New Treatment Options in Lupus Nephritis.

The aim of this study is to report major recent progresses in the treatment of lupus nephritis (LN). Results of controlled randomized trials are discussed in view of the unmet needs in the field. Current treatments of LN are not satisfactory, with a disappointing proportion of 20-30% of patients achieving complete renal response within 6-12 months, and 5-20% developing end-stage kidney disease within ten years. Two drugs (belimumab and voclosporin) have been officially registered by the medical agencies as add on treatment of LN, a first-in-history success after decades of use of non-registered drugs and trial failures. Other targeted therapies (obinutuzumab and anifrolumab) are currently tested in Phase III trials, after interesting results in Phase II studies. Unanswered questions related to the use of these new drugs are discussed. Recent trials have opened new avenues for the treatment of LN which will hopefully reduce the rate of chronic kidney disease

Unusual cause of lymphadenopathy in a patient with systemic sclerosis.

Sirs, We report a rare association between histio cytic necrotising lymphadenitis, also called Kikuchi-Fujimoto disease (KFD), and systemic sclerosis. [...

Metal binding to ligands: cadmium complexes with glutathione revisited.

We studied the interaction of gamma-L-glutamyl-L-cysteinyl-glycine (glutathione, GSH) with cadmium ions (Cd(2+)) by first performing classical potentiometric pH titration measurements and then turning to additional spectroscopic methods. To estimate the residual concentrations of free cadmium, we studied the competition of glutathione with a Cd(2+)-sensitive dye, either an absorbing dye (murexide) or a fluorescent one (FluoZin-1), and consistent results were obtained with the two dyes. In KCl-containing Tes, Mops, or Tris buffer at pH 7.0 to 7.1 and 37 degrees C (and at a total Cd(2+) concentration of 0.01 mM), results suggest that free cadmium concentration is halved when the concentration of glutathione is approximately 0.05 mM; this mainly reflects the combined apparent dissociation constant for the Cd(glutathione) 1:1 complex under these conditions. To identify the other complexes formed, we used far-UV spectroscopy of the ligand-to-metal charge transfer absorption bands. The Cd(glutathione)(2) 1:2 complex predominated over the 1:1 complex only at high millimolar concentrations of total glutathione and not at low submillimolar concentrations of total glutathione. The apparent conditional constants derived from these spectroscopy results made it possible to discriminate between sets of absolute constants that would otherwise have simulated the pH titration data similarly well in this complicated system. Related experiments showed that although the Cl(-) ions in our media competed (modestly) with glutathione for binding to Cd(2+), the buffers we had chosen did not bind Cd(2+) significantly under our conditions. Our experiments also revealed that Cd(2+) may be adsorbed onto quartz or glass vessel walls, reducing the accuracy of theoretical predictions of the concentrations of species in solution. Lastly, the experiments confirmed the rapid kinetics of formation and dissociation of the UV-absorbing Cd(glutathione)(2) 1:2 complexes. The methods described here may be useful for biochemists needing to determine conditional binding constants for charge transfer metal-ligand complexes under their own conditions

L’atrophie musculaire induite par les glucocorticoïdes : présentation clinique, mécanismes physiopathologiques et implications thérapeutiques

