• 한국수정란이식학회지
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• 제15권1호
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• pp.85-94
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• 2000

These experiments were conducted to examine the effects of theophylline, pentoxifylline and heparin on frozen-thawed Hanwoo sperm for enhancing motility and viability of sperm. Frozen-thawed semen collected from one bull was treated in TALP(tyrode-albuminlactate-pyruvate) containing varous concentrations of theophylline and pentoxifylline. After incubated at 5% CO2 in air atmosphere for 6 hours, the motility of sperm after the treatments was characterized by CASA(computer aided semen analysis) system. When monitored notility(MOT) and curvilinear velocity(VCL), theophylline and pentoxifylline exerted their optimal action at the concentration of 30 mM and 3 mM, respectively. No difference of sperm motility was observed when the sperm was treated with both substances compared with a single treatment of each substance. Comparison was then made for evaluating the effect of theophylline and / or pentoxiophylline on the motility and viability of significant treatment effects of each substance, high MOT and VCL values were detected in sperm treated with theophylline. In the case of sperm viability examined by an eosin-nigrosin staining, however, a significant decrease was found after the combined treatment of theophylline+pentoxyphilline than after the treatment with heparin alone or no treatment(P<0.05). In conclusion, theophylline, pentoxiphylline or heparin can be used for enhancing the motional characteristics and viability of frozen thawed Hanwoo semen. Considering characteristics of these substances, theophyline may be useful in the artificial insemination system, which requires vigorous sperm motility. While, heparin supporting sperm viability in vitro can be effectively used for improving in vitro-fertilization system.

• Archives of Pharmacal Research
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• 제22권1호
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• pp.60-67
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• 1999

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by biliary obstruction when aminophylline (8 mg/kg as theophylline, i.v.) was administered. The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes and the changes in the activity of drug metabolizing enzymes, which are suggested to be involved in theophylline metabolism, were determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to 30% of the control value while AUC (area under the palsma concentration-tie curve) and (t1/2)$\beta$ were increased 1.3 fold and3.5 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to 30% of the control value in microsomes of cirrhotic rat liver. In cirrhotic rat liver, activities of aniline hydroxylase (CYP2E1 related), erythromycin-N-demethylase (CYP3A related), and methoxyresorufin-O-demethylase (CYP1A2 related), which were reported to be related with theophyline metabolism, were decreased to 67%, 53%, and 76% that of normal rat liver, respectively. From the results, it can be concluded that in cirrhotic rats induced by biliary obstruction, the total body clearance of theophylline is markedly reduced and it may be due to decreased activity of drug metabolizing enzymes in liver.

• Toxicological Research
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• 제18권2호
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• pp.129-138
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• 2002

The mouse lymphoma assay (MLA) has been recently validated as a sensitive and specific test system to determine the genotoxic potential for a chemical. The objective of this study is to evaluate the utility of MLA for detecting mutagens. Especially, to compare MLA with the in vitro chromosomal aberration test (CA), we performed MLA using the microwell method with three chemicals (hydroxyurea, theophylline and amino acid copper complex), which were reportedly positive in the CA. In cell treated with hydroxyurea, anti-neoplastic agent that blocks DNA replication, evidence of a positive response was obtained without S9 mix for 4 h and 24 h. In addition, analysis of colony size distribution at concentration that gave an elevated mutant fraction showed that hydroxyurea induced a high proportion of small type colonies, indicating that hydroxyurea-induced mutation is associated with large chromosomal deletion. Conversely, negative MLA result was obtained for theophylline, which was wed as central nervous system stimulator. Although theophylline increased the mutant frequency at concentration of 1250 $\mu\textrm{g}$/$\textrm{m}{\ell}$ with S9 mix for 4 h, a concentration-related increase in mutant frequency was not observed. The MLA result of amino acid copper complex was considered equivocal because the positive result was obtained at concentration showing 10% or less RS or RTG. Thus, among 3 CA-positive chemicals, positive MLA result was obtained for one. The other two chemicals were negative and equivocal. However MLA, which evaluates mutagenic potential of chemicals through colony formation by cell grouth, may provide a higher predictivity of carcinogenesis than CA.

