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ABSTRACT: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important regulator of the maturation and function of cells in the granulocyte and macrophage lineages, and also plays a significant role in wound healing. In a previous study, we expressed human GM-CSF in rice cells (rice cell-derived human GM-CSF; rhGM-CSF). The purpose of the present study was to evaluate its effect on wound healing in oral mucositis. Oral mucositis was induced in Syrian hamster cheek pouches by 5-fluorouracil treatment and mechanical scratching. Ulcerated areas were treated from days 3 to 14 with an application of 200 µL saline, or of the same volume of a solution containing 0.04, 0.2, or 1 µg/mL rhGM-CSF. Treatment of hamsters with rhGM-CSF reduced the ulcerated areas of the oral mucosa, compared with the control. Early in the healing process, the mucositis tissue layer of the rhGM-CSF-treated group showed significantly decreased myeloperoxidase activity and increased numbers of proliferating cell nuclear antigen (PCNA)-positive cells. Treatment with rhGM-CSF also affected expression of inflammatory cytokines in the ulcerative mucosal tissue. These results demonstrate the efficacy of plant-produced rhGM-CSF in wound healing and have significant implications for the development of rhGM-CSF as a therapeutic agent for ulcerative oral mucositis.
Biological & Pharmaceutical Bulletin 01/2013; 36(3):425-31. · 1.66 Impact Factor
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ABSTRACT: 1. The interactions between herbal dietary supplements and therapeutic drugs have emerged as an important issue and P-glycoprotein (P-gp) has been reported as one of the significant factors of these interactions. 2. The objective of this article is to examine the effects of single and repeated administrations of silymarin on pharmacokinetics of a P-gp substrate, risperidone, and its major metabolite, 9-hydroxyrisperidone, in rats. 3. To determine the plasma levels of risperidone and 9-hydroxyrisperidone in rats, a HPLC method was developed using a liquid-liquid acid back extraction. When risperidone (6 mg/kg) was co-administered with silymarin (40 mg/kg) to rats orally, the C(max) of 9-hydroxyrisperidone was significantly increased to1.3-fold (p < 0.05), while the other pharmacokinetic parameters did not show any significant differences. Expanding the experiment where rats were repeatedly administered with silymarin for 5 days prior to giving risperidone, the C(max) of risperidone and 9-hydroxyrisperidone were significantly increased to 2.4-fold (p < 0.001) and 1.7-fold (p < 0.001), respectively, and the AUC(0-t), as well to 1.7-fold (p < 0.05) and 2.1-fold (p < 0.01), respectively. 4. The repeated exposures of silymarin, compared to single administration of silymarin, increased oral bioavailability and affected the pharmacokinetics of risperidone and 9-hydroxyrisperidone, by inhibiting P-gp.
Xenobiotica 12/2012; · 1.79 Impact Factor
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ABSTRACT: Aging is associated with immune dysfunction and conditions such as inflamm-aging and immunosuppression. Arsenic, an environmental contaminant distributed worldwide, affects the immune system. This study tested the hypothesis that arsenic has distinct effects on T cell proliferation and the production of cytokines by activated T cells. Murine splenocytes from young (2 months) and aged (24-26 months) C57BL/6 mice were exposed to arsenite (As(3+)), the most toxic form of inorganic arsenic, and stimulated with concanavalin A (Con A) or anti-CD3 antibody. T cell proliferation decreased significantly in response to Con A and anti-CD3 at subtoxic doses of arsenite in splenocytes from both young and aged mice. Arsenite, added concurrently with Con A or anti-CD3, significantly inhibited the production of interleukin-2 (IL-2), interferon-γ (IFN-γ), and interleukin-4 (IL-4) by splenocytes from young mice and significantly reduced the production of IL-10 by splenocytes from aged mice. In contrast, the production of IL-2 and IL-4 by splenocytes from aged mice was only slightly affected by arsenite. The results show that arsenic exposure reduces the immune response in splenocytes. Moreover, this effect may be influenced by aging.
