Respuesta de la regeneración natural en manglares del Golfo de Urabá (Colombia) a la variabilidad ambiental y climática intra-anual / Natural regeneration response in mangroves of the Gulf of Urabá (Colombia) to the environmental and intra-annual climate variability

The natural regeneration process allows the mangrove forests remain over time. Both, biological and physical factors can affect the establishment and early stages along the development of trees. This study examined the response of natural regeneration of mangroves in the Turbo River delta and El Uno bay (Urabá Gulf, Colombia) to intra-annual environmental variability. We quantified mortality, survival and recruitment of seedlings of three mangrove species, seasonally during one year, in 72 semi-perma-nent sub-plots of 1m². In the sub-plots, the total height and the diameter at the base of the stem of all mangrove seedlings with basal diameter less than 2.5cm were measured. Damage by herbivores was also recorded to each seedling. While Laguncularia racemosa recorded the highest rates of mortality, Rhizophora mangle showed the highest survival rate during the study period, although Avicennia germinans dominated the natural regeneration. Through a Redundancy Analysis these processes were associated to environmental variables such as: Direct Site Factor-DSF (sunlight), sediments input rate, herbivory, distances from mangroves to the river, to inner lakes, and to the coastline. These variables explained 43% of the natural regeneration variation; sedimentation rate was the most important variable, while light was very representative for the R. mangle survival. Based on historical records of precipitation, Turbo River flow rate and associated sediment loads, it was established that during the highest precipitation peak, the survival of all species decreases and during the dry season, when the conditions of flooding and sediments input were lower, it was improved. The results indicated that the sediments input rates and sunlight play an important role in the survival of natural regeneration of evaluated mangrove species.

En los bosques de mangle, tanto factores biológicos como físicos, afectan el establecimiento y los estados tempranos de desarrollo de los árboles y determinan la distribución espacial de las especies. Se evaluó la respuesta de la regeneración natural de los manglares del delta del río Turbo y la bahía El Uno a la variabilidad ambiental y climática intra-anual. Se cuantificaron la mortalidad, la sobrevivencia y el reclutamiento de las plántulas de tres especies, estacionalmente durante un año. Avicennia germinans dominó la regeneración natural, Rhizophora mangle presentó la mayor la supervivencia y Laguncularia racemosa la mayor mortalidad. Estos procesos se asociaron principalmente con el aporte de sedimentos aluviales, la disponibilidad de luz, la herbivoría, la distancia al río, a las lagunas internas y a la línea de costa, las cuales explicaron el 43% de la variación en la regeneración. La sedimentación fue la variable más importante para el reclutamiento de A. germinans, mientras la luz fue muy representativa para la supervivencia de R. mangle. Con base en registros históricos de precipitación, caudales y carga de sedimentos, se estableció que en la época con mayor precipitación se presenta un descenso en la supervivencia, y en la época seca se favorece el balance entre el reclutamiento y la mortalidad. Los resultados indicaron que la precipitación, el aporte de sedimentos y la luz desempeñan un papel importante en el proceso de la regeneración de las especies evaluadas.

El modelo de promoción de la salud de Nola Pender. Una reflexión en torno a su comprensión / The model of health promotion proposed by Nola Pender. A reflection on your understanding

La comprensión de las teorías y modelos de enfermería llevan consigo un amplio recorrido de discusión que contribuye al crecimiento de la disciplina. El Modelo de Promoción de la Salud propuesto por Nola Pender, es ampliamente utilizado por los profesionales de enfermería, ya que permite comprender comportamientos huma - nos relacionados con la salud, y a su vez, orienta hacia la generación de conductas saludables. El objetivo del presente trabajo fue realizar un análisis de los artículos originales publicados en torno a este modelo, durante el período 2000­2010, identificando los aspectos más relevantes expresados en dichas publicaciones, así como las formas en que éste es interpretado y utilizado en la práctica. Las investigaciones realizadas a partir de este modelo, en el periodo mencionado, predominan en Brasil, Estados Unidos de América y México. Los grupos de personas en las que más se hacen, son adolescentes y adultos, las temáticas más mencionadas son: Actividad física, estilos de vida saludable, enfermedades crónicas y obesidad, la gran mayoría de los investigadores, utiliza la totalidad de conceptos expresados en el modelo para la interpretación del fenómeno estudiado. Los profesionales que más investigan en torno a este modelo, son de los campos de enfermería y sociología. Se ha notado un incremento de las investigaciones alrededor del Modelo de Promoción de la Salud en la última década, reflejo del interés de estos expertos por comprender las conductas promotoras de la salud, así como de las motivaciones que llevan a realizarlas.

