Pharmacokinetics and pharmacodynamics of FSK0808 and Gran after single intravenous drip administration or single subcutaneous administration: comparative study in healthy Japanese adult male subjects.

FSK0808 is a recombinant human granulocyte colony-stimulating factor developed by Fuji Pharma Co., Ltd and Mochida Pharmaceutical Co., Ltd. as a biosimilar product of Gran®. We verified the pharmacokinetic/pharmacodynamic equivalence of FSK0808 and commercially available Gran® by a randomized crossover study of single intravenous dose (200 µg/m(2)) and single subcutaneous dose (400 µg/m(2)) in healthy Japanese adult male subjects. According to the bioequivalence guidelines, the area under the blood concentration - time curve by 48 hours after administration (AUC0-48) in a single intravenous drip (IVD) study, and AUC0-48 and maximum blood concentration (Cmax) in a single subcutaneous (SC) dose study were used as primary endpoints, and the pharmacodynamic parameters including absolute neutrophil count (ANC) or number of CD34 positive cells (CD34(+) cells) as secondary endpoints. The safety was evaluated based on the characteristics and incidence of adverse reactions. As a result, the 90% confidence interval (CI) of the difference in mean value for AUC0-48 among drugs ranged from log(0.8) to log(1.25), in the IVD study, and those for Cmax and AUC0-48 were within the range of log(0.8)-log(1.25) in the SC study. Those for secondary endpoints were all within the range of log(0.8)-log(1.25). Thus, the pharmacokinetics/pharmacodynamics of both drugs were considered equivalent for all routes of administration, and the profiles of adverse reactions were also very similar.

Draft genome sequence and morphological data of Planifilum fimeticola PLACP1, a thermophilic chloramphenicol-resistant bacterium isolated from thermophilic sludge.

Planifilum is a thermophilic aerobic Actinomyces often found in compost that is suggested to play a primary role in the degradation of organic matter and is a potential antibiotic-resistance gene (ARG)-hosting bacterium during the composting process. Planifilum fimeticola PLACP1 was isolated from thermophilic sludge on a Columbia plate supplemented with chloramphenicol. PLACP1 was Gram-stain-positive with cells longer than 20 µm that branched and intertwined with each other. A draft genome sequence of P. fimeticola PLACP1 was generated using the Illumina NovaSeq system and deposited in the National Center for Biotechnology Information database under the BioProject accession numbers PRJDB17484 and SAMD00736731. The genome sequence comprised 3,395,140 bp, with 57.97 % GC content and 3,368 genes, including 3,267 protein-coding, 6 rRNA, and 56 tRNA genes. Based on the Comprehensive Antibiotic Resistance Database, 237 predicted gene products were related to ARGs, including 44 macrolide antibiotic-related genes (19 %) as the largest group. This dataset will be beneficial for the morphological identification, comparative genomic analyses, and ARG research in the genus Planifilum.

Genetic polymorphisms of enzymes related to oral tegafur/uracil therapeutic efficacy in patients with hepatocellular carcinoma.

Oral tegafur/uracil therapy has been indicated for patients with hepatocellular carcinoma (HCC) and is often used as a single-agent treatment. However, how the treatment efficacy is related to 5-fluorouracil (5-FU) metabolic enzymes is unclear. We investigated genetic polymorphisms of the 5-FU metabolic enzymes in Japanese patients with HCC. We examined two genetic polymorphisms of the metabolic enzymes cytochrome P450 2A6 (CYP2A6) and dihydropyrimidine dehydrogenase (DPD) in 58 Japanese hepatitis C virus-seropositive HCC patients. To measure efficacy, we investigated genetic polymorphisms of the variable number of tandem repeats (VNTRs) of thymidylate synthase (TS) and classified the genotypes as high or low expression types. The frequency of the CYP2A6*4 allele (no-activity allele) among 58 HCC patients was 0.233 and a homozygous genotype (*4/*4) was found in five patients. The heterozygous genotype (T/C) of DPYD*9 (T85C) was detected in eight patients and the frequency of the DPYD*9 allele among 58 HCC patients was 0.069. Of 58 patients, 42 were classified as high expression type and 16 as low expression type for TS VNTR. Fifteen of these 16 patients appeared to have normal CYP2A6 metabolic activity and 13 of these 15 patients likely had normal DPD metabolic activity. Only 13 of 58 HCC patients (22.4%) tested may respond positively to treatment with oral tegafur/uracil. Therefore, when administering oral 5-FU in patients with HCC, it is important to consider three genetic polymorphisms (CYP2A6, DPYD, and TS) associated with 5-FU metabolic enzymes.

