Nose-to-Brain Delivery of Dexamethasone: Biodistribution Studies in Mice.

Neuroinflammation (NI) is an important physiologic process which promotes the tissue repair and homeostatic maintenance in the central nervous system after different types of insults. However, when it is exacerbated and sustained in time, NI plays a critical role in the pathogenesis of different neurologic diseases. The high systemic doses required for brain-specific targeting lead to severe undesirable effects. The intranasal (IN) route has been proposed as an alternative drug administration route for a better NI control. Herein, the brain biodistribution of intranasally administered dexamethasone versus intravenously administered one is reported. A higher amount of dexamethasone was found in every analyzed region of those brains of intranasally administered mice. HPLC analysis also revealed that IN administration allows Dex to arrive faster and in a greater concentration to the brain in comparison with intravenous administration, data confirmed by immunofluorescence and HPLC analysis. These data support the proposal of the IN administration of Dex as an alternative for a more efficient control of NI. SIGNIFICANCE STATEMENT: This work highlights the biodistribution of dexamethasone after its intranasal administration. Intranasal administration allows for a faster arrival, better distribution, and a higher concentration of the drug within the brain compared to its intravenous administration. These results explain some of the evidence shown in a previous work in which dexamethasone controls neuroinflammation in a murine stroke model and can be used to propose alternative treatments for neuroinflammatory diseases.

Expression of immunogenic poliovirus Sabin type 1 VP proteins in transgenic tobacco.

One of the milestones of vaccinology is the depletion of the global impact of Poliomyelitis. The current vaccines to deal with Polio comprise the Sabin and Salk formulations. The main limitation of the former is the use of attenuated viruses that can revert into pathogenic forms, whereas the latter is more expensive and induces no protection in the intestinal tract; the site of virus replication. Genetically engineered plants cope with such limitations. In addition, they offer a low-cost alternative for production, storage and delivery of vaccines. This technology has been narrowly applied in the development of Polio vaccines. Herein, we explored the ability of tobacco cells to express the immunogenic VP1, VP2, VP3, and VP4 Polio antigens, which are relevant for vaccine development. Evidence on the expression of the plant-made Polio VPs is presented and an immunogenicity assessment proved their capacity to induce local and systemic humoral responses when administered by subcutaneous and oral routes. The plant-made VPs will be useful in the development of low-cost vaccine formulations able to induce effective mucosal immunity without the risks associated to the use of attenuated viruses; therefore there is a potential for this technology to contribute toward Polio eradication.

Alpha-mangostin: Anti-inflammatory and antioxidant effects on established collagen-induced arthritis in DBA/1J mice.

Rheumatoid arthritis (RA) is an autoimmune disease that causes physical disability in people worldwide. Despite progress made in RA treatment in the past decade, new drugs with high efficacy but few long-term adverse effects are still needed. This study focused on evaluating the therapeutic potential of α-mangostin on established collagen-induced arthritis (CIA) in DBA/1J mice. Arthritic DBA/1J mice were orally administered with two doses of α-mangostin (10 and 40 mg/kg) daily, for 33 days. Alpha-mangostin significantly decreased the clinical score in the short term at both doses and decreased the histopathological score at the higher dose. This improvement was accompanied by a reduction on serum levels of anti-collagen IgG2a autoantibodies and of the production of LIX/CXCL5, IP-10/CXCL10, MIG/CXCL9, RANTES/CCL5, IL-6 and IL-33 in the joints of CIA mice. Alpha-mangostin also exhibited an anti-oxidant effect decreasing the NADPH oxidase activity and lipid peroxidation and preserving the levels of reduced glutathione in the arthritic joints. In vitro this xanthone demonstrated modulatory properties on LPS-activated dendritic cells, although in Th1 and Th17-polarized lymphocytes promotes a pro-apoptotic phenotype. Altogether this study illustrates the capacity of α-mangostin to ameliorate the early clinical and histological signs of established CIA by reducing the inflammatory and oxidative responses.

