• The Korean Journal of Pharmacology
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• v.16 no.2 s.27
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• pp.55-70
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• 1980

The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.

• Journal of Food Hygiene and Safety
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• v.21 no.2
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• pp.118-128
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• 2006

This study was conducted to determination of the endocrine distruptor function of 'Parabens' by dosing ethyl paraben, propyl paraben, isopropyl paraben, butyl paraben and isobutyl paraben to the immature SD rats. 18 groups were given vehicle control group, negative control group (Dibutyl phthalate), postive control group ($1'7-{\alpha}$ Ethynylestrdiol) and each paraben groups involved 3 dose level. Rats were injected with 62.5, 250 and 1,000mg/kg from postnatal day 19 till 21 once a day in subcutaneous and a total 3, times. There was no treatment related death. but, subcutaneous nodule, edema, alopecia and scrub formation on injection site was observed. These signs was become worse in high dose level. these signs was cause from physical stimulation by test substance which parabens were mix with com oil as vehicle. In the analysis of organ weights, absolute and relative weights of brain, spleen, liver, thymus, heart, kidneys, adrenals, ovaries and vagina were no difference with control group. but, wet and blotted weight of uterus was increased in every high dose parabens treat group. Especially, all dose level of isobutyl paraben was showed increment of uterus weight. uterus dilatation of parabens treated group was observed in gross anatomic pathology and these result was agree with wet and blotted weight of uterus. In the result of this study, estrogenic effect as endocrine distruptor was observed in ethyl paraben, propyl paraben, isopropyl paraben, butyl paraben and isobutyl paraben. and it was considered isobutyl paraben has highest estrogrnic effect under the condition of this study.

• Pediatric Infection and Vaccine
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• v.23 no.2
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• pp.109-116
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• 2016

Purpose: Recent observational studies have found that vitamin D deficiency is associated with respiratory tract infections. However, randomized controlled trials (RCTs) regarding the efficacy of vitamin D in childhood respiratory tract infection (RTI) have yield inconsistent results. We performed a systematic review and meta-analysis to evaluate the association between vitamin D supplementation and the risk of RTI. Methods: A comprehensive search was conducted using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trial. Randomized controlled trials of vitamin D supplementation for prevention of RTI in children were included for the analysis. Cochrane Collaboration's tool for assessing the risk of bias was used to assess the quality of the studies. Pooled risk ratios with 95% confidence intervals (CIs) were meta-analyzed using Review Manager 5.3. Results: A total of seven RCTs were included in the meta-analysis. According to a random-effects model, the risk ratio for vitamin D supplementation was 0.82 (95% CI: 0.69-0.98) and $I^2=62%$ for heterogeneity. On subgroup analysis, heterogeneity decreased in the subgroup with follow-up less than 1 year, participants ${\geq}5years$ of age, patients subgroup, and subgroup with dosing daily. Funnel plot showed that there might be publication bias in the field. Conclusions: The present meta-analysis supports a beneficial effect of vitamin D supplementation for the prevention of RTI in children. However, the result should be interpreted with caution due to limitations including a small number of available RCTs, heterogeneity among the studies, and potential publication bias.

• Clinical and Experimental Pediatrics
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• v.51 no.6
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• pp.584-596
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• 2008

Purpose : This study was conducted to investigate treatment compliance and related factors in pediatric patients. Methods : Three hundred and fifty-five patients diagnosed with various acute diseases at a teaching hospital or clinic in October 2003 were enrolled. Data were analyzed using the Health Belief Model, which includes items on self-efficacy and family assistance. Results : The study found that 62.9% of pediatric patients adhered faithfully to agreed-upon hospital revisits, 41.6% complied with dose timings instructions, 65.8% precisely took medication, and 27.2% complied with all of these requirements. According to ${\chi}^2$ test analysis, the factors found to be related to therapeutic compliance (the taking of medicines requested) were; susceptibility, severity, benefit, barriers, mother's self-efficacy, and family assistance (P<.05). Multiple logistic analysis and path analysis showed that susceptibility, severity, barriers, and mother's self-efficacy were related to therapeutic compliance (P<.05). Moreover, mother's self-efficacy was identified as the most important factor. Conclusion : To improve therapeutic compliance among pediatric patients, parental education is necessary, and a health care professional must take a thorough history of how the medication was taken before it is assumed that treatment failure is attributable to the medication prescribed. Furthermore, the type of device recommended for dosing should be determined by clinicians. In addition, it is important that pediatric medications be discussed in relation to their palatability and internal acceptability.

