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1.
Gut ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38754953

RESUMO

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies. DESIGN: We used the KPC mouse model (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) and primary tumour cell lines to investigate putative CSC populations. Transcriptomic analyses were conducted to pinpoint new genes involved in immune evasion. Overexpressing and knockout cell lines were established with lentiviral vectors. Subsequent in vitro coculture assays, in vivo mouse and zebrafish tumorigenesis studies, and in silico database approaches were performed. RESULTS: Using the KPC mouse model, we functionally confirmed a population of cells marked by EpCAM, Sca-1 and CD133 as authentic CSCs and investigated their transcriptional profile. Immune evasion signatures/genes, notably the gene peptidoglycan recognition protein 1 (PGLYRP1), were significantly overexpressed in these CSCs. Modulating PGLYRP1 impacted CSC immune evasion, affecting their resistance to macrophage-mediated and T-cell-mediated killing and their tumourigenesis in immunocompetent mice. Mechanistically, tumour necrosis factor alpha (TNFα)-regulated PGLYRP1 expression interferes with the immune tumour microenvironment (TME) landscape, promoting myeloid cell-derived immunosuppression and activated T-cell death. Importantly, these findings were not only replicated in human models, but clinically, secreted PGLYRP1 levels were significantly elevated in patients with PDAC. CONCLUSIONS: This study establishes PGLYRP1 as a novel CSC-associated marker crucial for immune evasion, particularly against macrophage phagocytosis and T-cell killing, presenting it as a promising target for PDAC immunotherapy.

2.
Biomolecules ; 13(11)2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-38002329

RESUMO

BACKGROUND: Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. METHODS: Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. RESULTS: The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. CONCLUSIONS: These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner.


Assuntos
Nanopartículas , Neoplasias da Glândula Tireoide , Humanos , Animais , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Cetuximab , Ácido Láctico , Ácido Poliglicólico , Glicóis , Distribuição Tecidual , Radioisótopos do Iodo , Qualidade de Vida , Linhagem Celular Tumoral , Neoplasias da Glândula Tireoide/tratamento farmacológico , Receptores ErbB , Portadores de Fármacos
3.
J Environ Manage ; 341: 118092, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37167698

RESUMO

The sustainability of Mediterranean croplands is threatened by climate warming and rainfall reduction. The use of biochar as an amendment represents a tool to store organic carbon (C) in soil. The vulnerability of soil organic C (SOC) to the joint effects of climate change and biochar application needs to be better understood by investigating its main pools. Here, we evaluated the effects of partial rain exclusion (∼30%) and temperature increase (∼2 °C), combined with biochar amendment, on the distribution of soil organic matter (SOM) into particulate organic matter (POM) and the mineral-associated organic matter (MAOM). A set of indices suggested an increase in thermal stability in response to biochar addition in both POM and MAOM fractions. The MAOM fraction, compared to the POM, was particularly enriched in labile substances. Data from micro-Raman spectroscopy suggested that the POM fraction contained biochar particles with a more ordered structure, whereas the structural order decreased in the MAOM fraction, especially after climate manipulation. Crystalline Fe oxides (hematite) and a mix of ferrihydrite and hematite were detected in the POM and in the MAOM fraction, respectively, of the unamended plots under climate manipulation, but not under ambient conditions. Conversely, in the amended soil, climate manipulation did not induce changes in Fe speciation. Our work underlines the importance of discretely taking into account responses of both MAOM and POM to better understand the mechanistic drivers of SOC storage and dynamics.


Assuntos
Mudança Climática , Solo , Solo/química , Carvão Vegetal , Carbono , Material Particulado
4.
Gut ; 72(2): 345-359, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35428659

