Chronic Candidosis Research Articles

Застосування політерапії в місцевому лікуванні хронічного кандидозного стоматиту

Застосування політерапії в місцевому лікуванні хронічного кандидозного стоматиту

Persistent Candida albicans colonization and molecular mechanisms of azole resistance in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients

Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I) suffer from chronic candidosis caused mainly by Candida albicans, and repeated courses of azole antifungals have led to the development of resistance in the APECED patient population in Finland. The aim of our study was to address whether the patients are persistently colonized with the same or genetically closely related strains, whether epidemic strains are present and which molecular mechanisms account for azole resistance. Sets of C. albicans (n = 19) isolates from nine APECED patients reported with decreased susceptibility to fluconazole isolated up to 9 years apart were included. The strains were typed by multilocus sequence typing. CDR1/2, MDR1 and ERG11 mRNA expression was analysed by northern blotting and Cdr1, Cdr2 and Mdr1 protein expression by western blotting, and TAC1 and ERG11 genes were sequenced. All seven patients with multiple C. albicans isolates analysed were persistently colonized with the same or a genetically closely related strain for a mean of 5 years. All patients were colonized with different strains and no epidemic strains were found. The major molecular mechanisms behind the azole resistance were mutations in TAC1 contributing to overexpression of CDR1 and CDR2. Six new TAC1 mutations were found, one of which (N740S) is likely to be a gain-of-function mutation. Most isolates were found to have gained multiple TAC1 and ERG11 point mutations. Despite clinically successful treatment leading to relief of symptoms, colonization by C. albicans strains is persistent within APECED patients. Microevolution and point mutations occur within strains, leading to the development of azole-resistant isolates.

Chronic candidosis and oral cancer in APECED‐patients: Production of carcinogenic acetaldehyde from glucose and ethanol by Candida albicans

According to our results all C. albicans isolates analysed were capable of producing carcinogenic levels of ACH from EtOH. The isolates from cancer and control subjects produced significantly higher amounts of ACH than those from APECED patients but the clinical relevance of this difference is questionable since all isolates produced very high amounts. The 11 mM EtOH concentration used can be found in saliva for hours after social alcohol consumption or naturally in many products produced by fermentation.17The main finding of this study is that C. albicans may play a role in metabolizing glucose to carcinogenic ACH in the mouth and could participate in the pathogenesis of oral cancer in non-alcohol drinkers. The observation supports the concept of a novel microbially mediated mechanism in the pathogenesis of oral cancer and could partly explain why chronic oral candidosis is carcinogenic in APECED patients and why they have a high risk for oral cancer at an early age.

Increase in the Incidence of Allergy to Prosthetic Materials and Local Anesthetics: Immunophysiology and Laboratory Diagnostics of Intolerance

Combined analysis of drug sensitivity in vitro and in vivo is necessary for reliable diagnosis of the intolerance to prosthetic materials and local anesthetics as an intrinsic allergic reaction, especially in the cases of generally weak allergic reactions. Changes in peroxidase release from granulocytes in response to a corresponding substance is an effective in vitro test, and the provocative mucosal-gingival test (MGT) is used in vivo. During the past decade, a growth was observed in the population developing allergies to prosthetic materials and local anesthetics, which is expressed in an increased number of patients with intolerance to these materials against the background of increasing hyperresponsiveness to the drugs which have usually been tolerated well, as well as an increased proportion of patients with a polyvalent allergy to many prosthetic materials and anesthetics. At the same time, the amount of weak responses to drugs in the in vitro test has increased. Some of these patients exhibit a pathologic response to the given drug, which can be detected using the MGT. In most cases, polyvalent allergies to prosthetic materials or anesthetics and a pathological response accompanied by a weak in vitro reaction are found in patients with bronchial asthma and other chronic allergies, chronic candidosis of the oral cavity, and chronic Helicobacter and Giardia lamblia infections.

Comparison of virulence factors of oral Candida dubliniensis and Candida albicans isolates in healthy people and patients with chronic candidosis.

We determined differences in the expression of certain virulence factors between oral Candida dubliniensis and Candida albicans species. In addition, clonal differences were sought among C. albicans isolates recovered from patients with and without compromised immune system. The material comprised 93 clinical yeast isolates originated in 40 subjects (1-5 isolates per subject). All 26 C. dubliniensis isolates and 46 C. albicans isolates originated from healthy routine dental clinic patients. Additionally, 21 C. albicans isolates were collected from patients with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (APECED), who have chronic candidosis as one manifestation of their immunocompromising disease. Polymerase chain reaction amplification using the random sequence primer OPE-03 enabled grouping of the C. dubliniensis isolates in 2 genotypes (I and II) and C. albicans isolates in 15 genotypes (I-XV). No significant difference was found in the distribution of genotypes between the patients with APECED and the healthy subjects. C. dubliniensis isolates exhibited high-frequency phenotypic switching significantly more frequently than did C. albicans isolates, and vice versa regarding phospholipase and proteinase production. Proteinase production was significantly more frequent among C. albicans genotype V than genotype IX isolates. No significant difference was found in expression of virulence factors of C. albicans isolates between the patients with APECED and the healthy subjects.

