Identification of IL-18 and Soluble Cell Adhesion Molecules in the Gingival Crevicular Fluid as Novel Biomarkers of Psoriasis.

Psoriasis is a chronic immunoinflammatory skin disease. Although its diagnosis is clinical, differences in the appearance and severity of lesions pose a challenge for clinicians worldwide. The use of accessible biomarkers for psoriasis could aid in the early diagnosis and treatment of the disease. To date, evidence on the analysis of gingival crevicular fluid (GCF) molecules as novel, accessible, and reliable biomarkers for psoriasis is limited. This cross-sectional study compared the GCF levels of IL-18, soluble (s)ICAM-1, and sE-selectin in psoriatic patients (n = 42) and healthy controls (n = 39). Individuals with psoriasis not undergoing treatment and healthy individuals were included independent of periodontal status. GCF samples were collected, and a multiplex bead immunoassay was performed to quantify the levels of the target molecules. Psoriatic patients presented higher concentrations of IL-18 and lower concentrations of sE-selectin compared to controls (p < 0.05). No differences were found in the levels of sICAM-1 between the two groups (p > 0.05). Psoriasis was associated with IL-18 and E-selectin levels regardless of periodontal status, age, and smoking habit (p < 0.05). The areas under the receiver operating characteristic curve (ROC) for IL-18 and sE-selectin were 0.77 and 0.68, respectively. In conclusion, IL-18 and sE-selectin levels in the GCF could be promising biomarker for psoriasis.

Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis

Abstract: Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

Adhesion molecules before and after propylthiouracil in patients with subclinical hyperthyroidism

SUMMARY OBJECTIVE This study aimed to investigate the effect of propylthiouracil treatment on adhesion molecules in patients with subclinical hyperthyroidism. METHODS In this study, a total of 168 patients diagnosed with subclinical hyperthyroidism were treated with propylthiouracil for one year. The levels of adhesion molecules, consisting of sICAM-1, sVCAM-1, and sE-Selectin, before and after the treatment were measured and compared. These results were compared with the levels of 148 healthy controls who received a placebo. RESULTS sICAM-1 levels were significantly higher in subclinical hyperthyroidism patients than in healthy controls (*pa=0.000). sICAM-1 levels were significantly decreased after the treatment (**pb=0.000). Despite this decrease in patients with subclinical hyperthyroidism, it did not decrease to the level of the control group. sVCAM-1 did not change before and after propylthiouracil treatment. The level of sE-selectin was similar to that of the pretreatment control group, but it did not have statistical significance, although it increased after the treatment (**pb=0.004). CONCLUSION The sICAM level was significantly higher than the pretreatment values and decreased after the propylthiouracil treatment. However, further studies are needed to reduce the risk of atherosclerosis and cancer in patients with subclinical hyperthyroidism.

RESUMO ANTECEDENTES O objetivo deste estudo foi investigar o efeito do tratamento com propiltiouracil nas moléculas de adesão em pacientes com hipertireoidismo subclínico. MÉTODOS Neste estudo, 168 pacientes diagnosticados com hipertireoidismo subclínico foram tratados com propiltiouracil por um ano. Os níveis de moléculas de adesão, especificamente sICAM-1, sVCAM-1 e sE-Selectina, antes e após o tratamento foram medidos e comparados. Esses resultados foram comparados com os níveis de 148 indivíduos saudáveis no grupo de controle que receberam um placebo. RESULTADOS Os níveis de sICAM-1 foram significativamente maiores em pacientes com hipertireoidismo subclínico do que nos controles saudáveis (*pa=0,000). Os níveis de sICAM-1 diminuíram significativamente após o tratamento (**pb=0,000). Apesar dessa diminuição em pacientes com hipertireoidismo subclínico, ela não diminuiu para o nível do grupo controle. O sVCAM-1 não se alterou antes e após o tratamento com propiltiouracil. O nível de sE-Selectina foi semelhante ao do grupo de controle pré-tratamento, mas não apresentou significância estatística, embora tenha aumentado após o tratamento (** pb = 0,004). CONCLUSÃO O nível de sICAM foi significativamente superior aos valores pré-tratamento e diminuiu após o tratamento com propilciliouracil. No entanto, mais estudos são necessários para reduzir o risco de aterosclerose e câncer em pacientes com hipertireoidismo subclínico.

