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The presence of biogenic amines (BAs) in seafood can pose a health risk to consumers, as they have been linked to adverse reactions such as histamine poisoning. Although the only biogenic amine for which maximum limits have been set is histamine, it is also important to regulate the presence of other amines associated with certain adverse effects. In this study, the official method for determining histamine was slightly modified and adapted for a UHPLC-PDA system and applied to analyze raw and preserved mackerel fillet samples. The evolution of biogenic amines during the storage period under refrigerated conditions revealed that, within two days, the limit for the content of histidine of 100 mg/kg was exceeded in raw fillets, while the histidine content in preserved mackerel (in oil and marinated) remained more stable. The thawing phase, whether in the fridge or at room temperature, did not significantly affect the BA content. Additionally, three different cooking methods (steaming, oven-baking, and boiling) significantly decrease the levels of BAs in highly contaminated raw mackerel fillets.

Recently, prokaryotic laccases from lactic acid bacteria (LAB), which can degrade biogenic amines, were discovered. A laccase enzyme has been cloned from Oenococcus oeni, a very important LAB in winemaking, and it has been expressed in Escherichia coli. This enzyme has similar characteristics to those previously isolated from LAB as the ability to oxidize canonical substrates such as 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,6-dimethoxyphenol (2,6-DMP), and potassium ferrocyanide K4[Fe(CN6)], and non-conventional substrates as biogenic amines. However, it presents some distinctiveness, the most characteristic being its psychrophilic behaviour, not seen before among these enzymes. Psychrophilic enzymes capable of efficient catalysis at low temperatures are of great interest due to their potential applications in various biotechnological processes. In this study, we report the discovery and characterization of a new psychrophilic laccase, a multicopper oxidase (MCO), from the bacterium Oenococcus oeni. The psychrophilic laccase gene, designated as LcOe 229, was identified through the genomic analysis of O. oeni, a Gram-positive bacterium commonly found in wine fermentation. The gene was successfully cloned and heterologously expressed in Escherichia coli, and the recombinant enzyme was purified to homogeneity. Biochemical characterization of the psychrophilic laccase revealed its optimal activity at low temperatures, with a peak at 10 °C. To our knowledge, this is the lowest optimum temperature described so far for laccases. Furthermore, the psychrophilic laccase demonstrated remarkable stability and activity at low pH (optimum pH 2.5 for ABTS), suggesting its potential for diverse biotechnological applications. The kinetic properties of LcOe 229 were determined, revealing a high catalytic efficiency (kcat/Km) for several substrates at low temperatures. This exceptional cold adaptation of LcOe 229 indicates its potential as a biocatalyst in cold environments or applications requiring low-temperature processes. The crystal structure of the psychrophilic laccase was determined using X-ray crystallography demonstrating structural features similar to other LAB laccases, such as an extended N-terminal and an extended C-terminal end, with the latter containing a disulphide bond. Also, the structure shows two Met residues at the entrance of the T1Cu site, common in LAB laccases, which we suggest could be involved in substrate binding, thus expanding the substrate-binding pocket for laccases. A structural comparison of LcOe 229 with Antarctic laccases has not revealed specific features assigned to cold-active laccases versus mesophilic. Thus, further investigation of this psychrophilic laccase and its engineering could lead to enhanced cold-active enzymes with improved properties for future biotechnological applications. Overall, the discovery of this novel psychrophilic laccase from O. oeni expands our understanding of cold-adapted enzymes and presents new opportunities for their industrial applications in cold environments.

Tyramine (TRM) is a biogenic catecholamine neurotransmitter, which can trigger migraines and hypertension. TRM accumulated in foods is reduced and detected using additive cyclodextrins (CDs) while their association characteristics remain unclear. Here, single-crystal X-ray diffraction and density functional theory (DFT) calculation have been performed, demonstrating the elusive pseudopolymorphs in β-CD inclusion complexes with TRM base/HCl, β-CD·0.5TRM·7.6H2O (1) and β-CD·TRM HCl·4H2O (2) and the rare α-CD·0.5(TRM HCl)·10H2O (3) exclusion complex. Both 1 and 2 share the common inclusion mode with similar TRM structures in the round and elliptical β-CD cavities, belong to the monoclinic space group P21, and have similar herringbone packing structures. Furthermore, 3 differs from 2, as the smaller twofold symmetry-related, round α-CD prefers an exclusion complex with the twofold disordered TRM–H+ sites. In the orthorhombic P21212 lattice, α-CDs are packed in a channel-type structure, where the column-like cavity is occupied by disordered water sites. DFT results indicate that β-CD remains elliptical to suitably accommodate TRM, yielding an energetically favorable inclusion complex, which is significantly contributed by the β-CD deformation, and the inclusion complex of α-CD with the TRM aminoethyl side chain is also energetically favorable compared to the exclusion mode. This study suggests the CD implications for food safety and drug/bioactive formulation and delivery.

Foodborne contaminants such as biogenic amines (BAs), nitrite and sulfite are harmful to human health. To safeguard food safety, the content of BAs, nitrite and sulfite should be strictly controlled. Small-molecule fluorescent probes are a promising analytical tool for monitoring BAs, nitrite and sulfite because they are highly sensitive and selective, offer simplicity of operation, and can enable optical signal visualization of the analyte. In this review, we summarize the most recent progress on the development of fluorescent probes for selectively detecting BAs, nitrite, and sulfite. In particular, we discuss the working mechanisms, sensing performance, and practical applications of various fluorescent probes that have been developed in recent years for detecting BAs, nitrite, and sulfite, with a particular emphasis on the utilization of these probes in food. Lastly, we discuss the research directions, trends, and prospects of molecular fluorescent probes in food applications in the future. We hope this review can offer conceptual and design guidance for researchers and practitioners to develop novel fluorescent probes for food safety.

Volatile organic amines and biogenic amines produced by the amino acid degradation can undeniably affect the food quality and safety, and thus causes serious health problems. It is of great urgency to exploit reliable and sensitive detection methods for amines to ensure food safety and public health. The fluorescent and colorimetric sensors offer simple and robust means to monitor amines with high sensitivity and selectivity, quick response, facile operation and low cost. Herein, we briefly review the past five years’ progress in fluorescent and colorimetric sensing for monitoring organic and biogenic amines in food. The architectures of sensing materials ranging from small molecules to frameworks to polymers or self-assembly materials have been highlighted. Moreover, the main challenges and perspective of various sensing materials are presented to inspire further research and development. In the end, the development trend of new sensing materials and devices for real-time monitoring of food quality is also forecasted. This review is expected spur more research interest in design of novel amine sensing materials for future application transformation research.

Sideritis scardica Griseb. and Clinopodium vulgare L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of S. scardica are well documented, the cognitive benefits of C. vulgare remain unexplored. This study assessed the potential effect of C. vulgare on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of S. scardica. Over a 21-day period, rats orally received extracts of cultivated S. scardica (200 mg/kg) and C. vulgare (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. S. scardica excelled in preserving spatial working memory, while C. vulgare exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development.

