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Larvae of the disease vector mosquito, Aedes aegypti (L.) readily develop in ammonia rich sewage in the British Virgin Islands. To understand how the larvae survive in ammonia levels that are lethal to most animals, an examination of ammonia excretory physiology in larvae collected from septic-water and freshwater was carried out. A. aegypti larvae were found to be remarkably plastic in dealing with high external ammonia through the modulation of NH4+ excretion at the anal papillae, measured using the scanning ion-selective electrode technique (SIET), and NH4+ secretion in the primary urine by the Malpighian tubules when developing in septicwater. Ammonia transporters, Amt and Rh proteins, are expressed in ionoregulatory and excretory organs, with increases in Rh protein, Na+-K+-ATPase, and V-type-H+-ATPase expression observed in the Malpighian tubules, hindgut, and anal papillae in septic-water larvae. A comparative approach using laboratory A. aegypti larvae reared in high ammonia septic-water revealed similar responses to collected A. aegypti with regard to altered ammonia secretion and hemolymph ion composition. Results suggest that the observed alterations in excretory physiology of larvae developing in septic-water is a consequence of the high ammonia levels and that A. aegypti larvae may rely on ammonia transporting proteins coupled to active transport to survive in septic-water.

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD). Data on use of prostanoids in this particular subset of patients are lacking. We aimed to describe the characteristics of patients with PAH-CTD treated with prostanoids and the outcomes under treatment.In this multicenter retrospective study, all patients treated with prostanoids since 2006 were included. Data on PAH and CTD were collected at the time of prostanoid introduction and under treatment.Twenty-one patients were included, of whom 20 (95%) had limited cutaneous systemic sclerosis. Nineteen patients were treated with oral monotherapy or combination before addition of prostanoid. Treprostinil was the most used molecule (57% of patients). At the time of prostanoid introduction, 90% of patients were considered at high risk for death. Among patients who had right heart catheterization during follow-up, there was no significant difference in haemodynamics. No extrarespiratory worsening of the CTD was reported. The 1-year survival under prostanoid was 62%. In univariate analysis, NYHA functional class was associated with survival under treatment.This study provides original data on use of prostanoids in a cohort consisting mainly of systemic sclerosis. It underlines the difficulty to achieve a standardized assessment in this subset of patients. Safety profile was comparable with data reported in idiopathic PAH.

Pharmaceutical prescription in systemic sclerosis is guided by national and international recommendations. This study's primary objective was to describe and analyze these prescriptions among patients of our cohort. We also aimed to assess drug compliance among our patients.This is a monocentric observational study on two cohorts of patients with systemic sclerosis; a primary cohort comprising ambulatory patients, who were prospectively included, with exhaustive prescription's data collection; and a secondary cohort included patients asked to fill in a self-questionnaire on treatment compliance.The main cohort included 157 patients, including 31 cases of diffuse systemic sclerosis. A vasodilator drug for Raynaud's phenomenon was prescribed in 75 patients (47.9%) and a specific treatment for pulmonary arterial hypertension in 10 patients (6.4%). Immuno-modulators/immunosuppressants was prescribed in 62 patients (39.5%), who received prednisone (n=37, 23.6%), mycophenolate mofetil (n=14, 8.9%), hydroxychloroquine (n=12, 7.6%) and colchicine (n=22, 14%). Treatment for "gastro-intestinal tract involvement" was prescribed for 106 patients (67.5%) and treatment of a scleroderma renal crisis with an angiotensin-converting enzyme inhibitor for 6 patients (3.8%). Among the 42 patients in the secondary cohort, 21.4% reported a good compliance, mostly older patients (P=0.045) or those who had not experienced adverse events (P=0.009).This study provides original real-life data illustrating the heterogeneity of prescription habits in systemic sclerosis. As previously reported, treatment compliance was insufficient.

Calcium levels are declining in eastern North American and western European lakes. This widespread issue is affecting the composition of crustacean zooplankton communities, as the presence and abundance of several calcium-rich daphniid species are declining, while two other daphniids, D. catawba and D. ambigua, that apparently tolerate low calcium environments, are prospering. The physiological basis for low calcium tolerance of these daphniids is unknown. In this study the presence of one Ca-rich (D. pulicaria) and one Ca-poor (D. ambigua) daphniid species in Canadian Shield lakes is assessed in relation to lake water Ca levels. The occurrence of D. ambigua was independent of Ca levels in Ontario lakes, whereas D. pulicaria was more likely to occur in lakes with relatively more Ca. In the laboratory, D. ambigua maintained lower levels of hemolymph Ca2+ across a range of low Ca levels (0.7 to 7 mg l−1) compared with D. pulicaria. The hemolymph pH remained steady across this Ca gradient in D. ambigua while it was significantly more acidic in D. pulicaria in the two lowest Ca treatments. While Ca2+ uptake was observed adjacent to the surface of D. ambigua individuals, Ca2+ loss was observed for D. pulicaria assayed under moderately high Ca levels. Based on these observations we propose that D. ambigua is able to survive in low Ca lakes by maintaining low free ionic Ca2+ levels in the hemolymph which minimizes the Ca gradient across the body wall in low Ca water thus limiting overall Ca loss and facilitating Ca2+ uptake.

