Fuzapladib reduces postsurgical inflammation in the intestinal muscularis externa.

Postoperative ileus (POI) is a surgical complication that induces emesis and anorexia. Fuzapladib (FUZ), an inhibitor of leukocyte-function-associated antigen type 1 (LFA-1) activation, a leukocyte adhesion molecule, exerts anti-inflammatory effects by inhibiting leukocyte migration into the inflammatory site. In this study, we examined the prophylactic impact of FUZ on POI in a mouse model. POI model mice were generated by intestinal manipulation, and the effect of FUZ on intestinal transit and the infiltration of inflammatory cells into the ileal muscularis externa was assessed. The increased number of macrophages was significantly suppressed by FUZ, whereas the infiltration of neutrophils into the ileal muscularis externa was not sufficiently inhibited in the POI model mice. Additionally, FUZ did not ameliorate delayed gastrointestinal transit in POI model mice. In conclusion, our results suggest that FUZ does not improve delayed gastrointestinal transit but partially inhibits inflammation in the ileal muscularis externa in POI model mice. FUZ may be a potential anti-inflammatory agent for the management of post-surgical inflammation.

Sclerosing encapsulating peritonitis in a dog with pancreatic ductal adenocarcinoma.

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a rare clinical syndrome characterised by fibrosis and thickening of the peritoneum with massive adhesions of the abdominal organs. In humans, abdominal tumours, such as pancreatic adenocarcinoma, can be underlying diseases of SEP. This report describes a case of SEP in a dog with pancreatic ductal adenocarcinoma. CASE PRESENTATION: An 11-year-old male neutered French Bulldog presented with chronic vomiting. Ultrasonography revealed a mass in the centre of the abdomen. A small amount of ascites, interpreted as modified transudate, was present in the abdominal cavity. Computed tomography (CT) revealed peritoneal effusion with a thickened peritonium. Laparoscopy revealed a large nodular lesion occupying the central portion of the abdomen, continuous with the falciform ligament. Histological examination of the biopsy specimens of the mass, abdominal wall, and gastric peritoneum revealed marked fibroplasia with mild lymphoplasmacytic infiltrates. Based on these results, a tentative diagnosis of early stage sclerosing encapsulating peritonitis (SEP) was made. Prednisolone and tamoxifen were administered with the expectation of ameliorating SEP, however, the dog died 61 days post diagnosis. At autopsy, the intestinal loop and mesentery were encased in the fibrous membrane, which is a typical finding in SEP. Histopathology and immunohistochemistry of the samples obtained at autopsy supported the diagnosis of pancreatic ductal adenocarcinoma with peritoneal dissemination and distant metastasis with desmoplasia. The unexpectedly hardened skin, where previously laparoscopic ports were inserted, histologically contained the same carcinoma cells with desmoplasia. CONCLUSIONS: To the best of our knowledge, this is the first report of canine SEP with pancreatic ductal adenocarcinoma that also caused metastasis to port insertion sites as well as distant organs.

The validity of anesthetic protocols for the surgical procedure of castration in rats.

To achieve surgical anesthesia in animal experimentation, it is necessary to select the appropriate anesthetic protocol by considering its pharmacological properties and the surgical procedure to be performed. However, few studies have investigated the validity of anesthetic protocols under surgical conditions in small rodents. The present study aimed to clarify the pharmacological properties of 4 anesthetic protocols during the surgical procedure of castration in rats. Eight-week-old male Wistar rats were anesthetized with anesthetics, including the combination of ketamine and xylazine (K/X), the combination of medetomidine, midazolam, and butorphanol (M/M/B), isoflurane, and sevoflurane. Castration was performed under each anesthesia, and anesthetic depth and times were assessed, as were vital signs. The injectable anesthetics were investigated at standard and high doses. The concentration of inhalant anesthetics was adjusted to 1.5 minimum alveolar concentration (MAC). K/X at both doses demonstrated sufficient anesthetic depth with rapid induction and recovery. However, bradycardia and hypothermia were prominent in high-dose K/X, indicating that the standard-dose is more appropriate for surgical anesthesia in castration procedures. M/M/B demonstrated high anesthetic sensitivity variation in individual animals. In contrast to injectable anesthetics, inhalant anesthetics provided stable anesthetic depth with less cardiorespiratory influence. Sevoflurane did not lead to a significant decrease in rectal temperature during the anesthetic period. Results of the present study revealed the optimal dose and pharmacological features of several anesthetic protocols for castration, and may contribute to the standardization of surgical anesthesia in rats.

