7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.
Pancoast tumor was specific lung carcinoma that has been symptoms and signs according to locations. It was located in peripheral,and involved the extrathoracic structures more than parenchyme of the lung. At 1838, Hare reported it, and at 1932 Pancoast was first described it. Prior to 1950,superior sulcus tumor was considered uniformly fatal, but at 1961 Paulson and Shaw advocated the use of preoperative irradiation therapy and followed by an extended en bloc resection. Recently we were experienced 2 cases of pancoast tumor managed with same method. One was 60-years old man that has been recommended preoperative radiation therapy with dose of 3000 cGy to 20 fractions and followed resection after 4 weeks, the other was 53-years old man that has been recommended a dose of 4000 cGy to 20 fractions and followed resection after 4 weeks. On tumor histology first case was large cell carcinoma and second case was squamous cell carcinoma. all patients was complicated atelectasis. First patient was expired with brain metastasis after 17 months, second was expired after 6 months.
Background: On June 18, 2017, Korea's first commercial nuclear reactor, the Kori Nuclear Power Plant No. 1, was permanently suspended, and the capacity of nuclear power generation facilities will be adjusted according to the governments denuclearization policy. In these circumstances, it is necessary to assess the quality of radiation safety management in nuclear power plants in Korea by evaluating the radiation dose associated with them. Materials and Methods: The average annual radiation dose per unit, the annual radiation dose per person, and the annual dose distribution were analyzed using the radiation dose database of nuclear reactors for the last 5 years. The results of our analysis were compared to the specifications of the Nuclear Safety Act and Medical Law in Korea. Results and Discussion: The annual average per unit radiation dose of global major nuclear power generation was 720 man-mSv, while that of Korea's nuclear power plants was 374 manmSv. No workers exceeded 50 mSv per year or 100 mSv in 5 years. The individual radiation dose according to occupational exposure was 0.59 mSv for nuclear workers, 1.77 mSv for non-destructive workers, and 0.8 mSv for diagnostic radiologists. Conclusion: The radiation safety management of nuclear power plants in Korea has achieved the best outcomes worldwide, which is considered to be the result of the as-low-as-reasonably-achievable (ALARA) approach and strict radiation safety management. Moreover, the occupational exposures were also very low.
Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. EPA and OECD are developing screening programs using validated test systems to determine whether certain substances may have an effect on humans. In the present study, the establishment of in vivo short-term test system for pubertal female assay with thyroid to detect endocrine disrupting chemicals was tried using a model substance, methoxychlor (MC), a chlorinated hydrocarbon insencticide. Forty female rats were assigned to four groups. MC was administered at dose levels of 0, 8, 40 and 200mg/kg by gavage to female rats from day 21 post partum to the completion of vaginal opening. We evaluated body weight change, age at vaginal opening, onset of estrous cyclicity, age at first esturs, ovary weight, and serum concentrations of thyroxine and thyroid stimulating hormone in female rats. The age at vaginal opening of females receiving 40 200mg/kg was significantly younger than control. The onset of estrus cyclicity and age at first estrus of females receiving 200mg/kg was also younger than controls. There was no effect of treatment on body weight, ovary weight, and hormone concentration. Based on these results, it can be concluded that application of MC at dose level of 40mg/kg affects the vaginal opening and application of MC at dose level of 200mg/kg accelerates the vaginal opening and the onset of estrus cylicity.
Proceedings of the Korean Society of Applied Pharmacology
/
2003.11a
/
pp.108-108
/
2003
The current study was performed to observe the effects of Panax ginseng (PG) and P. quinquefolia (PQ) on hemodynamics such as blood flow rate (BF), blood flow velocity (BV), heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP, and body temperature (BT) in healthy young men. After testing equality of variance, Student's t-test using PROC TTEST was examined to. prove statistical differences between control and ginseng conditions at each time point. It was found that the BF data were fluctuated by personal deviation. In order to minimize the deviation, the results obtained for 6 hrs were reconstituted after dividing them into two periods of the first half from 1 to 3 hrs and of the latter half from 3.5 to 6 hrs. And then the reconstitution data and dose-response curves were obtained. Blood flow such as BF and BV shows significant increases both two periods in the dose of PG 2.25 and PG 9.0, whereas significant decrease in the dose of PG 4.5. However, in the PQ groups, the middle dose PQ 4.5 shows the highest significant increase among the three doses. Except for PG 2.25 in HR, other doses show significant decreases both in the first half and latter half. SBP of PQ 9.0 shows only a significant decrease in the first half; on the other hand, in the latter half, PG 4.5, PG 9.0 and PQ 9.0 significantly increase SBP. In addition, DBP of PG 2.25 and PG 4.5 show significant increase in the both periods. In the BT, PQ groups show gradual decrease from PQ 2.25 to PQ 9.0; however, PG groups show differently. PG 4.5 shows significant decrease, but PG 9.0 shows a increase without statistical meanings. In summary, PG is more effective in respect to keeping homeostasis of hemodynamics.
