Glaucoma secundario a neurofibromatosis tipo-1 / Secondary glaucoma in neurofibromatosis type-1

Paciente de 59 años de edad, con antecedentes de neurofibromatosis tipo 1 y trauma contuso del ojo derecho desde hace años. Acudió a consulta de oftalmología refiriendo disminución lenta de la visión; al examen físico se constató una agudeza visual de 0.6 en ambos ojos, así como disminución concéntrica del campo visual en la perimetría por confrontación. El examen objetivo mostró en los anexos una pingüécula en ojo derecho y pterigion grado II en ojo izquierdo; en segmento anterior, múltiples nódulos de Lisch en el iris de ambos ojos, y en el ojo derecho, pupila ligeramente midriática, pero reactiva. Se le realizó gonoscopia, oftalmoscopia y perimetría Humphry; en esta última se halló un escotoma arqueado en ojo derecho, y un defecto superior arqueado en el ojo izquierdo. Se concluyó el caso con los diagnósticos de catarata presenil incipiente y glaucoma secundario a neurofibromatosis tipo 1(AU)

A patient aged 59, with a history of neurofibromatosis type 1 and blunt trauma of the right eye for years. He attended ophthalmology consultation referring slow decrease of vision. Physical examination showed visual acuity of 0.6 in both eyes, and decreased concentric visual field by confrontation perimetry. Objective examination showed, in the annexes, a pinguecula in the right eye and grade II pterygium. In the anterior segment, multiple Lisch nodules appeared in the iris of both eyes, and in the right eye a slightly mydriatic but reactive pupil was detected. Gonoscopia, ophthalmoscopy and Humphry perimetry were performed. This last test showed an arcuate scotoma in the right eye and a superior arcuate defect in the left eye. The case was concluded with a diagnosis of incipient presenile cataract and glaucoma secondary to neurofibromatosis type 1(AU)

Targeting tuberculosis and malaria through inhibition of Enoyl reductase: compound activity and structural data.

Tuberculosis and malaria together result in an estimated 5 million deaths annually. The spread of multidrug resistance in the most pathogenic causative agents, Mycobacterium tuberculosis and Plasmodium falciparum, underscores the need to identify active compounds with novel inhibitory properties. Although genetically unrelated, both organisms use a type II fatty-acid synthase system. Enoyl acyl carrier protein reductase (ENR), a key type II enzyme, has been repeatedly validated as an effective antimicrobial target. Using high throughput inhibitor screens with a combinatorial library, we have identified two novel classes of compounds with activity against the M. tuberculosis and P. falciparum enzyme (referred to as InhA and PfENR, respectively). The crystal structure of InhA complexed with NAD+ and one of the inhibitors was determined to elucidate the mode of binding. Structural analysis of InhA with the broad spectrum antimicrobial triclosan revealed a unique stoichiometry where the enzyme contained either a single triclosan molecule, in a configuration typical of other bacterial ENR:triclosan structures, or harbored two triclosan molecules bound to the active site. Significantly, these compounds do not require activation and are effective against wild-type and drug-resistant strains of M. tuberculosis and P. falciparum. Moreover, they provide broader chemical diversity and elucidate key elements of inhibitor binding to InhA for subsequent chemical optimization.