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Biomedical subjects

T L Chen

Publications and source records attributed to T L Chen.

At least 91 records · Page 5Linked to original sources

Targeted disruption of the Dictyostelium myosin essential light chain gene produces cells defective in cytokinesis and morphogenesis.

We have previously demonstrated that the myosin essential light chain (ELC) is required for myosin function in a Dictyostelium cell line, 7-11, in which the expression of ELC was inhibited by antisense RNA overexpression. We have now disrupted the gene encoding the ELC (mlcE) in Dictyostelium by gene targeting. The mlcE- mutants provide a clean genetic background for phenotypic analysis and biochemical characterization by removing complications arising from the residual ELC present in 7-11 cells, as well as the possibility of mutations due to insertion of the antisense construct at multiple sites in the genome. The mlcE- mutants, when grown in suspension, exhibited the typical multinucleate phenotype observed in both myosin heavy chain mutants and 7-11 cells. This phenotype was rescued by introducing a construct that expressed the wild-type Dictyostelium ELC cDNA. Myosin purified from the mlcE- cells exhibited significant calcium ATPase activity, but the actin-activated ATPase activity was greatly reduced. The results obtained from the mlcE- mutants strengthen our previous conclusion based on the antisense cell line 7-11 that ELC is critical for myosin function. The proper localization of myosin in mlcE- cells suggests that its phenotypic defects primarily arise from defective contractile function of myosin rather than its mislocalization. The enzymatic defect of myosin in mlcE- cells also suggests a possible mechanism for the observed chemotactic defect of mlcE- cells. We have shown that while mlcE- cells were able to respond to chemoattractant with proper directionality, their rate of movement was reduced. During chemotaxis, proper directionality toward chemoattractant may depend primarily on proper localization of myosin, while efficient motility requires contractile function. In addition, we have analyzed the morphogenetic events during the development of mlcE- cells using lacZ reporter constructs expressed from cell type specific promoters. By analyzing the morphogenetic patterns of the two major cell types arising during Dictyostelium development, prespore and prestalk cells, we have shown that the localization of prespore cells is more susceptible to the loss of ELC than prestalk cells, although localization of both cell types is abnormal when developed in chimeras formed by mixing equal numbers of wild-type and mutant cells. These results suggest that the morphogenetic events during Dictyostelium development have different requirements for myosin.

Animals↗

[Analysing the contents of prostaglandins in gingival fibroblast and periodontal ligament cell by microspectrophotometer]

This investigation analyses the contents of prostaglandin E(2)(PGE(2)),6-keto-prostaglandin F(1a)(6-k-PGF(1a)) and thromboxane B(2)(TXB(2)) in gingival fibroblast (GF) and periodontal ligament cell(PDLC) by microspectrophotometer.The results showed that the absorbance of PGE(2) in GF was 0.25+/-0.03,the absorbance of 6-k-PGF(1a) was 0.20+/-0.03,there were significant difference between PGE(2),6-k-PGF(1a) and control group.The absorbance of PGE(2),TXB(2) and 6-k-PGF(1a) and control group.The absorbance of PGE(2),TXB(2) and 6-k-PGF(1a) in PDLC each were 0.20+/-0.20,0.16+/-0.03 and 0.13+/-0.02.They were much bigger than control group(0.07+/-0.01),which indicated prostaglandins in GF and PDLC can affect guided tissue regeneration and gingivitis degree,and there were important relationship between PG(s) in GF,PDLC and periodontitis.

Journal Article↗

[The formation of experimental periodontitis of Guinea pig]

This investigation was used silk suture and high sugar to study the formation of experimental periodontitis.The results showed that the gingival index(GI) and periodontal deep(PD) of all experimental Guinea pig were increased in the first week.There were more lymphocytes and plasmacytes in gingival proper layer in the second week.The plasmacytes and macrophages in gingival proper layer were increased much more in 4th week and alveolar bone was absorbed less,and there were more osteoclasts lying in resorpted area of alveolar bone.In the 8th week,the alveolar bone were resorpted more severe.There were more osteoblasts in the resorpted alveolar bone area besides the osteoclaste.The lysosome and endoplasmic veticulum in lymphocytes were increased.The osteoclasts near resorpted alveolar bone had several nucleus,and there were more lysosome chondriosome and endoplasmic veticulum,and the osteoclasts activity were increased,which suggests that silk suture and high sugar can form experimental periodontitis to Guinea pig and the formation time of experimental periodontitis was in the 4th week later.

