Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.

Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF) patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs) surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS).

A complex multilevel attack on Pseudomonas aeruginosa algT/U expression and algT/U activity results in the loss of alginate production.

Infection by the opportunistic pathogen Pseudomonas aeruginosa is a leading cause of morbidity and mortality seen in cystic fibrosis (CF) patients. This is mainly due to the genotypic and phenotypic changes of the bacteria that cause conversion from a typical nonmucoid to a mucoid form in the CF lung. Mucoid conversion is indicative of overproduction of a capsule-like polysaccharide called alginate.

Immunophenotypic pattern and cytokine profiles of dry type cutaneous leishmaniasis.

Background: Dry type localized cutaneous leishmaniasis, one of the most prevalent cutaneous parasitic infections in Kerman Province, is presented as a polarized disease in which cytokine profiles secreted by immune cells play a major role in its presentation. In order to clarify the idea, immunohistochemical study of skin biopsies were performed to elucidate the cytokine release capabilities of immune cells.

Methods: Skin biopsies of acute, chronic nonlupoid, and chronic lupoid recidivans lesions of dry type localized cutaneous leishmaniasis were studied by immunohistochemical staining methods for immunophenotypic patterns (CD4, CD8, CD14, CD19, CD56, CD11a, CD18, CD1a, HLA-DR, CD54) and cytokines (INF-gamma, IL-12, IL-4, TNF-alpha) released by immune inflammatory cells.

Pathology of post-kala-azar dermal leishmaniasis: a light microscopical, immunohistochemical, and ultrastructural study of skin lesions and draining lymph nodes.

Background: Whereas the clinical manifestations and treatment of post-kala-azar dermal leishmaniasis (PKDL) have been adequately described before, the pathology received little attention, particularly the African form of PKDL which shows some clinical differences from the disease in India. Therefore, our aim was to characterize the pathology and the immunohistopathology in PKDL lesions and correlate the histopathological findings with the clinical features of the disease.

Methods: Biopsies of skin lesions were examined for histopathological changes in formalin-fixed tissues and for cell phenotypes and adhesion molecules by immunohistochemistry.

Leishmania donovani: an in vitro study of antimony-resistant amphotericin B-sensitive isolates.

Drug sensitivity of clinically antimony-unresponsive Leishmania donovani isolates from Eastern Sudan was evaluated in an in vitro culture system against sodium stibogluconate (Pentostam) and Amphotericin B. Eight isolates, six from antimony-resistant and two from clinically responsive patients were included in the study. Parasites were tested as promastigotes and four of them were selected to be tested as amastigotes using a murine macrophage-like cell line.

Conformationally restricted anti-plasmodial chalcones.

Chalcones can exist as Z- or E-isomers and it is generally anticipated that both isomers are equipotent. In order to determine the active isomer of anti-plasmodial chalcones a series of analogues locked in the Z- or the E-form were prepared and evaluated for their anti-plasmodial activity. It was shown that the Z-locked analogue was nearly inactive, whereas the E-locked analogues were equipotent to the parent chalcones, indicating that the E-isomer is the active conformation.

[Ginseng modulates the immune response via its effect on cytokine production--secondary publication].

Ginseng has been shown to modulate the immune system. In this study, ginseng"s effects against chronic P. aeruginosa lung infection in animal models and its cytokine-modulating effects on leukocytes were investigated.

Synthesis and in vitro leishmanicidal activity of 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-substituted-1,3,4-thiadiazole derivatives.

A series of 2-(1-methyl-5-nitroimidazol-2-yl)-5-(1-piperazinyl, 1-piperidinyl and 1-morpholinyl)-1,3,4-thiadiazoles (3a-g) were synthesized and evaluated for in vitro leishmanicidal activity against Leishmania major promastigotes. The leishmanicidal data revealed that compounds 3a-g had strong and much better leishmanicidal activity than the reference drug pentostam. Compound 3c (piperazine analog) was the most active compound (IC50=0.

Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.

