Br J Dermatol, 1992 Feb, 126 Suppl 39, 2 - 7 Terbinafine: mode of action and properties of the squalene epoxidase inhibition; Ryder NS; Terbinafine (Lamisil) has primarily fungicidal action against many fungi as a result of its specific mechanism of squalene epoxidase inhibition . Treated fungi accumulate squalene while becoming deficient in ergosterol, an essential component of fungal cell membranes . The cidal action is closely associated with the development of high intracellular squalene concentrations, which are believed to interfere with fungal membrane function and cell wall synthesis . In the case of Candida albicans, growth inhibition with terbinafine appears to result from the ergosterol deficiency . The filamentous form of this fungus is more susceptible than the yeast form . Measurement of ergosterol biosynthesis by incorporation of radiolabelled precursors indicates a correlation between inhibition of growth and ergosterol biosynthesis in a range of pathogenic fungi . Terbinafine is a potent non-competitive inhibitor of squalene epoxidase from Candida (Ki = 30 nM) . In contrast, inhibition of rat liver squalene epoxidase only occurs at higher drug concentrations (Ki = 77 microM), and is competitive with squalene . Thus, terbinafine has no effect on cholesterol biosynthesis in vivo . Squalene epoxidase is not an enzyme of the cytochrome P-450 type, thereby avoiding potential inhibition of this class of enzymes. J Clin Microbiol, 1992 Feb, 30(2), 411 - 7 Presence of human antibodies reacting with Candida albicans O-linked oligomannosides revealed by using an enzyme-linked immunosorbent assay and neoglycolipids; Hayette MP et al.; In order to study the presence of antibodies directed against Candida albicans O-linked oligomannosides (oligomannosides O) in patient sera, we have developed an enzyme-linked immunosorbent assay (ELISA) involving neoglycolipids constructed with these residues (NGLO) . Oligomannosides O released by mild alkaline degradation of the C . albicans cell wall phosphopeptidomannan (PPM) contained one to seven mannose residues, among which the quantitatively major components, mannobiose and mannotriose, were shown by 1H nuclear magnetic resonance to contain exclusively alpha (1-2) linkages . The pool of oligomannosides was converted to neoglycolipids by coupling them to 4-hexadecylaniline in an equimolar reaction checked by thin-layer chromatography . We have tested against these neoantigens, coated on ELISA plates, 15 pairs of sera corresponding to individual seroconversions observed in 15 patients during the course of a mycological and serological survey of candidiasis . For all patients, seroconversions resulted in an increased level of antibodies against NGLO . A significant correlation was observed between the results of ELISA-NGLO, ELISA involving the original PPM molecule, and routine antibody detection tests, indirect immunofluorescence assay, and cocounterimmunoelectrophoresis . These results therefore demonstrate the synthesis of human antibodies reactive with oligomannosides O constitutive of the C . albicans mannan molecule which have been previously described as exhibiting an inhibitory effect on human lymphocytic proliferation. Oral Microbiol Immunol, 1992 Feb, 7(1), 51 - 2 Antifungal activities of salivary histidine-rich polypeptides against Candida albicans and other oral yeast isolates; Rayhan R et al.; Twenty-six oral yeast isolates from 26 donors were tested for their susceptibility to salivary histidine-rich polypeptide-4 (HRP-4) in blastospore viability assays . HRP-4 was observed to inhibit blastospore division in all of the yeast isolates, although inhibition was variable depending upon both species and strain tested . Nine species of Candida and 2 strains of Trichosporon pullulans were included in the study . No significant differences in susceptibility to HRP-4 could be seen, irrespective of where in the oral cavity the yeast isolate was obtained. Oral Microbiol Immunol, 1992 Feb, 7(1), 38 - 43 Salivary anti-candidal assays; Santarpia RP 3rd et al.; Inhibition of Candida albicans blastospore viability by parotid, submandibular-sublingual and whole salivas could not be determined by direct assay of yeast cells in each respective saliva . Determination of antifungal activity could, however, be carried out if saliva was first preincubated with Candida cells and this was immediately followed by removal of saliva and resuspension of yeast cells in nonenriched buffers of pH 5-7 for appropriate incubation periods . To attain accurate reproducible quantitative data, parotid, submandibular-sublingual and whole salivas each required different preincubation times with C . albicans as well as prior acidification and boiling . Acidification was also necessary for optimizing the germ tube assay although, in contrast to blastospore viability, inhibition of blastospore-germ tube conversion could be determined directly in saliva . Salivary antifungal effects on blastospore division were negligible at yeast cell concentrations greater than 10(6) colony-forming units per ml and were found to be independent of pH, whereas salivary inhibition of germ tube formation was significant only at pH 5 in the assay systems employed . The requirement for acidification and an observed enhancement of antifungal activity on aqueous dilution of the saliva suggested that only a fraction of the salivary antifungal components present in saliva were available in the free form to exert their biological activity . These results open up the possibility of investigating salivary antifungal activity in human health and disease. Oral Microbiol Immunol, 1992 Feb, 7(1), 32 - 7 Mechanisms of aggregation accompanying morphogenesis in Candida albicans; Holmes AR et al.; Cultures of Candida albicans yeast cells do not normally aggregate, but extensive aggregation accompanies the induction of mycelial growth, indicating the occurrence of cell surface changes during the yeast to mycelial transition . Aggregation correlated with the formation of germ tubes as did changes in surface charge determined by attachment to ion exchange sepharose beads . Yeast cells of all strains examined were negatively charged and attachment to positively charged (DEAE) sepharose beads increased following germ tube formation . If Mg2+ was present during germ tube formation, a high degree of clumping occurred that could only be dispersed by treatment with protein-disrupting agents . Trypsin, chymotrypsin, SDS, urea, guanidine HCl and dithiothreitol but not EDTA or EGTA caused irreversible dispersal of aggregates, although germ tube aggregates dispersed by treatment with buffers at high pH reaggregated if neutralized or if calcium ions were added . Germ tube cultures produced in divalent cation-deprived medium formed aggregates that were readily dispersed by washing . However, the addition of Mg2+ or other divalent cations (Ca2+, Zn2+, Cu2+, Fe2+) caused immediate aggregation of these cultures . These results suggest that divalent cation crossbridging between opposing anionic sites and protein interactions act synergistically to promote aggregation of C . albicans germ tube cells. Can J Microbiol, 1992 Feb, 38(2), 135 - 42 Effects of culture conditions on the in vitro infection of fibroblasts by Candida albicans; Merkel GJ; The effects of yeast culture age, carbon source, growth temperature, and germ-tube inducers on adherence to primary fibroblast cultures was studied in conjunction with the determination of adherence-mediated mammalian cell damage by measuring chromium-51 release from fibroblast monolayers . The results indicated that yeast culture age affected adherence only when the yeasts were grown at 37 degrees C, not after growth at 28 degrees C . At 37 degrees C, quantitatively fewer exponential-phase, glucose- or galactose-grown yeasts adhered to fibroblasts than did yeasts that were in lag or stationary phases . The reduced adherence correlated with less chromium-51 release and reduced germ-tube formation . The addition of germ-tube inducers, such as N-acetyl-D-glucosamine or serum, to exponential-phase yeasts caused an increase in germ-tube formation with a concomitant increase in yeast adherence and release of chromium-51 from the monolayers . Exponential-phase galactose-grown yeasts were more responsive to serum-induced germ-tube formation, germ-tube elongation, and fibroblast adherence than were exponential-phase glucose-grown yeasts . In addition, exponential-phase galactose-grown yeasts caused more chromium-51 release from monolayers in the presence of serum than did glucose-grown yeasts . Overall, conditions that enhanced germ-tube formation and elongation resulted in greatest adherence-mediated damage to the monolayers. J Antimicrob Chemother, 1992 Feb, 29(2), 129 - 36 The postantifungal effect of 5-fluorocytosine on Candida albicans; Scalarone GM et al.; The in-vitro postantifungal effect (PAFE) of 5-fluorocytosine for Candida albicans for short periods of time was investigated . Yeast cells were exposed for 0.5, 1 or 2 h to a range of concentrations (0.1-3.2 mg/L) of 5-fluorocytosine . The PAFE was quantitated by determinations of the number of colony forming units at hourly intervals (0-10 h) after removal of the drug by dilution . The length of the PAFE was dependent upon the concentration of 5-fluorocytosine and the duration of exposure . An exposure time of 0.5 h resulted in PAFE's ranging from 0 to 4.2 h . Exposure times of 1 and 2 h resulted in longer PAFEs and in many instances suppression of cell growth was seen for the entire evaluation period (up to ten hours). J Chemother, 1992 Feb, 4(1), 35 - 40 Generation of superoxide anion and candidacidal activity by lipopolysaccharide-treated macrophages from patients affected by neoplasia; Merendino RA et al.; Macrophages, derived from in vitro cultured monocytes from both healthy donors and patients affected by metastatic breast cancer, treated or not with Escherichia coli lipopolysaccharide (LPS), were tested for phagocytosis and intracellular killing of Candida albicans and superoxide anion release . We found a marked impairment in intracellular killing closely linked to the lack of superoxide production in macrophages from patients affected by neoplasia treated or not with LPS . On the other hand, the LPS treatment significantly enhanced the phagocytic activity of all the macrophage populations tested, except for phagocytes obtained from patients affected by neoplasia and differentiated in autologous serum. J Antimicrob Chemother, 1992 Feb, 29(2), 195 - 205 Efficacy and safety of itraconazole in the long-term treatment of onychomycosis; Piepponen T et al.; Sixty-one patients with a clinical diagnosis of onychomycosis in finger or toe nails were treated with itraconazole 100 mg/day or griseofulvin 500 mg/day for six to nine months . The infective causes were Trichophyton rubrum, Trichophyton mentagrophytes, or Trichophyton violaceum, and in two cases Candida albicans . A total of 27 finger and 390 toe nails were infected . Statistically significant intragroup reductions from baseline symptom severity values were seen at endpoint (month 6 or 9) for both treatment groups for all parameters: colour change, thickness, brittleness and unaffected area . No clinically or statistically significant differences between the treatment groups were seen at endpoint . However, the itraconazole group continued to improve during the follow-up, while the mean symptom severity ratings remained the same in the griseofulvin group . All itraconazole patients and 85% of griseofulvin patients were rated as cured or markedly improved at endpoint . Nineteen out of 26 evaluable itraconazole patients (73%) remained cured during the three month follow-up period, compared with 12 out of 17 griseofulvin patients (71%) . The rather large number of drop-outs, especially among griseofulvin patients, makes it difficult to draw definitive conclusions of the symptom recurrence . Two itraconazole patients stopped medication due to an adverse event, compared to four patients in the griseofulvin group . The clinical laboratory data on itraconazole-treated patients did not show any statistically or clinically significant changes . In conclusion, itraconazole was at least as effective as griseofulvin in the treatment of onychomycosis . The itraconazole group continued to improve after the treatment was stopped . The results show that itraconazole 100 mg/day is safe and efficient in the long-term treatment of fungal nail infections. Arch Surg, 1992 Feb, 127(2), 146 - 51 Interleukin 1 and its relationship to endotoxin tolerance; Leon P et al.; Endotoxin (lipopolysaccharide {LPS})-induced cytokine release has been implicated in the pathogenesis of sepsis . Sublethal doses of LPS induce tolerance to a septic insult . This study evaluated pretreatment with interleukin 1 (IL-1) against an LPS challenge and examined its relationship to endotoxin tolerance . C3H/HeN mice (N = 100) were injected intraperitoneally with phosphate-buffered saline (control group), IL-1 (200 micrograms/kg), or LPS (1 mg/kg) for 3 days . On day 5, peritoneal macrophages were harvested and assayed for antimicrobial activity (superoxide anion production and Candida albicans phagocytosis) . Serum cytokine levels and survival after an LPS challenge on day 5 were also assessed . Pretreatment with IL-1 or LPS significantly increased superoxide anion production, C albicans phagocytosis, and survival compared with pretreatment with phosphate-buffered solution . Interleukin 6 levels significantly decreased in the IL-1 and LPS groups . Peak levels of tumor necrosis factor significantly decreased only in the LPS group . Thus, pretreatment with IL-1 or low doses of LPS may exert protective effects by decreasing levels of interleukin 6 while increasing antimicrobial activity . Mice pretreated with IL-1 were protected