RHBDD2 overexpression promotes a chemoresistant and invasive phenotype to rectal cancer tumors via modulating UPR and focal adhesion genes.

The current standard of care for locally advanced rectal cancer (RC) is neoadjuvant radio-chemotherapy (NRC) with 5-fluorouracil (5Fu) as the main drug, followed by surgery and adjuvant chemotherapy. While a group of patients will achieve a pathological complete response, a significant percentage will not respond to the treatment. The Unfolding Protein Response (UPR) pathway is generally activated in tumors and results in resistance to radio-chemotherapy. We previously showed that RHBDD2 gene is overexpressed in the advanced stages of colorectal cancer (CRC) and that it could modulate the UPR pathway. Moreover, RHBDD2 expression is induced by 5Fu. In this study, we demonstrate that the overexpression of RHBDD2 in CACO2 cell line confers resistance to 5Fu, favors cell migration, adhesion and proliferation and has a profound impact on the expression of both, the UPR genes BiP, PERK and CHOP, and on the cell adhesion genes FAK and PXN. We also determined that RHBDD2 binds to BiP protein, the master UPR regulator. Finally, we confirmed that a high expression of RHBDD2 in RC tumors after NRC treatment is associated with the development of local or distant metastases. The collected evidence positions RHBDD2 as a promising prognostic biomarker to predict the response to neoadjuvant therapy in patients with RC.

[What do primary care physicians think about deprescription?] / ¿Qué opinan los médicos de atención primaria sobre la deprescripción?

INTRODUCTION: To learn about the perceptions and attitudes of family doctors regarding deprescription. MATERIAL AND METHODS: This is a cross-sectional study conducted at the Organización Sanitaria Integrada Bidasoa, Osakidetza. In November 2018, sessions were held at health centres on deprescribing for family doctors, following which the PACPD-12 questionnaire was handed out, translated into Spanish and adapted. The responses to the questionnaire were collected, together with the socio-demographic variables. RESULTS: Forty-two of the 58 doctors who received the survey responded (72%). One hundred percent considered deprescription beneficial in the current scenario. The drug groups that they most frequently considered deprescribing were the benzodiazepines, bisphosphonates and proton pump inhibitors. The main reasons they gave for deprescribing were to reduce harm from adverse effects and that the medication was of minimal benefit in the patient's circumstances, and they indicated that specific training in deprescribing and pharmacist alerts in the clinical history would facilitate deprescription. Barriers highlighted were lack of time, prescribing by other professionals, or resistance on the part of the patient or their family. CONCLUSIONS: Knowing what doctors think about deprescribing and its barriers and facilitators are necessary to plan a strategy to facilitate the practice. Although all the respondents indicated that they consider deprescription beneficial, they found barriers in their daily practice to their being able to implement it.

Impacto de la pandemia SARS-CoV-2 en el inicio de las prescripciones / Impact of the SARS-CoV-2 pandemic on the start of prescriptions

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Toxicology tailored low density oligonucleotide microarray for the thicklip grey mullets (Chelon labrosus): Biomarker gene transcription profile after caging in a polluted harbour.

