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1.
Molecules ; 28(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37175211

RESUMO

Obesity is characterized by the excessive accumulation of fat, which triggers a low-grade chronic inflammatory process. Currently, the search for compounds with anti-obesogenic effects that help reduce body weight, as well as associated comorbidities, continues. Among this group of compounds are plant extracts and flavonoids with a great diversity of action mechanisms associated with their beneficial effects, such as anti-inflammatory effects and/or as signaling molecules. In the bark of Tabebuia rosea tree, there are different classes of metabolites with anti-inflammatory properties, such as quercetin. Therefore, the present work studied the effect of the ethanolic extract of T. rosea and quercetin on the mRNA of inflammation markers in obesity compared to the drugs currently used. Total RNA was extracted from epididymal adipose tissue of high-fat diet-induced obese Wistar rats treated with orlistat, phentermine, T. rosea extract, and quercetin. The rats treated with T. rosea and quercetin showed 36 and 31% reductions in body weight compared to the obese control, and they likewise inhibited pro-inflammatory molecules: Il6, Il1b, Il18, Lep, Hif1a, and Nfkb1 without modifying the expression of Socs1 and Socs3. Additionally, only T. rosea overexpressed Lipe. Both T. rosea and quercetin led to a reduction in the expression of pro-inflammatory genes, modifying signaling pathways, which led to the regulation of the obesity-inflammation state.


Assuntos
Fármacos Antiobesidade , Tabebuia , Ratos , Animais , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Ratos Wistar , Quercetina/metabolismo , Extratos Vegetais/uso terapêutico , Obesidade/etiologia , Obesidade/induzido quimicamente , Tecido Adiposo/metabolismo , Peso Corporal , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Dieta Hiperlipídica/efeitos adversos
2.
Nefrologia (Engl Ed) ; 42(4): 448-459, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36402686

RESUMO

INTRODUCTION: Patients with advanced chronic kidney disease (ACKD) have a high prevalence of malnutrition. The dietary restrictions that we usually apply in terms of macro and micronutrients force our patients to follow dietary guidelines that deviate from healthy patterns. OBJETIVES: To determine if a personalized nutritional intervention program, minimizing the usual restrictions would be justified in case it improved the evolution of kidney disease compared to standard treatment. SECUNDARY OBJETIVES: To determine changes in nutrient intakes and in anthropometric and biochemical parameters, as well as quantify episodes of hyperkalemia. MATERIAL AND METHODS: A single-center, randomized and controlled educational intervention clinical trial was conduct in patients from the ERCA outpatients clinic at the Complejo Hospitalario Universitario de Albacete. 75 patients were included, assigning 35 to a Control group and 40 to the Intervention group with 1-year follow-up. The nutritional status was determined using anthropometric data, body composition by Bioimpedance, blood and urine biochemical parameters and a 24-h recall questionnaire. The nutritional intervention was carried out in three different ways: individual, collective and telephone recall. RESULTS: At the beginning of the study, the BMI showed a situation of weight excess with a mean of 28.83 kg/m2 (5.4) in men and 26.96 kg/m2 (4.09) in women. 70% of our patients had overweight. The abdominal circumference was 105.3 cm (10.2) and 92.3 cm (13.7) for men and women respectively without significant changes throughout the study. The percentage of fat mass (FM) was high in both groups for men and women throughout the study. We did not find biochemical parameters of malnutrition and only significant differences were observed in glomerular filtration rate (GFR), which increased in the intervention group. No patient presented any episodes of hyperkalemia during the study. The energy intake in both groups showed an inadequate distribution of macronutrients with a poor intake of carbohydrates (CH) that was supplemented with an excess of fat. In the case of micronutrients, we did observe an increase in potassium and fiber intakes with a decrease in sodium and phosphorus in the intervention group. CONCLUSIONS: Malnutrition is not exclusively an intake defficit and encompasses both the problems derived from a deficit and an excess of nutrients intake. Un to 70% of our patients showed weight excess and a fat mass higher than desirable. The implementation of an individualized nutritional education program, including a vegetables and fiber rich diet, less atherogenic, not only did not cause electrolyte alterations but also slowed the progression of kidney disease.


Assuntos
Hiperpotassemia , Desnutrição , Insuficiência Renal Crônica , Masculino , Humanos , Feminino , Insuficiência Renal Crônica/terapia , Taxa de Filtração Glomerular , Micronutrientes , Desnutrição/etiologia
3.
Skin Appendage Disord ; 8(6): 486-491, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36407646

RESUMO

Introduction: Refractory cases of alopecia areata (AA) may be considered a therapeutic challenge. Intralesional methotrexate (IL-MTX) has been used in other dermatological diseases rather than AA. Likewise, its topical use as an immunosuppressant drug may be of interest for the control of the lymphoid infiltrate in AA. On the other hand, the use of fractional ablative laser is supported in literature as an alternative or complementary treatment in AA, whilst the generation of columns of thermal damage may favour the migration of cells and cytokines that are beneficial. Case Presentation: In this paper, we present 2 cases in which IL-MTX and ablative fractional CO2 laser were combined with excellent outcomes. Conclusion: Previous research encompasses a total of 23 patients. Most patients presented with patchy AA. The doses administered ranged from 2.5 to 50 mg with an average frequency of 3 weeks. On average, most patients required a minimum of 3 sessions. One case employed 1% topical methotrexate ointment. Adverse local events were mild and transient. In conclusion, the concomitant application of these treatments has not been reported previously. Specific recommendations relating to the appropriate dosing of the drug, frequency of administration, and requirements for analytical control studies should be determined in further studies.

