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1.
mBio ; : e0035524, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990002

RESUMEN

The Type VI secretion system (T6SS) is a multicomponent apparatus, present in many Gram-negative bacteria, which can inhibit bacterial prey in various ecological niches. Pseudomonas aeruginosa assembles one of its three T6SS (H1-T6SS) to respond to attacks from adjacent competing bacteria. Surprisingly, repeated assemblies of the H1-T6SS, termed dueling, were described in a monoculture in the absence of an attacker strain; however, the underlying mechanism was unknown. Here, we explored the role of H2-T6SS of P. aeruginosa in triggering H1-T6SS assembly. We show that H2-T6SS inactivation in P. aeruginosa causes a significant reduction in H1-T6SS dueling and that H2-T6SS activity directly triggers retaliation by the H1-T6SS. Intraspecific competition experiments revealed that elimination of H2-T6SS in non-immune prey cells conferred protection from H1-T6SS. Moreover, we show that the H1-T6SS response is triggered independently of the characterized lipase effectors of the H2-T6SS, as well as those of Acinetobacter baylyi and Vibrio cholerae. Our results suggest that H1-T6SS response to H2-T6SS in P. aeruginosa can impact intraspecific competition, particularly when the H1-T6SS effector-immunity pairs differ between strains, and could determine the outcome of multistrain colonization.IMPORTANCEThe opportunistic pathogen Pseudomonas aeruginosa harbors three different Type VI secretion systems (H1, H2, and H3-T6SS), which can translocate toxins that can inhibit bacterial competitors or inflict damage to eukaryotic host cells. Unlike the unregulated T6SS assembly in other Gram-negative bacteria, the H1-T6SS in P. aeruginosa is precisely assembled as a response to various cell damaging attacks from neighboring bacterial cells. Surprisingly, it was observed that neighboring P. aeruginosa cells repeatedly assemble their H1-T6SS toward each other. Mechanisms triggering this "dueling" behavior between sister cells were unknown. In this report, we used a combination of microscopy, genetic and intraspecific competition experiments to show that H2-T6SS initiates H1-T6SS dueling. Our study highlights the interplay between different T6SS clusters in P. aeruginosa, which may influence the outcomes of multistrain competition in various ecological settings such as biofilm formation and colonization of cystic fibrosis lungs.

2.
Public Health ; 190: 168-172, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33341278

RESUMEN

OBJECTIVES: Based on the legal framework regulating the advertisement of food supplements in the EU, the aim of this article is to analyse the relationship between the presence of endorsers, the different types of health-related claims (H-RCs) and product content information. STUDY DESIGN: We applied a quantitative approach based on the content analysis of all radio spots broadcast throughout 2017 on full-service radio stations in Spain. METHODS: A corpus of 10,556 radio spots was obtained of the three radio stations with the highest audience levels (165 without repetitions). We incorporated data on the accumulated broadcast frequencies to supplement the content analysis specific to each radio spot with its weight in relation to the overall advertising discourse. We developed a coding scheme to assess the type of endorser, the types of H-RCs, and the product content information. RESULTS: Results show that European directives are breached in different ways. Healthcare experts prevail in disease claims, although they are prohibited. Celebrities are the most widely used endorsers (25%) in the function and reduction of disease risk claims. In addition, although these types of claims require substantiation by authorised ingredient, 73% of H-RCs lack this information. CONCLUSIONS: The high presence of illicit H-RCs and endorsers, such as physicians, and the omission of compulsory product information suggest that public administrations must apply stricter monitoring and sanctioning mechanisms to dissuade advertisers from further breaches of the law and to protect consumers. Implications for public health policy are made.


Asunto(s)
Publicidad/legislación & jurisprudencia , Suplementos Dietéticos , Etiquetado de Alimentos/legislación & jurisprudencia , Alimentos/normas , Etiquetado de Productos/legislación & jurisprudencia , Publicidad/métodos , Humanos , Legislación Alimentaria , España
3.
Life Sci Space Res (Amst) ; 21: 49-64, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31101155