In aquatic organisms inhabiting polluted waters genes are activated to build an adaptive/compensatory defence against the possible effects of pollutants. Such responses can be used as biomarkers of exposure to chemical compounds, outlining the molecular mechanisms activated under specific pollution scenarios. With the aim of exploiting such approach in environmental health assessment, toxicologically relevant gene fragments were sequenced in the thicklip grey mullet (Chelon labrosus) and a toxicologically tailored low-density (160 genes) oligonucleotide microarray was customised. The tool was validated comparing organ/sex specific gene expression profiles and characterising responses under laboratory exposure to model chemicals. Finally, juvenile mullets were caged in a polluted harbour and hepatic gene expression profiles analysed after 5 and 21 days of deployment. Cages were deployed in the inner (IH) and outer (OH) Pasaia harbour, Bay of Biscay. Mussels (Mytilus galloprovincialis) were also caged as biological matrix for chemical bioaccumulation analysis and stress biomarkers measurements. Slightly higher concentrations of chemicals (metals, tributyltin, PAHs, phthalates) were quantified in IH than in OH, fish bile metabolites also revealing higher availability of PAHs in IH. Lysosome membrane stability in mussels was reduced, indicating stress condition in both sites. The developed microarray discriminated mullets showing distinctive expression profiles depending on site and deployment time. Genes related to immune and hypoxia responses were regulated comparing IH and OH at day 5. Phase I and II biotransformation genes, such as cyp2, cyp3 and ugt, were up-regulated in IH, together with the aryl hydrocarbon receptor 2 (ahr2) and the ahr repressor. Similarly, TBT-binding proteins and genes involved in lipid metabolism (pparγ, cyp7) were up-regulated with deployment time. Even if nowadays higher throughput approaches for gene expression analyses are available, the developed mullet tool constitutes a comprehensive tool to assess molecular responses of mullets exposed to pollutants, although it remains to be explored whether it can be applied to assess pollutant exposure in active pollution monitorings and in environmental health assessment.

Mama ectópica en la región inguinal / Ectopic breast in the inguinal region

El tejido mamario tiene su origen hacia la cuarta semana del desarrollo fetal, aparecen engrosamientos ectodérmicos que se extienden a ambos lados desde las futuras axilas hasta la región inguinal, constituyendo las «líneas mamarias o lácteas». Durante la embriogénesis se produce una regresión espontánea de este tejido, a excepción del situado en la región torácica que da lugar a las mamas en el adulto. La regresión mamaria permite conservar solo una glándula a cada lado de la región pectoral. Cuando se produce un fallo en la regresión, se condiciona el desarrollo de estructuras mamarias ectópicas, las cuales tienen una presentación clínica variable. El caso de una mujer de 41 años, que presentó una tumoración inguinal derecha de un año de evolución, con crecimiento acelerado en los últimos meses. La biopsia confirmó que se trataba de una proliferación epitelial glandular benigna

The breast tissue originated in the fourth week of foetal development, comprising ectodermal thickening extending on both sides from the armpits to the inguinal region, i.e. the milk lines. During embryogenesis, spontaneous regression of this tissue occurs, except tissue located in the thoracic region, which gives rise to breast tissue in adults. Breast regression preserves only one gland on each side of the chest. Breast regression impairment leads to the development of ectopic breast tissue, the clinical presentation of which varies widely. We report the case of a 41-year-old woman who presented a right inguinal tumour of one year of development, with rapid growth in recent months. The biopsy confirmed that it was a benign glandular epithelial proliferation

Integrative assessment of the effects produced by Ag nanoparticles at different levels of biological complexity in Eisenia fetida maintained in two standard soils (OECD and LUFA 2.3).

There is a potential risk to increase the release of silver nanoparticles (Ag NPs) into the environment: For instance. in soils receiving sludge models estimate 0.007 mg Ag NPs kg-1 that will annually increase due to sludge or sludge incineration residues land-disposal. Thus, the concern about the hazards of nanosilver to soils and soil invertebrates is growing. Studies performed up to now have been focused in traditional endpoints, used limit range concentrations and employed different soil types that differ in physico-chemical characteristics. Presently, effects of Ag NPs have been measured at different levels of biological complexity in Eisenia fetida, exposed for 3 and 14 d to high but sublethal (50 mg Ag NPs kg-1) and close to modeled environmental concentrations (0.05 mg Ag NPs kg-1). Since characteristics of the exposure matrix may limit the response of the organisms to these concentrations, experiments were carried out in OECD and LUFA soils, the most used standard soils. High concentrations of Ag NPs increased catalase activity and DNA damage in OECD soils after 14 d while in LUFA 2.3 soils produced earlier effects (weight loss, decrease in cell viability and increase in catalase activity at day 3). At day 14, LUFA 2.3 (low clay and organic matter-OM-) could have provoked starvation of earthworms, masking Ag NPs toxicity. The concentration close to modeled environmental concentrations produced effects uniquely in LUFA 2.3 soil. Accurate physico-chemical characteristics of the standard soils are crucial to assess the toxicity exerted by Ag NPs in E. fetida since low clay and OM contents can be considered toxicity enhancers.

