Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (Camellia sinensis), has shown cancer preventive activity in animal models. The bioavailability of EGCG in the most commonly used animal species, mice, is poorly understood. Moreover, the pharmacokinetic parameters of EGCG have not been reported previously in mice. Here we report that after administration of EGCG intravenously at 21.8 micro mol/kg or intragastrically at 163.8 micro mol/kg, the peak plasma levels of EGCG in male CF-1 mice were 2.7 +/- 0.7 and 0.28 +/- 0.08 micro mol/L, respectively. EGCG was present mainly (50-90%) as the glucuronide. The plasma bioavailability of EGCG after intragastric administration was higher than previously reported in rats (26.5 +/- 7.5% vs. 1.6 +/- 0.6%). The conjugated EGCG displayed a shorter t(1/2) (82.8-211.5 vs 804.9-1102.3 min) than unconjugated EGCG (P < 0.01, Student's t test). EGCG was present in the unconjugated form in the lung, prostate and other tissues at levels of 0.31-3.56 nmol/g after intravenous administration. Although intragastric administration resulted in lower levels in most tissues compared with intravenous administration (e.g., 0.006 +/- 0.004 vs. 2.66 +/- 1.0 nmol/g in the lung), the levels in the small intestine and colon were high at 45.2 +/- 13.5 and 7.86 +/- 2.4 nmol/g, respectively. This is the first report of the pharmacokinetic parameters of EGCG in mice. Such information provides a basis for understanding the bioavailability of EGCG in mice and should aid in understanding the cancer preventive activity of EGCG.
Xenobiotic-induced liver injury is a clinically important etiology of hepatic disease that, if not recognized, can lead to hepatic failure. In this article we discuss the mechanisms of xenobiotic-induced liver injury, various factors that can alter the risk and severity of injury, the clinical and laboratory manifestations of injury, and the methods used to detect the presence of injury and (or) functioning liver mass.
Normal volunteers received single doses of recombinant human interleukin-10 (rhIL-10; n = 6 per group) or placebo (n = 3 per group) by intravenous injection to characterize pharmacokinetics, tolerability, and immunomodulatory effects. Dosages were 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 25.0, 50.0, and 100.0 micrograms/kg. Dose-related adverse effects consisted of a mild-to-moderate flu-like syndrome characterized by fever with chills, headache, and myalgias at the highest dose. The mean terminal phase t1/2 ranged from 2.3 +/- 0.5 to 3.7 +/- 0.8 hours. Dose-related effects of rhIL-10 included transient increases of circulating neutrophils and monocytes and decreases of lymphocytes. rhIL-10 markedly suppressed, in a time- and dose-dependent manner, the synthesis of the inflammatory cytokines IL-1 beta and tumor necrosis factor alpha by whole blood stimulated ex vivo with bacterial lipopolysaccharide. Circulating numbers of CD14+/HLA-DR+ cells at 24 hours after the dose were increased in a dose-dependent manner. Effects on expression of HLA-DR by CD14+ cells were variable. There was no apparent effect on HLA-DR expression by CD20+ cells. The immunomodulatory effects of rhIL-10 merit further clinical investigation.
Background:
We describe the temporal pattern of COVID-19 admissions to a tertiary care children’s hospital in central New Jersey during the SARS-CoV-2 surge, covering the time period from March 29 to July 26, 2020.
Methods:
Medical charts were reviewed for the date of admission, past medical history, and demographic variables, presenting signs and symptoms, admitting laboratory values, diagnostic imaging, diagnosis, treatment modalities, and outcomes including length of stay and disease severity.
Results:
Patients with symptomatic SARS-CoV-2 infection tended to present with pneumonia early during the study period, which coincided with the early surge in New Jersey cases. Approximately 2 weeks after the peak in reported SARS-CoV-2 cases in New Jersey, we began to see fewer pneumonia cases and an increase in admissions for Multi-Inflammatory Syndrome in Children and cases of acute appendicitis in association with a diagnosis of SARS-CoV-2 infection.
Conclusions:
We present a novel association of acute appendicitis in children infected with SARS-CoV-2 and postulate that it may represent a postinfectious hyperinflammatory complication of SARS-CoV-2 infection occurring 2 weeks after the early manifestation of acute pneumonia disease in children.
Clarithromycin is as effective in vivo as erythromycin, with less gastrointestinal irritation. Additionally, clarithromycin appears to expand the traditional spectrum of macrolide antibiotics, with promising activity against M. leprae and MAI.
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