• Journal of Convergence Korean Medicine
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• v.6 no.1
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• pp.5-20
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• 2024

Objectives: This study was aimed to evaluate the hemodynamic feasibility using pulse parameters as a way to establish safe dose guidelines for Chunwangbosim-dan, and to provide a foundation for developing evidence-based guidelines for clinical use. Methods: Forty-one volunteers were recruited to participate in a study examining the changes in pulse wave characteristics following the ingestion of Chunwangbosim-dan, over a period of 2 weeks, and pulse wave measurements were taken before and after the administration. Pulse wave parameters were measured in this study using a 3-dimensional radial pulse tonometry device(DMP-Lifeplus). In addition, questionnaire, blood pressure, temperature, and body composition were also measured as secondary measures. Results: Fifteen minutes after administration of Chunwangbosim-dan, the non-adverse event group(non-AE) exhibited a statistically significant increase in several power and pressure-related parameters, including h1, h3, h4, h5, SA, PA and PW, while the adverse event group(AE) showed a trend of decreasing stroke volume and increasing Systemic Vascular Resistance Index(SVRI) and applied pressure. After 2 weeks of administration, non-adverse event group(non-AE) exhibited significant changes in standard deviation of pulse rate and HRV_LH ratio. Notably, there are significant differences between AE group and non-AE group in h4/h1, w/t, applied pressure, SV and pulse rate. Conclusion: These findings suggest that pulse parameters may be a useful way to establish safe dosing guidelines for Chunwangbosim-dan. Further research is needed to confirm these results and to develop evidence-based guidelines for clinical use.

• The Korean Journal of Pain
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• v.37 no.2
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• pp.119-131
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• 2024

There are growing concerns regarding the safety of long-term treatment with opioids of patients with chronic non-cancer pain. In 2017, the Korean Pain Society (KPS) developed guidelines for opioid prescriptions for chronic non-cancer pain to guide physicians to prescribe opioids effectively and safely. Since then, investigations have provided updated data regarding opioid therapy for chronic non-cancer pain and have focused on initial dosing schedules, reassessment follow-ups, recommended dosage thresholds considering the risk-benefit ratio, dose-reducing schedules for tapering and discontinuation, adverse effects, and inadvertent problems resulting from inappropriate application of the previous guidelines. Herein, we have updated the previous KPS guidelines based on a comprehensive literature review and consensus development following discussions among experts affiliated with the Committee on Hospice and Palliative Care in the KPS. These guidelines may assist physicians in prescribing opioids for chronic non-cancer pain in adult outpatient settings, but should not to be regarded as an inflexible standard. Clinical judgements by the attending physician and patient-centered decisions should always be prioritized.

• Tuberculosis and Respiratory Diseases
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• v.40 no.5
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• pp.474-482
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• 1993

Background: As a physiologic plasminogen activator, tissue-type plasminogen activator (t-PA) could induce effective thrombolysis in massive pulmonary embolism, without the risk of systemic hemorrhage. However, therapeutic doses of t-PA has been associated with systemic lytic state, and fibrin selectivity may be influenced by the dosing regimen of t-PA. To investigate the effects of duration of t-PA infusion on blood coagulation system, we performed this study. Method: In a canine model of pulmonary embolism, which was induced by injection of autologous blood clots, we administered equal doses of t-PA (1 mg/kg) over 15 minutes in $t-PA_{15}$ group, over 180 minutes in $t-PA_{180}$ group, and only saline in control group. Then serial blood samplings were made to check complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, fibrin, plasminogen, ${\alpha}_2$-antiplasmin, coagulation factor V and VIII, and fibrin(ogen) degradation products. Results: 1) In all 3 groups, complete blood count showed same changes. Hemoglobin, hematocrit and platelet count decreased, but WBC count increased. 2) Prothrombin time, activated partial thromboplastin time, and thrombin time were prolonged during 15-60 minutes after t-PA administration in $t-PA_{15}$ group, and from 30 minutes through 180 minutes after administration in $t-PA_{180}$ gorup. 3) Fibrin, ${\alpha}_2$-antiplasmin, and cogulation factor V and VIII decreased in both $t-PA_{15}$ and $t-PA_{180}$ group, but returned to basal levels earlier in $t-PA_{15}$ group. 4) Fibrin(ogen) degradation products increased after pulmonary embolism in all groups, and further increased in both $t-PA_{15}$ and $t-PA_{180}$ groups after t-PA infusion. But more pronounced increment was noted in $t-PA_{180}$ gorup. Conclusion: In pulmonary embolism, the shorter (15 minutes) infusion of t-PA would have less risk of systemic hemorrhage than the longer (180 minutes) infusion when the doses is equal. And, this suggests that manipulating the duration of t-PA infusion can reduce the risk of major bleeding.

