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1.
Cureus ; 16(2): e54289, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38496112

RESUMO

Munchausen Syndrome (MS) has been widely recognized as a severe manifestation of factitious disorder, a condition where individuals intentionally fabricate or exaggerate symptoms for psychological gratification. It represents a complex diagnostic challenge due to its elusive nature and intricate relationship with various medical conditions. We present a clinical case of a 44-year-old woman observed in the context of Liaison Psychiatry, demonstrating the intricate interplay between chronic medical conditions, psychiatric factors, and the challenges in diagnosing and managing MS. The patient exhibited a history of recurrent hospitalizations, difficult-to-heal injuries, and a pronounced preference for surgical interventions. Despite diagnostic difficulties and poor therapeutic adherence, a multidisciplinary team approach involving plastic surgery, orthopedics, physical medicine, and rehabilitation, alongside Liaison Psychiatry, led to the diagnosis of MS with chronic osteomyelitis, ultimately necessitating a transtibial amputation. The case underscores the importance of early detection, a multidisciplinary approach, and the role of Liaison Psychiatry in managing MS. While early diagnosis may not alter the disease course, it can prevent unnecessary interventions and mitigate associated risks. The case also highlights the need for continuous psychiatric support and family involvement in addressing the recurrence of self-injurious behaviors. Further research is essential to enhance our understanding and develop effective treatment strategies for MS, contributing to improved diagnostic precision and overall management of this challenging psychiatric disorder.

2.
J Clin Sleep Med ; 20(4): 653-656, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38152859

RESUMO

Bleeding tongue-biting episodes during sleep are a rare and alarming situation that can negatively impact the child's and parents' sleep, affecting their quality of life. Although highly suggestive of epilepsy, a differential diagnosis should be made with sleep-related movement disorders such as bruxism, hypnic myoclonus, facio-mandibular myoclonus, and geniospasm when this hypothesis is excluded. The clinical history, electroencephalogram, and video-polysomnography are essential for diagnostic assessment. Treatment with clonazepam can be necessary in the presence of frequent tongue biting that causes severe injuries and sleep disturbance. This study reports the challenging case of managing and diagnosing a 2-year-old boy with recurrent tongue biting during sleep since he was 12 months old, causing bleeding lacerations, frequent awakenings, and significant sleep impairment with daytime consequences for him and his family. CITATION: Cascais I, Ashworth J, Ribeiro L, Freitas J, Rios M. A rare case of tongue biting during sleep in childhood. J Clin Sleep Med. 2024;20(4):653-656.


Assuntos
Mioclonia , Masculino , Criança , Humanos , Pré-Escolar , Lactente , Mioclonia/tratamento farmacológico , Qualidade de Vida , Sono , Língua , Clonazepam/uso terapêutico
3.
Vaccines (Basel) ; 11(3)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36992287

RESUMO

BACKGROUND: Patients with immune-mediated inflammatory diseases (IMIDs) treated with immunomodulatory therapy present an increased susceptibility to infections. Vaccination is a crucial element in the management of IMID patients; however, rates remain suboptimal. This study intended to clarify the adherence to prescribed vaccines. MATERIALS AND METHODS: This prospective cohort study included 262 consecutive adults with inflammatory bowel disease and rheumatological diseases who underwent an infectious diseases evaluation before initiating or switching immunosuppressive/biological therapy. Vaccine prescription and adherence were assessed during an infectious diseases (ID) consultation using a real-world multidisciplinary clinical project. RESULTS: At baseline, less than 5% had all their vaccines up-to-date. More than 650 vaccines were prescribed to 250 (95.4%) patients. The most prescribed were pneumococcal and influenza vaccines, followed by hepatitis A and B vaccines. Adherence to each of the vaccines ranged from 69.1-87.3%. Complete adherence to vaccines occurred in 151 (60.4%) patients, while 190 (76%) got at least two-thirds of them. Twenty patients (8%) did not adhere to any of the vaccines. No significant differences were found in the adherence rates of patients with different sociodemographic and health-related determinants. CONCLUSIONS: ID physicians can play a role in the process of increasing vaccine prescription and adherence. However, more data on patients' beliefs and vaccine hesitancy, along with mobilization of all health care professionals and adequate local interventions, shall be considered to improve vaccine adherence.

