The Effect of Ivermectin on Convulsions in Rats Produced by Lidocaine and Strychnine

Ivermectin is one of the most commonly used drugs in pharmacotherapy of parasitic diseases in domestic and wild animals caused by parasitic nematodes and arthropods. However, ivermectin and other avermectins very often produce side-effects in hosts. The most dominant clinical symptom of ivermectin toxicity in domestic and wild animals is CNS depression. In nematodes, the target site of ivermectin’s action is glutamate-gated chloride-channel receptor and GABA receptor. The depressive effect of ivermectin in mammals might include more than one mechanism; therefore, the anticonvulsive effect of ivermectin against convulsions caused by lidocaine and strychnine was evaluated. Ivermectin antagonized lidocaine- and strychnine-induced convulsions in rats, although these have different mechanisms. In the present study, the anticonvulsive ED₅₀ of ivermectin for lidocaine-induced convulsions was 2.44 mg/kg (95% CL 1.67 to 3.57 mg/kg), whereas for convulsions induced by strychnine it was higher at 4.25 mg/kg (95% CL 2.32 to 3.78 mg/kg). At the same time, both anticonvulsive doses are significantly lower then the observed LD₅₀ of ivermectin (18.20 mg/kg). Furthermore, flumazenil (0.1 and 0.2 mg/kg), an antagonist of benzodiazepine receptors, antagonizes just one part of these anticonvulsive effects of ivermectin. Our results show the significant anticonvulsive properties of ivermectin and support the findings that ivermectin in the CNS of mammals produces multiple inhibitory effects, probably through participation in the function of GABA-sensitive and GABA-insensitive chloride channels.     

Occurrence of Spontaneous Tumors in the Central Nervous System (CNS) of F344 and SD Rats

In order to accurately assess the carcinogenicity of chemicals with regard to rare tumors such as rat CNS tumors, sufficient information about spontaneous tumors are very important. This paper presents the data on the type, incidence and detected age of CNS tumors in F344/DuCrlCrlj (a total of 1363 males and 1363 females) and Crl:CD(SD) rats (a total of 1650 males and 1705 females) collected from in-house background data-collection studies and control groups of carcinogenicity studies at our laboratory, together with those previously reported in F344 and SD rats. The present data on F344/DuCrlCrlj rats (F344 rats) and Crl:CD(SD) rats (SD rats) clarified the following. (1) The incidences of all CNS tumors observed in F344 rats were less than 1%. (2) The incidences of malignant astrocytoma and granular cell tumor were higher in male SD rats than in female SD rats. (3) The incidences of astrocytoma and granular cell tumor were higher in SD rats than in F344 rats. (4) Among astrocytoma, oligodendroglioma and granular cell tumor, oligodendroglioma was detected at the youngest age, followed by astrocytoma, and ultimately, granular cell tumor developed in both strains. The incidences observed in our study were almost consistent with those previously reported in F344 and SD rats.     

阿维菌素微囊对大鼠急性和亚慢性毒性试验

探讨阿维菌素微囊的安全性,为临床研究提供试验依据,以大鼠作为研究对象,采用腹腔注射法进行了急性和亚慢性毒性试验。结果表明,阿维菌素微囊的半数致死量(LD50)为31.73 mg/kg,与普通注射剂相比大了113%;再以1/10、1/20和1/50 LD50(高、中、低剂量组)给大鼠用药,连续腹腔注射21 d,给药部位未见异常,低剂量组血液生理生化指标正常,各实质性器官细胞未见组织学病变;高、中剂量组出现体重增长缓慢、行动迟缓等异常情况,停药2周后恢复正常。说明阿维菌素经微囊化后毒性明显降低,该制剂基本安全,可用于临床研究。     

叶酸对铅中毒幼年大鼠中枢神经系统的保护作用

通过研究铅对大鼠中枢神经元的损伤以及应用叶酸后的影响,探讨了叶酸对铅中毒条件下中枢神经元的保护作用。将健康清洁级初断乳3周龄SD大鼠随机分为铅染毒组,叶酸给药组及生理盐水组。各组于处理后第2、3、4周取材。铅染毒组、叶酸给药组每组各30只,生理盐水组12只,共72只。测量血铅,分别进行海马和小脑组织的H—E染色及凋亡抑制基因Bcl—2、凋亡基因Bax的蛋白免疫电泳,并作光密度分析。结果,通过对各个时间段各组血铅测定,可得叶酸给药组血铅含量低于铅染毒组。铅染毒组Bcl-2蛋白表达量少于给药组,而Bax多于给药组,H—E染色结果铅染毒组神经细胞数量明显少于叶酸给药组。结果表明,叶酸可降低铅中毒大鼠的血铅浓度,并具有一定抗细胞损伤作用,对铅中毒大鼠的中枢神经元具有一定的保护作用。     

