Ensembles of carboxymethyl cyclodextrins on cationic liposomes as highly efficient nanocontainers for the delivery of hydrophobic compounds

The increase of payload is one of the key tasks in creation of nanocontainers for the delivery of bioactive substances (BAS). In this work the adsorption of anionic carboxymethyl cyclodextrins (CMCDs) on the surface of cationic liposomes was studied as mechanism of formation of capacious nanocontainers for the encapsulation and delivery of hydrophobic BAS. The formation and physico-chemical characteristics of complexes were studied by means of laser microelectrophoresis, dynamic light-scattering, conductometry and atomic force microscopy (AFM). As a model, bioactive molecule hydrophobic curcumin was chosen for the investigation. The encapsulation of curcumin was controlled by UV–Vis spectrometry. Interaction of CMCDs/liposomes complexes with model cell membranes was visualized by fluorescent microscopy. Finally, cytotoxicity of nanocontainers was studied by MTT-test. It was estimated that colloid stable complexes with net positive charge could contain up to 2.5÷5 CMCD molecules per one cationic lipid. Incorporation of curcumin in CMCDs does not change the character of interaction of oligosaccharides with liposomal membranes of individual liposome. CMCDs/liposomes complexes adsorb on model cell membranes without significant loss of CMCD molecules. This fact in addition to low cytotoxicity of cationic CMCDs/liposomes complexes demonstrates potential of their application as nanovehicles for the delivery of BAS.     

Preparation and characterization of antioxidant nanospheres from multiple α-lipoic acid-containing compounds

The purpose of this study was to prepare and characterize antioxidant nanospheres composed of multiple α-lipoic acid-containing compounds (mALAs). It was found that the nanospheres were remarkably stable under physiologic conditions, maintained the antioxidant property of α-lipoic acid, and could be destabilized oxidatively and enzymatically. The preparations were simple and highly reproducible providing a new strategy for the development of nanometer-sized antioxidant biomaterials. The nanospheres may find applications as antioxidant therapeutics and oxidation-responsive antioxidant nanocontainers in drug delivery for pathological conditions characterized by oxidative stress including cancer and neurodegenerative diseases.     

Endocrine functions of brain in adult and developing mammals

The main prerequisite for organism’s viability is the maintenance of the internal environment despite changes in the external environment, which is provided by the neuroendocrine control system. The key unit in this system is hypothalamus exerting endocrine effects on certain peripheral organs and anterior pituitary. Physiologically active substances of neuronal origin enter blood vessels in the neurohemal parts of hypothalamus where no blood-brain barrier exists. In other parts of the adult brain, the arrival of physiologically active substances is blocked by the blood-brain barrier. According to the generally accepted concept, the neuroendocrine system formation in ontogeny starts with the maturation of peripheral endocrine glands, which initially function autonomously and then are controlled by the anterior pituitary. The brain is engaged in neuroendocrine control after its maturation completes, which results in a closed control system typical of adult mammals. Since neurons start to secrete physiologically active substances soon after their formation and long before interneuronal connections are formed, these cells are thought to have an effect on brain development as inducers. Considering that there is no blood-brain barrier during this period, we proposed the hypothesis that the developing brain functions as a multipotent endocrine organ. This means that tens of physiologically active substances arrive from the brain to the systemic circulation and have an endocrine effect on the whole body development. Dopamine, serotonin, and gonadotropin-releasing hormone were selected as marker physiologically active substances of cerebral origin to test this hypothesis. In adult animals, they act as neurotransmitters or neuromodulators transmitting information from neuron to neuron as well as neurohormones arriving from the hypothalamus with portal blood to the anterior pituitary. Perinatal rats—before the blood-brain barrier is formed—proved to have equally high concentration of dopamine, serotonin, and gonadotropin-releasing hormone in the systemic circulation as in the adult portal system. After the brain-blood barrier is formed, the blood concentration of dopamine and gonadotropin-releasing hormone drops to zero, which indirectly confirms their cerebral origin. Moreover, the decrease in the blood concentration of dopamine, serotonin, and gonadotropin-releasing hormone before the brain-blood barrier formation after the microsurgical disruption of neurons that synthesize them or inhibition of dopamine and serotonin synthesis in the brain directly confirm their cerebral origin. Before the blood-brain barrier formation, dopamine, serotonin, gonadotropin-releasing hormone, and likely many other physiologically active substances of cerebral origin can have endocrine effects on peripheral target organs—anterior pituitary, gonads, kidney, heart, blood vessels, and the proper brain. Although the period of brain functioning as an endocrine organ is not long, it is crucial for the body development since physiologically active substances exert irreversible effects on the targets as morphogenetic factors during this period. Thus, the developing brain from the neuron formation to the establishment of the blood-brain barrier functions as a multipotent endocrine organ participating in endocrine control of the whole body development.     

