In order to establish optimal dosage schedules and withdrawal times for sulfamethazine(SMZ) in pigs, pharmacokinetic and tissue distribution experiments were conducted in pigs. For comparative purposes, tissue depletion kinetics are also studied in rats. From three pigs administered with SMZ i.v., the pharmacokinetic profile of SMZ in two pigs was adequately described by a one-compartment open model whereas that in one pig was patterned after a two-compartment open model. Volume of distribution(Vd) was 0.48~0.57 L/kg and biological half-life($t_{1/2}$) was 11.8-16.8 h. From three pigs dosed with SMZ p.o., pharmacokinetic profile was explainable with a one-compartment open model. Time to reach maximum SMZ concentration in serum (Tmax) was 2.8 h, 3.2 h and 7.5 h. Elimination half-life was 2.8-7.5 h. The descending order in concentration of SMZ was plsama > kidney > liver > lung > heart > pancreas > spleen > duodenum > ileum > brain > adipsoe tissue from three pigs sacrificed at 5h, 29h and 54h after the administration of SMZ, p.o.. The protein binding of SMZ in pigs was 55.2%($2.5{\mu}g/ml$), 71.5% ($5{\mu}g/kg$) and 71.5%($10{\mu}g/ml$). The mean systemic bioavailability (F) of SMZ p.o. was 49.1 %. Meanwhile the pharmacokinetic profile of SMZ in rats was adequately described by a one-compartment open model. Absorption of SMZ p.o. in the rat was very rapid. In conclusion, the oral optimal dosage regimen of SMZ for pigs was the initial dose of 45.7 mg/kg followed by the maintenance dose of 30.2 mg/kg for high specific pathogens to SMZ. The time to reach below the stipulated residual allowable concentration (0.1 ppm) was calculated 93 h after oral administration of 200 mg/kg recommended by manufactureres.
Changes of plasma DNA contents and serum biochemical values were measured in rats administered with $HgCl_2$ to investigate the in vivo cytotoxic effects of mercury and examine the usefulness of these changes as indicators of mercury exposure and diagnosis of mercury poisoning. Rats were given once intraperitonealy $HgCl_2$(0.13. 0.32. 0.8 and 2 mg/kg b.w) and the changes of plasma DNA contents and serum biochemical values were measured at the time of 2, 4, 8, 24, 48 and 72 hours after the administration of $HgCl_2$. Plasma DNA contents began to increase from 2 hours after the administration of $HgCl_2$ in all the treatment groups significantly compared to control with dose-dependent pattern. The levels of plasma DNA reached to peak at 48 hours as 2.77, 7.60, 15.46 and 16.51 times higher than control in each treatment group of 0.13, 0.32, 0.8 and 2 mg/kgb.w, respectively and remained to be higher until 72 hours after the administration. The values of creatine kinase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, blood urea nitrogen and glucose of serum were increased, however the values of alkaline phosphatase, total protein and triglyceride were decreased. These changes of increase and decrease showed dose-dependent pattern but the starting time, maintenance and magnitude of change were various and characteristic according to serum biochemical indices. Among the changes of serum biochemical values, those of aspartate aminotransferase, lactate dehydrogenase and blood urea nitrogen were apparently and significantly increased compared to control from 2 to 72 hours by the administration of 2 mg/kg $HgCl_2$. This study demonstrates that plasma DNA and serum biochemical values such as aspartate aminotransferase, lactate dehydrogenase, blood urea nitrogen and etc. are valuable as biomarkers for mercury exposure assessment and diagnosis of mercury poisoning.
Tai, Cheng-Jeng;Pan, Chin-Kwun;Chen, Ching-Shyang;Hung, Chin-Sheng;Wu, Chih-Hsiung;Chiou, Hung-Yi
Asian Pacific Journal of Cancer Prevention
/
v.14
no.3
/
pp.1981-1984
/
2013
Objective: The optimal duration of adjuvant trastuzumab treatment in patients with HER2-positive breast cancer is not known. The aim of this study was to evaluate the efficacy of 6 months of adjuvant trastuzumab treatment in patients with stage II or III HER2-positive breast cancer. Methods: The records of patients with HER2-positive stage II or III breast cancer who were admitted to the Breast Center of Taipei Medical University Hospital and Yuan's General Hospital between 2000 and 2008 were reviewed. All patients received adjuvant trastuzumab at an initial dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg/week for 22 weeks in combination with chemotherapy. Results: A total of 51 patients were included with a mean age of 46.9 years. Approximately 55% of the patients had stage III disease. The mean follow-up time from initiation of treatment was 45.2 months (range, 0.9 to 85 months). During follow-up, 46 patients (90.2%) did not experience tumor recurrence. The mean estimated disease free survival was 80.2 months. The estimated 1-, 2-, 5-, and 7-year survival rates were 97.9%, 93.1%, 93.1%, and 93.1%, respectively. The most common adverse effects were gastrointestinal symptoms (21.6%), chills (17.6%), dizziness (9.8%), and bone pain (7.8%). No cardiac or hematologic adverse events occurred. Conclusion: Adjuvant therapy with trastuzumab for 6 months resulted in a clinical benefit in patients with HER2-positive breast cancer.
