Felodipine is a calcium antagonist that lowers blood pressure by reducing peripheral resistance by meas of a direct, selective action on smooth muscle in arterial resistance vessels. Futhermore, it have been approved for the effective in angina pectoris and cardiac failure. The purpose of the present study was to evaluate the bioequivalence of two felodipine extended release (ER) tablets, Splendil (YuHan Corporation) and Stapin (Hana Pharmaceutial Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The felodipine release from the two felodipine formulations in vitro was tested using KP VIII Apparatus II method at pH 6.5 buffer solution. Twenty six healthy male subjects, $22.73{\pm}1.78$ years in age and $66.66{\pm}7.28\;kg$ in body weight, were divided into two groups and a radomized $2{\times}2$ cross-over study was employed. After two tablets containing 5 mg as felodipine were orally administered, blood sample was taken at predetermined time intervals and the concentrations of felodipine in serum were determined using column-switching HPLC method with UV detector. The dissolution profiles of two formulations were similar at pH 6.5 buffer solution. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the Splendil were 2.53%, 1.32% and 18.32% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance rage of log(0.86) to log(1.25) $(e.g.,\;log(0.86){\sim}log(1.20)\;and\;log(0.89){\sim}log(1.23)\;for\;AUC_t,\;C_{max},\;respectively)$. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Stapin ER tablet and Splendil ER tablet are bioequivalent.
Background: Extended endoplasmic reticulum (ER) stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. Methods: The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. Results: Compound K-induced ER stress was confirmed through increased phosphorylation of $eIF2{\alpha}$ and protein levels of GRP78/BiP, XBP-1S, and $IRE1{\alpha}$ in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular $Ca^{2+}$ chelator) or dantrolene (an RyR channel antagonist). These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12) partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor) dramatically improved the compound K-induced apoptosis. Conclusion: Cell survival and intracellular $Ca^{2+}$ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway.
In the present study, we designed and constructed new microdialysis probe in order to improve the efficacy and accuracy of microdialysis method. In addition, extracellular concentrations of GABA, glutamate, aspartate and glycine were monitored with new designed probe in the lateral portion of the ventrocaudal periaqueductal gray using unanesthetized and unrestrained rats. Furthermore, the effect of opiates on release of these amino acids, especially GABA, was analyzed by measuring their concentration in PAG dialysates following veratridine administration in the presence of systemic morphine. The results were summerized as follow : 1. The damaging rates of 1.0mm or 1.5mm window probe were 12.5% or 42.8%, respectively. In the group using 1.5mm window probe, the damaging area was extended into mesencephalic aqueduct because of microdialyzing pressure. 2. Because of the unique design of our probes with an opening facing one side, dialysis occurs in a hemisphere($600{\mu}m$ in mediolateral direction and $100{\mu}m$ in opposite side of the dialysis probe) around the opening rather than in a spherical shaped configuration which is typical of most commercially available probe designs. 3. Glutamate, taurine and glycine were present in the highest concentration in the dialysate sample obtained before treatment with veratridine, whereas, aspartate and GABA were present in the lowest concentration. 4. The concentration of all 5 amino acids increased significantly following $75{\mu}m$ veratridine perfusion into lateral ventrocaudal PAG. 5. There was no significant difference between basal and peak amino acid concentrations according to window sizes. 6. Morphine had no effect on baseline concentrations of amino acids in dialysates obtained from the lateral PAG as compared to saline treated controls. However, following veratridine treatment, morphine selectively affected GABA release in the lateral ventrocaudal PAG as compared to saline treated controls. These results suggest that GABAergic interneurons in the PAG are inhibited by opioids. Therefore, endogenous enkephalins or endorphins may directly inhibit intrinsic GABAergic intemeurons and block their tonic inhibition of PAG-NMR projection neurons. Moreover, new designed probes demonstrate improved efficiency and accuracy in collecting samples as compared to commercial types of microdialysis probes.
