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Capturing and handling wildlife is a common practice for both management and research. As telemetry use has become common, the need to capture and chemically immobilize wildlife has increased. Understanding how long the effects of immobilizing agents last after releasing the animal is often poorly understood but needed to ensure that analyses use data that reflect natural behavior. Between 2016 and 2021, 60 cougars (Puma concolor) were chemically immobilized with medetomidine, zolazepam, and tiletamine (MZT) and collared across west-central Alberta, Canada, 27 of which were individuals being recollared. We examined the distance an individual traveled per day and compared equivalent periods before and after the recollaring event to determine whether postcapture movement rates were significantly different from precapture rates. Within 1 d of the recollaring, daily movement rates had returned to precapture rates (t20-2.09, P=0.18). Our results provide insight on how MZT used in cougars affects their postcapture movement and thus may be helpful in interpreting movement data after release. [ABSTRACT FROM AUTHOR]

Introduction: The Sydney Medically Supervised Injecting Centre provides a safe, non‐judgemental space where people can inject pre‐obtained substances under the supervision of trained staff. This article describes an unusual incident occurring at the Medically Supervised Injecting Centre in January 2023. Case Presentation: Two regular male clients attending the Medically Supervised Injecting Centre injected a substance they believed to be cocaine. Both clients experienced adverse reactions; one was transported to hospital, while the other became extremely distressed and agitated. Paraphernalia sent for testing returned a result of tiletamine (a dissociative used in veterinary medicine) and no cocaine, 30 h after the incident. Discussion and Conclusions: Where substances are novel or unknown, adverse events are often unexpected and may be more difficult to prepare for. Substance‐induced acute agitation can be alarming and hazardous for people consuming drugs and those around them and may pose challenges for staff. There is a substantial evidence base for the benefits of on‐site drug analysis and drug checking in reducing harms related to drug use, and in enhancing drug market monitoring. This incident was successfully managed by Medically Supervised Injecting Centre and hospital staff, with no major consequence, however clinical management could have been improved using point of care drug testing. [ABSTRACT FROM AUTHOR]

The present study was undertaken to evaluate the effects of butorphanol, dexmedetomidine, tiletamine and zolazepam anaesthesia on blood gas and haematological parameters in cats. These parameters were monitored before anaesthetic induction and 10 minutes following anaesthetic induction. Statistical analysis revealed that no significant changes exist and the parameters were within the normal reference range for cats. Therefore, this anaesthetic technique could be employed safely for elective surgery in cats.

Simple Summary: Our study demonstrates that the immobilization of marmosets is best performed with a Telazol® dose of 5 mg/kg administered intramuscularly. This dose resulted in 50–90 min of immobilization, during which scientists and veterinarians can perform minimally invasive procedures. Marmosets' small body size makes anesthesia challenging. Ideally, small volumes of drugs should be administered intramuscularly (i.m.). In addition, dose-dependent sedation and anesthesia are desirable properties for sedatives and anesthetics in marmosets. Telazol® (tiletamine and zolazepam) is highly concentrated, allowing the use of small injection volumes and dose-dependent sedation and anesthesia. A randomized, blinded study with crossover design in ten healthy adult common marmosets (Callithrix jacchus) was performed to evaluate the anesthetic and cardiorespiratory effects of three doses of i.m. Telazol® (respectively, 5, 10, and 15 mg/kg). Depth of anesthesia, cardiorespiratory effects, and induction, immobilization, and recovery times were determined. A significant difference was observed in immobilization time between 5 and 15 mg/kg of Telazol®. In addition, 15 mg/kg of Telazol® resulted in increased recovery times compared to 5 mg/kg. The cardiorespiratory effects during the first 45 min of immobilization were within clinically acceptable limits. The pedal withdrawal reflex was the best indicator of the anesthetic depth. [ABSTRACT FROM AUTHOR]

The present study was conducted on eighteen horses divided into three groups, consisting of six horses in each irrespective of their size, breed and body weight. Horses from all groups were pre-anaesthetized with xylazine (1.1 mg/kg b.wt.) intravenously and anesthetized after 5 min with doses of zoletil (Tiletamine and zolazepam) @ 0.5 mg/kg, 0.8 mg/kg and 1.1 mg/kg BW in groups I, II and III, respectively. Evaluation of different parameters like time of induction of anaesthesia, quality of induction, duration of anaesthesia, degree of muscle relaxation, time and quality of recovery were evaluated and compared between the groups. Different haematological, biochemical and clinical parameters were studied before administration of pre-anaesthetic, during anaesthesia and after complete recovery. There was no significant difference noted for clinical, haematological, biochemical and anaesthetic parameters between the three groups. Quality of induction and anaesthesia was better in group II and group III than group I. Time required attaining sternal recumbency, standing and completing recovery were significantly longer in group III than group I and group II. Overall quality of recovery was better in group I and group II than group III. On the basis of this study, we can say zoletil at a dose rate of 0.8 mg per kg body weight provide better quality of field anaesthesia associated with smooth recovery for short term surgical procedures like gelding. [ABSTRACT FROM AUTHOR]

