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A poorly studied issue in women with breast cancer is the role of incretins (GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1)) in the quantity and quality of muscle mass in lean and obese individuals. The current report aims to analyze the patterns of association and the role of incretin in muscle functionality and body composition in women with cancer compared with healthy women (mammography BI-RADS I or II) to elucidate whether GIP and GLP-1 can be used to estimate the risk, in conjunction with overweight or obesity, for breast cancer. We designed a case-control study in women with a breast cancer diagnosis confirmed by biopsy in different clinical stages (CS; n = 87) and healthy women with a mastography BI-RADS I or II within the last year (n = 69). The women were grouped according to body mass index (BMI): lean (<25 kg/m2BS), overweight (≥25-<30 kg/m2BS), and obese (≥30 kg/m2BS). We found that GLP-1 and GIP levels over 18 pg/mL were associated with a risk of breast cancer (GIP OR = 36.5 and GLP-1 OR = 4.16, for the entire sample), particularly in obese women (GIP OR = 8.8 and GLP-1 OR = 6.5), and coincidentally with low muscle quality indexes, showed an association between obesity, cancer, incretin defects, and loss of muscle functionality.
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Insulin levels, adipocytokines, and inflammatory mediators trigger benign breast disease (BBD) and breast cancer (BC). The relationship between serum adipocytokines levels, overweight-obesity, metabolic disturbs, and BC is unclear. Methods: To analyze the serum levels of the adipocytokines, insulin, and the HOMA IR in women without breast disease, with BBD or BC, and the role of these as risk factors for benign breast disease or breast cancer. Results: Adipsin values > 0.91 and visfatin levels > 1.18 ng/mL represent a risk factor to develop BBD in NBD lean women (OR = 18; and OR = 12). Data in overweight-obese women groups confirm the observation due to insulin levels > 2.6 mU/mL and HOMA IR > 0.78, with OR = 60.2 and 18, respectively; adipsin OR = 26.4, visfatin OR = 12. Breast cancer risk showed a similar behavior: Adipsin risk, adjusted by insulin and visfatin OR = 56 or HOMA IR and visfatin OR = 22.7. Conclusion: Adipose tissue is crucial for premalignant and malignant tissue transformation in women with overweight-obesity. The adipocyte−breast epithelium interaction could trigger a malignant transformation in a continuum, starting with BBD as premalignant disease, especially in overweight-obese women.
Assuntos
Doenças Mamárias , Neoplasias da Mama , Resistência à Insulina , Adipocinas , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Fator D do Complemento , Feminino , Humanos , Insulina , Nicotinamida Fosforribosiltransferase , Obesidade , Sobrepeso/epidemiologia , Prevalência , Fatores de RiscoRESUMO
ABSTRACT: Increased neutrophil extracellular trap (NET) formation associates with high cardiovascular risk and mortality in patients with end-stage renal disease (ESRD). However, the effect of transplantation on NETs and its associated markers remains unclear. This study aimed to characterize circulating citrullinated Histone H3 (H3cit) and Peptidyl Arginase Deiminase 4 (PAD4) in ESRD patients undergoing transplantation and evaluate the ability of their neutrophils to release NETs.This prospective cohort study included 80 healthy donors and 105 ESRD patients, out of which 95 received a transplant. H3cit and PAD4 circulating concentration was determined by enzyme-linked immunosorbent assay in healthy donors and ESRD patients at the time of enrollment. An additional measurement was carried out within the first 6 months after transplant surgery. In vitro NET formation assays were performed in neutrophils isolated from healthy donors, ESRD patients, and transplant recipients.H3cit and PAD4 levels were significantly higher in ESRD patients (H3cit, 14.38âng/mL [5.78-27.13]; PAD4, 3.22âng/mL [1.21-6.82]) than healthy donors (H3cit, 6.45âng/mL [3.30-11.65], Pâ<â.0001; PAD4, 2.0âng/mL [0.90-3.18], Pâ=â.0076). H3cit, but not PAD4, increased after transplantation, with 44.2% of post-transplant patients exhibiting high levels (≥ 27.1âng/mL). In contrast, NET release triggered by phorbol 12-myristate 13-acetate was higher in neutrophils from ESRD patients (70.0% [52.7-94.6]) than healthy donors (32.2% [24.9-54.9], Pâ<â.001) and transplant recipients (19.5% [3.5-65.7], Pâ<â.05).The restoration of renal function due to transplantation could not reduce circulating levels of H3cit and PAD4 in ESRD patients. Furthermore, circulating H3cit levels were significantly increased after transplantation. Neutrophils from transplant recipients exhibit a reduced ability to form NETs.
