• 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.

• Tuberculosis and Respiratory Diseases
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• v.48 no.1
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• pp.14-23
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• 2000

Background: The evaluation of candidates for successful lung resection is important. Our study was conducted to determine the preoperative predictors of postoperative mortality and morbidity in lung cancer patients with impaired lung function. Method; Between October 1, 1995 and August 31, 1997, 36 lung resection candidates for lung cancer with $FEV_1$ of less than 2L or 60% of predicted value were included prospectively. Age, sex, weight loss, hematocrit, serum albumin, EKG and concomitant illness were considered as systemic potential predictors for successful lung resection. Smoking history, presence of pneumonia, dyspnea scale(l to 4), arterial blood gas analysis with room air breathing, routine pulmonary function test were also included for the analysis. In addition, predicted postoperative(ppo) pulmonary factors such as ppo-$FEV_1$ ppo-diffusing capacity(DLco), predicted postoperative product(PPP) of ppo-$FEV_1%{\times}$ppo-DLco% and ppo-maximal $O_2$ uptake($VO_2$max) were also measured. Results: There were 31 men and 5 women with the median age of 65 years(range, 44 to 82) and a mean $FEV_1$ of $1.78{\pm}0.06L$. Pneumonectomy was performed in 14 patients, bilobectomy in 8, lobectomy in 14. Pulmonary complications developed in 10 patients; cardiac complications in 3, other complications(empyema, air leak, bleeding) in 4. Twelve patients were managed in the intensive care unit for more than 48 hours. Two patients died within 30 days after operation. The ppo-$VO_2$max was less than 10 ml/kg/min in these two patients. MVV was the only predictor for the pulmonary complications. However, there was no predictor for the post operative death in this study. Conclusions: Based on the results, MVV was the useful predictor for postoperative pulmonary complications in lung cancer resection candidates with impaired lung function In addition, ppo-$VO_2$max value less than 10 ml/kg/min was associated with postoperative death, so exercise pulmonary function test could be useful as preoperative test. But further studies are needed to validate this result.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.367-375
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• 1998

Purpose : Xerostomia is a complication met by almost all patients who have radiotherapy for cancers of head and neck. Many studies for prevention of xerostomia will be necessary. Radiation-induced acute response of salivary glands has been defined as interphase death or apoptosis. Increased intracellular calcium level have an important role in radiation-induced apoptosis. Calcium channel blocker may prevent radiation-induced apoptosis of salivary glands. This study was designed to evaluate the effectiveness of diltiazem known as calcium channel blocker and pentoxifylline with inhibition of inflammatory response on the apoptosis as an acute response of radiation in rat salivary glands. Materials and Methods : Sprague-Dawley rats with about body weight 200-250 g were divided into 5 study groups : control, radiation alone, diltiazem with radiation, pentoxifylline with radiation, and diltiazem and pentoxifylline with radiation. The diltiazen and pentoxifylline were injected intraperitoneally 20 mg/kg and 50 mg/kg, 30 and 20 mimute before irradiation. respectively. Irradiation was given with a 4 MV linear accelerator. The 1600 cGy of radiation was delivered in a single fraction through a single anterior portal encompassing the entire neck. After 24 h of irradiation, rats were sacrificed and parotid and submandibular glands were removed and stained with hematoxylin and eosin. The quantification of apoptosis was performed by microscopic examination of stained tissue sections at a magnification of 200X and the percentage of apoptotic cell was calculated. Results : On parotid glands, the percentage of apoptosis by radiation alone, diltiazem with radiation, pentoxifylline with radiation, and diltiazem and pentoxifylline with radiation were 1.72$\%$ (8.35/486), 0.64$\%$ (2.9/453), 0.23$\%$ (1.2/516), and 0.28$\%$ (1.1/399), respectively. The apoptosis was markedly reduced in the groups receiving drugs compared with groups receivinge, radiation alone (p<0.05). In serous cell of submandibular glands, the percentages of apoptosis of radiation alone, diltiazem with radiation, pentoxifylline with radiation, and diltiazem and pentoxifylline with radiation were 1.94$\%$ (l1/567), 0.34$\%$ (1.9/554), 0.28$\%$ (1.8/637), and 0.22$\%$ (1.3/601), respectively. In the mucus cell of submandibular glands, the percentages of apoptosis were 0.92$\%$ (5.1/552), 0.41$\%$ (2.5/612), 0.29$\%$ (1.3/455), and 0.18$\%$ (1.0/562), respectively. The apoptosis was markedly reduced in the serous glands (p<0.05), but there was no difference in development of apoptosis in each group of mucus gland. Conclusion : These results suggest that radiation-induced apoptosis of serous cells of salivary glands may be decreased by diltiazem and pentoxifylline administration.

