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Pancreatic ductal adenocarcinoma (PDAC), the most prevalent form of pancreatic cancer, has a 5-year survival rate of 9 %. PDX1 is an important transcription factor for embryonic development of the pancreas, pancreatic endocrine lineage differentiation, and maintenance of mature pancreatic ß-cells. In PDAC patients, PDX1 expression is downregulated in tumor cells compared to adjacent non-tumoral tissue. On the other hand, a higher PDX1 expression has been shown to improve the overall survival rate in PDAC patients. Therefore, our aim was to analyze the role of PDX1 on the phenotype of PDAC cells. To induce PDX1 expression, PANC-1 cells, derived from a human PDAC tumor, were treated with BRD7552 (a PDX1 inducer). Overexpression of PDX1 was confirmed by Western Blot analysis and no cytotoxic effects were observed by MTT reduction or Trypan Blue exclusion assays. Cell confluence assay and BrdU incorporation assay showed a significant reduction in proliferation rate in treated cells, while no differences were observed on the proportion of Ki67+ and PH3+ cells by immunostaining. In addition, cell cycle analysis by propidium iodide staining followed by flow cytometry showed an arrest in the G1 phase of the cell cycle of treated cells. Additionally, treated cells showed a significant reduction in migration rate. Furthermore, to assess the in ovo effects of BRD7552, treated PANC-1 cells were implanted onto the chorioallantoic membrane (CAM) of chick embryos and tumor size was measured at different time points, revealing a significant reduction in tumor growth of treated cells. Therefore, in this study we observed that a pharmacological induction of PDX1 in PANC-1 cells affects cell cycle, reduces proliferation rate and inhibits migratory potential in vitro. These findings were corroborated in ovo, where PDX1 overexpression diminished tumor growth of PANC-1 cells. In conclusion, the overexpression of PDX1 induced by BRD7552 drives PANC-1 cells to a less proliferative and migratory phenotype.
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Carcinoma Ductal Pancreático , Proteínas de Homeodomínio , Neoplasias Pancreáticas , Transativadores , Animais , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Transativadores/metabolismo , Transativadores/genética , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Embrião de Galinha , Humanos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Membrana Corioalantoide/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Modelos Animais de DoençasRESUMO
Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in therapy due to their anti-inflammatory and analgesic properties. However, their clinical use is often associated with gastrointestinal complications. Thus, this study aimed to investigate the protective effect of a sulfated iota-carrageenan isolated from the marine alga Solieria filiformis (IC-Sf) against naproxen-induced gastrointestinal injury. Methods: Parameters of gastrointestinal injury, secretory and motor functions, and toxicity were evaluated. Results: The results demonstrated that IC-Sf significantly reduced naproxen-induced gastrointestinal macroscopic injury, with a maximum effect observed at 30 mg/kg. IC-Sf also preserved gastrointestinal antioxidant defense and prevented lipid peroxidation, with a reduction in the non-protein sulfhydryl group (NP-SH) and malondialdehyde (MDA) concentrations induced by naproxen. Additionally, IC-Sf mitigated naproxen-induced gastrointestinal inflammation, as evidenced by reduced myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß). IC-Sf did not alter gastric secretion or gastrointestinal motility. In addition, the animals treated with IC-Sf did not present toxic effects. Conclusions: In conclusion, IC-Sf protected the gastrointestinal tract against the harmful effects of naproxen by inhibiting the inflammatory response and lipid peroxidation, suggesting its potential as a new therapeutic agent or food additive.
