RESUMEN

BACKGROUND: Stress is a potentially significant risk factor for the occurrence and progression of inflammatory bowel disease (IBD). METHODS: The study analyzed the level of stress, anxiety, and depression in patients with Crohn's disease (CD; n = 50) and ulcerative colitis (UC; n = 54) in comparison with non-IBD controls (n = 100), using Perceived Stress Scale (PSS), Patient Health Questionnaire (PHQ-9), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Additionally, a correlation between psychological scores and expression of IL17A, IL17F, and IL23A genes in the intestinal mucosa of IBD patients was assessed. RESULTS: Compared to controls, CD and UC patients had higher PSS (P = 4 × 10-14, P = 2.5 × 10-16), PHQ-9 (P = 2 × 10-16, P = 2 × 10-16), HADS depression (P = 2.6 × 10-10, P = 2.5 × 10-11), and HADS anxiety (P = 3.5 × 10-9, P = 1.2 × 10-11). We found a positive correlation between PSS and IL17F mRNA (rs = 0.43, P = .036) while HADS depression and HADS anxiety positively correlated with the IL23A mRNA in inflamed ileal mucosa of CD subjects (rs = 0.55, P = .0048; rs = 0.53, P = .0062). CONCLUSIONS: A significantly higher psychological distress was identified in IBD patients. CD patients with increased ileal expression of IL17F and IL23A genes had higher PSS and HADS, suggesting a potential interplay between psychological distress and inflammation.

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The study found elevated levels of perceived stress, depression, and anxiety in IBD. IL17F mRNA correlated with perceived stress while IL23A mRNA correlated with anxiety and depression (HADS) in the ileal mucosa of CD patients.

RESUMEN

Novel allergen immunotherapy (AIT) approaches necessitate the use of more effective and safe therapeutics, which can be accomplished by employing novel adjuvants for improved innate immune cell activation, as well as hypoallergenic allergen forms. In this study, we investigate the immunomodulatory effects of a chimera rBet v 1a-BanLecwt (rBv1a-BLwt; Cwt) composed of the major birch pollen allergen Bet v 1a and banana lectin (BanLecwt; BLwt) and two novel chimeras, rBv1l-BLH84T (rBet v 1l-BanLecH84T; C1) and rBLH84T-Bv1l (rBanLecH84T-Bet v 1l; C2), both composed of BLH84T and hypoallergenic birch pollen allergen Bv1l in the co-culture model Caco-2/THP-1, and PBMCs from donors with birch pollen allergy. The chimeric molecules rBv1l-BLH84T (C1) and rBLH84T-Bv1l (C2) were created in silico and then produced in E. coli using recombinant DNA technology. Real-time PCR analysis of gene expression following compound treatment in the co-culture model revealed that all three chimeras have the potential to induce the anti-inflammatory cytokine IL-10 gene expression in Caco-2 cells and IFN-γ gene expression in THP-1 cells. Sandwich ELISA revealed that Cwt increased IL-10 secretion and IFN-/IL-4 levels in PBMCs from birch pollen allergic donors, whereas C1 and C2 were less effective. The findings suggest that Cwt should be analyzed further due to its potential benefit in AIT.

Asunto(s)

Betula , Hipersensibilidad , Humanos , Betula/genética , Células CACO-2 , Interleucina-4/genética , Polen , Interleucina-10/genética , Técnicas de Cocultivo , Regulación hacia Arriba , Escherichia coli/genética , Proteínas de Plantas/genética , Antígenos de Plantas/genética , Alérgenos/genética , Expresión Génica , Proteínas Recombinantes

RESUMEN

Inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are complex diseases whose etiology is associated with genetic and environmental risk factors, among which are diet and gut microbiota. To date, IBD is an incurable disease and the main goal of its treatment is to reduce symptoms, prevent complications, and improve nutritional status and the quality of life. Patients with IBD usually suffer from nutritional deficiency with imbalances of specific micronutrient levels that contribute to the further deterioration of the disease. Therefore, along with medications usually used for IBD treatment, therapeutic strategies also include the supplementation of micronutrients such as vitamin D, folic acid, iron, and zinc. Micronutrient supplementation tailored according to individual needs could help patients to maintain overall health, avoid the triggering of symptoms, and support remission. The identification of individuals' genotypes associated with the absorption, transport and metabolism of micronutrients can modify future clinical practice in IBD and enable individualized treatment. This review discusses the personalized approach with respect to genetics related to micronutrients commonly used in inflammatory bowel disease treatment.

RESUMEN

Allergen-specific immunotherapy (AIT) is a desensitizing treatment for allergic diseases that corrects the underlined pathological immune response to innocuous protein antigens, called allergens. Recombinant allergens employed in the AIT allowed the production of well-defined formulations that possessed consistent quality but were often less efficient than natural allergen extracts. Combining recombinant allergens with an adjuvant or immunomodulatory agent could improve AIT efficacy. This study aimed to perform structural and functional characterization of newly designed recombinant chimera composed of the Bet v 1, the major birch pollen allergen, and Banana Lectin (BanLec), TLR2, and CD14 binding protein, for the application in AIT. rBet v 1-BanLec chimera was designed in silico and expressed as a soluble fraction in Escherichia coli. Purified rBet v 1-BanLec (33.4 kDa) retained BanLec-associated biological activity of carbohydrate-binding and preserved IgE reactive epitopes of Bet v 1. The chimera revealed secondary structures with predominant ß sheets. The immunomodulatory capacity of rBet v 1-BanLec tested on macrophages showed changes in myeloperoxidase activity, reduced NO production, and significant alterations in the production of cytokines when compared to both rBanLec and rBet v 1. Comparing to rBet v 1, rBet v 1-BanLec was demonstrated to be more efficient promoter of IL-10 production as well as weaker inducer of NO production and secretion of pro-inflammatory cytokines TNFα, and IL-6. The ability of rBet v 1-BanLec to promote IL-10 in together with the preserved 3D structure of Bet v 1 part implies that the construct might exert a beneficial effect in the allergen-specific immunotherapy.

Asunto(s)

Antígenos de Plantas/inmunología , Desensibilización Inmunológica/métodos , Interleucina-10/metabolismo , Macrófagos Peritoneales/inmunología , Musa/inmunología , Lectinas de Plantas/inmunología , Animales , Epítopos de Linfocito B/inmunología , Inmunoglobulina E/inmunología , Interleucina-10/inmunología , Ratones , Proteínas Recombinantes/inmunología

RESUMEN

Fluorescently labeled lectins are useful tools for in vivo and in vitro studies of the structure and function of tissues and various pathogens such as viruses, bacteria, and fungi. For the evaluation of high-mannose glycans present on various glycoproteins, a three-dimensional (3D) model of the chimera was designed from the crystal structures of recombinant banana lectin (BanLec, Protein Data Bank entry (PDB): 5EXG) and an enhanced green fluorescent protein (eGFP, PDB 4EUL) by applying molecular modeling and molecular mechanics and expressed in Escherichia coli. BanLec-eGFP, produced as a soluble cytosolic protein of about 42 kDa, revealed ß-sheets (41%) as the predominant secondary structures, with the emission peak maximum detected at 509 nm (excitation wavelength 488 nm). More than 65% of the primary structure was confirmed by mass spectrometry. Competitive BanLec-eGFP binding to high mannose glycans of the influenza vaccine (Vaxigrip®) was shown in a fluorescence-linked lectin sorbent assay (FLLSA) with monosaccharides (mannose and glucose) and wild type BanLec and H84T BanLec mutant. BanLec-eGFP exhibited binding to mannose residues on different strains of Salmonella in flow cytometry, with especially pronounced binding to a Salmonella Typhi clinical isolate. BanLec-eGFP can be a useful tool for screening high-mannose glycosylation sites on different microorganisms.

Asunto(s)

Escherichia coli , Proteínas Fluorescentes Verdes , Lectinas , Manosa , Polisacáridos , Cristalografía por Rayos X , Escherichia coli/metabolismo , Citometría de Flujo , Proteínas Fluorescentes Verdes/química , Proteínas Fluorescentes Verdes/metabolismo , Lectinas/química , Manosa/química , Musa/metabolismo , Péptidos/química , Lectinas de Plantas/química , Polisacáridos/química , Unión Proteica , Conformación Proteica , Estructura Secundaria de Proteína

RESUMEN

A racemic spirohydantoin derivative with two aromatic substituents, a tetralin and a 4-methoxybenzyl unit, was synthesized and its crystal structure was determined. To define the relationship between molecular stereochemistry and spatial association modes, development of the crystal packing was analyzed through cooperativity of intermolecular interactions. Homo and heterochiral dimeric motifs were stabilized by intermolecular N-H⋅⋅⋅O, C-H⋅⋅⋅O, C-H⋅⋅⋅π interactions and parallel interactions at large offsets (PILO), thus forming alternating double layers. The greatest contribution to the total stabilization came from a motif of opposite enantiomers linked by N-H⋅⋅⋅O bonds (interaction energy=-13.72 kcal/mol), followed by a homochiral motif where the 4-methoxybenzyl units allowed C-H⋅⋅⋅π, C-H⋅⋅⋅O interactions and PILO (interaction energy=-11.56 kcal/mol). The number of the contact fragments in the environment of the tetralin unit was larger, but the 4-methoxybenzyl unit had greater contribution to the total stabilization. The statistical analysis of the data from the Cambridge Structural Database (CSD) showed that this is a general trend. The compound is a potential inhibitor of kinase enzymes and antigen protein-coupled receptors. A correlation between the docking study and the results of the CSD analysis can be drawn. Due to a greater flexibility, the 4-methoxybenzyl unit is more adaptable for interactions with the biological targets than the tetralin unit.

Asunto(s)

Hidantoínas/química , Compuestos de Espiro/química , Tetrahidronaftalenos/química , Cristalografía por Rayos X , Humanos , Hidantoínas/metabolismo , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Simulación del Acoplamiento Molecular , Receptores de Dopamina D3/metabolismo , Compuestos de Espiro/metabolismo , Estereoisomerismo , Tetrahidronaftalenos/metabolismo

RESUMEN

BACKGROUND: Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. METHODS: From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Bax, Fas and FasL) genes' expression levels by real-time PCR, while NFκB transcriptional potency was assessed by electromobility gel shift assay. RESULTS: Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Bax was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NFκB has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. CONCLUSIONS: We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.

Asunto(s)

Apoptosis/genética , Enfermedad de Crohn/patología , Inflamación/genética , Transcriptoma , Adulto , Citocinas/genética , Femenino , Humanos , Inflamación/patología , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Fenotipo , Proyectos Piloto , Adulto Joven

RESUMEN

METHODS: A cross-sectional study was conducted in consecutive newly diagnosed patients with inflammatory bowel disease in a tertiary care referral center. The initial evaluation included patient-reported outcome for stool frequency subscore and rectal bleeding. Endoscopic activity was determined using the Mayo scoring system for ulcerative colitis and the Simple Endoscopic Score for Crohn's disease. Histopathological activity was assessed using a validated numeric scoring system. RESULTS: We included 159 patients (63 Crohn's disease with colonic involvement and 96 with ulcerative colitis). We found significant correlation between the Mayo endoscopic subscoring system and histology activity in ulcerative colitis, while no correlation was found in patients with Crohn's disease. Patient-reported outcome showed inverse correlation with endoscopic and histological activity in Crohn's disease (r s = -0.67; r s = -0.72), while positive correlation was found in ulcerative colitis (r s = 0.84; r s = 0.75). Interpretation and Conclusions. Patient-reported outcome is a practical and noninvasive tool for assessment of disease activity in ulcerative colitis patients but not in Crohn's disease.

