Pharmacokinetics of phenylbutazone in two age groups of ponies: a preliminary study

A clinical dose rate (4.4 mg/kg bodyweight) of phenylbutazone was administered intravenously and orally to six Welsh mountain ponies to provide data on the pharmacokinetics and bioavailability of the drug. In three, three-year-old ponies, clearance of the drug from plasma after intravenous administration was almost twice as rapid as in three ponies aged eight to 10 years. After oral administration, plasma phenylbutazone levels were greater in the older ponies, the area under the plasma concentration time curve being almost twice as high. This did not result from more efficient absorption but from slower plasma clearance. The fractional absorption of phenylbutazone was similar in young and older ponies, 0.78 and 0.75, respectively. The 24 hour urinary excretion of phenylbutazone and its hydroxylated metabolites, oxyphenbutazone and gamma-hydroxyphenylbutazone, accounted for approximately 25 per cent of the administered intravenous dose in both young and older ponies. The possible fate(s) of the remaining 75 per cent were considered.     

An immunodeficiency in Fell ponies: a preliminary study into cellular responses.

A putative immunodeficiency, causing mortality in UK Fell pony foals (Fell pony syndrome), was studied in affected foals and compared with healthy, age-matched foals. Differential cell counts of peripheral blood indicated that the syndrome foals were lymphopenic (P<0.05). Flow cytometric analysis of circulating leucocytes showed a reduced MHC II expression (P<0.01) on lymphocytes but not on polymorphonuclear cells in affected foals. There were no changes in the percentages of CD4+ or CD8+ T cells. There was an increased (P<0.05) expression of CD11a/18 by the lymphocytes of the syndrome foals, compared to the control foals, which is probably a response to systemic bacterial infections. The syndrome foals' lymphocytes responded to mitogens (PHA, ConA, PWM) at normal levels. The data do not conform to any known immunodeficiencies identified in any other species. Further analyses will be required, particularly on bone marrow function.     

Dientamoeba fragilis in swine population: a preliminary investigation

Dientamoeba fragilis, a protozoan with worldwide distribution is considered to be responsible for enteric disease in humans. A wide spectrum of clinical symptoms including; diarrhoea (acute or prolonged), flatulence, abdominal pains and other unspecific bowel symptoms have been ascribed to this parasite. Asymptomatic infection has also been reported. Dientamoeba fragilis is as its name indicates an extremely delicate protozoon and only the trophozoite has ever been demonstrated in stool samples. The definitive diagnosis of this infection is based on demonstration in permanently stained stool samples. In Italy examination of ova and parasite (O&P) samples are not currently performed. This protozoan is extremely difficult to cultivate but molecular techniques such as the Polymerase Chain Reaction offer promise as a means of diagnosing infection. The epidemiology of Dientamoebiasis is not clear. This paper will present preliminary results from a study looking for the parasite's presence in swine faeces. The possible role of pigs as a reservoir of infection was studied; 121 faecal samples from breeding and fattening pigs were examined using a Giemsa permanent stain. Dientamoeba fragilis was found in 53 (43.8%) of the stool samples examined.     

Felinine excretion in domestic cat breeds: a preliminary investigation

The aim of this study was to determine possible differences in felinine excretion between domesticated cat breeds. For this purpose, urine was collected from a total of 83 privately owned entire male cats from eight different breeds in the Netherlands during the period of November 2010 till November 2011. In the collected samples, free felinine and creatinine concentrations were measured. Free felinine concentrations were expressed relative to the urinary creatinine concentration to compensate for possible variations in renal output. The mean (±SD) felinine:creatinine (Fel:Cr) ratio as measured over all cats was 0.702 (±0.265). Both the Abyssinian and Sphynx breeds showed the highest Fel:Cr ratio (0.878 ± 0.162 and 0.878 ± 0.341 respectively) which significantly differed from the ratios of the British Shorthairs (0.584 ± 0.220), Birmans (0.614 ± 0.266), Norwegian Forest cats (0.566 ± 0.296) and Siberian cats (0.627 ± 0.124). The Fel:Cr ratios of the Persians (0.792 ± 0.284) and Ragdolls (0.673 ± 0.256) showed no statistical difference with either of the other breeds. A significant proportion of the observed variation between the different feline breeds could be explained by hair growth, as both hair growth and felinine production compete for available cysteine. Shorthaired and hairless cat breeds generally showed a higher Fel:Cr ratio compared to longhaired cat breeds, with the exception of Persian cats. Further research is warranted to more closely study the effect of hair growth on felinine production.     

