Tumor necrosis factor‐α‐induced inflammatory responses in cattle

Tumor necrosis factor‐alpha (TNF‐α) is recognized as a cytokine because of its involvement in inflammation‐mediated biological defense functions. Although TNF‐α is primarily produced by macrophages, it is also produced by other cells, including lymphocytes, Kupffer cells, natural killer cells and adipocytes. While TNF‐α has diverse immune system functions, including antitumor activity, antimicrobial activity and mediation of inflammation, it also regulates a number of physiological functions, including appetite, fever, energy metabolism and endocrine activity. Factors such as viruses, parasites, other cytokines, and endotoxins induce TNF‐α production. In combination with other cytokines, TNF‐α plays a clinically important role in cattle by mediating immune inflammatory responses such as mastitis and endotoxic shock. It has been reported that cytokines such as TNF‐α are involved in metabolic disease such as acidosis. On the other hand, several data suggest that lactoferrin (LF) acts to prevent the release of a number of inflammatory mediators from various activated cells, and further suggest that the prophylactic effect of LF involves inhibition of cytokine production, including TNF‐α, that are principal mediators of the inflammatory response leading to death from toxic shock. This review discusses the role of TNF‐α in pathological conditions in cattle, including infections and metabolic diseases caused by perturbation of metabolism and endocrine functions.     

药典方剂止痢散的毒理学研究

为了从现代药理学角度评价止痢散临床用药的安全性,对其进行了毒理学研究。通过小鼠灌胃给药对止痢散的急性毒性进行了测定;以生理盐水对照组、止咳散低剂量组（4 g/kg）、中剂量组（8 g/kg）、高剂量组（16 g/kg）对大鼠连续灌胃给药4周,记录每日饮水量、饲料采食量及每周体重,测定末次给药后24 h及停药2周后血液生化指标及血常规,做病理切片,评定其长期毒性。结果显示：小鼠口服止痢散的LD50为124.8g/kg,95%可信限111.2～142.5 g/kg,单味雄黄的LD50为10.5 g/kg,95%可信限9.7～11.1 g/kg;且对大鼠连续灌胃给药4周期间,止痢散低剂量组大鼠没有出现可见的毒性反应;中、高剂量组大鼠呈现出明显毒性反应,具体表现为采食及饮水量减少,体重减轻,消化道充血、出血,肝脏存在炎性细胞浸润、肝细胞水泡变性,肾脏、心脏轻度出血,血清尿素氮、谷丙转氨酶、谷草转氨酶、与碱性磷酸酶升高等;不过高剂量组大鼠用药期间也没有出现死亡;上述毒性反应在停药2周后基本消失。以上结果表明,止痢散的毒性较低,按兽药典规定剂量用药是安全的,但长期使用能引起蓄积作用,造成肝肾损伤,其毒性具有可逆性。     

Acute myeloid leukaemia (M6B: pure acute erythroid leukaemia) in a Thoroughbred foal

A 10-week-old Thoroughbred filly was referred for anaemia of 4 weeks' duration. Haematology revealed severe anaemia and panleucopenia. Cytological examination of bone marrow smears revealed a myeloid to erythroid ratio <0.02:1 (reference range 0.5-2.4:1.0) and an abundance of erythroid precursor cells. The erythroid cell population included rubriblasts, prorubricytes and rubricytes, with only scant numbers of metarubricytes present. There were numerous mitotic erythroid cells, some of which were atypical and megaloblastic. These cytomorphological changes are consistent with pure acute erythroid leukaemia. No treatment was instituted and the filly died three days after presentation. This case illustrates the need to consider both haematology and bone marrow findings to establish a diagnosis of pure erythroid leukaemia. To our knowledge, there is no documented case of acute myeloproliferative disease in horses involving cells of erythroid lineage, but this condition should be considered a differential diagnosis for horses presenting with anaemia.     

Antagonistic effect of angiotensin II type 1 receptor blocker candesartan on angiotensin II-induced proliferation of primary acute myeloid leukemia cells

AIM: To explore the antagonistic effect and mechanism of candesartan on angiotensin II (Ang II)-induced proliferation of primary acute myeloid leukemia (AML)cells. METHODS: MTT assay was used to observe the proliferation effect of Ang II on primary AML cells and normal bone marrow mononuclear cells, and the antagonistic effects of candesartan and PD123319 (an antagonist of AT2R) were also observed. Akt phosphorylation was detected by Western blotting when the cells were treated with candesartan and a PI3K inhibitor LY294002.RESULTS: Compared with the control cells, Ang II significantly increased the proliferation of AML cells in a dose-and time-dependent manner (P<0.05). Ang II did not stimulate the proliferation of normal bone marrow mononuclear cells. The proliferative effect of Ang II was effectively blocked by the AT1R blocker candesartan (P<0.05). PI3K inhibitor strongly repressed the Ang II-induced cell proliferation (P<0.05). Candesartan significantly reduced Akt phosphorylation promoted by Ang II on primary AML cells (P<0.05).CONCLUSION: Candesartan effectively inhibits Ang II-induced proliferation of primary AML cells by down-regulating PI3K/Akt signaling pathway, indicating a new possible treatment mechanism in some AML cells.     

