Indirect role of α<Subscript>2</Subscript>-adrenoreceptors in anti-ulcer effect mechanism of nimesulide in rats

Nimesulide, a non-steroidal, anti-inflammatory drug, produces ulcerogenic effects in adrenalectomized rats but is gastro-protective in intact rats. The objective of this study was to determine whether adrenal gland hormones are involved in the anti-ulcer effects of nimesulide. The results revealed that 100 mg/kg nimesulide produces gastric ulceration in adrenalectomized rats, which is prevented by prednisolone and adrenaline. The anti-ulcer effects of adrenaline and prednisolone in adrenalectomized rats were in turn antagonized by yohimbine, a selective α₂-receptor blocker, but not by doxazosine (α₁-receptor blocker) or propranolol (β-blocker). Adrenaline prevented the formation of indomethacin-induced ulcers in both adrenalectomized and intact rats, but prednisolone increased the indomethacin-induced ulcerous area in intact rats, whereas it decreased the size of the ulcers in adrenalectomized rats. In addition, prednisolone prevented ulcer formation in intact rats in which the adrenaline concentration had been decreased by metyrosine. These results suggest that glucocorticoids are anti-ulcerogenic in not only adrenalectomized rats but also in intact rats with diminished circulating levels of adrenaline. In the light of these data, the effect of nimesulide on plasma adrenaline concentrations was studied. In comparison to the adrenaline levels found in intact control rats, the administration of nimesulide at doses of 10, 20, 40 and 100 mg/kg decreased adrenaline concentrations by 12.8, 22.6, 30.4, and 58.2%, respectively, without affecting blood corticosterone concentrations. The anti-ulcer effect of nimesulide was observed to be dose-dependent, and the strength of this effect was directly correlated the decreasing concentration of adrenaline. The concentration of adrenaline was decreased by 60.9% in rats treated with 300 mg/kg metyrosine in which prednisolone produced anti-ulcer effects. In summary, we have shown that nimesulide produces its anti-ulcer effect by decreasing endogenous adrenaline concentrations and that glucocorticoids may induce anti-ulcer effects via α₂-adrenoreceptors, but not via their own receptors. This research was conducted in the Laboratory of Pharmacology at Ataturk University, Faculty of Medicine, Department of Pharmacology, 25240 Erzurum/Turkey.     

Glucocorticoid signaling and exercise-induced downregulation of the mineralocorticoid receptor in the induction of adult mouse dentate neurogenesis by treadmill running

Physical exercise is known to promote adult neurogenesis, although the underlying mechanisms remain unclear. Glucocorticoid (corticosterone in rodents) is a factor that is known to affect neurogenesis. As physical exercise modulates corticosterone secretion, we hypothesized that corticosterone signaling is involved in exercise-induced adult neurogenesis. We chose treadmill running (TR) to accurately define the intensity and duration of exercise. Our results showed that 5 weeks of TR increased the doublecortin (DCX)-positive neuronal progenitor cells (NPCs) in adult hippocampus and transiently increased the serum corticosterone level at the end of the TR protocol. This protocol reduced the levels of hippocampal mineralocorticoid receptor (MR); however, glucocorticoid receptor levels were unaltered. We then investigated whether reducing corticosterone levels by bilateral adrenalectomy (ADX) attenuated the TR-enhanced adult neurogenesis. Our results showed that ADX not only blocked the TR-induced downregulation of MR, but also reduced the number of TR-enhanced NPCs. In order to examine the role of MR downregulation in TR-induced adult neurogenesis, animals were treated repeatedly with a selective MR antagonist, spironolactone, for 3 weeks. The results revealed that spironolactone increased the number of spontaneously occurring and TR-induced NPC in the dentate area. Further analysis revealed that spironolactone treatment did not alter precursor cell proliferation, but increased the number of DCX-positive NPCs, suggesting that blockage of MR signaling either facilitates the differentiation of progenitor cells towards neurons and/or enhances the survival of NPCs. Taken together, the data indicated that induction of NPCs in the dentate area of adult hippocampus by TR is partly due to the downregulation of glucocorticoid/MR signaling, which subsequently enhances differentiation along a neuronal lineage and/or NPC survival.     

