Análisis de la seroprevalencia frente a sarampión, rubeola y parotiditis en trabajadores sanitarios / Analysis of seroprevalence against measles, rubella and mumps in health workers of two health departments of the Valencian Community (Spain)

FUNDAMENTOS: El personal sanitario es un colectivo profesional expuesto a riesgos ocupacionales. El objetivo de este trabajo fue estimar la ausencia de seroprotección frente a sarampión, rubeola y parotiditis de los trabajadores sanitarios vinculados a dos Departamentos de Salud de la Comunidad Valenciana, considerando edad, sexo, categoría profesional, riesgo laboral y área de desempeño. MÉTODOS: Se realizó un estudio observacional transversal. Los datos fueron recogidos de informes de vigilancia de la salud, que incluían resultados serológicos de 2.674 trabajadores. Las variables sociodemográficas fueron: sexo; grupos de edad (18-34; 35-49; >50 años); clasificación del servicio (riesgo/no riesgo); categoría profesional; área de desempeño profesional (atención primaria/ atención hospitalaria). La variable dependiente fue la ausencia de inmunización frente a sarampión, rubeola y parotiditis identificada por ausencia de niveles serológicos. Para las enfermedades estudiadas se estimó la prevalencia de ausencia de seroprotección y se evaluó la asociación entre la no inmunización con el resto de variables. RESULTADOS: La prevalencia de no inmunización fue del 7,8%, 3,7% y 16,1% para sarampión, rubeola y parotiditis, respectivamente. El análisis mediante regresión logística mostró diferencias estadísticamente significativas en la prevalencia de no inmunización a sarampión en función de grupos de edad (ORa 11,8 y ORa 5,8) y área de desempeño (ORa 0,5), frente a parotiditis en función de grupos de edad (ORa 4,9 y ORa 3,6) y categoría profesional 1 (médicos, farmacéuticos, odontólogos y psicólogos) (ORa 0,6) y frente a rubeola en función del sexo (ORa 4,6). CONCLUSIONES: Es necesario potenciar la vacunación entre los sanitarios, especialmente en aquellos que ejercen sus funciones en áreas de riesgo y entre el personal de menor edad. La vacunación debe promoverse dentro de políticas de seguridad laboral.(AU)

BACKGROUND: Health Personnel are a professional group exposed to occupational risks. The aim of this paper was to estimate the absence of seroprotection against measles, rubella and mumps in health workers linked to two Health Departments of the Valencian Community (Spain) and to study the relationship with age, sex, professional category, occupational risk and performance área. METHODS: A cross-sectional observational study was made. Data were collected from health surveillance reports, which included serological results from 2,674 health workers. The socio-demographic variables were: sex, age groups (18-34; 35-49; >50 years), service classification (risk/no risk), professional category, professional performance area (primary care/hospital care) and the dependent variable was absence of immunization against measles, rubella and mumps identified by the absence of serological levels. For the diseases studied, the prevalence of absence of seroprotection was estimated and the association between non-immunization and the rest of variables was evaluated. RESULTS: Prevalence of non-immunization was 7.8%, 3.7% and 16.1% for measles, rubella and mumps, respectively. Logistic regression analysis showed a significant differences in the prevalence of non-immunization to measles according to age groups (adjusted OR 11.8 and adjusted OR 5.8) and professional performance area (adjusted OR 0.5), compared to mumps according to age groups (adjusted OR 4.9 and adjusted OR 3.6) and professional category 1 (doctors, pharmacists, dentists and psychologists) (adjusted OR 0.6) and against rubella according to sex (adjusted OR 4.6). CONCLUSIONS: It is necessary to maintain vaccination among health workers, especially those who perform their functions in risk areas and among younger personnel. Vaccination should be promoted within occupational safety policies.(AU)

Electrically Tunable Reactivity of Substrate-Supported Cobalt Oxide Nanocrystals.

