C-Src, ERK1/2 and Rho kinasemediate hydrogen peroxide-induced vascular contraction in hypertension: Role ofTXA2, NAD(P)H oxidase andmitochondria

AIM: : The aim of this study was to analyse the signalling pathways involved in H2O2 vascular responses in hypertension. METHODS: Vascular function, thromboxane A2 (TXA2) production, oxidative stress and protein expression were determined in mesenteric resistance arteries (MRAs) from hypertensive (spontaneously hypertensive rats, SHR) and normotensive Wistar Kyoto (WKY) rats. RESULTS: H2O2 and the TP agonist U46619 induced greater contractile responses in MRA from SHR than WKY. Moreover, H2O2 increased TXA2 production more in SHR than in WKY. The c-Src inhibitor PP1 reduced H2O2 and U46619-induced contraction and TXA2 release in both strains. The ERK1/2 inhibitor PD98059 reduced H2O2 but not U46619-induced contraction only in SHR arteries. The Rho kinase inhibitor Y26372 reduced H2O2 and U46619-induced contractions only in SHR arteries. Basal c-Src, ERK1/2 and Rho kinase expression were greater in MRA from SHR than WKY. In SHR, the combination of PD98059 with the TP antagonist SQ29548 but not with Y27632 inhibited the H2O2 contraction more than each inhibitor alone. H2O2 and U46619 increased NAD(P)H oxidase activity and O2 production and decreased mitochondrial membrane potential in vessels from SHR. The effects induced by H2O2 were abolished by inhibitors of TXA2 synthase, ERK1/2 and c-Src. The mitochondrial antioxidant mitoTEMPO reduced H2O2-induced contraction and NAD(P)H oxidase activation. CONCLUSION: In arteries from WKY, c-Src mediates H2O2 contractile responses by modulating TXA2 release and TXA2 effect. In SHR, H2O2 induces c-Src dependent TXA2 release that provokes vascular contractile responses through Rho kinase, c-Src and O2 from NAD(P)H Oxidase and mitochondria. Moreover, ERK1/2 activation contributes to H2O2 contraction in SHR through effects on mitochondria/NAD(P)H Oxidase

The genus Tamarix (Tamaricaceae) in Crete (Greece)

A report on the genus Tamarix (Tamaricaceae) in Crete is provided. The previously recorded taxa are compared with new collections made on the island and with vouchers found at different herbaria. Three species were fully confirmed: T. nilotica and T. parviflora, collected in the field, and T. smyrnensis, found only in herbarium vouchers. The other previously reported taxa, T. dalmatica, T. hampeana, T. pallasii and T. tetrandra were not found; T. dalmatica was erroneously reported, the record of T. hampeana represents a fourth species but its identity requires further study, records of T. pallasii are probably misidentifications of T. nilotica and/or T. smyrnensis, and the record of T. tetrandra probably refers to T. parviflora. The presence of T. nilotica is documented, confirming that it has been historically overlooked and mistaken for T. smyrnensis. A morphological comparison between T. nilotica and T. smyrnensis is provided in order to avoid further confusion and misidentifications. A dichotomous key for the Tamarix species reported in Crete is provided.The FPU programme (Mº de Educación, Spain), the I+D+I project CGL2008-05056 (Mº de Educación y Ciencia, Spanish Government) and complementary supporting funds ACIE10-01, ACIE11-05 and ACIE13-08 (University of Alicante, Spain) made this research possible

Monitoring Coxiella burnetii Infection in Naturally Infected Dairy Sheep Flocks Throughout Four Lambing Seasons and Investigation of Viable Bacteria.

Progression of Coxiella burnetii infection in four naturally infected sheep flocks, and in their farm environment, was monitored throughout four lambing seasons. Flocks with an active infection were selected based on the presence of C. burnetii DNA in bulk-tank milk (BTM) and a high seroprevalence in yearlings during the previous milking period (Spring 2015). During four consecutive lambing seasons (2015/16-2018/19), samples were collected within 1 week after each lambing period from animals (vaginal swabs, milk and feces from ewes, and yearlings) and the environment (dust indoor sheep premises). BTM samples and aerosols (outdoors and indoors) were monthly collected between lambing and the end of milking. Real-time PCR analyses showed different trends in C. burnetii shedding in the flocks, with a general progressive decrease in bacterial shedding throughout the years, interrupted in three flocks by peaks of reinfection associated with specific management practices. A significant relationship was found between C. burnetii fecal shedding and the bacterial burden detected in dust, whereas shedding by vaginal route affected the detection of C. burnetii in indoor aerosols. Three genotypes were identified: SNP8 (three flocks, 52.9% of the samples), SNP1 (two flocks, 44.8% samples), and SNP5 (one flock, two environmental samples). Coxiella burnetii viability in dust measured by culture in Vero cells was demonstrated in two of the flocks, even during the fourth lambing season. The results showed that infection can remain active for over 5 years if effective control and biosafety measures are not correctly implemented.This work was funded by INIA—Spanish National Institute for Agricultural and Food Research and Technology (RTA2017-00055-C02-00), the European Regional Development Funds (ERDF), and the Basque Government. RÁ-A is beneficiary of a Ph.D. contract funded by INIA (FPI-2015-014). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.S

