Changes in differential gene expression in fibroblast cells from patients with triple A syndrome under oxidative stress.

The triple A syndrome is a rare autosomal recessive disease caused by mutations in the AAAS gene, which encodes the nucleoporin ALADIN. Recently it was shown that ALADIN plays a role in the import of different factors into the nucleus, which prevent the cell from DNA damage and consecutive cell death under oxidative stress. In order to investigate the changes in differential gene expression in ALADIN-deficient or mutated cells under oxidative stress we used fibroblast cell cultures of triple A syndrome patients and compared these to controls. Analysis of 84 genes, which are associated with oxidative stress and antioxidant defense, showed that 7 genes were significantly and differentially regulated, namely BCL2/adenovirus E1B 19kD-interacting protein 3 (BNIP3), 24-dehydrocholesterol reduc-tase (DHCR24), dual specificity phosphatase 1 (DUSP1), forkhead box M1 (FOXM1), nudix-type motif 1 (NUDT1), prostaglandin-endoperoxide synthase 2 (PTGS2), and scavenger receptor class A, member 3 (SCARA3). Whereas in control cells the expression of DHCR24, FOXM1, NUDT1, and SCARA3 was decreased after paraquat treatment, the expression did not change significantly in patient cells. However, the basal expression of SCARA3 and BNIP3 was significantly higher in patient cells than in controls whereas PTGS2 was less expressed. Furthermore, after paraquat treatment the expression of BNIP3, DUSP1, and PTGS2 was significantly increased in control cells while in patient cells the increase of DUSP1 and PTGS2 expression was significantly reduced. With this work we confirm that cells of triple A patients show an altered induction or downregulation of genes associated with oxidative stress and antioxidant defense.

[Clinicopharmacological case report (3). Drug-induced angioedema]. / Der klinisch-pharmakologische Fall (3). Medikamentös bedingtes Angioödem.

We report the case of a patient with an angioedema during therapy with enalapril and tramadol. The most likely cause of the adverse effect if the ACE-inhibitor enalapril. A rechallenge with the ACE-inhibitor is dangerous and should not be performed. Because of its potential risks, further treatment with ACE-inhibitors should be avoided in all patients with ACE-inhibitor-induced angioedema. Possible therapeutic alternatives include diuretics, beta-blocking agents, calcium antagonists and also angiotensin II receptor antagonists.

[Clinical-toxicological case (1). Dosage of N-acetylcysteine in acute paracetamol poisoning]. / Der klinisch-toxikologische Fall (1). Dosierung von N-Acetylcystein bei akuter Vergiftung mit Paracetamol.

There are currently three protocols used for the administration of N-acetylcysteine in the treatment of acute paracetamol poisoning. In the USA only the oral protocol is approved, while in Europe an intravenous protocol is used. If treatment is started within 10 h. after paracetamol ingestion, all three protocols appear to be equally effective. If treatment is started 10 to 24 h. after the ingestion, the oral protocol and the Smilkstein protocol appear to be superior to the Prescott protocol. N-acetylcysteine is effective also when started more than 15 h after the ingestion. Patients who present with liver failure after paracetamol poisoning should be treated with a prolonged course of N-acetylcysteine.

[The clinicopharmacological case (5). serotonin reuptake inhibitor and 5-HT3-receptor antagonists: are there clinically relevant interactions?]. / Der klinisch-pharmakologische Fall (5). Serotoninwiederaufnahmehemmer und 5-HT3-Rezeptor-Antagonisten: Gibt es klinisch relevante Interaktionen?

We describe a patient with chronic depression who was treated with the selective serotonin-reuptake-inhibitor sertraline. Following surgery, the patient developed severe nausea and vomiting, necessitating an efficient antiemetic treatment, possibly including the 5-HT3-receptor antagonist ondansetrone. Because both drugs, sertraline and ondansetrone, interact with the serotonin system at the synapsis, a possible interaction was discussed. Since the effect of the selective serotonin-reuptake inhibitors mainly depends on 5-HT1 and 5-HT2-receptors, a pharmacodynamic interaction between an 5-HT3-antagonist and a serotonin-reuptake-inhibitor at the synapsis leading to the relapse of depression seems to be very unlikely. There exist also no conclusive data suggesting a clinically relevant pharmacokinetic interaction between the two drugs. A treatment with ondansetrone was considered to be safe in this patient.

Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine.

AIMS: To explore drug exposure, frequency of adverse drug reactions (ADRs), types of ADRs, predisposing risk factors and ADR-related excess hospital stay in medical inpatients. METHODS: Structured data regarding patient characteristics, 'events' (symptoms, laboratory results), diagnoses (ICD10) and drug therapy were collected using a computer-supported data entry system and an interface for data retrieval from electronic patient records. ADR data were collected by 'event monitoring' to minimize possible bias by the drug monitor. The causality of each event was assessed in relation to disease(s) and drug therapy. RESULTS: The analysis included 4331 (100%) hospitalizations. The median observation period was 8 days. The median number of different drugs administered per patient and day was 6 and varied between 4 (Q1 ) and 9 (Q3 ) different drugs in 50% of all hospital days. In 41% of all hospitalizations at least one disease-unrelated event could be possibly attributed to drug therapy. Clinically relevant ADRs occurred in 11% of all hospitalizations. In 3.3% of all hospitalizations ADRs were the cause of hospital admission. The incidence of possibly ADR-related deaths was 1.4. Factors predisposing for clinically relevant ADRs were female gender and polypharmacy. ADR-related excess hospital stay accounted for 8. 6% of hospital days. CONCLUSIONS: These data demonstrate the feasibility of the developed 'event monitoring' system for quantitative analysis of ADRs in medical inpatients. With increasing numbers of recorded patients the pharmacoepidemiological database provides a valuable tool to study specific questions regarding drug efficacy and safety in hospitalized patients.