Impact of Robotic Surgery on Residency Training for Herniorrhaphy and Cholecystectomy.

Robotic surgery has increased for common general surgery procedures. This study evaluates how robotic use affects the case distributions of herniorrhaphy and cholecystectomy for general surgery residents according to postgraduate year (PGY). We reviewed Accreditation Council for Graduate Medical Education (ACGME) biliary or hernia cases logged by surgical residents in the academic year 2017-2018. Operative reports were reviewed to compare approaches (robotic, laparoscopic, and open) by resident role and PGY level. Open cholecystectomies were excluded. Overall, 470 hernia and 657 cholecystectomy cases were logged. Hernia repairs were performed robotically in 15.9%, laparoscopically in 9.5%, and open in 74.7%. Cholecystectomies were performed robotically in 16.4% and laparoscopically in 83.6%. Residents were teaching assistants in 1.8% of hernia repairs and 1.5% of cholecystectomies. Distribution of cases by technique and PGY level was significantly different for both procedures, with chief residents performing the majority of robotic cholecystectomies (52.6%, P < .0001) and hernia repairs (59.7%, P < .0001). Migration of robotic cases to senior resident level and low percentage of teaching assistant roles held by residents suggest exposure to common operations may be delayed during general surgery residency training. Introduction of new technology in surgical training should be carefully reviewed and may benefit from a structured curriculum.

An optimized hepatocellular carcinoma prediction model for chronic hepatitis B with well-controlled viremia.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) substantially decreased in the era of potent antiviral therapy. We developed an optimized HCC risk prediction model for CHB with well-controlled viremia by nucelos(t)ide analogs (NUCs). METHOD: We analysed those who achieved virological response (VR; serum HBV-DNA < 2000 IU/mL on two consecutive assessments) by NUCs. Liver stiffness by transient elastography, ultrasonography and laboratory tests was performed at the time of confirmed VR. Patients with decompensated cirrhosis or HCC at baseline were excluded. Multivariate Cox-regression analysis was used to determine key variables to construct a novel risk-scoring model. RESULTS: Among 1511 patients, 9.5% developed HCC. Cirrhosis on ultrasonography (adjusted HR [aHR] 2.47), age (aHR 1.04), male (aHR 1.90), platelet count <135 000/uL (aHR 1.57), albumin <4.5 g/dL (aHR 1.77) and liver stiffness ≥11 kPa (aHR 6.09) were independently associated with HCC. Using these, CAMPAS model was developed with c-index of 0.874. The predicted and observed HCC probabilities were calibrated with a reliable agreement. Such results were reproduced from internal validation and external validation among the independent cohort (n = 252). The intermediate-risk (CAMPAS model score 75 ~ 161) and high-risk (score >161) groups were more likely to develop HCC compared with the low-risk group (score ≤75) with statistical significances (HRs; 4.43 and 47.693 respectively; both P < .001). CONCLUSION: CAMPAS model derived through comprehensive clinical evaluation of liver disease allowed the more delicate HCC prediction for CHB patients with well-controlled viremia by NUCs.

Immersive Experience Model of the Elderly Welfare Centers Supporting Successful Aging.

This study investigates the application of immersive experience services to leisure facilities for the successful aging of the elderly. In the past, the social image of the elderly was that of passive beings who needed care due to physical and cognitive decline associated with biological aging. However, the concept of "successful aging" actively highlighting the positive aspects of aging and trying to promote longer and healthier life has started to acquire importance in recent years. In this context, elderly welfare centers can be described as facilities that encourage learning, leisure, and social activities of the elderly with impaired physical and cognitive functions. The use of recent immersive experience technologies such as virtual reality and mixed reality (MR), in order to mitigate physical and spatial constraints and provide an immersion into the desired environment and situation, could contribute substantially to the health of the elderly. However, the application of immersive technologies is concentrated on the provision of entertainment, education, and medical facilities. The number of previous studies on the immersion experiences of the elderly is limited, and the connection between immersion experiences and various services and programs that promote successful aging at elderly welfare centers requires further research. This study analyzes the function and space of the elderly welfare centers for successful aging through the review of previous studies and classifies immersion technology categories based on the review of the relevant literature. The study analyzes the health benefits of immersive experience technologies and related products and services and proposes an immersive experience service model for the elderly welfare center. The results of the study could provide a valuable input for the spatial application of immersive experience technologies for successful aging in the future.

