• Toxicological Research
• /
• v.14 no.3
• /
• pp.393-400
• /
• 1998

As a series of safety studies on DA-3585, a recombinant human erythropoietin, its local irritancy was examined in rabbits after the following treatments; application into the conjunctival sac of the eye(single), subcutaneous injection (single and -day repeated)and intravenous injection (7-day repeated.)In addition, perivascular irritation of DA-3585 was investigated in mice. In the result of ocular irritation test, 10,000IU/ml solution of DA-3585 could be considered as a non-irritating material. The local irritation of DA-3585 by a single and 7-day repeated subcutaneous injection was negligible and not so much different from that of saline. In the vascular irritancy test, macro-and microscopic observations revealed that local irritation of DA-3585 was comparable to that of saline when injected into retroauricular vein of rabbits for 7 consecutive days. Furthermore the perivascular administration of DA-3585 upto the concentration of 10,000 IU/ml did not induce any morphological abnormalities at injection sites. The results obtained from the present study suggest that the local irritancy of DA-3585 is not different from that of saline when injected through intravenous or subcutaneous route for clinical practice.

• Journal of Pharmaceutical Investigation
• /
• v.40 no.spc
• /
• pp.75-82
• /
• 2010

Specific diseases like cancer and acquired immune deficiency syndrome (AIDS) occur at various organs including lymphatics and spread through lymphatic system. Thus, if therapeutic agents for such diseases are more distributed or targeted to lymphatic system, we can obtain several advantages like reduction of systemic side effect and increase of efficacy. For these reasons, much interest has been focused on the nature of lymphatics and a lot of studies for lymphatic delivery of drugs have been carried out. Because lymphatics consist of single layer endothelium and have high permeability compared with blood capillaries, especially, the studies using nano-sized carriers have been performed. Polymeric nano-particle, liposome, and lipid-based vehicle have been adopted for lymphatic delivery as carriers. According to the administration route and the kind of carrier, the extent of lymphatic delivery efficiency of nano-sized carriers has been changed and influenced by several factors such as size, charge, hydrophobicity and surface feature of carrier. In this review, we summarized the key factors which affect lymphatic uptake and the major features of carriers for achieving the lymphatic delivery. Lymphatic delivery of drug using nano-sized carriers has many fold improved ability of lymphatic delivery compared with that of conventional dosage forms, but it has not shown whole lymph selectivity yet. Even though nano-sized carriers still have the potential and worth to study as lymphatic drug delivery technology as before, full understanding of delivery mechanism and influencing factors, and setting of pharmacokinetic model are required for more ideal lymphatic delivery of drug.

• Proceedings of the Korean Society for Applied Microbiology Conference
• /
• 2003.06a
• /
• pp.55-62
• /
• 2003

The mucosal immune system provides a first line of defense against invasion of infectious agents via inhalation, ingestion and sexual contact. For the induction of protective immunity at these invasion sites, one must consider the use of the CMIS, which interconnects inductive tissues, including PP and NALT, and effector tissues of the intestinal, respiratory and genitourinary tracts. In order for the CMIS to induce maximal protective mucosal immunity, co-administration of mucosal adjuvant or use of mucosal antigen delivery vehicle has been shown to be essential. When vaccine antigen is administered via oral or nasal route, antigen-specific Th 1 and Th2 cells, cytotoxic T lymphocytes(CTLs) and IgA B cell responses are effectively induced by the CMIS. In the early stages of induction of mucosal immune response, the uptake of orally or nasally administered antigens is achieved through a unique set of antigen-sampling cells, M cells located in follicle-associated epithelium(FAE) of inductive sites. After successful uptake, the antigens are immediately processed and presented by the underlying DCs for the generation of antigen-specific T cells and IgA committed B cells. These antigen-specific lymphocytes are then home to the distant mucosal effector tissues for the induction of antigen-specific humoral(e.g., IgA) and cell-mediated (e.g., CTL and Th1) immune responses in order to form the first line of defense. Elucidation of the molecular/cellular characteristics of the immunological sequence of mucosal immune response beginning from the antigen sampling and processing/presentation by M cells and mucosal DCs followed by the effector phase with antigen-specific lymphocytes will greatly facilitate the design of a new generation of effective mucosal antigen-specific lymphocytes will greatly facilitate the design of a new generation of a new generation of effective mucosal adjuvants and of a vaccine deliver vehicle that maximizes the use of the CMIS.

