Biomedical subjects

L P Samaranayake

Publications and source records attributed to L P Samaranayake.

At least 91 records · Page 5Linked to original sources

PubMed2000

Antimycotic agents in oral candidosis: an overview: 1. Clinical variants.

The advent of the human immunodeficiency virus and the increasing prevalence of immunocompromised individuals in the community have resulted in a resurgence of opportunistic infections, including oral candidoses. Despite the availability of a number of effective antimycotics for the management of oral candidoses, therapeutic failure is not uncommon. Further, the presence of many clinical variants of oral candidosis, both new and old, may confound the unwary clinician and complicate its management. These problems have been partly circumvented by the introduction of the triazole group of antimycotics, which initially appeared to be highly effective. However, an alarming increase in organisms resistant to triazoles has been reported recently. In this paper we provide an overview of clinical variants of oral candidosis. A second paper will discuss recent advances in the usage of antimycotics in the management of this condition.

AIDS-Related Opportunistic Infections↗

PubMed2000

Antimycotic agents in oral candidosis: an overview: 2. Treatment of oral candidosis.

As both humans and fungi are eukaryotic organisms, antifungal agents affect their cellular metabolism. Thus, a relatively few antifungals with minimal toxicity and side-effects are available compared with a plethora of antibacterials. These agents currently prescribed in dentistry belong to two major groups, the polyenes (nystatin and amphotericin B) and the azoles (imidazoles and triazoles). A newly recognized phenomenon known as the post-antifungal effect implies that antifungals, even at sub-therapeutic concentrations, may suppress the virulent attributes of yeasts, especially intra-orally where topical drug levels fluctuate dramatically during dosing intervals.

Amphotericin B↗

PubMed2000

Growth of the fungal pathogen Candida in parotid saliva of patients with burning mouth syndrome.

Subclinical Candida infection has been suggested as one of the aetiological factors in patients with burning mouth syndrome (BMS). In order to investigate the possible factors which contribute to the relatively high isolation rate of Candida in BMS, parotid saliva samples (20 in toto) from patients with this condition were collected and the growth of Candida in each sample dynamically observed using a computerized turbidometric assay system. A total of thirteen parotid saliva samples obtained from healthy individuals served as normal controls. The results showed no significant growth differential within the test and control saliva samples, when a single isolate each of Candida albicans and Candida tropicalis were cultured for 24 h, at 37 degrees C. A single isolate of Candida glabrata tended to grow better in the saliva from BMS patients than the controls. These results indicate that the composition of saliva may be a contributory factor for the high isolation rate of Candida in saliva of BMS patients.

Adult↗

PubMed2000

Oral health status, oral microflora, and non-surgical periodontal treatment of renal transplant patients receiving cyclosporin A and FK506.

OBJECTIVES: To determine the oral health status, oral microflora and the effect of non-surgical periodontal treatment on gingival overgrowth of renal allograft recipients receiving either cyclosporin A (CsA) or FK506 (Tacrolimus) as an immunosuppressant. MATERIALS AND METHODS: A total of 47 patients receiving CsA (mean age 43.1 years) and 10 receiving FK506 (mean age 40.1 years) were included in the study. Stone casts were taken for measurement of gingival overgrowth. An oral rinse technique was used to investigate the prevalence of yeasts, and aerobic and facultatively anaerobic Gram-negative rods (AGNR). RESULTS: The CsA and FK506 patients exhibited a Gingival Overgrowth Index (GOI) of 45.2%, and 25.1%, respectively (p < 0.05). The CsA patients had a GOI of 15.2% after one year of non-surgical periodontal treatment. The difference between pre- and postoperative gingival overgrowth indices was significant (p < 0.0001). Candida albicans and Klebsiella pneumoniae were the most notable yeast and AGRN found. CONCLUSIONS: Renal transplant patients, being immunocompromised, constitute a high-risk group for gingival overgrowth. However, the FK506 regime appeared to ameliorate this effect, compared with CsA. Non-surgical periodontal treatment was effective in reducing established gingival overgrowth in both CsA and FK506 patients (p < 0.05). Adequate pre- and post-transplant oral health care is recommended, for these patients, irrespective of the drug regime.

