Carprofen Attenuates Postoperative Mechanical and Thermal Hypersensitivity after Plantar Incision in Immunodeficient NSG Mice.

Immunodeficient NSG mice are reported to be less responsive to buprenorphine analgesia. Here, we used NSG mice to compare the efficacy of the commonly used dose of carprofen (5 mg/kg) with 5 and 10 times that dose (25 and 50 mg/kg) for attenuating postoperative mechanical and thermal hypersensitivity following an incisional pain model. Male and female NSG mice (n = 45) were randomly assigned to one of 4 groups and received daily subcutaneous injections for 3 d: saline (5 mL/kg), 5 mg/kg carprofen (Carp5), 25 mg/kg carprofen (Carp25), and 50 mg/kg carprofen (Carp50). Mechanical and thermal hypersensitivity were assessed 24 h before and at 4, 24, and 48 h after surgery. Plasma carprofen concentrations were measured in a separate group of mice (n = 56) on days 0 (at 2, 4, 12, and 23 h), 1, and 2 after the first, second, and third doses, respectively. Toxicity was assessed through daily fecal occult blood testing (n = 27) as well as gross and histopathologic evaluation (n = 15). Our results indicated that the saline group showed both mechanical and thermal hypersensitivity throughout the study. Carp5 did not attenuate mechanical or thermal hypersensitivity at any time point. Carp25 attenuated mechanical and thermal (except for the 4-h time point) hypersensitivity. Carp50 attenuated only thermal hypersensitivity at 24 h. Fecal occult blood was detected in 1 of 8 Carp25-treated mice at 48 and 72 h. Histopathologic abnormalities (gastric ulceration, ulcerative enteritis, and renal lesions) were observed in some Carp50-treated mice. Plasma carprofen concentrations were dose and time dependent. Our results indicate that Carp25 attenuated postoperative mechanical and thermal hypersensitivity more effectively than Carp5 or Carp50 in NSG mice with incisional pain. Therefore, we recommend providing carprofen at 25 mg/kg SID for incisional pain procedures using immunodeficient NSG mouse.

Comparing Three Formulations of Buprenorphine in an Incisional Pain Model in Mice.

This study compared the therapeutic effects in mice of 3 different formulations of buprenorphine. These formulations were standard buprenorphine hydrochloride (Bup-HCL) and 2 different extended-release buprenorphine formulations (Bup-ER and Ethiqa-XR [Bup-XR]). Drugs were evaluated based on their ability to attenuate thermal hypersensitivity in a mouse plantar incisional pain model. We hypothesized that Bup-HCL would attenuate postoperative thermal hypersensitivity at 20 min after administration, and that Bup-ER and Bup-XR would attenuate thermal hypersensitivity at 40 min after administration. Male C57BL6/J mice were randomly assigned to 1 of 4 treatment groups: 1) saline, 5 mL/kg SC, once; 2) Bup-HCL, 0.1 mg/kg SC, once; 3) Bup-ER, 1 mg/kg, SC, once; and 4) Bup-XR, 3.25 mg/kg, SC, once. Thermal hypersensitivity was assessed on the day before surgery and again on the day of surgery at 20, 40, 60, 90, and 120 min after drug administration. Thermal hypersensitivity after surgery was not different among the Bup-HCL, Bup-ER and Bup-XR groups at any timepoint. In addition, all buprenorphine treatment groups showed significantly less thermal hypersensitivity after surgery than did the saline group. Subjective observations suggested that mice that received Bup-ER or Bup-XR became hyperactive after drug administration (83 and 75% of mice tested, respectively). Our results indicate that Bup-HCL, Bup-ER, or Bup-XR attenuate thermal hyper- sensitivity related to foot incision by 20 min after administration.

Forecasting of daily new lumpy skin disease cases in Thailand at different stages of the epidemic using fuzzy logic time series, NNAR, and ARIMA methods.