Role of the IFN I system against the VHSV infection in juvenile Senegalese sole (Solea senegalensis)

Senegalese sole is susceptible to marine VHSV isolates but is not affected by freshwater isolates, which may indicate differences regarding virus-host immune system interaction. IFN I induces an antiviral state in fish, stimulating the expression of genes encoding antiviral proteins (ISG). In this study, the stimulation of the Senegalese sole IFN I by VHSV infections has been evaluated by the relative quantification of the transcription of several ISG (Mx, Isg15 and Pkr) after inoculation with marine (pathogenic) and freshwater (non-pathogenic) VHSV isolates. Compared to marine VHSV, lower levels of RNA of the freshwater VHSV induced transcription of ISG to similar levels, with the Isg15 showing the highest fold induction. The protective role of the IFN I system was evaluated in poly I:C-inoculated animals subse‑ quently challenged with VHSV isolates. The cumulative mortality caused by the marine isolate in the control group was 68%, whereas in the poly I:C-stimulated group was 5%. The freshwater VHSV isolate did not cause any mortality. Furthermore, viral RNA fold change and viral titers were lower in animals from the poly I:C + VHSV groups than in the controls. The implication of the IFN I system in the protection observed was confirmed by the transcription of the ISG in animals from the poly I:C + VHSV groups. However, the marine VHSV isolate exerts a negative effect on the ISG transcription at 3 and 6 h post-inoculation (hpi), which is not observed for the freshwater isolate. This difference might be partly responsible for the virulence shown by the marine isolateThis study was funded by the project P09-CVI-4579 from Junta de Andalucía (proyectos de Excelencia de la Junta de Andalucía), and partially by the CSD2007-00002 Aquagenomics grant (funded by the program Consolider-Ingenio 2010) from the Ministerio de Educación y Ciencia (MEC). D. Alvarez-Torres was supported by a fellowship from Junta de Andalucía (Proyecto de Excelencia P09- CVI-4579)S

Somatic and germline analysis of a familial Rothmund-Thomson syndrome in two siblings with osteosarcoma

Rothmund–Thomson syndrome (RTS) is characterized by a rash that begins in the first few months of life and eventually develops into poikiloderma. Associated symptoms are alterations in the teeth, sparse hair, thin eyebrows, lack of eyelashes, low stature, bone abnormalities, hematological illnesses, gastrointestinal disease, malnutrition, cataracts, and predisposition to cancer, principally to bone tumors and skin cancer. Diagnostic certitude is provided by a genetic study involving detection of pathogenic variants of the RECQL4 gene. We hereby present a familiar case of RTS in two siblings from a Portuguese family, both diagnosed with osteosarcoma. Genomic analysis (203 genes) of both tumors as well as germline analysis of the RECQL4 gene, thus confirming the syndrome in the family, have been performed. The relevance of clinical recognition of the hallmarks of the disease and thus early diagnosis with early intervention is highlighted

Occupational health of immigrant workers in Spain (ITSAL Project): key informants survey

