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(1) Background: Evidence regarding Non-Alcoholic Fatty Liver Disease (NAFLD) diagnosis is limited in the context of patients with gallstone disease (GD). This study aimed to assess the predictive potential of conventional clinical and biochemical variables as combined models for diagnosing NAFLD in patients with GD. (2) Methods: A cross-sectional study including 239 patients with GD and NAFLD diagnosed by ultrasonography who underwent laparoscopic cholecystectomy and liver biopsy was conducted. Previous clinical indices were also determined. Predictive models for the presence of NAFLD stratified by biological sex were obtained through binary logistic regression and sensitivity analyses were performed. (3) Results: For women, the model included total cholesterol (TC), age and alanine aminotransferase (ALT) and showed an area under receiver operating characteristic curve (AUC) of 0.727 (p < 0.001), sensitivity of 0.831 and a specificity of 0.517. For men, the model included TC, body mass index (BMI) and aspartate aminotransferase (AST), had an AUC of 0.898 (p < 0.001), sensitivity of 0.917 and specificity of 0.818. In both sexes, the diagnostic performance of the designed equations was superior to the previous indices. (4) Conclusions: These models have the potential to offer valuable guidance to healthcare providers in clinical decision-making, enabling them to achieve optimal outcomes for each patient.
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This study recorded the use of medicinal plants in the rural communities from the municipality of Dolores Hidalgo, Guanajuato, Mexico. Data were obtained through open semi-structured interviews with local respondents (n=181), and medicinal plants were recorded and identified in herbariums. The Relative importance (RI) and Informant Consensus Factor (ICF) were calculated to analyze the survey data. In total, 68 plant species belonging to 33 families were reported. Asteraceae had the highest number of species, representing 14. The highest RI was accounted by Chamaemelum nobile (RI=2.0), followed by Thymus vulgaris (RI=1.83),and Moringa oleifera (RI= 1.60). The highest ICF was reported by diseases associated with the respiratory (ICF=0.80), digestive (ICF=0.75), and musculoskeletal systems including connective tissues (ICF= 0.71). Respondents have knowledge about medicinal plant use for primary health care and other chronic diseases. The information obtained here could be extrapolated to different rural areas in Mexico.
Este estudio registró el uso de plantas medicinales en las comunidades rurales del municipio de Dolores Hidalgo, Guanajuato, México. Los datos se obtuvieron a través de entrevistas abiertas semiestructuradas con encuestados locales (n=181), y las plantas medicinales se registraron e identificaron en los herbarios. La importancia relativa (RI) y el factor de consenso del informante (ICF) se calcularon para analizar los datos de la encuesta. En total, se reportaron 68 especies de plantas pertenecientes a 33 familias. Asteraceae tuvo el mayor número de especies, representando 14. El RI más alto fue contabilizado por Chamaemelum nobile (RI = 2.0), seguido por Thymus vulgaris (RI = 1.83) y Moringa oleifera (RI = 1.60). La ICF más alta se informó por enfermedades asociadas con los sistemas respiratorio (ICF = 0,80), digestivo (ICF = 0,75) y musculoesquelético, incluidos los tejidos conectivos (ICF = 0,71). Los encuestados tienen conocimientos sobre el uso de plantas medicinales para la atención primaria de salud y otras enfermedades crónicas. La información aquí obtenida podría extrapolarse a diferentes zonas rurales de México.
