[Translated article] Experience in major complications with total trapezometacarpal prostheses.

INTRODUCTION: The treatment of rhizarthrosis using trapeziometacarpal prostheses (TMP) is increasing. Complications may lead to loss of the implant and result in salvage surgery. Our aim was to assess major complications with the use of some TMP models and their rescue. MATERIAL AND METHOD: Retrospective study on TMP implanted between 2006 and 2021. Models studied: Arpe®, Elektra®, Ivory®, Maïa®, Isis® and Touch®. Demographic data were assessed, implant placement by radiographic study, technical data, complications, salvage surgeries and final survival. RESULTS: Review of 224 TMP, 45 Arpe® (95.5% survival, rate follow-up [R] 6-16 years), 5 Elektra® (80% survival, R 13-14), 14 Ivory® (92.8% survival, R 9-11), 7 Maïa® (100% survival, R 8-9), 115 Isis® (99.1% survival, R 1-8), 38 Touch® (100% survival, R 1-4). The medial angle of the dome with the proximal articular surface of the trapezium in the lateral plane, was: Arpe®: 8.85°, Elektra®: not assessable, Ivory®: 6.6°, Maïa®: 14.4°, Isis®: 3.8°, and Touch®: 5.95°. The Isis® was placed 100% with scopic guidance presenting a significantly lower angle respect to the medial angle of the dome with the proximal articular surface of the trapezium. As main complications, we observed 3.5% of dislocations and 4% of mobilisations, with the Elektra® being responsible for 47% of these. Nineteen salvage surgeries were performed, with 3% of the implants being lost. CONCLUSIONS: Dislocation and mobilisation are the most observed complications, the Elektra® responsible for almost half of them. Correct placement and implant design appear to be crucial to avoid them in the short and long term.

Experience in major complications with total trapezometacarpal prostheses. / Experiencia en complicaciones mayores con las prótesis totales trapeciometacarpianas.

INTRODUCTION: The treatment of rhizarthrosis using trapeziometacarpal prostheses (TMP) is increasing. Complications may lead to loss of the implant and result in salvage surgery. Our aim was to assess major complications with the use of some TMP models and their rescue. MATERIAL AND METHOD: Retrospective study on TMP implanted between 2006 and 2021. Models studied: Arpe®, Elektra®, Ivory®, Maïa®, Isis® and Touch®. Demographic data were assessed, implant placement by radiographic study, technical data, complications, salvage surgeries and final survival. RESULTS: Review of 224 TMP, 45 Arpe® (95.5% survival, rate follow-up [R] 6-16 years), 5 Elektra® (80% survival, R 13-14), 14 Ivory® (92.8% survival, R 9-11), 7 Maïa® (100% survival, R 8-9), 115 Isis® (99.1% survival, R 1-8), 38 Touch® (100% survival, R 1-4). The medial angle of the dome with the proximal articular surface of the trapezium in the lateral plane, was: Arpe®: 8.85°, Elektra®: not assessable, Ivory®: 6.6°, Maïa®: 14.4°, Isis®: 3.8°, and Touch®: 5.95°. The Isis® was placed 100% with scopic guidance presenting a significantly lower angle respect to the medial angle of the dome with the proximal articular surface of the trapezium. As main complications, we observed 3.5% of dislocations and 4% of mobilisations, with the Elektra® being responsible for 47% of these. Nineteen salvage surgeries were performed, with 3% of the implants being lost. CONCLUSIONS: Dislocation and mobilisation are the most observed complications, the Elektra® responsible for almost half of them. Correct placement and implant design appear to be crucial to avoid them in the short and long term.

Initial survival of the Isis® total trapeziometacarpal prosthesis with conical trunk threaded cups. / Supervivencia inicial de la prótesis total trapeciometacarpiana de cúpula roscada Isis®.

