Low bone mineral density, but not epidural steroid injection, is associated with fracture in postmenopausal women with low back pain.

BACKGROUND: Therapy with glucocorticoids often results in bone loss and glucocorticoid-induced osteoporosis. However, the relationship between epidural steroid injection (ESI), bone mineral density (BMD), and vertebral fracture remains to be determined. OBJECTIVE: To establish a relationship between ESI, BMD, and vertebral fracture in postmenopausal women with low back pain. STUDY DESIGN: This study was a retrospective, nonblinded, cross-sectional clinical study. SETTING: University-based pain management center. METHODS: We reviewed the medical records of postmenopausal women with low back pain who were treated with ESI. A total of 352 postmenopausal women were divided into 2 groups. Group 1 consisted of patients without fracture and Group 2 consisted of those with fractures. The results of BMD measurements, as well as any fragility fractures, the anatomical site involved, and the treatment administered, were also recorded. BMD was measured in the lumbar spine, femoral neck, and total femur after the treatment. RESULTS: Of the 352 patients, 218 (62%) had no fractures while 134 (38%) sustained a fracture. The age was significantly higher among patients who sustained fractures, and BMD at the lumbar spine, total femur, and femoral neck regions was significantly lower among patients who sustained fractures. In each region, the prevalence of osteoporosis was significantly higher in patients with fracture than in patients without fracture (all P < 0.05). Age, height, and weight were associated with low BMD. However, our study showed no consistent correlation between BMD and the mean number of ESIs, mean total dose of glucocorticoids, or mean duration of ESIs. LIMITATIONS: First, this study is limited by the fact that it was retrospective. Second, the number of cases receiving very frequent, high-dose glucocorticoid injections was very small. CONCLUSIONS: Older age and lower BMD were associated with osteoporotic fracture in postmenopausal women treated for low back pain with ESI. The ESIs were not associated with low BMD or fracture.

Intraoperative plasma lactate as an early indicator of major postoperative events in pediatric cardiac patients.

Hyperlactatemia and unmeasured anions (UMA) have been suggested to be useful predictors of outcomes after pediatric cardiac surgery in the ICU. However, if we detect high-risk patient in the operating room, we could practice early intervention to decrease mortality and morbidity. The purpose of this study was to determine whether the intraoperative lactate or UMA levels can predict adverse outcomes in pediatric cardiac patients with undergoing cardiopulmonary bypass (CPB). We studied 102 patients with congenital heart disease. Arterial blood samples were obtained after inducing anesthesia, 5 min after weaning from CPB and after chest closure. Major adverse events (MAEs) were defined as cardiac compression, re-sternotomy due to hemodynamic instability, extra-corporeal membrane oxygenator support, creatinine levels greater than 2 mg/dL, or death. Patients were divided into MAE group (8 patients, 7.8%) and non-MAE group. Six patients with MAEs died. Importantly, the lactate levels (mmol/L) at weaning from CPB (4.19 vs 2.1; MAE group vs non-MAE group), chest closure (5.76 vs 2.39; MAE group vs non-MAE group) and the intraoperative increases in lactate levels were significantly higher in the MAE group than in the non-MAE group. However, there was no significant difference in the UMA levels or their changes between the groups. The increase in the lactate level from CPB weaning to chest closure was the best predictor of MAEs (AUC: 0.810). In conclusion, the intraoperative plasma lactate levels were more closely associated with MAEs, and they are more useful for predicting the outcome of pediatric cardiac patients than the UMA levels.

Changes in bone mineral density in postmenopausal women treated with epidural steroid injections for lower back pain.