Lumpy skin disease (LSD) is an important transboundary disease affecting cattle in numerous countries in various continents. In Thailand, LSD is regarded as a serious threat to the cattle industry. Disease forecasting can assist authorities in formulating prevention and control policies. Therefore, the objective of this study was to compare the performance of time series models in forecasting a potential LSD epidemic in Thailand using nationwide data. For the forecasting of daily new cases, fuzzy time series (FTS), neural network auto-regressive (NNAR), and auto-regressive integrated moving average (ARIMA) models were applied to various datasets representing the different stages of the epidemic. Non-overlapping sliding and expanding window approaches were also employed to train the forecasting models. The results showed that the FTS outperformed other models in five of the seven validation datasets based on various error metrics. The predictive performance of the NNAR and ARIMA models was comparable, with NNAR outperforming ARIMA in some datasets and vice versa. Furthermore, the performance of models built from sliding and expanding window techniques was different. This is the first study to compare the forecasting abilities of the FTS, NNAR, and ARIMA models across multiple phases of the LSD epidemic. Livestock authorities and decision-makers may incorporate the forecasting techniques demonstrated herein into the LSD surveillance system to enhance its functionality and utility.

Essential genetic modifiers and their measurable impact in a community-recruited population analysis for non-severe hemoglobin E/ß-thalassemia prenatal genetic counseling.

The study aimed to identify essential phenotype-modulating factors among the pre-existence of several important ones and clarify their measurable impact on the clinical severity of hemoglobin (Hb) E/ß-thalassemia in a community-recruited population analysis. This prospective study was designed to compare modifiers between community- (less or no symptoms) and hospital-recruited individuals with Hb E/ß-thalassemia. The formerly included couples previously assessed for prenatal thalassemia at-risk status at 42 community and 7 referral hospitals in Thailand through on-site investigations between June 2020 and December 2021. The control included Hb E/ß-thalassemia patients undergoing transfusions. The Mahidol score classified disease severity. Beta-globin, α0-thalassemia (-SEA, -THAI), α+-thalassemia (-α3.7, -α4.2), Hb Constant Spring (αCS) alleles, rs766432 in BCL11A, rs9399137 in HBS1L-MYB, and rs7482144-XmnI were evaluated. Modifiers were compared between 102 community- and 104 hospital-recruited cases. Alleles of ß+, -SEA, -α3.7, αCS, and a minor allele of rs9399137 were prevalent in the community and mild severity groups (p < 0.05). Multiple linear regression analysis associated modulating alleles with -4.299 (-SEA), -3.654 (ß+), -3.065 (rs9399137, C/C), -2.888 (αCS), -2.623 (-α3.7), -2.361 (rs7482144, A/A), -1.258 (rs9399137, C/T), and -1.174 (rs7482144, A/G) severity score reductions (p < 0.05). Certain modifiers must be considered in routine prenatal genetic counseling for Hb E/ß-thalassemia.

Efficacy of Supplemental Diet Gels for Preventing Postoperative Weight Loss in Mice ( Mus musculus).

This study investigated whether the use of commercially available diet gels prevented the postoperative weight loss associated with major survival surgery in mice. C57BL/6 mice were divided into 3 groups ( n = 9 per group) that received moistened chow pellets alone or with one of 2 commercially available diet gels. Mice began receiving the test diets 3 d before surgery (baseline) and were weighed daily for 7 d after surgery. On day 0, mice underwent ventral midline laparotomy, during which the intestines were manipulated for 2 min and a segment of jejunum was briefly clamped. Compared with the baseline value for the same group, body weights for the mice that received moistened chow only were significantly lower on all postoperative days (days 1 through 7). In contrast, body weights of mice that received both moistened chow and diet gel differed from baseline only on days 2 and 3 for one product and were never different from baseline for the other product. This study indicates that the combination of diet gel and moistened chow prevented or mitigated postoperative weight loss after a laparotomy procedure in mice.

The impact of mass vaccination policy and control measures on lumpy skin disease cases in Thailand: insights from a Bayesian structural time series analysis.

