Social avoidance and altered hypothalamic-pituitary-adrenal axis in a mouse model of anxious depression: The role of LPA1 receptor.

Anxious depression is a prevalent disease with devastating consequences. Despite the lack of knowledge about the neurobiological basis of this subtype of depression, recently our group has identified a relationship between the LPA1 receptor, one of the six characterized G protein-coupled receptors (LPA1-6) for lysophosphatidic acid, with a mixed depressive-anxiety phenotype. Dysfunctional social behaviors, which have been related to increased activation of the hypothalamus-pituitary-adrenal (HPA) axis, are key symptoms of depression and are even more prominent in patients with comorbid anxiety and depressive disorders. Social behavior and HPA functioning were assessed in animals lacking the LPA1 receptor. For these purposes, we first examined social behaviors in wild-type and LPA1 receptor-null mice. In addition, a dexamethasone (DEX) suppression test was carried out. maLPA1-null mice exhibited social avoidance, a blunted response to DEX administration and an impaired circadian rhythm of corticosterone levels, which are features that are consistently dysregulated in many mental illnesses including anxious depression. Here, we have strengthened the previous experimental evidence for maLPA1-null mice to represent a good animal model of anxious depression, providing an opportunity to explore new therapeutic targets for the treatment of mood disorders, particularly this subtype of depression.

Erythrocyte micronucleus cytome assay in Passer domesticus and environmental remote sensing for inferring the quality of wild, rural, and urban areas.

The study of biomarkers in free-living birds can help to indicate the degree of contamination in distinct environments. In addition, these environments can be characterized through the information provided by satellite images. The objectives of the present study were to analyze the types and quantity of cytogenetic biomarkers in Passer domesticus (House sparrow) from three different environments, wild, rural, and urban, and to analyze them in the context of land use and anthropogenic actions. Five thousand erythrocytes per bird were analyzed for the following nuclear alterations (NA): micronuclei (MN), nuclear buds, notched nuclei, binucleated cells, nucleoplasmic bridges, nuclear tails, peripheral nuclei, and anucleated cells. In the study, wild birds exhibited five types of NA, seven types were found in rural birds, and all types were encountered in urban birds. The only NA that exceeded a frequency of 2 NA/1000 erythrocytes were peripheral nuclei in birds from the rural and urban sites, the latter environment characterized by 87% urban soil and air pollution. The highest frequencies of MN, peripheral nuclei, and anucleated erythrocytes were recorded in sparrows from the rural site (p ≤ 0.05). This area had been sprayed with chlorpyrifos 48%, the most widely used organophosphate in the region. Sparrows from the wild site, made up of 100% native forest, had higher frequencies of notched nuclei (p ≤ 0.05). A precedent is set for the use of environmental remote sensing in a complementary manner with cytogenetic biomarker studies in birds for a joint analysis in environmental assessment.

Bioactive pectic polysaccharides from bay tree pruning waste: Sequential subcritical water extraction and application in active food packaging.

The potential isolation of bio-active polysaccharides from bay tree pruning waste was studied using sequential subcritical water extraction using different time-temperature combinations. The extracted polysaccharides were highly enriched in pectins while preserving their high molecular mass (10-100 kDa), presenting ideal properties for its application as additive in food packaging. Pectin-enriched chitosan films were prepared, improving the optical properties (≥95% UV-light barrier capacity), antioxidant capacity (˃95% radical scavenging activity) and water vapor permeability (≤14 g·Pa-1·s-1·m-1·10-7) in comparison with neat chitosan-based films. Furthermore, the antimicrobial activity of chitosan was maintained in the hybrid films. Addition of 10% of pectins improved mechanical properties, increasing the Young's modulus 12%, and the stress resistance in 51%. The application of pectin-rich fractions from bay tree pruning waste as an additive in active food packaging applications, with triple action as antioxidant, barrier, and antimicrobial has been demonstrated.