The development of food packaging materials that reduce the production of plastic, preserving at the same time the quality of food, is a topic of great interest today for the scientific community. Therefore, this article aims to report the effectiveness of an eco-friendly packaging material based on alginic acid and grape pomace extract from Vitis vinifera L. (winemaking by-products) for storing red meat in a domestic refrigerator. Specifically, biogenic amines are considered “sentinels” of the putrefactive processes, and their presence was thus monitored. For this purpose, an experimental analytical protocol based on the use of solid-phase microextraction coupled with gas chromatography–mass spectrometry was developed during this work for the determination of six biogenic amines (butylamine, cadaverine, isobutylamine, isopentylamine, putrescine, and tyramine). Moreover, by combining the analytical results with those of pH and weight loss measurements, differential scanning calorimetry, and microbiological analysis, it was proved that the studied materials could be proposed as an alternative packaging material for storing foods of animal origin, thus lowering the environmental impact according to sustainability principles.

This study aimed to investigate the influence of various production stages on the quality and spoilage conditions of traditionally dry-cured chorizo. To accomplish this, we employed an experimental design that examined three key production parameters: the batch, the filling stage, and the food smoking process. The study was conducted in collaboration with a local producer who adheres to traditional curing methods utilizing oak wood smoke and heat. Biogenic amine levels were closely monitored throughout the process. This involved their extraction and derivatization through the salting-out technique, followed by identification and quantification using LC-ESI/MSn and HPLC-DAD, respectively. The findings suggest that both raw materials and the production process are well controlled during the filling stage. However, it became evident that the 14-day oak wood smoking period had a significant impact on biogenic amine formation, whose total mean values increased from 126 to 1385 mg kg−1, particularly with respect to putrescine (PUT), cadaverine (CAD), and tyramine (TYR), although these levels remained below the oral toxicity limit (2000 mg kg−1). Consequently, the concentration of these compounds can influence the quality and safety of traditionally dry-cured chorizos. Therefore, the combined levels of PUT, CAD, and TYR can serve as a valuable quality indicator for these products.

Biogenic amines (BAs) are biologically active substances found in the cells of microorganisms, plants, and animals. These BAs serve many vital functions in the body. However, an excessive amount can be toxic, especially for individuals taking monoamine oxidase (MAO) and diamine oxidase (DAO) inhibitors. They primarily form in products rich in amino acids, the primary substrates for BA formation. The aim of this study was to determine the formation of BAs and their precursor amino acids in chicken breast and leg muscles stored under chilling conditions. Analyses of BA and AA determinations were conducted on days 1, 3, 5, 7, and 10 of muscle storage. There was a noted increase in BAs with the storage of both muscle types (p < 0.05). Distinct levels of BAs were detected (p < 0.05) in the muscles, except for putrescine (p > 0.05). Interactions emerged between the two factors for various Bas, including histamine (p = 0.001), tyramine (p < 0.001), BAI index (p < 0.001), tryptamine (p < 0.001), agmatine (p = 0.001), spermidine (p < 0.001), TOTAL BA-1 (p < 0.001), and TOTAL BA-2 (p = 0.016). There was no evident interaction between the type of meat and storage time concerning amino acid content (p > 0.05). Correlations in breast muscles were observed for biogenic amine–amino acid pairs such as putrescine–ornithine (r = −0.57) (p < 0.05), spermidine–ornithine (r = −0.73) (p < 0.05), and phenylethylamine–phenylethylalanine (r = −0.50) (p < 0.05). In leg muscles, significant correlations were found for histamine–histidine (r = −0.87) (p < 0.05), putrescine–ornithine (r = −0.96) (p < 0.05), and phenylethylamine–phenylethylalanine (r = −0.65) (p < 0.05). The results obtained can be used in the future to estimate the levels of BAs with knowledge of the levels of individual amino acids and inversely.

Objectives. Biogenic polyamines are widely present in nature. They are characteristic of both protozoan cells and multicellular organisms. These compounds have a wide range of biological functions and are necessary for normal growth and development of cells. Violation of polyamine homeostasis can cause significant abnormalities in cell functioning, provoking various pathological processes, including oncological and neuropsychiatric diseases. The impact on the “polyamine pathway” is an attractive basis for the creation of many pharmacological agents with a diverse spectrum of action. The purpose of this review is to summarize the results of the studies devoted to understanding the biological activity of compounds of the polyamine series, comparing their biological action with action on certain molecular targets. Due to the structural diversity of this group of substances, it is impossible to fully reflect the currently available data in one review. Therefore, in this work, the main attention is paid to the derivatives, acyclic saturated polyamines.Results. The following aspects are considered: biological functionality, biosynthesis and catabolism, cell transport, and localization of biogenic polyamines in the living systems. Structural analogs and derivatives of biogenic polyamines with antitumor, neuroprotective, antiarrhythmic, antiparasitic, antibacterial, and other biological activities are represented; the relationship between biological activity and the target of exposure is reflected. It was found that the nature of the substituent, the number of cationic centers, and the length of the polyamine chain have a great influence on the nature of the effect.Conclusions. At present, the use of polyamine structures is restrained by cytotoxicity and nonspecific toxic effects on the central nervous system. Further research in the field of biochemistry, cell transport, and a deeper understanding of receptor interaction mechanisms will help making polyamines as the basis for potential drug formulation.

This study demonstrates the effects of the freezing and frozen storage of anchovies prior to brining and dry-salting on quality changes and food safety during refrigerated storage (4 ± 1 °C). Fresh anchovies were divided into two groups, one of which was used as a control representing fresh raw material; the other was the experimental group and consisted of frozen and thawed anchovies stored at −18 °C for a year. Five different salt concentrations were used for brining (10, 15, 20, 25 and 30%) in addition to the dry-salting method. Microbiological, chemical, physical and sensory analyses were carried out during storage. Salt concentration and salting method had significant effects on the shelf-life of salted anchovy products, with the highest shelf-life corresponding to dry-salted anchovies (p < 0.05). The effect of using frozen and thawed raw materials for salting on the shelf-life depended on the processing method since the experimental dry-salted group had a shelf-life one month longer than that of the control group, while the opposite situation occurred for the brined samples, with one exception. Strong correlations were usually found between sensory values and chemical quality parameters (R2: 0.83–0.99 for the control group and 0.63–0.99 for the experimental group). The results demonstrated that the experimental group, with some exceptions, had better values for most quality and food safety parameters in comparison to the control group, indicating the advantage of using frozen and thawed raw materials before salting to prevent spoilage and enhance food safety. Considering that the experimental group was produced from one-year-stored raw material compared to the control group, the advantage of the freezing and frozen storage of anchovies can be accepted as much higher versus when freezing is not implemented. The positive effect is due to the fact that frozen anchovies absorb salt faster after thawing, especially in groups with high salt concentrations. Therefore, it can be concluded that frozen salted anchovies can be utilized for longer as they have a longer shelf-life, particularly when using either the 30% brining or dry-salting method.

The biogenic amines (BAs) synephrine (SNP), phenylephrine (PEP), tyramine (TYR), and octopamine (OCT) may be present in products widely consumed for weight loss, muscle power, and in energy supplements. Considering the toxicity of these BAs at high levels and their biomarker role in some human pathologies, their monitoring in urine can be of great help in the detection of abusive consumption or disease. In this work, a combination of dispersive liquid–liquid microextraction (DLLME) with ultra-high performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) for the simultaneous determination of four aromatic BAs in human urine is presented. The sample treatment included a previous derivatization step with dansyl chloride to achieve the highest extraction efficiency in the DLLME procedure for which a mixture of 350 μL of chloroform and 2 mL of ethanol was added to 5 mL of derivatized urine. Limits of detection were in the 0.54–3.6 µg L−1 range. Method precision and trueness were estimated at two concentration levels and were in the 3.4–10.2% and 93.6–114% ranges, respectively. The analysis of nine urine samples showed concentration levels for TYR between 52 and 304 µg L−1. Non-targeted analysis of the samples was undertaken to control the presence of other BAs and related metabolites, and none of these species was detected.

