Evaluation of three novel azasterols against Toxoplasma gondii

Previous studies from our group have demonstrated the high susceptibility of Toxoplasma gondii tachyzoites to the sterol analogues 22,26-azasterol and 24,25-(R,S)-epiminolanosterol. In this work we present data on testing in vitro three novel azasterols as potential agents for the treatment of toxoplasmosis. The three compounds inhibited parasite growth at micromolar concentrations, in a dose-dependent manner. Electron microscopy analysis of intracellular tachyzoites after treatment with the most effective compound showed drastic mitochondrion swelling associated with the appearance of an electron-lucent matrix and disrupted cristae. Parasite lysis also took place. The appearance of electron dense cytoplasmic structures similar to amylopectin granules distributed throughout the parasite suggests that azasterols might be inducing differentiation of those tachyzoites which were not lysed to the bradyzoite stage.     

Finite element analysis of a novel pin-sleeve system for external fixation of distal limb fractures in horses

The transfixation pin cast (TPC) is an external skeletal fixation technique used to treat horses with distal limb fractures, but its use is often associated with pin-loosening and an increased risk of treatment failure. To address implant loosening, the pin sleeve cast system (PSC) was recently designed and consists of a pin-sleeve unit inserted into the bone. Each pin runs through a sleeve placed in the bone, making contact at two fixed points only within the sleeve. Each pin is attached to a ring embedded in a resin cast. In this report, the mechanical performance of a traditional TPC pin arrangement was compared with that of the PSC using validated finite element models of bone substitutes previously tested in vitro. The PSC resulted in a marked reduction in peak strain magnitude around the pins and a more even distribution of strain across the bone cortex. The two systems resulted in comparable proximal fragment displacement and had a similar stress concentration around bone defects during implant removal. The findings suggest that the PSC load transfer mechanism is effective even in geometrically complex structures like equine bones.     

A possible solution to model nonlinearity in elimination and distributional clearances with α2‐adrenergic receptor agonists: Example of the intravenous detomidine and methadone combination in sedated horses

The alpha(α)₂‐agonist detomidine is used for equine sedation with opioids such as methadone. We retrieved the data from two randomized, crossover studies where detomidine and methadone were given intravenously alone or combined as boli (STUDY 1) (Gozalo‐Marcilla et al., 2017, Veterinary Anaesthesia and Analgesia, 2017, 44 , 1116) or as 2‐hr constant rate infusions (STUDY 2) (Gozalo‐Marcilla et al., 2019, Equine Veterinary Journal, 51 , 530). Plasma drug concentrations were measured with a validated tandem Mass Spectrometry assay. We used nonlinear mixed effect modelling and took pharmacokinetic (PK) data from both studies to fit simultaneously both drugs and explore their nonlinear kinetics. Two significant improvements over the classical mammillary two‐compartment model were identified. First, the inclusion of an effect of detomidine plasma concentration on the elimination clearances (Cls) of both drugs improved the fit of detomidine (Objective Function Value [OFV]: ?160) and methadone (OFV: ?132) submodels. Second, a detomidine concentration‐dependent reduction of distributional Cls of each drug further improved detomidine (OFV: ?60) and methadone (OFV: ?52) submodel fits. Using the PK data from both studies (a) helped exploring hypotheses on the nonlinearity of the elimination and distributional Cls and (b) allowed inclusion of dynamic effects of detomidine plasma concentration in the model which are compatible with the pharmacology of detomidine (vasoconstriction and reduction in cardiac output).     

