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This paper presents the robust control scheme of improving the poor tracking performance owing to the defects of the time-delayed control (TDC) for robot manipulators. The defects of TDC include inaccurate estimation of an inertia matrix model and joint accelerations required to formulate the TDC scheme. The accuracy of estimating the inertia matrix and accelerations plays an important role in the control performance as well as the stability of TDC. To improve the estimation, the inertia matrix is identified by the recursive least square (RLS) method and the acceleration signals are estimated by a state observer (SOB). Tracking control performances of a manipulator by the proposed scheme are empirically tested and compared.

The time-delayed control (TDC) requires the inertia model and acceleration signals as well as the previous torque information of the robot manipulator. Performances of TDC depends on the accuracy of the estimation of inertia and acceleration signal. Therefore, more accurate estimation of necessary information is aimed. In this paper, the joint models of a robot manipulator are identified by RLS algorithm, which is based on a data driven approach from random inputs. A corresponding state observer is designed based on the identified models to estimate the acceleration signals. Experimental studies of identifying the joint models are conducted to demonstrate the proposal.

This paper presents the disturbance torque sensation techniques of control moment gyroscope (CMG) actuators. A torque sensing task without torque sensors can be done by estimating the disturbance. Two torque sensation schemes are presented and their characteristics are compared in the configuration of a disturbance observer. One scheme is based on the linear model identification by the recursive least square (RLS) method. Another sensation scheme is based on the nonlinear model identification with the sigmoidal function. Experimental studies of two torque sensation schemes for CMGs are conducted to compare the performances between two schemes along with different implementation characteristics.

In this paper, a disturbance observer is designed to sense the contact force of a human operator for a control moment gyroscope (CMG). The contact force made by a human is estimated by a disturbance. A disturbance observer is used to estimate the unknown human contact force after the system model identification by a recursive least square (RLS) method. The model-based human contact estimator is designed in a disturbance observer framework to estimate the human contact force as a disturbance. The proposed method is experimentally evaluated by comparing the accuracy of the force estimator and the measured force of a CMG.

Stabilization of the inverse model of the target system is a critical problem in a current disturbance observer (DOB) based control scheme. When the system is identified as a second order system by the recursive least square (RLS) algorithm, the minimum phase (MP) of the model is not guaranteed. This paper addresses a guaranteed minimum phase method of the identified second order model. Jury's test is conducted to check the stability. All-Pass-Filtering (APF) process are conducted for updating prior parameters of RLS to satisfy the minimum phase criteria. To verify the proposal, a single-wheel robot is identified as a second order model by the RLS method with guaranteed stability. Disturbance observer is designed based on the model. Balancing control experiments of a single-wheel robot are conducted.

This paper presents an external disturbance torque sensing technique based on a design of a disturbance observer (DOB). For the more accurate estimation of the system models, two RLS filters are formed a back-to-back cascaded structure to identify both forward and inverse models simultaneously. Monte Carlo-based recursive least squares (RLS) scheme is used for identifying the inverse model of a dynamical system by constructing DOB structure. The proposed torque sensing method is experimentally verified by estimating the external torque of a human operator on the control moment gyroscope (CMG) actuator as a disturbance.

This study confirms that botulinum neurotoxin type A (BoNT-A) decreases capsular contracture and elucidates a possible mechanism. Silicone blocks were implanted subcutaneously in 20 mice. The experimental groups received BoNT-A (1, 2·5 or 5 U) instilled into the subcutaneous pocket. After 30 days, periprosthetic capsules were harvested and evaluated. The effect of BoNT-A on the differentiation of human dermal fibroblasts to myofibroblasts in culture was examined by Western blot analysis. Changes in transforming growth factor-beta1 (TGF-β1) expression in cultured fibroblasts were determined by enzyme-linked immunosorbent assay (ELISA). In in vivo study, the thickness of capsules (P < 0·05) and the number of alpha-smooth muscle actin (α-SMA)(+) cells in capsules (P < 0·05) were significantly decreased in the experimental groups. TGF-β1 was significantly underexpressed in the experimental groups (P < 0·05). In in vitro study, BoNT-A did not significantly affect fibroblast viability. Western blot analysis showed that α-SMA protein levels were significantly decreased in the experimental groups (P < 0·05). Based on ELISA, the amount of TGF-β1 was significantly decreased in the experimental groups (P < 0·05), especially cells treated with a high dose of BoNT-A (P < 0·001). This study confirms that BoNT-A prevents capsular formation around silicone implants, possibly by blocking TGF-β1 signalling and interrupting the differentiation of fibroblasts to myofibroblasts.