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Armadilhas Extracelulares , Falência Renal Crônica/terapia , Transplante de Rim/métodos , Neutrófilos/patologia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: The immunologic, metabolic and anthropometric disturbances of overweight-obesity phenomena are risk factors to breast cancer (BC), particularly in proliferative benign breast disease women (PBBD). OBJECTIVE: To describe the adipocytokine levels, metabolic alteration and anthropometric characteristics in PBBD and its role as risk estimator to BC in a population with high overweight-obesity prevalence. MATERIAL AND METHODS: A cross-sectional study. We realized nutritional diagnosis, anthropometry, and we calculated the waist-height rate (WHR); serum measurement of adipocytokines, insulin and glucose and, HOMA IR determination in 27 PBBD and 27 BC women. We calculated mean, standard deviation, Pearson and Spearman correlation coefficients, Odds Ratio (OR) and confidence intervals through logistic regression as risk estimators of BC; p < 0.05 values were considered significant. RESULTS: Mean age in the PBBD group was minor than BC group, the humeral diameter was greater in BC group women. We did not find differences in anthropometry or adipocytokine levels; in both groups, the predominant somatotype was the endo-mesomorphic. We found higher insulin levels in BC group and a higher percentage of women with WHR > 0.5 too. The WHR > 0.5 + age over 50 were considered risk estimators to develop breast cancer in PBBD women group. CONCLUSION: The WHR >0.5 in women with PBBD over 50 years old could be considered an anthropometric risk estimator to develop BC.
INTRODUCCIÓN: La inflamación, las alteraciones metabólicas y antropométricas del fenómeno sobrepeso-obesidad son factores de riesgo para cáncer de mama (CaM) particularmente en mujeres con enfermedad mamaria benigna proliferativa (EMBP). OBJETIVO: Describir los niveles de adipocitocinas, alteraciones metabólicas y antropométricas en la EMBP y su papel como estimadores de riesgo para CaM en una población con prevalencia de sobrepeso-obesidad de más del 70%. MATERIAL Y MÉTODOS: Estudio transversal analítico en 27 mujeres con CaM y 27 con EMBP. Se realizó diagnóstico nutricional, antropometría y cálculo del índice cintura-talla (ICT); determinación sérica de adipocitocinas, insulina, glucosa y estimación de HOMA IR. Se calcularon promedio y desviaciones estándar, correlaciones de Pearson y Spearman; Odds Ratio (OR) e intervalos de confianza mediante regresión logística como estimadores de riesgo de CaM. Se consideró significativo un valor de p < 0.05. RESULTADOS: La edad del grupo EMBP fue menor. No se observaron diferencias en adipocitocinas ni antropometría (excepto el diámetro humeral fue mayor en CaM). Se observaron mayores niveles de insulina en CaM, y mayor porcentaje de mujeres con ICT > 0.5. El ICT > 0.5 + edad > 50 fueron estimadores de riesgo para CaM. CONCLUSIÓN: Un ICT > 0.5 en mujeres mayores de 50 años podría ser un estimador antropométrico de riesgo de CaM en mujeres con EMBP.
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HLA-DRB1 alleles has been found implicated in susceptibility to autoimmune hepatitis (AIH) in populations from different genetic backgrounds. In Mexicans, HLA-DRB1*04:04 is recognized as a risk allele for AIH but, to date, there is no high-resolution data supporting this association. Also, the association of other nonclassical HLA genes, such as TNF-LTA locus, have not, to our knowledge, been evaluated in this population. The association of HLA-DRB1 alleles determined by sequence-based typing and two polymorphisms in the TNF locus with AIH in a sample of Mexican patients was evaluated. Fifty-six patients from Guadalajara, Mexico, diagnosed with AIH and 115 age-gender matched healthy volunteer blood donors, were genotyped for HLA-DRB1 by the sequencing exon 2 and for TNFA-308G>A and LTA + 252A>G polymorphisms. Increased frequencies of both HLA-DRB1*04:04:01 and *16:02:01:01 alleles (OR = 2.91; 95% CI = 1.08-7.84) and the haplotype (DRB1-TNFA-LTA) *04:04:01-G-A (OR = 5.33; 95% CI = 1.32-21.49) were observed in AIH patients. However, after corrections for multiple comparisons, associations were not significant. In conclusion, our study does not support the association of HLA-DRB1*04:04:01 with the susceptibility to AIH in Mexican population. More studies including patients from other Mexican regions and considering other genetic, immunological, and environmental factors should be performed.