• KSBB Journal
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• v.29 no.4
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• pp.285-296
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• 2014

Although the problems of the algal blooms have been world-widely observed in freshwater, estuary, and marine throughout the year, it is not yet certain what are the basic causes of such blooms. Consequently, it is very difficult to predict when and where algal blooms occur. The constituents of the Asian dust are in a good agreement with the elements required for the algal growth, which suggests some possible relationship between the algal blooms and the Asian dust. There have been frequently algal blooms in drinking water from rivers or lakes. However, there is no any algal blooms in upwelling waters where the Asian dust cannot penetrate into the soil due to its relatively weak settling velocity (size of particles, $4.5{\pm}1.5{\mu}m$), which implies the possible close relationship of the Asian dust with algal blooms. The present initiative study is thus intended firstly in Korea to illustrate such a relationship by reviewing typical previous studies along with 12 years of weekly iron profiles (2001~2012) and two slant culture experiments with the dissolved Asian dust. The result showed bacterial suspected colonies in the slant culture experiment that are qualitatively in a good agreement with the recent Japanese studies. Since the diatoms require cheap energy (8%) compared to other phytoplankton (100%) to synthesize their cell walls by silicate, the present results can be used to predict algal blooms by diatoms if the concentrations of iron and silicate are available during spring and fall. It can be postulated that the algal blooms occur only if the environmental factors such as light, nutrients, calm water surface layer, temperature, and pH are simultaneously satisfied with the requirements of the micronutrients of mineral ions supplied by the Asian dust as enzymatic cofactors for the rapid bio-synthesis of the macromolecules during algal blooms. Simple eco-friendly methods to regulate the algal blooms are suggested for the initial stage of blooming with limited area: 1) to cover up the water surface with black curtain and inhibit photosynthesis during the day time, 2) to blow air (20.9%) or pure oxygen into the bottom of the water and inhibit rubisco for carbon uptake and nitrate reductase for nitrogen uptake activities in algal growth during the night, 3) to eliminate the resting spores or cysts by suction of bottom sediments as deep as 5 cm to prevent the next year germinations.

• Progress in Medical Physics
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• v.13 no.4
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• pp.209-217
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• 2002

There have been many studies on the application of the reciprocal advantages of multimodality image to define accurate target volume in the Process of radiation treatment planning. For the proper use of the multimodality images, the registration works between different modality images should be performed in advance. In this study, we selected chamfer matching method and mutual information method as most popular methods in recent image registration studies considering the registration accuracy and clinical practicality. And the two registration methods were analyzed to deduce the optimal registration method according to the characteristics of images. Lung phantom of which multimodality images could be acquired was fabricated and CT, MRI and SPECT images of the phantom were used in this study. We developed the registration program which can perform the two registration methods properly and analyzed the registration results which were produced by the developed program in many different images' conditions. Although the overall accuracy of the registration in both chamfer matching method and mutual information method was acceptable, the registration errors in SPECT images which had lower resolution and in degraded images of which data were removed in some part were increased when chamfer matching method was applied. Especially in the case of degraded reference image, chamfer matching methods produce relatively large errors compared with mutual information method. Mutual information method can be estimated as more robust registration method than chamfer matching method in this study because it did not need the prerequisite works, the extraction of accurate contour points, and it produced more accurate registration results consistently regardless of the images' characteristics. The analysis of the registration methods in this study can be expected to provide useful information to the utilization of multimodality images in delineating target volume for radiation treatment planning and in many other clinical applications.