TonEBP [TonE (tonicity-responsive enhancer)-binding protein] is a transcriptional activator of the Rel family like NF-κB (nuclear factor κB) and NFAT (nuclear factor of activated T-cells). TonEBP plays a key role in the protection of cells in the kidney medulla from the deleterious effects of hyperosmolality. This is achieved by enhancing expression of HSP70 (heat-shock protein 70) and other genes whose products drive cellular accumulation of organic osmolytes. TonEBP is stimulated by ambient hypertonicity via multiple pathways that regulate nuclear translocation and transactivation. In the present paper, we report that TonEBP is associated in vivo with RHA (RNA helicase A). The N- and C-termini of RHA bound the E′F loop of the DNA-binding domain of TonEBP. The interaction was not affected by DNA binding or dimerization of TonEBP. Overexpression of RHA inhibited the activity of TonEBP; however, catalytic activity of RHA was dispensable for the inhibition. When the ambient tonicity was raised, the TonEBP–RHA interaction decreased, suggesting that dissociation of RHA is a pathway to stimulate TonEBP. We conclude that the E′F loop of TonEBP interacts with RHA like NFAT and NF-κB interact with AP1 (activator protein 1) and the high-mobility group protein HMG-I(Y) respectively. While RHA interacts with and stimulates other transcription factors such as CREB (cAMP-response-element-binding protein), NF-κB and mineralocorticoid receptor, it inhibits TonEBP.

Selective absorption of isoprene from n-pentane mixtures was performed via reversible π complexation with an aqueous solution of copper(I) nitrate, which was prepared by the disproportionation reaction between copper powder and cupric nitrate trihydrate [Cu(NO3)2·3H2O] in H2O in the presence of pyridine and nitric acid as stabilizers. The absorption of isoprene by the Cu(I) solution increased with an increase in the molar ratio of isoprene/Cu(I) up to 1 and remained nearly constant thereafter. The maximum isoprene pickup achieved at the molar ratio of isoprene/Cu(I) = 1 was around 0.5 equiv of Cu(I), implying that isoprene was complexed with Cu(I) in a η2 mode. The absorption ability of the Cu(I) solution was strongly dependent on the concentrations of the stabilizers, which prevent the oxidation of Cu(I) to Cu(II). The optimal molar composition of the solution was found to be Cu(I)/pyridine/HNO3 = 1/2.7/1.

UNLABELLED Because perfluorocarbon (PFC) liquid contacts closely with the alveolar capillaries during partial liquid ventilation (PLV), PLV with cold PFC may be used for the induction of hypothermia. Twenty rabbits were randomized to PFC-induced hypothermia (PH) (n = 7; core temperature 35 degrees +/- 1 degrees C), surface hypothermia (SH) (n = 7; 35 degrees +/- 1 degrees C), or normothermia (n = 6; 39 degrees +/- 1 degrees C). We induced PH by repeated in situ exchanges of 0 degrees C perfluorodecalin during PLV. At the establishment (0 min) of hypothermia in the PH group, oxygen consumption (P = 0.04) and oxygen extraction ratio (P = 0.01) decreased from normothermic condition. Metabolic (oxygen consumption, oxygen extraction ratio, serum lactate level) and hemodynamic variables (heart rate, blood pressure, cardiac output, pulmonary artery pressure) of the PH group were not different from those of the SH group at 0, 30, 60, 90, and 120 min of hypothermia. The difference in temperature between the pulmonary artery and rectum during the hypothermic period was smaller in the PH group compared with the SH group (P = 0.033). In conclusion, hypothermia may be induced during PLV by using cold PFC. This "pulmonary method" of cooling was comparable to a systemic method of cooling with regard to a few important physiologic variables, while maintaining a narrower interorgan temperature difference. IMPLICATIONS The induction of moderate hypothermia was feasible in rabbits by administrating cold perfluorocarbon liquid into the lung. Physiologic changes induced by this pulmonary cooling were comparable to those induced by systemic cooling. Our method may be regarded as a methodological advance in the field of therapeutic hypothermia.