Journal Article↗

[Cytochrome P450-dependent monooxygenase system and anesthetics].

The cytochrome P450-dependent monooxygenases constitute the primary enzyme system responsible for the oxidative metabolism of a variety of xenobiotics and endogenous compounds including drugs, carcinogens, fatty acids and hormones. The monooxygenase system consists of multiple forms of P450 enzymes, NADPH-cytochrome reductase and phospholipids. The level sof P450s and associated monooxygenase activities are subject to be regulated by many environmental, physiological, and pathological factors. Inhalation and intravenous anesthetics are all metabolized through these biotransformation enzymes. The pharmacokinetic properties as well as the toxicity of the anesthetics are closely related to the inducing or inhibitory status of the monooxygenase isozymes. To understand the role of cytochrome P450-monooxygenases in drug metabolism is essential for us to handle the drug-to-drug interactions and adverse effects.

Anesthetics↗

Pretreatment H2 receptor antagonists that differ in P450 modulation activity: comparative effects on paclitaxel clearance rates and neutropenia.

Histamine-2 receptor antagonists (H2RAs) are principal components of the premedication regimen used to prevent major hypersensitivity reactions in patients receiving paclitaxel. Several different H2RAs, including cimetidine, ranitidine and famotidine, have been used in clinical trials of paclitaxel, as well as by clinicians in different geographic regions and hospitals primarily because of differences in the availability of the various H2RAs. However, H2RAs have highly variable cytochrome P450-modulating capabilities, and the P450 system appears to play a major role in paclitaxel metabolism and disposition. Therefore, the use of different H2RAs may result in different pharmacologic, toxicologic and antitumor profiles due to differential effects on paclitaxel metabolism. This study evaluated whether cimetidine and famotidine, which possess disparate P450-modulating capabilities, differentially affect paclitaxel clearance rates and the agent's principal toxicity, neutropenia. Women with advanced, platinum-refractory ovarian carcinoma received two courses of treatment with 135 mg/m2 paclitaxel over 24 h while participating in the National Cancer Institute's Treatment Referral Center Protocol. A crossover design was employed in which consecutive patients received either 300 mg cimetidine i.v. or 20 mg famotidine i.v. before their first course of paclitaxel and the alternate H2RA before their second course. In order to evaluate the differential effects of cimetidine and famotidine on pertinent pharmacologic and toxicologic parameters in the same individual, paclitaxel concentrations at steady-state (Css), paclitaxel clearance rates, and absolute neutrophil counts (ANCs) were obtained during both courses. Paclitaxel Css values were not significantly different in individual patients when either cimetidine or famotidine preceded paclitaxel (p = 0.16). Mean paclitaxel clearance rates were 271 and 243 ml/min per m2 following cimetidine and famotidine, respectively. These clearance rates were not significantly different in paired analysis (p = 0.30). The likelihood of subsequently requiring granulocyte-colony stimulating factor (G-CSF) for severe neutropenia during course 1 did not differ significantly between the two H2RAs (p = 0.9). Among patients who did not require G-CSF, mean percentage decreases in ANC were 87.7% and 84.2% after paclitaxel cycles preceded by cimetidine and famotidine, respectively. These measures of neutropenia did not differ significantly in paired analysis (p = 0.13). These results show that the H2RAs cimetidine and famotidine do not differentially affect the pharmacologic and toxicity profiles of paclitaxel when used in the premediation regimen to prevent major hypersensitivity reactions, and may be interchanged.

Adult↗

Comparison of antihypertensive effects of nicardipine with nitroglycerin for perioperative hypertension.

