Juvenile idiopathic arthritis (JIA) is an umbrella term for seven distinct chronic immune-mediated diseases. Disease-modifying anti-rheumatic drugs (DMARD) are used to treat the underlying joint ...inflammation as well as extra-articular manifestations. Immunosuppression is a considerable side effect of the drugs. The main goal of this study was to investigate the effect of different JIA therapies on leukocyte subpopulations, which play a role in immune-defense. Three study groups were established. The first group consisted of JIA patients treated with methotrexate solely, the second one received a combination of methotrexate (MTX) and adalimumab (ADA). The control group was made up of the patients' healthy siblings. A total of 63 children were recruited. Fourty-one children with JIA and 22 healthy controls were included in the study. The absolute number of CD3+ T-cells was significantly elevated in patients treated with biological therapy compared to healthy controls (p2 = 0.017). In contrast, the number of CD56+ natural killer cells was significantly lower in children receiving biological therapy in comparison with healthy donors (p2 = 0.039). A significant alteration was also demonstrated between patients treated with MTX and MTX/ADA group concerning CD 19+ B-cells (p3 = 0.042). This is the first study that demonstrates significant alterations in the number of B-cells and T-cells with a relative decrease of NK-cell ratios in JIA patients receiving different DMARD therapy.
NCT03833271. 21.01.2019.
: Psoriasis is a chronic inflammatory systemic disease that affects 2% of the population and is associated with an important physical and physiological burden. About 0.5-2% of psoriatic cases onset ...during the pediatric age range, and often it's not diagnosed until adulthood. Adalimumab is an antitumor necrosis factor monoclonal antibody approved for use in children in 2008 and now it was used in several diseases in rheumatology, gastroenterology, and in dermatology.
: The purpose of this article was to summarize what has been described in the literature so far, about safety in the use of adalimumab in pediatric psoriasis. The presented data was extrapolated from a literature review from PubMed searches (using words 'pediatric psoriasis,' 'adalimumab children,' 'adalimumab safety,' 'pediatric psoriasis treatment,' 'adalimumab clinical trial'), treatment guidelines, and reports from European and United States regulatory agencies.
: Actually there are some biologic agents for the treatment of pediatric psoriasis, but the lack of safety data from controlled trials is evident. The safety data on the use of adalimumab in pediatric psoriasis was taken from long-term studies in the adult population. These studies confirm the data on the safety of the drug as it is also supported by several works on real-life.
•In PC TNF-α, EGF, IL-1α, IL-1RII and IL-1Ra were observed in epithelial cells.•Increased EGFR and reduced IL-1α/TGF-B correlated with biochem. progression.•IL-1α and intensity TGFBRI predicted ...biochemical progression.•Expression of TGF-B, IL-1α, TGFBRI and TGFBRII as prognostic markers for PC.
This work is focused on finding new markers that complement or diagnoses currently used towards improving knowledge histological and statistical aspects that allow us to predict the local stage carcinomas and to identify and understand all the factors related to the progression of this disease.
Prostates were obtained from: normal prostates from 20 men, diagnosis of BPH (Benign Prostatic Hyperplasia) from 35 men and prostate cancer from 86 men. We studied the behavior of cytokines that have been implicated in inflammatory processes: TNF-alfa, IL-6, IL-1, EGF and TGF-B. Expression of these cytokines and its receptors was analyzed by immunohistochemistry. Spearman’s test, Kaplan-Meier curves, univariate and multivariate Cox proportional hazard regression analyses were performed.
Spearman’s analysis showed that there was at least one correlation between TGFB-B, IL-6, gp-130, IL-1B, IL-1R, IL-1RII and clinic pathological feature (preoperative serum PSA, clinical t stage, pathological t stage, positive surgical margins, biochemical progression, survival). Immunostaining score was correlated with some of the clinicopathological feature. In Cox multivariate analysis between the prognostic variables (pathological T stage, Gleason score and lymph node) and immunohistochemical parameters (TGF-B, IL-1a, intensity TGFBRI and intensity TGFBRII) only the expression of IL-1a was retained as independent predictors of biochemical progression after radical prostatectomy.
Our results suggest a role for prostatic expression of TGF-B, IL-1a, TGFBRI and TGFBRII as prognostic markers for prostate cancer. The rational combination of novel agents directed toward the inactivation of TGF-B, IL-1a, TGFBRI and TGFBRII could disrupt complementary tumor cell proliferation pathways.
Tumour necrosis factor (TNF)-α plays an important role in inflammatory, infectious, and tumor processes, and it is closely related to the early stages of gastric cancer. It is a pro-inflammatory ...cytokine, produced not only by macrophages and monocytes but also by the lymphocytes, mast cells, neutrophils, keratinocytes, smooth muscle cells, and some tumor cell lines. Large amounts of TNF are released upon contact of macrophages, CD4 + T lymphocytes, and natural killer (NK) cells with lipopolysaccharides, bacterial products, and interleukin 1. TNF-alpha inducing protein (Tipa) is a unique carcinogenic factor of Helicobacter pylori, secreted into culture broth. The biological activities of TNF alpha and deletion mutant were studied. TNF alpha protein specifically binds to cell-surface nucleolin and then enters the gastric cancer cells, where TNF-a and chemokine gene expressions are induced by NF-jB activation. Nucleolin localizes on the surface of gastric cancer cells, and interaction between TNF alpha and cell-surface nucleolin causes a cancer-oriented microenvironment that increases the risk of gastric cancer. This paper discusses a mechanism of gastric cancer development and the clinical significance of tumor necrosis-alpha and carcinoembryonic antigen in gastric cancer.
Objectives: Primary - a study of the correlation between serum osteoprotegerin (OPG), and biomarkers of bone metabolism in patients with treatment-naive Graves' disease (GD). Secondary - serum level ...of OPG, TNF-alfa, and biomarkers of bone metabolism in patients three months after treatment of GD with methimazole (MMI). Materials and Methods: A total of thirty-five treatment-naive newly diagnosed GDs were recruited for the study, most of them female. All patients started with MMI for treatment and various blood parameters were measured at baseline and three months after treatment. Measurements: Serum calcium (Ca), phosphorus (P), bone-specific alkaline phosphatase (B-ALP), OPG, TNF-alfa, and urine deoxypyridinoline (U-DPD) along with serum-free T3 and T4, thyroid-stimulating hormone (TSH) and thyroid receptor antibody (TR-ab) were analysed at baseline and three months after MMI treatment. All the patients had euthyroid at three months of MMI treatment. Results: Mean serum OPG (0.94 ± 1.39 vs. 0.63 ± 0.27 ng/ml; P = 0.262) level at baseline and after treatment with MMI did not show any significant change. Mean TSH level (0.207 ± 0.59 vs. 1.00 ± 1.95, P = 0.025) was significantly low at baseline than after treatment; FT4 (5.9 ± 5.22 v 1.77 ± 1.89 ng/dl; P < 0.001), FT3 (12.19 ± 6.91 vs. 4.99 ± 3.55 pg/ml; P < 0.001), and TNF-alfa values decreased significantly after treatment, however, PTH (58.09 ± 28.75 vs. 75.57 ± 41.50; P < 0.026) increased significantly after treatment. Discussion: There is no correlation of OPG with thyroid hormone profile, TSH, thyroid receptor antibody (TR-ab), and bone metabolic parameters such as serum Ca, P, B-ALP, TNF-alfa, and U-DPD in our study. Mean TNF-alfa decreased significantly (393.43 ± 270.473 vs. 139.34 ± 101.264 pg/ml; P = 0.001) level after treatment with MMI. TNF-alfa was positively correlated with TR-ab (r = 0.374; P = 0.027) and B-ALP (r = 0.388; P = 0.021). Conclusion: The bone turnover marker in GD seems to be mediated other than OPG. We observed an increase in circulating TNF-alfa in GD with a significant decrease after treatment. TNF-alfa could be a marker of GD activity as evidenced by a close positive correlation with TR-ab, a sensitive marker of GD autoimmunity. TNF-alfa could be a factor associated with bone turnover markers in GD despite its euthyroid state.
Inflammatory bowel disease (IBD) is a chronic and incurable entity. Therapy with anti-TNF-α agents was the first biologic therapy approved in Mexico for IBD. New biologic agents, such as vedolizumab ...and ustekinumab, have recently been added, as have small-molecule inhibitors.
To update the biologic therapeutic approach to IBD in Mexico with new anti-TNF-α agents and novel biologics whose mechanisms of action induce and maintain remission of Crohn’s disease and ulcerative colitis (UC).
