F. Fakhfakh

New mutation c.374C>T and a putative disease‐associated haplotype within SCN1B gene in Tunisian families with febrile seizures

Background:  Febrile seizures (FSs) relatively represent the most common form of childhood seizures. FSs are not thought of as a true epileptic disease but rather as a special syndrome characterized by its provoking factor (fever) and a typical range of 3 months to 5 years. Although specific genes affecting the majority of FS cases have not been identified yet, several genetic loci for FSs have been reported recently. The aim of this report is to search for the gene responsible for FSs in six affected Tunisian families.

Quercetin attenuates lambda cyhalothrin-induced reproductive toxicity in male rats.

The aim of this study was to evaluate the possible protective effects of Quercetin (Qe) against oxidative stress induced by λ cyhalothrin (LTC) in reproductive system. Thirty‐two male rats were divided into four groups. First group was allocated as the control group. Second group was given a Qe alone while the third group received a LTC alone. Animals in the fourth group were given a Qe with LTC. Caudae epididymis was removed for sperm analysis. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione‐S‐transferase (GST), and reduced glutathione (GSH) were determined in the testis. Additionally, the different histopathologic changes were observed in the testis of animals. LTC exposure significantly increased the abnormal morphology and LPO. On the contrary, sperm motility, viability and count, levels of GSH, and activities of SOD, CAT, GPx, and GST were significantly decreased compared to controls. Qe with LTC offset the decrease in functional sperm parameters, antioxidants enzymatic activities, and nonenzymatic antioxidant levels when compared with LTC‐treated rats. Furthermore, LTC showed irregular seminiferous tubules containing only Sertoli cells and Qe with LTC caused regular seminiferous tubules showing spermatogenesis at level of spermatocytes. We conclude that LTC‐induced oxidative stress and functional sperm parameters in male rats, and dietary of Qe attenuates the reproductive toxicity of LTC to restore the antioxidant system and sperm parameters in male rats.

Protective role of caffeic acid on lambda cyhalothrin-induced changes in sperm characteristics and testicular oxidative damage in rats

The synthetic pyrethroids are expected to cause deleterious effects on most of the organs and especially on the male reproductive system. The current study was performed to assess the adverse effect of lambda cyhalothrin (LC) on reproductive organs and fertility in male rats and to evaluate the protective role of caffeic acid phenethyl ester (CAPE) in alleviating the detrimental effect of LC on male fertility. A total of 48 male rats were divided into 4 groups (12 rats each): control group received distilled water ad libitum and 1 ml of vehicle solution given intraperitoneally (i.p.); CAPE-treated group received a single i.p. dose of CAPE (10 μmol kg−1 day−1); LC-treated group received 668 ppm of LC through drinking water; and CAPE + LC-treated group received an i.p. injection of CAPE (10 μmol kg−1 day−1) 12 h before the LC administration. The experiment was conducted for 10 consecutive weeks. LC caused a significant increase in testicular malondialdehyde, catalase, superoxide dismutase, glutathione-S-transferase activities, and sperm abnormalities and a significant reduction in testicular glutathione concentration, sperm count, sperm motility, and a live sperm percentage. Conversely, treatment with CAPE improved the reduction in the sperm characteristics, LC-induced oxidative damage of testes and the testicular histopathological alterations. Results indicate that LC exerts significant harmful effects on the male reproductive system and that CAPE reduced the deleterious effects of LC on male fertility.

Genetic screening of two Tunisian families with generalized epilepsy with febrile seizures plus

Background and purpose:  Febrile Seizure can be associated with heterogeneous epilepsy phenotypes regrouped in a syndrome called generalized epilepsy with febrile seizures plus (GEFS+). The aim of this report is to search for the gene responsible for GEFS+ in two affected Tunisian families.

Exposure to lambda-cyhalothrin, a synthetic pyrethroid, increases reactive oxygen species production and induces genotoxicity in rat peripheral blood

Lambda-cyhalothrin (LTC) is a synthetic pyrethroid with a broad spectrum of insecticidal and acaricidal activities used to control a wide range of insect pests in a variety of applications. However, there is little known about its adverse effects, in particular those related to its genotoxicity in humans. To elucidate the genotoxicity mechanisms of LTC, the micronuclei (MN) frequencies, the levels of reactive oxygen species (ROS), erythrocyte osmotic fragility, nitrite (NO) formation, protein carbonyl (PCO) levels and malondialdehyde (MDA) production were evaluated for a period of 7, 14 and 21 days. Our results show that exposure rat to LTC (1/10DL50 = 6.23 mg/kg) for a period of 7, 14 and 21 days induced a noticeable genotoxic effect in rat peripheral blood evidenced by a significant increase in the frequency of MN only at day 21 of treatment. Significant differences between the two groups were observed in erythrocyte osmotic fragility. Further, a significant (p < 0.01) increase in ROS contents, NO formation, PCO levels and lipid peroxidation in erythrocytes were observed at different times of treatments, suggesting the implication of oxidative stress in its toxicity. These results confirm the genotoxic and the pro-oxidant effects of LTC in rat peripheral blood.