Archives of Pharmacal Research 02/2012; 35(2):375-82. · 1.59 Impact Factor
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ABSTRACT: Docetaxel micelle-encapsulated by a tripodal cyclotriphosphazene amphiphilile [NP(PEG750)(GlyPheLeu)(2)Et](3) (CP750) exhibited outstanding drug-loaded micelle stability in aqueous solution compared with the polymeric micelles assembled from linear block copolymers. Furthermore, docetaxel micelle-encapsulated by CP750 is obtainable in solvent free powder form, which is immediately soluble in any aqueous media including saline and PBS and very stable to photo-degradation even in the room light at room temperature. Although docetaxel micelle-encapsulated by CP750 did not display highly improved pharmacokinetic profile compared with Taxotere currently in clinical use, its in vivo xenograft trials exhibited excellent antitumor efficacy by showing complete tumor regression against the breast cancer cells (MDA-MB-231) at a lower dose of 5mg/kg and better efficacy against gastric cancer cells (MKN-28) compared with Taxotere. Furthermore, according to the comparative acute toxicity study, toxicities associated with Taxotere may be remarkably reduced by micelle-encapsulation of docetaxel using CP750, which afforded a much higher LD(50) value of 75 mg/kg compared with 28 mg/kg of docetaxel in Taxotere. Thus docetaxel micelle-encapsulated by CP750 has entered the stage of preclinical studies.
International journal of pharmaceutics 11/2011; 422(1-2):374-80. · 2.96 Impact Factor
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ABSTRACT: Ceramide has been suggested to be not only a tumor-suppressive lipid but also a regulator of phagocytosis. We examined whether exogenous cell-permeable C(6)-ceramide enhances the phagocytic activity of Kupffer cells (KCs) and affects the level of cellular ceramides. Rat KCs were isolated by collagenase digestion and differential centrifugation, using Percoll system. Phagocytic activity was measured by FACS analysis after incubating KCs with fluorescence-conjugated latex beads, and the level of cellular ceramide was analyzed by liquid chromatography tandem-mass spectrometry (LC-MS/MS). In this study we found that permeable C(6)-ceramide increases the cellular levels of endogenous ceramides via a sphingosine-recycling pathway leading to enhanced phagocytosis by KCs.
Molecules and Cells 08/2011; 32(4):325-31. · 2.18 Impact Factor
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Dong Hun Lee,
Sung Hyun Kim,
Kyong Hoon Ahn,
Seok Kyun Kim, Jong Min Choi,
Jung Eun Ji,
Jong Hoon Won,
Yang Hui Park,
Chaemin Lim,
Sanghee Kim,
Dae Kyong Kim
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ABSTRACT: Sphingomyelinase catalyzes the hydrolysis of sphingomyelin to generate ceramide, an important molecule involved in the regulation of various cellular responses. In this study, we partially purified the neutral sphingomyelinase2 (nSMase2) and identified the inhibitors, D-lyxophytosphingosine and D-arabino-phytosphingosine, which have an inhibitory effect on nSMase2 in a concentration-dependent manner. A Dixon plot of each phytosphingosines revealed their probable inhibitory pattern, i.e., apparent competitive inhibition. These compounds did not inhibit the Mg(2+)-independent neutral SMase activity, although the known nSMase2 inhibitor, GW4869, showed inhibitory effects on Mg(2+)-independent neutral SMase activity. Further, the two phytosphingosines specifically inhibited the ceramide generation regulated by nSMase2.
Archives of Pharmacal Research 02/2011; 34(2):229-36. · 1.59 Impact Factor
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ABSTRACT: Ceramide has been suggested to function as a mediator of exocytosis in response to the addition of a calcium ionophore from PC12 cells. Here, we show that although cell-permeable C(6)-ceramide or a calcium ionophore alone did not increase either the degranulation of serotonin or the release of arachidonic acid (AA) from RBL-2H3 cells, their combined effect significantly stimulated these processes in a time- and dose-dependent manner. This effect was inhibited by the presence of an exogenous calcium chelator and significantly suppressed by the CERK inhibitor (K1) and phospholipase A(2) (PLA(2)) inhibitors. Moreover, cytosolic PLA(2) GIVA (cPLA(2) GIVA) siRNA-transfected RBL-2H3 cells showed a lower level of serotonin release than scramble siRNA-transfected cells. Little is known about the regulation of degranulation proximal to the activation of cytosolic phospholipase A(2) GIVA, the initial rate-limiting step in RBL-2H3 cells. In this study, we suggest that CERK, ceramide-1-phosphate, and PLA(2) are involved in degranulation in a calcium-dependent manner. Inhibition of p44/p42 mitogen-activated protein kinase partially decreased the AA release, but did not affect degranulation. Furthermore, treatment of the cells with AA (ω-6, C20:4), not linoleic acid (ω-6, C18:2) or α-linolenic acid (ω-6, C18:3), induced degranulation. Taken together, these results suggest that ceramide is involved in mast cell degranulation via the calcium-mediated activation of PLA(2).
