Activation of the Cap'n'collar C pathway (Nrf2 pathway in vertebrates) signaling in insulin pathway compromised Drosophila melanogaster flies ameliorates the diabetic state upon pro-oxidant conditions.

The insulin pathway is a crucial central system for metabolism and growth. The Nrf2 signaling pathway functions to counteract oxidative stress. Here we sought to study the consequences of an oxidative stress challenge to insulin compromised and control adult flies of different ages, varying the activation state of the Nrf2 pathway in flies, the Cap'n'collar C pathway. For this, we employed two different pro-oxidative conditions: 3 % hydrogen peroxide or 20 mM paraquat laced in the food. In both cases, wild type (control) flies die within a few days, yet there are significant differences between males and females, and also within flies of different ages (seven versus thirty days old flies). We repeated the same conditions with young (seven days old) flies that were heterozygous for a loss-of-function mutation in Keap1. There were no significant differences. We then tested two hypomorphic viable conditions of the insulin pathway (heteroallelic combination for the insulin receptor and the S6 Kinase), challenged in the same way: Whereas they also die in the pro-oxidant conditions, they fare significantly better when heterozygous for Keap1, in contrast to controls. We also monitored locomotion in all of these conditions, and, in general, found significant differences between flies without and with a mutant allele (heterozygous) for Keap1. Our results point to altered oxidative stress conditions in diabetic flies. These findings suggest that modest activation of the Cap'n'collar C pathway may be a treatment for diabetic symptoms.

The insulin signaling pathway a century after its discovery: Sexual dimorphism in insulin signaling.

Since practically a century ago, the insulin pathway was discovered in both vertebrates and invertebrates, implying an evolutionarily ancient origin. After a century of research, it is now clear that the insulin signal transduction pathway is a critical, flexible and pleiotropic pathway, evolving into multiple anabolic functions besides glucose homeostasis. It regulates paramount aspects of organismal well-being like growth, longevity, intermediate metabolism, and reproduction. Part of this diversification has been attained by duplications and divergence of both ligands and receptors riding on a common general signal transduction system. One of the aspects that is strikingly different is its usage in reproduction, particularly in male versus female development and fertility within the same species. This review highlights sexual divergence in metabolism and reproductive tract differences, the occurrence of sexually "exaggerated" traits, and sex size differences that are due to the sexes' differential activity/response to the insulin signaling pathway.

Portal Thrombosis in Cirrhosis: Role of Thrombophilic Disorders.

In patients with liver cirrhosis the contribution of inherited and acquired prothrombotic disorders in the development of non-malignant portal vein thrombosis (PVT) is inconclusive. The purpose of this retrospective study was to examine the prevalence of thrombophilia in this setting at our center from January 2012 to November 2019. Tests included gene mutational analysis for Factor V Leiden, prothrombin G20210A, JAK2 (V617F), Calreticulin (CARL), in addition to activated protein C resistance, antithrombin III, protein C and S levels, and antiphospholipid antibodies. We included 77 patients, six of whom (7.8%) had a thrombophilic disorder: antiphospholipid syndrome in four patients, prothrombin gene mutation in one and factor V Leiden mutation in one. This latter patient had also been diagnosed with polycythemia vera years before PVT development. Complete thrombosis of the main portal vein and re-thrombosis after stopping anticoagulation were more frequent in patients with thrombophilia, but the rates of recanalization under anticoagulant therapy were similar among groups. No other difference was accounted between groups. The low prevalence of acquired and inherited thrombophilia found in patients with cirrhosis and PVT support testing for these disorders on an individual basis and avoiding universal screening to reduce costs and unwarranted testing.

Metal Accumulation by Jatropha curcas L. Adult Plants Grown on Heavy Metal-Contaminated Soil.

Jatropha curcas has the ability to phytoextract high amounts of heavy metals during its first months just after seeding. Notwithstanding, there is scarce information about metal uptake by adult J. curcas plants. To shed light on this issue, 4-year-old J. curcas L. plants were planted in a soil mixture of peat moss and mining soil (high metals content), and the biomass growth and metal absorption during 90 days were compared with those of plants growing in peat moss. The main metal found in the mining soil was Fe (31985 mg kg-1) along with high amounts of As (23717 mg kg-1). After the 90-day phytoremediation, the plant removed 29% of Fe and 44% of As from the soil mixture. Results revealed that J. curcas L. translocated high amounts of metals to its aerial parts, so that translocation factors were much higher than 1. Because of the high translocation and bioaccumulation factors obtained, J. curcas L. can be regarded as a hyperaccumulator plant. Despite the great capacity of J. curcas L. to phytoremediate heavy-metal-contaminated soils, the main drawback is the subsequent handling of the metal-contaminated biomass, although some potential applications have been recently highlighted for this biomass.

Endoscopic Gallbladder Drainage for Acute Cholecystitis

BACKGROUND/AIMS: Surgery is the mainstay of treatment for cholecystitis. However, gallbladder stenting (GBS) has shown promise in debilitated or high-risk patients. Endoscopic transpapillary GBS and endoscopic ultrasound-guided GBS (EUS-GBS) have been proposed as safe and effective modalities for gallbladder drainage. METHODS: Data from patients with cholecystitis were prospectively collected from August 2004 to May 2013 from two United States academic university hospitals and analyzed retrospectively. The following treatment algorithm was adopted. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and cystic duct stenting was initially attempted. If deemed feasible by the endoscopist, EUS-GBS was then pursued. RESULTS: During the study period, 139 patients underwent endoscopic gallbladder drainage. Among these, drainage was performed in 94 and 45 cases for benign and malignant indications, respectively. Successful endoscopic gallbladder drainage was defined as decompression of the gallbladder without incidence of cholecystitis, and was achieved with ERCP and cystic duct stenting in 117 of 128 cases (91%). Successful endoscopic gallbladder drainage was also achieved with EUS-guided gallbladder drainage using transmural stent placement in 11 of 11 cases (100%). Complications occurred in 11 cases (8%). CONCLUSIONS: Endoscopic gallbladder drainage techniques are safe and efficacious methods for gallbladder decompression in non-surgical patients with comorbidities.

Glucagonoma syndrome: a case report.

INTRODUCTION: Glucagonoma syndrome is a rare paraneoplastic phenomenon, with an estimated incidence of one in 20 million, characterized by necrolytic migratory erythema, hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, cheilitis, steatorrhea, diarrhea, venous thrombosis and neuropsychiatric disturbances in the setting of a glucagon-producing alpha-cell tumor of the pancreas. Necrolytic migratory erythema is the presenting manifestation in the majority of cases, so its early suspicion and correct diagnosis is a key factor in the management of the patient. CASE PRESENTATION: We present the case of a 70-year-old Caucasian woman with glucagonoma syndrome due to an alpha-cell tumor located in the tail of the pancreas, successfully treated with surgical resection. CONCLUSION: Clinicians should be aware of the unusual initial manifestations of glucagonoma. Early diagnosis allows complete surgical resection of the neoplasm and provides the only chance of a cure.