RESUMEN
The growing importance of submicrometer-structured surfaces across a variety of different fields has driven progress in light manipulation, color diversity, water-repellency, and functional enhancements. To enable mass production, processes like hot-embossing (HE), roll-to-roll replication (R2R), and injection molding (IM) are essential due to their precision and material flexibility. However, these processes are tool-based manufacturing (TBM) techniques requiring metal molds, which are time-consuming and expensive to manufacture, as they mostly rely on galvanoforming using templates made via precision microlithography or two-photon-polymerization (2PP). In this work, a novel approach is demonstrated to replicate amorphous metals from fused silica glass, derived from additive manufacturing and structured using hot embossing and casting, enabling the fabrication of metal insets with features in the range of 300 nm and a surface roughness of below 10 nm. By partially crystallizing the amorphous metal, during the replication process, the insets gain a high hardness of up to 800 HV. The metal molds are successfully used in polymer injection molding using different polymers including polystyrene (PS) and polyethylene (PE) as well as glass nanocomposites. This work is of significant importance to the field as it provides a production method for the increasing demand for sub-micron-structured tooling in the area of polymer replication while substantially reducing their cost of production.
RESUMEN
Chlamydia trachomatis serovars D-K are one of the most frequent causes of sexually transmitted infections of the female genital tract, with possible complications such as hydrosalpinx, pelvic inflammatory disease, extra-uterine gravidity or infertility. We used the murine genital tract infection model with C. muridarum for vaccination studies and found that more than 70% of the infected mice suffered from uterus dilatations and/or hydrosalpinx. Systemic consequences of the vaginal infection were apparent by splenomegaly ten to fifteen days post infection. While cultivable microorganisms were detectable for the first 23days post infection, the first lesions of the genital tract developed at day 15, however, many lesions occurred later in the absence of cultivable bacteria. Lesions were not accompanied by pro-inflammatory cytokines such as IFNÉ£, TNF and IL-6, since these cytokines were almost undetectable in the genital tract 43days post infection. To prevent genital tract lesions, we vaccinated mice with the polymorphic membrane protein (Pmp) A in combination with CpG-ODN 1826 as adjuvant. The vaccine lowered the chlamydial burden and the differences were significant at day 10 post infection but not later. More importantly the vaccine decreased the rate and severity of genital tract lesions. Interestingly, control vaccination with the protein ovalbumin plus CpG-ODN 1826 enhanced significantly the severity but not the rate of pathologic lesions, which was presumably caused by the activation of innate immune responses by the adjuvant in the absence of a C. muridarum-specific adaptive immune response. In summary, vaccination with recombinant PmpA plus CpG-ODN 1826 significantly reduced C. muridarum-induced tissue damage, however, CpG-ODN 1826 may aggravate C. muridarum-induced tissue injuries in the absence of a protective antigen.
Asunto(s)
Vacunas Bacterianas/inmunología , Infecciones por Chlamydia/patología , Infecciones por Chlamydia/prevención & control , Chlamydia muridarum/inmunología , Enfermedades de los Genitales Femeninos/patología , Enfermedades de los Genitales Femeninos/prevención & control , Proteínas de la Membrana/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Proteínas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Infecciones por Chlamydia/microbiología , Modelos Animales de Enfermedad , Femenino , Enfermedades de los Genitales Femeninos/microbiología , Ratones Endogámicos C57BL , Oligodesoxirribonucleótidos/administración & dosificación , Resultado del Tratamiento , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunologíaRESUMEN
The present study aimed to determine the relevance of cyclooxygenase-2 (COX-2)-derived prostanoids for the adverse effects of lipopolysaccharides (LPSs) on cardiovascular function. For this goal, male Sprague-Dawley rats received a single intravenous dose of LPS (10 mg/kg) and were treated with different cyclooxygenase inhibitors. Injection of LPS caused a marked decrease of systolic arterial pressure, from 128 to 79 mm Hg, and a concomitant increase of heart rate, from 380 to 530 minutes(-1). Both the decrease of systemic arterial pressure and the increase of heart rate induced by LPS were almost absent if the animals also received the COX-2 blocker rofecoxib (20 mg/kg), regardless whether the drug was given 1 hour before or 1 hour after LPS. Although plasma and organ levels of prostanoids were lowered by rofecoxib, the characteristic LPS-induced increases of NO synthase II and COX-2 gene expression, as well as of plasma and tissue nitrate/nitrite concentrations, were not affected by rofecoxib. Although rofecoxib treatment did also not change LPS-induced tissue cytokine concentrations, it markedly improved LPS-induced liver damage, as indicated by the decrease of transaminases. Moreover, the overall well-being of the LPS-injected animals improved on concomitant treatment with the COX-2 inhibitor. Taken together, our data suggest that COX-2-derived prostanoids are major mediators for the detrimental effects of LPS on cardiovascular and organ function.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Inhibidores de la Ciclooxigenasa/farmacología , Isoenzimas/antagonistas & inhibidores , Lipopolisacáridos , Animales , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/inducido químicamente , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Citocinas/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Expresión Génica/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Inyecciones Intravenosas , Isoenzimas/genética , Isoenzimas/metabolismo , Lactonas/farmacología , Masculino , Proteínas de la Membrana , Nitratos/metabolismo , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Nitritos/metabolismo , Prostaglandina-Endoperóxido Sintasas/genética , Prostaglandina-Endoperóxido Sintasas/metabolismo , Prostaglandinas/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Sulfonas , Transaminasas/sangreRESUMEN
On the basis of recent evidence that the cyclooxygenase-2 (COX-2) gene promoter contains functional binding sites for the nuclear factor of activated T cells (NFAT) and that COX-2 is expressed in a regulated fashion in the kidney, this study aimed to assess the effect of immunosuppressants on COX-2 expression in the kidney. Therefore, Wistar-Kyoto rats were treated with cyclosporine A (CsA; 15 mg/kg per day) or tacrolimus (5 mg/kg per day) for 7 d each. Both drugs markedly lowered COX-2 expression while COX-1 expression remained unaltered. Furthermore, CsA blunted the increase of renocortical COX-2 expression in response to low salt intake or a combination of low-salt diet with the ACE inhibitor ramipril (10 mg/kg per day), which strongly stimulates renocortical COX-2 expression. At the same time, calcineurin inhibitors moderately enhanced basal as well as stimulated renin secretion and renin gene expression. These findings suggest that inhibition of calcineurin could be a crucial determinant for the regulated expression of COX-2 in the kidney. Inhibition of COX-2 expression may therefore at least in part account for the well-known adverse effects of immunosuppressants in the kidney. Moreover, our data suggest that the stimulation of the renin system by low salt and by ACE inhibitors is not essentially mediated by COX-2 activity.