[Clinical verification of serum procalcitonin measurement in sepsis].

To evaluate the clinical application of measuring procalcitonin (PCT) level for diagnosis of bacterial sepsis in patients with and without systemic inflammatory response syndrome(SIRS), we studied the relationship between blood culture (BC) and serum PCT level in clinical 207 cases. In addition, we evaluated the time courses of PCT and other inflammatory markers: tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), E-selectin, WBC count and C-reactive protein (CRP) in 5 bacterial septic patients with SIRS. Serum PCT showed sensitivity of 41% and specificity of 61%, while BC showed specificity of 88%. In 27 BC-positive cases, serum PCT was significantly elevated in gram-negative bacterial sepsis. We observed 11 cases with BC(+) and serum PCT below 0.5 ng/ml. Major causes of these discrepancies were probably due to gram-positive bacterial infection, local bacterial infection or pretreatment with broad-spectrum antibiotics. In contrast, 10 cases with BC(-) and serum PCT over 10 ng/ml were presumably due to some cytokine elevation caused by virus infection or collagen diseases. In 5 cases studied for inflammatory markers, TNF-alpha level elevated earlier than the others and followed by PCT, IL-6, WBC, CRP, and E-selectin. It was suggested that the measurement of serum procalcitonin in septic patients is clinically useful marker to diagnose gram-negative bacterial septic patients with SIRS.

[Molecular epidemiology of Panton-Valentine leukocidin (PVL) -positive Staphylococcus aureus associated with skin and soft tissue infection].

Panton-Valentine leukocidin (PVL) secreted by Staphylococcus aureus is known to cause severe skin, soft tissue and lung infections. To assess the prevalence and genetic characteristics of PVL-positive S. aureus in our hospital, we investigated 86 S. aureus isolates isolated from skin and soft tissue pus between September 2011 and May 2012 at Daisan Hospital, the Jikei University School of Medicine (Tokyo, Japan). All isolates were investigated for the mecA gene and PVL gene by PCR amplification. The MRSA isolates confirmed were genotyped using SCCmec typing. PVL-gene positive isolates confirmed by the PVL-RPLA (reverse passive latex agglutination) assay were characterized by agr typing and multilocus sequence typing (MLST). Overall 6 (3 MSSA isolates and 3 MRSA isolates) PVL-positive strains (7.0%) were detected. The PVL prevalence was 11.1% in MRSA and 5.1% in MSSA. PVL-positive strains were isolated from young adults (range: 8-47 years) outpatient. Patients infected with PVL-positive MRSA were significantly younger than those infected with PVL-negative MRSA(32 and 68 years, respectively; P = 0.009, t-test). The 6 PVL positive strains were assigned by the MLST to 6 STs that were prevalent among PVL-positive strains. The SCCmec type of the PVL-positive MRSA were classified into 2 types (type IV or V) that were generally characteristic of CA-MRSA. Our data are consistent with some previous reports showing that PVL gene is found in certain ST strains. The PVL-positive strain must be taken into account when S. aureus is isolated from young adult SSTI.

Identification of Capsular Polysaccharide Synthesis Loci Determining Bacteriophage Susceptibility in Tetragenococcus halophilus.