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PURPOSE: Multitarget kinase inhibitors (MKIs) are effective options in the treatment of cancer, significantly increasing the progression-free survival (PFS) of many tumors. Data about severity and prevalence of metabolic adverse events is scarce and may be significant in patients with a better survival. The aim of this study was to investigate glucose and lipids values of patients treated with lenvatinib. Secondary aims included evaluating changes in the estimated risk of cardiovascular disease and the relationship between metabolic alterations and tumor response to therapy. METHODS: A retrospective pilot study on 29 patients with advanced differentiated thyroid cancer was conducted. Clinical and biochemical characteristics were collected at the day of therapy initiation and follow up. The 10-year risk of cardiovascular disease was estimated with the SCORE2 and SCORE2-OP algorithms. Tumor burden change was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: No differences in glucose values were observed. A significant increase in total cholesterol (208 ± 41 versus 245 ± 67 mg/dl), triglycerides (112 [interquartile range, 58-326] versus 157 [78-296] mg/dl), calculated LDL cholesterol (128 [66-204] versus 140 [81-308] mg/dl) and cardiovascular risk was observed from baseline to follow up. Furthermore, these parameters increase progressively with increasing tumor response to therapy. CONCLUSIONS: Despite limitations, this study shows an association between the use of lenvatinib and the development of lipid alterations in patients with advanced thyroid cancer. However, further investigation is necessary for a more comprehensive understanding of the adverse metabolic profile of MKIs.
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BACKGROUND: Patient-reported outcomes (PROs) play a crucial role in cancer clinical trials. Despite the availability of validated PRO measures (PROMs), challenges related to low completion rates and missing data remain, potentially affecting the trial results' validity. This review explored strategies to improve and maintain high PROM completion rates in cancer clinical trials. METHODOLOGY: A scoping review was performed across Medline, Embase and Scopus and regulatory guidelines. Key recommendations were synthesized into categories such as stakeholder involvement, study design, PRO assessment, mode of assessment, participant support, and monitoring. RESULTS: The review identified 114 recommendations from 18 papers (16 peer-reviewed articles and 2 policy documents). The recommendations included integrating comprehensive PRO information into the study protocol, enhancing patient involvement during the protocol development phase and in education, and collecting relevant PRO data at clinically meaningful time points. Electronic data collection, effective monitoring systems, and sufficient time, capacity, workforce and financial resources were highlighted. DISCUSSION: Further research needs to evaluate the effectiveness of these strategies in various context and to tailor these recommendations into practical and effective strategies. This will enhance PRO completion rates and patient-centred care. However, obstacles such as patient burden, low health literacy, and conflicting recommendations may present challenges in application.
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Ensaios Clínicos como Assunto , Neoplasias , Medidas de Resultados Relatados pelo Paciente , Humanos , Neoplasias/terapia , Projetos de Pesquisa/normasRESUMO
Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination.
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COVID-19 , Imunidade Humoral , Humanos , Inibidores de Checkpoint Imunológico , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Complexo Antígeno-Anticorpo , Anticorpos AntiviraisRESUMO
Glioblastoma (GBM) is a life-threatening disease that presents high morbidity and mortality. The standardized treatment protocol results in a global survival of less than three years in the majority of cases. Immunotherapies have gained wide recognition in cancer treatment; however, GBM has an immunosuppressive microenvironment diminishing the possible effectiveness of this therapy. In this sense, investigating the inflammatory settings and the tumoral nature of GBM patients are an important goal to create an individual plan of treatment to improve overall survival rate and quality of life of these patients. Thirty-two patients who underwent surgical resection of GBM were included in this study. Tumor samples and 10 mL of peripheral blood were collected and immediately frozen. TNF-a, IL-1a and IL-4 were evaluated in the tumor and TNF-a, IL-1a and TGF-b in the plasma by Luminex assay. Immunohistochemistry analysis to determine immune celular profile was done, including immunohistochemistry for CD20, CD68 and CD3. Three cases were excluded. Tumor topography, tumor nature, and tumor volume reconstructions were accurately analyzed by T1-weighted, T2-weighted, and FLAIR magnetic resonance imaging. We found that GBM patients with below median peripheral levels of TNF-a and IL-1a had a decreased survival rate when compared to above median patients. On the other hand, patients with below