RESUMEN

Nutrient-dense, acceptable foods are needed in low-resource settings. Rice bran, a global staple byproduct of white rice processing, is rich in amino acids, fibers, and vitamins, when compared to other cereal brans. This pilot study examines the nutritional contribution of rice bran to the daily diets of mother-child pairs in rural southwest Guatemala. Thirty households were screened. Mothers (≥18 years) and children (6 to 24 months) completed 24 h dietary recalls at baseline and after 12 weeks (endline) for diet intake and diversity analyses. During biweekly visits for 12 weeks, households with <5 members received 14 packets containing 60 g of heat-stabilized rice bran, and those with ≥5 members received 28 packets. The macro- and micro-nutrient contributions of rice bran and whole, cooked black beans were included in dietary simulation models with average intakes established between the recalls and for comparison with dietary reference intakes (DRIs). A baseline child food frequency questionnaire was administered. The 27 mothers and 23 children with complete recalls were included in analyses. Daily maternal consumption of 10 g/d of rice bran plus 100 g/d of black beans resulted in all achieving at least 50% of the fiber, protein, magnesium, niacin, potassium, and thiamin DRIs. Daily child consumption of 3 g/d of rice bran plus 10 g/d of black beans resulted in all achieving at least 50% of the magnesium, niacin, phosphorous, and thiamine DRIs. For 15/17 food categories, male children had a higher intake frequency, notably for animal-source foods and coffee. Dietary rice bran coupled with black beans could improve nutritional adequacy, especially for fiber and key micro-nutrients, with broader implications for addressing maternal and child malnutrition in low-resource settings.

Asunto(s)

Niacina , Oryza , Femenino , Animales , Humanos , Masculino , Proyectos Piloto , Magnesio , Guatemala , Calor , Dieta , Vitaminas , Ingestión de Alimentos

RESUMEN

Introduction: Although there is an abnormal presentation of Niacin Response Syndrome (ANRS) in schizophrenic patients (SZ) compared to subjects with other psychiatric illnesses and with healthy individuals. However, most of the literature is based on studies that have used tests of niacin topical administration, observing, on the other hand, less scientific production of its oral administration. The objective was to determine the sensitivity of the oral niacin test as a method of detecting ASRN in EZ. Methods: A non-randomized clinical trial was carried out. Two groups were formed, the experimental or SZ, with 21 patients diagnosed with schizophrenia according to DSM-IV-TR SZ or schizoaffective disorder, and the HC group, made up of 20 healthy controls. Both groups were exposed to an oral niacin test and clinical-semiological tools were applied to evaluate the NRS. Results: 90.5% of the SZ group presented ANRS. In contrast, no participant in the HC group presented ANRS (0%). Conclusions: Oral niacin administration was sensitive to the detection of ASRN in schizophrenia. Likewise, ASRN could be a gradual phenomenon and its prevalence could be dose-dependent, being lower the lower the dose of oral niacin used. Further trials with larger and randomized samples will be needed.

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Introducción: En pacientes esquizofrénicos (EZ) existe un síndrome de respuesta a niacina (ASRN) anormal en comparación con sujetos con otras enfermedades psiquiátricas y con individuos sanos. Sin embargo, la mayor parte de la literatura se basa en estudios que han utilizado pruebas de niacina por vía tópica, observándose, en cambio, menor cantidad de ensayos utilizando su administración por vía oral, a pesar de existir algunas ventajas comparativas con el uso de esta última vía. El objetivo fue determinar la sensibilidad de la prueba de niacina por vía oral como método de detección del ASRN en EZ. Metodología: Se realizó un ensayo clínico no aleatorizado, conformando dos grupos, el grupo experimental o EZ, con 21 pacientes con diagnóstico de esquizofrenia según DSM-IV-TR SZ o trastorno esquizoafectivo, y el grupo CS, constituido por 20 controles sanos. Ambos grupos fueron expuestos a la prueba de niacina por vía oral y se aplicaron herramientas clínico-semiológicas para evaluar el SRN. Resultados: La prevalencia de ASRN fue del 90,5% en el grupo EZ, mientras que en el grupo CS fue nula (0%). Conclusiones: La administración oral de niacina fue sensible a la detección de ASRN en la esquizofrenia. Asimismo, la ASRN podría ser un fenómeno gradual y su prevalencia podría ser dosis-dependiente, siendo menor cuanto menor sea la dosis de niacina oral utilizada. Se necesitarán ensayos adicionales con muestras de mayor tamaño y aleatorizadas.