Introduction: In 2021, Thailand reported the highest incidence of lumpy skin disease (LSD) outbreaks in Asia. In response to the widespread outbreaks in cattle herds, the government's livestock authorities initiated comprehensive intervention measures, encompassing control strategies and a national vaccination program. Yet, the efficacy of these interventions remained unevaluated. This research sought to assess the nationwide intervention's impact on the incidence of new LSD cases through causal impact analysis. Methods: Data on weekly new LSD cases in Thailand from March to September 2021 was analyzed. The Bayesian structural time series (BSTS) analysis was employed to evaluate the causal relationship between new LSD cases in the pre-intervention phase (prior to the vaccination campaign) and the post-intervention phase (following the vaccination campaign). The assessment involved two distinct scenarios, each determined by the estimated effective intervention dates. In both scenarios, a consistent decline in new LSD cases was observed after the mass vaccination initiative, while other control measures such as the restriction of animal movement, insect control, and the enhancement of the active surveillance approach remained operational throughout the pre-intervention and the post-intervention phases. Results and discussion: According to the relative effect results obtained from scenario A and B, it was observed that the incidence of LSD cases exhibited reductions of 119% (95% Credible interval [CrI]: -121%, -38%) and 78% (95% CrI: -126, -41%), respectively. The BSTS results underscored the significant influence of these interventions, with a Bayesian one-sided tail-area probability of p < 0.05. This model-based study provides insight into the application of BSTS in evaluating the impact of nationwide LSD vaccination based on the national-level data. The present study is groundbreaking in two respects: it is the first study to quantify the causal effects of a mass vaccination intervention on the LSD outbreak in Thailand, and it stands as the only endeavor of its kind in the Asian context. The insights collected from this study hold potential value for policymakers in Thailand and other countries at risk of LSD outbreaks.

Bupivacaine as a euthanasia agent for African Clawed Frogs (Xenopus laevis).

Immersion in tricaine methanesulfonate (i.e. TMS) has been used for euthanasia of Xenopus laevis (African Clawed frogs). However, the time for preparation and potential human health hazards may pose as a barrier for large group culls. Here, we aimed to investigate whether immersion in bupivacaine is an effective means to euthanize this species. In experiment one, frogs (n = 10/group) were randomly assigned to 1-h immersion in 1 of 3 treatment groups: 1) TMS-5 (MS-222, 5g/L); 2) TMS-10 (MS-222, 10 g/L); or 3) Bupi-1.5 (0.5% Bupivacaine, 1.5 g/L). Frogs were then removed from solutions, rinsed with system water, and placed into a recovery cage. Heart rate was evaluated audibly via doppler ultrasound flow over 1 min at immediate removal (T1h), at 2 (T2h), and 3 (T3h) h in the recovery cage. In experiment two, frogs (n = 7/group) underwent 5-h & 19-h immersion in either TMS-5 or Bupi-1.5, with heart rate assessment at 5 and 19 hrs. Righting reflex and withdrawal reflex of the hindlimb were tested during the experiments. Experiment one-after the 1-h immersion, Bupi-1.5 treated animals had decreased heart rates compared to TMS-5 and TMS-10 treated animals by T2h. Neither TMS-5, TMS-10, nor Bupi-1.5 ceased heart rate after the 1-h immersion. Experiment two-after the 5-h immersion, Bupi-1.5 and TMS-5 treated animals were comparable in heart rates. 43% of TMS-5 animals and 14% of the Bupi-1.5 animals had completely ceased heart rates at T5h. At 19 h all remaining animals exhibited rigor mortis and had ceased heart rate. We recommend 19-h of immersion using either TMS-5 or Bupi-1.5 for cessation of heart rate in African Clawed frogs. These data are strong support for the use of secondary physical methods for euthanasia in African Clawed frogs when euthanasia by immersion is performed.

Effectiveness of two extended-release buprenorphine formulations during postoperative period in neonatal rats.

Information on the effectiveness of a new long-lasting buprenorphine formulation, extended-release buprenorphine, in the neonatal rat is very limited. This study compares whether a high dose of extended-release buprenorphine (XR-Hi) attenuates thermal hypersensitivity for a longer period than a low dose of extended-release buprenorphine (XR-Lo) in a neonatal rat incisional pain model. Two experiments were performed. Experiment one: Male and female postnatal day-5 rat pups (n = 38) were randomly assigned to 1 of 4 treatment groups and received a subcutaneous administration of one of the following: 1) 0.9%NaCl (Saline), 0.1 mL; 2) sustained release buprenorphine (Bup-SR), 1 mg/kg; 3) XR-Lo, 0.65 mg/kg; and 4) XR-Hi, 1.3 mg/kg. Pups were anesthetized with sevoflurane in 100% O2 and a 5 mm long skin incision was made over the left lateral thigh and underlying muscle dissected. The skin was closed with surgical tissue glue. Thermal hypersensitivity testing (using a laser diode) and clinical observations were conducted 1 hour (h) prior to surgery and subsequently after 1, 4, 8, 24, 48, 72 h of treatment. Experiment two: The plasma buprenorphine concentration level was evaluated at 1, 4, 8, 24, 48, 72 h on five-day-old rat pups. Plasma buprenorphine concentration for all treatment groups remained above the clinically effective concentration of 1 ng/mL for at least 4 h in the Bup-SR group, 8 h in XR-Lo and 24 h in XR-Hi group with no abnormal clinical observations. This study demonstrates that XR-Hi did not attenuate postoperative thermal hypersensitivity for a longer period than XR-Lo in 5-day-old rats; XR-Hi attenuated postoperative thermal hypersensitivity for up to 4 h while Bup-SR and XR-Lo for at least 8 h in this model.