Kim, Tae-Hwan;Baik, Ji Sue;Heo, Kyu;Kim, Joong Sun;Lee, Ki Ja;Rhee, Man Hee;Kim, Sung Dae
Journal of Radiation Protection and Research
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v.40
no.3
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pp.187-193
/
2015
Deleterious effects of high dose radiation exposure with high-dose-rate are unarguable, but they are still controversial in low-dose-rate. The regulator of G-protein signaling (RGS) is a negative regulator of G protein-coupled receptor (GPCR) signaling. In addition, it is reported that irradiation stress led to GPCR-mediated mitogen-activated protein kinase (MAPK) and phosphotidylinositol 3-kinase (PI3-k) signaling. The RGS mRNA expression profiles by whole body radiation with low-dose-rate has not yet been explored. In the present study, we, therefore, examined which RGS was modulated by the whole body radiation with low-dose-rate ($3.49mGy{\cdot}h^{-1}$). Among 16 RGS expression tested, RGS6, RGS13 and RGS16 mRNA were down-regulated by low-dose-rate irradiation. This is the first report that whole body radiation with low-dose-rate can modulate the different RGS expression levels. These results are expected to reveal the potential target and/or the biomarker proteins associated with male testis toxicity induced by low-dose-rate irradiation, which might contribute to understanding the mechanism beyond the testis toxicity.
Kim, Rin-Ah;Dho, Ho-Seog;Kim, Tae-Man;Cho, Chun-Hyung
Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
/
v.18
no.2_spc
/
pp.317-325
/
2020
The Korea Radioactive Waste Agency plans to expand the storage capacity of radioactive waste by constructing a radioactive waste inspecting building to solve the problem of the lack of inspection space and drum-handling space in the radioactive waste receipt and storage building for the first-stage disposal facility. In this study, the exposure doses of radiation workers that handle new disposal containers for decommissioning waste in the storage areas of the radioactive waste inspecting building were calculated using the Monte Carlo N-particle transport code. The annual collective dose was calculated as a total of 84.8 man-mSv for 304 new disposal containers and an estimated annual 306 working hours for the radiation work. When the 304 new disposal containers (small/medium type) were stored in the storage areas, it was found that 25 radiation workers should be involved in acceptance/disposal inspection, and the estimated exposure dose per worker was calculated as an average annual value of 3.39 mSv. When the radiation workers handle the small containers in high-radiation dose areas, the small containers should be shielded further by increasing the concrete liner thickness to improve the work efficiency and radiation safety of the radiation workers. The results of this study will be useful in establishing the optimal radiation working conditions for radiation workers using the source term and characteristics of decommissioning waste based on actual measurements.
