Comparison of the protective effects of direct ischemic preconditioning and remote ischemic preconditioning in a rabbit model of transient spinal cord ischemia

Abstract

Introduction

This study aimed to determine the relative potency of direct ischemic preconditioning (DIPC) and remote ischemic preconditioning (RIPC) for protection against ischemic spinal cord injury in rabbits and to explore the mechanisms involved.

Methods

In experiment 1, we compared the neurological and histopathological outcomes of DIPC, kidney RIPC, and limb RIPC. The DIPC and kidney RIPC groups received two cycles of 5-min occlusion/15-min reperfusion of the abdominal aorta and left renal artery, respectively. The limb RIPC group received two cycles of 10-min occlusion/10-min reperfusion of the femoral arteries bilaterally. Thirty minutes after the conditioning ischemia, spinal cord ischemia was produced by occluding the abdominal aorta for 15 min. In experiments 2 and 3, we investigated whether pretreatment using a free-radical scavenger, dimethylthiourea (DMTU), an adenosine A₁ receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or a mitochondrial ATP-sensitive potassium channel antagonist, 5-hydroxydecanoate (5HD), could attenuate the protective effects of DIPC. In experiment 4, comprehensive analysis of phosphorylated proteins in the spinal cord was performed using a Proteome Profiler Array followed by immunoblotting to elucidate the signal pathway activated by DIPC.

Results

In experiment 1, DIPC improved the neurological and histopathological outcomes, whereas kidney and limb RIPC had no protective effects. In experiments 2 and 3, strong protective effects of DIPC were reconfirmed but were not attenuated by DMTU, DPCPX, or 5HD. In experiment 4, DIPC induced phosphorylation of Akt2.

Conclusions

DIPC, but not kidney or limb RIPC, protected against ischemic spinal cord injury in rabbits. Akt2 might contribute to this protective effect.

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The allergen-specificity of early peanut consumption and the impact on the development of allergic disease in the LEAP Study Cohort

Publication date: Available online 31 October 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): George du Toit, Peter H. Sayre, Graham Roberts, Kaitie Lawson, Michelle L. Sever, Henry T. Bahnson, Helen R. Fisher, Mary Feeney, Suzana Radulovic, Monica Basting, Marshall Plaut, Gideon Lack
BackgroundEarly introduction of dietary peanut in high-risk infants with severe eczema and/or egg allergy prevented peanut allergy at 5 years of age in the LEAP Study; the protective effect persisted after 12 months of avoiding peanuts in the LEAP-On Study. It is unclear whether this benefit is allergen and allergic-disease specific.ObjectiveTo assess the impact of early introduction of peanut on the development of allergic disease, food sensitization and aeroallergen sensitization.MethodsAsthma, eczema and rhinoconjunctivitis were diagnosed by clinical assessment. Reported allergic reactions and consumption of tree nuts and sesame were recorded by questionnaire. Sensitization to food and aeroallergens was determined by skin prick testing and specific IgE measurement.ResultsA high and increasing burden of food and aeroallergen sensitization and allergic disease was noted across study time points; 76% of LEAP participants had at least one allergic disease at 60 months of age. There were no differences in allergic disease between LEAP groups. There were small differences in sensitization and reported allergic reactions for select tree nuts; levels were higher in the LEAP consumption group. Significant resolution of eczema and sensitization to egg and milk occurred in LEAP participants; this was not affected by peanut consumption.ConclusionEarly consumption of peanut in infants at high risk of peanut allergy is allergen-specific and does not prevent the development of other allergic disease, sensitization to other foods and aeroallergens, or reported allergic reactions to tree nuts and sesame. Furthermore, peanut consumption does not hasten the resolution of eczema or egg allergy.

Teaser

The early consumption of peanut in high-risk infants is allergen-specific and protects against peanut allergy but does not prevent the development of sensitization to other allergens or allergic diseases.


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Carcinoma mucoepidermoide de bajo grado de glándula salival menor de lengua en un paciente pediátrico

Publication date: Available online 31 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): María Fernanda Vargas Gamarra, José María Perolada Vilmaña, Miguel Armengot Carceller




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BRAF peptide vaccine facilitates therapy of murine BRAF-mutant melanoma

Abstract

Approximately, 50% of human melanomas are driven by BRAF mutations, which produce tumors that are highly immunosuppressive and often resistant to vaccine therapy. We introduced lipid-coated calcium phosphate nanoparticles (LCP NPs) as a carrier to efficiently deliver a tumor-specific antigen, the BRAF^V600E peptide, to drive dendritic cell (DC) maturation and antigen presentation in C57BL6 mice. The BRAF peptide vaccine elicited a robust, antigen-specific cytotoxic T cell response and potent tumor growth inhibition in a murine BRAF-mutant melanoma model. Advanced BRAF-specific immune response was illustrated by IFN-γ production assay and cytotoxic T lymphocyte (CTL) assay. Remodeling of immunosuppressive modules within the tumor microenvironment further facilitated CTL infiltration. Thus, using LCP NPs to deliver the BRAF peptide vaccine is a promising strategy for the BRAF-mutant melanoma therapy.

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A phase I vaccination study with dendritic cells loaded with NY-ESO-1 and α-galactosylceramide: induction of polyfunctional T cells in high-risk melanoma patients

Abstract

Vaccines that elicit targeted tumor antigen-specific T-cell responses have the potential to be used as adjuvant therapy in patients with high risk of relapse. However, the responses induced by vaccines in cancer patients have generally been disappointing. To improve vaccine function, we investigated the possibility of exploiting the immunostimulatory capacity of type 1 Natural killer T (NKT) cells, a cell type enriched in lymphoid tissues that can trigger improved antigen-presenting function in dendritic cells (DCs). In this phase I dose escalation study, we treated eight patients with high-risk surgically resected stage II–IV melanoma with intravenous autologous monocyte-derived DCs loaded with the NKT cell agonist α-GalCer and peptides derived from the cancer testis antigen NY-ESO-1. Two synthetic long peptides spanning defined immunogenic regions of the NY-ESO-1 sequence were used. This therapy proved to be safe and immunologically effective, inducing increases in circulating NY-ESO-1-specific T cells that could be detected directly ex vivo in seven out of eight patients. These responses were achieved using as few as 5 × 10⁵ peptide-loaded cells per dose. Analysis after in vitro restimulation showed increases in polyfunctional CD4⁺ and CD8⁺ T cells that were capable of manufacturing two or more cytokines simultaneously. Evidence of NKT cell proliferation and/or NKT cell-associated cytokine secretion was seen in most patients. In light of these strong responses, the concept of including NKT cell agonists in vaccine design requires further investigation.

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Comparing ultrasound-guided and fiberscope-guided intubation

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The Puck Stops Here: Evolving Social Norms of Helmet Usage in the National Hockey League

Wise, SC; Scott, S; (2012) The Puck Stops Here: Evolving Social Norms of Helmet Usage in the National Hockey League. In: (Proceedings) CSSSA 2012: The Computational Social Science Society of the Americas 2012 Conference, 18-21 September 2012, Santa Fe, New Mexico, USA.

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