The present study was undertaken to evaluate the effects of butorphanol, dexmedetomidine, tiletamine and zolazepam anaesthesia on blood gas and haematological parameters in cats. These parameters were monitored before anaesthetic induction and 10 minutes following anaesthetic induction. Statistical analysis revealed that no significant changes exist and the parameters were within the normal reference range for cats. Therefore, this anaesthetic technique could be employed safely for elective surgery in cats. [ABSTRACT FROM AUTHOR]

Laboratory animals are commonly anesthetized to prevent pain and distress and to provide safe handling. Anesthesia procedures are well-developed for common laboratory mammals, but not as well established in reptiles. We assessed the performance of intramuscularly injected tiletamine (dissociative anesthetic) and zolazepam (benzodiazepine sedative) in fixed combination (2 mg/kg and 3 mg/kg) in comparison to 2 mg/kg of midazolam (benzodiazepine sedative) in ball pythons (Python regius). We measured heart and respiratory rates and quantified induction parameters (i.e., time to loss of righting reflex, time to loss of withdrawal reflex) and recovery parameters (i.e., time to regain righting reflex, withdrawal reflex, normal behavior). Mild decreases in heart and respiratory rates (median decrease of

There has been a significant increase in veterinary drugs found on toxicology screens and postmortem analyses, especially in the Northeast region of the US. This article details the effects and treatment of two common culprits: xylazine and tiletamine-zolazepam. [ABSTRACT FROM AUTHOR]

Abstract 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.

Zoletil is a combination of tiletamine hydrochloride and zolazepam hydrochloride used as a veterinary anesthetic. Although zoletil abuse is widely known, zoletil poisoning for the purpose of suicide is very rare. We present a case of a 39-year-old man who attempted suicide by intravenously injecting a large amount of zoletil, resulting in decreased mental status and severe respiratory depression. Intubation and mechanical ventilation were applied. After 30 hours in the hospital, all symptoms of poisoning improved. Because zoletil can cause severe respiratory depression, close observation and aggressive securement of an airway is mandatory

In spite of significant advancement in the field of gaseous anaesthesia, the injectable agents still favoured in field condition for surgical management in small ruminant like goat. In the present study three anaesthetic combinations from benzodiazepine (zolazepam and midazolam), dissociative agents (ketamine and tiletamine) and alpha2 agonist (medetomidine) were tested in goat. All total fifteen numbers of clinical cases requiring surgical intervention were equally divided into three groups viz. group I, II and III. Group I was subjected to midazolam and ketamine; group II was injected with tiletamine and zolazepam and group III was injected with medetomidine and ketamine to select best anaesthetic protocol. The shortest induction time was recorded in group I (3.2±0.58 minutes) followed by group II (3.8±0.37 minutes) and group III (5.12±0.15 minutes). The duration of anaesthesia was highest in group III (123.40±4.63 minutes), followed by group II (60±3.32 minutes) and group I (44.80±2.35 minutes). All the groups exhibited smooth and uneventful induction and recovery; however, analgesia was recorded poor in group II. The clinic-physiological and biochemical changes in all the groups revealed minimal variation within physiological limit during entire observation period. Following completion of the observations, it could be concluded that the combination of midazolam @ 0.4 mg-ketamine @ 4 mg/kg b.wt. and tiletamine-zolazepam @ 3 mg/kg b.wt. could be used for short term anaesthesic procedures like castration while the combination of medetomidine @ 20 μg/kg-ketamine @ 5 mg/kg b.wt. could be used for surgical procedures of longer duration. [ABSTRACT FROM AUTHOR]

