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1.
Int J Mol Sci ; 24(20)2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37894866

RESUMO

Chromolaena tacotana (Klatt) R. M. King and H. Rob (Ch. tacotana) contains bioactive flavonoids that may have antioxidant and/or anti-cancer properties. This study investigated the potential anti-cancer properties of a newly identified chalcone isolated from the inflorescences of the plant Chromolaena tacotana (Klatt) R. M. King and H. Rob (Ch. tacotana). The chalcone structure was determined using HPLC/MS (QTOF), UV, and NMR spectroscopy. The compound cytotoxicity and selectivity were evaluated on prostate, cervical, and breast cancer cell lines using the MTT assay. Apoptosis and autophagy induction were assessed through flow cytometry by detecting annexin V/7-AAD, active Casp3/7, and LC3B proteins. These results were supported by Western blot analysis. Mitochondrial effects on membrane potential, as well as levels of pro- and anti-apoptotic proteins were analyzed using flow cytometry, fluorescent microscopy, and Western blot analysis specifically on a triple-negative breast cancer (TNBC) cell line. Furthermore, molecular docking (MD) and molecular dynamics (MD) simulations were performed to evaluate the interaction between the compounds and pro-survival proteins. The compound identified as 2',3,4-trihydroxy-4',6'-dimethoxy chalcone inhibited the cancer cell line proliferation and induced apoptosis and autophagy. MDA-MB-231, a TNBC cell line, exhibited the highest sensitivity to the compound with good selectivity. This activity was associated with the regulation of mitochondrial membrane potential, activation of the pro-apoptotic proteins, and reduction of anti-apoptotic proteins, thereby triggering the intrinsic apoptotic pathway. The chalcone consistently interacted with anti-apoptotic proteins, particularly the Bcl-2 protein, throughout the simulation period. However, there was a noticeable conformational shift observed with the negative autophagy regulator mTOR protein. Future studies should focus on the molecular mechanisms underlying the anti-cancer potential of the new chalcone and other flavonoids from Ch. tacotana, particularly against predominant cancer cell types.


Assuntos
Chalcona , Chalconas , Chromolaena , Neoplasias de Mama Triplo Negativas , Humanos , Chalcona/farmacologia , Chalconas/farmacologia , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Neoplasias de Mama Triplo Negativas/metabolismo , Proliferação de Células , Apoptose
2.
Lancet ; 386(10009): 2145-91, 2015 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-26321261

RESUMO

BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.


Assuntos
Doença Crônica/epidemiologia , Doenças Transmissíveis/epidemiologia , Saúde Global/estatística & dados numéricos , Transição Epidemiológica , Expectativa de Vida , Ferimentos e Lesões/epidemiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade Prematura , Anos de Vida Ajustados por Qualidade de Vida , Fatores Socioeconômicos
3.
J Theor Biol ; 345: 43-51, 2014 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-24361327

RESUMO

GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and Unfolded Protein Response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and Heat Shock Proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and Molecular Dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.


Assuntos
Lesões Encefálicas/metabolismo , Proteínas de Choque Térmico/metabolismo , Modelos Biológicos , NF-kappa B/metabolismo , Biologia Computacional/métodos , Chaperona BiP do Retículo Endoplasmático , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular/métodos , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas/fisiologia , Mapeamento de Interação de Proteínas/métodos , Eletricidade Estática
4.
Plants (Basel) ; 13(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38475417