Digestive cell lysosomes as main targets for Ag accumulation and toxicity in marine mussels, Mytilus galloprovincialis, exposed to maltose-stabilised Ag nanoparticles of different sizes.

Bioavailability and toxicity of maltose-stabilised AgNPs of different sizes (20, 40 and 100 nm) in mussels were compared with bulk and aqueous forms of the metal through a two-tier experimental approach. In the first tier, mussels were exposed for 3 d to a range of concentrations (0.75, 75, 750 µg Ag/l) in the form of Ag20-Mal, Ag40-Mal, Ag100-Mal, bulk Ag and aqueous Ag (as AgNO3), as well as to the concentrations of maltose used in the formulation of NPs. Mortality, bioaccumulation, tissue and cell distribution and lysosomal responses were investigated. In the second tier, mussels were exposed for 21 d to Ag20-Mal, Ag100-Mal, bulk Ag and aqueous Ag at the lowest effective concentration selected after Tier 1 (0.75 µg Ag/l), biomarkers and toxicopathic effects were investigated. Aqueous Ag was lethal within 3 d at 75 µg Ag/l; Ag NPs or bulk Ag did not produce significant mortality at 750 µg Ag/l. Ag accumulation was limited and metallothionein gene transcription was not regulated although metal accumulation occurred in digestive, brown and stomach epithelial cells and in gut lumen after exposure to AgNPs and aqueous Ag starting at low concentrations after 1 d. Electrondense particles (<10 nm) in lysosomes and residual bodies after exposure to AgNPs contained Ag and S (X-ray). Intralysosomal metal accumulation and lysosomal membrane destabilisation were enhanced after exposure to all the forms of Ag and more marked after exposure to Ag20-Mal than to larger NPs. 21 d exposure to AgNPs provoked digestive cell loss and loss of digestive gland integrity, resulting in atrophy-necrosis in digestive alveoli and oedema/hyperplasia in gills (Ag NP), vacuolisation in digestive cells (aqueous Ag) and haemocyte infiltration of connective tissue (all treatments). Intralysosomal metal accumulation, lysosomal responses and toxicopathic effects are enhanced at decreasing sizes and appear to be caused by Ag+ ions released from NPs, although the metal was not substantially accumulated.

Effects of PVP/PEI coated and uncoated silver NPs and PVP/PEI coating agent on three species of marine microalgae.

In the last years, applications for silver nanoparticles (Ag NPs) continue to increase together with the concerns about their potential input and hazards in aquatic ecosystems, where microalgae are key organisms. The aim of the present study was to assess the relative sensitivity of three marine microalgae species with differences in cell wall composition/structure exposed to Poly N-vinyl-2-pirrolidone/Polyethyleneimine (PVP/PEI) coated 5nm Ag NPs and uncoated 47nm Ag NP. As limited attention has been paid to the role of coating agents in NP toxicity, the effect of PVP/PEI alone was also evaluated. After 72h in artificial seawater, 47nm Ag NPs formed around 1400nm size aggregates while PVP/PEI coated 5nm Ag NPs reached around 90nm. Ag+ release in seawater was around 3% for 47nm Ag NPs and 30% for PVP/PEI coated 5nm Ag NPs. PVP/PEI coated 5nm Ag NP aggregates entrapped the algal cells in a network of heteroaggregates, while uncoated 47nm Ag NPs interacted to a lesser extent with algae. The concentration of PVP/PEI coated 5nm Ag NPs that exerted the median effect (EC50) on algae growth pointed out differences in algae sensitivity: T. suecica was about 10 times more sensitive than I. galbana and P. tricornutum. Further, the coating agent alone was as toxic to algae as PVP/PEI coated 5nm Ag NPs, suggesting that presence of the coating agent was the main driver of toxicity of coated NPs. Uncoated 47nm Ag NPs instead, showed similar toxicity towards algae although P. tricornutum was slightly less sensitive than T. suecica and I. galbana, which agrees with the presence of a resistant silicified cell wall in the diatom. The present work demonstrates differences in sensitivity of three marine microalgae, possibly related to their cell surface and size characteristics.