Pig experiments often require anaesthesia, and a rapid stress-free induction is desired. Induction drugs may alter the subsequent anaesthesia. Therefore, the aim of the present study was to compare, in pigs, the effects of two different injectable anaesthetic techniques on the induction and on the physiological variables in a subsequent eight hours of total intravenous anaesthesia (TIVA). Twelve domestic castrates (Swedish Landrace/Yorkshire) 27‒31 kg were used. The pigs were randomly assigned to different induction drug combinations of zolazepam–tiletamine and medetomidine intramuscularly (ZTMe) or midazolam, ketamine intramuscularly and fentanyl intravenously (MiKF). Time from injection to unconsciousness was recorded and the ease of endotracheal intubation assessed. The TIVA infusion rate was adjusted according to the response exhibited from the nociceptive stimulus delivered by mechanically clamping the dewclaw. The time from injection to unconsciousness was briefer and intubation was easier in the ZTMe group. Results from the recorded heart rate, cardiac index and arterial blood pressure variables were satisfactorily preserved and cardiovascular function was maintained in both groups. Shivering was not observed in the ZTMe group, but was observed in four of the pigs in the MiKF group. The requirement of TIVA was lower in the ZTMe group. In conclusion, ZTMe had better results than MiKF in areas such as shorter induction time, better intubation scoring results and less adjustment and amount of TIVA required up to six hours of anaesthesia. The results may have been due to a greater depth of anaesthesia achieved with the ZTMe combination at the dose used. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the anesthetic and cardiopulmonary effects of dexmedetomidine in combination with tiletamine (without zolazepam) as a general anesthetic. The study was divided into two phases. In Phase 1, 18 adult healthy mixed-breed dogs were randomly allocated into three groups: Group TD8 (4.5 mg kg−1 tiletamine and 8 μg kg−1 dexmedetomidine), Group TD10 (4.5 mg kg−1 tiletamine and 10 μg kg−1 dexmedetomidine), or Group TD12 (4.5 mg kg−1 tiletamine and 12 μg kg−1 dexmedetomidine). After drug administration, the heart rate (HR), respiratory rate (fR), mean arterial pressure (MAP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), peripheral hemoglobin oxygen saturation (SpO2), behavioral score, quality of induction and recovery, extent of ataxia, the time taken for induction, and the duration of anesthesia were recorded. The recovery time and quality were recorded after administration of atipamezole (50 μg kg−1) after 60 min. In phase 2, the feasibility of combining dexmedetomidine (10 μg kg−1) and tiletamine (4.5 mg kg−1) as general anesthetics for orchiectomy was evaluated in dogs (n = 6). HR, fR, MAP, SAP, DAP, temperature, SpO2, behavioral scores, and adverse reactions were recorded during each surgical procedure. In phase 1, the dogs were anesthetized for 5 min after administration of drugs and achieved a maximum behavioral score in TD10 and TD12 after 10 min. Although HR, MAP, SAP, DAP, and NIBP decreased in all three groups, they still maintained within the normal range. In phase 2, orchiectomy was completed smoothly in all dogs with little fluctuation in the physiological variables. We found that a combination of tiletamine (4.5 mg kg−1) and dexmedetomidine (10 μg kg−1) intramuscularly induced moderate anesthesia in dogs and could be utilized for short-term anesthesia and minor surgery.

Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry （GC-QTOF-MS）. Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.

Introduction: Tiletamine-xylazine-tramadol (XFM) has few side effects and can provide good sedation and analgesia. Adenosine 5’-monophosphate-activated protein kinase (AMPK) can attenuate trigeminal neuralgia. The study aimed to investigate the effects of XFM and its specific antagonist on AMPK in different regions of the brain. Material and Methods: A model of XFM in the rat was established. A total of 72 Sprague Dawley (SD) rats were randomly divided into three equally sized groups: XFM anaesthesia (M group), antagonist (W group), and XFM with antagonist interactive groups (MW group). Eighteen SD rats were in the control group and were injected intraperitoneally with saline (C group). The rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus, and brain stem were immediately separated, in order to detect AMPKα mRNA expression by quantitative PCR. Results: XFM was able to increase the mRNA expression of AMPKα1 and AMPKα2 in all brain regions, and the antagonist caused the opposite effect, although the effects of XFM could not be completely reversed in some areas. Conclusion: XFM can influence the expression of AMPK in the central nervous system of the rat, which can provide a reference for the future development of anaesthetics for animals.

