SummaryCandida albicans is the most common oral fungal pathogen of humans, but the mechanisms by which C. albicans invades and persists within mucosal epithelium are not clear. To understand oral pathogenesis, we characterized the cellular and molecular mechanisms of epithelial-fungus interactions using reconstituted human oral epithelium (RHE). We observed that hyphal formation facilitates epithelial invasion via both active (physical penetration) and passive (induced endocytosis) processes. Genome wide transcript profiling of C. albicans experimental RHE infection was compared with that from 11 patient samples with pseudomembranous candidiasis to identify genes associated with disease development in vivo. Expression profiles reflected the morphological switch and an adaptive response to neutral pH, non-glucose carbon sources and nitrosative stress. We identified several novel infection-associated genes with unknown function. One gene, upregulated in both RHE infection and patients, named EED1, was essential for maintenance of hyphal elongation. Mutants lacking EED1 showed transient cell elongation on epithelial tissue, which enabled only superficial invasion of epithelial cells. Once inside an epithelial cell, Deed1 cells could proliferate as yeasts or pseudohyphae but remained trapped intracellularly. Our results suggest that the adaptive response and morphology of C. albicans play specific roles for host-fungal interactions during mucosal infections.

In recent years the management of human immunodeficiency virus (HIV)-positive individuals has been based on highly active antiretroviral therapy (HAART) comprising a combination of nucleoside analogues or the combination of these agents with protease inhibitors. The aim of the present study was to describe the prevalence of oral lesions in a cohort of 103 HIV-seropositive patients on HAART, to compare these data with the prevalence of lesions prior to HAART and to correlate these finding with the immunologic data. A total of 103 HIV-seropositive patients on HAART were selected. Oral lesions associated with HIV infection and immunological parameters were registered. On re-examination 6 months after the first evaluation, 61/103 patients were available. Comparing the prevalence of oral lesions before and after the onset of HAART, the number of oral lesions was significantly lower (P=0.001). The number of CD4+ cells increased and the viral load decreased significantly after initiation of HAART (P=0.001 and P= 0.0001). On re-examination 6 months later, the prevalence of lesions again decreased significantly (P=0.001). The immunological benefits of HAART may prevent HIV-associated oral lesions in patients with advanced HIV disease. Our results showed that oral manifestations decrease on HAART, but in four patients the immunological effects of therapy did not provide sufficient protection against human papillomavirus (HPV)induced lesions.

Primary stability has a major impact on the long-term success of dental implants. The aim of this study was to investigate the correlation of resonance frequency analysis (RFA) and insertion torque of self-tapping and non-self-tapping implants and their respective differences in primary stability. A group of 263 patients were treated with a total of 602 conically formed dental implants: 408 non-self-tapping Ankylos and 194 self-tapping Camlog. The maximum insertion torque during implant placement was recorded. Resonance frequency, measured as the implant stability quotient (ISQ), was assessed once immediately after insertion and twice 3 months later. Torque values of the non-self-tapping implants were significantly higher than those in the self-tapping group (p = 0.023). RFA did not show differences between the 2 groups (p = 0.956), but a correlation between ISQ values after implantation and 3 months after implant placement was measured (r = 0.712). Within the implant systems, no correlation between insertion torque and resonance frequency values could be determined (r = 0.305). Our study indicates that the ISQ values obtained from different implant systems are not comparable. The RFA does not appear suitable for the evaluation of implant stability when used as a single method. Higher insertion torque of the non-self-tapping implants appeared to confirm higher clinical primary stability.

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The susceptibility of Candida albicans to a new antifungal triazole, voriconazole (UK-109,496), was investigated in 105 isolates obtained from the oral cavities of patients with human immunodeficiency virus (HIV) infection to study this drug's activity against fluconazole-susceptible and -resistant isolates. MICs were determined by a broth microdilution technique according to document M27-T from the National Committee for Clinical Laboratory Standards and by using a broth microdilution technique and a synthetic high-resolution medium. These antifungal susceptibility testing methods showed high levels of agreement (93% for fluconazole and 86% for voriconazole). Data from in vitro studies showed that voriconazole has good activity against fluconazole-susceptible and -resistant C. albicans isolates; the MICs at which 90% of all isolates were inhibited were 0.19 to 0.39 microgram/ml. We found that for isolates for which fluconazole MICs were high, voriconazole MICs were proportionally higher than those for fluconazole-susceptible C.albicans (P < 0.001). Pretreatment isolates from six patients with fluconazole-refractory esophageal candidiasis were included in the study. For these isolates the MICs were < or = 0.39 microgram/ml, and all patients responded to voriconazole. These results suggest that voriconazole is effective even in the treatment of fluconazole-refractory esophageal candidiasis and should be studied further to determine its clinical relevance in patients with HIV infection.

