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1.
Tunisie Medicale [La]. 2016; 94 (4): 276-283
in English | IMEMR | ID: emr-185052

ABSTRACT

Background: The researchers find means for the improvement of the organs conservation allowing prolonging the durations of the cold ischemia [before transplantation] with preservation of the maximum of their functional activity


Aim: To evaluate the extracts stemming from the green seaweed Ulva lactuca to improve the organs conservation solution against cold hepatic-ischemia effects in Wistar rats


Methods: Animals were randomized between 3 groups: sham group [shortly preserved]; livers were washed with saline solution [NaCl 9 %], and then placed in a preservation solution [Krebs-Henseleit] for 30 min at 4[degree]C. For the other two groups [non-treated group and treated group with Ulva lactuca extract], livers were preserved under the same conditions for 24 h. After liver conservation, we realized an extraction of mitochondria for the dosage of MDA and to evaluate the mitochondrial respiration. In the hypothermic ischemia model AST and ALT activities, and Na+, Ca2+, K+ and Cl- monitoring, were assessed in the preservation liquid. Fragments of livers were used for histological analysis


Results: AST and ALT levels decrease significantly in the treated group [185 +/- 35.2 and 163.6 +/- 24.5 U/I] compared to the non-treated group [644.3 +/- 254.4 and 925.7 +/- 459.7 U/I] respectively. The percentage of lipid peroxidation inhibition increased of 26.43 +/- 1.33% and the percentage of mitochondrial activity increased of 38.8 +/- 4.3%, between treated and non-treated groups. Extensive ballooning degeneration [reversible lesion] and apoptosis cell was found in the non-treated group


Conclusion: Ulva lactuca extract protects hepatocytes from the deleterious effect induced by hypothermic ischemia in rats

2.
Tunisie Medicale [La]. 2015; 93 (8/9): 565-568
in French | IMEMR | ID: emr-177404

ABSTRACT

Background: Lamotrigine is an effective anticonvulsant drug used in the treatment of epilepsy. It has a narrow therapeutic range, a large inter and intra-individual pharmacokinetic variability and some concentration-dependent side effects


Aim: The aim of this study was to develop and validate a new method for lamotrigine quantitation in plasma using HPLC with UV/visible detection


Methods: A rapid HPLC-UV method was developed for the determination of lamotrigine in plasma. All solvents used were HPLC grade


Results:After liquid-liquid extraction, chromatographic separation was achieved using an RP 18 [250 mm] column. The mobile phase was composed of acetonitrile and 0.1 M potassium dihyrogenophosphate [25/75] [v/v]. Barbital sodium was used as internal standard. This technique was linear over the 2 micro g/mL to 50 micro g/mL range [r= 0.99]. Detection and quantification limits were 0.07 micro g/mL and 0.21 micro g/mL, respectively. Within-day coefficient of variation [13.37 to 16%] and day-to-day coefficients of variation [15.68 to 16.63%] at three different concentrations. Under these conditions, each analysis required no longer than 10 min. We finally evaluated the plasma concentrations of lamotrigine in Tunisian patients treated with this drug


Conclusion: The results found are similar to those previously described and the developed method is repeatable and reproducible. It can be used for clinical applications

3.
Tunisie Medicale [La]. 2015; 93 (12): 760-765
in French | IMEMR | ID: emr-177456

ABSTRACT

Background: The use of high dose of MTX in the treatment of the leukemia is actually better controlled by renal preparation, control of plasma concentrations and administration of folinic acid. However, High dose MTX has been proven to cause substantial toxicity and have high intra-and inter-patient variability. Population pharmacokinetic analysis is a useful tool for identification of sources of pharmacokinetic variability during anticancer drug development and can aid the design of alternative dosing regimens to enhance their efficacy and safety


Aim: The aim of our study is to developed and validate a population pharmacokinetics model of our population. We hereby describe the clinical covariates [age, sex and clearance of the creatinine] that influence MTX pharmacokinetic for predicting optimal dose to reduce MTX toxicity


Method: It is a prospective study achieved between January 2005 to January 2012 in the Service of Clinical Pharmacology. Including 273 patients treated for acute lymphocytic leukaemia 2582 plasma concentration was achieved. The data have been analyzed with Nonmem[copyright sign] software [non linear regression to mixed effect]


Results:The age of our patients varied from 2 to 23 years with an average of 13 years. The patients received high dose MTX therapy [1 to 8 g/m2] in 24 hours infusion every 15 days. Three compartiment models describe the pharmacokinetic of MTX. The most important covariables affecting the model were clearance of the creatinine, age and weight. We obtained a good correlation between the predicted and the observed concentrations


Conclusion: The development of population pharmacokinetics model of MTX allows us to propose a therapeutic diagram adapted to every patient according to its morphological and pharmacological features while taking in consideration the therapeutic objective

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