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Biomedical subjects

T L Chen

Publications and source records attributed to T L Chen.

At least 37 records · Page 2Linked to original sources

Population PK and PK/PD modelling of microencapsulated octreotide acetate in healthy subjects.

AIMS: To develop a population model that can describe the pharmacokinetic profile of microencapsulated octreotide acetate in healthy cholecystectomized subjects. To investigate the correlation between serum IGF-1 and octreotide concentration. METHODS: A population pharmacokinetic analysis was performed on octreotide data obtained following a single dose of 30 mg microencapsulated octreotide acetate intramuscularly. The relationship between serum IGF-1 concentration and octreotide concentration was effectively described by a population pharmacokinetic/pharmacodynamic model. RESULTS: The pharmacokinetic profile of octreotide was characterized by an initial peak of octreotide followed by a sustained-release of drug. Plateau concentration were sustained up to day 70, and gradually declined to below the detection limit by day 112. A one-compartment linear model was constructed which consisted of two absorption processes, characterized by KIR and KSR, rate constants for immediate-release and sustained-release, respectively, with first-order elimination (Ke; 1.05 h-1). The surface, unencapsulated drug was immediately absorbed into the central compartment with first-order absorption (KIR; 0.0312 h-1), while the microencapsulated drug was first released in a zero-order fashion into a depot before being absorbed into the central compartment with first-order absorption (KSR; 0.00469 h-1) during a period of tau (1680 h). Body weight and gender were important covariates for the apparent volume of distribution. The type of formulation was an important covariate for KIR but had no effect on KSR. An inhibitory Emax population pharmacokinetic/pharmacodynamic model could adequately describe the relationship between IGF-1 (expressed as percent baseline) and octreotide concentration. Baseline IGF-1 concentration was found to be a significant covariate for the baseline effect (E0). A relationship between GH concentration and octreotide concentration was not established. CONCLUSIONS: The pharmacokinetic profile of microencapsulated octreotide acetate was effectively described by the derived population model. The relationship between IGF-1 and drug concentration could be used to guide optimization of therapeutic octreotide dosage regimens.

Adult↗

Effects of propofol on functional activities of hepatic and extrahepatic conjugation enzyme systems.

The effect of propofol on the hepatic and extrahepatic conjugation enzyme systems was assessed in vitro using microsomal and cytosolic preparations of human liver, hamster kidney, lung and gut. The functional activities of phase-II enzymes, including uridine diphosphate-glucuronosyltransferase (UDPGT), glutathione S-transferase (GST) and N-acetyltransferase (NAT) were evaluated in the presence of various concentrations of propofol (0.05-1.0 mmol litre-1), using 1-naphthol, 1-chloro-2,4-dinitrobenzene and p-aminobenzoic acid as substrates respectively. Propofol produced concentration-dependent inhibition of UDPGT activity in human liver microsomes. Propofol did not produce significant inhibition of human hepatic GST activity at concentrations below 1.0 mmol litre-1. In contrast, NAT activity was unaffected by propofol 0.05-1.0 mmol litre-1 in human liver cytosolic preparations. In extrahepatic tissues, hamster renal and intestinal UDPGT activities were significantly inhibited by propofol at 0.25-1.0 mmol litre-1. In these tissues, GST and NAT were unaffected by propofol at 1.0 mmol litre-1. Propofol produced differential inhibition of human liver and hamster extrahepatic conjugation enzymes as a result of different substrate and tissue specificities. The potential interference of the metabolic profile of phase-II enzymes as a result of inhibition by propofol (especially of UDPGT and GST) should be considered when using propofol with other drugs for anaesthesia.

Acetyltransferases↗

Semicontinuous production of lipase by Acinetobacter radioresistens in presence of nonwoven fabric.

The effect of a hydrophobic nonwoven fabric on the lipase production by Acinetobacter radioresistens was investigated with semicontinuous culture. The fermentation medium contained n-hexadecane as the carbon source. The nonwoven fabric was made from nylon 6 and coated with an acrylic resin. Equipping the nonwoven fabric around the baffles of a 2.5-L agitated fermentor could provide a fine dispersion of n-hexadecane, thus enhancing lipase production. The improvement on lipase yield by using the nonwoven fabric was found to be comparable to that of using an emulsifier (gum arabic). Compared with the corresponding culture in the absence of nonwoven fabric, the employment of the nonwoven fabric could significantly enhance both lipase yield and volumetric productivity.

Acinetobacter↗

Topical ocular anesthetic abuse: case report.

