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Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1-patients with sepsis treated with conventional treatment without vitamin C; Group 2-patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31-0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.
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Ácido Ascórbico , Sepse , Humanos , Ácido Ascórbico/uso terapêutico , Estudos Prospectivos , Escores de Disfunção Orgânica , Sepse/diagnóstico , Unidades de Terapia Intensiva , VitaminasRESUMO
The objective of the study is to determine the personal, behavioral and psychological variables associated with somatization and the number of diseases in each gender from a sample of Mexican general population. They answered a questionnaire of behavioral and psychological variables including somatization and the sum of 16 different diseases and any additional one, finally the body mass index (BMI) was measured. A total of 164 participants (women = 90, men = 74) were included. We observed that women had more somatization and number of diseases than men and that more variables (mainly psychological) were associated with somatization and with the number of diseases in women than in men. Among the variables most negatively correlated in women with both variables were sleep quality (r = -0.525 and r = -0.536, p < 0.001), self-acceptance (r = -0.460 and r = -0.501, p < 0.001), positive relations with others (r = -0.447 and r = -0.441 p < 0.001), environmental mastery (r = -0.414, p < 0.001, for both variables), purpose in life and optimism; while men only showed a low negative correlation between emotion regulation and the number of diseases (r = -0.289, p < 0.05). The positive associated variables in women were anxiety, negative emotions and depression; while men showed a lower correlation between these three variables only with somatization. The somatization and age were positively related to the number of diseases in both genders and the BMI was significantly associated with the number of diseases only in men. In conclusion, women had more somatization and number of diseases than men and also had more relation between psychological variables and the two dependent variables than men, which could in part explains the higher values of somatization and the number of diseases in women, considering that they usually present higher values of psychopathological variables.
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Ansiedade , Depressão , Humanos , Masculino , Feminino , Ansiedade/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Transtornos de Ansiedade , Inquéritos e QuestionáriosRESUMO
Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the LTL and mtDNA-CN in relapsing-remitting MS (RRMS). We included 10 healthy controls, 75 patients with RRMS, 50 of whom had an Expanded Disability Status Scale (EDSS) from 0 to 3 (mild to moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). We use the Real-Time Polymerase Chain Reaction (qPCR) technique to quantify absolute LTL and absolute mtDNA-CN. ANOVA test show differences between healthy control vs. severe disability RRMS and mild-moderate RRMS vs. severe disability RRMS (p = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, p = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, p = 0.0018, cut-off < 3.0875 Kb, sensitivity = 75%, specificity = 62%), whereas the prediction is improved with a logistic regression model including LTL plus age (AUC = 0.762, p = 0.0001, sensitivity = 79.17%, specificity = 80%). These results show that LTL is a biomarker of disability in RRMS and is correlated with mtDNA-CN in mild-moderate RRMS patients.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla/genética , DNA Mitocondrial/genética , Variações do Número de Cópias de DNA , Leucócitos , Telômero/genéticaRESUMO
Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, which leads to neurodegeneration and progressive disability. Approximately 30 to 50% of patients do not respond optimally to disease-modifying therapies (DMTs), and therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of the HLA-DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3) was used to classify the therapeutic response. Patients were classified as follows: (a) controls: patients who achieved NEDA-3; (b) cases: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA-DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were GG 50.5%, GA 34.3%, and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p = 0.6). We concluded that in Mexican patients with MS, HLA-DRB1*0403 was not associated with the therapeutic response to DMTs.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética , Cadeias HLA-DRB1/genética , Predisposição Genética para Doença , Estudos de Casos e Controles , GenótipoRESUMO
Approximately 30% of patients with systemic lupus erythematosus (SLE) present steroid resistance (SR). Macrophage migration inhibition factor (MIF) and P-glycoprotein (P-gp) could be related to SR. This work aims to evaluate the relationship between MIF and P-pg serum levels in SR in SLE. Methods: Case−control study including 188 SLE patients who were divided into two groups (90 in the steroid-resistant group and 98 in the steroid-sensitive (SS) group) and 35 healthy controls. MIF and P-gp serum levels were determined by ELISA. Multivariable logistic regression and chi-squared automatic interaction detection (CHAID) were used to explore risk factors for SR. Results: The steroid-resistant group presented higher MIF and P-gp serum levels in comparison with the SS (p < 0.001) and reference (p < 0.001) groups. MIF correlated positively with P-gp (rho = 0.41, p < 0.001). MIF (≥15.75 ng/mL) and P-gp (≥15.22 ng/mL) were a risk factor for SR (OR = 2.29, OR = 5.27). CHAID identified high P-gp as the main risk factor for SR and high MIF as the second risk factor in those patients with low P-gp. Conclusions: An association between MIF and P-gp serum levels was observed in SR. CHAID identified P-gp ≥ 15.22 ng/mL as the main risk factor for SR. More studies are needed to validate these results.
