Treatment with Nasal Neuro-EPO Improves the Neurological, Cognitive, and Histological State in a Gerbil Model of Focal Ischemia

Vascular illness of the brain constitutes the third cause of death and the first cause of disability in Cuba and many other countries. Presently, no medication has been registered as a neuroprotector. Neuroprotection with intranasal Neuro-EPO (EPO, erythropoietin) has emerged as a multifunctional therapy that plays a significant role in neural survival and functional recovery in an animal model of stroke. On the other hand, there is limited access to the brain through the blood brain barrier (BBB) for intravenously applied EPO, and the high EPO dosages needed to obtain a protective effect increase the danger of elevated hematocrit levels and practically exclude chronic or subchronic treatment with EPO. A promising approach has been recently developed with a nonerythropoietic variant of EPO, Neuro-EPO, with low sialic acid content, a very short plasma half-life, and without erythropoietic activity, probably similar to endogenous brain EPO. The objective of this work was to determine the neuroprotective effect of intranasal Neuro-EPO in comparison with the human recombinant EPO injected intraperitoneally in the acute phase of cerebral ischemia, employing the common carotid artery occlusion model in gerbils. Neuro-EPO has demonstrated a better neuroprotective effect, evidenced through increased viability, improvements of the neurological state and cognitive functions, as well as protection of the CA3 region of the hippocampus, temporal cortex, and the thalamus. In conclusion, the intranasal application of Neuro-EPO has a better neuroprotective effect than intraperitoneal EPO, evidenced by the significant improvement of neurological, cognitive, and histological status in the animal model of stroke employed

Efficacy of supraspinatus tendon repair using mesenchymal stem cells along with a collagen I scaffold

Objectives: Our main objective was to biologically improve rotator cuff healing in an elderly rat model using mesenchymal stem cells (MSCs) in combination with a collagen membrane and compared against other current techniques. Methods: A chronic rotator cuff tear injury model was developed by unilaterally detaching the supraspinatus (SP) tendons of Sprague-Dawley rats. At 1 month postinjury, the tears were repaired using one of the following techniques: (a) classical surgery using sutures (n = 12), (b) type I collagen membranes (n = 15), and (c) type I collagen membranes + 1 × 106 allogeneic MSCs (n = 14). Lesion restoration was evaluated at 1, 2, and 3 months postinjury based on biomechanical criteria. Continuous variables were described using mean and standard deviation (SD). To analyse the effect of the different surgical treatments in the repaired tendons’ biomechanical capabilities (máximum load, stiffness, and deformity), a two-way ANOVA model was used, introducing an interaction between such factor and time (1, 2, and 3 months postinjury). Results: With regard to maximum load, we observed an almost significant interaction between treatment and time (F = 2.62, df = 4, p = 0.053). When we analysed how this biomechanical capability changed with time for each treatment, we observed that repair with OrthADAPT and MSCs was associated with a significant increase in maximum load (p = 0.04) between months 1 and 3. On the other hand, when we compared the different treatments among themselves at different time points, we observed that the repair with OrthADAPT and MSCs has associated with a significant higher maximum load, when compared with the use of suture, but only at 3 months (p = 0.014). With regard to stiffness and deformity, no significant interaction was observed (F = 1.68, df = 4, p = 0.18; F = 0.40, df = 4, p = 0.81; respectively). Conclusions: The implantation of MSCs along with a collagen I scaffold into surgically created tendon defects is safe and effective. MSCs improved the tendon’s maximum load over time, indicating that MSCs could help facilitate the dynamic process of tendon repair

An Intranasal Formulation of Erythropoietin (Neuro-EPO) Prevents Memory Deficits and Amyloid Toxicity in the APPSwe Transgenic Mouse Model of Alzheimer’s Disease

International audienc

Calidad de vida y trabajo: algunas consideraciones útiles para el profesional de la información

A group of basic theoretical elements related to health and the quality of life of white-collar workers is studied. Concepts as health, quality of life, and healthy housing are defined. The health of the worker is analyzed in three dimensions: family, the working setting and environment. Subjective factors which influence on the quality of life of the workers are also dealt with. To improve the workers' quality of life, starting from the modifications of their negative out-of-work behaviors and from the contribution to a process of personal growth and consolidation of family values, is the means to achieve a strategic alliance among family, organization, and environment. From this perspective it is possible to aspire to an equitable health -health for all-, to add life to years -to improve the quality of life, to add years to life-to reduce the mortality rate, and to add health to life - to reduce the occupational diseases

