[Pharmacist's interventions on outpatient prescriptions in a university hospital drugs sales service]. / Interventions des pharmaciens sur les prescriptions ambulatoires dans le cadre de l'activité de rétrocession d'un centre hospitalier universitaire.

UNLABELLED: For public health reasons, some drugs are only available in hospital drugs sales service. This activity takes place in a specific risk context of organization, patients and/or drugs. A systematic prescription analysis by pharmacist contributes to securise treatment dispensed. The aim of this paper is to present the main drugs problems in the analysis of outpatient prescriptions and pharmaceutical interventions in three units of hospital drugs sales service belong to university hospital. METHODS: Throughout the year 2013, drug problems detected were recorded prospectively and systematically. RESULTS: Of the 22,279 prescriptions analyzed, 247 pharmaceutical interventions (1.1%) were detected including 27.6% of problems concerning the dosages, 15.4% the unconformity, 6.9% contraindications. Regarding ATC drugs classes, we found 43.7% for anti-infectives and 17.4% for antineoplatics. The overall acceptance rate is 81.8%. CONCLUSION: These results show the importance of the analysis of outpatient prescriptions before dispensing and the need to have all prescriptions, clinical and biological elements and to develop interprofessionality. The implementation of a platform for dematerialized data exchanges between professionals, including data from the pharmaceutical patient record should contribute to improving drug management of the patient.

Ubiquitin binding mediates the NF-kappaB inhibitory potential of ABIN proteins.

Deregulated nuclear factor kappaB (NF-kappaB) activation plays an important role in inflammation and tumorigenesis. ABIN proteins have been characterized as negative regulators of NF-kappaB signaling. However, their mechanism of NF-kappaB inhibition remained unclear. With the help of a yeast two-hybrid screen, we identified ABIN proteins as novel ubiquitin-interacting proteins. The minimal ubiquitin-binding domain (UBD) corresponds to the ABIN homology domain 2 (AHD2) and is highly conserved in ABIN-1, ABIN-2 and ABIN-3. Moreover, this region is also present in NF-kappaB essential modulator/IkappaB kinase gamma (NEMO/IKKgamma) and the NEMO-like protein optineurin, and is therefore termed UBD in ABIN proteins and NEMO (UBAN). Nuclear magnetic resonance studies of the UBAN domain identify it as a novel type of UBD, with the binding surface on ubiquitin being significantly different from the binding surface of other UBDs. ABIN-1 specifically binds ubiquitinated NEMO via a bipartite interaction involving its UBAN and NEMO-binding domain. Mutations in the UBAN domain led to a loss of ubiquitin binding and impaired the NF-kappaB inhibitory potential of ABINs. Taken together, these data illustrate an important role for ubiquitin binding in the negative regulation of NF-kappaB signaling by ABINs and identify UBAN as a novel UBD.

Function and regulation of tumor necrosis factor receptor type 2.

TNF is a major proinflammatory cytokine, which exerts its effects through two different receptors known as TNF-R1 and TNF-R2. Whereas TNF-R1 induced signaling pathways have been very well characterized during the past years, TNF-R2 has been much less well studied. Nevertheless, the function of TNF-R2 should not be underestimated, the more because this receptor shows a much more restricted but inducible expression. Several inflammatory diseases and cancers show upregulated levels of soluble TNF-R2 or are associated with TNF-R2 polymorphisms, implicating an important role for TNF-R2 as a therapeutic target. Here we will review the mechanisms that regulate TNF-R2 expression, as well as discuss TNF-R2 induced signal transduction and cross-talk with TNF-R1.

Lithium sensitizes tumor cells in an NF-kappa B-independent way to caspase activation and apoptosis induced by tumor necrosis factor (TNF). Evidence for a role of the TNF receptor-associated death domain protein.

We have previously shown that lithium salts can considerably increase the direct cytotoxic effect of tumor necrosis factor (TNF) on various tumor cells in vitro and in vivo. However, the underlying mechanism has remained largely unknown. Here we show that the TNF-sensitizing effect of lithium chloride (LiCl) is independent of the type of cell death, either necrosis or apoptosis. In the case of apoptosis, TNF/lithium synergism is associated with an enhanced activation of caspases and mitochondrial cytochrome c release. Sensitization to apoptosis is specific for TNF-induced apoptosis, whereas Fas-mediated or etoposide-induced apoptosis remains unaffected. LiCl also potentiates cell death induced by artificial oligomerization of a fusion protein between FKBP and the TNF receptor-associated death domain protein. TNF-induced activation of NF-kappa B-dependent gene expression is not modulated by LiCl treatment. These results indicate that LiCl enhances TNF-induced cell death in an NF-kappa B-independent way, and suggest that the TNF receptor-associated death domain protein plays a crucial role in the TNF-sensitizing effect of LiCl.

TRAF1 is a TNF inducible regulator of NF-kappaB activation.

Tumor necrosis factor receptor (TNFR)-associated factor TRAF1 was first identified as a component of the TNFR2 signalling complex. Unlike the other members of the TRAF family, TRAF1 lacks the N-terminal ring finger motif and has a tissue specific expression. Here we demonstrate that expression of TRAF1 is induced by TNF and the protein kinase C (PKC) activator PMA, but not by interleukin-1 (IL-1). TNF-induced upregulation of TRAF1 could be prevented by pretreatment of the cells with the proteasome inhibitor MG-132, whereas the PKC inhibitor Ro31-8220 was without effect. Interestingly, overexpression of TRAF1 in HEK293T completely prevented NF-kappaB activation induced by TNF, IL-1, or overexpression of TRAF2 or TRAF6. These data suggest that inducible expression of TRAF1 may serve a negative regulatory function in NF-kappaB signalling pathways.

TRAF2 plays a dual role in NF-kappaB-dependent gene activation by mediating the TNF-induced activation of p38 MAPK and IkappaB kinase pathways.

We previously demonstrated that p38 MAPK is a crucial mediator in the NF-kappaB-dependent gene activation induced by TNF. Here, we have studied the role of several TNF receptor-associated proteins and caspases in p38 MAPK activation by TNF. The latter appears to be dependent on TRAF2, but independent of FADD or caspases. Remarkably, p38 MAPK activation by TNF proceeds independently of the TRAF2-associated NF-kappaB-inducing kinase NIK, which is known to bind and activate two recently identified IkappaB kinases. These results demonstrate that two kinase pathways involved in NF-kappaB regulation, viz. NIK and p38 MAPK-mediated, diverge at the level of TRAF2.

Evaluation of a computerized program (ARSENIC) as an aid for telephone consultations in a poison center.

ARSENIC is a computerized system providing assistance for telephone consultation in poison centers. Its main characteristic is to blend the document consultation process with the case-recording procedure. It has been used in the daily routine of our poison center since 1987. To evaluate this system, 2 weeks were randomly chosen. During one, ARSENIC was used by the telephone responders; during the other week, traditional paper documents and files were used. Document search times, coding times and quality of responders were recorded by a blinded observer and analysed in total and on the basis of the training of the telephone officer (medical student, resident or toxicologist). ARSENIC decreased the document search times (3.1 +/- 2.7 min vs 3.8 +/- 2.9 min; p less than 0.05) and did not increase coding time (2.1 +/- 1.2 min vs 2.2 +/- 1.4 min; NS). For each group of telephone responders, answer quality increased with ARSENIC. More important, the answer quality of less-trained officers using ARSENIC was similar to that of trained toxicologists without ARSENIC. The quality assurance given by ARSENIC was, for us, the most important argument for computer use at telephone desks.