from endotoxin despite elevated peak levels of tumor necrosis factor, suggesting a different mechanism for endotoxin tolerance than for tolerance to tumor necrosis factor. Clin Exp Immunol, 1992 Feb, 87(2), 316 - 21 Interaction and intracellular killing of Candida albicans blastospores by human polymorphonuclear leucocytes, monocytes and monocyte-derived macrophages in aerobic and anaerobic conditions; Thompson HL et al.; Polymorphonuclear leucocytes (PMN), monocytes and monocyte-derived macrophages were capable of interacting with opsonized C . albicans in both aerobic and anaerobic conditions . Superoxide anion release by these cells was inhibited in anaerobic conditions while lysozyme release and phagocytosis were equally efficient in both aerobic and anaerobic conditions . All cell types tested were capable of intracellular killing of C . albicans and this appeared to be maximum at 6 h for monocytes and macrophages and 24 h for PMN . Monocytes killed the lowest number of organisms, 1 x 10(6), and the killing was similar for aerobic and anaerobic conditions . In contrast, PMN and macrophages demonstrated greater killing of C . albicans in aerobic conditions compared with anaerobic conditions; PMN killed 1.9 x 10(6) organisms and macrophages 3 x 10(6) when incubated anaerobically . Inhibitors of oxygen metabolism decreased intracellular killing of C . albicans by macrophages and PMN in aerobic but not anaerobic conditions . The oxygen reaction products involved in the killing of C . albicans appeared to be different however: macrophage killing was decreased by superoxide anion and hydrogen peroxide inhibitors . PMN killing was decreased by superoxide anion, hydrogen peroxide, hypochlorous acid and hydroxyl radical inhibitors . The present study shows that although monocytes, macrophages and PMN function similarly in their interaction with C . albicans, they appear to use different oxygen reactive products for the intracellular killing of C . albicans. Zh Mikrobiol Epidemiol Immunobiol, 1992 Feb, (2), 68 - 70 {Antibody avidity in candidiasis patients}; Karaev ZO et al.; The properties of antibodies to Candida albicans in healthy persons, candidiasis patients and patients with somatic pathology of nonmycotic genesis were studied . Healthy persons were found to have the highest avidity of antibodies at the minimal neutralizing dose of the antigen . In all groups the titers of antibodies were inversely related to their avidity. Biochim Biophys Acta, 1992 Jan 23, 1115(3), 225 - 9 N3-haloacetyl derivatives of L-2,3-diaminopropanoic acid: novel inactivators of glucosamine-6-phosphate synthase; Milewski S et al.; N3-Haloacetyl derivatives of L-2,3-diaminopropanoic acid, novel glutamine analogs, were shown to be strong inhibitors of glucosamine-6-phosphate synthase from bacteria and Candida albicans . The inhibition was competitive with respect to glutamine and non-competitive with respect to D-fructose-6-phosphate . In the absence of glutamine, the tested compounds inactivated glucosamine-6-phosphate synthase from C . albicans with Kinact = 0.5 microM, 0.55 microM and 18.5 microM for bromoacetyl-, iodoacetyl- and chloroacetyl derivatives of L-2,3-diaminopropanoic acid, respectively . The inactivation obeyed the criteria for active site-directed modification. Proc Natl Acad Sci U S A, 1992 Jan 15, 89(2), 519 - 23 Classification of fungal chitin synthases; Bowen AR et al.; Comparison of the chitin synthase genes of Saccharomyces cerevisiae CHS1 and CHS2 with the Candida albicans CHS1 gene (UDP-N-acetyl-D-glucosamine:chitin 4-beta-N-acetylglucosaminyltransferase, EC 2.4.1.16) revealed two small regions of complete amino acid sequence conservation that were used to design PCR primers . Fragments homologous to chitin synthase (approximately 600 base pairs) were amplified from the genomic DNA of 14 fungal species . These fragments were sequenced, and their deduced amino acid sequences were aligned . With the exception of S . cerevisiae CHS1, the sequences fell into three distinct classes, which could represent separate functional groups . Within each class phylogenetic analysis was performed . Although not the major purpose of the investigation, this analysis tends to confirm some relationships consistent with current taxonomic groupings. FEMS Microbiol Lett, 1992 Jan 15, 69(3), 223 - 8 Fungicidal effect of human lactoferrin against Candida albicans; Soukka T et al.; Human lactoferrin (LF) in its iron-free state (apo LF), killed Candida albicans in a time- and dose-dependent way . The lethal effect was stronger at pH 7.0 than at pH 5.5 and maximum inhibition at neutral pH was achieved in 25 min when the fungal cells were exposed to LF in 0.05 mM KCl at 37 degrees C . Fe(3+)-saturated LF had no fungicidal activity . Apo LF-mediated killing was also temperature-dependent with enhanced inhibition at higher temperatures (37 degrees, 42 degrees C) . The presence of 1 mM D-glucose did not affect the candidacidal activity of apo LF but both phosphate and bicarbonate ions at physiological salivary concentrations completely blocked the anti-fungal effect . Therefore it seems unlikely that LF belongs to the major host defence factors against oral candidosis. Antimicrob Agents Chemother, 1992 Jan, 36(1), 64 - 7 Comparison of SCH 39304, fluconazole, and ketoconazole for treatment of systemic infections in mice; Cacciapuoti A et al.; SCH 39304 was compared with fluconazole and ketoconazole in a systemic Candida albicans infection in mice (10(6) CFU per mouse) . Results were based on survival rates and CFU in kidneys following once-daily oral treatment of 2, 5, or 10 days duration . In normal mice, SCH 39304 (dose to reduce kidney counts by 4 log units, 0.5 mg/kg of body weight) was 3 and 200 times more active than fluconazole and ketoconazole, respectively . In immunocompromised mice (gamma irradiation, 600 rads), SCH 39304 (dose to reduce kidney counts by 4 log units, 1.3 mg/kg) was 35 and greater than 100 times more active than fluconazole and ketoconazole, respectively . In normal mice, when the infecting inoculum varied from 10(5) to 10(7) CFU, only a fivefold increase in the dose to reduce kidney counts by 4 log units was observed with SCH 39304 . Excellent protection was also seen when mice were treated with a single oral dose of SCH 39304 up to 24 h prior to infection with C . albicans . Studies in a systemic C . albicans infection model indicated that SCH 39304 is equally efficacious following either oral or intravenous administration . In a systemic Aspergillus flavus infection, mice treated with SCH 39304 (5 mg/kg) survived twice as long (16 days) as those treated with fluconazole (50 mg/kg) or controls did. Acta Derm Venereol, 1992, 72(2), 109 - 11 Impairment of some granulocyte functions in Sweet's syndrome; von den Driesch P et al.; Chemotaxis, phagocytic and intracellular killing activities of polymorphonuclear leukocytes (PMNL) were investigated in vitro in 7 patients suffering from the acute phase of Sweet's syndrome . A moderate but consistent impairment of neutrophilic chemotactic activity (NCA) was revealed in all patients . Intracellular killing of blastospores of Candida albicans was diminished in 5/7 patients . Phagocytosis and oxidase activities were within normal levels . These results point to an alteration of some PMNL functions in the acute phase of Sweet's syndrome. Gene, 1992 Jan 2, 110(1), 123 - 8 Cloning and characterization of the gene encoding the ADP-ribosylation factor in Candida albicans; Denich KT et al.; We have cloned and sequenced the gene (ARF) encoding the ADP-ribosylation factor (ARF) of Candida albicans . The gene contains an open reading frame of 537 nucleotides (nt) that codes for a protein with an Mr of 20,259 . The C . albicans ARF gene is 67-70% identical at the nt level to other ARF sequences including those of humans; the deduced amino acid sequence of C . albicans ARF shows a 78-83% identity and 89-92% similarity to the other ARFs . Southern analysis of C . albicans genomic DNA suggested the presence of a second ARF gene . The presence of multiple ARF genes is a consistent finding among the other organisms previously shown to have ARFs. J Clin Microbiol, 1992 Jan, 30(1), 149 - 53 Serotype prevalence of Candida albicans from blood culture isolates; Brawner DL et al.; Blood culture isolates of Candida albicans were collected from 102 patients in Seattle, Wash., hospitals (n = 77) and Hong Kong (n = 25) . The patients were classified by immune status into two groups . Group I patients were severely immunosppression, and group II patients had underlying risk factors for candidemia but no underlying immunosuppression . Serotyping by Hasenclever tube agglutination was done . In the Seattle area, the odds of fungemia with type B C . albicans were 3.62 times greater than the odds of type B fungemia in group II patients . Although the odds ratio could not be computed for Hong Kong patients, the direction of the relationship in this population was consistent with the data on Seattle patients . Despite the magnitude of the odds ratios, the relative prevalence of type B over type A in group I compared with group II was not significant when analyzed separately by region, probably because of relatively low numbers of isolates in group II . Accepting that the effect of immune status on serotype is equivalent across regions but presupposing that a regional effect on type B prevalence exists, the pooled odds for fungemia with serotype B in group I patients are increased 5.4-fold over those of group II patients . Logistic regression analysis controlling for region gave similar results. Diagn Microbiol Infect Dis, 1992 Jan, 15(1), 5 - 11 The impact of converting to a biphasic blood-culture system on the overall cost and the incidence of pseudobacteremia; Heelan JS et al.; After converting from a conventional broth (CB) system to a biphasic (BP) agar-slide blood-culture system (Septi-Chek), our laboratory noted an increase in positive blood cultures in general, and in coagulase-negative staphylococci (CNS) in particular . To investigate these findings, we compared all blood cultures collected over a 21-month period using CB and then BP systems, totaling 28,199 blood cultures . The frequency of positive blood cultures increased from 9.2% to 12.7% (p less than 0.0001), whereas CNS isolation increased from 2.6% to 5.2% (p less than 0.0001) . There was no significant change in the incidence of true primary or secondary bacteremia due to CNS (p = 0.9) . The isolation of other pathogens, including Staphylococcus aureus, Candida albicans, Bacteroides species, and Gram-negative bacilli increased from 6.5% to 7.1% (p less than 0.05) . We estimated the cost of processing 28,000 blood cultures by both CB and BP systems, using positivity rates of 9.2% and 12.7%, respectively, and standards provided by the College of American Pathologists (CAP, 1991) for workload hours of technologist time . We calculated a higher overall cost for the BP system . However, the use of this system eliminated the use of needles and syringes for subculture of bottles showing no growth, thus decreasing the risk of technologist exposure to body fluids . Despite the increased cost and more frequent occurrence of pseudobacteremia, the enhanced sensitivity and increased safety of the BP system justified its use in the prompt identification of patients with true bacteremia. J Bacteriol, 1992 Jan, 174(1), 222 - 32 A zinc finger protein from Candida albicans is involved in sucrose utilization; Kelly R et al.; A sucrose-inducible alpha-glucosidase activity that hydrolyzes sucrose in Candida albicans has been demonstrated previously . The enzyme is assayable in whole cells and was inhibited by both sucrose and maltose . A C . albicans gene (CASUC1) that affects sucrose utilization and alpha-glucosidase activity was cloned by expression in a Saccharomyces cerevisiae suc2 mutant (2102) devoid of invertase genes . CASUC1 enabled the S . cerevisiae mutant to utilize both sucrose and maltose . DNA sequence analysis revealed that CASUC1 encodes a putative zinc finger-containing protein with 28% identity to a maltose-regulatory gene (MAL63) of S . cerevisiae . The gene products of CASUC1 and MAL63 are approximately the same size (501 and 470 amino acids, respectively), and each contains a single zinc finger located at the N terminus . The zinc fingers of CASUC1 and MAL63 comprise six conserved cysteines (C6 zinc finger) and are of the general form Cys-Xaa2-Cys-Xaa6-Cys-Xaavariable-Cys-Xaa2-Cys-+ ++Xaa6-Cys (where Xaan indicates a stretch of the indicated number of any amino acids) . Both contain five amino acids in the variable region . CASUC1 also complemented the maltose utilization defect of an S . cerevisiae mutant (TCY-137) containing a defined mutation in a maltose-regulatory gene . The sucrose utilization defect of type II Candida stellatoidea, a sucrase-negative mutant of C . albicans, was corrected by CASUC1 . Determinations of alpha-glucosidase activity in whole cells revealed that activity was restored in transformants cultivated on either sucrose or maltose . To our knowledge, this is the first zinc finger-encoding gene, as well as the first putative regulatory gene, to be identified in C . albicans. Infect Immun, 1992 Jan, 60(1), 213 - 8 Arg-Gly-Asp (RGD) peptides alter hepatic killing of Candida albicans in the isolated perfused mouse liver model; Sawyer RT et al.; The isolated perfused mouse liver model was used to study the effect of Arg-Gly-Asp (RGD)-containing peptides on hepatic trapping and killing of Candida albicans . After extensive washing, 10(6) C . albicans CFU were infused into mouse livers . At the time of recovery, 63% +/- 2% (mean +/- standard error of the mean) of the infused C . albicans CFU were recovered from the liver and 14% +/- 1% were recovered from the effluent for a total recovery