Upper motor neurone effects in sheep of some beta-carboline alkaloids identified in zygophyllaceous plants

The beta-carbolines harmane, norharmane, tetrahydronorharmane, harmine, harmaline and harmol were administered to sheep to assess their effects on upper motor neurone function. Harmane at a dose rate of 54 mg/kg induced hypomotility, head tremors, pelvic limb paresis, hypermetria and a wide based stance. A range of similar effects were observed with norharmane at the same dose rate. Tetrahydronorharmane at a dose rate of 54 mg/kg induced hypermotility followed by hypomotility, asymmetrical pelvic limb paresis, hypermetria, a wide based stance, and stereotyped eating behaviour. Harmine and harmaline at 6 mg/kg induced mild head and body tremors, and at 18 mg/kg induced hypomotility, intense head and body tremors, pelvic limb paresis, crossing over of limbs, neck extension and head swaying. Harmol was not effective at 54 mg/kg by either the subcutaneous or intraperitoneal routes, but at an intravenous dose of 27 mg/kg it induced hypermotility followed by hypomotility, body tremors, limb paresis, muscle asynergy, a wide based stance and jumping behaviour. Harmane, tetrahydronorharmane, harmaline and harmol were convulsive in some sheep at high dose rates.     

The pathogenesis of the nervous syndrome of Phalaris aquatica toxicity in sheep

The clinical signs displayed by 96 sheep affected by the nervous syndrome of Phalaris aquatica toxicity and 10 normal sheep injected intravenously with the phalaris alkaloid, 5-methoxy dimethyltryptamine (dose range 0.01 to 5.0 mg/kg), were observed. The distributions of phalaris indole-like cytoplasmic pigments in nuclei of the brains and spinal cords of 9 naturally affected sheep were determined microscopically. Based on the relationship between clinical signs and the central nervous system nuclei involved in their production, the distribution of phalaris indole-like pigments, and the pharmacology of dimethylated tryptamines, it is suggested that the nervous syndrome induced by Phalaris aquatica results from a direct action of phalaris alkaloids upon serotonergic receptors in specific brain and spinal cord nuclei.     

The occurrence of Fusarium varieties and their mycotoxins on silo corn. 1. A method for the determination of zearalenone in corn and corn silage by high performance liquid chromatography (HPLC) with fluorescence detection

A method for the determination of zearalenone in maize and maize silage was developed which distinguishes itself by the effective and fast cleaning of the extracts with the help of a silica gel minicolumn. The samples were extracted with chloroform/methanol (9 + 1) and cleaned on a silica gel minicolumn after acid-base partition. The zearalenone was quantitatively determined optionally by means of high-performance liquid chromatography (HPLC) with fluorescence detection (excitation wavelength 236 nm, emission filter 418 nm) or thin-layer chromatography (TLC), p-methoxybenzene diazonium fluoroborate and aluminium chloride were used as detection chemicals. The limits of detection are 0.01 mg/kg (HPLC) and 0.1 mg/kg resp. (TLC), the average recovery is 81%. The method was used for the determination of zearalenone in grain maize, CCM silage and silage from whole maize plants.     

Staggers in sheep associated with the ingestion of Tributes terrestris

The history of an unusual locomotory disturbance of sheep is traced from its first recognition in 1937 through to the most recent outbreak in 1981-83. The condition occurred only at certain times and in restricted areas of the central and northern slopes districts of New South Wales. Outbreaks were repeatedly associated with drought periods during which sheep grazed large areas of Tribulus terrestris for many months at a time. Many thousands of sheep were affected, but the prevalence varied greatly between flocks. The course of the disease was characterised by a slowly developing, irreversible, asymmetrical, weakness of the hindlimbs. The clinical signs suggested that a lesion of the thoraco-lumbar spinal cord region was present. The macroscopic and microscopic examination of the nervous and musculoskeletal systems failed to demonstrate abnormalities which would account for the clinical signs. Haematological, biochemical and toxicological test results supported the concept of a neuromuscular disease process being present, but failed to indicate its aetiology.     

