Search PubMed⌕ Search

Biomedical subjects

A Restrepo

Publications and source records attributed to A Restrepo.

At least 91 records · Page 5Linked to original sources
PubMed1986

An evaluation of the enzyme-linked immunoabsorbent assay (ELISA) for quantitation of antibodies to Paracoccidioides brasiliensis.

The ELISA procedure was adapted for quantitation of antibodies against Paracoccidioides brasiliensis. Using a yeast cytoplasmic antigen and sera from patients with proven paracoccidioidomycosis, we found that 66% of sera reacted at titers greater than or equal to 1:128. Titers of this magnitude were obtained only for 4-5% of sera from healthy blood donors, tuberculosis patients and patients with other systemic mycoses. The exception was sera from patients with histoplasmosis (36% had titers greater than or equal to 1:128). Follow-up of 10 paracoccidioidomycosis patients during the course of therapy indicated a gradual decrease in antibody titers. Because of the technical advantages of the ELISA procedure in comparison with the standard complement fixation test, the ELISA test has potential utility for the quantitative determination of antibodies in patients with paracoccidioidomycosis.

Antibodies, Fungal↗
PubMed1986

Itraconazole therapy in lymphangitic and cutaneous sporotrichosis.

Itraconazole, a new orally absorbable azole derivative, was used for the treatment of 17 patients with cutaneous and lymphangitic sporotrichosis. The drug, administered at a dose of 100 mg/day, proved to be effective in all cases. Lesions disappeared and cultures became negative after 90 to 180 days of therapy. There were no major side effects. Posttherapy evaluations, done in 14 of 17 cases for an average of 115 days, revealed no relapses. Objective evaluation of the treatment by means of a scoring system indicated complete resolution of the pretherapy abnormalities at varying periods; thus, 35.3% (six of 17) of the patients had recovered by 90 days, 45.4% (five of 11) by 120 days, and 83.3% (five of six) by 150 days of therapy. Consequently, therapy with itraconazole is an adequate alternative to iodide treatment in sporotrichosis.

Adolescent↗
PubMed1985

Morphogenesis of the mycelium-to-yeast transformation in Paracoccidioides brasiliensis.

The sequential changes observed during the mycelium to yeast transformation in Paracoccidioides brasiliensis were studied microscopically. The mycelial elements produced terminal and intercalary swellings which, later on, became chlamydospore-like structures. These increased in size, acquired a double contour and, finally, gave rise to multiple budding cells. Transformation was asynchronous. During the observation period, multiple budding cells and chlamydospores remained attached to the parent mycelium.

Fungi↗
PubMed1985

Lack of antibody induction by Histolyn-CYL, a new skin-testing reagent for histoplasmosis.

Histolyn-CYL, a yeast phase skin-test reagent, was administered to 85 histoplasmin-sensitive subjects living in the United States and South America. In a multicenter study, sera were obtained at the time the skin tests were read and again 3 weeks later. In no instance did the skin test induce significant complement-fixing antibody changes or antibodies detected by immuno-diffusion.

Adult↗
PubMed1985

Study of current and new drugs in a murine model of acute paracoccidioidomycosis.

A new murine model of acute paracoccidioidomycosis, whose features include pulmonary infection with dissemination, was used to study the efficacy of currently available drugs and new agents which might be useful clinically. Two oral imidazole drugs, ketoconazole (KTZ) and Bay l 9139 (l9); two oral triazoles, Bay n 7133 (n7) and ICI 153,066 (ICI); and two polyenes, amphotericin B (AMB) and N-D-ornithyl-amphotericin B methyl ester, were studied. KTZ was superior to n7 and l9, particularly after a less lethal challenge. The polyenes could diminish dissemination, but had only modest effects on the pulmonary infection; AMB appeared slightly more effective. ICI was the most effective drug studied, approximately 5-10 times more potent than KTZ on a milligram/kg body weight basis; it had marked effects on both pulmonary and disseminated disease. These initial applications of the model to therapeutic evaluation suggest sufficient flexibility and utility, with information obtainable after relatively short experiments.

