Identification of prognostic factors for survival in patients with metastatic gastric adenocarcinoma in a Mexican population.

INTRODUCTION AND AIMS: Gastric adenocarcinoma is among the high-ranking tumors, with respect to frequency and mortality, worldwide. The inflammatory process and immune system activity are associated with oncologic control. Our aim was to identify whether the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and other variables are prognostic factors for survival in patients with metastatic gastric cancer in a Mexican population. MATERIAL AND METHODS: Patients diagnosed with metastatic gastric adenocarcinoma, hospitalized within the time frame of December 2011 to 2021, were analyzed. The NLR, PLR, and albumin and hemoglobin levels obtained from blood samples were calculated. Functional status (ECOG and Karnofsky), sex, histology, and the presence of signet ring cells were also considered possible prognostic factors. Each factor's prognostic value for overall survival was determined through univariate and multivariate analyses. RESULTS: The study included 956 patients diagnosed with metastatic gastric cancer, of whom 494 (51.7%) were men and 462 (48.3%) were women. The main histologic finding was diffuse adenocarcinoma (n = 619, 64.7%), followed by intestinal adenocarcinoma (n = 293, 30.6%), and the presence of signet ring cells was found in 659 (68.9%) patients. Diagnostic laparoscopy was performed on 238 patients (24.9%) to confirm peritoneal carcinomatosis. The multivariate analysis showed that an NLR above 3.2 (HR 1.51, 95% CI 1.27-1.8; p < 0.001), albumin below 3.5 g/dl (HR 1.25, CI 1.06-1.47; p = 0.006), and an ECOG performance status of 2 or higher (HR 1.39, CI 1.10-1.76; p = 0.005) were independent factors that predicted a lower survival rate, whereas a Karnofsky score above 70% (HR 0.69, CI 0.53-0.91; p = 0.008) was associated with a better survival rate. Lastly, the PLR was not statistically significant in the multivariate analysis. CONCLUSIONS: The NLR, nutritional status assessed through albumin measurement, and functional status can act as independent prognostic survival factors in hospitalized Mexican patients diagnosed with metastatic gastric adenocarcinoma and be taken into account during therapeutic decision-making.

TCNQ molecular semiconductor of the Cu(II)TAAB macrocycle: Optical and electrical properties.

The present study reports the doping of a semiconducting molecular material through the formation of hydrogen bonds between the macrocycle Cu(II)(TAAB) and the electronic acceptor TCNQ. According to density functional theory (DFT) calculations and electron paramagnetic resonance (EPR) analysis, the doped compound has the shape of a distorted square pyramid, with four nitrogen atoms in the equatorial position and the apical oxygen atom from the water ligands. These water molecules can generate strong hydrogen bonds with TCNQ and the TAAB metallic complex. Thin films of copper molecular material were obtained through high vacuum evaporation and were structurally characterized by IR spectroscopy, EPR and scanning electron microscopy (SEM). Additionally, the absorption coefficient (α) and photon energy (hν) were calculated from UV-vis spectroscopy and used to determine the optical activation energy in each film, from which its semiconducting behavior was established. An important aspect to consider is that the presence of hydrogen bonds is essential to establish the semiconducting nature of these species; this chemical behavior, as well as the resulting electronic mobility, have been studied by DFT theoretical calculations, which reinforce the experimental conclusion of a relationship between Cu(II)TAAB and TCNQ moieties generated by a weak bond. Finally, I-V characteristics have been obtained from a glass/ITO/doped molecular semiconductor/Ag device using Ag and ITO electrodes. Results for the copper-based device show that, at low voltages, the conduction process is of an ohmic nature while, at higher voltages, space-charge-limited current (SCLC) is found. It is highly probable that the doping effect in TCNQ favors electronic transport due to the formation of conduction channels caused by dopant-favored anisotropy.

Thermoluminescent characteristics of LiF:Mg, Cu, P and CaSO4:Dy for low dose measurement.