4.
Acta Med Port ; 35(6): 494-503, 2022 Jun 01.
Artigo em Português | MEDLINE | ID: mdl-36279519

RESUMO

Q fever (or query fever) is a zoonotic infectious disease with worldwide distribution transmitted by an intracellular Gram-negative bacterium, Coxiella burnetii. The most common identified sources of human infection are farm animals, such as sheep, goats and cattle. The disease is endemic in mainland Portugal, with most cases notified in the central and southern regions. Q fever is a complex and pleomorphic disease, with those affected presenting with a wide range of manifestations from acute self-limited flu-like symptoms with good prognosis to persistent localized forms that may harbor a poor prognosis. Cases might occur in an isolated fashion or following outbreaks with great public health repercussion, as seen recently in the Netherlands from 2007 to 2010. Given the complexity of this infection, there is no universal consensus to date on the best strategy to manage Q fever patients. These guidelines provide recommendations regarding the treatment and follow-up of these patients, based on studies, on the author's experience and on the opinion of international experts. The aim is to harmonize the management of these patients taking into account not only the clinical manifestations but also the risk factors of the host in order to reduce disease-associated morbidity and mortality.


A febre Q (do inglês query fever) é uma zoonose de distribuição mundial transmitida por uma bactéria intracelular Gram negativo, Coxiella burnetii. Os ruminantes domésticos são os principais reservatórios implicados na transmissão da doença ao ser humano. Em Portugal continental, esta doença é endémica, com o maior número de casos notificados nas regiões Centro e Sul. A doença causada por C. burnetii é complexa e polimórfica, podendo manifestar-se sob uma forma aguda autolimitada do tipo gripal, com um curso ligeiro a moderado e prognóstico benigno, e/ou sob uma forma persistente, geralmente localizada e de evolução grave ou potencialmente fatal. Pode ocorrer em casos isolados ou em contexto de surtos, alguns com importantes implicações em saúde pública, como o verificado na Holanda em 2007 - 2010. Dada a complexidade e espetro clínico da febre Q, não existe um consenso universal sobre a melhor forma de tratamento, gestão e seguimento destes doentes. Este protocolo é uma sugestão de tratamento e seguimento dos doentes com febre Q, compilando a informação de estudos e opiniões de peritos internacionais e a experiência dos autores. Pretende-se assim uniformizar a gestão destes doentes tendo em conta não só o espetro das suas manifestações clínicas, mas também os fatores de risco do hospedeiro, por forma a reduzir morbimortalidade que a doença possa causar.


Assuntos
Coxiella burnetii , Febre Q , Doenças dos Ovinos , Humanos , Ovinos , Bovinos , Animais , Febre Q/diagnóstico , Febre Q/terapia , Febre Q/epidemiologia , Seguimentos , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/microbiologia , Cabras
5.
Int J Obes (Lond) ; 46(11): 2006-2012, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35987956

RESUMO

BACKGROUND/OBJECTIVE: There is evidence that metabolic profile changes after Roux-Y gastric bypass (RYGB), especially due to modifications in the gastrointestinal tract. In addition, previous studies have suggested that probiotics can modify the microbiome and produce metabolites important for metabolic health maintenance. In this sense, the aim of this study was to verify the influence of probiotic supplementation on the plasma metabolite profile after RYGB. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial conducted with 31 patients subjected to RYGB surgery, randomized in probiotic group that was supplemented with a probiotic supplement (FloraVantage®) for 3 months after surgery or a placebo group. Plasma metabonomics was performed using nuclear magnetic resonance (NMR) at the preoperative period (T0) and at 45-50 days (T1) and 90-95 days (T2) during the postoperative period/intervention. RESULTS: Reductions in trimethylamine-N-oxide (TMAO) and alanine were observed in both groups, however this reduction was greater in the probiotic group (TMAO 13.82%, p = 0.01 and alanine 14.03%, p = 0.03) at T2. Additionally, ß-hydroxybutyrate (BHB) levels increased 10.77% in the probiotic group (p = 0.03) compared to the placebo group at T2. CONCLUSION: Supplementation with Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 was able to associate with significant differences in relevant plasma metabolites associated with improved metabolic health.


