Human clusterin gene polymorphisms associated with substance use disorders / Asociación entre polimorfismos del gen humano de clusterina y trastornos por consumo de sustancias

Previous work revealed that the levels of cluster in in biological fluids are associated with loss of control over eating and with the duration and intensity of tobacco use in humans. In non-human primates, chronic cocaine upregulates clusterin gene expression in the nucleus accumbens, a key area in addiction. All these findings have led to suggest that clusterin could be associated with the presence of different kind of addictive behaviours. In this work possible associations between clusterin gene polymorphisms and drug use disorder were studied. Forty-four selected single nucleotide polymorphisms (SNPs) of the clusterin gene were studied in DNA samples from 499 subjects diagnosed of substance use disorder (addicted to alcohol, cocaine or both) and 500 control subjects. Genotyping was performed by using a multiplexing assay and data were analysed with logistic regression. Four SNPs(rs867231, rs867232, rs9331896 and rs11787077) were found significantly associated with the presence of substance use disorder. These associations further extend the hypothesis that clusterin could be a relevant protein in addiction

Estudios previos han encontrado una asociación entre los niveles de clusterina en fluidos biológicos y la pérdida de control sobre la ingesta, así como entre dichos niveles y la duración e intensidad del consumo de tabaco. Por otra parte, la administración crónica de cocaína a primates no humanos incrementa la expresión del gen de clusterina en el Núcleo Accumbens, una región cerebral clave en las adicciones. Estos antecedentes sugieren que la clusterina podría estar implicada en distintos tipos de trastornos adictivos. En este trabajo se han estudiado posibles asociaciones entre polimorfismos de un solo nucleótido (single nucleotide polymorphisms, SNP) del gen de clusterina y trastornos por consumo de sustancias (TCS). Se genotiparon 44 SNP en muestras de ADN procedentes de 499 sujetos diagnosticados de TCS (adictos al alcohol, cocaína o ambas drogas) y 500 sujetos control. Para la secuenciación y el genotipado se utilizó la plataforma Sequenom y el análisis estadístico de los resultados se realizó mediante regresión logística. Se detectó una asociación significativa entre 4 SNP (rs867231, rs867232, rs9331896 y rs11787077) y la presencia de TCS. Estos resultados apoyan la hipótesis de que clusterina es una proteína relevante en las adicciones

Effects of Mediterranean diet in patients with recurring colds and frequent complications

Introduction: In recent years, traditional diets enriched with fresh plant-based foods have been gradually abandoned, increasing the consumption of animal foods and highly processed food. The aim of this study was to assess the effects of a nutritional intervention with a Traditional Mediterranean Diet in patients with recurring colds (RC) and frequent inflammatory complications (IC). Methods: Prospective before-after comparison study of 63 girls and 65 boys aged 1-5 years were included over a year in the nutritional programme ‘Learning to eat from the Mediterranean’. We studied clinical and therapeutic variables and various anthropometric parameters. Results: All the studied indicators (number of catarrhal episodes CB, degree of intensity, emergency and hospital admissions) showed a positive and statistically significant evolution, evidenced from the first weeks of starting treatment, until the end of the year, after which 53.9% of patients had no CB, 25% had only one, and 16.4% had two episodes, compared to the 4.64 episodes on average in the previous year. Antibiotic use decreased by 87.4%, from 3.85 ± 1.27 times/patient/year to 0.49 ± 0.79 (p<0.001). Symptomatic treatment decreased by 56.7%, from 7.03 ± 2.76 to 3.05 ± 1.69 (p<0.001). The satisfaction of the families was very high. The Kidmed index, which assesses the quality of the Mediterranean Diet, increased from 7.8 to 10.9 points. Conclusion: The adoption of a Traditional Mediterranean Diet could be a major contribution to the improvement of patients with recurring colds and frequent inflammatory complications (AU)

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Desabastecimientos de medicamentos en un hospital de tercer nivel en España / Shortages in medicinal products in a tertiary care hospital in Spain

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Effects of Mediterranean diet in patients with recurring colds and frequent complications.

INTRODUCTION: In recent years, traditional diets enriched with fresh plant-based foods have been gradually abandoned, increasing the consumption of animal foods and highly processed food. The aim of this study was to assess the effects of a nutritional intervention with a Traditional Mediterranean Diet in patients with recurring colds (RC) and frequent inflammatory complications (IC). METHODS: Prospective before-after comparison study of 63 girls and 65 boys aged 1-5 years were included over a year in the nutritional programme "Learning to eat from the Mediterranean". We studied clinical and therapeutic variables and various anthropometric parameters. RESULTS: All the studied indicators (number of catarrhal episodes CB, degree of intensity, emergency and hospital admissions) showed a positive and statistically significant evolution, evidenced from the first weeks of starting treatment, until the end of the year, after which 53.9% of patients had no CB, 25% had only one, and 16.4% had two episodes, compared to the 4.64 episodes on average in the previous year. Antibiotic use decreased by 87.4%, from 3.85±1.27 times/patient/year to 0.49±0.79 (p<0.001). Symptomatic treatment decreased by 56.7%, from 7.03±2.76 to 3.05±1.69 (p<0.001). The satisfaction of the families was very high. The Kidmed index, which assesses the quality of the Mediterranean Diet, increased from 7.8 to 10.9 points. CONCLUSION: The adoption of a Traditional Mediterranean Diet could be a major contribution to the improvement of patients with recurring colds and frequent inflammatory complications.