BACKGROUND: To compare the efficacy of intravenous (iv) nicardipine with nitroglycerin for the treatment for patients with perioperative hypertension. METHODS: Forty patients with perioperative hypertension randomly divided into two groups were treated with intravenous calcium entry blocker, nicardipine, or vasodilator, nitroglycerin. Haemodynamic measurements including mean arterial and pulmonary arterial pressure, central venous and pulmonary capillary wedge pressure, and cardiac output were recorded; peripheral and pulmonary vascular resistance were calculated. RESULTS: Both medications were effective in reducing blood pressure and controlling haemodynamics. During the maintenance by continuous iv infusion, nicardipine controlled hypertension more rapidly than nitroglycerin (nicardipine 10.5 +/- 2.5 min and nitroglycerin 18.7 +/- 2.8 min, p < 0.05) without significant alteration in heart rate. The total frequency of dose adjustments required to achieve therapeutic response was significantly less in the nicardipine-treated group (2.5 +/- 0.3 for nicardipine and 6.2 +/- 1.4 for nitroglycerin, p < 0.05). Incidence of hypotensive episodes during the infusion were observed in both groups [nicardipine 5% (1/20) and nitroglycerin 30% (6/20), p < 0.05]. CONCLUSIONS: Intravenous nicardipine is as effective as nitroglycerin in the treatment of perioperative hypertension. Specific advantages have been identified such as stable dose-response effect, less hypotensive and tachycardial effects during the use of iv nicardipine in treatment of hypertensive patients.

Aged↗

Phase I and pharmacological study of the novel topoisomerase I inhibitor 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) administered as a ninety-minute infusion every 3 weeks.

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11; Irinotecan), a semisynthetic analogue of camptothecin (CPT) with broad preclinical antitumor activity, has demonstrated impressive activity in phase II trials in Japan in advanced small and non-small cell lung, colorectal, cervical, and ovarian carcinomas, as well as in refractory lymphomas and leukemias. In this phase I and pharmacological study, 90-min infusions of CPT-11 were administered every 3 weeks at doses ranging from 100 to 345 mg/m2 to patients with solid malignancies. Acute, severe, and refractory vomiting, diarrhea, and/or abdominal cramps associated with flushing, warmth, and diaphoresis occurred in the immediate posttreatment period at the 240-mg/m2 dose level in several patients who were not treated with premedications. The characteristics and temporal nature of these toxicities, the prompt resolution of symptoms following treatment with diphenhydramine, and the successful use of a premedication regimen consisting of ondansetron and diphenhydramine in preventing these acute effects suggest that vasoactive substances are involved in the mediation of these acute toxicities. With the routine use of these premedications, there was no single toxicity type that limited the escalation of CPT-11 doses. Instead, a constellation of severe hematological and gastrointestinal effects precluded the repetitive administration of CPT-11 at doses above 240 mg/m2, the maximum tolerated dose and recommended phase II dose on this schedule. Major responses were observed in patients with advanced colorectal, cervical, and renal cancers. The disposition of total CPT-11 in plasma was fit by a biexponential kinetic model with renal elimination accounting for 37 +/- 4% (SE) of total drug disposition. The Cmax for the active metabolite of CPT-11, 7-ethyl-10-hydroxycamptothecin (SN-38), was achieved at 2.2 +/- 0.1 h after treatment, and mean residence times for both CPT-11 and SN-38 were long, 9.1 and 10.0 h, respectively. Compared with topotecan, another CPT analogue under development, a larger proportion of total drug exposure was accounted for by the active lactone (closed-ring) forms of CPT-11 and SN-38; areas under the time-versus concentration curve for their respective lactone were 44 and 50% of areas under the time-versus-concentration curve for total CPT-11 and SN-38. Although intermittent dosing schedules appear to be superior to single dosing schedules for CPT and some CPT analogues in preclinical tumor models, the maintenance of biologically relevant concentrations of SN-38 for relatively long durations may negate the potential pharmacological benefits of intermittent and continuous administration schedules for CPT-11.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Determination of plasma novobiocin levels by a reversed-phase high-performance liquid chromatographic assay.

A simple and specific reversed-phase high-performance liquid chromatographic (HPLC) assay for the determination of novobiocin levels in human plasma has been developed. The sample preparation was performed by deproteinization with methanol. Prednisone was used as an internal standard. Both novobiocin and prednisone were separated on a C8 column with a gradient elution of acidic water (pH 3.0)-methanol. The recovery of novobiocin from plasma was nearly complete. The linear range was 5-1000 microM in 0.5 ml of plasma with a minimum limit of determination of 2.25 fmol of novobiocin at 254 nm. The method has been implemented and validated in an ongoing clinical trial.

Chromatography, High Pressure Liquid↗

Relation between age and clearance rate of nine investigational anticancer drugs from phase I pharmacokinetic data.