INTRODUCTION: The treatment of trapeziometacarpal osteoarthritis through the implantation of total trapeziometacarpal prostheses is in continuous expansion. The Isis® prosthesis is a trunk-conical threaded anchorage prosthesis. Our objective was to assess the functional results and survival of this implant for at least one year of follow-up. MATERIAL AND METHOD: Prospective study on 53 Isis® prosthesis, implanted from april 2014 to january 2019. The Van Cappelle functional test, pain, strength, mobility, return to previous activity, radiological variables and placement of the trapezial component were evaluated. The surgical technique was performed with a guide wirefocused on the trapezius and control of the scopia. Observed complications were recorded and statistical analysis was performed. RESULTS: Fifty-one implants (49 patients) were reviewed. Mean follow-up was 2.1 years (1-5.7). Van Cappelle's test, pain, mobility, and grip and clamp strength improved significantly, as did the distance between the metacarpal head and the trapezius base; 96% of the patients returned in less than 6 months to their activities. Minor complications, 3 De Quervain's tendinopathy and 2 intra-operative metacarpal and 2 trapezium fractures were recorded, and one carpal tunnel syndrome. There was no dislocation, mobilization, or implant infection. CONCLUSIONS: The functional results of the Isis® prosthesis are excellent in the short term, far exceeding the first year of 100% of survival. The complications that arose were minor and few. The anchorage and placement of the trapezial component guided by scopia seem to be crucial for the good result.

Total thumb carpometacarpal arthroplasty for failed trapeziometacarpal joint arthrodesis.

Trapeziometacarpal joint arthrodesis is a surgical option for osteoarthritis of the first carpometacarpal joint; however, it has well-known disadvantages such as non-union and reduced mobility. Revision procedures are often not discussed and lack consensus. We are reporting two cases of satisfactory thumb implant arthroplasty for failed trapeziometacarpal joint arthrodesis in order to discuss the surgical technique, its advantages compared with other surgical options and therefore its potential indications.

Factores que influyen sobre los resultados de los ensayos de ultra-microindentación ósea. Un estudio experimental en ratas / Factors that influence the results of bone ultra-microindentation tests. An experimental study in rats

OBJETIVO: Las propiedades de los materiales que constituyen el tejido óseo son determinantes en su resistencia mecánica pero los factores que influyen sobre ella son parcialmente desconocidos en la actualidad. MATERIAL Y MÉTODOS: En esta investigación medimos la dureza ósea mediante ensayos de ultra-microindentación con punta tipo Berkovich y una carga de 150 mN en fémures de ratas Sprague-Dawley sometidas a una fractura transversal o a una osteotomía de sustracción, y comparamos los resultados en diferentes localizaciones óseas y grupos experimentales. El estudio comprende los siguientes cuatro grupos experimentales, cada uno de ellos constituido por cuatro ratas: a) fractura diafisiana estándar; b) fractura más osteotomía de 2 mm; c) osteotomía tratada con hormona paratiroidea humana, PTH (1-84); d) osteotomía tratada con ranelato de estroncio. RESULTADOS: Encontramos que la dureza del material era consistentemente mayor en el hueso cortical que en el hueso trabecular. También fue consistentemente más alto en las epífisis femorales superiores que en las epífisis inferiores (diferencia de 1,2 desviaciones estándar). La cirugía redujo la dureza en el fémur operado (diferencia de 0,3 desviaciones estándar, p = 5,5 x 10-2). El tratamiento con PTH indujo un aumento leve pero consistente de la dureza en todos los sitios (p = 1,8 × 10-5) mientras que el efecto del ranelato de estroncio fue inconsistente. CONCLUSIONES: Estos datos muestran que la microdureza tisular está influida por una variedad de factores, incluyendo la anatomía, el tipo de tejido óseo, la lesión esquelética y la terapia farmacológica. Por lo tanto, los estudios futuros sobre la calidad del tejido deberían diseñarse cuidadosamente teniendo en cuenta estos factores

