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Protection of C3H/HE J mice from development of Candida albicans infection by oral administration of Juzen-taiho-to and its component, Ginseng radix: possible roles of macrophages in the host defense mechanisms.

Protective effect of a Japanese traditional herbal medicine, Juzen-taiho-to (TJ-48), which was recently reported to augment host-mediated antifungal actions, in Candida albicans-infected mice was further studied. TJ-48, given orally once daily for 5 consecutive days in a dose of 2 g/kg after intravenous infection of C. albicans, prolonged survival period of infected mice of a C3H/He J strain which is characteristic of functional deficiency of macrophages, but did not that of infected mice of a C3H/He N strain with normal macrophage function. Peritoneal macrophages obtained from C3H/He J mice showed a moderate inhibitory activity against Candida growth in vitro. The anti-Candida activity of the macrophages was augmented by the addition of TJ-48 or some component extracts of TJ-48 to the incubation medium. Among such active component extracts is an extract of Ginseng radix which was demonstrated to enhance the anti-Candida activity of macrophages in vitro and to prolong the survival time of C. albicans-infected C3H/He J mice without effect on C3H/He N mice. On the base of these findings, the mechanisms underlying the protective action of TJ-48 against systemic Candida infection was discussed in relation with its possible activity to activate the macrophage function.

Administration, Oral↗

Candida infections: an overview.

The range of human infections caused by the yeast Candida albicans and a handful of related species is considerable. They range from relatively trivial conditions such as oral and genital thrush to fatal, systemic superinfections in patients who are already seriously ill with other diseases. Interest in Candida infections, and in C. albicans in particular, has become huge in recent years as fatal infections have become more prevalent and new Candida-based pathologies have been recognized. There is now even a large pseudoscientific cult based on the notion that chronic allergy to Candida can cause all sorts of common illnesses. The medical importance of Candida infections and the scientific value of C. albicans as a model for fungal cellular development have stimulated enormous advances in our understanding of the epidemiology of candidosis, pathogenesis of the disease, and the genetics and biochemistry of C. albicans.

Candida↗

[Anti-Candida activities of azole antifungals in the presence of lysozyme in vitro].

The combined effects of lysozyme and various antifungal agents were investigated by microbroth dilution method against Candida albicans in vitro. Synergistic anti-Candida activity was observed between egg white lysozyme and itraconazole, clotrimazole, miconazole and lanoconazole. Similar, although not as clear, combination anti-Candida activities were seen in the cases of ketoconazole, bifonazole, amphotericin B and nystatin. Anti-Candida activity of fluconazole was not affected by the addition of lysozyme, however. Physiological roles of this combination effect in anti-Candida therapy by azole antifungals were discussed.

Anti-Infective Agents↗

[Cooperative inhibitory effects of cervical mucus and neutrophils on growth of Candida albicans].

Preparations of human cervical mucus were obtained from fifteen female volunteers with or without vaginal candidiasis. Their content of lactoferrin and inhibitory effects on the growth of Candida albicans were estimated. The concentration of lactoferrin in cervical mucus was measured by enzyme linked immunosorbent assay (ELISA). Lactoferrin concentration of the eleven preparations among them was more than 0.2 mg/ml. The effects of these cervical mucus preparations on Candida growth were examined in vitro. Candida growth was not inhibited by the addition of 1/200 diluted cervical mucus alone, however, anti-Candida activity of murine neutrophils was augmented by such an addition. These results suggest that the combination of neutrophils and cervical mucus may have an important role in defense against Candida infection in the vaginal mucosa.

Adult↗

Candida colonization in preterm babies admitted to neonatal intensive care unit in the rural setting.

