Binging from Food to Alcohol: A Sequential Interaction Between Binging Behaviors in Male Wistar Rats.

The development of excessive alcohol (ethanol) and/or highly palatable food self-administration is an essential task to elucidate the neurobiological mechanisms that underlie these behaviors. Previous work has highlighted that ethanol self-administration is modulated by both the induction of aversive states (i.e., stress or frustration) and by the concurrent availability of appetitive stimuli (e.g., food). In our protocol, rats are food deprived for three days until they reach 82%-85% of their ad libitum weight. After that, rats are exposed daily for 10 days to a brief binge or control eating experience with highly sugary and palatable food (i.e., the ingestion of 11.66 and 0.97 kcal/3 min, respectively), which is followed by a two-bottle-choice test (ethanol vs. water) in their home cages for 90 min. This model induces robust binge eating, which is followed by a selective increase in ethanol self-administration. Therefore, this protocol allows to study: a) behavioral and neurobiological factors related to binge eating, b) different stages of alcohol use, and c) interactions between the latter and other addictive-like behaviors, like binge eating.

Statistical Analysis of Toxicological Data of Victims of Traffic Accidents in Galicia (Spain).

Driving under the influence of alcohol or drugs is a very common behavior in our environment and a serious problem for public health. On the one hand, in 2016, 400,000 people died in the world in traffic accidents in which ethanol was involved. On the other hand, traffic accidents in which the use of drugs of abuse other than ethyl alcohol accounted for more than 160,000 deaths worldwide in 2017. The objective of this work is to carry out a review of the 710 cases of people who died in traffic accidents received at the forensic toxicology service of the Institute of Forensic Sciences of the University of Santiago de Compostela (Galicia-Spain) over a period of 10 years (2009-2019). We performed an observational study of period prevalence, in which the following data were collected: age, sex, year, and analytical results in plasma, in the case of being positive. The data collected was subjected to statistical treatment. Of the 710 cases analyzed, 123 correspond to pedestrians and 587 to occupants of vehicles or motorcycles. A total of 77.6% of the deceased were men. At least one psychotropic substance was found in the blood of almost 40% of the victims. The most frequently found substance was ethyl alcohol, which appeared in 231 cases, more frequently in males. The second place is occupied by benzodiazepines, which appeared in 43 cases, followed by cocaine, which was detected in 25 cases. Polydrug use was found in only 44 cases, with the association of ethanol and cocaine being the most commonly found, followed by that of ethanol and benzodiazepines. Only in 5 of the cases analyzed there were 3 or more substances present. With the data obtained in this study, it is shown that in traffic accidents, the finding of different toxic or medicinal substances is frequent. Ethyl alcohol continues to be very present in road accidents (most detected substance), with the great impact that this implies. Secondly, the presence of benzodiazepines stands out, and cocaine is the third most detected toxic in this study. These results allow to obtain a profile of the substances most frequently involved in traffic accidents. Despite the surveillance, control, and information campaigns that the Spanish Government regularly carries out, the results are far from satisfactory.

From binge eating to binge drinking: A new and robust paradigm for assessing binge ethanol self-administration in male rats.

Animal models of alcohol (ethanol) self-administration are crucial to dissect the neurobiological mechanisms underlying alcohol dependence, yet only a few of these induce pharmacologically relevant levels of alcohol consumption and rarely the alcohol self-administration co-occurs with other addictive behaviours. The present study aims to validate a novel model of voluntary ethanol consumption in male Wistar rats, in which ethanol access follows a binge eating experience. Over 10 sessions, Wistar rats were exposed to binge or control eating (i.e., the ingestion of 11.66 and 0.97 kcal/3 min, respectively, derived from a highly palatable food), immediately followed by two-bottle choice intake tests (2%, 6%, 10% or 14% w/w ethanol vs. water). Rats exposed to binge eating drank significantly more 6% or 10% (w/w) ethanol than control peers, reaching up to 6.3 gEtOH /kg. Rats stimulated with 2%, 6%, 10% or 14% ethanol after binge eating, but not those given those ethanol concentrations after control eating, exhibited significant within-group increases in ethanol drinking. This ethanol consumption was not altered by quinine adulteration (up to 0.1 g/L), and it was blocked by naltrexone (10 mg/kg), administered immediately before binge eating. Blood ethanol levels significantly correlated with ethanol consumption; and the more ethanol consumed, the greater the distance travelled in an open field test conducted after the two-bottle choice test. Altogether, this self-administration model seems a valid and robust alternative with remarkable potential for research on different stages of the alcohol addiction and, particularly, to assess interactions between alcohol consumption and others addictive-like behaviours.