Aging influences the disposition and effects of several classes of drugs. Although drug clearance rate is correlated with toxicity for many anticancer drugs, few data have been published concerning the relationship of aging and clearance of chemotherapy. This study was performed to identify any relationship between age and clearance rate for anticancer drugs in phase I trials at the Johns Hopkins Oncology Center. In a retrospective study, we examined the clinical and pharmacokinetic data for 344 adults (aged 21-77 years) who received 9 phase I drugs with linear clearance in 13 clinical trials. We sought correlations between age and clearance for each drug and for the whole group. Data available for 9 of the 13 trials were used to compare age (< 65 or > 65 years) versus dose delivered [< the maximum tolerated dose (MTD) vs > or = the MTD] or toxicity (< grade 3 vs > or = grade 3). Of 344 patients, 81 (23.5%) were > 65 years old, 34 (9.9%) were > or = 70 years old, and 5 (1.5%) were > or = 75 years old. There was no significant correlation between drug clearance and age for individual drugs or the group as a whole. There was no significant difference between patients of the older and younger age groups with regard to dose or toxicity. Although only a small number of patients aged > or = 75 years were treated, our results suggest that the elderly do not experience greater toxicity even when treated at doses comparable with those given younger patients and should not be excluded from phase I trials on the basis of age. As the population of the United States ages, more elderly patients will be candidates for chemotherapy. A more thorough examination of the relationships between age, clearance rate, and toxicity can be accomplished as active drugs enter phase II/III studies.

Adult↗

Nasopharyngeal carcinoma with brain metastasis: a case report.

We report a case of nasopharyngeal carcinoma with brain metastasis of a 69-year-old man. The patient presented with blindness and a huge mass over right upper neck. The magnetic resonance imaging (MRI) showed right nasopharyngeal tumor and metastatic lesion in bilateral occipital regions. The bony x-ray showed diffuse osteoblastic metastases. The brain lesion was pathology-proven through the computed-tomographic guidance stereotactic biopsy.

Aged↗

Seasonal fluctuation in the incidence of intracranial aneurysm rupture and its relationship to changing climatic conditions.

Seasonal and climatic variations have been linked to the occurrence of some types of cerebrovascular disease; however, the conditions that lead to intracranial aneurysm rupture are not known. The purpose of the present study was to determine whether seasonal and climatic conditions are related to intracranial aneurysm rupture. Data provided by the Connecticut Health Information Management and Exchange were analyzed for all patients with a primary diagnosis of aneurysmal subarachnoid hemorrhage (SAH) for the fiscal years 1981, 1983, 1985, 1987, 1988, and 1989. Patient records were correlated with climatic conditions for the years 1981 to 1989 obtained from the National Climatic Data Center, National Oceanic and Atmospheric Administration, National Environmental Satellite Data, and Information Service. During the time periods studied, 1487 patients with a primary diagnosis of aneurysmal SAH were treated by reporting hospitals. Seasonal variation in the incidence of aneurysmal SAH and admission clustering were observed but differed significantly between men and women. Men showed a single large peak in late fall (Roger's r = 11.5, p < 0.005), whereas women had an annual peak occurring in late spring (Roger's r = 10.3, p < 0.01). Substantial climatic change occurred during the 72 hours prior to 10 of the 14 clusters of men who were admitted (p < 0.01, Yates' corrected chi-square 7.33, df = 1). In contrast, clusters of women admitted were not related to preceding climatic change (p > 0.25, Yates' corrected chi-square 0.06, df = 1). Hospital admissions for aneurysmal SAH display seasonal fluctuation, with women showing a different seasonal pattern from men. Changing climatic conditions precede aneurysm rupture in men but not in women, which suggests that weather is causally related to aneurysm rupture in men, and that factors that lead to aneurysm rupture in women may be different from those in men. These data do not explain why weather fronts or gradients are associated with aneurysm rupture in men.

Adult↗

Difference in efficacy of the Cell Saver in coronary bypass grafting surgery and cardiac valvular reoperations.

