Gyps species have been previously shown to be highly sensitive to the toxic effects of diclofenac, when present in their food sources as drug residues following use as a veterinary medicine. Vultures ...exposed to diclofenac soon become depressed and die with signs of severe visceral gout and renal damage on necropsy. The molecular mechanism behind toxicity and renal excretion of uric acid is still poorly understood. With the clinical pictures suggesting renal uric acid excretion as the target site for toxicity, as a first step the following study was undertaken to determine the uric acid excretory pathways present in the African white-backed vulture (Gyps africanus) (AWB), one of the species susceptible to toxicity. Using transcriptome analysis, immunohistochemistry and functional predictions, we demonstrated that AWB makes use of the organic anion transporter 2 (OAT2) for their uric acid excretion. RT-qPCR analysis subsequently demonstrated relatively similar expression of the OAT2 transporter in the vulture and chicken. Lastly docking analysis, predicted that the non-steroidal drugs induce their toxicity through an allosteric binding.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The following study evaluates the overt toxic potential of carprofen (CRP), flunixin (FXN) and phenylbutazone (PBZ) in Old world vultures in relation to historic toxicity data for diclofenac and ...ketoprofen, with the Cape vulture (Gyps coprotheres) being the indicator species. The toxic potential of a single oral dose of CRP (11.5 mg/kg), FXN (1 mg/kg),PBZ (1.7 mg/kg) or water was evaluated by means of a four-way parallel study (n = 2), as means of ascertaining if these drugs were as toxic as diclofenac in the vulture. No unscheduled deaths or pathological lesions were noted following exposure. Clinical signs of lethargy and depression were, however, noted in one CRP, two FXN and one PBZ treated birds. Mild reversible inhibition of UA excretion was evident in all three groups, although UA remained within the population reference interval in contrast to the effects previously described for diclofenac and ketoprofen. All treatment groups had a drug concentration responsive increase in alanine transferase activity. CRP, FXN and PBZ were characterised by a maximum plasma concentration (Cmax) of 1051.8 ± 620.7 ng/ml, 335.9 ± 36.3 ng/ml and 11150 ± 2474.9 ng/ml at 4 ± 4.3, 0.45 ± 0.02 and 5.3 ± 5.2 hours (Tmax) respectively and a half-life of elimination of 13.3 ±5, 1.8±1 and 18.7 ±11.4 hours respectively. While we could not demonstrate a lethal effect of the tested substances, the presence of toxic clinical signs, clinical pathological changes and/or long half-lives of elimination suggests that all three drugs have a potential for toxicity in a larger population or on repeat administration. In conclusion while the studied substances were not as overtly toxic as diclofenac, they are of safety concern.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diclofenac was responsible for the decimation of Gyps vulture species on the Indian subcontinent during the 1980s and 1990s. Gyps vultures are extremely sensitive (the lethal dose 50 LD50 ~ 0.1 mg/kg ...– 0.2 mg/kg), with toxicity appearing to be linked to metabolic deficiency, demonstrated by the long T1/2 (~12 h – 17 h). This is in striking comparison to the domestic chicken (Gallus gallus domesticus), in which the LD50 is ~10 mg/kg and the T1/2 is ~1 h. The phase 1 cytochrome P450 (CYP) 2C subfamily has been cited as a possible reason for metabolic deficiency. The aim of this study was to determine if CYP2C9 homolog pharmacogenomic differences amongst avian species is driving diclofenac toxicity in Gyps vultures. We exposed each of 10 CYP-inhibited test group chickens to a unique dose of diclofenac (as per the Organisation for Economic Co-operation and Development OECD toxicity testing guidelines) and compared the toxicity and pharmacokinetic results to control group birds that received no CYP inhibitor. Although no differences were noted in the LD50 values for each group (11.92 mg/kg in the CYP-inhibited test group and 11.58 mg/kg in the control group), the pharmacokinetic profile of the test group was suggestive of partial inhibition of CYP metabolism. Evaluation of the metabolite peaks produced also suggested partial metabolic inhibition in test group birds, as they produced lower amounts of metabolites for one of the three peaks demonstrated and had higher diclofenac exposure. This pilot study supports the hypothesis that CYP metabolism is varied amongst bird species and may explain the higher resilience to diclofenac in the chicken versus vultures.
