Sedative and analgesic effects of detomidine or detomidine and butorphanol in the donkey

There are approximately forty two million donkeys in the world. All developing countries have an expanding population of donkeys, which are used for the provision of various services. The most commonly performed procedures in donkeys are castrations, tumour removals, foot care and dental treatments. All of these procedures can be performed in standing donkeys provided sufficient analgesia and sedation are provided. The donkey should be recognised and treated in its own light. Very few analgesics relieve pain without producing side effects. The ideal analgesic would provide good analgesia and sedation without any side effects. Combined with sedation, analgesia aids in the handling of animals and reduces the danger to attendants. Neuroleptanalgesia provides a more potent sedative and analgesic allowing more procedures to be performed. A marked synergistic effect between opioids and alpha2 adrenergic agonists is reported. Detomidine-butorphanol is used extensively for equine sedation and analgesia in the United States of America and Europe. Currently there is limited information available on effective sedative and analgesic drugs or drug combinations in donkeys. Detomidine and xylazine, which belong to the alpha2 adrenergic agonist group, have been described for use in donkeys. No information exists on the use of opioid drugs or opioid-sedative combinations in donkeys. Detomidine produces sedation and analgesia of a greater magnitude and a longer duration than xylazine. Detomidine has been used to sedate horses for diagnostic, therapeutic or minor surgical procedures and as part of a premedication or an intravenous anaesthetic protocol. Detomidine is a good analgesic. The duration of sedation and analgesia is dose dependent. The sedation produced by detomidine alone is not always satisfactory and some horses will respond to noxious stimuli with well-directed kicks. For this reason, detomidine and butorphanol are very often combined. Butorphanol is a synthetic mixed agonist-antagonist opioid. The detomidine is given five minutes before the administration of butorphanol or the butorphanol can follow the detomidine. Sedation is easily extended by additional doses of detomidine and/or butorphanol. This combination produces profound sedation in which horses are apparently unaffected by sounds, tactile stimuli and surrounding activity. It has been suggested that donkeys require a higher dose of detomidine for sedation than horses. The recommended dose for donkeys is 20-40 µg/kg. The degree and length of analgesia and sedation is dose dependent. A dose of 5-10 µg /kg was found effective for sedation and a dose of 20 µg /kg was effective for sedation and analgesia. No recommended doses for butorphanol in donkeys exist. Twelve healthy male donkeys were randomly divided into two groups. One group received 10 µg/kg of detomidine while the other group received 10 µg /kg of detomidine and 25 µg /kg of butorphanol. Sedation was evaluated by a scoring system and characterised by lowering of the head, relaxation of the upper eyelids, drooping of the lower lip and dropping of the ears. Analgesia was evaluated by means of a pinprick method. The average dose for detomidine was 11.24 µg/kg and that of butorphanol was 28.0 µg/kg. The onset time to sedation was 4 minutes 21 seconds with detomidine alone and 3 minutes 28 seconds with the combination. The average length of sedation for the detomidine group was 20 minutes, and for the detomidine-butorphanol group was 1 hour and 7 minutes. The analgesia lasted twice as long in combination group compared to the detomidine group. Detomidine did not eliminate coronary band pain. Heart rates dropped significantly in the first minute after the injection in both groups, and this was statistically significant. There was however no statistical difference between the two groups. An atrioventricular and a sinoatrial block were recorded during this trial. The respiratory rates tended to decrease in the first few minutes after which the rate stabilised. Four donkeys receiving butorphanol had Cheyne-Stokes respiratory patterns. It was evident that the combination of detomidine and butorphanol produced a greater sedative and analgesic effect than detomidine alone. The superior sedation is the result of synergistic effects between detomidine and butorphanol. This trial has shown that detomidine in combination with butorphanol in donkeys produces sedation that is superior to detomidine on its own and last at least twice as long. Analgesia was dramatically improved with the combination as compared to detomidine alone.Dissertation (MMed Vet (Anaesthesiology))--University of Pretoria, 2000.Companion Animal Clinical Studiesunrestricte