肾上腺切除在库欣病治疗中的作用

目的 探讨肾上腺切除手术在库欣病治疗中的作用.方法 总结1980年1月至2005年12月收治的15例库欣病行肾上腺切除术患者临床资料,评价手术适应证、并发症和肾上腺切除手术前后患者高皮质醇血症和激素的变化.结果 15例患者均首先经蝶窦垂体手术,因术后不缓解或复发再次经蝶手术4例,垂体放疗4例.从首次经蝶手术到肾上腺切除的平均时间25.7个月(5～84个月).双侧肾上腺切除前、后的血皮质醇的中位数分别是1156.4 nmol/L和99.4 nmol/L,24 h尿游离皮质醇的中位数分别是315.0和5.4 μg,术后均需要皮质激素替代治疗.术后随访9～120个月(平均47个月),出现Nelson综合征5例(33.3%),10例未出现Nelson综合征.结论 肾上腺切除对缓解库欣病所致的高皮质醇血症是一种有效的对症治疗方法,但易出现Nelson综合征,术后需要长期激素替代治疗和定期随访.     

Intraoperative complications of laparoscopic adrenalectomy

A laparoscopic or retroperitoneoscopic access to the adrenal gland is the standard of care for adrenalectomy in most cases. Although in laparoscopic adrenalectomy the approach is minimally invasive, the procedure is challenging. This is reflected in the scope of possible complications. The surgeon must consider complications related to the anatomical topography of the adrenal gland, which typically encompasses the complications known from open surgery and complications related to the minimal invasive access. In this topic paper we will address the most frequently encountered complications of adrenalectomy: vascular injuries, injuries of the bowel, pleural tears, and injuries to the liver, spleen and pancreas. Fortunately, these complications occur rarely. However, many of these complications can have devastating consequences. Therefore, it’s the surgeon’s obligation to be aware of the possible complications he might encounter during laparoscopic adrenalectomy. This awareness is essential for their prevention and it helps the laparoscopic surgeon to identify complications intraoperatively.     

Effect of ACTH,adrenalectomy and the combination treatment on the density of 5-HT2 receptor binding sites in neocortex of rat forebrain and 5-HT2 receptor-mediated wet-dog shake behaviors

The effect of ACTH and/or adrenalectomy on serotonin (5-HT)₂ receptor binding sites was evaluated in the neocortex of rat forebrain. One day after the adrenalectomy or sham operation, ACTH (50 µg/day) was injected subcutaneously into adult male SD rats for 10 consecutive days. Saturation analysis showed that subchronic ACTH treatment significantly increased the B_max values for³H-ketanserin binding without any change in the K_d values. Moreover, this ACTH-induced increase in the B_max values was prevented by adrenalectomy. The concentrations of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) measured by HPLC-ECD were not altered by these manipulations. Ten-day administration of corticosterone (20 and 50 mg/kg) also increased 5-HT₂ receptor density in the neocortex of rat forebrain. 5-HT₂ (and 5-HT_1C) receptor agonist, (±)DOI-induced wet-dog shakes in ACTH and/or adrenalectomy-treated rats were also examined. Ten-day administration of ACTH enhanced (±)DOI-induced wet-dog shakes and this increase was prevented by adrenalectomy. These results indicate that subchronic adrenocorticotropinadrenal axis activation of rats increases both the number of 5-HT₂ receptors in neocortex of forebrain and the wet-dog shake responses induced by (±)DOI.     

