Pharmacokinetic and urine profile of tramadol and its major metabolites following oral immediate release capsules administration in dogs

The aim of the present paper was to test the oral administration of oral immediate release capsules of tramadol in dogs, to asses both its pharmacokinetic properties and its urine profile. After capsules administration of tramadol (4 mg/kg), involving eight male Beagle dogs, the concentration of tramadol and its main metabolites, M1, M2 and M5, were determined in plasma and urine using an HPLC method. The plasma concentrations of tramadol and metabolites were fitted on the basis of mono- and non-compartmental models, respectively. Tramadol was detected in plasma from 5 min up to 10 h in lesser amounts than M5 and M2, detected at similar concentrations, while M1 was detected in negligible amounts. In the urine, M5 and M1 showed the highest and smallest amount, respectively; M1 and M5 resulted widely conjugate with glucuronic acid. In conclusion, after oral administration of tramadol immediate release capsules, the absorption of the active ingredient was rapid, but its rapid metabolism quickly transformed the parental drug to high levels of M5 and M2, showing an extensive elimination via the kidney. Hence, in the dog, the oral immediate release pharmaceutical formulation of tramadol would have different pharmacokinetic behaviour than in humans.     

A genetic variant near the equine interleukin 6 gene associated with copper:zinc ratio

The aim of this study was to validate an A/T single nucleotide polymorphism (SNP) corresponding to a LINE2 sequence located ～1.1kb downstream of the IL-6 gene (SNP BIEC2-911738) and to determine if this variant is correlated with interleukin 6 (IL-6) modulation or with different plasma concentrations of Zn, Cu, Se and Fe. The frequency of the newly described variant T ranged from 0 to 23.1% among different breeds of horses. SBIEC2-911738 was not associated with changes in IL-6 plasma levels. Increased Cu:Zn ratios were observed in horses carrying the AT genotype independently of breed when stabled for 24h after physical exercise.     

Missing OH reactivity in a forest: evidence for unknown reactive biogenic VOCs

Forest emissions of biogenic volatile organic compounds (BVOCs), such as isoprene and other terpenes, play a role in the production of tropospheric ozone and aerosols. In a northern Michigan forest, the direct measurement of total OH reactivity, which is the inverse of the OH lifetime, was significantly greater than expected. The difference between measured and expected OH reactivity, called the missing OH reactivity, increased with temperature, as did emission rates for terpenes and other BVOCs. These measurements are consistent with the hypothesis that unknown reactive BVOCs, perhaps terpenes, provide the missing OH reactivity.     

Concentrations of platelet α2-adrenoceptors,lymphocyte muscarinic receptors,and blood monoamines in dogs (Canis familiaris) affected by canine cognitive dysfunction syndrome

Canine cognitive dysfunction syndrome (CDS) is a neurodegenerative disorder of aged dogs characterized by a progressive decline in cognitive function. In humans and laboratory animals, a variety of neurotransmitter abnormalities have been described in patients affected by age-related dementia. Specifically, the regulatory role of the catecholaminergic, serotonergic, and cholinergic systems has been outlined. The aim of the present study was to measure blood monoamine levels, platelet α₂-adrenergic receptors, and lymphocyte muscarinic receptors in healthy adult and aged dogs and in dogs affected by canine cognitive dysfunction. Based on clinical and behavioral examination, 40 dogs were divided into 3 groups: healthy adults (n = 14), aged dogs (n = 17), and aged dogs affected by canine cognitive dysfunction (n = 9). A significant reduction in plasma levels of norepinephrine and dopamine was observed both in aged dogs (0.16 ± 0.02 ng/mL, P < 0.01; 0.11 ± 02 ng/mL, P < 0.01, respectively) and in CDS dogs (0.14 ± 0.03 ng/mL, P < 0.05; 0.10 ± 00.005 ng/mL, P < 0.01, respectively) compared with adults (0.29 ± 0.04 ng/mL and 0.15 ± 0.02 ng/mL, respectively). No significant differences were observed among groups for α₂-adrenergic receptor concentrations. Canine lymphocytes express 2 distinct classes of muscarinic receptors, characterized by high (HA) and low affinity (LA) for [³H]-N-methyl-scopolamine. A significant age-dependent decrease in HA muscarinic receptors was observed. However, no differences were found between aged dogs (87.65 ± 11.08 sites/cell × 10²) and in CDS dogs (90.17 ± 6.75 sites/cell × 10² ) for HA muscarinic receptor concentrations. As far as LA muscarinic receptors are concerned, CDS dogs showed a significant increase (393.48 ± 63 sites/cell × 10²; P < 0.05) with respect to healthy adult dogs (188.84 ± 16.50 sites/cell × 10²). Our results suggest that the reduction in HA muscarinic receptor-binding sites could be representative of the physiological aging process, whereas the increase in lymphocyte LA muscarinic receptor levels could be related to the cognitive decline.     