RESUMO

OBJECTIVE: The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models. DESIGN: Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies, K-Ras +/LSL-G12D;Trp53 LSL-R172H;Pdx1-Cre mice (KPC) and the K-Ras +/LSL-G12D;Pdx1-Cre mice (KC) were crossed with Loxl2 allele floxed mice (Loxl2Exon2 fl/fl) or conditional Loxl2 overexpressing mice (R26Loxl2 KI/KI) to generate KPCL2KO or KCL2KO and KPCL2KI or KCL2KI mice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation. RESULTS: Using these PDAC mouse models, we show that while Loxl2 ablation had little effect on primary tumour development and growth, its loss significantly decreased metastasis and increased overall survival. We attribute this effect to non-cell autonomous factors, primarily ECM remodelling. Loxl2 overexpression, on the other hand, promoted primary and metastatic tumour growth and decreased overall survival, which could be linked to increased EMT and stemness. We also identified tumour-associated macrophage-secreted oncostatin M (OSM) as an inducer of LOXL2 expression, and show that targeting macrophages in vivo affects Osm and Loxl2 expression and collagen fibre alignment. CONCLUSION: Taken together, our findings establish novel pathophysiological roles and functions for LOXL2 in PDAC, which could be potentially exploited to treat metastatic disease.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Transição Epitelial-Mesenquimal/genética , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Modelos Animais de Doenças , Macrófagos/metabolismo , Aminoácido Oxirredutases/genética , Neoplasias Pancreáticas
5.
Cancers (Basel) ; 13(3)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530455

RESUMO

Cancer stem cells (CSCs) are defined as a subpopulation of "stem"-like cells within the tumor with unique characteristics that allow them to maintain tumor growth, escape standard anti-tumor therapies and drive subsequent repopulation of the tumor. This is the result of their intrinsic "stem"-like features and the strong driving influence of the CSC niche, a subcompartment within the tumor microenvironment that includes a diverse group of cells focused on maintaining and supporting the CSC. CXCL12 is a chemokine that plays a crucial role in hematopoietic stem cell support and has been extensively reported to be involved in several cancer-related processes. In this review, we will provide the latest evidence about the interactions between CSC niche-derived CXCL12 and its receptors-CXCR4 and CXCR7-present on CSC populations across different tumor entities. The interactions facilitated by CXCL12/CXCR4/CXCR7 axes seem to be strongly linked to CSC "stem"-like features, tumor progression, and metastasis promotion. Altogether, this suggests a role for CXCL12 and its receptors in the maintenance of CSCs and the components of their niche. Moreover, we will also provide an update of the therapeutic options being currently tested to disrupt the CXCL12 axes in order to target, directly or indirectly, the CSC subpopulation.

6.
Int J Mol Sci ; 21(23)2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33287468

RESUMO

The authors recently reported on the potential of targeting SRC kinase signaling in pancreatic cancer stem cells [...].

7.
Int J Mol Sci ; 21(20)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050159

RESUMO

The proto-oncogene nonreceptor tyrosine-protein kinase SRC is a member of the SRC family of tyrosine kinases (SFKs), and its activation and overexpression have been shown to play a protumorigenic role in multiple solid cancers, including pancreatic ductal adenocarcinoma (PDAC). PDAC is currently the seventh-leading cause of cancer-related death worldwide, and, by 2030, it is predicted to become the second-leading cause of cancer-related death in the United States. PDAC is characterized by its high lethality (5-year survival of rate of <10%), invasiveness, and chemoresistance, all of which have been shown to be due to the presence of pancreatic cancer stem cells (PaCSCs) within the tumor. Due to the demonstrated overexpression of SRC in PDAC, we set out to determine if SRC kinases are important for PaCSC biology using pharmacological inhibitors of SRC kinases (dasatinib or PP2). Treatment of primary PDAC cultures established from patient-derived xenografts with dasatinib or PP2 reduced the clonogenic, self-renewal, and tumor-initiating capacity of PaCSCs, which we attribute to the downregulation of key signaling factors such as p-FAK, p-ERK1-2, and p-AKT. Therefore, this study not only validates that SRC kinases are relevant and biologically important for PaCSCs but also suggests that inhibitors of SRC kinases may represent a possible future treatment option for PDAC patients, although further studies are still needed.