Resume Introduction Le but de ce travail etait de decrire les particularites de la sclerodermie systemique (ScS) quand le diagnostic est fait apres l’âge de 70 ans. Patients et methodes Il s’agit d’une etude retrospective des patients âges de plus de 70 ans au moment du diagnostic de ScS, suivis dans un service de medecine interne entre 2000 et 2015. Les co-morbidites et les caracteristiques demographiques et cliniques ont ete analysees, ainsi que la survie a 1, 2 et 3 ans. Resultats Sur les 246 cas de ScS de notre cohorte, 27 (11 %) ont ete inclus (89 % de femmes, âges de 78,3 ± 4,5 ans). Une neoplasie synchrone etait notee chez 3 patients. La ScS etait majoritairement cutanee limitee (24/27), avec des telangiectasies (63 %), un reflux gastro-oesophagien (59 %), des ulceres digitaux (22 %), et associee a un anticorps anti-centromeres (69 % des cas). L’atteinte interstitielle pulmonaire etait peu frequente (29 %). Une hypertension arterielle pulmonaire (HTAP) etait suspectee des le diagnostic de ScS dans 14 cas (52 %), mais seuls 5 patients ont eu un catheterisme cardiaque, montrant une HTAP severe dans 3 cas. La survie etait de 85,2 % a 1 an et 66,7 % a 3 ans ; elle etait moins bonne en cas de suspicion d’HTAP (respectivement 78,6 % et 57,1 %). Conclusion Les cas de ScS diagnostiquee apres 70 ans sont majoritairement des formes cutanees limitees. Une suspicion d’HTAP est frequente, representant plus d’un cas sur 2, et l’HTAP est un mode d’entree dans la maladie a cet âge. L’association a un cancer synchrone est possible. La survie est mediocre.

The anal papillae of mosquito larvae are osmoregulatory organs in direct contact with the external aquatic environment that actively sequester ions and take up water in dilute freshwater. In the disease vector Aedes aegypti mechanisms of ion, water and ammonia transport have only been partially resolved. Furthermore, A. aegypti larvae are known to reside in high ammonia sewage and high salt brackish waters, and understanding of anal papillae function in these conditions is in its infancy. The objective of this study was to identify the complement of ion and water transport genes expressed by the anal papillae of freshwater larvae by sequencing their transcriptome, and comparing their expression in anal papillae of larvae abruptly transferred to brackish water for 24 h. Results identified a number of ion and water transport proteins, ammonia detoxifying enzymes, a full suite of xenobiotic detoxifying enzymes and transporters, and G-protein coupled receptors of specific hormones. We identified a marked increase in transcript and protein abundance of aquaporin AaAQP2 in the anal papillae with abrupt transfer to brackish water. We present an updated and more comprehensive model for ion and water transport with additional putative transporters for Na+ and Cl- uptake in the anal papillae. These are organs which are actively engaged in Na+, Cl- and water uptake and regulation when the aquatic larvae encounter fluctuating salinities over the course of their development. Furthermore the transcriptome of the anal papillae includes a full set of xenobiotic detoxification genes suggesting that these are important detoxification organs which is particularly important when larvae reside in polluted water.

The mosquito Aedes aegypti vectors the arboviral diseases yellow fever, dengue, Zika and chikungunya. Larvae are usually found developing in freshwater; however, more recently they have been increasingly found in brackish water, potential habitats which are traditionally ignored by mosquito control programs. Aedes aegypti larvae are osmo-regulators maintaining their hemolymph osmolarity in a range of ~ 250 to 300 mOsmol l-1. In freshwater, the larvae must excrete excess water while conserving ions while in brackish water, they must alleviate an accumulation of salts. The compensatory physiological mechanisms must involve the transport of ions and water but little is known about the water transport mechanisms in the osmoregulatory organs of these larvae. Water traverses cellular membranes predominantly through transmembrane proteins named aquaporins (AQPs) and Aedes aegypti possesses 6 AQP homologues (AaAQP1 to 6). The objective of this study was to determine if larvae that develop in freshwater or brackish water have differential aquaporin expression in osmoregulatory organs, which could inform us about the relative importance and function of aquaporins to mosquito survival under these different osmotic conditions. We found that AaAQP transcript abundance was similar in organs of freshwater and brackish water mosquito larvae. Furthermore, in the Malpighian tubules and hindgut AaAQP protein abundance was unaffected by the rearing conditions, but in the gastric caeca the protein level of one aquaporin, AaAQP1 was elevated in brackish water. We found that AaAQP1 was expressed apically while AaAQP4 and AaAQP5 were found to be apical and/or basal in the epithelia of osmoregulatory organs. Overall, the results suggest that aquaporin expression in the osmoregulatory organs is mostly consistent between larvae that are developing in freshwater and brackish water. This suggests that aquaporins may not have major roles in adapting to longterm survival in brackish water or that aquaporin function may be regulated by other mechanisms like post-translational modifications.