Objective: To determine incidence and risk factors of post-sterilization hyphema in shelter cats. Animals studied: Retrospective medical record review of 1204 cats and prospective screening of 195 cats. Procedures: The study consisted of three parts: (a) Survey responses were collected from 20 veterinarians, who perform high-quality high-volume spay-neuter (HQHVSN) in both shelter and public clinic settings; (b) medical records of 1204 cats were analyzed retrospectively over a 14-month time period; and (c) ophthalmic examinations, including tonometry, were performed prospectively on 195 cats before and after sterilization surgery over 8 weeks. Results: Nine of 20 surveyed veterinarians reported having witnessed hyphema in cats following sterilization surgery. Retrospective review of 1204 medical record and prospective screening of 195 cats showed that three juvenile (<1 year of age) male cats (<2 kg) developed hyphema within 1 hour following surgery (0.2% incidence). In all three affected cats, anesthesia was induced with tiletamine/zolazepam (3 of 523 cats induced with this drug combination; 0.6% incidence), and hyphema resolved within 20 hours. Mean intraocular pressures as measured by Icare® TonoVet were (mean ± standard deviation) 11.5 ± 3.8 mm Hg and 21.7 ± 4.6 mm Hg for juvenile (<1 year of age) and adult (>1 year of age) cats, respectively. Conclusions: Survey responses and three observed cases confirm the existence of feline post-sterilization hyphema with an estimated incidence of 0.2%. The underlying mechanism for this occurrence remains unknown. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the effects of medotomidine-ketamine anesthesia and zolazepamtiletamine anesthesia on hematological and biochemical parameters and to investigate its clinical applicability. The study material consisted of 32 cats. There were 19 female and 13 male cats. The cats were between 6 months and 3 years and had a live weight of 5.3 ± 2.4 kg. Our study; medetomidine (80 mcg/kg im)-ketamine (10 mg/kg im) group (Group I) consisted of 16 cats and zolazepam-tiletamine (15 mg/kg im) group (Group II) consisted of 16 cats. Of all cats, 0 minutes, 120 minutes, 12. hours and 24 hours. Blood was taken for v. cephalica antebrachidene for hematological and biochemical measurements. In statistical evaluation; Between the two groups; There was a significant difference in hemoglobin (HGB) 120th minute and lymphocyte (LENF) 24th hour, leukocyte (WBC) 0 minutes, blood urea nitrogen (BUN) 12th hour, glucose (GLU) 120th minute measurements were significantly different (P<0.05). HGB, LENF, WBC, creatine (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and GLU measurements in the 1st and 2nd groups of the 0th minute, 120th minute, 12th hour and 24th hour measurements, granulocyte (GRAN) and eosinophils (EOS) measurements in the first group the 0th minute, 120th minute, 12th hour and 24th hour, in the second group of gamma glutamil tranpeptidase (GGT) measurements, there was a significant difference between the measurements at 0th, 120th minutes, 12th and 24th hours (P<0.05). As a result; the effects of medotomidine-ketamine and zolazepam-tiletamine anesthesia on hematological and biochemical parameters in cats were determined, but this effect remained within physiological limits. However, in terms of anesthesia findings, medotomidine-ketamine anesthesia was found to provide better anesthesia than zolazepam- tiletamine anesthesia. [ABSTRACT FROM AUTHOR]

Laboratory mice are commonly euthanised with carbon dioxide (CO2); however, there is ample evidence that this gas is aversive. Previous work suggests that sedation achieved via injection with benzodiazepines prior to CO2 administration could reduce aversive behaviours during euthanasia. We explored the potential of using a voluntarily ingested sedative (tiletamine-zolazepam, Zoletil®) prior to euthanasia. Male and female C57BL/6 mice were allocated into one of the five experimental groups, which differed in the dose of Zoletil: 0, 10, 20, 40, 80 or 100 mg/kg. A dose of 20 mg/kg was found to achieve mild sedation prior to euthanasia; mice which received this dose numerically reared and walked on the cage lid less, and showed ataxia, immobility and recumbency for longer than mice that received a lower dose. During euthanasia, mice that received 20 mg/kg showed fewer aversive responses to CO2. Doses of 40 to 100 mg/kg were associated with signs of moderate to severe sedation, but resulted in an incomplete intake of the sedative, which made the interpretation of the aversiveness to CO2 difficult. Voluntary oral administration of a sedative is an effective, affordable, and easy way to minimize the stress of mice to euthanasia with CO2.

The family context has been associated with children's weight status. This study aims to investigate the association of parents' adherence to the Mediterranean diet and family time with the weight status of children. The research is part of BeE-school, a cluster-randomized trial implemented in primary schools located in socially vulnerable contexts. A total of 735 children (380 boys and 355 girls) aged 6 to 10 participated in the study. Anthropometrics were assessed during school time, and weight status was categorized, while parents self-reported sociodemographic variables, adherence to the Mediterranean diet (MEDAS questionnaire), and family time. Children from families with higher education levels whose parents have a high adherence to the Mediterranean diet have lower odds of overweight/obesity (odds ratio (OR) 0.301, 95% CI 0.143-0.634, p = 0.002). Also, children from families with lower education levels who have more time together with their family have lower odds of overweight/obesity (OR 0.731, 95% CI 0.573-0.934, p = 0.012). The family environment, mainly family time together and adherence to the Mediterranean diet, exerts a significant influence on children's weight status. Professionals working in children's health should consider the family when fostering health-promoting behaviors.

