• 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 the Korea Organic Resources Recycling Association
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• v.16 no.2
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• pp.29-37
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• 2008

In this work, it was investigated that various aspects of process, application situation, merits and short-coming results of the thermophilic methane fermentation with highly concentrated organic waste substances such as sewage sludges, food wastes and excretions. The merits of this methane fermentation were that it had a very fast reaction rate and was possible to proceed in high loads. It was also high in mortality for pathogenic microorganism and the digested sludge was more hygienic. However, the short-comings were that more energy was required for heating in the fermentation facility, no surplus energy could be gained from low concentration of organic waste, the fermentation treatment dropped level of water quality, thus burdens discharging process of water. Especially, the high concentration of methane fermentation could possibly lack nutritious salt and could face the disturbance by ${NH_4}^+-N$, a proper alternative was required. In general, thermophilic methane fermentation was considered as a better mean in disposing of cow excretion and food waste which were highly concentrated organic wastes. On the other hand, under the condition where the concentration of waste material was low and the high concentrate waste material became higher than 3,000 mg/L in ${NH_4}^+-N$, thermophilic methane fermentation resulted less desirable outcome.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.4
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• pp.445-451
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• 2008

The purpose of this study was carried out to examine the effects of onion kimchi extract supplementation on blood glucose level and serum lipid components in streptozotocin (STZ)-induced diabetic rats for 4 weeks. STZ was administered as a single dose (50 mg/kg BW) to induce diabetes, and the diabetic rats were divided into eight groups (normal, diabetic control, and six treatment groups). The dose of onion kimchi extract 100 (OK-100), 200 (OK-200), and 400 (OK-400) mg/kg/day or quercetin as a main compound of onion 5 (Q-5), 10 (Q-10), and 20 (Q-20) mg/kg/day were orally administered daily to STZ-induced diabetic rats for 4 weeks after STZ injection. The diabetic control rats (465.6 mg/dL) showed significantly higher blood glucose level than the normal rats (76.3 mg/dL) after 4 weeks, but was significantly reduced with onion kimchi extract and quercetin supplementation (p<0.001). Changes in body weight, kidney weight and urine volume were not significantly different in diabetic control rats, and in onion kimchi extract and quercetin treated rats. The serum total cholesterol levels of control were significantly decreased in onion kimchi extract and quercetin supplementation groups, respectively (p<0.001). The blood urea nitrogen level and urinary protein excretion in diabetic rats were not significant different among the groups. These results suggest that onion kimchi extract supplementation in STZ-induced diabetic rats may be a very important factor for the reduction of blood glucose and serum cholesterol profiles.

• Journal of East-West Nursing Research
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• v.1 no.1
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• pp.50-71
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• 1997

