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1.
Mult Scler Relat Disord ; 82: 105373, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154347

RESUMO

BACKGROUND: The modulation of the activity disease in patients with Multiple Sclerosis (MS) that occurs during pregnancy is a helpful model which could provide insight into central disease mechanisms and facilitate treatment. Therefore, the aim of the study was to identify differentially expressed genes in-silico to perform biological function pathway enrichment analysis and protein-protein interaction from pregnant women with MS. METHODS: Transcriptome data were obtained from the Gene Expression Omnibus (GEO) database. We selected the microarray dataset GSE17449. The gene expression dataset contains the data of mononuclear cells from four different groups sought, including seven healthy women (H), four healthy pregnant women (HP), eight women with multiple sclerosis (WMS), and nine women nine months pregnant with multiple sclerosis (PMS). The GSEA software was employed for enrichment analysis, and the REACTOME database was used for biological pathways. The protein-protein interaction (PPI) network was plotted with STRING. The databases used to identify the connection of DEGs with different signaling pathways were KEGG and WIKIPATHWAYS. RESULTS: We identified 42 differentially expressed genes in pregnant women with MS. The significant pathways included IL-10 signaling pathway, ErbB2 activates, the hemoglobin complex (HBD, HBB, HBA1, AHSP, and HBA2), IL-17 signaling pathway (LCN2 and MMP9), antigen processing and presentation, and Th17 cell differentiation (HLA-DQA1), Rap1 signaling pathway (ID1), NOD-Like receptor signaling pathway (CAMP and DEFA4), PD-L1 Signaling, Interferon gamma signaling (MMP9 and ARG1), Neutrophil degranulation (CAMP, DEFA4, ELANE, CEACAM8, S100P, CHI3L1, AZU1, OLFM4, CRISP3, LTF, ARG1, PGLYRP1, and TCN1). In the WIKIPATHWAYS set, significance was found Vitamin B12 metabolism (TCN1, HBB, and HBA2), and IL-18 signaling pathway (S100P). CONCLUSION: This study can be used to understand several essential target genes and pathways identified in the present study, which may serve as feasible targets for MS therapies.


Assuntos
Metaloproteinase 9 da Matriz , Esclerose Múltipla , Gravidez , Humanos , Feminino , Esclerose Múltipla/genética , Transcriptoma , Mapas de Interação de Proteínas , Biologia Computacional , Proteínas Sanguíneas , Chaperonas Moleculares
2.
Int J Mol Sci ; 24(24)2023 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-38139395

RESUMO

During the antiretroviral era, individuals living with HIV continue to experience milder forms of HIV-associated neurocognitive disorder (HAND). Viral proteins, including Tat, play a pivotal role in the observed alterations within the central nervous system (CNS), with mitochondrial dysfunction emerging as a prominent hallmark. As a result, our objective was to examine the expression of genes associated with mitophagy and mitochondrial biogenesis in the brain exposed to the HIV-1 Tat protein. We achieved this by performing bilateral stereotaxic injections of 100 ng of HIV-1 Tat into the hippocampus of Sprague-Dawley rats, followed by immunoneuromagnetic cell isolation. Subsequently, we assessed the gene expression of Ppargc1a, Pink1, and Sirt1-3 in neurons using RT-qPCR. Additionally, to understand the role of Tert in telomeric dysfunction, we quantified the activity and expression of Tert. Our results revealed that only Ppargc1a, Pink1, and mitochondrial Sirt3 were downregulated in response to the presence of HIV-1 Tat in hippocampal neurons. Interestingly, we observed a reduction in the activity of Tert in the experimental group, while mRNA levels remained relatively stable. These findings support the compelling evidence of dysregulation in both mitophagy and mitochondrial biogenesis in neurons exposed to HIV-1 Tat, which in turn induces telomeric dysfunction.