First-row transition metal oxides are promising materials for catalyzing the oxygen evolution reaction. Surface sensitive techniques provide a unique perspective allowing the study of the structure, adsorption sites, and reactivity of catalysts at the atomic scale, which furnishes rationalization and improves the design of highly efficient catalytic materials. Here, a scanning probe microscopy study complemented by density functional theory on the structural and electronic properties of CoO nanoislands grown on Au(111) is reported. Two distinct phases are observed: The most extended displays a Moiré pattern (α-region), while the less abundant is 1Co:1Au coincidental (ß-region). As a result of the surface registry, in the ß-region the oxide adlayer is compressed by 9%, increasing the unoccupied local density of states and enhancing the selective water adsorption at low temperature through a cobalt inversion mechanism. Tip-induced voltage pulses irreversibly transform α- into ß-regions, thus opening avenues to modify the structure and reactivity of transition metal oxides by external stimuli like electric fields.

Structure-Activity Studies of Novel Di-substituted [1,2,5]oxadiazolo [3,4-b]pyrazine Analogs Targeting the A-loop Regulatory Site of p38 MAP Kinase.

INTRODUCTION: In the quest for novel allosteric inhibitors of the p38 MAP kinase, we recently described the A-loop regulatory site, identified by means of molecular modeling studies together with the disclosure of a small molecule hit with a moderate inhibitory profile. Starting from this structure, we subsequently identified two additional hits with simpler molecular structures from an in silico screening study, using a substructure search in the SciFinder database. After corroboration of their inhibitory profile, analysis of their structures permitted to conclude about the suitability of the [1,2,5]oxadiazolo[3,4-b]pyrazine (furazano[ 3,4-b]pyrazine) scaffold for the development of potent A-loop regulatory site p38 MAP kinase inhibitors. Accordingly, we report the synthesis and pharmacological evaluation of a series of di-substituted analogs with a potent inhibitory profile of p38 MAP kinase, as shown by in vitro assays of their capability to inhibit IL-1ß secretion in human monocyte-derived macrophages. OBJECTIVE: To find small molecule potent inhibitors of the p38 MAP kinase A-loop regulatory site. METHODS: Starting from this structure, we subsequently identified two additional hits with simpler molecular structures from an in silico screening study, using a substructure search in the SciFinder database. After corroboration of their inhibitory profile, we carried out a hit-tolead optimization process guided by molecular modeling using a [1,2,5]oxadiazolo[3,4- b]pyrazine (furazano[3,4-b]pyrazine) scaffold. RESULTS: We report the synthesis and pharmacological evaluation of a series of di-substituted analogs with a potent inhibitory profile of p38 MAP kinase, as shown by in vitro assays of their capability to inhibit IL-1ß secretion in human monocyte-derived macrophages. CONCLUSION: We describe in the present work a series of [1,2,5]oxadiazolo[3,4-b]pyrazine (furazano[3,4-b]pyrazine), which are potent inhibitors of IL-1ß secretion in human monocytederived macrophages allosteric modulators of the p38 MAP kinase A-loop regulatory site.

Discovery of novel 2,3,5-trisubstituted pyridine analogs as potent inhibitors of IL-1ß via modulation of the p38 MAPK signaling pathway.

Interleukin-1ß is a central mediator of innate immune responses and inflammation. It plays a key role in a wide variety of pathologies, ranging from autoinflammatory diseases to metabolic syndrome and malignant tumors. It is well established that its inhibition results in a rapid and sustained reduction in disease severity, underlining the importance of having a repertoire of drugs of this class. At present, there are only three interleukin-1ß blockers approved in the clinic. All of them are biologics, requiring parenteral administration and resulting in expensive treatments. In an exercise to identify small molecule allosteric inhibitors of MAP kinases, we discovered a series of compounds that block IL-1ß release produced as a consequence of a stimulus involved in triggering an inflammatory response. The present study reports the hit-to-lead optimization process that permitted the identification of the compound 13b (AIK3-305) an orally available, potent and selective inhibitor of IL-1ß. Furthermore, the study also reports the results of an in vivo efficacy study of 13b in a LPS endotoxic shock model in male BALB/c mice, where IL-1ß inhibition is monitored in different tissues.