The efficacy of the Cell Saver in reducing transfusion requirements in patients who underwent either coronary artery bypass grafting (CABG) or reoperation for valvular replacement (Redo) were prospectively studied in 112 patients. In 41 patients, the Cell Saver was used from the beginning of the surgery (group 1), and in the other patients, no blood conservation techniques were undertaken (group 2). Perioperative hematological profile, postoperative chest tube drainage and transfusion requirements were examined in all patients. More red cells could be retrieved from the Redo patients than from the CABG patients (p < 0.05) during operation. The use of the Cell Saver in CABG patients reduced the total amount of blood transfusion required (p < 0.001). However, in the Redo patients, the use of the Cell Saver did not reduce the transfusion requirements during hospitalization. Furthermore, the amount of platelet concentrates transfused in the group 1 Redo patients was greater than the group 2 Redo patients. The use of the Cell Saver did not increase the postoperative chest tube drainage in either the CABG or the Redo patients. We conclude that the Cell Saver is useful in CABG patients, as far as the reduction of transfusion requirements is concerned; however, its efficacy in reducing transfusion requirements for Redo patients is questionable.

Blood Transfusion, Autologous↗

Change of blood pressure and urine flow rate during cardiopulmonary bypass and its relation to postoperative renal function.

The relationship between the perfusion flow, the mean arterial pressure (MAP) and the urine flow rate during cardiopulmonary bypass (CPB) and the effect of oliguria developed during CPB on the postoperative renal dysfunction were studied prospectively in 69 open heart surgery patients. The MAP, the perfusion flow and the urine flow rate were monitored every five minutes during the first 45 minutes after the commencement of CPB and after the removal of the aortic cross clamp (AX). The serum creatinine (Cr), creatinine clearance (CCr) and blood urea nitrogen were measured before operation, as well as on the first, second and third postoperative days. The dosage of catecholamines and diuretics used and the duration of intubation and hospitalization in the intensive care unit were also recorded. The urine flow rate correlated with MAP much better than the perfusion flow during CPB (r = 0.4768, p < 0.0001). The urine flow rate and MAP decreased significantly after the initiation of CPB and after the release of the AX; however, oliguria developed only during the first 30 minutes of CPB. There were no differences in postoperative Cr, postoperative CCr, doses of catecholamines or diuretics, and the duration of intubation between patients with or without development of oliguria during CPB. Parameters measured during CPB could not predict CCr during the first three postoperative days. We conclude that it is MAP rather than perfusion flow which correlates with the urine flow rate during CPB. Periods of oliguria during CPB did not correlate with or help in the prediction of the development of postoperative renal dysfunction.

Blood Pressure↗

Recovery from propofol anesthesia: a quantitative electroencephalographic analysis.

Four numerical descriptors (median frequency, spectral edge frequency-95%, total power, and delta-ratio) derived from the computer-processed electroencephalogram (Neurometrics Lifescan) were analyzed for their ability to predict imminent arousal from total intravenous anesthesia with propofol. Fifteen patients undergoing minor surgical procedures without intubation were enrolled in the study. Arousal was defined as eye opening in response to verbal stimuli. During emergence from propofol, there were no significant changes among the descriptors except the delta-ratio. Significant change of delta-ratio occurred 210 seconds before patients' arousal and thereafter. An increase of delta-ratio value indicates that patients shifted from anesthetic to arousal state. It is concluded that the degree of delta-ratio change may be used for predicting patients' arousal from propofol anesthesia.

Adult↗

Induction and inhibition of cytochrome P-450-dependent monooxygenases in hamster tissues by ethanol.

The effects of ethanol on hamster hepatic and extrahepatic monooxygenases were determined in the present study. Chronic ethanol administration increased cytochrome P-450 (P-450) content and monooxygenase activities towards aniline, N-nitrosodimethylamine, and 7-ethoxyresorufin. In contrast, benzphetamine and benzo(a)pyrene oxidation rates were decreased 21-24% by ethanol. In kidney, ethanol pretreatment increased P-450 content, aniline and N-nitrosodimethylamine oxidation activities. In lung, ethanol ingestion selectively increased aniline hydroxylation without affecting other monooxygenase activities. Intestinal monooxygenase activity was refractory to ethanol induction. Immunoblotting of the microsomal proteins showed that ethanol induced a protein cross-reactive with rabbit antibody raised against human P-450 2E1 in hamster liver, kidney, and lung. Immunoblotting analysis using mouse monoclonal antibody 1-12-3 raised against scup P-450 1A1 revealed that ethanol induced an immunorelated protein in hamster liver, kidney, and lung. Induction of P-450 2E1 and 1A was not observed with intestinal protein blots. Immunoblotting analysis using mouse monoclonal antibody 2-66-3 against rat P-450 2B1 showed inhibition of an immunorelated protein in ethanol-treated hamster liver. The inhibitory effect on P-450 2B was not observed with extrahepatic tissues. These results suggest that ethanol has the ability to induce P-450s 2E1 and 1A and to inhibit P-450 2B in hamster tissues.

