Autoantibodies in systemic lupus erythematosus: spectrum and clinical associations

We have analysed the clinical features and autoantibody profile of 84 tunisian patients with newly diagnosed systemic lupus erythematosus (SLE). Antinuclear antibodies (ANA) were detected by an immunofluorescence method, anti-dsDNA and anti-cardiolipin (aCL) antibodies by ELISA, antinucleosome and anti-extractible nuclear antigens (or anti-ENA: anti-Sm, anti-RNP, anti-SSA and anti-SSB) by immunodot. The mean age of the patients was 29,9 years and the sex-ratio F/M was 6. The most common initial features were haematological (80%), rheumatological (78%) and cutaneous (75%) disorders. 59% of the patients had glomerular nephropathy. ANA were detected in 97.6%, antinucleosome in 78.6%, anti-dsDNA in 75%, anti-histones in 44%, anti-Sm in 36.9%, anti-RNP in 32.1%, anti-SSA in 54.8% and anti-SSB in 14.3% of patients. IgG and IgM aCL were detected in 45 and 40% of the patients respectively. The significant clinical associations were those of nephropathy and disease activity with anti-dsDNA and antinucleosome antibodies. Our results confirm the clinical polymorphism of SLE, the high frequency of antinucleosome antibodies at time of diagnosis and the predominance of anti-SSA among anti-ENA antibodies.     

Efficient Up-Conversion ZnO Co-Doped (Er,Yb) Nanopowders Synthesized via the Sol-Gel Process for Photovoltaic Applications

In this study, undoped and (Erbium, Ytterbium) co-doped ZnO nanopowders were prepared using the sol-gel method and the supercritical drying of ethyl alcohol. Doping ZnO nanopowders were elaborated with 5 mol% of Er (5 Er: ZnO), 5 mol% of Er and 5 mol% of Yb (5 Er, 5 Yb: ZnO), and 5 mol% of Er and 10 mol% of Yb (5 Er, 10 Yb: ZnO) concentrations. The effects of the Yb concentration on the structural, morphological, photoluminescent, and electrical properties of the ZnO nanopowders were investigated. The main findings of this work were the crystallinization of all of the nanopowders in a hexagonal Wurtzite structure with a spheroidal morphology and a size of 60 nm. Hence, the doping concentration would affect the crystallinity and the morphology of the ZnO nanopowder. The UC (Up-Conversion) emissions were investigated under a 980 nm excitation. It was observed that (Er, Yb: ZnO) exhibited green, ranging between 525 nm and 550 nm and red up-converted emissions of 655 nm, due to the efficient energy transfer process between Er³⁺ and Yb³⁺. The absolute quantum yield percentage (QY %) of the doped nanopowders was measured as a function of power density at each up-converted emission. This would prove that (5 Er, 5 Yb: ZnO) had the highest QY percentage value of 6.31 ± 0.2% at a power density of 15.7 W/cm². Additionally, it had the highest excited state lifetime for green and red emissions. Moreover, the Hall effect measures showed that the resistivity decreased while the electron mobility increased after doping, suggesting that most of rare earth ions were located in the interstitial positions. The carrier concentration increased after doping until (5 Er, 5 Yb: ZnO), suggesting that the Zn²⁺ ions substituted the RE³⁺ ions. Then, the carrier concentration decreased, suggesting that doping with higher concentrations would cause grain boundary defects. These findings would suggest that (5 Er, 5 Yb: ZnO) would have the best electrical properties and the lowest band gap energy (3.24 eV). Therefore, the presented preparation of the (Er, Yb: ZnO) nanopowders elaborated, using the sol-gel process would be a potential interesting material for UC applications.     

Unusual bone localization of sarcoidosis mimicking metastatic lesions: case report and review of literature

Sarcoidosis is a multisystem disease of unknown origin. Diagnosis remains challenging, based on organ site involvement, histological confirmation of non-caseating granuloma and an appropriate clinical syndrome. Granulomatous bone involvement is rare and may be ignored because it is usually asymptomatic. Vertebrae, ribs and skull localizations are rarely reported. We described an interesting case of a woman with chronic and multiorgan sarcoidosis with unusual bone localizations.     

A case study about the use of the prospective strategy in the scenarization of a pedagogical workshop

IntroductionPedagogical workshop planning is challenging especially when we aim to promote a reflective practice of the tutees. This practice has been widely discussed in the literature without a real consensus. Some authors reported oral exercises or anecdotes, other described writings or even storytelling. The aim of the authors was to describe the different steps performed by the tutors and to assess the tutees’ satisfaction.Material and methodsThis was a pilot study dealing with the use of the prospective strategy principles in order to plan a pedagogical workshop. Included participants were early academic teacher trainees.ResultsThe authors illustrated how they planned a pedagogical workshop using the prospective strategy and highlighted the satisfaction of the tutees.ConclusionProspective strategy is mainly used in economic field in order to change the future of the companies by acting on different intervening factors. Associating prospective strategy to pedagogical principles hasn’t been reported in the medical literature and seems to be available in order to induce reflective practice.     

