Excitotoxic spinal damage induced by kainic acid impairs locomotion, alters nociception, and reduces CREB nuclear translocation.

Our previous in vitro studies showed that excitotoxicity evoked by glutamate analogue kainate (KA) significantly decreased the number of rat spinal neurons and triggered high release of glutamate leading to locomotor network block. Our current objective was to assess the role of CREB as a predictive marker of damage following chemically-induced spinal cord injury by using in vivo and in vitro models. Thus, in vivo excitotoxicity in Balb/c adult mice was induced by KA intraspinal injection, while in vitro spinal cord excitotoxicity was produced by bath-applied KA. KA application evoked significant neuronal loss, deterioration in hindlimb motor coordination and thermal allodynia. In addition, immunohistochemical analysis showed that KA application resulted in decreased number of CREB positive nuclei in the ventral horn and in dorsal layers III-IV. Our data suggests that excitotoxic-induced neuronal loss may be potentially predicted by altered CREB nuclear translocation.

Resveratrol evokes neuroprotective effects and improves foot stance following kainate-induced excitotoxic damage to the mouse spinal cord.

Excitotoxicity, characterized by over-activation of glutamate receptors, is a major contributor to spinal cord injury (SCI) pathophysiology, resulting in neuronal death and loss of locomotor function. In our previous in vitro studies, we showed that excitotoxicity induced by the glutamate analogue kainate (KA) leads to a significant reduction in the number of neurons, providing a model for SCI. Our current objective was to assess the neuroprotective role of resveratrol (RESV), a natural polyphenol, following KA-induced SCI. In vivo excitotoxicity was induced by intraspinal injection of KA immediately followed by RESV administration to Balb/C adult male mice. In neonatal mouse spinal cord preparations, excitotoxicity was transiently induced by bath-applied KA, either with or without RESV. KA administration resulted in a significant deterioration in hindlimb motor coordination and balance during locomotion, which was partially reverted by RESV. Additionally, RESV preserved neurons in both dorsal and ventral regions. Sirtuin 2 (SIRT2) immunoreactive signal was increased by RESV, while the selective SIRT1 inhibitor 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide (EX-527) attenuated RESV neuroprotective effects. These findings suggest that RESV attenuation of excitotoxic-induced neuronal loss and locomotor deficits is mediated, at least in part, through the activation of SIRT1, potentially involving SIRT2 as well. Indeed, our results highlight the potential use of RESV to enhance neuroprotective strategies for SCI.

On the deformability of additivated phosphatidylcholine liposomes: Molecular dynamic regimes and membrane elasticity.

Liposomes with enhanced elasticity have been proven to increase the efficiency of drug transport across the skin. The understanding of the background physicochemical processes driving the liposome viscoelastic properties is an essential feature for the design of effective formulations involving different lipids and additive molecules. In this work we use field-cycled nuclear magnetic resonance relaxometry to analyze both the mechanical properties of liposome membranes, and their relationship with the involved molecular dynamics. Different liposomal formulations were considered. We show a correlation between the molecular dynamical regime and mesoscopic physical parameters that define the expected deformability of the vesicles. Results strongly suggest that the purity of the used lipids may influence the elastic properties of the membranes in an appreciable way. Common features in the behaviour of the involved dynamic variables were identified by comparing formulations with surfactants of similar molecular weight.

Worldwide prevalence, genotype distribution and management of hepatitis C.

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma, resulting in major global public health concerns. The HCV infection is unevenly distributed worldwide, with variations in prevalence across and within countries. The studies on molecular epidemiology conducted in several countries provide an essential supplement for a comprehensive knowledge of HCV epidemiology, genotypes, and subtypes, along with providing information on the impact of current and earlier migratory flows. HCV is phylogenetically classified into 8 major genotypes and 57 subtypes. HCV genotype and subtype distribution differ according to geographic origin and transmission risk category. Unless people with HCV infection are detected and treated appropriately, the number of deaths due to the disease will continue to increase. In 2015, 1.75 million new viral infections were mostly due to unsafe healthcare procedures and drug use injections. In the same year, access to direct-acting antivirals was challenging and varied in developing and developed countries, affecting HCV cure rates based on their availability. The World Health Assembly, in 2016, approved a global strategy to achieve the elimination of the HCV public health threat by 2030 (by reducing new infections by 90% and deaths by 65%). Globally, countries are implementing policies and measures to eliminate HCV risk based on their distribution of genotypes and prevalence.