8.
Theranostics ; 10(7): 3263-3280, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194867

RESUMO

Background: The LRP1 (CR9) domain and, in particular, the sequence Gly1127-Cys1140 (P3) plays a critical role in the binding and internalization of aggregated LDL (agLDL). We aimed to evaluate whether immunization with P3 reduces high-fat diet (HFD)-induced atherosclerosis. Methods: Female New Zealand White (NZW) rabbits were immunized with a primary injection and four reminder doses (R1-R4) of IrP (irrelevant peptide) or P3 conjugated to the carrier. IrP and P3-immunized rabbits were randomly divided into a normal diet group and a HFD-fed group. Anti-P3 antibody levels were determined by ELISA. Lipoprotein profile, circulating and tissue lipids, and vascular pro-inflammatory mediators were determined using standardized methods while atherosclerosis was determined by confocal microscopy studies and non-invasive imaging (PET/CT and Doppler ultrasonography). Studies treating human macrophages (hMΦ) and coronary vascular smooth muscle cells (hcVSMC) with rabbit serums were performed to ascertain the potential impact of anti-P3 Abs on the functionality of these crucial cells. Results: P3 immunization specifically induced the production of anti-P3 antibodies (Abs) and did not alter the lipoprotein profile. HFD strongly induced cholesteryl ester (CE) accumulation in the aorta of both the control and IrP groups, and their serum dose-dependently raised the intracellular CE of hMΦ and hcVSMC, promoting TNFR1 and phospho-NF-kB (p65) overexpression. These HFD pro-inflammatory effects were dramatically decreased in the aorta of P3-immunized rabbits and in hMΦ and hcVSMC exposed to the P3 rabbit serums. Microscopy studies revealed that P3 immunization reduced the percentage of lipids, macrophages, and SMCs in the arterial intima, as well as the atherosclerotic extent and lesion area in the aorta. PET/CT and Doppler ultrasonography studies showed that the average standardized uptake value (SUVmean) of the aorta and the arterial resistance index (ARI) of the carotids were more upregulated by HFD in the control and IrP groups than the P3 group. Conclusions: P3 immunization counteracts HFD-induced fatty streak formation in rabbits. The specific blockade of the LRP1 (CR9) domain with Anti-P3 Abs dramatically reduces HFD-induced intracellular CE loading and harmful coupling to pro-inflammatory signaling in the vasculature.


Assuntos
Aterosclerose/prevenção & controle , Imunização , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/imunologia , Fragmentos de Peptídeos/imunologia , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Aorta/citologia , Aorta/diagnóstico por imagem , Aterosclerose/sangue , Aterosclerose/diagnóstico por imagem , Aterosclerose/imunologia , Células Cultivadas , Ésteres do Colesterol/metabolismo , Vasos Coronários/citologia , Dieta Hiperlipídica , Feminino , Humanos , Lipídeos/sangue , Lipoproteínas/sangue , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/química , Macrófagos/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Domínios Proteicos , Coelhos , Distribuição Aleatória , Ultrassonografia Doppler , Resistência Vascular
9.
Cancers (Basel) ; 12(3)2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32183251

RESUMO

The recognition of intra-tumoral cellular heterogeneity has given way to the concept of the cancer stem cell (CSC). According to this concept, CSCs are able to self-renew and differentiate into all of the cancer cell lineages present within the tumor, placing the CSC at the top of a hierarchical tree. The observation that these cells-in contrast to bulk tumor cells-are able to exclusively initiate new tumors, initiate metastatic spread and resist chemotherapy implies that CSCs are solely responsible for tumor recurrence and should be therapeutically targeted. Toward this end, dissecting and understanding the biology of CSCs should translate into new clinical therapeutic approaches. In this article, we review the CSC concept in cancer, with a special focus on hepatocellular carcinoma.

10.
Environ Monit Assess ; 188(2): 102, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26787271

RESUMO

Water shortage and soil qualitative degradation are significant environmental problems in arid and semi-arid regions of the world. The increasing demand for water in agriculture and industry has resulted in the emergence of wastewater use as an alternative in these areas. Textile wastewater is produced in surplus amounts which poses threat to the environment as well as associated flora and fauna. A 60-day incubation study was performed to assess the effects of untreated textile wastewater at 0, 25, 50, 75, and 100% dilution levels on the physico-chemical and some microbial and enzymatic properties of an aridisol soil. The addition of textile wastewater provoked a significant change in soil pH and electrical conductivity and soil dehydrogenase and urease activities compared to the distilled-water treated control soil. Moreover, compared to the control treatment, soil phosphomonoesterase activity was significantly increased from 25 to 75% application rates, but decreased at 100% textile wastewater application rate. Total and available soil N contents increased significantly in response to application of textile wastewater. Despite significant increases in the soil total P contents after the addition of textile wastewater, soil available P content decreased with increasing concentration of wastewater. Changes in soil nutrient contents and related enzymatic activities suggested a dynamic match between substrate availability and soil N and P contents. Aridisols have high fixation and low P availability, application of textile wastewater to such soils should be considered only after careful assessment.


