Antigenotoxic effect of lipoic acid against mitomycin-C in human lymphocyte cultures

Antitumor agents are used in therapy against many forms of human cancer. One of these is mitomycin-C (MMC). As with many agents, it can interact with biological molecules and can induce genetic hazards in non-tumor cells. One of the possible approaches to protect DNA from this damage is to supply antioxidants that can remove free radicals produced by antitumor agents. Lipoic acid (LA) is known as one of the most powerful antioxidants. The aim of this study was to investigate antigenotoxic effects of LA against MMC induced chromosomal aberrations (CA), sister chromatid exchanges (SCE) and micronucleus (MN) formation in human lymphocytes. Lymphocytes were treated with 0.2 μg MMC/heparinized mL for 48 h. Three different concentrations (0.5, 1, 2 μg/mL) of LA were used together with MMC in three different applications; 1 h pre-treatment, simultaneous treatment and 1 h post-treatment. A negative, a positive and a solvent control were also included. In all the cultures treated with MMC + LA, the frequency of abnormal cells and CA/cell significantly decreased compared to MMC. Statistically significant reduction was also observed in SCE/cell and MN frequencies in all treatments. These results demonstrated anticlastogenic and antimutagenic effects of LA against MMC induced genotoxicity. LA showed the most efficient effect during 1 h pretreatment. On the other hand, MMC + LA treatments induced significant reduction in mitotic index than that of MMC treatment alone. These results are encouraging that LA can be a possible chemopreventive agent in tumorigenesis in both cancer patients and in health care persons handling anti-cancer drugs.     

The effect of crown architecture on dynamic amplification factor of an open-grown sugar maple (Acer saccharum L.)

Tree failure may cause significant economic and societal disruptions in urban environments. A better understanding of the relationship between branches and stem as they affect the dynamic response of decurrent trees under wind loading is needed to reduce the risk of tree failure. Finite element (FE) models were used to identify the parameters that primarily impact tree response. A base model was developed using data from a sugar maple (Acer saccharum L.) located in Belchertown, MA, USA, from which parametric models were subsequently developed. Confidence in the base model was gained by comparing the natural frequency of this tree with experimental results. Results from a parametric study incorporating changes in eight different tree parameters (stem diameter, slenderness ratio of branches, number of branches, damping ratio, branch attachment heights, branch attachment angles, branch azimuth angles, and elastic modulus) are then presented to help identify critical model properties that affect the dynamic amplification factor (Rd) of the tree. A single parameter was varied in each model while keeping others unchanged from the base model. Parameters with the greatest effect on Rd included stem diameter, number and slenderness of branches in the crown, elastic modulus of stem and branches, and damping ratio. Thus, it may be possible to use pruning to alter crown architecture to reduce the risk of tree failure.     

The interdomain interface in bifunctional enzyme protein 3/4A (NS3/4A) regulates protease and helicase activities

Hepatitis C (HCV) protein 3/4A (NS3/4A) is a bifunctional enzyme comprising two separate domains with protease and helicase activities, which are essential for viral propagation. Both domains are stable and have enzymatic activity separately, and the relevance and implications of having protease and helicase together as a single protein remains to be explored. Altered in vitro activities of isolated domains compared with the full‐length NS3/4A protein suggest the existence of interdomain communication. The molecular mechanism and extent of this communication was investigated by probing the domain–domain interface observed in HCV NS3/4A crystal structures. We found in molecular dynamics simulations that the two domains of NS3/4A are dynamically coupled through the interface. Interestingly, mutations designed to disrupt this interface did not hinder the catalytic activities of either domain. In contrast, substrate cleavage and DNA unwinding by these mutants were mostly enhanced compared with the wild‐type protein. Disrupting the interface did not significantly alter RNA unwinding activity; however, the full‐length protein was more efficient in RNA unwinding than the isolated protease domain, suggesting a more direct role in RNA processing independent of the interface. Our findings suggest that HCV NS3/4A adopts an “extended” catalytically active conformation, and interface formation acts as a switch to regulate activity. We propose a unifying model connecting HCV NS3/4A conformational states and protease and helicase function, where interface formation and the dynamic interplay between the two enzymatic domains of HCV NS3/4A potentially modulate the protease and helicase activities in vivo.     

Trace Elements and Heavy Metals in Hair of Stage III Breast Cancer Patients

This prospective study was designed to compare the hair levels of 36 elements in 52 patients with stage III breast cancer to those of an equal number of healthy individuals. Principal component and cluster analysis were used for source of identification and apportionment of heavy metals and trace elements in these two groups. A higher average level of iron was found in samples from patients while controls had higher levels of calcium. Both patients and controls had elevated levels of tin, magnesium, zinc, and sodium. Almost all element values in cancer patients showed higher dispersion and asymmetry than in healthy controls. Between the two groups, there were statistically significant differences in the concentrations of silver, arsenic, gold, boron, barium, beryllium, calcium, cadmium, cerium, cobalt, cesium, gadolinium, manganese, nickel, lead, antimony, scandium, selenium, and zinc (p?相似文献   

Trehalose renders the dauer larva of Caenorhabditis elegans resistant to extreme desiccation

Water is essential for life on Earth. In its absence, however, some organisms can interrupt their life cycle and temporarily enter an ametabolic state, known as anhydrobiosis [1]. It is assumed that sugars (in particular trehalose) are instrumental for survival under anhydrobiotic conditions [2]. However, the role of trehalose remained obscure because the corresponding evidence was purely correlative and based mostly on in vitro studies without any genetic manipulations of trehalose metabolism. In this study, we used C. elegans as a genetic model to investigate molecular mechanisms of anhydrobiosis. We show that the C. elegans dauer larva is a true anhydrobiote: under defined conditions it can survive even after losing 98% of its body water. This ability is correlated with a several fold increase in the amount of trehalose. Mutants unable to synthesize trehalose cannot survive even mild dehydration. Light and electron microscopy indicate that one of the major functions of trehalose is the preservation of membrane organization. Fourier-transform infrared spectroscopy of whole worms suggests that this is achieved by preserving homogeneous and compact packing of lipid acyl chains. By means of infrared spectroscopy, we can now distinguish a "dry, yet alive" larva from a "dry and dead" one.     

Acid proteinase,phospholipase, and biofilm production of <Emphasis Type="Italic">Candida</Emphasis> species isolated from blood cultures

Three virulence factors comprising proteinase, phospholipase, and biofilm among 68 Candida albicans and 31 non-albicans Candida strains (11 C. tropicalis, 8 C. parapsilosis, 6 C. glabrata, 4 C. guillermondii, 2 C. krusei) isolated from blood cultures were analyzed. In total, 61 (89.7%) C. albicans strains were detected as proteinase positive whereas eight (25.8%) non-albicans Candida strains were proteinase positive (P < 0.05). Phospholipase production was detected in 41 (60.3%) C. albicans strains. All non-albicans Candida strains were phospholipase negative. Biofilm production was determined by both visual and spectrophotometric methods. Eight (11.8%) of C. albicans strains and 13 (41.93%) of 31 non-albicans Candida strains were biofilm positive with two of the methods (P < 0.05). According to our results, we may suggest that detection of hydrolytic enzyme and biofilm production abilities of the Candida isolates in clinical mycology laboratories may warn the clinican for a possible hematogenous infection.     

A quantitative colorimetric method of measuring alkaline phosphatase activity in eukaryotic cell membranes

Alkaline phosphatase (ALP) is glycoprotein structured metalophosphatase with several defined functions. It is present in many tissues of all living beings from bacteria to mammals. The enzyme may catalyse the hydrolysis of various monophosphate esters at alkaline pH. The objective of this study was to quantify ALP functioning particularly in the membranes of eukaryotic cells. The membranes of seven different cells (myeloma cells; hybrid cells; erythroleukaemia cells; lymphocytes and erythrocytes) were tested for ALP activity using a cellular enzyme assay, which is based on the conversion of para-nitrophenylphosphate (p-NPP) to para-nitrophenol and the colorimetric determination of the resulting coloured product. The test system was optimised with respect to substrate concentration, reaction time and the number of cells used as a source of enzyme. The obtained values were converted to quantitative results through a standard curve created using commercial ALP. In order to determine the effect of serum concentration on enzyme activity, 1G2 hybridoma, which is among the cells used in this study and which synthesizes monoclonal antibody against human serum albumin, was produced in different serum concentrations ranging from 0 to 15%.     

Loss in moment capacity of tree stems induced by decay

Key message

We model varying decay in tree cross-sections by considering bending theory to estimate moment capacity loss (MCL) for the sections. We compare MCL with experiments on selected oak trees.

Abstract

Tree failures can damage property and injure people, sometimes with fatal consequences. Arborists assess the likelihood of failure by examining many factors, including strength loss in the stem or branch due to decay. Current methods for assessing strength loss due to decay are limited by not accounting for offset areas of decay and assuming that the neutral axis of the cross-section corresponds to the centroidal axis. This paper considers that strength loss of a tree can be related to moment capacity loss (MCL) of the decayed tree cross-section, because tree failures are assumed to occur when induced moments exceed the moment capacity of the tree cross-section. An estimation of MCL is theoretically derived to account for offset areas of decay and for differences in properties of wood under compressive and tensile stresses. Field measurements are used to validate the theoretical approach, and predictions of loss in moment capacity are plotted for a range of scenarios of decayed stems or branches. Results show that the location and size of decay in the cross-section and relative to the direction of sway are important to determine MCL. The effect of wood properties on MCL was most evident for concentric decay and decreased as the location of decay moved to the periphery of the stem. The effect of the ratio of tensile to compressive moduli of elasticity on calculations of MCL was negligible. Practitioners are cautioned against using certain existing methods because the degree to which they over- or underestimate the likelihood of failure depended on the amount and location of decay in the cross-section.     

Health Transformation Project and Defensive Medicine Practice among Neurosurgeons in Turkey

Background

The term “Defensive” medicine was coined in the early 1970′s and has been an important topic of scientific investigation and professional debate ever since.

Objective

The aim of this study was to investigate the characteristics of defensive medicine, its reasons, and the extent to which it is practiced in the Turkish health care system. This is the first national survey to study the practice of defensive medicine among neurosurgeons in Turkey.

Methods

The present cross-sectional study on defensive medicine assessed neurosurgeons registered at the Turkish Neurosurgical Society, who are actively working in various centers and hospitals within the Turkish health care system. A 40-question survey was adapted from existing measures described in the literature and was completed by a total of 404 neurosurgeons, representing 36.7% of the neurosurgeons registered at the Turkish Neurosurgical Society.

Results

Seventy-two percent of the participants in the current study reported practicing defensive medicine. This practice was mainly reported among inexperienced neurosurgeons (74.4%). Most were younger than 40 years of age (75.2%), working in state hospitals/universities (72.7%), and living in the Marmara region (38%). Respondents reported engaging in defensive medicine by avoiding high-risk surgery (62.6%), ordering additional imaging studies (60.9%) and laboratory tests (33.7%), and referring patients to consultants (31.2%). Most participants consider every patient as a potential threat in terms of a medical lawsuit (68.3%) and do not believe the courts can distinguish malpractice from complications (89.6%).

Conclusion

Concerns and perceptions about medical liability lead neurosurgeons to practice defensive medicine. By avoiding high-risk surgery, ordering unnecessary diagnostic tests, and referring the patients to consultants, neurosurgeons try to minimize the risk of malpractice and protect themselves from legal risks, resulting in higher healthcare expenditure and longer treatment periods.