Induction of outward current by orexin-B in mouse peritoneal macrophages

AbstractTo define effects of novel feeding regulating peptides, orexins, in immunocompetent cells, ion channel activity in mouse peritoneal macrophages was analyzed by the perforated patch-clamp method. Orexin-B (OX-B) induced an outward current at smaller holding potentials than K+ equilibrium potentials. Reversal potentials of OX-B induced current were dependent on external K+ concentrations but not on external Cl− concentration. Orexin-A is less effective than OX-B. Quinine blocked the outward current and tetraethylammonium partially suppressed the current. These results suggest that OX-B can modulate macrophage functions through the activation of Ca2+-dependent K+ channels

PlexinD1 signaling controls domain-specific dendritic development in newborn neurons in the postnatal olfactory bulb

Newborn neurons show immature bipolar morphology and continue to migrate toward their destinations. After the termination of migration, newborn neurons undergo spatially controlled dendrite formation and change into a complex morphology. The mechanisms of dendritic development of newborn neurons have not been fully understood. Here, we show that in the postnatal olfactory bulb (OB), the Sema3E-PlexinD1 signaling, which maintains bipolar morphology of newborn neurons, also regulates their dendritic development after the termination of migration in a dendritic domain-specific manner. Genetic ablation of Sema3E or PlexinD1 enhanced dendritic branching in the proximal domain of the apical dendrites of OB newborn granule cells, whereas PlexinD1 overexpression suppressed it in a Rho binding domain (RBD)-dependent manner. Furthermore, RhoJ, a small GTPase that directly binds to PlexinD1RBD in vascular endothelial cells, is expressed in migrating and differentiating newborn granule cells in the OB and is also involved in the suppression of proximal branching of their apical dendrites. These results suggest that the Sema3E-PlexinD1-RhoJ axis regulates domain-specific dendrite formation of newborn neurons in the postnatal OB

Effects of Prolonged High Phosphorus Diet on Phosphorus and Calcium Balance in Rats

The amount of phosphorus contained in food as food additives is currently increasing and a high intake of phosphorus can cause various diseases. To determine the effects of a prolonged high phosphorus diet, here we investigated the phosphorus and calcium balance and expression of type IIa sodium-dependent phosphate transporter (Npt IIa) in mature rats. Wistar male rats (8-weeks old) were divided into five groups and fed diets containing 0.6% calcium plus 0.3, 0.6, 0.9, 1.2 or 1.5% phosphorus for 4 weeks. Urinary and fecal phosphorus excretions were significantly increased by the high phosphorus diets (from 0.6 to 1.5%), dependent on the amount of dietary phosphorus. The net absorption of intestinal phosphorus was also significantly increased by high phosphorus diets. As a result, a negative phosphorus balance was observed in rats given the 1.2% or 1.5% phosphorus diets. Serum parathyroid hormone and 1,25-dihydroxyvitamin D3 concentrations were increased by high phosphorus diets. In addition, high phosphorus diets decreased the expression of Npt IIa mRNA and protein in the renal brush border membrane. Taken together, these results suggest that diets containing 1.2 or 1.5% phosphorus plus 0.6% calcium have potentially adverse effects on phosphorus homeostasis in mature rat

Soluble Siglec-9 suppresses arthritis in a collagen-induced arthritis mouse model and inhibits M1 activation of RAW264.7 macrophages

Background: The aim of this study was to assess the effects of soluble sialic acid-binding immunoglobulin-type lectin (sSiglec)-9 on joint inflammation and destruction in a murine collagen-induced arthritis (CIA) model and in monolayer cultures of murine macrophages (RAW264.7 cells and peritoneal macrophages) and fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis. Methods: DBA/1J mice were immunized with type II collagen. Effects of sSiglec-9 were evaluated using a physiologic arthritis score, histological analysis, serum tumor necrosis factor (TNF)-α concentration, and the proportion of forkhead box P3 (Foxp3)-positive regulatory T (Treg) cells. In vivo biofluorescence imaging was used to assess the distribution of sSiglec-9. Levels of M1 (TNF-α, interleukin [IL]-6, and inducible nitric oxide synthase) and M2 (CD206, Arginase-1, and IL-10) macrophage markers and phosphorylation of intracellular signaling molecules were examined in macrophages, and levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were examined in FLS. Results: sSiglec-9 significantly suppressed the clinical and histological incidence and severity of arthritis. The proportion of Foxp3-positive Treg cells significantly improved and serum TNF-α concentration decreased in vivo. Although sSiglec-9 reduced the expression of M1 markers in macrophages, it did not affect the expression of M2 markers and MMPs in FLS. Nuclear factor (NF)-kB p65 phosphorylation was attenuated by sSiglec-9, and chemical blockade of the NF-kB pathway reduced M1 marker expression in RAW264.7 cells. Conclusions: In this study, we have demonstrated the therapeutic effects of sSiglec-9 in a murine CIA model. The mechanism underlying these effects involves the suppression of M1 proinflammatory macrophages by inhibiting the NF-kB pathway. sSiglec-9 may provide a novel therapeutic option for patients with rheumatoid arthritis refractory to currently available drugs

Predictors of Hypotension after Adrenalectomy for Pheochromocytoma

The management of blood pressure is a significant concern for surgeons and anesthesiologists performing adrenalectomy for pheochromocytoma. We evaluated clinical factors in pheochromocytoma patients to identify the predictors of postoperative hypotension. The medical records of patients who underwent adrenalectomy for pheochromocytoma between 2001 and 2017 were retrospectively reviewed and clinical and biochemical data were evaluated. Of 29 patients, 13 patients needed catecholamine support in the perisurgical period while 16 patients did not. There were significant differences in median age, tumor size, and blood pressure drop (maxmin) between the 2 groups (68 vs 53 years old, p=0.045; 50 vs 32 mm diameter, p=0.022; 110 vs 71 mmHg, p=0.015 respectively). In univariate logistic analysis, age > 65.5 years, tumor size > 34.5 mm, urine metanephrine > 0.205 mg/day and urine normetanephrine > 0.665 mg/day were significant predictors of prolonged hypotension requiring postoperative catecholamine support. Tumor size and urine metanephrine and urine normetanephrine levels were correlated with postoperative hypotension. These predictors may help in the safe perioperative management of pheochromocytoma patients treated with adrenalectomy

[1.1]meta-Stilbenophanes as calixarene analogs: preparation, crystal structure, and cis-trans photoisomerization

Abstract-Three isomers of [1.1]meta-stilbenophane were synthesized by the McMurry reaction of diarylmethane dialdehyde and their crystal structures and photochemical properties were investigated. X-ray crystallographic analyses of these isomers revealed that they were assigned to a trans-trans (t-t) form with a 1,3-alternate conformation, a cis-trans (c-t) form with a distorted-cone conformation, and a cis-cis (c-c) form with a 1,2-alternate conformation. A 1 H NMR study indicated that a t-t isomer could be completely transformed into a 35:65 mixture of c-t and c-c isomers by photoirradiation at 254 nm