Evaluation of the anti-inflammatory action of curcumin analog (DM1): Effect on iNOS and COX-2 gene expression and autophagy pathways.

This work describes the anti-inflammatory effect of the curcumin-analog compound, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate (DM1), and shows that DM1 modulates iNOS and COX-2 gene expression in cultured RAW 264.7 cells and induces autophagy on human melanoma cell line A375.

Kinetoplastid Membrane Protein-11 as a Vaccine Candidate and a Virulence Factor in Leishmania.

Kinetoplastid membrane protein-11 (KMP-11), a protein present in all kinetoplastid protozoa, is considered a potential candidate for a leishmaniasis vaccine. In Leishmania amazonensis, KMP-11 is expressed in promastigotes and amastigotes. In both stages, the protein was found in association with membrane structures at the cell surface, flagellar pocket, and intracellular vesicles. More importantly, its surface expression is higher in amastigotes than in promastigotes and increases during metacyclogenesis. The increased expression of KMP-11 in metacyclic promastigotes, and especially in amastigotes, indicates a role for this molecule in the parasite relationship with the mammalian host. In this connection, we have shown that addition of KMP-11 exacerbates L. amazonensis infection in peritoneal macrophages from BALB/c mice by increasing interleukin (IL)-10 secretion and arginase activity while reducing nitric oxide production. The doses of KMP-11, the IL-10 levels, and the intracellular amastigote loads were strongly, positively, and significantly correlated. The increase in parasite load induced by KMP-11 was inhibited by anti-KMP-11 or anti-IL-10-neutralizing antibodies, but not by isotype controls. The neutralizing antibodies, but not the isotype controls, were also able to significantly decrease the parasite load in macrophages cultured without the addition of KMP-11, demonstrating that KMP-11-induced exacerbation of the infection is not dependent on the addition of exogenous KMP-11 and that the protein naturally expressed by the parasite is able to promote it. All these data indicate that KMP-11 acts as a virulence factor in L. amazonensis infection.

Effects of typified propolis on mutans streptococci and lactobacilli: a randomized clinical trial.

OBJECTIVE: The aim of this study was to determine in a randomized, double-blind, placebo-controlled clinical trial the effects of typified propolis and chlorhexidine rinses on salivary levels of mutans streptococci (MS) and lactobacilli (LACT). METHODS: One hundred patients were screened for salivary levels of MS >100,000 CFUs/mL of saliva. All patients presented with at least one cavitated decayed surface. Sixty patients met entry criteria. Subjects were adults 18-55 years old. After restoration of cavitated lesions patients were randomized to 3 experimental groups: 1) PROP-alcohol-free 2% typified propolis rinse (n = 20); 2) CHX- 0.12% chlorhexidine rinse; 3) PL-placebo mouthrinse. Patients rinsed unsupervised 15 mL of respective rinses twice a day for 1 min for 28 days. Patients were assessed for the salivary levels of MS (Dentocult SM) and LACT (Dentocult LB) at baseline, 7-day, 14-day, and at 28-day visits (experimental effects) and at 45-day visit (residual effects). General linear models were employed to analyze the data. RESULTS: PROP was superior to CHX at 14-day and 28-day visits in suppressing the salivary levels of MS (p < .05). PROP was superior to PL at all visits (p < .01). The residual effects of PROP in suppressing the salivary levels of MS could still be observed at the 45-day visit, where significant differences between PROP and CHX (p < .05), were demonstrated. PROP was significantly superior than CHX in suppressing the levels of salivary LACT at the 28-day visit (p < .05). CONCLUSION: Typified propolis rinse was effective in suppressing cariogenic infections in caries-active patients when compared to existing and placebo therapies.

Protection against cutaneous leishmaniasis by intranasal vaccination with lipophosphoglycan.