Bacteriophages infecting Tetragenococcus halophilus, a halophilic lactic acid bacterium, have been a major industrial concern due to their detrimental effects on the quality of food products. Previously characterized tetragenococcal phages displayed narrow host ranges, but there is little information on these mechanisms. Here, we revealed the host's determinant factors for phage susceptibility using two virulent phages, phiYA5_2 and phiYG2_4, that infect T. halophilus YA5 and YG2, respectively. Phage-resistant derivatives were obtained from these host strains, and mutations were found at the capsular polysaccharide (CPS) synthesis (cps) loci. Quantification analysis verified that capsular polysaccharide production by the cps derivatives from YG2 was impaired. Transmission electron microscopy observation confirmed the presence of filamentous structures outside the cell walls of YG2 and their absence in the cps derivatives of YG2. Phage adsorption assays revealed that phiYG2_4 adsorbed to YG2 but not its cps derivatives, which suggests that the capsular polysaccharide of YG2 is the specific receptor for phiYG2_4. Interestingly, phiYA5_2 adsorbed and infected cps derivatives of YG2, although neither adsorption to nor infection of the parental strain YG2 by phiYA5_2 was observed. The plaque-surrounding halos formed by phiYA5_2 implied the presence of the virion-associated depolymerase that degrades the capsular polysaccharide of YA5. These results indicated that the capsular polysaccharide is a physical barrier rather than a binding receptor for phiYA5_2 and that phiYA5_2 specifically overcomes the capsular polysaccharide of YA5. Thus, it is suggested that tetragenococcal phages utilize CPSs as binding receptors and/or degrade CPSs to approach host cells. IMPORTANCE T. halophilus is a halophilic lactic acid bacterium that contributes to the fermentation processes for various salted foods. Bacteriophage infections of T. halophilus have been a major industrial problem causing fermentation failures. Here, we identified the cps loci in T. halophilus as genetic determinants of phage susceptibility. The structural diversity of the capsular polysaccharide is responsible for the narrow host ranges of tetragenococcal phages. The information provided here could facilitate future studies on tetragenococcal phages and the development of efficient methods to prevent bacteriophage infections.

Dose-response relationships of rabeprazole 5, 10, 20, and 40 mg once daily on suppression of gastric acid secretion through the night in healthy Japanese individuals with different CYP2C19 genotypes.

PURPOSE: This study was designed to investigate the antisecretory activity of rabeprazole administered once daily in doses of 5, 10, 20, and 40 mg and different cytochrome P450 2C19 (CYP2C19) genotypes on gastric pH in healthy individuals. Additional objectives were delineating the nighttime from the daytime effect and determining the relationships between the pharmacokinetics and pharmacodynamics of rabeprazole. METHODS: Eight individuals of each of the three genotypes of CYP2C19-homozygous extensive metabolizers (homo-EMs), heterozygous EMs (hetero-EMs), and poor metabolizers (PMs)-were recruited. Twenty-four individuals received a once-daily dose, with dosing interval 24 h of 5, 10, 20, or 40 mg rabeprazole for 5 days in a 4-period crossover fashion. Twenty-four-hour intragastric pH and plasma rabeprazole concentrations were determined on day 5. RESULTS: A dose-dependent increase in median pH and in pH 4 holding time was observed across all CYP2C19 genotypes. When rabeprazole was increased from 20 mg to 40 mg, the differences and 95% confidence intervals (CIs) of nighttime pH 4 holding time between 40 mg and 20 mg in homo-EMs, hetero-EMs, and PMs were 8.0% (-5.0% -21.0%), 28.7% (15.7% -41.6%), and 16.9% (3.9% -29.9%), respectively. The relationship between the area under the plasma concentration-time curve up to the last time point at which rabeprazole was quantifiable (AUC(0-t)) and the pH 4 holding time could be described using a sigmoid maximum effect (E(max)) model. CONCLUSIONS: Our data demonstrate that increasing rabeprazole dose up to 40 mg once daily results in an increasing pharmacodynamic effect, which is most apparent for the control of nocturnal gastric acid secretion.

Foot rubbing evaluation of friction between shoe and flooring.

