[A Case of High-Grade Appendiceal Mucinous Neoplasm].

A 70-year-old woman underwent conservative treatment for abscess-forming appendicitis. A contrast-enhanced abdominal computed tomography(CT)revealed a cystic lesion at the appendiceal base while the abscess had disappeared posttreatment. With the diagnosis of a low-grade appendiceal mucinous neoplasm(LAMN), a laparoscopic-assisted ileocolic resection was performed. The appendix was distended with mucus in the lumen. Histopathological examination showed that the tumor cells were more atypical than that of low-grade appendiceal mucinous neoplasm. There were no findings of adenocarcinoma, such as invasive growth. Therefore, high-grade appendiceal mucinous neoplasm(HAMN)was diagnosed. HAMN is a term advocated by Carr et al in 2016 to classify appendiceal mucinous neoplasm and was noted as a new category of mucinous tumors among appendiceal epithelial tumors in the fifth edition of the 2019 revised WHO classification. HAMN is a rare disease and only one case has been reported in Japan. It has not yet been noted in the Japanese Colorectal Cancer Treatment Manual. Here, we report this rare case with a review of the study.

[Clinical Experience with 13 Cases of Primary Small Bowel Adenocarcinoma].

Between 2003 and 2017, 13 patients with primary small bowel adenocarcinoma(SBA)were treated at our hospital. Tumors developed in the duodenum in 6 patients and in the jejunum in 7 patients. The median age of the patients was 62 (range: 31-83)years and male/female ratio was 10/3. Initial symptoms were obstruction in 5 patients, bleeding in 3 patients, and abdominal pain in 1 patient. The median diameter of tumor was 50(range: 23-100)mm. Concerning surgical margin, R0 resection was in 8 patients, R1 resection in 3 patients, and R2 resection in 2 patients. The number of patients with stage 0 disease was 1, stage Ⅱ was 2, stage Ⅲ was 6, and stage Ⅳ was 4. Chemotherapy was provided to 8 patients. The median survival time was 31.6(range: 1-118)months and 5-year survival rate were 26.9%. Four patients survived longer than 4 years without recurrence. Although there is no treatment established for SBA, it was thought that proactive resection and chemotherapy can be anticipated in these patients to bring about an improved survival.

[A Case of Adenocarcinoma Arising from Ectopic Gastric Mucosa in Meckel's Diverticulum with Abdominal Wall Abscess].

A 47-year-old woman visited a neighboring hospital because of lower abdominal pain and high fever. She was diagnosed with acute pyelonephritis and administered(oral)antibiotics. However, there was no sign of improvement. She was referred to our hospital for closer examination. Computed tomography revealed an 8 cm abdominal wall abscess spreading from the prevesical space to the rectus abdominis. Incisional drainage was performed under local anesthesia. She developed rectus abdominis muscle diastasis, and a laparotomy was performed 2 months later. Intraoperative findings showed that her Meckel's diverticulum was continuous with the abdominal wall abscess. Diagnosed with Meckel's diverticulitis with abdominal wall abscess, the patient underwent surgery(excision)for these. Histopathological findings showed adenocarcinoma cells in the abscess tissue and were continuous with gastric pyloric gland-like tissue in Meckel's diverticulum. Based on these findings, the patient was diagnosed with adenocarcinoma arising from ectopic gastric mucosa in the Meckel's diverticulum. The patient received postoperative adjuvant chemotherapy for a year. The patient is currently alive and has not experienced recurrence for 2 years since surgery. It is difficult to diagnose carcinoma of Meckel's diverticulum preoperatively due to late onset of symptoms. The diagnosis is often made at the advanced stage, when the prognosis is poor. This case is rare due to the incidental finding of an abdominal abscess and the absence of recurrence 2 years after surgery.

[A Case of Sigmoid Colon Cancer with Synchronous Liver Metastasis, Treated with Laparoscopic Liver Resection after SOX plus BV Chemotherapy].