Assuntos
Derivação Gástrica , Probióticos , Humanos , Ácido 3-Hidroxibutírico , Estudos Prospectivos , Glicemia/metabolismo , Probióticos/uso terapêutico , Suplementos Nutricionais , Método Duplo-Cego , Alanina , Óxidos
6.
Front Psychol ; 12: 660650, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867573

RESUMO

There is evidence for the positive impact of mindfulness in children. However, little is known about the techniques through which mindfulness practice results in differential outcomes. Therefore, this study intended to systematically review the available evidence about the efficacy of meditation techniques used by mindfulness-based programs on cognitive, socio-emotional, and academic skills of children from 6 to 12 years of age. The review was registered on the PROSPERO database, and the literature search was conducted according to PICO criteria and PRISMA guidelines. The EBSCO databases were searched, and 29 studies were eligible: nine randomized controlled trials and 20 quasi-experimental studies. All the included randomized controlled trials were rated as having a high risk of bias. Overall, the evidence for mindfulness techniques improving cognitive and socio-emotional skills was reasonably strong. Specifically, for cognitive skills, results showed that all the interventions used "body-centered meditations" and "mindful observations." Regarding socio-emotional skills, although all the studies applied "body-centered meditations" and "mindful observations," "affect-centered meditations" were also frequent. For academic skills, just one quasi-experimental trial found improvements, thus making it difficult to draw conclusions. Further research is crucial to evaluate the unique effects of different meditation techniques on the cognitive, social-emotional, and academic skills of children. Systematic Review Registration: Identifier: RD42019126767.

10.
Mol Biol Rep ; 48(9): 6401-6411, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34403036

RESUMO

BACKGROUND: Obesity is considered a chronic inflammatory disease and transforming growth factor beta 1 (TGFß1) might exert important roles in disease pathogenesis regulating adipocyte differentiation and immune-inflammatory environment. However, the role of this cytokine as a biomarker in obesity is poorly addressed. Therefore, the present study aimed to evaluate the impact of TGFB1 polymorphisms and TGFß1 plasmatic levels in obesity METHODS AND RESULTS: TGFB1 promoter region polymorphisms (rs1800468, G-800A and rs1800469, C-509 T) were evaluated in 75 obese patients and 45 eutrophic patients through PCR-RFLP and plasmatic TGFß1 was quantified through ELISA from 37 of the obese patients, and correlations with clinical and biochemical parameters were tested. Despite no association was found between TGFB1 polymorphisms and obesity susceptibility, several correlations with clinical data were noted. Among others, AC haplotype negatively correlated with plasmatic TGFß1, while plasmatic TGFß1 negatively correlated with C-reactive protein and positively correlated with liver abnormalities on ultrasound and, specifically, with steatosis presence and degree. Conversely, GT haplotype, which associates with higher TGFß1 production, was also positively correlated with the same parameters of liver abnormalities. Further, plasmatic vitamin D negatively correlated with TGFß1, while positively correlated with AC haplotype. CONCLUSION: Overall, the results indicate that TGFß1 might exert important roles in obesity pathophysiology and correlate with biochemical and clinical parameters both at systemic protein as well as at genetic level. Importantly, the consistent positive correlation at both levels with steatosis might suggest this cytokine as a biomarker for this hepatic abnormality in obese patients.


Assuntos
Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Haplótipos , Obesidade/sangue , Obesidade/complicações , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/genética , Adolescente , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Fígado Gorduroso/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Adulto Jovem
11.
Rev Colomb Psiquiatr (Engl Ed) ; 49(3): 199-201, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32888664

RESUMO

Trazodone is used as an antidepressant in doses between 150 and 600 mg. At lower doses, it is commonly used to treat insomnia. There are few case reports about confusional symptoms as an undesirable side effect of this drug. We report a case of a patient who presented with delirium after prescription of trazodone 100 mg. She required hospitalisation but, shortly after discontinuation of trazodone, the symptoms disappeared without antipsychotic medication. Seven months after the episode, the patient remains asymptomatic.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Delírio/induzido quimicamente , Trazodona/efeitos adversos , Adulto , Antidepressivos de Segunda Geração/administração & dosagem , Feminino , Hospitalização , Humanos , Trazodona/administração & dosagem
12.
Rev. colomb. psiquiatr ; 49(3): 199-201, jul.-set. 2020.
Artigo em Inglês | LILACS, COLNAL | ID: biblio-1149827