[Evaluation of the impact of a control program against taeniasis-cysticercosis (Taenia solium)]. / Evaluación del impacto de un programa de control de la teniasis-cisticercosis (Taenia solium).

OBJETIVE: The impact of a control program is evaluated to eventually eradicate taeniasis-cysticercosis (Taenia solium) based on education and vaccination of pigs. MATERIALS AND METHODS: The prevalence of porcine cysticercosis was estimated using tongue inspection, ultrasound and determination of antibodies, before and three years after the application in three regions of the state of Guerrero. RESULTS: A significant reduction in the prevalence of porcine cysticercosis of 7 to 0.5% and 3.6 to 0.3% estimated by tongue examination or ultrasound respectively (p<0.01) and a no significant decrease in seroprevalence from 17.7 to 13.3% were observed. CONCLUSIONS: The reduction of the prevalence of taeniasis-cysticercosis establishes the program's effectiveness in preventing infection. The sustained presence of antibodies, compatible with contact of Taenia solium or other related helminths, underlines the importance of maintaining interventions to achieve eradication.

Evaluación del impacto de un programa de control de la teniasis-cisticercosis (Taenia solium) / Evaluation of the impact of a control program against taeniasis-cysticercosis (Taenia solium)

Objetivo. Evaluar el impacto de un programa de control de la teniasis-cisticercosis por Taenia solium con fines de erradicación, basado en educación de la comunidad y vacunación de cerdos. Material y métodos. Se estimó la prevalencia de cisticercosis porcina por medio de la palpación de lengua, ultrasonido y presencia de anticuerpos en suero, antes de iniciar el programa y tres años después, en tres regiones del estado de Guerrero. Resultados. Se observó una reducción significativa en la prevalencia de cisticercosis porcina de 7 a 0.5% y de 3.6 a 0.3%, estimadas por examen de lengua y ultrasonido, respectivamente (p<0.01), y una disminución no significativa de la seroprevalencia de 17.7 a 13.3%. Conclusiones. La reducción de la prevalencia de teniasis-cisticercosis comprueba la efectividad del programa para prevenir la infección. La presencia sostenida de anticuerpos es compatible con continuos contactos con Taenia solium u otros helmintos relacionados, y señala la necesidad de mantener las intervenciones para lograr su erradicación.

Objetive. The impact of a control program is evaluated to eventually eradicate taeniasis-cysticercosis (Taenia solium) based on education and vaccination of pigs. Materials and methods. The prevalence of porcine cysticercosis was estimated using tongue inspection, ultrasound and determination of antibodies, before and three years after the application in three regions of the state of Guerrero. Results. A significant reduction in the prevalence of porcine cysticercosis of 7 to 0.5% and 3.6 to 0.3% estimated by tongue examination or ultrasound respectively (p<0.01) and a no significant decrease in seroprevalence from 17.7 to 13.3% were observed. Conclusions. The reduction of the prevalence of taeniasis-cysticercosis establishes the program's effectiveness in preventing infection. The sustained presence of antibodies, compatible with contact of Taenia solium or other related helminths, underlines the importance of maintaining interventions to achieve eradication.

Identification of loci controlling restriction of parasite growth in experimental Taenia crassiceps cysticercosis.

