Reconstituted halogenated hydrocarbon pesticide and pollutant mixtures found in human tissues: effects on the immature male Wistar rat after short-term exposure

Halogenated hydrocarbon insecticides and polychlorinated biphenyl (PCB) mixtures are routinely detected as residues in human adipose tissue, serum, and milk. Based on average values observed in analytical studies, reconstituted halogenated hydrocarbon pesticide mixtures and PCB mixtures were prepared and administered to immature male Wistar rats. The mixtures were administered at dose levels which approximate the concentrations which would be absorbed by an infant suckling for 180 days (low dose, L), and at three higher dose levels (2 X L, 10 X L, and 100 X L). The pesticide mixture contained isomeric hexachlorocyclohexanes, dieldrin, heptachlor epoxide, oxychlordane, trans-nonachlor, hexachlorobenzene, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane, and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene; the reconstituted PCB mixture contained 13 of the major congeners which have been identified in human milk samples. Administration of the L dose level of the pesticide (0.95 mg/kg), PCB (0.45 mg/kg), and pesticide plus PCB mixture (0.95 + 0.45 mg/kg, respectively) in corn oil on days 1 and 3 did not significantly alter hepatic drug-metabolizing enzyme activities or elicit any observable pathological damage 6 days after the first exposure. In contrast, administration of the higher dose levels of this mixture elicited a dose-dependent induction of several hepatic drug-metabolizing enzymes. Moreover, despite the short duration of exposure to these chemicals, the rats treated with the higher doses (10 X L and 100 X L) of these mixtures exhibited mild alterations in thyroid architecture, changes in hepatocellular nuclei including variations in chromatin distribution, vesiculation of larger nuclei, and frequent appearance of pyknotic shrunken nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phytotherapeutic approach to alcohol dependence: New old way?

Alcohol abuse and dependence represent a worldwide problem from both medical and social points of view. In Italy it is estimated that there are about one million alcohol-dependent subjects. The pharmacological treatment of patients with alcohol dependence plays a key role in order to achieve alcohol abstinence and prevent relapse. At present, the possible utility of the complementary medicines in the treatment of alcohol dependence is controversial. In the last years, pre-clinical and clinical data from traditional medicines suggest that novel pharmacological approaches for treatment of alcoholism and alcohol abuse may stem from natural substances. The present review summarizes the findings of the effects of phytotherapy in alcohol addiction.     

Development and characterization of a novel bioactive polymer with antibacterial and lysozyme‐like activity

The development and characterization of a novel bioactive polymer based on the immobilization of glucose oxidase enzyme (GOx) in a polyvinyl alcohol (PVA) film showing antibacterial activity is presented. The PVA‐GOx composite material was extensively characterized by UV‐vis, X‐ray Photoelectron (XPS) spectroscopy and by Fourier Transform Infrared (FTIR) spectroscopy to verify the preservation of enzyme structural integrity and activity. The antimicrobial activity of this composite material against Escherichia coli and Vibrio alginolyticus was assessed. Furthermore the lysozyme‐like activity of PVA‐GOx was highlighted by a standard assay on Petri dishes employing Micrococcus lysodeikticus cell walls. The findings from this study have implications for future investigations related to the employment of PVA‐GOx system as a composite material of pharmaceutical and technological interest. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 461–470, 2014.     

The Inflammasome Pyrin Contributes to Pertussis Toxin-Induced IL-1β Synthesis,Neutrophil Intravascular Crawling and Autoimmune Encephalomyelitis

Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), a bacterial virulence factor commonly used as an adjuvant to promote EAE, but whose mechanism of action is unclear. We have reported that PTX triggers an IL-6-mediated signaling cascade that increases the number of leukocytes that patrol the vasculature by crawling on its luminal surface. In the present study, we examined this response in mice lacking either TLR4 or inflammasome components and using enzymatically active and inactive forms of PTX. Our results indicate that PTX, through its ADP-ribosyltransferase activity, induces two series of events upstream of IL-6: 1) the activation of TLR4 signaling in myeloid cells, leading to pro-IL-1β synthesis; and 2) the formation of a pyrin-dependent inflammasome that cleaves pro-IL-1β into its active form. In turn, IL-1β stimulates nearby stromal cells to secrete IL-6, which is known to induce vascular changes required for leukocyte adhesion. Without pyrin, PTX does not induce neutrophil adhesion to cerebral capillaries and is less effective at inducing EAE in transgenic mice with encephalitogenic T lymphocytes. This study identifies the first microbial molecule that activates pyrin, a mechanism by which infections may influence MS and a potential therapeutic target for immune disorders.     

A mutant allele of BARA/LIN-9 rescues the cdk4-/- phenotype by releasing the repression on E2F-regulated genes

It has been proposed that C. elegans LIN-9 functions downstream of CDK4 in a pathway that regulates cell proliferation. Here, we report that mammalian BARA/LIN-9 is a predominantly nuclear protein that inhibits cell proliferation. More importantly, we demonstrate that BARA/LIN-9 also acts downstream of cyclin D/CDK4 in mammalian cells since (i) its antiproliferative effect is partially blocked by coexpression of cyclin D1, and (ii) a mutant form that lacks the first 84 amino acids rescues several phenotypic alterations observed in mice null for cdk4. Interestingly, mutation of BARA/LIN-9 restores the expression of E2F target genes in CDK4 null MEFs, indicating that the wild-type protein plays a role in the expression of genes required for the G1/S transition.     

Lactate production yield from engineered yeasts is dependent from the host background, the lactate dehydrogenase source and the lactate export

Background  

Metabolic pathway manipulation for improving the properties and the productivity of microorganisms is becoming a well established concept. For the production of important metabolites, but also for a better understanding of the fundamentals of cell biology, detailed studies are required. In this work we analysed the lactate production from metabolic engineered Saccharomyces cerevisiae cells expressing a heterologous lactate dehydrogenase (LDH) gene. The LDH gene expression in a budding yeast cell introduces a novel and alternative pathway for the NAD⁺ regeneration, allowing a direct reduction of the intracellular pyruvate to lactate, leading to a simultaneous accumulation of lactate and ethanol.