Prevalence and risk factors associated with different comorbidities in obese children and adolescents.

INTRODUCTION: Different obesity-related comorbidities already present in childhood, such as: vitamin D deficiency, impaired carbohydrate metabolism, dyslipidaemia, arterial hypertension and non-alcoholic steatohepatitis. In this study, we aim to analyse the prevalence of comorbidities and to determine the predictive factors that affect these comorbidities. MATERIAL AND METHODS: Anthropometric, demographic and biochemical variables were collected from obese patients between six and 18 years of age. Subsequently, a statistical analysis was performed to describe the characteristics of the patients and the prevalence of comorbidities, as well as their predictive factors. RESULTS: A total of 158 obese children (76 boys and 82 girls) with a mean age at diagnosis of 12.48 years and a BMI Z-score of +3.24 SDS were included. The most prevalent comorbidities were vitamin D deficiency (64.2%), insulin resistance (45.1%), dyslipidaemia (32.2%), hyperuricaemia (18.5%) and arterial hypertension (15%). Age, BMI Z-score, percentage of fat mass and male sex have been found to be predictors of these comorbidities. CONCLUSION: Obese children and adolescents have a high prevalence of comorbidities. Once the diagnosis of obesity has been established, it would be very useful to identify early those patients with a higher risk of comorbidities, knowing their relationship with sex, age, BMI Z-score, percentage of fat mass and pubertal stage.

Design and implementation of an online tool for managing the availability of high-cost perishable medicines.

Introduction: Due to their impact on healthcare systems, the sustainability and optimization of high-cost drugs is an issue of concern for several countries. Different strategies have been implemented such as centralized purchasing to optimize budgetary resources. However, there is still a need for a mechanism to optimize these drugs further. Methods: We conducted this prospective multicenter intervention study in five hospitals in the Andalusian Public Health System of Cádiz (Spain) between July 2019 and September 2021. We developed an online website (Farmastock) and implemented it to determine the availability of high-cost, low-use, and near-expiry medicines in each hospital. We used a simple analysis using operational variables to assess the project intervention's savings impact on managing these high-cost drugs. Results: The implementation of Farmastock in Cádiz resulted in savings of 675,757.52 € for the Andalusian Public Health System, with 238 medicines transferred out of the 373 available. Of these medicines offered, the most considerable percentage were medicines used for pathologies with high clinical instability and accounted for nearly 80% of the medicines optimized by the tool. Conclusions: Farmastock allowed the Andalusian Public Health System to make substantial financial savings by not making new purchases of high-cost drugs available in other centers of this health network that were not being used. Therefore, this tool is a very efficient measure to contribute to the sustainability of the APHS and could be implemented in more hospitals soon.

Telomere-based risk models for the early diagnosis of clinically significant prostate cancer.

BACKGROUND: The objective of this study was to explore telomere-associated variables (TAV) as complementary biomarkers in the early diagnosis of prostate cancer (PCa), analyzing their application in risk models for significant PCa (Gleason score > 6). METHODS: As part of a larger prospective longitudinal study of patients with suspicion of PCa undergoing prostate biopsy according to clinical practice, a subgroup of patients (n = 401) with PSA 3-10 ng/ml and no prior biopsies was used to evaluate the contribution of TAV to discern non-significant PCa from significant PCa. The cohort was randomly split for training (2/3) and validation (1/3) of the models. High-throughput quantitative fluorescence in-situ hybridization was used to evaluate TAV in peripheral blood mononucleated cells. Models were generated following principal component analysis and random forest and their utility as risk predictors was evaluated by analyzing their predictive capacity and accuracy, summarized by ROC curves, and their clinical benefit with decision curves analysis. RESULTS: The median age of the patients was 63 years, with a median PSA of 5 ng/ml and a percentage of PCa diagnosis of 40.6% and significant PCa of 19.2%. Two TAV-based risk models were selected (TAV models 1 and 2) with an AUC ≥ 0.83 in the full study cohort, and AUC > 0.76 in the internal validation cohort. Both models showed an improvement in decision capacity when compared to the application of the PCPT-RC in the low-risk probabilities range. In the validation cohort, with TAV models 1 and 2, 33% /48% of biopsies would have been avoided losing 0/10.3% of significant PCa, respectively. The models were also tested and validated on an independent, retrospective, non contemporary cohort. CONCLUSIONS: Telomere analysis through TAV should be considered as a new risk-score biomarker with potential to increase the prediction capacity of significant PCa in patients with PSA between 3-10 ng/ml.