Background Pleuroparenchymal fibroelastosis (PPFE) is a very rare interstitial lung disease (ILD) characterized by progressive fibrotic lesions of the visceral pleura and the sub-pleural parenchyma, affecting predominantly the upper lobes. PPFE may occur in different contextes like bone marrow or lung transplantations, but also in the context of telomeropathy with mutations of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) or regulator of telomere elongation helicase 1 (RTEL1) genes. PPFE-like lesions have recently been described in patients with connective tissue disease (CTD)-related ILD. We report here the first detailed case of PPFE associated to systemic sclerosis (SSc) in a woman free of telomeropathy mutations. Case presentation A caucasian 46 year old woman was followed for SSc in a limited form with anti-centromere Ab since 1998, and seen in 2008 for a routine visit. Her SSc was stable, and she had no respiratory signs. Pulmonary function tests showed an isolated decreased cTLCO at 55.9% (of predicted value). Cardiac ultrasonography was normal. Thoracic CT-scan showed upper lobes predominant mild and focal pleural and subpleural thickenings, suggestive of PPFE, with a slight worsening at 8 years of follow-up. She remained clinically stable. Biology only found a moderate and stable peripheral thrombocytopenia, and sequencing analysis did not find any mutations in TERT and TERC genes. Conclusions ILD is frequent in SSc but isolated PPFE has never been described so far. In our case, PPFE is not related to telomeropathy, has indolent outcome and seems to have good prognosis. PPFE might be an extremely rare form of SSc-related ILD, although a fortuitous association remains possible.

The larvae of the mosquito Aedes aegypti inhabit ammonia rich septic tanks in tropical regions of the world that make extensive use of these systems, explaining the prevalence of disease during dry seasons. Since ammonia (NH3/NH4+) is toxic to animals, an understanding of the physiological mechanisms of ammonia excretion permitting the survival of A. aegypti larvae in high ammonia environments is important. We have characterized a novel ammonia transporter, AeAmt2, belonging to the Amt/MEP/Rh family of ammonia transporters. Based on the amino acid sequence, the predicted topology of AeAmt2 consists of 11 transmembrane helices with an extracellular N-terminus and a cytoplasmic C-terminus region. Alignment of the predicted AeAmt2 amino acid sequence with other Amt/MEP proteins from plants, bacteria, and yeast highlights the presence of conserved residues characteristic of ammonia conducting channels in this protein. AeAmt2 is expressed in the ionoregulatory anal papillae of A. aegypti larvae where it is localized to the apical membrane of the epithelium. dsRNA-mediated knockdown of AeAmt2 results in a significant decrease in NH4+ efflux from the anal papillae, suggesting a key role in facilitating ammonia excretion. The effect of high environmental ammonia (HEA) on expression of AeAmt2, along with previously characterized AeAmt1, AeRh50-1, and AeRh50-2 in the anal papillae was investigated. We show that changes in expression of ammonia transporters occur in response to acute and chronic exposure to HEA, which reflects the importance of these transporters in the physiology of life in high ammonia habitats.

The larvae of the mosquito Aedes aegypti inhabit ammonia rich septic tanks in tropical regions of the world that make extensive use of these systems, explaining the prevalence of disease during dry seasons. Since ammonia (NH3/NH4+) is toxic to animals, an understanding of the physiological mechanisms of ammonia excretion permitting the survival of A. aegypti larvae in high ammonia environments is important. We have characterized a novel ammonia transporter, AeAmt2, belonging to the Amt/MEP/Rh family of ammonia transporters. Based on the amino acid sequence, the predicted topology of AeAmt2 consists of 11 transmembrane helices with an extracellular N-terminus and a cytoplasmic C-terminus region. Alignment of the predicted AeAmt2 amino acid sequence with other Amt/MEP proteins from plants, bacteria, and yeast highlights the presence of conserved residues characteristic of ammonia conducting channels in this protein. AeAmt2 is expressed in the ionoregulatory anal papillae of A. aegypti larvae where it is localized to the apical membrane of the epithelium. dsRNA-mediated knockdown of AeAmt2 results in a significant decrease in NH4+ efflux from the anal papillae, suggesting a key role in facilitating ammonia excretion. The effect of high environmental ammonia (HEA) on expression of AeAmt2, along with previously characterized AeAmt1, AeRh50-1, and AeRh50-2 in the anal papillae was investigated. We show that changes in expression of ammonia transporters occur in response to acute and chronic exposure to HEA, which reflects the importance of these transporters in the physiology of life in high ammonia habitats.

Calcium levels are declining in eastern North American and western European lakes. This widespread issue is affecting the composition of crustacean zooplankton communities, as the presence and abundance of several calcium-rich daphniid species are declining, while two other daphniids, D. catawba and D. ambigua, that apparently tolerate low calcium environments, are prospering. The physiological basis for low calcium tolerance of these daphniids is unknown. In this study the presence of one Ca-rich (D. pulicaria) and one Ca-poor (D. ambigua) daphniid species in Canadian Shield lakes is assessed in relation to lake water Ca levels. The occurrence of D. ambigua was independent of Ca levels in Ontario lakes, whereas D. pulicaria was more likely to occur in lakes with relatively more Ca. In the laboratory, D. ambigua maintained lower levels of hemolymph Ca

