Microbial composition affects the performance of an artificial Tephritid larval diet.

The present study investigated the patterns of microorganisms in an artificial larval diet during Dacus ciliatus (Diptera; Tephritidae) larval development. Microbial population contents in the diet of total heterotrophic bacteria, yeast and molds, coliform and lactobacilli, and their dynamics during development, were monitored. Initially, the microbial composition in diet trays failing to produce viable pupae and in trays successfully producing pupae and adult flies was characterized. The failing diet trays contained large populations of lactobacilli that increased during larval development, and low populations of coliforms. In contrast, the successful diet showed an increasing population of coliforms and a low, or undetected, population of lactobacilli. To study the hypothesis that lactobacilli affect D. ciliatus larval development, we conducted controlled inoculation experiments in which Lactobacillus plantarum was added into fresh diet at the time of egg seeding. L. plantarum inoculated trays showed no production of D. ciliatus. Control trays without lactobacilli inoculation showed variable results. One tray successfully produced viable pupae and adults, and showed a slight and slow increase in the indigenous populations of lactobacilli. The second tray, however, failed to produce pupae and showed a fast increase of the indigenous lactobacilli to very high levels. Monitored pH trends in L. plantarum-inoculated diet showed a sharp pH decrease during the first 4 days of larval development from 5 to less than 4 units, while successful diet, producing viable D. ciliatus pupae and adults, showed a moderate pH drop during most of the larval development period. The paper discusses the possible ecological interactions between D. ciliatus larvae, the microbial content of the diet and the physical properties of the diet. The discussion also points out at the usefulness of this approach in understanding and managing mass production parameters of tephritid fruit flies industrial diets used for Sterile Insect Technique.

Laboratory longevity and competitiveness of Dacus ciliatus Loew (Diptera: Tephritidae) following sub-sterilizing gamma irradiation.

The effect of a sub-sterilizing gamma radiation dose on Dacus ciliatus adults was investigated to assess the suitability of the sterile insect technique (SIT) as an alternative method to control this pest. Late pupae (48 h prior to adult emergence) from a laboratory strain were irradiated with 120 Gy of gamma rays emitted by a 60Co source. Following adult emergence, the mortality of irradiated and non-irradiated cohorts was recorded. Over a period of 50 days after emergence, no significant negative effects of irradiation upon the longevity of male or female laboratory flies were observed. A laboratory competitiveness study (Fried test), using irradiated laboratory and wild males at a ratio of 3:1 was conducted to assess the ability of irradiated males to reduce the egg hatch rates of a wild population. The overall competitiveness was found to be ca. 0.32, suggesting a reduced, but satisfactory, quality of irradiated laboratory as compared with wild males. Based on the above findings, we calculated and proposed effective male release ratios for field application of SIT against D. ciliatus.

Intravenous infusion of electrolyte solution changes pharmacokinetics of drugs: pharmacokinetics of ampicillin.

The pharmacokinetics of ampicillin in dogs was determined after intravenous (i.v.) bolus and constant rate infusion. Ampicillin was administered to six beagle dogs as an i.v. bolus at 20 mg/kg and as a constant rate i.v. infusion (CRI) at 20 mg/kg during 8 h (0.042 mL/min/kg) in Ringer's lactate (Hartmann's) solution. The concentrations were determined by an LC/MS/MS method. After i.v. bolus, ampicillin total body clearance, apparent volume of distribution at steady-state, mean residence time (MRT), and half-life were 4.53 ± 0.70 mL/min/kg, 0.275 ± 0.044 L/kg, 61 ± 13 min, and 111 (85-169) min, respectively. The corresponding parameters calculated after CRI were 13.5 ± 1.06 mL/min/kg, 0.993 ± 0.415 L/kg, 73 ± 27 min, and 49 (31-69) min. Ampicillin concentration decreased by 30% in the Ringer's lactate infusion solution mostly during the first hour after preparation of the solution. Constant rate infusion of Ringer's lactate solution during 8 h caused significant changes in ampicillin pharmacokinetics. The results suggested that special attention should be given to drug pharmacokinetics when co-administered intravenously with electrolyte solutions.

Use of the novel atypical opioid tapentadol in goats (Capra hircus): pharmacokinetics after intravenous, and intramuscular administration.