4.
Front Med (Lausanne) ; 9: 991873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160152

RESUMO

Background: It has been proposed that polyphenols can be used in the development of new therapies against COVID-19, given their ability to interfere with the adsorption and entrance processes of the virus, thus disrupting viral replication. Seeds from Caesalpinia spinosa, have been traditionally used for the treatment of inflammatory pathologies and respiratory diseases. Our team has obtained an extract called P2Et, rich in polyphenols derived from gallic acid with significant antioxidant activity, and the ability to induce complete autophagy in tumor cells and reduce the systemic inflammatory response in animal models. Methods: In this work, a phase II multicenter randomized double-blind clinical trial on COVID-19 patients was designed to evaluate the impact of the P2Et treatment on the clinical outcome and the immunological parameters related to the evolution of the disease. The Trial was registered with the number No. NCT04410510*. A complementary study in an animal model of lung fibrosis was carried out to evaluate in situ lung changes after P2Et in vivo administration. The ability of P2Et to inhibit the viral load of murine and human coronaviruses in cellular models was also evaluated. Results: Patients treated with P2Et were discharged on average after 7.4 days of admission vs. 9.6 days in the placebo group. Although a decrease in proinflammatory cytokines such as G-CSF, IL-15, IL-12, IL-6, IP10, MCP-1, MCP-2 and IL-18 was observed in both groups, P2Et decreased to a greater extent G-CSF, IL-6 and IL-18 among others, which are related to lower recovery of patients in the long term. The frequency of T lymphocytes (LT) CD3+, LT double negative (CD3+CD4-CD8-), NK cells increased in the P2Et group where the population of eosinophils was also significantly reduced. In the murine bleomycin model, P2Et also reduced lung inflammation and fibrosis. P2Et was able to reduce the viral replication of murine and human coronaviruses in vitro, showing its dual antiviral and anti-inflammatory role, key in disease control. Conclusions: Taken together these results suggest that P2Et could be consider as a good co-adjuvant in the treatment of COVID-19. Clinical trail registration: https://clinicaltrials.gov/ct2/show/NCT04410510, identifier: NCT04410510.

5.
BMJ Lead ; 6(3): 186-191, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36170481

RESUMO

AIM: To explore the views of an international sample of nursing and midwifery managers concerning attributes that they associate with compassionate management. METHOD: A cross-sectional online survey. Using a snowballing sampling method, 1217 responses were collected from nursing and midwifery managers in 17 countries. A total of complete 933 responses to a question related to which actions and behaviours indicated that a manager was exercising compassionate leadership were analysed for this paper. First, content analysis of the responses was conducted, and second, a relative distribution of the identified themes for the overall sample and for each participating country was calculated. RESULTS: Six main themes were identified describing the attributes of a compassionate leader: (1) Virtuous support, (2) Communication, (3) Personal virtues of the manager, (4) Participatory communication, (5) Growth/flourishing/ nurturing and (6) Team cohesion. The first three themes mentioned above collectively accounted for 63% of the responses, and can therefore be considered to be the most important characteristics of compassionate management behaviour. CONCLUSION: The key indicators of compassionate management in nursing and midwifery which were identified emphasise approachability, active and sensitive listening, sympathetic responses to staff members' difficulties (especially concerning child and other caring responsibilities), active support of and advocacy for the staff team and active problem solving and conflict resolution. While there were differences between the countries' views on compassionate healthcare management, some themes were widely represented among different countries' responses, which suggest key indicators of compassionate management that apply across cultures.


Assuntos
Liderança , Tocologia , Estudos Transversais , Empatia , Feminino , Humanos , Gravidez , Inquéritos e Questionários
6.
Artigo em Inglês | MEDLINE | ID: mdl-35627597