• Tuberculosis and Respiratory Diseases
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• v.50 no.3
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• pp.293-299
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• 2001

Background : Sustained-release theophylline, which is generally prescribed as a twice-daily equal-dose regimen, is one of the more common asthma treatments. The development of a sustained-release drug delivery technology that enables improved control of the theophylline blood levels represents a significant advancement in both the efficacy and safety of dosing. Method : A crossover study was conducted with 25 adult chronic asthmatic patients requiring daily bronchodilator therapy. The study group included thirteen males and twelve females with ages ranging from 19 to 71 years. The overall approach was to place the patients first on the twice-daily preparation($Etheophyl^{(R)}$) for 28 days at 8 AM and 8 PM, and measure the pulmonary function and theophylline level on the 28th day. The patients were subsequently switched to the once-daily preparation($Uniphyl^{(R)}$) in the same daily dose at 8 PM on the 29th day and the same parameters were measured on the 56th day. Results : The mean serum levels of theophylline were $8.18{\pm}1.66\;{\mu}g/ml$ in the $Etheophyl^{(R)}$-treated period and $8.00{\pm}1.75\;{\mu}g/ml$ in the $Uniphyl^{(R)}$-treated period. ln addition, the $FEV_1$ showed $71.40{\pm}7.48$ percent in the $Etheophyl^{(R)}$-treated and $69.18{\pm}9.00$ percent in the $Uniphyl^{(R)}$-treated period. Thus there were no significant differences between the once-daily and twice-daily preparation. Conclusion : The results indicated little clinical differences between the two medications. The two drugs are equally effective in controlling asthma over the four weeks of treatment.

• Korean Journal of Veterinary Research
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• v.40 no.2
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• pp.361-371
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• 2000

It has been recently reported that 2-bromopropane (2-BP) induces male reproductive toxicity in both human and experimental animals. However, delayed effects of 2-BP on male reproductive system have not been investigated in detail. The present study was conducted to investigate the testicular toxicity of 2-BP and to determine the recovery of normal spermatogenesis in Sprague-Dawley rats. Male rats aged 5 weeks were administered 1,000mg/kg 2-BP by gavage daily for 4 weeks and sacrificed sequentially at 1, 2, 3, 4 and 12 weeks after initiation of 2-BP treatment. Testicular toxicity was evaluated qualitatively by histopathological examinations and quantitatively by reproductive organ weights, spermatid head count, and repopulation index. In the 2-BP treated rats, the body weights was significantly suppressed and the weights of testes and epididymides were also decreased in a time-dependent manner. On histopathological examination, spermatogonia in stages I-VI and preleptotene and leptotene spermatocytes in stages VII-IX were strongly depleted at 1 week of dosing. Spermatogonia were depleted extensively in all spermatogenic stages at 2 weeks. Continuing with the evolution of spermatogenic cycle, zygotene spermatocytes, pachytene spermatocytes, and round spermatids were sequentially depleted at 2, 3, and 4 weeks of dosing due to the depletion of their precursor cells. Vacuolization of Sertoli cells and spermatid retention were also observed at all time points, suggesting that 2-BP induced Sertoli cell dysfunction. At 12 weeks, after 8 weeks recovery, most of the tubules appeared severely atrophic and were lined by Sertoli cells only. Leydig cell hyperplasia in the interstitial tissue was also found. In addition, dramatic reductions in the number of spermatid heads and repopulation index were observed, indicating that 2-BP-induced testicular injury is irreversible. These results indicate that 4 weeks repeated-dose of 1,000mg/kg 2-BP results in a progressive germ cell loss due to the depletion of spermatogonia followed by long-term testicular atrophy in SD rats.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.123-134
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• 1993