Biological tests of physiologically active compounds (approaches): Communication II

This review considers the methods of investigation proposed by L. A. Piruzyan in the field of preclinical trials of physiologically active compounds: (1) the search for new physiologically active compounds illustrated by analysis of the developmental mechanisms of some diseases, such as jaundice of the newborn, renal and liver insufficiency, acute drug-induced intoxication, discoid and systemic lupus erythematosus, and lupus-like syndrome; (2) experimental studies on safety of medicinal substances—the testing of substances for mutagenicity and embryotoxicity, the preparation of compounds with antimutagenic and anticarcinogenic properties, the determination of preserved blood characteristics; (3) the stabilization of medicinal preparations for use—with drug oxidation inhibitors, and substances contained in liposomes. The ligand pathology concept is presented. The necessity of an individualized approach for assessment of chemical compound safety for humans in emphasized: it should be based on the activity determination of certain enzymes in each subject. Deceased.     

The effect of a neurotransplant of embryonal tissue on reactive processes during brain trauma in rats

The effect of embryonic brain tissue on reactive processes in injured brain of adult rats has been studied. The transplant can prevent development of inflammatory loci which are formed after deep double brain trauma. The transplant is supposed to excrete physiologically active compounds which either suppress the development of immunological conflict in the injured brain or activate blood and brain suppressor mechanisms.     

Metabolic function of the lungs and regulation of homeostasis

Morphological, biochemical and pathophysiological data on the significance of the metabolic (non-respiratory) function of the lungs in the regulation of homeostasis have been summarized. The key "strategic" position of the lungs in the blood circulation system, the concentration of a unique set of biochemical regulatory factors in the lung endothelium, as well the presence of a multiple system of nervous and humoral control ensure the realization of a specific mission by lungs as a regulator of the functional integrity of the organism. The lungs serve as a barrier controlling the passage of deleterious substances into arterial blood and consequently into the brain and other organs and at the same time the lungs are responsible for the controlled synthesis and elimination of physiologically active substances essential for the work of the same systems. These functions attain special significance under stress-induced situations as a result of homeostatic disruptions and as a consequence of grave extrapulmonary injuries. The author's concept on a compensatory function of the lung kallikrein-kinin system under extreme conditions of organism is given. This pathway opens up the prospects for search of ways of correcting functional disruption in organism.     

Hypotensive activity of the plasma proteins in a normovolemic blood exchange transfusion

The effect of post-hemotransfusion protein fractions on blood pressure, microcirculation and physiologically active substances has been studied in stimulated blood replacement by homologous animal blood. The in vivo and in vitro experiments have revealed that subfraction of hemotransfusion plasma macromolecular proteins has a prominent antihypertensive effect, leading to blood flow slowing in the microvascular bed. Hemotransfusion plasma proteins possess high serotonin-releasing activity. The involvement of blood proteins and physiologically active substances into the generation of the recepient's response to homologous blood transfusion from several donors and its role in the genesis of post-transfusion complications are discussed.     

Triterpene glycosides and the structural-functional properties of membranes

Triterpene glycosides have been found in many plant species and some marine animals. Many of these compounds are physiologically active and possess a broad range of medico-biological action. The physiological activity of triterpene glycosides is based on their ability to interact with the components of biological systems, primarily with sterols comprising the structure of biomembranes. The interaction of glycosides with sterols causes disturbance of selective permeability in plasmic membranes. Triterpene glycosides affect the liposome ionic permeability and flat bilayer lipid membranes. The rate of glycoside effect depends on quantitative and qualitative sterol level in the membrane. These compounds are used by organisms in the struggle for life and in maintaining the biological equilibrium in the antagonistic interactions of biological systems and ensure plant immunity against fungal diseases. Triterpene glycosides as substances of exogenous origin exhibit physiological activity towards warm-blooded animals. They affect the metabolism, the functional state of the organs and the organism as a whole.     