RESUMEN

The pumice volcanic samples could have possible connections to the evolution of life and give us insight about their bio-geochemical processes related. In this regard, the samples from the volcanic eruption from La Restinga (El Hierro, Spain) in 2011 have been mainly studied by means of Raman spectroscopy. The research also includes analysis of XRD, Scanning Electron Microscopy and Optical Microscopy to support the Raman analysis. The results show that the Raman methods and mineral analyses are in strong agreement with the results obtained from other authors and techniques. The internal white foamy core (WFC) of the studied pumice samples shows amorphous silica, Fe-oxides, Ti-oxides, quartz, certain sulfates, carbonates, zeolites and organics. On the other hand, the external part (dark crust - DC) of these samples mainly presents primary-sequence mineralogy combined with some secondary alteration minerals such as olivine, feldspar, pyroxene, amorphous silica, and Fe-oxide. Raman spectroscopy detected other minerals not yet reported on these samples like barite, celestine and lepidocrocite. Also, the different chemometric and calibration methods for Raman spectroscopy in elemental composition, mineral classification and structural characterization has been successfully applied. From the astrobiological perspective, the research was also complemented with comparisons to other similar samples from terrestrial analogs. The main consideration was taking into account the proposed hypothesis regarding the potential behavior of the pumice as a substrate for the evolution of life. Furthermore, the detailed analysis from La Restinga eruption is coherent with the mineral phases and processes discussed from previous literature. The white internal part fulfills the conditions to work as an organic reservoir, confirmed by the detection of organic matter and selected minerals that could be used as energy sources for bacterial communities. The external layers of the samples work as a shielding layer to protect the organics from decay in extreme conditions. Finally, here we have demonstrated that the characteristics and advantages of Raman spectroscopy could help to assess and understand the possible biogenicity and alteration processes of any geological sample to be found on Mars.


Asunto(s)
Exobiología , Sedimentos Geológicos/análisis , Minerales/análisis , Espectrometría Raman/métodos , Difracción de Rayos X
4.
J Hazard Mater ; 373: 425-436, 2019 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-30939425

RESUMEN

The secondary products of an arsenopyrite-bearing mine waste dump were characterized in order to ascertain their mineralogical, chemical and environmental features and to appraise their role in the abatement of As in the environment. To this purpose, representative surface samples of weathered sulfides (including cemented phases) and hardpan samples were collected and studied by X-ray powder diffraction (XRD), polarized light microscopy, electron microprobe analysis (EMPA), micro-Raman spectroscopy and digestion, extraction and leaching methods. Scorodite, amorphous ferric arsenates (AFA), elemental sulfur, hydronium jarosite, goethite, hematite and hydrous ferric oxides were the secondary products identified in the mine wastes. The hardpan was mainly constituted by gangue minerals, including sulfides (arsenopyrite and pyrite/marcasite) with different weathering degrees, cemented by cracked yellow phases corresponding to AFA with Fe/As molar ratios of 1.14-1.85 and elemental sulfur. These cracked compounds were also the binding agent in the other cemented phases. Hydronium jarosite and Fe (oxyhydr)oxides were enriched in As, showing values of 0.19-3.98 and 0.81-7.49 wt.% As2O5, respectively. The As leachability and lability from hardpan and cemented phases were not decreased as compared to those from the other weathered phases not showing cementation in the mine waste dump.

6.
Artículo en Inglés | MEDLINE | ID: mdl-27106813

RESUMEN

We test the capabilities of in situ Raman spectroscopy for non-destructive analysis of degradation processes in invaluable masterpieces, as well as for the characterization of minerals and prehistoric rock-art in caves. To this end, we have studied the mechanism of decay suffered by the 15th-century limestone sculptures that decorate the retro-choir of Burgos Cathedral (N Spain). In situ Raman probe detected hydrated sulfate and nitrate minerals on the sculptures, which are responsible for the decay of the original limestone. In addition, in situ Raman analyses were performed on unique speleothems in El Soplao Cave (Cantabria, N Spain) and in the Gruta de las Maravillas (Aracena, SW Spain). Unusual cave minerals were detected in El Soplao Cave, such as hydromagnesite (Mg5(CO3)4(OH)2·4H2O), as well as ferromanganese oxides in the black biogenic speleothems recently discovered in this cavern. In the Gruta de las Maravillas, gypsum (CaSO4·2H2O) was identified for the first time, as part of the oldest cave materials, so providing additional evidence of hypogenic mechanisms that occurred in this cave during earlier stages of its formation. Finally, we present preliminary analyses of several cave paintings in the renowned "Polychrome Hall" of Altamira Cave (Cantabria, N. Spain). Hematite (Fe2O3) is the most abundant mineral phase, which provides the characteristic ochre-reddish color to the Altamira bison and deer paintings. Thus, portable Raman spectroscopy is demonstrated to be an analytical technique compatible with preserving our cultural and natural heritage, since the analysis does not require physical contact between the Raman head and the analyzed items.