We performed laparoscopic liver resection in a patient with synchronous liver metastasis from advanced sigmoid colon cancer after induction with S-1 plus oxaliplatin (SOX) plus bevacizumab (BV) chemotherapy. A 61-year-old woman underwent laparoscopy-assisted sigmoidectomy for locally advanced sigmoid colon cancer with synchronous liver metastasis. SOX plus BV chemotherapy was initiated. After 3 courses, the liver tumor was downsized, and metastasectomy was performed laparoscopically with R0 resection. The postoperative course was uneventful and the patient was discharged on the 11th postoperative day. She has been free from recurrence. Induction with SOX plus BV chemotherapy is considered to be not only effective, but also beneficial for maintaining the quality of life (QOL) in patients with advanced colorectal cancer.

Cystic duct with no visible signal on magnetic resonance cholangiography is associated with laparoscopic difficulties: an analysis of 695 cases.

BACKGROUND/AIMS: We investigated the association between the magnetic resonance cholangiography (MRC) results and surgical difficulties and bile duct injuries during laparoscopic cholecystectomy (LC). METHODS: MRC was performed on 695 consecutive patients before LC. We divided the patients into two groups (visible cystic duct group and "no signal" cystic duct on MRC group) and compared them with regard to the length of the operation, conversion rate to open cholecystectomy (OC) and rate of bile duct injury. RESULTS: The "no signal" cystic duct on MRC group had a longer operation and higher rate of conversion to OC compared with the visible cystic duct group. However, there was no statistically significant difference in the occurrence rate of bile duct injury between the two groups. CONCLUSIONS: The "no signal" cystic duct on MRC group was associated with laparoscopic difficulties, but not with an increased rate of biliary injury. When a visible cystic duct is not observed on MRC an early conversion to open surgery may avoid a bile duct injury during LC.

Duplicate appendix complicated by low-grade appendiceal mucinous neoplasm: a rare case report and review of the literature.

Low-grade appendiceal mucinous neoplasms (LAMNs) have been a very controversial tumor, and there is a lack of standardization for the optimal surgical procedure due to the infrequency of this disease. This is the first case report of duplicate appendix complicated by LAMN. The preoperative imaging examinations revealed that the mucinous tumor was shrinking spontaneously, allowing for safe laparoscopic resection. The histopathological findings indicated a dilated common base of the duplicated appendix, suggesting that the mucinous content drained spontaneously to the cecum. Further studies of the various complications of LAMNs are needed to establish the optimal surgical approach for LAMNs.

Feedback regulation of MAPK signalling by an RNA-binding protein.

Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved enzymes that convert extracellular signals into various outputs such as cell growth, differentiation and cell death. MAPK phosphatases selectively inactivate MAPKs by dephosphorylating critical phosphothreonine and phosphotyrosine residues. The transcriptional induction of MAPK phosphatase expression by various stimuli, including MAPK activation, has been well documented as a negative-feedback mechanism of MAPK signalling. Here we show that Rnc1, a novel K-homology-type RNA-binding protein in fission yeast, binds and stabilizes Pmp1 messenger RNA, the MAPK phosphatase for Pmk1 (refs 10, 11). Rnc1 therefore acts as a negative regulator of Pmk1 signalling. Notably, Pmk1 phosphorylates Rnc1, causing enhancement of the RNA-binding activity of Rnc1. Thus, Rnc1 is a component of a new negative-feedback loop that regulates the Pmk1 pathway through its binding to Pmp1 mRNA. Our findings--the post-transcriptional mRNA stabilization of a MAPK phosphatase mediated by an RNA-binding protein--provide an additional regulatory mechanism for fine-tuning of MAPK signalling pathways.

External transcutaneous ultrasound technique in the equine cricoarytenoideus dorsalis muscle: Assessment of muscle size and echogenicity with resting endoscopy.

