[Indirect and mixed mechanisms of action in toxic myopathies]. / Mécanismes d'action indirects et mixtes mis en jeu dans les myopathies toxiques.

Toxic myopathies are a group of pathologies characterized by a structural and/or functional disturbance of muscles induced by an exogenous agent. The most frequent are those induced by drugs used in clinical practice. Illegal drugs, pesticides, solvents, metals and even physical and gaseous agents can cause this kind of disease and exert toxicity on muscle tissues. Some toxins from animals, plants or micro-organisms are potent myotoxic agents, which can lead to fatal complications. Respiratory arrest and rhabdomyolysis are often referred to as the ultimate complications of these pathologies. Several mechanisms of action can be triggered. Muscles may represent a direct target for exogenous agents by acting on the myocyte components or indirect target by inducing functional disorders. These disorders are triggered by neuromuscular interferences (organophosphates, antipsychotics, curares, etc.) and endocrine (glucocorticoids and ethyl alcohol), immune (d-penicillamine and statins) and hydroelectrolytic system dysfunctions (diuretics, laxatives and toluene). Direct and indirect effects can be induced by the same toxic agent, such as carbon monoxide, glucocorticoids, ethyl alcohol and some toxins from snake venoms.

[Direct mechanism of action in toxic myopathies]. / Mécanismes d'action directs mis en jeu dans les myopathies toxiques.

Toxic myopathies are a large group of disorders generated by surrounding agents and characterized by structural and/or functional disturbances of muscles. The most recurrent are those induced by commonly used medications. Illicit drugs, environmental toxins from animals, vegetables, or produced by micro-organisms as well as chemical products commonly used are significant causes of such disorders. The muscle toxicity results from multiple mechanisms at different biological levels. Many agents can induce myotoxicity through a direct mechanism in which statins, glucocorticoids and ethyl alcohol are the most representative. Diverse mechanisms were highlighted as interaction with macromolecules and induction of metabolic and cellular dysfunctions. Muscle damage can be related to amphiphilic properties of some drugs (chloroquine, hydroxychloroquine, etc.) leading to specific lysosomal disruptions and autophagic dysfunctions. Some agents affect the whole muscle fiber by inducing oxidative stress (ethyl alcohol and some statins) or triggering cell death pathways (apoptosis or necrosis) resulting in extensive alterations. More studies on these mechanisms are needed. They would allow a better knowledge of the intracellular mediators involved in these pathologies in order to develop targeted therapies of high efficiency.

[Erythermalgia and type 1 diabetes: diagnosis and management issues. A case report]. / Erythermalgie et diabète de type 1: difficultés diagnostiques et problèmes de prise en charge thérapeutique. A propos d'un cas.

Erythermalgia is a very rare acrosyndrome mainly characterized by lower limbs pain. It is either primitive or secondary. Concomittence of erythermalgia and diabetes is a coincidence and since the latter induces neuropathic and vascular lesions, erythermalgia is then considered as a consequence. We report the case of a young type 1 diabetic patient who presents with severe form of erythermalgia. Through this case report and a review of the literature, we shall explain the etiopathogenic mecanisms involved in erythermalgia in a diabetic patient and highlight the diagnosis and management challenges.

Clinical features and bleeding risk factors of angiodysplasia lesions in a Tunisian population.

INTRODUCTION: Gastrointestinal angiodysplasia (GIAD) is the most common vascular anomaly in the gastrointestinal (GI) tract, yet little is known about the factors favoring their bleeding. Our study aim was to determine the characteristics of patients with GIAD lesions in a Tunisian population and identify the risk factors of bleeding. PATIENTS AND METHODS: A retrospective study was carried out from January 2010 to February 2020 at a tertiary care medical center in Tunisia. Clinical and endoscopic data were collected from each patient's medical reports. We divided the patients into two groups: group A, patients with symptomatic GIAD; and group B, patients with incidental lesions. Group A was subsequently divided into two subgroups, according to the presence or absence of recurrent bleeding. The groups were compared by clinical, laboratory, and endoscopic features. RESULTS: GIAD was diagnosed in 114 patients, with a mean age of 70 ±â€¯13.3 years. GIAD lesions were mainly located in the colon (n = 72, 63%). Fifty-four patients (47%) presented with GIAD-related bleeding. The bleeding diagnosis was made during endoscopic procedures by visualizing active bleeding and the stigmata of recent hemorrhage in 10 (18.5%) and 12 (22.2%) cases, respectively. Most of the patients were treated by argon plasma coagulation (93%). Predictive factors of bleeding were age > 75 years, number of lesions >10, chronic kidney disease, diabetes mellitus, and coronary artery disease (p: 0.008; 0.002; 0.016; 0.048; and 0.039, respectively). CONCLUSION: Knowledge of the predictive factors of bleeding aids endoscopists in the decision-making process in cases of angiodysplasia.

