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Arq. gastroenterol ; 58(1): 107-113, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1248984


ABSTRACT BACKGROUND: The rates of postoperative endoscopic recurrence (PER) in patients with Crohn's disease (CD) are consistent. Anti-TNF therapy has been increasingly used in the postoperative setting, despite the lack of robust data in the literature on the measurement of trough levels and consequences of their use. OBJECTIVE: The aim of this review was to assess trough levels of infliximab (IFX) in CD patients after ileocolonic resections in correlation with the presence of PER. METHODS: We searched for studies that evaluated trough levels of IFX in patients with CD, who underwent ileocaecal resections, and correlated them with the presence of PER. We used MEDLINE through PubMed and CENTRAL Cochrane library databases, and after matching the inclusion criteria, the studies were methodologically evaluated with qualitative analysis of the data. RESULTS: A total of 155 studies were initially identified in the databases search and only four matched the inclusion criteria. They comprised one prospective cohort study, one randomized controlled trial and two retrospective cohort studies, the last one performed in pediatric patients. This evidence suggested the correlation of PER with low trough levels of IFX and the presence of antibodies to the drug. The quality of the evidence generated varied from very low to high, due to the heterogeneity found between the studies and the risks of bias that were identified. CONCLUSION: Low levels of IFX and the presence of antibodies to the drug were directly associated with increased PER rates in patients with CD, who underwent ileocolonic resections. Controlled and randomized clinical trials with adequate methodological quality are warranted to confirm the conclusions from this systematic review.

RESUMO CONTEXTO: As taxas de recorrência endoscópica pós-operatória em pacientes com doença de Crohn (DC) são significativas. A terapia anti-TNF é cada vez mais usada no cenário pós-operatório, apesar da escassez de dados na literatura sobre dosagem de níveis séricos e anticorpos da droga. OBJETIVO: Realizou-se uma revisão sistemática com o intuito de se avaliar níveis séricos de infliximabe (IFX) em pacientes com DC submetidos a ileocolectomia e correlacionar com a presença ou não de recorrência endoscópica da doença. MÉTODOS: Buscou-se por estudos que avaliaram o nível sérico do IFX em pacientes com DC, submetidos a ileocolectomias, correlacionando-os à presença de recorrência endoscópica pós-operatória. Utilizou-se as bases de dados MEDLINE via PubMed e CENTRAL Cochrane Library, e após atingirem os critérios de inclusão, os estudos foram avaliados metodologicamente e foi realizada análise qualitativa dos dados. RESULTADOS: Um total de 155 estudos foram identificados e apenas quatro atingiram os critérios de inclusão. Um era estudo de coorte prospectivo, o segundo era um ensaio clínico randomizado e dois eram estudos de coortes retrospectivas, sendo o último exclusivamente em pacientes pediátricos. As evidências encontradas tendem a confirmar a correlação da recorrência endoscópica a baixos níveis séricos de IFX e presença de anticorpos anti-droga. A qualidade da evidência gerada variou de muito baixa a alta, devido à heterogeneidade encontrada entre os estudos e o risco de viés identificado. CONCLUSÃO: Baixos níveis séricos do IFX e presença de anticorpos contra a droga estão associados a probabilidade aumentada de recorrência endoscópica pós-operatória nos pacientes com DC submetidos a ileocolectomias. Ensaios clínicos controlados e randomizados com adequada qualidade metodológica são necessários para confirmar as conclusões desta revisão.

Humans , Child , Crohn Disease/surgery , Crohn Disease/drug therapy , Prospective Studies , Retrospective Studies , Tumor Necrosis Factor-alpha , Infliximab/therapeutic use
Article in Chinese | WPRIM | ID: wpr-879445


OBJECTIVE@#To investigate the expression and clinical significance of receptor interacting protein serine-threonine kinases 1 (RIPK1) in the nucleus pulposus of patients with lumbar disc herniation (LDH).@*METHODS@#Nucleus pulposus tissue specimens of 40 patients with LDH patients underwent surgical treatment from January 2016 to January 2018 as the case group, and nucleus pulposus tissue specimens of 30 patients with lumbar spine fracture underwent surgical treatment at the same time as the control group. The expression of RIPK1 mRNA and protein of receptor interaction were detected by polymerase chain reaction (PCR) and Western blot, respectively. The expression of RIPK1 protein in the nucleus pulposus were detected by immunohistochemical staining. The concentrations of RIPK1 and tumor necrosis factor-α (TNF-α) in nucleus pulposus were detected by ELISA method. The relationship between the concentrations of RIPK1, TNF-α in nucleus pulposus and the Pearce grade of LDH patients was analyzed by one-way ANOVA. The correlation between RIPK1 and TNF-α was analyzed by Pearson.@*RESULTS@#RIPK1 was weakly positively expressed in nucleus pulposus of control group, and RIPK1 protein was positively or strongly positively expressed in case group. The expression of RIPK1 mRNA in nucleus pulposus of case group was higher than that of control group (@*CONCLUSION@#The expression levels of RIPK1 mRNA and protein in the intervertebral disc tissues of LDH patients are higher than those of normal intervertebral disc tissues, and increased with the increase of Pearce grade, which may be an important factor involved in LDH inflammatory disease.