• 한국균학회지
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• 제15권4호
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• pp.238-246
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• 1987

1. 검정곰팡이(Aspergillus niger)를 실험균주로 하여 동조적으로 액침배양한 결과 포자의 발아로 부터 균사의 생장, 생식기관의 성숙 및 무성포자의 형성까지를 재현시켰다. 2. 포자형성용 배지(D배지)에 cAMP를 첨가한 실험구에 있어서는 포자형성이 촉진되었고, 그 최적 농도는 $10^{-4}M$이었다. 3. 포자형성용 배지(D배지)에 첨가한 테오필린은 포자형성을 촉진하였고, 그 최적농도는 10mg/ml이었다. 4. 포자형성용 배지(D배지)에 첨가한 카페인은 포자형성을 촉진하였고, 그 최적농도는 300mg/ml이었다. 5. 포자형성용 배지(D배지)에 cAMP와 테오필린을 함께 첨가한 실험구에서는 cAMP 단독 첨가 실험구보다 포자형성 촉진효과가 더욱 강화되었다. 6. 포자형성용 배지(D배지)에 cAMP와 카페인을 함께 첨가한 실험구에서는 cAMP 단독 첨가 실험구보다 포자형성 촉진효과가 더욱 강화되었다. 7. 포자형성용 배지(D배지)에 AMP나 ATP를 첨가한 실험구에서는 포자형성 촉진효과가 거의 없었다. 8. 아세트산염 배지에 cAMP, 테오필린, 카페인을 각각 첨가한 실험구에서는 포자형성에 대해 촉진효과를 나타내었다.

• 약학회지
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• 제38권5호
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• pp.586-594
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• 1994

The general pharmacological effects of DWQ-013, a new synthetic quinolone antibacterial agent, were examined on the central nervous system in experimentral animals and the following results were obtained. Drug interaction of DWQ-013 with theophylline, fenbufen and nonsteroidal antiinflammatory drugs was also examined. DWQ-013 decreased touch escape effect on the general behavior and decreased body temperature at a concentration of 1000 mg/kg in mice. But DWQ 013 had no effect on the locomotor activity, rotarod perfomance and traction test in mice. Furthermore, DWQ-013 increased pentobarbital-induced sleeping time and affected the onset time in acetic acid-induced writhing test in mice. DWQ-013 reduced onset time and death time on strychnine-induced convulsions and death time on pentylenetetrazole-induced convulsions at a concentration of 1000 mg/kg in mice. But, the drug had no effect on the electroshock. DWQ-013 did not interact with fenbufen and any other NSAIDs but it did interact with theophylline. From these results, it could be suggested that DWQ-013 had less pharmacological effect than other quinolones on the central nervous system.

• Clinical and Experimental Pediatrics
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• 제50권3호
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• pp.284-291
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• 2007

목 적 : 테오필린은 천식의 치료제로서 부작용을 개선하기 위하여 서방형 제제가 개발 되었고 캡슐 제형과 더불어 유소아에 대한 임상적용의 편의를 위한 건조시럽 제형이 개발 되어 사용되고 있다. 저자들은 두 가지 테오필린 제형들의 효과를 비교하기 위하여 경증의 천식 환자들에게 테오필린 캡슐 제형과 건조시럽 제형을 저용량으로 투여한 후 제형에 따른 효능을 비교 분석하였다. 방 법 : 2005년 10월 1일부터 2006년 3월 31일까지 가톨릭대학교 의정부성모병원, 경희대학교 경희의료원, 인하대학교 병원, 순천향대학교 병원, 한림대학교 강동성심병원 등의 국내 5개 대학병원 소아 알레르기클리닉에 내원하여 경증 천식으로 진단받은 2-6세 사이 환자 90명을 대상으로 12주 동안 서방형 테오필린을 건조시럽 제형 투여군(n=44)과 캡슐 제형 투여군(n=46)으로 나누어 1일 2회, 4 mg/kg/회의 용량으로 경구 투여하였다. 연구자가 임상 시험 시작(0주)과 매 4주째마다 주간 및 야간 천식 증상 개선도를 평가 하였으며, 매 4주째마다 복약 순응도, 약물 복용감, 그리고 종합적인 평가로서 약제의 유용도를 평가하였다. 이중 약제의 유용도는 환자 보호자에게도 스스로 평가할 수 있게 하였다. 4주와 12주째 혈액내 테오필린 농도와 0주와 12주째 혈액내 ECP농도를 측정하였다. 결 과 : 두 군 모두에서 4주와 12주의 혈액내 테오필린 평균 농도는 $5-10{\mu}g/mL$의 치료 농도를 보였으며 4주째부터 임상시험 시작에 비해 천식 증상의 유의한 호전을 보였다. 두 군간 비교에서는 건조시럽 투여군이 캡슐 투여군보다 주간 천식 증상 점수는 4주째부터 야간 천식 증상 점수는 8주째부터 유의하게 낮은 결과를 보였다. 연구자에 의한 약제의 유용도 평가에 있어서도 건조시럽 투여군이 캡슐 투여군보다 유의하게 높은 결과를 보였으며 평가에 있어서 주관성이 강한 환자 보호자에 의한 평가는 연구자에 의한 평가 보다 4주 먼저 건조시럽 투여군이 캡슐 투여군 보다 유의하게 높게 나타났다. 건조시럽 투여군이 캡슐 투여군 보다 약물 복용감과 복약 순응도가 유의하게 높게 나타났으며 호산구에 의한 기도 염증반응 정도를 반영하는 혈액내 ECP농도는 건조시럽 투여군에서만 12주 동안 테오필린 투약 후가 투약전보다 유의하게 감소하였다. 결 론 : 저용량의 서방형 테오필린은 항염증 작용이 있는 안전하고 유용한 천식 치료제로 생각되며 건조 시럽 제형은 캡슐 제형에 비해 장기간 복약 순응도가 높아서 특히 유소아 천식환자들의 임상적용에 많은 장점이 있는 것으로 사료된다.