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Lúpus Eritematoso Sistêmico , Fatores Inibidores da Migração de Macrófagos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Estudos de Casos e Controles , Humanos , Oxirredutases Intramoleculares , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Fatores Inibidores da Migração de Macrófagos/metabolismo , EsteroidesRESUMO
Oxidative stress (OS) has been linked to cell damage and chronic disease development; however, the study of psychological factors related with OS has been limited, as has its relationship with biochemical and personal variables. Therefore, the aim of this study was to evaluate the association between a wide variety of personal, psychological, and biochemical factors with OS in a sample of healthy Mexican people. A total of 134 participants, from which 70 (52%) were women, without known chronic conditions were included in the study, and the molecule 8-hydroxy-2'-deoxyguanosine (8-OHdG) was also measured as a marker of OS. We observed in the multivariate analysis of the whole sample that depressive symptoms (measured with CES-D scale) were the only psychological variable significantly associated (positively) with 8-OHdG. In addition, the following sociodemographic variables were associated with 8-OHdG: age, schooling (positively correlated), and the frequency of vitamins/antioxidant consumption (negatively correlated). The biochemical variables of erythrocytes in urine and amylase were positively correlated with 8-OHdG, while glucose was negatively correlated with it. Additional biochemical variables were associated in the multivariate analysis of each sex, including the positive correlation of LDL-cholesterol, LDH enzyme, lymphocytes, and the negative correlation of phosphorus and eosinophils in women's samples, as well as the positive correlation of potassium, uric acid, and leucocytes in urine and the negative correlation of erythrocytes and lipase in the men's samples. In conclusion, depression was the only psychological variable positively correlated with 8-OHdG after adjusting for confounders, and new associations with biochemical variables were found with some differences between sexes.
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Hypertension is one of the main risk factors related to cardiovascular mortality, being the levels of blood pressure (BP) related to a variety of personal, anthropometric, biochemical and psychological variables; however, the study evaluating the association of all these factors in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in a sample of relatively healthy subjects has not been performed. The aim of the study was to determine the main variables associated with SBP and DPB in a sample of relatively healthy subjects. A total of 171 participants were included, in which personal, anthropometric, positive and negative psychological variables and biochemical variables were measured. We observed that men showed higher levels of SBP and DBP than women, with more differences for SBP. Among the biochemical factors and SBP, we found that albumin and monocytes were positively correlated with it, while potassium, phosphorus and eosinophils were negatively correlated with it. Additionally, schooling was a constant variable negatively correlated with SBP in all samples (global, men and women). Among psychological variables, we observed that emotional perception was negatively correlated with SBP in men's and women's samples, while autonomy was positively correlated with SBP in the men's sample; however, their association was less when compared with the personal and biochemical variables included in the multivariate model. With regard to DBP, we observed that the biochemical variables, hemoglobin, sodium, uric acid and glucose, were positively correlated with DBP in the global sample, while chloride and BUN were negatively correlated with it. In addition, many personal and behavioral variables, including BMI, age and smoking consumption frequency, also correlated with DBP in the global sample. In conclusion, BP is affected by different factors, and these affect each sex differently.
