Parenteral use of medroxyprogesterone acetate as an antifertility agent in the bitch

10 kg unbred Beagle and mongrel bitches were used in each of 4 experiments (exp). 6 alpha-methyl-17 alpha-acetoxyprogesterone (MAP or medroxyprogesterone acetate) was prepared as a sterile aqueous suspension (50 mg/ml) and was used in exps 1, 2 and 3. Tritiated MAP was used in exp 4. In exp 1, 7 bitches were given 500 mg and 7 were given 50 mg subcutaneously (sc). 6 controls were used. In exp 2, 50, 100 or 250 mg were given sc, intramuscular (im) or intraperitoneal (ip) to 4 dogs at each dose level and route of administration. In exp 3, 12.5 or 25 mg was given either sc or im in 4 groups of 8 bitches each. In exp 4, a single 50 mg mixture of MAP and tritiated MAP was given to each of 3 dogs: 1 sc, 1 im, and 1 ip. Results of exp 1 showed those on 500 mg had first posttreatment estrus an average of 504 days (range of 247-730) after injection. Those on 50 mg averaged 329 days (range of 205-429). Breeding resulted in 6 live pups/litter for the controls 5.2 for those on 50 mg, and 4 for those on 500 mg. In exp 2, results showed prolonged cycling in those injected sc (295 days to estrus), while those injected im reached estrous in 225 days and those injected ip in 148 days. In exp 3, 3 on 25 mg sc had a 6 month estrous delay while 4 did when injected im. 3 of 16 given 12.5 mg sc and im had a 6 month delay in cycling. Exp 4 showed ip treated dogs had estrus 148 days after treatment, 225 days for im, and 295 days for sc. Ip treated dogs whelped 5 pups; im 7 pups; and sc, 5 pups. 7 months lapsed before nearly all of the 50 mg sc administered dose was excreted. An additional 2.5 months lapsed before estrus occurred in this dog.     

Use of fenbendazole suspension (10%) against experimental infections of Toxocara canis and Ancylostoma caninum in beagle pups

Eleven nematode-free Beagle pups were inoculated with Ancylostoma caninum and Toxocara canis; infection became patent 13 and 35 days later, respectively. Eight pups were treated with fenbendazole oral suspension (10%) at a dosage of 50 mg/kg of body weight/day for 3 days. The remaining three animals were unmedicated controls. The drug was effective in reducing both ascarid and hookworm burdens, and there was marked improvement in the clinical condition of treated pups as compared with unmedicated control pups. Natural expulsion of worms in control animals was 53% for ascarids and 2% for hookworms. Drug-related toxicosis was not observed in any of the medicated animals. It was concluded that fenbendazole oral suspension (10%) at the 50-mg/kg dosage is easily administered and is an effective drug for reducing nematode burdens in experimentally infected pups.     

Factors affecting the efficacy of ivermectin against Heligmosomoides polygyrus (Nematospiroides dubius) in mice

The efficacy of ivermectin against Heligmosomoides polygyrus was investigated in 5 mouse strains (CFLP, NIH, C57Bl10, BALB/c and CBA) using a variety of dose levels, and subcutaneous and oral administration. Heligmosomoides polygyrus were not completely eliminated when 5 mg kg-1 of ivermectin was given 6 days after infection, but 10 mg kg-1 was totally effective. Significant mouse-strain variation in drug efficacy was detected, NIH mice requiring treatment with higher doses than CFLP mice in order to bring about a comparable level of larvicidal activity. Ivermectin was more effective when given subcutaneously than when given orally, regardless of the dose administered or the strain of mouse tested. The anthelmintic effect of the treatment was more persistent in CFLP mice given 20 mg kg-1 subcutaneously than in NIH mice or in mice treated orally, and a 20-day interval between administration and infection was insufficient to prevent inhibition of parasite survival. Ivermectin was shown to be totally effective at 20 mg kg-1 given subcutaneously in killing immune arrested larvae of H. polygyrus.     