Assuntos
Infecções por HIV , HIV-1 , Transtornos Neurocognitivos , Sirtuína 3 , Produtos do Gene tat do Vírus da Imunodeficiência Humana , Animais , Ratos , Produtos do Gene tat/metabolismo , Infecções por HIV/metabolismo , HIV-1/metabolismo , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/virologia , Neurônios/metabolismo , Biogênese de Organelas , Proteínas Quinases/metabolismo , Ratos Sprague-Dawley , Sirtuína 3/genética , Sirtuína 3/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
3.
Int J Mol Sci ; 23(2)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35054829

RESUMO

HIV-Associated neurocognitive disorder (HAND) is one of the major concerns since it persists in 40% of this population. Nowadays, HAND neuropathogenesis is considered to be caused by the infected cells that cross the brain-blood barrier and produce viral proteins that can be secreted and internalized into neurons leading to disruption of cellular processes. The evidence points to viral proteins such as Tat as the causal agent for neuronal alteration and thus HAND. The hallmarks in Tat-induced neurodegeneration are endoplasmic reticulum stress and mitochondrial dysfunction. Sirtuins (SIRTs) are NAD+-dependent deacetylases involved in mitochondria biogenesis, unfolded protein response, and intrinsic apoptosis pathway. Tat interaction with these deacetylases causes inhibition of SIRT1 and SIRT3. Studies revealed that SIRTs activation promotes neuroprotection in neurodegenerative diseases such Alzheimer's and Parkinson's disease. Therefore, this review focuses on Tat-induced neurotoxicity mechanisms that involve SIRTs as key regulators and their modulation as a therapeutic strategy for tackling HAND and thereby improving the quality of life of people living with HIV.


Assuntos
Infecções por HIV/psicologia , Doenças Neurodegenerativas/metabolismo , Sirtuínas/metabolismo , Estresse do Retículo Endoplasmático , Regulação da Expressão Gênica , Infecções por HIV/metabolismo , Humanos , Qualidade de Vida , Resposta a Proteínas não Dobradas
4.
Mol Biol Rep ; 48(5): 4247-4252, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34097204

RESUMO

Among the host restriction factors against HIV, SERINC5 has been described in vitro, but the mRNA level of SERINC5 in vivo has been little studied. We compare SERINC5 expression in subjects with HIV-1 (highly active antiretroviral treatment (HAART) and HAART-naïve) with and without suppression of viral load. A cross-sectional study was performed with 107 individuals distributed as follows: 24 with HAART-naïve and detectable viral load (> 50 copies/mL), 13 with HAART and detectable viral load (> 50 copies/mL), 50 with HAART and undetectable viral load (≤ 50 copies/mL), and 20 without HIV-1. SERINC5 expression in buffy coats was determined using RT-qPCR. The viral load was determined using real-time PCR and the amount of CD4 + and CD8 + T-lymphocytes was measured using flow cytometry. The data were normalized with the Shapiro-Wilk test and the Kruskal-Wallis test was subsequently performed. The relative expression was compared with a T-test and the remaining data with the Mann-Whitney U-test. ANCOVA multiple linear regression analysis was performed between characteristics of patients with SERINC5 expression. The mean and SD of the SERINC5 expression in the three groups with HIV-1 was 0.9 ± 0.2 and without HIV-1 was 1.7 ± 0.14 (P < 0.001). Multiple linear regression did not show the participation of CD4 +, CD8 + , viral load, infection time, or treatment time. No differences in the SERINC5 expression were found among the studied groups of patients with HIV-1. When comparing the groups with and without HIV-1 infection, SERINC5 was downregulation in the HIV-1 groups.