RESUMO

Breast cancer (BC) is one of the most common cancers among women. Effective treatment requires precise tailoring to the genetic makeup of the cancer for improved efficacy. Numerous research studies have concentrated on natural compounds and their anti-breast cancer properties to improve the existing treatment options. Chromolaena tacotana (Klatt) R.M. King and H. Rob (Ch. tacotana) is a notable source of bioactive hydroxy-methylated flavonoids. However, the specific anti-BC mechanisms of these flavonoids, particularly those present in the plant's inflorescences, remain partly undefined. This study focuses on assessing a chalcone derivative extracted from Ch. tacotana inflorescences for its potential to concurrently activate regulated autophagy and intrinsic apoptosis in luminal A and triple-negative BC cells. We determined the chemical composition of the chalcone using ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopy. Its selective cytotoxicity against BC cell lines was assessed using the MTT assay. Flow cytometry and Western blot analysis were employed to examine the modulation of proteins governing autophagy and the intrinsic apoptosis pathway. Additionally, in silico simulations were conducted to predict interactions between chalcone and various anti-apoptotic proteins, including the mTOR protein. Chalcone was identified as 2',4-dihydroxy-4',6'-dimethoxy-chalcone (DDC). This compound demonstrated a selective inhibition of BC cell proliferation and triggered autophagy and intrinsic apoptosis. It induced cell cycle arrest in the G0/G1 phase and altered mitochondrial outer membrane potential (∆ψm). The study detected the activation of autophagic LC3-II and mitochondrial pro-apoptotic proteins in both BC cell lines. The regulation of Bcl-XL and Bcl-2 proteins varied according to the BC subtype, yet they showed promising molecular interactions with DDC. Among the examined pro-survival proteins, mTOR and Mcl-1 exhibited the most favorable binding energies and were downregulated in BC cell lines. Further research is needed to fully understand the molecular dynamics involved in the activation and interaction of autophagy and apoptosis pathways in cancer cells in response to potential anticancer agents, like the hydroxy-methylated flavonoids from Ch. tacotana.

5.
Respir Res ; 14: 44, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23586347

RESUMO

BACKGROUND: Data describing real-life management and treatment of community-acquired pneumonia (CAP) in Europe are limited. REACH (http://NCT01293435) was a retrospective, observational study collecting data on the management of EU patients hospitalized with CAP. METHODS: Patients were aged ≥18 years, hospitalized with CAP between March 2010 and February 2011, and requiring in-hospital treatment with intravenous antibiotics. An electronic Case Report Form was used to collect patient, disease and treatment variables, including type of CAP, medical history, treatment setting, antibiotics administered and clinical outcomes. RESULTS: Patients (N = 2,039) were recruited from 128 centres in ten EU countries (Belgium, France, Germany, Greece, Italy, the Netherlands, Portugal, Spain, Turkey, UK). The majority of patients were aged ≥65 years (56.4%) and had CAP only (78.8%). Initial antibiotic treatment modification occurred in 28.9% of patients and was more likely in certain groups (patients with comorbidities; more severely ill patients; patients with healthcare-associated pneumonia, immunosuppression or recurrent episodes of CAP). Streamlining (de-escalation) of therapy occurred in 5.1% of patients. Mean length of hospital stay was 12.6 days and overall mortality was 7.2%. CONCLUSION: These data provide a current overview of clinical practice in patients with CAP in EU hospitals, revealing high rates of initial antibiotic treatment modification. The findings may precipitate reassessment of optimal management regimens for hospitalized CAP patients.


Assuntos
Infecções Comunitárias Adquiridas/terapia , Pneumonia/terapia , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Europa (Continente) , Feminino , Hospitalização , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Cell Biol Int ; 37(6): 521-32, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23494837

RESUMO

Glucose-regulated protein 78 (GRP78; 78 kDa) belongs to a group of highly conserved heat shock proteins (Hsp) with important functions at the cellular level. The emerging interest for GRP78 relies on its different functions, both in normal and pathological circumstances. GRP78 regulates intracellular calcium, protein shaping, endoplasmic reticulum (ER) stress and cell survival by an immediate response to insults, and that its expression may also be regulated by estrogens. Although these roles are well explored, the mechanisms by which GRP78 induces these changes are not completely understood. In this review, we highlight various aspects related to the GRP78 functioning in cellular protection and repair in response to ER stress and unfolded protein response by the regulation of intracellular Ca(2+) and other mechanisms. In this respect, the novel interactions between GRP78 and estrogens, such as estradiol and others, are analyzed in the context of the central nervous system (CNS). We also discuss the importance of GRP78 and estrogens in brain diseases including ischemia, Alzheimer's and Huntington's disorders. Finally, the main protective mechanisms of GRP78 and estrogens during ER dysfunction in the brain are described, and the prospective roles of GRP78 in therapeutic processes.


