Promotion of liver and kidney carcinogenesis by ethyl tertiary-butyl ether (ETBE) in male Wistar rats

Tumor-promoting effects of ethyl tertiary-butyl ether (ETBE) were investigated in a 2-stage carcinogenesis bioassay with regard to hepatic and renal carcinogenesis in rats. Male 6-week-old Wistar rats were given drinking water containing N-ethyl-N-(2-hydroxyethyl)nitrosamine (EHEN), as an initiator, at a dose of 500 ppm for 2 weeks. Starting one week thereafter, the animals were administered ETBE at dose levels of 0 (control), 100, 300, 500 or 1,000 mg/kg/day by gavage for 19 weeks from week 4 to 22. Necropsy of all rats was performed at week 23, and livers and kidneys were examined histopathologically. Incidences of hepatocellular adenomas, and those of combined hepatocellular adenomas and carcinomas were significantly elevated in rats given 1,000 mg/kg/day ETBE, but not 100‒500 mg/kg/day ETBE, and there was a significant increase in the average numbers of lesions. No significant differences in incidences and average numbers of renal tubule neoplasms were found in rats administered 100‒1,000 mg/kg/day ETBE. However, the average numbers of atypical tubule hyperplasias, considered to be preneoplastic lesions, were significantly increased in rats given ETBE at 1,000 mg/kg/day, but not in rats given 500 mg/kg/day or lower doses. Thus, these results imply that ETBE has hepatic and renal tumor-promoting activities that affect EHEN-induced carcinogenesis in male rats, and the no-observed-effect level is 500 mg/kg/day under the present experimental conditions.     

Maternal and foetal immune responses of cattle following an experimental challenge with Neospora caninum at day 70 of gestation

The immune responses of pregnant cattle and their foetuses were examined following inoculation on day 70 of gestation either intravenously (iv) (group 1) or subcutaneously (sc) (group 2) with live NC1 strain tachyzoites or with Vero cells (control) (group 3). Peripheral blood mononuclear cell (PBMC) responses to Neospora antigen and foetal viability were assessed throughout the experiment. Two animals from each group were sacrificed at 14, 28, 42 and 56 days post inoculation (pi). At post mortem, maternal lymph nodes, spleen and PBMC and when possible foetal spleen, thymus and PBMC samples were collected for analysis. Inoculation with NC1 (iv and sc) lead to foetal deaths in all group 1 dams (6/6) and in 3/6 group 2 dams from day 28pi; statistically significant (p ≤ 0.05) increases in cell-mediated immune (CMI) responses including antigen-specific cell proliferation and IFN-γ production as well as increased levels of IL-4, IL-10 and IL-12 were observed in challenged dams compared to the group 3 animals. Lymph node samples from the group 2 animals carrying live foetuses showed greater levels of cellular proliferation as well as significantly (p ≤ 0.05) higher levels of IFN-γ compared to the dams in group 2 carrying dead foetuses. Foetal spleen, thymus and PBMC samples demonstrated cellular proliferation as well as IFN-γ, IL-4, IL-10 and IL-12 production following mitogenic stimulation with Con A from day 14pi (day 84 gestation) onwards. This study shows that the generation of robust peripheral and local maternal CMI responses (lymphoproliferation, IFN-γ) may inhibit the vertical transmission of the parasite.     

The effects of flubendazole and mebendazole on cytochromes P4501A in pheasant hepatocytes

Many benzimidazoles are known inducers of cytochromes P4501A (CYP1A) in laboratory animals and cell lines. As flubendazole and mebendazole are benzimidazole anthelmintics often used in a pheasant, in the present study an effect of these drugs in primary cultures of pheasant (Phasianus colchicus) hepatocytes was investigated. After 48 h incubation of the hepatocytes with the benzimidazoles (0.2-5 microM), CYP1A activities -- ethoxyresorufin O-deethylation (EROD) and methoxyresorufin O-demethylation (MROD) activities were measured and the CYP1A protein levels were determined by Western blotting. None of the tested benzimidazoles influenced the CYP1A protein content. No pharmacologically significant enhancement of CYP1A after exposure of the hepatocytes to flubendazole and mebendazole was found. Inhibition of the EROD/MROD activities caused by both tested substances was observed only at the highest concentration (5 microM). From a point of view of CYP1A induction or inhibition, the treatment of pheasants by both anthelmintics tested seems to be safe. Our study demonstrates the inter-species differences in CYP1A inducibility and the importance of induction/inhibition studies on target animals.     