Caffeic acid and quercetin protect erythrocytes against the oxidative stress and the genotoxic effects of lambda-cyhalothrin in vitro

Lambda-cyhalothrin (LTC) is a synthetic pyrethroid with a broad spectrum of insecticidal and acaricidal activities used to control wide range of insect pests in a variety of applications. The aim of this study was to examine (i) the potency of LTC to induce oxidative stress response in rat erythrocytes in vitro and (ii) the role of caffeic acid (20 μM) and/or quercetin (10 μM) in preventing the cytotoxic effects. Erythrocytes were divided into four portions. The erythrocytes of the first portion were incubated for 4 h at 37°C with different concentrations (0, 50 and 100 μM) of LTC. The others portions were pretreated with caffeic acid and/or quercetin for 30 min prior to LTC incubation. Lipid peroxidation, protein oxidation, antioxidant enzyme activities and DNA damage were examined. LTC at different concentrations causes increased levels of lipid peroxidation, protein oxidation, DNA damage and decreased antioxidant enzyme activities. Combined caffeic acid and quercetin pretreatments significantly reduced the levels of lipid peroxidation markers, that is thiobarbituric acid reactive substance (TBARS), protein carbonyls (PCO) and decreased DNA damage in LTC portion. Further, combined caffeic acid and quercetin pretreatment maintain antioxidant enzyme activities and glutathione content near to normal values. These results suggest that LTC exerts its toxic effect by increasing lipid peroxidation, altering the antioxidant enzyme activities and DNA damage. Caffeic acid and quercetin pretreatments prevent the toxic effects of LTC, suggesting their role as a potential antioxidant.

Chromosomal instability associated with a novel BLM frameshift mutation (c.1980‐1982delAA) in two unrelated Tunisian families with Bloom syndrome

The Bloom syndrome (BS) is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility and cancer risk. BS cells show genomic instability, particularly an hyper exchange between the sister chromatids due to a defective processing of the DNA replication intermediates. It is caused by mutations in the BLM gene which encodes a member of the RecQ family of DExH box DNA helicases. In this study, we reported cytogenetic, BLM linkage and mutational analyses for two affected Tunisian families. The Cytogenetic parameters were performed by chromosomal aberration (CA) and sister chromatid exchange (SCE) assays and results showed a significant increase in mean frequency of CA and SCE in BS cells. BLM linkage performed by microsatellite genotyping revealed homozygous haplotypes for the BS patients, evidence of linkage to BLM gene. Mutational analysis by direct DNA sequencing revealed a novel frameshift mutation (c.1980‐1982delAA) in exon 8 of BLM gene, resulting in a truncated protein (p.Lys662fsX5). The truncated protein could explain genomic instability and its related symptoms in the BS patients. The screening of this mutation is useful for BS diagnosis confirmation in Tunisian families.

Variabilité génétique des femmes XY : expérience du laboratoire de génétique moléculaire humaine de Sfax, Tunisie

LH exprimé dans les cellules de Leydig ; d’expression phénotypique limitée aux garçons. Cas rapporté.– Nous rapportons le cas de I.A., un garçon âgé de deux ans et sept mois. L’examen clinique retrouve un poids et une taille supérieurs à +3 D. Un stade de TANNER : G3P3 avec une verge supérieure à +2DS. L’âge osseux est de sept ans et le bilan hormonal e révèle un taux élevé de testostérone et un taux bas de FSH LH. Le test de LHRH et l’IRM hypothalamohypophysaire sont en faveur de l’origine périphérique. Les autres étiologies de l’origine périphérique ont été éliminées. L’étude génétique est en cours. Un traitement par kétoconazol a été démarré chez lui. Discussion.– La testotoxicose résulte d’une mutation activatrice du récepteur de LH chez le garçon, se manifestant par une grande taille, un agrandissement de la verge, une pilosité pubienne, et un âge osseux avancé compromettant la taille finale. Le kétoconazol est un moyen thérapeutique efficace à long terme sur le pronostic de la taille finale mais reste limité par ses effets indésirable. L’inhibiteur de l’aromatase seul ou en association aux antiandrogéniques s’est avéré efficace, mais son prix reste relativement cher. Le traitement de la testotoxicose est souvent compliqué par l’apparition d’une puberté précoce centrale nécessitant un traitement par agonistes de LHRH.