RESUMO

The aim of this study was to evaluate the effects of Tetraselmis chuii (TC) microalgae supplementation for sixty days on hematological, anthropometric and hormonal parameters in healthy young men. Forty-six men divided into a placebo group (PG; n = 16; 20.77 ± 2.7 years; 72.14 ± 7.18 kg; 1.76 ± 0.07 m), a group supplemented with 25 mg/day of TC (SG 25; n = 15; 20.40 ± 1.40 years; 71.28 ± 8.26 kg; 1.76 ± 0.05 m) and another group supplemented with 200 mg/day of TC (SG 200; n = 15; 20.83 ± 2.45 years; 72.30 ± 11.13 kg; 1.77 ± 0.08 m) participated in this double-blind study. PG ingested 200 mg/day of lactose powder. Participants underwent 4 assessments (baseline, month 1, month 2 and desadaptation) separated in time by an interval of thirty days. At SG 25 and SG 200, significant increases in percent muscle mass, erythropoietin, insulin-like growth factor 1, free testosterone, leukocytes, neutrophils and lymphocytes were observed (p < 0.05). Decreases in the levels of percent fat mass, platelets, hematocrit and mean corpuscular hemoglobin also occurred in these groups (p < 0.05). TC supplementation induced favorable changes on anthropometric, hematological and hormonal levels. In view of the data, it seems that the most effective dose was 25 mg/day of TC.


Assuntos
Clorófitas , Microalgas , Antropometria , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Masculino
7.
Am J Surg Pathol ; 46(6): 765-773, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34985047

RESUMO

Cervical clear cell carcinoma (CCC) is a rare human papillomavirus-independent adenocarcinoma. While recent studies have focused on gastric-type endocervical adenocarcinoma (GTA), little is known about CCC. A total of 58 (CCCs) were collected from 14 international institutions and retrospectively analyzed using univariable and multivariable methods and compared with 36 gastric-type adenocarcinomas and 173 human papillomavirus-associated (HPVA) endocervical adenocarcinoma (ECA) regarding overall survival (OS) and recurrence-free survival (RFS). Most cases were FIGO stage I (72.4%), with Silva C pattern of invasion (77.6%), and the majority were treated with radical surgery (84.5%) and adjuvant therapy (55.2%). Lymphovascular invasion was present in 31%, while lymph node metastasis was seen in 24.1%; 10.3% were associated with abdominopelvic metastases at the time of diagnosis; 32.8% had recurrences, and 19% died of disease. We did not find statistically significant differences in OS and RFS between CCC and GTA at 5 and 10 years (P=0.313 and 0.508, respectively), but there were significant differences in both OS and RFS between CCC and HPVA ECA (P=0.003 and 0.032, respectively). Also, OS and RFS in stage I clear cell and GTA were similar (P=0.632 and 0.692, respectively). Multivariate analysis showed that OS is influenced by the presence of recurrence (P=0.009), while RFS is influenced by the FIGO stage (P=0.025). Cervical CCC has poorer outcomes than HPVA ECA and similar outcomes to human papillomavirus-independent GTA. Oncologic treatment significantly influences RFS in univariate analysis but is not an independent prognostic factor in multivariate analysis suggesting that alternative therapies should be investigated.


Assuntos
Adenocarcinoma de Células Claras , Alphapapillomavirus , Carcinoma , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Carcinoma/patologia , Colo do Útero/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Papillomaviridae , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia
8.
Nefrologia (Engl Ed) ; 2021 Aug 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34393001

RESUMO

INTRODUCTION: Patients with advanced chronic kidney disease (ACKD) have a high prevalence of malnutrition. The dietary restrictions that we usually apply in terms of macro and micronutrients force our patients to follow dietary guidelines that deviate from healthy patterns. OBJECTIVES: To determine if a personalized nutritional intervention program, minimizing the usual restrictions would be justified in case it improved the evolution of kidney disease compared to standard treatment. SECONDARY OBJECTIVES: To determine changes in nutrient intakes and in anthropometric and biochemical parameters, as well as quantify episodes of hyperkalemia. MATERIAL AND METHODS: A single-center, randomized and controlled educational intervention clinical trial was conduct in patients from the ERCA outpatients clinic at the Complejo Hospitalario Universitario de Albacete. 75 patients were included, assigning 35 to a Control group and 40 to the Intervention group with 1-year follow-up. The nutritional status was determined using anthropometric data, body composition by Bioimpedance, blood and urine biochemical parameters and a 24-h recall questionnaire. The nutritional intervention was carried out in three different ways: individual, collective and telephone recall. RESULTS: At the beginning of the study, the BMI showed a situation of weight excess with a mean of 28.83 kg/m2 (5.4) in men and 26.96 kg/m2 (4.09) in women. 70% of our patients had overweight. The abdominal circumference was 105.3 cm (10.2) and 92.3 cm (13.7) for men and women respectively without significant changes throughout the study. The percentage of fat mass (FM) was high in both groups for men and women throughout the study. We did not find biochemical parameters of malnutrition and only significant differences were observed in glomerular filtration rate (GFR), which increased in the intervention group. No patient presented any episodes of hyperkalemia during the study. The energy intake in both groups showed an inadequate distribution of macronutrients with a poor intake of carbohydrates (CH) that was supplemented with an excess of fat. In the case of micronutrients, we did observe an increase in potassium and fiber intakes with a decrease in sodium and phosphorus in the intervention group. CONCLUSIONS: Malnutrition is not exclusively an intake deficit and encompasses both the problems derived from a deficit and an excess of nutrients intake. Un to 70% of our patients showed weight excess and a fat mass higher than desirable. The implementation of an individualized nutritional education program, including a vegetables and fiber rich diet, less atherogenic, not only did not cause electrolyte alterations but also slowed the progression of kidney disease.

