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1. The aim of the study was to evaluate the pharmacokinetics (PKs) of tapentadol (TAP), a novel opioid analgesic, in laying hens after intravenous (IV) and oral (PO) administration and to quantify the concentrations of TAP residues in eggs. 2. Twenty healthy laying hens were divided into three groups: A (n = 6), B (n = 6) and C (n = 8). The study was conducted in two phases. Groups A and B received TAP by IV and PO routes at the dose of 1 and 5 mg/kg, respectively. 3. No visible adverse effects were observed after administration of the drug. TAP plasma concentrations were detectable up to 4 h following administration. Following IV administration, TAP plasma concentrations were only higher than the minimal effective concentration (148 ng/ml) reported for humans for 1 h. After single PO administration, plasma concentrations of TAP would not conform to software algorithms and the PK parameters were not calculated. TAP concentration following multiple PO doses at 5 mg/kg for 5 d was found to be higher and more persistent (12 h vs. 7 h) in yolk compared with albumen. 4. This is the first PK study on the novel atypical opioid TAP in laying hens. Further studies are required to investigate the analgesic efficacy and actual effective plasma concentration of TAP in this species. [ABSTRACT FROM AUTHOR]

Drugs that provide effective analgesia in cats are limited. The aim of the study was to assess the pharmacokinetics of grapiprant after 2 mg/kg administration via p.o. and i.v. routes in cats. Six healthy adult cats were used according to an open, single-dose, two-treatment, two-period, randomized cross-over design. Cats were assigned to two treatment groups and administered with 2 mg/kg of grapiprant (pure powder) through p.o. and i.v. administration. Blood samples were collected at preassigned times and analysed by a validated HPLC method. After both administrations, grapiprant concentrations were detectable in plasma for up to 24 hr in five of six animals. The critical parameters including clearance (173.2 ml hr−1 kg−1, range 120-326 ml hr−1 kg−1) and volume of distribution (918 ml/kg, range 611-1608 ml/kg) were calculated from the i.v. group. The mean oral F% was low (39.6% range 31.5%-45.2%). If the assumption that the minimal effective concentration in dogs (164 ng/ml) applies in cats too, grapiprant orally administered at 2 mg/kg might be effective for 10 hr. Further studies are necessary to establish the minimal effective concentration in this animal species. [ABSTRACT FROM AUTHOR]

Enrofloxacin belongs to the fluoroquinolone class of antibiotics. It is commonly used in a variety of reptile species due to its wide spectrum of efficacy, partly due to its formation of an active metabolite ciprofloxacin. Enrofloxacin shows wide disposition variability among all species resulting in large differences in the plasma concentrations of both enrofloxacin and ciprofloxacin. The aim of this study was to evaluate the pharmacokinetics of enrofloxacin and ciprofloxacin after a single intracoelomic injection of 10 mg/kg of enrofloxacin in 9 tortoises (Testudo hermanni). Blood samples were collected at 0, 0.5, 2, 4, 10, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 and 264 h and analyzed using a validated high performance liquid chromatography (HPLC) florescence method. Plasma concentrations of enrofloxacin were quantifiable in all subjects for up to 240 h, while ciprofloxacin was detected in all subjects up to 120 h. The Cmax (s) of enrofloxacin and ciprofloxacin were 8614 ± 1116 ηg/mL obtained at 2.19 h and 605 ± 43 ηg/mL obtained at 4.23 h, respectively. The values of Cmax/MIC ratio and AUC0-24/MIC ratio of enrofloxacin with a MIC value of 0.5 μg/mL were 17.23 and 132.78, respectively. In conclusion, an administration of 10 mg/kg of enrofloxacin via the intracoelomic route in Hermann's tortoises produced optimal pharmacodynamic parameters. [ABSTRACT FROM AUTHOR]

Treatments for inflammation and pain are important consideration in human and veterinary medicine. The classical drugs for treatments of inflammation and pain act by inhibition of cyclooxygenase and lypoxygenase pathways. However, there is still a need to develop new veterinary drugs and trials to apply human drugs to the veterinary field in order to increase the veterinary drug armamentarium. However, it is pivotal to experimentally test human drugs and therapies in veterinary species before veterinary clinical applications. The soluble epoxide hydrolase inhibitors (sEHIs), are novel active ingredients shown to have a number of beneficial effects. This has been especially demonstrated in many animal models in relation to inflammation and pain. The present review reports the state of the art of soluble epoxide hydrolase inhibitors and suggests their potential use in veterinary medicine. [ABSTRACT FROM AUTHOR]