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Pigs are widely used in metabolic research with procedures often requiring general anaesthesia. The aim was to investigate the effect of four different anaesthetic protocols: 1) isoflurane inhalation, 2) propofol infusion, 3) a mixture of tiletamine, zolazepam, medetomidine, ketamine and butorphanol (TZMKB)) and 4) ketamine combined with midazolam and xylazine (KMX)) on selected biomarkers during basal and glucose stimulated conditions. Eight domestic pigs were included in a cross-over design. Plasma concentrations of glucose, insulin, C-peptide, glucagon, cortisol, triglycerides, total cholesterol, aspartate amino transferase and alanine amino transferase, creatinine, urea, fructosamine, albumin, free fatty acids (FFAs) and glycerol were measured at baseline, during 2 h of anaesthesia and during 1 h of recovery. Intravenous glucose tolerance test (IVGTT, 0.5 g glucose/kg) was performed after 1 h of anaesthesia. Glucose disappearance rate and areas under the insulin, C-peptide and glucagon curves from the IVGTT were calculated. All four anaesthetic protocols affected glucose metabolism parameters significantly compared with un-anaesthetised pigs, which was particularly evident during IVGTT and for TZMKB and KMX anaesthesia. Propofol additionally influenced the plasma concentrations of triglycerides, FFAs and glycerol significantly. The remaining circulating biomarkers were largely unaffected by anaesthesia. These data underline the importance of considering the anaesthetic protocol in porcine studies of circulating metabolic biomarkers., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The association of tiletamine with zolazepam (T/Z) is commonly used in dissociative anesthesia in household pets. This combination induces short-duration somatic analgesia, loss of voluntary movements and myorelaxation caused by the benzodiazepin, with stimulation of the ardiovascular system and maintenance of protective reflexes. Due to the large use of this association in elective neutering of felines and its anesthetic properties, we chose to monitorize and identify electrocardiographic (ECG) and clinical changes during the anesthetic procedure, with and without oxygen supplementation. For this study, 20 female felines were recruited. All animals were young adults, healthy, no specific breed. The subjects underwent clinical, laboratorial and electrocardiographic evaluations prior to anesthesia. Tramadol hydrochloride was given as Preanesthetic medication followed by anesthesia with T/Z. The felines were randomly assigned to either Group 1 (n=10), in which subjects received oxygen supplementation through mask during the anesthetic procedure, or Group 2 (n=10), in which subjects were not supplemented with oxygen. Heart and respiratory rates, systolic blood pressure, rectal temperature and pulse oxymetry were monitored in all subjects from both groups. We also obtained recordings of the ECG tracing and derivations for each animal which were posteriorly evaluated and interpreted. The results showed significant differences between the groups in respiratory rate (G1 = 26,8 +/- 2,1 and G2= 38,5+/- 3,2) and pulse oxymetry (G1= 97,3 +/- 2,4% and G2 = 91,2 +/- 1,1%). We also observed on the ECG recordings development of periods of intermittent right branch blockage and S-T elevation in both groups. We therefore concluded that the ECG recordings were identical in both groups despite oxygenotherapy; however, we observed an improvement in the clinical parameters in animals who received oxygen supplementation via mask.

The aim of this study was evaluate the effects of three anesthetic combinations, ketamine-midazolam, ketamine-xylazine and tiletamine-zolazepam, on IOP in rabbits. In a experimental, blind, randomized, crossover study, six rabbits were anesthetized with each of 3 treatments in random order. Groups KM (ketamine, 30 mg/kg + midazolam, 1 mg/kg); KX (ketamine, 30 mg/kg + xylazine, 3 mg/kg); and TZ (tiletamine + zolazepam, 20 mg/kg). The drugs were mixed in the same syringe injected intramuscularly (IM) into the quadriceps muscle. IOP was measured before drug administration (baseline) and at 5-minute intervals for 30 minutes. The data were analyzed by a 2-way repeated measures ANOVA followed by Bonferroni test. All groups had significant decreases in IOP compared to baseline (p < 0.001). There was no difference between groups at any of the time points assessed (p > 0.05). Administration of either ketamine-midazolam, ketamine-xylazine, or tiletamine-zolazepam similarly decrease IOP in rabbits within 30 minutes of injection.