Topical ocular anesthetic abuse is uncommon in our clinical experience. The complications associated with topical ocular anesthetic abuse included persistent corneal epithelial defect, ring-shaped stromal infiltrate, and anterior segment inflammation. This disorder can masquerade as Acanthamoeba keratitis or other infectious keratitis. We report a suspicious case of infectious keratitis unresponsive to antibiotics. The patient had an irritable manner, low pain-control threshold, and an analgesic drug abuse history. This information, along with finding a topical ocular anesthetic bottle at bedside helped alert us to possibility of drug abuse. After discontinuing use of the topical anesthetic and using lubricants, topical steroid, and a therapeutic soft contact lens, the condition improved.

Adult↗

Modulation of cytochrome P-450 dependent monooxygenases in streptozotocin-induced diabetic hamster: I. Effects of propofol on defluorination and cytochrome P-450 activities.

BACKGROUND: Diabetes mellitus could induce polymorphic alterations of metabolic activities of cytochrome P-450 dependent monooxygenases in chemical-induced diabetic animals. The purpose of this study is to define the functional impact of clinical concentrations of propofol on the metabolic activities of cytochrome P-450 in the diabetic animals. METHODS: In order to validate the effect of propofol on cytochrome P-450 activities, especially the cytochrome P-450 2E1 and its defluorination activity, we applied NADPH-generating system to measure the metabolizing activities of cytochrome P-450 isozymes of streptozotocin-induced diabetic hamsters within the microsomes preincubated with various concentrations of propofol. The extent of defluorination and activity of cytochrome P-450 2E1 were assessed by reacting the propofol-treated microsomes in NADPH-generating system with enflurane and aniline as substrates respectively. Drug metabolizing activities of cytochrome 1A1, 2B1, and 3A4 were evaluated by metabolizing specific substrates, benzo(a)pyrene, pentoxyresorufin and erythromycin, within the microsomes of diabetic hamsters preincubated with various concentrations of propofol. RESULTS: The hepatic and renal defluorination of enflurane was significantly inhibited by 0.05 and 0.10 mM propofol in the microsomes of diabetic hamster (P < 0.05). The activities of aniline hydroxylase (cytochrome 2E1), pentoxyresorufin O-dealkylase (cytochrome 2B1) and benzo(a)pyrene hydroxylase (cytochrome 1A1) were inhibited by propofol in a concentration-dependent manner from 0.05 to 0.10 mM. However, propofol showed no significant effect to the erythromycin N-demethylase (cytochrome 3A4) at its concentration of 0.05-0.10 mM in the diabetic hamsters. CONCLUSIONS: Our data demonstrated that propofol in therapeutic concentrations of 0.05 and 0.10 mM, could inhibit both liver and kidney defluorination and cytochrome P-450's activities of the diabetic hamsters in vitro of different extent. This should remind clinicians of propofol's potential drug-to-drug interactions in the diabetic patients.

Animals↗

Modulation of cytochrome P450-dependent monooxygenases in streptozotocin-induced diabetic hamster: II. Reverse role of insulin in P450 activity and defluorination.

BACKGROUND: Metabolic activities of cytochrome (cyt) P450-dependent monooxygenase could be modulated by diabetic state in experimental diabetic animals. The purpose of this study is to validate the effect of insulin on the modulation of the metabolic activity of cyt P450 and the defluorination ability to inhalational anesthetics in diabetic animals. METHODS: Diabetic state in golden Syrian hamsters was achieved by intraperitoneal injection of streptozotocin 40 mg/kg once a day for 4 days. After stabilization of diabetic state for 6 weeks, a regimen of insulin treatment given subcutaneously was carried out. Metabolic activities of cyt P450 were assessed by the reaction with benzo(a) pyrene, pentoxyresorufin, aniline and erythromycin (specific substrates). The metabolic activities of cyt 1A1, 2B1, 2E1 and 3A4 respectively in a NADPH-generating system in microsomal preparations of the diabetic hamsters were observed before and after insulin treatment, and were compared with the control group. The ability of defluorination was evaluated by measuring the free fluoride metabolites after incubating the microsomes with enflurane in diabetic and insulin-treated hamsters. Contents of cyt P450 isozymes were measured by electrophoresis and immunoblotting before and after insulin treatment. Pathological features of hepatocytes in diabetic hamsters were evaluated microscopically before and after insulin treatment. RESULTS: The defluorination of enflurane and activity of aniline hydroxylase (cyt 2E1) were successfully induced by diabetic state (P < 0.01). The pentoxyresorufin O-dealkylase (cyt 2B1) was inhibited nearly 50% in the diabetic hamster liver when compared with that of control (P < 0.01). While the activities of benzo(a)pyrene hydroxylase (cyt 1A1) and the erythromycin N-demethylase (cyt 3A4) were basically unaffected by diabetes, alterations in content of cyt P450 were parallel to the alterations in enzyme activities. Microscopically, diabetes induced vacuolization with fatty droplets in the hepatocytes. After treatment with insulin injection, the enzyme activities, protein content and pathologic features returned to the baseline similar to the control. CONCLUSIONS: Our data demonstrated that under diabetic state, metabolic activities of cyt P450 and its extent of defluorination would be polymorphically modulated. After administration of insulin, the activities of cyt P450 and defluorination of enflurane returned to baseline as the blood sugar level had been normalized. This could remind the clinicians of the importance of insulin treatment in the potential drug-to-drug interactions in the diabetic patients.