We previously showed the opposing effect of systemic and mucosal vaccination with whole Leishmania amazonensis antigen (LaAg). Here, the role played by lipophosphoglycan (LPG) as the key disease-promoting component of intramuscular (i.m.) LaAg and its usefulness as a defined intranasal vaccine was investigated in murine cutaneous leishmaniasis. BALB/c mice were twice vaccinated by the i.m. route with 25mug of intact LaAg or with LaAg that was pretreated with anti-LPG 3A1-La monoclonal antibody, prior to infection with L. amazonensis. LPG neutralization rendered the otherwise disease-promoting LaAg antigen protective, as observed by the smaller lesion sizes and reduced parasite burden. The increased resistance was accompanied by a markedly lower antigen-driven TGF-beta and IL-10 responses in the lesion-draining lymph nodes, concomitant with significantly higher IFN-gamma production. To test for intranasal efficacy, 10 microg of affinity-purified LPG and its parental LaAg were twice instilled in the nostrils prior to L. amazonensis infection. In both cases, similarly slower lesion growth and lower parasite burden were found that was associated with increased IFN-gamma and IL-10 responses in the lesion-draining lymph nodes. These results support a role for LPG in the dual route-related effect of LaAg and shows its strong potential as a defined needle-free and adjuvant-free vaccine for cutaneous leishmaniasis.

Pantoprazole treatment does not invoke anti-inflammatory properties in vivo.

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are antiulcer agents that have gastric antisecretory and mucosal protective actions. The antisecretory effect of these agents derives from the inhibition of gastric parietal cell proton pump H+/K+ ATPase. The exact mechanism of PPI-induced gastric mucosal protection is not known though. It has been suggested that PPI may accumulate, modulating the functions of neutrophils and, thus, may be useful in reducing the gastric mucosal injury caused by these cells. However, these same mechanisms may not be desirable when PPIs are prescribed in prophylaxis and pre-operatively for ill or immunodepressed patients. The present study was designed to examine a possible anti-neutrophil activity of pantoprazole in vivo. A short study with omeprazole and lanzoprazole was also performed. METHODS: Dosages of PPIs able to inhibit basal acid secretion (10 and 100 mg kg(-1)) were administered intraperitoneally (i.p.) to rats for 7 or 28 days. Cimetidine (100 mg kg(-1)) and dexamethasone (0.75 mg kg(-1)) were used as controls for antisecretory and anti-inflammatory activity, respectively. Air pouches were then developed in these animals, and Helicobacter pylori suspension or carrageenan was used as inflammatory stimulus. Exudate formation and leukocyte migration to air pouches were assessed. RESULTS: Neither short nor long treatment with pantoprazole modified the ability of neutrophils to migrate in response to carrageenan or H. pylori. The same results were obtained when omeprazole or lanzoprazole was used. Dexamethasone, alone, a potent anti-inflammatory drug, was able to reduce polymorphonuclear and mononuclear cell migration. CONCLUSION: Based on these observations, pantoprazole and other PPIs seem to have no anti-inflammatory properties in vivo.

Acute inflammatory response induced by Helicobacter pylori in the rat air pouch.

Infection by Helicobacter pylori elicits persistent neutrophil infiltration in the gastric mucosa and stimulates the release of substances that may contribute to the establishment of gastritis. In this study, we used the rat air pouch model to evaluate the acute inflammatory response to H. pylori, in vivo. A pronounced neutrophil infiltration was observed 6 h and 12 h after the injection of H. pylori into the air pouch. Strains with different genotypes were able to induce cellular influx. This response was dependent upon the amount of bacteria injected and still occurred when heat-killed bacteria were employed. An increase in prostaglandin E(2) levels was observed, indicating that H. pylori induced cyclooxygenase 2 in this model. The production of interleukin-1 beta and tumor necrosis factor-alpha by leukocytes was also enhanced, suggesting that this model may be useful for studying the direct activation of neutrophils by H. pylori in vivo.

TcArf1: a Trypanosoma cruzi ADP-ribosylation factor.

Arfs (ADP-ribosylation factors) are conserved GTP-binding proteins involved in the control of coatomers assembling in budding vesicles in the eukaryotic secretory pathway and during some endocytic events. Here, we describe the gene for an Arf-homologue from the unicellular kinetoplastid parasite Trypanosoma cruzi, named TcArf1. TcArf1 is present in a discrete copy number in the T. cruzi genome and is expressed as a 1-kb transcript in the three main life forms of the parasite. Increased mRNA expression in epimastigotes may correlate with abundant protein biosynthesis and endocytosis in this stage.