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17β-estradiol treatment has shown benefit against schizophrenia symptoms, however longterm use may be associated with negative side-effects. Selective estrogen receptor modulators, such as raloxifene and tamoxifen, have been proposed as suitable alternatives to 17β- estradiol. An isomer of 17β-estradiol, 17α-estradiol, is considered less carcinogenic, and non-feminising in males, however little is known about its potential as a treatment for schizophrenia. Moreover, the mechanism underlying the therapeutic action of estrogens remains unclear. We aimed to investigate the ability of these estrogenic compounds to attenuate psychosis-like behaviour in rats. We used two acute pharmacologically-induced assays of psychosis-like behaviour: psychotomimetic drug-induced hyperlocomotion and disruption of prepulse inhibition (PPI). Female Long Evans rats were either intact, ovariectomised (OVX), or OVX and chronically treated with 17β-estradiol, 17α-estradiol, raloxifene or tamoxifen. Only 17β-estradiol treatment attenuated locomotor hyperactivity induced by the indirect dopamine receptor agonist, methamphetamine. 17β-estradiol- and tamoxifen-treated rats showed attenuated methamphetamine- and apomorphine (dopamine D1/D2 receptor agonist)- induced disruption of PPI. Raloxifene-treated rats showed attenuated apomorphineinduced PPI disruption only. Baseline PPI was significantly reduced following OVX, and this deficit was reversed by all estrogenic compounds. Further, PPI in OVX rats was increased following administration of apomorphine. This study confirms a protective effect of 17β- estradiol in two established animal models of psychosis, while tamoxifen showed beneficial effects against PPI disruption. In contrast, 17α-estradiol and raloxifene showed little effect on dopamine receptor-mediated psychosis-like behaviours. This study highlights the utility of some estrogenic compounds to attenuate psychosis-like behaviour in rats, supporting the notion that estrogens have therapeutic potential for psychotic disorders.

BackgroundHepatocellular carcinoma (HCC) is rapidly increasing in the U.S. and is a leading cause of mortality for patients with cirrhosis. Discovering novel biomarkers for risk stratification of HCC is paramount. We examined biomarkers of the gut-liver axis in a prospective multicenter cohort.MethodsPatients with cirrhosis without a history of HCC were recruited between May 2015 and March 2020 and prospectively followed at 3 tertiary care hospitals in Los Angeles. Microbiome analysis was performed on duodenal biopsies and metabolomic analysis was performed on serum samples, collected at the time of enrollment. Optimal microbiome-based survival analysis and Cox proportional hazards regression analysis were used to determine microbiota and metabolite associations with HCC development, respectively.ResultsA total of 227 participants with liver cirrhosis contributed a total of 459.58 person-years of follow-up, with 14 incident HCC diagnoses. Male sex (HR = 7.06, 95% CI = 1.02-54.86) and baseline hepatic encephalopathy (HE, HR = 4.65, 95% CI = 1.60-13.52) were associated with developing HCC over follow-up. Adjusting for age, sex, baseline HE, and alkaline phosphatase, an increased risk of HCC were observed for participants with the highest versus lowest three quartiles for duodenal Alloprevotella (HR = 3.22, 95% CI = 1.06-9.73) and serum taurocholic acid (HR = 6.87, 95% CI = 2.32-20.27), methionine (HR = 9.97, 95% CI = 3.02-32.94), and methioninesulfoxide (HR = 5.60, 95% CI = 1.84-17.10). Being in the highest quartile for Alloprevotella or methionine had a sensitivity and specificity for developing HCC of 85.71% and 60.56%, respectively, with an odds ratio of 10.92 (95% CI = 2.23-53.48).ConclusionAlloprevotella and methionine, methioninesulfoxide, and taurocholic acid predicted future HCC development in a high-risk population of participants with liver cirrhosis.

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.

Background: COVID-19 can be related to any diseases caused by microbial infection(s) because 1) co-infection with COVID-19-related virus and other microorganism(s) and 2) because metabolites produced by microorganisms such as bacteria, fungi, and protozoan can be involved in necrotizing pneumonia and other necrotizing medical conditions observed in COVID-19. Objective: By way of illustration, the microbial metabolite of aromatic amino acid tryptophan, a biogenic amine tryptamine inducing neurodegeneration in cell and animal models, also induces necrosis. Methods: This report includes analysis of COVID-19 positivity by zip codes in Florida and relation of the positivity to population density, possible effect of ecological and social factors on spread of COVID-19, autopsy analysis of COVID-19 cases from around the world, serum metabolomics analysis, and evaluation of autoantigenome related to COVID-19. Results: In the present estimations, COVID-19 positivity percent per zip code population varied in Florida from 4.65% to 44.3% (February 2021 data). COVID-19 analysis is partially included in my book Microbial Metabolism and Disease (2021). The autoantigenome related to COVID-19 is characterized by alterations in protein biosynthesis proteins including aminoacyl-tRNA synthetases. Protein biosynthesis alteration is a feature of Alzheimer’s disease. Serum metabolomics of COVID-19 positive patients show alteration in shikimate pathway metabolism, which is associated with the presence of Alzheimer’s disease-associated human gut bacteria. Conclusion: Such alterations in microbial metabolism and protein biosynthesis can lead to toxicity and neurodegeneration as described earlier in my book Protein Biosynthesis Interference in Disease (2020).

N-nitrosamines, heterocyclic amines, polycyclic aromatic hydrocarbons, biogenic amines, and acrylamide are widely distributed and some of the most toxic substances detected in foods. Hence, reduction of these substances has attracted worldwide attention. Lactic acid bacteria (LAB) inoculation has been found to be an effective way to reduce these toxic substances. In this paper, the reduction of toxic substances by LAB and its underlying mechanisms have been described through the review of recent studies. LAB aids this reduction via different mechanisms. First, it can directly decrease these harmful substances through adsorption or degradation. Peptidoglycans on the cell wall of LAB can bind to heterocyclic amines, acrylamide, and polycyclic aromatic hydrocarbons. Second, LAB can indirectly decrease the content of toxic substances by reducing their precursors. Third, antioxidant properties of LAB also contribute to the reduction in toxic substances. Finally, LAB can suppress the growth of amino acid decarboxylase-positive bacteria, thus reducing the accumulation of biogenic amines and N-nitrosamines. Therefore, LAB can contribute to the decrease in toxic substances in food and improve food safety. Further research on increasing the reduction efficiency of LAB and deciphering the mechanisms at a molecular level needs to be carried out to obtain the complete picture.