• Journal of Pharmaceutical Investigation
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• 제21권1호
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• pp.33-41
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• 1991

A high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of theophylline(TP) and its metabolites, 1-methyluric acid (1-MU) and 1,3-dimethyluric acid (1,3-DMU), in rat plasma and urine. An $100\;{\mu}l$ aliquot of a plasma or urine sample was mixed with $250\;{\mu}l$ of acetonitrite and vortexed. After centrifugation, $200\;{\mu}l$ (plasma) or $20\;{\mu}l$ (urine) aliquot of the supernatant was dried by $N_2$ stream and redissolved in $100\;{\mu}l$ (plasma) or $200\;{\mu}l$ (urine) of the mobile phase. A $20\;{\mu}l$ of the mobile phase solution was injected onto a $C_{18}$ reversed-phase column. The column was maintained at $45^{\circ}C$ by the aid of electric heating jacket. The mobile phase was a 3%(v/v) methanol solution in deionized water which contains sodium acetate (100 mM) and tetrabutyl ammonium hydroxide (4 mM). pH of the mobile phase was adjusted 4.5 by the addition of acetic acid. Detection limits for TP, 1-MU, and 1,3-DMU in plasma were 0.2, 0.1 and $0.1\;{\mu}/ml$, respectively and the corresponding values in urine were all $5\;{\mu}g/ml$. Inter- and intra-day variability of the assay for all compounds in the plasma samples was less than 5.5 and 3.8%, respectively. The retention times for 1-MU, 1,3-DMU, and TP were approximately 7, 8.5 and 18 min, respectively. Sample preparation procedure used in this method was simple, rapid and reproducible. Renal clearance of TP and its metabolites in rats showed plasma concentration dependency indicating renal tubular secretion and reabsorption of them.

• Journal of Pharmaceutical Investigation
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• 제22권3호
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• pp.205-210
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• 1992

In order to develop a controlled-release oral drug delivery system (DDS) of theophylline (TP), microporous membrane-coated tablets were prepared and evaluated in vitro and in vivo. Rapidly water-soluble core tablets of TP (300 mg) were prepared by wet granulation and compression technique, Then the core tablets were spray-coated with polyvinylchloride (PVC) in which micronized sucrose particles were dispersed. Effect of formula compositions of coating suspensions on the pharmaceutical characteristics such as membrane strength and dissolution was investigated in vitro. The membranes remained unbroken in pH 1.2 buffer at $37^{\circ}C$ at least for 2 hours after the disintergration test. TP was released from the coated-released tablets at a zero-order rate over 8 hours. The release at pH 1.2 and 4.0 was similar in rate but a little more rapid than that at pH 6.8. The coated tablets were administered to three healthy male volunteers and their saliva profiles of TP were compared with those from the commercial sustained release TP tablets such as Slobid and Asconthin. Saliva TP concentrations from the coated tablets were successfully sustained over 48 hours after the dosing and were comparable to those of the commercial sustained-release tablets. The membrane-coating technique is very simple and does not need any sophisticated equipments. In this respect, the membrane-coated tablets may be superior to the commercial sustained-release tablets and this technique is worth adopting by the pharmaceutical industries.