Prediction of superconductivity in Li, K, Ca, and Sr-intercalated blue phosphorene bilayer using first-principle calculations.

Blue phosphorene is an interesting two-dimensional (2D) material, which has attracted the attention of researchers, due to its affluent physical and chemical properties. In recent years, it was discovered that the intercalation of alkali metals and alkaline earth metals in 2D materials may lead to conventional Bardeen-Cooper-Schrieffer (BCS) superconductivity. In this work, the electronic structure, phonon dispersion, Eliashberg spectral function, electron-phonon coupling (EPC), and the critical temperature of blue phosphorene bilayer intercalated by alkali metals (Li, and K) and alkaline earth metals (Ca, and Sr) for both AB and AC stacking orders are studied using the density functional theory and the density functional perturbation theory, within the generalized gradient approximation with van der Waals correction. The present work shows that the blue phosphorene bilayer is dynamically stable in AB stacking for Li and AC stacking for K, Ca, and Sr, and after intercalation, it transforms from a semiconductor to a metal owing to charge transfer between intercalated atoms and phosphorene. Furthermore, the EPC constant and the critical temperature are higher than those of 2D BCS-type superconductors. They are about 3 and 24.61 K respectively for K-intercalated blue phosphorene bilayer. Thus, our results suggest that blue phosphorene is a good candidate for a superconductor.

[The 869C>T And 915G>C Polymorphisms of TGF-ß1 and Type 1 Diabetic Retinopathy in the Algerian Population]. / Polymorphismes 869C> T et 915 G>C du TGF-ß1 dans la rétinopathie du diabète de type 1 chez la population algérienne.

INTRODUCTION: Diabetic retinopathy (DR) is characterized by chronic low-grade inflammation in which the effects of genetic factors is well established. The objective of our study is to explore an association of the 869C>T and 915G>C polymorphisms of the TGF-ß1 gene with type 1 diabetic retinopathy in the Algerian population. PATIENTS AND METHODS: A case-control study was carried out in which the SNPs 869C>T and 915G>C of the TGF-ß1 gene were analysed by the PCR-SSP technique. We compared the distribution of allelic and genotypic frequencies between patients with and without retinopathy and looked for an association between these polymorphisms and certain clinical characteristics of and risk factors for diabetic retinopathy. RESULTS: A significant increase in the frequencies of the C allele (P=0.03) and GG genotype (P=0.007) of the 915 G>C polymorphism were found, respectively, in patients without and with retinopathy. However, no significant difference was found for allelic and genotypic frequencies of the 869C>T SNP (all P>0.05) or associations between genotypes and clinical characteristics or risk factors for DR. CONCLUSION: Our preliminary results suggest that the C allele of the 915 G>C polymorphism of TGF-ß1 is protective against type 1 diabetic retinopathy in the Algerian population, while the GG genotype could confer susceptibility to it.

[Prevalence of extra-hepatic manifestations in infection with hepatitis C virus: study of 140 cases]. / Prévalence des manifestations extra hépatiques au cours des infections par le virus de l'hépatite C : etude de 140 cas

AIM: To determine the extrahepatic manifestations (EHM) in chronic hepatitis C and to correlate signs with age, sex, degree of fibrosis and genotype of hepatitis C virus. METHODS: One hundred forty cases of chronic infection by hepatitis C virus were investigated in a period of 10 years. By interrogation, clinical examination and laboratory tests, the EHM were determined. Correlations with age, sex, viral genotype and degree of fibrosis were determined by the chi2 test. RESULTS: Mean age of our patients was 59 years (16-85 years). 74% were women. The genotype 1b was found in 75% of cases. The clinical EHM were found in 62% of cases: buccal dryness in 17.1% of cases, arthralgias in 33% of cases and fatigue in 65% of cases. 25% of patients had at least one biological EHM associated with chronic hepatitis C: proteinuria in 3 cases, cryoglobulinemia in 4 cases, dysthyroidism in 8 cases and more frequently a positive immunologie test. During the follow-up, we found one case of breast cancer, one case of rectal cancer, 2 cases of MALT lymphoma and one case pf splenic lymphoma. A positive correlation was found between the prevalence of EHM in chronic hepatitis C and the female sex. A degree of fibrosis ³ 2 in METAVIR classification was significantly associated with more important frequency of EHM. CONCLUSION: EHM should be screened systematically in chronic infection with HCV. Pathogenic mechanisms in a B lymph node proliferation or diabetes and outcome of these abnormalities under antiviral therapy should be further investigated.

[T-786C endothelial nitric oxide gene polymorphism and type 1 diabetic retinopathy in the Algerian population]. / Polymorphisme T-786C de l'eNOS dans la rétinopathie du diabète de type 1 chez la population algérienne.

