“棘防E号”的安全性评价Ⅰ——急性毒性试验

90只小鼠随机分为9组，每组10只。除对照组外，其余8组分别以绵羊每日正常用药量的1．5^n等比级数递增剂量，一次给小鼠灌服“刺防E号”，连续观察14天，以测定“棘防E号”对小鼠口服的LD50。结果表明，当小鼠服用绵羊正常用药量的17倍时，不出现半数死亡，说明“棘防E号”对小白鼠的LD50大于绵羊正常用药量的10倍，是完全安全性的药物。     

“棘防A号”的安全性评价

90只小白鼠随机分为9组，每组10只，除对照组外，其余8组分别以绵羊每日正常用药量的1．5n等比级数递增剂量，一次给小白鼠灌服“棘防A号”，连续观察14d，以测定“棘防A号”对小白鼠口服的LD50。结果表明，当小白鼠用绵羊正常用药量的11倍时，不出现半数死亡，说明“棘防A号”对小白鼠的LD50大于绵羊正常用药量的10倍。是安全性的药物。     

“棘防E号”的安全性评价Ⅰ—急性毒性试验

90只小鼠随机分为9组，每组10只。除对照组外，其余8组分别以绵羊每日正常用药量的1．5^n等比级数递增剂量，一次给小鼠灌服“棘防E号”，连续观察14天，以测定“棘防E号”对小鼠口服的LD50。结果表明，当小鼠服用绵羊正常用药量的17倍时，不出现半数死亡，说明“棘防E号”对小白鼠的LD50大于绵羊正常用药量的10倍，是完全安全性的药物。     

“棘防E号”诱发小白鼠骨髓细胞的微核效应

采用微核试验观察“棘防E号”对小鼠骨髓细胞遗传毒性作用和量效关系。结果表明,“棘防E号”剂量为1/2 LD50(1 404 mg/kg)、1/4LD50(702 mg/kg)、1/8 LD50(352 mg/kg)时微核率分别为(140.27±4.71)%、(64.04±3.07)%、(42.01±1.99)%。其中1/2 LD50(1 404mg/kg)剂量组的微核率是阴性对照组的3.2倍,说明“棘防E号”的剂量超过1/2 LD50以上时对小白鼠骨髓细胞有一定的致突变作用。     

“棘防E号”对小鼠的急性毒性试验

对昆明种小鼠经口灌服“棘防E号”进行急性毒性试验，按简化机率单位法测得“棘防E号”对小鼠的LD50为2808mg／kg，LD50的95％的可信限为2015mg／kg-3905mg／kg，表明“棘防E号”为低毒物质。     

“棘防E号”对小白鼠精子畸形率的影响

将"棘防E号"分别按每千克体重176(1/16 LD50),352(1/8 LD50),702(1/4 LD50)和1 404 mg(1/2 LD50)剂量给小鼠灌服,研究其对雄鼠精子的损害作用。结果表明:1/2 LD50组、1/4 LD50组的精子畸形率是阴性对照组(蒸馏水)的5.4倍和2.6倍,且各剂量之间和精子畸形率呈明显线性相关(r=0.9979)。说明当"棘防E号"的剂量达到每千克体重702 mg时,对小白鼠的精子具有明显的损害作用。     

大鼠及小白鼠口服多拉菌素的急性毒性试验

采用递增法预试测得大鼠和小白鼠口服多拉菌素LD0值依次为5．37g／kg．BW、3.54g／kg．BW，LD100值依次为13、91g／kg．BW、6．19g／kg．BW，依之按简化寇氏法分组正式试验，统计死亡率，计算出大鼠和小白鼠口服多拉菌素LD50值依次为7．67g／kg．BW、4．58g／kg．BW，其95％可信限依次为7．22—8．12g／kg．BW、3．80—5．50g／kg．BW。     

“棘防E号”对小鼠的急性毒性试验

对昆明种小鼠经口灌服“棘防E号”进行急性毒性试验。按简化机率单位法测得“棘防E号”对小鼠的LD_(50)为2 808 mg/kg;LD_(50)的95％的可信限为2 015～3 905 mg/kg,表明“棘防E号”为低毒物质。     

国产替米考星对小白鼠的急性毒性试验

采用简化寇氏法对国产替米考星在小白鼠上进行了口服急性毒性试验，结果表明，其：LD50为2071mg／kg，LD50的95％可信限为1932—2219mg／kg。对小白鼠剖检结果表明，该药对内脏器官无病理损害作用，动物口服替米考星毒性很低，临床使用较完全。     

英得尔种羊场放牧绵羊棘豆中毒预防效果初报

对放牧绵羊自然棘豆中毒羊群采用补饲、"轮牧法”和应用棘豆中毒预防药物"棘防A号”、"棘防B号”和"棘防E号”综合措施预防绵羊棘豆中毒,使羊群因棘豆中毒引起的死亡和淘汰羊明显减少,所产羔羊数及繁活数明显增加.     