This study confirms that botulinum neurotoxin type A (BoNT‐A) decreases capsular contracture and elucidates a possible mechanism. Silicone blocks were implanted subcutaneously in 20 mice. The experimental groups received BoNT‐A (1, 2·5 or 5 U) instilled into the subcutaneous pocket. After 30 days, periprosthetic capsules were harvested and evaluated. The effect of BoNT‐A on the differentiation of human dermal fibroblasts to myofibroblasts in culture was examined by Western blot analysis. Changes in transforming growth factor‐beta1 (TGF‐β1) expression in cultured fibroblasts were determined by enzyme‐linked immunosorbent assay (ELISA). In in vivo study, the thickness of capsules (P < 0·05) and the number of alpha‐smooth muscle actin (α‐SMA)(+) cells in capsules (P < 0·05) were significantly decreased in the experimental groups. TGF‐β1 was significantly underexpressed in the experimental groups (P < 0·05). In in vitro study, BoNT‐A did not significantly affect fibroblast viability. Western blot analysis showed that α‐SMA protein levels were significantly decreased in the experimental groups (P < 0·05). Based on ELISA, the amount of TGF‐β1 was significantly decreased in the experimental groups (P < 0·05), especially cells treated with a high dose of BoNT‐A (P < 0·001). This study confirms that BoNT‐A prevents capsular formation around silicone implants, possibly by blocking TGF‐β1 signalling and interrupting the differentiation of fibroblasts to myofibroblasts.

We evaluated general office chair and adjustable chairs which can adjust to fit each person. We also analyzed how each design dimension was reached and affected the human body by objective EMG (Electromyogram) evaluation, and by subjective evaluation of physical discomfort and comfort. Studies like this will be very important in the database. The purpose of this study is on upgrading the physical comfortableness, eliminating users' complaints about previous chairs.

Background: In partial liquid ventilation (PLV), the nondependent lung was observed to be inflated first and the dependent lung later. The inflational time difference between the lung regions can lead to maldistribution of tidal gas and inefficient gas bubbling in the slow-inflating region during PLV. In this situation, increasing the inspiratory to expiratory (I:E) ratio of the mechanical ventilator would lessen the heterogeneity of regional ventilation and improve gas exchange possibly to a greater degree than in gas ventilation (GV). Design and setting: Animal study at the Asan Institute for Life Sciences, Seoul, Korea Subjects: Eighteen rabbits (2.6 6 0.5 kg) with acute lung injury by saline solution lavage. Interventions: Three I:E ratios were tried in GV and then in PLV. I:E ratios were changed by adjusting pause (1:2, 1:1, and 2:1; group 1) or by adjusting inspiratory flow rate (1:3, 1:1, and 2:1; group 2). Measurements and results: With increasing I:E ratio in all animals, PaO2/FIO2 increased (80 6 24, 143 6 74, and 147 6 88 mm Hg; p 5 0.001), and PaCO2 decreased (74 6 15, 66 6 16, and 66 6 15 mm Hg; p 5 0.006). The increases of PaO2/FIO2 from 1:2/1:3 to 1:1 (p 5 0.006) and from 1:1 to 2:1 (p 5 0.036) were both greater in group 1 than in group 2. PaCO2 decreased with increasing I:E ratio in group 1, but not in group 2. The change of PaO2/FIO2 by varying the I:E ratio was 49 6 65% in PLV and 14 6 14% in GV (p 5 0.003). Conclusions: Extending the I:E ratio, especially by adding pause, improved gas exchange in PLV. Oxygenation in PLV was affected by the I:E ratio to a greater degree than in GV. (CHEST 1999; 116:1032‐1038)

The pharmacokinetics of a non-narcotic analgesic, DA-5018, were compared after single intravenous (i.v.), subcutaneous (s.c.), and oral administrations, and after multiple (seven consecutive days) s.c. administration to rats. After i.v. administration of DA-5018, 1, 2, and 5 mg kg-1, the pharmacokinetic parameters of DA-5018 were independent of the dose ranges studied. After oral administration of DA-5018, absorption of the drug from gastrointestinal (GI) tract was fast, but the extent of absolute bioavailability (F) was low; the values were 23.2, 23.0, and 27.3% for 2, 5, and 10 mg kg-1, respectively. After single s.c. administration of DA-5018, absorption of the drug from the injected site was fast and the extent of absorption was fairly good; the F values were 74.5 and 71.8% for 2 and 5 mg kg-1, respectively. The lower F values after oral administration of DA-5018 to rats could be due to degradation of the drug in rat GI tract and/or considerable first-pass effect. After i.v., oral, and s.c. administration of DA-5018, the drug had a strong affinity to the rat tissues studied as reflected in the greater-than-unity tissue to plasma ratio. After i.v., oral, and s.c. administration of the drug, the biliary and urinary excretion of unchanged DA-5018 were negligible. There was no significant difference in the pharmacokinetics or tissue distribution of DA-5018 between single and multiple s.c. administration of the drug, 5 mg kg-1, to rats, indicating that there could be no tissue accumulation of the drug after multiple s.c. administration of the drug to rats.

