Browsing by Author "Singh P"

Now showing 1 - 8 of 8
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    Coastal development and precipitation drive pathogen flow from land to sea: evidence from a Toxoplasma gondii and felid host system.
    (26/07/2016) VanWormer E; Carpenter TE; Singh P; Shapiro K; Wallender WW; Conrad PA; Largier JL; Maneta MP; Mazet JAK
    Rapidly developing coastal regions face consequences of land use and climate change including flooding and increased sediment, nutrient, and chemical runoff, but these forces may also enhance pathogen runoff, which threatens human, animal, and ecosystem health. Using the zoonotic parasite Toxoplasma gondii in California, USA as a model for coastal pathogen pollution, we examine the spatial distribution of parasite runoff and the impacts of precipitation and development on projected pathogen delivery to the ocean. Oocysts, the extremely hardy free-living environmental stage of T. gondii shed in faeces of domestic and wild felids, are carried to the ocean by freshwater runoff. Linking spatial pathogen loading and transport models, we show that watersheds with the highest levels of oocyst runoff align closely with regions of increased sentinel marine mammal T. gondii infection. These watersheds are characterized by higher levels of coastal development and larger domestic cat populations. Increases in coastal development and precipitation independently raised oocyst delivery to the ocean (average increases of 44% and 79%, respectively), but dramatically increased parasite runoff when combined (175% average increase). Anthropogenic changes in landscapes and climate can accelerate runoff of diverse pathogens from terrestrial to aquatic environments, influencing transmission to people, domestic animals, and wildlife.
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    Comparison of electroencephalographic changes in response to acute electrical and thermal stimuli with the tail flick and hot plate test in rats administered with opiorphin
    (BioMed Central Ltd, 19/04/2018) Singh P; Kongara K; Harding D; Ward N; Dukkipati VSR; Johnson C; Chambers P
    Background The objective of this study was to compare the changes in the electroencephalogram (EEG) in response to noxious stimuli with tail flick and hot plate responses of rats administered opiorphin. Methods Female Sprague -Dawley rats (n = 8 per group) randomly received intravenous (IV) injection of morphine (1 mg/kg,) or opiorphin (2 mg/kg,) or saline (0.5 ml,) in each of the three testing methods (EEG, tail flick and hot plate). Each type of test (n = 24 per test) was conducted in different population of rats on separate occasions. The tail flick and hot plate latencies were recorded until 5 min after test drug administration to conscious rats. The EEG was recorded in anaesthetised rats subjected to noxious thermal and electrical stimuli after test drug administration. At the end of 5 min in each of the testing methods rats were administered naloxone subcutaneously (SC) (1 mg/kg) and the test procedure was repeated. Results There was no significant increase in the median frequency and spectral edge frequency (F50 & F95) of EEG, indicators of nociception, of morphine and opiorphin groups after noxious stimulation. Noxious stimuli caused a significant increase in both F50 and F95 of the saline group. An injection of naloxone significantly increased the F50, thus blocking the action of both opiorphin and morphine. There was a significant increase in the tail flick latency after administration of opiorphin and morphine as compared to the baseline values. Rats of morphine group spent significantly longer on the hot plate when compared to those of the opiorphin and saline groups. There was no significant difference in the hot plate latencies of opiorphin and saline groups. Conclusion The results of this study suggest that the analgesic effect of opiorphin occurs at the spinal level and it is not as effective as morphine at supraspinal level. It may be due to rapid degradation of opiorphin or limited ability of opiorphin to cross the blood brain barrier or a higher dose of opiorphin is required for its action in the brain. Pharmacokinetic/pharmacodynamics studies along with in vivo penetration of opiorphin in the cerebrospinal fluid are required for further evaluation of opiorphin analgesia.
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    Pain Assessment in Goat Kids: Focus on Disbudding
    (MDPI AG, Basel, Switzerland, 2023-12-11) Kongara K; Singh P; Venkatachalam D; Chambers JP
    Farm animals are routinely subjected to painful husbandry procedures for various purposes. Goat kids are disbudded to improve goat welfare and to ensure safety of other livestock, farm personnel, attending veterinarians and for various other production and managemental procedures. Disbudding is commonly performed on dairy goat farms, in kids under 3 weeks of age. Many scientific studies reported physiological and behavioural changes indicating pain and distress following disbudding, and this can be a significant cause of welfare compromise in goat kids. Recognition and measurement of pain is important to treat and/or manage pain and distress following painful procedures. This review focuses on pain assessment in goat kids following disbudding, using both physiological and behavioural measures. As only a limited information is available on the topic of interest, relevant studies in other young farm animals have also been discussed to compare the status quo in goat kids.
