The Metacognitions about Binge Eating Questionnaire: Investigation of the association between specific metacognitions and Binge Eating Disorder.

Literature suggested that metacognitions are involved in eating problems and may be relevant to the understanding of Binge Eating Disorder (BED). The goal of the current studies was to develop the first self-report instrument on metacognitions about binge eating. In Study 1, a community sample completed the Metacognitions about Binge Eating Questionnaire (MBEQ); an Exploratory Factor Analysis (EFA) was performed. In study 2, a community sample completed the MBEQ and measures assessing severity of binge eating, irrational food beliefs, anxiety, depression, impulsiveness. A Confirmatory Factor Analysis (CFA) was performed. Concurrent and incremental validity were assessed. In study 3, a clinical sample of participants with a diagnosis of BED completed the MBEQ and other measures. Bivariate correlational analysis and hierarchical linear regression were performed. Participants from the general population and participants with a diagnosis of BED were compared. EFA and CFA supported a two-factor solution consisting of positive and negative metacognitions about binge eating. Concurrent and incremental validity were acceptable. The metacognitions factors correlated positively with anxiety, depression, irrational food beliefs, impulsiveness in the community sample, and anxiety, irrational food beliefs, impulsiveness in clinical sample. The metacognitions factors contributed to the prediction of BEDs symptoms, in community and clinical samples, over and above age, gender, impulsiveness, anxiety, depression, irrational food beliefs. The MBEQ possesses good psychometric properties and appears a reliable and valid measure of positive and negative metacognitions about binge eating. Metacognitions about binge eating could be a therapeutic target to reduce the severity of binge eating episodes.

Prevalence and 6-month recovery of olfactory dysfunction: a multicentre study of 1363 COVID-19 patients.

OBJECTIVE: To investigate prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients according to the disease severity. METHODS: From 22 March to 3 June 2020, 2581 COVID-19 patients were identified from 18 European hospitals. Epidemiological and clinical data were extracted at baseline and within the 2-month post-infection. RESULTS: The prevalence of OD was significantly higher in mild form (85.9%) compared with moderate-to-critical forms (4.5-6.9%; P = 0.001). Of the 1916 patients with OD, 1363 completed the evaluations (71.1%). A total of 328 patients (24.1%) did not subjectively recover olfaction 60 days after the onset of the dysfunction. The mean duration of self-reported OD was 21.6 ± 17.9 days. Objective olfactory evaluations identified hyposmia/anosmia in 54.7% and 36.6% of mild and moderate-to-critical forms, respectively (P = 0.001). At 60 days and 6 months, 15.3% and 4.7% of anosmic/hyposmic patients did not objectively recover olfaction, respectively. The higher baseline severity of objective olfactory evaluations was strongly predictive of persistent OD (P < 0.001). CONCLUSION: OD is more prevalent in mild COVID-19 forms than in moderate-to-critical forms. OD disappeared in 95% of patients regarding objective olfactory evaluations at 6 months.

Recent trends in primary-care antidepressant prescribing to children and young people: an e-cohort study.

BACKGROUND: Concerns relating to increased use of psychotropic medication contrast with those of under-treatment and under-recognition of common mental disorders in children and young people (CYP) across developed countries. Little is known about the indications recorded for antidepressant prescribing in primary care in CYP. METHOD: This was an electronic cohort study of routinely collected primary-care data from a population of 1.9 million, Wales, UK. Poisson regression was undertaken to model adjusted counts of recorded depression symptoms, diagnoses and antidepressant prescriptions. Associated indications were explored. RESULTS: 3 58 383 registered patients aged 6-18 years between 1 January 2003 and 31 December 2013 provided a total of 19 20 338 person-years of follow-up. The adjusted incidence of antidepressant prescribing increased significantly [incidence rate ratio (IRR) for 2013 = 1.28], mainly in older adolescents. The majority of new antidepressant prescriptions were for citalopram. Recorded depression diagnoses showed a steady decline (IRR = 0.72) while depression symptoms (IRR = 2.41) increased. Just over half of new antidepressant prescriptions were associated with depression (diagnosis or symptoms). Other antidepressant prescribing, largely unlicensed, was associated with diagnoses such as anxiety and pain. CONCLUSION: Antidepressant prescribing is increasing in CYP while recorded depression diagnoses decline. Unlicensed citalopram prescribing occurs outside current guidelines, despite its known toxicity in overdose. Unlicensed antidepressant prescribing is associated with a wide range of diagnoses, and while accepted practice, is often not supported by safety and efficacy studies. New strategies to implement current guidance for the management of depression in CYP are required.