Assuntos
Buffy Coat/metabolismo , Regulação para Baixo/genética , Infecções por HIV/sangue , Infecções por HIV/genética , HIV-1/genética , Proteínas de Membrana/genética , Carga Viral/métodos , Adolescente , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade/métodos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Resultado do Tratamento , Adulto Jovem
5.
Genet Mol Biol ; 43(3): e20200017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584920

RESUMO

MicroRNAs are considered as potential biomarkers, agents, or therapeutic targets; few studies have addressed the expression of miRNAs in treatment-naïve patients infected with HIV-1. The aim of this study was to assess plasma relative circulating miRNA expression profiles in treatment-naïve Mexican patients with HIV/AIDS and healthy individuals using a commercial array. A low CD4+ T cell count and high viral load were found in all patients. Decreased relative miRNA-296-5p expression was observed in patients; moreover, this was the only miRNA that showed differences between the two groups. Thus, we measured the absolute expression of miR-296-5p by qPCR, confirming the result with statistically significant differences (P < 0.05). There is evidence that miR-296-5p regulates the expression of the PIN1 gene, which encodes the peptidylprolyl Cis/Trans isomerase NIMA-Interacting-1, that is involved in different stages of the biological cycle of HIV-1, this relationship is corroborated by bioinformatics analysis and ELISA assay was used to measure plasma levels of PIN1. The decreased expression of miR-296-5p found in naïve patients with HIV infection suggests a regulatory activity of this miRNA on virus replication, making it a potential therapeutic agent against HIV. Finally, miR-296-5p could be inhibiting the virus transcription by regulating genes different than PIN1.

6.
Biosci Rep ; 40(5)2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32319513

RESUMO

MicroRNAs (miRNAs/miRs) may serve as therapeutic agents or targets in diseases in which the expression of proteins plays an important role. The aim of the present study was to compare the expression levels of specific miRNAs, as well as their correlation with markers of response to antiretroviral (ARV) therapy, in patients with human immunodeficiency virus type 1 (HIV-1) infection with and without resistance to highly active antiretroviral therapy (HAART). METHODS: miRNA assays were performed on plasma samples obtained from 20 HIV-1-positive patients. A total of ten patients were divided into two groups: HAART-responsive and HAART-resistant (n=5 per group). Commercial arrays were subsequently used to identify 84 miRNAs. A total of three differentially expressed miRNAs were selected and analyzed by quantitative PCR (qPCR). Five other patients were subsequently added to each group for a new relative expression analysis. The absolute expression level of the two miRNAs was obtained and compared using the Student's t test. Receiver operating characteristic (ROC) curves were used to identify patients with antiretroviral therapy (ART) resistance. RESULTS: The array analysis revealed that miR-15b-5p, miR-16-5p, miR-20a-5p, miR-26a-5p, miR-126-3p and miR-150-5p were down-regulated in patients with HAART-resistance comparing with HAART-responsive. The expression levels of miR-16-5p, miR-26a-5p and miR-150-5p were confirmed using qPCR. The area under the ROC curve was 1.0 for the three miRNAs. CONCLUSIONS: The lower expression levels of miR-16-5p and miR-26a-5p in patients with HAART-resistance suggested that these may serve as potential biomarkers for the identification of HAART-responsive patients.


Assuntos
Fármacos Anti-HIV/uso terapêutico , MicroRNA Circulante/sangue , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , MicroRNAs/sangue , Adulto , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Biomarcadores/sangue , MicroRNA Circulante/genética , Estudos Transversais , Regulação para Baixo , Infecções por HIV/sangue , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/patogenicidade , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
8.
Pharmaceuticals (Basel) ; 10(3)2017 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-28684694

RESUMO

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that its pathogenesis is associated with oxidative stress and inflammation. Recent studies have suggested a protective role of the cannabinoid signalling system in PD. ß-caryophyllene (BCP) is a natural bicyclic sesquiterpene that is an agonist of the cannabinoid type 2 receptor (CB2R). Previous studies have suggested that BCP exerts prophylactic and/or curative effects against inflammatory bowel disease through its antioxidative and/or anti-inflammatory action. The present study describes the neuroprotective effects of BCP in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine model of PD, and we report the results of our investigation of its neuroprotective mechanism in neurons and glial cells. In the murine model, BCP pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in the SN and striatum, and alleviated MPTP-induced glia activation. Additionally, BCP inhibited the levels of inflammatory cytokines in the nigrostriatal system. The observed neuroprotection and inhibited glia activation were reversed upon treatment with the CB2R selective antagonist AM630, confirming the involvement of the CB2R. These results indicate that BCP acts via multiple neuroprotective mechanisms in our murine model and suggest that BCP may be viewed as a potential treatment and/or preventative agent for PD.