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    Pain Mitigation Strategies for Disbudding in Goat Kids
    (MDPI (Basel, Switzerland), 2024-02-07) Singh P; Venkatachalam D; Kongara K; Chambers P; Oliver M
    Pain mitigation strategies for disbudding in goat kids have gained significant attention in recent years because of growing concerns for animal welfare. Disbudding, the removal of horn buds in young goats, is a common practice to enhance safety and manage herd dynamics. However, the procedure will cause pain and distress if not managed effectively. This review covers the array of pain mitigation techniques currently available for disbudding, including the efficacy of these strategies in reducing pain and stress during the disbudding process, with specific attention to the potential toxicity associated with local anesthetics. The current best practice for disbudding on the farm suggests sedation/analgesia with an alpha-2 agonist, the placement of a two-point cornual nerve block, and then an NSAID for postoperative pain. In conclusion, this review offers recommendations for future research directions aimed at enhancing the welfare of young goats subjected to the disbudding procedure. These suggestions hold the promise of fostering significant improvements in the overall well-being of these animals.
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    Pharmacokinetics and efficacy of a novel long-acting bupivacaine formulation for cornual nerve block in calves
    (Frontiers Media S.A., 2022-12-01) Venkatachalam D; Kells N; Chambers P; Jacob A; Ward N; Singh P; Soto-Blanco B
    Local anesthetics are commonly used in farm animals to provide analgesia for painful procedures but can cause adverse effects at high systemic concentrations. The pharmacokinetics and efficacy of a long-acting sucrose acetate isobutyrate (SAIB) bupivacaine formulation following cornual nerve block in calves were compared to lidocaine. Fourteen calves were randomly assigned to one of the treatment groups (i) 5% Bupivacaine-SAIB (BUP-SAIB), n = 7; or (ii) 2% lidocaine (LID), n = 7. Cornual nerve block was performed, and duration of effective analgesia was evaluated by nociceptive threshold testing using a hand-held pressure algometer. Blood samples were collected at various time points and plasma concentrations were analyzed by HPLC. Pharmacokinetic parameters were calculated using a non-compartmental model. The mechanical nociceptive thresholds showed that the novel formulation could desensitize the skin around the horn bud for 18.77 ± 8.88 h (range 8-36 h), compared to 0.79 ± 0.34 h (range 0.5-1.5 h) with lidocaine. The mean maximum plasma concentration (Cmax) of bupivacaine was 152.03 (SD 37.34) ng/mL and its Tmax was 0.39 (SD 0.13) h. The half-life of elimination was 32.79 ± 11.00 h and the rate of clearance was 0.12 ± 0.03 L h-1. No toxicity signs were seen after treatment in either group. The novel formulation produced long-lasting analgesia of several times greater duration than that produced by lidocaine. This study showed that the safety and efficacy of the SAIB formulation justifies further studies in a larger population of animals.
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    Pharmacokinetics and Pharmacodynamics of Butorphanol and Dexmedetomidine after Intranasal Administration in Broiler Chickens (Gallus gallus domesticus)
    (MDPI (Basel, Switzerland), 2022-04-25) Sha J; Kongara K; Singh P; Jacob A; Ponnampalam J; Guedes A
    Butorphanol and dexmedetomidine (DXM) can produce analgesia in birds. Intranasal (IN) route of drug administration is easier, and free of risks such as pain and tissue damage compared with intravenous, intramuscular or subcutaneous routes in bird species, including wild birds. Although previous studies have demonstrated the use of IN route for producing sedation, no studies are available on the pharmacokinetics and pharmacodynamics of IN drugs in birds. This study analyzed the pharmacokinetics and sedative–analgesic efficacy of intranasal butorphanol (2 mg/kg), dexmedetomidine (80 µg/kg) and their combination (butorphanol, 2 mg/kg; DXM, 80 µg/kg) in healthy, male, Ross broiler chickens (n = 6/group) aged between 6 and 8 weeks. Maximum plasma concentration (Cmax, p = 0.01), area under the plasma concentration-time curve from time zero to 120 min (AUC0 to 120, p = 0.02) and apparent volume of distribution at steady state (Vss, p = 0.02) of DXM were significantly higher than that of DXM co-administered with butorphanol. The mechanical nociceptive thresholds and the sedation scores of DXM group were significantly higher than the baseline value. Dexmedetomidine (80 µg/kg, IN) was effective in chickens, and the drug absorption was more rapid than that of DXM with butorphanol. However, the duration of action of DXM was short. Lower value of Cmax and nociceptive thresholds showed the nonsignificant efficacy of butorphanol at a dose of 2 mg/kg after IN administration in broiler chickens.