A simple and inexpensive method to evaluate slip resistance that can be readily introduced into the workplace is required. In the present study, we investigated the relationship between a simple sensory evaluation of anti-slipperiness by foot rubbing in standing and sitting positions and the actual friction properties obtained with in situ measurements at slip onset and during sliding. We also verified the possibility of identifying a hazardous area with a high slip-induced fall risk by the sensory evaluation scores. At the foot rubbing tests, more than half of the 15 participants in experiments could adequately perceive the slip resistance using the proposed method without any education on its perception. Furthermore, hazard detection scores, where a friction coefficient of 0.2 was detected as hazardous area, were obtained from optimal cut-off points of receiver operatorating characteristic curves for the participants with friction perception capability. The scores were 28.7, 20.7, 24.7, and 52.3/100 for the slip onset while standing, sliding while standing, slip onset while sitting, and sliding while sitting, respectively. From the viewpoint of hazard detection accuracies, the standing position was a better way than the sitting although limited to participants with the capability of perceiving friction. Based on the analysis of how to apply forces, the participants who showed a small movement of the center of pressure while standing or an increase in the vertical load while sitting had the capability of perceiving friction.

Biohydrogen production by mixed culture of Megasphaera elsdenii with lactic acid bacteria as Lactate-driven dark fermentation.

Numerous attempts have been made to upscale biohydrogen production via dark fermentation (DF); however, the Achilles' heel of DF, i.e., lactic acid bacteria (LAB) contamination and overgrowth, hinders such upscaling. Key microbes are needed to develop a lactate-driven DF system that can serve as a lactate fermentation platform. In this study, the utility of Megasphaera elsdenii and LAB co-culturing in lactate-driven DF was evaluated. When inoculated simultaneously with LAB or after LAB culture, M. elsdenii achieved a stable hydrogen yield of 0.95-1.49 H2-mol/mol-glucose, approximately half that obtained in pure M. elsdenii cultures. Hydrogen production was maintained even at an initial M. elsdenii-to-LAB cell ratio of one-millionth or less. Moreover, M. elsdenii produced hydrogen via lactate-driven DF from unusable sugars such as xylose or cellobiose. Thus, M. elsdenii could be a Game changer instrumental in unlocking the full potential of DF.

Ribitol-Containing Wall Teichoic Acid of Tetragenococcus halophilus Is Targeted by Bacteriophage phiWJ7 as a Binding Receptor.

Tetragenococcus halophilus, a halophilic lactic acid bacterium, is used in the fermentation process of soy sauce manufacturing. For many years, bacteriophage infections of T. halophilus have been a major industrial problem that causes fermentation failure. However, studies focusing on the mechanisms of tetragenococcal host-phage interactions are not sufficient. In this study, we generated two phage-insensitive derivatives from the parental strain T. halophilus WJ7, which is susceptible to the virulent phage phiWJ7. Whole-genome sequencing of the derivatives revealed that insertion sequences were transposed into a gene encoding poly(ribitol phosphate) polymerase (TarL) in both derivatives. TarL is responsible for the biosynthesis of ribitol-containing wall teichoic acid, and WJ7 was confirmed to contain ribitol in extracted wall teichoic acid, but the derivative was not. Cell walls of WJ7 irreversibly adsorbed phiWJ7, but those of the phage-insensitive derivatives did not. Additionally, 25 phiWJ7-insensitive derivatives were obtained, and they showed mutations not only in tarL but also in tarI and tarJ, which are responsible for the synthesis of CDP-ribitol. These results indicate that phiWJ7 targets the ribitol-containing wall teichoic acid of host cells as a binding receptor. IMPORTANCE Information about the mechanisms of host-phage interactions is required for the development of efficient strategies against bacteriophage infections. Here, we identified the ribitol-containing wall teichoic acid as a host receptor indispensable for bacteriophage infection. The complete genome sequence of tetragenococcal phage phiWJ7 belonging to the family Rountreeviridae is also provided here. This study could become the foundation for a better understanding of host-phage interactions of tetragenococci.