BACKGROUND: Recent studies have assessed the cricoarytenoideus dorsalis muscle (CAD) using transoesophageal ultrasonography in equine recurrent laryngeal neuropathy (RLN). We assessed the CAD using the external transcutaneous ultrasound technique, which may constitute an easier method in horses. OBJECTIVES: To evaluate ultrasonographic imaging of the left cricoarytenoideus dorsalis muscle (LCAD) and right cricoarytenoideus dorsalis muscle (RCAD) as a diagnostic tool for RLN using the transcutaneous ultrasound technique. STUDY DESIGN: Cross-sectional study. METHODS: The axial plane thickness, cross-sectional area and echogenicity of the LCAD and RCAD were measured using transcutaneous ultrasonography in 164 horses. Assessments of LCAD were compared with those of RCAD. The LCAD:RCAD ratios in thickness and area were compared between control horses (resting grades 1 and 2) and horses with resting laryngeal grades 3 and 4 using the Havemeyer 4-point grading system with subgrades. RESULTS: The LCAD:RCAD ratios for thickness and area were 0.69 and 0.66 in horses with resting grades 3 and 4 respectively; LCAD was more hyperechogenic than RCAD in resting grades 3 and 4. LCAD:RCAD ratios for thickness and area in grades 3.II, 3.III and 4 were significantly lower than those in control horses. Thickness and area of the LCAD were negatively correlated with resting laryngeal grade MAIN LIMITATIONS: Overground endoscopy was not performed in this study. There were some differences in methodology: measurement of the physical thickness of the LCAD and clipping of hair at the laryngeal region were only performed in horses that underwent laryngoplasty. CONCLUSIONS: Results of ultrasonographic assessments of the CAD using transcutaneous ultrasonography were similar to those obtained by transoesophageal ultrasonography. This technique enables a simple, noninvasive, direct and easy examination. Assessment of the CAD using transcutaneous ultrasonography may be a useful technique and a potential option for determining whether to perform nerve graft or laryngoplasty.

Role of nitrergic nerves in the regulation of motility of the omasum and abomasum in healthy sheep (Ovis aries).

We examined the physiological role of nitrergic nerves in the regulation of omasal and abomasal motility in conscious healthy sheep and omasal muscle specimens. Nitric oxide (NO)-donor, S-nitroso-acethyl-dl-penicillamine (SNAP, 3-30 nmol/kg per min, i.v.) significantly inhibited omasal electromyographic (EMG) activity, whereas it did not alter EMG activity in the abomasal antrum. However, NO synthase inhibitor, Nomega-nitro-l-arginine-methyl ester (L-NAME, 0.3-3.0 micromol/kg per min, i.v.) did not alter EMG activity of the omasum and abomasum. In the in vitro experiments, SNAP application (6-200 micromol/l) significantly inhibited bethanechol (10 micromol/l)-induced contraction of longitudinal and circular muscles of the omasum. L-NAME application (0.03-3.0 mmol/l) enhanced electric field stimulation-induced contractions of the circular muscles. The results suggest that the omasal muscles are responsive to exogenous NO and that nitrergic nerves innervate the circular muscle layer of the omasum, however, nitrergic nerves are not or scarcely involved the physiological regulation of omasal and possibly abomasal motility in healthy sheep.

CCAAT/enhancer binding protein-beta promotes the survival of intravascular rat pancreatic tumor cells via antiapoptotic effects.

