Tendencia en el consumo de carbapenems en un hospital de asociación público privada / Trend in the consumption of carbapenems in a public-private partnership hospital

Introducción: Los hospitales deben evaluar su consumo de antibióticos y su relación con la resistencia bacteriana local. Objetivo: Identificar la tendencia en el consumo de carbapenems y explorar su correlación con cultivos de Pseudomona aeruginosa multirresistente. El estudio: Estudio ecológico realizado en un hospital de Lima ­ Perú. Se midió el consumo de imipenem y meropenem en un año y calculó la correlación con cultivos de Pseudomona aeruginosa multirresistente. Hallazgos: El consumo de imipenem no tuvo variaciones relevantes y el de meropenem tuvo tendencia a disminuir. La frecuencia de cultivos con Pseudomona aeruginosa multirresistente fue baja y con leve tendencia a la disminución. Hubo correlación significativa positiva entre la dosis diaria definida de meropenem según estancia y egresos hospitalarios con cultivos de Pseudomona aeruginosa multirresistente (0,71, p=<0,01 y 0,64, p=0,02, respectivamente). Conclusión: Hubo tendencia a la disminución y correlación significativa en el consumo de meropenem y cultivos de Pseudomona aeruginosa multirresistente.

Background:Hospitalsshouldevaluatetheirantibioticsuseandthe relationship with local bacterial resistance. Identify the trend in Objective:the consumption of carbapenems and explore its correlation with multiresistant Pseudomona aeruginosacultures. The study: An ecological study was carried out in a hospital in Lima ­ Peru. We measured the consumption of imipenem and meropenem in one year and calculated the correlation with multiresistant Pseudomona aeruginosacultures. The consumption of imipenem had Findings:no significant variations, but meropenem had a tendency to decrease. There was a significant positive correlation between the defined daily dose of meropenem according to hospital stay and discharges with multiresistant Pseudomona aeruginosacultures (0.71, p=<0.01 and 0.64, p=0.02, respectively). Conclusion:There was a downward trend in the consumption of meropenem and this had a significant correlation with the decrease in multiresistant Pseudomona aeruginosacultures

PKC-δ activation in neutrophils promotes fungal clearance.

The C-type lectin receptor dectin-1 and the integrin Mac-1 have key roles in controlling fungal infection. Here, we demonstrate that dectin-1- and Mac-1-induced activation of protein kinase Cδ in neutrophils, independent of the Card9 adaptor, is required for reactive oxygen species production and for intracellular killing upon Candida albicans uptake. Protein kinase Cδ was also required for zymosan-induced cytokine generation in neutrophils. In macrophages, protein kinase Cδ deficiency prevented fungi-induced reactive oxygen species generation but had no effect on activation of TGF-ß-activated kinase-1, an effector of Card9, or nuclear factor κB activation, nor did it affect phagolysosomal maturation, autophagy, or intracellular C. albicans killing. In vivo, protein kinase Cδ-deficient mice were highly susceptible to C. albicans and Aspergillus fumigatus infection, which was partially rescued with adoptively transferred wild-type neutrophils. Thus, protein kinase Cδ activation downstream of dectin-1 and Mac-1 has an important role in neutrophil, but not macrophage, functions required for host defense against fungal pathogens.

Identifying Yersinia YopH-targeted signal transduction pathways that impair neutrophil responses during in vivo murine infection.

Identifying molecular targets of Yersinia virulence effectors, or Yops, during animal infection is challenging because few cells are targeted by Yops in an infected organ, and isolating these sparse effector-containing cells is difficult. YopH, a tyrosine phosphatase, is essential for full virulence of Yersinia. Investigating the YopH-targeted signal transduction pathway(s) in neutrophils during infection of a murine host, we find that several host proteins, including the essential signaling adaptor SLP-76, are dephosphorylated in the presence of YopH in neutrophils isolated from infected tissues. YopH inactivated PRAM-1/SKAP-HOM and the SLP-76/Vav/PLCγ2 signal transduction axes, leading to an inhibition of calcium response in isolated neutrophils. Consistent with a failure to mount a calcium response, IL-10 production was reduced in neutrophils containing YopH from infected tissues. Finally, a yopH mutant survived better in the absence of neutrophils, indicating that neutrophil inactivation by YopH by targeting PRAM-1/SKAP-HOM and SLP-76/Vav/PLCγ2 signaling hubs may be critical for Yersinia survival.

The presence of professional phagocytes dictates the number of host cells targeted for Yop translocation during infection.

Type III secretion systems deliver effector proteins from Gram-negative bacterial pathogens into host cells, where they disarm host defences, allowing the pathogens to establish infection. Although Yersinia pseudotuberculosis delivers its effector proteins, called Yops, into numerous cell types grown in culture, we show that during infection Y. pseudotuberculosis selectively targets Yops to professional phagocytes in Peyer's patches, mesenteric lymph nodes and spleen, although it colocalizes with B and T cells as well as professional phagocytes. Strikingly, in the absence of neutrophils, the number of cells with translocated Yops was significantly reduced although the bacterial loads were similar, indicating that Y. pseudotuberculosis did not arbitrarily deliver Yops to the available cells. Using isolated splenocytes, selective binding and selective targeting to professional phagocytes when bacteria were limiting was also observed, indicating that tissue architecture was not required for the tropism for professional phagocytes. In isolated splenocytes, YadA and Invasin increased the number of all cells types with translocated Yops, but professional phagocytes were still preferentially translocated with Yops in the absence of these adhesins. Together these results indicate that Y. pseudotuberculosis discriminates among cells it encounters during infection and selectively delivers Yops to phagocytes while refraining from translocation to other cell types.