RESUMO

ABSTRACT Trazodone is used as an antidepressant in doses between 150 and 600 mg. At lower doses, it is commonly used to treat insomnia. There are few case reports about confusional symptoms as an undesirable side effect of this drug. We report a case of a patient who presented with delirium after prescription of trazodone 100 mg. She required hospitalisation but, shortly after discontinuation of trazodone, the symptoms disappeared without antipsychotic medication. Seven months after the episode, the patient remains asymptomatic.


RESUMEN La trazodona se usa como antidepresivo en dosis de 150-600 mg. En dosis más bajas, se usa comúnmente para tratar el insomnio. Hay pocos reportes de caso sobre síntomas confusionales como un efecto secundario indeseable de este medicamento. Se presenta el caso de una paciente que acudió con delirio después de la prescripción de trazodona 100 mg. La paciente requirió hospitalización pero, poco después de la interrupción de la trazodona, los síntomas desaparecieron sin medicación antipsicótica. A los 7 meses del episodio, la paciente permanecía asintomática.


Assuntos
Humanos , Feminino , Adulto , Trazodona , Delírio , Efeito Rebote , Dosagem , Prescrições , Distúrbios do Início e da Manutenção do Sono , Antidepressivos
13.
Psicosom. psiquiatr ; (12): 35-45, ene.-mar. 2020.
Artigo em Inglês | IBECS | ID: ibc-193132

RESUMO

INTRODUCTION: Fibromyalgia (FM) is a clinical condition characterized by chronic widespread pain, fatigue, non refreshing sleep, mood disturbance and cognitive impairment with accompanying functional disability. It's etiology and even it's existence as a clinical entity have been discussed over the last decades. The lack of understanding of it's physiopathology and the fact that, to this date, there is no strong effective treatment for it makes this discussion even more relevant for clinicians. We here try to revise some of the clinical relevant data available to this day.METHODS: This paper is a narrative revision which gathers information based on a PubMed database search from the last 6 years (2012-2018), in Portuguese or English, for clinical trials or reviews, on the term "Fibromyalgia treatment".Results and discussion: Although there isn't a single strong intervention for FM patients, there is enough evidence suggesting that patient education on the symptoms, on the disease itself and on the realistic treatment goals can benefit these patients. Exercise is also evidence based and should be appropriately suggested. Classical and new Cognitive Behavioural Therapy (CBT) interventions should be seen as the corner stone of treatment in these patients, specially if having co-morbid affective disorders. Many drugs have been studied in the hopes of helping FM patients but few have evidence to support its recommendation


INTRODUCCIÓN: La fibromialgia (FM) es una condición clínica caracterizada por dolor crónico generalizado, fatiga, sueño no reparador, alteraciones del estado de ánimo y deterioro cognitivo con discapacidad asiciada, en casis extremis. Su etiología, e incluso su existencia como entidad clínica, se han debatido en las últimas décadas. La falta de comprensión de su fisiopatología y el hecho de que, hasta la fecha, no exista un tratamiento suficientmente efectivo, convierte el debate en muy relevante para los clínicos. METODOLOGÍA: Este documento revisa información basada en una búsqueda en la base de datos de PubMed de los últimos 6 años (2012-2018), en portugués o inglés, para ensayos clínicos o revisiones, en los términos " Fybromialgia Treatment". Resultados y DISCUSIÓN: Aunque no existe una sola intervención suficientemente sólida para pacientes con FM, gozamos de evidencias suficientes que sugieren que la educación del paciente sobre los síntomas, la enfermedad misma y los objetivos del tratamiento realistas pueden beneficiarlos El ejercicio también se basa en la evidencia debe sugerirse de manera apropiada. Las intervenciones clásicas y de segunda y tercera generación de la Terapia Cognitivo Conductual (TCC) , deben considerarse la piedra angular del tratamiento en estos pacientes, especialmente si se asocian trastornos afectivos comorbidos. Muchos fármacos se han estudiado con la esperanza de ayudar a los pacientes con FM, pero pocos tienen evidencia para sostener su recomendación


