The regulatory role of cyclic nucleotides in the expression of neutrophil responses has been examined. fMLP-stimulated superoxide production in neutrophils was inhibited by dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), histamine, adenosine + theophylline, cAMP elevating agents, and 8-bromoguanosine 3' ,5' -cyclic monophosphate (8-BrcGMP) and sodium nitroprusside, cGMP elevating agents. Staurosporine, a protein kinase C inhibitor, genistein, a protein tyrosine kinase inhibitor and chlorpromazine, a calmodulin inhibitor, inhibited superoxide production by fMLP, but they did not further affect the action of DBcAMP on the stimulatory action of fMLP. DBcAMP, histamine, adenosine+theophylline and genistein inhibited myeloperoxidease release evoked by fMLP, whereas BrcGMP, sodium nitroprusside and staurosporine did not affect it. The elevation of $[Ca^{2+}]_i$ evoked by fMLP was inhibited by genistein and chlorpromazine but was not affected by staurosporine. DBcAMP exerted little effect on the initial peak in $[Ca^{2+}]_i$ response to fMLP but effectively inhibited the sustained rise. On the other hand, BrcGMP significantly inhibited both phases. fMLP-induced $Mn^{2+}$ influx was inhibited by either DBcAMP or BrcGMP. These results suggest that fMLP-stimulated neutrophil responses may be regulated by cAMP more than cGMP. cAMP and cGMP appear not affect stimulated responses by direct protein kinase C activation. Their regulatory action on the stimulated neutrophil responses may be not influenced by other activation processes.
The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure $(BP{\ge}150\;mmHg),$ and 4) SHR with normotensive BP $({\le}150\;mmHg).$ The lower limit of CBF autoregulation in SHR shifted to a higher BP $(82.8{\pm}9.3\'mmHg,\;P<0.05)$ than that in SDR $(58.9{\pm}5.7\;mmHg)$. In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin $(3{\times}10^{-7}\;M)$ was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were $12.5{\pm}1.4\;and\;9.8{\pm}2.8\;fmole/mm^2/60\;min\;(P<0.05)$, while those from SDR and WR were $25.5{\pm}3.1\;and\;24.6{\pm}3.1\;fmole/mm^2/60\;min,$ respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.
Park, Su-Hyung;Chang, Jun;Yang, Se-Hwan;Kim, Hye-Ju;Kwak, Hyun-Hee;Kim, Byong-Moon;Lee, Sung-Hee;Sung, Young-Chul
IMMUNE NETWORK
/
제7권4호
/
pp.186-196
/
2007
Background: Although IL-12 has been widely accepted to playa central role in the control of pathogen infection, the use of recombinant IL-12 (rIL-12) as a vaccine adjuvant has been known to be ineffective because of its rapid clearance in the body. Methods: To investigate the effect of sustained release of IL-12 in vivo in the peptide and protein vaccination models, rIL-12 was encapsulated into poly ($A_{DL}$-lactic-co-glycolic acid) (PLGA). Results: We found that codelivery of IL-12-encapsulated microspheres (IL-12EM) could dramatically increase not only antibody responses, but also antigen-specific $CD4^+\;and\;CD8^+$ T cell responses. Enhanced immune responses were shown to be correlated with protective immunity against influenza and respiratory syncytial virus (RSV) virus challenge. Interestingly, the enhancement of $CD8^+$ T cell response was not detectable when $CD4^+$ T cell knockout mice were subjected to vaccination, indicating that the enhancement of the $CD8^+$ T cell response by IL-12EM is dependent on $CD4^+$ T cell "help". Conclusion: Thus, IL-12EM could be applied as an adjuvant of protein and peptide vaccines to enhance protective immunity against virus infection.
The effect of diazoxide, a $K^{+}$channel opener, on apoptotic cell death was investigated in HepG2 human hepatoblastoma cells. Diazoxide induced apoptosis in a dose-dependent manner and this was evaluated by flow cytometric assays of annexin-V binding and hypodiploid nuclei stained with propidium iodide. Diazoxide did not alter intracellular $K^{+}$concentration, and various inhibitors of $K^{+}$channels had no influence on the diazoxide-induced apoptosis; this implies that $K^{+}$channels activated by diazoxide may be absent in the HepG2 cells. However, diazoxide induced a rapid and sustained increase in intracellular $Ca^{2+}$ concentration, and this was completely inhibited by the extracellular $Ca^{2+}$ chelation with EGTA, but not by blockers of intracellular $Ca^{2+}$ release (dantrolene and TMB-8). This result indicated that the diazoxide-induced increase of intracellular $Ca^{2+}$ might be due to the activation of a Ca2+ influx pathway. Diazoxide-induced $Ca^{2+}$ influx was not significantly inhibited by either voltage-operative $Ca^{2+}$ channel blockers (nifedipinen or verapamil), or by inhibitors of $Na^{+}$, $Ca^{2+}$-exchanger (bepridil and benzamil), but it was inhibited by flufenamic acid (FA), a $Ca^{2+}$-permeable nonselective cation channel blocker. A quantitative analysis of apoptosis by flow cytometry revealed that a treatment with either FA or BAPTA, an intracellular $Ca^{2+}$ chelator, significantly inhibited the diazoxide-induced apoptosis. Taken together, these results suggest that the observed diazoxide-induced apoptosis in the HepG2 cells may result from a $Ca^{2+}$ influx through the activation of $Ca^{2+}$-permeable non-selective cation channels. These results are very significant, and they lead us to further suggest that diazoxide may be valuable for the therapeutic intervention of human hepatomas.
