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1.
Toxics ; 10(9)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36136478

RESUMO

Perinatal exposure to bisphenol A (BPA) in murine models has been reported to affect social behavior and increase anxiety. However, there is little information about the effects of BPA exposure during puberty, a period in which sex hormones influence the maturation and differentiation of the brain. In this work, we evaluated the effect of BPA administration during the juvenile stage (PND 21-50) on anxiety in male and female rats. Newly weaned Wistar rats were treated with BPA (0, 50, or 500 µg/kg/day) for 30 days. To compare the intra- and inter-sex behavioral profiles, rats were evaluated using four different anxiety models: the Open field test (OFT), the Elevated plus maze (EPM), the Light-dark box test (LDBT), and the Defensive burying test (DBT). Males exhibited a clear-cut anxious profile at both doses in all four tests, while no clear behavioral effect of BPA exposure was observed in female rats. The latter showed an altered estrous cycle that initiated earlier in life and had a shorter duration, with the estrous phase predominating. Moreover, the expression of ESR1, ESR2, GABRA1, GRIN1, GR, MR, and AR genes increased in the hippocampus and hypothalamus of male rats treated with 50 µg/kg, but not in females. Our results indicate that BPA consistently induces a higher anxiety profile in male than in female rats, as evidenced predominantly by an increase in passive-coping behaviors and changes in brain gene expression, highlighting the importance of sex in peripubertal behavioral toxicology studies.

2.
Endocrinol Diabetes Nutr (Engl Ed) ; 69(3): 168-177, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35396115

RESUMO

BACKGROUND: The consumption of artificially sweetened beverages (ASBs) has been linked to metabolic alterations. The effect of reducing the regular consumption of these beverages on the metabolism is currently unknown. OBJECTIVE: To evaluate the effect of reducing consumption of ASBs on the metabolism in overweight young adults. DESIGN: A randomised, single-blind, controlled, 12-week, clinical trial was performed in overweight young adults who regularly consume ASBs. The 45 subjects who participated in the study were randomly divided into two groups: (1) control group (n=21) and (2) intervention group (no intake of ASBs, n=24). Body weight and composition, fasting plasma concentrations of glucose, triglycerides, insulin, cholesterol, low-density lipoproteins and high-density lipoproteins were measured at the beginning and end of the study. and the HOMA-IR was calculated. RESULTS: At the end of 12 weeks, the intervention group showed a significant decrease (as opposed to an increase in the control group) in the percentage of change in body weight (-1.22% vs 1.31%, p<0.004), body fat (-6.28% vs 6.15%, p<0.001) and insulin resistance index (-12.06 vs 38.21%, p<0.00002), as well as in levels of glucose (-4.26% vs 0.51%, p<0.05), triglycerides (-14.74% vs 19.90%, p<0.006), insulin (-8.02% vs 39.23%, p<0.00005), cholesterol (-8.71% vs 0.77%, p<0.01) and LDL (-9.46% vs 9.92%, p<0.004). CONCLUSION: A reduction in habitual consumption of ASBs in overweight young adults decreases biochemical measurements, body weight and composition, suggesting a participation in the metabolic processes.


Assuntos
Sobrepeso , Edulcorantes , Bebidas Adoçadas Artificialmente , Peso Corporal , Fatores de Risco Cardiometabólico , Colesterol , Glucose , Humanos , Insulina , Método Simples-Cego , Edulcorantes/efeitos adversos , Triglicerídeos , Adulto Jovem
4.
Cir Esp (Engl Ed) ; 99(9): 635-647, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34690075

RESUMO

INTRODUCTION: Bariatric surgery is a relatively safe surgical procedure with a high success rate. However, recent reports indicate a higher prevalence of alcohol or substance abuse disorder in this patient group. The purpose of this study was to review the related evidence to serve as a reference for multidisciplinary teams who treat these patients. METHODS: We searched the PubMed and CENTRAL databases. The odds ratios were extracted from the different articles, comparing the prevalence of the abuse of alcohol or other substances in the postoperative period versus preoperative levels. We also compared the prevalence of alcohol use disorder after different types of bariatric surgery. RESULTS: A total of 49 121 bariatric patients (80.8% female) were evaluated for alcohol use disorder. In general, bariatric surgery was found to be associated with an increase in the prevalence of alcohol abuse (4.58 ± 5.3 vs. 1.58 ± 10.7% in the preoperative period). We also found that the population of patients who underwent RYGB procedures had a higher prevalence of alcohol use disorder than patients who underwent another type of surgery (OR: 1.83; 95% CI: 1.51-2.21). The prevalence of substance abuse disorder (other than alcohol) after this procedure is less studied, although there appears to be an increased risk of abuse of certain substances. CONCLUSIONS: Bariatric surgery is the best treatment for obesity and its complications. The evidence reviewed suggests that it correlates with a modest but consistent increase in the prevalence of abuse of alcohol and other substances. Medical teams who treat bariatric patients must be informed about this eventuality for its timely prevention, diagnosis and treatment.


