Impact of gut passage and mucus secretion by the earthworm Lumbricus terrestris on mobility and speciation of arsenic in contaminated soil

Earthworms inhabiting arsenic contaminated soils may accelerate the leaching of As into surface and ground waters. We carried out three experiments to determine the impact of passage of As contaminated soil (1150 mgAs kg−1) through the gut of the earthworm Lumbricus terrestris on the mobility and speciation of As and the effects of earthworm mucus on As mobility. The concentration of water soluble As in soil increased (from 1.6 to 18 mg kg−1) after passage through the earthworm gut. Casts that were aged for 56 days still contained more than nine times greater water soluble As than bulk earthworm inhabited soil. Changes were due to increases in As(V) mobility, with no change in As(III). Dilute mucus extracts reduced As mobility through the formation of As-amino acid-iron oxide ternary complexes. More concentrated mucus extracts increased As mobility. These changes, together with those due to the passage through the gut, were due to increases in pH, phosphate and soluble organic carbon. The mobilisation of As from contaminated soils in the environment by cast production and mucus secretion may allow for accelerated leaching or uptake into biota which is underestimated when bulk soil samples are analysed and the influence of soil biota ignored.

Effects of limonene and essential oil from Citrus aurantium on gastric mucosa: Role of prostaglandins and gastric mucus secretion

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The contribution of A3 adenosine receptor signaling to pulmonary inflammation and mucus secretion in the mouse

Adenosine has been implicated in chronic lung diseases such as asthma and COPD. Most physiological actions of adenosine are mediated through G-protein coupled adenosine receptors. Four subtypes of adenosine receptors have been identified, A1, A2A, A2B, and A 3. However, the specific roles of the various adenosine receptors in processes central to asthma and COPD are not well understood in part due to the lack of adequate animal models that examine the effect of adenosine on the development of lung disease. In this study we have investigated the expression and function of the A3 adenosine receptor in pulmonary eosinophilia and mucus production/secretion in adenosine deaminase (ADA)-deficient mice in which adenosine levels are elevated. ADA-deficient mice develop features of asthma and COPD, including lung eosinophilia and mucus hyperplasia in association with elevated lung adenosine levels. The A3 receptor was found to be expressed in eosinophils and mucus producing cells in the airways of ADA-deficient. Disruption of A3 receptor signaling in ADA-deficient mice by genetic removal of the receptor or treatment with MRS 1523, a selective A3 adenosine receptor antagonist, prevented airway eosinophilia and mucus production. Although eosinophils were decreased in the airways of ADA-deficient mice with disrupted A3 receptor signaling, elevations in circulating and lung interstitial eosinophils persisted, suggesting signaling through the A3 receptor is needed for the migration of eosinophils into the airways. Further examination of the role of the A3 receptor in mucus biology demonstrated that the A3 receptor is neither required nor is overexpression of the receptor in clara cells sufficient for mucus production in naive mice. Transgenic overexpression of the A3 receptor did elucidate a role for the A3 receptor in the secretion of mucus into the airways of ovalbumin challenged mice. These findings identify an important role for the A3 adenosine receptor in regulating lung eosinophilia and mucus secretion in inflammatory lung diseases. Therefore, the A3 adenosine receptor may represent a novel therapeutic target for the treatment and prevention of asthma. ^

Regulation of mucus secretion by cells isolated from the rat gastric mucosa

     This study was undertaken to further understanding of the mechanisms which regulate mucus secretion by rat stomach cells. Particular objectives were: (i) to develop and use a radiochemical assay to estimate the secretion of mucin by a suspension of gastric mucosal cells in vitro, (ii) to develop and use a solid-phase enzyme immunoassay (EIA) to study the regulation of the release of bulk gastric mucin from the isolated cells and (iii) to compare the results obtained with the two procedures.      Cells were isolated by exposure of gastric mucosa to pronase and EDTA. Cell suspensions were preincubated with D-[6-3H]glucosamine. [3H]-labelled material of high molecular mass released into the incubation medium, was purified by Fast Protein Liquid Chromatography, and appeared to be gastric mucin. Some unidentified [3H]-labelled material of lower molecular mass was also found in the medium. Release of [3H]-labelled high molecular mass material was essentially linearly related to time. Secretin, isoprenaline and carbachol stimulated release of [3H]-labelled high molecular mass material. The half-maximally effective concentrations of secretin and isoprenaline were 2.3nM and 34nM respectively. Histamine, gastrin and epidermal growth factor were without effect.      A rabbit polyclonal antibody was raised by using purified 'native' rat gastric mucin as immunogen. The antibody preparation appeared specific for rat gastric mucin and was used to establish a quantitative solid-phase EIA. Release of bulk mucin was essentially linearly related to time. Phorbol-12-myristate-13-acetate (PMA), forskolin and A23187 dose-dependently stimulated bulk mucin release. Synergistic interactions were observed between PMA and forskolin, and PMA and A23187. Secretin and isoprenaline were confirmed as mucin secretogogues.      In conclusion gastric mucin release was investigated for the first time by using a suspension of gastric mucosal cells. Two different assay procedures were developed. Some pathways and agents responsible for controlling mucin secretion were identified.