Conciliación de la medicación en atención primaria tras el alta hospitalaria / Medication reconciliation in primary care after hospital discharge

Objetivos: El objetivo primario de este estudio es comprobar si la información de los cambios propuestos en el tratamiento habitual de los pacientes al alta hospitalaria se traslada a su hoja de tratamiento activo cuando acuden a atención primaria. Se plantean objetivos secundarios como analizar la media de medicamentos por paciente al ingreso y al alta; identificar otros factores que pudieran influir en la modificación del tratamiento durante el ingreso (edad del paciente o número de fármacos previamente indicados, entre otros). También se analiza la relación entre el centro de salud al que pertenece el paciente y la probabilidad de que se concilie su medicación cuando acude a atención primaria. Material y métodos: Se trata de un estudio transversal observacional, desarrollado en la Organización Sanitaria Integrada Bidasoa. Se incluyó a todos los pacientes mayores de 65 años polimedicados (que tomaban 5 o más fármacos) de la organización, dados de alta en el Hospital Bidasoa entre el 15 de octubre y el 11 de noviembre de 2012. Las altas producidas en este periodo se enviaron desde el hospital a cada responsable de seguridad del paciente de los centros de atención primaria, y a través de la revisión de la historia clínica de cada paciente se obtuvo información relativa a si habían acudido a su centro en los 15 días posteriores al alta, así como de si se efectuó alguna modificación en la hoja de tratamiento activo. Resultados: Doscientos sesenta y un pacientes (n = 261) fueron dados de alta en el periodo de estudio, de los cuales 80 cumplían los criterios de inclusión. El informe de alta de 39 de ellos (49%) proponía algún cambio en su hoja de tratamiento activo. De ellos, 35 (90%) se pusieron en contacto con atención primaria, y en 24 pacientes los cambios fueron incluidos en su hoja de tratamiento activo, lo que supone el 68% de los que contactaron con atención primaria y el 61% de los que hubieran requerido cambios. Conclusiones: Los resultados observados en este estudio nos llevan a pensar en la necesidad de establecer un programa de conciliación de la medicación para los pacientes polimedicados al alta hospitalaria. Además, consideramos interesante ahondar en los motivos por los cuales los pacientes que a pesar de haber acudido a atención primaria tras el alta hospitalaria, no vieron trasladados los cambios de la medicación a su hoja de tratamiento activo (AU)

Objectives: The primary objective of this study was to determine if changes prescribed in the usual treatment of patients at discharge from the hospital were updated in their active treatment sheet when they came to the Primary Care clinic. The secondary objectives included, determining whether the drug average varies between the admission and discharge, as well as, identifying other factors related to the modification of treatment during hospital admission including, among others, patient age or the number of drugs previously indicated. Finally, the relationship between the Primary Care Unit to which the patient belonged and the probability that the medication was reconciled was also examined. Material and methods: This is an observational cross-sectional study conducted in the Bidasoa Integrated Healthcare Organization. The study included every patient over 65 years old with multiple medication (taking 5 or more drugs) belonging to this organization, and discharged from Bidasoa Hospital between 15th October and 11th November 2012. The information on hospital discharges during this period was sent from the hospital to those responsible for patient safety in the Primary Health Care Centers. Each patient clinical history was reviewed in order to confirm if a visit (at least once in the first two weeks after discharge) had been made to their Primary Care Unit, and whether there had been a change in their active treatment sheet. Results: Two hundred sixty-one patients (n = 261) were discharged from Bidasoa Hospital in the study period, and 80 met the inclusion criteria. The discharge report proposed a change in the active treatment in 39 of them (49%). Of these, 35 (90%) attended a Primary Care clinic, and the changes were included in their active treatment sheet in 24 patients, representing 68% of those who contacted Primary Care, and 61% of those who would have required changes. Conclusions: The results demonstrate the need to establish a reconciliation medication program for patients on multiple medications after hospital discharge. Moreover, further studies are needed to investigate what may be the reasons why the changes to active treatment sheets are not taking place for some patients, despite these having visited Primary Care after having been discharged from hospital

