Correction of organophosphate-induced neuromuscular blockade by diphenhydramine

Dogs exposed to topical organophosphate (fenthion) developed decreased plasma and muscle cholinesterase activities. After 2 doses were applied (1 week between doses), plasma concentrations declined 80% and muscle cholinesterase activity was reduced by 56%. Decremental responses to repetitive nerve stimulation developed after fenthion administration. Diphenhydramine, but not placebo, corrected the electrical abnormalities caused by organophosphate application, but without altering plasma or muscle cholinesterase activity. Control dogs housed in the same kennel demonstrated a slight decrease (18%) of plasma cholinesterase, which indicates that there may be potential cross contamination. Diphenydramine may be effective in treating organophosphate-induced neuromuscular weakness which is refractory to other forms of therapy.     

Anticholinesterase-resistant neuromuscular blockade in sheep given amino-steroid muscle relaxants

Three cases of anticholinesterase-resistant neuromuscular blockade in sheep are described. Neuromuscular blockade produced with pancuronium (n = 2) and vecuronium was only temporarily antagonised with anticholinesterases and signs of residual block-muscular weakness, recumbency, hypoventilation, dyspnoea, dysphagia, 'fade' in evoked responses to repetitive nerve stimulation and rapid exhaustion of cranial nerve reflexes - were observed. Responses to repeated edrophonium and, or neostigmine injections were incomplete and shortlived. These complications probably arose because high loading doses, incremental injections (pancuronium and vecuronium) and infusion (pancuronium) created high plasma drug concentrations at antagonism. This occurred because the facial nerve-levator nasolabialis muscle unit used to monitor drug effects proved resistant to blockade. The effects of relative overdose were probably augmented by the sensitivity of sheep to non-depolarizing neuromuscular blocking agents and the relative insensitivity of monitoring blockade using tactile and visual evaluation of evoked responses.     

Effect of gentamicin administration on the neuromuscular blockade induced by atracurium in cats

Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered as an infusion to 8 anesthetized cats in which neuromuscular blockade was assessed, using the train-of-four response. Once 50% depression of the first-twitch (T1) response was achieved, the infusion was held constant for 60 minutes before being discontinued and the recovery time was determined. The time for recovery was recorded as the time for the train-of-four (T4 ratio) to increase from 50% to 75%. After recovery, atracurium infusion was reinstituted and the cats were again maintained for 60 minutes at 50% depression. A single bolus of gentamicin sulfate (2.0 mg/kg of body weight) was administered IV, and the infusion was continued for another 60 minutes before it was discontinued and the time for recovery was recorded. Within 1 minute of gentamicin administration, the mean +/- SD T1 response decreased from 49 +/- 5% to 33 +/- 8% of baseline and the T4 ratio decreased from 28 +/- 19% to 14 +/- 11%. Peak effect occurred at 5 minutes, with a T1 response of 29 +/- 6% of baseline and a T4 ratio of 13 +/- 12%. By 60 minutes after gentamicin administration, the T1 response had increased to 38 +/- 7% of baseline and the T4 ratio had increased to 21 +/- 13%. The time for recovery significantly (P less than 0.03) increased from 9.9 +/- 3.4 minutes during the control study to 18.1 +/- 10.7 minutes during the gentamicin study. In this study, gentamicin potentiated the neuromuscular blockade induced by atracurium and increased the recovery time. Residual blockade, observed after gentamicin administration was reversed with edrophonium.     

Effects of sevoflurane,propofol or alfaxalone on neuromuscular blockade produced by a single intravenous bolus of rocuronium in dogs

ObjectiveTo compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs.Study designA randomized, prospective, crossover experimental study.AnimalsA total of eight adult Beagle dogs (four female, four male), weighing 8.9–15.3 kg and aged 5–7 years.MethodsThe dogs were anesthetized three times with 1.25× minimum alveolar concentration of sevoflurane (SEVO treatment) and 1.25× minimum infusion rate of propofol (PROP treatment) or alfaxalone (ALFX treatment) at intervals of ≥14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC), a single bolus dose of rocuronium (1 mg kg^–1) was administered intravenously. The times from rocuronium administration to achieving TOF count 0 (onset time), from achieving TOF count 0 to the reappearance of TOF count 4 (clinical blockade period), from 25% to 75% of TOFRC (recovery index) and from achieving TOF count 0 to TOF ratio/TOFRC >0.9 (total neuromuscular blockade duration) were recorded.ResultsThe onset time and recovery index did not differ among the treatments. The median clinical blockade period was longer in the SEVO treatment [27.3 (26.0–30.3) minutes] than in PROP [16.6 (15.4–18.0) minutes; p = 0.002] and ALFX [22.4 (18.6–23.1) minutes; p = 0.017] treatments; and longer in the ALFX treatment than in the PROP treatment (p = 0.020). The mean total neuromuscular blockade duration was longer in the SEVO treatment (43.7 ± 9.9 minutes) than in PROP (25.1 ± 2.7 minutes; p < 0.001) and ALFX (32.5 ± 8.4 minutes; p = 0.036) treatments.Conclusions and clinical relevanceCompared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.     

