Diethylstilboestrol—historical background and current regulatory status

Diethylstilboestrol is a non-steroidal orally active oestrogen that in the past has been widely used in a variety of conditions in both medical and veterinary fields. In recognition of potential systemic availability to man of DES in the tissues of treated food-producing animals, together with an understanding of the potential teratogenic and carcinogenic toxicity of DES in man, the veterinary use of DES has been restricted to oral use in small animals only. Use of DES is prohibited in all food-producing animals.     

己烯雌酚免疫分析技术研究进展

己烯雌酚为人工合成的二苯乙烯类雌激素药物,曾经作为促生长剂广泛应用于畜牧业。但国内研究表明,己烯雌酚存在着潜在的致癌性。因此,近年来,其在饲料及动物性食品中的残留检测倍受关注,但己烯雌酚属于小分子化合物,不具备免疫原性。己烯雌激酚人工抗原主要采用混合酸酐反应(氯甲酸异丁酯法)将半抗原己烯雌酚与载体蛋白牛血清蛋白连接制备人工免疫原,并采用碳二亚胺法将半抗原己烯雌酚与载体蛋白卵清蛋白连接制备人工包被原。文章对己烯雌酚的免疫分析技术进行了综述。     

Anesthetic Potency of Desflurane in the Horse: Determination of the Minimum Alveolar Concentration

Objective — To determine the minimum alveolar concentration (MAC) of desflurane (DES) in the horse.
Study Design — Prospective study.
Animals — Six healthy adult horses (three males and three females) weighing 370 ±16 kg and aged 9 ±2 years old.
Methods — Anesthesia was induced with DES vaporized in oxygen via a face mask connected to a large-animal, semiclosed anesthetic circle system. The horses were endotracheally intubated and positioned in right lateral recumbency. Inspired and end-tidal DES were monitored using a calibrated Ohmeda RGM 5250 multigas analyzer (Ohmeda-BOC, Spain). The MAC of desflurane that prevented gross purposeful movement in response to 60 seconds of noxious electrical stimulation of oral mucous membranes was determined.
Results — The time from the start of DES administration to lateral recumbency was 6.1 ±0.9 min. The MAC of DES in these horses was 7.6 ±0.4%. Time required for the animal to regain sternal recumbency after 98 ±4 minutes of anesthesia was 6.6 ±0.5 minutes and the time to standing was 14.3 ±2.7 minutes.
Conclusions — The MAC of desflurane in these horses was 7.6 ±0.4%. DES provided a rapid induction to, and recovery from, anesthesia.
Clinical Relevance — Desflurane offers the potential for more precise control during anesthesia, and may allow a faster and uneventful recovery. It is important to know the MAC of an inhalant to use it clinically.     

Single-dose intravenous and oral pharmacokinetics of enrofloxacin in goral (Nemorrhaedus goral arnouxianus).

This study describes the pharmacokinetics of enrofloxacin following oral and i.v. administration to goral (Nemorrhaedus goral arnouxianus). The objective of this study was to expand upon current antimicrobial treatment options available for use in goral by measuring plasma concentrations and examining the pharmacokinetics of enrofloxacin in these animals. Two single-dose treatments of enrofloxacin were administered to four goral in a crossover design. Single-dose treatments consisted of administration of injectable enrofloxacin i.v. (5 mg/kg) and enrofloxacin tablets (136 mg chewable tablets) dissolved in a grain slurry and administered p.o. (10 mg/kg). Plasma levels of enrofloxacin and its metabolite ciprofloxacin were measured with the use of high-performance liquid chromatography with UV detection. Plasma volume of distribution for i.v. enrofloxacin was 2.15 - 1.01 L/kg, with a mean elimination half-life of 13.3 hr and total body clearance of 0.19+/-0.14 L/kg/hr. The maximum plasma concentration measured for oral enrofloxacin was 2.77 microg/ml, with a mean half-life of 5.2 hr and systemic availability of 14.6%. The area under the plasma concentration over time curve (AUC) for oral enrofloxacin was 21.06 microg/hr/ml. The area under the plasma concentration over time curve generated for oral enrofloxacin in goral yields an area under the plasma concentration over time curve to minimum inhibitory concentration ratio > 100 for many gram-positive and gram-negative bacterial pathogens common to small ruminants. Based on these results, oral enrofloxacin may be considered for further study as a treatment option for susceptible infections in goral.     