Effect of oxygen deficiency on uptake of water and mineral nutrients by tomato plants in soilless culture

The consequences of oxygen deficiency on the root system of tomato plants in soilless culture at the beginning of the flowering stage were assessed over a 72‐hour period. The study of water uptake and oxygen depletion in the medium was conducted using a process of continuous computerized data processing. Fluctuations in composition of the nutrient solution were monitored every two hours through an analysis of samples. Oxygen deficiency of the nutrient solution had immediate effects on the water and nutrient uptake of the whole plant. The root asphyxia of a tomato plant caused a 20 to 30% decrease of water uptake after 48 hours. After 10 hours it also leads to the end of the uptake process of the nutrients except nitrates. Potassium (K) was the nutrient most sensitive to oxygen deprivation since an efflux into the culture medium was observed after only 4 hours of deprivation. Nitrate uptake was the least affected by oxygen deficiency. The persistent appearance of nitrite in the culture medium 12 hours after the beginning of the asphyxia process could be caused by the reduction of nitrates by the root system of the tomato plant. The plant would use the oxygen from the reduction reaction to ensure the water and nitrate uptake processes which are the two most important limiting factors of plant nutrition. Thus it seems that under root asphyxia conditions the plant would adapt to the new condition by relying on a metabolism of the “nitrate respiration”; type.     

Conducting sustainability impact assessments of forestry-wood chains: examples of ToSIA applications

Within the EFORWOOD project, new methodological approaches to assess the sustainability impacts of forestry-wood chains (FWC) were developed by using indicators of environmental, social and economic relevance. This paper introduces and discusses the developed approach and the two main products developed in the EFORWOOD project: the Database Client and the Tool for Sustainability Impact Assessment (ToSIA), which hold, calculate and integrate the extensive information and data collected. Sustainability impact assessment (SIA) of FWCs is based on measuring and analysing environmental, economic and social indicators for all of the production processes along the value chain. The adoption of the method varies between applications and depends on the specification of the FWC in the assessment and what questions are studied. ToSIA is very flexible and can apply forest-, product-, industry- and consumer-defined perspectives. Each perspective influences the focus of the analysis and affects system boundaries. ToSIA can assess forest value chains in different geographical regions covering local, regional, national and up to the continental scale. Potential issues and scenarios can be analysed with the tool including, for example, the impacts of different forest policies on the sustainability of an FWC. This paper presents how ToSIA can be applied to solve such diverse problems and underlines this with examples from different case studies. Differences in chain set-up, system boundaries and data requirements are highlighted and experiences with the implementation of the sustainability impact assessment methods are discussed. The EFORWOOD case studies offer valuable reference data for future sustainability assessments.     

Epidural migration of new methylene blue in 0.9% sodium chloride solution or 2% mepivacaine solution following injection into the first intercoccygeal space in foal cadavers and anesthetized foals undergoing laparoscopy

OBJECTIVE: To determine the relationship between epidural cranial migration and injectate volume of an isotonic solution containing dye in laterally recumbent foal cadavers and evaluate the cranial migration and dermatome analgesia of an epidural dye solution during conditions of laparoscopy in foals. ANIMALS: 19 foal cadavers and 8 pony foals. PROCEDURES: Foal cadavers received an epidural injection of dye solution (0.05, 0.1, 0.15, or 0.2 mL/kg) containing 1.2 mg of new methylene blue (NMB)/mL of saline (0.9% NaCl) solution. Length of the dye column and number of intervertebral spaces cranial and caudal to the injection site were measured. Anesthetized foals received an epidural injection of dye solution (0.2 mL/kg) containing saline solution or 2% mepivacaine. Foals were placed in a 100 head-down position, and pneumoperitoneum was induced. Dermatome analgesia was determined by use of a described electrical stimulus technique. Foals were euthanatized, and length of the dye column was measured. RESULTS: Epidural cranial migration of dye solution in foal cadavers increased with increasing volume injected. No significant difference was found in epidural cranial migration of a dye solution (0.2 mL/kg) between anesthetized foals undergoing conditions of laparoscopy and foal cadavers in lateral recumbency. Further craniad migration of the dye column occurred than indicated by dermatome analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural cranial migration increases with volume of injectate. On the basis of dermatome analgesia, an epidural injection of 2% mepivacaine (0.2 mL/kg) alone provides analgesia up to at least the caudal thoracic dermatome and could permit caudal laparoscopic surgical procedures in foals.     