Mexican specialists in the areas of gastroenterology and inflammatory bowel disease were summoned to participate. The consensus was divided into 3 modules, with 49 statements. The Delphi method was applied, sending the statements to all participants to be analyzed and edited, before the face-to-face meeting. During said meeting, the clinical studies were shown, emphasizing the level of clinical evidence, and the final discussion and voting round on the level of agreement of all the statements was conducted.
In this second Mexican consensus, recommendations are made for new anti-TNF-α agents, such as golimumab, new biologics with other mechanisms of action, such as vedolizumab and ustekinumab, as well as for the small-molecule inhibitor, tofacitinib.
The updated recommendations focus on patient-reported outcomes, biologic therapy, small-molecule inhibitors, and the safety aspects of each of the drugs.
La enfermedad inflamatoria intestinal (EII) es una entidad crónica e incurable. La terapia con agentes anti-TNF alfa fue la primera terapia biológica aprobada en México en EII. Recientemente han aparecido nuevos agentes biológicos como el vedolizumab y ustekinumab así como inhibidores de moléculas pequeñas.
Actualizar el enfoque terapéutico biológico de la EII en nuestro país con nuevos agentes anti-TNF alfa y nuevos mecanismos de acción para la inducción y mantenimiento de remisión de la enfermedad de Crohn y colitis ulcerosa crónica idiopática (CUCI).
Se invitaron a especialistas de la República Mexicana de las áreas de Gastroenterología y Enfermedad Inflamatoria Intestinal. Se dividió el consenso en 3 módulos, con 49 enunciados. Se aplicó el método de panel Delphi, para ello se envió las preguntas previó a la reunión a todos los participantes para que fueran editadas y ponderadas. Durante la reunión presencial se mostraron los estudios clínicos dando énfasis al nivel de evidencia clínica y se llevó a cabo la discusión y votación final del grado de acuerdo en todos los enunciados.
Es el segundo consenso mexicano en donde se establecen las recomendaciones para nuevos anti-TNF alfa como el golimumab y otros mecanismos de acción como vedolizumab, ustekinumab y tofacitinib.
Las recomendaciones actualizadas se centran en los resultados informados por los pacientes, la terapia biológica, los inhibidores de moléculas pequeñas y los aspectos de seguridad de cada uno.
Colorectal cancer is one of the most prevalent cancers worldwide. There is a great interest and need to find simple, inexpensive, and minimally invasive diagnostic tests. The aim of the study was to ...analyze the salivary concentrations of chemerin, α-defensin 1, and TNF-α in colorectal cancer (CRC) patients and in a healthy control group. The concentration of these proteins was simultaneously determined in the serum of subjects. We also aimed to assess the correlation of these results and selected clinicopathological features. This prospective study was comprised of 39 CRC patients and 40 control group patients. Salivary and serum concentrations were determined by enzyme immunoassays. The salivary and serum concentrations of chemerin, α-defensin 1, and TNF-α were significantly higher in cancer patients compared to the control group. No correlation was found between concentrations of the proteins and the clinical stage of cancer and tumor location. The ROC curve analysis showed that although salivary concentrations of all proteins showed 100% sensitivity and 100% specificity, serum concentrations of the analyzed proteins were characterized by 100% sensitivity and over 90% specificity. The assessment of chemerin, α-defensin 1, and TNF-α concentrations in saliva seem to have great potential as quick and useful biomarkers in the early diagnosis of CRC.
Abstract
Objective
In this study, we aimed to investigate the changes in the levels of oxidative stress and antioxidant enzymes on the mandibular bone caused by the expression of aquaporin-1 and ...aquaporin-3 proteins.
Material and method
14 Balb/C white mice were divided into two groups of seven, based on whether they are young or old. Mandibular tissue samples were taken for biochemical and histological analysis.
Results
Findings of our study has shown that, AQP-1 and AQP-3 immunoreactivity significantly decreased in mandibular bone tissues of aged mice in comparison to younger mice (p < 0.05). MDA and AOPP levels, which are the indicators of oxidative stress, increased in elderly mice and antioxidant defense system SOD enzyme activity was decreased (p < 0.05). The TNF-α cytokine level, which is the indicator for inflammations, was found to be higher in older mice than in young mice (p < 0.05).
Conclusion
As a result, it was observed that cellular damage, disruption in water – electrolyte balance and increased inflammation that occur during the natural process of aging had caused serious and irreversible disturbances.
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