The objective of the present study was to assess the pharmacokinetics of the novel atypical drug tapentadol (TAP) after intravenous (I.V.) and intramuscular (I.M.) injections in clinically healthy goats. A 2 × 2 cross-over design study was carried out. Six local adult Nubian nonlactating, nonpregnant female goats, were given 5 mg/kg body weight of TAP by I.V. and I.M. routes. The concentrations of TAP in plasma were evaluated using a validated HPLC method. Transient adverse effects were noticed in some animals, especially after I.V. administration (tremors and ataxia). Three days after drug administration, severe hair loss was also recorded. The plasma concentrations after the two routes of administration were best described by a bi-compartmental model. After I.M. injection, TAP showed a very fast absorption (Tmax  = 0.17 h) and a short half-life (1.29 h). The I.M. bioavailability was quite high, despite being variable (87.8 ± 35.6%). This is the first pharmacokinetic study of TAP in goats but due to its unknown safety profile and efficacy, it is premature to recommend the use of this drug in clinical ovine practice.

Efficacy of antimicrobial and nutraceutical treatment for canine acute diarrhoea: A systematic review and meta-analysis for European Network for Optimization of Antimicrobial Therapy (ENOVAT) guidelines.

Systemic antimicrobial treatments are commonly prescribed to dogs with acute diarrhoea, while nutraceuticals (prebiotics, probiotics, and synbiotics) are frequently administered as an alternative treatment. The aim of this systematic review and meta-analysis was to assess the effectiveness of antimicrobials and nutraceutical preparations for treatment of canine acute diarrhoea (CAD). The results of this study will be used to create evidence-based treatment guidelines. PICOs (population, intervention, comparator, and outcome) were generated by a multidisciplinary expert panel taking into account opinions from stakeholders (general practitioners and dog owners). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty of the evidence. The systematic search yielded six randomised controlled trials (RCT) for antimicrobial treatment and six RCTs for nutraceutical treatment meeting the eligibility criteria. Categories of disease severity (mild, moderate, and severe) were created based on the presence of systemic signs and response to fluid therapy. Outcomes included duration of diarrhoea, duration of hospitalization, progression of disease, mortality, and adverse effects. High certainty evidence showed that antimicrobial treatment did not have a clinically relevant effect on any outcome in dogs with mild or moderate disease. Certainty of evidence was low for dogs with severe disease. Nutraceutical products did not show a clinically significant effect in shortening the duration of diarrhoea (based on very low to moderate certainty evidence). No adverse effects were reported in any of the studies.

European Network for Optimization of Veterinary Antimicrobial Therapy (ENOVAT) Guidelines for Antimicrobial Use in Canine Acute Diarrhoea.

Acute diarrhoea is a common presentation in dogs, and a common reason for antimicrobial prescription and nutraceutical use. This evidence-based guideline provides recommendations for antimicrobial and probiotic treatment of canine acute diarrhoea (CAD). A multidisciplinary panel developed the recommendations by adhering to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The opinions of stakeholders (general veterinary practitioners and dog owners) were collected and incorporated to ensure the applicability of this guideline. Four strong recommendations informed by high certainty evidence, and three conditional recommendations informed by very low or low certainty evidence, were drafted by the panel, along with an ungraded section on diagnostic work-up of dogs with acute diarrhoea. The ENOVAT guidelines initiative encourages national or regional guideline makers to use the evidence presented in this document, and the supporting systematic review, to draft national or local guidance documents.

Novel gastroretentive controlled-release drug delivery system for amoxicillin therapy in veterinary medicine.

Beta-lactam antimicrobials, commonly used in both veterinary and human medicine, generally present short biologic half-lives, whereas their activity is enhanced as pathogen exposure is prolonged. These properties necessitate multiple-dose regimens of standard dosage forms, thereby hampering pet owner adherence, frequently resulting in therapeutic failure. This study presents a novel controlled-release gastroretentive oral drug delivery system for beta-lactams with which single-dose administration provides an effective antimicrobial course, optimizing pharmacokinetic (PK)-pharmacodynamic (PD) profiles, minimizing adverse effects and emergence of antimicrobial resistance and facilitating adherence. Our prototype sustained-delivery swelling-tablet (SDST), based on a degradable hydrophilic polymeric matrix, was designed to enable continuous input of these drugs to their absorption sites over several days. Several SDST formulations of the beta-lactam amoxicillin were evaluated in in vitro dissolution studies. Two formulations were selected for further in vivo canine studies, for determination of gastric retention and PK-PD profiling. Prolonged gastric retention times maintaining allowed for maintained effective drug concentrations against many clinically relevant pathogens for more than 48 h for one formulation and more than 5 days for the other. Both SDST formulations offer significant advantages over standard immediate-release therapy in achieving PK-PD goals and enhancing adherence. The prototypical formulations represent a novel platform which may be modified to meet various clinical requirements.