• Korean Journal of Food Science and Technology
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• v.43 no.2
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• pp.161-168
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• 2011

The purpose of this study was to evaluate microbiological contamination of fresh vegetables in Korea. Twenty types of vegetables were tested for total aerobic bacteria, coliforms, Escherichia coli, yeast and mold, and pathogenic bacteria such as Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Salmonella, E. coli O157:H7, Cronobacter sakazakii, Shigella, and Campylobacter. Levels of total aerobic bacteria and coliform on 20 vegetables were between 3.74 and 8.04 log CFU/g, and 0.16 and 5.02 log CFU/g, respectively. The highest contamination levels of total aerobic bacteria were observed on water dropwort, sprouts, mungbean sprout, and ballflower root. There was no significant difference (p>0.05) in microbial contamination levels of total aerobic count, coliform, E. coli, yeast and mold between organic and nonorganic vegetables. When isolation methods using selective agars were applied, L. monocytogenes, B. cereus, Salmonella and Campylobacter were isolated from some fresh vegetable samples. Results of API kit tests showed that L. monocytogenes was identified on Chinese cabbage, cucumber, soybean sprouts, and iceberg lettuce while Salmonella was identified on Korean leek. Furthermore, Campylobacter jejuni was also identified in more than 50 of the 100 samples. However, when positive samples from API kit were tested for real-time PCR or 16S rRNA sequencing method, only B. cereus from perilla leaf, carrot, water dropwort, and sprouts showed positive results. These results indicate that selective agar and API kit detection methods might result in false positive results for some pathogens. Therefore, studies need to improve isolation or confirmation methods for such pathogens.

• Proceedings of the Korean Society of Postharvest Science and Technology of Agricultural Products Conference
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• 2004.10a
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• pp.67-72
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• 2004

Quality of fresh-cut tomato slices was compared during cold storage under various modified atmosphere packaging conditions. Chilling injury of slices in containers sealed with Film A was higher than with Film B; these films had oxygen transmission rates of 87.4 and 60.0 ml $h^{-1}\;m^{-2}\;atm^{-1}$ at $5^{\circ}C\;and\;99\%$ RH, respectively. While slices in containers with an initial atmospheric composition of air, $4\%\;CO_2+1\;or\;20\%\;O_2,\;8\%\;CO_2+1\;or\;20\%\;O_2,\;or\;12\%\;CO_2+20\%\;O_2$ showed fungal growth, slices in containers with $12\%\;CO_2+1\%\;O_2$ did not. Low ethylene in containers enhanced chilling injury. Modified atmosphere packaging provided good quality tomato slices with a shelf-life of 2 weeks or more at $5^{\circ}C$. Experiments were conducted to compare changes in quality of slices of red tomato (Lycopersicon esculentum Mill. 'Sunbeam') fruit from plants grown using black polyethylene or hairy vetch mulches under various foliar disease management systems including: no fungicide applications (NF), a disease forecasting model (Tom-Cast), and weekly fungicide applications (WF), during storage at $5^{\circ}C$ under a modified atmosphere. Slices were analyzed for firmness, soluble solids content (SSC), titratable acidity (TA), pH, electrolyte leakage, fungi, yeasts, and chilling injury. With both NF and Tom-Cast fungicide treatments, slices from tomato fruit grown with hairy vetch (Vicia villosa Roth) mulch were firmer than those from tomato fruit grown with black polyethylene mulch after 12 days storage. Ethylene production of slices from fruit grown using hairy vetch mulch under Tom-Cast was about 1.5- and 5-fold higher than that of slices from WF and NF fungicide treatments after 12 days, respectively. The percentage of water-soaked areas (chilling injury) for slices from tomato fruit grown using black polyethylene mulch under NF was over 7-fold that of slices from tomato fruit grown using hairy vetch under Tom-Cast. When stored at $20^{\circ}C$, slices from light-red tomato fruit grown with black polyethylene or hairy vetch mulches both showed a rapid increase in electrolyte leakage beginning 6 hours after slicing. However, slices from tomato fruit grown using the hairy vetch mulch tended to have lower electrolyte leakage than those grown with black polyethylene mulch. These results suggest that tomato fruit from plants grown using hairy vetch mulch may be more suitable for fresh-cut slices than those grown using black polyethylene mulch. Also, use of the disease forecasting model Tom-Cast, which can result in lower fungicide application than is currently used commercially, resulted in high quality fruit for fresh-cut processing. Experiments were conducted to determine if ethylene influences chilling injury, as measured by percentage of slices exhibiting water-soaked areas in fresh-cut tomato slices of 'Mountain Pride' and 'Sunbeam' tomato (Lycopersicon esculentum Mill.). Ethylene concentration in containers without ventilation significantly increased during storage at $5^{\circ}C$, whereas little or no accumulation of ethylene occurred in containers with one or six perforations. Chilling injury was greatest for slices in containers with six perforations, compared to slices in containers with one perforation, and was over 13-fold greater than that of slices in control containers with no perforations. An experiment was also performed to investigate the effectiveness of including an ethylene absorbent pad in containers on subsequent ethylene accumulation and chilling injury. While ethylene in the no-pad controls increased continually during storage of both 'Mountain Pride' and 'Sunbeam' tomatoes at $5^{\circ}C$ under modified atmosphere conditions, no increase in accumulation of ethylene was observed in containers containing ethylene absorbent pads throughout storage. The ethylene absorbent pad treatment resulted in a significantly higher percentage of chilling injury compared with the no-pad control. In studies aimed at inhibiting ethylene production using AVG during storage of slices, the concentration of ethylene in control containers (no AVG) remained at elevated levels throughout storage, compared to containers with slices treated with AVG. Chilling injury in slices treated with AVG was 5-fold greater than that of controls. Further, we tested the effect of ethylene pretreatment of slices on subsequent slice shelf-life and quality. In slices treated with ethylene (0, 0.1, 1, or $10\;{mu}L\;L^{-1}$) immediately after slicing, ethylene production in non-treated controls was greater than that of all other ethylene pre-treatments. However, pretreatment of slices 3 days after slicing resulted in a different pattern of ethylene production during storage. Ihe rate of ethylene production by slices treated with 1 L $L^{-1}$ ethylene 3 days after slicing was greater during storage than any of the other ethylene treatments. With slices pre-treated with ethylene, both immediately and 3 days after slicing, the rate of ethylene production tended to show an negative correlation with chilling injury. Chemical name used: 1-aminoethoxyvinylglycine (AVG).