Animals↗

Bilateral endogenous Klebsiella pneumoniae endophthalmitis associated with meningitis-useful vision regained after treatment: case report.

Endogenous endophthalmitis is a rare but devastating complication of bacteremia. Klebsiella pneumoniae is reported to be the leading organism of endogenous endophthalmitis in Taiwan, and the prognosis of endogenous Klebsiella pneumoniae endophthalmitis is extremely poor. A 46-year-old male patient was hospitalized because of fever, chills, and consciousness disturbance for 1 day. Meningitis was the impression by clinical presentation and findings of cerebrospinal fluid analysis. Parenteral ceftriaxone (4 g/day) and gentamicin (180 mg/day) were given, and his consciousness gradually cleared. On hospital day 6, he complained of blurred vision in both eyes and floaters in the left eye for 1 day. After ophthalmic examination, bilateral endogenous endophthalmitis was diagnosed. After aggressive treatment with intravitreal antibiotics and trans pars plana vitrectomy, the visual outcome of both eyes was better than those of other reported cases.

Endophthalmitis↗

Study of propofol in bovine aortic endothelium: I. Inhibitory effect on bradykinin-induced intracellular calcium immobilization.

BACKGROUND: Propofol has been found to affect the intracellular calcium concentration with clinical manifestations of hypotension and bradycardia. The purpose of this study is to examine the effect of propofol on intracellular calcium immobilization in bovine aortic endothelium under the stimulation of bradykinin. METHODS: In order to validate the effect of propofol on the alteration of intracellular calcium concentration, we used the cultured bovine endothelial cells (Gm 7372a) to measure the calcium immobilization within the cells preincubated with or without propofol of clinical concentration. Using Fluo-3 staining and a fluorescence spectrophotometer (confocal microscope), intracellular calcium immobilization was demonstrated by the appearance of "hot spots" within the cytoplasm and perinuclear regions after addition of bradykinin to the cells. The changes of fluorescence density measured within these areas versus the effect of time were analyzed and compared with the cells in control group. RESULTS: After addition of bradykinin, intracellular calcium hot spots increased dramatically within seconds and reached a maximal level within 20 seconds. The concentrations of calcium gradually decreased to a constant level after about 3 min following the addition of bradykinin to the cells. With pretreatment of propofol at 0.01 mM and 37 degrees C for 30 min, the immobilization of intracellular calcium from the intracellular stores were significantly inhibited that was demonstrated by the decreased appearance of hot spots when compared with control. CONCLUSIONS: Our data demonstrated that under the stimulation of bradykinin, propofol at 0.01 mM, could inhibit intracellular calcium release from the intracellular stores in bovine aortic endothelial cells. This phenomenon might explain the possible mechanism for the clinical manifestations of hypotension and/or bradycardia associated with propofol.

Anesthetics, Intravenous↗

Perfluorodecalin condensation on posterior surface of lens capsule and corneal endothelium during vitrectomy.

BACKGROUND: High-density vitreous substitutes, including perfluorodecalin, are widely used in current vitreoretinal surgery. We report 4 cases of perfluorodecalin condensation on the posterior capsule of the lens or corneal endothelium during vitrectomy. To the best of our knowledge, no such phenomenon has ever been reported. METHODS: This study consisted of 4 patients with retinal detachment and large retinal tears. All patients were men. All of the patients underwent pars plana vitrectomy, perfluorodecalin injection, endolaser retinopexy and air-fluid exchange. Two patients received additional surgery for scleral buckling. RESULTS: Perfluorodecalin condensation was observed on the posterior surface of the lens capsule in one phakic patient and on the endothelium in three aphakic patients during vitrectomy. The condensation obscured the image of the fundus and made air-fluid exchange difficult. The condensation could be dissipated by first removing the perfluorodecalin as completely as possible, and then by lowering the intraocular pressure below the vapor pressure of perfluorodecalin. CONCLUSIONS: Perfluorodecalin condensation may occur when perfluorodecalin is not properly used. To avoid forming condensation, high-density vitreous substitutes should never be injected into eyes that are completely air-filled, prolonged air-fluid exchanges should be avoided, and the intraocular pressure should always be kept at a higher level during air-fluid exchange.