Mediterranean diet and childhood asthma

BACKGROUND: The incidence of bronchial hyperreactivity has increased to one-third of the population in developed countries, which requires the adoption of preventive and therapeutic measures. The objective of the present study was to assess the effects of a traditional Mediterranean diet on patients diagnosed with childhood asthma and determine if there is a beneficial effect from this dietary intervention. METHODS: Prospective before-after comparison study of 50 girls and 54 boys aged 1-5 years, who were enrolled in the 1-year programme "Learning to Eat from the Mediterranean", designed to promote the adoption of a traditional Mediterranean diet. We studied the clinical and therapeutic variables and anthropometric measurements. RESULTS: All studied symptomatic indicators (number and intensity of asthmatic attack, infections and hospital admissions) showed a positive and statistically significant evolution of bronchial hyperreactivity from the first weeks of the intervention onwards. Throughout the treatment, 32.2% of patients remained free of crisis, 35.3% of the patients only had one attack throughout the year and 24.9% had two episodes, compared to 4.73 episodes on average in the previous year. The use of inhaled corticosteroids markedly decreased from 3.92 ± 1.61 to 1.11 ± 1.09 times per patient per year (P < 0.001) and that of inhaled bronchodilators decreased from 4.14 ± 1.61 to 1.12 ± 1.40 (P < 0.001). As a result, the families involved in the programme reported a high level of satisfaction. CONCLUSIONS: The adoption of a traditional Mediterranean diet could contribute significantly to the improvement of patients diagnosed with childhood asthma

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Mediterranean diet and childhood asthma.

BACKGROUND: The incidence of bronchial hyperreactivity has increased to one-third of the population in developed countries, which requires the adoption of preventive and therapeutic measures. The objective of the present study was to assess the effects of a traditional Mediterranean diet on patients diagnosed with childhood asthma and determine if there is a beneficial effect from this dietary intervention. METHODS: Prospective before-after comparison study of 50 girls and 54 boys aged 1-5 years, who were enrolled in the 1-year programme "Learning to Eat from the Mediterranean", designed to promote the adoption of a traditional Mediterranean diet. We studied the clinical and therapeutic variables and anthropometric measurements. RESULTS: All studied symptomatic indicators (number and intensity of asthmatic attack, infections and hospital admissions) showed a positive and statistically significant evolution of bronchial hyperreactivity from the first weeks of the intervention onwards. Throughout the treatment, 32.2% of patients remained free of crisis, 35.3% of the patients only had one attack throughout the year and 24.9% had two episodes, compared to 4.73 episodes on average in the previous year. The use of inhaled corticosteroids markedly decreased from 3.92 ± 1.61 to 1.11 ± 1.09 times per patient per year (P<0.001) and that of inhaled bronchodilators decreased from 4.14 ± 1.61 to 1.12 ± 1.40 (P<0.001). As a result, the families involved in the programme reported a high level of satisfaction. CONCLUSIONS: The adoption of a traditional Mediterranean diet could contribute significantly to the improvement of patients diagnosed with childhood asthma.

Intensive follow-up strategies improve outcomes in nonmetastatic colorectal cancer patients after curative surgery: a systematic review and meta-analysis.

BACKGROUND: A wide variety of follow-up strategies are used for patients with colorectal cancer (CRC) after curative surgery. The aim of this study is to review the evidence of the impact of different follow-up strategies in patients with nonmetastatic CRC after curative surgery, in relation to overall survival and other outcomes. PATIENTS AND METHODS: A systematic search of PubMed, EMBASE, SCOPUS and ISI Web of Knowledge up to June 2014 was carried out. Eligible studies were all randomized clinical trials comparing the effectiveness of different follow-up strategies after curative resection in nonmetastatic CRC. RESULTS: Eleven studies with n = 4055 participants were included in a meta-analysis. A significant improvement in overall survival was observed in patients with more intensive follow-up strategies [hazard ratio = 0.75; 95% confidence interval (CI) 0.66-0.86]. A higher probability of detection of asymptomatic recurrences [relative risk (RR) = 2.59; 95% CI 1.66-4.06], curative surgery attempted at recurrences (RR = 1.98; 95% CI 1.51-2.60), survival after recurrences (RR = 2.13; 95% CI 1.24-3.69), and a shorter time in detecting recurrences (mean difference = -5.23 months; 95% CI -9.58 to -0.88) was observed in the intervention group. There were no significant differences in the total tumor recurrences, nor in the mortality related to disease. CONCLUSION: Intensive follow-up strategies improve overall survival, increase the detection of asymptomatic recurrences and curative surgery attempted at recurrence, and are associated with a shorter time in detecting recurrences. This more intensive follow-up could not be associated with an improvement in cancer-specific survival nor with an increased detection of total tumor recurrences. Follow-up with serum carcinoembryonic antigen and colonoscopies are related to an increase in overall survival.