Assuntos
Humanos , Fibromialgia/terapia , Prática Clínica Baseada em Evidências/métodos , Dor Crônica/terapia , Transtornos Psicofisiológicos/terapia , Terapia Cognitivo-Comportamental , Educação de Pacientes como Assunto , Exercício Físico , Psicoterapia
14.
J Ment Health ; 29(6): 701-705, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28686478

RESUMO

Background: Medical comorbidity is associated with worse psychiatric outcomes, reduced functioning and higher services use, including inpatient psychiatric care.Aim: We explored the relation between medical comorbidity and length of stay, adjusting for potential confounders.Methods: We retrospectively analyzed an administrative database comprising all inpatient admissions between 2005 and 2014 at the Department of Psychiatry and Mental Health at Vila Nova de Gaia/Espinho Healthcare Center, Vila Nova de Gaia - Portugal. Psychiatric diagnosis and medical comorbidity were coded according to single-level and multi-level classification schemes, respectively, as proposed by the Clinical Classification Software.Results: We included a total of 4613 psychiatric inpatient admissions. The prevalence of medical comorbidity was 25.4% and it was associated with an average increase of 3.5 days (p < 0.001) in length of stay, comparing to patients without medical comorbidity. After adjusting for potential confounders, such as age, sex and year of discharge, medical comorbidity was associated with a 13% increase in length of stay.Conclusions: Medical comorbidity has measurable effects in inpatient outcomes, such as the length of stay and should be a major focus for intervention, in ambulatory care but also during psychiatric hospitalization.


Assuntos
Pacientes Internados , Transtornos Mentais , Comorbidade , Hospitalização , Humanos , Tempo de Internação , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Estudos Retrospectivos
15.
Braz. arch. biol. technol ; 63: e20190395, 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1132237

RESUMO

Abstract The α-tomatine is a steroidal glycoalkaloid found in immature tomatoes (Lycopersicon esculentum) that has important biological functions including the inhibition of cancer cell growth and preventing metastasis. This study aimed to evaluate the effects of α-tomatine on cytotoxicity, cellular proliferation, apoptosis, and mRNA expression of APC, CCNA2, β-catenin, CASP9, BAK, BAX and BCL-XL in colorectal adenocarcinoma cell line HT-29. HT29 cells were treated with three concentrations of α-tomatine (0.1, 1 and 10 µg/mL), although only the 1 µg/mL concentration of α-tomatine was used to evaluate genetic expression patterns by real time-PCR. Results showed that α-tomatine was cytotoxic only at the 10 µg/mL concentration. Cell proliferation was significantly inhibited after the first 24 hours of treatment only with concentrations of 10 µg/mL. In contrast, there were no significant differences in apoptosis for any treatment. In the gene expression studies, only APC expression was significantly altered by α-tomatine treatment. In conclusion, α-tomatine has antiproliferative activity in the first 24h of treatment, does not induce apoptosis in this cell line and causes disruption of cell membranes, thereby increasing the expression of APC gene related to cell cycle.


Assuntos
Tomatina/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , RNA Mensageiro , Neoplasias Colorretais/patologia , Adenocarcinoma/patologia , Expressão Gênica , Células HT29 , Reação em Cadeia da Polimerase em Tempo Real
16.
Cell Physiol Biochem ; 48(1): 397-408, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30016791