INTRODUCTION: Diabetic retinopathy (DR) results from interactions between genetic and environmental factors. We were interested in the endothelial nitric oxide gene (eNOS), given the involvement of this enzyme in functional alterations in the retinal microvasculature in diabetes. The goal of our study was to assess the association of T-786C endothelial nitric oxide synthase (eNOS) gene polymorphism with diabetic retinopathy in the Algerian population. PATIENTS AND METHODS: Our study enrolled 110 patients with and without DR. All subjects were genotyped for the T786C eNOS polymorphism using the PCR-RFLP method. We also investigated the association between this polymorphism and certain clinical and laboratory characteristics of patients with DR. RESULTS: A significant increase in the frequency of the CC genotype is noted in subjects without DR (P=0.03). We also report a significant increase in the frequencies of the TT+TC genotypes in individuals with DR (P=0.03). However, the association between the different genotypes and clinical or laboratory profiles in patients with DR reveals that the NO level is lower in subjects carrying the TT genotype (P=0.039). CONCLUSION: Our preliminary results suggest that the CC genotype could confer protection from type 1 diabetic retinopathy in the Algerian population, while the T allele seems to confer susceptibility.

Prevalence and risk factors of Helicobacter pylori infection in Tunisian children: 1055 children in Cap-Bon (northeastern Tunisia).

PURPOSE: The aim of this study was to determine the prevalence of Helicobacter pylori infection in a population of schoolchildren six years of age and to identify the risk factors that predispose children to such infection. PATIENTS AND METHODS: A total of 1055 first-grade primary-school pupils were included. Socioeconomic factors, eating habits, gastrointestinal complaints and family history of peptic ulcer or gastric cancer were recorded with a questionnaire. Serum samples were collected to determine H. pylori infection status using ELISA for IgG antibodies. RESULTS: The prevalence of H. pylori infection was 51.4%. On univariate analysis, risk factors for H. pylori infection were household-crowding, lower socioeconomic status, late weaning from bottlefeeding (more than 18 months), bed-sharing and cup-sharing. Symptoms related to infection were abdominal pain and vomiting. On multivariate analysis, household-crowding, late bottle-weaning, bed-sharing and abdominal pain were the only variables that remained strongly associated with H. pylori infection. CONCLUSION: The high prevalence of H. pylori infection in Tunisian children is associated with poor living conditions.

Clinical variables and ethnicity may influenced by polymorphism of CAT -262C/T and MnSOD 47C/T antioxidant enzymes in Algerian type1 diabetes without complications.

The latest studies in Algeria show that the frequency of type 1 diabetes (T1D) without complications is lower than that with complications and represents a significant burden in terms of cost and treatment. For this reason, we are interested in uncomplicated type1 diabetes and risk factors that are related to polymorphisms of antioxidant enzymes in order to prevent its complications. A total of 260 blood samples of young Algerian adults were examined. The genotypic analysis of Catalase gene (CAT -262C/T, rs1001179) and the superoxide dismutase gene (MnSOD 47C/T, rs4880) was performed by real-time PCR using TaqMan technology. The genotypic distribution of the CAT -262C/T promoter gene's polymorphism showed a significant difference between control and T1D patients for the CC genotype (p = 0.009; OR = 0.30) and for the T allele (p = 0.002; OR = 2.82). In addition, the genotypic distribution of the MnSOD 47C/T gene showed an association with T1D for the CT genotype (p = 0.040; OR = 2.37). Our results revealed that polymorphisms of CAT and MnSOD may be associated with physiopathology causing the onset of T1D. Our data, suggest that the genotypic frequencies of these SNPs appear to be influenced by clinical variables and by the Arab-Berber ethnic origin of the Algerian population.

Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo.

GLE1 mutations cause lethal congenital contracture syndrome 1 (LCCS1), a severe autosomal recessive fetal motor neuron disease, and more recently have been associated with amyotrophic lateral sclerosis (ALS). The gene encodes a highly conserved protein with an essential role in mRNA export. The mechanism linking Gle1 function to motor neuron degeneration in humans has not been elucidated, but increasing evidence implicates abnormal RNA processing as a key event in the pathogenesis of several motor neuron diseases. Homozygous gle1(-/-) mutant zebrafish display various aspects of LCCS, showing severe developmental abnormalities including motor neuron arborization defects and embryonic lethality. A previous gene expression study on spinal cord from LCCS fetuses indicated that oligodendrocyte dysfunction may be an important factor in LCCS. We therefore set out to investigate the development of myelinating glia in gle1(-/-) mutant zebrafish embryos. While expression of myelin basic protein (mbp) in hindbrain oligodendrocytes appeared relatively normal, our studies revealed a prominent defect in Schwann cell precursor proliferation and differentiation in the posterior lateral line nerve. Other genes mutated in LCCS have important roles in Schwann cell development, thereby suggesting that Schwann cell deficits may be a common factor in LCCS pathogenesis. These findings illustrate the potential importance of glial cells such as myelinating Schwann cells in motor neuron diseases linked to RNA processing defects.

