RESUMEN
The Omicron subvariants of SARS-CoV-2 have multiple mutations in the S-proteins and show high transmissibility. We previously reported that tea catechin (-)-epigallocatechin gallate (EGCG) and its derivatives including theaflavin-3,3'-di-O-digallate (TFDG) strongly inactivated the conventional SARS-CoV-2 by binding to the receptor binding domain (RBD) of the S-protein. Here we show that Omicron subvariants were effectively inactivated by green tea, Matcha, and black tea. EGCG and TFDG strongly suppressed infectivity of BA.1 and XE subvariants, while effect on BA.2.75 was weaker. Neutralization assay showed that EGCG and TFDG inhibited interaction between BA.1 RBD and ACE2. In silico analyses suggested that N460K, G446S and F490S mutations in RBDs crucially influenced the binding of EGCG/TFDG to the RBDs. Healthy volunteers consumed a candy containing green tea or black tea, and saliva collected from them immediately after the candy consumption significantly decreased BA.1 virus infectivity in vitro. These results indicate specific amino acid substitutions in RBDs that crucially influence the binding of EGCG/TFDG to the RBDs and different susceptibility of each Omicron subvariant to EGCG/TFDG. The study may suggest molecular basis for potential usefulness of these compounds in suppression of mutant viruses that could emerge in the future and cause next pandemic.
Asunto(s)
COVID-19 , Camellia sinensis , Catequina , Humanos , SARS-CoV-2/metabolismo , Té/química , Camellia sinensis/metabolismoRESUMEN
A 60-year-old man with multiple myeloma (MM) (IgG-kappa, stage IIIA) had been treated with minodronate at 6 mg orally as a phase 1 clinical trial for myeloma bone disease for 13 months (total dose, 4032 mg). Then he received incadronate at 10mg intravenously every 1 to 4 weeks (total dose, 350 mg). In July 2005, he complained of mild right mandibular pain, and bone scintigram showed a hot spot at the right side of the mandible. Panoramic radiograph showed osteonecrosis of the jaw (ONJ) and axial and 3-dimensional computed tomography confirmed ONJ. Oral examination showed massive gingival swelling of the right side of the mandible without exposed necrotic bone. He was given clarithromycin in addition to levofloxacin, followed by hyperbaric oxygen (HBO) therapy, which resulted in the complete disappearance of the pain. This is a first reported case of ONJ induced by incadronate. The present case suggests that early detection of ONJ by regular dental check-ups is important in the management of patients with MM who have received bisphosphonate therapy, and HBO in combination with antibiotic therapy is effective in the early stage of ONJ.
Asunto(s)
Antibacterianos/uso terapéutico , Difosfonatos/efectos adversos , Oxigenoterapia Hiperbárica , Enfermedades Maxilomandibulares , Mieloma Múltiple/complicaciones , Osteonecrosis/terapia , Diagnóstico por Imagen/métodos , Humanos , Enfermedades Maxilomandibulares/diagnóstico , Masculino , Mandíbula/patología , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Osteonecrosis/inducido químicamente , Osteonecrosis/diagnóstico , Dolor , Resultado del TratamientoRESUMEN
BACKGROUND: The objectives of this study were to evaluate the effect of the number of infused CD34+ cells on hematopoietic recovery and on the cost in autologous peripheral blood stem cell transplantation (PBSCT). METHODS: Sixty-nine patients who received autologous PBSCT (ABSCT) were divided into three groups defined by the number of infused CD34+ cells. The number of days until 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets, the number of transfused blood products, the febrile days, the duration of parenteral antibiotics and the cost of additional supportive care (transfusions of blood products and parenteral antibiotics) were analyzed. RESULTS: Twenty-three patients received <2.5 x 10(6)/kg of CD34+ cells (group A), 25 patients received > or = 2.5 to 5 x 10(6)/kg of CD34+ cells (group B) and 21 patients received > or = 5 x 10(6)/kg of CD34+ cells (group C). Patients in group C had rapid neutrophil (p < 0.01) and platelet (p < 0.05) recovery and required less platelet transfusions (p < 0.05) than patients in other groups. Transfusions of red blood cell concentrates, the duration of febrile days or parenteral antibiotics were not statistically different between the two groups. The patients in group C required significantly lower costs for platelet concentrates and additional supportive care (p < 0.05). CONCLUSION: Infusion of > or = 5 x 10(6)/kg of CD34+ cells in ABSCT shortens hematopoietic recovery and reduces costs for additional supportive care.