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Glutamate is the major excitatory neurotransmitter in the central nervous system, and evidence for peripheral glutamatergic fibers in mammals is still lacking. However, glutamate receptors have been identified in peripheral organs, including taste buds, myenteric plexus, and pancreatic islet cell. Protection against anoxic damage could also be explained by mechanisms mediated by postsynaptic mGluR2 or mGluR3, such as the inhibition of membrane excitability resulting from a reduction of cAMP formation by a G-protein-dependent modulation of ion channels. In addition, activation of mGluR3 present in glial cells may contribute to neuroprotection by enhancing the production of death. Thus, mGluR2/3 behaves potentially as a major defensive mechanism anoxia-tolerant species. There are a few reports for the regional pattern of hypoxic damage, which was inversely related to the expression of mGluR2/3. The aim of this study was to characterize the expression of mGluR3 in hypoxic liver in experimental model of rat liver. Proteomic analysis of protein extracts from CCl4–induced cirrhotic liver revealed the presence of the mGluR3. The presence of mGluR3 in the cirrhotic liver was confirmed by immunohistochemical analysis. There were a number of macrophages expressing mGluR3 mainly in the fibrous septa. After 2 weeks recovery, however, most of mGluR3 positive macrophages disappeared with collagen fibers. These results demonstrate that mGluR3 involved in the liver in response to persistent hypoxic status such as fibrotic/cirrhotic condition, and suggest that the expression of mGluR3 may be a key role functional metabolism and viability in the liver by interacting with the glutamate receptors in vivo.

Our objective was to investigate the effect of the uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B15 genetic polymorphism on the pharmacokinetics and pharmacodynamics of lorazepam in basal, inhibited, and induced metabolic states in healthy normal volunteers.Twenty-four healthy subjects were enrolled and grouped into UGT2B15*1/*1 or UGT2B15*2/*2 genotype groups. The pharmacokinetic and pharmacodynamic profiles of intravenous lorazepam were characterized before and after inhibition with 600 mg valproate once daily for 4 days and after induction with rifampin (INN, rifampicin) pretreatment (600 mg once daily for 10 days), with a washout period of 10 days between. The plasma concentrations of lorazepam and lorazepam glucuronide were analyzed before and at 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours after lorazepam administration by liquid chromatography-tandem mass spectrometry. Visual analog scale assessments and psychomotor coordination tests were administered before and up to 12 hours after drug administration.The UGT2B15*2/*2 group showed 0.58-fold (95% confidence interval, 0.43-0.72; P.0001) lower systemic clearance during the basal state and 1.37-fold (95% confidence interval, 1.05-1.88; P = .037) higher area under the visual analog scale-time curve during the induced state compared with the UGT2B15*1/*1 group. The mean systemic clearance of lorazepam decreased by 20% in the inhibited state and increased by 140% in the induced state. During the inhibited or induced state, absolute values of clearance were consistently lower in the *2/*2 group, but the percent changes from baseline did not differ significantly by genotype.Our results suggest that the UGT2B15*2 polymorphism is a major determinant of interindividual variability with respect to the pharmacokinetics and pharmacodynamics of lorazepam.

Pitavastatin is a potent, newly developed 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor for the treatment of hyperlipidemia. We characterized the effects of organic anion transporting polypeptide 1 B 1 (OATP 1 B 1) alleles *1a, *1b, and *15 on the pharmacokinetics of pitavastatin.Twenty-four healthy Korean volunteers who had previously participated in a pharmacokinetic study of pitavastatin (single oral dose, 1--8 mg) were further investigated. Subjects were grouped according to OATP 1 B 1 genotype. Dose-normalized area under the plasma concentration-time curve (AUC) and peak plasma concentration (C(max)) values were analyzed, because different dosages were administered to subjects, whereas the pharmacokinetics showed linear characteristics.Dose-normalized pitavastatin AUCs for *1b/*1b (group 1), *1a/*1a or *1a/*1b (group 2), and *1a/*15 or *1b/*15 (group 3) were 38.8+/-13.3, 54.4 +/-12.4, and 68.1+/-6.3 ng.h.mL(-1).mg(-1) (mean+/-SD), respectively, with significant differences between all 3 groups (P=.008) and between subjects carrying and those not carrying the *15 allele (P = .004). Dose-normalized pitavastatin C(max) values were 13.2+/- 3.3, 18.2+/-5.7, and 29.4+/- 9.6 ng.mL(-1).mg(-1) in groups 1, 2, and 3, respectively, and also showed significant differences (P=.003) in a manner similar to that shown by AUC. No significant differences were found between the genotype groups in terms of dose-normalized AUC or C(max) values of pitavastatin lactone.OATP 1 B 1 variant haplotypes were found to have a significant effect on the pharmacokinetics of pitavastatin. These results suggest that the *15 allele is associated with decreased pitavastatin uptake from blood into hepatocytes and that OATP 1 B 1 genetic polymorphisms have no effect on the pharmacokinetics of pitavastatin lactone.