The glutamate N-methyl- d-aspartate (NMDA) receptor antagonist ketamine (KET) produces rapid and sustained antidepressant effects in patients. Tiletamine (TIL; 2-ethylamino-2-thiophen-2-yl-cyclohexan-1-one) is another uncompetitive NMDA receptor antagonist, used in a medical (veterinary) setting as an anesthetic tranquilizer. Here, we compared the behavioral actions of KET and TIL in a variety of tests, focusing on antidepressant-like and dissociative-like effects in mice and rats. The minimum effective doses of KET and TIL were 10 mg/kg to reduce mouse forced swim test immobility and 15 mg/kg to reduce marble-burying behavior. However, at similar doses, both compounds diminished locomotor activity and disturbed learning processes in the mouse passive avoidance test and the rat novel object recognition test. KET and TIL also reduced social behavior and accompanying 50-kHz 'happy' ultrasonic vocalizations (USVs) in rats. TIL (5-15 mg/kg) displayed additional anxiolytic-like effects in the four-plate test. Neither KET nor TIL affected pain response in the hot plate test. Examination of the 'side effects' revealed that only at the highest doses investigated did both compounds produce motor deficits in the rotarod test in mice. While KET produced behavioral effects at doses comparable between species, in the rats, TIL was ~10 times more potent than in the mice. In summary, antidepressant-like properties of both KET and TIL are similar, as are their adverse effect liabilities. We suggest that TIL could be an alternative to KET as an antidepressant with an additional anxiolytic-like profile. [ABSTRACT FROM AUTHOR]

Pigs are commonly used in diabetes research due to their many physiological similarities to humans. They are especially useful in imaging procedures because of their large size. However, to achieve imaging procedures the pig must lie completely still, and thus needs to be anaesthetized. Most anaesthetic drugs used in laboratory animals affect carbohydrate metabolism by the inhibition of insulin release. The aim of this pilot study was primarily to develop an anaesthetic protocol for pigs that did not have an effect on blood glucose levels throughout the 3 h of anaesthesia; and secondly, to evaluate the most promising protocol in combination with an oral glucose tolerance test (OGTT). Two anaesthetic protocols were used in four growing pigs. Intravenous propofol infusion caused hyperglycaemia in three out of four pigs within 5-10 min after induction and was therefore excluded. Intravenous infusion with tiletamine, zolazepam and butorphanol (TZB) for 3 h did not affect blood glucose levels. The pigs underwent OGTT twice, once without anaesthesia and once with TZB induction after glucose intake. Anaesthesia during OGTT resulted in a lower area under the curve (AUC) of glucose (P < 0.05), higher AUC of glucagon (P < 0.05) and an insulin response less than 10% of that during OGTT without anaesthesia. In conclusion, long-term infusion anaesthesia with TZB does not affect glucose homeostasis in pigs. However, the protocol is not effective when combined with OGTT, as glucose, insulin and glucagon levels are affected. [ABSTRACT FROM AUTHOR]

The Asiatic black bear ( Ursus thibetanus; ABB) is a globally endangered species for which a restoration program has been ongoing in South Korea since 2001. However, there is little information on immobilization protocols for ABBs. We evaluated the use of medetomidine-zolazepam-tiletamine for their immobilization. During 2005-13, we anesthetized 60 ABBs (32 males, 28 females; 7 mo to 12 yr old) with medetomidine 0.03-0.045 mg/kg and zolazepam-tiletamine 1.54-2.3 mg/kg; reversal of anesthesia was done with atipamezole 0.15-0.225 mg/kg administered intravenously alone or intravenously and intramuscularly (50:50). Mean (and SD) for physiologic collected for 373 immobilizations of at least 60 min were: time to sedation, 7.8 (5.4) min; anesthesia induction time, 13.7 (8.1) min; complete recovery time, 14.8 (12.4) min; respiratory rate, 14 (7) breaths/min; heart rate, 51 (16) beats/min; rectal temperature, 37.3 (1.3) C; and hemoglobin oxygen saturation, 88% (6%). Few cardiopulmonary side effects occurred during immobilization and adequate depth of anesthesia was maintained for >60 min without need for supplementation. The dosage and drug combination used was effective for immobilization of ABBs with minimal adverse effects on vital signs and can be recommended in most clinical applications. [ABSTRACT FROM AUTHOR]

