• Clinical and Experimental Pediatrics
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• v.52 no.4
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• pp.441-445
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• 2009

Purpose : Some patients develop side effects from theophylline even at low serum concentrations. We designed a prospective study to evaluate the side effects of theophylline. Methods : A Prospective, controlled trial study was conducted. The low-dose group received an intravenous continuous aminophylline dose of 5 mg/kg/day on the first day and subsequently 10 mg/kg/day on the following two days. The usual-dose group received 10 mg/kg/day for three days and the control group received normal saline for three days. Heart rate, respiratory rate, serum concentration of theophylline, and four adverse events (irritability, sleep disturbance, jitter, and vomiting) were checked at the time of admission and at 2, 12, 24, 48, and 72 h after the start of aminophylline infusions. Results : Nine patients out of 37 in the low-dose group and six of 21 in the usual-dose group dropped out because of uncontrolled irritability. The serum concentrations of theophylline in dropouts ($3.68{\pm}1.93$ ig/mL) and participants ($4.47{\pm}2.45$ ig/mL) were not significantly different. Irritability was a more frequent side effect in the usual-dose group at 12 h, but there was no difference between the low-dose and usual-dose groups in terms of vomiting, sleep disturbance, and jitter. Most of the severe adverse effects were observed in children below two years of age. Conclusion : Some patients dropped out regardless of the initiating aminophylline dose, especially patients under the age of two years.

• Journal of Plant Biology
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• v.21 no.1_4
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• pp.21-27
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• 1978

The effect of tannic acid on GAs and cyclic-AMP promoted amylase induction in barley aleurone layers was examined. Of a variety of adenine compounds, only cyclic-AMP and ADP showed significant activity, and these activities were promoted by addition of theophylline to the incubation medium. When aleurone layers of barley endosperm tissues were incubated with GAs in the presence of tannic acid, the amylase activity in the incubation medium was reduced. Cyclic-AMP induced amylase activity was also reduced by additiion of tannic acid. The cyclic-AMP response promoted was more sensitive to tannin inhibition than GAs response. The inhibitory effect of tannic acid shwoed reversibility by addition of higher concentration of GAs or cyclic-AMP. The tannic acid effect on GAs response was also recovered by addition of a higher concentration of cyclic-AMP. Experiment with polyacrylamide disc electrophoresis showed different isozyme patterns according to the additions in the incubation medium. Inhibitory effects of decursinol and coumarin was compared with that of tannic acid. They showed different zymogram patterns.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.16-22
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• 1993

Background: The Microbicidal and cytotoxic activities of neutrophils are to a large extent dependent on a burst of oxidative metabolism which generates superoxide anion, hydrogen peroxide, and other reactive products of oxygen. The respiratory burst of PMN is initiated by intracellular calcium mobilization that follows immune or particular stimulation and is very sensitive to modulation by c-AMP or adenosine. Despite its antagonism against adenosine, earlier study has demonstrated potent theophylline inhibition of the PMN respiratory burst at variable ranges of blood concentrations of theophylline in the healthy normal volunteers and in the septic animals pretreated or early post-treated with aminophylline (AMPH) or pentoxifylline. However it is unclear whether theophylline inhibits the superoxide generation or not in the established human sepsis caused by acute pneumonia, as taking into consideration of the fact that full activation of neutrophils have occurred within minutes after the septic insult in the animal experiments. Methods: We measured the $O_2$ generation of peripheral arterial neutrophils obtained from 11 human septic subjects caused by acute pneumonia before and 1 hour after completion of continuous AMPH infusion. Patients were identified and studied within 48 hour of admission. All subjects were administered an intravenous loading and maintenance dose of AMPH. The generation of $O_2$ was measured at a discrete time point (60 min) by the reduction of ferricytochrome c.PMA (10 ${\mu}g/ml$) was used as a stimulating agent. PMNs were isolated at a concentration of $2{\times}10^6$ cells/ml. The arterial oxygen tension, blood pressure and heart rates were also checked to evaluate the systemic effects of AMPH in the acute pneumonia. Results: The mean serum concentration of AMPH at 60 minutes was $8.8{\pm}0.6{\mu}g/ml$. Sixty minutes after AMPH infusion the generatition of $O_2$ was decreased from $0.076{\pm}0.034$ to $0.013{\pm}0.004$(OD) (p<0.05) and from $0.177{\pm}0.044$ to $0.095{\pm}0.042$(OD) (p<0.01) in the resting and stimulated PMNs respectively. $PaO_2$ was not changed after AMPH infusion. Conclusion: AMPH may compromise host defense by significant inhibition of neutrophil release of superoxide anion and it had no effect on improving $PaO_2$ in the acute pneumonia.

