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1.
Yeast ; 37(1): 173-185, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31770454

RESUMO

Cation/proton antiporters play a major role in the control of cytosolic ion concentrations in prokaryotes and eukaryotes organisms. In yeast, we previously demonstrated that Vnx1p is a vacuolar monovalent cation/H+ exchanger showing Na+ /H+ and K+ /H+ antiporter activity. We have also shown that disruption of VNX1 results in an almost complete abolishment of vacuolar Na+ /H+ exchange, but yeast cells overexpressing the complete protein do not show improved salinity tolerance. In this study, we have identified an autoinhibitory N-terminal domain and have engineered a constitutively activated version of Vnx1p, by removing this domain. Contrary to the wild type protein, the activated protein has a pronounced effect on yeast salt tolerance and vacuolar pH. Expression of this truncated VNX1 gene also improves Arabidopsis salt tolerance and increases Na+ and K+ accumulation of salt grown plants thus suggesting a biotechnological potential of activated Vnx1p to improve salt tolerance of crop plants.


Assuntos
Arabidopsis/fisiologia , Deleção de Genes , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/fisiologia , Tolerância ao Sal/genética , Trocadores de Sódio-Hidrogênio/genética , Arabidopsis/genética , Plantas Geneticamente Modificadas/fisiologia , Potássio/metabolismo , Saccharomyces cerevisiae/genética , Sódio/metabolismo , Vacúolos/metabolismo
2.
Lupus ; 25(6): 582-92, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26424128

RESUMO

OBJECTIVE: B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) signaling pathways regulate B-cell survival through interactions with their receptors BAFF-R, TACI and BCMA. We evaluated the association of these ligands/receptors on B-cell subsets according to clinical manifestations of systemic lupus erythematosus (SLE). METHODS: BAFF and APRIL serum concentrations were measured in 30 SLE patients by enzyme-linked immunosorbent assay. The BAFF-R, TACI and BCMA expression was analyzed on each B cell subset (CD19 + CD27-CD38-/ + naïve; CD19 + CD27 + CD38-/ + memory; CD19 + CD27-CD38 + + immature and CD19 + CD27 + CD38 + + plasma cells) by flow cytometry, and compared among patients with different clinical manifestations as well as healthy controls (HCs). RESULTS: Serum BAFF and APRIL levels were high in SLE patients and correlated with the Mex-SLEDAI disease activity index (r = 0.584; p = 0.001 and r = 0.456; p = 0.011, respectively). The SLE patients showed an increased proportion of memory and plasma B cells (p < 0.05). BAFF-R, TACI and BCMA expression in SLE patients was decreased in almost all B cell subsets compared to HCs (p < 0.05). A lower BCMA expression was associated with severe disease activity, glomerulonephritis, serositis and hemolytic anemia (p < 0.01). BCMA expression showed a negative correlation with Mex-SLEDAI score (r = -0.494, p = 0.006). CONCLUSIONS: Decreased BCMA expression on peripheral B cells according to severe disease activity suggests that BCMA plays an important regulating role in B-cell hyperactivity and immune tolerance homeostasis in SLE patients.


Assuntos
Fator Ativador de Células B/sangue , Subpopulações de Linfócitos B/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Adolescente , Adulto , Idoso , Receptor do Fator Ativador de Células B/genética , Antígeno de Maturação de Linfócitos B/genética , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Tolerância Imunológica , Lúpus Eritematoso Sistêmico/imunologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Proteína Transmembrana Ativadora e Interagente do CAML/genética , Adulto Jovem
3.
Parasitology ; 142(8): 1115-29, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25823476

RESUMO

The in vitro leishmanicidal activity of a series of imidazole-containing phthalazine derivatives 1-4 was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, and their cytotoxicity on J774·2 macrophage cells was also measured. All compounds tested showed selectivity indexes higher than that of the reference drug glucantime for the three Leishmania species, and the less bulky monoalkylamino substituted derivatives 2 and 4 were clearly more effective than their bisalkylamino substituted counterparts 1 and 3. Both infection rate measures and ultrastructural alterations studies confirmed that 2 and 4 were highly leishmanicidal and induced extensive parasite cell damage. Modifications to the excretion products of parasites treated with 2 and 4 were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds 2 and 4 were potent inhibitors of iron superoxide dismutase enzyme (Fe-SOD) in the three species considered, whereas their impact on human CuZn-SOD was low. Molecular modelling suggests that 2 and 4 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the antioxidant features of the enzyme.


