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Prolactin (Prl) and growth hormone (Gh) as well as insulin-like growth factor 1 (Igf1) are involved in the physiological adaptation of fish to varying salinities. The Igfs have been also ascribed other physiological roles during development, growth, reproduction and immune regulation. However, the main emphasis in the investigation of osmoregulatory responses has been the endocrine, liver-derived Igf1 route and local regulation within the liver and osmoregulatory organs. Few studies have focused on the impact of salinity alterations on the Gh/Igf-system within the neuroendocrine and immune systems and particularly in a salinity-tolerant species, such as the blackchin tilapia Sarotherodon melanotheron. This species is tolerant to hypersalinity and saline variations, but it is confronted by severe climate changes in the Saloum inverse estuary. Here we investigated bidirectional effects of increased salinity followed by its decrease on the gene regulation of prl, gh, igf1, igf2, Gh receptor and the tumor-necrosis factor a. A mixed population of sexually mature 14-month old blackchin tilapia adapted to freshwater were first exposed to seawater for one week and then to fresh water for another week. Brain, pituitary, head kidney and spleen were excised at 4 h, 1, 2, 3 and 7 days after both exposures and revealed differential expression patterns. This investigation should give us a better understanding of the role of the Gh/Igf system within the neuroendocrine and immune organs and the impact of bidirectional saline challenges on fish osmoregulation in non-osmoregulatory organs, notably the complex orchestration of growth factors and cytokines.

The tight junction protein claudin-3 is overexpressed in diverse epithelial tumours and is associated with increased survival, progression and motility of tumour cells. Claudin-3 expression profiles are being increasingly used for diagnostic and prognostic tumour classification. Claudin-3 has been identified as a receptor for Clostridium perfringens enterotoxin, which is under consideration for selective lysis of claudin-3- expressing tumours, particularly brain metastases, and other translational medicine uses. However, the localization of claudin-3 in the brain has not been completely elucidated. While claudin-3 in brain tissue adjacent to claudin-3-expressing metastases had been excluded and low or undetectable levels proposed in the CNS, under physiological conditions, in adult human, rat and mouse brains, claudin-3 was exclusively found in choroid plexus epithelium where it is considered an integral component of the blood-cerebrospinal-fluid barrier. We report here the pronounced presence of claudin-3 not only in the nasal region (as described for rat), but also in the mouse olfactory bulb and nerve using immunohistochemistry and Western blot. Claudin-3 was present in the fila olfactoria from the epithelium to the olfactory nerve and in the main and accessory olfactory bulb. We propose that the abundant presence of claudin3 in the olfactory system, particularly in nerve fibres and the olfactory bulb cone, which we present here, may play a role at the interface of the central and peripheral nervous system, both as barrier and for axonal growth and communication. Thus, claudin-3 should be considered and further explored with regards to treatment approaches addressing the olfactory bulb and nasal region.

Background For optimal prosthetic anchoring in omarthritis surgery, a differentiated knowledge on the mineralisation distribution of the glenoid is important. However, database on the mineralisation of diseased joints and potential relations with glenoid angles is limited. Methods Shoulder specimens from ten female and nine male body donors with an average age of 81.5 years were investigated. Using 3D-CT-multiplanar reconstruction, glenoid inclination and retroversion angles were measured, and osteoarthritis signs graded. Computed Tomography-Osteoabsorptiometry (CT-OAM) is an established method to determine the subchondral bone plate mineralisation, which has been demonstrated to serve as marker for the long-term loading history of joints. Based on mineralisation distribution mappings of healthy shoulder specimens, physiological and different CT-OAM patterns were compared with glenoid angles. Results Osteoarthritis grades were 0-I in 52.6% of the 3D-CT-scans, grades II-III in 34.3%, and grade IV in 13.2%, with in females twice as frequently (45%) higher grades (III, IV) than in males (22%, III). The average inclination angle was 8.4°. In glenoids with inclination ≤10°, mineralisation was predominantly centrally distributed and tended to shift more cranially when the inclination raised to > 10°. The average retroversion angle was − 5.2°. A dorsally enhanced mineralisation distribution was found in glenoids with versions from − 15.9° to + 1.7°. A predominantly centrally distributed mineralisation was accompanied by a narrower range of retroversion angles between − 10° to − 0.4°. Conclusions This study is one of the first to combine CT-based analyses of glenoid angles and mineralisation distribution in an elderly population. The data set is limited to 19 individuals, however, indicates that superior inclination between 0° and 10°-15°, and dorsal version ranging between − 9° to − 3° may be predominantly associated with anterior and central mineralisation patterns previously classified as physiological for the shoulder joint. The current basic research findings may serve as basic data set for future studies addressing the glenoid geometry for treatment planning in omarthritis.