复方当归制剂对慢性氟中毒大鼠抗氧化系统的影响

采用Wistar大鼠复制慢性氟中毒模型,口服不同剂量的复方当归制剂,探讨其对慢性氟中毒大鼠的颉颃作用机理。检测各组大鼠血浆超氧化物歧化酶和谷胱甘肽过氧化物酶活性以及丙二醛(MDA)含量。实验结束时,测定血浆和肝、肾组织中的上述各项指标及机体总抗氧化力。结果表明,慢性氟中毒大鼠肾脏的脂质过氧化损伤最为明显,其抗氧化酶活力显著下降,脂质过氧化产物血浆MDA含量明显升高。灌服一定剂量的复方当归制剂能缓解氟中毒大鼠牙齿损伤程度,推迟氟斑牙的发生时间,还能明显增强机体总抗氧化力。     

芦丁对大鼠免疫器官指数的影响

研究天然植物提取物芦丁对大鼠免疫器官指数的影响,考察芦丁调节动物免疫功能的作用.选择16只Wistar雌性青春期大鼠,随机分为2组,每组8只,分别为对照组(每日每只灌胃生理盐水2 mL)、芦丁组(每日灌服芦丁60 mg/kg体重),正式试验为期2周.12只Wistar受孕母鼠,随机分为2组,每组6只,相同处理,从哺乳第...     

Magnetic resonance imaging of a brain abscess in a 10-month-old filly

The purpose of this paper was to correlate the magnetic resonance imaging (MRI) characteristics of a mature brain abscess in a horse with histopathologic alterations of brain tissue. Eight months after the onset of clinical signs, MRI of the brain of a 10-month-old filly was performed. A large space-occupying lesion in the right cerebral hemisphere was identified. This space-occupying lesion was delineated by a thick and well-defined capsule that was isointense to brain parenchyma on the T1-weighted images and with a markedly hypointense on the T2-weighted images. The identification of such a capsule is highly diagnostic of a mature brain abscess. The lesion seen on MR images was confirmed at necropsy where a large abscess of the right hemisphere was observed. Streptococcus zooepidemicus and Pseudomonas aeruginosa were isolated from the abscess. Based on histopathologic examination, the signal characteristics of the capsule on T1-weighted and T2-weighted images were found to be due to the presence of numerous hemosiderin-laden macrophages. These results are in agreement with previous studies on human patients. This report confirms the value of MRI in the diagnosis of equine brain diseases.     

Pharmacokinetics of acyclovir in adult horses

Objective: To determine the pharmacokinetics of acyclovir administered intravenously (IV) and orally to healthy adult horses. Design: Random cross‐over with an approximate 1‐week washout period between trials. Setting: University veterinary medical teaching hospital. Animals: Six healthy adult research herd horses. Interventions and main results: Acyclovir was administered IV (10 mg/kg in 1 L isotonic crystalloid solution over 60 minutes) and orally (20 mg/kg) to healthy adult horses. Plasma samples were obtained and acyclovir concentrations were determined by high‐pressure liquid chromatography. Peak concentration (mean±SD) for IV acyclovir was 13.74±5.88 μg/mL at the completion of the 1‐hour infusion. The half‐life of the distribution phase (α) was 0.16 hours while the half‐life of the elimination phase (β) was 9.6 hours. The steady‐state volume of distribution was 3.93±1.21 L/kg. We were unable to measure pharmacokinetics after PO acyclovir as plasma concentrations were below the lower limits of detection in all 6 horses. Conclusions: IV administration of acyclovir to healthy adult horses achieves concentrations within the sensitivity range described for equine herpes virus‐type 1. The oral bioavailability of acyclovir in horses is low and additional studies are required.     

Case of suspected theobromine poisoning in dairy cattle

High-yielding dairy cows collapsed and died displaying signs of a disturbed central nervous system (muscle tremor, convulsion) and a considerably reduced body condition score. An intense diagnostic screening did not allow to confirm a definite diagnosis. Therefore, further analyses including an evaluation of feeds and feeding were initiated. The herd was fed a total mixed ration (TMR) based on corn and grass silage of moderate nutritive value supplemented with various amounts of chocolate chips. In retrospect, the amount of chocolate chips added to the respective TMR batches could not be quantified. These chips were purchased from a company producing bakery and chocolate products for human consumption and added to the silage and therefore to the TMR in order to increase the energy intake of the animals. Because the TMR, which was fed during the time of the incidence, was no longer available, a sample of a later batch of silage was examined. The amount of chocolate chips was quantified (0.44% per fresh matter), and a theobromine analysis was performed in the chocolate chips of the available batch (69.7 mg/100 g fresh matter). Because of the possible link between chocolate intake and observed signs, an immediate cessation of using the chocolate chips was recommended in addition to an optimisation of the TMR, that is an increase of the energy density. Even though the theobromine intake during the time of the incidence is unknown and information about toxicity of theobromine in ruminants is limited, we suspect that the feeding of chocolate in this case caused all signs including the sudden death of the cows. Further reasons are that no differential diagnoses were established and the problems at the farm stopped after removing the chocolate from the TMR.     

