. Other toxicities were generally manageable, but there were four treatment related deaths (7%). Fifty patients were assessable for activity, with an overall response rate of 70% (95% confidence interval [CI], 58% to 82%). Complete response (CR) and partial response (PR) rates were 42% and 28%, respectively. CONCLUSION: This simultaneous combined-modality regimen was feasible at the cost of severe mucosal toxicity, which required hospitalization with nutritional, parenteral, and hydroelectrolytic support. The high response rate achieved (70%) did not translate into improved survival, probably due to patient eligibility. The likelihood of cure of this high-tumoral-volume patient population remains low (approximately 10%), despite the association of two therapeutic modalities at full standard therapeutic intensity.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cooperação do Paciente , Prognóstico , Radioterapia Adjuvante , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
Abscisic acid (ABA) is a plant hormone involved in the control of a wide range of physiological processes, including adaptation to environmental stress and seed development. In higher plants ABA is a breakdown product of xanthophyll carotenoids (C40) via the C15 intermediate xanthoxin. The ABA2 gene of Nicotiana plumbaginifolia encodes zeaxanthin epoxidase, which catalyzes the conversion of zeaxanthin to violaxanthin. In this study we analyzed steady-state levels of ABA2 mRNA in N. plumbaginifolia. The ABA2 mRNA accumulated in all plant organs, but transcript levels were found to be higher in aerial parts (stems and leaves) than in roots and seeds. In leaves ABA2 mRNA accumulation displayed a day/night cycle; however, the ABA2 protein level remained constant. In roots no diurnal fluctuation in mRNA levels was observed. In seeds the ABA2 mRNA level peaked around the middle of development, when ABA content has been shown to increase in many species. In conditions of drought stress, ABA levels increased in both leaves and roots. A concomitant accumulation of ABA2 mRNA was observed in roots but not in leaves. These results are discussed in relation to the role of zeaxanthin epoxidase both in the xanthophyll cycle and in the synthesis of ABA precursors.
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We evaluated the predictive value of a tumor's HER-2 status for chemotherapy response in the neoadjuvant setting and the effect of anthracycline dose intensity on this predictive value. HER-2 status was evaluated by immunochemistry on microbiopsy before neoadjuvant chemotherapy (monoclonal antibody CB-11; Novocastra) in 39 patients (group A) treated with FEC50 (500 mg/m(2) 5-fluorouracil, 50 mg/m(2) epirubicin, and 500 mg/m(2) cyclophosphamide) and 40 patients (group B) treated with FEC100 (500 mg/m(2) 5-fluorouracil, 100 mg/m(2) epirubicin, and 500 mg/m(2) cyclophosphamide). All tumors were stage II or noninflammatory stage III adenocarcinoma. Overall response rate (OR) was evaluated through ultrasound and mammographic measurements. Pathological complete response was evaluated by tumor excision and axillary node resection after six cycles of chemotherapy. Patient and tumor characteristics (age, tumor size, clinical nodal status, SBR grade, hormonal receptor status, and HER-2 expression) were similar in the two groups. In univariate analyses, anthracycline dose was the only factor predictive of response (OR = 61.5% with FEC50; OR = 82.5% with FEC100; P = 0.038). When anthracycline dose was correlated with HER-2 status, an OR of 73.9% was demonstrated in HER-2- tumors (tumors without HER-2 overexpression), and an OR of 12.5% was demonstrated in HER-2+ tumors (tumors with HER-2 with overexpression) in group A. In group B, an OR of 69.5% was demonstrated in HER-2- tumors, and an OR of 100% was demonstrated in HER-2+ tumors. There was no difference in OR for HER-2- tumors treated with FEC50 or FEC100 (P = 0.74). On the other hand, erbB-2+ tumors treated with FEC100 had a significantly better OR than HER-2+ tumors treated with FEC50 (P = 0.0003). In a multivariate analysis, the most powerful predictive factor of OR was a conditional variable associating anthracycline dose with HER-2 status. Low-dose anthracycline and HER-2+ predicted a poor OR, low- or high-dose anthracycline and HER-2- predicted an intermediate OR, and high-dose anthracycline and HER-2+ predicted a high OR. Our results merit additional studies, given the possibility for choosing anthracycline dose according to a tumor's HER-2 status.
