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We aimed to investigate the effects of low-level light emitting diode therapy (LED-T) on the long-term functional outcomes after cerebral ischemia, and the optimal timing of LED-T initiation for achieving suitable functional recovery. Focal cerebral ischemia was induced in mice via photothrombosis. These mice were assigned to a sham-operated (control), ischemic (vehicle), or LED-T group [initiation immediately (acute), 4 days (subacute) or 10 days (delayed) after ischemia, followed by once-daily treatment for 7 days]. Behavioral outcomes were assessed 21 and 28 days post-ischemia, and histopathological analysis was performed 28 days post-ischemia. The acute and subacute LED-T groups showed a significant improvement in motor function up to 28 days post-ischemia, although no brain atrophy recovery was noted. We observed proliferating cells (BrdU+) in the ischemic brain, and significant increases in BrdU+/GFAP+, BrdU+/DCX+, BrdU+/NeuN+, and CD31+ cells in the subacute LED-T group. However, the BrdU+/Iba-1+ cell count was reduced in the subacute LED-T group. Furthermore, the brain-derived neurotrophic factor (BDNF) was significantly upregulated in the subacute LED-T group. We concluded that LED-T administered during the subacute stage had a positive impact on the long-term functional outcome, probably via neuron and astrocyte proliferation, blood vessel reconstruction, and increased BDNF expression. Picture: The rotarod test for motor coordination showed that acute and subacute LED-T improves long-term functional recovery after cerebral ischemia.

To evaluate the question of whether protease activated receptor-1 (PAR-1) antagonist is a potential therapeutic target in multiple sclerosis, we treated experimental autoimmune encephalomyelitis (EAE) mice with two PAR-1 antagonists, KC-A0590 and SCH-530348. Treatment with both antagonists resulted in a significant decrease in the clinical characteristics of EAE mice by suppressing demyelination and infiltration of inflammatory cells in the spinal cord and brain, as well as a significantly reducing the increased thrombin and tumor necrosis factor-α. Profound leakage of dextran was observed in the brain of EAE mice. However, treatment with PAR-1 antagonists resulted in the stabilization of vascular endothelial cells and reduced blood-brain barrier breakdown with suppression of inflammatory response. Treatment with PAR-1 antagonists also resulted in down-regulated expression of matrix metalloproteinase-9 and preserved expression of occludin and zonula occludens (ZO)-1 in the brain and their significant expression was confirmed in neurons, astrocytes, and vascular endothelial cells. Finally, endothelial cells and primary cultured astrocytes were treated with PAR-1 antagonists; both antagonists suppressed thrombin-induced breakdown of ZO-1 in endothelial cells and secretion of matrix metalloproteinase-9 in astrocytes. Collectively, our results suggest that PAR-1 antagonist is effective in attenuation of the clinical symptoms of EAE mice by stabilizing the blood-brain barrier and may have therapeutic potential for treatment of multiple sclerosis.

Scope: While TRAIL is relatively non-toxic to normal cells, it can selectively induce apoptosis in many types of transformed cells. Nevertheless, some non-small cell lung cancer (NSCLC) cells are particularly resistant to the effects of TRAIL. Here, we report that in combination with naringenin exposure to TRAIL induced apoptosis in TRAIL-resistant NSCLC A549 cells with no detectable inhibitory effects on cell proliferation of normal lung fibroblast cells. Methods and results: Cytotoxicity was evaluated by MTT assay. Apoptosis was detected using DAPI staining, and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay. For knockdown of Bid and DR5 expression, Bid and DR5 siRNAs were transfected into cells via lipofection. We could show that following exposure to naringenin, DR5 proteins were up-regulated and knockdown of DR5 expression by siRNA attenuated naringenin plus TRAIL-induced apoptosis. Naringenin and TRAIL effectively induced Bid cleavage and siRNA-mediated silencing of Bid reduced the sensitizing effect of naringenin. Furthermore, co-treatment with naringenin and TRAIL resulted in reduction of the clonogenic capacity of A549 cells, and surviving clones could be re-sensitized for repeated TRAIL treatment. Conclusion: Our results indicate that treatment with a combination of TRAIL and naringenin may be a safe strategy for treatment of resistant NSCLC.

Bioassay-guided fractionation of Curcuma longa by solvent partitioning and purification with octadecylsilane open column chromatography yielded a partial purification. The active 80% methanol chromatographic fraction from the ethyl acetate layer [partial purification from C. longa (PPC)] was used to investigate the alpha-melanocyte-stimulating hormone (alpha-MSH)-stimulated melanogenesis signal pathway in B16F10 cells. In cells stimulated alpha-MSH, PPC inhibited cellular melanin contents, tyrosinase activity and expression of melanogenesis-related proteins including microphthalmia-associated transcription factor (MITF), tyrosinase and tyrosinase-related proteins (TRP). Melanogenesis-regulating signalling such as mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt was activated by PPC in alpha-MSH-stimulated B16F10 cells. The suppressive activity of PPC on alpha-MSH-induced melanogenesis was abrogated by selective inhibition of MEK/ERK (PD98059) and PI3K (LY294002). MEK/ERK or Akt activation by PPC may contribute to reduced melanin synthesis via MITF and its downstream signal pathway including tyrosinase and TRPs in alpha-MSH-induced melanogenesis.