Thermoluminescence (TL) characteristics for LiF:Mg, Cu, P, and CaSO4:Dy under the homogeneous field of X-ray beams of diagnostic irradiation and its verification using thermoluminescence dosimetry are presented. The irradiation were performed utilizing a conventional X-ray equipment installed at the Hospital Juárez Norte of México. Different thermoluminescence characteristics of two material were studied, such as batch homogeneity, glow curve, linearity, detection threshold, reproducibility, relative sensitivity and fading. Materials were calibrated in terms of absorbed dose to the standard calibration distance and they were positioned in a generic phantom. The dose analysis, verification and comparison with the measurements obtained by the TLD-100 were performed. Results indicate that the dosimetric peak appears at 202°C and 277.5°C for LiF:Mg, Cu, P and CaSO4:Dy, respectively. TL response as a function of X-ray dose showed a linearity behavior in the very low dose range for all materials. However, the TLD-100 is not accurate for measurements below 4mGy. CaSO4:Dy is 80% more sensitive than TLD-100 and it show the lowest detection threshold, whereas LiF:Mg, Cu, P is 60% more sensitive than TLD-100. All materials showed very good repeatability. Fading for a period of one month at room temperature showed low fading LiF:Mg, Cu, P, medium and high for TLD-100 and CaSO4:Dy. The results suggest that CaSO4:Dy and LiF:Mg, Cu, P are suitable for measurements at low doses used in radiodiagnostic.

Thermoluminescent dosimeters for low dose X-ray measurements.

The response of TLD-100, CaSO4:Dy and LiF:Mg,Cu,P for a range of X-ray low dose was measured. For calibration, the TLDs were arranged at the center of the X-ray field. The dose output of the X-ray machine was determined using an ACCU-Gold. All dosimeters were exposed at the available air kerma values of 14.69 mGy within a field 10×10 cm(2) at 80 cm of SSD. Results of LiF:Mg,Cu,P X-ray irradiated showed 4.8 times higher sensitivity than TLD-100. Meanwhile, TL response of CaSO4:Dy exposed at the same dose was 5.6 time higher than TLD-100. Experimental results show for low dose X-ray measurements a better linearity for LiF:Mg,Cu,P compared with that of TLD-100. CaSO4:Dy showed a linearity from 0.1 to 60 mGy.

Thermoluminescent characterization of HfO2:Tb3+ synthesized by hydrothermal route.

Thermo and photoluminescent properties of nanoparticles (NPs) of hafnium oxide (HfO2), both intrinsic and doped with terbium (Tb(3+)) are reported. The NPs of HfO2 were synthesized by hydrothermal route, using hafnium tetrachloride (HfCl4) and terbium chloride hexahydrated (TbCl3∙6H2O) as precursors and sodium hydroxide (NaOH) to adjust the pH. Deionized water was used as solvent in all cases. The synthesis was carried out at different dopant concentrations from 0 to 20 at% of terbium with respect to the amount of hafnium in the precursor solution. The temperature of hydrothermal treatment was 200 °C and 80 min of reaction time. X-ray diffraction results show that at terbium concentrations higher than 15 at% the HfO2 nanoparticles have a crystalline structure corresponding to the tetragonal phase. Thermoluminescent (TL) characterization was performed after 5 min irradiation of the samples with ultraviolet light of 200 nm wavelength. The highest TL emission was observed on samples with 7 at% of Tb, with the TL peak centered at 128 °C. Thermoluminescence analysis shows behavior associated with second-order kinetics with activation energy of 0.49 eV. Photoluminescent spectrum present the characteristics (5)D4→(7)FJ (J=3-6) terbium ion electronic transitions lines centered on 489 nm, 543 nm, 584 nm and 622 nm.

Determinación de stock de medicamentos y productos médicos para tratamiento inicial en desastres utilizando la tecnica DELPHI en un Hospital del interior de la Provincia de Córdoba (Argentina) / Drugs and medical products stock determination for initial treatment in disaster situations using delphi technique in a hospital in the interior of the province of Cordoba (Argentina) / Determinação do estoque de medicamentos eprodutos médicos para tratamento inicial emdesastres empregando a técnica delphi em umhospital do interior da província de Córdoba (Argentina)

El objetivo de este trabajo fue determinar el stock de medicamentos y productos médicos para el tratamiento inicial de víctimas en masa en un hospital de la provincia de Córdoba (Argentina).Se utilizó la Técnica Delphi como método de consenso. Se solicitó la participación de 13 profesionales entre médicos y enfermeras del Hospital Dr. Arturo U. Illia de la ciudad de Alta Gracia, coordinados por una farmacéutica. Se realizaron 3 cuestionarios por medio de los cuales se arribó a la selección de los insumos necesarios para la atención de víctimas en masa para un plazo de 48 horas.Se determinaron dos listados finales con 25 medicamentos y 25 productos médicos, respectivamente.La utilización de esta técnica en la mencionada selección, agilizó el consenso en la toma de decisiones respecto a la inclusión de los insumos en cuestión.