BACKGROUND: Therapy with corticosteroids often results in bone loss and corticosteroid-induced osteoporosis. In previous studies, bone mineral density (BMD) has been examined after administration of relatively high oral doses of corticosteroids. However, practitioners use comparatively lower doses of corticosteroids for epidural steroid injections (ESI). The interactions and relationships between BMD and ESI remain to be determined. OBJECTIVE: The aim of this study was to explore the relationship between BMD and ESI in postmenopausal women treated for lower back pain. STUDY DESIGN: This study was a retrospective evaluation. METHODS: We reviewed the medical records of postmenopausal women with lower back pain who were treated with or without ESI. BMD was measured before treatment and one year after treatment in the lumbar spine, femoral neck, and total femur. A total of 90 postmenopausal women were divided into 2 groups. Group 1 patients received medications without ESI; Group 2 patients received ESI more than 4 times, with a cumulative administered triamcinolone dose of > 120 mg. RESULTS: Decreased BMD was observed in patients treated with ESI. However, no significant difference was observed between or within the groups in terms of mean percentage change from baseline BMD. LIMITATIONS: First, this study is limited by the fact that it was retrospective. Second, our study did not consider the use of ESI with high-dose corticosteroids. Third, our study did not include any long-term assessments of the effects of ESI on BMD. CONCLUSIONS: These data suggest that ESI using triamcinolone (over 200 mg) for a period of one year will have a negative effect on BMD in postmenopausal women treated for lower back pain. However, ESI therapy using a maximum cumulative triamcinolone dose of 200 mg in one year would be a safe treatment method with no significant impact on BMD.

The dosages of corticosteroid in transforaminal epidural steroid injections for lumbar radicular pain due to a herniated disc.

BACKGROUND: Intervertebral disc herniations are the most common cause of lumbosacral radiculopathy, and transforaminal epidural steroid injection (TFESI) is an important tool in treating lumbosacral radiculopathy. But the ideal dose of corticosteroid in the epidural management of lumbosacral radiculopathy has yet to be determined. OBJECTIVE: The aim of this study was to determine the effective dose of steroids in TFESI for pain reduction in patients with lumbosacral radiculopathy. STUDY DESIGN: A randomized, double blind, controlled trial. SETTING: An interventional pain management practice center. METHODS: A total of 160 participants received 2 epidural injections of either 5 mg, 10 mg, 20 mg, or 40 mg of triamcinolone in one week intervals via TFESI. The degree of participant satisfaction and verbal numerical rating scale (VNRS) were assessed at pretreatment, one week, and 2 weeks after the first TFESI. RESULTS: The number of participants experiencing pain relief was significantly less than in other groups in the 5 mg triamcinolone group at one week after the first TFESI. There were no significant differences among the groups at one week after the second TFESI. VNRS decreased in the other groups except the triamcinolone 5 mg group at one week after the first TFESI. VNRS decreased in all groups at one week after the second TFESI. LIMITATIONS: The limitations include lack of placebo control group and lack of long-term follow-up. CONCLUSIONS: We recommend a minimal effective dose of corticosteroid (triamcinolone 10 mg) in TFESI for patients with lumbosacral radiculopathy.

Anti-inflammatory Activity of 1-docosanoyl Cafferate Isolated from Rhus verniciflua in LPS-stimulated BV2 Microglial Cells.

Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as protection of neuronal cells against excitotoxicity, the biological activity of 1-docosanoyl cafferate (DC) has not been examined. The objective of the present study was to evaluate the anti-inflammatory effects of DC, isolated from the stem bark of Rhus verniciflua, on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of cells with DC significantly attenuated LPS-induced NO production, and mRNA and protein expression of iNOS in a concentration-dependent manner. DC also significantly suppressed LPS-induced release of cytokines such as TNF-α and IL-1ß . Consistent with the decrease in cytokine release, DC dose-dependently and significantly attenuated LPS-induced mRNA expression of these cytokines. Furthermore, DC significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB induced by LPS stimulation was significantly suppressed with DC pretreatment. Taken together, the present study suggests that DC exerts its anti-inflammatory activity through the suppression of NF-kB translocation to the nucleus.

Propofol and aminophylline antagonize each other during the mobilization of intracellular calcium in human umbilical vein endothelial cells.

