Biphasic effects of orexin-A on autonomic nerve activity and lipolysis

Previously, we showed that orexin-A, a 33-aa peptide, influences renal sympathetic nerve activity. Because the autonomic nervous system plays an important role in the regulation of lipid metabolism, we investigated the in vivo effects of orexin-A on the sympathetic nerve activity innervating white adipose tissue (WAT-SNA) and lipolysis. We found that intracerebroventricular (icv) administration of orexin-A at doses of 1mug/rat and 10ng/rat elevated and suppressed WAT-SNA, respectively. The effect of the high dose of orexin-A (1mug/rat) was eliminated by pretreatment with diphenhydramine hydrochloride, a histamine H(1) receptor antagonist. In contrast, the effect of the low dose of orexin-A (10ng/rat) was suppressed by thioperamide maleate salt, a histamine H(3) receptor antagonist. Moreover, icv administration of 1mug/rat and 10ng/rat of orexin-A increased and decreased the levels of plasma free fatty acids (FFAs), respectively. The effect of 1mug/rat of orexin-A on plasma FFA was eliminated by propranolol hydrochloride, a beta-adrenergic receptor blocker, and also by diphenhydramine. The effect of orexin-A at dose of 10ng/rat disappeared by pretreatment with atropine sulfate, a muscarinic receptor blocker, and thioperamide maleate salt. Our results suggest that high doses of orexin-A may regulate the lipolytic processes in adipose tissue through facilitation of the sympathetic nervous system, which is driven by histamine neurons through the H(1) receptor, and that the beta(3)-receptor may be involved in this enhanced lipolytic response. Low doses of orexin-A, on the other hand, may lower lipolysis by suppressing sympathetic nerve activity via the H(3)-receptor, and the muscarinic receptor may be related to this response.     

Adalimumab therapy in a patient with Crohn’s disease with a giant pelvic paraganglioma after chemotherapy

A 23-year-old man was diagnosed with a giant pelvic paraganglioma in September 2013, and a 6-month chemotherapy course was performed. The chemotherapy resulted in stable disease of the tumor for about 1 year. However, in April 2015, the patient complained of fever and diarrhea of more than ten times a day. Endoscopy showed serpiginous (snake-like) ulcers in the cecum, ascending, descending, and sigmoid colons, with granulomas without caseation histologically. The patient was diagnosed with the active stage of Crohn’s disease (CD) in June 2015. Oral mesalazine (3000 mg/day) and an elemental diet (900 kcal/day) led to temporary clinical remission. At the beginning of January in 2016, an abdominal abscess and fistula were detected by computed tomography, which needed surgical treatment. Adalimumab administration was started at the beginning of February, since active lesions were detected endoscopically. A second endoscopy showed improvement of the inflammatory lesions 3 months after induction therapy with adalimumab. Clinical remission has been maintained with adalimumab administration, with stable disease of the tumor and no adverse events. To the best of our knowledge, this is the first report of a patient with a paraganglioma who developed CD after chemotherapy. The patient was successfully treated with adalimumab after surgery for his CD.     

Involvement of oxidative stress and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in inflammatory bowel disease

The pathophysiology of inflammatory bowel disease involves excessive immune effects of inflammatory cells against gut microbes. In genetically predisposed individuals, these effects are considered to contribute to the initiation and perpetuation of mucosal injury. Oxidative stress is a fundamental tissue-destructive mechanisms that can occur due to the reactive oxygen species and reactive nitrogen metabolites which are released in abundance from numerous inflammatory cells that have extravasated from lymphatics and blood vessels to the lamina propria. This extravasation is mediated by interactions between adhesion molecules including mucosal addressin cell adhesion molecule-1 and vascular cell adhesion molecule-1 on the surface of lymphocytes or neutrophils and their ligands on endothelial cells. Thus, reactive oxygen species and adhesion molecules play an important role in the development of inflammatory bowel disease. The present review focuses on the involvement of oxidative stress and adhesion molecules, in particular mucosal addressin cell adhesion molecule-1, in inflammatory bowel disease.     

Case Report: Osteoid Osteoma of the C2 Pedicle: Surgical Technique Using a Navigation System

An osteoid osteoma of the cervical spinal pedicle is rare and carries a high surgical risk because of the close anatomic relationship to the spinal cord, nerve root, and vertebral artery. We report the case of a 12-year-old girl with an osteoid osteoma of the C2 pedicle. Computed tomograms showed an oval nidus and marked sclerosis around this lesion at the right C2 pedicle. There also was expansion of the medial and inferior cortical bone of the C2 pedicle. After failure of nonoperative treatment, we planned surgery. Owing to concerns regarding thermal damage to the spinal cord, nerve root, and/or vertebral artery using computed tomography (CT)-guided radiofrequency ablation, we curetted the nidus using a navigation system. Twenty-eight months after surgery, her pain was relieved with no limitation of cervical movement and there has been no evidence of recurrence. Navigation allowed safe curettage of the nidus through a small hole while maintaining spinal stability.     

