液相色谱-串联质谱法测定猪尿液中地西泮及其7种代谢物残留

为建立快速测定猪尿中地西泮及其7种代谢物残留的超高效液相色谱-串联质谱(UPLC-MS/MS)确证方法,本研究优化了样品净化的阳离子交换固相萃取柱(PCX柱)及其淋洗洗脱条件.猪尿液酸化后直接经PCX柱净化,依次用水、60％ 甲醇水溶液淋洗,最后用5％ 氨化甲醇洗脱;选用BEH C18色谱柱分离,UPLC-MS/MS进...     

Possible Anxiolytic Effects of Ivermectin in Rats

Ivermectin, a mixture of 22,23-dihydroavermectin B_1a (80%) and B_1b (20%), is produced by Streptomyces avermectilis, an actinomycete. It is a macrocyclic lactone disaccharide, a member of the avermectin family, and is used as an antiparasitic drug. Previous studies performed in our laboratory showed that doramectin, another avermectin drug, interferes with GABAergic-related behaviours, leading to anxiety and seizures. The objective of the present study was to examine the effects of ivermectin (0.5 and 1.0 mg/kg) on the central nervous system of rats, using behavioural models related to GABAergic neurotransmission. A known anxiolytic drug, diazepam, was used as a positive control. Open field and elevated plus-maze behaviours, as well as conflict behaviour to a conditioned response, were assessed. The effects of ivermectin and diazepam in reversing the anxiety induced by picrotoxin was studied. The protective effects of ivermectin on pentylenetetrazole- and picrotoxin-induced seizures were also investigated. In the open field, 1.0 mg/kg ivermectin decreased locomotion frequency at 15 and 60 min of observation, rearing behaviour showed a biphasic effect at 15 and 30 min and duration of immobility was increased in all sessions after 1.0 mg/kg ivermectin. These data suggest anxiolytic or sedative effects. Ivermectin and diazepam both had a tendency to cause an increase both in the number of entries into the open arms and on the time spent in the open arms of an elevated plus-maze. Picrotoxin on its own reduced the number of entries as well as the time spent in the open arms. Both diazepam and ivermectin reversed these effects of picrotoxin. In conflict behaviour analysis, ivermectin and diazepam gave the classic effect of an anxiolytic drug, reversing the conditioned response to shock. Ivermectin protected rats from the convulsant effects of pentylenetetrazole but not from those of picrotoxin. Thus, ivermectin had the pharmacological profile of an anxiolytic drug with GABAergic properties. The lack of effect on seizures induced by picrotoxin suggests that the action of ivermectin is different from that of the benzodiazepine drugs.     

安定在碳糊电极上的电化学特性

在０．０５０ｍｏｌ／Ｌ ＨＣｌ和０．０１５ｍｏｌ／Ｌ ＫＮＯ３溶液中，安定在碳糊是极上于－０．７７Ｖ左右产生一灵敏的吸附阴极溶出伏安峰。线性范畴为１．０×１０＾－７￣４．０×１０＾－５ｍｏｌ／Ｌ，检测下限为５．０×１０＾－８ｍｏｌ／Ｌ，测定了血清中的安定含量，结果满意，循环伏安实验结果证实安定在碳糊电极上的吸附为反应物吸附。     

Acute Hepatic Necrosis And Liver Failure Associated With Benzodiazepine Therapy In Six Cats, 1986–1995.

A retrospective analysis was conducted of all feline necropsies performed during a nine year period to identify cases of sever, acute, centrilobular (periacinar), hepatic necrosis (ACHN). After exclusion of cats with anemia, a series of seven cases of ACHN was identified. In addition, two similar cases were identified from tissue submitted for histopathology following, and eight had bile duct hyperplasia. Seven of the nine cats received diazepam prior to dath, and one received zolazepam. Of the seven cats that received diazepam, five were healthy prior to treatment and received oral diazepam for the treatment of inappropriate urination, intercat aggression, or skin disease. Two cats which received diazepam exhibited other clinical signs: one had chronic vomiting, and the other received diazepam after biochemical evidence of hepatocellular necrosis was present. Onset of clinical sings in cats receiving oral diazepam occurred 7–13 days following the initiation of treatment. Clinical signs and clinical biochemical analysis were compatible with severe hepatocellular necrosis and acute liver failure. All cats had lesions in other organs: five had pancreatic disease, five had cardiac disease, and five had renal disease. All cats died, or were euthanized, within 4 dyas of the onset of clinical signs and 2 days after presentation to a veterinarian. Fatal, acute, centrilobular hepatic necrosis appears to be a serious adverse reaction to diazepam therapy in certain cats.     

