Coefficients of distribution of cyclic polyether macrotetrolide antibiotics between hydrophobic and hydrophilic solvents

Dependence of distribution of 14C-macrotetrolide antibiotics between water and chloroform on the presence of various additives in the aqueous phase was studied with the radioindicator procedure. It was shown that in comparison to distilled water aqueous solutions of chlorine salts of ammonium, potassium and sodium increased the content of macrotetrolides in chloroform as a result of forming strong hydrophobic complexes. This is especially applied to the ions of ammonium whose addition to the aqueous phase led to an increase of macrotetrolide level in chloroform up to 98.4 per cent. Addition of weak hydrochloric acid or alkaline agents resulted in marked transfer of the ionophores into the aqueous phase at the expense of hydrolysis of the antibiotic cyclic molecules. The highest hydrolysis levels were induced by potassium hydroxide, the content of the ionophores in the hydrophobic phase decreasing up to 90.6 per cent. The effect of picric acid on distribution of the macrotetrolides between water and chloroform was different and depended on its concentration.     

Carbon dioxide fixation by the mycelium of the actinomycete Streptomyces chrysomallus var. macrotetrolidi

The mycelium of Streptomyces chryzomallus var. macrotetrolidi producing the macrotetrolide antibiotic nonactin was shown to be capable of carbon dioxide fixation. Carbon was found to be incorporated into nonactin and macromolecular compounds in the biomass. Carbon was incorporated within 20 to 40 min of the mycelium incubation with NaH14CO3. Pyruvic and propionic acids stimulated carbon incorporation.     

The dependence of the distribution of ionophoric macrotetrolide antibiotics on the composition of their immiscible phases

Influence of various solvents on the content of macrotetrolides during their prolonged storage in solution was shown. Under the conditions of room temperature 90 per cent acetone induced hydrolysis of polyether antibiotics. 90 per cent ethanol and dry chloroform induced respectively slight and intensive cyclization of linear precursors (oxyacids). The study on distribution of macrotetrolides between immiscible phases of various composition revealed that addition of ethanol or acetone to the water-chloroform system of organic solvents induced the antibiotic liberation into the water phase which increased with increasing concentration of the substances being added. Inorganic cations intensified the process during either the oxyacid cyclization or the antibiotic hydrolysis and liberated the reaction products from the equilibrium mixture. Under such conditions the value of the ion radius or selectivity of the macrotetrolides to definite cations was in principle of no importance.     

Tensile trabeculae--myth or reality?

Understanding of the functional role of the trabecular bone is very important for the analysis and computer-aided simulations of bone remodelling processes. The aspired wide clinical applications remain a remote future despite a great number of developed up-to-date approaches and theories and collected data on both material properties of the trabecular bone and its reaction to various stimuli. It is widely accepted that the mechanical loading plays the major role for the structure of the cancellous bone. The in vivo loading conditions of the cancellous bone are not known. Hence, for the computer-aided analysis and modelling of the trabecular bone specimens, simplified loading conditions are used. Also for the analysis of the cancellous bone as a part of a whole bone simplified loading conditions are assumed based on previous research without questioning its accuracy or relevance to the real in vivo conditions. In particular, the bending loading of the bone, which originates from the well-known observations made more than a century ago that have evolved in the trajectorial theory or "tensile trabeculae tradition", is often assumed to reflect the physiological loading conditions of bones. Some studies show that the bending or tensile-compressive orthogonal loading conditions for the cancellous bone may lead to plausible results. However, some other research works suggest that the presence of the tensile trabecular structures (particularly in the proximal femur) is doubtful and the bending loading conditions in bone should be treated with caution. Moreover, the loading conditions with compensated (or minimised) bending also produce results that correlate with the material distribution in the bone. The purpose of this review is to analyse some of the data and ideas available in the literature and to discuss the question of the major factors that define the shape and structure of the trabecular bone during the process of functional adaptation.     

