U-Omp19 from Brucella abortus increases dmLT immunogenicity and improves protection against Escherichia coli heat-labile toxin (LT) oral challenge.

Acute diarrhea disease caused by bacterial infections is a major global health problem. Enterotoxigenic Escherichia coli (ETEC) is one of the top causes of diarrhea-associated morbidity and mortality in young children and travelers to low-income countries. There are currently no licensed vaccines for ETEC. Induction of immunity at the site of entry of the bacteria is key to prevent infection. Current approaches to ETEC vaccines include a less toxic mutant form of E. coli heat-labile toxin (double-mutant heat-labile enterotoxin -dmLT-) with both antigenic and immunostimulatory properties. U-Omp19 is a protease inhibitor from Brucella spp. with immunostimulatory properties that has been used as oral adjuvant. In this work, we use U-Omp19 as adjuvant in an oral vaccine formulation against ETEC containing dmLT in outbred and inbred mice. To evaluate antigen dose sparing by U-Omp19 three different immunization protocols with three different doses of dmLT were evaluated. We demonstrated that U-Omp19 co-delivery increases anti-LT IgA in feces using a mid-dose of dmLT following a prime-boost protocol (after one or two boosts). Oral immunization with U-Omp19 induced protection against LT challenge when co-formulated with dmLT in CD-1 and BALB/c mice. Indeed, there was a significant increase in anti-LT IgG and IgA avidity after a single oral administration of dmLT plus U-Omp19 in comparison with dmLT delivered alone. Interestingly, sera from dmLT plus U-Omp19 vaccinated mice significantly neutralize LT effect on intestine inflammation in vivo compared with sera from the group immunized with dmLT alone. These results demonstrate the adjuvant capacity of U-Omp19 to increase dmLT immunogenicity by the oral route and support its use in an oral subunit vaccine formulation against ETEC.

[Akathisia due to risperidone withdrawal: two clinical cases]. / Acatisia por retirada de risperidona: dos observaciones clínicas.

Akathisia due to withdrawal or disruption of antipsychotic treatment is a rare and scarcely elucidated presentation of extrapyramidalism which can also occur after other drug withdrawal. After having reviewed biomedical data basis IME and the latest seven years of MEDLINE and EMBASE, we only found one case, which was published in 1997, of persistent akathisia after risperidone withdrawal, but it had started under treatment with haloperidol. We next present the clinical observation of other two patients who developed akathisia after risperidone withdrawal. In one of them, akathisia started within the first days of treatment at hig-medium doses and got worse after withdrawal; in the other case, akathisia immediately started just after withdrawal of a nine-month treatment with risperidone at low doses.

Acatisia por retirada de risperidona: dos observaciones clínicas / Akathisia due to risperidone withdrawal: two clinical cases

La acatisia por retirada o discontinuación de tratamiento antipsicótico es una presentación rara y poco elucidada de extrapiramidalismo que también puede ocurrir tras la retirada de otros fármacos. Tras revisar las bases de datos biomédicas IME y los últimos siete años de MEDLINE y EMBASE sólo hemos hallado un caso publicado en 1997 de acatisia persistente tras la retirada de risperidona, pero que empezó bajo tratamiento con haloperidol. A continuación presentamos la observación clínica de otros dos pacientes que desarrollaron acatisia tras la supresión de risperidona: en un caso la acatisia había comenzado durante los primeros días del tratamiento con dosis altas-medias y se agravó tras la supresión; en el otro comenzó inmediatamente sólo tras la supresión de un tratamiento de nueve meses de dosis bajas de risperidona (AU)