Biogenic amines (BAs) play an important role in the aggressive behavior of crustaceans. In mammals and birds, 5-HT and its receptor genes (5-HTRs) are characterized as essential regulators involved in neural signaling pathways during aggressive behavior. However, only one 5-HTR transcript has been reported in crabs. In this study, the full-length cDNA of the 5-HTR1 gene, named Sp5-HTR1, was first isolated from the muscle of the mud crab Scylla paramamosain using the reverse-transcription polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends (RACE) methods. The transcript encoded a peptide of 587 amino acid residues with a molecular mass of 63.36 kDa. Western blot results indicate that the 5-HTR1 protein was expressed at the highest level in the thoracic ganglion. Furthermore, the results of quantitative real-time PCR show that the expression levels of Sp5-HTR1 in the ganglion at 0.5, 1, 2, and 4 h after 5-HT injection were significantly upregulated compared with the control group (p < 0.05). Meanwhile, the behavioral changes in 5-HT-injected crabs were analyzed with EthoVision. After 0.5 h of injection, the speed and movement distance of the crab, the duration of aggressive behavior, and the intensity of aggressiveness in the low-5-HT-concentration injection group were significantly higher than those in the saline-injection and control groups (p < 0.05). In this study, we found that the Sp5-HTR1 gene plays a role in the regulation of aggressive behavior by BAs, including 5-HT in the mud crab. The results provide reference data for the analysis of the genetic mechanism of aggressive behaviors in crabs.

Mollusks comprise one of the largest phylum of marine invertebrates. With their great diversity of species, various degrees of mobility, and specific behavioral strategies, they haveoccupied marine, freshwater, and terrestrial habitats and play key roles in many ecosystems. This success is explained by their exceptional ability to tolerate a wide range of environmental stresses, such as hypoxia. Most marine bivalvemollusksare exposed to frequent short-term variations in oxygen levels in their marine or estuarine habitats. This stressfactor has caused them to develop a wide variety of adaptive strategies during their evolution, enabling to mobilize rapidly a set of behavioral, physiological, biochemical, and molecular defenses that re-establishing oxygen homeostasis. The neuroendocrine system and its related signaling systems play crucial roles in the regulation of various physiological and behavioral processes in mollusks and, hence, can affect hypoxiatolerance. Little effort has been made to identify the neurotransmitters and genes involved in oxygen homeostasis regulation, and the molecular basis of the differences in the regulatory mechanisms of hypoxia resistance in hypoxia-tolerant and hypoxia-sensitive bivalve species. Here, we summarize current knowledge about the involvement of the neuroendocrine system in the hypoxia stress response, and the possible contributions of various signaling molecules to this process. We thusprovide a basis for understanding the molecular mechanisms underlying hypoxic stress in bivalves, also making comparisons with data from related studies on other species.

The composition of the aqueous humor of patients with type 2 diabetes is relevant to understanding the underlying causes of eye-related comorbidities. Information on the composition of aqueous humor in healthy subjects is limited due to the lack of adequate controls. To carry out a metabolomics study, 31 samples of aqueous humor from healthy subjects without ocular pathology, submitted to refractive surgery and seven samples from patients with type 2 diabetes without signs of ocular pathology related to diabetes were used. The level of 25 molecules was significantly (p < 0.001) altered in the aqueous humor of the patient group. The concentration of a single molecule, N-acetylornithine, makes it possible to discriminate between control and diabetes (sensitivity and specificity equal to 1). In addition, receptor operating characteristic curve and principal component analysis for the above-mentioned six molecules yielded significantly (p < 0.001) altered in the aqueous humor of the patient group. In addition, receptor operating characteristic curve and principal component analysis for six compounds yielded cut-off values and remarkable sensitivity, specificity, and segregation ability. The altered level of N-acetylornithine may be due to an increased amount of acetate in diabetes. It is of interest to further investigate whether this alteration is related to the pathogenesis of the disease. The increase in the amino form of pyruvate, alanine, in diabetes is also relevant because it could be a means of reducing the formation of lactate from pyruvate.

The aim of the study was to assess the content of biogenic amines and physical properties of fruiting bodies of white and brown button mushrooms subjected to the process of controlled lactic acid fermentation. Lactiplantibacillus plantarum 299v with documented probiotic properties and L. plantarum EK3, i.e., an isolate obtained from spontaneously fermented button mushrooms, were used as starter strains. Fresh, blanched, fermented, and refrigerated fruiting bodies were analysed. The mushroom samples were found to contain three amines: spermidine, putrescine, and tyramine in amounts that do not pose a threat to consumer health. The highest content of spermidine was found in the fruiting bodies of unprocessed brown and white mushrooms (367.22 ± 14.19 and 266.47 ± 13.38 mg/kg, respectively). Putrescine and tyramine were found only in the fermented mushrooms. Putrescine ranged from 0.58 ± 0.25 to 10.11 ± 0.5 mg/kg, while tyramine ranged from 1.44 ± 0.25 to 69.04 ± 1.39 mg/kg. Histamine, which is the most toxic biogenic amine, was not detected in any of the samples. The technological process caused substantial changes in all colour parameters. The blanching process resulted in a decrease in the value of parameter L* and an increase in the value of parameters a* and b*. The process of lactic acid fermentation increased the brightness parameter. It also caused a substantial increase in the yellowness parameter and reduced the redness of the fermented mushrooms. Blanching exerted a significant effect on the texture of the mushroom fruiting bodies, contributing to an increase in the puncture force value from 2.78 ± 0.22 to 4.90 ± 0.43 N and from 3.21 ± 0.23 to 5.59 ± 0.3 N in the case of the white and brown mushrooms, respectively. During the refrigerated storage, the firmness of the fermented mushrooms did not change.

The studies concern the effect of the addition of acid whey in combination with sodium ascorbate on selected parameters related to proteolysis in uncured dry-fermented sausages. Four sausage samples (with different additives: curing mixture (C); sea salt (S); sea salt and liquid acid whey (SAW); sea salt, liquid acid whey and sodium ascorbate (SAWA)) were taken at day 0, 7, 14 and 21 of ripening to assess basic physicochemical properties, thiobarbituric acid-reactive substances (TBARS), peptides content, antioxidant properties and biogenic amines content. It was indicated that the addition the acid whey caused greater acidification of fermented sausages during processing and significantly lower level of biogenic amines and lipid oxidation. At 21 days, the pH and water activity of sausages ranged from 4.74 ± 0.01 to 5.04 ± 0.04 and from 0.868 ± 0.002 to 0.875 ± 0.003, respectively. The synergistic effect of whey and sodium ascorbate was particularly noticeable in the reduction of lipid oxidation products and antioxidant activity of peptides. The results showed a beneficial effect of the addition of acid whey in combination with sodium ascorbate on the quality features of fermented sausage.