Assuntos
Inibidores Enzimáticos/farmacologia , Imidazóis/farmacologia , Leishmania/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Ftalazinas/farmacologia , Superóxido Dismutase/antagonistas & inibidores , Animais , Feminino , Humanos , Leishmania/enzimologia , Leishmania braziliensis/efeitos dos fármacos , Leishmania braziliensis/enzimologia , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/enzimologia , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/enzimologia , Leishmaniose/parasitologia , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Macrófagos , Camundongos Endogâmicos BALB C , Oxirredução , Superóxido Dismutase/metabolismo
4.
Phys Rev Lett ; 113(26): 267202, 2014 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-25615378

RESUMO

We demonstrate that magnetic properties of ultrathin Co films adjacent to Gd2O3 gate oxides can be directly manipulated by voltage. The Co films can be reversibly changed from an optimally oxidized state with a strong perpendicular magnetic anisotropy to a metallic state with an in-plane magnetic anisotropy or to an oxidized state with nearly zero magnetization, depending on the polarity and time duration of the applied electric fields. Consequently, an unprecedentedly large change of magnetic anisotropy energy up to 0.73 erg/cm(2) has been realized in a nonvolatile manner using gate voltages of only a few volts. These results open a new route to achieve ultralow energy magnetization manipulation in spintronic devices.

5.
Parasitology ; 141(8): 1031-43, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24636142

RESUMO

The in vitro leishmanicidal activity and cytotoxicity of pyrazole-containing macrocyclic polyamines 1-4 was assayed on Leishmania infantum and Leishmania braziliensis species. Compounds 1-4 were more active and less toxic than glucantime and both infection rates and ultrastructural alterations confirmed that 1 and 2 were highly leishmanicidal and induced extensive parasite cell damage. Modifications in the excretion products of parasites treated with 1-3 were also consistent with substantial cytoplasm alterations. Compound 2 was highlighted as a potent inhibitor of Fe-SOD in both species, whereas its effect on human CuZn-SOD was poor. Molecular modelling suggested that 2 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the enzyme`s antioxidant features.


Assuntos
Antiprotozoários/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Pirazóis/farmacologia , Superóxido Dismutase/efeitos dos fármacos , Animais , Antiprotozoários/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Leishmania braziliensis/enzimologia , Leishmania braziliensis/ultraestrutura , Leishmania infantum/enzimologia , Leishmania infantum/ultraestrutura , Leishmaniose/parasitologia , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Modelos Moleculares , Poliaminas/química , Poliaminas/farmacologia , Proteínas de Protozoários/efeitos dos fármacos , Proteínas de Protozoários/metabolismo , Pirazóis/química , Superóxido Dismutase/metabolismo
6.
Materials (Basel) ; 17(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38399029

RESUMO

Due to a continuously developing population, our consumption of one of the most widely used building materials, concrete, has increased. The production of concrete involves the use of cement whose production is one of the main sources of CO2 emissions; therefore, a challenge for today's society is to move towards a circular economy and develop building materials with a reduced environmental footprint. This study evaluates the possibility of using new sustainable supplementary cementitious materials (SCMs) from waste such as recycled concrete aggregates (RCAs) and mixed recycled aggregates (MRAs) from construction and demolition waste, as well as bottom ash from olive biomass (BBA-OL) and eucalyptus biomass ash (BBA-EU) derived from the production of electricity. A micronisation pre-treatment was carried out by mechanical methods to achieve a suitable fineness and increase the SCMs' specific surface area. Subsequently, an advanced characterisation of the new SCMs was carried out, and the acquired properties of the new cements manufactured with 25% cement substitution in the new SCMs were analysed in terms of pozzolanicity, mechanical behaviour, expansion and setting time tests. The results obtained demonstrate the feasibility of using these materials, which present a composition with potentially reactive hydraulic or pozzolanic elements, as well as the physical properties (fineness and grain size) that are ideal for SCMs. This implies the development of new eco-cements with suitable properties for possible use in the construction industry while reducing CO2 emissions and the industry's carbon footprint.

