Pharmacokinetic/pharmacodynamic assessments of 10 mg/kg tramadol intramuscular injection in yellow‐bellied slider turtles (Trachemys scripta scripta)

In reptiles, administration of opioid drugs has yielded unexpected results with respect to analgesia. The aims of this study were to assess the pharmacokinetic/pharmacodynamic (PK/PD) properties of tramadol and its active metabolite M1 and to evaluate the effect of the renal portal system on the PK/PD parameters in yellow‐bellied slider turtles. Turtles (n = 19) were randomly assigned to four treatment groups, according to a masked, single‐dose, four‐treatment, unpaired, four‐period crossover design. Group A (n = 5) received a single i.m. dose of tramadol (50 mg/mL) at 10 mg/kg in the proximal hindlimb. Group B (n = 5) received the same i.m. dose but in the forelimb. Groups C (n = 5) and D (n = 4) received a single i.m. injection of saline (NaCl 0.9%) of equivalent volume to the volumes of tramadol injected in the hind‐ and forelimb, respectively. Groups were rotated (1‐month washout period) until the completion of the crossover study. Tramadol plasma concentrations were evaluated by a validated HPLC‐FL method. An infrared thermal stimulus was applied to the plantar surface of the turtles' hindlimbs to evaluate the thermal withdrawal latency (TWL). The two PK profiles of tramadol differed in the first 2 h following administration, but overlapped in the elimination phases. The metabolite M1 was formed in both the treatment groups, showing similar pharmacokinetic trends, although the amount of M1 was significantly higher (20%) in the hindlimb vs. forelimb group. Turtles given tramadol in the hind‐ and forelimb showed a significant increase in TWL over the periods of 0.5–48 and 8–48 h, respectively. The calculated % maximal possible response (% MPR) was low (about 24%). The PK/PD correlations between M1 plasma concentrations vs. % MPR appeared to show a counterclockwise hysteresis loop shape.     

Pharmacokinetic profiles of the analgesic flupirtine in dogs after the administration of four pharmaceutical formulations

ObjectiveFlupirtine (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 designFour-treatment, single-dose, four-phase, unpaired, cross-over design (4 × 4 Latin-square).AnimalsSix adult Labrador dogs.MethodsAnimals 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.ResultsAdverse 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 relevanceThis study provides pharmacokinetic data that can be used to design further studies to investigate FLU in dogs.     

Potential productivity of fibre hemp in southern Europe

Summary Hemp cultivation is not new to the southern regions, but cultivated area is decreasing. Recently, there has been a rediscovery of this crop, as a result of requests from the producers of natural fibres.The paper synthesizes the studies recently set up in southern Italy, with the goal of evaluating the adaptation and the yield of recent genotypes and of new agronomic techniques. The study demonstrates that, with the exception of the monoicious cultivars, the new genotypes of hemp are adapted to the environmental conditions of the Mediterranean Europe, reaching productive standards not lower than those obtained in other environments.The use of irrigation is indispensable for overcoming the prolonged water deficit which hemp is subject to during its cultivation cycle. A good irrigation practice consists in the partial satisfaction of the water requirements. The experimental evidence indicates that the best productive results are obtained with the reintegration of 66% of the water lost through evapotranspiration.A further saving in water is obtained with the anticipation of the sowing period, with, however, a loss in productive potential.Hemp can be considered, in all respects, a species to reintroduce in the current cultivation systems of southern Europe. It will be possible to increase its potential provided that breeding supplied new varieties, more tolerant to low temperatures (in order to anticipate the sowing time), and able to obtain economically profitable yields with the use of limited irrigation.     

Identification of a new genotype of canine distemper virus circulating in America

Canine Distemper is a highly contagious viral systemic disease that affects a wide variety of terrestrial carnivores. Canine Distemper virus (CDV) appears genetically heterogeneous, markedly in the hemagglutinin protein (H), showing geographic patterns of diversification that are useful to monitor CDV molecular epidemiology. In Mexico the activity of canine distemper remains high in dogs, likely because vaccine prophylaxis coverage in canine population is under the levels required to control effectively the disease. By phylogenetic analysis based on the nucleoprotein (N) and on the H genes, Mexican CDV strains collected between 2007 and 2010 were distinguished into several genovariants, all which constituted a unique group, clearly distinct from field and vaccine strains circulating worldwide, but resembling a CDV strain, 19876, identified in Missouri, USA, 2004, that was genetically unrelated to other North-American CDV strains. Gathering information on the genetic heterogeneity of CDV on a global scale appears pivotal in order to investigate the origin and modalities of introduction of unusual/novel CDV strains, as well as to understand if vaccine breakthroughs or disease epidemics may be somewhat related to genetic/antigenic or biological differences between field and vaccine strains.     