This study aimed to assess the safety characteristics of organic high-protein bars (HPB) during storage at ambient and refrigerated temperatures based on selected microbiological and chemical indicators. After production, the total number of microorganisms ranged from 3.90–4.26 log CFU/g;. The Enterobacteriaceae family was present at 2.81–3.32 log CFU/g, and the count of yeasts and moulds was 2.61–3.99 log CFU/g. No Salmonella sp. was found in 25 g of the product. Bacillus cereus was present in samples B1 and B2. Staphylococcus aureus was presented in samples below the detection limit (B. cereus and other low water activity (aw) resistant microorganisms.

The GTP-binding protein-coupled receptors (GPCRs) play important roles in physiology and neuronal signaling. More than a thousand genes, excluding the olfactory receptors, have been identified that encode these integral membrane proteins. Their pharmacological and functional properties make them fascinating targets for drug development, since various disease states can be treated and overcome by pharmacologically addressing these receptors and/or their downstream interacting partners. The activation of the GPCRs typically causes transient changes in the intracellular second messenger concentrations as well as in membrane conductance. In contrast to ion channel-mediated electrical signaling which results in spontaneous cellular responses, the GPCR-mediated metabotropic signals operate at a different time scale. Here we have studied the kinetics of two common GPCR-induced signaling pathways: (a) Ca2+ release from intracellular stores and (b) cyclic adenosine monophosphate (cAMP) production. The latter was monitored via the activation of cyclic nucleotide-gated (CNG) ion channels causing Ca2+ influx into the cell. Genetically modified and stably transfected cell lines were established and used in stopped-flow experiments to uncover the individual steps of the reaction cascades. Using two homologous biogenic amine receptors, either coupling to Go/q or Gs proteins, allowed us to determine the time between receptor activation and signal output. With ~350 ms, the release of Ca2+ from intracellular stores was much faster than cAMP-mediated Ca2+ entry through CNG channels (~6 s). The measurements with caged compounds suggest that this difference is due to turnover numbers of the GPCR downstream effectors rather than the different reaction cascades, per se.

Highly electrosensitive platforms have been developed using different nanocomposite materials based on carbon allotropes and different metallic nanoparticles for determination of nitrite and biogenic amines (BAs). The nitrification process occurred in soil represents an important source of pollution. The nitrification consists in biological oxidation of the relatively immobile ammonium (NH4+) to highly mobile nitrate, via nitrite. This process is carried out mainly by the ammonia–oxidizing bacteria (Nitrosomonas sp. and Nitrobacter sp.) present in the soil microbial population [1,2]. The nitrite contamination of ground and surface waters represents the major concern associated with the nitrification process. Additionally, the growing needs for food and environmental safety has led to an increase in research for the detection of biogenic amines (BAs) in recent years. Despite the fact that BAs are increasingly present in food and beverages, causing toxic effects in the body, legislation that limits their presence in food chains needs to be updated, thus requiring sensitive tools for their detection [3,4]. Miniaturized analytical tools have been developed based on nanocomposite materials obtained through combination of different carbon allotrope materials (nanoribbons, nanotubes—single and multiwalled—and nanofibers) with metallic nanoparticles (Ag, Au-Ag, Pt, Cu). Thus, carbon based screen-printed electrodes (SPE) were chemically modified with the obtained nanocomposite materials and further characterized using different electrochemical techniques. In order to allow a selective and sensitive determination of analytes, an electropolymerized film was deposed on the modified sensors. For BAs determination were realized with two configurations of biosensors, a bienzymatic one consisting in immobilization of diamine oxidase (DAO) and horseradish peroxidase (HRP) onto the modified sensors, and, respectively, a mono-enzymatic system based on immobilization of DAO onto the modified sensors. It was taken into account that the charge of carbon-based nanomaterials on the surface of the sensors should not exceed 5%, in order to ensure a low based current. Morpho-structural and electrochemical characterization studies of the modified SPEs have been performed in order to achieve a high sensitivity and selectivity of detection, applying a low overvoltage. The co-polymeric film ensured a better stability of the nanocomposite material layers at the electrode surface and an optimal matrix for enzymes immobilization. Optimization of the nanocomposite-based sensors were performed, and finally detection of biogenic amines was carried out using biosensors based on single-walled carbon nanotubes and Pt nanoparticles, while nitrite determination was performed using multi-walled carbon nanotubes and AgNP modified sensors at applied potentials between −0.45 and +0.6 V vs. Ag/AgCL. The developed sensors and biosensors showed good sensitivities of nitrite and BAs detection. Although the enzyme DAO has a low enough activity to catalyze the oxidation of amine of interest, the detection limits were lowered due to the electrocatalytic activity of nanocomposite materials and the HRP enzyme used.

The nervous system expresses neuromolecules that play a crucial role in regulating physiological processes. Neuromolecule synthesis can be regulated by oxygen-dependent enzymes. Bivalves are a convenient model for studying air exposure-induced hypoxia. Here, we studied the effects of hypoxia on the expression and dynamics of neurotransmitters, and on neurotransmitter enzyme distribution, in the central nervous system (CNS) of the scallop Azumapecten farreri. We analyzed the expression of the neurotransmitters FMRFamide and serotonin (5-HT) and the choline acetyltransferase (CHAT) and universal NO-synthase (uNOS) enzymes during air exposure-induced hypoxia. We found that, in early-stage hypoxia, total serotonin content decreased in some CNS regions but increased in others. CHAT-lir cell numbers increased in all ganglia after hypoxia; CHAT probably appears de novo in accessory ganglia. Short-term hypoxia caused increased uNOS-lir cell numbers, while long-term exposure led to a reduction in their number. Thus, hypoxia weakly influences the number of FMRFamide-lir neurons in the visceral ganglion and does not affect peptide expression in the pedal ganglion. Ultimately, we found that the localization and level of synthesis of neuromolecules, and the numbers of cells expressing these molecules, vary in the scallop CNS during hypoxia exposure. This indicates their possible involvement in hypoxia resistance mechanisms.

Biogenic amines constitute an important group of neuroactive substances that control and modulate various neural circuits. These small organic compounds engage members of the guanine nucleotide-binding protein coupled receptor (GPCR) superfamily to evoke specific cellular responses. In addition to dopamine- and 5-hydroxytryptamine (serotonin) receptors, arthropods express receptors that are activated exclusively by tyramine and octopamine. These phenolamines functionally substitute the noradrenergic system of vertebrates Octopamine receptors that are the focus of this study are classified as either α- or β-adrenergic-like. Knowledge on these receptors is scarce for the American cockroach (Periplaneta americana). So far, only an α–adrenergic-like octopamine receptor that primarily causes Ca2+ release from intracellular stores has been studied from the cockroach (PaOctα1R). Here we succeeded in cloning a gene from cockroach brain tissue that encodes a β-adrenergic-like receptor and leads to cAMP production upon activation. Notably, the receptor is 100-fold more selective for octopamine than for tyramine. A series of synthetic antagonists selectively block receptor activity with epinastine being the most potent. Bioinformatics allowed us to identify a total of 19 receptor sequences that build the framework of the biogenic amine receptor clade in the American cockroach. Phylogenetic analyses using these sequences and receptor sequences from model organisms showed that the newly cloned gene is an β2-adrenergic-like octopamine receptor. The functional characterization of PaOctβ2R and the bioinformatics data uncovered that the monoaminergic receptor family in the hemimetabolic P. americana is similarly complex as in holometabolic model insects like Drosophila melanogaster and the honeybee, Apis mellifera. Thus, investigating these receptors in detail may contribute to a better understanding of monoaminergic signaling in insect behavior and physiology.