Assuntos
Irrigação Agrícola/métodos , Monitoramento Ambiental , Microbiologia do Solo , Solo/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Resíduos Industriais , Nitrogênio/análise , Fósforo/análise , Poluentes do Solo/análise , Indústria Têxtil , Têxteis
11.
Rev. Soc. Colomb. Oftalmol ; 49(2): 119-125, 2016. ilus. tab. graf.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-906996

RESUMO

Diseño: Estudio descriptivo y trasversal. Objetivos: Medición del grosor coroideomacular en el ojo contralateral (ojo sano) de pacientes con coriorretinopatía serosa central (CSC), utilizando tomografía óptica coherente de imagen de profundidad mejorada (EDI OCT). Pacientes y métodos: Fueron evaluados 32 ojos de 16 pacientes voluntarios, con diagnostico de coriorretinopatía serosa central (CSC) aguda. Ambos ojos fueron sometidos a estudio de tomografía óptica de dominio espectral con profundidad mejorada (EDI SD-OCT) con el Tomógrafo RTVue® (Optovue, USA). Se realizó escaneo horizontal de alta definición a través de la fóvea, tanto en el ojo afectado, como en el sano contralateral. Se realizaron 5 medidas del grosor coroideo. El promedio del grosor coroideo fue calculado y comparado, entre los ojos con CSC y el ojo contralateral. Resultados: El promedio de edad fue de 40+/-7 (rango entre 29 y 56 años). Quince de los 16 ojos sintomáticos eran derechos. Dos mujeres y 14 hombres. La media del grosor coroideo en el ojo sintomático fue de 470.4+/-35.7µm, y en el ojo contralateral el grosor fue de 413.4+/-47.1µm. La relación entre ambos ojos mostró una alta correlación (0,979) y una correlación estadísticamente significativa (p<0.001). Conclusión: La tomografía óptica coherente de dominio espectral con profundidad mejorada, es una herramienta útil en evaluar el grosor coroideo en pacientes con CSC, donde el grosor coroideo también aparece aumentado en el ojo contralateral.


Design: Descriptive and cross-sectional study. Objective: To measure macular choroidal thickness in fellow eyes of patients with central serous chorioretinopathy, using enhanced depth imaging optical coherence tomography (EDI OCT). Patients and methods: This is a descriptive, cross-sectional study. A total of 32 eyes of 16 patients were evaluated. Sixteen volunteers with acute central serous corioretinopathy (CSC) diagnosis underwent high-definition scanning using SD-OCT (RTVue®, Optovue, USA) with enhanced depth imaging technique (EDI OCT) in both eyes. One horizontal scan across the fovea was selected for each affected and healthy eye, five choroidal thickness measurements were taken. The average choroidal thickness was also calculated and compared among eyes with CSC and fellow eyes. Results: Mean age was 40+/-7 years (range between 29 and 56 years old). Fifteen of 16 symptomatic eyes where right eyes. Two women and 14 men were involved. The mean choroidal thickness in symptomatic eyes was 470.4+/-35.7 µm, and the fellow eyes thickness was 413.4+/-47.1 µm. The matching shows a high correlation (0,979) between paired samples and statistical signifi cance of its correlation (p<0.001). Conclusions: Enhanced depth imaging spectral-domain optical coherence tomography is a helpful tool for assessing choroidal thickness in fellow eyes of patients with CSC, where the choroid is as thickened as in affected eyes.