9.
J Transcult Nurs ; 32(6): 765-777, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33899614

RESUMO

INTRODUCTION: Despite the importance of compassionate leadership in health care, many of the existing publications do not account for the effect of culture. The aim of this study is to explore the views of nursing and midwifery managers from different countries in relation to the definition, advantages, and importance of compassion. METHODOLOGY: A cross-sectional, descriptive, exploratory online survey was conducted across 17 countries, containing both closed and open-ended questions. Data from N = 1,217 respondents were analyzed using a directed hybrid approach focusing only on qualitative questions related to compassion-giving. RESULTS: Four overarching themes capture the study's results: (1) definition of compassion, (2) advantages and importance of compassion for managers, (3) advantages and importance of compassion for staff and the workplace, and (4) culturally competent and compassionate leadership. DISCUSSION: Innovative research agendas should pursue further local qualitative empirical research to inform models of culturally competent and compassionate leadership helping mangers navigate multiple pressures and be able to transculturally resonate with their staff and patients.


Assuntos
Empatia , Tocologia , Estudos Transversais , Atenção à Saúde , Feminino , Humanos , Liderança , Gravidez
11.
Planta ; 250(4): 1177-1189, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31190117

RESUMO

MAIN CONCLUSION: A MAPK module, of which MPK6 kinase is an important component, is involved in the coordination of the responses to Pi and Fe in the primary root meristem of Arabidopsis thaliana. Phosphate (Pi) deficiency induces determinate primary root growth in Arabidopsis through cessation of cell division in the meristem, which is linked to an increased iron (Fe) accumulation. Here, we show that Mitogen-Activated Protein Kinase6 (MPK6) has a role in Arabidopsis primary root growth under low Pi stress. MPK6 activity is induced in roots in response to low Pi, and such induction is enhanced by Fe supplementation, suggesting an MPK6 role in coordinating Pi/Fe balance in mediating root growth. The differentiation of the root meristem induced by low Pi levels correlates with altered expression of auxin-inducible genes and auxin transporter levels via MPK6. Our results indicate a critical role of the MPK6 kinase in coordinating meristem cell activity to Pi and Fe availability for proper primary root growth.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Ferro/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatos/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Transporte Biológico , Divisão Celular , Genes Reporter , Ácidos Indolacéticos/metabolismo , Meristema/enzimologia , Meristema/genética , Meristema/crescimento & desenvolvimento , Proteínas Quinases Ativadas por Mitógeno/genética , Reguladores de Crescimento de Plantas , Raízes de Plantas/enzimologia , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Estresse Fisiológico
12.
Dermatol Ther ; 32(3): e12892, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30958613

RESUMO

Hailey-Hailey disease (HHD) or chronic benign familial pemphigus is an autosomal dominant genodermatosis with complete penetrance characterized by painful vesicles, erosions, and macerated intertriginous skin. We present a 66-year-old woman with a personal 35-year history of pruritic recurrent vesicles and erosions in both axillae and inguinal folds. HHD was confirmed by cutaneous biopsy. Past treatments had failed, including topical corticosteroids, antibiotics and oral doxycycline, minocycline, dapsone, and acitretin. Phototherapy and intralesional injection of toxin botulinum A was performed in the axillae. The patient was started on naltrexone 6.25 mg nightly. Six weeks later, complete clearing was observed. At typical doses, naltrexone blocks µ and δ opiod receptors, thereby blocking the union of ß-endorphins at those sites. Paradoxically, at low doses, the partial binding to those receptors leads to a homeostatic increase of opioid receptors and an upregulation of endogenous opioids. Low-dose naltrexone (LDN) may also exert an anti-inflammatory action through its antagonist effect on toll-like receptor 4 found on macrophages. We consider that LDN is an effective and safe alternative for the HHD, representing an important progress in the management of this disease with limited therapeutic options.


Assuntos
Naltrexona/uso terapêutico , Pênfigo Familiar Benigno/tratamento farmacológico , Idoso , Feminino , Humanos
13.
Int J Mol Sci ; 19(8)2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30126113

RESUMO

Endometrial cancer (EC) is the most common malignancy of the genital tract among women in developed countries. Recently, a molecular classification of EC has been performed providing a system that, in conjunction with histological observations, reliably improves EC classification and enhances patient management. Patient-derived xenograft models (PDX) represent nowadays a promising tool for translational research, since they closely resemble patient tumour features and retain molecular and histological features. In EC, PDX models have already been used, mainly as an individualized approach to evaluate the efficacy of novel therapies and to identify treatment-response biomarkers; however, their uses in more global or holistic approaches are still missing. As a collaborative effort within the ENITEC network, here we describe one of the most extensive EC PDX cohorts developed from primary tumour and metastasis covering all EC subtypes. Our models are histologically and molecularly characterized and represent an excellent reservoir of EC tumour samples for translational research. This review compiles the information on current methods of EC PDX generation and their utility and provides new perspectives for the exploitation of these valuable tools in order to increase the success ratio for translating results to clinical practice.