Antioxidant, anti-inflammatory and neuroprotective actions of resveratrol after experimental nervous system insults. Special focus on the molecular mechanisms involved.

After different types of acute central nervous system insults, including stroke, subarachnoid haemorrhage and traumatic brain and spinal cord injuries, secondary damage plays a central role in the induction of cell death, neurodegeneration and functional deficits. Interestingly, secondary cell death presents an attractive target for clinical intervention because the temporal lag between injury and cell loss provides a potential window for effective treatment. While primary injuries are the direct result of the precipitating insult, secondary damage involves the activation of pathological cascades through which endogenous factors can exacerbate initial tissue damage. Secondary processes, usually interactive and overlapping, include oxidative stress, neuroinflammation and dysregulation of autophagy, ultimately leading to cell death. Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and red wine, exerts a wide range of beneficial health effects. Within the central nervous system, in addition to its inherent free radical scavenging role, resveratrol increases endogenous cellular antioxidant defences thus modulating multiple synergistic pathways responsible for its antioxidant, anti-inflammatory and anti-apoptotic properties. During the last years, a growing body of in vitro and in vivo evidence has been built, indicating that resveratrol can induce a neuroprotective state and attenuate functional deficits when administered acutely after an experimental injury to the central nervous system. In this review, we summarize the most recent findings on the molecular pathways involved in the neuroprotective effects of this multi target polyphenol, and discuss its neuroprotective potential after brain or spinal cord injuries.

Intrathecal Administration of an Anti-nociceptive Non-CpG Oligodeoxynucleotide Reduces Glial Activation and Central Sensitization.

Inflammatory pain associates with spinal glial activation and central sensitization. Systemic administration of IMT504, a non-CpG oligodeoxynucleotide originally designed as an immunomodulator, exerts remarkable anti-allodynic effects in rats with complete Freund´s adjuvant (CFA)-induced hindpaw inflammation. However, the anti-nociceptive mechanisms of IMT504 remain unknown. Here we evaluated whether IMT504 blocks inflammatory pain-like behavior by modulation of spinal glia and central sensitization. The study was performed in Sprague Dawley rats with intraplantar CFA, and a single lumbosacral intrathecal (i.t.) administration of IMT504 or vehicle was chosen to address if changes in glial activation and spinal sensitization relate to the pain-like behavior reducing effects of the ODN. Naïve rats were also included. Von Frey and Randall-Selitto tests, respectively, exposed significant reductions in allodynia and mechanical hypersensitivity, lasting at least 24 h after i.t. IMT504. Analysis of electromyographic responses to electrical stimulation of C fibers showed progressive reductions in wind-up responses. Accordingly, IMT504 significantly downregulated spinal glial activation, as shown by reductions in the protein expression of glial fibrillary acidic protein, CD11b/c, Toll-like receptor 4 (TLR4) and the phosphorylated p65 subunit of NFκB, evaluated by immunohistochemistry and western blot. In vitro experiments using early post-natal cortical glial cultures provided further support to in vivo data and demonstrated IMT504 internalization into microglia and astrocytes. Altogether, our study provides new evidence on the central mechanisms of anti-nociception by IMT504 upon intrathecal application, and further supports its value as a novel anti-inflammatory ODN with actions upon glial cells and the TLR4/NFκB pathway. Intrathecal administration of the non-CpG ODN IMT504 fully blocks CFA-induced mechanical allodynia and hypersensitivity, in association with reduced spinal sensitization. Administration of the ODN also results in downregulated gliosis and reduced TLR4-NF-κB pathway activation. IMT504 uptake into astrocytes and microglia support the concept of direct modulation of CFA-induced glial activation.

Resveratrol exerts anti-oxidant and anti-inflammatory actions and prevents oxaliplatin-induced mechanical and thermal allodynia.

