Anti-Inflammatory Effect of Fluvastatin on IL-8 Production Induced by Pseudomonas aeruginosa and Aspergillus fumigatus Antigens in Cystic Fibrosis

International audienceBACKGROUND: Early in life, patients with cystic fibrosis (CF) are infected with microorganisms including bacteria and fungi, particularly Pseudomonas aeruginosa and Aspergillus fumigatus. Since recent research has identified the anti-inflammatory properties of statins (besides their lipid-lowering effects), we investigated the effect of fluvastatin on the production of the potent neutrophil chemoattractant chemokine, IL-8, in whole blood from CF patients, stimulated by Pseudomonas aeruginosa (LPS) and Aspergillus fumigatus (AFA) antigens. RESULTS: Whole blood from adult patients with CF and from healthy volunteers was collected at the Rennes University Hospital (France). Blood was pretreated for 1 h with fluvastatin (0-300 µM) and incubated for 24 h with LPS (10 µg/mL) and/or AFA (diluted 1/200). IL-8 protein levels, quantified by ELISA, were increased in a concentration-dependent manner when cells were stimulated by LPS or AFA. Fluvastatin strongly decreased the levels of IL-8, in a concentration-dependent manner, in whole blood from CF patients. However, its inhibitory effect was decreased or absent in whole blood from healthy subjects. Furthermore, the inhibition induced by fluvastatin in CF whole blood was reversed in the presence of intermediates within the cholesterol biosynthesis pathway, mevalonate, farnesyl pyprophosphate or geranylgeranyl pyrophosphate that activate small GTPases by isoprenylation. CONCLUSIONS: For the first time, the inhibitory effects of fluvastatin on CF systemic inflammation may reveal the important therapeutic potential of statins in pathological conditions associated with the over-production of pro-inflammatory cytokines and chemokines as observed during the manifestation of CF. The anti-inflammatory effect could be related to the modulation of the prenylation of signalling proteins

The lactose operon from Lactobacillus casei is involved in the transport and metabolism of the human milk oligosaccharide core-2 N-acetyllactosamine

The lactose operon (lacTEGF) from Lactobacillus casei strain BL23 has been previously studied. The lacT gene codes for a transcriptional antiterminator, lacE and lacF for the lactose-specific phosphoenolpyruvate: phosphotransferase system (PTSLac) EIICB and EIIA domains, respectively, and lacG for the phospho-β-galactosidase. In this work, we have shown that L. casei is able to metabolize N-acetyllactosamine (LacNAc), a disaccharide present at human milk and intestinal mucosa. The mutant strains BL153 (lacE) and BL155 (lacF) were defective in LacNAc utilization, indicating that the EIICB and EIIA of the PTSLac are involved in the uptake of LacNAc in addition to lactose. Inactivation of lacG abolishes the growth of L. casei in both disaccharides and analysis of LacG activity showed a high selectivity toward phosphorylated compounds, suggesting that LacG is necessary for the hydrolysis of the intracellular phosphorylated lactose and LacNAc. L. casei (lacAB) strain deficient in galactose-6P isomerase showed a growth rate in lactose (0.0293 ± 0.0014 h-1) and in LacNAc (0.0307 ± 0.0009 h-1) significantly lower than the wild-type (0.1010 ± 0.0006 h-1 and 0.0522 ± 0.0005 h-1, respectively), indicating that their galactose moiety is catabolized through the tagatose-6P pathway. Transcriptional analysis showed induction levels of the lac genes ranged from 130 to 320-fold in LacNAc and from 100 to 200-fold in lactose, compared to cells growing in glucose

Primary intestinal lymphangiectasia (Waldmann's disease)

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur

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Taha Toros Arşivi, Dosya Adı: Nazım Hikmetİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Should the poultry red mite Dermanyssus gallinae be of wider concern for veterinary and medical science?

The poultry red mite Dermanyssus gallinae is best known as a threat to the laying-hen industry; adversely affecting production and hen health and welfare throughout the globe, both directly and through its role as a disease vector. Nevertheless, D. gallinae is being increasingly implemented in dermatological complaints in non-avian hosts, suggesting that its significance may extend beyond poultry. The main objective of the current work was to review the potential of D. gallinae as a wider veterinary and medical threat. Results demonstrated that, as an avian mite, D. gallinae is unsurprisingly an occasional pest of pet birds. However, research also supports that these mites will feed from a range of other animals including: cats, dogs, rodents, rabbits, horses and man. We conclude that although reported cases of D. gallinae infesting mammals are relatively rare, when coupled with the reported genetic plasticity of this species and evidence of permanent infestations on non-avian hosts, potential for host-expansion may exist. The impact of, and mechanisms and risk factors for such expansion are discussed, and suggestions for further work made. Given the potential severity of any level of host-expansion in D. gallinae, we conclude that further research should be urgently conducted to confirm the full extent of the threat posed by D. gallinae to (non-avian) veterinary and medical sectors

Diagnostic significance of Aspergillus species isolated from respiratory samples in an adult pneumology ward.

Although the diagnostic significance of isolating Aspergillus spp. from respiratory cultures has been studied in immunocompromised hosts with invasive pulmonary aspergillosis (IPA), little is known of such infections in immunocompetent patients with other forms of aspergillosis. In this study of adult pneumology ward patients, we examined the association between Aspergillus spp. and disease prevalence. Laboratory records from April 1998 to March 2009 were reviewed to identify patients with Aspergillus spp. in respiratory samples. Correlations between the isolated species and clinical characteristics of patients were evaluated. During the study period, 165 Aspergillus spp. isolates were detected in the respiratory cultures of 139 patients. Of these patients, 62 (45%) were colonized with Aspergillus spp. and displayed no clinical symptoms of aspergillosis, while 77 (55%) had a form of pulmonary aspergillosis, characterized as either chronic necrotizing pulmonary aspergillosis (CNPA) (48%), aspergilloma (29%), IPA (13%), or allergic bronchopulmonary aspergillosis (ABPA) (10%). The dominant species were Aspergillus fumigatus (41%), A. niger (32%), and A. versicolor (12%). A. fumigatus was most commonly isolated in patients with IPA, aspergilloma, and CNPA, whereas A. niger was the dominant species in colonized patients and those with ABPA. Isolation of an Aspergillus spp. from respiratory samples does not confirm it as the etiologic pathogen because airway colonization by Aspergillus spp. is a common feature in several chronic lung diseases. Repeated isolation of the identical Aspergillus species and detection of anti-Aspergillus antibodies and/or Aspergillus antigens in sera are needed to determine the isolate represents the etiologic agent of disease

Notes for genera: basal clades of Fungi (including Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota)

Compared to the higher fungi (Dikarya), taxonomic and evolutionary studies on the basal clades of fungi are fewer in number. Thus, the generic boundaries and higher ranks in the basal clades of fungi are poorly known. Recent DNA based taxonomic studies have provided reliable and accurate information. It is therefore necessary to compile all available information since basal clades genera lack updated checklists or outlines. Recently, Tedersoo et al. (MycoKeys 13:1--20, 2016) accepted Aphelidiomycota and Rozellomycota in Fungal clade. Thus, we regard both these phyla as members in Kingdom Fungi. We accept 16 phyla in basal clades viz. Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. Thus, 611 genera in 153 families, 43 orders and 18 classes are provided with details of classification, synonyms, life modes, distribution, recent literature and genomic data. Moreover, Catenariaceae Couch is proposed to be conserved, Cladochytriales Mozl.-Standr. is emended and the family Nephridiophagaceae is introduced

Lasiodiplodia theobromae deep mycosis in a kidney transplant patient

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