Effect of intercellular adhesion molecule 1 deficiency on the development of apical periodontitis.

AIM: To evaluate the specific role of ICAM-1 in host responses against endodontic infection. METHODS: Apical periodontitis was experimentally induced in the mandibular first molars of ICAM-1 knockout and wild-type (WT) mice by pulp exposure to the oral environment. At 7, 21 and 42 days following pulp infection, the animals were euthanized and the jaws were prepared for analysis under conventional and fluorescence microscopy (histopathologic and morphometric analysis), immunohistochemistry (polymorphonuclear leucocytes), enzyme histochemistry (osteoclasts and cementoclasts) and RT-PCR (IL-1 α, TNF-α, INF-γ, IL-10, RANK, RANKL and OPG). A generalized linear model with GLIMMIX procedure with Satterthwaite approximation method of degrees of freedom, Tukey-Kramer, pseudo-ranking nonparametric, Bonferroni-Holm multiple testing adjustment, analysis of variance (ANOVA) and the Tukey's multiple comparisons tests were used to evaluate the statistical differences between the groups using SAS 9.4 and the GraphPad Prism 5.0 software (α = 0.05). RESULTS: Compared to WT mice, ICAM-1 knockout mice had significantly greater bone resorption (P < 0.05), reduced recruitment of neutrophils to periapical inflammatory tissues (P < 0.05) and an increased number of fibroblasts (P < 0.05) at all experimental periods. The osteoclast number was significantly higher in ICAM-1 KO than that of WT animals at all times (P < 0.05), while there was no significant difference between the groups regarding cementoclasts. At day 21, the level of IL-1α, RANK, RANKL and IL-10 had increased significantly in tissues from ICAM-1 KO versus WT mice (P < 0.05), while no significant difference was observed in TNF-α and OPG levels (P > 0.05). Tissue levels of INF-γ were significantly lower in ICAM-1 KO than those in WT mice (P < 0.05). CONCLUSION: ICAM-1 deficiency impaired the host response against endodontic infection, resulting in increased tissue destruction.

Suppresses of Astragalus Polysaccharide on E. coli-Induced Injured Intestinal Microvascular through TLR4-NF-B Signal Pathways in Chickens

To investigate the hypothesis that APS can attenuate E. coli-induced microvascular dysfunction in chicken intestine, 60 0-day old male chickens were divided into three groups with 5 replications of 4 chicks. Chicken in the APS group were treated with 15 mg APS daily while the others were given 0 mg APS for 6 days. Then all 7-day old chicken were injected intraperitoneally by E. coli, except for the chicken in the control group. After 4 h, all chickens intestinal samples were collected to detect gene expressions involved in inflammatory factors and adhesion molecules. Results showed that APS attenuated the signs of edema and hemorrhage in 7-day old chicken intestinal mucosa which were induced by E. coli injection. Consistently, APS significantly reduced the increasing mRNA levels of inflammatory factors such as Tumor necrosis factor-a (TNF-a), interleukin (IL) -1 and inducible nitric oxide synthase (iNOS) (p 0.05), the same results were observed in vascular adhesion molecules such as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, we observed that APS supplementation in water suppressed significantly (p 0.05) the decline of reparative factors such as epithelial growth factor (EGF) and basic fibroblast growth factor (bFGF) in E. coli injected group. Furthermore, supplementation with APS substantially blocked (p 0.05) the increase in Toll-like receptor-4 (TLR4) and Nuclear factor (NF)-B mRNA abundance (p=0.087) induced by E. coli infection. This study indicated that microvascular injured chicken intestine induced by E. coli would be attenuated with feeding APS, and the mechanism of repairing were probably mediated through TLR4-NF-B signal pathways.

