[Show abstract][Hide abstract] ABSTRACT: Cell-penetrating peptides (CPPs) are a group of peptides, which have the ability to cross cell membrane bilayers. CPPs themselves can exert biological activity and can be formed endogenously. Fragmentary studies demonstrate their ability to enhance transport of different cargoes across the blood-brain barrier (BBB). However, comparative, quantitative data on the BBB permeability of different CPPs are currently lacking. Therefore, the in vivo BBB transport characteristics of five chemically diverse CPPs, i.e. pVEC, SynB3, Tat 47–57, transportan 10 (TP10) and TP10-2, were determined. The results of the multiple time regression (MTR) analysis revealed that CPPs show divergent BBB influx properties: Tat 47–57, SynB3, and especially pVEC showed very high unidirectional influx rates of 4.73 μl/ (g × min), 5.63 μl/(g × min) and 6.02 μl/(g × min), respectively, while the transportan analogs showed a negligible to low brain influx. Using capillary depletion, it was found that 80% of the influxed peptides effectively reached the brain parenchyma. Except for pVEC, all pep-tides showed a significant efflux out of the brain. Co-injection of pVEC with radioiodinated bovine serum albumin (BSA) did not enhance the brain influx of radiodionated BSA, indicating that pVEC does not itself significantly alter the BBB properties. A saturable mechanism could not be demonstrated by co-injecting an excess dose of non-radiolabeled CPP. No significant regional differences in brain influx were observed, with the exception for pVEC, for which the regional variations were only marginal. The observed BBB influx transport properties cannot be correlated with their cell-penetrating ability, and therefore, good CPP properties do not imply efficient brain influx.
PLoS ONE 10/2015; 10(10):e0139652. DOI:10.1371/journal.pone.0139652 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT In this study, female canines referred with clinical signs consistent with pyometra were prospectively evaluated. Signalment, clinical signs, laboratory findings and surgical findings were compared between dogs with and without bacterial isolation based on aerobic techniques. Patients with positive bacterial isolation were placed in the pyometra group, whereas patients with negative bacterial isolation were grouped as mucometra. A total of 140 dogs (118 with pyometra and 22 with mucometra) met the inclusion criteria. Prereferral antibiotic administration was associated with a prolonged duration of clinical signs in the patients of the pyometra group (12 ± 2 days versus 7 ± 1 days; P=0.006). In the pyo-metra patients, clinical signs, like pyrexia, anorexia and discomfort on abdominal palpation, were observed more commonly than in the mucometra group. The total leukocyte count was the only parameter that differed significantly between the two groups (P=0.01). Although no difference in color and consistency of the uterine fluid was noted, the uteri of the pyometra group were heavier (851.80 ± 800.30 g compared to 263.50 ± 297.10 g). E. coli was the most commonly isolated bacterium (92/123). SAMENVATTING In deze studie werden vrouwelijke honden met klinische klachten verenigbaar met pyometra prospectief geëvalueerd. Het signalement, de klinische symptomen, laboratoriumresultaten en chirur-gische bevindingen werden vergeleken tussen honden met en zonder bacteriële isolatie op basis van aërobe technieken. Patiënten met een positieve bacteriële isolatie werden in de pyometragroep ge-klasseerd, terwijl patiënten met een negatieve bacteriële isolatie als honden met mucometra werden gegroepeerd. Honderdveertig honden (118 met pyometra en 22 met mucometra) voldeden aan de in-clusiecriteria. De toediening van een antibioticum vooraleer door te verwijzen was geassocieerd met verlengde klinische symptomen bij de patiënten van de pyometragroep (12 ± 2 dagen versus 7 ± 1 dagen; P = 0,006). Bij de pyometrapatiënten werden klinische symptomen, zoals koorts, anorexia en ongemak bij abdominale palpatie vaker waargenomen dan bij de mucometrapatiënten. Het totale aantal leukocyten was de enige parameter die significant verschilde (P=0,01). Hoewel er tussen de twee groepen geen verschil in kleur en consistentie van de baarmoedervloeistof werd opgemerkt, was de baarmoeder van de honden met pyometra zwaarder dan bij de honden met mucometra (851,80 ± 800,30 g versus 263,50 ± 297,10 g). E. coli was de vaakst geïsoleerde bacterie (92/123).