Les glucocorticoïdes (GC) sont utilisés dans tous les domaines de la médecine pour leurs effets anti-inflammatoires et immunosuppresseurs. Leurs effets secondaires sont redoutés, notamment la myopathie cortisonique (MC). Celle-ci se caractérise par une atrophie musculaire s'installant de manière insidieuse, et joue un rôle pronostique important. La MC est liée au déséquilibre induit par les GC dans la balance entre synthèse et dégradation des protéines musculaires, en favorisant leur dégradation et inhibant leur synthèse. Nous proposons une revue des principaux mécanismes physiopathologiques de la MC, nous permettant d’élargir la discussion sur les potentielles cibles thérapeutiques telles que la myostatine, le récepteur de type IIB à l’activine, TRAF6 et REDD1. Enfin, des recommandations pratiques pour lutter contre la MC sont développées, dont l’exercice de résistance.[Glucocorticoid-induced muscle atrophy: clinical presentation, physiopathological mechanisms, and therapeutic implications] Glucocorticoids (GC) are used in all medical areas because of their antiinflammatory and immunosuppressive effects. Their undesirable effects are, however, much feared, in particular cortisone-induced myopathy (CD). This condition is characterized by insidious muscle atrophy, exhibiting an important prognostic role. CD is related to the GC-induced imbalance between muscle protein synthesis and degradation, promoting their degradation yet inhibiting their synthesis. We have herein undertaken a review focused on CD’s main pathophysiological mechanisms, along with a discussion on potential targets, such as myostatin, activin receptor Type IIB, TRAF6, and REDD1. To end with, practical recommendations for the fight against CD have been developed, including resistance exercises

Role of the yeast ABC transporter Yor1p in cadmium detoxification

Growth of yeast strains, either deleted for the vacuolar ABC transporterYcf1 or deleted for the plasma membrane ABC transporter Yor1p or overexpressing Yor1p, were compared for their sensitivity to cadmium. On solid medium cell death (or growth inhibition) was observed at cadmium concentrations higher than 100 mu M when yeasts were grown at 30 degrees C for 24 h. However, for all tested strains cell death (or growth inhibition) was already observed at 40 mu M cadmium when incubated at 23 degrees C for 60 h. Thus cadmium is more toxic to yeast at 23 degrees C than at 30 degrees C. At 23 'C, the Delta yor1 strain grew more slowly than the wild-type strain and the double Delta yor1, Delta ycfl deleted strain was much more sensitive to cadmium than each single Delta yor1 or Delta ycf1 deletant. Overexpression of Yor1p in a Delta ycf1 strain restores full growth. Cadmium uptake measurements show that Delta ycfl yeast strains expressing or overexpressing Yor1p store less cadmium than the corresponding Delta ycf1, Delta yor1 strain. The strains expressing Yor1p display an energy-dependent efflux of cadmium estimated for the yeast overexpressing Yor1p to be about 0.02 nmol Cd-109/mg protein/min. Yeast cells loaded with radiolabeled glutathione and then with radioactive cadmium displayed a twice-higher efflux of glutathione than that of cadmium suggesting that Yor1p transports both compounds as a bis-glutathionato-cadmium complex. All together, these results suggest that in addition to being accumulated in the yeast vacuole by Ycf1p, cadmium is also effluxed out of the cell by Yor1p. (c) 2006 Elsevier Masson SAS. All rights reserved

Prevalence and spectrum of SDHx mutations in pheochromocytoma and paraganglioma in patients from Belgium: an update

Since the early 2000s, the prevalence and spectrum of mutations in genes encoding subunits of succinate dehydrogenase (SDHx) were reported in large cohorts of patients with pheochromocytoma (PC) and paraganglioma (PGL) from most Western countries. Unfortunately, in Belgium, no equivalent work was performed thus far. Therefore, the aim of the work was to look for mutations in SDHx genes and genotype-phenotype correlations in patients with PC and/or PGL from Belgium. Screening of the coding parts of SDHx genes and deletion search were performed in all patients with PC and/or PGL referred to the Cliniques Universitaires Saint-Luc from 05/2003 to 05/2011. Genetic screening was performed in 59 unrelated head and neck (hn)PGLs (8 fami lial) and 53 PCs (7 extra-adrenal; 3 metastatic). In hnPGLs, 10 diff erent SDHD mutations (3 substitutions, 5 deletions, 2 splice site mutations) were detected in 16 patients, including 7 familial cases and 9 apparently sporadic cases. In the same subset, we found 8 diff erent SDHB mutations (5 substitutions, 1 splice ite mutation, 1 deletion, 1 duplication) in 10 patients with sporadic hnPGL without evidence of malignancy. No SDHx mutation was detected in patients harboring PCs and no SDHC mutation whatsoever. In conclusion, in our multicentric database of PC-PGLs from Belgium, (i) the prevalence of SDHx mutations was high in hnPGLs (44 % in the whole subset, 37 % of apparently sporadic cases); (ii) in sporadic cases, the prevalence of SDHB mutations was high (20 %), similar to that of SDHD (18 %); and (iii) no SDHx mutation was found in a subset of mostly adrenal, benign PCs