A novel subcutaneous controlled-release amoxicillin degradable implant for extended-interval administration in veterinary medicine.

Dosage forms of antimicrobials play a critical role in facilitating the attainment of pharmacokinetic-pharmacodynamic (PK-PD) targets as well as adherence in both veterinary and human medicine. The purpose of this study was to develop and evaluate a controlled-release subcutaneous amoxicillin implant for single-dose therapy of large ruminants such as goats, sheep, and deer. The degradable implant, designed to attain PK-PD targets following single administration, was evaluated for amoxicillin release rate and time-concentration profile. In vitro release studies demonstrated constant-rate release of approximately 40% of amoxicillin content within 96 h. In an in vivo study in goats, serving as a model for target animals, a serum concentration of approximately 0.4 mg/L was achieved within 8 h of implant insertion and maintained for >6 days. In comparison, in control goats given a standard single intramuscular amoxicillin dose of 15 mg/kg, amoxicillin peaked at 1.2 mg/L after 1 h, rapidly dropping to below detection level at 8 h. These results suggest that the proposed implant offers a unique modality for animal caregivers to conveniently administer a full antimicrobial course following a single dose of an efficient PK-PD-optimized dosage form. Furthermore, modifications of implant composition may allow for tailoring of its characteristics to various PK, PD, microbiological, and clinical requirements.

Azithromycin concentration in severely inflamed canine external ear canals - a case series.

OBJECTIVE: To determine azithromycin concentration in severely inflamed canine external ear canals. MATERIAL AND METHODS: Five dogs of various breeds and ages with severe and chronic otitis externa underwent ear canal reconstruction surgery. A single oral dose of azithromycin at 10 mg/kg was administered 12 to 24 hours prior to surgery. Tissue samples were collected from the excised external ear canals and azithromycin concentration was determined using a liquid chromatography-tandem mass spectrometry method. RESULTS: Azithromycin concentrations ranging from 11.4 to 107.0 µg/g (mean 59.2 ± 44.6 µg/g, median 50.9 µg/g) were detected in the chronically infected external ear canal tissue 12 to 24 hours after administration. CLINICAL SIGNIFICANCE: Little information exists on antibiotic concentrations in pathological tissues of dogs. Macrolides are known to concentrate in skin tissue. In light of the present results, investigation of clinical efficacy of azithromycin in chronic canine otitis externa is warranted.

In vitro lectin binding to the outer surface of Spirocerca lupi at different life-stages.

Spirocerca lupi is the esophageal nematode of dogs. Early, transient eosinophilia occurs in experimentally infected dogs, but is absent in advanced cases, suggesting that the nematode evades the dog's immune system. Lectins are proteins or glycoproteins of plant or animal origin, binding different saccharides, with varying specificities and avidities, used to characterize surface haptens in plant and animal parasitic helminths. This study investigated the in vitro binding of six lectins (Concanavalin A [ConA], wheat germ agglutinin [WGA], peanut agglutinin [PNA], soybean agglutinin [SBA], Dolichus biflorus agglutinin [DBA] and Ulex earopaeus agglutinin I [UEA]) to the surface of S. lupi nematodes at different life stages, the L2 and L3 larvae (dead and alive) and to dead adult worms, with negative controls, with and without addition of the six respective inhibitory sugar haptens. Con A moderately bound to surfaces of both live and frozen L3, to the stoma and excretory pores of adult worms, and to the outer surface nematode's eggs, within a female worm, but not to L2. PNA bound only to stoma and excretory pores surfaces in both frozen and live L3. WGA bound strongly to the outer surfaces of live and dead L2 and L3, which resulted in molting of live larvae. These results suggest that the nematode's surface content change during its development. Such changes may play roles in the nematode's interactions with the intermediate and definitive hosts' tissues, and in its ability to evade the immune response, its long survival within the host, and even induce neoplastic transformation.

