Substances In Biological Systems Research Articles

Detection of ascorbic acid by persistent luminescent nanoparticles based on CoOOH nanosheets modification.

Persistent luminescent nanomaterials (PLNPs) Zn0.8Ga2O4: Cr3+, Zr3+ with high brightness and good dispersion were prepared by hydrothermal method. The PLNPs were used as luminescent units, and CoOOH nanosheets were used as quenching agents. Based on the fluorescence internal filtering effect, the luminescence of PLNPs were effectively quenched by CoOOH modification on the surface of PLNPs. However, the introduction of ascorbic acid (AA) restored the luminescence of PLNPs and successfully achieved highly sensitive and selective detection of AA. This was due to a selective redox reaction between CoOOH and AA, in which CoOOH was reduced to Co2+. The degree of luminescence recovery of PLNPs showed a good linear relationship with AA concentration in the range 5-250 µM, with a detection limit of 0.72 µM. Therecovery of actualspikedsamples were 97.9-102.2%. This method isexpected to provide reference for the study of other redox substances in biological systems.

Fluorescent probe for sensitive discrimination of GSH and Hcy/Cys with single-wavelength excitation in biological systems via different emission

Biothiols (GSH, Hcy, Cys) are important active sulfur substances in biological systems and widely participate in various physiological processes. The three kinds of biothiols have similar chemical structures, including the sulfhydryl group (-SH) and an amino group (-NH2), so distinguishing two or more of them simultaneously is an important challenge. Herein, a nopinone-based fluorescent probe 3-(3-((4-nitrobenzoxadiazole vinyl) nopinyl difluoride (NF-NBD) was designed to distinguish GSH and Hcy/Cys by generating different fluorescence channels with a single excitation wavelength. The nitrobenzodioxazole (NBD) was introduced in the fluorescent probe by ether bounds that can quench fluorescence and selectively discriminate GSH and Hcy/Cys. After reacting with GSH and Hcy/Cys, NF-NBD exhibited strong fluorescence (green for GSH and yellow for Hcy/Cys). NF-NBD displayed a wide linear range, low detection limit, a rapid response time, and superior selectivity for biothiols. Furthermore, NF-NBD was applied to image and distinguish different biothiols in living cells and zebrafish via different fluorescence signals at a single excitation wavelength.

Based ‘successive’ nucleophilic substitution mitochondrial-targeted H2S red light emissive fluorescent probe and its imaging in mice

The research of endogenous hydrogen sulfide (H2S) biology function, pathological and pharmacological effects has been active in the field of chemists and biologists in recent years. Especially, consequent H2S detection mechanisms and biological applications based on fluorescence probe emerged in endlessly, competing ideas, each had its advantage. In facts, the reaction mechanism and luminescence properties play a decisive role in the biology application of H2S fluorescence probe. In this despite booming season, in the process of research we still skillfully conceived, in view of H2S with small structure being able to do successive nucleophilic substitution in the same molecules, high selective H2S subcellular detection was realized. Specifically, we take the cyanine (Cy7) with positive charge as a red fluorophore, through the introduction of disulfide bond and carbonate to build the specific reaction sites of H2S, thus avoiding the interference of other sulfur-containing substances in biological systems. After reaction with H2S, the Probe released red fluorophore, realizing mitochondria target H2S detection. Because the advantages of red fluorescence emission probe, the Probe successfully was applied imaging in mice.

Nanoenvironmental Effects Dramatically Influence the Sensitivity of Immunoassays

It is possible to improve the sensitivity of immunoassays by several orders of magnitude by exploiting nanoenvironmental effects. This approach can detect trace amounts of compounds and will better illuminate the presence of signal substances in biological systems. Here we describe a method for ultrasensitive immunoassays using 'normal' antibodies (Abs).

