α-Gal Nanoparticles in CNS Trauma: I. In Vitro Activation of Microglia Towards a Pro-Healing State.

BACKGROUND: Macrophages and microglia play critical roles after spinal cord injury (SCI), with the pro-healing, anti-inflammatory (M2) subtype being implicated in tissue repair. We hypothesize that promoting this phenotype within the post-injured cord microenvironment may provide beneficial effects for mitigating tissue damage. As a proof of concept, we propose the use of nanoparticles incorporating the carbohydrate antigen, galactose-α-1,3-galactose (α-gal epitope) as an immunomodulator to transition human microglia (HMC3) cells toward a pro-healing state. METHODS: Quiescent HMC3 cells were acutely exposed to α-gal nanoparticles in the presence of human serum and subsequently characterized for changes in cell shape, expression of anti or pro-inflammatory markers, and secretion of phenotype-specific cytokines. RESULTS: HMC3 cells treated with serum activated α-gal nanoparticles exhibited rapid enlargement and shape change in addition to expressing CD68. Moreover, these activated cells showed increased expression of anti-inflammatory markers like Arginase-1 and CD206 without increasing production of pro-inflammatory cytokines TNF-α or IL-6. CONCLUSION: This study is the first to show that resting human microglia exposed to a complex of α-gal nanoparticles and anti-Gal (from human serum) can be activated and polarized toward a putative M2 state. The data suggests that α-gal nanoparticles may have therapeutic relevance to the CNS microenvironment, in both recruiting and polarizing macrophages/microglia at the application site. The immunomodulatory activity of these α-gal nanoparticles post-SCI is further described in the companion work (Part II).

α-Gal Nanoparticles in CNS Trauma: II. Immunomodulation Following Spinal Cord Injury (SCI) Improves Functional Outcomes.

BACKGROUND: Previous investigations have shown that local application of nanoparticles presenting the carbohydrate moiety galactose-α-1,3-galactose (α-gal epitopes) enhance wound healing by activating the complement system and recruiting pro-healing macrophages to the injury site. Our companion in vitro paper suggest α-gal epitopes can similarly recruit and polarize human microglia toward a pro-healing phenotype. In this continuation study, we investigate the in vivo implications of α-gal nanoparticle administration directly to the injured spinal cord. METHODS: α-Gal knock-out (KO) mice subjected to spinal cord crush were injected either with saline (control) or with α-gal nanoparticles immediately following injury. Animals were assessed longitudinally with neurobehavioral and histological endpoints. RESULTS: Mice injected with α-gal nanoparticles showed increased recruitment of anti-inflammatory macrophages to the injection site in conjunction with increased production of anti-inflammatory markers and a reduction in apoptosis. Further, the treated group showed increased axonal infiltration into the lesion, a reduction in reactive astrocyte populations and increased angiogenesis. These results translated into improved sensorimotor metrics versus the control group. CONCLUSIONS: Application of α-gal nanoparticles after spinal cord injury (SCI) induces a pro-healing inflammatory response resulting in neuroprotection, improved axonal ingrowth into the lesion and enhanced sensorimotor recovery. The data shows α-gal nanoparticles may be a promising avenue for further study in CNS trauma.

Ascariasis infantil: estudio de anticuerpos inmunes antigalactosa mediante glóbulos rojos desializados / Ascariasis in children: a study of anti-galactose antibodies using desialylated red blood cells

La presencia de anticuerpos inmunes del sistema ABO ha sido asociada con enfermedad hemolítica. Los anticuerpos inmunes desaparecen cuando disminuye el estímulo antigénico, por lo que su determinación cuantitativa permitiría la evaluación del curso clínico y la eficacia del tratamiento. El objetivo de este trabajo es estudiar la presencia de anticuerpos inmunes antigalactosa en sueros de niños con ascariasis. Se trabajó con 15 sueros de niños con infección por Ascaris lumbricoides. Se estudiaron los anticuerpos anti-B en el suero: actividad en medio enzimático y en medio salino; inhibición con agarosa; capacidad hemolítica y tratamiento con 2-mercaptoetanol para determinar la clase de inmunoglobulina (lg). Los anticuerpos anti-B mostraron mayor actividad en medio enzimático, presentaron capacidad hemolítica y la mitad de ellos fueron de clase IgG. Se evidenció la presencia de residuos de galactosil por inhibición con agarosa. Se demuestra la presencia de anticuerpos inmunes antigalactosa en niños con ascariasis

The presence of antibodies of the ABO system has been associated with hemolytic disease. The immune antibodies disappear when the antigenic stimulation decreases. Thus, their quantitative determination would allow the evaluation of the clinical course and treatment efficacy. The objective was to study the presence of anti-galactose antibodies in sera of children with ascariasis. Anti-B antibodies were studied in the sera of 15 chil" dren infected with Ascaris lumbricoides to assess their activity in saline and an enzymatic medium, inhibition by agarose, hemolytic capacity and treatment with 2-mercaptoethanol to determine the Ig class. Anti-B antibodies showed more activity in the enzymatic medium and presented hemolytic capacity; half of them were of the IgG class. Agarose inhibition revealed the presence of galactosyl residues. The presence of anti-galactose antibodies was demonstrated in children with ascariasis

A erva-doce e seu efeito galactógeno (um estudo experimental) / The anise and its effects on lactation (an experimental study)

O objetivo do presente trabalho é a comprovaçäo da potencialidade da Erva-doce como estimulante galactógeno. Aplicou-se questionário a gestantes do último trimestre gestacional, inscritas no pré-natal da maternidade do município de Aquiraz, no sentido de selecionar uma amostra intencional, com história comum de desmame precoce por insuficiência de leite. Com base nos resultados obtidos no referido trabalho, pretende-se recomendar a utilizaçäo da Erva-doce, como tecnologia apropriada, o que seria mais uma estrategia para a melhoria da saúde da díade mäe-filho