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the effect of epinephrine-enhanced computed tomographic arthrography (CTA) on the image sharpness of the lateral and medial glenohumeral ligaments (LGHL and MGHL, respectively), biceps tendon (BT) and joint cartilage (JC) in the canine shoulder.The shoulders of eight normal dogs were examined using a 4-slice helical CT scanner. The right shoulders were injected with Iohexol and the left shoulders with a mixture of Iohexol and epinephrine. CTA images were obtained after 1, 3, 5, 9, 13, 20 and 30. min and the image sharpness of the intra-articular structures in both shoulders was graded for visibility. The attenuation values were measured to examine the persistence of contrast appearance. Admixture of epinephrine and Iohexol significantly improved the image sharpness of the LGHL and the BT, especially on delayed CTA images. The use of epinephrine did not negatively affect post-CTA recovery.
[Show abstract][Hide abstract] ABSTRACT: Ketamine, a dissociative anesthetic frequently used in veterinary medicine, possesses rapid-acting antidepressant effects in humans possibly indicating an interaction with the cerebral perfusion or with the serotonergic system. In this single-photon emission computed tomography study, 7 healthy dogs were used to investigate the influence of ketamine on the regional cerebral blood flow using technetium-99m-ethyl cysteinate dimer and on the binding of the 5-hydroxytryptamine 2A receptor radioligand iodine-123 labeled R91150 in the canine brain. Ketamine increased the regional perfusion in the left frontal cortex and right parietal cortex. Significant changes in the distribution of iodine-123 labeled R91150 were not observed. This study demonstrated an acute effect of ketamine on the regional brain perfusion but not on the 5-hydroxytryptamine 2A receptors in the canine brain in the dose used in this study.
Journal of Veterinary Behavior Clinical Applications and Research 04/2015; 10(4). DOI:10.1016/j.jveb.2015.03.009 · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prepubertal gonadectomy (PPG) is promoted as a way of managing overpopulation in cats, but concerns about PPG and potential health issues still exist. The objective of the present study was to evaluate short-term and long-term health problems in cats subjected to PPG in comparison to gonadectomy at traditional age (TAG). In a prospective clinical trial, 800 shelter kittens aged between approximately 8 weeks and 12 weeks were recruited before adoption and randomly assigned to either the PPG group (gonadectomy performed immediately) or the TAG group (gonadectomy delayed until six months to eight months of age). Short-term health issues included mortality between when kittens arrived at the clinic and up to seven days after they returned to the shelter, as well as the occurrence of various other health issues arising in the first month following adoption. Kittens were followed-up until 24 months of age specifically for feline lower urinary tract disease, urethral obstruction (male cats), lameness, fractures and hypersensitivity disorders with dermatological presentation. In the short term, there were no significant differences between health problems in PPG and TAG kittens. Similarly, no significant differences were observed between treatment groups in terms of the type or number of health issues in the long term. In conclusion, there are no health-related contraindications to advocating PPG strategies in shelter cats. Ideally, PPG should be performed at the shelter facility itself as long as excellent infectious disease control and postoperative clinical observation before adoption are guaranteed.
British Veterinary Association.
[Show abstract][Hide abstract] ABSTRACT: In this study, female canines referred with clinical signs consistent with pyometra were prospectively evaluated. Signalment, clinical signs, laboratory findings and surgical findings were compared between dogs with and without bacterial isolation based on aerobic techniques. Patients with positive bacterial isolation were placed in the pyometra group, whereas patients with negative bacterial isolation were grouped as mucometra. A total of 140 dogs (118 with pyometra and 22 with mucometra) met the inclusion criteria. Prereferral antibiotic administration was associated with a prolonged duration of clinical signs in the patients of the pyometra group (12 ± 2 days versus 7 ± 1 days; P=0.006). In the pyometra patients, clinical signs, like pyrexia, anorexia and discomfort on abdominal palpation, were observed more commonly than in the mucometra group. The total leukocyte count was the only parameter that differed significantly between the two groups (P=0.01). Although no difference in color and consistency of the uterine fluid was noted, the uteri of the pyometra group were heavier (851.80 ± 800.30 g compared to 263.50 ± 297.10 g). E. coli was the most commonly isolated bacterium (92/123).