Tumor necrosis factor-alpha (TNF-α) plays an important role in liver inflammation. CD40- CD40 ligand (CD40-CD40L) is a key receptor-ligand signaling pair involved in the adaptive immune response and pathogenesis of autoimmune diseases. In mice, CD40 activation leads to sickness behavior syndrome (SBS) comprising weight loss, sleep disruption and depression, which can be blocked by administration of the TNF-inhibitor etanercept. In the present study, we assessed the extent of hepatic inflammation in mice devoid of the TNF-receptor 1 (TNFR1)-mediated signaling pathway. The TNFR1-depleted (TNFR1-/-) adult mice and their wild type littermates were given a single intra-peritoneal injection of CD40 agonist monoclonal antibody (mAb) or rat IgG2a isotope control. As described previously, TNFR1-/- mice were protected from SBS upon CD40 mAb treatment. Cd40, tnf and tnfr1 mRNA and Tnf-α peptide were increased in the liver of CD40 mAbstimulated wild type mice. Serum alanine aminotransferase was elevated in both CD40-activated wild type and TNFR1-/- mice. TNFR1-/- mice showed much less intra-parenchymal infiltrates, hepatocellular necrosis, and perivascular clusters upon CD40 mAb activation than their wild type littermates. A gene expression microarray detected increased activity of metabolic and detoxification pathways and decreased activity of inflammatory pathways. We conclude that immune activation and development of liver inflammation in CD40L interactions depend on TNFR1-mediated signaling pathways and are counteracted by alterations in metabolic pathways., Biomedicines, 9 (8)

Tissue-nonspecific alkaline phosphatase (TNAP) is playing a key role in bone calcification, as has been demonstrated in different mammalian species including human and rodents. However, to investigate age-related changes during life history, histochemical demonstration of TNAP is severely hampered, particularly in the elderly, by technical difficulties associated with sectioning calcified tissue. Sufficient fixation must precede decalcification since poorly fixed bone tissue is exposed to the deleterious effects of decalcification reagents. In order to find a method that would allow cryosectioning of bone without loss of TNAP activity, we assessed the efficacy of different fixation reagents regarding the effects on structural integrity and TNAP activity using liver and osseous tissue from younger and older horses. The results of this study reveal that glyoxal-based fixatives sufficiently preserved bone tissue for successful cryosectioning without compromising TNAP activity. The method described combines the demonstration of TNAP activity with optimal preservation of tissue morphology in osseous tissue of younger and even of older mammals. As a model species, we selected horse bones in light of potentially higher similarities to ageing history and lifelong locomotion in humans as compared to other, mostly smaller, experimental model species with a much shorter life span and artificial locomotive activity when kept in cages. This may serve as a basis for future studies addressing the impact of different life traits in iconic, domestic and companion animals, which are often patients in veterinary medicine, as well as for basic research on human physiology and pathologies of the musculoskeletal system.

International audience; A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine) IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

Like in humans, diabetes mellitus is on the rise in cats. Feline diabetes is a suitable model for human type-2 diabetes. We investigated magnitude and timing of insulin suppression with induced hyperglycaemia and its relationship to plasma and urinary ketones and to pancreatic islet insulin. IGF-I is under discussion as a protective mechanism but little is known about its role in diabetes in general and its distinct localisation in feline pancreatic islets in particular. Thirteen healthy, adult cats were allocated to 2 groups and infused with glucose to maintain their blood glucose at a high or moderate concentration for 42 days resulting in insulin secretion suppression. After initial increase, insulin levels declined to baseline but were still detectable in the blood at a very low level after 6 weeks of glucose infusion and then increased after a 3 week recovery period. While IGF-I in healthy cats was primarily located in glucagon cells, in hyperglycaemia-challenge IGF-I was pronounced in the β-cells 3 weeks after ceasation of infusion. Six/8 cats developing glucose toxicity became ketonuric after 3–4 weeks. Gross lipaemia occurred approx 1 week prior to ketonuria. Ketonuric cats required 1–2 weeks of insulin therapy after-infusion until β-cell recovery. In conclusion, ketosis and hyperlipidaemia are likely to occur in diabetic cats with glucose at 30 mmol/L, especially after ⩾2 weeks. Three weeks after ceasation of infusions, clinical and morphological recovery occurred. We propose a local protective effect of IGF-I to support survival and insulin production in the hyperglycaemic state and recovery period.