Comparison between continuous rate infusion and target-controlled infusion of propofol in dogs: a randomized clinical trial.

OBJECTIVE: To compare a propofol continuous rate infusion (CRI) with a target-controlled infusion (TCI) in dogs. STUDY DESIGN: Randomized prospective double-blinded clinical study. ANIMALS: A total of 38 healthy client-owned dogs. METHODS: Dogs premedicated intramuscularly with acepromazine (0.03 mg kg-1) and an opioid (pethidine 3 mg kg-1, morphine 0.2 mg kg-1 or methadone 0.2 mg kg-1) were allocated to P-CRI group (propofol 4 mg kg-1 intravenously followed by CRI at 0.2 mg kg-1 minute-1), or P-TCI group [propofol predicted plasma concentration (Cp) of 3.5 µg mL-1 for induction and maintenance of anaesthesia via TCI]. Plane of anaesthesia, heart rate, respiratory rate, invasive blood pressure, oxygen haemoglobin saturation, end-tidal carbon dioxide and body temperature were monitored by an anaesthetist blinded to the group. Numerical data were analysed by unpaired t test or Mann-Whitney U test, one-way analysis of variance and Dunnett's post hoc test. Categorical data were analysed with Fisher's exact test. Significance was set for p < 0.005. RESULTS: Overall, propofol induced a significant incidence of relative hypotension (mean arterial pressure 20% below baseline, 45%), apnoea (71%) and haemoglobin desaturation (65%) at induction of anaesthesia, with a higher incidence of hypotension and apnoea in the P-CRI than P-TCI group (68% versus 21%, p = 0.008; 84% versus 58%, p = 0.0151, respectively). Propofol Cp was significantly higher at intubation in the P-CRI than P-TCI group (4.83 versus 3.5 µg mL-1, p < 0.0001), but decreased during infusion, while Cp remained steady in the P-TCI group. Total propofol administered was similar between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Both techniques provided a smooth induction of anaesthesia but caused a high incidence of side effects. Titration of anaesthesia with TCI caused fewer fluctuations in Cp and lower risk of hypotension compared with CRI.

Pharmacokinetics of acetaminophen after intravenous and oral administration in fasted and fed Labrador Retriever dogs.

Acetaminophen (paracetamol) is used in dogs to manage fever and mild pain. The aim of this study was to assess the pharmacokinetics of acetaminophen in both fed and fasted Labrador Retrievers after a single intravenous and oral administration (20 mg/kg). Six healthy dogs underwent three treatments in a randomized block study (a, n = 2; b, n = 2; c, n = 2). In phase one, group a received acetaminophen intravenously, group b and c orally after being fasted and fed, respectively. In phase two and three, groups were swapped, and the experiment was repeated. At the end of the trial, each dog received the same treatment. Acetaminophen plasma concentrations were detected using a validated HPLC-UV method. The pharmacokinetic analysis was performed using a noncompartmental model. Clearance, volume at steady state and half-life of acetaminophen in Labrador Retrievers were 0.42 L/kg hr, 0.87 L/kg and 1.35 hr, respectively. No significant statistical differences were found between fasted and fed dogs regarding maximum plasma concentration, time at maximum concentration and bioavailability as measured by the AUC. Feeding does not significantly affect the acetaminophen oral pharmacokinetics.

Expression of functional TRPV1 receptor in primary culture of canine keratinocytes.

The interest for the endovanilloid system and for transient receptor potential vanilloid 1 (TRPV1) is continuously increasing, due to their involvement in inflammation, nociception and pruritus. Even if TRPV1 enrolment was highlighted in both physiological and pathological conditions, some aspects remain unclear, mostly in veterinary medicine. This study aimed to verify the expression and functionality of TRPV1 in canine keratinocytes to investigate in vitro the role of TRPV1 in these cells that are involved in different cutaneous pathologies. Keratinocytes primary cultures were isolated from bioptical samples and cultivated. Binding assay (using 3 [H]-resiniferatoxin), displacement assay (in the presence of 1.2 nM 3 [H]-resiniferatoxin) and functional assays (in the presence of 1 µCi/45 Ca2+ ) with vanilloid agonists and antagonists, specifically addressed to TRPV1 receptor, were performed. Binding assay demonstrated the presence of measurable concentrations of TRPV1 (Bmax  = 1,240 ± 120 fmol/mg protein; Kd  = 0.01 ± 0.004 nM). Displacement assay highlighted the highest affinity for resiniferatoxin (RTX) and 5-iodo-resiniferatoxin (5-I-RTX), among agonists and antagonists, respectively. The same compounds results as the most potent in the functional assays. This study demonstrated the identification and the characterization of TRPV1 receptor in primary canine keratinocytes cultures. The results are promising for a clinical use, but further in vivo investigations are required.

Data on European non-residential buildings.

This data article relates to the research paper Energy consumption and efficiency technology measures in European non-residential buildings (D'Agostino et al., 2017) [1]. The reported data have been collected in the framework of the Green Building Programme that ran from 2006 to 2014. The project has encouraged the adoption of efficiency measures to boost energy savings in European non-residential buildings. Data focus on the one-thousand buildings that joined the Programme allowing to save around 985 GWh/year. The main requirement to join the Programme was the reduction of at least 25% primary energy consumption in a new or retrofitted building. Energy consumption before and after the renovation are provided for retrofitted buildings while, in new constructions, a building had to be designed using at least 25% less energy than requested by the country's building codes. The following data are linked within this article: energy consumption, absolute and relative savings related to primary energy, saving percentages, implemented efficiency measures and renewables. Further information is given about each building in relation to geometry, envelope, materials, lighting and systems.

Transient receptor potential vanilloid 1 expression and functionality in mcf-7 cells: a preliminary investigation.

