Disodium-fosfomycin pharmacokinetics and bioavailability in post weaning piglets

Disodium-fosfomycin pharmacokinetics has been studied in different species after oral, intravenous, intramuscular and subcutaneous administration. At present there are neither documented clinical experiences of the use of fosfomycin in pigs nor any published studies in weaning piglets, although it is a period of high incidence of infectious diseases. The pharmacokinetics and the bioavailability of sodium fosfomycin were studied in post weaning piglets after intravenous and intramuscular administration of 15 mg/kg of body weight. Plasma concentrations were measured by a high-performance liquid ms/ms. After IV administration the area under the fosfomycin concentration:time curve in plasma was AUC_(0–12) of 120.00 ± 23.12 μg h/ml and the volume of distribution (Vd) of 273.00 ± 40.70 ml/kg. The elimination was rapid with a plasma clearance of 131.50 ± 30.07 ml/kg/h and a T_1/2 of 1.54 ± 0.40 h. Peak serum concentration (C_max), T_max, AUC_(0–12) and bioavailability for the IM administration were 43.00 ± 4.10 μg/ml, 0.75 ± 0.00 h, 99.00 ± 0.70 μg h/ml and 85.5 ± 9.90% respectively. Different authors have determined a minimum inhibitory concentration (MIC₉₀) ranging from 0.25 μg/ml for Streptococcus sp. and 0.5 μg/ml for Escherichia coli. Considering the above, and according to the values of plasma concentration vs time profiles observed in this study, effective plasma concentrations of fosfomycin for sensitive bacteria can be obtained following IV and IM administration of 15 mg/kg in piglets.     

Canine gastric dilatation-volvulus

Gastric dilatation-volvulus (GDV) is a dramatic and enigmatic disease of large and giant breed dogs characterised by the rapid accumulation of gas in the stomach. This causes gastric dilatation, twisting of the stomach about its long axis, compression of surrounding organs, hypovolaemic and cardiogenic shock, and if untreated, death. It has been estimated that the disease afflicts approximately 60,000 dogs in the USA each year with a mortality rate ranging from 7 to 60 per cent depending on accessibility to adequate veterinary care. The cause is unknown. While diet was at one time believed to be associated with the genesis of the disease, critical review of available data provides no evidence to support this hypothesis. A variety of predisposing or risk factors have been identified but none is suspected of being the cause, indeed, the disorder may have a multiple aetiology. Current thinking suggests that the final common pathway in the development of GDV may be an inhibition of gastric motility and emptying. This could come about through a primary disruption of normal gastric electrical patterns or through the effect of extraneous stressful events that disrupt gastric motility. After dilatation a series of potentially lethal events is unleashed which include compression of the caudal vena cava, pooling of blood in the microcirculation of the viscera and hindlimbs, metabolic acidosis, gastric necrosis, cardiac arrhythmias, disseminated intravascular coagulation, hypotensive and cardiogenic shock and death. Nevertheless, even advanced cases can survive if treated appropriately. If the cause could be identified logical prophylaxis might follow. Studies at the University of Florida have failed to demonstrate any effect of diet on gastric function in large breed dogs, suggesting that diet is probably not the cause of the disease. Researchers at Colorado State University also found no association with diet in clinical patients. Recent studies at the University of Florida have revealed distinct abnormalities in gastric electrical activity in GDV patients. In human patients these abnormalities, called dysrhythmias, have been associated with gastric distention, bloating, delayed emptying, nausea and retching. Unfortunately, dysrhythmias are also present, albeit to a lesser degree, in experimental GDV. These findings leave unanswered the question as to whether abnormalities in gastric motility play a role in the genesis of GDV.     

Extrahepatic biliary atresia in a border collie

Progressive lameness and leg pain were the predominant clinical signs in a 17-week-old male border collie presented for examination. On clinical investigation, extrahepatic cholestasis in association with rickets due to inadequate vitamin D resorption was diagnosed. The dog was treated parenterally with vitamin D and a cholecystoduodenostomy was performed. At 25 days postsurgery the lameness had resolved and bone structure was radiographically normal. However, at six weeks postsurgery, the dog's condition deteriorated rapidly and euthanasia was finally performed at eight weeks postsurgery. At postmortem examination, Toxocara canis nematodes were found to have invaded the biliary system via the anastomosis between the gallbladder and duodenum, causing biliary and hepatic toxocariasis. The cause of the primary extrahepatic cholestasis was atresia of the common bile duct at the hepatic end. The liver tissue showed microscopic lesions of chronic extrahepatic cholestasis as well as acute inflammation associated with the nematode invasion. There was no postmortem evidence of bone lesions. Extrahepatic biliary atresia is extremely rare in animals and has not been described before in dogs. In contrast, it represents the most common cause of congenital cholestasis in children, occurring in approximately one per 10,000 to 15,000 live births.     