Equine thyroid function tests: a preliminary investigation.

A similar and significant (P less than 0.001) increase in plasma thyroxine (T4) concentration was seen in seven clinically normal thoroughbred horses 2 h after the intravenous administration of either 2.5 iu or 5 iu of thyroid stimulating hormone (TSH) with a peak response around 4 h after administration. The intravenous administration of 0.2, 0.5 or 1 mg thyrotrophin releasing hormone (TRH) resulted in a significant (P less than 0.01) increase in T4 concentration in three groups of animals; six thoroughbreds in full work, five thoroughbreds at rest and four ponies at rest. The peak response was recorded at 3 or 4 h after administration. A significant difference between the groups in the degree of response to TRH was only found between the thoroughbreds in work and those at rest with 1 mg TRH (P less than 0.05). When two additional ponies were investigated in a similar way, a reduced response to TRH was observed: a pregnant mare had a similar response to 5 iu TSH as the thoroughbreds; the other pony also showed a lowered response to TSH. In a group of 2- or 3-year-old thoroughbreds in training no difference in the T4 response 4 h after intravenous administration of 0.5 mg TRH could be determined, according to the month, age, sex or work intensity. Although resting T4 concentrations did not differ significantly between animals believed to be suffering from the equine rhabdomyolysis syndrome (ERS) and those suffering from a variety of other conditions, some ERS sufferers may have a lowered response to TRH.     

Use of a wireless system to measure invasive arterial blood pressure in ponies – preliminary study

Objective  To evaluate the feasibility and functionality of intra-carotid wireless device implantation in ponies, and to investigate its short-term complications.
Study design  Prospective preliminary study.
Animals  Five mixed breed, adult, intact male ponies weighing 104 ± 28.8 kg (mean ± SD) underwent surgery. Arterial blood pressure data were continuously collected from four animals.
Methods  General anesthesia was induced on two consecutive days. On the first day, an intra-arterial wireless device was implanted in the right carotid artery. On the next day, a transcutaneous intra-arterial catheter was placed in the left facial artery. Data from both sources were collected. Post-mortem examination was performed.
Results  Surgical time was 27.1 ± 11.85 minutes. All catheters remained in place with some extra vascular migration. Complications included mild seroma and hematoma.
Conclusion  The wireless system allowed continuous monitoring in ponies throughout anesthesia and at rest and may allow for the recording of arterial blood pressure and heart rate when it would be difficult to achieve with a conventional system (e.g. during recovery from anesthesia).
Clinical relevance  The wireless invasive blood pressure monitor may allow continuous measurements when only intermittent measurements would be feasible with a wired system.     

Mucosal permeability of water-soluble drugs in the equine jejunum: a preliminary investigation

Ussing chambers have been used to study the mucosal permeability of drugs in humans, rats and other species. This data can then be used to develop in vitro/in vivo correlations (IVIVC) for drugs based on the Biopharmaceutics Classification System (BCS). Due to the poor oral bioavailability of many drugs in the horse, this method may be useful for screening drugs before development to determine if they warrant further study. Cephalexin (CPX), marbofloxacin (MAR), metronidazole (MTZ) and fluconazole (FCZ) were chosen for this study based on the wide range of physicochemical properties and bioavailability in the horse. Permeability was ranked as follows: MTZ > FCZ > MAR > CPX. This correlated with the bioavailability (R(2) = 0.633447), the Log P (R(2) = 0.648517), as well as the molecular weight (R(2) = 0.851208) of the drugs. Metronidazole induced a decrease in the tissue transepithelial resistance, suggestive of the possibility of tissue toxicity, which may have falsely increased its permeability. The low permeability of cephalexin across the tissue may indicate a lack of active transporters that are found in other species. From this study, we can conclude that the Ussing chamber is a promising method for determining mucosal permeability in the horse.     

