Cannabinoid receptor type 2 is upregulated in synovium following joint injury and mediates anti-inflammatory effects in synovial fibroblasts and macrophages.

OBJECTIVE: Joint injury-induced perturbations to the endocannabinoid system (ECS), a regulator of both inflammation and nociception, remain largely uncharacterized. We employed a mouse model of ACL rupture to assess alterations to nociception, inflammation, and the ECS while using in vitro models to determine whether CB2 agonism can mitigate inflammatory signaling in macrophages and fibroblast-like synoviocytes (FLS). DESIGN: Mice underwent noninvasive ACL rupture (ACLR) via tibial compression-based loading. Nociception was measured longitudinally using mechanical allodynia and knee hyperalgesia testing. Synovitis was assessed using histological scoring and histomorphometry. Gene and protein markers of inflammation were characterized in whole joints and synovium. Immunohistochemistry assessed injury-induced alterations to CB1+, CB2+, and F4/80+ cells in synovium. To assess whether CB2 agonism can inhibit pro-inflammatory macrophage polarization, murine bone marrow-derived macrophages (mBMDM) were stimulated with IL-1ß or conditioned medium from IL-1ß-treated FLS and treated with vehicle (DMSO), the CB2 agonist HU308, or cannabidiol (CBD). Macrophage polarization was assessed as the ratio of M1-associated (IL1b, MMP1b, and IL6) to M2-associated (IL10, IL4, and CD206) gene expression. Human FLS (hFLS) isolated from synovial tissue of OA patients were treated with vehicle (DMSO) or HU308 following TNF-α or IL-1ß stimulation to assess inhibition of catabolic/inflammatory gene expression. RESULTS: ACLR induces synovitis, progressively-worsening PTOA severity, and an immediate and sustained increase in both mechanical allodynia and knee hyperalgesia, which persist beyond the resolution of molecular inflammation. Enrichment of CB2, but not CB1, was observed in ACLR synovium at 3d, 14d, and 28d, and CB2 was found to be associated with F4/80 (+) cells, which are increased in number in ACLR synovium at all time points. The CB2 agonist HU308 strongly inhibited mBMDM M1-type polarization following stimulation with either IL-1ß or conditioned medium from IL-1ß-treated mFLS, which was characterized by reductions in Il1b, Mmp1b, and Il6 and increases in Cd206 gene expression. Cannabidiol similarly inhibited IL-1ß-induced mBMDM M1 polarization via a reduction in Il1b and an increase in Cd206 and Il4 gene expression. Lastly, in OA hFLS, HU308 treatment inhibited IL-1ß-induced CCL2, MMP1, MMP3, and IL6 expression and further inhibited TNF-α-induced CCL2, MMP1, and GMCSF expression, demonstrating human OA-relevant anti-inflammatory effects by targeting CB2. CONCLUSIONS: Joint injury perturbs the intra-articular ECS, characterized by an increase in synovial F4/80(+) cells, which express CB2, but not CB1. Targeting CB2 in murine macrophages and human FLS induced potent anti-inflammatory and anti-catabolic effects, which indicates that the CB2 receptor plays a key role in regulating inflammatory signaling in the two primary effector cells in the synovium. The intraarticular ECS is therefore a potential therapeutic target for blocking pathological inflammation in future disease-modifying PTOA treatments.

[2% solution of vagothyl in the treatment of persistent otorrhea]. / 2% roztwór vagothylu w leczeniu uporczywych ropotoków usznych.

Drying of the ear in the chronic purulent otitis media prevents further lesions of the anatomic structures and allows for performing the surgery significantly decreasing the risk of any potential complications. In the search for a safe medicines that can be used for drying of the ear in persistent otorrhoea the examinations on vagothyl have been conducted. The aim of this work was to assess the outcome of treating of persistent otorrhoeas with 2% solution of vagothyl. The results were compared to those achieved when 4% vagothyl's solution was applied. The effects of the treatment with both strengths of the vagothyl's solution were similar. In case of usage of 2% solution of vagothyl there were fewer side effects. The method of treatment was modified in order to eliminate the possibility of occurring of the iatrogenic lesions.

[Enlargement of the parotid glands in bulimia nervosa and anorexia nervosa]. / Powiekszenie slinianek przyusznych w bulimia nervosa i anorexia nervosa.

Occurrence of enlargement of the parotid glands in the cases bulimia nervosa and anorexia nervosa was described. It has been stressed that possibility of the enlargement of the parotid glands in these diseases may be important for diagnosis.

[A case of Wegener's granulomatosis treatment with good outcome]. / Przypadek ziarniniaka Wegenera leczonego z dobrym wynikiem.

The case of Wegener's granulomatosis treated with good result was presented. Diagnostic difficulties of the illness and necessity of close collaboration between clinician and pathologist resulting from it were pointed.