RESUMO
Creatine has been used to maximize resistance training effects on skeletal muscles, including muscle hypertrophy and fiber type changes. This study aimed to evaluate the impact of creatine supplementation on the myostatin pathway and myosin heavy chain (MyHC) isoforms in the slow- and fast-twitch muscles of resistance-trained rats. Twenty-eight male Wistar rats were divided into four groups: a sedentary control (Cc), sedentary creatine supplementation (Cr), resistance training (Tc), and resistance training combined with creatine supplementation (Tcr). Cc and Tc received standard commercial chow; Cr and Tcr received a 2% creatine-supplemented diet. Tc and Tcr performed a resistance training protocol on a ladder for 12 weeks. Morphology, MyHC isoforms, myostatin, follistatin, and ActRIIB protein expressions were analyzed in soleus and white gastrocnemius portion samples. The results were analyzed using two-way ANOVA and Tukey's test. Tc and Tcr exhibited higher performance than their control counterparts. Resistance training increased the ratio between muscle and body weight, the cross-sectional area, as well as the interstitial collagen fraction. Resistance training alone increased MyHC IIx and follistatin while reducing myostatin (p < 0.001) and ActRIIB (p = 0.040) expressions in the gastrocnemius. Resistance training induced skeletal muscle hypertrophy and interstitial remodeling, which are more evident in the gastrocnemius muscle. The effects were not impacted by creatine supplementation.
Assuntos
Creatina , Folistatina , Masculino , Ratos , Animais , Creatina/farmacologia , Cadeias Pesadas de Miosina , Miostatina , Ratos Wistar , Músculo Esquelético , Isoformas de Proteínas , Suplementos Nutricionais , Hipertrofia , Receptores de Antígenos de Linfócitos TRESUMO
NRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRASQ61-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRASQ61 mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRASQ61-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib.
Assuntos
Melanoma , Proteínas Proto-Oncogênicas B-raf , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Sorafenibe/farmacologia , Linhagem Celular Tumoral , Mutação , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Glicólise/genética , Glucose/metabolismo , Estresse Fisiológico , Fosfofrutoquinase-2/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismoRESUMO
BACKGROUND: Lately, there has been an increasing interest in using plant-derived proteins for wine phenolic fining. Proteins extracted from cereals, potatoes, and legumes have been proposed as effective fining agents, but only those from pea, wheat, and potatoes have been approved for their use in wine. This work aimed at determining the fining ability of quinoa (Chenopodium quinoa Willd.) protein extracts (QP), compared to commercial fining agents, on red wines. RESULTS: The trials compared the performance of QP (30 and 50 g/hL), two potato protein extracts and gelatin, at two different contact times (48 and 96 h), using Petit Verdot, Malbec, and Cabernet Sauvignon wines. Turbidity, total phenolics, precipitable tannins, catechins, and color characteristics were determined. QP reduced the turbidity of all wines in a similar way to commercial fining agents. Both doses of QP significantly reduced tannins and other phenolic measures, including color intensity reductions, in a similar way to commercial fining agents. CONCLUSION: QP behaved as an effective fining agent that deserves further studies in order to improve its performance and advance its characterization. © 2022 Society of Chemical Industry.
Assuntos
Chenopodium quinoa , Solanum tuberosum , Vitis , Gelatina , Fenóis , Proteínas de Plantas , Taninos/química , Vitis/químicaRESUMO
Spondyloarthritis and rheumatoid arthritis are classified as inflammatory arthritis and represent a significant source of pain and disability. Non-pharmacological intervention with physical exercise is among the therapeutic approaches most used by health professionals. This study aimed to investigate the effectiveness of aquatic exercise in the treatment of inflammatory arthritis. The review was registered on the PROSPERO (CRD42020189602). The databases (PubMed, PEDro, Web of Science, and SciELO) were searched for studies involving adults with inflammatory arthritis and subjected to rehabilitation with aquatic exercise compared to any other control group, from the year 2010 to March 2022. Pain, disease activity, and physical function were regarded as primary outcomes. Two reviewers completed the eligibility screening and data extraction, and disagreements were resolved by a third reviewer. The methodological quality was assessed using the PEDro scale. A total of 5254 studies were identified, and nine articles were included, totalling 604 participants. Regarding pain, two studies showed that aquatic exercise was superior to home exercise. One study showed that disease activity was significantly improved in the aquatic group compared to the land-based exercise and the control groups (no exercise). Two studies reported that therapy containing aquatic exercise was able to improve physical function. Overall, the studies included in this review indicate that aquatic exercise is effective in treating pain, disease activity, and physical function in individuals with inflammatory arthritis. However, further studies carrying stronger evidence should be conducted to determine whether the treatment with aquatic exercise is superior to other types of therapies.