Adult↗

PubMed1999

Up-regulation of Fas ligand and down-regulation of Fas expression in oral carcinogenesis.

An important molecule involved in delivering the death signal that initiates apoptosis is called Fas, or Apo-1, which sits on the cell surface. When another molecule called the Fas ligand (FasL) binds to it, Fas triggers a series of events inside the cell that leads to apoptosis. In order to investigate the mechanism of immune escape and the expression of Fas and FasL in oral premalignant lesions (OPLs) and oral squamous cell carcinomas (OSCCs), a total of 64 samples were evaluated by an immunohistochemical method using a labelled streptavidin-biotin assay. These samples comprised nine hyperkeratotic and 24 oral premalignant lesions (nine of mild, moderate, and six of severe dysplastic lesions), and 24 OSCCs, together with seven healthy controls. The results demonstrated that the majority of invasive OSCCs showed down-regulation of Fas expression but up-regulation of FasL expression. These phenomena were also detected in OPLs. The results indicate that the expression of Fas and FasL is involved in oral carcinogenesis and this may be a mechanism by which the cancer cells evade the host immune assault. Perhaps, in future, Fas/FasL system may be used as a prognostic biomarker in predicting the behavior of oral premalignant lesions.

Apoptosis↗

PubMed1999

Adhesion of oral Candida species to human buccal epithelial cells following brief exposure to nystatin.

Opportunistic oral infections caused by Candida albicans and non-albicans Candida species are particularly common in compromised patients. Nystatin, which belongs to the polyene group of antimycotics, is frequently used as a topical agent in the treatment of oro-pharyngeal candidosis. It is recognized that due to the delivery mode of nystatin (i.e. topical, intermittent), as well as the cleansing effect of saliva within the oral environment, the yeasts undergo a relatively brief exposure to this drug during treatment. Nevertheless, there is a sparsity of data on the effect of such brief exposure to nystatin on the pathogenic attributes of Candida such as their adherence to host surfaces. The adhesion of microbes to host mucosal surfaces is a major determinant of successful colonization and infection. Thus the main aim of our investigation was to compare the in vitro adhesion of 30 oral isolates of Candida belonging to six different species (comprising Candida albicans, Candida tropicalis, Candida glabrata, Candida guilliermondii, Candida krusei and Candida parapsilosis) to human buccal epithelial cells, following their brief exposure (1 h) to minimum inhibitory concentration of nystatin, and subsequent removal of the drug. The adhesion of these isolates to buccal epithelial cells was assessed by a previously described adhesion assay. Compared with the controls, there was a significant reduction in buccal epithelial cell adhesion of all six Candida species after drug exposure (54%-68%). However the adhesion of C. albicans isolates was the least affected by nystatin exposure, which was significantly different from that of the non-albicans species. These findings imply that sub-therapeutic levels of nystatin, which are likely to persist in the oral cavity during dosing intervals, may also be beneficial, as they inhibit candidal colonization. The significant difference in nystatin-induced suppression of adhesion between C. albicans and the non-albicans species investigated is a further testimonial for the pre-eminent virulence of the former species.

Antifungal Agents↗

PubMed1999

Granulocyte elastase activity and PGE2 levels in gingival crevicular fluid in relation to the presence of subgingival periodontopathogens in subjects with untreated adult periodontitis.