Assuntos
Encéfalo/metabolismo , Estrogênios/metabolismo , Proteínas de Choque Térmico/metabolismo , Resposta a Proteínas não Dobradas/fisiologia , Animais , Sítios de Ligação , Cálcio/metabolismo , Chaperona BiP do Retículo Endoplasmático , Humanos
7.
Arch Physiol Biochem ; 129(5): 1058-1070, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33689540

RESUMO

We investigated how oxidative stress (OS) alters Ca2+ handling in ventricular myocytes in early metabolic syndrome (MetS) in sucrose-fed rats. The effects of N-acetyl cysteine (NAC) or dl-Dithiothreitol (DTT) on systolic Ca2+ transients (SCaTs), diastolic Ca2+ sparks (CaS) and Ca2+ waves (CaW), recorded by confocal techniques, and L-type Ca2+ current (ICa), assessed by whole-cell patch clamp, were evaluated in MetS and Control cells. MetS myocytes exhibited decreased SCaTs and CaS frequency but unaffected CaW propagation. In Control cells, NAC/DTT reduced RyR2/SERCA2a activity blunting SCaTs, CaS frequency and CaW propagation, suggesting that basal ROS optimised Ca2+ signalling by maintaining RyR2/SERCA2a function and that these proteins facilitate CaW propagation. Conversely, NAC/DTT in MetS recovered RyR2/SERCA2a function, improving SCaTs and CaS frequency, but unexpectedly decreasing CaW propagation. We hypothesised that OS decreases RyR2/SERCA2a activity at early MetS, and while decreased SERCA2a favours CaW propagation, diminished RyR2 restrains it.


Assuntos
Síndrome Metabólica , Canal de Liberação de Cálcio do Receptor de Rianodina , Ratos , Animais , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/farmacologia , Síndrome Metabólica/metabolismo , Miócitos Cardíacos , Estresse Oxidativo
8.
Cells ; 11(15)2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35954153

RESUMO

Several studies have identified main changes in T- and B-lymphocyte subsets during chronic HIV infection, but few data exist on how these subsets behave during the initial phase of HIV infection. We enrolled 22 HIV-infected patients during the acute stage of infection before the initiation of antiretroviral therapy (ART). Patients had blood samples drawn previous to ART initiation (T0), and at 2 (T1) and 12 (T2) months after ART initiation. We quantified cellular HIV-DNA content in sorted naïve and effector memory CD4 T cells and identified the main subsets of T- and B-lymphocytes using an 18-parameter flow cytometry panel. We identified correlations between the patients' clinical and immunological data using PCA. Effective HIV treatment reduces integrated HIV DNA in effector memory T cells after 12 months (T2) of ART. The main changes in CD4+ T cells occurred at T2, with a reduction of activated memory, cytolytic and activated/exhausted stem cell memory T (TSCM) cells. Changes were present among CD8+ T cells since T1, with a reduction of several activated subsets, including activated/exhausted TSCM. At T2 a reduction of plasmablasts and exhausted B cells was also observed. A negative correlation was found between the total CD4+ T-cell count and IgM-negative plasmablasts. In patients initiating ART immediately following acute/early HIV infection, the fine analysis of T- and B-cell subsets has allowed us to identify and follow main modifications due to effective treatment, and to identify significant changes in CD4+ and CD8+ T memory stem cells.


Assuntos
Infecções por HIV , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Infecções por HIV/tratamento farmacológico , Humanos , Memória Imunológica , Células-Tronco
9.
Salud Publica Mex ; 52 Suppl 1: S19-26, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20585724