Trypanocidal potentials of Azadirachta indica seeds against Trypanosoma evansi

The trypanocidal potentials of Azadirachta indica seeds methanolic extract (NSME) against Trypanosoma evansi was examined. In vitro studies with the NSME 100mg/ml, 50mg/ml and 25mg/ml immobilized the parasites within 3 min, 8 min and 14 min respectively. In vivo experiments in infected rats at various dosage with NSME expressed transient ability of clearing the parasites in the infected blood. Thin layer chromatographic (TLC) separations of the NSME gave 4 fractions in toluene and ethyl acetate [1:0.25] solvent system on TLC of which only fraction 3 (F3) retained the trypanocidal properties which cleared the parasites in the infected rats for 14 days. The high performance liquid chromatography (HPLC) analysis of NSF F3 revealed the presence of Azadirachtins A and B as active components. The NSF F3 manifested prophylactic potency at a dose of 500 mg/kg/day × 3/7. The packed cell volume (PCV) of the group administered 500 mg/kg/day × 3/7 NSF F3 and normal control (NC) had no significant difference. The NSF F3 also inhibited Phospholipase A(2) enzyme in a dose-dependent pattern.     

Photosensitivity in South Africa. VI. The experimental induction of geeldikkop in sheep with crude steroidal saponins from Tribulus terrestris

Geeldikkop was induced in sheep by the oral administration of crude steroidal saponins from Tribulus terrestris. Two of the sheep developed typical lesions of geeldikkop, including birefringent crystalloid material in bile ducts and concentric periductal lamellar fibrosis. The clinical pathological changes in these sheep were also consistent with those of geeldikkop: aspartate transaminase and gamma-glutamyl transferase activities in the sera of both were elevated, and one had bilirubinaemia. A third sheep became photosensitive without typical lesions of geeldikkop in the liver or changes in the activities of liver enzymes before euthanasia. The findings of these trials are consistent with reports from abroad that ovine hepatogenous photosensitization, caused by Agave lechuguilla and Narthecium ossifragum, can be induced with crude saponins from the respective plants.     

薄层色谱和高效液相色谱联合检测玉米赤霉烯酮的方法研究

建立了薄层色谱法(TLC)定性检测和高效液相色谱法(HPLC)定量检测相结合的检测玉米粉中玉米赤霉烯酮(ZON)的方法。以石油醚∶乙醚∶冰醋酸(70∶28∶2)为展开剂,TCL定性检测ZON,ZON的比移值(Rf值)约为0.26。HPLC对ZON进行定量分析,ZON在0.25~5μg/mL范围内线性关系良好,回收率高,检测限为3μg/kg。试验表明:TLC快速、简便,可作为大批量、快速检测ZON的有效方法;HPLC精确、灵敏度高可作为定量检测ZON的有效手段。     

Photosensitisation and crystal-associated cholangiohepatopathy in sheep grazing Brachiaria decumbens

Two outbreaks of photosensitivity and jaundice in sheep grazing the grass, Brachiaria decumbens. In West Java in 1983 and 1983 and 1990 are described. Aggregates of acicular clefts and crystals were present in bile canaliculi, bile ducts, Kupffer cells, hepatocytes and in kidney tubules. The number of crystals increased with the length of exposure to the plant and sheep that died had the largest accumulations. These crystalline structures have been reported before in this syndrome, but are similar to those seen in Tribulus terrestris and Panicum spp toxicities.     

Experimental evidence that tryptamine alkaloids do not cause Phalaris aquatica sudden death syndrome in sheep

The acute toxicity for sheep of 3 alkaloids that occur in Phalaris acquatica was examined by intravenous and oral administration. The lowest tested dose rates that produced clinically observed signs were, for 5-methoxy dimethyltryptamine, 0.1 mg/kg body weight intravenously and 40 mg/kg orally; for gramine, 10 mg/kg intravenously and 500 mg/kg orally; and for hordenine, 20 mg/kg intravenously and 800 mg/kg orally. All induced the clinical signs observed in the nervous form of phalaris toxicity, but none induced the cardiac, sudden death, syndrome.     