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Around 30-60% of patients with rheumatoid arthritis (RA) present treatment failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Chitinase-like proteins (CLPs) (YKL-40, YKL-39, SI-CLP) might play a role, as they are associated with the inflammatory process. This study aimed to evaluate CLP utility as a biomarker in the treatment failure of csDMARDs. A case-control study included 175 RA patients classified into two groups based on therapeutic response according to DAS28-ESR: responders (DAS28 < 3.2); non-responders (DAS28 ≥ 3.2). CLP serum levels were determined by ELISA. Multivariable logistic regression and receiver operating characteristic (ROC) curves were used to evaluate CLPs' utility as biomarkers of treatment failure. Non-responders presented higher levels of YKL-40, YKL-39, and SI-CLP compared with responders (all: p < 0.001). YKL-40 correlated positively with YKL-39 (rho = 0.39, p < 0.001) and SI-CLP (rho = 0.23, p = 0.011) and YKL-39 with SI-CLP (rho = 0.34, p < 0.001). The addition of CLPs to the regression models improves diagnostic accuracy (AUC 0.918) compared to models including only clinical classical variables (AUC 0.806) p < 0.001. Non-responders were positive for all CLPs in 35.86%. Conclusions: CLPs could be considered as a useful biomarker to assess treatment failure, due to their association with clinical variables and improvement to the performance of regression models.
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Background: The relationship between serum glycoprotein syndecan-1 and disease activity in rheumatoid arthritis (RA) is still unknown. This study aimed to evaluate whether serum syndecan-1 concentrations are associated with moderate/severe disease activity. Methods: Study Design: This was a cross-sectional study. Seventy-five adult women with RA were classified into (a) moderate/severe RA based on the disease activity score, using the erythrocyte sedimentation rate (DAS28-ESR ≥ 3.2, n = 50), and (b) RA in remission (DAS28-ESR < 2.6, n = 25). Twenty-five healthy women were taken as the reference group. Syndecan-1 levels were determined using enzyme-linked immunosorbent assay (ELISA). High values of serum syndecan-1 levels (≥24 ng/mL) were used to identify the utility values of this biomarker. Results: The patients with RA had higher levels of syndecan-1 than the controls (p < 0.001). RA patients with active disease had higher syndecan-1 levels than RA patients in remission (57.6 vs. 23.5 ng/mL, respectively; p = 0.002). High syndecan-1 concentrations demonstrated the following utility values for identifying disease activity: sensitivity, 84% (95%CI: 71-93); specificity, 52% (95%CI: 31-72); positive predictive value, 78% (95%CI: 70-84); and negative predictive value, 62% (95%CI: 44-77). Conclusions: High syndecan-1 levels have good sensitivity and positive predictive value for identifying disease activity; however, their specificity is limited. Future prospective studies are needed to assess whether syndecan-1 levels can predict treatment failure in RA.
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Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.
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Subfamília B de Transportador de Cassetes de Ligação de ATP , Citocromo P-450 CYP3A , Imunossupressores , Transplante de Rim , Polimorfismo de Nucleotídeo Único , Tacrolimo , Humanos , Citocromo P-450 CYP3A/genética , Transplante de Rim/efeitos adversos , Tacrolimo/sangue , Tacrolimo/farmacocinética , Tacrolimo/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Feminino , Masculino , Polimorfismo de Nucleotídeo Único/genética , Adulto , México , Imunossupressores/farmacocinética , Imunossupressores/sangue , Imunossupressores/administração & dosagem , Pessoa de Meia-Idade , Genótipo , Rejeição de Enxerto/genéticaRESUMO
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects synovial joints and that frequently involves extra-articular organs. A multiplicity of interleukins (IL) participates in the pathogenesis of RA, including IL-6, IL-1ß, transforming growth factor-beta (TGF-ß), and tumor necrosis factor (TNF)-α; immune cells such as monocytes, T and B lymphocytes, and macrophages; and auto-antibodies, mainly rheumatoid factor and anti-citrullinated protein antibodies (ACPAs). Skeletal muscle is also involved in RA, with many patients developing muscle wasting and sarcopenia. Several mechanisms are involved in the myopenia observed in RA, and one of them includes the effects of some interleukins and myokines on myocytes. Myostatin is a myokine member of the TGF-ß superfamily; the overproduction of myostatin acts as a negative regulator of growth and differentiates the muscle fibers, limiting their number and size. Recent studies have identified abnormalities in the serum myostatin levels of RA patients, and these have been found to be associated with muscle wasting and other manifestations of severe RA. This review analyzes recent information regarding the relationship between myostatin levels and clinical manifestations of RA and the relevance of myostatin as a therapeutic target for future research.