• Korean Journal of Weed Science
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• v.3 no.2
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• pp.174-189
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• 1983

Experiments were conducted to evaluate the herbicidal characteristics of pyrazolate [4-(2,4-dichloro benzoyl)-1,3-dimethylpyrazol-5-yl-p-toluene-sulphonate] in greenhouse and lowland rice field. Pyrazolate controlled effectively most of annual weeds and such perennial weeds as Sagittaria pygmaea MIQ., Potamogeton distinctus A. BENN, Sagittaria trifolia L., Cyperus serotinus ROTTB, and Scirpus hotarui OHWI., whereas Eleocharis kuroguwai OHWI. was tolerent to pyrazolate. Although pyrazolate was applied at 2 to 10 days after transplanting, there was no difference in weed control The weeding effect was not influenced by percolation, depth of water and soil type. No difference in crop injury of rice was found with various levels of seedling age, transplanting depth, percolation, depth of water, soil type and time of application. When combined with butachlor, the mixture gave the same effect on rice phytotoxicity and weed control as pyrazolate alone did. Pyrazolate moved 1 to 2cm downward in lowland soil regardless of soil type and percolation. The herbicidal activity of pyrazolate persisted in soil for 60 to 90 days, depending on soil type, percolation and presence of soil microorganism.

• Korean Journal of Heritage: History & Science
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• v.56 no.3
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• pp.158-171
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• 2023

Pottery filled with organic materials was excavated from the G-2 building site of Yongjangseong Fortress, Jingo, a relic of the Goryeo Dynasty. In this study, the characteristics of organic material were confirmed by a scientific analysis of organic material in pottery found at the palace in Yongjangseong, Jindo. In addition, it was intended to review the analysis method to identify the natural resin and to secure characteristic components(biomarkers) for each natural resin and use them as basic data in the future. The organic materials in the pottery were analyzed using attenuated total reflectance Fourier-transformed infrared spectroscopy(ATR-FTIR) and gas chromatography mass spectrometry(GC-MS). The infrared spectral characteristics were estimated to be natural resin, and biomarkers of organic materials were identified as sesquiterpene-based compounds(C₁₅H₂₄, MW 204) and derivatives. The lacquer(T.vemicifluum) is composed mainly of alkenes, alkanes, and catechol. Pine resin(P.densiflora), on the other hand, is primarily composed of diterpenoid(abietic acid, pimaric acid) and Whangchil(yellow lacquer) is identified to have sesquiterpenes(such as selinene, muurolene, calamenene) as its main components. So, the organic material in the pottery can be identified as Whangchil by comparing their compounds with modern resin materials from Dendropanax. morbifera that correspond with the results. Whangchil, which is exuded from the Dendropanax. morbifera, has been used as a natural coating materials since ancient times, and it has been confirmed that the characteristic components are well preserved even 700 years later. It can be assumed that the interior Whangchil was stored not for use as a coating, but rather for ritual purposes when the building was constructed, because the pottery was found near the cornerstone. Furthermore, based on simplified sample preparation using pyrolysis-gas chromatography mass spectrometry(Py-GC-MS), the thermal decomposition products were found to be similar to the characteristic components, suggesting that this method can be applied to the identification of natural resins used in historic artifacts.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.452-461
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• 1994