Long-term outcome of transendoscopic oesophageal mass ablation in dogs with Spirocerca lupi-associated oesophageal sarcoma.

Oesophageal sarcoma is a potential sequel of Spirocerca lupi infection. Oesophageal mass excision can be performed by open chest surgery. The objectives of this observational study were to evaluate the feasibility, short-term morbidity and long-term outcome of transendoscopic oesophageal mass ablation in dogs with spirocercosis-associated oesophageal neoplasia. A 9 mm video-endoscope and laser or electrocauterisation were used to debulk the oesophageal mass. Long-term follow-up was done by telephonic interviews. Fifteen dogs were included. The median tumour size was 5 cm (range 3.5-9). The median procedure time was 75 minutes (range 35-165) and was deemed successful in 12/15 dogs (80 per cent). Recovery was uneventful in all dogs. Immediate complications included oesophageal damage (two dogs) oesophageal perforation (one dog) and a focal thermal damage (one dog). The median hospitalisation time of all dogs was less than one day, with all but two discharged on the procedure day. The median survival time, available in nine dogs that were followed, was 202 days (range 51-691). Four of these dogs (44 per cent) survived more than six months, of which three survived more than one year. In conclusion, transendoscopic oesophageal mass ablation might be considered an alternative, palliative procedure for open-chest oesophageal surgery. It has comparable long-term survival, lower morbidity, short hospitalisation time and relatively low cost.

Attentional bias and spider phobia: conceptual and clinical issues.

Experimental evidence indicates that anxious subjects show an attentional bias for threat-relevant information. Foa and McNally (1986) (Cognitive Therapy and Research, 10, 477-485) and Watts et al. (1986) (British Journal of Psychology, 77, 97-108) reported that behaviour therapy can eliminate this attentional bias. A replication study was carried out in order to increase the evidence for exposure being the crucial component in reducing attentional bias. Moreover, in this study some conceptual and clinical issues are explored. The theoretical and clinical implications of the results are discussed.

Effects of matches and mismatches in agoraphobic and neutral situations.

An experiment was conducted to investigate the generalizability of Rachman's match/mismatch model and to explore if environmental conditions affect the consequences of an underprediction. Twenty subjects walked around in agoraphobic, and 15 did so in neutral, situations. Both groups carried a walkman and 7 aversive human screams were administered to them at random times. The results gave strong support to previous investigations on matches and mismatches, but no differences were shown between agoraphobic and neutral situations. Possible explanations are discussed.

Selective processing of emotional information in obsessive compulsive disorder.

Three possible explanations for attentional bias effects in anxious subjects have been formulated: the threat-relatedness hypothesis, the emotionality hypothesis and the concern-relatedness hypothesis. In order to investigate these three hypotheses, an experiment was carried out with 33 obsessive compulsive (OC) patients and 29 normal controls. Both groups colour-named a Stroop card with 5 word sets: neutral words and 4 emotional word sets (a 2 x 2 matrix of words, related/unrelated to obsessive compulsive disorder and positively/negatively valenced). In line with previous studies, OC patients selectively attended to negative OC-related cues; this supports the threat-relatedness hypothesis. Although the set-up of the experiment was similar to the Mathews and Klug (1993, Behaviour Research and Therapy, 31, 57-62) study, no evidence was found for the concern-relatedness hypothesis, i.e. the OC patients did not show an attentional bias for positive OC-related words. Two possible reasons for these contradicting findings are discussed.

Pharmacokinetics of ampicillin administered intravenously and intraosseously to kittens.

An aqueous solution of ampicillin sodium (100 mg ml-1) was administered intravenously and intraosseously to six kitten at 50 mg kg-1 in a crossover study. Jugular vein blood samples were taken at intervals up to eight hours after treatment and the serum ampicillin concentration-time data, derived from a microbiological assay, were analysed pharmacokinetically. The disposition kinetics of ampicillin administered by the two routes were very similar. The mean elimination half-life (t1/2 beta), the area-derived volume of distribution (Varea) and the total body clearance (ClB) values after the intravenous and intraosseous treatment were 86.3 and 79.0 minutes, 0.9 and 0.8 litre kg-1 and 7.3 and 7.6 ml min-1 kg-1, respectively. No side-effects related to the intraosseous administration of the drug were observed.

Spirocerca lupi in dogs: prophylactic effect of doramectin.

