Placenta--a source of biologically active substances

In the review there are some data displaying the scientific and patent literature presenting placenta as a rich source of some biologically active substances (BAS): proteins, lipids, enzymes, glycolipids and glycolipoproteins, hormones. This information is capable to be used while developing the techniques of BAS producing from placenta in order of creating the organospecific complex preparations with medically-preventive properties.     

Alternative sources of biologically active substances

The majority of antibiotics and substances with diverse biological activity used in medicine are produced by actinomycetes, nonfilamentous bacteria and fungi. Other microorganisms, such as myxobacteria, pseudomonads, nocardias, basidiomycetes, marine microorganisms, enterobacteria, halobacteria, hyperthermophiles etc. are investigated for new biologically active metabolites.     

Receptor-based assays in screening for biologically active substances.

Molecular biology has identified new receptors and ligands which are deregulated in diseases such as cancer and autoimmune conditions and which provide rational targets for therapeutic intervention. Advances in instrumentation and methodology make it possible to screen large numbers of samples in simple receptor-ligand binding assays in the search for drug candidates. Caution must be exercised in the interpretation of data derived from such assays. This is particularly pertinent to the recently characterized receptors, such as the cytokine receptors, as we do not fully understand the relationship between the receptor type and the linkage of receptors to the appropriate or inappropriate second messenger systems that are used in the experimental screening protocols and the disease state.     

Polyelectrolyte microcapsules as the systems for delivery of biologically active substances

Based on the method of the layer-by-layer (LbL) adsorption of oppositely charged polyelectrolytes, sodium alginate (Alg) and poly-L-lysine (PLL), novel biodegradable microcapsules have been prepared for delivery of biological active substances (BAS). Porous spherical CaCO₃ microparticles were used as templates. The template cores were coated with several layers of oppositely charged polyelectrolytes forming shell on the core surface. The core-shell microparticles were converted into hollow microcapsules by means of core dissolution with EDTA. Mild conditions for microcapsules preparation allow to perform incorporation of various biomolecules maintaining their bioactivity. Biocompatibility and biodegradability of the polyelectrolytes give a possibility to use the microcapsules as the target delivery systems. Chymotrypsin entrapped into the microcapsules was used as a model enzyme. The immobilized enzyme retained about 86% of the activity compared to a native chymotrypsin. The resultant microcapsules were stable in acidic medium and could be easily decomposed by trypsin treatment in slightly alkaline medium. Chymotrypsin was shown to be active after its release from the microcapsules decomposed by the trypsin treatment. Thus, the microcapsules prepared by the LbL technique can be used for the development of new type of BAS delivery systems in humans and animals.     

PASS: prediction of activity spectra for biologically active substances

The concept of the biological activity spectrum was introduced to describe the properties of biologically active substances. The PASS (prediction of activity spectra for substances) software product, which predicts more than 300 pharmacological effects and biochemical mechanisms on the basis of the structural formula of a substance, may be efficiently used to find new targets (mechanisms) for some ligands and, conversely, to reveal new ligands for some biological targets. We have developed a WWW interface for the PASS software. A WWW server for the on-line prediction of the biological activity spectra of substances has been constructed.     

The effects of biologically active substances in medicinal plants on the metabolic activity of neutrophils

Neutrophils are the typical effector cells of the innate immune response because they are the first leukocytes to be recruited to an inflammatory site where they engulf invading microorganisms and destroy them by multiple oxidative and non-oxidative mechanisms. The destructive potential of neutrophils requires the tight control of their recruitment into tissue compartments and the production of inflammatory mediators such as reactive oxygen species. These oxidants can be highly toxic not only for infectious agents but also for neighbouring host tissues resulting in various autoimmune and inflammatory diseases. Thus, a significant attention in medicine is paid to approaches designed to modulate the metabolic activity of neutrophils. Synthetic steroid and non-steroid compounds with adverse side effects are commonly used for this purpose. The effects of natural substances which can modulate the metabolic activity of neutrophils and which simultaneously would not exert any significant unfavourable side effects have recently been investigated. Suitable candidates for this purpose might be compounds contained in herbs. These include especially polysaccharides and polyphenols, but also terpenes. The aim of the present paper is to summarize contemporary knowledge on the effects of compounds from herbs on the metabolic activity of mammalian neutrophils.     

The use of gel chromatography for the isolation of biologically active toxin complex from Bacillus anthrax

The multistep fractioning of the protein components from cultural filtrate of B. anthracis grown on casaminoacids containing medium was done. The scheme for preliminary purification of a toxin complex of B. anthracis against low and high molecular mass contaminants has been elaborated and includes ultrafiltration, gel chromatography in ultragel AcA-202 and TSK-gel toyopal HW-55. Biological activities of the complex,toxicity for laboratory animals and adenylate cyclase activity characteristic of B. anthracis toxin, are shown to remain intact in course of preliminary purification. Molecular masses of protein subunits from the fraction containing anthracis toxin activity reach 85-90 kD, 0.3-0.5 mg of toxin complex protein is yielded from 1 l of B. anthracis cultural filtrate.     