Effect of Hot Water Bottles on Body Temperature during Magnetic Resonance Imaging in Dogs under General Anesthesia: A Retrospective Study.

Prevention of hypothermia induced by anesthesia and enhanced by low environmental temperatures is difficult in magnetic resonance imaging (MRI) examinations in dogs as forced warming devices, including magnetic materials, are not acceptable for use in the MRI room. A hot water bottle (HWB) can be carried into an MRI examination room and can contribute to the prevention or attenuation of hypothermia. Here, we retrospectively investigated the effects of HWB on body temperature during MRI examinations in dogs under general anesthesia (GA). From anesthesia records of the Veterinary Medical Teaching Hospital, Okayama University of Science, validated data of 100 dogs that underwent an MRI examination under GA were obtained and divided into the following two groups: one group received HWB, while the other did not. Decrease in rectal temperature 15 min after intubation was significantly smaller in the group using HWB than in the group without HWB. In conclusion, the use of hot water bottles might be one of the methods to attenuate hypothermia in the early period but should not be expected for complete prevention of hypothermia, and it was not recommendable necessarily for body temperature management during MRI examinations in dogs under general anesthesia.

An anatomical study of the skull, the dorsal and ventral nasal conchal bullae and paranasal sinuses in normal Noma horses: Computed tomographic anatomical and morphometric findings.

Noma horses have the smallest body size among native Japanese horses and are classified as pony breeds by their size. Additionally, the Japanese horse breeds are classified into a single lineage, which includes Mongolian horses. Great intraspecific differences reportedly exist in the head shapes of domesticated horses, which have been investigated in various horse breeds. The present study aimed to evaluate the size of the nasal conchal bullae, and the paranasal sinuses of Noma horses in relation to the skull dimensions using computed tomography. Reconstructed images of the heads of five adult Noma horses were used. Skull and paranasal sinus parameters were measured and analysed in relation to each other and were compared with the data in the literature on the skulls of various horse breeds. In comparison with pony breed, Shetland ponies and donkeys had a shorter nasal length than cranial length, while Noma horses had a longer nasal length than cranial length, similar to the larger breeds. In the nasal conchal bullae, Shetland ponies showed a negative correlation between the head and bullae size, while Noma horses, similar to larger breeds, had a positive correlation. In conclusion, our findings suggest that Noma horses, despite having a body size that belongs to the pony breed, had a distinguishing ratio of the skull and paranasal sinuses similar to that of the larger breeds. Our results provide information on the physiological morphology of the head and comparative anatomy based on genetic diversity in horses.

Development of a 16S rRNA gene primer and PCR-restriction fragment length polymorphism method for rapid detection of members of the genus Megasphaera and species-level identification.

The genus Megasphaera is relevant to the environment, human health and food, and renewable energy for the future. In this study, a primer set was designed for PCR-restriction fragment length polymorphism (RFLP) analyses to detect and identify the members of Megasphaera. Direct detection and identification were achieved for environmental samples and isolates.

Mass spectrometry of urinary ß2 microglobulin oligomer in patients with proteinuria.

Urinary ß2 microglobulin (ß2-m) is a marker of renal tubule dysfunction; however, ß2-m might become degraded under acidic conditions. To confirm the degradation and consequent deactivation of ß2-m under acidic conditions, we used matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) to detect the levels and forms of ß2-m in the urine samples of patients with high proteinuria (n = 21) and healthy subjects (n = 6). ß2-m was purified in crude form using immunoprecipitation. A signal of 11.74 kDa, corresponding to the molecular weight of ß2-m, was detected in all samples. In addition, several high-molecular-weight proteins were detected in a patient as integrals of the intensity at 11.74 kDa. These results indicate that posttranslational modifications of ß2-m might be involved in the pathological process of proteinuria. Therefore, MS can be used for monitoring proteinuria and predicting the risk of progression.

Comparative Genomics of Closely Related Tetragenococcus halophilus Strains Elucidate the Diversity and Microevolution of CRISPR Elements.