[Medication reconciliation in primary care after hospital discharge]. / Conciliación de la medicación en atención primaria tras el alta hospitalaria.

OBJECTIVES: The primary objective of this study was to determine if changes prescribed in the usual treatment of patients at discharge from the hospital were updated in their active treatment sheet when they came to the Primary Care clinic. The secondary objectives included, determining whether the drug average varies between the admission and discharge, as well as, identifying other factors related to the modification of treatment during hospital admission including, among others, patient age or the number of drugs previously indicated. Finally, the relationship between the Primary Care Unit to which the patient belonged and the probability that the medication was reconciled was also examined. MATERIAL AND METHODS: This is an observational cross-sectional study conducted in the Bidasoa Integrated Healthcare Organization. The study included every patient over 65 years old with multiple medication (taking 5 or more drugs) belonging to this organization, and discharged from Bidasoa Hospital between 15th October and 11th November 2012. The information on hospital discharges during this period was sent from the hospital to those responsible for patient safety in the Primary Health Care Centers. Each patient clinical history was reviewed in order to confirm if a visit (at least once in the first two weeks after discharge) had been made to their Primary Care Unit, and whether there had been a change in their active treatment sheet. RESULTS: Two hundred sixty-one patients (n=261) were discharged from Bidasoa Hospital in the study period, and 80 met the inclusion criteria. The discharge report proposed a change in the active treatment in 39 of them (49%). Of these, 35 (90%) attended a Primary Care clinic, and the changes were included in their active treatment sheet in 24 patients, representing 68% of those who contacted Primary Care, and 61% of those who would have required changes. CONCLUSIONS: The results demonstrate the need to establish a reconciliation medication program for patients on multiple medications after hospital discharge. Moreover, further studies are needed to investigate what may be the reasons why the changes to active treatment sheets are not taking place for some patients, despite these having visited Primary Care after having been discharged from hospital.

Molecular cloning and measurement of telomerase reverse transcriptase (TERT) transcription patterns in tissues of European hake (Merluccius merluccius) and Atlantic cod (Gadus morhua) during aging.

Telomerase is a reverse transcriptase ribonucleoprotein that maintains the ends of linear chromosomes. This enzyme plays a major role in cell processes like proliferation, differentiation and tumorigenesis, being associated with aging and survival of species. In this study, the gene coding for TERT (Telomerase Reverse Transcriptase) of two commercial fish species, European hake (Merluccius merluccius) and Atlantic cod (Gadus morhua), has been partially cloned. A fragment of 1581bp (hake) and 633bp (cod) showed high homology (identity 74%, query cover 99%, E-value=0) with known Perciformes TERT sequences. TERT transcription patterns were assessed by qRT-PCR in different tissues of hake (brain, ovary, testis, muscle, skin, gills, liver and kidney) and cod (brain, muscle and skin) of different sizes/ages in order to understand its role in the physiological aging of teleosts. TERT was found to be ubiquitously transcribed in all tissues and size/age groups studied in both species. Significantly higher relative transcription levels (p<0.05) were found with increasing size/age of M. merluccius in the kidney, muscle, skin and gonad, the latter exhibiting particularly high relative transcription levels. Male hakes showed higher TERT relative transcription levels in the brain, gonad and liver than females, although these differences were not statistically significant (p<0.05). In G. morhua, higher TERT relative transcription levels were recorded in the muscle and brain of fry and juvenile individuals. Therefore, TERT relative transcription pattern exhibited a higher telomerase demand in early developmental stages and also in mature stages, suggesting tissue renewal or regeneration processes as a conserved mechanism for maintaining long-term cell proliferation capacity and preventing senescence. Thus, it can be concluded that TERT relative transcription level was species and tissue specific and changed with the age of fishes.