Principles of determination and verification of muscle forces in the human musculoskeletal system: Muscle forces to minimise bending stress

While there are a growing number of increasingly complex methodologies available to model geometry and material properties of bones, these models still cannot accurately describe physical behaviour of the skeletal system unless the boundary conditions, especially muscular loading, are correct. Available in vivo measurements of muscle forces are mostly highly invasive and offer no practical way to validate the outcome of any computational model that predicts muscle forces. However, muscle forces can be verified indirectly using the fundamental property of living tissue to functional adaptation and finite element (FE) analysis. Even though the mechanisms of the functional adaptation are not fully understood, its result is clearly seen in the shape and inner structure of bones. The FE method provides a precise tool for analysis of the stress/strain distribution in the bone under given loading conditions. The present work sets principles for the determination of the muscle forces on the basis of the widely accepted view that biological systems are optimized light-weight structures with minimised amount of unloaded/underloaded material and hence evenly distributed loading throughout the structure. Bending loading of bones is avoided/compensated in bones under physiological loading. Thus, bending minimisation provides the basis for the determination of the musculoskeletal system loading. As a result of our approach, the muscle forces for a human femur during normal gait and sitting down (peak hip joint force) are obtained such that the bone is loaded predominantly in compression and the stress distribution in proximal and diaphyseal femur corresponds to the material distribution in bone.     

Effect of organic acids on the biosynthesis of carotenes by an Actinomyces chrysomallus strain

Synthesis of carotenes by Actinomyces chrysomallus var. carotenoides was stimulated by citric, acetic, oxalacetic, fumaric, succinic, malic, alpha-ketoglutaric, tartaric, pyruvic, and propionic acids. Acetic acid acts as a precursor of carotene synthesis and also has another stimulating mechanism of action on carotenogenesis of the actinomycete. Acetic, furmaric, malic, succinic, and alpha-ketoglutaric acids stimulate cyclization of lycopene yielding beta-carotene.     

Ionophore characteristics of heliomycin]

A highly purified product, identified as a well-known antibiotic geliomycin, has been derived by gradient extraction of the mycelium from Streptomyces robefuscus isolated from soil specimens as a result of purposeful search for a producer of hydrophobic ionophore antibiotics. The ionophore properties of geliomycin are highly labile and inducible. Cationic or anionic nature and the angle of the function performed depend on the concentration, type of electrolyte, protocol of measurements, and some additives used for the preparation of geliomycin electrodes to measurements. Stable development of the cationic function was detected for potassium chloride. The lability of ionophore properties was the highest with ammonium chloride as the electrolyte. Ammonium acetate and potassium and sodium chlorides notably increased the stability of geliomycin electrodes. Selective activity of geliomycin towards potassium ion is a more permanent characteristic. The results permit a conclusion about the inducibility of ionophore properties of geliomycin, which may play an important role in the vital activity of the producer and manifest as a regulatory factor in maintenance of water and acid base balance.     

Directed synthesis of macrotetrolides

The composition of the macrotetrolide complex was found to be strongly dependent on the conditions of the Streptomyces chrysomallus v. macrotetrolidi cultivation and could be varied by including in the medium 0.2% of organic acids, precursors of macrotetrolides, such as acetic, propionic and succinic. Acetate caused an increase of the nonactin/monactin ratio, and no other homologues were detected. On the contrary, propionate and succinate produced a drop in the nonactin synthesis, which was accompanied by a rise in the amount of the higher homologues. The composition of the macrtetrolide mixture can also be changed by introducing in the cultivation medium specific inhibitors (100-200 micrograms/ml) such as malonate, cobalamin analogue, sulfadimesin. Malonate, an inhibitor of succinate dehydrogenase, increased the biosynthesis of higher ethylated homologues. Inhibition of methylmalonate mutase resulted in an increased yield of the methylated nonactin homologue and in a decreased yield of dinactin. In this case no other homologues were produced. The inhibitor of transmethylation, sulfadimesin, had no effect on the biosynthesis and composition of the macrotetralide mixture.