The anti-inflammatory action of maropitant in a mouse model of acute pancreatitis.

The neurokinin 1 receptor (NK1R) plays an important role in the pathogenesis of acute pancreatitis (AP). Maropitant is an NK1R antagonist that is widely used as an antiemetic in dogs and cats. In the present study, we investigated the anti-inflammatory action of maropitant in a mouse model of AP. AP was induced in BALB/c mice by intraperitoneal administration of cerulein, and maropitant was administered subcutaneously at a dose of 8 mg/kg. We assessed the mRNA expression levels of NK1R and substance P (SP) in the pancreatic tissue via real-time reverse transcription polymerase chain reaction. In addition, the effect of maropitant on plasma amylase, lipase, and interleukin-6 (IL-6) levels was measured in each mouse. Inflammatory cell infiltration in the pancreas was assessed by myeloperoxidase (MPO) staining. Our results showed that AP induction significantly elevated the mRNA expression of SP in the pancreatic tissue. Treatment with maropitant significantly lowered plasma amylase and IL-6 levels. In addition, treatment with maropitant inhibited the infiltration of MPO-positive cells in the pancreas. The present study suggests that maropitant possesses an anti-inflammatory activity, in addition to its antiemetic action.

Transrectal guidance of the ovaries reduces operative time during bovine laparoscopic ovariectomy.

The main objective of this study was to evaluate the effects of transrectal guidance of the ovaries by an assistant on operative time during bovine laparoscopic ovariectomy. Twenty four clinically healthy Holstein dairy cows were divided randomly into two groups. In the transrectal guidance group, an assistant grasped the ovaries via the transrectal route and pulled them to a position where they could be visualized with a camera. On the other hand, the control group was operated without guidance. The time required to remove both ovaries in the guidance group was shorter than that in the control group (P<0.01). We concluded that laparoscopic ovariectomy with transrectal guidance of the ovaries can substantially shorten operative time, thereby greatly contributing to animal welfare and to reducing the burden on the operator.

Pharmacological properties of various anesthetic protocols in 10-day-old neonatal rats.

In general, the anesthesia in neonates involves high risk. Although hypothermic anesthesia is recommended in rats up to the age of 7 days, neonatal anesthesia for later periods has not been standardized. The present study investigated the pharmacological properties of conventional anesthetic protocols in 10-day-old SD rats. The rats were anesthetized with four anesthetics: a combination of ketamine and xylazine (K/X); a combination of medetomidine, midazolam, and butorphanol (M/M/B); isoflurane; and sevoflurane. Anesthetic depth was scored by reflex response to noxious stimuli. Induction and recovery times were recorded. Vital signs and mortality rate were evaluated for safety assessment. All rats died after administration of K/X at a dose of 60/6 mg/kg, whereas K/X at 40/4 mg/kg resulted in insufficient anesthetic depth, indicating inappropriate for neonatal anesthesia. Although M/M/B at the adult rat dose (0.15/2/2.5 mg/kg) did not provide surgical anesthetic depth, the mouse dose (0.3/4/5 mg/kg) showed sufficient anesthetic depth with relatively stable vital signs. Isoflurane required a long induction period, and caused remarkable respiratory depression and hypothermia, resulted in a 25% mortality rate. In contrast, sevoflurane provided consistent surgical anesthetic depth with rapid induction. Although respiratory rate decrease was markedly observed, all rats survived. Among the anesthetic protocols investigated in the present study, sevoflurane and M/M/B at the mouse dose were recommended for the neonatal anesthesia. Compared with adult rats, the required dose of both anesthetics in neonates was higher, possibly associated with their lower anesthetic sensitivity.

A nasal osteoma with an acute course in a Japanese Black heifer.

A 14-month-old Japanese Black heifer presented with unilateral epistaxis and mild swelling of the right face. Radiography revealed a mass with increased radiopacity on the right side of the nasal bridge, extending to the left side. Intranasal endoscopy confirmed a large tumor-like structure protruding into the nasal cavity. Following euthanasia, cranial computed tomography (CT) was performed, revealing a tumor 24.3 × 17.5 × 14.8 cm in size. The tumor occupied the entire right nasal cavity and the frontal and sphenoid sinuses. Histopathological examination revealed that the tumor consisted of well-differentiated trabecular bones and loose connective tissue. Based on these findings, a diagnosis of osteoma was established. This report describes a case of osteoma with an acute course in a Japanese Black heifer.

