Molecular and biochemical characterization of Tunisian patients with glycogen storage disease type III

Glycogen storage disease type III (GSD III) is an autosomal recessive inborn error of metabolism caused by mutations in the glycogen debranching enzyme amylo-1,6-glucosidase gene, which is located on chromosome 1p21.2. GSD III is characterized by the storage of structurally abnormal glycogen, termed limit dextrin, in both skeletal and cardiac muscle and/or liver, with great variability in resultant organ dysfunction. The spectrum of AGL gene mutations in GSD III patients depends on ethnic group. The most prevalent mutations have been reported in the North African Jewish population and in an isolate such as the Faroe Islands. Here, we present the molecular and biochemical analyses of 22 Tunisian GSD III patients. Molecular analysis revealed three novel mutations: nonsense (Tyr1148X) and two deletions (3033_3036del AATT and 3216_3217del GA) and five known mutations: three nonsense (R864X, W1327X and W255X), a missense (R524H) and an acceptor splice-site mutation (IVS32-12A>G). Each mutation is associated to a specific haplotype. This is the first report of screening for mutations of AGL gene in the Tunisian population.     

L’expérimentation médicale sur les prisonniers (partie 1): les évènements historiques marquants

The exploitation of prisoners in medical research is an ancient phenomenon. However, the history of the XX^th century was marked by major events that reached the peak of horror during the second world war. Although the collective mind has remembered the outrages of the Nazi regime, the truth is that these practices were adopted by the majority of the military powers of that time, and continued after the end of the war. This history note is the first in a series that aims to review the circumstances and implications of these dark moments in the history of medical research in order to pay tribute to the countless victims who paid with their lives for «scientific progress» and to understand the reasons for current ethical considerations in biomedical experimentation on persons deprived of liberty.     

Individual and synergistic protective properties of Salvia officinalis decoction extract and sulfasalazine against ethanol-induced gastric and small bowel injuries

The present study was carried out to determine the phytochemical composition of Salvia officinalis flowers decoction extract (SOFDE) as well as its individual and/or synergistic actions with sulfasalazine against ethanol (EtOH)-induced peptic ulcer in Wistar rats. In this respect, rats were divided into six groups of eight animals each: control, EtOH, EtOH + sulfasalazine (SULF, 100 mg kg⁻¹, b.w., p.o.), mixture: MIX (SOFDE, 50 mg kg⁻¹ b.w., p.o. + SULF, 50 mg kg⁻¹, b.w., p.o.) and EtOH + two doses of SOFDE (100 and 200 mg kg⁻¹ b.w., p.o.). In vitro, the phytochemical and the antioxidant properties were determined using colorimetric analysis. HPLC-PDA/ESI-MS assay was used to identify the distinctive qualitative profile of phenolic compounds. Our results firstly indicated that SOFDE is rich in total tannins, flavonols, anthocyanins and a moderate concentration of total carotenoids. Chromatographic techniques allowed the identification of 13 phenolic compounds and the major ones are quinic acid, protocatechuic acid, gallic acid and salviolinic acid. SOFDE also exhibited an important in vitro antioxidant activity using the β-carotene bleaching method. In vivo, SOFDE and the mixture provide significant protection against ethanol-induced gastric and duodenal macroscopic and histological alterations. Also, SOFDE alone or in combination with SULF, showed a significant protection against the secretory profile disturbances, lipid peroxidation, antioxidant enzyme activities and non-enzymatic antioxidant level depletion induced by alcohol administration. Importantly, we showed that EtOH acute intoxication increased gastric and intestinal calcium, free iron, magnesium and hydrogen peroxide (H₂O₂) levels, while SOFDE/MIX treatment protected against all these intracellular mediators'' deregulation. We also showed that alcohol treatment significantly increased the C-reactive protein (CRP) and alkaline phosphatase (ALP) activities in plasma. The SOFDE and MIX treatment significantly protected against alcohol-induced inflammation. More importantly, we showed in the present work that the mixture exerted a more important effect than SOFDE and SULF each alone indicating a possible synergism between these two molecules. In conclusion, our data suggests that SOFDE and SULF exerted a potential synergistic protective effect against all the macroscopic, histological and biochemical disturbances induced by EtOH intoxication. This protection might be related in part to its antioxidant and anti-inflammatory properties as well as by negatively regulating Fenton reaction components such as H₂O₂ and free iron.

The present study was carried out to determine the phytochemical composition of Salvia officinalis flowers decoction extract (SOFDE) as well as its individual and/or synergistic actions with sulfasalazine against ethanol (EtOH)-induced peptic ulcer in Wistar rats.