IntroductionCannabinoid receptor 2 (CB2R) expression is upregulated during sepsis. However, there are conflicting results regarding the effects of CB2R modulation in the hyperinflammatory phase of the disease. The aim of this study was therefore to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models.MethodsIn the endotoxemia model we studied four groups of Lewis rats: controls, lipopolysaccharide (LPS), LPS + CB2R agonist HU308 (2.5 mg/kg), and LPS + CB2R antagonist AM630 (2.5 mg/kg). In the colon ascendens stent peritonitis (CASP)-induced sepsis model we also studied four groups: sham group, CASP and CASP + CB2R agonist (HU308, 2.5 or 10 mg/kg). Intravital microscopy was performed 2 hours following LPS/placebo administration or 16 hours following CASP/sham surgery to quantify intestinal leukocyte recruitment. Additionally, hemodynamic monitoring, histological examinations and measurements of inflammatory mediators were performed.ResultsHU308 administration significantly reduced intestinal leukocyte adhesion in both acute sepsis models. The systemic levels of inflammatory mediators were significantly reduced by 10 mg/kg HU308 treatment in CASP animals.ConclusionCB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis.
A 23-year-old woman with preexisting Graves' disease who received thiamazole treatment presented with fever, dysphagia, hyperthyroidism and leukopenia. With suspicion of thyreotoxicosis accompanied by drug-induced agranulocytosis she was successfully managed by plasmapheresis, G‑CSF administration and inhibition of periphereal conversion of thyroid hormones. In due course she underwent thyroidectomy. Thiamazole is frequently associated with drug-induced agranulocytosis. Long-term therapy with thiamazole requires critical evaluation and alternatives should be considered early. Plasmapheresis is an adequate treatment option to achieve normal thyroid hormonal status.
Non-allergic rhinitis is a heterogenous group of medical diseases without an IgE-mediated pathophysiology. In this review, typical subgroups are presented with data regarding their frequency, clinical symptoms and recommendations for an effective and efficient diagnostic and therapeutic approach are indicated. The most common subtype is the non-allergic rhinopathy, also known as idiopathic or vasomotoric rhinitis. Because medication induced rhinitis is still a frequent clinical problem, a step wise approach to wean the patient is presented.
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