Anis Klouz

Methotrexate Side Effects: Review Article

Methotrextae (MTX) is an antifolate first developed to treat certain types of cancer. It was used at higher doses as a cancer therapy and since 1990 it is used at much lower doses to treat rheumatic diseases [1]. Side effects of MTX high dose (MTX-HD) may be life threatening, however those of various doses of oral MTX are variable because of the interindividual variability of gastrointestinal absorption of this drug. Bone marrow, gastrointestinal mucosa and hair are particularly vulnerable to the effects of MTX, secondary to their high rate of cellular turnover [2] and because MTX concentration is inversly proportianal to renal clearance [2], renal toxicity is frequent with MTX-HD.

Smoking during pregnancy and postpartum among Tunisian women

Objective. The validity of self-reported smoking in population surveys remains an important question yet to be answered. This has been of particular concern in a situation where there is a strong social pressure against pregnant and postpartum women. An associated question is what would be the value of measuring urinary cotinine concentrations in such surveys to obtain validated smoking data. Methods. Cross-sectional analysis of data on self-reported smoking and urinary cotinine among a sample of 398 pregnant women and recently pregnant, mothers of infants under the age of 2 months, who came to the Family Planning Clinic in Tunis urban area for either prenatal or newborn care. We used quantitative colorimetric urine test based on the könig reaction, in which pink-red chromophores formed from nicotine and its metabolites condensation with barbituric acid were extracted into acetate buffer. Results. The smoking prevalence among Tunisian pregnant women or mothers of newborn infants was 4%. The validity of self-reported daily smoking was relatively low. Among women reporting no smoking at the interview 16% misreported active smoking. According to urinary cotinine values, the smoking prevalence was 18.8%. Conclusions. These results substantiate the unreliability of self-report on smoking status among women in prenatal and postnatal period and have implications in clinical and education practice.

An animal model of testicular toxicity by cyclosporine: evaluation and protection

CyclosporineA (CsA) improves the survival of patients who benefited from transplantation. However, its use is generally limited by its side effects. The aim of our study was to measure, in an experimental model, the changes of the testosterone plasma levels after 21 days of CsA treatment and to explain the mechanism of this modification. After treatment, the levels of CsA, testosterone, corticosterone, transaminases were measured. The cytotoxic effect of CsA was evaluated by microscopic observation. The experimental study showed that CsA had no effect on the plasmatic levels of hepatic enzymes ‐ alanine aminotransferase, aspartate aminotransferase and gamma‐glutamyl‐transferase – because their plasma concentrations in treated rats did not differ from those of the sham group. The plasma concentration of corticosterone was not modified, the plasma level of testosterone decreased when the dose of cyclosporine was increased to 4 mg/kg/day. The photonic microscope observation showed that the number of Leydig cells was increased and the electronic microscope observation showed mitochondria alteration. The treatment by CsA and trimetazidine did not correct the alteration caused by CsA. N‐benzyl‐N’‐(2‐hydrox‐3, 4‐dimethyloxybenzyl)‐pipeazine did not protect the mitochondrial function but partially protected mitochondria structure from the deleterious effect induced by CsA. The decrease of the plasma level of testosterone induced by CsA was due to the inhibition of the mitochondrial 20–22 desmolase which blocked the formation of the testosterone precursor and the destruction of the mitochondria structure.

Allele frequency of inosine triphosphate pyrophosphatase (ITPA) and thiopurine-S-methyl transferase (TPMT) genes in the Tunisian population.

AIM The aim of this study was to determine the frequencies of TPMT and ITPA polymorphisms in Crohns disease patients of Tunisian origin and to compare them with allele frequencies previously reported in other populations of various ethnic origins. METHODS ITPA (c.94C>A and IVS2+21A>C) and TPMT (c.238G>C, c.460G>A and c.719A>G) mutations and genotypes were assessed in 208 Tunisian subjects (78 males/130 females) by polymerase chain reaction-restriction fragment length polymorphism and allele-specific-PCR methods. RESULTS Genotyping of ITPA revealed frequencies of 6% and 7.9% for c.94C>A and IVS2+21A>C, respectively. Accordingly, deficient or diminished ITPA phenotype can be predicted to concern 2.4% of Tunisians. The observed frequencies of the c. 238G>C, c.460G>A and c.719A>G TPMT polymorphisms were 0, 0.24 and 1.44%, respectively. CONCLUSION This study provides the first analysis of TPMT and ITPA mutant allele frequency in individuals of Tunisian origin. Unlike in Caucasians, TPMT*3C which harbours the c.719A>G polymorphism appears to be the most common mutant allele in Tunisians. In contrast, ITPA mutant allele frequency distribution appears to be similar to that observed in Caucasians.

Les colites médicamenteuses : revue de la littérature

Frequency of colitis induced by drugs is often under estimated. Antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDS) are usually incriminated. In this study, we classified colitis according to the main responsible drug with a focus on clinical symptomatology, physiopathology, evolution, and complications. We describe colitis due to antibiotics, NSAIDS, laxatives, vasoconstrictive agents, oestroprogestatives, chemotherapy and drugs induced microscopic colitis. The last one represents a particular case; it can be idiopathic, infectious or drugs induced. Its physiopathology is not well known and its diagnosis is based only on histologic criterion. Drug responsibility is easy to determine only for pseudomembranous colitis. In the other cases, chronology is very variable and the clinical, endoscopic and histological elements are rarely specific. Because of the large number of drugs that may induce colitis, it is necessary to search for potentially responsible drugs, especially if there is no obvious cause of the colitis.

