RESUMEN
Introduction: Exceedingly high levels of the chemokine CCL5/RANTES have been found in fatty degenerated osteonecrotic alveolar bone cavities (FDOJ) and aseptic ischemic osteolysis of the jaw (AIOJ) from toothless regions. Because CCL5/RANTES seems to have a prominent role in creating the COVID-19 "cytokine storm", some researchers have used the monoclonal antibody Leronlimab to block the CCR5 on inflammatory cells.Objective: Is preexisting FDOJ/AIOJ jaw marrow pathology a "hidden" co-morbidity affecting some COVID-19 infections? To what extent does the chronic CCL5/RANTES expression from preexisting FDOJ/AIOJ areas contribute to the progression of the acute cytokine storm in COVID-19 patients?Methods: Authors report on reducing the COVID-19 "cytokine storm" by treating infected patients through targeting the chemokine receptor 5 (CCR5) with Leronlimab and interrupting the activation of CCR5 by high CCL5/RANTES signaling, thus dysregulating the inflammatory phase of the viremia. Surgical removal of FDOJ/AIOJ lesions with high CCL5/RANTES from patients with inflammatory diseases may be classified as a co-morbid disease.Results: Both multiplex analysis of 249 FDOJ/AIOJ bone tissue samples as well as serum levels of CCL5/RANTES displayed exceedingly high levels in both specimens.Discussion: By the results the authors hypothesize that chronic CCL5/RANTES induction from FDOJ/AIOJ areas may sensitize CCR5 throughout the immune system, thus, enabling it to amplify its response when confronted with the virus. As conventional intraoral radiography does little to assess the quality of the alveolar bone, ultrasonography units are available to help dentists locate the FDOJ/AIOJ lesions in an office setting.Conclusion: The authors propose a new approach to containment of the COVID-19 cytokine storm by a prophylactic focus for future viral-related pandemics, which may be early surgical clean-up of CCL5/RANTES expression sources in the FDOJ/AIOJ areas, thus diminishing a possible pre-sensitization of CCR5. A more complete dental examination includes trans-alveolar ultrasono-graphy (TAU) for hidden FDOJ/AIOJ lesions.
Asunto(s)
COVID-19 , Quimiocina CCL5 , Humanos , COVID-19/inmunología , COVID-19/epidemiología , Comorbilidad , Masculino , Femenino , Persona de Mediana Edad , Receptores CCR5/metabolismo , Anciano , Enfermedades Maxilomandibulares/epidemiología , Enfermedades Maxilomandibulares/inmunología , SARS-CoV-2 , Síndrome de Liberación de Citoquinas , Anticuerpos Monoclonales Humanizados/uso terapéutico , AdultoRESUMEN
OBJECTIVE: We hypothesized that, similar to idiopathic hip osteonecrosis, the T-786C mutation of the endothelial nitric oxide synthase (eNOS) gene affecting nitric oxide (NO) production was associated with neuralgia-inducing cavitational osteonecrosis of the jaws (NICO). DESIGN: In 22 NICO patients, not having taken bisphosphonates, mutations affecting NO production (eNOS T-786C, stromelysin 5A6A) were measured by polymerase chain reaction. Two healthy normal control subjects were matched per case by race and gender. RESULTS: Homozygosity for the mutant eNOS allele (TT) was present in 6 out of 22 patients (27%) with NICO compared with 0 out of 44 (0%) race and gender-matched control subjects; heterozygosity (TC) was present in 8 patients (36%) versus 15 control subjects (34%); and the wild-type normal genotype (CC) was present in 9 patients (36%) versus 29 controls (66%) (P = .0008). The mutant eNOS T-786C allele was more common in cases (20 out of 44 [45%]) than in control subjects (15 out of 88 [17%]) (P = .0005). The distribution of the stromelysin 5A6A genotype in cases did not differ from control subjects (P = .13). CONCLUSIONS: The eNOS T-786C polymorphism affecting NO production is associated with NICO, may contribute to the pathogenesis of NICO, and may open therapeutic medical approaches to treatment of NICO through provision of L-arginine, the amino-acid precursor of NO.
Asunto(s)
Citosina , Enfermedades Maxilomandibulares/genética , Neuralgia/etiología , Óxido Nítrico Sintasa de Tipo III/genética , Osteonecrosis/genética , Polimorfismo Genético/genética , Timina , Adenina , Adulto , Alelos , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Genotipo , Heterocigoto , Homocigoto , Humanos , Masculino , Metaloproteinasa 3 de la Matriz/genética , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios ProspectivosAsunto(s)
Médula Ósea , Edema/inducido químicamente , Osteonecrosis/inducido químicamente , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Edema/patología , Humanos , Isquemia/diagnóstico , Osteonecrosis/diagnóstico por imagen , Osteonecrosis/patología , Radiografía , Odontalgia/etiologíaAsunto(s)
Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Predisposición Genética a la Enfermedad , Enfermedades Maxilomandibulares/inducido químicamente , Osteonecrosis/inducido químicamente , Fibrinólisis/genética , Humanos , Factores de Riesgo , Trombofilia/complicaciones , Trombofilia/genética , Trombosis/etiología , Trombosis/genéticaRESUMEN
The scientific and diagnostic status of neuralgia-inducing cavitational osteonecrosis, NICO, has not been definitively established. A case is presented in favor of this diagnosis based on published literature. It is argued that the case against NICO has been made largely based on personal experiences, by innuendo, and through personal attacks rather than in scientific debate.