Human and veterinary drug development addresses absorption, distribution, metabolism, elimination and toxicology (ADMET) of the Active Pharmaceutical Ingredient (API) in the target species. ...Metabolism is an important factor in controlling circulating plasma and target tissue API concentrations and in generating metabolites which are more easily eliminated in bile, faeces and urine. The essential purpose of xenobiotic metabolism is to convert lipid-soluble, non-polar and non-excretable chemicals into water soluble, polar molecules that are readily excreted. Xenobiotic metabolism is classified into Phase I enzymatic reactions (which add or expose reactive functional groups on xenobiotic molecules), Phase II reactions (resulting in xenobiotic conjugation with large water-soluble, polar molecules) and Phase III cellular efflux transport processes. The human–fish plasma model provides a useful approach to understanding the pharmacokinetics of APIs (e.g. diclofenac, ibuprofen and propranolol) in freshwater fish, where gill and liver metabolism of APIs have been shown to be of importance. By contrast, wildlife species with low metabolic competency may exhibit zero-order metabolic (pharmacokinetic) profiles and thus high API toxicity, as in the case of diclofenac and the dramatic decline of vulture populations across the Indian subcontinent. A similar threat looms for African Cape Griffon vultures exposed to ketoprofen and meloxicam, recent studies indicating toxicity relates to zero-order metabolism (suggesting P450 Phase I enzyme system or Phase II glucuronidation deficiencies). While all aspects of ADMET are important in toxicity evaluations, these observations demonstrate the importance of methods for predicting API comparative metabolism as a central part of environmental risk assessment.
Oxidative stress negatively affects the welfare of broiler chickens leading to poor productivity and even death. This study examined the negative effect of heat stress on antioxidant enzyme ...activities, small intestinal morphology and performance in broiler chickens administered probiotic and ascorbic acid during the hot summer season, under otherwise controlled conditions. The study made use of 56 broiler chickens; which were divided into control; probiotic (1 g/kg); ascorbic acid (200 mg/kg) and probiotic + ascorbic acid (1 g/kg and 200 mg/kg, respectively). All administrations were given via feed from D1 to D35 of this study. Superoxide dismutase, glutathione peroxidase and catalase activities were highly significant (p < 0.0001) in the treatment groups compared to the control. Performance indicators (water intake and body weight gain) were significantly higher (p < 0.05) in the probiotic and probiotic + ascorbic acid group. The height of duodenal, jejunal and ileal villi, and goblet cell counts of broiler chickens were significantly different in the treatment groups. In conclusion, the study showed that heat stress negatively affects the levels of endogenous antioxidant enzymes, performance and the morphology of small intestinal epithelium, while the antioxidants were efficacious in ameliorating these adverse effects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Vultures in the Gyps genus are declining globally. Multiple threats related to human activity have caused widespread declines of vulture populations in Africa, especially outside protected areas. ...Addressing such threats requires the estimation of foraging ranges yet such estimates are lacking, even for widespread (but declining) species such as the African white-backed vulture (Gyps africanus). We tracked six immature African white-backed vultures in South Africa using GPS-GSM units to study their movement patterns, their use of protected areas and the time they spent in the vicinity of supplementary feeding sites. All individuals foraged widely; their combined foraging ranges extended into six countries in southern Africa (mean (± SE) minimum convex polygon area =269,103±197,187 km(2)) and three of the vultures travelled more than 900 km from the capture site. All six vultures spent the majority of their tracking periods outside protected areas. South African protected areas were very rarely visited whereas protected areas in northern Botswana and Zimbabwe were used more frequently. Two of the vultures visited supplementary feeding sites regularly, with consequent reduced ranging behaviour, suggesting that individuals could alter their foraging behaviour in response to such sites. We show that immature African white-backed vultures are capable of travelling throughout southern Africa, yet use protected areas to only a limited extent, making them susceptible to the full range of threats in the region. The standard approach of designating protected areas to conserve species is unlikely to ensure the protection of such wide-ranging species against threats in the wider landscape.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study investigated the burden and predictors of canine E. coli urinary tract infections (UTI) and antimicrobial resistance among dogs presented at a veterinary teaching hospital in South Africa, ...2007-2012.
The Cochran-Armitage trend test was used to investigate temporal trends while logistic regression models were used to investigate predictors (age, sex, breed, year) of E. coli infections and antimicrobial resistance (AMR).
A total of 22.3% (168/755) of the urinary specimens tested positive for E. coli. A significant (p = 0.0004) decreasing temporal trend in the percentage of E. coli positive isolates was observed over the study period. There were high levels of AMR to penicillin-G (99%), clindamycin (100%), tylosine (95%), cephalothin (84%) but relatively low levels of resistance to enrofloxacin (16%), orbifloxacin (21%). Almost all (98%, 164/167) the isolates exhibited multidrug resistance (MDR), while only 11% (19/167) and 2% (4/167) exhibited extensive drug resistance (XDR) and pan-drug resistance (PDR), respectively.