Humans , Intervertebral Disc/metabolism , Intervertebral Disc Degeneration , Intervertebral Disc Displacement/genetics , Nucleus Pulposus , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Tumor Necrosis Factor-alpha/metabolism
Article in Chinese | WPRIM | ID: wpr-879137


The aim of this paper was to investigate the preventive and therapeutic effects of Xiaoer Feike Granules(XEFK) on chronic bronchitis in rats and its mechanism. Except for 10 rats in the blank group, the remaining 50 of the 60 SD rats were used to establish a model of chronic bronchitis induced by LPS. On the 22 nd day, the model rats were randomly divided into 5 groups according to their body weight, and administrated with purified water, Keteling Capsules 0.11 g·kg~(-1), XEFK 3.2, 1.6 and 0.8 g·kg~(-1)(the dosing concentrations were 0.32, 0.16, 0.08 g·mL~(-1), respectively). These rats took the corresponding drug orally once a day, for consecutive 21 days. The rats were anesthetized 1 hour after the last administration, and the lavage bronchus and alveoli were collected. Then, after the fixation of the smear, neutrophils were counted microscopically, and the contents of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in the bronchoalveolar lavage fluid(BALF) were detected by colorimetric method. Flow cytometry was used to detect the content changes of T cell subsets CD4~+, CD8~+, CD4~+/CD8~(+ )in serum. Hemorheology related indexes were detected by automatic hemorheology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-2, IL-6 and IL-10 in serum. The expression of TNF-α and IL-10 mRNA in lung was detected by Real-time quantitative PCR(RT-qPCR). HE staining was used to observe the pathological changes in the bronchitis tissues. Compared with the model group, XEFK high and medium dose groups could significantly reduce the contents of neutrophils and MDA in bronchial lavage fluid, and increase the activities of GSH-Px and SOD in BALF, and repair the chronic inflammatory cell infiltration and lymphoid tissue hyperplasia in the bronchial mucosal layer and submucosal layer. The high-dose group could reduce the plasma viscosity of rats, but there was no statistical difference in other hemorheological indexes. CD4~+, CD8~+, CD4~+/CD8~+, IL-2 and IL-10 contents in each dose group were significantly increased, and TNF-α, IL-1β and IL-6 contents were significantly decreased in serum. Each dose group could significantly down-regulate the expression level of TNF-α mRNA in the lung and increase the expression of IL-10 mRNA. XEFK could reduce lipid peroxidation, increase the content of peripheral blood T cell subsets, regulate the release and secretion of inflammatory factors, and repair the morphological and pathological changes of bronchial tissue. Its mechanism might be related to the improvement of inflammatory response and the enhancement of immune function.

Animals , Bronchitis, Chronic/drug therapy , Drugs, Chinese Herbal/pharmacology , Glutathione Peroxidase , Lipopolysaccharides , Lung , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha
Article in Chinese | WPRIM | ID: wpr-879076


This study aims to investigate the preventive effect of Dendrobium officinale in LPS-induced intestinal mucosal damage. Forty SPF-grade C57 BL/6 J male mice were randomly divided into normal group(NC), model group(LPS), and two superfine powder groups of Dendrobium officinale(DOF)(DOF-L, 0.30 g·kg~(-1)and DOF-H, 0.60 g·kg~(-1), respectively), with 10 mice in each group. DOF superfine powder suspension was given via oral administration to mice for 7 days, while the mice in NC and LPS groups received the same volume of saline for 7 days. On the eighth day, the mice in LPS group and DOF treatment groups were injected with LPS(5 mg·kg~(-1)) by intraperitoneal injection to establish the intestinal mucosal injury model, while the mice in NC group were injected with the same volume of sterile saline in the same manner. Six hours after injection with LPS or saline, plasma and the intestinal tissue were collected. The diamine oxidase(DAO) and D-lactate levels in plasma were detected with a biochemical method. The levels of proinflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma were detected by ELISA. The histomorphology and ultrastructure of mouse ileum tissues were observed by hematoxylin-eosin(HE) staining in optical microscope and transmission electron microscope(TEM). The expression and distribution of tight junction(TJ) proteins claudin-1, occludin and F4/80 were detected by immunohistochemistry while the protein expression levels of Toll-like receptor 4(TLR-4) and nuclear factor kappa B p65(NF-κB p65) in jejunum were detected by Western blot. The experimental results showed that continuous intragastric administration of D. officinale superfine powder for 7 days obviously alleviated the damage and ultrastructural changes of intestinal mucosa induced by LPS; significantly decreased DAO and D-lactate levels in plasma in model group(P<0.05); up-regulated the protein expression of claudin-1 and occludin in ileum tissues; down-regulated the protein expression of TLR-4 and NF-κB p65 in jejunum tissues(P<0.01); significantly decreased TNF-α and IL-6 levels in plasma(P<0.05); and decreased the infiltration of F4/80~+ macrophage cells. Our results suggested that D. officinale had significant protective effects on LPS-induced intestinal mucosal damage and reduced intestinal permeability. The mechanism might be related to its effects of inhibiting inflammation via TLR-4/NF-κB p65, and up-regulating the expression of tight junction proteins.

Animals , Dendrobium , Intestinal Mucosa , Lipopolysaccharides , Male , Mice , NF-kappa B , Powders , Tumor Necrosis Factor-alpha/genetics
Article in Chinese | WPRIM | ID: wpr-879075


Dendrobii officinalis, with a definite effect of nourishing Yin and clearing heat, has been a folk habit for drinking after being mixed with water. Because its superfine powder has the advantages of high dissolution and convenient drinking, we observed the effect of D. officinalis superfine powder on metabolic hypertension model rats and its possible mechanism in this experiment, which can be used as a reference for its clinical application for hypertension. The overeating greasy-induced metabolic hypertension model was established with high-fat, high-sugar and high-purine diet. These rats were orally administered with 400 mg·kg~(-1) and 200 mg·kg~(-1) of D. officinalis superfine powder for 20 consecutive weeks. During this period, blood pressure, blood lipid, blood glucose, insulin and other related indexes of glucose and lipid metabolism were monitored; the levels of lipopolysaccharide(LPS), C-reactive protein(CRP), interleukin 6(IL-6) and other inflammatory mediators were measured; the levels of nitric oxide(NO) and endothelin-1(ET-1) were detected, and the histomorphological and ultrastructural changes of aorta were observed. In addition, the expression of LPS/TLR4 pathway-related molecules in aorta was determined. The results showed that long-term administration of D. officinalis superfine powder significantly reduced the levels of systolic blood pressure(SBP), diastolic blood pressure(DBP) and mean arterial pressure(MBP) in metabolic hypertension model rats, decreased the levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-c), glucose(Glu), and insulin(INS) levels in blood, increased the contents of high density lipoprotein cholesterol(HDL-c),decreased the LPS, CRP, IL-6 and ET-1 levels in blood and increased NO content. Furthermore, it improved the abnormality of aortic histomorphology and endothelial ultrastructure, and inhibited the protein expression of TLR4, myeloid differentiation factor(MyD88), IL-6, interleukin-1 β(IL-1β), and tumor necrosis factor-α(TNF-α) as well as mRNA expression of TNF-α and IL-1β in aorta. In conclusion, D. officinalis superfine powder may improve the abnormal function and structure of blood vessels by inhibiting the activation of LPS/TLR4 pathway, thus playing a role against metabolic hypertension.