Carcinoma de Células Escamosas de Tiroides: A Propósito de un Caso / Primary squamous cell thyroid carcinoma

El carcinoma de células escamosas de tiroides (CCET) es un tumor infrecuente y agresivo. Su etiología es incierta. Ante la presencia de carcinoma escamoso en la glándula tiroides debe excluirse la posibilidad de infiltración de un tumor originado en una estructura adyacente o de metástasis de otros carcinomas. El tratamiento de elección es la cirugía radical. La mayoría de los pacientes fallecen antes del año debido a progresión local de la enfermedad. Presentamos el caso de un paciente con una masa tiroidea, con diagnóstico histológico de carcinoma escamoso (con inmunohistoquímca negativa para tiroglobulina, TTF1 y calcitonina y positiva para p63 y citok5). Los estudios clínicos, endoscópicos y radiológicos excluyeron otros sitios de origen de carcinoma escamoso. Fue tratado con quimio y radioterapia, falleciendo por progresión local luego de 9 meses.

Primary squamous cell thyroid carcinoma (PSCTC) is a rare and aggressive tumor of uncertain origin. When squamous carcinoma is diagnosed, it is mandatory to exclude the possibility of primary tumor arising from an adjacent structure or representing metastases from a primary growth elsewhere. Aggressive surgical resection is the treatment of choice. However, the prognosis is poor, with a median survival of less than a year. Death is usually secondary to progression of local disease. We report a case of a patient presenting with a thyroid mass; biopsy was consistent with squamous cell carcinoma. On immunohistochemistry tumor cells were negative for TTF1, thyroglobulin and calcitonin. Cancer cells were positive for p63 and citok5. Extensive workup excluded the possibility of extrathyroid origin. The patient was treated with chemoradiotherapy; he died 9 months later due to local progression.

Reutilization of thermostable polyester wastes by means of agglomeration with phenolic resins.

We report on the possibility of obtaining organic polymeric matrixes allowing the development of new high performance fire-resistant products by recycling downsized thermostable waste materials. Phenolic resins have been used as binders for recycled waste. Furthermore, considering that reinforced plastic triturations have superior properties (chemical, mechanical, water resistance, etc.) to wood agglomerates, significant advantages over conventional materials are anticipated. In summary, we propose a viable solution to some of the known problems caused by the consumption of wood and to the needs of strengthened plastic processing engineering. Using resins as a binder, several fire-resistant prototypes were prepared from polyester waste, and their mechanical properties, thermal stability, and fire-resistant properties were analyzed.

Effects of exposure to Prestige-like heavy fuel oil and to perfluorooctane sulfonate on conventional biomarkers and target gene transcription in the thicklip grey mullet Chelon labrosus.