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Plantas Medicinales , Medicina Tradicional , Población Rural , Encuestas y Cuestionarios , Etnobotánica , MéxicoRESUMEN
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic fat deposition in the liver. However, a recent classification of this condition, which also integrates the presence of coexisting metabolic disorders, termed Metabolic dysfunction Associated Fatty Liver Disease (MAFLD), has been proposed. NAFLD is increasingly common in early childhood, partly due to the increase in metabolic disease in this age. Thus, studying hepatic steatosis in the metabolic context has become important in this population as well. However, NAFLD, and thus MAFLD, diagnosis in children is challenging by the lack of non-invasive diagnostic tools comparable to the gold standard of hepatic biopsy. Recent studies have reported that the Pediatric Metabolic Index (PMI) could be a marker of insulin resistance and abnormal liver enzymes, but its association with NAFLD, MAFLD, or altered adipokines in these conditions has not been reported. The aim of this study is to evaluate the correlation between PMI with the diagnosis of NAFLD or MAFLD, together with serum levels of leptin and adiponectin, in school-age children. METHODS: A cross sectional study was carried out in two hundred and twenty-three children without medical history of hypothyroidism, genetic, or chronic diseases. Anthropometry, liver ultrasound, and serum levels of lipids, leptin, and adiponectin were evaluated. The children were classified as having NAFLD or non-NAFLD, and a subgroup of MAFLD in the NAFLD group was analyzed. The PMI was calculated by the established formulas for age and gender. RESULTS: PMI correlated positively with the presence and severity of NAFLD (r = 0.62, p<0.001 and r = 0.79, p<0.001 respectively) and with the presence of MAFLD (r = 0.62; p<0.001). Also, this index correlated positively with serum leptin levels (r = 0.66; p<0.001) and negatively with serum adiponectin levels (r= -0.65; p<0.001). PMI showed to be a good predictor for diagnosing NAFLD in school-age children when performing a ROC curve analysis (AUROC=0.986, p< 0.0001). CONCLUSION: PMI could be a useful tool for the early diagnosis of NAFLD or MAFLD in children. However, future studies are necessary to establish validated cut-off points for each population.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Niño , Preescolar , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Adipoquinas , Leptina , Adiponectina , Estudios Transversales , Índice de Masa CorporalRESUMEN
This study evaluated the prevalence of concomitant use of herbal products for weight loss (HPWL) and allopathic medicine. Factors associated with the prevalence, adverse reactions, and the alteration of medication adherence with the concomitant use of HPWL alone and in combination with allopathic medicine, were assessed. The study was descriptive and cross-sectional using a questionnaire conducted among people with overweight or obesity (n=662) from five cities of Central Mexico. Adherence to medications was measured using the Morisky Medication Adherence Scale. The prevalence of adverse reactions induced by the concomitant use of HPWL, and allopathic medicine was 25.3%. The use of HPWL affected medication adherence by 68%. There is a high prevalence (45.2%) of concomitant use of HPWL and allopathic medicine in people with overweight or obesity in Central Mexico. The concomitant use of HPWL and allopathic medicine induces adverse reactions, mainly gastrointestinal, and thus, medication adherence is affected.
Este estudio evaluó la prevalencia del uso concomitante de productos a base de hierbas para bajar de peso (HPWL) y medicina alopática. Se evaluaron los factores asociados con la prevalencia, las reacciones adversas y la alteración de la adherencia a la medicación con el uso concomitante de HPWL solo y en combinación con medicina alopática. El estudio fue descriptivo y transversal mediante un cuestionario realizado entre personas con sobrepeso u obesidad (n = 662) de cinco ciudades del centro de México. La adherencia a los medicamentos se midió mediante la Escala de adherencia a la medicación de Morisky. La prevalencia de reacciones adversas inducidas por el uso concomitante de HPWL y medicina alopática fue del 25,3%. El uso de HPWL afectó la adherencia a la medicación en un 68%. Existe una alta prevalencia (45.2%) de uso concomitante de HPWL y medicina alopática en personas con sobrepeso u obesidad en el centro de México. El uso concomitante de HPWL y medicina alopática induce reacciones adversas, principalmente gastrointestinales, y por tanto, afecta la adherencia a la medicación.