In this report, we describe a patient with recurrent episodes of oral candidosis who finally suffered from fluconazole-refractory oral and oesophageal candidosis. The patient was monitored for 4 years until his death from AIDS. During the observation period, persistent colonization with both Candida albicans and Candida dubliniensis was observed. From the appearance of the first episode of oral candidosis, the patient was treated with fluconazole for 18 months. The infection became unresponsive to fluconazole 400 mg/day. In vitro susceptibility testing revealed the development of resistance to fluconazole in C. albicans and C. dubliniensis. Molecular typing confirmed the persistence of the same C. albicans and C. dubliniensis strains which developed resistance after up to 3 years of asymptomatic colonization. This observation demonstrates that Candida spp. other than C. albicans may develop resistance to fluconazole in a patient who is repeatedly exposed to the drug.

A light and electron microscopic investigation of pseudomembranous candidiasis in HIV infection was undertaken as there is little data available on the ultrastructural features of the invasive phase of Candida in this disease. On examination of biopsy specimens of four patients, histopathology revealed the classic features of superficial candidiasis, including hyphal penetration down to the spinous cell layer, parakeratosis, acanthosis and spongiosis of the infected, superficial epithelium. However, in one case, hyphae traversed the entire epithelium and crossed the basal membrane, invading the adjacent connective tissue. Ultrastructural investigations revealed initial hyphal penetration through the intercellular spaces, possibly demonstrating thigmotropism. However, hyphal penetration was not solely confined to intercellular spaces, as some specimens demonstrated hyphal elements traversing both the cytoplasm and the nuclei of the spinous cells. In these areas of the epithelium appressoria-like appendages were often found at the hyphal tip. These phenomena, commonly described in plant fungi, have rarely been described in human material. Pools of desmosomes were seen in the vicinity of the hyphal pathways, implying that the penetration procedure is associated with detachment and congregation of desmosomes, possibly by enzymatic means. Interestingly, the host immune response to fungal invasion appeared to be minimal, as no immune-effector cells were seen closely associated with either the blastospores or the hyphae in any of the tissues examined. Whether the foregoing events are exaggerated by the abortive immune response seen in HIV-infected patients, or common in immunocompetent individuals during candidal invasion of epithelia, needs to be ascertained by further studies.

Background To give an overview on implant survival rates in patients with oral manifestations of systemic autoimmune (oral Lichen planus (oLp), Pemphigus (Pe)), muco-cutaneous (Epidermolysis bullosa (EB)), autoimmune multisystemic rheumatic diseases (Sjögren´s syndrome (SjS), systemic Lupus erythematosus (sLE), or systemic Sclerosis (sSc)). Material and Methods Systematic literature review (PubMed/Medline, Embase) using MESH and search term combinations, published between 1980 and August 2018 in English language reporting on dental implant-prosthetic rehabilitation of patients with oLp, Pe, EB, SjS, sLE, sSc, study design, age, gender, follow-up period (≥ 12 months), implant survival rate. Implant-related weighed mean values of implant survival rate (wmSR) were calculated. Results After a mean follow-up period (mfp) of 44.6 months, a wmSR of 98.3 % was calculated from data published for patients with oLp (100 patients with 302 implants). Data of 27 patients (152 implants) with EB revealed wmSR of 98.7 % following mfp of 32.6 months. For 71 patients (272 implants) with SjS, wmSR was 94.2 % following a mfp of 45.2 months, and for 6 patients (44 implants) with sSc, wmSR was 97.7 % after mfp of 37.5 months. One case report on one patient each with Pe (two implants) as well as sLE (6 implants) showed 100 % SR following at least 24 months. Conclusions Guidelines regarding implant treatment of patients with oLp, Pe, EB, SjS, sLE or sSc do not exist nor are contraindicating conditions defined. Implant survival rates of patients affected are comparable to those of healthy patients. For implant-prosthetic rehabilitation of patients with Pe and sLE no conclusions can be drawn due to lack of sufficient clinical data. Implant-prosthetic treatment guidelines regarding healthy patients should be strictly followed, but frequent recall is recommended in patients affected with oLp, SjS, EB, SSc, Pe or sLE. Key words: Dental implants, implant supported prosthesis, oral lichen planus, Sjögren´s syndrome, epidermolysis bullosa, systemic sclerosis, pemphigus, systemic lupus erythematosus.