Delayed Elimination of Methotrexate in a Patient Receiving Ciprofloxacin

High-dose methotrexate (HD-MTX) is indicated in neoplasic diseases. It is administrated at doses above 500 mg/m2 in association with alkaline hyperhydratation and folinic acid in order to interrupt the antifolinic activity of this chemotherapy.[1,2] It has several toxic side effects as mucosal ulcer, hepatitis and renal impairment.[2] This toxicity may be exacerbated by a delayed elimination of HD-MTX. Many factors may lead to the delayed elimination of HD-MTX such as renal impairment, third space fluid collections and drug-drug interactions. Non steroidal anti-inflammatory drugs (NSAIDs), probenicid, penicillin and sulfamethoxazole-trimethoprim are the most responsible of drug interactions with MTX.[3] We report herein a rare case of delayed elimination of HD-MTX associated with administration of ciprofloxacin.

Validity of self-reported smoking among women hospital staff in Tunisia

In Tunisia, smoking prevalence is high1 (55.6% males vs 5.2% females).2 However, under-reporting of smoking may occur, particularly among women from cultures where social proscriptions still exist.3 No studies on womens smoking have been published in Tunisia which have validated self-reported smoking with biomarkers such as urinary cotinine.4 We aimed to assess the validity of self-reported smoking among female staff in a Tunisian hospital. Our data were extracted from a cross-sectional study5 conducted between January and May 2005 to assess smoking behaviours of the health professional staff at Charles Nicolle Hospital in Tunis, the largest University Hospital in Tunisia. About 1120 …

Interaction médicamenteuse entre le tacrolimus et la théophylline chez un greffé rénal : à propos d’un cas

Le tacrolimus est un immunosuppresseur largement indiqué dans la greffe d’organes solides. [1] C’est un médicament métabolisé au niveau du foie par le CYP 450 3A4. De nombreuses interactions médicamenteuses sont observées avec les inducteurs et les inhibiteurs enzymatiques du système cytochrome P450, [2] entraînant dans le premier cas un risque de rejet de greffe par diminution des concentrations sanguines du tacrolimus et dans le second un risque de toxicité par augmentation de ses concentrations sanguines. Les principaux inducteurs enzymatiques interagissant avec le tacrolimus sont les anticonvulsivants, la rifampicine et les extraits de millepertuis. [2,3] Concernant les inhibiteurs enzymatiques, il s’agit essentiellement de macrolides, antiprotéases, antifongiques azolés, antagonistes calciques, amiodarone et inhibiteurs de la pompe à protons. [2,3] Nous rapportons dans ce travail un cas d’interaction médicamenteuse très rarement observé, entre le tacrolimus et la théophylline.

Effect of Myrtus Communis L. Extracts on Attenuation of Liver Normothermic Ischemia-Reperfusion Injury

The Common Myrtle (Myrtus communis L.) is rich in antioxidants, particularly in anthocyanin. It was recognized for its anti-inflammatory and anti-thrombotic effects. The aim of our work is to evaluate the effect of Common Myrtle on a model of hepatic ischemia-reperfusion in Rat. Two morphs were chosen: white fruit Myrtle and black fruit Myrtle. Within each morph, fruit and leaf were separated and obtained extract were used to determine their effects on the hepatic model of ischemia-reperfusion. Our work was conducted in three steps (1) Induction of hepatic ischemia (90 minutes) in Wistar Rat (2) injection of the Myrtle extract during 15 minutes before reperfusion (3) and reperfusion (2 hours). To evaluate the effect of Myrtle on ischemia-reperfusion, we have monitored transaminases levels, Monoethylglycinexylidide (MEGX) concentrations (to assess the liver metabolic capacity) and Malondialdehyde (MDA) concentration. The determination of total phenol extracts of Myrtle showed a significant difference between black fruit Myrtle (11.3 μg/ml), white fruit (27 μg/ml) and black fruit Myrtle leaves (94.3 μg/ml). The latter presented the highest antioxidant activity (86.54%). With the extract from the white fruit of Myrtle, we noted a decrease of AST and ALT, respectively, 1321 U/I and 773 U/I compared with I/R group was 5757 U/I and 5404 U/I and an increase in the MEGX concentrations and decrease in MDA. The testing of extracts of Myrtle in a model of hepatic ischemia showed a difference in the protective power against damage of ischemia-reperfusion, by origin and type of fruit (black or white).

Vancomycin Therapeutic Drug Monitoring in Cerebrospinal Fluid

Vancomycin penetrates poorly through the blood-brain barrier. Determination of vancomycin concentration in plasma is recommended. In contrast, its determination in cerebrospinal fluid (CSF) is rarely performed. We report the case of a 74-year-old man with post traumatic meningitis with vancomycin concentration measured in CSF.