Previously unreported high-grade complications of adrenalectomy

Background  Serious complications of adrenalectomy are rare but the incidence may be underestimated if they occur outside major referral centers. We report five cases of high-grade complications after adrenalectomy that have not been previously described. Methods  The records of five cases of adrenalectomy performed at outside hospitals were reviewed. Four cases were referred for management of complications and one for medical-legal review. The nature of the adrenal lesion, operative approach, complication(s), and subsequent clinical course and complication management were assessed. Both open adrenalectomy (OA) and laparoscopic adrenalectomy (LA) cases were included. Results  Operative indications were pheochromocytoma (N = 3), aldosteronoma (N = 1), and a nonfunctioning 6-cm hypervascular mass (N = 1). Complications of adrenalectomy included: case 1—complete transection of the porta hepatitis during right LA resulting in hepatic failure requiring emergent liver transplantation; case 2—ligation of the hepatic artery during right OA resulting in recurrent cholangitis and bile duct sclerosis requiring liver transplantation; case 3—ligation of the left ureter during LA resulting in postoperative hydronephrosis and loss of renal function; case 4—loss of left kidney function after OA, likely secondary to renal artery ligation ultimately requiring laparoscopic nephrectomy; case 5—LA of a normal adrenal gland for a 6-cm hypervascular mass thought to be arising from the adrenal gland. Three-month postoperative imaging demonstrated a persistent mass and the patient underwent hand-assisted laparoscopic nephrectomy for a left upper pole renal cell carcinoma that was missed at the time of LA. Conclusion  Despite the generally low morbidity of adrenalectomy, serious and potentially life-threatening complications can occur. Surgeon inexperience may be a factor in the occurrence of some of these complications which have not been previously described.     

Adrenalectomy for adrenocortical adenoma causing Cushing's syndrome in pregnancy: a case report and review of literature

We present a case of adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome diagnosed in a patient in the third trimester of her pregnancy, with an adrenal mass observed on imaging studies. Laparoscopic adrenalectomy was performed successfully at 32 weeks. To the best of our knowledge, this is the latest gestational age at which laparoscopic adrenalectomy has been reported. We present the various considerations for determining the surgical approach and the optimal timing for surgery. Adrenalectomy during pregnancy for the treatment of Cushing's syndrome caused by adrenocortical adenoma has been reported in 23 patients in the English-language medical literature to date and seems safe and beneficial. According to the data, surgical treatment has led to a reduction in perinatal mortality and maternal morbidity rates, but has not affected the occurrence of preterm birth and intrauterine growth restriction. The best outcome can be achieved by a multidisciplinary approach, with a team comprising a maternal–fetal medicine specialist, an endocrinologist and a surgeon. The timing of surgery and the surgical approach need to be determined according to the surgeon's expertise, the severity of the condition, the patient's preferences, and gestational age. Laparoscopy may prove to be the preferred surgical approach. The small number of cases precludes providing evidence-based recommendations.     

后腹腔镜手术治疗嗜铬细胞瘤

目的探讨后腹腔镜手术治疗嗜铬细胞瘤的适应证及手术安全性. 方法采用后腹腔镜手术治疗肾上腺嗜铬细胞瘤患者15例(双侧2例),腹主动脉旁嗜铬细胞瘤1例.对照组为开放手术治疗的肾上腺嗜铬细胞瘤16例,腹主动脉旁嗜铬细胞瘤1例.结果后腹腔镜手术组16例患者行后腹腔镜手术18例次,17例次取得成功,1例因术中出血改行开放手术.肿瘤最大径2.0～6.5(3.8±1.6)cm.手术时间45～150(85±31)min,出血量10～100(32±22)ml.术后吗啡用量0～40(12.5±7.8)mg;术后恢复进食时间1～3(1.8±0.7)d;下床活动时间2～3(2.3±0.5)d;术后住院时间4～9(6.5±1.3)d.开放手术组肿瘤最大径1.5～6.0(4.3±1.3)cm.手术时间90～240(155±39)min,出血量50～600(273±105)ml,9例输血.术后吗啡用量10～120(61±24)mg;术后恢复进食时间2～4(2.9±0.5)d;术后下床活动时间3～6(4.8±0.7)d;术后住院时间8～11(8.8±0.9)d.结论对于有一定腹腔镜手术经验者,后腹腔镜手术并不增加嗜铬细胞瘤手术的危险性,且具有手术时间短、出血少、创伤小、疼痛轻、康复快等优点.该法有望成为治疗肾上腺嗜铬细胞瘤的首选手术方法.