Cardiopulmonary effects of desflurane in horses

OBJECTIVE: To determine the cardiopulmonary effects of desflurane (DES) in horses. ANIMALS: Six healthy adult horses, three males and three females, aged 9 +/- 4 (mean +/- SD) years and weighing 370 +/- 36 kg. MATERIALS AND METHODS: Anaesthesia was induced with an O2 (10 L minute(-1)) and DES mixture (vaporizer setting 18%). After oro-tracheal intubation, horses were positioned in right lateral recumbency. Anaesthesia was maintained with DES in O2 (20 mL kg(-1) minute(-1)) delivered through a large animal circle breathing system. The minimum alveolar concentration of DES (MAC(DES)) that prevented purposeful movement in response to 60 seconds of electrical stimulation of the oral mucous membranes was determined for each horse. The delivered concentration of DES was then increased to achieve end-tidal concentrations corresponding to 1.5 x MAC(DES), 1.75 x MAC(DES), and 2.0 x MAC(DES). Heart rate (HR), mean arterial blood pressure (MAP), respiratory rate (fr), tidal volume (VT), minute volume (VM) and core temperature were determined, and blood samples for arterial blood gas analysis taken at each DES concentration. All data were analysed by two-way anova for repeated measures and Fisher's test for multiple comparisons. A probability level of p < 0.05 was applied. RESULTS: Desflurane concentrations of 2.0 x MAC(DES) increased HR whereas lower concentrations did not. Mean arterial pressure was not affected by 1.0 x MAC(DES) 1.5 x MAC(DES) or 1.75 x MAC(DES), whereas it decreased at 2.0 x MAC(DES). All concentrations of DES examined significantly depressed fr, VT and VM. CONCLUSIONS AND CLINICAL RELEVANCE: Desflurane concentrations between 1.0 and 1.75 x MAC(DES) reduces fr and VM but does not affect HR or MAP in horses.     

Instrumentation for external fixation.

External skeletal fixation is a very useful technique for managing many orthopedic problems in veterinary practice. The Kirschner apparatus has been the most widely used fixator for many years in veterinary orthopedics because of its versatility, simplicity, and economy in use. The medium-sized device has the widest indications and is easiest to begin with. The small size can be acquired later for use on cats and small dogs. The new "raised thread" fixation pin designs improve bone-pin integrity and can be used in combination with nonthreaded pins to decrease the incidence of postoperative complications and for economy. Acrylic-pin external fixators are particularly useful for treatment of mandibular fractures and transarticular application since they allow nonlinear placement of fixation pins in highly contoured bones. A commercial system, currently being developed, will have all the equipment and materials necessary for their application in a convenient kit. Circular fixators (Ilizarov design) use thin K wires placed under tension to replace rigid fixation pins. Their unique adjustability characteristics make them useful in the treatment of limb deformity and shortening. Many other human fixators can be used for veterinary application if the basic principles of fixators are followed. Instrumentation required for external fixator application include a pin driver, pin cutter, and wrenches. Although surgical versions of these materials are available, less expensive alternatives are available using gas sterilization instead of autoclaving. The use of selected orthopedic instrumentation such as a periosteal elevator, bone clamps, and curets will facilitate fracture management.     

Oral Cyclosporine Treatment in Dogs: A Review of the Literature

Cyclosporine is an immunomodulatory drug used to treat an increasing spectrum of diseases in dogs. Cyclosporine is a calcineurin inhibitor, ultimately exerting its inhibitory effects on T‐lymphocytes by decreasing production of cytokines, such as interleukin‐2. Although, in the United States, oral cyclosporine is approved in dogs only for treatment of atopic dermatitis, there are many other indications for its use. Cyclosporine is available in 2 oral formulations: the original oil‐based formulation and the more commonly used ultramicronized emulsion that facilitates oral absorption. Ultramicronized cyclosporine is available as an approved animal product, and human proprietary and generic preparations are also available. Bioavailability of the different formulations in dogs is likely to vary among the preparations. Cyclosporine is associated with a large number of drug interactions that can also influence blood cyclosporine concentrations. Therapeutic drug monitoring (TDM) can be used to assist in attaining consistent plasma cyclosporine concentrations despite the effects of varying bioavailability and drug interactions. TDM can facilitate therapeutic success by guiding dose adjustments on an individualized basis, and is recommended in cases that do not respond to initial oral dosing, or during treatment of severe, life‐threatening diseases for which a trial‐and‐error approach to dose adjustment is too risky. Pharmacodynamic assays that evaluate individual patient immune responses to cyclosporine can be used to augment information provided by TDM.     