Virus Zika: manifestaciones cutáneas en 3 pacientes / Zika Virus: Cutaneous Manifestations in 3 Patients

La infección por el virus Zika debe sospecharse en viajeros o inmigrantes con clínica de viriasis (exantema, fiebre, artralgias, artritis, conjuntivitis, cefalea, etc.) y una historia epidemiológica compatible. Aunque las manifestaciones cutáneas se encuentran entre las más frecuentes no son específicas y su iconografía es escasa. Presentamos 3 casos, 2 viajeros y un inmigrante que comienzan con un exantema por virus Zika. Alcanzar el diagnóstico de forma rápida optimiza el manejo de estos pacientes, mejora el control de los casos graves y permite minimizar una posible transmisión autóctona dado el riesgo que supone la presencia del Aedes albopictus como potencial vector transmisor de esta enfermedad en el litoral mediterráneo español

Zika virus infection should be suspected in travelers or immigrants with the signs or symptoms of a viral infection (rash, fever, joint pains, conjunctivitis, headache, etc.) and a compatible epidemiological history. Although cutaneous manifestations are among the most common clinical signs of Zika, they are not specific and very few images are available. We present 3 patients (2 travelers and 1 immigrant) in whom a rash was the presenting manifestation of Zika virus infection. Prompt diagnosis optimizes outcomes in these patients, improves the management of severe disease, and minimizes the risk of local transmission by Aedes albopictus, now a potential local vector for the virus due to its presence in areas along Spain's Mediterranean coast

Zika Virus: Cutaneous Manifestations in 3 Patients. / Virus Zika: manifestaciones cutáneas en 3 pacientes.

Zika virus infection should be suspected in travelers or immigrants with the signs or symptoms of a viral infection (rash, fever, joint pains, conjunctivitis, headache, etc.) and a compatible epidemiological history. Although cutaneous manifestations are among the most common clinical signs of Zika, they are not specific and very few images are available. We present 3 patients (2 travelers and 1 immigrant) in whom a rash was the presenting manifestation of Zika virus infection. Prompt diagnosis optimizes outcomes in these patients, improves the management of severe disease, and minimizes the risk of local transmission by Aedes albopictus, now a potential local vector for the virus due to its presence in areas along Spain's Mediterranean coast.

Fungal Fermentation of Lignocellulosic Biomass for Itaconic and Fumaric Acid Production.

The production of high-value chemicals from natural resources as an alternative for petroleum-based products is currently expanding in parallel with biorefinery. The use of lignocellulosic biomass as raw material is promising to achieve economic and environmental sustainability. Filamentous fungi, particularly Aspergillus species, are already used industrially to produce organic acid as well as many enzymes. The production of lignocellulose-degrading enzymes opens the possibility for direct fungal fermentation towards organic acids such as itaconic acid (IA) and fumaric acid (FA). These acids have wide-range applications and potentially addressable markets as platform chemicals. However, current technologies for the production of these compounds are mostly based on submerged fermentation. This work showed the capacity of two Aspergillus species (A. terreus and A. oryzae) to yield both acids by solid-state fermentation and simultaneous saccharification and fermentation. FA was optimally produced at by A. oryzae in simultaneous saccharification and fermentation (0.54 mg/g wheat bran). The yield of 0.11 mg IA/g biomass by A. oryzae is the highest reported in the literature for simultaneous solid-state fermentation without sugar supplements.