median peripheral levels of TGF-b increased overall survival rate. Intratumoral IL-1a above median was associated with higher number of macrophages and fewer with B cells. Furthermore, plasmatic TNF-a levels were correlated with intratumoral TNF-a levels, suggesting that peripheral cytokines are related to the tumoral microenvironment. Even though tumor size has no difference regarding survival rate, we found a negative correlation between intratumoral IL-4 and tumor size, where larger tumors have less IL-4 expression. Nevertheless, the tumoral nature had a significant effect in overall survival rate, considering that infiltrative tumors showed decreased survival rate and intratumoral TNF-a. Moreover, expansive tumors revealed fewer macrophages and higher T cells. In multiple variation analyzes, we demonstrated that infiltrative tumors and below median peripheral IL-1a expression represent 3 times and 5 times hazard ratio, respectively, demonstrating a poor prognosis. Here we found that peripheral cytokines had a critical role as prognostic tools in a small cohort of GBM patients.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Citocinas , Qualidade de Vida , Interleucina-4 , Prognóstico , Microambiente TumoralRESUMO
Tumor DNA has been detected in body fluids of cancer patients. Somatic tumor mutations are being used as biomarkers in body fluids to monitor chemotherapy response as a minimally invasive tool. In this study, we evaluated the potential of tracking somatic mutations in free DNA of plasma and urine collected from Wilms tumor (WT) patients for monitoring treatment response. Wilms tumor is a pediatric renal tumor resulting from cell differentiation errors during nephrogenesis. Its mutational repertoire is not completely defined. Thus, for identifying somatic mutations from tumor tissue DNA, we screened matched tumor/leukocyte DNAs using either a panel containing 16 WT-associated genes or whole-exome sequencing (WES). The identified somatic tumor mutations were tracked in urine and plasma DNA collected before, during and after treatment. At least one somatic mutation was identified in five out of six WT tissue samples analyzed. Somatic mutations were detected in body fluids before treatment in all five patients (three patients in urine, three in plasma, and one in both body fluids). In all patients, a decrease of the variant allele fraction of somatic mutations was observed in body fluids during neoadjuvant chemotherapy. Interestingly, the persistence of somatic mutations in body fluids was in accordance with clinical parameters. For one patient who progressed to death, it persisted in high levels in serial body fluid samples during treatment. For three patients without disease progression, somatic mutations were not consistently detected in samples throughout monitoring. For one patient with bilateral disease, a somatic mutation was detected at low levels with no support of clinical manifestation. Our results demonstrated the potential of tracking somatic mutations in urine and plasma DNA as a minimally invasive tool for monitoring WT patients. Additional investigation is needed to check the clinical value of insistent somatic mutations in body fluids.
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DNA de Neoplasias/genética , Neoplasias Renais/genética , Mutação , Tumor de Wilms/genética , Alelos , Quimioterapia Adjuvante , Pré-Escolar , DNA de Neoplasias/sangue , DNA de Neoplasias/urina , Feminino , Humanos , Lactente , Neoplasias Renais/sangue , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/urina , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Terapia Neoadjuvante , Sequenciamento do Exoma , Tumor de Wilms/sangue , Tumor de Wilms/tratamento farmacológico , Tumor de Wilms/urinaRESUMO
Resumen Objetivo: determinar los valores séricos de la enzima lecitina colesterol aciltransferasa en un grupo de mujeres postmenopáusicas, y establecer su relación con factores asociados a riesgo cardiovascular. Materiales y métodos: estudio descriptivo transversal prospectivo, correlacional, que incluyó 56 mujeres postmenopáusicas en quienes se evaluaron variables antropométricas y bioquímicas (perfil lipídico y glicemia basal) asociadas a riesgo cardiovascular y se correlacionaron con las concentraciones séricas de lecitina colesterol aciltransferasa. Resultados: los valores séricos promedio de dicha enzima fueron 7,89 ± 1,26 (g/ml. Las mujeres con valores de índice de masa corporal superior a 25 tienen niveles séricos de lecitina colesterol aciltransferasa significativamente mayores que aquellas que tienen índice de masa corporal normal. No se observaron relaciones significativas entre los niveles de lecitina colesterol aciltransferasa y las variables bioquímicas evaluadas. Conclusiones: este trabajo es uno de los primeros que evalúa los niveles séricos de lecitina colesterol aciltransferasa en mujeres postmenopáusicas del Caribe colombiano. Se encontró una relación significativa entre los niveles séricos de lecitina colesterol aciltransferasa y los valores de índice de masa corporal elevados. Se requieren nuevos estudios para entender mejor la relación entre los niveles séricos de lecitina colesterol aciltransferasa y el riesgo cardiovascular en mujeres postmenopáusicas.