Perspective Insights of Exosomes in Neurodegenerative Diseases: A Critical Appraisal.

Exosomes are small membranous entities of endocytic origin. Their production by a wide variety of cells in eukaryotes implicates their roles in the execution of essential processes, especially cellular communication. Exosomes are secreted under both physiological and pathophysiological conditions, and their actions on neighboring and distant cells lead to the modulations of cellular behaviors. They also assist in the delivery of disease causing entities, such as prions, α-syn, and tau, and thus, facilitate spread to non-effected regions and accelerate the progressions of neurodegenerative diseases. The characterization of exosomes, provides information on aberrant processes, and thus, exosome analysis has many clinical applications. Because they are associated with the transport of different cellular entities across the blood-brain barrier (BBB), exosomes might be useful for delivering drugs and other therapeutic molecules to brain. Herein, we review roles played by exosomes in different neurodegenerative diseases, and the possibilities of using them as diagnostic biomarkers of disease progression, drug delivery vehicles and in gene therapy.

Acute HIV-1 infection presenting with fulminant encephalopathy.

Human immunodeficiency virus (HIV)-1 directly affects the nervous system, causes distinct neurological symptoms, and indirectly results in opportunistic infections, which include herpes virus simplex (HSV)-1, HSV-2, varicella zoster virus, and cytomegalovirus encephalitis caused by immunodeficiency. Early HIV-1 invasion of the central nervous system is also possible, and acute encephalopathy is a potentially lethal complication. We encountered a case of fulminant encephalopathy as a primary presentation of acute HIV-1 infection, in which highly active antiretroviral treatment resulted in a full clinical recovery. This case highlights the importance of considering acute HIV-1 infection in the differential diagnosis of reversible encephalopathy.

Phosphorylation on TRPV4 Serine 824 Regulates Interaction with STIM1.

The TRPV4 cation channel, a member of the TRP vanilloid subfamily, is expressed in a broad range of tissues where it participates in the generation of a Ca2+ signal and/or depolarization of membrane potential. Here, we identified stromal interaction molecule 1 precursor (STIM1) as an auxiliary protein of this epithelial Ca2+channel using confocal microscopy analysis and GST pull-down assay. The STIM1 protein associates specifically with the C-terminal tail of TRPV4 to form a complex. In previous reports, we demonstrated that the serine824 residue of TRPV4 is one of the target phosphorylation sites of serum/glucocorticoid regulated kinase 1 (SGK1). In this report we further identified the role of serine 824 phosphorylation. The TRPV4 mutant S824D (not S824A) exhibited a diminished capacity to bind STIM1. Using GST pull-down and co-immunoprecipitation assays, we demonstrated that STIM1 is part of the TRPV4 protein complex. Our observations clearly suggest that the formation of a complex between TRPV4 and STIM1 and its plasma membrane localization are regulated through phosphorylation of serine824 of TRPV4, and that the STIM1-TRPV4 complex plays crucial roles in routing TRPV4 to the plasma membrane from the endoplasmic reticulum and in maintaining its function.

Differential diagnosis between tuberculous spondylodiscitis and pyogenic spontaneous spondylodiscitis: a multicenter descriptive and comparative study.

BACKGROUND CONTEXT: Although tuberculous and pyogenic spondylodiscitis are common causes of spinal infections, their protean manifestation complicates differential diagnosis. PURPOSE: The clinical, laboratory, and radiologic characteristics of tuberculous and pyogenic spontaneous spondylodiscitis were compared in this study. STUDY DESIGN: This multicenter retrospective study was conducted in 11 teaching hospitals in the Republic of Korea from January 2011 to December 2013. PATIENT SAMPLE: Study subjects included adult patients (≥18 years) diagnosed with tuberculous (n=60) or pyogenic (n=117) spontaneous spondylodiscitis. OUTCOME MEASURES: Risk factors for tuberculous spondylodiscitis were determined, and their predictive performance was evaluated. METHODS: Multivariate logistic regression analysis was performed to determine predictors independently associated with tuberculous spondylodiscitis. Receiver-operating characteristic curve analysis using the presence or absence of risk factors was used to generate a risk index to identify patients with increased probability of tuberculous spondylodiscitis. RESULTS: Of 177 patients, multivariate logistic regression analysis showed that patients with tuberculous spondylodiscitis (n=60) were more frequently women, with increased nonlumbar spinal involvement and associated non-spinal lesions, delayed diagnosis, higher serum albumin levels, reduced white blood cell counts, and lower C-reactive protein and procalcitonin levels. Among 117 patients with pyogenic spondylodiscitis, the most frequent causative microorganism was Staphylococcus aureus (64.1%). The mean diagnostic delay was significantly shorter, which may reflect higher clinical expression leading to earlier diagnosis. A combination of clinical data and biomarkers had better predictive value for differential diagnosis compared with biomarkers alone, with an area under the curve of 0.93, and sensitivity, specificity, and positive and negative predictive values of 95.0%, 79.5%, 70.4%, and 96.9%, respectively. CONCLUSIONS: This study provides guidance for clinicians to predict the causative organisms of spondylodiscitis in uncertain situations and before culture or pathologic examinations. Clinical data and single biomarkers combined can be useful for differential diagnoses between tuberculous and pyogenic spondylodiscitis.

