LC-MS/MS-Based Profiling of Tryptophan-Related Metabolites in Healthy Plant Foods

Food plants contain hundreds of bioactive phytochemicals arising from different secondary metabolic pathways. Among these, the metabolic route of the amino acid Tryptophan yields a large number of plant natural products with chemically and pharmacologically diverse properties. We propose the identifier "indolome" to collect all metabolites in the Tryptophan pathway. In addition, Tryptophan-rich plant sources can be used as substrates for the fermentation by yeast strains to produce pharmacologically active metabolites, such as Melatonin. To pursue this technological development, we have developed a UHPLC-MS/MS method to monitor 14 Tryptophan, Tryptamine, amino-benzoic, and pyridine metabolites. In addition, different extraction procedures to improve the recovery of Tryptophan and its derivatives from the vegetal matrix were tested. We investigated soybeans, pumpkin seeds, sesame seeds, and spirulina because of their botanical diversity and documented healthy effects. Four different extractions with different solvents and temperatures were tested, and water extraction at room temperature was chosen as the most suitable procedure to extract the whole Tryptophan metabolites pattern (called by us "indolome") in terms of ease, high efficiency, short time, low cost, and sustainability. In all plant matrices, Tryptophan was the most abundant indole compound, while the pattern of its metabolites was different in the diverse plants extracts. Overall, 5-OH Tryptamine and Kynurenine were the most abundant compounds, despite being 100-1000-fold lower than Tryptophan. Melatonin was undetected in all extracts, but sesame showed the presence of a Melatonin isomer. The results of this study highlight the variability in the occurrence of indole compounds among diverse food plants. The knowledge of Tryptophan metabolism in plants represents a relevant issue for human health and nutrition

Empirical comparison of high gradient achievement for different metals in DC and pulsed mode

For the SwissFEL project, an advanced high gradient low emittance gun is under development. Reliable operation with an electric field, preferably above 125 MV/m at a 4 mm gap, in the presence of an UV laser beam, has to be achieved in a diode configuration in order to minimize the emittance dilution due to space charge effects. In the first phase, a DC breakdown test stand was used to test different metals with different preparation methods at voltages up to 100 kV. In addition high gradient stability tests were also carried out over several days in order to prove reliable spark-free operation with a minimum dark current. In the second phase, electrodes with selected materials were installed in the 250 ns FWHM, 500 kV electron gun and tested for high gradient breakdown and for quantum efficiency using an ultra-violet laser.Comment: 25 pages, 13 figures, 5 tables. Follow up from FEL 2008 conference (Geyongju Korea 2008) New Title in JVST A (2010) : Vacuum breakdown limit and quantum efficiency obtained for various technical metals using DC and pulsed voltage source

Can we improve the treatment of congestion in heart failure?

INTRODUCTION: Dyspnoea and peripheral oedema, caused by fluid redistribution to the lungs and/or by fluid overload, are the main causes of hospitalization in patients with heart failure and are associated with poor outcomes. Treatment of fluid overload should relieve symptoms and have a neutral or favorable effect on outcomes. AREAS COVERED: We first consider the results obtained with furosemide administration, which is still the mainstay of treatment of congestion in patients with heart failure. We then discuss important shortcomings of furosemide treatment, including the development of resistance and side effects (electrolyte abnormalities, neurohormonal activation, worsening renal function), as well as the relationship of furosemide - and its doses - with patient prognosis. Finally, the results obtained with potential alternatives to furosemide treatment, including different modalities of loop diuretic administration, combined diuretic therapy, dopamine, inotropic agents, ultrafiltration, natriuretic peptides, vasopressin and adenosine antagonists, are discussed. EXPERT OPINION: Relief of congestion is a major objective of heart failure treatment but therapy remains based on the administration of furosemide, an agent that is often not effective and is associated with poor outcomes. The results of the few controlled studies aimed at the assessment of new treatments to overcome resistance to furosemide and/or to protect the kidney from its untoward effects have been mostly neutral. Better treatment of congestion in heart failure remains a major unmet need

Medication Use and Costs Among Older Adults Aged 90 Years and Older in Italy

Older adults are often affected by multiple chronic conditions and experience geriatric syndromes that may affect the risk/benefit profile of medications. Little is known about the use of such medications in the older population. This article describes medication use and costs in Italian adults aged ≥90 years. Data from the 2019 Pharmaceutical Prescriptions database, concerning data on medications reimbursed by the Italian National Health Service, were analyzed in terms of prevalence and amount of use expressed as defined daily dose/1,000 users (DDD/1,000 users/day), accounting for different age-groups and sex. All individuals aged ≥90 years used at least one medication, with a mean number of 3128 DDD/1,000 users/day corresponding to an annual cost of 683 euros per user. Both use and costs linearly decreased with increasing age, with men accounting for a higher amount of DDD/1,000 users and costs than women across all age-groups. Antihypertensives (1330 DDD/1,000 inhabitants), antiplatelet agents (337 DDD/1,000 inhabitants), medications for peptic ulcer and gastroesophageal reflux (328 DDD/1,000 inhabitants), and lipid-lowering agents (166 DDD/1,000 inhabitants) were the most frequently used medications. We observed a progressive decrease in the usage of the majority of medications with increasing age, with the exception of antibiotics and antipsychotics. Individuals aged ≥90 years used a lower DDD/1,000 users, with an associated decrease in annual costs. The persistent use of preventive medications highlights the potential lack of awareness regarding medication rationalization and guidance for optimizing prescriptions. Our findings highlight the need for further initiatives to improve medications’ appropriateness in these older age-groups

