PARACOCCIDIOIDOMYCOSIS: CHALLENGES IN THE DEVELOPMENT OF A VACCINE AGAINST AN ENDEMIC MYCOSIS IN THE AMERICAS.

Paracoccidioidomycosis (PCM), caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P. brasiliensis and P. lutzii, based on phylogenetic differences; however, the pathogenesis and disease manifestations of both are indistinguishable at present. Approximately 1,853 (~51,2%) of 3,583 confirmed deaths in Brazil due to systemic mycoses from 1996-2006 were caused by PCM. Antifungal treatment is required for patients with PCM. The initial treatment lasts from two to six months and sulfa derivatives, amphotericin B, azoles and terbinafine are used in clinical practice; however, despite prolonged therapy, relapses are still a problem. An effective Th1-biased cellular immune response is essential to control the disease, which can be induced by exogenous antigens or modulated by prophylactic or therapeutic vaccines. Stimulation of B cells or passive transference of monoclonal antibodies are also important means that may be used to improve the efficacy of paracoccidioidomycosis treatment in the future. This review critically details major challenges facing the development of a vaccine to combat PCM.

Paracoccidioidoyycosis: challenges in the develpment of a vaccine against an eendemic mycosis in the americas / Paracoccidioidomicose: desafios no desenvolvimento de uma vacina contra micose endêmica nas Américas

SUMMARYParacoccidioidomycosis (PCM), caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P. brasiliensis and P. lutzii, based on phylogenetic differences; however, the pathogenesis and disease manifestations of both are indistinguishable at present. Approximately 1,853 (~51,2%) of 3,583 confirmed deaths in Brazil due to systemic mycoses from 1996-2006 were caused by PCM. Antifungal treatment is required for patients with PCM. The initial treatment lasts from two to six months and sulfa derivatives, amphotericin B, azoles and terbinafine are used in clinical practice; however, despite prolonged therapy, relapses are still a problem. An effective Th1-biased cellular immune response is essential to control the disease, which can be induced by exogenous antigens or modulated by prophylactic or therapeutic vaccines. Stimulation of B cells or passive transference of monoclonal antibodies are also important means that may be used to improve the efficacy of paracoccidioidomycosis treatment in the future. This review critically details major challenges facing the development of a vaccine to combat PCM.

RESUMOA paracoccidioidomicose (PCM), causada por Paracoccidioides spp, é importante micose endêmica na América Latina. Com base em diferenças filogenéticas, existem duas espécies reconhecidas de Paracoccidioides, P. brasiliensis e P. lutzii, no entanto, a patogênese e as manifestações clínicas de ambas são indistinguíveis atualmente. Aproximadamente 1853 (~51,2%) de 3583 mortes confirmadas, atribuídas a micoses sistêmicas de 1996-2006, no Brasil foram causadas por PCM. Tratamento antifúngico é necessário para pacientes com PCM. O tratamento inicial dura de dois a seis meses e derivados de sulfa, anfotericina B, azóis e terbinafina são utilizados na prática clínica; no entanto, apesar da terapêutica prolongada, as recaídas ainda são um problema. Uma resposta imune celular eficaz, tendendo a Th1, é essencial para controlar a doença que pode ser induzida por antígenos exógenos, ou moduladas por vacinas profiláticas ou terapêuticas. A estimulação de células B ou a transferência passiva de anticorpos monoclonais também são meios importantes que podem ser utilizados para melhorar a eficácia do tratamento da paracoccidioidomicose no futuro. Esta revisão detalha criticamente os principais desafios que o desenvolvimento de uma vacina para combater a PCM enfrenta.

Human hand descriptions and gesture recognition for object manipulation.

This work focuses on obtaining realistic human hand models that are suitable for manipulation tasks. A 24 degrees of freedom (DoF) kinematic model of the human hand is defined. The model reasonably satisfies realism requirements in simulation and movement. To achieve realism, intra- and inter-finger constraints are obtained. The design of the hand model with 24 DoF is based upon a morphological, physiological and anatomical study of the human hand. The model is used to develop a gesture recognition procedure that uses principal components analysis (PCA) and discriminant functions. Two simplified hand descriptions (nine and six DoF) have been developed in accordance with the constraints obtained previously. The accuracy of the simplified models is almost 5% for the nine DoF hand description and 10% for the six DoF hand description. Finally, some criteria are defined by which to select the hand description best suited to the features of the manipulation task.