Animals , Dendrobium/chemistry , Drugs, Chinese Herbal/pharmacology , Hyperphagia , Hypertension/drug therapy , Interleukin-6 , Powders , Rats , Tumor Necrosis Factor-alpha
Article in Chinese | WPRIM | ID: wpr-878992


The aim of this paper was to observe the effect of Xinfeng Capsules(XFC)-containing serum on the apoptosis and inflammation of fibroblast-like synoviocytes(FLS) in rheumatoid arthritis(RA) induced by tumor necrosis factor-α(TNF-α), so as to investigate the mechanism of XFC in the treatment of RA. RA-FLS immortalized cell line was established, and XFC drug-containing serum was prepared. CCK-8, ELISA, RT-qPCR, immunofluorescence and TUNEL were used to observe the effect of XFC-containing serum on RA-FLS apoptosis and inflammatory indexes. CCK-8 results showed that the optimal concentration and time of TNF-α on RA-FLS were 10 ng·mL~(-1) and 48 h, respectively; and the optimal concentration and time of XFC on RA-FLS were 6.48 mg·g~(-1) and 72 h, respectively. The results of ELISA showed that compared with RA-FLS group, the expressions of TNF-α, IL-1β, IL-6, IL-8 in TNF-α+RA-FLS group were significantly increased, while the expressions of IL-4 and IL-10 were significantly decreased(P<0.01); after intervention with XFC-containing serum, the expressions of TNF-α, IL-1β, IL-6, IL-8 were significantly decreased, whereas the expressions of IL-4 and IL-10 were significantly increased(P<0.01). The results of RT-qPCR showed that compared with RA-FLS group, the mRNA expressions of Fas, FasL, caspase-3, caspase-8, Bax, Bcl-X1 in TNF-α+RA-FLS group were significantly decreased, while the mRNA expression of Bcl-2 was significantly increased(P<0.001); after intervention with XFC-containing serum, the mRNA expressions of Fas, FasL, caspase-3, caspase-8, Bax, Bcl-X1 were significantly increased, whereas the mRNA expression of Bcl-2 was significantly decreased(P<0.01). The results of immunofluorescence showed that compared with RA-FLS group, the protein expressions of caspase-3 and Bax in TNF-α+RA-FLS group was significantly lower than those in RA-FLS group(P<0.05); after intervention with XFC-containing serum, the protein expressions of caspase-3 and Bax were significantly increased, whereas the protein expression of Bcl-2 was significantly decreased(P<0.05). TUNEL results showed that compared with RA-FLS group, the apoptosis of TNF-α+RA-FLS group was decreased(P<0.05); after intervention with XFC-containing serum, the apoptosis was significantly increased(P<0.05). One of the mechanisms of XFC in the treatment of RA is to promote the apoptosis of RA-FLS and inhibit its inflammatory reaction.

Apoptosis , Arthritis, Rheumatoid/genetics , Capsules , Cells, Cultured , Drugs, Chinese Herbal , Fibroblasts , Humans , Inflammation , Synovial Membrane , Synoviocytes , Tumor Necrosis Factor-alpha/genetics
Article in English | WPRIM | ID: wpr-878441


OBJECTIVES@#To study the effect and mechanism of low-level laser irradiation (LLLI) on lipopolysaccharide (LPS)-induced inflammatory injury of human periodontal ligament fibroblasts (hPDLFs).@*METHODS@#hPDLFs were inoculated into well plates and randomly divided into the normal group, LPS group, and LPS+LLLI group. The cells in the normal group were cultured in conventional medium. The hPDLFs in the LPS and LPS+LLLI groups were cultured in RPMI1640 medium containing 1 mg·L@*RESULTS@#Compared with the normal group, the LPS group showed increased apoptosis rate of hPDLFs and intracellular free Ca@*CONCLUSIONS@#LLLI has a protective effect on the inflammatory injury of hPDLFs induced by LPS, and the effect is most obvious when the irradiation intensity is 4 J·cm

Cells, Cultured , Fibroblasts , Humans , Interleukin-1beta , Lasers , Lipopolysaccharides , Periodontal Ligament , Tumor Necrosis Factor-alpha
Article in English | WPRIM | ID: wpr-880649


OBJECTIVES@#Human periodontal ligament cells (hPDLCs) are important source of periodontal tissue reconstruction. Under chronic inflammation, the multi-directional differentiation potential and chemotaxis in hPDLCs are decreased. Therefore, inhibiting inflammatory microenvironment and improving the functional characteristics of stem cells can better promote periodontal tissue reconstruction. This study was to investigate the effect of astaxanthin (AST) on lipopolysaccharide (LPS)-induced inflammation in hPDLCs and the underlying mechanisms.@*METHODS@#hPDLCs were isolated and cultured in vitro, and vimentin and keratin immunocytochemical staining were used to identify hPDLCs. CCK-8 assay was used to measure the effects of AST (1, 5, 10, 20, 50, 100, and 200 μmol/L) on proliferation of hPDLCs. Quantitative RT-PCR (RT-qPCR) and ELISA were used to measure the mRNA and protein expression of inflammatory factors (IL-6, IL-1β, and TNF-α) in the control (Con) group, the LPS group, and the LPS+AST (5, 10, 20, and 50 μmol/L) group. Western blotting was used to detect the protein expression of IKBα, phosphorylated IKBα (p-IKBα), and p65 in the Con group, the LPS group, the AST (20 μmol/L) group, and the LPS+AST (20 μmol/L) group. After 10 μmol/L PDTC treatment, the mRNA and protein expressions of IL-6, IL-1β, and TNF-α were detected by RT-qPCR and ELISA.@*RESULTS@#Cell morphology and immunocytochemical staining showed that the cells were in line with the characteristics of hPDLCs. Treatment with AST could promote the proliferation of hPDLCs, which reached the peak at 20 μmol/L. The mRNA and protein expressions of IL-6, IL-1β, and TNF-α in the LPS group were higher than those in the Con group (all @*CONCLUSIONS@#AST promotes the proliferation of hPDLCs, which is related to suppression of LPS-induced the secretion of inflammatory factors via inhibiting the activation of NF-κB signaling pathway.