Suppresses of Astragalus Polysaccharide on E. coli-Induced Injured Intestinal Microvascular through TLR4-NF-B Signal Pathways in Chickens

To investigate the hypothesis that APS can attenuate E. coli-induced microvascular dysfunction in chicken intestine, 60 0-day old male chickens were divided into three groups with 5 replications of 4 chicks. Chicken in the APS group were treated with 15 mg APS daily while the others were given 0 mg APS for 6 days. Then all 7-day old chicken were injected intraperitoneally by E. coli, except for the chicken in the control group. After 4 h, all chickens intestinal samples were collected to detect gene expressions involved in inflammatory factors and adhesion molecules. Results showed that APS attenuated the signs of edema and hemorrhage in 7-day old chicken intestinal mucosa which were induced by E. coli injection. Consistently, APS significantly reduced the increasing mRNA levels of inflammatory factors such as Tumor necrosis factor-a (TNF-a), interleukin (IL) -1 and inducible nitric oxide synthase (iNOS) (p 0.05), the same results were observed in vascular adhesion molecules such as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, we observed that APS supplementation in water suppressed significantly (p 0.05) the decline of reparative factors such as epithelial growth factor (EGF) and basic fibroblast growth factor (bFGF) in E. coli injected group. Furthermore, supplementation with APS substantially blocked (p 0.05) the increase in Toll-like receptor-4 (TLR4) and Nuclear factor (NF)-B mRNA abundance (p=0.087) induced by E. coli infection. This study indicated that microvascular injured chicken intestine induced by E. coli would be attenuated with feeding APS, and the mechanism of repairing were probably mediated through TLR4-NF-B signal pathways.(AU)

Immune-Mediated Inflammation Promotes Subclinical Atherosclerosis in Recent-Onset Psoriatic Arthritis Patients without Conventional Cardiovascular Risk Factors.

Studies on the inflammatory burden in recent-onset psoriatic arthritis (PsA) patients without conventional cardiovascular risk factors (CVRFs) are not available. This preliminary study focuses on cardiovascular risk in cutaneous psoriasis (CPs) and recent-onset PsA patients. Blood biochemistry (glucose, cholesterol, uric acid, lipid profile and apolipoprotein B) was analyzed using standard kits. Proatherogenic inflammation markers, C-reactive protein (CRP) and interleukin-6 (IL-6), and endothelial activators monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1 (sICAM-1), were determined by enzyme-linked immunosorbent assay. Ultrasound images allowed measuring carotid intima-media thickness (cIMT). Our study first shows an increase in cIMT, and in serum levels of sICAM-1 and CRP in recent-onset PsA patients not presenting conventional CVRFs over the non-medicated time-period, from disease diagnosis to the beginning of pharmacological treatment, compared with healthy subjects. The outcome highlights the importance of monitoring serum level of sICAM1, CRP, and cIMT, and the value of primary prevention in psoriatic patients even with no history of cardiovascular events.

Polymorphisms of ICAM-1 and IL-6 genes related to endometriosis in a sample of Brazilian women.

PURPOSE: This study investigated the possibility of K469E (rs5498) and G241R (rs1799969) polymorphisms, in ICAM-1 gene, and G634C (rs1800796), in IL-6 gene, being associated with the occurrence of endometriosis in a sample of Brazilian women. METHODS: We genotyped 200 women (100 in control group and 100 in endometriosis group) by PCR-RFLP technique for G634C, K469E, and G241R polymorphisms. RESULTS: No significant difference was observed in genotypic frequency between control and endometriosis groups for G634C and K469E polymorphisms (p = 0.61 and p = 0.22, respectively). In addition, no significant difference between stages I-II and III-IV of the disease was found for both SNPs (p = 0.63 and p = 0.24, respectively). All individuals were wild homozygotes for G241R polymorphism. CONCLUSION: This study suggests that polymorphisms K469E, G241R, and G634C are not associated with increased susceptibility to endometriosis in Brazilian women.

Blood cells and endothelial barrier function.

