• 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 Chest Surgery
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• v.39 no.12 s.269
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• pp.879-890
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• 2006

Background: The dysfunction of multiple organs is found to be caused by reactive oxygen species as a major modulator of microvascular injury after hemorrhagic shock. Hemorrhagic shock, one of many causes inducing acute lung injury, is associated with increase in alveolocapillary permeability and characterized by edema, neutrophil infiltration, and hemorrhage in the interstitial and alveolar space. Aggressive and rapid fluid resuscitation potentially might increased the risk of pulmonary dysfunction by the interstitial edema. Therefore, in order to improve the pulmonary dysfunction induced by hemorrhagic shock, the present study was attempted to investigate how to reduce the inflammatory responses and edema in lung. Material and Method: Male Sprague-Dawley rats, weight 300 to 350 gm were anesthetized with ketamine(7 mg/kg) intramuscular Hemorrhagic Shock(HS) was induced by withdrawal of 3 mL/100 g over 10 min. through right jugular vein. Mean arterial pressure was then maintained at $35{\sim}40$ mmHg by further blood withdrawal. At 60 min. after HS, the shed blood and Ringer's solution or 5% albumin was infused to restore mean carotid arterial pressure over 80 mmHg. Rats were divided into three groups according to rectal temperature level($37^{\circ}C$[normothermia] vs $33^{\circ}C$[mild hypothermia]) and resuscitation fluid(lactate Ringer's solution vs 5% albumin solution). Group I consisted of rats with the normothermia and lactate Ringer's solution infusion. Group II consisted of rats with the systemic hypothermia and lactate Ringer's solution infusion. Group III consisted of rats with the systemic hypothermia and 5% albumin solution infusion. Hemodynamic parameters(heart rate, mean carotid arterial pressure), metabolism, and pulmonary tissue damage were observed for 4 hours. Result: In all experimental groups including 6 rats in group I, totally 26 rats were alive in 3rd stage. However, bleeding volume of group I in first stage was $3.2{\pm}0.5$ mL/100 g less than those of group II($3.9{\pm}0.8$ mL/100 g) and group III($4.1{\pm}0.7$ mL/100 g). Fluid volume infused in 2nd stage was $28.6{\pm}6.0$ mL(group I), $20.6{\pm}4.0$ mL(group II) and $14.7{\pm}2.7$ mL(group III), retrospectively in which there was statistically a significance between all groups(p<0.05). Plasma potassium level was markedly elevated in comparison with other groups(II and III), whereas glucose level was obviously reduced in 2nd stage of group I. Level of interleukine-8 in group I was obviously higher than that of group II or III(p<0.05). They were $1.834{\pm}437$ pg/mL(group I), $1,006{\pm}532$ pg/mL(group II), and $764{\pm}302$ pg/mL(group III), retrospectively. In histologic score, the score of group III($1.6{\pm}0.6$) was significantly lower than that of group I($2.8{\pm}1.2$)(p<0.05). Conclusion: In pressure-controlled hemorrhagic shock model, it is suggested that hypothermia might inhibit the direct damage of ischemic tissue through reduction of basic metabolic rate in shock state compared to normothermia. It seems that hypothermia should be benefit to recovery pulmonary function by reducing replaced fluid volume, inhibiting anti-inflammatory agent(IL-8) and leukocyte infiltration in state of ischemia-reperfusion injury. However, if is considered that other changes in pulmonary damage and inflammatory responses might induce by not only kinds of fluid solutions but also hypothermia, and that the detailed evaluation should be study.