Abstract Objective: To determine the serum levels of lecithin cholesterol acyltransferase in a group of postmenopausal women and to establish their relationship with factors associated with cardiovascular risk. Materials and methods: A descriptive, correlational and cross-sectional study was performed that included 56 postmenopausal women. Anthropometric and biochemical (lipid profile and baseline blood glucose) variables associated with cardiovascular risk were measured, and were correlated with the serum concentrations of lecithin cholesterol acyltransferase. Results: The mean serum level of lecithin cholesterol acyltransferase was 7.89 ± 1.26 (g/ml. The women with a body mass index greater than 25 had significantly higher serum levels of the enzyme than those that had a normal body mass index. No significant relationships were observed between the levels of lecithin cholesterol acyltransferase and the biochemical variables evaluated. Conclusions: This study is one of the first that has evaluated the serum levels of lecithin cholesterol acyltransferase in postmenopausal women of the Colombian Caribbean. A significant relationship was found between the serum levels of lecithin cholesterol acyltransferase and elevated values of the body mass index. Further studies are required for a better understanding of the relationship between the serum levels of lecithin cholesterol acyltransferase and cardiovascular risk in postmenopausal women.
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Humanos , Feminino , Pessoa de Meia-Idade , Pós-Menopausa , Fatores de Risco de Doenças Cardíacas , Fosfatidilcolina-Esterol O-Aciltransferase , Arteriosclerose , Doenças Cardiovasculares , DislipidemiasRESUMO
PURPOSE: The aim of the study was to describe the spontaneous TSH level variations and levothyroxine dose adjustments in athyreotic patients with differentiated thyroid cancer (DTC) in real-life practice. METHODS: Patients with DTC were retrospectively evaluated at a tertiary referral center between October 2006 and November 2013. Hormone measurements (TSH and FT4 serum levels), L-T4 prescription information (dose per kg per day) and other medications were recorded at 1 month and 3, 12, 24, 36 and 48 months after primary treatment (surgery ± radioiodine therapy). RESULTS: The cohort was composed of 452 patients; about 20% of patients with stable levothyroxine dose have clinically meaningful spontaneous TSH variations (defined as ΔTSH > 2 mcUI/mL) at yearly follow-up visit. Furthermore, about 25% of athyreotic DTC patients with stable dose have a ΔTSH > 1.5 mcUI/mL and about 40% a ΔTSH > 1 mcUI/mL during each follow-up visit. We further investigated whether this TSH variation would lead to subsequent dose changes. About 19.9-37.7% of DTC patients on stable LT4 dose on the previous visit had their levothyroxine dose reduced, while 7.8-14.9% increased due to TSH variations. We further evaluated the decision to change the dose in relation with the age-specific TSH range. Up to 77.2% of patients had their dose adjusted due to TSH falling below the age-specific range. CONCLUSIONS: Spontaneous serum TSH variations determine levothyroxine replacement therapy in athyreotic patients with DTC, requiring multiple dose changes.
