Mechanical disfunction in the mucosal oedema formation of patients with nasal polyps.

BACKGROUND: Nasal polyposis (NP) is characterized by an anomalous tissue growth with oedema and a lack of extracellular matrix. In this study, we investigated whether a mechanical disfunction of the forces that act in oedema formation is present in NP. METHODS: We compared the interstitial hydrostatic pressure behaviour during a saline solution infusion between healthy nasal mucosa (inferior and middle turbinate from 10 patients) and inflamed nasal mucosa from NP patients (inferior, middle turbinate and a nasal polyp from 6 patients). We used Controlled Disc Stimulation equipment to compare the curve Pressure/Volume created during the saline solution infusion. RESULTS: The pressure at 0.2 ml infusion was lower in the middle turbinate of NP patients than in the middle turbinate of control patients. The lowest P/V mean assessed was in the polypoid tissue. CONCLUSIONS: The interstitial hydrostatic pressure showed different behaviour during liquid infusion in nasal mucosa from NP patients when compared with healthy nasal mucosa. This study allows us to cogitate on a new pathophysiological mechanism contributing to the development of the NP.

Role of imbalance of eicosanoid pathways and staphylococcal superantigens in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a multifactorial disease of the upper airways with a high prevalence (approximately 11%) in the general population. Different immune and inflammatory mechanisms are involved in its pathogenesis. Alterations in the arachidonic acid pathway (leading to an imbalanced production of eicosanoids) have been linked to the pathophysiology of different diseases especially nasal polyposis, asthma, and aspirin-exacerbated respiratory disease. Furthermore, viral and bacterial infections have been identified as important factors amplifying the pro-inflammatory reactions in these pathologies. This review summarizes the impact of an imbalance in the eicosanoid pathway and the effect of Staphylococcus aureus enterotoxins on the regulation of the pro-inflammatory network in CRS and their translation into disease severity.

Prevalence of chronic rhinosinusitis in Sao Paulo.

INTRODUCTION: Studies designed to investigate chronic rhinosinusitis (CRS) epidemiology play an important role to assess population`s distribution and risk factors to result in the development and promotion of public health policies. METHOD: This study design is a survey carried out with a complex two-stage cluster sampling plan. Personal interviews were carried out with 2,003 individuals. The questionnaire included the epidemiological criteria for CRS. Demographic data, history of physician-diagnosed respiratory diseases (asthma, sinusitis, rhinitis), smoking, family income, educational attainment, and household characteristics were also evaluated. RESULTS: The overall response rate was 93.9% of the households. Mean age was 39.8 +- 21 years; 45.33% were male. The overall prevalence of CRS in the city of Sao Paulo was 5.51%. We found a significant association between diagnosis of CRS and diagnosis of asthma and CRS and diagnosis of rhinitis and a significant association between presence of CRS and belonging to the low-income subgroup. CONCLUSION: The municipality of Sao Paulo has an urban population of 11 million. According to the present study, the prevalence of CRS is 5.51%, which represents more than 500,000 individuals affected by this condition in the city.

Influence of phosphorus on Cu sorption kinetics: stirred flow chamber experiments.

A stirred flow reactor was used to study the influence of phosphorus on the adsorption and desorption kinetics of copper in two acid soils on granite and amphibolite. The presence of P was found to significantly increase Cu adsorption in both soils, albeit at different types of sites (mainly in slow adsorption sites in the soil on granite, and both in fast and slow adsorption sites in that on amphibolite). The increased Cu sorption at fast sites in the amphibolite soil was due to its high content in Fe oxyhydroxides, which bound P and released OH(-) as a result, thereby raising the pH and leading to a higher sorption capacity during fast reactions. On the other hand, the increased Cu sorption at slow adsorption sites was due to Cu(2+) acting as a bridging element between P and organic matter.

Clinical and immunological determinants of severe/refractory asthma (SRA): association with Staphylococcal superantigen-specific IgE antibodies.