Evaluation of conventional and non-conventional biomarkers of liver toxicity in greenhouse workers occupationally exposed to pesticides.

The liver plays a prominent role in maintenance of homeostasis and is the major organ for xenobiotic metabolism, including pesticides. Conventional liver function tests are widely used to assess hepatocellular and biliary system dysfunction by measuring serum levels of aminotransferases (ALT, AST) and cholestasis enzymes (alkaline phosphatase -ALP- and γ-glutamyl transferase -GGT-), respectively. Although these tests are not entirely specific for liver damage, their specificity increases when measured concurrently, but still have limited usefulness to predict early liver dysfunction. Hence, non-conventional biomarkers may have a better performance for the early detection of biochemical hepatotoxicity with a greater specificity and sensitivity. A cross-sectional study with a follow-up component was conducted on 175 greenhouse workers regularly exposed to pesticides under integrated production system, and 91 controls living in the same geographical area. All individuals were evaluated for conventional (ALT, AST, ALP, GGT) and non-conventional biomarkers of hepatotoxicity (ornithine transcarbamylase (-OTC-), Arginase-1 -ARG1- and glutathione S-transferase alpha -GSTα-) over two periods of the same crop season, one of high pesticide exposure and other of low exposure. A slight increase in AST was observed in greenhouse workers relative to controls, suggestive of subtle hepatocellular toxicity. Although ALP, ARG1 and GST-α levels were decreased in greenhouse workers, this might be related to a potential homeostatic mechanism that regulates their expression. Altogether, these findings do not represent unambiguous evidence of liver dysfunction (e.g., hepatocellular or biliary system impairment) but may be the result of the low-toxicity pesticides used by greenhouse workers.

Evaluation of Gonadal Alterations in a Population Environmentally Exposed to a Mixture of Endocrine Active Pesticides.

Although there are studies that show that some pesticides produce gonadal dysfunction and gonadal cancer in different animals, there are not many studiesregardinghumans. This study determined the prevalence and risk in humans of developing ovarian or testicular dysfunction or cancer in areas with distinct exposure to pesticides, which have endocrine disrupting properties. A population-based case-control study was carried out on humans living in ten health districts of Andalusia (Southern Spain) classified as areas of high or low environmental exposure to pesticides according to agronomic criteria. The study population included 5332 cases and 13,606 controls. Data were collected from computerized hospital records between 2000 and 2018.The risk of gonadal dysfunction or cancer was significantly higher in areas with higher use of pesticides in relation to those with lower use.

Adherence to Mediterranean diet and risk of prostate cancer.

In Europe, countries following the traditional Mediterranean Diet (MeDi), particularly Southern European countries, have lower prostate cancer (PCa) incidence and mortality compared to other European regions. In the present study, we investigated the association between the MeDi and the relative risk of PCa and tumor aggressiveness in a Spanish population. Among individual score components, it has been found that subjects with PCa were less likely to consume olive oil as the main culinary fat, vegetables, fruits and fish than those without. However, these differences were not statistically significative. A high intake of fruit, vegetables and cooked tomato sauce Mediterranean style (sofrito) was related to less PCa aggressiveness. Results showed that there are no differences in the score of adherence to the Mediterranean dietary patterns between cases and controls, with mean values of 8.37 ± 1.80 and 8.25 ± 2.48, respectively. However, MeDi was associated with lower PCa agressiveness according to Gleason score. Hence, relations between Mediterranean dietary patterns and PCa are still inconclusive and merit further investigations. Further large-scale studies are required to clarify the effect of MeDi on prostate health, in order to establish the role of this diet in the prevention of PCa.