An accurate and sensitive method for trace quantification of three biogenic amines in expired apple juice samples based on reversed-phase liquid chromatography (RP-HPLC) with UV-visible detection is described. Biogenic amines including cadaverine, histamine, and tyramine, were converted to their acetylacetone derivatives in water-methanol medium. The proposed method involves a pre-column derivatization of species followed by RP-HPLC separation with Thermo Hypersil Gold reversed-phase column and UV detection at 315 nm. A flow rate of 0.9 mL min-1 was used in the proposed method. An efficient separation of biogenic amines was successfully performed in 11 min with a good resolution using 35:65 % (v/v) acetonitrile-water mixture as the mobile phase. Detection limits of 0.03, 0.23, and 0.08 μg L-1 were obtained for cadaverine, histamine and tyramine, respectively. The proposed method has been successfully applied for the analysis of two different commercially available expired apple juice samples. Recovery rates between 98.78 and 102.12 % were obtained with an RSD of 0.16-1.65 % for the analysis of 20 mL of expired apple juice samples indicating that the recoveries of biogenic amines were very satisfactory.

Vaginal malodour is a sign of dysbiosis. The biogenic amines (BAs) cadaverine, putrescine and tyramine are known to be causative compounds. Recent reports suggest these compounds produced by pathogens might have a role beyond causing malodour; namely inhibiting the growth of lactobacilli bacteria that are crucial in the maintenance of vaginal homeostasis. The aim of this study was to identify whether certain lactobacilli strains could reduce BAs and to evaluate how Lactobacillus species were affected by these compounds. Using LC–MS and HPLC-UV, five Lactobacillus crispatus strains were identified as being capable of significantly reducing BAs from the media under in vitro conditions. Through 16S rRNA gene sequencing of vaginal swabs exposed to Bas, cadaverine was found to reduce the relative abundance of lactobacilli. When L. crispatus was exposed to media supplemented with BAs with an HCl adjusted lower pH, its growth was enhanced, demonstrating the relevance of the maintenance of an acidic vaginal environment. If strains are to be developed for probiotic application to alleviate bacterial vaginosis and other conditions affecting large numbers of women worldwide, their ability to adapt to Bas and regulate pH should be part of the experimentation.

Human monoamine transporters (MATs) are cation transporters critically involved in neuronal signal transmission. While inhibitors of MATs have been intensively studied, their substrate spectra have received far less attention. Polyspecific organic cation transporters (OCTs), predominantly known for their role in hepatic and renal drug elimination, are also expressed in the central nervous system and might modulate monoaminergic signaling. Using HEK293 cells overexpressing MATs or OCTs, we compared uptake of 48 compounds, mainly phenethylamine and tryptamine derivatives including matched molecular pairs, across noradrenaline, dopamine and serotonin transporters and OCTs (1, 2, and 3). Generally, MATs showed surprisingly high transport activities for numerous analogs of neurotransmitters, but their substrate spectra were limited by molar mass. Human OCT2 showed the broadest substrate spectrum, and also the highest overlap with MATs substrates. Comparative kinetic analyses revealed that the radiotracer meta-iodobenzylguanidine had the most balanced uptake across all six transporters. Matched molecular pair analyses comparing MAT and OCT uptake using the same methodology could provide a better understanding of structural determinants for high cell uptake by MATs or OCTs. The data may result in a better understanding of pharmacokinetics and toxicokinetics of small molecular organic cations and, possibly, in the development of more specific radiotracers for MATs.

The aim of the study is to compare the effects of Salvia hispanica (Chia) seed and Nigella sativa (Black Cumin) seed in traditionally produced dry fermented sausages with reduced nitrites on the changes in physicochemical parameters (water content, pH, and water activity), thioarbituric acid reactive substances (TBARS), color parameters, the content of nitrosopigments, and microbial counts throughout the production process. At the end of the processing, the content of biogenic amines was also determined. Five samples were analyzed during the 30-day production process: the control sample, samples with 1% and 2% additions of chia seed, and samples with 1% and 2% additions of black cumin seed. It was indicated that the addition of chia or black cumin did not exert any effect on water content or water activity changes in fermented sausages. At the end of production, the samples were characterized by low water activity, in the range of 0.798–0.813. The sausages with chia seeds were characterized by the lowest pH due to the highest proliferation of lactic acid bacteria. TBARS values did not alter in both control and black cumin sausages throughout the experiment. Microbiological analysis showed that the addition of chia or black cumin seed enhances the proliferation of the lactic acid bacteria and caused a reduction in the number of Enterobacteriaceae in comparison to the control.

The striatum plays a fundamental role in motor learning and reward-related behaviors that are synergistically shaped by populations of D1 dopamine receptor (D1R)- and D2 dopamine receptor (D2R)-expressing medium spiny neurons (MSNs). How various neurotransmitter inputs converging on common intracellular pathways are parsed out to regulate distinct behavioral outcomes in a neuron-specific manner is poorly understood. Here, we reveal that distinct contributions of D1R-MSNs and D2R-MSNs towards reward and motor behaviors are delineated by the multifaceted signaling protein neurofibromin 1 (NF1). Using genetic mouse models, we show that NF1 in D1R-MSN modulates opioid reward, whereas loss of NF1 in D2R-MSNs delays motor learning by impeding the formation and consolidation of repetitive motor sequences. We found that motor learning deficits upon NF1 loss were associated with the disruption in dopamine signaling to cAMP in D2R-MSN. Restoration of cAMP levels pharmacologically or chemogenetically rescued the motor learning deficits seen upon NF1 loss in D2R-MSN. Our findings illustrate that multiplex signaling capabilities of MSNs are deployed at the level of intracellular pathways to achieve cell-specific control over behavioral outcomes. [ABSTRACT FROM AUTHOR]

Happiness, or Subjective Well-Being (SWB), is generally considered as a peaceful and satisfied state accompanied by consistent and optimistic mood. Due to its subjective and elusive nature, however, wellbeing has only been scarcely investigated in the neuroimaging literature. In this study, we investigated its neural substrates by characterizing two different perspectives: self- or other-concerned wellbeing. In the present study, 22 participants evaluated the subjective happiness (with button presses 1 to 4) to 3 categories (intra- and inter-personal and neutral) of pre-rated pictures in a slow event-related fMRI. Because wellbeing is constantly featured by pleasure feelings after self-inspection, we predict that happier conditions, featured by “intra-personal vs. neutral” and “inter-personal vs. neutral” conditions, should yield higher BOLD activities in overlapping reward- and self-related regions. Indeed, medial prefrontal (mPFC), pregenual ACC (pACC), precuneus and posterior cingulate cortex (PCC) were revealed both by General Linear Model (GLM) (categorical contrasts) and parametric modulations (correlations with rating 1-4s), specifically, more connectivity between nucleus accumbens (NAcc) and mPFC, via additional psychophysiological interaction, or PPI, analyses. More interestingly, GLM and multivariate searchlight analyses jointly reveal the subdivision of mPFC and the PCC/precuneus, with anterior mPFC and dorsal PCC/precuneus more for interpersonal, posterior mPFC and ventral PCC/precuneus more for intrapersonal, SWB, respectively. Taken together, these results are not only consistent with the “cortical midline hypothesis of the self”, but also extending the “spatial gradients of self-to-other-concerned processing” from mPFC to including both mPFC and PCC/precuneus, making them two “hubs” of self-to-other-concerned wellbeing network. [ABSTRACT FROM AUTHOR]

