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Background: The antinociceptive effect of an aqueous extract from the leaves of Toona sinensis (TS, [A. Juss., M. Roem.]) was studied using the writhing test in mice. Methods: Different extraction fractions from TS leaf extracts (TSL1 to TSL5) were administered orally 1 h before intraperitoneal injection of acetic acid. Results: After treatment with TSL1, TSL2, TSL3, TSL4, and TSL5 at a dose of 1 g/kg, the respective writhing responses were 39.9% (P < 0.001), 19.9% (P < 0.05), 11.7% (P = 0.052), 8.1% (P = 0.188), and 11.4% (P = 0.057) lower than the control group. Mice treated with TSL1 at 1 g/kg (39.9%, P < 0.001), 0.3 g/kg (38.0%, P < 0.001), 0.1 g/kg (46.9%, P < 0.001), and 0.03 g/kg (31.1%, P < 0.001) had significantly lower writhing responses compared with control mice. A time-course experiment was performed, which involved oral administration of TSL1 (0.1 g/kg) at 0, 0.5, 1, 2, and 6 h before acetic acid intraperitoneal injection. The most effective dose of TSL1 was 0.1 g/kg orally, with the effect beginning 30 min before treatment and persisting until 6 h. Conclusions: This study showed that TS has anti-visceral pain properties comparable with those of rofecoxib (a cyclooxygenase-2 inhibitor) and diclofenac, which suggests promise for the treatment of intractable visceral pain in humans. [ABSTRACT FROM AUTHOR]

Background: The Oswestry Disability Index (ODI) is widely used for patients with back pain. However, few studies have examined its psychometric properties using modern measurement theory. The purpose of this study was to investigate the psychometric properties of the ODI in patients with back pain using Rasch analysis. Methods: A total of 408 patients with back pain participated in this cross-sectional study. Patients were recruited from the orthopedic, neurosurgery, rehabilitation departments and pain clinic of two hospitals. Rasch analysis was used to examine the Chinese version of ODI 2.1 for unidimensionality, item difficulty, category function, differential item functioning, and test information. Results: The fit statistics showed 10 items of the ODI fitted the model's expectation as a unidimensional scale. The ODI measured the different levels of functional limitation without skewing toward the lower or higher levels of disability. No significant ceiling and floor effects and gaps among the items were found. The reliability was high and the test information curve demonstrated precise dysfunction estimation. Conclusions: Our results showed that the ODI is a unidimensional questionnaire with high reliability. The ODI can precisely estimate the level of dysfunction, and the item difficulty of the ODI matches the person ability. For clinical application, using logits scores could precisely represent the disability level, and using the item difficulty could help clinicians design progressive programs for patients with back pain. [ABSTRACT FROM AUTHOR]

During disease progression to AIDS, HIV-1 infected individuals become increasingly immunosuppressed and susceptible to opportunistic infections. It has also been demonstrated that multiple subsets of dendritic cells (DC), including DC-SIGN(+) cells, become significantly depleted in the blood and lymphoid tissues of AIDS patients, which may contribute to the failure in initiating effective host immune responses. The mechanism for DC depletion, however, is unclear. It is also known that vast quantities of viral envelope protein gp120 are shed from maturing HIV-1 virions and form circulating immune complexes in the serum of HIV-1-infected individuals, but the pathological role of gp120 in HIV-1 pathogenesis remains elusive. Here we describe a previously unrecognized mechanism of DC death in chronic HIV-1 infection, in which ligation of DC-SIGN by gp120 sensitizes DC to undergo accelerated apoptosis in response to a variety of activation stimuli. The cultured monocyte-derived DC and also freshly-isolated DC-SIGN(+) blood DC that were exposed to either cross-linked recombinant gp120 or immune-complex gp120 in HIV(+) serum underwent considerable apoptosis after CD40 ligation or exposure to bacterial lipopolysaccharide (LPS) or pro-inflammatory cytokines such as TNFα and IL-1β. Furthermore, circulating DC-SIGN(+) DC that were isolated directly from HIV-1(+) individuals had actually been pre-sensitized by serum gp120 for activation-induced exorbitant apoptosis. In all cases the DC apoptosis was substantially inhibited by DC-SIGN blockade. Finally, we showed that accelerated DC apoptosis was a direct consequence of excessive activation of the proapoptotic molecule ASK-1 and transfection of siRNA against ASK-1 significantly prevented the activation-induced excessive DC death. Our study discloses a previously unknown mechanism of immune modulation by envelope protein gp120, provides new insights into HIV immunopathogenesis, and suggests potential therapeutic approaches to prevent DC depletion in chronic HIV infection. [ABSTRACT FROM AUTHOR]

