Rim Atheymen

Relation entre les concentrations plasmatiques d’acide valproïque et la survenue d’une hépatotoxicité

INTRODUCTION Valproic acid (VPA) is an anticonvulsivant drug widely prescribed in the treatment of many forms of generalized epilepsy. In literature, the incidence of liver damage induced by AVP is 0.01%. It is potentialized by the combination therapy (phenobarbital, carbamazepine). Severe hepatotoxicity is rare and appears to be independent of dose and to cause a high mortality. METHODS The aim of our study was to evaluate the relationship between plasma concentrations of AVP and the occurrence of side effects especially hepatotoxicity in patients receiving high doses of AVP. RESULTS In this period, 425 plasmatic AVP monitoring were carried out in our laboratory. From 128 patients treated by high doses of AVP, only 73 were included in this study. Our work showed that adverse effects in epileptics under high doses of AVP was related to the association of the AVP with other antiepileptic in particular carbamazépine, phenobarbital and benzodiazepines rather than supra-therapeutic plasmatic concentrations of AVP. The association of AVP to major antiepileptics (carbamazépine and or phenobarbital) does not seem to generate an increase in the plasmatic concentration of AVP, which was not associated with a greater risque of adverse effects. CONCLUSION Consequently, clinical signs of liver toxicity may be present in AVP concentrations generally considered in the therapeutic range especially when used in high doses and or combined with antiepileptic drugs like phenobarbital or carbamazepine.

Antioxidant and androgenic effects of dietary ginger on reproductive function of male diabetic rats

Abstract This study evaluated the antioxidant and androgenic properties of ginger roots on the reproductive function of male diabetic rats. Animals were divided into three groups; the control (Control), diabetic (Diab) and diabetic fed with dietary ginger for 30 d (Diab + Z). Thereafter, blood samples were collected and reproductive organs (testis, epididymis, prostate and seminal vesicle) were removed for determination of sperm parameters, malondialdehyde (MDA) level, glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and aspartate and lactate aminotransferase (AST and ALT) activities. Dietary ginger decreased blood glucose and MDA level, increased reproductive organ weights and testosterone level, improved semen quantity and motility, and ameliorated the SOD, CAT and GPx activities as well as testis AST, ALT, LDH and ALP activities. Intake of ginger roots improves the antioxidant and androgenic reproductive function of male diabetic rats in addition to its antidiabetic property.

Autoimmune hepatitis as an adverse effect of long-term methotrexate therapy

Methotrexate (MTX) is one of the most commonly used medicines in the treatment of psoriatic arthritis. The drug can produce steatosis and cirrhosis. Autoimmune hepatitis is a rare and serious adverse effect. We describe the case of a 53-year-old woman who developed autoimmune hepatitis after a long-term use of MTX for psoriatic arthritis. Hepatitis was completely resolved 4 months after stopping this drug. The pathophysiologic mechanisms of a drug-induced autoimmunity are unclear and complex. This report confirms the need to monitor liver enzymes carefully in patients using long-term treatment with MTX for psoriasis or rheumatoid arthritis.

Ageusia as a side effect of clopidogrel treatment

Clopidogrel is prescribed in cardiac and extracardiac vascular diseases. It is generally well tolerated; however, few cases of taste disorders have been reported. We present a case of clopidogrel-induced ageusia notified in Sfax pharmacovigilance center on March 13, 2009. A 46-year-old patient developed ageusia with decreased appetite five weeks after starting clopidogrel. Other etiologies including ear nose throat (ENT) examination were ruled out. Five months after reduction of clopidogrel dose, ageusia partially decreased. Clopidogrel was strongly suspected as a causal drug. According to the French imputation method, score of imputability was considered as plausible (C2S2) I2. Physiopathology of this side effect is not yet understood. However, it seems to be a reversible and dose-related event. Although it is not life-threatening, loss of taste can have significant effect on the quality of life of patients.

Globularia alypum methanolic extract improves burn wound healing process and inflammation in rats and possesses antibacterial and antioxidant activities

Burns are known as one of the most common and destructive forms of injury with a vast spectrum of consequences. Despite the discovery of various antibacterial and antiseptic agents, burn wound healing still has remained a challenge to modern medicine. Plants have been considered as potential agents for prevention and treatment of disorders in recent years. Globularia alypum L. (GA) is widely used in folk medicine against skin diseases and abscesses, however there is no scientific evidence justifying its use. This study aimed to evaluate the wound healing and anti-inflammatory effect, the antibacterial and antioxidant activities, as well as the chemical compositions of GA methanolic extract (GAME). Chemical compounds of GAME were examined by GC-MS. Wound healing effect was assessed by second-degree burn wounds in rats, anti-inflammatory activity was studied by carrageenan-induced rat paw edema, antioxidant activity was estimated by the DPPH, reducing power and β-carotene tests and antimicrobial activity was tested against 6 bacteria. A total of 17 compounds were identified. GAME-treated rats showed an improvement in healing process and carrageenan-induced hind paws edema as assessed by histological and biochemical investigations, compared to the control. A significant antioxidant and antibacterial activities were also observed in GAME-treated rats. GAME revealed a burn wound healing activity probably due to the anti-inflammatory, antimicrobial and antioxidant activities of its phytochemical contents. Thus, this study confirms its traditional use, however further more precise studies are needed for future clinical application.