of 77% +/- 2% . This indicates that 86% +/- 9% of the original inoculum was trapped by the liver and that 23% +/- 2% was killed within the liver . Prior to their infusion into livers, 10(7) CFU of C . albicans were incubated at 37 degrees C for 30 min in the presence of various RGD peptides (0.1 mg/ml) . Repeatedly, more than 90% of the infused RGD-treated C . albicans was trapped by the perfused liver . In comparison with the 23% killing rate observed in control livers, perfused livers killed approximately 40 to 50% of the infused C . albicans treated either with fibronectin, PepTite 2000, RGD, or RGDS . Hepatic killing of C . albicans treated with PepTite 2000 or fibronectin was dose dependent . Treatment of C . albicans with GRGDTP, GRGDSP, GRADSP, or GRGESP did not alter the ability of the perfused liver to kill C . albicans, suggesting that a degree of specificity for RGD peptides is associated with an increased ability of liver to kill RGD-treated C . albicans . Together, the data suggest that RGD peptides bind to a receptor on the surface of C . albicans, thereby increasing hepatic, and presumably Kupffer cell, killing of C . albicans . Natural or synthetic RGD peptides may serve as opsonins promoting C . albicans killing by Kupffer cells. Infect Immun, 1992 Jan, 60(1), 183 - 8 Biological activity of interleukin-2 bound to Candida albicans; Treseler CB et al.; The lymphokine interleukin-2 (IL-2), which is necessary for the generation of an optimal cell-mediated immune response, has recently been shown to have lectinlike properties, with specificity for high-mannose groups . Therefore, the ability of IL-2 to bind to the mannose-rich fungus Candida albicans was examined . Heat-killed fungi preincubated with IL-2 stimulated, in a dose-dependent manner, proliferation of the IL-2-dependent cell line CTLL20 . Soluble mannan, which is rich in exposed mannose groups, inhibited binding of IL-2 to C . albicans by approximately 60%, suggesting that the lectinlike properties of IL-2 are partially responsible for its fungal binding capacity . Binding of IL-2 to fungi appeared to be reversible, as C . albicans preincubated with IL-2 stimulated CTLL20 proliferation even when the fungi and cells were separated by an 0.4-microns-pore-size membrane . The lymphoproliferative response of normal human peripheral blood mononuclear cells to C . albicans was augmented when the fungus was preincubated with IL-2 . Binding of 125I-IL-2 could not be inhibited by unlabeled IL-2, suggesting the absence of high-affinity receptors on C . albicans for IL-2 . While the in vivo relevance remains to be determined, these data demonstrate that IL-2 can bind to C . albicans in vitro and thereby influence the host response to this medically important fungus. Jpn J Ophthalmol, 1992, 36(1), 23 - 7 Study of suppressive effect of intravenous fluconazole on endogenous Candida endophthalmitis in rabbits; Isobe Y et al.; The effect of intravenous fluconazole on endogenous Candida endophthalmitis in rabbits was investigated . Preventive and therapeutic experiments were carried out . In the preventive series, rabbits were injected intravenously with 5 mg/kg of fluconazole at 30 minutes, 1 day and 2 days after intravenous inoculation with Candida albicans spores . The control group received no medication . No treated rabbits developed ocular lesions and no Candida spores were isolated from the treated eyes . On the other hand, all control rabbits developed bilateral chorioretinitis and C . albicans was isolated invariably from the control eyes . In the therapeutic series, intravenous fluconazole (5 mg/kg body weight) was administered from 3 to 6 days after inoculation . All rabbits developed chorioretinitis and Candida spores were isolated from all eyes . Therefore, the results of this study prove that intravenous fluconazole is more effective in preventive use than in therapeutic use against endogenous Candida endophthalmitis in rabbits. Clin Lab Haematol, 1992, 14(2), 137 - 47 In vitro effects of ethanol on the phagocytic and microbial killing activities of normal human monocytes and monocyte-derived macrophages; Zuiable A et al.; Human blood monocytes were cultured within the wells of chamber slides in growth medium to which 0, 1, 2, or 3 mg ethanol per ml was added at the start of the culture . After incubation for 1 h, 1 day and 7 days, their ability to phagocytoze IgG-sensitized red cells and to phagocytoze and kill non-opsonized Candida albicans was assessed . In all alcohol-containing wells, the concentration of alcohol in the growth medium fell progressively, reaching negligible values after 3 days . When compared with control cells, monocytes incubated with 1, 2 or 3 mg ethanol/mg for 1 h showed impaired phagocytosis of IgG-sensitized RBC and non-opsonized C . albicans and those incubated with 1 or 2 mg ethanol/ml for 1 h showed impaired killing of Candida . After incubation for 7 days, the monocyte-derived macrophages in wells initially containing 1, 2 or 3 mg ethanol/ml showed increased phagocytic activity towards C . albicans but not towards sensitized RBC . In addition, in 4 of 5 experiments, the percentage of phagocytozed organisms killed was increased in wells initially containing 1 mg ethanol/ml . The results support the view that the susceptibility of chronic alcoholics to certain infections may be partly dependent on an ethanol-induced depression of the phagocytic and killing functions of macrophages . They also suggest that a few days after a brief period of exposure to ethanol there may be stimulation of certain but not all effector functions of macrophages. Chemotherapy, 1992, 38(1), 46 - 56 Subinhibitory concentration of octenidine and pirtenidine: influence on the lipid and sterol contents of Candida albicans; Ghannoum MA et al.; The effect of subinhibitory concentrations of octenidine and pirtenidine on the lipid and sterol composition of Candida albicans was investigated . The total lipid and sterol contents of C . albicans grown in the presence of either octenidine or pirtenidine were reduced compared with control-grown cells . The major differences in the lipid composition of drug-grown and control cells were phosphatidylglycerol, phosphatidylcholine and monogalactosyldiacylglycerol, which increased in the presence of octenidine and pirtenidine . Lower proportions of phosphatidic acid were found in yeasts grown in the presence of the drugs when compared with control C . albicans . Fatty acid analysis of control-grown cells showed that the major fatty acids were C16 and C18 . Drug-grown cells had higher proportions of palmitic and linolenic acids but lower proportion of oleic acid . The C16/C18 ratios were higher for octenidine- and pirtenidine-grown cells than control cells . Differences in the fatty acid composition of major phospholipids and neutral lipids between drug-grown and control yeasts were also observed . Sterol analysis of control-grown cells showed that the major sterol present was ergosterol (65.9%) . A significant increase in squalene and 4,14-dimethylzymosterol was observed in pirtenidine-treated cells, while octenidine-treated cells showed an increase in zymosterol and obtusifoliol contents . Our results suggest that octenidine and pirtenidine affect the lipids and sterol of C . albicans in different ways . The implications of these findings on the mode of action of these two drugs is discussed. Pediatr Radiol, 1992, 22(1), 68 - 9 An unusual CT presentation of congenital cerebral toxoplasmosis in an 8 month-old boy with AIDS; Taccone A et al.; We report on a 8-month-old boy with AIDS, born of an asymptomatic mother with positive HTLV-III serology . He was hospitalized in the Intensive Care Unit because of anemia, fever and hepatosplenomegaly . Chest X-ray showed pneumonia and subsequent blood cultures were positive for Candida albicans . After 3 days of Amphotericin B treatment, the patient was transferred to Infectious Disease Department . After 30 days of hospitalization, the patient developed a rapid neurological impairment evolving into coma . CT scan showed a round, ring-shaped low density lesion with hyperdense and enhancing haemorrhagic centre in the left basal ganglia and a smaller hypodense lesion on the right . There was also evidence of cortical atrophy and mild ventricular dilatation . Such lesions are more commonly described in children with AIDS and congenital cytomegalic inclusion virus (CMV) encephalitis . In this case toxoplasma cysts were shown microscopically reinforcing the contention that in patients with AIDS, toxoplasma gondii infection may occur with atypical manifestation. Eur J Appl Physiol Occup Physiol, 1992, 64(4), 323 - 7 Stimulation of the phagocytic function in guinea pig peritoneal macrophages by physical activity stress; Ortega E et al.; A study was made of all the different stages of the phagocytic function in peritoneal macrophages from male guinea pigs {3 (SD 1) months old} before, immediately after, and 24 h after being subjected to stress from physical activity (swimming until exhaustion) . The early (10 min) and late (40 min) adherence to tissue substrates, chemotaxis, attachment and phagocytosis of Candida albicans, ingestion of inert particles (latex beads), and basal oxidative metabolism {measured by nitroblue tetrazolium (NBT) reduction} were significantly stimulated by the physical activity . After 24 h, late adherence, attachment capacities, and basal oxidative metabolism returned to basal values, whereas early adherence, chemotaxis, phagocytosis of cells and inert particles, and microbicidal capacity (production of superoxide anion measured by NBT reduction in presence of ingested material) remained significantly increased . The stress produced by physical activity, reflected in increased serum corticosterone values, led to a global stimulation of the phagocytic function. Chemotherapy, 1992, 38(2), 112 - 7 In vitro susceptibility of yeast isolates from the blood to fluconazole and amphotericin B; Dermoumi H; 221 yeast strains including 131 of Candida albicans, 21 of C . tropicals, 23 of C . parapsilosis, 19 of C . glabrata, 7 of C . guilliermondii, 6 of C . krusei and of other species were isolated from the blood . The activity of fluconazole and amphotericin B was investigated by means of a photometer-read broth microdilution method measuring the 30% inhibitory concentrations (IC30) . The results of fluconazole showed a higher susceptibility of C . albicans compared to the other species . However, 6 (4.5%) resistant strains of C . albicans were found . Low sensitivity and resistance were evaluated for C . krusei and C . glabrata strains . All isolates showed susceptibility to amphotericin B. Antimicrob Agents Chemother, 1992 Jan, 36(1), 56 - 8 Efficacy of cilofungin therapy administered by continuous intravenous infusion for experimental disseminated candidiasis in rabbits; Rouse MS et al.; Cilofungin has potent in vitro activity against Candida albicans, but previous in vivo models using twice daily intermittent dosing regimens have not consistently demonstrated in vivo efficacy . Because of the pharmacokinetics of cilofungin in rabbits, it has been suggested that administration by continuous intravenous infusion might be more effective . We compared the in vivo efficacy of continuous intravenous infusion of cilofungin with that of amphotericin B in a rabbit model of disseminated candidiasis . Cilofungin prepared as previously described in phosphate-buffered 33% polyethylene glycol was lethal to infected rabbits in this model, as was phosphate-buffered 33% polyethylene glycol alone . In contrast, cilofungin in 26% polyethylene glycol and sterile water administered by continuous intravenous infusion was tolerated by rabbits, was significantly more effective than amphotericin therapy in reducing candida colony counts in kidney tissue, and was as effective as amphotericin therapy in lung and spleen tissue and in cardiac valvular vegetations . The dosage regimen and diluent used in some previous studies may have adversely affected outcome of treatment with cilofungin. Antimicrob Agents Chemother, 1992 Jan, 36(1), 132 - 6 Effect of an arginine-glycine-aspartic acid-containing peptide on hematogenous candidal infections in rabbits; Klotz SA et al.; The adherence of Candida albicans yeast cells to the subendothelial extracellular matrix, fibronectin, laminin, and type I and IV collagen was tested . Fibronectin (10(-7) M) and a peptide, PepTite-2000 (Telios Pharmaceuticals Inc., San Diego, Calif.), containing the sequence arginine-glycine-aspartic acid (RGD) inhibited Candida adherence to these targets by greater than 90% . When C . albicans was perfused over ex vivo rabbit aortic endothelium, there was no significant difference in the amount of adherence in the presence or absence of the RGD-containing peptide . However, the RGD-containing peptide reduced the number of Candida organisms present in liver, brain, heart, and kidneys (P less than 0.05) of rabbits 4 h after intravenous inoculation of 5 x 10(7) C . albicans yeast cells . The peptide also reduced the number of macroscopic Candida abscesses in the kidneys of rabbits 72 h after intravenous inoculation of 10(7) C . albicans yeast cells (P less than 0.05) . Inhibition of Candida adherence in vitro and in vivo may occur because the peptide blocks a fungal receptor that is necessary for adherence. Ann Nutr Metab, 1992, 36(1), 41 - 7 Impairment of phagocytic process in macrophages from young and old mice by protein malnutrition; de la Fuente M et al.; In young (15 +/- 2 weeks old) and old (75 +/- 5 weeks old) Swiss mice fed a 4% protein diet ad libitum for 15 days, we studied the different steps of phagocytic processes of peritoneal macrophages . In young mice, adherence to tissue substrates was significantly increased, but spontaneous mobility, chemotaxis, attachment and ingestion