This study examined whether propofol and aminophylline affect the mobilization of intracellular calcium in human umbilical vein endothelial cells. Intracellular calcium was measured using laser scanning confocal microscopy. Cultured and serum-starved cells on round coverslips were incubated with propofol or aminophylline for 30 min, and then stimulated with lysophosphatidic acid, propofol and aminophylline. The results were expressed as relative fluorescence intensity and fold stimulation. Propofol decreased the concentration of intracellular calcium, whereas aminophylline caused increased mobilization of intracellular calcium in a concentration-dependent manner. Propofol suppressed the lysophosphatidic acid-induced mobilization of intracellular calcium in a concentration-dependent manner. Propofol further prevented the aminophylline-induced increase of intracellular calcium at clinically relevant concentrations. However, aminophylline reversed the inhibitory effect of propofol on the elevation of intracellular calcium by lysophosphatidic acid. Our results suggest that propofol and aminophylline antagonize each other on the mobilization of intracellular calcium in human umbilical vein endothelial cells at clinically relevant concentrations. Serious consideration should be given to how this interaction affects mobilization of intracellular calcium when these two drugs are used together.

A comparison of retrobulbar block, sub-Tenon block, and topical anesthesia during cataract surgery.

PURPOSE: This randomized, double-blinded, prospective study was performed to compare the intraoperative hemodynamic variables and the patient-reported outcomes, such as intra- and postoperative analgesia and patient satisfaction, of retrobulbar block, sub-Tenon block, and topical anesthesia during cataract surgery under monitored anesthesia care. METHODS: Eighty-one patients, ASA physical status I-III, undergoing elective cataract surgery under monitored anesthesia care, aged between 43 and 78 years, were randomly assigned to three groups: retrobulbar block (group R), sub-Tenon block (group S), or topical anesthesia (group T). Three minutes after the start of monitored anesthesia care with lidocaine-propofol-remifentanil mixture, an ophthalmologist performed regional anesthesia. Intraoperative hemodynamics, pain score, and patients' satisfaction with the anesthetic experiences were recorded by a study-blinded anesthesiologist. RESULTS: Mean arterial pressure and heart rate in group R were significantly higher than those in groups S and T during and just after the regional block (p<0.05). Group R required smaller dosage of patient controlled sedation and fewer supplemental bolus doses than groups S and T (p<0.05). On the other hand, group S showed the highest satisfaction scores among the three groups (p<0.05). CONCLUSIONS: Sub-Tenon block seems to be better than retrobulbar block and topical anesthesia in patient satisfaction though adequate analgesia was achieved after retrobulbar block during cataract surgery under monitored anesthesia care.

Alphaxalone, a neurosteroid anaesthetic, increases the activity of the glutamate transporter type 3 expressed in Xenopus oocytes.

Glutamate transporters may be important targets for anaesthetic action in the central nervous system. The authors investigated the effects of alphaxalone, an intravenous neurosteroid anaesthetic, on the activity of glutamate transporter type 3 (EAAT3). EAAT3 was expressed in Xenopus oocytes by injecting its mRNA. Two-electrode voltage clamping was used to record membrane currents before, during, and after applying L-glutamate (30 microM) in the presence or absence of alphaxalone. Responses were quantified by integrating current traces and are reported in microCoulombs (microC). Results are presented as means+/-S.E.M. L-Glutamate induced inward currents in EAAT3 expressing oocytes, and these currents were dose-dependently increased by alphaxalone. Alphaxalone at 0.01 to 3 microM significantly increased the inward currents. In addition, the treatment of oocytes with phorbol-12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator, significantly increased the transporter currents (1.0+/-0.2 to 1.4+/-0.2 microC; P<0.05). However, treatment with PMA plus alphaxalone did not increase responses further as compared with PMA or alphaxalone alone. Furthermore, pretreatment of oocytes with chelerythrine or staurosporine, two PKC inhibitors, did not affect basal transporter currents, but did significantly reduce alphaxalone-enhanced EAAT3 activity; whereas oocytes pretreated with wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, showed significant reductions in basal and alphaxalone-enhanced EAAT3 activities. The above results suggest that alphaxalone enhances EAAT3 activity and that PKC and PI3K are involved in this effect.