Elliptocytogenic alpha I/36 spectrin Sfax lacks nine amino acids in helix 3 of repeat 4. Evidence for the activation of a cryptic 5'-splice site in exon 8 of spectrin alpha-gene.

Elliptocytogenic alpha I/36 spectrin Sfax is a new variant found in a Tunisian family. The alpha I/36 allele yielded a clinically manifest picture only when occurring in trans to a recently identified, low expression level polymorphism referred to as the alpha V/41 allele. Spectrin dimers were slightly increased in 4 degrees C extracts. On peptide maps, the alpha I domain split into two abnormal fragments of 36 and 33 Kd. The mutated alpha-chain represented 20% and 44% of total alpha-chain in alpha/alpha I/36 and alpha V/41/alpha I/36 heterozygotes, respectively. Peptide sequencing showed that the 36-Kd fragment started at Ala 357 and displayed a deletion extending from amino acids 363 to 371. The corresponding 27-nucleotide deletion was found in alpha-spectrin mRNA. However, exon 8 of spectrin alpha-gene failed to disclose this deletion. Instead, an A to G substitution appeared in position 3 of codon 362, leading to the occurrence of the critical GU dinucleotide within a cryptic 5'-splice site surrounding codon 362. This event would account for the splicing out of codons 363 to 371. The reading frame was preserved and even amino acid 362 (AGG, Arg) remained unaltered. As in most spectrin alpha-chain elliptocytogenic variants, the change involved a helix 3. This is the first elliptocytogenic mutation recorded in repeat alpha 4.     

State‐dependent blocking mechanism of Kv1.3 channels by the antimycobacterial drug clofazimine

Background and Purpose

K_v1.3 potassium channels are promising pharmaceutical targets for treating immune diseases as they modulate Ca²⁺ signalling in T cells by regulating the membrane potential and with it the driving force for Ca²⁺ influx. The antimycobacterial drug clofazimine has been demonstrated to attenuate antigen‐induced Ca²⁺ oscillations, suppress cytokine release and prevent skin graft rejection by inhibiting K_v1.3 channels with high potency and selectivity.

Experimental Approach

We used patch‐clamp methodology to investigate clofazimine''s mechanism of action in K_v1.3 channels expressed in HEK293 cells.

Key Results

Clofazimine blocked K_v1.3 channels by involving two discrete mechanisms, both of which contribute to effective suppression of channels: (i) a use‐dependent open‐channel block during long depolarizations, resulting in accelerated K⁺ current inactivation and (ii) a block of closed deactivated channels after channels were opened by brief depolarizations. Both modes of block were use‐dependent and state‐dependent in that they clearly required prior channel opening. The clofazimine‐sensitive closed‐deactivated state of the channel was distinct from the resting closed state because channels at hyperpolarized voltages were not inhibited by clofazimine. Neither were channels in the C‐type inactivated state significantly affected. K_v1.3 channels carrying the H399T mutation and lacking C‐type inactivation were insensitive to clofazimine block of the closed‐deactivated state, but retained their susceptibility to open‐channel block.

Conclusions and Implications

Given the prominent role of K_v1.3 in shaping Ca²⁺ oscillations, the use‐dependent and state‐dependent block of K_v1.3 channels by clofazimine offers therapeutic potential for selective immunosuppression in the context of autoimmune diseases in which K_v1.3‐expressing T cells play a significant role.

Abbreviations

CLF

clofazimine

FDA

Food and Drug Administration

IPI

interpulse intervals

WT

wild type

     

Pneumocystis carinii pneumonia in patients with hematologic malignancies: a descriptive study

Objectives. A retrospective multicentric study was conducted over a five-year period to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating hematologic malignancies.Results. The study included 60 HIV-negative patients with 18 non-Hodgkin's malignant lymphoma (30%), 13 chronic lymphocytic leukaemia (21.7%), 10 acute leukemia (16.6%), 5 multiple myeloma (8.3%), 4 Waldenstr?m's diseases (6.6%), 4 chronic myeloid leukemia (6.6%), 3 myelodysplasia (5%), 2 Hodgkin's diseases (3.3%) and 1 thrombopenia. Bronchoalveolar lavage was diagnostic in all patients. Forty-nine patients received cytotoxic drugs (81.7%), 25 (41.7%) a long-term corticotherapy and 15 (25%) underwent bone marrow transplantation. Twenty-seven patients (45%) required admission in the intensive care unit, 35 (58.3%) received an adjunctive corticotherapy and 18 mechanical ventilation (30%). Twenty patients (33.3%) died of PCP. A previous long-term corticotherapy (p=0.04), high respiratory (p=0.05) and pulse rates (p=0.02), elevated C reactive protein (p=0.01) and mechanical ventilation (OR=13.37; IC: 1.9-50) were associated with a poor prognosis. Adjunctive corticotherapy did not modify the prognosis.Conclusions. These results suggest that PCP can occur during the course of various hematologic malignancies, not only lymphoproliferative disorders. Prognosis remains poor. The diagnosis should be advocated more frequently and earlier to improve the prognosis.