The pharmacokinetics of M1, M2, M3, and/or M4 were compared after intravenous (iv) administration of DA-125 and/or ME2303 to mice (25 mg kg−1) and rats (5, 10, 20, 30, and 40 mg kg−1). The mean plasma concentrations of M1 were detected up to 8 h after iv administration of both DA-125 and ME2303 to mice, and were significantly higher for DA-125 than ME2303; this resulted in a considerably greater AUC (303 against 148 μg min mL−1) and a considerably slower CL of M1 (69·3 against 136 mL min−1 kg−1) after iv administration of DA-125. The MRT (371 against 189 min) and CLNR of M1 (68·7 against 136 mL min−1 kg−1) were considerably greater and slower, respectively, after iv administration of DA-125. The mean plasma concentrations of M2 were detected up to 8 and 4 h after iv administration of DA-125 and ME2303, respectively, to mice and were significantly higher for DA-125 than ME2303, resulting in a considerably greater AUC of M2 (148 against 27·1 μg min mL−1) after iv administration of DA-125. The mean plasma concentrations of M3, being the lowest among M1–M4, were detected only up to 15 min after iv administration of both DA-125 and ME2303 to mice, and were comparable after iv adminstration of DA-125 and ME2303 to mice. The mean plasma concentrations of M4 were detected up to 8 h after iv administration of both DA-125 and ME2303 to mice, and were higher after iv administration of DA-125 than ME2303, resulting in a considerably greater AUC of M4 (197 against 61·9 μg min mL−1) after iv administration of DA-125. Similar results on M1 and M2 were also obtained from rats: the mean plasma concentrations of both M1 and M2 were significantly higher after iv administration of DA-125, 10 mg kg−1, than after ME2303. The plasma concentrations of M1, M2, and M4, and hence their AUCs, were significantly higher after iv administration of DA-125, 5, 10, 20, 30, and 40 mg kg−1, to rats than after ME2303: the mean plasma concentrations of M2, approximately 0·1–0·4 μg mL−1, were maintained from 30 min to 8–10 h after iv administration of DA-125, 20, 30, and 40 mg kg−1, to rats; the plasma concentrations of M3 were the lowest among M1–M4 at all DA-125 doses; and those of M1 and M4 were maintained for a long period of time. However, after iv administration of M2, 5 mg kg−1, to rats, the mean plasma concentrations of M2 were detected up to 60 min with a mean terminal half-life of only 38·8 min, and the concentrations of M3 were negligible. After iv administration of M3, 5 mg kg−1, to rats, the mean plasma concentrations of M3 were detected up to 15 min; the plasma concentrations of M4, reaching their peak at 5 min, decayed more slowly and were higher than those of M3. The AUC of M4 after iv administration of M3, 5 mg kg−1, was comparable to that after iv administration of M4, 5 mg kg−1, to rats, suggesting that M4 is formed fast and almost completely from M3. M1 was not detected in plasma after iv administration of either M2 or M3 to rats. After iv administration of M4, 5 mg kg−1, to rats, the mean plasma concentrations of M4 decayed fast with a mean terminal half-life of 43·9 min and neither M2 nor M3 were detected in plasma. The following disposition mechanisms for M1, M2, M3, and M4 after iv administration of DA-125 to rats could be obtained from the above data: (i) the maintenance of plasma concentrations of M2 for a longer period of time after iv administration of DA-125 than those after iv administration of M2 could be due to the continuous formation of M2 from M1; (ii) the lowest plasma concentrations of M3 among M1–M4 after iv administration of DA-125 could be due to the fast and almost complete formation of M4 from M3 as soon as M3 is formed from M1, and not due to the fast renal excretion of unchanged M3; (iii) M4 was exclusively and continuously formed from M3 and the formation of M4 from M2 was negligible; and (iv) reversible metabolism among M1–M4 did not take place. The following results could also be obtained after iv administration of DA-125 or ME2303 to mice and rats: (i) the lower plasma concentrations of M1 after iv administration of ME2303 than of DA-125 could be due to the greater biliary excretion of unchanged ME2303 (approximately 30% of iv dose) than unchanged DA-125 and (ii) the lower plasma concentrations of M2 and M4 after iv administration of ME2303 than after DA-125 could be due to lower plasma concentrations of M1 and hence less formation of both M2 and M4 from M1. Liver showed the highest metabolic activity for M1 and a considerable amount of M1 was also metabolized in the kidney after 30 min incubation of 50 μg of DA-125 in 9000 g supernatant fraction of rat tissue homogenates. The mean amount of M1 remaining per gram of tissue, the total amount of M1 remaining in whole tissue, and the tissue to plasma ratio of M1 were significantly higher in the heart, lung, large intestine, and kidney at 15 min after iv administration of DA-125, 25 mg kg−1, to mice than after ME2303. M1, the active antineoplastic moiety of DA-125, had higher affinity for the lung after iv administration of DA-125 to mice than after ME2303, indicating that lung tumours could be subjected to a greater exposure to M1 after iv administration of DA-125 than ME2303. The 24 h biliary excretion of M1 was significantly greater after the iv administration of ME2303 than after DA-125 (344 against 79·3 μg). However, reversed results were obtained for M2 (267 against 467 μg). M3 and M4 were under the detection limit in the bile sample after iv administration of either DA-125 or ME2303.

