Effects of Heavy Metals Artificial Contamination on Porcellio laevis (Latreille, 1804) (Crustacea: Isopoda: Oniscidea)

Bulletin of Environmental Contamination and Toxicology - This study aimed at determining the competition of cadmium (Cd), lead (Pb), zinc (Zn) and copper (Cu) on their assimilation, on the food...     

Panel review of anaplastic oligodendroglioma from European Organization For Research and Treatment of Cancer Trial 26951: assessment of consensus in diagnosis, influence of 1p/19q loss, and correlations with outcome

The diagnosis of anaplastic oligodendroglioma (AOD) or anaplastic oligoastrocytoma (AOA) is subject to interobserver variation. The aim of this study was to estimate consensus in typing and grading of these tumors using tumor material collected in a large prospective randomized phase III study and to correlate the consensus diagnosis with the 1p/19q status of the tumors and the clinical outcome. The available pathology material of the first 150 patients, randomized into the European Organization for Research and Treatment of Cancer Trial 26951, was reviewed by an independent panel of 9 neuropathologists. The presence of deletions of 1p and 19q was assessed by fluorescence in situ hybridization with locus-specific probes. The panel reached consensus on the diagnosis of AOD in 52% of the tumors that had been diagnosed as AOD by the local pathologists, whereas only 8% of the local diagnosis of AOA was confirmed with consensus. The concordance on the panel diagnosis of AOD was high (intraclass correlation = 86%). The survival curves for AOD with 1p/19q loss, AOD without these losses, and AOA without 1p/19q loss ran separately in this order. The absence of necrosis and the presence of endothelial abnormalities were correlated with better outcomes. In multivariate analysis, patients' age, 1p/19q loss, and necrosis were identified as independent prognostic factors.     

Distribution of HLA-B*27 subtypes in Tunisians and their association with ankylosing spondylitis

ObjectiveThe human leukocyte antigen HLA-B27 is a class I antigen of the major histocompatibility complex strongly associated with ankylosing spondylitis (AS) and other related spondyloarthropathies (SpAs). The mechanism of this association remains unknown. HLA-B27 is a serologic specificity that represents a family of at least 25 different HLA-B27 alleles (2701–2725). These alleles are closely related by nucleotide sequence homology, but differ in ethnic distribution. The purpose of the present study is to investigate the distribution of HLA-B27 alleles in healthy controls and in patients with ankylosing spondylitis (AS).MethodsWe selected 160 HLA-B27-positive individuals (39 controls and 121 patients with ankylosing spondylitis). Typing of HLA-B27, and Cw alleles were performed by polymerase chain reaction amplification with sequence specific primers (PCR–SSP), and by serological typing (microlymphocytotoxicity).ResultsSeven B27 subtypes were identified: B*2702, 03, 04, 05, 07, 09 and B*2714. The distribution of these alleles in the population of patients was B*2702 (47.1%) and B*2705 (47.1%). These subtypes were also detected in 16 (41%) and 16 (41%), respectively of the 39 control subjects. HLA-B*2707 was detected in 4 (3.31%) patients and in 3 (7.6%) controls. B*2704, 09 and B*2714 were relatively rare and were detected in one subject each. No significant differences were noticed in the frequencies and distribution of HLA-B27 alleles between patients and controls.ConclusionsOur results show a restricted number of HLA B27 subtypes associated with AS. B*2702 and B*2705 were equally common in patients and controls. The most prominent B27/Cw haplotypes in the patient groups and controls were B*2702/Cw02022 and B*2705/Cw02022.     

Pathophysiology of sepsis--will the basic research contribute to the improvement of outcome in clinical sepsis?

In this decade, the molecular mechanism of sepsis has been strikingly clarified. Especially, the identification of toll-like receptors as the pivotal molecules for the recognition of the stimulation of the inflammatory products of microorganisms has contributed to the elucidation of intracellular signaling pathways which result in severe systemic inflammatory response in sepsis. The production and release of a variety of pro-inflammatory mediators have been found to be associated with severe systemic inflammation and multiple organ dysfunction syndrome (MODS). In the pathophysiology of the development of MODS in sepsis, the disturbance of peripheral microcirculation, the insult of tissues and cells by leukocytes and activated complements and the augmentation of the disorder of fibrinolytic and coagulation systems, which often results in the outbreak of disseminated intravascular coagulopathy (DIC), will be critically involved. Despite of the advance in the basic research regarding molecular pathophysiology of sepsis, sepsis is still accompanied by high mortality in clinical settings. Almost all clinical trials targeting sepsis-associated mediators have failed, except the substitution therapy of activated protein C. However, further trials based on the basic findings, including the therapies targeting the multiple mediators, will contribute to the improvement of outcome of clinical sepsis. ple organ dysfunction syndrome (MODS), pro-inflammatory mediator, disseminated intravascular coagulopathy (DIC).     

Meriolins, a new class of cell death inducing kinase inhibitors with enhanced selectivity for cyclin-dependent kinases

Protein kinases represent promising anticancer drug targets. We describe here the meriolins, a new family of inhibitors of cyclin-dependent kinases (CDK). Meriolins represent a chemical structural hybrid between meridianins and variolins, two families of kinase inhibitors extracted from various marine invertebrates. Variolin B is currently in preclinical evaluation as an antitumor agent. A selectivity study done on 32 kinases showed that, compared with variolin B, meriolins display enhanced specificity toward CDKs, with marked potency on CDK2 and CDK9. The structures of pCDK2/cyclin A/variolin B and pCDK2/cyclin A/meriolin 3 complexes reveal that the two inhibitors bind within the ATP binding site of the kinase, but in different orientations. Meriolins display better antiproliferative and proapoptotic properties in human tumor cell cultures than their parent molecules, meridianins and variolins. Phosphorylation at CDK1, CDK4, and CDK9 sites on, respectively, protein phosphatase 1alpha, retinoblastoma protein, and RNA polymerase II is inhibited in neuroblastoma SH-SY5Y cells exposed to meriolins. Apoptosis triggered by meriolins is accompanied by rapid Mcl-1 down-regulation, cytochrome c release, and activation of caspases. Meriolin 3 potently inhibits tumor growth in two mouse xenograft cancer models, namely, Ewing's sarcoma and LS174T colorectal carcinoma. Meriolins thus constitute a new CDK inhibitory scaffold, with promising antitumor activity, derived from molecules initially isolated from marine organisms.     

Effects of β‐aminoisobutyric acid on leptin production and lipid homeostasis: mechanisms and possible relevance for the prevention of obesity

β‐Aminoisobutyric acid (BAIBA) is a catabolite of thymine and antiretroviral thymine analogues AZT and d4T. We recently discovered that this β‐amino acid is able to enhance fatty acid oxidation and reduce body weight in mice through an increased production of leptin by the white adipose tissue (WAT). Furthermore, BAIBA could have favourable effects on nonalcoholic steatohepatitis in a leptin‐independent manner. In the present review, we shall recall the circumstances that led us to discover the effects of BAIBA on body fat mass and lipid homeostasis. In addition, we put forward several hypothetical mechanisms whereby BAIBA could enhance leptin secretion by WAT and present some anti‐inflammatory effects in the liver. We also discuss in this review (i) the deleterious impacts caused by the absence of, or low leptin expression on lipid homeostasis and body weight in humans and animals and (ii) recent data from other investigators suggesting that increasing leptin levels and/or responsiveness may be indeed an attractive pharmacological strategy in order to prevent (and/or treat) obesity, at least in some individuals.     

Estimation of Ochratoxin A in human blood of healthy Tunisian population

Human exposure to Ochratoxin A (OTA) has been investigated in many Mediterranean countries, where OTA was found with a higher frequency in foodstuffs and blood samples. The aim of this study was to assess OTA concentrations in human blood serum in Tunisia and to evaluate the impact of several factors (age, origin, sex) on these prevalence reference values. One hundred and seven blood serum samples from healthy subjects were analyzed using a solid-phase extraction linked to a high-performance liquid chromatography (HPLC) method. OTA values ranged from 0 to 3.43 ng/mL with a mean value of 0.49±0.67 ng/mL. OTA levels were higher in the Sahal group. Our results reflect OTA concentration previously detected for human blood in Tunisia. Origin, but not age and sex, may affect the OTA reference values.