BACKGROUND: Demographic and immunological determinants of severe refractory asthma (SRA) are not well characterized. Because Staphylococcus aureus enterotoxins with superantigenic activity have been associated with upper and lower airway inflammation, we aimed to evaluate the association of sensitization to Staphylococcal enterotoxins with asthma severity and various asthma phenotypes. METHODS: The study included 109 patients with SRA diagnosed according to the American Thoracic Society Workshop 2000, and 101 patients with nonsevere asthma, followed for at least 12 months. Specific IgE to Staphylococcus enterotoxins and total IgE and eosinophil cationic protein concentrations were measured in serum with immunoassays. FINDINGS: A significant risk for severe asthma was associated with female gender [Odds Ratio (OR) = 2.04], history of wheezing in childhood (OR = 2.47), presence of hypersensitivity to aspirin (OR = 1.96) and with body mass index (OR = 3.08). The mean level of enterotoxin-specific IgE was 3-fold higher in patients with severe asthma when compared to patients with nonsevere asthma (P = 0.01). Serum-specific IgE to enterotoxins was significantly associated with low respiratory function parameters (FEV1, FEV1/FVC and MEF 25/75) and increased airway reversibility in response to albuterol. The presence of specific IgE to enterotoxin carried a significant risk for patients to have serum total IgE level above 100 kU/l (OR = 7.84). INTERPRETATION: Specific immunological response to enterotoxins is associated with clinical and immunological parameters of asthma severity, suggesting a role for Staphylococcal enterotoxins in the asthma pathogenesis.

T cell inflammatory response, Foxp3 and TNFRS18-L regulation of peripheral blood mononuclear cells from patients with nasal polyps-asthma after staphylococcal superantigen stimulation.

BACKGROUND: Staphylococcal superantigens may modulate airway inflammatory disease. OBJECTIVE: We assessed the effect of Staphylococcus aureus enterotoxin B (SEB) on T cell activation in patients with nasal polyps and asthma, and its possible link to aspirin hypersensitivity. METHODS: Leucocytes were isolated from five healthy subjects (controls), five asthmatics with nasal polyps without (NP-ATA) and five with aspirin-induced asthma (NP-AIA). Cells were incubated with increasing concentrations of SEB for 4 and 18 h. Release of T(H)1/T(H)2 cytokines was assessed by Cytometric Bead-Array. Foxp3 and TNFRS18-L expression were analysed by qPCR and flow cytometry. RESULTS: After 4 and 18 h, SEB significantly increased IFN-gamma, IL-4, TNF-alpha, IL-5 and IL-2 concentrations in supernatants of both NP polyp groups compared with controls. Baseline Foxp3 was significantly decreased in both NP-asthma groups. Incubation with SEB for 4 h induced a limited up-regulation of Foxp3 in NP-AIA patients, which was switched off consecutively. Foxp3 was significantly up-regulated in the control group after 18 h, but not in the NP-asthmatic groups. In parallel, TNFRS18-L mRNA significantly increased after 18 h in the NP-asthma groups compared with control subjects. This molecule was highly expressed in CD11c(+)CD14(+) cells and its levels increased after 18 and 24 h culture in the NP-asthma patients. CONCLUSION: SEB induces both T(H)1 and T(H)2 pro-inflammatory responses in patients with nasal polyps and asthma regardless of the presence of aspirin hypersensitivity. The nature of this response may be linked to a basal deficiency of Foxp3 observed in the NP-asthmatic patients and/or to the up-regulation of TNFRS18-L on monocytes/dendritic cell precursors.

CRTH2 mediates the activation of human Th2 cells in response to PGD(2) released from IgE/anti-IgE treated nasal polyp tissue.