The barrier properties of endothelial cells are critical for the maintenance of water and protein balance between the intravascular and extravascular compartments. An impairment of endothelial barrier function has been implicated in the genesis and/or progression of a variety of pathological conditions, including pulmonary edema, ischemic stroke, neurodegenerative disorders, angioedema, sepsis and cancer. The altered barrier function in these conditions is often linked to the release of soluble mediators from resident cells (e.g., mast cells, macrophages) and/or recruited blood cells. The interaction of the mediators with receptors expressed on the surface of endothelial cells diminishes barrier function either by altering the expression of adhesive proteins in the inter-endothelial junctions, by altering the organization of the cytoskeleton, or both. Reactive oxygen species (ROS), proteolytic enzymes (e.g., matrix metalloproteinase, elastase), oncostatin M, and VEGF are part of a long list of mediators that have been implicated in endothelial barrier failure. In this review, we address the role of blood borne cells, including, neutrophils, lymphocytes, monocytes, and platelets, in the regulation of endothelial barrier function in health and disease. Attention is also devoted to new targets for therapeutic intervention in disease states with morbidity and mortality related to endothelial barrier dysfunction.

Effects of Human Umbilical Cord Mesenchymal Stem Cells on Renal Ischaemia-reperfusion Injury in Rats

Objective This study aims to observe the function of umbilical cord-mesenchymal stem cells (UC-MSCs) labelled with enhanced green fluorescent protein (eGFP) in the repair of renal ischaemia-reperfusion (I/R) injury, to determine the effects on inflammatory cascade in an established rat model and to explore possible pathogenesis. Materials and Methods Sixty rats were randomly divided into three groups: the sham-operated, I/R and UC-MSC treatment groups. All rats underwent right nephrectomy. Ischaemia was induced in the left kidney by occlusion of the renal artery and vein for 1hour, followed by reperfusion for 24 hours or 48 hours. Kidney samples were collected to observe morphological changes. Immunohistochemistry was performed to assess the expression of intercellular adhesion molecule 1 (ICAM-1) in the renal tissue sample, as well as the number of infiltrating polymorphonuclear neutrophils (PMNLs) and UC-MSCs with positive eGFP. Results Renal histopathological damages and the expression of ICAM-1 and PMNL increased significantly in the I/R group compared with those in the sham-operated group, whereas the damages were less conspicuous in the UC-MSC treatment group. Conclusions Renal ICAM-1, which mediated PMNL infiltration and contributed to renal damage, was significantly up-regulated in the I/R group. UC-MSCs were identified to inhibit these pathological processes and protect the kidney from I/R injury. .

Expression, production, and renaturation of a functional single-chain variable antibody fragment (scFv) against human ICAM-1

Intercellular adhesion molecule-1 (ICAM-1) is an important factor in the progression of inflammatory responses in vivo. To develop a new anti-inflammatory drug to block the biological activity of ICAM-1, we produced a monoclonal antibody (Ka=4.19×10−8 M) against human ICAM-1. The anti-ICAM-1 single-chain variable antibody fragment (scFv) was expressed at a high level as inclusion bodies in Escherichia coli. We refolded the scFv (Ka=2.35×10−7 M) by ion-exchange chromatography, dialysis, and dilution. The results showed that column chromatography refolding by high-performance Q Sepharose had remarkable advantages over conventional dilution and dialysis methods. Furthermore, the anti-ICAM-1 scFv yield of about 60 mg/L was higher with this method. The purity of the final product was greater than 90%, as shown by denaturing gel electrophoresis. Enzyme-linked immunosorbent assay, cell culture, and animal experiments were used to assess the immunological properties and biological activities of the renatured scFv.

