Fungal Genet Biol, 1996 Mar, 20(1), 79 - 83 Dibutyryl cyclic AMP-enhanced germ tube formation in exponentially growing Candida albicans cells; Niimi M; Competence in germ tube formation for exponential phase cells of several Candida albicans was low (less than 14%) in 0.1 M phosphate buffer (pH 6.8) containing 1 mM proline . Addition of 5 mM dibutyryl cyclic AMP (cAMP), a lipophilic cAMP analog, to the induction medium increased germ tube formation up to 50% . This enhancement occurred only when the cells were grown in medium lacking glucose or fructose as a carbon source . N-Acetylglucosamine-induced germ tube formation was enhanced by dibutyryl cAMP under similar conditions, but the enhancement was only slight . Cyclic GMP (cGMP) or AMP did not enhance germ tube formation, while dibutyryl cGMP, theophylline, and butyric acid were inhibitory . These results show that dibutyryl cAMP stimulation of the germ tube formation depends on the growth phase and the nutritional status of the cell. Acta Cytol, 1996 Mar-Apr, 40(2), 196 - 8 Fine needle aspiration biopsy in patients with diffusely enlarged spleens; Lishner M et al.; OBJECTIVE: To evaluate the diagnostic value and potential risk of fine needle aspiration biopsy (FNAB) of the spleen in patients with diffuse splenomegaly due to an undetermined cause . STUDY DESIGN: Retrospective evaluation of the medical records and cytologic material from 58 patients on whom FNAB was performed between 1967 and 1993 . RESULTS: Sixty-five FNABs were performed on 58 patients . Lymphoproliferative diseases were found in six; in four additional cases, metastatic adenocarcinoma, sarcoidosis, Candida albicans and enterococcal infection were demonstrated . The remaining 55 biopsies either showed normal splenic tissue or were nondiagnostic . No complications were recorded . CONCLUSION: Splenic FNAB may be useful in some patients with diffuse splenomegaly . The diagnostic yield is rather low . The procedure, however, is simple, safe and well tolerated. J Infect Dis, 1996 Mar, 173(3), 684 - 90 Identification of a glucan-associated enolase as a main cell wall protein of Candida albicans and an indirect target of lipopeptide antimycotics; Angiolella L et al.; Growth-subinhibitory nonlytic doses of cilofungin (lipopeptide antibiotic affecting (1,3)-beta-D-glucan synthesis) inhibited the incorporation of 46- to 48-kDa glucan-associated (46K) protein into the growing cell wall of Candida albicans . The purified 46K protein constituent strongly reacted with a monoclonal antibody against enolase, a major cytoplasmic enzyme of the fungus . In addition, two internal fragments of 12- and 15-amino acid residues from a tryptic digest of 46K protein showed 100% identity with amino acids in positions 34-45 and 66-80 of enolase . By immunoelectron microscopy with polyclonal and monoclonal anti-enolase antibodies, the 46K protein was clearly detected in the inner layers of the fungal cell wall . Thus, consistent with the proposed immunogenic and diagnostic roles of enolase in candidiasis, biochemical, immunochemical, and ultrastructural evidence strongly suggest that the cilofungin-susceptible 46K protein is a cell wall-associated form of this enzyme. Anesth Analg, 1996 Mar, 82(3), 475 - 8 Growth of microorganisms in propofol, thiopental, and a 1:1 mixture of propofol and thiopental; Crowther J et al.; To assess and compare the growth of four microorganisms in solutions of intravenous anesthetics, known quanta of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were inoculated into propofol, thiopental, a 1:1 mixture of propofol and thiopental, and normal saline . All microorganisms were taken from standard stock cultures and incubated for 24 h (48 h for C . albicans) . Growth of microorganism in each drug was compared by counting the number of colony forming units (CFUs) grown from a subculture of each inoculated anesthetic at 0, 3, 6, 12, and 24 h . The study shows that propofol strongly supports the growth of E . coli and C . albicans but is bacteriostatic toward S . aureus and weakly bactericidal toward P . aeruginosa . In contrast, both thiopental and the 1:1 mixture of propofol and thiopental behaved differently, exhibiting markedly bactericidal properties toward E . coli, S . aureus, and P . aeruginosa and a bacteriostatic effect on C . albicans . This finding supports recommendations that a strict aseptic technique should be used when handling propofol and that the contents of an ampoule should be used within 6 h of aspirating . The measured high pH of both thiopental and the 1:1 mixture of propofol and thiopental compared to propofol alone suggests pH to be a major factor in determining whether a given drug will support microbial growth. J Immunol, 1996 Mar 1, 156(5), 1989 - 96 Haptoglobin phenotyping by newly developed monoclonal antibodies . Demonstration of haptoglobin uptake into peripheral blood neutrophils and monocytes; Wagner L et al.; We have generated two IgG murine mAbs that recognize native human haptoglobin (Hp) . These mAbs, 3A8 and 4B2, efficiently bind to the Hp complex regardless of the serum donor's phenotype . The specificity of mAb 3A8 was confirmed by immunoaffinity purification of 3A8-binding material from human serum and subsequent N-terminal amino acid sequencing of the invariant 40-kDa chain . mAb 3A8 and 4B2 were also reactive with cell-associated Hp when studied by immunocytochemistry . When human peripheral blood leukocytes were tested, 90% of the granulocytes and a lesser (and variable) fraction of monocytes displayed an intense intracytoplasmatic granular staining . This was confirmed by flow cytometric analysis of permeabilized leukocytes and by demonstrating the presence of Hp (of the expected Hp serum phenotype) in extracts of washed granulocytes by immunoblotting . Leukocytes obtained from a Hp phenotype 2-2 donor, incubated in culture medium supplemented with 10% serum from a donor possessing the Hp 1-1 phenotype, contained both Hp phenotypes when analyzed by immunoblotting after a 6-h incubation period . In addition, Hp was actively exocytosed by granulocytes following their exposure to Candida albicans . These observations suggest that exogenous Hp is concentrated within granulocytes and not synthesized de novo and is, in turn, exocytosed following neutrophil activation . Northern blotting analysis is consistent with the lack of haptoglobin gene transcription in granulocytes . These findings together with the earlier observations that Hp modulates granulocyte activity suggest that Hp levels may be enhanced locally at sites of inflammation to modulate granulocyte activity. J Med Chem, 1996 Feb 16, 39(4), 892 - 903 High-affinity inhibitors of dihydrofolate reductase: antimicrobial and anticancer activities of 7,8-dialkyl-1,3-diaminopyrrolo{3,2-f}quinazolines with small molecular size; Kuyper LF et al.; A series of 7,8-dialkylpyrrolo{3,2-f}quinazolines were prepared as inhibitors of dihydrofolate reductase (DHFR) . On the basis of an apparent inverse relationship between compound size and antifungal activity, the compounds were designed to be relatively small and compact . Inhibitor design was aided by GRID analysis of the three-dimensional structure of Candida albicans DHFR, which suggested that relatively small, branched alkyl groups at the 7- and 8-positions of the pyrroloquinazoline ring system would provide optimal interactions with a hydrophobic region of the protein . The compounds were potent inhibitors of fungal and human DHFR, with K(i) values as low as 7.1 and 0.1 pM, respectively, and were highly active against C . albicans and an array of tumor cell lines . In contrast to known lipophilic inhibitors of DHFR such as trimetrexate and piritrexim, members of this series of pyrroloquinazolines were not susceptible to P-glycoprotein-mediated multidrug resistance and also showed significant distribution into lung and brain tissue . The compounds were active in lung and brain tumor models and displayed in vivo activity against Pneumocystis carinii and C . albicans. Mol Gen Genet, 1996 Feb 5, 250(2), 214 - 22 chs-4, a class IV chitin synthase gene from Neurospora crassa; Din AB et al.; In Saccharomyces cerevisiae, most of the cellular chitin is produced by chitin synthase III, which requires the product encoded by the CSD2/CAL1/DIT101/KT12 gene . We have identified, isolated and structurally characterized as CSD2/CAL1/DIT101/KT12 homologue in the filamentous ascomycete Neurospora crassa and have used a "reverse genetics" approach to determine its role in vivo . The yeast gene was used as a heterologous probe for the isolation of a N . crassa gene(designated chs-4) encoding a polypeptide belonging to a class of chitin synthases which we have designated class IV . The predicted polypeptide encoded by this gene is highly similar to those of S . cerevisiae and Candida albicans . N . crassa strains in which chs-4 had been inactivated by the Repeat-Induced point mutation (RIP) process grew and developed in a normal manner under standard growth conditions . However, when grown in the presence of sorbose (a carbon source which induces morphological changes accompanied by elevated chitin content), chitin levels in the chs-4RIP strain were significantly lower than those observed in the wild type . We suggest that CHS4 may serve as an auxiliary enzyme in N . crassa and that, in contrast to yeasts, it is possible that filamentous fungi may have more than one class IV chitin synthase. Lett Appl Microbiol, 1996 Feb, 22(2), 125 - 8 Application of RAPD and restriction enzyme analysis to the study of oral carriage of Candida albicans; Howell SA et al.; The genetic similarity of nineteen isolates of Candida albicans from four patients were compared by restriction fragment length polymorphism (RFLP) using EcoRI or HinfI, which both detected five types, and by random amplification of polymorphic DNA (RAPD), which detected three types . Phenotypically unusual isolates also produced distinct patterns with both typing systems demonstrating the carriage of two groups of C . albicans as well as the presence of more than one type in some subjects . Methods of DNA preparation were compared for the production of reproducible patterns; including using the supernatant fluid of boiled intact or spheroplasted cells for RAPD, and DNA precipitated from chloroform extracted cell lysate for RFLP and RAPD . Consistent patterns were produced from the DNA precipitate by RAPD and after an additional precipitation by RFLP, thus removing the necessity for lengthy extraction procedures or the use of toxic chemicals for purification. Inflammation, 1996 Feb, 20(1), 107 - 22 Candida albicans induces the release of inflammatory mediators from human peripheral blood monocytes; Castro M et al.; Candida albicans (C . albicans) is a major nosocomial pathogen . We examined arachidonic acid (AA) and cytokine production by monocytes stimulated with C . albicans . {14C}-AA labeled monocytes released 8.9 +/- 2.3% of the incorporated AA following stimulation with live C . albicans (C . albicans: monocyte of 16:1) (P = 0.0002) . Prior studies indicate that soluble alpha-mannans and beta-glucans antagonize mannose and beta-glucan receptors, respectively . Preincubation of monocytes with alpha-mannan (100 micrograms/ml) caused 45.8 +/- 5.7% inhibition of {14C}-AA release, whereas beta-glucan (100 micrograms/ml) yielded 43.7 +/- 6.0% inhibition (P < 0.05 for each compared to control) . Additionally, monocytes stimulated with C . albicans also released interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) . However, alpha-mannan or beta-glucan failed to inhibit IL-1 beta release . These data indicate that C . albicans induces monocytes to release AA and inflammatory cytokines . Furthermore, AA, but not cytokine liberation, is partially mediated by alpha-mannan and beta-glucan components of the fungus. Hautarzt, 1996 Feb, 47(2), 136 - 9 {Clinical fluconazole and itraconazole resistance of oro-gastrointestinal candidiasis in a patient with AIDS}; Tebbe B et al.; We report on a 32-year-old male patient with advanced acquired immunodeficiency syndrome (AIDS), who had severe candidiasis of the gastrointestinal tract . Treatment with fluconazole, 200 mg/day, was introduced . After oral intake of fluconazole over 5 months itraconazole 200 mg/day was given for 1 month . However, fungal infection still persisted . The antifungal activity of fluconazole, itraconazole and ketoconazole against Candida albicans was evaluated by means of the microdilution test by determining the 90% inhibitory concentration of each drugs . A high minimal inhibitory concentration (MIC) was detected for fluconazole (50 micrograms/ml) revealing fluconazole resistance . The susceptibility to itraconazole was borderline (MIC 0.125 micrograms/ml) and that to ketoconazole was markedly lowered (MIC 0.25 micrograms/ml) . Plasma levels of itraconazole were also found to be lowered . In HIV patients the gastrointestinal absorption of azole derivatives is often reduced . Therefore, the clinical resistance of Candida albicans to itraconazole can be explained by reduced susceptibility after azole therapy and also by the decreased absorption of the drug in HIV patients. Rinsho Ketsueki, 1996 Feb, 37(2), 134 - 8 -Rejection of an allogeneic bone marrow graft following successful treatment of severe graft-versus-host disease (GVHD)}; Sugimori N et al.; A 38-year-old female with acute myelogenous leukemia (M2) received an allogeneic bone marrow graft from an HLA-DR one locus-mismatched sister during the first remission . The conditioning regimen consisted of busulfan and cyclophosphamide . Acute graft-versus-host disease (GVHD) developed on day 11 after transplantation . Although the GVHD was