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Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan-Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22-4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16-0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid.
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Cognition is a set of brain processes that allow the individual to interact with their environment. Multiple sclerosis (MS) is a chronic inflammatory disease that affects the cerebral white matter of the brain cortex and spinal cord, leading to cognitive impairment (CI) in 40-60% of the patients. Many studies have determined that CI is linked to genetic risk factors. We aimed to evaluate the association between BDNF gene rs6265 polymorphism and cognitive impairment in Mexican patients with MS by performing a case-control study. Mestizo-Mexican patients diagnosed with MS based on McDonald's criteria were enrolled. Cases were MS patients with CI (n = 31) while controls were MS patients without CI (n = 31). To measure cognitive functioning in MS patients, a neuropsychological screening battery for MS (NSB-MS) was used. Genotyping of the rs6265 gene variant was performed using quantitative real-time PCR (qPCR) with TaqMan probes. The results showed no statistically significant differences in sociodemographic and disease variables between case and control groups. qPCR analysis showed that there were 68% Val/Val wild-type homozygotes, 29% Val/Met polymorphic heterozygotes, and 3% Met/Met polymorphic homozygotes. The presence of BDNF gene rs6265 polymorphism showed an increased probability (3.6 times) of global cognitive impairment.
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Disfunção Cognitiva , Esclerose Múltipla , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , Estudos de Casos e Controles , Esclerose Múltipla/genética , Polimorfismo Genético , Disfunção Cognitiva/genéticaRESUMO
The use of complementary therapies is highly prevalent among patients with rheumatoid arthritis (RA). Nevertheless, the use of complementary medicine could involve problems in the following of scientifically accepted treatments. To date, there is limited information regarding the association of nonconventional therapies with problems regarding compliance with the treatment. Therefore, the objective of this study was to identify whether the utilization of complementary therapies is associated with a high risk of problems regarding therapeutic adherence to conventional synthetic disease-modifying anti-rheumatic drugs (cs-DMARDs) in RA patients. A survey was performed with RA patients in an outpatient rheumatology clinic in a university hospital; the use of complementary therapies, as well as their type, was identified. To assess problems with therapeutic adherence, we used the four-item Morisky-Green scale. A comprehensive assessment of clinical and therapeutic characteristics was performed. Univariable and multivariable models were performed to identify the risk of problems with therapeutic adherence in users of complementary therapies. In total, 250 RA patients were included; 92% used complementary therapies. Of them, the most frequently used were herbal medicine (65%), homeopathy (64%), and cannabis and its derivatives (51%). In the univariable logistic regression analysis, the factors associated with problems in the therapeutic adherence to cs-DMARDs were age (p = 0.019), the presence of other comorbidities (p = 0.047), and the use of complementary therapies (p = 0.042). After controlling for potential confounders, the use of complementary therapies increased the risk of problems with therapeutic adherence to cs-DMARDs (adjusted OR = 2.84, 95% CI = 1.06-7.63, p = 0.037). We concluded that the use of complementary therapies increases the risk of problems with therapeutic adherence. Therefore, for physicians and healthcare professionals, the early identification of the use of nonconventional therapies in their RA patients is required, followed by a directed discussion with their patients about the risks and benefits to which they could be exposed to complementary therapies.
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STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods-A case-control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results-The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions-In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients.