The effect of dimethoate and pyrantel on vitamin C concentration in the rat liver

The aim of this study was to determine the content of vitamin C in the liver of rats exposed to dimethoate or pyrantel embonate as well as co-intoxication with both agents. Investigations were carried out in two stages. At each stage, the rats were divided into three experimental groups (I-III) and a control (C) group. In the first stage, rats from group I were administered pyrantel embonate at a two-week interval at a dose of 1/2 LD50, while the animals from group II received dimethoate for 28 days at a dose of 1/25 LD50, and those from group III - both mentioned compounds in an identical manner as in groups I and II. In the second stage, the rats from group I received pyrantel embonate at a dose of 1/5 LD50 for 3 consecutive days, while the animals from group II received dimethoate at a dose of 1/10 LD50 for 5 consecutive days, and those from III received both compounds, but pyrantel was administered on day 3, 4 and 5 of dimethoate administration. The concentration of vitamin C after pyrantel embonate and dimethoate administration was influenced not only by doses of the compounds used but also by the manner of their application (single or co-administration). Dimethoate delivered at a dose of 1/25 LD50 evoked an increase in vitamin C concentration that was observed to continue up to the 14th day after the exposure, whereas when applied at a dose of 1/10 LD50 it increased the vitamin C level only at the 3rd hour. A considerable decrease in the vitamin C level was reported after pyrantel treatment at a dose of 1/5 LD50. In rats from groups where the compounds were co-administered, increased level of vitamin C was observed at both stages of the experiment only in the first period after intoxication, i.e. up to the 6th hour.     

No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE) on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine

The effects of ethyl tertiary-butyl ether (ETBE) on two-stage urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated at various dose levels with regard to possible promoting activity. Groups of 30 rats were given drinking water containing 500 ppm BBN, as an initiator, for 4 weeks and starting one week thereafter received ETBE by gavage (daily, 7 days/week) at dose levels of 0 (control), 100, 300, 500 or 1000 mg/kg/day until experimental week 36. No statistically significant differences in incidences of preneoplastic lesions, papillomas, and carcinomas of the urinary bladder were evident in rats treated with 100–1000 mg/kg/day ETBE as compared with control values. Furthermore, the average numbers of preneoplastic or neoplastic lesions per unit length of basement membrane in rats given 100–1000 mg/kg/day ETBE were also comparable to control values. However, papillomatosis of the urinary bladder was found in 4 out of 30 rats (13%) in the group given 1000 mg/kg/day ETBE, and soft stones in the urinary bladder were found in 3 out of these 4 rats. The results thus demonstrated that ETBE did not exert promotional activity on urinary bladder carcinogenesis. However, papillomatosis of the urinary bladder developed in small numbers of the rats given ETBE at 1000 mg/kg/day but not in rats given 500 mg/kg/day or lower doses.     