Biomarkers of oxidative stress in blood of workers exposed to non-cholinesterase inhibiting pesticides.

In occupational settings workers are often exposed to pesticides at relatively high doses compared to environmental exposures. Long-term exposure to pesticides has been associated with numerous adverse health effects in epidemiological studies, and oxidative stress is often claimed as one of the underlying mechanisms. In fact, different pesticides have been reported to induce oxidative stress due to the generation of free radicals and/or alteration in antioxidant defense enzymes. The present study examined greenhouse workers regularly exposed to diverse pesticides under integrated production system, and a group of controls of the same geographic area without any chemical exposure. Two different periods of the same crop season were assessed, one of high exposure (with greater use of pesticides) and other of low exposure (in which a less use of these compounds was made). Non-specific biomarkers of oxidative stress, e.g. thiobarbituric acid reactive substances (TBARS), ferric reducing ability of serum (FRAS), total thiol groups (SHT), gamma-glutamyl transpeptidase (GGT) and paraoxonase-1 (PON1) were measured in serum samples from all study subjects, alongside erythrocyte acetylcholinesterase (AChE). Results are suggestive of a mild increase in oxidative stress associated with pesticide exposure, which was compensated by an adaptive response to raise the antioxidant defenses and thus counter the detrimental effects of sustained oxidative stress. This response led to significantly increased levels of FRAS, SHT and PON1 in greenhouse workers relative to controls. Furthermore, AChE was decreased likely as a result of oxidative stress as workers did not use organophosphate insecticides.

Bioactive compounds of the Mediterranean diet and prostate cancer.

OBJECTIVE: The purpose of this review is to examine the evidence on the effects of bioactive constituents of the Mediterranean diet (MeDi) on prostate cancer (PCa) risk. METHODS: The search for articles came from extensive research in the following databases: PubMed, Scopus, and Web of Science. We used the search terms "Mediterranean diet," "lycopene," "vitamin E," "vitamin C," "Selenium," "resveratrol," "prostate cancer," and combinations, such as "lycopene and prostate cancer" or "resveratrol and prostate cancer." RESULTS: Numerous studies investigating the effect of various dietary nutrients on PCa have suggested that selenium is probably the most promising. Several studies reported reduced PCa risk associated with vitamin C and E intake, while other studies reported no association. Lycopene inhibits cell proliferation and inducts apoptosis, thus protecting against cancer. Also, it has been found in various in vivo and in vitro studies that resveratrol, inhibits PCa development. CONCLUSIONS: The high content of bioactive phytochemicals in the MeDi is of particular interest in the prevention of PCa. Further large-scale studies are required to clarify the effect of MeDi bioactive compounds on prostate health, in order to establish the role of this diet in the prevention of PCa.

Rapid determination of quetiapine in blood by gas chromatography-mass spectrometry. Application to post-mortem cases.

A simple, fast and sensitive method for the determination of quetiapine in human blood has been developed and validated. The method involved a basic liquid-liquid extraction procedure and subsequent analysis by gas chromatography-mass spectrometry, previous derivatization with bis(trimethylsilyl)-trifluoro-acetamide and chorotrimethylsilane (99 : 1). The methods of validation included linearity with a correlation coefficient > 0.99 over the range 0.02-1 µg ml(-1), intra- and interday precision (always < 12%) and accuracy (mean relative error always < 12%) to meet the bioanalytical acceptance criteria. The limit of detection was 0.005 µg ml(-1). The procedure was further applied to post mortems from the Institute of Legal Medicine, University of Santiago de Compostela.

Mediterranean diet adherence and prostate cancer risk.