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Neoplasias da Glândula Tireoide/sangue , Tireoidectomia , Tireotropina/sangue , Tiroxina/uso terapêutico , Adulto , Relação Dose-Resposta a Droga , Feminino , Terapia de Reposição Hormonal , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tiroxina/administração & dosagem , Tiroxina/sangueRESUMO
PURPOSE: We investigated the feasibility of kilovoltage rotational radiotherapy for breast cancer (kV-EBRT) via Monte Carlo simulations and measurements on phantoms. METHODS: We derived the dose distributions for X-ray beams at 150â¯kV, 300â¯kVp and 320â¯kV irradiating breast cylindrical phantoms of 14â¯cm diameter, mimicking the pendant breast. Simulations were based on the Geant4 toolkit. The point-like X-ray source was rotated either over a full circle or on a limited arc around the phantom. We studied the influence on the surface dose of the distance between the tumor lesion to the skin, of the irradiation protocol (full scan or partial scan) and of the X-ray tube current modulation. RESULTS: Rotational kV-EBRT permitted a periphery-to-center dose ratio from 13% to 9% in homogeneous breast phantoms. Dose distributions in phantoms with off-center simulated lesions, showed a skin-to-tumor dose ratio of 16% and 34% for lesions at 3.25 and 5.25â¯cm from cylinder axis, respectively. Simulation of the X-ray tube current modulation during the rotation, permits to reach a dose ratio of 20% for the lesion located at 5.25â¯cm from phantom axis. CONCLUSIONS: We showed the possibility of using low-energy X-ray spectra for kV-EBRT with collimated beams, for obtaining a periphery-to-center dose ratio in the same order of conventional accelerator based megavoltage radiotherapy, when the irradiated area is localized in the center of the breast. For tumors localized near the breast border, we showed that the tube current modulation can be a good solution in order to reduce the skin-to-tumor dose ratio.
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Neoplasias da Mama/radioterapia , Método de Monte Carlo , Fantomas de Imageamento , Radioterapia/instrumentação , Rotação , Radiometria , Dosagem Radioterapêutica , Raios XRESUMO
El conflicto de intereses (CDI) surge cuando el interés primario de un profesional de la salud, que es el bienestar de los pacientes, ya sea a través de su atención directa o de otras actividades que generen y difundan conocimiento para mejorar esa atención, está en riesgo de ser sesgado por un interés secundario que ocasionaría un daño. Sin embargo, no siempre la existencia de conflicto implica que se altere una conducta o una decisión, ni que ello resulte en un daño(AU).
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Conflito de Interesses , Saúde , NutricionistasRESUMO
OBJECTIVE: Statin intolerance, whether real or perceived, is a growing issue in clinical practice. Our aim was to evaluate the effects of reduced-dose statin therapy complemented with nutraceuticals. METHODS: First phase: Initially, 53 type 2 diabetic statin-treated patients received a supplementation with fish oil (1.7 g EPA + DHA/day), chocolate containing plant sterols (2.2 g/day), and green tea (two sachets/day) for 6 weeks. Second phase: "Good responders" to supplementation were identified after multivariate analysis (n = 10), and recruited for a pilot protocol of statin dose reduction. "Good responders" were then provided with supplementation for 12 weeks: standard statin therapy was kept during the first 6 weeks and reduced by 50% from weeks 6-12. RESULTS: First phase: After 6 weeks of supplementation, plasma LDL-C (-13.7% ± 3.7, P = .002) and C-reactive protein (-35.5% ± 5.9, P = .03) were reduced. Analysis of lathosterol and campesterol in plasma suggested that intensity of LDL-C reduction was influenced by cholesterol absorption rate rather than its synthesis. Second phase: no difference was observed for plasma lipids, inflammation, cholesterol efflux capacity, or HDL particles after statin dose reduction when compared to standard therapy. CONCLUSIONS: Although limited by the small sample size, our study demonstrates the potential for a new therapeutic approach combining lower statin dose and specific dietary compounds. Further studies should elucidate "good responders" profile as a tool for personalized medicine. This may be particularly helpful in the many patients with or at risk for CVD who cannot tolerate high dose statin therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02732223.