RESUMO

OBJECTIVE: To describe the prevalence, distribution and degree of control of type 2 diabetes (T2D) in Mexican population. MATERIAL AND METHODS: Subjects were classified as previously diagnosed T2D (PD); or as "finding of the survey" (FS) (glucose >or=126 mg/dL). Hemoglobin A1c was measured in PD-subjects. RESULTS: The prevalence for PD-T2D was 7.34% (95%CI 6.3, 8.5) and for FS 7.07% (95%CI 6.1, 8.1), summing 14.42%; (7.3 million diabetics). 5.3% of PD-T2D were in good, 38.4% in poor and 56.2% very poor control. Older age (OR=0.96, 95%CI 0.94, 0.97), lower BMI (OR=0.95, 95%CI 0.91, 1.0), were protective for poor control. Affiliation to private services (OR=1.77, 95%CI 0.98, 3.13), larger T2D duration (OR=1.05, 95%CI 1.01, 1.08), and combining oral medication and insulin (OR=16.1, 95%CI 1.61, 161) were riskier. CONCLUSIONS: We found an alarming prevalence of T2D in Mexican population; the majority of PD diabetics are in poor control. Research on the latter is warranted.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Inquéritos Epidemiológicos , Inquéritos Nutricionais , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Dieta para Diabéticos , Jejum/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Rural , Estudos de Amostragem , População Urbana , Adulto Jovem
10.
Arch Cardiol Mex ; 90(4): 427-435, 2020 09 02.
Artigo em Espanhol | MEDLINE | ID: mdl-33008146

RESUMO

BACKGROUND: Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in the adult population worldwide. Most studies on risk factors have focused on children and adults of mature age. Quite the opposite, there are few which specifically analyze young individuals. OBJECTIVES: The objectives of the study were to determine cardiovascular risk factors in young Mexican adults. MATERIALS AND METHODS: A cross-sectional, descriptive, and observational study was carried out on a healthy sample of 198 young Mexican university-level adults, aged from 18 to 25 years who, after completing a questionnaire, were evaluated on anthropometric and blood pressure parameters. A comparative analysis of the results was made according to sex and with findings from other studies. RESULTS: In 46% of the subjects, an atherogenic diet was identified (predominant among males). About 59.1% of the individuals were classified as sedentary (mostly women). About 91.4% of the sample had two or more associated antecedents of CVD (and other associated conditions) in their family background, the most frequent being diabetes mellitus (71.2%), systemic hypertension (64.6%), and overweight or obesity (56.6%). In 25.8% of the individuals, overweight was observed (more frequent among women). In males, a higher proportion of alterations in blood pressure levels was described. CONCLUSIONS: The most frequently identified findings correspond to the group of modifiable minor risk factors, which could allow the development of preventive measures, inasmuch as these are subjects in which the modification of harmful behaviors and habits is achievable and timely.

11.
Metab Eng ; 11(4-5): 274-83, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19508897

RESUMO

Fatty liver is a significant risk factor for liver transplantation, and accounts for nearly half of the livers rejected from the donor pool. We hypothesized that metabolic preconditioning via ex vivo perfusion of the liver graft can reduce fat content and increase post-transplant survival to an acceptable range. We describe a perfusate medium containing agents that promote the defatting of hepatocytes and explanted livers. Defatting agents were screened on cultured hepatocytes made fatty by pre-incubation with fatty acids. The most effective agents were then used on fatty livers. Fatty livers were isolated from obese Zucker rats and normothermically perfused with medium containing a combination of defatting agents. This combination decreased the intracellular lipid content of cultured hepatocytes by 35% over 24h, and of perfused livers by 50% over 3h. Metabolite analysis suggests that the defatting cocktail upregulated both lipid oxidation and export. Furthermore, gene expression analysis for several enzymes and transcription factors involved in fatty acid oxidation and triglyceride clearance were elevated. We conclude that a cocktail of defatting agents can be used to rapidly clear excess lipid storage in fatty livers, thus providing a new means to recondition donor livers deemed unacceptable or marginally acceptable for transplantation.


Assuntos
Fígado Gorduroso/metabolismo , Transplante de Fígado , Perfusão/métodos , Doadores de Tecidos , Animais , Técnicas de Cultura de Células , Sobrevivência Celular , Células Cultivadas , Feminino , Hepatócitos/citologia , Heterozigoto , Homozigoto , Humanos , Ratos , Ratos Endogâmicos Lew , Ratos Zucker , Análise de Sobrevida , Fatores de Tempo
12.
J Neurosci Methods ; 168(1): 35-41, 2008 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-17949822

