The use of combined xylazine and lignocaine epidural injection in ewes with vaginal or uterine prolapses

Two millilitres of solution calculated to contain 0.07 mg/kg xylazine and 0.5 mg/kg lignocaine injected at the sacrococcygeal epidural site provided caudal analgesia within 2 min in 61 sheep. This analgesic protocol eliminated forceful abdominal straining behavior following replacement of vaginal prolapse for at least 24 h in 48 of 52 ewes (92%) and in all 9 ewes with uterine prolapse. Moderate pelvic limb ataxia was observed in 25 sheep (41%) for up to 24 h after epidural injection. Sedation was noted in one ewe but no other systemic effects of xylazine injection, such as excessive salivation or ruminal distension, were observed. No long-term adverse reactions to xylazine injection were noted. The combined epidural injection regimen of xylazine and lignocaine is recommended as an adjunct for pain relief and control of abdominal straining following replacement of vaginal and uterine prolapse in ewes.     

Assessment of xylazine hydrochloride epidural analgesia for open castration of rams

Epidural xylazine injected at the sacrococcygeal site 40 to 150 min prior to surgery (at a dose of 0.05 to 0.10 mg/kg) provided good analgesia during scrotal skin incision in all 20 experimental rams but in only 10 rams (50%) at incision and separation of tunica vaginalis, and 6 rams (30%) during ligation of the spermatic cord. There was a significant correlation between the decrease in heart rate and the dosage of epidural xylazine. Heart rate increased significantly during incision of the tunics and spermatic cord ligation but was not significantly correlated to the clinical assessment of analgesia. There was no significant correlation between the presence of surgical analgesia and the dosage of epidural xylazine: Pelvic limb ataxia was still evident in 12 rams (60%) at 8 h after epidural xylazine injection. Epidural xylazine provided good somatic analgesia during open castration of 20 rams but visceral analgesia was unpredictable. Factors in addition to the dosage of sacrococcygeal epidural xylazine affects the degree of surgical analgesia obtained for open castration of rams.     

Evaluation of a combination of tiletamine and zolazepam as an anesthetic for ferrets

A combination of equal parts by weight of tiletamine hyrochloride and zolazepam hydrochloride was evaluated clinically in 12 adult male ferrets. Two dosage levels of 12 mg/kg and 22 mg/kg were evaluated. Both doses produced excellent immobilization, the length of which was dose dependent. However, only the higher dose consistently produced good muscle relaxation. Excessive pain upon infection was not noted nor was residual lameness evident. Electrocardiagraphically, notching of the QRS complex was noted at both doses. Anesthesia with poor analgesia occurred at the lower dose, while ferrets receiving the higher dose showed more variability in the degree of analgesia. It was concluded that this combination administered intramuscularly provided excellent immobilization, variable muscle relaxation and a generally smooth induction and recovery. At the higher dose, analgesia was adequate for minor surgical procedures of short duration.     

Long term backache after childbirth: prospective search for causative factors.

OBJECTIVES--To assess in a prospective randomised study the association between motor block resulting from high and low dose epidural infusions of bupivacaine in labour and the incidence of long term backache after childbirth, and to compare the incidence of backache in women not receiving epidural analgesia. DESIGN--Women requesting epidural analgesia in labour between October 1991 and March 1994 were randomised to receive infusions of either bupivacaine alone or low dose bupivacaine with opioid. Data were collected during labour and the immediate postpartum period from these women and from women recruited at random over the same time from those who had laboured without epidural analgesia. A postal questionnaire about symptoms was sent three months after childbirth to all women. Further data were collected one year after childbirth from those who had reported new backache at three months. SETTING--St Thomas''s Hospital, London. SUBJECTS--599 women were recruited, of whom 450 (75%) replied to a follow up questionnaire. RESULTS--152 women (33.8% of responders) reported backache lasting three months after delivery and, of these, 33 (7.3%) had not previously suffered with backache. There were no significant differences between the treatment groups in the incidence of postnatal backache overall or of new backache or any symptoms after childbirth. Among all demographic, obstetric, and epidural variables examined the only factors significantly associated with backache after childbirth were backache before and during pregnancy. CONCLUSIONS--The incidence of new long term backache was not significantly increased in women who received epidural analgesia in labour. Motor block resulting from epidural local anaesthetic administration was not a significant factor in the development of backache.     