The intention of this study is to apprehend the con. tents and methods of herb remedies that are commonly conducted when there are health-problem cases of ENT, eyes, teeth and skin. Methods of this study are divided into two stages : 1) For a period of six months from December 1994 to June 1995, some 40 persons who are believed to be well versed with herb remedies have been randomly chosen, and we made a survey on herb remedies by symptoms: and 2) we have endeavored to make their grounds evident through the studies on literatures with the focus on the basic data collected. Their results are as follows: 1) When one feels a pain in ears, such herb remedies are employed as pouring the vapor into ears, which is made by steaming Alaska pollack, or as applying or wiping with the juices of radish or the ginkgo, or' alum. Applying the radish juice is effective for sterilization and fever removal: and applying the ginkgo juice is effective for cleanliness. But, plastering alum, sesame oil or castor oil, or pouring the vapor of Alaska pollack into ears are perhaps effective but do not have any pharmacologic grounds. 2) When one bleeds at the nose, such kinds of herb remedies are applied as stimulating nose or head with cold water, pressing nose or ridge of nose, or filling up nares with mashed mugworts. In addition, they have utilized garlic or leeks. Such methods as stimulating with cold water or just pressing nose and ridge of nose is based on reasonable grounds, i.e. vasoconstriction and vascular compression ; and applying mashed garlic on the sole of foot is good for the circulation of Qui ; and the use of mugworts and leeks is based upon the pharmacological function of hemostasis. 3) When one feels a sore throat such kinds of herb remedies are employed as gargling or rinsing throat with brine, drinking hot gruel or water, or drinking the juice of mugwort, radish, ginger or Chinese quince. Gargling with brine or drinking the juice of mugwort, radish or ginger is based upon the pharmacological function of pain alleviation, fever removal, and detoxication. 4) When a boil is formed in mouth, such herb remedies are applied as spreading honey, brine or alum water, and taking gall nut, Chinese matrimony vine, lotus root, etc, for drugs. Spreading honey, brine or water that is made by infusing gallnut, Chinese matrimony vine, lotus root is based upon such functions as hematosis, astriction, antibacterial, and antiphlogistic, Alum, eggplant and licorice are said to be effective, but their pharmacological effects have no grounds. 5) When one has conjunctivitis such herb remedies are commonly applied as irrigation with brine and dropping breast milk in eyes. Moreover, such other drugs are used as plantain. shepherd's purse, and purslane, etc. The use of brine, breast milk, plantain, shepherd's purse and purslane is based upon such functions as sterilization, antiphlogistic, disinfection and pain relieving. Eriocaulon sieboldianum, bean stem, bean pod and narcissus leaves are said to be effective, but their pharmacological action have no basis. When one has a stye, such herb remedies are applied as extracting eyelashes, stimulating by a massage of middle finger, third finger or big toe, as well as sear ing with a heated bamboo comb that is fine-toothed. Other than these, plantain and nightshade's nuts are used as drugs for it. Extracting eyelashes corresponds with exclusing suppurative node and draining the stye of pus ; and the use of plantain is based upon disinfection: and nightshade's nuts are said to be effective, however, their pharmacological action has no grounds. 6) For a treatment of toothache, such herb remedies are commonly employed as rinsing mouth with brine and holding cold water or gasoline in the mouth ; and as the drugs that are believed to be effective have been Welsh onion, ginger and castor-oil, plant, etc. The use of Welsh onion is based upon pain killing, antiinflammatory actions, and the use of ginger is based upon detoxication and disinfection ; and seeds of castor-oil plants are said to be effective, but they have no pharmacological basis. 7) When one has hives, such herb remedies are commonly applied as rubbing burned straw in affected parts, exposing to its smoke, rubbing with salt, sweeping down with a broom, and spreading and drinking boiled water of trifoliate orange. The use of cassia tora seeds, walnut, aloe and radish is said to be effective. The use of cassia tor a seeds has the functions of intestinal order, anti-paralysis, etc. The use of walnut has resulted in an increase of blood by invigorating spirits ; and the use of aloe is based upon disinfection, antibiotic, anti-salt, antihistamine and detoxication action. But, the effects of radish juice and straw's smoke have no pharmacological grounds. 8) When one gets a boil, such herb remedies are commonly used as applying a plaster, paste of flour mixed with yolk, soy sauce or honey, as well as spreading pounded elm tree. Other remedies that have been said to be effective are ; heating with mugwort, brine, wild rocambole, aloe, onion, squid's bone, etc. The use of mugwort is based upon pain killing, astringent antiinflammatory and tranquility. Wild rocambole is based upon the generation and maintenance functions of cell-joining textures ; elm tree upon antiphlogistic ; aloe upon fever removal and antiphlogistic ; onion on pain killing, fever removal, antiphlogistic and tranquility ; squid's bone on astriction: and brine or vinegar on sterilization. Pine resin and gardenia seed are said to be effective, but they have no pharmacological basis. 9) When one cuts his skin, such herb remedies are commonly employed as spreading mugwort's juice or squid's bone powder, or pressing the wounds. In addition, kalopanax, onion and fine soil are employed. The use of mugwort, kalopanax and squid's bone is based upon such functions as hemostasis, sedation, pain killing, antibacterial ; and fine soil is said to be effective, but it has no pharmacological basis. 10) When one suffers from whitlow, such herb remedies are commonly utilized as heating with boiled soy sauce, spreading soybean paste, or dipping into eggs, etc. Other drugs that have been employed are onion root, brine, eggplant, potato, loach, etc. The use of onion is based upon pain killing and antiphlogistic functions ; and that of brine upon antiphlogistic function. The use of soy sauce or soybean paste, fomentation, eggplant, potato and loach is said to be effective, but it has no pharmacblogic ground. 11) For the treatment of frostbite, such herb remedies are commonly used as dipping the affected part into frozen soybean sack, using boiled water of eggplant stem, garlic caulis, onion, hot pepper, caulis. Onion is based upon antiphlogistic and tranquility actions garlic upon disintection, metabolic exacerbation, tonic and aphrodisiac actions and the use of eggplant and hot pepper is based upon help blood circulation, dissolution and excretion of waste matters in vein. 12) For the treatment of burn, such herb remedies or drugs are commonly used as cleansing with Korean gin, spreading eggs, cleansing with cold water and soap water ; and as brine, cactus, moss, soybean paste, oil, etc. The cleansing with Korean gin, cold water, soap water, brine, vinegar is based upon cleaning and sterilizing functions ; and the use of cucumber is based upon nu. trition provision, and strengthening of resisting power by adjustment of metabolism. The use of potato, cactus, moss, oil and eggs is said to be effective, but their phamacological functions are not clarified. In view of the above results, we can realize that the drugs that have been employed in herb remedies are quite diverse. However, in regard to majority of herb remedies that have been employed by symptoms, the pharmacological functions of their drugs have not been clarified, and they are merely known as effective. Furthermore, they have not been recorded in the literature as yet ; and we confirm that there have been many herb remedies that were executed without the proper knowlege of their effects. It is now our view that the results of this survey may be utilized for consulting data in regard to the use of herb remedies.