The purpose of the present study was to evaluate the bioequivalence of meloxicam capsule, capsule( Boehringer Ingelheim Ltd., Korea) as a reference drug and capsule (Kukje Pharma Ind. Co., Ltd., Korea) as a test drug, according to the guidelines of Korea Food and Drug Administration(KFDA). Thirty two healthy male Korean volunteers received capsule containing meloxicam 7.5 mg in a crossover study. There was a one-week above washout period between the doses. Plasma concentrations of meloxicam were monitored for over a period of 72 hr after administration by using a high performance liquid chromatography-tandem mass spectrometer(LC-MS/MS). (the area under the plasma concentration-time curve from time zero to 72 hr), (maximum plasma drug concentration) and (time to reach ) were complied from the plasma concentration-time data. Analysis of variance(ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed and . The 90% confidence intervals of the ratio and the ratio for were log 0.8605-log 0.9847 and log 0.9765-log 1.1503, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25, recommended by KFDA. In all of these results, we concluded that capsule was bioequivalent to capsule, based on the rate and extent of absorption.
Apoptosis has been implicated in the pathogenesis of neurodegenerative diseases such as stroke and Alzheimer's disease. Apo-1/Fas gene is one of the mediators of apoptosis in stroke. MvaI polymorphism is the first polymorphic marker identified in the Apo-1/Fas gene promoter, which was typed by PCR and followed by MvaI digestion and gel electrophoresis. DNA isolated from peripheral blood collected from 91 stroke patients and 103 healthy blood donors was used for genotypes of GG, GA and AA by sequence specific primer PCR. MvaI polymorphism was examined based on Fas gene promotor region by restriction fragment length polymorphism (RFLP). The Fas-GG genotype was the least frequent in patients with stroke and healthy controls (P = 0.57). In normal Korean controls the MvaI polymorphism GA, AA and GG were 48.6%, 34.9% and 16.5%. In stroke patients were 56.2%, 29.6% and 14.2% respectively. And the allelic frequencies of MvaI*2 (G) allele were less frequent than MvaI*1 (A) allele in patients with stroke and healthy controls (P = 0.76). In normal Korean controls MvaI*1 (A) and MvaI*2 (G) alleles were 59.2% and 40.8%. In stroke patients were 57.6% and 42.4%, respectively. Our results, pending confirmation in a larger study, indicate that the Fas genotype may not appear to be a risk factor for stroke in Korean stroke patients.
A number of reports have described the protective effects of ginsenoside Rg1 (Rg1) in Alzheimer's disease (AD). However, the protective mechanisms of Rg1 in AD remain elusive.To investigate the potential mechanisms of Rg1 in β-amyloid peptide-treated SH-SY5Y cells, a comparative proteomic analysis was performed using stable isotope labeling with amino acids in cell culture combined with nano-LC-MS/MS.We identified a total of 1,149 proteins in three independent experiments. Forty-nine proteins were significantly altered by Rg1 after exposure of the cells to β-amyloid peptides. The protein interaction network analysis showed that these altered proteins were clustered in ribosomal proteins, mitochondria, the actin cytoskeleton, and splicing proteins. Among these proteins, mitochondrial proteins containing HSD17B10, AARS2, TOMM40, VDAC1, COX5A, and NDUFA4 were associated with mitochondrial dysfunction in the pathogenesis of AD.Our results suggest that mitochondrial proteins may be related to the protective mechanisms of Rg1 in AD.
Angiotensin converting enzyme (ACE) plays an important role in the physiology of vasculature, blood pressure and inflammation. ACE gene, known to have insertion/deletion (I/D) polymorphism, has been widely investigated in its relation with cardiovascular and neurodegenerative diseases and longevity. ACE gene polymorphism in an inflammation associated osteoarthritis (OA) patients is not known. Here we have investigated ACE gene polymorphism in 142 Korean primary knee OA patients and 135 healthy volunteers to establish any clinical correlates between ACE polymorphism and knee osteoarthritis. Clinical parameters such as disease onset age, Kellgren-Lawrence grade and Lequesne's functional index provided additional analysis of the relationship of ACE polymorphism and clinical features of OA. Early onset OA showed significantly higher allele frequency and carriage rate of I than late onset OA. Radiographically severe and functionally poor OA showed higher carriage rate of I allele than radiographically mild and functionally good OA, respectively. This study first reports ACE gene polymorphism to be a risk factor for early onset, severe form primary knee OA.
