• Archives of Pharmacal Research
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• v.28 no.5
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• pp.604-611
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• 2005

Polyethylene glycol (PEG) 6000-based solid dispersions (SDs), by incorporating various pharmaceutical excipients or microemulsion systems, were prepared using a fusion method, t o compare the dissolution rates and bioavailabilities in rats. The amorphous structure of the drug in SDs was also characterized by powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The ketoconazole (KT), as an antifungal agent, was selected as a model drug. The dissolution rate of KT increased when solubilizing excipients were incorporated into the PEG-based SDs. When hydrophilic and lipophilic excipients were combined and incorporated into PEG-based SDs, a remarkable enhancement of the dissolution rate was observed. The PEG-based SDs, incorporating a self microemulsifying drug delivery system (SMEDDS) or microemulsion (ME), were also useful at improving the dissolution rate by forming a microemulsion or dispersible particles within the aqueous medium. However, due to the limited solubilization capacity, these PEG-based SDs showed dissolution rates, below 50% in this study, under sink conditions. The PEG-based SD, with no pharmaceutical excipients incorporated, increased the maximum plasma concentration (C$_{max}$) and area under the plasma concentration curve (AUC$_{0-6h}$) two-fold compared to the drug only. The bioavailability was more pronounced in the cases of solubilizing and microemulsifying PEG-based SDs. The thermograms of the PEG-based SDs showed the characteristic peak of the carrier matrix around 60$^{\circ}C$, without a drug peak, indicating that the drug had changed into an amorphous structure. The diffraction pattern of the pure drug showed the drug to be highly crystalline in nature, as indicated by numerous distinctive peaks. The lack of the numerous distinctive peaks of the drug in the PEG-based SDs demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix of the amorphous structure. The utilization of oils, fatty acid and surfactant, or their mixtures, in PEG-based SD could be a useful tool to enhance the dissolution and bioavailability of poorly water-soluble drugs by forming solubilizing and microemulsifying systems when exposed to gastrointestinal fluid.

• Korean Journal of Veterinary Research
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• v.37 no.1
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• pp.119-128
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• 1997

The relaxation of gastric fundus smooth muscles is the primary physiological event which induces the receptive relaxation of monogastric animals. L-arginine/Nitric oxide(L-arg/NO) system is known to mediate the inhibitory non-adrenergic non-cholinergic(NANC) neurotransmission in various tissues including gastrointestinal smooth muscles. The longitudinal smooth muscles of porcine gastric fundus showed fast relaxation during electrical field stimulation(EFS) and rebound contraction after EFS in NANC condition. So, the purpose of present study was elucidation of the neurotrasmitters related to the NANC relaxation and explanation of the relation between NANC relaxation and L-arg/NO system. The longitdinal smooth muscles of porcine gastric fundus were hung in the organ bath and under the presence of guanethidine($5{\times}10^{-5}M$), precontraction was induced by carbachol($1{\times}10^{-6}M$). The muscle responses to EFS and drugs were isomerically recorded. The rusults were summarized as follows. 1. The longtudinal muscles of porcine gastric fundus showed frequency-dependent relaxation and rebound contraction to electrical field stimulaton(1ms, 8V, 1~16Hz, 20sec, EFS). These responses were blocked by tetrodotoxin($1{\times}10^{-6}M$). 2. The relaxation and rebound contraction of the longitudinal muscles of porcine gastric fundus to EFS were inhibited by L-NAME($2{\times}10^{-5}M$). The inhibitory effect of L-NAME was antagonized by L-arginine($1{\times}10^{-3}M$), but not by D-arginine($1{\times}10^{-3}M$). 3. Exogenous NO($NaNO_2$, $1{\times}10^{-5}{\sim}1{\times}10^{-4}M$, pH=2.0) caused concentration-dependent relaxation as EFS did. 4. Methylene Blue($2{\times}10^{-5}M$), a soluble guanylate cyclase inhibitor, inhibited the relaxation and rebound contraction of the longitudinal muscles of porcine gastric fundus induced by EFS, but N-ethlmaleimide, a adenylate cyclase inhibitor, did not. 5. 8-Br-cGMP($1{\times}10^{-6}{\sim}3{\times}10^{-6}M$), permeable cGMP analogue, induced dose-dependent relaxation. but 8-Br-cAMP($1{\times}10^{-6}{\sim}3{\times}10^{-6}M$), permeable cAMP analogue, did not. Both did not evoked rebound contraction. 6. ${\alpha}$-chymotrypsin did not affect the relaxation of the longitudinal muscles of porcine gastric fundus. 7. Reactive blue 2($1{\times}10^{-4}M$, 40min) siginificantly inhibited the rebound contraction induced by EFS and inhibited contraction caused by exogenous ATP($1{\times}10^{-4}{\sim}1{\times}10^{-3}M$). These results suggests that NANC relaxation of the longitudinal muscles of porcine gastric fundus mainly mediated by NO and the rebound contraction is related to NO and other neurotransmitters.