Assuntos
Artrite Reumatoide , Hidroterapia , Adulto , Artrite Reumatoide/terapia , Exercício Físico , Terapia por Exercício , Humanos , Dor , Qualidade de VidaRESUMO
PURPOSE: The aim of this study was to determine the prevalence of distress and unmet supportive care needs in post-treatment colorectal cancer (CRC) survivors. Also, to explore the association between both variables and to identify potential associated sociodemographic and cancer-related risk factors. METHODS: A cross-sectional study of 200 CRC survivors who at least 1 month before had completed the primary treatment for CRC was conducted. The Brief Symptom Inventory-18 (BSI-18) and the Spanish version of Cancer Survivors' Unmet Needs (S-CaSUN) were used. RESULTS: One in five CRC survivors showed clinical distress and 86% expressed at least one unmet need. Distress was positively associated with the prevalence of needs in all domains. All comprehensive care and information needs were expressed by at least 20% of survivors and some by more than 50%. Other needs also mentioned by 20% of survivors were financial support, ongoing case manager, and concerns about cancer recurrence. The risk factors associated were lower socioeconomic status, younger age, and a primary treatment that includes more than surgery. CONCLUSIONS: The findings highlight the relevance of extending psychosocial care beyond the CRC primary medical treatment. A person-centered approach that addresses informational, emotional, social, and physical needs can increase satisfaction with care and also prevent psychological morbidity in CRC survivors.
Assuntos
Neoplasias Colorretais , Qualidade de Vida , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/terapia , Estudos Transversais , Necessidades e Demandas de Serviços de Saúde , Humanos , Prevalência , Inquéritos e QuestionáriosAssuntos
Animais , Ratos , Vitamina D , Remodelação Ventricular , Tiorredoxinas , Suplementos NutricionaisRESUMO
To investigate the role of NLRP3 inflammasome in cardiac aging, we evaluate here morphological and ultrastructural age-related changes of cardiac muscles fibers in wild-type and NLRP3-knockout mice, as well as studying the beneficial effect of melatonin therapy. The results clarified the beginning of the cardiac sarcopenia at the age of 12 months, with hypertrophy of cardiac myocytes, increased expression of ß-MHC, appearance of small necrotic fibers, decline of cadiomyocyte number, destruction of mitochondrial cristae, appearance of small-sized residual bodies, and increased apoptotic nuclei ratio. These changes were progressed in the cardiac myocytes of 24 old mice, accompanied by excessive collagen deposition, higher expressions of IL-1α, IL-6, and TNFα, complete mitochondrial vacuolation and damage, myofibrils disorganization, multivesicular bodies formation, and nuclear fragmentation. Interestingly, cardiac myocytes of NLRP3-/- mice showed less detectable age-related changes compared with WT mice. Oral melatonin therapy preserved the normal cardiomyocytes structure, restored cardiomyocytes number, and reduced ß-MHC expression of cardiac hypertrophy. In addition, melatonin recovered mitochondrial architecture, reduced apoptosis and multivesicular bodies' formation, and decreased expressions of ß-MHC, IL-1α, and IL-6. Fewer cardiac sarcopenic changes and highly remarkable protective effects of melatonin treatment detected in aged cardiomyocytes of NLRP3-/- mice compared with aged WT animals, confirming implication of the NLRP3 inflammasome in cardiac aging. Thus, NLRP3 suppression and melatonin therapy may be therapeutic approaches for age-related cardiac sarcopenia.