RESUMEN

Background: This study analyzed poorly understood relationship of two overlapping conditions: metabolic syndrome (MeS) and inflammatory bowel disease (IBD), both associated with inflammation in the visceral adipose tissue. Methods: Newly diagnosed 104 IBD patients, of which 50 Crohn's disease (CD) and 54 ulcerative colitis (UC), and 45 non-IBD controls were examined for MeS-related obesity and lipid markers. Th-17 immune genes IL17A, IL17F, IL23A, and TLR9 mRNAs were measured in intestinal mucosa by qRT-PCR. Subjects were genotyped for obesity-associated FTO variant rs9939609 by polymerase chain reaction-amplification refractory mutation system. Results: CD was associated with MeS (P = 0.01), while both CD and UC were associated with central obesity (P = 10-5, P = 0.002, respectively) and low levels of high-density lipoprotein (HDL) cholesterol (P = 5 × 10-6, P = 6 × 10-6, respectively). IBD lipid profile was characterized by decreased total and HDL cholesterol, while low-density lipoprotein cholesterol was reduced only in CD. Negative correlations were found between total cholesterol and CD activity index (P = 0.005), waist circumference and IL17A as well as IL17F mRNA levels in inflamed CD colon (P = 0.003, P = 0.001, respectively). Carriers of FTO rs9939609 AA genotype showed increased risk of CD (OR 2.6, P = 0.01). Conclusions: MeS, central obesity, and dyslipidemia could be important for IBD pathogenesis. This could influence therapeutic approaches and prevention strategies in high-risk groups.

Asunto(s)

Inflamación/genética , Enfermedades Inflamatorias del Intestino/genética , Síndrome Metabólico/genética , Obesidad/genética , Grasa Abdominal/metabolismo , Adolescente , Adulto , Anciano , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Colitis Ulcerosa/genética , Colitis Ulcerosa/metabolismo , Enfermedad de Crohn/genética , Enfermedad de Crohn/metabolismo , Estudios Transversales , Citocinas/biosíntesis , Citocinas/genética , Femenino , Regulación de la Expresión Génica/genética , Marcadores Genéticos/genética , Genotipo , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Masculino , Síndrome Metabólico/etiología , Persona de Mediana Edad , Células Th17/inmunología , Adulto Joven

RESUMEN

Background and Objectives: The aim of the study was to determine the association between presences of fatty pancreas (FP) with the features of metabolic syndrome (MeS) in patients with non-alcoholic fatty liver disease (NAFLD) and to establish a new noninvasive scoring system for the prediction of FP in patients with NAFLD. Material and Methods: 143 patients with NAFLD were classified according to FP severity grade into the two groups and evaluated for diagnostic criteria of MeS. All patients underwent sonographic examination with adiposity measurements and the liver biopsy. Liver fibrosis was evaluated semi-quantitatively according to the METAVIR scoring system and using non-invasive markers of hepatic fibrosis. Results: Waist circumference (WC) was predictive for increased risk of FP in NAFLD patients. Elevated fasting plasma glucose, total cholesterol, serum amylase and lipase levels were associated with presence of severe FP (p value = 0.052, p value = 0.007, p value = 0.014; p value = 0.024, respectively). Presence of increased amounts of mesenteric fat was associated with severe FP (p value = 0.013). The results of this study demonstrated highly significant association between NAFLD and presence of FP. The model for predicting the presence of FP was designed with probability value above 6.5. Conclusion: Pancreatic fat accumulation leads to worsening of pancreatic function which in turns exacerbates severity of metabolic syndrome associated with both, NAFLD and NAFPD.