Toxicity and outcome in cats with oral squamous cell carcinoma after accelerated hypofractionated radiotherapy and concurrent systemic treatment

Recently, a multimodal approach to oral squamous cell carcinoma (SCC) in cats, combining medical treatment and accelerated radiation therapy, showed a substantial outcome improvement in a small pilot study. Herein we retrospectively review 51 cats with unresectable, histologically confirmed oral SCC and a complete initial staging work‐up: cats in group A (n = 24) received medical anti‐angiogenic treatment consisting of bleomycin, piroxicam and thalidomide, cats in group B (n = 27) received the anti‐angiogenic treatment and concurrent accelerated hypofractionated radiation therapy with 48Gy delivered in 10 fractions. Overall median progression‐free interval (PFI) was poor with 70 days (95% CI: 48;93). In the irradiated cats (group B), however, PFI was significantly longer with 179 days (95% CI: 58;301) days, vs 30 days (95% CI: 23;38) in medically only treated cats (P < .001). Overall median overall survival (OS) was 89 days (95% CI: 55;124), again significantly longer in the irradiated cats (group B) with 136 (95% CI: 40;233) vs 38 days (95% CI: 23;54) (P < .001). In 8 of the 27 (29.6%) cats in group B, however, severe toxicity (grade 3) occurred. Neither onset nor severity of toxicity could be associated with any of the tested variables, including anatomic site, tumour size, clinical stage and duration of neoadjuvant medical treatment. Given the potential severe acute effects and the impact on quality of life after chemo‐radiotherapy, owners must be clearly informed about the risks of treatment. With the overall poor outcome and high occurrence of acute toxicity, we cannot recommend the use of this accelerated radiation protocol combined with anti‐angiogenic therapy for oral SCC in cats.     

Fingerprinting Hydrocarbons in a Contaminated Soil from an Italian Natural Reserve and Assessment of the Performance of a Low-Impact Bioremediation Approach

An environmentally friendly procedure suitable to restore a protected area was evaluated at laboratory scale. Soil contaminated by high molecular weight (C > 10) aliphatic hydrocarbons and by chromium was withdrawn from the study site and a qualitative study of soil hydrocarbon components was first performed in order to assess the potential source of contamination. To this aim, a number of characteristic diagnostic ratios of hydrocarbon components were derived by processing chromatographic data, and were used as indicators for distinguishing anthropogenic from natural hydrocarbons. Then, the efficiency of landfarming for soil remediation was tested by comparing the effect of a few selected amendments and by monitoring the fate of chromium. Soil microbial abundance and activity were also evaluated. Results showed that soil hydrocarbons were mainly of anthropogenic origin and land treatment allowed effective degradation by native microbial populations even in the absence of amendments. The investigated procedures had no effect on the mobilisation of chromium that remained in its stable form of Cr(III). Conventional land treatment may therefore be an effective and safe procedure for the removal of hydrocarbons even in the presence of chromium, and may be applied to areas where low-impact procedures are strictly required.     

Evaluating the suitability of field beans as a substitute for soybean meal in early-lactating dairy cow: Production and metabolic responses

Twenty-four multiparous Holstein cows were utilized in a completely randomized design to examine the effect of feeding field beans (FB, Vicia faba L. var. minor) as substitute for soybean meal (SBM) on lactation performance and metabolic response during the early lactation period. Cows were individually divided into two equal groups and fed for 16 weeks on one each of the two experimental diets. The controls were fed pelleted concentrate contained 150 g/kg dry matter (DM) of SBM as the main protein source, whereas the experimental concentrate contained 345 g/kg DM of FB. Oat hay was offered ad libitum to cows and water was freely available. Blood samples were assayed for their content of: urea, glucose, triglycerides, cholesterol, total protein, albumin, calcium and phosphorus, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA). Inclusion of FB had no detectable effects on DM intake (DMI), body weight (BW), or body condition score (BCS). Neither milk yield nor quality were influenced by dietary treatment, except for milk urea nitrogen (MU) that was reduced in cows fed the FB diet (P < 0.05). Clotting properties of milk were not affected adversely by added dietary FB. Concentration of blood urea (BU) was lower in cows fed the FB diet than in those fed the control SBM diet (P < 0.05). These findings indicate that feeding FB in a lactation diet supported lactation performance similar to cows fed traditional SBM-based diet, and the results may elicit great interest for countries where soybean utilization is adversely influenced by high supply costs.     

Free and bound minor polar compounds in oats: Different extraction methods and analytical determinations

The extraction capacity of several solvent mixtures and comparison between alkaline and acid hydrolysis to extract free and bound minor polar compounds in oat samples were carried out. The extraction yield of each method was evaluated by correlating several spectrophotometric indices (absorption at 320 nm and total phenolic compounds by the Folin–Ciocalteu method) with HPLC-MS and the antioxidant activities of the oat extracts (DPPH radical method). The results showed that methanol and alkaline hydrolysis reported the highest recovery of polar compounds, and spectrophotometric indices overestimated the content of these compounds. Antioxidant compounds of five Romanian oat samples, named Comun, Jeremy, Mures, Lovrin 1, Lovrin 27-T were determined. Large intervarietal differences in phenolic compounds and their antioxidant activities among oat varieties were detected. Total minor polar contents content was in the range of 1179.47 and 1897.18 mg/kg of seed. According to the literature, we found that the majority of the minor polar compounds existed in bound form.