RESUMO

None of experimental models used to study the toxic effect of unconjugated bilirubin brain accumulation, reproduce the conditions in which the hyperbilirubinemia is a consequence of a hemolytic process, i.e. when important amounts of bilirubin and iron are released. The aim was to develop an animal model to determine the role of bilirubin and iron, in the encephalopathy secondary to a hemolytic disease. Male Wistar rats 7 days old (n=30) were treated with phenylhydrazine as hemolytic at 75 mg/kg body weight intraperitoneally for 2 days and euthanized 24 h after the last dose. Hemoglobin, hematocrit, serum and brain bilirubin, serum iron and lipoperoxidation products, as well as neuronal damage and iron positive staining were evaluated and compared among treated and untreated (n=10) animals. The animals with induced hemolysis showed significant reduction in hemoglobin and hematocrit, increased concentration of total and conjugated bilirubin, as well as of serum iron and lipid peroxidation products. The neuronal damage in treated animals included the presence of altered neurons spread out among normal cells, as well as of iron-staining positive cells. With the use of appropriated pharmacological procedures, the characteristics of the model can be useful to dissect the participation of both bilirubin and iron, on the bilirubin encephalopathy secondary to hemolysis.


Assuntos
Encéfalo/metabolismo , Hemólise/fisiologia , Kernicterus/patologia , Animais , Animais Recém-Nascidos , Bilirrubina/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Hematócrito/métodos , Hemoglobinas/metabolismo , Hemólise/efeitos dos fármacos , Ferro/sangue , Kernicterus/induzido quimicamente , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Neurônios/metabolismo , Neurônios/patologia , Fenil-Hidrazinas , Ratos , Ratos Wistar
13.
Genes (Basel) ; 8(11)2017 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-29113111

RESUMO

Chronic exposure to elevated glucose levels leads to fatty acid accumulation, which promotes the development of metabolic diseases such as obesity and type 2 diabetes. MXL-3 is a conserved transcriptional factor that modulates the inhibition of lipolysis in Caenorhabditis elegans. However, the role of MXL-3 in lipid metabolism during nutrient excess remains unknown. We hypothesized that inhibition of MXL-3 prevents glucose-dependent fat accumulation. Nematodes from wild-type N2, MXL-3::GFP and sbp-1 or mxl-3 null strains were grown on standard, high glucose or high glucose plus metformin plates for 24 h. Using laser-scanning confocal microscopy, we monitored the glucose-induced activation of MXL-3 labeled with GFP (MXL-3::GFP). Lipid levels were determined by Oil Red O (ORO) staining and gas chromatography/mass spectrometry, and gene expression was assessed by qRT-PCR. We found that high glucose activated MXL-3 by increasing its rate of nuclear entry, which in turn increased lipid levels via sterol regulatory element-binding protein (SBP-1). This activated critical genes that synthesize long chain unsaturated fatty acids (MUFAs and PUFAs) and repress lipolytic genes. Interestingly, the anti-diabetic drug metformin inhibited MXL-3 activation and subsequently prevented glucose-dependent fat accumulation. These findings highlight the importance of the MXL-3/SBP-1 axis in the regulation of lipid metabolism during nutritional excess and provide new insight into the mechanism by which metformin prevents lipid accumulation. This study also suggests that inhibition of MXL-3 may serve as a potential target for the treatment of chronic metabolic diseases, including obesity, type 2 diabetes, and cardiovascular disease.

14.
Motrivivência (Florianópolis) ; 33(64): 1-14, Mar. 2021.
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1150487

RESUMO

O objetivo deste estudo foi apresentar e analisar o perfil dos gestores responsáveis pelo esporte e lazer de 15 municípios do Território de Identidade Litoral Sul da Bahia, buscando gerar reflexões em torno das possibilidades de desenvolvimento das políticas públicas da região. A coleta de dados foi realizada por meio de um questionário virtual utilizando o Google Formulários, em um primeiro momento, e posteriormente in loco. Como resultado, os dados apontaram para a necessidade de se discutir a importância da capacitação/especialização dos gestores no que tange ao fomento ao lazer e ao esporte, compreendidos nesta pesquisa como direitos do cidadão e, portanto, objetos de uma consistente e regular política pública para os municípios da região.


The aim of this study was to present and analyze the profile of managers responsible for sports and leisure in 15 municipalities in the Southern Coastal Identity Territory of Bahia, seeking to generate reflections on the possibilities of developing public policies in the region. Data collection was performed through a virtual questionnaire using Google Forms, at first, and in loco. As a result, the data pointed to the need to discuss the importance of training/specialization of managers in terms of promoting leisure and sport, understood in this research as citizens' rights and therefore, objects of a consistent and regular public policy for municipalities in the region.