9.
Endocrinol Diabetes Nutr ; 64(1): 11-17, 2017 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28440765

RESUMO

OBJECTIVE: The theory of fetal programming suggests that low birth weight (LBW) predisposes to greater food intake and increases the chance of overweight and obesity, which are in turn associated to conditions such as metabolic syndrome (MS) and acanthosis nigricans. The study objective was to ascertain whether an association exists between MS, LBW, intake of high-calorie diets, and acanthosis nigricans in children and adolescents with overweight or obesity. MATERIAL AND METHODS: A case-control was conducted on 100 children who attended the overweight and obesity outpatient clinic of the OPD Hospital Civil de Guadalajara "Fray Antonio Alcalde". Subjects were stratified in groups with and without MS based on the criteria of the International Diabetes Federation for children aged less than 16 years. Data on LBW, intake of high-calorie diets for 24-hour dietary recalls (average 2 days a week), and acanthosis nigricans (Simone criteria) were obtained by questioning the parents. Frequencies and logistic regression were calculated using SPSS version 22. RESULTS: The results show that 82% of children and adolescents were obese and 18% overweight, and 73% had MS. MS was associated to LBW (OR: 4.83 [95% CI: 1.9-12.47]), high-calorie diets (OR:136.8 [95% CI: 7.7-2434]), and acanthosis nigricans (OR: 1872 [95% CI: 112.9-31028]). CONCLUSIONS: In children and adolescents with overweight and obesity, LBW, high-calorie diets, and acanthosis nigricans are associated to a higher probability of MS.


Assuntos
Acantose Nigricans/epidemiologia , Síndrome Metabólica/epidemiologia , Sobrepeso/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Acantose Nigricans/etiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Dieta , Registros de Dieta , Suscetibilidade a Doenças , Escolaridade , Ingestão de Energia , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Síndrome Metabólica/etiologia , México/epidemiologia , Obesidade/epidemiologia , Obesidade/etiologia , Sobrepeso/etiologia , Gravidez , Prevalência
10.
J Immunol Res ; 2017: 1548905, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29359168

RESUMO

The serine incorporator 5 (SERINC5) is a recently discovered restriction factor that inhibits viral infectivity by preventing fusion. Retroviruses have developed strategies to counteract the action of SERINC5, such as the expression of proteins like negative regulatory factor (Nef), S2, and glycosylated Gag (glycoGag). These accessory proteins downregulate SERINC5 from the plasma membrane for subsequent degradation in the lysosomes. The observed variability in the action of SERINC5 suggests the participation of other elements like the envelope glycoprotein (Env) that modulates susceptibility of the virus towards SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet been determined, although it has been proposed that it increases the sensitivity of the Env by exposing regions which are recognized by neutralizing antibodies. More studies are needed to understand the role of SERINC5 and to assess its utility as a therapeutic strategy.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Proteínas de Membrana/metabolismo , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo , Animais , Anticorpos Neutralizantes/metabolismo , Produtos do Gene gag/metabolismo , Anticorpos Anti-HIV/metabolismo , Infecções por HIV/imunologia , HIV-1/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Terapia de Alvo Molecular , Virulência , Internalização do Vírus , Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo
11.
AIDS Res Hum Retroviruses ; 32(12): 1219-1222, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27353350

