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Specific Diseases and Procedures
Published in Michele Barletta, Jane Quandt, Rachel Reed, Equine Anesthesia and Pain Management, 2023
Drugs. Combine with cardiac massage epinephrine 0.01 mg/kg IV.Doxapram is a respiratory stimulant and also will partially antagonize sedation from xylazine or detomidine passed through the placenta from the mare. Inject 0.5 mg/kg, approximately 1.25 ml for a large foal, intravenously.Antagonism of drugs administered to the mare that may have crossed to the foal. Naloxone is an opioid antagonist. Inject 0.01 mg/kg, approximately 1.0 ml (0.4 mg/ml, for a large foal). Atipamezole will antagonize an alpha-2 agonist sedative.Dopamine and dobutamine are cardiovascular stimulants. Dopamine is more effective for resuscitation because it increases heart rate in addition to myocardial contractility. Add 50 mg dopamine (1.25 ml of 40 mg/ml) to 500 ml saline to make a solution of 100 µg/ml. Infuse IV at 7–10 µg/kg/min; for a 50 kg/110 lb foal, 8 µg/kg/min using a 15 drops/ml administration set is one drop/second.Tactile stimulation by rubbing with a towel; tickle inside the nostrils and ears and the perineum.
Neuroimaging Applications for the Study of Alzheimer’s Disease
Published in Zaven S. Khachaturian, Teresa S. Radebaugh, Alzheimer’s Disease, 2019
Most α2-adrenoceptors are thought to correspond to the inhibitory presynaptic autoreceptors, thus stimulation would lead to a decrease in synaptic noradrenaline content.93 An interesting observation of the effect of an α2 agonist is the profound effect of dexmedetomidine on enhancing gas anesthesia and the antidotal effect of the antagonist atipamezole in reversing this effect. The high affinity of atipamezole, 0.2 nM, lead us to evaluate the ability of this ligand to quantitate the distribution of the α2 system.58 The observation that the antagonists label both high- and low-affinity states of the α2 system has been forwarded as a rationale for favoring agonists rather than antagonists if the labeling chemistry and biodistribution kinetics are acceptable.
Reviving matrix for nerve reconstruction in rat model of acute and chronic complete spinal cord injury
Published in Neurological Research, 2022
Shimon Rochkind, Mara Almog, Zvi Nevo
Noninvasive electrophysiology evaluation was performed before the surgical procedure and again at the end of study. The recordings were performed from both hindlimbs using a Dantec® KEYPONT® Focus device (Natus Medical Inc., USA). The measurements were conducted on anesthetized rats using an intraperitoneal injection of ketamine (60 mg/kg; Vetmarket, Israel) and medetomidine (0.25 mg/kg; Vetmarket, Israel) mixture. Bipolar stimulating needle electrodes were placed at the gastrocnemius muscle (cathode) and another one subcutaneously at the foot pad level (anode). The somatosensory evoked potentials (SEPs) were recorded through bipolar needle electrodes, when one needle electrode placed subcutaneously between the eyes (anode) and the other over the approximate location of the somatosensory cortex (cranial level) and served as a cathode. For ground, an electrode was placed subcutaneously in the lumbar region. Throughout the evaluation an average of 300 single pulses was delivered having a duration of 0.2 ms at a rate of 3/sec. The stimulus intensity was increased gradually, until appearance of twitching of the hindlimb. Then, somatosensory evoked potentials (SEPs) were recorded. At the end of the measurement the rats received an intraperitoneally dose of atipamezole hydrochloride (Vetmarket, Israel), as an antidote (1 mg/kg). The appearance of a SEP signal in two consecutive tests was considered positive.
Transplantation of rat pancreatic islets vitrified-warmed on the nylon mesh device and the silk fibroin sponge disc
Published in Islets, 2020
Kenyu Nakayama-Iwatsuki, Takahiro Yamanaka, Jun Negishi, Junki Teshima, Yasushi Tamada, Masumi Hirabayashi, Shinichi Hochi
On the day of islet transplantation (defined as Day-0), the diabetic rats were anesthetized by the inhalation of isoflurane gas as well as the intramuscular injection of medetomidine hydrochloride (1.2–2.5 mg/kg; Kyoritsu Seiyaku Co., Japan) and butorphanol tartrate (0.8–1.7 mg/kg; Meiji Seika Pharma Co., Ltd., Japan), and the skin was shaved and swabbed with 70% ethanol and iodophors. The left kidney was subsequently exposed through a 1.5-cm lumbar incision. Eight hundred islets (size category: 101–200 µm in diameter) from the fresh control group, the NM vitrification group, or the SF vitrification group were transplanted into space beneath the kidney capsule of the diabetic rats using a glass capillary connected to a mouthpiece. The capsulotomy was left unsatured. The kidney was afterward placed back into its original position and the incision was closed with a surgical suture. The recipient rats were recovered from the anesthetic maintenance state by an intramuscular injection of atipamezole hydrochloride (6.0–12.5 mg/kg; Kyoritsu). The un-fasting blood glucose level, sampled by tail puncture, and the body weight gain of the recipient rats were monitored on Day-1, -4, -7, -14, -21, -28, -35, -42, -49, -56, -63, and -70 to assess the islet graft function. Rats that maintained a blood glucose level of < 200 mg/dl for two consecutive measurements were considered to have reversed diabetes (euglycemia). The left kidneys of the cured rats were removed on Day-70 under isoflurane anesthesia, and the blood glucose level as well as the body weight of the hemi-nephrectomized rats were monitored on Day-71, -74, and -77.
Recent developments in predicting CYP-independent metabolism
Published in Drug Metabolism Reviews, 2021
Nikhilesh V. Dhuria, Bianka Haro, Amit Kapadia, Khadjia A. Lobo, Bernice Matusow, Mary A. Schleiff, Christina Tantoy, Jasleen K. Sodhi
Atipamezole was demonstrated to more potently inhibit the major CYP isoforms than ABT with IC50 values less than 10 µM in all evaluations (with and without preincubation, in human, rat, and dog liver microsomes, and for all CYP isoforms) (Li et al. 2019c). The inhibitory potential of atipamezole was similar both with and without preincubation, indicating that atipamezole is a reversible CYP inhibitor and thus does not require preincubation in in vitro phenotyping assays. In contrast, the inhibitory potential of ABT varied greatly for each isoform with IC50 values with preincubation ranging from 2.7 to 460 µM in human liver microsomes, thus confirming results from previous studies (Emoto et al. 2003; Linder et al. 2009). Similar results were obtained for dog and rat liver microsomes. With respect to CYP2C9-mediated diclofenac metabolism, atipamezole potently inhibited the reaction with IC50 values of 1.8 µM and 1.5 µM with and without preincubation, respectively, whereas ABT resulted in less potent inhibition with IC50 values of 460 µM and 1083 µM, respectively. Next, it was confirmed in vivo in rats that both agents had the potential to inhibit diclofenac metabolism. Of note, it was also demonstrated that atipamezole does not inhibit P-glycloprotein (P-gp) in vitro and results were confirmed with rat pharmacokinetic studies using the P-gp substrate fexofenadine. In comparison, it has been previously reported that ABT also does not have inhibitory effects on P-gp nor on other clinically relevant xenobiotic transporters (Cheong et al. 2017).