Comparative safety evaluation of silica-based particles

PurposeSilica nanoparticles (SNPs) are increasingly used as drug delivery systems (DDS) and for biomedical imaging. Therapeutic and diagnostic agents can be incorporated into the silica matrix to improve the stability and dissolution of drug substances in biological systems. However, the safety of SNPs as drug carriers remains controversial. To date, no validated and accepted nano-specific tests exist to predict the potentially harmful impact of these materials on the human body. MethodsWe synthesized by a systematic approach 12 different types of SNPs with varying size, surface topology (porous vs non-porous), and surface modifications. We characterized these particles in terms of dry state and hydrodynamic diameter, specific surface area, and net surface charge (ζ-potential). For cellular studies, we exposed non-phagocytic (HepG2) cells, phagocytic (THP-1) cells, and erythrocytes to SNPs. Cellular uptake and stability of fluorescently labeled SNPs were analyzed by confocal microscopy and flow cytometry. ResultsSNPs with a porous surface and negative net surface charge had the strongest impact on cell viability. This is in contrast to non-porous SNPs. None of the studied particles induced oxidative stress in either cell lines. Particles with a negative surface charge induced hemolysis in a concentration-dependent manner. ConclusionsPhysico-chemical properties promoting cytotoxicity and hemolysis were investigated. Our study revealed potential hazards of spherical amorphous SNPs.

The thermodynamic theory of evolution and aging

Life in the Universe emerges and develops under certain conditions in accordance with the general laws of nature, in particular, in accordance with the law of temporal hierarchies, the second law of thermodynamics and the principle of stability of matter. Biological evolution and organism's aging are accompanied by a change in the chemical and supramolecular compositions of living bodies. As shown by the author in 1977 these well-known changes have the thermodynamic nature (origin). Phenomenological hierarchical thermodynamics of near-equilibrium quasi-closed systems allows us to explain and predict the evolutionary transformation in the living world. From a viewpoint of power-consuming substance of biological objects the phenomenon of life, first, is the struggle for power-consuming chemicals. The accumulation of this substance in biological systems is associated with the aspiration of the specific Gibbs function of formation of supramolecular structures of living organisms to a minimum. The development of classical science opens up new horizons to explore the real world and contributes to the success of gerontology and geriatrics. This paper is a brief review containing new results.

Zinc-controlled gene expression by metal-regulatory transcription factor 1 (MTF1) in a model vertebrate, the zebrafish

There is a growing appreciation for the diverse roles of zinc as a signalling substance in biological systems. Zinc signalling is brought about by changes in intracellular concentrations of labile Zn(2+), resulting in both genomic and non-genomic effects. The genomic responses are largely mediated by MTF1 (metal-regulatory transcription factor 1), which binds to MREs (metal-response elements) in the 5' regulatory region of genes in response to zinc. Treatment of cultured zebrafish ZF4 cells with siRNA (small interfering RNA) to MTF1 changed the transcriptional response to zinc for over 1000 genes, as assessed using an oligonucleotide microarray. From this primary list of MTF1-dependent genes, we identified a relatively small cohort that showed a configuration of MREs in their 5' regulatory regions similar to known MTF1 targets. This group showed a remarkable dominance of nucleic acid-binding proteins and other proteins involved in embryological development, implicating MTF1 as a master regulator of gene expression during development.

The principle of parametric fractionation (separation) of substances in biological systems and technology

The parametric fractionation (separation) of substances is based on simultaneous exposure of a heterogeneous system with the phases (solid and liquid or liquid and gaseous) including components subject to be separated to the influence of two periodic fields of different nature. One field, “parameter” (for instance, temperature, pH) causes periodical redistribution of the components between phases, and the other field (for instance, mechanical forces, surface tension, electric field) effects synchronous shift of the components of one phase with respect to the other. As a result a counter flow of components to be separated formed against the gradient of their chemical or electrochemical potentials. This method underlain by the general principle of synchronous detection by no means is connected with definite mixtures or sorbents, it operates spontaneously in the inanimate and animate natural systems and can be applied to quite unexpected technologies.