Quantum Kinetic Rates within the Nonequilibrium Steady State

The nonequilibrium steady state (NESS) of a quantum network is central to a host of physical and biological scenarios. Examples include natural processes such as vision and photosynthesis, as well as technical devices such as photocells, both activated by incoherent light (e.g. sunlight) and leading to quantum transport. Here, a completely general approach to defining components of a quantum network in the NESS, and obtaining rates of processes between these components is provided. Quantum effects are explicitly included throughout, both in (a) defining network components via projection operators, and (b) in determining the role of coherences in rate processes. As examples, the methodology is applied to model cases, two versions of the V-level system, and to the spin-boson model, wherein the role of the environment and of internal system properties in determining the rates is examined. In addition, the role of Markovian vs. non-Markovian contributions is quantified, exposing conditions under which NESS rates can be obtained by perturbing the nonequilibrium steady state

Inhibition of mTORC1 Enhances the Translation of Chikungunya Proteins via the Activation of the MnK/eIF4E Pathway

International audienceChikungunya virus (CHIKV), the causative agent of a major epidemic spanning five continents, is a positive stranded mRNA virus that replicates using the cell's cap-dependent translation machinery. Despite viral infection inhibiting mTOR, a metabolic sensor controls cap-dependent translation, viral proteins are efficiently translated. Rapalog treatment, silencing of mtor or raptor genes, but not rictor, further enhanced CHIKV infection in culture cells. Using biochemical assays and real time imaging, we demonstrate that this effect is independent of autophagy or type I interferon production. Providing in vivo evidence for the relevance of our findings, mice treated with mTORC1 inhibitors exhibited increased lethality and showed a higher sensitivity to CHIKV. A systematic evaluation of the viral life cycle indicated that inhibition of mTORC1 has a specific positive effect on viral proteins, enhancing viral replication by increasing the translation of both structural and nonstructural proteins. Molecular analysis defined a role for phosphatidylinositol-3 kinase (PI3K) and MAP kinase-activated protein kinase (MnKs) activation, leading to the hyper-phosphorylation of eIF4E. Finally, we demonstrated that in the context of CHIKV inhibition of mTORC1, viral replication is prioritized over host translation via a similar mechanism. Our study reveals an unexpected bypass pathway by which CHIKV protein translation overcomes viral induced mTORC1 inhibition

Computed tomography determined changes in position of the hepatobiliary and gastrointestinal systems after CO2 insufflation to determine optimal positioning for abdominal laparoscopy

OBJECTIVE : To evaluate changes in body position and effect of CO2 insufflation on the hepatobiliary and gastrointestinal systems using computed tomography (CT) to determine optimal laparoscopic approach. STUDY DESIGN : Experimental study. ANIMALS : Healthy intact female Beagles (n = 6) of similar age, weight, and body condition score. METHODS : Urinalysis, peripheral blood smear, and abdominal ultrasonography were performed to determine dog health. A series of pre insufflation (PrI) CT scans in ventrodorsal routine (VDR), ventrodorsal Trendelenburg (VDT), left lateral (LL), and right lateral (RL) recumbency were performed before and after abdominal insufflation (PoI) with CO2 (10–14 mm Hg). Pre-determined measurements were made on PrI and PoI scans and differences compared.Results: Liver position was affected by body position and under gravitational influence moved to the dependent part of the abdominal cavity. The gallbladder was best exposed in LL. Stomach position was not significantly changed after insufflation. Different areas of small intestine were dependent on gravitational effects. The pancreas maintained a similar position after insufflation. CONCLUSIONS : VDR was the ideal position for all laparoscopic procedures of the liver. The LL position could be used for surgery of the gallbladder but likely provides poor exposure to the rest of the liver. In approaching the stomach and intestines, the area of interest should be used to determine the best position.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1532-950X2016-07-31hb2016Companion Animal Clinical StudiesParaclinical Science