Adult↗

Effect of oxygen transfer on lipase production by Acinetobacter radioresistens.

The influence of oxygen on alkaline lipase production by Acinetobacter radioresistens was studied under two operating modes: controlled dissolved oxygen (DO) concentration and controlled aeration rate. Compared with cell growth, the lipase production depended more extensively on oxygen. The intrinsic factor determining cell growth and lipase production was oxygen transfer rate (OTR) rather than DO concentration. Improvements in OTR, either by aeration or agitation, resulted in an increase in lipase yield and/or a reduction in fermentation time. The formation of A. radioresistens lipase could be described by a mixed-growth-associated model, and the enzyme was mainly a growth-associated product. The overall productivity for the lipase, which depended more strongly on agitation than aeration, could be related with kLa. DO concentration could not be employed in this correlation, though it has been useful as a criterion for ensuring no oxygen limitation in an aerobic fermentation.

Acinetobacter↗

Hormonal regulation of the osteoblastic phenotype expression in neonatal murine calvarial cells.

Osteoblastic cell cultures from fetal rat calvariae have provided a popular model for studying the effects of dexamethasone (DEX) and 1, 25 dihydroxyvitamin D3 [1,25(OH)2D3] on gene expression but data from murine calvarial cells are scarce. Species-specific responses of rat and mouse osteoblastic cells to these hormones have been reported previously. In the present study, we investigated the effects of DEX and 1,25(OH)2D3 on expression of the osteoblastic phenotype by mouse calvarial cells. These murine osteoblast-like (MOB) cells expressed alkaline phosphatase (ALP) activity and osteocalcin and formed calcified nodules. Unlike the rat calvarial cells, ALP activities and nodule formation in MOB were inhibited by DEX. 1,25(OH)2D3 enhanced and DEX lowered the amount of osteocalcin synthesized by MOB. 1,25(OH)2D3 did not affect the number of nodules, but increased their sizes. Treating the cells for 2 days with only DEX at the beginning of the culture enhanced the effect of 1, 25(OH)2D3 on ALP. We found that in murine calvarial cells, DEX inhibits and 1,25(OH)2D3 enhances ALP activity, osteocalcin synthesis, and calcified nodule formation. This is in contrast to previous reports of rat calvarial cells where DEX is a positive and 1,25(OH)2D3 can be a negative regulator of the osteoblastic phenotype. These results suggest that profound species-specific differences exist between mice and rats in the regulation of the osteoblastic phenotype.

Alkaline Phosphatase↗

Recombinant protein composed of Pseudomonas exotoxin A, outer membrane proteins I and F as vaccine against P. aeruginosa infection.

We have constructed a chimeric protein composed of the receptor binding and membrane translocation domains of Pseudomonas exotoxin A (PE) with the outer membrane proteins I and F, together designated as PEIF. The potential of PEIF as a vaccine against Pseudomonas infection was evaluated in BALB/c mice and New Zealand white rabbits. We examined titers of anti-PE and anti-OprF antibodies, and the ability both to neutralize PE cytotoxicity and to increase opsonophagocytic uptake of Pseudomonas aeruginosa strain PAO1, serogroups 2 and 6. The results showed that PEIF can induce antibodies not only to neutralize the PE cytotoxicity but also to promote the uptake of various strains of P. aeruginosa by murine peritoneal macrophages. In a burned mouse model, PEIF afforded significant protection against infection by the homologous P. aeruginosa strain PAO1, heterologous serogroup 2, and the PE hyperproducing strain PA103. These observations thus indicate that PEIF may be used as a novel vaccine against P. aeruginosa infection.

ADP Ribose Transferases↗

Chemical constituents and biological activities of the fruit of Zanthoxylum integrifoliolum.

