[A disseminated strongyloidiasis in a non immunocompromised patient]. / Une strongyloïdose disséminée chez un patient immunocompétent.

Strongyloidiasis is a parasitosis mainly located in tropical and subtropical regions. Its European incidence is increasing due to population migration. The symptomatology is variable, largely depending on the host immune status. The diagnosis may be challenging as a specific inquiry is needed. The disseminated status, called hyperinfection syndrome, is a life-threatening disease that might occur in immunosuppressed patients. The patient's chances for a successful outcome depend on a quick and specific management. The treatment is based on anthelminthic agents such as ivermectine or albendazole for which the dosage will vary according to the infection type.

La strongyloïdose ou anguillulose est une parasitose principalement retrouvée dans les régions tropicales ou subtropicales. Son incidence en Europe est en augmentation suite aux flux migratoires. Sa symptomatologie est très variable et dépend fortement du statut immunitaire de l'hôte. Le diagnostic peut être difficile et nécessite une recherche spécifique. La forme disséminée, appelée hyperinfection, est typiquement présente chez les patients immunodéprimés. Elle est mortelle, surtout en l'absence de prise en charge adéquate. Le traitement est basé sur les antihelminthiques tels que l'ivermectine et l'albendazole dont la posologie est à adapter en fonction du type d'infection.

Unravelling the mechanisms of a protein refolding process based on the association of detergents and co-solvents.

A new technique associating the detergent Sodium Dodecyl Sulphate (SDS) and an alcohol-type co-solvent has been set up, showing an unexpected efficiency to refold several types of soluble or membrane proteins. The present contribution deepens the fundamental knowledge on the phenomena underlying this process, considering the refolding of two model peptides featuring the main protein secondary structures: α-helix and ß-sheet. Their refolding was monitored by fluorescence and circular dichroism, and it turns out that: (i) 100% recovery of the folded structure is observed for both peptides, (ii) the highest the SDS concentration, the more co-solvent to be added to recover the peptides' native structures, (iii) a high alcohol concentration is required to alter the SDS denaturing properties, (iv) the co-solvent performance relies on its specific lipophilic-hydrophilic balanced character, (v) the size of the micelle formed by the detergent does not enter the process critical parameters, and (vi) increasing the salt concentration up to 1 M NaCl has a beneficial impact on the process efficiency. These mechanistic aspects will help us to improve the method and extend its application. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Cloning and functional characterization of Δ6 fatty acid desaturase (FADS2) in Eurasian perch (Perca fluviatilis).

The Eurasian perch (Perca fluviatilis) is a freshwater carnivorous species of high interest to diversify inland aquaculture. However, little is known about its ability to bioconvert polyunsaturated fatty acids (PUFAs) from plant oils into long chain polyunsaturated fatty acids (LC-PUFAs). In this study, special attention has been given to the fatty acid desaturase 2 (FADS2) which is commonly described to be a rate-limiting enzyme of the LC-PUFA biosynthesis. This work reports on the cloning, tissue expression and functional characterization of the Eurasian perch fads2, but also on the cloning of two alternative splicing transcripts named fads2-AS1 and fads2-AS2. The fads2 cDNA cloned is composed of an open reading frame (ORF) of 1338 nucleotides (nt) and encodes a protein of 445 amino acids. This deduced amino acid sequence displays the typical structure of microsomal FADS2 including two transmembrane domains and an N-terminal cytochrome b5 domain with the "HPGG" motif. Quantitative real-time PCR assay of fads2, fads2-AS1 and fads2-AS2 expressions revealed that the fads2 transcript was mainly expressed in the liver and intestine and exhibited a typical gene expression pattern of freshwater species while fads2-AS1 and fads2-AS2 genes were highly expressed in the brain, followed by the liver and intestine. Functional characterization of Eurasian perch FADS2 in transgenic yeast showed a fully functional Δ6 desaturation activity toward C18 PUFA substrates, without residual Δ5 and Δ8 desaturase activities.

First isolation of a rabid bat infected with European bat lyssavirus in Luxembourg.

Rabid bats are regularly reported in Europe, especially in countries that have implemented a bat surveillance network. In May 2013, bat rabies was evidenced for the first time in Luxembourg (southern city of Differdange). The rabies virus, an EBLV-1b strain, was diagnosed in a serotine bat that bit a 29-year-old male person while he was asleep. The man received rapidly a post-exposure RABV treatment and was put under strict medical supervision.