Purpose: The purpose of this study is to identify the changes of a physiologic nature and the sedative parameters associated with dexmedetomidine and pethidine, in patients undergoing plate and screw removal surgery, after orthognathic surgery. Methods: Twenty-three patients were sedated with dexmedetomidine and pethidine during plate and screw removal, after orthognathic surgery. An initial loading dose of dexmedetomidine ($1.0{\mu}g/kg$ infused over 10 minutes) was followed by a maintenance dose ($1.0{\mu}g/kg/hr$). Systolic blood pressure, diastolic blood pressure, mean arterial pressure, oxygen saturation, and heart rate were monitored. Perioperative amnesia and anxiety were recorded. Results: Significant changes were found in the blood pressure and heart rate (Freidman test, P<0.05), but not in oxygen saturation (Freidman test, P>0.05). Amnesia during local injection was observed in eight patients (34.8%). Compared with the preoperative anxiety score, the intraoperative anxiety score was decreased. Conclusion: In this study, we found cardiovascular and respiratory stability in intravenous sedation using dexmedetomidine with pethidine, in plate and screw removal, after orthognathic surgery. Furthemore, intravenous sedation using dexmedetomidine with pethidine shows adequate analgesic and sedative effects.
Shin, Jae Won;Jung, Yun Seob;Park, Kyungsoo;Lee, Soon Min;Eun, Ho Seon;Park, Min Soo;Park, Kook In;Namgung, Ran
Clinical and Experimental Pediatrics
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v.60
no.2
/
pp.50-54
/
2017
Purpose: The aims of this study were to evaluate the safety and pharmacokinetics of levetiracetam (LEV) in neonates with seizures and to establish a population pharmacokinetics (PPK) model by using the software NONMEM. Methods: A retrospective analysis of 18 neonatal patients with seizures, who were treated with LEV, including 151 serum samples, was performed. The mean loading dose was 20 mg/kg, followed by a mean maintenance dose of 29 mg/kg/day. Results: Seventeen neonates (94%) had seizure cessation within 1 week and 16 (84%) remained seizure-free at 30 days under the LEV therapy. The mean serum concentration of LEV was $8.7{\mu}g/mL$. Eight samples (5%) were found above the therapeutic range. No serious adverse effects were detected. In the PPK analysis for Korean neonates, the half-life was 9.6 hours; clearance, 0.357 L/hr; and volume of distribution, 4.947 L, showing differences from those in adults. Conclusion: LEV is a safe and effective option for the treatment of neonatal seizures with careful therapeutic drug monitoring.
Journal of the korean academy of Pediatric Dentistry
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v.23
no.3
/
pp.717-728
/
1996
The effects of electro-acupuncture on the pain threshold and the amplitude of dEMG(di-gastric EMG) evoked by the noxious electric stimulation on teeth and gingiva in dogs were studied. Experiments were carried out with 10 dogs weighing 5-8kg. Each animal was anestheticed with Entobar given intraperitoneally in an initial dose of 30mg/kg. Maintenance dose of 5mg/kg/hr was given through a cannula, in the femoral vein, as required to keep up light anesthesia. Bipolar stimulating wire electrodes, 0.1mm in diameter, insulated except for tips, were inserted into the upper canine and palatal gingiva. Rectangular aluminium plate electrodes (15$\times$5mm) were placed on acupuncture points, called Yin-Hsiang, located at both sides of the upper jaw. Rectangular biphasic current pulses of 2Hz, with a $250{\mu}sec$ duration, were delivered for 15 minutes. The dEMG activities were recorded from the anterior belly of the digastric muscle(one of the jaw opening muscles) using bipolar wire electrodes. The magnitude of the jaw opening reflex at different intensties of electro-acupuncture(1volt 4volt and 10volt) was estimated by averaging the 30 superimposed dEMGs recorded on an oscilloscope and audiomonitor. Data were analysed statistically with ANOV A and paired t-test. The obtained results were as follows: 1. Pain thresholds were increased 7.7 %, 15.4 %, 17.3 % in the teeth and 11.1 %, 19.0 %, 25.4 % in the gingiva as the intensities of electro-acupuncture increased incrementally. 2. Amplitudes of dEMG were decreaed 8.3%, 22.4%, 27.4% in the teeth and 9.8%, 36.5%, 42.2 % in the gingiva as the intensities of electro-acupuncture increased incrementally. 3. Inhibition of pain responses by the electroacupuncture was more effective in the gingiva than in the teeth.