Through continuing studies on the chemical constituents and antiplatelet aggregation principles of the fruit of the Formosan Zanthoxylum integrifoliolum, four new compounds-including two new lignans, (+)-pinoresinol-di-3,3-dimethylallyl ether (1), and (+)-pinoresinol-3,3-dimethylallyl ether (2); zanthonitrile (3), and one new flavonoid, 3,5-diacetyltambulin (4)-and 18 known compounds were isolated from the CHCl3-soluble fraction. Their structures were elucidated on the basis of spectral data and chemical evidence. Among the isolates, including the previously reported isobutylamides, 13 compounds showed strong in vitro antiplatelet aggregation activity, with only (-)-tetrahydroberberine showing weak vasorelaxing effect in high potassium- or norepinephrine-induced contraction of rat aorta.

Animals↗

Behavioural responses of cockerels to semen collection and their influence on semen characteristics.

One-hundred-and-twenty cockerels of Strain L2 Taiwan Country chicken from the National Chung-Hsing University were tested for their behavioural responses to semen collection at 21 to 30, 34 to 43 and 57 to 66 weeks of age. At every age period, semen was collected from every cockerel 4 times within a 1-week period. 2. Cockerel performances on most semen traits, including volume, concentration, total number of sperm, ease of collection and sensitivity to massage were very consistent within each age period. 3. Males that did not respond nervously to handling or were less sensitive to massage appeared to produce less semen. However, contamination was more serious in males that responded very nervously or were very sensitive to massage. 4. Sensitivity to massage, like semen volume, is an invariant character as indicated by the high correlation between measures taken at different age periods.

Animals↗

HELLP syndrome with antepartum pulmonary edema--a case report.

A 44-year-old pregnant female with a gestation of 29 weeks suddenly developed abdominal pain, nausea, vomiting, and laboratory study showed anemia, elevated liver enzymes, and lower platelets. HELLP syndrome was diagnosed and urgent delivery was needed. In order to correct the plasma volume and platelet deficiency, 6 units of both fresh frozen plasma and platelets, were given before operation. However, acute pulmonary edema was noted in the antepartum period. After vigorous treatment, she gave birth to a male infant. The postoperative course was smooth and she and her baby were discharged eleven days later. This case reminded us once again of the importance and necessity of invasive monitoring in fluid management of these patients.

Adult↗

Rapidly resorptive exudative retinal detachment in a patient with renogenic hypertension: case report.

We present an 18-year-old woman who developed rapidly resorptive exudative retinal detachment (ERD) due to chronic renal failure and renogenic hypertension. In July 1998, the patient came to our clinic because of a 2-month-history of progressively deteriorating visual acuity. Initially examination of the fundi revealed typical hypertensive retinopathy. Two weeks later, the patient was admitted due to hypertension and consulted our ophthalmic department again. In addition to hypertensive retinopathy, the fundi showed high bullous ERD, involving the temporal retinas in both eyes. Intensive medical therapy was begun, including blood pressure control and maintenance of body fluid and electrolyte balance, resulting in almost complete regression of retinal detachment within two days. The visual acuity improved during the following 2 weeks. The clinical features and treatment response in this rare case indicate that multiple factors, including fluids overload, hypertension, and possibly renal failure, contributed to the development of ERD. Blood pressure control and the balance of fluids are important in patients with renal failure, and may help to prevent the occurrence of ERD.

Adolescent↗

Evaluation of peribulbar anesthesia in encircling scleral buckle surgery and its postoperative pain course.

BACKGROUND: Retrobulbar anesthesia is considered effective in ocular surgery but it can give rise to serious complications. We used peribulbar anesthesia with sub-Tenon's irrigation to perform encircling scleral buckling for retinal detachment, as it could reduce the complications caused by retrobulbar anesthesia. We also recorded the course of pain for 72 hours after surgery. METHODS: Thirty patients who were diagnosed with rhegmatogenous retinal detachment were treated with an encircling scleral buckle. The surgery was performed with peribulbar anesthesia with occasional sub-Tenon's irrigation. We evaluated the patient's pain with a visual analogue scale after surgery at 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours. RESULTS: In 24 cases (80%), the anesthesia was complete with the peribulbar block. Only 6 patients (20%) needed sub-Tenon's irrigation and four of them felt no pain after augmentation. Although all the surgical procedures proceeded without problem, two of the patients felt pain and were uncomfortable during the surgery. No serious complications occurred. The course of pain peaked 6 hours after surgery when 26 patients (86.7%) felt pain and 12 patients (40%) were uncomfortable (pain score > or = 5). Forty-eight hours after surgery, 9 patients (30%) still felt pain but no one felt uncomfortable. CONCLUSION: Peribulbar anesthesia can be used safely in encircling scleral buckling for retinal detachment. The postoperative pain is maximal 6 hours after surgery and becomes mild (pain score < or = 4) after 48 hours.

Adolescent↗