Chemical Composition of Volatiles of Eight Geranium L. Species from Vlasina Plateau (South Eastern Serbia)

Geranium species are widely used in traditional medicine of Balkan. The aim of this work was to investigate and compare chemical composition of volatile fractions obtained by hydrodistillation from aerial parts of G. macrorrhizum, G. phaeum, G. sanguineum, G. robertianum, G. palustre, G. pyrenaicum, G. columbinum and G. lucidum as well as from underground parts of G. macrorrhizum and G. phaeum, originated from Vlasina plateau in South Eastern Serbia. The volatiles were analyzed using GC/MS and GC‐FID. G. palustre volatiles have been studied for the first time with β‐selinene (18.6 %) as a characteristic compound. The cluster analysis revealed separation of volatiles into two main groups. Volatile fractions of G. macrorrhizum were separated from all other samples due to high sesquiterpene content (92.3 % in aerial and 94.6 % in underground parts). The volatile fractions of other samples were mainly composed of sesquiterpenes (10.8–61.8 %), diterpenes (12.9–43.0 %) and fatty acids and their derivatives (6.6–21.6 %) with the exception of volatile fraction of G. phaeum underground parts which was dominated only by fatty acids and their derivatives (76.6 %). The results presented in this article contribute to the knowledge on the chemistry of this genus and advances the knowledge on flora of southeast Serbia.     

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).     

Effects of loading on maximum vertical jumps: Selective effects of weight and inertia

A novel loading method was applied to explore selective effects of externally added weight (W), weight and inertia (W+I), and inertia (I) on maximum counter-movement jumps (CMJ) performed with arm swing. Externally applied extended rubber bands and/or loaded vest added W, W+I, and I corresponding to 10-40% of subjects' body mass. As expected, an increase in magnitude of all types of load was associated with an increase in ground reaction forces (GRF), as well as with a decrease in both the jumping performance and power output. However, of more importance could be that discernible differences among the effects of W, W+I, and I were recorded despite a relatively narrow loading range. In particular, an increase in W was associated with the minimal changes in movement kinematic pattern and smallest reduction of jumping performance, while also allowing for the highest power output. Conversely, W+I was associated with the highest ground reaction forces. Finally, the lowest maxima of GRF and power were associated with I. Although further research is apparently needed, the obtained finding could be of potential importance not only for understanding fundamental properties of the neuromuscular system, but also for optimization of loading in standard athletic training and rehabilitation procedures.     

Insulin-like growth factor I prevents corticosteroid-induced diaphragm muscle atrophy in emphysematous hamsters

The aim of this study was to evaluate whether recombinant human insulin-like growth factor I (rhIGF-I) could attenuate or prevent diaphragm (DIA) fiber atrophy with corticosteroid (CS) administration to emphysematous (EMP) hamsters. DIA muscle IGF-I responses to CS administration with and without exogenous rhIGF-I administration were evaluated. Three groups were studied: 1) EMP; 2) EMP + triamcinolone (T; 0.4 mg.kg-1.day-1 im); and 3) EMP + T + IGF-I (600 microg/day by constant infusion). After 4 wk, the DIA was analyzed histochemically and biochemically (IGF-I mRNA levels by RT-PCR and endogenous and exogenous IGF-I peptide levels immunochemically). Body weights of EMP-T progressively decreased, while those of EMP and EMP-T-IGF-I remained stable despite similarly reduced food intake in both T groups. DIA weight was reduced with T but preserved with rhIGF-I infusion. DIA fiber proportions were similar among the groups. The cross-sectional areas of types I, IIa, and IIx fibers were reduced (17 to 31%) with T administration but unchanged with rhIGF-I infusion. DIA IGF-I mRNA levels were similar across all groups. By contrast, the endogenous DIA IGF-I levels were reduced (41%) in the EMP-T-IGF-I animals. Total DIA IGF-I levels (endogenous + exogenous) were still significantly reduced. IGF-I immunoreactivity confirmed this reduction in all DIA fibers. We conclude that DIA fiber atrophy with T was completely prevented by exogenous rhIGF-I administration. This effect was likely mediated by the pharmacological influences of exogenously administered rhIGF-I. We speculate that this results from increased bioavailability of free IGF-I to react with muscle receptors. Reduced endogenous IGF-I levels in the DIA likely reflect a negative-feedback influence. These results may have important clinical implications for treatment options to offset the adverse effects of CS on the respiratory muscles in patients with chronic lung disorders.     