Epidural Analgesia in Dogs with Special Reference to the Intraarterial Blood Pressure

In order to investigate whether epidural analgesia in dogs employing mepivacaine chloride gives rise to complications, mainly changes in blood pressure, such analgesia was carried out in 35 dogs brought to the clinic for orthopedic, abdominal or perineal operations. Intra-arterial blood pressure measurements were made in 16 dogs. Three different solutions of mepivacaine chloride were used: 1 % solution with adrenaline 1:200,000; 2% solution with adrenaline 1:100,000 and 2% solution with adrenaline 1:200,000. The various solutions showed no significant difference in analgesic effect. Nor was any blood pressure change found during the epidural blockade. As a solution with a higher concentration causes a higher blood level of the analgesic and also greater toxic effects it is recommended that first preference be given to use of a 1 % solution with adrenaline 1:200,000; second choice is a 2 % solution with adrenaline 1:200,000 and third choice the 2 % solution with adrenaline 1:100,000.     

Effects of epidural administration of xylazine or lidocaine on bovine uterine motility and perineal analgesia

The objective of this study was to evaluate and compare the effects of caudal epidural (sacral-coccygeal interspace) administration of xylazine or lidocaine on uterine motility and perineal analgesia in the cow. Six Holstein cows (7 d post estrus) were assigned to one of three treatment groups: control (5 ml saline); lidocaine (0.2 mg/kg, 2% solution); and xylazine (0.06 mg/kg suspended in 5 ml saline), with each cow randomly assigned to each treatment over a period of three estrous cycles. Uterine motility, perineal analgesia, electrocardiography, and overt signs of sedation were recorded. Data were collected at 10-min intervals starting 10 min before treatment and continuing until 60 min post treatment. At 60 min post treatment, oxytocin (20 USP units) was administered i.v. to serve as a positive control for uterine motility. In the xylazine group, uterine motility significantly (P < 0.05) increased at 20 min post treatment, peaked at 30 min, and gradually decreased to non-significant levels at 50 min post treatment when compared with the lidocaine and control groups. Additionally, xylazine produced a higher degree and longer duration of perineal analgesia than lidocaine. Systemically, epidural xylazine produced signs of sedation, salivation, vocalization and bradycardia. Ataxia was also observed in the xylazine-treated group which may have been induced through a local and/or systemic effect. The individual properties of xylazine and lidocaine should be taken into consideration when performing an obstetrical procedure requiring the use of an epidural analgesic agent, and they should be utilized to benefit the clinician in performing the procedure.     

肺癌根治术后不同镇痛方式的临床效果比较

目的：观察和比较硬膜外自控镇痛（PCEA）和静脉自控镇痛（PCIA）用于肺癌根治术患者围术期的镇痛效果及其不良反应的发生情况。方法：选择择期全麻下行肺癌根治性切除术的患者1214例,ASAI～II级,依镇痛方式不同分为硬膜外自控镇痛组（PCEA组,n=1023）和静脉自控镇痛组（PCtA组,n=191）。观察围术期两组患者镇痛效果、不良反应及术后康复情况。结果：PCEA组术后2h静止状态下和术后6h、24h活动状态下VAS评分均明显低于PCIA组（P〈O．05）;术后48h的Ramsay评分明显低于PCIA组（P〈0．05）;术后住院时间明显短于PCIA组（P〈0．05）;肺部并发症的发生率、切口感染和术后谵妄、恶心呕吐的发生率均明显低于PCIA组（P〈0．01）。结论：PCEA和PCIA两种镇痛方式用于肺癌根治术患者围术期均可达到满意的临床镇痛效果,但PCEA的用药量更少,镇静作用轻,副反应少,并可以降低肺感染和切口感染的几率,缩短住院时间,更有利于肺癌根治术患者的镇痛和康复。     