This study aimed to determine the association between the levels of granulocyte elastase and prostaglandin E2 (PGE2) in GCE and the concomitant presence of periodontopathogens in untreated adult periodontitis (AP). GCF and subgingival plaque were sampled by paper strips and paper points respectively, from various periodontal sites in 16 AP subjects. Granulocyte elastase activity in GCF was analyzed with a low molecular weight substrate specific for granulocyte elastase, pGluProVal-pNA, and the maximal rate of elastase activity (MR-EA, mAbs/min/site) was calculated. PGE2 levels in GCF were determined by radioimmunoassay. 5 species-specific DNA probes were used to detect the presence of A. actinomyceterncomitans (A.a., ATCC 43718), B. forsythus (B.f, ATCC 43037), P. gingivalis (P.g., ATCC 33277), P. intermedia (P.i., ATCC 33563), and T. denticola (T.d., ATCC 35405), with a sensitivity of 10(3) cells/paper point. No A.a. was detectable from all sites sampled. The predominant combination of species detected was B.f., P.g., P.i. & T.d. and it was significantly higher at periodontitis sites (68%) than at healthy (7%) or gingivitis sites (29%) (p<0.05). Overall, MR-EA values were strongly correlated with PGE2 levels (r=0.655, p<0.001), especially at these periodontitis sites co-infected by B.f., P.g., P.i. & T.d. (r=0.722, p<0.001). The periodontitis sites co-infected by the 4 species were observable from 15 subjects. These sites were sub-grouped into 8 subjects with a high MR-EA and 7 subjects with a low MR-EA. The PGE2 levels in the high MR-EA group were significantly higher than in the low MR-EA group (p<0.05). No significant differences in clinical or bacterial data were found between the two groups. While within the high MR-EA group, similar results were found between the paired periodontitis sites in each subject with highest and lowest MR-EA values. This study shows that the local host response to bacterial challenge in untreated periodontal pockets is diverse in terms of the intensity of inflammatory response measured by granulocyte elastase and PGE2 levels in GCE A more thorough evaluation of the risk for active periodontal disease may involve the combined approaches to the test of the dynamic bacteria-host relations.

Adult↗

PubMed1999

Factors affecting the adherence of Candida albicans to human buccal epithelial cells in human immunodeficiency virus infection.

Adherence to host surfaces is an essential prerequisite for colonization and infection. We compared the adherence of 15 oral isolates of Candida albicans harvested from human immunodeficiency virus (HIV)-infected individuals and 12 isolates from HIV-free individuals to buccal epithelial cells (BECs) from HIV-free individuals, and the adherence of a reference strain of C. albicans to BECs from HIV-infected as well as HIV-free individuals. C. albicans from HIV-infected individuals showed adherence values similar to those from HIV-free individuals. The clinical and laboratory parameters of the subjects from whom the Candida were isolated did not correlate with adherence. A reference strain of C. albicans (GDH 1957), however, adhered more readily to BECs from HIV-infected individuals than to cells from an HIV-free cohort. Several variables were found to be associated with the adherence of C. albicans to BECs from HIV-infected individuals: use of zidovudine, antibacterials and antiparasitics was associated with increased adhesion, while haemophilia, heterosexuality, bisexuality, increased age, decreased CD4 + count and use of folate were associated with a decreased candidal adhesion (all P < 0.05). Our data suggest that the quality of BECs including their receptivity to Candida may play an important part in increasing the oral yeast carriage in HIV infection.

AIDS-Related Opportunistic Infections↗

PubMed1999

In vitro susceptibility of Candida species to lactoferrin.

Lactoferrin is an antimicrobial protein present in human mucosal secretions as well as saliva. As there is no information on the relative fungicidal activity of human and bovine lactoferrin, an oral isolate of Candida albicans was studied for its susceptibility to these two proteins. Exposure to a concentration of 20 micrograms ml-1 of either HLF or BLF at 37 degrees C inactivated the yeast to the same degree irrespective of the incubation time of 45, 90 or 150 min. A similar study, using 20 micrograms ml-1 BLF and an incubation time of 150 min, elicited varying anticandidal activity against 35 isolates belonging to six different Candida species. Thus, BLF was fungicidal for the six Candida species in the following decreasing order, C. tropicalis > C. krusei > C. albicans > C. guilliermondii > C. parapsilosis > C. glabrata; the latter being the most resistant. These Candida species also demonstrated significant intra-species variation in susceptibility to the protein (P < 0.05). When the yeast cells exposed to BLF were examined by cryo-scanning electron microscopy, profound cell wall changes such as cell surface blebs, swelling and cell collapse were noted. These findings suggest that lactoferrin, a constituent of saliva, may differentially modulate the carriage of Candida species in the oral cavity.