There have been considerable disagreements regarding the influence of MDR1 (ABCB1) polymorphisms on the disposition of P-glycoprotein (P-gp) substrates. We speculated that the unknown function of the A allele of exon 21 G2677T/A (Ala893Ser/Thr) provides one of the reasons for the contradictory results. This study was performed to clarify the effects of major MDR1 gene polymorphisms, including a variant A allele in exon 21, on fexofenadine pharmacokinetics.We investigated the occurrence of 3 high-frequency single-nucleotide polymorphisms (SNPs) in exons 12 (C1236T), 21 (G2677T/A), and 26 (C3435T) of the MDR1 gene in 232 healthy Koreans, using a polymerase chain reaction-restriction fragment length polymorphism method, and performed haplotype analysis on these 3 SNPs. A single oral dose of 180 mg fexofenadine hydrochloride was administered to 33 healthy Korean male volunteers, who were divided into 6 groups based on the MDR1 genotype for the G2677T/A polymorphism in exon 21 and the C3435T polymorphism in exon 26.A strong linkage disequilibrium was observed among the 3 SNPs. The frequencies of the 4 major haplotypes, 1236C-2677A-3435C, C-G-C, T-G-C, and T-T-T, were 16.4%, 18.6%, 21.6%, and 32.2%, respectively. Fexofenadine disposition varied considerably among the groups. In the 2677AA/3435CC genotype group (n=3), the values of area under the concentration-time curve from time 0 to 24 hours [AUC(0-24)] were significantly lower (P=.014) than those of the other 5 genotype groups (GG/CC, GT/CT, TT/TT, GA/CC, and TA/CT). As compared with the 2677GG/3435CC subjects, the AUC(0-24) values were 17% lower in the 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects (GG/CC versus AA/CC versus TT/TT, 4017 +/- 1137 ng . h/mL versus 3315 +/- 958 ng . h/mL versus 5934 +/- 2,064 ng . h/mL; P=.018). By stratification for genotypes at position 3435, homozygous 3435TT subjects were found to have significantly higher AUC(0-24) (P=.024) and maximum plasma concentration (P=.040) values than CC subjects [AUC(0-24), 5934 +/- 2064 ng . h/mL versus 3998 +/- 1241 ng . h/mL; maximum plasma concentration, 958 +/- 408 ng/mL versus 673 +/- 242 ng/mL].The plasma concentrations of fexofenadine after a single oral administration were lower in 2677AA/3435CC subjects than in subjects with the other 5 genotype combinations of the SNPs of G2677T/A and C3435T. These findings confirm the importance of analyzing MDR1 haplotypes and provide a plausible explanation for the conflicting results regarding the effect of MDR1 polymorphisms on the disposition of P-gp substrates.