Continuous Epidural Analgesia for Labour and Delivery: Review of 1000 Cases

In six years in London, Ontario, the use of continuous lumbar epidural analgesia in deliveries increased from 5% to over 50%. Its effect was assessed in 1000 consecutive cases, all vertex presentations. In established labour, epidural analgesia was started for pain relief and was maintained with intermittent injections until delivery; in 34% the duration exceeded four hours. Labour was not retarded, but there was an inadvertent selection of patients with slow and painful progress. Forceps delivery was used in 89%, mid-forceps in 11.8% and forceps rotation in 17.7%; 2.4% required Cesarean section. Fetal condition was excellent (Apgar rating of 7 or greater in 96.7%). Postpartum complications could not be directly related to the technique. Continuous epidural analgesia gives superior relief of pain but calls for experienced anesthetists and adjustments in obstetrical management and nursing care.     

Fluid loading to reduce abnormalities of fetal heart rate and maternal hypotension during epidural analgesia in labour.

Fetal heart rate (FHR) was recorded and maternal blood pressure measured in 104 patients in whom lumbar epidural analgesia was induced in labour. Fifty-one patients received an intravenous load of 11 of Hartmann''s solution immediately before the epidural injection. This infusion significantly reduced the incidence of abnormalities of FHR from 34% to 12% and of maternal hypotension from 28% to 2%. We did not study mothers with pre-eclampsia and hypertension, but we conclude that there is a strong case for preloading all other mothers in whom lumbar epidural analgesia is induced in labour.     

Nicotene-induced analgesia in rats: The role of calcium and the diversity of responders and nonresponders

Following a single dose of nicotine, (NIC, 1 mg/kg s.c.), 60% of tested rats revealed significant anticociception as measured by the tail-flick (TF) test, and were classified as responders, with those in which TF latencies did not change, nonresponders. The following experiments were carried out one week later. In nonresponders, pretreatment with ethylenediaminetetraacetic acid (EDTA, 250 μM/kg s.c. four times every 15 min) followed by 1 mg NIC, produced significant analgesia in 50% of rats, to the same magnitude as did nicotene alone (1 mg) in responders. The other 50% of rats which failed to respond to EDTA pretreatment, all revealed similar analgesia following the higher dose of NIC (1.5 mg/kg s.c.), with similar side effects, as generally observed in responders. In responders, pretreatment with CaCl₂ (1.5 mM/kg s.c.) completely abolished NIC (1 mg/kg s.c.) - induced analgesia in all rats. Our data provide stronger evidence and a further verification that EDTA potentiates, whereas CaCl₂ completely abolishes, nicotene-induced analgesia in rats; supporting our hypothesis of the involvement of calcium ions in this effect.     

Oxytocin infusion during second stage of labour in primiparous women using epidural analgesia: a randomised double blind placebo controlled trial.

OBJECTIVE--To determine whether the high rate of forceps delivery associated with the use of epidural analgesia could be reduced through giving an intravenous infusion of oxytocin during the second stage of labour. DESIGN--A randomised, double blind, placebo controlled trial. SETTING--Delivery suites in three hospitals. SUBJECTS--226 Primiparous women with adequate epidural analgesia in whom full dilatation of the cervix had been achieved without prior stimulation with oxytocin. INTERVENTION--An infusion of oxytocin or placebo starting at the diagnosis of full cervical dilatation at an initial dose rate of 2 mU/min increasing to a maximum of 16 mU/min. MAIN OUTCOME MEASURES--The outcome of labour was assessed in terms of the duration of the second stage, mode of delivery, fetal condition at birth, postpartum blood loss, and the incidence of perineal trauma. RESULTS--Treatment with oxytocin was associated with a shorter second stage (p = 0.01), a reduction in the number of non-rotational forceps deliveries (p = 0.03), and less perineal trauma (p = 0.03) but was not associated with any reduction in the number of rotational forceps deliveries performed for malposition of the occiput. No adverse effects on fetal condition at birth or in the early puerperium were seen in association with the use of oxytocin. CONCLUSIONS--The use of an oxytocin infusion may reduce the high rate of operative delivery associated with epidural analgesia provided that the fetal occiput is in an anterior position at the onset of the second stage of labour but within the dose range studied does not seem to correct malposition of the fetal occiput.     

