Antioxidant effect of humic acids on rat hepatocytes

The antioxidant properties of humic acids of various origins have been investigated (from bio-humus, black soil from Ternopil region, and peat from different regions, such as: Velykyi Liubin, Drohobych and Belarus Republic). Titrimetric analysis has been shown the quantitative composition of the acidic functional groups of the obtained humic acids. According to the data of thermogravimetric analysis, the values of parameters, showing the ratio of their aliphatic to the cyclic part were determined. It was found that all obtained humic acids are characterized by high antioxidant activity: the formation of thiobarbituractive products and carbonyl groups of proteins in liver hepatocytes were decreased. The inhibition of the products of free radical formation of lipid components and proteins was better inhibited by 1% solutions of humates from vermicompost and humic acids from peat. The results indicate prospects of the humic acids for creating the means of restoring the physiological functions of biological objects in pathological conditions under conditions of free radical stress for application in cosmetic pharmaceutical products.

Synthesis, properties and crystal structure of novel Copper(II) ammine complex with [Pd(CN)4]2− building blocks

The title compound [Cu4(NH3)12-(µ2-CN)8-Pd4(CN)8] was prepared from the aqueous solution Cu2+ – N,N,N′,N′-tetraethylethane-1,2-diamine – [Pd(CN)4]2−, where the addition of excess amounts of ammonia caused the dissolution of the precipitate formed during reaction. Using this method, we prepared and structurally characterized the new complex of Cu(II) containing ammine ligand with tetracyanidopalladate(II) anion incorporated within the molecule. The crystal structure of compound is molecular; the unit cell contains centrosymmetric octanuclear molecules in which all central atoms lies on mirror plane. Generally, the structure of the molecule can be divided into central cyclic part and terminal pendants. The structure contains nitrogen atoms derived from the ammonia molecules coordinated to Copper(II) atoms. They are involved in the formation of N-H···N hydrogen bonds type.

Mild and efficient 64Cu labeling of perhydro-1, 4-diazepine derivatives for potential use with large peptides, proteins and antibodies

DATA (6-Amino-1,4-diazapine-triacetate) and AAZTA (6-Amino-1,4-diazapine-tetracetate) chelators represent a novel approach representing hybrid-chelates: possessing significant cyclic and acyclic character. It is believed that flexibility of the acyclic part facilitates rapid complexation, whilst the preorganized cyclic part minimizes the energy barrier to complexation and inhibits decomplexation processes. So far, these chelators have been used exclusively with 44Sc and 68Ga only. Recent results with natCu predict high stabilities for Cu-AAZTA, yet no radioactive labeling of AAZTA or DATA with 64Cu or any additional radioactive isotope has been reported. We present the one pot synthesis of the bifunctional derivatives AAZTA5OMe and DATA5mOMe and their labeling with 64Cu. In addition, in vitro stability of the respective complexes are presented.

Cycles and Intractability in a Large Class of Aggregation Rules

We introduce the (j,k)-Kemeny rule -- a generalization of Kemeny's voting rule that aggregates j-chotomous weak orders into a k-chotomous weak order. Special cases of (j,k)-Kemeny include approval voting, the mean rule and Borda mean rule, as well as the Borda count and plurality voting. Why, then, is the winner problem computationally tractable for each of these other rules, but intractable for Kemeny? We show that intractability of winner determination for the (j,k)-Kemeny rule first appears at the j=3, k=3 level. The proof rests on a reduction of max cut to a related problem on weighted tournaments, and reveals that computational complexity arises from the cyclic part in the fundamental decomposition of a weighted tournament into cyclic and cocyclic components. Thus the existence of majority cycles -- the engine driving both Arrow's impossibility theorem and the Gibbard-Satterthwaite theorem -- also serves as a source of computational complexity in social choice.