Cimicifuga rhizoma has long been used in traditional Korean medicine. In particular, a Cimicifuga heracleifolia extract (CHE) was reported to inhibit the formation of glutamate and the glutamate dehydrogenase activity in cultured rat islet. Glutamate activates melanogenesis by activating tyrosinase. Accordingly, it was hypothesized that a CHE might inhibit the melanogenesis-related signal pathways including the inhibition of microphthalmia-associated transcription factor (MITF)-tyrosinase signaling and/or the activation of extracellular signal-regulated kinase (ERK)-Akt signaling. The results showed that CHE inhibits the cellular melanin contents, tyrosinase activity and expression of melanogenesis-related proteins including MITF, tyrosinase and tyrosinase-related protein (TRP)s in alpha-melanocyte-stimulating hormone-stimulated B16 cells. Moreover, CHE phosphorylates MEK, ERK1/2 and Akt, which are melanogenesis inhibitory proteins. The data suggest that CHE inhibits melanogenesis signaling by both inhibiting the tyrosinase directly and activating the MEK-ERK or Akt signal pathways-mediated suppression of MITF and its downstream signal pathway, including tyrosinase and TRPs. Therefore, C. heracleifolia would be a useful therapeutic agent for treating hyperpigmentation and an effective component in whitening and/or lightening cosmetics.

The sustain waveforms are distorted relative to the displayed area. The distorted sustain waveform, especially the last X sustain waveform causes the address time to be delayed. Accordingly, to produce a stable address discharge irrespective of the displayed area, the sustain waveform, especially the last X sustain waveform prior to the selective reset waveform, is compensated by making its rising slope faster in proportion to the displayed area by means of controlling the timing sequence of the energy recovery circuit (ERC) circuit. As a result, the compensated sustain waveform enables the address delayed time to be saturated irrespective of the displayed area.

To explain a non-uniformity of the address discharge during an address period, the wall voltage variation during an address period was investigated as a function of the number of the applied address pulse by the Vt closed curve. It was observed that the wall voltage between the scan and address electrodes was decreased with an increase in the number of the applied address pulse. It was also observed that the wall voltage variation during an address period strongly depends on the voltage difference between the Y and A electrodes.

Background: Although environmental conditions can influ- ence the expression of glycoconjugates (GCs) in the epidermis and cutane- ous gland of amphibians, seasonal features regarding GCs in frogs have rarely been studied. In the present study, we report the seasonal varia- tions of the integumental GCs in Rana rugosa. Methods: GCs were investigated at the light microscopic level using conventional and lectin histochemistry. Results: During the pre- through posthibernating periods, stronger periodic acid-Schiff (PAS)-positive GCs were observed in the stratum corneum and transitional layer of the epidermis. At the same time, alcian blue and PAS-positive GCs filled the lumen of the mucous gland. The affinity for PNA in the transitional layer, UEA-1 in stratum germinativum, and SBA in the mucous glands increased significantly during the same periods. In addition, new GCs, which are specific for SBA in the stratum corneum, BSL-1, RCA-1, sWGA, and LCA in some cells of the transitional layer, were detected. Conclusions: Elevated GCs and a diversity of lectin affinities may be a result of seasonal adaptations related to hibernation. An affinity for PNA, UEA-1, and SBA in the frog skin may be useful as a marker of seasonal changes. Anat. Rec. 249:24-31, 1997. r 1997 Wiley-Liss, Inc.

The negative falling voltage during the reset-period affects the power consumption as well as the statistical delay time during the subsequent address period. In the PDP without MgO single-crystal powder, the negative falling reset voltage should be increased in the negative direction to minimize the statistical delay time, whereas in the PDP with MgO single-crystal powder, the negative falling reset voltage can be adjusted to minimize the power consumption thanks to the improvement of the statistical delay characteristics. As a result of adjusting the negative falling voltage in the 50-inch FHD PDP with MgO single-crystal powder, the consumed power and background luminance decreased about by 8.1 % and 33 % for the full black pattern, respectively. for the full-white pattern, the consumed power was reduced about by 5.6 % and the luminous efficiency was improved about by 3.5 %.

The sustain waveforms are distorted relative to the displayed area. The sustain waveforms are distorted relative to the displayed area, which causes the variations in luminance and luminous efficiency. It is found that the constant rising slope of the displayed are causes the sustain waveform distortion. A discharge in a cell has voltage-current (V-I) characteristics that the applied voltage waveform determines the discharge current. A circuit also has V-I characteristics that the total current of all cells determines the voltage waveforms applied to cells. Furthermore, the Y and X electrode have resistance and belong to cells aligned horizontally, accordingly, the number of on-cells in horizontal line distorts the voltage applied to each cell. This paper shows by analysis and experiments that the applied voltage and the luminance and the luminous efficiency of an AC-PDP cell are affected by the amount and distribution of displayed area.

This paper proposes a modified selective reset driving waveform that can lower the potential difference between the scan and address electrodes by applying the address-bias voltage (Va-bias) to the address electrode during the application of the rising pulse of Y-electrode in the selective reset-period. This address-bias voltage (Va-bias) plays a role in suppressing the wall-charge accumulation on the address electrode during the selective reset-period, thereby contributing to minimizing the wall-voltage variation during the address-period and as such allowing the higher voltage difference (=ΔVy) between the scan low voltage (Vsl) and the negative falling ramp voltage (Vnf) during an address-period without any misfiring discharge. When adopting the proposed selective reset waveform, the address discharge delay time is observed to be reduced by about 120 ns.

A new negative sustain waveform is proposed to improve the sustain and address discharge characteristics of PDP. The effects of conventional positive and proposed negative sustain waveforms on the sustain and address discharge characteristics are examined and compared in the 7-in. test panel with a Ne-Xe (4 %), gas mixture at 100 kHz. In the case of adopting the proposed negative sustain waveform, the luminance and luminous efficiency were improved by about 10 % and 16 %, respectively.