Cytochrome P450 2B6 (CYP2B6) metabolizes a number of therapeutic drugs and its metabolic activity varies markedly in human liver. Although genetic polymorphisms of CYP2B6 have been reported in noncoding and coding regions, little information is available regarding single nucleotide polymorphisms (SNPs) and their haplotypes in noncoding regions in Asians. Fourteen previously reported SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism or SNaPshot analysis in a Korean population and their haplotypes were inferred from genotype data using an expectation-maximization algorithm. The most common haplotypes were haplotype I, the reference sequence (frequency 0.35), haplotype II (0.19), haplotype III (0.19), and haplotype V (0.12), which together accounted for 85% of all haplotypes. The frequency of haplotype III, which contains -2320C, -1778G, -1186G, -750C, and 15582T, was found to be 2.4-fold higher than that of the *1J allele in Caucasians, and the frequency of haplotype V, which contains -8207C, -1456C, -750C, 516T, and 785G, was 55% of that of the *6B allele in Caucasians. Moreover, haplotype V, the *6B allele, appeared to be completely linked to -8207 within a putative nuclear receptor binding motif, suggesting that lower expressions of the *6B allele may be associated with the presence of noncoding SNPs such as -8207G>C linked to nonsynonymous SNPs. In conclusion, we found 11 previously described polymorphisms and identified four major haplotypes of CYP2B6 in Koreans. The frequencies of the *1J or *6B alleles, which may reduce CYP2B6 enzyme expression, were found to be significantly different between Koreans and Caucasians.

Our objective was to investigate the effect of the CYP3A5 genotype on the systemic clearance of midazolam in constitutive, inhibited, and induced metabolic conditions.Nineteen healthy volunteers were grouped with regard to the CYP3A5*3 allele, into homozygous wild-type (CYP3A5*1/*1, n = 6), heterozygous (CYP3A5*1/*3, n = 6), and homozygous variant-type (CYP3A5*3/*3, n = 7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days) and also after rifampin (INN, rifampicin) pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between.The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the CYP3A5*3/*3 group showed a greater decrease in systemic clearance than was seen in the CYP3A5*1/*1 group (8.5 +/- 3.8 L. h(-1). 70 kg(-1) versus 13.5 +/- 2.7 L. h(-1). 70 kg(-1), P =.027). The 1'-hydroxymidazolam-to-midazolam area under the plasma concentration-time curve ratio was also significantly lower in the CYP3A5*3/*3 group (0.58 +/- 0.35 versus 1.09 +/- 0.37 for the homozygous wild-type group, P =.026).The CYP3A5 genotype did not affect the pharmacokinetics of intravenous midazolam in the basal or induced states. However, during cytochrome P450 (CYP) 3A inhibition by itraconazole, individuals carrying the CYP3A5*1 allele were found to be less susceptible to changes in systemic clearance and showed higher 1'-hydroxymidazolam-to-midazolam area under the plasma concentration-time curve ratios, probably resulting from the relatively CYP3A4-specific inhibition caused by itraconazole.

A 10-month old male Shi-tzu was presented with a week history of scurfy skin and whitish masses located in the ventral portion of tongue. Grossly, two whitish prominences with diameters of 3 to 4 mm were found on the underside of the tongue. Microscopically, in ulcerative epidermis, deposition of dense, amorphous granular basophilic calcium salts was separated by thin fibrous connective tissue containing mild inflammation. Many fascicles were characterized by replacement of degenerating myofibers with calcification. The precise cause of calcification could not be determined; however, it is interesting that two different lesions shown in calcinosis circumscripta and slight nutritional myopathy were also observed simultaneously only in the tongue.

To evaluate the pharmacokinetic and pharmacodynamic characteristics of YH1885, a novel proton pump inhibitor, a single-blind, randomized, placebo-controlled, dose-rising, parallel-group study was conducted in 46 healthy volunteers. The volunteers were randomly allocated to single dose groups of 60 mg, 100 mg, 150 mg, 200 mg, and 300 mg (6 subjects per dose, including 2 placebos) or to multiple-dose groups of 150 mg and 300 mg (once-daily dosing for 7 days; 8 subjects per dose, including 2 placebos). The multiple-dose study was conducted separately after the single-dose study. YH1885 was administered orally after overnight fasting. Serial blood samples, urine samples, and pharmacodynamic measurements were taken. Drug concentrations in plasma and urine were determined by liquid chromatography/mass spectrometry (LC/MS). Pharmacodynamic changes were evaluated by ambulatory intragastric pH monitoring and by serial measurements of serum gastrin concentrations. Assessments of safety and tolerability also were made. Plasma concentrations of YH1885 reached peak levels 1.3 to 2.5 hours after single-dose administration and then declined monoexponentially with a terminal half-life (t(1/2)) of 2.2 to 2.4 hours in dosage groups up to 200 mg in the single-dose study. YH1885 showed linear pharmacokinetic characteristics, and little accumulation occurred after multiple administrations. The parent drug was not detected in urine. Dose-related pharmacological effects were obvious for dose groups of 150 mg and higher in the single-dose study. The mean intragastric pH and the percentage of time at pH>4 were significantly increased. The onset of drug effect was rapid, and maximal effects were observed on the first day of administration during multiple dosing. Serum gastrin levels also showed rapid increases during dosing but with a weak dose-effect relationship. Neither serious nor dose-limiting adverse effects were observed. YH1885 was found to be safe and well tolerated and effectively inhibited acid secretion with dose-dependent increases in intragastric pH. The acid-suppressing efficacy of YH1885 needs to be further evaluated in patients with gastric acid-related diseases.