• Journal of Chest Surgery
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• v.37 no.6
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• pp.504-510
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• 2004

Background: Vasodilatory shock after cardiac surgery may result from the vasopressin deficiency following cardio-pulmonary bypass and sepsis, which did not respond to usual intravenous inotropes. In contrast to the adult patients, the effectiveness of vasopressin for vasodilatory shock in children has not been known well and so we reviewed our experience of vasopressin therapy in the small babies with a cardiac disease. Material and Method: Between February and August 2003, intravenous vasopressin was administrated in 6 patients for vasodilatory shock despite being supported on intravenous inotropes after cardiac surgery. Median age at operation was 25 days old (ranges; 2∼41 days) and median body weight was 2,870 grams (ranges; 900∼3,530 grams). Preoperative diag-noses were complete transposition of the great arteries in 2 patients, hypoplastic left heart syndrome in 1, Fallot type double-outlet right ventricle in 1, aortic coarctation with severe atrioventricular valve regurgitation in 1, and total anomalous pulmonary venous return in 1. Total repair and palliative repair were undertaken in each 3 patient. Result: Most patients showed vasodilatory shock not responding to the inotropes and required the vasopressin therapy within 24 hours after cardiac surgery and its readministration for septic shock. The dosing range for vasopressin was 0.0002∼0.008 unit/kg/minute with a median total time of its administration of 59 hours (ranges; 26∼140 hours). Systolic blood pressure before, 1 hour, and 6 hours after its administration were 42.7$\pm$7.4 mmHg, 53.7$\pm$11.4 mmHg, and 56.3$\pm$13.4 mmHg, respectively, which shows a significant increase in systolic blood pressure (systolic pressure 1hour and 6 hours after the administration compared to before the administration; p=0.042 in all). Inotropic indexes before, 6 hour, and 12 hours after its administration were 32.3$\pm$7.2, 21.0$\pm$8.4, and 21.2$\pm$8.9, respectively, which reveals a significant decrease in inotropic index (inotropic indexes 6 hour and 12 hours after the administration compared to before the administration; p=0.027 in all). Significant metabolic acidosis and decreased urine output related to systemic hypoperfusion were not found after vasopressin admin- istration. Conclusion: In young children suffering from vasodilatory shock not responding to common inotropes despite normal ventricular contractility, intravenous vasopressin reveals to be an effective vasoconstrictor to increase systolic blood pressure and to mitigate the complications related to higher doses of inotropes.

• Journal of Korean Society of Environmental Engineers
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• v.31 no.8
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• pp.673-678
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• 2009

High-rate phosphorous removal by PAC (poly aluminum chloride) coagulation of A2O effluent was investigate to meet the stringent requirement of wastewater discharge from municipal wastewater treatment plant. A series of jar tests were conducted to find optimum coagulation condition and to enhance removal efficiency. The optimum volumetric concentration of PAC was 30 ppm (2.81mol Al/mol P by mol ratio). Only 17.2% of soluble P was removed for 30 minutes' settling without PAC addition, while this increased to 30.3% by dosing 10ppm PAC. It even increased conspicuously from 49.3% to 88.4% by increasing PAC dose from 20 ppm to 30 ppm. 92.4% of total P was removed by 30 ppm PAC, and the effluent concentration (0.3 mg/L) was acceptable for discharge. The optimum value of coagulation time, settling time, and pH were 4minutes, 20 minutes, and 7.0, respectively. It was not necessary to control pH of raw sample whose pH was 7.0. Soluble P removal was remarkably enhanced at pH 7.0. This implied that sweep floc formation by $Al(OH)_3$ was the main mechanism of coagulation for soluble P removal. Influent and effluent of secondary clarifier were tested for coagulation, and the effluent was better for high-rate P removal. It resulted in 0.18 mg/L of P and 95.4% of P removal by coagulation. It was favorable to recycle the treated water to coagulation tank and the optimum recycle ratio was 0.3.

• Journal of Korean Society of Environmental Engineers
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• v.31 no.4
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• pp.263-271
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• 2009

This study evaluated the flocs forming characteristics in the mixing zone to increase the coagulation effect in the drinking water plant. As a measuring tool of formed flocs, on-line particle dispersion analyzer (iPDA) was used in Y drinking water plant. To evaluate the forming flocs, many parameters such as poly amine, coagulant dosing amount, raw water turbidity, and pH was applied in this study. During the periods of field test, poly aluminium chloride (PACl) as a coagulant was used. With the increase of the raw water turbidities, poly amine was also added as one of aids for increasing in coagulation efficiency. The turbidity and pH of raw water was ranged from 7 to 9 and from 25 to 140 NTU, respectively. The increasing of raw water turbidity brought the bigger floc sizes accordingly. From a regression analysis, $R^2$ value was 0.8040 as a function of T, raw water turbidity. Floc size index (FSI) was obtained from a correlation equation as follows; FSI = 0.9388logT - 0.3214 Also, polyamine gave the bigger flocs the moment it is added to the coagulated water in the rapid mixing zone. One of parameters influencing the floc sizes was the addition of powdered active carbon(PAC) in the mixing zone. In case of higher turbidity of raw water, $R^2$ value was 0.9050 in the parameters of [PACl] and [PAC]; FSI = $0.0407[T]^{0.324}[PACI]^{0.769}[PAC]^{0.178}$ On-line floc monitor was beneficial to evaluate the flocs sizes depending on the many parameters consisting raw water properties, bring the profitable basic data to control the mixing zone more effectively.