[Ultrasound-guided cryotherapy of small renal masses: Systematic review.] / Crioterapia renal guiada por ecografía para el tratamiento de masas renales de pequeño tamaño: revisión sistemática.

OBJECTIVE: Renal cryotherapy (RC) is an alternative therapeutic option to partial nephrectomy in elderly patients and/or patients with comorbidities. The technique can be guided by ultrasound, CT and MRI. Although CT is the most used technique, there are no comparative studies. The objective of this study was to review the current status of ultrasound as a guide for the planning and execution of RC. METHODS: A systematic review of the literature was carried out in the Pubmed/Medline database following the PRISMA guidelines. We used 42 articles that met the inclusion criteria for the synthesis of the evidence. RESULTS: Ultrasound allows dynamic and real-time monitoring of the entire procedure to guide the biopsy, placement of the cryoprobes, cryoball formation, and early identification of complications. The success rate and recurrences found in the percutaneous renal cryotherapy (PRC) were 97.04% and 1.81%, respectively, with 9.35% complications. The ultrasound during laparoscopic renal cryotherapy (LRC) has been shown to reduce the time spent in localizing the renal mass and also decreases the need for large dissections. On the other hand, contrast-enhanced ultrasound during follow-up shows a concordance with the CT or MRI of 72-96% and no complications have been described associated with its execution. CONCLUSION: Renal cryotherapy guided by ultrasound is a feasible technique, its main advantage is based on real-time monitoring during the procedure. The PRC presents an acceptable rate of complications and excellent oncological results. The LRC allows a rapid localization of the renal mass and reduces extensive dissections. During follow-up, the use of contrast ultrasound is a safe alternative that has been shown to have a good degree of agreement with respect to CT and MRI.

OBJETIVO: La crioterapia renal (CR) es una opción terapéutica alternativa a la nefrectomía parcial en pacientes de edad avanzada y/o comorbilidades. La técnica puede realizarse guiada por ecografía, TC y RM. Aunque la TC es la técnica mas utilizada, no existen estudios comparativos. El objetivo de este estudio fue revisar el estado actual de la ecografía como guía para la planificación y ejecución de la CR.MÉTODOS: Se llevó a cabo una revisión sistemática de la literatura en la base de datos Pubmed/Medline siguiendo las normas PRISMA. Se utilizaron 42 artículos que cumplieron los criterios de inclusión para la síntesis de la evidencia. RESULTADOS: La ecografía permite la monitorización dinámica y en tiempo real de todo el procedimiento permitiendo guiar la toma de biopsia, colocación de las criosondas, formación de la criobola, así como la identificación temprana de complicaciones. La tasa de éxito y recurrencias encontradas en la CR Percutánea (CRP) fue de 97,04% y 1,81%, respectivamente, con un 9,35 % de complicaciones. La ecografía en CR Laparoscópica (CRL) ha mostrado reducir el tiempo empleado en la localización de la masa renal e igualmente disminuye la necesidad de grandes disecciones. La ecografía con contraste durante el seguimiento muestra una concordancia con la TC o RMN de 72-96% y no se han descrito complicaciones asociadas a su ejecución.CONCLUSIÓN: La CR guiada por ecografía es una técnica factible cuya principal ventaja se basa en la monitorización a tiempo real durante el procedimiento. La CRP presenta tasa de complicaciones y resultados oncológicos aceptables. Mediante la CRL se puede realizar una localización rápida de la masa renal y reduce las disecciones extensas. Durante el seguimiento, el uso de la ecografía con contraste es una alternativa segura que ha mostrado tener buen grado de concordancia con respecto a la TC y la RMN.

Crioterapia renal guiada por ecografía para el tratamiento de masas renales de pequeño tamaño: revisión sistemática / Ultrasound-guided cryotherapy of small renal masses: Systematic review

