Regulatory T cells confer a circadian signature on inflammatory arthritis.

The circadian clock is an intrinsic oscillator that imparts 24 h rhythms on immunity. This clock drives rhythmic repression of inflammatory arthritis during the night in mice, but mechanisms underlying this effect are not clear. Here we show that the amplitude of intrinsic oscillators within macrophages and neutrophils is limited by the chronic inflammatory environment, suggesting that rhythms in inflammatory mediators might not be a direct consequence of intrinsic clocks. Anti-inflammatory regulatory T (Treg) cells within the joints show diurnal variation, with numbers peaking during the nadir of inflammation. Furthermore, the anti-inflammatory action of Treg cells on innate immune cells contributes to the night-time repression of inflammation. Treg cells do not seem to have intrinsic circadian oscillators, suggesting that rhythmic function might be a consequence of external signals. These data support a model in which non-rhythmic Treg cells are driven to rhythmic activity by systemic signals to confer a circadian signature to chronic arthritis.

Unique Tailoring of Th17 at the Gingival Oral Mucosal Barrier.

Our recent work highlights unique requirements for the induction of Th17 cells at the oral/gingival mucosal barrier. Unlike other barrier sites, such as the skin and gastrointestinal tract, we found that Th17 cells can develop at the gingiva independently of commensal microbiota colonization. Instead, we identified that damage, which occurs physiologically due to mastication, promotes induction of Th17 cells and tones homeostatic immunity at the gingiva.

Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis.

The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of nuclear factor (NF)κB through Gαi. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NFκB inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis.

[Opioid peptides in hemorrhagic shock]. / Opioidpeptide im hämorrhagischen Schock.

Regarding the treatment of vitally endangered intensive care patients the neuroendocrine regulation of the post-aggression metabolism is important. The role of opioid peptides in this system is investigated in the animal experiment "Haemorrhagic Shock in the Dog". It was shown that the opioid peptide beta-endorphin and metenkephalin rise grossly in connection with pathological and endocrinological alterations in shock. Based on the literature the role of increased concentration of opioids in haemorrhagic shock is discussed and conclusions for therapeutic measures are presented.

[An animal model of surgical, external cardiac denervation. Studies of the autonomic control of heart rate]. / Tiermodell der operativen, externen kardialen Denervierung Untersuchungen zur neurovegetativen Herzfrequenzsteuerung.

A great role is played in clinical practice by monitoring of vegetative functions, such as heart and respiratory rates. Mean values, rhythms, and interaction of both control variables in the form of respiratory sinus arrhythmia may provide plenty of information, primarily when computerised, and may enable conclusions to be drawn as to neuro-circulatory tonus. The model described in this paper has been devised for the purpose of producing information on types of changes in neurovegetative control in response to functional systemic effects from pharmaceuticals or from substantial, locally delimited lesions of nerve structures. External cardiac denervation is applied for stepwise discontinuation of sympathetic, parasympathetic, spinal, and medullary control systems up to the stage of cerebral death, resulting in cardiac "automatism". Data may thus be derived on the Bainbridge reflex, and correlations may be established with in vitro experiments on chronotropic control of the heart. The results presented in this paper may be of relevance to situations in intensive medical care or to cases with lesions to the central nervous system up to irreversible loss of brain function, when heart rate data recorded from monitoring of the central nervous system or of vegetative functions must be interpreted in all their variability with high reliability and accuracy for differential diagnosis and prognostication.

[Oxygen requirements of the isolated dog pancreas]. / Zum Sauerstoffbedarf des isolierten Hundepankreas.

This contribution reports about the oxygen requirement of the isolated perfused dog pancreas. A solution with the content of red blood corpuscles, a stroma-free hemoglobin solution or a perfusate--free from oxygen carriers--were applied. The oxygen requirement of the pancreas amounts to 0.59 ml/min . 100 g. The oxygen supply of the organ is possible with a flow of 0.50 ml/min . g and an oxygen partial pressure of 65 kPa (487.5 mmHg) also by means of a perfusate free from oxygen carriers.

[Effect of potassium concentration of the perfusion solution on organ resistance of the perfused dog pancreas]. / Der Einfluss der Kaliumkonzentration in der Perfusionslösung auf den Organwiderstand des perfundierten Hundepankreas.

The influence of different potassium concentrations in the perfusate on the perfusion pressure of isolated dog pancreas is reported. A potassium concentration above 30 mmol/l leads both under hypothermic and normothermic conditions to an increase of the vascular resistance, That's why organs with a small blood flow should be perfused with solutions poor in potassium also in the initial perfusion.