successfully treated with methylprednisolone, peripheral blood neutrophils that had begun to increase disappeared in association with improvement of the GVHD and graft rejection was eventually diagnosed . The second bone marrow transplantation from the same donor ended up with engraftment failure . She died of sepsis due to Candida albicans following the development of Epstein-Barr virus-associated B-lymphoproliferative disorder . The clinical course of this patient indicates that successful therapy of severe GVHD with methylprednisolone may lead to marrow graft rejection. Clin Infect Dis, 1996 Feb, 22(2), 366 - 8 Fungal endocarditis in premature infants: case report and review; Mayayo E et al.; Fungal endocarditis in premature infants has rarely been reported; only 16 cases have been described . We present a fatal case of endocarditis due to Candida albicans in a patient requiring neonatal intensive care and parenteral nutrition via a central venous catheter; there were no preexisting pathological abnormalities . The patient had sepsis with multisystem organ failure, resulting in death . A postmortem examination was performed, and the most important findings are presented . The literature on fungal endocarditis in premature infants is reviewed as well. Clin Infect Dis, 1996 Feb, 22(2), 348 - 54 Successful treatment of fungal prosthetic valve endocarditis: case report and review; Gilbert HM et al.; We report a case of Candida albicans prosthetic valve endocarditis in a patient who was still alive 1 year following a homograft aortic root and valve replacement and antifungal therapy . Only 33 other cases of successfully treated fungal prosthetic valve endocarditis have been reported . We review these 33 cases and six cases of late recurrence following treatment, as well as the clinical features, diagnosis, and options for treatment of fungal prosthetic valve endocarditis. Clin Exp Allergy, 1996 Feb, 26(2), 164 - 70 A comparison of the development of antibody responses to the polysaccharide antigen (Candida albicans mannan) in atopic and healthy infants and children; Nermes M et al.; BACKGROUND: Defective antibody response against bacterial polysaccharide antigens is known to be associated with recurrent pyogenic infections . The role of childhood allergy as a risk factor for repeated infections with capsulated micro-organisms has been controversial . OBJECTIVE: To compare the development of polysaccharide specific antibody responses in atopic and healthy infants and children . METHODS: The antibody responses against a common polysaccharide antigen, Candida albicans mannan, were studied longitudinally in 18 atopic and 19 non-atopic children over the first 5 years of life . Determinations of IgA, IgG and IgM antibodies were carried out by enzyme-linked immunosorbent assay and IgE antibodies by nitrocellulose-based radioallergosorbent test . RESULTS: The polysaccharide specific antibody responses were similar in both groups, except that anti-mannan IgM levels were higher at 5 years in the atopic children (P < 0.05, student's t-test) . CONCLUSION: Atopic children are not more susceptible to bacterial infections on the basis of poorer ability to produce antibodies against polysaccharide antigens. Antimicrob Agents Chemother, 1996 Feb, 40(2), 443 - 7 Characterization of squalene epoxidase activity from the dermatophyte Trichophyton rubrum and its inhibition by terbinafine and other antimycotic agents; Favre B et al.; Squalene epoxidase (SE) is the primary target of the allylamine antimycotic agents terbinafine and naftifine and also of the thiocarbamates . Although all of these drugs are employed primarily in dermatological therapy, SE from dermatophyte fungi has not been previously investigated . We report here the biochemical characterization of SE activity from Trichophyton rubrum and the effects of terbinafine and other inhibitors . Microsomal SE activity from T . rubrum was not dependent on soluble cytoplasmic factors but had an absolute requirement for NADPH or NADH and was stimulated by flavin adenine dinucleotide . Kinetic analyses revealed that under optimal conditions the Km for squalene was 13 microM and its Vmax was 0.71 nmol/h/mg of protein . Terbinafine was the most potent inhibitor tested, with a 50% inhibitory concentration (IC50) of 15.8 nM . This inhibition was noncompetitive with regard to the substrate squalene . A structure-activity relationship study with some analogs of terbinafine indicated that the tertiary amino structure of terbinafine was crucial for its high potency, as well as the tert-alkyl side chain . Naftifine had a lower potency (IC50, 114.6 nM) than terbinafine . Inhibition was also demonstrated by the thiocarbamates tolciclate (IC50, 28.0 nM) and tolnaftate (IC50, 51.5 nM) . Interestingly, the morpholine amorolfine also displayed a weak but significant effect (IC50, 30 microM) . T . rubrum SE was only slightly more sensitive (approximately twofold) to terbinafine inhibition than was the Candida albicans enzyme . Therefore, this difference cannot fully explain the much higher susceptibility (> or = 100-fold) of dermatophytes than of yeasts to this drug . The sensitivity to terbinafine of ergosterol biosynthesis in whole cells of T . rubrum (IC50, 1.5 nM) is 10-fold higher than that of SE activity, suggesting that the drug accumulates in the fungus. Antimicrob Agents Chemother, 1996 Feb, 40(2), 419 - 25 Correlation between rhodamine 123 accumulation and azole sensitivity in Candida species: possible role for drug efflux in drug resistance; Clark FS et al.; A wide variety of prokaryotic and eukaryotic cells exhibit a multidrug resistance (MDR) phenotype, indicating that resistance to potentially toxic compounds is mediated by their active efflux from the cell . We have sought to determine whether resistance to azoles in some strains of Candida species may be due in part to active drug efflux . Rhodamine 123 (Rh123) is a fluorescent compound that is transported by a wide variety of MDR cell types . We have shown that certain azole-resistant strains of Candida albicans, C . glabrata, and C . krusei accumulate less Rh123 than azole-susceptible ones . In C . albicans, Rh123 accumulation was growth phase and temperature dependent and was increased by proton uncouplers and by reserpine, an MDR modulator . This is consistent with an energy-dependent efflux mechanism for Rh123, mediated by an MDR transporter . In C . glabrata, but not in C . albicans, there was competition between Rh123 and fluconazole for efflux . Thus, in C . glabrata, Rh123 and fluconazole appear to be transported via a common MDR-like transporter, whereas in C . albicans, the Rh123 transporter does not appear to transport azoles. J Clin Microbiol, 1996 Feb, 34(2), 474 - 6 Molecular probe for typing strains of Candida albicans; Postlethwait P et al.; A method for separating strains of Candida albicans into nine possible groups was devised by using a cDNA probe for enolase and Southern blot analysis . Twenty-three isolates of C . albicans were found to be distributed among eight of the groups . Fifteen isolates from a single hospital segregated into four of the groups. Wei Sheng Wu Xue Bao, 1996 Feb, 36(1), 73 - 5 {Preparation of beta-1,3-glucan synthase and its application to the screening of antifungal antibiotics}; Zheng D et al.; beta-1,3-glucan synthase was obtained as a particulate fraction from cell-free extracts prepared after mechanical breakage cells of Candida albicans . Some properties of the glucan synthase were investigated . Using it as a target for screening for novel antifungal compounds, we obtained strains whose products showed differential enzyme inhibition. Immunopharmacol Immunotoxicol, 1996 Feb, 18(1), 73 - 89 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; Akagawa G et al.; 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. Contracept Fertil Sex, 1996 Feb, 24(2), 163 - 5 {Comparison of the effects of fenticonazole and econazole on the aspartic proteinase secreted by Candida albicans}; De Bernardis F et al.; In this note, the effect of fenticonazole on secretory aspartic proteinase of the human opportunistic fungus Candida albicans is shown, in a comparison with econazole . Both antigenic and enzymatic assays demonstrate that fenticonazole, in contrast to econazole, greatly reduces the production of the virulence enzyme by stationary-phase C . albicans . This inhibitory effect was specific and was not mediated by the inhibition of fungal growth . These results confirm fenticonazole's unique property, already shown in previous studies. Oral Microbiol Immunol, 1996 Feb, 11(1), 59 - 61 Coaggregation of Candida albicans with oral Actinomyces species; Grimaudo NJ et al.; Eight strains of Actinomyces were examined for their ability to coaggregate in vitro with four strains of Candida albicans . The Actinomyces coaggregated to various degrees with all of the Candida strains . Exposure of the Candida but not the Actinomyces to heat, trypsin, proteinase K, amphotericin B or trichodermin abolished coaggregation . All sugars tested did not inhibit any of the reactions . All coaggregating pairs were disaggregated by the addition of SDS, but nonionic detergents had no effect . The addition of urea or EDTA completely reversed coaggregation . Actinomyces strains were sensitive to periodate oxidation, whereas the Candida strains were unaffected . These data suggest that the coaggregations involve a protein on the Candida surface that may interact with carbohydrates or carbohydrate-containing molecules on the surface of the Actinomyces . These observations expand the known range of intergeneric coaggregations occurring between human oral microbes and indicate that coaggregation of C . albicans and Actinomyces may be an important factor in oral colonization by this yeast. Surgery, 1996 Feb, 119(2), 178 - 85 Granulocyte-macrophage colony-stimulating factor inhibits tumor growth during the postoperative period; Hill AD et al.; BACKGROUND . Granulocyte-macrophage colony-stimulating factor (GM-CSF) may have important antineoplastic properties because it induces macrophage tumoricidal activity in vitro . We examined the inhibitory effect of GM-CSF on tumor growth in a murine carcinoma model and whether this inhibitory effect would persist during the postoperative period . Potential macrophage-mediated mechanisms were studied . METHODS . The effect of GM-CSF on macrophage function in vitro was assessed by measuring superoxide anion and interleukin-6 production, percentage phagocytosis of Candida albicans, and percentage Ia expression . GM-CSF's effect on tumor volume was assessed first in a murine tumor model and second to examine whether these effects also occurred during the postoperative period in the same model after laparotomy . Macrophage function in the latter study was assessed by measuring superoxide anion, cytotoxicity, and tumor necrosis factor production . RESULTS . GM-CSF treatment was associated with a decrease in tumor volume on day 4 after the initiation of GM-CSF treatment (0.93 +/- 0.08 cm3 for control versus 0.34 +/- 0.08 cm3 for GM-CSF; p < 0.05) . This effect was also seen after laparotomy (1.07 +/- 0.2 cm3 for laparotomy+saline versus 0.16 +/- 0.04 cm3 for laparotomy+GM-CSF, p < 0.05) . In vivo macrophage function showed increased superoxide anion, cytotoxicity, and tumor necrosis factor-alpha production from macrophages obtained from GM-CSF treated animals compared with saline treated controls . CONCLUSIONS . Tumor growth is inhibited by GM-CSF treatment, and this effect also occurs after laparotomy . Thus, GM-CSF may have a therapeutic role in the treatment of the tumor bearing host after operation. J Infect Dis, 1996 Feb, 173(2), 495 - 8 Silver iontophoretic catheter: a prototype of a long-term antiinfective vascular access device; Raad I et al.; A silver iontophoretic catheter (SIC) was developed consisting of two electrically charged parallel silver wires helically wrapped around the proximal segment of a vascular catheter . In vitro and in vivo activities of this catheter were compared with those of an aseptic catheter coated with chlorhexidine and silver sulfadiazine (CH/SS) . The SIC demonstrated broad-spectrum in vitro inhibitory activity against bacteria and Candida albicans comparable to that of the CH/SS-coated catheter . The durability of activity was determined by incubating catheters in serum at 37 degrees C for various time intervals . After 30 days, the antimicrobial activity of the SIC did not change significantly, while that of the CH/SS-coated catheter was reduced to a suboptimal level . In a rabbit model, the SIC was safe and significantly more efficacious than the CH/SS-coated catheter in preventing colonization with Staphylococcus aureus (P < .05) . The SIC has broad-spectrum inhibitory activity of long durability and is highly efficacious in preventing colonization in vivo. J Infect Dis, 1996 Feb, 173(2), 425 - 31 A murine model of Candida glabrata vaginitis; Fidel PL Jr et al.; Vaginal Candida glabrata infections have increased significantly in recent years and are particularly common in women with uncontrolled diabetes mellitus . Efforts to understand the pathogenesis and treatment of this infection have been hindered by the lack of experimental animal models . Before onset of hyperglycemia, nonobese diabetic (NOD) mice inoculated intravaginally with clinical C . glabrata isolates were shown to support high vaginal titers of C . glabrata for > 14 days with evidence for superficial invasion of vaginal epithelial tissue . In contrast, congenic diabetic-resistant mice and mice susceptible to Candida albicans infections were significantly less susceptible to vaginal infection by C . glabrata, suggesting a potential