Cyclosporin A as a model antigen: immunochemical and structural studies

The immunosuppressant drug cyclosporin (Cs) A is a cyclic undecapeptide which has been used as a model antigen because structural information and a large number of analogs, modified at each of its 11 positions, were available. This review summarizes immunochemical and crystallographic studies of the interaction between the Fab of monoclonal antibody R45-45-11 and Cs. Three points are discussed: (1) the different conformations of CsA and the question of its biologically active form; (2) the Fab-CsA recognition mechanism; and (3) the relationship between structure and binding properties of CsA analogs.     

Correlation of biophysical parameters of biologically active points and variations of heliogeophysical factors

The correlation between the parameters of biologically active points and the dynamics of solar activity was studied. Statistically significant correlations between electroconductivity of biologically active points and solar activity indices (sunspot number, Ap-index, solar radiowave flux) were revealed. The spectral analysis of the temporal organization of biologically active points revealed a set of periods present in the dynamics of solar activity. It was concluded that bioelectric system of the human organism is a complicated multilevel time-structure, which effectively reacts to changes in heliogeophysical dynamics. The bioelectric system of biologically active points is considered to be one of general information channels of electromagnetic nature, which realize the connection of organism with environment.     

Predicting the unpredictable: Recent structure–activity studies on peptide-based macrocycles

Heterocycle-containing macrocycles are an emerging class of molecules that have therapeutic efficacy. Many biologically active natural products that have interesting biological properties fall into this class of molecules. The highly specific and selective biological activity is often attributed to the unique conformation of these macrocycles, which is affected by the elements of the macrocycles as well as its surroundings in biological systems. In this review, the structure–activity relationship studies of several recently developed biologically active heterocycle-containing macrocycles have been discussed in order to facilitate an understanding on how unpredictable structures can be controlled.     

Empleo de un nuevo protocolo de extracción y disminución de las falsas hiperprolactinemias

IntroductionNumerous authors have reported that prolactin measurement is influenced by several factors and consequently the values obtained may not faithfully reflect the physiological reality of the individual studied. Unless a series of measures is adopted, especially in the pre-analytic stage, values may be falsely elevated. The objective of the present study was to evaluate the extent to which optimization or non-optimization of the extraction procedure translates into higher results and how reports expressed in terms of monomeric (biologically active) prolactin could be crucial to adopt a diagnosis and therapeutic approach.Material and methodsWe performed two extractions in each woman (following the protocol universally used for this kind of analysis): one through direct puncture and another 60 min later without a new puncture (a catheter was inserted in the site of the first puncture and kept permeable by salinization). The monomeric fraction was then studied, if required.ResultsA statistically significant difference was observed between the 2 extractions. The monomeric fraction was three times lower in the second extraction than in the first.DiscussionThe results of this study justify systematic use of extraction techniques that avoid the stress of venous puncture, as well as the use of the term biologically active prolactin [monomeric (little) prolactin fraction] in reports.     

The effect of laser puncture on the functional indices of the mammalian body

Biologically active points (acupuncture points) and reflexogenic zones of Wistar rats of different age were exposed to He-Ne laser radiation with the subsequent control of acetylcholine esterase activity, electric parameters of skeletal muscles and heart, and physical activity. Laser puncture was shown to increase the sympathetic nervous system tonus which was manifested by the decreased acetylcholine esterase activity and increased heart rate. Laser puncture stimulated the growth of membrane potential and increased considerably the performance capability of animals, particularly of three-month-olds.     

Hyperexpression and purification of biologically active human luteinizing hormone and human chorionic gonadotropin using the methylotropic yeast, Pichia pastoris

The glycoprotein hormones, luteinizing hormone (LH), human chorionic gonadotropin (hCG), thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH), play important roles in overall physiology and reproduction. These hormones are heterodimeric molecules consisting of an identical alpha subunit non-covalently associated with the hormone-specific beta subunit. The inherent structural intricacies possessed by these hormones make them very interesting model systems for structure-function relationship studies of complex dimeric glycoproteins. The structural studies, as well as, the therapeutic applications require large quantities of biologically active hormones free of any contaminants. In this study, we report hyperexpression and purification of biologically active recombinant hLH and hCG expressed using Pichia pastoris expression system. A combination of hydrophobic interaction chromatography and ion exchange chromatography has been used to purify these recombinant hormones to homogeneity. Using a number of biochemical and immunological criteria, the recombinant hormones have been shown to be similar to the natural hormones and were equally biologically active. The preliminary data also suggested that P. pastoris cells express a low molecular weight isoform of hCG that appeared to be less glycosylated. This isoform exhibited lesser affinity for the receptor as compared to hCG, but was found to be fully biologically active.     