Objetivo: La crioterapia renal (CR) es una opción terapéutica alternativa a la nefrectomía parcial en pacientes de edad avanzada y/o comorbilidades. La técnica puede realizarse guiada por ecografía, TC y RM. Aunque la TC es la técnica más utilizada, no existen estudios comparativos. El objetivo de este estudio fue revisar el estado actual de la ecografía como guía para la planificación y ejecución de la CR. Métodos: Se llevó a cabo una revisión sistemática de la literatura en la base de datos Pubmed/Medline siguiendo las normas PRISMA. Se utilizaron 42 artículos que cumplieron los criterios de inclusión para la síntesis de la evidencia. Resultados: La ecografía permite la monitorización dinámica y en tiempo real de todo el procedimiento permitiendo guiar la toma de biopsia, colocación de las criosondas, formación de la criobola, así como la identificación temprana de complicaciones. La tasa de éxito y recurrencias encontradas en la CR Percutánea (CRP) fue de 97,04% y 1,81%, respectivamente, con un 9,35 % de complicaciones. La ecografía en CR Laparoscópica (CRL) ha mostrado reducir el tiempo empleado en la localización de la masa renal e igualmente disminuye la necesidad de grandes disecciones. La ecografía con contraste durante el seguimiento muestra una concordancia con la TC o RMN de 72-96% y no se han descrito complicaciones asociadas a su ejecución. Conclusión: La CR guiada por ecografía es una técnica factible cuya principal ventaja se basa en la monitorización a tiempo real durante el procedimiento. La CRP presenta tasa de complicaciones y resultados oncológicos aceptables. Mediante la CRL se puede realizar una localización rápida de la masa renal y reduce las disecciones extensas. Durante el seguimiento, el uso de la ecografía con contraste es una alternativa segura que ha mostrado tener buen grado de concordancia con respecto a la TC y la RMN

Objective: Renal cryotherapy (RC) is an alternative therapeutic option to partial nephrectomy in elderly patients and/or patients with comorbidities. The technique can be guided by ultrasound, CT and MRI. Although CT is the most used technique, there are no comparative studies. The objective of this study was to review the current status of ultrasound as a guide for the planning and execution of RC. Methods: A systematic review of the literature was carried out in the Pubmed/Medline database following the PRISMA guidelines. We used 42 articles that met the inclusion criteria for the synthesis of the evidence. Results: Ultrasound allows dynamic and real-time monitoring of the entire procedure to guide the biopsy, placement of the cryoprobes, cryoball formation, and early identification of complications. The success rate and recurrences found in the percutaneous renal cryotherapy (PRC) were 97.04% and 1.81%, respectively, with 9.35% complications. The ultrasound during laparoscopic renal cryotherapy (LRC) has been shown to reduce the time spent in localizing the renal mass and also decreases the need for large dissections. On the other hand, contrast-enhanced ultrasound during follow-up shows a concordance with the CT or MRI of 72-96% and no complications have been described associated with its execution. Conclusion: Renal cryotherapy guided by ultrasound is a feasible technique, its main advantage is based on real-time monitoring during the procedure. The PRC presents an acceptable rate of complications and excellent oncological results. The LRC allows a rapid localization of the renal mass and reduces extensive dissections. During follow-up, the use of contrast ultrasound is a safe alternative that has been shown to have a good degree of agreement with respect to CT and MRI

Cytological and bacteriological sampling from filters used for embryo recovery to evaluate the uterine status of donor mares.

While testing for uterine bacterial infection is usually performed prior to artificial insemination (AI), samples taken during or after embryo flushing are generally not assessed either in subfertile and old mares or in fertile mares, even though knowledge of the status of the uterine environment in which the embryo is to develop would help to predict the outcome of embryo transfer programmes. The presence of bacteria and inflammatory cells in the liquid retained in the filter after uterine flushing in donors was determined at the moment of embryo recovery. Primarily, a group of mares (n = 8) displaying evident clinical signs of endometritis was selected to evaluate the cytological and bacteriological findings in filters after uterine flushing and in uterine cotton swabs. Two uterine samples (for cytological and bacterial evaluation) were taken with cotton swabs and, subsequently, the uterus was flushed and the efflux was also subjected to bacteriological and cytological analysis. Later, a group of donors (n = 20) was also involved to evaluate the presence of bacteria and polymorphonuclear leukocytes (PMN). After embryo flushing and collection, the efflux retained in the filter was evaluated by cytology and bacteriology. A sterile cotton swab was then scrubbed on the filter mesh, and a bacterial culture was performed. The embryo recovery rate was 30% (n = 6); Escherichia coli was isolated in one efflux sample collected from embryo-productive flushings, while the other five samples were negative by culture. Bacterial growth (not considered as contamination) was observed in a total of three samples, although no inflammatory cells were detected. Bacteria were isolated in endometrial samples collected after embryo flushing in donor mares, although inflammatory cells were never present in the uterus of mares from which embryos were recovered. In the absence of clinical signs, cytological and/or bacteriological samplings are not very useful for estimating the success of embryo recovery in donor mares, but evaluation of the filter and efflux after uterine flushing in donors may provide valuable information regarding uterine status at embryo collection.