link between the susceptibility of NOD mice to diabetes and their susceptibility to vaginal C . glabrata infections . This animal model of C . glabrata vaginitis provides a means to study the genetics and pathogenesis of C . glabrata infections and to evaluate the efficacy of antimycotic agents against C . glabrata. J Infect Dis, 1996 Feb, 173(2), 418 - 24 The broad-spectrum activity and efficacy of catheters coated with minocycline and rifampin; Raad I et al.; The in vitro and in vivo activities of catheters coated with minocycline and rifampin and with chlorhexidine gluconate and silver sulfadiazine were evaluated . When incubated in serum at 37 degrees C, the half-life of the inhibitory activity of catheters coated with minocycline and rifampin was 25 days compared with 3 days for catheters coated with chlorhexidine gluconate and silver sulfadiazine . In a rabbit model, catheters coated with minocycline and rifampin were significantly more efficacious than catheters coated with chlorhexidine and silver sulfadiazine in preventing colonization and infection with Staphylococcus aureus (P < .05) . Catheters coated with minocycline and rifampin demonstrated broad-spectrum in vitro inhibitory activity against gram-positive bacteria, gram-negative bacteria, and Candida albicans that was significantly superior to the inhibitory activity of catheters coated with chlorhexidine gluconate and silver sulfadiazine (P < .01) . Minocycline and rifampin were also highly efficacious in preventing colonization and infection in vivo. Infect Immun, 1996 Feb, 64(2), 466 - 71 Elevated aspartic proteinase secretion and experimental pathogenicity of Candida albicans isolates from oral cavities of subjects infected with human immunodeficiency virus; De Bernardis F et al.; Isolates of Candida albicans from the oral cavities of subjects at different stages of human immunodeficiency virus (HIV) infection or uninfected controls were examined for (i) production of aspartic proteinase(s), a putative virulence-associated factor(s); (ii) the presence in the fungal genome of two major genes (SAP1 and SAP2) of the aspartic proteinase family; and (iii) experimental pathogenicity in a murine model of systemic infection . It was found that the fungal isolates from symptomatic patients secreted, on average, up to eightfold more proteinase than the isolates from uninfected or HIV-infected but asymptomatic subjects . This differential property was stably expressed by the strains even after years of maintenance in stock cultures . Moreover, representative high-proteinase isolates were significantly more pathogenic for mice than low-proteinase isolates of C . albicans . The characters high proteinase and increased virulence were not associated with a single molecular type or category identifiable through DNA fingerprinting or pulsed-field electrophoretic karyotype, and both SAP1 and SAP2 genes were present in both categories of isolates, on the same respective chromosomes . In conclusion, our data suggest that during HIV infection more-virulent strains or biotypes of C . albicans which are identifiable by direct analysis of virulence determinants are selected . It also appears that the biotype switch to increased aspartic proteinase and virulence properties occurs before the HIV-infected subject enters the symptomatic stage and overt AIDS. Proc Natl Acad Sci U S A, 1996 Jan 9, 93(1), 357 - 61 Cloning and expression of a gene encoding an integrin-like protein in Candida albicans; Gale C et al.; The existence of integrin-like proteins in Candida albicans has been postulated because monoclonal antibodies to the leukocyte integrins alpha M and alpha X bind to blastospores and germ tubes, recognize a candidal surface protein of approximately 185 kDa, and inhibit candidal adhesion to human epithelium . The gene alpha INT1 was isolated from a library of C . albicans genomic DNA by screening with a cDNA probe from the transmembrane domain of human alpha M . The predicted polypeptide (alpha Int1p) of 188 kDa contains several motifs common to alpha M and alpha X: a putative I domain, two EF-hand divalent cation-binding sites, a transmembrane domain, and a cytoplasmic tail with a single tyrosine residue . An internal RGD tripeptide is also present . Binding of anti-peptide antibodies raised to potential extracellular domains of alpha Int1p confirms surface localization in C . albicans blastopores . By Southern blotting, alpha INT1 is unique to C . albicans . Expression of alpha INT1 under control of a galactose-inducible promoter led to the production of germ tubes in haploid Saccharomyces cerevisiae and in the corresponding ste12 mutant . Germ tubes were not observed in haploid yeast transformed with vector alone, in transformants expressing a galactose-inducible gene from Chlamydomonas, or in transformants grown in the presence of glucose or raffinose . Transformants producing alpha Int1p bound an anti-alpha M monoclonal antibody and exhibited enhanced aggregation . Studies of alpha Int1p reveal novel roles for primitive integrin-like proteins in adhesion and in STE12-independent morphogenesis. Mycoses, 1996, 39 Suppl 2, 1 - 11 {Susceptibility testing of fluconazole: evaluation of a multicenter study of the working group "Clinical Mycology" of the German Speaking Mycological Society}; Schmalreck AF; In a collaborative study for in vitro testing of fluconazole against clinical yeast isolates participated 21 laboratories of the working group "Clinical Mycology" of the German Speaking Mycological Society . In these centers, according to a standard test protocol 1181 clinical isolates from 1033 patients were tested to their susceptibility against fluconazole by microdilution, agar diffusion and partly by agar dilution . Approximately 600 strains (59.1%) of the collective of 1106 isolates sent to a reference center underwent retesting in one laboratory (center 13) . These strains demonstrated almost the same species distribution as the total collective . For 80% of all isolates a MIC of < or = 4 micrograms/ml and for 90% of the Candida albicans strains a MIC of < or = 2 micrograms/ml has been determined . Only approx, 9% of all isolates (4% with Candida albicans) showed a MIC of < or = 25 micrograms/ml . By parallel testing of 10 control strains issued by the reference center to the laboratories, the inter- and intra-laboratory comparability of the susceptibility testing of fluconazole was checked . The results demonstrated that under appropriate technical prerequisites and standardised test conditions, the methods used routinely in bacteriology microdilution, agar dilution and agar diffusion may also be applied in a reproducible way in the routine mycological laboratory for the susceptibility testing of yeasts. Int J Tissue React, 1996, 18(4-6), 109 - 14 The macrophagic activity of patients affected by pneumonia or chronic obstructive pulmonary disease; Ferrara F et al.; The function of alveolar macrophages (AMS) in patients with pneumonia (n = 7) (Group A) and chronic obstructive pulmonary disease (COPD) (n = 11) (Group B) was investigated by evaluating the rate of phagocytosis and of the intracellular killing . A control group of healthy subjects (n = 8) was also included . Phagocytosis frequency (PHF), phagocytosis index (PHI) and intracellular killing towards Candida albicans were then evaluated . PHF and PHI were found to be significantly (p < 0.05) lower in Group B patients than in the control group, while intracellular killing showed a behaviour similar to controls . PHF and PHI values observed in the patients of Group A and in the control group did not show any significant difference; the intracellular killing rate proved on the contrary to be significantly (p < 0.05) lower than that observed in the controls. Exp Clin Immunogenet, 1996, 13(3-4), 161 - 72 Temperature-dependent surface expression of the beta-2-integrin analogue of Candida albicans and its role in adhesion to the human endothelium; Wurzner R et al.; Candida albicans has become one of the most important pathogens in intensive care units . Adherence of C . albicans to the vascular endothelium is believed to represent a critical step in the pathogenesis of disseminated candidiasis and may involve molecules analogous to human beta 2-integrins such as the complement receptor 3 (CR3) analogue of C . albicans (C.a.-CR3) . Its expression was detected by a sensitive rosetting assay when Candida was present in its hyphal form but not in its yeast form, the latter being generally considered to be less pathogenic . However, the presence of hyphae alone was not sufficient: C.a.-CR3 expression was found to be temperature-dependent for 4 (out of 10) clinical isolates . Two rosetted better after growth at 30 degrees C, the other 2 after growth at 37 degrees C . This temperature dependence was most pronounced for 1 laboratory strain: C.a.-CR3 expression was best at 30 degrees C and markedly decreased with increasing temperatures . At 37 degrees C no rosettes were detected at all . Modifications of the culture conditions (e.g . agitation, pH) exerted a marked influence on the morphology of this strain but always allowed rosette formation once hyphae were formed at 30 degrees C . However, none of these modifications was able to induce rosettes at 37 degrees C . Adhesion of C . albicans isolates to an endothelial cell line was also temperature-dependent but not strongly correlated with C.a.-CR3 expression . Most strains exhibited a better adherence when grown at 30 degrees C . This finding may be of importance for exogenous infections, with Candida spp . invading the body from the outside, where the temperature is usually lower than the physiological body temperature. Mycopathologia, 1996, 136(1), 25 - 32 Onychomycosis in Rome, Italy; Mercantini R et al.; This report presents the results of a study conducted between 1985 and 1994 on onychomycosis observed in the city of Rome . Six thousand six hundred and eighty eight patients were examined during this period . Among them 1,762 (26.3%) were affected by fungal nail infections . Because the etiologic agents could not be isolated in 105 cases (6%), the results refer to 1,657 subjects (24.8% of the total), presenting with positive microscopic and cultural examinations . Thirty eight patients (2.3%) had onychomycosis of both their hands and feet . From an etiological point of view, 59.1% of the nail infections were caused by yeasts, 23.2% were infected with dermatophytes and 17.6% by non-dermatophytic fungi . The etiology of onychomycosis of the hands differed from that of the feet . Yeasts were primarily responsible for onychomycosis of the hands (86.2%), while dermatophytes caused tinea unguium peduum (48%) . Fungal fingernail infections by Candida spp . were the most common (50.3%), followed by those of the feet by dermatophytes (20%) . Candida albicans was responsible for 70.6% of the hand infections but for only 15.9% of those of the feet . Trichophyton rubrum and T mentagrophytes were the most common dermatophytes, mainly causing toenail infections (23.4% and 21%, respectively), while Aspergillus spp., Scopulariopsis brevicaulis, Acremonium spp . and Aspergillus niger were the most common non-dermatophytes observed . With regard to sex, the fungal nail infections were more widespread in women (72.1%) and in subjects of both sexes over the age of 50. Mycopathologia, 1996, 136(1), 17 - 20 Utility of Albicans ID plate for rapid identification of Candida albicans in clinical samples . Rapid identification of Candida albicans; Contreras I et al.; Albicans ID (bioMerieux, Marcy l'Etoile, France) is a ready-to-use medium that contains a chromogenic substrate that allows rapid detection and specific identification of Candida albicans . We have evaluated its clinical performance by culturing 846 clinical specimens from pregnant women and neonates . A 99.2% sensitivity and a 100% specificity were observed in the identification of C . albicans isolates from primary culture. Mycopathologia, 1996, 135(2), 103 - 8 Pulmonary clearance of Candida albicans: effect of exposure to native and metal-coated fly ash; Bajpai R et al.; The viability of Candida albicans was tested at various intervals in the lungs of rats following single intratracheal inoculation of the yeast cells . Most of the inoculated cells were cleared from lungs within 48 hr after exposure . Clearance was enhanced in lungs exposed to metal-coated fly ash than in those exposed to native fly ash . The validity of these studies was verified in vitro using peritoneal macrophages of mice exposed in vivo to native and metal-coated fly ash . An increase in phagocytic and intracellular killing of macrophages harvested from animals exposed to native or metal-coated fly ash was observed. Mycopathologia, 1996, 135(2), 85 - 8 Influence of fructose on Candida albicans germ tube production; Vidotto V et al.; The influence of different fructose concentrations (5, 3, 1 and 0 g/l) was tested on Germ Tube (GT) production by Candida albicans strain AS3P, using a Minimal Synthetic Medium (MSM) without (NH4)2SO4 . The results obtained showed good GT production in the presence of all the different fructose concentrations and in the absence of any nitrogen source . The greatest GT production was obtained with 3 g/l of fructose vs 1 g/l of glucose, after 4 hr of incubation . On the other hand fructose consumption was lower than that of glucose at all concentrations over the 4 hour period . The data obtained may suggest that fructose is metabolized in a different way from glucose for GT production by C . albicans. Mycopathologia, 1996, 135(2), 79 - 83 Inhibition of yeast-to-mycelium conversion of Candida albicans by conjugated styryl ketones; Manavathu E et al.; Candida