Experimental evaluation of the effectiveness of wound dressings based on biologically active substances from marine hydrobionts

This article presents the experimental data on the testing of new wound dressings, viz., porous plates, prepared on the basis of chitosan and calcium alginate that contain biologically active substances (BASs) derived from marine hydrobionts. In a burn wound model in guinea pigs, we revealed a positive effect of tested samples of wound dressings on the wound-healing process; the data of planimetric and pathomorphological studies showing the acceleration of the process of regeneration in the wound are discussed. It was noted that the dynamics and patomorphological characteristics of the wound healing process differed depending on the structure of the BAS included into the composition of wound dressings (peptides, sulfated polysaccharides, a complex of amino acids and peptides).     

Patient autonomy naturalized

Traditional informed consent often promotes passive acquiescence rather than active exercise of autonomy. A more natural biologically based model of autonomy is needed, a model that both recognizes the biological roots and therapeutic benefits of active confident choices among real alternatives, and offers substantive guidelines for promoting patient autonomy. A biological model of patient autonomy explains the value of information to patients, outlines the circumstances under which patients make effective choices, and suggests complementary roles for patients and professional caregivers.     

The logic of biologically active small molecules: amazing ability of microorganisms*

In this review article, I will outline my way of thinking about biologically active small molecules. The structure of liposidomycin B from Streptomyces species resulted in my initial sense that a structure tells its function. A biologically active small molecule may save directly or indirectly a number of people. Even if the molecule has not been used as a therapeutic agent, it can be used as a useful chemical probe for dissecting a living cell into different biochemical pieces. Such biologically active small molecules derived from microorganisms have been primarily found in cultivable microorganisms that make up only 1% of total microbes in nature. Discovery of novel growth factors, zincmethylphyrin, zinc coproporphyrin, and coproporphyrin enabled laboratory cultivation of previously uncultured Leucobacter sp. These findings might expand the possibility for further discovery of novel therapeutic agents or chemical probes.     

Physiologically adequate experimental model of aggression and emotional stress

A simple adequate experimental model of aggression and emotional stress has been elaborated, based on mild fixation of rats tails in the cage wall. It is shown that in a group of rats, in these conditions a continuous aggressive behaviour arises, leading to the development of emotional stress. The elaborated experimental model has no defects, characteristic of other models of aggression and stress. It demands neither a prolonged training of animals nor special expensive equipment; it allows simultaneous use in experiments of a great number of animals, creates conditions for natural aggressive-defensive behaviour of rats without provoking artificial manipulations. The proposed model allows to study the pathogenesis of emotional stress, mechanisms of resistivity and predisposition to it and also search and testing of biologically active substances, enhancing resistance to emotional stress.     

垂体腺苷酸环化酶激活肽的研究概况

垂体腺苷酸环化酶激活肽（PACAP）及其受体存在于许多动物的下丘脑和垂体中,而且在肾上腺、睾丸、卵巢、肝脏、肾脏、胰腺、松果腺、心脏、脊椎、神经节、呼吸系统和消化系统等组织或系统中也存在,其中肾上腺含量最高.在这些组织或系统中,通过Ca²⁺、Na⁺、腺苷酸环化酶或磷酸肌醇等作用通路,PACAP发挥神经递质/调质、或神经营养因子等生物学功能.     

Supraspinal connections of the reproductive organs: structural and functional aspects

Gonadal functions are governed by the hypothalamo-hypophyseal system. Other organs of the reproduction tract are under the regulatory action of gonadal steroids. In the past two decades several data have been accumulated on the involvement of fine-tuning control mechanisms which include autocrine and paracrine effects of biologically active substances produced locally and the regulatory action of nerves innervating the organs of the system. Recent studies using the viral transsynaptic technique have revealed cell groups in the central nervous system that are transneuronally connected with the male and female reproductive organs. This review summarizes neuromorphological data on the supraspinal innervation of reproductive organs and the functional significance of these brain areas in the control of reproduction.     

The human body response to factors related to solar activity variations

The effect of nonstationary solar processes on human organism was studied. Daily measurements of electrical conductivity of 22 biologically active points on human skin, arterial pressure, and pulse frequency of 30 persons were performed, and their subjective sensations were registered. A comparative analysis of the data and variations in environment parameters, such as local A-index, atmospheric pressure, temperature, and indices of cosmic rays indicated a coincidence of their main periods. The conclusion is made that the reaction of the human organism on abrupt solar disturbances is biphasic and that there is a semiannual wave of synchronization of work of internal organs. The results are confirmed by simultaneous measurements in different cities.     