Cells, Cultured , Humans , Inflammation/chemically induced , Lipopolysaccharides , NF-kappa B , Periodontal Ligament , Tumor Necrosis Factor-alpha/genetics , Xanthophylls
Article in Chinese | WPRIM | ID: wpr-880073


In recent years, it is found that the classical IKKα and IKKβ pathway were closely relates with hematological tumors, except the classical pathogenesis, moreover the classical IKKβ pathway is deeply studied. The studies indicated that the IKKβis activated to phosphorylate the NF-κB through multiple cascades under the effect of extracellular IL-6, TNF-α and other stimulating factors. At the cellular level, the classical IKKβcan promote the tumor cell survival and proliferation, reduce the cell apoptosis, and promote the angiogenesis and cell transfer. Although the classical IKKα plays a role in regulating IKKβ activity, but its role in non-classical pathway is more prominent. This review briefly summarizes the latest advance of researches on the pathogenesis of hematological malignancies in term of IKKα and IKKβpathway, so as to provide the theoretic basis for deeply understanding and studying the pathogenesis of hematologic tumors. At present, blocking the classical IKKα and IKKβ pathway has become a new target for treatment of hematological tumors, moreover, some specific inhibitor for IKKα and IKKβpathway have been developed, for example, LY2409881, BMS 345541 and so on. Most of these drugs are in clinical trials and display some good anti-tumor effects.

Cell Survival , Hematologic Neoplasms , Humans , I-kappa B Kinase/metabolism , NF-kappa B/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha
Braz. arch. biol. technol ; 64: e21210256, 2021. tab, graf
Article in English | LILACS | ID: biblio-1339311


Abstract While the role of cytokines in celiac disease has been investigated in detail, cytokine release in the event of the exposure of healthy subjects to glutens has only recently been studied. This study was aimed at determining the effects of corn and wheat glutens, incorporated as protein sources into the diet, on serum interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels and the immunohistochemical distribution of CD3 and CD8 receptors in the small intestine in male rats. The study material comprised 24 twenty-day-old male Wistar albino rats, which were randomly assigned in equal numbers to three groups (2 rats/replicate and 4 replicates/group). The feed rations provided to all three groups contained high levels of proteins, which were soybean meal, corn gluten and wheat gluten in the control, corn and wheat groups, respectively. The in Control, Corn and Wheat groups serum IL-1 beta and TNF-alpha levels respectively 55.83 - 46.37; 81.65 - 61.95 and 81.65-61.31 was determined but these differences were statistically insignificant. Furthermore, immunohistochemical examination demonstrated a mathematical increase to have occurred in the distribution of the CD3 and CD8 receptors in the duodenum, jejunum and ileum samples of the corn and wheat groups. In result, based on the findings obtained in this study, we suggest that the long-term feeding of rats on high levels of gluten causes systemic adverse effects.

Animals , Rats , Cytokines/drug effects , Tumor Necrosis Factor-alpha/drug effects , Interleukin-1beta/drug effects , Glutens/pharmacology , Immunohistochemistry , Rats, Wistar
J. appl. oral sci ; 29: e20210160, 2021. tab, graf
Article in English | LILACS | ID: biblio-1340107


Abstract Objective This study aims to evaluate the effect of ellagic acid (EA) by measuring the levels of alveolar bone resorption and inflammatory and oxidative stress markers in the periodontal tissues and serum on the periodontal repair process related to experimental periodontitis in rats. Methodology Forty Wistar rats were divided into four study groups as follows: Group 1=healthy control (n=10); Group 2=EA control (15 mg/kg)(n=10); Group 3=periodontitis (n=10); Group 4=periodontitis+EA (15 mg/kg) (n=10). The periodontitis model was established by ligating bilateral mandibular first molars for 14 days. Then, rats were given normal saline or EA for another 14 days by gavage administration. Serum and gingiva myeloperoxidase (MPO) activity, 8-hydroxydeoxyguanosine(8-OHdG), and glutathione (GSH) levels were analyzed by ELISA. İmmunohistochemical analysis was used to detect Interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) immunoreactivities in the periodontal tissues. Alveolar bone loss (ABL) and attachment loss (AL) was evaluated by histomorphometry analysis. Results ABL and AL were statistically higher in group 3 than in groups 1, 2 and 4 and in group 4 than in groups 1 and 2 (p<0.05). MPO activities in gingival tissue and serum were significantly increased in group 3 compared to groups 1 and 2 (p<0.05). Significantly higher serum GSH levels, lower gingiva, and serum 8-OHdG levels, and MPO activity were observed in group 4 compared to group 3 (p<0.05). Rats with periodontitis (group 3) expressed significantly higher immunoreactivities of IL-6 and TNF-α and lower IL-10 immunoreactivity compared to those other groups (p<0.05). IL-6 and TNF-α immunoreactivities significantly decreased and IL-10 immunoreactivity increased in group 4 after the use of EA compared to group 3 (p<0.001). Conclusions Our findings showed that EA provides significant improvements on gingival oxidative stress and inflammatory markers and alveolar bone resorption in the repair process associated with experimental periodontitis. Therefore, EA may have a therapeutic potential on periodontitis.