Prostaglandins & other lipid mediators 01/2011; 94(3-4):88-95. · 2.70 Impact Factor
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ABSTRACT: Ceramide serves as a second messenger produced from sphingomyelin by the activation of sphingomyelinase (SMase). Here, we suggest that neutral SMase 2 (nSMase2) may regulate dopamine (DA) uptake. nSMase2 siRNA-transfected PC12 cells showed lower levels of nSMase activity and ceramide than scramble siRNA-transfected and control cells. Interestingly, transfection of nSMase2 siRNA or pretreatment with the nSMase2-specific inhibitor GW4869 resulted in decreased DA uptake. Reciprocally, exposure of PC12 cells to cell-permeable C(6)-ceramide induced a concentration-dependent increase in DA uptake. Removal of extracellular calcium by EGTA increased DA uptake in scramble-transfected and control cells, but not in nSMase2 siRNA-transfected or GW4869-pretreated cells. Moreover, siRNA-transfected cells showed higher levels of intracellular calcium than scramble cells, while C(6)-ceramide treatment resulted in decreased intracellular calcium compared to vehicle treatment alone. Taken together, these data suggest that nSMase2 may increase DA uptake through inducing ceramide production and thereby decreasing intracellular calcium levels.
Cellular signalling 05/2010; 22(5):865-70. · 4.09 Impact Factor
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ABSTRACT: 3-Nitropropionic acid (3-NP) induces hearing loss by impairing mitochondrial energy generation. Geranylgeranylacetone (GGA) is known to protect the cochlea from various injuries. The present study was designed to investigate the protective effect of GGA against acute 3-NP-induced damage to the cochlear mitochondria. Female Hartley guinea pigs were divided into 4 groups. The 3-NP vehicle was injected to control animals and in animals receiving GGA alone, only GGA was administered for 7 days. 3-NP (500 mM, 4 microl) was administered with (animals receiving both GGA and 3-NP) or without (animals receiving 3-NP alone) GGA pretreatment (800 mg/kg, 7 days). The auditory brainstem response (ABR) was recorded at click and at 8, 16 and 32 kHz before and after injection, respectively. After cochlear harvest, hematoxylin/eosin staining and immunohistochemistry for anti-HSP70 antibody were done. 3-NP exposure resulted in elevated ABR thresholds that exceeded the maximum recording limit, while GGA pretreatment before 3-NP exposure led to a significant decrease in hearing threshold shift. Histological analysis of above former group revealed loss of type II fibrocytes in the spiral ligament, hair cells in the organ of Corti, stellate fibrocytes in the spiral limbus and spiral ganglion cells, while in above latter group, these cells were preserved. Control animals revealed weak HSP70 expression in the nuclei of some supporting cells (pillar cells, Deiters' cells and Hensen's cells) and interdental cells. Animals receiving GGA alone showed strong HSP70 expression in the same area as in control animals, while animals receiving both GGA and 3-NP demonstrated slightly decreased HSP70 expression in that area. These results suggest that GGA may protect the cochlea against acute injury resulting from mitochondrial dysfunction.
NeuroToxicology 03/2010; 31(3):317-25. · 3.10 Impact Factor
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ABSTRACT: Cellular hypoxia can lead to cell death or adaptation and has important effects on development, physiology, and pathology. Here, we investigated the role and regulation of ceramide in hypoxia-induced apoptosis of SH-SY5Y neuroblastoma cells. Hypoxia increased the ceramide concentration; subsequently, we observed biochemical changes indicative of apoptosis, such as DNA fragmentation, nuclear staining, and poly ADP-ribose polymerase (PARP) cleavage. The hypoxic cell death was potently inhibited by a caspase inhibitor, zVAD-fmk (benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone). l-Cycloserine, a serine palmitoyltransferase (SPT) inhibitor, and fumonisin B(1) (FB(1)), a ceramide synthase inhibitor, inhibited the hypoxia-induced increase in ceramide, indicating that the increase occurred via the de novo pathway. Hypoxia increased the activity and protein levels of SPT2, suggesting that the hypoxia-induced increase in ceramide is due to the transcriptional up-regulation of SPT2. Specific siRNA of SPT2 prevented hypoxia-induced cell death and ceramide production. However, hypoxia also increased the cellular level of glucosylceramide, which was inhibited by a glucosylceramide synthase (GCS) inhibitor and specific siRNA, but not a ceramidase inhibitor. The increase in glucosylceramide was accompanied by increases in both PARP cleavage and DNA fragmentation. Together, the current results suggest that both SPT and GCS may regulate the cellular level of ceramide, and thus may be critical enzymes for deciding the fate of the cells exposed to hypoxia.