The inflammation in cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection is dominated by polymorphonuclear neutrophils (PMNs). There seems to be a relationship between the PMN-dominated inflammation, pronounced antibody production and a Th2-dominated response. Apart from mobilizing monocytes and PMNs from the bone marrow, GM-CSF, G-CSF and IL-3 select subsets of dendritic cells, which subsequently induce distinct Th responses.

Synthesis and in vitro leishmanicidal activity of 2-(5-nitro-2-furyl) and 2-(5-nitro-2-thienyl)-5-substituted-1,3,4-thiadiazoles.

A series of 2-(5-nitro-2-furyl) and 2-(5-nitro-2-thienyl)-5-substituted-1,3,4-thiadiazoles (5a-d and 6a-j) were synthesized and evaluated against Leishmania major promastigotes using (3)H-thymidine incorporation. Most of the compounds showed activity better than the reference drug sodium stibogluconate (Pentostam). The most active compound was 6c (IC(50)=0.

A quantitative study of epidermal Langerhans cells in cutaneous leishmaniasis caused by Leishmania tropica.

Objective: The purpose of this study was to characterize the number and distribution of epidermal Langerhans cells in different clinical forms of dry-type cutaneous leishmaniasis (CL).

Methods: Sixteen cases of dry-type cutaneous leishmaniasis caused by Leishmania tropica were studied. These cases were classified clinically as five cases of acute leishmaniasis with indurated papules, nodules and plaques with central crust formation and duration < 2 years, six cases of lupoid leishmaniasis with characteristic papules around previous scars of cutaneous leishmaniasis with duration > 2 years, and five cases of chronic nonlupoid type with nonhealing lesions of duration > 2 years.

Effect of smoking and abstention on oxidative burst and reactivity of neutrophils and monocytes.

Background: Smoking is associated with surgical wound infections, impaired wound healing, and tissue-destructive disorders. The mechanisms are largely unknown, but changes in the function and activity of inflammatory cells may be involved.

Methods: Seventy healthy volunteers (54 smokers and 16 never smokers) were included.

Ginseng modulates the immune response by induction of interleukin-12 production.

In infections with intracellular microorganisms such as mycobacteria and Leishmania parasites as well as certain extracellular chronic infections such as Pseudomonas aeruginosa a Th1 response with activation of macrophages is desirable. Several studies indicate that such a response is associated with better recovery from infection, improved course of the chronic infection, and higher survival rate. In Th1 responses there is increased interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) production, whereas that of interleukin-10 (IL-10) is decreased.

Cytokine modulating effect of ginseng treatment in a mouse model of Pseudomonas aeruginosa lung infection.

The major cause of morbidity and mortality in cystic fibrosis (CF) patients is chronic Pseudomonas aeruginosa lung infection. In a mouse model of P. aeruginosa lung infection mimicking that in CF patients, the effects of ginseng treatment on cytokine responses and the correlation between the changes in cytokine production and the lung pathology were studied.

Alginate production affects Pseudomonas aeruginosa biofilm development and architecture, but is not essential for biofilm formation.

Extracellular polymers can facilitate the non-specific attachment of bacteria to surfaces and hold together developing biofilms. This study was undertaken to qualitatively and quantitatively compare the architecture of biofilms produced by Pseudomonas aeruginosa strain PAO1 and its alginate-overproducing (mucA22) and alginate-defective (algD) variants in order to discern the role of alginate in biofilm formation. These strains, PAO1, Alg+ PAOmucA22 and Alg- PAOalgD, tagged with green fluorescent protein, were grown in a continuous flow cell system to characterize the developmental cycles of their biofilm formation using confocal laser scanning microscopy.

Pseudomonas aeruginosa alginate is refractory to Th1 immune response and impedes host immune clearance in a mouse model of acute lung infection.