Tetragenococcus halophilus - a halophilic lactic acid bacterium - is frequently used as a starter culture for manufacturing fermented foods. Tetragenococcus is sometimes infected with bacteriophages during fermentation for soy sauce production; however, bacteriophage infection in starter bacteria is one of the major causes of fermentation failure. Here, we obtained whole-genome sequences of the four T. halophilus strains YA5, YA163, YG2, and WJ7 and compared them with 18 previously reported genomes. We elucidated five types of clustered regularly interspaced short palindromic repeat (CRISPR) loci in seven genomes using comparative genomics with a particular focus on CRISPR elements. CRISPR1 was conserved in the four closely related strains 11, YA5, YA163, and YG2, and the spacer sequences were partially retained in each strain, suggesting that partial deletions and accumulation of spacer sequences had occurred independently after divergence of each strain. The host range for typical bacteriophages is narrow and strain-specific thus these accumulation/deletion events may be responsible for differences in resistance to bacteriophages between bacterial strains. Three CRISPR elements, CRISPR1 in strains 11, YA5, YA163, and YG2, CRISPR2 in strain WJ7, and CRISPR2 in strain MJ4, were inserted in almost the same genomic regions, indicating that several independent insertions had occurred in this region. As these elements belong to class 1 type I-C CRISPR group, the results suggested that this site is a hotspot for class 1, type I-C CRISPR loci insertion. Thus, T. halophilus genomes may have acquired strain-specific bacteriophage-resistance through repeated insertion of CRISPR loci and accumulation/deletion events of their spacer sequences.

Noninvasive Thermographic Photographing as an Assessment of the State of Discomfort in a Dog Receiving Radiation Therapy.

In humans, radiation induces dilation of capillaries and inflammatory reactions to raise skin temperature. Thermography is used to detect abnormalities after radiation therapy (RT). However, in veterinary nursing, objective evaluation of the condition of dogs after RT using thermography has not been reported. We investigated the nasal irradiation temperature, behavioral changes, and post-irradiation pain scores in a dog receiving RT for intranasal tumors. The temperature of the nasal planum gradually increased after irradiation, reaching a significantly higher value at 120-240 min. The highest temperature was 42.3 °C and the average temperature increased by 4.4 °C. Behavioral analysis pre- and post-RT did not vary significantly. Post-RT pain levels evaluated by the pain scale ranged from 0 to 1 throughout. No veterinary treatment was provided. In humans, increased skin temperature after radiation causes psychological stress, i.e., pain and discomfort, but no such behavioral changes were observed in this case. Given individual differences in stress-related behaviors, such as pain and discomfort, assessing a dog's painfulness using only subjective methods, such as appearance and behavioral evaluation, is limited. We used thermography to assess changes in conditions not detectable by routine monitoring alone. This method is non-invasive, objective, and indispensable for providing appropriate care.

Establishment of a canine lens epithelial cell line.

Some immortalized lens epithelial cell lines have been established and are useful for molecular analysis. The establishment of additional cell lines must, however, enable a variety of in-vitro examinations. The objective of this study was to establish a new canine lens epithelial cell line by isolating CLC-1 cells from the lens tissue of a dog with cataracts. In CLC-1 cells, transforming growth factor beta (TGF-ß) treatment significantly decreased gene expression of an epithelial marker and elevated that of mesenchymal markers; these characteristics are similar to those of a human lens epithelial cell line. Interestingly, CLC-1 cells exhibited lower expression of an epithelial marker and higher expression of mesenchymal markers than an anterior lens capsule. These results suggest that CLC-1 cells were derived from a cell population that was committed to epithelial-mesenchymal transition in cataract lens tissue. In conclusion, CLC-1 cells could be useful for analyzing molecular pathogenesis in canine cataracts.