PURPOSE: Candida colonization in neonates results in significant morbidity and mortality. The purpose of this study was to determine colonization of Candida spp. in preterm babies and identify the risk factors. METHODS: Swabs from oral, rectum, groin and umblicus of 103 preterm and 100 term neonates were obtained within 24 hours of birth, day three, day five, day seven and thereafter every week till the neonate was admitted in the neonatal intensive care unit (NICU). Swabs were also collected from the mother's vagina prior to delivery. Twice every month, air of the NICU was sampled by settle plate and swabs were collected from the hands of health care workers and inanimate objects of NICU. Identification and speciation was done by standard methods. Antibiotic sensitivity was studied against amphotericin B, ketoconazole and fluconazole by disk diffusion method. RESULTS: Colonization with Candida was significantly higher in preterms. Earliest colonization was of oral mucosa and 77.1% of the preterms had colonised at various sites by the first week of life. Significant risk factors in colonized versus non-colonized preterms were male sex, longer duration of rupture of membranes (DROM), administration of steroids and antibiotics and vaginal colonization of mothers, whereas those in preterms versus terms were low birth weight and gestational age. C. albicans was the commonest species, both in the colonized preterms (45.9%) and vagina of mothers. Resistance was seen to fluconazole and ketoconazole only. No Candida spp. was isolated from health care personnel or environment. CONCLUSIONS: Colonization of preterms by Candida is a significant problem in NICU and the significant risk factors observed in colonized preterms were male sex, longer DROM, administration of steroids and antibiotics and vaginal colonization of mothers.

Adult↗

Granulomatous hepatitis due to Candida albicans in patients with acute leukemia.

Deep-seated candidiasis developed after chemotherapy in two patients with acute leukemia. The patients developed granulomatous hepatitis caused by Candida albicans but had no evidence of disseminated candidiasis. Candida could not be isolated from liver biopsies taken from these patients, but yeast and filamentous fungal forms could be identified histochemically within the granulomas found in the biopsy specimens. Quantitation of anticandida antibody levels confirmed that deep-seated candida infection had occurred in both patients. The gastrointestinal tract was the only reasonable portal of entry for Candida in both patients. A diagnosis of candida-induced granulomatous hepatitis should be considered if high, unexplained fever and strikingly elevated serum alkaline phosphatase levels develop in a patient with acute leukemia after an intensive course of chemotherapy.

Adult↗

Molecular typing of Candida spp. by random amplification of polymorphic DNA and analysis of restriction fragment length polymorphism of ribosomal DNA repeats.

Random amplification of polymorphic DNA (RAPD) using an arbitrary oligonucleotide primer (5'-CGGTGCGACG) and analysis of restriction fragment length polymorphism of ribosomal DNA (rDNA-RFLP) after digestion of genomic DNA with restriction endonuclease EcoRI were investigated as tools for genotypic delineation beyond the species level of 91 Candida clinical isolates and four reference strains including 33 Candida albicans, 19 Candida tropicalis, 22 Candida krusei and 21 Candida (Torulopsis) glabrata. Results indicated that both techniques can be useful for typing isolates of the above species, although showing a variable discriminative potential with different species. As compared to RAPD fingerprinting, the discriminative potential of rDNA-RFLP appeared to be highest for C. albicans and lowest for C. glabrata, being overall similar for C. krusei and identical for C. tropicalis. A comparative analysis of the results obtained with the two typing techniques showed that, except for C. tropicalis, they were able to provide non-redundant information, and that their use in combination could enhance the discriminative potential for delineation among C. glabrata and C. krusei isolates.

Candida↗

[Lipolytic activity in some Candida strains (author's transl)].

The authors carried out an examination on the production of lipase in 300 Candida strains. The lipolytic activity was present in the majority of strains. In the 60 of the strains a more precise measurement of lipase production was performed qualitatively in a solid medium according to SIERRA (1957) and quantitatively in a liquid medium by titration with 0.1 N KOH. Furthermore, the correlation was determined between the production of lipase and the Candida growth. It was found that the qualitative proof of lipase in a solid medium according to SIERRA (1957) is a good informative method for determining lipolytic activity in Candidae. A much more sensitive method, however, is the quantitative method in a liquid medium; by this method the authors were successful in determining lipolytic activity even in some cases where the qualitative test was negative. On the whole, Candidae are lipolytically highly active. The mean values of lipase production in the Candida albicans cultures is 622 units in 1 ml of liquid medium; in other strains it is 798 units in 1 ml. There is a direct relation between the density of the culture and the amount of lipase produced.