Dose Effect Evaluation and Therapeutic Window of the Neuro-EPO Nasal Application for the Treatment of the Focal Ischemia Model in the Mongolian Gerbil

Cerebrovascular disease is the third leading cause of death and the leading cause of disability in Cuba and in several developed countries. A possible neuroprotective agent is the rHu-EPO, whose effects have been demonstrated in models of brain ischemia. The Neuro-EPO is a derivative of the rHu-EPO that avoids the stimulation of erythropoiesis. The aim of this study was to determine the Neuro-EPO delivery into the central nervous system (CNS) to exert a neuroprotective effect in cerebral ischemia model of the Mongolian gerbil. The Neuro-EPO in a rate of 249.4 UI every 8 hours for 4 days showed 25% higher viability efficacy (>0.01), improving neurological score and behavior of the spontaneous exploratory activity, the preservation of CA3 areas of the hippocampus, the cortex, and thalamic nuclei in the focal ischemia model of the Mongolian gerbil. In summary, this study, the average dose-used Neuro-EPO (249.4 UI/10 μL/every 8 hours for 4 days), proved to be valid indicators of viability, neurological status, and spontaneous exploratory activity, being significantly lower than that reported for the systemically use of the rHu-EPO as a neuroprotectant. Indeed, up to 12 h after brain ischemia is very positive Neuro-EPO administration by the nasal route as a candidate for neuroprotection

Intranasal formulation of erythropoietin (EPO) showed potent protective activity against amyloid toxicity in the Aβ 25-35 non-transgenic mouse model of Alzheimer’s disease

International audienceErythropoietin (EPO) promotes neurogenesis and neuroprotection. We here compared the protection induced by two EPO formulations in a rodent model of Alzheimer's disease (AD): rHu-EPO and a low sialic form, Neuro-EPO. We used the intracerebroventricular administration of aggregated Aβ₂₅₋₃₅ peptide, a non-transgenic AD model. rHu-EPO was tested at 125-500 µg/kg intraperitoneally and Neuro-EPO at 62-250 µg/kg intranasally (IN). Behavioural procedures included spontaneous alternation, passive avoidance, water-maze and object recognition, to address spatial and non-spatial, short- and long-term memories. Biochemical markers of Aβ₂₅₋₃₅ toxicity in the mouse hippocampus were examined and cell loss in the CA1 layer was determined. rHu-EPO and Neuro-EPO led to a significant prevention of Aβ₂₅₋₃₅-induced learning deficits. Both EPO formulations prevented the induction of lipid peroxidation in the hippocampus, showing an antioxidant activity. rHu-EPO (250 µg/kg) or Neuro-EPO (125 µg/kg) prevented the Aβ₂₅₋₃₅-induced increase in Bax level, TNFα and IL-1β production and decrease in Akt activation. A significant prevention of the Aβ₂₅₋₃₅-induced cell loss in CA1 was also observed. EPO is neuroprotective in the Aβ₂₅₋₃₅ AD model, confirming its potential as an endogenous neuroprotection system that could be boosted for therapeutic efficacy. We here identified a new IN formulation of EPO showing high neuroprotective activity. Considering its efficacy, ease and safety, IN Neuro-EPO is a new promising therapeutic agent in AD

Different Expression Patterns of Ngb and EPOR in the Cerebral Cortex and Hippocampus Revealed Distinctive Therapeutic Effects of Intranasal Delivery of Neuro-EPO for Ischemic Insults to the Gerbil Brain

The purpose of this study was to evaluate the neuroprotective effects of intranasally delivered recombinant human neuronal erythropoietin (Neuro-EPO) on brain injury induced by unilateral permanent ischemia in the Mongolian gerbil. Expression of EPO receptor (EPOR) and neuroglobin (Ngb) over 5 weeks after intranasal treatment with Neuro-EPO was determined using immunohistochemistry. Mortality of Neuro-EPO-treated gerbils decreased after surgery, and the sensory and motor function was significantly improved. Histopathological mapping showed that Neuro-EPO significantly reduced delayed neuronal death in the brain. Expression of Ngb was upregulated in the cerebral cortex at most time points (expect for 10 min and 48 hr) and in the hippocampus at 10 min and from 48 hr to 5 weeks, whereas EPOR was almost downregulated or unchanged in the brain (expect for 48 hr). The 10 min and 48 hr seemed to be two time points for the brain to switch the expression of both Ngb and EPOR to early and late recovery phase, respectively. In addition, there were two phases, 10 min to 1 hr and 24 hr to 72 hr, respectively, closing to the “golden hour” of about 60 min and the “silver day” of 1 to 3 days, for the brain to recover from stroke onset with intranasal Neuro-EPO treatment. Therefore, the results suggest that the intranasal administration of Neuro-EPO is effective in the treatment of acute brain ischemia. The different expression patterns of Ngb and EPOR is probably due to ischemic tolerance in the cerebral cortex and ischemic sensitivity in the hippocampus