Olmesartan is an angiotensin receptor blocker (ARB) and is widely used in clinical practice to treat hypertension. To compare the pharmacokinetic (PK) parameters and tolerability of two oral formulations of olmesartan (test drug: OMETAN® 20 mg tablet, reference drug: OLMETEC® 20 mg tablet) and assess their bioequivalence, a randomized, single dose, two-treatment crossover clinical study was conducted. At each period, 40 subjects received the test drug or the reference drug. Blood samples were collected at pre-dose and up to 48 h after study drug administration of each period. Plasma concentrations of olmesartan were measured using liquid chromatography-tandem mass spectrometry. To evaluate PK profiles, maximum plasma concentration (C max) and area under the concentration-time curve from zero to last measurable time (AUClast) were estimated using a noncompartmental method. Tolerability was evaluated based on the incidence of adverse events, vital signs, electrocardiograms, and laboratory tests. A total of 39 subjects completed the study. The geometric mean ratio and 90% confidence intervals (CI) of test drug to reference drug were 1.027 (0.969–1.088) for Cmax and 1.014 (0.957–1.074) for AUClast, respectively. There were no serious ad verse events and both formulations of olmesartan were well tolerated. The OMETAN 20 mg tablet was judged to be bioequivalent to the OLMETEC 20 mg tablet.

Recently, activation of macrophages, myofibroblasts and mast cells have been thought to be associated with liver fibrosis. The present study investigated the kinetics of these cells and the numeric relationship in carbon tetrachloride (CCl4)-induced rat liver cirrhosis.Macrophages and myofibroblasts were observed with immunohistochemistry and mast cells were detected by toluidine blue.Mast cells increased in proportion to the development of fibrosis with a maximum number on week 14. The numbers of macrophages and myofibroblasts increased during weeks 0 to 10 but decreased from weeks 12 to 14.The numbers of macrophages and myofibroblasts increased in the development of fibrosis but decreased when cirrhosis was induced. However, mast cells increased in both. Therefore, there was a numerical relationship among the numbers of macrophages, myofibroblasts and mast cells in liver fibrosis but none between the former two cells and the mast cells in liver cirrhosis.

The aging process is linked to changes in the physiological function of organs and changes in body composition that alter the pharmacokinetics of drugs and pharmacodynamic responses. Comorbidity and polypharmacy in the elderly decreases tolerability of drugs, leading to greater vulnerability to adverse drug reactions than that observed in younger adults. In geriatric pharmacotherapy, the general recommendation is dose reduction and slow titration, which is based on pharmacokinetic considerations and concern for adverse drug reactions, rather than clinical trial data. Older patients are under-represented in clinical trials. In the absence of evidence, extrapolation of risk–benefit ratios from younger adults to geriatric populations is not necessarily valid. Sound evidence through prospective clinical trials is essential, and geriatric societies, governments, and patient advocacy groups should collaborate to promote the inclusion of older people in clinical trials. It is believed that all involved in clinical trials have both an obligation and an opportunity to eliminate age discrimination in clinical trial practice.