Use of Ketamine or Xylazine to Provide Balanced Anesthesia with Isoflurane in C57BL/6J Mice.

Balanced anesthesia-the use of a combination of drugs to achieve a desired anesthetic plane-offers many benefits, including smoother induction and recovery and fewer adverse effects than occur with individual drugs. Although premedication prior to inhalant anesthesia is routine in other species, mice are commonly induced with gas anesthesia alone. The hypothesis of this study was that premedication with ketamine or xylazine would safely reduce the stress of isoflurane induction and lower the minimum alveolar concentration (MAC) of isoflurane. Young adult male and female C57BL/6J mice were premedicated with ketamine (100 mg/kg), xylazine (4 mg/kg), or isotonic crystalloid (0.1 mL) and were used in 4 experiments. First, isoflurane induction was video recorded under all test conditions, and the videos were scored according to a behavioral ethogram to identify signs of distress. Mice in the ketamine group experienced tremors and ataxia before and dur- ing induction. Therefore, ketamine was given after induction with isoflurane in subsequent experiments. Second, the MAC value for each anesthetic protocol was determined by using quantal and bracketing analysis. Third, mice were anesthetized according to the 3 protocols, and vital parameters were monitored for 60 min. Finally, anesthetized mice were challenged with hypoxia and hypovolemia, and vital parameters were monitored. Premedication with xylazine significantly reduced the stress scores for isoflurane induction (control, 7.3 ± 1.5; ketamine, 6.0 ± 3.0; xylazine, 3.1 ± 1.0). Ketamine and xylazine both reduced the MAC of isoflurane (control, 1.89%; ketamine, 0.96%; xylazine, 1.20%). All mice survived 60 min of anesthesia and the hypoxia-hypovolemia challenge. Premedication with xylazine reduced the stress of induction and lowered the necessary dose of isoflurane in C57BL/6J mice to maintain a surgical plane of anesthesia. We recommend administering xylazine before isoflurane induction and anesthesia of healthy mice that are undergoing procedures in which 100% oxygen is provided and anticipated blood loss is less than 10% to 15% of the total blood volume.

Time-Series Analysis for the Number of Foot and Mouth Disease Outbreak Episodes in Cattle Farms in Thailand Using Data from 2010-2020.

Thailand is one of the countries where foot and mouth disease outbreaks have resulted in considerable economic losses. Forecasting is an important warning technique that can allow authorities to establish an FMD surveillance and control program. This study aimed to model and forecast the monthly number of FMD outbreak episodes (n-FMD episodes) in Thailand using the time-series methods, including seasonal autoregressive integrated moving average (SARIMA), error trend seasonality (ETS), neural network autoregression (NNAR), and Trigonometric Exponential smoothing state−space model with Box−Cox transformation, ARMA errors, Trend and Seasonal components (TBATS), and hybrid methods. These methods were applied to monthly n-FMD episodes (n = 1209) from January 2010 to December 2020. Results showed that the n-FMD episodes had a stable trend from 2010 to 2020, but they appeared to increase from 2014 to 2020. The outbreak episodes followed a seasonal pattern, with a predominant peak occurring from September to November annually. The single-technique methods yielded the best-fitting time-series models, including SARIMA(1,0,1)(0,1,1)12, NNAR(3,1,2)12,ETS(A,N,A), and TBATS(1,{0,0},0.8,{<12,5>}. Moreover, SARIMA-NNAR and NNAR-TBATS were the hybrid models that performed the best on the validation datasets. The models that incorporate seasonality and a non-linear trend performed better than others. The forecasts highlighted the rising trend of n-FMD episodes in Thailand, which shares borders with several FMD endemic countries in which cross-border trading of cattle is found common. Thus, control strategies and effective measures to prevent FMD outbreaks should be strengthened not only in Thailand but also in neighboring countries.