OBJETIVE: The properties of the materials that constitute the bone tissue are decisive in its mechanical strength but the factors that influence it are partially unknown at present. Material and method: In this paper, we gauge bone hardness by means of ultra-microindentation tests with a Berkovich tip and a 150 mN load in femurs of Sprague-Dawley rats subjected to a transverse fracture or a subtraction osteotomy. The results are compared in different bone locations and experimental groups. The study includes the following four experimental groups, each consisting of four rats: a) standard diaphyseal fracture; b) fracture plus osteotomy of 2 mm; c) osteotomy treated with human parathyroid hormone, PTH (1-84); d) osteotomy treated with strontium ranelate. RESULTS: We found the hardness of the material was consistently greater in cortical bone than in trabecular bone. It was also consistently higher in the upper femoral epiphyses than in the lower epiphyses (difference of 1.2 standard deviations). The surgery reduced hardness in the operated femur (difference of 0.3 standard deviations, p = 5.5 x 10-2). PTH treatment induced a slight but consistent increase in hardness at all sites (p = 1.8 x 10-5) while the effect of strontium ranelate was inconsistent. CONCLUSIONS: These data show that tissue micro-hardness is influenced by a variety of factors, including anatomy, type of bone tissue, skeletal injury and drug therapy. Therefore, future studies on tissue quality should be carefully designed with these factors in mind

Comparative study of the effect of PTH (1-84) and strontium ranelate in an experimental model of atrophic nonunion.

UNLABELLED: This study aimed to set up an experimental model of long bone atrophic nonunion and to explore the potential role of PTH-1-84 (PTH 1-84) and strontium ranelate (SrR). A model of atrophic nonunion was created in Sprague-Dawley rats at the femoral midshaft level. The animals were randomised into four groups. Group A1: control rodents, fracture without bone gap; Group A2: rodents with subtraction osteotomy (non-union model control) treated with saline; Group B: rodents with subtraction osteotomy treated with human-PTH (PTH 1-84); and Group C: rodents with subtraction osteotomy treated with strontium ranelate (SrR). The groups were followed for 12 weeks. X-rays were be obtained at weeks 1, 6 and 12. After sacrificing the animals, we proceeded to the biomechanical study and four point bending tests to evaluate the resistance of the callus and histological study. In second phase, the expression of genes related to osteoblast function was analysed by reverse transcription-quantitative PCR in rats subjected to substraction osteotomy and treated for 2 weeks. The animals were randomised into three groups: Group A2: rodents treated with saline; Group B: rodents treated with PTH 1-84 and Group C: rodents treated with SrR. RESULTS: No significant histological differences were found between animals subjected to subtraction osteotomy and treated with either saline or PTH (p=0.628), but significant difference existed between animals receiving saline or SrR (p=0.005). There were no significant differences in X-ray score between the saline and PTH groups at either 6 or 12 weeks (p=0.33 and 0.36, respectively). On the other hand, better X-ray scores were found in the SrR group (p=0.047 and 0.006 in comparison with saline, at 6 and 12 weeks, respectively). In line with this, biomechanical tests revealed improved results in the SrR group. Gene expression analysis revealed a slightly decreased levels of DKK1, a Wnt pathway inhibitor, in rats treated with SrR. CONCLUSIONS: SrR increases has a beneficial effect in this atrophic non-union model in rats. This suggests that it might have a role may have important implications for the potential clinical role in the treatment of fracture nonunion.

Distal radius fractures: Should we use supplemental bone grafts or substitutites in cases of severe osteoporotic or conminution?

OBJECTIVES: The purpose of this study was to assess the need of bone graft or bone substitutes in unstable distal radius fractures (DRF) treated with locking compression plates (LCP) PATIENTS AND METHODS: An observational and prospective study was conducted on 60 patients with DRF AO-type A3 and AO-type C3, treated surgically by LCP plates without bone grafts or substitutes. Ranges of motion in flexion (F), extension (E), pronation (P), and supination (S) were measured in the injured wrist and compared with the healthy contralateral wrist. X-ray parameters: palmar tilt (PT), radial inclination (RI), ulnar variance (UV), and radial height (RH) were calculated in the injured wrist one year after surgery and then compared, with those parameters in the healthy contralateral wrist and in the follow-up postoperative x-ray of the injured wrist. PRWE and DASH scores were used to evaluate patient satisfaction. RESULTS: The range of motion loss was F 12° ± 16.1°, E 9° ± 13.1°, P 2.5° ± 7.5°, and S 5°±10°, but they remained within functional parameters. Good results were also obtained in the PRWE and DASH scores (DASH 12.6 ± 14.16 and PRWE 9.5 ± 9.5). All the fractures were healed without significant collapse (IP 0.55 ± 1.7°, IR 0.31 ± 1.5°, VC 0.25±0.8mm, and AR 0.1 ± 0.9 mm). CONCLUSIONS: All fractures healed without problems or with significant loss of reduction. Bone graft and bone substitutes are not mandatory for treatment of unstable DRF with LCP plates. Their use increases the cost and is not exempt of morbidities. This study also reinforces the role of LCP plates in surgical treatment of unstable DRF.