The post-tetanic count during vecuronium-induced neuromuscular blockade in halothane-anaesthetized dogs

ObjectiveTo evaluate the post‐tetanic count (PTC) for predicting the return of reversible neuromuscular blockade at the n. facialis–m. nasolabialis (nF–mNL) and n. ulnaris–mm. carpi flexorii (nU–mCF) nerve‐muscle units (NMUs) during profound vecuronium neuromuscular blockade in halothane‐anaesthetized dogs.Study designRandomized, prospective, experimental study.AnimalsTwenty‐five dogs (seven male 18 female) undergoing surgery; mean age: 4.8 years; mean body weight 22 kg.MethodsThirty minutes after acepromazine (0.05 mg kg^?1) and morphine (0.5 mg kg^?1) pre‐medication, anaesthesia was induced with intravenous (IV) thiopental and maintained with halothane, N₂O and O₂. The lungs were mechanically ventilated and end‐tidal halothane concentration (Fe′_HAL) maintained at 1.04%. Neuromuscular transmission was monitored using the train‐of‐four count (TOFC) at one nF–mNL and both nU–mCF units. Vecuronium (50 µg kg^?1 IV) was injected after 15 minutes constant Fe′_HAL. When the first twitch (T1) at both nU–mCF units had disappeared (t = 0) one (randomly allocated) ulnar nerve was stimulated every 5 minutes using PTC; TOF stimulation continued at the other sites. The PTC was plotted against the interval between recording time and T1's reappearance at the other NMUs.ResultsAt t = 0, the mean PTC in the contralateral nU–mCF unit was 18 (range 0–20). Mean PTC was a minimum at t = 5, rising to the maximum (20) at 25 minutes. Six dogs were vecuronium‐resistant as monitored by PTC. Excluding data from these revealed a strong negative relationship between ulnar PTC and the time taken for T1's return at the facial (r = ?0.7018; p < 0.00001) and contralateral ulnar (r = ?0.8409; p < 0.00001) NMUs.Conclusion and clinical relevancePost‐tetanic count monitoring beginning >5 minutes after the TOFC at nU–mCF = 0 provided a reliable estimate of T1's return at ulnar and facial NMUs.     

Use of neuromuscular blockade with rocuronium bromide for intubation in cats

ObjectiveTo determine whether neuromuscular blockade with rocuronium bromide (RB) would improve endotracheal intubation (EI) conditions in comparison with topical lidocaine hydrochloride (LH).Study designRandomized prospective study.AnimalsForty seven healthy cats of unspecified breed, aged 17 ± 11 months and weighing 2.8 ± 0.8 kg, undergoing elective procedures.MethodsAnesthesia was induced with xylazine (XZ) (1.1 mg kg^?1 IM) and tiletamine‐zolazepam (XTZ) (7 mg kg^?1 IM) and EI was attempted. Cats which could not be intubated at the first attempt (n = 34), were randomly medicated with either 0.1 mL LH 10% spray on the laryngeal mucosa (n = 17) or 0.6 mg kg^?1 intravenous RB (n = 17). Sixty seconds later, a second attempt at EI was performed. The effect of both drugs was assessed using a previously published scale (Sandor Agoston). EI conditions associated with laryngoscopy, vocal cord position and movement, cough, patient movement, time and attempts needed in order to perform EI were recorded. Heart rate and end‐expired CO₂ concentration were monitored.ResultsGroups were comparable in age, weight, gender and hematological parameters. Clinically acceptable EI conditions were not significantly different between RB and LH assisted groups (p = 0.31). However, there was a significant difference in cough, vocal cord movement and position between the RB and the LH groups. The group intubated at the first attempt and receiving neither RB nor LH coughed persistently (11/13). The cats receiving RB had to be ventilated for 10–28 minutes.Conclusions and clinical relevanceThe present study shows that, when used in cats anesthetized with XTZ, RB paralyzes the internal laryngeal muscles keeping the vocal cords in an intermediate position (paramedial) 60 seconds after being administered. RB is an effective alternative to LH to overcome the airway protective reflexes when performing EI but requires ventilatory support until the paralysis wears off.     