• Journal of the Korean Wood Science and Technology
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• v.2 no.2
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• pp.8-12
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• 1974

1. If one unity is given to the prongs whose ends touch each other for estimating the internal stresses occuring in it, the internal stresses which are developed in the open prongs can be evaluated by the ratio to the unity. In accordance with the above statement, an equation was derived as follows. For employing this equation, the prongs should be made as shown in Fig. I, and be measured A and B' as indicated in Fig. l. A more precise value will result as the angle (J becomes smaller. $CH=\frac{(A-B') (4W+A) (4W-A)}{2A[(2W+(A-B')][2W-(A-B')]}{\times}100%$ where A is thickness of the prong, B' is the distance between the two prongs shown in Fig. 1 and CH is the value of internal stress expressed by percentage. It precision is not required, the equation can be simplified as follows. $CH=\frac{A-B'}{A}{\times}200%$ 2. Under scheduled drying condition III the kiln, when the weight of a sample board is constant, the moisture content of the shell of a sample board in the case of a normal casehardening is lower than that of the equilibrium moisture content which is indicated by the Forest Products Laboratory, U. S. Department of Agriculture. This result is usually true, especially in a thin sample board. A thick unseasoned or reverse casehardened sample does not follow in the above statement. 3. The results in the comparison of drying rate with five different kinds of wood given in Table 1 show that the these drying rates, i.e., the quantity of water evaporated from the surface area of I centimeter square per hour, are graded by the order of their magnitude as follows. (1) Ginkgo biloba Linne (2) Diospyros Kaki Thumberg. (3) Pinus densiflora Sieb. et Zucc. (4) Larix kaempheri Sargent (5) Castanea crenata Sieb. et Zucc. It is shown, for example, that at the moisture content of 20 percent the highest value revealed by the Ginkgo biloba is in the order of 3.8 times as great as that for Castanea crenata Sieb. & Zucc. which has the lowest value. Especially below the moisture content of 26 percent, the drying rate, i.e., the function of moisture content in percentage, is represented by the linear equation. All of these linear equations are highly significant in testing the confficient of X i. e., moisture content in percentage. In the Table 2, the symbols are expressed as follows; Y is the quantity of water evaporated from the surface area of 1 centimeter square per hour, and X is the moisture content of the percentage. The drying rate is plotted against the moisture content of the percentage as in Fig. 2. 4. One hundred times the ratio(P%) of the number of samples occuring in the CH 4 class (from 76 to 100% of CH ratio) within the total number of saplmes tested to those of the total which underlie the given SR ratio is measured in Table 3. (The 9% indicated above is assumed as the danger probability in percentage). In summarizing above results, the conclusion is in Table 4. NOTE: In Table 4, the column numbers such as 1. 2 and 3 imply as follows, respectively. 1) The minimum SR ratio which does not reveal the CH 4, class is indicated as in the column 1. 2) The extent of SR ratio which is confined in the safety allowance of 30 percent is shown in the column 2. 3) The lowest limitation of SR ratio which gives the most danger probability of 100 percent is shown in column 3. In analyzing above results, it is clear that chestnut and larch easly form internal stress in comparison with persimmon and pine. However, in considering the fact that the revers, casehardening occured in fir and ginkgo, under the same drying condition with the others, it is deduced that fir and ginkgo form normal casehardening with difficulty in comparison with the other species tested. 5. All kinds of drying defects except casehardening are developed when the internal stresses are in excess of the ultimate strength of material in the case of long-lime loading. Under the drying condition at temperature of $170^{\circ}F$ and the lower humidity. the drying defects are not so severe. However, under the same conditions at $200^{\circ}F$, the lower humidity and not end coated, all sample boards develop severe drying defects. Especially the chestnut was very prone to form the drying defects such as casehardening and splitting.