Animals↗

PubMed1999

Effects of modified pellicles on Candida biofilm formation on acrylic surfaces.

The role of saliva or serum proteins, such as mucin, fibronectin (FN) and mannan-binding protein, on Candida biofilm formation was investigated. Supplementation of saliva with FN had no significant effect on biofilm formation. In contrast, biofilm formation on either mucin-coated or FN-coated acrylic surfaces was significantly less than that of the control. These results suggest that salivary mucin or FN alone does not facilitate biofilm formation of Candida. Supplementation of serum with FN increased biofilm formation of C. glabrata compared with the control. Pretreatment of serum with anti-FN monoclonal antibody significantly reduced biofilm formation, as did pretreatment of serum with anti-mannan-binding protein monoclonal antibody or Con-A. Therefore, Candida biofilm formation on acrylic surfaces appears to be a complex phenomenon involving a multiplicity of proteins operating intraorally.

Acrylates↗

PubMed1999

A new, semi-automated technique for quantification of Candida adherence to denture acrylic surfaces.

Adherence of Candida species to various host surfaces is an important prerequisite for colonization and pathogenesis. Researchers have problems in quantifying candidal adherence to plastic surfaces (used for fabrication of prostheses) due to coaggregation of adherent yeasts and to the laborious, time-consuming method of microscopic quantification. We describe here, a semi-automated image analysis system which is superior to conventional visual light microscopic techniques of quantifying yeasts attached to solid substrates such as acrylic. The results demonstrated a significant positive correlation between the number of cells quantified by traditional light microscopy and the corresponding area obtained by the semi-automated image analysis system (r = 0.83, P < 0.02). The new system is simple, less laborious and is particularly useful when the adherent attributes of a large battery of yeasts are characterized.

Acrylic Resins↗

PubMed1999

The expression of secreted aspartyl proteinases of Candida species in human whole saliva.

The expression of secreted aspartyl proteinases (Saps) by clinical isolates of Candida albicans, C. tropicalis and C. parapsilosis in human saliva supplemented with glucose and in a proteinase-inducing medium (YCB-BSA), was investigated. Also, yeast growth, pH fluctuation and total protein concentration of the saliva cultures during incubation were measured. Sap expression was assessed by evaluating the enzyme activity as well as the antigen concentration. Saps were expressed well in human saliva supplemented with glucose by all three Candida species, although greater expressions was found in YCB-BSA medium. C. albicans isolates were significantly more proteolytic than the non-albicans isolates. In general, for all three species, the rate of yeast growth, pH fluctuation and percentage reduction of total salivary protein concentration concurred with the degree of expression of Saps. These data strongly suggest that Saps of C. albicans, C. tropicalis and C. parapsilosis may play an active role in the progression of oral candidoses, particularly with regard to the abundance of low pH microenvironments in the oral cavity, which are regularly replenished with dietary carbohydrates.

Animals↗

PubMed1999

Inhibition of growth and secreted aspartyl proteinase production in Candida albicans by lysozyme.

