[Treatment of systemic vasculitis]. / Traitement des vascularites systémiques.

Progress in the treatment of systemic vasculitis have permitted a decrease of mortality but with an increase in iatrogenic morbidity. Steroids remain the cornerstone of the treatment but precise modalities and other concomitant treatments are depending upon the type of vasculitis. In most cases, systemic vasculitis are primary and the treatment, although important, is symptomatic. However, in some cases such as hepatitis B virus-induced polyarteritis nodosa or hepatitis C virus-induced cryoglobulinemia, the treatment can be etiologic and is directed against the antigen responsible for the systemic vasculitis. In the future, a better understanding of pathological mechanisms, particularly of etiologic factors, and new treatment such as monoclonal antibodies should increase the prognosis of systemic vasculitis.

Regulation of the cytosolic aspartate aminotransferase housekeeping gene promoter by glucocorticoids, cAMP, and insulin.

The cytosolic aspartate aminotransferase (cAspAT) is a ubiquitous enzyme that displays liver-specific hormonal regulation. In the hepatoma cell line Fao, both the activity and the mRNA level of cAspAT are increased by glucocorticoids. This effect is potentiated by cAMP and inhibited by insulin. Using in vivo run-on experiments, we showed that these effectors act at the transcriptional level. A cAspAT gene fragment containing 2405 bp of the promoter was sequenced. Deletion fragments of this promoter were inserted upstream of the CAT gene, and the regulation of their activity was assayed following transfection in Fao cells. Stable transfection experiments established that the construct including the entire 2.405-kb fragment undergoes positive regulation by glucocorticoids and cAMP and negative regulation by insulin similar to the regulation of the endogenous gene. A physical separation of the positive and negative control elements is suggested by the fact that cAMP acted on the -682/-26-bp fragment (a 2-fold increase of the stimulation by dexamethasone), whereas the negative regulation by insulin (50% of the stimulation by dexamethasone) required the -1983/-1718-bp fragment. Both regions were required for maximal glucocorticoid activity (6-9-fold increase of CAT activity). We conclude that at least two regulatory regions, a proximal and a distal one, are required for full hormonal regulation of the cAspAT gene.

[Treatment of venous thrombosis with low molecular weight heparin and fluindione]. / Traitement des thromboses veineuses par héparine de bas poids moléculaire et fluindione.

Thirty-one consecutive patients with deep vein thrombosis were treated with Fraxiparine, a low molecular weight heparin, and fluindione, an oral anticoagulant prescribed at an early stage. Despite the weight/biological effectiveness ratio, the dose of Fraxiparine had to be adjusted in 46 percent of the patients to remain within the therapeutic range selected (0.5 to 1 antiXa/ml units). The early administration of fluindione reduced the duration of heparin therapy to 5.75 days. Using a prescription guide on days 2 and 4 might improve the safety of the fluindione induction.

Hormonal discrimination among transcription start sites of aspartate aminotransferase.

The promoter of the gene coding for the rat cytosolic aspartate aminotransferase was cloned from a Charon 4A genomic library. We have sequenced a 1.1-kilobase PstI-PstI fragment which contains the first exon of the gene, the beginning of the first intron and 682 base pairs of the 5' regulatory region (+1 being the A of the first ATG codon), which exhibits promoter activity. The promoter region is G + C rich, does not include any TATA-like element, but has 4 putative Sp1-binding sites and 6 regularly spaced CCAAT boxes. The promoter activity of the 5' regulatory region, as well as its sensitivity to glucocorticoids, were assessed by transient gene expression assays after fusion to the chloramphenicol acetyltransferase gene in the hepatoma cell lines HepG2 and Fao. Multiple transcription start sites were found on the gene over a short distance (55 base pairs), but they were differentially regulated by glucocorticoids as determined by both primer extension analysis and S1 mapping. In particular, transcription from 2 start sites was increased 15- to 18-fold, whereas transcription from the 3 other ones was increased 3-fold. In addition, three new start sites, below the detection limit in control cells, were highly induced. Therefore, a hormonal regulatory element can discriminate among closely related transcription start sites.

[Sheathing periostitis and Crohn's disease]. / Périostose engainante et maladie de Crohn.

Periostitis is an uncommon extradigestive lesion in Crohn's disease. We report two cases. The first patient was a young man presenting with moderate digestive symptoms, intense bone pain and high fever simulating osteomyelitis. The second case was more similar to those previously reported in the literature as the periostal new bone formation occurred in a woman already treated for Crohn's disease. These observations show the importance for clinicians to be aware of the association of periostitis and Crohn's disease, especially as corticotherapy is susceptible to improve bone pain as well as digestive symptoms.