Surface modified dendrimers: synthesis and characterization for cancer targeted drug delivery

Dendrimers represents a highly branched three-dimensional structure that provides a high degree of surface functionality and versatility. PAMAM dendrimers are used as well-defined nanocontainers to conjugate, complex or encapsulate therapeutic drugs or imaging moieties. Star-burst [PAMAM] dendrimers represent a superior carrier platform for drug delivery. The present study was aimed at synthesis of a surface modified dendrimer for cancer targeted drug delivery system. For this 4.0 G PAMAM dendrimer was conjugated with Gallic acid [GA] and characterized through UV, IR, 1H NMR and mass spectroscopy. Cytotoxicity study of dendrimer conjugate was carried out against MCF-7 cell line using MTT assay. The study revealed that the conjugate is active against MCF-7 cell line and might act synergistically with anti-cancer drug and gallic acid-dendrimer conjugate might be a promising nano-platform for cancer targeting and cancer diagnosis.     

Initiated Oxidation of Phosphatidylcholine Liposomes with Some Functional Nutraceuticals

Russian Journal of Bioorganic Chemistry - Design and research of liposome structures on the basis of soy phosphatidylcholine (PC) as nanocontainers for delivery of various functional nutraceuticals...     

Experimental bases and prospects for the use of humic acid preparations from peat in medicine and agricultural production]

The analysis of action of physiologically active peat substances--a complex of humic acids is given. Using the pharmaco-biological tests and modelling of the diseases a high antitoxic effect of sodium humate and possibility to use it in medicine, veterinary science and animal husbandry as nonspecific pharmacy raising the organism resistance to the action of different unfavourable factors is proved.     

Endocrine function of the heart: structuro-functional aspects

Modern notions, accumulated during the period of investigation of before poorly studied endocrine++ function of the heart are presented. History of the problem, structural and functional aspects on argumentation of the cardiac endocrine function, place and role of physiologically active cardiac peptides in regulation of liquor and electrolytic homeostasis are followed, as well as interactions of the cardiac endocrine apparatus with the hormonal system of the organism. The authors' experience on the investigation connected with the problem is also demonstrated.     

柑桔果实中柠檬苦素类化合物的研究现状与展望

柠檬苦素类似物（ｌｉｍｏｎｏｉｄ）是三萜类的植物次生代谢产物,主要存在于芸香科和楝科植物中。柠檬苦素（ｌｉｍｏｎｉｎ）及其类似物存在于柑桔属（Ｃｉｔｒｕｓ）的多种植物中。至今已从柑桔属植物中分离出３６种柠檬苦素类似物及１７种柠檬苦素类似物配糖体。柑桔中苦味原因之一为柠檬苦素类似物。作为其代表具有强烈苦味的柠檬苦素和诺米林如果在柑桔果汁中含量超过６ｍｇ／Ｌ,那么这种柑桔用于饮食业已不适合［１］。近年来,笔者对柑桔果实中的柠檬苦素类似物的生理变化及生物合成作过系统研究［１～９］,并提出将柠檬苦素类似…     

The Prospect and Current Studies on the Limonoids in Citrus

Limonoids are a group of triterpenoids found in Rutaceae and Meliaceae. Limonoids of citrus are excellent physiologically active compounds. In this paper, we report the biochemical study and biological recovery of limonoids in citrus fruits.     

Investigation of antioxidant activity of quinoline thioderivatives

Antioxidant activity of new synthetic physiologically active substances (thioderivatives of quinoline) are investigated using the complex of primary estimation techniques in vitro and in vivo. It is shown that the compounds investigated display both antiradical and anti-oxidative activity, most strongly delineated for the compounds with methoxygroup in the 6th position of quinoline cycle. The suppositions concerning the mechanism of their antioxidant activity are made.     