• Parasites, Hosts and Diseases
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• v.28 no.2
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• pp.71-78
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• 1990

To assess the role of cAMP on the growth and proliferation of Toxoplasma in HL-60 cells we tested the effect of exogenous cAMP and cAMP analogues to the co-culture system of Toxoplasma and HL-60 cells. cAMP, dbcAMP, and br-cAMP stimulated the growth of Texoplasma at a specific concentration, i.e., 100 mM, l00 mM, and 10-1 mM, respectively. There were differences in growth induction kinetics and in the rate of promotion. These results were further verified by treating the co-culture with adenylate cyclase activator, pNHppG, cAMP phosphodiesterase activators, imidasole and A23187, and cAMP phosphodiesterase inhibitors, IBMX, compound 48/80, and theophylline, separately. When the cytosolic cAMP levels increased by the reagents mentioned above, Toxoplasma in the cytoplasm of HL-60 cells stimulated to proliferate more rapidly with concentration-dependent modes compared to the control, and vice versa. It is suggested that some mechanisms are activated by the high levels of cAMP in the cytoplasm, which result in the stimulation of Toxoplasma proliferation.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.183-189
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• 1991

The present study was performed to elucidate the factors which modulate uterine prostaglandin synthesis during the implantation period in rats, by employing delayed implantation model. Administration of estradiol sharply increased uterine cAMP concentration 4 hrs later during the delayed implantation process. Concentrations of uterine PGE and $PGF_2{\alpha}$ were increased at 12 hrs after the estradiol treatment although an increase in $PGF_2{\alpha}$ was not statistically significant. The concomitant treatment of indomethacin with estradiol significantly suppressed estradiol-induced PGE and $PGF_2{\alpha}$ at 12 hrs, while uterine cAMP concentration was not suppressed. The treatment of dbcAMP without estradiol gradually increased uterine PGE and $PGF_2{\alpha}$ showing the maximum 8 hrs later, suggesting that cAMP minics estradiol effect on uterine prostaglandin synthesis during the implantation process. Furthermore, the pretreatment of theophylline, phosphodiesterase inhibitor, induced significantly greater concentrations of uterine PGE and $PGF_2{\alpha}$, compared with estradiol-only treated group. These results suggest that estradiol stimulates uterine prostaglandin synthesis and this process may be mediated by an elevation of cAMP during the delayed implantation process in rats.

• Journal of Pharmacopuncture
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• v.19 no.4
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• pp.312-318
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• 2016

Objectives: Bacterial resistant infections have become a global health challenge and threaten the society's health. Thus, an urgent need exists to find ways to combat resistant pathogens. One promising approach to overcoming bacterial resistance is the use of herbal products. Green tea catechins, the major green tea polyphenols, show antimicrobial activity against resistant pathogens. The present study aimed to investigate the effect of catechins, green tea extract, and methylxanthines in combination with gentamicin against standard and clinical isolates of Staphylococcus aureus (S. aureus) and the standard strain of Pseudomonas aeruginosa (P. aeruginosa). Methods: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) values of different agents against bacterial strains were determined. The interactions of green tea extract, epigallate catechin, epigallocatechin gallate, two types of methylxanthine, caffeine, and theophylline with gentamicin were studied in vitro by using a checkerboard method and calculating the fraction inhibitory concentration index (FICI). Results: The MICs of gentamicin against bacterial strains were in the range of $0.312-320{\mu}g/mL$. The MIC values of both types of catechins were $62.5-250{\mu}g/mL$. Green tea extract showed insufficient antibacterial activity when used alone. Methylxanthines had no intrinsic inhibitory activity against any of the bacterial strains tested. When green tea extract and catechins were combined with gentamicin, the MIC values of gentamicin against the standard strains and a clinical isolate were reduced, and synergistic activities were observed (FICI < 1). A combination of caffeine with gentamicin did not alter the MIC values of gentamicin. Conclusion: The results of the present study revealed that green tea extract and catechins potentiated the antimicrobial action of gentamicin against some clinical isolates of S. aureus and standard P. aeruginosa strains. Therefore, combinations of gentamicin with these natural compounds might be a promising approach to combat microbial resistance.

