Autoimmune hepatitis and autoimmune manifestations in patients with chronic viral hepatitis

Mucosal adherence and germ tube formation have been considered as important virulence factors of Candida albicans. We investigated 11 clinical isolates (among them six isolates from oesophageal thrush) for quantification of adherence to buccal epithelial cells and germ tube formation in the continuous flow culture in vitro, and correlated the results with the clinical data of the patients. Adherence varied considerably between the different C. albicans strains. Strains recovered from clinically, culturally and serologically confirmed oesophageal thrush adhered stronger to buccal epithelial cells. Isolates from cases with heavy colonisation but clinically without candidosis were less adherent. Only after 30 min germ tube formation was observed in the continuous flow culture. Strains with stronger adherence also showed significantly faster and increased germ tube formation. The patients with oesophageal thrush did not suffer any particular immunosuppression such as HIV infection, although in most cases chronic alcoholism was apparent. We conclude, that in cases with minor immunosuppression the expression of the virulence factors adherence and germ tube formation plays an important role in the pathogenesis of candidosis, whereas it may be of less importance in cases with severe immunosuppression. In the latter they may, however, influence outcome.     

Identification of hashish samples with inductively coupled high-frequency plasma emission spectrometry and neutron activation analysis and data handling with neuronal networks. 1. Methods for the quantitative determination of characteristic trace elements]

The adherence of six clinical Candida albicans isolates to buccal epithelial cells obtained from AIDS patients, solid organ transplant recipients and healthy individuals was compared. It was shown that Candida albicans bound in significantly greater numbers to epithelial cells obtained from AIDS patients than to those from healthy individuals or transplant patients, and that the adherence capacity varied among the strains tested.     

Improved determination of urinary cortisol and cortisone, or corticosterone and 11-dehydrocorticosterone by high-performance liquid chromatography with ultraviolet absorbance detection

This study investigated the effect of the chitin synthetase inhibitors, the nikkomycins (NZ and NZ+NX), on Candida albicans adhesion to buccal epithelial cells (BECs) in vitro. The effect was expressed in reduced chitin synthetase activity and chitin content of fungal cells. In vitro adhesion assays to BECs of Candida exposed to NZ and NZ+NX revealed reduced adhesion values. Light, scanning and transmission electron microscopy (SEM, TEM) of NZ-treated and untreated micro-organisms showed changed fungal morphology and reduced adherence of the treated yeasts. Scanning electron microscopy of NZ-treated C. albicans labelled with gold-conjugated wheatgerm agglutinin (WGA) revealed less labelling than in the untreated organisms. A close contact between the fungus and the epithelial cell at a site with intense WGA-gold labelling was noted in TEM experiments. The data point to the involvement of chitin in the adhesion of C. albicans to epithelial cells.     

Adhesion of oral Candida albicans isolates to denture acrylic following limited exposure to antifungal agents

Candidal adherence to denture acrylic surfaces is implicated as the first step in the pathogenesis of Candida-associated denture stomatitis, the most prevalent form of oral candidosis in the West. This condition is treated by topically administered antifungal agents, mainly belonging to the polyenes and azoles. As the intraoral concentrations of antifungals fluctuate considerably due to the dynamics of the oral environment, the effect of short exposure to sublethal concentrations of antifungals on the adhesion of Candida albicans to denture acrylic surfaces was investigated. Seven oral C. albicans isolates were exposed to four-eight times minimum inhibitory concentrations (MIC) of five antifungal drugs, nystatin, amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole, for 1 h. After removing the drug (by repeated washing) the adhesion of these isolates to acrylic strips was assessed by an in vitro adhesion assay. Exposure to antifungal agents significantly reduced the adherence of all seven C. albicans isolates to denture acrylic. The mean percentage reductions of adhesion after limited exposure to nystatin, amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole were 86.48, 90.85, 66.72, 65.88 and 47.42%, respectively. These findings indicate that subtherapeutic doses of antifungals may modulate oral candidal colonization. Further, these results may have an important bearing on dosage regimens currently employed in treating oral candidosis.     