Lysozyme (muramidase) is a non-specific, antimicrobial protein ubiquitous in human mucosal secretions such as saliva. Although its antibacterial and antifungal activities are well recognised, there are no data on the specific concentrations necessary to affect the growth of Candida albicans or about the effect of lysozyme on the production of secreted aspartyl proteinase (Sap), a putative virulence factor of C. albicans. Five Sap-producing isolates of C. albicans were cultured in YCB-BSA medium with various concentrations of lysozyme to examine its effect on yeast cell growth, ultrastructural cellular topography and extracellular and intracellular Sap concentration and activity. Lysozyme was candidacidal at high concentrations and decreased significantly the extracellular Sap concentration at sublethal doses, accompanied by intracellular accumulation of the enzyme. At low concentrations of lysozyme (c. 10 microg/ml), Sap activity decreased more than two-fold and Sap concentration decreased five-fold without any appreciable effect on cell growth or viability. Ultrastructural investigations showed ballooned cells and cells with invaginations (especially present near bud scars), indicating that cell-wall components may be possible targets for this enzyme. All concentrations of lysozyme tested were well within physiologically attainable levels. These data suggest that lysozyme has, at least, a bimodal action on C. albicans, killing the organism at higher concentrations and modulating Sap metabolism at lower concentrations.

Anti-Infective Agents↗

PubMed1999

The in vitro post-antifungal effect of nystatin on Candida species of oral origin.

The post-antifungal effect (PAFE) is defined as the suppression of growth that persists following limited exposure of yeasts to antimycotics and subsequent removal of the drug. Although limited data are available on the PAFE of nystatin on oral isolates of C albicans, there is no information on non-albicans Candida species. As nystatin is the commonest antifungal agent prescribed in dentistry, the main aim of this investigation was to measure the PAFE of oral isolates of Candida belonging to six different species (five isolates each of C. albicans, C. tropicalis, C. krusei, C. parapsilosis, C. glabrata and C. guilliermondii) following limited exposure (1 h) to nystatin. The yeasts were examined for the presence of the PAFE after 1 h exposure to the minimum inhibitory concentration (MIC) of nystatin. The PAFE was determined as the difference in time (h) required for the growth of the drug-free control and the drug-exposed test cultures to increase to the 0.05 absorbance level following removal of the antifungal agent. The mean duration of nystatin-elicited PAFE was lowest for C. albicans (6.85 h) and greatest for C. parapsilosis (15.17 h), while C. krusei (11.58 h), C. tropicalis (12.73 h), C. glabrata (8.51 h), and C. guilliermondii (8.68 h) elicited intermediate values. These findings clarify another intriguing possibility for the persistent, chronic recurrence of oral C. albicans infections despite apparently adequate antifungal drug regimens. The significant variations in nystatin-induced PAFE amongst non-albicans species may also have clinical implications, in terms of nystatin regimens used in the management of these fungal infections.

Analysis of Variance↗

PubMed1999

Oral manifestations of HIV infection in a group of predominantly ethnic Chinese.

A total of 32 HIV-infected, predominantly ethnic Chinese individuals from Hong Kong were examined for oral mucosal lesions over a period of 1 year. The commonest oral lesion found was minor aphthous ulceration (27.4%), while xerostomia (17.8%), ulceration NOS (not otherwise specified; 12.3%), hairy leukoplakia (11.0%) and erythematous candidiasis (6.9%) were less frequent; Kaposi's sarcoma was notable for its absence. When the relationship between the number of oral lesions with age, risk group, medication taken, CDC staging and CD4+ count of the study group was investigated, a significantly higher number of oral lesions was associated with use of AZT, homosexuals and CDC stage IV; in contrast, a smaller number of lesions was found in those on antiparasitics and multivitamins (all P<0.05). When compared with studies from other parts of the world, the frequency of oral lesions appeared to be less common in the current study group. However, due to a lack of similar studies from the Asian region, especially in ethnic Chinese, it is not clear whether this difference could be attributed to racial, social or geographic factors.

Adult↗

PubMed1999

Expression of p16 and CDK4 in oral premalignant lesions and oral squamous cell carcinomas: a semi-quantitative immunohistochemical study.