Animals , Rats , Periodontitis/drug therapy , Alveolar Bone Loss , Tumor Necrosis Factor-alpha , Rats, Wistar , Ellagic Acid/pharmacology , Interleukin-1beta
Adv Rheumatol ; 61: 17, 2021. tab, graf
Article in English | LILACS | ID: biblio-1152736


Abstract Background: Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. Methods: Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. Results: Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = − 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. Conclusion: This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. Trial registration: This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426.(AU)

Humans , Spondylitis, Ankylosing/etiology , Homocysteine/analysis , Case-Control Studies , Methotrexate/therapeutic use , Tumor Necrosis Factor-alpha/therapeutic use
Rev. Assoc. Med. Bras. (1992) ; 66(12): 1638-1644, Dec. 2020. graf
Article in English | LILACS, SES-SP | ID: biblio-1143666


SUMMARY OBJECTIVE: To investigate the protective effect and mechanism of dexmedetomidine (Dex) on perioperative myocardial injury in patients with Stanford type-A aortic dissection (AD). METHODS: Eighty-six patients with Stanford type-A AD were randomly divided into Dex and control groups, with 43 cases in each group. During the surgery, the control group received the routine anesthesia, and the Dex group received Dex treatment based on routine anesthesia. The heart rate (HR) and mean arterial pressure (MAP) were recorded before Dex loading (t0), 10 min after Dex loading (t1), at the skin incision (t2), sternum sawing (t3), before cardiopulmonary bypass (t4), at the extubation (t5), and at end of surgery (t6). The blood indexes were determined before anesthesia induction (T0) and postoperatively after 12h (T1), 24h (T2), 48h (T3), and 72h (T4). RESULTS: At t2 and t3, the HR and MAP in the Dex group were lower than in the control group (P < 0.05). Compared with the control group, in the Dex group at T1, T2, and T3, the serum creatine kinase-MB, cardiac troponin-I, C-reactive protein, and tumor necrosis factor-α levels were decreased, and the interleukin-10 level, the serum total superoxide dismutase, and total anti-oxidant capability increased, while the myeloperoxidase and malondialdehyde levels decreased (all P < 0.05). CONCLUSIONS: Dex treatment may alleviate perioperative myocardial injury in patients with Stanford type-A AD by resisting inflammatory response and oxidative stress.

RESUMO OBJETIVO: Investigar o efeito protetor e o mecanismo da dexmedetomidina (Dex) na lesão perioperativa do miocárdio em doentes com dissecação aórtica Tipo A de Stanford (AD). MÉTODOS: Oitenta e seis pacientes com o Tipo A de Stanford foram aleatoriamente divididos em Dex e grupos de controle, 43 casos em cada grupo. Durante a cirurgia, o grupo de controle recebeu a anestesia de rotina, e o grupo Dex recebeu tratamento Dex baseado na anestesia de rotina. A frequência cardíaca (AR) e a pressão arterial média (MAP) foram registradas no momento anterior ao Dex carregar (t0), 10 minutos após o Dex carregar (t1), incisão cutânea (t2), serragem de esterno (t3), antes do bypass cardiopulmonar (t4), extubação (t5) e fim da cirurgia (t6). Os índices de sangue foram determinados no momento antes da indução da anestesia (T0) e no pós-operatório 12 horas (T1), 24 horas (T2), 48 horas (T3) e 72 horas (T4). RESULTADOS: Em T2 e t3, o RH e o MAP do grupo Dex foram inferiores ao grupo de controle (p<0,05). Em comparação com o grupo de controle, no grupo Dex em T1, T2 e T3, os níveis séricos de creatina quinase-MB, troponina-I, proteína C-reativa e necrose do fator-α do tumor diminuíram, o nível interleucina-10 aumentou, o desalinhamento total do superóxido sérico e a capacidade antioxidante total aumentaram e os níveis de mielopeperóxido e malondialdeído diminuíram (todos p<0,05). CONCLUSÃO: O tratamento com Dex pode aliviar a lesão do miocárdio perioperativo em doentes com o Tipo A de Stanford por resistência à resposta inflamatória e ao estresse oxidativo.

Humans , Dexmedetomidine , Aneurysm, Dissecting/surgery , Aneurysm, Dissecting/prevention & control , Tumor Necrosis Factor-alpha , Peroxidase , Heart Rate
J. coloproctol. (Rio J., Impr.) ; 40(4): 421-424, Oct.-Dec. 2020.
Article in English | LILACS | ID: biblio-1143175


ABSTRACT Perianal fistulizing Crohn's disease (PFCD) is one of the most complex challenges in the colorectal surgery nowadays, because, even with combined clinical and surgical treatment, the rate of healing of the fistulas is approximately 50%. In this context, the monitoring of serum levels of anti-Tumor Necrosis Factor (anti-TNF) drugs appears as a crucial tool for the optimization of treatment, since there is a probable correlation between higher serum levels of infliximab and adalimumab with better outcomes of the disease, higher healing rates and lower recurrence rates. This review describes evidence on the use of serum anti-TNF levels and their relationship to clinical and radiological efficacy.

RESUMO A Doença de Crohn Perianal Fistulizante (DCPF) configura-se como um dos desafios mais complexos da cirurgia colorretal atualmente, isso porque, mesmo com tratamento clínico e cirúrgico combinados, a taxa de cicatrização das fistulas é de aproximadamente 50%. Nesse contexto, a monitorização de níveis séricos de drogas anti-Fator de Necrose Tumoral (anti-TNF) surge como ferramenta crucial para a otimização do tratamento, uma vez há provável correlação entre maiores níveis séricos de infliximabe e adalimumabe com melhores desfechos da doença, maiores taxas de cicatrização e menores índices de recorrência. Nesta revisão são descritas evidências sobre o uso dos níveis séricos de anti-TNF e sua relação com a eficácia clínica e radiológica.