己烯雌酚的研究进展

己烯雌酚（diethylstilbestrol，DES），是一种非甾体类雌激素。曾主要用于妇科疾病的治疗和促进动物生长。20世纪70年代中期发现孕期服用DES的女性其后代患生殖道癌症的风险明显增加而引起人们的广泛关注。经过30多年的大量研究结果表明DES残留对人体和环境都有明显的危害。但是目前关于是否该全面禁止DES的运用仍存在很大的争议。作者主要对DES的应用、毒副作用以及存在的争议作一综述。     

Lectin binding patterns in hyperplastic and metaplastic bullock prostate tissues after diethylstilbestrol administration

Hyperplasia and squamous metaplasia of the prostatic epithelium are conditions induced by oestrogens. Diethylstilbestrol (DES) has been banned from cattle used for beef production because of the health risks. The potential use of molecular markers for the detection of illegal oestrogen administration was evaluated by taking samples of prostatic tissue from control bullocks, bullocks which had been treated with oestrogens, and bullocks sacrificed 21 and 90 days after a single dose of DES. The expression of the glycoconjugates was examined by lectinhistochemistry and the lectin binding pattern was characterised in epithelium and connective tissue. In the animals sacrificed after 21 days there was an increase in the binding of one lectin (JAC) and there was an increase in the binding of one of the other lectins (DBA) in the animals sacrificed after 90 days. An increase in SWGA lectin staining was observed in the bullocks that had probably been treated with oestrogen and in the animals sacrificed 90 days after the inoculation with DES. There were also differences between the binding of SWGA in the control bullocks and the other groups.     

Chloramphenicol 3. Clinical pharmacology of systemic use in the horse

The use of chloramphenicol in the horse is now prohibited as horses are classified as food-producing animals. However, chloramphenicol has until recently been widely available for oral, intramuscular or intravenous administration. A critical appraisal of the published literature on the use of chloramphenicol in the horse clearly demonstrates that there are sound pharmacokinetic and microbiological reasons for concluding that chloramphenicol is not an appropriate antibiotic for systemic use. The short half-life of chloramphenicol in the horse, together with the broad range of minimum inhibitory concentrations of target pathogens, preclude the use of practical dosage regimens. It can be concluded that the withdrawal of chloramphenicol will have no adverse effects on chemotherapy in the horse.     

Recovery of fertility in quinestrol‐treated or diethylstilbestrol‐treated mice: Implications for rodent management

Fertility control is an alternative strategy to traditional culling for the management of rodent pests. Previous studies have demonstrated that quinestrol is a potential contraceptive for male rodents, but the recovery of fertility in quinestrol‐treated rodents has not been evaluated. This study used C57BL/6J mice to evaluate the recovery rate of male fertility after the administration of quinestrol. Diethylstilbestrol (DES), a non‐steroid estrogenic compound, was used for comparison. Different groups of mice were treated with 1 mg/kg quinestrol, 1 mg/kg DES, or castor oil separately for 7 days. These mice were then killed on days 8, 22 and 50 respectively. Our results indicated that the weight of epididymides and seminal vesicles decreased significantly on days 8 and 22 in quinestrol/DES‐treated mice, with extensive histological changes in the seminiferous tubules. Sperm concentrations in the cauda epididymal fluid were significantly reduced on days 8 and 22 in both quinestrol and DES treatment groups and on day 50 for the DES, but not the quinestrol group. Further analysis revealed that DES‐treated mice exhibited a higher proportion of abnormal sperm accumulation in the epididymis, indicating that the normal sperm transportation to the cauda epididymis was blocked. Our results indicate that the anti‐fertility effects on male mice given quinestrol were of shorter duration than for those receiving DES at the dose of 1 mg/kg body weight.     