Borrelia burgdorferi BBB07 interaction with integrin alpha3beta1 stimulates production of pro-inflammatory mediators in primary human chondrocytes.

Borrelia burgdorferi, the causative agent of Lyme disease, activates multiple signalling pathways leading to induction of pro-inflammatory mediators at sites of inflammation. Binding of B. burgdorferi to integrin alpha(3)beta(1) on human chondrocytes activates signalling leading to release of several pro-inflammatory mediators, but the B. burgdorferi protein that binds integrin alpha(3)beta(1) and elicits this response has remained unknown. A search of the B. burgdorferi genome for a canonical integrin binding motif, the RGD (Arg-Gly-Asp) tripeptide, revealed several candidate ligands for integrins. In this study we show that one of these candidates, BBB07, binds to integrin alpha(3)beta(1) and inhibits attachment of intact B. burgdorferi to the same integrin. BBB07 is expressed during murine infection as demonstrated by recognition by infected mouse sera. Recombinant purified BBB07 induces pro-inflammatory mediators in primary human chondrocyte cells by interaction with integrin alpha(3)beta(1). This interaction is specific, as P66, another integrin ligand of B. burgdorferi, does not activate signalling through alpha(3)beta(1). In summary, we have identified a B. burgdorferi protein, BBB07, that interacts with integrin alpha(3)beta(1) and stimulates production of pro-inflammatory mediators in primary human chondrocyte cells.

Granzyme B binds to target cells mostly by charge and must be added at the same time as perforin to trigger apoptosis.

Perforin (PFN) delivery of granzymes (Gzm) into the target cell at the immunological synapse is the major pathway for inducing apoptosis of virus-infected cells and tumors. A validated model for how PFN delivers Gzm into the cytosol is still lacking. PFN was originally thought to work by forming pores in the target cell plasma membrane that allow Gzm entry. This model was questioned when it was shown that GzmB is endocytosed without PFN. Moreover, apoptosis could be triggered by adding PFN to washed cells that have previously endocytosed GzmB. In this study, we show that GzmB binds to the plasma membrane mostly via nonspecific charge interactions. Washing in saline does not remove bound Gzm. However, if externally bound GzmB is completely removed, subsequent addition of PFN does not release previously endocytosed GzmB and does not trigger apoptosis. Therefore, PFN must be coendocytosed with GzmB to deliver it into the cytosol.

El paciente post-operatorio en el área de pacientes graves de emergencia / The post-operated patient in the urgency critical ill area

Durante el año de 1989 fueron admitidos 209 pacientes en el Area de Pacientes Graves de Emergencia. Cuarenta y ocho (23 por ciento) ingresaron a nuestra área luego de un procedimiento quirúrgico mayor de emergencia con la finalidad de recibir terapia activa y/o monitoreo post-operatorio. El tiempo promedio de estancia fue 8 (1-20) días. La edad promedio 48 (16-76) años y treinta y siete (77 por ciento) fueron hombres. El puntaje APACHE II promedio fue 17 (15-20) y el TISS promedio 26 (24-33). Fallecieron 15 (31 por ciento) enfermos. La categoría diagnóstica más frecuente fue: shock hemorrágico-hipovolémico en 13 casos, sepsis post-operatoria en 10 y craneotomía en 9 entre otras. La población post-operada constituye la cuarta parte del global manejado en esta área con un tiempo de hospitalización prolongado. Esta es una situación sui géneris que requiere corrección a corto plazo. Se recomienda que los enfermos sometidos a un procedimiento quirúrgico de emergencia como los referidos no deberían hacer el post-operatorio en una sala de hospitalización de emergencia

El paciente respiratorio crítico en una sala de hospitalización de emergencia / Critical respiratory patient in an emergency unit

Durante el año 1989 registramos próspectivamente los casos graves con compromiso respiratorio evaluados en el Servicio de Emergencia del Hospital Nacional Guillermo Almenara Irigoyen. La población evaluada incluye 72 pacientes adultos sin enfermedad gíneco-obstétrica. Fueron 56 hombres (78 por ciento) con edad promedio de 52 (15-69) años. Las causas más frecuentes de compromiso respiratorio fueron: enfermedad vascular cerebral 17 (24 por ciento), traumatismo encéfalo craneano 10 (14 por ciento), neumonía 10 (14 por ciento), sepsis 9 (13 por ciento) y asma bronquial 7 (10 por ciento). El status asmático y la neumonía nosocomial fueron primera causa de Insuficiencia Respiratoria Ventilatoria y Oxigenatoria respectivamente. Sepsis fue el factor que con más frecuencia desencadenó el SDRA. El valor APACHE II promedio fué 21 (18-23) y el TISS 24 (20-26). La mortalidad global fué 49 por ciento (35/72) y estuvo por encima de la esperada de acuerdo al puntaje APACHE II. Las causas de este hallazgo deben ser investigadas. Todos los enfermos con SDRA fallecieron. El Hospital Guillermo Almenara Irigoyen requiere una Unidad de Cuidados Intensivos

Algunos aspectos de la comercialización de drogas de la medicina tradicional / Some aspects of the commercialization of drugs from the traditional medicine

Se realiza un estudio de distintas formas tradicionales y modernas para la presentación en el mercado de las drogas de origen vegetal. Se compatibilizan estas formas comerciales con las normas para la conservación y estabilidad de los principios activos. Se hacen algunas recomendaciones con fines comerciales