RESUMEN
Managing major thoracic trauma begins with identifying and anticipating injuries associated with the mechanism of injury. The key aims are to reduce early mortality and the impact of associated complications to expedite recovery and restore the patient to their pre-injury state. While imaging is imperative to identify the extent of thoracic trauma, some pathology may require immediate treatment. The majority can be managed with adequate pleural drainage, but respiratory failure and poor gas exchange may require either non-invasive or invasive ventilation. Ventilation strategies to protect from complications such as barotrauma, volutrauma and ventilator-induced lung injury are important to consider. The management of pain is vital in reducing respiratory complications. A multimodal strategy using local, regional and systemic analgesia may mitigate respiratory side effects of opioid use. With optimal pain management, physiotherapy can be fully utilised to reduce respiratory complications and enhance early recovery. Thoracic surgeons should be consulted early for consideration of surgical management of specific injuries. With a greater understanding of the mechanisms of injury and the appropriate use of available resources, favourable outcomes can be reached in this cohort of patients. Overall, a multidisciplinary and holistic approach results in the best patient outcomes.
Asunto(s)
Analgesia , Traumatismos Torácicos , Humanos , Traumatismos Torácicos/terapia , Traumatismos Torácicos/complicaciones , Dolor/etiología , Manejo del Dolor/métodos , Analgesia/métodos , PulmónRESUMEN
Postmenopausal loss of 17 beta-estradiol (E2) in women is associated with decreased bone mineral density and increased susceptibility to osteoporotic bone fracture. These changes in bone status are assumed to be due to circulating levels of the hormone; therapeutic replacement of E2 can alleviate the bone disease. However, recent reports have shown that human osteoblastic (OB) cells are able to synthesize estrogens locally, via expression of the enzyme aromatase. In this study, we have characterized the expression and activity of aromatase and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) in rat OB cell lines. Aromatase activity in ROS 17/2.8, ROS 25/1, and UMR 106 cells was similar to that shown in human OB cells, with the highest levels of activity observed in the more differentiated ROS 17/2.8 cells (Vmax = 45 pmol/h/mg of protein). The rat OB cells also showed 17 beta-HSD activity, with the predominant metabolism in all three cell lines being estrone (E1) to E2. As with aromatase, the highest activity was observed in ROS 17/2.8 cells (Vmax = 800 pmol/h/mg of protein). Northern analyses indicated the variable presence of transcripts corresponding to the type 1, 2, 3, and 4 isoforms of 17 beta-HSD. Further analysis of androstenedione metabolism indicated that the net effect of aromatase and 17 beta-HSD activity varied with cell type and culture treatment. All three OB cell lines were able to synthesize E1, E2, and testosterone from androstenedione, although activity varied between OB cell types. Regulatory effects were observed with 1,25-dihydroxyvitamin D3 (positive) and dexamethasone (negative). These data suggest that local synthesis of sex hormones is an important function of OB cells and may play a key role in the modulation of bone turnover independent of circulating hormone concentrations.
Asunto(s)
17-Hidroxiesteroide Deshidrogenasas/biosíntesis , Aromatasa/biosíntesis , Isoenzimas/biosíntesis , Osteoblastos/enzimología , 17-Hidroxiesteroide Deshidrogenasas/genética , Androstenodiona/metabolismo , Animales , Aromatasa/genética , Northern Blotting , Diferenciación Celular/genética , Estradiol/biosíntesis , Estrona/biosíntesis , Isoenzimas/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Ratas , Testosterona/biosíntesis , Células Tumorales CultivadasRESUMEN
Studies in vitro and in vivo have shown that corticosteroids play an important role in bone physiology and pathophysiology. It is now established that corticosteroid hormone action is regulated, in part, at the pre-receptor level through the expression of isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), which are responsible for the interconversion of hormonally active cortisol to cortisone. In this report we demonstrate 11beta-HSD activity in human osteoblast (OB) cells. Osteosarcoma-derived OB cell lines TE-85, MG-63 and SaOS-2 and fibrosarcoma Hs913T cells express the type 2 isoform of 11beta-HSD, as determined by reverse transcription polymerase chain reaction (RT-PCR) and specific enzyme assays. Enzyme activity was shown to be strictly NAD dependent with a Km of approximately 71 nM; 11beta-HSD type 1 mRNA expression and enzyme activity were not detected. All four cell lines expressed mRNA for the glucocorticoid receptor (GR) and mineralocorticoid receptor, but specific binding was only detectable with radiolabelled dexamethasone (Kd=10 nM) and not aldosterone. MG-63 cells had two to three times more GR than the other OB cells, which correlated with the higher levels of 11beta-HSD 2 activity in these cells. In contrast to the osteosarcoma cell studies, RT-PCR analysis of primary cultures of human OB cells revealed the presence of mRNA for 11beta-HSD 1 as well as 11beta-HSD 2. However, enzyme activity in these cells remained predominantly oxidative, i.e. inactivation of cortisol to cortisone (147 pmol/h per mg protein at 500 nM cortisol) was greater than cortisone to cortisol (10.3 pmol/h per mg protein at 250 nM cortisone). Data from normal human OB and osteosarcoma cells demonstrate the presence of an endogenous mechanism for inactivation of glucocorticoids in OB cells. We postulate that expression of the type 1 and type 2 isoforms of 11beta-HSD in human bone plays an important role in normal bone homeostasis, and may be implicated in the pathogenesis of steroid-induced osteoporosis.