Diagnosis of sporotrichosis in a donkey using direct fluorescein-labeled antibody testing.

A 4-year-old female donkey residing in an open field in Indiana was admitted for evaluation of facial lesions of 2 years duration. Cytologic and histologic examination of exudate and tissue from the lesions revealed a pyogranulomatous inflammatory reaction with numerous yeasts. Sporothrix schenckii was suspected to be the infectious agent; however, multiple culture attempts did not provide positive identification of the organism. Serologic examination supported infection with S. schenckii. A specific direct immunofluorescent antibody test performed on paraffin-embedded tissue sections confirmed the organism as S. schenckii. Clinical signs resolved after appropriate iodide therapy.     

AAHA senior care guidelines for dogs and cats

This paper provides a working framework for enhancing the well-being of senior pet dogs and cats. Approaches to screening the medical status of senior pets are described in detail, with particular emphasis on establishing baseline data in healthy animals, the testing of clinically ill animals, and assessing senior pets prior to anesthesia and surgery. The management of pain and distress and the application of hospice and palliative care are addressed. Advice on ways to approach euthanasia and dealing with end-of-life issues is also provided.     

Articular / epiphyseal osteochondrosis in Thoroughbred foals at 5 months of age: influences of growth of the foal and prenatal copper supplementation of the dam

AIMS: To determine the influence of copper (Cu) supplementation by injection of mares in late gestation on the frequency and severity of osteochondrosis (OC) lesions in their foals at around 160 days of age. To determine if there was any influence of the concentration of Cu in the liver, growth rate, birthweight, weight at 160 days of age, fatness, sex, or year of birth of the foal on the frequency and severity of OC lesions. To determine the influence of dam's age, and sex and birthweight of the foal on the growth rate from birth to 160 days of age, and weight at 160 days of age. METHODS: Thirty-three Thoroughbred foals, born in two consecutive years, were weighed every 2 weeks from birth. The dams had been supplemented with parenteral Cu or saline during late gestation, and the supplementation regimens were different in each year. Foals had liver biopsies harvested at birth for determination of Cu concentration. Pasture samples were collected every 4-8 weeks for analysis of concentration of Cu and zinc (Zn). At 160 days of age, articular cartilage of long bones was examined. Gross lesions were counted and scored, then sawn and radiographed, and processed for histopathology. Lesions were given radiographic scores and histopathological scores. Maximum scores for each lesion were combined to give a total OC score for each joint and each foal. The fatness of 20 foals (10 each from Years 1 and 2) at 160 days of age was determined chemically. RESULTS: Supplementation of dams with Cu had no significant effect on the concentration of Cu in the liver of foals at birth, or on the frequency or severity of lesions in articular cartilage at 160 days of age. The Cu and Zn concentrations of pasture were similar in Years 1 and 2, and were lower than current recommendations. All foals in Year 2, and 9/10 foals in Year 1 had irregularities in cartilage that was confirmed histologically to be indicative of OC. The average number of lesions per foal was 4.7 (SD 1.1) and 5.7 (SD 1.1) in Years 1 and 2, respectively. However, the severity of the lesions was considered mild, and no foals showed any clinical evidence of OC while alive. The number of lesions in the tarsocrural (TC) joint and the TC OC score at 160 days were positively associated with average daily weight gain (ADG) in the previous 4 weeks (p=0.005 and p=0.001, respectively). There was no significant effect of sex, fatness, birthweight, weight at 160 days of age, or year of birth of the foal on the frequency and severity of OC lesions. CONCLUSIONS: Many of the lesions classified as OC, using classification systems described by other authors, were likely to be normal variations of the process of endochondral ossification. Despite the high frequency of such lesions, they were considered to be of minor significance and none were clinically evident. The distribution of lesions was not typical, and most probably reflected the subtlety of the lesions. These results support the hypothesis that Cu is an over-emphasised factor in the aetiopathogenesis of OC. The relationship between subtle macroscopic lesions and lesions resulting in clinical signs of disease requires further investigation.     

