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Meloxicam, a preferential COX-2 inhibitor, is a commonly used NSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long-term meloxicam treatment on growing pigs were studied. Twelve piglets (n=6 receiving daily meloxicam 0.4 mg/kg orally from 48 until 110 days of age; n=6 receiving only applesauce (vehicle control)) were subjected to visual and objective gait analysis by pressure plate measurements at several time points. Following euthanasia a complete postmortem examination was performed and samples of the talus and distal tibia, including the distal physis, were collected. Trabecular bone microarchitecture was analysed by microCT scanning, bone stiffness by compression testing and growth plate morphology using light microscopy. Animals were not lame and gait patterns did not differ between the groups. Pathological examination revealed no lesions compatible with known side effects of NSAIDs. Trabecular bone microarchitecture and growth plate morphology did not differ between the two groups. The findings of this in vivo study reduce concerns regarding the long-term use of meloxicam in young, growing piglets., Competing Interests: Competing interests: None declared., (© British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Diagnostic imaging is one of the pillars in the clinical workup of horses with clinical signs of cervical spinal disease. An improved awareness of morphologic variations in equine cervical vertebrae would be helpful for interpreting findings. The aim of this anatomic study was to describe CT variations in left-right symmetry and morphology of the cervical and cervicothoracic vertebrae in a sample of horses. Postmortem CT examinations of the cervical spine for horses without congenital growth disorders were prospectively and retrospectively recruited. A total of 78 horses (27 foals, 51 mature horses) were evaluated. Twenty-six horses (33.3%) had homologous changes in which a transposition of the caudal part of the transverse process (caudal ventral tubercle) of C6 toward the ventral aspect of the transverse process of C7 was present (n = 10 bilateral, n = 12 unilateral left-sided, n = 4 unilateral right-sided). There was one horse with occipito-atlantal malformation, two horses with rudimentary first ribs bilaterally, and one horse with bilateral transverse processes at Th1, representing homeotic (transitional) vertebral changes. Chi-square tests identified no significant differences in the number of conformational variations between the group of mature horses with or without clinical signs (P = 0.81) or between the group of mature horses and the group of foals (P = 0.72). Findings indicated that, in this sample of horses, the most frequently identified variations were homologous variations (transposition of the caudal part of the transverse process of C6-C7) in the caudal equine cervical vertebral column. Homeotic (transitional) variations at the cervicothoracic vertebral column were less common., (© 2016 American College of Veterinary Radiology.)

Cell fate decisions and pluripotency, but also malignancy depend on networks of key transcriptional regulators. The T-box transcription factor TBX3 has been implicated in the regulation of embryonic stem cell self-renewal and cardiogenesis. We have recently discovered that forced TBX3 expression in embryonic stem cells promotes mesendoderm specification directly by activating key lineage specification factors and indirectly by enhancing paracrine NODAL signalling. Interestingly, aberrant TBX3 expression is associated with breast cancer and melanoma formation. In other cancers, loss of TBX3 expression is associated with a more aggressive phenotype e.g. in gastric and cervical cancer. The precise function of TBX3 in pancreatic ductal adenocarcinoma remains to be determined. In the current study we provide conclusive evidence for TBX3 overexpression in pancreatic cancer samples as compared to healthy tissue. While proliferation remains unaltered, forced TBX3 expression strongly increases migration and invasion, but also angiogenesis in vitro and in vivo. Finally, we describe the TBX3-dependency of cancer stem cells that perpetuate themselves through an autocrine TBX3-ACTIVIN/NODAL signalling loop to sustain stemness. Thus, TBX3 is a new key player among pluripotency-related genes driving cancer formation., (Copyright © 2016 Helmholtz Zentrum München. Published by Elsevier B.V. All rights reserved.)