Spirocerca lupi is primarily a parasite of dogs, which typically causes oesophageal nodules, aortic aneurysms, and spondylitis. This study investigated the efficacy of doramectin as a prophylactic agent for canine spirocercosis. Five beagle dogs were injected subcutaneously with doramectin (400 microg/kg on 3 occasions 30 days apart q30d), while 5 other beagle dogs served as untreated controls. All dogs were inoculated with 40 infectious S. lupi larvae (L3) one month after the last doramectin treatment. All control dogs and 4/5 treated dogs became infected. Two control dogs died of ruptured aortic aneurysms, while no deaths occurred in treated dogs. Oesophageal nodules appeared 40-103 day later in treated as compared to control dogs, and eggs appeared in the faeces 49-106 day later in treated as compared to control dogs. The mean faecal egg count on day 223 in the treatment group was reduced by 99.77%. All control dogs had thoracic radiographic changes during the study, while only 2/5 study dogs showed radiographic changes. This study shows that although doramectin did not entirely prevent canine spirocercosis it reduced the clinical signs associated with infection and delayed and reduced egg output.

Somatic symptoms in social phobia: a treatment method based on rational emotive therapy and paradoxical interventions.

Social phobia is often accompanied by somatic symptoms such as trembling, blushing, and sweating. In cases where these symptoms are predominant and, rather than the social situation, represent the feared stimulus, their unpredictable occurrence may reduce the effectiveness of an otherwise successful treatment, such as exposure in vivo. In this study, a paradoxical treatment approach, combined with rational emotive therapy, is employed with three social phobic patients with fears of blushing, trembling, and sweating, respectively. Results indicate that a paradoxical treatment may be an effective strategy in reducing somatic symptoms in social phobia.

Clinical pharmacologic aspects of cefixime in dogs.

The minimal inhibitory concentration (MIC) of cefixime, a new third-generation orally administered caphalosporin, was determined for reference and clinical isolates from dogs. The MIC of the drug for all but 1 of the 18 Enterobacteriaceae isolates tested, 1 Pasteurella canis, 1 Rhodococcus equi, 1 Streptococcus canis, and 1 Streptococcus group G isolate, was less than 1.0 microgram/ml. The MIC for 9 Staphylococcus intermedius isolates ranged from 1.56 to 6.25 micrograms/ml and, for 8 Sta aureus isolates, the MIC values ranged from 1.56 to 12.5 micrograms/ml. Pseudomonas aeruginosa, Actinomyces sp, and a single Bordetella bronchiseptica isolate were considered resistant to cefixime. Cefixime was administered orally in 2 phases at a standard dosage of 5 mg/kg of body weight to clinically normal adult male and female dogs. In the first phase, the drug was given once as a capsule and once as a suspension. In the second phase, it was administered once per day for 6 consecutive days in capsule form. Serum drug concentration was determined by use of a microbiological assay, and the following kinetic values were estimated for each dog: area under the concentration-time curve, peak serum drug concentration (Cmax), time of Cmax, absorption half-life, and elimination half-life (t1/2el). The kinetic profile of the drug in serum after oral administration of a single dose of cefixime was similar, with mean Cmax values of 3.36 and 4.76 micrograms/ml after treatment with the capsule and suspension, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical manifestations of infectious canine cyclic thrombocytopenia.

This paper describes five naturally occurring clinical cases of infectious canine cyclic thrombocytopenia that were the first serologically confirmed cases of Ehrlichia platys infection in Israel. In the USA this disease is considered subclinical, but the dogs in this study developed distinct clinical abnormalities. The signs observed by the owners included anorexia, lethargy, depression, weight loss and a mucopurulent nasal discharge. The principal findings on physical examination included lymphadenomegaly, pale mucous membranes, fever and the presence of ticks. The main abnormal haematological and biochemical findings included thrombocytopenia, the presence of giant platelets, low haematocrit, monocytosis and low albumin concentrations. All five dogs were less than two years of age, and four were purebred dogs, suggesting that these two factors may be associated with increased risk to infection and clinical disease. Two of the dogs were seropositive to E canis, a finding which is compatible with other reports, and which confirms that combined infections of E platys and E canis are common; it also suggests that E canis infections may contribute to the pathogenesis of E platys. The distinct clinical manifestation of the disease in these five dogs suggests that there may be a different, more virulent strain of E platys in Israel.