• Asian-Australasian Journal of Animal Sciences
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• 제22권5호
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• pp.626-635
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• 2009

An experiment was conducted to investigate the effect of Butylated Hydroxy Anisole (BHA), Butylated Hydroxy Toluene (BHT), Pentoxifylline (PTX), Theophylline (TPY) and Theobromine (TBR) on cold protection ability of Murrah buffalo semen at room ($22-25^{\circ}C$) and refrigerated temperature ($4-7^{\circ}C$). Each semen sample was divided into six parts of equal volume and sperm concentration; the first was kept as a control and the remaining five were treated with BHA, BHT, PTX, TPY or TBR. Sperm motility, abnormal spermatozoa, live-dead count, hypo-osmotic swelling and acrosomal integrity were studied at room and refrigerated temperature for various incubation periods viz.; 0, 4, 8, 12 and 24 h at room and 0, 12, 24, 36, 48, 60 and 72 h at refrigerated temperature. Significant improvement in sperm motility, live-dead count, hypo-osmotic swelling and acrosomal integrity were observed in BHT, PTX and TPY fortified extender at room and refrigerated temperature for various incubation periods. From the present study it could be concluded that cold protection ability of buffalo semen can be improved through the addition of BHT followed by PTX and TPY.

• 대한약리학회지
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• 제18권1호
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• pp.43-54
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• 1982

Bile formation is a complex process comprised of three separate physiologic mechanism operating at two anatomical sites. At present time, it was known that at least two processes are responsible for total canalicular secretion at the bile canaliculus. One of the processes is bile salt-dependent secretion (BSDS) hypothesis that the active transport of bile salts from plasma to bile provided a primary stimulus for bile formation: the osmotic effect of actively transported bile acid was responsible for the movement of water and ions into bile. The other process is bile salt-independent secretion (ESIS), which is unrelated to bile salt secretion at the canaliculus and which may involve the active transport of sodium. The third process for bile formation involves the biliary ductal epithelium. Secretin-stimulated bile characteristically contained bicarbonate in high concentration. Therefor, it was suggested that secretin stimulated water and bicarbonate secretion from the biliary ductules. One the other hand, it was found that a large amounts of cAMP was present in canine bile but no apparent relationship between bile salt secretion and cAMP content in dog bile. However, bile flow studies in human have demonstrated that secretin and glucagon increase bile cAMP secretion as does secretin in baboons. Secretin increases baboon bile duct mucosal cAMP levels in addition to bile CAMP levels suggesting that in that species secretin-stimulated bile flow may be cAMP mediated. It has been postulated that glucagon and theophylline which increase the bile salt-independent secretion in dogs might act through an increased in liver cAMP content. In a few studies, the possible role of cAMP on bile formation has teen tested by administration of an exogenous derivative of cAMP, dibutyryl cAMP. In the rat, DB cAMP did not modify bile flow, but injection of DB cAMP in the dog promoted an increase in the bile salt-independent secretion. Because of these contradictory results, this study was carried out to examine the relationship between cyclic nucleotides and bile flow due to various bile salts as well as secretin or theophylline. Experiments were performed in rabbits with anesthesia produced by the injection of seconal(30 mg/kg). Rabbits had the cystic duct ligated and the proximal end of the divided common duct cannulated with an appropriately sized polyethylene catheter. A similar catheter was placed into the inferior vena cava for administration of drugs. Bile was collected for determination of cyclic nucleotides and total cholate in 15 min. intervals for a few hours. The results are summerized as followings. 1) Administrations of taurocholic acid or chenodeoxycholic acid increased significantly the concentrations of cAMP and cGMP in bile of rabbits. 2) Concentration of cAMP in bile during the continuous infusion of ursodeoxycholic acid, was remarkedly increased in accordance with the increase of bile flow, while on the contrary concentration of cGMP in bile was decreased significantly. 3) Dehydrocholic acid and deoxycholic acid significantly increased bile flow, total cholate output and cyclic nucleotides in bile. 4) Only cAMP concentration in bile was significantly increased from control value by secretin, while theophylline increased cAMP as well as cGMP in rabbit bile. 5) In addition, the administration of secretin to taurocholic acid-stimulated bile flow increased cAMP while theophylline produced the increases of cAMP and cGMP in bile. 6) The administration of insulin to taurocholic acid-stimulated bile flow decreased cAMP concentration, while on the contrary cGMP was remarkedly increased in rabbit bile.