Synthetic wogonin derivatives suppress lipopolysaccharide-induced nitric oxide production and hydrogen peroxide-induced cytotoxicity.

Wogonin (5,7-dihydroxy-8-methoxyflavone) has been reported to exhibit a variety of biological properties including anti-inflammatory and neuroprotective functions. In this study, biological activities of diverse synthetic wogonin derivatives have been evaluated in two experimental cell culture models. Inhibitory activities of wogonin derivatives on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells and on hydrogen peroxide (H2O2)-induced neuronal cell death in SH-SY5Y human neuroblastoma were examined. Wogonin derivatives such as WS2 and WS3 showed more potent suppressive activities on LPS-induced NO production and H2O2-induced cytotoxicity than wogonin itself. In addition, thiol substitution played a minor role in enhancing the activities of the derivatives. These findings may contribute to the development of novel anti-inflammatory and neuroprotective agents derived from wogonin.

Modulation of suppressive activity of lipopolysaccharide-induced nitric oxide production by glycosidation of flavonoids.

Flavonoids have been demonstrated to exhibit a wide range of biological activities including anti-inflammatory and neuroprotective actions. Although a significant amount of flavonoids has been identified to be present as glycosides in medicinal plants, determinations of the biological activities of flavonoids were mainly carried out with aglycones of flavonoids. Therefore, the exact role of the glycosidation of flavonoid aglycones needs to be established. In an attempt to understand the possible role of glycosidation on the modulation of the biological activities of flavonoids, diverse glycosides of kaempferol, quercetin, and aromadendrin were examined in terms of their anti-inflammatory activity determined with the suppression of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells. The results indicated that glycosidation of aglycones attenuated the suppressive activity of aglycones on LPS-induced NO production. Although attenuated, some of glycosides, depending on the position and degree of glycosidation, maintained the inhibitory capability of LPS-induced NO production. These findings suggest that glycosidation of flavonoid aglycones should be considered as an important modulator of the biological activities of flavonoids.

Nitric oxide suppresses inducible nitric oxide synthase expression by inhibiting post-translational modification of IkappaB.

The expression of inducible nitric oxide synthase (iNOS) is a critical factor in both normal physiological functions and the pathogenesis of disease. This study was undertaken to determine the molecular mechanism by which nitric oxide (NO) exerts negative feedback regulation on iNOS gene expression. Isolated rat hepatocytes stimulated with cytokines exhibited a marked increase in NO production as well as iNOS mRNA and protein levels, which were significantly reduced by pretreatment of the NO donors S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and V-PYRRO/NO. This effect of SNAP was inhibited when NO was scavenged using red blood cells. Pretreatment with oxidized SNAP, 8-Br-cGMP, NO2-, or NO3- did not suppress the cytokine-induced NO production. Moreover, LPS/ IFN-gamma-stimulated RAW264.7 cells, which produce endogenous NO, expressed lower levels of iNOS, IL-1beta, IL-6 and TNF-alpha mRNAs, without changes in their mRNA half-lives, than those in the presence of the iNOS inhibitor NG-monomethyl-L-arginine. The iNOS gene transcription rate exhibited an 18-fold increase after cytokine stimulation, which was significantly inhibited by SNAP pretreatment. SNAP also blocked cytokine- induced increase in NF-kappaB activation, iNOS promoter activity, nuclear translocation of cytosolic NF-kappaB p65 subunit, and IkappaBalpha degradation, which correlated with its inhibitory effect on phosphorylation and ubiquitination of IkappaB. These data indicate that NO down-regulates iNOS gene expression and NO production by inhibiting the post-translational processes of IkappaBalpha thereby preventing NF-kappaB activation. These results identify a novel negative feedback mechanism whereby NO down-regulates iNOS gene expression.