Endothelin A receptor antagonist modulates lymphocyte and eosinophil infiltration, hyperreactivity and mucus in murine asthma

Levels of endothelins are particularly high in the lung, and there is evidence that these peptides are involved in asthma. Asthma is a chronic inflammatory disease associated with lymphocyte infiltration. In the present study, we used a murine model of asthma to investigate the role of endothelins in lymphocyte and eosinophil infiltration into the airway hyperreactivity and mucus secretion. Sensitized C57B1/6 mice were treated with endothelin ET(A) receptor antagonist (BQ123) or endothelin ET(B) receptor antagonist (BQ788) 30 min before an antigen aerosol challenge. After 24 h, dose response curves to methacholine were performed in isolated lungs, FACS analysis of lymphocytes and eosinophil counts were performed in bronchoalveolar lavage fluid and mucus index was determined by histopathology. In sensitized and antigen-challenged mice there is a marked increase in the T CD(4)(+), T CD(8)(+), B220(+), T gamma delta(+) and NK1.1(+) lymphocyte subsets. Treatment with BQ123 further increased these cell populations. The number of eosinophils, airway hyperreactivity and mucus were all reduced by BQ123 treatment. The BQ788 had no significant effect on the parameters analyzed. Treatment with BQ123 reduced the endothelin concentration in lung homogenates, suggesting that endothelins exert a positive feedback on their synthesis. We show here that in murine asthma the ET(A) receptor antagonist up-regulates lymphocyte infiltration and reduces eosinophils, hyperreactivity and mucus. (C) 2008 Elsevier B.V. All rights reserved.

Oral Azithromycin for Treatment of Posterior Blepharitis

Purpose: To evaluate the effects of oral azithromycin in patients with posterior blepharitis. Methods: Twenty-six eyes of 13 patients with posterior blepharitis diagnosed by a qualified ophthalmologist were enrolled in this study. Patients were instructed to use oral azithromycin 500 mg per day for 3 days in 3 cycles with 7-day intervals. Subjective clinical outcomes were graded and scored 1 day before and 30 days after the end of the treatment (53 days after initiating the treatment) based on severity scores of: (1) eyelid debris; (2) eyelid telangiectasia; (3) swelling of the eyelid margin; (4) redness of the eyelid margin; and (5) ocular mucus secretion. For the assessment of global efficacy, patients were asked by the investigator to rate the subjective symptoms (eyelid itching, ocular itching, eyelid hyperemia, ocular hyperemia, ocular mucus secretion, photophobia, foreign body sensation, and dry eye sensation) on a scale of 0 (no symptoms) to 5 (severe symptoms). Break-up time, Schirmer I test, corneal fluorescein staining score, and rose bengal staining score were also performed in all patients. Results: All clinical outcomes scoring showed statistically significant improvement after oral azithromycin, except for eyelid swelling. Average subjective symptom grading improved statistically after treatment with oral azithromycin, except for eyelid hyperemia, photophobia, and foreign body sensation. Average tear film break-up time values showed statistically significant improvement after the treatment with oral azithromycin. No statistically significant improvement was observed on average values of Schirmer I test, corneal fluorescein staining score, and rose bengal staining score. Conclusions: The combination of multiple clinical parameters shown in this study supports the clinical efficacy of pulsed oral azithromycin therapy for the management of posterior blepharitis.