Asunto(s)

Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Páncreas/anomalías , Ultrasonografía/métodos , Adulto , Anciano , Biomarcadores/análisis , Biomarcadores/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/diagnóstico por imagen , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Páncreas/diagnóstico por imagen , Factores de Riesgo , Serbia

RESUMEN

Aim To investigate the immunomodulatory potential of a chimera composed of the receptor-binding domain of hemagglutinin 1 (H1s) from Influenza virus and Der p 2 (D2) allergen for allergen-specific immunotherapy of house-dust mite allergy (HDM). MAIN METHODS: H1sD2 chimera and D2 allergen were produced by genetic engineering in E. coli. Recombinant antigens were extracted from inclusion bodies by urea, then refolded and purified by immobilized- metal affinity chromatography (IMAC). Purity was verified by 2D-PAGE and secondary structures were assessed by CD spectroscopy. IgE reactivity of H1sD2 and D2 was tested in western blot with sera from 8 persons with clinical history of HDM allergy. Immunogenicity of H1sD2 and D2 were analyzed in Balb/c mice. Cytokine profile was analyzed by ELISA after stimulation of mouse spleen cells with H1sD2 and D2. Leukocyte population abundance of cells isolated from spleen and lymph node was assessed by flow cytometry. KEY FINDINGS: Purified recombinant proteins H1sD2 (42 kDa) and D2 (15 kDa) revealed well defined secondary structures, and preserved IgE reactive epitopes. Analysis of supernatants of mouse spleen cells after stimulation with H1sD2 and D2, revealed a qualitatively different cytokine profile from H1sD2 immunized mouse cells (increase in IL10). CD8+ cells were decreased in the lymph node of D2 immunized mice, whereas H1sD2 immunization led to an increase of CD8+ cells in both the lymph node and the spleen. SIGNIFICANCE: H1sD2 chimera attenuates Der p 2-inherent Th2 response and directs the immune response toward Th1 and Treg phenotype.

Asunto(s)

Alérgenos , Antígenos Dermatofagoides , Proteínas de Artrópodos , Hemaglutininas , Animales , Humanos , Ratones , Alérgenos/metabolismo , Alérgenos/uso terapéutico , Antígenos Dermatofagoides/genética , Antígenos Dermatofagoides/metabolismo , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/metabolismo , Epítopos/metabolismo , Escherichia coli/inmunología , Ingeniería Genética/métodos , Hemaglutininas/genética , Hemaglutininas/metabolismo , Hipersensibilidad/inmunología , Inmunoglobulina E/inmunología , Inmunoterapia/métodos , Ratones Endogámicos BALB C , Orthomyxoviridae/metabolismo , Pyroglyphidae/inmunología , Proteínas Recombinantes/genética

RESUMEN

BACKGROUND AND AIMS: Mucosal gene expression have not been fully enlightened in inflammatory bowel disease (IBD). Aim of this study was to define IL23A, IL17A, IL17F and TLR9 expression in different IBD phenotypes. METHODS: Evaluation of mRNA levels was performed in paired non-inflamed and inflamed mucosal biopsies of newly diagnosed 50 Crohn's disease (CD) and 54 ulcerative colitis (UC) patients by quantitative real-time PCR analysis. RESULTS: IL17A and IL17F expression levels were significantly increased in inflamed IBD mucosa. Inflamed CD ileal and UC mucosa showed increased IL23A, while only inflamed CD ileal samples showed increased TLR9 mRNA level. Correlation between analysed mRNAs levels and endoscopic and clinical disease activity were found in UC, but only with clinical activity in CD. CONCLUSION: Both CD and UC presented expression of Th17-associated genes. Nevertheless, expression profiles between different disease forms varies which should be taken into account for future research and therapeutics strategies.

Asunto(s)

Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Interleucina-17/genética , Subunidad p19 de la Interleucina-23/genética , Receptor Toll-Like 9/genética , Adulto , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/metabolismo , Colon/inmunología , Colon/metabolismo , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/metabolismo , Estudios Transversales , Femenino , Perfilación de la Expresión Génica , Humanos , Íleon/inmunología , Íleon/metabolismo , Interleucina-17/inmunología , Subunidad p19 de la Interleucina-23/inmunología , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Serbia , Transducción de Señal , Receptor Toll-Like 9/inmunología