First study on assessments of farmers' benefits under a payment program based on dairy milk quality in Thailand.

Background and Aim: To improve overall milk quality in Thailand, dairy farmers and milk collection centers employ a payment program based on milk quality (PPBMQ) for milk trade. This study aimed to determine and compare the proportion of dairy farmers receiving benefits from the PPBMQ using data from selected dairy cooperatives located in northern and central regions in Thailand. Materials and Methods: Monthly data on milk components (n=37,077), including fat, solids not fat (SNF), and somatic cell counts (SCC) were collected from the two regions in 2018 and 2019. Based on the PPBMQ, farmers were classified into benefit-gain, benefit-loss, and no-benefit groups. A mixed-effects logistic regression model was used to compare the number of farmers in northern and central regions who received monthly benefits from the PPBMQ. Results: More than 70% of dairy farmers benefited from the PPBMQ. The proportion of dairy farmers in the benefit-gain group was higher in the northern region (88.7%) than in the central region (57.1%). A high percentage of dairy farmers in the central region lost their benefits mainly due to SCC (40%) and SNF (44%). Conclusion: The PPBMQ benefited the vast majority of dairy producers in the northern region and approximately two-thirds of those in the central region. Thus, the efforts of authorities and stakeholders should be enhanced to support dairy farmers in the central region in improving milk quality.

Extended-release Buprenorphine, an FDAindexed Analgesic, Attenuates Mechanical Hypersensitivity in Rats (Rattus norvegicus).

A new extended-release buprenorphine (XR), an FDA-indexed analgesic, has recently become available to the laboratory animal community. However, the effectiveness and dosing of XR has not been extensively evaluated for rats. We investigated XR's effectiveness in attenuating postoperative hypersensitivity in a rat incisional pain model. We hypothesized that high dose of XR would attenuate mechanical and thermal hypersensitivity more effectively than the low dose of XR in this model. We performed 2 experiments. In experiment 1, male adult Sprague-Dawley rats (n = 31) were randomly assigned to 1 of the 4 treatment groups: 1) saline (saline, 0.9% NaCl, 5 mL/kg, SC, once); 2) sustained-release buprenorphine (Bup-SR; 1.2 mg/kg, SC, once), 3) low-dose extended-release buprenorphine (XR-Lo; 0.65 mg/kg, SC, once), and 4) high-dose extended-release buprenorphine (XR-Hi; 1.3 mg/kg, SC, once). After drug administration, a 1 cm skin incision was made on the plantar hind paw under anesthesia. Mechanical and thermal hypersensitivity were evaluated 1 d before surgery (D-1), 4 h after surgery (D0), and for 3 d after surgery (D1, D2, and D3). In experiment 2, plasma buprenorphine concentration (n = 39) was measured at D0, D1, D2, and D3. Clinical observations were recorded daily, and a gross necropsy was performed on D3. Mechanical and thermal hypersensitivity were measured for 3 d (D0-D3) in the saline group. Bup-SR, XR-Lo, and XR-Hi effectively attenuated mechanical hypersensitivity for D0-D3. Plasma buprenorphine concentrations remained above 1 ng/mL on D0 and D1 in all treatment groups. No abnormal clinical signs were noted, but injection site reactions were evident in the Bup-SR (71%), XR-Lo (75%), and XR-Hi (87%) groups. This study indicates that XR-Hi did not attenuate hypersensitivity more effectively than did XR-Lo in this model. XR 0.65 mg/kg is recommended to attenuate postoperative mechanical hypersensitivity for up to 72 h in rats in an incisional pain model.

Forecasting of Milk Production in Northern Thailand Using Seasonal Autoregressive Integrated Moving Average, Error Trend Seasonality, and Hybrid Models.