Assuntos
Coriorretinopatia Serosa Central , Técnicas de Diagnóstico Oftalmológico , Tomografia de Coerência Óptica
12.
J Mol Neurosci ; 57(3): 404-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26156202

RESUMO

Evidence is emerging that inflammation plays a key role in the pathophysiology of ischemic stroke (IS). The aim of this study was to explore, for the first time, the relationship between IL-1ß -31 T/C polymorphism and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). One hundred ninety-six patients with IS (117 diabetics and 79 nondiabetics) and 192 controls were recruited to enroll in this study. IL-1ß genotyping was performed by PCR-RFLP technique. After adjusting for sex, age, smoking, obesity, dyslipidemia, and hypertension, there was no significant difference in the distribution of IL-1ß -31 T/C genotypes and allele frequencies between IS patients with or without type 2 diabetes mellitus and control group (p > 0.05). Moreover, a significant positive correlation between serum IL-1ß level and glucose (p1 = 0.044) was showed. In addition, serum levels of IL-1ß were found to be higher among TT genotype carriers than TC and CC genotype carriers in ischemic stroke patients with or without T2DM but these differences were not significant. These results indicate that IL-1ß gene polymorphism might not be a risk factor in the development of ischemic stroke in Tunisian population.


Assuntos
Isquemia Encefálica/genética , Diabetes Mellitus Tipo 2/genética , Interleucina-1beta/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Glicemia/análise , Pressão Sanguínea , Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Comorbidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Inflamação , Interleucina-1beta/sangue , Lipídeos/sangue , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/epidemiologia , Tunísia/epidemiologia
13.
Microb Ecol ; 69(4): 798-812, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25724140

RESUMO

Ecological transformations derived from habitat fragmentation have led to increased threats to above-ground biodiversity. However, the impacts of forest fragmentation on soils and their microbial communities are not well understood. We examined the effects of contrasting fragment sizes on the structure and functioning of soil microbial communities from holm oak forest patches in two bioclimatically different regions of Spain. We used a microcosm approach to simulate the annual summer drought cycle and first autumn rainfall (rewetting), evaluating the functional response of a plant-soil-microbial system. Forest fragment size had a significant effect on physicochemical characteristics and microbial functioning of soils, although the diversity and structure of microbial communities were not affected. The response of our plant-soil-microbial systems to drought was strongly modulated by the bioclimatic conditions and the fragment size from where the soils were obtained. Decreasing fragment size modulated the effects of drought by improving local environmental conditions with higher water and nutrient availability. However, this modulation was stronger for plant-soil-microbial systems built with soils from the northern region (colder and wetter) than for those built with soils from the southern region (warmer and drier) suggesting that the responsiveness of the soil-plant-microbial system to habitat fragmentation was strongly dependent on both the physicochemical characteristics of soils and the historical adaptation of soil microbial communities to specific bioclimatic conditions. This interaction challenges our understanding of future global change scenarios in Mediterranean ecosystems involving drier conditions and increased frequency of forest fragmentation.


Assuntos
Florestas , Quercus/microbiologia , Quercus/fisiologia , Microbiologia do Solo , Secas , Solo/química , Espanha
14.
Bioprocess Biosyst Eng ; 38(6): 1127-41, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25601570

RESUMO

This work studies the sequential execution of dilute sulfuric acid (DAP) (0.1-0.75 %, v/v) and dilute sodium hydroxide (AKP) (0.25-3 %, w/v) [i.e., DAP followed by AKP (DAP+AKP) and vice versa (AKP+DAP)] at low temperatures (<121 °C) and short reaction times (5-60 min) for maximizing sugar recovery in the enzymatic hydrolysis of wheat straw with low enzyme dosage. The pretreatment effectiveness was measured by the sum of the severity factors of both pretreatments and the saccharification yield achieved in the subsequent stage of enzymatic hydrolysis. Degradation compounds were quantified and mass balance calculations were carried out for each pretreatment sequence to verify the correct account of the input biomass and output products. Results show that sequential pretreatments (AKP+DAP and DAP+AKP) had a positive effect in enzyme accessibility thus improving monosaccharide yields compared to single DAP and AKP pretreatments. DAP+AKP achieved a high xylose yield (ca. 0.867 of theoretical) at the DAP stage, while no xylose monosaccharides were detected in the subsequent AKP. After enzyme saccharification of double-pretreated solids, the total monosaccharide yield was 0.786 (of theoretical). For AKP+DAP sequence, lower results were obtained (total monosaccharide yield 0.783 of theoretical). Sequential pretreatments total yields increased by 21 % compared to single pretreatments. AKP removed more than half of the lignin from the wheat straw in all cases. Acid and alkali concentrations played a relevant role in all pretreatment sequences, while reaction time and temperature were less important with an almost-linear effect on the total monosaccharide yields.