The 5-HT3 Receptor Antagonist Ondansetron Attenuates Pancreatic Injury in Cerulein-Induced Acute Pancreatitis Model.

The 5-hydroxytryptamine-3 receptor (5-HT3R) antagonist ondansetron has been clinically approved as an anti-emetic agent. Recent findings indicate that ondansetron has anti-inflammatory properties. The aim of the present study was to assess the therapeutic action of ondansetron in cerulein-induced acute pancreatitis model. Male-BALB/c mice were used in the present study. Acute pancreatitis was induced by an hourly injection of cerulein. Ondansetron was administered subcutaneously at a dose of 3 mg/kg. The messenger RNA (mRNA) expression of 5-HT3 R in pancreatic tissue was assessed with RT-PCR. Plasma amylase, lipase, and interleukin (IL)-6 levels were evaluated. Pancreatic injury was histopathologically graded, and myeloperoxidase (MPO)-positive cells were counted. 5-HT3R mRNA was expressed in the pancreas. In acute pancreatitis model mice, amylase, lipase, and IL-6 levels were significantly increased in the blood. With ondansetron treatment, these levels were significantly decreased. Histopathological evaluation revealed that ondansetron attenuated the inflammatory damage in acute pancreatitis. The number of infiltrated neutrophils stained by MPO was decreased by ondansetron treatment. In summary, the 5-HT3R antagonist ondansetron attenuated pancreatic injury through its anti-inflammatory action. These findings suggest that ondansetron may potentially be of use for therapy of acute pancreatitis.

Combining isoflurane anesthesia with midazolam and butorphanol in rats.

Representative inhalant anesthetic agent, isoflurane is commonly used during surgery in rats. However, isoflurane mediates relatively strong respiratory depression. In human and veterinary medicine, sedatives and analgesics are co-administered to complement the anesthetic action of inhalant anesthesia. The present study aimed to establish the novel balanced anesthesia that combines midazolam and butorphanol with isoflurane (MBI) in rats. Male Sprague Dawley rats were divided into 2 groups, and administered either isoflurane monoanesthesia or isoflurane with midazolam (2.5 mg/kg, ip) and butorphanol (2.0 mg/kg, ip). The minimum alveolar concentration (MAC) in each group was evaluated. Induction and recovery times were measured in each group. Adverse reactions during induction were also recorded. In each group, vital signs were assessed for 1 h under 1.5×MAC of isoflurane. Instability of vital signs was assessed under each anesthesia by calculating coefficient of variance. Compared with isoflurane monoanesthesia, MBI anesthesia caused 32% MAC reduction (isoflurane monoanesthesia: 1.30 ± 0.09%, MBI 0.87 ± 0.08%, P<0.05). MB premedication mediated smooth sedating action with low incidence of adverse reactions such as urination and defecation. Isoflurane monoanesthsesia remarkably decreased respiratory rate and saturation O2 (SPO2). In contrast, MBI anesthesia resulted in a relatively stable respiratory rate without decreases in SPO2 during the anesthetic period. In summary, MB premedication is effective for attenuating respiratory depression induced by isoflurane, and achieving smooth induction. This anesthetic protocol serves as a novel option for appropriate anesthesia in rats.

Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor.

Valproic acid (VPA) is a widely used antiepileptic drug, which has recently been reported to modulate the neuronal differentiation of adipose tissue-derived stem cells (ASCs) in humans and dogs. However, controversy exists as to whether VPA really acts as an inducer of neuronal differentiation of ASCs. The present study aimed to elucidate the effect of VPA in neuronal differentiation of rat ASCs. One or three days of pretreatment with VPA (2 mM) followed by neuronal induction enhanced the ratio of immature neuron marker ßIII-tubulin-positive cells in a time-dependent manner, where the majority of cells also had a positive signal for neurofilament medium polypeptide (NEFM), a mature neuron marker. RT-PCR analysis revealed increases in the mRNA expression of microtubule-associated protein 2 (MAP2) and NEFM mature neuron markers, even without neuronal induction. Three-days pretreatment of VPA increased acetylation of histone H3 of ASCs as revealed by immunofluorescence staining. Chromatin immunoprecipitation assay also showed that the status of histone acetylation at H3K9 correlated with the gene expression of TUBB3 in ASCs by VPA. These results indicate that VPA significantly promotes the differentiation of rat ASCs into neuron-like cells through acetylation of histone H3, which suggests that VPA may serve as a useful tool for producing transplantable cells for future applications in clinical treatments.