De novo transcriptome assembly for a non-model species, the blood-sucking bug Triatoma brasiliensis, a vector of Chagas disease.

High throughput sequencing (HTS) provides new research opportunities for work on non-model organisms, such as differential expression studies between populations exposed to different environmental conditions. However, such transcriptomic studies first require the production of a reference assembly. The choice of sampling procedure, sequencing strategy and assembly workflow is crucial. To develop a reliable reference transcriptome for Triatoma brasiliensis, the major Chagas disease vector in Northeastern Brazil, different de novo assembly protocols were generated using various datasets and software. Both 454 and Illumina sequencing technologies were applied on RNA extracted from antennae and mouthparts from single or pooled individuals. The 454 library yielded 278 Mb. Fifteen Illumina libraries were constructed and yielded nearly 360 million RNA-seq single reads and 46 million RNA-seq paired-end reads for nearly 45 Gb. For the 454 reads, we used three assemblers, Newbler, CAP3 and/or MIRA and for the Illumina reads, the Trinity assembler. Ten assembly workflows were compared using these programs separately or in combination. To compare the assemblies obtained, quantitative and qualitative criteria were used, including contig length, N50, contig number and the percentage of chimeric contigs. Completeness of the assemblies was estimated using the CEGMA pipeline. The best assembly (57,657 contigs, completeness of 80 %, <1 % chimeric contigs) was a hybrid assembly leading to recommend the use of (1) a single individual with large representation of biological tissues, (2) merging both long reads and short paired-end Illumina reads, (3) several assemblers in order to combine the specific advantages of each.

Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia.

Because of its ability to efficiently inhibit in vitro cytokine production by activated macrophages, we hypothesized that interleukin (IL) 10 might be of particular interest in preventing endotoxin-induced toxicity. We therefore examined the effects of IL-10 administration before lipopolysaccharide (LPS) challenge in mice. A marked reduction in the amounts of LPS-induced tumor necrosis factor (TNF) release in the circulation was observed after IL-10 pretreatment at doses at low as 10 U. IL-10 also efficiently prevented the hypothermia generated by the injection of 100 micrograms LPS. Finally, pretreatment with a single injection of 1,000 U IL-10 completely prevented the mortality consecutive to the challenge with 500 micrograms LPS, a dose that was lethal in 50% of the control mice. We conclude that IL-10 inhibits in vivo TNF secretion and protects against the lethality of endotoxin in a murine model of septic shock.

A dynamic model of nutrient uptake by root hairs.

Root hairs are known to be important in the uptake of sparingly soluble nutrients by plants, but quantitative understanding of their role in this is weak. This limits, for example, the breeding of more nutrient-efficient crop genotypes. We developed a mathematical model of nutrient transport and uptake in the root hair zone of single roots growing in soil or solution culture. Accounting for root hair geometry explicitly, we derived effective equations for the cumulative effect of root hair surfaces on uptake using the method of homogenization. Analysis of the model shows that, depending on the morphological and physiological properties of the root hairs, one of three different effective models applies. They describe situations where: (1) a concentration gradient dynamically develops within the root hair zone; (2) the effect of root hair uptake is negligibly small; or (3) phosphate in the root hair zone is taken up instantaneously. Furthermore, we show that the influence of root hairs on rates of phosphate uptake is one order of magnitude greater in soil than solution culture. The model provides a basis for quantifying the importance of root hair morphological and physiological properties in overall uptake, in order to design and interpret experiments in different circumstances.

[A clinical case of spontaneous involution of systemic cat scratch disease]. / Involution spontanée d'une forme systémique de maladie par griffade de chat: à propos d'un cas.