Urinary 5-hydroxyindoleacetic acid (5-HIAA), vanillylmandelic (VMA), homovanillic acid (HVA), catecholamines and metanephrines are produced in excess by catecholamine-producing tumors. These biogenic amines are unstable at low or high pH and require hydrochloric acid (HCl) to prevent their degradation. However, HCl addition may result in very low pH causing degradation or deconjugation of several metabolites. This study evaluated the buffering properties of sodium citrate to stabilize all biogenic amines. The metabolite concentrations were measured by LC-MS/MS or by a coulometric assay in 22 urine samples collected native and with HCl or sodium citrate. We studied the effect of pH, time (48 h, four weeks) and storage temperature at 22 °C, 4 °C, and −20 °C. We found that catecholamines degradation was prevented by HCl and citrate and that 5-HIAA was degraded in 5 out of 22 samples collected with HCl. All biogenic amines were efficiently stabilized by citrate for four weeks at 22 °C, except epinephrine (48 h at 4 °C, or four weeks at −20 °C). Sodium citrate did not cause quantification or analytical artefacts concerns. In conclusion, sodium citrate is a non-hazardous alternative to HCl for patients to send unfrozen urine samples to the laboratory which may safely store the sample for four weeks.

Aim . Studying the influence of the features of aminergic brain status on the development of B16/F10 melanoma in mice with urokinase gene knockout and chronic neurogenic pain (CNP). Material and methods . The study included female ( n = 68) С57ВL/6 mice with the normal urokinase gene (+ uPA ) and C57BL/6-PlautmI.IBug-This Plau6FDhu/GFDhu mice with urokinase gene knockout (– uPA ). The model of CNP was created in the animals, and in 14 days B16/F10 melanoma was transplanted. The mice were euthanized 21 days after the transplantation. Levels of adrenaline (A), noradrenaline (NA), dopamine (DA), histamine (H), serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA) were determined in the brain using standard ELISA test systems (Cusabio, China). Results . CNP in (+ uPA ) females resulted in the reduction of almost all studied biogenic amines (BA). On the opposite, (– uPA ) females showed an increase in NA, DA, 5HT and a decrease of H. 5HIAA increased in both CNP and gene knockout. 5HT in (+ uPA ) females with CNP decreased, while its physiological level in gene knockout mice was maintained. After 3 weeks of tumor growth in animals with CNP, (+ uPA ) mice demonstrated increased levels of studied BA (except for 5HIAA) compared to mice with CNP alone. Only H increase was observed in (– uPA ) mice from the similar group. Conclusion. CNP in mice inhibited A-, NA-, H- and 5HT-ergic systems of the brain; the opposite effects were registered in urokinase gene knockout, except for the H-ergic system. Combination of CNP and melanoma in (+ uPA ) female mice activated all studied BA systems, and in (– uPA ) females – H-ergic system only. Different stressful effects, CNP, and genetic disorders (urokinase gene knockout) contributed to changes in the brain BA system functions, leading to the activation of pro- or antitumor mechanisms.

Biogenic amines (BA) are organic compounds commonly found in food, plants and animals, as well as microorganisms that are attributed with the production of BAs. They are formed as an effect of a chemical process: the decarboxylation of amino acids. Factors determining the formation of BAs include the availability of free amino acids and the presence of microorganisms that show activity with respect to carrying out the decarboxylation process. On the one hand, BAs are compounds that are crucial for maintaining cell viability, as well as the proper course of the organism's metabolic processes, such as protein synthesis, hormone synthesis and DNA replication. On the other hand, despite their positive effects on the functioning of the organism, an excessive content of BAs proves to be toxic (diarrhea, food poisoning, vomiting, sweating or tachycardia). Moreover, they can accelerate carcinogenesis. Amines are a natural component of plant and animal raw materials. As a result of the proven negative effects of amines on living organisms, the reduction of these compounds should be the subject of scientific research. The present review aims to synthesize and summarize the information currently available on BAs, as well as discuss the interpretation of the results. © 2020 Society of Chemical Industry.

Background Eleven Lactobacillus (L.) strains were newly isolated from traditional Turkish Tulum cheeses and were characterized regarding their potential probiotic characteristics (bile and acid tolerance, gastric and pancreatic juice tolerance, lysozyme tolerance, adhesion ability), virulence determinants (hemolytic activity, antibiotic resistance, biogenic amine production), and functional properties (antibacterial activity, β-galactosidase activity, production of exopolysaccharides, cholesterol removal). Results These isolates were identified as L. brevis, L. plantarum, L. paracasei, L. coryniformis, L. rhamnosus and L. helveticus by 16S rRNA sequencing. With regard to safety aspects, none of the tested Lactobacillus isolates showed hemolytic activity or biogenic amine production. All the Lactobacillus isolates except isolate 24 were found to be sensitive or intermediate sensitive to penicillin, which is a frequently used antibiotic. Nine Lactobacillus isolates showed antibacterial activity against Staphylococcus aureus ATCC 25923, while only isolates 15 and 449 exhibited inhibitory activity against Listeria monocytogenes ATCC 7644. All isolated strains survived, even in the presence of 10.00 g L-1 bile after 48 h, and exhibited good survival at pH 3, but only two isolates survived at pH 2. Among the strains, isolate 15 exhibited satisfactory auto-aggregative, cell-surface hydrophobicity features, cholesterol-lowering activity and good acid tolerance. Isolate 15 also showed the strongest bile and simulated pancreatic juice resistance and moderate lysozyme tolerance. Conclusion These outcomes suggest that isolate 15, identified as a L. plantarum strain from Tulum cheese, may be a promising probiotic candidate and could be suitable for use in several fermented foods. © 2020 Society of Chemical Industry.

