COMBINATION OF RADIATION THERAPY AND FIROCOXIB FOR THE TREATMENT OF CANINE NASAL CARCINOMA

Carcinomas represent two‐thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase‐isoform‐2 (COX‐2) is expressed in 71–95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX‐2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX‐2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality‐of‐life questionnaire. Twenty‐four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression‐free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression‐free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression‐free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas.     

Characterization of an intravenous lipopolysaccharide inflammation model in calves with respect to the acute-phase response

Our objective was to develop a lipopolysaccharide (LPS) inflammation model in calves to evaluate the acute-phase response with respect to the release of pro-inflammatory cytokines and acute-phase proteins, fever development and sickness behaviour. Fourteen 4-week-old male Holstein Friesian calves were included and randomly assigned to a negative control group (n = 3) and an LPS-challenged group (n = 11). The latter received an intravenous bolus injection of 0.5 μg of LPS/kg body weight. Blood collection and clinical scoring were performed at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 28, 32, 48, 54 and 72 h post LPS administration (p.a.). In the LPS group, the following clinical signs were observed successively: tachypnoea (on average 18 min p.a.), decubitus (29 min p.a.), general depression (1.75 h p.a.), fever (5 h p.a.) and tachycardia (5 h p.a.). Subsequent to the recovery from respiratory distress, general depression was prominent, which deteriorated when fever increased. One animal did not survive LPS administration, whereas the other animals recovered on average within 6.1 h p.a. Moreover, the challenge significantly increased plasma concentrations of tumour necrosis factor-α, interleukin 6, serum amyloid A and haptoglobin, with peaking levels at 1, 3.5, 24 and 18 h p.a., respectively. The present LPS model was practical and reproducible, caused obvious clinical signs related to endotoxemia and a marked change in the studied inflammatory mediators, making it a suitable model to study the immunomodulatory properties of drugs in future research.     

容忍最小收益下带干扰的双C O X风险模型

Lundberg-Cramer经典保险风险模型及其推广后的许多风险模型在研究破产概率时都假定破产时刻为盈余过程首次取负值的时刻.但在保险实务中,当盈余低于容忍最小收益时,保险公司就很难再经营下去或需要调整经营策略.在定义盈余低于容忍最小收益时的时刻为破产时刻的基础上,建立一个带干扰且保费随机收取的双COX风险模型,利用鞅论方法,研究其最终破产概率的性质及Lundberg型不等式.     

补中益气丸对糖尿病大鼠胃组织MUC1、COX、NOS表达变化及相互作用

观察补中益气丸对糖尿病大鼠胃组织MuC1、COX-1、COX-2、cNOS、iNOS不同病程表达变化及其相互作用的影响、大鼠随机分为正常组。模型组和中药组,采用STZ腹腔注射结合乙醇灌胃的方法建立糖尿病大鼠胃黏膜损伤模型．检测胃组织NO、PGE2、6-ketoPC-F1d、MuCl、COX-1、cOX2、cNOS和iNOs随病程的表达变化及其相互作用。结果显示,糖尿病大鼠出现胃黏膜损伤和胃肠功能紊乱,胃组织MUC1、COX2、iNOS发生显著变化．MUC1随病程进展逐渐降低,iNOs和COX-2表现为早期活性降低,晚期活性升高,PGE2、6-keto—PGF1d和NO随病程显著升高,相关分析发现．COX1与cNOS呈显著正相关,与iNOS呈著负相关。补中益气丸能调节MUC1、COX-2、iNOS的表达及其相互作用,阻止胃黏膜损伤。结果表明,STZ腹腔注射结合乙醇灌胃的方法可成功诱导糖尿病大鼠胃黏膜损伤模型,iNOS与COX2可能为相互协作和相互介导的关系,在糖尿病胃黏膜损伤方面起重要作用,补中益气丸通过升高MUC1、降低iNOS和COX-2的表达及其相互作用,阻止胃黏膜损伤和糖尿病的发展。     

Biologically active components of a Papua New Guinea analgesic and anti-inflammatory lichen preparation

A traditional preparation of Parmotrema saccatilobum (Taylor) Hale (Family: Parmeliaceae) is being considered for inclusion into the PNG national drug formulary by the Ministry of Health Taskforce on Traditional Medicines. The lichen preparation is traditionally used in the Milne Bay province of Papua New Guinea for analgesic and anti-inflammatory activities. A hexane extract of P. saccatilobum yielded the principle components atranorin and chloroatranorin. Atranorin and chloroatranorin were tested in a COX-1 and -2 enzyme inhibition assay, which showed that atranorin inhibited COX-1 in a dose dependent manner and suggests partial inhibition by atranorin and chloroatranorin of COX-2 and COX-1, respectively.     