Proceedings of the Korean Radioactive Waste Society Conference
/
2003.11a
/
pp.90-95
/
2003
Chemical management of annulus gas system is carried out for the purpose of ensuring the safety and reliability of the system via securing the integrity of the system, detecting the D$_2$O in-leakage of coolant and/or moderator, and reducing the radiation dose. Since the quality of CO_2$ gas, which is used as a filling gas for annulus gas system at CANDU plants, has a propound effect on the integrity of the system material and the radiation dose, CO_2$ gas of high quality is needed. If the quality of CO_2$ gas does not meet the specification, it may give rise to undesirable effect not only on the annulus gas system, but also on the environment due to the production of radioactive nuclei. Therefore, it is very important to check the impurities of CO_2$ gas. Based on this background, the inventories of C-14 and Ar-41 in CO_2$ gas that is supplied as annulus gas were estimated using the data on concentrations of the impurities of $CO_2$ such as C, N_2$ and Ar. The results of this study is expect to give useful information on optimization of CO_2$ impurities maintenance and management of gaseous radioactive wastes produced at CANDU plants.
Journal of The Korean Society of Clinical Toxicology
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v.20
no.2
/
pp.39-44
/
2022
N-Acetylcysteine (NAC) is the standard antidote treatment for preventing hepatotoxicity caused by acetaminophen (AAP) poisoning. This review summarizes the recent evidence for the treatment of AAP poisoning. Several alternative intravenous regimens of NAC have been suggested to improve patient safety by reducing adverse drug reactions and medication errors. A two-bag NAC infusion regimen (200 mg/kg over 4 h, followed by 100 mg/kg over 16 h) is reported to have similar efficacy with significantly reduced adverse reactions compared to the traditional 3-bag regimen. Massive AAP poisoning due to high concentrations (more than 300-lines in the nomogram) needs to be managed with an increased maintenance dose of NAC. In addition to NAC, the combination therapy of hemodialysis and fomepizole is advocated for severe AAP poisoning cases. In the case of a patient presenting with an altered mental status, metabolic acidosis, elevated lactate, and an AAP concentration greater than 900 mg/L, hemodialysis is recommended even if NAC is used. Fomepizole decreases the generation of toxic metabolites by inhibiting CYP2E1 and may be considered an off-label use by experienced clinicians. Since the nomogram cannot be applied to sustained-release AAP formulations, all potentially toxic sustained-release AAP overdoses should receive a full course of NAC regimen. In case of ingesting less than the toxic dose, the AAP concentration is tested twice at an interval of 4 h or more; NAC should be administered if either value is above the 150-line of the nomogram.
Superovulation with exogenous gonadotropins creates a spectrum of pre or periovulatory hormonal changes with subsequent detrimental effects on oocyte quality, fertilization, embryo development, implantation and maintenance of pregnancy. Our recent study determined potential roles for insulin-like growth factor-1 (IGF-1) in uterine environment regulation and preimplant tation in the rat. The evidence indicates that IGF-l may play an important role in the main tenance of a receptive uterine environment for embryonic development and the regulation of decidualization. Embryonic loss and failure of implantations following superovulation may be partially attributed to disturbances in uterine IGF-l action as observed in this study. We investigated the effects of superovulatory doses of gonadotropins on frequency of chromosomal a abnormalities of mouse embryos. Chromosome a analysis of mouse zygotes and 8- to 16-cell stage embryos from spontaneously ovulated, 5, 10, and l 15 lU pregnant mare serum gonadotropin (PMSG) superovulated mice was carried out. Aneuploidy, polyploidy and structural chrom- osomal abnormalities were detected among the four groups. However, only polyploidy was correlated with superovulation. In 10 and 15 IV PMSG treated groups, the rate of polypoidy was 2.9% and 10.5%, respectively. Furthermore, there was a dose reponse relationship between the PMSG dose and the incidence of embryonic p polyploidy (P
Purpose: The long-term efficacy and safety of infliximab (IFX) in children with ulcerative colitis (UC) have not been well-evaluated. Here, we reviewed the long-term durability and safety of IFX in our single center pediatric cohort with UC. Methods: This retrospective study included 20 children with UC who were administered IFX. Results: For induction, 5 mg/kg IFX was administered at weeks 0, 2, and 6, followed by every 8 weeks for maintenance. The dose and interval of IFX were adjusted depending on clinical decisions. Corticosteroid (CS)-free remission without dose escalation (DE) occurred in 30% and 25% of patients at weeks 30 and 54, respectively. Patients who achieved CS-free remission without DE at week 30 sustained long-term IFX treatment without colectomy. However, one-third of the patients discontinued IFX treatment because of a primary nonresponse, and one-third experienced secondary loss of response (sLOR). IFX durability was higher in patients administered IFX plus azathioprine for >6 months. Four of five patients with very early onset UC had a primary nonresponse. Infusion reactions (IRs) occurred in 10 patients, resulting in discontinuation of IFX in four of these patients. No severe opportunistic infections occurred, except in one patient who developed acute focal bacterial nephritis. Three patients developed psoriasis-like lesions. Conclusion: IFX is relatively safe and effective for children with UC. Clinical remission at week 30 was associated with long-term durability of colectomy-free IFX treatment. However, approximately two-thirds of the patients were unable to continue IFX therapy because of primary nonresponse, sLOR, IRs, and other side effects.
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