Motor neurone disease in molybdenum-deficient sheep fed the endogenous purine xanthosine: possible mechanism for Tribulus staggers

Background The occurrence of Tribulus terrestris motor neurone disease (MND) in sheep is linked with grazing Tribulus growing on cultivation paddocks. A previous survey found that the molybdenum (Mo) content of Tribulus growing on uncultivated soils in the Coonabarabran district of New South Wales was 3.03 ppm, but on cultivated soils it was <0.04 ppm. Tribulus contains the purine, xanthosine, which functions as a neuromodulator, and the catabolism of xanthosine is Mo‐dependent. Design To investigate the relationship between xanthosine ingestion and low Mo concentration, eight sheep were fed Mo‐deficient lucerne chaff (<0.10 ppm), the Mo antagonist, sodium tungstate, and xanthosine (25 mg/kg/day) over 18 weeks and then returned to pasture. Results Signs of MND developed in two sheep 30 months later and astrocyte degeneration occurred in all sheep. Conclusion The findings were similar to those observed in sheep with T. terrestris MND, suggesting that the combination of xanthosine ingestion and Mo deficiency may be the cause of this disorder.     

Comparative pharmacokinetics of diminazene in lactating goats and sheep

The pharmacokinetic aspects of diminazene aceturate were studied in lactating goats and sheep after single intravenous and intramuscular administrations of 3.5 mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed phase high-performance liquid chromatography (HPLC) after ion-pair extraction. Following intravenous injection, the disposition of diminazene in goats and sheep conformed to a two-compartment model with rapid distribution and slower elimination phases. Values of (t1/2 beta) were obtained indicating a slower final disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h). Diminazene concentrations were maintained for more than 4 days in the plasma of goats and sheep. In both species of animals, diminazene was rapidly absorbed following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half-life (t1/2el) of diminazene after intramuscular administration was shorter in goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of diminazene after intramuscular administration were 94.94% and 82.64% in goats and sheep, respectively. Diminazene could be detected in milk of goats and sheep within 10 min post-injection. Milk concentrations of the drug were lower in goats than in sheep and were detected for 5 and 6 days following both routes of administration, respectively.     

Enhanced Plasma Availability of the Metabolites of Albendazole in Fasted Adult Sheep

Lifschitz, A., Virkel G., Mastromarino, M. and Lanusse C., 1997. Enhanced plasma availability of the metabolites of albendazole in fasted adult sheep. Veterinary Research Communications, 21 (3), 201-211The influence of fasting prior to treatment and of dosing rate on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites was studied in adult sheep grazing on pasture. A micronized suspension of ABZ was administered orally at either 7.5 mg/kg (group A) or 11.3 mg/kg (group C) to sheep fed ad libitum, and at 7.5 mg/kg to sheep subjected to a 24 h fasting period prior to treatment (group B). Blood samples were taken serially over 96 h after treatment, and the plasma was analysed for ABZ and its metabolites by high-performance liquid chromatography. ABZSO and ABZSO2 were recovered from the plasma. Fasting induced marked modifications in the pharmacokinetic behaviour of the ABZ metabolites in sheep. An extended absorption process, with a delayed peak concentration in the plasma, was observed for both metabolites in the fasted sheep. Significantly higher area under the curve (AUC) and peak plasma concentration (Cmax) values were obtained for both metabolites in the fasted animals compared to those fed ad libitum. Delayed elimination with prolonged detection in plasma was also observed in the fasted sheep. Treatment with ABZ at 7.5 mg/kg in the starved animals resulted in bioequivalence to the administration of the compound at a 50% higher dose rate (11.3 mg/kg) in the fed animals. It is suggested that fasting enhances ABZ dissolution and absorption by delaying its passage down the digestive tract.     

A comparison of plasma metabolite levels in goats and sheep during continuous low-level administration of fenbendazole

