• Clinical and Experimental Pediatrics
• /
• v.61 no.11
• /
• pp.355-361
• /
• 2018

Purpose: Headache is a common symptom during childhood. It is usually persistent and requires special care. This study aimed to identify the characteristics of headache in children <7 years of age. Methods: We reviewed 3 years of clinical files on children <7 years of age with a chief complaint of headache. Results: This study included 146 children (66 males, 80 females; mean age, $5.5{\pm}1.0years$). Mean symptom duration was $5.8{\pm}7.9months$. Attack durations were longer than 2 hours in 31 patients, shorter than 2 hours in 70 patients, and unchecked in 45 patients. Attack frequency was $15.1{\pm}10.6$ times per month. Pain locations and characteristics were also variable. Mean pain severity score was $5.1{\pm}2.2$ on the visual analog scale. Of 38 patients who underwent electroencephalography, 9 showed positive findings. Of 41 who underwent brain magnetic resonance imaging, 20 showed positive findings. The diagnoses were migraine (including probable migraine) in 34, tension-type headache in 5, and congenital malformations in 3. Medications were used in 29 patients: acetaminophen in 17, ibuprofen in 8, naproxen sodium in 1, and topiramate or amitriptyline in 3. Conclusion: In children aged <7 years, headache has a relatively benign course, but detailed history taking is needed for more accurate diagnosis.

• Biomolecules & Therapeutics
• /
• v.3 no.1
• /
• pp.85-90
• /
• 1995

Phenol, acetaminophen (AA) and salicylamide are all known to be sulfated in rats and mice. We have previously demonstrated that capacity-limited sulfation of xenobiotics in rats is due to the reduced availability of hepatic 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the cosubstrate for sulfation, which in turn is limited by the availability of its precursor, inorganic sulfate. Because species differences have been reported in the extent of sulfation, this study was conducted to determine whether these xenobiotics lower hepatic PAPS and sulfate in ICR mice. All three substrates decreased serum sulfate concentrations in a dose- and time-dependent manner. However, contrary to the observations in rats, phenol markedly increased hepatic PAPS concentrations in a dose-dependent manner, 1 hr after ip injection of 0∼4 mmol/kg. Following ip injection of 4 mmol/kg phenol, hepatic PAPS concentraions were enhanced 2∼3 fold, 0.5-2 hr after dosing and returned to control values 3 hr after dosing, whereas AA and salicylamide had little effect on hepatic PAPS concentraions. In summary, these studies demonstrate that phenol markedly enhances hepatic PAPS concentrations in mice, whereas hepatic PAPS levels are not affected by AA and salicylamide. Our data suggest that 1) hepatic sulfation for high dosages of xenobiotics in ICR mice is not limited by the availability of cosubstrate and 2) there are significant species differences in the regulation of PAPS between rats and mice.

• Biomolecules & Therapeutics
• /
• v.5 no.2
• /
• pp.117-124
• /
• 1997

The analgesic effects of DA-5018, a new caosaucin derivative, were evaluated in various experimental pain models. Drugs were administered subcutaneously or topically. When drugs were administered subcutaneously, 1) the $ED_{50}$ of DA-5018, morphine . HCI, capsaicin and acetaminophen were 0.091-2.0, 0.3-4.3, 1.4-26.5 and 45.4-643 mg/kg, respectively in various pain or inflammatory models including acetic acid writhing, formalin, tail flick, Randall-Selitto, hot plate and crouton oil-induced ear edema test, 2) the AD2 values (the dose for doubling of pain threshold of vehicle control) of DA-5018, capsaicin and ketoprpgin were 1.07 $\pm$ 0. 18, 23.47$\pm$4.46 and 2.97$\pm$0.43 mg/kg in Freund's complete adjuvant (FCA)-induced arthritic pain model. And by topical application, 1) neither DA-5018 0.3% cream nor Zostrix-HP (capsaicin 0.075%) were effective in formalin test, 2) although DA-5018 0.3% cream significantly inhibited the croton oil-induced ear edema being better than Zostrix-HP and Kenofen (ketoprofen 3%). 3) In FCA model, DA-5018 0.3% cream reversed the decreased pain threshold of arthritic rat from 136.4 g (day 0) to 289.0 g (day 5) and 250.1 g (day 10), which was similar to Zostrix-HP. These results suggest that DA-5018 administered subcutaneously has a potent and broad analgesic spectrum than nonsteroidal antiinflammatory drugs against acute and chronic pain, and by topical application it exerts comparable analgesic and antiinglammaatory effects to capsaicin cream.