RESUMO

BACKGROUND/AIMS: Compared with non-obese individuals, obese individuals commonly store more vitamin D in adipose tissue. VDR expression in adipose tissue can influence adipogenesis and is therefore a target pathway deserving further study. This study aims to assess the role of 1,25(OH)2D3 in human preadipocyte proliferation and differentiation. METHODS: RTCA, MTT, and trypan blue assays were used to assess the effects of 1,25(OH)2D3 on the viability, proliferation, and adipogenic differentiation of SGBS cells. Cell cycle and apoptosis analyses were performed with flow cytometry, triglycerides were quantified, and RT-qPCR was used to assess gene expression. RESULTS: We confirmed that the SGBS cell model is suitable for studying adipogenesis and demonstrated that the differentiation protocol induces cell maturation, thereby increasing the lipid content of cells independently of treatment. 1,25(OH)2D3 treatment had different effects according to the cell stage, indicating different modes of action driving proliferation and differentiation. In preadipocytes, 1,25(OH)2D3 induced G1 growth arrest at both tested concentrations without altering CDKN1A gene expression. Treatment with 100 nM 1,25(OH)2D3 also decreased MTT absorbance and the lipid concentration. Moreover, increased normalized cell index values and decreased metabolic activity were not induced by proliferation or apoptosis. Exposure to 100 nM 1,25(OH)2D3 induced VDR, CEBPA, and CEBPB expression, even in the preadipocyte stage. During adipogenesis, 1,25(OH)2D3 had limited effects on processes such as VDR and PPARG gene expression, but it upregulated CEBPA expression. CONCLUSIONS: We demonstrated for the first time that 1,25(OH)2D3 induces changes in preadipocytes, including VDR expression and growth arrest, and increases the lipid content in adipocytes treated for 16 days. Preadipocytes are important cells in adipose tissue homeostasis, and understanding the role of 1,25(OH)2D3 in adipogenesis is a crucial step in ensuring adequate vitamin D supplementation, especially for obese individuals.


Assuntos
Adipogenia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Vitamina D/análogos & derivados , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Linhagem Celular , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , PPAR gama/genética , PPAR gama/metabolismo , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Regulação para Cima/efeitos dos fármacos , Vitamina D/farmacologia
17.
Biomed Pharmacother ; 91: 861-871, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28501775

RESUMO

Studies have shown that metabolic disorders, serum inflammatory markers and weight gain (obesity) are correlated with vitamin D deficiency. Therefore, the present study correlated the serum calcidiol (s25(OH)D3) levels in a sample of individuals from southern Brazil with variables related to metabolic disorders, obesity and lifestyle habits and assessed the cytotoxic effect of calcitriol on adipose tissue-derived mesenchymal stem cells (ADSCs). The results showed a 79.23% prevalence of hypovitaminosis D in the study population and a correlation (p<0.05) between a low serum vitamin D concentration and an elevated low-density lipoprotein cholesterol (LDL-c) level. Univariate linear regression analysis using 25(OH)D3 as a regressor showed a negative association (p<0.05) with an indoor work environment (ß=-2.305), increased body fat (ß=-0.095), age (ß=-0.065) and high-density lipoprotein cholesterol (HDL-c; ß=-0.109). An in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay performed with ADSCs using five calcitriol concentrations (15.625, 31.25, 62.5, 125 and 250nM) indicated cytotoxic potential (p<0.05) at the 62.5nM concentration at 48 and 72h and at the 125 and 250nM concentrations at 24, 48 and 72h. The results reported herein corroborate one another and suggest a key association between vitamin D deficiency and the development of obesity because ADSCs are involved in adipose tissue hyperplasia and differentiate into adipocytes that can sequester the bioavailable vitamin D necessary for homeostasis.


Assuntos
Tecido Adiposo/citologia , Composição Corporal/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Vitamina D/farmacologia , Adolescente , Adulto , Brasil , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Feminino , Humanos , Concentração Inibidora 50 , Modelos Lineares , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Adulto Jovem
18.
Anticancer Res ; 37(3): 1197-1204, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28314282

RESUMO

Monastrol and its analog oxomonastrol differ by replacement of the sulfur atom present in monastrol to an oxygen atom in oxomonastrol. Monastrol inhibits the mitotic kinesin family member 11 (EG5), which has been studied for its potential use in cancer therapy. The aim of this study was to investigate the effect of monastrol and oxomonastrol on HepG2/C3A cells. Our results showed that monastrol induced DNA damage, reduced cell proliferation, and up-regulated the cytochrome P450 family 1 subfamily A member 1 (CYP1A1) mRNA levels. However, oxomonastrol was cytotoxic only at the highest concentrations used, without reducing cell proliferation and viability. Moreover, no genotoxic damage or alteration of levels of mRNA were found. Our results suggest that monastrol has greater antiproliferative activity compared to oxomonastrol, and this effect is probably related to the DNA damage induced by monastrol and its possible bioactivation demonstrated by the increase in CYP1A1 mRNA expression. Moreover, these effects appear to be related to the presence of the sulfur atom in its structure.