Excretion pattern of enrofloxacin after oral treatment of chicken broilers

The metabolism and excretion of enrofloxacin were studied when applied as oral solution to chicken broilers for five consecutive days. Sixty 9‐day‐old broilers were isolated within an intensively rearing poultry farm during enrofloxacin therapy (15.5 mg/kg per day). The excreta of the isolated broilers were collected daily, 9 days after therapy termination, for 13 consecutive days, and analyzed for the presence of enrofloxacin and its metabolites [ciprofloxacin, desethylene‐enrofloxacin (DES‐EF) and desethylene‐ciprofloxacin (DES‐CF)]. Enrofloxacin was excreted predominantly in the form of the parent compound between days 1 and 13. Ciprofloxacin was detected in the excreta between days 1 and 6, whereas minor amounts of DES‐EF and DES‐CF were excreted only between days 1–7 and 1–6, respectively. In conclusion, the analysis of the excreta showed that approximately 74% of orally applied enrofloxacin was excreted as the parent compound, approximately 25% as the main metabolite ciprofloxacin, and approximately 1% as the minor metabolites desethylene‐enrofloxacin and desethylene‐ciprofloxacin.     

Antithrombotic Therapy

Thrombosis or thromboembolism are significant concerns in companion animals and can be associated with cardiac, metabolic, neoplastic disease processes or can be one manifestation of inflammatory, infectious, and neoplastic disease conditions. Options for thromboprophylaxis available for clinical use in small animal patients are very limited, with heparin (primarily unfractionated, but more recently low-molecular-weight forms) and aspirin predominating. Controlled studies evaluating the use of these drugs are few, but there is some limited evidence for efficacy in prevention of formation of thrombi. Use of the vitamin K antagonist warfarin has been described, but the narrow therapeutic window has resulted in a high rate of serious adverse events. In human patients, the efficacy of aspirin, heparins, and vitamin K antagonists is well documented in a variety of thrombotic conditions, but there are significant limitations to each of these options. These limitations have prompted the search for new alternatives, some of which are now in wide clinical use in humans. Although the use of some of the drugs discussed here has not yet been described in veterinary patients at risk for thrombosis, many of these agents have been evaluated experimentally in dogs, cats, or both. These new thromboprophylactic agents may soon be beneficial in management of small animal patients at risk for thrombosis.     

Effective control for diethylstilbestrol in cattle in the Netherlands

In the period from August 1981 to April 1983, 10243 random samples of urine from slaughtered cattle were inspected for the presence of the stilbene derivatives diethylstilbestrol (DES), dienestrol (DE), and hexestrol (HEX). Fast screening of all samples was performed by radioimmunoassay (RIA) with prior clean-up column chromatography. In this screening, 216 samples were indicated for confirmatory analyses by combined high performance liquid chromatography-gas chromatography-mass spectrometry (HPLC-GCMS) on account of an immunochemical response equivalent to 1 microgram/1 DES or more. The presence of DES was confirmed in 184 samples, DE in 5 samples and HEX in 14 samples. In the remaining 13 samples no stilbene derivative could be confirmed. From the results in 1984, after the introduction of the Meat Inspection Act, it is concluded that the use of stilbene derivatives in cattle in the Netherlands has dropped almost to zero. Of 4558 samples investigated, only 6 (0.13%) were indicated as 'stilbene' positive. The presence of DES was confirmed in 2 samples and DE in 4 samples.     

Malabsorption due to selected oral antibiotics

This article represents an overview of recent research conducted on antibiotic-induced malabsorption in calves. The authors feel strongly that this work identifies a serious and ill-defined problem in the management of neonatal calves. Too often the solution utilized by veterinarian and stockmen for controlling neonatal diarrhea has been to administer oral antibiotics. In many cases, this has been done on the basis of antibiotic sensitivity testing, an approach that seems appropriate. Unfortunately, little consideration has been given to the relative sensitivity of the neonatal intestinal mucosa, with its very rapid turnover, to the potentially detrimental effects of oral antimicrobial therapy. The data that we have collected over the past 3 years conclusively demonstrate that high levels of four commonly used oral antibiotics, especially neomycin and chloramphenicol but also tetracycline and ampicillin, can cause a malabsorption diarrhea in normal calves. This action is not due to viral agents or overgrowth of resistant microbes but is the result of direct modification of the intestinal mucosa. Extrapolation of these data to different dose levels may not be accurate. Oral antibiotics may be of value in treating neonatal enteritis. Conversely, there can be too much of a good thing, and many cases of chronic diarrhea following use of oral antibiotics may be the result of an overenthusiastic and prolonged dosage regimen. Be cautious!     