albicans is a dimorphic pathogenic yeast capable of producing alternate morphological forms (yeast or mycelium) in response to environmental changes . The dimorphism of C . albicans plays an important role in the pathophysiology of this organism . The intracellular level of glutathione, which helps to maintain the oxidation-reduction potential of the cell, is decreased significantly during the yeast-to-mycelium conversion implicating the possible involvement of thiols in the yeast-to-mycelium transition . To evaluate the possible participation of sulphydryl group(s) containing component(s) in the yeast-to-mycelium transition of C . albicans, we examined the effect of a group of newly synthesized thiol-alkylators on the production of germ tubes from yeast cells . Several conjugated styryl ketones which are thiol-alkylators, and p-chloromercuriphenylsulphonate (a known nonpenetrating thiol-blocker) inhibited the yeast-to-mycelium conversion of C . albicans . The thiol-alkylators at 20 microM failed to inhibit four key enzymes (gamma-glutamyltranspeptidase, glutathione reductase, glutathione S-transferase and glutathione peroxidase) involved in glutathione utilization indicating that the inhibition of yeast-to-mycelium conversion is not mediated by the inhibition of glutathione metabolic enzymes . Moreover, these results suggest that a key thiol-blocker sensitive component(s) containing a critical sulphydryl group(s) is involved in the yeast-to-mycelium transition of C . albicans. Immunobiology, 1996, 196(4), 363 - 74 Tumor necrosis factor (TNF) induction from monocyte/macrophages by Candida species; Aybay C et al.; Candida albicans was studied for its capacity to induce TNF production from mouse peritoneal macrophages (PM phi) . TNF activities in the culture supernatants of Candida-stimulated PM phi and human peripheral blood monocytes were assessed by L 929 bioassay and ELISA respectively . C . albicans induced TNF production from PM phi and human peripheral blood monocytes in a dose-dependent manner . Although the capacity was lesser than live form, heat-killed C . albicans was also found to be capable of stimulating PM phi to induce TNF . The filtered supernatant of 24 h cultured live C . albicans had no effects on TNF production from PM phi . Saccharomyces cerevisiae-extracted mannan, a yeast cell wall antigen, induced TNF production from PM phi in a dose-dependent manner . Thus, the effect of C . albicans on TNF production from PM phi was seemed to be directly related to the presence of the yeast cell wall itself . Compatible with these data, when various candida species (C . albicans, C . tropicalis, C . pseudotropicalis . C . lusitaniae, C . krusei, C . parapsilosis, C . guilliermondii, C . stellatoidea, C . glabrata) and S . cerevisiae were compared to each other, at a concentration of 2 x 10(6) yeast cells/ml from each species, it was observed that TNF inducing capacities varied . Among the species used in this study, C . guilliermondii and C . glabrata, of which the yeast cell size were the smallest ones, were found to be less potent than that of others to induce TNF from PM phi. Skin Pharmacol, 1996, 9(6), 388 - 94 Antifungal activity of the essential oil of Melaleuca alternifolia (tea tree oil) against pathogenic fungi in vitro; Nenoff P et al.; The in vitro antifungal activity of tea oil, the essential oil of Melaleuca alternifolia, has been evaluated against 26 strains of various dermatophyte species, 54 yeasts, among them 32 strains of Candida albicans and other Candida sp . as well as 22 different Malassezia furfur strains . Minimum inhibitory concentrations (MIC) of tea tree oil were measured by agar dilution technique . Tea tree oil was found to be able to inhibit growth of all clinical fungal isolates . For the investigated dermatophytes MIC values from 1,112.5 to 4,450.0 micrograms/ml with a geometric mean of 1,431.5 micrograms/ml were demonstrated . Both C . albicans strains and the other strains belonging to the genus Candida and Trichosporon appeared to be slightly less susceptible to tea tree oil in vitro . However, their MIC values, which varied from 2,225.0 to 4,450.0 micrograms/ml (geometric mean 4,080 micrograms/ml), indicated moderate susceptibility to the essential oil of M . alternifolia . The lipophilic yeast M . furfur seemed to be most susceptible to tea tree oil . MIC values between 556.2 and 4,450.0 micrograms/ml (geometric mean 1,261.5 micrograms/ml) were found against the tested M . furfur strains . However, when calculated as percentage tea tree oil of the agar, the above-mentioned concentrations correspond to 0.5-0.44% tea tree oil content . These values are far below the usual relatively high therapeutic concentrations of the agent; approximately 5-10% solution or even the concentrated essential oil are used for external treatment . In comparison with tea tree oil, in vitro susceptibility against miconazole, an established topical antifungal, was tested . As expected, very low MIC values for miconazole were found for dermatophytes (geometric mean 0.2 microgram/ml), yeasts (geometric mean 1.0 microgram/ml), and M . furfur (geometric mean 2.34 micrograms/ml) . It is suggested that the in vivo effect of tea tree oil ointment in the therapy of fungal infections of the skin and mucous membranes as well as in the treatment of dandruff, a mild form of seborrheic dermatitis, may be at least partly due to an antifungal activity of tea tree oil. Microbios, 1996, 87(352), 161 - 7 A disc plate assay for characterization of the effect of interaction between polyenes and azoles on growth of Candida albicans CA12; Cao B et al.; A simple, reproducible and efficient assay was described for visual demonstration that triazole fluconazole interfered with the anti-Candida albicans activity of polyene amphotericin B . The assay also indicated the existence of more than one antifungal mechanism involving imidazole ketoconazole. J Biol Regul Homeost Agents, 1996 Jan-Mar, 10(1), 8 - 12 Mannoproteins from Candida albicans elicit a Th-type-1 cytokine profile in human Candida specific long-term T cell cultures; La Sala A et al.; Since T lymphocytes are active producers of regulatory cytokines, long-term T cell cultures (LTTC) specific for a major mannoproteic antigen (MP) of Candida albicans from peripheral blood mononuclear cells (PBMC) of healthy donors were generated and their cytokine profile studied . LTTC consisted of an expanded CD3CD4 T-helper (Th) populations, with a high proportion of CD45R0 T memory cells . Stimulation of LTTC by MP induced a Th-1 type cytokine profile, as indicated by the presence of IFN-gamma and the absence of IL-5 (both as mRNA and protein) in cell cultures and supernatants . These results suggest a predominant Th1 response elicited by C . albicans mannoprotein antigen in human PBMC. Wien Med Wochenschr, 1996, 146(13-14), 354 - 6 {Microbiological studies of a nasal positive pressure respirator with and without a humidifier system}; Hetzel J et al.; 13 patients with obstructive sleep apnea syndrome treated with CPAP-therapy and complicating affections of the nasal and pharyngeal mucosa were enrolled in a randomized cross-over study comparing therapy with a heated humidifier (HC 100, company Fisher & Paykel) and treatment with a heat and moisture exchanger (Typ I, company Dahlhausen) . We assessed the bacterial and fungal colonisation of the nasal masks of all patients . Samples of mask rinses were taken after the two treatment periods (2 weeks each) and the period without humidification in between . All microbes were found to have pathological potency . There was no significant difference in the total concentration of the microbes in the different treatment modalities . In a few cases however, gram negative bacteria were detected on the masks during humidification with a heated humidifier, but not with heat and moisture exchangers . Legionella spec . were not detectable in any of the samples . Candida albicans was the only fungus detectable . No patient had any infection of the upper or lower respiratory system associated with humidification therapy. Biotherapy, 1996, 9(1-3), 175 - 85 In vitro studies during long-term oral administration of specific transfer factor; Pizza G et al.; 153 patients suffering from recurrent pathologies, i.e . viral infections (keratitis, keratouveitis, genital and labial herpes) uveitis, cystitis, and candidiasis were treated with in vitro produced transfer factor (TF) specific for HSV-1/2, CMV and Candida albicans . The cell-mediated immunity of seropositive patients to HSV-1/2 and/or CMV viruses was assessed using the leucocyte migration inhibition test (LMT) and lymphocyte stimulation test (LST) in presence of the corresponding antigens, and the frequency of positive tests before, during and after TF administration was studied . The data were stratified per type of test, antigen and the recipients' pathology, and statistically evaluated . For the LMT, a total of 960 tests were carried out for each antigen dilution, 3 different antigen dilutions were used per test . 240/960 tests (25.4%) were found positive during non-treatment or treatment with unspecific TF, whereas 147/346 tests (42.5%) were found positive when the antigen corresponding to the specificity of the TF administered to the patient was used (P < 0.001) . When the data were stratified following pathology, a significant increased incidence of positive tests during specific treatment was also observed (0.0001 < P < 0.05) . In the LST (1174 tests), a significant increase of thymidine uptake was observed in the absence of antigen (control cultures), during treatment with both specific and unspecific TF, but also in the presence of antigen and/or autologous serum during specific TF administration (P < 0.0001) . TF administration also significantly increased the soluble HLA class I antigens level in 40 patients studied to this effect. Biotherapy, 1996, 9(1-3), 97 - 103 Transfer factor in chronic mucocutaneous candidiasis; Masi M et al.; Fifteen patients suffering from chronic mucocutaneous candidiasis were treated with an in vitro produced TF specific for Candida albicans antigens and/or with TF extracted from pooled buffy coats of blood donors . CMI of the patients was assessed using the LMT and the LST in presence of candidine . The aim of the study was the clinical evaluation of TF treatment and the incidence of positive tests before, during, and after therapy . Immunological data were matched using the Chi square test . 87 LMT were performed for each antigen dose and at the dilution of 1/50, 58.9% (33/56) tests were positive during non-treatment or non-specific TF treatment . On the contrary 83.9% (26/31) were positive during specific TF treatment (P < 0.05) . In the LST, a significant decrease of thymidine uptake in the control cultures in presence of autologous or AB serum was observed when patients were matched according to non-treatment, and both non specific (P < 0.05) and specific TF treatment (P < 0.01) . Only during specific TF treatment was a significant increase of reactivity against the Candida antigen at the highest concentration noticed, when compared with the period of non specific treatment (P < 0.01) . Clinical observations were encouraging: all but one patient experienced significant improvement during treatment with specific TF . These data confirm that orally administered specific TF, extracted from induced lymphoblastoid cell-lines, increases the incidence of reactivity against Candida antigens in the LMT . LST reactivity appeared not significantly increased with respect to the periods of non treatment, but was significantly increased when it was compared to the non-specific TF treatment periods . At the same time, a clinical improvement was noticed. Diagn Microbiol Infect Dis, 1996 Jan, 24(1), 31 - 5 Comparison of the Murex Candida albicans CA50 test with germ tube production for identification of C . albicans; Fenn JP et al.; A total of 502 yeast isolates were tested with the 30-min MUREX Candida albicans CA50 (Norcross, GA) test for presumptive identification of C . albicans . The results were compared with the standard 2-h germ tube test, which was the reference standard . Of the 502 isolates, 316 were C . albicans and 186 were non-C . albicans . Identifications were based on germ tube reactions; the API20C and chlamydospore agars were used when discrepant results persisted between the germ tube and MUREX test after repeat testing of the MUREX method . A total of 16 C . albicans gave negative results on initial testing with the MUREX test but were interpreted as positive when repeated . Three germ tube negative yeasts initially tested positive with the MUREX but were negative when repeated . Two additional yeast isolates gave incorrect results with the MUREX, even with repeat testing: C . albicans and C . lusitaniae . The initial sensitivity and specificity for the MUREX C . albicans CA50 test were 94.6% and 97.8%, respectively . As an addition to the study, two fetal bovine sera were compared for production of germ tubes; fetal bovine serum and Fetal Clone II . The testing found them to be in 100% agreement. Microbiol Immunol, 1996, 40(11), 821 - 5 Cooperative anti-Candida effects of lactoferrin or its peptides in combination with azole antifungal agents; Wakabayashi H et al.; The effects of lactoferrin (LF), an antimicrobial protein secreted in body fluids, and its peptides in combination with azole antifungal agents were investigated by the micro-broth-dilution method in a study of Candida albicans . In the case of LF, its pepsin hydrolysate (LFhyd) or the LF-derived antimicrobial peptide Lactoferricin B (LF-B), the concentrations required to inhibit the growth of Candida decreased in the