Introduction: Increased endothelin-1 (ET-1) production and diminished nitric oxide synthase (NOS) bioavailability has been observed in aneurysmal subarachnoid hemorrhage (SAH). The authors previously found that 6-mercaptopurine (6-mp) is effective in preventing and reversing arterial narrowing in a rodent SAH model. This present study is of interest to examine the effect of 6-mp on ET-1/endothelial nitric oxide synthase (eNOS) in this animal model. Methods: A rodent double hemorrhage SAH model was employed. Animals were randomly assigned to six groups (sham, SAH only, vehicle, 0.5, 1.0 and 2 mg kg day 6-mp treatment). Monoclonal CD45 immunostaining was utilized to evaluate monocytes and microglia. The level of pro-inflammatory cytokines, such as IL-1, IL-6 and TNF-α(RT-PCR), and ET-1 (ELISA) was measured. The basilar arteries (BAs) were harvested and sliced, and their cross-sectional areas were determined. Radiolabeled NOS assay kit was applied to detect eNOS. Results: Morphologically, convolution of internal elastic lamina, endothelial cells distortion, and necrotic smooth muscle were prevalently present in the basilar artery of SAH groups, which was absent in the 1 and 2 mg kg day 6-mp plus SAH group or the healthy controls. Significant vasospasm was noted in the vehicle group (lumen patency, 54.6%, p ≤ 0.01 compared with the sham group), but it was less prominent in the 2 mg kg day 6-mp treatment group (lumen patency, 87.6%, p < 0.05). In addition, administration with 2 mg kg day 6-mp reduced cytokine levels by 11%, 47%, and 34% for IL-1, IL-6, and TNF-α, respectively, and increased ET-1 levels were found in all the animals subject to SAH (SAH only, SAH plus vehicle, SAH plus 0.5 and 1.0 mg kg day 6-mp) except in the 2 mg kg day 6-mp SAH group, when compared with the healthy controls (no SAH). Meanwhile, treatment with 6-mp did not induce the levels of expressed eNOS in BAs in the 6-mp groups (0.5, 1.0, and 2 mg kg day 6-mp plus SAH) when compared with that in the SAH groups ( p > 0.1). Conclusion: In summary, treatment with 6-mp decreased the release of pro-inflammatory cytokines and diminished experimental vasospasm. This study offered first evidence that 6-mp dose-dependently reduces the level of ET-1 in a NO-independent mechanism, which corresponds to its antivasospastic effect in the condition of chronic vasospasm. [ABSTRACT FROM AUTHOR]

Purpose: Although instrumented posterior lumbar interbody fusion (PLIF) has been becoming a popular and effective method for treating degenerative lumbar scoliosis, the clinical outcome is rarely reported. We retrospectively evaluated the clinical and radiographic outcomes in patients with degenerative lumbar scoliosis after instrumented PLIF. Materials and methods: A total of 58 patient's clinical characteristics had been reviewed retrospectively including clinical presentations, preoperative medical comorbidities, intraoperative status, and postoperative status. Oswestry disability index (ODI), visual analog scale (VAS), and patient satisfaction were evaluated before surgery and last follow-up period. The relationship between the difference of radiographic parameter and functional outcome was evaluated. Results: Functional outcomes including ODI scores and VAS were significantly improved at the last visit. The ODI was 28.1 ± 8.0 before surgery and 12.2 ± 8.8 at the last visit. VAS was 7.4 ± 2.0 before surgery and 2.4 ± 2.0 at the last visit. Patient satisfaction was 72% at the last visit. ODI was significantly related to postoperative radiographic parameters including Cobb's angle ( p < 0.001), L4 inclination ( p = 0.011), coronal balance ( p = 0.007), lateral vertebral translation ( p < 0.001), Nash-Moe grade ( p = 0.033), Nash-Moe degree ( p = 0.025), and sagittal balance ( p = 0.041) Using multiple regression analysis, ODI was significantly related to female gender, number of levels fixed, coronal balance, lateral vertebral translation, and Nash-Moe degree. The was no significant correlation between postoperative radiographic parameters and pain (VAS). Only lateral vertebral translation demonstrated a significant correlation in multiple regression analysis. Conclusions: Based on the VAS and ODI instrument, our studies demonstrated that instrumented PLIF for adult degenerative lumbar scoliosis can achieve a high rate of patient satisfaction and improvement in radiographic and clinical outcomes at a minimum of 2 years of follow-up. [ABSTRACT FROM AUTHOR]