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Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Pérdida de Peso/efectos de los fármacos , Practicas Alopaticas , Medicina de Hierbas , Estudios Transversales , Encuestas y Cuestionarios , Terapia Combinada/métodos , Interacciones Farmacológicas , Sobrepeso/tratamiento farmacológico , Cumplimiento de la Medicación , Fitoterapia/efectos adversos , Medicina Tradicional , México , Obesidad/tratamiento farmacológicoRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is the main liver disease worldwide, and its prevalence in children and adolescents has been increasing in the past years. It has been demonstrated that parental exposure to different conditions, both preconceptionally and during pregnancy, can lead to fetal programming of several metabolic diseases, including NAFLD. In this article, we review some of the maternal and paternal conditions that may be involved in early-life programing of adult NAFLD. First, we describe the maternal nutritional factors that have been suggested to increase the risk of NAFLD in the offspring, such as an obesogenic diet, overweight/obesity, and altered lipogenesis. Second, we review the association of certain vitamin supplementation and the use of some drugs during pregnancy, for instance, glucocorticoids, with a higher risk of NAFLD. Furthermore, we discuss the evidence showing that maternal-fetal pathologies, including gestational diabetes mellitus (GDM), insulin resistance (IR), and intrauterine growth restriction (IUGR), as well as the exposure to environmental contaminants, and the impact of microbiome changes, are important factors in early-life programming of NAFLD. Finally, we review how paternal preconceptional conditions, such as exercise and diet (particularly obesogenic diets), may impact fetal growth and liver function. Altogether, the presented evidence supports the hypothesis that both in utero exposure and parental conditions may influence fetal outcomes, including the development of NAFLD in early life and adulthood. The study of these conditions is crucial to better understand the diverse mechanisms involved in NAFLD, as well as for defining new preventive strategies for this disease.
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Enfermedad del Hígado Graso no Alcohólico , Efectos Tardíos de la Exposición Prenatal , Embarazo , Niño , Femenino , Adolescente , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/metabolismo , Sobrepeso , Desarrollo Fetal , Retardo del Crecimiento Fetal , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/metabolismoRESUMEN
BACKGROUND: Pediatric self-medication is based on the subjective interpretation of symptoms in children by the mother or an adult, the decision to self-medicate is made by a third party. The objective of this work is to provide information on the factors and practices associated with the self-medication of children among parents in Mexico. METHODS: A cross-sectional and descriptive study was conducted between June 2020 and December 2021 on Mexican parents with children under 12 years of age. Online questionnaires were completed with sections on sociodemographic characteristics, use of medicines or medicinal plants and their treated symptoms, sources of collection, and their recommendation. RESULTS: A total of 9905 online surveys were completed with representation from the 32 states of Mexico, and the prevalence of self-medication was 49.6% (n = 4908). Associated factors were age, having two or more children, children with chronic illnesses, medium educational level, unemployment or employment unrelated to health, medium and high socioeconomic level, and lack of medical security. Respondents self-medicated their children on the recommendation of a family member or friend (55.8%), and own initiative (28%). The most used medication was VapoRub (61.3%), followed by paracetamol (56.9%) and chamomile (33.1%), and the most prevalent symptoms were flu/flow (47.7%) followed by cough (34.2%). The main reasons were perceiving symptoms as not serious (69.9%) and reusing medications (51.9%). CONCLUSIONS: There is a high prevalence of self-medication in children in Mexico, mainly associated with children with chronic diseases and families with three or more children.
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OBJECTIVE: This study aims to assess the prevalence of herbal medicine (HM) use and factors influencing HM usage including the identification of the main plants consumed by patients with type 2 diabetes mellitus (T2DM) in central-western Mexico. DESIGN: A total of 1862 patients with diabetes were surveyed in public and private hospitals in four states (Guanajuato, Jalisco, Michoacan, and San Luis Potosi) of the central-western region of Mexico. The chi-square test was used to assess associations between HM use and demographic characteristics, such as glucose levels, presence of complications and comorbidities, as well as the selected therapy to treat T2DM. RESULTS: The prevalence of HM use (59.2%) in patients with T2DM was mainly associated with education level (p = 0.001), time of diagnosis of T2DM (p = 0.004), presence of complications (p < 0.001) and comorbidities (p = 0.018) and the use of insulin (p < 0.001). These patients report a higher consumption of herbal medicine compared to those on glycemic control (p < 0.001). The most frequently used medicinal plants to treat T2DM were nopal (54.9%), moringa (26.7%), and aloe (22.1%). CONCLUSION: The prevalence of HM use to treat T2DM in west-central Mexico is high (59.2%) and its consumption is mostly carried out without the recommendation of a health professional (91.9%). The use of HM increases mainly when the patient uses insulin, during complications of the disease or in patients with an inadequate glycemic control.