Assuntos
Enzimas/metabolismo , Triticum/metabolismo , Biomassa , Hidrólise
15.
Rev. Soc. Colomb. Oftalmol ; 47(1): 62-71, 2014. ilus. tab.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-969272

RESUMO

Objetivo: evaluar objetivamente mediante el uso de angiografía de segmento anterior la reducción del grado de neovascularización corneal con la aplicación de bevacizumab subconjuntival. Diseño: serie de casos con intervención. Metodología: nueve ojos con neovascularización corneal estromal secundaria a diferentes condiciones se sometieron a la realización de angiografía fluoresceínica de segmento anterior; cuatro semanas después se aplicaron 3 dosis de bevacizumab subconjuntival limbar de 2,5 mg/0,1cc cada una sobre el cuadrante comprometido con un intervalo de un mes entre cada aplicación. Cuatro semanas después se realizó una nueva angiografía. Las fotos pre-aplicación y post aplicación fueron analizadas por 3 evaluadores. Se definió como mejoría si había una mejoría ≥30%, basado en una escala de mejoría de 0 a 10. Resultados: se encontró un alto rango de variabilidad en la regresión de la neovascularización corneal (entre 3% y 92%) con un promedio de mejoría del 41% y posibilidad de falla de 44,4% independientemente de su etiología. Se obtuvieron pobres resultados en presencia de cuerpos extraños en córnea (segmentos intraestromales o suturas corneales) con una mejoría entre 3% y 7%. Pacientes sin cuerpo extraño en córnea obtuvieron una mejoría promedio de la neovascuarización corneal del 70%. No hubo efectos secundarios sistémicos o locales. Conclusion: el uso del bevacizumab subconjuntival como terapia antiangiogénica es una alternativa con buena tasa de efectividad en pacientes con neovascularización corneal sin presencia de cuerpos extraños corneales.


Purpose: to assess corneal stromal neovascularization accurately and its improvement by using anterior segment fluorescein angiography imaging after subconjunctival bevacizumab injection. Design: interventional case series. Methodology: an anterior segment fluorescein angiography was performed in nine eyes with stromal neovascularization secondary to different etiologies. Patients underwent subconjunctival bevacizumab injections, each one receiving three injections containing 2,5mg/0,1ml bevacizumab each, at monthly intervals. Four weeks after the last injection was applied, a new anterior segment fluorescein angiography was done; pre and post-treatment angiographies were analyzed by three ophthalmologists. A favorable outcome was defined as an improvement of 30% in corneal neovascularization based on a previously established score from 0 to 10. Results: findings were variable, with corneal neovascularization improving between 3% and 92% (mean improvement 41%) for all eyes included, and a 44,4% chance of failure. Poor results were obtained from eyes that had some type of intracorneal foreign body such as intracorneal ring segments (ICRS) and corneal sutures with an improvement range from 3% to 7% whereas eyes with no foreign bodies had a mean reduction in corneal neovascularization of 70%. No side effects were reported. Conclusions: subconjunctival Bevacizumab use as antiangiogenic therapy is an alternative with a high success rate in patients without intracorneal foreign bodies, although it is clearly not as effective in patients with foreing body-induced neovascularization.


Assuntos
Neovascularização da Córnea/tratamento farmacológico , Angiofluoresceinografia/tendências , Inibidores da Angiogênese/uso terapêutico , Ceratite/terapia
16.
Perspect. nutr. hum ; 10(2): 165-175, jul.-dic. 2008. tab
Artigo em Espanhol | LILACS | ID: lil-595379