BACKGROUND: Countries following the traditional Mediterranean Diet, particularly Southern European countries, have lower prostate cancer incidence and mortality compared to other European regions. The beneficial effect has been attributed to a specific eating pattern. OBJECTIVE: The purpose of this review is to examine the evidence to date on the effects of adherence to a Mediterranean Diet on prostate cancer risk; and to identify which elements of the Mediterranean diet are likely to protect against prostate cancer. METHODS: The search for articles came from extensive research in the following databases: PubMed, Scopus and Web of Science. We used the search terms "Mediterranean diet", "adherence", "fruit and vegetable", "olive oil", "fish" "legume", "cereal" "alcohol" "milk", "dairy product","prostate cancer", and combinations, such as "Mediterranean diet and prostate cancer" or "Olive oil and prostate cancer". RESULTS: There is strong evidence supporting associations between foods that are typical of a Mediterranean eating pattern and reduced prostate cancer risk. However, there are few studies that have assessed the effect of the Mediterranean diet on cancer prostate incidence. Recent data do not support associations to adherence to a Mediterranean Diet and risk of prostate cancer or disease progression. However, Mediterranean eating pattern after diagnosis of nonmetastatatic cancer was associated with lower overall mortality. CONCLUSION: Further large-scale studies are required to clarify the effect of Mediterranean diet on prostate health, in order to establish the role of this diet in the prevention of prostate cancer.

Introducción: Los países del sur de Europa, tienen una menor incidencia y mortalidad por cáncer de próstata en comparación con otras regiones europeas. Este efecto beneficioso se ha atribuido a un patrón de alimentación específica. Objetivo: El objetivo de esta revisión es examinar la evidencia sobre los efectos de la adhesión a la dieta mediterránea en el riesgo de cáncer de próstata; e identificar que componentes de la dieta mediterránea protegen contra el cáncer de próstata. Métodos: Se realizó una búsqueda en la literatura científica utilizando las siguientes base de datos: PubMed, Scopus and Web of Science. Utilizamos los términos de búsqueda "dieta mediterránea", "adhesión", "frutas y verduras", "aceite de oliva", "pescado" "legumbres", "cereal" "alcohol" "leche", "producto lácteo", "cáncer de próstata", y combinaciones, tales como"dieta mediterránea y cáncer de próstata "o" aceite de oliva y cáncer de próstata ". Resultados: Existe una fuerte evidencia que soporta una asociación entre alimentos que son típicos de un patrón de alimentación mediterránea y un menor riesgo de cáncer de próstata. Sin embargo, son pocos los estudios que han evaluado el efecto de la dieta mediterránea sobre la incidencia del cáncer de próstata. Los datos recientes no apoyan una asociación entre el seguimiento de este tipo de dieta y el riesgo de cáncer de próstata o su progresión. Sin embargo, un patrón de alimentación mediterránea después del diagnóstico de cáncer no metastásico se ha asociado con una disminución de la mortalidad global. Conclusión: Se requieren más estudios a gran escala para aclarar el efecto de la dieta mediterránea sobre la salud prostática, con el fin de establecer su papel en la prevención de cáncer de próstata.

Toxic effects of pesticide mixtures at a molecular level: their relevance to human health.

Pesticides almost always occur in mixtures with other ones. The toxicological effects of low-dose pesticide mixtures on the human health are largely unknown, although there are growing concerns about their safety. The combined toxicological effects of two or more components of a pesticide mixture can take one of three forms: independent, dose addition or interaction. Not all mixtures of pesticides with similar chemical structures produce additive effects; thus, if they act on multiple sites their mixtures may produce different toxic effects. The additive approach also fails when evaluating mixtures that involve a secondary chemical that changes the toxicokinetics of the pesticide as a result of its increased activation or decreased detoxification, which is followed by an enhanced or reduced toxicity, respectively. This review addresses a number of toxicological interactions of pesticide mixtures at a molecular level. Examples of such interactions include the postulated mechanisms for the potentiation of pyrethroid, carbaryl and triazine herbicides toxicity by organophosphates; how the toxicity of some organophosphates can be potentiated by other organophosphates or by previous exposure to organochlorines; the synergism between pyrethroid and carbamate compounds and the antagonism between triazine herbicides and prochloraz. Particular interactions are also addressed, such as those of pesticides acting as endocrine disruptors, the cumulative toxicity of organophosphates and organochlorines resulting in estrogenic effects and the promotion of organophosphate-induced delayed polyneuropathy.