Plasma levels of fenbendazole (FBZ) and its sulphoxide (OFZ) and sulphone (FBZ.SO₂) metabolites were measured in goats and sheep during low-level administration of FBZ given by intraruminal infusion or formulated into a urea-molasses feed supplement block (UMB). In experiment 1, 6 goats and 6 sheep were offered UMB containing 0.5 g FBZ/kg (MUMB) and individual block consumption was measured daily for 18 days. In experiment 2, some of the same animals (n=4 for each species) received FBZ by intraruminal infusion at 1, 1.5 and 3 mg/kg liveweight per day for 7 days at each dosage. FBZ, OFZ and FBZ.SO levels were determined in plasma collected every 3 days in experiment 1 and on days 4, 5 and²6 of each infusion period in experiment 2. In both experiments, higher equilibrium levels were observed for the three metabolites in sheep than in goats. Significant linear relationships were observed between the daily FBZ dosages and the plasma levels of the three metabolites in both species. The regression coefficients were significantly higher in sheep than in goats for FBZ and OFZ but not for FBZ.SO₂, and they were also significantly higher during MUMB administration than during infusion for all three metabolites in both species. FBZ is a suitable anthelmintic for incorporation into a MUMB formulation for use in livestock production systems where responses to molasses urea supplementation have been demonstrated and gastrointestinal parasitism impairs productivity. The results indicate that target dose rates for goats should be 0.75 mg/kg per day compared with 0.5 mg/kg per day for sheep.Abbreviations ANOVA analysis of variance - FBZ fenbendazole - FBZ.SO₂ fenbendazole sulphone - HPLC high-performance liquid chromatography - MUMB urea-molasses feed supplement block containing 0.5 g fenbendazole/kg - OFZ fenbendazole sulphoxide - UMB urea-molasses feed supplment block     

Effects of tolazoline and yohimbine on xylazine-induced central nervous system depression, bradycardia, and tachypnea in sheep

We compared the ability of tolazoline and yohimbine to antagonize xylazine-induced central nervous system depression, bradycardia, and tachypnea in 9 ewes and 5 rams. Once a week for 3 weeks, each sheep received one IV treatment of 0.4 mg xylazine/kg, 0.4 mg xylazine/kg followed in 10 minutes by 2 mg tolazoline/kg, or 0.4 mg xylazine/kg followed in 10 minutes by 0.2 mg yohimbine/kg. The order of the 3 treatments in each sheep was randomized. Xylazine alone caused recumbency for 41.0 +/- 3.7 minutes (mean +/- SEM). Tolazoline and yohimbine shortened the xylazine-induced recumbency to 12.1 +/- 0.9 minutes and 18.1 +/- 1.5 minutes, respectively. Sheep given xylazine alone had head droop for 34.0 +/- 5.4 minutes after rising. Head drooping of sheep given tolazoline or yohimbine was reduced to 10.1 +/- 1.7 minutes and 14.2 +/- 1.7 minutes, respectively. Both tolazoline and yohimbine reversed the bradycardia and tachypnea that followed xylazine administration. No statistical differences in the rate and magnitude of the reversal were observed between the 2 drugs.     

当归颗粒剂与煎剂有效成分及体外抑菌活性比较

为了比较当归颗粒剂与煎剂在有效成分和药效上的差异,采用薄层色谱法(TLC)鉴定当归颗粒剂;高效液相色谱法(HPLC)测定颗粒剂、煎剂和对照药材中阿魏酸的含量;应用《中药色谱指纹图谱相似度评价》软件对颗粒剂、煎剂进行相似度评价,同时进行体外抑菌试验。结果表明,当归颗粒剂TLC图中存在当归对照药材的特征斑点,与对照药材HPLC特征图谱相似度达95.1%;颗粒剂、煎剂和对照药材中阿魏酸的含量分别为3.95、1.69、2.84mg/g;抑菌结果为金黄色葡萄球菌、沙门菌抑菌圈颗粒剂和煎剂相同,大肠埃希菌、链球菌抑菌圈颗粒剂煎剂。通过试验发现,当归颗粒剂中有效成分与对照药材相近,体外抑菌结果优于煎剂。     

Milk depletion of dicloxacillin residues in cows and sheep following intramammary administration

The excretion rate of dicloxacillin from milk was studied after intramammary administration of a suspension of the drug active in vegetable oil. Eight cows and eight sheep, four of each group in low and four in high milk production, were dosed with 200 mg dicloxacillin/quarter in cows and 100 mg dicloxacillin/quarter in sheep, three times at 12 h intervals. The dicloxacillin concentrations in milk were quantified by high performance liquid chromatography (HPLC). In cows, time until dicloxacillin was undetectable was 48 h and no difference was observed between the groups. In sheep, dicloxacillin was undetectable 72 h and 84 h after the treatment in low and in high milk production groups, respectively. The implications of several factors affecting the possible milk withdrawal period were studied. The results indicated that the pharmaceutical vehicle and the coefficient of lipid solubility exerted major effects on depletion time.     

