In vitro drug sensitivity and clinical aspects of Plasmodium falciparum malaria in African children

OBJECTIVE: To compare body mass index (BMI), lipid, lipoprotein and apolipoprotein concentrations according to the Hind III and Pvu II restriction polymorphisms of the LPL gene in obese subjects. DESIGN: Cross sectional study of anthropometric and lipid variables in relation to genetic factors. SETTING: Nutrition Outpatient Clinic of Bichat Hospital in Paris, France. SUBJECTS: 236 unrelated patients (162 women and 74 men) were selected on the basis of 120% of ideal body weight. MAIN OUTCOME MEASURES: Anthropometry (body mass index, waist to hip ratio), blood lipids and lipoproteins, determination of LPL Hind III and Pvu II genotypes. RESULTS: Digestion with Hind III generated two alleles, H1 (absence of cutting site) and H2 (presence of cutting site), with frequencies of 0.30 and 0.70 respectively. Digestion with Pvu II generated two alleles P1 and P2 with frequencies of 0.49 and 0.51 respectively. The Hind III polymorphism was significantly associated with body mass index (BMI) (P < 0.05). The H2H2 genotype was associated with hypertriglyceridemia: 68% of the hypertriglyceridemic subjects have the H2H2 genotype vs 43% of the normotriglyceridemic group (P < 0.05). Plasma triglyceride levels varied significantly among the Hind III genotypes, H2H2 genotype having the highest total and VLDL-triglyceride levels; the Hind III polymorphism also showed a significant association with HDL2-cholesterol. These associations were only seen in women and were not explained by the variations in BMI and age. No significant associations were found between lipid traits and Pvu II genotype. CONCLUSION: These results suggest that genetic variation in the LPL gene in obese subjects is associated with hypertriglyceridemia and possibly with a predisposition to obesity.     

Quantification of blood echogenicity: evaluation of a semiquantitative method of grading spontaneous echo contrast

Spontaneous echo contrast (SEC) is an echogenic, swirling pattern of blood flow which may be observed by transesophageal echocardiography (TEE) in the left atrium in low flow states, such as atrial fibrillation (AF). The presence of SEC has been proposed as a marker of increased thromboembolic risk. Evaluation of the severity of SEC might be useful in stratification of thromboembolic risk. The aim of this study was to validate a semiquantitative method of grading SEC against quantitative videodensitometric analysis. TEE studies were performed in 50 patients with AF. The severity of left atrial SEC was graded by three independent observers and by videodensitometry. There was a strong, positive correlation between the semiquantitative grades of SEC and quantitative videodensitometric scores (r = 0.85, P < 0.0001). Inter- and intraobserver correlations in the grading of SEC were very high (observer 1 vs. 2: r = 0.98, P = 0.0001; observer 1 vs. 3: r = 0.93, P = 0.0001; observer 1 vs. 1: r = 0.97, P = 0.0001). Semiquantitative grading of SEC can be performed rapidly and reliably by experienced observers. These results support the use of semiquantitative grading in studies of the pathogenesis and prognostic implications of SEC.     

Low- and high-density lipoproteins as mitogenic factors for vascular smooth muscle cells: individual, additive and synergistic effects

The mitogenic activities of low (LDL)- and high (HDL)-density lipoproteins have been examined in cultures of human vascular smooth muscle cells (VSMC). LDL and HDL3 dose-dependently (EC50 values approximately 50 micrograms/ml) stimulated DNA and protein synthesis ([3H]-thymidine and [3H]-leucine incorporation, respectively) in the absence of exogenously added mitogens. The synthetic responses of VSMC to combinations of LDL and HDL3 were additive, indicating that each lipoprotein mediates discrete effects. LDL or HDL3 promoted VSMC proliferation under strict mitogen-free conditions, but this growth response was not sustained. VSMC exposed to combinations of lipoproteins (either LDL or HDL3) and growth factors (either PDGF-BB, EGF, bFGF or IGF) exhibited synergistic DNA synthesis responses. In the combined presence of PDGF-BB and either LDL or HDL3, VSMC proliferation was sustained. Anionized lipoprotein preparations (oxidized, acetylated, carbamylated or malonimylated) also stimulated DNA and protein synthesis. Since the antioxidant beta-hydroxylated toluene did not block the effect of native LDL on DNA synthesis, and fucoidin, a specific competitor for the 'scavenger' receptor, did not inhibit oxidized LDL-induced DNA synthesis, activation of mitogenic signals by lipoproteins does not depend on lipid peroxidation. Rather, the apparent intrinsic mitogenic potential of lipoproteins may depend upon their direct activation of replication-coupled signal transduction systems.     

Santolindiacetylene, a polyacetylene derivative isolated from the essential oil of Santolina canescens

The yield, composition, and some pharmacological activities (hepatoprotective and antioxidant) of the essential oil of Santolina canescens aerial parts have been investigated. The essential oil qualitative data were determined by gc and gc-ms. The main component, santolindiacetylene [1], was isolated and characterized by spectral methods, and the structure assigned as 1-(2'-naphthyl)hexa-2,4-diyne. The protective activities of the essential oil and its main component [1] were evaluated against carbon tetrachloride-induced hepatotoxicity in a rat model. In both cases a significant hepatoprotective effect was observed, as evident from the strong decrease of elevated GPT serum levels caused by carbon tetrachloride-induced hepatic damage.