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Abstract: Active Denial Systems (ADS) is a millimetric wave radiation emitting technology now included in the non lethal weapon arsenal. Such devices emit electromagnetic, thus agitating water in the skin and causing feeling of heat enough that target individual retreats from the beam. They can be used at up to 1 km from the target. We have reviewed the literature on the interactions of millimetric waves (MMW) with biological systems. An opposition appears between the observations performed in the Former Soviet Union and Russia showing potential interaction sometimes deleterious while generally of good influence and used in therapy. By way of contrast, most of the other studies, performed in USA, address local acute effects, exclusively located on the skin and eyes of the target, and considered as completely reversible. [Copyright &y& Elsevier]

This retrospective cohort study deals with the causes of death among 57,000 military personnel who served in the French Navy surface vessels and were observed over the period 1975-2000. We successively compared the mortality rate and the specific causes of death between two groups differing in their potential exposure levels to radar. Occupational exposure was defined according to the on-board workplace (radar and control groups). The age-adjusted death ratios of the navy personnel were compared. For all causes of death, the results showed that 885 deaths in the radar group and 299 in the control group occurred (RR = 1.00 (95% CI: 0.88-1.14)). RRs were 0.92 (95% CI: 0.69-1.24) for neoplasms. For the duration of follow-up, the results did not show an increased health risk for military personnel exposed to higher levels of radio frequencies in the radar group, but the number of deaths was very small for some cancer sites.

LASIK eye surgery has become a very common practice for myopic people, especially those in the military. Sometimes undertaken by people who need to keep a specific medical aptitude, this surgery could be performed in secret from the hierarchy and from the institute medical staff. However, even though the eyes have been previously described as one of the most sensitive organs to electromagnetic fields in the human body, no data exist on the potential deleterious effects of electromagnetic fields on the healing eye. The consequences of chronic long-lasting radar exposures at power density, in accordance with the occupational safety standards (9.71 GHz, 50 W/m(2)), were investigated on cornea healing. The metabolic and clinical statuses after experimental LASIK keratotomy were assessed on the different eye segments in a New Zealand rabbit model. The analysis methods were performed after 5 months of exposure (1 hour/day, 3 times/week). Neither clinical or histological examinations, nor experimental data, such as light scattering, (1)H-NMR HRMAS metabolomics, (13)C-NMR spectra of lipidic extracts, and antioxidant status, evidenced significant modifications. It was concluded that withdrawing the medical aptitude of people working in electromagnetic field environments (i.e., radar operators in the navy) after eye surgery was not justified.

The increasing applications of microwaves, mainly in mobile phones and radar, induce a higher rate of exposed people, sometimes cause of worry. Eyeballs are hotspots of radiofrequency field radiation because of their anatomy and composition. We propose a review of the various effects on the eye. The studies are hardly comparable because the exposure systems, power densities and dosimetries are different. While the thermal effects on the eye are well known including cataracts, corneal edema, endothelial cell loss and retinal degeneration, the non-thermal effects are still controversial. Cell cycle abnormalities, early apoptosis were reported in experimental conditions likely due to oxidative stress, but the studies could not show any significant effect on human eyes when exposed to long-term and low-dose radiation. Next studies need to be closer to human exposure.

Terahertz technologies have recently been applied to develop high resolution imaging. Since practical portable systems can be designed, the possibilty has emerged to easily screen for biohazards and concealed objects, a procedure which usually requires remote analysis. Applications of THz are also envisaged in the medical field, because this technology offers a degree of accuracy never reached before in molecule analysis. Skin abnormalities and dental health care are two promising targets of THz applications. Nevertheless, potential hazards and health effects of THz exposure should be monitored carefully, particularly since some data suggest induction of genomic instability.

Potential human health hazards have been reported after exposure to electromagnetic fields at low power density. Increased oxidative stress has been suggested as a potential mechanism involved in long-term effect of such exposure. In the present work, yeast cultures were exposed for 20 min to a 9.71 GHz pulsed electromagnetic field at specific absorption rates (SAR) from 0.5 W/kg to 16 W/kg. Oxidative perturbations were investigated using ESR spin trapping experiments and their impacts on membrane fluidity were assessed using spin label five nitroxide stearate. The experiments using the water-soluble spin trap alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone and the lipid-soluble N-tert-butyl-alpha-phenylnitrone showed an increase of spin adduct production both in low power density exposure (SAR<4 W/kg) and in thermal conditions (SAR>4 W/kg). The membrane fluidity diminutions after exposure in all the conditions were consistent with lipid peroxidation. The overall results suggest an increase of the free radical production in the intra cellular compartment; however no effect on the yeast vitality was found.