硒化大蒜多糖对环磷酰胺所致免疫抑制鸡的颉颃作用

为探究硒化大蒜多糖对环磷酰胺所致免疫抑制的颉颃作用,将336只11日龄非免疫健康罗曼雏鸡随机均分为7组：空白对照组（BC）、免疫对照组（VC）、环磷酰胺对照组（Cy）、sGPS3、sGPS5、sGPS6和药物对照组（APS）,每组6个重复,每个重复8只鸡。BC组和VC组注射0.5 mL生理盐水,其余组均肌肉注射8 mg/mL环磷酰胺0.5 mL,每天1次,连续3 d;14日龄时,除BC组外,其余组均用新城疫疫苗免疫,同时3个硒大蒜化多糖组分别注射0.5 mL浓度为1 mg/mL的sGPS₃、sGPS₅、sGPS₆,APS组肌肉注射黄芪多糖注射液0.5 mL,Cy组、VC组和BC组注射生理盐水0.5 mL,每天1次,连续3 d,28日龄二免。分别于首免后的第7、14、21、28天,每组随机抽取6只罗曼鸡翼静脉采血,分离血清,β-微量法检测血清ND-HI抗体效价、ELISA法检测血清γ干扰素（IFN-γ）和白细胞介素2（IL-2）含量。称量体重后采集胸腺、脾脏和法氏囊组织并称重,计算免疫器官指数。结果显示,各给药组的血清ND-HI抗体效价、血清IFN-γ和IL-2含量、法氏囊指数均显著高于Cy组（P<0.05）;sGPS₆组血清抗体效价、IFN-γ含量在28 d,血清IL-2含量在21、28 d均显著高于其余各组（P<0.05）;在免疫后21、28 d,4个给药组中sGPS₆组体重、法氏囊指数最高,显著高于其余3个给药组（P<0.05）;在免疫后28 d,4个给药组中sGPS₆组胸腺指数、脾脏指数最高,显著高于其余3个给药组（P<0.05）。结果表明,硒化大蒜多糖对环磷酰胺所致的免疫抑制具有颉颃作用,其中sGPS₆组的活性最高,可作为新型免疫抑制颉颃剂的候选药。     

N -ethyl- N -nitrosourea induces retinal photoreceptor damage in adult rats

Seven-week-old male Lewis rats received a single intraperitoneal injection of N-ethyl-N-nitrosourea (ENU) (100, 200, 400 or 600 mg/kg), and retinal damage was evaluated 7 days after the treatment. Sequential morphological features of the retina and retinal DNA damage, as determined by a TUNEL assay and phospho-histone H2A.X (γ-H2AX), were analyzed 3, 6, 12, 24 and 72 hr, 7 days, and/or 30 days after 400 mg/kg ENU treatment. Activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) was analyzed immunohistochemically by poly (ADP-ribose) (PAR) expression in response to DNA damage of the retina. All rats that received ≥ 400 mg/kg of ENU developed retinal degeneration characterized by the loss of photoreceptor cells in both the central and peripheral retina within 7 days. In the 400 mg/kg ENU-treated rats, TUNEL-positive signals were only located in the photoreceptor cells and peaked 24 hr after ENU treatment. The γ-H2AX signals in inner retinal cells appeared at 24 hr and peaked at 72 hr after ENU treatment, and the PAR signals selectively located in the photoreceptor cell nuclei appeared at 12 hr and peaked at 24 hr after ENU treatment. However, degeneration was restricted to photoreceptor cells, and no degenerative changes in inner retinal cells were seen at any time points. Retinal thickness and the photoreceptor cell ratio in the central and peripheral retina were significantly decreased, and the retinal damage ratio was significantly increased 7 days after ENU treatment. In conclusion, ENU induced retinal degeneration in adult rats that was characterized by photoreceptor cell apoptosis through PARP activity.     

