5-lipoxygenase (5LOX) is the key enzyme in the synthesis of leukotrienes from arachidonic acid. Hyperglucocorticoidemia, dexamethasone, and aging up-regulate 5LOX in the brain, including the cerebellum in vivo. We studied the mechanisms of dexamethasone-triggered 5LOX upregulation in primary cultures of rat cerebellar granule neurons (CGN). We measured 5LOX mRNA and protein contents, and the formation of cysteinyl leukotrienes (LTC 4 , LTD 4 , and LTE 4 7KHGH[DPHWKDVRQH0RUµM)-increased 5LOX mRNA and protein contents were already observed at 3 h of treatment, and they persisted for at least 24 h. Dexamethasone also LQFUHDVHG WKH FRQWHQW RI F\VWHLQ\O OHXNRWULHQHV DVVD\HG LQ WKH SUHVHQFH RI 0 FDOFLXP LRQRSKRUH $ DQG 0 DUDFKLGRQLF DFLG 7KH VWimulatory effect of dexamethasone on 5LOX expression was inhibited by the glucocorticoid receptor (GR) antagonist RU486 and by reducing the CGN content of GR receptor protein with a GR-specific antisense oligonucleotide. The 5LOX mRNA half-life was longer in dexamethasone than in vehicle-treated CGNs. Our results indicate that dexamethasone increases 5LOX expression in CGNs in a GR-dependent manner and that it also increases the stability of 5LOX mRNA. Further studies are warranted to elucidate the physiologic/pathologic significance of glucocorticoid-regulated expression of 5LOX in the central nervous system.-Lipoxygenase (5LOX) enzyme activity is crucial for the biosynthesis of inflammatory eicosanoids, leukotrienes (LTs) from arachidonic acid. 5LOX catalyzes the oxygenation of arachidonic acid, leading to formation of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and its subsequent dehydration into leukotriene A 4 (LTA 4 ). LTA 4 is the precursor for other LTs; that is, LTB 4 and the family of cysteinyl leukotrienes (cysLTs: LTC 4 , LTD 4 , and LTE 4 ) (1). In the brain, increased formation of cysLTs was found in response to seizures (2). Moreover, the brain also expresses a receptor specific for cysLTs, the cysteinyl leukotriene 2 receptor (3). An 5 increased expression of 5LOX during aging was associated with increased brain vulnerability to neurodegeneration (4). Thus, it has been suggested that inflammatory mechanisms, including the 5LOX pathway, might contribute to the pathophysiology of aging-associated brain disorders, such as Alzheimer's disease (5, 6).Recently, we have found that the content of 5LOX mRNA and protein in the central nervous system, including the cerebellum, increases after prolonged (10 days) treatment of rats with glucocorticoids, corticosterone, or dexamethasone (7). However, this rather unsuspected finding that anti-inflammatory hormones (i.e., glucocorticoids) whose secretion is increased in the elderly (8) also increase the expression of a proinflammatory enzyme (i.e., 5LOX) is not without precedent. Thus, it was reported recently that dexamethasone increases 5LOX mRNA and protein in human mast cells (9), and in human peripheral blood monocytes and the acute monocytic leukemia cell line, THP-1 (10). The exact mechanism of glucocorticoid-stimulated ...

Background: Pain while sitting is the primary complaint of many patients with lumbar spinal ailments, including those with discogenic low back pain and lumbar disc herniations. There has been little basic research on the different mechanical stresses that different sitting positions place on the spine. To demonstrate the effect of different sitting positions on lumbar intersegmental relationships. Methods: Twenty healthy male volunteer subjects were recruited. Lateral X-rays of the lower lumbar spine were taken in four positions: (I) relaxed lateral standing; (II) "standard" sitting position; (III) sitting on a "kneeling" chair; and (IV) unsupported sitting on a stool. Anterior and posterior disc height, disc space angulation, L1-S1 angulation and interspinous distance were measured. Results: The L1-S1 lordotic angle in the standing position (48.8°±14.7°) was found to be statistically significantly greater than the angle measured with any of the sitting positions: the kneeling chair (34.0°±17.7°); hardback chair (28.6°±14.3°); and the stool (16.6°±15.6°). Total average disc height (arithmetic sum of average disc heights L2-S1) in the lumbar spine varied with position: standing (40.5±7.75 mm); hardback chair (38.5±6.9 mm); kneeling chair (38.4±7.9 mm); stool (36.9±7.1 mm). The mean interspinous distance over all the lumbar levels was significantly greater in each of the three seated positions than in the standing position: standing 6.8±4.5 mm; 11.6°±7.5° for the kneeling chair; 12.9±5.8 mm for the hardback chair; 16.9±7.0 mm for the stool. Conclusions: If segmental flexion and segmental loading are the important biomechanical correlates of pain on sitting, such patients should be most comfortable in a kneeling chair, which most closely approximates the standing position. These basic findings will allow better assessment of different seating positions from an ergonomic perspective, and hopefully lead to improvements in chair design.

Background: Pain while sitting is the primary complaint of many patients with lumbar spinal ailments, including those with discogenic low back pain and lumbar disc herniations. There has been little basic research on the different mechanical stresses that different sitting positions place on the spine. To demonstrate the effect of different sitting positions on lumbar intersegmental relationships.Methods: Twenty healthy male volunteer subjects were recruited. Lateral X-rays of the lower lumbar spine were taken in four positions: (I) relaxed lateral standing; (II) "standard" sitting position; (III) sitting on a "kneeling" chair; and (IV) unsupported sitting on a stool. Anterior and posterior disc height, disc space angulation, L1-S1 angulation and interspinous distance were measured.Results: The L1-S1 lordotic angle in the standing position (48.8°±14.7°) was found to be statistically significantly greater than the angle measured with any of the sitting positions: the kneeling chair (34.0°±17.7°); hard-back chair (28.6°±14.3°); and the stool (16.6°±15.6°). Total average disc height (arithmetic sum of average disc heights L2-S1) in the lumbar spine varied with position: standing (40.5±7.75 mm); hard-back chair (38.5±6.9 mm); kneeling chair (38.4±7.9 mm); stool (36.9±7.1 mm). The mean interspinous distance over all the lumbar levels was significantly greater in each of the three seated positions than in the standing position: standing 6.8±4.5 mm; 11.6°±7.5° for the kneeling chair; 12.9±5.8 mm for the hard-back chair; 16.9±7.0 mm for the stool.Conclusions: If segmental flexion and segmental loading are the important biomechanical correlates of pain on sitting, such patients should be most comfortable in a kneeling chair, which most closely approximates the standing position. These basic findings will allow better assessment of different seating positions from an ergonomic perspective, and hopefully lead to improvements in chair design.