Purpose: To evaluate the clinical and radiological results of tibio-talo-calcaneal arthrodesis using ipsilateral distal fibula buttress which had advantages of extended operative field and release of contracted soft tissue. Materials and Methods: We retrospectively reviewed 4 postraumatic compartment syndrome, 2 residual poliomyelitis, 1 posttraumatic osteoarthritis with subtalar joint infection and 1 posttarumatic sciatic nerve palsy patients who underwent a tibio-talo-calcaneal arthrodesis from April, 1996 to March, 2002. Each of the cases was notable for a severe rigid equinovarus, persistent pus drainage of calcaneal area and paralytic foot. The mean duration of follow up was 18 months (range, $13{\sim}42$ months). The pain, function and alignment were evaluated by the modified ankle hindfoot scale of the American Orthopaedic Foot and Ankle Society (AOFAS) and patients satisfaction clinically. The radiological union were evaluated by plain AP and lateral radiographs. Results: The AOFAS score improved from 58 points (range, $47{\sim}78$) preoperatively to 82 (range, $60{\sim}89$) postoperatively. Patents satisfaction checked at 12 months after operation had favorable results (excellent and good 80%). Union rate was 100% radiographically and the mean duration of union was 12.5 weeks (range $8{\sim}22$ weeks). There was 2 cases of superficial pin tract infection and one protrusion of screw. Conclusion: Tibio-talo-calcaneal arthrodesis using ipsilateral distal fibula buttress was good modality of arthrodesis which provides wide operative field and release of contracted soft tissue in some cases of contracted foot.
In this study, the mass flow rate of the heat release rate equation, which is the major factor of the oxygen consumption method, was analyzed for the fundamental investigation of the cone-calorimeter (5 m length and 0.3 m diameter). The shapes of a completely empty inside, 3 mm pore diameter mesh and pore diameter 10 mm honeycomb with 0.76 porosity were constructed using the cone-calorimeter. To calculate the mass flow rate, four bi-directional probes and thermocouples were installed in a uniform position in the vertical direction of flow. The velocity gradient and flow perturbation were measured from the increase in Reynolds number. As the flow capacity increased, the speed gradient increased in all three shapes relative to the turbulence intensity. In addition, the deviation of extended uncertainty to the mass flow was completely low in the order of empty space, mesh (dp = 3 mm) and honeycomb (dp = 10 mm and 𝜖 = 0.76) at the 95% confidence level. The results can be used in designs to improve the flow stability of the cone calorimeter.
Journal of the Korean Academy of Child and Adolescent Psychiatry
/
v.14
no.1
/
pp.3-11
/
2003
Attention-deficit/Hyperactivity disorder(ADHD) is the most common psychiatric disorder of childhood and among the most prevalent chronic health conditions affecting school-aged children. Children with ADHD experience significant functional problems, such as school difficulties, academic underachievement, troublesome interpersonal relationships with family members and peers, and low self-esteem. The most widely used pharmacological treatments for ADHD are psychostimulants, such as methylphenidate and amphetamine salts. These medications provide clinical efficacy by increasing the availability of catecholamines, primarily dopamine, in the frontal lobe of the brain. immediate-release(IR) formulations of sychostimulants were among the most effective psychotrophic medications in the psychopharmacological treatment. However, there are some limitations of IR formulations:the short half-life and duration of efficacy, which result in the need for multiple daily dosing and the poor compliance. These limitations have led to the development of once-daily, extended-release(ER) formulations of methylphenidate and amphetamine salts. However, these ER formulations may not be as immediately helpful to ADHD children due to delayed onset of action and the acute tolerance which is the failure to sustain the efficacy with the same concentration of drug as the initial stage of medication. OROS-methylphenidate(Concerta$^{\circledR}$) given once a day produces an ascending-pattern plasma drug level generated by the osmotically released, timed drug-delivery system. These new formulations of the psychostimulants have been shown to be a useful alternative to old stimulant medications through the evidence by the clinical trials.