Comparison of Cyclic and Burst Test Result With FE Simulation of a Locally Thinned Pipe Bend

Thinning of Carbon steel pipe subjected to water flow has been observed in many piping systems. The feeder pipes in CANDU® reactors have been found susceptible to this degradation mechanism. In response, an industry program has been initiated to investigate the effect of local thinning on structural integrity. A CANDU® feeder pipe bend specimen was thinned locally to about 70% of pressure based thickness near the weld at the onset of the bend. The test specimen was subjected to severe pressurized cyclic bending for over 1600 cycles, and was subsequently pressurized to failure under a constant applied bending deformation. The failed specimen was subjected to metallurgical examination. The present paper reports the results of a finite element analysis of the cyclic part of the test and an elastic plastic analysis for failure under pressurization. The results are compared with the experimental outcomes. The conclusions address specifically the test, more generally the failure of thinned pipe and the use of elastic-plastic finite element analysis to predict failure due to pressurization.

A New Type of Modified Brassinosteroids for Enzyme-linked Immunosorbent Assay

New modified brassinosteroids (BS) with a full set of specific functional groups and with an additional one at C-26 have been synthesized and used as haptens for enzyme-linked immunosorbent assay. The haptens were conjugated to bovine serum albumin (BSA) and the obtained immunoconjugates were applied for production of polyclonal antibodies. A conjugation of the haptens to horseradish peroxidase (HRP) gave the corresponding enzyme-labeled BS – another principal component for immuno-competitive analysis. The steroids were linked to proteins through spacers at the terminal side chain carbon atom (C-26) that made both the cyclic part and the side chain exposed for recognition by antibodies. It allowed maximization of their sensitivity and for the first time made possible immunochemical distinguishing of the most important group of natural BS, B-lactones, from B-ketones and 6-deoxo derivatives. The synthesis of haptens based on a sequence of transformations starting from stigmasterol included Claisen rearrangement of 22-allylic ethers as a key reaction in the side chain construction.

Neopeptide Antibiotics That Function as Opsonins and Membrane-Permeabilizing Agents for Gram-Negative Bacteria

ABSTRACT We suggest a novel approach to enhancing antimicrobial drug action by utilizing engineered peptide conjugates. Our most potent conjugates, [fMLF]PMBN and [fMLF]PMEN, are nonapeptides derived from polymyxin B's (PMB's) cyclic moiety (Thr-Dab-cyclo[Dab-Dab-d-Phe-Leu-Dab-Dab-Thr], where Dab is 2,4-diaminobutyric acid) and polymyxin E's (PME's) cyclic moiety (Thr-Dab-cyclo[Dab-Dab-d-Leu-Leu-Dab-Dab-Thr]), respectively, attached to a linear tail comprised of formyl-Met-Leu-Phe (fMLF). The cyclic part binds to gram-negative lipopolysaccharides, rendering the bacterial outer membrane permeable to hydrophobic antibiotics. The tail confers chemotactic and opsonic activities upon the conjugates. These two activities appear to be the basis for the conjugates' antibacterial activities. The conjugates are 8 to 10 times less toxic than the parent PMB or PME antibiotics. Fourteen of 18 mice lethally challenged with erythromycin-resistant Klebsiella pneumoniae survived following intraperitoneal administration of erythromycin and [fMLF]PMBN, whereas erythromycin or the peptide conjugate alone had no effect. Moreover, the clearance of Klebsiella from blood was markedly enhanced by intravenous injection of the [fMLF]PMEN peptide conjugate compared to the clearance of the organism from the mice treated with buffer alone as a control and was similar to that achieved by the PME antibiotic. Blood clearance was also significantly enhanced by administration of PMEN either alone or in a mixture with fMLF, although the effect was less than that produced by the peptide conjugate. Since resistance to polymyxins, the parent molecules of the synthetic cyclic peptides, is rare, the emergence of bacteria resistant to the antimicrobial properties of the peptide conjugates may be precluded as well.

Raman Optical Activity of the Central Part of Hinge Peptide

Central cyclic part of the hinge peptide (a parallel dimer of the pentapeptide Boc-Cys-Pro-Pro-Cys-Pro-NHCH3 with two disulfide bonds) derived from the sequence of human IgG1 is a rather rigid structure having predominantly polyproline II helical conformation as shown by vibrational circular dichroism spectra. It exhibits significant Raman optical activity (ROA) signal due to vibrations associated with the disulfide bridges. We report positive ROA for the S-S stretching vibration at 510 cm-1 and for the C-S stretching vibration at 655 cm-1. These signals can provide means to assess the conformation of disulfide bridges in proteins, otherwise difficult to investigate.