Assuntos
Remodelação Ventricular , Vitamina D , Animais , Suplementos Nutricionais , Ratos , TiorredoxinasRESUMO
Muscular aging is a complex process and underlying physiological mechanisms are not fully clear. In recent years, the participation of the NF-kB pathway and the NLRP3 inflammasome in the chronic inflammation process that accompanies the skeletal muscle's aging has been confirmed. microRNAs (miRs) form part of a gene regulatory machinery, and they control numerous biological processes including inflammatory pathways. In this work, we studied the expression of four miRs; three of them are considered as inflammatory-related miRs (miR-21, miR-146a, and miR-223), and miR-483, which is related to the regulation of melatonin synthesis, among other targets. To investigate the changes of miRs expression in muscle along aging, the impact of inflammation, and the role of melatonin in aged skeletal muscle, we used the gastrocnemius muscle of wild type (WT) and NLRP3-knockout (NLRP3-) mice of 3, 12, and 24 months-old, with and without melatonin supplementation. The expression of miRs and pro-caspase-1, caspase-3, pro-IL-1ß, bax, bcl-2, and p53, was investigated by qRT-PCR analysis. Histological examination of the gastrocnemius muscle was also done. The results showed that age increased the expression of miR-21 (p < 0.01), miR-146a, and miR-223 (p < 0.05, for both miRs) in WT mice, whereas the 24-months-old mutant mice revealed decline of miR-21 and miR-223 (p < 0.05), compared to WT age. The lack of NLRP3 inflammasome also improved the skeletal muscle fibers arrangement and reduced the collagen deposits compared with WT muscle during aging. For the first time, we showed that melatonin significantly reduced the expression of miR-21, miR-146a, and miR-223 (p < 0.05 for all ones, and p < 0.01 for miR-21 at 24 months old) in aged WT mice, increased miR-223 in NLRP3- mice (p < 0.05), and induced miR-483 expression in both mice strains, this increase being significant at 24 months of age.
RESUMO
BACKGROUND: The Cancer Survivors' Unmet Needs (CaSUN) measure is an assessment tool developed specifically for this population but several issues about its structural properties still remain unresolved. METHOD: The present study tests the theoretical model, the original authors' empirical solution, and a new rational proposal of the CaSUN using Confirmatory Factor Analysis. Reliability and convergent validity are also analysed. 566 Spanish breast cancer survivors completed the CaSUN, the Brief Symptom Inventory-18 (BSI-18) and the Quality of Life in Adult Cancer Survivors questionnaire (QLACS). RESULTS: The proposed model of five domains (physical effects, psychological effects, comprehensive care and information, practical issues, and relationships) plus a total score provided better fit than the authors' theoretical proposal and some advantages over their empirical proposal. Internal consistency (α = .73 - .95; r item-total > .30) and test-retest reliability (r = .74 - 89) were adequate. The CaSUN correlated with high emotional distress (r = .43 - .77) and poor quality of life (r = .18 - .64). CONCLUSIONS: The CaSUN-S is an effective and complete instrument that can help health professionals to collect data about the impact of the disease beyond the diagnosis and treatment phase that is important for patient care.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Adulto , Neoplasias da Mama/terapia , Feminino , Humanos , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Aging is a major risk for cardiovascular diseases (CVD). Age-related disorders include oxidative stress, mitochondria dysfunction, and exacerbation of the NF-κB/NLRP3 innate immune response pathways. Some of the molecular mechanisms underlying these processes, however, remain unclear. This study tested the hypothesis that NLRP3 inflammasome plays a role in cardiac aging and melatonin is able to counteract its effects. With the aim of investigating the impact of NLRP3 inflammasome and the actions and target of melatonin in aged myocardium, we analyzed the expression of proteins implied in mitochondria dynamics, autophagy, apoptosis, Nrf2-dependent antioxidant response and mitochondria ultrastructure in heart of wild-type and NLRP3-knockout mice of 3, 12, and 24 months-old, with and without melatonin treatment. Our results showed that the absence of NLRP3 prevented age-related mitochondrial dynamic alterations in cardiac muscle with minimal effects in cardiac autophagy during aging. The deficiency of the inflammasome affected Bax/Bcl2 ratio, but not p53 or caspase 9. The Nrf2-antioxidant pathway was also unaffected by the absence of NLRP3. Furthermore, NLRP3-deficiency prevented the drop in autophagy and mice showed less mitochondrial damage than wild-type animals. Interestingly, melatonin treatment recovered mitochondrial dynamics altered by aging and had few effects on cardiac autophagy. Melatonin supplementation also had an anti-apoptotic action in addition to restoring Nrf2-antioxidant capacity and improving mitochondria ultrastructure altered by aging.
