Identification of novel H3 receptor (H3R) antagonists with cognition enhancing properties in rats

Inflammation Research -     

Early life social stress induced changes in depression and anxiety associated neural pathways which are correlated with impaired maternal care

Exposures to various types of early life stress can be robust predictors of the development of psychiatric disorders, including depression and anxiety. The objective of the current study was to investigate the roles of the translationally relevant targets of central vasopressin, oxytocin, ghrelin, orexin, glucocorticoid, and the brain-derived neurotrophic factor (BDNF) pathway in an early chronic social stress (ECSS) based rodent model of postpartum depression and anxiety. The present study reports novel changes in gene expression and extracellular signal related kinase (ERK) protein levels in the brains of ECSS exposed rat dams that display previously reported depressed maternal care and increased maternal anxiety. Decreases in oxytocin, orexin, and ERK proteins, increases in ghrelin receptor, glucocorticoid and mineralocorticoid receptor mRNA levels, and bidirectional changes in vasopressin underscore related work on the adverse long-term effects of early life stress on neural activity and plasticity, maternal behavior, responses to stress, and depression and anxiety-related behavior. The differences in gene and protein expression and robust correlations between expression and maternal care and anxiety support increased focus on these targets in animal and clinical studies of the adverse effects of early life stress, especially those focusing on depression and anxiety in mothers and the transgenerational effects of these disorders on offspring.     

Gastric variceal bleeding caused by an intrahepatic arterioportal fistula that formed after liver biopsy: a case report and review of the literature

An intrahepatic arterioportal fistula is a rare cause of portal hypertension and variceal bleeding. We report on a patient with an intrahepatic arterioportal fistula following liver biopsy who was successfully treated by hepatectomy after unsuccessful arterial embolization. We also review the literature on symptomatic intrahepatic arterioportal fistulas after liver biopsy. A 48-year-old male with bleeding gastric varices and hepatitis B virus-associated liver cirrhosis was transferred to our hospital; this patient previously underwent percutaneous liver biopsies 3 and 6 years ago. Abdominal examination revealed a bruit over the liver, tenderness in the right upper quadrant, and splenomegaly. Ultrasonographic examination, computed tomography, and angiography confirmed an arterioportal fistula between the right hepatic artery and the right portal vein with portal hypertension. After admission, the patient suffered a large hematemesis and developed shock. He was treated with emergency transarterial embolization using microcoils. Since some collateral vessels bypassed the obstructive coils and still fed the fistulous area, embolization was performed again. Despite the second embolization, the collateral vessels could not be completely controlled. Radical treatment involving resection of his right hepatic lobe was performed. For nearly 6 years postoperatively, this patient has had no further episodes of variceal bleeding.     

Autogenous vein graft from iliac artery to splenic artery for celiac occlusion in pancreaticoduodenectomy

This is a report of two patients with bile duct cancer and periampullary cancer with celiac axis occlusion who underwent pylorus-preserving pancreaticoduodenectomy and pancreaticoduodenectomy, respectively. Preoperative arteriography demonstrated complete obstruction of the celiac axis. The arterial blood flow to the liver, spleen, and stomach was sustained through the pancreaticoduodenal arcades and collaterals from the superior mesenteric artery. Therefore, reconstruction of the celiac axis circulation was required before division of the gastroduodenal artery. An autograft of the saphenous vein was placed between the iliac artery and the splenic artery, and subsequently pancreaticoduodenectomy was performed. The patients' postoperative courses were uneventful. Postoperative arteriography demonstrated patency of the grafts. When occlusion of the celiac axis exists, a bypass from the iliac artery to the splenic artery using a saphenous vein graft, may be safely and easily performed at the time of pancreaticoduodenal resection.     

Long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer

Background and aims The purpose of this study was to assess the long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer. Materials and methods Between April 1990 and June 2005, all patients who underwent surgery for low rectal cancer with a pretreatment diagnosis of T3 or resectable T4 without distant metastasis were enrolled. The total dose of radiation was 45 Gy. Patients with a partial or complete response were defined as radiotherapy responders (RT-R) and the others as radiotherapy non-responders (RT-NR). Patients who did not receive radiotherapy were termed the non-radiotherapy group (NRT). The endpoint of this study was overall survival and local and/or distant metastasis. Results There were 24 patients in RT-R, 26 in RT-NR, and 40 in NRT. Gastrointestinal complications were commonly observed in all groups. RT-R had a significantly higher incidence of genitourinary complications. Five-year overall survival rate was 79.6% in RT-R, 58.9% in RT-NR, and 58.8% in NRT. The difference was significant in favor of RT-R over the others (P = 0.015, 0.024, respectively). Five-year local recurrence-free survival rate was 100% in RT-R, 81.5% in RT-NR, and 74.9% in NRT. RT-R had significantly improved local control compared with the others (P = 0.034, 0.021, respectively). Five-year distant metastasis-free survival was not statistically different among all groups. Conclusions Survival benefit of preoperative radiotherapy was limited to responders. Considering the increased risk of adverse effects, identification of predictors of radiosensitivity is required in order to provide the most suitable treatment for individual patients.     