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a frequent and devastating side effect of cancer therapy. No preventive strategies are currently available. We investigated the use of resveratrol (RESV) in the prevention of CIPNP and evaluated key components of the antioxidant defense system and neuroinflammatory factors as possible mediators contributing to RESV actions. Male rats were injected with oxaliplatin (OXA) and received daily oral RESV. Paw mechanical and thermal allodynia, oxidative stress, antioxidant, pro-inflammatory and neuronal injury/activation markers were evaluated in the sciatic nerve (SN), lumbar dorsal root ganglia (DRG) and spinal cord (SC). OXA-injected animals developed mechanical and thermal allodynia, while those receiving OXA + RESV showed patterns of response similar to control animals. Higher TBARS levels and lower GSH/GSSG ratios were observed in the SN of animals receiving OXA. The mRNA levels of the transcription factor NFκB and the pro-inflammatory cytokine TNFα were found to be upregulated both in lumbar DRG and SC. In addition, the antioxidant enzymes NQO-1 and HO-1 and the neuronal injury marker ATF3 showed increased levels of expression in lumbar DRG. In the dorsal SC the neuronal activation marker c-fos and the transcription factor Nrf2, main regulator of antioxidant defenses, were found to be upregulated. RESV early and sustained administration prevented NFκB, TNFα, ATF3 and c-fos upregulation, while increasing the expression of Nrf2, NQO-1, HO-1 and the redox-sensitive deacetylase SIRT1. RESV treatment was also able to restore TBARS levels and GSH/GSSG ratio. Thus, RESV administration resulted in the upregulation of antioxidant mediators, suppression of pro-inflammatory parameters and prevention of OXA-induced mechanical and thermal allodynia.

Tumor de células gigantes (osteoclastoma) multicentrico, diagnóstico incidental de adenoma paratiroideo reporte de caso / Multicenter giant cell tumor (osteoclastoma), incidental diagnosis of parathyroid adenoma case report

Los tumores de células gigantes (TDG) llamados también osteoclastomas o tumores pardos cuando se hallan dentro la esfera endocrinológica, son uno de los tumores menos frecuentes, más controversial y menos predecible en su comportamiento. Se producen como consecuencia del exceso de la actividad osteoclastica, como ocurre en el caso del hiperparatiroidismo, mismo que es un desorden endocrino común, por lo general asintomático y diagnosticado por el hallazgo fortuito de hipercalcemia. El diagnóstico de los osteoclastomas suele ser un reto, el alto índice de sospecha es esencial y la biopsia es el estándar de oro para el diagnóstico. Presentamos el caso de un hombre de 42 años quien presentó fracturas patológicas de radio derecho y tibia izquierda, gammagrama óseo con Tc ­ 99m con múltiples lesiones óseas , hormona paratiroidea (PTH) elevada, hipercalcemia, gammagrama de paratiroides con MIBI con presencia de adenoma paratiroideo, la biopsia de las lesiones óseas con presencia de células gigantes multinucleadas correspondientes a osteoclastomas; se llevó a cabo paratiroidectomia y el examen histopatológico confirmó la presencia de un adenoma paratiroideo.

Giant cell tumors (TDG), also called osteoclastomas or brown tumors when they are within the endocrinological sphere, are one of the least frequent, most controversial and least predictable tumors in their behavior. They occur as a consequence of excess osteoclastic activity, as occurs in the case of hyperparathyroidism, which is a common endocrine disorder, generally asymptomatic and diagnosed by the fortuitous finding of hypercalcemia. Diagnosing osteoclastomas is usually challenging, the high index of suspicion is essential, and biopsy is the gold standard for diagnosis. We present the case of a 42-year-old man who presented pathological fractures of the right radius and left tibia, a bone scan with Tc-99m with multiple bone lesions, elevated parathyroid hormone (PTH), hypercalcemia, parathyroid scan with MIBI with the presence of parathyroid adenoma, the biopsy of the bone lesions with the presence of multinucleated giant cells corresponding to osteoclastomas; parathyroidectomy was performed and histopathological examination confirmed the presence of a parathyroid adenoma.