presence of relatively low concentrations of clotrimazole (CTZ) . The minimum inhibitory concentration (MIC) of all azole antifungal agents tested was reduced by 1/4-1/16 in the presence of a sub-MIC level of each of these LF-related substances . Polyene and fluoropyrimidine antifungal agents did not show such a combined effect with these LF-related substances . The anti-Candida activity of LF or LF-B in combination with CTZ was shown to be synergistic by checkerboard analysis . These results indicate that LF-related substances function cooperatively with azole antifungal agents against C . albicans. Mycopathologia, 1996, 134(2), 75 - 82 Candida biotypes in patients with oral leukoplakia and lichen planus . Candida biotypes in leukoplakia and lichen planus; Lipperheide V et al.; Prevalence of yeasts in 35 leukoplakia and 34 oral lichen planus patients was compared with that observed in persons without oral diseases . Serotype and morphotype were determined on Candida albicans isolates . Yeasts were isolated from the oral cavity specimens of 43.7% of the patients . C . albicans (serotype A) was the predominant species (76% in leukoplakia, 88.2% in lichen planus and 60.8% in healthy persons) . Sixteen morphotypes were encountered on malt extract agar, being 732, 733, 734, 753 and 754 the most frequently found . Morphotypes SP1N and SP1Y were the most common on Sabouraud-trypheniltetrazolium agar (68.4% of the isolates from leukoplakia and 73.3% from lichen planus, but only 46.6% of the isolates from healthy oral mucosa showed SP1N morphotype) . Presence of oral lesions was associated with a marked reduction in the yeast species and C . albicans biotypes, suggesting that C . albicans and particularly some of its biotypes, show a high potential of adaptation to the changes associated with the development of oral leukoplakia and lichen planus. Rev Laryngol Otol Rhinol (Bord), 1996, 117(2), 119 - 21 {A study of otomycoses in Yaoundé}; Lohoue Petmy J et al.; The authors report the results of a six-month evaluation of otomycoses in the ENT Department of CHU and the Central Hospital of Yaounde . We examined 2 592 patients of both sexes presenting with ear affections . The prevalence of Otomycoses is 6,09% . This is an adult problem with both sexes equally affected . Clinically the main symptoms were burning sensation in the ears, pruritus, sensation of fullness in the ear, hypoacousia and otorrhea . Clinical lesions are of many types including myringitis, tympanic perforation and otitis externa . The fungi responsible for these affections are mainly Aspergillus fumigatus (56,16%) for the Aaspergillus and Candida albicans (48,38%) for yeasts . The other species are Aspergillus niger, Aspergillus flavus, C . Krusei, C . pseudotropicalis, C . Tropicalis, Geotrichum candium and Torulopsis glabrata. Scand J Infect Dis, 1996, 28(5), 503 - 6 Postantifungal effect and effects of low concentrations of amphotericin B and fluconazole on previously treated Candida albicans; Minguez F et al.; The objective of the study was to assess (a) the postantifungal effect (PAFE) of amphotericin B (AmB) and fluconazole (Flu) on two Candida albicans strains, and (b) the effect of low concentrations of AmB or Flu on yeasts previously exposed to AmB or Flu, respectively, in the presence or absence of 10% human serum . In the absence of serum, AmB exerted a positive effect (at 0.5-5.0 h) depending on the concentration and the strain used . Flu, however, produced negative effects (at -1.2 to -0.1 h) . When the experiment was conducted in the presence of serum, the duration of all PAFEs increased significantly, especially those induced by Flu that became positive . Pretreated yeasts were more susceptible than untreated controls to the antifungal activity of low concentrations of the drugs . Growth delay was more pronounced with Flu (up to 5.2 h), whereas the greatest decrease in log10 at 12 h was slightly more pronounced for AmB . A knowledge of PAFEs and the effects of low drug concentrations on pretreated yeasts and the effects of serum on these is important in order to gain more insight into the in vivo activity of the study drugs. Nippon Ronen Igakkai Zasshi, 1996 Jan, 33(1), 33 - 7 {Two cases of Candida endocarditis associated with abdominal disease}; Hamada Y et al.; Two cases of Candida endocarditis are reported . The first case was of a 63-year-old man who had a positive blood culture for Candida albicans during treatment for liver abscess and early gastric cancer . He was transferred to our department, and aortic and tricuspid regurgitation due to Candida endocarditis was diagnosed . The patient was successfully treated with aortic valve replacement, tricuspid valve plasty and anti-fungal agents . The second case was of a 65-year-old man who complained of fever . Despite a diagnosis of common bile duct cancer and resection of the tumor, the fever persisted . He was transferred to our department and was diagnosed having aortic regurgitation due to Candida endocarditis, complicated by heart failure . Although intense medical therapy including antifungal agents, diuretics, catecholamines and digoxin was initiated, the patient died from multiple embolisms 9 days later . In the treatment of Candida endocarditis, early diagnosis and early decision-making for either surgical or medical therapy is indispensable . Although the prevalence of Candida endocarditis is low, the differentiation of this disease should be taken into account in febrile elderly patients with long-standing therapy with antibiotics. Microbiol Immunol, 1996, 40(2), 125 - 31 Kinetics of anti-mannan antibodies useful in confirming invasive candidiasis in immunocompromised patients; van Deventer AJ et al.; In studying the anti-mannan antibodies longitudinally in serial serum samples of three immunocompromised patients, it was observed that anti-mannan antibodies started to increase shortly after the moment that cultures of deep-tissue sites became positive with Candida albicans . The mean anti-mannan antibody titers determined in a group of 36 immunocompromised patients with invasive candidiasis increased within two weeks after the probable onset of invasive candidiasis . In contrast, anti-mannan antibody levels in serial serum samples of 14 immunocompromised patients who were only colonized with C . albicans remained stable or decreased over time . The HA test measuring the anti-mannan antibodies was 64% sensitive and 89% specific in determining invasive candidiasis . In contrast, antibodies specific for candidal cytoplasmic antigens or enolase alone were of little value in confirming invasive candidiasis in these immunocompromised patients. Microbiol Immunol, 1996, 40(7), 473 - 9 Effect of macrolide antibiotics on macrophage functions; Xu G et al.; Macrolide antibiotics have a variety of actions other than antimicrobial activities . Recently, it has been suggested that macrolide antibiotics act as immunomodulators . In this study, we evaluated the effects of macrolide antibiotics on macrophage functions . For the macrophage, we used the mouse macrophage cell line J774.1 . The following effects of macrolide antibiotics on macrophage functions were evaluated: the effect of macrolide antibiotics on macrophage growth; the phagocytosis of beads; cytocidal activity against Candida albicans; and chemotaxis to lipopolysaccharide (LPS) . Macrolide antibiotics except for azithromycin significantly stimulated the growth of the macrophage . In addition, pretreatment with macrolide antibiotics except for roxithromycin significantly stimulated the macrophage phagocytosis of beads, macrophage chemotaxis to LPS, and macrophage cytocidal activity against Candida albicans . These results suggest that macrolide antibiotics stimulate macrophage functions. Infection, 1996 Jan-Feb, 24(1), 17 - 21 Fungal endocarditis--a report on seven cases and a brief review; Hogevik H et al.; Candida endocarditis is an unusual but severe complication of systemic infection caused by Candida albicans and occasionally by other fungal species . We describe seven cases that occurred during a period of 20 years in western Sweden . In four cases infections were located on prosthetic valves and in three cases native valves were involved . Three patients died of the disease in the acute phase . A definite diagnosis was established in one of four survivors . This patient had an aortic valve endocarditis and a saddle embolisation and was treated with immediate surgery, followed by intensive treatment with liposomal amphotericin B+ flucytosine . Fungal endocarditis is still a serious disease with a high mortality and whenever the diagnosis is suspected, antifungal therapy must be started and transesophageal sonography should be performed to visualize vegetations . Immediate surgery should be considered. J Clin Lab Anal, 1996, 10(2), 59 - 69 Evaluation of an optimized system for random amplified polymorphic DNA (RAPD)-analysis for genotypic mapping of Candida albicans strains; Holmberg K et al.; A simple, rapid, and cost-effective protocol has been developed for a PCR-based molecular typing method for Candida albicans, which includes the use of a commercially available medium (Chelex 100 Resin) for DNA extraction and a single set of two arbitrarily chosen oligonucleotide (10 nt length) primers for random amplified DNA(RAPD)-analysis . The optimized parameters for the amplification components and conditions for the selected primer combination have been determined to avoid artifactual variation (absence/presence of bands) in RAPD banding patterns in repeated assays . The optimized RAPD-assay consistently generated DNA-patterns of 33 genetically unrelated C . albicans isolates that contained ten polymorphic markers in the non-artifactual banding patterns . The intralaboratory reproducibility of RAPD patterns was efficient and consistent provided the optimized amplification conditions were rigidly controlled . Interlaboratory reproducibility was tempered by slight variations in time of cyclers of different thermocyclers . In comparison, the RAPD assay was almost equal to restriction enzyme analysis (REA) (Eco RI digested chromosomal DNA) in discrimination, and the RAPD assay was able to group isolates of C . albicans that were untypable by REA . The protocol outlined for an optimized RAPD-assay of C . albicans has the potential to be widely useful epidemiological screening tool that can be easily applied in the clinical laboratory. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 1996 Jan, 81(1), 44 - 9 Use of a microtiter plate assay to detect the rate of killing of adherent Candida albicans by antifungal agents; Hamers AD et al.; OBJECTIVES: Candida albicans may become adherent to prosthetic devices of various kinds and thereby produce infections that are difficult to treat with standard antifungal therapy . The objective of the present work was to study the effectiveness of antifungal agents against adherent C . albicans yeast cells . STUDY DESIGN: A microtiter plate assay was developed to assess the time required for killing of the fungal cells by three antifungal agents . RESULTS: The assay initially was validated by demonstrating that the percentage of organisms adhering to the test wells was relatively constant and that exposure to the antifungal agents caused only minimal dislodgement of viable organisms from the plates . In studies that used this assay to determine the time required for killing the adherent yeast cells, chlorhexidine was found to be the most effective; in fact, in comparing the minimal lethal concentrations of the agents for exposures of 2 minutes versus 4 hours, a ratio of 2.9 was obtained for chlorhexidine versus 1050 for amphotericin B and 556 for nystatin . CONCLUSION: The microtiter plate assay used in these studies may therefore be useful as a screening test to determine which antifungal agents have the most rapid fungicidal effects on adherent fungal organisms. Clin Infect Dis, 1996 Jan, 22(1), 133 - 5 Pulmonary mycetoma due to Candida albicans: case report and review; Shelly MA et al.; A pulmonary mycetoma is a round to oval-shaped mass of fungi situated within a cavity in the lung . Most mycetomas are caused by Aspergillus species . Other fungi have occasionally been reported to cause clinically and roentgenographically similar lesions . We report a case of pulmonary mycetoma caused by Candida albicans . Review of the literature suggests that pulmonary mycetoma due to this species is uncommon, and when it has been suspected, specific documentation has been lacking. Gynecol Obstet Invest, 1996, 41(1), 30 - 4 Candida albicans: is it associated with nipple pain in lactating women? Amir LH, Garland SM, Dennerstein L, Farish SJ. Persistent nipple pain in lactating women, burning in nature, and associated with radiating breast pain, has been claimed by some authorities to be due to 'thrush' (candida) infection . Yet, scientific proof has been lacking . This study compared microbiological assessment of 61 women with nipple pain, 64 women without nipple pain, and 31 non-lactating women . Swabs of the nipple and baby's mouth, and expressed breast milk were collected for culture . Growth of Candida albicans (nipple and milk) was found more often in the women with nipple pain (19%) than in the control group (3%, p < 0.01) . In addition, Staphylococcus aureus was also associated with nipple pain (p < 0.0001), and independently associated with nipple fissures (p < 0.0001) . Neither C . albicans nor S . aureus was found on the nipples of the non-lactating group. Mycopathologia, 1996, 134(1), 13 - 20 Common and form-specific cell wall antigens of Candida albicans as released by chemical and enzymatic treatments; Lopez-Ribot JL et al.; In order to