RESUMO

The aim of this study was to compare the extent of resistance to antiretroviral (ARV) drugs among the population in Mexico before and after 2005. The mutations and drug resistance database of Stanford University were used for analyzing drug resistance tests that had been performed on HIV treatment-naive patients. The sequences obtained were divided into group 1 (isolated in 2002-2003) and group 2 (isolated in 2010-2014). Both groups showed 14% similarity in resistance mutations. In both groups, mutations in N88D protease inhibitor were identified, D67N and T69D were found for nucleoside reverse transcriptase inhibitors (NRTIs), and K103N was found for non-nucleoside reverse transcriptase inhibitors. In both groups, the resistance to ARV drugs was 7.4%. Both groups showed resistance to nelfinavir, efavirenz, and nevirapine. The prevalence of resistance to ARV therapy remained stable from 2002 to 2014. However, a marked reduction in resistance to NRTIs was observed for the same period.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Infecções por HIV/virologia , HIV/efeitos dos fármacos , Bases de Dados Genéticas , Feminino , Técnicas de Genotipagem , HIV/genética , Humanos , Masculino , México , Mutação de Sentido Incorreto
12.
PLoS One ; 11(3): e0151637, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27015634

RESUMO

HIV-seropositive patients show high incidence of coronary heart disease and oxidative stress has been described as relevant key in atherosclerosis development. The aim of this study was to assess the effect of omega 3 fatty acids on different markers of oxidative stress in HIV-seropositive patients. We performed a randomized parallel controlled clinical trial in The Instituto Mexicano del Seguro Social, a public health hospital. 70 HIV-seropositive patients aged 20 to 55 on clinical score A1, A2, B1 or B2 receiving highly active antiretroviral therapy (HAART) were studied. They were randomly assigned to receive omega 3 fatty acids 2.4 g (Zonelabs, Marblehead MA) or placebo for 6 months. At baseline and at the end of the study, anthropometric measurements, lipid profile, glucose and stress oxidative levels [nitric oxide catabolites, lipoperoxides (malondialdehyde plus 4-hydroxialkenals), and glutathione] were evaluated. Principal HAART therapy was EFV/TDF/FTC (55%) and AZT/3TC/EFV (15%) without difference between groups. Treatment with omega 3 fatty acids as compared with placebo decreased triglycerides (-0.32 vs. 0.54 mmol/L; p = 0.04), but oxidative stress markers were not different between groups.


Assuntos
Terapia Antirretroviral de Alta Atividade , Ácidos Graxos Ômega-3/administração & dosagem , Infecções por HIV/dietoterapia , Estresse Oxidativo/efeitos dos fármacos , Adulto , Colesterol/metabolismo , Feminino , Glutationa/metabolismo , HIV/efeitos dos fármacos , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Carga Viral/efeitos dos fármacos
13.
Rev. chil. nutr ; 42(4): 369-373, dic. 2015. tab
Artigo em Inglês | LILACS | ID: lil-775508

RESUMO

Objective: The aim of this study was to compare the risk of Eating Disorders Behaviour (EDB), and its anthropometric profile, physical activity and alimentary intake between Mexican fashion models (FM) and control women Methods: We included 50 FM and 50 control women, of the same social group, all over 18 years old, from Guadalajara, Mexico, matched by age. We evaluated the risk of EDB with the Eating Attitudes Test (EAT-26); the anthropometric measures were taken according to the criteria of the International Society for the Advancement of Kinanthropometry (ISAK), 24-hour recall to estimate energy intake and physical activities. Results: The risk prevalence of EDB was 10% for both groups. The mean and standard deviation of the percentage of body fat in FM was 22,4±2, lower than in the controls (27,8±4, p<0.001). There were no differences in anthropometric measurements in women with and without risk of EDB, except in the weight (FM without risk of EDB 56,3±3 kg and 59,9±3 kg with risk of EDB (p<0.02). Caloric intake in women with risk of EDB reduced was 1094±208 kcal in FM versus 1269±435 kcal in control woman. Conclusion: The anthropometric measurements, alimentary intake and previous history of eating disorders, suggests that FM of Mexico are a vulnerable population for eating disorder.