Asunto(s)

Niacina , Esquizofrenia , Humanos , Estudios Retrospectivos

RESUMEN

The objectives of this study were to estimate the residual and half-life of [imazapic + imazapyr] and to infer on the impact of these residuals over time. The first experiment comprised the application of [imazapic + imazapyr] to Clearfield® rice. On the following summer cropping season (365 days later), undeformed soil samples 0-5 cm depth were collected and seeds of six species or varieties were sown as bioindicators of residuals (experiment 2), being assessed plant height and dry mass 20 days after emergence start. The third experiment comprised the cultivation of the same species submitted to ten increasing herbicide doses (0-280 g ha-1) to establish standard response curves, also assessing plant height and dry mass 20 days after emergence start. About 2.1-5.8% of the applied imazapic remains in soil after one year, for the label doses. Imazapyr was considered to be at negligible doses as its half-life is short, and less than 0.0000001% of the applied dose is expected to be in soil 365 days later. The expected imazapic half-life in lowland areas of Southern Brazil is longer than for dryland, being estimated as between 63 and 77 days (95% confidence interval), contrasting to the 60 days half-life previously estimated for dryland soils.

Asunto(s)

Herbicidas , Niacina , Oryza , Contaminantes del Suelo , Brasil , Semivida , Herbicidas/análisis , Imidazoles , Niacina/análogos & derivados , Ácidos Nicotínicos , Suelo , Contaminantes del Suelo/análisis

RESUMEN

The present study aimed to evaluate the effect of applying different concentrations of niacin, at different times in relation to nitrogen fertilization, on the characteristics of Urochloa brizantha. The treatments consisted of applying three concentrations of niacin (0, 100, and 200 mg L-1) and three different moments (two days before, together, and two days after nitrogen fertilization). It was found that there was variation in response, mainly concerning the moment of application of the vitamins, in which the joint and subsequent application of fertilization generally exceeded the application performed previously, and of both concentrations used (100 and 200 mg L-1), in relation to the control without vitamin application. In this way, the application of niacin at a concentration of 100 mg L-1, carried out jointly or after nitrogen fertilization, provides better conditions for developing and producing dry matter of Urochloa brizantha due to the presence of nitrogen.

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O presente estudo teve como objetivo avaliar o efeito da aplicação de diferentes concentrações de niacina, em momentos distintos em relação à adubação nitrogenada, sobre as características de Urochloa brizantha. Os tratamentos foram compostos pela aplicação de três concentrações de niacina (0, 100 e 200 mg L-1) e três momentos distintos (dois dias antes, juntamente e dois dias após a adubação nitrogenada). Verificou-se que houve variação de resposta, principalmente em relação ao momento de aplicação das vitaminas, em que as aplicações conjunta e posterior à adubação superaram, de maneira geral, a aplicação realizada anteriormente, e de ambas as concentrações utilizadas (100 e 200 mg L-1), em relação ao controle sem vitamina. Desta maneira, a aplicação de niacina em concentração de 100 mg L-1, realizada de maneira conjunta ou posterior à adubação nitrogenada, propicia melhores condições para o desenvolvimento e a produção de matéria seca de Urochloa brizantha, devido à presença do nitrogênio.

Asunto(s)

Poaceae/química , Niacina/administración & dosificación , Nitrógeno/administración & dosificación , Niacinamida/administración & dosificación , Fertilizantes

RESUMEN

The number of people with dementia worldwide is estimated at 50 million by 2018 and continues to rise mainly due to increasing aging and population growth. Clinical impact of current interventions remains modest and all efforts aimed at the identification of new therapeutic approaches are therefore critical. Previously, we showed that JM-20, a dihydropyridine-benzodiazepine hybrid molecule, protected memory processes against scopolamine-induced cholinergic dysfunction. In order to gain further insight into the therapeutic potential of JM-20 on cognitive decline and Alzheimer's disease (AD) pathology, here we evaluated its neuroprotective effects after chronic aluminum chloride (AlCl3) administration to rats and assessed possible alterations in several types of episodic memory and associated pathological mechanisms. Oral administration of aluminum to rodents recapitulates several neuropathological alterations and cognitive impairment, being considered a convenient tool for testing the efficacy of new therapies for dementia. We used behavioral tasks to test spatial, emotional- associative and novel object recognition memory, as well as molecular, enzymatic and histological assays to evaluate selected biochemical parameters. Our study revealed that JM-20 prevented memory decline alongside the inhibition of AlCl3 -induced oxidative stress, increased AChE activity, TNF-α and pro-apoptotic proteins (like Bax, caspase-3, and 8) levels. JM-20 also protected against neuronal damage in the hippocampus and prefrontal cortex. Our findings expanded our understanding of the ability of JM-20 to preserve memory in rats under neurotoxic conditions and confirm its potential capacity to counteract cognitive impairment and etiological factors of AD by breaking the progression of key steps associated with neurodegeneration.