Background: Myxoma is a very rare benign cardiac tumor in dogs. This is the first description of a cardiac myxoma originating from the left ventricular outflow tract, presumably causing sudden death., Case Presentation: A previously healthy 12-year-old male West Highland white terrier was found dead during its 1-week stay in a kennel. The dog was known to have a cardiac murmur. On necropsy, a pedunculated neoplasia was found attached to the interventricular aspect of the left ventricular outflow tract, resulting in almost complete obstruction of the aorta. As this was the only abnormality identified, the tumor was considered as the cause of sudden death. Histopathologic findings were compatible with a myxoma., Conclusions: Benign intraluminal tumors of the heart are very rare in dogs, but may have fatal consequences. Echocardiography could have revealed the cause of the cardiac murmur of this previously asymptomatic dog. Surgical removal could have been possible, as the tumor was pedunculated.

Pluripotency represents a cell state comprising a fine-tuned pattern of transcription factor activity required for embryonic stem cell (ESC) self-renewal. TBX3 is the earliest expressed member of the T-box transcription factor family and is involved in maintenance and induction of pluripotency. Hence, TBX3 is believed to be a key member of the pluripotency circuitry, with loss of TBX3 coinciding with loss of pluripotency. We report a dynamic expression of TBX3 in vitro and in vivo using genetic reporter tools tracking TBX3 expression in mouse ESCs (mESCs). Low TBX3 levels are associated with reduced pluripotency, resembling the more mature epiblast. Notably, TBX3-low cells maintain the intrinsic capability to switch to a TBX3-high state and vice versa. Additionally, we show TBX3 to be dispensable for induction and maintenance of naive pluripotency as well as for germ cell development. These data highlight novel facets of TBX3 action in mESCs., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

The protein kinase D isoenzymes PKD1/2/3 are prominent downstream targets of PKCs (Protein Kinase Cs) and phospholipase D in various biological systems. Recently, we identified PKD isoforms as novel mediators of tumour cell-endothelial cell communication, tumour cell motility and metastasis. Although PKD isoforms have been implicated in physiological/tumour angiogenesis, a role of PKDs during embryonic development, vasculogenesis and angiogenesis still remains elusive. We investigated the role of PKDs in germ layer segregation and subsequent vasculogenesis and angiogenesis using mouse embryonic stem cells (ESCs). We show that mouse ESCs predominantly express PKD2 followed by PKD3 while PKD1 displays negligible levels. Furthermore, we demonstrate that PKD2 is specifically phosphorylated/activated at the time of germ layer segregation. Time-restricted PKD2-activation limits mesendoderm formation and subsequent cardiovasculogenesis during early differentiation while leading to branching angiogenesis during late differentiation. In line, PKD2 loss-of-function analyses showed induction of mesendodermal differentiation in expense of the neuroectodermal germ layer. Our in vivo findings demonstrate that embryoid bodies transplanted on chicken chorioallantoic membrane induced an angiogenic response indicating that timed overexpression of PKD2 from day 4 onwards leads to augmented angiogenesis in differentiating ESCs. Taken together, our results describe novel and time-dependent facets of PKD2 during early cell fate determination.