OBJECTIVES It has been known that adrenal corticosteroids influence the expression of adrenomedullary catecholamine-synthetizing enzymes and also suppress the emission of axonal-like processes in cultured chromaffin cells. In the present study, it was attempted to investigate the effect of 17-alpha-estradiol on catecholamine (CA) secretion evoked by acetylcholine (ACh). DMPP. McN-A-343, excess K+ and Bay-K-8644 from the isolated perfused rat adrenal gland. METHODS Mature male Sprague-Dawley rats were anesthetized with ether. The adrenal gland was isolated by the method of WaKade. A cannula used for perfusion of the adrenal gland was inserted into the distal end of the renal vein. The adrenal gland, along with ligated blood vessels and the cannula, was carefully removed from the animal and placed on a platform of a leucite chamber. RESULTS The perfusion of 17-alpha-estradiol (1-100 uM) into an adrenal vein for 20 min produced relatively dose-dependent inhibition in CA secretion evoked by ACh (5.32 mM). DMPP (100 uM for 2 min). McN-A-343 (100 uM for 2 min) and Bay-K-8644 (10 uM for 4 min), while it did not affect the CA secretory effect of high K+ (56 mM). Also, in the presence of 17-beta-estradiol. CA secretion of ACh. DMPP and McN-A-343, without any effect on excess K(+)-evoked CA sectretion was depressed. However, in adrenal glands pre-loaded with 17-alpha-estradiol (10 uM) plus tamoxifen (2 uM), which is known to be a selective antagonist of estrogen receptors (for 20 min). CA secretory responses evoked by ACh. DMPP and McN-A-343 were condiderably recovered as compared to that of 17-alpha-estradiol only, but excess K(+)-induced CA secretion was not affected. However, pre-treatment with 17-alpha-estradiol in the presence of meclopramide (dopaminergic antagonist) did not affect the secretory effect of CA evoked by ACh. DMPP, McN-A-343 and high potassium. CONCLUSIONS These results suggest that 17-alpha-estradiol causes the marked inhibition of CA secretion evoked by cholinergic receptor stimulation, but not that by excess K+, indicating strongly that this effect may be mediated by inhibiting the influx of extracellular calcium into the rat adrenomedullary chromaffin cells through the activation of inhibitory estrogen receptors, and it also plays a modulatory role in regulating CA secretion.

Background: Voglibose is an α-glucosidase inhibitor. The purpose of this study was to evaluate the pharmacodynamic characteristics of voglibose for determining the appropriate study design and parameters for a pharmacodynamic equivalence study of voglibose. Methods: This study consisted of two studies. The single dose study had an open and single sequence design. Nineteen subjects received placebo and then one tablet of voglibose on two consecutive days with sucrose. The multiple dose study was performed with the similar design, except that it was a multiple dose of the single dose study. Nine subjects who showed an effective response in the single dose study received placebo three times and then voglibose 4 times on two consecutive days. Serial blood samples for pharmacodynamic parameters were taken until 180 mins after each administration. The baseline adjusted maximum serum glucose level (Gmax) and area under the serum glucose level-time profiles were determined and compared. Results: In the single dose study, the difference in Gmax was -10.6 ± 28.7 mg/dL. The area under the serum glucose concentration-time curve (AUGC0-1h) of placebo and voglibose were 7825.0 ± 1145.3 mg? min/dL, 7907.5 ± 917.2 mg?min/dL, respectively. In the multiple dose study, the difference in Gmax was 46.6 ± 16.1 mg/dL. The AUGC0-1h of placebo and voglibose were 8138.6 ± 721.9 mg?min/dL and 6499.7 ± 447.2 mg?min/dL, respectively. The Gmax and AUGC0-1h of the multiple dose study was significantly different between placebo and voglibose in paired t-test. Conclusion: The differences in Gmax and AUGC0-1h are suitable for pharmacodynamic parameters to evaluate bioequivalence of voglibose.