• Atmosphere
• /
• v.22 no.1
• /
• pp.13-28
• /
• 2012

The $PM_{10}$ concentration data is useful for indentifying intensity and a transport way of Asian dust. However, it is difficult to identify them properly due to the limited spatial resolution and coverage. Therefore, a methodology to estimate $PM_{10}$ concentration using visibility data obtained from synoptic observation was developed. To derive the converting function, correlation between visibility and $PM_{10}$ concentration is investigated using visibility and $PM_{10}$ concentration data observed at 20 stations in Korea from 2005 to 2009. To minimize bias due to atmospheric moisture, data with higher relative humidity over a critical value were eliminated while deriving $PM_{10}$-visibility relationship. As a result, an exponentially decreasing function of visibility is obtained under the condition that relative humidity is less than 82%. Verification of the visibility converting function to $PM_{10}$ concentration was carried out for the dust cases in 2010. It was found that spatial distributions of $PM_{10}$ calculated by visibility are in good agreement with the observed $PM_{10}$ distribution, especially for the strong dust cases in 2010. And correlation between the derived and observed $PM_{10}$ concentration was 0.63. We applied the function to obtain distributions of $PM_{10}$ concentration over North Korea, in which concentration data are not available, and compared them with satellite derived dust index, IODI distributions for dust cases in 2010. It is shown that the visibility function estimates quite similar patterns of dust concentration with IODI image, which suggests that it can contribute for prediction by indentifying transport route of Asian dust.

• Archives of Plastic Surgery
• /
• v.33 no.5
• /
• pp.621-626
• /
• 2006

Purpose: Erythropoietin is traditionally known to regulate erythropoiesis, but recently its protective effect against ischemia-reperfusion injury has been studied mainly in cardiovascular and neuronal systems. This study was planned to investigate the effects of recombinant human erythropoietin on ischemia-reperfusion injury in rat TRAM flap model. Methods: Superiorly based TRAM flap was elevated and ischemic insult was given for four hours. Thirty minutes before reperfusion, single dose recombinant human Erythropoietin(5000IU/kg) was injected via intraperitoneal route in the treatment group. At 24 hours postoperatively, systemic neutrophil count, tissue myeloperoxidase activity, malonyldialdehyde amount, nitric oxide content, tissue water content and histologic finding of inflammation was evaluated. On 10 days postoperatively, flap survival rate, angiogenesis and change in hematocrit level was evaluated. Results: Tissue nitric oxide level was significantly higher and myeloperoxidase activity was significantly lower in the treatment group 24 hours after reperfusion. Tissue water content was significantly lower in the treatment group. Perivascular neutrophil infiltration and intravascular adhesion was marked in the control group. Mean flap survival after ten days was 69% in the treatment group, and 47% in the control group, demonstrating a significant difference. Neovascularization in the treatment group also outnumbered the control group. No significant hematocrit rise was noted ten days after erythropoietin administration. Conclusion: Recombinant human Erythropoietin improved flap survival in ischemia-reperfusion injured rat TRAM flaps, at least partially owing to suppressed inflammation, increased nitric oxide, and enhanced angiogenesis.