El objetivo de este estudio fue presentar y analizar el perfil de los gestores responsables por el sector de deporte y ocio en 15 municipios del Territorio de Identidad Litoral Sur de Bahía, buscando generar reflexiones sobre las posibilidades de desarrollo de políticas públicas en la región. Para ello, la recogida de datos se realizó inicialmente mediante un cuestionario virtual en Google Forms, y después, en el sitio. Como resultado, los datos señalaron a la necesidad de discutir la importancia de la formación/capacitación de los gestores respeto a la promoción del ocio y del deporte, entendidos en esta investigación como pautas de ciudadanía y, por consiguiente, que deben ser objeto de una coherente y regular política pública para los municipios de la región.

15.
Arch. cardiol. Méx ; 90(4): 427-435, Oct.-Dec. 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1152817

RESUMO

Abstract Background: Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in the adult population worldwide. Most studies on risk factors have focused on children and adults of mature age. Quite the opposite, there are few which specifically analyze young individuals. Objectives: The objectives of the study were to determine cardiovascular risk factors in young Mexican adults. Materials and methods: A cross-sectional, descriptive, and observational study was carried out on a healthy sample of 198 young Mexican university-level adults, aged from 18 to 25 years who, after completing a questionnaire, were evaluated on anthropometric and blood pressure parameters. A comparative analysis of the results was made according to sex and with findings from other studies. Results: In 46% of the subjects, an atherogenic diet was identified (predominant among males). About 59.1% of the individuals were classified as sedentary (mostly women). About 91.4% of the sample had two or more associated antecedents of CVD (and other associated conditions) in their family background, the most frequent being diabetes mellitus (71.2%), systemic hypertension (64.6%), and overweight or obesity (56.6%). In 25.8% of the individuals, overweight was observed (more frequent among women). In males, a higher proportion of alterations in blood pressure levels was described. Conclusions: The most frequently identified findings correspond to the group of modifiable minor risk factors, which could allow the development of preventive measures, inasmuch as these are subjects in which the modification of harmful behaviors and habits is achievable and timely.


Resumen Antecedentes: Las enfermedades cardiovasculares (ECV) son la principal causa de morbimortalidad en la población adulta a nivel mundial. La mayor parte de los estudios sobre factores de riesgo han focalizado su atención en niños y adultos de edad madura. Por el contrario, resultan escasos aquellos que analicen específicamente individuos jóvenes. Objetivo: Determinar los factores de riesgo cardiovascular en adultos jóvenes mexicanos. Material y métodos: Estudio observacional, descriptivo y transversal, realizado en una muestra sana de 198 adultos jóvenes mexicanos de nivel universitario de 18 a 25 años a quienes, tras completar un cuestionario, se les evaluaron parámetros antropométricos y de tensión arterial. Se hizo un análisis comparativo de los resultados de acuerdo con el sexo y con hallazgos de otros estudios. Resultados: En el 46% de los sujetos se identificó una dieta aterogénica (predominante entre varones). El 59.1% de los individuos se clasificaron como sedentarios (en su mayoría mujeres). El 91.4% de la muestra cuenta con dos o más antecedentes heredofamiliares de ECV (y otras condiciones asociadas), siendo los más frecuentes la diabetes mellitus (71.2%), la hipertensión arterial sistémica (64.6%) y el sobrepeso u obesidad (56.6%). El 25.8% de los individuos cursó con sobrepeso (más frecuente entre mujeres). En los varones se presentó una mayor proporción de alteraciones en los niveles de tensión arterial. Conclusiones: Los hallazgos identificados con mayor frecuencia corresponden al grupo de factores de riesgo menores modificables, lo cual podría permitir el desarrollo de medidas preventivas, al tratarse de sujetos en quienes es asequible la modificación de conductas y hábitos nocivos.