Reproductive aspects of the yellowtail snapper Ocyurus chrysurus from the southern Gulf of Mexico.

In this study, sex ratio, spawning season, fork length (L(F)) at maturity (L(F50)), batch fecundity and spawning frequency were characterized for the continental population of Ocyurus chrysurus from the Campeche Bank, in the southern Gulf of Mexico. A total of 1657 specimens were collected from February 2008 to January 2009. The overall sex ratio (male:female) and sex ratios by size-class showed no significant differences from an expected 1:1 ratio. The Campeche Bank population did not conform to the reproductive seasonality pattern characteristic of a continental population. A protracted spawning season that extended from January to September with peaks occurring mainly between April and May and additionally in September was observed. The population conformed, however, to the sexual maturity pattern observed for populations and species associated with a continental margin. Fish of both sexes reached the onset of sexual maturity at a similar and small L(F) of c. 14 cm, and L(F50) (L(F) at which 50% of females and males become mature) was 21·3 and 19·4 cm. Asynchronous-type ovarian development was observed for this species and batch fecundity estimates ranged from 14,102 to 164,756 oocytes (mean ±S.D. = 43,852 ± 32,684 oocytes). The overall spawning frequency estimate was once every 8·3 days or 26 times during the 9 month spawning season.

Resultados funcionales y complicaciones de las placas volares bloqueadas de radio distal / Functional results and complications of locked distal radius volar plates

Introducción y objetivos: En los últimos años se está observando un aumento en la intensidad del tratamiento de la fractura de radio distal derivado hacia la fijación interna. Las placas bloqueadas evitan el colapso metafisario aun con el hueso osteoporótico o conminuto, mantienen la reducción y permiten una movilidad temprana. Sin embargo, todavía no hay suficiente evidencia de cuál es el mejor método de tratamiento para esta fractura. Nuestro objetivo es evaluar nuestro resultado funcional y las complicaciones con el uso de las placas bloqueadas de radio distal. Material y métodos: Estudio retrospectivo sobre 145 fracturas inestables de radio distal tratadas mediante placa volar bloqueada, con un seguimiento medio de 28 meses. Se usó la clasificación AO (Asociación para el Estudio de la Osteosíntesis) y la clasificación de Fernández. Se evaluó la presencia de osteoporosis, la necesidad de injerto, la diferencia de movilidad entre la muñeca sana y la muñeca fracturada y las medidas radiográficas, así como el test funcional PRWE (Patient–Rated Wrist Evaluation) y las complicaciones. Análisis estadístico. Resultados: Se revisó a 95 pacientes. La puntuación media del PRWE fue de 13 puntos. Se encontró una relación significativa entre la movilidad y el resultado funcional. Se utilizó injerto en 3 pacientes y no hubo casos de seudoartrosis o colapsos metafisarios. El 8% de los pacientes presentó alguna complicación seria (algodistrofia, dolor crónico o consolidación viciosa). Conclusiones: Las placas bloqueadas se presentan como una alternativa para el tratamiento de las fracturas inestables de radio distal, proporcionan buenos resultados funcionales, pocas complicaciones, minimizan la necesidad de aporte de injerto y permiten una movilización temprana aun con hueso osteoporótico o conminuto (AU)