• Development and Reproduction
• /
• v.14 no.1
• /
• pp.35-41
• /
• 2010

Mammalian reproduction is regulated by a feedback circuit of the key reproductive hormones such as GnRH, gonadotropin and sex steroids on the hypothalamic-pituitary-gonadal axis. In particular, the onset of female puberty is triggered by gain of a pulsatile pattern and increment of GnRH secretion from hypothalamus. Previous studies including our own clearly demonstrated that genistein (GS), a phytoestrogenic isoflavone, altered the timing of puberty onset in female rats. However, the brain-specific actions of GS in female rats has not been explored yet. The present study was performed to examine the changes in the activities of GnRH neurons and their neural circuits by GS in female rats. Concerning the drug delivery route, intracerebroventricular (ICV) injection technique was employed to eliminate the unwanted actions on the extrabrain tissues which can be occurred if the testing drug is systemically administered. Adult female rats (PND 100, 210-230 g BW) were anaesthetized, treated with single dose of GS ($3.4{\mu}g$/animal), and sacrificed at 3 hrs post-injection. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). ICV infusion of GS significantly raised the transcriptional activities of enhanced at puberty1 (EAP-1, p<0.05), glutamic acid decarboxylase (GAD67, p<0.01) which are known to modulate GnRH secretion in the hypothalamus. However, GS infusion could not change the mRNA level of nitric oxide synthase 2 (NOS-2). GS administration significantly increased the mRNA levels of KiSS-1 (p<0.001), GPR54 (p<0.001), and GnRH (p<0.01) in the hypothalami, but decreased the mRNA levels of LH-$\beta$ (p<0.01) and FSH-$\beta$ (p<0.05) in the pituitaries. Taken together, the present study indicated that the acute exposure to GS could directly activate the hypothalamic GnRH modulating system, suggesting the GS's disrupting effects such as the early onset of puberty in immature female rats might be derived from premature activation of key reproduction related genes in hypothalamus-pituitary neuroendocrine circuit.

• The Korean Journal of Pain
• /
• v.19 no.1
• /
• pp.87-90
• /
• 2006

Background: There are many ways to provide superior analgesia for postoperative pain after abdominal surgery of which epidural analgesics with opioids and local analgesics are the most useful. In an effort to maximize the level of analgesia and to minimize the side effects, ketamine, midazolam, clonidine, and adrenalin can be co-administrated as an adjuvant. This study examined the analgesic effect and side effects of midazolam compared with those given an epidural injection of bupivacaine, fentanyl and ketamine. Methods: In a double blind randomized controlled trial, 50 patients received either fentanyl $0.3{\mu}g/kg/h$ and ketamine 0.1 mg/kg/h (Group FK) or fentanyl $0.3{\mu}g/kg/h$, ketamine 0.1 mg/kg/h and midazolam 0.4 mg/h (Group FKM), added to 0.125% of bupivacaine at a rate of as much as 2 ml/h, for patient controlled epidural analgesia (PCEA) after low abdominal surgery. Ten minutes before surgery, the patients received either 10 ml of 0.125% bupivacaine with 0.5 mg/kg of ketamine or 10 ml of 0.125% bupivacaine with the same amount of normal saline, added to fentanyl $50{\mu}g$. The pain score and the side effects were recorded at 1, 3, 6, and 24 hours after surgery. Results: There was no difference in the pain score except for the VAS on coughing 1 hour after surgery. FKM group had fewer side effects. Conclusions: There was a better analgesic effect and fewer side effects with the addition of epidural midazolam to bupivacaine and fentanyl with ketamine formula. However, more study on the dose and route of administration will be needed.

• Journal of Pharmaceutical Investigation
• /
• v.25 no.1
• /
• pp.55-62
• /
• 1995

W/O and O/W emulsions of tegafur (50 mg/5 ml/kg) were orally administered to rats to compare with their mesenteric lymphatic delivery effects. And also in order to demonstrate the lymph targeting associated to the oral route, it was deemed necessary to investigate the fate of solution after oral administration as a control. Lymph and plasma samples were periodically taken from each subject of mesenteric lymphatic duct cannulated rats. Then, lymph and plasma levels of tegafur and its active metabolite, 5-FU, were simultaneously observed. Also pharmacokinetic parameters were compared with each others. On the other hand, most previous studies of lymphatic transport have not addressed the question of whether an increase in mesenteric or thoracic lymph transport by the manipulation of a suspected variable was due to a selective delivery to the intestinal lymphatics or an overall increase availability. Therefore, based on a physiologically based pharmacokinetic model which represents the characteristics of lymphatic systems, we are also going to determine the contributions of mesenteric lymph transport versus thoracic lymph transport of tegafur reported in reference(13). In comparison with tegafur solution, AUC and mean residence time of plasma tegafur were significantly increased in W/O emulsion but significantly decreased in O/W emulsion. Lymph flow rates were similar in both solution and W/O emulsion but half in O/W emulsion. AUC of tegafur in mesenteric lymph and in plasma for W/O emulsion were 3.7 times and 2.9 times more than those for O/W emulsion, respectively. And AUC of 5-FU in thoracic lymph for W/O emulsion was 3.7 times more than that for O/W emulsion. These results suggested that lymphatic delivery or tegafur by W/O emulsion was more effective than that by on emulsion due to its differences or formation ability of chylomicrons.

