Background: The aim of this clinical trial was to evaluate the effects of febuxostat (FBX) in comparison with hydroxychloroquine (HCQ) on clinical symptoms, laboratory tests and chest CT findings in outpatients with moderate symptoms of COVID-19 infection. Methods: We conducted a clinical trial involving adult outpatients with the moderate respiratory illness following COVID-19 infection. Patients were randomly assigned to receive either FBX or HCQ for 5 days. The measured variables were needs to hospitalisation, clinical and laboratory data including fever, cough, breathing rate, C-Reactive Protein level, lymphocytes count at onset of admission and was well as at 5 days of treatments. In addition, CT findings were evaluated on admission and 14 days after initiation of treatment. Results: Sixty subjects were enrolled in the study with a 1 to 1 ratio in FBX and HCQ groups. On admission, fever (66.7%), cough (87%), tachypnoea (44.4%), dyspnoea (35%), elevated CRP value (94.4%) and lung involvement according to chest CT (100%) were documented in enrolled patients with insignificant difference between FBX and HCQ groups. Fever, cough and tachypnoea were significantly mitigated in both groups after five days of treatments without any significant differences between groups. The mean percentages of lung involvement were significantly reduced to 7.3% and 8% after 14 days of treatment with FBX and HCQ, respectively. In adult outpatients with moderate COVID-19 infection, the effectiveness of FBX and HCQ was not different in terms of resolution of clinical manifestations, laboratory tests and lung CT findings. Conclusion: This trial suggests that FBX is as an alternative treatment to HCQ for COVID-19 infection and may be considered in patients with a contraindication or precaution to HCQ.
Vitamin E consumption may be associated with a significant protective effect against radiation-induced dysfunction in salivary glands following single-dose ¹³¹I therapy in patients with differentiated thyroid cancer.
The high expression of the human epidermal growth factor receptor 2 (HER2) and the accessibility of its extracellular domain make it an ideal target for the targeted delivery of anti-tumor drugs as well as imaging agents. In this study, the heptapeptide leucine-threonine-valine-serine-proline-tryptophan-tyrosine (LTVSPWY) as a new small peptide for an anti-HER2 target was labeled by incorporating Tc to the cysteine-based ligands CGGG (Cys-Gly-Gly-Gly) and CSSS (Cys-Ser-Ser-Ser) linked to this peptide. BothTc-labeled peptides were evaluated for HER2 bindings as well as pharmacokinetics and tumor targeting. CGGG- and CSSS-LTVSPWY peptides were labeled with Tc using a gluconate ligand exchange. Cellular specific binding, affinities, and internalization of both peptides to the HER2 receptor were evaluated in the SKOV-3 cell line. Specific targeting of both peptides to the HER2 receptor was assessed in three cell lines with different levels of HER2 expression. Studies were performed in SKOV-3 tumor bearing mice for tumor targeting. Both peptides were labeled withTc with more than 99% efficiency and showed favorable stability in solution and serum. The HER2 binding affinities of both the radiolabeled peptides were inhibited up to 60% by the unlabeled peptide, as well as with trastuzumab antibody. We observed nanomolar binding affinities for both radiolabeled peptides. The tumor uptakes were 4.95 ± 4.84% and 3.84 ± 2.53% for the CSSS and CGGG chelators, respectively, at 1 h after injection. However, tumor uptakes were similar for both peptides at 4 h postinjection, although a higher tumor to background ratio and lower radioactivity retention in the kidney were observed for CSSS, leading to a clearer tumor image with injection of this peptide. These small new peptides were selectively targeted to the HER2 receptor, and introduction of a serine residue into the chelator improved the pharmacokinetics of Tc labeled LTVSPWY for clear tumor imaging in animals.
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