Humans , Crohn Disease/pathology , Tumor Necrosis Factor-alpha/therapeutic use , Fistula/complications
Arq. gastroenterol ; 57(3): 323-332, July-Sept. 2020. tab, graf
Article in English | LILACS | ID: biblio-1131674


ABSTRACT BACKGROUND: Inflammatory bowel diseases (IBD), both Crohn's disease and ulcerative colitis, are chronic immune-mediated diseases that present a relapsing and remitting course and requires long-term treatment. Anti-tumor necrosis factor (anti-TNF) therapy has changed the management of the disease by reducing the need for hospitalizations, surgeries and improving patient´s quality of life. OBJECTIVE: The aim of this review is to discuss the role of anti-TNF agents in IBD, highlighting the situations where its use as first-line therapy would be appropriate. METHODS: Narrative review summarizing the best available evidence on the topic based on searches in databases such as MedLine and PubMed up to April 2020 using the following keywords: "inflammatory bowel disease'', "anti-TNF agents" and ''biologic therapy''. CONCLUSION: Biological therapy remains the cornerstone in the treatment of IBD. In the absence of head-to-head comparisons, the choice of the biological agent may be challenging and should take into account several variables. Anti-TNF agents should be considered as first line therapy in specific scenarios such as acute severe ulcerative colitis, fistulizing Crohn's disease and extra-intestinal manifestations of IBD, given the strong body of evidence supporting its efficacy and safety in these situations.

RESUMO CONTEXTO: As doenças inflamatórias intestinais (DII), tanto a doença de Crohn (DC) como a retocolite ulcerativa (RCU), são doenças crônicas imunomediadas que se apresentam com períodos de surto e remissão e requerem terapia a longo prazo. A terapia com anti-fator de necrose tumoral (anti-TNF) tem mudado o manejo da doença reduzindo a necessidade de hospitalizações, cirurgias e melhorando a qualidade de vida dos pacientes. OBJETIVO: O objetivo do presente trabalho é apresentar uma revisão sobre a importância dos agentes anti-TNF no contexto da DII, levando em consideração situações em que essas drogas são usadas como terapia de primeira linha. MÉTODOS: Revisão narrativa baseada nas melhores evidências disponíveis na literatura através de buscas feitas nas bases de dados MedLine e PubMed até abril de 2020, utilizando as seguintes palavras chaves: "doença inflamatória intestinal'', "agentes anti-TNF" e "terapia biológica". CONCLUSÃO: A terapia biológica permanece sendo fundamental no tratamento da DII. Na ausência de estudos "head-to-head'' comparando os biológicos entre si, a escolha do agente biológico pode ser um desafio na prática clínica e múltiplas variáveis devem ser levadas em consideração. Os agentes anti-TNF devem ser considerados terapia de primeira linha em situações específicas como na colite ulcerativa aguda grave, na doença de Crohn fistulizante e nas manifestações extra-intestinais da doença inflamatória intestinal, uma vez que há evidências científicas robustas que sustentam a sua eficácia e segurança nessas situações.

Humans , Inflammatory Bowel Diseases/drug therapy , Quality of Life , Biological Factors , Tumor Necrosis Factor-alpha
Arq. bras. med. vet. zootec. (Online) ; 72(4): 1329-1338, July-Aug. 2020. tab, graf
Article in English | ID: biblio-1131492


The aim of this work was to measure HMGB1, TNF-alpha, and IL-8 in bronchoalveolar lavage (BAL), serum and TLR2 and TLR4mRNA expression in lung tissue of rabbits with two grades of acute lung injury (ALI). The animals were randomly assigned to groups with severe (S) and mild/moderate (MM) ALI, induced with warm saline, and a control group. HMGB1, TNF-alpha, IL-8, TLR2mRNA and TLR4mRNA were measured after ALI induction. The results showed increased levels of IL-8, TNF-alpha, HMGB1 and TLR4mRNA in the ALI groups. HMGB1, IL-8 and TNF-alpha concentrations in BAL were higher in S compared MM. Increased TLR4mRNA was observed in S and MM versus control. The results suggest an early participation of HMGB1 in ALI together with IL-8 and TNF-alpha and association with severity. TLR4 has early expression and role in ALI pathophysiology but is not associated with severity.(AU)

O objetivo deste trabalho é determinar os níveis de HMGB1, TNF-alfa e IL-8 no lavado broncoalveolar (BAL), bem como quantificar a expressão sérica de TLR2 e TLR4 mRNA em tecido pulmonar de coelhos com dois graus de lesão pulmonar aguda (LPA). Os animais foram distribuídos aleatoriamente em grupos com LPA grave (S) e leve / moderada (MM), induzidas com solução salina morna, e um grupo controle. HMGB1, TNF-alfa, IL-8, TLR2mRNA e TLR4mRNA foram medidos após a indução de LPA e quatro horas de ventilação mecânica. Os resultados mostraram níveis aumentados de IL-8, TNF-alfa, HMGB1 e TLR4mRNA nos grupos com LPA. As concentrações de HMGB1, IL-8 e TNF-alfa no LBA foram maiores no S comparado ao MM. Aumento de TLR4mRNA foi observado em S e MM versus controle. Os resultados sugerem uma participação precoce da HMGB1 na LPA em conjunto com IL-8 e TNF-alfa e associação com a gravidade da LPA. O TLR4 foi expresso na ALI e possivelmente possui papel precoce na fisiopatologia da LPA, mas sem associação com a gravidade.(AU)

Animals , Rabbits , Cytokines , HMGB1 Protein , Acute Lung Injury , RNA, Messenger , Interleukin-8 , Tumor Necrosis Factor-alpha , Toll-Like Receptor 2 , Toll-Like Receptor 4
Braz. dent. j ; 31(3): 290-297, May-June 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1132302