• Korean Journal of Poultry Science
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• v.27 no.2
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• pp.115-132
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• 2000

Eggshell strength and eggshell pigmentation are described in this paper since these are needed for quality egg production. A strong eggshell is determined by the components of the shell (cuticle, true shell and membranes) as well as the proper function of the gastrointestinal tract, the shell gland, the Kidneys and the endocrine system. When the puller reaches sexual maturity, the medullary bone must be ready for the laying hen at the peak egg shell formation. The amount of calcium in the layer diet, sources of calcium feed, the ratio of calcium and phosphorus in the layer diet, adequate levels of vitamin D and the dietary mineral (electrolyte) balance in the body fluid are important factors along with the levels of other nutrients. Biological, environmental and managerial factors such as the age of laying flock, temperature and humidity of the hen house, bird strain, disease, egg collection through transportation and others and influence the shell breakage at various stages of movement of the eggs from the producer to the consumer. The pigments present in eggshells are protoporphyrin-Ⅸ, biliverdin-Ⅸ and its zinc chelate and occasional traces of coproporphyrin-Ⅲ. However, there are several causes of changes in eggshell pigmentation such as the age of hen, disease, drugs and surface defects due to abnormal post-cuticular deposits.

• Journal of The Korean Society of Clinical Toxicology
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• v.17 no.2
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• pp.118-125
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• 2019

Purpose: Non-benzodiazepine hypnotic drugs (including zolpidem) are associated with an increased risk of suicide and suicidal ideation. Considering the wide usage of zolpidem, this drug should be considered a possible etiology for stupor or coma in any patient exposed to this drug. However, there are no reports on zolpidem blood levels in emergency department patients in Korea. We therefore reviewed the analyzed data of a toxicology laboratory at one university affiliated hospital. Methods: The sex, age, chief symptoms, suspiciousness of poisoning, and presumption of poison were analyzed from January 2018 to June 2019. The detection frequency and level of zolpidem in the patient blood were compared to the mental changes presented, which is the main consequence of zolpidem. Results: A total of 229 toxicological analyses, requested to a toxicological laboratory at one university affiliated hospital, were reviewed. Among 229 patients, the mean age was 54.3±20.7 years old with 113 women and 116 men. 8.7% of patients have psychiatric illness and 39.7% were poisoned intentionally. The chief symptoms detected were: mental change 55.0%, gastrointestinal 14.4%, cardiovascular 10.5%, focal neurological 7.4%, respiratory 3.5%, none 8.7%, and unknown 0.4%. A request for detailed reports revealed that causative poisons were specified only in 20.1% cases. Zolpidem was detected in 22.3% cases (51/229), with median blood level 1.26 mg/L (interquartile 0.1, 5.06 mg/L) and urine 0.90 mg/L (interquartile 0.11, 5.6 mg/L). Furthermore, zolpidem was more frequently detected in toxicology analysis of patients where mental change was the primary symptom, as compared to other symptoms (32.5% vs. 9.7%, p<0.01). Conclusion: This study reported the blood level of zolpidem in suspected poisoning patients admitted to the emergency department.

• Journal of Dental Anesthesia and Pain Medicine
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• v.19 no.1
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• pp.55-66
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• 2019

Background: Postoperative nausea and vomiting (PONV) frequently occurs following bimaxillary orthognathic surgeries. Compared to opioids, Nefopam is associated with lower incidences of PONV, and does not induce gastrointestinal tract injury, coagulopathy, nephrotoxicity, or fracture healing dysfunction, which are common side effects of Nonsteroidal anti-inflammatory drugs. We compared nefopam- and fentanyl-induced incidence of PONV in patients with access to patient-controlled analgesia (PCA) following bimaxillary orthognathic surgeries. Methods: Patients undergoing bimaxillary orthognathic surgeries were randomly divided into nefopam and fentanyl groups. Nefopam 120 mg or fentanyl $700{\mu}g$ was mixed with normal saline to a final volume of 120 mL. Patients were given access to nefopam or fentanyl via PCA. Postoperative pain intensity and PONV were measured at 30 minutes and 1 hour after surgery in the recovery room and at 8, 24, 48, and 72 hours after surgery in the ward. The frequency of bolus delivery was compared at each time point. Results: Eighty-nine patients were enrolled in this study, with 48 in the nefopam (N) group and 41 in the fentanyl (F) group. PONV occurred in 13 patients (27.7%) in the N group and 7 patients (17.1%) in the F group at 8 hours post-surgery (P = 0.568), and there were no significant differences between the two groups at any of the time points. VAS scores were $4.4{\pm}2.0$ and $3.7{\pm}1.9$ in the N and F groups, respectively, at 8 hours after surgery (P = 0.122), and cumulative bolus delivery was $10.7{\pm}13.7$ and $8.6{\pm}8.5$, respectively (P = 0.408). There were no significant differences in pain or bolus delivery at any of the remaining time points. Conclusion: Patients who underwent bimaxillary orthognathic surgery and were given nefopam via PCA did not experience a lower rate of PONV compared to those that received fentanyl via PCA. Furthermore, nefopam and fentanyl did not provide significantly different postoperative pain control.