Exogenous normal lymph alleviates lipopolysaccharide-induced acute lung injury through lessening the adhesion molecules

PURPOSE: To evaluate the role of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. METHODS: ALI was induced by the jugular vein injection of LPS (iv, 15 mg/kg) in rats of the LPS and LPS+ENL groups within 15 min, then, ENL without cell components (5 ml/kg) was infused at the speed of 0.5 ml per minute in the LPS+ENL group, the same amount of saline was administered in the LPS group. The rats in the sham group received the same surgical procedure and saline. The histomorphology and the levels of P-selectin, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) in pulmonary tissue were assessed. RESULTS: LPS induced pulmonary injury as well as increased the wet/dry weight ratio (W/D) and the levels of P-selectin, ICAM-1, and MPO in pulmonary tissues. These deleterious effects of LPS were significantly ameliorated by ENL treatment. CONCLUSION: Exogenous normal lymph could markedly alleviate the acute lung injury induced by lipopolysaccharide, and its effects might be related to lessening the adhesion molecules. .

Exogenous normal lymph alleviates lipopolysaccharide-induced acute lung injury through lessening the adhesion molecules

To evaluate the role of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. ALI was induced by the jugular vein injection of LPS (iv, 15 mg/kg) in rats of the LPS and LPS+ENL groups within 15 min, then, ENL without cell components (5 ml/kg) was infused at the speed of 0.5 ml per minute in the LPS+ENL group, the same amount of saline was administered in the LPS group. The rats in the sham group received the same surgical procedure and saline. The histomorphology and the levels of P-selectin, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) in pulmonary tissue were assessed. LPS induced pulmonary injury as well as increased the wet/dry weight ratio (W/D) and the levels of P-selectin, ICAM-1, and MPO in pulmonary tissues. These deleterious effects of LPS were significantly ameliorated by ENL treatment. Exogenous normal lymph could markedly alleviate the acute lung injury induced by lipopolysaccharide, and its effects might be related to lessening the adhesion molecules.(AU)

Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

Effect of ischemia preconditioning on renal ischemia/reperfusion injury in rats

To study the effect of ischemia preconditioning (IP) on renal ischemia/reperfusion (I/R)-associated functional injury and expression of renal adhesion molecules in rats.

The ischemia preconditioning plan adopted in this experiment involved renal warm ischemia for 6 min. and blood flow for 4 min., repeated four times. The Wistar rat kidneys used for warm ischemia preconditioning were subjected to 60 min of renal warm ischemia followed by reperfusion. The rat kidneys with ischemia/reperfusion were compared with the ischemia preconditioning group to observe rat renal function and changes in the expression of renal adhesion molecules ICAM-1, P--Selectin, and E-Selectin.

The expression of rat renal adhesion molecules (ICAM-1, P-Selectin, and E-Selectin) with ischemia preconditioning was significantly lower than that of the ischemia/reperfusion group. Serum creatinine was significantly lower than that in the ischemia/reperfusion group after 48 hours.

Ischemia preconditioning has a protective effect on renal function. Reduced expression of renal adhesion molecules is likely a mechanism involved in the observed protection. .

Expression of RANTES, eotaxin-2, ICAM-1, LFA-1 and CCR-3 in chronic rhinosinusitis patients with nasal polyposis / Expressão de RANTES, eotaxina-2, ICAM-1, LFA-1 e CCR-3 em pacientes com rinossinusite crônica associada à polipose nasossinusal

PURPOSE: To compare gene expression of the chemokines RANTES and eotaxin-2, its receptor, CCR-3, adhesion molecule ICAM-1 and its receptor LFA-1 in eosinophilic polyps and in control normal nasal mucosa. METHODS: Gene expression was quantified by Real Time PCR in polyps (n=35) and in healthy nasal mucosa (n=15). RESULTS: Eosinophilic polyps showed a higher expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa. CONCLUSION: Eosinophilic polyps present greater expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa.

OBJETIVO: Comparar a expressão gênica das quimiocinas RANTES e eotaxina-2, do seu receptor CCR-3, da molécula de adesão ICAM-1 e do seu receptor LFA-1 entre pólipos nasais eosinofílicos (PE) (n=35) e mucosa nasal controle (n=15). MÉTODOS: Quantificou-se a expressão gênica dos mediadores citados pela técnica de PCR em tempo real em PEs e em mucosas de concha média de pacientes sem doenças nasais ou alteração endoscópica. RESULTADOS: Pólipos eosinofílicos apresentam maior expressão de eotaxina-2 e RANTES, mas não de CCR-3, ICAM-1 e LFA-1, quando comparados as mucosas nasais controles. CONCLUSÃO: Pólipos eosinofícios apresentaram maior expressão de eotaxin-2 and RANTES, mas não de CCR-3, ICAM-1 ou LFA-1,comparada à mucosa nasal controle.

