Phytochemical Study of Eryngium cymosum F. Delaroche and the Inhibitory Capacity of Its Main Compounds on Two Glucose-Producing Pathway Enzymes.

One undescribed acylated flavonol glucoside and five known compounds were isolated from the aerial parts of Eryngium cymosum F. Delaroche, a plant that is used in traditional Mexican medicine to treat type 2 diabetes. The chemical structures of the isolated compounds were elucidated using a variety of spectroscopic techniques, including 1D and 2D nuclear magnetic resonance (NMR) and mass spectrometry (MS). Chlorogenic acid (1), rosmarinic acid (2), caffeic acid (3), protocatechuic acid (4), kaempferol-3-O-(2,6-di-O-trans-ρ-coumaryl)-ß-d-glucopyranoside (5), and the new acylated flavonol glucoside quercetin-3-O-(2,6-di-O-trans-ρ-coumaryl)-ß-d-glucopyranoside (6) were isolated. This is the first report on the natural occurrence of quercetin-3-O-(2,6-di-O-trans-ρ-coumaryl)-ß-D-glucopyranoside (6). In addition, according to the HPLC profile obtained for the water extract (WE), chlorogenic acid (1) and rosmarinic acid (2) were identified as the main compounds, while kaempferol-3-O-(2,6-di-O-trans-ρ-coumaryl)-ß-d-glucopyranoside (5) were the main compound in the butanolic extract. We demonstrate the important role of compound 5 over the inhibition of G6Pase and FBPase. The isolated compounds may play an important role in the hypoglycemic effect of the extract and may act in a synergic way, but more experiments are needed to corroborate these findings.

Impact of Spirulina maxima Intake and Exercise (SIE) on Metabolic and Fitness Parameters in Sedentary Older Adults with Excessive Body Mass: Study Protocol of a Randomized Controlled Trial.

Life expectancy has increased unprecedentedly in recent decades, benefiting the longevity of the world's population. The most frequent pathological conditions presented in this age group include excessive body fat, frailty, and hypercholesterolemia. These pathological characteristics condition general health and autonomy in adults to carry out their usual activities. In this sense, the search for a healthy lifestyle is necessary, consisting in a healthy diet that includes supplementation with nutraceuticals and the daily practice of physical activity. This study protocol aims to evaluate the independent and synergistic effect of 12 weeks of Spirulina maxima intake (5 g/day), with or without an exercise program on metabolic and fitness parameters of 52 sedentary older adults with excessive body mass in a double-blind, randomized, crossover, controlled trial design. The main findings from this trial will provide novel evidence for future interventions designed for the elderly population and the result will be disseminated through peer-reviewed journals and international meetings. ClinicalTrials.gov identification number: NCT04658875 (Effect of Spirulina maxima and Exercise on General Fitness and Blood Lipids in Older Adults).

Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis - 2016 update.

OBJECTIVE: To update the recommendations for the treatment of axial spondyloarthritis (axSpA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting, the 7 recommendations included in this document were discussed and updated. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication and the level of agreement among Portuguese Rheumatologists was anonymously assessed using an online survey. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching of biological therapies in patients with axSpA. In total, seven recommendations were produced. The first recommendation is a general statement indicating that biological therapy is not a first-line drug treatment option and should only be used after conventional treatment has failed. The second recommendation is also a general statement about the broad concept of axSpA adopted by these recommendations that includes both non-radiographic and radiographic axSpA. Recommendations 3 to 7 deal with the definition of active disease (including the recommended threshold of 2.1 for the Ankylosing Spondylitis Disease Activity Score [ASDAS] or the threshold of 4 [0-10 scale] for the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), conventional treatment failure (nonsteroidal anti-inflammatory drugs being the first-line drug treatment), assessment of response to treatment (based on an ASDAS improvement  of at least 1.1 units or a BASDAI improvement of at least 2 units [0-10 scale] or at least 50%), and strategy in the presence of an inadequate response (where switching is recommended) or in the presence of long-term remission (where a process of biological therapy optimization can be considered, either a gradual increase in the interval between doses or a decrease of each dose of the biological therapy). CONCLUSION: These recommendations may be used for guidance in deciding which patients with axSpA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

PORTUGUESE RECOMMENDATIONS FOR THE USE OF BIOLOGICAL THERAPIES IN PATIENTS WITH PSORIATIC ARTHRITIS--2015 UPDATE.

