New trends in platinum and palladium complexes as antineoplastic agents

The discovery of cisplatin (cis-Pt(NH3)2Cl2) as an antineoplastic agent has focused attention on the rational design of metal complexes that can be potentially used in cancer chemotherapy. Today, the pharmaceutical industry invests more than $1 billion each year in the development of new metal-based drugs to improve biological activities, in terms of cellular selectivity, therapeutic efficiency and minimization of side effects. Chemotherapies based on transition metals play a key role in cancer treatment, and among them platinum and palladium are the most fruitful. This article reviews the main recent advances in the design and synthesis of platinum- and palladium-based drugs, their structural features and biological studies of them. The rationale for the choice of the ligand, related to leaving groups, the geometry of the complex and the oxidation state of the metal ion, is discussed. An overview of the main biological techniques and approaches for testing the interaction of these molecules with the biological environment, mainly DNA, to validate the effect is also provided

Natural zeolites chabazite/phillipsite/analcime increase blood levels of antioxidant enzymes

Imbalance between reactive oxygen species generation and antioxidant capacity induces a condition known as oxidative stress which is implicated in numerous pathological processes. In this study we evaluated whether natural zeolites chabazite/phillipsite/analcime may affect the levels of different antioxidant enzymes (gluthatione peroxidase, superoxide dismutase, gluthatione reductase), total antioxidant status and oxidative stress in 25 clinically healthy men, both non-smokers and smokers. Measurements were performed on whole blood or on plasma samples before (T0) and after 4-weeks zeolites intake (T1). At T1, gluthatione peroxidase, superoxide dismutase and gluthatione reductase increased compared to T0 levels, both considering all subjects as joint and after subdivision in non-smokers and smokers. Differently, a reduction in total antioxidant status was observed at T1. Anyway, total antioxidant status resulted higher than the reference values in both groups at each time point. A decrease in lipid peroxidation, a major indicator of oxidative stress assessed by monitoring thiobarbituric acid reactive substances, was also observed in all subjects at T1. Our results suggested that chabazite/phillipsite/analcime may help to counteract oxidative stress in apparently healthy subjects exposed to different oxidative stress risk factors, such as smoking, thus representing a particular kind of food with potential antioxidant properties

Altered expression of antioxidant enzymes and autophagic proteins in transglutaminase 2 knockout mice

""Background. Transglutaminases (TGs) are ubiquitous calcium-dependent acyl-transferases, catalysing post-translational protein modifications. Among the family members, TG2 (or "tissue" transglutaminase) acts as a multifunctional protein regulating cell processes, including autophagy [1,2]. . TG2 is highly expressed in the nervous tissue and reportedly involved in neurodegenerative disorders [3]. Indeed, the pathophysiology of these diseases includes insoluble aggregate formation, and covalent cross-linking of pathogenic proteins by TG2 has been suggested. Another hallmark of neurodegeneration is dysregulated autophagy, thus making the role played by TG2 in this cellular process especially relevant. Interestingly, conditions promoting TG2 activity, such as low GTP and high calcium levels, associated with oxidative stress, occur in neurodegeneration. . The present study aims to clarify the role of TG2 in redox balance and autophagy. To this purpose, the expression levels of antioxidant enzymes and pro-autophagic proteins were investigated in various brain regions and liver of TG2-\\\/- mice. . . Materials and methods. Expression of antioxidant enzymes, namely superoxide dismutase 1 and 2 (SOD1, SOD2), catalase (CAT) and glutathione peroxidase 1 (GPX1), and autophagic proteins (Beclin1, LC3 and AMBRA1) were evaluated by Western blotting (WB) and immunohistochemistry in selected brain areas (neocortex, hippocampus, brainstem, and cerebellum) and liver of 12-month-old TG2-\\\/- and wild-type mice.. . Results. WB and immunohistochemical data reveal altered expression patterns of antioxidant enzymes in both liver and brain tissues. Of particular interest is the statistically significant decrease of CAT and SOD2 in the cerebellum and hippocampus of TG2-\\\/- mice, while unchanged levels of these proteins are detected in the neocortex and brainstem. In the knockout liver, even more dramatic reduction of CAT and SOD2 expression is found, while SOD1 is intriguingly upregulated. Concerning the effect of TG2 deletion on autophagy, Beclin1 is down-regulated in the neocortex and hippocampus of knockout mice.. . Conclusions. Overall, our data on TG2-\\\/- mice support the involvement of the transamidating enzyme in controlling redox balance of different organs, and in regulating autophagic flux [1-3]. The specific decrease in the peroxisomal enzyme CAT and in the mitochondrial protein SOD2 emphasizes the role of these organelles in oxidative stress management and their interplay in cell metabolism. Moreover, region-based differences in the effect of TG2 deletion may reflect multiple functions related to the organ, tissue and cell type.. "

Estimating abundance and habitat suitability in a micro-endemic snake: the Walser viper

Recently described species suffer lack of information that hampers setting up appropriate conservation strategies. The situation is particularly complex with micro-endemic snakes, for which detection and monitoring are particularly challenging. The Walser viper Vipera walser is a recently described snake inhabiting a small area of the SW Italian alps. We combined information on species distribution with repeated monitoring to identify the areas most suitable for the species, and to obtain estimates of species abundance. Species distribution models were used to identify the topographical, climatic, and land-cover features related to the occurrence of vipers. Furthermore, repeated transects and N-mixture models were used to estimate abundance and to identify factors related to the variation of abundance. The available data suggested that the species has a disjunct range, with a Northern range of ~45 km2 , and a southern range of ~225 km2. Distribution models suggested that vipers are associated with areas with open egetation,altitude between 1300 and 2300 m, high precipitation, low forest cover, low slope, and southern aspect. N-mixture models confirmed very low detection probability of these vipers, and suggested that the species has a low abundance,with the highest abundance in south-facing plots. We provide the first quantitative information on habitats and abundance variation for Walser vipers. The broad confidence intervals of abundance estimates exemplify the complexity of providing range-wide measures of abundance for secretive species. Given the narrow range of these vipers, continuous monitoring is required to understand how they respond to ongoing environmental changes in mountainous areas

A mouse mammary tumor virus env-like exogenous sequence is strictly related to progression of human sporadic breast carcinoma

A viral etiology of human breast cancer (HBC) has been postulated for decades since the identification of mouse mammary tumor virus (MMTV). The detection of MMTV env-like exogenous sequences (MMTVels) in 30% to 40% of invasive HBCs increased attention to this hypothesis. Looking for MMTVels during cancer progression may contribute to a better understanding of their role in HBC. Herein, we analyzed HBC preinvasive lesions for the presence of MMTVels. Samples were obtained by laser microdissection of FFPE tissues: 20 usual-type ductal hyperplasias, 22 atypical ductal hyperplasias (ADHs), 49 ductal carcinomas in situ (DCISs), 20 infiltrating ductal carcinomas (IDCs), and 26 normal epithelial cells collateral to a DCIS or an IDC. Controls included reductive mammoplastic tissue, thyroid and colon carcinoma, and blood samples from healthy donors. MMTVels were detected by fluorescence-nested PCR. DNA samples from the tissues of nine patients were analyzed by real-time quantitative PCR, revealing a different viral load correlated with stage of progression. Furthermore, as never previously described, the presence of MMTVels was investigated by chromogenic in situ hybridization. MMTVels were found in 19% of normal epithelial cells collateral to a DCIS or an IDC, 27% of ADHs, 82% of DCISs, and 35% of IDCs. No MMTVels were found in the control samples. Quantitative PCR and chromogenic in situ hybridization confirmed these results. These data could contribute to our understanding of the role of MMTVels in HBC. (Am J Pathol 2011, 179:2083-2090; DOI: 10.1016/j.ajpath.2011.06.046

When does cyclic dominance lead to stable spiral waves?

Species diversity in ecosystems is often accompanied by characteristic spatio-temporal patterns. Here, we consider a generic two-dimensional population model and study the spiraling patterns arising from the combined effects of cyclic dominance of three species, mutation, pair-exchange and individual hopping. The dynamics is characterized by nonlinear mobility and a Hopf bifurcation around which the system's four-phase state diagram is inferred from a complex Ginzburg-Landau equation derived using a perturbative multiscale expansion. While the dynamics is generally characterized by spiraling patterns, we show that spiral waves are stable in only one of the four phases. Furthermore, we characterize a phase where nonlinearity leads to the annihilation of spirals and to the spatially uniform dominance of each species in turn. Away from the Hopf bifurcation, when the coexistence fixed point is unstable, the spiraling patterns are also affected by the nonlinear diffusion