Smoking is associated with a variety of changes in the oral cavity. Cigarette smoke has effects on saliva, oral commensal bacteria and fungi, mainly Candida, which causes oral candidosis, the most common opportunistic fungal infection in man. How cigarette smoke affects oral Candida is still controversial. This brief overview is an attempt to address the clinical findings on the relationship between smoking and oral candidosis and possible mechanisms of pathogenicity.

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It has been reported that poor glycaemic control predisposes to oral candidal infection in diabetic patients. For instance, the carriage of Candida species and the density of candidal growth in the oral cavity is frequently claimed to be increased in patients with diabetes mellitus. However, the validity of these observations remains controversial. Hence, we review and discuss here the clinical data in the literature on the relationship between diabetes and oral candidal carriage and infection, and possible mechanisms associated with its pathogenicity.

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The alternative NF-kB pathway consists predominantly of NF-kB-inducing kinase (NIK), IkB kinase a (IKKa), p100/p52, and RelB. The hallmark of the alternative NF-kB signaling is the processing of p100 into p52 through NIK, thus allowing the binding of p52 and RelB. The physiologic relevance of alternative NF-kB activation in bone biology, however, is not well understood. To elucidate the role of the alternative pathway in bone homeostasis, we first analyzed alymphoplasic (aly/aly) mice, which have a defective NIK and are unable to process p100, resulting in the absence of p52. We observed increased bone mineral density (BMD) and bone volume, indicating an osteopetrotic phenotype. These mice also have a significant defect in RANKL-induced osteoclastogenesis in vitro and in vivo. NF-kB DNAbinding assays revealed reduced activity of RelA, RelB, and p50 and no binding activity of p52 in aly/aly osteoclast nuclear extracts after RANKL stimulation. To determine the role of p100 itself without the influence of a concomitant lack of p52, we used p100 À/À mice, which specifically lack the p100 inhibitor but still express p52. p100 À/À mice have an osteopenic phenotype owing to the increased osteoclast and decreased osteoblast numbers that was rescued by the deletion of one allele of the relB gene. Deletion of both allele of relB resulted in a significantly increased bone mass owing to decreased osteoclast activity and increased osteoblast numbers compared with wildtype (WT) controls, revealing a hitherto unknown role for RelB in bone formation. Our data suggest a pivotal role of the alternative NF-kB pathway, especially of the inhibitory role of p100, in both basal and stimulated osteoclastogenesis and the importance of RelB in both bone formation and resorption. ß

Bone degenerative diseases, including osteoporosis, impair the fine balance between osteoclast bone resorption and osteoblast bone formation. Single-agent therapy for anabolic and anticatabolic effects is attractive as a drug target to ameliorate such conditions. Inhibition of nuclear factor (NF)-κB reduces the osteoclast bone resorption. The role of NF-κB inhibitors on osteoblasts and bone formation, however, is minimal and not well investigated. Using an established NF-κB inhibitor named S1627, we demonstrated that inhibition of NF-κB increases osteoblast differentiation and bone formation in vitro by up-regulating the mRNAs of osteoblast-specific genes like type I collagen, alkaline phosphatase, and osteopontin. In addition, S1627 was able to increase bone formation and repair bone defect in a murine calvarial defect model. To determine the effect of NF-κB on a model of osteoporosis, we injected two doses of inhibitor (25 and 50 mg/kg·d) twice a day in sham-operated or ovariectomized 12-wk-old mice and killed them after 4 wk. The anabolic effect of S1627 on trabecular bone was determined by micro focal computed tomography and histomorphometry. Bone mineral density of inhibitor-treated ovariectomized animals was significantly increased compared with sham-operated mice. Osteoblast-related indices like osteoblast surface, mineral apposition rate, and bone formation rate were increased in S1627-treated animals in a dose-dependent manner. NF-κB inhibition by S1627 increased the trabecular bone volume in ovariectomized mice. Furthermore, S1627 could inhibit the osteoclast number, and osteoclast surface to bone surface. In vitro osteoclastogenesis and bone resorbing activity were dose-dependently reduced by NF-κB inhibitor S1627. Taken collectively, our results suggest that NF-κB inhibitors are effective in treating bone-related diseases due to their dual anabolic and antiresorptive activities.

Oral candidosis (syn. Oral candidiasis; OC), is a collective term given to a group of oral mucosal disorders caused by the fugal pathogen belonging to the genus Candida. The association of OC with the human immunodeficiency virus (HIV) infection has been known since the advent of the acquired immune deficiency syndrome (AIDS) pandemic. OC is one of the earliest manifestations of HIV disease in high risk individuals not undergoing chemotherapy and is also a strong predictor of the subsequent risk of AIDS-related illness or death. With the advances in HIV therapy, such as highly active anti-retroviral therapy (HAART), the prevalence and presenting features of OC have changed in HIV-infected individuals, especially those in industrialized countries. The presence of OC in "controlled" HIV-positive individuals may be indicative of a patient nonadherence to therapy or possible failure. The factors contributing to the genesis of OC and its progression in these individuals are poorly understood, but may include an interrelationship between HIV and Candida and/or a dysfunction in the local immunity, superimposed on weakened cell-mediated immunity and depletion of CD4 T cells. The dramatic increase in publications on this topic matches the increased importance and awareness of this opportunistic infection in HIV-infected individuals. In this review we first address the epidemiologic and clinical features of OC in HIV-infected persons, followed by the current understanding of the pathogenesis of OC in the context of HIV infection with a concluding section on the current management concepts of OC.

The advent of the human immunodeficiency virus infection and the increasing prevalence of compromised individuals in the community due to modern therapeutic advances have resulted in a resurgence of opportunistic infections, including oral candidosis, which is by far the most common oral fungal infection in man. Broad-spectrum antibiotics used in the treatment of a wide range of disease conditions have also been attributed as a predisposing factor of oral candidosis. In this mini review we discuss the research findings on the relationship between antibiotics and oral candidosis and possible mechanisms of pathogenicity following such therapy.