Soluble epoxide hydrolase inhibitor blockage microglial cell activation in subnucleus caudalis in a persistent model of arthritis.

Rheumatoid arthritis (RA) is a chronic condition characterized by pain and infiltration of immune cells into the joint. Immune cells can be activated, producing inflammatory cytokines, leading to continuously degenerative and inflammatory reactions and the temporomandibular joint (TMJ) can be affected by RA. In this scenario, novel targets are needed to increase treatment efficacy with minimized side effects. The epoxy-eicosatrienoic acids (EETs), are endogenous signaling molecules, playing important roles in diminishing inflammation and pain but are promptly metabolized by soluble epoxide hydrolase (sEH), generating less-bioactive acids.Therefore, sEH inhibitors is an interest therapeutic target to enhance the beneficial effect of natural EETs. TPPU is a potent sEH inhibitor that is capable of dampening EETs hydrolysis. Thus, we aimed to assess the impact of pharmacological sEH inhibition on a persistent model of albumin-induced arthritis in the TMJ, in two scenarios: first, as post-treatment, in an installed arthritic condition, and second, the protective role, in preventing the development of an arthritic condition. In addition, we investigate the influence of sEH inhibition on microglia cell activation in the trigeminal subnucleus caudalis (TSC) and in vitro experiments. Finally, we examined the astrocyte phenotype. Oral administration of TPPU, acts in multiple pathways, in a protective and reparative post-treatment, ameliorating the preservation of the TMJ morphology, reducing the hypernociception, with an immunosuppressive action reducing neutrophil and lymphocytes and pro-inflammatory cytokines in the TMJ of rats. In TSC, TPPU reduces the cytokine storm and attenuates the microglia activated P2X7/Cathepsin S/Fractalkine pathway and reduces the astrocyte activation and glutamate levels. Collectively, our findings revealed that sEH inhibition mitigates hypersensitive nociception through the regulation of microglia activation and astrocyte modulation, demonstrating the potential use of sEH inhibitors as immunoresolvents in the treatment of autoimmune disorders.

A Novel Technique for Transpalatal Hypophysectomy.

Objective A novel technique is described for transpalatal hypophysectomy as an option for sellar region surgery using a microscope and/or endoscope. Technique A straight submucosal tunnel (approximately 20 mm in diameter; 40-50 mm long-half the length required by conventional transsphenoidal hypophysectomy) is dissected in favorable alignment with the main tumor axis, providing a direct view that allows the surgeon to operate on large suprasellar tumors, even in cases of extra-axial expansion. Results In a 25-year period, over 50 patients benefited from this surgery. Macroadenomas devoid of extra-axial expansions were totally excised (76.5%), otherwise, partially (23.5%). Forty-nine patients (98%) were extubated soon after surgery. Mean surgery duration was 3 hour 32 minute, with 2 days 6 hour before free feeding was restored. Postoperative hospitalization under neurosurgical care averaged 6 days 6 hour. Currently, patients undergoing the procedure do not require nasal tampons and can eat soft foods soon after recovery from anesthesia. Although two patients (3.9%) presented with oronasal fistulae postoperatively, no episodes of severe hemorrhage occurred during surgery and there were no cases of liquoric fistulae, visual impairment, panhypopituitarism, or severe syndrome of inappropriate antidiuretic hormone secretion. Conclusion The new surgical approach is safe, effective, and well accepted by patients, who reported low levels of discomfort. Postsurgical complications or sequela are currently rare, but further operations should be performed using more appropriate materials, instruments, and equipment to allow comparisons with other techniques.