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology in which genetic factors contribute to development of disease. Single nucleotide polymorphisms (SNPs) in multidrug resistance 1 (MDR1) gene encoding transporter P-glycoprotein have been associated with IBD, but their role in disease susceptibility remains unclear. Therefore, the aim of this study was to investigate the association of three MDR1 polymorphisms, C1236T (rs1128503), G2677T/A (rs2032582) and C3435T (rs1045642), with Serbian IBD patients. METHODS: A total of 206 IBD patients, 107 Crohn's disease (CD) and 99 ulcerative colitis (UC), and 255 healthy controls were included in the study. All subjects were genotyped using TaqMan SNP genotyping assays. Comparisons between the groups were performed using the Pearson Chi-square test. False discovery rate according to Benjamini-Hochberg procedure was applied to adjust for multiple comparisons. RESULTS: Carriers of T allele of all three MDR1 SNPs were more common in UC patients compared to healthy controls, suggesting predisposing role of T allele of these SNPs in UC pathogenesis. Consistently, TT genotype of C1236T and TTT haplotype were also found more frequently in UC patients. On the other hand, C allele and CC genotype of C1236T and C3435T, as well as G allele and GG genotype of G2677T/A were more frequent in healthy subjects, implying protective role of these variants in UC. Likewise, CGC haplotype and CGC/CGC diplotype were more frequent in controls. Contrary to UC, no statistical difference was observed between CD patients and controls in any of the SNPs analyzed. CONCLUSION: MDR1 gene variants and haplotypes were associated with UC in Serbian IBD patients, further supporting their potential role in susceptibility to UC.

Asunto(s)

Colitis Ulcerosa/genética , Predisposición Genética a la Enfermedad , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Anciano , Estudios de Casos y Controles , Enfermedad de Crohn/genética , Femenino , Frecuencia de los Genes , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Serbia , Adulto Joven

RESUMEN

OBJECTIVES: The aim of the study was to evaluate associations between inflammatory bowel disease (IBD) presentation and variants in NOD2, TLR4, TNF-α, IL-6, IL-1ß, and IL-RN genes in order to identify possible environmental factors that may affect IBD occurrence, investigate potential predictors for surgical treatment of IBD, and correlate the presence of granulomas in biopsy specimens with clinical characteristics of Crohn's disease (CD) patients. PATIENTS AND METHODS: We genotyped 167 IBD patients using PCR-based methodology and tested for disease genotype-phenotype associations. RESULTS: In CD patients ileal localization of disease was more frequent in NOD2 variant carriers. Ileal CD was associated with IL-6 GC+CC genotypes, identifying C allele as a possible marker of increased risk for ileal CD. In CD patients a positive family history for IBD was related to earlier onset of disease, higher risk for CD-related surgery, and appendectomy. CD patients who are TLR4 299Gly carriers are at higher risk for surgery at onset of the disease compared with TLR4 299Asp variant carriers. The presence of granuloma in biopsy specimens was more frequent in patients in whom a diagnosis of CD was made during emergency surgery. Multivariate analysis showed that CD carriers of the 299Gly allele had a 4.6-fold higher risk for emergency surgery before CD diagnosis is established compared with noncarriers, suggesting an aggressive disease course. Granuloma in endoscopic biopsies is detected 5.4-fold more frequently in patients treated surgically at the time of diagnosis. CONCLUSION: Genetic variants together with epidemiological and clinical data of IBD patients could potentially be used as predictors of the disease course.

Asunto(s)

Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/genética , Variación Genética , Adulto , Biopsia , Distribución de Chi-Cuadrado , Enfermedad de Crohn/diagnóstico , Estudios Transversales , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Granuloma/patología , Humanos , Íleon/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Fenotipo , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo

RESUMEN

Obesity is a growing problem worldwide and disorders associated with excess body fat including the metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular disease and malignant neoplasms are becoming a major cause of morbidity and mortality. Over the past decade, a vast amount of research has furthered our understanding of non-alcoholic fatty liver disease; however, only recently pancreatic fat infiltration is coming to the forefront of investigation. Termed non-alcoholic fatty pancreas disease (NAFPD), it is becoming evident that it has important associations with other diseases of obesity. It appears to arise as obesity progresses and after an initial phase of pancreatic hypertrophy and hyperplasia, fatty infiltration becomes apparent. Various studies have demonstrated that NAFPD may exacerbate the severity of acute pancreatitis, promote pancreatic dysfunction associated with insulin resistance and T2DM, and even have links to the development of pancreatic carcinoma, and therefore, it must be investigated in further detail.