• Journal of Life Science
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• v.31 no.11
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• pp.1037-1045
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• 2021

The prevalence of obesity is increasing worldwide, and since obesity is associated with dietary factors and sedentary lifestyles, it is a disease that is readily developing in the modern population. Because obesity is accompanied by serious complications such as diabetes and cardiovascular disease, prevention and treatment are important. Currently, drugs such as liraglutide and phentermine are used to treat obesity by suppressing appetite and inducing gastrointestinal motility delay. However, various side effects may occur, including thyroid cancer, cardiovascular problems, and central nervous system disorders. Therefore, to explore an obesity treatment method with relatively few side effects, a method known as "fat browning" was introduced to change white adipose tissue into brown adipose tissue to increase energy consumption. Ongoing studies are attempting to find effective natural substances to safely induce browning. Many natural substances have been identified. The induction of browning by treatment with natural substances generally involves three mechanisms: positive control of browning-inducing factors, inhibition of differentiation into white adipose tissue, and the activation of mechanisms related to browning. In this study, we describe plant extracts with known browning-inducing effects, such as strawberry, black raspberry, cinnamomum cassia, and Ecklonia stolonifera extracts. We also summarize the underlying mechanisms of action identified thus far, including the signaling pathway mediated by these extracts to induce browning. Furthermore, the effects of brown adipose tissue generated through browning on heart disease as an endocrine organ disruptor are discussed.

• Journal of Pharmacopuncture
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• v.26 no.1
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• pp.18-26
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• 2023

Objectives: Terminalia chebula, the main ingredient of Altan Arur 5, has been used for many years in traditional medicine. This medicine is more effective than other drugs and is used to treat chronic gastritis and gastrointestinal disorders such as peptic ulcers and esophageal reflux. Other ingredients of Altan Arur 5 are Punica granatum (pomegranate), tulip seeds, black balm, and excreta of Trogopterus xanthipes. The main ingredients of T. chebula are antibacterial and analgesic in traditional medicine. Despite having been used for many years and although many studies have been conducted on the beneficial effects of this medicine and its ingredients, the toxicity of Altan Arur 5 has not yet been elucidated. Therefore, we aimed to study the toxicity of Altan Arur 5 to ensure that it is safe to use. Methods: Acute and chronic toxicity of Altan Arur 5 were assessed in 10 Kunming mice and 8 Sprague-Dawley rats, respectively, in different doses. In the acute toxicity study, Altan Arur 5 was orally administered to Kunming mice in doses of 12 g/kg, 24 g/kg, and 48 g/kg for 14 days. In the chronic toxicity study, it was orally administered to Sprague-Dawley rats in doses of 1.25 g/kg, 2.5 g/kg, and 5 g/kg for 12 weeks. Results: No significant differences were observed in the relative organ weights for mice treated with Altan Arur 5 compared with those in the control group. Furthermore, no macro- or microstructural changes were noted in the organs of any group. Conclusion: Our toxicity testing revealed that the traditional medicine Altan Arur 5 has no toxic effects in vivo.

• Journal of Digestive Cancer Research
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• v.6 no.1
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• pp.25-31
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• 2018