Genome-wide analysis of HOXC9-induced neuronal differentiation of neuroblastoma cells.

Induction of differentiation is a therapeutic strategy in neuroblastoma, a common pediatric cancer of the sympathetic nervous system. The homeobox protein HOXC9 is a key regulator of neuroblastoma differentiation. To gain a molecular understanding of the function of HOXC9 in promoting differentiation of neuroblastoma cells, we conducted a genome-wide analysis of the HOXC9-induced differentiation program by microarray gene expression profiling and chromatin immunoprecipitation in combination with massively parallel sequencing (ChIP-seq). Here we describe in details the experimental system, methods, and quality control for the generation of the microarray and ChIP-seq data associated with our recent publication [1].

Automated multidimensional image analysis reveals a role for Abl in embryonic wound repair.

The embryonic epidermis displays a remarkable ability to repair wounds rapidly. Embryonic wound repair is driven by the evolutionary conserved redistribution of cytoskeletal and junctional proteins around the wound. Drosophila has emerged as a model to screen for factors implicated in wound closure. However, genetic screens have been limited by the use of manual analysis methods. We introduce MEDUSA, a novel image-analysis tool for the automated quantification of multicellular and molecular dynamics from time-lapse confocal microscopy data. We validate MEDUSA by quantifying wound closure in Drosophila embryos, and we show that the results of our automated analysis are comparable to analysis by manual delineation and tracking of the wounds, while significantly reducing the processing time. We demonstrate that MEDUSA can also be applied to the investigation of cellular behaviors in three and four dimensions. Using MEDUSA, we find that the conserved nonreceptor tyrosine kinase Abelson (Abl) contributes to rapid embryonic wound closure. We demonstrate that Abl plays a role in the organization of filamentous actin and the redistribution of the junctional protein ß-catenin at the wound margin during embryonic wound repair. Finally, we discuss different models for the role of Abl in the regulation of actin architecture and adhesion dynamics at the wound margin.

Global diversification at the harsh sea-land interface: mitochondrial phylogeny of the supralittoral isopod genus Tylos (Tylidae, Oniscidea).

The supralittoral environment, at the transition between sea and land, is characterized by harsh conditions for life. Nonetheless, evolution of terrestrial isopods (Oniscidea), the only group of Crustacea fully adapted to live on land, appears to have involved a transitional step within the supralittoral. The two most basal oniscidean lineages (Ligiidae and Tylidae) have representatives that successfully colonized the supralittoral. One of them is the genus Tylos, which is found exclusively in supralittoral sandy beaches from tropical and subtropical coasts around the world. Comprehensive phylogenetic hypotheses for this genus are lacking, which are necessary for understanding the evolution and biogeography of a lineage that successfully diversified in the harsh sea-land interface. Herein, we studied the phylogenetic relationships among 17 of the 21 currently recognized species of the genus Tylos, based on sequences from four mitochondrial genes (Cytochrome Oxidase I, Cytochrome b, 16S rDNA, and 12S rDNA). Maximum Likelihood and Bayesian phylogenetic analyses identified several lineages with deep divergences and discrete geographic distributions. Phylogenetic and distributional patterns of Tylos provide important clues on the biogeography and evolution of this group. Large divergences among the most basal clades are consistent with ancient splits. Due to the biological characteristics of Tylos, which likely prevent dispersal of these isopods across vast oceanic scales, we argue that tectonic events rather than trans-oceanic dispersal explain the distribution of Tylos in different continents. Overwater dispersal, however, likely enabled range expansions within some basins, and explains the colonization of volcanic oceanic islands. Present-day distributions were also likely influenced by sea level and climate changes. High levels of allopatric cryptic genetic differentiation are observed in different regions of the world, implying that the dispersal abilities of Tylos isopods are more limited than previously thought. Our results indicate that a taxonomic revision of this group is necessary.

HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation.

BACKGROUND: Cellular differentiation is characterized by the acquisition of specialized structures and functions, cell cycle exit, and global attenuation of the DNA damage response. It is largely unknown how these diverse cellular events are coordinated at the molecular level during differentiation. We addressed this question in a model system of neuroblastoma cell differentiation induced by HOXC9. RESULTS: We conducted a genome-wide analysis of the HOXC9-induced neuronal differentiation program. Microarray gene expression profiling revealed that HOXC9-induced differentiation was associated with transcriptional regulation of 2,370 genes, characterized by global upregulation of neuronal genes and downregulation of cell cycle and DNA repair genes. Remarkably, genome-wide mapping by ChIP-seq demonstrated that HOXC9 bound to 40% of these genes, including a large number of genes involved in neuronal differentiation, cell cycle progression and the DNA damage response. Moreover, we showed that HOXC9 interacted with the transcriptional repressor E2F6 and recruited it to the promoters of cell cycle genes for repressing their expression. CONCLUSIONS: Our results demonstrate that HOXC9 coordinates diverse cellular processes associated with differentiation by directly activating and repressing the transcription of distinct sets of genes.

Luteolin suppresses UVB-induced photoageing by targeting JNK1 and p90 RSK2.

Multiple lines of evidence suggest that natural compounds can prevent skin ageing induced by ultraviolet light. Luteolin, a bioactive compound found in chilli, onion, broccoli, celery and carrot, has been reported to exhibit anti-photoageing effects in vitro. However, the molecular targets and mechanisms of luteolin are still poorly understood. In this study, we sought to investigate the effects of luteolin on UVB-induced photoageing and the molecular mechanisms involved, using HaCaT human keratinocytes and SKH-1 hairless mice. Luteolin was found to inhibit UVB-induced MMP-1 expression in HaCaT cells, as well as UVB-induced activation of AP-1, a well-known transcription factor targeting the MMP-1 promoter region, as well as c-Fos and c-Jun, which comprise the AP-1 complex. In contrast, Western blot data showed that UVB-induced phosphorylation of JNK, ERK and p90RSK was not inhibited by luteolin. In vitro kinase assay data revealed that luteolin significantly suppressed JNK1 and p90RSK activity, but not that of JNK2 and ERK2. Pull-down assays showed that luteolin binds JNK1 in an ATP-competitive manner and p90RSK2 in an ATP-independent manner. Luteolin also inhibited UVB-induced wrinkle formation and MMP-13 expression, a rodent interstitial collagenase in mouse skin, in vivo. Taken together, our observations suggest that luteolin exhibits anti-photoageing effects in vitro and in vivo and may have potential as a treatment for the prevention of skin ageing.

Changes in flavor precursors, pungency, and sugar content in short-day onion bulbs during 5-month storage at various temperatures or in controlled atmosphere.

Short-day onion bulbs (cv. TG 1015Y) were stored in 1% O(2,) 99% N(2) air at 5 °C (controlled atmosphere [CA]), or in ambient air at 5, 24, or 30 °C, for 5 mo. Changes in flavor precursors, pungency, and sugar content were investigated. After 5 mo of storage, 1-propenyl-L-cysteine sulfoxide concentrations increased continuously at 5 °C, gradually decreased in CA, slightly increased for 3 mo, and returned to initial levels at 24 °C and decreased below initial levels at 34 °C. Methyl-L-cysteine sulfoxide concentrations remained unchanged in all storage conditions. Onion pungency levels significantly increased at 5 °C, and decreased at 30 °C. Storage in CA and at 24 °C resulted in some fluctuations in pungency but the levels remained similar to initial levels. The calculated pyruvic acid concentrations were approximately 1.0 µmole/mL higher than the measured concentrations, and showed an increase at 5 °C and a slight reduction at 30 °C, consistent with the pungency results. Storage at 5 °C and in CA resulted in slight increases in fructose and glucose concentrations for 3 to 4 mo with subsequent rapid decreases, while sucrose concentrations remained unchanged. However, at 24 and 30 °C, fructose and glucose concentrations continuously decreased, accompanied by a continuous increase in sucrose concentrations. Storage in CA maintained the quality of onions best, as evidenced by the smallest changes in flavor precursors, pungency, and sugar concentrations, while storage at 5 °C resulted in increased pungency. Storage at 24 and 30 °C was tested for the purpose of comparison only; these temperatures are not recommended for commercial storage.