Comprehension of theories and Nursing Models comprise a wide range of discussions contributing to the growth of discipline. The model of health promotion proposed by Nola Pender is widely used by Nursing professionals; as it leads to the understanding of human behavior related to health; it also leads to the development of healthy behavior. The aim of this work is to perform an analysis of the original articles published regarding this model, carried out between 2000 and 2010 in America identifying the most relevant issues stated under such publications, and the ways it is interpreted in real practice. Research performed from this model in the above stated period of time, is mostly used in Brazil, the United States and Mexico. The groups of people widely involved are youngsters, adults and elders, most used topics are: physical activity, healthy life styles, chronicle diseases and the application of the model instruments, most of the researches use the whole of the concepts expressed in the model for the interpretation of the surveyed phenomenon. Nurses and Sociologists are the professionals performing most of the research of this model. An increase of HMP (Health Model Promotion) research has been detected in the last decade, evidencing the interest of these experts to understand the Promotional Health Behaviors, as well as the motivational aspects that lead them to perform them.

Reformas sanitarias e indicadores de atención / Sanitary reforms and AIDS health care indicators: comparison between two specialized remission services

La reforma colombiana del Sistema General de Seguridad Social en Salud (SGSSS) lo transformó en un modelo basado en el mercado regulado de los seguros en salud, que ha generado cambios profundos en la oferta de servicios y en el perfil epidemiológico. La política sanitaria se expresa de manera especial en los programas de control del sida y se refleja en sus indicadores. Objetivo: describir la atención médica en dos centros de referencia para el control del VIH/sida que actuaron antes (servicio A) y después (servicioB) de la reforma del SGSSS, como indicadores de política sanitaria. Materiales y métodos: estudio retrospectivo sobre la totalidad de los 1.252 casos de infección por VIH registrados por ambos serviciosespecializados, entre 1986 y 2002. Resultados: para cada serviciose obtuvieron indicadores de referencia, diagnóstico,tratamiento, riesgo de sida, supervivencia y letalidad. Conclusiones:se identificaron condiciones desfavorables del servicio B quesugieren un deterioro en la efectividad de los programas de controldel VIH/sida en la continuidad de las intervenciones y en el funcionamientodel sistema asistencial de referencia en la región. Estosfactores podrían relacionarse con barreras administrativas impuestaspor los requisitos del aseguramiento y explicar la gravedad delos casos al momento de su remisión. La terapia antirretroviral específicase mostró efectiva para reducir la letalidad y mejorar lasupervivencia; sin embargo, su uso fue irregular y tardío y no logróreducir la incidencia de sida entre los infectados. El estudio sugierela aparición de fallos en el modelo sanitario, que afectan la calidady eficiencia del control del VIH/sida.Palabras claveInfección por VIH, síndrome de inmunodeficiencia adquirida, evaluaciónde programas, reforma a la atención en salud, Colombia, políticas en...

Mortalidad evitable por comuna. Medellín 1994-1998 / Avoidable mortality according to district divisions in Medellin