Ultrasonographic evaluation in patients with autoimmune-related pancreatitis

Background The concept of autoimmune-related pancreatitis (AIP) has recently been described. It is important to exclude pancreaticobiliary malignancy in patients with AIP who develop distal bile duct strictures. The aim of this study was to evaluate distal common bile duct strictures in AIP patients by endoscopic ultrasonography (EUS), intraductal ultrasonography (IDUS), and contrast-enhanced EUS (ceEUS).Methods Five patients with AIP, encountered from January 2000 through December 2001, underwent EUS, IDUS, and ceEUS, using Levovist as a contrast medium. EUS and ceEUS were used to follow changes in distal bile duct strictures in three of these five patients following a trial of steroid therapy.Results Of the five patients, four had cholestatic biochemical profiles, three were positive for autoantibodies, and three had elevated serum immunoglobulin G (IgG) or IgG4. A diffusely enlarged pancreas, narrowing of the main pancreatic duct (MPD), and strictured common bile duct in the pancreatic head were features common to all patients. Pretherapy EUS or IDUS imaging showed concentric wall thickening of the distal common bile duct causing bile duct stenosis. ceEUS showed diffuse strong enhancement of the thickened bile duct wall, possibly due to inflammation. After the steroid therapy, the stenotic lesions in both the MPD and distal common bile duct were rapidly attenuated, with a decline in biochemical cholestatic enzymes and serum IgG or IgG4 levels.Conclusions On EUS and IDUS imaging, concentric bile duct wall thickening and its strong enhancement by Levovist was characteristic in AIP patients.     

Spectrum of traumatic brain injury from mild to severe

Traumatic brain injury (TBI) involves significant damage of the brain parenchyma, and is the leading cause of morbidity and mortality after trauma. It is thus essential for all physicians involved in acute care medicine and surgery to have a thorough understanding of TBI. Management of the patient with TBI is a rapidly advancing field, characterized by an improved understanding of intracranial pathophysiology and decreasing overall mortality largely because of improved neurocritical and surgical care. This article summarizes the classification system, management approaches, and recent controversies in the care of mild, moderate, and severe TBI.     

Colorectal cancer: the potential of metabolic fingerprinting

Metabolomics is a relatively new omics science that can provide a strong individual small-molecule fingerprint. Disease onset can be monitored as a deviation from the normal healthy fingerprint at the systemic level or in tissues from the diseased organ(s). By applying mass spectrometry and nuclear magnetic resonance as analytical platforms, metabolomics has been used for colorectal cancer phenotyping at different levels. The metabolic profile as a whole is a complex biomarker of diagnostic and prognostic value. Results are promising for the implementation of the method at the clinical level, but larger scale studies and extensive standardization of the pre-analytical phase are needed for a validated definition of the colorectal cancer signature.     

Usefulness of endoscopic ultrasonography with a microprobe in the diagnosis of aortoesophageal fistula

Aortoesophageal fistula (AEF) is very rare and is associated with a high mortality rate. AEF manifests with massive gastrointestinal bleeding and is difficult to diagnose from endoscopic findings and clinical features. We encountered a patient with an AEF that was promptly diagnosed by endoscopic ultrasonography (EUS) using a microprobe. A 58-year-old man was admitted to our hospital because of hematemesis. Endoscopic examination revealed a submucosal tumor (SMT)-like lesion 2 cm in diameter 25 cm from the dental arch. EUS with a 20-MHz microprobe revealed a blood vessel-like structure with hypoechoic flowing contents and a high echoic area suggestive of a thrombus protruding into the esophageal lumen. AEF resulting from a ruptured thoracic aortic aneurysm was suggested from the EUS findings and was definitely diagnosed by computed tomography. Graft replacement of the descending aorta was successfully performed. The patient is now in good health 6 years after the first admission. This is the first report of a case of AEF diagnosed by EUS with a microprobe.