7.
J Frailty Aging ; 13(1): 10-20, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305438

RESUMO

BACKGROUND: We aimed to identify the association among nutritional status, Oral Health-Related Quality of Life (OHRQoL) and frailty, and to estimate the mediation effect of these conditions between age and frailty in a group of Mexico City nursing home residents. METHODS: We conducted a cross-sectional study. Fried's phenotype criteria, Full Mini Nutritional Assessment, and General Oral Health Assessment Index was applied. RESULTS: The participants (n = 286) mean age was 82.4 (± 9.2) years. The prevalence of frailty was 58%, and the prevalence of malnutrition and the risk of malnutrition were 22.7% and 59.5%, respectively. A higher risk of frailty was associated with older age (p = 0.015), sex (women) (p = 0.041), poor nutritional status (p <0.001) and compromised OHRQoL (p <0.001). Approximately 40% of the effect of age on frailty was mediated by nutritional status and OHRQoL (p <0.05). CONCLUSION: A strong association between nutritional status and frailty was observed. Additionally, OHRQoL was associated with frailty. The effect of age on frailty was mediated by OHRQoL and nutritional status. Interventions targeted to improve nutritional status and oral health may contribute to preventing or delaying the onset of frailty.


Assuntos
Fragilidade , Desnutrição , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Estado Nutricional , Fragilidade/epidemiologia , Fragilidade/complicações , Qualidade de Vida , Estudos Transversais , México/epidemiologia , Avaliação Geriátrica , Desnutrição/epidemiologia , Avaliação Nutricional , Casas de Saúde
8.
Eur Rev Med Pharmacol Sci ; 28(6): 2464-2482, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567607

RESUMO

OBJECTIVE: Vitiligo is a common systemic, idiopathic autoimmune disease. The aim of this study was to analyze the frequency of variants of the superoxide dismutase 1 (SOD1) gene (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) and circulating plasma protein levels through in-silico analysis. PATIENTS AND METHODS: Blood samples were collected from adult patients of both sexes with a clinical diagnosis of vitiligo. ELISA tests for SOD and analysis of gene variants by qPCR were compared to a disease-free reference group. RESULTS: The population analyzed was young people between 29 and 37 years old, with a higher percentage of women. The population was found in the Hardy-Weinberg equilibrium (HWE). The 50 bp Ins/Del, rs4817415, and rs2070424 variants showed no significant difference between groups (p > 0.05). Although, in the dominant model, the CT and CTTT genotypes of the rs1041740 and rs17880135 variants showed an association with susceptibility to vitiligo compared to the control. Plasma SOD levels showed significant differences between the groups, and when stratified according to the genotypes of each variant, there was a significant difference, except with the rs17880135 variant. The haplotypes InsCGTC and InsAGCC are shown to be risk factors for susceptibility to vitiligo. The in-silico analysis demonstrated that the rs4817415, rs2070424, rs1041740, and rs17880135 variants of the SOD1 gene participate in the modification of selected regulatory elements for differentiating the protein, transcription factors, and long non-coding RNA. CONCLUSIONS: Information regarding the pathogenesis of vitiligo helps recognize risk factors and identify the relationship of diagnostic markers of cell damage inherent to the disease. This will help improve aspects of prevention and the choice of treatment alternatives appropriate to each case.