Amphotericin B↗
PubMed1985

Treatment of paracoccidioidomycosis with itraconazole in a murine model.

A new triazole, itraconazole, was studied as oral therapy of paracoccidioidomycosis in a murine model. The Paracoccidioides brasiliensis isolate, susceptible to itraconazole in vitro, was given by intranasal challenge, producing acute pulmonary and disseminated disease. Therapy was given twice daily over 4 weeks, and animals observed over 2 months. The infection was lethal for 70-80% of controls (untreated or polyethylene glycol diluent), whereas all treated animals, given 10-200 mg kg-1 day-1, survived. Itraconazole was ineffective in eradicating lung disease in survivors, though effective in treatment of disseminated sites. Since the highest doses did not give a better response than the lower doses, pharmacokinetic studies were performed. These showed irregular curves and small increases in peak serum concentrations and total area under the serum concentration-time curves, which were not proportional to the dose. This non-linearity appears to be best explained by poor absorption. Itraconazole, from these studies, appears to have promise for the therapy of human paracoccidioidomycosis but possibly with a different formulation.

Animals↗
PubMed1985

The ecology of Paracoccidioides brasiliensis: a puzzle still unsolved.

Some aspects pertaining to the ecology of the dimorphic fungus, Paracoccidioides brasiliensis, are reviewed. The available facts concerning the interactions among the only known host (man), the environment (limited to certain Latin-American countries) and the parasite (with an unknown habitat), are analysed. Efforts are made to detect clue circumstances which may lead to discovery of the fungus micro-niche. An analysis of P. brasiliensis mycelial form reveals that such a form has the required capabilities to be the natural infectious form. Its requirements for a moist environment in vitro as well as the high relative humidity predominating in the heart of the endemic areas point towards the possibility of an aquatic--or at least, an extremely humid--habitat for P. brasiliensis.

Environmental Microbiology↗
PubMed1985

A yeast-derived antigen from Paracoccidioides brasiliensis useful for serologic testing.

Antigens prepared from P. brasiliensis yeast cells subjected to ultrasonic treatment proved reliable in the serological diagnosis of paracoccidioidomycosis. Detection of antibodies was possible in over 90% from paracoccidioidomycosis patients in tests with agar gel immunodiffusion and counterimmunoelectrophoresis. Specificity was high and only histoplasmosis sera produced cross reactions, albeit at a lower frequency (10%). The new antigens compared favorably to the standard yeast culture filtrate antigen used in the past and they have the advantage of being reproducible. Proper control of proteolysis is required if activity is to be preserved.

Antibodies, Fungal↗
PubMed1984

Effect of temperature on the mycelium to yeast transformation of Paracoccidioides brasiliensis.

The influence of temperature on Paracoccidioides brasiliensis mycelium to yeast transformation was studied by sequential microscopic observations of slide cultures. When incubated at temperatures above 28 degrees C, the mycelial elements gradually produced round to oval chlamydospores and later on, exhibited multiple budding. A sizeable proportion of mycelial elements transformed at 34 degrees C; however, multiple budding was important only at 37 degrees C.

Fungi↗
PubMed1984

Toxic effect of products of oxidative metabolism on the yeast form of Paracoccidioides brasiliensis.