Although, the risk of E. coli UTI declined during the study period, the risk of AMR increased. The high levels of AMR and MDR as well as the presence of XDR and PDR is concerning as these have the potential of affecting prognosis of UTI treatments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Staphylococcus aureus is internationally recognised as a principal agent of mastitis and the foremost reason for economic loss in the dairy industry. The limited data available on organism-specific ...antibiotic resistance surveillance in dairy cattle have stimulated the need for such a review article. The objective of this study was to review relevant literature on antimicrobial resistance of mastitis-causing staphylococci isolated from dairy cows in South Africa compared to other countries. Factors relating to the incidence of mastitis and treatment strategies in terms of the One Health concept and food security were included. The Web of Science (all databases) and relevant websites were used, and articles not written in English were excluded. The incidence of mastitis varied between South Africa and other countries. Antimicrobial resistance patterns caused by S. aureus also varied in regions within Southern Africa and those of other countries although some similarities were shown. Antimicrobial resistance differed between S. aureus bacteria that were maltose positive and negative (an emerging pathogen). The results highlighted the importance of the availability of organism-specific surveillance data of the incidence of mastitis and antibiotic resistance for specific countries and within similar climatic conditions. Accurate knowledge about whether a specific pathogen is resistant to an antibiotic within a certain climate, country, area or farm should reduce the incidence of unnecessary or incorrect treatment with antibiotics. This should enable dairy farmers to deal with these organisms in a more effective manner. Therefore such research should be ongoing.
In current research guidelines, much focus is placed on ethical management of animals and the application of principles of reduction, refinement and replacement. Of these refinements through ...environmental enrichment is an important aspect when housing primate to prevent behavioural problems. In this study, we investigated the co-housing of domestic cats and vervet monkeys as a novel method of enrichment based on the cohabitation and stress alleviation effect of horses housed with goats and from seeing cats cohabitating with vervet monkeys in an animal sanctuary. The study used a habituation method whereby the cats were stepwise introduced to the monkeys by sight and smell but with physical separation. Assessment included changes in behaviour, weight and faecal glucocorticoid metabolite (fGCM) concentrations over time. On the first day of housing, the vervets whilst inquisitive kept their distance. The vervets housed in cages that were closest to the cats were the most active and during the first minute of introduction made more alarm calls, which stopped a few days later. The fGCMs were non-significantly different. The results of this study provide evidence that vervet monkeys and domestic cats could potentially be housed together without overt aggression. We thus suggest further observations to ascertain if the co-housing could have long-term benefits for vervet monkeys, from the companionship that would be offered by the cats.
Background
Antimicrobial resistance (AMR) is a global health problem largely due to the overuse of antimicrobials. In recognition of this, the World Health Assembly in 2015 agreed on a global action ...plan to tackle AMR. Following the global emergence of the mcr‐1‐associated colistin resistance gene in the livestock industry in 2016, several countries including South Africa restricted the veterinary use of colistin as the gene threatens the clinical utility of the drug. This study is a follow‐up to the restriction in place in order to evaluate the impact of such policy adoption.
Objective
To assess the prevalence of antibacterial resistance (ABR), and the mcr‐1 colistin resistance gene in broiler chicken over a 2‐year period, as a follow‐up to the veterinary ban on colistin use in South Africa.
Methods
A total of 520 swab samples were obtained during 2019 (March–April) and 2020 (February–March), from healthy broiler chicken carcasses (n = 20) and chicken droppings in transport crates (n = 20) at various poultry abattoirs (N = 7) in the Gauteng province of South Africa. Escherichia coli organisms were isolated and subjected to a panel of 24 antibacterials using the MicroScan machine. Screening for mcr‐1 colistin resistance gene was undertaken using PCR.
Result
Four hundred and thirty‐eight (438) E. coli strains were recovered and none demonstrated phenotypic resistance towards colistin, amikacin, carbapenems, tigecycline and piperacillin/tazobactam. The mcr‐1 gene was not detected in any of the isolates tested. Resistances to the aminoglycosides (0%–9.8%) and fluoroquinolones (0%–18.9%) were generally low. Resistances to ampicillin (32%–39.3%) and trimethoprim/sulphamethoxazole (30.6%–3.6%) were fairly high. A significant (p < 0.05) increase in cephalosporins and cephamycin resistance was noted in the year 2020 (February–March) when compared with the year 2019 (March–April).
Conclusion
The absence of mcr‐1 gene and colistin resistance suggests that mitigation strategies adopted were effective and clearly demonstrated the significance of regulatory interventions in reducing resistance to critical drugs. Despite the drawback in regulatory framework such as free farmers access to antimicrobials OTC and a dual registration system in place, there is a general decline in the prevalence of ABR when the present data are compared with the last national veterinary surveillance on AMR (SANVAD 2007). To further drive resistance down, mitigation strategies should focus on strengthening regulatory framework, the withdrawal of OTC dispensing of antimicrobials, capping volumes of antimicrobials, banning growth promoters and investing on routine surveillance/monitoring of AMR and antimicrobial consumption.
Following the emergence of the mcr‐1‐associated colistin resistance gene in the poultry industry of South Africa, the veterinary use of colistin was restricted by government to mitigate spread. The present study evaluated the impact of this government policy and demonstrated a general decline in the incidence of the mcr‐1 gene, and colistin resistance following the regulatory intervention.
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