Unique features of bovine lymphocytes exposed to a staphylococcal enterotoxin

We previously demonstrated that stimulation of bovine peripheral blood mononuclear cells (PBMCs) with staphylococcal enterotoxin C (SEC), led to an inversion of the CD4⁺:CD8⁺ T cell ratio and generation of an atypical CD8⁺ T cell subpopulation expressing CD26. In the present study, we examined T cell apoptosis and proliferation profiles of PBMC subpopulations in cultures stimulated with SEC. Unlike when stimulated with concanavalin A, nucleic acid synthesis in bovine PBMC cultures stimulated with SEC was low during the first four days but increased greatly on day 5. In contrast, nucleic acid synthesis in human PBMC cultures stimulated with SEC increased continuously. To investigate the mechanism of delayed bovine T cell proliferation, various cell phenotypes were monitored. The inversion of the bovine CD4⁺:CD8⁺ T cell ratio in PBMC cultures stimulated by SEC was associated with higher proliferation and lower apoptosis of CD8⁺ T cells compared to CD4⁺ T cells. The mRNA levels for interleukin (IL)-4 and IL-13 were sustained over 4 days but IL-12 mRNA levels dropped to background on day 2. These data suggest that SEC induces a prolonged Th-2-biased microenvironment, and together with the inversion of the bovine CD4⁺:CD8⁺ T cell ratios in bovine PBMC cultures with SEC, may in part explain the inability of the mammary immune system to establish an effective response to Staphylococcus aureus infections.     

Residues of dimethoate in the liver and AchE activity in blood of rats after exposure to dimethoate, and dimethoate and pyrantel embonate

The study was aimed at determining the dimethoate residues in the liver and acetylcholinesterase (AChE) activity in blood of rats exposed to dimethoate (individual intoxication), and dimethoate and pyrantel embonate (simultaneous intoxication). The experiment was carried out in two stages where various doses of preparations and exposure manners were used. In the first stage of the experiment, dimethoate (1/25 LD50) was administered to animals per os for 28 days, and pyrantel embonate (1/2 LD550) twice, i.e. on the day 14th and 28th. In the second stage, dimethoate was administered for 5 days (1/10 LD50), and pyrantel embonate (1/5 LD50) on day 3, 4 and 5 from the beginning of dimethoate intoxication. The short presence of the dimethoate residues in the liver of the animals examined was found until the 2nd day after 28-day intoxication (1/25 LD50) and until 14th day after 5-day intoxication (1/10 LD50), however, a distinct decrease in this insecticide residues in the liver of (analysed groups of) rats occurred between the 3rd hour and the 2nd day after exposure. Dimethoate in both applied doses significantly reduced AChE activity in blood. After application of the higher dose, the inhibition of AChE was more pronounced, and the return of its activity to physiological values lasted considerably longer. Co-administration of pyrantel embonate and dimethoate, slightly influenced changes of the parameters analysed, which have been dependent not only on a dose and manner of pyrantel application but also on time which lapsed from exposure.     

Lack of inhibitory effects of several fluoroquinolones on cytochrome P-450 3A activities at clinical dosage in dogs

Inhibitory effects of several fluoroquinolones (FQs) on liver CYP3A activities were examined by in vitro and in vivo tests in dogs. Midazolam (MDZ) hydroxylation rate was used to determine the CYP3A activities in liver microsomes. Enrofloxacin (EFX), ofloxacin (OFX) orbifloxacin (OBFX) and ciprofloxacin (CFX) were tested. None of the FQs changed Vmax, Km or intrinsic clearance (Vmax/Km) of MDZ. For in vivo test, we examined the effects of oral administration of EFX and OFX on the pharmacokinetics of quinidine (QN), a CYP3A substrate. EFX or OFX (10 mg/kg) was administered once a day for 3 days. QN (2 mg/kg) was intravenously injected at 2 h after the final dose of FQs administration. The same dose of QN was intravenously injected 3 weeks before the start of FQs administration for control. Neither EFX nor OFX changed the pharmacokinetic parameters of QN. These in vitro and in vivo consisted results suggest that these FQs lack the inhibitory effects on CYP3A activities in dogs. Hence, given these results, the risk of drug-drug interaction is unlikely to occur between FQs and CYP3A substrates in clinical situation in dogs.     

