• Toxicological Research
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• v.16 no.3
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• pp.211-219
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• 2000

The therapeutic effect of AS2-006A, a derivative of asiaticoside, has been studied and is being developed as a new wound-healing agent. In the present study, the general pharmacological effects on 1) central nervous system, 2) autonomic nervous system, 3) respiratory system, 4) gastrointestinal system. 5) cardiovascular system. and 6) urinary system were assessed in experimental animals and in in vitro models. 1. In vivo animal study: External applications of the 1 % gel ointment of AS2-006A to rats at the doses of 200. 600 or 2000 mg/kg body weight showed no observable pharmacological effects. The effects on the central nervous system were assessed by observation of behavior, hexobarbital-induced sleeping time, pentetrazole-induced convulsion assay, body temperature measurements, and observations on spontaneous activity and catalepsy. The gel ointment exhibited no effects on the cardiovascular system (i.e. blood pressure and heart rate), renal physiology (i.e. urine volume and electrolytes excretion) and gas-trointestinal physiology (i.e. intestinal charcoal propulsion and gastric mucosal irritation). 2. In vitro experiments: The effects of AS2-006A on the physiology of smooth and cardiac muscles were assessed. Muscle contractions were isotonically and isometrically measured in organ chambers using a physiograph. Cumulative additions of AS2-006A (10$^{-9}$ -10$^{-5}$ M) induced no changes in the tension of isolated guinea pig ileum and tracheal muscles. AS2-006A only slightly increased contractility of rat atrial and papillary muscles at 10$^{-2}$ M, which was not statistically different from control. These data showed that the gel ointment of AS2-006A could be externally applied as a wound-healing agent with no potential side effects.

• Korean Journal of Veterinary Research
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• v.47 no.1
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• pp.103-115
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• 2007

The aim of this study was to compare the reaction of the cardiovascular system, and the anesthetic effect among 3 experimental groups, epidural administration of medetomidine as a single agent, the combination of buprenorphine and medetomidine, and the combination of fentanyl and medetomidine. Twenty one dogs were anesthetized with isoflurane and allowed to breathe spontaneously. Epidural, arterial, and venous catheters were inserted. The tip of epidural catheter was positioned at the level of the space between the sixth and seventh lumbar vertebra. After a stable plane of anesthesia was achieved, these dogs were each administered one of the following treatments epidurally : medetomidine $10{\mu}g/kg$ (Group M), a combination of medetomidine $5{\mu}g/kg$ and buprenorphine $10{\mu}g/kg$ (Group M/B), and a combination of medetomidine $5{\mu}g/kg$ and fentanyl $10{\mu}g/kg$ (Group M/F). Heart rate (HR), Respiratory rate (RR), End-tidal carbon dioxide (EtCO2), and arterial blood pressure were measured before drug administration (base line) and 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 min postinjection. Blood gas analysis was performed before injection and 5, 15, 25, 35, 45, 60 min postinjection. Isoflurane was discontinued 80 min postinjection and pain/motor function were evaluated up to 260 min postinjection every 15 min. At the early stage of drug introduction (until 5 min), the HR was decreased significantly in all 3 groups compared with base line. In Group M, HR was significantly decreased compared with the other 2 groups. With time (starting 20 min after drug introduction), the HR was decreased significantly in Group M/B in respect to base line. However, no significant difference was seen number-wise in all 3 groups. During 60 min after drug introduction, the systolic, diastolic and mean arterial pressures were highest in Group M and lowest in Group M/F. Among 3 groups, drug action and motor loss duration were longest in Group M/F. Analgesic effect observed in the M/F group was the most prominent and long-lasting, compared to those seen in the other 2 groups. Given the fact that the recovery of motor function takes place in a short period of time after analgesic effects disappeared, additional use of M/F depending on the patient's condition would be a good way to achieve effective pain management. However, proper care should be taken to ensure the function of cardiovascular system in the patient because the administration of M/F under isoflurane anesthesia results in a significant decline in arterial blood pressure ($65{\pm}10mmHg$).

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.261-269
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• 1995

Background; To explore the efficacy of aspartate as NAD regenerating agent for ethanol and acetaldehyde oxidation, we performed crossover challenge in two groups of volunteers by coadministration of various doses of aspartate, asparagine and ethanol. Methods; 18 healthy male volunteers were randomly divided into two groups. 6 volunteers of the first group were administered 5 gm monosodium aspartate(MSA), 5 gm asparagine or placebo with 100 ml of $40^{\circ}$ whiskey by the 3 way-crossover design, while 12 volunteers of the other group were administered placebo, 1, 2 or 5 bottles of $Aspar^(circledR)$ containing 1 gm of MSA per bottle with 100 ml of $40^{\circ}$ whiskey by the 4 way-crossover design. Ethanol(and acetaldehyde) concentrations in venous blood drawn at 0, 0.25, 0.5, 1, 2, 4, 8th hour after ethanol ingestion were analysed by gas chromatogaphy. Subjective symptoms, liver function tests and psychomotor function tests were also performed during the study periods. Result; Plasma concentration and AUC of acetaldehyde in asparagine and MSA trials on ethanol ingestion were significantly lower than those of placebo trial in the 1st group. Plasma ethanol concentration of 5 bottle $Aspar^(circledR)$ trial was significantly lower than that of placebo trial in the 2nd group. Improvement of subjective symptoms or psychomotor performance by the treatment was not statistically significant. Conclusion; Aspartate and asparagine may be prospective candidates for acceleration of ethanol metabolism and prevention of ethanol toxicity.

