Objective. The aim of this study was to determine the incidence and bacteriology of bacteremia associated with various oral and maxillofacial surgical procedures. Methods.A total of 237 patients who underwent oral and maxillofacial surgery were included in this study. Blood samples were obtained for bacteriological examination immediately after the essential steps of the surgical procedure had been performed.Results. Bacteremia was detected in patients who underwent surgery for tumor, infection and trauma, and surgical reconstruction of jaw. In particular, decortication for osteomyelitis and tooth extraction resulted in a higher incidence of bacteremia compared with other surgical procedures. The incidence of bacteremia was not affected by oral hygiene, gingival inflammation, blood loss and duration of surgery. Furthermore, concerning tooth extraction, there was no statistical difference in the incidence of bacteremia with respect to the number of teeth extracted and the method of extraction.Extraction of teeth with odontogenic infection (periodontitis, periapical infection and pericoronitis) did however produce a significantly increased incidence of bacteremia compared with infection-free teeth (P<0.01).Viridans streptococci were the predominant group of bacteria isolated from the bacteremias. Conclusion.Oral and maxillofacial surgery involving trans-oral incision produces bacteremia, regardless of the extent and degree of surgical invasion. In particular, surgical procedure at infected sites is more likely to result in bacteremia compared with infection-free sites.

Drug-induced liver injury is a major safety concern in drug development and clinical pharmacotherapy; however, advances in the understanding of the mechanisms of drug-induced liver injury are hampered by the lack of animal models. Carbamazepine (CBZ) is a widely used antiepileptic agent. Although the drug is generally well tolerated, only a small number of patients prescribed CBZ develop severe hepatitis. In the present study, we developed a mouse model of CBZ-induced liver injury and elucidated the mechanisms accounting for the hepatotoxicity of CBZ. Male BALB/c mice were orally administered CBZ for 5 days. The plasma levels of alanine aminotransferase and aspartate aminotransferase were prominently increased, and severe liver damage was observed via histological evaluation. The analysis of the plasma concentration of CBZ and its metabolites demonstrated that 3-hydroxy CBZ may be relevant in CBZ-induced liver injury. The hepatic glutathione levels were significantly decreased, and oxidative stress markers were significantly altered. Mechanistic investigations found that hepatic mRNA levels of toll-like receptor 4, receptor for advanced glycation end products, and their ligands were significantly increased. Moreover, the plasma concentrations of proinflammatory cytokines were also increased. Prostaglandin E(1) administration ameliorated the hepatic injury caused by CBZ. In conclusion, metabolic activation followed by the stimulation of immune responses was demonstrated to be involved in CBZ-induced liver injury in mice.

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Drug-induced liver injury (DILI) is the most frequent cause of post-marketing warnings and withdrawals. Amiodarone (AMD), an antiarrhythmic, presents a risk of liver injury in humans, and its metabolites, formed by cytochrome P450 3A4, are likely more toxic to hepatocytes than AMD is. However, it remains to be clarified whether the metabolic activation of AMD is involved in liver injury in vivo. In this study, to elucidate the underlying mechanisms of AMD-induced liver injury, mice were administered AMD [1000 mg kg(-1), per os (p.o.)] after pretreatment with dexamethasone [DEX, 60 mg kg(-1), intraperitoneal (i.p.)], which induces P450 expression, once daily for 3 days. The plasma alanine aminotransferase (ALT) levels were significantly increased by AMD administration in the DEX-pretreated mice, and the liver concentrations of desethylamiodarone (DEA), a major metabolite of AMD, were correlated with the changes in the plasma ALT levels. Cytochrome c release into the hepatic cytosol and triglyceride levels in the plasma were increased in DEX plus AMD-administered mice. Furthermore, the ratio of reduced glutathione to oxidized glutathione disulfide in the liver significantly decreased in the DEX plus AMD-administered mice. The increase of ALT levels was suppressed by treatment with gadolinium chloride (GdCl3 ), which is an inhibitor of Kupffer cell function. From these results, it is suggested that AMD and/or DEA contribute to the pathogenesis of AMD-induced liver injury by producing mitochondrial and oxidative stress and Kupffer cell activation. This study proposes the mechanisms of AMD-induced liver injury using an in vivo mouse model.

Drug-induced liver injury (DILI) is a serious problem in pre-clinical stages of drug development and clinical pharmacotherapy, but the pathogenesis of DILI has not been elucidated. Flucloxacillin (FLX), which is a β-lactam antibiotic of the penicillin class that is used widely in Europe and Australia, rarely causes DILI. Clinical features suggest that FLX-induced liver injury is caused by immune- and inflammatory-related factors, but the mechanism of FLX-induced liver injury is unknown. The purpose of this study was to elucidate the mechanisms of FLX-induced liver injury in vivo. Plasma alanine aminotransferase, aspartate aminotransferase and total-bilirubin levels were significantly elevated in FLX-administered mice [1000 mg kg(-1) , intraperitoneally (i.p.)]. Toll-like receptor 4 (TLR4) ligands, such as high-mobility group box 1 (HMGB1) and S100A8/A9, were significantly increased in FLX-administered mice, and inflammatory factors, such as interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein (MIP)-2, CXC chemokine-ligand-1 (CXCL1) and monocyte chemoattractant protein (MCP)-1, were also significantly elevated. IL-17-related transcriptional factors and cytokines were increased, and the administration of recombinant IL-17 (2 mg per body weight, i.p.) resulted in an exacerbation of the FLX-induced liver injury. TLR4-associated-signal transduction may be involved in FLX-induced liver injury, and IL-17 is an exacerbating factor.

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