Sensory nerve conduction and nociception in the equine lower forelimb during perineural bupivacaine infusion along the palmar nerves

The purpose of this investigation was to study lateral palmar nerve (LPN) and medial palmar nerve (MPN) morphology and determine nociception and sensory nerve conduction velocity (SNCV) following placement of continuous peripheral nerve block (CPNB) catheters along LPN and MPN with subsequent bupivacaine (BUP) infusion. Myelinated nerve fiber distribution in LPN and MPN was examined after harvesting nerve specimens in 3 anesthetized horses and processing them for morphometric analysis. In 5 sedated horses, CPNB catheters were placed along each PN in both forelimbs. Horses then received in one forelimb 3 mL 0.125% BUP containing epinephrine 1:200 000 and 0.04% NaHCO(3) per catheter site followed by 2 mL/h infusion over a 6-day period, while in the other forelimb equal amounts of saline (SAL) solution were administered. The hoof withdrawal response (HWR) threshold during pressure loading of the area above the dorsal coronary band was determined daily in both forelimbs. On day 6 SNCV was measured under general anesthesia of horses in each limb's LPN and MPN to detect nerve injury, followed by CPNB catheter removal. The SNCV was also recorded in 2 anesthetized non-instrumented horses (sham controls). In both LPN and MPN myelinated fiber distributions were bimodal. The fraction of large fibers (>7 μm) was greater in the MPN than LPN (P < 0.05). Presence of CPNB catheters and SAL administration did neither affect measured HWR thresholds nor SNCVs, whereas BUP infusion suppressed HWRs. In conclusion, CPNB with 0.125% BUP provides pronounced analgesia by inhibiting sensory nerve conduction in the distal equine forelimb.     

Survey of mealybug (Hemiptera: Pseudococcidae) vectors of <Emphasis Type="Italic">Ampelovirus</Emphasis> and <Emphasis Type="Italic">Vitivirus</Emphasis> in vineyards of northwestern Italy

Mealybugs (Hemiptera: Pseudococcidae) are sap-sucking insects which infest a broad range of crops worldwide. They represent an important threat to viticulture as they are vectors of viruses associated with leafroll and rugose wood complex diseases. In this study, we surveyed the presence of mealybugs and their associated viruses in vineyards of the Piemonte and Liguria regions, northwestern Italy. In order to determine the collected specimens correctly, we added a species-specific marker for Heliococcus bohemicus to an existing molecular identification key. The only species collected in Piemonte was H. bohemicus, whereas in Liguria, H. bohemicus, Planococcus ficus and Pseudococcus longispinus were found; Ps. longispinus has never before been reported in Italian vineyards. Several specimens of all three species were infected by the ampeloviruses GLRaV-1 and GLRaV-3 and the vitivirus GVA. Both nymphs and adult females tested positive for the viruses and mixed infections were commonly found within the same insect. Population levels and virus incidence were higher in Liguria than in Piemonte, suggesting a greater risk of disease spread. We conclude that the mild, Mediterranean climate of Liguria favors the development of a diverse mealybug fauna while only H. bohemicus, known to be tolerant to the severe continental winter temperatures, colonize grapevines in colder viticultural areas.     