Human neurocysticercosis (NC) caused by Taenia solium is a parasitic disease of the central nervous system that is endemic in many developing countries. In this study, a genetic approach using the murine intraperitoneal cysticercosis caused by the related cestode Taenia crassiceps was employed to identify host factors that regulate the establishment and proliferation of the parasite. A/J mice are permissive to T. crassiceps infection while C57BL/6J mice (B6) are comparatively restrictive, with a 10-fold difference in numbers of peritoneal cysticerci recovered 30 days after infection. The genetic basis of this inter-strain difference was explored using 34 AcB/BcA recombinant congenic strains derived from A/J and B6 progenitors, that were phenotyped for T. crassiceps replication. In agreement with their genetic background, most AcB strains (A/J-derived) were found to be permissive to infection while most BcA strains (B6-derived) were restrictive with the exception of a few discordant strains, together suggesting a possible simple genetic control. Initial haplotype association mapping using >1200 informative SNPs pointed to linkages on chromosomes 2 (proximal) and 6 as controlling parasite replication in the AcB/BcA panel. Additional linkage analysis by genome scan in informative [AcB55xDBA/2]F1 and F2 mice (derived from the discordant AcB55 strain), confirmed the effect of chromosome 2 on parasite replication, and further delineated a major locus (LOD = 4.76, p<0.01; peak marker D2Mit295, 29.7 Mb) that we designate Tccr1 (T. crassiceps cysticercosis restrictive locus 1). Resistance alleles at Tccr1 are derived from AcB55 and are inherited in a dominant fashion. Scrutiny of the minimal genetic interval reveals overlap of Tccr1 with other host resistance loci mapped to this region, most notably the defective Hc/C5 allele which segregates both in the AcB/BcA set and in the AcB55xDBA/2 cross. These results strongly suggest that the complement component 5 (C5) plays a critical role in early protective inflammatory response to infection with T. crassiceps.

Estructura etaria, comportamiento productivo y reproductivo de una población de cerdos criados en semiconfinamiento, en una comunidad rural del estado de Morelos, México / Age structure, productive and reproductive behavior of a pig population reared in semi-confinement in a rural community of Morelos state, Mexico

Small-scale family swine production can be seen in thousands of small communities and suburban zones; it is characterized by breeding rural pigs in rustic facilities with basic feed and productive parameters, well below those of technologically advanced farms, with mortality reaching up to 50% of the litter. This type of production involves a large number of producers and has a critical impact on family income. At slaughter, these carcasses have a high probability of being seized because of the presence of cysticercoids (T. solium), losing a high percentage of its economic value; due to absence of slaughterhouses in rural communities, this meat is directed to consumption without health inspection, increasing the risk of transmission of this zoonosis. This paper describes the productive and reproductive characteristics of the backyard production system of pigs in a rural community. Human to pig ratio was 3:1. During the year, 308 piglets were born in 43 litters, 51.7% males and 48.3% females, with an average weight of 40.47 kg at 6 months and 65.30 kg at 10 months. They were slaughtered at 7.3 months on average. The highest death rate was found between 0 and 1 month of age. In many rural communities of Mexico pigs are fed with waste generated in homes, helping maintain the communities clean, as well as with the excreta of other species that usually roam freely, situation that can promote dissemination of parasitic diseases.

La porcicultura familiar es una forma de producción que existe en miles de pequeñas comunidades y zonas conurbadas, caracterizada por la crianza de razas criollas en instalaciones rústicas, con alimentación básica y parámetros productivos inferiores a los de las granjas tecnificadas y una mortalidad hasta de 50% de la camada. Este tipo de producción involucra gran número de productores e impacta críticamente en el ingreso familiar. Al sacrificio, estas canales tienen una alta probabilidad de decomiso por la presencia de cisticercosis (T. solium), por lo que pierden un alto porcentaje de su valor económico; debido a la ausencia de rastros en comunidades rurales, esta carne se destina al consumo directo, sin inspección sanitaria, incrementando los riesgos de transmisión de esta zoonosis. En este trabajo se describen las características productivas y reproductivas del sistema de producción de cerdos en traspatio en una comunidad rural. La razón humano-cerdo fue de 3:1, durante el año se obtuvieron 43 camadas, con 308 lechones nacidos vivos, 51.7% machos y 48.3% hembras, con un peso promedio de 40.47 kg a los 6 meses y 65.30 kg a los 10 meses, siendo sacrificados a los 7.3 meses en promedio, los animales que tienen entre 0 y 1 mes de edad presentan la tasa más alta de mortalidad sin que sean sacrificados. En muchas comunidades rurales de México, se alimentan con desperdicios que se generan en las casas, así como las excretas de otras especies que por lo regular deambulan libremente, situación que puede generar enfermedades parasitarias.