Background: Exercise is one of the most common precipitants of acute asthma encountered in clinical practice. The development of airflow limitation that occurs several minutes after vigorous exercise, i. g. exercise-induced bronchoconstriction(EIB), has been shown to be closely correlated with the nonspecific bronchial hyperresponsiveness, which is the hallmark of bronchial asthma. All previous reports that assessed the correlation of EIB to nonspecific bronchial hyperresponsiveness have focused on airway sensitivity($PC_{20}$) to inhaled bronchoconstrictor such as methacholine or histamine. However, maximal airway narrowing(MAN), reflecting the extent to which the airways can narrow, when being exposed to high dose of inhaled stimuli, has not been studied in relation to the degree of EIB. Methods: Fifty-six children with mild asthma(41 boys and 15 girls), aged 6 to 15 years(mean${\pm}$SD, $9.9{\pm}2.5$ years) completed this study. Subjects attended the laboratory on two consecutive days. Each subject performed the high-dose methacholine inhalation test at 4 p.m. on the first day. The dose-response curves were characterized by their position($PC_{20}$) and MAN, which was defined as maximal response plateau(MRP: when two or three data points of the highest concentrations fell within a 5% response range) or the last of the data points(when a plateau could not be measured). On the next day, exercise challenge, free running outdoors for ten minutes, was performed at 9 a.m.. $FEV_1$ was measured at graduated intervals, 3 to 10 minutes apart, until 60 minutes after exercise. Response(the maximal ${\triangle}FEV_1$ from the pre-exercise value) was classified arbitrarily into three groups; no response((-) EIB: ${\triangle}FEV_1$<10%), equivocal response ($({\pm})$EIB:10%<${\triangle}FEV_1$<20%) and definite response($({\pm})$EIB:${\triangle}FEV_1$>20%). Results: 1) When geometric mean $PC_{20}$ of the three groups were compared, $PC_{20}$ of (+) EIB group was significantly lower than that of (-)EIB group. 2) There was a close correlation between $PC_{20}$ and the severity of EIB in the whole group(r=-0.568, p<0.01). 3) Of the total 56 subjects, MRP could be measured in 36 subjects, and the MRP of these subjects correlated fairly with the severity of EIB(r=0.355, p<0.05) 4) The MAN of (+) EIB group was significantly higher than that of (-)EIB group(p<0.01). 5) The MAN correlated well with the severity of EIB in the whole group(r=0.546, p<0.01). Conclusion: The degree of MAN as well as bronchial sensitivity($PC_{20}$) to methacholine is correlated well with the severity of EIB. The results suggest that the two main components of airway hyperresponsiveness may be equally important determinants of exercise reactivity, although the mechanism may be different from each other. The present study also provides further evidence that EIB is a manifestation of the increased airway reactivity characteristic of bronchial asthma.
There had been few reports of arachnoid cyst accompanying psychiatric disturbance and no report treated with low-dose risperidone administration. We report a patient, developed first-transient psychotic episode considered to be provoked by an arachnoid cyst, responsive to risperidone, which was found in the middle cranial fossa as follows. A 57-year-old man was admitted by suddenly developed headache, auditory hallucination, delusion of persecution and, an arachnoid cyst in the anteromedial aspect of middle cranial fossa was found on MRI after admission. The psychotic episode was first to him and he was also negative to other clinical evaluation including endocrine abnormality, his psychotic symtom was suspected to be induced by arachnoid cyst and was well controlled to low-dose risperidone administration. He left hospital free from psychotic symptoms on 14 hospital days.
Kim, Il-Man;Son, Eun Ik;Kim, Dong Won;Yim, Man Bin
Journal of Korean Neurosurgical Society
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v.29
no.6
/
pp.738-743
/
2000
Objectives : The less invasive stereotactic surgery of hypertensive intracerebral hematoma has been preferred. Many techniques were developed to facilitate aspiration of a dense blood clot in acute stage. Authors describe a method for evacuation of putaminal hematoma via computerized tomography(CT)-aided free-hand stereotactic infusion of urokinase and frequent negative pressure aspiration. Patients and Methods : A total of ten patients with spontaneous putaminal hematoma underwent surgery with negative pressure aspiration in the three-year period. All procedures were performed within 12 hours of insult. A silicone ventricular catheter was inserted into the center of hematoma through a burr hole at the Kocher's point under local anesthesia. In a typical case of putaminal hematoma, the trajectory of catheter was pointed the center of hematoma parallel to sagittal plane vertically and the external auditory meatus posteriorly. Immediately after the first trial of hematoma aspiration low-dose urokinase solution(2,000IU/5ml saline) was administrated through the catheter and drain was clipped for 30 minutes. Subsequently, the partially liquified hematoma was manually aspirated using a 10ml syringe with a negative pressure of less than 2 to 3ml. The procedure was carefully repeated every 1 hour until the hematoma was near totally evacuated. Results : The patients population consisted composed of 4 men and 6 women with a mean age of 61.6 years. All had major neurological deficits preoperatively. The mean hematoma volume was 44.3 ml and hematoma was drained for 20 to 48 hours. No complications such as rebleeding, meningitis, or malplaced catheter were noted. Outcome was moderately disabled in four patients and good recovery in three patients. Conclusion : Although the frequent negative pressure aspiration and low-dose urokinase infusion has the disadvantage of possbility of rebleeding and infection, it is consisdered to be an effective method because it allows a simple, safe, and complete removal of hematoma.
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