An evaluation of three anaesthetic regimes in the gray short-tailed opossum (Monodelphis domestica)

The effect of several anaesthetic agents on the gray short-tailed opossum (Monodelphis domestica) was investigated. Pentobarbitone sodium at a dose of 50 mg/kg sedated the animals but did not produce analgesia or anaesthesia. A combination of ketamine hydrochloride and xylazine at 40 mg/kg and 5 mg/kg, respectively, sedated the animals, but anaesthetic levels were not attained. Halothane was most effective in producing anaesthesia in Monodelphis domestica. Hypothermia was a major side effect with all three anaesthetic regimes.     

Evaluation of a combination of tiletamine and zolazepam as an anesthetic for laboratory rodents

A combination of equal parts of tiletamine hydrochloride and zolazepam hydrochloride was evaluated as an injectable anesthetic for rats, mice, and hamsters. The drug produced satisfactory anesthesia and analgesia in rats when given either intraperitoneally or intramuscularly at concentrations of 20 or 40 mg/kg body weight. The length of anesthesia was dose dependent and was somewhat longer in females as compared to males, and inbreds compared to outbreds. Incisions through the peritoneum of anesthetized rats evoked little or no response, whereas cervical skin incisions evoked a slight response in many rats. Anesthesia without analgesia occurred in mice at dosages of 80 mg/kg body weight and higher, however, many animals developed respiratory distress and died at dosages of 100 to 160 mg/kg body weight. In hamsters, anesthesia but not analgesia occurred at drug concentrations of 50 to 80 mg/kg body weight. It was concluded that a tiletamine and zolazepam combination was an effective anesthetic for rats, but not for mice or hamsters.     

In vivo covalent binding of [14C]trinitrotoluene to proteins in the rat.

When a single dose of [14C]trinitrotoluene was administered intraperitoneally (i.p.) to rats at 1, 10 or 50 mg/kg of body weight, covalently bound radioactivity was detected in globin, plasma proteins and proteins in the liver and kidney. The extent of covalent binding was dose dependent and was highest in plasma and renal proteins at all times up to 4 h after dosing. Covalent adduct levels in globin, however, decline slower than others. At a dose of 50 mg/kg of body weight, globin covalent adduct levels peaked at 1 h after dosing at 182 pmol/mg protein and subsequently decreased to approximately 50 pmol/mg protein between days 1 and 8. Of the covalent adduct levels in liver and kidney, those in the 10,000 x g and microsomal fractions were found to be higher than that in the cytosolic fraction. Radioactivity covalently bound to globin and the hepatic proteins was susceptible to dilute acid hydrolysis from which 2-amino-4,6-dinitrotoluene (2A) and 4-amino 2,6-dinitrotoluene (4A) were the major products recovered by solvent extraction. Upon acetylation, the hydrolysate gave rise to derivatives identified as the acetates of 2A and 4A on the basis of mass spectrometry and HPLC cochromatography with authentic samples. Four hours after an i.p. dose of [14C]TNT at 50 mg/kg of body weight about 0.4% of the dose was found as bound adducts to hemoglobin, of which approximately 48% was recovered as solvent extractable radioactivity after acid hydrolysis. About 2% of the radioactive dose was in the liver, of which approximately 30% was covalently bound to hepatic proteins, and approximately 49% of that was convertible to solvent extractable radioactivity upon acid hydrolysis. In vitro incubation of [14C]TNT with blood showed that there was a linear increase of covalent adducts in globin during the first 2 h of incubation; the concentration of covalent adducts was slightly higher than that with plasma proteins. The major compounds recovered from the hydrolysate of the globin adducts were also 2A and 4A as obtained from globin in the in vivo studies. On the basis of the in vitro and in vivo study results, we have confirmed the formation of protein adducts following a single i.p. administration of [14C]TNT at 1, 10 or 50 mg/kg of body weight to the rat or by in vitro incubation with blood.(ABSTRACT TRUNCATED AT 400 WORDS)     

家兔中脑导水管周围灰质中注射八肽胆囊收缩素（CCK—8）拮抗吗啡镇痛和...