The purpose of the current study was to compare intranasal (IN) and intramuscular (IM) administration of zolazepam-tiletamine (ZT) combination in cats. Eight adult healthy cats weighing 2.47 ± 0.6 kg were used. Each animal received 10 mg/kg ZT combination by IN and IM routes with a minimum one week intervals. The onset of sedation, the length of surgical anaesthesia and the recovery time were recorded. The parameters were recorded immediately before and at 5, 10, 15, 20, and 30 min after administration of ZT combination. No anaesthetic complication was observed in either administration route. Recovery was uneventful in all animals. There were no statistical differences between the IN and IM administration with respect to onset of sedation and the length of anaesthesia. Recovery time was significantly shorter when the ZT combination was administered IN route (30.63 ± 0.32 min) compared to IM injection (33.38 ± 0.32 min). The route of administration of the ZT combination had no effect on heart rate (P = 0.388), respiratory rate (P = 0.628), rectal temperature (P = 0.066), and peripheral haemoglobin oxygen saturation (P = 0.442). Intranasal administration of ZT combination can be an alternative technique for sedation in cats. [ABSTRACT FROM AUTHOR]

Anesthetics utilized for the immobilization of pregnant mammals are prone to crossing the placental barrier and cause adverse effects to the fetuses. In this study, we develop a facile method employing high performance liquid chromatography (HPLC) for the study of Telazol crossing the placental barrier of pregnant pigs. The method mainly relies on the efficient extraction strategy that includes the mobile phase composed of 10 mM ammonium acetate aqueous solution-acetonitrile (1:4, v/v). When the injected dose of Telazol is 10 mg/kg (5 mg/kg of each constituent drug, zolazepem and tiletamine), zolazepam can cross the placental barrier as it is detected in both uterus and umbilical cord with approximately the same content. Conversely, tiletamine is detected in neither uterus nor umbilical cord, indicating the absence of placental transfer of tiletamine. The different absorption rates of the two dosage-equal compounds by pigs are found to be the main cause of their different abilities to cross the placental barrier. [ABSTRACT FROM AUTHOR]

Tiletamine is a non-competitive N -methyl- d -aspartate (NMDA) receptor antagonist chemically related to ketamine and phencyclidine. A common veterinary anesthetic drug, tiletamine is currently a Schedule III controlled substance in USA. This compound exerts sedative effects in humans and animals, also having an abuse potential, toxicity and dissociative hallucinogenic properties clinically. However, the neurotropic profile of tiletamine remains poorly understood, necessitating novel models and in-vivo screens, including non-mammalian species. Zebrafish ( Danio rerio ) are rapidly becoming a popular model organism for screening various CNS drugs, including those acting at NMDA receptors. Here, we investigated acute behavioral effects of 1, 5 and 10 mg/L of tiletamine on adult zebrafish. In the standard novel tank test, a 20-min immersion in 1 mg/L of tiletamine produced no overt differences from control zebrafish (receiving 0.1% DMSO vehicle), except for reduced top entries. In contrast, tiletamine at 5 and 10 mg/L exerted robust dose-dependent sedative effects in zebrafish (also darkening their skin coloration, similar to ketamine and PCP). Gas chromatography/mass spectrometry (GC/MS) analyses revealed no tiletamine peaks in control and 1 mg/L groups, but detected tiletamine peaks in zebrafish brain samples at 5 and 10 mg/L. Together, these findings demonstrate potent neurotropic effects of tiletamine in zebrafish, and their high sensitivity to this drug. Our findings also support the growing utility of fish-based aquatic screens for studying neuroactive properties of NMDA antagonists in-vivo. [ABSTRACT FROM AUTHOR]

We describe the use of a combination of tiletamine and zolazepam (Zoletil®) for chemical restraint of South American coatis ( Nasua nasua) under field conditions. We immobilized 53 coatis from a free-ranging population at Iguaçu National Park, Brazil, with Zoletil. Males and females (1.0-8.7 kg) of different age groups participated in the study. Four dosage (milligram per kilogram body weight) groups were created based on quartiles as follows: 1) 4.76-6.68 mg/kg ( n=13), 2) 6.83-7.71 mg/kg ( n=13), 3) 7.72-8.68 mg/kg ( n=18), and 4) 8.98-11.57 mg/kg ( n=9). Variables analyzed were sex, age, body weight, dosage, induction time, handling time (HT: time elapsed between the onset of immobilization and first signs of recovery), time from injection to first stand-up posture after anesthesia, heart and respiratory rates, and body temperature. Mean (±SD) induction time was 2.9 (±1.4) min and was positively correlated with age. In dosage groups 1-4, mean HTs were 40.3 (±24.0), 64.5 (±19.1), 54.8 (±15.0), and 60.3 (±12.0), respectively. Handling time had a positive linear relationship with age and body weight, but the relationship between HT and dosage was nonlinear. Group 1 had a shorter HT compared to the other groups combined. Time from injection to first stand-up was 105.0 (±33.5) min. Zoletil was quick acting and safe for immobilization of coatis in the wild. [ABSTRACT FROM AUTHOR]