The main aim of this study is to quantitatively evaluate the differences, in terms of exposure to PM (particulate matter), between WFO (working-from-office) and WFH (working-from-home) conditions. Two measurement surveys were performed: a long-term and a short-term campaign, focused on the monitoring of personal exposure to size-fractionated PM in these different working conditions. Results of the long-term campaign show that the WFH subject is exposed to higher (up to 4 times) PM concentration, compared to the WFO subject. Specific activities performed by the subjects impacted their exposure concentrations, even if the most relevant contribution to total exposure was made by desk work. Results of the short-term campaign indicate that the subjects can be divided into two groups: subjects most exposed during the WFH mode (HE_H - Higher_Exposure_Home) and subjects most exposed during the WFO mode (HE_O - Higher_Exposure_Office). HE_H group is exposed to levels of pollutants up to 4 times higher in the domestic than in the office environment, during the moment of desk work. The HE_O group is exposed to higher (double) concentration levels during desk work during the WFO day. Considering the possible growing trend towards remote work it is important to evaluate these "new domestic offices" comprehensively.

Background : Berberine is a natural alkaloid with hypoglycemic properties. However, its therapeutic use is limited by a very low oral bioavailability. Here we developed a new oral formulation of berberine based on Sucrosomial ® technology and tested its effect on insulin resistance. Methods : Sucrosomial ® berberine was first tested in vitro in the hepatoma cell line Huh7 to assess its effect on proteins involved in glucose homeostasis and insulin resistance. The pharmacokinetics and efficacy on insulin resistance were then studied in C57BL/6 mice fed with standard (SD) and high-fat diet (HFD) for 16 weeks and treated daily during the last 8 weeks with oral gavage of Sucrosomial ® berberine or berberine. Results : Sucrosomial ® berberine did not affect Huh7 cell viability at concentrations up to 40 µM. Incubation of Huh7 with 20 µM of Sucrosomial ® and control berberine induced glucokinase (GK) and the phosphorylation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), both known targets for the control of insulin resistance. In vivo, we observed an 8-fold higher plasma concentration after 3 weeks of oral administration of 50 mg/kg/day of Sucrosomial ® formulation compared to berberine. HFD, compared to SD, induced insulin resistance in mice as determined by oral glucose tolerance test (OGTT). The treatment with a 6.25 mg/kg/daily dose of Sucrosomial ® berberine significantly reduced the area under the curve (AUC) of OGTT (73,103 ± 8645 vs. 58,830 ± 5597 mg/dL × min), while control berberine produced the same effects at 50 mg/Kg/day (51518 ± 1984 mg/dL × min). Under these conditions, the two formulations resulted in similar berberine plasma concentration in mice. Nevertheless, a different tissue distribution of metabolites was observed with a significant accumulation of reduced, demethylated and glucuronide berberine in the brain after the oral administration of the Sucrosomial ® form. Glucuronide berberine plasma concentration was higher with Sucrosomial ® berberine compared to normal berberine. Finally, we observed similar increases of AMPK phosphorylation in the liver in response to the treatment with Sucrosomial ® berberine and berberine. Conclusions : The Sucrosomial ® formulation is an innovative and effective technology to improve berberine gastrointestinal (GI) absorption with proven in vitro and in vivo activity on insulin resistance.

Objective: To evaluate the pharmacokinetics of two doses of tramadol during isoflurane anaesthesia in sheep and their ability to prevent the cardiovascular response induced by surgical stimulation., Study Design: Prospective randomized controlled study., Animals: A total of 12 healthy sheep (mean weight, 47.5±7.9 kg) undergoing lumbar transpedicular intervertebral disk nucleotomy., Methods: Sheep were sedated with medetomidine, anaesthesia was induced with propofol and maintained with isoflurane at 1.5 vol.%. Baseline heart rate and blood pressure were measured and sheep were randomly assigned an intravenous injection of tramadol (4 or 6 mg kg -1 ). Fentanyl was injected as rescue analgesic if cardiovascular parameters were increased more than 20% compared to baseline. If those variables were below 20% of baseline, the concentration of isoflurane was gradually decreased until parameters returned to the original value. Blood collections were performed at pre-assigned times, and concentrations of tramadol and O-desmethyltramadol (M1) assessed by high-performance liquid chromatography., Results: Time from premedication to anaesthesia induction, anaesthesia time, propofol dose and intraoperative body temperature were similar between doses. Cardiovascular variables remained between ±20% of baseline value, and no statistical difference was observed between treatments. Regardless of the dose of tramadol administered, arterial blood pressure was statistically higher than baseline 10 minutes after tramadol administration, but it gradually returned to previous values. A two-compartment model and a non-compartment model described the pharmacokinetics of tramadol and M1, respectively. Plasma concentrations of tramadol rapidly decreased in the first 2 hours for both doses with an elimination half-life of more than 40 minutes. The M1 maximum concentration was similar for both doses, and it was detected in plasma after 35 minutes., Conclusions and Clinical Relevance: Both doses of tramadol provided adequate cardiovascular stability during spinal surgery in sheep. The pharmacokinetic variables may be used to plan the dosage regime during general anaesthesia., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