Assuntos
Neoplasias do Endométrio/patologia , Endométrio/patologia , Animais , Modelos Animais de Doenças , Descoberta de Drogas/métodos , Neoplasias do Endométrio/tratamento farmacológico , Endométrio/efeitos dos fármacos , Feminino , Humanos , Transplante de Neoplasias/métodos , Medicina de Precisão/métodos , Pesquisa Translacional Biomédica/métodos , Transplante Heterólogo/métodos
14.
PLoS One ; 12(2): e0172574, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28231262

RESUMO

During wound healing, skin function is restored by the action of several cell types that undergo differentiation, migration, proliferation and/or apoptosis. These dynamics are tightly regulated by the evolution of the extra cellular matrix (ECM) contents along the process. Pharmacologically active flavonoids have shown to exhibit useful physiological properties interesting in pathological states. Among them, oleanolic acid (OA), a pentacyclic triterpene, shows promising properties over wound healing, as increased cell migration in vitro and improved wound resolution in vivo. In this paper, we pursued to disclose the molecular mechanisms underlying those effects, by using an in vitro scratch assay in two epithelial cell lines of different linage: non-malignant mink lung epithelial cells, Mv1Lu; and human breast cancer cells, MDA-MB-231. In every case, we observed that OA clearly enhanced cell migration for in vitro scratch closure. This correlated with the stimulation of molecular pathways related to mitogen-activated protein (MAP) kinases, as ERK1,2 and Jun N-terminal kinase (JNK) 1,2 activation and c-Jun phosphorylation. Moreover, MDA-MB-231 cells treated with OA displayed an altered gene expression profile affecting transcription factor genes (c-JUN) as well as proteins involved in migration and ECM dynamics (PAI1), in line with the development of an epithelial to mesenchymal transition (EMT) status. Strikingly, upon OA treatment, we observed changes in the epidermal growth factor receptor (EGFR) subcellular localization, while interfering with its signalling completely prevented migration effects. This data provides a physiological framework supporting the notion that lipophilic plant extracts used in traditional medicine, might modulate wound healing processes in vivo through its OA contents. The molecular implications of these observations are discussed.


Assuntos
Movimento Celular/efeitos dos fármacos , Ativadores de Enzimas/farmacologia , Células Epiteliais/efeitos dos fármacos , Receptores ErbB/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ácido Oleanólico/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Receptores ErbB/agonistas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
15.
Reumatol. clín. ; 12(6): 319-322, nov.-dic. 2016. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-157432

RESUMO

Objetivo. Evaluar la eficacia y la seguridad a corto plazo del tratamiento de pacientes con artritis reumatoide (AR) con rituximab (RTX) comparado con un anti-TNF (2TNF) tras retirada de un primer anti-TNF. Métodos. Estudio multicéntrico prospectivo, observacional, de práctica clínica de pacientes con AR grave refractaria a anti-TNF que recibieron RTX comparados con los que recibieron un 2TNF. Comparación de las variables de eficacia y respuesta EULAR buena/moderada a los 6 meses. Resultados. Ciento tres pacientes incluidos; 82 alcanzan seguimiento a 6 meses, 73,7% mujeres. Datos basales grupo RTX y 2TNF, respectivamente: 8,6 y 6,6 NAD, 8,8 y 7,5 NAI, 5,45 ± 1,28 y 5,18 ± 1,21 en DAS28 (p=0,048), 41 y 38,7mmHg de VSG, y 1,2 y 1,0 en HAQ. Mejoría en todos los parámetros en ambos grupos sin diferencias significativas (excepto mayor reducción de VSG con RTX). Ausencia de efectos adversos graves. Conclusiones. El uso de RTX en segunda línea de terapia biológica tras fallo a un primer anti-TNF en práctica clínica muestra mejoría en las variables de eficacia y funcionalidad a los 6 meses, sin presentar efectos adversos graves. Estos resultados no difieren de los observados tras el uso de un segundo anti-TNF en el mismo escenario clínico (AU)


Objective. to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. Methods. prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. Results. 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. Conclusions. RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Artrite Reumatoide/tratamento farmacológico , Rituximab/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Terapia Biológica/métodos , Terapia Biológica , Resultado do Tratamento , Avaliação de Eficácia-Efetividade de Intervenções , Estudos Prospectivos , Consentimento Livre e Esclarecido/normas , Relação Dose-Resposta a Droga , Inquéritos e Questionários
16.
Immunopharmacol Immunotoxicol ; 38(5): 353-63, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27367537