[Show abstract][Hide abstract] ABSTRACT: A young Labrador Retriever was presented for treatment of severe distal hindlimb necrosis caused by bandage ischemia. During digit amputation at the metatarsophalangeal joints, the third and fourth digital pads were salvaged and transferred to the metatarsal stump to create a weight-bearing surface. Negative pressure wound therapy (NPWT) was utilized for flap immobilization and to promote granulation tissue in the remaining wound defect. Sturdy adherence of the digital pads was achieved after only four days. The skin defect healed completely by second intention and the stump was epithelialized with a thin pad after three months. At the nine month follow-up examination, the stump had a thick hyperkeratinized pad. The dog walked and ran without any apparent signs of discomfort and compensated for the loss of limb length by extending the stifle and tarsocrural joints. Despite a challenging wound in a difficult anatomical location, digital pad flap transfer and NPWT proved successful in restoring long-term ambulation in an active large breed dog.
Veterinary and Comparative Orthopaedics and Traumatology 12/2014; 28(1). DOI:10.3415/VCOT-14-04-0056 · 0.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Cavalier King Charles Spaniels (CKCS) have a high prevalence of Chiari-like malformation (CM). Herniation of the cerebellum into the foramen magnum is a key diagnostic feature for CM. Midsagittal MR images are the preferred technique for visualizing cerebellar herniation (CH).Objective
To investigate whether CT can be used to diagnose CH.AnimalsFifteen client-owned CKCS dogs referred for investigation of the brain and cranial cervical spine on MRI and CT.Methods
Two reviewers retrospectively analyzed midsagittal T1WSE and T2WSE MR images and midsagittal pre- and postcontrast 2D multiplanar reformatted CT images from each dog for the presence of CH. And, if present, the length (mm, CHL) of the herniation was measured. The results were analyzed statistically.ResultsThere was no significant difference between the different observers and techniques for the detection of CH and measurement of CHL. Overall, the CHL was longer on the CT images.Conclusion and Clinical ImportanceBoth techniques are useful for detecting CH and measuring CHL. Because CHL does not have a known direct impact on the clinical presentation of CM, CT can be used as a diagnostic tool in a routine clinical practice for CM in CKCS when MRI is not available. We emphasize that MRI is the standard screening technique in CKCS for breeding purposes to detect the presence of CM and SM and, at the current time, CT cannot replace MRI.
Journal of Veterinary Internal Medicine 11/2014; 29(1). DOI:10.1111/jvim.12498 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Enkephalins are active in regulation of nociception in the body and are key in development of new synthetic peptide analogs that target centrally located opioid receptors. In this study, we investigated the in vivo blood–brain barrier (BBB) penetration behavior and antinociceptive activity of two cyclic enkephalin analogs with a thiourea (CycS) or a N-methyl-guanidine bridge (CycNMe), and their linear counterparts (LinS and LinNMe) in mice, as well as their in vitro metabolic stability. 125I-LinS had the highest blood–brain clearance (K1 = 3.46 μL/g min), followed by 125I-LinNMe, 125I-CycNMe, and 125I-CycS (K1 = 1.64, 0.31, and 0.11 μL/g min, respectively). Also, these peptides had a high metabolic stability (t1/2 > 1 h) in mouse serum and brain homogenate, and half-inhibition constant (Ki) values in the nanomolar range with predominantly μ-opioid receptor selectivity. The positively charged NMe-enkephalins showed a higher antinociceptive activity (LinNMe: 298% and CycNMe: 205%), expressed as molar-dose normalized area under the curve (AUC) relative to morphine, than the neutral S-enkephalins (CycS: 122% and LinS: 130%).