Estudio preliminar de las características del intento de suicidio en la provincia de Granada / Preliminary study of the characteristics of attempted suicide in the province of Granada

Fundamento. Los suicidios en España representan un número de muertes mayor que otras muertes traumáticas. Los comportamientos suicidas no mortales se producen en una proporción mayor que los que tienen fin mortal. Las causas de esta conducta son múltiples y es importante conocerlas para poder prevenirlas. El objetivo del presente trabajo es describir las características del comportamiento suicida no mortal en la provincia de Granada. Método. Estudio descriptivo retrospectivo de las características del comportamiento suicida no mortal en Granada durante los años 2008 y 2009, según la base de datos del Servicio Provincial 061 de Granada. La muestra ha sido todas las demandas realizadas a este servicio en las que en el motivo literal de la alerta figuraron los términos suicidio, autolesióno amenaza suicida. El análisis estadístico se ha realizado con el programa SPSS 15.0. Se analizó la variable conducta suicidano mortal respecto de las variables independientes: sexo, edad, mes, día de la semana, franja horaria, distrito sanitario, resolución de la demanda (prioridad asignada) y reintentos. Resultados. Se analizaron en total 535 demandas tipificadas como lesión autoinflingida intencionalmente por medios no especificados. Se han encontrado diferencias estadísticamente significativas al comparar los datos de los dos años respecto del mes elegido, y en la relación entre rango deedad y franja horaria de los intentos de suicidio. Conclusiones. La caracterización de los intentos de suicidioen nuestra provincia ofrece información relevante, a pesar de sus limitaciones, y ayuda a determinar alguno de los parámetros en los que habrá que sustentar un futuro programa de intervención psicosocial para la prevención de estas conductas ajustado a los perfiles específicos de nuestra población (AU)

Background. Suicides account for a number of deaths that is higher than other traumatic deaths in Spain. Non-fatal suicidal behaviour occurs in a greater proportion than such behaviour with a deadly outcome. There are many causes for this behaviour and it is important to become familiar with them if it is to be prevented. The aim of this article is to describe the characteristics of non-mortal suicidal behaviour in the province of Granada. Method. A retrospective descriptive study of the characteristics of non-mortal suicidal behaviour in Granada during the years 2008 and 2009, according to the data base of the Provincial 061 Service in Granada. The sample includes the demands made to this service in which the literal reason for the alert included the terms: suicide, self-harm or the threat of suicide. The statistical analysis was done with the SPSS 15.0 program. We analyzed the variable non-mortal suicidal behaviour with respect to the independent variables: sex, age, month, day of the week, time slot, health district, resolution of the demand (assigned priority) and fur therattempts. Results. In total we analyzed 535 demands typified as intentional self-injury by un specified means. Statistically significant differences were found when comparing the data for the two years with respect to the month chosen, and in the relationship between age range and time slot of the suicide attempts. Conclusions. Despite its limitations, the characterization of suicidal behaviour in our province offers essential information, and could be useful in designing and developing aprogram of psychosocial intervention for the prevention of suicidal behaviour adjusted to the specific profiles of our population (AU)

Respiratory disease in aggregate quarry workers related to risk factors and Pi phenotype.

OBJECTIVE: To evaluate the respiratory health and its relationship with exposure to silica, smoking, alpha 1-antitrypsin, and Pi phenotype in aggregate quarries workers. METHODS: In a prevalence study, 378 subjects were studied, x-ray opacities and pulmonary function was analyzed in relation to cumulative dust exposure, smoking, alpha1- antitrypsin, and Pi phenotype. RESULTS: The adjusted odds ratio (OR) of round opacities (> or =0/1) was significantly related to smoking (P <0.001). The predicted forced expiratory volume in 1 second (FEV1) percentage had a negative relationship with the product dust. pack-years (P = 0.005). The OR of FEV1 <90% was 3.03 for smokers exposed to dust versus nonexposed nonsmokers (P = 0.049). The criteria for dust-tobacco interaction are satisfied. A subgroup with the highest level of alpha1-antitrypsin presented more opacities and worse pulmonary function. CONCLUSIONS: Radiologic alterations are found in relation to tobacco. The FEV1 has a negative relation with the product dust-tobacco. No alterations related to Pi phenotype are found. A subgroup with the highest alpha1-antitrypsin levels had more radiologic alterations and worse function.

