(n-3) fatty acid supplementation in moderately hypertriglyceridemic adults changes postprandial lipid and apolipoprotein B responses to a standardized test meal.

The effects of (n-3) fatty acids on the postprandial state were investigated by monitoring the alimentary responses to identical test meals fed to adults [n = 11; fasting triacylglycerol (TG) 2.55 +/- 0.24 mmol/L; mean +/- SEM] after a self-selected diet baseline period (BLP) and then after a 6-wk (n-3) fatty acid period (FOP) [ approximately 5.2 g (n-3) fatty acids] and a 6-wk control oil period (COP) administered in random order. Samples were drawn immediately prior to the test meal (time 0) and then hourly from 2 to 6 h postmeal. Postprandial plasma triacylglycerol (TG) and TG-rich lipoprotein (TRL) TG apo B48, and B100 absolute concentrations were significantly lower after FOP than after COP or BLP, while plasma cholesterol was unchanged. Normalizing the results as increments over time 0 eliminated the diet effect on all but plasma TG. Time remained a significant effect for plasma TG, TRL TG, and TRL TC. Finally, only absolute TRL B48 and absolute and incremental plasma TG concentrations displayed significant time-diet interactions. These results suggest that postprandial TRL apo B reductions are likely caused by (n-3) fatty acid suppression of both hepatic and intestinal apoB secretion/synthesis. Altered TRL metabolism, i.e. changes in postprandial TG, cholesterol, apo B48, and increase in LDL particle size, may represent an additional mechanism for the reduced heart disease risk associated with fish [(n-3) fatty acid] consumption.     

A historical and molecular phylogeny of BCG strains

Bacillus Calmette-Guérin (BCG) is the name given to a family of vaccines derived in 1921 by the in-vitro attenuation of Mycobacterium bovis. Subsequently, BCG seed lots were distributed globally, and both phenotypic and genotypic differences between strains have been described. As a step to understanding BCG diversity, we have reviewed the English and French historical record on 13 strains and DNA was extracted from these strains for restriction-fragment-length-polymorphism study. The written record suggests "early strains" obtained from the Pasteur Institute between 1924 and 1926 and "later strains" obtained after 1931. Molecular typing resulted in 3 clades, based on variability in IS6110-typing and the presence of mpt64 gene. With two exceptions, these clades correspond with strains obtained in 1924-26 (IS6110-2/mpt64+), 1926-31 (IS6110-1/mpt64+), and 1931 or later (IS6110-1/mpt64-) This analysis demonstrates that BCG has undergone genetic changes since 1921, consistent with ongoing in-vitro evolution.     

Adsorption/desorption of human serum albumin on hydroxyapatite: a critical analysis of the Langmuir model.

We studied the adsorption of human albumin onto synthetic hydroxyapatite, using a radiotracer technique and a special flow cell. Adsorption was studied under various conditions corresponding to different thermodynamic paths. It appears that (i) as is the usual case, the isotherms obtained within a short time range (a few hours) do not correspond to a true equilibrium situation; (ii) when the adsorption process is followed for longer times, which is necessary at low bulk concentrations, one always reaches the plateau surface adsorption; (iii) this plateau value is independent of the "history" of the adsorption process and corresponds well to the jamming limit predicted by the random sequential adsorption model; and (iv) surface denaturation, leading to enhanced surface binding and thus decreasing desorption constants, is the important phenomenon that can partly and qualitatively explain our observations. Its time dependence, however, remains to be clarified.     

Evidence for oxidative stress in bronchiolitis obliterans syndrome after lung and heart-lung transplantation. The Munich Lung Transplant Group

Bronchiolitis obliterans syndrome (BOS) is the most serious long-term sequel of lung or heart-lung transplantation (H/LTX). Neutrophilia in the lower respiratory tract is a prominent feature of BOS. Because polymorphonuclear leukocytes (PMN) are capable of releasing large quantities of reactive oxygen species, we measured indicators of oxidative stress and glutathione levels representing antioxidant defense in H/LTX patients (HLTX, n=6; double-LTX, n=7; single-LTX, n=9). We analyzed 19 bronchoalveolar lavage (BAL) samples from 13 non-BOS patients (nine female, four male: age 39+/-4 years) and 17 BAL samples from nine BOS patients (five female, four male: age 33+/-2 years). PMN were the predominant BAL cell population in BOS (61.7+/-7.8% vs. 12.3+/-3.4%, P<0.001). Myeloperoxidase activity in the epithelial lining fluid and oxidized methionine residues in BAL-derived proteins were elevated in BOS (8.6+/-1.6 U/ml vs. 2.2+/-0.6 U/ml, P<0.01; and 12.6+/-1.1% vs. 7.7+/-0.8%, P<0.001, respectively). In addition, the concentration of reduced glutathione in epithelial lining fluid was decreased in BOS (162.6+/-20.1 microM vs. 345.8+/-57.1 microM, P<0.01), whereas the proportion of oxidized glutathione was increased (13.9+/-2.0O% vs. 6.7+/-1.2%, P<0.001). PMN, myeloperoxidase, and oxidized methionine residues were inversely correlated, whereas reduced glutathione was positively correlated with forced expiratory volume in 1 sec (P<0.05 to P<0.001). We conclude that excessive oxidative stress and a lack of glutathione are associated with BOS after H/LTX and may play relevant roles in the development of this disorder.     