Increased expression of SLC2A9 decreases urate excretion from the kidney.

Urate is the final metabolite of purine in humans. Renal urate handling is clinically important because under-reabsorption or underexcretion causes hypouricemia or hyperuricemia, respectively. We have identified a urate-anion exchanger, URAT1, localized at the apical side and a voltage-driven urate efflux transporter, URATv1, expressed at the basolateral side of the renal proximal tubules. URAT1 and URATv1 are vital to renal urate reabsorption because the experimental data have illustrated that functional loss of these transporter proteins affords hypouricemia. While mutations affording enhanced function via these transporter proteins on urate handling is unknown, we have constructed kidney-specific transgenic (Tg) mice for URAT1 or URATv1 to investigate this problem. In our study, each transgene was under the control of the mouse URAT1 promoter so that transgene expression was directed to the kidney. Plasma urate concentrations in URAT1 and URATv1 Tg mice were not significantly different from that in wild-type (WT) mice. Urate excretion in URAT1 Tg mice was similar to that in WT mice, while URATv1 Tg mice excreted more urate compared with WT. Our results suggest that hyperfunctioning URATv1 in the kidney can lead to increased urate reabsorption and may contribute to the development of hyperuricemia.

An assessment of the utility of universal and specific genetic markers for opium poppy identification.

The proper identification of illicit plants such as Papaver somniferum L (opium poppy) is important for law enforcement agencies. The identification of opium poppy was presently tested using 10 genetic markers that are universal for all plants or specific to a few poppy plants. The genetic distances of universal markers such as nuclear internal transcribed spacer (ITS), 18S rRNA, plastid rbcL, and trnL-trnF intergenic spacer (IGS) of 14 species included in the Papaveraceae and Fumariaceae family were acquired by sequence comparisons. Both the ITS region and trnL-trnF IGS showed high levels of interspecific divergence. Six Papaver genera-specific markers were developed from coding regions involved in morphine biosynthesis. Three markers (TYDC, NCS, and BBE) produced amplicons only in opium poppy, providing a presence/absence test for opium poppy, while three additional markers (CYP80B1, SAT, and COR) were genus specific. These 10 markers might be useful for the forensic DNA analysis of opium poppy.

Association between low bone mass and aortic valve sclerosis in Koreans.

BACKGROUND: Osteoporosis or low bone mass has been associated with cardiovascular disease and calcification in several clinical studies. However, few studies have assessed the relationship between bone mass and valvular calcification. The aim of this study was to evaluate the relationship between low bone mass and aortic valve sclerosis in Korean men and women. METHODS: A total of 211 men and 117 women were included in this study. Each subject's bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry, and aortic valve sclerosis was assessed using transthoracic echocardiography. Association between low bone mass and aortic valve sclerosis was assessed with multivariate logistic regression analysis in this cross-sectional study. RESULTS: Of 328 total subjects enrolled in this study, 50 men (23.7%) and 18 women (15.4%) were found to have aortic valve sclerosis. The mean (+/-SD) BMD T-scores were -0.5 (+/-0.8) in men and -0.9 (+/-1.0) in women. After adjusting for covariates, only women with aortic valve sclerosis had significantly lower BMD T-scores than those without it. Multivariate logistic regression analysis showed that age, smoking and hypertension were independently associated with increased risk of aortic valve sclerosis in men. In women, however, logistic regression analysis showed that BMD T-score, as well as age, was an independent variable for aortic valve sclerosis. We also found that a T-score of less than -1.5 was significantly associated with increased risk of aortic valve sclerosis in women compared to normal T-scores. CONCLUSION: Low bone mass might be independently associated with increased risk of aortic valve sclerosis in women, but not in men. Women with low bone mass should be further evaluated for the presence of aortic valve sclerosis and related cardiovascular diseases.

RNA interference of long-chain acyl-CoA synthetase 6 suppresses the neurite outgrowth of mouse neuroblastoma NB41A3 cells.