A case study of mesoscale snowfall with polar low signature during 25~26 December 2010 in South Korea is presented. The data used for analysis include surface and upper level weather charts, rain gauge, sea surface temperature, satellite imagery, sounding, and global $1^{\circ}{\times}1^{\circ}$ reanalysis data. The system initiated with a surface trough near the bay of Bohai but quickly intensified to become a polar low within 12 hours. The polar low moved southeastward bringing snowfall to southwestern Korea. There was strong instability layer beneath 800 hPa but baroclinicty was weak and disappeared as the low progressed onto land. Shortwave at 500 hPa and the surface trough became in-phase which hindered the development of the polar low while it approached Korea. However, there were strong tropopause folding (~500 hPa) and high potential vorticity (PV), which allowed the system to maintain its structure and dump 20.3 cm of snow in Jeonju. Synoptic, thermodynamic, dynamic, and moisture analyses reveal that polar low developed in an area of baroclinicity with strong conditional instability and warm air advection at the lower levels. Further, the development of a surface trough to polar low was aided by tropopause folding with PV advection in the upper level, shortwave trough at 500 hPa, and moisture advection with low-level jet (LLJ) of 15 m $s^{-1}$ or more at 850 hPa. Maximum snowfall was concentrated in this region with convection being sustained by latent heat release.
The purpose of this study was to evaluate the effects of the pain management education on pain of the terminal cancer patients at home. For evaluating the effectiveness of the intervention modified Patient Outcome Questionnaire (APS, 1995) including patients concerns with cancer pain management, pain intensity, and interference of daily activities related to pain were measured before and after the education in control group and experimental group and the differences were compared with each other. Satisfaction with pain management was measured after the intervention. Pain management education was delivered to 16 experimental group patients by home care nurses, who were provided with 3-hour education on cancer pain management by one of the researchers. Pain management education included common misconceptions about cancer pain control and pharmacological and non-pharmacological interventions and emphasis was put on the importance of pain reports and patients' active participation in pain management. The results of the study were as follows. Patients concerns with pain management were decreased more greatly in the experimental group than those of the control group. The worst, average, and present pain intensities during the last 24 hours were decreased more greatly in the experimental group, and total score and each subcategory of the interference of daily living, except walking, were decreased more greatly in the experimental group. And satisfaction score with total pain management and nurses response to the pain reports were higher in the experimental group. The results of this study suggest that pain management education given to the patients by home care nurses is a very useful intervention to improve pain of the cancer patients at home. This positive result is thought to derive from patients' active pain report and participation in pain control and the use of powder form sustained release morphine for breakthrough pain control in part. Further studies with increased sample size from more institutions are recommended and early introduction of short acting morphine is strongly suggested for effective cancer pain control.
Alpha-pinene is an organic compound that possesses antibiotic and anti-parasitic activities. In this study, we developed a layered nanocomposite to combat against Miamiensis avidus which causes scuticociliatosis in the olive flounder Paralichthys olivaceus. We used a solid-solid reaction to develop the layered nanocomposite, incorporating-pinene ($C_{10}H_{16}$) into organically modified montmorillonite. We used cetyltrimethylammonium cations as the interlayered modifier for the adsorption of hydrophobic pinene molecules. The X-ray diffraction patterns of the nanocomposite structure showed that the basal spacing increased from $9.6{\AA}$ to $30.4{\AA}$. Interestingly, the fraction of ${\alpha}$-pinene released remained constant for a long period of time (228 h) due to the layered nature of the nanocomposite. Additionally, optical microscopic images of the treated scuticociliatids revealed that their cells were lysed, and this effect increased with the increasing concertration of ${\alpha}$-pinene. Histopathological assessment of ${\alpha}$-pinene nanocomposite-treated olive flounder gills revealed no significant morphological changes, even at the highest concentration of the ${\alpha}$-pinene. The nanocomposite has several advantages, including easy handling, high solubility, low toxicity, and the easy formulation of granules or powder, which improve the pesticidal activity of ${\alpha}$-pinene. Collectively, our results suggest that ${\alpha}$-pinene nanocomposite may be a useful treatment against scuticociliatosis.