Inhibitory effects of the beta-adrenergic receptor agonist zilpaterol on the LPS-induced production of TNF-alpha in vitro and in vivo

In this study the anti-inflammatory properties of zilpaterol, a beta2-adrenergic receptor (AR) agonist specifically developed as a growth promoter in cattle were investigated. Although zilpaterol has a different structure compared with the beta2-AR agonists known to date, it was noted that it was able to bind to both the beta2-AR (Ki = 1.1 x 10(-6)) and the beta1-AR (Ki = 1.0 x 10(-5)). Using lipopolysaccharide (LPS)-exposed U937 macrophages, the production of cyclic adenosine-3',5'-cyclic monophosphate (cAMP) and tumor necrosis factor alpha (TNF-alpha) were investigated. Zilpaterol inhibited TNF-alpha release and induced intracellular cAMP levels in a dose-dependent manner. The inhibition of TNF-alpha release and induction of cAMP production was mainly mediated via the beta2-AR, as indicated by addition of beta1- and beta2-specific antagonists. The effects of zilpaterol were investigated in LPS-treated male Wistar rats after pretreatment with zilpaterol. Zilpaterol dosed at 500 microg/kg body weight reduced the TNF-alpha plasma levels. In conclusion, zilpaterol is a beta2-adrenergic agonist and an inhibitor of TNF-alpha production induced by LPS both in vivo and in vitro.     

Complex Carbohydrates Occurring in the Digestive Apparatus of Umbrina Cirrosa (L.) Fry

The glycosoaminoglycans in the digestive apparatus of immature fish have important biological functions and are involved in morphofunctional differentiation. The aim of this study was to investigate the glycoconjugate histochemistry in the different parts of the digestive apparatus (oesophagus, stomach, intestine) of Umbrina cirrosa (L.) fry using classical histochemical reactions (periodic acid-Schiff, Alcian blue pH 2.5, Alcian blue/periodic acid-Schiff, high iron diamine, low iron diamine) in conjunction with glycolytic digestions that degrade different classes of glycosoaminoglycans. No differences were observed in the reactivity to conventional histochemical staining of the oesophagus, stomach or intestine among 27-, 34- or 44-day-old fry. In the oesophagus, the mucopolysaccharides contained chondroitin sulphates B and A and/or C, heparan sulphate and chondroitin. In the stomach, only neutral glycoconjugates were revealed, whereas in the intestine there were only chondroitin sulphates. Some differences in the type and content of glycoconjugates were found in Umbrina cirrosa (L.) fry compared to those of adult subjects, probably related to different dietary habits and to changes in the environmental conditions.     

Validation of the FAMACHA eye color chart for detecting clinical anemia in sheep and goats on farms in the southern United States

Recent studies on sheep and goat farms in the southern United States indicate that multiple-anthelmintic resistance in Haemonchus contortus is becoming a severe problem. Though many factors are involved in the evolution of resistance, the proportion of the parasite population under drug selection is believed to be the single most important factor influencing how rapidly resistance develops. Therefore, where prevention of resistance is an important parallel goal of worm control, it is recommended to leave a portion of the animals untreated. Recently, a novel system called FAMACHA was developed in South Africa, which enables clinical identification of anemic sheep and goats. When H. contortus is the primary parasitic pathogen, this system can be applied on the farm level to reduce the number of treatments administered, thereby increasing the proportion of the worm population in refugia. Since most studies validating the FAMACHA method have been performed in South Africa, it is important that the method be tested in other regions before its use is broadly recommended. We performed a validation study of FAMACHA by testing the system in sheep (n = 847) and goats (n = 537) of various breeds and ages from 39 farms located in Arkansas, Georgia, Louisiana, Florida, and the US Virgin Islands. The color of the ocular conjunctiva of all animals were scored on a 1-5 scale using the FAMACHA card, and blood samples were collected from each animal for determination of packed cell volume (PCV). Fecal samples were also collected from a majority of the animals tested for performance of fecal egg counts (FEC). Correlations between PCV and eye scores, PCV and FEC, and FEC and eye scores were all highly significant for both sheep and goats (P < 0.001). Data for both FAMACHA scores and PCV were evaluated using two separate criteria for anemia: eye score values of 3, 4 and 5 or 4 and 5, and PCV values of < or =19 or < or =15 were considered anemic. Specificity was maximized when eye score values of 4 and 5 were considered anemic and PCV cut off for anemia was < or =19, but sensitivity was low. In contrast, sensitivity was 100% for both sheep and goats when eye score values of 3, 4 and 5 were considered anemic and PCV cut off was < or =15, but specificity was low. In both sheep and goats, predictive value of a negative was greater than 92% for all anemia and eye score categories, and was greater than 99% for both eye score categories when an anemia cutoff of < or =15 was used. Predictive value of a positive test was low under all criteria indicating that many non-anemic animals would be treated using this system. However, compared to conventional dosing practices where all animals are treated, a large proportion of animals would still be left untreated. These data indicate that the FAMACHA method is an extremely useful tool for identifying anemic sheep and goats in the southern US and US Virgin Islands. However, further studies are required to determine optimal strategies for incorporating FAMACHA-based selective treatment protocols into integrated nematode control programs.