Ozone oxidative postconditioning ameliorates joint damage and decreases pro-inflammatory cytokine levels and oxidative stress in PG/PS-induced arthritis in rats.

Rheumatoid Arthritis (RA) is the most prevalent chronic condition present in ~1% of the adult population. Many pro-inflammatory mediators are increased in RA, including Reactive Oxygen Species such as nitric oxide NO, pro-inflammatory cytokines as tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß) and other molecules. Ozone oxidative postconditioning has regulatory effects on some pathological targets associated with RA. Thus, the aim of this study was to investigate the efficacy of ozone therapy in PG/PS-induced arthritis in rats in point of joints inflammation and morphology. Moreover, cytokines, nitric oxide and oxidative stress levels in spleen homogenates were evaluated. Ozone treatment ameliorated joint damage, reduced TNF-α concentrations as well as TNF-α and IL-1ß mRNA levels. Besides, cellular redox balance, nitric oxide and fructolysine levels were reestablished after ozone oxidative postconditioning. It was concluded that pleiotropic ozone's effects clarify its therapeutic efficacy in RA. Decreasing inflammation and joint injury, reduction of pro-inflammatory cytokines, TNF-α and IL-1ß transcripts and re-establishment of cellular redox balance after ozone treatment were demonstrated.

Alternativas inmunoterapéuticas para el tratamiento de la aterosclerosis / Immunotherapeotical alternatives for the atherosclerosis treatment

La aterosclerosis representa la primera causa de muerte en el mundo occidental. Aunque existen varias hipótesis que explican su patogénesis, una de las de mayor reconocimiento es la hipótesis autoinmune. La activación del sistema inmunológico frente a diferentes estímulos aterogénicos provoca en el organismo una reacción que puede dañar el endotelio vascular y con ello inducir el desarrollo de una lesión aterogénica. El diseño de nuevas estrategias terapéuticas, entre ellas las vacunas, representan una herramienta con resultados promisorios en el tratamiento de la aterosclerosis. Teniendo en cuenta estos antecedentes, en el presente trabajo se examinó el estado del arte en el campo de la inmunomodulación de esta enfermedad crónica(AU)

Atherosclerosis represents the first cause of death in the western world. Although there are several hypothesis which explain its pathogenesis, one of the most recognized is the autoimmune hypothesis. The activation of the immunological system against different atherogenic stimulus induces a reaction which may affect the vascular endothelium with the consequent atherogenic lesion development. The design of new therapeutic strategies, among them vaccines, represents a tool with promissory result in atherosclerosis treatment. Taking into account these antecedents, in the present work it was examined the state of the art on the immunomodulation of this chronic disease(AU)

Antiatherosclerotic effect of an antibody that binds to extracellular matrix glycosaminoglycans.

OBJECTIVE: Subendothelial retention of proatherogenic lipoproteins by proteoglycans is critical in atherosclerosis. The aim of this study was to characterize the recognition and antiatherogenic properties of a chimeric monoclonal antibody (mAb) that reacts with sulfated molecules. METHODS AND RESULTS: chP3R99 mAb recognized sulfated glycosaminoglycans, mainly chondroitin sulfate (CS), by ELISA. This mAb blocked ≈70% of low-density lipoprotein (LDL)-CS association and ≈80% of LDL oxidation in vitro, and when intravenously injected to Sprague-Dawley rats (n=6, 1 mg/animal), it inhibited LDL (4 mg/kg intraperitoneally, 1 hour later) retention and oxidation in the artery wall. Moreover, subcutaneous immunization of New Zealand White rabbits (n=19) with chP3R99 mAb (100 µg, 3 doses at weekly intervals) prevented Lipofundin-induced atherosclerosis (2 mL/kg, 8 days) with a 22-fold reduction in the intima-media ratio (P<0.01). Histopathologic and ultrastructural studies showed no intimal alterations or slight thickening, with preserved junctions between endothelial cells and scarce collagen fibers and glycosaminoglycans. In addition, immunization with chP3R99 mAb suppressed macrophage infiltration in aorta and preserved redox status. The atheroprotective effect was associated with the induction of anti-CS antibodies in chP3R99-immunized rabbits, capable of blocking CS-LDL binding and LDL oxidation. CONCLUSION: These results support the use of anti-sulfated glycosaminoglycan antibody-based immunotherapy as a potential tool to prevent atherosclerosis.

