Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.     

Intracisternal administration of COX inhibitors attenuates mechanical allodynia following compression of the trigeminal ganglion in rats

The purpose of the present study was to investigate the role of central cyclooxygenase (COX) pathways in the modulation of mechanical allodynia following compression of the left trigeminal ganglion. Experiments were carried out on male Sprague–Dawley rats mounted onto a stereotaxic frame under anesthesia. For compression, a 4% agar solution (10 μl) was injected into the trigeminal ganglion. In the control group, rats were sham operated without agar injections. Ipsilateral and contralateral air-puff thresholds significantly decreased following trigeminal ganglion compression. Mechanical allodynia was established within 3 days and lasted beyond postoperative day 30, returning to preoperative levels at approximately 55 days following compression. Intracisternal administration of indomethacin, a non-selective COX inhibitor, SC-560, a selective COX-1 inhibitor, or NS-398, a selective COX-2 inhibitor, significantly inhibited mechanical allodynia. The individual anti-allodynic effects of the three COX inhibitors persisted for 6 h and returned to pretreatment values within 24 h. Based on these results, the blockade of central COX pathways may comprise a potential new therapeutic tool for the treatment of trigeminal ganglion compression-induced nociception.     

塞来昔布超前镇痛在妇科腹腔镜手术患者的应用

【目的】观察塞来昔布超前镇痛对妇科腹腔镜手术患者的镇痛效果及其不良反应。【方法】将60例妇科腹腔镜手术治疗的患者随机分为观察组和对照组,观察组术前48h,24h给予塞来昔布200mg,对照组术前48h,24h给予口服安慰剂（复合维生素）。术后12h、24h、36h、48h、72h两组均予塞来昔布200mg,并用视觉模拟评分法（VAS）评价术后镇痛效果,同时调查患者的镇痛满意度（SD）与睡眠满意度（SS）,记录额外镇痛药物的援助情况和不良反应。两组患者于手术结束时及术后24h各取外周血2mL检测前列腺素E2（PGE2）的浓度。【结果】观察组术后2h、4h、8h、12h的VAS评分明显低于对照组（P〈0．05）。观察组SD与SS显著高于对照组（P〈0．01）,而观察组的额外镇痛药的使用和不良反应的发生都少于对照组。术后24h血清中PGE2浓度观察组也明显低于对照组（P〈0．01）。【结论】塞来昔布超前镇痛用于妇科腹腔镜手术,能有效缓解术后疼痛,改善睡眠状况,减少术后镇痛药物的使用且无明显不良反应。     

Expression of cyclooxygenase type 2 in lepromatous and tuberculoid leprosy lesions

BACKGROUND: Leprosy is an infectious disease with two polar forms, tuberculoid leprosy (TL) and lepromatous leprosy (LL), which are dominated by T-helper (Th) 1 and Th2 cells, respectively. High concentrations of prostaglandin E2 produced by the inducible enzyme cyclooxygenase type 2 (COX-2) in LL could inhibit Th1 cytokine production, contributing to T-cell anergy. OBJECTIVES: To compare the COX-2 expression in LL and TL. METHODS: Skin biopsies from 40 leprosy patients (LL, n = 20; TL, n = 20) were used to determine by immunohistochemistry and automated morphometry the percentage of COX-2 immunostained cells. RESULTS: Most COX-2-positive cells were macrophages; their percentages in the inflammatory infiltrate located in the papillary dermis, reticular dermis and periadnexally were significantly higher in LL than TL (P < 0.001 by Student's t-test). CONCLUSIONS: The high expression of COX-2 in LL may be related to high prostaglandin production contributing to T-cell anergy.     

大鼠直、结肠炎CLS的镇痛作用及COX2与GFAP在CNS表达的形态学观察

目的:研究化学性腰交感神经切除术(CLS)对直结肠慢性刺激性炎症和扩张性伤害性刺激(CRD)的中枢保护作用,为临床医学提供基础研究资料。方法:Wistar大鼠54只,随机分为6组,每组9只,按二因素析因实验设置实验组,另外设立实验对照组和空白对照组。利用直、结肠慢性刺激性炎性致痛模型,切除模型大鼠的腰交感神经后,运用机械扩张刺激观察大鼠行为变化。用Miampamba评分方法改良后疼痛四级评分标准评分,重复3次取均值记录结果。取间脑、脑桥、延髓、颈段(C5～8)、胸段(T3～6)、腰段(L1～3)、骶段(S2～4)脊髓连续切片后,延髓和脊髓用COX2,间脑、脑桥用胶质纤维酸性蛋白(GFAP)免疫组化染色,显微镜下观察相应核团,计数阳性细胞数。结果:LS无论作为预防性手术还是治疗性手术均能使中枢内GFAP和COX2表达阳性的细胞数下降(P<0.05)。NST,C5～8中间带和T3～6中间带外侧核不是直结肠慢性炎症刺激和CRD扩张性伤害刺激上传通路中的中继神经元(P>0.05)。一、二、三、四级反射各组比较直结肠扩张刺激阈值与手术顺序无关而与手术有关(P<0.05)。假手术不影响痛觉阈值(P>0.05),而手术后痛觉阈值明显上调(P<0.05)。结论:化学性腰交感神经切除术(CLS)在直结肠慢性炎症性刺激和CRD伤害刺激过程中能有效的保护中枢神经系统。腰交感     