RESUMO

CONTEXT: There is evidence that n-3 polyunsaturated fatty acids (n-3-PUFAs) can inhibit mTORC1, which should potentiate autophagy and eliminate NLRP3 inflammasome activity. OBJECTIVE: Evaluate the effect of a high-fat or high-fat/fructose diet with and without n-3-PUFAs on hepatic gene expression. MATERIALS AND METHODS: We examined the mRNA expression by RT-PCR of Mtor, Nlrp3, and other 22 genes associated with inflammation in rats livers after a 9-week diet. The dietary regimens were low-fat (control, CD), high-fat (HF), high-fat/fructose (HF-Fr), and also each of these supplemented with n-3-PUFAs (CD-n-3-PUFAs, HF-n-3-PUFAs, and HF-Fr-n-3-PUFAs). These data were processed by GeneMania and STRING databases. RESULTS: Compared to the control, the HF group showed a significant increase (between p < 0.05 and p < 0.0001) in 20 of these genes (Il1b, Il18, Rxra, Nlrp3, Casp1, Il33, Tnf, Acaca, Mtor, Eif2s1, Eif2ak4, Nfkb1, Srebf1, Hif1a, Ppara, Ppard, Pparg, Mlxipl, Fasn y Scd1), and a decrease in Sirt1 (p < 0.05). With the HF-Fr diet, a significant increase (between p < 0.05 and p < 0.005) was also found in the expression of 16 evaluated genes (Srebf1, Mlxipl, Rxra, Abca1, Il33, Nfkb1, Hif1a, Pparg, Casp1, Il1b, Il-18, Tnf, Ppard, Acaca, Fasn, Scd1), along with a decrease in the transcription of Mtor and Elovl6 (p < 0.05). Contrarily, many of the genes whose expression increased with the HF and HF-Fr diets did not significantly increase with the HF-n-3-PUFAs or HF-Fr-n-3-PUFAs diet. DISCUSSION AND CONCLUSION: We found the interrelation of the genes for the mTORC1 complex, the NLRP3 inflammasome, and other metabolically important proteins, and that these genes respond to n-3-PUFAs.


Assuntos
Gorduras na Dieta/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Frutose/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamassomos/imunologia , Fígado/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , RNA Mensageiro/imunologia , Serina-Treonina Quinases TOR/imunologia , Animais , Regulação da Expressão Gênica/imunologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Complexos Multiproteicos/imunologia , Ratos , Ratos Sprague-Dawley
17.
J Thromb Thrombolysis ; 41(3): 544-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26036227

RESUMO

Congenital plasminogen deficiency is a rare autosomal recessive disorder, characterized by chronic mucosal membranous lesions. Although the most common clinical manifestation is eye involvement as ligneous conjunctivitis, extra-ocular lesions affecting other mucosal surfaces indicates a systemic disease. In this report we describe two cases with atypical extra-ocular involvement that includes pericarditis and recurrent hematocolpos, and one with paradoxical correlation between ocular lesions and plasminogen levels. In ligneous conjunctivitis, although different treatment strategies have been tried with mild success, the only effective therapy is topical or systemic plasminogen concentrates that are not commercially available. Unfortunately there is not either effective management for cases with multisystemic disease. Hence, treatment for plasminogen deficiency is still a challenge and the variability of the clinical spectrum in this pathology makes necessary a multidisciplinary approach.


Assuntos
Transtornos Herdados da Coagulação Sanguínea , Plasminogênio/administração & dosagem , Plasminogênio/deficiência , Transtornos Herdados da Coagulação Sanguínea/sangue , Transtornos Herdados da Coagulação Sanguínea/tratamento farmacológico , Transtornos Herdados da Coagulação Sanguínea/genética , Transtornos Herdados da Coagulação Sanguínea/patologia , Pré-Escolar , Conjuntivite/sangue , Conjuntivite/tratamento farmacológico , Conjuntivite/genética , Conjuntivite/patologia , Feminino , Hematocolpia/sangue , Hematocolpia/tratamento farmacológico , Hematocolpia/genética , Hematocolpia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pericardite/sangue , Pericardite/tratamento farmacológico , Pericardite/genética , Pericardite/patologia
18.
FEM (Ed. impr.) ; 18(4): 269-274, jul.-ago. 2015. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-142691