The effectiveness of toxic oxygen metabolites in killing the yeast form of Paracoccidioides brasiliensis (the form that occurs in host tissues) was studied with a fluorescence method in vitro. The two isolates studied were similar in susceptibility and H2O2 alone was lethal with an LD50 of 15-25 mM. The addition of halide (5 X 10(-4) M) augmented the lethality of H2O2 and in that setting H2O2 was c.90% lethal at 5 X 10(-5) M. Killing was most effective in the presence of peroxidase, when only 5 X 10(-6) M H2O2 (a concentration attainable in vivo by phagocytes) was required for a 95% kill. Kinetic studies revealed that toxic concentrations of H2O2 alone or of the H2O2-halide-peroxidase (PPH) system produced significant killing in 1 min; killing was maximal in 15 min. The PPH system was the more rapid in action. The dependence of the PPH killing system on H2O2 was demonstrated by an absence of killing in the presence of catalase. The susceptibility of P. brasiliensis to H2O2 and the PPH system appeared different in some respects from that noted for other dimorphic fungal pathogens. These studies suggest that toxic oxygen metabolites are important in host defence against P. brasiliensis.

Catalase↗
PubMed1984

Estrogens inhibit mycelium-to-yeast transformation in the fungus Paracoccidioides brasiliensis: implications for resistance of females to paracoccidioidomycosis.

Evidence that disease due to the thermally dimorphic fungus Paracoccidioides brasiliensis occurs post-puberty predominantly in males led us to hypothesize that hormonal factors critically affect its pathogenesis. We show here that estrogens inhibit mycelial- to yeast-form transformation of P. brasiliensis in vitro. Transformation of three isolates was inhibited to 71, 33, and 19% of the control values in the presence of 10(-10), 10(-8), and 10(-6) M 17 beta-estradiol, respectively. The synthetic estrogen diethylstilbestrol was active but less potent than estradiol, whereas testosterone, 17 alpha-estradiol, tamoxifen, and corticosterone were inactive. This function was specifically inhibited, since yeast-to-mycelium transformation, yeast growth, and yeast reproduction by budding were unaffected by 17 beta-estradiol. Of note is the fact that mycelium-to-yeast transformation occurs as the first step in vivo in the establishment of infection. The cytosol of the three isolates studied possesses a steroid-binding protein which has high affinity for 17 beta-estradiol. We believe that this binding protein represents a P. brasiliensis hormone receptor which can also recognize mammalian estrogens. We hypothesize that the ability of estrogen to decrease or delay mycelium-to-yeast transformation at the initial site of infection contributes to or is responsible for the marked resistance of females, and that the binder described is the molecular site of action.

Cytosol↗
PubMed1984

Chronic murine paracoccidioidomycosis: effect of ketoconazole on clearance of Paracoccidioides brasiliensis and immune response.

In a murine model of chronic pulmonary and disseminated paracoccidioidomycosis, ketoconazole (100 mg kg-1 in 0.3% agar) given by gavage twice daily for 1 or 2 months enabled all mice to clear disseminated Paracoccidioides brasiliensis from the spleen. Clearance of P. brasiliensis from the lungs was more difficult, and was achieved in 60% of the mice treated for 2 months. Sera from agar-treated control mice at days 77 and 103 post-infection demonstrated precipitating antibodies to P. brasiliensis antigens, but sera from ketoconazole-treated mice were precipitin-negative, indicating a favorable prognosis. Delayed hypersensitivity reactions to P. brasiliensis antigens in ketoconazole-treated mice were not significantly greater than in controls; consequently this test correlated less well with response than levels of serum antibody. This is the first use of this animal model of paracoccidioidomycosis to study the effect of antifungal drug protocols on the resolution of the disease. It also demonstrates the utility of this model in addressing clinically relevant questions about this disease and its treatment.

Animals↗
PubMed1984

Paracoccidioidomycosis in the immunosuppressed host: report of a case and review of the literature.

A case of reactivated paracoccidioidomycosis in an immunosuppressed host is described, the first association of this disease with renal transplantation. His presentation and clinical course was similar to the general experience with this mycosis. his response to ketoconazole was delayed when compared with that in non-immunosuppressed patients. Ketoconazole produced a dramatic resolution of all symptoms within 7 months. Serial determinations of paracoccidioides complement fixing antibodies showed falling titers, accurately reflecting his clinical status. Comparisons are made with other endemic mycoses in immunosuppressed patients. More cases of paracoccidioidomycosis in immunosuppressed patients can be expected to occur as immunosuppressive therapy becomes more common in areas endemic for Paracoccidioides brasiliensis, and with current trends in migration and travel.