Background: Tissue-type plasminogen activator is a physiologic activator, which has high affinity for fibrin and is activated by fibrin. Because of these properties, t-PA has the potential to induce effective thrombolysis without producing a systemic lytic state. In practice, however, therapeutically efficacious doses of t-PA has been associated with the development of a systemic lytic state. As experience with t-PA has accumulated, it has suggested that the fibrin selectivity is influenced by the dose and duration of t-PA infusion, and many studies have performed in an attempt to optimize the duration of t-PA regimen. Methods: This study was designed to assess the thrombolytic efficacy of t-PA and the differences of two dosing regimens of t-PA (infusion of 1 mg/kg t-PA over 15 or 180 minutes) in a canine model of pulmonary embolism, induced by injection of radioactive autologous blood clots. By continuously counting over both lung fields with a external gamma counter, we correlated rate and extent of pulmonary thrombolysis with corresponding pulmonary hemodynamics in addition to the gas analyses of arterial and mixed venous blood. Results: 1) While total clot lysis was similar ($36.2{\pm}3.3%$ and $39.6{\pm}2.3%$ respectively, p>0.05) when t-PA was infused over 15 or 180 minutes, the rate of lysis during infusion was markedly increased with the shorter infusion ($81.4{\pm}16.8%/hr$ vs $37.3{\pm}2.4%/hr$, p<0.05). 2) The duration of thrombolysis was $63.3{\pm}22.2$ minutes although t-PA was administered over 15 minutes, and it was only $148.5{\pm}14.0$ minutes in case of the infusion over 180 minutes (p<0.05). 3) The increased rate of thrombolysis with the shorter infusion was accompanied by a faster amelioration of cardiopulmonary impairment from pulmonary embolism (p<0.05). Conclusion: It is concluded that the shorter (15 minutes) infusion of t-PA is superior to the longer (180 minutes) infusion when the dose is equal, in consideration of the faster improvement in cardiopulmonary impairment from pulmonary embolism.

• Korean Chemical Engineering Research
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• v.52 no.5
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• pp.581-586
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• 2014

Main objects for wastewater treatment operation are to maintain effluent water quality and minimize operation cost. However, the optimal operation is difficult because of the change of influent flow rate and concentrations, the nonlinear dynamics of microbiology growth rate and other environmental factors. Therefore, many wastewater treatment plants are operated for much more redundant oxygen or chemical dosing than the necessary. In this study, the optimal control scheme for dissolved oxygen (DO) is suggested to prevent over-aeration and the reduction of the electric cost in plant operation while maintaining the dissolved oxygen (DO) concentration for the metabolism of microorganisms in oxic reactor. The oxygen uptake rate (OUR) is real-time measured for the identification of influent characterization and the identification of microorganisms' oxygen requirement in oxic reactor. Optimal DO set-point needed for the micro-organism is suggested based on real-time measurement of oxygen uptake of micro-organism and the control of air blower. Therefore, both stable effluent quality and minimization of electric cost are satisfied with a suggested optimal set-point decision system by providing the necessary oxygen supply requirement to the micro-organisms coping with the variations of influent loading.

• Korean Journal of Clinical Pharmacy
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• v.18 no.2
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• pp.114-119
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• 2008

Alendronate is a bisphosphonate that selectively inhibits osteoclast-mediated bone resorption. Dosing convenience is an important element for the enhancement of patient compliance and the effective management of osteoporosis. The purpose of this study was to compare the effectiveness and compliance among alendronate pharmaceutical products (oral once-weekly alendronate 70 mg, daily alendronate 10 mg, and once-weekly alendronate 70 mg with Vitamin $D_3$ 2800 IU) in terms of the change in bone mineral density (BMD), biochemical markers, and compliance estimates. A retrospective chart review was conducted in patients with osteoporosis who received alendronate 70 mg (Group 1), alendronate 10 mg (Group 2), or alendronate 70 mg with Vitamin D3 2800 IU (Group 3) at the endocrinology department of a hospital in Korea from Jan. 1, 1998 to Mar. 31, 2008. The primary endpoints were the increases in spine antero-posterior BMD T-score and femur trochanter BMD T-score, and the compliance of alendronate products. Secondary endpoints included changes in bone turnover-related biochemical markers including bone-specific alkaline phosphatase, urinary N-terminal telopeptides (NTX) and osteocalcin, and in serum vitamin $D_3$ concentration. There was no statistical difference in the BMD increase among the three alendronate products; spine BMD T-score increased by $0.49{\pm}0.52$, $0.39{\pm}0.48$ and $0.50{\pm}0.41$, and femur trochanter BMD T-score by $0.29{\pm}0.42$, $0.21{\pm}0.53$ and $0.24{\pm}0.22$ in Group 1, 2 and 3, respectively. With respect to the increases in femur trochanter BMD T-score and the decreases in NTX and osteocalcin, 70 mg once-weekly group was remarkably superior to 10 mg daily group (p < 0.05) The compliance of 70 mg once-weekly group was significantly higher than that of 10 mg daily treatment group (p < 0.001). In conclusion, all three alendronate treatment groups were equivalent in effectiveness, and the compliance of 70 mg once-weekly group was better than that of 10 mg daily treatment group.

