BACKGROUNDLittle is known of the effects of hydrocortisone on cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and its counterreceptors (LFA-1, Mac-1) in acute pancreatitis (AP). We investigated the effects of prior treatment with hydrocortisone on the production of ICAM-1 and its counterreceptors (LFA-1 and Mac-1) in AP of rats to clarify the effect of hydrocortisone on induced acute pancreatitis.

METHODSAcute pancreatitis was induced by infusion of 5% chenodeoxycholic acid into the pancreatic duct, followed by ligation of pancreatic duct. Before induction of acute pancreatitis, rats were treated with hydrocortisone (n = 20) or 0.9% saline (n = 20). Blood and specimens from pancreas and lung were obtained from 5 rats from each treatment euthanized at 1 hour or 3 hours, 6 hours, 12 hours. Expression of ICAM-1 was assessed by immunohistochemistry and Western blot analysis of pancreas and lungs. The expression of LFA-1 and Mac-1 on neutrophils was detected by flow cytometer. The therapeutic effect of hydrocortisone was assessed from injuries to pancreas and lung.

RESULTSICAM-1 expression in the pancreas of hydrocortisone group was significantly less than in control group at 3 hours and 6 hours. In the lungs of hydrocortisone group, ICAM-1 expression was significantly less than in control group at 3 hours, 6 hours and 12 hours. The expression of LFA-1 and Mac-1 on neutrophils in blood increased significantly in control group over hydrocortisone group. Increased expression of ICAM-1, LFA-1 and Mac-1 preceded leukocyte infiltration. Compared to untreated animals with acute pancreatitis, rats pretreated with hydrocortisone had significantly reduced histological lung injury and output of ascitic fluid.

CONCLUSIONSPrior treatment with hydrocortisone before the induction of acute pancreatitis ameliorates pulmonary injury and the output of ascitic fluid and reduces the expression of ICAM-1 and its counterreceptors (LFA-1, Mac-1) in acute pancreatitis.

Acute Disease ; Amylases ; blood ; Animals ; Hydrocortisone ; pharmacology ; therapeutic use ; Intercellular Adhesion Molecule-1 ; analysis ; Lymphocyte Function-Associated Antigen-1 ; blood ; Macrophage-1 Antigen ; blood ; Pancreatitis ; blood ; drug therapy ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: Palonosetron is effective for the management of acute and delayed chemotherapy-induced nausea and vomiting (CINV). While emetogenic carboplatin-based chemotherapy is widely used to treat gynecologic cancers, few studies have evaluated the antiemetic effectiveness of palonosetron in this setting. METHODS: A multicenter, single-arm, open-label phase II trial was conducted to evaluate the safety and effectiveness of palonosetron in controlling CINV in patients with gynecologic cancer. Chemotherapy-naïve patients received intravenous palonosetron (0.75 mg/body) and dexamethasone before the infusion of carboplatin-based chemotherapy on day 1. Dexamethasone was administered (orally or intravenously) on days 2–3. The incidence and severity of CINV were evaluated using the patient-completed Multinational Association of Supportive Care in Cancer Antiemesis Tool and treatment diaries. The primary endpoint was the proportion of patients experiencing complete control (CC) of vomiting, with “no rescue antiemetic medication” and “no clinically significant nausea” or “only mild nausea” in the delayed phase (24–120 hours post-chemotherapy). Secondary endpoints were the proportion of patients with a complete response (CR: “no vomiting” and “no rescue antiemetic medication”) in the acute (0–24 hours), delayed (24–120 hours), and overall (0–120 hours) phases, and CC in the acute and overall phases. RESULTS: Efficacy was assessable in 77 of 80 patients recruited. In the acute and delayed phases, the CR rates the primary endpoint, were 71.4% and 59.7% and the CC rates, the secondary endpoint, were 97.4% and 96.1%, respectively. CONCLUSION: While palonosetron effectively controls acute CINV, additional antiemetic management is warranted in the delayed phase after carboplatin-based chemotherapy in gynecologic cancer patients (Trial registry at UMIN Clinical Trials Registry, UMIN000012806).
Antiemetics ; Carboplatin ; Dexamethasone* ; Drug Therapy* ; Female ; Genital Neoplasms, Female ; Humans ; Incidence ; Japan* ; Nausea* ; Vomiting*