• Journal of The Korean Society of Clinical Toxicology
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• v.16 no.2
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• pp.157-160
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• 2018

Chronic silica nephropathy has been associated with tubulointerstitial disease, immune-mediated multisystem disease, chronic kidney disease, and end-stage renal disease. On the other hand, acute intentional exposure is extremely rare. The authors' experienced a 44-year-old man who took rapid cement hardener (sodium silicate) in a suicide attempt whilst in a drunken state. He visited the emergency department approximately 1 hour after ingestion. Information on the material was obtained after 3 L gastric lavage. The patient complained of a sore throat, epigastric pain, and swollen to blood tinged vomitus. Proton pump inhibitors, hemostats, steroid, and fluids were administered. Nine hours after ingestion, he was administered 200 mL hematochezia. Immediately after, a gas-troenterologist performed an endoscopic procedure that revealed diffuse hyperemic mucosa with a color change and variable sized ulceration in the esophagus, whole stomach, and duodenal $2^{nd}$ portion. Approximately 35 hours later, persistent oligouria and progressive worsening of the renal function parameters (BUN/Cr from 12.2/1.2 to 67.5/6.6 mg/dL) occurred requiring hemodialysis. The patient underwent 8 sessions of hemodialysis for 1 month and the BUN/Cr level increased to 143.2/11.2 mg/dL and decreased to 7.6/1.5 mg/dL. He was discharged safely from the hospital. Follow up endoscopy revealed a severe esophageal stricture and he underwent endoscopic bougie dilatation. Acute cement hardener (sodium silicate) intoxication can cause renal failure and strong caustic mucosal injury. Therefore, it is important to consider early hemodialysis and treatment to prevent gastrointestinal injury and remote esophageal stricture.

• Journal of Veterinary Clinics
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• v.36 no.6
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• pp.306-313
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• 2019

It is important to identify the most suitable anesthetic agent that has minimal side effects to be able to control and perform surgeries on bears. In this study, we examined and compared the induction and recovery times as well as the physiological changes occurring during anesthesia induced by medetomidine-zolazepam/tiletamine (MZT) and xylazine-zolazepam/tiletamine (XZT) at general anesthesia for laparoscopic salpingectomy in 326 female Asiatic black bears. The body temperature, heart rate, respiratory rate, and levels of PaO₂ and EtCO₂ were the physiological changes measured during surgical procedures in female bears after anesthesia. In addition, the levels of pO₂, pCO₂, and sO₂ were measured using a portable blood gas analyzer. To induce recovery from anesthesia, bears anesthetized with MZT were intravenously administered atipamezole and bears anesthetized with XZT were intravenously administered yohimbine. The combination MZT, at dosages of 0.019 ± 0.001 mg/kg for medetomidine and 1.4 ± 0.1 mg/kg for ZT, or the combination XZT, at dosages of 2.0 ± 0.1 mg/kg for xylazine and 3.0 ± 0.1 mg/kg for ZT, proved to be reliable and effective in anesthetizing Asiatic black bears for a 40-min handling period for routine clinical procedures. The average anesthesia induction times were 16.5 ± 0.95 min for the bears in the MZT group and 12.0 ± 0.44 min for those in the XZT group. A significant difference was noted between the two drugs (P < 0.001) in terms of the average anesthesia induction time. The anesthesia induction time was shorter for bears with lower body weights than those with higher body weights (P < 0.05). The recovery time of MZT was significantly faster than that of XZT (11.3 ± 0.45 min vs. 18.5 ± 0.83 min) (P < .001). The bears anesthetized with MZT exhibited lower cardiopulmonary suppression than those anesthetized with XZT (P < 0.05). The body temperatures and EtCO₂ of bears in the M ZT group were significantly lower than those in the XZT group as time progressed after anesthesia (P < 0.05). The average pO₂ before the bears were supplied with oxygen was 64.8 ± 3.7 mmHg, but it increased to 211.5 ± 42.5 mmHg afterwards (P < 0.001). In conclusion, our results indicate that bears anesthetized with MZT have longer anesthesia induction time, shorter recovery time, slower heart and respiratory rates, and lower body temperatures and EtCO₂ than those anesthetized with XZT. These findings suggest that XZT is preferable to MZT, warranting further research on its uses and clinical responses in bears.