复方吡喹酮注射液防治羊脑多头蚴病的试验研究

为了获得复方吡喹酮注射液治疗羊脑多头蚴病的最佳治疗剂量,本试验应用复方吡喹酮注射液30、50、80 mg/kg BW三个剂量组对患羊脑多头蚴病的绵羊进行治疗,设80 mg/kg BW剂量的丙硫咪唑作为药物对照组.试验结果表明,30 mg/kg BW剂量组治愈率较低,为68.97%,不能达到治疗目的;50和80 mg/kg BW剂量对羊脑多头蚴均有很强的驱杀作用,对病羊的治愈率分别为91.84%和92.85%,但两组间差异不显著(P＞0.05);高、中剂量组(80、50 mg/kg BW)与低剂量组、药物对照组比较差异极显著(P＜0.01).50 mg/kg BW剂量为防治羊脑多头蚴病的最佳治疗剂量.     

氟苯尼考混悬型微乳剂的急性毒性试验

为评价氟苯尼考混悬型微乳剂的安全性,按改良寇氏法进行了氟苯尼考混悬型微乳剂的急性毒性试验。根据预实验结果,60只小鼠平均分为6组,雌雄各半,分别按6000、4558.5、3464、2632、2000 mg/kg氟苯尼考混悬型微乳剂和0.5 mL/kg生理盐水注射液给小鼠腹腔一次性注射,同时用氟苯尼考普通注射液做对照,重复上述试验,均连续观察7 d。结果显示：氟苯尼考混悬型微乳剂最大耐受量为6000 mg/kg,其LD50为3658.8 mg/kg,LD5095%可信限为2075.8～5241.8 mg/kg。氟苯尼考注射液的LD50为636.68 mg/kg,LD5095%可信限为538.5～735.1 mg/kg。此剂量氟苯尼考混悬型微乳剂中氟苯尼考的含量相当于临床推荐用量（20 mg/kg）的180倍,表明氟苯尼考混悬型微乳剂毒性显著降低,在治疗剂量范围内使用安全。     

Effect of ibuprofen on coccidiosis in broiler chickens

Ibuprofen (IBU)-a nonsteroidal anti-inflammatory drug-inhibits the biosynthesis of prostaglandins with pro-inflammatory and immunosuppressive properties and is therefore proposed as a candidate molecule for the treatment of coccidiosis in broiler chickens. In all experiments, IBU was administered via drinking water. In a first experiment, chickens were infected at 10 or 21 days of age with oocysts of Eimeria acervulina (5 X 10(4)), Eimeria maxima (3 X 10(4)), and Eimeria tenella (7.5 X 10(3)) and medicated with IBU at a dose of 15 mg/kg body weight (BW). In a second experiment, chickens were infected at 6 days of age with 10(4) oocysts of E. acervulina and medicated with IBU at a dose of 100 mg/kg BW. In the third experiment, an inoculum consisting of 5 x 10(4) or 10(5) E. acervulina oocysts was administered at 6 days of age to chickens medicated with IBU at a dose of 100 mg/kg BW. In a fourth experiment, the effect of IBU on sporulation and infectivity of E. acervulina oocysts was studied. Coccidial lesion scores (CLSs), oocyst shedding, and weight gain were used as evaluation parameters in all experiments except the fourth, where weight gain was not taken into account. In addition, the sporulation percentage was determined in the last experiment. No influence of IBU on the indicated parameters was observed after providing the drug at a dose of 15 mg/kg BW, whereas CLSs and oocyst shedding were reduced when IBU was provided at a dose of 100 mg/kg BW. However, IBU did not significantly show any effect on the degree of sporulation and infectivity of E. acervulina oocysts at a dose of 100 mg/kg BW.     

The effect of opioid and acepromazine premedication on the anesthetic induction dose of propofol in cats

The median effective dosage (ED50) for induction of anesthesia with propofol was determined by using the up-and-down method in 31 unpremedicated cats, in 30 cats premedicated with butorphanol, 0.4 mg/kg body weight (BW), and acepromazine, 0.1 mg/kg BW, intramuscularly, and in 30 cats premedicated with morphine, 0.2 mg/kg BW, and acepromazine, 0.1 mg/kg BW, intramuscularly. The dose required for a satisfactory anesthetic induction in 50% of unpremedicated cats (ED50) was 7.22 mg/kg BW and of premedicated cats was 5.00 mg/kg BW. The reduction in dose was statistically significant in both premedicated groups compared with no premedication. There was no significant difference in ED50 between premedication regimes. Cyanosis was the most common adverse effect observed in all groups following anesthetic induction with propofol.     