The pharmacokinetics of DA-125 were compared after intravenous (i.v.) administration of the drug, 10 mg kg-1, to control male Sprague-Dawley rats (n = 9) and uranyl nitrate-induced acute renal failure (U-ARF, n = 12) rats, or male Sprague-Dawley rats fed on a 23% (control, n = 8) or a 5% (protein-calorie malnutrition, PCM, n = 9) protein diet. After i.v. administration of DA-125, almost 'constant' plasma concentrations of M1, M2, and M4 were maintained from 1-2 h to 8-10 h in all rat groups due to the continuous formation of M2 from M1 and M4 from M3. The plasma concentrations of M3 were the lowest among M1-M4 for all rat groups due to the rapid and almost complete conversion of M3 to M4 and other metabolite(s). The AUCt values of M1 (115 against 82.5 micrograms min mL-1), M2 (33.0 against 23.6 micrograms min mL-1), and M4 (26.3 against 15.1 micrograms min mL-1) were significantly higher in the U-ARF rats than in the control rats. The percentages of i.v. dose excreted in 24 h urine as M1 (under the detection limit against 0.316%), M2 (under the detection limit against 5.58%), and M4 (0.0174 against 0.719%)--expressed in terms of DA-125--were significantly lower in the U-ARF rats than in the control rats, and this could be due to the decreased kidney function in the U-ARF rats. However, the percentages of i.v. dose recovered from the GI tract at 24 h as M1 (0.0532% against under the detection limit), M3 (0.0286% against under the detection limit), and M4 (0.702% against 0.305%)--expressed in terms of DA-125--were significantly greater in the U-ARF rats than in the control rats. All U-ARF rats had ascites, but the concentrations of M1 (0.0320 micrograms mL-1), M2 (0.0265 micrograms mL-1), M3 (under the detection limit), and M4 (0.032 micrograms mL-1) in the ascites from one rat were almost negligible. The plasma concentrations and most of the pharmacokinetic parameters of M1, M2, and M4 were not significantly different between the PCM rats and their control rats.

The pharmacokinetics and tissue distribution of M1-M4 were compared after intravenous (i.v.) administration of DA-125, 25 mg kg-1, to BDF1 mice (n = 5 at each sampling time) and subcutaneously implanted Lewis-lung-carcinoma-bearing BDF1 mice (n = 10 at each sampling time. The mean plasma concentrations of M1-M4 were not significantly different between the two groups of mice, and hence similar pharmacokinetic parameters for M1-M4 were obtained. The amount of M1 in the lung was significantly greater in the tumour-bearing mice than in the control mice, resulting in a greater AUAt in the tumour-bearing mice (18,600 against 8940 micrograms min g-1), and vice versa in the liver (962 against 3840 micrograms min g-1). However, the corresponding values for other tissues were comparable between the control and tumour-bearing mice. The amount of M1 was greatest in the lung for up to 2 h in the tumour-bearing mice. M2 was the predominant metabolite among M1-M4 excreted in 24 h urine by both groups of mice; 8.36 and 10.7% of the i.v. dose were excreted in 24 h urine as M2--expressed in terms of DA-125--by the control and tumour-bearing mice, respectively. The amount of M1 in the tumour mass reached a mean Cmax of 3.75 micrograms g-1 immediately after i.v. administration of DA-125 to the tumour-bearing mice, then declined very slowly to an amount that remained almost constant for up to 24 h. This suggested that M1 has high affinity for the subcutaneously implanted Lewis lung carcinoma. The antitumour activity, such as the increase in life span (ILS) and tumour growth inhibition (TGI) of DA-125, 6-48 mg kg-1, and adriamycin (ADM), 3-18 mg kg-1, were also compared in subcutaneously implanted Lewis-lung-carcinoma-bearing BDF1 mice after four weekly i.v. administration of the drugs on days 1,8,15, and 22 following tumour implantation. More than three out of six mice survived as tumour-free for longer than 70 d at a DA-125 dose range of 6-24 mg kg-1, but there were no tumour-free mice at any dose of ADM. Assuming ILS values higher than 30% to be effective, DA-125 doses ranging from 6 to 24 mg kg-1 were effective in increasing the life span, which ADM does only within the dose range of 6-12 mg kg-1.