Introduction and purpose: In the last few years, there has been increased aggressiveness in the treatment of distal radius fractures by means of internal fixation. Locked plates prevent metaphyseal collapse even in the presence of osteoporotic or comminuted bone; they also maintain reduction and allow early motion. Nevertheless, there is as yet not enough evidence as to what may be the best way of treating this fracture. Our purpose is to assess our functional results and the complications that can arise from the use of distal radius locked plates. Materials and methods: This is a retrospective study of 145 unstable distal radius fractures treated by means of a locked volar plate, with a mean follow-up of 28 months. AO (Association for the Study of Osteosynthesis) and Fernandez’ classifications were used to assess the presence of osteoporosis, need for a graft, difference between healthy and fractured hand in terms of mobility, the radiographic measurements and the functional PRWE (Patient-Rated Wrist Evaluation) test and any potential complications. A statistical analysis was carried out.Results95 patients were analyzed. Mean PRWE score was 13 points. A significant relation was found between motion and functional result. A graft was used in 3 patients and there were no cases of pseudoarthrosis or metaphyseal collapses. Eight percent of patients presented with some serious complication (algodystrophy, chronic pain, malunion). Conclusions: Locked plates can be regarded as an alternative to the treatment of unstable distal radius fractures. They provide good functional results and few complications, they minimize the need for grafting and they allow early mobilization even in the presence of osteporotic and comminute bone (AU)

Neumonía lipoidea endógena asociada a enfisema / No disponible

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Brucella lipopolysaccharides induce cyclooxygenase-2 expression in monocytic cells.

Human brucellosis is characterized by the presence of both acute inflammatory episodes and chronic inflammation with granuloma formation. On this basis, the proinflammatory effects of smooth lipopolysaccharide of Brucella (S-LPS) were addressed and compared to those of LPS from Escherichia coli. For this purpose, the induction of cyclooxygenase-2 (COX-2), the production of the chemokine monocyte chemoattractant protein-1 (MCP-1), and the activation of the nuclear factor kappa B (NF-kappa B) were studied. S-LPS was found to induce both COX-2 expression and MCP-1 production; however, the potency of E. coli LPS exceeded that of Brucella S-LPS by some orders of magnitude. However, at concentrations above 1 microg/ml, all of the LPS produced comparable effects, including their ability to activate the NF-kappa B system. These observations help explain the inflammatory events associated with Brucella infection and the ability of Brucella to produce monocyte recruitment and granuloma formation.

Efectos del triflusal y la aspirina sobre los mediadores inflamatorios cardiovasculares inducidos por NF- kB / Effects of trifusal and aspirin over imflamatory cardiovascular mediators mediated by NF-kB

El factor de transcripción nuclear NF-kB controla la expresión de diversos genes implicados en la patogénesis de la ateroclerosis. El triflusal (ácido 2-acetoxi-4-trifluorometilbenzoico) es un fármaco antiagregante que, aunque relacionado estructuralmente con la aspirina y otros salicilatos, muestra un perfil farmacológico y farmacocinético característico. Dado que recientemente se ha demostrado que los salicilatos pueden inhibir el NF-kB, el objetivo del presente estudio ha sido probar la actividad inhibitoria tanto del triflusal como de su metabolito desacetilado, el HTB, sobre la activación de NF-kB. Los resultados aquí descritos muestran que ambos compuestos, trifulsal y HTB, son inhibidores de la activación de NF-kB más potentes que la aspirina o el salicilato, y como consecuencia de ello, pueden bloquear la inducción de la síntesis de citocinas (TNF-a), quimiocinas (MCP-1), moléculas de adhesión (VCAM-1) y enzimas proinflamatorios (COX-2, NOS 2).Además, a diferencia de la aspirina, estos efectos antiinflamatorios del trifulsal se alcanzan a concentraciones similares a las obtenidas en su uso terapeútico como fármaco antiagregante plaquetario. El trifulsal puede ejercer efectos antiinflamatorios en trastornos cardiovasculares en los que se ha observado que genes controlados por el NF-kB están sobrexpresados (AU)

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Cytosolic phospholipase A2 and the distinct transcriptional programs of astrocytoma cells.

Astrocytes constitute the most abundant cell type in the nervous system. Under physiological conditions, they respond to the stimuli to which neurons are also responsive. The use of astrocytoma cell lines with well-defined morphological and functional markers has been helpful for addressing the mechanisms of signal transduction that operate in the nervous system. On the basis of the effects produced by agonists of different types of receptor (muscarinic ACh receptors, thrombin receptors, phospholipases A2 receptors and tumor necrosis factor alpha receptors), several different transcriptional programs that involve the MAP kinase-cytosolic phospholipase A2 system and the transcription factor NF-kappaB have been described.

Lipopolysaccharides of Brucella abortus and Brucella melitensis induce nitric oxide synthesis in rat peritoneal macrophages.

