A synthetic cell permeable antioxidant protects neurons against acute oxidative stress.

Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson's disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches.

Antitumour activity of the novel flavonoid Oncamex in preclinical breast cancer models.

Background: The natural polyphenol myricetin induces cell cycle arrest and apoptosis in preclinical cancer models. We hypothesised that myricetin-derived flavonoids with enhanced redox properties, improved cell uptake and mitochondrial targeting might have increased potential as antitumour agents.

Methods: We studied the effect of a second-generation flavonoid analogue Oncamex in a panel of seven breast cancer cell lines, applying western blotting, gene expression analysis, fluorescence microscopy and immunohistochemistry of xenograft tissue to investigate its mechanism of action.

Novel flavonoids as anti-cancer agents: mechanisms of action and promise for their potential application in breast cancer.

Flavonoids are a large group of ubiquitous polyphenolic secondary metabolites in plants with a wide range of properties, including a widely reported anti-cancer effect. The present review focuses on the different known mechanisms partaking in said anti-tumour effects, with particular emphasis on breast cancer. Their structure and reactivity allows flavonoids to work as antioxidant agents and phyto-oestrogens, modulating oestrogen signalling and metabolism to induce an overall anti-proliferative response.

Managing symptomatic drug-induced liver injury in HIV-hepatitis C virus-coinfected patients: a role for interferon.

Background: Human immunodeficiency virus (HIV)-infected patients with hepatitis C virus (HCV) coinfection are at increased risk for drug-induced liver injury (DILI) compared with patients with HIV infection alone. The mechanism underlying this observation is unknown. We hypothesized that interferon (IFN) would induce biochemical improvement through its anti-inflammatory properties and thereby facilitate the reintroduction of antiretroviral therapy (ART) in patients with DILI.

Phloem-based resistance to green peach aphid is controlled by Arabidopsis PHYTOALEXIN DEFICIENT4 without its signaling partner ENHANCED DISEASE SUSCEPTIBILITY1.

Green peach aphid (GPA) Myzus persicae (Sülzer) is a phloem-feeding insect with an exceptionally wide host range. Previously, it has been shown that Arabidopsis thaliana PHYTOALEXIN DEFICIENT4 (PAD4), which is expressed at elevated levels in response to GPA infestation, is required for resistance to GPA in the Arabidopsis accession Columbia. We demonstrate here that the role of PAD4 in the response to GPA is conserved in Arabidopsis accessions Wassilewskija and Landsberg erecta.

Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients.

Background: We conducted a study to determine the prevalence and factors associated with hepatic steatosis in human immunodeficiency virus (HIV)-seropositive patients with hepatitis C and to investigate whether steatosis is associated with liver fibrosis.

Methods: Retrospective chart reviews were conducted in 4 hospitals that serve community-based and incarcerated HIV-infected patients who had undergone a liver biopsy for evaluation of hepatitis C virus (HCV) infection during the period of 2000-2003. Demographic characteristics and medication and laboratory data were collected from the time of the biopsy.

The Cables gene on chromosome 18Q regulates colon cancer progression in vivo.

Early events involved in the pathogenesis of colorectal cancer include mutations in the Adenomatous Polyposis Coli tumor-suppressor gene and oncogenic KRAS mutations. Later events include deletions on chromosome 18q, which are observed in a high proportion of colorectal cancers. However, the important tumor suppressor genes targeted by these deletions have not been fully defined.

Miscellaneous conditions of the appendix.

A variety of miscellaneous conditions affect the appendix, both as incidental findings and as causes of clinical signs and symptoms that often mimic appendicitis. Congenital abnormalities of the appendix are rare; the two most commonly reported are congenital absence and appendiceal duplication. Diverticular disease may be an incidental finding, but when inflamed, can be clinically confused with appendicitis.

The cytoplasmic dot staining pattern is detected in a subgroup of patients with primary biliary cirrhosis.

Objective: To determine the clinical significance of the cytoplasmic dot anti-"nuclear" antibody (ANA) staining pattern.

Methods: We describe a patient with fatigue, arthralgias, elevated serum transaminase, and antibodies staining 5-20 cytoplasmic dots in HEp-2 cells. A liver biopsy revealed the presence of Stage III primary biliary cirrhosis (PBC).

Overexpression of cyclin D1 in pancreatic beta-cells in vivo results in islet hyperplasia without hypoglycemia.

Cyclin D1 can stimulate proliferation by driving cells from the G1 into the S-phase of the mammalian cell cycle. Previous animal studies have implicated the G1-S transition as a key regulatory checkpoint governing the proliferation of pancreatic islet cells. We expressed cyclin D1 in the beta-cells of mice and islet hyperplasia developed in a time-dependent manner.

Autoimmune hepatitis with centrilobular necrosis.

