NLRP3 is involved in long bone edification and the maturation of osteogenic cells.

Overexpression of the nucleotide-binding leucine-rich repeat protein 3 (NLRP3) inflammasome in chronic auto-immune diseases leads to skeletal anomalies, with severe osteopenia due to the activation of osteoclasts. Reproducing this phenotype in Nlrp3 knock-in mice has provided insights into the role of NLRP3 in bone metabolism. We studied the role of NLRP3 in physiological bone development using a complete Nlrp3 knock-out mouse model. We found impaired skeletal development in Nlrp3-/- mice, resulting in a shorter stature than that of Nlrp3+/+  mice. These growth defects were associated with altered femur bone growth, characterized by a deficient growth plate and an osteopenic profile of the trabeculae. No differences in osteoclast recruitment or activity were observed. Instead, Nlrp3-/- femurs showed a less mineralized matrix in the trabeculae than those of Nlrp3+/+  mice, as well as less bone sialoprotein (BSP) expressing hypertrophic chondrocytes. In vitro, primary osteoblasts lacking NLRP3 expression showed defective mineralization, together with the downregulation of BSP expression. Finally, follow-up by micro-CT highlighted the role of NLPR3 in bone growth, occurring early in living mice, as the osteopenic phenotype diminishes over time. Overall, our data suggest that NLRP3 is involved in bone edification via the regulation of hypertrophic chondrocyte maturation and osteoblast activity. Furthermore, the defect appeared to be transitory, as the skeleton recovered with aging.

Virulence and enterobacterial repetitive intergenic consensus PCR of Vibrio alginolyticus strains isolated from Tunisian cultured gilthead sea bream and sea bass outbreaks.

Vibrio alginolyticus was isolated from the internal organs of diseased gilthead sea bream (Sparus aurata) and sea bass (Dicentrarchus labrax) cultured in two fish farms located on the Tunisian Mediterranean coast, from 2003 to 2005. After phenotypic characterisation, a selection of 34 isolates from gilthead sea bream and sea bass were molecularly typed by repetitive intergenic consensus PCR (ERIC-PCR) showing a high polymorphism among the isolated strains (19 genotypes). Most of the isolates were resistant to atleast two antimicrobial agents. All the tested strains were resistant to ampicillin. However, 91.17% were resistant to nitrofurantoin and 35.29% to tetracycline. Several strains isolated from diseased gilthead sea bream and sea bass were tested for virulence in both fish species by intraperitoneal injection. The selected isolates (n=7) were pathogenic for gilthead sea bream and sea bass. LD(50) values ranged from 5.01 x 10(4) to 6.20 x 10(7)CFU/fish. This is the first report on characterisation and virulence of V. alginolyticus for sea bass and sea bream in Tunisia.

[Infantile visceral leishmaniasis: difficult diagnosis in cases complicated by hemophagocytosis]. / Leishmaniose viscérale infantile: un diagnostic difficile en cas d'hémophagocytose associée.

BACKGROUND: Hemophagocytosis has already been reported in cases of visceral leishmaniasis and thus may complicate search for diagnosis. CASE REPORT: A previously healthy 2 year-old boy was referred for fever and splenomegaly with pancytopenia. An initial diagnosis of kala-azar was refuted because of absence of biological inflammatory syndrome, negativity of bone-marrow aspiration and splenic ponction and of specific serology. After three months of clinical deterioration and apparition of active hemophagocytosis, both bone marrow aspiration and specific serology for visceral leishmaniasis became positive. The boy was given sodium stibogluconate for 20 days; he improved gradually with complete and definitive remission. CONCLUSION: Diagnosis of visceral leishmaniasis may be difficult, even in countries where this condition is relatively frequent; the association with hemophagocytosis is possible and does not constitute a poor factor of prognosis if specific therapy is proposed.

[Imerslund-Najman-Grasbeck anemia. Apropos of a case]. / L'anémie d'Imerslund-Najman-Grasbeck. A propos d'un cas.

Imerslund-Najman-Grasbeck disease is a rare inherited megaloblastic anaemia secondary to a selective malabsorption of vitamin B12 by ileal enterocytes. The authors report on a 4 year-old tunisian girl who presented as visceral infantile leishmaniasis because of huge splenomegaly and major anaemia. The diagnosis of Imerslund disease was performed on the basis of the association of typical megaloblastic cells in the marrow, permanent proteinuria and favourable outcome under parenteral B12 administration. In addition, ther were no folate deficiency, no anti-intrinsic factor antibodies and no intrinsic factor deficiency. The outcome of the disease is always favourable if parenteral administration of vitamin B12 maintained.

[Infantile cystinosis. A new Tunisian case]. / Cystinose infantile. Une nouvelle observation tunisienne.

A case of cystinosis in a three and a half-year-old is reported. Suggestive manifestations included severe rickets, small stature, and complex renal tubule dysfunction meeting the criteria for secondary Fanconi syndrome. Diagnosis was established by the discovery of retinal lesions upon ophtalmologic evaluation and, above all, by the finding that intracellular leukocyte cystine levels were increased to 16 mumol of 1/2 cystine per gram protein. Cystinosis is severe because it inevitably leads to renal failure. Much hope is currently placed in the use of cysteamine to delay this and other complications. At present, early antenatal diagnosis during the first ten weeks of pregnancy is needed in high-risk families to allow elective termination of pregnancy within the legal time limit.