Protective effects of resveratrol against oxidative/nitrative modifications of plasma proteins and lipids exposed to peroxynitrite

The protective effects of resveratrol (3, 4', 5-trihydroxystilbene; present naturally in different plants) against the oxidative/nitrative damage of human plasma proteins induced by peroxynitrite (ONOO-) were studied and compared with those of deferoxamine (DFO; a natural siderophore isolated from Streptomyces pilosus), which is a typical and well-known antioxidant. We also studied the effect of ONOO- on plasma lipid peroxidation and the role of tested antioxidants in this process. ONOO- at the used concentrations (0.01-1 mM) showed toxicity to human plasma components. Exposure of plasma to ONOO- (0.1 mM) resulted in an increase of the level of carbonyl groups and nitrotyrosine residues in plasma proteins (approximately 4-fold and 76-fold, respectively) and in a distinct augmentation of lipid peroxidation (approximately 2-fold). In the presence of 0.1-mM resveratrol, a distinct decrease of carbonyl group formation and tyrosine nitration in plasma proteins caused by 0.1-mM ONOO- was observed (by approximately 70% and 65%, respectively). Addition of 0.1-mM DFO to plasma also distinctly reduced the level of carbonyl groups and nitrotyrosines caused by 0.1-mM ONOO- (by approximately 50% and 60%, respectively). Moreover, these antioxidants also inhibited plasma lipid peroxidation induced by ONOO- (0.1 mM). The obtained results indicate that in vitro resveratrol, like well-known antioxidant DFO, has inhibitory effects on ONOO- -mediated oxidation of proteins and lipids in human plasma.     

Structure of the rhodopsin dimer: a working model for G-protein-coupled receptors

G-protein-coupled receptors (GPCRs) participate in virtually all physiological processes. They constitute the largest and most structurally conserved family of signaling molecules. Several class C GPCRs have been shown to exist as dimers in their active form and growing evidence indicates that many, if not all, class A receptors also form dimers and/or higher-order oligomers. High-resolution crystal structures are available only for the detergent-solubilized light receptor rhodopsin (Rho), the archetypal class A GPCR. In addition, Rho is the only GPCR for which the presumed higher-order oligomeric state has been demonstrated, by imaging native disk membranes using atomic force microscopy (AFM). Based on these data and the X-ray structure, an atomic model of Rho dimers has been proposed, a model that is currently scrutinized in various ways. AFM has also been used to measure the forces required to unfold single Rho molecules, thereby revealing which residues are responsible for Rho's stability. Recent functional analyses of fractions from solubilized disk membranes revealed that higher-order Rho oligomers are the most active species. These and other results have enhanced our understanding of GPCR structure and function.     

Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat and acrocentric heterochromatin in two families with chromosomal translocations

We report clinical findings and molecular cytogenetic analyses for two patients with translocations [t(14;17)(p12;p12) and t(15;17)(p12;p13.2)], in which the chromosome 17 breakpoints map at a large low-copy repeat (LCR) and a breakage-prone TRE-2 (USP6) oncogene, respectively. In family 1, a 6-year-old girl and her 5-year-old brother were diagnosed with mental retardation, short stature, dysmorphic features, and Charcot-Marie-Tooth disease type 1A (CMT1A). G-banding chromosome analysis showed a der(14)t(14;17)(p12;p12) in both siblings, inherited from their father, a carrier of the balanced translocation. Chromosome microarray and FISH analyses revealed that the PMP22 gene was duplicated. The chromosome 17 breakpoint was mapped within an ∼383 kb LCR17pA that is known to also be the site of several breakpoints of different chromosome aberrations including the evolutionary translocation t(4;19) in Gorilla gorilla. In family two, a patient with developmental delay, subtle dysmorphic features, ventricular enlargement with decreased periventricular white matter, mild findings of bilateral perisylvian polymicrogyria and a very small anterior commissure, a cryptic duplication including the Miller–Dieker syndrome region was identified by chromosome microarray analysis. The chromosome 17 breakpoint was mapped by FISH at the TRE-2 oncogene. Both partner chromosome breakpoints were mapped on the short arm acrocentric heterochromatin within or distal to the rRNA cluster, distal to the region commonly rearranged in Robertsonian translocations. We propose that TRE-2 together with LCR17pA, located ∼10 Mb apart, also generated the evolutionary gorilla translocation t(4;19). Our results support previous observations that the USP6 oncogene, LCRs, and repetitive DNA sequences play a significant role in the origin of constitutional chromosome aberrations and primate genome evolution.     

Evaluation of the therapeutic benefits in relation to the extent of surgery in patients with differentiated thyroid carcinoma

INTRODUCTION: Evaluation of the therapeutic benefits in relation to the stage of thyroid cancer and to the extent of surgery and the risk of postoperative complications. MATERIAL AND METHODS: Retrospective analysis of differentiated thyroid carcinoma (DTC) patients staged T1M0 versus T2-T4M0 was performed. All of them were treated or diagnosed in Institute of Oncology in Gliwice between 1986-1998. Previously they were operated in various surgical centers all-over Poland. The risk of death, local relapse and postoperative complications were analyzed using the decisiontree model to evaluate the therapeutic benefits. RESULTS: The recurrent laryngeal nerve injury (transient or permanent) was observed in retrospective analysis in 21% of patients, while postoperative hyperparathyroidism in 15.8%. The analysis of the therapeutic benefit index showed no advantage of total thyroidectomy in the T1M0 group (0.96 vs. 0.98 in patients treated by less than total thyroidectomy). The advantage of radical surgery was confirmed in T2-T4M0 group. The therapeutic benefit index was 0.92 in patients treated by total thyroidectomy and 0.69 in those who received less extensive operation. CONCLUSIONS: The analysis of therapeutic benefits confirmed the limit of 1 cm tumor diameter between less extensive surgery and total thyroidectomy. It showed that total thyroidectomy brings a significant therapeutic benefits in patients in > T1M0 stage. The improvement of overall survival and decrease of local relapse far outweigh the disadvantages related to postoperative complications.     

Influence of pinealectomy and long-term melatonin administration on bone metabolism in orchidectomized rats

INTRODUCTION: The aim of the study was to demonstrate whether pinealectomy and long-term MEL administration can affect bone metabolism (as evaluated on the basis of serum concentrations of PICP and ICTP) in orchidectomized rats. MATERIAL AND METHODS: The study included 248 adult male Wistar rats; 6 remained intact, 120 were orchidectomized (Orch), and the remaining ones underwent a sham operation (SOrch). Two weeks after surgery, the rats were divided into 8 groups: 1) SOrch + SPx; 2) SOrch + SPx + MEL; 3) Orch + SPx; 4) Orch + SPx + MEL; 5) SOrch + Px; 6) SOrch + Px + MEL; 7) Orch + Px; 8) Orch + Px + MEL. Animals from 5(th), 6(th), 7(th) and 8(th) groups were pinealectomized (Px) while the remaining ones underwent a sham operation (SPx). Two weeks after surgery rats in the 2(nd), 4(th), 6(th) and 8(th) groups were administered MEL (50 microg/100 g of bm) intraperitoneally while the remaining animals were administered solvent only (daily between 5 and 6 pm during a month). The animals were decapitated before the experiment (intact rats), after 2 weeks from Orch and SOrch, Px and SPx, after 4 weeks from MEL or solvent administration and after 4 and 8 weeks from discontinuing administration of MEL, and blood was collected for PICP and ICTP concentrations assays with the use of RIA method. DISCUSSION: In Orch rats, a distinct tendency to increase the studied bone markers, especially ICTP was shown. Pinealectomy had inducing, while MEL suppressing effect upon the level of PICP and ICTP; these changes were more pronounced in Orch + Px and SOrch + Px + MEL groups, respectively. After discontinuing administration of MEL distinct tendency to increase of PICP and ICTP level was shown. CONCLUSIONS: Our findings indicate that MEL is an important modulator of bone tissue metabolism in male rats and that deficiency of MEL concentration may be a co-factor in osteoporosis development.     

Climate-driven impacts of prey abundance on the population structure of a tropical aquatic predator

In the present study we explore how annual variation in climate (late wet-season rainfall) affects population demography in a gape-limited obligate piscivorous predator, the Arafura filesnake Acrochordus arafurae in the Australian tropics. These aquatic snakes display extreme sexual dimorphism, with body sizes and relative head sizes of females much larger than those of males. Two consecutive years with low rainfall during the late wet season reduced the abundance of small but not large sized fish. Although snake residual body mass (RBM, calculated from a general linear regression of ln-transformed mass to ln-SVL) decreased after the first year with low prey availability, it was not until the second year that reduced prey abundance caused a dramatic decline in filesnake survival, and hence in population numbers. Thus, our results suggest that most snakes survived the first year of reduced prey abundance, but a successive year with low prey availability proved fatal for many animals. However, the effects of prey scarcity on RBM and survival fell disproportionately on some size classes of snakes. Medium-sized animals (large males and intermediate-sized females) were affected more dramatically than were small or large snakes. We attribute the higher survival of small snakes to their lower energy needs compared to medium-sized individuals, and the higher survival of large snakes to the continued abundance of large prey (mainly large catfish). Two successive years with low abundance of smaller sized prey thus massively modified the size-structure of the filesnake population, virtually eliminating large males and intermediate-sized females. Our field data provide a clear demonstration of the ways in which stochastic variation in climatic conditions can have dramatic effects on predator population demography, mediated via effects on prey availability.