A transcriptional factor, CCAAT/enhancer binding protein-beta (C/EBP-beta), regulates a variety of cell functions in normal and neoplastic cells. Although the involvement of C/EBP-beta in metastasis has been demonstrated clinicopathologically in several types of human cancer, the mechanism by which it functions during the multistep process of metastasis remains largely unknown. We investigated the role of C/EBP-beta in the intravascular step of hematogenous metastasis in a rat pancreatic tumor cell line, AR42J-B13, as this step profoundly affects metastatic efficiency. C/EBP-beta-transfected AR42J-B13 (betaB13) cells acquired considerable resistance against serum toxicity, which was primarily mediated by apoptosis in vitro. Upregulated expression of Bcl-2 and Bcl-xL was seen in betaB13 cells. Enhanced early survival of intraportally injected betaB13 cells in the BALB/c nu/nu male mice liver, detected by the mRNA of a vector-specific gene, was observed. Nick-end labeling analysis of the tumor-injected liver revealed significantly lower rates of apoptosis among intravascular betaB13 tumor cells than among empty vector-transfected AR42J-B13 (mB13) cells. Finally, intrasplenically injected betaB13 cells established a larger number of colonies in the liver than did the mB13 cells. These findings suggest that C/EBP-beta may enhance hematogenous metastasis and its antiapoptotic effects may promote the survival of intravascular tumor cells.

Multiple early gastric cancer with duodenal invasion.

BACKGROUND: Early gastric cancers with duodenal invasion are rare, and no previous case of multiple early gastric cancer, one invading the duodenal bulb, has been reported. CASE PRESENTATION: A 79-year-old woman was investigated for upper abdominal discomfort. Endoscopic examination revealed an irregular nodulated lesion in the antrum area, and a reddish aggregated-type semi-circumferential nodulated lesion extending from the prepyloric area to the duodenal bulb through the normal mucosa with the antrum lesion. Biopsy revealed a tubular adenoma for the antrum lesion and a well-differentiated tubular adenocarcinoma for the prepyloric lesion. Distal gastrectomy with sufficient duodenal resection was performed. Microscopically, the antrum lesion appeared as a papillary adenocarcinoma, and the prepyloric lesion as a mainly papillary adenocarcinoma which partially invaded the submucosa without any sequential elongation for endoscopic findings. The lesion extended into the duodenal bulb, and was 12 mm in length from the oral end of Brunner's gland's area and limited within the duodenal mucosa. CONCLUSION: Here, we present an unusual case of multiple early gastric cancer, one of which invaded the duodenum with relative wide mucosal spreading. This case illustrates that even early stage cancers located in the gastric antrum, particularly in the prepyloric area can invade the duodenum directly.

Evaluation of the relationship between the minimum inhibitory concentration of ceftiofur and third-generation cephalosporins in Escherichia coli isolates from food-producing animals.

To enable future comparison of the antimicrobial susceptibility data between bacteria obtained from animals and humans, it is necessary to compare the relationships between minimum inhibitory concentrations (MICs) of veterinary and human medicine. We evaluated the relationship between the MIC of ceftiofur (CTF) and the MICs of other third-generation cephalosporins (TGCs): cefotaxime (CTX), cefpodoxime (CPDX), and ceftazidime (CAZ), determined by the broth microdilution method using 118 cefazolin-resistant Escherichia coli isolates from food-producing animals. Using the Clinical and Laboratory Standards Institute criteria, very major classification errors were observed only in CAZ (17.8%, 21 of 118); major and minor errors were observed in all TGCs (CTX: 0.8% [1 of 118] and 9.3% [11 of 118]; CPDX: 9.3% [11 of 118] and 6.8% [8 of 118]; CAZ: 2.5% [3 of 118] and 9.3% [11 of 118], respectively). The Spearman correlation coefficients between the MICs of CTF and CTX, CPDX, and CAZ were 0.765, 0.731, and 0.306, respectively. The sensitivity and specificity values were 100.0% and 81.8% for CTX, 99.0% and 27.3% for CPDX, and 76.0% and 86.4% for CAZ compared with CTF. The C-statistic was 0.978 for CTF and CTX, 0.953 for CPDX, and 0.798 for CAZ. For the TGCs evaluated in our study, testing for CTX susceptibility results showed the highest correlation with the results given when testing for CTF susceptibility.