The objective of this work was to determine the stock of drugs and medical products for the initial treatment of mass casualties at a hospital in the province of Córdoba (Argentina). Delphi Technique was used as the consensus method. Thirteen practitioners including physicians and nurses from Dr. Arturo U. Illia Hospital, in the city of Alta Gracia, were requested to participate, coordinated by a pharmacist. Three questionnaires were produced to come to a selection of the necessary products for mass casualty management during a 48-hour period. Two final lists were made with 25 drugs and 25 medical products, respectively. The use of this technique for the above mentioned selection accelerated consensus in decision making regarding the inclusion of the items in question

Determinación de stock de medicamentos y productos médicos para tratamiento inicial en desastres utilizando la tecnica DELPHI en un Hospital del interior de la Provincia de Córdoba (Argentina) / Drugs and medical products stock determination for initial treatment in disaster situations using delphi technique in a hospital in the interior of the province of Cordoba (Argentina) / DeterminaþÒo do estoque de medicamentos eprodutos médicos para tratamento inicial emdesastres empregando a técnica delphi em umhospital do interior da província de Córdoba (Argentina)

El objetivo de este trabajo fue determinar el stock de medicamentos y productos médicos para el tratamiento inicial de víctimas en masa en un hospital de la provincia de Córdoba (Argentina).Se utilizó la Técnica Delphi como método de consenso. Se solicitó la participación de 13 profesionales entre médicos y enfermeras del Hospital Dr. Arturo U. Illia de la ciudad de Alta Gracia, coordinados por una farmacéutica. Se realizaron 3 cuestionarios por medio de los cuales se arribó a la selección de los insumos necesarios para la atención de víctimas en masa para un plazo de 48 horas.Se determinaron dos listados finales con 25 medicamentos y 25 productos médicos, respectivamente.La utilización de esta técnica en la mencionada selección, agilizó el consenso en la toma de decisiones respecto a la inclusión de los insumos en cuestión.(AU)

The objective of this work was to determine the stock of drugs and medical products for the initial treatment of mass casualties at a hospital in the province of Córdoba (Argentina). Delphi Technique was used as the consensus method. Thirteen practitioners including physicians and nurses from Dr. Arturo U. Illia Hospital, in the city of Alta Gracia, were requested to participate, coordinated by a pharmacist. Three questionnaires were produced to come to a selection of the necessary products for mass casualty management during a 48-hour period. Two final lists were made with 25 drugs and 25 medical products, respectively. The use of this technique for the above mentioned selection accelerated consensus in decision making regarding the inclusion of the items in question(AU)

Improved nonviral cancer suicide gene therapy using survivin promoter-driven mutant Bax.

Suicide gene vectors are being developed in many laboratories as an attractive approach to cancer therapy. However, the development of these therapies is hampered by safety concerns and limitations of efficacy. The use of tumor-specific promoters, such as survivin promoter, can provide much needed specificity to target tumor cells. However, the expression levels from these promoters is often suboptimal and hence it is imperative to enhance the activity of the cytotoxic gene of interest. We tested apoptotic activity of several mutants of proapoptotic gene bax that constitutively translocate to the mitochondria and induce apoptosis. One of these mutants with deletion of serine at position S184 (S184del) was found to be most active and showed significant antitumor activity when expressed by the survivin promoter. In vitro testing shows that this vector (Sur-BaxS184del) induces cell killing in a variety of tumor cell lines of different origin with significantly higher efficacy than wild-type bax (Sur-BaxWT). The increase in cytotoxicity was a result of enhanced induction of apoptosis in tumor cells. In contrast to cytomegalovirus (CMV) promoter-driven bax (CMV-Bax), Sur-BaxS184del caused minimum toxicity in normal human dermal fibroblasts validating its specificity and safety. In a mouse tumor model (DA-3, murine breast cancer cells), we show that intratumoral injection of Sur-BaxS184del resulted in tumor growth retardation to the same level as CMV-Bax. This study highlights the effectiveness of using bax mutants in combination with survivin promoter for tumor-targeted suicide gene therapy in a nonviral vector.

