Inhibitors of ribonucleases

RNases are the most important enzymes of cellular metabolism. They influence gene expression, cell growth and differentiation, participate in cell protection against pathogens and induction of apoptosis. Since intracellular RNases exist mainly in complexes with their inhibitors, the latter are also involved in all above-mentioned processes. The review describes natural protein inhibitors of animal, plant, and bacterial RNases along with synthetic low molecular-weight inhibitors. Special attention is paid to the perspectives of application of RNase inhibitors to therapy of oncological and allergic diseases. Despite wide distribution of RNases and their numerous studies, the number of available natural and synthetic inhibitors of these enzymes remains limited. Creation of highly efficient low-molecular inhibitors of RNase activity of angiogenin and eosinophil-associated RNases, aimed at the therapy of oncological and allergic diseases, still remains quite actual.     

Destabilization and stabilization of poly(A).poly(U) structure by platinum(II) compounds

On the basis of molecular biophysics, a methodology for the analysis of intramolecular structural order of the polynucleotide duplex poly(A).poly(U) has been developed. It was shown that the combination of circular dichroism spectroscopy with differential scanning calorimetry is an optimal approach, which ensures the screening of a wide set of substances and interaction conditions and the choice of compound(s) that can stabilize the structure and increase the biological activity of this duplex. The study is aimed at obtaining a new and highly active antiviral remedy.     

Inhibition of lipase activity by low-molecular-weight chitosan

Inhibition of enzymatic activity of lipase (EC 3.1.1.3) from the fungus Candida rugosa and wheat (Triticum aestivum L.) germ by low-molecular-weight chitosan with an average molecular weight of 5.7 kDa in reactions of p-nitrophenyl palmitate cleavage was studied. Preincubation of lipases with chitosan, prior to addition of the substrate to solution, showed that equilibrium during the lipase-inhibitor complex formation was reached within 30 min. The inhibition constants for C. rugosa lipase and wheat germ lipase were 1.4 and 0.9 mM, respectively. The contribution of electrostatic interactions to the complex formation between chitosan and lipases is insignificant.     

The specific features of coronary artery lesion in patients with signs of high cardiac risk in non-ST segment elevation acute coronary syndrome

The paper covers risk stratification for cardiac events in patients with non-ST segment elevation acute coronary syndrome. It defines an association between risk factors, the specific features of coronary artery lesions, and the outcomes of the disease in relation to the used treatment policy. Particular emphasis is laid on the factors that are a handicap to the detection of a symptom-associated coronary artery in this category of patients.     

Induction of antimicrobial peptide synthesis by fat body cells in Calliphora vicina R.-D. (diptera, calliphoridae) larvae

The fat body is the main place of synthesis if peptide antibiotics in insects. The goal of the present study was the search in the body of the larva Calliphora vicina for humoral factors inducing synthesis of antimicrobial peptides by fat body cells during trauma. The preliminary analysis has shown that the activation factor revealed in hemolymph is the thermostable hydrophilic compound with molecular mass less than 3 kDa. According to results of experiments, the integument epitheliocytes and hemocytes also release the humoral factors directly stimulating synthesis of antimicrobial peptides by fat body.     

Neurogenic and septic inductions of synthesis of peptide antibiotics in larvae of Calliphora vicina R.-D. (Diptera: Calliphoridae)

Synthesis of antimicrobial peptides in diapausing larvae Calliphora vicina can be induced by two different pathways. One pathway is well known in insects and includes recognition of microbial particles by the pattern-recognizing receptors. The other pathway includes perception and transduction of stress signal to immunocompetent cells by neuroendocrine system. This phenomenon consists in stimulation of synthesis of defensins, cecropins, and diptericins under effect of chromic stimulation of mechanoreceptors with ligature applied on the larva head end. Formation of immune response in brain is established to need less than 30 s, after which isolation of the neuroendocrine complex does not eliminate activation of immune response As judging from rate of the neurogenic induction, transduction of the stimulating signal from brain to the immune system cells can be connected with release into hemolymph of biogenic amines or other neurohormones stored preliminarily in the neurohemal organ. The nature of this inductor at present remains unknown, as analysis of role of octopamine, dopamine, and adipokynetic hormone did not reveal stimulating effect on synthesis of bactericidal peptides. Physiological mechanism of this phenomenon is not finally understood, its key links seem to be CNS, hormonal factor of cardial bodies, and system of antimicrobial peptides. Synthesis of antimicrobial peptides is directly regulated by the neuroendocrine system that can produce both stimulating and stress action by reminding in this aspect the known immunoneuroendocrine interrelations in vertebrates. The existence of similar integrating mechanisms in such polar animal kingdom groups which are insects and vertebrates indicate that they are more ancient than this was considered earlier.