of opsonized Candida albicans, and production of superoxide anion indicative of microbicidal capacity measured by the nitroblue tetrazolium (NBT) reduction were significantly decreased with respect to the corresponding young controls (mice fed with a standard 17% protein diet) . Attachment and ingestion of C . albicans, and NBT reduction were also decreased in old protein-malnourished mice. J Acquir Immune Defic Syndr, 1992, 5(6), 610 - 8 Determination of salivary anticandidal activities in healthy adults and patients with AIDS: a pilot study; Pollock JJ et al.; This investigation compared the salivary anticandidal activities of 12 healthy adults with 12 hospitalized patients with AIDS . Stimulated parotid, submandibular-sublingual, and whole salivas were collected during a period of 10 min, immediately acidified, boiled, and then centrifuged to isolate salivary supernatants . Supernatants were then tested for antifungal activity against Candida albicans in blastospore viability inhibition and germ tube formation assays . A unit of blastospore or germ tube antifungal activity was established as that activity yielding 90% or greater inhibition during a defined time period in each salivary assay . Each of the patients with AIDS were found to be defective in one or more of their salivary antifungal activities, and in comparison with healthy adults the differences in antifungal units per milliliter of saliva and total antifungal units were statistically significant for each saliva and each antifungal assay . Defective salivary antifungal activity may contribute to the oral candidiasis seen in patients with AIDS. J Med Vet Mycol, 1992, 30(2), 123 - 31 A new, sensitive polynucleotide probe for distinguishing Candida albicans strains and its use with a computer assisted archiving and pattern comparison system; Wilkinson BM et al.; The repetitive DNA sequence poly{d(GT).d(CA)},(polyGT) can be used to generate DNA fingerprints that distinguish different yeast genera . In this study we demonstrate that the probe can also be used to distinguish individual strains of clinical isolates of Candida albicans . Isolates were fingerprinted by probing Southern blots of restriction enzyme-cleaved DNA samples with radioactively labelled polyGT . The discrimination between strains was clearer than can be achieved by direct visualization of ethidium bromide stained gels and was comparable to that achieved with previous DNA probes . However, the advantage of this probe is that it is not limited to Candida species since polyGT sequences appear to be ubiquitous in eukaryotes . Fingerprints were also generated from Southern blots using a commercial (AMBIS) radioanalytical imaging computer system . A proprietary software package (MICRO PM) was effective in discriminating between the C . albicans strains . These preliminary results indicate the potential value of this probe for discrimination between Candida isolates in epidemiological studies of candidosis. J Med Vet Mycol, 1992, 30(2), 105 - 14 Occurrence and biochemical characterization of GTP-binding proteins in Candida albicans; Nagata K et al.; The activities of GTP-binding and GTPase in Candida albicans were present in the cytosol, KCl- and cholate-extractable fractions . At least two kinds of GTP-binding proteins were found in the cytosolic fraction; the major one with a molecular mass of about 30 kDa and the other about 500 kDa . The former specifically bound guanine nucleotides and was most likely to bind GDP since guanosine 5'-O-(thio) triphosphate (GTP gamma S)-binding was accelerated by addition of (NH4)2SO4 . The latter showed no specificity in nucleotide binding and could also bind adenine nucleotides . The proteins were not ADP-ribosylated by either pertussis toxin or cholera toxin . These results indicate that ras-like monomeric, low molecular mass GTP-binding proteins distinct from heterotrimeric G proteins such as Gi, Go and Gs are present in C . albicans. Langenbecks Arch Chir, 1992, 377(2), 89 - 93 {Prognostic factors in diffuse peritonitis}; Barthlen W et al.; In order to evaluate their prognostic relevance for survival 46 variables were submitted to univariate as well as multivariate analysis in a group of 184 patients with diffuse peritonitis . In the univariate analysis a significant correlation with the outcome was found for the following parameters: age greater than or equal to 70 years, preexisting hepatic or cardiac disease, no eradication of the primary source of infection at first laparotomy for peritonitis, cardiovascular instability, respiratory failure, hyperbilirubinemia, thrombocytopenia, elevated serum creatinine and diminished creatinine clearance at the beginning and proof of pseudomonas aeruginosa in the peritoneal exsudate and of candida albicans in the blood culture during the course of the peritonitis . In the multivariate analysis the surgical eradication of the primary source of infection at the first laparotomy for peritonitis, serum creatinine at the beginning of peritonitis, age greater than or equal to 70 years and a preexisting hepatic disease proved to be the independent variables with significant prognostic relevance for survival of the patients. Int J Biochem, 1992, 24(1), 145 - 9 The lysine analog L-oxalysine is an inhibitor of RNA synthesis; Zheng H et al.; 1 . The lysine analog L-4-oxalysine was found to be a potent inhibitor of RNA synthesis in Candida albicans . 2 . The compound was a weak inhibitor of protein synthesis and DNA synthesis was not affected . 3 . The inhibition of RNA synthesis was reversed by L-lysine but not D-lysine . 4 . The decrease in the level of newly synthesized RNA in cells treated with L-oxalysine was due to inhibition of de novo synthesis rather than to degradation of RNA. Clin Infect Dis, 1992 Jan, 14(1), 340 - 7 Fungal adherence to the vascular compartment: a critical step in the pathogenesis of disseminated candidiasis; Klotz SA; The importance of adherence of Candida albicans to the vascular structures in the pathogenesis of disseminated candidiasis is discussed . The evidence for adherence of this fungus to endothelial cells and to the subendothelial basement membrane in vivo is reviewed, as are the data documenting these events in vitro . Information on the subcellular interactions of the host's vascular structures with this pathogen is presented . For example, the C . albicans surface receptors for iC3b, laminin, and fibronectin are discussed in light of their possible ability to mediate the adherence of the fungus to vascular structures . The review is concluded with a potentially unifying concept of integrin-like receptors on Candida that bind arginine-glycine-aspartic acid-containing peptides that may account for the binding of numerous human proteins to C . albicans. Retina, 1992, 12(1), 46 - 51 Intravitreal corticosteroids in the treatment of exogenous fungal endophthalmitis; Coats ML et al.; A rabbit model of exogenous Candida albicans endophthalmitis was used to determine if intravitreal corticosteroids combined with an efficacious antifungal agent enhanced fungal proliferation and ocular destruction, or if the combination can suppress the inflammatory and immunogenic response that causes retinal and uveal destruction . Exogenous Candida albicans endophthalmitis was experimentally induced in 20 rabbit eyes . Eight eyes received intravitreal amphotericin B alone; eight eyes received amphotericin B plus dexamethasone . Four eyes served as controls . By clinical grading on the fourth day after infection, the vitreous of the eyes in the two drug-treated groups was significantly clearer in comparison to that of eyes in the control group . By the seventh day after infection, the eyes treated with amphotericin B plus dexamethasone had significantly clearer vitreous in comparison to the eyes receiving only amphotericin B (P = 0.0017) . Quantitative culture results were negative in both treatment groups, and histopathologic examination confirmed the clinical grading . Contrary to current beliefs, there was no evidence that the addition of corticosteroids impaired antifungal activity or enhanced fungal proliferation. Eur J Clin Microbiol Infect Dis, 1992 Jan, 11(1), 22 - 6 Effect of cilofungin on phagocytosis and intracellular killing of Candida albicans by human neutrophils; Richardson MD et al.; The effect of a beta glucan synthase inhibitor, cilofungin, amphotericin B and 5-fluorocytosine on opsonization, phagocytosis and intracellular killing of Candida albicans blastospores by glass-adherent human neutrophils was determined by microscopy and dye exclusion staining . Pretreatment of blastospores for 2, 4, 6 and 18 h with 1.25 mg/l cilofungin resulted in 24-28% of neutrophils ingesting compared to 24% with no drug present . There was no significant difference in the phagocytic index with increased incubation time . Percentage ingestion and phagocytic index values were not significantly different when blastospores were pretreated for 2 h in the presence of 3, 7, 15, 31 and 62 mg/l cilofungin . Comparable concentrations of amphotericin B and 5-fluorocytosine gave similar results . In the absence of cilofungin, intracellular killing after 2 h was 54% . In the presence of 1 and 10 mg/l cilofungin, 85-90% of intracellular blastospores were killed . Therapeutic levels of amphotericin B or 5-fluorocytosine did not enhance intracellular killing . These data demonstrate the potentiation of intracellular killing of Candida albicans by neutrophils in the presence of cilofungin. Arerugi, 1992 Jan, 41(1), 7 - 14 {Studies on IgG subclass antibodies in adult asthma . 2 . Changes in serum antigen specific IgG subclass antibodies for aging and intractability in asthmatics}; Ogurusu K et al.; To clarify the factors which induce intractable asthma, the level of serum IgG subclass antibodies to mite (Dermatophagoides farinae) and Candida antigens (Candida albicans) for aging and severity was investigated in 230 bronchial asthmatics (Male: 117, Female: 113) aged 6-81 years old (mean age = 40) . Total IgE level and IgE antibodies to mite and Candida antigens were measured by radioimmunosorbent test (RIST) and radioallergosorbent test (RAST), respectively . The serum level of IgG and IgG1 antibodies to the antigens were measured by enzyme-linked immunosorbent assay (ELISA) . The results were as follows: 1) The incidence of severe asthma in aged and late onset asthmatics, especially late onset intractable asthma (LOIA), was higher than that in young and early onset asthmatics . 2) The serum level of total IgE and IgE antibodies to mite in aged and late onset asthmatics was lower than that in young and early onset asthmatics . 3) The incidence of severe and intractable asthmatics in the group of low IgE levels (less than 300 IU/ml) was higher than that in the group of high IgE levels (over 500 IU/ml) . The incidence of positive IgE (RAST) score to mite in severe and intractable asthmatics was lower than that in mild and moderate asthmatics . 4) Considering aging, the serum levels of IgG and IgG1 antibodies to mite and Candida in severe and intractable asthmatics was higher than those in mild asthmatics . These data indicate that the aged and late onset asthmatics may produce dominantly the IgG (IgG1) antibody to the antigens, and have severe asthma attacks caused by IgG (IgG1) rather than IgE antibody. Arerugi, 1992 Jan, 41(1), 49 - 55 {A case report of pulmonary infiltration with eosinophilia syndrome induced by Candida albicans}; Miyagawa H et al.; A sixty six-year-old female who had been treated for bronchial asthma for about 25 years was admitted to the hospital with complaints of episodes of dyspnea, eosinophilia and infiltrative shadows in the chest X-ray film . An infiltrative shadow appeared to move from the left to the right lung field and finally formed a shadow of atelectasis in the middle field of the right lung . A sputum culture showed only Candida albicans . Allergic and immunologic examination revealed high IgE serum levels with specific IgE against Candida albicans in high titer, and Aspergillus fumigatus in low titer . The precipitating antibody was shown only against Candida antigen . Additionally, the blastogenic response to Candida antigen was high in comparison with other fungal antigens including Aspergillus fumigatus . The clinical features and laboratory findings of this patient were found to satisfy Rosenberg's criteria for allergic bronchopulmonary aspergillosis (ABPA), except for the existence of Candida albicans in place of Aspergillus species as the causative antigen . The pathogenesis of PIE syndrome has been studied and various allergic mechanisms against many antigens reported . In this patient Candida albicans could be playing the crucial role in the formation of PIE syndrome, which might be best described as allergic bronchopulmonary candidiasis (ABPC). Indian J Gastroenterol, 1992 Jan, 11(1), 21 - 2 Cimetidine therapy and duodenal candidiasis: role in healing process; Singh S et al.; Patients with Candida colonization and invasion were studied in 20 duodenal ulcer (DU) patients, 10 non-ulcer dyspepsia (NUD) cases and 10 controls with non-gastroenterological disorders . Of 20 DU patients, Candida albicans was cultured from duodenal aspirates of 6 (30%) DU patients and pseudohyphae, indicating invasive form, were present in two (10%) prior to treatment . NUD patients and controls had positive Candida culture in 3 (30%) and 1 (10%) cases respectively; pseudohyphae were found in none . Six DU patients (30%) failed to heal with 4 weeks of cimetidine therapy; all six showed invasion of duodenal ulcer mucosa with Candida on histology . The pseudohyphae form of Candida was always found to be associated with non-healing of DU . Candidal invasion is associated with failure to respond to, H2-receptor antagonist therapy. Dermatology, 1992, 184 Suppl 1, 8 - 17 Influence