Bypass gástrico convencional y laparoscópico en el tratamiento de la obsesidad mórbida. Evaluación comparativa de la calidad de vida por medio del Test de Baros / Laparoscopic or open gstric bypass for the treatment of morbid obesity. Comparative bariatric evaluation of the quality of life

La obesidad mórbida representa un problema mundial cuya prevalencia se encuentra en aumento, sólo el enfoque quirúrgico ha demostrado resultados persistentes en cuanto a la pérdida de peso de manera permanente. Objetivo: evaluación del impacto social de la pérdida de peso en el paciente obeso posterior al tratamiento quirúrgico por medio de un bypass laparoscópico o convencional y análisis de costos operativos.

Morbid obesity represents a health-related problem rising all over the world, just the surgical management has demonstrted persistent and constant outcome in weight lose. Objective: Evaluations of the social impact and operative cost in weight lose obese morbid patients after laparoscopic or open gastric bypass.

Bypass gástrico convencional y laparoscópico en el tratamiento de la obsesidad mórbida. Evaluación comparativa de la calidad de vida por medio del Test de Baros / Laparoscopic or open gstric bypass for the treatment of morbid obesity. Comparative bariatric evaluation of the quality of life

La obesidad mórbida representa un problema mundial cuya prevalencia se encuentra en aumento, sólo el enfoque quirúrgico ha demostrado resultados persistentes en cuanto a la pérdida de peso de manera permanente. Objetivo: evaluación del impacto social de la pérdida de peso en el paciente obeso posterior al tratamiento quirúrgico por medio de un bypass laparoscópico o convencional y análisis de costos operativos.(AU)

Morbid obesity represents a health-related problem rising all over the world, just the surgical management has demonstrted persistent and constant outcome in weight lose. Objective: Evaluations of the social impact and operative cost in weight lose obese morbid patients after laparoscopic or open gastric bypass.(AU)

Theoretical study of vanadium oxides interaction with Y-zeolite.

A current problem about oils and feedstock in fluid catalytic cracking (FCC) is the continuous cumulative deposition of metal contaminants on the catalyst, resulting in important modifications of its properties. Vanadium plays a detrimental role on the catalyst components because enhances the destruction of the Y-zeolite structure during regeneration stage when it is exposed by steam and oxygen at high temperatures. Knowledge of the mechanism interaction of vanadium with the catalyst is important to improve FCC performance. Quantum Molecular Dynamics calculations were done introducing the VO, V2O3, VO2 or V2O5 molecules at the center of a Y-zeolite ring simulating regeneration conditions. The results indicate that the principal reaction is carried out among the zeolite and the vanadium atoms of molecules. This happens, when interaction is presented, since the loss of a hydrogen atom of the active place causes high degree of oxygen reactivity.

¿Se debe formar el residente de Pediatría en Atención Primaria? ¿Por qué? Encuesta a pediatras y residentes de Valencia / No disponible

Introducción y objetivos: considerando que el residente de Pediatría no se forma en puericulturani en prevención y promoción de salud del niño sano en centros de Atención PediátricaPrimaria, ni para el tratamiento del niño que no precisa atención hospitalaria, se intentasaber si el residente debe formarse en Atención Primaria.Material y métodos: para ello se distribuyó una encuesta anónima dirigida a todos lospediatras que prestan la Atención Primaria en la ciudad de Valencia, a todos los pediatras delHospital La Fe y a todos los residentes de Pediatría de dicho hospital. Se preguntó: ¿Creesque el residente de Pediatría debe rotar –también– por un centro de Atención Primaria acreditadopara completar su formación? Y ¿por qué?Resultados: se obtuvo un porcentaje de respuesta del 44,7%. El 86% respondió sí, el13% no y el 1% en blanco. Dijeron sí el 90% de los pediatras (95% de Primaria y 83% dehospital) y el 50% de los residentes. Los encuestados respondieron a la segunda parte de lapregunta y aportaron su opinión respecto a los motivos a favor de la rotación en AtenciónPediátrica Primaria; el 29% aportó ideas respecto al programa de formación del residente. El13% que opinó que no debe rotar justificó su opinión y aportó ideas para la formación delresidente. Conclusiones: el 86% de encuestados opina que el residente de Pediatría debe rotar porAtención Primaria para completar su formación y el 17% reclama alargar a más de cuatro añosla especialidad de Pediatría