Complement Fixation Tests↗
PubMed1984

Fungal endocarditis caused by Arnium leporinum following cardiac surgery.

A case of fungal endocarditis caused by the coprophilous ascomycete Arnium leporinum is reported in a 19-year-old male living in Colombia. The fungus was seen in tissue and recovered in pure culture from peripheral emboli, a mitral valve, pus from an osteolytic lesion, and kidney. The patient died 21 months after cardiac surgery. The range of A. leporinum in the Americas is expanded to include Colombia.

Adult↗
PubMed1984

Murine model of paracoccidioidomycosis. Production of fatal acute pulmonary or chronic pulmonary and disseminated disease: immunological and pathological observations.

A model of fatal acute pulmonary or chronic pulmonary and disseminated paracoccidioidomycosis was developed by intranasal challenge of young (3-4-week-old) mice with high doses (2.5-10 X 10(7) units) or low doses (0.1-1 X 10(7)) of yeast-phase Paracoccidioides brasiliensis. Fatal acute paracoccidioidomycosis was dose dependent; 10, 5, and 2.5 X 10(7) viable units of P. brasiliensis produced 100%, 66%, and 17% mortality, respectively, within 11 days. The pathologic picture was that of consolidation with a neutrophil infiltrate. Infection of adult (7-8-week-old) mice with even 10 X 10(7) units did not produce acute fatal paracoccidioidomycosis. The model of fatal acute paracoccidioidomycosis lends itself well to studies of therapeutic intervention. Increasing degrees of chronic pulmonary-disseminated paracoccidioidomycosis were produced by pulmonary infection of young mice with 0.1-1 X 10(7) viable units of P. brasiliensis. Although mice in all groups appeared healthy, pathology in lungs, liver, and spleen was evident at 7 and 10 weeks postinfection. Histopathologic observation revealed acinonodular granulomatous inflammation. At 12 weeks postinfection, there was evidence of less pathology, and of clearing of abscesses. In contrast to the pathology produced by 0.1 X 10(7) P. brasiliensis in young mice, no pathology evident on gross examination was produced by a similar dose in adult mice. Immunological evaluations of mice with chronic pulmonary-disseminated disease showed that spleen cells, but not lymph node cells, had significantly depressed blastogenic responses to concanavalin A (ConA) early after infection. However, at 12 weeks postinfection, when pathological examination indicated beginning resolution of infection, spleen cell responses to ConA were normal. The model of chronic disease is of interest for further immunological studies as well.

Acute Disease↗
PubMed1983

A comparison of mycelial filtrate - and yeast lysate - paracoccidioidin in patients with paracoccidioidomycosis.

A cytoplasmic antigen was obtained from P. brasiliensis yeast cells by water lysis and sonication, with the aim of detecting delayed hypersensitivity to the fungus. This antigen was studied in patients with paracoccidioidomycosis (active and inactive), tuberculosis and histoplasmosis as well as in normal individuals, and it was compared with a mycelial filtrate antigen employed in the past for the same purpose. The yeast paracoccidioidin proved superior to the mycelial preparation (62.0 vs 24.1%) in patients with active paracoccidioidomycosis; however, in inactive cases, both preparations gave similar results. The size of the reactions was also comparable for both products. In normal subjects and in patients with tuberculosis, skin reactivity was low (not over 10%) and within the expected range of the area. In contrast, patients with histoplasmosis proved highly reactive to both antigens. These results indicate that the newer paracoccidioidin has advantages over the mycelial product as it detects a higher proportion of reactors and as such, may be helpful in studies aimed at defining areas of endemicity in countries where paracoccidioidomycosis is present.

Adult↗