Thicklip grey mullets Chelon labrosus inhabit coastal and estuarine areas where they can be chronically exposed to commonly released pollutants such as polycyclic aromatic hydrocarbons (PAHs) and perfluorinated compounds. These pollutants can also originate from accidental spills, such as the Prestige oil spill in 2002, which resulted in the release of a heavy fuel oil that affected coastal ecosystems in the Bay of Biscay. Peroxisome proliferation (PP), induced biotransformation metabolism, immunosuppression and endocrine disruption are some of the possible biological effects caused by such chemicals. With the aim of studying the effects of organic toxic chemicals on such biological processes at the transcriptional and at the cell/tissue level, juvenile mullets were exposed to the typical mammalian peroxisome proliferator perfluorooctane sulfonate (PFOS), and to fresh (F) and weathered (WF) Prestige-like heavy fuel oil for 2 and 16 days. First, fragments of genes relevant to biotransformation, immune/inflammatory and endocrine disruption processes were cloned using degenerate primers. Fuel oil elicited a significant PP response as proved by the transcriptional upregulation of palmitoyl-CoA oxidase (aox1), peroxisome proliferator activated receptor alpha (pparalpha) and retinoic X receptor, by the AOX1 activity induction and by the increased peroxisomal volume density. PFOS only elicited a significant induction of AOX1 activity at day 2 and of PPARalpha mRNA expression at day 16. All treatments significantly increased catalase mRNA expression at day 16 in liver and at day 2 in gill. Cyp1a transcription (liver and gill) and EROD activity were induced in fuel oil treated organisms. In the case of phase II metabolism only hepatic glutathione S-transferase mRNA was overexpressed in mullets exposed to WF for 16 days. Functionally, this response was reflected in a significant accumulation of bile PAH metabolites. WF treated fish accumulated mainly high molecular weight metabolites while F exposure resulted in accumulation of mainly low molecular ones. Fuel oil significantly regulated immune response related complement component C3 and hepcidin transcription followed by a significant regulation of inflammatory response related apolipoprotein-A1 and fatty acid binding protein mRNAs at day 16. These responses were accompanied by a significant hepatic inflammatory response with lymphocyte accumulations (IRLA) and accumulation of melanomacrophage centers (MMC). PFOS did not elicit any transcriptional response in the studied biotransformation and immune related genes, although histologically significant effects were recorded in IRLA and MMC. A significant reduction of lysosomal membrane stability was observed in all exposed animals. No endocrine disruption effects were observed in liver while brain aromatase mRNA was overexpressed after all treatments at day 2 and estrogen receptor alpha was downregulated under WF exposure at day 16. These results show new molecular and cellular biomarkers of exposure to organic chemicals and demonstrate that in mullets PP could be regulated through molecular mechanisms similar to those in rodents, although the typical mammalian peroxisome proliferator PFOS and heavy fuel oil follow divergent mechanisms of action.

Tissue- and cell-specific expression of metallothionein genes in cadmium- and copper-exposed mussels analyzed by in situ hybridization and RT-PCR.

Metallothioneins (MTs) are metal-inducible proteins that can be used as biomarkers of metal exposure. In mussels two families of MT isoforms (MT10 and MT20) have been characterized. In this study, mussels (Mytilus galloprovincialis) were exposed to 200 ppb Cd and 40 ppb Cu for 2 and 9 days to characterize the tissue and isoform specificity of metal-induced MT expression. Non-radioactive in situ hybridization demonstrated that both MT isoforms were mainly transcribed in digestive tubule epithelial cells, especially in basophilic cells. Weaker MT expression was detected in non-ciliated duct cells, stomach and gill epithelial cells, haemocytes, adipogranular cells, spermatic follicles and oocytes. RT-PCR resulted in cloning of a novel M. galloprovincialis isoform homologous to recently cloned Mytilus edulis intron-less MT10B isoform. In gills, Cd only affected MT10 gene expression after 2 days of exposure while increases in MT protein levels occurred at day 9. In the digestive gland, a marked increase of both isoforms, but especially of MT20, was accompanied by increased levels of MT proteins and basophilic cell volume density (Vv(BAS)) after 2 and 9 days and of intralysosomal metal accumulation in digestive cells after 9 days. Conversely, although metal was accumulated in digestive cells lysosomes and the Vv(BAS) increased in Cu-exposed mussels, Cu exposure did not produce an increase of MT gene expression or MT protein levels. These data suggest that MTs are expressed in a tissue-, cell- and isoform-specific way in response to different metals.