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Doenças Autoimunes , Interferon gama , Lúpus Eritematoso Sistêmico , Fator de Transcrição STAT4 , Pré-Escolar , Humanos , Alelos , Doenças Autoimunes/genética , Doenças Autoimunes/metabolismo , Estudos de Casos e Controles , Citocinas/genética , Predisposição Genética para Doença , Interferon gama/genética , Interleucina-17/genética , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT4/genéticaRESUMO
Somatization and number of diseases are interrelated variables, whose association with stress-coping strategies, according to sex, has not been investigated. Therefore, the aim of this study was to investigate such association in a sample of the Mexican general population. The general population was invited to answer an electronic questionnaire via the social networks-e-mail, WhatsApp and Facebook-by the research team. A sample of 1008 adults was obtained, of which 62.2% were women, in whom we detected higher levels of negative psychological variables, somatization and number of diseases and lower levels of sleep quality. Positive moderate correlations were found between depresion, anxiety and stress with somatization, on one hand, and with the number of diseases, on the other, and negative moderate correlations were found between sleep quality and the two dependent variables. As for the coping strategies, self-blame, behavioral disengagement, denial, self-distraction and substance use were positively correlated with somatization. Of these, self-blame, substance use, and self-distraction also showed a positive correlation with number of diseases in both sexes. Negative correlations were detected for active coping and the two dependent variables in men and for religion and planning with somatization in women. In conclusion, the coping strategies showed significant correlations with somatization and number of diseases in both sexes.
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ABSTRACT: Irisin stimulates osteoblast differentiation increasing bone mass a decreasing in irisin levels might contribute to osteoporotic fractures in inflammatory diseases. To date, there is controverted whether irisin levels are associated with osteoporotic fractures in rheumatoid arthritis (RA). Therefore, we evaluate the association of serum irisin with osteoporotic Vertebral Fractures (VFs) in women with RA.A total of 148 women with RA was included in the study.Clinical characteristics and risk factors of VFs was evaluated. For measurement of bone mineral density we included the assessment of lumbar spine (AP L1-L4) and Femoral Neck by dual-energy X-ray absorptiometry (DXA). VFs were evaluated by lateral vertebral assessment (LVA) of the dorsal and lumbar regions using X-ray and digital vertebral morphometry by DXA, using the Genant scale. Serum irisin levels were measured by ELISA. A reference group of 97 women with non-rheumatic diseases were included to compare irisin levels.RA patients had a median age of 59âyears and 41% had osteoporosis. Seventy three (49%) had VFs. Lower irisin levels were observed in RA patients compared to controls (94â±â74 vs 135â±â103, Pâ<â.001). Irisin concentrations were lower in RAâ+âVFs than RA non-VFs (74â±â42 vs 113â±â92âng/mL, Pâ=â.001). In the multivariable logistic regression analysis the low 50 percentile irisin levelsâ<â73âng/mL (OR:3.1, 95% CI:1.55-6.2, Pâ=â.001), and disease duration of RA (OR:1.04, 95% CI:1.001-1.08, Pâ=â.04) were associated with an increase in the risk of VFs.A decrease of irisin levels is associated to VFs in RA. These results are valuable to consider that RA patients with low levels of irisin are in a potential risk of VFs.
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Artrite Reumatoide/complicações , Fibronectinas/sangue , Vértebras Lombares/diagnóstico por imagem , Fraturas por Osteoporose/sangue , Fraturas da Coluna Vertebral/etiologia , Absorciometria de Fóton , Idoso , Artrite Reumatoide/sangue , Biomarcadores/sangue , Densidade Óssea , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
ABSTRACT: Myostatin is a cytokine produced and released by myocytes that might have an outstanding role not only in muscle wasting during cachexia but also in inflammation. Herein we explore the association between myostatin levels and inflammatory parameters in rheumatoid arthritis (RA).One hundred twenty-seven women without rheumatic diseases and 84 women with a diagnosis of RA were assessed in a cross-sectional study. Outcomes reflecting the activity of the arthritis including Disease Activity Score (DAS28-ESR) and impairment in functioning by the Health Assessment Questionnaire-Disability Index were assessed in RA. We obtained Skeletal muscle mass index (SMI), fat-free mass index (FFMI), and fat mass index using dual-energy x-ray absorptiometry. Serum myostatin was determined by enzyme-linked immunosorbent assay. Myostatin levels were correlated with disease activity and parameters of muscle mass.The SMI was lower and concentration of myostatin was higher in RA patients than in controls (Pâ=â.008 and Pâ<â.001, respectively). Myostatin significantly positively correlated with C-reactive protein (rhoâ=â0.48, Pâ<â.001), erythrocyte sedimentation rate (rhoâ =â0.28, Pâ=â.009), and DAS28-ESR (rhoâ=â0.22, Pâ =â.04), and negatively correlated with SMI (rhoâ=â-0.29, Pâ=â.008), (FFMI) (rhoâ=â-0.24, Pâ=â.027). In the multivariate logistic regression analysis, levels of myostatin remained associated with disease activity in RA (Pâ=â.027).In our study, myostatin was associated with disease activity in RA patients, suggesting a mechanistic link between myostatin, muscle wasting and inflammation in RA.