Objetivo: Comparar el riesgo de trastornos de la conducta alimentaria (TCA), perfil antropométrico, actividad física e ingesta alimentaria entre las mujeres mexicanas dedicadas al modelaje profesional (MP) con mujeres control. Métodos: Se incluyeron 50 MP y 50 mujeres controles, del mismo grupo social, mayores de 18 años, de Guadalajara, México, pareadas por edad. Se evaluó el riesgo de TCA con el test de Trastornos de Actitudes Alimentarias (EAT-26), se tomaron las medidas antropométricas de acuerdo a los criterios de la International Society for the Advancement of Kinanthropometry (ISAK). Se estimó el consumo de energía utilizando el recordatorio de 24 horas y se registró la práctica de actividades físicas. Resultados: La prevalencia de riesgo de TCA fue 10% para ambos grupos. La media y desviación estándar del porcentaje de grasa corporal en las MP fue 22,4±2,5 menor al de las controles (27,8±4,9) (p<0.001). No hubo diferencias en la medidas antropométricas en las mujeres con y sin riesgo de TCA, excepto en el peso de las MP de 56,3±3,1 kg sin riesgo de TCA y 59,9±3,6 en las con riesgo de TCA (p<0.02). La ingesta alimentaria se encontró reducida en las mujeres con riesgo de TCA con respecto a las sin riesgo, con 1094,2±208,3 kcal versus 1269,8±435,0 kcal en las MP y controles respectivamente. Conclusión: Las medidas antropométricas, la ingesta alimentaria y la historia previa de trastornos de la alimentación, sugiere que la MP de México es una población vulnerable para trastornos de la alimentación.


Assuntos
Humanos , Mulheres Trabalhadoras , Ingestão de Energia , Anorexia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Índice de Massa Corporal , Bulimia Nervosa , Estado Nutricional , Medição de Risco
14.
Mutagenesis ; 29(6): 427-31, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25232046

RESUMO

The aim of this study is to assess the frequency of micronucleated cell (MNC) and nuclear abnormalities (NA) in the buccal mucosa cells of females with anorexia nervosa (AN) or bulimia nervosa (BN), compared with healthy women. Individuals with AN and BN have inadequate feeding and compensatory behaviour to avoid weight gain. These behaviours can cause extreme body stress, thereby inducing DNA damage. In a cross-sectional study, we assessed the frequency of MNC and NA in the buccal mucosa cells of female participants with AN or BN. All of these patients had been admitted to a private clinic for the treatment of eating disorders after diagnosis with AN (n = 10) or BN (n = 7) according to the DSM-IV. Age-matched healthy female participants (n = 17) composed the control group. Oral mucosa samples were collected, fixed, stained by aceto-orcein/fast green and microscopically examined. Normal cells, MNC and NAs were counted within a 2000 cell sample. The results were analyzed with the Kruskal-Wallis and Mann-Whitney tests. Differences were observed in the frequency of MNC in healthy females (1.2±0.9) versus that of patients with AN (3.4±1.5) (P < 0.0001) and BN (4.1±2.2) (P < 0.001). No differences were found among these groups in terms of NA. AN and BN are related to the loss of genetic material through chromosomal fractures and/or damage to the mitotic spindle (i.e. possibly a result of a deficiency in DNA precursors). Self-imposed compensatory behaviours in AN and BN, such as severe food restriction, potential malnutrition, vomiting, use of diuretics and laxatives and acute exhaustive exercise, are possible inducers of MNC and genotoxic damage. Of these compensatory behaviours, only vomiting has not been linked to genotoxic damage. This is the first report in women with BN, which should be studied in the future.