Neosporosis in dogs

A bitch was inoculated subcutaneously and intramuscularly with Neospora caninum tachyzoites on Day 35 of pregnancy. Eight pups were born 28 days later. Five pups became ill and necropsies were performed before 20 days of age. Three pups and the bitch remained clinically normal for 7 weeks after parturition when they were intramuscularly injected with 40 mg kg-1 methylprednisolone acetate weekly to activate chronic N. caninum infection. Necropsies were performed 48, 17, 18, and 18 days respectively after administration of corticosteroids. Hepatic necrosis, pneumonia, encephalomyelitis, and myonecrosis were the main changes seen in these dogs.     

Efficacy of selamectin administered topically to pregnant and lactating female dogs in the treatment and prevention of adult roundworm (Toxocara canis) infections and flea (Ctenocephalides felis felis) infestations in the dams and their pups

The efficacy of selamectin in the treatment and prevention of naturally acquired Toxocara canis infections and experimentally induced flea (Ctenocephalides felis felis) infestations in dams and their suckling pups was evaluated by administering selamectin to the adult females only, approximately 40 and 10 days before parturition and 10 and 40 days after parturition. Unit doses of the commercial formulation of selamectin were administered to the dams to provide at least the minimum recommended dosage of 6mgkg(-1) (range, 6-12mgkg(-1)). Dams and their pups were housed in carpeted environments able to support the flea life cycle. Flea infestations were established initially by experimental infestation before treatment administration and by repeated re-infestation of dams at approximately weekly intervals throughout the study, which was completed 45 days after parturition. There were no adverse drug experiences related to treatment with selamectin and no treatment-related mortalities. Percentage reductions in geometric mean T. canis faecal egg counts for the selamectin-treated dams, compared with those receiving the negative-control treatment (vehicle only) were 99.7% at the end of the study (P=0.0001). Geometric mean faecal egg counts in pups from selamectin-treated females were reduced by > or =96% on the 24th and 34th days after birth (P=0.0001), and the number of adult worms recovered from the gastrointestinal tract of pups from selamectin-treated dams was reduced by 98.2% (P=0.0001), compared with that for pups from dams treated with the vehicle only. Percentage reductions in geometric mean flea counts for selamectin-treated dams and their pups, compared with vehicle-treated dams and their pups, were > or =99.8% (P=0.0001) and 100% (P=0.0001), respectively, throughout the study. Thus, selamectin administered topically at a minimum unit dosage of 6mgkg(-1) to dams with naturally acquired T. canis infections and experimentally induced C. felis infestations was safe and highly effective in the treatment, control, and prevention of adult T. canis infection and C. felis infestation affecting both the dams and their pups.     

Penetration of ceftiofur into sterile vs. Mannheimia haemolytica-infected tissue chambers in beef calves after subcutaneous administration of ceftiofur crystalline free acid sterile suspension in the ear pinna

The effect of Mannheimia haemolytica infection on the penetration of ceftiofur and desfuroylceftiofur metabolites into tissue chambers was studied in cattle after subcutaneous administration of ceftiofur crystalline free acid sterile suspension (CCFA-SS). Four tissue chambers were implanted subcutaneously in each of 12 calves. Approximately 45 days after implantation, two chambers were inoculated with M. haemolytica (10(6) colony-forming units per chamber) while the remaining two chambers were inoculated with sterile phosphate-buffered saline. Twenty-four hours after inoculation, CCFA-SS was administered subcutaneously in the middle third of the caudal ear pinna of each calf. Chamber fluid and blood samples were collected at predetermined times for 10 days following dosing and analyzed for ceftiofur and desfuroylceftiofur metabolites by high-performance liquid chromatography. Concentrations of ceftiofur and desfuroylceftiofur metabolites in plasma and tissue chamber fluid remained above a threshold of 0.2 microg/mL for at least 8 days. Infected tissue chamber fluid concentrations of ceftiofur and desfuroylceftiofur metabolites were significantly higher than those in non-infected tissue chamber fluid, which correlated with significantly higher total protein concentration in infected tissue chambers. These results indicate that single subcutaneous administration of CCFA-SS at 6.6 mg/kg can be expected to provide effective therapy of susceptible bacterial infections for a period of at least 1 week.     