Influence of age and co-medication on the steady-state pharmacokinetics of valproic acid in Tunisian patients with epilepsy

AIM Valproic acid (VPA) is a widely prescribed broad-spectrum antiepileptic drug. However, the use of VPA is complicated in clinical practice by its remarkably wide variability of pharmacokinetics. The objective of this study was to investigate the effects of demographic factors and associated therapies on steady-state plasma VPA concentrations in patients with epilepsy. METHODS This retrospective cohort study was carried out using the routine therapeutic drug monitoring (TDM) database. Stepwise logistic regression analysis was used to compare serum VPA levels in 78 epilepsy patients treated with VPA in association with at least one other drug that could have interacted with CYP2C9, CYP2C19 or UGT enzymes. RESULTS The frequency of subtherapeutic serum VPA levels was significantly increased with younger age (P<0.02), the number of co-medications (P<0.007) and use of enzyme-inducing co-medications (P<0.02). No significant correlations between VPA dose and trough plasma concentrations were found, as the latter did not increase in proportion to the dose. CONCLUSION Routine monitoring of VPA serum levels would be extremely useful in epilepsy patients in the pediatric age group and in those who require associated enzyme-inducing medications.

Oxidative Stress in Tunisian Patients With Acute Lymphoblastic Leukemia and Its Involvement in Leukemic Relapse

The aim of the present study was to evaluate in patients with acute lymphoblastic leukemia (ALL), the oxidative status and antioxidant defense and its involvement in the relapse of ALL. The plasmatic levels of malondialdehyde, advanced oxidation of protein products and reduced glutathione (GSH), and the plasmatic activities of catalase, superoxide dismutase (SOD), and glutathione peroxidase were determined in 34 patients who were newly diagnosed with ALL and compared with 92 healthy individuals. The plasmatic concentrations of malondialdehyde and advanced oxidation of protein products were higher in ALL patients than in controls and increased during chemotherapy. A decrease in glutathione peroxidase activity and an increase in catalase and SOD activities and GSH plasma levels were observed in ALL patients, as compared with sex-matched controls. Moreover, SOD activity and GSH levels were significantly correlated with the relapse of ALL patients. These data suggest the involvement of oxidative stress in acute lymphoid leukemias and leukemic relapse.

Caffeine ingestion does not affect afternoon muscle power and fatigue during the Wingate test in elite judo players

The purpose of the present study was to evaluate the effect of caffeine ingestion on elite judo players’ mood states, simple reaction time, and muscle power during the Wingate test in the afternoon. Ten elite judo players (age: 21.08 ± 1.16 years, body mass: 83.75 ± 20.2 kg, height: 1.76 ± 0.07 m) took part in this study. The performance variables were measured during two test sessions scheduled at 17:00 h, after placebo or caffeine (5 mg/k) ingestion. The results revealed an increase in anxiety and vigour (p < 0.05) and a reduction in simple reaction time (p < 0.005) following caffeine ingestion. However, muscle power and fatigue during the Wingate test were unaffected. It is concluded that afternoon caffeine ingestion has no ergogenic effect on anaerobic performance.

Effets indésirables de la sulfasalazine : discussion de leur mécanisme et du rôle de la composante sulfamidée

Sulfasalazine is widely used in the treatment of chronic inflammatory bowel disease (IBD) and certain rheumatic diseases. However, its use is associated with a high rate of adverse effects (AEs) which can be cutaneous, hematological, renal, hepatic, gastrointestinal or neurological. The aim of our study was to collect all cases of AEs suspected to be associated with the use of sulfasalazine in patients hospitalized in the department of Gastroenterology from the Hospital Hedi Chaker of Sfax (Tunisia) for a period of 5 years and to search the incriminated fraction (sulfonamide or salicylate). Our study population included 69 patients who received sulfasalazine for the treatment of IBD. We collected, in 23 patients (33%), 25 AEs suspected to be related to sulfasalazine. Cutaneous and hematological reactions are the most common. The subsequent administration of mesalazine was performed in 15 patients. It was well tolerated in 14 patients. So we were suspecting probably the responsibility of sulfonamide fraction in these cases. The mechanism of sulfasalazine induced AEs may be toxic or immunoallergic with the possibility of a cross-reaction with the other antimicroacterial sulfonamides.