Abstract Chloride intracellular channel-4 (CLIC4) is regulated by p53 and tumor necrosis factor-α (TNF-α), it is linked to the increase of transforming growth factor-β (TGF-β), and myofibroblastic differentiation in skin carcinogenesis. This study analyzed the immunoexpression of CLIC4, p53, TGF-β, TNF-α, and α-SMA in 50 actinic cheilitis (AC) and 50 lower lip squamous cell carcinoma (LLSCC). AC and LLSCC immunoexpression were categorized as score 1 (<5% positive cells), 2 (5-50%) or 3 (>50%). For CLIC4, nuclear and cytoplasmic immunostaining of epithelial cells was considered individually. For morphologic analysis, the World Health Organization criteria were used to epithelial dysplasia grade of ACs, and Bryne grading of malignancy system was applied for LLSCC. Higher nuclear CLIC4 (CLIC4n) and TGF-β were observed in ACs with low-risk of transformation, while cytoplasmic CLIC4 (CLIC4c), p53 and TNF-α were higher in the high-risk cases (p<0.05). In LLSCCs, CLIC4c was higher in cases with lymph node metastasis, advanced clinical stages, and histological high-grade malignancy. p53 expression was higher in high-grade LLSCCs, whereas TGF-β decreased as the clinical stage and morphological grade progressed (p<0.05). ACs showed an increased expression of CLIC4n and TGF-β, while CLIC4c and α-SMA were higher in LLSCCs (p<0.0001). Both lesions showed negative correlation between CLIC4n and CLIC4c, while in LLSCCs, negative correlation was also verified between CLIC4c and p53, as well as CLIC4c and TGF-β (p<0.05). Change of CLIC4 from the nucleus to cytoplasm and alterations in p53, TGF-β, TNF-α, and α-SMA expression are involved in lip carcinogenesis.

Resumo O canal intracelular de cloreto 4 (CLIC4) é regulado pela p53 e fator de necrose tumoral α (TNF-α) e está relacionado ao aumento do fator de crescimento transformador β (TGF-β) e na diferenciação miofibroblástica na carcinogênese cutânea. Este estudo analisou a imunoexpressão de CLIC4, p53, TGF-β, TNF-α e α-SMA em 50 queilites actínicas (QA) e 50 carcinomas de células escamosas de lábio inferior (CCELI). A imunoexpressão da QA e CCELI foram categorizadas em escore 1 (<5% de células positivas), 2 (5-50%) ou 3 (>50%). Para CLIC4, a imunomarcação nuclear e citoplasmática das células epiteliais foi considerada separadamente. Para análise morfológica, foram utilizados os critérios da Organização Mundial da Saúde para a gradação das displasias epiteliais nas QAs, e o sistema de gradação de malignidade de Bryne foi utilizado para os casos de CCELIs. Alta imunoexpressão de CLIC4 nuclear (CLIC4n) e TGF-β foi observada em QA de baixo risco de transformação, enquanto CLIC4 citoplasmática (CLIC4c), p53 e TNF-α foram elevadas nos casos de alto risco (p<0.05). No CCELI, a imunoexpressão de CLIC4c foi maior em caos com metástase linfonodal, estágio clínico avançado e alto grau histológico de malignidade. A expressão de p53 foi elevada em CCELI de alto grau, enquanto o TGF-β diminuiu à medida que o estádio clínico e o grau morfológico progrediram (p<0.05). QAs exibiram uma elevada expressão de CLIC4n e TGF-β, enquanto o CLIC4c e α-SMA foram elevados em CCELIs (p<0.0001). Ambas as lesões mostraram correlação negativa entre CLIC4n e CLIC4c, enquanto nos CCELIs, também se verificou correlação negativa entre CLIC4c e p53, assim como entre CLIC4c e TGF-β (p<0.05). Alteração do CLIC4 do núcleo para o citoplasma e alterações na expressão de p53, TGF-β, TNF-α, e α-SMA estão envolvidas na carcinogênese labial.

Humans , Lip Neoplasms , Transforming Growth Factor beta , Tumor Suppressor Protein p53 , Tumor Necrosis Factor-alpha , Chloride Channels , Myofibroblasts , Carcinogenesis , Lip
Diagn. tratamento ; 25(2): 01-04, abr.-jun. 2020.
Article in Portuguese | LILACS | ID: biblio-1116011


Contexto: O infliximabe é um anticorpo monoclonal quimérico que atua neutralizando a atividade biológica do fator de necrose tumoral alfa e impedindo a ligação da molécula aos receptores da célula-alvo. A melhora da psoríase ocorre logo nas primeiras semanas do seu uso, e está indicado, especialmente, em quadros graves, tanto cutâneos quanto articulares, nos quais necessitam pronta ação terapêutica. Descrição do caso: Relata-se caso de uma paciente com psoríase grave refratária a terapias sistêmicas prévias, incluindo metotrexate, ustequinumabe, secuquinumabe, acitretina e ciclosporina, com melhora de 70% em relação a avaliação inicial no índice de gravidade da psoríase por área, após início de fase de indução com infliximabe. Discussão: A paciente apresentou resposta satisfatória à terapia combinada de infliximabe com ciclosporina e acitretina, sem qualquer manifestação de eventos adversos, mas com melhoria das lesões e dos escores de avaliação. Poucos relatos de caso e estudos randomizados estão presentes na literatura sobre a associação de ciclosporina e imunobiológicos, devido ao risco de imunossupressão grave, porém no caso relatado não houve aumento desse risco. Entretanto, reconhecemos que é impossível avaliar adequadamente a efetividade e a segurança de qualquer tratamento com anticorpo monoclonal para doenças crônicas com apenas 14 dias de seguimento. Conclusão: O antifator de necrose tumoral alfa associado a ciclosporina mostrou ser uma combinação efetiva durante a fase de indução e e de grande valia neste caso, em que a paciente apresentava psoríase refratária a outras terapêuticas e necessidade de rápida resposta clínica.

Humans , Female , Middle Aged , Psoriasis , Tumor Necrosis Factor-alpha , Cyclosporine , Combined Modality Therapy , Infliximab
Int. j. morphol ; 38(3): 558-564, June 2020. tab, graf
Article in English | LILACS | ID: biblio-1098287


Chronic hepatotoxicity is a debilitating and frequently life-threatening disease resulting in progressive liver failure. The toxic chemical, thioacetamide (TAA) is used to evaluate hepatoprotective agents, and the polyphenolic compound, resveratrol was proposed as a novel treatment for diseases with hyperactivation of the mammalian target of rapamycin (mTOR) cell signaling pathway. This analysis sought to investigate the potential protective effect of resveratrol against liver injury induced by TAA via the inhibition of hepatic mTOR. Model group rats received several injections of TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed at week 10 and the protective group was pretreated with resveratrol (20 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for biomarkers of inflammation and assessed the levels of mTOR protein in all animal groups. In addition, blood samples were assayed for biomarkers of liver injury enzyme. TAA substantially damaged the hepatic tissue of the model group such as infiltration of inflammatory cells, vacuolated cytoplasm, dark pyknotic nuclei, and dilated congested blood vessel that were effectively protected by resveratrol. Resveratrol also significantly (p<0.05) inhibited TAA-induced mTOR, high sensitivity c-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in harvested liver homogenates and blood samples. Thus, we conclude that resveratrol effectively protects against TAA-induced hepatotoxicity in rats, possibly due to the inhibition of mTOR and inflammation.