Use of cis-atracurium to maintain moderate neuromuscular blockade in experimental pigs

Objective

To determine the dose of cis-atracurium needed to produce a moderate neuromuscular blockade (NMB) in pigs.

骨碎补水提液对大鼠成骨细胞的影响

为观察骨碎补水提液对体外培养大鼠成骨细胞增殖、分化的影响,用体外培养新生SD大鼠颅盖骨分离的成骨细胞,将不同浓度的骨碎补水提液分别与第3代大鼠成骨细胞进行体外共同培养,采用噻唑蓝(MTT)法测定细胞增殖能力,对硝基苯磷酸盐法(PNPP法)测定细胞的碱性磷酸酶(ALP)活性.结果显示,与对照组相比,作用48 h、72 h,骨碎补水提液均能显著促进大鼠成骨细胞的增殖,且与时效有关;作用48 h ,10-3、10-2 mg/mL骨碎补水提液浓度组可显著升高细胞ALP活性(P<0.05).表明骨碎补水提液中存在较高活性的促大鼠成骨细胞增殖和分化的物质.     

Antagonism of pancuronium neuromuscular blockade in halothane-anesthetized ponies using neostigmine and edrophonium

Efficacy of neostigmine (0.04 mg/kg of body weight) and edrophonium (1 mg/kg), as antagonists for pancuronium neuromuscular blockade in halothane-anesthetized ponies, was evaluated. Neostigmine and edrophonium were satisfactory antagonists, with edrophonium having a significantly (P less than 0.01) more rapid onset of action than did neostigmine. Muscarinic activity of neostigmine and edrophonium was also evaluated. Neither antagonist was administered with atropine. Gastrointestinal effects, increased salivation, and increased airway secretions were minimal with edrophonium, but were marked after neostigmine. Blood pressure increased within 1 to 2 minutes of antagonist administration. Heart rate decreased after edrophonium injection, but this occurred after blood pressure increase. Heart rate increased or did not change after neostigmine administration.     

镉对体外培养大鼠肝细胞自噬的影响

选用体外培养原代大鼠肝细胞为模型,醋酸镉处理之后,用Westernblot和免疫荧光法检测了自噬标记分子LC3的表达水平,在此基础上,利用自噬激活剂（雷帕霉素）诱导自噬水平的升高,用MTT法分析了镉对细胞存活率的影响。结果显示,原代大鼠肝细胞在体外培养过程中自噬水平具有缓慢上升的趋势,而镉处理延缓了这种趋势,降低了自噬的水平和细胞存活率;利用激活剂增强自噬后不能减弱镉的损伤,表明镉有可能通过抑制自噬的保护作用,造成对肝细胞的损伤。     

镉对体外培养大鼠肝细胞DNA甲基化的影响

选用体外培养原代大鼠肝细胞为模型,用醋酸镉进行处理,用免疫荧光法检测了基因组DNA甲基化水平,用偏重亚硫酸氢盐测序法检测了MT、p53和Line1基因的DNA甲基化水平,用qRT-PCR检测了DNMTs基因的mRNA水平。结果显示,原代大鼠肝细胞在体外培养过程中基因组DNA甲基化水平具有缓慢下降的趋势,镉处理加速了这种下降的趋势;但p53、MT和Line1基因的DNA甲基化均未受镉的影响;维持DNA甲基化稳定的DNMTs表达水平受镉的影响呈现下降的趋势。表明镉对肝细胞的损害作用可能是通过降低DNMTs的表达水平,进而破坏基因组DNA甲基化的稳定来完成的;而镉对MT表达水平的影响似乎并非通过DNA甲基化途径来完成,因为在镉处理之前MT的DNA甲基化就已经处在较低的水平。     

Effects of TNF receptor blockade on in vitro cell survival and response to negative energy balance in dairy cattle