Knowledge about the effects of the neuropeptide oxytocin (OXT) on human sexual behaviors and partner interactions remains limited. Based on our previous studies, we hypothesize that OXT should be able to positively influence parameters of sexual function and couple interactions. Employing a naturalistic setting involving 29 healthy heterosexual couples (n=58 participants), we analyzed the acute effects of intranasally administered OXT (24IU) on sexual drive, arousal, orgasm and refractory aspects of sexual behavior together with partner interactions. Data were assessed by psychometric instruments (Acute Sexual Experiences Scale, Arizona Sexual Experience Scale) as well as biomarkers, such as cortisol, α-amylase and heart rate. Intranasal OXT administration did not alter "classical" parameters of sexual function, such as sexual drive, arousal or penile erection and lubrication. However, analysis of variance and a hierarchical linear model (HLM) revealed specific effects related to the orgasmic/post-orgasmic interval as well as parameters of partner interactions. According to HLM analysis, OXT increased the intensity of orgasm, contentment after sexual intercourse and the effect of study participation. According to ANOVA analysis, these effects were more pronounced in men. Men additionally indicated higher levels of sexual satiety after sexual intercourse with OXT administration. Women felt more relaxed and subgroups indicated better abilities to share sexual desires or to empathize with their partners. The effect sizes were small to moderate. Biomarkers indicated moderate psychophysiological activation but were not affected by OXT, gender or method of contraception. Using a naturalistic setting, intranasal OXT administration in couples exerted differential effects on parameters of sexual function and partner interactions. These results warrant further investigations, including subjects with sexual and relationship problems., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Severe acute pancreatitis is still a potentially life threatening disease with high mortality. The aim of this study was to evaluate the therapeutic effect of thoracic epidural anaesthesia (TEA) on survival, microcirculation, tissue oxygenation and histopathologic damage in an experimental animal model of severe acute pancreatitis in a prospective animal study., Methods: In this study, 34 pigs were randomly assigned into 2 treatment groups. After severe acute pancreatitis was induced by intraductal injection of glycodesoxycholic acid in Group 1 (n = 17) bupivacaine (0.5%; bolus injection 2 ml, continuous infusion 4 ml/h) was applied via TEA. In Group 2 (n = 17) no TEA was applied. During a period of 6 hours after induction, tissue oxygen tension (tpO2) in the pancreas and pancreatic microcirculation was assessed. Thereafter animals were observed for 7 days followed by sacrification and histopathologic examination., Results: Survival rate after 7 days was 82% in Group 1 (TEA) versus 29% in Group 2: (Control) (P <0.05). Group 1 (TEA) also showed a significantly superior microcirculation (1,608 ± 374 AU versus 1,121 ± 510 AU; P <0.05) and tissue oxygenation (215 ± 64 mmHg versus 138 ± 90 mmHG; P <0.05) as compared to Group 2 (Control). Consecutively, tissue damage in Group 1 was reduced in the histopathologic scoring (5.5 (3 to 8) versus 8 (5.5 to 10); P <0.05)., Conclusions: TEA led to improved survival, enhanced microcirculatory perfusion and tissue oxygenation and resulted in less histopathologic tissue-damage in an experimental animal model of severe acute pancreatitis.

A total of 97 patients with an acute monoradicular lumbosacral compression syndrome and a herniated disc at the same level were reinvestigated an average of 25 months after the acute event. Assessment was based on CT investigation and "root score", which was compiled from reports of subjective complaints and neurological deficits. All patients had initially undergone conservative treatment as inpatients. At the time of reinvestigation CT examination of the herniated discs revealed that they were unchanged in 56.7%, some-what smaller in 34%, no longer visible in 4.1% and larger in 5.2%. Nevertheless, 53.6% of patients were free of complaints, while 23.7% had improved clinically by more then 75%. The remainder showed improvement by about 25-75%. In no patient was the score unchanged or worse. In 69% of the patients neurological deficits were no longer demonstrable, and the remaining patients were not aware of deficits or did not feel any impairment from deficits that were obvious on clinical example. In 22.7% impairment was caused solely by local radicular or pseudoradicular pain. From these results it can be concluded that herniation of the disc precipitates the acute event but is not the sole source of the pain. In the majority of cases, during the further course of the disease the herniated disc causes no pain. It appears, therefore, that the course of disease following a disc herniation can be influenced very favourably by non-operative treatment and that in more than 50% of cases the condition becomes clinically silent. It follows that in neuroradicular compression syndromes a neurological deficit associated with the acute event does not mean operative intervention is indicated.