Typical Cat-scratch disease (CSD) manifests as regional lymphadenopathy following cat scratch and sometimes associated with mild fever. There is a lot of atypical manifestations and some of those have systemic involvement. Hepatosplenic CSD is a systemic presentation associating fever of unknown origin with nodules in the liver and/or the spleen. Ultrasound abdominal examination shows nodules (3-30 mm) in the spleen and/or in the liver. Diagnostic is based on serology for B henselae (always IgG + and sometimes IgM +), or polymerase chain reaction (PCR) on the liver to test for the presence of B henselae. Hepatosplenic CSD is rare and therefore underdiagnosed. There is no consensus about the treatment but most of the authors suggest to treat with rifampicine. We report a case of a 4-years-old girl presenting with fever of unknown origin (FUO), high inflammatory markers with normal leukocytosis and hepatosplenic nodules. The diagnosis of CSD was made retrospectively. Evolution was favourable even though no specific antibiotic treatment for Bartonella henselae was administrated.

Arabidopsis AUX1 gene: a permease-like regulator of root gravitropism.

The plant hormone auxin regulates various developmental processes including root formation, vascular development, and gravitropism. Mutations within the AUX1 gene confer an auxin-resistant root growth phenotype and abolish root gravitropic curvature. Polypeptide sequence similarity to amino acid permeases suggests that AUX1 mediates the transport of an amino acid-like signaling molecule. Indole-3-acetic acid, the major form of auxin in higher plants, is structurally similar to tryptophan and is a likely substrate for the AUX1 gene product. The cloned AUX1 gene can restore the auxin-responsiveness of transgenic aux1 roots. Spatially, AUX1 is expressed in root apical tissues that regulate root gravitropic curvature.

Comparing de novo and reference-based transcriptome assembly strategies by applying them to the blood-sucking bug Rhodnius prolixus.

High Throughput Sequencing capabilities have made the process of assembling a transcriptome easier, whether or not there is a reference genome. But the quality of a transcriptome assembly must be good enough to capture the most comprehensive catalog of transcripts and their variations, and to carry out further experiments on transcriptomics. There is currently no consensus on which of the many sequencing technologies and assembly tools are the most effective. Many non-model organisms lack a reference genome to guide the transcriptome assembly. One question, therefore, is whether or not a reference-based genome assembly gives better results than de novo assembly. The blood-sucking insect Rhodnius prolixus-a vector for Chagas disease-has a reference genome. It is therefore a good model on which to compare reference-based and de novo transcriptome assemblies. In this study, we compared de novo and reference-based genome assembly strategies using three datasets (454, Illumina, 454 combined with Illumina) and various assembly software. We developed criteria to compare the resulting assemblies: the size distribution and number of transcripts, the proportion of potentially chimeric transcripts, how complete the assembly was (completeness evaluated both through CEGMA software and R. prolixus proteome fraction retrieved). Moreover, we looked for the presence of two chemosensory gene families (Odorant-Binding Proteins and Chemosensory Proteins) to validate the assembly quality. The reference-based assemblies after genome annotation were clearly better than those generated using de novo strategies alone. Reference-based strategies revealed new transcripts, including new isoforms unpredicted by automatic genome annotation. However, a combination of both de novo and reference-based strategies gave the best result, and allowed us to assemble fragmented transcripts.

The action of pokeweed antiviral protein and ricin A-chain on mutants in the alpha-sarcin loop of Escherichia coli 23S ribosomal RNA.