Evaluation of pesticide-induced oxidative stress from a gene-environment interaction perspective.

Previously we reported that intensive agriculture workers exposed to pesticides had decreased levels of the intraerythrocyte enzymes delta-9-aminolevulinic acid dehydratase (ALA-D) and superoxide dismutase (SOD), very likely as a result of pesticide-induced oxidative stress. We have now examined in this population potential gene-environment interactions by modeling generalized estimating equations (GEE) adjusted for age, sex, body mass index and tobacco and alcohol consumption. Particularly, we assessed the interaction effects between plasma and erythrocyte cholinesterases (BChE and AChE, used as proxies for short- and long-term pesticide exposure, respectively) and a number of genetic polymorphisms of pesticide metabolizing enzymes such as paraoxonase-1 (PON1), glutathione-S-transferases (GST) and plasma cholinesterase variants (BCHE) on levels of erythrocyte antioxidant enzymes (SOD, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase and ALA-D). We observed significant interaction effects between BChE activity and PON1192R allele on catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase activities. BChE also interacted significantly with GSM1 null genotype on ALA-D and SOD. Regarding long-term pesticide exposure, a significant interaction was found between AChE and genotypes PON1192QR and PON1108CC on GR; between AChE and PON1192RR on SOD, and between AChE and GSTM1, GSTT1 and unusual BCHE variants on catalase activity. These findings suggest relevant gene-pesticide interactions and highlight the potential role of genetic risk factors in the pathomechanism of oxidative stress-induced degenerative diseases following pesticide exposure.

Biomonitorization of cadmium, chromium, manganese, nickel and lead in whole blood, urine, axillary hair and saliva in an occupationally exposed population.

Heavy metal contamination from occupational origin is a cause for concern because of its potential accumulation in the environment and in living organisms leading to long term toxic effects. This study was aimed to assess Cd, Cr, Mn, Ni and Pb levels in whole blood, urine, axillary hair and saliva from 178 individuals with occupational exposure to heavy metals. Levels of metal compounds were determined by atomic absorption spectrometry. We collected information on occupation, lifestyle habits and food intake by questionnaire. Multiple linear regression analyses for metal ion concentration in whole blood, urine, axillary hair and saliva were adjusted for age, gender, smoking and alcohol consumption, lifetime workplace exposure, residence area and food habits. Overall, blood and urine median concentrations found for the five metals analyzed do not exceed biological exposure indexes, so that they are very similar to a non-occupationally exposed population. Toxicokinetic differences may account for the lack of correlations found for metal levels in hair and saliva with those in blood or urine. For those heavy metals showing higher median levels in blood with respect to hair (Cd, Mn and Pb) indicating lesser hair incorporation from blood, the lifetime working experience was inversely correlated with their hair levels. The longer the lifetime working experience in industrial environments, the higher the Mn and Ni concentration in saliva. Axillary hair and saliva may be used as additional and/or alternative samples to blood or urine for biomonitoring hair Mn, and saliva Ni in subjects with occupational exposure.

Heavy metal concentrations in the general population of Andalusia, South of Spain: a comparison with the population within the area of influence of Aznalcóllar mine spill (SW Spain).

Levels of metalloids (As - urine) and heavy metals (Hg - urine, Cd - whole blood and Zn - serum) were determined by atomic absorption spectrometry in 601 subjects living in the area affected by the Aznalcóllar mine spill (SW, Spain) and compared with those of a representative sample (960 subjects) selected from the Andalusian community (non-affected area), southern Spain. The characteristic parameters of the analytical method including uncertainty were determined for each metal. Potential associations of metal concentration with age, sex and body mass index as well as life-style habits (smoking, alcohol consumption and food habits) were explored. Concentrations of all the metals studied were statistically higher in the population of the affected area with respect to that of the non-affected area in Andalusia, although levels were always lower or similar to the values reported for the general population and below occupational reference limits. In conclusion, there is a lack of evidence that the spill had any incidence on human health in the population living in the affected area. There are few references in scientific literature reporting values from large series of samples, and hence our data could be useful for further studies.