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Diabetes Mellitus Tipo 2 , Plantas Medicinales , Adulto , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Medicina de Hierbas , Humanos , México/epidemiología , FitoterapiaRESUMEN
BACKGROUND: The aim of this study was to assess the frequency of allopathic and complementary medicine use for preventing the infection with SARS-CoV-2 in Mexico. A descriptive and cross-sectional study was conducted using an online questionnaire among general adult population (n = 16,724) of the 32 Mexican states from March to November 2020. METHODS: The factors associated with the use, self-medication practice, and adverse reactions due the consumption of allopathic and complementary medicine to prevent infection with SARS-CoV-2 virus were assessed using a structured questionnaire. The suspected adverse reactions associated with the use of drugs or complementary medicine were reported. RESULTS: The prevalence (42.9%) of allopathic and/or complementary medicine use for preventing SARS-CoV-2 infection was mainly associated with unemployment [OR:2.026 (1.722-2.283)]. Acetaminophen (n = 2272) and vitamin C (n = 3252) were the main allopathic and complementary medicine products used to prevent SARS-CoV-2 infection, respectively. The prevalence of self-medication and adverse reactions was 35.3% and 4.8%, respectively. Self-medication [OR:1.930 (1.633-2.282)] and adverse reactions [OR:2.603 (2.015-3.363)] were mainly associated with individuals of low socioeconomic status. Hydroxychloroquine (21.2%) and chloroquine (15.2%) showed the highest prevalence of adverse reactions, which were mainly related to gastrointestinal disorders. CONCLUSION: The use of medications and complementary medicine to prevent SARS-CoV-2 infection is prevalent (almost one-half of the respondents) among Mexican population, and it is mainly associated with unemployment. Self-medication and the adverse reactions derived from self-medication are also prevalent and seem to be influenced by low socioeconomic status.
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ETHNOPHARMACOLOGICAL RELEVANCE: There are plant species used in the Mexican traditional medicine for the empirical treatment of anxiety and depression. AIM OF THE STUDY: This work assessed the prevalence of self-medication with medicinal plants and the prevalence of the concomitant use of prescribed psychiatric drugs and medicinal plants for treating symptoms associated with anxiety and depression during the Covid-19 lockdown in Mexico. MATERIALS AND METHODS: The suspected adverse reactions associated with drug-herb interactions were assessed. The factors associated with self-medication, the concomitant use of herb-drug combinations, and the presence of adverse reactions due their combined use is also reported. The study was descriptive and cross-sectional using an online questionnaire conducted among population with symptoms associated with anxiety and depression (n = 2100) from seven states of central-western Mexico. RESULTS: The prevalence of the use of herbs (61.9%) and the concomitant use of drug-herb combinations (25.3%) were associated with being diagnosed with mental illness [OR:2.195 (1.655-2.912)] and the use of psychiatric medications [OR:307.994 (178.609-531.107)], respectively. The presence of adverse reactions (n = 104) by the concomitant use of drug-herb combinations was associated with being unemployed [p = 0.004, OR: 3.017 (1.404-6.486)]. CONCLUSION: Health professionals should be aware if their patients concomitantly use medicinal plants and psychiatric drugs. Public health campaigns should promote the possible adverse reactions that might produce the concomitant use of drug-herb combinations for mental illnesses.