Safety study of a beef-based chewable tablet formulation of ivermectin and pyrantel pamoate in growing dogs, pups, and breeding adult dogs.

To determine the safety of a new combination of ivermectin and pyrantel (as pamoate salt) in a novel beef-based chewable tablet formulation, 3 tolerance trials were conducted and included growing dogs, pups, and breeding adult dogs. Growing dogs, given the combination orally for 5 consecutive days at recommended dosages (5 mg of pyrantel/kg of body weight, 6 micrograms of ivermectin/kg) or at twice the pyrantel dosage in combination with the recommended dosage of ivermectin, had no adverse effects. The combination also was administered to 6-week-old pups at 1, 3, and 5 times the recommended dose on 3 successive days for 3 times in 1 month. Compared with age-matched controls, treatment had no effect on clinical status, growth rate, or gross or histologic features. Breeding male and female dogs given the combination at 3 times the recommended dose for extended periods had no adverse effects, and prevalence of abnormalities in the offspring was not greater than that in nonmedicated controls.     

Recrudescence of infectious bovine rhinotracheitis virus and associated neural changes in calves treated with dexamethasone

Reactivation of infection bovine rhinotracheitis (IBR) virus in calves administered dexamethasone (DM) was studied in 2 experiments. At 2, 3, 5, 15, or 30 months after inoculation of the Los Angeles strain of IBR virus, IV injections of DM were given for 5 consecutive days to induce a recurrent infection (experiment 1). Three months after the 1st treatment, a 2nd recurrent infection was induced, using DM with the same doses as used in experiment 1. The virus was excreted from nasal secretions from the 4th to the 10th day after initial treatment with DM, and from the 6th to the 9th day after the 2nd treatment. On pathologic examination, trigeminal ganglionitis, consisting of many proliferated microglia and inflammatory cells, was observed in all DM-treated calves. Moreover, degeneration of the ganglion cells and neuronophagia were prominent features in the calves after the 2nd recurrent infection. These observations indicated that the trigeminal ganglion may be one of the latent sites of IBR virus in calves after intranasal infection and that calves can develop a recrudescent infection after DM treatment several times during their lifetime.     

Evaluation of bupivacaine liposome injectable suspension efficacy in single-use vials over five days of multiple use

ObjectiveTo test the anesthetic effect of a bupivacaine liposome injectable suspension (BLIS), used in a multiple-dose manner for up to 5 consecutive days.Study designProspective, randomized, experimental study.AnimalsA total of 30 male and female Sprague–Dawley rats (Rattus norvegicus), aged 97 (75–130) days and weighing 337.2 (219.6–465.9) g, mean (range).MethodsRats were assigned to one of five BLIS vial groups, in which drug was administered from a newly opened vial or 1, 2, 3 and 4 days after the vial was opened. The vials were refrigerated between uses. A 14 gauge needle attached to an injection plug was used to puncture each vial once and was not removed; BLIS was withdrawn from the injection plug in a multiple-dose fashion. A dose rate of 0.4 mL kg⁻¹ was administered subcutaneously into the left pelvic limb paw. Antinociception was evaluated using a paw pressure test on both injected and uninjected paws before (time 0, baseline) and 1, 24, 48 and 72 hours after injection.ResultsAge of BLIS vial had no significant effect on anesthetic efficacy (p = 0.97). Across all groups, paw withdrawal latency averaged 5.23 ± 0.24 seconds at baseline (before BLIS injection), increased to 16.45 ± 0.65 seconds at 1 hour after BLIS injection, declined to 7.50 ± 0.76 seconds at 24 hours after BLIS injection, and further declined thereafter (p < 0.001). There was no significant change in paw withdrawal latency in the uninjected paw over time.Conclusions and clinical relevanceBLIS single-use vials retained efficacy when used up to 5 days in a multiple-dose fashion. Because anesthetic effects declined substantially after 24 hours, multimodal pain management remains important for providing analgesia care.     

Efficacy of fenbendazole granules and pyrantel pamoate suspension against Toxocara canis in greyhounds housed in contaminated runs.