Assuntos
Alcoolismo , Cirurgia Bariátrica , Transtornos Relacionados ao Uso de Substâncias , Alcoolismo/epidemiologia , Cirurgia Bariátrica/efeitos adversos , Etanol , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
5.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34274304

RESUMO

BACKGROUND: The consumption of artificially sweetened beverages (ASBs) has been linked to metabolic alterations. The effect of reducing the regular consumption of these beverages on the metabolism is currently unknown. OBJECTIVE: To evaluate the effect of reducing consumption of ASBs on the metabolism in overweight young adults. DESIGN: A randomised, single-blind, controlled, 12-week, clinical trial was performed in overweight young adults who regularly consume ASBs. The 45 subjects who participated in the study were randomly divided into two groups: (1) control group (n=21) and (2) intervention group (no intake of ASBs, n=24). Body weight and composition, fasting plasma concentrations of glucose, triglycerides, insulin, cholesterol, low-density lipoproteins and high-density lipoproteins were measured at the beginning and end of the study. and the HOMA-IR was calculated. RESULTS: At the end of 12 weeks, the intervention group showed a significant decrease (as opposed to an increase in the control group) in the percentage of change in body weight (-1.22% vs 1.31%, p<0.004), body fat (-6.28% vs 6.15%, p<0.001) and insulin resistance index (-12.06 vs 38.21%, p<0.00002), as well as in levels of glucose (-4.26% vs 0.51%, p<0.05), triglycerides (-14.74% vs 19.90%, p<0.006), insulin (-8.02% vs 39.23%, p<0.00005), cholesterol (-8.71% vs 0.77%, p<0.01) and LDL (-9.46% vs 9.92%, p<0.004). CONCLUSION: A reduction in habitual consumption of ASBs in overweight young adults decreases biochemical measurements, body weight and composition, suggesting a participation in the metabolic processes.

7.
Front Neurosci ; 15: 579263, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790729

RESUMO

Hepatic encephalopathy (HE) is one of the most disabling metabolic diseases. It consists of a complication of liver disease through the action of neurotoxins, such as excessive production of ammonia from liver, resulting in impaired brain function. Its prevalence and incidence are not well known, although it has been established that up to 40% of cirrhotic patients may develop HE. Patients with HE episodes display a wide range of neurological disturbances, from subclinical alterations to coma. Recent evidence suggests that the resolution of hepatic encephalopathy does not fully restore cognitive functioning in cirrhotic patients. Therefore, the aim of this review was to evaluate the evidence supporting the presence of lingering cognitive deficits in patients with a history of HE compared to patients without HE history and how liver transplant affects such outcome in these patients. We performed two distinct meta-analysis of continuous outcomes. In both cases the results were pooled using random-effects models. Our results indicate that cirrhotic patients with a history of HE show clear cognitive deficits compared control cirrhotic patients (Std. Mean Difference (in SDs) = -0.72 [CI 95%: -0.94, -0.50]) and that these differences are not fully restored after liver transplant (Std. Mean Difference (in SDs) = -0.72 [CI 95%: -0.94, -0.50]).

8.
Med Chem ; 17(6): 587-600, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31995016

RESUMO

BACKGROUND: Cervical cancer is a major public health issue worldwide, occurring in the vast majority of cases (85%) in low-income countries. Human papillomavirus (HPV) mainly infects the mucosal epithelium, and a small portion causes over 600,000 cases every year worldwide at various anatomical spots, mainly leading to anogenital and head and neck. INTRODUCTION: The E6 oncoprotein encoded by cancer-associated alpha HPV can transform epithelial cells into tumorigenic tissue. Therapy for this infection and blocking of the HPV E6 oncoprotein could be provided with cost-effective and abundant natural products which are an exponentially growing topic in the literature. Finding an active natural compound that readily blocks HPV E6 oncoprotein which could be available for developing countries without expensive extraction processes or costly synthetic pathways is of major interest. METHODS: Molecular dynamics simulation was performed using the most up-to-date AMBER protein force field ff14SB and a GPU enabled high performance computing cluster. RESULTS: In this research, we present a study of the binding properties between 10 selected natural compounds that are readily available with two variants of the E6 oncoprotein types (HPV-16 and HPV-18) using 10+ microsecond molecular dynamics simulations. CONCLUSION: Our results suggest that crocetin, ergosterol peroxide and κ-carrageenan natural products bind strongly to both HPV-16 and HPV-18 and could potentially serve as a scaffolding for further drug development.