Effect of physiological determinants and cardiac disease on plasma adiponectin concentrations in dogs.

BACKGROUND: In humans, a high concentration of adiponectin is associated with a favorable cardiovascular risk profile whereas, in patients with heart failure (HF), a high concentration of adiponectin is associated with a less favorable prognosis. HYPOTHESIS/OBJECTIVES: To evaluate the physiological determinants of plasma adiponectin concentration in dogs and the influence of heart disease, myxomatous mitral valve disease (MMVD), and dilated cardiomyopathy (DCM). ANIMALS: One hundred and fourteen client-owned dogs and 9 Beagles from the research colony of the Clinical Veterinary Unit of the University of Liège. METHODS: We prospectively measured circulating adiponectin concentration in healthy control dogs (n = 77), dogs with MMVD (n = 22) and dogs with DCM (n = 15) of various degrees of severity. Diagnosis was confirmed by Doppler echocardiography. Plasma adiponectin concentration was measured by a canine-specific sandwich ELISA kit. RESULTS: An analysis of covariance showed an association between adiponectin concentration and age, neuter status, and heart disease. No association between adiponectin concentration and class of HF, sex, body condition score, body weight, circadian rhythm, or feeding was found. Plasma adiponectin concentration was negatively correlated with age (P = .001). Adiponectin was lower in neutered (P = .008) compared to intact dogs. Circulating adiponectin concentration was increased in dogs with DCM compared to healthy dogs (P = .018) and to dogs with MMVD (P = .014). CONCLUSIONS AND CLINICAL IMPORTANCE: Age and neutering negatively influence circulating adiponectin concentration. Plasma adiponectin concentration increased in dogs with DCM. Additional research is required to investigate if this hormone is implicated in the pathophysiology of DCM and associated with clinical outcome.

Febrile ulceronecrotic Mucha-Habermann disease.

The Mucha-Habermann disease is an inflammatory disease of the skin and is a variant of pityriasis lichenoides et varioliformis acuta. We describe the case of a 64-years-old woman who was admitted for erysipelas of the face. Despite treatment, evolution was marked by the appearance of a necrotising ulcerative area in the centre of the erysipelas associated with local oedema and headache. A skin biopsy revealed a pityriasis lichenoides et varioliformis acuta. Corticosteroids led to a rapid stabilisation of lesions, and after 6 months the patient shows only a small area of frontal hypopigmentation. The aetiology remains uncertain. There is no established standard treatment. We would like to draw attention of the medical and surgical specialists to this rare disease. The diagnosis should be considered in a necrotic lesion associated with rapid expansion of systemic and peripheral cutaneous signs. Diagnosis must be considered to avoid unnecessary debridement and extensive scars.

[Thrombotic thrombocytopenic purpura associated with interferon therapy in a HIV and HCV co-infected woman]. / Purpura thrombotique thrombocytopénique induit par l'interféron chez une femme co-infectée par le VIH et le VHC.

INTRODUCTION: Causes of acquired thrombotic thrombocytopenic purpura (TTP) are multiple and rarely iatrogenic. CASE REPORT: A 40-year-old, HIV and hepatitis C virus co-infected woman was treated with interferon and ribavirine and developed a TTP confirmed by the presence of anti-ADAMTS 13 antibodies. The outcome was favourable when treatment was discontinued and rituximab infusion administered. CONCLUSION: The occurrence of anemia and thrombocytopenia in patients treated with interferon and ribavirine is not always related to direct toxicities of these treatments. The ADAMS 13 testing may help the clinician to diagnose iatrogenic acquired TTP.

[Paradoxical reactions induced by antituberculous drugs in non-HIV infected patients: a cases series of four patients and literature review]. / Réactions paradoxales sous traitement antituberculeux chez des personnes non infectées par le VIH : quatre nouvelles observations et revue de la littérature.

INTRODUCTION: The features of paradoxical reactions (PR) that occurred in non-HIV infected patients treated with antituberculous drugs are diverse. We report four new cases of such PR and review the literature. PATIENTS AND METHODS: Were included all consecutive patients with PR that occurred in non-HIV infected patients who were treated for tuberculosis and followed-up in the department of internal medicine and infectious diseases between January 1st, 2009 and July 31st, 2010. RESULTS: Three of the patients were male. Their median age was 28.5 years. Tuberculous locations were pulmonary (two instances) and extrapulmonary (three instances). Paradoxical reactions occurred after a median of 5.5 weeks after initiation of antituberculous treatment. The PR presented as hypercalcemia (n=1), spondylitis of the 9th thoracic vertebra (n=1), intracerebral tuberculoma (n=1), pericardial effusion (n=1) and adenitis (n=3). Lymphopenia was present in three patients. Three out of the four patients received corticosteroid. Outcome was favorable in three patients. CONCLUSION: Pardoxical reactions are more common in patients who present with extrapulmonary tuberculosis. Intracerebral tuberculomas and spondylitis may be asymptomatic. Prescription of corticosteroids remains controversial except for intracerebral tuberculoma.