Acute toxicity and bioconcentration of pyrimorph in zebrafish,Brachydanio rerio

BACKGROUND: Pyrimorph is a novel fungicide being developed in China that shows high antifungal activity against diseases caused by Phytophthora infestans, Phytophthora capsici, Rhizoctonia solani, Peronophythora litchi and Pseudoperonospora cubensis. Until now, no information on the toxicity of pyrimorph to untargeted organisms has been reported. To assess the potential environmental impacts of pyrimorph in fish, the acute toxicity and bioconcentration of pyrimorph in zebrafish were studied in this paper. RESULTS: When tested by the semi‐static method, the 48, 72 and 96 h median lethal concentration (LC₅₀) values of pyrimorph to zebrafish were 24.33, 22.61 and 19.79 mg L^?1 respectively. To study the bioconcentration of pyrimorph in zebrafish, the fish were exposed to sublethal concentrations of pyrimorph (2.00 and 0.25 mg L^?1) for 192 h, a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method was applied to extract pyrimorph from samples and the residues of pyrimorph in the water and fish were determined by high‐performance liquid chromatography (HPLC). The highest bioconcentration factor (BCF) of pyrimorph in the fish was 1.07 × 10² (144 h) and 23.1 (96 h) after exposure to 2.00 and 0.25 mg L^?1 of pyrimorph respectively. CONCLUSIONS: The novel fungicide pyrimorph has low toxicity to zebrafish; however, it showed medium BCF to zebrafish. Therefore, more attention should be paid to the residue of pyrimorph in fish, as well as to its long‐term ecological effects. Copyright © 2011 Society of Chemical Industry     

兽药添加剂阿散酸和土霉素的毒理学研究

采用斑马鱼和鲫鱼作为生物材料,分别研究了兽药添加剂阿散酸和土霉素对斑马鱼的急性毒性及对鲫鱼肾细胞DNA损伤。急性毒性试验表明,阿散酸和土霉素的斑马鱼96hLC50分别为520.747和1341.764mg·L-1。彗星试验结果表明,阿散酸引起的DNA损伤较小,与阴性对照相比无显著性差异(P>0.05);而土霉素能引起较大的DNA损伤,与阴性对照相比均有极显著性差异(P<0.01)     

喹乙醇对蚯蚓的毒理学研究

以滤纸染毒和溶液染毒法研究了喹乙醇对蚯蚓的急性毒性效应以及对其生长的影响。结果表明,滤纸染毒和溶液染毒48h的致死中浓度(LC50)分别为1.02mg.cm-2和>4000mg.L-1,喹乙醇能引起蚯蚓的形态病理变化。低浓度喹乙醇(500、1000mg.kg-1)对蚯蚓的体重增长率没有显著影响(P>0.05),高浓度喹乙醇(3000、5000mg.kg-1)能极显著降低蚯蚓体重增长率(P<0.01)。检测暴露喹乙醇14d的蚯蚓体和不同部位的过氧化氢酶(CAT)活性,结果发现,高浓度喹乙醇能显著抑制蚯蚓体及其前部和中部CAT的活性,低浓度喹乙醇只对蚯蚓前部的CAT活性表现出显著抑制(P<0.05)。     

Biomarkers of Inflammation in Exotic Pets

The acute phase response (APR) is a key part of the innate immune system and acute phase proteins (APPs) represent the core of the early response to stimuli such as trauma, infection, stress, neoplasia, and autoimmune disease. These biomarkers have a different timeline and magnitude of expression vs traditional means of examining inflammation (e.g., total white blood count and albumin/globulin (A/G) ratio). Extensive studies conducted in companion and large animals have demonstrated many clinical applications for inflammatory biomarkers including diagnosis, prognosis, detection of subclinical disease and chronic inflammation, and monitoring stress. This article provides information regarding the APR and the uses of APP quantitation, as well as the growing body of information on APPSs in exotic animals.