Shrimps fishing, especially the pink (Farfantepenaeus brasiliensis and F. subtilis) and the white (Litopenaeus schmitti) ones, are relevant for the Brazilian Northeast economy, and their price depends on their aspect-quality. They are rich in lipids/proteins, which are a target for autolytic and microbial enzymes. These may not change the shrimps’ appearance but generate substances that may cause poisoning, as histamines. This work compared the microbial quality of fillets and shells of these three shrimps, harvested in two years, after cooking and storage under different freezing times (0- 90 days), as well as the total carotenoids (TC) and antioxidant activity (AA%) of ethanolic extracts from all the samples, using spectrophotometry and DPPH test. None histaminogenic and few mesophilic bacteria were isolated (all Gram+ species of Corynebacterium, Listeria, Arthrobacter, Bacillus and Erysipelothrix), but in lower number than the tolerability limit. The TC and AA% of fresh shells from time “zero” were always higher than those of fillets, mainly for F. subtilis. Cooking increased TC and AA% of fillets, but reduced them in shells, and both parameters declined along the freezing. Thin-layer chromatography and spectrophotometric scanning of all the extracts and standards evidenced astaxanthin as the main carotenoid.

Memory retrieval is mediated by discharges of acetylcholine, glutamate, gammaaminobutyric acid, norepinephrine, and serotonin/5-hydroxytryptamine circuits. These projections and memory interact through engram circuits, neurobiological traces of memory. Increased excitability in engram circuits of the medial prefrontal cortex and hippocampus results in remote and recent memory retrievals, respectively. However, due to degenerated neurotransmitter projections, the excitability state of engram circuits is decreased in the patient with dementia; and thus, acquired- memory cannot be retrieved by natural cues. Here, we suggest that artificial neuropharmacological stimulations of the acquired-memory with an excitation potential higher than a natural cue can excite engram circuits in the medial prefrontal cortex, which results in the retrieval of lost memories in dementia. The neuropharmacological foundations of engram cell-mediated memory retrieval strategy in severe dementia, in line with this has also been explained. We particularly highlighted the close interactions between periaqueductal gray, locus coeruleus, raphe nuclei, and medial prefrontal cortex and basolateral amygdala as treatment targets for memory loss. Furthermore, the engram circuits projecting raphe nuclei, locus coeruleus, and pontomesencephalic tegmentum complex could be significant targets of memory editing and memory formation in the absence of experience, and a well-defined study of the neural events underlying the interaction of brain stem and memory will be relevant for such developments. We anticipate our perspective to be a starting point for more sophisticated in vivo models for neuropharmacological modulations of memory retrieval in Alzheimer’s dementia.

Neoadjuvant treatment (NAT) can downstage breast cancer and can be utilized for different clinical applications. However, the response to NAT varies among individuals. Having effective biomarkers is important to optimize the treatment of breast cancer. Concentrations of biogenic amines have been found to show an association with cancer cell proliferation, but their clinical utility remains unclear. This study developed a postcolumn-infused internal standard (PCI-IS)-assisted liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) method for profiling biogenic amines in human urine. Putrescine-d8 was selected as the PCI-IS to calibrate the errors caused by matrix effects in the urine sample. The optimized method was applied to investigate the association between changes in 14 amines and the therapeutic response to NAT in breast cancer patients. Urine samples were collected before initiation of chemotherapy (n = 60). Our results indicated that the levels of N1-acetylspermine, spermidine, norepinephrine, and dopamine were significantly higher in the responder group than the nonresponder group. These metabolites were incorporated with clinical factors to identify NAT responders, and the prediction model showed an area under the curve value of 0.949. These observations provide remarkable insights for future studies in elucidating the roles of biogenic amines in breast cancer. Additionally, the PCI-IS-assisted amine profiling method can facilitate these studies.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with neurodegenerative processes, that may also aid in identifying potential drug targets. The current study therefore investigated associations between plasma neurofilament light chain (NF-L), a marker of neurodegeneration, with plasma metabolites that are products of various cellular processes. Plasma NF-L, measured by ultrasensitive Single molecule array (Simoa) technology (Quanterix) and plasma metabolites, measured by mass-spectrometry (AbsoluteIDQ® p400HR kit, BIOCRATES), were assessed in the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort comprising 100 cognitively normal older adults. Metabolites belonging to biogenic amine (creatinine, symmetric dimethylarginine, asymmetric dimethylarginine; ADMA, kynurenine, trans-4-hydroxyproline), amino acid (citrulline, proline, arginine, asparagine, phenylalanine, threonine) and acylcarnitine classes were observed to have positive correlations with plasma NF-L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Additionally, after stratifying participants based on low/high brain amyloid-β load (Aβ ±) assessed by positron emission tomography, while creatinine, SDMA and citrulline correlated with NF-L in both Aβ- and Aβ+ groups, ADMA, proline, arginine, asparagine, phenylalanine and acylcarnitine species correlated with NF-L only in the Aβ+ group after adjusting for confounding variables, suggesting that the association of these metabolites with neurodegeneration may be relevant to AD-related neuropathology. Metabolites identified to be associated with plasma NF-L may have the potential to serve as prognostic markers for neurodegenerative diseases, however, further studies are required to validate the current findings in an independent cohort, both cross-sectionally and longitudinally.

New neuroprotective treatments of natural origin are being investigated. Both, plant extracts and isolated compounds have shown bioactive effects. Hempseed is known for its composition of fatty acids, proteins, fibre, vitamins, as well as a large number of phytochemical compounds. After a defatting process of the seeds, hydroxycinnamic acids and its amine derivatives are the majoritarian compounds in an ethyl acetate fraction (EAF). In the present study, we investigated

Many women suffer from urinary tract infections (UTIs). In addition to pain and increased urgency to urinate, malodour is a significant issue for these patients. The specific factors causing this malodour are unclear, and there are no targeted treatment options to counteract it effectively. We used a metabolomics approach to compare the chemical composition of metabolites in the urine of women with E. coli UTIs (n = 15) and those who are healthy (n = 10). The biogenic amines trimethylamine and putrescine, which cause malodour in other urogenital conditions, were significantly increased in UTI patients. Conversely, the precursor of trimethylamine, trimethylamine N-oxide, was lower. To further confirm the source of the malodorous compounds, in vitro experiments were conducted by incubating strains of uropathogenic E. coli in sterilized urine from healthy women. All tested strains accumulated trimethylamine and putrescine. Notably, cadaverine was also produced by E. coli strains in vitro; however, it was not significantly different between both groups. We confirmed that the malodorous amines TMA and putrescine are found in higher concentrations in the urine of patients with an E.coli-caused UTI.