Induced endothelin-1 (ET-1) production and decreased nitric oxide synthase (NOS) bioavailability have been found in aneurysmal subarachnoid hemorrhage (SAH). Atorvastatin is recognized to have pleiotropic effects including increasing NOS bioavailability as well as reducing inflammation and oxidative damage other than reducing dyslipidemia. This study is of interest to examine the effect of atorvastatin on ET-1/endothelial nitric oxide synthase (eNOS) in experimental SAH. A rodent double-hemorrhage SAH model was employed. Animals were randomly assigned as sham-operated, SAH, vehicle plus SAH, 5 mg/day atorvastatin treatment plus SAH and 5 mg/day atorvastatin precondition plus SAH groups. Administration with atorvastatin (5 mg/day) was initiated 1 week before (precondition) and 24 hr later (treatment). Cerebrospinal fluid samples were collected at 72 hr after second SAH. ET-1 (ELISA) was measured. The basilar arteries (BAs) were harvested and sliced, and their cross-sectional areas were measured. Radiolabeled NOS assay kit was used to detect eNOS. Morphologically, convoluted internal elastic lamina, distorted endothelial cells and myonecrosis of the smooth muscle were predominantly observed in the BA of SAH and vehicle-treated SAH groups, which was not detected in the atorvastatin-preconditioned SAH group or the healthy controls. Significant vasospasm was noted in the vehicle group (lumen potency 64.5%, compared with the sham group, p ≤ 0.01) and less prominent in the atorvastatin treatment group (lumen potency, 76.6%, p < 0.05). In addition, increased ET-1 levels were found in all the animals subject to SAH (SAH only, SAH plus vehicle and SAH plus atorvastatin reversal) except in the atorvastatin precognition group when compared with the healthy controls (no SAH). Likewise, the levels of expressed NOS in BAs is induced in the atorvastatin groups (both atorvastatin treatment and precondition) when compared with that in the SAH group ( p < 0.01). This study offers first evidence that atorvastatin in the preconditioning status reduces the level of ET-1, which corresponds to its antivasospastic effect in the condition of chronic vasospasm. Although there is increased expression of NOS in both atorvastatin precondition and reversal groups, BA’s lumen potency is significantly increased in the atorvastatin precondition group when compared with the SAH group ( p < 0.01). [ABSTRACT FROM AUTHOR]

The endemic species of Antrodia camphorate (AC) is a promising chemotherapeutic drug for cancer. We found that the ethanol extract from wild fruiting bodies of Antrodia camphorata (EEAC) could induce HL 60 cells apoptosis via histone hypoacetylation, up-regulation of histone deacetyltransferase 1 (HDAC 1), and down-regulation of histone acetyltransferase activities including GCN 5, CBP and PCAF in dose-dependent manner. In combination with histone deacetylase inhibitor, trichostatin A (TSA), did not block EEAC-induced apoptosis. Interestingly, combined treatment (100 nM of TSA and 100 μg/ml EEAC) caused synergistic inhibition of cell growth and increase of apoptotic induction. EEAC could effectively increase the cytotoxic sensitivity of TSA through the up-regulation of DR5 and NFκB activation. In this present study, bioassay-guided fractionation of EEAC led to a major active compound, zhankuic acid A, as the bioactive marker. Moreover, our findings may represent an experimental basis for developing EEAC as a potential chemotherapeutic adjuvant. [ABSTRACT FROM AUTHOR]

Summary A very rare case of a giant nondural-based cauda equina meningioma with multiple cysts was presented. Spinal meningioma most commonly occurs in the thoracic or cervical region and typically adheres to the dura. Only six cases of nondural-based meningioma have been reported in English literature. All occurred in the cauda equina region. These patients were predominantly female and younger than those with typical intraspinal meningioma. [ABSTRACT FROM AUTHOR]