Monoclonal antibody generated against Nile tilapia (Oreochromis niloticus) IgT heavy chain using a peptide-based strategy

Teleost IgT/Z plays a principal role in the defense mechanisms against infectious agents in the mucosal compartments and in systemic immunity. Previously, Nile tilapia (Oreochromis niloticus) IgT was discovered and characterized at transcription level. In this work, we generated a monoclonal antibody (mAb) that specifically recognized the Nile tilapia IgT. BALB/c mice were immunized with three synthetic peptides conjugated to KLH. The sequences of these peptides derived from the constant region of the Nile tilapia IgT heavy chain. ELISA and Western blotting confirmed the specificity of the polyclonal sera and the culture supernatant from a positive hybridoma clone. We observed immunoreactivity against a recombinant IgT fragment and native IgT in skin mucus. The anti-IgT mAb did not cross-react with purified tilapia IgM. Direct ELISA analysis allowed the quantification of skin mucus IgM and IgT concentrations. Flow cytometry analysis revealed differences in the percentage of IgT+ B cell populations between juveniles and adults in peripheral blood, head kidney and spleen lymphocytes and among the tissues analyzed. For further validation of the anti-IgT mAb utility, a recombinant vaccine candidate against sea lice (TT-P0 Ls) was injected into juvenile tilapia. Direct ELISA results revealed a differential secretion of skin mucus IgT and IgM after immunostimulation. In addition, the percentages of IgT+ B cells were determined at 7 days after booster and ex-vivo stimulation by flow cytometry. This mAb constitutes an important immunological tool to study the biological function and structural characteristics of tilapia IgT

Caracterización de los sistemas de captación de agua de los cantones de Hojancha y Nicoya, en Guanacaste, Costa Rica

Capítulo 2 del libro digital: Clima, agua y producción sostenible: Aportes desde la acción académica CEMEDE - HIDROCECEn esta investigación se caracterizaron los sistemas de captación de agua en los cantones de Hojancha y Nicoya, en Guanacaste, Costa Rica. Específicamente, se documentaron las razones que incentivaron a los agricultores a construir estos sistemas. Adicionalmente, se analizó la percepción de los agricultores acerca del estado actual del funcionamiento de estos sistemas, así como, de los beneficios obtenidos durante los meses de aridez estacional. La información fue obtenida por medio de visitas a las fincas, registrando la ubicación espacial de los sistemas, tomando fotografías del estado actual de la infraestructura de los sistemas. Además, se utilizaron encuestas que fueron aplicadas en finca, a los once dueños de sistemas de captación de agua. El diseño colaborativo de la metodología, así como el trabajo de campo, la transcripción de las encuestas y el análisis de la información fue realizada por los estudiantes y académicos de la Universidad Nacional (UNA). Los productores encuestados establecieron que el principal beneficio de los sistemas de captación es que pueden proporcionar el agua necesaria para desarrollar actividades agropecuarias durante la aridez estacional (seis meses). Esta es la temporada más difícil para el desarrollo de la ganadería y la agricultura en estos cantones. Los sistemas de captación de agua les permiten adaptarse a los problemas de escasez hídrica que se han agravado en los últimos diez años. A partir del análisis de los resultados, se identificaron oportunidades para mejorar el diseño técnico de los sistemas, así como, la necesidad de continuar investigando, a fin de, evaluar la eficiencia de la tecnología y las implicaciones de implementar los sistemas de captación de agua, para solventar la disponibilidad hídrica en la región.Centro Mesoamericano de Desarrollo Sostenible del Trópico Seco (CEMEDE-UNA)Universidad Nacional, Costa RicaUniversidad Nacional, Sede Regional Chorotega, Costa RicaCentro Mesoamericano de Desarrollo Sostenible del Trópico Seco (CEMEDE-UNA