of amorolfine on the morphology of Candida albicans and Trichophyton mentagrophytes; Muller J et al.; Amorolfine applied in concentrations of 0.1-100 micrograms/ml causes considerable damage to the ultrastructure of Candida albicans and Trichophyton mentagrophytes: electron-lucent areas appear in the cytoplasm . Extracytoplasmic membrane vesicles are formed and deposited in the cell wall . Starved fungal cells, with normal ultrastructure, can be found . Lysed, dead cells demonstrate the process of severe ultrastructural damage . T . mentagrophytes cell walls especially increase in thickness . The feature of the damage caused by amorolfine is comparable to that produced by azole antifungals. J Ethnopharmacol, 1992 Jan, 35(3), 275 - 83 Screening for antimicrobial activity of crude drug extracts and pure natural products from Mexican medicinal plants; Rojas A et al.; Preliminary antimicrobial screening against Candida albicans and selected Gram-positive and Gram-negative bacteria of methanol extracts prepared from eight Mexican medicinal plants, noted for their antiseptic properties, was conducted . The significant activity exhibited for extracts of Ratibida latipalearis, Teloxys graveolens, Dodonaea viscosa, Hyptis albida, H . pectinata, H . Suaveolens and H . verticillata tends to support their traditional use as anti-infective agents . Only the extract of Hintonia latiflora was inactive . The antimicrobial activities of 44 pure natural compounds and two derivatives were determined . Of these, only 23 compounds were effective in inhibiting the growth of the tested organisms (MIC less than or equal to 100 micrograms/ml). J Prosthet Dent, 1992 Jan, 67(1), 72 - 7 Assessment of antimicrobial treatment of denture stomatitis using an in vivo replica model system: therapeutic efficacy of an oral rinse; Lal K et al.; Five denture stomatitis patients demonstrating Candida albicans on both maxillary dentures and palates volunteered to test the effects of Peridex oral rinse in treating their oral disease . They used Peridex rinse both as a mouthrinse and as a denture soak for a period of 24 days . Agar replicas of the tissue-fitting surfaces of the maxillary dentures revealed elimination of C . albicans . Significant decreases in palatal inflammation were also noted, although some inflammation was still evident . Several weeks after the termination of Peridex oral rinses, inflammation increased as concentrations of C . albicans on the denture surface returned to pretreatment levels . A marked similarity in the site-specific localization of this yeast species on the denture was noted before and after Peridex rinse treatment. Rinsho Ketsueki, 1992 Jan, 33(1), 82 - 6 {Percutaneous transhepatic intraportal administration of amphotericin B to a patient with multiple liver abscesses due to Candida albicans: with monitoring by fungal index as a parameter of Candida volume}; Murayama T et al.; A 59-year-old female with acute promyelocytic leukemia in remission was admitted to our center because of an episode of incidental high fever with general fatigue . She was found to have hepatomegaly . Abdominal CT revealed multiple liver abscesses and a positive culture was obtained for candida albicans from an aspirated abscess . She was treated with percutaneous transhepatic intraportal administration of amphotericin B in addition to oral and intravenous administration . We confirmed the remission of these abscesses by means of the fungal index which is the difference between the values of the limulus test and endotoxin specific test . The fungal index appears to be useful for early diagnosis and treatment of fungal infection. AIDS, 1992 Jan, 6(1), 81 - 4 Molecular typing of candida albicans isolated from oral lesions of HIV-infected individuals; Powderly WG et al.; OBJECTIVE: To evaluate the epidemiology of Candida albicans infection in HIV-infected patients with oral lesions using molecular techniques . METHODS: Thirty-nine isolates from HIV-positive patients with oral candidiasis were examined using two DNA probes (a Histoplasma capsulatum ribosomal DNA probe that cross-hybridizes with C . albicans and a C . albicans strain-specific probe derived from repetitive sequence DNA) . C . albicans obtained from the oral cavity of patients receiving cytotoxic chemotherapy was used as controls . RESULTS: Using the H . capsulatum ribosomal DNA probe, isolates were shown to members of many distinct classes of C . albicans . Forty-nine per cent (19 out of 39) of isolates were members of the same class; however, 46% (6 out of 13) of control C . albicans isolates were also members of this class . Further analysis of the class-restricted isolates from the HIV-infected patients using the C . albicans strain-specific probe showed that these could be further separated into distinct strains . CONCLUSIONS: These data indicate that strains of C . albicans that cause oral candidiasis in HIV-positive individuals are not clonally restricted and are similar to those colonizing the oral cavity of other severely immunocompromised hosts . Most patients appear to be infected with unique strains of C . albicans. Arch Dis Child, 1992 Jan, 67(1 Spec No), 48 - 52 Candida strains from neonates in a special care baby unit; Sharp AM et al.; Carriage and acquisition of Candida spp and Candida albicans biotypes were studied among 163 neonates and 90 staff in a neonatal intensive care and surgical unit during a 17 week period . Twenty one neonates carried yeasts in the mouth, rectum or groin when first sampled, and a further 25 were positive later . C albicans accounted for 94.7% of 431 yeast isolates from neonates but only 67.4% of 43 isolates from staff . The first isolated C albicans biotype persisted in 13 babies monitored longitudinally . Simultaneous colonisation with two Candida spp was found in 2/46 neonates and 5/33 staff . The prevalence of candida was significantly higher among babies of gestational age less than 28 weeks (65%) than those of higher gestational age (26%) . Oral and/or crural candida infection was observed in 14 of the babies but none developed deep seated candidosis . Routine antifungal prophylaxis did not affect the frequency of yeasts among the neonates. Med Microbiol Immunol (Berl), 1992, 181(3), 117 - 26 Flow cytometric assay for estimating fungicidal activity of amphotericin B in human serum; Martin E et al.; We describe a simple and rapid bioassay for estimating fungicidal activity of Amphotericin B in human serum using flow cytometry . The method exploits the fact that Candida albicans damaged by Amphotericin B show a decrease in size and take up propidium iodide to exhibit a red fluorescence after deoxycholate treatment . These phenomena display characteristic dose dependencies, and their assessment permits serum fungicidal activity to be broadly grouped into three categories: (1) subfungicidal; (2) fungicidal; and (3) strongly fungicidal . In normal human serum, these three categories correspond to Amphotericin B concentrations of 0 less than or equal to 0.5 micrograms/ml, 0.75-1.5 micrograms/ml, and greater than 2 micrograms/ml, respectively . Pilot analysis of serum samples obtained from four patients undergoing Amphotericin B therapy confirmed the feasibility of using the flow cytometric assay for estimating drug fungicidal activity ex vivo . The method is very simple, generates results within 5 h, and could prove useful for monitoring therapy with this effective but toxic drug. J Asthma, 1992, 29(5), 343 - 8 An increased level of specific IgG4 antibodies against Candida albicans in patients with bronchial asthma; Tanizaki Y et al.; Specific IgG4 antibodies against Candida albicans in sera were measured in 76 asthmatics . The increased level of specific IgG4 was found in cases 10-40 years old sensitive to house dust mite and/or Candida albicans, in cases with steroid-dependent intractable asthma (SDIA) and in elderly cases . The frequency of SDIA was the highest in cases 41 to 60 years old with higher frequency of increased IgG4 antibodies . The results show that specific IgG4 increases in relation to IgE-mediated immune response, long-term steroid therapy, and aging . All of these conditions may induce depressed cell-mediated immunity. J Med Vet Mycol, 1992, 30(3), 219 - 31 Fatal systemic candidiasis of gastrointestinal origin: an experimental model in mice compromised by anti-cancer treatment; Sandovsky-Losica H et al.; An experimental model of fatal systemic candidiasis originating from the gastrointestinal (GI) tract of compromised mice is presented . ICR female mice were compromised by a single anti-cancer treatment: irradiation (4 or 6 Greys i.e . 400-600 rads), methotrexate (MTX) (3 mg per mouse, intraperitoneally) or 5-fluorouracil (5FU) (200 mg kg-1, intravenously) . Three days later, compromised and non-treated control mice were exposed to Candida albicans administered orally . Morbidity and mortality due to candidiasis were monitored for 30 days post-candidal inoculation . Increased and longer GI colonization was noted among the MTX and 5FU treated mice, or 6 Greys irradiated mice (up to 92.3% for over 30 days in anti-cancer treated mice) . The stomach was found to be the major part of the GI tract involved in fungal colonization . A significant number (53.8-83.3%) of the anti-cancer treated mice developed systemic candidiasis originating from the GI tract, which was fatal in 30-80% of the infected animals . In systemically infected animals, candidal antigen was demonstrated in the serum, and fungal abscesses containing C . albicans were observed in the liver, kidneys and spleen . C . albicans was isolated from the infected organs . The severity of the infection, as reflected by the number of fungi in visceral organs, and by mortality during the 30 days post-candidal inoculation, indicated differences in the course and nature of the infection among the three treatment groups (i.e . MTX, 5FU, 6 Greys).(ABSTRACT TRUNCATED AT 250 WORDS) J Med Vet Mycol, 1992, 30(3), 197 - 206 Synergistic postantifungal effect of flucytosine and fluconazole on Candida albicans; Mikami Y et al.; The in vitro efficacy of flucytosine and fluconazole, separately and in combination, with respect to induction of a postantifungal effect (PAFE) on Candida albicans was studied . PAFE refers to the persistent suppression of fungal cell growth following a short period of exposure to an antifungal agent . A turbidometric method was used to measure cell growth and to quantitate the PAFE following exposure of C . albicans yeast cells to different concentrations of the two agents for 2 h . The PAFE was determined by the difference in time (h) required for growth of the control and test cultures to increase to the 0.5 absorbance level following removal of the drug by dilution . Minimum (MIC) and fractional inhibitory concentration determinations were made and the data used for selecting the concentrations used in the PAFE evaluations . A synergistic interaction of the two drugs at concentrations well below their individual MICs was evidenced . Flucytosine:fluconazole ratios of 1:16-1:32 at concentrations ranging from 0.024-0.098 micrograms ml-1 and from 0.78-1.56 micrograms ml-1, with flucytosine and fluconazole, respectively, induced PAFEs which persisted for 2.5 h longer than those achieved when each of the two agents was assayed separately. Microbiol Immunol, 1992, 36(5), 517 - 21 Augmentation of host resistance to Candida albicans infection in ascites tumor-bearing mice; Okawa Y et al.; We found that the number of peripheral blood polymorphonuclear leukocytes (PMN) dramatically increased in both sarcoma 180 (S-180) and MM-46 mammary carcinoma (MM-46) ascites tumor-bearing mice, and mice required a remarkable resistance to Candida albicans infection via intravenous route . When the resistance was determined by number of cells of C . albicans in the kidney, a significant decrease in the number of fungal cells was observed in the kidneys of infected ascites tumor-bearing mice . An increase of active oxygen levels of PMN from ascites tumor-bearing mice was observed, suggesting that this factor is important in developing of resistance in ascites tumor-bearing mice . Additionally, a culture supernatant of tumor cells co-cultivated with bone-marrow cells in vitro increased the number of granulocytes and macrophages differentiated from the bone-marrow cells. J Acquir Immune Defic Syndr, 1992, 5(9), 904 - 14 Pilot study comparing the salivary cationic protein concentrations in healthy adults and AIDS patients: correlation with antifungal activity; Lal K et al.; This investigation compared the salivary cationic protein concentrations of 12 healthy adult controls with those of 12 hospitalized patients with AIDS . Salivas were quantified by capillary electrophoresis using purified cationic protein standards . In parotid saliva, histidine-rich polypeptides (HRPs) 1-6, histatin 6, and lysozyme concentrations were determined . In addition to these eight cationic proteins, submandibular-sublingual saliva was also quantified for histatin 2 and the histatin 2 degradation product . When comparisons were made on the basis of individual proteins, the HRP-histatin concentrations in the AIDS patients showed either statistically significant decreases or a decreasing trend compared with healthy adult controls . When HRP-histatin concentrations were summed for each patient, there were statistically significant differences between the healthy adult controls and the individuals with AIDS in both parotid and submandibular-sublingual salivas . Closer examination revealed that some individuals with AIDS had HRP-histatin concentrations that fell within the normal range of the healthy adult controls . For these individuals, lower than expected salivary antifungal values were obtained . Either decreasing histidine-rich protein concentrations and/or an