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RU Radboud Universiteit Nijmegen, 30 juni 2008, Promotor : Jansen, J.A. Co-promotor : Mikx, F.H.M., Contains fulltext : 71501.pdf (publisher's version ) (Open Access), We investigated: a) relationships between molecular properties and antimicrobial functions of MUC7 peptides, b) effects of host physiological factors on the antimicrobial activity of MUC7 peptides, c) enhancement of antifungal activity by combination of MUC7 peptides with EDTA or other agents, d) antibacterial activity of MUC7 peptides against dental biofilm and e) toxicity of the MUC7 peptides. In conclusion: MUC7 12-mer peptide is a potential candidate for the development of a novel antifungal therapeutic agent. This peptide is not sensitive to mono- or divalent cations except for calcium ions at oral physiological-like concentrations. The peptide is thermo-stable and possesses a broad optimal pH value that ranges from neutral to slightly alkaline. MUC7 12-mer is less susceptible to degradation by salivary proteases derived from oral bacteria, compared to other CAMPs. MUC7 12-mer with D-amino acid substitution is resistant to proteolysis while also retaining an effective antifungal activity. Protease inhibitors cocktails and EDTA enhance the activity of MUC7 12-mer. The combination MUC7 12-mer with histatin5 12-mer or MUC7 12-mer with miconazole could potentially enhance the efficacy of antifungal therapy. MUC7 peptides have preferential antibacterial activity against S. mutans and may potentially be used as promising selective anti-dental plaque agents for the prevention of a cariogenic biofilm. MUC7 peptides are not toxic to mammalian cells under normal physiological conditions. The findings presented in the thesis strongly suggest that MUC7 12-mer peptide could potentially be used as a promising agent for the development of novel drugs that control oral microbial infection. The therapeutic efficacy may potentially be enhanced by the use of MUC7 12-mer D-enantiomers as well as the combinations of MUC7 12-mer and EDTA or other antimicrobial agents.

Contains fulltext : 70964.pdf (publisher's version ) (Open Access), BACKGROUND: In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis. METHODS: A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients with oropharyngeal candidiasis at the Muhimbili National Hospital, Dar es Salaam, Tanzania. Identification of the yeasts was performed using standard phenotypic methods. Antifungal susceptibility to fluconazole, itraconazole, miconazole, clotrimazole, amphotericin B and nystatin was assessed using a broth microdilution format according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI; M27-A2). RESULTS: Candida albicans was the most frequently isolated species from 250 (84.5%) patients followed by C. glabrata from 20 (6.8%) patients, and C. krusei from 10 (3.4%) patients. There was no observed significant difference in species distribution between patients with primary and recurrent oropharyngeal candidiasis, but isolates cultured from patients previously treated were significantly less susceptible to the azole compounds compared to those cultured from antifungal naive patients. CONCLUSION: C. albicans was the most frequently isolated species from patients with oropharyngeal candidiasis. Oral yeast isolates from Tanzania had high level susceptibility to the antifungal agents tested. Recurrent oropharyngeal candidiasis and previous antifungal therapy significantly correlated with reduced susceptibility to azoles antifungal agents.

Contains fulltext : 70991.pdf (publisher's version ) (Open Access), BACKGROUND: Oropharyngeal candidiasis is the most common opportunistic infection affecting patients with human immunodeficiency virus (HIV) infection. Because of convenience, cost, and reluctance to complicate antiretroviral treatment regimens, single-dose fluconazole may be a favorable regimen for treatment of moderate to severe oropharyngeal candidiasis. We conducted a prospective, randomized, double-blind, placebo-controlled trial to compare the clinical and mycological responses, relapse rates, and safety of a single 750-mg dose and a 14-day course of treatment with fluconazole. METHODS: A total of 220 HIV-infected patients with clinical and mycological evidence of oropharyngeal candidiasis were randomly assigned in a 1:1 ratio to receive either a 750-mg single dose of orally administered fluconazole (110 patients) or 150 mg of orally administered fluconazole once per day for 2 weeks (110 patients). The primary efficacy analysis was based on clinical and mycological responses at the end of treatment. Secondary parameters were safety and relapse rate. RESULTS: Single-dose fluconazole was equivalent to a 14-day course of fluconazole in achieving clinical and mycological cure, with clinical cure rates of 94.5% and 95.5%, respectively (odds ratio, 0.825; 95% confidence interval, 0.244-2.789; P= .99), and mycological cure rates of 84.5% and 75.5%, respectively (odds ratio, 1.780; 95% confidence interval, 0.906-3.496; P= .129). Drug-related adverse events were uncommon and were not different between the treatment groups. CONCLUSION: A single dose of 750 mg of fluconazole was safe, well tolerated, and as effective as the standard 14-day fluconazole therapy in patients with HIV infection and acquired immunodeficiency syndrome who had oropharyngeal candidiasis coinfection.