7.
Transplant Proc ; 47(8): 2324-7, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26518917

RESUMEN

BACKGROUND: Donors after brain death (DBD) older than 60 years have become 46.8% of our current activity, with higher risk of renal discard rate (RDR). Assessment of kidney suitability requires complementary strategies: macroscopic evaluation, kidney biopsy score (KBS), and renal hemodynamic evaluation with the Pulsatile Perfusion Machine (PPM). METHODS: Descriptive, cross-sectional, comparative study of kidneys procured and RDR, comparing 3 time periods: 2000 to June 2004, when only KBS were used; July 2004 to 2008 (introduction of PPM and learning period); and 2009 to 2013 (experienced use of PPM). Transplantation criteria were KBS <3 and PPM renal resistance <0.4 mm Hg/mL/min and arterial renal flow >70 mL/min. RESULTS: Between 2000 and 2013, a 59.2% reduction in DBD kidneys was observed. However, older kidneys had an increase from 33.5% to 46.8%. The RDR had increased, comparing the first to the third period from 25.4% to 38.3%. However, the RDR was lower when kidneys were evaluated with PPM than those evaluated only with KBS and preserved in cold storage (CS) (21.4% versus 43.7%). There was a significant difference in cold ischemia time, because CS kidney was grafted before PPM. During the third period, more kidneys with KBS ≥4 were assigned to PPM. CONCLUSIONS: Notwithstanding the decrease in DBD-procured kidneys and the increase in older kidneys during last period, the use of PPM allowed low DR compared with CS. A bias in the results of PPM could be generated when kidneys with higher KBS were excluded from PPM. The use of KBS only to decide acceptance could preclude the use of an additional tool to evaluate suitability.


Asunto(s)
Muerte Encefálica/fisiopatología , Trasplante de Riñón , Preservación de Órganos , Flujo Pulsátil/fisiología , Factores de Edad , Anciano , Estudios Transversales , Criopreservación , Humanos , Persona de Mediana Edad , Donantes de Tejidos , Obtención de Tejidos y Órganos
8.
Ultrasound Obstet Gynecol ; 42(2): 201-6, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23303527

RESUMEN

OBJECTIVE: To evaluate the 2-year neurodevelopmental outcome of full-term, small-for-gestational-age (SGA) newborns with normal placental function, according to current criteria based on umbilical artery Doppler findings. METHODS: A cohort of consecutive full-term, SGA newborns with normal prenatal umbilical artery Doppler was compared with a group of full-term, appropriate-for-gestational-age (AGA) infants sampled from our general neonatal population. Neurodevelopmental outcome was evaluated at 24 months' corrected age using the Bayley Scales of Infant and Toddler Development, 3(rd) Edition (Bayley-III), which evaluates cognitive, language, motor, social-emotional and adaptive competencies. The effect of the study group on each domain was adjusted with MANCOVA and logistic regression for gestational age at delivery, socioeconomic status, gender, tobacco smoking and breastfeeding. RESULTS: A total of 223 infants (112 SGA and 111 AGA) were included. The groups differed significantly with respect to socioeconomic status and gestational age at delivery. All studied neurodevelopmental domains were poorer in the SGA group, reaching significance for the cognitive (92.9 vs 100.2, adjusted P = 0.027), language (94.7 vs 101, adjusted P = 0.025), motor (94.2 vs 100, adjusted P = 0.027) and adaptive (89.2 vs 96.5, adjusted P = 0.012) scores. Likewise, the SGA group had a higher risk of low scores in language (odds ratio (OR) = 2.63; adjusted P = 0.045) and adaptive (OR = 2.72; adjusted P = 0.009) domains. CONCLUSIONS: Compared with normal-sized babies, full-term SGA infants, without placental insufficiency defined according to currently used criteria, have lower 2-year neurodevelopmental scores. These data challenge the concept that SGA fetuses with normal umbilical artery Doppler are 'constitutionally small' but otherwise completely normal.