Comparación entre dos biomodelos murinos en el ensayo de la morfología de la cabeza del espermatozoide / Two murine biomodels comparison in the head sperm morphology assay

Este trabajo tuvo como objetivo realizar una comparación entre el ratón Balb/c y ratas Sprague Dawley (SD) como biomodelo en el ensayo de la morfología de la cabeza del espermatozoide, teniendo en cuenta la frecuencia de formas anómalas en la cabeza del espermatozoide basales e inducidas con ciclofosfamida (CF). Se utilizaron 20 animales/grupo de la línea de ratón Balb/c y de ratas Sprague Dawley, administrados durante 35 días en el ratón y 52 días en la rata. Se creó un grupo control negativo (no administrado), dos controles con sustancias vehículo y un control positivo administrado con CF 50 mg/kg por vía intraperitoneal durante cinco días consecutivos. El mejor biomodelo experimental resultó ser el de los ratones Balb/c que difirió significativamente con los resultados obtenidos en las ratas SD, teniendo en cuenta los valores espontáneos e inducidos en la concentración espermática y la frecuencia de espermatozoides morfológicamente anómalos en epidídimos. Este estudio permitirá utilizar esta línea de ratón con mayor eficiencia en la evaluación genotóxica y toxicológica de la fertilidad preclínica de drogas, vacunas y otros productos(AU)

This research aimed at comparing Balb/c mice and Sprague Dawley rats as biomodel in the head sperm morphology assay, keeping in mind the frequency in anomalous forms in the sperm head basal and induced with cyclophosphamide (CF). Twenty animals/group were used of Balb/c mice line and Sprague Dawley (SD) rats, administered during 35 days in the mouse and 52 days in the rat. Using a negative control group (not administered), two substance-vehicle controls and positive control CF administered with 50 mg/kg, by intraperitoneal route during five consecutives days. The best experimental biomodel turns out to be the Balb/c mice differing significantly from the results obtained in the SD rats, keeping in mind the spontaneous and induced values in the spermatic concentration and the frequency of anomalous epididymis sperms. This study will allow to use mice species with more efficiency in the genotoxic and preclinical toxicology fertility evaluation of drugs, vaccine and other products(AU)

Biomodelos para la inducción de micronúcleos en células de la médula ósea por ciclofosfamida y bleomicina / Biomodels for micronucleis induction on bone marrow cells by cyclophosphamide and bleomycin

En este trabajo se evaluó la línea de ratones Balb/c, de ambos sexos, como biomodelo en la inducción de micronúcleos en células de la médula ósea por ciclofosfamida y bleomicina. Se formaron cinco grupos experimentales/sexo: al primero se le administró NaCl al 0,9 po ciento , al segundo y al tercero ciclofosfamida y al cuarto y quinto bleomicina. Todos los medicamentos fueron suministrados por vía intraperitoneal, con diseños de tratamientos diferentes y dosis de 50 mg/kg en los tres primeros grupos y de 20 mg/kg en los dos últimos. Se obtuvo como resultado una mayor inducción de micronúcleos en eritrocitos policromáticos y un mayor índice de citotoxicidad por el uso de la ciclofosfamida, administrada en dos ocasiones antes del sacrificio, con intervalos de 24 horas entre ambas administraciones. Esto constituyó, bajo nuestras condiciones experimentales, el mejor diseño para inducir un número considerable de micronúcleos en células de la médula ósea de ratones, siendo estos resultados útiles para evaluar drogas con efecto antigenotóxico y pudiera servir también como control positivo en estudios de mutagénesis o genotoxicidad(AU)

Balb/c mice of both sexes were evaluated as biomodel in the induction of micronucleis in bone marrow cells by cyclophosphamide and bleomycin. They were divided into five experimental groups per sex. The first one was administered with NaCl 0,9 por ciento by intraperitoneal (i.p) route, the second and third groups were administered with cyclophosphamide by i.p route, with designs of different treatments at doses of 50 mg/kg. The fourth and fifth groups were administered with bleomycin by i.p route, equally in two designs of different treatments at 20 mg/kg doses. This resulted in a higher micronucleis induction of polychromatic erythrocytes and in a higher citotoxicity index with the use of cyclophosphamide administered twice before the sacrifice, with a 24-hours interval between administrations. According to our experimental conditions, this is the best design to induce a considerable number of micronucleis in bone marrow cells of mice, being useful in experimental designs to evaluate drugs with antigenotoxic effect. In addition, it implies its use according to the best found experimental design as positive control in mutagenesis and genotoxicity studies(AU)