RESUMO
The role of retinoid acid receptor-related orphan receptor alpha (RORα) on male reproductive functions during aging is unclear. Here, we analyze the morphological changes in the testis of both young and aged RORα-deficient mice, with and without melatonin supplementation. Young mutants showed vacuolation, degeneration and pyknosis of spermatogenic epithelium and Sertoli cells. Aged mutants showed atrophy of the seminiferous tubules and absence of mitotic spermatogenic cells. Absence of sperms in many tubules, loss of acrosomal cap, vacuolation and hypertrophy of Sertoli cells were detected in aged mice, with a significant reduction in the number of seminiferous tubules and a significant increase in the number of Leydig cells and telocytes. Repair in seminiferous tubules and interstitial tissues with enhancement of spermatogenesis was observed in melatonin-treated aged mice. Young mutants overexpressed VEGF that was weaker in aged animals and observed only in the spermatocytes, while melatonin increased VEGF expression in spermatocytes and spermatids. Caspase 3 increased in both young and aged mutant mice in all seminiferous tubules and interstitium; caspase 3 immunostaining in seminiferous tubules, however, showed a normal pattern of apoptosis with melatonin supplementation. The present study reports that age-dependent testicular changes in RORα mutant mice were recovered by melatonin treatment.
Assuntos
Envelhecimento/efeitos dos fármacos , Melatonina/farmacologia , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Suplementos Nutricionais , Masculino , Melatonina/administração & dosagem , Camundongos , Testículo/química , Testículo/patologiaRESUMO
To investigate the role of NLRP3 inflammasome in muscular aging, we evaluated here the morphological and functional markers of sarcopenia in the NLRP3-knockout mice, as well as the beneficial effect of melatonin supplementation. The gastrocnemius muscles of young (3 months), early-aged (12 months), and old-aged (24 months) NLRP3-knockout female mice were examined. Moreover, locomotor activity and apoptosis were assessed. The results revealed early markers of sarcopenia at the age of 12 months, including reduction of lactate, ratio of muscle weight to body weight, muscle fibers number, and mitochondrial number. Increased interstitial tissues, apoptosis, and muscle fibers area, as well as mitochondrial damage were detected, with little muscular activity effects. In the old-aged, these alterations progressed with a reduction in locomotor activity, mitochondrial cristae destruction, nuclear fragmentation, tubular aggregates (TAs) formation, and increased frailty index. Oral melatonin supplementation preserved the normal muscular structure, muscle fibers number, and muscular activity in old age. Melatonin enhanced lactate production, recovered mitochondria, inhibited TAs formation, reduced apoptosis, and normalized frailty index. The fewer sarcopenic changes as well as the highly detectable prophylactic effects of melatonin treatment reported here in the muscle of NLRP3-knockout mice comparing with that previously detected in wild-type mice, confirming NLRP3 inflammasome implication in muscular aging and sarcopenia onset and progression.
Assuntos
Envelhecimento/genética , Inflamassomos/genética , Melatonina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Sarcopenia/genética , Envelhecimento/fisiologia , Animais , Biópsia por Agulha , Feminino , Regulação da Expressão Gênica , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Força Muscular/genética , Força Muscular/fisiologia , Sarcopenia/patologia , Sensibilidade e EspecificidadeRESUMO
Resistant hypertension prevalence is progressively increasing, and prolonged exposure to suboptimal blood pressure control results in higher cardiovascular risk and end-organ damage. Among various antihypertensive agents, spironolactone seems the most effective choice to treat resistant hypertension once triple therapy including a diuretic fails. However success in blood pressure control is not guaranteed, adverse effects are not negligible, and no clinical tools are available to predict patient's response. Complementary to our previous study of resistant hypertension metabolism, here we investigated urinary proteome changes with potential capacity to predict response to spironolactone. Twenty-nine resistant hypertensives were included. A prospective study was conducted and basal urine was collected before spironolactone administration. Patients were classified in responders or nonresponders in terms of blood pressure control. Protein quantitation was performed by liquid chromatography-mass spectrometry; ELISA and target mass spectrometry analysis were performed for confirmation. Among 3310 identified proteins, HP (haptoglobin) and HPR (haptoglobin-related protein) showed the most significant variations, with increased levels in nonresponders compared with responders before drug administration (variation rate, 5.98 and 7.83, respectively). Protein-coordinated responses were also evaluated by functional enrichment analysis, finding oxidative stress, chronic inflammatory response, blood coagulation, complement activation, and regulation of focal adhesions as physiopathological mechanisms in resistant hypertension. In conclusion, protein changes able to predict patients' response to spironolactone in basal urine were here identified for the first time. These data, once further confirmed, will support clinical decisions on patients' management while contributing to optimize the rate of control of resistant hypertensives with spironolactone.