The aim of this study was to describe special features of patients with systemic sclerosis (SSc) diagnosed after the age of 70.This is a retrospective study of patients aged above 70 years at the time of diagnosis of SSc and followed at an internal medicine unit between 2000 and 2015. Co-morbidities and clinical characteristics were analyzed, as well as survival at 1, 2 and 3 years.Of 246 patients, 27 (11%) were included (89% women, 96% Caucasians, age 78.3±4.5 years). Synchronous cancer was noted in 3 patients. SSc was mostly limited cutaneous only (24/27), with telangiectasia (63%), gastroesophageal reflux (59%) and digital ulcers (22%), and was associated with anti-centromere antibody (69%). Interstitial lung disease was not frequent (29%). Pulmonary arterial hypertension (PAH) was suspected at diagnosis of SSc in 14 cases (52%), but only 5 patients had undergone heart catheterization, with severe PAH in 3 cases. Survival at 1 and 3 years was 85.2% and 66.7%, and was worse in the case of suspected PAH, at 78.6% and 57.1% respectively.Cases of SSc diagnosed after 70 years are mostly limited cutaneous forms. Suspicion of PAH is frequent, and PAH may be the main initial sign of the disease for patients at this age. There may be association with synchronous cancer. Survival is poor.

Introduction L’hypophosphoremie (hPho) est une anomalie biologique rare definie par un seuil de phosphore Observation Une patiente de 19 ans etait hospitalisee pour une boulimie evoluant depuis 3 ans, avec episodes de vomissements, d’utilisation de laxatifs et une potomanie avec un IMC a 17 kg/m2. Son traitement comprenait une supplementation calcique, une pilule œstroprogestative et des complements alimentaires. Elle presentait une anemie a 9,3 g/dl normocytaire (VGM a 85,5 fL). Le bilan retrouvait une denutrition : hypoprotidemie avec hypoalbuminemie a 32 g/L, une ferritine a 8 yg/L, une carence en vitamine D3. Les dosages de B12, folates, la calcemie, le bilan hepatique, le ionogramme et la fonction renale etaient normaux. La phosphoremie etait normale a 1,29 mmol/L. Une perfusion de 500 mg de CMF etait realisee. Six jours apres la perfusion, l’ionogramme montrait une hypophosphoremie a 0,55 mmol/L isolee. Le ionogramme urinaire retrouvait une phosphaturie a 15,6 mmol/L, une creatininurie a 6,1 mmol/L soit un taux de reabsorption du phosphore abaisse a 67 % (norme > 85 %). Le PH urinaire etait normal a 6 sans glycosurie, de meme que la PTH. Une supplementation en phosphore etait debutee par phosphoneuros 100 gouttes matin et soir et la supplementation par fer oral a ete reprise, permettant une normalisation du bilan en 1 mois. Quatre de nos patients recevant des perfusions de CMF sur les 3 mois suivants ont developpe une hypophosphoremie entre parfois profonde, resolutive par supplementation orale en phosphore. Discussion Les effets indesirables de la CMF tels que les cephalees, les nausees ou les reactions au point d’injection sont desormais bien connus. Les prescriptions croissantes de ce traitement en raison de son efficacite et sa duree d’injection courte ont permis l’identification de nouveaux effets indesirables notamment biologiques a type d’hPho qui sont desormais bien documentes. Fierz et al. rapportent un cas similaire d’hPho severe a 0,18 mmol/L chez une jeune femme presentant un trouble du comportement alimentaire [1] . Ils suggerent d’augmenter les apports alimentaires en phosphate avant et au cours de la supplementation martiale intraveineuse et d’utiliser la CMF avec prudence chez les patients presentant une malnutrition. Klein et al. rapportent un cas d’hPho chez un patient suivi pour une maladie de Crohn recevant des perfusions regulieres de CMF ayant developpe une osteomalacie ayant regresse apres arret des perfusions et la supplementation en phosphore [2] . Ils soulevent ainsi le probleme du risque d’osteomalacie chez les patients recevant des perfusions intraveineuses de fer de facon reguliere et presentant des hypophosphatemie severe et asymptomatique. Zoller et al. insistent egalement sur ce risque d’osteomalacie et precisent le mecanisme qui serait en lien avec une augmentation de l’excretion renale du phosphore mediee par le FGF23 des fibroblastes [3] . Il semblerait que cet effet indesirable soit plus specifique au CMF puisqu’un essai clinique randomise multicentrique comparant ferumoxytol versus CMF mettait en evidence une hypophosphatemie dans 0,4 % dans le groupe ferumoxytol et 38,7 % dans le CMF avec une diminution du taux moyen de phosphore de 40 % a 2 semaines dans le groupe CMF. Conclusion L’hypophosphoremie est un effet indesirable frequent et peu connu sous CMF qu’il convient de depister du fait du son caractere asymptomatique et des complications potentielles notamment l’osteomalacie.