Assuntos
Anorexia Nervosa/patologia , Bulimia Nervosa/patologia , Micronúcleos com Defeito Cromossômico , Mucosa Bucal/patologia , Adolescente , Adulto , Antropometria , Estudos de Casos e Controles , Feminino , Humanos , Adulto Jovem
15.
Biomed Res Int ; 2014: 851820, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24977162

RESUMO

The use of raltegravir in treating HIV/AIDS has been proposed due to its effectiveness in suppressing high loads of HIV RNA in pregnant women, thus preventing infection of the fetus. However, administration of raltegravir during pregnancy produces a compound which is transferred to high concentrations to the offspring. The objective of this study is to evaluate the transplacental genotoxic effect of raltegravir in newborn rats. We evaluated the number of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) in the peripheral blood samples of the offspring of Wistar rats treated 6 days before birth with oral administration of raltegravir. The animals were randomly assigned to five groups as follows: raltegravir at doses of 15, 30, or 60 mg/day, cyclophosphamide 10 mg/kg (positive control), or 0.5 ml of sterile water (negative control). In addition, the effect of these drugs on the weight and height of newborns was assessed. There were no differences in the number of MNE, MNPCE, and PCE, and a slight decrease in the weight and height was observed in the offspring of the rat mothers treated with raltegravir. Genotoxicity studies are required in pregnant women to determine the risk of using raltegravir to the fetuses.


Assuntos
Eritrócitos/efeitos dos fármacos , Eritrócitos/fisiologia , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Pirrolidinonas/administração & dosagem , Pirrolidinonas/toxicidade , Administração Oral , Animais , Animais Recém-Nascidos , Antivirais/administração & dosagem , Antivirais/farmacocinética , Antivirais/toxicidade , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Placenta/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Pirrolidinonas/farmacocinética , Raltegravir Potássico , Ratos , Ratos Wistar
16.
BMC Bioinformatics ; 15: 72, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24629078

RESUMO

BACKGROUND: The correlations of genotypic and phenotypic tests with treatment, clinical history and the significance of mutations in viruses of HIV-infected patients are used to establish resistance mutations to protease inhibitors (PIs). Emerging mutations in human immunodeficiency virus type 1 (HIV-1) protease confer resistance to PIs by inducing structural changes at the ligand interaction site. The aim of this study was to establish an in silico structural relationship between natural HIV-1 polymorphisms and unusual HIV-1 mutations that confer resistance to PIs. RESULTS: Protease sequences isolated from 151 Mexican HIV-1 patients that were naïve to, or subjected to antiretroviral therapy, were examined. We identified 41 unrelated resistance mutations with a prevalence greater than 1%. Among these mutations, nine exhibited positive selection, three were natural polymorphisms (L63S/V/H) in a codon associated with drug resistance, and six were unusual mutations (L5F, D29V, L63R/G, P79L and T91V). The D29V mutation, with a prevalence of 1.32% in the studied population, was only found in patients treated with antiretroviral drugs. Using in silico modelling, we observed that D29V formed unstable protease complexes when were docked with lopinavir, saquinavir, darunavir, tipranavir, indinavir and atazanavir. CONCLUSIONS: The structural correlation of natural polymorphisms and unusual mutations with drug resistance is useful for the identification of HIV-1 variants with potential resistance to PIs. The D29V mutation likely confers a selection advantage in viruses; however, in silico, presence of this mutation results in unstable enzyme/PI complexes, that possibly induce resistance to PIs.


Assuntos
Farmacorresistência Viral/genética , Inibidores da Protease de HIV/farmacologia , Protease de HIV/genética , HIV-1/enzimologia , HIV-1/genética , Sulfato de Atazanavir , Sequência de Bases , Darunavir , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Protease de HIV/química , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Humanos , Masculino , Simulação de Acoplamento Molecular , Dados de Sequência Molecular , Mutação , Oligopeptídeos/farmacologia , Oligopeptídeos/uso terapêutico , Fenótipo , Polimorfismo Genético , Piridinas/farmacologia , Piridinas/uso terapêutico , Pironas/farmacologia , Pironas/uso terapêutico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico
17.
Brain Res ; 1470: 1-10, 2012 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-22750586