Confined hydration and conformational flexibility are some of the challenges encountered for the rational design of selective antagonists of G-protein coupled receptors. We present a set of C3-substituted (-)-stepholidine derivatives as potent binders of the dopamine D3 receptor. The compounds are characterized biochemically, as well as by computer modeling using a novel molecular dynamics-based alchemical binding free energy approach which incorporates the effect of the displacement of enclosed water molecules from the binding site. The free energy of displacement of specific hydration sites is obtained using the Hydration Site Analysis method with explicit solvation. This work underscores the critical role of confined hydration and conformational reorganization in the molecular recognition mechanism of dopamine receptors and illustrates the potential of binding free energy models to represent these key phenomena. [ABSTRACT FROM AUTHOR]

The ventral midbrain supports a variety of functions through the heterogeneity of neurons. Dopaminergic and GABA neurons within this region are particularly susceptible targets of amphetamine-class psychostimulants such as methamphetamine. While this has been evidenced through single-neuron methods, it remains unclear whether and to what extent the local neuronal network is affected and if so, by which mechanisms. Both GABAergic and dopaminergic neurons were heavily featured within the primary ventral midbrain network model system. Using spontaneous calcium activity, our data suggest methamphetamine decreased total network output via a D2 receptor-dependent manner. Over culture duration, functional connectivity between neurons decreased significantly but was unaffected by methamphetamine. However, across culture duration, exposure to methamphetamine significantly altered changes in network assortativity. Here we have established primary ventral midbrain networks culture as a viable model system that reveals specific changes in network activity, connectivity, and topology modulation by methamphetamine. This network culture system enables control over the type and number of neurons that comprise a network and facilitates detection of emergent properties that arise from the specific organization. Thus, the multidimensional properties of methamphetamine can be unraveled, leading to a better understanding of its impact on the local network structure and function. [ABSTRACT FROM AUTHOR]

Gap junctions (GJs), which consist of proteins called connexins, are intercellular channels that allow the passage of ions, second messengers, and small molecules. GJs and connexins are considered as emerging therapeutic targets for various diseases. Previously, we screened numerous compounds using our recently developed iodide yellow fluorescent protein gap junctional intercellular communication (I-YFP GJIC) assay and found that flunarizine (FNZ), used for migraine prophylaxis and as an add-on therapy for epilepsy, inhibits GJIC in LN215 human glioma cells. In this study, we confirmed that FNZ inhibits GJIC using the I-YFP GJIC assay. We demonstrated that FNZ inhibits GJ activities via a mechanism that is independent of calcium channels and dopaminergic D2, histaminergic H1, or 5-HT receptors. In addition, we showed that FNZ significantly increases connexin 43 (Cx43) phosphorylation on the cell surface, but does not alter the total amount of Cx43. The beneficial effects of FNZ on migraines and epilepsy might be related to GJ inhibition. [ABSTRACT FROM AUTHOR]

Biochemical changes in utero may alter normal fetal development, resulting in disease later in life, a phenomenon known as fetal programming. Recent epidemiological studies link fetal programming to negative health outcomes, such as low birth weight and hypertension in adulthood. Here, we used a WKY rat model and studied the molecular changes triggered by prenatal glucocorticoid (GC) exposure on the development of hypertension, and on the regulation of phenylethanolamine N-methyl transferase (PNMT), the enzyme responsible for biosynthesis of epinephrine, and a candidate gene linked to hypertension. Clinically, high doses of the synthetic GC dexamethasone (DEX) are used to treat infant respiratory distress syndrome. Elevated maternal GCs have been correlated with fetal programming of hypertension. The aim of this study was to determine if lower doses of DEX would not lead to detrimental fetal programming effects such as hypertension. Our data suggests that prenatal stress programs for increased expression of PNMT and altered regulation of PNMT in males and females. Importantly, we identified that DEX mediated programming was more apparent in the male rats, and the lower dose 10μg/kg/day of DEX did not lead to changes in blood pressure (BP) in female rats suggesting that this dose is below the threshold for programming of hypertension. Furthermore, sex-specific differences were observed in regards to programming mechanisms that may account for hypertension in males. [ABSTRACT FROM AUTHOR]

Cell-to-cell communication is a key element of microvascular blood flow control, including rapidly carrying signals through the vascular endothelium in response to local stimuli. This cell-to-cell communication is negatively impacted during inflammation through the disruption of junctional integrity. Such disruption is associated with promoting the onset of cardiovascular diseases as a result of altered microvascular blood flow regulation. Therefore, understanding the mechanisms how inflammation drives microvascular dysfunction and compounds that mitigate such inflammation and dysfunction are of great interest for development. As such we aimed to investigate extracts of mushrooms as potential novel compounds. Using intravital microscopy, the medicinal mushroom, Inonotus obliquus was observed, to attenuate histamine-induced inflammation conducted vasodilation in second-order arterioles in the gluteus maximus muscle of C57BL/6 mice. Mast cell activation by C48/80 similarly disrupted endothelial junctions and conducted vasodilation but only histamine was blocked by the histamine antagonist, pyrilamine not C48/80 suggesting the importance of mast cell activation. Data presented here supports that histamine induced inflammation is a major disruptor of junctional integrity, and highlights the important anti-inflammatory properties of Inonotus obliquus focusing future assessment of mast cells as putative target for Inonotus obliquus. [ABSTRACT FROM AUTHOR]

Holometabolous insects stop feeding at the final larval instar stage and then undergo metamorphosis; however, the mechanism is unclear. In the present study, using the serious lepidopteran agricultural pest Helicoverpa armigera as a model, we revealed that 20-hydroxyecdysone (20E) binds to the dopamine receptor (DopEcR), a G protein-coupled receptor, to stop larval feeding and promote pupation. DopEcR was expressed in various tissues and its level increased during metamorphic molting under 20E regulation. The 20E titer was low during larval feeding stages and high during wandering stages. By contrast, the dopamine (DA) titer was high during larval feeding stages and low during the wandering stages. Injection of 20E or blocking dopamine receptors using the inhibitor flupentixol decreased larval food consumption and body weight. Knockdown of DopEcR repressed larval feeding, growth, and pupation. 20E, via DopEcR, promoted apoptosis; and DA, via DopEcR, induced cell proliferation. 20E opposed DA function by repressing DA-induced cell proliferation and AKT phosphorylation. 20E, via DopEcR, induced gene expression and a rapid increase in intracellular calcium ions and cAMP. 20E induced the interaction of DopEcR with G proteins αs and αq. 20E, via DopEcR, induced protein phosphorylation and binding of the EcRB1-USP1 transcription complex to the ecdysone response element. DopEcR could bind 20E inside the cell membrane or after being isolated from the cell membrane. Mutation of DopEcR decreased 20E binding levels and related cellular responses. 20E competed with DA to bind to DopEcR. The results of the present study suggested that 20E, via binding to DopEcR, arrests larval feeding and promotes pupation. [ABSTRACT FROM AUTHOR]