Se presenta la distribución de la mortalidad evitable por comuna para la ciudad de Medellín de 1994 a 1998. Las tasas medianas generales más altas se presentaron en los grupos de muertes violentas, diagnóstico o tratamiento médico precoz e infecciones de las vías respiratorias (224,01, 16,99 y 16,45 por cada cien mil habitantes, respectivamente). El primer grupo presentó las tasas más altas en todas las comunas, entre las que se destacan Santa Cruz, Castilla, La Candelaria y Guayabal, con indicadores por encima del tercer cuartil general (tasa de 270,38 por cien mil habitantes). El segundo grupo predominó en las comunas de La Candelaria, Laureles-Estadio, La América y Buenos Aires (tasas medianas de 40,57, 30,15, 25,76 y 23,24, respectivamente, por cada cien mil habitantes). En el tercer grupo, la comuna de La Candelaria presentó la mayor tasa mediana general de mortalidad evitable, que fue seis veces la de la comuna del 12 de Octubre. La relación observada al considerar la tasa mediana general de las 16 comunas en cada grupo con el grupo F, el de evitabilidad por muertes violentas, fue de 1 a 30 en el grupo A, de 1 a 13 en el grupo B, de 1 a 52 en el grupo C, de 1 a 14 en el grupo D, de 1 a 19 en el grupo E y de 1 a 36 en el grupo G

A developmental transition in definitive erythropoiesis: erythropoietin expression is sequentially regulated by retinoic acid receptors and HNF4.

The cytokine erythropoietin (Epo) promotes erythropoietic progenitor cell proliferation and is required for erythropoietic differentiation. We have found that the Epo gene is a direct transcriptional target gene of retinoic acid signaling during early erythropoiesis (prior to embryonic day E12.5) in the fetal liver. Mouse embryos lacking the retinoic acid receptor gene RXR alpha have a morphological and histological phenotype that is comparable with embryos in which the Epo gene itself has been mutated, and flow cytometric analysis indicates that RXR alpha-deficient embryos are deficient in erythroid differentiation. Epo mRNA levels are reduced substantially in the fetal livers of RXR alpha(-/-) embryos at E10.25 and E11.25, and genetic analysis shows that the RXR alpha and Epo genes are coupled in the same pathway. We furthermore show that the Epo gene is retinoic acid inducible in embryos, and that the Epo gene enhancer contains a DR2 sequence that represents a retinoic acid receptor-binding site and a retinoic acid receptor transcriptional response element. However, unlike Epo-deficient embryos that die from anemia, the erythropoietic deficiency in RXR alpha(-/-) embryos is transient; Epo mRNA is expressed at normal levels by E12.5, and erythropoiesis and liver morphology are normal by E14.5. We show that HNF4, like RXR alpha a member of the nuclear receptor family, is abundantly expressed in fetal liver hepatocytes, and is competitive with retinoic acid receptors for occupancy of the Epo gene enhancer DR2 element. We propose that Epo expression is regulated during the E9.5--E11.5 phase of fetal liver erythropoiesis by RXR alpha and retinoic acid, and that expression then becomes dominated by HNF4 activity from E11.5 onward. This transition may be responsible for switching regulation of Epo expression from retinoic acid control to hypoxic control, as is found throughout the remainder of life.

A new regulatory region of the IL-2 locus that confers position-independent transgene expression.

Although the promoter/enhancer of the IL-2 gene mediates inducible reporter gene expression in vitro, it cannot drive consistent expression in transgenic mice. The location and existence of any regulatory elements that could open the IL-2 locus in vivo have remained unknown, preventing analysis of IL-2 regulation in developmental contexts. In this study, we report the identification of such a regulatory region, marked by novel DNase-hypersensitive sites upstream of the murine IL-2 promoter in unstimulated and stimulated T cells. Inclusion of most of these sites in an 8.4-kb IL-2 promoter green fluorescent protein transgene gives locus control region-like activity. Expression is efficient, tissue specific, and position independent. This transgene is expressed not only in peripheral T cells, but also in immature thymocytes and thymocytes undergoing positive selection, in agreement with endogenous IL-2 expression. In contrast, a 2-kb promoter green fluorescent protein transgene, lacking the new hypersensitive sites, is expressed in only a few founder lines, and expression is dysregulated in CD8(+) cells. Thus, the 6.4 kb of additional upstream IL-2 sequence contains regulatory elements that provide integration site independence and differential regulation of transgene expression in CD8 vs CD4 cells.

Las proteínas e en la selección positiva y el desarrollo de los timocitos / E-box proteins in positive selection and lineage commitment of thymocytes

En el proceso de selección positiva, los timocitos doble positivos (DP) se diferencian en células maduras CD8 o CD4, según la especificidad de su receptor para el antígeno (TCR) por moléculas del complejo mayor de histocompatibilidad de clase I, o clase II, respectivamente. De esta forma se conjuga la especificidad del TCR con la diferenciación hacia el linaje apropiado. El destino de los timocitos es controlado por la intensidad de la señal aporta al complejo TCR/CD3 la tirosincinasa Lck asociada al correceptor correspondiente. No obstante, las señales que transmiten y controlan estas decisiones no han sido bien caracterizadas. En esta revisión presentamos diferentes evidencias experimentales que sugieren que miembros de la famila helix - loop - helix (bHLH) de factores de transcripción, las proteinas E - box, juegan un importante papel en algunos aspectos del proceso de selección positiva (AU)

Lck activity controls CD4/CD8 T cell lineage commitment.

Thymocytes carrying MHC class I-restricted TCRs differentiate into CD8 T cells, while those recognizing MHC class II become CD4 T cells. The mechanisms underlying how MHC class recognition, coreceptor expression, and effector function are coordinated are not well understood. Since the tyrosine kinase Lck binds with more affinity to CD4 than CD8, it has been proposed as a candidate to mediate this process. By using transgenic mice with altered Lck activity, we show that thymocytes carrying a class II-restricted TCR develop into functional CD8 T cells when Lck activity is reduced. Conversely, thymocytes carrying a class I-restricted TCR develop into functional CD4 T cells when Lck activity is increased. These results directly show that quantitative differences in the Lck signal control the CD4/CD8 lineage decision.

The lymphopenia mutation of the BB rat causes inappropriate apoptosis of mature thymocytes.

BB rats develop autoimmune diabetes mellitus at a high frequency. A key factor in the development of the disease is an autosomal recessive mutation determining peripheral T cell lymphocytopenia. Previous studies have suggested that the lymphopenia could be caused by increased cell death. Here we demonstrate that the lyp mutation dramatically reduces the in vitro lifespan of the TCRhi single-positive thymocytes and peripheral T cells, without abolishing their capacity to proliferate. The reduced lifespan is due to an increased rate of apoptosis, and is detected in single-positive thymocytes displaying characteristics of cells which have undergone positive selection. The cell death defect does not affect the in vitro lifespan of peripheral B cells. Interestingly, stimulation can rescue peripheral lyp/lyp T cells from immediate cell death. We propose that the lymphopenia mutation prevents the accumulation of a normal T cell pool, including regulatory subsets, without preventing the activation and proliferation of reactive T cells, thereby creating conditions appropriate for the development of uncontrolled autoimmune responses.

Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage.

Ets family transcription factors control the expression of a large number of genes in hematopoietic cells. Here we show strikingly precise differential expression of a subset of these genes marking critical, early stages of mouse lymphocyte cell-type specification. Initially, the Ets family member factor Erg was identified during an arrayed cDNA library screen for genes encoding transcription factors expressed specifically during T cell lineage commitment. Multiparameter fluorescence-activated cell sorting for over a dozen cell surface markers was used to isolate 18 distinct primary-cell populations representing discrete T cell and B cell developmental stages, pluripotent lymphoid precursors, immature NK-like cells and myeloid hematopoietic cells. These populations were monitored for mRNA expression of the Erg, Ets-1, Ets-2, Fli-1, Tel, Elf-1, GABPalpha, PU.1 and Spi-B genes. The earliest stages in T cell differentiation show particularly dynamic Ets family gene regulation, with sharp transitions in expression correlating with specification and commitment events. Ets, Spi-B and PU.1 are expressed in these stages but not by later T-lineage cells. Erg is induced during T-lineage specification and then silenced permanently, after commitment, at the beta-selection checkpoint. Spi-B is transiently upregulated during commitment and then silenced at the same stage as Erg. T-lineage commitment itself is marked by repression of PU.1, a factor that regulates B-cell and myeloid genes. These results show that the set of Ets factors mobilized during T-lineage specification and commitment is different from the set that maintains T cell gene expression during thymocyte repertoire selection and in all classes of mature T cells.

Chromatin remodeling of the interleukin-2 gene: distinct alterations in the proximal versus distal enhancer regions.

