Monoclonal Antibody chP3R99 Reduces Subendothelial Retention of Atherogenic Lipoproteins in Insulin-Resistant Rats: Acute Treatment Versus Long-Term Protection as an Idiotypic Vaccine for Atherosclerosis.

BACKGROUND: Atherosclerosis is triggered by the retention of apolipoprotein B-containing lipoproteins by proteoglycans. In addition to low-density lipoprotein, remnant lipoproteins have emerged as pivotal contributors to this pathology, particularly in the context of insulin resistance and diabetes. We have previously reported antiatherogenic properties of a monoclonal antibody (chP3R99) that recognizes sulfated glycosaminoglycans on arterial proteoglycans. METHODS AND RESULTS: Solid-phase assays demonstrated that chP3R99 effectively blocked >50% lipoprotein binding to chondroitin sulfate and vascular extracellular matrix in vitro. The preperfusion of chP3R99 (competitive effect) resulted in specific antibody-arterial accumulation and reduced fluorescent lipoprotein retention by ~60% in insulin resistant JCR:LA-cp rats. This competitive reduction was dose dependent (25-250 µg/mL), effectively decreasing deposition of cholesterol associated with lipoproteins. In a 5-week vaccination study in insulin resistant rats with (200 µg subcutaneously, once a week), chP3R99 reduced arterial lipoprotein retention, and was associated with the production of antichondroitin sulfate antibodies (Ab3) able to accumulate in the arteries (dot-blot). Neither the intravenous inoculation of chP3R99 (4.5 mg/kg), nor the immunization with this antibody displayed adverse effects on lipid or glucose metabolism, insulin resistance, liver function, blood cell indices, or inflammation pathways in JCR:LA-cp rats. CONCLUSIONS: Both acute (passive) and long-term administration (idiotypic cascade) of chP3R99 antibody reduced low-density lipoprotein and remnant lipoprotein interaction with proteoglycans in an insulin-resistant setting. These findings support the innovative approach of targeting proatherogenic lipoprotein retention by chP3R99 as a passive therapy or as an idiotypic vaccine for atherosclerosis.

Very small size proteoliposomes abrogate cross-presentation of tumor antigens by myeloid-derived suppressor cells and induce their differentiation to dendritic cells.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are among the major obstacles that adjuvants for cancer vaccines have to overcome. These cells cross-present tumor-associated antigens (TAA) to naive T lymphocytes with a tolerogenic outcome. Very Small Size Proteoliposomes (VSSP) is used as adjuvant by four therapeutic cancer vaccines currently in Phase I and II clinical trials. We previously found that VSSP reduces the suppressive function of MDSCs, then activating antigen-specific CTL responses in tumor-bearing (TB) mice, with the consequent reduction of tumor growth. However the mechanistic explanation for the immunomodulatory effect of this adjuvant in TB hosts has not been addressed before. METHODS: TB mice were inoculated with VSSP and MDSCs isolated and characterized by their expression of Arg1 and Nos2 genes by RT-PCR. The effect of VSSP on antigen cross-presentation by MDSCs, regulatory T cells (Tregs) expansion and MDSCs differentiation towards dendritic cells (DCs) was analyzed by FACS. Student's t test or ANOVA and Tukey's tests were used for statistical analyses. RESULTS: After inoculating VSSP into TB mice, a significant reduction of Arg1 and Nos2 gene expression was observed in recovered MDSCs. Concurrently the ability of these cells to induce down-regulation of CD3ζ chain on T cells was lost. Likewise in mice inoculated with the adjuvant lower percentages of Tregs were detected. In vitro, VSSP treatment was enough to differentiate MDSCs into phenotypically mature DCs, eliminating the former suppressive effect. Noteworthy, in vivo administration of VSSP to OVA-expressing (EG.7) TB mice abrogated this model antigen cross-presentation by splenic MDSCs. Similar results were obtained even when OVA antigen was administered into these TB mice formulated in VSSP. On the contrary, immunization with the same protein in polyI:C did not change the percentage of MDSCs expressing SIINFEKL/H-2K(b) complexes, whereas a concomitant injection of VSSP aborted the limitations of polyI:C in this setting. CONCLUSIONS: Altogether, these results indicate that VSSP has the peculiar capacity of inhibiting TAA cross-presentation and certain suppressive mechanisms on MDSCs which in turn, combined with the ability to induce differentiation of these cells into antigen-presenting cells (APCs), sustains this adjuvant as an ideal immunomodulator for cancer immunotherapy.

Intervención educativa sobre anticoncepción y adolescencia / Educational intervention on contraception and adolescence

La adolescencia comprende casi la mitad del período de crecimiento. En el plano biológico, desde el punto de vista de desarrollo del organismo, se considera como edad del adolescente el período enmarcado desde el inicio de la madurez sexual hasta la culminación del mismo. Durante este período surgen y concluyen una serie de modificaciones bioquímicas, anátomo-fisiológicas, psicológicas y corporales que diferencian esencialmente al adolescente del niño y del adulto.Objetivo: elevar el nivel de conocimientos sobre los métodos anticonceptivos en un grupo de adolescentes a través de una intervención educativa.Métodos: se realizó un estudio de intervención educativa en el local 1 del Policlínico Joaquín Agüero y Agüero, en el municipio de Camagüey desde septiembre de 2007 a septiembre de 2008. Resultados: predominó el grupo de adolescentes de 12 a 14 años. La escolaridad la primaria terminada representando cada uno un 48,8 por ciento. El sexo femenino fue más frecuente con un 60 por ciento. La vía por la que ás han escuchado hablar del tema fue por sus profesores. Conclusiones: Con la intervención se elevó el nivel de conocimiento sobre los métodos anticonceptivos en los adolescentes seleccionados