On the Dynamics of the Deployment of Renewable Energy Production Capacities

This chapter falls within the context of modeling the deployment of renewable en-ergy production capacities in the scope of the energy transition. This problem is addressed from an energy point of view, i.e. the deployment of technologies is seen as an energy investment under the constraint that an initial budget of non-renewable energy is provided. Using the Energy Return on Energy Investment (ERoEI) characteristics of technologies, we propose MODERN, a discrete-time formalization of the deployment of renewable energy production capacities. Be-sides showing the influence of the ERoEI parameter, the model also underlines the potential benefits of designing control strategies for optimizing the deployment of production capacities, and the necessity to increase energy efficiency.Peer reviewe

Raised homocystein plasma concentration in patients with Heart Failure: clinical significance

Elevated plasma levels of homocysteine is associated with increased risk of thrombotic and atherosclerotic vascular disease. Several studies have demonstrated that hyperhomocysteinemia is an indipendent risk factor for vascular disease and is associated to heart failure. However there are no data regarding the association between homocysteine and various objective as well as subjective measures of heart failure. We hypothesized that plasma homocysteine is associated with clinical and echocardiographic signs of heart failure. On this ground we have analysed levels of homocysteine in patients with heart failure and possible correlation between these levels and clinical-functional pattern (NYHA class and ejection fraction). Methods: Plasma homocysteine levels were determined in 123 patients with dilated cardiomyopathy (59 males, 64 females, mean age 67±10 years, mean EF 31±11% and mean NYHA 2.4±0.9, 47 idiopatic and 76 postischemic cardiomyopathy) and 85 healthy control subjects (homogeneus group for sex and age). Patients with chronic renal failure, vitamin B12 and folate deficiency or factors affecting homocysteine plasma levels were escluded from this study. Homocysteine levels were determined in coded plasma samples by immunoenzimatic methods. Results: Patients with heart failure had a higher homocysteine level (mcg/L) than control subjects (21.72±10.28 vs 12.9±6.86, p<0,001) both postischemic (20.89±9.6 vs 12.9±6.86, p<0,001) and idiopatic cardiomiopathy (23.0±11.2 vs 12.9±6.86, p<0,001). A significant correlation was observed between homocysteine and NYHA functional class (p<0,001), age (p<0,001), creatinine (p<0,001), colesterol (p<0,05) while no correlations were observed with hemodynamic (HR, BP), functional (ejection fraction) and other metabolic parameters (triglycerides). Serum homocysteine was lowest in control and increased with increasing NYHA class. In idiopatic cardiomiopathy the correlation between homocysteine and NYHA functional class, creatinine (p<0,001), fibrinogen (p<0,05) was confirmed; in postischemic cardiomiopathy a significant correlation with creatinine and NYHA class (p<0,001) and with triglycerides (p<0,05) was also found. Conclusion: Plasma homocysteine was directly related to NYHA class. This observation may underline the strong relations of plasma homocysteine to congestive heart failure. Further research is indicated to evaluate a causal or noncausal mechanism for this association

Screening of new psychoactive substances (NPS)by gas-chromatography/time of flight mass spectrometry (GC/MS-TOF)and application to 63 cases of judicial seizure

A screening method for the separation and identification of more than fifty NPS is proposed. The method is based on fast gas-chromatography/time of flight mass spectrometry (FAST-GC/MS-TOF). Thanks to the shorter and narrower capillary column and to the rapid acquisition of the TOF detector a huge number of compounds are separated in a very short time of analysis (10 min). Only a few peaks were overlapped. The possibility to apply deconvolution by the software of the GC/MS-TOF instrument allowed the unequivocal identification also for the superimposed peaks. Linearity and LOD was studied and the method was applied to 63 cases of powders seized by the judicial authority at the airport of Milano Malpensa in Northern Italy in the period 2014\u20132017

Determination of polycyclic aromatic hydrocarbons in lipstick by gas-chromatography coupled to mass spectrometry: A case history

A suitable extraction protocol based on an liquid-liquid extraction with hexane/dimethyl sulfoxide and a GC/MS method were developed and validated to determine the concentration of six prohibited Polycyclic Aromatic Hydrocarbons (PAHs; benzo[a]pyrene; dibenz[a,h]anthracene; benz[a]anthracene; benzo[j]fluoranthene; benzo[k]fluoranthene; chrysene) in lipsticks commissioned by a cosmetic company to a manufacturer. The lipsticks were produced in four different colors. Analyses confirmed the presence of benz[a]anthracene and chrysene only in two colors in a concentration of 9.3\u20139.4 ng/g. The concentration of PAHs was 250 times lower than what is considered a toxic level on the basis of what reported in the litaraure and guidances for cosmetic ingredients; therefore we could assume that the risk for consumer health was negligeble

Determination of fungal activity in modified wood by means of micro-calorimetry and determination of total esterase activity

Beech and pine wood blocks were treated with 1,3-dimethylol-4,5-dihydroxyethylen urea (DMDHEU) to increasing weight percent gains (WPG). The resistance of the treated specimens against Trametes versicolor and Coniophora puteana, determined as mass loss, increased with increasing WPG of DMDHEU. Metabolic activity of the fungi in the wood blocks was assessed as total esterase activity (TEA) based on the hydrolysis of fluorescein diacetate and as heat or energy production determined by isothermal micro-calorimetry. Both methods revealed that the fungal activity was related with the WPG and the mass loss caused by the fungi. Still, fungal activity was detected even in wood blocks of the highest WPG and showed that the treatment was not toxic to the fungi. Energy production showed a higher consistency with the mass loss after decay than TEA; higher mass loss was more stringently reflected by higher heat production rate. Heat production did not proceed linearly, possibly due to the inhibition of fungal activity by an excess of carbon dioxide