=Abstract= Pharmacokinetics, Pharmacodynamics and Safety of JES9501 after Single and Multiple Oral Administration in Healthy Subjects AnHye Kim, Bo-Hyung Kim, Dongseong Shin, Joo-Youn Cho, Kyung-Sang Yu, In-Jin Jang, Jae-Yong Chung Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea, Department of Clinical Pharmacology and Therapeutics, Kyung Hee University Hospital, Seoul, Republic of Korea , Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Korea

Purpose To compare surgical outcomes and complications after percutaneous nephrolithotomy (PCNL) under regional or general anesthesia. Materials and Methods One hundred and one patients who underwent PCNL as a first-line treatment for kidney calculi between June 2004 and June 2013 were enrolled in this retrospective study. Patients were classified into two groups by anesthetic method: 77 were allocated to the regional anesthesia group and 24 to the general anesthesia group. Patient general characteristics, stone features, surgical outcomes, and complications were compared between the two groups. Results The two groups were similar in terms of mean age and stone size, number, and type. Furthermore, they did not differ significantly in terms of general characteristics, treatment outcomes, or complications excluding postoperative fever. However, mean hospital stay was significantly shorter in the regional anesthesia group than in the general anesthesia group (8.9±3.2 days vs. 11.5±6.9 days, respectively, p=0.025). Also, the postoperative fever rate was significantly higher in the general anesthesia group (53.2% vs. 83.3%, respectively, p=0.007). Conclusions Regional anesthesia is as effective as general anesthesia during percutaneous nephrolithotomy and is associated with shorter hospital stays and lower rates of postoperative fever.

Background: Zofenopril is a new Angiotensin Converting Enzyme (ACE) inhibitor for the treatment of the patients with hypertension and congestive heart failure. This study aimed to evaluate the pharmacokinetics (PKs)/pharmacodynamics (PDs) and tolerability of zofenopril in healthy Korean subjects. Methods: A randomized, double blind, placebo-controlled, multiple dosing parallel group study with two dosage groups (zofenopril 30 mg or 60 mg) was conducted in healthy Korean male subjects. Each dosage group consisted of 10 subjects and they were randomly assigned to receive zofenopril or placebo with a ratio of 4:1. PK characteristics of zofenopril and its active metabolite, zofenoprilat, were evaluated after single or multiple dosing. Serum ACE activities and blood pressures were measured for PD evaluation. Adverse events, clinical laboratory tests, electrocardiograms, vital signs and physical examinations were performed for tolerability evaluation. Results: The PK characteristics of zofenopril and zofenoprilat after single dose and multiple doses were similar to one another. The metabolic ratio of zofenoprilat to zofenopril after single dose and multiple doses were 12.4 and 14.9, respectively, in the 30 mg dosage group, and were 6.8 and 6.6, respectively, in the 60 mg dosage group. Complete serum ACE activity inhibition was observed within 1 hour in both doses but it was maintained longer in the 60 mg dosage group compared to the 30 mg dosage group. There were no clinically significant abnormalities in tolerability evaluations.

3 Biocore Corporation, #60-21, Gasan-dong, Geumcheon-gu, Seoul, Korea Background: Olmesartan medoxomil is an angiotensin II receptor blocker commonly used in hypertension. First objective of this study was to evaluate the bioequivalence of two olmesartan formulations, Olmesartan 20 mg and 40 mg tablet (Yuhan, Pharmaceutical Corp. Seoul, Korea) as test drugs and Olmetec ® 20 mg and 40 mg tablet (Daewoong, Pharmaceutical Corp. Seoul, Korea) as reference drugs. Second objective of this study was to evaluate the dose-proportionality of two formulations. Methods: Two studies (20 mg, 40 mg) were conducted as a randomized, open-label, 2-period, crossover design. Each subject received one 20 mg or 40 mg tablet of the reference or test formulation of olmesartan medoxomil in each study. Blood samples were obtained during the 48-hour period after the dose in each treatment period. Wash-out period was 1 week in each study. Concentrations of olmesartan medoxomil in plasma were analyzed using a liquid chromatography system with tandem mass-spectrometric detection (LC/MS/MS). The primary pharmacokinetic parameters were C max (maximum concentration) and AUCt (area under the concentration-time curve from time 0 to the last sampling time). Results: A total number of 40 healthy male volunteers participated in the study and 37 volunteers completed both treatment periods in 20 mg trial. All 40 participants completed both treatment periods in 40 mg trial. The 90 % CIs for the geometric mean ratios of the pharmacokinetic parameters (test:reference drug) were 0.93 ~ 1.04 for AUC t and 0.97 ~ 1.08 for Cmax in 20 mg trial. The 90 CIs were 0.94 ~ 1.02 for AUCt and 1.00 ~ 1.11 for Cmax in 40 mg trial. All parameters of two studies satisfy the range of bioequivalence criterion. Conclusion: The obtained results indicated that pharmacokinetic exposure to Olmesartan 20 mg and 40 mg tablet was bioequivalent to that of Olmetec ® 20 mg and 40 mg tablet, respectively.