Background: Associative data and some controlled studies suggest that the inflammatory cytokine tumor necrosis factor(TNF) α can induce fatty liver in dairy cattle. However, research demonstrating that TNFα is a necessary component in the etiology of bovine fatty liver is lacking. The aim of this work was to evaluate whether blocking TNFα signaling with a synthetic cyclic peptide(TNF receptor loop peptide; TRLP) would improve liver metabolic function and reduce triglyceride accumulation during feed restriction.Results: Capability of TRLP to inhibit TNFα signaling was confirmed on primary bovine hepatocytes treated with recombinant bovine TNFα and 4 doses of TRLP(0, 1, 10, 50 μmol/L) over 24 h. Next, 4 lactating Holstein cows(parity 1.4 ± 0.5, 433 ± 131 d in milk) in an incomplete Latin rectangle design(3 × 2) were subcutaneously administered with different TRLP doses(0, 1.5, 3.0 mg/kg BW) every 4 h for 24 h, followed by an intravenous injection of TNFα(5 μg/kg BW). Before and for 2 h after TNFα injection, TRLP decreased plasma non-esterified fatty acid(NEFA)concentration(P ≤ 0.05), suggesting an altered metabolic response to inflammation. Finally, 10 non-pregnant, nonlactating Holstein cows(3.9 ± 1.1 yr of age) were randomly assigned to treatments: control(carrier: 57% DMSO in PBS)or TRLP(1.75 mg TRLP/kg BW per day). Treatments were administrated every 4 h for 7 d by subcutaneous injection to feed-restricted cows fed 30% of maintenance energy requirements. Daily blood samples were analyzed for glucose,insulin, β-hydroxybutyrate, NEFA, and haptoglobin concentrations, with no treatment effects detected. On d 7, cows completed a glucose tolerance test(GTT) by i.v. administration of a dextrose bolus(300 mg glucose/kg BW). Glucose,insulin, and NEFA responses failed to demonstrate any significant effect of treatment during the GTT. However, plasma and liver analyses were not indicative of dramatic lipolysis or hepatic lipidosis, suggesting that the feed restriction protocol failed to induce the metabolic state of interest. Injection site inflammation, assessed by a scorer blinded to treatment, was enhanced by TRLP compared to control.Conclusions: Although the TRLP inhibited bovine TNFα signaling and altered responses to i.v. administration of TNFα,repeated use over 7 d caused apparent local allergic responses and it failed to alter metabolism during a feed restriction-induced negative energy balance. Although responses to feed restriction seemed atypical in this study, side effects of TRLP argue against its future use as a tool for investigating the role of inflammation in metabolic impacts of negative energy balance.     

Failure to reverse prolonged vecuronium-induced neuromuscular blockade with edrophonium in an anesthetized dog

A case of prolonged muscle relaxation after vecuronium in an anesthetized dog is presented. After using peripheral nerve stimulation to confirm partial recovery of neuromuscular transmission, administration of 0.5 mg/kg IV of intravenous edrophonium failed to complete the reversal process. Subsequent administration of neostigmine resulted in complete recovery from blockade. Without monitoring neuromuscular function with a peripheral nerve stimulator until reversal was complete, it was very likely this patient would have been extubated with incomplete neuromuscular transmission. Several factors affecting the duration of neuromuscular blockade and its reversal are addressed.     

Edrophonium-induced asystole following neuromuscular blockade antagonism in a dog: a case report

Edrophonium was used to antagonise neuromuscular block in a healthy eight-year-old dog following ophthalmic surgery; this caused arrhythmias and asystole lasting 46 sees. The complication probably occurred because of inadequate muscarinic blockade prior to antagonism. The dog made an uneventful recovery.     

Evaluation of neostigmine antagonism at different levels of vecuronium-induced neuromuscular blockade in isoflurane anesthetized dogs

Residual neuromuscular block (NMB) during recovery from general anesthesia may be minimized by antagonizing NMB with neostigmine. We examined neostigmine for restoring neuromuscular function when administered at 2 levels of vecuronium-induced NMB in dogs. Eight healthy adult dogs received vecuronium 0.1 mg/kg body weight (BW), IV, during isoflurane anesthesia. Recovery from vecuronium occurred spontaneously (control group; C), or was enhanced with neostigmine, 0.04 mg/kg BW, IV, administered when 2 (N2) or 4 (N4) responses to train-of-four (TOF) stimulation were first observed. Duration of NMB was significantly shorter for N2 and N4 than for C. The period of complete NMB was equal for all groups; differences were observed during the recovery phase of NMB. Time of neostigmine-enhanced recovery was significantly shorter for N4 than N2, but overall duration of NMB was not reduced. Recovery from NMB was faster with neostigmine. There is no clinical advantage in delaying neostigmine administration once 2 responses to TOF are present.     