Lectin histochemical aspects of the ovarian lamellae epithelium of Genypterus blacodes (Schneider, 1801)

The composition and distribution of the glycoconjugates (GCs) secreted by the epithelium of ovarian lamellae with reference to the reproductive biology of Genypterus blacodes (Schneider, 1801) through lectin hi stochemistry is here discussed. In this species, the epithelial cells that line the ovarian cavity presented sharp morphological variations along the reproductive cycle related to the mucus secretion that accompanies oocyte ma turation. During sp awning season, residues of mannose and N-acetylglucosamine were detected in the glycocalyx of those cells using lectinhistochemistry. N- acetylgalactosamine and fucose were also observed in the same zone. The greatest variations in the lectinhistochemical pattern were found in the apical cytoplasm composition in comparison to the basal zone of the cells. The results of the present study were discussed by comparing their possible functional implications.

Intestinal permeability in strongyloidiasis

The objective of the present study was to assess intestinal permeability in patients with infection caused by Strongyloides stercoralis. Twenty-six patients (16 women and 10 men), mean age 45.9, with a diagnosis of strongyloidiasis were evaluated. For comparison, 25 healthy volunteers (18 women and 7 men), mean age 44.9, without digestive disorders or intestinal parasites served as normal controls. Intestinal permeability was measured on the basis of urinary radioactivity levels during the 24 h following oral administration of chromium-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) expressed as percentage of the ingested dose. The urinary excretion of 51Cr-EDTA was significantly reduced in patients with strongyloidiasis compared to controls (1.60 ± 0.74 and 3.10 ± 1.40, respectively, P = 0.0001). Intestinal permeability is diminished in strongyloidiasis. Abnormalities in mucus secretion and intestinal motility and loss of macromolecules could explain the impaired intestinal permeability.

Influence of age on the development of immunological lung response in intrauterine undernourishment

Objective: We investigated the effect of intrauterine undernourishment on some features of asthma using a model of allergic lung inflammation in rats. The effects of age at which the rats were challenged (5 and 9 wk) were also evaluated. Methods: Intrauterine undernourished offspring were obtained from dams that were fed 50% of the nourished diet of counterparts and were immunized at 5 and 9 wk of age. They were tested for immunoglobulin E anti-ova titers (by passive cutaneous anaphylaxis), cell count in the bronchoal-veolar fluid, leukotriene concentration, airway reactivity, mucus production, and blood corticosterone and leptin concentrations 21 d, after immunologic challenge. Results: Intrauterine undernourishment significantly reduced the antigen-specific immunoglobulin E production, inflammatory cell infiltration into airways, mucus secretion, and production of leukotrienes B-4/C-4 in the lungs in both age groups compared with respective nourished rats. The increased reactivity to methacholine that follows antigen challenge was not affected by intrauterine undernourishment. Corticosterone levels increased with age in the undernourished rats` offspring, but not in the nourished rats` offspring. Undernourished offspring already presented high levels of corticosterone before inflammatory stimulus and were not modified by antigen challenge. Leptin levels increased with challenge in the nourished rats but not in the undernourished rats and could not be related to corticosterone levels in the. undernourished rats. Conclusion: Intrauterine undernourishment has a striking and age-dependent effect on the off spring, reducing lung allergic inflammation. (C) 2008 Elsevier Inc. All rights reserved.

Studies of gastric mucosa regeneration and safety promoted by Mouriri pusa treatment in acetic acid ulcer model

Ethnopharmacological Relevance: Mouriri pusa Gardn. (Melastomataceae) is a medicinal plant commonly used by people living in the Cerrado to treat gastrointestinal disturbances. This medicinal plant has shown intense gastroprotective action in rodent gastric lesion, but still there are no data about its healing effect on gastric mucosa.Aim of the Study: To evaluate the methanolic extract (MeOH) obtained from Mouriri pusa leaves for its effect on the cicatrisation process of gastric ulcer.Mterials and Methods: The healing effects on gastric ulcers inducted by subserosal injection of acetic acid were evaluated by macroscopic and microscopic measures, imunohistochemistry and cell counting in rats treated with MeOH extract of Mouriri pusa (250 mg/kg, p.o./daily) for 14 or 30 days. The toxicity of Mouriri pusa was also evaluated by body and organ weight measure and clinical biochemical parameters.Results: Mouriri pusa treatments lasting 14 and 30 days showed elevated mucus secretion (PAS) and thicker regenerative gastric mucosa, denoting increased cell proliferation, which was confirmed by PCNA immunohistochemical analysis. Moreover, there was important cell recruitment (neutrophils and mast cells) to the site of the ulcer, which is an important factor in ulcer healing. No toxic effect was observed in all parameters evaluated. Phenolic compounds present in the MeOH extract like tannins, flavonoids and epicatechin are the probable agents involved in the healing effects of this medicinal plant.Conclusions: These findings showed a potential effect of Mouriri pusa in increasing regeneration of damaged gastric mucosa with safety for human use. (C) 2007 Elsevier B.V. All rights reserved.