Adolescence comprises almost half of the period of growth. At the biological level, from the point of view of the organism development, it is considered as the adolescent age the period from the beginning of sexual maturity until the culmination itself. During this period emerge and conclude a series of biochemical, anatomicophysiological, psychological and corporeal modifications.Objective: to increase the knowledge level on contraceptive methods in a group of teenagers through an educational intervention.Methods: an educational intervention study was conducted in the local 1 at the Polyclinic Joaquin Agüero y Agüero, in Camagüey municipality from September 2007 to September 2008.Results: the age group from 12 to 14 years prevailed. The female sex was the most frequent with a 60 percent. Through their teachers was the way most have heard talk about. Conclusions: the knowledge level about contraceptive methods in selected adolescents increased

Características biopsicososciales de los ancianos / Biopsychosocial characteristic of the elders

Se realizó un estudio descriptivo de las características psicológicas, biológicas y sociales de los adultos mayores de dos consultorios del policlínico «Joaquín de Agüero y Agüero¼ desde enero de 2006 hasta diciembre del mismo año. Se aplicó el test de Hasegawa para determinar el estado mental de 166 adultos mayores, de los cuales resultaron aptos 154. Se encontró un predominio del sexo femenino y los grupos de edades de 60 a 69 y de 70 a 79 años para un 41.5 %, fueron los más frecuentes. Se señaló que la osteoartrosis es la enfermedad de mayor prevalencia. Se observó que la mayoría se sentían satisfechos con su vida, aunque un número importante se encontraba deprimido; se apreció que ocupaban una función activa en la familia y con relaciones interpersonales e intergeneracionales adecuadas.

A descriptive study of social, biological, and psychological characteristics of the older adults from two doctor's offices at «Joaquín de Agüero y Agüero¼ polyclinic was carried out, from January 2006 to December of the same year. Hasegawa´s test was applied to determine the mental state of 166 older adults, of which 154 turned out to be apt. There was a predominance of female sex and the age groups from 60 to 69 and from 70 to 79 years-old were the most frequent, for a 41.5%. Osteoarthrosis the most prevalent disease it was noted. The majority felt satisfied with their lives it was observed, while a significant number were depressed; it was appreciated that occupied an active function in the family and with interpersonal and intergenerational adequate relations.

Asma bronquial:ssu caracterización en un consultorio / Bronchial asthma: its characterization in a doctor's office

Se realizó un estudio descriptivo para caracterizar la población asmática del consultorio # 40 del médico de familia del Policlínico Docente Joaquín de Agüero de Camagüey, desde enero a diciembre de 2005. El universo estuvo constituido por 38 pacientes dispensarizados como asmáticos a los que se les aplicó una encuesta que contempló las variables grupos de edades, antecedentes familiares, factores desencadenantes y nivel de conocimientos de la enfermedad, la cual constituyó el registro primario de la investigación. Los datos se procesaron según el programa estadístico MICROSTAT, se determinaron estadísticas descriptivas, el mayor por ciento de asmáticos se encontró entre los 15 y 29 años, el polvo fue el mayor factor desencadenante. Se concluyó que sólo un mínimo reducido utilizó el tratamiento no farmacológico en las ínter crisis.

A descriptive study to characterize the asthmatic population of the doctor's office # 40 that belongs at "Joaquín de Agüero" Educational Hospital of Camagüey, from January to December 2005. The universe was constituted by 38 patients considered as asthmatic to which a survey was applied, that contemplated the variables: age groups, family antecedents, triggering factors and knowledge level of the illness, which constituted the primary register of the investigation. Data were processed according to MICROSTAT statistical program, descriptive statistics were determined, the major percent of asthmatic patients was found between 15 and 29 years, the dust was the major triggering factor. It was concluded that only a minimum reduced utilized not pharmacological treatment in the inter crisis.

A sexualidad enllos adolescentes: algunas consideraciones / Sexuality in adolescents: some considerations

Se realizó un estudio descriptivo para conocer el nivel cognoscitivo de los adolescentes sobre sexualidad en el policlínico "Joaquín de Agüero y Agüero" desde diciembre de 2004 a diciembre de 2005. El universo estuvo constituido por 98 adolescentes entre 12 y 19 años de los consultorios del médico de la familia 40 y 46 pertenecientes a este policlínico, de ellos fueron escogidos al azar 42 y se les aplicó una encuesta con las siguientes variables: edad de comienzo de las relaciones sexuales, vías de conocimientos de orientación sexual y de transmisión de ITS. Los datos obtenidos fueron procesados de forma automatizada, se empleó estadística descriptiva. La edad predominante en ambos sexos fue de 13-15 años (64.2 %), el 42.8 % realizó las primeras relaciones sexuales entre los 13 y14 años, fundamentalmente los varones (59 %). La mayoría de los adolescentes tuvo relaciones sexuales y reconoció la vía de transmisión de las infecciones de transmisión sexual.

A descriptive study was carried out in order to describe the cognitive level of the adolescents on sexuality at "Joaquín de Agüero y Agüero" polyclinic from December 2004 to December 2005. The universe was constituted by 98 adolescents between 12 and 19 years from the doctor's offices 40 and 46, belonging to this polyclinic, of them they were chosen at random 42 and applied them itself a survey with the following variables: age of beginning of the sexual intercourses, knowledge ways of sexual orientation, and ITS transmission. The obtained data were processed of automated form, descriptive statistics was employed. The found results were: the predominant age in both sexes was about 13-15 years (64.2%), the 42.8% carried out the first sexual intercourses among the 13 and 14 years, males (59%) fundamentally. The majority of the adolescents had sexual intercourses and they recognized the way of transmission of the sexual infections.