Assuntos
Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Proteínas de Ligação a DNA/metabolismo , Simulação de Dinâmica Molecular , Proteínas Oncogênicas Virais/metabolismo , Proteínas Repressoras/metabolismo , Proteínas de Ligação a DNA/química , Proteínas Oncogênicas Virais/química , Ligação Proteica , Conformação Proteica , Proteínas Repressoras/química , Risco
9.
Int J Med Mushrooms ; 22(11): 1109-1119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33426842

RESUMO

Every year, more than 500,000 new cases of cervical cancer are reported, making it the fourth leading cause of cancer globally. Although human papillomavirus (HPV) vaccines show promise as a protective measure, HPV-related cancers remain a public health problem since the vaccines, which are only specific to certain viral types, are unavailable for mass distribution. Furthermore, the effects of toxicity following ionizing radiation therapy have reoriented views toward the search for radiosensitizers that can reduce toxicity as a consequence of decreased radiation doses. Here, we isolated ergosterol peroxide (EP) from Pleurotus ostreatus and purified it to test its potential effects in vitro. We thus observed that a gradual increase in EP dose correlates with a loss of viability in HeLa and CaSki cervical cell lines. Dose/response curves were constructed using cervical cancer cell lines, as well as normal human peripheral blood mononuclear cells. The selectivity of EP in human lymphocytes and cervical cancer cell lines was tested, and no toxicity was found in normal cells. A combination of treatments revealed a radiosensitizer effect in HeLa cells, when measuring the exposure to EP followed by irradiation with 137Cs. Our findings suggest that EP may be effective as a radiosensitizer in treating cervical cancer.


Assuntos
Ergosterol/análogos & derivados , Extratos Vegetais/farmacologia , Pleurotus/química , Radiossensibilizantes/farmacologia , Neoplasias do Colo do Útero/radioterapia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ergosterol/farmacologia , Feminino , Humanos , Tolerância a Radiação , Neoplasias do Colo do Útero/fisiopatologia
10.
Molecules ; 24(21)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671813

RESUMO

Plant-derived compounds have recently attracted greater interest in the field of new therapeutic agent development. These compounds have been widely screened for their pharmacological effects. Polyphenols, such as soy-derived isoflavones, also called phytoestrogens, have been extensively studied due to their ability to inhibit carcinogenesis. These compounds are chemically similar to 17ß-estradiol, and mimic the binding of estrogens to its receptors, exerting estrogenic effects in target organs. Genistein is an isoflavone derived from soy-rich products and accounts for about 60% of total isoflavones found in soybeans. Genistein has been reported to exhibit several biological effects, such as anti-tumor activity (inhibition of cell proliferation, regulation of the cell cycle, induction of apoptosis), improvement of glucose metabolism, impairment of angiogenesis in both hormone-related and hormone-unrelated cancer cells, reduction of peri-menopausal and postmenopausal hot flashes, and modulation of antioxidant effects. Additionally, epidemiological and clinical studies have reported health benefits of genistein in many chronic diseases, such as cardiovascular disease, diabetes, and osteoporosis, and aid in the amelioration of typical menopausal symptoms, such as anxiety and depression. Although the biological effects are promising, certain limitations, such as low bioavailability, biological estrogenic activity, and effects on target organs, have limited the clinical applications of genistein to some extent. Moreover, studies report that modification of its molecular structure may eliminate the biological estrogenic activity and its effects on target organs. In this review, we summarize the potential benefits of genistein on menopause symptoms and menopause-related diseases like cardiovascular, osteoporosis, obesity, diabetes, anxiety, depression, and breast cancer.


Assuntos
Genisteína/farmacologia , Menopausa/efeitos dos fármacos , Antidepressivos/farmacologia , Cardiotônicos/farmacologia , Feminino , Genisteína/química , Humanos , Sistema Vasomotor/efeitos dos fármacos
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