Sulfated ferulic acid is the main in vivo metabolite found after short-term ingestion of free ferulic acid in rats

The bioavailability of ferulic acid (FA; 3-methoxy-4-hydroxycinnamic acid) and its metabolites was investigated in rat plasma and urine after an oral short-term ingestion of 5.15 mg/kg of FA. Free FA, glucuronoconjugates, and sulfoconjugates were quickly detected in plasma with a peak of concentration found 30 min after ingestion. Sulfoconjugates were the main derivates ( approximately 50%). In urine, the cumulative excretion of total metabolites reached a plateau 1.5 h after ingestion, and approximately 40% were excreted by this way. Free FA recovered in urine represented only 4.9 +/-1.5% of the native FA consumed by rats. Glucuronoconjugates and sulfoconjugates represented 0.5 +/- 0.3 and 32.7 +/- 7.3%, respectively. These results suggested that a part of FA incorporated in the diet was quickly absorbed and largely metabolized in sulfoconjugates before excretion in urine.     

Genotype by environment interactions (GEIs) for barley grain yield under salt stress condition

Changes in the relative genetic performance of genotypes across environments are referred to as genotype × environment interactions (GEIs). GEIs can affect barley breeding improvement for salt tolerance because it often complicates the evaluation and selection of superior genotypes. The present study evaluated the GEIs over 60 barley genotypes for yield components and grain yield in six salinity environments in North Delta, Egypt. Data were analyzed using the additive main effects and multiplicative interaction (AMMI) and Tai’s stability parameters. GEIs effects on yield explained 20.3, 20.1, 14.6, and 33.0% of the total variation besides, the first two principal components account for 67.3, 56.3, 64.3, and 83.7% of the explained variance in the four sets, respectively. Six genotypes namely G-4, G-7, G-20, G-34, G-36, and G-39 were found to be most stable and high yielding across environments (GY >2.00 t ha^-1), and located close to zero projection onto the AEC ordinate. Tai’s stability parameters demonstrated that these genotypes were more responsive to the environmental changes. The genotypes G-50 and G-53 showed perfect/static stability (α = -0.95, -0.91, respectively). In contrast, the genotype; G-36 had α = 0 and λ = 1.10, indicating parallel with the environmental effects followed by G-44. Overall, we found that GEIs for grain yield are highly significant in all sets, suggesting that responded differently across environments. This interaction may be a result of changes in genotypes’ relative performance across environments, due to their differential responses to various abiotic factors.     

Predicting summer fin whale distribution in the Pelagos Sanctuary (north-western Mediterranean Sea) to identify dynamic whale–vessel collision risk areas

1. Mediterranean fin whales aggregating in the Pelagos Sanctuary in summer to feed are exposed to vessel collision risk, particularly from high-speed ferries.
2. This study developed models to predict summer fin whale distribution using a generalized additive model (GAM) and MaxEnt, with the aim of providing a tool to identify potential high whale–ferry collision risk areas along ferry routes within the Pelagos Sanctuary during summertime.
3. Models were trained using sightings data collected in the summer months of 2009–2018 on board ferries crossing the central area of the Pelagos Sanctuary. Environmental predictors were bathymetry and mean sea surface chlorophyll concentration of the annual spring bloom period.
4. The predictive ability of GAM and MaxEnt was assessed using existing knowledge of summer fin whale distribution in the region. GAM (deviance explained = 20.2%) predictions matched documented distributions more closely than that of MaxEnt, with highest predicted fin whale occurrence in deep offshore waters (>2000 m) encompassing the central north-western and western regions, and in the south-eastern region, consistent with known fin whale habitats within the Pelagos Sanctuary. Inter-annual variability was evident, influencing collision risk areas.
5. Collision risk was estimated as a function of the overlap between the predicted probability of fin whale occurrence and ferry density estimated from Automated Identification System data. Ferry routes that cross the northern and eastern regions of the Pelagos Sanctuary presented relatively higher collision risk.
6. Areas with changes in risk intensity between the years were temporally and spatially dynamic: some appeared intermittently throughout the study period while others persisted over consecutive years or recurred in different years.
7. Due to the vastness of the Pelagos Sanctuary, vessel speed reduction maybe a more practical measure to manage collision risk than re-routing shipping lanes. A combination of Seasonal Management Areas and Dynamic Management Areas approaches could be adopted for high-risk areas.

     

Differential susceptibility to tetracycline,oxytetracycline and doxycycline of the calf pathogens Mannheimia haemolytica and Pasteurella multocida in three growth media

For clinical isolates of bovine Mannheimia haemolytica and Pasteurella multocida, this study reports minimum inhibitory concentration (MIC) differences for tetracycline, oxytetracycline and doxycycline between cation‐adjusted Mueller‐Hinton broth (CAMHB), foetal bovine serum (FBS) and Roswell Park Memorial Institute (RPMI) medium. MICs were determined according to CLSI standards and additionally using five overlapping sets of twofold dilutions. Matrix effect: (a) free drug MICs and minimum bactericidal concentrations (MBC) for all drugs were significantly higher in FBS than in CAMHB for both pathogens (p < 0.001); (b) MICs and MBCs were higher for CAMHB and FBS compared to RPMI for P. multocida only. Net growth rate for P. multocida in CAMHB was significantly slower than in FBS and higher than in RPMI, correlating to MIC and MBC ranking. Drug effect: doxycycline MICs and MBCs were significantly lower (p < 0.001) in both CAMHB and FBS than tetracycline and oxytetracycline for both pathogens. Only for M. haemolytica were oxytetracycline MIC and MBC significantly lower than tetracycline, precluding the use of tetracycline to predict oxytetracycline susceptibility in this species. Determining potencies of tetracyclines in a physiological medium, such as FBS, is proposed, when the objective is correlation with pharmacokinetic data for dosage determination.     

