Characterization of visual manifestations and identification of risk factors for permanent vision loss in patients with giant cell arteritis

Clinical Rheumatology - Permanent vision loss (PVL) is a feared complication and a leading cause of morbidity in giant cell arteritis (GCA). The objective of this study is to describe visual...     

Muscle system of Diplodiscus subclavatus (Trematoda: Paramphistomida) cercariae,pre-ovigerous,and ovigerous adults

The musculature of cercariae, pre-ovigerous, and ovigerous adults of Diplodiscus subclavatus was studied by means of TRITC-conjugated phalloidin staining of filamentous actin and confocal scanning laser microscopy. The body wall appears to include four muscle layers as follows: circular, outer longitudinal, diagonal, and inner longitudinal. Two layers of longitudinal muscle fibers are arranged in different modes due to the secondary transformed paramphistomid body construction. The organization of the acetabulum turned out to be more complex than ever described, with a radial layer, two layers of circular, two layers of meridional, an additional starry layer of muscle fibers, as well as a few separate muscle layers of the accessory sucker. Within the pharynx, I found a group of alar muscle fibers, never described before for any paramphistomids, and some morphological features which were not considered to be characteristic for D. subclavatus (namely—the middle semicircular layer and the transverse muscle fibers in the pre-sphincteric space). No significant reorganizations of the somatic musculature occur throughout the development from the cercaria to the ovigerous adult worm, so the metamorphosis goes in the manner of completion. The cercarial tail includes a layer of circular muscle fibers and a longitudinal muscle layer beneath. The latter consists of two medial longitudinal bundles of smooth muscle fibers and two lateral longitudinal bands of obliquely striated muscle fibers which are partially divided in halves.     

Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation

BACKGROUND Arachidyl amido cholanoic acid(Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1) protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis. In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH), 52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c, an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model [induced with a 0.1% methionine and choline deficient diet(0.1 MCD)] after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20 μmol/L Aramchol or vehicle for 48 h. Subsequently, analyses were performed including Western blot, proteomics by mass spectrometry, and fluxomic analysis with ~(13)C-uniformly labeled glucose. For the in vivo part of the study, male C57 BL/6 J mice were randomly fed a control or 0.1 MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk. Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes. This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA) synthesis and oxidation [PACCα/β(S79), SCD1, CPT1A/B, HADHA, and HADHB], oxidative phosphorylation(NDUFA9, NDUFB11, NDUFS1, NDUFV1, ETFDH, and UQCRC2), tricarboxylic acid(TCA) cycle(MDH2, SUCLA2, and SUCLG2), and ribosome(P-p70S6K[T389] and P-S6[S235/S236]). Flux experiments with ~(13)C uniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes, as indicated by the increase in the number of rounds that malate remained in the TCA cycle. Finally, liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1 MCD fed mice in a dose-dependent manner, showing normalization of glucose, G6P, F6P, UDP-glucose, and Rbl5 P/Xyl5 P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1, which in turn activate FA β-oxidation and oxidative phosphorylation.     

Hypnotic enhancement of creative drawing

A hypnotically based intervention to enhance creativity in drawing was evaluated in a controlled study. Participants were randomly assigned to either a hypnotic treatment or a nonhypnotic (task-motivational) control treatment. Subjects drew a standard still-life tableau twice. The first drawing involved no special instructions and provided a baseline measure of creativity in drawing. The second drawing was completed after the creativity-enhancement procedure. The drawings were rated blindly on several dimensions of artistic creativity. Hypnotizability, absorption, and debriefing measures were also administered. Results indicated that the hypnotic procedure had significantly greater effects on creativity in drawing. However, there were no significant main effects or interactions involving hypnotizability or absorption. Hypnotic and task-motivational groups did not differ on debriefing measures regarding their experience.     

Phase I-II trial of gene therapy with tag-7 modified autologous tumor cells in patients with metastatic solid tumors

A prospective (phase I-II) trial was undertaken to study the efficacy and toxicity of gene therapy with tag 70-modified autologous tumor cells in 32 patients with metastatic renal cell carcinoma (RC) (5) and melanoma (MBL) (27) treated at the Institute's Clinic (2001-2003). Resected material was reduced to cell culture, which was transfected with tag 70 gene and devitalized by irradiation. Immune blotting was used for gene expression. Clinical and immunological effectiveness was evaluated in 22 patients (MBL--17 and RC--5) who received 1-6 injections (3 on the average). Full course of vaccination was given to 8 (MBL--6 and RC--2). No complete or partial response was reported while least regression (50%) was registered in a case of RC metastatic to the lung. According to CT and ultrasound evidence, stabilization was achieved in 5 (23.8%) (MBL--4 and RC--1). Relapse-free period was 6.5+/-3.5 months beginning from the start of treatment. The vaccine was well tolerated while DHT reaction was observed in 47.6% (10 out of 17) of primary immunized patients. A trend of increased content of T- and B-cells in peripheral blood and intensified functional activity was established.     

Anthrax toxin induces hemolysis: an indirect effect through polymorphonuclear cells

Anthrax toxin can induce hemolysis in the presence of polymorphonuclear cells (PMNs), an activity primarily mediated by protective antigen, with synergic effects provided by lethal factor and edema factor. Lethal factor and edema factor, individually or in combination, are incapable of lysing red blood cells. The requirement for the presence of PMNs indicates that hemolysis associated with Bacillus anthracis infection is indirect rather than direct, as observed in many other bacterial infections.     

Chemical sensing in mammalian host–bacterial commensal associations

The mammalian gastrointestinal (GI) tract is colonized by a complex consortium of bacterial species. Bacteria engage in chemical signaling to coordinate population-wide behavior. However, it is unclear if chemical sensing plays a role in establishing mammalian host–bacterial commensal relationships. Enterohemorrhagic Escherichia coli (EHEC) is a deadly human pathogen but is a member of the GI flora in cattle, its main reservoir. EHEC harbors SdiA, a regulator that senses acyl-homoserine lactones (AHLs) produced by other bacteria. Here, we show that SdiA is necessary for EHEC colonization of cattle and that AHLs are prominent within the bovine rumen but absent in other areas of the GI tract. We also assessed the rumen metagenome of heifers, and we show that it is dominated by Clostridia and/or Bacilli but also harbors Bacteroidetes. Of note, some members of the Bacteroidetes phyla have been previously reported to produce AHLs. SdiA-AHL chemical signaling aids EHEC in gauging these GI environments, and promotes adaptation to a commensal lifestyle. We show that chemical sensing in the mammalian GI tract determines the niche specificity for colonization by a commensal bacterium of its natural animal reservoir. Chemical sensing may be a general mechanism used by commensal bacteria to sense and adapt to their mammalian hosts. Additionally, because EHEC is largely prevalent in cattle herds, interference with SdiA-mediated cattle colonization is an exciting alternative to diminish contamination of meat products and cross-contamination of produce crops because of cattle shedding of this human pathogen.