Background and purpose:This study investigates the role of a2-adrenoceptor subtypes, a2A, a2B and a2C, on catecholamine synthesis and catabolism in the central nervous system of mice. Experimental approach: Activities of the main catecholamine synthetic and catabolic enzymes were determined in whole brains obtained from a2A-, a2B-and a2C-adrenoceptor knockout (KO) and C56Bl\7 wild-type (WT) mice. Key results: Although no significant differences were found in tyrosine hydroxylase activity and expression, brain tissue levels of 3,4-dihydroxyphenylalanine were threefold higher in a2A-and a2C-adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in a2A and a2CKOs compared with WT [WT: 2.8 Ϯ 0.5, 1.1 Ϯ 0.1; a2AKO: 6.9 Ϯ 0.7, 1.9 Ϯ 0.1; a2BKO: 2.3 Ϯ 0.2, 1.0 Ϯ 0.1; a2CKO: 4.6 Ϯ 0.8, 1.5 Ϯ 0.2 nmol·(g tissue), for dopamine and noradrenaline respectively]. Aromatic L-amino acid decarboxylase activity was significantly higher in a2A and a2CKO [WT: 40 Ϯ 1; a2A: 77 Ϯ 2; a2B: 40 Ϯ 1; a2C: 50 Ϯ 1, maximum velocity (Vmax) in nmol·(mg protein)], but no significant differences were found in dopamine b-hydroxylase. Of the catabolic enzymes, catechol-O-methyltransferase enzyme activity was significantly higher in all three a2KO mice [WT: 2.0 Ϯ 0.0; a2A: 2.4 Ϯ 0.1; a2B: 2.2 Ϯ 0.0; a2C: 2.2 Ϯ 0.0 nmol·(mg protein)], but no significant differences were found in monoamine oxidase activity between all a2KOs and WT mice. Conclusions and implications:In mouse brain, deletion of a2A-or a2C-adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any a2-adrenoceptor subtypes resulted in increased activity of catechol-O-methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in a2A and a2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport.

Background Targeted axillary dissection (TAD) combines sentinel node biopsy (SNB) with the removal of the previously marked metastatic node. TAD is a promising concept for axillary restaging in node-positive breast cancer patients with pathological complete response (pCR) to neoadjuvant therapy (NAT). We aimed to evaluate TAD feasibility in this context. Methods A prospective observational study was conducted in biopsy-confirmed cN1 patients. The removal of the clipped node (CN) was guided by intraoperative ultrasound. SNB used indocyanine green and patent blue V dye. If the CN or sentinel lymph nodes (SLN) had any metastatic foci, or the TAD procedure was unsuccessful, the patient underwent axillary lymph node dissection (ALND). Results Thirty-seven patients were included. TAD and SNB identification rates were 97.3%. Every retrieved CN was also a SLN. At the individual level, SNB identification rate was 89.2% with indocyanine green and 85.5% with patent blue V dye. The CN identification rate was 81.1%, being higher when the CN was localized on the intraoperative ultrasound (84.4% vs 60.0%). Nodal pCR was achieved by 54.1% of our patients and was more frequent in HER2-positive and triple-negative tumors ( p = 0.039). Nineteen patients were spared from ALND. Conclusion TAD with intraoperative ultrasound-guided excision of the CN and SNB with indocyanine green and patent blue V dye is a feasible concept to identify patients without axillary residual disease after NAT, that can be spared from ALND, although the need for marking the biopsied node should be further investigated.