investigate the antigenic properties of the proteins and mannoproteins present in the cell surface of Candida albicans, and to identify individual antigenic moieties and their distribution, a number of polyclonal antisera were obtained by immunizing rabbits with chemical and enzymatic cell wall extracts obtained from intact cells from both growth forms (yeast and mycelium) of the fungus . Prior to injection, wall moieties present in the extracts were subjected to different treatments and/or purification procedures such as adsorption onto polystyrenelatex microbeads or electrophoretic separation . When used as probes in indirect immunofluorescence assays, the different antisera gave rise to different fluorescence patterns varying in intensity and topological localization of the reactivity in C . albicans cells . When the different antisera were used as probes in Western blots of wall proteinaceous materials solubilized from both blastospores and germ tubes, differences in reactivity and specificity were readily discernible, allowing to identify a number of common and form-specific cell wall components . Of special interest was the fact that one of the antisera raised, after adsorption onto heat-killed blastospores, specifically recognized medium to low molecular weight moieties present only in the cell wall extracts from germ tubes . When this antiserum was used as probe in immunofluorescence assays, reactivity was confined to the hyphal extensions . Together, these observations seem to indicate that the different antibody preparations described in this report could represent important tools in the study of different aspects of the cell wall biology in C . albicans, including the identification and study of the distribution of common and form-specific cell wall-bound antigens. Mycopathologia, 1996, 134(1), 1 - 6 Re-expression by Candida albicans germ tubes of antigens lost during subculture of blastospores; Hernando FL et al.; The effect of germ tube induction on the antigenic variability in C.albicans was studied in strains from blood cultures (Group I) and superficial candidiasis (Group II) . When compared by immunoblotting with a rabbit antiserum, antigenic extracts from Group I strains grown as blastospores showed a higher reactivity than that of Group II strains . Major bands in Group I strains (45-47, 33, 30 kDa) were continuously expressed through the subcultures in vitro but, with the exception of the 45 kDa band, the reactivity of all of them decreased or disappeared after the tenth subculture in Group II strains . The induction of the germ tubes produced the re-expression of the antigens lost during subculture in the yeast form, the effect being very clear in Group II strains . The re-expression by C . albicans germ tubes of antigens lost during subculture of blastospores in vitro and the higher reactivity shown by Group I strains grown in mycelial phase should be taken into consideration when a test to detect anti-C . albicans antibodies is to be developed. Mycopathologia, 1996, 133(3), 143 - 7 Glucose influence on germ tube production in Candida albicans; Vidotto V et al.; The influence of different glucose concentrations was tested in minimal synthetic medium on Candida albicans strain . After 18 hours of starvation, germ-tube (GT) production, amount of consumed glucose, oxygen and the pH of the medium were checked every hour from the beginning through the end of the experiment . Optimal GT production was obtained with 1 g/l of glucose . At this concentration the greatest glucose and oxygen consumption were also noted . No pH variations in the medium were observed in all of the glucose concentrations used . At 3 and 5 g/l glucose concentrations a lower GT production were obtained . The Crab-tree effect might interfere with GT production when glucose concentration is higher than 1 g/l . This data may support the hypothesis that GT production is strictly glucose dependent. Acta Microbiol Immunol Hung, 1996, 43(1), 47 - 53 Characteristics of Streptomyces strains isolated from soils in two landfill areas in north Jordan; Abussaud MJ; A total of 114 Streptomyces strains were isolated and purified from soils collected from Al Akider (53) and from Al Kafeer (61) landfill areas in north Jordan . The Al Akider strains were classified into 5 colour series gray (27), white (18), yellow (3), violet (3) and green (2); while the Al Kafeer strains were classified into 6 colour series white (26), gray (16), yellow (9), red (2), green (7) and blue (1) . Melanin pigment was produced by 21 and 25% of the Al Akider and Al Kafeer strains, respectively, while soluble pigment was produced by 15% of the A; Akider and 21% of the Al Kafeer strains; 17% of Al Akider strains and 23% of Al Kafeer strains showed distinctive reverse side pigment . Forty, 32, 19, and 9% of the Al Akider strains had spiral, rectus, flexous and retinaculum apertum spore-chains, respectively, while the distribution of the Al Kafeer strains in the same spore-chain forms was equally 25% each . Arabinose, xylose, inositol, fructose, rhamnose, sucrose, raffinose, and mannitol were utilized by 91, 53, 89, 60, 30, 25 and 79% of the Al Akider strains and by 84, 59, 62, 64, 70, 75, 41 and 26% of the Al Kafeer strains, respectively, while only 2% of the Al Kafeer strains were found to utilize cellulose . Thirty-six percent of the Al Akider strains showed, in vitro activity against Staphylococcus aureus followed by Aspergillus niger (26%), Bacillus cereus and Saccharomyces cerevisiae (25% each), Fusarium monilliforme (21%), Candida albicans (15%), Escherichia coli (8%) and Pseudomonas aeruginosa (4%), while 51, 49, 46, 34, 25, 15, 7 and 2% of the Al Kafeer strains exhibited activity against A . niger, S . cerevisiae, B . cereus, S . aureus, F . monilliforme, C . albicans, P . aeruginosa and E . coli, respectively. Peptides, 1996, 17(2), 219 - 24 Modulation of murine peritoneal macrophage functions by gastrin; de la Fuente M et al.; The effect in vitro of gastrin-17 and gastrin-34 was studied at concentrations from 10(-12) to 10(-6) M on several functions of resting peritoneal macrophages from BALB/c mice: adherence to substrate, mobility (spontaneous and directed by chemical gradient or chemotaxis), and ingestion of inert particles (latex beads) or cells (Candida albicans) . Both gastrins, at concentrations from 10(-10) to 10(-8) M, inhibited significantly all functions studied with the exception of adherence, which was increased . A dose-response relationship was observed, with a maximum inhibition of macrophage functions found at 10(-9) M . These peptides induced in murine macrophages a significant increase of cAMP levels at 60 and 120 s . Adenosine, an adenylate cyclase inhibitor, significantly increased the ingestion of latex beads, whereas the combined presence of adenosine and either G-17 or G-34 produced similar values to those of control samples without adenosine or gastrin . These results suggest that gastrin is a negative modulator of several macrophage functions, and that the inhibition of these activities is carried out through an increase of intracellular cAMP levels. Infect Control Hosp Epidemiol, 1996 Jan, 17(1), 47 - 52 The epidemiology of colonization; Jarvis WR; Colonization is the presence of a microorganism in or on a host, with growth and multiplication but without any overt clinical expression or detected immune response in the host at the time it is isolated . Normal colonization in humans begins during the birth process and through subsequent contacts with the inanimate or animate environments until a delicately balanced "normal" flora is established; subsequently, the precise components of this flora evolve . This normal flora, such as coagulase-negative Staphylococcus or Staphylococcus aureus on the skin or Candida albicans in the gastrointestinal tract, vagina, or perineal area, can result in infection when normal body defenses are impaired through underlying disease, immunomodulating therapy, or the use of invasive devices, or when the delicate balance of the normal flora is altered through antimicrobial therapy . Many, if not most, hospital-acquired infections result directly or indirectly from patient colonization; studies have shown that hospitalized patients are colonized rapidly with hospital flora . Recognizing this reservoir of patients colonized with epidemiologically important pathogens in our hospitals and improving barrier precaution measures or altering host susceptibility will be necessary if we are to reduce the incidence of infections with these organisms. Behav Brain Res, 1996, 73(1-2), 369 - 74 Effect of d-fenfluramine on the local immune response to the opportunistic microbial pathogen Candida albicans; Mathews HL et al.; In this study the effects of systemic administration of d-fenfluramine on the local lymphocyte response to Candida albicans was evaluated . Experimental animals were challenged intradermally with Candida albicans and then administered d-fenfluramine (d-FEN 1 mg/kg per day, i.p.) or a balanced salts solution . At successive time intervals, lymphocytes were derived from the draining lymph nodes and from the dermal sites of active microbial challenge . A CD8+ lymphocytosis was observed in all animals challenged with Candida albicans . The CD8+ lymphocytosis was augmented in animals that received d-FEN . Phenotypically, lymph nodes from d-FEN treated animals showed a marked increase in CD3+ and CD8+ lymphocytes, a modest increase in the numbers of NK1.1+ cells and a decrease in Ig+ lymphocytes . Functionally, lymphocytes from the site of active microbial challenge were capable of direct growth inhibition of Candida albicans . The anti-fungal activity was augmented in the animals that received d-FEN . These results suggest that d-FEN augments the local T lymphocyte response to an important microbial pathogen by increasing the number of T lymphocytes draining the site of microbial infection and by increasing the biological activity of the lymphocytes at the site of the infection. Antimicrob Agents Chemother, 1996 Jan, 40(1), 263 - 6 Comparison of fluconazole and amphotericin B for treatment of experimental Candida albicans endocarditis in rabbits; Chemlal K et al.; Amphotericin B (AmB) and fluconazole, administered intraperitoneally for 7 days, were compared in a rabbit model for Candida albicans endocarditis . When given early, AmB was more effective than fluconazole for reducing CFU counts in vegetations (P < 0.01) and kidneys . Forty-eight hours after the last dose, AmB was still detected in all vegetations whereas fluconazole was detected in only one case. Mycoses, 1996 Jan-Feb, 39(1-2), 45 - 50 Fungicidal effect of tyrothricin on Candida albicans; Kretschmar M et al.; Tyrothricin, a polypeptide antibiotic, is active against yeast cells . Tyrothricin was rapidly fungicidal towards Candida albicans . Concentration of four times the minimum inhibitory (25 mg l-1) reduced the yeast numbers by more than 3 log10 within 1 h . Similar results were obtained in a flow cytometric antifungal activity assay using the new two-colour probe for yeast viability, FUN-1, which measures impairment of metabolic activity . The respiratory activity of Candida albicans, measured in a XTT kinetic assay, was significantly reduced in comparison with controls by 3.12 mg l-1 of the substance . Because fungicidal concentrations of tyrothricin are locally achievable in patients, an evaluation of the local effect of tyrothricin in patients suffering from mucosal infections with Candida species should be considered. J Med Vet Mycol, 1996 Jan-Feb, 34(1), 57 - 61 Presence of multiple laminin- and fibronectin-binding proteins in cell wall extract of Candida albicans: influence of dialysis; Glee PM et al.; Candida albicans has been reported to express only one to three proteins that bind extracellular matrix proteins, such as laminin and fibrinogen . In those reports, cell wall extracts were subjected to various processing steps, such as dialysis and lyophilization, prior to Western blot analysis . Here, we demonstrate that dialysis for only 2 h of cell wall protein extracts results in a substantial loss (40-60%) of protein . With overnight dialysis, the loss was increased further . After 2 h of dialysis, wall extracts contained fewer laminin- and fibronectin-reactive proteins . In addition, the number of wall proteins in the extracts detected by a polyclonal anti-human fibronectin receptor antiserum decreased after dialysis . These results demonstrate that the C . albicans yeast cell wall contains multiple proteins capable of binding laminin and fibronectin and many of these proteins are not functionally detectable following dialysis. J Med Vet Mycol, 1996 Jan-Feb, 34(1), 11 - 7 Alveolar macrophage response to yeasts and inert particles; Nyberg K et al.; Interactions between alveolar macrophages (AM) from rats and a yeast with relatively high pathogenicity (Candida albicans), a yeast with low pathogenicity (Saccharomyces cerevisiae) and an inert control particle (amorphous silica) of similar diameters, 3-4 microns, were studied . Both yeasts were phagocytized significantly faster by AM than were the control particles and C . albicans significantly faster than S . cerevisiae . Quantitative nitroblue tetrazolium reduction by AM reflecting their oxidative metabolism was markedly increased in response to both fungi during the period of phagocytosis as well as 24 h after the phagocytosis . Macrophages with silica particles also showed a moderate but significant increase in oxidative metabolism 24 h after phagocytosis . Phagolysosomal pH was significantly higher for S . cerevisiae than the control particles after 3 and 24 h . pH in phagolysosomes with C . albicans tended to be