Localization and secretion of epidermal growth factor in the parotid gland and its intragastric kinetics in sheep.

Ruminants secrete a large quantity of saliva that is rich in electrolytes; however, it remains unclear whether their parotid saliva contains epidermal growth factor (EGF). The present study was set up to examine the distribution of EGF and transforming growth factor-alpha (TGF-alpha) in the ovine parotid and submandibular glands and the salivary secretion of EGF-like binding activity (EGF-LBA) as the sum of EGF and TGF-alpha in conscious sheep. We also measured changes in the intragastric concentration of EGF-LBA in the ovine rumen and abomasum, and examined the effect of bilateral diversion of parotid saliva on intragastric EGF-LBA concentration in sheep. Both the ovine parotid and, to a lesser extent, the submandibular glands contained EGF-LBA. Immunohistochemical study showed that EGF and TGF-alpha-immunoreactivities were localized in the ductal epithelium in both glands. Transcriptional expression of EGF and TGF-alpha mRNA was demonstrated in both glands by reverse transcription-polymerase chain reaction (RT-PCR). In conscious sheep, the parotid gland continuously secreted EGF-LBA in the saliva before feeding, and the secretion of parotid EGF-LBA was markedly increased during feeding. After diversion of the parotid saliva for 1 week, EGF-LBA concentration in the ruminal fluid, but not in the abomasal fluid, decreased in the postprandial period, indicating that parotid EGF-LBA is a primary source of EGF-LBA for the rumen fluid during the postprandial period in sheep. Moreover, RT-PCR detected the expression of TGF-alpha mRNA in the rumen and abomasum and that of EGF in the abomasum, implying that these stomachs possibly supply, in part, EGF-LBA to the luminal fluid.

Safety of argon plasma coagulation for hemostasis during endoscopic mucosal resection.

Showing the safety of argon plasma coagulation (APC) over mucosal defects during/after endoscopic mucosal resection (EMR), 2 studies using resected pig (ex vivo) and living minipig (in vivo) stomachs were performed. As an ex vivo study, APC was applied over mucosal defects in 2 groups; with prior submucosal saline injection and without injection. Only subtle tissue damage was observed in the injection group, whereas apparent damage was observed in the noninjection group. The damaged distances in depth significantly increased as the pulse duration increased and those at the pulse duration of 4 seconds, which might be maximal in clinical practice, were approximately 1 mm. As an in vivo study, APC was applied over mucosal defects immediately after EMR. Only subtle tissue damage was observed even at the pulse duration of 20 seconds as shown in the ex vivo study. APC can be performed safely over the mucosal defects during/after EMR.

Submucosal injection of normal saline may prevent tissue damage from argon plasma coagulation: an experimental study using resected porcine esophagus, stomach, and colon.

Argon plasma coagulation (APC) is considered to be a safe thermocoagulation technique, but some reports show perforation and deformity during and after APC. In this study, we investigated the usefulness of prior submucosal injection for APC. APC over the mucosa was performed on fresh resected porcine esophagus, stomach, and colon with prior submucosal injection of normal saline (injection group) and without it (control group). The depth of tissue damage increased linearly with pulse duration up to the shallower submucosal layer in both groups. After that, tissue damage in the injection group remained confined to the shallower submucosal layer under any condition, whereas that in the control group continued to extend. The tissue damages of the injection groups were significantly (P<0.05) shallower than those of the control groups that reached the deeper submucosal layer in all the organs. Submucosal injection of normal saline before the application of APC may limit tissue damage and prevent perforation and deformity.

Introduction of wild-type patched gene suppresses the oncogenic potential of human squamous cell carcinoma cell lines including A431.