Treatment of oral squamous cell carcinoma in a horse by surgical debulking followed by metronomic chemotherapy

A 19‐year‐old Quarter Horse gelding presented with a 6‐week history of hypersalivation, halitosis and dysmasesis. Oral examination revealed retention of food and saliva and the presence of a raised, nodular, 6 × 7 cm, ulcerated mass on the dorsal surface of the tongue base. The mass was confirmed histologically as squamous cell carcinoma. Complete resection of the mass was not possible and surgical laser debulking was followed 15 days later by chemotherapy with a combination of meloxicam and cyclophosphamide in metronomic regimen. After one week, there was a significant improvement in clinical signs and food consumption returned to normal. Therapy was well tolerated with no alteration in haematological or urinalysis parameters. After 5 months of excellent life quality, the horse showed progressive difficulties in mastication and swallowing. Endoscopic examination showed extension of the tumour to all the aboral aspect of the tongue and, with the owner's consent, the patient was subjected to euthanasia. This is believed to be the first report on the combined use of meloxicam and cyclophosphamide in a metronomic fashion for management of an oral squamous cell carcinoma in a horse. Since metronomic therapy is less expensive than conventional chemotherapy, easily administrable and well tolerated, it should be considered as a possible treatment option for nonresectable equine malignant tumours.     

民猪细胞色素C氧化酶Ⅰ基因的克隆、多态性检测及冷诱导研究

采用克隆测序和PCR- SSCP方法对民猪COX Ⅰ基因序列及多态性进行了检测与分析,采用实时荧光定量PCR法对同一饲养水平下经冷诱导处理的民猪和长白猪肌肉、肝脏组织中COX Ⅰ基因的表达变化进行分析.结果表明:民猪的COX Ⅰ基因序列与其他猪种相比,存在18个核苷酸突变,导致5个氨基酸发生变化;C260T、G275A和C1253T位点民猪以B等位基因占优势,大白猪、长白猪、北京黑猪、野猪则是A等位基因占优势;冷诱导后低温组民猪COX Ⅰ基因的表达量与常温组民猪和低温组长白猪相比,均显著下降(P＜0.05).据此推测冷诱导可导致COX Ⅰ基因表达量降低从而产生更多的ATP为机体提供能量抵御寒冷,COX Ⅰ基因可能是一个与猪的抗寒性显著相关的候选基因.     

The novel Sinupret® dry extract exhibits anti-inflammatory effectiveness in vivo

Sinupret® is frequently used as a herbal medicinal product to treat sinusitis, and it was assumed that anti-inflammatory effects might contribute to its overall beneficial properties. Here, we investigated the effects of a Sinupret® drug mixture (SIN) as well as of the novel Sinupret® dry extract (SIN DE) with the latter containing higher concentrations of active ingredients, in an in vivo model of acute inflammation, the carrageenan-induced pleurisy in rats. Both SIN and SIN DE were administered to rats orally at doses of 100 mg/kg (low dose) and 500 mg/kg (high dose) 1 h prior to intrapleural injection of carrageenan. Although both SIN and SIN DE significantly reduced the exudate volume and leukocyte numbers in the pleural exudate at the high and the low dose 4 h after carrageenan injection, the novel SIN DE was more efficient than SIN at the low dose, implying higher efficiency. In parallel, the novel dry extract SIN DE, but not SIN, at 500 mg/kg significantly lowered the levels of prostaglandin (PG)E₂ in the exudates and reduced the amounts of cyclooxygenase (COX)-2 protein in the lungs. Together, SIN and SIN DE exert significant oral anti-inflammatory effects, which rationalize their therapeutic use in the management of sinusitis and other viral/microbial nasal infections that are associated with inflammation. Moreover, our results suggest that based on the higher efficiency and the accompanied reduction of COX-2 expression and PGE₂ formation, the novel dry extract SIN DE might be superior over the former SIN drug mixture.