Natural beta-cyclodextrin bears an internal crown consisting of six primary alcohol groups. Their removal leads to per(6-deoxy)beta-cyclodextrin (B6). The physicochemical properties of B6 and its interactions with membranes were investigated to give an evaluation of haemolytic activity and complexing properties of this chemical species. This was achieved by using surface tension and haemolytic activity (i.e.DH50 determination, the concentration inducing 50% haemolysis) measurements,1H-31P-NMR and EPR spectroscopies. Whereas B6 solubility in the water is close to that of natural beta CD (about 5 g/L at 20 degrees C) and exhibits amphiphilic properties greater than those of beta CD (log P: -1.36 at 300 K), B6 forms micelles in aqueous solution of 20 molecules, even at low concentration 0.8mM. In addition, B6 exhibits tensioactive properties leading to solubilization and even, in some cases orientation of synthetic membranes. Although no complex formation with membrane components was observed, NMR and ESR showed interactions with the surface of the membrane. Subsequently, B6 exhibits an important haemolytic activity, whose mechanism, different from that of beta CD, is discussed.

Active Denial Systems (ADS) is a millimetric wave radiation emitting technology now included in the non lethal weapon arsenal. Such devices emit electromagnetic, thus agitating water in the skin and causing feeling of heat enough that target individual retreats from the beam. They can be used at up to 1 km from the target. We have reviewed the literature on the interactions of millimetric waves (MMW) with biological systems. An opposition appears between the observations performed in the Former Soviet Union and Russia showing potential interaction sometimes deleterious while generally of good influence and used in therapy. By way of contrast, most of the other studies, performed in USA, address local acute effects, exclusively located on the skin and eyes of the target, and considered as completely reversible.

Four 2,3-diarylimidazo[1,2-a]pyridines (I, 1a-c) were synthesized as inhibitors of UV-induced apoptosis and showed quite different properties. First, only the pyridinyl derivative I showed protection in molt cells. From the supposed intracellular target, phospholipid membrane models were studied by (1)H, (2)H and (31)P NMR spectroscopy. All these molecules can incorporate the membrane bilayer of small unilamellar vesicles of lecithin (SUV). However, I is clearly closed to the external polar head of the lipids, and is relatively mobile in the layer. Conversely, the other molecules are strongly immobilized in the deep part of the external layer. (31)P solid-state NMR spectra recorded on phospholipid dispersions (multilayers vesicles (MLV)) completely excluded any detergent effect or any modification of temperature transition. The only structural or dynamic effect observed was a homogeneous, but limited, reduction in the chemical shift anisotropy in the presence of I, in agreement with its superficial location. (2)H NMR experiment performed on the same model using perdeuterated phospholipids showed no significant fluidity reduction at the level of terminal CD(3) groups in the presence of 1a-c, according to their deep location. Finally, their interactions with synthetic oligonucleotide, d(CGATCG)(2) was studied showing non specific interactions of 1a on the external GC pair, while no interaction was observed with the other derivatives.

Aerosols produced during impacts of depleted uranium (DU) penetrators against the glacis (sloping armour) and the turret of a tank were sampled. The concentration and size distribution were determined. Activity median aerodynamic diameters were 1 microm (geometric standard deviation, sigma(g) = 3.7) and 2 microm (sigma(g) = 2.5), respectively, for glacis and turret. The mean air concentration was 120 Bq m(-3), i.e. 8.5 mg m(-3) of DU. Filters analysed by scanning electron microscopy (SEM) and X ray diffraction showed two types of particles (fine particles and large molten particles) composed mainly of a mixture of uranium and aluminium. The uranium oxides were mostly U3O8, UO2.25 and probably UO3.01 and a mixed compound of U and Al. The kinetics of dissolution in three media (HCO3-, HCl and Gamble's solution) were determined using in-vitro tests. The slow dissolution rates were respectively slow, and intermediate between slow and moderate, and the rapid dissolution fractions were mostly intermediate between moderate and fast. According to the in-vitro results for Gamble's solution, and based on a hypothetical single acute inhalation of 90 Bq, effective doses integrated up to 1 y after incorporation were 0.54 and 0.56 mSv, respectively, for aerosols from glacis and turret. In comparison, the ICRP limits are 20 mSv y(-1) for workers and 1 mSv y(-1) for members of the public. A kidney concentration of approximately 0.1 microg U g(-1) was predicted and should not, in this case, lead to kidney damage.