Objectif Discuter l’interet d’explorations complementaires, dans le bilan de thrombophilie constitutionnelle, avec mise en evidence d’un taux limite ou fluctuant d’antithrombine, par dosages en antigene et en activite puis par analyse genetique. Materiel et methode Un patient de 30 ans presente en 2001, de facon spontanee, un 1er episode de thrombose veineuse poplitee gauche etendue a la veine femorale superficielle, avec forte suspicion d’embolie pulmonaire. Il n’a aucun autre antecedent, a 2 enfants en bonne sante et son pere a presente 2 thromboses veineuses profondes idiopathiques. Le bilan de thrombophilie realise chez le patient montrera une activite antithrombine a 68 %, recontrolee a 65 %. Le bilan de thrombophilie chez sa mere est negatif. Chez son pere, une resistance a la proteine C activee est retrouvee mais le dosage de l’antithrombine n’a pas ete realise. Le patient est traite par antivitamine K au long cours. En 2016, la question de l’anticoagulation au long cours se pose, avec la notion d’un doute sur un deficit en antithrombine. Il est decide de realiser un complement de bilan de thrombophilie et un controle du dosage de l’antithrombine afin de conclure sur le statut du patient. Resultats Le controle du bilan de thrombophilie est negatif hormis une mutation du facteur V Leiden positive a l’etat heterozygote. L’activite antithrombine est a 60 %, l’antigene antithrombine a 73 % et l’antithrombine progressive a 60 %. Les dosages proches de la norme et variant selon les techniques utilisees, une analyse moleculaire est realisee. L’etude du gene de l’antithrombine montrera la presence a l’etat heterozygote de la mutation p.Leu178Pro. Il s’agit de la transition de thymine en cytosine sur l’exon 3 entrainant le changement de leucine a la position 178 en proline, aboutissant a une substitution faux sens, en faveur du caractere deletere susceptible d’expliquer le deficit du patient. Cette mutation n’a jamais ete decrite dans la litterature. Ce patient a risque thrombotique eleve poursuivra l’anticoagulation au long cours. Conclusion Les differents dosages d’antithrombine sont parfois discordants ou dans les limites de la norme chez des patients pourtant porteurs d’une anomalie de l’antithrombine a l’origine d’un risque thrombotique significatif. L’analyse moleculaire du gene peut dans certains cas etre une solution pour pallier cette difficulte diagnostique et permettre une decision therapeutique adaptee et un conseil genetique facilite.

Summary Background Imatinib mesylate is a potent inhibitor of platelet-derived growth factor and transforming growth factor-β signalling pathways which may play a role in systemic sclerosis (SSc)-associated skin changes. Objectives We aimed primarily at assessing the efficacy of imatinib mesylate in scleroderma skin fibrosis. Methods We performed a phase II double-blinded trial on patients with scleroderma with either morphoea involving > 20% of body surface area or SSc with extensive skin involvement: modified Rodnan Skin Score (mRSS) ≥ 20/51. Each patient was randomized to receive either imatinib mesylate 400 mg or placebo daily for a total of 6 months, and then was followed up 6 months after therapy discontinuation. Skin fibrosis was assessed by mRSS and measurement of the dermal thickness using skin biopsies performed at inclusion and at 6 months of treatment. In addition, quality of life (Dermatology Life Quality Index and modified Health Assessment Questionnaire for Scleroderma) was recorded at each visit, and pulmonary function before and after intervention. Results Twenty-eight patients were included in the study with a mean age of 48·9 years (range 30–71): 25 had a diagnosis of a SSc and three of diffuse cutaneous scleroderma. Demographic data, frequency of organ involvement of SSc and mRSS were comparable between groups. At 6 months, the proportion of variation of mRSS from inclusion was not statistically significantly different between the two groups (median +0·10 in imatinib group vs. −0·16 in placebo group, P = 0·098). Similarly, changes in dermal thickness, quality of life and diffusion capacity for carbon monoxide were not significantly different between groups. Conclusions This study failed to demonstrate the efficacy of imatinib 400 mg daily to improve skin fibrosis of diffuse scleroderma after 6 months of treatment based on validated outcome measurements.

Tungiasis is the parasitic skin disease caused by the sand flea Tunga penetrans, also called the jigger flea, found in most intertropical countries. The contamination occurs when walking barefoot in the sand: adult females actively burrow the foot epidermis leading to self-limited lesions responsible for itching or pain. The diagnosis is made on clinical observation and history of travelling to an endemic country. The simple treatment is surgical extraction of the flea.

Systemic lupus erythematosus (SLE) and small-sized vessel vasculitis are usually two distinguishable autoimmune diseases. However, a vasculitis may be found in the course SLE but rarely corresponds to an ANCA-associated vasculitis (AAV). We report four cases of de novo SLE associated with AAV, our aim being to discuss the clinical significance of this association. We included four patients fulfilling the criteria for both SLE and AAV and followed in two different university hospitals between 1996 and 2009. In light of a 20-year literature review (25 described clinical cases), we discussed the etiopathogeny of such an association. All patients presented a severe renal involvement (creatininemia ranging from 120 to 370 μmol/l) and thrombopenia (ranging from 45,000 to 137,000 platelets/mm(3)). The other main clinical symptoms were arthritis (n = 3), serositis (n = 2) and intra-alveolar hemorrhage (n = 2). An inflammatory syndrome was noticed at diagnosis in all cases. ANCAs were MPO-ANCAs in all cases. Two out of these four patients were also diagnosed with antiphospholipid syndrome. The frequency of this association seems not fortuitous. Although the etiopathogenic mechanisms of such an association remain to be more precisely described, several clinical, histological and immunological features support the hypothesis of the existence of a SLE-AAV overlapping syndrome. Moreover, clinicians must be aware of such an overlapping syndrome, notably because its initial presentation can be very severe.