inability of these proteins in saliva to interact with Candida albicans may contribute to the defective salivary antifungal activity seen in AIDS patients. Chemotherapy, 1992, 38(3), 174 - 8 Saperconazole: in vitro and in vivo anticandidal activity; Fu KP et al.; The in vitro activity of saperconazole against eight candidal species (81 strains) was determined and compared with fluconazole, Sch 39304 and amphotericin B . Using brain heart infusion broth with an inoculum of 10(4) CFU/ml, the MIC ranges (micrograms/ml) of saperconazole were: less than or equal to 0.015- greater than 32 for Candida albicans, less than or equal to 0.015-16 for C . tropicalis, less than or equal to 0.015-32 for C . glabrata, less than or equal to 0.015-32 for C . parapsilosis, less than or equal to 0.015-0.12 for C . guilliermondii and less than or equal to 0.015-0.06 for C . krusei . Saperconazole was the most active agent tested against Candida species . Saperconazole and 5-fluorocytosine combinations showed synergistic interactions against Candida species, and no antagonistic interaction was demonstrated . In a rat vaginal candidiasis infection model, saperconazole and fluconazole were equipotent producing 75-100% cures at levels of 0.016-0.25%, respectively, when dosed intravaginally . After single oral dosing, saperconazole was 5-fold more potent than fluconazole with an ED50 value of 0.53 mg/kg . These data demonstrate that saperconazole is effective in a rat vaginal candidiasis infection either with a single oral dose or by intravaginal treatment. Allergol Immunopathol (Madr), 1992 Jan-Feb, 20(1), 35 - 9 {Immunologic clinical evaluation of a biological response modifier, AM3, in the treatment of childhood infectious respiratory pathology}; Sanchez Palacios A et al.; To assess the immunoclinical effectiveness of a biological response immunomodulator, we used AM3 (glycophosphopeptide ), a glucomannan polysaccharide extracted from the cell wall of a strain of Candida utilis, in 20 children with asthmatic bronchitis . They received 2 envelopes (1 g) daily for 4 months . The results were compared with a control group of 20 untreated children with the same pathology . The following clinical and immunological parameters were assessed in all of them: cough, dyspnea, expectoration, frequency and intensity of the bronchospasm, time of administration of the symptomatic medication, and the delayed cutaneous cells response by means of the intradermal reaction of 5 antigens (Trichophyton, Candida albicans, tuberculin, E . coli and bacterial antigens) . In the treated group, the immunoferon (AM3) reduced the symptoms, the intensity and frequency of the bronchospasm, and the symptomatic medication (table I, II and III) . In basal conditions, the 40 children presented a state of 75% anergy; after 4 months of treatment, the treated group experienced a 45% decrease in their anergic situation, variation which was statistically significant when compared with the control group . In our 20 treated patients, AM3 behaved like and immunostimulant, improving the clinical situation and progress in patients with infectious respiratory disorders . We consider that the immunoferon constitutes a coadjuvant therapy to bacterial immunotherapy. Zentralbl Mikrobiol, 1992, 147(1-2), 65 - 70 Enzymatic production of alpha-aminoadipate-delta-semialdehyde and related compounds by lysine epsilon-dehydrogenase from Candida albicans; Hammer T et al.; L-Lysine epsilon-dehydrogenase {L-lysine:NADP+ oxidoreductase (epsilon-deaminating), EC 1.4.1.15} of Candida albicans was studied emphasizing its application for the production of alpha-aminoadipate-delta-semialdehyde and related compounds . A high enzyme level (240 pkat/mg of protein in the crude extract) could be attained during growth in the presence of L-lysine as sole nitrogen source . After optimization of the reaction conditions a partial purified enzyme (1.5 nkat/mg of protein) was used to produce alpha-aminoadipate-delta-semialdehyde, S-(beta-acetaldehyde)-cysteine, alpha-amino-delta-hydroxyadipate-semialdehyde and alpha-amino-gamma-hydroxyadipate-semialdehyde from the corresponding substrates lysine, S-(beta-aminoethyl)-cysteine, 5-hydroxylysine and 4-hydroxylysine, respectively . After purification of the compounds using Dowex 50 x 4 chromatography a yield of the products between 4.6 and 6.8% was achieved. Microbiol Immunol, 1992, 36(11), 1207 - 16 cDNA cloning of an aspartic proteinase secreted by Candida albicans; Mukai H et al.; cDNA of an aspartic proteinase secreted by Candida albicans No . 114 was isolated using the polymerase chain reaction (PCR) . The primary structure of the enzyme was deduced from the nucleotide sequence of the cDNA and compared with the structures of Saccharomyces cerevisiae proteinase A and vacuolar aspartyl proteinase of C . albicans . The mature aspartic proteinase consisted of 341 amino acid residues, and was 17.6 and 15.3% identical with the proteinase A and the aspartyl proteinase, respectively . Two active aspartic acid sites and the amino acids near those sites were conserved in the aspartic proteinase . We also showed that there is another gene of aspartic proteinase than that of strain ATCC10231 reported by Hube et al (J . Med . Vet . Mycol . 29 (1991)) in the same C . albicans genome, both in that strain and in No . 114. Microbios, 1992, 72(292-293), 183 - 201 Evaluation of the genotoxic spectrum of cisplatin for Candida albicans; Sarachek A et al.; The platinum co-ordination complex cisplatin {cis-diamminedichloroplatinum (II)} is a highly effective anticancer drug whose activity derives from its ability to form adducts crosslinking neighbouring purine bases in DNA . Under in vitro conditions, cisplatin induced cellular inactivation, forward and reverse mutations, reciprocal and nonreciprocal mitotic recombinations and phenotypic switching in the opportunistically pathogenic yeast Candida albicans . Mutant and recombinant yields were higher with post-treatment growth at 25 degrees C rather than 37 degrees C: the reverse was true for cell death or phenotypic switches . These responses comport with prior evidence that, generally, the higher recovery temperature discourages DNA repair processes in C . albicans . Thiosulphate, an agent used therapeutically to reduce nephrotoxic side effects of cisplatin in humans, greatly decreased both the lethality and recombinagenicity of cisplatin for C . albicans . Implications of these observations for possible genetic destabilization of C . albicans populations born naturally by cancer patients undergoing treatments with cisplatin are discussed. Zh Mikrobiol Epidemiol Immunobiol, 1992, (9-10), 18 - 21 {Spontaneous variability in a population of Candida albicans strains}; Karaev ZO et al.; The spontaneous variability of the populations of C . albicans strains of different genesis in the morphological properties of their colonies and in the potential of the activity of their extracellular proteolytic and phospholipid enzymes has been studied . The isolated types of colonies, differing in their morphology, have the phenotypic character of variability . Different populations of strains exhibited variability in the activity of enzymes, depending on morphological variants isolated from these populations . Selected morphological variants with high potential of their proteolytic enzymes retained stability in this property for 5 generations and can be used in medical practice for the isolation of C . albicans antigens. Autoimmunity, 1992, 13(4), 285 - 90 Does mitogen-induced antibody production by normal blood cells mimic spontaneous production in lupus? Dar O, Salaman MR, Seifert MH, Isenberg DA. Blood cells from patients with systemic lupus erythematosus (SLE) showed a raised level of spontaneous IgG production that included antibodies to DNA and to common environmental antigens (influenza virus haemagglutinin, adenovirus hexon and mannan from Candida albicans) . In contrast, no IgG antibody was produced against an antigen not normally encountered in the UK (egg antigen from Schistosoma mansoni) or a self-antigen not generally associated with SLE (thyroglobulin) . IgM production was raised to a lesser extent and only antibodies to DNA were detected . When normal cells were stimulated with pokeweed mitogen or S . aureus organisms, the specificity pattern of IgG production was similar to that described above for SLE with the major exception of the absence of IgG anti-DNA . IgM antibodies to DNA and all the other antigens were detected, but the specificity of the IgM ELISA assays for the protein antigens needs further clarification . The activity of IgM anti-DNA relative to total IgM was far greater in the SLE system . These results provide further evidence that a response to self-antigen is required for production of pathogenic IgG autoantibodies in SLE. Ann Pharm Fr, 1992, 50(2), 103 - 11 {Synthesis and structure of substituted bromo and nitrobenzyl benzylidene imidazolidinediones and thiazolidinediones}; Amorim EL et al.; Synthesis and physico-chemical properties of five bromobenzyl-benzylidene-imidazolidinediones and five nitrobenzyl- or benzyl-benzylidene-thiazolidinediones are described . The microbiological activity of bromobenzyl-benzylidene-imidazolidinediones against microorganisms such as Candida albicans, Neurospora crassa and Mycobacterium smegmatis are evaluated. J Med Vet Mycol, 1992, 30(5), 369 - 76 Glucan synthesis and its inhibition by cilofungin in susceptible and resistant strains of Candida albicans; Angiolella L et al.; The lipopeptide antimycotic agent, cilofungin, at a dose of 20 micrograms ml-1, inhibited beta 1-3 glucan synthesis in a drug-susceptible strain (3153; minimum inhibitory concentration (MIC) < 1 microgram ml-1) as well as in a drug-resistant strain of Candida albicans (CA-2, derived from 3153 by nitrosoguanidine mutagenesis; MIC > 50 micrograms ml-1) . This was demonstrated for both whole cells under growing and non-growing conditions, and during protoplast regeneration . However, time-effect experiments, during growth of a CA-2 culture initially exposed to an inhibitory dose of cilofungin, showed that this strain was able to progressively regain both glucan synthesis and a growth rate comparable to that of cultures that had not been treated with the drug . This recovery was not attributable to cilofungin instability or degradation within the CA-2 culture . Our study suggests the existence of an as yet unknown drug-related and/or cell-related factor(s) modulating the inhibition of glucan synthesis, and then contributing to the actual inhibitory effects of cilofungin in C . albicans. J Med Vet Mycol, 1992, 30(5), 363 - 7 Activity of fluconazole against Candida albicans isolates from HIV+ patients in a digestive candidosis turkey model; Reynes J et al.; Fluconazole activity against four strains of Candida albicans (three isolates from AIDS patients and one azole-resistant isolate, NCPF 3363) was studied in a turkey crop infection model . Isolate NCPF 3363 showed confirmed azole resistance in vitro and in vivo . Two isolates from AIDS patients were susceptible to fluconazole in vitro and in vivo . The third isolate was resistant to fluconazole in vitro (MIC = 100 micrograms ml-1), insensitive to 2.5 mg kg-1 but sensitive in vivo to a 5 mg kg-1 daily dose. J Med Vet Mycol, 1992, 30(5), 355 - 62 Phospholipid composition and subcellular distribution in yeast and mycelial forms of Candida albicans; Goyal S et al.; Lipids were found to constitute 3.9% and 4.7% of the dry weight of yeast and mycelial forms of Candida albicans, respectively . Phospholipids were localized mainly in the microsomal fraction of both growth forms and phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and cardiolipin were the major phospholipids . Myristic acid and palmitic acid were the predominant fatty acids in the yeast form while the mycelial form contained palmitic, palmitoleic and oleic acid as major fatty acids . Yeast forms showed significantly higher specific activities of intracellular phospholipase A and lysophospholipase when compared with mycelial forms . No significant difference in the specific activity of extracellular phospholipase A was seen in either morphogenic form while the activity of extracellular lysophospholipase was higher in the yeast form . These results are discussed in the context of the virulence of this fungus. Scand J Infect Dis, 1992, 24(5), 673 - 5 Candida albicans septicemia in a premature infant successfully treated with oral fluconazole; Bode S et al.; A premature male infant, birth-weight 1460 g, was treated successfully for a Candida albicans septicemia with orally administered fluconazole for 20 days . Dosage was 5 mg/kg/day . No side effects were seen . Fluconazole may present a major progress in treatment of invasive C . albicans infections in neonatology. Indian J Med Sci, 1992 Jan, 46(1), 1 - 6 Sporostatic effect of some oils against fungi causing otomycosis; Jain SK et al.; In vitro animycotic effect of mustard, groundnut, soybean, coconut and amla oils on five fungi i.e., Aspergillus niger, A . flavus, Absidia corymbifera, Penicillium nigricans and Candida albicans isolated from otitic fungal infection of external ear (Tympanic membrane) of human being was studied . Spore germination was evaluated in the oil samples as such after heating for two minutes & after boiling the oil . Data show that mustard and coconut oil seem to be effective as in these the spore germination was poor . Other oils were not found to be much effective . Sporostatic effect was noted only when the oils were used after heating or boiling this may be correlated by the synthesis of enzymes during spore germination. Cytobios, 1992, 70(281), 115 - 22 An ultrastructural evaluation of the reaction of the host cell membrane to the invasive phase of Candida albicans; Rajasingham KC et al.; Ultrastructural