Asunto(s)

Cloruro de Aluminio/toxicidad , Benzodiazepinas/farmacología , Trastornos de la Memoria/inducido químicamente , Memoria/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Niacina/análogos & derivados , Cloruro de Aluminio/antagonistas & inhibidores , Animales , Hipocampo/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Prueba del Laberinto Acuático de Morris/efectos de los fármacos , Niacina/farmacología , Prueba de Campo Abierto/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Ratas , Ratas Wistar , Prueba de Desempeño de Rotación con Aceleración Constante

RESUMEN

Traumatic brain injury (TBI) is considered a public health problem and is often related to motor and cognitive disabilities, besides behavioral and emotional changes that may remain for the rest of the subject's life. Resident astrocytes and microglia are the first cell types to start the inflammatory cascades following TBI. It is widely known that continuous or excessive neuroinflammation may trigger many neuropathologies. Despite the large numbers of TBI cases, there is no effective pharmacological treatment available. This study aimed to investigate the effects of the new hybrid molecule 3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro1H-pyrido[2,3-b][1,5]benzodiazepine (JM-20) on TBI outcomes. Male Wistar rats were submitted to a weight drop model of mild TBI and treated with a single dose of JM-20 (8 mg/kg). Twenty-four hours after TBI, JM-20-treated animals showed improvements on locomotor and exploratory activities, and short-term memory deficits induced by TBI improved as well. Brain edema was present in TBI animals and the JM-20 treatment was able to prevent this change. JM-20 was also able to attenuate neuroinflammation cascades by preventing glial cells-microglia and astrocytes-from exacerbated activation, consequently reducing pro-inflammatory cytokine levels (TNF-α and IL-1ß). BDNF mRNA level was decreased 24 h after TBI because of neuroinflammation cascades; however, JM-20 restored the levels. JM-20 also increased GDNF and NGF levels. These results support the JM-20 neuroprotective role to treat mild TBI by reducing the initial damage and limiting long-term secondary degeneration after TBI.

Asunto(s)

Benzodiazepinas/farmacología , Conmoción Encefálica/metabolismo , Cognición/efectos de los fármacos , Factores de Crecimiento Nervioso/metabolismo , Neuroglía/efectos de los fármacos , Niacina/análogos & derivados , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Conducta Animal/efectos de los fármacos , Benzodiazepinas/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Modelos Animales de Enfermedad , Masculino , Microglía/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Niacina/farmacología , Niacina/uso terapéutico , Ratas , Ratas Wistar

RESUMEN

Coffee beans contain different volatile and non-volatile compounds that are responsible for their flavor and aroma. Herein, principal component analysis (PCA) was employed to correlate the non-volatile composition of specialty and traditional coffees with drink quality. The quantified non-volatile compounds included caffeine, chlorogenic acid, caffeic acid, and nicotinic acid in both types of coffee samples, while 5-hydroxymethylfurfural was only quantified in the specialty coffee samples. The most abundant compounds present in specialty coffees were associated with the aroma and flavor, affording a high drink quality. In traditional coffees, the most abundant compounds included nicotinic acid and caffeine, indicating a stronger roasting process, loss of sensory characteristics, and blended formulations. PCA showed a distinction between the traditional and specialty coffees such that a relationship between the contents of the compounds in each type of coffee, quality, and classification could be established.

Asunto(s)

Coffea/química , Café/química , Brasil , Ácidos Cafeicos/análisis , Cafeína/análisis , Cromatografía Líquida de Alta Presión , Coffea/metabolismo , Niacina/análisis , Análisis de Componente Principal

RESUMEN

This study evaluated the biological behavior of the coffee compounds Trigonelline (T), chlorogenic acid (C), and nicotinic acid (N), correlating with their release from a resin matrix. Minimum inhibitory concentration (MIC) was evaluated against Streptococcus mutans UA159, and cytotoxicity was assessed by methyl tetrazolium salt on OD-21 cells. Resin matrices (bisphenol A-glycidyl-dimethacrylate/triethylene glycol-dimethacrylate 70/30 wt%, camphorquinone/ethyl 4-dimethyl aminobenzoate 0.5/1 wt%) were doped with coffee compounds in different concentrations (10/20/30/40/50 wt%), performing 15 groups (T10-T50, C10-C50, N10-N50), and a control group with no coffee compound. Degree of conversion (DC%) was analyzed by Fourier transform infrared spectroscopy. Antimicrobial properties were evaluated by bioluminescence (Luciferase assay). The release from loaded matrices was analyzed over time (24 hr, 6, 14, 21 and 28 days), using high-performance liquid chromatography (HPLC). Data were submitted to ANOVA/Tukey's test (α = 0.05). MIC for T and C was 6 mg/ml, and 4 mg/ml for N. None of them were cytotoxic. Only T50 and C50 showed lower DC% than control (α < 0.05). Some groups (T30/T40/T50/C40/C50/N50) were strongly antimicrobial, reducing bacterial activity approximately five times compared to control (α < 0.05). For T30, T40, T50, C40, and C50, the HPLC showed a release above or closer to MIC values mainly in 24 hr, but for N50, up to 28 days. In conclusion, the coffee compounds presented antimicrobial activity, depending on their concentration when added in resin matrices, being found a correlation with their release.