Low doses of biologically active substances: effects, possible mechanisms, and features

Some substances can produce a response in biological systems at extraordinarily low concentrations. Often called the 'low' or 'small' dose effect, the meaning or definition of what is meant by 'low' in this context is discussed. For the purposes of this article the expression is taken to be a concentration substantially below the equilibrium dissociation constant of the effector-target complex, but extremely low concentrations (<10(-19) m) are excluded from consideration. The main features of very low or 'small' dose action are described. Possible mechanisms of the effects of very low doses are suggested. The main thrust of the paper concerns the explanation of bimodal and polymodal dose-effect curves. A general formal kinetic model for such curves and its application will be discussed.     

Chemically defined medium for the production of biologically active substances of CHO cells

A recombinant CHO cell line (GT19) secreting a high level of human growth hormone (hGH) was constructed with amplification of the introduced hGH gene. The cells grew well in the alpha MEM medium supplemented with 5% dialyzed fetal calf serum (dFCS), but not with less than 1% dFCS. Therefore we examined various medium components and obtained an improved medium which supported cell growth at low serum concentrations. The production of hGH by the cells was also enhanced in this medium.Abbreviations CHO Chinese hamster ovary - hGH human growth hormone - dFCS dialyzed fetal calf serum - dhfr dihydroforate reductase - MTX methotrexate     

Quantitative NMR spectroscopy of biologically active substances and excipients

Biologically active ingredients and excipients are the essentials of a drug formulation, such as a tablet, dragee, solution, etc. Quality control of such substances thus plays a pivotal role in the production process of pharmaceutical drugs. Since these agents often exhibit complex structures, consist of multiple components, or lack of a chromophore, traditional means of characterization are often not feasible. Furthermore, substances of small molecular weight or strong polar character generally exhibit poor chromatographic properties, thus, conventional procedures such as high-performance liquid chromatography are often not applicable. Instead, quantitative nuclear magnetic resonance (qNMR) spectroscopy has emerged as an alternative or orthogonal method in drug analysis. In this review, we elaborate on the application of qNMR to three important classes of biological substances, namely polysaccharides, amino acids, and lipids, and demonstrate the benefits of this modern tool in contrast to traditional techniques.     

Obtaining liposomal preparations of various biologically active substances by the method of detergent flow analysis]

It was shown that detergent dialysis could be successfully used for liposomal encapsulation of substances belonging to different chemical groups with diverse therapeutic activity such as rifampicin, aclarubicin, amphotericin B, pefloxacin and insulin. Liposome encapsulation of substances poorly soluble or insoluble in aqueous media was likely the most promising. The optimal incorporation depended on both the composition of the lipids forming the liposomes and the properties of the compounds being encapsulated.     

The use of enzymes for searching for biologically active compounds

Possible use of extracellular staphylococcal DNAase in screening substances with potential antibacterial activity was studied on quinoxalin as an example. For screening substances with antiviral activity the possible use of the influenza virus neuraminidase was studied on fluoren as an example. Close correlation between the biological activity of quinoxalin derivatives and the ability to inhibit DNAase was revealed. The most active inhibitors of the enzyme were dioxidin and other biologically active analogs of quinoxalin 1,4-di-N-oxide. The use of the extracellular nuclease as a biochemical model permitted to establish the structure/function dependence with respect to the quinoxalin derivatives. The effect of the fluoren derivatives on activity of the influenza virus neuramididase was studied. It was shown that florenal, an antiviral drug inhibited the virus specific enzyme by 80 to 90 per cent and had no effect on catalytic activity of bacterial neuraminidase. Biologically inactive and slightly active derivatives of the compounds did not inhibit the influenza virus enzyme. At the same time some of them lowered the activity of the bacterial enzyme.     

Principles of dissociation of complex spectra of biologically active substances into bands corresponding to separate electron transitions

General principles of spectroscopic deconvolution of complex spectra into bands that correspond to separate electronic transitions are considered. Any spectroscopic deconvolution should be based on a physical model. The absence of the physical model makes the deconvolution senseless. The methods of postulation of physical models and their refinement resulting from self-consistent deconvolutions are discussed. We have performed deconvolutions of absorption spectra of different ionic and tautomeric forms of pyridoxamine, pyridoxamine-5'-phosphate, pyridoxal, pyridoxal-5'-phosphate, common nucleic bases and their nucleosides. The results of the above-mentioned deconvolutions, as well as the serviceable program that allows to carry out such deconvolutions and recommendations for its usage are presented.     

Evidence for several types of biologically active substances in north pacific sea anemones

1. Twenty-two sea anemone samples from seven species were collected in Aleutian and Comandorskiye Islands from sub-littoral region (> 50 m depth).2. Water-ethanol extracts of sea anemones were tested using various test-systems after ethanol evaporation.3. All sea anemones extracts inhibited DNA and most of them inhibited RNA synthesis in Ehrlich carcinoma tumor cells.4. Extracts of most sea anemones species showed high hemolytic activity.5. The extracts proved to be nontoxic or display low toxicity being i.p. injected into mice.6. Some extracts precipitated virus of aleutian disease of mink.7. None of the extracts showed activity toward Gram + ve, Gram −ve bacteria or yeast.