Nitrosative deamination of 2'-deoxyguanosine and DNA by nitrite, and antinitrosating activity of ß-carboline alkaloids and antioxidants.

Endogenous and dietary nitrite produces reactive nitrogen species (RNS) that react with DNA causing mutations. The nitrosation of 2'-deoxyguanosine (dGuo) and DNA with nitrite was studied under different conditions, and the reaction and degradation products identified and analysed by HPLC-DAD-MS. Nitrosative deamination of dGuo produced xanthine along with 2'-deoxyxanthosine whereas DNA afforded xanthine. Formation of xanthine increased with nitrite concentration and in low pH such as that of stomach. Xanthine was measured as a marker of nitrosation of dGuo and DNA, and it was subsequently used to study the antinitrosating activity of ß-carboline alkaloids, and selected antioxidants. Food-occurring tetrahydro-ß-carbolines (THßCs) decreased nitrosative deamination of dGuo and DNA under conditions simulating the stomach. Antinitrosating activity was also evidenced for flavonoids (catechin, quercetin) and indole (melatonin) antioxidants. Among THßCs the most active antinitrosating compounds were 1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acids (THßC-3-COOHs) that reacted with nitrite to give N-nitroso derivatives as main products along with 3,4-dihydro-ß-carboline-3-carboxylic acids and aromatic ß-carbolines (norharman and harman). Antinitrosating activity of THßCs correlated well with the formation of N-nitroso-THßC-3-COOHs. These N-nitroso derivatives were stable at pH 7 but degraded in acid conditions affording nitrosating species.

Hydroxyl radical reactions and the radical scavenging activity of ß-carboline alkaloids.

ß-Carbolines are bioactive pyridoindole alkaloids occurring in foods, plants and the human body. Their activity as hydroxyl radical (OH) scavengers is reported here by using three different methods: deoxyribose degradation, hydroxylation of benzoate and hydroxylation of 2'-deoxyguanosine to give 8-hydroxy-2'-deoxyguanosine (8-OHdG) as assessed by RP-HPLC (MS). Fenton reactions (Fe(2+)/Fe(3+) plus H2O2) were used for OH generation, and the radical increased in the presence of ascorbic acid or 6-hydroxydopamine as pro-oxidants. ß-Carbolines were scavengers of OH in the three assays and in the presence of pro-oxidants. Tetrahydro-ß-carboline-3-carboxylic acids were active against the hydroxylation of 2'-deoxyguanosine. ß-Carbolines reacted with hydroxyl radicals (OH) affording hydroxy-ß-carbolines, whereas tetrahydro-ß-carbolines gave oxidative and degradation products. On the basis of IC50 and reaction rates (k), ß-carbolines (norharman and harman), and tetrahydro-ß-carbolines (tetrahydro-ß-carboline, 1-methyltetrahydro-ß-carboline and pinoline) were good OH radical scavengers and their activity was comparable to that of the indole, melatonin, which is an effective hydroxyl radical scavenger and antioxidant.

Naturally-occurring tetrahydro-ß-carboline alkaloids derived from tryptophan are oxidized to bioactive ß-carboline alkaloids by heme peroxidases.

ß-Carbolines are indole alkaloids that occur in plants, foods, and endogenously in mammals and humans, and which exhibit potent biological, psychopharmacological and toxicological activities. They form from naturally-occurring tetrahydro-ß-carboline alkaloids arising from tryptophan by still unknown way and mechanism. Results in this research show that heme peroxidases catalyzed the oxidation of tetrahydro-ß-carbolines (i.e. 1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid and 1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid) into aromatic ß-carbolines (i.e. norharman and harman, respectively). This oxidation followed a typical catalytic cycle of peroxidases through redox intermediates I, II, and ferric enzyme. Both, plant peroxidases (horseradish peroxidase, HRP) and mammalian peroxidases (myeloperoxidase, MPO and lactoperoxidase, LPO) catalyzed the oxidation in an efficient manner as determined by kinetic parameters (VMAX and KM). Oxidation of tetrahydro-ß-carbolines was inhibited by peroxidase inhibitors such as sodium azide, ascorbic acid, hydroxylamine and excess of H2O2. The formation of aromatic ß-carbolines by heme peroxidases can help to explain the presence and activity of these compounds in biological systems.