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Dietoterapia/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Medicina de Precisão/métodos , Idoso , LDL-Colesterol/sangue , Suplementos Nutricionais , Esquema de Medicação , Feminino , Óleos de Peixe/administração & dosagem , Óleos de Peixe/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , MasculinoRESUMO
Selection pressures exerted on Staphylococcus aureus by host factors may lead to the emergence of mutants better adapted to the evolving conditions at the infection site. This study was aimed at identifying the changes that occur in S. aureus exposed to the host defense mechanisms during chronic osteomyelitis and evaluating whether these changes affect the virulence of the organism. Genome assessment of two S. aureus isolates collected 13 months apart (HU-85a and HU-85c) from a host with chronic osteomyelitis was made by whole genome sequencing. Agr functionality was assessed by qRT-PCR. Isolates were tested in a rat model of osteomyelitis and the bacterial load (CFU/tibia) and the morphometric osteomyelitic index (OI) were determined. The ability of the isolates to trigger the release of proinflammatory cytokines was determined on macrophages in culture. Persistence of S. aureus within the host resulted in an agrC frameshift mutation that likely led to the observed phenotype. The capacity to cause bone tissue damage and trigger proinflammatory cytokines by macrophages of the agr-deficient, unencapsulated derivative (HU-85c) was decreased when compared with those of the isogenic CP8-capsulated parental strain (HU-85a). By comparison, no significant differences were found in the bacterial load or the OI from rats challenged with isogenic Reynolds strains [CP5, CP8, and non-typeable (NT)], indicating that lack of CP expression alone was not likely responsible for the reduced capacity to cause tissue damage in HU-85c compared with HU-85a. The production of biofilm was significantly increased in the isogenic derivative HU-85c. Lack of agr-dependent factors makes S. aureus less virulent during chronic osteomyelitis and alteration of the agr functionality seems to permit better adaptation of S. aureus to the chronically infected host.
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Adaptação Biológica/genética , Proteínas de Bactérias/genética , Interações Hospedeiro-Patógeno , Mutação , Osteomielite/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Transativadores/genética , Animais , Carga Bacteriana , Biofilmes , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Ratos , Adulto JovemLILACS-Express
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ABSTRACT Piper caldense C. DC., Piperaceae, commonly known as "pimenta-d'água", "pimenta-darda" or "paguarandy" in Brazil, is a shrub that grows mainly in humid and shaded habitats. The present study investigates the anatomy of the leaves and stems of P. caldense by light and scanning electron microscopy in order to provide supporting data for correct identification of the species. The leaves are hypostomatic, have a 2-layered hypodermis, and posses pearl glands. The midrib shows a 'U'-shaped stele comprised of about ten collateral vascular bundles. The main anatomical marker of the stem is the presence of a continuous sclerenchymatous sheath in the pith. Two forms of calcium oxalate crystals, namely crystal sand and raphides, are observed in this species.
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Primary aldosteronism (PA) is one of the most frequent forms of secondary hypertension, associated with atherosclerosis and higher risk of cardiovascular events. Platelets play a key role in the atherosclerotic process. The aim of the study was to evaluate the platelet activation by measuring serum levels of soluble CD40L (sCD40L) and P-selectin (sP-selectin) in consecutive PA patients [subgroup: aldosterone-secreting adrenal adenoma (APA) and bilateral adrenal hyperplasia (IHA)], matched with essential hypertensive (EH) patients. The subgroup of APA patients was revaluated 6-months after unilateral adrenalectomy. In all PA group, we measured higher serum levels of both sP-selectin (14.29±9.33 pg/ml) and sCD40L (9.53±4.2 ng/ml) compared to EH patients (9.39±5.3 pg/ml and 3.54±0.94 ng/ml, respectively; p<0.001). After removal of APA, PA patients showed significant reduction of blood pressure (BP) values, plasma aldosterone (PAC) levels and ARR-ratio, associated with a significant reduction of sP-selectin (16.74±8.9 pg/ml vs. 8.1±3.8 pg/ml; p<0.01) and sCD40L (8.6±1 ng/ml vs. 5.24±0.94 ng/ml; p<0.001). In PA patients, we found a significant correlation between sP-selectin and sCD40L with PAC (r=0.52, p<0.01; r=0.50, p<0.01, respectively); this correlation was stronger in APA patients (r=0.54; p<0.01 r=0.63; p<0.01, respectively). Our results showed that PA is related to platelet activation, expressed as higher plasma values of sCD40L and sP-selectin values. Surgical treatment and consequent normalization of aldosterone secretion was associated with significant reduction of sCD40L and sP-selectin values in APA patients.