Effect of midazolam and butorphanol premedication on inhalant isoflurane anesthesia in mice.

Isoflurane is a representative inhalant anesthesia used in laboratory animals. However, isoflurane mediates respiratory depression and adverse clinical reactions during induction. In the present study, we established a novel balanced anesthesia method in mice that combined isoflurane anesthesia with midazolam and butorphanol (MB). Thirty-four male C57BL/6J mice received either isoflurane alone or isoflurane with an intra-peritoneal MB premedication (3 mg/kg midazolam and 4 mg/kg butorphanol). The minimum alveolar concentration (MAC) in each group was evaluated. Induction time and adverse clinical reactions were recorded in each group. Core body temperature, heart rate, respiratory rate, and oxygen saturation (SPO(2)) were assessed before and for 1 h after induction. Premedication with MB achieved a significant reduction in MAC compared with isoflurane monoanesthesia (isoflurane, 1.38 ± 0.15%; isoflurane with MB, 0.78 ± 0.10%; P<0.05). Induction time was significantly shortened with MB premedication, and adverse reactions such as excitement or incontinence were observed less frequently. Furthermore, isoflurane anesthesia with MB premedication caused increase of respiratory rates compared to isoflurane monoanesthesia. No significant decrease of SPO(2) was observed in MBI anesthesia, while a decrease in SPO(2) was apparent with isoflurane monoanesthesia (baseline, 98.3% ± 1.1; 10 min after induction, 91.8 ± 6.4%; P<0.05). In conclusion, premedication with MB was effective for the mitigation of respiratory depression induced by isoflurane in mice, with rapid induction and fewer adverse clinical reactions.

Vital signs monitoring during injectable and inhalant anesthesia in mice.

Selecting the appropriate anesthetic protocol for the individual animal is an essential part of laboratory animal experimentation. The present study compared the characteristics of four anesthetic protocols in mice, focusing on the vital signs. Thirty-two male ddY mice were divided into four groups and administered anesthesia as follows: pentobarbital sodium monoanaesthesia; ketamine and xylazine combined (K/X); medetomidine, midazolam, and butorphanol combined (M/M/B); and isoflurane. In each group, rectal temperature, heart rate, respiratory rate, and O2 saturation (SPO2) were measured, and the changes over time and instability in these signs were compared. The anesthetic depth was also evaluated in each mouse, and the percentage of mice achieving surgical anesthesia was calculated. K/X anesthesia caused remarkable bradycardia, while the respiratory rate and SPO2 were higher than with the others, suggesting a relatively strong cardiac influence and less respiratory depression. The M/M/B group showed a relatively lower heart rate and SPO2, but these abnormalities were rapidly reversed by atipamezole administration. The pentobarbital group showed a lower SPO2, and 62.5% of mice did not reach a surgical anesthetic depth. The isoflurane group showed a marked decrease in respiratory rate compared with the injectable anesthetic groups. However, it had the most stable SPO2 among the groups, suggesting a higher tidal volume. The isoflurane group also showed the highest heart rate during anesthesia. In conclusion, the present study showed the cardiorespiratory characteristics of various anesthetic protocols, providing basic information for selecting an appropriate anesthetic for individual animals during experimentation.

Value of the 13C-urea breath test for detection of gastric Helicobacter spp. infection in dogs undergoing endoscopic examination.

Urea breath test (UBT) using an infrared spectral analyzer is widely used for non-invasive and rapid detection of gastric Helicobacter spp. in human, but not veterinary medicine. The main purposes of this study were to determine the reference range of the UBT in dogs and to evaluate its clinical usefulness. To address the first aim, 6 healthy laboratory beagles were subjected to UBT and upper gastrointestinal endoscopy. Gastric endoscopic biopsy samples from the antrum, corpus and fundus were examined for Helicobacter spp. by polymerase chain reaction (PCR) testing, rapid urease test (RUT), histology and cytology. Amoxicillin, metronidazole and omeprazole were given to infected dogs for 14 days, and dogs that became Helicobacter-negative were used to determine the reference range for UBT. To address the second aim, 32 canine patients underwent UBT before upper gastrointestinal endoscopy, and the sensitivity and specificity of UBT were calculated based on our newly determined reference range using PCR as the gold standard for detection of Helicobacter spp. Initially, all 6 laboratory beagles were infected in all gastric regions and became uninfected after eradication. The mean ± 2 SD UBT value after eradication was 0.6 ± 1.8‰, and the reference range for UBT was determined to be less than 2.5‰. UBT was completed successfully in 27 patients. Using our reference range, UBT displayed 89% (16/18) sensitivity and 89% (8/9) specificity, indicating that UBT was quite useful for the detection of gastric Helicobacter spp. infection in dogs.