Candida↗

[Identification of Candida albicans by specific primers of polymerase chain reaction and DNA probes].

Candida albicans is a pathogenic yeast. Two sets of universal primers were used for specific identification of Candida albicans with PCR-amplified ribosomal DNA internal transcribed spacers (ITS). Among the species of Candida, the amplified ITSI and ITSII of DNA fragments were similar in size. The PCR product was purified and labeled with digoxigenin and used as DNA probe in the detection with target DNA of Candida albicans by hybridization. Two sets of specific primers (CA1 and CA2 to amplify ITSI, CA3 and CA4 to amplify ITSII) were designed by alignment of ribosomal ITS sequence of pathogenic Candida albicans with other species to detect C. albicans by PCR. The sensitivity of PCR using the specific primers to detect pure culture of C. albicans was 0.1 ng (about 10(3)-10(4) cells). If the yeast cells were mixed with two other strains, there was a 10-fold decrease in sensitivity (1 ng or 10(4)-10(5) cells) under the same PCR conditions.

Base Sequence↗

[Nosocomial transmission of Candida albicans in newborn infants].

Candida spp. colonization in neonates occurs due to vertical or horizontal transmission. Preliminary studies determined that Candida albicans is the principal agent of these infections. In order to establish nosocomial transmission, 26 Candida albicans strains isolated from patients with candidosis hospitalized during a 18-month period in 2 neonatal intensive care units (NICU) from a pediatric hospital were studied. Fourteen isolates from patients and health care workers, involved in possible outbreaks of an intensive care unit (UCI) and a NICU from another pediatric hospital were also studied. All Candida albicans strains were genotyped by Southern blot hybridization with 27A. Isolates for outbreak confirmation were also hybridized with another specific Candida albicans probe, Ca3. Hybridization patterns demonstrated horizontal transmission in all the units studied. In a NICU, transmission among 4 patients during a 10-month period could be established and in the other NICU, 3 cases of transmission among 2 patients each were demonstrated in periods of 2 to 20 days. The outbreak studies showed the same strain isolated from 2 nurses and from one patient at the NICU and at the ICU identical strains were found in 3 patients. In this study, hybridization with Ca3 in addition to 27A probe did not increase discrimination power among isolates. Genotypic analysis allows, not only, determination of transmission and persistence of strains during prolonged periods or in sporadic outbreaks, but also facilitates necessary epidemiological decisions for optimizing nosocomial fungal infection control measures.

Candida albicans↗

Increased incidence of vulvovaginal candidiasis caused by Candida glabrata in Jordan.

Due to the rising importance of Candida glabrata and other non-albicans Candida as principle human opportunistic pathogens, 356 women with abnormal vaginal discharge who attended a private obstetrics and gynecology clinic in Amman, Jordan, between January 1999 and February 2001 were examined. The isolation rate of Candida spp. from high-vaginal swabs was 44.9%. CHROMagar Candida and conventional mycological methods identified six isolated Candida spp., including C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, and C. kefyr. The percentages of C. albicans, C. glabrata, and C. tropicalis isolates were 43.1%, 32.5%, and 8.1%, respectively. C. albicans was isolated in combination with C. tropicalis and C. krusei in two patients. Statistical analysis of the present results clearly show an increase in the incidence of vulvovaginal candidiasis caused by C. glabrata in the two study periods, 1994-1996 and 1999-2001 (P = 0.0186). In contrast, comparing the proportions of vulvovaginal candidiasis caused by C. albicans in the two periods, there was no significant difference. These results may have significant clinical implications, as C. glabrata are innately less susceptible to most antifungal agents than C. albicans; these findings support viewing this organism as a major pathogen.

Adolescent↗

Fluconazole susceptibility of Candida species in Singapore by disc diffusion test.