Asunto(s)
Discapacidades del Desarrollo/etiología , Recién Nacido Pequeño para la Edad Gestacional/psicología , Análisis de Varianza , Estudios de Casos y Controles , Preescolar , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Discapacidades del Desarrollo/fisiopatología , Femenino , Retardo del Crecimiento Fetal/fisiopatología , Retardo del Crecimiento Fetal/psicología , Edad Gestacional , Humanos , Recién Nacido , Trastornos del Lenguaje/etiología , Trastornos del Lenguaje/fisiopatología , Edad Materna , Placenta/irrigación sanguínea , Placenta/fisiología , Embarazo , Efectos Tardíos de la Exposición Prenatal , Trastornos Psicomotores/etiología , Trastornos Psicomotores/fisiopatología , Factores Socioeconómicos , Ultrasonografía Doppler , Arterias Umbilicales/fisiología
9.
J Control Release ; 165(3): 163-72, 2013 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-23178664

RESUMEN

BACKGROUND AND AIMS: CD40-CD40L interactions appear to play an important role in the pathogenesis of experimental colitis. We tested the effect and investigated the underlying mechanism of action of systemically administered antisense oligonucleotide (ASO) targeting CD40 formulated in amphoteric liposomes (nov038/CD40). The charge characteristics of the amphoteric liposomes (anionic surface charge at physiological pH that becomes cationic at low pH), facilitate efficient sequestration of the ASO inside the liposomes at low pH and the direction of the carriers towards macrophages and dendritic cells under physiological conditions. METHODS: Colitis was induced in Balb/c mice using 2,4,6-Trinitrobenzene sulphonic acid (TNBS) and treated with nov038/CD40. Disease was monitored by body weight, histology, cytokine profiling and changes in immune cell populations. CD40 expression on different cell subsets was analyzed by flow cytometry. An antigen challenge model was used to determine neoimmunity under CD40 modulation. RESULTS: Administration of nov038/CD40 inhibited the development of TNBS colitis as assessed by weight loss, histology and cytokine profiles; unformulated CD40 ASO or nov038 encapsulating an unrelated ASO (nov038/SCR) were ineffective. The novel agent is potent as it completely suppressed even established colitis with a single treatment and significantly reduced T-cell activation as well as levels of pro-inflammatory mediators in serum. The inhibition of CD40 specifically occurred in macrophages, but not in B-cells. In contrast to prednisolone, standard treatment for inflammatory bowel diseases (IBD) that is effective in a single administration and involves extensive immunosuppression, nov038/CD40 did not affect the number of B- or Treg cells. Eventually, we observed a largely intact neoimmunity under conditions of a CD40 inhibition. CONCLUSIONS: Administration of nov038/CD40, but neither naked CD40 ASO nor nov038/SCR, prevents the development and treats established colitis in mice. Delivery of CD40 ASO in nov038 is highly cell-specific as it selectively suppresses CD40 on macrophages, but not on B-cells; the novel agent has strong anti-inflammatory characteristics without being immunosuppressive.


Asunto(s)
Antígenos CD40 , Colitis/tratamiento farmacológico , Oligonucleótidos Antisentido/administración & dosificación , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Quimiocina CXCL10/sangre , Colitis/inducido químicamente , Colitis/inmunología , Colitis/patología , Femenino , Interleucina-6/sangre , Liposomas , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Oligonucleótidos Antisentido/farmacocinética , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Ácido Trinitrobencenosulfónico
10.
Pediatr Obes ; 7(1): 39-43, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22434738

RESUMEN

BACKGROUND: Prenatal weight partitioning is gender specific, and infants born small for gestational age (SGA) have a lower fat mass and a lower fat-free mass than infants born appropriate for gestational age (AGA). Follistatin is an adipokine with adipogenic properties. OBJECTIVES: We examined whether follistatin circulates in the human foetus at term birth and, if so, whether cord blood follistatin relates to birthweight and neonatal body composition. METHODS: The study population was comprised of 248 term newborns (128 girls, 120 boys; 133 AGA, 115 SGA). The main outcome measures used for the study were birthweight, follistatin and insulin in umbilical cord serum, and neonatal body composition by absorptiometry. RESULTS: Follistatin was detectable in all cord serum samples. Cord follistatin concentrations were similar in girls and boys, being about 25% higher (P < 0.001) in SGA than AGA infants. In SGA infants, higher follistatin concentrations related to lower fat mass. CONCLUSION: [corrected] Follistatin is detectable in the circulation of the human foetus at term birth. The circulating levels of follistatin, an adipogenic adipokine, are higher in SGA than AGA infants, particularly so in SGA infants with a lower fat mass.