Crystal Structure and Liquid Crystalline State of Cholesteryl Butylcarbonate

The crystal crystal structures of a series of esters and carbonates of cholesterol was examined, in order to obtain structural information relevant to their liquid crystalline phases and the possible modes of association of the cholesterol derivatives, as well as of other substances in biological systems. An examination of the unit-cell parameters of the cholesterol derivatives suggests that the majority of them might have one of the four common crystal packing arrangements. However, the crystal data of the cholesteryl butylcarbonate obtained in this study indicate that this carbonate belongs to none of these four crystal structure types. Cholesteryl butylcarbonate crystallized into two polymorphic forms, both of which exhibited liquid crystalline states. By carrying out the crystal structure determination of cholesteryl butylcarbonate, we have provided information on which to base extrapolations concerning the structures of the liquid phases of cholesteryl butylcarbonate.

Isomorphic Crystal Structures of Two Cholesterol Ethers

A series of crystal structures of the ethers, esters and carbonates of cholesterol were examined to obtain the structural information relevant to the liquid crystalline phases and the possible modes of association between the cholesterol derivatives and themselves as well as with other substances in biological systems. An examination of the unit cell parameters of the cholesterol derivatives suggests that the majority of the derivatives might have one of three common crystal packing arrangements, so called monolayer type I, type II and bilayer. The crystal data of cholesteryl ethylether and isopropylether obtained in this study indicate that those ethers belong to monolayer type II. Therefore, the primary aim of this study is to obtain the structural information on the conformation and the mode of the molecular interactions. The bond lengths and angles of cholesteryl ethylether and isopropylether are in good agreement, within experimental error, with those found in other cholesterol derivatives (see Table 1). The bond lengths in the C17 tails and ether chains show the apparent shortening which is characteristic of cholesterol derivatives, and is caused by the high thermal vibrations in these regions. In this case, it is especially pronounced in the C25-C27, C28-C29 and C28-C30 bond distances. The values of the atomic thermal parameters are unusually large, particularly in the ether groups and the terminal isopropyl group, C25, C26 and C27. The atoms, C3, O3, C28 and C29 lie in the same plane, with the torsion angle about O3-C28 being 176.0 (5)° for ethylether and 175.6(9)° for isopropylether, respectively. The isoprenoid chain at C17 is almost fully extended. The seven atoms of C17, C20, C22-C26 are in a zigzag planar chain and C21 and C27 are out of the plane. The crystal structures of cholesteryl ethylether and cholesteryl isopropyl ether (Fig. 2) consists of antiparallel molecules arranged to form monolayers which are parallel to the crystal (001) planes. Such monolayers are called type II. The monolayers are regions of closely packed semi-rigid cholesteryl ring systems that are separated by interface regions where the ether group atoms are more loosely packed. This packing type is similar to those of cholesteryl hexanoate, heptanoate, octanoate, pentyl carbonate, hexyl carbonate, oleate and chloroformate. The difference in the monolayer thickness (11.10-18.76 A) is associated primarily with structural differences in the interface region. The atoms in this region consist of the ester, carbonate or ether attached to O3 of cholesterol molecules. Most of the layered structures show liquid crystalline states, but these were not observed in the crystals of cholesteryl isopropylether. Crystals of cholesteryl isopropylether melt to give an isotropic liquid at a high temperature, 131.4 C. On cooling the crystals, freezing occurs at a temperature (117.1 C) which is considerably lower than the melting point. In cholesteryl ethylether, melting occurs at 87.7 C. The cholesteric phase forms only on cooling (73.3 C). The freezing point of the cholesteryl ethylether is

Compartmental analysis of dielectric absorption in capacitors

This paper proposes a method of studying and modeling the dielectric absorption in capacitors. Because of dielectric absorption, the voltage on a charged capacitor partially recovers after momentarily shorting its terminals. The magnitude of this voltage recovery depends mainly on the dielectric material. Dielectric absorption causes errors in some analog applications based on charging and discharging of capacitors, such as sample-and-hold circuits, integrators and active filters. Designing compensation circuits based on models of the dielectric absorption can reduce these errors. This paper presents an analytical method to build a mathematical model of the dielectric absorption, and an equivalent electrical circuit. The method is based on compartmental analysis theory, mostly used in medicine and biology to study the kinetics of substances in biological systems.

Electronic Sensing of Tastes

The taste sensor showed a similar pattern for chemical substances producing the same taste qualities, while quite different patterns were obtained for substances with different taste qualities. In fact, similar outputs were obtained for, e.g., NaCl, KCl and KBr eliciting saltiness, whereas their patterns differed clearly from those for other basic taste qualities. The taste of amino acids was also classied into several groups in accordance with the human taste sense. The taste sensor has a new concept of global selectivity. What is important in recognition of taste is not discrimination of minute difference in molecules but to transform molecular information contained in interactions with biological membranes into several kinds of groups, i.e., taste intensities and qualities. This function is of a high level, where intelligent sensing is required. In this sense, the taste sensor is essentially an intelligent sensor to reproduce the taste sense, which is a complex, comprehensive sense of humans. Several kinds of commercial drinks such as coffee, beer and mineral water were discriminated easily using the taste sensor. The taste sensor has a sensitivity, reproducibility and durability higher than those of humans. Human taste expressions such as ‘bitterness’ and ‘sourness’ were quantied, and also the physico-chemical indices for food production such as alcohol concentration and titratable acidity were shown to be measured by the taste sensor. Improvements in the membranes and measurement methods have also been made for the purpose of measurements, e.g., by adopting the Langmuir�Blodgett method [38], a monolayer of thiol-containing lipids [39] or impedance measurements [40]. The taste sensor will be applicable for quality control in the food industry and will help the automation of production. The sense of taste is vague and largely depends on subjective factors of human feelings. If we compare the standard index measured by means of the taste sensor with sensory evaluation, we will be able to assess taste objectively. Moreover, the mechanism of information processing of taste in the brain as well as the reception at taste cells will also be claried by developing a taste sensor which has output similar to that of the biological gustatory system. In fact, a recent study [19] has shown that astringency is a taste expressed by bitterness and sourness, whereas astringency has so far been considered not as a taste sense but a tactile sense. The result using the taste sensor indicates that the reception mechanism of taste substances in biological systems should be reconsidered. Objective scales of physical quantities such as length and time were proposed over two thousand years ago. We are now familiar with quantitative, objective scales, although there exists subjective feeling as well. As for taste, however, we have had no scale so far. The taste sensor provides a quantitative, objective measure of taste. ‘Deliciousness’ will be measured simultaneously using other sensors. Excellent odor or gas sensing systems based on various principles have also been developed [41—47]. We are now standing on the threshold of a new age of food culture.

Assessment of data sets containing a considerable number of values below the detection limits.

Using real examples it is demonstrated that the concentrations of non-essential substances in biological systems always follow a statistical log-normal distribution. This is based on the assumption that in a first-order approximation the rate of excretion of the quantity of unwanted molecules or atoms in the biological system is only dependent on their concentration. Applying a natural logarithmic transformation, the resulting log-normal distribution always has a standard deviation of about 1, as shown by statistical analysis of more than 680 clusters of analytical results. Assuming a log-normal distribution with a standard deviation of 1, it is possible to derive factors for the estimation of percentiles, such as the median, even when this percentile is below the detection limit; quantifiable and higher percentiles only must be multiplied by a specific factor. This new method has the advantage that no arbitrary assumptions must be made about artificial parameters such as the numerical treatment of non-detectable analytical data. The assumptions used for the calculation of the factors are justified by proof with experimental data. The applicability of the new method is demonstrated for various contaminants in various plants and animals.