Effect of heart failure on dipeptidyl peptidase IV activity in plasma of dogs.

BACKGROUND: In congestive heart failure (HF), plasma B-type natriuretic peptide (BNP) seems devoid of biological effectiveness. BNP(1-32) could be truncated into BNP(3-32) by dipeptidyl peptidase IV (DPP4), and BNP(3-32) has reduced biological activities. HYPOTHESIS: Increased DPP4 activity is associated with pathophysiology of HF. ANIMALS: One hundred twenty-eight client-owned dogs and 9 experimental Beagles from the Clinical Veterinary Unit of the University of Liège. METHODS: We prospectively measured plasma DPP4 activity in 5 groups of dogs: normal growing dogs (n = 21), normal adult dogs (n = 60), healthy Beagle (n = 9), dogs with myxomatous mitral valve disease (n = 35), and dogs with dilated cardiomyopathy (n = 12). The final diagnosis and the severity of HF were determined by Doppler echocardiography. Plasma DPP4 activity was measured kinetically by a fluorimetric method. RESULTS: In growing dogs, DPP4 activity was higher than in adults (P < .001) and inversely correlated with age (r = -0.57, P < .01). In adults, DPP4 activity increased linearly with body weight (r = 0.39, P < .01), but there was no influence of age or sex. No effect of the circadian rhythm was noted. DPP4 activity was significantly higher in HF ISACHC I (16.3 ± 1.14 U/L) compared with healthy adults (12.4 ± 0.65 U/L, P < .05) and HF ISACHC III (11.0 ± 1.50 U/L, P < .05). Mean DPP4 activity in ISACHC II was 15.1 ± 1.4 U/L. CONCLUSION AND CLINICAL IMPORTANCE: We did not find evidence that plasma DPP4 activity is responsible for the "BNP resistance" in overt congestive HF, but it may be implicated in early stages.

[Lupus nephritis associated with common variable immunodeficiency: favourable outcome with intravenous immunoglobulin treatment]. / Néphropathie lupique liée à un déficit immunitaire commun variable d'évolution favorable sous immunoglobulines intraveineuses.

We report a 24-year-old woman who presented with a nephrotic syndrome as the revealing manifestation of systemic lupus erythematosus (SLE) and an associated hypogammaglobulinemia related to a common variable immunodeficiency (CVID). Outcome of SLE was favourable with intravenous immunoglobulin treatment solely. Relationships between SLE and CVID are discussed.

Purification, refolding and characterization of the trimeric Omp2a outer membrane porin from Brucella melitensis.

Brucella melitensis is a gram-negative bacteria known to cause brucellosis and to produce severe infections in humans. Whilst brucella's outer membrane proteins have been extensively studied due to their potential role as antigens or virulence factors, their function is still poorly understood at the structural level, as the 3D structure of Brucella ß-barrel membrane proteins are still unknown. In this context, the B. melitensis trimeric Omp2a porin has been overexpressed and refolded in n-dodecyl-ß-d-maltopyranoside. We here show that this refolding process is insensitive to urea but is temperature- and ionic strength-dependent. Reassembled species were characterized by fluorescence, size-exclusion chromatography and circular dichroism. A refolding mechanism is proposed, suggesting that Omp2a first refolds under a monomeric form and then self-associates into a trimeric state. This first complete in vitro refolding of a membrane protein from B. melitensis shall eventually lead to functional and 3D structure determination.

Theoretical study of the tautomerism in the one-electron oxidized guanine-cytosine base pair.