We have reported that intracerebroventricular (i. c. v.) injection of 1-4 ng of CCK-8 to the rat produced a remarkable antagonistic effect on morphine analgesia. In order to study the species specificity and the site of action, CCK-8 was microinjected into the PAG of the rabbit, and its influence on morphine analgesia and electroacupuncture analgesia was observed. The latency of the escape response (ERL) to radiant heat focused on the snout was measured as an index of the pain threshold. Microinjections were made via cannulae chronically implanted into the PAG. The drug solutions were delivered in a volume of 1 microliter, at a speed of 0.125 microliter/min. The ERL was measured for a period of 60 or 70 minutes at 10 min intervals. 1. CCK-8 administered unilaterally to the PAG of the rabbit at a dose of 3 ng antagonized the analgesia induced by morphine (4 mg/kg, i. v.) by 73% (P less than 0.001), and reduced the analgesic effect of electroacupuncture by 67% (P less than 0.001). These effects were dose-dependent within the range from 1.5 ng to 6.0 ng. The effect of CCK-8 was reversed by CCK receptor blocker proglumide (4 microliters, intra-PAG injection). Unsulfated CCK-8 (CCK-us) had no effect in this regard. These results indicate that in the PAG of the rabbit, exogenously administered CCK-8 was capable of antagonizing opioid analgesia by the activation of CCK receptors. 2. Two groups of rabbits were given with morphine (2 mg/kg, i. v.) and simultaneous injection of CCK-8 antiserum (CCK-AS, 1 microliter) or normal rabbit serum (NRS) into the PAG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Novel drug designing approach for dual inhibitors as anti-inflammatory agents: implication of pyridine template

Compounds incorporating thiophene moiety, a pi excess five membered heterocycle, have attracted a great deal of research interest, owing to the therapeutic utility of the template as useful drug molecular scaffolding. We report the synthesis and pharmacological evaluation of thiophenes substituted with 4-methanesulfonyl benzoyl moiety at the fifth position of the ring, as possible anti-inflammatory lead candidates. The aryl sulfonyl methyl thiophene analogs AP29, AP82, and AP37, when screened for anti-inflammatory activity in carrageenin induced rat paw edema, an acute in vivo model, exhibited moderate to good activity at a dose level of 100 mg/kg body weight P.o compared to Ibuprofen. In a five day formalin induced rat paw edema, a chronic in vivo anti-inflammatory model, candidates AP29, AP82, and AP37 inhibited the disease progression by 53%, 34%, and 65%, respectively on the fifth day, at a dose level of 100 mg/kg body weight P.o compared to Rofecoxib, Ibuprofen, and Dexamethasone at therapeutic doses which gave a protection of 53.8%, 81.5%, and 81.5%, respectively. The replacement of the 4-methanesulfonyl benzoyl moiety in AP82 with the pyridine template, 3,5-dimethyl-4-methoxy-2-pyridyl function, gave rise to AP84, which was less active in the acute model, but gave 54% and 75% protection both during the first day and fifth day, respectively, in the chronic model. A dual mechanism of action is proposed for AP84, a non-steroidal drug which has exhibited remarkable activity when compared to the steroid dexamethasone. These results open up new avenues in designing novel anti-inflammatory drugs as dual inhibitors with the incorporation of a pyridine template as part of the pharmacophore.     