The objective of this study was to evaluate whether whole raw milk originating from Holstein dairy cows affected by lameness alters its composition. A total of 20 healthy control cows and 6 cows diagnosed with lameness were selected out of 100 sampled cows in a nested case control study at 2 weeks postpartum, and whole raw milk samples were collected and analyzed with direct inject/liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance. In total, 168 metabolites were identified and quantified using an in-house mass spectrometry library. A total of 35 of the identified metabolites decreased versus control cows. Only two metabolites (i.e., sn-glycero-3-phosphocholine and phosphatidylethanolamine ae C42:1) were increased in the milk of lame cows. In conclusion, milk metabotyping of lame cows revealed significant changes in multiple milk components, including amino acids, lipids, and biogenic amines. Most of the milk compounds identified as altered were lowered, suggesting deflection of nutrients from the mammary gland to the host needs for healing lameness-associated pathological processes.

Depression is still one of challenging, and widely encountered disorders with complex etiology. The role of healthy diet and olive oil in ameliorating depression has been claimed. This study was designed to explore the effects of oleuropein; the main constituent of olive oil; on depression-like behaviors that are induced by repeated administration of corticosterone (40 mg/kg, i.p.), once a day for 21 days, in mice. Oleuropein (8, 16, and 32 mg/kg, i.p.) or fluoxetine (20 mg/kg, positive control, i.p.1) was administered 30 minutes prior to corticosterone injection. Sucrose consumption test, open-field test (OFT), tail suspension test (TST), and forced swimming test (FST) were performed. Reduced Glutathione (GSH), lipid peroxidation, and biogenic amines; serotonin, dopamine, and nor-epinephrine; levels were also analyzed in brain homogenates. Corticosterone treatment induced depression-like behaviors, it increased immobility time in the TST, OFT, and FST, decreased the number of movements in OFT, and decreased sucrose consumption. Corticosterone effect was associated with depletion of reduced glutathione and increase of lipid peroxidation, in addition to modification of biogenic amines; decreased serotonin and dopamine. Oleuropein or fluoxetine administration counteracted corticosterone-induced changes. In conclusion, oleuropein showed a promising antidepressant activity, that is evident by improving corticosterone-induced depression-like behaviors, and normalizing levels of biogenic amines.

Neuropathic pain is a chronic pain caused by central and peripheral nerve injury, long-term diabetes or treatment with chemotherapy drugs, and it is dissimilar to other chronic pain conditions. Chronic pain usually seriously affects the quality of life, and its drug treatment may result in increased costs of social and medical care. As in the USA and Canada, in Europe, the demand for pain-relieving medicines used in chronic pain has also significantly increased, but most European countries are not experiencing an opioid crisis. In this review, the role of various endogenous transmitters (noradrenaline, dopamine, serotonin, met- and leu-enkephalins, β-endorphin, dynorphins, cannabinoids, ATP) and various receptors (α2, μ, etc.) in the innate pain-relieving system will be discussed. Furthermore, the modulation of pain processing pathways by transmitters, focusing on neuropathic pain and the role of the sympathetic nervous system in the side effects of excessive opioid treatment, will be explained.

This study presents the development of disposable biosensors employed in the determination of histamine in fish samples. Screen printed carbon electrodes (SPCEs) were first modified with a mixture of titanium dioxide nanoparticles (TiO2), carboxylated multiwalled carbon nanotubes (c-MWCNTs), hexaammineruthenium(iii) chloride (RU) and chitosan (CS). Diamine oxidase (DAO) or monoamine oxidase (MAO) enzymes were further immobilized onto the TiO2-c-MWCNT-RU-CS/SPCEs via 1-ethyl-3-(dimethylaminopropyl) carbodiimide hydrochloride (EDC) and hydroxysuccinimide (NHS) chemistry for the fabrication of the biosensors. The morphological and electrochemical properties of the proposed biosensors were studied using scanning electron microscopy (SEM), energy dispersive X-ray (EDX) spectroscopy, cyclic voltammetry (CV), chronoamperometry and electrochemical impedance spectroscopy (EIS). A performance comparison of two biosensors indicated that the one based on DAO had a linear concentration range from 9.9 × 10-6 to 1.1 × 10-3 M and the other based on MAO, from 5.6 × 10-5 to 1.1 × 10-3 M for histamine. The sensitivity of the DAO based biosensor was almost 1.5 times higher than that of the MAO based biosensor. The proposed biosensors were successfully employed to determine histamine in fish samples and the recoveries were between 100.0% and 104.6%.

The coordination between the animal’s external environment and internal state requires constant modulation by chemicals known as neuromodulators. Neuromodulators, such as biogenic amines, neuropeptides and cytokines, promote organismal homeostasis. Over the past several decades, Caenorhabditis elegans has grown into a powerful model organism that allows the elucidation of the mechanisms of action of neuromodulators that are conserved across species. In this perspective, we highlight a collection of articles in this issue that describe how neuromodulators optimize C. elegans survival.

