Effect of PACAP treatment on kidney morphology and cytokine expression in rat diabetic nephropathy.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide, exerting diverse effects. One of its frequently examined functions is cell protection, which is achieved mainly via inhibiting apoptotic, inflammatory and oxidative processes. All its three receptors (PAC1, VPAC1, VPAC2) are expressed in the kidney and PACAP has been shown to have protective effects against different renal pathologies. Diabetic nephropathy is the leading cause of end stage renal disease. The aim of the present study was to investigate the possible ameliorative effect of PACAP in streptozotocin-induced diabetic nephropathy and to evaluate its anti-inflammatory effect in this model. Diabetes was induced by a single intravenous injection of streptozotocin (65 mg/kg) in male Wistar rats. PACAP-treated animals were administered ip. 20 µg PACAP every second day, while untreated animals were given vehicle. Kidneys were removed after 8-weeks survival. Besides the complex histological analysis (glomerular PAS positive area/glomerulus area, tubular damage, arteriolar hyalinosis), expression of several cytokines was evaluated by cytokine array and Luminex assay. Histological analysis revealed severe diabetic changes in kidneys of control diabetic animals (glomerular PAS-positive area expansion, tubular damage, Armanni-Ebstein phenomenon). PACAP treatment significantly diminished the damage. Diabetic kidneys showed significant cytokine activation compared to their healthy controls. PACAP was effective in downregulation of several cytokines including CINC-1, TIMP-1, LIX, MIG, s-ICAM. To conclude, PACAP is effective in ameliorating diabetic nephropathy at least partly through its well-known anti-inflammatory effect. These results raise the opportunity for the use of PACAP as a possible therapeutic or preventive method in treating the complications of diabetes.

Computer simulation of the spin-echo spatial distribution in the case of restricted self-diffusion.

This article concerns the question of a proper stochastic treatment of the spin-echo self-diffusion attenuation of confined particles that arises when short gradient pulse approximation fails. Diffusion is numerically simulated as a succession of random steps when motion is restricted between two perfectly reflecting parallel planes. With the magnetic field gradient perpendicular to the plane boundaries, the spatial distribution of the spin-echo signal is calculated from the simulated trajectories. The diffusion propagator approach (Callaghan, "Principles of Nuclear Magnetic Resonance Microscopy," Oxford Univ. Press, Oxford, 1991), which is just the same as the evaluation of the spin-echo attenuation by the method of cumulant expansion in the Gaussian approximation, with Einstein's approximation of the velocity correlation function (VCF) (delta function), agrees with the results of simulation only for the particle displacements that are much smaller than the size of the confinement. A strong deviation from the results of the simulation appears when the bouncing rate from the boundaries increases at intermediate and long gradient sequences. A better fit, at least for intermediate particle displacements, was obtained by replacing the VCF with the Oppenheim--Mazur solution of the Langevin equation (Oppenheim and Mazur, Physica 30, 1833--1845, 1964), which is modified in a way to allow for spatial dependence of particle displacements. Clearly, interplay of the correlation dynamics and the boundary conditions is taking place for large diffusion displacements. However, the deviation at long times demonstrates a deficiency of the Gaussian approximation for the spin echo of diffusion inside entirely closed pores. Here, the cumulants higher than the second one might not be negligible. The results are compared with the experiments on the edge enhancement by magnetic resonance imaging of a pore.

MRI edge enhancement as a diffusive discord of spin phase structure.

The enhancement of magnetic resonance image intensity near impermeable boundaries can be nicely described by a new approach where the diffusional spin echo attenuation is linked to the correlation function of molecular motion. In this method the spin phase structure created by the applied gradient is considered to be a composition of plane waves with the wave vectors representing feasible momentum states of a particle in confinement. The enhancement of edges on the magnetic resonance images (MRI) comes out as a discord of plane waves due to particle motion. It results from the average of the wave phase by using the cumulant expansion in the Gaussian approximation. The acquired analytical expression describes the MRI signal space distribution where the enhancement of edges depends on the intensity and the duration of gradient sequence as well as on the length of the mean squared particle displacement in restricted geometry. This new method works well with gradients of general waveform and is, therefore, suitable for imaging sequences where finite or even modulated gradients are usually used.