To explore the possible cancer therapeutic application of "Bo-yang-hwan-oh-tang" (BH), a herbal medicinal recipe used for improvement of blood stasis, we have examined its direct cytotoxicity against tumor cell, and induction of cytotoxic activity of lymphocytes. Water extract of BH alone did not exhibit direct cytotoxicity to Yac-1 target cells even with high concentrations (10 mg/ml). By exposure for 3 days, BH did not induce any nonspecific cytotoxic activity of mouse spleen cells, either, when assessed in a 4 hr $^{51}Cr-release$ assay. However, when BH was added during CD3 stimulation of non-adherent spleen cells, non-specific CTL activity was markedly promoted in a dose dependent manner. In contrast, BH did not alter activated NK cell activity following IL-2 stimulation. These data suggest that BH does not induce but upregulates non-specific CTL effecter function and that activated NK cell does not respond to BH. For elucidation of the mechanism underlying this function of BH, time kinetic study for IL-2 production using ELISA was undertaken. IL-2 production following CD3 stimulation was significantly augmented and higher level of IL-2 is sustained over 3 days in the culture medium by BH treatment. Moreover, addition of exogenous IL-2 during CD3 stimulation resulted in a similar level of cytotoxicity between control and BH-treated culture. These data indicate that the BH-mediated upregulation of non-specific CTL activity is contributed by augmentation of IL-2 production. Our data imply the possible application of BH for combination therapy of cancer with non-specific activator.
Purpose: Chronic infected wounds sustained over 4 weeks with exposed tendon or bone are difficult challenges to plastic surgeons. Vacuum assisted closure (VAC) device has been well used for the management of chronic wounds diminishing wound edema, reducing bacterial colonization, promoting formation of granulation tissue and local blood flow by negative pressure to wounds. But Commercial ready-made VAC device might have some difficulties to use because of its high expenses and heavy weight. So we modified traditional VAC device with silver dressing materials as topical therapeutic agents for control of superimposed bacterial wound infection such as MRSA, MRSE and peudomonas. Methods: We designed the modified VAC device using wall suction, 400 cc Hemovac and combined slow release silver dressing materials. We compared 5 consecutive patients' data treated by commercial ready-made VAC device(Group A) with 11 consecutive patients' data treated by modified VAC device combined with silver dressing materials(group B) from September 2004 to June 2007. Granulation tissue growth, wound discharge, wound culture and wound dressing expenses were compared between the two groups. Results: In comparison of results, no statistical differences were identified in reducing rate of wound size between group A and B. Wound discharge was significantly decreased in both groups. Modified VAC device with silver dressing materials showed advantages of convenience, cost effectiveness and bacterial reversion. Conclusion: In combination of modified VAC device and silver dressing materials, our results demonstrated the usefulness of managing chronic open wounds superimposed bacterial infection, cost effectiveness compared with traditional VAC device and improvement of patient mobility.
We investigated the atomic and electronic properties of graphene grown by Pd silicidation and intercalation using LEED, STM, and ARPES. Pd was deposited on the 6H-SiC(0001) surface at RT. The formation of Pd silicide gives rise to breaking of Si-C bonds of the SiC crystal, which enables to release C atoms at low temperature. The C atoms are transformed into graphene from $860^{\circ}C$ according to the LEED patterns as a function of annealing temperature. Even though the graphene spots were observed in the LEED pattern and the Fourier transformed STM images after annealing at $870^{\circ}C$, the topography images showed various superstructures so that graphene is covered with Pd silicide residue. After annealing at $950^{\circ}C$, monolayer graphene was revealed at the surface. The growth of graphene is not limited by surface obstacles such as steps and defects. In addition, we observed that six protrusions consisting of the honeycomb network of graphene has same intensity meaning non-broken AB-symmetry of graphene. The ARPES results in the vicinity of K point showed the non-doped linear ${\pi}$ band structure indicating monolayer graphene decoupled from the SiC substrate electronically. Note that the charge neutrality of graphene grown by Pd silicidation and intercalation was sustained regardless of annealing temperature in contrast with quasi-free- standing graphene induced by H and Au intercalation. Further annealing above $1,000^{\circ}C$ accelerates sublimation of the Pd silicide layer underneath graphene. This results in appearance of the $(6r3x6r3)R30^{\circ}$ structure and dissolution of the ${\pi}$ bands for quasi-free-standing graphene.
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