The effects of ketamine hydrochloride and diazepam on the intraocular pressure and pupil diameter of the dog’s eye

Objective To determine the effects of 10% ketamine hydrochloride and 0.5% diazepam on intraocular pressure (IOP) and horizontal pupil diameter (HPD) in the canine eye. Procedures Ten healthy dogs for each treatment group were used in this study. In the first group, 20 mg/kg ketamine hydrochloride was injected intravenously; in the second, 0.5 mg/kg diazepam was similarly injected; and in the third, a control group, 0.9% saline was used. In all groups, IOP and HPD were measured every 5 min for 35 min in the first group, and 60 min in the second and third group. Results A maximum increase in IOP was obtained 5 min after ketamine injection, with IOP of 23.2 ± 5.8 mmHg (a 45.0% increase compared to baseline) in the right eye and 22.9 ± 5.9 mmHg (a 43.5% increase) in the left eye (both significant at P < 0.01). A significant IOP increase was observed throughout the research period of 35 min. Statistically significant increases in HPD (P < 0.05) were observed only at 5 and 25 min after ketamine injection. A significant increase in IOP was obtained 10 min after diazepam injection, showing a maximum IOP 20 ± 5.0 mmHg in the right eye (9.3% increase) and 19.9 ± 5.1 mmHg (8.7% increase) in the left eye (both significant at P < 0.05). HPD decreased during the study period, reaching the lowest level 30 min post‐treatment. Conclusions This study showed a substantial increase in IOP after ketamine injection and a less substantial, but still significant increase after diazepam injection. These findings should be taken into consideration when using these drugs in dogs with fragile corneas, or in dogs predisposed or affected by glaucoma.     

液相色谱串联质谱法测定猪肉中的安定残留

建立了猪肌肉中安定的高效液相色谱-串联质谱检测方法。用乙腈提取猪肌肉组织中的药物,经HLB固相柱净化,采用正电喷雾离子源,在多反应监测(MRM)模式下测定,三对定性离子对(m/z)分别为:285.4>154.0、285.4>193.0和285.4>257.0,定量离子对m/z为285.4>154.0。结果表明:安定在0.1~100 ng/mL内线性良好,相关系数r为0.998 5。在0.5、2、10μg/kg添加水平下,加标回收率为68.2%~97.6%,变异系数(CV)在2.2%~7.8%之间,检测限为0.1μg/kg,定量限为0.5μg/kg。     

欣普贝生与地西泮联合用于足月引产5O例临床观察

目的探讨欣普贝生联合地西泮静脉推注用于足月妊娠引产的临床效果及母婴安全性。方法采用随机对照前瞻性研究方法,对正常单胎头位初产妇足月妊娠。宫颈评分小于6分,无瘢痕子宫,具有引产指征而无使用前列腺素禁忌症的孕妇100例,随机分成观察组50例和对照组50例,观察组阴道放人欣普贝生,有不规律宫缩时静推地西泮10mg,对照组阴道放人欣普贝生,用药12h观察用药前后宫颈Bishop评分变化及用药至分娩时问、阴道分娩率、剖宫产率、总产程、产后24h出血量和新生儿体重、Apgar评分及出现子宫过度刺激等情况的差异。结果观察组用药促宫颈成熟有效率（98％）明显高于对照组（72％）（P〈0．05）;观察组总产程平均为468min,阴道分娩成功率占82％,对照组总产程平均648min,阴道分娩成功率66％,两组差异有显著性（P〈0．05）;产后出血量、新生儿Apgar评分、新生儿体重两组差异无显著性。结论欣普贝生联合应用地西泮对足月妊娠引产安全有效。     