Lipogenesis is crucial during neuronal development. Abnormal lipid metabolism causes neurological disorders such as Refsum disease and contributes to tumor formation. Long-chain acyl-CoA synthetase (Acsl) ligates coenzyme A to fatty acids, thereby activating the lipid metabolism pathway. Here, we designed a specific small interference RNA (siRNA) against mouse Acsl6, pU6-487i and pU6-586i, and investigated the function of Acsl6 in neuron differentiation. Expression of mAcsl6 mRNA and protein was markedly decreased by pU6-487i and pU6-586i in NB41A3 mouse neuroblastoma cells. We established two stable cell lines, NB41A3-487 and NB41A3-586, which expressed mAcsl6 siRNA. Knockdown of the mAcsl6 gene inhibited the proliferation of NB41A3 cells; in NB41A3-586 cells neurite outgrowth was suppressed, while in NB41A3-487 cells it was almost absent. In addition, pU6-487i was more effective than pU6-586i in the reduction of cell proliferation and neurite outgrowth. The decline noted in the growth curves as well as the neurite outgrowth resulting from mAcsl6 knockdown indicate that the mAcsl6 gene plays a pivotal role in neuron development.

Preimplantation and fetal development of mouse embryos cultured in a protein-free, chemically defined medium.

Mouse two-cell embryos of block (ICR) or nonblock (F1 of C57BL x DBA) strains were cultured in modified Chatot, Ziomek, and Bavister medium, supplemented with bovine serum albumin or polyvinyl alcohol, a synthetic macromolecule. The supplementation did not influence morula compaction and blastocyst formation, mean cell numbers of total blastomeres, inner cell mass (ICM) cells and trophectodermal (TE) cells in blastocysts, rates of pregnancy and delivery, mean litter size, number of implantation spots in pregnant females, and the expression of several genes related to pluripotency, organogenesis, and implantation.

Gene therapy of uterine leiomyomas: adenovirus-mediated expression of dominant negative estrogen receptor inhibits tumor growth in nude mice.

BACKGROUND: Leiomyomas (fibroids) are common estrogen-dependent uterine tumors with no effective medicinal treatment; hysterectomy is the mainstay of management. STUDY DESIGN: This study was undertaken to investigate a potential therapy for leiomyoma; we used a mutated dominant-negative estrogen receptor gene delivered via an adenoviral vector (Ad-ER-DN). RESULTS: Ad-ER-DN transduction, in both human and rat leiomyoma cell lines, induced an increase in both caspase-3 levels and BAX/Bcl-2 ratio with evident apoptosis in the TdT-mediated dUTP nick-end labeling assay. In nude mice, rat leiomyoma cells ex vivo transduced with Ad-ER-DN supported significantly smaller tumors compared with Ad-LacZ-treated cells 5 weeks after implantation. In mice treated by direct intratumor injection into preexisting lesions, Ad-ER-DN caused immediate overall arrest of tumor growth. The Ad-ER-DN-treated tumors demonstrated severely inhibited cell proliferation (BrdU index) and a marked increase in the number of apoptotic cells (TdT-mediated dUTP nick-end labeling index). CONCLUSION: Dominant-negative estrogen receptor gene therapy may provide a nonsurgical treatment option for women with symptomatic uterine fibroids who want to preserve their uteri.

Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of 2-(allylthio) pyrazine, a chemoprotective agent, in rats: the role of CYP3A23 induction.

It has been reported that the total body clearance (CL) of 2-(allylthio)pyrazine (2-AP) was significantly faster after intravenous administration of 2-AP to rats pretreated with 3-methylcholanthrene, phenobarbital, and dexamethasone (main inducers of CYP1A1/2, CYP2B1/2, and CYP3A1/2, respectively, in rats) than those in respective control rats. It has also been reported that expression of CYP2E1 and CYP3A1(23) increased 2.3 and 4 times, respectively, in rats with acute renal failure induced by uranyl nitrate (U-ARF) compared with those in control rats. However, CYP1A2 and CYP2B1/2 expression was not changed. Therefore, it could be expected that the pharmacokinetics of 2-AP could be changed in rats with U-ARF due to increase in expression of CYP3A23 in the rats. After intravenous administration of 2-AP at a dose of 50 mg/kg to rats with U-ARF, the area under the plasma concentration-time curve from time zero to time infinity of 2-AP was significantly smaller (1030 versus 1360 microg min/ml) due to significantly faster CL of 2-AP (48.4 versus 36.8 ml/min/kg). This could be due to increased expression of CYP3A23 in rats with U-ARF.