Colestasis neonatal y del lactante / Cholestasis in newborns and infants

La enfermedad hepática durante el primer año de vida se va a manifestar de manera fundamental como colestasis, independientemente de las distintas entidades etiológicas que la producen: infecciones víricas, bacterianas y por protozoos (toxoplasmosis), errores del metabolismo como tirosinemia, galactosemia e intolerancia a la fructosa, déficit de alfa-1-antitripsina, colangiopatías obstructivas, atresia de vías biliares extrahepáticas o lesiones hepáticas secundarias a trastornos sistémicos (fibrosis quística), aunque todas asociarán, en mayor o menor medida, necrosis hepatocitaria. Este es el motivo que dificulta un diagnóstico causal precoz, por otra parte muy importante en entidades como la atresia de vías biliares extrahepáticas (AVBE), cuya cirugía paliativa va a ser eficaz si se realiza en los dos primeros meses de vida. El interés de este trabajo, aprovechando la presentación de dos casos, radica en sistematizar los datos clínicos, bioquímicos, de imagen e histológicos que ayuden a establecer un diagnóstico etiológico precoz (AU)

[Orbital cellulitis in childhood. Medical-surgical treatment]. / Celulitis orbitaria en la infancia. Tratamiento médico-quirúrgico*

Orbital cellulitis is an uncommon complication resulting from a spectrum of disorders commonly found in pediatric practice. It usually occurs as a complication of infection of the paranasal sinuses, although it also can be caused by eyelid or dental juries, dental infection and external ocular infection. We studied the clinical, microbiological, and therapeutic features of 152 children diagnosed as periorbital cellulitis and 27 children with orbital cellulitis admitted to our hospital in a 16-year period from January 1983 to December 1998. Twenty-four percent of patients (43 cases) had positive cultures. Thirty children with septal or preseptal cellulitis developed neurological or ophthalmological complications. Intravenous or oral antibiotic administration was effective in 150 patients, but a significant proportion required surgery of the paranasal sinus or orbit (16%).

Use of the 27-kilodalton recombinant protein from Paracoccidioides brasiliensis in serodiagnosis of paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is one of the most important endemic mycoses in Latin America; it is usually diagnosed by observation and/or isolation of the etiologic agent, Paracoccidioides brasiliensis, as well as by a variety of immunological methods. Although the latter are effective, two circumstances, cross-reactions with other mycotic agents and antigen preparation that is marked by extreme variability among lots, hinder proper standardization of the procedures. To circumvent this lack of reproducibility, molecular biology tools were used to produce a recombinant 27-kDa-molecular-mass antigen from this fungus; a sizable quantity of this antigen was obtained through fermentation of Escherichia coli DH5alpha, which is capable of expressing the fungal protein. The latter was purified by the Prep-Cell System (Bio-Rad); the recovery rate of the pure protein was approximately 6%. A battery of 160 human serum samples, consisting of 64 specimens taken at the time of diagnosis from patients with PCM representing the various clinical forms plus 15 serum specimens each from patients with histoplasmosis and aspergillosis, 10 each from patients with cryptococcosis and tuberculosis, 6 from patients with coccidioidomycosis, and 40 from healthy subjects, were all tested by an indirect enzyme-linked immunosorbent assay with the purified 27-kDa recombinant protein. The latter was used at a concentration of 1.0 microgram/well; there were three serum dilutions (1:1,000, 1:2,000, and 1:4,000). The experiment was repeated at least twice. The average sensitivity for both experiments was 73.4%; in comparison with the healthy subjects, the specificity for PCM patients was 87.5% while for patients with other mycoses, it was 58.7%. Important cross-reactions with sera from patients with aspergillosis and histoplasmosis were detected. The positive predictive value of the test was 90.4%. These results indicate that it is possible to employ recombinant antigenic proteins for the immunologic diagnosis of PCM and, by so doing, achieve high coverage rates. Furthermore, antigen reproducibility can now be ensured, thus facilitating inter- and intralaboratory standardization.