Journal of the Institute of Electronics Engineers of Korea CI
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v.37
no.2
/
pp.1-10
/
2000
Traditional syntax-oriented serializability notions ate considered to be not enough to handle in particular various types of transaction in terms of duration of execution. To deal with this situation, altruistic locking has attempted to reduce delay effect associated with lock release moment by use of the idea of donation. An improved form of altruism has also been deployed in extended altruistic locking in a way that scope of data to be early released is enlarged to include even data initially not intended to be donated. In this paper, we first of all investigated limitations inherent in both altruistic schemes from the perspective of alleviating starvation occasions for transactions in particular of short-lived nature. The idea of two-way donation locking(2DL) has then been experimented to see the effect of more than single donation in client-server database systems. Simulation experiments shows that 2DL outperforms the conventional two-phase locking in terms of the degree of concurrency and average transaction waiting time under the circumstances that the size of long-transaction is in between 5 and 9.
Kim, Hee-Wan;Park, Dong-Soon;Rhee, Hae-Kyung;Kim, Ung-Mo
The KIPS Transactions:PartD
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v.9D
no.2
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pp.235-242
/
2002
We propose an advanced transaction scheduling protocol for concurrency control of multilevel secure databases in wireless mobile network environment. Wireless communication is characterized by frequent spurious disconnections. So short-lived transaction must quickly access database without any delay by long-lived one. We adapted two-phase locking protocol, namely traditional syntax-oriented serializability notions, to multilevel secure databases in wireless mobile network environment. Altruistic locking, as an advanced protocol, has attempted to reduce delay effect associated with lock release moment by use of the idea of donation. An improved form of a1truism has also been deployed for extended a1truistic locking. This is in a way that scope of data to he early released is enlarged to include even data initially not intended to be donated. Our protocol is based on extended altruistic locking, but a new method, namely bi-directional donation locking for multilevel secure databases (MLBiDL), is additionally used in order to satisfy security requirements and concurrency. We showed the Simulation experiments that MLBiDL outperforms the other locking protocols in terms of the degree of throughput and average waiting time.
Purpose: This study evaluated the clinical and radiological results after reinforcement of the weakened medial joint capsule using Internal Brace (Arthrex) for treating severe hallux valgus. Materials and Methods: This study reviewed 56 cases of 50 patients that were followed-up postoperatively for at least 12 months, from September 2017 until August 2018. An extended distal chevron osteotomy combined with a distal soft-tissue release was performed by a single surgeon to treat severe hallux valgus. Internal Brace was applied in 12 cases (group A) who had weakened medial joint capsules, and capsulorrhaphy was performed in 44 cases (group B), and these two groups were compared postoperatively for the clinical and radiological results. The postoperative complications were also investigated. Results: No significant differences at 1-year follow-up on the Manchester-Oxford Foot Questionnaire and the patients' satisfaction scores were found between the two groups (p=0.905 and p=0.668, respectively). For the radiology, the changes of the values between before surgery and at 1-year follow-up according to the group showed no significant differences in the hallux valgus angle, intermetatarsal angle, and the hallux interphalangeal angle (p=0.986, p=0.516, p=0.754, respectively). Recurrence of hallux valgus was reported in two cases in group A, and in three cases in group B. Transfer metatarsalgia occurred in 4 cases in group B. Conclusion: Based on these results, we recommend the capsule reinforcing technique using Internal Brace as a successful operative option for treating a weakened medial capsule in patients with severe hallux valgus.
The Transactions of the Korea Information Processing Society
/
v.6
no.12
/
pp.3447-3455
/
1999
Database correctness is guaranteed by standard transaction scheduling schemes like two-phase locking for the context of concurrent execution environment in which short-lived ones are normally mixed with long-lived ones. Traditional syntax-oriented serializability notions are considered to be not enough to handle in particular various types of transaction in terms of duration of execution. To deal with this situation, altruistic locking has attempted to reduce delay effect associated with lock release moment by use of the idea of donation. An improved form of altruism has also been deployed in extended altruistic locking in a way that scope of data to be early released is enlarged to include even data initially not intended to be donated. In this paper, we first of all investigated limitations inherent in both altruistic schemes from the perspective of alleviating starvation occasions for transactions in particular of short-lived nature. The idea of two-way donation locking(2DL) has then been experimented to see the effect of more than single donation in distributed database systems. Simulation experiments shows that 2DL outperforms the conventional two-phase locking in terms of the degree of concurrency and average transaction waiting time under the circumstances that the size of long-transaction is in between 5 and 9.
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