Milk production in Thailand has increased rapidly, though excess milk supply is one of the major concerns. Forecasting can reveal the important information that can support authorities and stakeholders to establish a plan to compromise the oversupply of milk. The aim of this study was to forecast milk production in the northern region of Thailand using time-series forecast methods. A single-technique model, including seasonal autoregressive integrated moving average (SARIMA) and error trend seasonality (ETS), and a hybrid model of SARIMA-ETS were applied to milk production data to develop forecast models. The performance of the models developed was compared using several error matrices. Results showed that milk production was forecasted to raise by 3.2 to 3.6% annually. The SARIMA-ETS hybrid model had the highest forecast performances compared with other models, and the ETS outperformed the SARIMA in predictive ability. Furthermore, the forecast models highlighted a continuously increasing trend with evidence of a seasonal fluctuation for future milk production. The results from this study emphasizes the need for an effective plan and strategy to manage milk production to alleviate a possible oversupply. Policymakers and stakeholders can use our forecasts to develop short- and long-term strategies for managing milk production.

Efficacy of an Anti-Cellulite Herbal Emgel: A Randomized Clinical Trial.

Cellulite describes unsightly skin overlying subcutaneous fat around thighs and buttocks of post-pubescent females. A herbal 'emgel' containing volatile oils and extracts of A traditional Thai herbal compress was tested in a double-blind, placebo-controlled trial with 18 women aged 20-50 year with severe cellulite. Appearance of cellulite (primary outcome), thigh circumferences, skin firmness, and cutaneous blood flow (secondary outcomes) were assessed at baseline, 2, 4, 8 and 12 weeks with a 2-week follow-up. Herbal emgel applied onto the thigh skin twice daily reduced cellulite severity scores in every time point. The score was reduced from 13.4 ± 0.3 (baseline) to 12.1 ± 0.3 (week 2) and 9.9 ± 0.6 (week 12). All secondary outcomes improved with both placebo and herbal emgels suggesting that ingredients in the base-formulation might be responsible. Querying of participants, analysis of their diaries, and physical monthly inspections found no adverse events. The herbal emgel safely improved the appearance of cellulite, while the base emgel may play a role for other endpoints. Further studies on the active constituents and their mechanism of action are needed to further explore these factors.

Lipid bound extended release buprenorphine (high and low doses) and sustained release buprenorphine effectively attenuate post-operative hypersensitivity in an incisional pain model in mice (Mus musculus).

Background: Extended-release buprenorphine (XR) is indicated for pain management in rodents, but little is known about its use in mice. This study aimed to investigate whether high dose XR effectively attenuates post-operative hypersensitivity better than low dose XR in a mouse model of incisional pain. Methods: Mice (n = 44) were randomly assigned to 1 of 4 treatment groups: (a) saline (1 ml/kg SC, once); (b) sustained release buprenorphine (Bup-SR, 1 mg/kg SC, once); (c) low dose extended-release buprenorphine (XR-lo, 3.25 mg/kg SC, once); (d) high dose extended-release buprenorphine (XR-hi, 6.5 mg/kg SC, once). On days -1, 0 (4 hours), 1, 2, and 3, mechanical and thermal hypersensitivities were evaluated, and plasma buprenorphine concentrations were measured. Results: Mechanical (days 0-2) and thermal (days 0-1) hypersensitivities were observed in the saline group. Bup-SR, XR-lo, and XR-hi attenuated mechanical hypersensitivity on days 0, 1, and 2. None of the treatment groups, except XR-Lo on day 0, attenuated thermal hypersensitivity on days 0 or 1. Plasma buprenorphine concentration peaked at 4 hours (day 0) in all treatment groups and remained greater than 1 ng/mL on days 0-2. No abnormal clinical observations or gross pathologic findings were seen in any groups. Conclusion: The results indicate XR-hi did not effectively attenuate post-operative hypersensitivity better than XR-lo. Thus both 3.25 and 6.5 mg/kg XR are recommended for attenuating post-operative hypersensitivity for at least up to 48 hours in mice.

Tiletamine/zolazepam and dexmedetomidine with tramadol provide effective general anesthesia in rats.