Asunto(s)

Alcaloides , Antiinfecciosos , Ácido Clorogénico , Café/química , Niacina , Streptococcus mutans/crecimiento & desarrollo , Alcaloides/química , Alcaloides/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Ácido Clorogénico/química , Ácido Clorogénico/farmacología , Resinas Compuestas/química , Resinas Compuestas/farmacología , Niacina/química , Niacina/farmacología

RESUMEN

We have previously shown that JM-20, a new chemical entity consisting of 1,5-benzodiazepine fused to a dihydropyridine moiety, protects against rotenone-induced neurotoxicity in an experimental model of Parkinson's disease (PD). The aim of this study was to investigate the effect of a novel hybrid molecule, named JM-20, in in vitro and in vivo models of PD induced by 6-hydroxydopamine (6-OHDA). PC-12 cells were exposed to 6-OHDA and treated with JM-20. Protection against mitochondrial damage induced by 6-OHDA was also investigated using isolated rat brain mitochondria. We found that JM-20 protected PC-12 cells against cytotoxicity induced by 6-OHDA and inhibited hydrogen peroxide generation, mitochondrial swelling and membrane potential dissipation. For in vivo experiments, adult male Wistar rats were lesioned in the substantia nigra pars compacta (SNpc) by 6-OHDA administration. JM-20 was orally administered (10, 20 or 40 mg/kg), intragastric via gavage, 24 h after surgery and daily for seven days. Treatment with JM-20 significantly reduced the percentage of motor asymmetry and increased vertical exploration. It improved the redox state of the SNpc and the striatal tissue of these animals. Also, JM-20 reduced glial fibrillary acidic protein overexpression and increased tyrosine hydroxylase-positive cell number, both in SNpc. Altogether, these results demonstrate that JM-20 is a potential neuroprotective agent against 6-OHDA-induced damage in both in vitro and in vivo models. The mechanism underlying JM-20 neuroprotection against 6-OHDA appears to be associated with the control of oxidative injury and mitochondrial impairment.

Asunto(s)

Antioxidantes/farmacología , Benzodiazepinas/farmacología , Encéfalo/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Niacina/análogos & derivados , Oxidopamina/toxicidad , Trastornos Parkinsonianos/tratamiento farmacológico , Animales , Masculino , Mitocondrias/metabolismo , Niacina/farmacología , Prueba de Campo Abierto/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Células PC12/efectos de los fármacos , Trastornos Parkinsonianos/inducido químicamente , Ratas , Ratas Wistar

RESUMEN

Elevated plasma concentrations of the ketone body ß-hydroxybutyrate (BHB), an endogenous agonist of the hydroxycarboxylic acid receptor 2 (HCA2), is associated with an increased incidence of inflammatory diseases during lactation in dairy cows. In the early stages of this pathology, an increase in neutrophil recruitment is observed; however, the role of BHB remains elusive. This study characterized the effect of BHB and synthetic agonists of the HCA2 receptor on bovine neutrophil chemotaxis and the signaling pathways involved in this process. We demonstrated that treatment with BHB concentrations between 1.2 and 10 mM and two full selective agonists of the HCA2 receptor, MK-1903 and nicotinic acid, increased bovine neutrophil chemotaxis. We also observed that BHB and HCA2 agonists induced calcium release and phosphorylation of AKT, ERK 1/2 and AMPKα. To evaluate the role of these pathways in bovine neutrophil chemotaxis, we used the pharmacological inhibitors BAPTA-AM, pertussis toxin, U73122, LY294002, U0126 and compound C. Our results suggest that these pathways are required for HCA2 agonist-induced bovine neutrophil chemotaxis in non-physiological condition. Concentrations around 1.4 mM of BHB after calving may exert a chemoattractant effect that is key during the onset of the inflammatory process associated with metabolic disorders in dairy cows.

Asunto(s)

Ácido 3-Hidroxibutírico/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Quimiotaxis , Sistema de Señalización de MAP Quinasas , Neutrófilos/citología , Neutrófilos/enzimología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Animales , Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Bovinos , Quimiotaxis/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Niacina/farmacología , Fosforilación/efectos de los fármacos , Pirazoles/farmacología , Receptores Acoplados a Proteínas G/metabolismo , Fosfolipasas de Tipo C/metabolismo