Polypoid adenomas secondary to inflammatory colorectal polyps in 2 miniature dachshunds.

Two miniature dachshunds, a 7-year-old neutered male and an 8-year-old male, presented with chronic hematochezia and tenesmus. A solitary pedunculated or multiple diffuse colorectal polyps were identified by colonoscopy and resected by polypectomy. Inflammatory colorectal polyps (ICRPs) were diagnosed according to histopathological findings. Both cases were treated with immunosuppressive therapy, and the clinical signs were resolved, although the colorectal polyps remained to some extent. Several months after the initial diagnosis, both cases presented with recurrence of hematochezia and enlargement of the polyps. A second colonoscopic polypectomy was performed, and adenoma was diagnosed histopathologically in both cases. ICRPs are a nonneoplastic disease, but their long-term prognosis is unknown. Careful follow-up seems to be important, and repetitive biopsy is recommended when growth of polyps is identified in miniature dachshunds with ICRPs.

Factors Related to Regulatory Approval of Late-Stage Development Compounds: Analysis of Japanese Pharmaceutical Company Activities, 1995-2007.

Japanese pharmaceutical companies invest resources in their internal research and development (R&D) activities and in-licensing activities especially from Western companies, for the local market. The objective of this research is to investigate the fate of late-stage compounds developed by them and to identify company profiles and compound characteristics that could relate to regulatory approvability. Using publicly available information for late-stage compounds that were developed by Japanese companies in 1995-2007, logistic regression analysis was conducted to investigate the company characteristics and regulatory approval ratio, as well as compound characteristics and probability of approval, for late-stage development compounds. Compound approvability was correlated to the time when the compound was developed (ie, the approval ratio of compounds in phase 3 or later in 1995-1998 was lower than that in 2001 or later); also, in-licensed compounds from large pharmaceutical companies received a higher approval ratio. Company size and R&D expenses were not correlated to their approval ratio.

Mucosal imbalance of interleukin-1ß and interleukin-1 receptor antagonist in canine inflammatory bowel disease.

Interleukin (IL)-1ß is a key mediator of the inflammatory response. IL-1 receptor antagonist (IL-1Ra) regulates inflammation by functioning as an endogenous inhibitor of IL-1ß. A disruption of the balance between IL-1ß and IL-1Ra has been identified in human inflammatory bowel disease (IBD). The objective of this study was to determine whether there is an intestinal imbalance of IL-1ß and IL-1Ra in canine IBD by comparing expression of IL-1ß and IL-1Ra mRNA by real-time RT-PCR and expression of IL-1ß and IL-1Ra protein by ELISA in 21 dogs with IBD, 15 dogs with intestinal lymphoma ('inflammatory' controls) and 20 healthy Beagles ('healthy' controls). A significant decrease in the intestinal IL-1Ra:IL-1ß ratio of mRNA and protein was observed in IBD cases when compared with healthy control dogs. In contrast, a decrease in IL-1Ra:IL-1ß ratio was not observed in dogs with intestinal lymphoma. The IL-1Ra:IL-1ß protein ratio was negatively correlated with clinical severity in dogs with IBD. An intestinal imbalance between IL-1ß and IL-1Ra production may play a role in the pathogenesis of canine IBD.

Effect of mosapride on prednisolone-induced gastric mucosal injury and gastric-emptying disorder in dog.

Previous report demonstrated that prokinetic agent mosapride has anti-ulcerogenic action in rat-indomethacin gastric mucosal injury model. Here, we assessed the prophylactic effect of mosapride on gastric mucosal injury and emptying disorder induced by prednisolone in dogs. Crossover study design was employed. Six healthy beagles were administered prednisolone alone (2 mg/kg, twice a day [BID] subcutaneously) and prednisolone with mosapride (1 mg/kg, BID, orally), followed by an interval of at least 6 weeks. In each treatment, gastric mucosal injury was scored endoscopically according to the modified Lanza scale, and gastric emptying was assessed with (13)C-octanoic acid breath test. The incidence of gastrointestinal adverse events was also investigated. Coadministration of mosapride with prednisolone significantly (P<0.05) reduced the gastric mucosal injury score (mean ± SD, 17.67 ± 6.96), compared with that of prednisolone treatment alone (25.50 ± 13.03). Prednisolone treatment delayed the half-emptying time (184 ± 45 min) compared with that of controls (137 ± 19 min), and coadministration of mosapride improved this gastric-emptying delay (143 ± 29 min). Furthermore, the incidence of the gastrointestinal adverse event vomiting became less frequent upon coadministration with mosapride. In addition to its prokinetic action, our study suggests that mosapride has an anti-ulcerogenic action in dogs. The use of mosapride in combination with prednisolone is effective for attenuating prednisolone-induced gastrointestinal adverse events.