[Show abstract][Hide abstract] ABSTRACT: Contrast-enhanced ultrasonography of the left kidney was performed using a commercial contrast agent in six healthy adult purpose-bred cats. A cross-over design was used to compare three protocols: (1) awake, (2) butorphanol (0.4 mg/kg IM), and (3) propofol (3.5-7.7 mg/kg IV boluses to effect). Time-intensity curves were created from two regions-of-interest drawn in the renal cortex. The curves were analyzed for blood flow parameters representing blood volume (base intensity, peak intensity, area-under-curve) and blood velocity (arrival time, time-to-peak, wash-in/out). There was no difference in the subjective enhancement pattern between the three protocols. No significant effect of butorphanol was observed in any of the perfusion parameters (P > 0.05). Propofol did not influence the most important perfusion parameter, area-under-the-curve, and is adequate for use in contrast-enhanced ultrasound studies.
The Veterinary Journal 10/2014; 202(3). DOI:10.1016/j.tvjl.2014.10.008 · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To gain insights into the working mechanism of morphine, regional cerebral blood flow (rCBF) patterns after morphine administration were assessed in dogs. In a randomized cross-over experimental study, rCBF was estimated with 99mTc-Ethylcysteinate Dimer single photon emission computed tomography in 8 dogs at baseline, at 30 minutes and at 120 minutes after a single bolus of morphine. Perfusion indices (PI) in the frontal, parietal, temporal and occipital cortex and in the subcortical and cerebellar region were calculated. PI was significantly decreased 30 min after morphine compared to baseline in the right frontal cortex. The left parietal cortex and subcortical region showed a significantly increased PI 30 min after morphine compared to baseline. No significant differences were noted for the other regions or at other time points. In conclusion, a single bolus of morphine generated a changing rCBF pattern at different time points.
PLoS ONE 10/2014; 9(10):e109680. DOI:10.1371/journal.pone.0109680 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prepubertal gonadectomy (PPG) is promoted for population control in cats, but concerns related to health and behavior still exist. From a behavioral point of view, in order for PPG to be an acceptable alternative for traditional age gonadectomy (TAG), the occurrence of undesirable behavior should be unaffected by age at gonadectomy. The aims of this study were to investigate (1) whether the average number of (potentially) undesirable behaviors in shelter kittens during 24 months after adoption was associated with the age at gonadectomy, and (2) whether social or environmental factors were related to the occurrence of commonly reported undesirable behaviors (inappropriate elimination, fearfulness, aggression and destruction).
Eight hundred healthy kittens between the estimated age of 8 to 12 weeks (0.7 and 1.4 kg) were recruited from animal shelters in Flanders, Belgium. Before adoption, kittens were randomly assigned to a PPG (gonadectomy upon assignment) and TAG group (gonadectomy between 6 to 8 months of age). Online short- and long-term follow-up were conducted using a 30-day diary immediately after adoption and surveys at 2, 6, 12, 18 and 24 months after adoption.
Mean number of potentially undesirable behaviors per day during the first month after adoption was not significantly different between PPG (1.48 ± 0.957) and TAG (1.39 ± 0.899) kittens (P = 0.32), and neither was the evolution of the mean number of potentially undesirable behaviors and undesirable behaviors during the long-term follow-up (P = 0.0946 and P = 0.10 respectively). The occurrence of inappropriate elimination, fearful behavior, non-play related aggression and destruction was associated with other social and environmental variables (e.g. the use of punishment by the owner and friendliness toward a stranger).
In conclusion, this study in shelter cats did not demonstrate an effect of age at time of gonadectomy on the mean number of (potentially) undesirable behaviors during 24 months after adoption. Other factors seem to play a more dominating role in the development of such behaviors.
Journal of Veterinary Behavior Clinical Applications and Research 09/2014; 9(5). DOI:10.1016/j.jveb.2014.05.003 · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1-month washout), a combination of dexmedetomidine (40 μg/kg) and buprenorphine (20 μg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24-h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography–tandem mass spectrometry. Plasma concentration–time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration–time curve (AUC) and the maximum plasma concentrations (Cmax) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach Cmax was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40 μg/kg) combined with buprenorphine (20 μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site.