RESUMEN

BACKGROUND: Maternal supplementation during lactation could increase milk B-vitamin concentrations, but little is known about the kinetics of milk vitamin responses. OBJECTIVES: We compared acute effects of maternal lipid-based nutrient supplement (LNS) consumption (n = 22 nutrients, 175%-212% of the RDA intake for the nutrients examined), as a single dose or at spaced intervals during 8 h, on milk concentrations and infant intake from milk of B-vitamins. METHODS: This randomized crossover trial in Quetzaltenango, Guatemala included 26 mother-infant dyads 4-6 mo postpartum who were randomly assigned to receive 3 treatments in a random order: bolus 30-g dose of LNS (Bolus); 3 × 10-g doses of LNS (Divided); and no LNS (Control), with control meals. Mothers attended three 8-h visits during which infant milk consumption was measured and milk samples were collected at every feed. Infant intake was assessed as $\mathop \sum \nolimits_{i\ = \ 1}^n ( {{\rm{milk\ volum}}{{\rm{e}}_{{\rm{feed\ }}n}} \times \ {\rm{nutrient\ concentratio}}{{\rm{n}}_{{\rm{feed}}\ n}}} )$ over 8 h. RESULTS: Maternal supplementation with the Bolus or Divided dose increased least-squares mean (95% CI) milk and infant intakes of riboflavin [milk: Bolus: 154.4 (138.2, 172.5) µg · min-1 · mL-1; Control: 84.5 (75.8, 94.3) µg · min-1 · mL-1; infant: Bolus: 64.5 (56.1, 74.3) µg; Control: 34.5 (30.0, 39.6) µg], thiamin [milk: Bolus: 10.9 (10.1, 11.7) µg · min-1 · mL-1; Control: 7.7 (7.2, 8.3) µg · min-1 · mL-1; infant: Bolus: 5.1 (4.4, 6.0) µg; Control: 3.4 (2.9, 4.0) µg], and pyridoxal [milk: Bolus: 90.5 (82.8, 98.9) µg · min-1 · mL-1; Control: 60.8 (55.8, 66.3) µg · min-1 · mL-1; infant: Bolus: 39.4 (33.5, 46.4) µg; Control: 25.0 (21.4, 29.2) µg] (all P < 0.001). Only the Bolus dose increased cobalamin in milk [Bolus: 0.054 (0.047, 0.061) µg · min-1 · mL-1; Control: 0.041 (0.035, 0.048) µg · min-1 · mL-1, P = 0.039] and infant cobalamin intake [Bolus: 0.023 (0.020, 0.027) µg; Control: 0.015 (0.013, 0.018) µg, P = 0.001] compared with Control. Niacin was unaffected. CONCLUSIONS: Maternal supplementation with LNS as a Bolus or Divided dose was similarly effective at increasing milk riboflavin, thiamin, and pyridoxal and infant intakes, whereas only the Bolus dose increased cobalamin. Niacin was unaffected in 8 h. This trial was registered at clinicaltrials.gov as NCT02464111.

Asunto(s)

Lactancia Materna , Lactancia , Micronutrientes/administración & dosificación , Micronutrientes/sangre , Vitaminas/administración & dosificación , Vitaminas/sangre , Adulto , Área Bajo la Curva , Estudios Cruzados , Suplementos Dietéticos , Femenino , Guatemala , Humanos , Lactante , Micronutrientes/química , Leche Humana/química , Niacina/administración & dosificación , Niacina/sangre , Niacina/farmacocinética , Piridoxal/administración & dosificación , Piridoxal/sangre , Piridoxal/farmacocinética , Riboflavina/administración & dosificación , Riboflavina/sangre , Riboflavina/farmacocinética , Tiamina/administración & dosificación , Tiamina/sangre , Tiamina/farmacocinética , Vitamina B 12/administración & dosificación , Vitamina B 12/sangre , Vitamina B 12/farmacocinética , Vitaminas/farmacocinética , Adulto Joven

RESUMEN

Once a significant cause of morbidity and mortality, health care providers rarely see primary pellagra in developed countries where fortification of foods with niacin is commonplace and niacin-rich foods are generally widely available. We report a ten-year-old boy with autism spectrum disorder who presented with photosensitive dermatitis which resolved after vitamin supplementation and dietary changes. In this child, the pellagra developed as the result of a long-term pattern of selective eating. Restricted diets, even to the point of nutrient deficiencies, are well-documented among children with autism spectrum disorders (ASD).

Asunto(s)

Trastorno del Espectro Autista , Trastorno Autístico , Niacina , Pelagra , Trastorno del Espectro Autista/complicaciones , Trastorno Autístico/complicaciones , Niño , Familia , Humanos , Masculino , Niacina/efectos adversos , Pelagra/complicaciones , Pelagra/diagnóstico , Pelagra/tratamiento farmacológico

RESUMEN

BACKGROUND: Detoxification of inorganic arsenic (iAs) occurs when it methylates to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Lower proportions of urinary iAs and MMA, and higher proportions of DMA indicate efficient methylation. The role of B-vitamins in iAs methylation in children with low-level arsenic exposure is understudied. OBJECTIVES: Our study objective was to assess the association between B-vitamin intake and iAs methylation in children with low-level arsenic exposure (<50 µg/L in water; urinary arsenic 5-50 µg/L). METHODS: We conducted a cross-sectional study in 290 ∼7-y-old children in Montevideo. Intake of thiamin, riboflavin, niacin, vitamin B-6, and vitamin B-12 was calculated by averaging 2 nonconsecutive 24-h recalls. Total urinary arsenic concentration was measured as the sum of urinary iAs, MMA, and DMA, and adjusted for urinary specific gravity; iAs methylation was measured as urinary percentage As, percentage MMA, and percentage DMA. Arsenic concentrations from household water sources were assessed. Linear regressions tested the relationships between individual energy-adjusted B-vitamins and iAs methylation. RESULTS: Median (range) arsenic concentrations in urine and water were 9.9 (2.2-48.7) and 0.45 (0.1-18.9) µg/L, respectively. The median (range) of urinary percentage iAs, percentage MMA, and percentage DMA was 10.6% (0.0-33.8), 9.7% (2.6-24.8), and 79.1% (58.5-95.4), respectively. The median (range) intake levels of thiamin, riboflavin, niacin, and vitamin B-6 were 0.81 (0.19-2.56), 1.0 (0.30-2.24), 8.6 (3.5-23.3), and 0.67 (0.25-1.73) mg/1000 kcal, respectively, whereas those of folate and vitamin B-12 were 216 (75-466) and 1.7 (0.34-8.3) µg/1000 kcal, respectively. Vitamin B-6 intake was inversely associated with urinary percentage MMA (ß = -1.60; 95% CI: -3.07, -0.15). No other statistically significant associations were observed. CONCLUSIONS: Although vitamin B-6 intake was inversely associated with urinary percentage MMA, our findings suggest limited support for a relation between B-vitamin intake and iAs methylation in children exposed to low-level arsenic.