Ionizing radiation on DNA mainly generates one-electron oxidized guanine-cytosine base pair (G(+·):C), and in the present paper we study all possible tautomers of G(+·):C by using ab initio approaches. Our calculations reveal that the tautomeric equilibrium follows a peculiar path, characterized by a stepwise mechanism: first the proton in the central hydrogen bond N1(G)-H1-N3(C) migrates from guanine to cytosine, and then the cytosine cation releases one proton from its amino group. During this second step, water acts as a proton acceptor, localizing the positive charge on one of the water molecules interacting with the guanine radical. In agreement with experimental findings, the computed energy barriers show that the deprotonation of the cytosine cation is the speed-limiting step in the tautomeric equilibrium. The influence of the number of water molecules incorporated in the theoretical model is analyzed in detail. The evolution of electronic properties along the reaction path is also discussed on the basis of partial atomic charges and spin density distributions. This work demonstrates that water indeed plays a crucial role in the tautomeric equilibra of base pairs.

Intermolecular proton transfer in microhydrated guanine-cytosine base pairs: a new mechanism for spontaneous mutation in DNA.

Accurate calculations of the double proton transfer (DPT) in the adenine-thymine base pair (AT) were presented in a previous work [J. Phys. Chem. A 2009, 113, 7892.] where we demonstrated that the mechanism of the reaction in solution is strongly affected by surrounding water. Here we extend our methodology to the guanine-cytosine base pair (GC), for which it turns out that the proton transfer in the gas phase is a synchronous concerted mechanism. The O(G)-H-N(C) hydrogen bond strength emerges as the key parameter in this process, to the extent that complete transfer takes place by means of this hydrogen bond. Since the main effect of the molecular environment is precisely to weaken this bond, the direct proton transfer is not possible in solution, and thus the tautomeric equilibrium must be assisted by surrounding water molecules in an asynchronous concerted mechanism. This result demonstrates that water plays a crucial role in proton reactions. It does not act as a passive element but actually catalyzes the DPT.

Effects of hydration on the proton transfer mechanism in the adenine-thymine base pair.

We report the first density functional study of water catalytic effect in the double proton transfer (DPT) taking place in the adenine-thymine (AT) base pair. To gain more insight regarding the accuracy of several theoretical methods, the ability of various functionals and models for describing the geometry of this system has first been checked. According to our results, BP86/6-311++G(d,p) is the best option for describing the solvation effects in AT when applied to a two-water-molecule-featuring model. The two possible mechanisms for DPT in solution are explored: in the first one, water molecules only remain passive elements, whereas in the second one they are directly included in the reaction path. For the noncatalyzed mechanism, the stable structures constitute the canonical form of the base pair and the first proton transfer product. Nevertheless, by involving the two water molecules in the reaction, we found three stable species: canonical base pair, first proton transfer product, and double proton transfer product. Although the thermodynamic analysis confirms that AT does not contribute to spontaneous mutation through proton transfer catalyzed by surrounding water, our results suggest that microhydration may play a crucial role for DPT reaction in others DNA or RNA basis pair.

[Trochanteric bursitis, pelvic enthesopathy and giant cell arteritis]. / Bursite trochantérienne, enthésopathie pelvienne et maladie de Horton.

Giant cell arteritis, a large-sized vessel vasculitis, may be associated with musculoskeletal proximal (polymyalgia rheumatica) or distal manifestations. A 68-year-old woman, who had inflammatory pelvic girdle pain, was diagnosed with giant cell arteritis and was successfully treated with corticosteroids. The magnetic resonance imaging and ultrasonography revealed a bilateral bursitis and pelvic girdle enthesopathy. Bursitis is the main anatomic lesion occurring in polymyalgia rheumatica and can be underlined by ultrasonography.

Plasma concentration of insulin-like growth factor I (IGF-I) in growing Ardenner horses suffering from juvenile digital degenerative osteoarthropathy.

Degenerative osteoarthropathy resulting in a reduced active lifespan was observed in Ardenner horses. In the context of joint biology, insulin-like growth factor I (IGF-I) is a potential candidate to affect the anabolism of cartilage matrix molecules. A group of 30 Ardenner horses reared under standardized conditions from weaning were evaluated periodically from 15 to 28 months of age to detect the early manifestations of the disease. At the end of this period, horses were classified in two pathological groups related to the degree of interphalangeal degenerative osteoarthropathy based on clinical and radiographic evaluations: healthy (46.7%) and pathological (53.3%) horses. Seven sequential blood samples were taken from each horse (during the evaluation period) to study the variation of IGF-I plasma concentration. We tested the variations of the IGF-I plasma concentration during growth, and the effect of sex and of pathological classes. Significant variations were observed during the research period, with a maximum value corresponding to spring and a minimum in autumn. A significant reduction of the IGF-I plasma concentration was also observed in the pathological horses (433.5 +/- 19.5 ng/ml) compared to the healthy horses (493.9 +/- 18.2 ng/ml). An alteration in the level of this growth factor could induce a disregulation of the mechanisms involved in the local control of joint and bone tissue development.