• Korean Journal of Veterinary Research
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• v.51 no.4
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• pp.253-257
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• 2011

Amikacin is a semisynthetic derivative of kanamycin and primarily active against aerobic Gram-negative-pathogens with limited activity against Gram-positive bacteria. Meager study was reported on pharmacokinetic data on multi-days administration of amikacin. Hence, pharmacokinetics study was done in five clinically healthy goats (n = 5), after intravenous bolus injection of amikacin sulfate at the dose rate of 10 mg/kg body weight daily for three consecutive days. The amikacin concentrations in plasma and pharmacokinetics-parameters were analyzed by using microbiological assay technique and noncompartmental open-model, respectively. The mean peak plasma concentrations (Mean ${\pm}$ SD) of amikacin at time zero ($Cp^{0}$) was $114.19{\pm}20.78$ and $128.67{\pm}14.37{\mu}g/mL$, on day 1st and 3rd, respectively. The mean elimination half-life ($t_{1/2}ke$) was $1.00{\pm}0.28h$ on day 1st and $1.22{\pm}0.29h$ on day 3rd. Mean of area under concentration-time curve ($AUC_{0{\rightarrow}{\infty}}$) was $158.26{\pm}60.10$ and $159.70{\pm}22.74{\mu}g.h/mL$, on day 1st and 3rd respectively. The total body clearance ($Cl_{B}$) and volume of distribution at steady state (Vdss) on day 1st and 3rd were $Cl_{B}=0.07{\pm}0.02$ and $0.06{\pm}0.01L/h.kg$ and $Vdss=0.10{\pm}0.03$ and $0.11{\pm}0.05L/kg$, respectively. No-significant difference was noted in both drug-plasma concentration and pharmacokinetics-parameters, respectively. Amikacin concentration in plasma was found higher up-to 4 h and 6 h onward on down-ward trends favour to reduce toxicity. Which also support the pharmacokinetic-pharmacodynamic way of dosing of aminoglycosides and hence, amikacin may be administered 10 mg/kg intravenously daily to treat principally Gram-negative pathogens and limitedly Gram-positive-pathogens.

• Journal of Veterinary Clinics
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• v.10 no.2
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• pp.147-155
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• 1993

This study was carried out to investigate the Preventive and treatment effects of mixed compound of vitamin E and selenium, and ursodeoxycholic acid on the pre-parturient and post-parturient fatty liver of high. yielding dairy cows. Thirty pregnant dairy cows(2 weeks preparturition) were divided into clinical(13cows) and subclinical(17 cows) groups based upon blood chemical values, blood serum protein levels and clinical symptoms. The clinical group was subdivided into treated clinical group(6 cows) and non-treated clinical group(7 cows). The cows(treated clinical group) with fatty liver diagnosed before parturition were dosed with mixed compound of vitamin I(1head) and selenium(10mg/head) intramuscularly once before and after parturition, respectively. These cows(treated clinical group) were also given ursodeoxycholic acid(50g/head) intramuscularly 3 times before parturition. The cows(treated clinical group) with fatty liver diagnosed after parturition were also given the same compounds as dosed to the above cows at same dose rate once or 3 times, respectively after parturition. Blood samples were collected from the cows on 4th, 7th and 2nd day of preparturition and on 1st, 7th, 14th and 20th day of postparturition. Blood chemical values(non-esterified fatty acid : NEFA) concentration, serum aspartate aminotransferase activity, serum ${\gamma}$-glutamyl transpeptidase activity, bilirubin concentration, glucose level) were checked and clinical symptoms of the cows were also observed. 1. The cows in non-treated clinical group showed severe depression, anorexia and diarrhea from prepartum period, and retained palcenta, endometritis, ketosis, abomasal displacement and mastitis after parturition. Cows in treated clinical group showed moderate depression, anorexia, diarrhea during preparturient period, but they were relieved within a week from parturition. Cows in subclinical group showed mild depression, anorexia and diarrhea after parturition, but these symptoms were not observed in prepartum period. 2. NEFA concentration, serum aspartate aminotransferase activity, serum ${\gamma}$-glutamyl transpeptidase activity and bilirubin concentration observed In the cows of treated clinical group were significantly lower than those of the cows non-treated clinical group. The blood glucose concentration of the cows in treated clinical group were higher than those of the cows in non-treated clinical group. These results indicate that the preparturient and postparturient fatty liver of high-yielding dairy cows could be reduced by dosing the animals with appropriate amounts of mixed compound of vitamin I and selenium, and ursodeoxycholic acid at proper times of the preparturition and postparturition of the dairy cows.