安定对动物抗环境热和冷应激能力的影响

用灌胃法给予小鼠安定2.5、12.5、25.0mg/kg后,在热应激(45±1℃)和冷应激(-5±1℃)条件下,给予安定2.5 mg/kg的给药应激组小鼠的存活时间与应激对照组无差别;而12.5、25.0 mg/kg的给药应激组的存活时间与应激对照组比较,热应激小鼠存活时间延长,而冷应激小鼠的存活时间缩短。安定(12.5 mg/kg)可明显抑制热(38±1℃)应激10min和冷(-5±1℃)应激5min条件下小鼠血浆皮质酮的升高,而当热应激(38±1℃)时间延长至60min,冷应激(-5±1℃)延长至30min时,安定对应激导致的小鼠血浆皮质酮升高则无作用。安定(12.5mg/kg)对热(38±1℃)应激60min引起的小鼠皮质醛固酮、甲状腺素T_4的变化也无明显影响。在热(38±1℃)应激30min的条件下,肌肉注射安定10mg/kg的给药应激组大鼠,血清肌酐,脲氮、谷草转氨酶(SGOT)、谷丙转氨酶(SGPT)明显升高,而应激对照组仅有血清肌酐,SGOT的升高。总之,安定对动物抗环境热和冷应激能力无明显影响。     

The effect of four anesthetic protocols on splenic size in dogs

Objective To characterize the effects of four anesthetic protocols on the size of the spleen during surgery in dogs. Study design Prospective experimental trial. Animals Twenty‐four beagle dogs, 1.1 ± 0.3 years of age and weighing 10.9 ± 2.7 kg. Methods Dogs were allocated to receive one of four anesthetic protocols: 1 – pre‐medication with acepromazine and butorphanol, induction with thiopental; 2 – pre‐medication with acepromazine and butorphanol, induction with propofol; 3 – pre‐medication with medetomidine and butorphanol, induction with propofol; and 4 – pre‐medication with medetomidine and butorphanol, induction with ketamine and diazepam. Anesthesia was then maintained with halothane. At laparotomy, the spleen length, width, and height were measured, these were measured again just prior to closure of the abdomen. Splenic area and volume were calculated. Hematocrit and total serum protein (TSP) were measured before and after induction and during laparotomy. Results Splenic volume was greatest after protocol 4 (161.2 ± 40.2 cm³; p < 0.05) and was least after protocol 2. The differences in volume were because of differences in length, width, and height between groups. There was no significant change in area, length, or width over the study period. Hematocrit decreased significantly in all dogs but at different times. The decrease occurred after pre‐medication if acepromazine was administered, at induction following protocol 3 and during surgery following protocol 4. Conclusions If splenic volume is to be minimized during surgery, then acepromazine and propofol should be used in the anesthetic protocol. The administration of medetomidine, diazepam, and ketamine will produce a greater splenic volume. Lack of correlation between hematocrit and spleen size following the anesthetic protocols studied suggests sequestration of red blood cells in nonsplenic sites.     

Acute pulmonary edema after diazepam-ketamine in a dog

An 8-year-old mixed-breed dog was anesthetized for colonoscopy. Moderate sedation was produced by premedication with glycopyrrolate, acepromazine, and hydromorphone, and anesthesia was induced by IV injection of diazepam and ketamine. Frothy, reddish-colored fluid flowed from the endotracheal tube immediately after endotracheal intubation but ceased after several minutes. Furosemide was injected IV. Anesthesia was maintained by sevoflurane in oxygen. Ventilation and arterial blood pressure were satisfactory, however, after oxygen was administered to maintain normal hemoglobin saturation. Radiography revealed changes consistent with a diagnosis of pulmonary edema. The following day, ventricular premature contractions developed and atrial dissociation, valvular regurgitation, and pulmonary hypertension were diagnosed on echocardiography. The proposed etiology is either profound transient hypotension and/or pulmonary hypertension induced by ketamine. The cardiac abnormalities that were present the following day suggest that myocardial dysfunction after induction of anesthesia was more severe than was apparent as assessed by routine physical examination and monitoring methods.