Enfermedades pleuropulmonares asociadas con la inhalación de asbesto. Una patología emergente / Emerging pleuropulmonary diseases asociated with asbestos inhalation

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Differentiation-dependent redistribution of heparan sulfate in epithelial intestinal Caco-2 cells leads to basolateral entry of cytomegalovirus.

Human cytomegalovirus (HCMV) causes a broad spectrum of clinical manifestations in immunocompromised patients, including infection of the gastrointestinal tract. To investigate the role of epithelial cells in the gastrointestinal HCMV disease, we used the intestinal epithelial cell line Caco-2, which is permissive for HCMV replication. In differentiated Caco-2 cells, we showed previously that HCMV infection proceeds preferentially from the basolateral membrane, suggesting that receptors for HCMV may be contained predominantly in the basolateral membrane (A. Esclatine et al., 2000, J. Virol. 74, 513-517). Therefore, we examined expression and localization in Caco-2 cells of heparan sulfate (HS) proteoglycan and annexin II, previously implicated in initial events of HCMV infection. We observed that annexin II is expressed in Caco-2 cells, but is not essential for entry of HCMV. We showed that, during the differentiation process, HS, initially present on the entire surface of the membrane of undifferentiated cells, ultimately became sequestered at the basolateral cell surface of fully differentiated cells. We established by biochemical assays that membrane-associated HS proteoglycan mediates both viral attachment to, and subsequent infection of, Caco-2 cells, regardless of the cell differentiation state. Thus, the redistribution of HS is implicated in the basolateral entry of HCMV into differentiated Caco-2 cells.

[Malignant melanoma of the nasal cavity. Retrospective study. The analysis of p53 and p16INK4 expression]. / Melanoma maligno de fosas nasales. Estudio retrospectivo. Análisis de la expresión de p53 y p16INK4.

Five cases of malignant melanomata of the nasal cavities have been diagnosed and studied at ENT--and Anatomopathological Departments, between 1990 and 1997, the group ranging from 65 to 90 years, middle age 74.2. Paramount symptoms were epistaxis and lack of pain in all patients. Radical surgery was performed only in one case, followed by radiotherapy; the remainder were submitted to palliative treatment. We have reviewed the literature and also an immunohistochemical analysis about p53, p16INK4 and Rb oncogenes with the aim to establish its importance in these tumor's type. The whole group have showed high levels of p53 and MIB-1 and 60 percent a loss of oncogen p16 expression.

[The effects of dust inhalation in slate industry workers]. / Efectos del polvo inhalado en los trabajadores de la industria de pizarras.

BACKGROUND: Slate industries involve the risk of causing silicosis; these industries are now on the increase, which implies an increasing number of workers too. The effects of this type of mining on respiratory health are not yet known. SUBJECTS AND METHOD: A cross section study of active workers. Radiological and functional alterations, and their relation to risk factors, were assessed. RESULTS: A prevalence of 2.1% simple pneumoconiosis was found. The value of the FEV1 probed to be significantly related to smoking and to existence of nodulation of a 1/0 or higher profusion; these risk factors, when multiple regression is applied, work independently. CONCLUSION: Slate industry involves a risk of pneumoconiosis and other respiratory alterations.

Molecular characterisation of Hanseniaspora species.

The sequences of the internal transcribed spacers (ITS regions) and the 5.8S rRNA gene, together with the electrophoretic karyotypes of 27 strains representative of the six species belonging to the genus Hanseniaspora, were examined. From the analysis of the 5.8S rRNA gene and the ITS regions, the genus Hanseniaspora is monophyletic and can be divided into two subgroups. This subdivision was supported by electrophoretic chromosome patterns. Hanseniaspora guilliermondii, H. uvarum and H. valbyensis show 6-7 bands (8 to 9 chromosomes), while the second group comprises the species H. occidentalis, H. osmophila and H. vineae which have only 5 chromosomes.