• Journal of Pharmaceutical Investigation
• /
• v.32 no.4
• /
• pp.313-319
• /
• 2002

Rat skin permeation of various nonsteroidal antiinflammatory drugs (NSAIDs) was investigated in vitro using Franz diffusion cell at $37^{\circ}C$. The effect of various skin permeation enhancers was also observed as a preliminary study of developing transdermal delivery systems of NSAIDs. Lipophilicity of NSAIDs was determined from thε partition coefficient (log P) in 1-octanol/water and 1-octanol/IPB mutual-saturated solutions. The solubility was determined in water, isotonic phosphate buffer (IPB), and propylene glycol (PG) at $37^{\circ}C$. The rat skin permeation rate of acetaminophen, piroxicam, and aceclofenac was almost negligible, although they were saturated in PG. Addition of 1 % permeation enhancer increased the permeation rate of ketoprofen, ketorolac, and diclofenac. However, the skin permeation rate of ibuprofen did not increase with the addition of various enhancers. Among the permeation enhancers testεd, oleic acid was the most effective for various NSAIDs. Based on the daily dose, lipophilicity, and the skin permeation ratε achieved in this study, ketoprofen and ketorolac seem to be the most promising drug candidates for transdermal delivery systems, especially when formulated with unsaturated fatty acids, such as oleic acid.

• Korean Journal of Clinical Pharmacy
• /
• v.25 no.3
• /
• pp.145-150
• /
• 2015

Objective: Pain is very common in the elderly, so there is a high prevalence of analgesic use among this population. The purpose of this study was to assess patterns of analgesic use and evaluate factors associated with analgesic use in elderly patients. Method: The subjects of this study were patients over 65 years old hospitalized in a teaching hospital located in Chuncheon-si, Korea between January 1, 2014 and March 31, 2014. Data collection regarding analgesic prescriptions and baseline characteristics was conducted using computerized hospital database by medical information team. Logistic regression analysis was used to identify factors related to analgesic use. Results: A total of 2,394 patients were finally included. Among these patients, 700 (29.2%) took analgesics; 521 (74.4%) out of these 700 patients were received opioid analgesics and 179 (25.6%) were received only non-opioid analgesics. The most frequently prescribed opioid analgesic was pethidine (45.7%), and the most frequently prescribed non-opioid analgesic was acetaminophen (44.1%). Fracture was associated with increased odds of opioid analgesic prescriptions (OR = 2.766, 95% CI = 2.019-3.790, p < 0.001) and any analgesic prescriptions (OR = 2.394, 95% CI = 1.766-3.244, p < 0.001). Stroke or cerebral infarction was associated with decreased odds of opioid analgesic prescriptions (OR = 0.636, 95% CI = 0.471-0.858, p = 0.003). Conclusion: A significant proportion of hospitalized elderly patients use analgesics. Health care professionals should consider factors associated with analgesic use in this population to improve pain management.

• Korean Journal of Clinical Pharmacy
• /
• v.16 no.1
• /
• pp.28-33
• /
• 2006

The stability of cefditoren in three kinds of oral liquid preparations at 4 and $25^{\circ}C$ was studied for 90 days. Two tablets of 100 mg cefditoren pivoxil were mixed with 200 mL of each oral liquid syrup, which is Pebron syrup (oxolamine citrate 10 mg/mL), $Mucopect^{(R)}$ syrup (ambroxol hydrochloride 3 mg/mL) or $Tyrenol^{(R)}$ suspension (acetaminophen encapsulated 32 mg/mL). Three samples of each formulation were refrigerated $(4^{\circ}C)$ and three were stored at room temperature $(25^{\circ}C)$. At predetermined time, samples were assayed by stability-indicating HPLC method. The chromatographic analysis after deliberate degradation showed no evidence of any breakdown product likely to interfere with the chromatographic peak of the parent substance. The relation between cefditoren pivoxil concentration and peak area was linear from 10 to $150{\mu}g/mL\;(r^2=0.9998)$. The analysis method was precise, with coefficients of variation no greater than 3.6%. Cefditoren was stable in $Mucopect^{(R)}$ syrup up to 4 weeks regardless of the temperature; in $Tyrenol^{(R)}$ suspension and Pebron syrup, it was stable for at least 28 and 45 days, and 7 and 45 days at 25 and $4^{\circ}C$, respectively. The percentages of initial cefditoren concentration remaining after 90 days were $51.5{\pm}1.8\;and\;80.9{\pm}5.6%,\;61.7{\pm}7.8\;and\;70.2{\pm}7.3%,\;and\;39.9{\pm}3.2\;and\;81.4{\pm}5.5%$ in $Mucopect^{(R)}$ syrup, $Tyrenol^{(R)}$ suspension and $Pebron^{(R)}$ syrup at 25 and $4^{\circ}C$, respectively. The pH variations of all test solutions were minimal, which was within 0.5. The results indicated that the stability of cefditoren was significantly affected by liquid solutions mixed with cefditoren, and storage tempertature.