Assuntos
Vitiligo , Masculino , Adulto , Humanos , Feminino , Adolescente , Superóxido Dismutase-1/genética , Vitiligo/genética , Genótipo , Fatores de Risco , Proteínas Sanguíneas/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único
9.
Qual Life Res ; 22(2): 295-308, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22367682

RESUMO

PURPOSE: Psychometric inadequacy interferes with the assessment of patient-reported health outcomes. This study examined the psychometric properties of several standardized measures in health research. METHODS: Participants completed health outcomes measures including the FACT-G, SF-36, MOS Social Support Survey, and CES-D. Psychometric properties examined include reliability, and construct and concurrent validity. RESULTS: 320 BCS including 88 African-, 95 English-proficient Latina-, and 137 Limited English-proficient Latina-Americans participated. The findings demonstrate acceptable reliability (α > 0.70) and consistent factor structures for most measures with the variance ranging from 56 to 84%. The FACT-G physical well-being and SF-36 role limitations subscales had the best fitting structures. Concurrent validity showed the FACT-G subscales correlated with their appropriate counterparts. CONCLUSIONS: Despite being commonly used instruments in HRQOL (e.g., FACT-G, SF-36) and QOL (e.g., CES-D, MOS) research, few studies reported the psychometric properties of these and when applied cross-culturally. However, evaluating the psychometric properties of measures in health outcomes research should be done routinely.


Assuntos
Neoplasias da Mama/psicologia , Avaliação de Resultados em Cuidados de Saúde , Psicometria/instrumentação , Qualidade de Vida , Inquéritos e Questionários , Sobreviventes/psicologia , Adulto , Idoso , California , Comparação Transcultural , Cultura , Etnicidade/psicologia , Etnicidade/estatística & dados numéricos , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Apoio Social , Fatores Socioeconômicos
10.
Biol Trace Elem Res ; 201(4): 1559-1566, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35486317

RESUMO

Sodium selenite modulates the activity of lymphocytes. It negatively regulates the suppressive activity of cells and increases the immune response. In this study, we evaluated whether the regulatory T cell differentiation was modulated by sodium selenite. The percentages of CD4+CD25+Foxp3+, CD4+CD25+, and CD4+CTLA-4+ cells in CD4+ T cells cultures stimulated with IL-2 and TGF-ß in the presence or absence of selenium, in the form of sodium selenite (2.0×10-6M), were evaluated by flow cytometry. The mRNA expression of TET2/3 enzymes and IL-10 was analyzed by RT-qPCR and the levels of IL-10 were measured by an ELISA. We observed a decrease in CD4+CD25+Foxp3+ and CD4+CTLA-4+ cells in presence of selenium. However, normal percentages were reached again after selenium removal. An increase in CD4+CTL4-4+ cells was detected in selenium-primed cell cultures in absence of IL-2 and TGF-ß. In addition, we observed a decrease in TET3 in presence of selenium. Finally, we observed an augment in IL-10 transcription and protein levels and relative expression of TET2 in cultures exposed to selenium. We suggest that selenium reversibly affects the regulatory T cell differentiation in vitro. Likewise, selenium may modulate Treg percentages promoting optimal immune responses and, at the same time, the expression of specific suppressor molecules.


Assuntos
Interleucina-10 , Selênio , Linfócitos T Reguladores/metabolismo , Selenito de Sódio/farmacologia , Selenito de Sódio/metabolismo , Antígeno CTLA-4/metabolismo , Selênio/farmacologia , Selênio/metabolismo , Interleucina-2/genética , Interleucina-2/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Diferenciação Celular , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/metabolismo
11.
Eur Rev Med Pharmacol Sci ; 27(7): 3088-3095, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37070912