Purpose The aim of this study was to evaluate possible predictive variables for the outcome of shock wave lithotripsy (SWL) of renal stones in a single center. Materials and Methods Between March 2008 and March 2010, a retrospective review was performed of 115 patients who underwent SWL for solitary renal stones. The patients' characteristics and stone size, location, skin-to-stone distance (SSD), and Hounsfield units (HU) of stone were reviewed. The impact of the possible predictors on the disintegration of the stones was evaluated by logistic regression analysis. Receiver operator characteristic (ROC) curves were generated to compare the predictive powers of the variables. Results Seventy-nine patients (68.7%) had successful outcomes, whereas 36 patients (31.3%) had residual stones. Significant differences were found in the mean size and mean HU of the stones (size: 8.34±3.58 mm vs. 13.57±5.41 mm, p

Purpose Percutaneous nephrolithotomy (PCNL) is the procedure of choice for treating large renal stones. Pneumatic lithotripsy (Lithoclast®) is effective regardless of the stones' composition, and ultrasonic lithotripsy allows the aspiration of small debris during lithotripsy. We investigated the efficacy and safety of PCNL via Lithoclast® alone or combined with ultrasonic lithotripsy. Materials and methods Thirty-five (group A) and 39 (group B) patients underwent Lithoclast® PCNL and combination therapy, respectively, from May 2001 to March 2010, and the two groups were compared in terms of stone size, location, and composition; operative time; average number of treatments; hospital days; hemoglobin loss; ancillary procedures; rate of device failure; and initial and total stone-free rates. Results The two groups did not differ significantly in preoperative stone size, location, or composition; the average number of treatments; or the initial and overall stone-free rates. However, combination therapy was associated with a significantly lower operative time (181±50 vs. 221±65 min, respectively, p=0.004), number of hospital days (11.6±3.8 vs. 14.2±4.4 days, respectively, p=0.009), and average hemoglobin loss (1.12±0.61 vs. 1.39±1.02 g/dl, respectively, p=0.013). Transfusions were required in 6 patients (4 and 2 in each group, respectively), but there were no significant complications related to percutaneous access. There were 2 (5.7%) mechanical failures (Lithoclast® probe fracture) in the group A and 5 (12.8%) in the group B (2 cases of suction tube obstruction, 3 cases of overheating). Conclusions The combination of ultrasonic lithotripter and Lithoclast® is more effective than Lithoclast® alone because it significantly decreases operative time, hemoglobin loss, and the hospital stay. This may reflect the superior power of Lithoclast® and the ability to aspirate the debris during ultrasonic lithotripsy.

A 12-year-old female Maltese dog brought to a local veterinary clinic with two nodules in the subcutis of left shoulder. The nodules were grown gradually from 2 years ago. The nodules were removed surgically under anesthesia and examined histopathologically. They were 15×26 ㎜ in diameter (oval form) and 12×15 ㎜ in diameter (round form), respectively. Histopathologically, the lesions consisted of multilayered basaloid cells in the peripheral of the mass and ghost cells in the central region. Typical findings of these two nodules were gradually keratinized basaloid cell toward central area result in forming anuclear ghost cells. These microscopic features of cutaneous nodules were diagnosed as pilomatrixoma and the identified findings were similar to fully developed stage of human pilomatrixoma. This report may assist in the categorizing of canine pilomatrixoma using histopathological features.