16.
Int. j. morphol ; 38(2): 458-460, abr. 2020.
Artigo em Inglês | LILACS | ID: biblio-1056462

RESUMO

The study of the temporomandibular joint (TMJ) through imaging, is useful for the analysis of intra-articular procedures in view of its complex anatomy. Precise knowledge of the depth at which the TMJ is located is required to achieve an ideal puncture technique. The aim of this study was to measure the depth of the TMJ through magnetic resonance imaging (MRI) in patients with temporomandibular disorders (TMD). A cross-sectional study was conducted, selecting 150 MRI of patients who attended the Polyclinic for TMD and Orofacial Pain. The variables analyzed were: 1) Depth of the right and left TMJ; 2) Age of the patients; and 3) Sex of the patients. Of the total MR, 114 corresponded to women with a median age of 23 years. The median depth of the right TMJ was 17.16 mm and median on the left side was 16.98 mm, there was no statistically significant difference (p> 0.05) but there was a strong correlation (r = 0.842). There were no differences between the depths and the sex of the patients in both the right and left TMJ. There was no correlation between age and depth of TMJ. In conclusion the depth of the right and left condyle are highly correlated, being approximately 17 mm according to the population studied. There is no association between patient age and condylar depth, and there are no differences in average according to sex.


El estudio por imágenes de la articulación temporomandibular (ATM) es útil para el análisis de procedimientos intra-articulares debido a la compleja anatomía que presenta. Se requiere un conocimiento preciso de la profundidad a la cual se encuentra la ATM para una adecuada técnica de punción. El objetivo de este estudio fue medir la profundidad de laATM en relación a la piel a través de resonancia magnética (RM) en pacientes con trastornos temporomandiblaes (TTM). Se realizó un estudio transversal, seleccionando 150 RM de pacientes que asistieron al Policlínico de TTM y Dolor Orofacial. La variables analizadas fueron: 1) Profundidad de la ATM derecha e izquierda; 2) Edad de los pacientes; y 3) Sexo de los pacientes. Del total de RM, 114 correspondían a mujeres con una mediana de edad de 23 años. La mediana de la profundidad de la ATM derecha fue de 17,16 mm y la mediana del lado izquierdo fue de 16,98 mm, no hubo una diferencia estadísticamente significativa (p>0,05) pero si una fuerte correlación (r=0,842). No hubo diferencias entre las profundidades y el sexo de los pacientes tanto en la ATM derecha como en la izquierda. No hubo correlación entre la edad y la profundidad de la ATM. La profundidad de los cóndilos derecho e izquierdo están altamente correlacionados, siendo 17 mm aproximadamente en la población estudiada. No existe asociación entre la edad de los pacientes y la profundidad condilar, y no hay diferencias en promedios por sexo.


Assuntos
Humanos , Masculino , Feminino , Adulto , Imageamento por Ressonância Magnética , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Côndilo Mandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/patologia , Estudos Transversais
17.
Neurosci Lett ; 565: 2-6, 2014 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-24394907

RESUMO

Cortical spreading depression (CSD) is a presumably pathophysiological phenomenon that interrupts local cortical function for periods of minutes to hours. This phenomenon is important due to its association with different neurological disorders such as migraine, malignant stroke and traumatic brain injury (TBI). Glial cells, especially astrocytes, play an important role in the regulation of CSD and in the protection of neurons under brain trauma. The correlation of TBI with CSD and the astrocytic function under these conditions remain unclear. This review discusses the possible link of TBI and CSD and its implication for neuronal survival. Additionally, we highlight the importance of astrocytic function for brain protection, and suggest possible therapeutic strategies targeting astrocytes to improve the outcome following TBI-associated CSD.


Assuntos
Astrócitos/fisiologia , Lesões Encefálicas/fisiopatologia , Depressão Alastrante da Atividade Elétrica Cortical , Animais , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Sobrevivência Celular , Metabolismo Energético , Aminoácidos Excitatórios/metabolismo , Humanos , Neurônios/patologia , Neurônios/fisiologia , Espécies Reativas de Oxigênio/metabolismo
18.
Licere (Online) ; 19(3)set. 2016. tab
Artigo em Português | LILACS | ID: biblio-846921