Certaines lignées de cellules épithéliales du cristallin immortalisées ont été établies et sont utiles pour analyse moléculaire. L'établissement de lignées cellulaires supplémentaires doit cependant permettre une variété d'examens in vitro. L'objectif de cette étude était d'établir une nouvelle lignée cellulaire épithéliale du cristallin canin en isolant les cellules CLC-1 du tissu du cristallin d'un chien atteint de cataracte. Dans les cellules CLC-1, le traitement par le facteur de croissance transformant bêta (TGF-ß) a significativement diminué l'expression génique d'un marqueur épithélial et élevé celle des marqueurs mésenchymateux; ces caractéristiques sont similaires à celles d'une lignée cellulaire épithéliale du cristallin humain. Fait intéressant, les cellules CLC-1 présentaient une expression inférieure d'un marqueur épithélial et une expression plus élevée de marqueurs mésenchymateux qu'une capsule antérieure du cristallin. Ces résultats suggèrent que les cellules CLC-1 étaient dérivées d'une population cellulaire qui était impliquée dans la transition épithéliale-mésenchymateuse dans le tissu du cristallin de la cataracte. En conclusion, les cellules CLC-1 pourraient être utiles pour analyser la pathogenèse moléculaire dans les cataractes canines.(Traduit par Docteur Serge Messier).

Local Hemodynamic Changes Immediately after Correction of an Aberrant Right Subclavian Artery in a Dog: A Contrast Computed Tomographic Study.

A 1-year-old female Akita dog was referred for intermittent regurgitation. Computed tomographic angiography (CTA) showed an aberrant right subclavian artery (ARSA), resulting in constriction of the esophagus. After surgical ligation of the ARSA, CTA showed that the ARSA was not enhanced by contrast medium, and that sufficient collateral circulation of the right forelimb was supplied through the vertebral artery. Furthermore, the right and left vertebral arteries merged into the basilar artery at the level of the atlas, and no abnormal expansion of the ventral spinal artery was observed. Overall, we demonstrated the importance of post-surgical CTA for identification of surgical complications, including the formation of abnormal vessel alterations.

Dysuria Associated with Non-Neoplastic Bone Hyperplasia of the Os Penis in a Pug Dog.

A three-year-old male Pug presented with a three-year history of urolithiasis and repeated urethral obstruction. Biochemical analysis, ultrasonography, and retrograde urethrocystography revealed probable portosystemic shunt and incomplete urethral obstruction due to uric acid ammonium calculi. Enhanced computed tomography (CT) revealed portosystemic shunt and proliferation of the osseous tissue of the os penis, which was surgically removed. Histopathologically, the excised osseous tissue comprised bland lamellar bone without atypia or inflammation. Hyperplasia of the os penis was diagnosed based on the image findings and histopathology. The dysuria improved postoperatively. This is the first report of dysuria associated with non-neoplastic bone hyperplasia of the os penis in a dog. Careful evaluation of the os penis by CT is needed for accurate diagnosis in case of repeated penile urethral obstruction.

Elevated urinary biopyrrin excretion and oxidative bilirubin metabolism during 24-hour ultramarathon running.

The oxidative metabolite of bilirubin, biopyrrin, is considered a useful candidate marker of oxidative stress in vivo. The present study examines whether urinary biopyrrin excretion is elevated and how general laboratory parameters are changed by long-duration running such as that involved in ultramarathons. Fifteen volunteer runners (12 males and 3 females; aged 44 +/- 9 years; means +/- SD) provided written informed consent to participate in this study. The 24-h experimental run was not a race against time but rather to determine the effects of running around a track for 24 h without sleep and sufficient rest. Blood and urine samples were obtained before (0 h), during (16 h), and immediately after (24 h) running for 24 h. All of the participants completed the run. The mean (+/- SD) distance run was 162.6 +/- 18.3 km. Mean urinary biopyrrin excretion values at 0, 16, and 24 h were 1.23 +/- 0.73, 2.55 +/- 0.95, and 4.00 +/- 1.50 U/g creatinine, respectively. Urinary biopyrrin excretion was positively and significantly correlated with the serum bilirubin concentration (p<0.05) and distance run (p<0.05). These results suggest that urinary biopyrrin excretion could be a useful marker of oxygen stress incurred during a 24-h ultramarathon.