Background: Tumor necrosis factor(TNF)-$\alpha$ and Interleukin(lL)-$1{\beta}$ are thought to play a major role in the pathogenesis of the septic syndrome, which is frequently associated with adult respiratory distress syndrome(ARDS). In spite of many reports for the role of TNF-$\alpha$ in the pathogenesis of ARDS, including human studies, it has been reported that TNF-$\alpha$ is not sensitive and specific marker for impending ARDS. But there is a possibility that the results were affected by the diversity of pathogenetic mechanisms leading to the ARDS because of various underlying disorders of the study group in the previous reports. The purpose of the present study was to evaluate the roles of TNF-$\alpha$ and IL-$1{\beta}$ as a predictable marker for development of ARDS in the patients with septic syndrome, in which the pathogenesis is believed to be mainly cytokine-mediated. Methods: Thirty-six patients of the septic syndrome hospitalized in the intensive care units of the Asan Medical Center were studied. Sixteens suffered from ARDS, whereas the remaining 20 were at the risk of developing ARDS(acute hypoxemic respiratory failure, AHRF). In all patients venous blood samples were collected in heparin-coated tubes at the time of enrollment, at 24 and 72 h thereafter. TNF-$\alpha$ and IL-$1{\beta}$ was measured by an enzyme-linked immunosorbent assay (ELISA). All data are expressed as median with interquartile range. Results: 1) Plama TNF-$\alpha$ levels: Plasma TNF-$\beta$ levels were less than 10pg/mL, which is lowest detection value of the kit used in this study within the range of the $mean{\pm}2SD$, in all of the normal controls, 8 of 16 subjects of ARDS and in 8 in 20 subjects of AHRF. Plasma TNF-$\alpha$ levels from patients with ARDS were 10.26pg/mL(median; <10-16.99pg/mL, interquartile range) and not different from those of patients at AHRF(10.82, <10-20.38pg/mL). There was also no significant difference between pre-ARDS(<10, <10-15.32pg/mL) and ARDS(<10, <10-10.22pg/mL). TNF-$\alpha$ levels were significantly greater in the patients with shock than the patients without shock(12.53pg/mL vs. <10pg/mL) (p<0.01). There was no statistical significance between survivors(<10, <10-12.92pg/mL) and nonsurvivors(11.80, <10-20.8pg/mL) (P=0.28) in the plasma TNF-$\alpha$ levels. 2) Plasma IL-$1{\beta}$ levels: Plasma IL-$1{\beta}$ levels were less than 0.3ng/mL, which is the lowest detection value of the kit used in this study, in one of each patients group. There was no significant difference in IL-$1{\beta}$ levels of the ARDS(2.22, 1.37-8.01ng/mL) and of the AHRF(2.13, 0.83-5.29ng/mL). There was also no significant difference between pre-ARDS(2.53, <0.3-8.34ngfmL) and ARDS(5.35, 0.66-11.51ng/mL), and between patients with septic shock and patients without shock (2.51, 1.28-8.34 vs 1.46, 0.15-2.13ng/mL). Plasma IL-$1{\beta}$ levels were significantly different between survivors(1.37, 0.4-2.36ng/mL) and nonsurvivors(2.84, 1.46-8.34ng/mL). Conclusion: Plasma TNF-$\alpha$ and IL-$1{\beta}$ level are not a predictable marker for development of ARDS. But TNF-$\alpha$ is a marker for shock in septic syndrome. These result could not exclude a possibility of pathophysiologic roles of TNF-$\alpha$ and IL-$1{\beta}$ in acute lung injury because these cytokine could be locally produced and exert its effects within the lungs.