Per (3.6-anhydro-2-O-carboxymethyle)- alpha-cyclodextrin ([1]) is a polydentate analog of EDTA, a well-known cation chelating reagent. [1] exhibits strong affinities in vitro for lanthanids, cobalt and also for uranyl cations. Hence, a 1:1 stoechiometry and a high affinity for uranyle (6

The solution structure of the complex formed between d(CGATCG)(2) and 2-(pyrido[1,2-e]purin-4-yl)amino-ethanol, a new antitumor drug under design, has been resolved using NMR spectroscopy and restrained molecular dynamic simulations. The drug molecule intercalates between each of the CpG dinucleotide steps with its side chain lying in the minor groove. Analysis of NMR data establishes a weak stacking interaction between the intercalated ligand and the DNA bases; however, the drug/DNA affinity is enhanced by a hydrogen bond between the hydroxyl group of the end of the intercalant side chain and the amide group of guanine G6. Unrestrained molecular dynamic simulations performed in a water box confirm the stability of the intercalation model. The structure of the intercalated complex enables insight into the structure-activity relationship, allowing rationalization of the design of new antineoplasic agents.

Two pyrido[1,2-e]purins with different side chain lengths have been synthesized to test their ability to intercalate inside DNA. The interactions of these drugs with synthetic oligodeoxy nucleotide d(CGATCG)2 have been studied with 1H and 31P NMR spectroscopy experiments. Molecule 1, rather amphiphilic (Log(P) = 1.3, due to its hydroxypropyl side chain) can intercalate GC sites of the mini helix, under a fast exchange mechanism and a 2:1 stoechiometry. The presence of a six methylen side chain in 2 (hydroxyhexyl side chain) is responsible for a relatively poor solubility of this molecule in water (log P = 2.3). Binding, rather than intercalation, of 2 to the external GC pairs is observed, severely limited by the formation of aggregates. Models for the intercalation of 1, are proposed using energy minimizations and Molecular Dynamics (MD) calculations subject to restraints from experimental nOe connectivities. Simulations and experiments both indicate fast exchange of 1 in its intercalation site.

13Carbon monoxide (CO), when bound to hemoglobin, yields (13)C NMR resonances (CO-Fe resonances). 100% CO liganded tetrameric hemoglobin ((13)C-labelled CO) was prepared for (13)C-NMR observation. The information about exchange kinetics between the four subunits (2alpha and 2B), were derived by changing the temperature (in the range 275-313K) and the observation frequency (4.7T, 9.4T and 18.8T). The first results confirmed previous observations of slow exchange between free and bound (2alpha and 2B together) CO. Besides, the exchange between alpha and B subunits were found slow at the NMR timescale, even under 313K and 4.7T conditions. Furthermore, intermediate temperatures (283-303K) allowed the observation of broad unresolved lines at 9.4T, corresponding both to CSA contribution and exchange linebroadening. Finally, low temperatures (less than 277K, at 9.4T) provided four relatively broad - but clearly distinguishable lines - indicating that a slow exchange rate was reached between four Fe-CO geometries on the subunits. This also indicated that two main Fe-CO orientations were different, even between similar chains (alpha1-alpha2 and B1-B2).

The complexation of mustard gas Cl(CH(2))(2)S(CH(2))(2) Cl, HD, yperite) and of ethers and thioethers derivatives by cyclodextrins: natural alpha-cyclodextrin (ACD) and substituted B-cyclodextrins was studied by NMR. A 1/1 stoechiometry was found in all cases, while affinity constants were found relatively weak (from 5 M(-1) to 100 M(-1)). However, these results show that chelation of HD by cyclodextrins can be reasonably expected, especially if chemical modifications provide stronger affinity constants.

Interactions of three pryridopurines differing by their side chain, -SCH2-Phe [1], -SCH2-CHOH-CH3 [2], and -SCH2-CHOH-CH2OH [3], with model membranes were studied by proton, phosphorus and carbon NMR. Their incorporation in phospholipid multilayers induced a membrane rigidification without altering ther main bilayer structure nor the phase transition. Depending on the more or less amphiphilic properties, these molecule have different behavior when included in small unilamellar vesicles: hydrophobic [1] is found in the deepest part of the membrane, while [2] lies at an intermediate location in the layer. [3] is more hydrophilic: its aromatic moiety is in the intermediate part of the membrane whereas the side chain is found oriented towards the superficial part of the layer. Furthermore, the amphiphilic molecule [2] has transmembrane transport abilities when in the presence of large unilamellar vesicles.