OBJECTIVE: To update recommendations for the treatment of psoriatic arthritis with biological therapies, endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting the 16 recommendations included in this document were discussed and updated. The level of agreement among Portuguese Rheumatologists was assessed using an online survey. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with psoriatic arthritis (PsA). Specific recommendations were developed for several disease domains: peripheral arthritis, axial disease, enthesitis and dactylitis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Aspectos nutricionales de la disfunción tiroidea en niños y adolescentes con síndrome de Down / Nutritional aspects of thyroid dysfunction in children and adolescents with down syndrome

La trisomía 21 o síndrome de Down (SD) es la causa más frecuente de retardo mental de origen cromosómico, asociada con disfunción tiroidea (DT) y obesidad como problema de salud pública. El hipotiroidismo es la forma más común de DT asociada con SD, con prevalencia cercana a 50%. Objetivo: Determinar la prevalencia de disfunción de tiroidea y aspectos relacionados con el estado nutricional de niños y adolescentes con SD. Métodos: Se realizó un estudio prospectivo y transversal, en 17 niños con SD (11,5 ± 3,0 años), seleccionados aleatoriamente. El estudio empleo evaluación antropométrica, entrevista dietética con recordatorio de 72 horas y determinación de hormonas tiroideas. El análisis estadístico requirió SPSS 17, con 95% IC, p <0,05. Resultados: Individuos con SD presentaron sobrepeso en 47,1% (n=8). Se observó hipotiroidismo subclínico en 71,4% (n=10), mientras que 28,6% (n=4) mostraron hipotiroidismo clínico. El consumo de yodo (53,4 ± 12,0 vs 130,5 ± 18,1; p<0,05), fenilalanina (0,1 ± 0,0 vs 2,3 ± 0,5; p<0,05) y tirosina (0,1 ± 0,0 vs 2,3 ± 0,5; p<0,05) fue bajo comparado con la media de requerimientos para estos nutrientes tiroideos en niños y adolescentes con SD. El consumo de yodo y concentraciones de T4 (r=0,512; p<0,03) mostraron correlación positiva; asimismo, el consumo de fenilalanina y tirosina (r=0,803; p<0,001). Conclusiones: Los trastornos de organificación de hormonas tiroideas en SD no justifican la DT. Se sugiere suplementación nutricional en etapas precoces de la vida, facilitando un estado eutiroideo que propicie el desarrollo físico y cognitivo en individuos con SD. Palabras clave: Síndrome de Down, disfunción tiroidea, nutrición, niños, adolescentes.

Trisomy 21 or Down Syndrome (DS) is the most common cause of mental retardation with chromosomal origin, associated with thyroid dysfunction (TD) and obesity as a public health problem. Hypothyroidism is the most common form of TD associated with DS, with nearly 50% prevalence. Objective: To determine the prevalence of thyroid dysfunction and aspects related to the nutritional status of children and adolescents with DS. Methods: A prospective and cross-sectional study in 17 children with DS (11.5 ± 3.0 years) were randomly selected. The study anthropometric, dietary interview with 72 hours and determination of thyroid hormones was realized. The required statistical analysis SPSS 17 with 95% CI, p <0.05. Results: Individuals with DS were overweight in 47.1% (n = 8). Subclinical hypothyroidism was observed in 71.4% (n = 10), while 28.6% (n = 4) showed clinical hypothyroidism. The consumption of iodine (53.4 ± 12.0 vs 130.5 ± 18.1; p <0.05), phenylalanine (0.1 ± 0, 0 vs 2.3 ± 0.5; p <0.05) and tyrosine (0.1 ± 0.0 vs 2.3 ± 0.5; p <0.05) was low compared to the average requirement for these thyroid nutrients in children and adolescents with DS. Consumption of iodine and T4 concentrations (r = 0.512; p <0.03) showed positive correlation; Also, consumption of phenylalanine and tyrosine (r = 0.803; p <0.001). Conclusions: Organification disorders of thyroid hormones in DS does not justify the TD. Nutritional supplementation of thyroid nutrients providing a euthyroid condition that improves physical and cognitive development in individuals with DS is suggested.