The pharmacokinetic parameters, tissue distribution and biliary excretion of M1-M4 were estimated after intravenous (i.v.) administration of DA-125, 2.5 mg per kg to beagle dogs. The mean values of the terminal half-life, mean residence time, total body clearance and apparent volume of distribution at steady state of M1 were 266 min, 170 min, 61.3 ml min −1 kg −1 and 9500 ml kg −1 , respectively (four male and four female dogs). M1 was highly concentrated in lung (five male and five female dogs), and this probably means that lung tumors are subjected to greater exposure to M1, an active metabolite of DA-125. The 8 h biliary excretion of M2 was significantly greater than that of M1, 53.6 vs 6860 μg (three male and two female dogs). The amount of glucuronide and/or sulfate conjugates of M1-M4 in the bile sample was negligible.

The pharmacokinetics of DA-125 or its active metabolite, M1 (FT-ADM), an adriamycin analog containing fluorine were compared after intravenous (i.v.) administration of DA-125 or M1 in rats. DA-125, 20 mg kg−1 was dissolved in 1 mM lactic acid/0.9% NaCl solution (treatment I) or 100% dimethylsulfoxide (DMSO, treatment II), and M1, 20 mgkg was dissolved in 100% DMSO (treatment III) due to its poor water solubility. The plasma concentrations of DA-125 and M1, and the pharmacokinetic parameters of DA-125, such as terminal half-life (t12, 1.64 vs 2.07 min), mean residence time (MRT, 1.52 vs 2.60 min), total body clearance (CL, 165 vs 186 ml min−1 kg−1) and apparent volume of distribution at steady state (Vdss, 254 vs 411 ml kg−1), and of M1 (based on plasma data up to 1 h), such as (t12 (30.2 vs 38.7 min), MRT (19.1 vs 31.6 min), CL (187 vs 189 ml min−1 kg−1) and Vdss(2670vs 5700 ml kg−1were similar between treatments I and II, indicating that the effect of 100% DMSO on the pharmacokinetics of DA-125 or M1 seemed to be negligible, if any. The plasma concentrations of M1, and the pharmacokinetic parameters of M1 (based on plasma data up to 8 h when the dose of M1, 20 mg kg−1 was normalized to the dose of DA-125, 20 mg kg−1), such as (t12 (255 vs 221 min), MRT (269 vs 235 min), CL (103 vs 112 ml min−1 kg−1) and Vdss (28 500 vs 26300 ml kg−1) were also similar between treatments II and III. The above results indicate that DA-125 is rapidly hydrolyzed to M1 after i.v. administration of DA-125. Therefore, the estimation of the pharmacokinetic parameters of M1 after i.v. administra- tion of DA-125 appeared not to cause any differences, if any when compared with the values after i.v. dose of M1. The rapid hydrolysis of DA-125 to M1 was demonstrated during an in vitro study; the (t12 values of hydrolysis of DA-125 were 1.97, 1.72, 0.54 and 0.54 min in the plasma from mouse, rat, dog and human, respectively, when the plasma containing DA-125 was incubated in a shaking water bath kept at 37°C and at a rate of 300 rpm.

Background and objective Inhaled corticosteroids are used to treat COPD and asthma. An association between sequence variants in the corticotrophin-releasing hormone receptor 1 (CRHR1) gene and improved lung function in asthmatics treated with inhaled corticosteroids was reported recently. This study investigated the association between the change in lung function in response to inhaled corticosteroids and single-nucleotide CRHR1 polymorphisms in patients with COPD. Methods COPD patients (n = 87) with a positive smoking history were recruited from the pulmonary clinics of 11 hospitals in Korea. Patients were treated with fluticasone propionate and salmeterol for 12 weeks and lung function was measured at baseline and after the 12-week treatment. Eighty-four of the 87 subjects were successfully genotyped. Results Seventy-one patients with the wild-type GG genotype and 13 patients with the heterozygous GT genotype in rs242 941 were evaluated. After 12-week treatment, the change in FEV(1) was significantly higher in patients with wild-type GG genotype (6.0 +/- 0.8% of predicted FEV(1)) than in GT heterozygotes (-0.8 +/- 1.8, P = 0.003). Conclusions Improved FEV(1) following inhaled corticosteroid and a long-acting beta2-agonist was associated with CRHR1 genetic polymorphism in patients with COPD.