Dose determination and confirmation of a long-acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease

The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil(R) 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1-8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study 3 this dose was judged to be at the beginning of an efficacious dose range for the treatment of BRD when compared with tilmicosin. In Study 4, day 28 treatment success rates were higher for CCFA-SS at 4.4-8.8 CE/kg BW than for tilmicosin (P=0.002) or the noneffective CCFA-SS dose of 1.1 mg CE/kg BW (P < 0.001). Based on decision criteria for Study 4, the effective dose was determined to be 4.4-5.5 mg CE/kg BW. These clinical studies demonstrated that a single dose of CCFA-SS (100 mg CE/mL) administered subcutaneously (s.c.) in the neck at 4.4-5.5 mg CE/kg BW is an effective treatment for BRD in feedlot cattle. However, this route of administration is no longer being considered for this formulation because of the ceftiofur residues that are present at the injection site for extended periods of time.     

利福昔明乳房注入剂对小鼠的急性毒性试验

为评估利福昔明乳房注入剂的急性毒性,采用标准的急性毒性试验方法进行了利福昔明乳房注入剂对小鼠的急性毒性试验。结果表明,最高组剂量达到5 000 mg/（kg·BW）时,小鼠未见不良反应,饮食活动正常,观察期内均未出现死亡,即利福昔明乳房注入剂对小鼠经口灌胃的LD50大于5 000 mg/（kg·BW）,属于实际无毒级物质。     

Determination of the acute 50% lethal dose T-2 toxin in adult bobwhite quail: additional studies on the effect of T-2 mycotoxin on blood chemistry and the morphology of internal organs

Three experiments were conducted to assess mortality rate, blood chemistry, and histologic changes associated with acute exposure to T-2 mycotoxin in adult bobwhite quail. In Experiment 1, adult quail were orally dosed with T-2 toxin to determine the lethal dose that resulted in 50% mortality of the affected population (LD50), and that dose was determined to be 14.7 mg of T-2 toxin per kilogram of body weight (BW). A second experiment was performed to study the effects of 12-18 mg/kg BW T-2 toxin on blood chemistry and liver enzyme profiles. Posttreatment uric acid, aspartate aminotransferase, lactic dehydrogenase, and gamma glutamyltransferase increased as compared with pretreatment values. In contrast, posttreatment plasma total protein, cholesterol, and triglyceride levels numerically decreased as compared with pretreatment values. Changes in blood chemistry values were consistent with liver and kidney damage after T-2 toxin exposure. In Experiment 3, histologic analyses of bone marrow, spleen, liver, small intestine, kidney, and heart were conducted on birds dosed in Experiment 2. Marked lymphocyte necrosis and depletion throughout the spleen, thymus, bursa, and gut-associated lymphoid tissue in the small intestine were observed in birds dosed with 15 and 18 mg/kg BW T-2 toxin. Necrosis of liver and lipid accumulation as a result of malfunctioning hepatocytes were also observed. Little or no morphologic change was observed in bone marrow and heart tissue. The LD50 for adult bobwhite quail as found in this study is two to three times higher than that reported for other species of commercial poultry. Results from these data confirm previous reports of immunosuppressive and/or cytotoxic effects of T-2 toxin in other mammalian and avian species. T-2 toxin may have a negative impact on the viability of wild quail populations.     

Anticoccidial effects of <Emphasis Type="Italic">Aloe secundiflora</Emphasis> leaf extract against <Emphasis Type="Italic">Eimeria tenella</Emphasis> in broiler chicken

Anticoccidial effects of Aloe secundiflora crude leaf extract was tested in broiler chickens following oral infection with Eimeria tenella. Sixty 22-day-old birds were divided into six groups of ten birds each. Three treatment groups A, B, and C were fed with the extract (100, 250, and 500 mg/day, respectively) mixed in feed for 10 days, and three control groups: group D (drug control) administered 300 mg/l of sulfachloropyrazine sodium soluble powder in drinking water for 5 days, group E (infected/non-medicated positive control), and group F (uninfected/non-medicated negative control). Except for group F, all groups were orally inoculated with 75,000 sporulated oocysts of E. tenella. The effects of the extract on E. tenella infection were evaluated by severity of bloody diarrhea, body weight (BW) gain, oocyst output, and lesion score. No bird in the treated groups died of coccidiosis, and severity of bloody diarrhea was milder than in the positive control group. BW gains in the treated groups were significantly higher than in group E (p < 0.05). The lesion scores of the treated groups were significantly lower than that of group E. Oocyst output in groups A, B, and C were 11.23, 8.24, and 6.82 × 10⁶, respectively. As compared with the negative control group (12.84 × 10⁶), the reductions in oocyst production were 12.54, 35.83, and 46.88%, respectively. Oocyst output significantly reduced with an increase in Aloe dosage. The findings of this study suggest that Aloe secundiflora extract presents an alternative anticoccidial agent for the control of avian coccidiosis.     