The efficacy of fenbendazole granules against Toxocara canis in naturally infected greyhounds housed in contaminated environments was evaluated. Eight pens, each containing three to seven greyhounds, 3-12 months of age, were randomly allotted into two treatment groups. Greyhounds in Group 1 were treated with fenbendazole granules mixed in their feed at 50 mg/kg/day for 3 consecutive days once a month for 4 months. Greyhounds in Group 2 were treated with pyrantel pamoate suspension at 5.0 mg/kg per os once a month for 4 months. Quantitative fecal examinations were performed on days 0, 10 and then on the first day of each monthly treatment. Greyhounds administered fenbendazole had fecal egg count reductions (FECRs) of 95.8 and 99.8% at 10 and 31 days following initial treatment, respectively. Greyhounds administered pyrantel pamoate had FECRs of 85.8 and 88.3% at 10 and 31 days after the first treatment, respectively. T. canis fecal egg counts conducted from Day 31 through Day 128 were significant lower in those greyhounds administered fenbendazole as compared to greyhounds administered pyrantel pamoate. Fenbendazole produced FECRs in greyhounds from Day 31 through Day 128 by 96.8-99.8%. Pyrantel pamoate reduced fecal egg counts during the same time period 71.4-98.3%.     

Preliminary investigation of a possible lung worm (Parafilaroides decorus), fish (Girella nigricans), and marine mammal (Callorhinus ursinus) cycle for San Miguel sea lion virus type 5

Colostrum-deprived neonatal Northern fur seal pups (Callorhinus ursinus) were exposed to San Miguel sea lion virus type 5 (SMSV-5) by feeding them fish (Girella nigricans) infected with virus or fish infected with both the sea lion lung worm larvae (Parafilaroides decorus) and virus. Virus infection was demonstrated in 8 of 9 pups, and 1 of these developed a vesicular lesion on the flipper. In this sequence, P decorus larvae exposed to SMSV-5 were fed to G nigricans held at 15 C in a salt water aquarium; 32 days later, these fish were killed, then fed to the fur seal pups. The vesicle developed 22 days subsequent to this and SMSV-5 was reisolated from the lesion. The SMSV-5 was shown to persist for at least 23 days in infected neonatal fur seals. Attempts to establish P decorus infection in Northern fur seal pups were apparently unsuccessful.     

Effects of administration of prostagrandin F(2)(alpha)-analogue fenprostalene on canine corpus luteum and subsequent recurrence of estrus and fecundity

The effects of the long-acting prostagrandin F(2)(alpha)-analogue fenprostalene were investigated. Twenty-three female beagles (24 cases) 1-6 years of age were divided into 6 groups, and a dose of 5-150 microg/head of fenprostalene was subcutaneously administered at 25 days after ovulation to investigate its effects based on peripheral blood progesterone (P(4)) levels. The dogs were also examined for shortening of their estrous cycle after administration and fecundity after the recurrence of estrus. The results showed that the administration of 50 microg/head of fenprostalene or more reduced the levels of peripheral blood P(4) to about 1 ng/ml 2 days after administration, indicating early regression of the corpus luteum, and that the administration of these doses shortened the time to the subsequent estrus by a mean of about 80 days, and that conception rates were normal if estrus recurred about 2 months after fenprostalene administration or later.     

Expression and purification of canine granulocyte colony-stimulating factor (cG-CSF)

Canine granulocyte colony-stimulating factor (cG-CSF) with modification of cysteine at position 17 to serine was expressed in Brevibacillus choshinensis HPD31. cG-CSF secreted into the culture medium was purified by ammonium sulfate precipitation and consecutive column chromatography, using butyl sepharose and DEAE sepharose. Biological activity of the recombinant cG-CSF was 8.0 × 10⁶ U/mg protein, as determined by its stimulatory effect on NFS-60 cell proliferation. Purified cG-CSF was subcutaneously administered once a day for two successive days to dogs (1, 5, 25, or 125 μg). Neutrophil count increased the following day in all dogs except those administered the lowest dose (1 μg). No severe side effects were observed in dogs after administration of cG-CSF.     