An accurate and selective high-performance liquid chromatography with ultraviolet detector (HPLC-UV) method was developed for quantification of alibendol in human plasma. The sample was prepared by one-step liquid-liquid extraction (LLE) using ethyl acetate from plasma. The chromatographic retention times of alibendol and carvedilol (the internal standard; IS) were 4.3 and 3.5 min, respectively, on a reverse phase C18 CAPCELL PAK (250 mm 4.6 mm I.D., 5 μm) column. The isocratic mobile phase consisted of acetonitrile-10 mM sodium phosphate (45:55, v/v; adjusted to pH 3.0 with phosphoric acid). The lower limit of quantitation (LLOQ) was 0.3 μg/mL and no interferences were detected in chromatograms. The developed HPLC method was validated by evaluating its inter- and intra-day precisions and accuracies for a linear concentration range of 0.3 and 20.0 μg/mL. Stability testing showed that alibendol was stable in human plasma during sample processing and storage. The proposed method was successfully applied to the pharmacokinetic study of the single-dose oral administration of 100 mg alibendol tablet in healthy Korean male volunteers. The Cmax, T1/2 and AUC0-t of alibendol were 5.82 ± 1.40 μg/mL, 1.47 ± 0.43 h, 10.62 ± 2.40 μg·h/mL, respectively. Keywords: Alibendol, HPLC-UV, liquid-liquid extraction, human plasma, pharmacokinetic study.
Tissue inhibitors of metalloproteinases (TIMPs) are involved in synaptic plasticity, neuronal cell differentiation and neuroprotection in the central nervous system. To investigate whether TIMP4 polymorphisms are associated with schizophrenia and autism spectrum disorders (ASDs), 480 patients (schizophrenia, n=287; ASDs, n=193) and 296 controls were enrolled. Clinical symptoms of schizophrenia and ASDs were assessed using the operation criteria checklist for psychotic illness (OPCRIT) and Childhood Autism Rating Scale (CARS), respectively. One promoter single nucleotide polymorphism (SNP; rs3755724, -55C/T) and one exonic SNP (rs17035945, 3'-untranslated region) were selected. SNPStats and SNPAnalyzer Pro programs were used to calculate odds ratios. Multiple logistic regression models were performed to analyze the genetic data. Based on the results, these two SNPs were not associated with schizophrenia and ASD. In the analysis of clinical features of schizophrenia, rs3755724 was nominally associated with schizophrenia with poor concentration (P=0.044 in the codominant2 model, P=0.041 in the log-additive model and P=0.043 in allele frequency). These results suggest that TIMP4 is not associated with the development of schizophrenia and ASD in the population studied.
The potential therapeutic action of shikonin in an experimental model of rheumatoid arthritis (RA) was investigated. As a RA animal model, DBA/1J mice were immunized two times with type II collagen. After the second collagen immunization, mice were orally administered shikonin (2 mg/kg) once a day for 35 days, and the incidence, clinical score, bone mineral density (BMD), bone mineral content (BMC) and joint histopathology were evaluated. BMD in the proximal regions of the tibia largely increased in the shikonin treatment group compared with the control group. We also examined the effect of shikonin on inflammatory cytokines and cartilage protection. Shikonin treatment significantly reduced the incidence and severity of collagen-induced arthritis (CIA), markedly abrogating joint swelling and cartilage destruction. Shikonin also significantly inhibited the production of matrix metalloproteinase (MMP)-1 and up-regulated tissue inhibitors of metalloproteinase (TIMP)-1 in mice with CIA. In conclusion, shikonin exerted therapeutic effects through regulation of MMP/TIMP; these results suggest that shikonin is an outstanding candidate as a cartilage protective medicine for RA.
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