Resume Introduction La face est une localisation frequente de la sclerose cutanee au cours de la sclerodermie systemique. Les principales manifestations stomatologiques comprennent la limitation de l’ouverture buccale, la xerostomie, l’atrophie cutanee, la nevralgie du V3. L’objectif de cette etude est de decrire les manifestations buccofaciales des patients sclerodermiques issus de notre cohorte. Methodes Entre mars et octobre 2006, une consultation de stomatologie a ete incluse dans le suivi systematique des patients sclerodermiques vus en consultation ou en hopital de jour de medecine interne et de dermatologie. Chaque patient a fait l’objet d’un recueil de donnees demographiques, cliniques et biologiques. Le recueil comportait la mesure de l’ouverture buccale, les tests au sucre et de Schirmer, l’analyse de l’orthopantomogramme, ainsi qu’une evaluation du retentissement des symptomes sur la qualite de vie par echelle visuelle analogique (EVA entre 0 et 10). Resultats Cette etude a inclus 30 patients (87 % de femmes, âge moyen 58,6 ± 13,6 ans). La sclerodermie systemique (cutanee limitee n = 20, diffuse n = 10) evoluait depuis huit ans en moyenne. Les manifestations buccofaciales identifiees etaient les suivantes : atrophie cutanee ( n = 28), rhagades peribuccales ( n = 25), telangiectasies ( n = 21), limitation de l’ouverture buccale ( n = 20), xerostomie ( n = 20), xerophtalmie ( n = 16), elargissement du ligament alveolo-dentaire ( n = 10), erosions osseuses ( n = 2), nevralgie du V3 ( n = 1). La xerostomie etait davantage percue comme genante (EVA moyenne = 3,8) que la limitation de l’ouverture buccale (EVA moyenne = 2,6). La xerostomie, decrite comme le second symptome le plus genant de la sclerodermie, etait significativement associee a la forme cutanee limitee ( p = 0,045) et a la presence d’anticorps anticentromere ( p = 0,002). La limitation de l’ouverture buccale etait correlee a l’atteinte œsophagienne ( p = 0,025). Conclusion Chez des patients sclerodermiques vus en consultation de stomatologie, les manifestations buccofaciales apparaissent frequentes et occasionnent une gene fonctionnelle majeure dominee par la limitation de l’ouverture buccale, souvent associee a une atteinte œsophagienne. La xerostomie est frequente et volontiers observee dans les formes limitees avec anticorps anticentromeres. L’evolution des anomalies radiologiques a type d’elargissement du ligament alveolo-dentaire (33 % des cas) ou d’osteolyse (7 %) est mal connue.

Objectif Les ischemies digitales (ID) sont une entite rare et heterogene auxquelles est cependant, confronte le medecin vasculaire ; l’ischemie du membre superieur est quarante fois moins frequente que celle des membres inferieurs. L’objectif de cette etude etait d’evaluer les etiologies, les traitements, les pronostics et l’evolution a long terme des ID dans la plus grande cohorte jamais rapportee. Malades et methodes Nous avons inclus les patients presentant des ischemies digitales, avec ou sans necrose, limitees ou non aux doigts sur la periode de janvier 2000 a decembre 2016 au sein du CHU de Nantes. Nous avons recueilli les donnees retrospectives portant sur l’etiologie, la recidive d’ID, les amputations digitales et la survie globale. Resultats Les ischemies digitales d’origine cardio-emboliques (IDCE) etaient l’etiologie principale avec 59 patients (18,3 %), suivie des patients atteints de sclerodermie systemique (SSc) avec 52 patients (16 %), les ID idiopathiques representaient 38 patients (11,7 %), les maladies de Buerger avec 30 patients (9,3 %), les causes iatrogeniques avec 30 patients (9,3 %) et les neoplasies avec 20 patients (6,2 %). Les patients avec une IDCE etaient significativement plus vieux et presentaient plus d’hypertension arterielle alors que les maladies de Buerger consommaient plus de tabac et de cannabis. Sur le plan clinique, les patients avec une IDCE avaient plus de pâleur des doigts et de douleur a la fois nociceptive et neuropathique alors que les SSc presentaient plus de necrose digitale. Le suivi a long terme a montre des recidives significativement plus frequentes dans le groupe SSc par rapport a tous les autres groupes (p Conclusion Dans cette etude, les etiologies principales d’ID etaient les cardiopathies emboligenes, la SSc et les ID idiopathiques. Cette etude montre une augmentation de l’etiologie iatrogenique en comparaison aux series d’ID precedentes. Les ID de la SSc sont associees a un mauvais pronostic local alors que les IDCE sont associees a un mauvais pronostic general. Les ID dans la SSc et la maladie de Buerger sont associees a plus de recidive.