Asunto(s)
Cortisona/metabolismo , Hidrocortisona/metabolismo , Hidroxiesteroide Deshidrogenasas/metabolismo , Osteosarcoma/metabolismo , Receptores de Esteroides/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasas , Actinas/genética , Aldosterona/metabolismo , Northern Blotting , Dexametasona/metabolismo , Glucocorticoides/metabolismo , Humanos , Hidroxiesteroide Deshidrogenasas/genética , Isoenzimas/metabolismo , Osteosarcoma/enzimología , Unión Proteica , ARN Mensajero/análisis , Receptores de Esteroides/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
Pharmacokinetics of ceftriaxone after a single dose of 50 or 75 mg/kg were determined in 30 pediatric patients with bacterial meningitis. Data for doses of 50 and 75 mg/kg, respectively, were as follows (mean +/- standard deviation): maximum plasma concentrations, 230 +/- 64 and 295 +/- 76 mug/ml; elimination rate constant, 0.14 +/- 0.06 and 0.14 +/- 0.04 h(-1); harmonic elimination half-life, 5.8 +/- 2.8 and 5.4 +/- 2.1 h; plasma clearance, 51 +/- 24 and 55 +/- 18 ml/h per kg; volume of distribution, 382 +/- 129 and 387 +/- 56 ml/kg; mean concentration in cerebrospinal fluid 1 to 6 h after infusion, 5.4 and 6.4 mug/ml. A dosage schedule of 50 mg/kg every 12 h for bacterial meningitis caused by susceptible organisms is suggested for pediatric patients over 7 days of age.
Asunto(s)
Antibacterianos/metabolismo , Cefotaxima/análogos & derivados , Meningitis/metabolismo , Cefotaxima/líquido cefalorraquídeo , Cefotaxima/metabolismo , Cefotaxima/uso terapéutico , Ceftriaxona , Preescolar , Humanos , Lactante , Recién Nacido , Cinética , Meningitis/tratamiento farmacológicoRESUMEN
11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) acts as a pre-receptor signaling mechanism for corticosteroids by regulating the access of active glucocorticoids to both glucocorticoid (GR) and mineralocorticoid receptors (MR). To examine the relationship between endogenous glucocorticoid metabolism and osteoblast function, we have characterized the expression of 11 beta-HSD isozymes in rat osteosarcoma cells. Analysis of mRNA from ROS 25/1, UMR 106 and ROS 17/2.8 cells revealed transcripts for both 11 beta-HSD type 1 (11 beta-HSD1) and type 2 (11 beta-HSD2) in all three cell lines. However, enzyme activity studies showed only high affinity dehydrogenase activity (inactivation of corticosterone (B) to 11-dehydrocorticosterone (A)), characteristic of 11 beta-HSD2; conversion of B to A was higher in ROS 25/1> UMR 106 cells>ROS 17/2.8. Although all three cell lines had similar numbers of GR (50,000/cell), glucocorticoid modulation of alkaline phosphatase activity and cell proliferation was only detectable in ROS 17/2.8 cells. Further studies showed that 11 beta-HSD2 activity in each of the cells was potently stimulated by both A and B, but not by synthetic dexamethasone. This effect was blocked by the 11 beta-HSD inhibitor, 18 beta-glycyrrhetinic acid (but not by GR or MR antagonists) suggesting direct, allosteric regulation of 11 beta-HSD2 activity. These data indicate that in osteosarcoma cells 11 beta-HSD2 plays a key role in controlling GR-mediated responses; cells with relatively high levels of 11 beta-HSD2 activity were insensitive to glucocorticoids, whilst cells with low levels showed functional responses to both dexamethasone and B. In addition to the established effects of 11 beta-HSD2 in protecting MR in the kidney and colon, our data suggest that 11 beta-HSD2 in bone represents an important pre-receptor mechanism in determining ligand availability to GR.
Asunto(s)
Glucocorticoides/farmacología , Hidroxiesteroide Deshidrogenasas/metabolismo , Osteoblastos/enzimología , Receptores de Glucocorticoides/fisiología , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1 , Animales , Secuencia de Bases , Cartilla de ADN , Hidroxiesteroide Deshidrogenasas/genética , Ratas , Receptores de Glucocorticoides/metabolismo , Células Tumorales CultivadasRESUMEN
The Cane River and Rio Minho watersheds are currently undergoing intense environmental degradation, mainly due to uncontrolled burning and deforestation. The classic, diagnostically recognizable effects upon land surface climatology, hydrological regime, and channel geomorphology are increasingly evident. Comparison with some watersheds of similar macroclimate and geomorphology in Haiti and India suggest that those in Jamaica, while fairly advanced, are not yet so seriously degraded as in those countries, but will soon be irreversibly modofied unless urgent remedial action is taken.(AU)