Ultraviolet Imaging Polarimetry of the Large Magellanic Cloud. II. Models

Motivated by new sounding-rocket wide-field polarimetric images of the Large Magellanic Cloud, we have used a three-dimensional Monte Carlo radiation transfer code to investigate the escape of near-ultraviolet photons from young stellar associations embedded within a disk of dusty material (i.e. a galaxy). As photons propagate through the disk, they may be scattered or absorbed by dust. Scattered photons are polarized and tracked until they escape to be observed; absorbed photons heat the dust, which radiates isotropically in the far-infrared, where the galaxy is optically thin. The code produces four output images: near- UV and far-IR flux, and near-UV images in the linear Stokes parameters Q and U. From these images we construct simulated UV polarization maps of the LMC. We use these maps to place constraints on the star + dust geometry of the LMC and the optical properties of its dust grains. By tuning the model input parameters to produce maps that match the observed polarization maps, we derive information about the inclination of the LMC disk to the plane of the sky, and about the scattering phase function g. We compute a grid of models with i = 28 deg., 36 deg., and 45 deg., and g = 0.64, 0.70, 0.77, 0.83, and 0.90. The model which best reproduces the observed polarization maps has i = 36 +2/-5 degrees and g ~0.7. Because of the low signal-to-noise in the data, we cannot place firm constraints on the value of g. The highly inclined models do not match the observed centro-symmetric polarization patterns around bright OB associations, or the distribution of polarization values. Our models approximately reproduce the observed ultraviolet photopolarimetry of the western side of the LMC; however, the output images depend on many input parameters and are nonunique.Comment: Accepted to AJ. 20 pages, 7 figure

Deep learning diagnostics of gray leaf spot in maize under mixed disease field conditions

Maize yields worldwide are limited by foliar diseases that could be fungal, oomycete, bacterial, or viral in origin. Correct disease identification is critical for farmers to apply the correct control measures, such as fungicide sprays. Deep learning has the potential for automated disease classification from images of leaf symptoms. We aimed to develop a classifier to identify gray leaf spot (GLS) disease of maize in field images where mixed diseases were present (18,656 images after augmentation). In this study, we compare deep learning models trained on mixed disease field images with and without background subtraction. Performance was compared with models trained on PlantVillage images with single diseases and uniform backgrounds. First, we developed a modified VGG16 network referred to as “GLS_net” to perform binary classification of GLS, which achieved a 73.4% accuracy. Second, we used MaskRCNN to dynamically segment leaves from backgrounds in combination with GLS_net to identify GLS, resulting in a 72.6% accuracy. Models trained on PlantVillage images were 94.1% accurate at GLS classification with the PlantVillage testing set but performed poorly with the field image dataset (55.1% accuracy). In contrast, the GLS_net model was 78% accurate on the PlantVillage testing set. We conclude that deep learning models trained with realistic mixed disease field data obtain superior degrees of generalizability and external validity when compared to models trained using idealized datasets.The National Research Foundation, South Africa.https://www.mdpi.com/journal/plantsdm2022BiochemistryComputer ScienceForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant PathologyPlant Production and Soil Scienc

Determination of an optimal dose of medetomidine-ketamine-buprenorphine for anaesthesia in the Cape ground squirrel (Xerus inauris)

The optimal dose of medetomidine-ketamine-buprenorphine was determined in 25 Cape ground squirrels (Xerus inauris) undergoing surgical implantation of a temperature logger into the abdominal cavity. At the end of anaesthesia, the squirrels were given atipamezole intramuscularly to reverse the effects of medetomidine. The mean dose of medetomidine was 67.6±9.2 μg/kg, ketamine 13.6±1.9 mg/kg and buprenorphine 0.5±0.06 μg/kg. Induction time was 3.1 ± 1.4 min. This produced surgical anaesthesia for 21± 4.2 min. Atipamezole 232±92 μg/kg produced a rapid recovery. Squirrels were sternally recumbent in 3.5 ± 2.2 min.http://www.journals.co.za/ej/ejour_savet.htm