BACKGROUND: Mast cells release mediators upon stimulation that contribute to the pathogenesis of chronic airway disease, including the recruitment and activation of Th2 lymphocytes. The objective was to determine the involvement of prostaglandin D(2) (PGD(2)) and its receptors in the chemotaxis of Th2 cells, using nasal polyp tissue. METHODS: Tissue explants from ten patients with nasal polyposis were incubated with RPMI alone or RPMI containing IgE/anti-IgE for 30 min. Some samples were treated with diclofenac to inhibit the production of PGD(2). Supernatants were assayed for PGD(2) content and for their ability to promote human Th2 cell chemotaxis in the presence and absence of a CRTH2 antagonist. Transcript levels of D protanoid receptor type 1 (DP(1)), chemoattractant receptor-homologous receptor expressed on Th2 cells (CRTH2) and PGD(2) synthase were analysed by real time PCR. RESULTS: Increased release of PGD(2) by nasal polyp tissue treated with IgE/anti-IgE was significantly inhibited by preincubation of the tissue with diclofenac. Transcript levels of PGD(2) synthase, DP(1) and CRTH2 receptors increased after stimulation with IgE/anti-IgE. Supernatants from IgE/anti-IgE-stimulated nasal polyp tissue caused significantly increased chemotaxis of Th2 cells. The levels of PGD(2) produced and the degree of Th2 cell chemotaxis were highly correlated. Diclofenac inhibited the production of Th2 cell chemotactic activity, and the chemotactic effect of the supernatant on Th2 cells was inhibited by the CRTH2 antagonist ramatroban. CONCLUSION: These data suggest that in immunologically activated nasal polyp tissue, PGD(2) produced by mast cells promotes the migration of Th2 cells through a CRTH2 dependent mechanism.

Copper fractionation and release from soils devoted to different crops.

We studied copper release as a function of pH in eight samples of acid soils under vine and maize crops containing variable concentrations of total copper (Cu(t)) from 55 to 112 mg kg(-1). Although both types of soil had similar Cu(t) values, the origin of the copper was essentially anthropogenic in the vineyard soils and natural (as result of weathering of parent material) in those under maize. The disparate origin of the metal resulted in marked differences in its fractions, particularly as regards organically bound copper, which was much more abundant in the vineyard soils. This had a strong effect on copper release as a function of pH, which was one order of magnitude greater in the vineyard soils than in those under maize.

Inflamed intestinal mucosa features a specific epithelial expression pattern of indoleamine 2,3-dioxygenase.

Indoleamine 2,3-dioxygenase (IDO) catalyzes the first step in the degradation of tryptophan, an essential amino acid. During inflammation IDO can be induced in different cell types resulting in local tryptophan depletion. This inhibits T cell proliferation and may induce apoptosis. High expression of IDO was previously found in inflammatory bowel disease and is thought to represent a mechanism for downregulation of the local immune response. Our aim is to investigate the expression pattern of IDO in normal and inflamed murine and human intestinal mucosa. Immunohistochemical staining for IDO was performed on paraffin sections of colon of two mouse models for colitis and their controls and on paraffin sections of human ileum and colon in normal and two different inflammatory conditions, namely inflammatory bowel disease and diverticulitis. IDO immunohistochemistry showed similar results in murine and human tissue. In normal, as well as in inflamed mucosa, some mononuclear cells, fibroblasts and endothelial cells were positive for IDO. In inflamed mucosa a specific expression pattern of epithelial IDO was found where epithelial cells flanking ulcers or bordering crypt abscesses showed high IDO expression. Moreover, in human intestinal inflammation, IDO was expressed in ulcer associated cell lineage. Since bacterial invasion is more pronounced in erosions and in crypt abscesses and since IDO activity and the resulting local tryptophan depletion can cause growth arrest of several tryptophan-dependent microorganisms, IDO expression in the vicinity of interruptions of the epithelial barrier may point to a role for IDO as a local anti-infectious agent. Furthermore, expression of IDO at the margin of ulcerations and in the reparative ulcer-associated cell lineage suggests involvement of IDO in repair processes.

Influence of organic matter removal on competitive and noncompetitive adsorption of copper and zinc in acid soils.