Estado inmunológico frente a la Hepatitis B del personal sanitario en dos departamentos de salud de la Comunidad Valenciana (España) / Immunological Status against Hepatitis B among Healthcare Workers in Two Public Health Departments of the Valencian Community (Spain)

OBJETIVO: Estimar la prevalencia de inmunización frente al virus de la Hepatitis B del personal sanitario, vinculado a los Departamentos de Salud de Torrevieja y Elche-Crevillente, de la Comunidad Valenciana. MÉTODOS: Estudio descriptivo transversal en todos los trabajadores sanitarios de dos departamentos de Salud. Obtenida la muestra se identificó los niveles de anticuerpos de superficie del virus de la Hepatitis B a través de los resultados serológicos ubicados en las historias clínicas. Se consideró inmunizado a títulos de anti-HBs ≥ 10 mlU/ml. Las variables analizadas fueron categorizadas según: Departamento; Género; Edad (18-34; 35-49; > 50 años); categoría profesional (facultativos/Enfermería/Otro personal sanitario/Personal no sanitario); Servicio riesgo contagio (Si/No); Inmunidad (≥ 10 mlU/ml / < 10 mlU/ml / No Dato) y Vacunacion sistemática anti-HBs según fecha nacimiento (Si/No). RESULTADOS: El personal estudiado ascendió a 2674. Predominó el género femenino 68,8%, el grupo de edad 35-49 años, 52,8%, y la categoría profesional de Enfermería, 32,2%. Un 74,9% de los resultados serológicos identificaron niveles de protección anti-HBs, frente al 11,3% no inmune, y un 13,8% que no disponían de información. Del personal con información serológica (2306), obtuvieron porcentajes de no protección más elevadas la categoría masculina, 17,8%. Los niveles de protección fueron inversamente proporcionales según la variable edad, menor inmunidad a mayor edad. El personal no sanitario y los facultativos arrojaron niveles de protección más bajos, 36,9% y 11,1% respectivamente. CONCLUSIONES: A pesar de identificarse una inmunidad elevada, el porcentaje de no inmunizados y de ausencia de información inmunológica plantea la necesidad de implementar nuevas estrategias de comunicación dirigidas a este colectivo

OBJECTIVE: To estimate the prevalence of immunity against Hepatitis B virus among all healthcare workers linked to the Departments of Public Health in Torrevieja and Elx-Crevillent, two municipalities in the Valencian Community, Spain. Methods: Cross-sectional descriptive study of healthcare workers in two different public health departments. Once the sample was obtained, the anti-hepatitis B surface antibody (anti-HBsAb) levels were abstracted based on serological test results recorded in the workers’ medical records. Titers of anti-HBsAB ≥ 10 mlU / ml were considered as evience of immunity. The variables analyzed were classified by department, gender, age (18-34; 35-49; ≥ 50 years); professional category (physicians / nursing / other health personnel / non-health personnel); service at risk of contagion (Yes / No); immunity (≥ 10 mlU/ml, < 10 mlU/ml, missing) and systematic anti-HBs vaccination by date of birth (Yes / No). RESULTS: The study population consisted of 2674 workers. The highest proportions of workers were female (68.8%), between 35 and 49 years of age (52.8%), and employed in nursing,(32.2%). Overall, 74.9% of employees had evidence of hepatitis B immunity, 11.3% had no inmunity, and 13.8% was missing information on serology. Among those employees with serological information (n = 2306), lack of immunity was highest among males (17.8%). Protective titers were inversely proportional to age, with the lowest titers being found in the oldest age groups. Non-healthcare personnel and physicians also had lower levels of protection (36.9% and 11.1%, respectively). CONCLUSIONS: Despite identifying high levels of immunity among healthcare workers, the percentages of non-immunized employees and those lacking immunological information underscores the need to implement new communication strategies aimed at these at-risk groups

[Immunological Status against Hepatitis B among Healthcare Workers in Two Public Health Departments of the Valencian Community (Spain)]. / Estado inmunológico frente a la Hepatitis B del personal sanitario en dos departamentos de salud de la Comunidad Valenciana (España).