Smooth lipopolysaccharide (S-LPS) and lipid A of Brucella abortus and Brucella melitensis induced the production of nitric oxide (NO) by rat adherent peritoneal cells, but they induced lower levels of production of NO than Escherichia coli LPS. The participation of the inducible isoform of NO synthase (iNOS) was confirmed by the finding of an increased expression of both iNOS mRNA and iNOS protein. These observations might help to explain (i) the acute outcome of Brucella infection in rodents, (ii) the low frequency of septic shock in human brucellosis, and (iii) the prolonged intracellular survival of Brucella in humans.

Signaling mechanisms involved in the activation of arachidonic acid metabolism in human astrocytoma cells by tumor necrosis factor-alpha: phosphorylation of cytosolic phospholipase A2 and transactivation of cyclooxygenase-2.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that elicits cell responses by activating the mitogen-activated protein kinase (MAP kinase) cascade and transcription factors such as nuclear factor-kappaB (NF-kappaB). As these elements play a central role in the mechanisms of signaling involved in the activation of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2), the effect of TNF-alpha on arachidonate (AA) metabolism in 1321N1 astrocytoma cells was assayed. TNF-alpha produced a phosphorylation of cPLA2, which was preceded by an activation of both c-Jun N-terminal kinase (JNK) and p38-MAP kinase, and this was associated with the release of [3H]AA. In contrast, TNF-alpha did not activate the extracellular signal-regulated kinase (MAP kinase) p42, nor did it elicit a mitogenic response. Analysis of [3H]AA metabolites by reverse-phase HPLC showed that all of the [3H]AA released during the first hour after TNF-alpha addition eluted as authentic AA, whereas in samples obtained at 24 h after addition of TNF-alpha, 25% of the [3H]AA had been converted into COX products as compared with only 9% in control cells. In keeping with these findings, TNF-alpha produced an increase of COX-2 expression, as judged from both RT-PCR studies and immunoblot of COX-2 protein, and a long-lasting activation of NF-kappaB. These data show that TNF-alpha produces in astrocytoma cells an early activation of both p38-MAP kinase and JNK, which is followed by the phosphorylation of cPLA2 and the release of AA. On the other hand, the activation of NF-kappaB may explain the induction of the expression of COX-2 and the delayed generation of prostanoids.

Secretory phospholipase A2 induces phospholipase Cgamma-1 activation and Ca2+ mobilization in the human astrocytoma cell line 1321N1 by a mechanism independent of its catalytic activity.

The effect of secretory phospholipase A2 (sPLA2) on intracellular Ca2+ signaling in human astrocytoma cells was studied. sPLA2 increased cytosolic [Ca2+] ([Ca2+]c) in both Ca2+-containing and Ca2+-free medium, thus suggesting Ca2+ release from intracellular stores. The activation by sPLA2 of arachidonate release via cytosolic PLA2 (cPLA2) was also independent of extracellular Ca2+. As sPLA2 requires Ca2+ for activity, these results indicate that both Ca2+ mobilization and cPLA2 activation induced by sPLA2 are unrelated to phospholipase activity but dependent on signaling mechanisms. The sPLA2-induced [Ca2+]c peak was sensitive to Bordetella pertussis toxin and inhibited by caffeine, suggesting its mediation by inositol 1,4,5-trisphosphate (IP3). sPLA2 induced tyrosine phosphorylation and membrane targeting of phospholipase Cgamma-1 (PLCgamma-1). Moreover, the Ca2+ peak was sensitive to protein tyrosine kinase inhibitors. sPLA2 activates two signaling pathways: one leading to the activation of the MAP kinase/cPLA2 cascade and another leading to PLCgamma activation and Ca2+ release.

4-trifluoromethyl derivatives of salicylate, triflusal and its main metabolite 2-hydroxy-4-trifluoromethylbenzoic acid, are potent inhibitors of nuclear factor kappaB activation.