Changes in haptoglobin, C-reactive protein and pig-MAP during a housing period following long distance transport in swine

The aim of this study was to investigate the effects of a housing period following long distance transport on haptoglobin (Hp), C-reactive protein (CRP) and pig major acute phase protein (pig-MAP) in swine. After transportation, 80 gilts were allotted to group A, B, C, or D. Blood samples were collected on arrival and 28 days later; additional samples were collected from Group C on day 14, and from Group D on days 3, 5 and 14. Acute phase proteins (APPs) in Group A were significantly lower on day 28 than on day 1; the opposite occurred in Group B because of a tail biting episode. In Group C, values remained elevated on day 14 and showed a reduction on day 28; in Group D elevated levels detected on day 14 were preceded by a decrease from days 1 to 5. The results indicate that stressors associated with transportation and new accommodation can cause an increase in APPs that could be useful indicators of welfare during transport and routine management.     

Prophylactic treatment with flumethrin,a pyrethroid (Bayticol?, Bayer), against Anaplasma phagocytophilum infection in lambs

Backgroud

Anaplasma phagocytophilum (formerly Ehrlichia phagocytophila) causes the disease tick-borne fever (TBF) in domestic ruminants and has for decades been one of the main scourges for the sheep industry in the coastal areas of Norway. Current control strategies are based on reduction of tick infestation by chemical acaricides.

Methods

In the present study, we investigated if frequent pour-on applications of pyrethroids would reduce tick infestion rate and seroprevalence of A. phagocytophilum infection in sheep. Forty lambs, one month old, of the Norwegian White Sheep breed were used. The lambs belonged to the experimental sheep flock at the Department of Production Animal Clinical Sciences. None of the lambs had been on I. ricinus infested pasture before turnout (day 0). All lambs were twins and twenty lambs were treated with a pour-on pyrethroid (Bayticol®, Bayer A/S, DK-2300) with a dose of 5 ml on days 0, 14, 28, 42, 56, 70, 84, 98, 112 and 128. Twenty lambs were untreated controls. The lambs were collected every fourteen days on pasture for treatment. In addition, the lambs were examined for ticks, blood sampled, weighed, and rectal temperature was recorded.

Results and conclusion

A significant reduction in tick infestion rate was detected on treated lambs. However, the present results indicate that frequent acaricide treatment does not reduce the seroprevalence to A. phagocytophilum on tick-infested pasture.     

Effect of Bacillus subtilis spore administration on activation of macrophages and natural killer cells in mice

The effect of Bacillus subtilis (strain A102) spores on the activation of murine macrophages and natural killer cells (NK) was examined. The macrophage activity and NK activity were enhanced by oral administration of A102 spores, and slightly enhanced by oral administration of culture supernatant. There was no difference in the results of macrophage activity and NK activity using other live or dead spores. The NK activity and macrophage activity were increased with increments of concentration up to 0.1 g per mouse, and both activities were decreased at concentration of more than 0.15 g per mouse. The NK activity was increased 1 and 2 days after oral administration of A102 spores, and the activity level 2 days after administration was about 3-fold higher than the level prior to treatment. Macrophage activity was also increased from 1 to 3 days after oral administration of A102 spores, and the activity level 3 days after administration was about 3-fold higher than the level prior to treatment. The induction of interferons at 1 day after oral administration in mouse serum was 5-fold higher than that in controls. These findings indicate that oral administration of A102 gave rise to the induction of interferons, and it is likely that macrophages and NK cells were activated by interferons.     

Effect of oral administration of clinically relevant doses of dexamethasone on regulation of cytochrome P450 subfamilies in hepatic microsomes from dogs and rats