Non-primate EIAV-based lentiviral vectors as gene delivery system for motor neuron diseases.

Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are neurodegenerative diseases, which cause progressive paralysis and premature death in affected adults and children. The treatment rational for these diseases is to halt or delay the degeneration of motor neurons but to date there are no effective drugs. This may however change with recent advances in gene therapy using lentiviral vectors. These vectors can transfer genes to motor neurons with high efficiency and give long term expression. One of these vector systems, based on the equine infectious anaemia virus (EIAV), can insert genes into the cells of the central nervous system after remote delivery including delivery into the muscle by exploiting retrograde transport pathways. This opens up the exciting possibility of rescuing the denervation of key muscle groups in patients by simple injections of these neurotropic lentiviral vectors into the muscle. This review will describe the general features of lentiviral vectors derived from the EIAV. It will then describe some key examples of gene transfer and genetic correction in animal models of motor neuron disease. The prospects for the clinical evaluation of lentiviral vectors for the treatment of human motor neuron disease will be outlined.

Lentiviral vectors for the treatment of neurodegenerative diseases.

A number of potential gene therapy applications in the adult nervous system include neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. During the last five years, lentiviral vectors have developed into extremely efficient gene transfer vehicles to the nervous system, revealing a wide range of possibilities for the treatment or such disorders. This review describes the most important and recent advances in the development of lentiviral vectors as well as the demonstration of proof-of-principle in animal models of human neurodegenerative diseases.

Compensatory mechanism of motor defect in SOD1 transgenic mice by overactivation of striatal cholinergic neurons.

Expression of a mutant superoxide dismutase 1 (SOD1) gene in transgenic mice induces a gradual degeneration of cholinergic motor neurons in the spinal cord, causing progressive muscle weakness and hindlimb paralysis. Transgenic mice over-expressing the human SOD1 gene containing a Gly-->Ala substitution at position 93 (G93A) were employed to explore the effects of the SOD1 mutation on choline acetyltransferase (ChAT) expression in the striatum, and in the lumbar and cervical spinal cord. These mice showed a progressive loss of their spinal cord motor neurons, and at 130 days of age showed an up-regulation of ChAT mRNA expression in the striatum. On the other hand, ChAT mRNA decreased in cervical and lumbar motor neurons. These findings suggest that cholinergic interneurons in striatum in SOD1 transgenic mice are over-activated in an attempt to compensate for the death of spinal motor neurons.

[Detection of hepatitis C virus in the general population of Tunisia]. / Dépistage de l'hépatite virale C dans la population générale en Tunisie.

We searched for antibodies to hepatitis C in a sample of 3079 Tunisians in the suburban area of Tunis. 30 people were positive by ELISA and 22 were confirmed by immunoblotting. This result represents a prevalence of 0.71% which is close to the values reported in European countries of the Mediterranean area.

[Lightning injury of the ear]. / Fulguration d'oreille.

Three cases of auricular fulguration are described and used as a basis for a review of physical characteristics and histopathologic consequences of lightning strikes. Cases are presented and discussed in relation to these fundamental and experimental data.

[Survey on the harmfulness of listening to music with headphones]. / Enquête sur la nuisance de l'écoute de la musique au casque.

A survey conducted in 52,000 young male subjects evaluated the influence of listening to music with stereophonic headphones on perception hypacusis leading to exemption from National Service. Also investigated were noise level output from promenaders as well as temporary auditory loss two minutes after listening for one hour. Findings suggested relative innocuity of listening at moderate intensity for less than seven hours weekly. Users exceeding these optimal factors develop professional type deafness for which similar preventive measures are required. Particular mention is made of the effect of strolling listeners on vigilance and on sound pollution of industrialized countries.

[Major acoustic injuries caused by firearms]. / Les traumatismes sonores majeurs par arme à feu.

The appearance of new generations of firearms, very harmful for the hearing of the shooter, suggested the need for an updated review of data concerning detonations and their effect on hearing. Emphasis is given to the place of acoustic injuries among traumatic pressure-induced otopathies as well as the value and efficacy of current therapeutic measures.

[Gastric carcinoid tumors]. / Les tumeurs carcinoides gastriques. A propos de trois cas.

Carcinoïdeses gastric tumors represent 0.3% of the gastric tumors. We bring back 3 observations of carcinoïdeses gastric tumors whose surgical treatment was not possible that at a patient aged of 30 years. The evolution was favorable with 3 years of receding. The treatment of carcinoïdeses gastric tumors remains essentially surgical but the sporadic shapes that are most aggressive require a more vigorous therapeutic attitude.