Therapy of candidosis vulvovaginitis at pregnancy

Clinical effectiveness gyno-pevaryl (GP) is investigated at treatment acute (30 women) and chronic (38 patients) candidosis vulvovaginitis in the period of pregnancy. In an end of course of treatment GP clinical and laboratory the confirmed recovery is marked in the first group at 80.0 % patients, in the second and the third - at 76.3 % patients. Gynopevaryl is an effective preparation for local treatment acute and chronic candidosis vulvovaginitis.

Histopathology, immunology, and serology of oral yeast infections: Diagnosis of oral candidosis

For diagnostic purposes it is normally not important to obtain a biopsy specimen, since an oral smear from the lesion will yield blastospores and pseudohyphae in abundance. However, in lesions that respond poorly to antimycotic treatment a biopsy should be carried out to detect possible malignant changes in the epithelium. Assessment of cell-mediated immunity against Candida albicans and other antigens may be important in patients with severe chronic candidosis to assess the degree of immunocompetence and prognosis. Usually, patients with oral candidosis show only moderately elevated antibody titers in serum and saliva against C. albicans, and serologic tests are normally not a diagnostic tool for oral candidosis. However, such tests may be a prognostic instrument in patients with severe oral candidosis who respond poorly to antimycotic therapy.

Etiology of oral squamous cell carcinoma.

The traditional list of etiological factors related to oral squamous cell carcinoma namely, tobacco, alcohol, syphilis, and oral sepsis has been expanded to include iron deficiency, chronic candidosis, and herpes simplex virus. The development of current concepts in these areas is discussed. In evaluating the need for future research, special emphasis is given to the concepts of multifactorial etiology and the role of mutagens. Suggestions for future research are discussed.

Autoimmune polyendocrinopathy-candidosis syndrome (APECS): Clinical variation, inheritance and HLA association in 40 Finnish patients

At present age of 8-59 years the manifestation was most variable ranging from life-long mild mucocutaneous affection to 4-fold endocrinopathy. The components are of 3 sorts. 1. Ectodermal dystrophy (nails, enamel, hair, cornea, oral mucosa) proved to be independent of endocrinopathy. 2. Cellular immunodefect appeared as chronic candidosis of oral and vaginal mucosa, nails and skin, and anergy to tuberculin and candida. 3. Autoimmune destruction led to hypoparathyroidism (32 patients), Addison's disease (22), female (6/13) and male (2/8) hypogonadism, pernicious anemia (5), diabetes (3) and hypothyroidism (1). No component was constant. Distribution of ancestors' birth places showed an accumulation at 5 rural areas, indicating involvement of a rare gene. Family pattern fitted to autosomal recessive gene (proportion of affected sibs 0.21-0.27 by different methods). Association was significant with HLA A3 (gene frequency 0.53 in contrast to 0.28 in healthy sibs and general population), but not with chromosome 6. The clinical variation appears to be independent of HLA.

Experimental mycosis in immunosuppressed rabbits

Chronic candidosis was established in rabbits by the injection I.V. of 2 X 10(6) cells of C. albicans. The rabbits were assayed every week for 14 weeks for the appearance of candida antigen and anticandida antibodies in serum and other body fluids. Tests were carried out in double diffusion plates; antigen against hyperimmune rabbit sera and antibody against Candida cell sap antigen preparation. A sensitive specific passive hemagglutination procedure was also developed which used chromate treated cells. In rabbits with chronic candidosis not treated with cyclophosphamide antigen was detected in 4x concentrated serum between the fifth and sixth week. At about the same time antibodies were demonstrable and thereafter antigen was no longer detected. Maximum antibody titer occurred between the eight to 10th week and disappeared thereafter. If cyclophosphamide 30 mg/kg was given at this point, anticandida antibodies reappeared in high titers, persisted from three to four weeks and then disappeared. At autopsy no evidence of candidosis was present. If rabbits were pretreated with cyclophosphamide 60 mg/kg for one week before inoculation and given the drug weekly thereafter no antibody was detectable but antigen and antibody were present in body fluids (not serum) at post mortem.