We studied competitive and noncompetitive adsorption of copper and zinc in four acid soils, and compared the behavior of the two metals in untreated samples and samples treated with hydrogen peroxide to remove organic matter in the soil. Copper exhibited stronger competitive adsorption than zinc in the untreated samples. However, removal of organic matter reduced copper adsorption to a greater extent than zinc adsorption, the two metals exhibiting a more similar adsorption pattern than the untreated samples. The presence of copper dramatically reduced zinc competitive adsorption in untreated samples; on the other hand, that of zinc only resulted in slightly reduced competitive adsorption of copper. The hydrogen peroxide treatment decreased competitive adsorption in both metals; however, copper continued to be more efficient than zinc in competing for binding sites on adsorbing surfaces. Desorption of Cu occurred much less readily than desorption of Zn and hysteresis is apparent especially for Cu.

An update on the impact of Staphylococcus aureus enterotoxins in chronic sinusitis with nasal polyposis.

Nasal polyps in adults, characterized by abundant eosinophils, local overproduction of immunoglobulin E, and often associated with asthma, have been appreciated as an eosinophilic inflammation, potentially of allergic origin, but unrelated to a bacterial impact. Evidence accumulates, however, that Staphylococcus aureus colonizes chronic rhinosinusitis with, but not without polyps, with significantly increased prevalence. The germs release enterotoxins, which act as superantigens and induce a topical multiclonal IgE-formation as well as a severe, possibly steroid-insensitive eosinophilic inflammation. Recently, S. aureus could be demonstrated to reside intraepithelially, and potentially to release superantigens into the tissue from within the epithelial cells. An immune defect, either in the innate or adaptive immunity, might be responsible for this phenomenon. Follicle-like structures and lymphocyte accumulations, specifically binding enterotoxins, can be found within the polyp tissues, giving rise to local IgE formation. The superantigen-induced immune response also leads to a modulation of the severity of the eosinophilic inflammation, and may be linked to lower airway co-morbidity in polyp patients. Interestingly, IgE antibodies to enterotoxins can be found in the majority of aspirin-sensitive polyp tissues, associated with a substantial increase in ECP and IL-5. The possible role of S. aureus enterotoxins in polyp disease in Europe, the US and Asia has meanwhile been supported by several studies, demonstrating the presence of IgE antibodies to enterotoxins and inflammatory consequences in nasal polyp tissue. First studies also point to an involvement of S. aureus derived enterotoxins in lower airway disease, such as severe asthma and exacerbated COPD, clearly suggesting a clinical need for diagnosis and treatment of the germ and its related effects. Therapeutic approaches are so far empirical, and need further study, also serving to proof the clinical relevance of the concept.

Adsorption and desorption of copper and zinc in the surface layer of acid soils.

The environmental and health effects of the contamination of soils by heavy metals depend on the ability of the soils to immobilize these contaminants. In this work, the adsorption and desorption of Cu and Zn in the surface layers of 27 acid soils were studied. Adsorption of Cu(II) from 157-3148 mumol L(-1) solutions was much greater than adsorption of Zn(II) from solutions at the same concentration. For both Cu and Zn, the adsorption data were fitted better by the Freundlich equation than by the Langmuir equation. Multiple regression analyses suggest that Cu and Zn adsorption depends to a significant extent on pH and CEC: for both metals these variables accounted for more than 80% of the variance in the Freundlich pre-exponential parameter K(F), and pH also accounted for 57% of the variance in 1/n for Zn and, together with carbon content, for 41% of the variance in 1/n for Cu. The percentage of adsorbed metal susceptible to desorption into 0.01 M NaNO3 was greater for Zn than for Cu, but in both cases depended significantly on pH, decreasing as pH increased. In turn, both pH(H2O) and pH(KCl) are significantly correlated with cation exchange capacity. Desorption of metal adsorbed from solutions at relatively low concentration (787 mumol L(-1)) exhibited power-law dependence on Kd, the quotient expressing distribution between soil and soil solution in the corresponding adsorption experiment, decreasing as increasing Kd reflected increasing affinity of the soil for the metal. The absence of a similarly clear relationship when metal had been adsorbed from solutions at relatively high concentration (2361 mumol L(-1)) is attributed to the scant between-soil variability of Kd at these higher concentrations. In general, adsorption was greater and subsequent desorption less in cultivated soils than in woodland soils.