Seasonal changes in the interactions among leptin, ghrelin, and orexin in sheep

The adaptation of the physiology of an animal to changing conditions of light and food availability is evident at the behavioral and hormonal levels. Melatonin, leptin, ghrelin, and orexin, which exhibit rhythmic secretion profiles under ad libitum feeding conditions, are sensitive to changes in daylength, forming a tight web of interrelationships in the regulation of energy balance. The aim of this study was to determine the effects of central injections of leptin, ghrelin, and orexin on the reciprocal interactions among these hormones and the influence of photoperiod on these responses. Twenty-four ovariectomized and estradiol-implanted ewes were used in a replicated switchback design. The ewes were assigned randomly to 1 of 6 treatment groups, and the treatments were infused into their third ventricles 3 times at 0, 1, and 2 h, with 0 h being at dusk. The treatments were as follows: 1) control, Ringer-Locke buffer; 2) leptin, 0.5 μg/kg BW; 3) ghrelin, 2.5 μg/kg BW; 4) orexin B, 0.3 μg/kg BW; 5) leptin antagonist, 50 μg/kg BW, then ghrelin, 2.5 μg/kg BW; and 6) leptin antagonist, 50 μg/kg BW, then orexin B, 0.3 μg/kg BW. Blood samples (5 mL) were collected at 15-min intervals for 6 h. The administration of leptin increased (P < 0.05) plasma concentrations of melatonin during short-day (ShD) photoperiods and decreased (P < 0.05) them during long-day (LD) photoperiods, whereas ghrelin decreased (P < 0.05) melatonin concentrations during ShD photoperiod, and orexin had no effect (P > 0.1). Leptin attenuated (P < 0.05) ghrelin concentrations relative to the concentration in controls during ShD. The plasma concentrations of orexin were reduced (P < 0.05) after leptin infusions during LD and ShD photoperiods; however, ghrelin had the opposite effect (P < 0.05) on orexin concentration. Orexin increased (P < 0.05) ghrelin concentrations during LD. Ghrelin and orexin concentrations were increased (P < 0.05) after leptin antagonist infusions. Our data provide evidence that the secretion of leptin, ghrelin, and orexin are seasonally dependent, with relationships that are subject to photoperiodic regulation, and that leptin is an important factor that regulates ghrelin and orexin releases in sheep.     

Disposition of gentamicin in the genital tract of cows

The distribution of gentamicin (G) in plasma and uterine lumen was studied following intramuscular (i.m.) and intrauterine (i.u.) treatment. A Foley catheter was inserted into one uterine horn and retained in place by inflation of the cuff. This provided a closed system for collection of uterine lumen samples and analysis of the concentration of gentamicin for 6 h following treatment. Four normal cycling and healthy cows in dioestrus were given i.m. injections of 4 mg gentamicin/kg BW and another two were given i.m. injections of 2 mg gentamicin/kg BW gentamicin. The uteri were infused with 50 ml saline containing phenolsulphonphthalein (PSP) indicator. Blood and infused solution (IS) samples were periodically collected during the 6-h period following i.m. administration. Six hours after injection, approximately 183.7 micrograms gentamicin and 39.4 micrograms gentamicin were accumulated in the uterine lumen of cows receiving 4 mg gentamicin/kg BW and 2 mg gentamicin/kg BW, respectively. The amount of gentamicin reaching the blood stream after i.m. administration of 4 mg gentamicin/kg BW was 2.89 times that reached after administration of 2 mg gentamicin/kg BW based on the area under the curve of plots of plasma concentration of gentamicin versus time. Four normal-cycling and healthy cows in dioestrus were given i.u. infusions of gentamicin (225-275 mg) diluted in 50 ml saline containing PSP indicator using a Foley catheter in a closed system. Samples from the IS and blood were collected at various intervals for 6 h after infusion. Following i.u. infusion of gentamicin, an average of 29.4% of the dose was absorbed into the bloodstream. The majority of the dose of gentamicin (70.6%) remained in the uterine lumen throughout the 6-h period.