A comparison of edrophonium and neostigmine for the reversal of mivacurium-induced neuromuscular blockade in sheep

The rate of reversal of neuromuscular block was compared in 36 sheep receiving either edrophonium (500 μg kg⁻¹) and atropine (80 μg kg⁻¹), neostigmine (50 μg kg⁻¹) and atropine (80 μg kg⁻¹) or saline (10 ml), using the train of four count (TO4C) recorded at n. facialis - m. levator nasolabialis. Neuromuscular block was produced with mivacurium (200 μg kg⁻¹) followed later by a single incremental dose of 70 μg kg⁻¹. Antagonists or saline were given when spontaneous recovery from the incremental dose (T04C = 1) = 1 begun. The T04C increased from 1 to 4 in all animals, in all treatment groups within 10 minutes of reversal. The T04C was 4 in all animals five minutes after edrophonium, and seven minutes after neostigmine; differences were not statistically significant. The T04C was significantly higher with edrophonium two and three minutes after antagonism compared with saline. The data show that spontaneous recovery from mivacurium is rapid in sheep, although reversal is accelerated by anticholinesterase drugs.     

镉对体外培养大鼠大脑皮质神经元钙稳态的影响

选用原代培养大鼠大脑皮质神经元为模型,用神经元特异性烯醇化酶(NSE)抗体经免疫组织化学染色技术鉴定神经元.用不同浓度(0、5、10、20 μmol/L)醋酸镉染毒大鼠大脑皮质神经元12h,利用流式细胞仪检测细胞内[Ca2-]i,ATPase酶试剂盒测定Na-K+ ATPase和Ca2-Mg2--ATPase活性的变化,荧光定量PCR法测定钙调蛋白(CaM) mRNA转录水平.结果表明,免疫组化染色证实培养细胞呈现NSE阳性染色,证明是神经元.与对照组相比,各镉染毒组细胞内[Ca2+]i显著或极显著升高(P＜0.05或P＜0.01),Na--K--ATPase和Ca2+-Mg2+-ATPase活性显著或极显著降低(P＜0.05或P＜0.01),20 μmol/L组CaM mRNA转录水平极显著降低(P＜0.01).说明镉可能通过影响CaM的转录水平与维持钙稳态相关的酶(Na+-K-ATPase和Ca2+-Mg2+-ATPase)活性,干扰神经元细胞内钙稳态,进而造成神经元细胞损伤.     

Effects of thymol and isoeugenol feed supplementation on quail adult performance,egg characteristics and hatching success

1. A study was conducted to evaluate whether feed supplementation with thymol or isoeugenol can alter Japanese quail growth rate and final body weight, the female onset of puberty, hen-day egg production and the physical and chemical characteristics of the egg, as well as its potential to alter hatchability.

2. From 4 to 16 weeks of age, birds from each cage (1 male: 3 females) were assigned to 1 of 3 treatments that differed in the supplement added to the feed: control, thymol or isoeugenol (400?mg/kg). The average ages (d) at first egg lay (FIRST), at 25% egg production (A25% EP), at 50% egg production (A50% EP) and weekly and cumulative hen-day egg production (HDEP) were calculated. In addition, physical and chemical characteristics of the eggs, their fertility and hatchability were also evaluated for each group.

3. Feed supplementation did not significantly affect growth rate, final body weight, egg production parameters, fertility and physical characteristics of egg or most of the fatty acid components of the yolk.

4. The group treated with isoeugenol showed an increase in the percentage of palmitoleic fatty acid compared to the control, with thymol group showing intermediates values.

5. Both thymol and isoeugenol supplemented groups showed increased hatchabilities, by 18·8% and 11·8%, respectively, compared to their control counterparts.

6. The improvement in the hatching success of the eggs from the thymol and isoeugenol supplemented groups without a negative impact on their performance may have important economic implications for future breeding programmes, particularly if these effects generalise from quail to other more commercially important poultry species, such as chickens or turkeys.     

Effects of zeranol on in vitro growth hormone release by lamb and rat pituitary cells

A series of experiments was conducted to evaluate the effect of zeranol on release and synthesis of growth hormone (GH) by anterior pituitary cells established in either static or continuous flow cultures. Young adult male rats, slaughter-age lambs and juvenile lambs were used as sources of pituitary cells. In static primary cell cultures, no consistent effect of zeranol at 10(-7), 10(-9) or 10(-11) M was demonstrated by either rat or ovine cells. Rat pituitaries established in perifusion culture chambers showed no repeatable response to zeranol. Dissociated cells from lambs established in perifusion culture, however, had significant increases in release of GH in response to 37% of zeranol pulse exposures. When dissociated cells from juvenile lamb pituitaries were used, up to 10-fold increases in GH release consistently were measured within minutes of exposure to zeranol.