• Archives of Pharmacal Research
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• 제29권11호
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• pp.977-983
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• 2006

The objective was to devise an animal model of myocardial infarction (MI) against which cardioprotective drugs might be tested. We describe the effects of nimesulide, a COX experience with development and validation of such a model. The rabbit was chosen in preference to rodents because its heart and cardiac circulation more closely resemble those of human. Thus, the cardiovascular system of anaesthetized male rabbits, 1 to 1.5 kg (n=11), was stressed by a single bolus intravenous injection of isoprenaline (ISP), 65 mg/kg. The effects of the injection were followed for sixteen days and were evaluated in four ways: 1) measurements of creatinine kinase isozyme and troponin-I (TPI) in serum 2) Electrocardiographic (ECG) changes (ST elevation and Q wave development) 3) Cardiac histopathology observed in tissue sections of the isolated of the heart. The histopathological analysis showed that rabbit heart on 2nd day after ISP injection showed changes of coagulation necrosis. Day 4 total coagulation with the loss of nuclear and striation associated with heavy interstitial infiltrate of neutrophils was found. Day 8 after infarction showed collagen deposition with capillary channels in between the remaining islands of myocytes in the infarcted area. On the 16th day scarring was complete. Coronary perfusion rates (CPR) and heart rate (HR) of the infarcted and nimesulide (a COX-2 inhibitor) treated rabbits displayed significant improvement (n=11) on each corresponding day after infarction as compared to the infarcted and saline treated rabbits (P<0.05). All four indices revealed similarities with effects commonly associated with MI in humans.

• Journal of Veterinary Science
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• 제25권3호
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• pp.36.1-36.15
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• 2024

Importance: The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is an attractive treatment option. On the other hand, it can result in severe complications, including pulmonary thromboembolism (PTE). Objective: The present study assessed the occurrence of PTE after the intravenous infusion of canine AdMSCs (cAdMSCs) into experimental animals. Methods: Five-week-old male BALB/c hairless mice were categorized into groups labeled A to G. In the control group (A), fluorescently stained 2×10⁶ cAdMSCs were diluted in 200 µL of suspension and injected into the tail vein as a single bolus. The remaining groups included the following: group B with 5×10⁶ cells, group C with 3×10⁶ cells, group D with 1×10⁶ cells, group E with 1×10⁶ cells injected twice with a one-day interval, group F with 2×10⁶ cells in 100 µL of suspension, and group G with 2×10⁶ cells in 300 µL of suspension. Results: Group D achieved a 100% survival rate, while none of the subjects in groups B and C survived (p = 0.002). Blood tests revealed a tendency for the D-dimer levels to increase as the cell dose increased (p = 0.006). The platelet count was higher in the low cell concentration groups and lower in the high cell concentration groups (p = 0.028). A histological examination revealed PTE in most deceased subjects (96.30%). Conclusions and Relevance: PTE was verified, and various variables were identified as potential contributing factors, including the cell dose, injection frequency, and suspension volume.

• Journal of Pharmaceutical Investigation
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• 제39권5호
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• pp.367-372
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• 2009

A rapid liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay method was developed for the determination of topotecan levels in rat serum. The assay utilized a single liquid-liquid extraction with a mixture of ethy l acetate and acetonitrile (6:1 v/v) and isocratic elution. The multiple reaction monitoring was based on the transition of m/z 422.0$\rightarrow$376.5 for topotecan and 315.1$\rightarrow$226.6 for clomipramine (internal standard). The developed assay was validated to demonstrate the specificity, recovery, lower limit of quantification (LLOQ), accuracy and precision. The assay was linear over a concentration range from 0.5-100 ng/mL, with LLOQ being 0.5 ng/mL using a small volume of rat serum (0.1 mL). The mean intra- and inter-day assay accuracy was 87.7-111.0% and 97.8-108.3, respectively, and the mean intra- and interday precision was between 1.6-4.3% and 3.8-10.3, respectively. The developed assay was applied to a pharmacokinetic study after a bolus i.v. injection of topotecan in rats.