Estudio morfométrico del punto asterional y su relación con los senos venosos durales / Morphometric study of the asterional point and its relationship with the dural venous sinuses

INTRODUCCIÓN: la importancia de conocer las diferentes reparaciones anatómicas que involucran la parte ósea de la fosa posterior con estructuras neurovasculares, disminuye la incidencia de complicaciones relacionadas con su acceso dentro del procedimiento neuroquirúrgico. MATERIALES Y MÉTODOS: estudio descriptivo basado en la evaluación de 90 hemicráneas secas, del Museo de Anatomía de la Universidad Mayor de San Andrés. RESULTADOS: la prevalencia de asterión tipo I fue de 28.9%, mientras que la de tipo II fue de 71.1%. La prevalencia del número de venas emisarias fue: una vena 54.4%, dos venas 42.2% y tres venas 3.3%. Los promedios para las características morfométricas son los siguientes: de Asterion a protuberancia occipital externa de 68.8 mm, de Asterion a cresta suprameatal de 50.1 mm, de Asterion a vena emisaria de 54.1 mm, de Asterion a Vértice del proceso mastoideo de 54.1 mm y de asterion a plano horizontal de Francfort 14.6 mm. La ubicación del asterión en el seno transverso fue la siguiente: al mismo nivel del seno, 47.8% de los casos, en el codo en 13.3%, superior al seno 31.1% e inferior a este en el 7.8%. CONCLUSIONES: hay una diferencia en algunos resultados morfométricos del asterión con respecto a otros autores, lo que podría determinar una configuración craneal diferente para nuestra población. Esto debe considerarse para evitar complicaciones durante el período transoperatorio en una cirugía de fosa posterior. Estos resultados reflejan la necesidad de realizar un estudio con una población más grande para obtener resultados reales, estableciendo así parámetros de corte que nos permitirán tener nuestra propia bibliografía sobre cómo proceder en nuestra actividad quirúrgica.

INTRODUCTION: the importance of knowing the different anatomical repairs that involve the bony part of the posterior fossa with neurovascular structures, decreases the incidence of complications related to its access within the neurosurgical procedure. MATERIALS AND METHODS: descriptive study based on the evaluation of 90 dry hemicranial, from the Anatomy Museum of the Universidad Mayor de San Andrés. RESULTS: the prevalence of asterion type I was 28.9%, while that of type II was 71.1%. The prevalence of the number of emissary veins was: One vein 54.4%, Two veins 42.2% and Three veins 3.3%. The averages for morphometric characteristics are as follows: from Asterion to external occipital protuberance 68.8 mm, from Asterion to suprameatal crest 50.1 mm, from Asterion to emissary vein 54.1 mm, from Asterion to Vertex from the mastoid process 54.1 mm and from asterion to horizontal plane of Frankfurt 14.6 mm. The location of asterion in the transverse sinus was the following: at the same level of the sinus 47.8% of the cases, in the elbow in 13.3%, superior to the sinus 31.1% and inferior to this in the 7.8%. CONCLUSIONS: there is a difference in some morphometric results of the asterion with respect to other authors, which could determine a different cranial configuration for our population. This should be considered to avoid complications during the transoperative period in a posterior fossa surgery. These results reflect the need to carry out a study with a larger population, in order to have real results, thus establishing cutting parameters that will allow us to have our own bibliography on how to proceed in our surgical activity.

Oxygen generating biomaterial improves the function and efficacy of beta cells within a macroencapsulation device.

Tissue-engineered devices have the potential to significantly improve human health. A major impediment to the success of clinically scaled transplants, however, is insufficient oxygen transport, which leads to extensive cell death and dysfunction. To provide in situ supplementation of oxygen within a cellular implant, we developed a hydrolytically reactive oxygen generating material in the form of polydimethylsiloxane (PDMS) encapsulated solid calcium peroxide, termed OxySite. Herein, we demonstrate, for the first time, the successful implementation of this in situ oxygen-generating biomaterial to support elevated cellular function and efficacy of macroencapsulation devices for the treatment of type 1 diabetes. Under extreme hypoxic conditions, devices supplemented with OxySite exhibited substantially elevated beta cell and islet viability and function. Furthermore, the inclusion of OxySite within implanted macrodevices resulted in the significant improvement of graft efficacy and insulin production in a diabetic rodent model. Translating to human islets at elevated loading densities further validated the advantages of this material. This simple biomaterial-based approach for delivering a localized and controllable oxygen supply provides a broad and impactful platform for improving the therapeutic efficacy of cell-based approaches.

Excessive daytime somnolence is associated with hypoglycemia in adult Latinos with type 2 diabetes mellitus.