Purpose: The management of pediatric trauma is substantially derived from the results of adult trauma patient. Despite the increasing of pediatric renal trauma, the management of them still remains controversial. The aim of this study is to evaluate our experience with the expectant conservative management of blunt trauma in children. Materials and Methods: We retrospectively studied 45 pediatric patients with renal trauma between 1995 and 2007. We reviewed medical records for clinical symptoms, mechanism of injury, assigned grade of renal injury, associated injuries, indication of surgery, and treatment outcomes. We graded renal injuries according to the American Association for the Surgery of Trauma Organ Injury Scale. Results: All patients of grade I, II, III, and IV were managed conservatively at beginning, if the hemodynamic state is stable. Among them, 2 patients of grade IV were done delayed operation. One patient underwent delayed renorrhaphy for persistent anemia and hypotension, and the other patient needed delayed nephrectomy because of persistent fever and worsening abdominal pain with significant urinary extravasation. All patients of grade V were undergone early nephrectomy. Conclusions: Except for persistent fever with significant extravasation and grade V injury, initial conservative management of blunt renal trauma in children is effective and recommendable at beginning, if the hemodynamic state is stable. Prospective larger randomized controlled trials will be needed. (Korean J Urol 2009;50:1125-1132) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Won Sik Ham, Won Tae Kim, Jin Sun Lee, Hee Jeong Ju, Shin Jyung Kang, Jin Hwan Oh, Youl Her, Jae Yong Chung, Kwangsung Park, Young Deuk Choi From the Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Industry Academy Cooperation Foundation, Joongbu University, Geumsan, MECOX CureMed, Seongnam, Department of Urology, Chonnam National University Medical School, Gwangju, Korea

Purpose: Penile fracture is a rare but serious urological condition. Immediate surgical repair is widely accepted as the treatment of choice in penile fracture. The aim of this study is to investigate the long-term outcome of immediate surgical treatment of penile fracture. Materials and Methods: This is a retrospective study of 12 men with penile fracture who were treated in the Department of Urology, Sanggyepaik Hospital, Seoul, Korea from January 2000 to June 2005. Diagnosis was made clinically and was confirmed by cavernosography in all our patients. All patients underwent immediate surgical repair, within two days after trauma, using a degloving incision. The long term results of the immediate surgical repair were evaluated using questionnaire on outpatient department visiting or telephoning. Results: The median patient age was 43 years (range, 18 to 57 years). The median follow-up was 32 months (range, 14 to 60 months). Of these patients, 8 (66.7%) patients were injured during sexual intercourse, whereas 4 (33.3%) patients were injured during masturbation. All patients were treated by immediate surgery. All patients reported satisfactory, painless erectile function; two developed penile curvature and one had a penile nodule. Conclusions: Immediate surgical repair of penile fracture is effective, restores erectile function, and the incidence of complications is low. (Korean J Urol 2009;50:165-168) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

For the evaluation of the kidney impairment, serum creatinine concentrations or glomerular filtration rates are mainly used, and the conditions of solitary or transplanted kidney and chronic dialysis are also taken into the considerations. Some symptoms and signs of the chronic renal disability in spite of adequate treatment add one additional grade. For evaluating bladder and urethral impairment, the criteria include voiding symptoms and signs. The patients with urinary diversions have impairment grades depending on the alteration of upper urinary tract function. For penile impairment, the degrees are evaluated using the international index of erectile function, nocturnal penile tumescence and color doppler ultrasonography. For evaluating impairment of other male reproductive organs, functional and anatomical changes of these organs, analysis of the semen or hormones and the state of solitary testis are used as the criteria. For evaluating impairment of female reproductive organs, pregnancy potential, requirement of continuous treatment and the ability of sexual intercourse are used. Also, degree of impairment is modified according to the ages in evaluating female reproductive systems. We have tried to make this evaluation system objective, scientific, and convenient, but still find it leaving much to be desired.

Purpose: There has been considerable controversy regarding the treatment of urinary incontinence (UI). The aim of our study was to investigate the efficacy and safety of the suprapubic arch (SPARC) procedure for the management of UI in elderly women. Materials and Methods: A retrospective analysis was conducted on 301 women who underwent the SPARC procedure for SUI. The patients were divided into two groups: group A (