Background: Tiletamine/zolazepam is a dissociative anesthetic combination commonly used in small animals but information is limited in rats. The alpha-2 agonist, dexmedetomidine, has gained popularity in laboratory animal anesthesia. Tramadol is a weak opioid mu agonist. The aim of this study was to assess whether the tiletamine/zolazepam/dexmedetomidine (ZD) combination effectively provides a surgical anesthesia plane comparable to tiletamine/zolazepam/dexmedetomidine with tramadol (ZDT) in a minor procedure in rats. Methods: Rats were induced with ZD or ZDT. After the loss of paw withdrawal, a small incision was made on the rats' left thighs as a surgical stimulus. Rats were maintained under a surgical anesthesia plane by assessing the loss of the paw withdrawal reflex for 45 minutes, then atipamezole was administered. Monitored anesthesia parameters included: (a) physiological parameters - pulse rate (PR), respiratory rate (RR), tissue oxygen saturation (%SpO2), and body temperature; (b) duration parameters - induction time, onset and duration of surgical anesthesia plane, onset of recovery, and recovery time. Results: PR was significantly lower at 10 minutes in ZD and 5 minutes in ZDT groups. No difference was observed for RR, %SpO2, and body temperature. Likewise, there were no differences for duration parameters: induction time was less than 3 minutes; onset and duration of surgical anesthesia plane were approximately 5 and 45 minutes, respectively; onset of recovery (time to move) was 51 minutes; and recovery time was 52 minutes, respectively. Conclusion: These data suggest the ZD combination provides a surgical anesthesia plane comparable to ZDT in a rat incisional pain model.

Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus).

Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in a neonatal rat model of incisional pain. Male and female postnatal day 3 Sprague Dawley rat pups (n = 34) were randomly assigned to one of four treatment groups: 1) saline (control), 0.1 mL, once subcutaneously (SC); 2) buprenorphine HCl (Bup HCl), 0.05 mg/kg, once SC; 3) low dose Bup SR (low-SR), 0.5 mg/kg, once SC; 4) high dose Bup SR (high-SR), 1 mg/kg, once SC. Pups were anesthetized with sevoflurane and a 0.5-cm long skin incision was made over the left lateral thigh. The underlying muscle was dissected and closed using surgical glue. Thermal hypersensitivity testing was performed at 24 h prior to surgery and subsequently at 1, 4, 8, 24, and 48 h post-surgery using an infrared diode laser. Thermal hypersensitivity was attenuated at 1 h post-surgery in the Bup HCl group, while it was attenuated through the entire postoperative period in both low-SR and high-SR groups. This data suggests that a single dose of low-SR (0.5 mg/kg) or high-SR (1 mg/kg) effectively attenuates thermal hypersensitivity for at least 8 h in neonatal rat pups.

Effect of caffeinated and decaffeinated coffee on serum uric acid and uric acid clearance, a randomised within-subject experimental study.

OBJECTIVES: The effect of coffee on serum uric acid (SUA) has shown conflicting results. This study was to determine the effects of caffeinated coffee (CC) and decaffeinated coffee (DC) on SUA, serum xanthine oxidase activity (sXOA) and urine uric acid clearance (UAC). METHODS: This was a prospective randomised within-subject experimental study design of 51 healthy male participants. Each study period consisted of 3 periods, including a control, an intervention, and washout period for 1, 3 and 1 week, respectively. During the intervention period, the participants received 2, 4 or 6 gram/day of coffee, either CC or DC. RESULTS: For DC groups, SUA significantly decreased by 6.5 (±1.1) mg/dL to 6.2 (±1.1) mg/dL during the intervention period (p=0.014). sXOA significantly increased by 0.05 (±0.07) nmol/min/mL to 0.20 (±0.38) nmol/min/mL during the intervention period (p=0.010) of CC. For UAC, there was no significant change with CC or DC. In hyperuricaemic participants, SUA significantly decreased by 7.7 (±0.7) mg/dL to 7.2 (±0.7) mg/dL during the intervention period (p=0.028) of DC. For non-hyperuricaemic, CC significantly increased SUA by 5.9 (±0.7) mg/dL to 6.2 (±0.9) mg/dL during the intervention period (p=0.008) and significantly decreased SUA to 6.0 (±0.8) mg/dL (p=0.049) during the withdrawal period. A significant increase of sXOA according with SUA in CC groups from 0.05 (±0.07) nmol/min/mL to 0.25 (±0.44) nmol/min/mL during the intervention period (p=0.040) was presented in non-hyperuricaemic participants. CONCLUSIONS: DC had a significant decrease of SUA during the intervention period. However, in non-HUS participants, SUA significantly increased in CC.