Utilidad de la determinación de catecolaminas urinarias en el diagnóstico de un ganglioneuroblastoma / The use of urinary cathecolamine determination in diagnosing a ganglioneuroblastoma

El ganglioneuroblastoma es un tumor neuroblástico poco frecuente, que se produce casi exclusivamente en pacientes pediátricos. Más del 90% de los pacientes presentan niveles altos de catecolaminas y de sus metabolitos en orina. Presentamos el caso de un paciente de 4 años de edad, diagnosticado de un ganglioneuroblastoma, en el que la determinación de catecolaminas urinarias fue una importante herramienta para el diagnóstico debido a su sensibilidad, especificidad, rapidez y bajo coste(AU)

Ganglioneuroblastoma is a rare variety of neuroblastic tumor that occurs almost exclusively in pediatric patients. More than 90%of the patients present high levels of catecholamines and their metabolites in urine. We present the case of a four year-old patient who was diagnosed to have ganglioneuroblastoma, in which the determination of urinary catecholamines was an important tool for diagnosis due to their sensitivity, specificity, promptness and low cost(AU)

Undernutrition upregulates fumarate hydratase in the rat nucleus accumbens.

Previous comparative studies of fumarate hydratase (FH) protein density revealed that the enzyme was overexpressed in the striatum of rodents that are less influenced by rewarding stimuli, from cocaine to food. Therefore, we recently proposed FH as a potential striatal biomarker of brain reward deficiency and addiction vulnerability. This work has been focused to investigate FH activity in the Nucleus Accumbens (NAc) of undernourished rats, taking into account that malnutrition has been related to increased responsiveness to food and drug reward. To this end, we have studied adult female Wistar rats severely food restricted from the 16th day of intrauterine life until adulthood. Animals were sacrificed to dissect the NAc and obtain mitochondrial and cytosolic fractions after homogenisation and centrifugation. FH activity was measured by conversion of malate to fumarate, and protein levels were compared by Western blot analysis when fractions showed differences in activity. Undernutrition did not change cytosolic FH activity but led to a marked increase of mitochondrial FH activity (72 %) and protein content (50 %) in the NAc. This change was in the opposite direction that one would predict if it was related to addiction vulnerability of some kind, but strongly suggests that mitochondrial FH needs to be at some optimal level for normal reward responsiveness.

Implication of low level inflammation in the insulin resistance of adipose tissue at late pregnancy.

Insulin resistance is a characteristic of late pregnancy, and adipose tissue is one of the tissues that most actively contributes to the reduced maternal insulin sensitivity. There is evidence that pregnancy is a condition of moderate inflammation, although the physiological role of this low-grade inflammation remains unclear. The present study was designed to validate whether low-grade inflammation plays a role in the development of insulin resistance in adipose tissue during late pregnancy. To this end, we analyzed proinflammatory adipokines and kinases in lumbar adipose tissue of nonpregnant and late pregnant rats at d 18 and 20 of gestation. We found that circulating and tissue levels of adipokines, such as IL-1ß, plasminogen activator inhibitor-1, and TNF-α, were increased at late pregnancy, which correlated with insulin resistance. The observed increase in adipokines coincided with an enhanced activation of p38 MAPK in adipose tissue. Treatment of pregnant rats with the p38 MAPK inhibitor SB 202190 increased insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate-1 in adipose tissue, which was paralleled by a reduction of IR substrate-1 serine phosphorylation and an enhancement of the metabolic actions of insulin. These results indicate that activation of p38 MAPK in adipose tissue contributes to adipose tissue insulin resistance at late pregnancy. Furthermore, the results of the present study support the hypothesis that physiological low-grade inflammation in the maternal organism is relevant to the development of pregnancy-associated insulin resistance.