Chemoprophylactic effects of milbemycin oxime against larvae of Dirofilaria immitis during prepatent development.

Three studies were conducted to determine the efficacy of milbemycin oxime in the prevention of Dirofilaria immitis infection in dogs. Dogs were given single or multiple experimental inoculations with infective third-stage D immitis larvae and were treated with milbemycin oxime at a target dosage of 0.5 mg/kg of body weight either once or at monthly intervals at various times after inoculation. The compound was effective in preventing infection when 1 dose was administered 30 or 45 days after inoculation. Significant, but incomplete, protection was achieved when single treatments were administered 60 or 90 days after inoculation. Multiple monthly treatments beginning 60 days after inoculation appeared to provide additive effects that resulted in restoration of complete efficacy.     

Clinical Use of Deslorelin for the Control of Reproduction in the Bitch

This study was conducted to evaluate clinical efficacy of deslorelin for inhibiting reproduction in the bitch. Ten adult healthy bitches or bitches with mammary neoplasia for which owners were requesting suppression of cyclicity without performing gonadectomy were administered a 4.7- or a 9.4-mg deslorelin implant subcutaneously. The first implant of deslorelin was administered in anoestrus (n = 5) or in dioestrus (n = 5). Treatment was repeated every 5 months for as long as necessary based on the clinical situation of the dog and owner's desires. Some of the bitches implanted in anoestrus came in heat within 4–15 days after treatment, while none of the bitches implanted in dioestrus showed heat during treatment. Suppression of reproductive cyclicity was successfully achieved in 6/10 bitches for 1–4 years. No behavioural and local/general side-effects were observed in any of the treated bitches. The 4.7-mg deslorelin implant may work well for suppression of cyclicity provided that it is administered in dioestrus and at intervals of 4.5 months. A 9.4-mg implant may be more suitable for this use although its efficacy may also be shorter than 12 months. Owner compliance is an important limiting factor.     

Effects of experimentally induced Pasteurella haemolytica infection in dairy calves on the pharmacokinetics of flumequine

The effect of experimental Pasteurella haemolytica infection on the intravenous and intramuscular pharmacokinetics of flumequine was studied in dairy calves. The plasma concentration-time curve of flumequine after intravenous injection of 5 mg/kg bodyweight flumequine of a 10% solution before and after experimental infection, was best described by a three-compartment open model. After intramuscular injection of the same dosage rate of a 3% flumequine suspension is was best described by the one-compartment open model with first-order absorption. The experimental infection by intratracheal administration of infectious bovine rhinotracheitis (IBR)-virus and 5 days later intrapulmonary administration of Pasteurella haemolytica produced a clear temperature rise and signs of disease expressed as Average Health Status. Subsequently, plasma Fe and Zn concentration decreased after infection. The distribution volumes Vc, Vd(area) and Vd(ss) after infection (0.07 +/- 0.04, 1.38 +/- 0.36 and 0.50 +/- 0.11 l/kg, respectively) were smaller than those before infection, but the differences were not significant (P less than or equal to 0.1). The intravenous AUC infinity was significantly increased (21.86 +/- 3.51 to 33.85 +/- 2.97 mg.h/l, P less than or equal to 0.01) and the total body clearance (ClB) significantly decreased (0.24 +/- 0.02 to 0.15 +/- 0.01, P less than or equal to 0.01) after infection. After intramuscular injection of flumequine at 5 mg/kg as a 3% suspension, only the bioavailability, F, was significantly decreased after infection (78.5 +/- 14.3 to 59.7 +/- 21.2%, P less than or equal to 0.02). However, this had no consequences for the dosage regimen used. The urine concentration ratio flumequine:7-hydroxy-flumequine:conjugated flumequine changed from 2:1:10 before infection to 6:1:15 after infection, which indicates that hydroxylation and glucuronidation as metabolic pathways for flumequine were decreased after Pasteurella sp. infection.     