• Archives of Plastic Surgery
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• 제44권5호
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• pp.361-369
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• 2017

As the popularity of fat grafting research increases, animal models are being used as the source of pre-clinical experimental information for discovery and to enhance techniques. To date, animal models used in this research have not been compared to provide a standardized model. We analyzed publications from 1968-2015 to compare published accounts of animal models in fat grafting research. Data collected included: species used, graft characteristics (donor tissue, recipient area, amount injected, injection technique), time of sacrifice and quantification methods. Mice were most commonly used (56% of studies), with the "athymic nude" strain utilized most frequently (44%). Autologous fat was the most common source of grafted tissue (52%). Subcutaneous dorsum was the most common recipient site (51%). On average, $0.80{\pm}0.60mL$ of fat was grafted. A single bolus technique was used in 57% of studies. Fat volume assessment was typically completed at the end of the study, occurring at less than 1 week to one year. Graft volume was quantified by weight (63%), usually in conjunction with another analysis. The results demonstrate the current heterogeneity of animal models in this research. We propose that the research community reach a consensus to allow better comparison of techniques and results. One example is the model used in our laboratory and others; this model is described in detail. Eventually, larger animal models may better translate to the human condition but, given increased financial costs and animal facility capability, should be explored when data obtained from small animal studies is exhausted or inconclusive.

• Journal of Chest Surgery
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• 제57권3호
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• pp.291-299
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• 2024

Background: Postoperative pain management following minimally invasive repair of pectus excavatum (MIRPE) remains a critical concern due to severe post-procedural pain. Promising results have been reported for cryoanalgesia following MIRPE; however, its invasiveness, single-lung ventilation, and additional instrumentation requirements remain obstacles. Serratus anterior plane block (SAPB) is a regional block technique capable of covering the anterior chest wall at the T2-9 levels, which are affected by MIRPE. We hypothesized that SAPB would be a superior alternative pain control modality that reduces postoperative pain more effectively than conventional methods. Methods: We conducted a retrospective study of patients who underwent MIRPE between March 2022 and August 2023. The efficacy of pain control was compared between group N (conventional pain management, n=24) and group S (SAPB, n=26). Group N received intravenous patient-controlled analgesia (IV-PCA) and subcutaneous local anesthetic infusion. Group S received bilateral continuous SAPB with 0.3% ropivacaine after a bilateral bolus injection of 30 mL of 0.25% ropivacaine with baseline IV-PCA. Pain levels were evaluated using a Visual Analog Scale (VAS) at 1, 3, 6, 12, 24, 48, and 72 hours postoperatively and total intravenous rescue analgesic consumption by morphine milligram equivalents (MME). Results: Mean VAS scores were significantly lower in group S than in group N throughout the 72-hour postoperative period (p<0.01). Group S showed significantly lower MME at postoperative 72 hours (group N: 108.53, group S: 16.61; p<0.01). Conclusion: SAPB improved immediate postoperative pain control in both the resting and dynamic states and reduced opioid consumption compared to conventional management.

• The Korean Journal of Pain
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• 제4권2호
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• pp.127-132
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• 1991

Recently a non-electronic, disposable and portable infusor(Baxter infusor with patient control module, Baxter health care Co., Deerfield IL 60015 USA: BI $\bar{c}$ PCM) has been developed that will deliver both a continuous drug infusion as well as allow the patient to deliver extra doses of medication on a demand basis under predetermined limitation of analgesics. Patients may also not require as high analgesic dose rate to control pain when the acceptable and tolerable level of pain relief can be maintained by this device. From April l99l, we have used a total l93 units of BI $\bar{c}$ PCM. These units consisting of two components which one made by a balloon reservoir(capacity 65 ml, flow rate 0.5 ml/hr) to store medication and to regulate the pump power(490 torr), and another two PCMs to regulate additional analgesic administration by patients demand at intervals of 1S minutes and 60 minutes. The dose administered to the patient can be varied by changing the concentration of the infusate within the balloon reservoir. These devices were utilized for the pain control of 44 patients. These patients were divided into two groups. Twenty seven cases had cancer pain and 17 cases had non-cancer pain. The Touhy needle(No. l8 G.) tip was inserted into the epidural space and was used to guide the catheter to the spinal nerve level corresponding to the most painful area. The device was connected to the opposite site of the catheter tip and was filled with 60 ml of mixture solution such as 0.5% bupivacaine 15 ml, morphine HCl 10 mg, trazodone 10 ml, Tridol 3 ml and normal saline 31 ml were administed as the initial dose. When the initial dose was less effective, the next dose could be varied by increasing the concentration of bupivacaine, by adding more morphine (5~10 mg), and by reducing the volume of normal saline. Using these modules of drug self administration, we experienced the following: 1) Improvement of patient's self titration of analgesic requirement was provided. 2) The patients anxiety with pain recurrence resulting from delays in administering pain control medication was decreased significantly. 3) The working load accompanying with the single bolus injection as the usual method was reduced remarkably. 4) There was urinary retention in 5 cases and pruritus in 4 eases which developed as side effects but respiratory depression and vomiting was not encountered in a single case.