Nuclear translocation of pro-amphiregulin induces chemoresistance in gastric cancer

Amphiregulin (AR) is derived from a membrane-anchored form (proAR) by ectodomain shedding, and is a ligand that activates epidermal growth factor receptor (EGFR). We have recently shown that proAR translocates from the plasma membrane to the nucleus after truncation of 11 amino acids at the C-terminus, which is independent of the conventional EGFR signaling pathway. Although proAR immunoreactivity has reportedly been detected in the nucleus of cancer cells, its biological meaning has never been investigated. This study was performed to investigate the roles of proAR nuclear translocation in human gastric cancer. We constructed proAR truncated 11 amino acids at the C-terminus (proARΔC11) that spontaneously translocates to the nucleus, and established proARΔC11-expression regulatable gastric cancer cells (MKN45, MKN28) using the tet-off system. Using these cells, we found that proAR nuclear translocation significantly induced chemoresistance in vitro and in vivo. Analyzing the relationship between immunoreactive localization of proAR and the clinical outcome for 46 advanced gastric cancer cases treated with chemotherapy, median survival time was 311 days in 16 patients with AR-positive staining in the nucleus and 387 days in 30 patients with AR-negative staining (P < 0.05). The present study demonstrates that proAR nuclear translocation increases resistance to anti-cancer drugs, which might be associated with poor prognosis in human gastric cancer.     

The wound/burn guidelines – 3: Guidelines for the diagnosis and treatment for diabetic ulcer/gangrene

We aimed to prepare guidelines for the management of diabetic ulcer/gangrene with emphasis on the diagnosis and treatment of skin symptoms. They serve as a tool to improve the quality of the diagnosis and treatment in each patient and, further, to improve the level of the care for diabetic ulcer in Japan by systematically presenting evidence‐based recommendations for clinical judgments by incorporating various viewpoints.     

Torsion of a Hydrosalpinx in a Virgin Patient with Mayer-Rokitansky-Küster-Hauser Syndrome: Report of a Rare Condition and Its Possible Etiology

BackgroundTo describe a rare case of hydrosalpinx torsion in a virgin patient with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.CaseA 25-year-old woman with previously diagnosed MRKH syndrome in whom lower abdominal pain led to discovery and resection of a hydosalpinx of unusual origin in a university hospital department of obstetrics and gynecology, Japan.Results and ConclusionsLaparoscopy revealed a twisted left-sided hydrosalpinx, and the mass was resected laparoscopically. Results of the blood test for Chlamydia trachomatis were positive, but results of the PCR test were negative. Our case was unusual in that hydrosalpinx is rare in virgin patients with MRKH. The cause of the hydrosalpinx was unclear, but one possibility is excess tubal secretions from the fallopian tube.     

Large or persistent lymphocyst increases the risk of lymphedema, lymphangitis, and deep vein thrombosis after retroperitoneal lymphadenectomy for gynecologic malignancy

Purpose

This retrospective study examined the incidence of lymphocyst formation after retroperitoneal lymphadenectomy in patients with gynecologic malignancy as well as the relation between lymphocyst formation and such complications as lymphedema, lymphangitis, ileus, and deep vein thrombosis (DVT).

Methods

Three hundred twenty-one patients who underwent primary surgery with pelvic (90 patients) or combined pelvic and paraaortic lymphadenectomy (231 patients) for gynecologic malignancy between January 2001 and December 2009 were enrolled. The incidences of lymphocyst identified by computed tomography at 3 weeks and 1 year after surgery were analyzed in relation to the types of surgery and types of complications.

Results

At 3 weeks after surgery, lymphocysts were observed in 282/321 patients (88 %). At 1 year after surgery, lymphocysts persisted in 69 patients (21 %). Lymphedema was observed in 34/321 (11 %) patients, lymphangitis in 36/321 (11 %), ileus in 14/321 (4 %), and DVT in 24/321 (7 %). The incidence of lymphedema was significantly greater in patients with persistent lymphocyst than in those with without (17 vs. 9 %) (p = 0.038); the incidences of lymphangitis (20 vs. 9 %) (p = 0.007) were also greater in this group. Multivariate analysis showed a large lymphocyst (>50 mm) at 3 weeks after surgery to be an independent risk factor for lymphedema (odds ratio 2.76, p = 0.009).

Conclusions

A large lymphocyst at 3 weeks after surgery or persistent lymphocyst increases the risk of lymphedema, lymphangitis, and DVT.