不同剂型氟苯尼考对实验性鸡大肠杆菌病的疗效

以人工诱发鸡大肠杆菌病为模型,研究了不同剂型氟苯尼考的疗效。15日龄AA鸡随机分组,除健康对照组外,各组动物均肌肉注射大肠杆菌(O78)肉汤培养物诱发大肠杆菌病。氟苯尼考预混剂(100 mg/kg拌料)、可溶性粉(100 mg/L饮水)和注射剂(20mg/kg肌注)分别于攻毒前24 h、攻毒同时及攻毒后4 h给药。主要以各组动物存活数为标准评价疗效。结果表明,氟苯尼考预混剂、可溶性粉和注射剂对鸡大肠杆菌病的有效率分别为70%、90%和93.3%,而感染对照组的死亡率为73.3%,试验各组之间鸡的增重差异不显著。试验结果提示氟苯尼考饮水剂和注射剂可有效控制重症大肠杆菌病,预混剂可作为预防用药或用于治疗早期轻度感染。     

Experimental infection of ponies with Borrelia burgdorferi by exposure to Ixodid ticks

Seven specific-pathogen-free (SPF) ponies, 1-5 years old, were exposed to Borrelia burgdorferi-infected adult ticks while being treated with dexamethasone over 5 consecutive days. One SPF pony (pony No. 178) was first exposed to laboratory-reared nymphs without B. burgdorferi infection and 3 weeks later was exposed to B. burgdorferi-infected adult ticks with concurrent dexamethasone treatment for 5 consecutive days. Four uninfected ponies treated with dexamethasone, exposed to laboratory-reared ticks without B. burgdorferi infection served as uninfected controls. Clinical signs, bacteriologic culture, polymerase chain reaction (PCR) for bacterial DNA, immunologic responses, and gross lesions and histopathologic changes were investigated during the experiment or at necropsy 9 months after tick exposure. In all of the seven challenged ponies, infection with B. burgdorferi was detected from monthly skin biopsies and various tissues at postmortem examination by culture and by PCR. However, pony No. 178 exposed to laboratory-reared nymphs (without B. burgdorferi infection) and challenged with B. burgdorferi-infected adult ticks 2 months later did not develop a B. burgdorferi infection. All of the infected ponies seroconverted. Control ponies and pony No. 178 were negative by culture, PCR, and serology. Except for skin lesions, we failed to induce any significant histopathologic changes in this study. This is the first report of successful tick-induced experimental infection in ponies by exposure to B. burgdorferi-infected ticks. This Lyme disease model will be very useful to evaluate efficacy of vaccines against the Lyme agent and the effect of antibiotic therapy on horses infected with B. burgdorferi.     

Evaluation of the efficacy of doramectin against an artificial infection of Dictyocaulus viviparus in calves

Three groups of eight Friesian calves, reared parasite-free, were experimentally infected with 1000 infective larvae of Dictyocaulus viviparus. Two groups were injected subcutaneously with 1% doramectin at 0.2 mg/kg body weight, one group 5 days after infection and the other 25 days after infection. A third group served as untreated controls. Faecal samples were examined for lungworm larvae on days 28, 32, 33, 34 and 35 after infection; the calves were killed and necropsied 39 or 40 days after infection and any lungworms present recovered and counted. Doramectin proved 100% effective against both 5-day-old and mature D. viviparus infections.     

Rabbit haemorrhagic disease: an investigation of some properties of the virus and evaluation of an inactivated vaccine.

An inactivated vaccine against rabbit haemorrhagic disease (RHD), developed and tested in our laboratory, is produced commercially by Bioveta, Ivanovice, Czechoslovakia. Rabbits developed full protection against infection 3 weeks after the administration of a single dose. Antibodies were detectable from day 5 after vaccination. Naturally acquired antibodies were demonstrated in some rabbits kept on commercial farms. The virus survived at least 225 days in an organ suspension kept at 4 degrees C, at least 105 days in the dried state on cloth at room temperature (around 20 degrees C), and at least 2 days at 60 degrees C, both in organ suspension and in the dry state. Experimental infection of rabbits younger than 2 months was successful in some animals. Hares, guinea pigs, white mice, golden and Chinese hamsters, chinchillas and hysterectomy-derived, colostrum-deprived piglets were resistant to infection.