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Ansiedad/tratamiento farmacológico , COVID-19/psicología , Depresión/tratamiento farmacológico , Pandemias , Preparaciones de Plantas/efectos adversos , Preparaciones de Plantas/uso terapéutico , Adolescente , Adulto , Anciano , Control de Enfermedades Transmisibles , Estudios Transversales , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/psicología , México/epidemiología , Persona de Mediana Edad , Plantas Medicinales , Prevalencia , Psicotrópicos/efectos adversos , Psicotrópicos/uso terapéutico , Autocuidado , Encuestas y Cuestionarios , Desempleo/psicología , Adulto JovenRESUMEN
INTRODUCTION AND OBJECTIVE: Non-Alcoholic Fatty Liver Disease (NAFLD) is a metabolic liver disease related to insulin resistance, which requires invasive methods for diagnosis. The aim of this study was to analyze whether the use of an algorithm involving both clinical indices and hepatic ultrasound measurements improves the accuracy for the non-invasive diagnosis of NAFLD. PATIENTS AND METHODS: Cross-sectional study with patients undergoing elective cholecystectomy. We collected anthropometric, metabolic, liver biopsy, and liver ultrasonography data. We calculated unpaired t-test and Pearson's coefficient, and areas under the receiver-operating characteristic curves (AUROC) for the Fatty Liver Index (FLI), Lipid Accumulation Product (LAP) indexes, right liver index diameter, and for predictive models constructed with discriminant analysis. RESULTS: One hundred patients in groups with and without NAFLD. FLI, LAP, right and caudate liver lobe diameters, and congestion index were higher in NAFLD group (pâ¯=â¯0.011, pâ¯=â¯0.011, pâ¯=â¯0.001, pâ¯=â¯0.027, pâ¯=â¯0.009). The right liver lobe diameter had the highest AUROC. Predictive models that combined sensitivity and specificity for the clinical indexes and liver ultrasound had an AUROC over 0.7. CONCLUSION: The ultrasonography measure of right liver lobe diameter by itself can reliably identify patients with NAFLD with a good sensitivity and specificity, however, this can be improved by adding the LAP mathematical index in our population.
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Algoritmos , Hígado/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Ultrasonografía/métodos , Adulto , Estudios Transversales , Femenino , Humanos , Pruebas de Función Hepática , Masculino , Curva ROCRESUMEN
Background Fibroblast growth factor 21 (FGF21) is considered an important regulator of lipid and glucose metabolism. However, the role of FGF21 in macronutrient intake and metabolic disease, particularly in pediatric population, still needs further clarification. This study aimed to evaluate the association of rs11665896 in the FGF21 gene with metabolic status and macronutrient intake in a cohort of Mexican children with obesity. Methods Eighty-four lean children and 113 children with obesity, from 8 to 11 years of age, were recruited. FGF21 rs11665896 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Somatometric evaluations, nutrient intake, glucose, lipids, insulin and FGF21 serum levels were measured in the obesity group. Results The T allele of rs11665896 in the FGF21 gene was associated with obesity (odds ratio [OR] = 1.99, 95% confidence interval [CI] = 1.14-3.46; p = 0.0151). Subjects with obesity carrying the TT genotype consumed less lipids and more carbohydrates compared to other genotypes. Circulating FGF21 levels correlated negatively with carbohydrate intake (r = -0.232, p = 0.022) and positively with body weight (r = 0.269, p = 0.007), waist (r = 0.242, p = 0.016) and hip girth (r = 0.204, p = 0.042). FGF21 levels were lower in carriers of at least one T allele. Conclusions Genetic variants in FGF21 could influence metabolic status, food preferences and qualitative changes in nutritional behavior in children.