Metabolite profile resulting from the activation/inactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-methyltetrahydro-ß-carboline by oxidative enzymes.

Metabolic enzymes are involved in the activation/deactivation of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyiridine (MPTP) neurotoxin and its naturally occurring analogs 2-methyltetrahydro-ß-carbolines. The metabolic profile and biotransformation of these protoxins by three enzymes, monoamine oxidase (MAO), cytochrome P450, and heme peroxidases (myeloperoxidase and lactoperoxidase), were investigated and compared. The metabolite profile differed among the enzymes investigated. MAO and heme peroxidases activated these substances to toxic pyridinium and ß-carbolinium species. MAO catalyzed the oxidation of MPTP to 1-methyl-4-phenyl-2,3-dihydropyridinium cation (MPDP(+)), whereas heme peroxidases catalyzed the oxidation of MPDP(+) to 1-methyl-4-phenylpyridinium (MPP(+)) and of 2-methyltetrahydro-ß-carboline to 2-methyl-3,4-dihydro-ß-carbolinium cation (2-Me-3,4-DH ß C(+)). These substances were inactivated by cytochrome P450 2D6 through N-demethylation and aromatic hydroxylation (MPTP) and aromatic hydroxylation (2-methyltetrahydro-ß-carboline). In conclusion, the toxicological effects of these protoxins might result from a balance between the rate of their activation to toxic products (i.e., N-methylpyridinium-MPP(+) and MPDP(+)- and N-methyl--ß--carbolinium- ßC(+)-) by MAO and heme peroxidases and the rate of inactivation (i.e., N-demethylation, aromatic hydroxylation) by cytochrome P450 2D6.

Simultaneous generation of second to fifth harmonic conical beams in a two dimensional nonlinear photonic crystal.

Broadly tunable multiple high-harmonic conical beams have been generated by means of a multistep χ(2) cascade processes in a two dimensional nonlinear photonic crystal. The nonlinear structure consists of a square lattice of inverted hexagonal domains with diameters and distances between domains as low as 1 µm. The large number of reciprocal lattice vectors provided by both the square nonlinear structure and the hexagonal shaped domains, along with imperfections on the size and shape of the individual domains make possible the simultaneous generation of second up to fifth harmonic conical beams in a single nonlinear structure by using different types of phase matching geometries. The frequency response can be tuned in an extremely large spectral range, and continuous generation of nonlinear conical beams covering the whole visible spectral region can be achieved. Further, the same photon energy can be generated at different orders, so that concentrically emitted conical beams with angular dispersion as large as Δθ = 50° can be observed. The results highlight the significance of highly controlled engineered 2D nonlinear structures to generate advanced multi-photon devices with large spatial and spectral tunable response.

Synthesis and cytotoxic activity of a new potential DNA bisintercalator: 1,4-Bis{3-[N-(4-chlorobenzo[g]phthalazin-1-yl)aminopropyl]}piperazine.

The synthesis of new 1,4-bisalkylamino (2-4) and 1-alkylamino-4-chloro (5-6) substituted benzo[g]phthalazines is reported. Compounds 2-4 and 6 were prepared both in the free and heteroaromatic ring protonated forms. Bifunctional 6 contains the 1,4-bisaminopropylpiperazine chain as a linker between the two heteroaromatic units, whereas 5 is its monofunctional analogue. The in vitro antitumour activity of the synthesized compounds has been tested against human colon, breast and lung carcinoma cells, and also against human glioblastoma cells. Results obtained show that all of them are active in all cases, but bifunctional 6.2HCl is remarkably effective against the four cell lines tested, exhibiting IC50 values in the range of 10(-7) M, similar to those found for doxorubicin. The bifunctional structure of 6.2HCl enhances activity with respect to the monofunctional related compounds 5 and 7, leading to the highest activity among all the compounds tested. Molecular modelling of 6 suggests that those results could be indicative of DNA bisintercalation, which should be specially favoured in the diprotonated form 6.2HCl, a compound suitable for being studied more in depth in further biological tests. Measure of the DNA thermal melting curves show that the linear rise in Tm for bifunctional 6.2HCl is nearly twice than that one obtained for monofunctional 5, and supports the DNA-binding hypothesis.