Autoimmune hepatitis (AIH) is usually a chronic portal-based hepatitis with prominent plasma cells. Although necroinflammatory activity throughout the lobule is described, centrilobular necrosis (CN) is only rarely the predominant pattern of injury. Recognition of the possibility of AIH in zone 3 hepatitis will lead to prompt steroid therapy and may avert cirrhosis.

Treatment of bleeding colonic diverticula by endoscopic band ligation: an in-vivo and ex-vivo pilot study.

Background And Study Aims: Angiographic and surgical therapy are standards of care for persistent diverticular bleeding. Colonoscopic intervention using epinephrine injection, multipolar electrocautery, and placement of an Endoclip has not gained widespread acceptance due to concerns about complications,and the widespread management of severe lower gastrointestinal bleeding by surgeons and interventional radiologists. The utility of colonoscopic band ligation for control of diverticular bleeding was evaluated both in vivo and ex vivo.

Appendiceal mucinous neoplasms: a clinicopathologic analysis of 107 cases.

The classification of appendiceal mucinous tumors is controversial and terminology used for them inconsistent, particularly when they lack overtly malignant features but are associated with extra-appendiceal spread. We reviewed 107 appendiceal mucinous neoplasms and classified them as low-grade appendiceal mucinous neoplasm (LAMN) (n = 88), mucinous adenocarcinomas (MACAs) (n = 16), or discordant (n = 3) based on architectural and cytologic features. LAMNs were characterized by a villous or flat proliferation of mucinous epithelium with low-grade atypia.

Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial.

Background: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis.

Aim: To evaluate repifermin for the treatment of active ulcerative colitis.

Methods: Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial.

Prevention of pancreatic fistula with a new synthetic, absorbable sealant: evaluation in a dog model.

Background: Pancreatic fistula complicates up to 15% to 25% of pancreatic resections, especially with soft, normal pancreas, and is most common after distal pancreatectomy. A new synthetic, absorbable hydrogel sealant has recently been developed and tested for sealing of human aorta, bronchi, and dura; it is FDA approved as a lung sealant in humans. Our objective was to test the efficacy of the sealant in preventing pancreatic leaks in a dog model of distal pancreatectomy.

Pancreatic neuroendocrine neoplasms: a current summary of diagnostic, prognostic, and differential diagnostic information.

Pancreatic endocrine tumors (PETs) continue to be challenging diagnostic and prognostic lesions in surgical pathology and clinical medicine. These neoplasms can be graded into 1 of 3 tiers, based on histologic characteristics in likeness to epithelial neuroendocrine tumors in other anatomic sites. However, grade 1 tumors are by far the most common and are the most difficult to prognosticate.

Treatment of recurrent allograft dysfunction with intravenous hematin after liver transplantation for erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthetic pathway in which toxic levels of protoporphyrins often precipitate in the liver, leading to cirrhosis, liver failure, and the need for liver transplantation (OLT). Because the underlying enzyme defect in EPP is bone marrow derived, the risk for recurrent EPP allograft dysfunction is high. Although plasmapheresis may ameliorate acute allograft disease, strategies to maintain disease remission are needed.

Combined liver and kidney transplantation in a patient with sickle cell disease.

Sickle cell intrahepatic cholestasis is a potentially fatal end-organ complication of sickle cell anemia. Renal involvement in sickle cell anemia is common, and in some cases, can present as acute renal failure. Although renal transplants have been performed in patients with sickle cell anemia since the late 1960s and a number of liver transplants have been recently performed for these complications, there has not been experience with dual organ transplantation for sickle cell anemia-related complications.

An EDS1 orthologue is required for N-mediated resistance against tobacco mosaic virus.

In Arabidopsis, EDS1 is essential for disease resistance conferred by a structural subset of resistance (R) proteins containing a nucleotide-binding site, leucine-rich-repeats and amino-terminal similarity to animal Toll and Interleukin-1 (so-called TIR-NBS-LRR proteins). EDS1 is not required by NBS-LRR proteins that possess an amino-terminal coiled-coil motif (CC-NBS-LRR proteins). Using virus-induced gene silencing (VIGS) of a Nicotiana benthaminana EDS1 orthologue, we investigated the role of EDS1 in resistance specified by structurally distinct R genes in transgenic N.

Rapidly progressive fibrosing cholestatic hepatitis--hepatitis C virus in HIV coinfection.

Fibrosing cholestatic hepatitis (FCH) is a severe and progressive form of liver dysfunction seen in organ transplant recipients infected with hepatitis B virus or hepatitis C virus (HCV) and has been attributed to cytopathic liver injury. To date, no case of FCH due to HCV has been reported in HIV-positive individuals. We describe two cases of HCV-induced FCH in two patients coinfected with HIV, culminating in rapidly progressive liver failure and death.