• Journal of Korean Society of Environmental Engineers
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• v.29 no.6
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• pp.715-721
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• 2007

Residual calcium concentration is high, in general, at the effluent of the fluoride removal process in the electronics industry manufacturing semiconductor and LCD. To increase the stability of the membrane process incorporated for reuse of wastewater, the residual calcium is required to be pre-removed. Hyperkinetic Vortex Crystallization(HVC) process was installed in the electronics industry manufecturing semi conductor as a pilot scale for accelerating calcification of calcium ion. Compared to the conventional soda ash method, the 31% higher calcium removal efficiency was achieved when HVC was applied at the same sodium carbonate dosage. In order to maintain the economic calcium removal target of 70% preset by manufacturer, the dosing concentration of the soda ash was 530 mg/L based on influent flowrate. The seed concentration in the reactor was one of the critical factors and should be maintained in the range of $800\sim1,200mg$ SS/L to maximize the calcium removal efficiency. The calcite production rate was 0.30 g SS/g $Na_2CO_3$ in the average. The economic HVC passing time of the mixture was in the range of $2\sim5$ times. Relatively, stable calcium concentration was maintained in the range of $30\sim72$ mg/L(average 49 mg/L) although the calcium concentration in the feed was severely fluctuated with $74\sim359$ mg/L(average 173 mg/L). The HVC process was characterized as environment-friendly technology reducing chemical dosage and chemical sludge production and minimizing maintenance cost.

• Journal of Food Hygiene and Safety
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• v.24 no.4
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• pp.352-356
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• 2009

The purpose of this study was to introduce the toxicological study review to evaluate the safety of PDMS on the 69th JECFA meeting. Polydimethylsiloxane is a polymer and its ADI was established at 23rd JECFA meeting in 1979. The ADI was maintained although the specification was expanded at its 26th, 29 th, 37 th meetings. Recently, it was reported that PDMS with low molecular weight and viscosity has high absorption rate and different toxicity, so it was submitted at 69th meeting. Toxicological studies of PDMS were submitted from the sponsor and additional information is collected from a document searching. The toxicological studies were reviewed in accordance with the 'Guidelines for the preparation of toxicological working papers for the Joint FAO/WHO Expert Committee on Food Additives'. In the available acute, sub-chronic and chronic toxicity studies on PDMS, dose-related increases in incidence and severity of ocular lesions(corneal crystal, inflammation of the corneal epithelium etc.) were consistently observed after oral dosing. It seems to be a local irritant effect, but the mechanism by which the ocular lesions arose is unclear, although the lack of absorption of PDMS indicates that it is unlikely to be a direct systemic effect. Consequently, the relevance of the ocular lesions for food use of PDMS could not be determined. The ADI of PDMS was re-established from 0-1.5 mg/kg bw/day to 0-0.8 mg/kg bw/day by applying additional safety factor 2 based on its ocular toxicity. The result of 0-0.8 mg/kg bw/day is a temporary ADI until further data are provided to 2010.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.17 no.4
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• pp.34-42
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• 2016

In order to prepare for the type approval test for the United States Coast Guard (USCG) Phase-II of Ballast Water Treatment System (BWTS), a phytoplankton mass culture was conducted in a mesocosm enclosure. We evaluated the response of the phytoplankton community after nutrient addition (+N, +P, and +NP) and investigated the development of the species with increasing culture time. After nutrient dosing, the phytoplankton population significantly (p < 0.05) increased from day 1 to day 3, depending on the nutrient treatments In particular, the specific growth rate of the phytoplankton community in the case of +NP treatment and + N treatment were estimated to be $2.47d^{-1}$ and $1.98d^{-1}$, respectively. The phytoplankton population density in the case of + NP treatment was approximately 50 times higher than that of the control group, suggesting that these treatments could be useful for mass culturing phytoplankton (> 75% of natural community) for the approval regulation of USCG Phase-II. In the phytoplankton community of the mesocosm, Pseudo-nitzchia spp. dominated in the logarithmic growth phase. The cell density decreased significantly (p < 0.05) with increasing time, coinciding with the nutrient limitation. At that time, the dominance of Pseudo-nitzchia spp. shifted to that of Cylindrotheca closterium. Therefore, the optimum nutrient concentration ($N:30{\mu}M$, $P:3{\mu}M$) and reasonable harvesting time (after 3 days in summer) found in this study for the mass culturing of phytoplankton may be helpful to meet the USCG Phase-II biological criteria to be used in BWTS.