Intraosseous gentamicin perfusion of the distal metacarpus in standing horses

OBJECTIVE: To report tissue gentamicin concentrations after intraosseous (IO) perfusion in standing horses. STUDY DESIGN: In vivo study. ANIMALS OR SAMPLE POPULATION: Twelve horses. METHODS: Sedated horses had a cannulated cortical bone screw inserted into the dorsolateral aspect of the treated metacarpus and a tourniquet applied proximally. Gentamicin (2.2 mg/kg) diluted in sterile saline solution (0.1 mL/kg) was infused through the screw. Two horses were euthanatized at each time interval: 0, 2, 6, 12, 24, and 36 hours. Synovial fluid and bone samples were collected distal to the screw from both forelimbs. Gentamicin concentrations were measured using fluorescence polarization immunoassay. RESULTS: The highest synovial fluid gentamicin concentrations were 385+/-273 microg/mL (mean+/-SD) in the metacarpophalangeal joint, 225+/-205 microg/mL in the proximal interphalangeal joint, 215+/-205 microg/mL in the distal interphalangeal joint, 382+/-195 microg/mL in the digital flexor tendon sheath, and 206+/-161 microg/mL in the navicular bursa. The highest bone concentrations of gentamicin were 55+/-30 microg/g in the distal metacarpus, 34+/-27 microg/g in the proximal, 16+/-15 microg/g in the middle, and 16+/-2.2 microg/g in the distal phalanges, and 27+/-17 microg/g in the proximal and 24+/-11 microg/g in the distal sesamoid bones. CONCLUSION: Standing IO perfusion of gentamicin resulted in local antibiotic concentrations in the synovial structures and bones of the distal aspect of the limb that exceed the reported minimum inhibitory concentration of pathogens commonly implicated in equine orthopedic infections. CLINICAL RELEVANCE: Standing IO perfusion of gentamicin in the distal aspect of the limb should be considered for treatment of orthopedic infections of this region in horses.     

Use of Electrocautery Probes in Arthroscopic Removal of Apical Sesamoid Fracture Fragments in 18 Standardbred Horses

OBJECTIVE: To develop a technique for arthroscopic excision of apical sesamoid fracture fragments using electrocautery probes. ANIMALS OR SAMPLE POPULATION: A total of 18 Standardbred horses. METHODS: Arthroscopic removal of apical sesamoid fracture fragments using both hook and loop electrocautery probes was performed on 18 Standardbred horses. The fracture fragments were approached using either an ipsilateral (3) or contralateral (15) arthroscopic triangulation technique. Distension of the metacarpo- (metatarso)-phalangeal joints was achieved using a 1.5% glycine solution. Under arthroscopic guidance, both the suspensory and intersesamoidean ligament attachments to the abaxial and the axial margins of the apical fragment were transected using a hook electrocautery probe. Subsequently, the palmar (plantar) soft tissue attachments to the apical fragment were transected with a loop electrocautery probe. Once freed of soft tissue attachments, the apical fragment was removed with Ferris-Smith intervertebral disc rongeur. The arthroscopic portals were closed in a routine manner. RESULTS: Horse ages ranged from 2 to 8 years (median, 2.5 years). Eighteen apical sesamoid fracture fragments were removed from the left (8) and right (8) hind limbs and the left (1) and right (1) forelimbs. Apical fragments occured in 15 lateral and 3 medial proximal sesamoid bones. No major complications occurred during or after surgery. The electrocautery probes permitted an easy and precise dissection of all soft tissue attachments to the apical sesamoid fracture fragments in all horses. Follow-up time was 7 to 44 months (median, 26 months); 10 of 14 horses returned to racing. Seven of nine horses that raced before surgery raced again and three of five that had not raced before surgery, raced afterwards. CONCLUSION: Arthroscopic excision of apical sesamoid fracture fragments can be accomplished arthroscopically using electrocautery probes. CLINICAL RELEVANCE: Arthroscopic electrosurgery is an efficient and safe alternative for intra-articular dissection in horses.     

Pharmacokinetic and pharmacodynamic modelling of intravenous,intramuscular and subcutaneous buprenorphine in conscious cats

ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg^?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t_1/2k_e0 = 47.4 minutes) and receptor binding (k_on = 0.011 mL ng^?1 minute^?1). Persistence of thermal antinociception was due to slow receptor dissociation (t_1/2k_off = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats.