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Effects of ethanol, acetaldehyde and disulfiram on the metabolism of biogenic aldehydes in isolated human blood cells and platelets.

The effects of ethanol, acetaldehyde and disulfiram on the metabolism of biogenic aldehydes were measured in different human blood fractions. Intact erythrocytes, leukocytes and platelets were incubated in phosphate-buffered saline with 3,4-dihydroxyphenylacetaldehyde (DOPAL) or 5-hydroxy-indole-3-acetaldehyde (5-HIAL), the aldehydes derived from dopamine and serotonin, respectively. The disappearance of the aldehyde and the formation of acid and alcohol metabolites were analysed in the presence of different concentrations of ethanol, acetaldehyde or disulfiram using high-performance liquid chromatography with electrochemical detection. Ethanol at a concentration of 20 mM did not affect the biogenic aldehyde metabolism. High concentrations of acetaldehyde caused a dose-dependent inhibition of the disappearance rate of the biogenic aldehydes and of the formation rate of acid metabolites. In incubations with leukocytes or platelets, the inhibition of the acid formation was associated with a slight increase in the formation of the alcohol metabolites. Disulfiram at a concentration of 50 microM totally inhibited the metabolism of DOPAL and 5-HIAL in incubations with erythrocytes or platelets, whereas much less inhibition was observed in incubations with leukocytes.

3,4-Dihydroxyphenylacetic Acid↗

The relationship between metal ion levels and biogenic amine levels in epileptic mice.

The metabolism of various metal ions and biogenic amines in El mice, an inbred mutant strain susceptible to epilepsy, was investigated as a possible model for seizure mechanism. Serum Na, P, Ca, Mg, Fe and Zn levels in El mice were lower than those in ddY mice, the mother strain of El mice. Conversely, bone Ca, P, Na, Mg and Zn levels in El mice were higher than those in ddY mice. The results obtained by chemical analysis are consistent with radiographic observations. Possible mechanisms for the lower serum metal ion levels seen in El mice include a decrease in availability of these ions from bone. The dopamine (DA) level in El mouse brain was 15% lower than in ddY mice but could be raised by intraventricular administration of CaCl2. This result was supported a decreased ethanol-induced sleeping time in El as compared to ddY mice, with 'normalization' occurring after intraventricular administration of Da or CaCl2. The biogenic amine levels disorder in El mice is discussed on the basis of our pharmacological observation that biogenic amine synthesis is regulated by divalent cations via a calmodulin-dependent system. Our results suggest that the disorders of metal ion metabolism could be a mechanism for epileptic convulsions in El mice.

Animals↗

Microspectrofluorometry in biogenic amine research.

Microspectrofluorometry has played an important part in the development and understanding of fluorescence techniques for the demonstration of biogenic amines. This paper reviews briefly the techniques currently available for the characterization and localization of biogenic amines, and considers the basic design considerations applicable to the construction of a microspectrofluorometer, with special emphasis on the automated correction of spectral data. Spectral data for the commonly occurring biogenic amines dopamine, noradrenaline and 5-hydroxytryptamine have been summarized and the criteria applicable to the spectral analysis of the individual amines and their mixtures discussed. Discrepancies between spectral data derived from tissues and model systems are reviewed and emphasis is given to the importance of biochemical studies of amines prior to definitive microspectrofluorometric analysis. The conceptual basis of quantitative microspectrofluorometry is reviewed with a particular emphasis on the limitations of such studies. The analysis of terminal fields by scanning microspectrofluorometry and its application to the study of extracellular amine distribution is discussed.

Animals↗

Anisotropic lattice distortions in biogenic calcite induced by intra-crystalline organic molecules.

We have performed precise structural measurements on five different calcitic seashells by high-resolution X-ray powder diffraction on a synchrotron beam line and by laboratory single crystal X-ray diffraction. The unit cell parameters a and c of biogenic calcite were found to be systematically larger than those measured in the non-biogenic calcite. The maximum lattice distortion (about 2.10(-3)) was detected along the c-axis. Under heat treatment above 200 degrees C, a pronounced lattice relaxation was observed, which allowed us to conclude that anisotropic lattice swelling in biogenic calcite is induced by organic macromolecules incorporated within the single crystal calcitic prisms during biomineralization. This conclusion is supported by the results of crystallization experiments in the presence of specific protein extracted from one of the shells.

Animals↗

Biogenic arsenopyrite in holocene peat sediment, India.

The plant organic matter in the peat layer deposited around 6650+/-110 and 4800+/-80 years BP, during the transgressive and regressive phases of sea level changes, respectively in the dried part (playa) of the present Pulicat lagoon in Palar Basin (southeast coast of India) was studied to elucidate the biogenic pyrite generation and associated trace elements. The scanning electron microscopic (SEM) observations show strongly curved unique C-shaped bacteria of uniform coccoidal shape and size (1 microm) freely scattered on the plant epidermal microfragments. These form spheroidal microcolonies 8-15 microm in diameter attached to the epidermis in a linear fashion or haphazardly enclosed in the translucent sheath as observed in surface view. These colonies are dense with a number of toxic trace elements as analyzed under an SEM-EDX spectrometer indicating its affinity toward metal binding. On maturity the sheath ruptures disseminating tetrad form of bacteria along with some C-shaped bacteria and few rhombohedral crystals of framboidal pyrite. The pyrite crystals intact in spheroidal shape in cavities on the epidermal fragments indicate its biogenic precipitation mediated by the bacteria. The pyrite crystals are rich in sulfur, iron, and traces of arsenic when analyzed by the SEM-EDX spectrometer. It is suggested that cubic and pyritohedran forms of crystals are perhaps arsenopyrite precipitated biogenically in saturated coastal wetland ecosystem in the past mediated by tetrad strain of the observed coccoid bacteria. Thus, the strata-bound peat layer could be the potent residing place for arsenopyrite or other toxic trace elements that may contaminate the groundwater aquifer.

Arsenicals↗

Raman spectroscopy study of the interaction between biogenic polyamines and an alternating AT oligodeoxyribonucleotide.

The interaction between the 15-mer oligonucleotide d[A(TA)(7)].d[T(AT)(7)] and the three biogenic polyamines, putrescine, spermidine and spermine, under physiological conditions has been studied by Raman spectroscopy. Solutions containing 60 mM (phosphate) of the oligonucleotide and different polyamine concentrations ranging from 1 to 75 mM have been studied. Both natural and heavy water were used as solvents. Difference Raman spectra were computed by subtracting the sum of the separated component spectra from the experimental spectra of the complexes. The Raman data suggested that the interaction of biogenic polyamines with d[A(TA)(7)].d[T(AT)(7)] presents differences related with their sizes and electric charges. Preferential bindings through the oligonucleotide minor groove for putrescine and spermidine were proposed. Spermine would interact by both minor and major grooves, although interaction by the minor groove seems to be more favored. Main reactive sites were thymine-O2 and adenine-N3 atoms at the minor grooves and adenine-N7 and thymine-O4 at the major groove. Electrostatic attractions between the polyamine amino and oligonucleotide phosphodioxy groups were also proposed. Under our experimental conditions, no macromolecular effects on d[A(TA)(7)].d[T(AT)(7)] (changes on secondary or tertiary structures) were detected from Raman spectroscopy, contrary to what happened for GC sequences at the same experimental settings. This fact agrees with the role of the biogenic polyamines during the first steps of the macromolecular synthesis, which involve DNA opening in AT motifs.

Adenosine↗

New views of biogenic amine transporter function: implications for neuropsychopharmacology.

Biogenic amine transporters, namely the dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (serotonin, 5-HT) transporters (DAT, NET and 5-HTT, respectively) appear to be the key elements in regulating biogenic amine neurotransmission. These proteins therefore represent a primary target for therapeutic intervention in the treatment of numerous psychiatric disorders, such as depression, anxiety and perhaps even schizophrenia as well as drug abuse. The cloning of DAT, NET and 5-HTT and development of selective radioligands for them over the last decade has dramatically increased our understanding of their location, structure and function. These breakthroughs have also enabled remarkable progress in determining how biogenic amine transporters are regulated under not only normal conditions but also when confronted with acute or chronic exposure to a variety of stimuli including psychotherapeutic drugs. Because of the important therapeutic consequences of a better understanding of these transporters, the present review discusses recent advances in defining their mechanism of action, location and regulation and the implications of the newer data for neuropsychopharmacology.

Journal Article↗

On-line solid-phase extraction with surfactant accelerated on-column derivatization and micellar liquid chromatographic separation as a tool for the determination of biogenic amines in various food substrates.

A sensitive method was developed for the determination of biogenic amines at very low levels by combining solid phase extraction (SPE) and derivatization on-line with HPLC. The on-line derivatization and SPE were performed simultaneously on a commercially available ODS guard column, which was installed instead of the filling loop on the HPLC apparatus. Resolution of the peaks and quantification was further enhanced with micellar liquid chromatography and sensitization of the benzene ring absorption at 254 nm. Detection limits of the benzoyl derivatives of biogenic amines were in the vicinity of 0.1 microg L(-)(1), which is even lower than those obtained by fluorescence detection and is unparallel to any other UV approach. The correlation coefficients of determinations were 0.9850-0.9998. The method was applied to the determination of Biogenic amines, that is, putrescine, cadaverine, agmatine, tyramine, tryptamine, phenylethylamine, spermine, spermidine and histamine in fish, chicken, and wine samples. Recovery of the proposed method ranged from 94 to 106%.

Amines↗

A new test procedure for biogenic sulfuric acid corrosion of concrete

A new test method is described for biogenic sulfuric acid corrosion of concrete, more specifically in sewer conditions. The aim of the new test method is the development of an accelerated and reproducible procedure for monitoring the resistance of different types of concrete with regard to biogenic sulfuric acid corrosion. This experimental procedure reflects worst case conditions by providing besides H2S, also an enrichment of thiobacilli and biologically produced sulfur. By simulating the cyclic processes occurring in sewer pipes, significant differences between concrete mixtures could be detected after 51 days. Concrete modified by a styrene-acrylic ester polymer demonstrated a higher resistance against biogenic sulfuric acid attack.

Journal Article↗

Biogenic amine production by Lactobacillus.

AIMS: The aim of this work was to demonstrate that strains of Lactobacillus may be able to produce putrescine and agmatine from one of the major amino acids present in fruit juices and wine, arginine, and from amino acid-derived ornithine. METHODS AND RESULTS: Biogenic amines were determined by HPLC. Their production in the culture medium was similar under both microaerophilic and anaerobic conditions. The presence of Mn2+ had a minimal influence on the results, whereas the addition of pyridoxal phosphate increased amine production 10-fold. Lactobacillus hilgardii X1B, isolated from wine, was able to degrade arginine by two pathways: arginine deiminase and arginine decarboxylase. The isolate was able to produce putrescine from ornithine and from agmatine. Lactobacillus plantarum strains N4 and N8, isolated from orange, utilized arginine via the arginine deiminase system. Only the N4 strain was able to produce putrescine from ornithine. CONCLUSION: It has been demonstrated that Lact. hilgardii X1B is able to produce the most important biogenic amine found in wine, putrescine, and also agmatine from arginine and ornithine, and that Lactobacillus plantarum, considered to be an innocuous spoilage micro-organism in fruit juices, is able to produce amines. SIGNIFICANCE AND IMPACT OF THE STUDY: The results have significance in relation to food poisoning caused by beverages that have been contaminated with biogenic amines.

Agmatine↗

Rett syndrome: stimulation of endogenous biogenic amines.

Transient hypercapnic hyperoxemia was induced in two Rett syndrome children by the administration of a gaseous mixture of 80% O2 and 20% CO2. Time course studies of neurotransmitters and their metabolites showed an immediate and marked increase in central biogenic amine turnover following inhalation of the gas mixture. The increased turnover of biogenic amines was associated with improved clinical changes. This suggests a coupled relationship and provides further support for an etiological role of neurotransmitter dysfunction in Rett syndrome. In a complementary study, elevation of pulmonary CO2 by application of a simple rebreathing device resulted in improvement of abnormal blood gases and elimination of the Cheyne-Stokes-like respiratory pattern of the Rett syndrome. Near normalization of the EEG occurred when a normal respiratory pattern was imposed by means of a respirator. Taken together, these results lead to the preliminary conclusion that cerebral hypoxemia secondary to abnormal respiratory function may contribute to diminished production of biogenic amines in Rett syndrome.

Brain↗

Ebony, a novel nonribosomal peptide synthetase for beta-alanine conjugation with biogenic amines in Drosophila.

Using Ebony protein either expressed in Escherichia coli or in Schneider S2 cells, we provide evidence for its substrate specificity and reaction mechanism. Ebony activates beta-alanine to aminoacyladenylate by an adenylation domain and covalently attaches it as a thioester to a thiolation domain in a nonribosomal peptide synthetase (NRPS) related mechanism. In a second reaction, biogenic amines act as external nucleophiles on beta-alanyl-S-pantetheine-Ebony, thereby releasing in a fast reaction the dipeptide (peptidoamine) in a process that is novel in higher eucaryotes. Therefore, we define Ebony as a beta-alanyl-biogenic amine synthetase. Insight into the reaction mechanism stems from mutational analysis of an invariant serine that disclosed Ebony as a multienzyme with functional analogy to the starting modules of NRPSs. In light of a putative biogenic amine-deactivating capacity, Ebony function in the nervous system must be reconsidered. We propose that in the Drosophila eye Ebony is involved in the transmission process by inactivation of histamine through beta-alanyl conjugation.

Alanine↗

Biogenic amines modulate olfactory receptor neurons firing activity in Mamestra brassicae.

The modulatory effects of the biogenic amines octopamine and serotonin on pheromonal receptor neurons of Mamestra brassicae were investigated. The responses to sex pheromone components of two cells types (A and B) in single male long sensilla trichodea were monitored. Cell types A and B do not respond to the same compound. The response of type A to a pulse of the major sex pheromone component increased 5 min after octopamine injection. Responses of type B to other odorants increased after 30 min. In the absence of any pheromone stimulation the background firing activity of type A increased following octopamine injection. This background activity was used to evaluate the kinetics of octopamine and other biogenic amine effects on olfactory receptor neurons. Octopamine increased this background activity in a concentration- and time-dependent manner. Clonidine, an octopamine agonist, was shown to be more powerful in increasing the background activity of olfactory receptor neurons. The effects of octopamine and clonidine were hypothesized to arise from specific receptor activation as chlorpromazine (an octopamine antagonist) was shown to block the effect of octopamine. Serotonin, a known neuromodulator in most animal species, induced a reversible inhibition of spike firing. Altogether, these results indicate that biogenic amines can modulate the sensitivity of olfactory receptor neurons of moths either directly or by an action on adaptation.

Amines↗

N1-acetyl-N2-formyl-5-methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant.

The biogenic amine The biogenic amine N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) was investigated for its potential antioxidative capacity. AFMK is a metabolite generated through either an enzymatic or a chemical reaction pathway from melatonin. The physiological function of AFMK remains unknown. To our knowledge, this report is the first to document the potent antioxidant action of this biogenic amine. Cyclic voltammetry (CV) shows that AFMK donates two electrons at potentials of 456 mV and 668 mV, and therefore it functions as a reductive force. This function contrasts with all other physiological antioxidants that donate a single electron only when they neutralize free radicals. AFMK reduced 8-hydroxydeoxyguanosine formation induced by the incubation of DNA with oxidants significantly. Lipid peroxidation resulting from free radical damage to rat liver homogenates was also prevented by the addition of AFMK. The inhibitory effects of AFMK on both DNA and lipid damage appear to be dose-response related. In cell culture, AFMK efficiently reduced hippocampal neuronal death induced by either hydrogen peroxide, glutamate, or amyloid b25-35 peptide. AFMK is a naturally occurring molecule with potent free radical scavenging capacity (donating two electrons/molecule) and thus may be a valuable new antioxidant for preventing and treating free radical-related disorders.

8-Hydroxy-2'-Deoxyguanosine↗

Biogenic amines metabolism and blood chemistry of psychiatric patients.

The metabolism of biogenic amines and blood chemistry of psychiatric patients were investigated. Eighty newly admitted psychiatric patients suffering from schizophrenia, hypomania, mania and paranoid disorder, and matched with fifteen normal subjects were used for the study. Blood was collected and centrifuged, after which serum was extracted. Serum concentrations of biogenic amines, namely epinephrine, norepinephrine, dopamine and serotonin were determined using spectrofluorimetric method. Serum concentration of 5-HIAA, activities of alanine transaminase and aspartate transaminase were determined. The concentrations of serum protein, albumin, Na+, K+, Cl- and CO2 in the psychiatric patients and control subjects were determined using Synchron CX5 automated spectrophotometer. Results of the study showed that the concentrations of serum epinephrine and norepinephrine in the psychiatric patients were significantly increased, while the concentrations of dopamine and serotonin were significantly decreased, as compared with the controls. Serum 5-HIAA levels were significantly elevated in all psychiatric patients compared with the controls. There was a marked elevation of the activities of alanine transaminase and aspartate transaminase in all psychiatric syndromes, with the exception of paranoid disorder, which was reduced. Data of the study indicate that metabolism of biogenic amines and concentrations of serum proteins, enzymes and some electrolytes were significantly affected in psychiatric patients suffering form schizophrenia, hypomania, mania and paranoid disorder.

Adult↗

BIO-1211 (Biogen).

Biogen, in collaboration with Merck & Co, is developing late activator VLA-4 (alpha4beta1) integrin antagonists for the potential treatment of inflammatory conditions [271194]. Merck has begun phase II trials with the lead compound, BIO-1211, for asthma, Biogen is still conducting preclinical research for its designated indications [317648,319225]. Under the collaborative agreement, each company has worldwide rights to certain indications; Merck has rights for asthma and Biogen retains the rights to a number of smaller indications, including multiple sclerosis, inflammatory bowel disease, renal indications and most diseases in which the US patient population is less than 200,000 [271194]. VLA-4 inhibitors show anti-inflammatory action by inhibition of binding between adhesion factors and leukocytes, but with no loss of basophil function, and they have the advantage of specificity not seen with existing drugs [273417]. In February 1999, Lehman Brothers predicted 40% probabilities that the compound would reach the US and ex-US markets for the asthma indication (Merck), and launch onto these markets by 2003. Peak annual sales of US dollar 500 million (US) and US dollar 500 million (outside US) are predicted, both in 2010 [319225].

Journal Article↗

Vipoxin. A protein from Russell's viper venom with high affinity for biogenic amine receptors.

We have purified a small, basic protein with high affinity and selectivity for biogenic amine receptors to apparent homogeneity from the venom of Russell's viper (Vipera russelli). This protein, which we designate "vipoxin," has Mr = 13,000, and appears to exist in solution as a single polypeptide chain. It may contain 2 atypical amino acids. Vipoxin inhibits in a dose-dependent manner the binding of 3H-ligands to biogenic amine receptors, with apparent Ki values of 3 nM at alpha 1-adrenergic receptors, 5 nM at alpha 2-adrenergic receptors, 15 nM at dopamine receptors, and 32 nM at serotonin receptors. At concentrations up to 1 microM, vipoxin is inactive at beta-adrenergic, histamine, nicotinic cholinergic, muscarinic cholinergic, adenosine, gamma-aminobutyric acid, benzodiazepine, or opiate receptor binding sites. The effect of vipoxin is essentially irreversible over 20 h at alpha 1- and alpha 2-adrenergic receptors and serotonin receptors and is only slightly reversible at dopamine receptors. Norepinephrine protects alpha-adrenergic receptors from inhibition by vipoxin, while dopamine does not. Vipoxin has no protease activity but does have phospholipase A2 activity, which cannot account for its action on receptors, since receptor binding is assayed in the presence of 1 mM CoSO4 which completely and selectively inhibits the phospholipase activity. Other phospholipases A2 in the same venom lack vipoxin's action on receptors. In physiologic experiments, vipoxin behaves as an agonist at alpha 2-adrenergic receptors in the rat vas deferens and is over an order of magnitude more potent than norepinephrine itself. At alpha 1-adrenergic receptors, it is neither a simple agonist nor an antagonist, but selectively potentiates norepinephrine. Vipoxin may be a useful tool for biogenic amine receptor characterization.

Amino Acids↗

Role of some biogenic amines in the pathomechanism of glomerulonephritis. I. Histological examinations of kidneys in acute and chronic serum sickness in rabbits.

Investigations were carried out on the role of biogenic amines in the development of glomerulonephritis in rabbits using the experimental model of acute and chronic serum sickness. The animals immunized with foreign-species albumin received additionally 5HT and some of them were given reserpine or PCPA for reducing the level of biogenic amines. The results of histological examinations demonstrated a clear cut inhibitory effect of PCPA and reserpine on the development of inflammatory changes in the glomeruli, and their intensification with simultaneous 5HT administration. The obtained results seem to suggest a significant role of biogenic amines in the pathogenesis of inflammatory lesions developing in renal glomeruli in acute or chronic serum sickness in rabbits.

Acute Disease↗