A new approach at diabetic foot treatment: Phosphodiesterase 5 inhibitors

Bugday, Muhammet Serdar; Oksuz, Ersoy

doi:10.1016/j.mehy.2020.109694

Cited by 3 publications

(4 citation statements)

References 14 publications

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“…Inhibition of PDEs increases the cellular levels of cyclic nucleotides, thereby ensures sustained activation of the respective signaling events. The potential use of PDE inhibitors has also been implicated for diabetes, Alzheimer’s disease, prostate cancer, colorectal cancer, cognitive enhancement, long-term memory deficits, and tuberculosis. − For these reasons, the development of PDE inhibitors has remained an active research area.…”

Section: Introductionmentioning

confidence: 99%

Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting α-Helix Backbone Oxygen by Halogen Bonding

et al. 2020

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Phosphodiesterase 5A1 (PDE5) is a key target for treating cardiovascular diseases and erectile dysfunction. Here, we report the crystal structure of PDE5 complexed with the sole second generation drug avanafil. Analysis of protein–drug interactions revealed the structural basis of avanafil’s superior isoform selectivity. Moreover, a halogen bonding was observed between avanafil and a backbone carbonyl oxygen of an adjacent α-helix, whose contribution to inhibitory potency illustrates the feasibility of exploiting α-helix backbone in structure-based drug design.

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Section: Introductionmentioning

confidence: 99%

Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting α-Helix Backbone Oxygen by Halogen Bonding

et al. 2020

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“…Desde el punto de vista fisiopatológico, el entumecimiento en personas con diabetes frecuentemente representa la pérdida de la sensación protectora por lesión en las fibras nerviosas largas (Boulton), lo que puede incrementar el riesgo de ulceración por deficiencia del sistema inmune y vascular (34). Varios autores han demostrado relación entre la neuropatía y desarrollo de úlceras en los pies (35)(36)(37).…”

Section: Discussionunclassified

Perfil de riesgo de los pies de personas con diabetes tipo 2 y factores asociados

Pereira Olmos,

Dueñas Espín,

Goyes Ayala

et al. 2023

Cienc. Serv. Salud Nutr.

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Introducción: A nivel mundial se recomienda la revisión de los pies de las personas con diabetes para detectar riesgo de complicaciones. Objetivo: Identificar el nivel de riesgo de los pies de personas con diabetes y sus factores asociados. Metodología: Estudio de corte transversal. Fueron evaluadas personas con diabetes mellitus tipo 2, mediante encuesta y evaluación clínica, se estratificó a las personas de acuerdo con la escala de valoración del riesgo de complicaciones en los pies del Grupo Internacional de Trabajo en Pie Diabético. Análisis de regresión logística multivariante evaluaron la asociación entre las variables. Resultados: Se asociaron a un mayor riesgo de complicaciones: el ser mujer, la edad, ser fumador, no tener registrada una evaluación neurológica de los pies y presentar antecedente de entumecimiento en los pies. Mientras que menor riesgo se asoció al hecho de no tener hallazgos patológicos en los pies, mayor nivel de conocimientos de los pacientes en relación con el cuidado de los pies y estar tomando hipoglucemiantes orales. Conclusiones: Cerca de las dos terceras partes de las personas con diabetes presentaron algún nivel de riego para sus pies.

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“…Over the past several years, NO has been proved to play an important role in the wound healing 81 . Not only does NO supports the endothelial cell proliferation but also collagen synthesis and epithelisation 82 .…”

Section: Pde5i and Wound Healingmentioning

confidence: 99%

“…Over the past several years, NO has been proved to play an important role in the wound healing. 81 Not only does NO supports the endothelial cell proliferation but also collagen synthesis and epithelisation. 82 Furthermore, angiogenesis, which promotes wound tensile strength and plays a vital role in tissue repair, is dependent on the NO‐cyclic GMP axis.…”

Section: Pde5i and Wound Healingmentioning

confidence: 99%

The efficacy of PDE5 inhibitors in diabetic patients

Święcicka

2022

Andrology

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Background: Phosphodiesterase 5 inhibitors (PDE5i), since their introduction in the late 1990s, have proven their efficacy in treating several conditions, predominantly pulmonary hypertension and erectile dysfunction where they remain the first-line therapeutic option. However, in the recent years, growing evidence from both animal and human studies has emerged to suggest the additional benefits of PDE5i in cardiovascular and metabolic disorders. This is of specific interest to the diabetes population where prevalent cardiovascular disease and metabolic dysregulation significantly contribute to the increased morbidity and mortality. Objectives:To examine the available data on the non-standard, pleiotropic effects of PDE5i in patients with diabetes mellitus. Materials and methods:The review of the published background research, preclinical studies and clinical trials. Results:In human studies, PDE5 inhibition appeared to be associated with reduced cardiovascular mortality and overall improved clinical outcomes in those with established cardiovascular disease. PDE5i were also consistently found to reduce albuminuria in subjects with diabetic nephropathy. Furthermore, animal data suggest a plausible effect of this group of medication on sensory function and neuropathic symptoms in diabetic neuropathy as well as improved wound healing. A decrease in insulin resistance and augmentation of beta cell function seen in preclinical studies has not been consistently demonstrated in human trials. Discussion and conclusion:In animal models, PDE5 inhibition appears to decrease oxidative stress and reduce some of the micro-and macrovascular complications associated with diabetes. However, data from human trials are limited and largely inconsistent, highlighting the need for adequately powered, randomised-controlled trials in diabetic cohorts in order to fully assess the benefits of PDE5i in this group of patients.

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A new approach at diabetic foot treatment: Phosphodiesterase 5 inhibitors

Cited by 3 publications

References 14 publications

Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting α-Helix Backbone Oxygen by Halogen Bonding

Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting α-Helix Backbone Oxygen by Halogen Bonding

Perfil de riesgo de los pies de personas con diabetes tipo 2 y factores asociados

The efficacy of PDE5 inhibitors in diabetic patients

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