The impact of contraceptive methods on the onset of symptomatic vulvovaginal candidiasis within the menstrual cycle

OBJECTIVE: Vulvovaginal candidiasis is the second most common cause of vaginal discharge. Low-dose oral contraceptives are no longer thought to increase the absolute risk of episodic vulvovaginal candidiasis. This study investigates the possible impact that hormonal contraception may have on the timing of onset of symptoms within the menstrual cycle. STUDY DESIGN: In a retrospective chart review of reproductive-aged women seen at the Women's Health Care Clinic at Harbor-University of California, Los Angeles, Medical Center, data from the records of 448 symptomatic women who had 507 episodes of vulvovaginal candidiasis were extracted and analyzed for timing of onset of symptoms within the menstrual cycle. Diagnosis was based on symptoms, physical findings, and microscopy. Onset was divided into five physiologic ranges within an idealized 28-day menstrual cycle. Comparisons among groups were made with use of chi 2 and p < 0.05 thresholds for statistical significance. RESULTS: No differences were found in the onset of symptoms within the idealized menstrual cycle ranges between women using hormonal birth control methods and those using nonhormonal ones. The distribution was remarkably uniform throughout the cycle with the exception of the first few days (during menses). CONCLUSION: The timing of onset of symptoms of vulvovaginal candidiasis within a woman's menstrual cycle is not affected by her method of birth control.     

Comparison of four methods of automated recording of physiologic data at one minute intervals

OBJECTIVES: To provide the clinical profile and assess the significance of various risk factors contributing to the occurrence of oral candidosis in newborns. DESIGN: Case-control study. SETTING: Neonatal Intensive Care Unit (NICU). SUBJECTS: Twenty newborns with oral candidosis and an equal number of age and weight matched controls. INTERVENTIONS: All cases of oral candidosis were treated with local application of 1% Clotrimazole. RESULTS: Oral candidosis was documented in 3.2% (20/650) cases in the NICU. Acute pseudomembranous candidosis was the most common presentation. The mean age of onset was 10.5 days. Candida albicans was isolated in 50% cases in addition to C. tropicalis, C. paratropicalis, C. krusei, C. glabrata and C. parapsilosis. On univariate analysis, male sex, birth asphyxia and prolonged antibiotic therapy had a significant correlation with occurence of oral candidosis in neonates. Out of these, birth asphyxia was the only factor significantly associated with oral candidosis (OR 8.09, 95% CI 1.34-48.8, p = 0.0226) on multivariate analysis. CONCLUSIONS: C. albicans was the predominant isolate in this series of oral candidosis. Clinical manifestations were evident in the second week of life and birth asphyxia was the most important associated perinatal event.     

HIV protease inhibitors influence the prevalence of oral candidosis in HIV-infected patients: a 2-year study

The introduction of HIV protease inhibitors was accompanied by reduction in HIV-associated opportunistic infections. Therefore, we performed a retrospective study of HIV-infected patients to evaluate the effects of therapy with an HIV protease inhibitor (PI) on oral candidosis. This was of special interest, because an important virulence factor of Candida albicans is the secreted aspartic protease (SAP), which is assigned to the same class of aspartic proteases as HIV protease. Sixty-two patients were examined five times over a period of 2 years. There was a hint at a difference in the frequencies of C. albicans carrier state and manifest oral candidosis in favour of treatment with a PI. In addition, loss of Candida colonization and manifest oral candidosis was observed only in patients with elevation of CD4 cells upon PI. This might explain the effect, which also might go back to a direct inhibition of yeast SAP.     

Incubation temperatures affect adherence to plastic of Candida albicans by changing the cellular surface hydrophobicity

The influence of cellular surface hydrophobicity on the adherence capacity to plastic of Candida albicans was investigated at two culture temperatures (37 and 22 degrees C). The majority of the 42 strains studied were hydrophobic at 22 degrees C and hydrophilic at 36 degrees C. The hydrophobic cells showed a consistent adherence capacity which was absent from the hydrophilic strains. The culture temperatures affect adherence to plastic of C. albicans by changing the cellular surface hydrophobicity.     

Determination of pseudoephedrine hydrochloride and carbinoxamine maleate in combination drug formulation by liquid chromatography

The permeability to several chemical compounds and the histology of vaginal and buccal mucosa are very similar. Because vaginal mucosa is more abundant, it may be used as a model for the latter. To further develop the vaginal/buccal mucosa model, the objective of the present study was to evaluate the passage of a small polypeptide, vasopressin, across fresh and frozen specimens of these two mucosae. Specimens of fresh buccal and vaginal mucosa were taken from excised tissue obtained following vaginal hysterectomies and various oral surgical procedures. Pieces of buccal and vaginal tissue specimens obtained were used fresh or were snap-frozen and stored at -85 degrees C for periods of up to 10 months. Biopsies from fresh and thawed specimens were mounted in flow-through diffusion cells and their permeability to tritiated vasopressin was determined using a continuous flow-through perfusion system. Specimens were examined histologically before and after freezing as well as before and after permeability experiments and similarities between vaginal and buccal tissues verified. No statistically significant differences between flux values for fresh and frozen vaginal and buccal mucosa, respectively, were found. These results demonstrate that the permeation of vasopressin across fresh and frozen human vaginal and buccal mucosa is for practical purposes similar. These results further support the human vaginal/buccal mucosa model for in vitro permeability studies on therapeutically active compounds.     