Introduction and objectives: considering that the resident physician in the specialty ofpaediatrics in Valencia never trains in Paediatric Primary Care centres and that he does notreceive any preparation in child care nor in aspects as preventive care and promotion of goodhabits in healthy children or the treatment of ill children who do not need hospitalization,our intention is to find out if residents should be trained in Paediatric Primary Care, accordingto the opinion of paediatricians and residents in paediatrics.Material and methods: for this reason, an anonymous survey was carried out directed toall paediatricians in Primary Care in the city of Valencia and to all paediatricians and residentsin paediatrics who practise hospital care in the Hospital La Fe. The questions were: Doyou think that a paediatric resident should train –additionally– in an accredited primary healthcare center in order to complete his training? Why?Results: a percentage of 44.7% answered. Eighty-six per cent answered yes, 13% no and1% blank. Affirmative responses were from 90% of the paediatricians (95% primary carepaediatricians and 85% hospital care paediatricians) and 50% of the residents. Those surveyedresponded to the second part of the question giving their opinion on the motives in favourof Paediatric Primary Care training. 29% offered ideas for the resident training program,the 13% against Paediatric Primary Care training, that justified with their opinions.Conclusions: 86% say the resident should be trained in Paediatric Primary Care and17% demand more than four years’ training in Paediatrics

[Nosocomial infection by multiresistant pathogens during one year in a secondary hospital: clinical an epidemiological analysis]. / Infección nosocomial por gérmenes multirresistentes durante 1 año en un hospital de segundo nivel: análisis clínico y microbiológico.

BACKGROUND: Currently growing medical and social significance of nosocomial infection by multiresistant pathogens (NIMP) prompted us to establish its incidence, nosology, presenting forms in admission areas, and mortality in a secondary hospital, Lleida (Spain). METHOD: For that purpose, we analyzed the first year experience of a unit for the control of nosocomial infection (NI) created in our hospital. From January to December 2000, 79 patients with a NIMP admitted to the University Hospital Arnau de Vilanova entered in this prospective, descriptive study. RESULTS: The overall annual incidence of NIMP was 4.0 per 103 patients admitted. Acinetobacter baumannii showed the highest individual rate of incidence, particularly, at the Intensive Care Unit (15.4 per 103 patients admitted; p < 0.001). By nosologies, infection prevailed over colonization (69.6% vs 30.4%; p < 0.001). Mean hospital stay length increased in colonized patients (38.9 days). Finally, overall mortality was high (29.1%); again, A. baumannii was the agent most frequently detected in death cases (66.6%; p < 0.001). CONCLUSIONS: Surveillance and control measures are required for the prevention of NIMP. Incidence studies how this, can be useful to create a database to establish the distribution and occurrence of NI, including the detection of multiresistant pathogen outbreaks.

Infección nosocomial por gérmenes multirresistentes durante 1 año en un hospital de segundo nivel: análisis clínico y microbiológico / Nosocomial infection by multiresistant pathogens during one year in a secondary hospital: clinical and epidemiological analysis

Fundamento: Dada la gran relevancia actual, médica y social, de la infección nosocomial por gérmenes multirresistentes (INGM), se pretendió determinar su incidencia, nosología, formas de presentación en las áreas de ingreso y mortalidad en un hospital de 2º nivel en Lleida (España). Método: Se utilizó la experiencia de una unidad para el control de la Infección Nosocomial (IN), en su primer año de funcionamiento en este hospital. Por medio de la unidad, se practicó un estudio descriptivo prospectivo sobre todos los pacientes ingresados, en el Hospital Universitario Arnau de Vilanova, entre enero y diciembre de 2000 en los que se detectó una INGM. Resultados: En total fueron 79 pacientes los que presentaron una INGM. La tasa de incidencia global anual de INGM fue de 4,0 por 103 pacientes ingresados. A. baumannii fue el germen que obtuvo la tasa de incidencia individual más elevada, y en especial en la Unidad de Cuidados Intensivos (15,4 por 103 pacientes ingresados; p < 0,001). Por nosologías,la infección predominó sobre la colonización (69,6 frente 30,4%; p < 0,001). En general, se observó una estancia media más prolongada en los pacientes colonizados 38,9 días. Por último, la mortalidad total fue elevada (29,1%), destacando de nuevo A. baumannii, como el agente más frecuentemente detectado en los pacientes que fallecieron (66,6%; p < 0,001). Conclusiones: En la prevención de la INGM son necesarias medidas de vigilancia y control. Los estudios de incidencia como éste, pueden ser útiles a la hora de establecer una base de datos con la que observar la distribución y ocurrencia de la IN, incluyendo la detección de brotes epidémicos por gérmenes multirresistentes