Defects in a developmental signaling pathway involving the mammalian homologue of the Drosophila segment polarity gene, patched are associated with human tumors such as basal cell carcinoma, medulloblastoma and squamous cell carcinoma. Loss of heterozygosity (LOH) in some of these tumor cells suggests that patched functions as a tumor suppressor gene. To evaluate the biological significance of patched mutations in human sporadic tumor cells, we constructed a VSV-G pseudotyped retrovirus vector carrying the wild-type patched gene and transduced it into two human squamous cell carcinoma (SCC) cell lines, A431 and KA, that express only mutant patched mRNA. When SSC cells were transduced with Ptc virus, colony forming activity in soft agar was drastically reduced and these cells recovered anchorage independent growth when Sonic hedgehog (Shh), the ligand of Patched (Ptc), was added into the soft agar culture. Expression of exogenous patched, however, had no effect on anchorage independent growth of Ras-transformed NIH3T3 cells or SCC cell line, NA, which expresses wild-type patched mRNA. Cyclopamine, a specific inhibitor of the Shh/Ptc/Smo signaling pathway, efficiently suppressed anchorage independent growth of A431 and KA cells. These results indicate that loss of patched function plays a major role in the acquisition of oncogenic potential in these SCCs and further that Ptc virus would be an effective reagent for suppressing tumorigenicity of such SCCs.

Should the extrahepatic bile duct be resected for locally advanced gallbladder cancer?

BACKGROUND: The incidence and mode of spread of carcinoma of the gallbladder into the hepatoduodenal ligament have not been well described pathologically for gallbladder carcinoma extending into the subserosa and beyond. METHODS: Between 1985 and 2002, 50 consecutive patients with gallbladder carcinoma extending into the subserosa or beyond underwent radical surgery, including extrahepatic bile duct resection. Serial sections of specimens of the resected extrahepatic bile ducts were examined to determine the incidence and the pattern of invasion of the hepatoduodenal ligament from the primary cancer. RESULTS: Invasion of the hepatoduodenal ligament was present in 30 of the 50 specimens. Of these, 9 showed direct extramural spread (type I), 4 showed continuous intramural spread (type II), 5 showed distant spread separated from the primary tumor (type III), and 4 showed spread of cancer cells from metastatic lymph nodes (type IV). The remaining 8 patients had more than 1 type: 1 patient had types I + III; 3 had types I + III + IV; and 4 had types III+IV. Invasion of the hepatoduodenal ligament was present in 24 of 44 patients without preoperative obstructive jaundice and in 2 of 13 patients with stage IB disease. Patients with types II, III, and IV spread into the hepatoduodenal ligament had significantly better survival than those with type I spread. CONCLUSIONS: Gallbladder carcinoma extending into the subserosa or beyond invades the hepatoduodenal ligament with relatively high frequency. Preoperative diagnosis of this invasion is difficult; therefore, strong consideration should be given to resection of the extrahepatic bile ducts and lymph nodes.

Unique roles of G protein-coupled histamine H2 and gastrin receptors in growth and differentiation of gastric mucosa.

Disruption of histamine H2 receptor and gastrin receptor had different effects growth of gastric mucosa: hypertrophy and atrophy, respectively. To clarify the roles of gastrin and histamine H2 receptors in gastric mucosa, mice deficient in both (double-null mice) were generated and analyzed. Double-null mice exhibited atrophy of gastric mucosae, marked hypergastrinemia and higher gastric pH than gastrin receptor-null mice, which were unresponsive even to carbachol. Comparison of gastric mucosae from 10-week-old wild-type, histamine H2 receptor-null, gastrin receptor-null and double-null mice revealed unique roles of these receptors in gastric mucosal homeostasis. While small parietal cells and increases in the number and mucin contents of mucous neck cells were secondary to impaired acid production, the histamine H2 receptor was responsible for chief cell maturation in terms of pepsinogen expression and type III mucin. In double-null and gastrin receptor-null mice, despite gastric mucosal atrophy, surface mucous cells were significantly increased, in contrast to gastrin-null mice. Thus, it is conceivable that gastrin-gene product(s) other than gastrin-17, in the stimulated state, may exert proliferative actions on surface mucous cells independently of the histamine H2 receptor. These findings provide evidence that different G-protein coupled-receptors affect differentiation into different cell lineages derived from common stem cells in gastric mucosa.