RESUMO

Introducción: la desnutrición afecta principalmente a los niños menores de cinco años. El Instituto Colombiano de Bienestar Familiar (ICBF) desarrolla, entre otros, algunos programas que buscan impactar positivamente en el estado nutricional de los menores de cinco años. Objetivo: describir el estado nutricional (según indicadores antropométricos), hematológico y parasitario de dos grupos de niños de los programas de Hogares Comunitarios (HC) y Desayunos Infantiles (DI) pertenecientes al ICBF en el centro zonal 4 de Medellín. Materiales y métodos: estudio descriptivo de corte en 164 menores de cinco años. Los datos se recolectaron mediante encuestas, peso corporal de los niños, estatura/longitud y toma de sangre y análisis coprológico. Resultados: 47,1% de la muestra eran niños, con edad promedio de tres años; 56,6% de los menores pertenecían al estrato 1, mayormente entre los niños de HC. El promedio del peso corporal fue 14,4 kg, sin diferencias estadísticas entre los grupos; 45% de los niños presentaron riesgo de desnutrición crónica, global el 32% de los menores y aguda el 14%, sin diferencias entre los dos grupos. De acuerdo a lo esperado para la edad el 21% de los menores tenía disminución de la hemoglobina y 11% del hematocrito. En la comparación de los grupos no hubo diferencias significativas de los parámetros hematológicos. En el 66,7% de los niños se encontraron parásitos intestinales, principalmente Giardia lamblia. Conclusión: se encontró un importante porcentaje de niños con desnutrición y anemia, que refleja la necesidad de fortalecer tanto los programas, como la educación de los menores y las familias, así como las condiciones sociales y económicas, los cuales influyen en la salud de la población evaluada y en su estado nutricional.


Malnutrition is a condition affecting mostly children younger than five years. ICBF supports many nutritional programs, which is trying to improve the nutritional status for children younger than 5 five years. Objective: describe nutritional status related to a hematological condition and parasitic infections in two groups of children participating in programs such as the “Hogares comunitarios” (HC) and “Desayunos Infantiles” (DI) supported by the ICBF in zone 1 Medellin-Colombia. Methods: it is a cross-sectional study, 164 children were recruted, data was collected, applying questionnaires, anthropometric measurements, and evaluating blood and stool samples. Results: 47,1% of the subjects were boys, mean age was 3 years, 56,6% of the children were in the lowest social economic level, mainly children participating in HC program. The average for weight was 14,4kg, no statistical significant differences between groups were found, but 45% of the children classified for chronic malnutrition risk, 32% for global malnutrition and 14% for acute malnutrition. According to the age 21% of the population studied had low hemoglobin level and 11% has low hematocrit level. No significant statistics between groups for hematological markers were found. Parasitic infection was present in 67%, they were mainly infected by Giardia lamblia. Conclusion: malnutrition and anemia was prevalent in this population. It is necessary to encourage and support programs that should benefit children and their families, improving education and social economic conditions could help to improve their nutritional status.


Assuntos
Criança , Anemia , Programas de Nutrição Aplicada , Transtornos da Nutrição Infantil , Enteropatias Parasitárias , Desnutrição , Estado Nutricional , Fenômenos Fisiológicos da Nutrição do Lactente
17.
Bioresour Technol ; 99(7): 2141-7, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17624772

RESUMO

The effects of amendment with municipal solid waste compost (MSWC) and sewage sludge (SS) on acid-base properties of soil humic acids (HAs) were investigated. For this purpose, HAs were isolated from MSWC and SS and two different Portuguese soils, one sandy and the other clay loam, either unamended or amended with MSWC or SS at a rate of 60 t ha(-1), and analysed by potentiometric titrations at various ionic strengths (0.01, 0.05, 0.1 and 0.3M) over the pH range from 3.5 to 10.5. All titration data were fitted with the NICA-Donnan model and the variations of model parameters between the various HA samples were discussed. The HAs from MSWC and SS had lower acidic functional group contents and higher proton binding affinities than the control soil HAs. Amending soils with MSWC and SS determined a decrease of acidic functional group contents and an increase on proton binding affinities of soil HAs. These effects were more evident in SS-amended soil HAs than in MSWC-amended soil HAs, and in clay loam soil HA than in sandy soil HA.


Assuntos
Substâncias Húmicas/análise , Esgotos , Solo , Silicatos de Alumínio , Argila , Concentração de Íons de Hidrogênio , Prótons , Dióxido de Silício , Termodinâmica
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