Objetivo: Caracterizar colectivos de inmigrantes trabajadores en España y conocer sus condiciones de salud laboral mediante informantes clave. Método: Estudio cualitativo exploratorio-descriptivo con entrevistas en profundidad realizado en 2006. Se identificaron organizaciones, asociaciones y colectivos relacionados con la población inmigrante en Alicante, Barcelona, Huelva, Madrid y Valencia, y se seleccionaron los más accesibles y representativos. Se entrevistó a 43 informantes clave procedentes de 34 asociaciones u organismos. Se realizó un análisis narrativo del contenido. Resultados: Se señalan dificultades para el reconocimiento de los daños a la salud derivados del trabajo por las situaciones de irregularidad y precariedad, por resistencia por parte de los contratadores o las entidades aseguradoras, y por desconocimiento de los inmigrantes. Los informantes coinciden en que los riesgos laborales en los inmigrantes no difieren de los riesgos de los trabajadores autóctonos en similares circunstancias, pero los inmigrantes padecerían exposiciones más frecuentes e intensas por el acceso mayoritario a puestos menos cualificados y por la necesidad de prolongar las jornadas de trabajo. También se destaca su desconocimiento general en relación con los derechos de protección y de salud en el trabajo, aunque algunos informantes detectan un crecimiento de su actividad reivindicativa a través de los sindicatos. Conclusiones: Este primer acercamiento ha permitido definir algunos condicionantes generales que influirán en la salud laboral de los inmigrantes. La información obtenida servirá de base para profundizar, mediante técnicas adicionales de carácter cualitativo y cuantitativo, en los problemas de salud laboral de los inmigrantes trabajadores en España dentro del marco del Proyecto Inmigración, Trabajo y Salud (ITSAL), actualmente en desarrollo.Objective: To describe the characteristics, working conditions, and occupational health situation of immigrant workers in Spain through key informants. Method: We performed a qualitative, exploratory and descriptive study using indepth interviews carried out in 2006. Organizations and associations working with immigrant collectives in Alicante, Barcelona, Huelva, Madrid and Valencia were identified and the most representative and accessible entities in each location were selected. Fortythree interviews were performed with key informants from 34 different organisms. A narrative content analysis was performed. Results: Informants described difficulties in having health problems recognized as workrelated, due to irregular and precarious employment, employers' and insurance companies' reluctance, and immigrants' lack of knowledge. Informants coincided in reporting that the occupational risks for immigrant workers did not differ from those affecting Spanish workers in the same occupations and circumstances. However, exposure to occupational risks was exacerbated in immigrants because of their greater presence in unqualified jobs and their economic need to prolong working hours. Immigrants had little knowledge of their occupational health and safetyrelated rights, although some informants detected an increase in empowerment in this area, mostly through greater participation in trade unions. Conclusions: This first step allowed us to identify some of the general factors influencing the health and safety of immigrant workers in Spain. This information will be used in a longterm, ongoing research project [Project Immigration, Work and Health (Proyecto Inmigración, Trabajo y Salud [ITSAL]), which aims to evaluate occupational health problems in inmigrants working in Spain through both qualitative and quantitative methods

Tamarix minoa (Tamaricaceae), a new species from the island of Crete (Greece) based on morphological and plastid molecular sequence data

Tamarix minoa is described from material collected on the S Aegean island of Crete (Kriti), Greece. A morphological comparison with the species considered to be closest, T. africana and T. hampeana, is provided. An original illustration showing the main morphological characters of the new species is also given, as are photographs of the new species in its habitat. The isolated phylogenetic position of T. minoa is shown to be strongly supported by plastid molecular sequence data (trnS-trnG, trnQ-rps16 and ndhF-rpl32), thus warranting its recognition at specific rank.National Geographic Society, research project “Human recreation versus plant diversity on maritime sands in Crete” (NGS grant no. 8573-08). The FPU programme (Mº de Educación, Spain), the I+D+I project CGL2008-05056 (Mº de Educación y Ciencia, Spanish Government), the project OAPN 354-2011 (Mº de Agricultura, Alimentación y Medio Ambiente, Spanish Government) and complementary supporting funds ACIE10-01, ACIE11-05 and ACIE13-08 (University of Alicante, Spain)

Toward a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolizing enzymes. Gene/drug pairs and barriers perceived in Spain

The development of clinica lpractice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance withr regard to adverse drug reactions.The poten-tial of pharmacogenomicbiomarkers has been extensively investigated in recent years.However,several barriers to implementing the use of pharmacogenomics testing exist.We conducted a survey among members of the Spanish Societies of Pharmacology and Clinical Pharmacology to obtain information about the perception of such barriers and to compare the perceptions of participants about the relative importance of majorgene/drug pairs.Of 11 potential barriers,the highest importance was attributed to lack of institutional support for pharmacogenomic stesting,and to the issues related to the lack of guidelines.Of the proposed gene/drug pairs the highest importance was assigned to HLA-B/abacavir, UGT1A1/irinotecan, and CYP2D6/tamoxifen.In this perspective article,we compare the relative importance of 29 gene/drugpairs in the Spanish study with that of the same pairs in the American Society for Clinical Pharmacology and Therapeutic sstudy,and we provide suggestions and areas of focus to develop a guide for clinical practice in pharmacogenomics testingThe work in the author’s laboratory is financed by Grants PS09/00943, PS09/00469, RETICS RIRAAF RD07/0064/0016, and CIBERehd from Instituto de Salud CarlosIII,Madrid, Spain, and by Grants GR10068 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Unio

Influence of two dietary fibers in the oral bioavailability and other pharmacokinetic parameters of ethinyloestradiol

P. 253-257Dietary fibers are widely used in hypoglycaemic, hypolipidemic, slimming diets. It is probable that their ingestion coincides with the oral administration of drugs and a modification of their pharmacokinetics can appear. In the present study, the influence of two soluble fibers (guar gum and psyllium) was evaluated on the pharmacokinetics of ethinyloestradiol (EE) when they were administered together to female rabbits via the oral route. Three groups of rabbits were used. All animals received 1 mg/kg of EE; this compound was administered alone in the control group and with 3.5 g of guar gum or psyllium in the other two groups. When guar gum was administered, there was a decrease in the extent of EE absorbed, but no change was observed in the rate of absorption. When psyllium was administered, the extent of EE absorbed increased slightly and the rate of absorption was slower.S