Expression of RANTES, eotaxin-2, ICAM-1, LFA-1 and CCR-3 in chronic rhinosinusitis patients with nasal polyposis / Expressão de RANTES, eotaxina-2, ICAM-1, LFA-1 e CCR-3 em pacientes com rinossinusite crônica associada à polipose nasossinusal

PURPOSE: To compare gene expression of the chemokines RANTES and eotaxin-2, its receptor, CCR-3, adhesion molecule ICAM-1 and its receptor LFA-1 in eosinophilic polyps and in control normal nasal mucosa. METHODS: Gene expression was quantified by Real Time PCR in polyps (n=35) and in healthy nasal mucosa (n=15). RESULTS: Eosinophilic polyps showed a higher expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa. CONCLUSION: Eosinophilic polyps present greater expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa.(AU)

OBJETIVO: Comparar a expressão gênica das quimiocinas RANTES e eotaxina-2, do seu receptor CCR-3, da molécula de adesão ICAM-1 e do seu receptor LFA-1 entre pólipos nasais eosinofílicos (PE) (n=35) e mucosa nasal controle (n=15). MÉTODOS: Quantificou-se a expressão gênica dos mediadores citados pela técnica de PCR em tempo real em PEs e em mucosas de concha média de pacientes sem doenças nasais ou alteração endoscópica. RESULTADOS: Pólipos eosinofílicos apresentam maior expressão de eotaxina-2 e RANTES, mas não de CCR-3, ICAM-1 e LFA-1, quando comparados as mucosas nasais controles. CONCLUSÃO: Pólipos eosinofícios apresentaram maior expressão de eotaxin-2 and RANTES, mas não de CCR-3, ICAM-1 ou LFA-1,comparada à mucosa nasal controle.(AU)

Correlação entre mediadores inflamatórios na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior por vírus sincicial respiratório e a gravidade da doença / Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity

OBJETIVO: Avaliar se as concentrações dos mediadores inflamatórios (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 e IL-10) na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior (ITRI) por vírus sincicial respiratório (VSR) apresentam correlação com os marcadores clínicos de gravidade da doença. MÉTODOS: Entre julho de 2004 e dezembro de 2005, 30 crianças com idade inferior a três meses, diagnosticadas com ITRI por VSR e admitidas em uma UTI neonatal foram incluídas neste estudo. RESULTADOS: Houve uma correlação positiva significante entre a gravidade da doença na admissão hospitalar, determinada por um sistema de escore clínico modificado, e as concentrações de sICAM-1 e de IL-10 na secreção nasofaríngea e de IL-6 no soro dos pacientes. Houve também uma correlação positiva significante entre a concentração de IL-6 no soro e o tempo de oxigenoterapia e a duração da internação. CONCLUSÕES: As concentrações de sICAM-1 e IL-10 na secreção nasofaríngea e de IL-6 no soro determinadas na admissão poderiam ser usadas como marcadores de gravidade da ITRI por VSR. Os níveis de IL-6 determinados no soro na admissão também poderiam ser usados para predizer o prolongamento da oxigenoterapia e da duração da internação.

OBJECTIVE: To determine whether the concentrations of inflammatory mediators (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 and IL-10) in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) correlate with the clinical markers of disease severity. METHODS: Between July of 2004 and December of 2005, 30 children less than three months of age, diagnosed with LRTI caused by RSV and admitted to a neonatal ICU, were included in this study. RESULTS: The severity of disease at hospital admission, as determined with a modified clinical scoring system, presented a significant positive correlation with sICAM-1 and IL-10 concentrations in the nasopharyngeal secretion, as well as with IL-6 concentrations in the serum, of the patients. In addition, serum IL-6 concentrations presented a significant positive correlation with the duration of oxygen therapy and with the length of hospital stay. CONCLUSIONS: At hospital admission, the concentrations of sICAM-1 and IL-10 in the nasopharyngeal secretion, as well as the concentration of IL-6 in the serum, could be used as markers of severity in patients with LRTI caused by RSV. The serum levels of IL-6 determined at admission could also be used to predict prolonged oxygen supplementation and hospital stay.