• Biomolecules & Therapeutics
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• 제5권1호
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• pp.100-105
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• 1997

DW-166HC ($^{166}$Holmium-chitosan) is a complex of $^{166}$Ho, $\beta$- and $\gamma$-ray emitter, and chitosan, a polymer of glucosamine, with radiotherapeutic potential. The current study was performed to determine the acute toxicities of $^{165}$Ho-chitosan in mice by two different routes of administration. The both sex mice were given a single intravenous bolus injection of $^{165}$Ho-chitosan complex at doses of 12, 10, 6, 5 and 4 mg/kg or subcutaneous administration at doses of 600, 500, 400 and 300 mg/kg. Chitosan was dosed to control animals as 16 and 800 mg/kg, intravenously and subcutaneously, respectively. The doses of $_{165}$Ho-chitosan complex were expressed as $_{165}$holmium nitrate pentahydrate and the ratio of $^{165}$Ho$(NO_3)_3$).$5H_2O$ to chitosan was 3/4 Severe convulsion and respiratory failure were followed by death within 10 min after intravenous dosing. Transient unilateral hindlimb hypokinesias were found in two mice of 5 mg/kg dosing group during the study period. No abnormalities were observed during the necropsy of survived animals in intravenous dosing group. Only one male animal was found dead in 500 mg/kg subcutaneously dosed group. Alopecia with or without cutaneous ulcer were found in most mice including control animals. During necropsy, omental adhesion was observed in all dose ranges and enlarged spleen was found in several animals including control group. It is suggested that the acute intravenous >).$LD_{50}s$ for male and female mice were 4.90 and 6.03 mg/kg, respectively. The lowest lethal dose in male was 500 mg/kg by subcutaneous administration.

• 대한방사선기술학회지:방사선기술과학
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• 제26권3호
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• pp.33-39
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• 2003

잡견의 간흡충증에서 조영기법의 역동적 CT 영상과 MIP 기법을 적용한 자기공명 영상의 질을 비교하여 임상적 적용 가능성을 알아보고자 하였다. 20마리의 잡견(평균 20kg)에 실험적으로 간흡충증을 유발한 후 13주 동안에 간을 중심으로 CT 영상과 MR 영상을 얻었다. CT는 이중나선식방법으로 영상을 획득하였고, bolustracking 방법으로 조영제를 주입하여 arterial phase는 5초 후에 정맥기는 동맥기 scan후 15초에 시작하여 single dynamic scan을 하고, 데이터를 다 단면 영상을 얻기 위해 MnP로 재구성을 하였다. MR 영상은 circularly polarized phased away body coil을 사용하였고, HASTE, FLASH, TSE 기법을 이용하여 모두 2차원 영상을 얻었다. HASTE와 TSE는 해상력을 증가시키기 위하여 interpolation과 지방소거기법을 적용하였다. 데이터를 획득하는 방식으로는 담관을 중심으로 3방향으로 수집한 다음 최대강도투사법으로 재구성하였다. CT와 MR 영상의 평가 방법으로서는 간내담관의 확장, 동맥기에 담관벽의 조영증강, 담관 말단부의 확장, 간의 실질조직묘사, 배경유무를 기점으로 병리학과 의사 1명과 방사선과 의사 3명, 방사선사 5명이 시각적으로 평가를 하였다. MR 영상의 경우 sequence 비교를 위해 정량적분석방법인 CNR과 CR로 평가를 하였다. 감염 후 5마리의 잡견은 죽었으며, 15마리 잡견에서 CT와 MR 검사에서 간내 담관의 만성 확장을 보여 주었다. 조영증강기법인 CT 영상에서는 간 실질조직을 비롯하여 담관벽의 조영증강이 보였고, MR 영상에서는 간내담관 형태와 담관의 말단부의 확장이 MIP 기법을 이용하여 3차원적으로 관찰되었고, CNR과 CR 값이 HASTE($16{\pm}0.83$, 73.3%), TSE($7.06{\pm}3.0$, 62.3%), FLASH($1.19{\pm}0.2$, 6.4%) 순으로 나타났다. CT와 MR 영상은 짧은 검사기법과 다양한 검사기법을 포함하고 있어 간흡충증을 영상화하는데 있어서 진단적 가치가 있다. CT와 MR 영상 검사의 장 단점을 서로 보안하여 검사를 시행한다면 높은 임상적 적용 가능성이 있다.