RESUMO

Cognitive impairment or its recovery has been associated with the absence or reestablishment of estrogenic actions in the central nervous system of female experimental animals or women. It has been proposed that these cognitive phenomena are related to estrogen-mediated modulatory activity of synaptic transmission in brain structures involved in cognitive functions. In the present work a morphological study was conducted in adult female ovariectomized rats to evaluate estradiol-dependent dendritic spine sprouting in hippocampal pyramidal neurons, and changes in the presynaptic marker synaptophysin. Three or ten days after estradiol treatment (10 µg/day, twice) in the ovariectomized rats, a significant increase of synaptophysin was observed, which was coincident with a significant higher numerical density of thin (22%), stubby (36%), mushroom (47%) and double spines (125%), at day 3, without significant changes of spine density at day 10, after treatment. These results may be interpreted as evidence of pre- and postsynaptic plastic events that may be involved in the modulation of cognitive-related behavioral performance after estrogen replacement therapy.


Assuntos
Região CA1 Hipocampal/citologia , Espinhas Dendríticas/efeitos dos fármacos , Estradiol/farmacologia , Estrogênios/farmacologia , Células Piramidais/ultraestrutura , Análise de Variância , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Ovariectomia , Células Piramidais/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Coloração pela Prata , Sinaptofisina/metabolismo
18.
AIDS Res Hum Retroviruses ; 26(7): 777-81, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20624071

RESUMO

The molecular epidemiology of subtypes and intersubtype recombinants (IRs) of human immunodeficiency virus type 1 (HIV-1) in Mexico has not been characterized fully. Understanding its regional distribution, prevalence, adaptability, viral fitness, pathogenicity, and immunogenicity is decisive for any design of an effective HIV vaccine. The aim of this study was to describe the presence of IRs types BG and BF in a Mexican population. Protease and reverse transcriptase regions of the pol gene were sequenced using an automated sequencing system. A phylogenic tree was constructed and genetic distances were calculated using MEGA 3.1. Recombination analysis was done by bootscan using SimPlot software. Two hundred and twenty-three HIV-1-positive individuals were enrolled in the study. At baseline, the mean plasma viral load was 285,500 HIV-1 RNA copies/ml and the mean CD4 cell count was 213 cells/ml. Subtype B was found in 220 (98.6%) samples, whereas IRs were found in three patients (1.4%): two (0.9%) with BG and one (0.45%) with BF. IRs were observed in 2/124 (1.6%) samples from treated patients and in 1/99 (1.0%) from naive patients. The presence of these HIV forms at low frequency points to the need for research on the diversity, geographic distribution, and evolution of other subtypes including circulating recombinant forms and IRs to understand the molecular epidemiology and tendencies of the HIV infection in Mexico.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Feminino , Genótipo , HIV-1/isolamento & purificação , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , Recombinação Genética , Análise de Sequência de DNA , Homologia de Sequência
19.
Rheumatol Int ; 29(10): 1169-75, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19112564

RESUMO

The depressive symptoms are associated with chronic pain in this study. A cross-sectional study was performed. A visual analog scale was used to register pain intensity. Depressive symptoms were measured using the Center of Epidemiological Studies (CES-Dr) scale as modified by Eaton and reviewed for use in the Mexican population. The study included 245 patients, with a mean age of 46 years, 86.1% of whom were female. The prevalence of some degree of depression was 55.1%. Patients with fibromyalgia had the highest prevalence of symptoms of depression (78.38%) and major depression (29.73%). Stepwise multiple regressions indicated that the best model (r2 = 0.26) to predict the CES-Dr score included the global pain score (P < 0.0001) and education level (P < 0.004). The Cronbach's alpha of the CES-Dr was high (alpha = 0.888). There was moderate correlation (r = 0.442), P < 0.0001 of the CES-Dr numeric score with the intensity of global pain.


Assuntos
Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Hospitais de Ensino , Dor , Reumatologia , Estudos Transversais , Feminino , Humanos , Entrevistas como Assunto , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Prevalência , Escalas de Graduação Psiquiátrica , População Rural , População Urbana
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