Cellular signalling 11/2009; 22(4):610-8. · 4.09 Impact Factor
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ABSTRACT: Nonintrusive monitoring of a driver's physiological signals was introduced and evaluated in a car as a test of extending the concept of ubiquitous healthcare to vehicles. Electrocardiogram, photoplethysmogram, galvanic skin response, and respiration were measured in the ubiquitous healthcare car (U-car) using nonintrusively installed sensors on the steering wheel, driver's seat, and seat belt. Measured signals were transmitted to the embedded computer via Bluetooth(R) communication and processed. We collected and analyzed physiological signals during driving in order to estimate a driver's stress state while using this system. In order to compare the effect of stress on physical and mental conditions, two categories of stresses were defined. Experimental results show that a driver's physiological signals were measured with acceptable quality for analysis without interrupting driving, and they were changed meaningfully due to elicited stress. This nonintrusive monitoring can be used to evaluate a driver's state of health and stress.
Telemedicine and e-Health 04/2009; 15(2):182-9. · 1.42 Impact Factor
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ABSTRACT: The purpose of this study was to develop an unobtrusive energy expenditure (EE) measurement system using an infrared (IR) sensor-based activity monitoring system to measure indoor activities and to estimate individual quantitative EE. IR-sensor activation counts were measured with a Bluetooth-based monitoring system and the standard EE was calculated using an established regression equation. Ten male subjects participated in the experiment and three different EE measurement systems (gas analyzer, accelerometer, IR sensor) were used simultaneously in order to determine the regression equation and evaluate the performance. As a standard measurement, oxygen consumption was simultaneously measured by a portable metabolic system (Metamax 3X, Cortex, Germany). A single room experiment was performed to develop a regression model of the standard EE measurement from the proposed IR sensor-based measurement system. In addition, correlation and regression analyses were done to compare the performance of the IR system with that of the Actigraph system. We determined that our proposed IR-based EE measurement system shows a similar correlation to the Actigraph system with the standard measurement system.
Telemedicine and e-Health 12/2008; 14(9):881-8. · 1.42 Impact Factor
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ABSTRACT: A personal computer (PC)-based audiometer was developed for interactive remote audiometry. This paper describes a tele-audiometric system and evaluates the performance of the device when compared with conventional face-to-face audiometry. The tele-audiometric system is fully PC-based. A sound card featuring a high-quality digital-to-analog converter is used as a pure-tone generator. The audiometric programs were developed based on Microsoft Windows in order to maximize usability. Audiologists and their subjects can use the tele-audiometry system as one would utilize any PC application. A calibration procedure has been applied for the standardization of sound levels in the remote system. The performance of this system was evaluated by comparing PC-based audiometry with the conventional clinical audiometry system for 37 subjects. Also, performance of the PC-based system was evaluated during use at a remote site. The PC-based audiometry system estimated the audiometric threshold with an error of less than 2.3 dBSPL. Only 10.7% of the results exhibited an error greater than 5 dBSPL during use at a remote site. The PC-based tele-audiomerty showed acceptable results for use at a remote site. This PC-based system can be used effectively and easily in many locations that have Internet access but no local audiologists.
Telemedicine and e-Health 11/2007; 13(5):501-8. · 1.42 Impact Factor
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ABSTRACT: This paper introduces a new method, bed actigraphy (BACT) for user-friendly sleep-wake monitoring. BACT provides a non-intrusive acquisition of activity data, and in particular does not require that sensors be attached to the subject's body. The system consists of four load-sensing cells supporting the bed, an A/D converter, and a microcontroller with appropriate software. The performance of BACT was compared to that of standard polysomnography (PSG) recordings and wrist-worn actigraphy (ACT). Ten normal volunteers underwent overnight PSG recordings and were examined simultaneously with BACT and ACT. An automatic scoring algorithm scored each 30-s epoch of the BACT recordings for either 'Wake' or 'Sleep.' A sleep specialist manually scored the PSG recordings, and the results were divided into 'Wake' and 'Sleep' categories. The three methods showed a significant correlation when compared with in the contingency test. The mean epoch-by-epoch agreements between the BACT and PSG, ACT and PSG, and BACT and ACT recordings were 95.2, 92.9, and 94.3%, respectively. The mean absolute differences in sleep percentage (SP) between them were 1.8 +/- 0.82, 3.4 +/- 1.45, and 1.9 +/- 1.16 %, respectively. BACT differentiation of the 'Wake' and 'Sleep' stages proved to be sufficiently robust, and its results were comparable to PSG analysis. This finding supports the experimental and clinical value of bed-activity monitoring during sleep.