higher after 3 h but was significantly lower after 24 h than in the phagolysosomes with silica particles . Both yeasts showed a considerable number (around 10%) of phagolysosomes with high pH > or = 6.5 after 3 h and a smaller percentage after 24 h . No such fraction could be seen for the control particles . Electron microscopy showed narrow passages from AM cell surface to phagolysosomes with particles . These passages might be more frequent in AM containing the yeasts and could explain the phagolysosomes with high pH. J Ethnopharmacol, 1996 Jan, 50(1), 55 - 9 Antimicrobial activity of Guinea-Bissau traditional remedies; Silva O et al.; The ethanolic extracts of twelve plants selected through ethnomedical survey in Guinea-Bissau were investigated for their in vitro antimicrobial properties over ten bacteria and Candida albicans, using agar diffusion and dilution methods . All the tested extracts showed some activity against at least one of the bacteria . Most of the extracts (79%) showed activity against Staphylococcus aureus and only one (Cryptolepis sanguinolenta) against Escherichia coli . Cryptolepis sanguinolenta and Terminalia macroptera root extracts showed some activity against Candida albicans as well as showing an interesting profile of activity against most of the enteropathogen microorganisms . Inhibition zones against Staphylococcus aureus were localised on extract chromatograms by bioautographic techniques. Klin Lab Diagn, 1996 Jan-Feb, (1), 30 - 2 {Infections of a fungal etiology in the cancer clinic}; Smolianskaia AZ et al.; Candida fungi, more than half of which are Candida albicans, are responsible for up to 28% of microflora contaminating the pathological material during infectious processes coursing in cancer patients . They may be isolated as a monoculture or in associations with bacteria, depending on the localization of the process . In both cases their pathogenetic significance is really great, which is confirmed by the efficacy of antimycotic therapy and prophylactic measures . The prevalence of fungal infections necessitates taxonomic identification of the isolated fungal cultures. Mycoses, 1996, 39 Suppl 1, 87 - 93 {LILAs (lipid-like leukocyte activators) isolated from Saccharomyces cerevisiae induce calcium mobilization in human neutrophilic granulocytes{}; Bulow M et al.; Recently, we isolated some new and functionally identical panchemotactic factors (Lipid-like leucocyte activators = LILAs) from Candida albicans, Saccharomyces cerevisiae and various dermatophytes, which are chemotactic for human neutrophilic and eosinophilic granulocytes as well as for monocytes . In order to answer the question, whether human neutrophilic granulocytes express a specific receptor for LILA, we now investigated the mobilisation of the intracellular second messenger calcium within human neutrophils which were stimulated with LILA . Furthermore, LILA-mediated activation of neutrophils was subjected to desensitisation experiments with the well known neutrophil activators 5-oxo-eicosatetraenoic acid, leukotriene B4, platelet activating factor, C5a, Interleukin-8, and N-for-myl-methionyl-leucyl-phenylalanin (FMLP) . The intracellular calcium concentration was measured by use of the fluorescence indicator FURA-2/AM . As a result we were able to show a significant dose-dependent increase in the intracellular calcium concentration after stimulation of human neutrophils with LILA . The desensitisation experiments revealed no cross-desensitisation between LILA and the well known stimuli . Our results show that LILA induces an intracellular calcium signal in addition to its panchemotactic activities . Therefore, calcium may act as second messenger in LILA-stimulated activation of neutrophils . Since LILA-mediated activation was maintained in the desensitisation experiments, LILA-specific receptors may be present on human neutrophils. Mycoses, 1996, 39 Suppl 1, 30 - 2 {Mycophobia--a new disease?}; Seebacher C; In the recent 18 months we analysed 13 patients with so-called therapy-resistant intestinal candidosis . Symptoms like flatulence, digestive trouble, intestinal inefficiency, arthralgia, heart trouble, etc., were declared . From four patients Candida albicans and in further three patients C . parapsilosis, C . lusitaniae, Trichosporon cutaneum, and Geotrichum candidum could be isolated . Serological tests were normal . In none of the 13 patients a mycosis which needed therapy was proven . Eight patients had signs of a depression or neurosis . In all 13 patients the occasional or repeated isolation of yeasts from faeces or the oral cavity was falsely interpreted as a fungal infection and thus became the inductor of a phobia. Acta Otorhinolaryngol Belg, 1996, 50(2), 137 - 42 Invasive fungal sinusitis in immunosuppressed patients . Report of three cases; Zapater E et al.; Report of three cases . Newly appeared immunosuppression related conditions have led to an increase in morbidity of systemic opportunistic mycoses . Rhinosinusal infection has also increased in frequency . Three invasive nasosinusal mycoses are presented: two cases of mucormycosis and a simultaneous infection by mucormycosis and candida albicans . In all cases, and despite treatment, progression of the disease could not be stopped and the patients died . The main characteristics of invasive nasosinusal mycoses are reviewed, to obtain early diagnosis . Early therapy improves the prognosis, and thus clinical suspicion justifies treatment before establishing a microbiological diagnosis. Ann Dermatol Venereol, 1996, 123(2), 85 - 9 {Oropharyngeal candidiasis resistant to fluconazole in patients infected by HIV}; Drobacheff C et al.; PURPOSE: To study the susceptibility to fluconazole of Candida albicans strains in oral candidiasis of HIV positive patients . PATIENTS AND METHODS: Eleven HIV positive patients with confirmed oral candidiasis were included in a 4 to 10 months prospective study . In addition, 23 HIV positive patients were evaluated in a restrospective study (14 with oral candidiasis and 9 control subjects) . The MICs to fluconazole of C . albicans were characterized by genotyping (electrophoretic karyotype) . RESULTS: Thirty patients were evaluable . Oral candidiasis was found in 21 patients; 7/21 patients (33,3 p . 100) developed resistant C . albicans strain (MIC > 32 mg/ml) after a mean fluconazole cumulative dose of 18 g . In this study, the electrophoretic karyotype confirmed the persistence of the same C . albicans strain in each patient . In addition increased colonization by C . krusei or C . glabrata was found in 6/21 patients (28.5 p . 100) . DISCUSSION: Our data demonstrate that prolonged treatment with fluconazole dose higher than 13 g induces the emergence of resistant C . albicans with persistence of the same C . albicans strain . Fluconazole has to be reserved to oral candidiasis after failure of a local treatment or to severe cases. Mycopathologia, 1996, 133(2), 89 - 94 Candida albicans stress mannoproteins expression in superficial and systemic candidiasis . Stress mannoproteins in Candida albicans; Ponton J et al.; The presence of heat shock mannoproteins (HSMPs) reactive with sIgA was demonstrated in several C . albicans strains . The subculture of the C . albicans isolated from mucosal surfaces on Sabouraud's dextrose agar at 25 degrees C switched off the HSMP expression . A re-expression of the HSMPs was obtained in the same medium by shifting the temperature of incubation to 37 degrees C . However, expression of HSMPs in two strains isolated from deep infections was maintained during several subcultures on Sabouraud's dextrose agar at 25 degrees C . A glycoprotein of 200 kDa seemed to be the main HSMP reacting with vaginal sIgA . The data presented in this study suggest that factors other than temperature can influence the expression of C . albicans HSMPs and therefore these antigens should be referred as stress mannoproteins. Mycopathologia, 1996, 133(2), 79 - 83 Isolation of opportunistic fungi from bronchoalveolar lavage of compromised hosts in Isfahan, Iran; Shadzi S et al.; In this study, bronchoalveolar lavage (BAL) specimens from 247 immunocompromised patients were investigated for the incidence of opportunistic fungi . In the direct examination and culture of the specimens, 5 (2.02%) of filamentous fungi and 55 (22.26%) yeasts were isolated and identified as follows: Aspergillus fumigatus (2), A . terreus (1), A . nidulans (1), Mucor sp . (1), Candida albicans (29), C . glabrata (3), C . Parapsilosis (1), Trichosporon beigelii (1), Candida sp . (13) and unknown yeasts (8) . In addition, one strain of Nocardia asteroides and two strains of Streptomyces sp . were isolated. Transpl Int, 1996, 9(1), 62 - 7 The impact of midline versus transverse incisions on wound complications and outcome in simultaneous pancreas-kidney transplants: a retrospective analysis; Douzdjian V et al.; Intraperitoneal placement of the pancreas allograft, usually through a midline incision, has so far achieved the best results in pancreas transplantation . The usefulness and safety of a transverse incision has not been previously reported . The purpose of this study was to compare midline and transverse incisions, with respect to wound complications and outcome, in simultaneous pancreas-kidney transplant recipients with intraperitoneal placement of the pancreatic graft . The incidence of deep abscess formation, superficial abscess formation, wound leak, and fascial dehiscence, as well as graft survival, were retrospectively compared in 41 bladder-drained simultaneous pancreas-kidney recipients with a midline incision and in 15 with a transverse incision . The overall incidence of wound complications was similar (34% vs 20%, P = NS) in the two groups . Deep abscess formation occurred more frequently in the midline group (27% vs 0%, P = 0.02) . Staphylococcus epidermidis and Candida albicans were the most common microbial isolates from deep abscesses . Multivariate logistic regression analysis revealed donor age 40 years or older (P = 0.04), the occurrence of a bladder leak (P = 0.05), and a peak serum amylase in the 1st week of 1000 IU/l or greater (P = 0.02) to be independent risk factors for the development of wound complications . The type of incision, however, was not found to be an independent risk factor . Patient (90% vs 83%, P = NS), pancreas allograft (78% vs 82%, P = NS), and kidney allograft (83% vs 70%, P = NS) survival rates were similar for the midline and transverse groups . We conclude that the transverse incision is a reasonable alternative to the midline incision in simultaneous pancreas-kidney transplantation and it is presently the incision of choice at our institution . It offers excellent exposure and is associated with a similar wound complication rate and outcome when compared to the midline incision. J Clin Microbiol, 1996 Jan, 34(1), 25 - 8 PCR monitoring of response to liposomal amphotericin B treatment of systemic candidiasis in neutropenic mice; van Deventer AJ et al.; When a diagnosis of invasive candidiasis has been made, treatment with toxic fungicidal agents is inevitable . The crucial decision of when to stop such treatment is difficult to make, because cultures are often negative despite ongoing invasive candidiasis and can therefore not be used as a reliable parameter of effective therapy . In the present study, the use of PCR in monitoring the therapeutic efficacy of antifungal treatment with liposomal amphotericin B was evaluated by using neutropenic mice with systemic candidiasis . Blood cultures of infected mice treated with different doses of liposomal amphotericin B were only positive at the early onset of the infection process and became sterile within 3 days; this was true even with mice treated with 1 mg of liposomal amphotericin B per kg of body weight that experienced a relapse of infection 14 days later . A significant correlation between presence of Candida albicans in the kidneys and PCR results obtained with blood was demonstrated . Thus, PCR results obtained with blood samples correlated well with the therapeutic efficacy of antifungal treatment. J Laryngol Otol, 1996 Jan, 110(1), 13 - 8 Acute labyrinthitis associated with systemic Candida albicans infection in ageing mice; Ashman RB et al.; The yeast Candida albicans is an important opportunistic pathogen that has been associated with disease of the inner ear . This study describes the histopathology of acute labyrinthitis caused by systemic infection with C . albicans in aging inbred mice . Within four days after infection, yeast and hyphal forms of C.albicans were found in the membranous labyrinth . The utricle and the adjacent parts of the ampullary regions of the semicircular canals were most severely affected, but damage was also seen in the scala media, the scala tympani, the saccule, and the scala vestibuli . In the utricle, the lining epithelium of the membranous labyrinth was disrupted, and the lining cells of the vestibular membrane showed foci in which the membrane was disrupted . The data suggest that age may represent a risk factor for fungal labyrinthitis. Ter Arkh, 1996, 68(3), 80 - 3 {Pulmonary aspergillosis in patients with disseminated processes in the lungs}; Vlasenko SIu et al.; Sera of 30 patients with disseminated processes in the lungs of various etiology were examined for the presence of specific IgG to antigens of Aspergillus fumigatus (A.f.) and Candida albicans (C.a.) using solid phase enzyme immunoassay . Elevated concentrations of IgG to A . f . and C . a . were found in 6 and 12 patients, respectively . Serodiagnosis was confirmed by a direct detection of the fungi in the bronchi (cytology of the lavage, culturing) . It is highly probable