[Non-equilibrium properties of drug permeation through stratum corneum in vitro].

AIM: To illustrate the non-equilibrium properties of drug permeation through stratum corneum (SC) to provide theory and method for transdermal drug delivery. METHODS: The system of side-by-side permeation chambers in vitro was isolated, thus conditions for equilibrium state were decided. And a network thermodynamic model was established. Non-equilibrium and leakage experiments were completed with which tinidazole was pattern drug. RESULTS: The properties of non-equilibrium including: long term to reach equilibrium state; delay-start of the permeation; uncertainty of initial drug permeable flux. The properties of leakage including: degression of drug permeable flux; changeability of permeation time constant. CONCLUSION: The permeation cell is believed to be a non-linear and time variable system.

Studies on cognitive and dynamic brain responses to mono-stimulation in human.

Researchers have used primate animals to investigate brain functions at neuron level or even every different level and have achieved a lot progresses and results. However, none of them involved people in their entirety and few studied the dynamics of unfolding brain function as the whole under the life condition of people. Hence people still don't understand well how their cognitive process is completed. We isolated the relatively independent visual system from the complex human body and studied its linkage to cognition. Therefore, by linking stereopsis and cognition this paper studies the cognitive and dynamic response to external mono-stimuli using the electrophysiological method. Investigators directly took part in the entire experimental processes as volunteers. They were able to experience the details of complete cognitive response produced by external stimuli and sense the formation of stable cognition with robustness through personal understanding. The results showed that cognition is a dynamic process of multiple factors. In particular, a new N2 waveform of cognitive characteristics is found to respond to a single stimulus at the advance visual cortex and this N2 waveform is also verified by computing its nonlinear complexity. Differences between dynamic responses to red-blue stereogram pair (RBSGP) and black-white one luminance had response waveforms differed considerably. And the time delay of the peak-to-peak N2 wave in the cognitive dynamic response to the onset of red-blue contrast was greater than the time delay of corresponding N2 peak-to-peak in the response to black-white contrast. Furthermore, our result concurs with the latest advance by A. Anzai in the research of neuron cellular physiology.

Expression of a fusion protein of human ciliary neurotrophic factor and soluble CNTF-receptor and identification of its activity.

Ciliary neurotrophic factor (CNTF) has pleiotropic actions on many neuronal populations as well as on glia. Signal transduction by CNTF requires that it bind first to CNTF-R, permitting the recruitment of gp130 and LIF-R, forming a tripartite receptor complex. Cells that only express gp130 and LIF-R, but not CNTF-R are refractory to stimulation by CNTF. On many target cells CNTF only acts in the presence of its specific agonistic soluble receptors. We engineered a soluble fusion protein by linking the COOH-terminus of sCNTF-R to the NH2-terminus of CNTF. Recombinant CNTF/sCNTF-R fusion protein (Hyper-CNTF) was successfully expressed in COS-7 cells. The apparent molecular mass of the Hyper-CNTF protein was estimated from western blots to be 75 kDa. Proliferation assays of transfected BAF/3 cells in response to CNTF and Hyper-CNTF were used to verify the activity of the cytokines. The proliferative results confirmed that CNTF required homodimerization of the gp130, CNTF-R and LIF-R receptor subunit whereas Hyper-CNTF required heterodimerization of the gp130 and LIF-R receptor subunit. We concluded that the fusion protein Hyper-CNTF had superagonistic activity on target cells expressing gp130 and LIF-R, but lacking membrane-bound CNTF-R.

[Study of multi-factor cognition evoked by binocular disparity].

It is the aim of studies in cognitive process to understand how the impressive cognitive capacity of the human mind is uninterruptedly developed and how the process is controlled. We have been focusing attention on the central question with stereoscopic research. A multi-channel EEG data acquisition system is constructed for cognition studies which not only works perfectly in the EEG collection and signal processing of stereoscopic visual evoked potentials(VEP) but also is suitable for investigative and clinical use. We have identified the fact that the processing of stereoscopic depth information is done in the cortical advance functional areas with labeled characteristic signaling of the depth related VEP and the results were shown to be of no difference when compared with the ones of other investigations. We believe, the stereoscopic depth cognition is both a dynamic multi-factor processing process and a consequence of depth perception in advanced cortical areas through biological feedback to the whole process of visual signal processing. It is our novel and significant supposition in the psychophysical study, and the experimental results of the VEP are presented in this article.

The effect of gp130 stimulation on glutamate-induced excitotoxicity in primary hippocampal neurons.

Primary hippocampal neurons from newborn rats treated with glutamate showed clear excitotoxicity. This excitotoxicity could be reversed by treatment of the cells with cytokines of the interleukin-6 family. Stimulation of gp130 on hippocampal neurons resulted in tyrosine phosphorylation of STAT3 and activation of p42 and p44 MAP kinases. Receptors for the interleukin-6 type cytokines are active in membrane bound and soluble form. To address the question whether the neurotrophic effect of interleukin-6 type cytokines requires soluble cytokine receptors we used fusion proteins of interleukin-6 coupled to the soluble interleukin-6 receptor and ciliary neurotrophic factor coupled to the soluble ciliary neurotrophic factor receptor. Ciliary neurotrophic factor was as active as the cytokine-receptor fusion protein, indicating that hippocampal neurons express ciliary neurotrophic factor receptor on the cell surface. In contrast, interleukin-6 was only active at very high concentrations whereas the fusion protein of interleukin-6 coupled to the soluble interleukin-6 receptor (Hyper-IL-6) exhibited high neurotrophic activity at the same concentrations as ciliary neurotrophic factor. These data indicate that interleukin-6 receptor expression is very low on hippocampal neurons and that gp130 stimulation can be used to rescue hippocampal neurons from excitotoxicity.

[Changes of subcellular calcium in hypo-themal-preserved cat kidney cortex cells detected by X-ray microanalysis of microsections].

It was pointed out by many researches that keeping the concentration of Ca2+ in cells could increase the survival rate of hypothermic preserved kidneys and the survival rate of transplants. In this study, changes of the concentration of calcium were detected within catoplasm, mitochondria, endoplasmic reticulum and nucleus in the isolated hypothermic storage cat kidney, Ca2+ be marked with calcium cytochemical probe (K2H2Sb2O7) and detected by X-ray microanalysis of microsections. After 24, 48 and 72 hours preservation, the p/b (peak/back) of calcium within cytoplasm and mitochondria increased significantly. There were no obvious changes within endoplasmic reticulum and nucleus. It demonstrates that the Ca2+ were released from calcium pool (except the endoplasmic reticulum, nucleus, mitochondria etc.) to cytoplasm during preservation; and mitochondria can uptake calcium from cytoplasm to some extent, while the calcium concentration of cytoplasm is higher than normal.