This study investigated the induction of anesthesia in swine by injection of tiletamine/zolazepam and ketamine in combination with either dexmedetomidine (TKD) or xylazine (TKX). We hypothesized that TKD would accelerate anesthesia onset and prolong recovery as compared TKX in swine undergoing a noninvasive radiographic procedure. A randomized crossover experiment was performed on 6 healthy, intact, male miniature swine undergoing radiographic examination. Swine were randomly assigned to one of 2 groups: 1) 5mg/kg tiletamine/zolazepam, 2.5mg/kg ketamine, and 0.0125mg/kg dexmedetomidine (TKD) or 2) 5mg/kg tiletamine/zolazepam, 2.5mg/kg ketamine, and 2.5mg/kg xylazine (TKX). Either TKD or TKX was administered intramuscularly at 0.05mL/kg to provide anesthesia for a 45-min radiographic procedure. At 45min after drug administration, atipamezole was administered. During anesthesia, swine were monitored for duration parameters (time to sternal recumbency [onset of anesthesia], lateral recumbency, loss of palpebral reflex, return of the palpebral reflex, and return to sternal recumbency [onset of recovery]) and physiologic parameters (heart rate, %SpO₂, noninvasive blood pressure, and body temperature). Duration and physiologic parameters did not differ between groups at any time point. The results indicate TKD and TKX provide comparable general anesthesia in swine undergoing a radiographic examination.

Objective: Few clinical prediction models are available to clinicians to predict the recovery of patients with post-collision neck pain and associated disorders. We aimed to develop evidence-based clinical prediction models to predict (1) self-reported recovery and (2) insurance claim closure from neck pain and associated disorders (NAD) caused or aggravated by a traffic collision., Methods: The selection of potential predictors was informed by a systematic review of the literature. We used Cox regression to build models in an incident cohort of Saskatchewan adults (n = 4923). The models were internally validated using bootstrapping and replicated in participants from a randomized controlled trial conducted in Ontario (n = 340). We used C-statistics to describe predictive ability., Results: Participants from both cohorts (Saskatchewan and Ontario) were similar at baseline. Our prediction model for self-reported recovery included prior traffic-related neck injury claim, expectation of recovery, age, percentage of body in pain, disability, neck pain intensity and headache intensity (C = 0.643; 95% CI 0.634-0.653). The prediction model for claim closure included prior traffic-related neck injury claim, expectation of recovery, age, percentage of body in pain, disability, neck pain intensity, headache intensity and depressive symptoms (C = 0.637; 95% CI 0.629-0.648)., Conclusions: We developed prediction models for the recovery and claim closure of NAD caused or aggravated by a traffic collision. Future research needs to focus on improving the predictive ability of the models., (© 2023. Chiropractic and Osteopathic College of Australasia, European Academy of Chiropractic, The Royal College of Chiropractors, Nordic Institute of Chiropractic and Clinical Biomechanics and BioMed Central Ltd.)

Background and Objectives: Female-specific factors and psychosocial factors may be important in the prediction of stroke but are not included in prediction models that are currently used. We investigated whether addition of these factors would improve the performance of prediction models for the risk of stroke in women younger than 50 years., Methods: We used data from the Stichting Informatievoorziening voor Zorg en Onderzoek, population-based, primary care database of women aged 20-49 years without a history of cardiovascular disease. Analyses were stratified by 10-year age intervals at cohort entry. Cox proportional hazards models to predict stroke risk were developed, including traditional cardiovascular factors, and compared with models that additionally included female-specific and psychosocial factors. We compared the risk models using the c -statistic and slope of the calibration curve at a follow-up of 10 years. We developed an age-specific stroke risk prediction tool that may help communicating the risk of stroke in clinical practice., Results: We included 409,026 women with a total of 3,990,185 person-years of follow-up. Stroke occurred in 2,751 women (incidence rate 6.9 [95% CI 6.6-7.2] per 10,000 person-years). Models with only traditional cardiovascular factors performed poorly to moderately in all age groups: 20-29 years: c -statistic: 0.617 (95% CI 0.592-0.639); 30-39 years: c -statistic: 0.615 (95% CI 0.596-0.634); and 40-49 years: c -statistic: 0.585 (95% CI 0.573-0.597). After adding the female-specific and psychosocial risk factors to the reference models, the model discrimination increased moderately, especially in the age groups 30-39 (Δ c -statistic: 0.019) and 40-49 years (Δ c -statistic: 0.029) compared with the reference models, respectively., Discussion: The addition of female-specific factors and psychosocial risk factors improves the discriminatory performance of prediction models for stroke in women younger than 50 years., (© 2023 American Academy of Neurology.)