Background and objective: A new interpretative strategy for pulmonary function tests (PFT) has been proposed by the American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force. To assess the accuracy of this strategy, clinical diagnosis was compared with the PFT interpretation in patients showing concomitant decreases in FEV1 and FVC. Methods: A retrospective study was conducted of 681 patients with normal FEV1/FVC and low FVC who underwent lung volume measurements and spirometry on the same date between July and November 2005 at Asan Medical Center, Seoul, Korea. Patients were clinically diagnosed by the consensus decision of two respiratory physicians, and the kappa coefficient was calculated to compare the clinical diagnosis with the PFT interpretation using the ATS/ERS strategy. Results: The PFT interpretation showed an obstructive pattern in 205 patients and a restrictive pattern in 476. Of the 205 patients with an obstructive pattern on PFT, 44 were clinically diagnosed with obstructive, 97 with restrictive and 17 with mixed disease, whereas 47 patients had no disease. Of the 476 patients with a restrictive pattern on PFT, 11 were clinically diagnosed with obstructive, 369 with restrictive and 60 with mixed disease, whereas 36 patients had no disease. The kappa coefficient was 0.35 (95% confidence interval: 0.26–0.44; P

OBJECTIVES Osteopontin (OPN) is a secreted glycoprotein, frequently associated with various tumors. We investigated the usefulness of plasma OPN level as a biomarker for hepatocellular carcinoma (HCC). METHODS We determined plasma levels of OPN, alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence II (PIVKA II) in a group of 62 HCC patients, in 60 patients with chronic liver diseases, and in 60 healthy control individuals using a standardized ELISA kit. To determine the source of elevated plasma level of OPN, immunohistochemical analysis of 285 HCC samples on tissue microarray was performed. RESULTS Plasma OPN levels in the HCC patients (median 954 ng/mL, range 168-5,742) were significantly higher (p-value < 0.001) than those patients with chronic liver diseases (381 ng/mL, 29-1,688) or of a healthy control group (155 ng/mL, 10-766). Within the HCC patient group, plasma OPN level increased significantly with advancing degree of Child-Pugh class and of tumor stage. Diagnostic sensitivity and specificity of OPN for HCC was 87% and 82%, respectively (cut-off value: 617.6 ng/mL). OPN had a greater area under curve value (0.898) than AFP (0.745) or PIVKA II (0.578), suggesting superior diagnostic accuracy of OPN. Immunohistochemistry of 285 samples of HCC showed that OPN was expressed in 92 of 285 tumors (32.3%). OPN expression was found in the malignant hepatocytes and cancer-infiltrating macrophages, not in the noncancerous hepatocytes or Kupffer cells. CONCLUSIONS These data propose elevated plasma OPN levels as a potential biomarker for HCC.

Alveolar hemorrhage and pulmonary edema induced by mechanical ventilation are partly dependent on cardiac output. Because cardiac output is low during hypothermia, we hypothesized that hypothermia may protect against these vascular manifestations of ventilator-induced lung injury. Twenty-seven Sprague-Dawley rats were assigned to either normothermia (37 +/- 1 degrees C)-injurious ventilation (NT; n = 10), hypothermia (27 +/- 1 degrees C)- injurious ventilation (HT; n = 10), or nonventilated control ( n = 7). The two ventilated groups were subjected to injurious ventilation of peak airway pressure 30 cm H(2)O with zero end-expiratory pressure for 20 min. Compared with the NT group, the hemorrhage/congestion score of the lung (11.2 +/- 1.5 vs. 4.7 +/- 1.6; p0.001) and the ratio of wet/dry lung weight (6.1 +/- 0.8 vs. 5.0 +/- 0.1; p = 0.046) of the HT group were lower. Compared with the NT group, protein concentration (3,471 +/- 1,985 micro g/ml vs. 1,374 +/- 726 micro g/ml; p = 0.003) and lactate dehydrogenase level (0.43 +/- 0.22 U/ml vs. 0.18 +/- 0.1 U/ml; p = 0.046) in bronchoalveolar lavage fluid of the HT group were lower. Whereas pressure-volume curve was shifted to the right in the NT group after injurious ventilation, it was not shifted in the HT group. In conclusion, hypothermia in rats attenuated the degrees of vascular manifestations and alveolar epithelial injuries induced by injurious ventilation, and preserved the mechanical properties of the lung.