Introduction La pre-eclampsie est une complication pouvant toucher 2 a 8 % des grossesses. Des etudes ont montre qu’elle serait responsable d’une majoration du risque cardiovasculaire a moyen et long terme. Elle est meme consideree dans les recommandations americaines comme un facteur de risque cardiovasculaire independant. Nous avons mis en place un parcours de soins, qui n’existait pas jusqu’alors, pour le suivi et le depistage du risque vasculaire dans cette population. Materiels et methodes Les obstetriciens du CHU et des cliniques de la region nantaise ont ete informes par courrier de la mise en place de cette filiere. Toutes les patientes ayant fait une pre-eclampsie sont eligibles a ce bilan qui se deroule lors d’une hospitalisation de jour, dans le service de medecine interne, durant laquelle un bilan clinique, biologique et morphologique evalue les facteurs de risque cardiovasculaire ainsi que les eventuelles complications de cet episode de pathologie fœtoplacentaire. Chaque patiente rencontre une dieteticienne. Enfin, les patientes sont egalement informees sur leur risque cardiovasculaire a moyen et long terme et la necessite de controler de maniere reguliere les autres facteurs de risque cardiovasculaire. Resultats Quarante-quatre patientes ayant presente une pre-eclampsie ont beneficie de ce bilan, entre les mois de janvier et septembre 2017. Nous avons mis en evidence 12 hypertensions arterielles (27 %) parmi lesquelles 8 relevaient d’un traitement antihypertenseur (18 %). Sept patientes presentaient une infiltration atheromateuse au niveau carotidien (16 %), dont 1 hypertendue. Une patiente presentait une hypertrophie ventriculaire gauche debutante et ne presentait ni hypertension ni atherome. Enfin, chez une patiente a ete diagnostiquee de maniere fortuite une thrombose de l’aorte. Nous n’avons pas diagnostique de diabete et le LDL cholesterol etait dans les normes chez les 44 patientes. Conclusion La mise en place de ce reseau de soins a ete bien recue par les obstetriciens et les patientes ayant presente un episode de pre-eclampsie. Le bilan systematique a permis de depister un nombre important d’hypertension arterielle persistante et precoce et d’atherosclerose debutante. Nous avons enfin delivre a toutes ces patientes, ainsi qu’aux medecins traitants, une information sur la necessite de poursuivre le suivi a moyen et long terme de l’ensemble des facteurs de risque cardiovasculaire.

Resume Introduction Les atteintes extracutanees et muqueuses des dermatoses neutrophiliques sont rares. Nous rapportons un cas de pyoderma gangrenosum (PG) cutaneomuqueux et systemique, revelant un syndrome myelodysplasique. Observation Un homme de 56 ans etait hospitalise pour un placard inflammatoire abdominal a centre ulcere, d’apparition rapide dans un contexte de fievre a 40 °C, d’odynophagie, d’amaigrissement et d’arthrite de cheville. Malgre un parage chirurgical abdominal et une bi-antibiotherapie, le patient restait febrile et l’ulceration grandissait. Ses bords etaient sureleves, violaces et necrotiques. L’examen montrait des lesions vegetantes, a bordure violacee, sur la levre inferieure et la langue. L’examen histologique des biopsies cutanee et muqueuse etait compatible avec le diagnostic de PG. Une tomodensitometrie (TDM) thoraco-abdominale trouvait un aspect de panniculite mesenterique et un syndrome interstitiel pulmonaire. La biopsie osteomedullaire montrait un aspect de leucemie myelomonocytaire chronique avec myelofibrose et exces de blastes. Une corticotherapie generale entrainait une apyrexie rapide ainsi que la cicatrisation des lesions cutanees, muqueuses et viscerales. Le patient presentait secondairement une acutisation en leucemie aigue myeloide de type 4, necessitant une allogreffe de moelle. Discussion Les atteintes extracutanees des dermatoses neutrophiliques sont rares, mais variees. Nous rapportons le cas d’un patient presentant un PG multifocal avec atteintes cutanee, muqueuse, articulaire, mesenterique et pulmonaire. Les lesions buccales au cours des PG sont souvent palatines ; elles sont frequemment associees aux maladies inflammatoires de l’intestin. Notre observation est originale par le caractere inaugural des lesions muqueuses, leur aspect bourgeonnant et leur topographie labiale et linguale.

Resume Introduction Il existe une discordance entre le faible nombre de cas d’atteintes cardiaques symptomatiques au cours de la granulomatose de Wegener (GW) rapportes dans la litterature et la frequence de ces atteintes dans les series autopsiques. Observations Quatre observations de GW avec manifestation cardiaque sont rapportees, associees a une atteinte des voies aeriennes (trois fois), renale (trois fois) ou pulmonaire (trois fois). Il s’agissait d’une cardiomyopathie dilatee chez deux patients, d’un bloc auriculoventriculaire complet avec pericardite (un patient) et d’une myopericardite (un patient). Un patient etait asymptomatique. Chez trois patients, l’atteinte cardiaque etait contemporaine de la decouverte de la GW. L’evolution etait defavorable pour trois patients. Conclusion La frequence des manifestations cardiaques dans la GW est probablement sous-estimee en raison de la grande variabilite de la presentation clinique. Ces manifestations sont associees a un mauvais pronostic. Un depistage cardiologique (clinique, electrocardiographique et echocardiographique) systematique et regulier est donc necessaire.

