Evaluation of biomarkers of kidney injury following 4% succinylated gelatin and 6% hydroxyethyl starch 130/0.4 administration in a canine hemorrhagic shock model

Objective : To investigate the association between synthetic colloids and biomarkers of acute kidney injury (AKI) in dogs with hemorrhagic shock. Design : Experimental interventional study. Setting : University. Animals : Twenty‐four healthy ex‐racing Greyhounds. Interventions : Anesthetized Greyhounds subjected to hemorrhage for 60 min were resuscitated with 20 mL/kg of fresh whole blood (FWB), 6% hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL/kg of isotonic crystalloid (CRYST) over 20 min (n = 6 per treatment). Concentrations of biomarkers of AKI were measured at baseline, end of hemorrhage, and at 40 (T60), 100 (T120), and 160 (T180) min after fluid bolus. Biomarkers included neutrophil gelatinase‐associated lipocalin in urine and serum (uNGAL; sNGAL), and urine cystatin C (uCYSC), kidney injury molecule‐1 (uKIM), clusterin (uCLUST), osteopontin, gamma‐glutamyl transferase, monocyte chemoattractant protein‐1 (uMCP), interleukin‐6, interleukin‐8, protein (uPROT), hyaluronan, and F₂‐isoprostanes. Renal histology was scored for tubular injury and microvesiculation. Biomarker fold‐change from baseline was compared between groups using mixed effects models (Bonferroni–Holm corrected P<0.05). Frequencies of histology scores were compared by Fisher's exact test. Measurements and main results : In dogs treated with GELO, uNGAL fold‐change was markedly greater compared with all other groups at T60, T120, and T180 (all P<0.001), and uCYSC was greater at T60 compared with CRYST (P<0.001), and at T120 and T180 compared with all other groups (all P<0.001). Smaller, albeit significant, between‐group differences in uKIM, uCLUST, uMCP, and urine protein concentration were observed across the FWB, GELO, and HES groups, compared with CRYST. The GELO group more frequently had marked tubular microvesiculation than the other groups (P = 0.015) although tubular injury scores were comparable. Conclusion : In dogs with hemorrhagic shock, GELO was associated with greater magnitude increases in urine biomarkers of AKI and more frequent marked tubular microvesiculation, compared with FWB, CRYST, and HES.     

骨质疏松症治疗药物的研究进展

骨质疏松症是以骨量减少、骨的微观结构退化为特征,致使骨的脆性增加并易于发生骨折的一种全身性骨骼疾病,是当前严重危害人类特别是绝经妇女和老人的疾病之一.近年来出现了许多预防和治疗骨质疏松症的药物,极大地推动了骨质疏松症理论基础的完善和临床治疗研究.就该领域的研究进展进行了简要综述.     

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.     

Canine corneal fibroblast and myofibroblast transduction with AAV5

Objective The aims of this study were (1) to determine the efficacy of adeno‐associated vector serotype 5 (AAV5) for delivering gene therapy to canine corneal fibroblasts (CCFs) and myofibroblasts (CCMs) using enhanced green fluorescent protein (GFP) marker gene and (2) to evaluate the cytotoxicity of AAV5 to CCFs and CCMs using an in vitro model. Methods Healthy donor canine corneas were used to generate primary CCFs by growing cultures in minimal essential medium supplemented with 10% fetal bovine serum. Canine corneal myofibroblasts were produced by growing cultures in serum‐free medium containing transforming growth factor β1 (1 ng/mL). An AAV5 titer (6.5 × 10¹² μg/mL) expressing GFP under control of hybrid cytomegalovirus + chicken β‐actin promoters (AAV5‐gfp) was used to transduce CCF and CCM cultures. Delivered gene expression in CCFs and CCMs was quantified using immunocytochemistry, fluorescent microscopy, and real‐time PCR. Transduction efficacy of the AAV5 vector was determined by counting DAPI‐stained nuclei and EGFP‐positive cells in culture. Phase‐contrast microscopy, trypan blue, and dUTP nick end labeling (TUNEL) assays were used to determine the toxicity and safety of AAV5 in this canine corneal model. Results Topical AAV5 application successfully transduced a significant population of CCFs (42.8%; P < 0.01) and CCMs (28%; P < 0.01). Tested AAV5 did not affect CCF or CCM phenotype or cellular viability and did not cause significant cell death. Conclusions The tested AAV5 is an effective and safe vector for canine corneal gene therapy in this in vitro model. In vivo studies are warranted.     

不同中西药方剂治疗猪附红细胞体病的效果试验

配制三种浓度的血虫净、盐酸土霉素、中药制剂及其两两相互组合三个复方共 1 2种药物方剂组 ,对猪附红细胞体病的病例进行治疗试验。结果表明 ,血虫净 中药制剂组疗效最佳 ,经治疗 6d后红细胞感染率显著低于其他组( P <0 .0 5或 P <0 .0 1 ) ,且死亡率为零 ,治疗愈率达到 1 0 0 % ;中药制剂组红细胞感染率、死亡率显著高于其余组 ( P <0 .0 5或 P <0 .0 1 ) ,而治愈率、有效率低于其余组。证明中草药与西药合用有协同增效作用。     

益生菌对类风湿关节炎的改善作用研究进展

类风湿关节炎是一种威胁全球人类健康的自身免疫性疾病,肠道菌群的平衡与类风湿关节炎密切相关。由于益生菌在改善肠道菌群紊乱、恢复正常肠道菌群中发挥重要作用,因此给益生菌治疗类风湿关节炎提供了可能。本文综述类风湿关节炎病因、机制及患者肠道菌群的变化,总结近年来益生菌在治疗类风湿关节炎中的研究现状,为进一步临床试验和今后的应用提供依据。     

Pulse pressure variation as a guide for volume expansion in dogs undergoing orthopedic surgery

Objective

To investigate whether pulse pressure variation (PPV) can predict fluid responsiveness in healthy dogs during clinical surgery.