Rotavirus infection induces cytoskeleton disorganization in human intestinal epithelial cells: implication of an increase in intracellular calcium concentration.

Rotavirus infection is the most common cause of severe infantile gastroenteritis worldwide. In vivo, rotavirus exhibits a marked tropism for the differentiated enterocytes of the intestinal epithelium. In vitro, differentiated and undifferentiated intestinal cells can be infected. We observed that rotavirus infection of the human intestinal epithelial Caco-2 cells induces cytoskeleton alterations as a function of cell differentiation. The vimentin network disorganization detected in undifferentiated Caco-2 cells was not found in fully differentiated cells. In contrast, differentiated Caco-2 cells presented Ca(2+)-dependent microtubule disassembly and Ca(2+)-independent cytokeratin 18 rearrangement, which both require viral replication. We propose that these structural alterations could represent the first manifestations of rotavirus-infected enterocyte injury leading to functional perturbations and then to diarrhea.

Tomografía computarizada de alta resolución en el diagnóstico de la neumoconiosis / High-resolution computerised tomography (HRCT) in the diagnosis of pneumoconiosis

El diagnóstico de neumoconiosis se realiza por medio de la radiografía de tórax en sujetos con historia de exposición a riesgo. La tomografía computarizada de alta resolución (TOAR), según los estudios publicados, es un método más sensible que la radiografía simple de tórax para valorar patología intersticial. En este trabajo se comparan los dos métodos (radiografía simple de tórax y TCAR) para el diagnóstico de la neumoconiosis en mineros del carbón, y se sugieren indicaciones del uso de la TCAR (AU)

Rotavirus infection induces an increase in intracellular calcium concentration in human intestinal epithelial cells: role in microvillar actin alteration.

Rotaviruses, which infect mature enterocytes of the small intestine, are recognized as the most important cause of viral gastroenteritis in young children. We have previously reported that rotavirus infection induces microvillar F-actin disassembly in human intestinal epithelial Caco-2 cells (N. Jourdan, J. P. Brunet, C. Sapin, A. Blais, J. Cotte-Laffitte, F. Forestier, A. M. Quero, G. Trugnan, and A. L. Servin, J. Virol. 72:7228-7236, 1998). In this study, to determine the mechanism responsible for rotavirus-induced F-actin alteration, we investigated the effect of infection on intracellular calcium concentration ([Ca(2+)](i)) in Caco-2 cells, since Ca(2+) is known to be a determinant factor for actin cytoskeleton regulation. As measured by quin2 fluorescence, viral replication induced a progressive increase in [Ca(2+)](i) from 7 h postinfection, which was shown to be necessary and sufficient for microvillar F-actin disassembly. During the first hours of infection, the increase in [Ca(2+)](i) was related only to an increase in Ca(2+) permeability of plasmalemma. At a late stage of infection, [Ca(2+)](i) elevation was due to both extracellular Ca(2+) influx and Ca(2+) release from the intracellular organelles, mainly the endoplasmic reticulum (ER). We noted that at this time the [Ca(2+)](i) increase was partially related to a phospholipase C (PLC)-dependent mechanism, which probably explains the Ca(2+) release from the ER. We also demonstrated for the first time that viral proteins or peptides, released into culture supernatants of rotavirus-infected Caco-2 cells, induced a transient increase in [Ca(2+)](i) of uninfected Caco-2 cells, by a PLC-dependent efflux of Ca(2+) from the ER and by extracellular Ca(2+) influx. These supernatants induced a Ca(2+)-dependent microvillar F-actin alteration in uninfected Caco-2 cells, thus participating in rotavirus pathogenesis.

Human cytomegalovirus infects Caco-2 intestinal epithelial cells basolaterally regardless of the differentiation state.