Asunto(s)
Peso al Nacer/fisiología , Composición Corporal/fisiología , Sangre Fetal/química , Folistatina/sangre , Edad Gestacional , Recién Nacido/sangre , Femenino , Sangre Fetal/metabolismo , Desarrollo Fetal , Humanos , Recién Nacido Pequeño para la Edad Gestacional/sangre , Insulina/análisis , Insulina/metabolismo , Masculino , Embarazo
11.
Ultrasound Obstet Gynecol ; 38(3): 288-94, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21557369

RESUMEN

OBJECTIVE: To evaluate the neurobehavioral outcomes of preterm infants with intrauterine growth restriction (IUGR), with and without prenatal advanced brain-sparing. METHODS: A cohort of IUGR infants (birth weight < 10(th) percentile with abnormal umbilical artery Doppler) born before 34 weeks of gestation was compared with a control group of appropriate-for-gestational age infants matched for gestational age at delivery. MCA pulsatility index was determined in all cases within 72 hours before delivery. Neonatal neurobehavior was evaluated at 40 weeks' ( ± 1) corrected age using the Neonatal Behavioral Assessment Scale. The effect of abnormal MCA pulsatility index (< 5(th) percentile) on each neurobehavioral area was adjusted for maternal smoking status and socioeconomic level, mode of delivery, gestational age at delivery, pre-eclampsia, newborn illness severity score and infant sex by multiple linear and logistic regression. RESULTS: A total of 126 preterm newborns (64 controls and 62 IUGR) were included. Among IUGR fetuses, the proportion of abnormal MCA Doppler parameters was 53%. Compared with appropriate-for-gestational age infants, newborns in the IUGR subgroup with abnormal MCA Doppler had significantly lower neurobehavioral scores in the areas of habituation, motor system, social-interactive and attention. Similarly, the proportion of infants with abnormal neurobehavioral scores was significantly higher in the IUGR subgroup with abnormal MCA Doppler parameters in the areas of habituation, social-interactive, motor system and attention. CONCLUSION: Abnormal MCA Doppler findings are predictive of neurobehavioral impairment among preterm newborns with IUGR, which suggests that this reflects an advanced stage of brain injury with a higher risk of abnormal neurological maturation.


Asunto(s)
Encéfalo/fisiopatología , Arterias Cerebrales/fisiopatología , Retardo del Crecimiento Fetal/fisiopatología , Ultrasonografía Doppler en Color , Ultrasonografía Prenatal , Arterias Umbilicales/fisiopatología , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/embriología , Arterias Cerebrales/diagnóstico por imagen , Desarrollo Infantil , Femenino , Retardo del Crecimiento Fetal/diagnóstico por imagen , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Embarazo , Resultado del Embarazo , Arterias Umbilicales/diagnóstico por imagen
12.
Am J Transplant ; 11(5): 1035-40, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21521471

RESUMEN

In this study we analyzed Spanish Post-Heart-Transplant Tumour Registry data for adult heart transplantation (HT) patients since 1984. Median post-HT follow-up of 4357 patients was 6.7 years. Lung cancer (mainly squamous cell or adenocarcinoma) was diagnosed in 102 (14.0% of patients developing cancers) a mean 6.4 years post-HT. Incidence increased with age at HT from 149 per 100 000 person-years among under-45s to 542 among over-64s; was 4.6 times greater among men than women; and was four times greater among pre-HT smokers (2169 patients) than nonsmokers (2188). The incidence rates in age-at-diagnosis groups with more than one case were significantly greater than GLOBOCAN 2002 estimates for the general Spanish population, and comparison with published data on smoking and lung cancer in the general population suggests that this increase was not due to a greater prevalence of smokers or former smokers among HT patients. Curative surgery, performed in 21 of the 28 operable cases, increased Kaplan-Meier 2-year survival to 70% versus 16% among inoperable patients.