Asunto(s)

Arsénico/metabolismo , Dieta , Exposición a Riesgos Ambientales , Vitamina B 6/administración & dosificación , Arsénico/análisis , Arsénico/orina , Arsenicales/orina , Ácido Cacodílico/orina , Niño , Estudios Transversales , Ingestión de Energía , Femenino , Humanos , Inactivación Metabólica/efectos de los fármacos , Masculino , Metilación , Niacina/administración & dosificación , Riboflavina/administración & dosificación , Tiamina/administración & dosificación , Uruguay , Vitamina B 12/administración & dosificación , Agua/química

RESUMEN

Humans and animals can be exposed to different chemical forms of mercury (Hg) in the environment. For example, methylmercury (MeHg)-contaminated fish is part of the basic diet of the riparian population in the Brazilian Amazon Basin, which leads to high total blood and plasma Hg levels in people living therein. Hg induces toxic effects mainly through oxidative stress. Different compounds have been used to prevent the damage caused by MeHg-induced reactive oxygen species (ROS). This study aims to investigate the in vivo effects of sub-chronic exposure to low MeHg levels on the mitochondrial oxidative status and to evaluate the niacin protective effect against MeHg-induced oxidative stress. For this purpose, Male Wistar rats were divided into four groups: control group, treated with drinking water on a daily basis; group exposed to MeHg at a dose of 100 µg/kg/day; group that received niacin at a dose of 50 mg/kg/day in drinking water, with drinking water being administered by gavage; group that received niacin at a dose of 50 mg/kg/day in drinking water as well as MeHg at a dose of 100 µg/kg/day. After 12 weeks, the rats, which weighed 500-550 g, were sacrificed, and their liver mitochondria were isolated by standard differential centrifugation. Sub-chronic exposure to MeHg (100 µg/kg/day for 12 weeks) led to mitochondrial swelling (p < 0.05) and induced ROS overproduction as determined by increased DFCH oxidation (p < 0.05), increased gluthatione oxidation (p < 0.05), and reduced protein thiol content (p < 0.05). In contrast, niacin supplementation inhibited oxidative stress, which counteracted and minimized the toxic MeHg effects on mitochondria.

Asunto(s)

Compuestos de Metilmercurio/toxicidad , Mitocondrias Hepáticas/efectos de los fármacos , Niacina/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Masculino , Compuestos de Metilmercurio/administración & dosificación , Mitocondrias Hepáticas/patología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

The main function of AChE is the hydrolysis of the neurotransmitter acetylcholine (ACh) at the neuromuscular and in cholinergic brain synapses. In some pathologies, loss of cholinergic neurons may be associated with a deficiency of ACh in specific brain areas. Consequently, the study of new safe drugs that inhibit AChE is important, because they can increase ACh levels in the synaptic cleft without adverse effects. Here, we evaluated the effects of JM-20 (a benzodiazepine-dihydropyridine hybrid molecule) on cholinesterase (ChE) activities from distinct sources (AChE from Electrophorus electricus (EeAChE), human erythrocyte membranes (HsAChE (ghost)), total erythrocyte (HsAChE (erythrocyte)) and BChE from plasma (HsBChE) and purified enzyme from the horse (EcBChE)). Kinetic parameters were determined in the presence of 0.05-1.6 mM of substrate concentration. The interactions ChEs with JM-20 were performed using molecular docking simulations. JM-20 inhibited all tested AChE but not BChE. The IC50 values were 123 nM ± 0.2 (EeAChE), 158 nM ± 0.1 (ghost HsAChE), and 172 nM ± 0.2 (erythrocytic HsAChE). JM-20 caused a mixed type of inhibition (it altered Km and Vmax of AChE). The molecular docking indicated the binding poses and the most plausible active isomer of JM-20. Besides giving important data for future drug design, our results help us understand the mode of action of JM-20 as a specific inhibitor of AChE enzymes.