Hiperglicerolemia, una seudohipertrigliceridemia: A propósito de un niño de 6 años de edad / Hyperglycerolemia, a pseudo-hypertriglyceridemia: a case report

Las últimas recomendaciones del National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol In Adults (ATP III) consideran que un aumento de la concentración de triglicéridos en suero es un factor de riesgo independiente para la enfermedad coronaria. Los métodos de cuantificación no utilizan un «blanco de glicerol» y cuantifican este alcohol junto con la concentración de triglicéridos, por lo que una deficiencia de glicerol cinasa o una disminución de la capacidad de oxidación de glicerol pueden causar falsas elevaciones de triglicéridos. Se presenta el caso de un niño con falsa hipertrigliceridemia debido a glicerolemia (AU)

Recent recommendations from the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, considered that an increase in serum triglyceride levels is an independent risk factor for coronary heart disease. Most enzymatic methods used in routine laboratories do not involve a glycerol blank and determine both glycerol and triglycerides. Patients with glycerol-kinase deficiency or decreased ability to oxidize glycerol may be diagnosed with a pseudo-hypertriglyceridemia. We report a case of a child with a pseudo hypertriglyceridemia (falsely elevated triglycerides) due to a hyperglycerolemia (AU)

[Hyperglycerolemia, a pseudo-hypertriglyceridemia: a case report]. / Hiperglicerolemia, una seudohipertrigliceridemia: a propósito de un niño de 6 años de edad.

Recent recommendations from the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, considered that an increase in serum triglyceride levels is an independent risk factor for coronary heart disease. Most enzymatic methods used in routine laboratories do not involve a glycerol blank and determine both glycerol and triglycerides. Patients with glycerol-kinase deficiency or decreased ability to oxidize glycerol may be diagnosed with a pseudo-hypertriglyceridemia. We report a case of a child with a pseudo hypertriglyceridemia (falsely elevated triglycerides) due to a hyperglycerolemia.

Melanoma en glande. A propósito de un caso / Melanoma of the glans penis. Case report

Objetivo: Presentar un nuevo caso de melanoma localizado en el glande. Métodos/Resultados: Presentamos en este artículo el caso de un paciente diagnosticado y tratado en nuestro servicio, describiendo su forma de presentación así como su manejo terapéutico. Conclusiones: El melanoma de localización peneana es una forma infrecuente de presentación de este tipo de tumores cutáneos. Hacemos especial hincapié en su diagnóstico, presentación clínica y manejo terapéutico, ya que se trata de una neoplasia que requiere un diagnóstico y tratamiento precoces debido a su pronta diseminación metastásica (AU)

Objective: To report one case of melanoma of the glans penis. Methods/Results: We present the case of a patient diagnosed and treated in our department describing diagnosis and therapeutic management. Conclusions: Melanoma of the penis is an uncommon presentation form of this kind of cutaneous tumor. We especially emphasize its diagnosis, clinical presentation and therapeutic management due to its prompt metastatic dissemination requiring early diagnosis and treatment (AU)

Transient c-fos expression accompanies naturally occurring cell death in the developing interhemispheric cortex of the rat.

We have searched for the possible correlation of naturally occurring cell death with spontaneously enhanced c-fos expression in the developing cerebral cortex of normal Wistar albino rats. During the late prenatal and early postnatal period, cells with irregular contours and intracytoplasmic electron-dense granules (granule-containing cells) were apparent in the interhemispheric cortex, including the anterior cingulate and the retrosplenial cortices. These cells were loosely packed within the cortical layers derived from the cortical plate. Having excluded the possibility that these cells could be phagocytes by immunocytochemical experiments, we propose that they are cells in different phases of a process of autophagic degeneration and death. Images of extreme nuclear pyknosis were also apparent in identical locations. Cells showing immunoreactivity for c-Fos protein appeared in the same cortical areas. The immunoreactive cells were very abundant in the retrosplenial cortex, but were also present in the anterior cingulate cortex. These cells showed markedly irregular contours and large, densely immunoreactive intracytoplasmic inclusions; these images were similar to those of granule-containing cells revealed by conventional stains. The immunoreactivity for c-Fos protein was ephemeral, occurring exclusively during embryonic days 20 and 21, but granule-containing cells were observed for a longer period. The present results provide evidence, albeit indirect, that c-fos expression may occur in certain neural cells at the onset of a process of death by autophagia, and suggest a possible involvement of the proto-oncogene c-fos in certain forms of naturally occurring neuronal death.

Transient expression of c-fos during the development of the rat cerebral cortex.

The present study has explored with immunocytochemical methods the expression of the proto-oncogene c-fos during the pre- and postnatal development of the cerebral cortex of the rat. The immunostaining of the Fos protein follows a strikingly precise spatiotemporal pattern: it occurs uniquely within layer VIb of the developing cerebral cortex, and is transient, lasting only from embryonic day 20 until postnatal day 1. The expression of c-fos in layer VIb may be related to the dynamic changes that occur at this level during development.