Asunto(s)
Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/efectos adversos , Neoplasias Pulmonares/etiología , Adolescente , Adulto , Anciano , Femenino , Humanos , Incidencia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Sistema de Registros , Factores Sexuales , España
13.
Transplant Proc ; 42(8): 3011-3, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20970595

RESUMEN

INTRODUCTION: Malignancy is a major complication in the management of solid organ transplant patients. Skin cancers show a better prognosis than other neoplasms, but not all others are equal: Ideally, patient management must take into account the natural history of each type of cancer in relation to the transplanted organs. We sought to determine the prognosis of various groups of noncutaneous nonlymphomatous (NCNL) cancers after heart transplantation (HT). METHODS: We retrospectively analyzed the records of the Spanish Post-Heart-Transplant Tumour Registry, which collects data on posttransplant tumors in all patients who have undergone HT in Spain since 1984. Data were included in the study up to December 2008. We considered only the first NCNL post-HT tumors. RESULTS: Of 4359 patients, 375 developed an NCNL cancer. The most frequent were cancers of the lung (n=97; 25.9%); gastrointestinal tract (n=52; 13.9%); prostate gland (n=47; 12.5%; 14.0% of men), bladder (n=32; 8.5%), liver (n=14; 3.7%), and pharynx (n=14; 3.7%), as well as Kaposi's sarcoma (n=11; 2.9%). The corresponding Kaplan-Meier survival curves differed significantly (P<.0001; log-rank test), with respective survival rates of 47%, 72%, 91%, 73%, 36%, 64%, and 73% at 1 year versus 26%, 62%, 89%, 56%, 21%, 64%, and 73% at 2 years; and 15%, 51%, 77%, 42%, 21%, 64%, and 52% at 5 years post-diagnosis, respectively. CONCLUSION: Mortality among HT patients with post-HT NCNL solid organ cancers was highest for cancers of the liver or lung (79%-85% at 5 years), and lowest for prostate cancer (23%).


Asunto(s)
Trasplante de Corazón , Neoplasias/fisiopatología , Sistema de Registros , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Pronóstico , Estudios Retrospectivos , España , Tasa de Supervivencia
14.
Curr Pharm Des ; 16(9): 1063-80, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20030612

RESUMEN

Toll-like receptors (TLRs) are a family of key proteins that permit mammals to detect microbes and endogenous molecules, which are present in body fluids, cell membranes and cytoplasm. They confer mechanisms to the host for maintaining homeostasis, activating innate immunity and inducing signals that lead to the activation of adaptive immunity. TLR signalling induces the expression of pro-inflammatory and anti-viral genes through different and intricate pathways. However, persistent signalling can be dangerous and all members of the TLR family are involved in the pathogenesis of acute and chronic inflammation, autoimmunity, allergy, cancer and aging. The pharmaceutical industry has begun intensive work developing novel immunotherapeutic approaches based on both activation and inhibition of TLR triggering. Further, clinical trials are pending to evaluate TLR agonists as novel vaccine adjuvants and for the treatment of infectious diseases, allergic diseases and asthma. Since systemic, metabolic and neuroendocrine changes are elicited by inflammation, TLR activity is susceptible of regulation by hormones and neuroendocrine factors. Neuroendocrine mediators are important players in modulating different phases of TLR regulation contributing to the endogenous control of homeostasis through local, regional and systemic routes. Vasoactive intestinal peptide (VIP) is an important signal molecule of the neuroendocrine-immune network that has recently emerged as a potential candidate for the treatment of inflammatory and autoimmune disorders by controlling innate and adaptive immunity. This review shows current advances in the understanding of TLR modulation by VIP that could contribute to the use of this natural peptide as a therapeutic tool.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Inflamación/tratamiento farmacológico , Péptidos/administración & dosificación , Transducción de Señal/efectos de los fármacos , Receptores Toll-Like/agonistas , Receptores Toll-Like/antagonistas & inhibidores , Péptido Intestinal Vasoactivo/uso terapéutico , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Humanos , Mediadores de Inflamación/metabolismo , Modelos Biológicos , Péptidos/farmacología , Receptores Toll-Like/metabolismo , Receptores Toll-Like/fisiología , Péptido Intestinal Vasoactivo/farmacología
15.
Environ Technol ; 29(11): 1219-28, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18975854