OBJECTIVE: To evaluate the effect of oral administration of dexamethasone (DEX) at clinically relevant doses on metabolic activities of cytochrome P450 (CYP) isoenzymes in dogs and rats. ANIMALS: 15 healthy 1-year-old male Beagles and 20 healthy 10-week-old male Wistar rats. PROCEDURE: Hepatic microsomes were harvested from dogs treated orally with DEX at 2.5 and 7.5 mg for 5 days and from rats treated orally with DEX at 0.75, 6, and 48 mg/kg for 5 days. 7-ethoxyresorufin, tolbutamide, bufuralol, and midazolam were used as CYP1A, CYP2C, CYP2D, and CYP3A substrates, respectively. Concentrations of metabolites formed by CYPs were measured by use of high-performance liquid chromatography, except for the resorufin concentrations measured by use of a fluorometric method. Reaction velocity-substrate concentration data were analyzed to obtain maximum reaction velocity (Vmax) and Michaelis-Menten constant (Km). RESULTS: Values of Vmax for midazolam 4-hydroxylation were significantly decreased by treatment with DEX at 2.5 and 7.5 mg in dogs, although values of Km were not affected. Values of Vmax for bufuralol 1'-hydroxylation were also decreased by treatment with DEX. In rats, values of Vmax for midazolam 4- hydroxylation were significantly decreased by treatment with DEX at 0.75 and 6 mg/kg but significantly increased at 48 mg/kg. Other reactions were not affected by treatment with DEX. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that DEX downregulates the CYP3A subfamily when administered at clinically relevant doses to dogs. The effect of downregulation of CYP3A in dogs treated with DEX should be considered to avoid adverse effects from coadministration of drugs.     

RNAi-mediated knockdown of INHBB increases apoptosis and inhibits steroidogenesis in mouse granulosa cells

Inhibins are members of the TGFβ superfamily and act as suppressors of follicle stimulating hormone (FSH) secretion from pituitary glands via a negative feedback mechanism to regulate folliculogenesis. In this study, the INHBB gene was knocked down by three RNAi-Ready pSIREN-RetroQ-ZsGreen vector- mediated recombinant plasmids to explore the effects of INHBB silencing on granulosa cell (GC) cell cycle, apoptosis and steroid production in vitro. Quantitative real-time polymerase chain reaction, Western blot, flow cytometry and ELISA were performed to evaluate the role of INHBB in the mouse GC cell cycle, apoptosis and steroid production in vitro. The results showed that the relative mRNA and protein expression of INHBB in mouse GCs can be significantly reduced by RNAi with pshRNA-B1, pshRNA-B2 and pshRNA-B3 plasmids, with pshRNA-B3 having the best knockdown efficiency. Downregulation of the expression of INHBB significantly arrests cells in the G1 phase of the cell cycle and increases the apoptosis rate in GCs. This was further confirmed by downregulation of the protein expressions of Cyclin D1, Cyclin E and Bcl2, while the protein expression of Bax was upregulated. In addition, specific downregulation of INHBB markedly decreased the concentration of estradiol and progesterone, which was further validated by the decrease in the mRNA levels of CYP19A1and CYP11A1. These findings suggest that inhibin βB is important in the regulation of apoptosis and cell cycle progression in granulosa cells. Furthermore, the inhibin βB subunit has a role in the regulation of steroid hormone biosynthesis. Evidence is accumulating to support the concept that inhibin βB is physiologically essential for early folliculogenesis in the mouse.     

Evaluation of the Subchronic Toxicity of Dietary Administered Equisetum arvense in F344 Rats

Equisetum arvense, commonly known as the field horsetail, has potential as a new functional food ingredient. However, little information is available on its side effects, and the general toxicity of Equisetum arvense has yet to be examined in detail. In the present study, we evaluated the influence of administration in diet at doses of 0, 0.3, 1 and 3% for 13 weeks in male and female F344 rats. No toxicity was detected with reference to clinical signs, body weight, urinalysis, hematology and serum biochemistry data and organ weights. Microscopic examination revealed no histopathological lesions associated with treatment. In conclusion, the no-observed-adverse-effect level (NOAEL) for Equisetum arvense was determined to be greater than 3% in both sexes of F344 rat (males and females: >1.79 g/kg BW/day and >1.85 g/kg BW/day, respectively) under the conditions of the present study.     