RESUMO

O presente estudo foi realizado no município de Coaraci ­ BA, tendo como objetivo geral, investigar como o Centro Educacional de Coaraci (CEC) pode contribuir no processo de ampliação da democratização do acesso ao lazer na cidade. Essa pesquisa de cunho qualitativo e quantitativo utilizou a abordagem de estudo de caso. Para atingir os objetivos foram aplicados questionários mistos e aberto aos sujeitos envolvidos no cotidiano escolar (alunos, professores, diretor e pais). Os resultados foram discutidos com diversos teóricos que tratam de questões ligadas à educação, ao lazer, e especificamente ao programa escola aberta. Conclui-se que a maioria dos depoentes indicam um potencial no CEC para implantação do projeto supracitado e para ampliação da democratização ao acesso do lazer em Coaraci, através da implementação da Escola Aberta, porém ainda existem poucas iniciativas, sobretudo do poder público e muitas dificuldades para uma melhor relação da escola com a comunidade na realização das atividades de lazer.


The present study was conducted in the municipality of Coaraci-BA, with the overall objective, investigate how the educational center of Itacaré (CEC) can contribute to the process of enlargement of the democratization of access to leisure in the city. This qualitative and quantitative-oriented research used the case study approach. To achieve the objectives were mixed and open to questionnaires applied subjects involved in the daily school (students, teachers and parents). The results were discussed with different theorists dealing with issues related to education, leisure, and specifically to open school program. It appears that the majority of subjects indicate a potential in the CEC for the implementation of the aforementioned project and expansion of democratization in Coaraci access, through the implementation of open school, however there are still a few initiatives, in particular the Government and many difficulties for a better relationship with the school community in the implementation of leisure activities.


Assuntos
Demografia , Cidades , Democracia , Educação , Atividades de Lazer
20.
Int. j. morphol ; 32(2): 531-536, jun. 2014. ilus
Artigo em Espanhol | LILACS | ID: lil-714304

RESUMO

La encefalopatía por hipoxia es causa de discapacidad y requiere de nuevas estrategias terapéuticas. El pirofosfato de tiamina (PPT) es un cofactor esencial de enzimas fundamentales en el metabolismo de la glucosa, cuya disminución puede conducir a la falla en la síntesis de ATP y a la muerte celular. El objetivo de este estudio fue determinar si la administración de PPT, puede reducir el daño celular en un modelo de hipoxia neonatal en ratas. Animales de 11 días de edad fueron tratados con PPT (130 mg/kg) en dosis única o solución salina, una hora antes del protocolo de hipoxia o al término de ésta. Los cerebros fueron colectados para la evaluación del daño celular. Además, se tomaron muestras sanguíneas para evaluar los indicadores gasométricos de presión de dióxido de carbono (PaCO2) y de oxígeno (PaO2) en sangre arterial y pH. Los resultados muestran que la administración de PPT previa a la inducción de hipoxia, reduce el daño celular y restablece los indicadores gasométricos. Estos datos indican que el uso de PPT reduce el daño inducido por la hipoxia en animales neonatos.


Hypoxic encephalopathy is a leading cause of disability and requires new therapeutic strategies. Thiamine pyrophosphate (TPP) is an essential cofactor of fundamental enzymes involved in glucose metabolism. TPP reduction may lead to ATP synthesis failure and cell death. The objective of this study was to determine if TPP administration can reduce cellular damage in a model of neonatal hypoxia in rats. Eleven day old animals were treated with TPP (130 mg/kg) as a single dose or with saline solution one hour before the hypoxia protocol or after ending the protocol. The brains were collected to evaluate cellular damage. Blood samples were also collected to evaluate arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2) and acidity (pH). The results showed that TPP administration previous to hypoxia induction reduces cellular damage and reestablishes arterial blood gases. These data indicate that TPP use reduces the damage induced by hypoxia in neonatal animals.


Assuntos
Animais , Masculino , Ratos , Tiamina Pirofosfato/administração & dosagem , Apoptose/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Hipóxia/tratamento farmacológico , Oxigênio/sangue , Tiamina Pirofosfato/farmacologia , Gasometria , Encefalopatias/prevenção & controle , Ratos Wistar , Substâncias Protetoras/farmacologia , Modelos Animais de Doenças , Concentração de Íons de Hidrogênio , Animais Recém-Nascidos
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