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Cadeias HLA-DRB1/genética , Hepatite Autoimune/genética , Fator de Necrose Tumoral alfa/genética , Feminino , Humanos , Masculino , México , Razão de ChancesRESUMO
BACKGROUND: The Interleukin (IL)-1 family of cytokines plays a key role in the inflammatory response. Genes coding for IL-1α, IL-1ß, and IL-1Ra are located together as a block gene known as the IL-1 cluster. This genomic region shows wide nucleotide variability, and some polymorphisms have been widely studied and associated with features related to the metabolic syndrome. METHODS: Eight polymorphisms within three genes of the IL-1 cluster, including IL1A (rs3783553, rs17561, and rs1800587), IL1B (rs1143634, rs1143627, and rs16944) and IL1RN (rs419598 and rs2234663) were genotyped in 460 Mexican adolescents. Genotype and haplotype frequencies are reported, as well as the linkage disequilibrium analysis. Genetic associations with some anthropometric and metabolic traits were evaluated. RESULTS: Allele frequencies were similar to those found in other populations, and genotype proportions were according to the Hardy-Weinberg equilibrium. Seven haplotypes were observed at frequencies ≥5%. Of the entire cluster, only the rs17561-rs1800587 and rs1143627-rs16944 pairs showed highest and significant linkage disequilibrium values. An haplotype of IL1A, rs17561T-rs1800587T, was significantly associated with increase in body mass index in males (p <0.008), whereas IL1B and IL1RN variants showed associations with insulin, and hs-CRP (p <0.05). CONCLUSIONS: Some MetS parameters seem to be influenced by variations in the IL-1 gene cluster in Mexican adolescents. These variations may confer risk for metabolic alterations from early ages, and and these risks may be different when variables such as sex are considered. Strategies leading to generate protective behaviors could be designed to take into account specific variations in the IL-1 gene cluster and biological conditions such as sex.
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Índice de Massa Corporal , Frequência do Gene/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1alfa/genética , Interleucina-1beta/genética , Adolescente , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , México , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
OBJECTIVE: Fibrin glues have not been consistently successful in preventing the dehiscence of high-risk colonic anastomoses. Fibrinogen and thrombin concentrations in glues determine their ability to function as sealants, healers, and/or adhesives. The objective of the current study was to compare the effects of different concentrations of fibrinogen and thrombin on bursting pressure, leaks, dehiscence, and morphology of high-risk ischemic colonic anastomoses using fibrin glue in rats. METHODS: Colonic anastomoses in adult female Sprague-Dawley rats (weight, 250-350 g) treated with fibrin glue containing different concentrations of fibrinogen and thrombin were evaluated at post-operative day 5. The interventions were low-risk (normal) or high-risk (ischemic) end-to-end colonic anastomoses using polypropylene sutures and topical application of fibrinogen at high (120 mg/mL) or low (40 mg/mL) concentrations and thrombin at high (1000 IU/mL) or low (500 IU/mL) concentrations. RESULTS: Ischemia alone, anastomosis alone, or both together reduced the bursting pressure. Glues containing a low fibrinogen concentration improved this parameter in all cases. High thrombin in combination with low fibrinogen also improved adherence exclusively in low-risk anastomoses. No differences were detected with respect to macroscopic parameters, histopathology, or hydroxyproline content at 5 days post-anastomosis. CONCLUSIONS: Fibrin glue with a low fibrinogen content normalizes the bursting pressure of high-risk ischemic left-colon anastomoses in rats at day 5 after surgery.