Asunto(s)

Acetilcolinesterasa/metabolismo , Benzodiazepinas/farmacología , Inhibidores de la Colinesterasa/farmacología , Niacina/análogos & derivados , Animales , Diseño de Fármacos , Electrophorus , Caballos , Humanos , Cinética , Niacina/farmacología

RESUMEN

OBJECTIVE: JM-20, a novel hybrid synthetic molecule, has been reported to have antioxidant, mitoprotective, anti-excitotoxic, anti-apoptotic and anti-inflammatory properties. However, the neuroprotective effect of JM-20 against memory impairment in preclinical AD-like models has not been analyzed. The aim of this study was to evaluate the potential neuroprotection of JM-20 that preserves essential memory process from cholinergic dysfunction and other molecular damages. METHODS: The effects of JM-20 on scopolamine (1 mg/kg)-induced cognitive disorders were studied. Male Wistar rats (220-230 g) were treated with JM-20 and/or scopolamine, and behavioral tasks were performed. The AChE activity, superoxide dismutase activity, catalase activity, MDA and T-SH level on brain tissue were determined by spectrophotometric methods. Mitochondrial functionality parameters were measured after behavioral tests. Histological analyses on hippocampus and prefrontal cortex were processed with hematoxylin and eosin, and neuronal and axonal damage were determined. RESULTS: The behavioral, biochemical and histopathological studies revealed that oral pre-treatment with JM-20 (8 mg/kg) significantly attenuated the scopolamine-induced memory deficits, mitochondrial malfunction, oxidative stress, and prevented AChE hyperactivity probably due to specific inhibition of AChE enzyme. It was also observed marked histological protection on hippocampal and prefrontal-cortex regions. CONCLUSIONS: The multimodal action of this molecule could mediate the memory protection here observed and suggest that it may modulate different pathological aspects of memory deficits associated with AD in humans.

Asunto(s)

Benzodiazepinas/farmacología , Inhibidores de la Colinesterasa/farmacología , Disfunción Cognitiva/tratamiento farmacológico , Memoria/efectos de los fármacos , Niacina/análogos & derivados , Nootrópicos/farmacología , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Masculino , Memoria/fisiología , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Niacina/farmacología , Distribución Aleatoria , Ratas Wistar , Escopolamina

RESUMEN

Stroke is frequently associated with severe neurological decline and mortality, and its incidence is expected to increase due to aging population. The only available pharmacological treatment for cerebral ischemia is thrombolysis, with narrow therapeutic windows. Efforts aimed to identify new therapeutics are crucial. In this study, we look into plausible molecular and cellular targets for JM-20, a new hybrid molecule, against ischemic stroke in vivo. Male Wistar rats were subjected to 90 min middle cerebral artery occlusion (MCAO) following 23 h of reperfusion. Animals treated with 8 mg/kg JM-20 (p.o., 1 h after reperfusion) showed minimal neurological impairment and lower GABA and IL-1ß levels in CSF when compared to damaged rats that received vehicle. Immunocontent of pro-survival, phosphorylated Akt protein decreased in the cortex after 24 h as result of the ischemic insult, accompanied by decreased number of NeuN+ cells in the peri-infarct cortex, cornu ammonis 1 (CA1) and dentate gyrus (DG) areas. Widespread reactive astrogliosis in both cortex and hippocampus (CA1, CA3, and DG areas) was observed 24 h post-ischemia. JM-20 prevented the activated Akt reduction, neuronal death, and astrocytes reactivity throughout the brain. Overall, the results reinforce the pharmacological potential of JM-20 as neuroprotective agent and provide important evidences about its molecular and cellular targets in this model of cerebral ischemia.

Asunto(s)

Astrocitos/patología , Benzodiazepinas/uso terapéutico , Infarto Encefálico/tratamiento farmacológico , Encéfalo/patología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología , Neuronas/patología , Niacina/análogos & derivados , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Benzodiazepinas/farmacología , Infarto Encefálico/líquido cefalorraquídeo , Infarto Encefálico/patología , Región CA3 Hipocampal/efectos de los fármacos , Región CA3 Hipocampal/metabolismo , Región CA3 Hipocampal/patología , Muerte Celular/efectos de los fármacos , Giro Dentado/efectos de los fármacos , Giro Dentado/metabolismo , Giro Dentado/patología , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/metabolismo , Gliosis/patología , Infarto de la Arteria Cerebral Media/líquido cefalorraquídeo , Interleucina-10/líquido cefalorraquídeo , Interleucina-1beta/líquido cefalorraquídeo , Masculino , Neuronas/efectos de los fármacos , Niacina/farmacología , Niacina/uso terapéutico , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Wistar , Resultado del Tratamiento , Ácido gamma-Aminobutírico/líquido cefalorraquídeo