• Proceedings of the KOR-KST Conference
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• 1995.02a
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• pp.101-113
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• 1995

The objective of this research is to test the feasibility of developing a statewide truck traffic forecasting methodology for Wisconsin by using Origin-Destination surveys, traffic counts, classification counts, and other data that are routinely collected by the Wisconsin Department of Transportation (WisDOT). Development of a feasible model will permit estimation of future truck traffic for every major link in the network. This will provide the basis for improved estimation of future pavement deterioration. Pavement damage rises exponentially as axle weight increases, and trucks are responsible for most of the traffic-induced damage to pavement. Consequently, forecasts of truck traffic are critical to pavement management systems. The pavement Management Decision Supporting System (PMDSS) prepared by WisDOT in May 1990 combines pavement inventory and performance data with a knowledge base consisting of rules for evaluation, problem identification and rehabilitation recommendation. Without a r.easonable truck traffic forecasting methodology, PMDSS is not able to project pavement performance trends in order to make assessment and recommendations in the future years. However, none of WisDOT's existing forecasting methodologies has been designed specifically for predicting truck movements on a statewide highway network. For this research, the Origin-Destination survey data avaiiable from WisDOT, including two stateline areas, one county, and five cities, are analyzed and the zone-to'||'&'||'not;zone truck trip tables are developed. The resulting Origin-Destination Trip Length Frequency (00 TLF) distributions by trip type are applied to the Gravity Model (GM) for comparison with comparable TLFs from the GM. The gravity model is calibrated to obtain friction factor curves for the three trip types, Internal-Internal (I-I), Internal-External (I-E), and External-External (E-E). ~oth "macro-scale" calibration and "micro-scale" calibration are performed. The comparison of the statewide GM TLF with the 00 TLF for the macro-scale calibration does not provide suitable results because the available 00 survey data do not represent an unbiased sample of statewide truck trips. For the "micro-scale" calibration, "partial" GM trip tables that correspond to the 00 survey trip tables are extracted from the full statewide GM trip table. These "partial" GM trip tables are then merged and a partial GM TLF is created. The GM friction factor curves are adjusted until the partial GM TLF matches the 00 TLF. Three friction factor curves, one for each trip type, resulting from the micro-scale calibration produce a reasonable GM truck trip model. A key methodological issue for GM. calibration involves the use of multiple friction factor curves versus a single friction factor curve for each trip type in order to estimate truck trips with reasonable accuracy. A single friction factor curve for each of the three trip types was found to reproduce the 00 TLFs from the calibration data base. Given the very limited trip generation data available for this research, additional refinement of the gravity model using multiple mction factor curves for each trip type was not warranted. In the traditional urban transportation planning studies, the zonal trip productions and attractions and region-wide OD TLFs are available. However, for this research, the information available for the development .of the GM model is limited to Ground Counts (GC) and a limited set ofOD TLFs. The GM is calibrated using the limited OD data, but the OD data are not adequate to obtain good estimates of truck trip productions and attractions .. Consequently, zonal productions and attractions are estimated using zonal population as a first approximation. Then, Selected Link based (SELINK) analyses are used to adjust the productions and attractions and possibly recalibrate the GM. The SELINK adjustment process involves identifying the origins and destinations of all truck trips that are assigned to a specified "selected link" as the result of a standard traffic assignment. A link adjustment factor is computed as the ratio of the actual volume for the link (ground count) to the total assigned volume. This link adjustment factor is then applied to all of the origin and destination zones of the trips using that "selected link". Selected link based analyses are conducted by using both 16 selected links and 32 selected links. The result of SELINK analysis by u~ing 32 selected links provides the least %RMSE in the screenline volume analysis. In addition, the stability of the GM truck estimating model is preserved by using 32 selected links with three SELINK adjustments, that is, the GM remains calibrated despite substantial changes in the input productions and attractions. The coverage of zones provided by 32 selected links is satisfactory. Increasing the number of repetitions beyond four is not reasonable because the stability of GM model in reproducing the OD TLF reaches its limits. The total volume of truck traffic captured by 32 selected links is 107% of total trip productions. But more importantly, ~ELINK adjustment factors for all of the zones can be computed. Evaluation of the travel demand model resulting from the SELINK adjustments is conducted by using screenline volume analysis, functional class and route specific volume analysis, area specific volume analysis, production and attraction analysis, and Vehicle Miles of Travel (VMT) analysis. Screenline volume analysis by using four screenlines with 28 check points are used for evaluation of the adequacy of the overall model. The total trucks crossing the screenlines are compared to the ground count totals. L V/GC ratios of 0.958 by using 32 selected links and 1.001 by using 16 selected links are obtained. The %RM:SE for the four screenlines is inversely proportional