PURPOSE: Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel belonging to the transient receptor potential family, and it is expressed in different neoplastic tissues. Its activation is associated with regulation of cancer growth and progression. The aim of this research was to study the expression and pharmacological characteristics of TRPV1 in cells derived from human breast cancer MCF-7 cells. METHODS: TRPV1 presence was assessed by binding studies and Western blotting. Receptor binding characteristics were evaluated through competition assays, while 3-(4,5-dimethylthiazol-2-yl)-2,5,-dipheyltetrazolium bromide reduction assays were performed to confirm an early hypothesis regarding the modulation of cancer cell proliferation. The functionality of TRPV1 was evaluated by measuring Ca(2+) uptake in the presence of increasing concentrations of TRPV1 agonists and antagonists. RESULTS: Binding studies identified a single class of TRPV1 (Bmax 1,492±192 fmol/mg protein), and Western blot showed a signal at 100 kDa corresponding to the molecular weight of human TRPV1. Among the different tested agonists and antagonists, anandamide (Ki: 2.8×10(-11) M) and 5-iodoresiniferatoxin (5-I-RTX) (Ki: 5.6×10(-11) M) showed the highest degrees of affinity for TRPV1, respectively. All tested TRPV1 agonists and antagonists caused a significant (p<0.05) decrease in cell growth rate in MCF-7 cells. For agonists and antagonists, the efficacy of tested compounds displayed the following rank order: resiniferatoxin>anandamide>capsaicin and 5-I-RTX=capsazepine, respectively. CONCLUSION: These data indicate that both TRPV1 agonists and antagonists induce significant inhibition of MCF-7 cell growth. Even though the mechanisms involved in the antiproliferative effects of TRPV1 agonists and antagonists should be further investigated, it has been suggested that agonists cause desensitization of the receptor, leading to alteration in Ca(2+)-influx regulation. By contrast, antagonists cause a functional block of the receptor with consequent fatal dysregulation of cell homeostasis.

Oral administration of tepoxalin in the horse: a PK/PD study.

Tepoxalin is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory, and antipyretic properties and has been recently introduced into veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profile of tepoxalin to assess whether it would be suitable for clinical use in horses. Six female fasting/fed horses were given 10mg/kg tepoxalin orally in a cross-over study. After administration, tepoxalin underwent rapid and extensive hydrolytic conversion to its carboxylic acid metabolite RWJ-20142. In animals that had been fed, the plasma concentrations of tepoxalin were undetectable, whereas in fasting animals they were close to the limit of quantification of the method. No differences between the fasting/fed groups in RWJ-20142 plasma concentrations were shown. Tepoxalin showed a strong and long-lasting ex vivo inhibitory activity against cyclooxygenase (COX)-1, mainly due to its main metabolite RWJ-20142. Tepoxalin and RWJ-20142 do not seem to possess either COX-2 or 5-lipoxygenase inhibitory activity in the horse. These features suggest that the drug is a selective COX-1 inhibitor in horses, with no significant anti-inflammatory activity. Thus, its long term use in equine practice could be of concern.

Effects of housing and short-term transportation on hormone and lymphocyte receptor concentrations in beef cattle.

The experiment was designed to evaluate the effects of housing system and short-term transportation on the pituitary and adrenal response and on blood progesterone concentrations of beef cattle. Since the use of steroid hormones in farm animals has been banned in the EU (Council Directive 96/22/EC), it seems important to study the possible modifications in serum progesterone concentrations induced by stress in cattle. Thirty-two, 6 months old male Piedmontese beef cattle (16 reared in a littered loose house, Group A, and 16 housed in a littered tying stall barn, Group B) were blood sampled at T1 (6 months old), T2 (12 months old), T3 (18 months old, before transportation to the slaughterhouse) and T4 (after transportation to the slaughterhouse) in order to measure hormonal concentrations and lymphocyte glucocorticoid (GR) and ß-adrenergic (ß-AR) receptor concentrations. Circulating hormone concentrations were measured using commercial radioimmunoassay kits, whereas lymphocyte receptor density was determined through binding assays. In beef cattle housed in tie stall barn a significant increase in serum cortisol concentration was observed at T3, whereas there was no effect of the housing system on blood progesterone concentrations. Short-term transportation caused a significant increase in blood cortisol and catecholamine concentrations in both groups, whereas lymphocyte GR and ß-AR significantly decreased in Group A. Our data confirm the activation of the hypothalamic-pituitary-adrenal axis and the catecholaminergic system in short-term transportation and suggest that the stress-induced increase in circulating progesterone concentrations does not exceed the limit established by pending legislation.

Regulation of tissue beta-adrenergic, glucocorticoid and androgen receptors induced by repeated exposure to growth promoters in male veal calves.

Biochemical modifications induced by a combination of anabolic compounds in target organs of male veal calves have been evaluated. Six male Friesian crossbred calves were treated with of 17beta-estradiol, dexamethasone sodium phosphate and clenbuterol or served as controls. beta-Adrenoceptors (beta-ARs) were measured in myocardium, lung, spleen, cerebral cortex, hippocampus, thalamus, hypothalamus, and hypophysis, glucocorticoid receptors (GRs) in the spleen and androgen receptors (AnRs) in the testis, by binding assay. A significant decrease in beta-ARs was observed in all tissue samples from treated animals. In the spleen the two GR subtypes found, low (LA) and high (HA) affinity GRs, were down-regulated by the treatment. A significant (P<0.05) decrease of testis weight and a significant (P<0.05) up-regulation of AnRs was also observed. Our data demonstrate that long-term treatment with anabolic compounds markedly affects receptor concentrations in target organs of male veal calves. Thus, studies investigating biological assays as screening methods to detect such compounds should be encouraged.