Bone marrow capacity for bone cells and trabecular bone turnover in immobilized tibia after sciatic neurectomy in mice

Pseudomonas aeruginosa and Candida albicans were reported to adhere to the glycosphingolipid asialo-GM1 by means of pili and fimbriae, respectively. These diverse adhesins have been previously reported to have an immunologically conserved antigenic epitope and the role of this cross-reactive epitope in adherence to asialo-GM1 was investigated in this study. Both the unbiotinylated PAK pilus and fimbrial adhesins inhibited biotinylated pili from P. aeruginosa PAK and biotinylated C. albicans fimbriae binding to asialo-GM1 and receptors present on human buccal epithelial cells (BECs), which suggested that the same receptor sites were recognized by the two adhesins. Monoclonal antibodies PK99H and Fm16 raised against the P. aeruginosa PAK pili and C. albicans fimbriae, respectively, recognized a conserved epitope present on the two adhesins. Both Fm16 and PK99H blocked fimbriae binding to asialo-GM1 and BEC receptors and also inhibited P. aeruginosa and C. albicans whole cell binding to BECs. These data suggested that the conserved epitope confers receptor-binding properties to the adhesins, demonstrated that (i) asialo-GM1-like receptors present on epithelial cell surfaces are utilized by the pilus and fimbrial adhesins and (ii) the binding to these glycoreceptors is mediated by a conserved epitope that has receptor-binding properties.     

Activity of the renin-angiotensin-aldosterone system in euglycemic type I diabetic patients on intensive insulin treatment without diabetic neuropathy

The yeast Candida albicans coaggregates with a variety of streptococcal species, an interaction that may promote oral colonization by yeast cells. C. albicans and Candida tropicalis are the yeasts most frequently isolated from the human oral cavity and our data demonstrate that both these species bind to Streptococcus gordonii NCTC 7869 while two other Candida species (Candida krusei and Candida kefyr) do not. Adherence of C. albicans was greatest when the yeast had been grown at 30 degrees C to mid-exponential growth phase. For 21 strains of C. albicans there was a positive correlation between the ability to adhere to S. gordonii and adherence to experimental salivary pellicle. Whole saliva either stimulated or slightly inhibited adherence of C. albicans to S. gordonii depending on the streptococcal growth conditions. The results suggest that the major salivary adhesins and coaggregation adhesins of C. albicans are co-expressed.     

Candida albicans morphotypes and in vitro adhesivity to cells of the human oral mucosa in HIV-positive and AIDS patients after exposure of blastospores to fluconazole. II

BACKGROUND: Oro-pharyngeal candidosis is a frequently initial clinical manifestation of HIV infection and the adhesive properties of Candida spp. represent a very important pathogenicity factor. METHODS: In this study the adhesivity rate of Candida albicans to the oral epithelial cells of 33 HIV-positive patients and 12 healthy volunteers, have been assessed before and after the exposure of blastospores to inhibitory concentrations of fluconazole, in relation to 11 morphotypes obtained from 13 C. albicans strains. RESULTS: Results can be summarized as follows: 1) the number of blastospores adhering to the HIV-positive donor' cells is higher than that of blastospores adhering to the healthy donors' cells (rate is 2.7:1); 2) blastospores from strains producing rough or very coarse fringes show adhesive properties higher than those of strains with different morphology; 3) in the group of HIV-positive patients the adhesivity inhibition of blastospores from strains producing rough or very coarse fringes was higher (38.3%) than that of strains with different morphology (33.8%); 4) overall, adhesivity inhibition due to exposure to fluconazole is higher for epithelial cells from healthy donors. CONCLUSIONS: These results can suggest the validity of an antimycotic pretreatment of persons at risk of oro-pharyngeal candidiasis.     