• The Korean Journal of Pain
• /
• v.11 no.1
• /
• pp.54-59
• /
• 1998

Background: Tramadol administered epidurally is known to have one-thirtieth the potency of morphine for treatment of pain following abdominal surgery. We designed a prospective, randomized, controlled study to evaluate the analgesic efficacy and safety of combined epidural infusion of bupivacaine and tramadol with 2-day infusor as ompared to bupivacaine and morphine combined epidural infusion. Methods: Sixty healthy women scheduled for Cesarean delivery were assigned randomly in double- blind fashion: Group 1 (n=20) were given a mixture of morphine 10 mg(1 ml), 0.5% bupivacaine 40 ml and normal saline(NS) 40 ml; Group 2(n=20) a mixture of tramadol 300 mg(6 ml), 0.5% bupivacaine 40 ml and NS 54 ml; Group 3(n=20) or a mixture of tramadol 500 mg(10 ml), 0.5% bupivacaine 50 ml and NS 50 ml, of continuous dose via epidural route following 1% lidocaine 6 ml as bolus dose for 48 hours postoperatively. We evaluated the analgesic efficacy and side effects of these three groups using visual analogue pain scale (VAPS) and verbal rating scale (VRS). Results: VAPS of group 1 and 3 were lower than group 2, and VAPS of group 1 was lower than group 3(12, 24, 36, 48 hours). VRS of group 1 and 3 were lower than group 2 (12, 24, 36 hours). There were incidences of pruritus was 16 patients in group 1. Conclusions: Tramadol does possess the analgesia effect of morphine, but has the added analgesia following increment. Further research to determine the most effective administration method and reguired dosage of tramadol is further needed.

• The Journal of Korean Society for School & Community Health Education
• /
• v.14 no.2
• /
• pp.47-57
• /
• 2013

Backgrounds: According to a high interest in health these days, a bicycle is being highlighted as a means of leisure activity and auxiliary transportation means. Along with an increase in this interest, there is tendency that even the width of bicycle utilization gets diverse and that bicycle accident is also rapidly growing. Purpose: The purpose of this study was to suggest a prevention measure available for reducing occurrence of bicycle accidents by analyzing the Epidemiological characteristics according to age and injury severity in bicycle-injured patients. Methods: This study analyzed 115 materials suitable for this study by examining a medical record of patients, who received the hospitalized treatment owing to bicycle accident from January 1, 2011 to December 31 at one general hospital in S city. Results: The male-and-female ratio of bicycle-injured patients stood at about 7:3. The average age was 38.14(${\pm}21.59$) years old. The largest injury happened in 40-59 years old(31.3%). The averagely hospitalized period was 17.33(${\pm}18.12$) days. Injury severity was the ratio of 2:8 in a mild case versus a serious case. As for drinking and smoking characteristics according to age, the injury occurred the most in between 40 and 59 years old for people with drinking and smoking and in under 19 years for people without drinking and smoking. According to injury severity, the ratio of serious case got higher in the higher age. This was indicated(${\chi}^2$=15.675, p=0.001) to be statistically significant. Conclusion: In this study, a bicycle accident was indicated to have high injury risk in young children, adolescents, and old-age group. Prevention measure and publicity are demanded for reducing injury occurrence such as the prevention education for bicycle accident and wearing protective gear focusing on the ages of corresponding to groups with risk of injury occurrence. In addition, the security of safe movement route is necessarily demanded in order to increase application level as an auxiliary transportation means.