The alpha-sarcin loop of Escherichia coli 23S rRNA is a universally-conserved structure involved in the binding of elongation factors Tu and G and is the site of action of the ribosome-inactivating proteins (RIPs). One such group, the N-glycosidase RIPs, act by the removal of a single adenine residue (A2660) believed to exist in a GAGA-containing tetraloop structure. The action of two RIPs, the catalytic A-chain from the heterodimeric toxic lectin ricin (RTA) and the single-chain RIP pokeweed antiviral protein (PAP), which are known to be highly homologous in tertiary structure, was determined on native ribosomes or naked 23S rRNA containing mutations designed to affect the structure of the GAGA tetraloop. One such mutant rRNA containing G2663C, which abolishes the potential tetraloop by disrupting the Watson-Crick base-pair involved in closing it, resulted in a loss of depurination by RTA, but not by PAP. A similar result was observed for mutant G2661A. The double mutant C2658G + G2663C, which restores the tetraloop-closing base-pair but in the reverse orientation, resulted in sensitivity to both PAP and RTA, as in the wild-type. Thus, the tetraloop structure is required for the action of RTA, but not of PAP, and unlike RTA, PAP does not require G at position 2661. RNA containing the G2664C mutation, which lies outside the tetraloop, served as a substrate for both PAP and RTA. The comparison of the recognition elements for PAP and RTA was made with naked (deproteinised) rRNA, because RTA does not act on E. coli ribosomes. However, PAP is active on E. coli ribosomes, and it was found that the action of PAP on ribosomes containing the above mutations paralleled exactly that on the corresponding naked rRNAs. It is concluded that the recognition elements for PAP and RTA differ and may account, at least in part, for the fact that PAP but not RTA catalyses the depurination of E. coli ribosomes.

Recent trends in the incidence of anxiety and prescription of anxiolytics and hypnotics in children and young people: An e-cohort study.

BACKGROUND: Little is known regarding the recognition of anxiety in children and young people (CYP) in primary care. This study examined trends in the presentation, recognition and recording of anxiety and of anxiolytic and hypnotic prescriptions for CYP in primary care. METHOD: A population-based retrospective electronic cohort of individuals aged 6-18 years between 2003 and 2011 within the Secure Anonymised Information Linkage (SAIL) Databank primary care database was created. Incidence rates were calculated using person years at risk (PYAR) as a denominator accounting for deprivation, age and gender. RESULTS: We identified a cohort of 311,343 registered individuals providing a total of 1,546,489 person years of follow up. The incidence of anxiety symptoms more than tripled over the study period (Incidence Rate Ratio (IRR)=3.55, 95% CI 2.65-4.77) whilst that of diagnosis has remained stable. Anxiolytic/hypnotic prescriptions for the cohort as a whole did not change significantly over time; however there was a significant increase in anxiolytic prescriptions for the 15-18 year age group (IRR 1.62, 95% CI 1.30-2.02). LIMITATIONS: There was a lack of reliable information regarding other interventions available or received at a primary, secondary or tertiary level such as psychological treatments. CONCLUSIONS: There appears to be a preference over time for the recording of general symptoms over diagnosis for anxiety in CYP. The increase in anxiolytic prescriptions for 15-18 year olds is discrepant with current prescribing guidelines. Specific guidance is required for the assessment and management of CYP presenting with anxiety to primary care, particularly older adolescents.

Characterisation of monoclonal antibodies against human interleukin-10 and their use in an ELISA for the measurement of this cytokine.

Biological and biochemical characteristics of monoclonal antibodies (MABs) raised against human interleukin-10 (IL-10) are described as well as their use in the design of a specific ELISA for the measurement of the cytokine. 21 murine anti-human interleukin-10 (IL-10) MABs were obtained by fusion of splenocytes from mice immunized against human recombinant IL-10 with SP2/0 myelomatous cells. These antibodies define three major antigenic areas on the IL-10 molecule, one of which comprises epitopes involved in receptor binding and induction of biological activity. They recognize recombinant human IL-10 with affinities ranging from 1.3 x 10(-7) to 3 x 10(-11), as well as natural IL-10. Most of them also recognize viral IL-10 (vIL-10) encoded by the Epstein-Barr virus (EBV). A specific human-IL-10 ELISA has been developed using two MABs (18 and 19) as capture antibody and one MAB (17) as detector. The sensitivity (3 pg/ml), precision (intra-assays < 4%), reproducibility (interassay < 3%), and accuracy (recoveries, ranging between 84 and 107%, in several fluids) of the assay, plus its excellent performance in dilution tests, and the lack of interference when in the presence of possible cross-reactive substances, permits accurate cytokine measurement in biological fluids such as serum, plasma, bronchoalveolar lavage, urine and culture supernatants. Using the assay, IL-10 was measurable in the plasma of patients with septic shock (range 11-2740 pg/ml) whereas IL-10 plasma levels were < 7.8 pg/ml in healthy volunteers.