N-methyltetrahydro-beta-carboline analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin are oxidized to neurotoxic beta-carbolinium cations by heme peroxidases.

2-Methyl-1,2,3,4-tetrahydro-beta-carboline (2-Me-THbetaC) and 2,9-dimethyl-1,2,3,4-tetrahydro-beta-carboline (2,9-diMe-THbetaC) are naturally occurring analogs of the Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), whereas their corresponding aromatic 2-methyl-beta-carbolinium cations resemble 1-methyl-4-phenylpyridinium (MPP(+)) and are considered potential toxins involved in Parkinson's disease (PD). To become toxicants, 2-methyltetrahydro-beta-carbolines need to be oxidized (aromatized) by human metabolic enzymes to pyridinium-like (beta-carbolinium) cations as occur with MPTP/MPP(+) model. In contrast to MPTP, human MAO-A or -B were not able to oxidize 2-Me-THbetaC to pyridinium-like cations. Neither, cytochrome P-450 2D6 or a mixture of six P450 enzymes carried out this oxidation in a significant manner. However, 2-Me-THbetaC and 2,9-diMe-THbetaC were efficiently oxidized by horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO) to 2-methyl-3,4-dihydro-beta-carbolinium cations (2-Me-DHbetaC(+), 2,9-diMe-DHbetaC(+)) as the main products, and detectable amount of 2-methyl-beta-carbolinium cations (2-Me-betaC(+), 2,9-diMe-betaC(+)). The apparent kinetic parameters (k(cat), k(4)) were similar for HRP and LPO and higher for MPO. Peroxidase inhibitors (hydroxylamine, sodium azide, and ascorbic acid) highly reduced or abolished this oxidation. Although MPTP was not oxidized by peroxidases; its intermediate metabolite 1-methyl-4-phenyl-2,3-dihydropyridinium cation (MPDP(+)) was efficiently oxidized to MPP(+) by heme peroxidases. It is concluded that heme peroxidases could be key catalysts responsible for the aromatization (bioactivation) of endogenous and naturally occurring N-methyltetrahydro-beta-carbolines and related protoxins to toxic pyridinium-like cations resembling MPP(+), suggesting a role for these enzymes in toxicological and neurotoxicological processes.

Endogenous and dietary indoles: a class of antioxidants and radical scavengers in the ABTS assay.

Indoles are very common in the body and diet and participate in many biochemical processes. A total of twenty-nine indoles and analogs were examined for their properties as antioxidants and radical scavengers against 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) ABTS*+ radical cation. With only a few exceptions, indoles reacted nonspecifically and quenched this radical at physiological pH affording ABTS. Indoleamines like tryptamine, serotonin and methoxytryptamine, neurohormones (melatonin), phytohormones (indoleacetic acid and indolepropionic acid), indoleamino acids like L-tryptophan and derivatives (N-acetyltryptophan, L-abrine, tryptophan ethyl ester), indolealcohols (tryptophol and indole-3-carbinol), short peptides containing tryptophan, and tetrahydro-beta-carboline (pyridoindole) alkaloids like the pineal gland compound pinoline, acted as radical scavengers and antioxidants in an ABTS assay-measuring total antioxidant activity. Their trolox equivalent antioxidant capacity (TEAC) values ranged from 0.66 to 3.9 mM, usually higher than that for Trolox and ascorbic acid (1 mM). The highest antioxidant values were determined for melatonin, 5-hydroxytryptophan, trp-trp and 5-methoxytryptamine. Active indole compounds were consumed during the reaction with ABTS*+ and some tetrahydropyrido indoles (e.g. harmaline and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid ethyl ester) afforded the corresponding fully aromatic beta-carbolines (pyridoindoles), that did not scavenge ABTS*+. Radical scavenger activity of indoles against ABTS*+ was higher at physiological pH than at low pH. These results point out to structural compounds with an indole moiety as a class of radical scavengers and antioxidants. This activity could be of biological significance given the physiological concentrations and body distribution of some indoles.

Tetrahydro-beta-carboline alkaloids occur in fruits and fruit juices. Activity as antioxidants and radical scavengers.