RESUMO

OBJECTIVE: The aim of this investigation was to determine the frequency and association of the variants rs4817415, rs2070424, and rs1041740 of the SOD1 gene in healthy women and breast cancer (BC) patients. PATIENTS AND METHODS: Genomic DNA samples from 146 healthy women and 130 patients with BC were analyzed. RESULTS: GG genotype (OR 2.54, 95% CI 1.31-4.91, p = 0.0073) and the G allele (OR 1.37, 95% CI 1.09-1.73, p = 0.007) of the rs2070424 variant and CC genotype (OR 1.67, 95% CI 1.04-0.2.70, p = 0.0444) and allele C (OR 1.58, 95% CI 1.09-2.29, p = 0.0183) of the rs1041740 variant of SOD1 gene were associated as risk factors for BC susceptibility relative to the control group. Study groups comparison of the stratification by menopausal status showed an association of susceptibility to BC risk with carriers of the GG genotype (OR 2.9, 95% CI 1.11-7.81, p = 0.042) of the rs2070424 variant and with the premenopausal status of the study group and the TT (OR 2.89, 95% CI 1.73-4.85, p = 0.001) genotype of the rs1041740 variant. Furthermore, differences were observed in the patients with BC who were carriers of the CC genotype of the rs4817415 variant with elevated Ki-67 (≥ 20%) and who presented lymph node metastasis and stage III-IV BC (p<0.05). Two common haplotypes were identified in the study groups: CAC (protective factor), and CGC (risk factor) (p<0.05). CONCLUSIONS: The rs2070424 and rs1041740 variants of the SOD1 gene and the CGC haplotype were associated as risk susceptibility factors of BC in this sample analyzed.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Superóxido Dismutase-1/genética , Predisposição Genética para Doença , Genótipo , Fatores de Risco , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Frequência do Gene
12.
ESMO Open ; 7(1): 100360, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34973512

RESUMO

Since completion of the Trastuzumab for Gastric Cancer study, trastuzumab with doublet chemotherapy (a fluoropyrimidine and a platinum) has been the gold-standard first-line therapy for patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2-positive (HER2+) gastroesophageal adenocarcinoma (GEA). The safety and efficacy of 23 studies of first-line trastuzumab plus doublet chemotherapy, without checkpoint inhibitors (n = 19) or with checkpoint inhibitors (n = 4), conducted in patients with locally advanced unresectable or metastatic HER2+ GEA, including phase II/III, prospective, and retrospective observational studies, were summarized. In studies without checkpoint inhibitors, the median duration of trastuzumab treatment ranged from 19.5 to 39.0 weeks and from 15.3 to 30.0 weeks for chemotherapy. In studies with checkpoint inhibitors, the median duration of pembrolizumab/trastuzumab/chemotherapy was 30 weeks, and 18 weeks for chemotherapy. In studies without checkpoint inhibitors, treatment-emergent adverse events (TEAEs) of grade ≥3 ranged from 32% to 84%. Serious adverse events (SAEs) ranged from 15% to 39%. Adverse events resulting in discontinuation ranged from 0% to 30%. Treatment-related deaths occurred in 0%-9% of patients. In studies with checkpoint inhibitors, TEAEs of grade ≥3 were 57%. SAEs ranged from 31% to 38%. Adverse events resulting in discontinuation ranged from 5% to 24%. Treatment-related deaths occurred in 0%-3% of patients. In studies without checkpoint inhibitors, objective response rate (ORR) ranged from 39% to 82%, median progression-free survival (PFS) from 5.7 to 11.6 months, and median overall survival (OS) from 11.2 to 27.6 months. In studies with checkpoint inhibitors, ORR ranged from 39% to 86%, median PFS from 8.0 to 13.0 months, and median OS from 19.3 to 27.3 months. This review provides a historical benchmark on safety and efficacy of available first-line chemotherapy-based standard of care for patients with locally advanced unresectable or metastatic HER2+ GEA.


Assuntos
Adenocarcinoma , Receptor ErbB-2 , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/uso terapêutico , Estudos Retrospectivos , Trastuzumab/efeitos adversos
13.
ESMO Open ; 7(5): 100563, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36029651