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Regiones no Traducidas 3'/genética , Factores de Crecimiento de Fibroblastos/genética , Nutrientes/metabolismo , Obesidad/genética , Obesidad/patología , Polimorfismo Genético , Biomarcadores/análisis , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Estudios Transversales , Ingestión de Energía , Femenino , Estudios de Seguimiento , Humanos , Resistencia a la Insulina , Lípidos , Masculino , Obesidad/metabolismo , PronósticoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Mexico ranks second in the world for obesity prevalence. In Mexico, obese and overweight subjects commonly seek alternative treatments for weight-loss, including the use of herbal products. AIM OF THE STUDY: The main objective of this study was to evaluate the prevalence of self-medication with herbal products for weight-loss among overweight and obese subjects residing in four states (Guanajuato, San Luis Potosi, State of Mexico, and Mexico City) from central Mexico. In addition, the factors related to self-medication among patients were studied. MATERIALS AND METHODS: A total of 1404 overweight and obese subjects were interviewed. A chi-square test examined associations between socio-demographic and socio-economic information, and self-medication with herbal products for weight-loss. RESULTS: The prevalence of self-medication was 42.9% among the participants who used herbal products for weight-loss. The female gender was the strongest factor (OR: 2.20 (1.75-2.77) associated with self-medication for weight-loss, followed by a low educational level (elementary and middle school) [OR: 1.80 (1.31-2.44)], and a middle-socioeconomic status [OR: 1.75 (1.21-2.52)]. The main herbal products used for weight-loss were based on: i) green tea, Camellia sinensis (12.7% of frequency), ii) aceitilla, Bidens odorata (6.6%), and iii) soybean, Glycine max (5.3%). In addition, 65% of the respondents considered herbal products ineffective for weight-loss after 6 months of use. CONCLUSION: Due to the high incidence of overweight and obesity in Mexico, there is a high prevalence (42.9%) of self-medication using natural products for weight-loss, particularly in women from Central Mexico. This study indicates the important need to educate patients about the harmful effects of consuming these products.
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Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Preparaciones de Plantas/uso terapéutico , Automedicación/estadística & datos numéricos , Adulto , Femenino , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Plantas Medicinales/química , Prevalencia , Factores Sexuales , Factores Socioeconómicos , Pérdida de Peso/efectos de los fármacos , Adulto JovenRESUMEN
Self-medication during pregnancy represents a serious threat for mother and child health. The objective of this study was to evaluate the prevalence and the factors associated with self-medication among Mexican women living in the central region of Mexico. This is a descriptive interview-study of 1798 pregnant women or women who were pregnant no more than 3â¯years ago, when the interview was carried out. Data analysis was carried out with chi-square analysis and odds ratio. The prevalence of self-medication (allopathic drugs, medicinal plants, and other products, including vitamins, food supplements, among others) was 21.9%. The factors associated (pâ¯<â¯0.05) with self-medication were: higher education (college and postgraduate), smoking, and consumption of alcohol. Smoking was the strongest factor (OR: 2.536; 1.46-4.42) associated to self-medication during pregnancy, followed by consumption of alcohol (OR: 2.06; 1.38-3.08), and higher education (OR: 1.607; 1.18-2.19). Medicinal plant consumption was associated with nausea, constipation, migraine, and cold (pâ¯<â¯0.05), whereas he self-medication of allopathy was associated with gastritis and migraine (pâ¯<â¯0.05). Self-medication was influenced mainly by a relative or friend, who recommended the use of herbal medicine/allopathic medication. Two of the most common medicinal plants (arnica and ruda) here informed are reported to induce abortion or toxicity during pregnancy. The findings showed that self-medication (medicinal plants and allopathic medication) is a common practice among pregnant women from central Mexico. Adequate counselling of pregnant women by healthcare professionals about the potential risks of self-medication with herbal medicine and allopathic drugs during pregnancy is strongly warranted.
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BACKGROUND AND OBJECTIVES: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. MATERIAL AND METHODS: A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. RESULTS: We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05). CONCLUSION: The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies.
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Anticuerpos Antiproteína Citrulinada/sangre , Artritis Reumatoide/genética , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Adulto , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Técnicas de Genotipaje , Homocigoto , Humanos , Masculino , México , Persona de Mediana Edad , Factores ProtectoresRESUMEN
Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP), a consequence of the breakdown of immune tolerance. The lymphoid tyrosine phosphatase (Lyp) protein has significant effects on maintenance of peripheral immune tolerance. Two polymorphic variants (-1123G>C and +1858C>T) at PTPN22 gene that encodes this protein have been associated with autoimmune disorders and found in strong linkage disequilibrium in Caucasian population. We evaluated whether PTPN22 haplotypes (-1123G>C/+1858C>T) are associated with anti-CCP antibodies, as well as susceptibility to RA in a Western Mexican population. A total of 315 RA patients and 315 control subjects (CS) were included. The polymorphisms were genotyped by PCR-RFLP and the anti-CCP antibodies were determined by ELISA. The PTPN22 polymorphisms were in strong linkage disequilibrium (D' = 1.00 in CS). The susceptibility haplotype CT was significantly more frequent in RA patients than in CS (OR 2.18, 95% CI 1.15-4.16, p = 0.01). No association between haplotypes and anti-CCP antibodies levels was observed. In conclusion, this study confirmed that -1123G>C and +1858C>T PTPN22 polymorphisms are in strong linkage disequilibrium and the CT haplotype is a susceptibility marker to RA in Western Mexico. However, the PTPN22 haplotypes are not associated with anti-CCP antibodies.