Medical & Biological Engineering & Computing 02/2007; 45(1):107-14. · 1.88 Impact Factor
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ABSTRACT: Measurement of driver's state is important in both daily healthcare and prevention of car accidents. Existing measurement methods, however, are too complex and uncomfortable to measure for everyday. A nonintrusive biosignal monitoring system is demanded for increasing the accessibility. In this paper, we proposed a nonintrusive measurement system integrated in a vehicle for recording electrocardiographic (ECG) signals and tested the performance of the system. The system consists of dry electrodes attached to the steering wheel and a wireless communication module using a Bluetooth device. ECG signals measured by our system were compared with those by a conventional system employing wet electrodes during real city road driving. Various parameters used for HRV analysis in time and frequency domain showed no significant differences between the two simultaneously measured ECG signals. The result implies the possibility that developed system could have a potential to monitor health information in a vehicle instead of commercial equipments.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2007; 2007:2303-6.
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ABSTRACT: In the military, there are many dangerous, difficult working conditions. Sometimes soldiers have to cope with the enemy and cannot sleep all the day because of overnight training or operation. So the health state of serviceperson has been the main concern of the commander. Despite the importance, to monitor the health condition of the serviceperson without influence of daily schedule or combat situation is very difficult, because there are so many artifact sources in the field. And the devices which monitor the subjects need the additional work and subjects need to be very careful doing something with devices. We intend to develop the system that can monitor the soldier's biomedical signal unconstrainedly. In this paper we introduce the prototype of our helmet based system. This system measured the ECG, EOG and Eye Blink successfully.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2007; 2007:359-62.
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ABSTRACT: We could get valuable information about various diseases by analyzing urine of patients. For the diabetics, it has been very important to know the glucose concentration in their urine. Until now, there have been many methods to estimate the concentration but they were invasive and annoyed patients. The low-resolution Raman spectroscopy (LRRS) could be an alternative method to be non-invasive and unconscious for patients who want to check the amount of their urine components. LRRS is not expensive and smaller than laboratory Raman spectroscope. And we want to attach it to the common toilet bowl. For the reason, we got the spectrum of diluted urine and predicted the glucose concentration. In addition, we tried to find very small amount of glucose. LRRS was adequate for measuring Raman signal of diluted urine and could find very small amount of glucose. This system will realize the observation of one's health condition every day without awareness
Engineering in Medicine and Biology Society, 2005. IEEE-EMBS 2005. 27th Annual International Conference of the; 02/2006
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ABSTRACT: Mobile telecardiology has been considered one of the successful m-health applications. Recently, the rapid development in mobile technologies enabled corresponding advances in mobile telecardiology applications. The compression issues of Bluetooth enable mobile telecardiology system. We address the relevant hardware design issues and performance
Broadband Networks, 2005. BroadNets 2005. 2nd International Conference on; 11/2005
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ABSTRACT: We could get valuable information about various diseases by analyzing urine of patients. For the diabetics, it has been very important to know the glucose concentration in their urine. Until now, there have been many methods to estimate the concentration but they were invasive and annoyed patients. The Low-Resolution Raman Spectroscopy (LRRS) could be an alternative method to be non-invasive and unconscious for patients who want to check the amount of their urine components. LRRS is not expensive and smaller than laboratory Raman spectroscope. And we want to attach it to the common toilet bowl. For the reason, we got the spectrum of diluted urine and predicted the glucose concentration. In addition, we tried to find very small amount of glucose. LRRS was adequate for measuring Raman signal of diluted urine and could find very small amount of glucose. This system will realize the observation of one's health condition every day without awareness.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2005; 2:1991-3.
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INTERSPEECH 2004 - ICSLP, 8th International Conference on Spoken Language Processing, Jeju Island, Korea, October 4-8, 2004; 01/2004