The Stability and Efficacy of Tricaine Methanesulfonate (MS222) Solution After Long-Term Storage.

Tricaine methanesulfonate (MS222) is widely used for the anesthesia and euthanasia of laboratory zebrafish. Fresh solutions have been recommended for each use; however, researchers often mix and store concentrated stock solutions for convenience and to reduce occupational exposure and environmental waste. While this is common practice, published guidelines are often inconsistent. Thus, the objective of this study was to evaluate the stability and anesthetic efficacy of MS222 after long-term storage and to develop specific storage parameters. Stock solutions (100 mg/mL MS222) were mixed and stored in amber jars at 4 °C and -20 °C for 2- and 6-mo. Stability of the solutions was analyzed using liquid chromatography-ion trapmass spectrometry and compared with fresh MS222. Fifty adult (30 male, 20 female) wildtype AB zebrafish (Danio rerio) wererandomly anesthetized with 150 mg/L of one of the following MS222 solutions to evaluate anesthetic efficacy: 1) freshly prepared(0m); 2) 2 mo at 4 °C (2m4); 3) 2 mo at -20 °C (2m-20); 4) 6 mo at 4 °C (6m4); 5) 6 mo at -20 °C (6m-20). Time to cessation of swimming, loss of equilibrium, lack of response to von Frey (VF) stimulation, return of equilibrium, and resumption of swimming were compared between groups. Two fish from each group were euthanized at 24-h and 2-wk after anesthesia, and histopathology was performed. All solutions were determined to be stable under all storage conditions. No clinically significant differences were observed between the fresh and stored stock groups during anesthetic testing. No evidence ofanesthetic-related histologic changes were noted in the gills, skin, kidneys, muscle, and central nervous system. Hepatic megalocytosis and a reduction in hepatic vacuolation were seen to varying degrees across all groups, but did not follow a treatment-related trend. Therefore, 100 mg/mL solutions of MS222 can be stored in amber jars at 4 °C or -20 °C for 6 mo and still used to effectively anesthetize zebrafish.

Effects of Standard and Sustained-release Buprenorphine on the Minimum Alveolar Concentration of Isoflurane in C57BL/6 Mice.

Both standard and sustained-release injectable formulations of buprenorphine (Bup and BupSR, respectively) are used as preemptive analgesics, potentially affecting gas anesthetic requirements. This study tested the effects of Bup and BupSR on isoflurane requirements and confirmed that buprenorphine could reduce isoflurane requirements during a laparotomy in mice. We hypothesized that both Bup and BupSR would significantly decrease the required minimum alveolar concentration (MAC) of isoflurane. C57BL/6 mice received either isotonic crystalloid fluid (control), Bup (0.1 mg/kg), or BupSR (1.2 mg/kg) subcutaneously 10 min prior to the induction of anesthesia. Each anesthetized mouse was tested at 2 isoflurane concentrations. A 300-g noxious stimulus was applied at each isoflurane concentration, alternating between hindfeet. In addition, a subset of mice underwent terminal laparotomy or 60 min of anesthesia after injection with Bup, BupSR, or saline to ensure an appropriate surgical plane of anesthesia. Mice were maintained at the lowest isoflurane concentration that resulted in 100% of mice at a surgical plane from the aforementioned MAC experiments (control, 2.0%; Bup and BupSR, 1.7%). Analysis showed that both Bup and BupSR significantly decreased isoflurane requirements by 25.5% and 14.4%, respectively. The isoflurane MAC for the control injection was 1.80% ± 0.09%; whereas Bup and BupSR decreased MAC to 1.34% ± 0.08% and 1.54% ± 0.09%, respectively. Sex was not a significantly different between the injection groups during MAC determination. All of the mice that underwent surgery achieved a surgical plane of anesthesia on the prescribed regimen and recovered normally after discontinuation of isoflurane. Lastly, heart and respiratory rates did not differ between mice that underwent surgery and those that were anesthetized only. Bup and BupSR are MAC-sparing in male and female C57BL/6 mice and can be used for effective multimodal anesthesia.