2011 Portuguese recommendations for the use of biological therapies in patients with psoriatic arthritis.

OBJECTIVE: To develop recommendations for the treatment of psoriatic arthritis (PsA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. A draft of the recommendations was first circulated to all Portuguese rheumatologists and their suggestions were incorporated in the draft. At a national meeting the recommendations were discussed and all attending rheumatologists voted on the level of agreement for each recommendation. A second draft was again circulated before publication. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with PsA. Specific recommendations were developed for several disease domains: peripheral arthritis, axial disease, enthesitis and dactylitis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis--December 2011 update.

OBJECTIVE: To develop recommendations for the treatment of axial spondyloarthritis with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. A draft of the recommendations and supporting evidence was first circulated to all Portuguese rheumatologists and their suggestions were incorporated in the draft. Secondly, at a national meeting the recommendations were presented, discussed and revised. Finally, the document resulting from this meeting was again circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the recommendations. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with axial spondyloarthritis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with axial spondyloarthritis should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Portuguese guidelines for the use of biological agents in rheumatoid arthritis - March 2010 update.

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment should be considered in RA patients with a disease activity score 28 (DAS 28) superior to 3.2 despite treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 6 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, characterized by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of 0.6 in the DAS28 score. After 6 months of treatment response criteria is defined as a decrease of more than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).

Seed implant retention score predicts the risk of prolonged urinary retention after prostate brachytherapy.

PURPOSE: To risk-stratify patients for urinary retention after prostate brachytherapy according to a novel seed implant retention score (SIRS). PATIENTS AND METHODS: A total of 835 patients underwent transperineal prostate seed implant from March 1993 to January 2007; 197 patients had (125)I and 638 patients had (103)Pd brachytherapy. Four hundred ninety-four patients had supplemental external-beam radiation. The final downsized prostate volume was used for the 424 patients who had neoadjuvant hormone therapy. Retention was defined as reinsertion of a Foley catheter after the implant. RESULTS: Retention developed in 7.4% of patients, with an average duration of 6.7 weeks. On univariate analysis, implant without supplemental external-beam radiation (10% vs. 5.6%; p = 0.02), neoadjuvant hormone therapy (9.4% vs. 5.4%; p = 0.02), baseline alpha-blocker use (12.5% vs. 6.3%; p = 0.008), and increased prostate volume (13.4% vs. 6.9% vs. 2.9%, >45 cm(3), 25-45 cm(3), <25 cm(3); p = 0.0008) were significantly correlated with increased rates of retention. On multivariate analysis, implant without supplemental external-beam radiation, neoadjuvant hormone therapy, baseline alpha-blocker use, and increased prostate volume were correlated with retention. A novel SIRS was modeled as the combined score of these factors, ranging from 0 to 5. There was a significant correlation between the SIRS and retention (p < 0.0001). The rates of retention were 0, 4%, 5.6%, 9%, 20.9%, and 36.4% for SIRS of 0 to 5, respectively. CONCLUSIONS: The SIRS may identify patients who are at high risk for prolonged retention after prostate brachytherapy. A prospective validation study of the SIRS is planned.

The role of Slit-Robo signaling in the generation, migration and morphological differentiation of cortical interneurons.

Cortical interneurons in rodents are generated in the ventral telencephalon and migrate tangentially into the cortex. This process requires the coordinated action of many intrinsic and extrinsic factors. Here we show that Robo1 and Robo2 receptor proteins are dynamically expressed throughout the period of corticogenesis and colocalize with interneuronal markers, suggesting that they play a role in the migration of these cells. Analysis of Robo mutants showed a marked increase in the number of interneurons in the cortices of Robo1(-/-), but not Robo2(-/-), animals throughout the period of corticogenesis and in adulthood; this excess number of interneurons was observed in all layers of the developing cortex. Using BrdU incorporation in dissociated cell cultures and phosphohistone-3 labeling in vivo, we demonstrated that the increased number of interneurons in Robo1(-/-) mice is, at least in part, due to increased proliferation. Interestingly, a similar increase in proliferation was observed in Slit1(-/-)/Slit2(-/-) mutant mice, suggesting that cell division is influenced by Slit-Robo signaling mechanisms. Morphometric analysis of migrating interneurons in Robo1(-/-), Robo2(-/-) and Slit1(-/-)/Slit2(-/-), but not in Slit1(-/-) mice, showed a differential increase in neuronal process length and branching suggesting that Slit-Robo signaling also plays an important role in the morphological differentiation of these neurons.