to the average ground count totals by screenline .. The magnitude of %RM:SE for the four screenlines resulting from the fourth and last GM run by using 32 and 16 selected links is 22% and 31 % respectively. These results are similar to the overall %RMSE achieved for the 32 and 16 selected links themselves of 19% and 33% respectively. This implies that the SELINICanalysis results are reasonable for all sections of the state.Functional class and route specific volume analysis is possible by using the available 154 classification count check points. The truck traffic crossing the Interstate highways (ISH) with 37 check points, the US highways (USH) with 50 check points, and the State highways (STH) with 67 check points is compared to the actual ground count totals. The magnitude of the overall link volume to ground count ratio by route does not provide any specific pattern of over or underestimate. However, the %R11SE for the ISH shows the least value while that for the STH shows the largest value. This pattern is consistent with the screenline analysis and the overall relationship between %RMSE and ground count volume groups. Area specific volume analysis provides another broad statewide measure of the performance of the overall model. The truck traffic in the North area with 26 check points, the West area with 36 check points, the East area with 29 check points, and the South area with 64 check points are compared to the actual ground count totals. The four areas show similar results. No specific patterns in the L V/GC ratio by area are found. In addition, the %RMSE is computed for each of the four areas. The %RMSEs for the North, West, East, and South areas are 92%, 49%, 27%, and 35% respectively, whereas, the average ground counts are 481, 1383, 1532, and 3154 respectively. As for the screenline and volume range analyses, the %RMSE is inversely related to average link volume. 'The SELINK adjustments of productions and attractions resulted in a very substantial reduction in the total in-state zonal productions and attractions. The initial in-state zonal trip generation model can now be revised with a new trip production's trip rate (total adjusted productions/total population) and a new trip attraction's trip rate. Revised zonal production and attraction adjustment factors can then be developed that only reflect the impact of the SELINK adjustments that cause mcreases or , decreases from the revised zonal estimate of productions and attractions. Analysis of the revised production adjustment factors is conducted by plotting the factors on the state map. The east area of the state including the counties of Brown, Outagamie, Shawano, Wmnebago, Fond du Lac, Marathon shows comparatively large values of the revised adjustment factors. Overall, both small and large values of the revised adjustment factors are scattered around Wisconsin. This suggests that more independent variables beyond just 226; population are needed for the development of the heavy truck trip generation model. More independent variables including zonal employment data (office employees and manufacturing employees) by industry type, zonal private trucks 226; owned and zonal income data which are not available currently should be considered. A plot of frequency distribution of the in-state zones as a function of the revised production and attraction adjustment factors shows the overall " adjustment resulting from the SELINK analysis process. Overall, the revised SELINK adjustments show that the productions for many zones are reduced by, a factor of 0.5 to 0.8 while the productions for ~ relatively few zones are increased by factors from 1.1 to 4 with most of the factors in the 3.0 range. No obvious explanation for the frequency distribution could be found. The revised SELINK adjustments overall appear to be reasonable. The heavy truck VMT analysis is conducted by comparing the 1990 heavy truck VMT that is forecasted by the GM truck forecasting model, 2.975 billions, with the WisDOT computed data. This gives an estimate that is 18.3% less than the WisDOT computation of 3.642 billions of VMT. The WisDOT estimates are based on the sampling the link volumes for USH, 8TH, and CTH. This implies potential error in sampling the average link volume. The WisDOT estimate of heavy truck VMT cannot be tabulated by the three trip types, I-I, I-E ('||'&'||'pound;-I), and E-E. In contrast, the GM forecasting model shows that the proportion ofE-E VMT out of total VMT is 21.24%. In addition, tabulation of heavy truck VMT by route functional class shows that the proportion of truck traffic traversing the freeways and expressways is 76.5%. Only 14.1% of total freeway truck traffic is I-I trips, while 80% of total collector truck traffic is I-I trips. This implies that freeways are traversed mainly by I-E and E-E truck traffic while collectors are used mainly by I-I truck traffic. Other tabulations such as average heavy truck speed by trip type, average travel distance by trip type and the VMT distribution by trip type, route functional class and travel speed are useful information for highway planners to understand the characteristics of statewide heavy truck trip patternS. Heavy truck volumes for the target year 2010 are forecasted by using the GM truck forecasting model. Four scenarios are used. Fo~ better forecasting, ground count- based segment adjustment factors are developed and applied. ISH 90 '||'&'||' 94 and USH 41 are used as example routes. The forecasting results by using the ground count-based segment adjustment factors are satisfactory for long range planning purposes, but additional ground counts would be useful for USH 41. Sensitivity analysis provides estimates of the impacts of the alternative growth rates including information about changes in the trip types using key routes. The network'||'&'||'not;based GMcan easily model scenarios with different rates of growth in rural versus . . urban areas, small versus large cities, and in-state zones versus external stations. cities, and in-state zones versus external stations.