In the present study major polyphenols of pomegranate arils and peel by-products were extracted in 50% (v/v) aqueous ethanol, characterized and used in microbiological assays in order to test antimicrobial activity against clinically isolated human pathogenic microorganisms. Total concentration of polyphenols and in vitro antioxidant properties were determined by the Folin-Ciocalteu and DPPH methods, respectively. The most abundant bioactive molecules, including anthocyanins, catechins, tannins, gallic and ellagic acids were identified by RP-HPLC-DAD, also coupled to off-line matrix assisted laser desorption/ionization (MALDI-TOF) mass spectrometry (MS). The inhibitory spectrum of extracts against test microorganisms was assessed by the agar well-diffusion method. Data herein indicated that both pomegranate aril and peel extracts have an effective antimicrobial activity, as evidenced by the inhibitory effect on the bacterial growth of two important human pathogens, including Staphylococcus aureus and Escherichia coli, which are often involved in foodborne illness., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Flupirtine (FLU) is a non-opioid analgesic with no antipyretic or anti-inflammatory effects which is used in the treatment of pain in humans. There is a substantial body of evidence on the efficacy of FLU in humans but this is inadequate for the recommendation of its off-label use in veterinary clinical practice. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after intravenous (IV), oral immediate release (POIR), oral prolonged release (POPR) and rectal (RC) administrations in healthy dogs., Study Design: Four-treatment, single-dose, four-phase, unpaired, cross-over design (4×4 Latin-square)., Animals: Six adult Labrador dogs., Methods: Animals in groups 1, 2 and 4 received a single dose of 5 mg kg(-1) FLU administered by IV, POIR and RC routes. Group 3 received a single dose of 200 mg subject(-1) via the POPR route. The wash-out periods were 1 week. Blood samples (1 mL) were collected at assigned times for 48 hours and plasma FLU concentrations were analysed by a validated HPLC method., Results: Adverse effects including salivation, tremors and vomiting were noted in the IV group and resolved spontaneously within 10 minutes. These effects did not occur in the other groups. The FLU plasma concentrations were detectable in all of the treatment groups for 36 hours following administration. The pharmacokinetic profiles after extravascular administrations showed similar trends. The bioavailability values after POIR, POPR and RC were 41.93%, 36.78% and 29.43%, respectively. There were no significant differences in pharmacokinetic profiles between the POIR and POPR formulations. A 5 mg kg(-1) POIR dose or a 200 mg subject(-1) POPR dose gave plasma concentrations similar to those reported in humans after clinical dosing., Conclusion and Clinical Relevance: This study provides pharmacokinetic data that can be used to design further studies to investigate FLU in dogs., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Combination therapy with two or more analgesics is widely used for conditions associated with moderate to severe pain. Combinations of diverse analgesics with different modes of action can improve the risk-benefit ratio of analgesic treatments. The aim of this study is to evaluate the antinociceptive effect of tapentadol (TAP) and flupirtine (FLP), when administered separately or in combination, as well as their synergistic interaction in the orofacial formalin test in rats. After i.p. injection of TAP at different doses (2, 5, 10 and 15mg/kg), the biphasic nociceptive behavior was reduced in a dose-dependent manner in both phase I and II. Conversely, i.p. injection of FLP at different doses (0.6, 1.6, 3.3, 6.6, 16.6 and 22.2mg/kg) induced a dose-dependent antinociceptive effect in phase II only. TAP was found to be more effective than FLP. The interaction between TAP and FLP was synergistic in phase II with an interaction index (γ) of 0.50±0.24. The data reported in this study indicate that FLP enhances the antinociceptive effect of TAP and this drug combination might be potentially useful in the treatment of chronic pain., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In this work, we characterized conjugated linolenic acids (e.g., punicic acid) as the major components of the hydrophilic fraction (80% aqueous methanol extract) from pomegranate (Punica granatum L.) seed oil (PSO) and evaluated their anti-inflammatory potential on some human colon (HT29 and HCT116), liver (HepG2 and Huh7), breast (MCF-7 and MDA-MB-231) and prostate (DU145) cancer lines. Our results demonstrated that punicic acid and its congeners induce a significant decrease of cell viability for two breast cell lines with a related increase of the cell cycle G0/G1 phase respect to untreated cells. Moreover, the evaluation of a great panel of cytokines expressed by MCF-7 and MDA-MB-231 cells showed that the levels of VEGF and nine pro-inflammatory cytokines (IL-2, IL-6, IL-12, IL-17, IP-10, MIP-1α, MIP-1β, MCP-1 and TNF-α) decreased in a dose dependent way with increasing amounts of the hydrophilic extracts of PSO, supporting the evidence of an anti-inflammatory effect. Taken together, the data herein suggest a potential synergistic cytotoxic, anti-inflammatory and anti-oxidant role of the polar compounds from PSO.