OBJECTIVE: This study aimed to determine the frequency of sleep disorders in hypoglycemic diabetic patients and possible relationships with scores of sleep disorders and restless legs syndrome in mestizo population in Guayaquil, Ecuador. METHODS: A multicenter, cross-sectional study conducted at an outpatient endocrinology clinic in urban and rural Ecuador regions, included 290 participants with type 2 diabetes mellitus with severe hypoglycemic episodes, completed, validated, and culturally adapted sleep questionnaires to assess daytime sleepiness, risk of sleep apnea and restless legs syndrome. Logistic regression analysis was conducted to identify factors associated with severe hypoglycemia. RESULTS: The prevalence of EDS was 56.8%, RLS prevalence of 46.2%, and 38.6% prevalence of high risk Berlin score. Multivariate logistic regression indicated hypoglycemic T2DM in the range of 56-75 years old were more likely to have high ESS (p 0.0001). CONCLUSION: A high prevalence of sleep disorders in diabetic Latinos living in Ecuador was evidenced. The presence of somnolence in patients older than 56 years and high HbA1c levels should alert the clinician for the occurrence of hypoglycemic episodes.

[Non alcoholic steatohepatitis (NASH)]. / Esteatohepatitis no alcohólica (EHNA).

In this review we show you all the advances in ethiology, epidemiology, phisiopatology, natural history, clinic aspects, treatment and complications of non alcoholic steatohepatitis.

Esteatohepatitis no alcohólica (EHNA) / Non alcoholic steatohepatitis (NASH)

En la presente revisión mostramos lo último sobre la etiología, epidemiología, fisiopatología, historia natural, cuadro clínico, tratamiento y complicaciones de la esteatohepatitis no alcohólica...

In this review we show you all the advances in ethiology, epidemiology, phisiopatology, natural history, clinic aspects, treatment and complications of non alcoholic steatohepatitis...

Progesterone reduces the expression of spinal cyclooxygenase-2 and inducible nitric oxide synthase and prevents allodynia in a rat model of central neuropathic pain.

BACKGROUND: Spinal cord injury (SCI) results in the development of chronic pain that is refractory to conventional treatment. Progesterone, a neuroprotective steroid, may offer a promising perspective in pain modulation after central injury. Here, we explore the impact of progesterone administration on the post-injury inflammatory cascade involving the enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at the spinal cord level. We also analyse pain behaviours, the profile of glial cell activation, and IκB-α mRNA levels, as an index of NF-κB transactivation. METHODS: We used biochemical, immunohistochemical and molecular techniques, as well as behavioural studies, to investigate the effects of progesterone in a well-characterized model of central neuropathic pain. RESULTS: Injured animals receiving progesterone presented reduced mRNA levels of the proinflammatory enzymes, as well as decreased COX-2 activity and nitrite levels, as compared to vehicle-treated injured rats. Further, animals receiving the steroid exhibited lower levels of IκB-α mRNA, suggesting decreased NF-κB transactivation. Progesterone administration also attenuated the injury-induced increase in the number of glial fibrillary acidic protein and OX-42 positive cells both at early and late time points after injury, and prevented the development of mechanical and thermal allodynia. Further, when injured rats received early progesterone administration for a critical period of time after injury, they did not display allodynic behaviours even after the treatment had stopped. CONCLUSIONS: Our results suggest that progesterone, by modulating early neuroinflammatory events triggered after SCI, may represent a useful strategy to prevent the development of central chronic pain.

Tratamiento de las alopecias de patrón masculino y femenino. Eficacia clínica del aminexil y SP94 en dos series de 180 pacientes, hombres y mujeres / Treatment of alopecias of male and female patterns. Clinical efficacy of aminexil and SP94 in two surveys of 180 patients, men and women

El efecto del aminexil combinado con SP.94 fue evaluado como positivo en un grupo de pacientes de ambos sexos. Para poder confirmar estos positivos efectos se ha realizado un estudio en 180 pacientes de cada sexo en las Unidades de Tricología de dos Hospitales. Los pacientes se aplicaron sobre cuero cabelludo y cabellos húmedos 6 ml. de la loción todas las noches. A los pacientes se les realizó controles al comienzo del tratamiento y a los 45,90 y 180 días. Se efectuó en todos tipificación de la alopecia según las escalas de Ebling y Ludwig, y se les preguntó por su edad separándolos en grupos de menores de 17 años, entre 18 y 34 años, entre 35 y 49 años, y 50 o más años. También se interrogó por enfermedades y medicación concomitantes, presencia de dermatitis seborreica, cantidad de cabellos caídos en un lavado de 48 horas antes, deficiencias nutricionales o errores congénitos. A las mujeres con signos clínicos de síndrome SAHA se les realizó una analítica hormonal. La exploración del paciente en cada visita incluyó la realización de un tricograma con estudio del diámetro de los cabellos, signo de arrancamiento, sebometrías, corneometría, control iconográfico, graduación de la alopecia, y una valoración de la evolución de la dermatitis seborreica según una escala cuantitativa. En las visitas también se les pidió a los pacientes una valoración de la cosmeticidad y eficacia del producto, que de (..) (AU)

