The behaviour of healthy awake cats following intravenous and intramuscular administration of midazolam

The onset of action and behavioural effects following intravenous (i.v.) and intramuscular (i.m.) administration of 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg of midazolam were studied for 2 h in 20 awake, healthy cats. All cats, except one that received 0.05 mg/kg i.m., showed effects of the drug, whereas no effects were observed in cats administered only the vehicle in which midazolam was dissolved. The onset of action was rapid following both i.v. and i.m. administration, some cats became ataxic, while others assumed positions of sternal or lateral recumbency. Even after administration of the highest dose (5.0 mg/kg), anaesthesia was not induced, with swallowing reflexes and conscious perception of a clamp placed on the tail still present in all cats. An abnormal arousal state was observed in many cats after administration of midazolam. During the first hour, restlessness was more commonly observed, while from 1 to 2 h, sedation was more prominent in cats that received the highest dose. Ataxia occurred in all but one cat, was short-lived in cats that received the lower doses, but still present at 2 h in all cats that received 2.0 and 5.0 mg/kg. Midazolam caused some of the cats to behave differently when approached and restrained compared with behavioural patterns identified prior to administration of the drug. The cats were more likely to behave abnormally following i.v. administration rather than i.m. administration and, for the most part, abnormal behaviour was equally distributed between the two extremes; cats being easier to approach and restrain and cats being more difficult to approach and restrain. Food consumption increased significantly, during the 2 h period, following all i.m. doses and all but the highest (5.0 mg/kg) i.v. dose, with most of the food being consumed in the first hour after administration.     

Effects of porcine relaxin on induced parturition in beef heifers

Two-year-old crossbred beef heifers were used to test the effects of porcine relaxin (pRelaxin) alone, or in combination with dexamethasone, on the induction of parturition, the incidence of dystocia, and retained placentas. Effects of treatment on pelvic area, postpartum interval, milk production, colostrum quality, calf birth weight, calf vigor, and calf performance were also evaluated. On Day 275 of gestation, heifers from two fetal-sire groups were randomly assigned to one of four groups in a 2 × 2 factorial design and received: no treatment (controls, N = 19), 20 mg of dexamethasone intramuscularly (im) (n = 22), 5 mg of pRelaxin (3,000 U/mg) im (n = 19), or 20 mg of dexamethasone plus 5 mg of pRelaxin (n = 17). Length of gestation (in days) was less (P < 0.05) in heifers treated with dexamethasone (279.8 ± 1.0) than in controls (286.6 ± 0.9), but was not influenced (P > 0.05) by treatment with pRelaxin. The incidence of retained placentas in heifers treated only with dexamethasone (27.3%) was not reduced by concomitant treatment with pRelaxin (35.3%). Retained placentas were not observed in any control heifers and in only one heifer (5.2%) treated solely with pRelaxin. Ease of calving (1 = unassisted, 5 = abnormal presentation) was not influenced by treatment (P > 0.05), even though birth weights (in kilograms) of calves from heifers treated with dexamethasone (36.4 ± 0.8) were less (P < .01) than those of calves from nondexamethasone-treated heifers (39.2 ± 0.8). Dexamethasone tended to reduce (P < 0.07) calf vigor (1 = healthy and strong, 5 = dead on arrival; 1.48 ± 0.11 vs. 1.18 ± 0.11), but was not (P > 0.05) influenced by pRelaxin. The duration of the postpartum anestrous interval (73.1 ± 1.8 d across groups) and pelvic areas following treatment and parturition were not influenced (P > 0.05) by dexamethasone or pRelaxin. Although determinants of colostrum quality (P < 0.01) and quantity (P < 0.08) of milk produced were influenced by dexamethasone, adjusted 205-d weights of calves did not differ (P > 0.05) among groups. In conclusion, treatment with pRelaxin alone failed to induce parturition or, when combined with dexamethasone, to reduce the incidence of retained placentas.     

Performance of broiler chicks fed on alkali‐treated neem (Azadirachta indica) kernel cake as a protein supplement

1. An experiment was conducted to evaluate growth and nutrient efficiency of broiler chicks from 3 to 42 d fed on diets containing alkali‐treated neem (Azadirachta indica A. juss) kernel cake (NKC) as a protein supplement in place of peanut meal (PNM).

2. NKC was treated with sodium hydroxide at 10 (ANKC 1) or 20 g (ANKC 2)/kg and incorporated into the test diets at 135 or 300 g/kg to replace 50 (low—L) or 100 (High—H) % of the PNM protein of the reference diet.

3. Despite comparable retentions of dry matter and total carbohydrate on L‐ANKC 1 and 2, fibre on L‐and H‐ANKC 2 and nitrogen, calcium and acid detergent fibre on all experimental diets compared to the retentions of chicks on the reference diet, only the chicks fed L‐ANKG 2 were found to grow and utilise food as well as those on the reference diet.