Molecular cloning and expression analysis of the canine chemokine receptor CCR9.

The chemokine receptor CCR9, which interacts with the thymus-expressed chemokine TECK/CCL25, contributes to the localization of lymphocytes to the small intestine, and is implicated in the development of human inflammatory bowel disease (IBD); however, their role in canine IBD is unknown. The objective of this study was to isolate cDNA encoding CCR9 and to investigate CCR9 expression in normal canine tissues and lymphoid cell lines. The complete open reading frame contained 1104 bp, encoding 367 amino acids, with 85% and 81% identity to human and mouse homologs, respectively. CCR9 mRNA was detected in all tissues investigated with the highest expression level in the small intestine. CCR9 mRNA was also expressed in GL-1, a canine B cell leukemia cell line, but not in CLBL-1, a canine B cell lymphoma cell line. Immunoblot and flow cytometry analyses of these cell lines using an anti-human CCR9 monoclonal antibody revealed that CCR9 protein expression was detected only in GL-1, indicating the cross-reactivity of the antibody. Using the antibody, flow cytometry showed that the proportions of CCR9(+) cells were small (mean, 4.88%; SD, 2.15%) in the normal canine PBMCs. This study will be useful in understanding canine intestinal immunity and the immunopathogenesis of canine IBD.

Molecular cloning and characterization of canine fractalkine and its receptor CX3CR1.

Fractalkine, also known as CX(3)CL1, is a unique chemokine that mediates inflammatory responses and is involved in the pathogenesis of several inflammatory disorders, including inflammatory bowel disease (IBD) in humans. In this study, we isolated cDNAs encoding canine fractalkine and its receptor CX(3)CR1, and assessed the biological activity of these molecules. The deduced amino acid sequence of the canine fractalkine cDNA showed 66% and 57% identity to human and mouse homologs, respectively. The N-terminal chemokine domain of the canine fractalkine showed 68% and 65% identity to human and mouse counterparts, respectively. The canine CX(3)CR1 amino acid sequence showed close homology to its human (83% identity) and mouse (81% identity) counterparts. Fractalkine and CX(3)CR1 mRNA were detected in all tissues in this study. Relatively higher expression levels of fractalkine mRNA were observed in the brain, medulla spinalis, small intestine, and mesenteric lymph nodes (MLNs), whereas higher expression levels of CX(3)CR1 mRNA were observed in the medulla spinalis, brain, liver, small intestine, and MLNs. The cross-reactivities of anti-human fractalkine antibody and anti-rat CX(3)CR1 antibody to canine proteins were confirmed using recombinant canine fractalkine and a cell line overexpressing canine CX(3)CR1, respectively. A transwell chemotaxis assay showed that the recombinant canine fractalkine induced migration in canine lymphoid cells expressing CX(3)CR1. The present study will be useful in understanding the canine immune system and the immunopathogenesis of canine inflammatory diseases.

Decreased gallbladder emptying in dogs with biliary sludge or gallbladder mucocele.

Biliary sludge in dogs is dismissed commonly as an incidental finding. On the other hand, gallbladder mucocele is reported increasingly in dogs and can lead to biliary obstruction or gallbladder rupture. Cholestasis is suspected to play a role in development of sludge and mucoceles, though there are no data in dogs to support this. We investigated gallbladder emptying, a key factor in biliary flow, in dogs with mobile sludge, immobile sludge, or gallbladder mucocele and in healthy controls. Gallbladder ejection fraction estimated by ultrasonography was used as the index of gallbladder emptying. The ejection fraction at 60 min after eating was significantly decreased in all three abnormal groups. Moreover, all dogs with sludge or a mucocele had gallbladder distension. These changes were the greatest in the mucocele group. Thus, biliary stasis occurs not only in dogs with gallbladder mucocele but also in dogs with biliary sludge. Cholestasis may play a role in the pathogenesis or progression of these diseases in dogs.