Allergenic properties of the substance produced by the Streptococcus strain sp. Thom-1606

The newly isolated biologically active agent "STP" (the substance produced by Streptococcus strain sp. TOM-1606) has been found to possess no allergenic properties. This new preparation has shown hyposensitizing activity on the level with the allergen. The morphological data obtained in the study of the organs of experimental animals have revealed the immunostimulating action of preparation "STP" on the body, that is confirmed by the characteristic transformation of the internal organs of experimental animals.     

Effect of Plants Synthesizing Biologically Active Substances—Precocenes—on Insects

Integrated data on the direct and indirect influence of plants synthesizing biologically active substances—precocenes—on phytophagous insects developing and feeding on these plants are presented. The experimental data on individual organs and tissues as well as organ systems in various insect groups are discussed.     

Novel GSK-3beta inhibitors from sequential virtual screening

Glycogen synthase kinase-3 (GSK-3beta) has been emerging as a key therapeutic target for type-2 diabetics, Alzheimer's disease, cancer, and chronic inflammation. For the purpose of finding biologically active and novel compounds and providing new idea for drug-design, we performed virtual screening using commercially available database. Three-dimensional common feature pharmacophore model was developed by using HipHop program provided in Catalyst software and it was used as a query for screening database. Recursive partitioning (RP) model was developed as a filtering system, which was able to classify active and inactive compounds. Eventually, a sequential virtual screening procedure (SQSP) was conducted by applying the common feature pharmacophore and RP model in succession to discover novel potent GSK-3beta inhibitors. The final 56 hit compounds were carefully selected considering predicted docking mode in crystal structures. Subsequent enzyme assay for human GSK-3beta protein confirmed that three compounds of these hit compounds exhibit micromolar inhibitory activity. Here, we report novel hit compounds and their binding mode in the active site of GSK-3beta crystal structure.     

Pharynx regeneration in planarians

The obtained and published data on pharynx regeneration in planarians have been reviewed. Planarians can regenerate from a small body fragment and restore all missing organs including the pharynx. The pharynx is a relatively autonomous organ with a differentiated structure and specialized function. Pharynx regeneration has specific features, and its studies are of considerable theoretical interest. Pharynx regeneration can also be a convenient model to study the molecular mechanisms of regeneration that remain undisclosed. In addition, this model can be used to test biologically active compounds in order to elucidate their effect on morphogenesis. This subject of investigation benefits by a simpler and more adequate analysis as well as a possibility to use large numbers of animals and small quantities of analyzed substances.     

Prediction of gastric ulcers based on the change in electrical resistance of acupuncture points using fuzzy logic decision-making

Many theories of reflexology use ancient concepts which do not coincide with the modern medical terminology of anatomy, physiology and biophysics. This substantially reduces the trust of physicians in reflexology methods. During this research, several mathematical models for the interaction of the internal and biological active points of meridian structures have been proposed. The analysis of these models allows the specification of a list of gastric diseases for which reflex diagnostics and reflex therapy methods are most effective and also allows increasing the effectiveness of these procedures. It is shown that good results for the prediction and early diagnosis of diseases from the reaction energy of biologically active points (acupuncture points) are obtained using fuzzy logic decision making.     

Ghrelin—a novel generation of anti‐obesity drug: design,pharmacomodulation and biological activity of ghrelin analogues

Ghrelin is a unique bioactive peptide with respect to both the structure and its biological function. This 28‐amino acid peptide is modified with an n‐octanoyl group at serine‐3, and accordingly is the only lipidated biologically active peptide hormone known so far. Ghrelin binds to the so‐called ghrelin or GHS receptor, a member of the class A of G‐protein coupled receptors, which leads to Ca²⁺ release intracellularly due to the activation of the Gq‐system. Interestingly, the ghrelin receptor shows a significant constitutive activity which means that in addition to agonists and antagonists, inverse agonists play an important role in receptor modulation. In this review, the major activities of ghrelin are summarized with a strong focus on the regulation of food intake. So far reported agonists, antagonists and inverse agonists are shown and structure activitiy relationships are discussed. Furthermore, the application of ghrelin ligands as novel anti‐obesity drugs is outlined and the state of the art in this field is summarized. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.