that opportunistic fungi may be involved in pulmonary dissemination . Therefore, patients with disseminated pulmonary diseases should be examined for opportunistic fungi. Cytokine, 1996 Jan, 8(1), 42 - 8 Ex vivo effects of macrophage colony-stimulating factor on human monocyte activity against fungal and bacterial pathogens; Roilides E et al.; The ex vivo effects of macrophage colony-stimulating factor (M-CSF) on antifungal and antibacterial activities of human elutriated monocytes were studied . Cells were isolated prior to the initiation of therapy, on day 3 and at week 7, in six patients with an advanced malignancy receiving M-CSF in a phase I study . Superoxide anion production by monoctyes in response to N-formyl methionyl leucyl phenylalanine was enhanced at day 3 of therapy (P = 0.011) . In addition, at day 3, fungicidal activity against blastoconidia of Candida albicans was enhanced by M-CSF treatment (P = 0.026), whereas antifungal activity against hyphae of Aspergillus fumigatus was not significantly changed . Bactericidal activity against Staphylococcus aureus was increased at day 3 (P = 0.004) . By Northern blot analysis, M-CSF does not upregulate the expression of components of the NADPH-oxidase, the multicomponent enzyme system responsible for generation of superoxide radicals by monocytes . Instead, the predominant effect of M-CSF on circulating monocytes is probably a post-transcriptional effect . In conclusion, these findings suggest that administration of M-CSF to patients may enhance microbicidal activities and thus may provide a useful adjunct to conventional antimicrobial therapy. J Pharm Pharmacol, 1996 Jan, 48(1), 64 - 7 Susceptibility of mice to bacterial and fungal infections after intragastric administration of ebselen; Nozawa R et al.; The seleno-organic compound ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) has anti-inflammatory activity and exhibits glutathione peroxidase-like activity in-vitro . Ebselen inhibited candidacidal activity over the same range of concentrations as it inhibited the production of microbicidal H2O2 by human neutrophils and macrophage-like cells . Therefore, the long-term administration of ebselen might be expected to induce an immunocompromised state in the host . To examine such a possibility, mice (5-weeks-old ddY, male) were given daily intragastric doses of 0, 10 or 100 mg/kg-1 ebselen for 21 days and then infected intraperitoneally with Candida albicans (10(8) cells/mouse), Pseudomonas aeruginosa (1.5 x 10(7) cells/mouse) or methicillin-resistant Staphylococcus aureus (5 x 10(8) cells/mouse) . Ebselen at none of the tested doses affected the increase in body weight of mice during administration of the drug . No evidence was obtained that mice became more susceptible to the various microorganisms after the administration of ebselen at any tested dose. J Pharm Pharmacol, 1996 Jan, 48(1), 60 - 3 Antimicrobial activity of electrochemical silver ions in nonionic surfactant solutions and in model dispersions; Scalzo M et al.; The microbicidal effectiveness against Gram-positive and Gram-negative bacteria and Candida albicans of electrochemical silver ions in aqueous solutions containing nonionic surfactants was investigated . From the perspective of the possible use of anodic silver as a preservative in cosmetic or pharmaceutical preparations, microbicidal efficacy was also studied in oil/water model dispersions . Surfactants and botanical extracts partially inhibited the microbicidal effectiveness of anodic silver . Nevertheless in all the experimental conditions, silver ions reduced the microbial concentration up to 4 log units of the starting inoculum in less than 6 h . The wide microbicidal spectrum and the high rate of kill of silver ions appear, therefore, attractive enough to suggest a possible utilization of anodic silver as a preserving agent. Farmaco, 1996 Jan, 51(1), 71 - 4 Synthesis and antimicrobial activity of some 2,5-disubstituted 1,3,4,-thiadiazole derivatives; Mamolo MG et al.; A series of 5-substituted 2-arylamino-1,3,4-thiadiazole derivatives was prepared . The antimicrobial activity of these compounds against some strains of bacteria and a strain of Candida albicans was determined, together with that of the corresponding thiosemicarbazone derivatives, which are intermediates in the synthetical procedure. Bioorg Med Chem, 1996 Jan, 4(1), 97 - 103 Design, synthesis and in vitro evaluation of pyridinium ion based cyclase inhibitors and antifungal agents; Rose IC et al.; The design, synthesis and in vitro biological evaluation of pyridinium ion based inhibitors of oxidosqualene cyclase enzymes are reported . N-Alkyl- and N-prenylpyridinium ions have been found to be potent and specific inhibitors of Candida albicans oxidosqualene-lanosterol cyclase and to exhibit antifungal activity . The ability of pyridinium ions to inhibit the C . albicans cyclase increases with increasing structural resemblance to a putative monocyclized species formed during the course of the cyclization process . The N-(4E,8E)-5,9,13-trimethyl-4,8,12-tetradecatrien-1- ylpyridinium cation 1 inhibits the C . albicans enzyme at concentrations more than 100-fold lower than does the directly analogous piperidinium derivative 4. Ophthalmology, 1996 Jan, 103(1), 37 - 40 Corneal anesthetic abuse and Candida keratitis; Chern KC et al.; PURPOSE: Topical corneal anesthetic abuse is a self-inflicted injury, causing profound corneal morbidity . Superimposed infection is an important complicating factor . The authors report four patients with confirmed topical anesthetic abuse of the cornea, in whom Candida keratitis developed . METHODS: A retrospective review of the medical records of four patients with confirmed topical corneal anesthetic abuse and fungal keratitis . RESULTS: A 21-year-old woman, two 28-year-old women, and a 35-year-old man were included in the study . All these patients sustained a corneal injury, prompting the chronic use of topical anesthetics (0.5% proparacaine hydrochloride in 3 patients, and 0.5% tetracaine hydrochloride and 0.4% benoxinate hydrochloride in the other) . Corneal findings included epithelial defects in all patients, focal infiltrate in one patient, and ring-shaped stromal infiltrate in three patients . Topical anesthetic was discontinued, all patients initially were treated empirically with antibacterial agents, and three patients received topical corticosteroids . Subsequent corneal cultures grew Candida spp, Candida albicans specifically in three patients, and local and systemic antifungal therapy was started . Corneas in two patients re-epithelialized; a conjunctival flap was performed on another patient with a descemetocele; and the remaining patient was lost to follow-up, although repeat fungal cultures yielded no growth . CONCLUSIONS: Corneal superinfection with Candida may occur during topical anesthetic abuse . Therapy includes discontinuation of the anesthetic and institution of antifungal therapy. J Neuroimmunol, 1996 Jan, 64(1), 9 - 17 Biomolecular events involved in the establishment of brain anticandidal resistance; Mazzolla R et al.; Using a murine model, we have demonstrated the establishment of cerebral resistance to local lethal challenge with Candida albicans strain CA-6, by previous intracerebral (i.c.) infection with the low-virulent strain PCA-2 . Here we show that i.c . infection with PCA-2 is effective in drastically reducing brain colonization following secondary infection with CA-6 . As assessed by colony forming unit assay and histopathological analysis, microbial counts are impaired, granuloma formation and hyphal growth are also reduced in brains of PCA-2- and CA-6-infected mice with respect to CA-6-challenged mice . Furthermore, using PCR studies, we found that, while PCA-2 (i.e . healing infection) induces transient cytokine gene expression in the mouse brain, CA-6 lethal challenge results in long-lasting (until mouse death) high levels of all cytokine gene transcripts assessed . Finally brains from mice that will resist CA-6 challenge, because of previous infection with PCA-2, also exhibit a transient induction of all cytokine genes . Only IL-1 beta remains highly expressed at all time- points tested . Overall, these results provide evidence that healing and non-healing C . albicans i.c . infections differ in the immune reaction(s) locally evoked, at least in terms of cytokine gene expression, strongly suggesting cytokine involvement in the establishment of brain anticandidal resistance. Can J Microbiol, 1996 Jan, 42(1), 76 - 9 Changes in glutathione metabolic enzymes during yeast-to-mycelium conversion of Candida albicans; Manavathu M et al.; Candida albicans is a dimorphic yeast capable of producing alternate morphological forms (yeast or mycelium) in response to environmental changes . The intracellular level of glutathione, which helps to maintain the redox potential of the cell, is decreased significantly during the thermal induction of yeast-to-mycelium conversion . The reason for the decline of glutathione in the mycelial form is not understood . We have, therefore, investigated the levels of glutathione reductase, glutathione S-transferase, gamma-glutamyltranspeptidase, and glutathione peroxidase, four key enzymes involved in glutathione metabolism, in the yeast and mycelial forms . Yeast cells of C . albicans 3153A were induced in Lee's medium (pH 6.5) at 37 degrees C for 3 h to produce germ tubes . Cell lysates were prepared from yeast and mycelial cells, and glutathione reductase, glutathione S-transferase, gamma-glutamyltranspeptidase, and glutathione peroxidase were assayed spectrophotometrically . There was a 640% increase of the level of gamma-glutamyltranspeptidase in the germ tubes as compared with the yeast cells . No other significant alteration of the levels of enzymes was noted . This increased activity of gamma-glutamyltranspeptidase, which cleaves the glutamic acid residue of glutathione (Glu-Cys-Gly) appears to be, at least in part, responsible for the rapid decrease of the intracellular glutathione in C . albicans during the yeast-to-mycelium conversion. Phytochemistry, 1996 Jan, 41(1), 111 - 6 Secoiridoids and antifungal aromatic acids from Gentiana algida; Tan RX et al.; Fractionation of an aqueous acetone extract of the whole herb of Gentiana algida gave one new {2'-(o,m-dihydroxybenzyl)sweroside} and five known secoiridoids, together with anofinic acid, fomannoxin acid, sitosterol, daucosterol, stigmasterol, oleanolic acid, orientin and gentianose . The structures were determined by spectral methods and a few chemical transformations . Anofinic acid and fomannoxin acid were found to be active against Cladosporium cucumerinum, a plant pathogenic fungus . Preliminary structure-activity studies indicated that the presence of carboxylic moieties in these acids was presumably a precondition for activity, whereas their methyl esters, inactive to the fungus, were active against the human pathogenic yeast Candida albicans . The chemotaxonomic significance of the isolates is discussed briefly. J Bacteriol, 1996 Jan, 178(1), 121 - 9 The sea pansy Renilla reniformis luciferase serves as a sensitive bioluminescent reporter for differential gene expression in Candida albicans; Srikantha T et al.; The infectious yeast Candida albicans progresses through two developmental programs which involve differential gene expression, the bud-hypha transition and high-frequency phenotypic switching . To understand how differentially expressed genes are regulated in this organism, the promoters of phase-specific genes must be functionally characterized, and a bioluminescent reporter system would facilitate such characterization . However, C . albicans has adopted a nontraditional codon strategy that involves a tRNA with a CAG anticodon to decode the codon CUG as serine rather than leucine . Since the luciferase gene of the sea pansy Renilla reinformis contains no CUGs, we have used it to develop a highly sensitive bioluminescent reporter system for C . albicans . When fused to the galactose-inducible promoter of GAL1, luciferase activity is inducible; when fused to the constitutive EF1 alpha 2 promoter, luciferase activity is constitutive; and when fused to the promoter of the white-phase-specific gene WH11 or the opaque-phase-specific gene OP4, luciferase activity is phase specific . The Renilla luciferase system can, therefore, be used as a bioluminescent reporter to analyze the strength and developmental regulation of C . albicans promoters. Gene, 1995 Dec 29, 167(1-2), 173 - 7 Isolation and characterization of two chitinase-encoding genes (cts1, cts2) from the fungus Coccidioides immitis; Pishko EJ et al.; Two chitinase (CTS)-encoding genes (cts) from Coccidioides immitis (Ci), a respiratory fungal pathogen of humans, were cloned and sequenced . Both the genomic and cDNA sequences are presented . The transcription start points and poly(A)-addition sites were confirmed . The cts1 gene contains five introns and a 1281-bp ORF which translates a 427-amino-acid (aa) protein of 47.4 kDa . The cts2 gene contains two introns and a 2580-bp ORF which translates a 860-aa protein of 91.4 kDa . The deduced CTS1 protein showed highest homology to the Aphanocladium album and Trichoderma harzianum CTS (74% and 76%, respectively), while CTS2 showed highest homology to the CTS of Saccharomyces cerevisiae (Sc) and Candida albicans (47% and 51%, respectively) . The putative N-terminal sequence of the mature CTS1 protein also showed 89% homology to the reported N-terminal sequence of a 48-kDa complement fixation antigen (CF-Ag) of Ci which has demonstrated chitinase activity . The CF-Ag is a clinically important antigen used in serodiagnosis of this fungal