Clozapine attenuates mitochondrial burdens and abnormal behaviors elicited by phencyclidine in mice via inhibition of p47 phox; Possible involvements of phosphoinositide 3-kinase/Akt signaling.

BACKGROUND: Oxidative stress and mitochondrial dysfunction have been implicated in the pathophysiology of schizophrenia. AIMS: We investigated whether antipsychotic clozapine modulates nicotinamide adenine dinucleotide phosphate oxidase and mitochondrial burdens induced by phencyclidine in mice. METHODS: We examined the effect of clozapine on nicotinamide adenine dinucleotide phosphate oxidase activation, mitochondrial burdens (i.e. oxidative stress and mitochondrial dysfunction), and activities of enzymatic antioxidant in the prefrontal cortex, and subsequent abnormal behaviors induced by repeated treatment with phencyclidine. p47 phox Knockout mice and LY294002, a phosphoinositide 3-kinase inhibitor, were employed to elucidate the pharmacological mechanism of clozapine. RESULTS: Phencyclidine treatment resulted in an early increase nicotinamide adenine dinucleotide phosphate oxidase activity, membrane translocation of p47 phox, interaction between p-Akt and p47 phox, and mitochondrial burdens in wild-type mice. Although these increases returned to near control level four days post-phencyclidine, mitochondrial superoxide dismutase and glutathione peroxidase activities were decreased at that time. Clozapine, LY294002, or p47 phox knockout significantly ameliorated social withdrawal and recognition memory deficits produced by phencyclidine. Importantly, LY294002 did not significantly alter the effects of clozapine against abnormal behaviors and the interaction between p-Akt and p47 phox induced by phencyclidine. Furthermore, neither LY294002 nor clozapine exhibited any additive effects to the protection afforded by p47 phox knockout against phencyclidine insult. CONCLUSION: Our results suggest that p47 phox gene mediates phencyclidine-induced mitochondrial burdens and abnormal behaviors, and that the interactive modulation between p47 phox and phosphoinositide 3-kinase/Akt is important for the understanding on the pharmacological mechanism of clozapine.

HEMATOLOGIC AND PLASMA BIOCHEMICAL VALUES OF CINEREOUS VULTURE (AEGYPIUS MONACHUS).

The aim of this study was to establish hematologic and plasma biochemical reference intervals for clinically healthy cinereous vultures ( Aegypius monachus ) in a rehabilitation setting before release. Animals used in this study were cinereous vultures hospitalized in a wildlife center located in the province of Gyeongsangnam-do, the Republic of Korea. Blood samples were collected from 31 cinereous vultures before their release between 2011 and 2014 at the Gyeongnam Wildlife Center. Complete blood count and plasma biochemical analyses were performed within 2 hr of the blood sampling. Reference intervals were calculated from the 10th to the 90th percentile, together with the mean, SD, and lowest and highest observed values. The results of this study may be useful in evaluating the physical condition and clinical monitoring of cinereous vultures in captivity before release and contribute to the determination of reference ranges for healthy cinereous vultures.

LAPAROSCOPIC OVARIECTOMY IN THE ASIATIC BLACK BEAR (URSUS THIBETANUS) WITH THE USE OF THE SONICISION™ DEVICE.

Laparoscopic ovariectomy was performed in two Asiatic black bears ( Ursus thibetanus ). Bears were placed in a 20° Trendelenburg position on a surgical table. A three-portal technique was used. A camera port was established 10 cm caudal to the umbilicus with a 5-mm cannula. Two instrument ports were made 1 cm caudal to the umbilicus with a 5-mm cannula and 8 cm caudal to the camera port with a 12-mm cannula, respectively. The suspensory ligament, ovarian vasculature, and uterine horn tip were progressively dissected following coagulation with the Sonicision™ cordless ultrasonic dissection device. The resected ovary was exteriorized through the 12-mm instrument portal site but enlarged to a 2-cm incision length. The abdominal musculature, subcutaneous tissue, and skin of the portal sites were closed separately. Total surgical time was 113 min (Bear A) and 49 min (Bear B), and no postoperative complications were encountered. This is the first report of laparoscopic ovariectomy in the Asiatic black bear.

Comparison of oblique coronal images in knee of three-dimensional isotropic T2-weighted turbo spin echo MRI versus two-dimensional fast spin echo T2-weighted sequences for evaluation of posterior cruciate ligament injury.

OBJECTIVE: To compare image quality between three-dimensional volume isotropic turbo spin echo acquisition (3D VISTA) with the posterior cruciate ligament (PCL) view and two-dimensional (2D) fast spin echo (FSE) for evaluation of PCL injury. METHODS: This retrospective study included 60 patients with clinical suspicion of PCL injury who underwent both 2D FSE and 3D VISTA of the knee between January 2015 and December 2015. The diagnostic performance of each oblique coronal view and the combined images was evaluated for sensitivity, specificity and accuracy for diagnosing a PCL tear. The arthroscopically confirmed diagnoses were used as the reference standard. Data were analyzed using the McNemar test. RESULTS: The mean contrast-to-noise ratio was significantly higher for 3D VISTA than for 2D FSE. The two imaging modalities did not differ significantly in anatomical identification ability, with the exception of margin sharpness, which was inferior for 3D VISTA with Reader 2 (p = 0.038). When we classified the diagnoses of PCL injury as normal or abnormal, there were no significant differences in sensitivity, specificity or accuracy between the PCL view of 3D VISTA and 2D FSE images (p > 0.05). CONCLUSION: 3D VISTA had a superior contrast-to-noise ratio than 2D FSE and similar image quality in the evaluation of the PCL. The PCL view of 3D VISTA has the same diagnostic ability as 2D FSE in the diagnosis of PCL injury and can thus replace 2D FSE. Advances in knowledge: The oblique coronal view 3D VISTA MRI has similar diagnostic ability to 2D FSE in the diagnosis of PCL injury, and therefore 3D VISTA image can replace 2D FSE.