The influence of vasovasostomy on antisperm antibodies in rats

Serum antisperm antibodies were studied in Sprague-Dawley rats after vasectomy and vasovasostomy. Animals received a bilateral vasectomy, a vasectomy followed 3 mo later by vasovasostomy, or sham operations. Blood samples were obtained at 1, 3, 4, and 7 mo, and antisperm antibodies were assayed by an enzyme-linked immunosorbent assay. After vasectomy reversal was performed at 3 mo, antisperm antibodies were significantly higher in rats in the vasovasostomy group at 4 mo than in animals that had a persisting vasectomy or sham operations. At 7 mo, the antisperm antibody level for the vasovasostomy group was approximately double that for the vasectomized rats. Spermatic granulomas occurred in 76% of rats after vasovasostomy. Antisperm antibody levels were higher in vasovasostomized animals with granulomas than in those lacking granulomas. The results suggest that vasovasostomy may stimulate an antibody response to sperm rather than lead to a reduced response, as was anticipated upon removal of the obstruction. Spermatic granulomas may serve as sires for continued antigenic challenge. The observed increase in antisperm antibodies after vasovasostomy in Sprague-Dawley rats may be related to their relatively low immunologic responsiveness to vasectomy, with vasovasostomy serving as a second major immunologic challenge, aided by the formation of an additional granuloma. In the more responsive Lewis strain, we previously observed a rise in antisperm antibodies after the initial vasectomy, with no further increase after vasovasostomy.     

The interaction of protectants with EPTC on field bean, and tri-allate on wheat

Protectants (antidotes) were tested for their potential to protect field beans (Vicia faba L.) from EPTC damage, or wheat (Triticum aestivum L.) from triallate damage. For both crops there was considerable variation in the degree of protection shown from similar treatments in different experiments. For field bean, a seed treatment of 1,8-naphthalic anhydride (NA) at 5 mg/g seed gave some protection from EPTC applied pre-planting at 4–8 kg a.i./ha but not in all experiments. NA also caused marked chlorosis of the foliage. N, N-diallyl-2, 2-dichloroacetamide (R25788) at 20 mg/g seed severely damaged field bean in the absence of herbicide but 5 mg/g gave comparable protection from EPTC to that given by NA and did not cause chlorosis. Mixing R25788 with EPTC in the spray tank gave reduced protection. In a single experiment R4115 (chemistry undisclosed) gave some protection against EPTC damage. For wheat, a seed treatment of 5–20 mg/g NA sometimes countered damage from tri-allate applied pre-planting at 1 kg a.i./ha but not generally from higher doses. R25788 sometimes protected from weight loss due to tri-allate at 1 kg a.i./ha but not from damage symptoms, whereas R4115 at 20 mg/g seed alleviated these symptoms but did not prevent weight loss. R25788 at 4 kg a.i./ha mixed in the spray tank with the herbicide partially reduced weight loss and damage symptoms from a dose of 2 kg a.i./ha. Some treatments of R29148 gave complete protection from tri-allate at 1 kg a.i./ha. The results are discussed in the context of the full data from the two series of experiments.     

Antinociceptive, prolactin releasing and intestinal motility inhibiting activities of dermorphin and analogues after subcutaneous administration in the rat

A series of analogues and shorter homologues of dermorphin (DM), a frog skin heptapeptide with potent morphine-like activity, have been assayed in the rat after subcutaneous (SC) administration at the screening dose of 4 mg/kg. The effects taken into account are: analgesia (tail-pinch test), stimulation of prolactin (PRL) secretion, and inhibition of gastro-intestinal (GI) motility (charcoal meal transit). Effective doses were calculated for the most active compounds. The potency of DM (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) in the different tests was: tail-pinch: ED50 = 0.83 mg/kg; PRL release: ED100 = 0.3 mg/kg; inhibition of GI motility: ED30 = 1.8 mg/kg.     

Enterostatin (VPDPR) has anti-analgesic and anti-amnesic activities

Enterostatin (VPDPR), an anorexigenic peptide derived from the amino terminus of procolipase, significantly inhibited analgesia induced by the mu-opioid agonist morphine (5 mg/kg, s.c.) after i.c.v. administration to mice at a dose of 100 nmol. On the other hand, VPDPR (approximately 200 nmol, i.c.v.) did not attenuate analgesia induced by the kappa-opioid agonist D-Phe-D-Phe-D-Nle-D-Arg-NH2 (100 microg/mouse, i.c.v.) or delta-opioid agonist DTLET (4 nmol/mouse, i.c.v.). VPDPR (100 nmol, i.c.v.) significantly improved amnesia induced by scopolamine (0.2 mg/kg, i.p.) in mice. However, VPDPR did not enhance memory in normal mice at the same dose.