Prostate growth and inflammation

INTRODUCTION: There is emerging evidence that prostatic inflammation may contribute to prostate growth either in terms of hyperplastic (BPH) or neoplastic (PC) changes. Inflammation is thought to incite carcinogenesis by causing cell and genome damage, promoting cellular turnover. METHODS: We reviewed our personal experience and the international recent literature on the clinical data supporting a role of inflammation on BPH and PC growth and progression. RESULTS: BPH: Among those patients with self-reported prostatitis, 57% had a history of BPH. MTOPS study showed that men with inflammation had a significantly higher risk of BPH progression and acute urinary retention. We showed that the use of a COX-2 inhibitor in combination with a 5 alpha reductase inhibitor could increase the apoptotic index in BPH tissue. Prostate cancer: A PCR-based analysis of bacterial colonization in PC specimens and normal prostate tissue showed highly suggestive correlation of bacterial colonization and chronic inflammation with a diagnosis of PC. Evidence from genetic studies support the hypothesis that prostate inflammation may be a cause of prostate cancer. De Marzo proposed that proliferative inflammatory atrophy (PIA) is a precursor to PIN and cancer. CONCLUSION: The concept that inflammation can promote prostate growth either in terms of BPH and PC risk remains highly suggestive.     

The effects of tin (Sn) additions on the growth of spinach plants

An increase in bioavailable tin in the environment could result in bioaccumulation thereof in agricultural crops, and therefore, have adverse health consequences on humans that eat these crops. The aims of the current study were thus to assess the uptake of Sn by spinach plants, and the subsequent effects this will have on the uptake of Na, Zn, K, Ca, and Mg as well as the growth of spinach plants. Spinach plants were grown in sand culture and received tin at concentrations of 0.02, 0.2, 2 and 20 mg/L along with a nutrient solution. The uptake of tin at detectible concentrations only occurred at the highest concentrations (2 and 20 mg/L), and it was mostly retained in the roots of the plants. Tin additions also resulted in no visual toxicity symptoms, and might be beneficial to biomass production. Further field trials are needed to ensure that these experimental results remain true under field conditions.     

Identification of the archaeal NMN adenylyltransferase gene

Increasing evidence on the importance of fluctuations in NAD+ levels in the living cell is accumulating. Therefore a deeper knowledge on the regulation of coenzyme synthesis and recycling is required. In this context the study of NMN adenylyltransferase (EC 2.7.7. 1), a key enzyme in the NAD+ biosynthetic pathway, assumes a remarkable relevance. We have previously purified to homogeneity and characterized the protein from the thermophilic archaeon Sulfolobus solfataricus. The determination of partial sequence of the S. solfataricus enzyme, together with the recent availability of the genome sequence of the archaeon Methanococcus jannaschii allowed us, based on sequence similarity, to identify the M. jannaschii NMN adenylyltransferase gene. As far as we know from literature, this is the first report on the NMN adenylyltransferase gene.     

Flexible work hours, health and well-being in the European Union: preliminary data from a SALTSA project

Demand for flexible work hours (FWH) is increasing in Europe aimed at increasing the number of production hours on one hand, and, on the other, reducing individual working hours and/or increasing autonomy and control on them. In view of the lack of knowledge of the effects of FWH on health and safety, we started a pilot project, funded by the Joint Programme for Working Life Research in Europe (SALTSA), aimed at: a) comparing the most relevant national legislation and how the EU Directive 93/104 "concerning certain aspects of working time" has been implemented in the member States; b) reporting prevalence and trend of FWH in Europe according to the three EU Surveys on Working Conditions carried out in the last decade; c) collecting practical examples of innovative FWH; d) evaluating their impact on health and safety in relation to work sectors, job demands, social life, aging and gender. Consequent actions are going to include information and consultancy for pertinent authorities and social parties involved, as well as training programmes for Union officials and similar groups concerning the organisation of FWH according to ergonomic principles.     

Mixed inhibitions by methanol, furfural and acetic acid on xylitol production by Candida guilliermondii

Xylose production by Candida guilliermondii FTI 20037 was carried out in a synthetic medium in the presence of 0–100 g methanol l^–1, 0–0.7 g furfural l^–1 or 0–1.3 g acetic acid l^–1. Kinetic results show a mixed inhibition mechanism in all three cases. Maximum specific productivity and saturation constant for product formation were, in the absence of inhibition, 3.6 g_P g_X ^–1 h^–1 and 232 g_S l^–1, respectively, while the inhibition constants, K _i and K _i, were 17 and 50 g methanol l^–1, 0.62 and 7.0 g furfural l^–1, 0.69 and 3.5 g acetic acid l^–1, which suggests the following order of inhibition: furfural > acetic acid > methanol.     

Induction of indoleamine 2,3-dioxygenase in vascular smooth muscle cells by interferon-gamma contributes to medial immunoprivilege

Atherosclerosis and graft arteriosclerosis are characterized by leukocytic infiltration of the vessel wall that spares the media. The mechanism(s) for medial immunoprivilege is unknown. In a chimeric humanized mouse model of allograft rejection, medial immunoprivilege was associated with expression of IDO by vascular smooth muscle cells (VSMCs) of rejecting human coronary artery grafts. Inhibition of IDO by 1-methyl-tryptophan (1-MT) increased medial infiltration by allogeneic T cells and increased VSMC loss. IFN-gamma-induced IDO expression and activity in cultured human VSMCs was considerably greater than in endothelial cells (ECs) or T cells. IFN-gamma-treated VSMCs, but not untreated VSMCs nor ECs with or without IFN-gamma pretreatment, inhibited memory Th cell alloresponses across a semipermeable membrane in vitro. This effect was reversed by 1-MT treatment or tryptophan supplementation and replicated by the absence of tryptophan, but not by addition of tryptophan metabolites. However, IFN-gamma-treated VSMCs did not activate allogeneic memory Th cells, even after addition of 1-MT or tryptophan. Our work extends the concept of medial immunoprivilege to include immune regulation, establishes the compartmentalization of immune responses within the vessel wall due to distinct microenvironments, and demonstrates a duality of stimulatory EC signals versus inhibitory VSMC signals to artery-infiltrating T cells that may contribute to the chronicity of arteriosclerotic diseases.     

Homology modeling and deletion mutants of human nicotinamide mononucleotide adenylyltransferase isozyme 2: new insights on structure and function relationship

Nicotinamide mononucleotide adenylyltransferase (NMNAT) catalyzes the formation of NAD by means of nucleophilic attack by 5'-phosphoryl of NMN on the α-phosphoryl group of ATP. Humans possess three NMNAT isozymes (NMNAT1, NMNAT2, and NMNAT3) that differ in size and sequence, gene expression pattern, subcellular localization, oligomeric state and catalytic properties. Of these, NMNAT2, the least abundant isozyme, is the only one whose much-needed crystal structure has not been solved as yet. To fill this gap, we used the crystal structures of human NMNAT1 and NMNAT3 as templates for homology-based structural modeling of NMNAT2, and the resulting raw structure was then refined by molecular dynamics simulations in a water box to obtain a model of the final folded structure. We investigated the importance of NMNAT2's central domain, which we postulated to be dispensable for catalytic activity, instead representing an isozyme-specific control domain within the overall architecture of NMNAT2. Indeed, we experimentally confirmed that removal of different-length fragments from this central domain did not compromise the enzyme's catalytic activity or the overall tridimensional structure of the active site.     

Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure

Background  

Glaucoma is a common disease but its molecular etiology is poorly understood. It involves retinal ganglion cell death and optic nerve damage that is often associated with elevated intraocular pressure. Identifying genes that modify glaucoma associated phenotypes is likely to provide insights to mechanisms of glaucoma. We previously reported glaucoma in DBA/2J mice caused by recessive alleles at two loci, isa and ipd, that cause iris stromal atrophy and iris pigment dispersion, respectively. A approach for identifying modifier genes is to study the effects of specific mutations in different mouse strains. When the phenotypic effect of a mutation is modified upon its introduction into a new strain, crosses between the parental strains can be used to identify modifier genes. The purpose of this study was to determine if the effects of the DBA/2J derived isa and ipd loci are modified in strain AKXD-28/Ty.