Unilateral laparoscopic ovariectomy in a red fox (Vulpes vulpes) with an ovarian cyst.

Unilateral laparoscopic ovariectomy was attempted in a red fox (Vulpes vulpes) with an ovarian cyst through single portal access. The ovarian cyst was resistant to conservative therapy using gonadotropin-releasing hormone. A 10-mm laparoscope with an operating channel was introduced into the abdomen via a 12-mm umbilical portal. The left ovary and cyst (34.1 x 30.8 mm) were fixed to the left abdominal wall by a transabdominal suspension suture. The ovarian pedicles and ligaments were progressively cauterized and transected with a multifunction bipolar electrocoagulation forceps. The resected cystic ovary was exteriorized through the umbilical portal site. The surgical time was 42 min, and no intra- and postoperative complications were encountered. Two months after the surgery mating was observed, and the fox gave birth to three healthy cubs 56 days after the mating. This is the first report of using laparoscopy in the red fox with an ovarian cyst.

Oncogenic potential of CK2α and its regulatory role in EGF-induced HDAC2 expression in human liver cancer.

Histone deacetylase 2 (HDAC2) is aberrantly regulated and plays a pivotal role in the development of hepatocellular carcinoma (HCC) through regulation of cell-cycle components at the transcriptional level, but the underlying mechanism leading to oncogenic HDAC2 remains unknown. In this study, we show that expression of CK2α (casein kinase II α subunit) was up-regulated in a large cohort of human HCC patients, and that high expression of CK2α was significantly associated with poor prognosis of HCC patients in terms of five-year overall survival. It was also found that CK2α over-expression positively correlated with HDAC2 over-expression in a subset of HCCs. We observed that treatment with epidermal growth factor (EGF) elicited an increase in CK2α expression and Akt phosphorylation, causing induction of HDAC2 expression in liver cancer cells. It was also observed that ectopic expression of dominant-negative CK2α blocked EGF-induced HDAC2 expression, and that ectopic CK2α expression attenuated the suppressive effect of Akt knockdown on HDAC2 expression in liver cancer cells. Targeted disruption of CK2α influenced the cell cycle, causing a significant increase in the number of liver cancer cells remaining in G2/M phase, and suppressed growth via repression of Cdc25c and cyclin B in liver cancer cells. Taken together, our findings suggest the oncogenic potential of CK2α in liver tumorigenesis. Furthermore, a regulatory mechanism for HDAC2 expression is proposed whereby EGF induces transcriptional activation of HDAC2 by CK2α/Akt activation in liver cancer cells. Therefore, this makes CK2α a promising target in cancer therapy.

Laparoscopic nephrectomy in dogs: an initial experience of 16 experimental procedures.

Left laparoscopic nephrectomy was performed in 16 dogs to describe the surgical techniques and initial experiences associated with operation time and surgery complications. The renal vein and artery were occluded by three ligating clips, respectively, and the ureter was sectioned after ligation with ligating clips at the level of the iliac vessels. A morcellation technique was used to remove the kidney from the abdominal cavity after placing it into a specimen retrieval bag. Total operation time and time spent for each different surgical stage in the first five operations were compared with those in the last five of the 16 operations. The factors that affected the differences of total operation time were examined, including sex, bodyweight, number of operations, incision length, and surgical stages. Six intra-operative complications occurred including splenic hemorrhage (3 cases), torn specimen retrieval bag during kidney morcellation (1 case), and subcutaneous emphysema (2 cases). Surgical time for laparoscopic nephrectomy was affected primarily by the time spent for renal vascular pedicle section and could be decreased as the number of cases increased. Thus, laparoscopic nephrectomy using ligating clips and morcellation for kidney removal could be considered where nephrectomy is indicated in dogs.

Differences between vocalization evoked by social stimuli in feral cats and house cats.

To investigate how socialization can affect the types and characteristics of vocalization produced by cats, feral cats (n=25) and house cats (n=13) were used as subjects, allowing a comparison between cats socialized to people and non-socialized cats. To record vocalization and assess the cats' responses to behavioural stimuli, five test situations were used: approach by a familiar caretaker, by a threatening stranger, by a large doll, by a stranger with a dog and by a stranger with a cat. Feral cats showed extremely aggressive and defensive behaviour in most test situations, and produced higher call rates than those of house cats in the test situations, which could be attributed to less socialization to other animals and to more sensitivity to fearful situations. Differences were observed in the acoustic parameters of feral cats in comparison to those of house cats. The feral cat produced significantly higher frequency in fundamental frequency, peak frequency, 1st quartile frequency, 3rd quartile frequency of growls and hisses in agonistic test situations. In contrast to the growls and hisses, in meow, all acoustic parameters like fundamental frequency, first formant, peak frequency, 1st quartile frequency, and 3rd quartile frequency of house cats were of significantly higher frequency than those of feral cats. Also, house cats produced calls of significantly shorter in duration than feral cats in agonistic test situations. These results support the conclusion that a lack of socialization may affect usage of types of vocalizations, and the vocal characteristics, so that the proper socialization of cat may be essential to be a suitable companion house cat.