Prescripción de especialidades farmacéuticas genéricas (EFG) en atención primaria / Prescription of Generic Medicines in Primary Care

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Procesos linfoides B cutáneos con patrón nodular / Cutaneous B cell processes with nodular pattern

Cutaneous lymphomas are low grade malignant neoplasms with favourable prognosis. Those related to the germinal centre with nodular pattern may be: follicular lymphomas (LFC) or extranodal marginal zone B-cell lymphomas (LMC). They are difficult to tell apart, and from reactive processes like cutaneous follicular hyperplasia and cutis immunocytomas. The objective of this study was to check the incidence and the value of both histology and immunohistochemistry in differential diagnosis. Fifty six patients with cutaneous lymphomas were selected within the period 1995-2004. The biopsies were studied with hematoxilin eosin and immunohistochemistry. Thirty two out of the fifty six cutaneous lymphoid infiltrates were of T origin (57.1%) and twenty four of B origin (42.8%), ten out of this last figure (17.7%) were lymphoid processes with nodular pattern Four LFC, three LMC and three HLC were diagnosed. Convergent follicles with scarce mantle and germinal centres with monomorph celullarity were observed in the LFC. Among the LMC, follicles with prominent mantle and nests of monocitoid cells in the mantle, interfollicular zone and in the germinal centers observed. In the HLC macrophages with detritus were found in the germinal centers. LFC showed: CD20 (+), CD 10 (+), bcl-2 (+) or (-), and bcl-6 (+) in the follicle and in the interfollicular area. LMC showed: CD 20 (+), bcl-2 (-), CD 10 (+/-), and bcl-6 (+) in the follicle, and bcl-2 (+), CD10 (-/+) and bcl-6 (-) in the interfollicular area. The HLC results were: bcl-2 (-), bcl-6 (+) and CD 10 (-) in the follicle and bcl-2 (+), bcl-6 (-) and CD 10 (-) in the interfollicular zone. We conclude that lymphoid B cell processes with nodular pattern are unusual. Histology and immunohistochemistry proved to be useful in the differential diagnosis of these lymphomas, and for differentiating these from lymphoid hyperplasias or non tumoral hyperplasias.

Procesos linfoides B cutáneos con patrón nodular / Cutaneous B cell processes with nodular pattern

Cutaneous lymphomas are low grade malignant neoplasms with favourable prognosis. Those related to the germinal centre with nodular pattern may be: follicular lymphomas (LFC) or extranodal marginal zone B-cell lymphomas (LMC). They are difficult to tell apart, and from reactive processes like cutaneous follicular hyperplasia and cutis immunocytomas. The objective of this study was to check the incidence and the value of both histology and immunohistochemistry in differential diagnosis. Fifty six patients with cutaneous lymphomas were selected within the period 1995-2004. The biopsies were studied with hematoxilin eosin and immunohistochemistry. Thirty two out of the fifty six cutaneous lymphoid infiltrates were of T origin (57.1%) and twenty four of B origin (42.8%), ten out of this last figure (17.7%) were lymphoid processes with nodular pattern Four LFC, three LMC and three HLC were diagnosed. Convergent follicles with scarce mantle and germinal centres with monomorph celullarity were observed in the LFC. Among the LMC, follicles with prominent mantle and nests of monocitoid cells in the mantle, interfollicular zone and in the germinal centers observed. In the HLC macrophages with detritus were found in the germinal centers. LFC showed: CD20 (+), CD 10 (+), bcl-2 (+) or (-), and bcl-6 (+) in the follicle and in the interfollicular area. LMC showed: CD 20 (+), bcl-2 (-), CD 10 (+/-), and bcl-6 (+) in the follicle, and bcl-2 (+), CD10 (-/+) and bcl-6 (-) in the interfollicular area. The HLC results were: bcl-2 (-), bcl-6 (+) and CD 10 (-) in the follicle and bcl-2 (+), bcl-6 (-) and CD 10 (-) in the interfollicular zone. We conclude that lymphoid B cell processes with nodular pattern are unusual. Histology and immunohistochemistry proved to be useful in the differential diagnosis of these lymphomas, and for differentiating these from lymphoid hyperplasias or non tumoral hyperplasias.(AU)