RESUMO

INTRODUCCIÓN: La infección respiratoria aguda es un problema de salud pública en menores de 5 años; la detección e identificación tempranas de sus signos disminuye la mortalidad en este grupo de edad y es una meta de la formación médica. OBJETIVO: Comparar en estudiantes de medicina el método educativo tradicional y el escenario simulado para el reconocimiento de signos de enfermedad respiratoria aguda en niños de 2 meses a 5 años. SUJETOS Y MÉTODOS: Se realizó un ensayo clínico para estudiantes de medicina, aleatorizados en dos grupos: A (clase teórica y ayudas audiovisuales) y B (escenario simulado). El desenlace primario fue el desempeño en la evaluación global. Se realizó prueba de Mann-Withney Wilcoxon para comparación entre grupos y Mann-Withney Wilcoxon pareada para análisis intragrupo (antes y después de la intervención). RESULTADOS: Mediante prueba de Mann-Withney Wilcoxon pareada intragrupo pre y postintervención, el grupo A mostró mejor un desarrollo de competencias en el desenlace primario (p = 0,02) y en la evaluación global del escenario simulado (p = 0,04). El grupo B logró cambios significativos en el desenlace primario (p = 0,00), la anamnesis (p = 0,00) y la evaluación global del escenario simulado (p = 0,00). En la evaluación postintervención no se encontraron diferencias significativas en el desenlace primario ni secundario. CONCLUSIONES. La comparación postintervención entre los grupos A y B no mostró diferencias significativas en ninguna de las variables estudiadas entre ambos grupos


INTRODUCTION: The acute respiratory infection is a public health problem in children under 5 years of age. The early detection and identification of its signs reduces the mortality rates in these age groups and is an objective in medical education. AIM. To compare the traditional teaching method with the simulated-scenario teaching method in the acquisition of skills necessary to recognize respiratory distress in children between 2 months and 5 years of age by medical students. SUBJECTS AND METHODS: A clinical trial was done for medical students and they were divided into two randomized groups: group A which used the traditional teaching method and group B, which used the simulated-scenario method. The primary outcomes were seen in the global evaluation performances. A Mann-Withney Wilcoxon test was used for the comparison among groups and a paired Mann-Withney Wilcoxon test was used for the intra-group analysis (before and after the intervention). RESULTS: When using the paired Mann-Withney Wilcoxon intragroup test pre and post intervention, group A showed a better skill development in the primary outcome (p = 0.02) and the global evaluation in simulated scenario (p = 0.04). On the other hand, group B reached significant changes on the primary outcomes (p = 0.00), anamnesis (p = 0.00) and global evaluation with the simulated-scenario method (p = 0.00). It was observed that in the post-intervention evaluation there weren’t any significant differences between the primary and secondary outcomes. CONCLUSIONS: The post-intervention comparison between groups A and B didn’t show significant differences in the studied variables between both groups


Assuntos
Humanos , /métodos , Educação Médica/métodos , Síndrome Respiratória Aguda Grave/diagnóstico , Transtornos Respiratórios/diagnóstico , Insuficiência Respiratória/diagnóstico , Doenças Respiratórias/diagnóstico , Simulação por Computador , Modelos Teóricos , Avaliação de Sintomas/métodos , Diagnóstico Diferencial
19.
Endocrine ; 45(1): 98-105, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23546614

RESUMO

The aim of this study was to evaluate the effect of long-chain omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on metabolic state and gene expression in subcutaneous adipose tissues of obese adolescents. Obese adolescents (n = 26, 10 girls and 16 boys) aged 12.4 ± 2.1 years were assigned to a 12-week regimen of n-3 PUFA intake. Five times per day, subjects received a food supplement consisting of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (3 g per day, 944 mg EPA, and 2,088 mg DHA). Blood parameters were measured, and subcutaneous adipose tissue biopsies were analyzed to determine gene expression at baseline and after 12 weeks. Student's t test and the Wilcoxon signed-rank test were used to estimate differences in arithmetic means of pre- and post-dietary supplementation for various anthropometric, biochemical, clinical, and gene expression parameters. After 12 weeks, n-3 PUFA consumption was associated with decreased body mass index (29.7 ± 4.6 vs. 27.8 ± 4.4 kg/m(2); P < 0.001), waist circumference (93.2 ± 9.9 vs. 90.5 ± 10.0 cm; P < 0.003), hip circumference (102.9 ± 10.9 vs. 101.1 ± 10.9 cm; P < 0.014), and blood triglyceride levels (220.8 ± 27.4 vs. 99.7 ± 32.7 mg/dL; P < 0.001). Fatty acid supplementation/n3 PUFA supplementation was associated with a downregulated expression of the genes encoding PPARγ and PGC-1α (P < 0.001), and an upregulated expression of the genes encoding PPARα (P < 0.007) and SREBP1 (P < 0.021). The expressions of SOD2 (P < 0.04), CAT (P < 0.001), GPX3 (P < 0.032) and HIF-1α protein also decreased. Our study demonstrated that n-3 PUFA consumption and dietary restriction improved the anthropometric parameters and decreased the triglycerides levels of the adolescents, suggesting a reduction in hypoxia in subcutaneous adipose tissue.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , PPAR alfa/genética , PPAR gama/genética , Obesidade Infantil , Gordura Subcutânea/efeitos dos fármacos , Adolescente , Criança , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , PPAR alfa/metabolismo , PPAR gama/metabolismo , Obesidade Infantil/dietoterapia , Obesidade Infantil/genética , Obesidade Infantil/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Gordura Subcutânea/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
Ginecol Obstet Mex ; 80(9): 563-80, 2012 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-23243836