Interference with the formation of the epididymal microenvironment-a new strategy for male contraception？

The cystic fibrosis transmembrane conductance regulator (CFTR) or the small conductance cAMP-activated chloride channel encoded by the CFTR gene has been shown to play an important role in the formation of the epididymal fluid microenvironment. Recent work in our laboratory has shown that this protein is also expressed by developing germ cells indicating a role of this protein in spermatogenesis. In view of the fact that the CFTR gene has a far reaching and widespread effect on human reproduction, understanding the role of CFTR in the male reproductive tissues and its intervention by pharmacological agents can open a new avenue of research into the development of novel male contraceptives. ( Asian J Androl 2000 ; 2 : 39 - 45 )     

Suppression of accelerated tumor growth in surgical wounds by celecoxib and indomethacin

BACKGROUND: Tumor growth is accelerated in surgical wounds. However, few experiments seeking to prevent such accelerated tumor growth have been performed. METHODS: We created surgical wounds in three syngeneic mice for the implantation of three murine cancer cell lines, SCC VII, CT-26, and B16F10. The tumor growth in the wound group was compared with that in non-wound-control mice. Celecoxib or indomethacin was administered to the mice that had tumor implanted into the surgical wound to observe the tumor-suppressive effect. RESULTS: The surgical wounds promoted tumor growth with different degrees, depending on the type of tumor. Such an accelerated tumor growth did not seem to be affected by cyclooxygenase-2 expression of tumors per se, but its mechanism needs to be explained by further studies. Celecoxib and indomethacin had a significant inhibitory effect on the tumor growth in the surgical wound. This suppressive effect is most obvious when celecoxib is administered daily from 1 day before surgical wounding and tumor implantation. CONCLUSION: Our results can justify that the preventive use of celecoxib in patients in whom local recurrence by tumor contamination is predicted.     

Overexpression of laminin-5 gamma2 chain and its prognostic significance in urothelial carcinoma of urinary bladder: association with expression of cyclooxygenase 2, epidermal growth factor receptor [corrected] and human epidermal growth factor receptor [corrected] 2

Laminin-5 (LN-5) and cyclooxygenase 2 (COX-2) play important roles in many kinds of cancers. Recently, it has been reported that epidermal growth factor receptor [corrected] (EGFR) and/or human epidermal growth factor receptor [corrected] 2 (HER2) expressions are associated with LN-5 and/or COX-2 expressions in a few carcinoma cell lines and human tumor tissue. LN-5, COX-2, EGFR, and HER2 expressions were examined immunohistochemically in 67 patients with urothelial carcinomas (UCs), and associations among these 4 biomarkers and clinicopathologic characteristics were investigated. Patients were classified into transurethral resection group and cystectomy group based on clinical end points, and prognostic significances of increased expressions were evaluated. Overexpression of LN-5, COX-2, EGFR, and HER2 was observed in 16 (23.9%), 34 (50.7%), 42 (62.7%), and 15 (22.4%) of 67 patients, respectively. LN-5 overexpression was associated high-grade (P = .002), invasive (pTa+1 versus pT2-4, P = .011), and nonpapillary (P = .027) UCs. Concerning EGFR and HER2, high-grade (EGFR, P = .0009; HER2, P = .003) and nonpapillary (EGFR, P = .016; HER2, P = .0002) UCs had a significantly higher overexpression rate. UCs penetrating basal membrane (pT1-4) showed significantly higher overexpression rates than pTa UCs on all biomarkers. In transurethral resection group, LN-5 overexpression could be proved as an independent prognostic parameter for intravesical recurrence (P = .007), whereas in cystectomy group, nodal involvement was an independent prognostic parameter for cause-specific survival (P = .025). The current study showed that the 4 biomarkers were associated with aggressive behaviors of UCs. Above all, LN-5 overexpression was considered to play an important role in intravesical recurrence of superficial UCs.