Effect of aminexil combined with SP94 was evaluated as positive in a group of patients of both genders. To confirm these positive effects a survey in 180patients of each gender has been performed in two Trichology Units of two Hospitals. Patients applied 6 ml. of the lotion in humid scalp all the nights. Controls to the start of treatment and at 45, 90, and 180 days was realized. Graduation of alopecia in accordance with the Ebling’s and Ludwig’s scales, and differentiation on four group of age (less than 17 year, between 18 and 34 years, between 35 and 49 years, and more than 50 year) was performed. All the patients were asked about their clinical background or treatments realized, seborrhoeic dermatitis, number of hairs shedding in a wash 48 hour before, nutritional deficiencies or congenital errors. Women with clinical signs of SAHA syndrome an hormonal analysis was performed Exploration of patients at each visit included trichogram and study of the hair diameter, pull sign, sebometry, corneometry, photographic control, graduation of alopecia, and a valoration of seborrhoeic dermatitis evolution in a quantitative scale. In each visit was also asked to patients for a evaluation about cosmeticity and efficacy of the lotion, by which of a subjecitive manner was divided in worst, similar, acceptable-better, and excellent, that was contrasted with the opinion of two physicians that had their evaluation based on the signs and photograph of each visit. Patient’s compliment was study with the Morisky-Green’s questionnaire. Patients that do not follow the protocol of application or that did not attend to some visit were substituted. Results permit to assure aminexil associated with SP.94 stop or delay loss of hair and favored its wide, although regroth of new hair lost in the evolutive process of androgenetic alopecia was not demonstrated, neither its actuation in seborrhorea and soborrhoeic dermatitis (AU)

Exposure assessment to ochratoxin A in Catalonia (Spain) based on the consumption of cereals, nuts, coffee, wine, and beer.

Ochratoxin A (OTA) was analysed in composite samples of cereal-based baby foods, beer, breakfast cereals (corn- and rice and wheat-based), loaf bread, peanuts and pistachios. Foodstuffs were collected in hypermarkets and supermarkets from 12 cities in the Spanish region of Catalonia, and composite samples were prepared for analysis involving liquid-liquid extraction, followed by immunoaffinity column clean-up and HPLC with fluorescence detection. Consumption data for the selected foodstuffs were collected by means of a food-frequency questionnaire. The studied population was grouped by age in infants, children, adolescents and adults; and exposure to OTA through the specified foodstuffs, and through wine and coffee, was assessed. Exposure assessment was done through deterministic and probabilistic modelling of the contamination and consumption data. OTA occurrence and mean of positive samples (ng g(-1) or ng ml(-1), for beer) were the following: 8.7% and 0.233 in baby foods; 88.7% and 0.022 in beer; 2.8% and 0.728 in corn-based breakfast cereals; 25% and 0.293 in wheat-based breakfast cereals; 12.9% and 0.283 in loaf bread; 41.7% and 0.241 in peanuts; and 2.9% and 0.228 in pistachios. The median estimated daily intake of OTA through the foodstuffs by each age group were below the latest provisional tolerable daily intakes (PTDIs) of 17 and 14 ng kg(-1) bw day(-1) recommended by the European Food Safety Authority (EFSA) in 2006 and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2007, respectively, ranging from 1% and 2% of those values in adolescents and children, to 3% and 11% in adults and infants.

Ochratoxin A in adult population of Lleida, Spain: presence in blood plasma and consumption in different regions and seasons.