In vitro adsorption losses of arachidonic acid and calcium ionophore A23187

Arachidonic acid (AA) is often utilized in in vitro studies to label cellular pools of AA or to elicit cellular responses dependent on eicosanoid production. Because of the hydrophobic nature of AA, organic diluents such as ethanol or dimethyl sulfoxide are utilized in preparing concentrated solutions. The fate of AA when added to aqueous medium is not generally considered because of the dilution of the AA, although some investigators utilize bovine serum albumin (BSA) to solubilize as well as to trap AA and its hydrophobic metabolites. These experiments demonstrate a rapid and progressive decline in AA concentration when added to aqueous media in tissue baths and in glass test tubes. The extent of the decline was greater in the tissue baths than in the test tubes. The calcium ionophore A23187, which is used to stimulate AA metabolism, is also hydrophobic, and its concentration also decreased when added to aqueous media. The decline in the concentration of both AA and A23187 was due to adsorption to the container walls. The presence of 1% BSA in the aqueous solution attenuated and even eliminated the decline in the concentration, indicating binding of the two agents to the protein. However, the presence of BSA in culture medium inhibited the A23187-induced stimulation of AA metabolites in baboon aortic smooth muscle cells. These results underscore the complexities arising from the in vitro use of hydrophobic substances in biological systems.

Leukemia and the reducing property of viruses.

Investigations of native blood of healthy people and of patients with acute leukemia have shown that the disease might be caused by a strongly reducing substance, which is presumably a virus. Evidence for this conclusion was obtained mainly by electron spin resonance (ESR) studies and by the determination of the catalase activity. ESR spectra of leukemic blood revealed an additional signal not present in spectra of healthy blood. Investigation of different blood fractions has shown that this signal is caused by a species present in the leukocytes only. Addition of reduced glutathione to healthy blood immediately after blood drawing resulted in the same signal. On the contrary, oxidizing substances, such as oxidized glutathione and KMnO4, added to the blood of leukemic patients immediately after its drawing, caused a disappearance of this signal depending on the concentration. Since the strongly reducing substances causes a reduction in the concentration of the oxidizing substances in biological systems, the H2O2 levels should be also affected and, thus, the catalase activity, too. As expected, the activity of this enzyme in the leukemic blood seems to be considerably lower than in healthy blood.

Concepts, properties, measurement, and computation of clearance rates of hormones and other substances in biological systems

A unified view of “clearance rates” for hormones and other substances in biological systems is developed and the overall concept is analyzed in the context of practical measurement schemes and the insights such measures can provide about a system. Several important properties and limitations of clearance rates, including plasma and “metabolic” clearance rates, are developed and analyzed. Among several new definitions presented, a new name, weighted-average plasma clearance rate (WAPCR), is suggested for a traditional measure of the plasma (or metabolic) clearance rate, i.e., the “dose divided by integral of the concentration” measure. This is done because the latter quantity represents a “plasma clearance rate” easy to interpret and apply only under special circumstances. It is shown that practical use of this so-called “model-independent” measure to determine the PCR is limited by the dynamical properties of the physiological system and experiment as well as the model chosen to represent it in the calculation. These situations, as well as other experiment design problems, are made explicit and their limitations are analyzed.

On the sensitivity of the methane fermentation of calcium acetate towards some toxic substances.

1. Methane fermentation of Ca-acetate is about as sensitive to phenylhydrazine, hydroxylamine and azide as it is to sulphite (inhibition by 10−2 m 70, 83, 94 and 95 % resp.; by 10−3 m 0, 39, 49 and 31 % resp.). 2. The sensitivity to dimedone is much less, 10−2 m inhibiting 17% only. 3. The process is much more sensitive to cyanide, 5.10−4 m giving already ±90% inhibition. 4. The sensitivity to sulphide is much less, as 5.10−2 m is necessary for complete inhibition, whereas 10−2 m does not inhibit at all. 5. Cultures of methane bacteria on Ca-acetate can be accustomed to 0.15 % formaldehyde which is fermented to CH4 and CO2 in presumably equimolecular proportions. 6. The results are discussed in the light of data on the action of these toxic substances in biological systems in general, with special reference to anaerobic bacteria.