A One Medicine Mission for an Effective Rabies Therapy

Despite the disease's long history, little progress has been made toward a treatment for rabies. The prognosis for patient recovery remains dire. For any prospect of survival, patients require aggressive critical care, which physicians in rabies endemic areas may be reluctant or unable to provide given the cost, clinical expertise required, and uncertain outcome. Systematic clinical research into combination therapies is further hampered by sporadic occurrence of cases. In this Perspective, we examine the case for a One Medicine approach to accelerate development of an effective therapy for rabies through the veterinary care and investigational treatment of naturally infected dogs in appropriate circumstances. We review the pathogenesis of rabies virus in humans and dogs, including recent advances in our understanding of the molecular basis for the severe neurological dysfunction. We propose that four categories of disease process need to be managed in patients: viral propagation, neuronal degeneration, inflammation and systemic compromise. Compassionate critical care and investigational treatment of naturally infected dogs receiving supportive therapy that mimics the human clinical scenario could increase opportunities to study combination therapies that address these processes, and to identify biomarkers for prognosis and therapeutic response. We discuss the safety and ethics of this approach, and introduce the Canine Rabies Treatment Initiative, a non-profit organization with the mission to apply a One Medicine approach to the investigation of diagnostic, prognostic, and therapeutic options for rabies in naturally infected dogs, to accelerate transformation of rabies into a treatable disease for all patients

The continuum of fetal alcohol spectrum disorders in a community in South Africa: Prevalence and characteristics in a fifth sample

The prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in a fifth sample in a South African community

Antimicrobial susceptibility of gram-negative pathogens isolated from patients with complicated intra-abdominal infections in South African hospitals (SMART Study 2004-2009) : impact of the new carbapenem breakpoints

BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) follows trends in resistance among aerobic and facultative anaerobic gram-negative bacilli (GNB) isolated from complicated intra-abdominal infections (cIAIs) in patients around the world. METHODS: During 2004–2009, three centralized clinical microbiology laboratories serving 59 private hospitals in three large South African cities collected 1,218 GNB from complicated intra-abdominal infections (cIAIs) and tested them for susceptibility to 12 antibiotics according to the 2011 Clinical Laboratory Standards Institute (CLSI) guidelines. RESULTS: Enterobacteriaceae comprised 83.7% of the isolates. Escherichia coli was the species isolated most commonly (46.4%), and 7.6% of these were extended-spectrum b-lactamase (ESBL)-positive. The highest ESBL rate was documented for Klebsiella pneumoniae (41.2%). Overall, ertapenem was the antibiotic most active against susceptible species for which it has breakpoints (94.6%) followed by amikacin (91.9%), piperacillin-tazobactam (89.3%), and imipenem-cilastatin (87.1%), whereas rates of resistance to ceftriaxone, cefotaxime, ciprofloxacin, and levofloxacin were documented to be 29.7%, 28.7%, 22.5%, and 21.1%, respectively. Multi-drug resistance (MDR), defined as resistance to three or more antibiotic classes, was significantly more common in K. pneumoniae (27.9%) than in E. coli (4.9%; p < 0.0001) or Proteus mirabilis (4.1%; p < 0.05). Applying the new CLSI breakpoints for carbapenems, susceptibility to ertapenem was reduced significantly in ESBL-positive E. coli compared with ESBL-negative isolates (91% vs. 98%; p < 0.05), but this did not apply to imipenem-cilastatin (95% vs. 99%; p = 0.0928). A large disparity between imipenem-cilastatin and ertapenem susceptibility in P. mirabilis and Morganella morganii was documented (24% vs. 96% and 15% vs. 92%, respectively), as most isolates of these two species had imipenem-cilastatin minimum inhibitory concentrations in the 2–4 mcg/mL range, which is no longer regarded as susceptible. CONCLUSIONS: This study documented substantial resistance to standard antimicrobial therapy among GNB commonly isolated from cIAIs in South Africa. With the application of the new CLSI carbapenem breakpoints, discrepancies were noted between ertapenem and imipenem-cilastatin with regard to the changes in their individual susceptibilities. Longitudinal surveillance of susceptibility patterns is useful to guide recommendations for empiric antibiotic use in cIAIs.Merck & Co., Inc.http://www.liebertpub.com/overview/surgical-infections/53/am2013ay201