Genetic distances for the study of infectious disease epidemiology

Molecular epidemiologic studies of infectious pathogens 1) generate genetic patterns from a collection of microorganisms, 2) compare the degree of similarity among these patterns, and 3) infer from these similarities infectious disease transmission patterns. The authors propose a quantitative approach using genetic distances to study the degree of similarity between patterns. Benefits of such genetic distance calculations are illustrated by an analysis of standard DNA fingerprints of Mycobacterium tuberculosis in San Francisco collected during the period 1991-1997. Graphical representation of genetic distances can assist in determining if the disappearance of a specific pattern in a community is due to interruption of transmission or ongoing evolution of the microorganism's fingerprint. Genetic distances can also compensate for varying information content derived by DNA fingerprints of contrasting pattern complexity. To study demographic and clinical correlates of transmission, the authors calculated the smallest genetic distance from each patient sample to all other samples. With correlation of genetic distances and nearest genetic distances with previously understood notions of the epidemiology of M. tuberculosis in San Francisco, factors influencing transmission are investigated.     

Therapeutic advantages of Auger electron- over beta-emitting radiometals or radioiodine when conjugated to internalizing antibodies

Recent studies suggest a higher anti-tumour efficacy of internalizing monoclonal antibodies (MAbs) when labelled with Auger electron emitters, as compared with beta-emitters. The aim of this study was to compare the anti-tumour efficacy and toxicity of the internalizing MAb, CO17-1A, labelled with Auger electron emitters (125I, (111)In) versus conventional beta(-)-emitters (131I, 90Y) in a colon cancer model, and to assess whether the residualizing radiometals may have therapeutic advantages over the conventionally iodinated conjugates. Biodistribution studies of 125I-, (111)In- or 88Y-labelled CO17-1A were performed in nude mice bearing subcutaneous human colon cancer xenografts. For therapy, the mice were injected with either unlabelled or 125I-, 131I-, (111)In- or 90Y-labelled CO17-1A IgG2a, whereas control groups were left untreated or were given a radiolabelled isotype-matched irrelevant antibody. The influence of internalization was assessed by comparing the results with those obtained with an anti-carcinoembryonic antigen (CEA) antibody which does not internalize to a relevant extent. The maximum tolerated activities (MTA) and doses (MTD) of each agent were determined. Myelotoxicity and potential second-organ toxicities, as well as tumour growth, were monitored. Bone marrow transplantation (BMT) was performed in order to enable dose intensification. Radiometals showed significantly better tumour-to-blood ratios than the respective iodinated conjugates. The MTAs of 131I- and 125I-CO17-1A without artificial support were 11.1 MBq (300 microCi) and 111 MBq (3 mCi), respectively; the MTA of the metals was reached at 4 MBq (100 microCi) for 90Y-, and at 85 MBq (2.3 mCi) for (111)In-CO17-1A. Myelotoxicity was dose limiting in all cases. BMT enabled an increase in the MTA to 15 MBq (400 microCi) of 131I-labelled CO17-1A, to 4.4 MBq (120 microCi) of 90Y-labelled CO17-1A, and to 118 MBq (3.2 mCi) of (111)In-labelled CO17-1A, while the MTA of 125I-CO17-1A had not been reached at 185 MBq (5 mCi) with BMT. Whereas no significant therapeutic effects were seen with unlabelled CO17-1A, tumour growth was retarded significantly with its radiolabelled forms. The therapeutic results were significantly (P<0.01) better with both Auger electron emitters (125I and (111)In) than with the beta-emitters, and, in accordance with the biodistribution data, a trend towards better therapeutic results was found with radiometals (more complete remissions) as compared with radioiodine. In contrast, at equitoxic doses, no significant difference was observed in the therapeutic efficacy of 131I- versus 125I-labelled non-internalizing anti-CEA antibody, F023C5. These data suggest that, at equitoxic doses, the therapeutic efficacy of internalizing MAbs labelled with Auger electron emitters, such as 125I or (111)In, is superior to that of internalizing MAbs labelled with conventional beta-emitters. The lower toxicity of Auger electron emitters may be due to the short path length of their low-energy electrons, which can reach the nuclear DNA only if the antibody is internalized (as is the case in antigen-expressing tumour tissue, but not in the stem cells of the red marrow).     

Pregnant woman and road safety: a numerical approach. Application to a restrained third trimester pregnant woman in frontal impact

Objectives

The goal of our work is the development of a numerical model of pregnant woman in driving position. We present an application to the study of injury mechanisms during a frontal car crash for a seat belt restrained pregnant woman in driving position.

Materials and methods

We integrated a digital representation of a pregnant uterus, foetus and placenta in a previous existing numerical model of non pregnant Human body in driving position, the Humos model^®. The realization of a numerical simulation of a frontal car crash enabled us to analyze the part played by the safety belt in the organic traumatisms.

Results

Three phases were highlighted. The first phase consists of a translation forwards of the pregnant uterus during the impact. The second phase is a rotation forwards in the sagittal plan of the pregnant uterus with for axis of rotation the posterior wall of the pubis. The third phase is a vertical adjustment coupled to a translation of the uterus towards the back. This translation leads the uterus to impact the spine.

Conclusion

The development of a pregnant numerical model in the field of accidentology allows the analysis of organic traumatisms. That makes it possible to study the role played by the existing safety systems. This model might make it possible to develop safety systems specific to the pregnant woman.