Toll-like receptor 2-deficient mice are protected from insulin resistance and beta cell dysfunction induced by a high-fat diet.

AIMS/HYPOTHESIS: Inflammation contributes to both insulin resistance and pancreatic beta cell failure in human type 2 diabetes. Toll-like receptors (TLRs) are highly conserved pattern recognition receptors that coordinate the innate inflammatory response to numerous substances, including NEFAs. Here we investigated a potential contribution of TLR2 to the metabolic dysregulation induced by high-fat diet (HFD) feeding in mice. METHODS: Male and female littermate Tlr2(+/+) and Tlr2(-/-) mice were analysed with respect to glucose tolerance, insulin sensitivity, insulin secretion and energy metabolism on chow and HFD. Adipose, liver, muscle and islet pathology and inflammation were examined using molecular approaches. Macrophages and dendritic immune cells, in addition to pancreatic islets were investigated in vitro with respect to NEFA-induced cytokine production. RESULTS: While not showing any differences in glucose homeostasis on chow diet, both male and female Tlr2(-/-) mice were protected from the adverse effects of HFD compared with Tlr2(+/+) littermate controls. Female Tlr2(-/-) mice showed pronounced improvements in glucose tolerance, insulin sensitivity, and insulin secretion following 20 weeks of HFD feeding. These effects were associated with an increased capacity of Tlr2(-/-) mice to preferentially burn fat, combined with reduced tissue inflammation. Bone-marrow-derived dendritic cells and pancreatic islets from Tlr2(-/-) mice did not increase IL-1beta expression in response to a NEFA mixture, whereas Tlr2(+/+) control tissues did. CONCLUSION/INTERPRETATION: These data suggest that TLR2 is a molecular link between increased dietary lipid intake and the regulation of glucose homeostasis, via regulation of energy substrate utilisation and tissue inflammation.

Laser evoked potentials using the Nd:YAG laser.

Pain-related cortical potentials were evoked by skin stimulation of the face and the limbs with 5-ns-duration laser pulses delivered by a Q-switched Nd:YAG laser. Such laser pulses, in the nanosecond range, were able to induce pinprick pain sensations and to evoke reproducible laser evoked potentials (LEPs) without visible skin lesions for an energy density of less than 18 mJ/mm(2). Low energy densities, around 10 mJ/mm(2), were sufficient to reach the pain threshold and to induce LEP. The mean conduction velocity of the stimulated afferent fibers was close to 20 m/s, consistent with the stimulation of Adelta fibers. The amplitude of LEP correlated with pain perception rather than with energy density. The differences, such as wavelength and stimulus duration, between the Q-switched Nd:YAG laser we used and the lasers that are currently used in LEP studies (i.e., CO(2), argon, or Tm:YAG lasers in the millisecond range) are discussed. Our study opens novel perspectives in the LEP field of research by using a new type of laser with a very short pulse duration.

Laser tomography of heterogeneous scattering media using spatial and temporal resolution.

Time-resolved tomography is performed in transillumination by using 527 nm picosecond pulses from a passively mode-locked doubled Nd/glass laser and a streak camera to select photons according to their flight time. This work reports on the increase in contrast of a time-resolved profile of a 2 mm radius opaque object embedded in a scattering medium, constituted of diluted milk in a 30 mm thick cell. For spatial analysis, the emerging photons are detected through a 6 mm slit at the outlet face of the cell. Transmission profiles obtained as a function of time show that the contrast is enhanced for the shortest flight times, while the 'shadow' of the object is no longer detected after about 100 ps. Moreover, improvements in contrast are studied for different configurations of the model, to analyse separately the role of collimated and scattered photons. It is expected that such a tomographic method based on time-resolved absorption could be applied to imaging for more complex biological structures in the red and near-infra-red range.

In vivo transillumination of the hand using near infrared laser pulses and differential spectroscopy.

In vivo dual wavelength differential spectrography was performed on the hand of an adult male, using a collimated transillumination device. A pulsed laser with sufficiently high peak power and sufficiently low energy was employed so that transillumination could be realized without thermal damage. Spectrochemical analysis based on the absorbance of oxygen transporting molecules (OTM), i.e. haemoglobin in blood vessels and myoglobin in muscles, was performed along a 70 mm scanning line within the near-red infrared range. The two wavelengths used (675 and 800 nm) were chosen on the basis of the absorption spectrum of haemoglobin. The profiles computed with differential spectrography data related to the oxygen saturation of OTM are closely correlated with X-ray densitometry of the most vascularized tissues in the hand along the scanning line. In addition, at 675 nm, the profiles are rapidly modified as a function of the oxygen supply to the hand. Considering the accuracy obtained for the spatial localization of the OTM redox state, it is expected that these results could be applied to imaging.

[Old age and joint disease]. / Viellesse et maladies articulaires.

The seriousness of articular diseases in old persons is related to the loss of function and the rapid way this can lead to them being bed ridden. Rheumatoid polyarthritis is often difficult to distinguish from rhizomelic pseudopolyarthritis, these two diseases resemble each other at this age with the asthenia and loss of general health, the inflammatory pains which are peripheral and of nerve root origin. Among the metabolic arthropathies, articular chondrocalcinosis is frequent, and often latent, but sometimes it is destructive in particular in the hips and knees; septic arthritis today mainly occurs in the elderly, and the algoneurodystrophies are more frequent in old persons than in young subjects, following trauma or a hemiplegia. Arthrosis is obviously the main articular disease of senescence especially involving the joints of the lower limb, hip disease being less incapacitating than knee disease where surgical treatment is less often considered. The arthroses of the upper limbs especially of the shoulder are well tolerated. Osteochondromatosis, osteonecrosis of the internal condyle of the knee, the rapidly destructive arthropathies and hemarthrosis can develop as a complication of a simple arthrosis. In the spine vertebral hyperostosis is especially a disease of the elderly, it can occur alone or with an arthrosis of the posterior vertebral joints, a narrow spinal canal straight or narrowed. Medical treatment, physiotherapy, and finally surgery can give very satisfactory results in an old patient, avoiding loss of function, a miserable existence and becoming bed ridden.

Scanning spectrophotometry for the dynamic study of tissue respiration in intact organs.

For use with intact perfused organs a spectrophotometer system has been developed, both for dual-wavelength absorption measurements and for spectral scanning. A monochromator is used for illumination and scanning in the visible and near infrared. Optic fibres conduct light to the specimen under examination and from the specimen to a detecting photomultiplier. System control is exercised by a microcomputer, which also processes the collected data. The performance of the system on isolated perfused rat heart is demonstrated, in the spectral scanning mode and in the dual-wavelength mode, by studying simultaneously the kinetics of cytochrome aa3, and myoglobin oxidation-reduction.

Imaging mammalian tissues and organs using laser collimated transillumination.

Images of mammalian organs were built up using a Laser collimated transillumination device equipped with a bidirectional scanning setup. A microcomputer was used to run the scanning process, acquisition of detected signals and images restitution. The images featured a satisfactory resolution of optical discontinuities on both sample surfaces. Light scattering within biological tissues restricted the spatial discrimination encountered with geometrical selection approach. By combining space and time resolution at various wavelengths, the production of an efficient tomospectroscopy could be envisaged.