A preliminary report on a fat-free diet formula for nasogastric enteral administration as treatment for hyperlipaemia in ponies.

A fat-free liquid diet was formulated to be administered by nasogastric tube as therapy for hyperlipaemia in ponies. The liquid diet provided energy, protein, minerals, trace elements, and vitamins in accordance with the requirements of ponies. As sole source of nutrition, the liquid diet fully counteracted fasting-induced hyperlipaemia in two healthy ponies. The liquid diet was also used in hyperlipaemic patients, but only in combination with conventional therapy, consisting of intravenous administration of glucose, insulin, and heparin. Although no patients were treated with the liquid diet alone, the liquid diet has potential in the treatment of hyperlipaemia - it is easy to prepare and to administer by nasogastric tube and it provides energy and nutrients to counteract the negative energy balance and low nutritional status of patients. Experience is needed with hyperlipaemic patients that are treated with the liquid diet only.     

Assessment of the rate of solid-phase gastric emptying in ponies by means of the 13C-octanoic acid breath test: a preliminary study

The aim of this study was to assess the feasibility of applying the 13C-octanoic acid breath test for assessment of gastric emptying in ponies by investigating the pattern of 13C enrichment in breath following the administration of a test meal +/- 13C-octanoic acid. After a 14 h fast, the ponies received either no meal (Test I) or a standardised test meal labelled with 0 mg (Test II), 125 mg (Test III), 250 mg (Test IV) or 500 mg (Test V) 13C-octanoic acid. For each test (I-V), exhaled breath samples were collected in duplicate at 1 h and immediately before ingestion of the test meal and at frequent intervals thereafter for 12 h. Breath samples were analysed by continuous flow isotope ratio mass spectrometry. Three indices of breath 13C-enrichment were computed; half dose recovery time (t1/2), gastric emptying coefficient (GEC) and time to peak breath 13C-enrichment t(max). For Tests I and II, the ratio of 13CO2:12CO2 remained stable for the duration of the sampling period. For Tests III, IV and V, an increase in the ratio of 13CO2:12CO2 was detected. The test was reproducible within individuals, and intersubject variation was low. Further validation studies of this noninvasive technique are justified.     

Cephalexin: interpretation of sensitivity disc testing in veterinary practice

A regression study using 30 micrograms cephalexin sensitivity discs with bacterial strains isolated from veterinary sources is described. Techniques suitable for use in veterinary investigation laboratories were used and critical zone sizes calculated from a linear regression analysis. Zone sizes of less than or equal to 18 mm, 19 to 20 mm and greater than or equal to 21 mm were found to be suitable to categorise strains as resistant, intermediate or sensitive, respectively. Experience in the use of these recommended critical zone sizes in clinical practice will be necessary before firm recommendations can be made.     

Phenylbutazone toxicity in ponies

The oral administration of phenylbutazone at a dose rate of approximately 10 mg per kg per day for seven to 14 days resulted in the development of signs of toxicity in seven of eight ponies treated. Clinical signs included anorexia, depression and abdominal oedema. Blood biochemical determinations showed a decrease in total plasma protein and calcium concentrations with an increase in urea concentration. These changes were considered indicative of water retention. Three of the ponies died during treatment following the development of shock. Shock was considered to arise from the submucosal oedema of the large intestine observed on necropsy. Oral ulceration was also found in these animals. In two ponies intravenous administration of phenylbutazone (4.0 mg per kg) for seven days was studied. In one of these ponies a marked decrease in total plasma protein concentration occurred.