Immunological investigations in vaginal mycoses

In 42 women with chronically recurrent and 20 women with acute Candida albicans vulvovaginitis, as well as 14 women with Candida glabrata vaginitis, the following investigations were carried out: determination of protein content and secretory immunoglobulin A (sIgA) in the cervicovaginal secretion by a self-modified ELISA technique; determination of immunocells and cellbound IgA in the cervicovaginal secretion by immunofluorescence and nephelometric analysis of IgA in the serum. The results were compared with those of 77 pre-menopausal non-pregnant women with or without intake of anti-ovulants, 17 healthy pregnant women and four hysterectomised pre-menopausal women. Due to inflammation, women with acute and chronically recurrent Candida albicans vulvovaginitis had a higher protein content in the cervicovaginal secretion than healthy women. However, the content of secretory IgA was not increased but even slightly decreased in chronic cases. The number of macrophages and granulocytes in the vaginal content was not increased compared with healthy patients. In only a few cases was IgA detected on yeast cells and in the cervicovaginal secretion by fluorescence microscopy. In chronically-relapsing vaginal candidosis, the frequency of the serotype B of C. albicans was strikingly high. Women with Candida glabrata vaginitis showed lower values of secretory sIgA in the vaginal secretion compared with healthy patients as well as women with vaginitis caused by C. albicans. However, like healthy women, they had normal protein values in the cervicovaginal secretion and also lower values of IgA in the serum compared with women of C. albicans vulvovaginitis patients. Macrophages and granulocytes were demonstrable in the cervicovaginal secretion just as in healthy persons. Women with C. glabrata vaginitis showed a more conspicuous, although not a significantly more frequent, binding of IgA to budding cells demonstrated by fluorescence microscopy than women with C. albicans.     

Behavior of rhesus monkeys during artificial menstrual cycles.

Daily sc injections of estradiol, progesterone, and testosterone were given to 17 ovariectomized rhesus monkeys in amounts that imitated accurately the changing plasma levels of hormones in intact females with natural menstrual cycles. Because these cycles in ovariectomized, treated Ss were terminated by normal vaginal bleeding every 28 days and showed a midcycle gonadotropin surge, the authors termed them "artificial menstrual cycles." In dyadic mating tests, changes in the females' access times (leverpressing) for males, and in the males' ejaculatory performance, were closely similar during natural and artificial cycles, and there were well-marked behavioral rhythms. These rhythms were lost during 28-day control periods when ovariectomized Ss received injections of vehicle alone. Differences in ejaculatory performance during natural and artificial cycles could be accounted for by an order effect. It is concluded that the artificial cycle provides a valid and useful paradigm for a more detailed study of the neuroendocrine regulation of primate reproductive behavior. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of limited exposure to antimycotics on the relative cell-surface hydrophobicity and the adhesion of oral Candida albicans to buccal epithelial cells

Candida albicans is the major aetiological agent of oral candidosis. Adhesion to oral mucosal surfaces is considered a prerequisite for its successful colonization and subsequent infection, and its relative cell-surface hydrophobicity (CSH) is a contributory physical force. Thus, the main aim here was to determine the CSH of 10 isolates of oral C. albicans after a short exposure to sublethal concentrations of four antifungal agents and to correlate these findings with their adhesion to human buccal epithelial cells (BEC). The yeasts were exposed to sublethal concentrations of nystatin [x 6 minimal inhibitory concentration (MIC)], 5-fluorocytosine (x 8 MIC), ketoconazole (x 4 MIC) and fluconazole (x 4 MIC) for 1 h. The drug was then removed, and the CSH and BEC adhesion assessed by a biphasic aqueous-hydrocarbon assay and a microscopic method, respectively. The mean percentage reductions of CSH after exposure to nystatin, 5-fluorocytosine, ketoconazole and fluconazole were 27.14% (p = 0.01), 9.46% (p = 0.43), 19.47% (p = 0.04) and 6.16% (p = 0.59). Similarly, exposure to all the drugs except 5-fluorocytosine resulted in a significant inhibition of yeast adhesion to BEC, with nystatin eliciting the highest and fluconazole the least inhibition. Further, on regression analysis a strong positive correlation was observed between CSH and adhesion to BEC after limited exposure to 5-fluorocytosine (r = 0.48, p < 0.0001), ketoconazole (r = 0.48, p < 0.0001), fluconazole (r = 0.55, p < 0.0001) as well as in the unexposed controls (r = 0.41, p = 0.001), although nystatin was an exception (r = 0.09, p = 0.44). Taken together, these data elucidate further mechanisms by which antimycotics may operate in vivo to suppress candidal pathogenicity.     