RESUMO

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric and gastroesophageal adenocarcinoma (GEA) is globally treated with chemotherapy plus trastuzumab. Novel therapeutic strategies strive to not only optimize efficacy, but also limit toxicities. In MAHOGANY cohort A, margetuximab, an Fc-engineered, anti-HER2 monoclonal antibody (mAb) was combined with retifanlimab, an anti-programmed cell death protein 1 mAb, in the first-line HER2-positive/programmed death-ligand 1 (PD-L1)-positive GEA. PATIENTS AND METHODS: MAHOGANY cohort A part 1 is a single-arm trial to evaluate margetuximab plus retifanlimab in patients with HER2 immunohistochemistry 3+, PD-L1-positive (combined positive score ≥1%), and non-microsatellite instability-high tumors. Primary objectives for cohort A were safety/tolerability and the confirmed objective response rate (ORR). RESULTS: As of 3 August 2021, 43 patients were enrolled and received margetuximab/retifanlimab. Nine grade 3 treatment-related adverse events (TRAEs) were reported in eight (18.6%) patients and eight serious TRAEs in seven (16.3%) patients. There were no grade 4/5 TRAEs. Three patients discontinued margetuximab/retifanlimab because of immune-related adverse events. The ORR by independent assessment was 53% [21/40 (95% confidence interval (CI) 36.1-68.5)], with a median duration of response of 10.3 months (95% CI 4.6-not evaluable); disease control rate was 73% [29/40 (95% CI 56.1-85.4)]. The study sponsor discontinued the study in advance of the planned enrollment when it became apparent that the study design would no longer meet the requirements for drug approval because of recent advances in the treatment of GEA. CONCLUSIONS: The chemotherapy-free regimen of combined margetuximab/retifanlimab as first-line treatment in double biomarker-selected patients demonstrated a favorable toxicity profile compared with historical outcomes using chemotherapy plus trastuzumab. The ORR observed in this study compares favorably versus ORR observed with other chemotherapy-free approaches.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Antígeno B7-H1/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Inibidores de Checkpoint Imunológico
14.
Artigo em Inglês | MEDLINE | ID: mdl-21905499

RESUMO

BACKGROUND: Second-generation oral antihistamines (AH) and intranasal corticosteroids (ICS) are the most widely used drugs for allergic rhinitis (AR). OBJECTIVE: To obtain information on the preferences for and applications of these drugs under conditions of routine clinical practice. METHODS: We performed a multicenter multidisciplinary observational study. Participating physicians completed a questionnaire with information on preferences for and application of drugs for AR, patient characteristics, and physician/patient satisfaction with the treatment provided (visual analog scale). RESULTS: A total of 1008 physicians participated in the study (primary care physicians, 53%; ear, nose, and throat specialists, 28%; allergologists, 19%). Treatment preferences in AR were AH combined with ICS (7.68), AH (7.25), and ICS (6.94). AH and ICS were used continuously by 58% and 71% of patients, respectively. Physicians reported having a good knowledge of the Allergic Rhinitis and its Impact on Asthma guidelines (93%), and 90% claimed to follow the guidelines. A total of 4040 patients were recruited (52% females, mean [SD] age 34 [14] years). The findings for AR were as follows: mean (SD) duration, 9 (8) years; persistent AR, 52%; mild AR, 72%; moderate AR, 7%; and severe AR, 1%. Patients considered the disorder to be well controlled/almost controlled (79%). As for treatment, 77% followed the regimen recommended by the physician. Oral treatment (41%) and intranasal treatment (22%) were preferred, while 35% showed no preference for any given administration route. The treatments prescribed were AH combined with ICS (66%), AH (20%), ICS (11%), other antihistamines (4%), and other drugs (6%). Combination treatment was the preferred therapy, regardless of the type of rhinitis. CONCLUSIONS: Physicians prefer and more often use combination treatment with oral AH and ICS, regardless of the frequency and intensity of AR.