Ochratoxin A (OTA) levels in blood plasma, as well as the consumption of possibly contaminated foodstuffs by adult inhabitants, were determined in three seasons in the plain and the mountain regions of the province of Lleida (Spain). Daily intake of the toxin was estimated in order to evaluate the exposure of the studied population. OTA was extracted from plasma through liquid-liquid extraction followed by immunoaffinity chromatography columns clean-up. Detection was done through HPLC-fluorescence, and limit of detection was 0.018ng/mL. Consumption data of the participants were obtained by means of a food frequency questionnaire. Occurrence of OTA in plasma was 100%. Range was 0.06-10.92ng/mL, and median was 0.50ng/mL. Differences between genders, regions or seasons were not significant, whereas significant differences were found among age groups. Regarding food consumption, significant differences were found between genders, but not between age groups, regions, or seasons. OTA plasma levels were not correlated with food consumption. Distributions of the intake estimations based on plasma levels differed from those based on food consumption and contamination. Mean and median values of the daily intake estimations were below the latest provisional tolerable daily intake of 14ng/kgbw/day, but some high percentiles were above it.

Sphinganine and sphingosine levels and ratio in urine and blood samples from a Catalonian population, Spain.

Fumonisins occur mainly in maize and they produce alterations on sphingolipid metabolism, unbalancing the sphinganine (Sa)/sphingosine (So) ratio. This alteration has been proposed as a biomarker of fumonisin exposure. The objective of this study was to establish the urinary and plasmatic levels of Sa, So as well as the ratio Sa/So from a sample of the Catalonian (Spain) population exposed to fumonisins at low levels. Firstly, plasma and urinary Sa and So levels and the ratio Sa/So were compared between two population groups, and later urinary Sa and So levels from corn food consumers and a control group were monitored for 2 weeks under controlled intake of corn foods. Sa and So levels were determined in urine and blood samples using validated methods using HPLC with fluorescence detection. Significant differences were not found in urine samples when Sa/So ratios were compared from corn food consumers and non-consumers, while significant differences were found in urine and plasma samples, but evidence of the mechanism of action of fumonisins was not apparent. Through a time-course study we have narrowed down the day in which the maximum alteration of Sa/So ratio should be expected in humans. This paper reports some useful information to improve the design of studies to validate the ratio Sa/So as a possible biomarker of fumonisin exposure.

Ochratoxin A and its metabolite ochratoxin alpha in urine and assessment of the exposure of inhabitants of Lleida, Spain.

Ochratoxin A (OTA) as well as its metabolite ochratoxin α (OTα) were detected in human urine in order to assess the exposure to OTA of a group of 72 adult inhabitants of the city of Lleida (Spain). Urine samples were enzymatically treated; OTA and OTα were separated by liquid-liquid extraction, and detected by HPLC-fluorescence. Exposure to OTA was also evaluated by the estimation of its daily intake from food contamination data from the literature and from food consumption data provided by the participants, who filled in a food frequency questionnaire (FFQ) and a three-day food consumption record (3DR). OTA occurrence (12.5%, limit of detection=0.034 ng/mL) was lower than OTα occurrence (61.1%, limit of detection=0.023 ng/mL). The range of concentrations was 0.057-0.562 ng/mL and 0.056-2.894 ng/mL for OTA and for OTα, respectively. It could be observed for positive samples that the FFQ data were related to the OTA concentration in urine, whereas the 3DR data were related to the OTα levels in urine. The OTA estimated daily intake of the participants was lower than 30% of the latest provisional tolerable daily intake of 14 ng/kg body weight/day in the worst cases of exposure.

Review. Ochratoxin A: presence in human plasma and intake estimation.

Ochratoxin A (OTA) is a fungal toxic secondary metabolite that can be found in several foodstuffs and thereby ingested by humans. One way to assess exposure of humans to OTA is the determination of the levels of this mycotoxin in blood plasma from a certain population. Such studies have been done in many countries, both in healthy people and nephropathy patients. Relationships with individual characteristics were investigated in several cases. Thus, most studies found no correlation with age, either with gender. However, the few studies that found correlation between OTA plasma levels and gender showed that men presented the highest values. When sampling was done over more than one season, the highest OTA plasma levels were found mostly in summer. Differences within regions of a country were related to dietary habits of each area. OTA levels of group populations showed variations from year to year, whereas intraindividual repetitions showed no specific trend. Daily intake of the toxin can be estimated from OTA plasma concentrations by the Klaassen equation. OTA toxicokinetics are considered in this review. Calculated daily intake of OTA by different studies did not overpass the proposed tolerable daily intakes of OTA.