RESUMEN

Two different methods, based on micellar electrokinetic capillary chromatography (MECC-DA) and high performance liquid chromatography (HPLC)-fluorescence detection, were studied to separate and determine 12 polynuclear aromatic hydrocarbons (PAHs) of 16 PAHs recommended by the Environmental Protection Agency (EPA) in sewage sludge. beta-cyclodextrin was used as a micelle precursor in a sodium borate buffer solution which included the surfactant sodium dodecyl sulphate (SDS) and the acetonitrile dissolvent. The following parameters: temperature, voltage, pH, concentrations of buffer solution and injection time, were optimized by an experimental design (Nemrodw programme). Furthermore, HPLC-fluorescence detection and separation conditions are reported. The mobile phase was acetonitrile-water in different percentages. Precision, accuracy, linearity and detection and quantification limits were determined. This method was applied in the analysis of sewage sludge from a wastewater depuration station in Crispijana (Alava, Spain). In this case, it is necessary to carry out a solid phase extraction step for its determination. The method was validated by the analysis of a certificated sample of LGC 6182, and finally samples of sewage sludge were analysed weekly for two years, obtaining in all cases results under the legal limits for the use of sewage sludge in agriculture.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Cromatografía Capilar Electrocinética Micelar/métodos , Hidrocarburos Policíclicos Aromáticos/análisis , Aguas del Alcantarillado/análisis , Fluorescencia , Sensibilidad y Especificidad , Eliminación de Residuos Líquidos
16.
Neuroimmunomodulation ; 15(1): 46-53, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18667799

RESUMEN

The vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide (VIP/PACAP) system is considered as a paradigm for the use of a neuroendocrine-immune mediator in therapy. We review the role of VIP in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis as a murine model of Crohn's disease. VIP treatment led to the recovery of clinical factors, the amelioration of parameters related to the recruitment and traffic of cell populations, and the balance of inflammatory mediators derived from granulocytes, antigen-presenting cells and T lymphocytes including Th1, Th2 and Th17. Finally, the most recent data validate its therapeutic role through the modulation of TLR2 and 4 receptors.


Asunto(s)
Enfermedad de Crohn/tratamiento farmacológico , Sistemas Neurosecretores/efectos de los fármacos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/inmunología , Péptido Intestinal Vasoactivo/farmacología , Animales , Células Presentadoras de Antígenos/efectos de los fármacos , Células Presentadoras de Antígenos/inmunología , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/fisiopatología , Modelos Animales de Enfermedad , Granulocitos/efectos de los fármacos , Granulocitos/inmunología , Humanos , Ratones , Neuroinmunomodulación/efectos de los fármacos , Neuroinmunomodulación/inmunología , Sistemas Neurosecretores/inmunología , Sistemas Neurosecretores/fisiopatología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Péptido Intestinal Vasoactivo/uso terapéutico
17.
Langmuir ; 24(16): 8667-71, 2008 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-18642858

RESUMEN

A comparative study of the chemical functionalization of undoped, n- and p-type GaN layers grown on sapphire substrates by metal-organic chemical vapor deposition was carried out. Both types of samples were chemically functionalized with 3-aminopropyltriethoxysilane (APTES) using a well-established silane-based approach for functionalizing hydroxylated surfaces. The untreated surfaces as well as those modified by hydroxylation and APTES deposition were analyzed using angle-resolved X-ray photoelectron spectroscopy. Strong differences were found between the APTES growth modes on n- and p-GaN surfaces that can be associated with the number of available hydroxyl groups on the GaN surface of each sample. Depending on the density of surface hydroxyl groups, different mechanisms of APTES attachment to the GaN surface take place in such a way that the APTES growth mode changes from a monolayer to a multilayer growth mode when the number of surface hydroxyl groups is decreased. Specifically, a monolayer growth mode with a surface coverage of approximately 78% was found on p-GaN, whereas the formation of a dense film, approximately 3 monolayers thick, was observed on n-GaN.


Asunto(s)
Electrones , Galio/química , Silanos/química , Rayos X , Hidroxilación , Modelos Moleculares , Conformación Molecular , Propilaminas , Análisis Espectral , Propiedades de Superficie
18.
HIV Med ; 9(4): 227-33, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18366446