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Colo/cirurgia , Adesivo Tecidual de Fibrina/uso terapêutico , Fibrinogênio/administração & dosagem , Isquemia/prevenção & controle , Trombina/administração & dosagem , Adesivos Teciduais/uso terapêutico , Anastomose Cirúrgica , Animais , Colágeno/análise , Colo/irrigação sanguínea , Colo/patologia , Feminino , Hidroxiprolina/análise , Isquemia/etiologia , Pressão , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , CicatrizaçãoRESUMO
OBJECTIVE: Fibrin glues have not been consistently successful in preventing the dehiscence of high-risk colonic anastomoses. Fibrinogen and thrombin concentrations in glues determine their ability to function as sealants, healers, and/or adhesives. The objective of the current study was to compare the effects of different concentrations of fibrinogen and thrombin on bursting pressure, leaks, dehiscence, and morphology of high-risk ischemic colonic anastomoses using fibrin glue in rats. METHODS: Colonic anastomoses in adult female Sprague-Dawley rats (weight, 250-350 g) treated with fibrin glue containing different concentrations of fibrinogen and thrombin were evaluated at post-operative day 5. The interventions were low-risk (normal) or high-risk (ischemic) end-to-end colonic anastomoses using polypropylene sutures and topical application of fibrinogen at high (120 mg/mL) or low (40 mg/mL) concentrations and thrombin at high (1000 IU/mL) or low (500 IU/mL) concentrations. RESULTS: Ischemia alone, anastomosis alone, or both together reduced the bursting pressure. Glues containing a low fibrinogen concentration improved this parameter in all cases. High thrombin in combination with low fibrinogen also improved adherence exclusively in low-risk anastomoses. No differences were detected with respect to macroscopic parameters, histopathology, or hydroxyproline content at 5 days post-anastomosis. CONCLUSIONS: Fibrin glue with a low fibrinogen content normalizes the bursting pressure of high-risk ischemic left-colon anastomoses in rats at day 5 after surgery. .
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Animais , Feminino , Colo/cirurgia , Adesivo Tecidual de Fibrina/uso terapêutico , Fibrinogênio/administração & dosagem , Isquemia/prevenção & controle , Trombina/administração & dosagem , Adesivos Teciduais/uso terapêutico , Anastomose Cirúrgica , Colágeno/análise , Colo/irrigação sanguínea , Colo/patologia , Hidroxiprolina/análise , Isquemia/etiologia , Pressão , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , CicatrizaçãoRESUMO
AIM: To assess whether the use of fibrin sealant shortens the closure time of postoperative enterocutaneous fistulas (ECFs). METHODS: The prospective case-control study included 70 patients with postoperative ECFs with an output of < 500 mL/d, a fistulous tract of > 2 cm and without any local complication. They were divided into study (n = 23) and control groups (n = 47). Esophageal, gastric and colocutaneous fistulas were monitored under endoscopic visualization, which also allowed fibrin glue application directly through the external hole. Outcome variables included closure time, time to resume oral feeding and morbidity related to nutritional support. RESULTS: There were no differences in mean age, fistula output, and follow-up. Closure-time for all patients of the study group was 12.5 +/- 14.2 d and 32.5 +/- 17.9 d for the control group (P < 0.001), and morbidity related to nutritional support was 8.6% and 42.5%, respectively (P < 0.01). In patients with colonic fistulas, complete closure occurred 23.5 +/- 19.5 d after the first application of fibrin glue, and spontaneous closure was observed after 36.2 +/- 22.8 d in the control group (P = 0.36). Recurrences were observed in 2 patients because of residual disease. One patient of each group died during follow-up as a consequence of septic complications related to parenteral nutrition. CONCLUSION: Closure time was significantly reduced with the use of fibrin sealant, and oral feeding was resumed faster. We suggest the use of fibrin sealant for the management of stable enterocutaneous fistulas.
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Adesivo Tecidual de Fibrina/uso terapêutico , Fístula Intestinal/cirurgia , Complicações Pós-Operatórias/cirurgia , Adesivos Teciduais/uso terapêutico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Fístula Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Although commonly used in adults to detect early atherosclerosis, the value of the carotid intima-media thickness (CIMT) in children and adolescents is not clear. This marker has an inheritable component that supports the notion of a genetic influence. Among the genes studied as candidates for atherosclerosis development are those for chemokines, cytokines, and adhesion molecules because of their participation in atheroma formation through monocyte recruitment and migration. METHODS: We analyzed the relationship between CIMT and functional polymorphic variants in the genes for chemokines and proinflammatory cytokines associated with cardiovascular events in adults in lean and obese but otherwise healthy 6- to 19-year-old subjects. RESULTS: In the obese group, systolic blood pressure correlated negatively (r =-0.332; p = 0.008) and the TNF-308A allele correlated positively (r = 0.262; p = 0.040) with CIMT. The mean CIMT was higher in obese individuals with the TNF-308A allele than in those with TNF-308G allele (p = 0.041). In a multiple regression model for the total population, an increase in CIMT was explained by body mass index, systolic and diastolic blood pressure, and the TNF-308A and CCL2-2518A alleles (r(2) = 0.321; p = 0.022). CONCLUSIONS: This study contributes to the understanding of the pathophysiology of atherosclerosis and suggests that genetic markers of an increased inflammatory response and its deleterious effects are already present in obese children and adolescents.