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Artrite Reumatoide/sangue , Inflamação/sangue , Miostatina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
An important goal in the management of systemic lupus erythematosus (SLE) is the prediction of relapses. This study assesses whether anti-nucleosome antibodies (anti-NCS) increase the risk of renal relapse in inactive SLE. A prospective cohort of 115 patients with inactive SLE (M-SLEDAI ≤ 2) were followed for 12 months to assess the development of relapse (increase of M-SLEDAI ≥ 4) and specific renal flare (renal SLEDAI ≥ 4). At baseline, we identified potential risk factors for relapse, including anti-NCS. At baseline, 18 (16%) of the 115 patients with inactive SLE were anti-NCS positive. At the 12-month follow-up, anti-NCS-positive patients had a higher incidence of renal relapse compared to anti-NCS-negative patients (38.9% vs 13.4%, respectively). In Cox regression analysis, after adjusting for age, disease duration, anti-dsDNA, and immunosuppressive drugs, the presence of anti-NCS positivity at baseline increased the risk of renal relapse (HR: 5.31, 95% CI 2.03-13.92). Nevertheless, there were no differences in the incidence of other relapses in anti-NCS-positive versus anti-NCS-negative. Our results indicate that in inactive SLE, anti-NCS determination can be useful for identifying patients with a higher risk of developing renal relapse. Interestingly, this study identified that continued use of oral immunosuppressive therapy in patients with inactive SLE can reduce the risk of renal relapse.
Assuntos
Anticorpos Antinucleares/metabolismo , DNA/imunologia , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Prednisona/administração & dosagem , Administração Oral , Adulto , Doenças Assintomáticas , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Prospectivos , Recidiva , Análise de Regressão , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: To date, the association of serum macrophage migration inhibitory factor (MIF) and serum adipokines with lupus nephritis is controversial. OBJECTIVE: To assess the utility of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritis. METHODS: Cross-sectional study including 196 systemic lupus erythematosus (SLE) patients and 52 healthy controls (HCs). Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal SLE involvement was investigated by renal-SLEDAI. MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed the correlations of quantitative variables by Spearman correlation (rs). Multivariable linear regression adjusted the variables associated with the severity of proteinuria. RESULTS: SLE patients had higher MIF (p = 0.02) and adiponectin (p < 0.001) than HCs. Patients with renal SLE involvement (n = 43) had higher adiponectin (19.0 vs 13.3 µg/mL, p = 0.002) and resistin (10.7 vs 8.9 ng/mL, p = 0.01) than patients with non-renal SLE (n = 153). Proteinuria correlated with high adiponectin (r s = 0.19, p < 0.009) and resistin (r s = 0.26, p < 0.001). MIF (r s = 0.27, p = 0.04). Resistin correlated with increased creatinine (r s = 0.18, p = 0.02). High renal-SLEDAI correlated with adiponectin (r s = 0.21, p = 0.004). Multiple linear regression showed that elevated adiponectin (p = 0.02), younger age (p = 0.04) and low MIF (p = 0.02) were associated with the severity of proteinuria. Low MIF and high adiponectin levels interacted to explain the association with the severity of proteinuria (R2 = 0.41). CONCLUSIONS: High adiponectin combined with low MIF concentrations int+eract to explain the severity of proteinuria in renal SLE. These findings highlight the relevance of adiponectin, resistin and MIF as markers of LN.