Background: Currently growing medical and social significance of nosocomial infection by multiresistant pathogens (NIMP) prompted us to establish its incidence, nosology, presenting forms in admission areas, and mortality in a secondary hospital, Lleida (Spain). Method: For that purpose, we analyzed the first year experience of a unit for the control of nosocomial infection (NI) created in our hospital. From January to December 2000, 79 patients with a NIMP admitted to the University Hospital Arnau de Vilanova entered in this prospective, descriptive study. Results: The overall annual incidence of NIMP was 4.0 per 103 patients admitted. Acinetobacter baumannii showed the highest individual rate of incidence, particularly, at the Intensive Care Unit (15.4 per 103 patients admitted; p < 0.001). By nosologies, infection prevailed over colonization (69.6% vs 30.4%; p < 0.001). Mean hospital stay length increased in colonized patients (38.9 days). Finally, overall mortality was high (29.1%); again, A. baumannii was the agent most frequently detected in death cases (66.6%; p < 0.001). Conclusions: Surveillance and control measures are required for the prevention of NIMP. Incidence studies how this, can be useful to create adatabase to establish the distribution and occurrence of NI, including the detection of multiresistant pathogen outbreaks

Electron spin resonance and electronic structure of vanadyl-porphyrin in heavy crude oils.

A study of vanadyl-porphyrin by electron spin resonance (ESR) was carried out looking for answers about the role that the central V=O ion plays when these kinds of molecules are present in heavy crude oils. The eigenvalues of the linear combination of atomic orbitals (LCAO) were obtained from the experimental values of g and parameters (ESR). The contributions to the molecular orbitals that describe the various energy levels of vanadyl ion were also obtained for the porphyrin species. The trends of the degree of covalent character of the metal-ligand bonds and the length of the vanadium-oxygen chemical bond are discussed. It is interesting to note that the Fermi contact term, K(eff), is essentially constant for all samples investigated, and it was found to be independent of the calculated electron delocalization (1 - delta(2)) and shows only little variation among the three different samples of oil. The orbital energies derived from our ESR study qualitatively agree with those predicted from MO theory for synthetic vanadyl-porphyrins.

The diverse role of chemokines in tumor progression: prospects for intervention (Review).

Chemokines, proteins chemotactic for leukocytes and non-leukocytes, have been intensively studied for their role in tumor growth and metastasis. Recent work has shown that particular chemokines may have multiple effects on tumors including promoting growth, angiogenesis, metastasis, and suppression of the immune response to cancer, while other chemokines inhibit tumor mediated angiogenesis and promote anti-tumor immune responses. Increasing biological evidence supports the hypothesis that tumor-generated chemokines provide more than simply angiogenic signals. Tumor-derived chemokines may potentially act as inhibitors of anti-tumor immune responses as well as autocrine growth factors for the tumor. The complexity and redundancy of tumor chemokine expression suggests that a single chemokine target for tumor therapy may not be appropriate. Indeed, multiple target therapy including blockade of tumor enhancing chemokines while delivering or inducing the secretion of anti-tumor chemokines is the approach that currently holds the most promise. The role of chemokines in tumor biology as well as various means of blocking chemokines in cancer models in order to develop successful therapeutic strategies will be discussed.

Eotaxin (CCL11) induces in vivo angiogenic responses by human CCR3+ endothelial cells.

Chemokines are attractants and regulators of cell activation. Several CXC family chemokine members induce angiogenesis and promote tumor growth. In contrast, the only CC chemokine, reported to play a direct role in angiogenesis is monocyte-chemotactic protein-1. Here we report that another CC chemokine, eotaxin (also known as CCL11), also induced chemotaxis of human microvascular endothelial cells. CCL11-induced chemotactic responses were comparable with those induced by monocyte-chemotactic protein-1 (CCL2), but lower than those induced by stroma-derived factor-1alpha (CXCL12) and IL-8 (CXCL8). The chemotactic activity was consistent with the expression of CCR3, the receptor for CCL11, on human microvascular endothelial cells and was inhibited by mAbs to either human CCL11 or human CCR3. CCL11 also induced the formation of blood vessels in vivo as assessed by the chick chorioallantoic membrane and Matrigel plug assays. The angiogenic response induced by CCL11 was about one-half of that induced by basic fibroblast factor, and it was accompanied by an inflammatory infiltrate, which consisted predominantly of eosinophils. Because the rat aortic sprouting assay, which is not infiltrated by eosinophils, yielded a positive response to CCL11, this angiogenic response appears to be direct and is not mediated by eosinophil products. This suggests that CCL11 may contribute to angiogenesis in conditions characterized by increased CCL11 production and eosinophil infiltration such as Hodgkin's lymphoma, nasal polyposis, endometriosis, and allergic diathesis.