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    Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid after subcutaneous administration in red deer (Cervus elaphus)
    (Taylor & Francis, 23/10/2017) Venkatachalam D; Chambers JP; Kongara K; Singh P
    AIM: To develop and validate a simple and sensitive method using liquid chromatography-mass spectrometry (LC-MS) for quantification of articaine, and its major metabolite articainic acid, in plasma of red deer (Cervus elaphus), and to investigate the pharmacokinetics of articaine hydrochloride and articainic acid in red deer following S/C administration of articaine hydrochloride as a complete ring block around the antler pedicle. METHODS: The LC-MS method was validated by determining linearity, sensitivity, recovery, carry-over and repeatability. Articaine hydrochloride (40 mg/mL) was administered S/C to six healthy male red deer, at a dose of 1 mL/cm of pedicle circumference, as a complete ring block around the base of each antler. Blood samples were collected at various times over the following 12 hours. Concentrations in plasma of articaine and articainic acid were quantified using the validated LC-MS method. Pharmacokinetic parameters of articaine and articainic acid were estimated using non-compartmental analysis. RESULTS: Calibration curves were linear for both articaine and articainic acid. The limits of quantifications for articaine and articainic acid were 5 and 10 ng/mL, respectively. Extraction recoveries were >72% for articaine and >68% for articainic acid. After S/C administration as a ring block around the base of each antler, mean maximum concentrations in plasma (Cmax) of articaine were 1,013.9 (SD 510.1) ng/mL, detected at 0.17 (SD 0.00) hours, and the Cmax for articainic acid was 762.6 (SD 95.4) ng/mL at 0.50 (SD 0.00) hours. The elimination half-lives of articaine hydrochloride and articainic acid were 1.12 (SD 0.17) and 0.90 (SD 0.07) hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The LC-MS method used for the quantification of articaine and its metabolite articainic acid in the plasma of red deer was simple, accurate and sensitive. Articaine hydrochloride was rapidly absorbed, hydrolysed to its inactive metabolite articainic acid, and eliminated following S/C administration as a ring block in red deer. These favourable pharmacokinetic properties suggest that articaine hydrochloride should be tested for efficacy as a local anaesthetic in red deer for removal of velvet antlers. Further studies to evaluate the safety and residues of articaine hydrochloride and articainic acid are required before articaine can be recommended for use as a local anaesthetic for this purpose.
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    Toxicity and pharmacokinetic studies of lidocaine and its active metabolite, monoethylglycinexylidide, in goat kids
    (MDPI, 2018-08) Venkatachalam D; Chambers P; Kongara K; Singh P
    This study determined the convulsant plasma concentrations and pharmacokinetic parameters following cornual nerve block and compared the results to recommend a safe dose of lidocaine hydrochloride for goat kids. The plasma concentrations of lidocaine and monoethylglycinexylidide (MGX) were quantified using liquid chromatography-mass spectrometry. A total dose of 7 mg/kg body weight (BW) was tolerated and should therefore be safe for local and regional anesthesia in goat kids. The mean plasma concentration and mean total dose that produced convulsions in goat kids were 13.59 ± 2.34 µg/mL and 12.31 ± 1.42 mg/kg BW (mean ± S.D.), respectively. The absorption of lidocaine following subcutaneous administration was rapid with Cmax and Tmax of 2.12 ± 0.81 µg/mL and 0.33 ± 0.11 h, respectively. The elimination half-lives (t½λz) of lidocaine hydrochloride and MGX were 1.71 ± 0.51 h and 3.19 ± 1.21 h, respectively. Injection of 1% lidocaine hydrochloride (0.5 mL/site) was safe and effective in blocking the nerves supplying horn buds in goat kids.