Tetrahydro-beta-carbolines are biologically active alkaloids that occur and accumulate in mammalian tissues, fluids, and brain, but their ultimate origin or biological role is still uncertain. Four tetrahydro-beta-carboline alkaloids: 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, 1-methyl-1,2,3,4-tetrahydro-beta-carboline, and 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline, are found as naturally occurring substances in some fruit and fruit juices. These compounds occur in the microg/g level in those products, and a characteristic and distinct profile appears to exist depending on the type of fruit and juice involved. Thus, 1-methyl-1,2,3,4-tetrahydro-beta-carboline may appear in tomato, tomato juice, and kiwi; 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline in bananas, pineapple, tomato, and their corresponding juices; and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in oranges and grapefruits, although it also occurred in most juices. Fruit-occurring tetrahydro-beta-carboline alkaloids acted as antioxidants and free radical scavengers in the ABTS assay when compared with ascorbic acid and Trolox. This suggests that tetrahydro-beta-carboline alkaloids might act as antioxidants when absorbed and accumulated in the body, contributing to the antioxidant effect of fruit products containing these compounds.

L-tryptophan reacts with naturally occurring and food-occurring phenolic aldehydes to give phenolic tetrahydro-beta-carboline alkaloids: activity as antioxidants and free radical scavengers.

The reaction between the essential amino acid l-tryptophan and flavoring or naturally occurring phenyl and phenolic aldehydes was studied, and the alkaloidal reaction products were characterized by NMR and HPLC-MS. Benzaldehyde, vanillin, syringaldehyde, salicylaldehyde, and anisaldehyde condensed with l-tryptophan in aqueous-acidic media affording the corresponding phenolic tetrahydro-beta-carboline-3-carboxylic acid as two diastereoisomers, 1S,3S-cis and 1R,3S-trans. With the exception of benzaldehyde, the rest of the aldehydes needed heating conditions (70 degrees C) to significantly form tetrahydro-beta-carbolines over time with the cyclization highly favored at low pH. This suggests a likely formation of these compounds under conditions that may occur in foods, food processing, or cooking. The new phenolic tetrahydro-beta-carboline alkaloids were assayed, for the first time, for their activity as free radical scavengers and antioxidants and showed good antioxidant properties with Trolox equivalent antioxidant capacity (TEAC) values much higher than those of ascorbic acid and the water soluble vitamin E analogue, Trolox, in the 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) assay.

Tetrahydro-beta-carboline alkaloids that occur in foods and biological systems act as radical scavengers and antioxidants in the ABTS assay.

Tetrahydro-beta-carboline alkaloids that occur in foods such as wine, seasonings, vinegar and fruit products juices, jams) acted as good radical scavengers (hydrogen- or electron donating) in the ABTS (2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) assay, and therefore, they could contribute to the beneficial antioxidant capacity attributed to foods. In contrast, the fully aromatic beta-carbolines norharman and harman did not show any radical scavenger activity in the same assay. During the reaction with ABTS.+ radical cation, tetrahydro-beta-carboline-3-carboxylic acid such as 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1,3-dicarboxylic acid (MTCA-COOH) were converted to harman, whereas 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (THCA) and 1,2,3,4-tetrahydro-beta-carboline-1,3-dicarboxylic acid (THCA-COOH) afforded norharman. These results suggest that food and naturally-occurring tetrahydro-beta-carboline alkaloids if accumulated in tissues, as reported elsewhere, might exhibit antioxidant activity.

Identification and occurrence of the novel alkaloid pentahydroxypentyl-tetrahydro-beta-carboline-3-carboxylic acid as a tryptophan glycoconjugate in fruit juices and jams.

The novel carbohydrate-derived beta-carboline, 1-pentahydroxypentyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, was identified in fruit- and vegetable-derived products such as juices, jams, and tomato sauces. This compound occurred as two diastereoisomers, a cis isomer (the major compound) and a trans isomer, ranging from undetectable amounts to 6.5 microg/g. Grape, tomato, pineapple, and tropical juices exhibited the highest amount of this alkaloid (up to 3.8 mg/L), whereas apple, banana, and peach juices showed very low or nondetectable levels. This tetrahydro-beta-carboline was also found in jams (up to 0.45 microg/g), and a relative high amount was present in tomato concentrate (6.5 microg/g) and sauce (up to 1.8 microg/g). This beta-carboline occurred in fruit-derived products as a glycoconjugate from a chemical condensation of D-glucose and L-tryptophan that is highly favored at low pH values and high temperature. Production, processing treatments, and storage of fruit juices and jams can then release this beta-carboline. Fruit-derived products and other foods containing this compound might be an exogenous dietary source of this glucose-derived tetrahydro-beta-carboline.