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Adjuvantes Imunológicos/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/biossíntese , Resultado do Tratamento , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Epirubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Análise MultivariadaRESUMO
The involvement of interleukin (IL-) 6 in malignant disease has been investigated in a variety of different malignancies. To evaluate whether serum IL-6 is a useful disease marker in metastatic malignant melanoma (MMM), we studied the time course of endogenous IL-6 secretion in 41 patients treated with cisplatinum, IL-2, and IFN-alpha. Furthermore, the relationship of endogenous IL-6 concentrations to the tumor burden and/or the clinical response was also evaluated. The baseline serum IL-6 levels were significantly higher in patients with MMM than in the control group (P = 0.002). When tumor burden was taken into consideration, we found that IL-6 levels were higher in patients with high tumor burden than in patients with low tumor burden. During treatment in the whole patient population, a higher serum IL-6 level was observed in nonresponding as compared to responding patients at days 7 (P = 0.0005), 21 (P = 0.002), and 35 (P = 0.009). The follow-up of serum IL-6 in patients with MMM according to the tumor burden and clinical response demonstrated that: (a) IL-6 levels were significantly higher at days 7 and 21 in patients with high tumor burden as compared to those with low tumor burden; and (b) IL-6 levels remain significantly higher in nonresponding patients as compared to responding patients regardless of the tumor burden. From these results, we can conclude that endogenous IL-6 may play a role in the failure of IL-2 therapy in such patients, since the very early IL-6 increase is correlated with the tumor mass and nonresponse to biochemotherapy. Therefore, it seems that the early detection of endogenous IL-6 may represent valuable information for monitoring the response to biochemotherapy in patients with MMM.
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Interleucina-6/sangue , Melanoma/sangue , Melanoma/secundário , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
The species of the Byrsonima genus (Malpighiaceae) have been used in folk medicine to treat gastrointestinal disorders, asthma and skin infections. In this study, the total phenolic content, antioxidant activity and phytochemical screening were carried out in polar extracts of Byrsonima coccolobifolia, Byrsonima verbascifolia and Byrsonima intermedia. The presence of tannins and flavonoids in the samples and high phenols content was observed. B. coccolobifolia and B. intermedia species showed the best results of antioxidant action. It was analysed the correlation between the methods, and there was a great correlation between phenolic content and antioxidant assay, showing that the phenolic substances contribute to the antioxidant activities of these plants.
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Antioxidantes/química , Flavonoides/química , Malpighiaceae/química , Fenóis/química , Taninos/química , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
The gene CLPT1 (Colletotrichum lindemuthianum Protein Transport 1) encoding a Rab/GTPase was isolated from the filamentous fungus Colletotrichum lindemuthianum, the causal agent of bean anthracnose. At the amino acid level, CLPT1 shows between 54 and 80% identity to SEC4-like proteins, a class of molecules required for intracellular vesicular transport in yeasts. In particular, typical SEC4 domains involved in nucleotide binding and membrane attachment are present in the CLPT1 sequence. Functional identity of CLPT1 with SEC4 was confirmed by complementation of the Saccharomyces cerevisiae sec4-8 mutation. This is the first report of a gene involved in the control of intracellular vesicular trafficking in a phytopathogenic fungus. RNA blot analyses of CLPT1 expression were performed during in vitro growth of the fungus on synthetic media containing glucose or pectin, as single carbon source. The accumulation of CLPT1 mRNA was strongly increased on pectin, a plant cell wall polysaccharide that induces the production of extracellular pectinases, whereas the level of CLPT1 mRNA was below the detection threshold on glucose. These results suggest that CLPT1 is mainly involved in protein secretion and that the production of extracellular enzymes potentially involved in pathogenesis in filamentous fungi is sustained by induction of the genes involved in the secretory machinery.
Assuntos
Colletotrichum/genética , Proteínas Fúngicas , Proteínas rab de Ligação ao GTP/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Colletotrichum/efeitos dos fármacos , Colletotrichum/enzimologia , DNA Fúngico/química , DNA Fúngico/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Dados de Sequência Molecular , Pectinas/farmacologia , Doenças das Plantas/microbiologia , Poligalacturonase/genética , Proteínas de Saccharomyces cerevisiae , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy that may lead to quadriparesis, ventilatory failure, and autonomic dysfunction. While significant mortality due to ventilatory failure has been associated with this syndrome, this complication can now be readily managed. However, an estimated mortality of 5% to 20% remains attributable to medical complications (pulmonary embolus, sepsis) and to acute cardiovascular collapse due to autonomic failure. In this report, detailed sequential changes in hemodynamic parameters, as measured by Swan-Ganz catheter, associated with severe autonomic cardiovascular instability in a patient with GBS are described. Knowledge of changes in these hemodynamic parameters led to optimal therapy. Long-term Swan-Ganz monitoring in an intensive care setting may dramatically benefit the critically ill patient with GBS and cardiovascular autonomic dysfunction, and may help to eliminate the residual morbidity and mortality associated with this disease.