Assuntos
Antígenos de Neoplasias/urina , Pressão Sanguínea/efeitos dos fármacos , Resistência a Medicamentos , Haptoglobinas/urina , Hipertensão/tratamento farmacológico , Espironolactona/uso terapêutico , Idoso , Biomarcadores/urina , Feminino , Humanos , Hipertensão/fisiopatologia , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND AIMS: Cell therapy with mesenchymal stromal cells (MSCs) offers new hope for patients suffering from spinal cord injury (SCI). METHODS: Ten patients with established incomplete SCI received four subarachnoid administrations of 30 × 106 autologous bone marrow MSCs, supported in autologous plasma, at months 1, 4, 7 and 10 of the study, and were followed until the month 12. Urodynamic, neurophysiological and neuroimaging studies were performed at months 6 and 12, and compared with basal studies. RESULTS: Variable improvement was found in the patients of the series. All of them showed some degree of improvement in sensitivity and motor function. Sexual function improved in two of the eight male patients. Neuropathic pain was present in four patients before treatment; it disappeared in two of them and decreased in another. Clear improvement in bladder and bowel control were found in all patients suffering previous dysfunction. Before treatment, seven patients suffered spasms, and two improved. Before cell therapy, nine patients suffered variable degree of spasticity, and 3 of them showed clear decrease at the end of follow-up. At this time, nine patients showed infra-lesional electromyographic recordings suggesting active muscle reinnervation, and eight patients showed improvement in bladder compliance. After three administrations of MSCs, mean values of brain-derived neurotrophic factor, glial-derived neurotrophic factor, ciliary neurotrophic factor, and neurotrophin 3 and 4 showed slight increases compared with basal levels, but without statistically significant difference. CONCLUSIONS: Administration of repeated doses of MSCs by subarachnoid route is a well-tolerated procedure that is able to achieve progressive and significant improvement in the quality of life of patients suffering incomplete SCI.
Assuntos
Transfusão de Sangue Autóloga/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Qualidade de Vida , Traumatismos da Medula Espinal/terapia , Adulto , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plasma , Traumatismos da Medula Espinal/patologia , Espaço Subaracnóideo , Transplante AutólogoRESUMO
BACKGROUND: The Stevia rebaudiana plant is likely to become a major source of high-potency sweetener for the growing natural-food market. S. rebaudiana is the source of a number of sweet diterpenoid glycosides, but the major sweet constituents are rebaudioside A and stevioside. These two constituents have similar pharmacokinetic and metabolic profiles in rats and humans, and thus, studies carried out with either steviol glycoside are relevant to both. Other studies illustrate the diversity of voluntary sweet intake in mammals. METHOD: This study was done using a series of two-bottle tests that compared a wide range of sweetener concentrations versus saccharin concentrations and versus water. RESULTS: Wistar rats displayed preferences for stevia extract and pure rebaudioside A solutions over water at a range of concentrations (0.001% to 0.3%), and their intake peak occurred at 0.1% concentration. They also preferred solutions prepared with a commercial rebaudioside A plus erythritol mixture to water, and their peak was at 2% concentration. CONCLUSIONS: The present study provides new information about the responses of Wistar rats to stevia compounds and commercial stevia products such as Truvia. These results could help with the appropriate dosage selection for focused behavioral and physiological studies on stevia