Comparative pharmacokinetics of febantel and its metabolites in sheep and cattle

The pharmacokinetics of febantel and its main metabolites were studied in cattle and sheep. Seven ewes and 4 heifers were given febantel orally in a single dose of 7.5 mg/kg, 25 mg/kg, or 45 mg/kg of body weight. Plasma concentrations vs time of febantel and individual metabolites were determined by high-performance liquid chromatography analysis. Intestinal absorption of febantel was faster and biotransformations were more active in sheep than in cattle.     

联合应用阿苯达唑和伊维菌素在线虫感染鄂尔多斯细毛羊体内的药动学研究

为阐明联合应用阿苯达唑(ABZ)和伊维菌素(IVM)在胃肠道线虫感染鄂尔多斯细毛羊体内的药动学互作关系,以感染胃肠道线虫的鄂尔多斯细毛羊为研究对象,比较研究了单独或联合应用阿苯达唑和伊维菌素后的药物动力学特征。通过粪便虫卵检查法,选取感染胃肠道线虫的鄂尔多斯细毛羊15只,随机分成3组,每组5只。第1组口服给予阿苯达唑(15mg/kg),第2组皮下注射伊维菌素(0.2mg/kg),第3组皮下注射伊维菌素(0.2mg/kg)的同时口服阿苯达唑(15mg/kg)。于给药后不同时间,由颈静脉采集血样,分离血浆,并用高效液相色谱法测定各时间点血浆阿苯达唑、阿苯达唑亚砜、阿苯达唑砜和伊维菌素浓度,并用PK Solution 2.0药物动力学软件计算出各药动学参数。结果表明,联合用药组绵羊血浆伊维菌素峰浓度(Cmax)、药时曲线下面积(AUC)和平均滞留时间(MRT)分别为44.80ng/mL±6.12ng/mL、5 007.46ng.h/mL±1 301.42ng.h/mL和85.47h±5.03h,均显著(P<0.05)小于单独用药组的对应参数值67.62ng/mL±9.06ng/mL、7 125.08ng.h/mL±908.52ng.h/mL和113.39h±9.00h。口服阿苯达唑组绵羊血浆中仅检测到了阿苯达唑砜和阿苯达唑亚砜,而未检测到阿苯达唑母药。联合用药后,除阿苯达唑砜的达峰时间(T max)显著推迟外,阿苯达唑砜和阿苯达唑亚砜的其他各参数之间均无显著性差异。因此,联合应用IVM和ABZ可影响它们在胃肠道线虫感染鄂尔多斯细毛羊体内的药动学特征,且对伊维菌素药动学特征的影响尤为明显,在临床联合用药过程中应予以重视。     

西藏阿里地区冰川棘豆毒性生物碱的鉴定

光谱分析表明冰川棘豆生物碱结晶Ⅰ为含有1分子结晶水的2,2,6,6-四甲基-4哌啶酮（2,2,6,6-tetramethyl-4-piperidone,TMPD）。小鼠口服LD50为935.4 mg/kg,95％可信限为852.7～1021.4 mg/kg。小鼠TMPD急性中毒症状与山羊冰川棘豆自然中毒症状基本相似。     

Alternative treatment of ovarian cysts with Tribulus terrestris extract: a rat model

Tribulus terrestris has long been used in traditional medicine to treat impotency and improve sexual functions in man. The aim of this study was to evaluate the efficiency of T. terrestris extract in the treatment of polycystic ovary (PCO) in Wistar rat. Estradiol valerate was injected to 15 mature Wistar rats to induce PCO. Rats were randomly divided into three groups (control, low-dose and high-dose groups) of five each and received 0, 5 and 10 mg of T. terrestris extract, respectively.Treatments began on days 50 and 61 after estradiol injection; at the same time, vaginal smear was prepared. The ovaries were removed on day 62, and histological sections were prepared accordingly. The number and diameter of corpora lutea, thickness of the theca interna layer and the number of all follicles were evaluated in both ovaries. In comparison with the control group, the number of corpora lutea and primary and secondary follicles significantly increased following T. terrestris treatment; however, the number of ovarian cysts significantly decreased. It can be concluded that T. terrestris have a luteinizing effect on ovarian cysts, which may relate to its gonadotropin-like activity; also, a high dose of the extract can efficiently remove ovarian cysts and resume ovarian activity.