Blockage of intercellular adhesion molecule-1 (ICAM-1) in the prevention of reperfusion lesion in the skeletal musculature of EPM-1 Wistar rats

Purpose: Ischemia-reperfusion lesions are a form of acute inflammation in which leukocytes are considered to play a pivotal role. This study was made with the objective of determining whether the blockage of intracellular adhesion molecule-1, involved in the diapedesis of leukocytes, is efficacious in minimizing this lesions in the skeletal musculature of the posterior limbs of rats. Methods: The juxta-infrarenal aorta of three groups of six adult rats was clipped for six hours. After this, one group was sacrificed (control group) and the others underwent 24 hours of reperfusion, one with 0.9% physiological saline (reperfusion group) and the other with anti-ICAM-1 monoclonal antibodies (ICAM-1 group). A myeloperoxidase assay was utilized for estimating the infiltrate of neutrophils. Biopsies were obtained to make thin sections of hematoxylin-eosin and NADH. Blood samples were collected for making assays of biochemical parameters (creatinine; potassium; DHL; leukogram; venous pH; CK). Results: The myeloperoxidase levels were raised in the reperfusion (p 0.001) and ICAM-1 (p 0.019) groups in relation to the control group. The oxidative activity of the muscle fibers was significantly raised in the groups that underwent reperfusion. The other parameters did not present significant differences. Conclusions: The reperfusion lesion was bigger than the ischemic lesion. There was an increase in oxidative activity and inflammatory infiltrate with the reperfusion, without significant muscle necrosis being seen under the optical microscope. The blockage of ICAM-1 diminished the inflammatory infiltrate but not the rise in oxidative activity observed with the reperfusion.

Objetivo: As lesões de isquemia-reperfusão (I/R) são uma forma de inflamação aguda na qual os leucócitos são considerados como tendo um papel fundamental. Este estudo foi feito com o objetivo de determinar se o bloqueio das Moléculas de Adesão Intercelular -1 (ICAM-1), envolvidas na diapedese dos leucócitos, é eficaz em minimizar estas lesões na musculatura esquelética dos membros posteriores de ratos. Métodos: A aorta infra-renal de três grupos de seis ratos adultos foi clampeada por seis horas. Logo após, um grupo foi sacrificado (grupo controle) e os outros foram submetidos a 24 horas de reperfusão, um com solução salina fisiológica 0,9% (grupo reperfusão) e outro com anticorpos monoclonais anti-ICAM-1 (grupo ICAM-1). A quantificação da enzima mieloperoxidase foi utilizada para estimar o infiltrado de leucócitos na musculatura. Biópsias foram obtidas e coradas com hematoxilina-eosina e NADH. Amostras de sangue foram obtidas e parâmetros bioquímicos foram analisados (creatinina; potássio; DHL; leucograma; pH venoso, CK). Resultados: Os níveis de mieloperoxidase foram aumentados nos grupos reperfusão (p 0,001) e ICAM-1 (p 0,019) em relação ao grupo controle. A atividade oxidativa das fibras musculares foi aumentada de maneira significativa nos grupos submetidos a reperfusão. Os outros parâmetros não apresentaram diferenças significativas. Conclusões: A lesão de reperfusão foi de maior magnitude que a lesão isquêmica. Houve aumento da atividade oxidativa e do infiltrado inflamatório com a reperfusão, não se observando necrose significativa da musculatura com o microscópio óptico. O bloqueio de ICAM-I diminuiu o infiltrado inflamatório mas não o aumento da atividade oxidativa observado com a reperfusão.