• Toxicological Research
• /
• v.31 no.1
• /
• pp.49-59
• /
• 2015

Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers ($IL-1{\alpha}$, $IL-1{\beta}$, IL-8 and $TNF-{\alpha}$) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.23 no.6
• /
• pp.501-510
• /
• 2020

Purpose: To develop a probability-based differential diagnosis for pediatric acute liver failure (PALF) based on age and socioeconomic status of the country of origin. Methods: Comprehensive literature search using PubMed, EMBASE, and SCOPUS databases was performed. Children 0-22 years of age who met PALF registry criteria were included. Articles included >10 children, and could not be a case report, review article, or editorial. No language filter was utilized, but an English abstract was required. Etiology of PALF, age of child, and country of origin was extracted from included articles. Results: 32 full text articles were reviewed in detail; 2,982 children were included. The top diagnosis of PALF in developed countries was acetaminophen toxicity (9.24%; 95% CredI 7.99-10.6), whereas in developing countries it was Hepatitis A (28.9%; 95% CredI 26.3-31.7). In developed countries, the leading diagnosis of PALF in children aged <1 year was metabolic disorder (17.2%; 95% CredI 10.3-25.5), whereas in developing countries it was unspecified infection (39.3%; CredI 27.6-51.8). In developed countries, the leading diagnosis in children aged >1 year was Non-A-B-C Hepatitis (8.18%; CredI 5.28-11.7), whereas in developing countries it was Hepatitis A (32.4%; CredI 28.6-36.3). Conclusion: The leading causes of PALF in children aged 0-22 years differ depending on the age and developmental status of their country of origin, suggesting that these factors must be considered in the evaluation of children with PALF.

• The Korean Journal of Physiology and Pharmacology
• /
• v.20 no.4
• /
• pp.379-385
• /
• 2016

TWIK-related $K^+$ channel-2 (TREK-2) and TWIK-related spinal cord $K^+$ (TRESK) channel are members of two-pore domain $K^+$ channel family. They are well expressed and help to set the resting membrane potential in sensory neurons. Modulation of TREK-2 and TRESK channels are involved in the pathogenesis of pain, and specific activators of TREK-2 and TRESK may be beneficial for the treatment of pain symptoms. However, the effect of commonly used analgesics on TREK-2 and TRESK channels are not known. Here, we investigated the effect of analgesics on TREK-2 and TRESK channels. The effects of analgesics were examined in HEK cells transfected with TREK-2 or TRESK. Amitriptyline, citalopram, escitalopram, and fluoxetine significantly inhibited TREK-2 and TRESK currents in HEK cells (p<0.05, n=10). Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2. These results show that all analgesics tested in this study inhibit TRESK activity. Further study is needed to identify the mechanisms by which the analgesics modulate TREK-2 and TRESK differently.

• Journal of Ginseng Research
• /
• v.42 no.4
• /
• pp.577-584
• /
• 2018

Background: Ginseng (Panax ginseng) is a widely used traditional herbal supplement that possesses various health-enhancing efficacies. Various ginseng products are available in market, especially in the Korean peninsula, in the form of drinks, tablets, and capsules. The different ginseng types include the traditional red ginseng extract (RGE), white ginseng, and black red ginseng extract (BRGE). Their fermented and enzyme-treated products are also available. Different treatment regimens alter the bioavailability of certain compounds present in the respective ginseng extracts. Therefore, in this study, we aimed to compare the antioxidant and immune-stimulating activities of RGE, BRGE, and fermented red ginseng extract (FRGE). Methods: We used an acetaminophen-induced oxidative stress model for investigating the reduction of oxidative stress by RGE, BRGE, and FRGE in Sprague Dawley rats. A cyclophosphamide-induced immunosuppression model was used to evaluate the immune-stimulating activities of these ginseng extracts in BALB/c mice. Results: Our results showed that most prominently, RGE (in almost all experiments) exhibited excellent antioxidant effects via increasing superoxide dismutase, catalase, and glutathione peroxidase activities in the liver and decreasing serum 8-hydroxy-2'-deoxyguanosine, aspartate aminotransferase, and lactate dehydrogenase levels compared with the groups treated with FRGE and BRGE. Moreover, RGE significantly increased the number of white blood cells, especially T and B lymphocytes, and antibody-forming cells in the spleen and thymus, and it also activated a number of immune cell subtypes. Conclusion: Taken together, these results indicate that RGE is the best supplement for consumption in everyday life for overall health-enhancing properties.