The toll-like receptor 4 Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia.

SETTING: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide. Studies in a murine model of pulmonary TB have identified a role for Toll-like receptor 4 (TLR4) in the development of chronic lung infection with Mycobacterium tuberculosis. The Asp299Gly polymorphism in the human TLR4 gene is associated with in vivo hyporesponsiveness to lipopolysaccharide (LPS) in Caucasians. OBJECTIVE: To determine whether TLR4 Asp299Gly influences LPS responses or susceptibility to pulmonary TB in humans in a Gambian population sample. DESIGN: We compared whole blood monokine responses to LPS in 245 healthy blood donors stratified by TLR4 Asp299Gly genotype to assess whether this polymorphism was functional in this population. A case-control study of 640 subjects was conducted to investigate whether TLR4 Asp299Gly was associated with TB. RESULTS: LPS-induced tumour necrosis factor, interleukin-1 beta and interleukin-10 production was not influenced by TLR4 Asp299Gly genotype. There was no association between TLR4 Asp299Gly and TB. CONCLUSION: Our data suggest that TLR4 Asp299Gly has no influence on monocyte LPS responses or susceptibility to TB in Gambians and could be an ancient neutral polymorphism.

Effects of serotonin on coronary arteries of cardiac transplant recipients.

Serotonin constricts coronary arteries with endothelial dysfunction. To detect early graft artery disease, the responses to intracoronary serotonin were studied 1 month (group A, 14 patients) and 1 year (group B, 13 patients) after orthotopic cardiac transplantation. No patient had evidence of rejection and all had angiographically normal coronary arteries. Serotonin in increasing doses (1, 10 and 20 micrograms/min for 2.5 minutes each) was infused into the coronary circulation. Diameters of proximal, middle and distal segments were measured by quantitative angiography. At the maximal concentration of serotonin, the diameters of the proximal segments decreased to 73 +/- 4% (percentage of the baseline) in group A; the diameters of the middle and distal segments decreased to 67 +/- 5 and 63 +/- 4%, whereas in group B, the diameters of the proximal, middle and distal segments were 90 +/- 6% (p < 0.02 vs group A value), 88 +/- 5% (p < 0.01 vs group A value) and 84 +/- 4% (p < 0.01 vs group A value), respectively. These changes were significantly (p < 0.02) different from those observed in 6 control patients in whom no constriction was induced by intracoronary serotonin. Moreover, coronary plasma endothelin levels were significantly higher in group A than in group B and control patients (5.6 +/- 0.3 vs 4.3 +/- 0.2 fmol/ml in group B and 3.9 +/- 0.3 fmol/ml in control patients). Thus, an abnormal response to intracoronary serotonin seems to occur often in transplant patients, and this abnormality is unexpectedly more pronounced in the early weeks after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Human cytokine responses to cardiac transplantation and coronary artery bypass grafting.