Resume Introduction La face est une localisation frequente de la sclerose cutanee au cours de la sclerodermie systemique. Les principales manifestations stomatologiques comprennent la limitation de l’ouverture buccale, la xerostomie, l’atrophie cutanee, la nevralgie du V3. L’objectif de cette etude est de decrire les manifestations buccofaciales des patients sclerodermiques issus de notre cohorte. Methodes Entre mars et octobre 2006, une consultation de stomatologie a ete incluse dans le suivi systematique des patients sclerodermiques vus en consultation ou en hopital de jour de medecine interne et de dermatologie. Chaque patient a fait l’objet d’un recueil de donnees demographiques, cliniques et biologiques. Le recueil comportait la mesure de l’ouverture buccale, les tests au sucre et de Schirmer, l’analyse de l’orthopantomogramme, ainsi qu’une evaluation du retentissement des symptomes sur la qualite de vie par echelle visuelle analogique (EVA entre 0 et 10). Resultats Cette etude a inclus 30 patients (87 % de femmes, âge moyen 58,6 ± 13,6 ans). La sclerodermie systemique (cutanee limitee n = 20, diffuse n = 10) evoluait depuis huit ans en moyenne. Les manifestations buccofaciales identifiees etaient les suivantes : atrophie cutanee (n = 28), rhagades peribuccales (n = 25), telangiectasies (n = 21), limitation de l’ouverture buccale (n = 20), xerostomie (n = 20), xerophtalmie (n = 16), elargissement du ligament alveolo-dentaire (n = 10), erosions osseuses (n = 2), nevralgie du V3 (n = 1). La xerostomie etait davantage percue comme genante (EVA moyenne = 3,8) que la limitation de l’ouverture buccale (EVA moyenne = 2,6). La xerostomie, decrite comme le second symptome le plus genant de la sclerodermie, etait significativement associee a la forme cutanee limitee (p = 0,045) et a la presence d’anticorps anticentromere (p = 0,002). La limitation de l’ouverture buccale etait correlee a l’atteinte œsophagienne (p = 0,025). Conclusion Chez des patients sclerodermiques vus en consultation de stomatologie, les manifestations buccofaciales apparaissent frequentes et occasionnent une gene fonctionnelle majeure dominee par la limitation de l’ouverture buccale, souvent associee a une atteinte œsophagienne. La xerostomie est frequente et volontiers observee dans les formes limitees avec anticorps anticentromeres. L’evolution des anomalies radiologiques a type d’elargissement du ligament alveolo-dentaire (33 % des cas) ou d’osteolyse (7 %) est mal connue.

In larval Aedes aegypti, transcripts of the Rhesus-like glycoproteins AeRh50-1 and AeRh50-2 have been detected in the anal papillae, sites of ammonia (NH3/NH4+) excretion; however, these putative ammonia transporters have not been previously localised or functionally characterized. In this study we show that the AeRh50s co-immunolocalise with apical V-type H+ ATPase as well as with basal Na+/K+ ATPase in the epithelium of anal papillae. The double-stranded RNA mediated knockdown of AeRh50-1 and AeRh50-2 resulted in a significant reduction in AeRh50 protein abundance in the anal papillae and this was coupled to decreased ammonia excretion. The knockdown of AeRh50-1 resulted in decreased hemolymph [NH4+] and pH whereas knockdown of AeRh50-2 had no effect on these parameters. We conclude that the AeRh50s are important contributors to ammonia excretion at the anal papillae of larval Aedes aegypti which may be the basis for their ability to inhabit areas with high ammonia levels.

Jaccoud's arthropathy (JA) is a chronic and non-erosive deforming arthropathy, usually affecting the hands. JA pathophysiology is poorly known but involves periarticular structures such as tendons and the joint capsule. JA is associated with various conditions including the connective tissue disease, especially systemic lupus erythematosis. JA has been rarely described and studied in systemic sclerosis.We report the clinical histories of 3 patients with systemic sclerosis (ScS) who developed JA. One patient had a systemic limited disease and the 2 others a cutaneous limited disease ; mean age of the patients was 79.3 years. Systemic sclerosis was diagnosed respectively 19, 1 and 21 years prior to the development of JA. One of the 3 patients had a past clinical history of discoid lupus. For 1 out of the 3 patients, JA appeared whereas the ScS was completely stable. The disease was still active in the 2 remaining patients, with concurrent pulmonary hypertension diagnosis. Deformities increased during years (Z thumbs, ulnar deviation), leading to mild to severe disability. No benefit from either prednisone (n=2) or a combination of prednisone and methotrexate (n=1) was obtained.We described 3 cases of Jaccoud's arthropathy among our scleroderma cohort of 296 patients (1%). This arthropathy worsens hand functional disability. Its pathophysiology is unknown and optimal therapeutic approach remains to establish.

Previous nuclear magnetic resonance (NMR) studies of unmodified and ψ39-modified tRNALys anticodon stem loops (ASLs) show that significant structural rearrangements must occur to attain a canonical anticodon loop conformation. The Escherichia coli tRNALys modifications mnm5s2U34 and t6A37 have indeed been shown to remodel the anticodon loop, although significant dynamic flexibility remains within the weakly stacked U35 and U36 anticodon residues. The present study examines the individual effects of mnm5s2U34, s2U34, t6A37, and Mg2+ on tRNALys ASLs to decipher how the E. coli modifications accomplish the noncanonical to canonical structural transition. We also investigated the effects of the corresponding human tRNALys,3 versions of the E. coli modifications, using NMR to analyze tRNA ASLs containing the nucleosides mcm5U34, mcm5s2U34, and ms2t6A37. The human wobble modification has a less dramatic loop remodeling effect, presumably because of the absence of a positive charge on the mcm5 side chain. Nonspe...