Background: Up to 90% of a theophylline dose is biotransformed, by interaction with one or more the variants of the cytochrome P-450 drug metabolism system. Macrolides affect the elimination of theophylline by influencing on the microsomal enzyme systems. We evaluate the effect of erythromycin and new macrolides on the serum theophylline level and clearance. Method : Subjects consisted of moderate asthmatic patients with normal renal and hepatic functions. All subjects were non-smokers and treated with oral theophylline 400 mg per day. We randomly assigned 53 patients into four groups. Each group was treated with one macrolides, the first group erythromycin(n:19, 500 mg bid), second roxithromycin (n:14. 150 mg bid), third clarithromycin (n:10, 250 mg bid) and fourth azithromycin(n:10, 250 mg bid). We measured the serum theophylline level and clearance at three intervals, at pretreatment, after the first and fourth week after receiving the following macrolides, erythromycin, roxithromycin and clarithromycin. When azithromycin was administered, the serum theophylline level was measured at pretreatment and after one week of treatment They were measured by a computerized program of Bayesian method. Results : When compared with control, erythromycin and roxithromycin-treated groups had a significantly elevated serum theophylline level and decreased clearance. However, there were no significant changes of the serum theophylline level and clearance in clarithromycin and azithromycin-treated groups. Conclusion : These results suggest that theophylline dose may need to be readjusted and have periodic drug monitoring when erythromycin or roxithromycin is administered concurrently.
The dermal papilla cells (DPCs) of hair follicles are known to secrete paracrine factors for follicular cells. Shotgun proteomic analysis was performed to compare the expression profiles of the secretomes of human DPCs and dermal fibroblasts (DFs). In this study, the proteins secreted by DPCs and matched DFs were analyzed by 1DE/LTQ FTICR MS/MS, semi-quantitatively determined using emPAI mole percent values and then characterized using protein interaction network analysis. Among the 1,271 and 1,188 proteins identified in DFs and DPCs, respectively, 1,529 were further analyzed using the Ingenuity Pathway Analysis tool. We identified 28 DPC-specific extracellular matrix proteins including transporters (ECM1, A2M), enzymes (LOX, PON2), and peptidases (C3, C1R). The biochemically-validated DPC-specific proteins included thrombospondin 1 (THBS1), an insulin-like growth factor binding protein3 (IGFBP3), and, of particular interest, an integrin beta1 subunit (ITGB1) as a key network core protein. Using the shotgun proteomic technique and network analysis, we selected ITGB1, IGFBP3, and THBS1 as being possible hair-growth modulating protein biomarkers.
This study was performed to investigate non-invasive behavioral pain assessment of dogs after surgery, and the analgesic effects of butorphanol after intestinal anastomosis in dogs. In this study, five dogs in the Control Group were anesthetized, but did not undergo surgery. Five dogs in the Analgesic Group were undergone intestinal anastomosis and treated with butorphanol. Five dogs in the Non-analgesic Group were also undergone intestinal anastomosis without analgesic treatment. The dogs in the Analgesic Group received butorphanol (0.4 mg/kg, IM) before and immediately after operation, while dogs in Control and Non-analgesic Groups received isovolumetric doses of sterile saline. The behavior of dogs were videotaped for 400 mins after anesthesia, during which time a researcher interacted with the dog once per each 80 mins. At each interaction, the researcher recorded behavioral pain score, using University of Melbourne Pain Scale. Interactive and non-interactive behaviors were observed and quantitated by a single observer using focal continuous sampling method. Vocalizations were obtained during 400 mins after anesthesia, and duration of call, intensity, pitch, 1-4 Formant were analyzed. Surgery affected an increasing of pain score. During interactions with researcher, greeting behaviors were decreased after surgery. Differences between Analgesic group given analgesic or that given a placebo drug were readily understood using quantitative behavioral measurements and vocalization. Significant difference between Analgesic group given butorphanol or that the given placebo drug was apparent(p< 0.05).
In this study, poly lactic-co-glycolic acid (PLGA) nanoparticles (PNP) were prepared through double (w/o/w) emlusion and emulsifying solvent-evaporation technique using PLGA, which has biocompatibility and biodegradability. To maximize stability and bioavailability of the particles, chitosan-coated PLGA nanoparticles (CPNP) were prepared by charge interaction between PNP and chitosan. We demonstrated that CPNP can be utilized as a drug carrier of oral administration. The chemical structure of CPNP was analyzed by 1H-NMR and FT-IR, and all characteristic peaks appeared, confirming that it was successfully prepared. In addition, particle size and zeta potential of CPNP were analyzed using dynamic light scattering (DLS) while morphological images were obtained using transmission electron microscope (TEM). Thermal decomposition behavior of CPNP was observed through thermogravimetric analysis (TGA). In addition, the cytotoxicity of CPNP was confirmed by MTT assay at HEK293 and L929 cell lines, and it was proved that there is no toxicity confirmed by the cell viability of above 70% at all concentrations. These results suggest that the CPNP developed in this study may be used as an oral drug delivery carrier.