4. The activities of serum alkaline phosphatase on H‐ANKC 1 and alanine amino transferase on all test diets were depressed (P < 0.05), but the activity of serum aspartate amino transferase, total erythrocyte count and concentration of blood haemoglobin and urea were similar in all chicks.

5. No significant differences were noticed in the qualitative and quantitative characteristics of the meat of chicks fed on the reference diet and on diets incorporating ANKC at the lower concentrations. Feeding ANKC protein did not impart any untoward taste as evaluated in pressure cooked meat by a semitrained panel on a 7 point Hedonic scale.

6. Except for duodenal and jejunal inflammation in chicks on both reference and test diets, all the vital organs were normal, ruling out any adverse affects caused by residual neem bitters.

7. Comparable performance and cost of chicks fed on the reference and L‐ANKC 2 diets, warrants the utilisation of hitherto wasted protein‐rich NKC after alkali treatment in broiler chick diets to spare peanut meal for human consumption in developing countries.     

Ongoing Activity of Toscana Virus Genotype A and West Nile Virus Lineage 1 Strains in Turkey: A Clinical and Field Survey

Toscana virus (TOSV), West Nile virus (WNV) and tickborne encephalitis virus (TBEV) are among major viral pathogens causing febrile disease and meningitis/encephalitis. The impact of these viruses was investigated at a referral centre in Ankara Province, Central Anatolia in 2012, where previous reports suggested virus circulation but with scarce information on clinical cases and vector activity. Serum and/or cerebrospinal fluid samples from 94 individuals were evaluated, in addition to field‐collected arthropod specimens that included 767 sandflies and 239 mosquitoes. Viral nucleic acids in clinical samples and arthropods were sought via specific and generic nested/real‐time PCRs, and antibody responses in clinical samples were investigated via commercial indirect immunofluorescence tests (IIFTs) and virus neutralization. A WNV antigen assay was also employed for mosquitoes. WNV neuroinvasive disease has been identified in a 63‐year‐old male via RNA detection, and the WNV strain was characterized as lineage 1. TOSV infections were diagnosed in six individuals (6.3%) via RNA or IgM detection. Partial sequences in a 23‐year‐old female, presented with fever and transient pancytopenia, were characterized as TOSV genotype A. Febrile disease with arthralgia and/or peripheral cranial nerve involvement was noted in cases with TOSV infections. Previous WNV and TOSV exposures have been observed in 5.3% and 2.1% of the subjects, respectively. No confirmed TBEV exposure could be identified. Morphological identification of the field‐collected mosquitoes revealed Culex pipiens sensu lato (74.4%), Anopheles maculipennis (20.9%), An. claviger (2.1%) and others. Sandfly species were determined as Phlebotomus papatasi (36.2%), P. halepensis (27.3%), P. major s. l. (19.3%), P. sergenti (8.9%), P. perfiliewi (4.4%), P. simici (2.6%) and others. Viral infections in arthropods could not be demonstrated. TOSV genotype A and WNV lineage 1 activity have been demonstrated as well as serologically proven exposure in patients. Presence of sandfly and mosquito species capable of virus transmission has also been revealed.     

A Large‐scale,Rapid Public Health Response to Rabies in an Organ Recipient and the Previously Undiagnosed Organ Donor

This article describes and contrasts the public health response to two human rabies cases: one organ recipient diagnosed within days of symptom onset and the transplant donor who was diagnosed 18 months post‐symptom onset. In response to an organ‐transplant‐related rabies case diagnosed in 2013, organ donor and recipient investigations were conducted by multiple public health agencies. Persons with potential exposure to infectious patient materials were assessed for rabies virus exposure. An exposure investigation was conducted to determine the source of the organ donor's infection. Over 100 persons from more than 20 agencies spent over 2700 h conducting contact investigations in healthcare, military and community settings. The 564 persons assessed include 417 healthcare workers [5.8% recommended for post‐exposure prophylaxis (PEP)], 96 community contacts (15.6% recommended for PEP), 30 autopsy personnel (50% recommended for PEP), and 21 other persons (4.8% recommended for PEP). Donor contacts represented 188 assessed with 20.2% recommended for PEP, compared with 5.6% of 306 recipient contacts recommended for PEP. Human rabies cases result in substantial use of public health and medical resources, especially when diagnosis is delayed. Although rare, clinicians should consider rabies in cases of encephalitis of unexplained aetiology, particularly for cases that may result in organ donation.     

