Existence of bovine neonatal pancytopenia before the year 2005? Retrospective evaluation of 215 cases of haemorrhagic diathesis in cattle.

Haemorrhagic diathesis (HD) in cattle is a relatively rare syndrome that can have many different causes. With the occurrence of bovine neonatal pancytopenia (BNP) in 2007, the number of cases of HD in cattle has increased. This led to an enhanced interest in diseases presenting with bleeding disorders. The possible causes of HD in cattle, the clinical findings, and the course of various diseases are described and evaluated. Furthermore, we determined whether cases of BNP occurred before the introduction of the vaccine Pregsure BVD since its widespread use was associated with the syndrome. Records of 215 cases of HD in cattle that had been referred to the Clinic for Ruminants with Ambulatory and Herd Health Services at the Centre for Clinical Veterinary Medicine, Ludwig Maximilian University, Munich, between 1982 and 2014 were evaluated. The two most commonly diagnosed diseases were BNP (n = 95) and septicaemia (n = 35), with fatality rates of 82% and 66%, respectively. In 27 (13%) cases, no clear cause for the HD could be designated. Statistically significant differences were found with regard to the course of the various disorders and the clinical findings. A receiver operating characteristic analysis of thrombocyte counts of affected animals at the time of arrival at the clinic did not provide any predictive information on disease outcome. Two cases of HD occurred before the introduction of Pregsure BVD (1989, 1991). In both cases, clinical, haematological, and pathological findings were identical to BNP. The cause of HD in these two cases could not be determined retrospectively.

The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour.

Neuropeptide Y (NPY), one of the most abundant peptides in the nervous system, exerts its effects via five receptor types, termed Y1, Y2, Y4, Y5 and Y6. NPY's pleiotropic functions comprise the regulation of brain activity, mood, stress coping, ingestion, digestion, metabolism, vascular and immune function. Nerve-derived NPY directly affects immune cells while NPY also acts as a paracrine and autocrine immune mediator, because immune cells themselves are capable of producing and releasing NPY. NPY is able to induce immune activation or suppression, depending on a myriad of factors such as the Y receptors activated and cell types involved. There is an intricate relationship between psychological stress, mood disorders and the immune system. While stress represents a risk factor for the development of mood disorders, it exhibits diverse actions on the immune system as well. Conversely, inflammation is regarded as an internal stressor and is increasingly recognized to contribute to the pathogenesis of mood and metabolic disorders. Intriguingly, the cerebral NPY system has been found to protect against distinct disturbances in response to immune challenge, attenuating the sickness response and preventing the development of depression. Thus, NPY plays an important homeostatic role in balancing disturbances of physiological systems caused by peripheral immune challenge. This implication is particularly evident in the brain in which NPY counteracts the negative impact of immune challenge on mood, emotional processing and stress resilience. NPY thus acts as a unique signalling molecule in the interaction of the immune system with the brain in health and disease.

The GPR55 antagonist CID16020046 protects against intestinal inflammation.

BACKGROUND: G protein-coupled receptor 55 (GPR55) is a lysophospholipid receptor responsive to certain cannabinoids. The role of GPR55 in inflammatory processes of the gut is largely unknown. Using the recently characterized GPR55 inhibitor CID16020046, we determined the role of GPR55 in experimental intestinal inflammation and explored possible mechanisms of action. METHODS: Colitis was induced by either 2.5% dextran sulfate sodium (DSS) supplemented in the drinking water of C57BL/6 mice or by a single intrarectal application of trinitrobenzene sulfonic acid (TNBS). KEY RESULTS: Daily application of CID16020046 (20 mg/kg) significantly reduced inflammation scores and myeloperoxidase (MPO) activity. In the DSS colitis model, levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß), and the expression of cyclooxygenase (Cox)-2 and signal transducer and activator of transcription 3 (STAT-3) were reduced in colon tissues while in TNBS-induced colitis, levels of Cox-2, IL-1ß and IL-6 were significantly lowered. Evaluation of leukocyte recruitment by flow cytometry indicated reduced presence of lymphocytes and macrophages in the colon following GPR55 inhibition in DSS-induced colitis. In J774A.1 mouse macrophages, inhibition of GPR55 revealed reduced migration of macrophages and decreased CD11b expression, suggesting that direct effects of CID16020046 on macrophages may have contributed to the improvement of colitis. GPR55(-/-) knockout mice showed reduced inflammation scores as compared to wild type mice in the DSS model suggesting a pro-inflammatory role in intestinal inflammation. CONCLUSIONS & INFERENCES: Pharmacological blockade of GPR55 reduces experimental intestinal inflammation by reducing leukocyte migration and activation, in particular that of macrophages. Therefore, CID16020046 represents a possible drug for the treatment of bowel inflammation.