La hepatotoxicidad crónica es una enfermedad debilitante y potencialmente mortal que produce insuficiencia hepática progresiva. La toxicidad del químico de la tioacetamida (TAA) se utiliza para evaluar los agentes hepatoprotectores y el compuesto polifenólico, resveratrol, se propuso como un nuevo tratamiento para enfermedades con hiperactivación de la vía de señalización celular mTOR (mammalian Target of Rapamycin). Aquí buscamos investigar el posible efecto protector del resveratrol contra la lesión hepática inducida por TAA a través de la inhibición de la vía de señalización mTOR en hepatocitos. Las ratas del grupo modelo recibieron varias inyecciones de TAA (200 mg / kg; dos veces por semana durante 8 semanas) antes de ser sacrificadas en la semana 10 y el grupo protector se trató previamente con resveratrol (20 mg / kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuó recibiendo ambos agentes hasta el final del experimento. Se examinaron los tejidos hepáticos recolectados usando microscopía óptica y se analizaron los homogeneizados hepáticos para detectar biomarcadores de inflamación y se evaluaron los niveles de proteína mTOR en todos los grupos de animales. Además, se analizaron muestras de sangre para detectar biomarcadores de la enzima de lesión hepática. TAA dañó sustancialmente el tejido hepático del grupo modelo, con infiltración de células inflamatorias, citoplasma vacuolado, núcleos picnóticos oscuros y vasos sanguíneos congestionados dilatados que estaban efectivamente protegidos por el resveratrol. El resveratrol también inhibió significativamente (p <0.05) mTOR, proteína C-reactiva (hs-CRP), factor de necrosis tumoral alfa (TNF-α), interleucina-6 (IL-6), alanina aminotransferasa (ALT ) y aspartato aminotransferasa (AST) en las muestras de sangre y de hígados recolectados. En conclusión, el resveratrol protege eficazmente contra la hepatotoxicidad inducida por TAA en ratas, posiblemente debido a la inhibición de mTOR y de la inflamación.

Animals , Male , Mice , Thioacetamide/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , TOR Serine-Threonine Kinases/antagonists & inhibitors , Resveratrol/administration & dosage , Aspartate Aminotransferases/analysis , C-Reactive Protein/analysis , Tumor Necrosis Factor-alpha/analysis , Alanine Transaminase/analysis , Disease Models, Animal
J. oral res. (Impresa) ; 9(2): 86-92, abr. 30, 2020. ilus, tab
Article in English | LILACS | ID: biblio-1151843


Introduction: Lichen planus is one of the most common oral mucosal lesions. Transforming growth factor-ß (TGF- ß) has a marked effect on epithelial­mesenchymal transition and immune cells function. Vascular Endothelial Growth Factor (VEGF) is a key regulator of vasculogenesis and angiogenesis. Tumor necrosis factor-α (TNF-α) mediates T-lymphocyte homing and apoptosis of epithelial cells. Objetive: The present study was conducted in order to compare the expression of serum and salivary TGF- ß, VEGF, TNF-α between OLP patients and control individuals to investigate if saliva can be used as an alternative to serum for diagnostic purposes and for monitoring disease. Materials and Methods: 23 OLP patients and 23 control individuals were included to evaluate serum and salivary TGF-ß, VEGF, TNF-α using ELISA kits. Five milliliters of venous blood was collected and unstimulated saliva was collected by the spitting method. Results: Serum and salivary levels of TGF- ß, VEGF, TNF-α are higher in OLP patients compared to normal controls. Mean difference is higher in saliva than serum. Moreover, there was a significant difference in serum and salivary VEGF and TNF-α between symptomatic and asymptomatic groups. Conclusions: Saliva can be a used as a substitute for serum to evaluate levels of the assessed biomarkers.

Introducción: El liquen plano oral es una de las lesiones de la mucosa oral más comunes. El factor de crecimiento transformante ß (TGF-ß) tiene un efecto marcado sobre la transición epitelial-mesenquimal y la función de las células inmunes. El factor de crecimiento endotelial vascular (VEGF) es un regulador clave de la vasculogénesis y la angiogénesis. El factor de necrosis tumoral α (TNF-α) media la localización de los linfocitos T y la apoptosis de las células epiteliales. Objetivo: El presente estudio se realizó con el fin de comparar la expresión en suero y saliva de TGF-ß, VEGF, TNF-α entre pacientes con OLP y personas de control para investigar si la saliva se puede utilizar como alternativa al suero para fines de diagnóstico y monitoreo de la enfermedad. Material y Métodos: Se incluyeron 23 pacientes con OLP y 23 individuos control para evaluar los niéveles en suero y en saliva de TGF- ß, VEGF, TNF-α utilizando kits ELISA. Se recogieron cinco mililitros de sangre venosa y se recogió saliva no estimulada por el método de escupir. Resultado: Los niveles séricos y salivales de TGF-ß, VEGF, TNF-α son más altos en pacientes con OLP en comparación con los controles normales. La diferencia media es mayor en saliva que en suero. Además, hubo una diferencia significativa de VEGF y TNF-α en suero y saliva entre los grupos sintomáticos y asintomáticos. Conclusion: La saliva puede usarse como un sustituto del suero para evaluar los niveles de los biomarcadores estudiados

Humans , Male , Female , Saliva/metabolism , Transforming Growth Factor beta , Tumor Necrosis Factor-alpha , Lichen Planus, Oral/diagnosis , Serum/metabolism , Vascular Endothelial Growth Factor A , Egypt , Mouth Mucosa , Necrosis