Contains fulltext : 51241.pdf ( ) (Open Access), BACKGROUND: The aim of the study was to compare the prevalence and types of HIV-related oral lesions between children and adult Tanzanian patients on HAART with those not on HAART and to relate the occurrence of the lesions with anti-HIV drug regimen, clinical stage of HIV disease and CD4+ cell count. METHODS: Participants were 532 HIV infected patients, 51 children and 481 adults, 165 males and 367 females. Children were aged 2-17 years and adults 18 and 67 years. Participants were recruited consecutively at the Muhimbili National Hospital (MNH) HIV clinic from October 2004 to September 2005. Investigations included; interviews, physical examinations, HIV testing and enumeration of CD4+ T cells. RESULTS: A total of 237 HIV-associated oral lesions were observed in 210 (39.5%) patients. Oral candidiasis was the commonest (23.5%), followed by mucosal hyperpigmentation (4.7%). There was a significant difference in the occurrence of oral candidiasis (chi2 = 4.31; df = 1; p = 0.03) and parotid enlargement (chi2 = 36.5; df = 1; p = 0.04) between children and adults. Adult patients who were on HAART had a significantly lower risk of; oral lesions (OR = 0.32; 95% CI = 0.22 - 0.47; p = 0.005), oral candidiasis (OR = 0.28; 95% CI = 0.18 - 0.44; p = 0.003) and oral hairy leukoplakia (OR = 0.18; 95% CI = 0.04 - 0.85; p = 0.03). There was no significant reduction in occurrence of oral lesions in children on HAART (OR = 0.35; 95% CI = 0.11-1.14; p = 0.15). There was also a significant association between the presence of oral lesions and CD4+ cell count < 200 cell/mm3 (chi2 = 52.4; df = 2; p = 0.006) and with WHO clinical stage (chi2 = 121; df = 3; p = 0.008). Oral lesions were also associated with tobacco smoking (chi2 = 8.17; df = 2; p = 0.04). CONCLUSION: Adult patients receiving HAART had a significantly lower prevalence of oral lesions, particularly oral candidiasis and oral hairy leukoplakia. There was no significant change in occurrence of oral lesions in children

Contains fulltext : 50678.pdf (publisher's version ) (Closed access), Using the ethnobotanical approach, some Tanzanian plants reported to be used by traditional healers for the treatment of oral candidiasis and fungal infections of the skin were collected and screened for their antifungal activity against Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei and Cryptococcus neoformans. A total of 65 crude methanol extracts belonging to 56 plant species and 38 families were screened using the broth microdilution method, according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI) (formerly, National Committee for Clinical and Laboratory Standards) [National Committee for Clinical Laboratory Standards, 2002. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Approved Standard-2nd Edition M27-A2, National Committee for Clinical Laboratory Standards, Wayne, PA, USA]. Among the tested plant species, 45% (25 species) showed antifungal activity against one or more of the test fungi. The most susceptible yeasts were Cryptococcus neoformans, followed by Candida krusei, Candida tropicalis, and Candida parapsilosis. The least susceptible were Candida albicans and Candida glabrata. Strong antifungal activity was exhibited by extracts of Clausena anisata Oliv., Sclerocariya birrea Sond, Turraea holstii Gurk, Sterculia africana (Lour) Fiori, Acacia robusta subsp. Usambarensis (Taub) Brenan, Cyphosterma hildebrandti (Gilg), Desc, Elaeodendron buchannanii (Lows), Acacia nilotica (L.) Wild ex Del, Jatropha multifida L., and Pteridium aquilinum (L.) Kuhn.

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Contains fulltext : 22170___.PDF (publisher's version ) (Open Access)

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KUN, Promotores : König, K.G.G., Maltha, J.C., Mikx, F.H.M., Item does not contain fulltext