RESUMO

BACKGROUND: According to data from the World Health Organization and UNICEF from year 2009, iron deficiency is the most widespread nutritional deficiency worldwide. This deficiency causes an imbalance between needs and iron supply, which consequently results in anemia. Around the world, two million people suffer from anemia, half of which is due to iron deficiency. The most impacted groups are children and teenagers, due to their highest requirements derived from the growing process, and women in their reproductive age, due to their loss of iron derived from menstruating or to their highest iron needs during pregnancy. This increase in needs is not satisfied by the regular diet, since it includes an insufficient amount and/or low bioavailability of iron. PURPOSE: To share with the medical community treating pregnant women the experience of an expert group so that they always bear in mind the repercussions caused by anemia during pregnancy, know more about the diagnostic possibilities and have a reference point for prescribing iron supplements. METHOD: The consensus method was used through the expert panel group technique. Two rounds were taken for structuring the clinical questions. The first one was to facilitate working groups their focusing in the clinical topics and the population of interest; the second one was to aid in posing specific questions observing the Patient, Intervention, Compare and Outcome (PICO) structure. The primary and clinical secondary study variables were defined by the working groups from the previously developed questions and during the face-to-face working period, according to the natural history of the disease: risk factors, diagnostic classification, (either pharmacological or non pharmacological) treatment and prognosis. The level of evidence and clinical recommendation was classified based on the Evidence Classification Level and Clinical Recommendation of the Medicine Group based on Evidence from Oxford University. RESULTS: In Mexico, 20.6% of pregnant women suffer from anemia, especially those between 15 and 16 years old, who prevail in 42.4% and 34.3% percent, respectively. Almost half the cases are due to iron deficiency. This type of anemia is associated with a higher risk of pre-term delivery, of low birth weight and perinatal death. The first assessment of an anemic pregnant woman shall include the medical history, a physical examination and the quantification of the erythrocyte indices, serum concentrations of iron and ferritin. The measurement of this last one has the highest sensitivity and specificity for diagnosing iron deficiency. Daily oral iron supplementation, at a 60-to-120 mg dosage, may correct most of mild-to-moderate anemias. The most appropriate treatment is with iron salts (iron sulfate, polimaltose iron complex or iron fumarate). In case of intolerance to iron sulfate or fumarate, polimaltose iron is a better tolerated option. Treatment shall be administered until the hemoglobin values are > 10.5 g and ferritin is between 300 and 360 microg/dL, and such levels shall be observed for at least one year. Parenteral administration is an alternative for patients with a severe intolerance to oral administration; even when the possibility of anaphylaxis shall be considered it is lower when using ferrous sacarate. Transfusion is reserved for patients with hemoglobin lower than 7 g/dL or having an imminent cardio-respiratory decompensation. CONCLUSIONS: Iron deficiency is the highest prevailing nutritional deficiency worldwide and its consequences during pregnancy may be highly risky for both the mother and her child. Anemia diagnosis may easily be achieved through a blood analysis including the serum ferritin determination. Serum iron measurement shall not be used as the only marker to set the diagnosis. It is important to rule out other causes, in addition to the deficiencies, which produce anemia in a patient. It is essential to suggest the administration of iron supplements not only during the antenatal period but also after birth o even after a miscarriage to fulfill the need for depleted iron. In severe anemias (hemoglobin being lower than 9.0 g/L), iron doses higher than 120 mg a day may be required. Treatment shall always begin orally, and if this is not well tolerated, parenteral administration shall be used.


Assuntos
Anemia/diagnóstico , Anemia/tratamento farmacológico , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/tratamento farmacológico , Adolescente , Adulto , Anemia/classificação , Anemia/epidemiologia , Anemia/etiologia , Anemia/terapia , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/etiologia , Anemia Ferropriva/terapia , Biomarcadores , Transfusão de Sangue , Medicina Baseada em Evidências , Feminino , Ferritinas/sangue , Morte Fetal/etiologia , Doenças Fetais/etiologia , Doenças Fetais/prevenção & controle , Ácido Fólico/administração & dosagem , Ácido Fólico/uso terapêutico , Saúde Global , Hemoglobinas/análise , Humanos , Recém-Nascido , Ferro/administração & dosagem , Ferro/efeitos adversos , Ferro/sangue , Ferro/uso terapêutico , Ferro da Dieta/farmacocinética , México/epidemiologia , Pessoa de Meia-Idade , Cuidado Pós-Natal/métodos , Cuidado Pós-Natal/normas , Gravidez , Complicações Hematológicas na Gravidez/classificação , Complicações Hematológicas na Gravidez/epidemiologia , Complicações Hematológicas na Gravidez/etiologia , Complicações Hematológicas na Gravidez/terapia , Cuidado Pré-Natal/métodos , Cuidado Pré-Natal/normas , Prevalência , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
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