A new in vitro assay for quantitation of chemotherapy-induced mucositis

Patients receiving high-dose chemotherapy (HD-CT) are at risk of severe mucositis. Most prevention studies evaluate the degree of mucositis on clinical, and therefore subjective, measurements. The aim of this study was to develop an objective in vitro assay of chemotherapy-induced mucositis. Twelve patients with locally advanced breast carcinoma received HD-CT followed by peripheral stem cell reinfusion. Before and twice weekly after HD-CT, the mucosa was evaluated by an oral washing, a buccal smear and the World Health Organization (WHO) toxicity grading; furthermore, blood leucocyte levels were determined. For the oral washings, the percentage of viable epithelial cells was determined by trypan blue dye exclusion and leucocytes were counted by fluorescence microscopy after incubation with acridine orange. Maturity of buccal cells was assessed by staining buccal smears for morphology according to Papanicolaou (Whitacker D and Williams V, 1994). Eight healthy volunteers served as controls. The mean percentage (+/- s.e.m.) of viable oral epithelial cells was stable in controls (44 +/- 2%). In patients, they increased after HD-CT, which was significant after day 7 compared with pretreatment (P < or = 0.05). In addition, a shift from mature to immature epithelial cells in buccal smears was observed. Oral leucocyte levels were closely correlated with the blood leucocyte counts. The WHO score followed the results of these other evaluations with some delay. The viability of buccal cells obtained by oral washings increases after HD-CT. This is possibly because of desquamation of the upper oral mucosa layer, with a shift from mature to more immature cells. These data can be quantitated, and this assay may therefore be useful in studies aimed at prevention of mucositis.     

Effect of Staphylococcal proteinase on adherence of Candida albicans to mucous membrane cells in vitro

The study was aimed at evaluation of influence of staphylococcal proteinase on adherence of Candida albicans to the cheek mucous membrane cells. Epithelial cells were preincubated with the enzyme which was followed by adherence tests. Significant increase of number of cells of Candida albicans adhering to epithelial cells preincubated with enzyme in concentrations of 10 micrograms/ml and 50 micrograms/ml, was detected. Staphylococcal serine protease seems to play an important role in mixed infections caused by fungi and bacteria.     

Prophylaxis of Candida and Aspergillus infections with oral administration of itraconazole

The broad-spectrum oral triazole antifungal, itraconazole, has been shown to be effective in the treatment of superficial and systemic infections with fungi including Candida albicans, C. krusei and C. glabrata, Cryptococcus, Aspergillus, Histoplasma, Blastomyces and others. Its broad spectrum of activity, high and persistent tissue levels and favourable safety profile suggest that it may be appropriate for the prevention of opportunistic fungal infections in at-risk patients. In this study, itraconazole's prophylactic efficacy was tested against experimental models of Candida and Aspergillus infection. A single dose of 1.25 mg kg-1 or 2.5 mg kg-1, given 1 h before vaginal infection with C. albicans, protected 50% of treated rats. In systemic and disseminated candidosis, prophylaxis with itraconazole reduced both folliculitis and organ Candida content in guinea pigs. Amphotericin B was also used in this study and was found to be less efficacious than itraconazole. Itraconazole prolonged survival when administered to guinea pigs before experimental induction of systemic and invasive aspergillosis. In all cases, increasing the itraconazole dosage increased its prophylactic efficacy. Therefore, as the clinical efficacy of itraconazole is accurately reflected by the results of animal models, this study shows itraconazole to be a potential prophylactic therapy for patients at risk of opportunistic fungal infection.     

Adherence of human vaginal lactobacilli to vaginal epithelial cells and interaction with uropathogens

Three strains of Lactobacillus, identified as Lactobacillus acidophilus, Lactobacillus gasseri, and Lactobacillus jensenii, were selected from among 70 isolates from the vaginas of healthy premenopausal women for properties relevant to mucosal colonization or antagonism. All three self-aggregated and adhered to epithelial vaginal cells, displacing well-known vaginal pathogens, such as G. vaginalis, and inhibiting the growth in vitro of Escherichia coli and Streptococcus agalactiae. The surface components involved in self-aggregation appeared to be proteins for L. gasseri and lipoproteins for L. acidophilus and L. jensenii, as judged by susceptibility to treatment with appropriate degrading enzymes. The factors responsible for adherence to epithelial vaginal cells seemed to be glycoproteins (L. acidophilus and L. gasseri) and carbohydrate (L. jensenii). The receptors of the vaginal cells were glycolipids, which presumably were the targets of the competition observed between the lactobacilli and the pathogenic microbes.