Comparison of two laparoscopic suture patterns for repair of experimentally ruptured urinary bladders in normal neonatal calves

OBJECTIVE: To compare 2 laparoscopic suture patterns for repair of experimentally ruptured urinary bladders in normal neonatal calves. STUDY DESIGN: Experimental surgical study. ANIMALS: Thirty male Holstein calves. METHODS: A bladder defect was created in 24 anesthetized calves (day 0). They were randomly divided into 4 groups (n=6/group). In groups 1 and 3, the defect was closed laparoscopically using a one layer full thickness simple continuous (FTSC) suture pattern (pattern A). In groups 2 and 4, the defect was closed laparoscopically in 2 layers using a FTSC suture pattern followed by Lembert continuous suture pattern (pattern B). Groups 1 and 2 calves were euthanatized at the end of the surgery and groups 3 and 4 at day 10. Six healthy calves were also euthanatized and used as a control group. The bladders were harvested and tested for bursting strength (BS). The surgical time (ST) data from the two groups for each pattern were pooled. A Student t-test was used to compare ST data. For the BS data, a 2-factor ANOVA test with post-hoc Student t-test was used to determine if treatment, time, or treatment-time interaction was significant. A Dunnett's test was used to compare BS of the 4 treatment groups to the control group. P<.05 was considered significant. RESULTS: Mean ST was significantly shorter for pattern A than for pattern B. In all treatment groups, the mean bladder BS (MBBS) was significantly lower than the MBBS for the control group. The MBBS was significantly lower for group 1 than for group 2. There was no significant difference in the MBBS between groups 3 and 4. CONCLUSION: In this study, a 1-layer laparoscopic closure technique had advantages compared with 2-layer laparoscopic closure technique. Further work is required before a 1-layer laparoscopic closure technique can be recommended clinically. CLINICAL RELEVANCE: One-layer bladder closure is fast and safe in clinically normal calves and permits additional research to evaluate its safety in foals and clinical ruptures.     

Cylindrical press-fit osteochondral allografts for resurfacing the equine metatarsophalangeal joint

OBJECTIVE: To investigate the feasibility of resurfacing the equine fetlock joint using cylindrical, orthotopic, press-fit, osteochondral allografts. STUDY DESIGN: Experimental study. ANIMALS: Ten mature, mixed-breed horses. METHODS: Cylindrical, osteochondral grafts (6.5-mm diameter) were harvested aseptically from cadaveric equine metatarsophalangeal joints. Allografts were transplanted into 6 horses; 4 horses were sham operated. The surgical approach involved creation of a bone block at the origin of the medial collateral ligament and luxation of the metatarsophalangeal joint. Grafts were placed into the medial and lateral metatarsal condyles. Radiographs were taken at 8 and 25 weeks, and lameness was evaluated at 25 weeks. Horses were killed at 25 weeks. Analyses included gross evaluation, microradiography, paravital staining, light microscopy, and cartilage biochemistry. RESULTS: No complications occurred that could be attributed to the surgical procedure. Graft congruency with the surrounding articular cartilage was fair to excellent. Two horses were sound at 25 weeks. Most grafts had more than 90% articular cartilage coverage, and histologic and microradiographic analysis revealed good graft incorporation and articular cartilage survival. Sulphated glycosaminoglycan concentration was decreased in grafted tissue. CONCLUSIONS: We attribute the viability of osteochondral allografts in the equine fetlock to adequate congruency, stable graft fixation, and the use of orthotopic tissue. Host response to the allograft bone tissue did not affect cartilage viability. CLINICAL RELEVANCE: Before clinical use, improvements to instrumentation are required that would decrease damage to grafts and minimize technique-associated incongruencies of the articular surface at the time of grafting. Larger grafts would also likely be required to resurface a greater surface area.