Human fumarylacetoacetate hydrolase (FAH) domain containing protein 1 (FAHD1) is a mitochondrial oxalocatate decarboxylase, the first of its kind identified in eukaryotes. The physiological role of FAHD1 in other eukaryotes is still poorly understood. In C. elegans loss of the FAHD1 ortholog FAHD-1 was reported to impair mitochondrial function, locomotion and egg-laying behavior, yet the underlying mechanisms remained unclear. Using tissue-specific rescue of fahd-1(-) worms, we find that these phenotypic abnormalities are at least in part due to fahd-1’s function in neurons. Moreover, we show that egg-laying defects in fahd-1(-) worms can be fully rescued by external dopamine administration and that depletion of fahd-1 expression induces expression of several enzymes involved in serotonin biosynthesis. Together, our results support a role for fahd-1 in modulating serotonin levels and suggest this protein as a novel link between metabolism and neurotransmitter signaling in the nervous system. Finally, we propose a model to explain how a metabolic defect could ultimately lead to marked changes in neuronal signaling. [ABSTRACT FROM AUTHOR]

The metacercariae of the Clonorchis sinensis liver fluke excyst in the duodenum of mammalian hosts, and the newly excysted juveniles (CsNEJs) migrate along the bile duct via bile chemotaxis. Cholic acid is a major component of bile that induces this migration. We investigated the neuronal control of chemotactic behavior of CsNEJs toward cholic acid. The migration of CsNEJs was strongly inhibited at sub-micromolar concentration by dopamine D1 (LE-300 and SKF-83566), D2 (spiramide, nemonapride, and sulpiride), and D3 (GR-103691 and NGB-2904) receptor antagonists, as well as a dopamine reuptake inhibitor (BTCP). Neuropeptides, FMRFamide, peptide YY, and neuropeptide Y were also potent inhibitors of chemotaxis. Meanwhile, serotonergic, glutamatergic, and cholinergic inhibitors did not affect chemotaxis, with the exception of fluoxetine and CNQX. Confocal immunofluorescence analysis indicated that dopaminergic and cholinergic neurons were colocalized in the somatic muscle tissues of adult C. sinensis. Our findings suggest that dopaminergic neurons and neuropeptides play a major role in the chemotactic migration of CsNEJs to bile, and their inhibitors or modulators could be utilized to prevent their migration from the bile duct. [ABSTRACT FROM AUTHOR]

We showed previously an epinephrine-induced inhibition of the Na+/K+ ATPase in Caco-2 cells mediated via PGE2. This work is an attempt to further elucidate mediators downstream of PGE2 and involved in the observed inhibitory effect. The activity of the Na+/K+ ATPase was assayed by measuring the amount of inorganic phosphate liberated in presence and absence of ouabain, a specific inhibitor of the enzyme. Changes in the protein expression of the Na+/K+ ATPase were investigated by western blot analysis which revealed a significant decrease in the abundance of the ATPase in plasma membranes. Treating the cells with epinephrine or PGE2 in presence of SC19220, a blocker of EP1 receptors abolished completely the effect of the hormone and the prostaglandin while the effect was maintained unaltered in presence of antagonists to all other receptors. Treatment with calphostin C, PTIO, ODQ or KT5823, respective inhibitors of PKC, NO, soluble guanylate cyclase and PKG, abrogated completely the effect of epinephrine and PGE2, suggesting an involvement of these mediators. A significant inhibition of the ATPase was observed when cells were treated with PMA, an activator of PKC or with 8-Br-cGMP, a cell permeable cGMP analogue. PMA did reduce the protein expression of IκB, as shown by western blot analysis, and its effect on the ATPase was not manifested in presence of an inhibitor of NF-κB while that of SNAP, a nitric oxide donor, was not affected. The results infer that NF-κB is downstream PKC and upstream NO. The data support a pathway in which epinephrine induces the production of PGE2 which binds to EP1 receptors and activates PKC and NF-κB leading to NO synthesis. The latter activates soluble guanylate cyclase resulting in cGMP production and activation of PKG which through direct or indirect phosphorylation inhibits the Na+/K+ ATPase by inducing its internalization. [ABSTRACT FROM AUTHOR]

Background: Many patients with major depressive disorder (MDD) fail to respond to antidepressant (AD) pharmacotherapy. The objectives of this study were to characterize MDD and treatment-resistant depression (TRD) at the level of pharmacologically treated episodes and to describe the sequential treatment patterns by lines of therapy (LOT) in the first two episodes. Methods: Adults (≥18 years of age) with continuous enrollment ≥12 months before and after the first MDD diagnosis and treated with an AD, with or without an MDD-indicated antipsychotic (AP), were identified (1/1/2010-12/31/2015). The MDD episode started on the date of MDD diagnosis that was preceded by a clean period without any MDD diagnosis. The MDD episode ended on the last MDD diagnosis or the end of the days’ supply of AD/AP medication, whichever came last. TRD was defined as an MDD episode with ≥3 AD/AP regimens. Measured outcomes included episode duration, number of LOT, relapse hospitalization, and sequential treatment patterns of MDD episode stratified by TRD and non-TRD episodes. Results: Of 48,440 patients who received AD/AP in the 1st MDD episode, 3,317 (6.8%) of episodes were considered TRD. Mean duration of 1st TRD episodes was 571 days, mean number of AD/AP LOTs was 3.47, and 13.7% involved relapse hospitalization. Mean duration of 1st non-TRD episodes was 200 days, mean number of AD/AP LOTs was 1.21, and 9.6% involved relapse hospitalization. Among 1st MDD episodes, 25.5% had a second LOT; 7.3% had a third LOT. Most patients received selective serotonin reuptake inhibitors (SSRIs) as the first LOT (63.0%), and the plurality of regimens were SSRIs in second (44.9%) and third LOT (41.1%). Conclusions: Compared to non-TRD episodes, TRD episodes were longer and more often involved relapse hospitalizations. SSRIs were the most common treatment; treatment changes and potential treatment unresponsiveness were frequent among MDD patients. [ABSTRACT FROM AUTHOR]

Mutations in ATP13A2 cause Kufor-Rakeb syndrome (KRS), a juvenile form of Parkinson’s disease (PD) with dementia. However, the mechanisms by which mutations in ATP13A2 cause KRS is not understood. The mutations lead to misfolding of the translated Atp13a2 protein and its premature degradation in the endoplasmic reticulum, never reaching the lysosome where the protein is thought to function. Atp13a2 is a P-type ATPase, a class of proteins that function in ion transport. Indeed, studies of human, mouse, and yeast Atp13a2 proteins suggest a possible involvement in regulation of heavy metal toxicity. Here we report on the cytoprotective function of Atp13a2 on HeLa cells and dopamine neurons of Caenorhabditis elegans (C. elegans). HeLa cells stably overexpressing V5- tagged Atp13a2Isoform-1 protein were more resistant to elevated manganese exposure and to starvation-induced cell death compared to cells not overexpressing the protein. Because PD is characterized by loss of dopamine neurons, we generated transgenic C. elegans expressing GFP-tagged human Atp13a2 protein in dopamine neurons. The transgenic animals exhibited higher resistance to dopamine neuron degeneration after acute exposure to manganese compared to nematodes that expressed GFP alone. The results suggest Atp13a2 Isoform-1 protein confers cytoprotection against toxic insults, including those that cause PD syndromes. [ABSTRACT FROM AUTHOR]