OBJECTIVE: To estimate the prevalence of immunity against Hepatitis B virus among all healthcare workers linked to the Departments of Public Health in Torrevieja and Elx-Crevillent,two municipalities in the Valencian Community, Spain. METHODS: Cross-sectional descriptive study of healthcare workers in two different public health departments. Once the sample was obtained, the anti-hepatitis B surface antibody (anti-HBsAb) levels were abstracted based on serological test results recorded in the workers' medical records. Titers of anti-HBsAB ≥10mlU / ml were considered as evience of immunity. The variables analyzed were classified by department, gender, age (18-34; 35-49;≥50 years); professional category (physicians / nursing / other health personnel / nonhealth personnel); service at risk of contagion (Yes / No); immunity (≥10mlU/ml, 〈10mlU/ml,missing) and systematic anti-HBs vaccination by date of birth (Yes / No). RESULTS: The study population consisted of 2674 workers. The highest proportions of workers were female(68.8%), between 35 and 49 years of age (52.8%), and employed in nursing,(32.2%). Overall, 74.9% of employees had evidence of hepatitis B immunity, 11.3% had no inmunity, and 13.8% was missing information on serology. Among those employees with serological information (n=2306), lack of immunity was highest among males (17.8%).Protective titers were inversely proportional to age, with the lowest titers being found in the oldest age groups. Non-healthcare personnel and physicians also had lower levels of protection (36.9% and 11.1%, respectively). CONCLUSIONS: Despite identifying high levels of immunity among healthcare workers, the percentages of non-immunized employees and those lacking immunological information underscores the need to implement new communication strategies aimed at these at-risk groups.

OBJETIVO: Estimar la prevalencia de inmunización frente al virus de la Hepatitis B del personal sanitario, vinculado a los Departamentos de Salud de Torrevieja y Elche-Crevillente, de la Comunidad Valenciana. MÉTODOS: Estudio descriptivo transversal en todos los trabajadores sanitarios de dos departamentos de Salud. Obtenida la muestra se identificó los niveles de anticuerpos de superficie del virus de la Hepatitis B a través de los resultados serológicos ubicados en las historias clínicas. Se consideró inmunizado a títulos de anti-HBs ≥10mlU/ml. Las variablesanalizadas fueron categorizadas según: Departamento; Género; Edad (18-34; 35-49; >50años); categoría profesional (facultativos/Enfermería/Otro personal sanitario/Personal no sanitario); Servicio riesgo contagio (Si/No); Inmunidad (≥10mlU/ml / 〈10mlU/ml / No Dato) y Vacunacion sistemática anti-HBs según fecha nacimiento (Si/No). RESULTADOS: El personal estudiado ascendió a 2674. Predominó el género femenino 68,8%, el grupo de edad 35-49 años, 52,8%, y la categoría profesional de Enfermería, 32,2%. Un 74,9% de los resultados serológicos identificaron niveles de protección anti-HBs, frente al 11,3% no inmune, y un 13,8% que no disponían de información. Del personal con información serológica (2306), obtuvieron porcentajes de no protección más elevadas la categoría masculina, 17,8%. Los niveles de protección fueron inversamente proporcionales según la variable edad, menor inmunidad a mayor edad. El personal no sanitario y los facultativosarrojaron niveles de protección más bajos, 36,9% y 11,1% respectivamente. CONCLUSIONES: A pesar de identificarse una inmunidad elevada, el porcentaje de no inmunizadosy de ausencia de información inmunológica plantea la necesidad de implementar nuevas estrategias de comunicación dirigidas a este colectivo.

Tracking the Light-Induced Excited-State Dynamics and Structural Configurations of an Extraordinarily Long-Lived Metastable State at Room Temperature.

Time-resolved X-ray (Tr-XAS) and optical transient absorption (OTA) spectroscopy on the pico-microsecond timescale coupled with density functional theory calculations are applied to study the light-induced spin crossover processes of a Fe-based macrocyclic complex in solution. Tr-XAS analysis after light illumination shows the formation of a seven-coordinated high-spin quintet metastable state, which relaxes to a six-coordinated high-spin configuration before decaying to the ground state. Kinetic analysis of the macrocyclic complex reveals an unprecedented long-lived decay lifetime of approximately 42.6 µs. Comparative studies with a non-macrocyclic counterpart illustrate a significantly shortened approximately 568-fold decay lifetime of about 75 ns, and highlight the importance of the ligand arrangement in stabilizing the reactivity of the excited state. Lastly, OTA analysis shows the seven-coordinated high-spin state to be formed within approximately 6.2 ps. These findings provide a complete understanding of the spin crossover reaction and relaxation pathways of the macrocyclic complex, and reveal the importance of a flexible coordination environment for their rational design.

Mesenchymal stem cell's secretome promotes selective enrichment of cancer stem-like cells with specific cytogenetic profile.