Signal molecules during the organism development: Central and peripheral sources of noradrenaline in rat ontogenesis

Using the method of high performance liquid chromatography with electrochemical detection, the age dynamics of the content of noradrenaline (NA) in the brain, adrenal gland, and the organ of Zuckerkandl in prenatal (18th and 21st days of embryogenesis) and early postnatal (3, 7, 15, and 30th days) periods of development was studied. The potential contribution of these organs to the formation of physiologically active concentration of noradrenalin in the blood was also assessed. The results suggest that, during the development of the organism, the activity of the sources of noradrenaline in the general circulation changes, which gives a reason to assume the existence of humoral interaction between NA-producing organs in the perinatal period of ontogenesis.     

Parameters characterizing the productivity of an inoculum of the producer of oleandomycin

The possibility of using different criteria for estimation of the productivity of the vegetative inoculum of the oleandomycin-producing organism was studied with a purpose of providing maximum levels of the biosynthetic process. The use of the criteria of the culture respiration intensity and accumulation of the physiologically active mycelium as the main ones was shown to be advisable. The quantity and distribution of the mycelium in samples and the time course of changes in active acidity of the medium during the inoculum growth may be used as auxiliary criteria.     

Hormones and the levels of humoral regulation]

The problems on the place of hormones secreted by "classical" endocrine glands, on their relationship with other compounds that possess physiological activity, criteria that determine the definition "hormone" are considered in this article. The conception about the levels of the humoral regulatory systems that are organized and formed during phylogenesis and ontogenesis and provide a consecutive increase in their complexity and mobility of adaptation to changes of environment and internal conditions are substantiated on the basis of numerous data. The metabolites that are products of nonspecific activity of any cell of the multicellular organism form the first and simplest level of humoral regulatory organization. The next (second) level of humoral organization is also formed by chemically simple substances. However, these substances are specialized products of the secretory activity of cells and exert potent influence on the physiological processes. Neuroamines and regulatory peptides are applied to these agents, in the first place. They arise simultaneously and jointly at the first stage of ontogenesis. The distinctive characters of the third level of the humoral regulation are increased and complication of the regulatory activity conditioned by cooperative influences of humoral agents produced by single secretory elements situated outside the classical endocrine glands. The chemically and originally different substances causing predominantly local effects are attributed to these physiologically active substances. Their participation in general adaptive reactions as well as inclusion of classical hormones into hierarchy of humoral regulation signify the formation of the forth regulatory level that provides realization of general homeostatic reactions peculiar to the whole organism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flash photolysis of caged compounds in the cilia of olfactory sensory neurons

Photolysis of caged compounds allows the production of rapid and localized increases in the concentration of various physiologically active compounds. Caged compounds are molecules made physiologically inactive by a chemical cage that can be broken by a flash of ultraviolet light. Here, we show how to obtain patch-clamp recordings combined with photolysis of caged compounds for the study of olfactory transduction in dissociated mouse olfactory sensory neurons. The process of olfactory transduction (Figure 1) takes place in the cilia of olfactory sensory neurons, where odorant binding to receptors leads to the increase of cAMP that opens cyclic nucleotide-gated (CNG) channels. Ca entry through CNG channels activates Ca-activated Cl channels. We show how to dissociate neurons from the mouse olfactory epithelium and how to activate CNG channels or Ca-activated Cl channels by photolysis of caged cAMP or caged Ca. We use a flash lamp to apply ultraviolet flashes to the ciliary region to uncage cAMP or Ca while patch-clamp recordings are taken to measure the current in the whole-cell voltage-clamp configuration.     

Chemical Features of Medicinal Plants (Review)

Data on chemical composition related to the synthesis of physiologically active substances (alkaloids, terpenoids, glycosides, phenolic compounds, etc.) and to the accumulation of individual elements or groups of five to ten elements (e.g., Cr, Co, Mn, and Zn) in medicinal plants were reviewed. Chemical features of medicinal plants serve as an integral determinant of their species specificity and pharmacological properties and enable their wide use in medical practice. The relationship between the synthesis of physiologically active substances and accumulation of elements is mediated by several levels of molecular regulation.