The protein, p16, the product of cyclin-dependent kinase number 2 (CDKN2) gene, is one of the negative regulators of the cell cycle. CDK4, encoded by CDK4 gene, is the substrate of p16. We investigated the expression of p16 and CDK4 and their role in the progression of oral premalignant lesions (OPLs) and oral squamous cell carcinomas (OSCCs) in a Chinese cohort. A total of 74 samples were obtained from patients with hyperkeratosis (10), OPLs [30; mild (10), moderate (10) and severe (10) dysplastic lesions], OSCCs (15; 8 non-metastatic, 7 metastatic), and normal oral tissues (10), together with local lymph nodes (9) of patients with metastatic OSCCs. A labelled streptavidin biotin (LSAB) immunohistochemistry assay was performed and a semi-quantitative method was used to evaluate the staining intensity. The staining patterns of p16 and CDK4 were similar in all tissues and were located in both the nuclei and the cytoplasm. However, the antigen distribution characteristics and the degree of expression of both p16 and CDK4 varied at different developmental stages of the lesions. Hyperkeratotic and dysplastic lesions tended to display a progressively increasing degree of p16- and CDK4-positive nuclei as compared with normal tissues. Also, positive staining cytoplasm was highly evident in OSCCs with a very low nuclear staining (P<0.05). Forty-six of 56-, p16-positive cases were CDK4-positive, while only 6 were CDK4-positive but p16-negative, implying a high correlation between these parameters (r=0.813, P<0.001). This study indicates that the expression of p16 and CDK4 is intimately involved in the development of OPLs and OSCCs and the likely existence of a positive feedback loop between p16 and CDK4.

Adult↗

PubMed1999

The relationship between the acid and alkaline phosphatase activity and the adherence of clinical isolates of Candida parapsilosis to human buccal epithelial cells.

Candida parapsilosis is an emerging fungal pathogen implicated in many diseases, especially in compromised hosts. Candidal colonization and infection depends on the initial ability to adhere to host surfaces, which in turn depends upon the cell wall components and the allied structures of both the host and the fungus. Examination of a miscellaneous collection of 24 C. parapsilosis isolates, from both superficial and deep infections, for their potential pathogenic traits displayed a relationship between the phosphatase activity measured with p-nitrophenol phosphate and adhesion of the yeasts to human buccal epithelial cells (BECs). Significant intraspecies differences were seen in both the alkaline and acid phosphatase activity as well as in their adhesion to BECs (p<0.0001). The acid phosphatase activity of the superficial isolates was significantly greater (152%) than that of the systemic isolates (p = 0.0352). A highly significant positive correlation was also established between the yeast adhesion to BECs and both the acid (r = 0.88, p<0.0001) and alkaline (r = 0.9, p<0.0001) phosphatase activity. These relationships, described here for the first time, imply that phosphatases of Candida species may play a crucial role in potentiating their virulence.

Acid Phosphatase↗

PubMed1999

Oral health and microflora in an institutionalised elderly population in Canada.

A cross-sectional study was undertaken to assess the oral health of a group of elderly, long-term care, institutionalised residents in a facility in Edmonton, Canada. In addition, the oral occurrence of Candida and coliform micro-organisms was evaluated to examine the relationship between oral health status and oral prevalence of these opportunistic pathogens. The mean age of 63 examined individuals was 83.4 (+/- 17.6) years; 28.6 per cent were dentate with a DMF score of 22.4; 4.5 per cent of teeth exhibited root caries. Of the edentate, 55.5 per cent were wearing complete maxillary and mandibular dentures; 59 per cent of the maxillary dentures and 20 per cent of mandibular dentures were found to exhibit good retention and stability while the remaining prostheses were deemed to be poor; 17 per cent of individuals had neither teeth or dentures. Denture stomatitis was the most common mucosal lesion and was found amongst one third of the denture wearers. Three quarters of the residents harboured oral yeasts, 30 per cent coliforms and a significant number exhibited poor oral hygiene and oral pathoses for which remedial treatment was readily available in the form of subsidised dental care.

Aged↗