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Ligante de CD40/sangue , Hiperaldosteronismo/sangue , Selectina-P/sangue , Adenoma Adrenocortical/sangue , Adenoma Adrenocortical/urina , Aldosterona/urina , Antropometria , Feminino , Humanos , Hiperaldosteronismo/urina , Hipertensão/sangue , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , SolubilidadeRESUMO
Seaweeds are sources of diverse bioactive compounds, such as sulphated polysaccharides. This study was designed to evaluate the chemical composition and anti-diarrheal activity of a fraction of sulphated polysaccharide (PLS) obtained from the red seaweed Hypnea musciformis in different animal models, and to elucidate the underlying mechanisms. PLS was obtained by aqueous extraction, with a yield of 31.8% of the seaweed dry weight. The total carbohydrate content accounted for 99% of the sample. The sulfate content of the polysaccharide was 5.08% and the percentage of carbon was 25.98%. Pretreatment with all doses of PLS inhibited castor oil-induced diarrhea, with reduction of the total amount of stool, diarrheal stools, and the severity of diarrhea. PLS (90 mg/Kg) decreased castor oil- and PGE2-induced enteropooling. In addition, PLS (90 mg/Kg) increased the Na(+)/K(+)-ATPase activity in the small intestine and reduced gastrointestinal transit, possibly via activation of cholinergic receptors. Interestingly, the cholera toxin-induced fluid secretion and Cl(-) ion levels decreased in the intestinal contents of the animals pretreated with PLS (90 mg/kg), probably via reduction of toxin-GM1 receptor binding. In conclusion, PLS exerts anti-diarrheal activity by increasing Na(+)/K(+)-ATPase activity, inhibiting gastrointestinal motility, and blocking the toxin-GM1 receptor binding.
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Diarreia/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/farmacologia , Rodófitas/química , Sulfatos/química , Animais , Óleo de Rícino/efeitos adversos , Toxina da Cólera/toxicidade , Diarreia/induzido quimicamente , Diarreia/metabolismo , Diarreia/fisiopatologia , Feminino , Trânsito Gastrointestinal/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/fisiopatologia , Masculino , Camundongos , Antagonistas de Entorpecentes/farmacologia , Polissacarídeos/uso terapêutico , Ratos , Receptores de Superfície Celular/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
OBJECTIVE: This study aimed to identify markers of metabolic syndrome (MS) in patients with phenylketonuria (PKU). METHODS: This was a cross-sectional study consisting of 58 PKU patients (ages of 4-15 years): 29 patients with excess weight, and 29 with normal weight. The biochemical variables assessed were phenylalanine (phe), total cholesterol, HDL-c, triglycerides, glucose, and basal insulin. The patients had Homeostasis Model Assessment (HOMA) and waist circumference assessed. RESULTS: No inter-group difference was found for phe. Overweight patients had higher levels of triglycerides, basal insulin, and HOMA, but lower concentrations of HDL-cholesterol, when compared to the eutrophic patients. Total cholesterol/HDL-c was significantly higher in the overweight group. A positive correlation between basal insulin level and HOMA with waist circumference was found only in the overweight group. CONCLUSION: The results of this study suggest that patients with PKU and excess weight are potentially vulnerable to the development of metabolic syndrome. Therefore, it is necessary to conduct clinical and laboratory monitoring, aiming to prevent metabolic changes, as well as excessive weight gain and its consequences, particularly cardiovascular risk. .