胚蛋注射L-精氨酸对蛋雏鸡孵化性能、1~14日龄肠道发育及血清生化指标的影响

本试验旨在研究胚蛋注射L-精氨酸(L-Arg)对蛋雏鸡孵化性能、1~14日龄肠道发育和血清生化指标的影响。选取47周龄京红1号蛋鸡种蛋1080枚,随机分为3组,分别为未注射对照(NC)组、生理盐水注射对照(SC)组和L-Arg注射(Arg)组,每组8个重复,每个重复45枚种蛋。在孵化第17.5天时,Arg组每枚蛋注射0.1 mL 10%的L-Arg溶液(0.85%生理盐水作溶剂,10 mg L-Arg/枚蛋),SC组注射相同剂量的0.85%生理盐水。出壳后,每组选取体重相近的健康母雏120只,随机分为8个重复。试验期14 d。结果表明:1)与NC和SC组相比,胚蛋注射L-Arg对1日龄蛋雏鸡的孵化率和出孵重无显著影响(P>0.05),但显著降低卵黄囊重(P<0.05)。2)与NC和SC组相比,胚蛋注射L-Arg显著提高1日龄蛋雏鸡的空肠长度、3日龄时的十二指肠长度和14日龄时的空肠和回肠长度(P<0.05),对3日龄蛋雏鸡空肠内容物脂肪酶活性有增加趋势(P=0.084)。3)与NC组相比,胚蛋注射L-Arg显著提高14日龄蛋雏鸡的空肠上皮细胞增殖指数(P<0.05)。4)与NC组相比,胚蛋注射L-Arg显著降低3和14日龄蛋雏鸡的血清甘油三酯(TG)含量(P<0.05),显著增加3和14日龄时的血清总胆固醇(TC)和低密度脂蛋白(LDL)含量(P<0.05)。与SC组相比,胚蛋注射L-Arg显著增加14日龄蛋雏鸡的血清高密度脂蛋白(HDL)和葡萄糖(GLU)含量(P<0.05)。由此可见,胚蛋注射10 mg L-Arg对蛋雏鸡的孵化率和出孵重等孵化性能无不良影响;胚蛋注射10 mg L-Arg促进蛋雏鸡的脂质代谢和糖代谢,为早期肠道发育提供更多能量,提高空肠上皮细胞增殖指数,增加肠道长度,促进早期肠道发育。     

Effects of oral administration of furosemide and torsemide in healthy dogs

OBJECTIVE: To investigate the diuretic effects, tolerability, and adverse effects of furosemide and torsemide after short- and long-term administration in healthy dogs. ANIMALS: 8 mixed-breed dogs. PROCEDURES: In a crossover study, furosemide (2 mg/kg), torsemide (0.2 mg/kg), or placebo (bifidobacterium [1 mg/kg]) was administered orally to each dog every 12 hours for 14 days. Blood and urine samples were collected before the study (baseline data) and at intervals on the 1st (short-term administration) and 14th day (long-term administration) of treatment for assessment of urine volume and specific gravity and selected clinicopathologic variables including BUN, creatinine, and aldosterone concentrations, and creatinine clearance. RESULTS: Compared with the baseline value, short-term administration of furosemide or torsemide immediately increased urine volume significantly; after long-term administration of either drug, urine specific gravity decreased significantly. Compared with the effect of placebo, the 24-hour urine volume was significantly increased after short-term administra-tion of furosemide or torsemide. In addition, it was significantly increased after long-term administration of torsemide, compared with that of short-term administration. Long-term administration of furosemide or torsemide increased the BUN and plasma creatinine con-centrations, compared with the baseline value. Compared with the baseline value, plasma aldosterone concentration was significantly increased after long-term administration of either drug and was significantly higher after torsemide treatment than after furosemide treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, diuretic resistance developed after 14 days of furosemide, but not torsemide, administration; however, both loop diuretics were associated with increased BUN and plasma creatinine concentrations, compared with values before treatment.