• Clinical and Experimental Reproductive Medicine
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• v.1 no.1
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• pp.49-54
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• 1974

In the present studies, effect of progesterone on the germinal vesicle break-down of the mouse oocytes cultured in the micro tube was investigated. The results obtained are as follows: As dose of progesterone in the medium rose, accordingly the break-down of the germinal vesicle was suppressed. It was found that $ED_{50}$ was 15.7 ${\mu}g$/ml, and $ED_{90}$ 60.7 ${\mu}g$/ml of progesterone. The dose suppressing the oocyte maturation was apparently higher than that on the rabbit or on the mouse embryonal development. The inhibiting effect of progesterone on the GVBD was reversible. The germinal vesicle of the oocytes were broken down immediately in the medium upon removal of the hormone. Progesterone stops meiosis at any stage upon administration, while dbe AMP or theophylline supresses only the break-down of the nuclear membrane. Recovering of the meiotic division of the oocytes once exposed to progesterone was delayed a little. The inhibiting action of progesterone was not altered by adding more pyruvate or in the presence of higher concentration of the mineral ions in the culture medium.

• Journal of Plant Biology
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• v.21 no.1_4
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• pp.13-21
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• 1978

The effect of cyclic-AMP on the induction of acid phosphatase activity in barley aleurone layers was examined. Tannic acid was used as a inhibitor. Decursinol and coumarin were also used as a comparison. Maxiumu promotion of the enzyme activity was obtained with 10-5M cyclic-AMP, but this promotion was lower than that of 10-5M GAS induced enzyme activity in incubation medium. The inhibition rate in the addition of tannic acid was shown 17% and 63% at a ratio to GAs (by weight) of 10 : 1, and 58% and 94% at a ratio of 100 : 1 treated with GAs, and cyclic-AMP, respectively. The most potentiation of 10-6M GAS effect was induced by the additiion of suboptimal concentration (10-6M) of cyclic-AMP. Additional GAs and cyclic-AMP were shown the recovery of the enzyme activity inhibited by tannic acid. The combination with cyclic-AMP and theophylline enhanced the enzyme activity, too. Any other nucleotides tested except cyclic-AMP didn't show the action. There were no differences in acid phosphatase isozyme patterns by polyacrylamide disc electrophoresis, in conjunction with the different additions but the size of bands showed great differences. Especially, the 3rd band and the 5th band group were remarkable.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.201-206
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• 2015

Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated $IC_{50}$ values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.1
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• pp.13-18
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• 2004

This study was designed to establish working range for reoportable range in own laboratory in order to cover the upper and lower limits of the range in test method. We experimented ten times during 10 days for setting of reportable range with between run for method evaluation. It is generally assumed that the analytical method produces a linear response and that the test results between those upper and lower limits are then reportable. CLIA recommends that laboratories verify the reportable range of all moderate and high complexity tests. The Clinical Laboratory Improvement Amendments(CLIA) and Laboratory Accreditation Program of the Korean Society for Laboratory Medicine states reportable range is only required for "modified" moderately complex tests. Linearity requirements have been eliminated from the CLIA regulations and from others accreditation agencies, many inspectors continue to feel that linearity studies are a part of good lab practice and should be encouraged. It is important to assess the useful reportable range of a laboratory method, i.e., the lowest and highest test results that are reliable and can be reported. Manufacturers make claims for the reportable range of their methods by stating the upper and lower limits of the range. Instrument manufacturers state an operating range and a reportable range. The commercial linearity material can be used to verify this range, if it adequately covers the stated linear interval. CLIA requirements for quality control, must demonstrate that, prior to reporting patient test results, it can obtain the performance specifications for accuracy, precision, and reportable range of patient test results, comparable to those established by the manufacturer. If applicable, the laboratory must also verify the reportable range of patient test results. The reportable range of patient test results is the range of test result values over which the laboratory can establish or verify the accuracy of the instrument, kit or test system measurement response. We need to define the usable reportable range of the method so that the experiments can be properly planned and valid data can be collected. The reportable range is usually defined as the range where the analytical response of the method is linear with respect to the concentration of the analyte being measured. In conclusion, experimental results on reportable range using concentrated control sample and zero calibrators covering from highest to lowest range were salicylate $8.8{\mu}g/dL$, phenytoin $0.67{\mu}g/dL$, phenobarbital $1.53{\mu}g/dL$, primidone $0.16{\mu}g/dL$, theophylline $0.2{\mu}g/dL$, vancomycine $1.3{\mu}g/dL$, valproic acid $3.2{\mu}g/dL$, digitoxin 0.17ng/dL, carbamazepine $0.36{\mu}g/dL$ and acetaminophen $0.7{\mu}g/dL$ at minimum level and salicylate $969.9{\mu}g/dL$, phenytoin $38.1{\mu}g/dL$, phenobarbital $60.4{\mu}g/dL$, primidone $24.57{\mu}g/dL$, theophylline $39.2{\mu}g/dL$, vancomycine $83.65{\mu}g/dL$, valproic acid $147.96{\mu}g/dL$, digitoxin 5.04ng/dL, carbamazepine $19.76{\mu}g/dL$, acetaminophen $300.92{\mu}g/dL$ at maximum level.