Assuntos
Alérgenos/imunologia , Pólen/imunologia , Padrões de Prática Médica/estatística & dados numéricos , Prescrições/estatística & dados numéricos , Rinite Alérgica Sazonal/epidemiologia , Corticosteroides/uso terapêutico , Adulto , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Preferência do Paciente , Satisfação do Paciente , Poaceae , Guias de Prática Clínica como Assunto , Rinite Alérgica Sazonal/tratamento farmacológico , Espanha , Inquéritos e Questionários
15.
Environ Technol ; 42(8): 1165-1178, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31475614

RESUMO

World's energy consumption has doubled in the last four decades, this demand has been covered by the usage of fossil fuels; which are an important source of greenhouse gases emissions, entailing climate change. An efficient less polluting management alternative is the anaerobic digestion (AD) process which generates biogas derived from organic matter. The methane contained at the biogas is considered a biofuel that can generate electricity and heat through its combustion. Biochemical Methane Potential (BMP) essays are standardized methodologies carried out to estimate the energy potential of an organic residue. After performing a BMP test for 13 residual biomass samples, it can be concluded that fresh livestock rumen and manure were the best substrates to generate higher biogas yields; ranging from 1119-1669 ml/g VSadded, with high methane content (65%

Assuntos
Biocombustíveis , Metano , Anaerobiose , Animais , Biomassa , Esterco , Suínos
17.
Clin Exp Med ; 20(4): 615-626, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32506205

RESUMO

B cell-activating factor (BAFF) is an essential cytokine in primary Sjögren's syndrome (pSS) physiopathology. It has been reported that pSS patients develop germinal center-like (GC-like) structures in their minor salivary glands (MSGs). BAFF, BAFF-R, TACI, and BCMA expression was analyzed in MSGs from 29 subjects (nonspecific chronic sialadenitis and focal lymphocytic sialadenitis with the presence [pSS-GC(+)] or absence [pSS-GC(-)] of GC-like structures). Twenty-four percent of patients showed ectopic GC-like structures and a high focus score [p < 0.001 vs pSS-GC(-)]. BAFF serum levels (sBAFF) were high in pSS patients (p = 0.025 vs healthy subjects). However, the pSS-GC(-) group showed higher sBAFF levels than pSS-GC(+) patients. BAFF and BAFF-R glandular expression levels were higher in pSS-GC(+) patients, without significant differences compared to pSS-GC(-) patients. Soluble levels of BAFF correlated with anti-La/SSB antibodies and disease duration. Our results showed that BAFF could contribute to focal lymphocytic infiltration. The role of BAFF-binding receptors in MSGs is proposed as a mechanism for the possible establishment of ectopic GC-like structures and disease progression in some patients. In conclusion, this study supports previous evidence that considers the active BAFF system role in the pathogenesis of pSS and the need for strong biomarkers in this disease.


Assuntos
Fator Ativador de Células B/metabolismo , Receptor do Fator Ativador de Células B/metabolismo , Glândulas Salivares Menores/patologia , Síndrome de Sjogren/metabolismo , Adulto , Idoso , Fator Ativador de Células B/sangue , Antígeno de Maturação de Linfócitos B/metabolismo , Estudos de Casos e Controles , Feminino , Centro Germinativo/patologia , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Glândulas Salivares Menores/fisiologia , Índice de Gravidade de Doença , Síndrome de Sjogren/etiologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo
18.
Plant Biol (Stuttg) ; 11(5): 671-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19689774

RESUMO

Boron (B) toxicity has become important in areas close to the Mediterranean Sea where intensive agriculture has been developed. The objective of this research was to study the effects of B toxicity (0.5 mM and 2.0 mM B) on nitrogen (N) assimilation of two tomato cultivars that are often used in these areas. Leaf biomass, relative leaf growth rate (RGR(L)), concentration of B, nitrate (NO(3) (-)), ammonium (NH(4) (+)), organic N, amino acids and soluble proteins, as well as nitrate reductase (NR), nitrite reductase (NiR), glutamine synthase (GS), glutamate synthetase (GOGAT) and glutamate dehydrogenase (GDH) activities were analysed in leaves. Boron toxicity significantly decreased leaf biomass, RGR(L), organic N, soluble proteins, and NR and NiR activities. The lowest NO(3) (-) and NH(4) (+) concentration in leaves was recorded when plants were supplied with 2.0 mM B in the root medium. Total B, amino acids, activities of GS, GOGAT and GDH increased under B toxicity. Data from the present study prove that B toxicity causes inhibition of NO(3) (-) reduction and increases NH(4) (+) assimilation in tomato plants.


