A Case-Control Study of Involvement of Oxidative DNA Damage and Alteration of Antioxidant Defense System in Patients with Basal Cell Carcinoma: Modulation by Tumor Removal.

Oxidative damage has been suggested to play a role in the pathogenesis of basal cell carcinoma (BCC). This study illustrated an involvement of oxidative DNA damage and changes in antioxidant defenses in BCC by conducting a case-control study (24 controls and 24 BCC patients) and assessing urinary 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dGuo), plasma antioxidant defenses including catalase (CAT), glutathione peroxidase (GPx), NQO1, and total superoxide dismutase (SOD) activities, and glutathione (GSH) levels before surgery and 1 month after surgery. 8-oxo-dGuo expressions as well as protein and mRNA expressions of DNA repair enzyme hOGG1 and antioxidant defenses (CAT, GCLC, GPx, Nrf2, and MnSOD) in nonneoplastic epidermis of control and BCC tissues were also determined. This study observed induction in urinary 8-oxo-dGuo, increased 8-oxo-dGuo expression, and reduced hOGG1 protein and mRNA in BCC tissues, decreased activities of CAT, GPx, and NQO1, but elevated SOD activities and GSH levels in BCC patients and reduction of all antioxidant proteins and genes studied in BCC tissues. Furthermore, decreased plasma antioxidant activities in BCC patients were restored at 1 month after operation compared with preoperative levels. Herein, we concluded that BCC patients were associated with oxidative DNA damage and depletion of antioxidant defenses and surgical removal of BCC correlated with improved redox status.

Activation of indoleamine 2,3-dioxygenase in patients with scrub typhus and its role in growth restriction of Orientia tsutsugamushi.

BACKGROUND: Our earlier genome-wide expression study revealed up-regulation of a tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO1), in patients with scrub typhus. This gene has been previously reported to have anti-microbial activity in a variety of infectious diseases; therefore, we aimed to prove whether it is also involved in host defense against Orientia tsutsugamushi (OT) infection. METHODOLOGY/PRINCIPAL FINDINGS: Using LC-MS, we observed an increased ratio of serum L-kynurenine to serum L-tryptophan in patients with scrub typhus, which suggests an active catalytic function of this enzyme upon the illness. To evaluate the effect of IDO1 activation on OT infection, a human macrophage-like cell line THP-1 was used as a study model. Although transcription of IDO1 was induced by OT infection, its functional activity was not significantly enhanced unless the cells were pretreated with IFN-γ, a potent inducer of IDO1. When the degree of infection was evaluated by quantitative real-time PCR, the relative number of OT 47 kDa gene per host genes, or infection index, was markedly reduced by IFN-γ treatment as compared to the untreated cultures at five days post-infection. Inhibition of IDO1 activity in IFN-γ treated cultures by 1-methyl-L-tryptophan, a competitive inhibitor of IDO1, resulted in partial restoration of infection index; while excessive supplementation of L-tryptophan in IFN-γ treated cultures raised the index to an even higher level than that of the untreated ones. Altogether, these data implied that IDO1 was partly involved in restriction of OT growth caused by IFN-γ through deprivation of tryptophan. CONCLUSIONS/SIGNIFICANCE: Activation of IDO1 appeared to be a defensive mechanism downstream of IFN-γ that limited intracellular expansion of OT via tryptophan depletion. Our work provided not only the first link of in vivo activation of IDO1 and IFN-γ-mediated protection against OT infection but also highlighted the promise of this multifaceted gene in scrub typhus research.

Effect of Ayurved Siriraj herbal recipe Chantaleela on platelet aggregation.

INTRODUCTION: Ayurved Siriraj Chantaleela recipe is a traditional Thai remedy consisting of eight medicinal plants, which is employed for the treatment of fever. OBJECTIVE: To investigate the effects of Ayurved Siriraj Herbal recipe Chantaleela on platelet aggregation. STUDY DESIGN: Clinical research; ex vivo with before and after study design. MATERIAL AND METHOD: Twelve healthy male and female volunteers participated in the present study. Platelet aggregation test before Chantaleela ingestion was done as a control. After administration of 750 mg Chantaleela (3 x 250 mg tablets) every 8 hours for 3 doses, platelet aggregation was measured 8 hours following the first dose using an aggregometer and microplate reader. Adrenaline (Adr) and adenosine diphosphate (ADP) were used as platelet stimulants. Platelet aggregation was measured again at 32 hours and 8-10 days after the first dose. RESULTS: All of the participants completed the present study without any adverse event. Ayurved Siriraj Chantaleela did not affect platelet aggregation; neither Adr nor ADP were used as platelet agonists in both aggregometer and microplate reader Subgroup analysis revealed no significant change in platelet aggregation after Chantaleela administration according to the control for both male and female groups. The same results were also obtained in other subgroup analysis including hyperaggregation group, hypo-normal aggregation group. CONCLUSION: From the present study, normal dose of Chantaleela for alleviation of fever does not have an effect on either platelet aggregation or platelet numbers. It may conclude that the present study supports the safety use of Chantaleela for relieving fever as platelet status does not need to be taken into consideration.