In the present study, we characterize a novel zebrafish mutant of solute carrier 18A2 (slc18a2), also known as vesicular monoamine transporter 2 (vmat2), that exhibits a behavioural phenotype partially consistent with human Parkinson's disease. At six days-post-fertilization, behaviour was analysed and demonstrated that vmat2 homozygous mutant larvae, relative to wild types, show changes in motility in a photomotor assay, altered sleep parameters, and reduced dopamine cell number. Following an abrupt lights-off stimulus mutant larvae initiate larger movements but subsequently inhibit them to a lesser extent in comparison to wild-type larvae. Conversely, during a lights-on period, the mutant larvae are hypomotile. Thigmotaxis, a preference to avoid the centre of a behavioural arena, was increased in homozygotes over heterozygotes and wild types, as was daytime sleep ratio. Furthermore, incubating mutant larvae in pramipexole or L-Dopa partially rescued the motor phenotypes, as did injecting glial cell-derived neurotrophic factor (GDNF) into their brains. This novel vmat2 model represents a tool for high throughput pharmaceutical screens for novel therapeutics, in particular those that increase monoamine transport, and for studies of the function of monoamine transporters. This work is funded in part by grants from the National Institutes of Health GM067841 (RAC) and AR062547 (RAC). NO The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Biogenic amines (BAs) are low molecular weight organic bases. BAs occurring naturally in living organisms are responsible for a number of vital functions, including (in humans) secretion of gastric acids, controlling body temperature, differentiation and growth of cells, immune reactions, and brain activity. However, if oversupplied with food, BAs may cause food poisoning and produce undesirable effects. Nine BAs and eight free amino acids (FAAs) were determined in 85 samples of 19 different varieties of fermented vegetables available on the Polish retail market. Both BA and FAA levels differed significantly among various varieties of the studied fermented vegetables. Averages for the sum of all tested BAs ranged from 30.29 ± 16.43 mg·kg-1 in fermented olives to 612.1 ± 359.33 mg·kg-1 in fermented Brussels sprout. BA profiles were dominated by putrescine (42%), tyramine (20%), cadaverine (18%), and histamine (8%); jointly, the four amines amounted to 88% of all nine studied BAs. The combined level of the latter four BAs was calculated for each vegetable variety as the so-called BA index (BAI). On that basis, the risk of BA-related adverse health effects has been assessed as high/medium/low in 6/3/10 of all 19 studied varieties of fermented vegetables. Brussels sprout and broccoli turned out to be the most risky vegetables from that point of view (BAI above 400 mg·kg-1). FAA levels ranged from 54.8 ± 12.76 (fermented olives) to 3917.42 ± 1528.73 mg·kg-1 (fermented garlic). The high content of FAAs may increase the risk of forming toxic amounts of BAs, depending on characteristics of the current and added microflora as well as on environmental and technological conditions the product is subjected to.

Biogenic amines, such as adrenaline, noradrenaline, histamine, dopamine, and serotonin are important neurotransmitters that also regulate cell viability. Their detection and analysis are helpful in the diagnosis of many diseases, including cancer. The aim of this study was to determine the expression profile of the biogenic amine-related genes and proteins in endometrioid endometrial cancer compared to the control group. The material consisted of endometrial tissue samples and whole blood collected from 30 endometrioid endometrial cancer patients and 30 cancer-free patients. The gene expression was determined by the mRNA microarrays and validated by qRT-PCR. Protein levels were determined in the serum by the enzyme-linked immunosorbent assay (ELISA). Overexpression of histamine H1–H3 receptors and early growth response 1 and silencing of calmodulin, the histamine H4 receptor, and the dopamine D5 receptor have been reported in endometrioid endometrial cancer. The obtained results indicate disturbances in the signaling activated by histamine and dopamine receptors, which could potentially contribute to the progression of endometrioid endometrial cancer.

Monoamine neurotransmitter disorders present predominantly with neurologic features, including dystonic or dyskinetic cerebral palsy and movement disorders. Genetic conditions that lead to secondary defects in the synthesis, catabolism, transport, and metabolism of biogenic amines can lead to neurotransmitter abnormalities, which can present with similar features. Eleven patients with secondary neurotransmitter abnormalities were enrolled between 2011 and 2015. All patients underwent research-based whole exome and/or whole genome sequencing (WES/WGS). A trial of treatment with levodopa/carbidopa and 5-hydroxytryptophan was initiated. In six families with abnormal neurotransmitter profiles and neurological phenotypes, variants in known disease-causing genes (KCNJ6, SCN2A, CSTB in 2 siblings, NRNX1, KIF1A and PAK3) were identified, while one patient had a variant of uncertain significance in a candidate gene (DLG4) that may explain her phenotype. In 3 patients, no compelling candidate genes were identified. A trial of neurotransmitter replacement therapy led to improvement in motor and behavioral symptoms in all but two patients. The patient with KCNJ6 variant did not respond to L-dopa therapy, but rather experienced increased dyskinetic movements even at low dose of medication. The patient’s symptoms harboring the NRNX1 deletion remained unaltered. This study demonstrates the utility of genome-wide sequencing in further understanding the etiology and pathophysiology of neurometabolic conditions, and the potential of secondary neurotransmitter deficiencies to serve as novel therapeutic targets. As there was a largely favorable response to therapy in our case series, a careful trial of neurotransmitter replacement therapy should be considered in patients with cerebrospinal fluid (CSF) monoamines below reference range.

In this study, comparative analyses were carried out with ion chromatography mass-spectrometry (IC-MS/MS) which has no derivatization step, high-performance liquid chromatography (HPLC) technique, as well as two quantitative and two semi-quantitative immunoassays. The results demonstrated that HPLC and quantitative immunoassay methods were well-correlated with IC-MS/MS in determining histamine in various types of fish products. The best correlation was observed with the HistaSure ELISA Fast Track kit (R2 = 0.9903). More than half of the values (68%) obtained by two methods were also statistically similar. The results of semi-quantitative test kits also supported histamine values estimated by quantitative methods, with some exceptions. The best results were found for HistaSure Lateral Flow in supporting the quantitative techniques. Therefore, these methods are found suitable for monitoring histamine in fish products in terms of food safety. Good correlations were also observed HPLC and IC-MS/MS in determining cadaverine, putrescine, and tyramine with the highest value observed for tyramine as R2 = 0.9785. However, no correlation was observed for other biogenic amines, and the majority of the results were significantly different from each other for these amines (p &lt, 0.05). The differences may be caused by the drawbacks reported previously for HPLC. However, further studies are required to confirm the possible effects. This study provides a comparative evaluation of several methods in terms of their suitability in determining biogenic amines in fish products for both monitoring and regulatory purposes.