The Characteristics of Diverticular Disease in Caribbean Population: A Control Group Study

Background. Diverticulosis is not well characterized in the Caribbeans. Our aim was to compare the anatomical presentation of colonic diverticulosis in African Caribbeans (group AC) versus Europeans (group E) and severity. Methods. We conducted a prospective controlled study involving 274 patients admitted for lower gastrointestinal haemorrhage (LGIH) in France (center 1: Guadeloupe; center 2: La Roche-sur-Yon); 179 cases with diverticular haemorrhage, including 129 in group AC and 40 in group E. Exploration of the colon included a detailed assessment of diverticula using a dedicated endoscopic grid. Results. AC and E had similar characteristics in terms of age, gender, previous history of LGIH, body mass index, dietary habits, and medications, but AC had significantly poorer hemodynamic parameters at admission and required more blood transfusions (66.7% vs. 42.5%; p=0.01) during hospitalization. Out of the 169 patients included in the study, a complete exploration of the colon was achieved in 81% (N = 137) (AC, n = 106; E, n = 31), and revealed right-side diverticulosis in AC (in 90.6%, included into a pancolonic form in 73.6% vs. 35.5%; p=0.0002) and left-side diverticulosis in E (in 96.8%, isolated form in 58.1% vs. 9.4%, p=0.0002). These data were confirmed by a sensitivity analysis using an endoscopic grid in 92 patients, achieving a higher frequency and larger size of diverticula in AC. Conclusion. Our study has shown that diverticulosis was pancolonic in AC and more frequently associated with more severe haemorrhage than the left-sided diverticulosis of Europeans. This anatomical presentation may be driven by the genetic background more than the environment and diet

The Characteristics of Diverticular Disease in Caribbean Population: A Control Group Study

International audienceBACKGROUND: Diverticulosis is not well characterized in the Caribbeans. Our aim was to compare the anatomical presentation of colonic diverticulosis in African Caribbeans (group AC) versus Europeans (group E) and severity. METHODS: We conducted a prospective controlled study involving 274 patients admitted for lower gastrointestinal haemorrhage (LGIH) in France (center 1: Guadeloupe; center 2: La Roche-sur-Yon); 179 cases with diverticular haemorrhage, including 129 in group AC and 40 in group E. Exploration of the colon included a detailed assessment of diverticula using a dedicated endoscopic grid. RESULTS: AC and E had similar characteristics in terms of age, gender, previous history of LGIH, body mass index, dietary habits, and medications, but AC had significantly poorer hemodynamic parameters at admission and required more blood transfusions (66.7% vs. 42.5%; p=0.01) during hospitalization. Out of the 169 patients included in the study, a complete exploration of the colon was achieved in 81% (N = 137) (AC, n = 106; E, n = 31), and revealed right-side diverticulosis in AC (in 90.6%, included into a pancolonic form in 73.6% vs. 35.5%; p=0.0002) and left-side diverticulosis in E (in 96.8%, isolated form in 58.1% vs. 9.4%, p=0.0002). These data were confirmed by a sensitivity analysis using an endoscopic grid in 92 patients, achieving a higher frequency and larger size of diverticula in AC. CONCLUSION: Our study has shown that diverticulosis was pancolonic in AC and more frequently associated with more severe haemorrhage than the left-sided diverticulosis of Europeans. This anatomical presentation may be driven by the genetic background more than the environment and diet