Known transcription factor-DNA interactions in the minimal enhancer of the murine interleukin-2 gene (IL-2) do not easily explain the T cell specificity of IL-2 regulation. To seek additional determinants of cell type specificity, in vivo methodologies were employed to examine chromatin structure 5' and 3' of the 300 bp IL-2 proximal promoter/enhancer region. Restriction enzyme accessibility revealed that until stimulation the IL-2 proximal promoter/enhancer exists in a closed conformation in resting T and non-T cells alike. Within this promoter region, DMS and DNase I genomic footprinting also showed no tissue-specific differences prior to stimulation. However, DNase I footprinting of the distal -600 to -300 bp region revealed multiple tissue-specific and stimulation-independent DNase I hypersensitive sites. Gel shift assays detected T cell-specific complexes binding within this region, which include TCF/LEF or HMG family and probable Oct family components. Upon stimulation, new DNase I hypersensitive sites appeared in both the proximal and distal enhancer regions, implying that there may be a functional interaction between these two domains. These studies indicate that a region outside the established IL-2 minimal enhancer may serve as a stable nucleation site for tissue-specific factors and as a potential initiation site for activation-dependent chromatin remodeling.

Length of postpartum anestrus in goats in subtropical Mexico: effect of season of parturition and duration of nursing.

The aim of this study was to determine whether season of birth and length of nursing affected the duration of postpartum anestrus in Creole female goats maintained on a constant plane of nutrition in subtropical Mexico. Three experiments were conducted in the Laguna region in the State of Coahuila, Mexico (26 degrees N). In the first experiment, 34 goats gave birth in January; in the second, 31 females gave birth in May; and in the third, 22 goats kidded in October. At parturition, females were allocated to 1 of 3 groups based on body weight and date of parturition: kids were weaned at 2, 30 or 90 d according to their group. After weaning, females were milked manually once a day until the end of the study. All animals were kept in a shed and were fed alfalfa ad libitum and given 200 g of concentrate daily. Starting 1 wk after parturition, estrous behavior was detected twice daily using an apron-bearing male, and blood samples were obtained twice weekly to determine ovarian activity from the plasma progesterone levels. A strong effect of month of parturition was found on the duration of postpartum anestrus (P < 0.0001), which was longer in females kidding in January (about 200 d) than in those kidding in May (about 100 d) or October (about 50 d). A tendency for an interaction between season of parturition and length of nursing was observed in the length of anovulation (P < 0.07): for parturition in October, anestrus was longer when kids were weaned after 90 d than after 2 or 30 d (P < 0.01). Season of parturition also affected dates of reinitiation of ovulatory and estrous activity (P < 0.001). Proportions of normal, short and long cycles and of associations between estrous and ovulations were not influenced by season of parturition or the age of weaning. These data demonstrate that in subtropical latitudes, season of parturition can dramatically influence the duration of postpartum anestrus independently of the availability of food.

[Preferential habits of consumers of common bean (Phaseolus vulgaris L.) in Mexico]. / Hábitos preferenciales de los consumidores de frijol común (Phaseolus vulgaris L.) en México.

A detailed knowledge of the consumer's preferences for the different classes of common bean is useful to define objectives in bean breeding and quality projects in a given region or country and it is also a valuable tool to design marketing strategies. The present work consisted on the application of a survey to 1514 common bean consumers in 14 states of Mexico. To facilitate the interpretation of the results the country was divided in four regions: North East, North West, Center and South. In the North West region, 98% of the surveyed individuals eat the "Azufrado" types (sulphur yellow); in the North East, 70% of the consumers prefer "pinto" (beige with brown mottles) and "Bayo" (cream) types; in the South, 90% of the consumers prefer the "Black" type; and in the Center of the country, all commercial classes are consumed. Within a commercial class, specific characteristics are demanded. For instance, in the black type, small and opaque seeds are preferred while in the "Flor de mayo" (Beige with pink mottles) type medium to large seeds having bright seed coat are preferred. The main characteristics utilized by consumers to select a given bean type are cooking time and flavor. It was observed that preferential classes are well established among the consumers since 70% responded that they would not change the preferred class even if the alternative class was sold to a lower price. Consumers do not soak the beans, because it changes the flavor and the aspect of the cooked beans and they do not add salt at the beginning of the cooking process due to the same reason. Organoleptic studies conducted in the laboratory confirmed that soaking of beans or addition of salts in the soaking water or at the beginning of the cooking process negatively affected acceptability of cooked beans by panelists. In this paper aspects related to ways of processing and consuming common beans as well as marketing aspects are discussed.