BackgroundThe development of new non-surgical treatments dedicated to mitral valve degeneration is limited by the absence of relevant spontaneous and rapidly progressing animal experimental models.AnimalsWe characterized the spontaneous mitral valve degeneration in two inbred FVB mouse strains compared to C57BL/6J and investigated a contribution of the serotonergic system.MethodsMales and females FVB/NJ and FVB/NRj were compared to the putative C57BL/6J control at 12, 16, 20 and 24 weeks of age. Body weight, systolic blood pressure, heart rate, urinary 5-hydroxyindoleacetic acid (5-HIAA), whole blood and plasma serotonin, tail bleeding time, blood cell count, plasma TGF-β1 and plasma natriuretic peptide concentrations were measured. Myocardium and mitral valves were characterized by histology. mRNA mitral expression of 5-HT2A and 5-HT2B receptors was measured in the anterior leaflet. Cardiac anatomy and function were assessed by echocardiography.ResultsCompared to C57BL/6J, FVB mice strains did not significantly differ regarding body weight increase, arterial blood pressure and heart rate. A progressive augmentation of plasma pro-ANP was observed in FVB mice. Nevertheless, no cardiac hypertrophy or left-ventricular fibrosis were observed. Accordingly, plasma TGF-β1 was not different among the three strains. Conversely, FVB mice demonstrated a high prevalence of fibromyxoid highly cellularized and enriched in glycosaminoglycans lesions, inducing major mitral leaflets thickening without increase in length. The increased thickness was correlated with urinary 5-HIAA and blood platelet count. Whole blood serotonin concentration was similar in the two strains but, in FVB, a reduction of plasma serotonin was observed together with an increase of the bleeding time. Finally, echocardiography identified left atrial and left ventricular remodeling associated with thickening of both mitral leaflets and mitral insufficient in 30% of FVB mice but no systolic protrusion of mitral leaflets towards the atrium.ConclusionThe FVB mouse strain is highly prone to spontaneous mitral myxomatous degeneration. A contribution of the peripheral serotonergic system is suggested.

Two subpopulations of midbrain dopamine (DA) neurons are known to have different dynamic firing ranges in vitro that correspond to distinct projection targets: the originally identified conventional DA neurons project to the dorsal striatum and the lateral shell of the nucleus accumbens, whereas an atypical DA population with higher maximum firing frequencies projects to prefrontal regions and other limbic regions including the medial shell of nucleus accumbens. Using a computational model, we show that previously identified differences in biophysical properties do not fully account for the larger dynamic range of the atypical population and predict that the major difference is that originally identified conventional cells have larger occupancy of voltage-gated sodium channels in a long-term inactivated state that recovers slowly; stronger sodium and potassium conductances during action potential firing are also predicted for the conventional compared to the atypical DA population. These differences in sodium channel gating imply that longer intervals between spikes are required in the conventional population for full recovery from long-term inactivation induced by the preceding spike, hence the lower maximum frequency. These same differences can also change the bifurcation structure to account for distinct modes of entry into depolarization block: abrupt versus gradual. The model predicted that in cells that have entered depolarization block, it is much more likely that an additional depolarization can evoke an action potential in conventional DA population. New experiments comparing lateral to medial shell projecting neurons confirmed this model prediction, with implications for differential synaptic integration in the two populations., Author summary We developed a theoretical and mathematical framework that could explain the major electrophysiological differences between the conventional midbrain dopamine (DA) neurons with a low maximum firing rate, and the more recently identified atypical DA neurons. Testable predictions from this framework were then verified with in vitro patch-clamp recordings from DA neurons with identified phenotypes and projection targets. Since different subpopulations of DA neurons participate in different circuits, and these circuits are likely differentially dysregulated in diseases such as addiction, Parkinson disease, and schizophrenia, it is important to identify the differences of their intrinsic electrophysiological properties as a prelude to developing more precisely targeted therapies.

Simple Summary Appetite regulation is an important function necessary to maintain energetic balance, but how honey bees accomplish this could vary as they age because they go through a number of behavioral and physiological changes during development. Here, we determine if the amount of trehalose, which is a sugar found in the hemolymph of honey bees, influences appetite levels and if this interacts with the octopamine neurotransmitter in the bee brain. To accomplish this, we decreased trehalose levels in the hemolymph by injecting an inhibitor of trehalose synthesis. In addition, we increased octopamine levels in the brain by injecting it with a syringe. We found that octopamine and trehalose interact to increase appetite in the two older age classes of bees, beyond just treating the bees with octopamine. The youngest age class did not respond to either treatment. Our results suggest that older honey bees may have an alternative pathway for regulating appetite that uses sugar levels in their hemolymph to communicate to the brain how hungry they are and that octopamine is responsible for elevating appetite levels when the bee is hungry. This pathway is different from how vertebrates regulate their appetite levels based on glucose levels in the blood. Abstract There are multiple feedback mechanisms involved in appetite regulation, which is an integral part of maintaining energetic homeostasis. Older forager honey bees, in comparison to newly emerged bees and nurse bees, are known to have highly fluctuating hemolymph trehalose levels, higher appetite changes due to starvation, and higher octopamine levels in the brain. What remains unknown is if the hemolymph trehalose and octopamine levels interact with one another and how this varies as the bee ages. We manipulated trehalose and octopamine levels across age using physiological injections and found that nurse and forager bees increase their appetite levels due to increased octopamine levels in the brain. This is further enhanced by lower trehalose levels in the hemolymph. Moreover, nurse bees with high octopamine levels in the brain and low trehalose levels had the same appetite levels as untreated forager bees. Our findings suggest that the naturally higher levels of octopamine as the bee ages may result in higher sensitivity to fluctuating trehalose levels in the hemolymph that results in a more direct way of assessing the energetic state of the individual. Consequently, forager bees have a mechanism for more precise regulation of appetite in comparison to newly emerged and nurse bees.

Trace amine-associated receptors (TAARs) are a group of G protein-coupled receptors that are expressed in the olfactory epithelium, central nervous system, and periphery. TAAR family generally consists of nine types of receptors (TAAR1-9), which can detect biogenic amines. During the last 5 years, the TAAR5 receptor became one of the most intriguing receptors in this subfamily. Recent studies revealed that TAAR5 is involved not only in sensing socially relevant odors but also in the regulation of dopamine and serotonin transmission, emotional regulation, and adult neurogenesis by providing significant input from the olfactory system to the limbic brain areas. Such results indicate that future antagonistic TAAR5-based therapies may have high pharmacological potential in the field of neuropsychiatric disorders. TAAR5 is known to be expressed in leucocytes as well. To evaluate potential hematological side effects of such future treatments we analyzed several hematological parameters in mice lacking TAAR5. In these mutants, we observed minor but significant changes in the osmotic fragility test of erythrocytes and hematocrit levels. At the same time, analysis of other parameters including complete blood count and reticulocyte levels showed no significant alterations in TAAR5 knockout mice. Thus, TAAR5 gene knockout leads to minor negative changes in the erythropoiesis or eryptosis processes, and further research in that field is needed. The impact of TAAR5 deficiency on other hematological parameters seems minimal. Such negative, albeit minor, effects of TAAR5 deficiency should be taken into account during future TAAR5-based therapy development.