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Peptidyl arginine deiminase IV (PADI4) enzyme catalyzes the citrullination of proteins, which are recognized by anti-cyclic citrullinated peptide antibodies (anti-CCP) in rheumatoid arthritis (RA) patients. Here, we determined the association between PADI4 gene polymorphisms and haplotypes with RA susceptibility and clinical characteristics in a western Mexican population. The relationship of PADI4 polymorphisms with anti-CCP and PADI4 mRNA expression was also evaluated. PADI4_89, PADI4_90 and PADI4_92 polymorphisms were individually associated with RA susceptibility. The GTG haplotype was significantly associated with: RA susceptibility; disease onset at ≤ 40 years and anti-CCP antibodies. PADI4 expression was three fold higher in RA patients carrying the susceptibility haplotype (GTG) than in non-susceptibility haplotype carriers (ACC). In conclusion, polymorphisms and functional haplotype (GTG) in PADI4 are associated with RA susceptibility as well as anti-CCP antibodies in a Mexican population. This supports the role of PADI4 early in RA pathogenesis by promoting the generation of citrullinated autoantigens.
Asunto(s)
Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad/genética , Haplotipos , Hidrolasas/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Alelos , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Femenino , Regulación Enzimológica de la Expresión Génica , Frecuencia de los Genes , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , México , Persona de Mediana Edad , Péptidos Cíclicos/inmunología , Arginina Deiminasa Proteína-Tipo 4 , Desiminasas de la Arginina Proteica , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
INTRODUCTION: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The PTPN22 gene encodes lymphoid tyrosine phosphatase LYP, a potent negative regulator of T cell activation. Polymorphic variants of this gene have previously been associated with various autoimmune disorders. The +1858C/T single-nucleotide polymorphism (SNP) (rs2476601), in the exon 14 of the PTPN22 gene has been associated with susceptibility to RA in several population. OBJECTIVE: The aim of this work was to investigate whether the +1858C/T of the PTPN22 gene is associated with susceptibility to RA in Western Mexico population. METHODS: A total of 309 unrelated RA patients, classified according to American College of Rheumatology (ACR) 1987 criteria, as well as 347 controls residents from Western Mexico were recruited for this study. The DNA samples were genotyped for +1858C/T PTPN22 gene SNP using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The frequency of +1858T risk allele was significantly increased in patients with RA compared with controls (p=0.001, OR=2.83, 95%CI=1.50-5.32). To confirm this results we established a comparison between subjects carrying of CT+TT genotypes versus those carrying CC genotype, between both groups (p=0.004, OR=2.65, 95%CI=1.33-5.36). Nevertheless, we not observed association of the +1858C/T PTPN22 gene SNP with clinical activity and functional disability in RA patients. Likewise, the +1858T variant in RA patients seropositive for anti-CCP antibodies, increased the risk for RA (p=0.008, OR=2.5, 95%CI=1.3-5.0) when we compared with controls; however, in the group of seronegative patients, no was found significant difference (p=0.1, OR=2.5, 95%CI=0.9-7.2). CONCLUSIONS: Our results support the association of the +1858T risk allele of the +1858C/T PTPN22 polymorphism with susceptibility to RA and confirm that, in combination with anti-CCP antibodies, this SNP influence the autoimmune processes towards a development of RA in Mexican population.