1. The effect of two derivatives of salicylate, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) and 2-acetoxy-4-trifluoromethylbenzoic acid (triflusal), on the activation of NF-kappaB elicited by tumour necrosis factor-alpha (TNF-alpha) on human umbilical vein endothelial cells (HUVEC) was tested. 2. The expression of the mRNA of vascular cell adhesion molecule-1 (VCAM-1) was studied as an example of a gene the expression of which is regulated by NF-kappaB. To extend these findings to other systems, the induction of nitric oxide synthase in rat adherent peritoneal macrophages was studied. 3. Both HTB and triflusal were more potent than aspirin or salicylate as inhibitors of the nuclear translocation of NF-kappaB. The calculation of the IC50 values showed approximately 2 mM for HTB, 4 mM for aspirin and >4 mM for salicylate. 4. Comparison of the potency of these compounds on VCAM-1 mRNA expression showed complete inhibition by both triflusal and HTB at a concentration of 4 mM whereas aspirin and salicylate produced only 36-43% inhibition at the same concentration. 5. Inhibition of NF-kappaB activation was also observed in rat peritoneal macrophages stimulated via their receptors for the Fc portion of the antibody molecule with IgG/ovalbumin immune complexes. This was accompanied by a dose-dependent inhibition of nitrite production by the L-arginine pathway via iNOS. IC50 values for this effect were 1.13+/-0.12 mM (triflusal), 1.84+/-0.34 (HTB), 6.08+/-1.53 mM (aspirin) and 9.16+/-1.9 mM (salicylate). 6. These data indicate that the incorporation of a 4-trifluoromethyl group to the salicylate molecule strongly enhances its inhibitory effect on NF-kappaB activation, VCAM-1 mRNA expression and iNOS induction, irrespective of the presence of the acetyl moiety involved in the inhibition of cyclo-oxygenase.

Immunoglobulin E-mediated anaphylaxis activates nuclear factor kappaB in rat small intestine.

OBJECTIVE AND DESIGN: Since IgE-dependent reactions induce the inducible isoform of NO synthase, we postulated the involvement of the transcription factor NF-kappaB. MATERIALS: 72 Wistar rats were divided into 6 groups and used to study the hemorrhagic necrosis of the small intestine elicited by anaphylaxis. TREATMENT: Passive anaphylaxis was produced by i.p. sensitization with IgE anti-dinitrophenyl monoclonal antibody and i.v. challenge with the cognate antigen. METHODS: Competitive PCR was used to assay the expression of p50 subunit of NF-kappaB. kappaB-binding activity was assayed by electrophoretic mobility shift assay. RESULTS: The PCR assay showed a time-dependent increase of mRNA coding for the p50 subunit of NF-kappaB, which was maximal 1 h after challenge (40+/-3, versus 230+/-32 fM, mean +/- SEM) and decreased to prechallenge level at 4h. kappaB-binding activity was also increased. CONCLUSIONS: IgE-mediated reactions trigger a pathway for nuclear signaling that seems to be related to the intermediate/late response of the allergic reaction.

Immunoglobulin-E/dinitrophenyl complexes induce nitric oxide synthesis in rat peritoneal macrophages by a mechanism involving CD23 and NF-kappa B activation.

The production of nitric oxide (NO) by rat adherent peritoneal cells stimulated with preformed IgE/Dinitrophenyl-BSA (DNP-BSA) complexes and its dependence on the activation of the transcription factor NF-kappa B were studied. Stimulation with IgE/DNP-BSA complexes at equivalence induced both the production of NO and an increased expression of the inducible isoform of NO synthase (iNOS) protein. Both events were also elicited by a rabbit polyclonal F(ab')2 anti-CD23 cross-reacting with rat CD23, thus suggesting Fc epsilon RII/CD23 antigen as the IgE-binding structure involved in the triggering of the response and ruling out an interaction of the antibody via its Fc portion. Inhibition of redox-sensitive signaling mechanisms by the antioxidant pyrrolidine dithiocarbamate (PDTC) blocked NO production, iNOS expression, and NF-kappa B activation elicited by both IgE/DNP-BSA complexes and anti-CD23 F(ab')2, thus suggesting the involvement of NF-kappa B in the signaling pathway leading to the transcriptional activation of iNOS. These results show the existence in rat peritoneal macrophages of a signaling pathway triggered by CD23 engagement that promotes nuclear translocation of NF-kappa B and transcriptional activation of the inducible isoform of NO synthase.