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BACKGROUND: Peripheral neuropathy (PN) constitutes a dose-limiting side effect of oxaliplatin chemotherapy that often compromises the efficacy of antineoplastic treatments. Sensory neurons damage in dorsal root ganglia (DRG) are the cellular substrate of PN complex molecular origin. Dehydropeptidase-1 (DPEP1) inhibitors have shown to avoid platin-induced nephrotoxicity without compromising its anticancer efficiency. The objective of this study was to describe DPEP1 expression in rat DRG in health and in early stages of oxaliplatin toxicity. To this end, we produced and characterized anti-DPEP1 polyclonal antibodies and used them to define the expression, and cellular and subcellular localization of DPEP1 by immunohistochemical confocal microscopy studies in healthy controls and short term (six days) oxaliplatin treated rats. RESULTS: DPEP1 is expressed mostly in neurons and in glia, and to a lesser extent in endothelial cells. Rats undergoing oxaliplatin treatment developed allodynia. TNF-𝛼 expression in DRG revealed a pattern of focal and at different intensity levels of neural cell inflammatory damage, accompanied by slight variations in DPEP1 expression in endothelial cells and in nuclei of neurons. CONCLUSIONS: DPEP1 is expressed in neurons, glia and endothelial cells of DRG. Oxaliplatin caused allodynia in rats and increased TNF-α expression in DRG neurons. The expression of DPEP1 in neurons and other cells of DRG suggest this protein as a novel strategic molecular target in the prevention of oxaliplatin-induced acute neurotoxicity.

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Introducción: Emicizumab es el primer tratamiento no sustitutivo para profilaxis en hemofilia A grave. Objetivos: Describir los resultados de nuestros pacientes en profilaxis con emicizumab, según la práctica clínica habitual. Material y métodos: Seguimiento de 13 pacientes desde el inicio de la profilaxis, registro de hemorragias, cirugías, reacciones adversas y necesidad o no de tratamiento factorial. Se midieron los niveles plasmáticos en las visitas de seguimiento; la técnica ha sido coagulativa en una etapa, modificada mediante dilución 1:20. Resultados: La mediana de niveles plasmáticos fue de 52,2mg [30,7-71,9]. La profilaxis resultó segura y eficaz; solamente se contabilizó una hemorragia espontánea a lo largo del tiempo y no precisó tratamiento. No hubo episodios tromboembólicos ni reacciones graves de hipersensibilidad, anafilaxia o anafilactoides. La incidencia de reacciones en el lugar de la inyección fue del 8%. El abordaje perioperatorio en las intervenciones menores se llevó a cabo sin tratamiento factorial coadyuvante, en 2 cirugías mayores se precisó una dosis de concentrado de FVIII plasmático en el paciente con hemofilia A sin inhibidor y FVII en el paciente con inhibidor, y fue suficiente para parar la hemorragia. Conclusión: Este estudio demostró que la farmacocinética de emicizumab y su vida media aseguran niveles óptimos con tratamiento profiláctico a las dosis establecidas en la ficha técnica.(AU)

Introduction: Emicizumab is the first non-replacement therapy for prophylaxis in severe hemophilia A. Aims: The principal aim of this study is to describe the results of our patients in prophylaxis with emicizumab, according to the usual clinical practice. Material and methods: Follow-up of 13 patients from the start of prophylaxis, recording of bleeding, surgeries, adverse reactions and the need or not for factor therapy. Plasma levels were measured at follow-up visits, the technique was coagulative in one stage, modified by 1:20 dilution. Results: Median plasma levels were 52.2mg [30.7–71.9]. Prophylaxis was safe and effective; only one spontaneous haemorrhage was recorded over time and no treatment was required. There were no thromboembolic events or serious hypersensitivity, anaphylaxis or anaphylactoid reactions. The incidence of injection site reactions was 8%. Perioperative management in minor interventions was carried out without adjuvant factorial therapy, in 2 major surgeries a dose of plasmatic FVIII concentrate was required in the patient with hemophilia A without inhibitor and FVII in the patient with inhibitor, and it was sufficient to stop the bleeding. Conclusion: This study demonstrated emicizumab pharmacokinetics and its half life ensure optimal levels with prophylaxis treatment at doses established in the technical data sheet.(AU)

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INTRODUCTION: Emicizumab is the first non-replacement therapy for prophylaxis in severe hemophilia A. AIMS: The principal aim of this study is to describe the results of our patients in prophylaxis with emicizumab, according to the usual clinical practice. MATERIAL AND METHODS: Follow-up of 13 patients from the start of prophylaxis, recording of bleeding, surgeries, adverse reactions and the need or not for factor therapy. Plasma levels were measured at follow-up visits, the technique was coagulative in one stage, modified by 1:20 dilution. RESULTS: Median plasma levels were 52.2mg [30.7-71.9]. Prophylaxis was safe and effective; only one spontaneous haemorrhage was recorded over time and no treatment was required. There were no thromboembolic events or serious hypersensitivity, anaphylaxis or anaphylactoid reactions. The incidence of injection site reactions was 8%. Perioperative management in minor interventions was carried out without adjuvant factorial therapy, in 2 major surgeries a dose of plasmatic FVIII concentrate was required in the patient with hemophilia A without inhibitor and FVII in the patient with inhibitor, and it was sufficient to stop the bleeding. CONCLUSION: This study demonstrated emicizumab pharmacokinetics and its half life ensure optimal levels with prophylaxis treatment at doses established in the technical data sheet.

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