RESUMEN

OBJECTIVES: To evaluate the impact of immigration on tuberculosis (TB)-HIV co-infection in Spain in a prospective cohort of HIV patients. METHODS: Among 7761 HIV patients, we evaluated 1284 with at least one episode of TB between 1987 and 2006. Variables were compared between immigrants and Spaniards. RESULTS: Incidence of TB decreased from 20 to five cases per 100 patient-years in 2006 (P<0.01) and was always higher in immigrants than in Spaniards. The proportion of immigrants increased, reaching almost 50% of both new cases of HIV and TB-HIV co-infection in 2006. In 34.4% of patients, TB and HIV infection were diagnosed within the same year; simultaneous diagnosis was more frequent in immigrants (83.3%vs. 16.7%, P<0.001). Mortality was associated independently with age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05], TB diagnosis before 1996 (HR 2.6, 95% CI 1.8-3.6), use of highly active antiretroviral treatment (HR 0.494, 95% CI 0.37-0.66) and CD4 cell count at TB diagnosis (HR 0.996, 95% CI 0.995-0.997). CONCLUSIONS: Immigrants have a major impact on the incidence of TB in HIV patients, slowing down the decreasing trend in Spain. Simultaneous diagnosis of the co-infection in immigrants reveals a need to intensify HIV case finding in immigrants in Spain.


Asunto(s)
Infecciones por VIH/epidemiología , Tuberculosis/epidemiología , Adulto , África/etnología , Américas/etnología , Asia/etnología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos , Emigrantes e Inmigrantes , Europa (Continente)/etnología , Femenino , Infecciones por VIH/inmunología , Humanos , Incidencia , Masculino , Morbilidad/tendencias , Estudios Prospectivos , Factores de Riesgo , España/epidemiología , Población Blanca
19.
J Hazard Mater ; 155(1-2): 51-7, 2008 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-18164545

RESUMEN

The complexity of the mechanisms underlying organic matter mineralization and nutrient removal in algal-bacterial photobioreactors during the treatment of residual wastewaters has severely hindered the development of mechanistic models able to accurately describe these processes. Artificial neural networks (ANNs) are capable of inferring the complex relationships existing between input and output process variables without a detailed description of the mechanisms governing the process, and should therefore be more suitable for the modeling of photosynthetically oxygenated systems. Thus, a neural network consisting of a single hidden layer with four neurons accurately predicted the steady-state operation of a continuous stirred tank photobioreactor during salicylate biodegradation by an algal-bacterial consortium. Despite its simplicity and the low number of data sets for ANN training (23), this network topology exhibited a satisfactory fit for both training and testing data with correlation coefficients of 99%. Although the use of ANNs for modeling conventional wastewater treatment systems is not novel, this work constitutes, to the best of our knowledge, the first reported application of ANNs to photosynthetically oxygenated systems and one of the few models for microalgae-based treatment processes. This modeling approach is therefore expected to contribute to improve the understanding of the complex relationships between light, temperature, hydraulic retention time, pollutant concentration and process removal efficiency, which would eventually promote the development of algal-bacterial processes as a cost effective alternative for the treatment of industrial wastewaters.


Asunto(s)
Reactores Biológicos , Chlorophyta/metabolismo , Redes Neurales de la Computación , Ralstonia/metabolismo , Salicilatos/metabolismo , Contaminantes Químicos del Agua/metabolismo , Biodegradación Ambiental , Modelos Biológicos , Oxígeno/metabolismo , Fotosíntesis , Eliminación de Residuos Líquidos/métodos , Purificación del Agua/métodos
20.
An Med Interna ; 24(8): 375-8, 2007 Aug.
Artículo en Español | MEDLINE | ID: mdl-18020876

RESUMEN

BACKGROUND: Antibiotics account for a high percentage of hospital pharmacy expenses. An elevated proportion of the prescriptions are considered inappropriate. Infectious diseases specialist could help other physicians in improving antibiotics prescriptions. METHODS: Treatments in all patients hospitalized in four surgical wards were checked daily and recommendations were made in cases with signs of inadequate antibiotics prescriptions. The program was carried out during for 4 months and the results were compared with a similar period of the previous year. RESULTS: 562 treatments of 393 patients were reviewed . Five hundred twenty four recommendations were made (90% of them were accepted). There was a significant reduction in the number of inadequate prescriptions. Antibiotic expenditure decreased by 29,262 euros (7,240 euros/month), implying a reduction of 2.35 euros/hospitalization-bed/day. There were no statistically significant differences in the amount of hospital resistant bacteria nor in mortality between the two periods. CONCLUSIONS: Following application of a non-compulsory control program, antibiotic prescription improved and expenditure decreased, with no change in mortality. Acceptation of the program by the physicians of the departments implicated was favourable.


Asunto(s)
Antibacterianos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Prescripciones de Medicamentos , Profesionales para Control de Infecciones , Antibacterianos/economía , Infección Hospitalaria/economía , Costos de los Medicamentos , Costos de Hospital , Humanos , Pacientes Internos , España
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