Cancer stem cells (CSCs) are responsible for tumor initiation, metastasis and cancer recurrence, however the involvement of microenvironment is crucial. Here, we have analyzed how human mesenchymal stem cells (MSCs)-derived conditioned medium (CM) affect colon and melanoma CSCs enrichment and maintenance. Our results strongly suggest that the secretome of CM-MSCs selects and maintains subpopulations with high expression of CSCs markers and ALDH1 activity, low proliferation rates with G1 phase arrest, and notably retain in vivo these properties. Cytogenetic analyses indicated that CM-cultured cells contain alterations in chromosome 17 (17q25). Subsequent SKY-FISH analyses suggested that genes located in 17q25 might be involved in stem-cell maintenance. The characterization of secreted proteins present in CM-MSCs revealed that four cytokines and seven growth factors are directly linked to the CSCs enrichment reported in this study. Further analyses revealed that the combination of just IL6 and HGF is enough to provide cancer cells with better stemness properties. In conclusion, this study demonstrates how specific chromosomal alterations present in CSCs subpopulations might represent an advantage for their in vitro maintenance and in vivo stemness properties.

Human CD6 Down-Modulation following T-Cell Activation Compromises Lymphocyte Survival and Proliferative Responses.

Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen-presenting cells and likely modulating T-cell receptor (TCR) signaling. Here, we show that in vitro activation of human T cells under different TCR-ligation conditions leads to surface downregulation of CD6 expression. This phenomenon was (i) concomitant to increased levels of soluble CD6 (sCD6) in culture supernatants, (ii) partially reverted by protease inhibitors, (iii) not associated to CD6 mRNA down-regulation, and (iv) reversible by stimulus removal. CD6 down-modulation inversely correlated with the upregulation of CD25 in both FoxP3- (Tact) and FoxP3+ (Treg) T-cell subsets. Furthermore, ex vivo analysis of peripheral CD4+ and CD8+ T cells with activated (CD25+) or effector memory (effector memory T cell, CD45RA-CCR7-) phenotype present lower CD6 levels than their naïve or central memory (central memory T cell, CD45RA-CCR7+) counterparts. CD6lo/- T cells resulting from in vitro T-cell activation show higher apoptosis and lower proliferation levels than CD6hi T cells, supporting the relevance of CD6 in the induction of proper T-cell proliferative responses and resistance to apoptosis. Accordingly, CD6 transfectants also showed higher viability when exposed to TCR-independent apoptosis-inducing conditions in comparison with untransfected cells. Taken together, these results provide insight into the origin of sCD6 and the previously reported circulating CD6-negative T-cell subset in humans, as well as into the functional consequences of CD6 down-modulation on ongoing T-cell responses, which includes sensitization to apoptotic events and attenuation of T-cell proliferative responses.

Protective Effects of Human and Mouse Soluble Scavenger-Like CD6 Lymphocyte Receptor in a Lethal Model of Polymicrobial Sepsis.

Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic components from Gram-positive and -negative bacteria and shows time- and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold standard antibiotics, in a lethal model of polymicrobial sepsis. To this end, C57BL/6 mice undergoing high-grade septic shock induced by cecal ligation and puncture (CLP; ≥90% lethality) were infused via the intraperitoneal (i.p.) or intravenous (i.v.) route with shCD6 at different doses and time points, either alone or in combination with imipenem/cilastatin (I/C) at a dose of 33 mg/kg of body weight every 8 h. Significantly reduced mortality and proinflammatory cytokine levels were observed by i.p. infusion of a single shCD6 dose (1.25 mg/kg) 1 h pre- or post-CLP. When using the i.v. route, mice survival was significantly extended by starting shCD6 infusion at later time points post-CLP (up to 6 h after CLP). Significant adjunctive effects on mouse survival were observed by i.p. or i.v. infusion of shCD6 in combination with i.p. I/C post-CLP. Similar results were obtained in mice expressing high sustained levels (5 to 10 µg/ml) of mouse sCD6 in serum by means of transduction with hepatotropic adeno-associated virus (AAV). Taken together, the data support the conserved antibacterial effects of human and mouse sCD6 and their use as adjunctive therapy in experimental models of complex and severe polymicrobial sepsis.

First-in-class inhibitor of the T cell receptor for the treatment of autoimmune diseases.

Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding concomitant opportunistic infections. Antigen binding to the T cell receptor (TCR) triggers the recruitment of the cytosolic adaptor protein Nck to a proline-rich sequence in the cytoplasmic tail of the TCR's CD3ε subunit. Through virtual screening and using combinatorial chemistry, we have generated an orally available, low-molecular weight inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC50 (median inhibitory concentration) ~1 nM. By modulating TCR signaling, the inhibitor prevented the development of psoriasis and asthma and, furthermore, exerted a long-lasting therapeutic effect in a model of autoimmune encephalomyelitis. However, it did not prevent the generation of a protective memory response against a mouse pathogen, suggesting that the compound might not exert its effects through immunosuppression. These results suggest that inhibiting an immediate TCR signal has promise for treating a broad spectrum of human T cell-mediated autoimmune and inflammatory diseases.

Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells.

BACKGROUND: Around 20%-30% of breast cancers overexpress the proto-oncogene human epidermal growth receptor 2 (HER2), and they are characterized by being very invasive. Therefore, many current studies are focused on testing new therapies against tumors that overexpress this receptor. In particular, there exists major interest in new strategies to fight breast cancer resistant to trastuzumab (Tmab), a humanized antibody that binds specifically to HER2 interfering with its mitogenic signaling. Our team has previously developed immunostimulating complexes (ISCOMs) as nanocapsules functionalized with lipid vinyl sulfones, which can incorporate protein A and bind to G immunoglobulins that makes them very flexible nanocarriers. METHODS AND RESULTS: The aim of this in vitro study was to synthesize and evaluate a drug delivery system based on protein A-functionalized ISCOMs to target HER2-overexpressing cells. We describe the preparation of ISCOMs, the loading with the drugs doxorubicin and paclitaxel, the binding of ISCOMs to alkyl vinyl sulfone-protein A, the coupling of Tmab, and the evaluation in both HER2-overexpressing breast cancer cells (HCC1954) and non-overexpressing cells (MCF-7) by flow cytometry and fluorescence microscopy. Results show that the uptake is dependent on the level of overexpression of HER2, and the analysis of the cell viability reveals that targeted drugs are selective toward HCC1954, whereas MCF-7 cells remain unaffected. CONCLUSION: Protein A-functionalized ISCOMs are versatile carriers that can be coupled to antibodies that act as targeting agents to deliver drugs. When coupling to Tmab and loading with paclitaxel or doxorubicin, they become efficient vehicles for the selective delivery of the drug to Tmab-resistant HER2-overexpressing breast cancer cells. These nanoparticles may pave the way for the development of novel therapies for poor prognosis resistant patients.

Meroxest improves the prognosis of immunocompetent C57BL/6 mice with allografts of E0771 mouse breast tumor cells.

INTRODUCTION: Recently, we have reported the antitumor properties of a new family of synthetic merosesquiterpenes, among which meroxest is highlighted, since it has high activity and specificity for ER+ breast cancer cells. In this paper, we characterize allografts of ER+ E0771 mouse breast tumor cells in immunocompetent C57BL/6 mice, and also analyze the effect of meroxest on the prognosis of the disease. MATERIAL AND METHODS: Twenty female C57BL/6 mice were injected with 106 E0771 cells. Once the tumors reached the appropriate size, the mice were divided into two groups, one control and another treated orally with 15 mg/kg of meroxest. After 20 days, tumor samples were taken for histopathological study and for determination of the expression of the prognostic markers Ki67 and vascular endothelial growth factor (VEGF) by immunofluorescence. RESULTS: In sections stained with hematoxylin-eosin, we observed that tumors have a well-defined capsule enclosing E0771 tumor cells. The central area of tumors contains necrotic regions with leukocyte infiltration. Meroxest treatment significantly reduces tumor size (68%, p < 0.05), induces changes in its structure, decreases the degree of leukocyte infiltration, and significantly reduces the expression of Ki67 (33%, p < 0.05) and VEGF (82%, p < 0.05). CONCLUSIONS: Meroxest improves the prognosis of mice since it reduces leukocyte infiltration, and decreases the expression of Ki67 and VEGF markers. Consequently, the merosesquiterpene could become a useful antiangiogenic drug in the treatment of breast cancer. These results encourage us to deepen the study of meroxest, in order to find more evidence that supports the convenience of its evaluation in a clinical study or trial.

Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results.

The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency.

Pattern Recognition by CD6: A Scavenger-Like Lymphocyte Receptor.