Asunto(s)

Diabetes Mellitus Tipo 2/complicaciones , Síndrome Metabólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Obesidad/complicaciones , Páncreas/patología , Enfermedades Pancreáticas/etiología , Humanos , Hiperlipidemias , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/metabolismo , Obesidad/fisiopatología , Enfermedades Pancreáticas/metabolismo , Enfermedades Pancreáticas/fisiopatología , Factores de Riesgo

RESUMEN

Objective: Keeping in mind the rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the need to establish noninvasive tests for its detection, the aim of our study was to investigate whether platelet count (PC), mean platelet volume (MPV), and platelet distribution width (PDW) can predict the presence of liver fibrosis in this group of patients. Methods: In 98 patients with NAFLD and 60 healthy volunteers, complete blood counts with automated differential counts were performed and values of PC, PDW, MPV, and PCT were analyzed. Results: Patients with NAFLD had lower PC and higher MPV, PCT, and PDW compared to the controls (P < 0.05). When NAFLD group was stratified according to severity of liver fibrosis, there was a statistically significant difference in the average values of PDW and PC between the groups (P < 0.05). Conclusion: Patients with NAFLD have significantly higher values of PCT, PDW, and MPV when compared to the healthy controls. Further studies are needed to establish their potential use for prediction of the degree of liver steatosis and fibrosis in NAFLD patients.

Asunto(s)

Índices de Eritrocitos , Cirrosis Hepática/diagnóstico , Volúmen Plaquetario Medio/estadística & datos numéricos , Enfermedad del Hígado Graso no Alcohólico/sangre , Recuento de Plaquetas/estadística & datos numéricos , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Sensibilidad y Especificidad

RESUMEN

Inflammatory bowel disease (IBD), manifesting as Crohn's disease (CD) and ulcerative colitis (UC), is characterized by recurring episodes of inflammation in gastrointestinal tract, in which aberrant production of regulatory cytokine interleukin-10 (IL-10) presumably plays important role. Single nucleotide polymorphisms (SNPs) that affect IL-10 production, such as rs1800896 (G/A) at position -1082 and rs1800871 (C/T) at position -819 in the promoter region of the IL10 gene, have been associated with CD and/or UC, but the results were inconsistent. Another SNP that may alter IL-10 production, rs3024505 (C/T) located immediately downstream of the IL10 gene has been recently identified. T allele of rs3024505 was associated with both UC and CD in Western populations, but the studies from East European countries are lacking. Therefore, our aim was to assess the association of rs3024505, rs1800896 and rs1800871 with Serbian IBD patients. To this end, 107 CD and 99 UC patients and 255 healthy controls were genotyped. As a result, T allele of rs3024505 was associated with CD at allelic, genotypic (GT genotype) and haplotypic (GCCT haplotype) level, suggesting potential role of this variant in susceptibility to CD. In contrast, CD patients carrying C allele of rs3024505 had significantly increased risk of anemia and stricturing/penetrating behavior. No association was observed between rs3024505 and UC or SNPs in IL10 promoter region and any form of IBD. In conclusion, rs3024505 SNP flanking the IL10 gene is associated with susceptibility and severity of disease in Serbian CD patients, further validating its role as a potential biomarker in IBD.