Cardiac surgery with cardiopulmonary bypass triggers an inflammatory response involving proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interleukin-8. To elucidate the pathophysiology of this cytokine response, we explored the possible differences in cytokine responses between patients undergoing heart transplantation and those undergoing coronary artery bypass grafting. Plasma levels of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured in eight patients undergoing heart transplantation (mean age 44 years) and eight patients undergoing coronary artery bypass grafting (mean age 61 years). Duration of cardiopulmonary bypass and ischemic time were both longer in the heart transplantation group than in the coronary artery bypass grafting group (133 +/- 26 min vs 100 +/- 31 min, p < 0.05, and 130 +/- 47 min vs 58 +/- 21 min, p < 0.005, respectively). Samples were collected before heparin administration, at aortic crossclamping and declamping, and at 0.5, 1, 1.5, 2, 4, 12, and 24 hours after declamping. Tumor necrosis factor-alpha levels were significantly higher 30 minutes after aortic declamping in the heart transplantation group than in the coronary artery bypass grafting group (68 +/- 30 vs 18 +/- 5 pg/ml, p < 0.05). Interleukin-6 and interleukin-8 levels were also significantly higher 90 minutes after declamping in patients undergoing heart transplantation than in those undergoing coronary artery bypass grafting (310 +/- 63 vs 169 +/- 24 pg/ml, p < 0.05, and 73 +/- 17 vs 24 +/- 5 pg/ml, p < 0.01, respectively). Furthermore, interleukin-6 and interleukin-8 values 90 minutes after declamping were significantly correlated with the ischemic time (r = 0.72 and r = 0.82, respectively, both p < 0.05). Interleukin-10 levels in both groups rose to reach a peak value of around 115 pg/ml 1 hour after declamping. Patients undergoing heart transplantation exhibited a second peak of tumor necrosis factor-alpha, interleukin-8, and interleukin-10 levels 12 hours after declamping, probably related to the administration of rabbit antihuman thymocyte immunoglobulin (Thymoglobuline) 3 hours after declamping. Interleukin-6 levels decreased more significantly 12 and 24 hours after declamping in patients undergoing heart transplantation, probably related to methylprednisolone therapy. In conclusion, cardiopulmonary bypass is associated with the production of both proinflammatory and antiinflammatory cytokines. The production of proinflammatory cytokines in patients undergoing heart transplantation is higher than that in patients undergoing coronary artery bypass grafting, and this increase could be related to the longer duration of ischemia in the former group. The later course of cytokine levels after heart transplantation may be further influenced by immunosuppressive therapy.

Defective translation of tumor necrosis factor mRNA in lipopolysaccharide-tolerant macrophages.

Macrophage activation by lipopolysaccharide (LPS) results in the translational activation of tumor necrosis factor (TNF) mRNA. The initial phase of macrophage activation is followed by a refractory state called LPS tolerance characterized by an impaired TNF production in response to a secondary LPS challenge. LPS-tolerant macrophages contain high amounts of TNF mRNA, suggesting a translational regulation of TNF biosynthesis. The induction of LPS tolerance was studied in RAW 264.7 macrophages stably transfected with a chloramphenicol acetyl-transferase (CAT) reporter gene construct driven by a constitutive cytomegalovirus promoter and containing the 3' untranslated region of the murine TNF gene. We found that primary stimulation of transfected cells by LPS (1 ng/ml, 12 hr) resulted in a marked suppression (80%) of CAT accumulation in response to a secondary LPS challenge (1 microgram/ml, 6 hr). In contrast, the accumulation of CAT mRNA was not influenced by LPS tolerance. Using the same CAT reporter, we observed that the serine/threonine phosphatases 1 and 2A inhibitor okadaic acid induced TNF mRNA translation and that this activation was not inhibited by LPS-tolerance. In conclusion, these data indicate that deficient production of TNF in LPS-tolerant macrophages in response to a second LPS challenge is characterized by a defective translation of TNF mRNA. However, this hyporesponsiveness to LPS is specific, since translation of TNF mRNA induced by okadaic acid is not inhibited in LPS-tolerant macrophages.

Blood interleukin 10 levels parallel the severity of septic shock.

PURPOSE: The aim of this study was to investigate the relation between interleukin (IL) 10, tumor necrosis factor alpha (TNF alpha), IL-1, and IL-6 levels in patients with septic shock and relate these cytokine levels to the development of organ failure. PATIENTS AND METHODS: In 11 patients with septic shock of recent onset, blood was sampled for determinations of TNF, IL-1, IL-6, and IL-10. The degree of organ failure was scored for four organ systems (respiratory, hepatic, renal, hematologic) in the first 48 hours of the study. RESULTS: The APACHE II score was 21 +/- 4. Three patients died. IL-10 levels were directly correlated with TNF levels (r = 0.73, P < .05) and IL-6 levels (r = 0.67, P < .05); and inversely correlated with total C3 (r = -0.73, P < .05) and CH50 (r = -0.68, P < .05). Both IL-10 and TNF levels were correlated to the organ failure score (r = 0.75 and r = 0.68, both P < .01). Six patients with high IL-10 levels (> 60 pg/mL) had lower C3 (37 +/- 11 v 62 +/- 10 mg/dL) and CH50 (32 +/- 7 v 68 +/- 19%), and higher organ failure scores (5.7 +/- 0.8 v 3.8 +/- 1.3) than those with low IL-10 levels (all P < .05). CONCLUSION: Although IL-10 has an inhibitory effect on the production of cytokines, it is released together with TNF and IL-6 in patients with septic shock. IL-10 blood levels are directly related to the severity of inflammation and the development of organ failure in septic shock.