studies of the invasive form of Candida albicans in patients with acute or chronic candidosis have demonstrated either (a) a close seal between the host cell membrane and the fungal cell wall or (b) a ruptured or damaged host cell membrane at the point of invasion . This was observed in samples from either oral or vaginal candidosis as the pathogen successfully enters the adjoining host cell . The variations appear to be related to the degree of resistance of the host cell membrane to the invading pathogen . This view is discussed. Australas J Dermatol, 1992, 33(1), 45 - 8 Superficial mycoses in Saudi Arabia; Venugopal PV et al.; Between June 1988 and December 1990, 1018 cases of superficial mycoses were investigated . Diagnosis was confirmed by microscopic examination in 503 cases and the causal agent was isolated in 490 cases . Tinea capitis accounted for 47.7% (92.5% in children below 10 years of age) . The frequency of other clinical types in descending order was pityriasis versicolor 25.8%, tinea corporis 9%, onychomycosis 5.8%, tinea pedis 4%, intertrigo 3.9% and tinea cruris 2.8% . Erythrasma was encountered three times and mixed piedra and trichomycosis axillaris once . Microsporum canis was the commonest aetiological agent, responsible for 46.9% of ringworm infections . Malassezia furfur was the next most common agent (26.5%) followed by Candida albicans (8.6%) and Trichophyton violaceum (8.2%) . Other species were found less frequently . T.simii was isolated from four cases of tinea cruris and one each of tinea capitis and tinea corporis, and Piedraia hortae and Trichosporon beigelii from a case of mixed piedra infection. Ann Biol Clin (Paris), 1992, 50(2), 103 - 6 {Rapid identification of Candida albicans: evaluation of "Rapidec albicans" . Study of 444 yeast strains}; Fricker H et al.; Rapid identification of Candida albicans is of great importance as it is the most frequently isolated yeast pathogen . Rapidec albicans, a new 2-h micromethod, performs two fluorescent enzymatic activities: hexosaminidase and proline arylamidase . A total of 444 yeast strains (334 from type culture collections and 110 from recent clinical isolates) were tested . The sensitivity was 98.5% and the specificity 95.8% . When only considering the clinical strains, 47/47 Candida albicans were identified by Rapidec albicans (sensitivity 100%) but only 43/47 by the germ tube test (sensitivity 91.5%) . The specificities of the two tests were respectively 98.2% and 100% . This new system is therefore very efficient for the routine diagnosis of Candida albicans in the clinical field . It is easier and quicker than the germ tube test. J Med Vet Mycol, 1992, 30(4), 281 - 92 Immunoblotting analysis of sera from patients with candidal vaginitis and healthy females; Ishiguro A et al.; Antigenic components of Candida albicans were extracted from whole cells with a buffer containing SDS and 2-mercaptoethanol, and separated by SDS-polyacrylamide gel electrophoresis . The components reactive with IgG, IgA, IgM and IgE antibodies in sera from patients with (14 subjects) and without (15 subjects) C . albicans in the vagina, and from healthy females (34 subjects), were investigated by immunoblotting using immunoglobulin class-specific antibodies . Many components reacted with IgG and IgA in all sera tested; the major antigens that reacted strongly with the sera were 67, 62, 29 and 25 kDa components . Several components were observed which reacted with IgM in 63% of the sera; the 67, 62 and 25 kDa components that reacted with IgG and IgA also reacted with IgM . No components reacting with IgE were detected in any of the sera . No striking differences in antibody binding profiles to whole cell antigens were detected among the C . albicans positive and negative patients or the healthy subjects . On the other hand, IgG against extracellular proteinase was more frequently detected in the C . albicans positive patients than in the C . albicans negative group or the healthy subjects . This may suggest that vaginal infection with C . albicans contributes to a rise in anti-proteinase antibody levels. Folia Biol (Praha), 1992, 38(3-4), 263 - 8 Elevated IgA salivary antibody levels to mycobacterial 65 kDa stress protein in patients with oral candidosis; Ivanyi L et al.; Salivary IgA antibody levels to cytoplasmic protein extract of Candida albicans (CSE) and to mycobacterial 65 kDa stress protein (mSP65) were determined by ELISA in 25 patients with chronic atrophic oral candidosis and in 23 controls with clinically healthy oral mucosa . The results showed significantly elevated anti-CSE and anti-mSP65 antibody levels in patients when compared with healthy controls (P < 0.001) . A statistically significant relationship was found between salivary antibody titres to CSE but not to mSP65 and C . albicans colony counts in patients with oral candidosis. Eur J Clin Pharmacol, 1992, 43(2), 137 - 40 Comparison of salivary miconazole concentrations after administration of a bioadhesive slow-release buccal tablet and an oral gel; Bouckaert S et al.; The salivary miconazole concentrations after administration of a bioadhesive slow-release buccal tablet and an oral gel have been compared . The bioadhesive tablet consisted of a mixture of thermally modified starch and 5% polyacrylic acid . Although the amount of drug administered via the bioadhesive tablet was sixfold lower than when the gel was used, the salivary miconazole levels were higher and remained above the MIC value of Candida albicans for more than 10 hours . The mean adhesion time of the tablet was 586 min . The bioadhesive tablet appears to be a promising drug delivery system for the buccal administration of drugs for local therapy. Adv Exp Med Biol, 1992, 319, 193 - 200 Enhancement of host resistance to opportunistic infections by ubenimex (bestatin); Ishizuka M et al.; Ubenimex is a low molecular biological response modifier (BRM) which has been demonstrated to have antitumor and immunomodulatory activities . In this study, the effect of ubenimex on infection with Candida albicans was investigated in normal and immunosuppressed mice, and it showed a prophylactic effect . In normal mice, ubenimex prolonged survival time in a dose-dependent manner . In immunosuppressed mice treated with cyclophosphamide 4 days before infection, ubenimex at 5 mg/kg for 5 days significantly increased the number of survivors . Significant improvement in peritoneal leukocyte counts and in function of neutrophils including phagocytosis and release of activated oxygen was observed in ubenimex-treated mice . These results indicate that ubenimex is a potent BRM for prevention against opportunistic infections. Mycoses, 1992 Jan-Feb, 35(1-2), 9 - 16 Virulence of Candida albicans mutants; Polak A; Mutant strains of the fungal pathogen Candida albicans blocked in pyrimidine transport and salvage metabolism were tested for virulence in various animal models . The growth rate, germination and proteolytic enzyme production did not correlate with the virulence of the strains . However, a defect in the uridine transport system significantly decreased virulence in murine candidosis, although it had no effect in vaginal candidosis or in a Candida cyst model . It remains unclear whether this is due to the differing host defence mechanisms involved in systemic and superficial mycoses, or to the different requirements of the fungal systems for adherence and tissue invasion in the two types of infection. Mycoses, 1992 Jan-Feb, 35(1-2), 53 - 6 Susceptibility to ketoconazole of Candida albicans strains from sequentially followed HIV-1 patients with recurrent oral candidosis; Bruatto M et al.; The MIC values of the antifungal drug ketoconazole were evaluated on 66 Candida albicans strains . These strains were isolated from 26 HIV-1 infected patients with oral recurrent candidosis . Each episode of oral candidosis observed in these patients was orally treated with ketoconazole (200 mg/day) until the clinical disappearance of the lesions . The most frequent MIC values were 20 micrograms/ml and 10 micrograms/ml, observed in 37 and 19 isolates respectively . Only strains from five patients showed changes in their susceptibility to ketoconazole . This fact could indicate that a different strain causes the subsequent reappearance of the oral lesions, rather than the drug selecting resistant fungal strains . Our results stress the role of host characteristics in the occurrence of candidal infections, pointing to the progressing failure of the immunological response as the most important factor responsible for the recurrence of oral candidosis during HIV-1 infection. Mycoses, 1992 Jan-Feb, 35(1-2), 47 - 51 Candidaemia: a 10-year study in an Indian teaching hospital; Chakrabarti A et al.; Retrospective evaluation of candidaemia patients was performed in an Indian teaching hospital over a 10-year period . The incidence of patients with candidaemia increased eleven-fold in the second half of the study period (55 patients) compared with the first half (5 patients) . Haematological malignancies (11 patients), neonatal septicaemia (9), cardiac abnormalities and cardiac surgery (9) were the commonest underlying diseases in these patients . Candida albicans (50%), C . guilliermondii (17%), C . tropicalis (15%) and C . parapsilosis (8%) were the most common fungal pathogens isolated from blood culture . Therapy with two or more antibiotics (92%), corticosteroid administration (25%), intravascular catheter use for over 24 h (78%) and neutropenia (48%) were the accountable predisposing factors . Prolonged hospitalization (mean average 22.2 days as compared with 11.2 days in other patients) was an added risk factor in these patients. Invest Clin, 1992, 33(1), 33 - 7 {Serotyping of 48 isolates of Candida albicans: predominance of serotype A over B in Venezuela}; Mendoza M et al.; The study of serotyping of isolates of Candida albicans of clinical material obtained from different geographic areas of Venezuela suggest that serotype A is predominant over type B . These results are in relation with results obtained in other countries . Type A serotype is predominant in 57 to 100% in the areas studied . Only in 2 cities serotype B was isolated . Both serotypes of Candida albicans were observed in intertriginous, mucosal, inguinal and lung forms . These studies have allowed us to have information about the predominance of serotypes in certain areas of the country. Jpn J Antibiot, 1992 Jan, 45(1), 112 - 20 {Effects of KW-2228 on the function of polymorphonuclear neutrophils in rats for the phagocytosis and killing activity and the production of active oxygen}; Yoshitake H et al.; KW-2228 is a novel derivative of a recombinant human granulocyte colony-stimulating factor (rhG-CSF) with a modification . KW-2228 has some excellent properties such as high specific activity in stimulating granulocyte colony-formation in vitro, great biological stability in plasma, good pharmacokinetic profile and high potency in granulopoiesis in normal mice in vivo . In the present study, we investigated the effect of KW-2228 on phagocytic capacity and killing action of polymorphonuclear neutrophils (PMNs) obtained from normal rats which had been treated with KW-2228 using various microorganisms, such as Candida albicans, Escherichia coli and Pseudomonas aeruginosa . We also investigated the effect of KW-2228 on the production of superoxide anion using a luminol-chemiluminescence method . KW-2228 enhanced the phagocytosis and killing activity of PMNs of rats against C . albicans and E . coli . PMNs treated with KW-2228 showed some bactericidal activity against P . aeruginosa . These data obtained with PMNs treated with KW-2228 show a correlation between the bacterial susceptibility to phagocytosis and killing action and the lunimol-dependent chemiluminescence response . These results suggest the significance and the efficacy of KW-2228 used in an additional therapy to that of antibiotics in the treatment of infections diseases . KW-2228 is currently in Phase III clinical trials in Japan. Infect Immun, 1992 Jan, 60(1), 8 - 12 Expression of the C3d-binding protein (CR2) from Candida albicans during experimental candidiasis as measured by lymphoblastogenesis; Fukayama M et al.; The complement C3d-binding protein (CR2) of Candida albicans has been purified by immunoaffinity chromatography, and its specificity has been characterized by immunoblotting with monoclonal antibodies to the C . albicans CR2 and the mammalian CR2 . Recent studies with immunoelectron microscopy indicated that the CR2 was expressed during a systemic infection in a murine model of candidiasis . As a continuation of these observations, the immunogenicity of the C . albicans CR2 was investigated in a lymphoblastogenesis assay . Lymph node cells as well as splenic lymphocytes from mice infected subcutaneously with viable blastoconidia of C . albicans reacted to the C . albicans CR2 to a significantly greater extent than did lymphocytes from uninfected mice (P less than 0.01) . The maximum stimulation of splenic lymphocytes by the purified receptor occurred at a concentration of 0.54 micrograms of protein per ml after 72 h of incubation of lymphocytes and receptor . Also, splenocytes from infected or CR2-immunized mice exhibited significantly reduced responses to the T-cell-dependent mitogen phytohemagglutinin (P less than 0.01) . These data indicate that lymphocytes from infected mice respond to the C . albicans CR2 in a lymphoproliferation assay to a greater extent than do lymphocytes from uninfected mice, indicating that the CR2 is expressed in vivo. G Ital Chemioter, 1992 Jan-Dec, 39(1-3), 17 - 21 Activity of two benzofuran-imidazoles, IM/B/4-62 and IM/B/4-66, against experimental infections with Candida albicans and Trichophyton mentagrophytes; Dubini F et al.; The therapeutic activity