Reconstruction of oral defects using mucogingival pedicle flaps

There are many oral pathological conditions that greatly impact the health and the longevity of small animals and require surgical closure. Surgical treatment success is dependent on an accurate diagnosis of the problem. The pet's signalment, medical history, clinical signs, and adjunctive diagnostics (radiographs and histology) are all used concurrently to ascertain a working diagnosis. Once determined, the pathology's management and the subsequent reconstruction of normal anatomy become the surgeon's goals. The use of mucogingival flaps in this reconstruction process is integral to the therapy's success. The oral cavity's abundant blood supply and rapid healing allow these flaps to be well tolerated by the animal and quite resistant to breakdown. Flap designs and implementation are important to this healing process. This article discusses 4 diverse oral cases. Their presentations, diagnoses, and surgical corrections are discussed to show how mucogingival flaps may be used in closures of oral surgical defects.     

A review of pre-appointment medications to reduce fear and anxiety in dogs and cats at veterinary visits

This review focuses on pre-appointment medications used to decrease fear and anxiety in dogs and cats related to veterinary visits. A review of the literature revealed data on 4 medications from 4 medication classes that have been used to ameliorate acute situational fear and anxiety in dogs and cats: gabapentin, trazodone, oral transmucosal dexmedetomidine, and alprazolam. The available information on use, mechanism of action, and pharmacokinetics is reviewed.     

Effective control for diethylstilbestrol in cattle in the Netherlands

Summary

In the period from August 1981 to April 1983, 10243 random samples of urine from slaughtered cattle were inspected for the presence of the stilbene derivatives diethylstilbestrol (DES), dienestrol (DE), and hexestrol (HEX). Fast screening of all samples was performed by radioimmunoassay (RIA) with prior clean‐up column chromatography. In this screening, 216 samples were indicated for confirmatory analyses by combined high performance liquid chromatography‐gas chromatography‐mass spectrometry (HPLC‐GCMS) on account of an immunochemical response equivalent to 1 μg/ 1 DES or more. The presence of DES was confirmed in 184 samples, DE in 5 samples and HEX in 14 samples. In the remaining 13 samples no stilbene derivative could be confirmed.

From the results in 1984, after the introduction of the Meat Inspection Act, it is concluded that the use of stilbene derivatives in cattle in the Netherlands has dropped almost to zero. Of 4558 samples investigated, only 6 (0.13%) were indicated as ‘stilbene’ positive. The presence of DES was confirmed in 2 samples and DE in 4 samples.     

Mycotoxins.

The relevance of many mycotoxins to small animal health is difficult to assess, because available information has not been collated and reviewed. Only aflatoxins, penitrem A, and roquefortine have been confirmed in natural mycotoxicoses in pets. Effects of tricothecene mycotoxins, patulin, and penicillic acid on dogs and cats have only been studied experimentally and have not been confirmed in natural outbreaks. Although they make up only a small portion of the cases presented to veterinarians, mycotoxicoses often require special effort. Establishing an accurate diagnosis is crucial to minimize exposure and provide adequate treatment. In most cases, clinical examination, clinical pathologic testing, and analytical chemistry analysis of suspect feed are necessary to reach a diagnosis.     

Total serum bile acids and the bile acid profile as tests of liver function

Total serum bile acid assay for the evaluation of liver function has been available for many years but its application has been limited primarily by factors such as methodology, equipment and cost. New and improved methods for bile acid assay such as the radioimmunoassay or the hydroxysteroid dehydrogenase techniques have brought the assay for bile acids into the realm of the clinical laboratory. The efficacy of bile acids for clinical diagnostic use in the evaluation of liver function has not been firmly established. Newer methods using high pressure liquid chromatography to develop a profile of the different bile acids may clarify its usefulness and define its role among the many available tests of liver function in animals.