RESUMEN

Oxidative stress and mitochondrial dysfunction are two pathophysiological factors often associated with the neurodegenerative process involved in Parkinson's disease (PD). The aim of this study was to investigate the effects of a novel hybrid molecule, named JM-20, in different in vitro and in vivo models of PD induced by rotenone. To perform in vitro studies, SHSY-5Y cells were exposed to rotenone and/or treated with JM-20. To perform in vivo studies male Wistar rats were intoxicated with rotenone (2.5 mg/kg) via intraperitoneal injection and/or treated with JM-20 (40 mg/kg) administered via oral (for 25 days, both treatment). Rats were evaluated for global motor activity by measurement of locomotor activity. In addition, the effects on mortality, general behavior and redox parameters were also investigated. JM-20 protected SHSY-5Y cells against rotenone-induced cytotoxicity, evidenced by a significant diminution of cell death. In in vivo studies, JM-20 prevented rotenone-induced vertical exploration and locomotion frequency reductions, moreover prevented body weight loss and mortality induced by rotenone. It also improved the redox state of rotenone-exposured animals by increasing superoxide dismutase and catalase activities, total tissue-SH levels and decreasing malondialdehyde concentrations. Finally, JM-20 inhibited spontaneous mitochondrial swelling and membrane potential dissipation in isolated rats brain mitochondria. These results demonstrate that JM-20 is a potential neuroprotective agent against rotenone-induced damage in both in vitro and in vivo models, resulting in reduced neuronal oxidative injury and protection of mitochondria from impairment.

Asunto(s)

Benzodiazepinas/farmacología , Fármacos Neuroprotectores/farmacología , Síndromes de Neurotoxicidad/prevención & control , Niacina/análogos & derivados , Rotenona/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Encéfalo/metabolismo , Catalasa/metabolismo , Muerte Celular/efectos de los fármacos , Células Cultivadas , Humanos , Masculino , Mitocondrias/metabolismo , Actividad Motora/efectos de los fármacos , Niacina/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratas , Superóxido Dismutasa/metabolismo

RESUMEN

BACKGROUND: Acetohydroxyacid synthase large subunit 1 (Ahasl1) is a multiallelic locus involved in herbicide resistance in sunflower. Ahasl1-1 and Ahasl1-4 alleles harbor different point mutations that lead to different amino acid substitutions (Ala205Val and Trp574Leu, respectively). The objectives of this work were to evaluate the effect of these alleles at the enzymatic and whole-plant levels, and to determine the dominance relationships for imazapyr and metsulfuron-methyl herbicides. RESULTS: Resistant near-isogenic lines showed significantly lower specific AHAS activity than susceptible near-isoline. However, kinetic studies indicated that mutations did not change AHAS pyruvate affinity. Dose-response for six near-isolines carrying different combinations of Ahasl1-1 and Ahasl1-4 alleles and two herbicides (imazapyr and metsulfuron-methyl) were evaluated at whole-plant and enzymatic levels. Ahasl1-1 allele conferred moderate resistance to imazapyr and low resistance to metsulfuron-methyl. Conversely, Ahasl1-4 allele endowed high levels of resistance for both herbicides. Dominance of resistance at whole-plant level showed a semi-dominant behavior among the alleles for both herbicides. CONCLUSION: Ahasl1-4 allele confers higher resistance levels than Ahasl1-1 when evaluated with imazapyr and metsulfuron-methyl. Dominance estimations suggested that both parental lines should carry a resistance trait when developing hybrids. © 2018 Society of Chemical Industry.

Asunto(s)

Acetolactato Sintasa/genética , Arilsulfonatos/farmacología , Helianthus/genética , Resistencia a los Herbicidas/genética , Herbicidas/farmacología , Imidazoles/farmacología , Niacina/análogos & derivados , Proteínas de Plantas/genética , Acetolactato Sintasa/metabolismo , Alelos , Helianthus/efectos de los fármacos , Helianthus/enzimología , Niacina/farmacología , Proteínas de Plantas/metabolismo

RESUMEN

BACKGROUND The current common practice when using urine as a biomarker for vitamin excretion is to use a 24-hour sample for analysis. Due to the difficulty involved in this process, we attempted to find an alternative solution through the use of a single first morning void. The aim of our study was to investigate if there is a correlation between the first morning single void and the 24-hour collections of urines for the urine metabolite of niacin, N-1-methylnicotinamide (N1MN), and to test the reliability of utilizing a method using first morning single void collections corrected with the concentration of urine creatinine. MATERIAL AND METHODS All urine samples were collected from 30 healthy adult volunteers over the age of 18 years: 20 females and 10 males. Samples were collected after discarding the first morning urine and collecting every other urine voided during the next 24 hours including the first morning urine of the day after in 2 separate vessels. We analyzed the concentration of N1MN by high performance liquid chromatography and the concentration of creatinine by a commercial kit by spectrophotometry. The B3 excretion was expressed as the ratio of N1MN to creatinine. RESULTS We found a significant correlation between the ratios of first morning single void and 24-hour urines. When comparing males and females, the ratio demonstrated a significant correlation as well. CONCLUSIONS Our results demonstrated that it is possible to substitute a 24-hour collection with a first morning single void urine for the estimation of N1MN excretion.

Asunto(s)

Biomarcadores/orina , Niacina/orina , Adulto , Cromatografía Líquida de Alta Presión , Creatinina/orina , Femenino , Voluntarios Sanos , Humanos , Masculino , Reproducibilidad de los Resultados