Waste Corn as a Point Source of Inoculum for Aspergillus flavus in the Corn Agroecosystem.

Sporulation of Aspergillus flavus was detected on kernels in deposits of waste corn close to corn storage cribs and bins at 18 locations throughout Iowa in 1991 and 1992. A. flavus was detected in spore traps located 3 m from the deposits and was isolated from nitidulid beetles within the deposits or in insect traps within 3 m of the deposits. A. flavus also was isolated from asymptomatic corn kernels in the deposits and from soil beneath the deposits. Linear dispersal gradients of airborne conidia of A. flavus, sampled at distances of 2, 6, 10, and 14 m from waste corn deposits into adjacent cornfields, were detected at three sampling times between 28 July and 1 September 1992 at Cedar Rapids and Williamsburg, Iowa. Linear dispersal gradients from the deposits also were detected for A. flavus-infested nitidulid beetle species Carpophilus lugubris and Glischrochilus quadrisignatus. The incidence of A. flavus infection on corn leaves, silks, and kernels in the fields adjacent to the deposits were correlated to numbers of airborne conidia at each sampling time at both locations. In a field experiment in Ames in which waste corn was placed in the center of individual corn plots, linear dispersal of conidia of A. flavus and plant infection gradients similar to those found from natural deposits were detected at distances of 1.7 to 8.5 m from the deposits at four sampling times from 6 August to 26 September 1992. Few airborne conidia of A. flavus were detected, and no infection of leaves, silks, and kernels by A. flavus occurred in the corresponding noninfested control plots. This study showed that deposits of waste corn infested with A. flavus found in the vicinity of corn storage cribs and bins are point sources of inoculum for A. flavus in the corn agroecosystem.

Cambios craneofaciales y dentoalveolares después de la extracción de los primeros molares permanentes / Craniofacial and dentoalveolar changes after the extraction of first permanent molars –Preliminary Report

Los individuos seleccionados para este estudio (actualmente 7 pacientes) debían cumplir con las siguientes características: edad entre 5 y 10 años, relación molar clase 1, perfil esquelético recto, presencia radiológica de segundo y tercer molares permanentes, ningún tipo de agenesia dental y primeros molares permanentes cariados. Para evaluar los cambios craneofaciales y dentoalveolares se tomaron radiografías cefálica lateral y panorámica modelos de estudio e índice de Helkimo. Los resultados corresponden a los primeros cuatro años del estudio. Algunos de los hallazgos son: disminución en la altura facial anterior inferior medida desde ENA hasta Mn en 2 de los 6 pacientes evaluados, disminución en el índice de irregularidad después de la extracción de los primeros molares permanentes, con distalización en cuerpo de los premolares e inclinación mesial del segundo molar permanente. No se ha presentado alteración patológica en la función de la ATM ni ningún efecto adverso dental, esquelético o funcional con la extracción de los primeros molares permanentes...

Ethylene: receptors and action.

The characterisation and purification of the ethylene binding protein from developing cotyledons of Phaseolus vulgaris is described. Polyclonal antibodies to this protein recognise homologous proteins in peas, tomatoes and Arabidopsis. Direct binding assays and results from immunological studies indicate that more binding protein is present in abscission zones of Phaseolus than in petioles; ethylene treatment increases binding site abundance in abscission zones. Binding sites for ethylene in peas. Arabidopsis and rice are described indicating that there exist two classes differing only in their rate constants of association and dissociation. Arabidopsis mutants wholly insensitive to ethylene may be receptor deficient and their possible use in receptor studies is assessed. It is proposed that those binding sites with high rate constants of association are functional receptors. The sites with low rate constants of association may be receptors but may also represent receptor precursors or internalised receptors.

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.

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.