Modern techniques for estimating basal levels of electroactive neurotransmitters rely on the measurement of oxidative charges. This requires time integration of oxidation currents at certain intervals. Unfortunately, the selection of integration intervals relies on ad-hoc visual identification of peaks on the oxidation currents, which introduces sources of error and precludes the development of automated procedures necessary for analysis and quantification of neurotransmitter levels in large data sets. In an effort to improve charge quantification techniques, here we present novel methods for automatic selection of integration boundaries. Our results show that these methods allow quantification of oxidation reactions both in vitro and in vivo and of multiple analytes in vitro.

Research Areas: Environmental Sciences & Ecology ; Public, Environmental & Occupational Health : Dry-cured sausages are traditional in Mediterranean countries, and Paio do Alentejo (PA) is one of the most popular in South Portugal. The aim of the present work was to evaluate the effect of combined starters on the safety and quality of PA preserving its sensory quality. Physicochemical parameters, namely pH and water activity (aW), microbiological parameters, biogenic amines, color, texture, and sensory attributes were assessed. Three starter cultures were used, namely Staphylococcus equorum S2M7 and Lactobacillus sakei CV3C2, both separate and combined with the 2RB4 yeast strain at a concentration of 106 cfu/g. Dextrose 0.25% was added to the meat batter. Starters had a significant effect on the reduction of aW values (0.845 to 0.823). The treatment with L. sakei as well as the co-inoculation of L. sakei with S. equorum effectively reduced the L. monocytogenes counts to undetectable levels. Sausages co-inoculated with S. equorum S2M7/L. sakei CV3C2 showed a significant reduction in the content of vasoactive amines, namely tryptamine (26.21 to 15.70) and β-phenylethylamine (4.80 to 3.69). Regarding texture, control PA showed higher hardness values, and the starters promoted the cohesiveness of the batter while reducing chewiness. The studied starters did not compromise the sensory characteristics of PA. info:eu-repo/semantics/publishedVersion

Keratinocyte migration into skin wounds is the step of the healing process that correlates with the wound closure rate. Keratinocyte migration, and wound epithelialization are decreased when beta 2-adrenergic receptors (B2AR) are activated by 1 μM epinephrine/adrenaline, resulting in delayed wound healing in human and mouse skin. In the present study, we found paradoxically, that in a subset of keratinocyte strains exposure to low concentrations of epinephrine (0.1 nM) increased, rather than decreased, their migratory rate. We find that both the alpha- and the beta-adrenergic receptors are expressed in human keratinocytes, and expression of alpha-2 AR subtypes demonstrated for the first time. Therefore, we tested if the alpha-AR could be modulating the increased migratory response observed in these cell strains. By using specific inhibitors to alpha-AR, we demonstrated that blocking A2B-AR could reverse the rapid cell migration induced by the 0.1 nM epinephrine. Phosphorylation of ERK was elevated after 1–10 minutes of the low epinephrine treatment and the A2B-AR inhibitor blocked the ERK phosphorylation. The results suggest that both the A2B-AR and B2AR mediate keratinocyte migration, in which with a low level of epinephrine treatment, A2B-AR could alter the B2AR signals and regulate the migration rate.

Backgrounds We demonstrated that coronary adventitial inflammation plays important roles in the pathogenesis of drug-eluting stent (DES)-induced coronary hyperconstricting responses in pigs in vivo. However, no therapy is yet available to treat coronary adventitial inflammation. We thus developed the low-intensity pulsed ultrasound (LIPUS) therapy that ameliorates myocardial ischemia by enhancing angiogenesis. Aims We aimed to examine whether our LIPUS therapy suppresses DES-induced coronary hyperconstricting responses in pigs in vivo, and if so, what mechanisms are involved. Methods Sixteen normal male pigs were randomly assigned to the LIPUS or the sham therapy groups after DES implantation into the left anterior descending (LAD) coronary artery. In the LIPUS group, LIPUS (32 cycles, 193 mW/cm2) was applied to the heart at 3 different levels (segments proximal and distal to the stent edges and middle of the stent) for 20 min at each level for every other day for 2 weeks. The sham therapy group was treated in the same manner but without LIPUS. At 4 weeks after stent implantation, we performed coronary angiography, followed by immunohistological analysis. Results Coronary vasoconstricting responses to serotonin in LAD at DES edges were significantly suppressed in the LIPUS group compared with the sham group. Furthermore, lymph transport speed in vivo was significantly faster in the LIPUS group than in the sham group. Histological analysis at DES edges showed that inflammatory changes and Rho-kinase activity were significantly suppressed in the LIPUS group, associated with eNOS up-regulation and enhanced lymph-angiogenesis. Conclusions These results suggest that our non-invasive LIPUS therapy is useful to treat coronary functional abnormalities caused by coronary adventitial inflammation, indicating its potential for the novel and safe therapeutic approach of coronary artery disease.