Immunization using an Apo B-100 related epitope reduces atherosclerosis and plaque inflammation in hypercholesterolemic apo E (-/-) mice

Immune system modulates atherosclerosis and immunization using homologous LDL reduces atherosclerosis in hyperlipidemic animals. The nature of athero-protective antigenic epitopes in LDL remains unclear. We have recently identified nearly a 100 antigenic epitopes in human apo B-100 and in this study we evaluated the effects of immunization with two such epitopes on atherosclerosis in hypercholesterolemic apo E (-/-) mice. Male apo E (-/-) mice were immunized at 6-7 weeks of age with two different apo B-100 related peptide sequences using alum as adjuvant and mice immunized with alum alone served as controls. Peptide-2 immunization reduced aortic atherosclerosis by 40% and plaque inflammation by 80% compared to controls without a reduction in circulating cholesterol levels whereas Peptide-1 immunization had no effect. Peptide-2 immunization also reduced the progression of aortic lesions when mice were immunized at 16 weeks of age, suggesting the possibility of immuno-modulation in treating established atherosclerosis. The athero-protective effect of Peptide-2 immunization was absent in splenectomized mice but could be conveyed to non-immunized mice via adoptive transfer of splenocytes from peptide-2 immunized mice. In conclusion, immunization with a specific apo B-100 related peptide sequence reduces aortic atherosclerosis and plaque inflammation. Such acquired immunity and athero-protective effect appears to be mediated by splenocytes. These data demonstrate the feasibility of peptide based immunomodulating therapy for atherosclerosis.     

The role of microcystins in heavy cyanobacterial bloom formation

The presence of high microcystin concentrations in cyanobacterialblooms additionally affects species diversity. Blooms with hightoxin contents can reach higher cell densities, which is alsodemonstrated by microcystin cell contents. In vitro experimentsshow that microcystins influence phytoplankton proliferation.The action is strongly dependent on the phytoplankton speciestested and light conditions. We propose that the environmentalimpact of different microcystins depends on their enzymaticinhibition activity and thus could not be measured merely onthe basis of their toxicity to vertebrate species. Their rolein heavy cyanobacterial bloom and scum formation is discussed,as well as their impact on the massive proliferation of otherspecies following toxic cyanobacterial bloom degradation.     

A code within a code: how codons influence mRNA stability

The genetic code was deciphered more than 50 years ago, but we are only now becoming aware of a second, hidden code. It is the concept of “codon optimality” that enters the scene of developmental and homeostatic gene expression, linking translation rates, mRNA stability, and tRNA abundance. Both at the biological and methodological levels, work by Giraldez and colleagues in this issue of The EMBO Journal paves the way for further analyses of such key regulatory mechanisms.     

Mechanism and thermodynamics of binding of the polypyrimidine tract binding protein to RNA

The polypyrimidine tract binding protein (PTB) is involved in many physiological processes, including alternative splicing, internal ribosomal entry side (IRES)-mediated initiation of translation, and polyadenylation, as well as in ensuring mRNA stability. However, the role of PTB in these processes is not fully understood, and this has motivated us to undertake a computational study of the protein. PTB RNA binding domains (RBDs) 3 and 4 and their complexes with oligopyrimidine RNAs were simulated using the GROMOS simulation software using the GROMOS 45A4 force field. First, the stability and fluctuations of the tertiary fold and of the secondary structural elements in individual domains, the combined RBD34 domain, and their complexes with RNA were studied. Second, the simulation results were validated against the experimental NMR NOE data. The analysis of hydrogen bonding patterns, salt bridge networks, and stacking interactions of the RNA to the binding pockets of the protein domains showed that binding is not sequence-specific and that many RNA fragments can bind to them successfully. Further calculations of the relative free energy of binding for different polypyrimidine sequences were carried out using the thermodynamic integration (TI) and single-step perturbation (SSP) methods. It is was not possible to calculate the relative free energies with high accuracy, but the obtained results do give qualitative insights into PTB's affinity for different RNA sequences. Furthermore, the low-energy conformations of the complexes that were found provided additional information about the mechanism of binding.     

The pore-forming action of polyenes: From model membranes to living organisms

The incidence of resistant fungal pathogens has been increasing, especially in immuno-compromised people. As such, considerable research has been focused on discovering anti-fungal agents with new mechanisms of action and on optimizing the use of existing agents. In this context, interest in the polyene group of anti-fungals has recently been renewed, since they are known to be effective against a broad spectrum of fungal pathogens that only rarely develop a resistance to them. In the past 10?years considerable efforts have been made to improve their efficacy and, simultaneously, to reduce their toxicity. Knowledge about the basic mechanisms of their action will be of crucial importance to further optimizing their use. The mechanisms of polyene action at the membrane level are reviewed here, focusing primarily on their pore-forming activity and on the resulting osmotic responses of artificial lipid vesicles and different eukaryotic cells.