Human cytomegalovirus (CMV) causes severe disease in immunosuppressed patients and notably infects the gastrointestinal tract. To understand the interaction of CMV with intestinal epithelial cells, which are highly susceptible to CMV infection in vivo, we used the intestinal epithelial cell line Caco-2 and demonstrated that CMV enters predominantly through the basolateral surface of polarized Caco-2 cells. As shown by expression of all three classes of CMV proteins and by visualization of nucleocapsids by transmission electron microscopy, both poorly and fully differentiated Caco-2 cells were permissive to CMV replication. However, infection failed to produce infectious particles in Caco-2 cells, irrespective of the state of differentiation.

Inhibitory activity of constitutive nitric oxide on the expression of alpha/beta interferon genes in murine peritoneal macrophages.

We investigated the role of the constitutive nitric oxide (NO) in the expression of interferon (IFN) genes in mouse peritoneal macrophages (PM). The treatment of PM with L-arginine-N(G)-amine (AA), a potent inhibitor of NO-producing enzymes, resulted in a marked accumulation of IFN-alpha4 mRNA and, to a minor extent, of IFN-beta mRNA. In contrast, the expression of IFN-gamma mRNA, as well as tumor necrosis factor alpha and interleukin-6 mRNA, was not affected. Furthermore, a remarkable increase in the expression of the IFN regulating factor 1 (IRF-1), but not of IRF-2, mRNA was detected in AA-treated PM. To investigate whether the AA-induced activation of the IFN system correlates with the production and antiviral activity of IFN, the extent of encephalomyocarditis virus (EMCV) replication was monitored in AA-treated PM with respect to control cultures. AA treatment strongly inhibited, in a dose-dependent manner, EMCV yields in PM. Likewise, similar results were obtained by the addition of the NO-scavenger carboxyphenyl-tetramethylimidazoline-oxyl-oxide. In addition, inhibition of NO synthesis by N(G)-mono-methyl-L-arginine in PM strongly decreased virus replication in coculture of PM and EMCV-infected L929 cells, whereas no antiviral effect was observed in L929 cells alone. Moreover, the AA-mediated antiviral activity was abrogated in the presence of antibody to IFN-alpha/beta, whereas antibody to IFN-gamma was completely ineffective. Taken together, these results indicate that low levels of NO, constitutively released by resting PM, negatively regulate the expression and activity of IFN-alpha/beta in PM. We suggest that NO acts as a homeostatic agent in the regulation of IFN pathway expression in macrophages.

Rotavirus infection reduces sucrase-isomaltase expression in human intestinal epithelial cells by perturbing protein targeting and organization of microvillar cytoskeleton.

Rotavirus infection is the most common cause of severe infantile gastroenteritis worldwide. These viruses infect mature enterocytes of the small intestine and cause structural and functional damage, including a reduction in disaccharidase activity. It was previously hypothesized that reduced disaccharidase activity resulted from the destruction of rotavirus-infected enterocytes at the villus tips. However, this pathophysiological model cannot explain situations in which low disaccharidase activity is observed when rotavirus-infected intestine exhibits few, if any, histopathologic changes. In a previous study, we demonstrated that the simian rotavirus strain RRV replicated in and was released from human enterocyte-like Caco-2 cells without cell destruction (N. Jourdan, M. Maurice, D. Delautier, A. M. Quero, A. L. Servin, and G. Trugnan, J. Virol. 71:8268-8278, 1997). In the present study, to reinvestigate disaccharidase expression during rotavirus infection, we studied sucrase-isomaltase (SI) in RRV-infected Caco-2 cells. We showed that SI activity and apical expression were specifically and selectively decreased by RRV infection without apparent cell destruction. Using pulse-chase experiments and cell surface biotinylation, we demonstrated that RRV infection did not affect SI biosynthesis, maturation, or stability but induced the blockade of SI transport to the brush border. Using confocal laser scanning microscopy, we showed that RRV infection induces important alterations of the cytoskeleton that correlate with decreased SI apical surface expression. These results lead us to propose an alternate model to explain the pathophysiology associated with rotavirus infection.