INTRODUCTION: Resistance of Candida species to fluconazole has been increasingly reported worldwide. To date, the prevalence of resistance to fluconazole in Singapore is unknown. The aim of this study was to use a newly described agar disc diffusion method to study levels of susceptibility of Candida species to fluconazole in several hospitals in Singapore. MATERIALS AND METHODS: Three hundred and ninety Candida isolates from clinical specimens collected from different sites were tested, of which 191 isolates (49.0%) were C. albicans, 69 (17.7%) were C. parapsilosis, 59 (15.1%) were C. glabrata, 51 (13.1%) were C. tropicalis and 4 (1.0%) were C. krusei. Susceptibility testing was performed using 25 micrograms fluconazole discs and standard Mueller-Hinton agar supplemented with 2% glucose and 0.5 microgram/mL of methylene blue. RESULTS: Overall, 381 (97.7%) isolates were susceptible, 6 (1.5%) were susceptible dose-dependent, and 3 (0.8%) were resistant to fluconazole. Of the individual species, 99.5% of C. albicans, 93.2% of C. glabrata, 0% of C. krusei, and 100% of C. parapsilosis, C. tropicalis and other Candida species were susceptible. CONCLUSION: The resistance of Candida species to fluconazole, as measured using a new disc diffusion method, is low in Singapore, with the exception of C. krusei. Fluconazole remains a useful agent for the treatment of candidiasis in this country.

Antifungal Agents↗

[Detection of phospholipidolytic Candida albicans isolated from saliva of children with Down's syndrome].

The childhood is one of the most propitious period of the life to the occurrence of infection by yeasts of the genus Candida. In children with Down's syndrome, besides the predispose factors to bucal candidiasis; macroglossia, bucal muscular incompetence, frequent respiratory diseases, motor difficulty and immunologic deficit are mentioned as additional elements for this fungus disease. It was verified that the children attacked by this syndrome have much more strains of Candida than other children. The aim of this study was to detect the prevalence of phospholipase producer, Candida on the saliva of children with Down's syndrome. Candida albicans was the only identified specie of Candida. The phospholipase production was found in isolated strains from both of study and control. However, the isolated strains of the group of children with Down's syndrome have strongly present phospholipidolitic.

Candida albicans↗

[The relationship between the presence of Candida colonization in the oropharynx and on the Blom-Singer voice prosthesis and its effect on the length of prosthesis use].

OBJECTIVES: We investigated the effect of oropharyngeal Candida colonization on the contamination of the Blom-Singer voice prosthesis and its lifetime. PATIENTS AND METHODS: The study included 26 male laryngectomized patients (age range 45 to 76 years) in whom the Blom-Singer low-pressure prosthetic valve inserted required removal due to improper functioning. All patients had postoperative radiotherapy. Patients who had nystatin therapy were excluded. At the time of removal, cultures were obtained from the esophageal end of the prosthesis and from the oropharynx to be examined with regard to Candida growth. RESULTS: Candida colonization was recovered from the cultures obtained on 20 prostheses (77%) and from 14 oropharyngeal specimens (54%). The presence of oropharyngeal colonization was always associated with that on prostheses. The average lengths of prosthesis use were 5.7 months (range 4 to 9 months) and 6.2 months (range 3 to 10 months) in patients with and without positive oropharyngeal Candida colonization, respectively (p>0.05). CONCLUSION: The results suggest that the presence of oropharyngeal Candida colonization has no effect on the prosthesis lifetime.

Aged↗

A comparison of the specificity and sensitivity of two Candida antigen assay systems for the diagnosis of deep candidiasis in patients with hematologic diseases.