Animals↗

Recombinant human transforming growth factor beta 1 modulates bone remodeling in a mineralizing bone organ culture.

TGF-beta 1 increases cell proliferation and collagen synthesis in osteoblast-like cells and bone organ cultures. However, the effects of TGF-beta 1 on bone resorption remain contradictory. Therefore, the exact role that this growth factor plays in the process of bone remodeling is still not clear. We studied the effects of recombinant human TGF-beta 1 (rhTGF-beta 1) on bone formation and resorption in a mineralizing bone organ culture system. Parietal bones from 20-day-old fetal rat calvariae were cultured up to 7 days in serum-free BGJb medium. They responded to a 1 day pulse or continuous treatment of rhTGF-beta 1 with dose-dependent increases in dry weight, [3H]thymidine ([3H]TdR) incorporation, and collagen synthesis. In contrast, rhTGF-beta 1 reduced the calcium content of the bones. This is not due to increased bone resorption but rather to failure of calcium deposition. The following responses occurred at 1 nM rhTGF-beta 1. Dry weight was increased 25-50% after 6 days in culture. DNA synthesis was increased to a maximum at day 1, reaching twofold of the control level. Adding hydroxyurea at day 0 reduced [3H]TdR incorporation in rhTGF-beta 1 treated bones to 20% of the control and indomethacin abrogated the increase in [3H]TdR stimulated by rhTGF-beta 1 to the control level. Both treatments completely blocked the increase in dry weight induced by rhTGF-beta 1 at day 6. rhTGF-beta 1 stimulated collagen synthesis to reach its maximum at day 2, with a twofold increase in [3H]proline incorporation. Basal alkaline phosphatase activity fell continuously in culture, reaching 35% of day 0 level at day 6. Enzyme activity was not altered by rhTGF-beta 1. Morphologic observations by light and electron microscopy confirmed these findings. In summary, rhTGF-beta 1 altered bone remodeling by increasing organic components and decreasing calcification in a mineralizing bone organ culture system.

Alkaline Phosphatase↗

Induction of cytochrome P450-dependent monooxygenases in hamster tissues by fasting.

The effects of fasting on liver, kidney, and lung monooxygenases were studied using hamsters starved for 4 days. Fasting treatment increased microsomal cytochrome P450 content and NADPH-cytochrome P450 reductase activity in kidney and lung. The treatment caused significant increases of aniline hydroxylation, N-nitrosodimethylamine demethylation, and 7-ethoxycoumarin O-deethylation activities in the liver, kidney, and lung. Fasting caused a threefold increase of benzphetamine N-demethylation activity in lung and a 25% increase in liver and had no effect in kidney. Benzo[a]pyrene hydroxylation activities in the fasted hamster liver, kidney, and lung were higher, lower, and similar to the controls, respectively. Gel electrophoresis of tissue microsomes from control and fasted hamsters revealed that fasting enhanced the intensity of protein band(s) in the P450 molecular weight region. Immunoblotting of the microsomal proteins showed that fasting induced a protein crossreactive with rabbit antibody raised against human P450 2E1 in hamster liver, kidney, and lung. Immunoblotting analysis using mouse monoclonal antibody 2-66-3 raised against rat P450 2B1 revealed that fasting induced an immunorelated protein preferentially in hamster lung, with minimal effects on liver and kidney. Protein blots probed with mouse monoclonal antibody 1-12-3 indicated that fasting induced a protein related to P450 1A1 in hamster liver, kidney, and lung. These results demonstrate that fasting causes a variety of inductive effects on the enzyme components and catalytic activities of monooxygenase systems as well as on the P450s 2E, 2B, and 1A in the hamster tissues.

7-Alkoxycoumarin O-Dealkylase↗