Soil type, management history, and soil amendments influence the development of soil-borne (Rhizoctonia solani, Pythium ultimum) and air-borne (Phytophthora infestans, Hyaloperonospora parasitica) diseases

The impact of soil type, long-term soil management, and short-term fertility input strategies on the suppressiveness of soils against soil-borne (Ocimum basilicum – Rhizoctonia solani, Lepidium sativum – Pythium ultimum) as well as air-borne (Lycopersicon esculentum – Phytophthora infestans, Arabidopsis thaliana – Hyaloperonospora parasitica) diseases was studied. Soils from field trials established in five European sites with contrasting pedo-climatic conditions were examined. Sites included (i) a long-term management field trial comparing organic and conventional farming systems (DOK-trial, Therwil, Switzerland) (ii) a short-term fertility input field trial comparing mineral and organic matter fertilisation regimes (Bonn (BON), Germany) (iii) two short-term fertility input field trials (Stockbridge (STC) and Tadcaster (TAD), UK) comparing the impact of farmyard manure, composted farmyard manure, and chicken manure pellet amendements and (iv) soil from a site used as a reference (Reckenholz (REC), Switzerland). Soil type affected disease suppressiveness of the four pathosystems signficantly, indicating that soils can not only affect the development of soil-borne, but also the resistance of plants to air-borne diseases at relevant levels. Suppressiveness to soil- and air-borne diseases was shown to be affected by soil type, but also by long-term management as well as short-term fertility inputs.     

Pharmacokinetics of tramadol and metabolites after injective administrations in dogs

The aim of this study was to determine the pharmacokinetics of tramadol and its main metabolites after i.v. and i.m. injections. The pharmacokinetic cross-over study was carried out on 6 healthy male beagle dogs. Tramadol was administered by intravenous (i.v.) and intramuscular (i.m.) injection at 4 mg/kg. Tramadol and its main metabolites O-desmethyl-tramadol (M1), N-,N-didesmethyl-tramadol (M2) and N-,O-didesmethyl-tramadol (M5) concentrations were measured in plasma samples by a HPLC coupled with fluorimetric detection; pharmacokinetic evaluations were carried out with a compartmental and non-compartmental model for tramadol and its metabolites, respectively. The bioavailability of the drug, ranging between 84-102% (mean 92%), was within the generally accepted values for a positive bioequivalence decision of (80-125%). After the i.m. injection the mean plasma drug concentration peak was reached after a T(max) of 0.34 h with a C(max) of 2.52 microg/mL. No therapeutic relevant differences were observed between i.m. and i.v. administration. The minimal effective plasma concentration was reached after a few minutes and maintained for about 6-7 h in both administrations. M1 plasma concentration was low and the amounts of the other metabolites produced were analogous in both routes of administration. In conclusion, tramadol was rapidly and almost completely absorbed after i.m. administration and its systemic availability was equivalent to the i.v. injection. The different onset time and duration of action observed were very small and probably therapeutically irrelevant. The i.m. injection is a useful alternative to i.v. injection in the dog.     

Group-type and fingerprint analysis of roasted food matrices (coffee and hazelnut samples) by comprehensive two-dimensional gas chromatography

The present study is focused on the volatile fraction of roasted hazelnut and coffee samples, differing in botanical origins, morphological characteristics, and roasting treatments, selected as challenging matrices. Volatile components, sampled by headspace solid phase microextraction (HS-SPME), were analyzed by GC x GC-qMS, and separation results were adopted to classify, correlate, and/or compare samples and evaluate processing effects. The high-complexity sample profiles were interpreted through different methods: a group-type characterization, a direct fingerprint comparison, and a template matching to extract useful and consistent information, and advantages and limits of each specific approach were critically evaluated. The group-type analysis, focused on several known botanical and technological markers, enabled sample comparison and characterization based on their quali-quantitative distribution; it is highly reliable, because of the authentic standard confirmation, and extends the comparative procedure to trace and minor components. Fingerprint approaches (i.e., direct fingerprint comparison and template matching), on the other hand, extended sample comparisons and correlations to the whole volatiles offering an increased discrimination potential and improved sensitivity due to the wider analyte pattern considered. This study demonstrates the ability of comprehensive GC to further explore the complexity of roasted samples and emphasizes the advantages of, and the need for, a comprehensive and multidisciplinary approach to interpret the increased level of information provided by GC x GC separation in its full complexity.