纯化的大豆凝集素对大鼠内脏器官发育与免疫功能的影响

试验的目的是研究日粮中不同水平的大豆凝集素(SBA)对大鼠免疫功能的影响。选取30只19日龄断奶的SD雄性大鼠,随机分配到5个日粮处理组中。5个处理组大鼠均采食以玉米淀粉酪蛋白为基础的日粮,每只大鼠均供给7g/d日粮和充足清水,试验进行20d。试验中大鼠的平均初始体重为(77.8±2.6)g,5个处理组的日粮SBA水平分别为0(对照组)、0.5、1.0、1.5mg/g和2.0mg/g。结果表明:日粮中添加SBA,大鼠日增重下降(P<0.01),淋巴细胞刺激指数和细胞因子浓度均下降(P<0.05),另外血浆免疫球蛋白水平也明显下降(P<0.05)。表明日粮添加纯化SBA能够影响大鼠生长性能,并能够影响大鼠的细胞免疫功能和体液免疫功能。     

MRI features of CNS lymphoma in dogs and cats

The magnetic resonance (MR) imaging features of central nervous system lymphoma in eight dogs and four cats are described. Intracranial lesions affected the rostrotentorial structures in six dogs and caudotentorial structures in two cats. Lesions affected the spinal cord in two dogs and in two cats. One dog and one cat with intracranial lymphoma had signs of local extracranial extension and lymphadenopathy. Lesions were considered extraparenchymal in four dogs and three cats, intraparenchymal in two dogs and one cat, and appeared to have both intra- and extraparenchymal components in two dogs. All lesions were hyperintense in T2-weighted images when compared to white matter, most were hypointense in T1-weighted images (7/12), and most were hyperintense in fluid-attenuated inversion recovery (FLAIR) images (5/9). When compared to grey matter, these lesions appear either isointense (5/12) or hyperintense (7/12) on T2-weighted images, half of them were hypointense in T1-weighted images (6/12), and most were isointense in FLAIR images (7/9). Lesion margins were usually indistinct in T2-weighted images (10/12) and had perilesional hyperintensity in FLAIR images (7/9). The majority of lesions (10/12) had abnormal meninges around the lesion and half (6/12) had generalized contrast enhancement. Mass effect was evident in all lesions. Although not specific, when combined with the history and neurologic signs, MR features aid presumptive diagnosis that should be confirmed by cytology or histopathology.     

MRI characteristics of ventral vertebral venous plexus occlusion due to lymphoma in a large breed dog

Intravascular lymphoma is a rare presentation of lymphoma with a predilection to the central nervous system (CNS). A 9-year-old male-neutered Collie presented with a 3-month history of lymphadenopathy and a 6-day history of an acute onset, progressive, painful, symmetrical L4-S3 myelopathy. Magnetic resonance imaging revealed multifocal extradural spinal cord compressions from L3 to L6 secondary to a bilaterally enlarged and occluded ventral vertebral venous plexus (VVVP). Histopathology revealed low-grade lymphoma within the venous plexus in the lumbar vertebral column, tracheobronchial lymph nodes, and tonsils. Intravascular lymphoma should be considered a differential diagnosis for enlarged VVVP causing compression of the spinal cord.     

褪黑素对LPS致大鼠海马炎性损伤的保护作用

本研究旨在探究褪黑素（MT）对脂多糖（LPS）致大鼠海马炎性损伤的保护作用。选取40只4周龄健康雄性SD大鼠,随机分为4组：空白组（CON组）、模型组（LPS组）、褪黑素干预组（LPS+MT组）及褪黑素组（MT组）。通过腹腔注射的方式给予大鼠10 mg·kg^-1MT和/或10 mg·kg^-1LPS,4 h后,采用旷场试验对各组大鼠进行行为学测试;试验结束称大鼠体重,解剖取海马称重并计算海马体系数;苏木精-伊红（HE）染色观察脑切片中海马区域病理变化;RT-PCR技术检测海马中小胶质细胞激活标记物Iba-1和CD11b mRNA表达;Western blot法检测海马中炎性因子IL-1β、TNF-α、IL-6、IL-10及TGF-β蛋白表达。结果表明,与CON组相比,LPS组大鼠自主探索行为减少、运动能力下降,海马组织神经细胞排列松散、细胞间隙增大、胞质固缩深染、胶质细胞浸润,小胶质细胞激活标志物Iba-1和CD11b mRNA表达极显著升高（P<0.01）,促炎因子IL-1β、TNF-α及IL-6蛋白表达极显著升高（P<0.01）,抗炎因子IL-10和TGF-β蛋白表达极显著降低（P<0.01）。而与LPS组相比,LPS+MT组大鼠自主探索行为增加、运动能力增强,海马组织神经细胞排列紧密,未见明显病变,小胶质细胞激活标记物Iba-1和CD11b mRNA表达极显著降低（P<0.01）,促炎因子IL-1β、TNF-α及IL-6蛋白表达极显著降低（P<0.01）,抗炎因子IL-10和TGF-β蛋白表达极显著增加（P<0.01）。此外,MT组与CON组相比,所有指标差异均不显著（P>0.05）。结果提示,MT可抑制小胶质细胞激活,减轻海马炎症反应,从而改善LPS造成的大鼠海马炎性损伤。