BACKGROUND: Latex agglutination assay for detection of circulating Candida antigen (Cand-Tec, Ramco Laboratories), which is now commercially available, provides a rapid and simple means for the diagnosis and management of deep-seated Candida infections. MATERIAL/METHODS: The Cand-Tec microtiter system (Cand-Tec MT, Ramco Japan), new latex agglutination assay for Candida antigen, expresses Candida antigen level as the cutoff index (C.I.) value by means of colorimetric analysis and is expected to be more objective method. RESULTS: In this study, we evaluated the advantages, if any, of Cand-Tec MT compared with the original Cand-Tec for the diagnosis of deep-seated Candida infections in 25 patients with hematologic diseases. A total of 80 serum specimens were taken from the patients when they showed febrile neutropenia and were suspected of having infectious disease. The C.I. value in Cand-Tec MT well correlated with the Cand-Tec titer. The sensitivity and specificity of Cand-Tec MT were 100% and 80%, respectively. The change in C.I. value in the sera was followed up during antifungal therapy. The C.I. value decreased in 75% of cases that responded to antifungal therapy, but did not show any tendency in non-responsive cases. In some cases, the C.I. value showed improvement corresponding to the therapeutic effect, while the Cand-Tec titer did not. CONCLUSIONS: Cand-Tec MT is a useful method for the early diagnosis and accurate evaluation of the therapeutic effect of systemic candidiasis.

Antigens, Fungal↗

[A method for measuring the strength of adhesion of Candida albicans on epithelial cells].

A method on estimation of Candida albicans adhesion to epitheliocytes is proposed. The principle consists in the fact that while centrifuging epitheliocytes (1000 cycles/min, 10 min) with adhered Candida albicans through phycoll-verografin (1.077 g/cm3 density), Candida albicans cells having poor adhesion are separated from epitheliocytes trying to rise to the surface of phycoll-verografin. Candida albicans strongly adhered to epitheliocytes settle down to the bottom of test tube. In experiments with buccal epitheliocytes of healthy donors the number of strongly adhered Candida albicans ranged from 13% to 50% and they amounted to 37.0 +/- 7.8% on an average.

Candida albicans↗

[Identification of Candida dubliniensis strains using heat tolerance tests, morphological characteristics and molecular methods].

Described in 1995, Candida dubliniensis is a novel Candida species closely related to Candida albicans due primarily to its ability to produce germ tube and chlamydospores. Given these phenotypic similarities between the two species, C. dubliniensis cannot be readily distinguished from Candida albicans by routine laboratory work-up. We explored the frequency of isolation of C. dubliniensis among 213 strains previously defined as C. albicans based on their ability to produce germ tube. The test isolates were initially examined for their morphological features on cornmeal tween 80 agar, inability to grow at 45 degrees C, and the biochemical assimilation profile (ID 32C system, bioMerieux, France). Among all, 2 (0.9%) of the isolates were identified as C. dubliniensis based on the production of numerous chlamydospores in chains on cornmeal tween 80 agar and the lack of growth at 45 degrees C. The assimilation profile of these isolates was found to be in accordance with this identification. In an effort to confirm the identification, polymerase chain reaction (PCR) studies were carried out by using the C. dubliniensis specific primer set, DUBF and DUBR. Both of the isolates yielded C. dubliniensis-specific 288 base pair amplification products, confirming the previous identification obtained with the initial screening tests. The isolates were found to be susceptible to fluconazole and itraconazole, and generated amphotericin B minimal inhibitory concentrations of 0.5-1 microgram/ml by NCCLS M27-A2 microdilution method. These data suggest that the isolation rate of C. dubliniensis among our clinical isolates is low. The morphological features on cornmeal tween 80 agar and the lack of ability to grow at 45 degrees C appear as reliable, cheap, and practical screening tests in initial identification of C. dubliniensis among germ tube-producing Candida strains.

Antifungal Agents↗

BACTERIAL ENDOCARDITIS WITH CANDIDA ALBICANS SUPERINFECTION.

Clinical and pathological features of two fatal cases of bacterial endocarditis with Candida albicans superinfection are described. One patient presented with combined Streptococcus viridans and Candida endocarditis of the aortic valve. The second patient, an addict to paregoric injected intravenously, developed Staphylococcus aureus of the tricuspid valve with eventual Candida endocarditis. The responsible organisms were identified from blood cultures during the hospital course, and by culture or tissue section of postmortem material. Candida endocarditis has emerged as a disease entity in the past 20 years. The incidence is increasing and patients with bacterial endocarditis are among those at risk. Antibiotic therapy appeared to facilitate the development of Candida endocarditis in these two cases.

Anti-Bacterial Agents↗