Background Anxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis. Methods and findings We searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies’ databases. No restriction was made regarding comorbidities with any other mental disorder, participants’ age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration’s risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective than placebo for the aggregate measure of internalizing symptoms (SMD −0.56, 95% CI −0.62 to −0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials. Conclusions In this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy., In a meta-analysis of randomized trials, Natan Pereira Gosmann and colleagues study efficacy of SSRIs and SNRIs for symptoms of anxiety, obsessive-compulsive, and stress-related disorders., Author summary Why was this study done? Studies assessing comorbidity in patients with anxiety, obsessive-compulsive, and stress-related disorders report rates above 50%, and patients often present symptoms of multiple symptom domains. The efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) on multiple mental health domains has not yet been studied by network meta-analysis in this field, to the best of our knowledge. Meta-analyses often restrain the statistical analysis to the most commonly used assessment instruments. What did the researchers do and find? We conducted a systematic review and 3-level network meta-analysis of 469 outcome measures, including all available measures of outcomes related to anxiety, obsessive-compulsive, and stress-related disorders. SSRIs and SNRIs presented small to moderate effect sizes for global improvement of mental health in participants from all diagnostic categories. We also found small to moderate effect sizes in our sensitivity analysis restricted to the most used assessment instruments; however, this restriction led to the exclusion of 72.71% of all outcome measures. What do these findings mean? Our results support previous findings related to the efficacy of SSRIs and SNRIs indicating that these medications are effective in multiple health domains. This study improved the evidence of the benefit of SSRIs and SNRIs for anxiety disorders. These results should guide psychiatrists, patients, clinicians, and policy makers on better evidence-based decisions for the initial treatment of these disorders.

To survive, animals have to quickly modify their behaviour when the reward changes. The internal representations responsible for this are updated through synaptic weight changes, mediated by certain neuromodulators conveying feedback from the environment. In previous experiments, we discovered a form of hippocampal Spike-Timing-Dependent-Plasticity (STDP) that is sequentially modulated by acetylcholine and dopamine. Acetylcholine facilitates synaptic depression, while dopamine retroactively converts the depression into potentiation. When these experimental findings were implemented as a learning rule in a computational model, our simulations showed that cholinergic-facilitated depression is important for reversal learning. In the present study, we tested the model’s prediction by optogenetically inactivating cholinergic neurons in mice during a hippocampus-dependent spatial learning task with changing rewards. We found that reversal learning, but not initial place learning, was impaired, verifying our computational prediction that acetylcholine-modulated plasticity promotes the unlearning of old reward locations. Further, differences in neuromodulator concentrations in the model captured mouse-by-mouse performance variability in the optogenetic experiments. Our line of work sheds light on how neuromodulators enable the learning of new contingencies., Author summary Reversal learning likely involves changes in synaptic connections, a neural mechanism known as synaptic plasticity, so old information can be updated. We previously discovered that acetylcholine, an important neuromodulator in the brain, changes synaptic connections in a way that favours reversal learning. Specifically, acetylcholine weakens active synapses in brain slices, but these synapses can later be strengthened by a reward signal. Based on this result in slices, we used a computational model to propose a behavioural function for the action of acetylcholine on synaptic connections. In the model, acetylcholine would weaken synaptic connections associated with an old reward, allowing an agent to quickly learn a new reward location. We tested this hypothesis here by silencing acetylcholine neurons in mice while they navigated a maze for food rewards. These animals were able to learn the location of the first food reward, but were impaired when the reward was shifted to a new location. The behavioural results of this study suggest that acetylcholine indeed facilitates reversal learning, which the computational model attributes to a weakening of synaptic connections that do not lead to reward. Taken together, our experimental and computational work show how synaptic strength changes, gated by neuromodulators, affect learning behaviour.

Aim To characterize the usage profile and the factors associated with the prolonged use of proton pump inhibitor drugs in a community pharmacy. Methodology This is a cross-sectional, prospective and observational study involving interviews with 410 patients who acquired PPI for their own use from community pharmacies. To characterize the factors associated with the prolonged use of PPI, a multivariate logistic regression model was used. Results Pantoprazole (42.7%) and omeprazole (31%) were the most acquired PPIs, prescribed mainly by gastroenterologists (49.5%). They are used in the morning, especially for gastrointestinal symptoms, however, they had been consumed for more than 5 years in 30% of cases. The factors associated with prolonged use are old age (OR 1.03 CI95% 1.01–1.05), body mass index (OR 1.07 CI95% 1.01–1.12), use of non-steroidal anti-inflammatories (OR 3.18 CI95% 1.20–8.43) and selective serotonin reuptake inhibitors (OR 3.5 95% CI 1.39–8.88). Conclusion PPIs are adequate in terms of indication and form of use, however, prolonged use associated with old age, being overweight and use of anti-inflammatories and antidepressants is frequent.

Salmon flesh spoilage can be greatly reduced through the use of preservation methods, using natural products combined with low temperature and packaging. Microbiological and physicochemical characteristics of fresh salmon fillets ( Salmo salar ), sprayed with an aromatic vinegar and stored in modified atmosphere packaging, were investigated. Fillets were kept at 4°C and sampled after 2 h and 3, 7 and 10 days. An untreated control group was used as well. Fish samples were analysed for microbiological (total viable count, Enterobacteriaceae , psychrotrophic microbial count, Pseudomonas spp.) and physicochemical (pH, colour, total volatile basic nitrogen, and biogenic amines) properties. Aromatic vinegar was found to beneficially contribute to the hygienic quality of the salmon, reducing microbial growth during storage and exerting a positive effect, mainly on psychrotrophic loads and Pseudomonas spp. The treatment had a positive effect on biogenic amine levels, showing lower values for histamine, putrescine, cadaverine, and tyramine.

ST-segment elevation myocardial infarction (STEMI) is the most severe form of myocardial infarction (MI) and the main contributor to morbidity and mortality caused by MI worldwide. Frequently, STEMI is caused by complete and persistent occlusion of a coronary artery by a blood clot, which promotes heart damage. STEMI impairment triggers changes in gene transcription, protein expression, and metabolite concentrations, which grants a biosignature to the heart dysfunction. There is a major interest in identifying novel biomarkers that could improve the diagnosis of STEMI. In this study, the phenotypic characterization of STEMI patients (n=15) and healthy individuals (n=19) was performed, using a target metabolomics approach. Plasma samples were analyzed by UPLC-MS/MS (ultra-high-performance liquid chromatography-tandem mass spectrometry) and FIA-MS (MS-based flow injection analysis). The goal was to identify novel plasma biomarkers and metabolic signatures underlying STEMI. Concentrations of phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, and biogenic amines were altered in STEMI patients in relation to healthy subjects. Also, after multivariate analysis, it was possible to identify alterations in the glycerophospholipids, alpha-linolenic acid, and sphingolipid metabolisms in STEMI patients.