Pharmacokinetics and pharmacodynamics of glycopyrrolate following a continuous‐rate infusion in the horse

Glycopyrrolate (GLY) is an antimuscarinic agent that is used in humans and domestic animals primarily to reduce respiratory tract secretions during anesthesia and to reverse intra‐operative bradycardia. Although GLY is used routinely in veterinary patients, there is limited information regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties in domestic animals, and an improved understanding of the plasma concentration–effect relationship in racehorses is warranted. To accomplish this, we characterize the pharmacokinetic–pharmacodynamic (PK‐PD) actions of GLY during and after a 2‐h constant‐rate intravenous infusion (4 μg/kg/h) and evaluate potential PK‐PD models for cardiac stimulation in adult horses. Measurements of plasma GLY concentrations, heart and respiration rates, and frequency of bowel movements were performed in six Thoroughbred horses. The time course for GLY disposition in plasma followed a tri‐exponential equation characterized by rapid disappearance of GLY from blood followed by a prolonged terminal phase. Physiological monitoring revealed significant (P < 0.01) increases in heart (>70 bpm) and respiratory rates accompanied by a marked and sustained delay in the frequency of bowel movements (1.1 ± 0.2 h [saline group] vs. 6.0 ± 2.0 h [GLY group]). Two of six horses showed signs of colic during the 8‐h observation period after the end of the GLY infusion, but were treated and recovered without further complications. The relationship between plasma GLY concentration and heart rate exhibited counterclockwise hysteresis that was adequately described using an effect compartment.     

Feed intake and serum GH, LH and cortisol in gilts after intracerebroventricular or intravenous injection of urocortin

In three experiments (Exp), ovariectomized gilts received intracerebroventricular (ICV; Exp 1 - with restraint, Exp 2 - without restraint) or intravenous (i.v.; Exp 3) injections of urocortin or saline to assess effects on feed intake and serum GH, LH, and cortisol. Following a 20-hr fast, feed was presented at 1 hr (Exp 1) or 30 min (Exp 2 and 3) after injection (time = 0 hr) of saline or 5 (U5) or 50 (U50) μg/pig (Exp 1 and 2) or 5 μg/kg BW (Exp 3) of urocortin. Blood samples were collected every 15 min from –2 to 6 hr relative to injection and hormone data pooled 2 hr before and hourly after treatment. Treatment with U50 decreased feed intake, relative to saline (treatment x time interaction; P < 0.05), when delivered ICV but not i.v. A treatment by time interaction was detected for GH (Exp 1, 2, 3) and LH (Exp 1 and 2; P < 0.01). Serum GH increased over time (relative to −2 hr; P < 0.05) following treatment with urocortin but not saline regardless of route of administration. Conversely, in Exp 1 (U5 and U50) and Exp 2 (U50), LH decreased relative to −2 hr with a delayed decrease during Exp 1. Serum cortisol was not affected by treatment in Exp 1, but increased following urocortin in Exp 2 and 3 (treatment by time interaction, P < 0.01). These data provide evidence that urocortin modulates GH and LH concentrations and suppresses feed intake in gilts via mechanisms which may be independent of cortisol and may depend upon dose and route of administration.     

Anticoccidial Vaccination of Broiler Chickens in Various Management Programmes: Relationship between Oocyst Accumulation in Litter and the Development of Protective Immunity

Paracox anticoccidial vaccine was administered to a 7-day-old flock of commercial broiler breeder stock subsequently reared to point-of-lay in the same house. For comparison, three subgroups of another flock of broiler breeders were also vaccinated with Paracox at 7 days of age, reared to 42 days and then transferred to new litter on another farm until point-of-lay. The first subgroup received no further treatment, but the second and third each received a second vaccination with Paracox, either immediately after transfer to the new litter or 42 days after transfer. Using an Eimeria necatrix model, protective immunity was demonstrated by virulent challenge of samples of birds from all groups by the age of 37–40 days (30–33 days after the first vaccination), and was maintained to at least 122–125 days of age, whether the birds remained on the same litter or were transferred to another farm, and whether they received one or two anticoccidial vaccinations. Therefore, there is no disadvantage in transferring birds onto new litter 35 days after a single Paracox vaccination, nor is there any advantage in giving a second vaccination after such a transfer. Vaccinated birds seeded the new litter with oocysts, despite being clinically immune to coccidiosis. A supplementary laboratory experiment showed that birds vaccinated at 8 days of age passed almost no oocysts after a second vaccination at 43 days of age. This indicated that they were not only protected against clinical coccidiosis, but were almost solidly immune to a homologous infection 5 weeks after a single vaccination. Nevertheless, oocysts appeared in the litter of all four groups of commercial breeders throughout the trial, showing that wild-type heterologous infections occurred whether the birds were transferred to new litter or not, but these did not overwhelm the acquired protective immunity and cause clinical coccidiosis.