The neural mechanisms underlying behavioral therapy for vocal acoustic deficits in patients with Parkinson disease is unknown. A primary hypothesis is that voice therapy may modulate mesolimbic brainstem regions, including the ventral tegmental area (VTA). The VTA is implicated in ultrasonic call peak frequency, involved in rewarding behaviors, and impacted by Parkinsonism. We tested the hypothesis that chronic (daily) behavioral vocal exercise of male Pink1-/- rats would alter ultrasonic vocalization acoustics and mesolimbic neurochemistry (catecholamines, GABA, mu-opioid receptor) compared to three different controls: sham-exercised Pink1-/-, unexercised Pink1-/-, and unexercised wildtype (WT) rats. A sub-hypothesis is that sham-exercise rats may exhibit changes to VTA neurochemistry as a result of a type or rewarding intervention. Results demonstrate that average bandwidth (frequency range) of ultrasonic vocalizations did not differ between WT, Pink1-/- no exercise vs. sham and vocal-exercise rats. However, average peak frequency is significantly reduced in vocal-exercised Pink1-/- rats compared to Pink1-/- no exercise, and WT groups. Unexpectedly, there were no significant acoustic differences between the vocal- and sham-exercised groups. There were no differences in catecholamine protein concentrations or tyrosine hydroxylase mRNA expression in the VTA between any of the groups. However, there was significant upregulation of all GABA-related genes in both vocal- and sham-exercised Pink1-/- rats (Gad1, Gad2, Gls, Glul); this finding was confirmed with follow up quantitative Western blotting for GAD. Additionally, there were differential results for mu-opioid receptor quantification in the VTA: vocal-exercised Pink1-/- rats showed increased mRNA expression for mu-opioid receptors whereas Western blotting indicated decreased protein levels in all Pink1-/- rats compared to WT controls suggesting the possible onset of pathology in this model. These data demonstrate modulatory effects of a rewarding behavioral paradigm on ultrasonic vocalization peak frequency. The results suggest that neuromodulators such as GABA and opioid activity, as well as the rewarding aspects of therapy may play a key role in shaping vocal treatments. [ABSTRACT FROM AUTHOR]

Previous research has suggested an association between antidepressants use and clinical restless legs syndrome (RLS) in patients, but there has never been a single study investigating the risk of RLS in irritable bowel syndrome (IBS) patients treated with antidepressants. Hence, we aimed to explore the association between IBS and RLS and to examine the risk of RLS in IBS patients treated with antidepressants. With the use of the National Health Insurance Research Database of Taiwan, 27,437 adults aged ≥ 20 years with newly diagnosed IBS (ICD-9-CM Code 564.1) and gender- and age-matched 54,874 controls without IBS were enrolled between 2000 and 2012. All patients were followed-up until RLS diagnosis, withdrawal from the National Health Insurance program, or end of 2013. We used the Cox proportional hazards model to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of RLS. RLS was more prevalent in IBS patients than in the non-IBS group (7.57 versus 3.36 per 10,000 person-years), with an increased risk of RLS (adjusted HR [aHR], 1.91; 95% CI, 1.52–2.40). Multivariate Cox proportional hazards analysis identified older age (age, 51–65 years; aHR, 1.67; 95% CI, 1.09–2.56; and age > 65; aHR, 1.59; 95% CI, 1.02–2.48), hypothyroidism (aHR, 4.24; 95% CI, 1.92–9.37), CAD (aHR, 1.70; 95% CI, 1.17–2.48), and depression (aHR, 3.15; 95% CI, 2.14–4.64) as independent RLS risk factors in IBS patients. In addition, the male SSRIs users were associated with significantly higher risk of RLS (aHR, 3.05 95% CI, 1.34–6.92). Our study showed that the IBS group has higher risk of RLS. Moreover, SSRIs use may increase the risk of RLS in male IBS patients. [ABSTRACT FROM AUTHOR]

Background: Endotoxin induces an inflammatory response, with secondary release of cytokines, which can progress to shock and multiple organ failure. We explored whether continuous renal replacement therapy (CRRT) using a modified membrane (oXiris) capable of adsorption could reduce endotoxin and cytokine levels in septic patients. Methods: Sixteen patients requiring CRRT for septic shock-associated acute renal failure and who had endotoxin levels >0.03 EU/ml were prospectively randomized in a crossover double-blind design to receive CRRT with an oXiris filter or with a standard filter. Endotoxin and cytokine levels were measured at baseline and 1, 3, 8, 16 and 24 hours after the start of CRRT. Norepinephrine infusion rate and blood lactate levels were monitored. Results: During the first filter treatment period, endotoxin levels decreased in 7 of 9 (77.8%) oXiris filter patients, but in only 1 of 6 (16.7%) standard filter patients (P = 0.02). Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and interferon (IFN)γ decreased more with the oXiris filter than with the standard filter. Lactate concentration decreased with oXiris (-1.3[-2.2 to -1.1] mmol/l, P = 0.02), but not with the standard filter (+0.15[-0.95 to 0.6]). The norepinephrine infusion rate was reduced during oXiris CRRT, but not during standard filter CRRT. In the second filter treatment period, there was no significant reduction in endotoxin or cytokine levels in either group. Conclusions: CRRT with the oXiris filter seemed to allow effective removal of endotoxin and TNF-α, IL-6, IL-8 and IFNγ in patients with septic shock-associated acute renal failure. This may be associated with beneficial hemodynamic effects. [ABSTRACT FROM AUTHOR]

Handling and consumption of Campylobacter-contaminated poultry meat is the most common cause of human campylobacteriosis. While many studies deal with interventions to reduce Campylobacter spp. on chicken carcasses, studies on other poultry species are rare. In the present study, a spray treatment with peracetic acid (PAA) on turkey carcasses was evaluated. For this, parts of breast fillets with skin and Campylobacter (C.) jejuni DSM 4688 (108 cfu/ml) inoculated drumsticks were sprayed for 30 s with PAA (1200 ppm) or water as control solution. Samples were packaged under modified atmosphere and stored at 4°C until analysis on day 1, 6 and 12. The breast fillets were used for determination of the total viable count, sensory and meat quality examination as well as myoglobin content and biogenic amines. The drumsticks were used for C. jejuni counts. PAA had a significant effect in reducing total viable counts on all days by up to 1.2 log10 compared to the untreated control. Treatment with water alone showed no effect. C. jejuni counts were significantly reduced by PAA (0.9–1.3 log10), while water achieved a 0.5 log10 reduction on C. jejuni counts on day 1. No differences in sensory, pH, electrical conductivity and myoglobin content could be found. The skin of the PAA treated fillets had lower redness values than the water control on day 1, whereas on day 12 parts of the water treated muscles were lighter than the untreated control. A lower putrescine content of the water sprayed fillets in comparison to the control sample on day 12 was the only significant difference concerning the biogenic amines. Results from this study indicate that a spray treatment with 1200 ppm PAA would be a useful measure to lower the Campylobacter spp. counts on turkey carcasses without having a negative influence on product quality. [ABSTRACT FROM AUTHOR]