Efficacy of oral immunotherapy on respiratory infections in hemodialysis patients: a double-blind, placebo-controlled study.

BACKGROUND: Hemodialysis (HD) patients suffer from several immune defects that make them prone to develop bacterial infections, in particular respiratory tract infections (RTIs). PATIENTS AND METHODS: As previous studies have shown that oral immunotherapy with an immunomodulating bacterial extract (IBE) is effective against RTIs, we decided to test its efficacy and safety in HD patients during a double-blind placebo-controlled prospective study. 40 HD patients with a documented history of RTIs in the previous year were treated for 24 weeks of the endemic season with one capsule daily of IBE (n = 21) or placebo (PL, n = 19). Clinical examinations, measurements of Mac-1 and gp150.95 on circulating phagocytes and routine laboratory evaluations were performed at week 0, 4, 12 and 24. Patients were also examined at each dialysis session allowing an accurate recording of any infectious episode, its treatment and of any untoward effect. RESULTS: During the last period of the study (weeks 13-24), IBE significantly reduced the number of patients with RTIs and consequently of antibiotic treatment courses as compared to PL (p = 0.018), whereas no difference was detected between IBE and PL during periods I (weeks 0-4) and II (weeks 5-12). There was no difference between IBE and PL for other, non respiratory infections. IBE was associated at several time points with an increased expression on phagocytes of adhesion molecules involved in phagocytosis (Mac-1 and gp150.95). However, the expression of these molecules was not predictive for the occurrence of RTI. IBE was on the whole as well tolerated as PL, 7 patients presented side effects (5 IBE, 2 PL, NS) which led to drop-out in 4 cases (3 IBE, 1 PL). No serious side effect was recorded, gastrointestinal upset being the most prevalent type. CONCLUSION: The results of this study indicate that immunomodulation with selected bacterial extracts constitutes a promising approach for the prevention of bacterial airway infections in groups at risk, such as HD patients.

Production, partial characterization, and potential diagnostic use of salicylate hydroxylase from Pseudomonas putida UUC-1.

An unusual strain of Pseudomonas putida UUC-1 capable of growth at high salicylate concentration (10 gl-1) was investigated with the aim of developing an assay and a biosensor system for determining salicylate in body fluids by utilizing the salicylate hydroxylase enzyme. Medium and growth condition optimization were carried out under chemostat conditions. The highest biomass yield was at 4.0 gl-1 salicylate, 25 degrees C, pH 6.5, and 0.2 h-1 dilution rate. Growth occurred at up to 0.45 h-1 dilution rate, producing 236 Ul-1 enzyme activity and an output of 424 U h-1. The activity and productivity were higher than any reported in the literature for this enzyme. It had a Km value of 2.07 +/- 0.32 microM and an M(r) of approximately 43,000. In addition, its specific activity in the crude extract (0.8-0.9 U mg-1 protein) was similar to the commercially available enzyme. No plasmid DNA was detected in this strain, and no salicylate-negative isolates were obtained when curing with mitomycin C. It is therefore proposed that our strain has a chromosomally located inducible salicylate hydroxylase gene that enables it to grow at high salicylate. This strain also offers a means of cheaply producing large quantities of the enzyme through standard fermentation techniques.

[Role of interleukin-10 in the regulation of immune responses in infectious diseases]. / Rôle de l'interleukine-10 dans la régulation des résponses immunes en pathologie infectieuse.

Interleukin-10 (IL-10) is a new anti-inflammatory and immunosuppressive cytokine produced in the course of several experimental and clinical infections. In this paper, we review the major properties of IL-10 in vitro and we discuss the role of endogenous IL-10 in the pathogenesis of infectious diseases.