A density functional study of the reactivity and stability of mixed copper complexes. Is hardness the reason?

Mixed-ligand Cu2+ ternary complexes, formed by an aromatic diimine and a second ligand with O donor atoms, show a higher than expected stability. To understand the factors affecting the stability of these systems, we performed a density functional study of [Cu(H2O)5]2+, [Cu(N-N)(H2O)3]2+, and [Cu(N-N)(O-O)H2O] (N-N is 1,10-phenanthroline, 5-nitro-1,10-phenanthroline, or 3,4,7,8-tetramethyl-1,10-phenanthroline; and O-O is oxalate). In the present study, full geometry optimization (B3LYP/3-21G**) has been performed without symmetry constraints and a comparison with some available experimental results has been made. Bond distances, equilibrium geometries, harmonic frequencies, and net atomic charges from Mulliken populations are presented. Since the principle of hard and soft acids and bases has been widely used to explain the stability of these complexes, we also calculated and analyzed the global hardness and the local softness. The results of the global hardness do not support the commonly held idea that harder acids will preferably bind to harder ligands, while softer acids will bind to softer ligands. Interestingly, local softness and electron affinity correlate well with the formation constants of these compounds and provide an explanation of the reactivity behavior. The present results may help to rationalize the stability and reactivity of these systems.

Differential expression and responsiveness of chemokine receptors (CXCR1-3) by human microvascular endothelial cells and umbilical vein endothelial cells.

The basis for the angiogenic effects of CXC chemokines such as interleukin 8 (IL-8) and for angiostatic chemokines such as interferon-inducible protein 10 (IP-10) has been difficult to assess. We recently reported, based on an RNase protection assay, that human umbilical vein endothelial cells (HUVECs) did not express detectable mRNA for the IL-8 receptors CXCR1 and CXCR2. This raised the possibility of heterogeneity of receptor expression by different endothelial cell (ECs) types. Since systemic angiogenesis induced by IL-8 would more likely involve microvessel ECs, we investigated CXC receptor expression on human microvascular dermal endothelial cells (HMECs). By confocal microscopy and immunofluorescence we observed that HMECs consistently expressed high levels of CXCR1 and CXCR4 (mean fluorescence intensity of 261+/-22.1 and 306.2+/-19, respectively) and intermediate levels of CXCR3 and CXCR2 (173.9+/-30. 2 and 156+/-30.9, respectively). In contrast, only a small proportion of HUVEC preparations expressed low levels of CXCR1, -2, and -3 (66+/-19.9; 49+/-15, and 81.4+/-17.9, respectively). However, both HMECs and HUVECs expressed equal levels of CXCR4. As expected, HMECs had more potent chemotactic responses to IL-8 than HUVECs, and this was correlated with the levels of IL-8 receptors on the ECs. Antibodies to CXCR1 and CXCR2 each had inhibitory effects on chemotaxis of HMECs to IL-8, indicating that both IL-8 receptors contributed to the migratory response of these cells toward IL-8. Assessment of the functional capacity of CXCR3 unexpectedly revealed that HMECs migrated in response to relatively higher concentrations (100-500 ng/ml) of each of the 'angiostatic' chemokines IP-10, ITAC, and MIG. Despite this, the 'angiostatic' chemokines inhibited the chemotactic response of HMECs to IL-8. IL-8 and SDF-1alpha but not IP-10 induced calcium mobilization in adherent ECs, suggesting that signaling events associated with calcium mobilization are separable from those required for chemotaxis. Taken together, our data indicated that functional differences among EC types is dependent on the level of the expression of CXC chemokine receptors. Whether this heterogeneity in receptor expression by ECs reflects distinct differentiation pathways remains to be established.