Journal of Veterinary Pharmacology and Therapeutics 09/2014; 38(2). DOI:10.1111/jvp.12172 · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anaesthetic and analgesic effects of three different injectable anaesthetic combinations for prepubertal gonadectomy (PPG) in cats were studied. One anaesthetic protocol was compared with a similar one for gonadectomy at traditional age (TAG). Kittens were randomly assigned to PPG or TAG. For PPG, three different protocols were compared: (1) intramuscular (IM) administration of 60 μg/kg dexmedetomidine plus 20 μg/kg buprenorphine followed by an IM injection of the anaesthetic agent (20 mg/kg ketamine) (DB-IM protocol); (2) oral transmucosal (OTM) administration of 80 μg/kg dexmedetomidine plus 20 μg/kg buprenorphine followed by an IM injection of 20 mg/kg ketamine combined with 20 µg/kg dexmedetomidine (DB-OTM protocol); (3) IM injection of a 40 μg/kg medetomidine-20 μg/kg buprenorphine-20 mg/kg ketamine combination (MBK-IM protocol). For TAG, a DB-IM protocol was used, but with different doses for dexmedetomidine (40 μg/kg) and ketamine (5 mg/kg). All cats (PPG and TAG) received a non-steroidal anti-inflammatory before surgery. Anaesthetic and analgesic effects were assessed pre- and postoperatively (until 6 h). Cumulative logit, linear and logistic regression models were used for statistical analysis. Compared with the DB-OTM protocol, the DB-IM and MBK-IM protocols provided better anaesthesia with fewer adverse effects in PPG cats. Postoperative pain was not significantly different between anaesthetic protocols. PPG and TAG cats anaesthetised with the two DB-IM protocols differed significantly only for sedation and pain scores, but sedation and pain scores were generally low. Although there were no anaesthesia-related mortalities in the present study and all anaesthetic protocols for PPG in cats provided a surgical plane of anaesthesia and analgesia up to 6 h postoperatively, our findings were in favour of the intramuscular (DB-IM and MBK-IM) protocols.
Journal of Feline Medicine & Surgery 08/2014; 17(6). DOI:10.1177/1098612X14546919 · 1.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Septic peritonitis occurs relatively commonly in dogs. Secondary septic peritonitis is usually associated with perforation of intestines or infected viscera, such as the uterus in pyometra cases. The aim of this study was to evaluate the bacterial flora in the ovarian bursae of intact bitches as a potential source of contamination. One hundred forty dogs, clinically suspected of pyometra, were prospectively enrolled. The control group consisted of 26 dogs that underwent elective ovariohysterectomies and 18 dogs with mammary gland tumors that were neutered at the time of mastectomy. Bacteriology samples were taken aseptically at the time of surgery from the bursae and the uterus in all dogs. Twenty-two dogs that were clinically suspected of pyometra had sterile uterine content ("mucometra" cases); the remaining 118 had positive uterine cultures ("pyometra" cases) and septic peritoneal fluid was present in 10% of these cases. Of the 118 pyometra cases, 9 had unilateral and 15 had bilateral bacterial colonization of their ovarian bursae. However, the bacteria from the ovarian bursa were similar to those recovered from the uterine pus in only half of the cases. Furthermore, positive bursae were also seen in one mucometra dog (unilateral) and in four control dogs (two unilateral and two bilateral). The data illustrate that the canine ovarian bursa can harbor bacteria. The biological importance of these isolations remains unclear.
[Show abstract][Hide abstract] ABSTRACT: Down-stream neuronal alterations, including changes in the 5-HT-2A receptor system, play an important role in the etiology and treatment of depression. The present study examined the effect of prolonged opioid treatment on cerebral 5-HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine treatment (oral sustained release morphine 20 mg twice daily for ten days) with 123I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor binding indices (BI) for the frontal, parietal, temporal and occipital cortex and the subcortical region were calculated. Statistical analysis was performed using a linear mixed-effect model with treatment as fixed effect and dog as random effect. Morphine treatment significantly (p≤0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A receptor availability following prolonged morphine exposure provides further evidence for an interaction between the opioid and serotonergic system.
European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2014; 24(7). DOI:10.1016/j.euroneuro.2014.03.004 · 4.37 Impact Factor