Pseudomonas aeruginosa is an opportunistic respiratory pathogen that accounts for most of the morbidity and mortality in cystic fibrosis (CF) patients. In CF-affected lungs, the bacteria undergo conversion from a non-mucoid to a non-tractable mucoid phenotype, due to overproduction of alginate. The effect of alginate production on pathogenicity was investigated by using an acute lung infection mouse model that compared a non-mucoid P.

An antiinflammatory galactolipid from rose hip (Rosa canina) that inhibits chemotaxis of human peripheral blood neutrophils in vitro.

The galactolipid (2S)-1,2-di-O-[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3-O-beta-d-galactopyranosyl glycerol (1) isolated from dried and milled fruits of Rosa canina by bioassay-guided fractionation is an antiinflammatory agent with inhibitory effects on chemotaxis of human peripheral blood neutrophils in vitro. The inhibition of cell migration is not related to toxicity. The presence of 1 in rose hips may explain the clinically observed antiinflammatory properties of rose hip herbal remedies.

Antiplasmodial compounds from Cochlospermum tinctorium.

Fractionation of an ethanol extract of roots of Cochlospermum tinctorium afforded five compounds: 3-O-E-p-coumaroylalphitolic acid (1), cochloxanthin (2), dihydrocochloxanthin (3), alphitolic acid (4), and 1-hydroxytetradecan-3-one (5). This is the first example of a 1-hydroxyalkan-3-one obtained from plant material after gentle workup. The antiplasmodial activities of the compounds were determined, and the IC(50) value of 3-O-E-p-coumaroylalphitolic acid was 2.

Aurones interfere with Leishmania major mitochondrial fumarate reductase.

A series of aurones was analyzed for the ability to inhibit respiratory functions of mitochondria of Leishmania parasites. The aim of this study was to find a rational explanation for the activity of certain aurones and auronols as novel antiprotozoal compounds of plant origin. In a cell-free assay mitochondrial fumarate reductase from L.

Gerimax ginseng regulates both humoral and cellular immunity during chronic Pseudomonas aeruginosa lung infection.

Background: Chronic lung infection among patients with cystic fibrosis (CF), diffused panbronchiolitis, and chronic obstructive bronchiecteisis is often because of Pseudomonas aeruginosa. High morbidity and mortality in patients with CF are because of P. aeuruginosa that undergoes genotypic and phenotypic changes during prolonged stay in the lung resulting in increased antibiotic resistance, necessitating a search for alternative or supplement drugs.

In vitro antimycobacterial and antilegionella activity of licochalcone A from Chinese licorice roots.

Licochalcone A, extracted and purified from Chinese licorice roots, showed in vitro inhibitory effect on human pathogenic Mycobacteria species and Legionella species. M. tuberculosis, M.

Chalcones from Chinese liquorice inhibit proliferation of T cells and production of cytokines.

Licochalcone A (LicA), an oxygenated chalcone, has been shown to inhibit the growth of both parasites and bacteria. In this study, we investigated the effect of LicA and four synthetic analogues on the activity of human peripheral blood mononuclear cell proliferation and cytokine production. Four out of five chalcones tested inhibited the proliferation of lymphocytes measured by thymidine incorporation and by flow cytometry.

limonoids from Khaya senegalensis.

A new limonoid was isolated from the bark of Khaya senegalensis and identified as 2,6-dihydroxyfissinolide. The assignments of some signals in the (13)C NMR spectrum of fissinolide have been reversed and the signals of the (1)H NMR spectrum of methyl 3beta-acetoxy-6-hydroxy-1-oxomeliac-14-enoate have been assigned. The limonoids only showed moderate antiprotozoal activities.

Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung.

The leading cause of mortality in patients with cystic fibrosis (CF) is respiratory failure due in large part to chronic lung infection with Pseudomonas aeruginosa strains that undergo mucoid conversion, display a biofilm mode of growth in vivo and resist the infiltration of polymorphonuclear leukocytes (PMNs), which release free oxygen radicals such as H2O2. The mucoid phenotype among the strains infecting CF patients indicates overproduction of a linear polysaccharide called alginate. To mimic the inflammatory environment of the CF lung, P.