Protective effect of Ulva lactuca extract during hepatic cold preservation in rats

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

[Development and validation of a new HPLC method for determination of lamotrigine and clinical application]

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

[Pharmacokinetik population of methotrexate in Tunisian population with acute lymphoblastic leukemia]

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

[Hypovitaminosis D in Tunisian osteoporotic post menopausal women and its relationship with bone fracture]

The purpose of this study is to evaluate the frequency of hypovitaminosis D in Tunisian osteoporotic women and to search an eventual association between vitamin D status and the fracture risk. A transverse descriptive study enrolled 134 osteoporotic menopausal women aged 50 years or more. We measured calcium, phosphorus, albumin, alkaline phosphatase, creatinine and 25 hydroxyvitamin D [25 [OH] vit D]. Bone mineral density [BMD] was measured for all and osteoporotic women were defined for a T-score of -2,5 or less in the spine, hip or femoral neck .Two groups were defined: G1 with fracture and G2 without fracture .We used SPSS 10.5, X2 tests and a statistical significance level of p< 0,05. Women in G1 [n= 102] were more aged than those in G2 [n= 32] and their menopause was more ancient. Hypovitaminosis D was found in 45,2% of all women, respectively in 50,98% of G1 and 25% of G2. The mean level of vitamin D was more important in G2 [27,5+ 15,1 vs 21,3 + 12,8 ng/ml; p=0,002]. BMD in femoral and lumbar were statistically lower when fractures are present [p< 0,001]. Our study shows that women with hypovitaminosis D [vit D < 20 ng/ml] are prone to osteoporotic fractures. All fracture in community in menopausal women, should be assessed with BMD and screening for 25 [OH] vit D. Increasing life expectancy in our country suggests that this public health problem will grow in the years to come, pointing out the importance of better management of osteoporosis and hypovitaminosis D to prevent fractures

[ interest of biochemical markers of bone turnover for monitoring treatment of postmenopausal osteoporosis]

Postmenopausal osteoporosis is especially female pathology, whose incidence increases with age. The purposes of this study are to evaluate the level of bone turnover by the determination of markers of bone formation [PAL, BAP] and marker of bone resorption [CTX] in the osteoporotic women, to study the correlations between bone biochemical markers, clinical parameters and radiological measurements and to assess the interest of biochemical markers in therapeutic monitoring after 6 months of antiresorptive treatment. The authors report a prospective study of 134 osteoporotic women classified in two groups according to the presence of osteoporotic fracture. Patients of the first group G[1] [n=102] with fractures, were treated by the bisphosphonates [risedronate], whereas the ones of the second group G[2] [n=32] without fractures, were submited to calcic supplementation and vitamin D. The analyses showed that the femoral and lumbar BMD were statistically lower in the presence of osteoporotic fractures. However, the values of CTX were statistically higher in the patients of G[1] group compared to those of the G[2] group [0,708 +/- 0,332 mg/ml versus 0,514 +/- 0,225 mg/ml]. The CTX were statistically correlated with the femoral and lumbar BMD [r = -0,21, p<0,05 and r = -0,348, p<0,001]. The hypovitminosis were observed in 50,98% [52/102] of women with osteoporotic fractures, whereas it was only 25% [8/32] in women without fractures. After 6 months of treatment by the bisphosphonates, the PAL, the BAP and the CTX have decreased with an average of, respectively, 19%, 46,5% and 62,9%. These variations were significantly more important in G[1] group. The biochemical markers of bone turnover, in particular those of the resorption [CTX], can predict the post-menopausal woman's bone loss evaluated by BMD, the risk of fractures and the efficiency of the bone treatments