Structural and functional characterization of gastric mucosa and central nervous system in histamine H2 receptor-null mice.

To examine the physiological role of the histamine H(2) receptor, histamine H(2) receptor-null mice were generated by homologous recombination. Histamine H(2) receptor-null mice, which developed normally and were fertile and healthy into adulthood, exhibited markedly enlarged stomachs and marked hypergastrinemia. The former was due to hyperplasia of gastric gland cells (small-sized parietal cells, enterochromaffin-like cells and mucous neck cells which were rich in mucin), but not of gastric surface mucous cells, which were not increased in number as compared with those in wild-type mice despite the marked hypergastrinemia. Basal gastric pH was slightly but significantly higher in histamine H(2) receptor-null mice. Although carbachol but not gastrin induced in vivo gastric acid production in histamine H(2) receptor-null mice, gastric pH was elevated by both muscarinic M(3) and gastrin antagonists. Thus, both gastrin and muscarinic receptors appear to be directly involved in maintaining gastric pH in histamine H(2) receptor-null mice. Interestingly, gastric glands from wild-type mice treated with an extremely high dose of subcutaneous lansoprazole (10 mg/kg body weight) for 3 months were very similar to those from histamine H(2) receptor-null mice. Except for hyperplasia of gastric surface mucous cells, the findings for gastric glands from lansoprazole-treated wild-type mice were almost identical to those from gastric glands from histamine H(2) receptor-null mice. Therefore, it is possible that the abnormal gastric glands in histamine H(2) receptor-null mice are secondary to the severe impairment of gastric acid production, induced by the histamine H(2) receptor disruption causing marked hypergastrinemia. Analyses of the central nervous system (CNS) of histamine H(2) receptor-null mice revealed these mice to be different from wild-type mice in terms of spontaneous locomotor activity and higher thresholds for electrically induced convulsions. Taken together, these results suggest that (1) gastrin receptors are functional in parietal cells in histamine H(2) receptor-null mice, (2) abnormal gastric glands in histamine H(2) receptor-null mice may be secondary to severe impairment of gastric acid production and secretion and (3) histamine H(2) receptors are functional in the central nervous system.

Comparison of in vitro activities and pharmacokinetics/pharmacodynamics estimations of veterinary fluoroquinolones against avian pathogenic Escherichia coli isolates.

We analyzed in vitro activities and pharmacokinetics/pharmacodynamics (PK/PD) parameters of veterinary fluoroquinolones against avian pathogenic Escherichia coli (APEC) strains from cases of avian colibacillosis. The median of minimum inhibitory concentration (MIC(50)) values against APEC strains for enrofloxacin (ERFX) and danofloxacin (DNFX) were 0.25 µg/ml and for norfloxacin (NFLX) and ofloxacin (OFLX) were 0.5 µg/ml. The percentage of resistant strains for ERFX, DNFX, NFLX, and OFLX were 24.4%, 23.6%, 22.8%, and 23.6%, respectively. Scattergrams of the MICs of ERFX compared to DNFX, NFLX, and OFLX for 127 strains demonstrate a clear correlation between the MIC of ERFX and that of other fluoroquinolones. The differences in amino acid substitution in GyrA may play a role in the variation of MIC values for fluoroquinolones. The ratios of peak serum concentration to MIC (C(max):MIC) and ratios of area under the curve to MIC (AUC:MIC) were relatively high in ERFX and OFLX compared to other fluoroquinolones. These results indicate that although the in vitro activities of these fluoroquinolones against APEC isolates are slightly different, the PK/PD values vary with PK parameters. Therefore, we need to consider the PK/PD parameters in the choice of fluoroquinolones during treatment of avian colibacillosis.