Background: In Korea, stomach cancer is the second most common malignancy and the third leading cause of cancer-related deaths. the time of diagnosis is very important for treatment so early detection and surgery are currently considered the mainstay of treatment, when diagnosed advanced with tumor extension through the gastric wall and direct extension into other organs, with metastatic involvement. Recently, new drugs, drug combinations, and multimodal approaches have been used to treat this disease and In cancers over expressing or amplifying HER2, the combination of cisplatin-fluoropyrimidine-trastuzumab is considered to be the treatment of reference. but At present, the choice of treatment schedule for HER2-negative tumors is based on the medical institution's preferences and adverse effects profile. The aim of this study was to evaluate the effectiveness and safety of using FOLFOX regimen as a first-line therapy or a salvage therapy in the patients with HER2-negative advanced or metastatic gastric cancer. Methods: We retrospective reviewed the patient medical record from March 2012 to July 2017. This study evaluated 113 patients. Sixty-eight patients were treated with the FOLFOX regimen for the first time (first-line group) and 45 patients were treated with the FOLFOX regimen as a second (35 patients) or third (10 patients) chemotherapy (salvage group). Results: In the first-line group, the response rate was 54.9%. In the salvage therapy group, the response rate was 24.4% and The difference was statistically significant (p=0.205). The median TTP of the first-line group was 10.7 months (95% confidence interval [95% CI], 7.8-13.7 months) and that of salvage line group was 6.1 months (95% CI, 3.8-8.4 months). The median OS of the first-line group was 15.8 months (95% CI, 12.7-18.9 months) and that of the salvage therapy group was 10.2 months (95% CI, 8.2-11.9 months). drug toxicity was similar andtolerable between two groups. Conclusion: In patients with unresctable metastatic gastric cancer, after failing to respond to first-line therapy, most patients have no alternative other than second-line therapy because the disease is highly progressive. if the performance status of the patient is good enough to be eligible to treatments beyond best supportive care. FOLFOX regimen can be a considerable therapeutic option for salvage treatment.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.114-121
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• 2023

Selective cyclooxygenase (COX)-2 inhibition is a novel strategy to reduce the risk of gastrointestinal side effects caused by conventional nonsteroidal anti-inflammatory drugs. However, some selective COX-2 inhibitors have become apparent to increase the risk of severe cardiovascular disease. The aim of this study was to examine the anti-inflammatory effect of rosemary extract (RE) and confirm the safety of cardiovascular side effects. Inhibition of COX enzyme activity was assessed, and the levels of COX-2 and prostaglandin E₂ (PGE₂) and COX-1 and thromboxane B₂ (TXB₂) were evaluated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. The 40% RE group showed increased COX-2 inhibition activity in a dose-dependent manner, whereas the 50% RE group only exhibited at 100 ㎍/mL. In a cell-based study, COX-2 mRNA expression was similar in both RE groups and PGE₂ levels tended to decrease in the 40% RE group compared to the LPS group in the LPS pretreatment condition. In the LPS posttreatment condition, the COX-2 mRNA expression decreased in the 40% RE group, and PGE₂ levels were increased in the 40 and 50% RE groups. In both conditions, there was no significant difference in COX-1 and TXB₂ levels. In conclusion, 40 and 50% RE showed significant COX-2 inhibition, similar to the positive control group. It was confirmed that the inhibition of the COX-2 expression, but the effect did not affect the balance between prostacyclin and TXB₂. These results indicate that rosemary showed COX-2 inhibition activity with a low risk of cardiovascular diseases.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.1
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• pp.19-25
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• 2002

Purpose: The triple therapy with proton pump inhibitor (PPI) has been recognized as the treatment of choice in Helicobacter pylori (H. pylori) infection in adults. However, the effect of triple therapy with omeprazole, amoxicillin and clarithromycin (OAC) on eradication of H. pylori infection in children has not been established yet. This study was performed to evaluate the efficacy of OAC triple therapy and to compare the effect of one-week with two-week therapy on H. pylori eradication. Methods: From July 1998 to July 2000, 34 children with upper gastrointestinal symptoms, who underwent upper gastrointestinal endoscopy with biopsy at entry and 4 or more weeks after therapy, were enrolled in this study. H. pylori infection was assessed by CLO test and histologic examination (Hematoxylin-Eosin stain or Alcian yellow stain) with biopsy specimens. The regimen consisted of omeprazole (0.7 mg/kg/day), amoxicillin (50 mg/kg/day), and clarithromycin (25 mg/kg/day) for 1 week (n=21) or 2 weeks (n=13). Eradication of H. pylori was determined after the termination of treatment by the CLO test and histologic examination. Results: One-week treatment group consisted of 21 children (11 male, 10 female) with a mean age of $9.5{\pm}3.0$ years. Two-week group consisted of 13 children (4 male, 9 female) with a mean age of $9.9{\pm}4.0$ years. The endoscopic diagnoses included nodular gastritis in 19 cases, superficial gastritis in 7 cases, gastric ulcer in 4 cases, purpuric duodenitis in 2 cases, and normal in 2 cases. H. pylori was eradicated in 28 of total 34 children (82.4%). In 1-week group, H. pylori was eradicated in 17 of 21 children (81%). In 2-week group, H. pylori was eradicated in 11 of 13 children (84.6%). In remaining 6 cases in whom H. pylori had not been eradicated with OAC regimen, H. pylori infection persisted despite of the treatment with additional drugs such as colloidal bismuth subcitrate ($Denol^{(R)}$) and metronidazole. Conclusion: In this study, eradication rate of H. pylori with OAC regimen was 82.4%, and the triple therapy would be highly effective as primary treatment. However, there was no significant difference in the eradication rate between the 1-week and 2-week treatment group (P=0.785).