Assuntos
Boro/toxicidade , Nitratos/metabolismo , Nitrogênio/metabolismo , Compostos de Amônio Quaternário/metabolismo , Compostos de Amônio Quaternário/farmacologia , Solanum lycopersicum/metabolismo , Glutamato Desidrogenase/metabolismo , Glutamato Sintase (NADH)/metabolismo , Glutamato-Amônia Ligase/metabolismo , Região do Mediterrâneo
19.
Plant Sci ; 176(4): 545-52, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26493145

RESUMO

To gain an insight into the role of lignification and membrane permeability in the root response to boron (B) toxicity, lignification-related enzymes and a number of physiological and oxidative stress parameters were analyzed in two tomato (Solanum lycopersicum L.) cultivars (Kosaco and Josefina) subjected to 0.05 (control), 0.5 and 2mM B during 16 days. 2mM B supply inhibited root growth and increased the root B concentration in both tomato cultivars. Although excess B increased the hydrogen peroxide (H2O2) concentration in Kosaco, no major changes were observed in other oxidative-stress-related parameters. High levels of B supply also induced higher lignin deposition in Kosaco roots but did not in Josefina ones. The latter result was associated with an increase of the polyphenol oxidase (PPO), guaiacol peroxidase (GPOX) and soluble syringaldazine peroxidase (SPOX) activity in Kosaco roots. Boron toxicity did not induce lipid peroxidation but increased the leakage of K(+) and the passive efflux of B in tomato roots. We conclude that high concentrations of B do not cause major oxidative or membrane damage in tomato roots. The data also indicate that high levels of B supply induce a higher lignin deposition in Kosaco roots but not in Josefina ones. This phenomenon suggests that lignification is not an essential factor reducing root growth in tomato plants, however, it proves that exist a high genotypic variation in response to excess B at root level.

20.
Plant Physiol Biochem ; 135: 77-86, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30513478

RESUMO

Transgenic tomato plants (Solanum lycopersicum L. cv. MicroTom) overexpressing both the K+,Na+/H+ antiporter LeNHX2 and the regulatory kinase SlSOS2 were produced by crossing transgenic homozygous lines overexpressing LeNHX2 and SlSOS2. LeNHX2 expression was enhanced in plants overexpressing LeNHX2 but surprisingly even more in plants overexpressing SlSOS2 with and without LeNHX2. All transgenic plants showed better NaCl tolerance than wild type controls and plants overexpressing both LeNHX2 and SlSOS2 grew better under saline conditions than plants overexpressing only one of these genes. Yield related parameters indicated that single and above all double transgenic plants performed significantly better than wild type controls. All transgenic plants produced fruits with a higher K+ content than wild-type plants and plants overexpressing SlSOS2 accumulated more Na+ in fruits than the rest of the plants when grown with NaCl. Roots, stems and leaves of transgenic plants overexpressing LeNHX2 showed a higher K+ content than wild type and single transgenic plants overexpressing SlSOS2. Na+ content in stems and leaves of NaCl treated plants was higher in SlSOS2 overexpressing plants than in wild type and LeNHX2 single transgenic plants. All transgenic lines showed a higher leaf relative water content and a higher plant water content and water use efficiency than wild type controls when both were grown in the presence of NaCl. Results in this work indicate that the joint overexpression of LeNHX2 and SlSOS2 improves growth and water status under NaCl stress, affects K+ and Na+ homeostasis and enhances fruit yield of tomato plants.


Assuntos
Antiporters/fisiologia , Frutas/crescimento & desenvolvimento , Genes de Plantas/fisiologia , Proteínas de Plantas/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Solanum lycopersicum/fisiologia , Antiporters/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Solanum lycopersicum/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Caules de Planta/metabolismo , Plantas Geneticamente Modificadas , Potássio/metabolismo , Proteínas Serina-Treonina Quinases/genética , Tolerância ao Sal , Plantas Tolerantes a Sal , Sódio/metabolismo , Água/metabolismo
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