Qualea grandiflora, a Brazilian Cerrado medicinal plant presents an important antiulcer activity

Qualea grandiflora is one of the species widely used in folk medicine to treat gastric ulcers in Cerrado of the central region of Brazil. The hydroalcoholic extract of bark (HE) of Qualea grandiflora was investigated for their ability to prevent and heal lesions in the gastric mucosa. The oral administration of HE exhibited antiulcer activity decreasing the ulcerative index induced by HCl/ethanol solution, indomethacin/bethanechol and stress. In the Shay model, results showed that HE (p.o.) only reduced the severity of gastric lesions without effects on pH, gastric acidity or volume. When given by intraduodenal route, HE changed the pH, but did not modify the other parameters of the gastric juice. These data were in accordance with those obtained when HE was administered orally for 14 days after gastric ulcers were induced by acetic acid in rats. HE presented healing process in subacute gastric ulcer induced by acetic acid in rats. Moreover, histological examinations showed the simple columnar epithelium, lamina propria with simple branched tubular glandules with dilated lumen and large amounts of mucus secretion. Phytochemical investigation of HE led to the detection of terpenes, steroids, saponins, phenolic compounds and tannins in this extract, which may be involved in the observed activity. (c) 2005 Elsevier B.V.. All rights reserved.

The gastroprotective effect of the essential oil of Croton cajucara is different in normal rats than in malnourished rats

It has been shown previously that malnourished rats are resistant to acute gastric lesions but not to subchronic gastric ulceration. It also has been demonstrated that the essential oil obtained from the bark of Croton cajucara (Sacaca) has antiulcer properties. In the present study, the ability of this essential oil to prevent the formation of gastric ulcers in rats fed a diet with 17 % protein (normoproteic rats) or 6 % protein (malnourished rats) was investigated. At a dose of 100 mg/kg body weight, orally, the essential oil significantly reduced the gastric injury caused by indomethacin (25 % after 2 h and 70 % after 4 h) only in normoproteic rats. In the pylorus ligature model, the essential oil increased the pH and gastric volume, but decreased the total acid concentration in both groups when compared to the respective control group. The essential oil significantly increased prostaglandin E2 production in glandular cells by 50 % compared to the controls in both groups of rats. In addition, the amount of gastric mucus was two-fold higher in malnourished rats than in normoproteic rats. The present results show that the enhanced protective effect of essential oil in malnourished rats involved an increase in prostaglandin E2 production and mucus secretion, which are both factors that protect the gastric mucosa against damage. In agreement with this, malnourished rats always had a lower number of acute gastric ulcers.

Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and beta-pinene: Involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E-2

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Healing, Antioxidant and Cytoprotective Properties of Indigofera truxillensis in Different Models of Gastric Ulcer in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of Mouriri pusa tannins and flavonoids on prevention and treatment against experimental gastric ulcer

Aim of the study: Mouriri pusa, popularly known as manapuca or jaboticaba do mato, is a plant from Brazilian cerrado that has been found to be commonly used in the treatment of gastrointestinal disturbs in its native region. The present work was carried out to investigate the effect of tannins (TF) and flavonoids (FF) fractions from Mouriri pusa leaves methanolic extract on the prevention and cicatrisation process of gastric ulcers, and also evaluate possible toxic effects.Materials and methods: The following protocols were taken in rats: acute assay, in which ulcers were induced by oral ethanol after pre-treatment with the fractions; and 14 days treatment assay, in which ulcers were treated for 14 days after induction by local injection of acetic acid.Results: In the acute model, treatment with either, TF (25 mg/kg) or FF (50 mg/kg), was able to reduce lesion area, showing gastroprotective effect. In addition, FF proved itself anti-inflammatory by reducing COX-2 levels. In acetic acid model, both fractions exhibited larger ulcers' regenerative mucosa, indicating cicatrisation enhancement. FF group also showed augmented cell proliferation, anti-inflammatory action and enhanced angiogenesis as well as increased mucus secretion. Moreover, concerning the toxicity parameters analyzed, no alteration in the fractions groups was observed.Conclusions: Tannins and flavonoids from Mouriri pusa provide beneficial effects against gastric ulcers with relative safety. (C) 2010 Elsevier B.V. All rights reserved.