CD6, one of the first antigens to be identified on T cells, is a membrane glycoprotein that physically associates with the antigen receptor complex. Because of this, its main function seems to involve the modulation of TCR-mediated signaling pathways. However, growing evidence indicates that this ancient and conserved scavenger-like receptor may also play a role as pattern recognition receptor (PRR), similar to other members of the scavenger receptor cysteine rich superfamily (SRCR-SF). Here, we discuss the functional interactions of CD6 with microbe- and damage-associated signals and the potential use of soluble forms of CD6 in the therapeutic treatment of bacterial infections, in particular multi-drug resistant bacterial strains. Importantly, microbe recognition by CD6 may also have functional consequences on T cell activation and differentiation, which remain to be explored.

Pattern of soluble CD5 and CD6 lymphocyte receptors in critically ill patients with septic syndromes.

PURPOSE: Soluble forms of CD5 and CD6 lymphocyte surface receptors (sCD5 and sCD6) are molecules that seem to prevent experimental sepsis when exogenously administered. The aim of this study was to assess sCD5 and sCD6 levels in patients with septic syndromes. MATERIALS AND METHODS: The study population consisted of 218 patients admitted to the medical intensive care unit (ICU) presenting either septic syndromes or noninfectious systemic inflammatory response syndrome at admission or within the first 48 hours. The sCD5 and sCD6 levels were analyzed by sandwich enzyme-linked immunosorbent assay. RESULTS: Almost 50% of the patients had undetectable levels of sCD5 or sCD6, with no differences in clinical or biological variables with detectable patients. There was a correlation between the delta Sequential Organ Failure Assessment score and both sCD6 and sCD5 levels in all groups. Patients with sCD5 or sCD6 levels greater than 1500 ng/mL presented a higher in-ICU mortality (P < .05). Logistic regression analysis showed that increased sCD6 levels were associated with an increased risk of in-ICU mortality. CONCLUSIONS: Levels of sCD5 and sCD6 in critically ill patients with systemic inflammatory response syndrome present a high variation and an elevated proportion of undetectability. Levels of sCD6 are associated with an increased risk of mortality in these patients.

First enantiospecific syntheses of marine merosesquiterpenes neopetrosiquinones a and B: evaluation of biological activity.

The first enantiospecific syntheses of neopetrosiquinones A (6) and B (7), two merosesquiterpenes isolated from the deep-water sponge Neopetrosia cf. proxima, from the labdane diterpene trans-communic acid (10) have been achieved. A key step of the synthetic sequence is the simultaneous aromatization of the C ring and the benzylic oxidation on C-7 of an advanced intermediate, mediated by the oxygen-DDQ system. The in vitro antiproliferative activities of neopetrosiquinone B (7) and of the synthetic intermediates 8 and 9 against human breast (MCF-7), lung (A-549), and colon (T-84) tumor cell lines have been assayed. The most potent was compound 9 (IC50 = 4.1 µM), which was twice as active as natural compound 7 (IC50 = 8.3 µM) against A-549 cells. In addition, the treatment with these compounds resulted in an induction of apoptosis. These findings indicate that the terpene benzoquinones reported here might be potentially useful as anticancer agents.

O2 adsorption dependent photoluminescence emission from metal oxide nanoparticles.

Optical properties of metal oxide nanoparticles are subject to synthesis related defects and impurities. Using photoluminescence spectroscopy and UV diffuse reflectance in conjunction with Auger electron spectroscopic surface analysis we investigated the effect of surface composition and oxygen adsorption on the photoluminescence properties of vapor phase grown ZnO and MgO nanoparticles. On hydroxylated MgO nanoparticles as a reference system, intense photoluminescence features exclusively originate from surface excitons, the radiative deactivation of which results in collisional quenching in an O2 atmosphere. Conversely, on as-prepared ZnO nanoparticles a broad yellow emission feature centered at hνEm = 2.1 eV exhibits an O2 induced intensity increase. Attributed to oxygen interstitials as recombination centers this enhancement effect originates from adsorbate-induced band bending, which is pertinent to the photoluminescence active region of the nanoparticles. Annealing induced trends in the optical properties of the two prototypical metal oxide nanoparticle systems, ZnO and MgO, are explained by changes in the surface composition and underline that particle surface and interface changes that result from handling and processing of nanoparticles critically affect luminescence.