OBJETIVO: Determinar marcadores bioquímicos da síndrome metabólica em pacientes com PKU. MÉTODOS: Foram avaliados dois grupos de pacientes com PKU, de quatro a 15 anos, com excesso de peso (29) e eutróficos (29). As variáveis bioquímicas avaliadas foram fenilalanina (phe), colesterol total, HDL-c, triglicérides, glicose e insulina basal. Foi determinado o Homa e mensurada a circunferência da cintura. RESULTADOS: As concentrações de phe, de colesterol total e de glicose foram equivalentes entre os grupos. Os pacientes com excesso de peso apresentaram maiores concentrações de triglicérides, de insulina basal, maiores valores da determinação do Homa, menores concentrações de HDL colesterol e valores mais elevados da relação do colesterol total/HDL-c. Houve correlação positiva entre a dosagem de insulina basal e do Homa com a circunferência da cintura nos pacientes do grupo com excesso de peso. CONCLUSÕES: Os resultados deste estudo sugerem que pacientes com PKU e excesso de peso são potencialmente vulneráveis ao desenvolvimento da síndrome metabólica. Há, portanto, necessidade de acompanhamento clínico-laboratorial que previna as alterações metabólicas, o ganho excessivo de peso e as suas consequências, em especial o risco cardiovascular. .
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Síndrome Metabólica/etiologia , Fenilalanina/sangue , Fenilcetonúrias/complicações , Biomarcadores/sangue , Glicemia/análise , Estudos Transversais , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Insulina/sangue , Síndrome Metabólica/sangue , Sobrepeso/sangue , Sobrepeso/complicações , Fenilcetonúrias/sangue , Fenilcetonúrias/dietoterapia , Fatores de Risco , Triglicerídeos/sangueRESUMO
AIM: To compare the body composition of overweight children and adolescents by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) before and after physical activity program. METHODS: One hundred and eleven patients with mean age (SD) of 12 (1.9) participated in the study. We assessed the weight, height, waist circumference (WC), and body composition by DXA and BIA. Patients underwent a program of diet and physical activity (1 h 30 min/day, 3 times a week for 3 months) and were evaluated before and after this period. RESULTS: Mean initial zBMI were 2.3 (0.5) and waist SDS 5.9 (1.8). Significant differences were observed when we compared the measurements taken by DXA and BIA, respectively: total body fat percentage (40 and 31.5) and fat-free mass (43.1 and 50.6 kg). Regarding the trunk fat by DXA, there was a positive correlation with the WC/height ratio (r = 0.65; p < 0.01). After the intervention period, we observed a reduction in the zBMI, waist SDS, and total body fat and increase of fat-free mass by DXA. BIA only detected reduction in fat. CONCLUSION: BIA underestimates the percentage of fat and overestimates fat-free mass in relation to DXA. There is positive correlation between trunk fat and the ratio WC/height. In addition, DXA detected changes in body composition induced by a short period of physical training, unlike BIA.
Assuntos
Composição Corporal/fisiologia , Dieta , Impedância Elétrica , Estilo de Vida , Atividade Motora , Sobrepeso/fisiopatologia , Absorciometria de Fóton/métodos , Adolescente , Estatura/fisiologia , Peso Corporal/fisiologia , Brasil , Criança , Feminino , Humanos , Masculino , Obesidade/diagnóstico por imagem , Obesidade/fisiopatologia , Obesidade/terapia , Sobrepeso/diagnóstico por imagem , Sobrepeso/terapia , Circunferência da Cintura/fisiologiaRESUMO
The introduction of nucleic acid amplification techniques (NAT) in blood banks was intended to reduce the residual risk of transfusion-transmitted infections. Co-circulation of a great diversity of HIV-1 variants in Argentina portrays the need to assess the sensitivity of serological and molecular assays available for their detection. In this study, we evaluated the sensitivity of the COBAS AmpliScreen™ HIV-1 Test, version 1.5 (Roche) for the detection of HIV-1 RNA in plasma samples of infected individuals from Argentina. The results of this study reveal that this technique has high sensitivity for the detection of HIV-1 RNA under assay conditions: using mini-pool testing, pools ≥ 50 RNA copies per ml achieved ≥ 92 % sensitivity, whereas in the standard procedure, samples ≥ 207 RNA copies/ml achieved 100 % sensitivity. Moreover, the COBAS AmpliScreen™ HIV-1 Test, version 1.5 (Roche) is suitable for detecting prevailing HIV-1 variants.