ANTECEDENTES: la planta Stevia rebaudiana se convertirá en una de las principales fuentes de edulcorantes debido al crecimiento del consumo de productos naturales en el mercado. S. rebaudiana contiene distintos glucósidos diterpenoides, pero los que proporcionan dulzor son el rebaudiosido A y el esteviosido. Estos dos compuestos tienen perfiles farmacocinéticos y metabólicos similares en ratas y humanos. Por otro lado, hay estudios que muestran la existencia de distintos patrones de ingesta voluntaria de edulcorantes en los mamíferos. MÉTODO: se realizaron series de la prueba de libre elección entre dos botellas. Comparamos la ingesta de un rango de concentraciones de edulcorantes frente al agua y frente a sacarina. RESULTADOS: las ratas Wistar prefieren el extracto de estevia y el rebaudiosido A (concentraciones desde 0,001% hasta 0,3%) frente al agua, la ingesta máxima fue a la concentración de 0,1%. También prefieren las soluciones preparadas con el producto comercial Truvia (rebaudiósido A y eritritol) frente al agua, la ingesta máxima fue a la concentración de 2%. CONCLUSIONES: nuestro trabajo proporciona nueva información sobre la preferencia gustativa de las ratas Wistar por distintos compuestos de estevia. Estos resultados ayudarán al diseño de estudios centrados en los efectos comportamentales y fisiológicos del consumo de estevia
Assuntos
Animais , Masculino , Feminino , Ratos , Stevia/fisiologia , Ratos Wistar/psicologia , Glucosídeos/uso terapêutico , Comportamento Animal/fisiologia , Eritritol/metabolismo , Eritritol/farmacologia , Eritritol/uso terapêutico , Edulcorantes/uso terapêutico , Stevia/metabolismo , Psicologia Experimental/instrumentação , Psicologia Experimental/métodos , Psicologia Comparada/métodos , Análise de VariânciaRESUMO
BACKGROUND: The Stevia rebaudiana plant is likely to become a major source of high-potency sweetener for the growing natural-food market. S. rebaudiana is the source of a number of sweet diterpenoid glycosides, but the major sweet constituents are rebaudioside A and stevioside. These two constituents have similar pharmacokinetic and metabolic profiles in rats and humans, and thus, studies carried out with either steviol glycoside are relevant to both. Other studies illustrate the diversity of voluntary sweet intake in mammals. METHOD: This study was done using a series of two-bottle tests that compared a wide range of sweetener concentrations versus saccharin concentrations and versus water. RESULTS: Wistar rats displayed preferences for stevia extract and pure rebaudioside A solutions over water at a range of concentrations (0.001% to 0.3%), and their intake peak occurred at 0.1% concentration. They also preferred solutions prepared with a commercial rebaudioside A plus erythritol mixture to water, and their peak was at 2% concentration. CONCLUSIONS: The present study provides new information about the responses of Wistar rats to stevia compounds and commercial stevia products such as Truvia. These results could help with the appropriate dosage selection for focused behavioral and physiological studies on stevia.
Assuntos
Diterpenos do Tipo Caurano , Preferências Alimentares , Glucosídeos , Edulcorantes , Animais , Diterpenos do Tipo Caurano/administração & dosagem , Feminino , Glucosídeos/administração & dosagem , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Stevia , Edulcorantes/administração & dosagemRESUMO
OBJECTIVE: To investigate the effect of lysophosphatidic acid (LPA) receptor inhibition in a mouse model of autoantibody-mediated arthritis. METHODS: Arthritis was induced in C57BL/6 mice by K/BxN serum transfer. Arthritic mice were treated with the LPA receptor antagonist, Ki16425 and arthritis severity was assessed clinically and histologically. Expression of inflammatory mediators in joints was identified by a mouse cytokine array and validated by western blot and real-time PCR assays. Effects of treatment with LPA receptor antagonist or with small interfering RNA on bone metabolism were assessed by in vitro assays of osteoclastogenesis, bone resorption, osteoblasts differentiation and bone mineralisation. RESULTS: Mice treated with the LPA receptor antagonist Ki16425 showed attenuated arthritis characterised by reduction of synovial inflammation, cartilage damage and, more markedly, bone erosion. We detected increased apoptosis, reduction of inflammatory mediators and of bone remodelling proteins in arthritic joints from mice treated with Ki16425. In addition, we demonstrated that inhibition or suppression of LPA1 receptor reduces osteoclast differentiation and bone resorption and, on the contrary, it promotes differentiation of osteoblasts and bone mineralisation. CONCLUSIONS: Pharmacological inhibition of LPA1 receptor in the K/BxN serum-transfer arthritis model led to reduction of severity of arthritis involving multiple mechanisms, increased apoptosis, reduced inflammatory mediators and proteins involved in bone remodelling, that show LPA1 as a very promising target in rheumatoid arthritis treatment.
Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Isoxazóis/farmacologia , Propionatos/farmacologia , Receptores de Ácidos Lisofosfatídicos/antagonistas & inibidores , Sinovite/tratamento farmacológico , Animais , Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Sinovite/imunologiaRESUMO
PURPOSE: International organizations such as National Comprehensive Cancer Network and NICE recommend implementation of routine screening programs for detecting and managing psychosocial distress among cancer patients. The selection of an adequate screening tool is crucial to the effectiveness of these programs. The present study examines the emotional symptomatology captured by the Distress Thermometer (DT) and its accuracy and validity as a screening tool in cancer. It also explores the possible discrepancy between patient distress and the use of psycho-oncology resources. METHODS: A heterogeneous sample of 962 adult cancer patients completed the DT, the Problem List (PL), the Brief Symptom Inventory-18 (BSI-18), and the Psychosocial Questionnaire. RESULTS: The DT was significantly correlated with BSI-18 symptoms and the emotional problems listed on the PL. Receiver Operating Characteristic analysis showed good diagnostic accuracy for the DT (area under the curve = .82, 95 %CI [.79-.85]). For a selected DT cutoff of 5, standard measures (sensitivity = 90 %, specificity = 64 %, predictive positive value = 35 %, and negative predictive value = 97 %) and Clinical Utility Indexes (utility index negative = .62 and utility index positive = .32) indicated that the DT was adequate for "screening" while it was limited for "case finding." Finally, 81.30 % of patients with clinical distress had not sought or were not receiving professional psychosocial support at the time of the study. CONCLUSION: The DT is appropriate for use as a rapid screening instrument for cancer patients in a Spanish population because it assesses a broad concept of distress including both anxiety and depression symptoms. The diagnostic accuracy of the DT could be improved with minor proposed modifications to the DT and the inclusion of nonemotional ultrashort measures.
Assuntos
Sintomas Afetivos/diagnóstico , Neoplasias/psicologia , Psicometria/normas , Estresse Psicológico/diagnóstico , Inquéritos e Questionários/normas , Adulto , Sintomas Afetivos/etiologia , Sintomas Afetivos/psicologia , Idoso , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/psicologia , Aconselhamento/estatística & dados numéricos , Depressão/diagnóstico , Depressão/etiologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/terapia , Psicometria/métodos , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espanha , Estresse Psicológico/etiologia , Estresse Psicológico/psicologiaRESUMO
BACKGROUND: Although hypercaloric interventions are associated with nutritional, endocrine, metabolic, and cardiovascular disorders in obesity experiments, a rational distinction between the effects of excess adiposity and the individual roles of dietary macronutrients in relation to these disturbances has not previously been studied. This investigation analyzed the correlation between ingested macronutrients (including sucrose and saturated and unsaturated fatty acids) plus body adiposity and metabolic, hormonal, and cardiovascular effects in rats with diet-induced obesity. METHODS: Normotensive Wistar-Kyoto rats were submitted to Control (CD; 3.2 Kcal/g) and Hypercaloric (HD; 4.6 Kcal/g) diets for 20 weeks followed by nutritional evaluation involving body weight and adiposity measurement. Metabolic and hormonal parameters included glycemia, insulin, insulin resistance, and leptin. Cardiovascular analysis included systolic blood pressure profile, echocardiography, morphometric study of myocardial morphology, and myosin heavy chain (MHC) protein expression. Canonical correlation analysis was used to evaluate the relationships between dietary macronutrients plus adiposity and metabolic, hormonal, and cardiovascular parameters. RESULTS: Although final group body weights did not differ, HD presented higher adiposity than CD. Diet induced hyperglycemia while insulin and leptin levels remained unchanged. In a cardiovascular context, systolic blood pressure increased with time only in HD. Additionally, in vivo echocardiography revealed cardiac hypertrophy and improved systolic performance in HD compared to CD; and while cardiomyocyte size was unchanged by diet, nuclear volume and collagen interstitial fraction both increased in HD. Also HD exhibited higher relative ß-MHC content and ß/α-MHC ratio than their Control counterparts. Importantly, body adiposity was weakly associated with cardiovascular effects, as saturated fatty acid intake was directly associated with most cardiac remodeling measurements while unsaturated lipid consumption was inversely correlated with these effects. CONCLUSION: Hypercaloric diet was associated with glycemic metabolism and systolic blood pressure disorders and cardiac remodeling. These effects directly and inversely correlated with saturated and unsaturated lipid consumption, respectively.