Assuntos
Carcinoma Hepatocelular/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias Hepáticas/metabolismo , Pirimidinas/farmacologia , Pirimidinonas/farmacologia , Tionas/farmacologia , Apoptose , Carcinoma Hepatocelular/patologia , Proliferação de Células , Sobrevivência Celular , Ensaio Cometa , Citocromo P-450 CYP1A1/metabolismo , Dano ao DNA , Regulação Neoplásica da Expressão Gênica , Células Hep G2/efeitos dos fármacos , Humanos , Cinética , Neoplasias Hepáticas/patologia , RNA Mensageiro/metabolismo , Fuso Acromático/efeitos dos fármacos
19.
Phytother Res ; 31(3): 387-394, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27991703

RESUMO

Harpagophytum procumbens (Hp) has been used as antiinflammatory and analgesic agent for the treatment of rheumatic diseases. The principal active component of Hp is harpagoside (HA). We tested the toxicity of this new therapeutic agent in a hepatic cell line (HepG2/C3A). Hp was found to be cytotoxic, and HA was found to decrease the number of cells in S phase, increase the number of cells in G2/M phase and induce apoptosis. Neither Hp nor HA was genotoxic. The expression of CDK6 and CTP3A4 was reduced by Hp, and both HA and Hp caused a significant reduction of CYP1A2 and CYP3A4 expression. It is possible that the cytotoxicity caused by HA and Hp does not involve transcriptional regulation of the cyclins and CDKs tested but is instead related to the inhibition of metabolism. This is evidenced by the results of an MTT assay and changes in the expression of genes related to drug metabolism, leading to cell death. Indeed, the cells exhibited decreased proliferation upon exposure to Hp and HA. The data show that treatment with either Hp or HA can be cytotoxic, and this should be taken into consideration when balancing the risks and benefits of treatments for rheumatic diseases. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Proliferação de Células/efeitos dos fármacos , Glicosídeos/toxicidade , Inibidores do Crescimento/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Extratos Vegetais/toxicidade , Piranos/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glicosídeos/farmacologia , Inibidores do Crescimento/farmacologia , Harpagophytum/química , Células Hep G2 , Humanos , Extratos Vegetais/farmacologia , Piranos/farmacologia , Medição de Risco , Testes de Toxicidade
20.
Naunyn Schmiedebergs Arch Pharmacol ; 389(12): 1279-1288, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27592117

RESUMO

Monastrol is an allosteric inhibitor of the mitotic kinesin Eg5 that exhibits an antiproliferative effect against several cell lines. We investigated the antiproliferative effect of monastrol on human breast adenocarcinoma cells (MCF-7) and mammary epithelial cells (HB4a, non-tumoral). Monastrol treatment decreased cell viability only in MCF-7 tumor cells. Real-time cell growth kinetic analysis showed a decrease in the proliferation of MCF-7 cells exposed to monastrol, while in the HB4a cells, only a concentration of 100 µM was able to induce this effect. In a cell cycle analysis, exposure of MCF-7 cells to monastrol led to an increased population of cells in both the G1 and G2/M phases. In HB4a cells, the proportion of cells in the G2/M phase was increased. Monastrol led to an increased mitotic index in both cell lines. Monastrol was not able to induce cell death by apoptosis in any of the cell lines studied. Gene expression analysis was performed to measure the mRNA levels of cell cycle genes, DNA damage indicator gene, and apoptotic related genes. Treatment with monastrol induced in MCF-7 cells a 5-fold increase in the mRNA levels of the CDKN1A gene, an inhibitor of CDKs related with cell cycle arrest in response a stress stimulus, and a 2-fold decrease in CDKN1C mRNA levels in HB4a cells. These results provide evidence that monastrol has a greater antiproliferative effect on MCF-7 tumor cells compared with non-tumor HB4a cells; however, no selective is observed.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Glândulas Mamárias Humanas/efeitos dos fármacos , Pirimidinas/farmacologia , Tionas/farmacologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p57/genética , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Relação Dose-Resposta a Droga , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Cinética , Células MCF-7 , Glândulas Mamárias Humanas/metabolismo , Glândulas Mamárias Humanas/patologia , Índice Mitótico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
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