Objectives: Network pharmacology is a method of constructing and analyzing a drug-compound-target network to predict potential efficacy and mechanisms related to drug targets. In that large-scale analysis can be performed in a short time, it is considered a suitable tool to explore the function and role of herbal medicine. Thus, we investigated the potential functions and pathways of Chongmyunggongjin-dan (CMGJD) on Alzheimer's disease (AD) via network pharmacology analysis. Methods: Using public databases and PubChem database, compounds of CMGJD and their target genes were collected. The putative target genes of CMGJD and known target genes of AD were compared and found the correlation. Then, the network was constructed using Cytoscape 3.9.1. and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results: The result showed that total 104 compounds and 1157 related genes were gathered from CMGJD. The network consisted of 1157nodes and 10034 edges. 859 genes were interacted with AD gene set, suggesting that the effects of CMGJD are closely related to AD. Target genes of CMGJD are considerably associated with various pathways including 'Positive regulation of chemokine production', 'Cellular response to toxic substance', 'Arachidonic acid metabolic process', 'PI3K-Akt signaling pathway', 'Metabolic pathways', 'IL-17 signaling pathway' and 'Neuroactive ligand-receptor interaction'. Conclusion: Through a network pharmacological method, CMGJD was predicted to have high relevance with AD by regulating inflammation. This study could be used as a basis for effects of CMGJD on AD.
Background: 20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, has prominent benefits for the central nervous system, especially in improving learning and memory. However, its transcriptional targets in brain tissue remain unknown. Methods: In this study, we first used mass spectrometry-based drug affinity responsive target stability (DARTS) to identify the potential proteins of ginsenosides and intersected them with the transcription factor library. Second, the transcription factor PURA was confirmed as a target of PPD by biolayer interferometry (BLI) and molecular docking. Next, the effect of PPD on the transcriptional levels of target genes of PURA in brain tissues was determined by qRT-PCR. Finally, bioinformatics analysis was used to analyze the potential biological features of these target proteins. Results: The results showed three overlapping transcription factors between the proteomics of DARTS and transcription factor library. BLI analysis further showed that PPD had a higher direct interaction with PURA than parent ginsenosides. Subsequently, BLI kinetic analysis, molecular docking, and mutations in key amino acids of PURA indicated that PPD specifically bound to PURA. The results of qRT-PCR showed that PPD could increase the transcription levels of PURA target genes in brain. Finally, bioinformatics analysis showed that these target proteins were involved in learning and memory function. Conclusion: The above-mentioned findings indicate that PURA is a transcription target of PPD in brain, and PPD upregulate the transcription levels of target genes related to cognitive dysfunction by binding PURA, which could provide a chemical and biological basis for the study of treating cognitive impairment by targeting PURA.
Objectives : Nowadays the combined use of oriental herbal medicines and western biomedical medicines has been prevalent but controversial. Warfarin has been much reported to interact with some herbal medicines so that it influences prothrombin time(PT) & international normalized ratio(INR). This study was aimed to examine how much warfarin interacts with herbal medicines during treatment of stroke patients Methods : This was a retrospective case control study of 53 patients whowere treated with concomitant treatment of herbal medicines & warfarin. They were within normal limit in liver function, renal function, hematocrit, hemoglobin, and platelet count at first admission lab. We classified them into 2 classes: study group (taking herbal medicines including Panax ginseng, Angelica sinensis, Zingiber officinale, Salvia miltiorrhiza that were reported to interact with warfarin to impact PT (INR) and control group (taking other herbal medicines). We followed up PT (INR) at 5-10 days interval with AST, ALT, BUN, creatinine, hematocrit, hemoglobin, and platelet count. Results : AST, BUN, creatinine, hemoglobin, hematocrit, and platelet count were not changed significantly between first and final tests during the admission period. Only ALT decreased significantly in the control group. Neither baseline nor peak PT (INR) was significantly different between the groups. However, only warfarin dose was significantly correlated with PT and INR (r=0.810, r=0.798, p<0.01). Conclusions : It was concluded that PT(INR) was not influenced with herbal medicines and warfarin but by far dependent on warfarin dose in stroke patients restricted with normal liver function, renal function, and hematocrit, hemoglobin, and platelet count. Further prospective study is needed on larger samples to conclude that the combined therapy of herbal medicines and warfarin is safe.
The object of this study was to obtain accurate information about the co-administration effects of cardiotonic pills on the pharmacokinetics of cilostazol were observed as a process of the comprehensive and integrative medicine. Cilostazol is a synthetic anti-platelet and vasodilator agent developed for the treatment of intermittent claudication resulting from peripheral arterial disease. By increasing intracellular cyclic adenosine monophosphate (cAMP), cilostazol induces the activation of protein kinase A, which activates endothelial nitric oxide synthase. In order to evaluate the effect of a single or repeated cardiotonic pill dose on the pharmacokinetics of cilostazol, a single dose of pure_distilled water or a colloidal suspension of distilled water and cardiotonic pills were administered to the control and test groups, respectively. After 30 min, both groups were administered cilostazol. Plasma was collected 30min before administration, and 0.25, 0.5, 0.45, 1, 2, 4, 6, 8, and 24h after the end of cilostazol treatment. We then evaluated the pharmacokinetic changes observed with cilostazol between the control and test groups. No statistically significant differences were observed. These findings demonstrated that a single dose of cardiotonic pills did not affect the pharmacokinetics of cilostazol. The results obtained in this study suggest that co-administration of cardiotonic pills and cilostazol may not affect the bioavailability of cilostazol as a potential drug interaction.