Asunto(s)

Enfermedad de Crohn/genética , Predisposición Genética a la Enfermedad , Interleucina-10/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Colitis Ulcerosa/genética , Femenino , Frecuencia de los Genes , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad , Serbia , Adulto Joven

RESUMEN

OBJECTIVE: Research on inflammatory bowel disease (IBD) has highlighted genes involved in the regulation of inflammatory responses as contributors to disease pathogenesis. This study aimed to evaluate the associations between IBD and variations in NOD2, TLR4, TNF-α, IL-6, IL-1ß and IL-1RN genes, and to use the genetic data obtained in predictive modeling. METHODS: A total of 167 IBD patients and 101 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Using the genotype data attained as the input to various classification algorithms, IBD prediction models were designed. The area under the receiver operating characteristic curve (AUROC) was used to measure their performance. RESULTS: Significant associations were found between Crohn's disease (CD) and minor NOD2 variants, as well as TLR4 299Gly, TNF-α G-308A, IL-6 G-174C and IL-1RN VNTR A2 variants, while ulcerative colitis (UC) was associated only with IL-1RN VNTR A2 variants. CD and UC showed highly significant difference in the allelic distribution of TNF-α G-308A, where the A allele was found to be related to CD, and the G allele to UC. A combined effect of patients' gender and TLR4 variants was observed among CD patients. When all analyzed genotype and gender data were used, prediction performance achieved a maximum AUROC of 0.690 for CD and 0.601 for UC dataset. CONCLUSION: Variations in the genes involved in immune regulation are genetic factors of importance in IBD susceptibility that could potentially be used as predictors of disease development.

Asunto(s)

Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Predisposición Genética a la Enfermedad/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Biomarcadores/sangre , Estudios de Casos y Controles , Colitis Ulcerosa/sangre , Enfermedad de Crohn/sangre , Femenino , Marcadores Genéticos , Pruebas Genéticas , Genotipo , Humanos , Proteína Antagonista del Receptor de Interleucina 1/sangre , Proteína Antagonista del Receptor de Interleucina 1/genética , Interleucina-1beta/sangre , Interleucina-1beta/genética , Interleucina-6/sangre , Interleucina-6/genética , Péptidos y Proteínas de Señalización Intracelular/sangre , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite , Proteína Adaptadora de Señalización NOD2/sangre , Proteína Adaptadora de Señalización NOD2/genética , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Valor Predictivo de las Pruebas , Serbia , Factores Sexuales , Receptor Toll-Like 4/sangre , Receptor Toll-Like 4/genética , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Población Blanca/genética , Adulto Joven

RESUMEN

INTRODUCTION: Calprotectin is a cytoplasmatic protein of neutrophilic granulocytes and it is an established marker for the assessment of localized intestinal inflammation. AIM: To explore correlation between values of fecal calprotectin and degree of liver cirrhosis and hepatic encephalopathy. METHODS: We included 60 patients with liver cirrhosis and 37 healthy patients as controls. Patients revealing other causes of abnormal calprotectin results (gastrointestinal bleeding or inflammatory bowel disease) were excluded. The degree of liver insufficiency was assessed according to the Child-Pugh classification and Model of End Stage Liver Disease (MELD), and degree of hepatic enceph- alopathy by West-Haven criteria, serum concentration of ammonium ion and the number connection test. RESULTS: The mean value of fecal calprotectin in patients with liver cirrhosis was 189.1 ± 168.0 µg/g, and 35.0 ± 26.0 µg/g in the control group, respectively. We have confirmed significantly higher fecal calprotectin in patients with cirrhosis (p < 0.001). There were no significant differences in values of fecal calprotectin between the patients with different stages of liver cirrhosis according to Child-Pugh classification and MELD score (p > 0.05). We observed statistically significant difference comparing fecal calprotectin by West-Haven criteria of hepatic encephalopathy (p < 0.001), while there were no correlation with the number connection test and serum concentration of ammonium ion (p > 0.05). CONCLUSION: We confirmed significantly higher values of fecal calprotectin in patients with liver cirrhosis, especially in hepatic encephalopathy according to West-Haven criteria.

Asunto(s)

Encefalopatía Hepática/metabolismo , Encefalopatía Hepática/patología , Complejo de Antígeno L1 de Leucocito/metabolismo , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Adulto , Anciano , Biomarcadores/metabolismo , Estudios de Casos y Controles , Estudios Transversales , Heces , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad