Carabid beetle diversity and mean individual biomass in beech forests of various ages

Carabid beetle diversity and mean individual biomass (MIB) were analysed in three different successional stages of beech tree stands (60, 80 and 150 years old). Carabid beetles were captured using pitfall traps placed at nine sites (three per age class) in the Papuk Mountain of East Croatia during 2008. A cluster analysis identified three groupings that corresponded to the beech age classes. MIB values increased with stand age, ranging from 255 in 60-year-old stand to 537 in the oldest forests. The 80-year-old stand showed the highest species richness and diversity values. With respect to species composition, large species such as Carabus scheidleri and Carabus coriaceus were dominant only in the oldest forests. Furthermore, species that overwinter in the larval stage were more abundant in the oldest forests (45% of the total number of individuals from the 150-year-old stand) than in the younger ones (20% of individuals from 60-year-old, and 22% of individuals from 80-year-old stands). Our results showed that the analyses of species composition and life history traits are valuable for estimating the conservation values of older forests. Although the investigated sites form part of a continuous forested area and are only a couple of kilometres apart, MIB values detect significant differences associated with forest age and can be a useful tool in evaluating the degree to which a forest reflects a natural state.     

Suicide index reduction in Slovenia: the impact of primary care provision

Background Education of primary care providers about diagnosis and treatment of depression and anxiety is an evidence-based suicide prevention measure.Aim To analyse suicide index, mental health epidemiological data and primary care provision in Slovenian regions and to identify examples of good suicide prevention practices in different Slovenian regions.Methods Analysis of existent epidemiological data on mental health in Slovenia.Results Anxiety and depression are the most common complaints in a representative sample of the Slovene population. The number of suicides in Slovenia had been dropping in the period from 2002 to 2006 and was again slowly rising in 2008. The number of visits to family physicians' practices because of mental health problems is low in comparison to other European countries, which might be attributed also to the high workload of family physicians. Suicide prevention programmes follow the example of the Suicide Prevention Project in the central-east region of Slovenia. This programme is based on education of primary care providers and the general public about recognition and treatment of depression in line with international guidelines.Conclusions The differentiation of causes for suicide reduction needs further research, as well as urgent improvement in the accessibility of primary care teams in Slovenia.     

Virtual screening for potential inhibitors of bacterial MurC and MurD ligases

Mur ligases are bacterial enzymes involved in the cytoplasmic steps of peptidoglycan biosynthesis and are viable targets for antibacterial drug discovery. We have performed virtual screening for potential ATP-competitive inhibitors targeting MurC and MurD ligases, using a protocol of consecutive hierarchical filters. Selected compounds were evaluated for inhibition of MurC and MurD ligases, and weak inhibitors possessing dual inhibitory activity have been identified. These compounds represent new scaffolds for further optimisation towards multiple Mur ligase inhibitors with improved inhibitory potency.     

Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

ABSTRACT: BACKGROUND: Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive.The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. METHODS: Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded. DISCUSSION: This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management.This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).     

In vitro bioactivation of bazedoxifene and 2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol in human liver microsomes

Bazedoxifene is a selective estrogen receptor modulator (SERM) that has been developed for use in post-menopausal osteoporosis. However, it contains a potentially toxic 5-hydroxy-3-methylindole moiety. Previous studies on the 5-hydroxyindole and the 3-alkylindole-containing drugs indometacine, zafirlukast and MK-0524 structural analogs have shown that they are bioactivated by cytochrome P450s through a dehydrogenation process to form quinoneimine or 3-methyleneindolenine electrophilic species. In the present study, bazedoxifene was synthesized and then evaluated, together with raloxifene and 2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol (13), a 3-methyl-5-hydroxyindole-based structural fragment of bazedoxifene, for its ability to form reactive electrophilic species when incubated with human liver microsomes (HLMs) or recombinant CYP isozymes. We showed that bazedoxifene was bioactivated only in trace amounts with recombinant CYP isozymes. In contrast, the N-dealkylated fragment of bazedoxifene (2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol) was bioactivated in considerable amounts to an electrophilic intermediate, which was trapped with glutathione and identified by LC-MS/MS. This suggests that bazedoxifene would require initial N-dealkylation, which could subsequently lead to the formation of the reactive intermediate. However, such an N-dealkylated metabolite of bazedoxifene was not detected after the incubation of bazedoxifene in HLM or recombinant CYP isozymes.     

Novel thrombin inhibitors incorporating weakly basic heterobicyclic P1-arginine mimetics: optimization via modification of P1 and P3 moieties

Optimization of lead compounds 1 and 2 resulted in novel, selective, and potent thrombin inhibitors incorporating weakly basic heterobicyclic P(1)-arginine mimetics. The design, synthesis, and biological activity of racemic thrombin inhibitors 17-29 and enantiomerically pure thrombin inhibitors 30-33 are described. The arginine side-chain mimetics used in this study are 4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine, 4,5,6,7-tetrahydro-2H-indazole, and 2-imino-4,5,6,7-tetrahydro-1,3-benzothiazol-3(2H)-ylamine.     

High nitrate removal from synthetic wastewater with the mixed bacterial culture

The applicability of the mixed bacterial culture, originated from two-stage anaerobic-aerobic industrial yeasts production wastewater treatment plant for high rate denitrification processes was investigated. After acclimation to nitrate, the dominant strains were Pseudomonas and Paracoccus sp. Complete denitrification with low accumulation of nitrite-N (0.1 mg/l) was found in synthetic wastewater, obeying a zero-order reaction with respect to nitrate and a first-order reaction with respect to biomass concentration. Denitrification was then monitored in the continuous-flow stirred reactor at different hydraulic retention time, HRT (62-28 h) in order to achieve the optimal HRT. Nitrate was completely removed during following 45 days, at 25 degrees C with HRT, which we reduced from 62 to 28 h. Yet still, at 28 h HRT, high average specific denitrification rate of 142 mg NO3- -N/g VSS h was obtained.     

Membrane-active antimicrobial peptide identified in Rana arvalis by targeted DNA sequencing

Antimicrobial peptides (AMPs) are naturally produced, gene encoded molecules with a direct antimicrobial activity against pathogens, often also showing other immune-related properties. Anuran skin secretions are rich in bioactive peptides, including AMPs, and we have reported a novel targeted sequencing approach to identify novel AMPs simultaneously in different frog species, from small quantities of skin tissue. Over a hundred full-length peptides were identified from specimens belonging to five different Ranidae frog species, out of which 29 were novel sequences. Six of these were selected for synthesis and testing against a panel of Gram-negative and Gram-positive bacteria. One peptide, identified in Rana arvalis, proved to be a potent and broad-spectrum antimicrobial, active against ATCC bacterial strains and a multi-drug resistant clinical isolate. CD spectroscopy suggests it has a helical conformation, while surface plasmon resonance (SPR) that it may self-aggregate/oligomerize at the membrane surface. It was found to disrupt the bacterial membrane at sub-MIC, MIC and above-MIC concentrations, as observed by flow cytometry and/or visualized by atomic force microscopy (AFM). Only a limited toxicity was observed towards peripheral blood mononuclear cells (PBMC) with a more pronounced effect observed against the MEC-1 cell line.     

Lenticulostriatal vasculopathy - a marker for congenital cytomegalovirus infection?

Lenticulostriate vasculopathy (LSV) is an ultrasound (US) visible lesion of the brain, which appears as echogenic streaks or spots in the arteries of thalamus and basal ganglia. LSV has varied etiology. Transfontanelar Color Doppler (TFCD) can easily display lenticulostriatal blood flow and assess: stage I LSV with present flow within echogenic changes and stage II LSV in which the flow disappears, despite a presence of streaks and spots, which at this stage most probably correspond to calcification. The objectives of this study are to determine: (1) Whether there are differences in distribution (unilateral or bilateral) and presence (during first year of age) of TFCD flow between congenital CMV infection positive and negative group of children with LSV (2) Could US and TFCD findings of LSV be an indication for further investigation of possible congenital CMV infection, because of their variable and often adverse neurodevelopmental outcome? We examined and followed-up 98 infants with LSV One group (37/98) with congenital CMV infection and second (61/98) negative. All infants had clinical signs of neuromotor delay and ultrasound and TFCD markers of LSV Our study shows that most of the patients from both groups had TFCD visible flow at the age of 0-4 months. In majority of them in both groups, at the age of 5-8 months, there was no more visible flow. TFCD showed no statistically significant difference among congenital CMV infection positive group and negative group, nor in youngest age period (0-4 months), nor in later course of flow in LSV unilaterally or bilaterally. Although the LSV presents nonspecific marker for intracranial infection (ICI), all infants presenting with LSV should be evaluated for possible ICI. Thus, the Doppler findings of LSV in infants require a detailed examination, monitoring and follow-up of neuromotor outcome.     

Malformations of cortical development in children with congenital cytomegalovirus infection - A study of nine children with proven congenital cytomegalovirus infection

Congenital cytomegalovirus (CMV) infection is the most common vertically transmitted disease with the rate of the infection ranging from 0.2 to 2.4% in newborn infants. Congenital CMV infection causes multiorgan affection, but the most severe and permanent sequelae are those affecting central nervous system such as mental retardation, cerebral palsy, sensorineural hearing loss, chorioretinitis and seizures as a result of direct interference of the virus with neurogenesis. The time of acquiring infection is strongly connected to the level of child's disability. Infection in early pregnancy results in severe neurological sequelae, while later infection has less prominent signs. Radiological findings show connection between onset of infection and brain imaging, from lissencephaly, pachygyria, polymicrogyria, schizencephaly, calcification, cerebellar hypoplasia and/or hypoplasia/agenesis of corpus callosum as a result of an early infection, to white matter abnormalities including disturbed myelination as a result of a late infection. We present nine patients with proven congenital CMV infection and malformations of cortical development and their computed tomography/magnetic resonance (CT/MRI) findings along with clinical assessments. According to CT/MRI results we assume that two of our children with lissencephaly had an early onset of infection. The other seven with less severe cortical dysplasia in form of pachy/polymicrogyria were probably infected later Cerebellar hypoplasia and/or calcifications in our patients also confirm an early onset of infection. Developmental outcome in all of our children was poor: moderate to severe psychomotor retardation has been diagnosed in all children; five of them have developed cerebral palsy (four have bilateral spastic and one dyskinetic) and one is estimated to have minor motor dysfunction. Seven out of nine developed epilepsy, chorioretinitis was found in three of them and sensorineural deafness in two of them. All of our children, except one, were presented by symptomatic infection, yet only four of them were recognized at birth. Therefore, congenital CMV infection should be considered as one of the reasons for childhood disability more often.