Brain stem auditory potentials evoked by clicks in the presence of high-pass filtered noise in dogs.

This study evaluates the effects of a high-frequency hearing loss simulated by the high-pass-noise masking method, on the click-evoked brain stem-evoked potentials (BAEP) characteristics in dogs. BAEP were obtained in response to rarefaction and condensation click stimuli from 60 dB normal hearing level (NHL, corresponding to 89 dB sound pressure level) to wave V threshold, using steps of 5 dB in eleven 58 to 80-day-old Beagle puppies. Responses were added, providing an equivalent to alternate polarity clicks, and subtracted, providing the rarefaction-condensation potential (RCDP). The procedure was repeated while constant level, high-pass filtered (HPF) noise was superposed to the click. Cut-off frequencies of the successively used filters were 8, 4, 2 and 1 kHz. For each condition, wave V and RCDP thresholds, and slope of the wave V latency-intensity curve (LIC) were collected. The intensity range at which RCDP could not be recorded (pre-RCDP range) was calculated. Compared with the no noise condition, the pre-RCDP range significantly diminished and the wave V threshold significantly increased when the superposed HPF noise reached the 4 kHz area. Wave V LIC slope became significantly steeper with the 2 kHz HPF noise. In this non-invasive model of high-frequency hearing loss, impaired hearing of frequencies from 8 kHz and above escaped detection through click BAEP study in dogs. Frequencies above 13 kHz were however not specifically addressed in this study.

Examination of non-genetic factors affecting the growth performance of djallonke sheep in soudanian zone at the Okpara breeding farm of Benin.

A study was carried out at the Okpara breeding farm in Benin. Records on 558 lambs of the Djallonke sheep breed, born from 1997 to 2000, were used to determine the weekly growth curve from birth up to 119 days of age. Non-genetic factors affecting lamb weights at birth and at 30, 60, 90 and 120 days and average daily gains from 0 to 30 days, from 0 to 60 days, from 0 to 90 days and from 0 to 120 days were investigated. A linear model comprising the fixed effects of birth season, birth year, parity number of ewe and sex of lambs was used for analysis of variance by least squares. All fixed effects were significant for weight at 30 and 60 days and average daily gains at 30 days, with the exception of the parity of the ewe for birth weight, weight and average daily gain at 90 days. All fixed effects tended to cancel out for weight and average daily gains by 120 days. Lambs born in the dry season were the heaviest. Single lambs and male lambs were heavier than twins and females. Lambs from ewes of 3rd and 4th parity were heavier, with higher, average daily gains.

Differential scanning calorimetry in life science: thermodynamics, stability, molecular recognition and application in drug design.

All biological phenomena depend on molecular recognition, which is either intermolecular like in ligand binding to a macromolecule or intramolecular like in protein folding. As a result, understanding the relationship between the structure of proteins and the energetics of their stability and binding with others (bio)molecules is a very interesting point in biochemistry and biotechnology. It is essential to the engineering of stable proteins and to the structure-based design of pharmaceutical ligands. The parameter generally used to characterize the stability of a system (the folded and unfolded state of the protein for example) is the equilibrium constant (K) or the free energy (deltaG(o)), which is the sum of enthalpic (deltaH(o)) and entropic (deltaS(o)) terms. These parameters are temperature dependent through the heat capacity change (deltaCp). The thermodynamic parameters deltaH(o) and deltaCp can be derived from spectroscopic experiments, using the van't Hoff method, or measured directly using calorimetry. Along with isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC) is a powerful method, less described than ITC, for measuring directly the thermodynamic parameters which characterize biomolecules. In this article, we summarize the principal thermodynamics parameters, describe the DSC approach and review some systems to which it has been applied. DSC is much used for the study of the stability and the folding of biomolecules, but it can also be applied in order to understand biomolecular interactions and can thus be an interesting technique in the process of drug design.

Structural approach for COX-2 inhibition.

The design of selective COX-2 inhibitors is a new approach to obtain potent, anti-inflammatory drugs but with less side effects. Several families of such inhibitors were reported in literature. In this review, the drug design processes used to understand their binding mode and the origin of selectivity of these compounds are described.