Tonicity-responsive enhancer binding protein (TonEBP)- nuclear factor of activated T cell family 5 is a DNA binding protein that plays a key role in the response of cells to hypertonicity. However, TonEBP is expressed and active in tissues that are in an isotonic milieu. To explore the biological role of TonEBP, we cloned mouse TonEBP that shares 92% of amino acids with the human counterpart. TonEBP is expressed in embryonic stem cells and throughout the stages of fetal development. Immunohistochemical analysis shows expression of TonEBP in most, if not all, developing tissues, including the brain, colon, heart, muscle, and eyes. Widespread alternative splicing in exons 2–4 was detected throughout development and in different adult tissues. As a result, four different polypeptides are produced with different lengths at the NH2terminus. Two of the isoforms differ in their ability to stimulate transcription. In conclusion, the presence of TonEBP mRNA during mouse embryogenesis suggests that TonEBP functions at all stages of mouse development, as well as in isotonic adult tissues.

To devise a new form of sigh ("extended sigh") capable of providing a sufficient recruiting pressure x time, and to test it as a recruitment maneuver in patients with acute respiratory distress syndrome.Prospective uncontrolled clinical trial.Medical intensive care unit of a university-affiliated hospital.Twenty consecutive patients diagnosed with acute respiratory distress syndrome (18 men, 2 women, age 59 +/- 10 yrs).From baseline settings of tidal volume (Vt) 8 mL/kg and positive end-expiratory pressure (PEEP) 10 cm H2O on volume control mode with the high pressure limit at 40 cm H2O, the Vt-PEEP values were changed to 6-15, 4-20, and 2-25, each step being 30 secs (inflation phase). After Vt-PEEP 2-25, the mode was switched to continuous positive airway pressure of 30 cm H2O for a duration of 30 secs (pause), after which the baseline setting was resumed following the reverse sequence of inflation (deflation phase). This extended sigh was performed twice with 1 min of baseline ventilation between.Airway pressures and hemodynamic parameters were traced at each step during the extended sigh. Arterial blood gases and physiologic parameters were determined before the extended sigh (pre-extended sigh), at 5 mins after two extended sighs (post-extended sigh), and then every 15 mins for 1 hr. In our average patient, the recruiting pressure x time of the inflation phase was estimated to be 32.8-35.4 cm H2O x 90 secs. Compared with the inflation phase, inspiratory pause pressure of the deflation phase was lower at Vt-PEEP 6-15 (28.9 +/- 2.7 cm H2O vs. 27.3 +/- 2.8 cm H2O) and 4-20 (31.8 +/- 2.9 cm H2O vs. 31.1 +/- 2.9 cm H2O; both p.05). Compared with pre-extended sigh, Pao2 (81.5 +/- 15.3 mm Hg vs. 104.8 +/- 25.0 mm Hg; p.001) and static respiratory compliance both increased post-extended sigh (27.9 +/- 7.9 mL/cm H2O vs. 30.2 +/- 9.7 mL/cm H2O; p =.009). Improvement in these parameters was sustained above pre-extended sigh for the duration of the study. Major hemodynamic or respiratory complications were not noted during the study.We present a new form of sigh (i.e., extended sigh) capable of achieving an augmented recruiting pressure x time through a prolonged inflation on a gradually increased end-expiratory pressure. In view of the sustained effect and absence of major complications in our patients, extended sigh could be a useful recruitment maneuver in acute respiratory distress syndrome.

Despite increasing knowledge about partial liquid ventilation (PLV), the optimal dose of perfluorocarbon (PFC) is not yet established. Because there exist normal regions in the lung with ARDS and because PLV in the normal lung results in worsened gas exchange, we postulated that the optimal dose of PFC for PLV may be less than the functional residual capacity (FRC) dose in the lung with limited disease.Animal study at the Asan Institute for Life Sciences, Seoul, Korea.Twelve rabbits in which dependent lung-dominant lung injury was created by a modified saline solution lavage.PLV performed at six different doses of perfluorodecalin in sequence (3, 6, 9, 12, 15, and 18 mL/kg every 15 min).Our modified saline solution lavage induced atelectasis and hemorrhage confined to the dependent lung with severe hypoxia (PaO(2)/fraction of inspired oxygen = 37 +/- 6 mm Hg). Peak airway pressure (Ppeak) and inspiratory pause pressure (Ppause) with PLV were lower at doses of 3 to 15 mL/kg (all p0.05), but not different at a dose of 18 mL/kg, when compared with gas ventilation. Ppeak increased at doses of 12, 15, and 18 mL/kg, when each was compared with the preceding PFC dose. At increasing PFC doses, the change in the elastic component of airway pressure (Ppause after minus Ppause before) was negative until the dose of 9 mL/kg, but was positive at doses of 12 mL/kg and above. The change in the resistive component ([Ppeak minus Ppause] after minus [Ppeak minus Ppause] before) was negative until the dose of 6 mL/kg, but was positive at the doseor = 9 mL/kg.Respiratory mechanics during PLV for dependent lung-dominant lung injury were optimal at a PFC dose less than the FRC.