of two new benzofuran-imidazoles, IM/B/4-62 and IM/B/4-66, formulated as 1% cream, has been evaluated against Candida albicans and Trichophyton mentagrophytes by inducing experimental vaginal candidosis in female rats and dermatophytosis in female guinea pigs . Results of the treatment were compared with those obtained by the same therapeutic regimen carried out with bifonazole . IM/B/4-66 proved to possess superior antimycotic activity to that of IM/B/4-62 and similar to that of bifonazole in both infections . Nmaley vaginal candidosis was cured in all the treated in animals at 6 days post-inoculation and skin lesions were healed in 9 of 10 animals at 15 days after infection, with negative cultures from all the infected sites. Adv Perit Dial, 1992, 8, 419 - 22 Peritonitis in children undergoing chronic peritoneal dialysis (CPD): data from the Italian Registry of Pediatric CPD; Verrina E et al.; During the period 1986-1990, 119 patients were enrolled in the Italian Registry of Pediatric CPD . CAPD was largely predominant in the first 3 years, while CCPD accounted for 48% of dialysis months in the period 1989-1990 . The connect-disconnect system was a Y set for all patients during the whole observation period . The incidence of peritonitis decreased from 1 episode: 10.9 patient-months in 1986 to 1:19.8 in 1988, and then passed to 1:16.2 in 1990 . A comparison of the incidence of peritonitis between CAPD and CCPD, referring to the 1989-1990 period, showed no significant difference . The percentage of positive peritoneal fluid cultures changed from 48% in 1986 to 73% in 1990 . Gram-positive bacteria, primarily Staphylococcus aureus and Staphylococcus epidermidis, accounted for most of the isolated organisms . Candida albicans was cultured in 3 cases both in 1986 and 1987 . Exit site infection was the predominant (82%) complication, followed by leakage and catheter cuff extrusion . The hospitalization rate for peritonitis resulted persistently high (61% of episodes) and the mean duration was 12.7 days . Of the 8 patients who were switched to hemodialysis, 4 had recurrent peritonitis and 1 Candida albicans peritonitis. Acta Derm Venereol, 1992, 72(3), 187 - 92 Pityrosporum ovale and atopic dermatitis in children and young adults; Broberg A et al.; Children aged 0-21 years, 60 children with atopic dermatitis (AD), 40 children with rhinoconjunctivitis and or asthma (RA) and 40 children with no atopic history (HC) were studied to evaluate the relationship between skin colonisation with Pityrosporum ovale and the occurrence of specific IgE antibodies to P . ovale . The following studies were done: culture for P . ovale, measurement of IgE antibodies to P . ovale (skin prick test, RAST), Candida albicans, and Cladosporium herbarum (RAST) and IgG antibodies to P . ovale . P . ovale could be cultured with about the same frequency in children and young adults with AD and age-matched children with or without other atopic manifestations . In spite of similar colonisation, IgE antibodies against P . ovale occur only in atopy and more frequently in children with AD than in those with other types of atopic disease. Acta Derm Venereol, 1992, 72(3), 180 - 1 The skin as the possible reservoir for Candida albicans in the oculocutaneous candidiasis of heroin addicts; Elbaze P et al.; We describe 2 patients who injected themselves with the same brown heroin a few days before hospitalization . The first patient presented with characteristic oculo-cutaneous candidiasis . Blood samples remained sterile during the so-called 'septicemic syndrome' which represents the first phase of this syndrome and were positive for Candida albicans only when cutaneous nodules developed . The second patient was hospitalized for a stomach perforation and had no cutaneous or ocular candida involvement . Both patients were unusually colonized by C . albicans on their skin (particularly on hairy zones) . These observations support the hypothesis that the skin may constitute the reservoir for C . albicans in oculo-cutaneous candidiasis. Acta Derm Venereol, 1992, 72(1), 1 - 3 Candida albicans grown in glucose-free media contains serum-independent chemotactic activity; Brasch J et al.; Infection of skin with Candida albicans is usually followed by infiltration of neutrophil granulocytes (PMN) . So far, chemotaxins for PMN have been isolated from C . albicans cultures grown in the presence of glucose . However, since glucose is not present in skin in vivo, a contribution of such factors to Candida-triggered cutaneous inflammation would appear unlikely . In order to clarify this question, chemotactic activity was measured in extracts from three different strains of C . albicans which were grown in five different peptone media free of carbohydrates and serum . In addition, four culture systems were supplemented with lipids normally present in human stratum corneum, including a triglyceride, cholesterol, and sphingomyelin . In all sugar-free grown cultures, serum-independent chemotactic activity was detected by use of the Boyden chamber technique . Since, as shown here in vitro, production of neutrophil chemotaxins by C . albicans is independent of glucose-feeding, a possible role of Candida-chemotaxins in the pathophysiology of cutaneous candidosis can no longer be excluded. J Med Vet Mycol, 1992, 30(1), 27 - 34 Transport of acidic amino acids in Candida albicans; Gupta P et al.; In Candida albicans ATCC 10261, two kinetically different amino acid transport systems with a high (S1) and a low (S2) affinity for aspartic acid (asp) and glutamic acid (glu) were identified . The S1 for the two acidic amino acids was characterized by low Kt values while Kt values of S2 were 30 to 40 times higher . Based on competitive studies of both systems, S1 was found to be specific and common to both asp and glu while S2 was relatively less specific . The S1 and S2 systems were also different in their sensitivity to respiratory inhibitors, mercurials and a K+ channel blocker . Both systems, however, showed maximum transport rates during the mid-exponential growth phase. Mol Microbiol, 1992 Jan, 6(2), 171 - 7 Isolation, characterization, and genetic analysis of monosomic, aneuploid mutants of Candida albicans; Barton RC et al.; A white, prototrophic Candida albicans strain, heterozygous for the ADE2 gene (ade2/ADE2), was treated with the antimitotic agent methyl benzimidazole carbamate, and yielded red, adenine-requiring colonies at a rate of 4 x 10(-3), an order of magnitude higher than the spontaneous rate of Ade- colony formation . These red Ade- colonies were small, growing at approximately half the rate of the parent strain, and gave rise to large red colonies spontaneously . When the chromosomes of the small red colonies were separated by pulsed-field gel electrophoresis, the band hybridizing with the ADE2 gene was diminished in staining intensity by half relative to the parent and large red-colony strains . Restriction fragment-length polymorphism analysis and auxotrophic mutant spectra after mutagenesis suggested that the small red Ade- strains were monosomic aneuploids lacking one of a pair of chromosome homologues, while the large red strains had regained a homologue, presumably via a second non-disjunction event . Parasexual genetic analysis of two of the auxotrophs isolated from a putative aneuploid suggested that both mutations were linked to the ADE2 gene . These experiments suggest that targeted chromosome loss and monosomic, aneuploid strains have the potential to extend the scope of genetic analysis in this diploid, asexual organism. Braz J Med Biol Res, 1992, 25(10), 1015 - 24 Phagocytosis of enteropathogenic Escherichia coli and Candida albicans by lectin-like receptors; Pacheco-Soares C et al.; 1 . Ingestion of enteropathogenic Escherichia coli or Candida albicans by thioglycollate-elicited macrophages and polymorphonuclear leukocytes was investigated in vitro, 2 . Goat antiserum against mannose receptors caused about 50% inhibition of E . coli phagocytosis and about 90% inhibition of C . albicans phagocytosis . 3 . E . coli and C . albicans uptake was inhibited by about 60% and 98%, respectively, by plating the macrophages onto substrates coated with poly-L-lysine-mannan . Further addition of 50 mM mannose to the medium significantly increased the inhibition of phagocytosis of E . coli by macrophages from 60.7 +/- 1.5 to 79.8 +/- 13.1 and by polymorphonuclear cells from 58.9 +/- 3.7 to 88.7 +/- 4.9 . 4 . Preincubation of phagocytic cells with antiserum against substance A of human erythrocytes reduced E . coli ingestion by 95%, but this inhibition was not observed when the antiserum was incubated with N-acetylgalactosamine (50 mM) before being added to the phagocytes . The phagocytosis of C . albicans was not inhibited by anti-substance A antiserum . 5 . The phagocytosis of E . coli was inhibited by about 25% by the addition of 7.8 micrograms/ml soluble mannan to the medium, and by about 50% by the addition of 50 mMN-acetylgalactosamine; when both substances were added to the medium, an additive inhibition of about 75% was observed . 6 . These results indicate that mannose receptors on the surface of phagocytic cells mediate E . coli or Candida albicans uptake and that the binding of bacteria to N-acetylgalactosamine residues from the membrane of phagocytes is also involved in the phagocytosis of E . coli. Braz J Med Biol Res, 1992, 25(2), 167 - 74 Evidence for the participation of proteinases released by Candida albicans in the early killing of peritoneal macrophages in vitro; de-Andrade GM et al.; 1 . We have investigated the possibility that proteinases released by Candida albicans participate in the early killing of three types of mice peritoneal macrophage (resident, thioglycollate-elicited, or Con A-activated) in vitro . 2 . Phagocytic assays were performed by incubation of macrophages and C . albicans together at a 1:10 ratio for 30 min at 37 degrees C in RPMI medium buffered to pH 7.0 with 12 mM Hepes without serum . With no albumin added to the medium, the macrophages were 85% to 100% damaged and unviable, to a greater extent than expected from the proportion of phagocytic cells containing germ tubes . When 10 mg/ml of albumin was added to the medium, however, 90% of the macrophages remained viable for the 2 hours of the phagocytic assay, suggesting that albumin may have acted as a substrate for or inhibitor of proteinases released by C . albicans, thereby protecting the macrophage from the proteolytic action of the proteinases . 3 . The phagocytosis of IgG-coated erythrocytes was reduced to 43% when IgG was preincubated with the supernatant from C . albicans cultures, but the addition of 10 mg/ml albumin or of 5 micrograms/ml pepstatin (an inhibitor of C . albicans acid proteinases) to the same supernatants prevented the effect on phagocytosis of IgG-coated erythrocytes . 4 . These results suggest that proteinases released from C . albicans are involved in the early killing of macrophages. Immunopharmacol Immunotoxicol, 1992, 14(4), 813 - 40 Effect of zinc on immune functions and host resistance against infection and tumor challenge; Singh KP et al.; The effect of zinc treatment on immune function and resistance against infection and tumor challenge was studied in mice . Swiss albino mice were treated with zinc acetate (3 mg/kg body weight) in one or two intraperitoneal injections . Various immune function assays were performed in treated animals . Zinc treatment to normal animals caused potentiation of T-lymphocyte and macrophage functions . Zinc treatment was also found to increase host resistance against Candida albicans and Semliki Forest virus infections . Increased resistance against endotoxin shock and Ehrlich's ascites tumor challenge was also observed in zinc treated animals . It can be stated from this study that zinc treatment potentiates the cell mediated immunity and host resistance against infection and tumor challenge. Eur J Gynaecol Oncol, 1992, 13(5), 398 - 402 Cytologic evidence of the association of different infective lesions with dysplastic changes in the uterine cervix; Chakrabarti RN et al.; Cervical smears from 4055 women were examined and classified as per WHO criteria . 873 (21.53%) smears revealed dysplastic changes . The dysplastic smears were further examined cytologically for the presence of Chlamydia trachomatis, Herpes simplex virus type-2, Human papilloma virus, Trichomonas vaginalis and Candida albicans . Chlamydia was found to be the commonest micro-organism associated with cervical dysplasia followed by Herpes simplex virus type-2 and Human papilloma virus . The association of Trichomonas and Candida with cervical dysplasia was found to be insignificant . Cervical dysplasia associated with Herpes simplex virus type-2 commonly occurred in the early reproductive life . The data observed in this study provide useful baseline information for detecting the subjects harbouring the infective microbes in the cervical epithelium. Br J Neurosurg, 1992, 6(5), 501 - 4 Ventriculitis and hydrocephalus caused by Candida albicans successfully treated by antimycotic therapy and cerebrospinal fluid shunting; Jamjoom A et al.; A unique case of Candida albicans ventriculitis and hydrocephalus in the absence of any evidence of systemic candidiasis or immunosuppression is reported . Initial treatment with CSF shunting and intravenous antimycotic therapy appeared to have eradicated the infection . Recurrence occurred 5 months after discharge and this was treated by intravenous and intrathecal antimycotic therapy in addition to removal of the shunt system, external ventricular drainage and then replacement of the shunt . A concomitant pyogenic brain abscess responded to burrhole aspiration and antibiotics . The role of mannan antigen monitoring is discussed. J Med Vet Mycol, 1992, 30(3), 233 - 43 A basis for