Rupture of the spleen occurred in five patients (aged 44-59 years) in the course of chronic or chronic recurrent pancreatitis. In three patients the rupture was a consequence of perisplenic adhesions associated with subclinical chronic pancreatitis, in another there was direct enzymatic erosion of the splenic capsule via the phrenicosplenic ligament, and in the fifth patient haemorrhagic infarction followed splenic venous thrombosis. In four patient there was a history of chronic pancreatitis related to alcohol abuse. On admission all patients complained of breathing-related pains radiating into the shoulder. Three patients also had abnormal radiological signs in the left lower lung field (high diaphragm, effusion, infiltration). The findings can be explained pathogenetically by infiltration of the phrenicosplenic ligament which connects the tail of the pancreas with the splenic hilus and the diaphragm. The final diagnostic confirmation and indication for surgery was in all cases made by computed tomography. This is thus the imaging procedure of choice if splenic involvement is suspected in the course of chronic pancreatitis.

Oxidation of erythrocyte membrane SH-groups and concomitant cross-linking of spectrin, which induce a partial loss of phospholipid asymmetry (Haest, C.W.M., Plasa, G., Kamp, D. and Deuticke, B. (1978) Biochim. Biophys. Acta 509, 21-32) are now shown to result in a remarkable increase of the rates of transbilayer reorientation of exogenously incorporated lysophospholipids. Reorientation of both, neutral lysophosphatidylcholine and of negatively charged lysophosphatidylserine is enhanced. A decrease of the activation energy of the reorientation process as well as quantitative changes of the dependence of reorientation on the lysophosphatidylcholine and cholesterol content of the membrane indicate formation of new reorientation sites or modification of existing sites. A common mechanism may underly the formation of reorientation sites and the occurrence of leaks for small solutes (Deuticke, B., Poser, B., Lütkemeier, P. and Haest, C.W.M. (1983) Biochim. Biophys. Acta 731, 196-210) subsequent to oxidation of membrane SH-groups. Whereas exogenous lysophospholipids completely equilibrate between the two lipid layers regardless of the extent of oxidation of SH-groups, endogenous inner layer phospholipids become available for reorientation in a graded way. Native phospholipid asymmetry is therefore not the result of a low transbilayer mobility of phospholipids, but probably due to a lack of access of inner layer phospholipids to the reorientation sites.

Labelled lysophospholipids were inserted into the outer layer of the erythrocyte membrane and their reorientation (flip) to the inner layer quantified by following the increase of the fraction of lysophospholipids not extractable by albumin. Flip rate constants were calculated from the kinetics of equilibration of the lysophospholipids between two compartments, the outer and the inner leaf of the bilayer, in the early phase of the flip kinetics where correction for non-enzymatic hydrolysis and acylation could be omitted. The distribution of a lysophospholipid finally attained reflects its affinity for the two layers. Whereas lysophosphatidylcholine has a slight preference for the outer layer of the membrane, lysophosphatidylserine spontaneously concentrates in the inner layer up to a ratio of 4:1. This asymmetry mimics the distribution of phosphatidylserine in the native membrane. Flip rates depend on membrane lipid compositions. They are enhanced by cholesterol depletion. Comparison of various mammalian species demonstrates that erythrocytes with a higher phosphatidylcholine/sphingomyelin ratio and high content of polyunsaturated fatty acids (mouse and rat) have a high transbilayer mobility, in contrast to erythrocytes with a low phosphatidylcholine/sphingomyelin ratio and a low content of polyunsaturated fatty acids (ox). Molecular properties of lysophospholipids influence their transbilayer mobility. Flip rates of lysophospholipids are enhanced not only by unsaturation of their fatty acid, but also by a negative net charge on the headgroup. This indicates that the strongly asymmetric distribution of phosphatidylserine in the native erythrocyte membrane, which is maintained for the lifespan of the cell, does not result from a lack of transbilayer mobility.

The alimentary tract is frequently used as a hiding place for the transportation of drugs. We report on the cases of two smugglers with drug packages ("body packing") in the gastrointestinal tract. Radiological techniques provide the best method of diagnosis. The clinical problems and symptoms of acute drug intoxication are presented.