Purpose: This study attempted to verify the effect of Koryo hand therapy on menstrual cramps and dysmenorrhea among college students. Method: This study performed the quasi-experimental design with nonequivalent control group and the pre and post-test design from August 28 to November 4, 2002. The subjects of this experimental study consisted of 64 college students in the nursing college of K University in D city and K college students in K city, who had more than 5.0 GRS score of menstrual cramps. Among them, 16 people belonged to the experimental group A by using Ceramic Seo Am moxa therapy, 16 to the experimental group B by using Seo Am pellet therapy, 16 to the experimental group C by using combination of Ceramic Seo Am moxa therapy and Seo Am pellet therapy and 16 to the control group. Three different kinds of methods were used three times per week for $5{\sim}6$ weeks(a total of $15{\sim}18$ times) interventions were completed. For the experimental group, A Ceramic Seo Am moxa therapy was given for 40 minutes per each treatment; for the experimental group, B Seo Am pellet therapy was given for 4 hours: for the experimental group, C combination of Ceramic Seo Am moxa therapy and Seo Am pellet therapy was given. To measure menstrual cramps, the graphic rating scale (GRS) was used and to measure dysmenorrheal, a dysmenorrhea scale (15 contents) was used, which was modified from Han &Hur's scale (13 contents). Cronbach's was 0.78 in the pre-test, 0.83 in the first post-test, 0.89 in the following post-test. Data were analyzed by one-way ANOVA, 2 test, repeated measures ANOVA, time contrast test and Sheffe test with the SPSS/Win 11.0 program. Results: ? The first hypothesis, 'Among the experimental group A by using Ceramic Seo Am moxa therapy, the experimental group B by using Seo Am pellet therapy and the experimental group C by using combination of Ceramic Seo Am moxa therapy and Seo Am pellet therapy will have different graphic rating scores of menstrual cramps', was supported (F=6.77, p=0.000, Interaction: p=0.000). ? The second hypothesis, 'Among the experimental group A by using Ceramic Seo Am moxa therapy, the experimental group B by using Seo Am pellet therapy, the experimental group C by using combination of Ceramic Seo Am moxa therapy and Seo Am pellet therapy and the control group will have a significantly different level of dysmenorrhea', was supported (F=6.88, p=0.000, Interaction: p=0.000). From the above results, it can be an effective nursing intervention to give Koryo hand therapy to college students who have menstrual cramps and dysmenorrhea. Conclusion: These findings indicate that Koryo hand therapy could be applied to improve the quality of life and to prevent drug misuse among college students who are physically, mentally and psychologically suffering from menstrual cramps and dysmenorrhea. Furthermore, Koryo hand therapy could be developed as an effective Korean alternative and complementary care in the future. and it could also provide a guideline to apply Koryo hand therapy to other pain and difficulties.
Multicellular tumor spheroids of HeLa cells have been grown in a static culture system. Samples of spheroids were exposed for 2 h to graded concentration of cis-platinum and its analogue, carboplatin, and then response assayed by survival of clonogenic cells. The purpose of present experiment is to clarify the effectiveness of these platinum compounds and to evaluate intrinsic radiosensitivity of cells using spheroids of HeLa cells as an experimental in vitro model. Variations of the drug sensitivity of monolayers as well as spheroids were also evaluated in cell-survival curves. In cis-platinum concentration-survival curve, there was a large shoulder extending as far as $Cq=3.4{\mu}M$, after which there was exponential decrease in survival curve having a Co Value of $1.2{\mu}M$ in spheroids. While the Co for the spheroids was essentially no significant change, but Cq value was larger than that of monolayers. This suggest that the effect of cis-platinum is greater En the monolayer with actively proliferaing cells than hypoxic one. In the carboplatin concentration-survival curves, the Co value of spheroids was $15.0{\mu}M$ and the ratio with the Co from monolayer cell $(32.5{\mu}M)$ was 0.40, thus indicating that the spheroids had a greater sensitivity to carboplatin than monolayers. Therefore, the effect of carboplatin is mainly on the deeper layers of spheroids acting as hypoxic cell sensitizer. The enhanced effect was obtained for monolayer cells using combined X-ray and carboplatin treatment 2 hours before irradiation. The result shown in isobologram analysis for the level of surviving fraction at 0.01 indicated that the effect of two agents was trusty supra-additive. From this experimental data, carboplatin has excited much recent interest as one of the most promising, since it is almost without nephrotoxicity and causes less gastrointestinal toxicity than cis-platinum. Interaction between carboplatin and radiation might play an important role for more effective local tumor control.
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